FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Cai, XM Orzell, S Suh, S Bresette, L Sorond, F Henderson, G Feske, S Chou, SH AF Cai, Xuemei Orzell, Susannah Suh, Sarah Bresette, Linda Sorond, Farzaneh Henderson, Galen Feske, Steven Chou, Sherry H. TI Prothrombin Complex Concentrate Rapidly Reverses Coagulopathy but does not Alter Mortality in Warfarin Intracerebral Hemorrhage SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Cerebrovascular disorders; Stroke; Anticoagulation; Hemostasis C1 [Cai, Xuemei] Brigham & Womens Hosp, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Cai, Xuemei; Sorond, Farzaneh; Henderson, Galen; Feske, Steven; Chou, Sherry H.] Harvard Univ, Sch Med, Boston, MA USA. [Orzell, Susannah; Suh, Sarah; Bresette, Linda; Sorond, Farzaneh; Henderson, Galen; Feske, Steven; Chou, Sherry H.] Brigham & Womens Hosp, Boston, MA 02115 USA. RI Chou, Sherry/G-5779-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201520 ER PT J AU Chou, SH Kuruppu, S Feske, SK Suh, S Orzell, S Henderson, GV Sorond, FA Du, R Smith, IA Lo, EH Ning, MM AF Chou, Sherry H. Kuruppu, Sanjaya Feske, Steven K. Suh, Sarah Orzell, Susannah Henderson, Galen V. Sorond, Farzaneh A. Du, Rose Smith, Ian A. Lo, Eng H. Ning, MingMing TI Increased Big Endothelin-1 in Human Cerebrospinal Fluid is Associated with Vasospasm and Poor 3-month Outcome Following Subarachnoid Hemorrhage SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Biomarkers; Brain; Endothelin; Vasoconstriction C1 [Chou, Sherry H.; Feske, Steven K.; Henderson, Galen V.; Sorond, Farzaneh A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Kuruppu, Sanjaya; Smith, Ian A.] Monash Univ, Melbourne, Austria. [Suh, Sarah] Brigham & Womens Hosp, Boston, MA 02115 USA. [Orzell, Susannah] Boston Univ, Brigham & Womens Hosp, Boston, MA 02215 USA. [Lo, Eng H.; Ning, MingMing] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RI Chou, Sherry/G-5779-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201229 ER PT J AU Chou, SH Elyaman, W Bradshaw, EM Secor, EA Suh, S Orent, W De Jager, PL Du, R Feske, SK Lo, EH Ning, MM AF Chou, Sherry H. Elyaman, Wassim Bradshaw, Elizabeth M. Secor, Elizabeth A. Suh, Sarah Orent, William De Jager, Philip L. Du, Rose Feske, Steven K. Lo, Eng H. Ning, MingMing TI Candidate CSF Cytokine and Chemokine Biomarkers for Vasospasm and Poor Outcome in Human Subarachnoid Hemorrhage SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Biomarkers; Brain; Chemokines; Inflammation C1 [Chou, Sherry H.; Elyaman, Wassim; Bradshaw, Elizabeth M.; Orent, William; Du, Rose; Feske, Steven K.] Brigham & Womens Hosp, Harvard Med Sch, Boston, MA 02115 USA. [Secor, Elizabeth A.] Brigham & Womens Hosp, Broad Inst, Boston, MA 02115 USA. [Suh, Sarah] Brigham & Womens Hosp, Boston, MA 02115 USA. [De Jager, Philip L.] Brigham & Womens Hosp, Harvard Med Sch, Broad Inst, Boston, MA 02115 USA. [Ning, MingMing] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. RI Chou, Sherry/G-5779-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201099 ER PT J AU Chou, SH Orzell, SC Suh, S Henderson, G Sorond, F Du, R Feske, SK Lo, EH Ning, MM AF Chou, Sherry H. Orzell, Susannah C. Suh, Sarah Henderson, Galen Sorond, Farzaneh Du, Rose Feske, Steven K. Lo, Eng H. Ning, MingMing TI Early Elevation of Plasma Plasminogen Activator Inhibitor-1 is Associated with Vasospasm following Subarachnoid Hemorrhage SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Brain; Biomarkers; Cerebrovascular disorders; Cerebrovascular circulation C1 [Chou, Sherry H.; Orzell, Susannah C.; Suh, Sarah; Henderson, Galen; Sorond, Farzaneh; Du, Rose; Feske, Steven K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Lo, Eng H.; Ning, MingMing] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RI Chou, Sherry/G-5779-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200053 ER PT J AU Cronin, CA Sheth, KN Zhao, X Messe, SR Olson, DM Hernandez, AF Bhatt, DL Schwamm, LH Smith, EE AF Cronin, Carolyn A. Sheth, Kevin N. Zhao, Xin Messe, Steven R. Olson, DaiWai M. Hernandez, Adrian F. Bhatt, Deepak L. Schwamm, Lee H. Smith, Eric E. TI Adherence to ECASS III 3-4.5 Hour Exclusion Criteria and Association with Outcome in Clinical Practice: Data from Get With The Guidelines (GWTG)-Stroke SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Thrombolysis; Stroke C1 [Cronin, Carolyn A.; Sheth, Kevin N.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Zhao, Xin] Duke Univ, Durham, NC USA. [Messe, Steven R.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Olson, DaiWai M.; Hernandez, Adrian F.] Duke Clin Rsch Inst, Durham, NC USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Smith, Eric E.] Univ Calgary, Calgary, AB, Canada. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200101 ER PT J AU Damush, T Myers, L Anderson, J Yu, Z Ofner, S Schmid, A Williams, L AF Damush, Teresa Myers, Laura Anderson, Jane Yu, Zhangsheng Ofner, Susan Schmid, Arlene Williams, Linda TI Implementation of a Secondary Stroke Prevention Program: Effect on Medication Adherence SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Prevention; Behavioral medicine; Risk factors C1 [Damush, Teresa; Williams, Linda] Indiana Univ, Sch Med, VA Stroke QUERI Cntr, Indianapolis, IN 46204 USA. [Myers, Laura] Roudebush VAMC, Indianapolis, IN USA. [Anderson, Jane] Houston VAMC, Houston, TX USA. [Yu, Zhangsheng; Ofner, Susan] Indiana Univ, Sch Med, Dept Biostat, Indianapolis, IN 46204 USA. [Schmid, Arlene] Indiana Univ, VA Stroke QUERI Cntr, Indianapolis, IN 46204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201088 ER PT J AU Dowlatshahi, D Brouwers, B Demchuk, A Hill, MD Aviv, R Ufholz, LA Wang, YJ Zhao, XQ Wang, YL Li, N Greenberg, SM Romero, JM Rosand, J Goldstein, JN Sharma, M AF Dowlatshahi, Dar Brouwers, Bart Demchuk, Andrew Hill, Michael D. Aviv, Richard Ufholz, Lee-Anne Wang, Yongjun Zhao, Xingquan Wang, Yilong Li, Na Greenberg, Steven M. Romero, Javier M. Rosand, Jonathan Goldstein, Joshua N. Sharma, Mukul CA CTA Spot Sign Collaborators TI The Predictive Ability of the CTA Spot Sign for Hematoma Expansion is Dependent on Time Since ICH Onset: A Systematic Review and Patient-level Meta-analysis SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; CT angiography; Cerebrovascular disorders C1 [Dowlatshahi, Dar; Sharma, Mukul] Univ Ottawa, Ottawa Hosp Rsch Inst, Ottawa, ON, Canada. [Brouwers, Bart; Greenberg, Steven M.; Romero, Javier M.; Rosand, Jonathan; Goldstein, Joshua N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Demchuk, Andrew; Hill, Michael D.] Univ Calgary, Calgary, AB, Canada. [Aviv, Richard] Univ Toronto, Toronto, ON, Canada. [Ufholz, Lee-Anne] Univ Ottawa, Ottawa, ON, Canada. [Wang, Yongjun; Zhao, Xingquan; Wang, Yilong; Li, Na] Capital Med Univ, Beijing Tiantan Hosp, Beijing, Peoples R China. RI Goldstein, Joshua/H-8953-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200113 ER PT J AU Du, R Zhou, J Lorenzano, S Charoenvimolphan, N Qian, BG Rost, N Wang, J Zhang, XM Wang, X Berndt, A Devan, WJ Valant, VJ Furie, KL Rosand, J Friedlander, R Paigen, B Weiss, ST AF Du, Rose Zhou, Jing Lorenzano, Svetlana Charoenvimolphan, Nareerat Qian, Baogang Rost, Natalia Wang, Jian Zhang, Xinmu Wang, Xin Berndt, Annerose Devan, William J. Valant, Valerie J. Furie, Karen L. Rosand, Jonathan Friedlander, Robert Paigen, Beverly Weiss, Scott T. TI ZBTB7C Is Associated With Severity Of Infarction In Cerebral Ischemia SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Infarct size; Genetics C1 [Du, Rose; Zhou, Jing; Charoenvimolphan, Nareerat; Qian, Baogang; Wang, Jian; Zhang, Xinmu; Wang, Xin; Weiss, Scott T.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lorenzano, Svetlana; Rost, Natalia; Devan, William J.; Valant, Valerie J.; Rosand, Jonathan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Berndt, Annerose; Friedlander, Robert] Univ Pittsburgh, Pittsburgh, PA USA. [Furie, Karen L.] Brown Univ, Providence, RI 02912 USA. [Paigen, Beverly] Jackson Lab, Bar Harbor, ME 04609 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201478 ER PT J AU Edlow, BL Wu, O Singhal, AB Chaudhry, ZA Yoo, AJ Stern, BJ Sheth, KN Kimberly, WT AF Edlow, Brian L. Wu, Ona Singhal, Aneesh B. Chaudhry, Zeshan A. Yoo, Albert J. Stern, Barney J. Sheth, Kevin N. Kimberly, W. T. TI Glyburide Reduces Cytotoxic Edema within the Cerebral Peduncles in Acute Ischemic Stroke SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Magnetic resonance imaging; Drugs C1 [Edlow, Brian L.; Wu, Ona; Singhal, Aneesh B.; Chaudhry, Zeshan A.; Yoo, Albert J.; Kimberly, W. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stern, Barney J.; Sheth, Kevin N.] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200612 ER PT J AU Esposito, E Mandeville, ET Hayakawa, K Lo, EH Singhal, AB AF Esposito, Elga Mandeville, Emiri T. Hayakawa, Kazuhide Lo, Eng H. Singhal, Aneesh B. TI Effects of Intra- and Post-Ischemic Normobaric Oxygen Therapy on Long Term Outcomes After Focal Ischemic Stroke SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Oxygen; Stroke; Infarct size; Ischemia reperfusion C1 [Esposito, Elga; Mandeville, Emiri T.; Hayakawa, Kazuhide; Lo, Eng H.; Singhal, Aneesh B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200588 ER PT J AU Falcone, GJ Biffi, A Brouwers, HB Anderson, C Battey, TW Ayres, AM Vashkevich, A Schwab, K Rost, NS Goldstein, JN Viswanathan, A Greenberg, SM Rosand, J AF Falcone, Guido J. Biffi, Alessandro Brouwers, H. B. Anderson, Christopher Battey, Thomas W. Ayres, Alison M. Vashkevich, Anastasia Schwab, Kristin Rost, Natalia S. Goldstein, Joshua N. Viswanathan, Anand Greenberg, Steven M. Rosand, Jonathan TI Determinants of Hematoma Volume Differ by Location in Intracerebral Hemorrhage SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Stroke volume; Anticoagulation C1 [Falcone, Guido J.; Biffi, Alessandro; Brouwers, H. B.; Anderson, Christopher; Battey, Thomas W.; Ayres, Alison M.; Vashkevich, Anastasia; Schwab, Kristin; Rost, Natalia S.; Goldstein, Joshua N.; Viswanathan, Anand; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Goldstein, Joshua/H-8953-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201522 ER PT J AU Falcone, GJ Biffi, A Devan, W Brouwers, HB Anderson, C Valant, V Ayres, AM Schwab, K Rost, NS Goldstein, JN Viswanathan, A Greenberg, SM Selim, M Meschia, JF Brown, DL Worral, BB Silliman, SL Tirschwell, DL Rosand, J AF Falcone, Guido J. Biffi, Alessandro Devan, William Brouwers, H. B. Anderson, Christopher Valant, Valerie Ayres, Alison M. Schwab, Kristin Rost, Natalia S. Goldstein, Joshua N. Viswanathan, Anand Greenberg, Steven M. Selim, Magdy Meschia, James F. Brown, Devin L. Worral, Bradford B. Silliman, Scott L. Tirschwell, David L. Rosand, Jonathan TI Burden of Blood Pressure-Related Alleles is Associated with Larger Hematoma Volume and Worse Outcome in Intracerebral Hemorrhage SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Genetics; Hypertension C1 [Falcone, Guido J.; Biffi, Alessandro; Devan, William; Brouwers, H. B.; Anderson, Christopher; Valant, Valerie; Ayres, Alison M.; Schwab, Kristin; Rost, Natalia S.; Goldstein, Joshua N.; Viswanathan, Anand; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Selim, Magdy] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Meschia, James F.] Mayo Clin, Jacksonville, FL 32224 USA. [Brown, Devin L.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Worral, Bradford B.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Silliman, Scott L.] Univ Florida, Coll Med, Jacksonville, FL USA. [Tirschwell, David L.] Univ Washington, Seattle, WA 98195 USA. RI Goldstein, Joshua/H-8953-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200117 ER PT J AU Fehnel, CR Ayres, A Rost, NS AF Fehnel, Corey R. Ayres, Alison Rost, Natalia S. TI Tobacco And Stroke Among Active and Prior Cocaine Users: An Avenue For Prevention. SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Risk factors; Prevention; Epidemiology; Drugs; Stroke C1 [Fehnel, Corey R.] Brown Univ, Rhode Isl Hosp, Alpert Med Sch, Providence, RI 02903 USA. [Ayres, Alison] Massachusetts Gen Hosp, J Philip Kistler Stroke Rsch Cntr, Boston, MA 02114 USA. [Rost, Natalia S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, J Philip Kistler Stroke Rsch Cntr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200519 ER PT J AU Fonarow, GC Smith, EE Zhao, X Peterson, ED Xian, Y Olson, DM Hernandez, AF Bhatt, DL Saver, JL Schwamm, LH AF Fonarow, Gregg C. Smith, Eric E. Zhao, Xin Peterson, Eric D. Xian, Ying Olson, DaiWai M. Hernandez, Adrian F. Bhatt, Deepak L. Saver, Jeffrey L. Schwamm, Lee H. TI Use of Strategies to Improve Door-to-Needle Times with Tissue Plasminogen Activator in Acute Ischemic Stroke by US Hospitals: Findings from the Target: Stroke Survey SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Thrombolysis; Quality assessment; Emergency care; Patient care C1 [Fonarow, Gregg C.; Saver, Jeffrey L.] UCLA Med Cntr, Los Angeles, CA USA. [Smith, Eric E.] Univ Calgary, Calgary, AB, Canada. [Zhao, Xin; Peterson, Eric D.; Xian, Ying; Olson, DaiWai M.] Duke Clin Rsch Inst, Durham, NC USA. [Hernandez, Adrian F.] Duke Clin Rsch Cntr, Durham, NC USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201496 ER PT J AU Giurgiutiu, DVV Yoo, AJ Fitzpatrick, K Chaudhry, Z Schwamm, LH Rost, NS AF Giurgiutiu, Dan-Victor V. Yoo, Albert J. Fitzpatrick, Kaitlin Chaudhry, Zeshan Schwamm, Lee H. Rost, Natalia S. TI Leukoaraiosis And Outcomes After Intra-arterial Therapy In Acute Ischemic Stroke SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Thrombolysis; Cerebrovascular disorders; Intervention; Aging C1 [Giurgiutiu, Dan-Victor V.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Yoo, Albert J.; Chaudhry, Zeshan] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Fitzpatrick, Kaitlin; Schwamm, Lee H.; Rost, Natalia S.] Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201241 ER PT J AU Haley, K van Etten, ES Auriel, E Ayres, A Vashkevich, A Reed, AK Dipucchio, ZY Schwab, KM Rosand, J Viswanathan, A Greenberg, SM Gurol, ME AF Haley, Kellen van Etten, Ellis S. Auriel, Eitan Ayres, Alison Vashkevich, Anastasia Reed, Anne K. Dipucchio, Zora Y. Schwab, Kristin M. Rosand, Jonathan Viswanathan, Anand Greenberg, Steven M. Gurol, Mahmut E. TI Different Patterns of Subcortical White Matter Disease in Patients with Cerebral Amyloid Angiopathy and Hypertensive Intracerebral Hemorrhage SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Cerebrovascular circulation; Magnetic resonance imaging; Stroke; Hypertension; Cerebrovascular disorders C1 [Haley, Kellen; van Etten, Ellis S.; Auriel, Eitan; Ayres, Alison; Vashkevich, Anastasia; Reed, Anne K.; Dipucchio, Zora Y.; Schwab, Kristin M.; Rosand, Jonathan; Viswanathan, Anand; Greenberg, Steven M.; Gurol, Mahmut E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200617 ER PT J AU Halm, E Nelson, C Tiro, J Sepucha, K Batchelor, K Xuan, L Fowler, J Stilwell, D Witteman, H Dickson, M Zikmund-Fisher, B AF Halm, Ethan Nelson, Colin Tiro, Jasmin Sepucha, Karen Batchelor, Kim Xuan, Lei Fowler, Jack Stilwell, Diana Witteman, Holly Dickson, Mark Zikmund-Fisher, Brian TI Development and Testing of a Web-Based Decision Aid to Improve Decision Making for Asymptomatic Carotid Disease SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Carotid arteries; Patient education/teaching psychosocial aspects; Disease management; Surgery C1 [Halm, Ethan; Tiro, Jasmin; Batchelor, Kim; Xuan, Lei] Univ TX Southwestern Med Ctr, Dallas, TX USA. [Nelson, Colin; Fowler, Jack; Stilwell, Diana] Informed Med Decis Fdn, Boston, MA USA. [Sepucha, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Witteman, Holly; Dickson, Mark; Zikmund-Fisher, Brian] Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201218 ER PT J AU Jung, JE van Leyen, K AF Jung, Joo Eun van Leyen, Klaus TI Stats Regulate Transcription Of 12/15-lox In Mouse Cortical Neurons Under Glutamate-induced Oxidative Stress SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Oxidative stress; Stroke C1 Massachusettes Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200440 ER PT J AU Katsnelson, MJ Rundek, T Sacco, R Worrall, BB Meschia, JF Ay, H Woo, D Brown, RD Rosand, J McArdle, P Wassertheil-Smoller, S Kaplan, R Arsava, EM Anderson, CD Helenius, J Biffi, A Kittner, S AF Katsnelson, Michael J. Rundek, Tatjana Sacco, Ralph Worrall, Bradford B. Meschia, James F. Ay, Hakan Woo, Daniel Brown, Robert D. Rosand, Jonathan McArdle, Patrick Wassertheil-Smoller, Sylvia Kaplan, Robert Arsava, Ethem M. Anderson, Christopher D. Helenius, Johanna Biffi, Alessandro Kittner, Steven CA NINDS Stroke Genetics Network SiGN TI Classification of Stroke Sub-types by Race-Ethnicities in the Stroke Genetics Network with Causative Classification System SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Genetics C1 [Katsnelson, Michael J.; Rundek, Tatjana; Sacco, Ralph] Univ Miami, Miami, FL USA. [Worrall, Bradford B.] Univ Virginia, Charlottesville, VA USA. [Meschia, James F.] Mayo Clin, Jacksonville, FL 32224 USA. [Ay, Hakan; Rosand, Jonathan; Arsava, Ethem M.; Anderson, Christopher D.; Helenius, Johanna; Biffi, Alessandro] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Woo, Daniel] Univ Cincinnati, Cincinnati, OH USA. [Brown, Robert D.] Mayo Clin, Rochester, MN USA. [McArdle, Patrick; Kittner, Steven] Univ Maryland, Baltimore, MD 21201 USA. [Wassertheil-Smoller, Sylvia; Kaplan, Robert] Einstein Coll Med, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200142 ER PT J AU Kemmling, A Kamalian, S Souza, L Lev, MH Fiehler, J Forkert, N AF Kemmling, Andre Kamalian, Shervin Souza, Leticia Lev, Michael H. Fiehler, Jens Forkert, Nils TI Improved Infarct Prediction After Acute Ischemic Stroke: A Priori Infarct Probability Defined By Site Of Vessel Occlusion Can Be Combined With Infarct Likelihood-ratios Based On Ct Perfusion Imaging SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Computed tomography; Perfusion imaging C1 [Kemmling, Andre; Fiehler, Jens; Forkert, Nils] Univ Med Cntr Hamburg Eppendorf, Hamburg, Germany. [Kamalian, Shervin; Souza, Leticia] Massachusetts Gen Hospita, Boston, MA USA. [Lev, Michael H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200375 ER PT J AU Kim, GM Noh, HJ Kim, SJ Lordelo, MD Oliveira, J Helenius, J Ay, H AF Kim, Gyeong-Moon Noh, Hyun Jin Kim, Suk Jae Lordelo, Morgana deJesus Oliveira Filho, Jamary Helenius, Johanna Ay, Hakan TI A Validation Study of Recurrence Risk Estimator Score in Acute Ischemic Stroke SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Prognosis; Magnetic resonance imaging; Risk factors C1 [Kim, Gyeong-Moon; Noh, Hyun Jin; Kim, Suk Jae] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. [Lordelo, Morgana deJesus; Oliveira Filho, Jamary] Univ Fed Bahia, Salvador, Brazil. [Helenius, Johanna] Univ Massachusetts, Sch Med, Worcester, MA USA. [Ay, Hakan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200276 ER PT J AU Kimberly, WT Wang, Y Pham, L Furie, KL Gerszten, RE AF Kimberly, W. Taylor Wang, Yu Ly Pham Furie, Karen L. Gerszten, Robert E. TI Metabolomics Identifies a Branched Chain Amino Acid Profile in Acute Ischemic Stroke SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Biomarkers; Stroke; Metabolism C1 [Kimberly, W. Taylor; Wang, Yu; Ly Pham; Furie, Karen L.; Gerszten, Robert E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200591 ER PT J AU Kleindorfer, D Smith, EE Fonarow, GC Grau-Sepulveda, MM Olson, DM Hernandez, AF Peterson, ED Schwamm, L AF Kleindorfer, Dawn Smith, Eric E. Fonarow, Gregg C. Grau-Sepulveda, Maria M. Olson, DaiWai M. Hernandez, Adrian F. Peterson, Eric D. Schwamm, Lee TI Are "Drip and Ship" Patients Different than Other rt-PA Treated Patients? Clinical Characteristics and Patient Outcomes. SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Thrombolysis; Stroke C1 [Kleindorfer, Dawn] Univ Cincinnati Hosp, Cincinnati, OH USA. [Smith, Eric E.] Univ Calgary, Calgary, AB, Canada. [Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA. [Grau-Sepulveda, Maria M.; Olson, DaiWai M.; Hernandez, Adrian F.; Peterson, Eric D.] Duke Univ, Raleigh, NC USA. [Schwamm, Lee] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201139 ER PT J AU Kursun, O Topcuoglu, MA Karatas, H Buonanno, FS Singhal, AB AF Kursun, Oguzhan Topcuoglu, Mehmet A. Karatas, Hulya Buonanno, Ferdinando S. Singhal, Aneesh B. TI Stroke in Infective Endocarditis: Impact of Management on Outcome Over 3 Decades SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Disease management; Heart valves C1 [Kursun, Oguzhan; Karatas, Hulya; Buonanno, Ferdinando S.; Singhal, Aneesh B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Topcuoglu, Mehmet A.] Hacettepe Univ, Ankara, Turkey. RI Karatas, Hulya/J-1459-2013 OI Karatas, Hulya/0000-0003-4838-6320 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200600 ER PT J AU Kursun, O Topcuoglu, MA Karatas, H Buonanno, FS Singhal, AB AF Kursun, Oguzhan Topcuoglu, Mehmet A. Karatas, Hulya Buonanno, Ferdinando S. Singhal, Aneesh B. TI Risk Factors for Stroke in Infective Endocarditis SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Valvular heart disease; Stroke; Transesophageal echocardiography C1 [Kursun, Oguzhan; Karatas, Hulya; Buonanno, Ferdinando S.; Singhal, Aneesh B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Karatas, Hulya/J-1459-2013 OI Karatas, Hulya/0000-0003-4838-6320 NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200548 ER PT J AU Lau, AY Wong, KSL Lev, M Furie, K Smith, W Kim, AS AF Lau, Alexander Y. Wong, K. S. Lawrence Lev, Michael Furie, Karen Smith, Wade Kim, Anthony S. TI Burden of Intracranial Steno-occlusive Lesions on Initial CT Angiography is Predictive of Poor Outcomes in Patients with Stroke And TIA SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Prognosis; Computed tomography C1 [Lau, Alexander Y.; Wong, K. S. Lawrence] Chinese Univ Hong Kong, Shatin, Hong Kong, Peoples R China. [Lev, Michael; Furie, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Smith, Wade; Kim, Anthony S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RI Lau, Alexander/N-2485-2015 OI Lau, Alexander/0000-0002-5933-9290 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201166 ER PT J AU Lorenzano, S Rost, NS Arai, K Thankachan, T Green, RE Dipietro, AJ Som, AT Pham, LDD Harris, GJ Blumberg, JB Feske, SK Lo, EH Furie, KL AF Lorenzano, Svetlana Rost, Natalia S. Arai, Ken Thankachan, Tijy Green, Rebecca E. Dipietro, Allison J. Som, Angel T. Pham, Loc-Duyen D. Harris, Gordon J. Blumberg, Jeffrey B. Feske, Steven K. Lo, Eng H. Furie, Karen L. TI Role of Plasma Biomarkers in Diagnosis of Ischemic Stroke Subtypes SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Biomarkers; Stroke C1 [Lorenzano, Svetlana; Rost, Natalia S.; Arai, Ken; Thankachan, Tijy; Green, Rebecca E.; Dipietro, Allison J.; Som, Angel T.; Pham, Loc-Duyen D.; Harris, Gordon J.; Lo, Eng H.; Furie, Karen L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Blumberg, Jeffrey B.] Tufts Univ, Boston, MA 02111 USA. [Feske, Steven K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Furie, Karen L.] Brown Univ, Rhode Isl Hosp, Alpert Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200547 ER PT J AU Lorenzano, S Rost, NS Green, RE Thankachan, T Dipietro, AJ Arai, K Som, AT Pham, LDD Harris, GJ Lo, EH Feske, SK Blumberg, JB Furie, KL AF Lorenzano, Svetlana Rost, Natalia S. Green, Rebecca E. Thankachan, Tijy Dipietro, Allison J. Arai, Ken Som, Angel T. Pham, Loc-Duyen D. Harris, Gordon J. Lo, Eng H. Feske, Steven K. Blumberg, Jeffrey B. Furie, Karen L. TI Hyperacute Plasma F2-Isoprostanes Predict Infarct Growth in Acute Ischemic Stroke SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Biomarkers; Stroke C1 [Lorenzano, Svetlana; Rost, Natalia S.; Green, Rebecca E.; Thankachan, Tijy; Dipietro, Allison J.; Arai, Ken; Som, Angel T.; Pham, Loc-Duyen D.; Harris, Gordon J.; Lo, Eng H.; Furie, Karen L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Feske, Steven K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Blumberg, Jeffrey B.] Tufts Univ, Boston, MA 02111 USA. [Furie, Karen L.] Brown Univ, Rhode Isl Hosp, Alpert Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200538 ER PT J AU Majersik, JJ Arsava, EM Brown, RD Grewal, R Jern, C Jimenez-Conde, J Jood, K Kittner, SJ Labovitz, DL Lindgren, A Meschia, JF Peddareddygari, LR Pera, J Rhodes, JD Rosand, J Rundek, T Slowik, A Southerland, AM Woo, D Worrall, BB Ay, H AF Majersik, Jennifer J. Arsava, Ethem M. Brown, Robert D. Grewal, Raji Jern, Christina Jimenez-Conde, Jordi Jood, Katarina Kittner, Steven J. Labovitz, Daniel L. Lindgren, Arne Meschia, James F. Peddareddygari, Leema R. Pera, Joanna Rhodes, J. D. Rosand, Jonathan Rundek, Tatjana Slowik, Agnieszka Southerland, Andrew M. Woo, Daniel Worrall, Bradford B. Ay, Hakan CA NINDS Stroke Genetics Network SIGN TI Yield of Diagnostic Evaluation in Major Stroke Phenoytypes SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Risk factors; Epidemiology; Cardiovascular imaging C1 [Majersik, Jennifer J.] Univ Utah, Salt Lake City, UT USA. [Arsava, Ethem M.] Hacettepe Univ, Ankara, Turkey. [Brown, Robert D.] Mayo Clin, Rochester, MN USA. [Grewal, Raji; Peddareddygari, Leema R.] St Francis Med Cntr, Trenton, NJ USA. [Jern, Christina] Gothenburg Univ, Sahlgrenska Acad, Gothenburg, Sweden. [Jimenez-Conde, Jordi] IMM Hosp del Mar, Barcelona, Spain. [Jood, Katarina] Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden. [Kittner, Steven J.] Univ Maryland, Baltimore, MD 21201 USA. [Labovitz, Daniel L.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Lindgren, Arne] Skane Univ Hosp, Lund, Sweden. [Meschia, James F.] Mayo Clin, Jacksonsville, FL USA. [Pera, Joanna; Slowik, Agnieszka] Jagiellonian Univ, Coll Med, Krakow, Poland. [Rhodes, J. D.] Univ Alabama Birmingham, Birmingham, AL USA. [Rosand, Jonathan; Ay, Hakan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rundek, Tatjana] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Southerland, Andrew M.; Worrall, Bradford B.] Univ Virginia, Charlottesville, VA USA. [Woo, Daniel] Univ Cincinnati, Coll Med, Cincinnati, OH USA. RI JIMENEZ-CONDE, JORDI/C-1941-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200274 ER PT J AU Martinez-Ramirez, S Pontes-Neto, O Dumas, AP Auriel, E Gurol, ME Greenberg, SM Viswanathan, A AF Martinez-Ramirez, Sergi Pontes-Neto, Octavio Dumas, Andrew P. Auriel, Eitan Gurol, Mahmut Edip Greenberg, Steven M. Viswanathan, Anand TI Topography of Dilated Perivascular Spaces in Patients with Markers of Cerebral Amyloid Angiopathy and Hypertensive Vasculopathy SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Hypertension; Magnetic resonance imaging C1 [Martinez-Ramirez, Sergi; Pontes-Neto, Octavio; Dumas, Andrew P.; Auriel, Eitan; Gurol, Mahmut Edip; Greenberg, Steven M.; Viswanathan, Anand] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Pontes-Neto, Octavio/G-4294-2012 OI Pontes-Neto, Octavio/0000-0003-0317-843X NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201448 ER PT J AU Miyamoto, N Hayakawa, K Pham, LDD Matsuzaki, T Seo, JH Kim, KW Magnain, C Boas, D Lo, EH Arai, K AF Miyamoto, Nobukazu Hayakawa, Kazuhide Pham, Loc-Duyen D. Matsuzaki, Toshinori Seo, Ji Hae Kim, Kyu-Won Magnain, Caroline Boas, David Lo, Eng H. Arai, Ken TI Age Related Decline Of Oligodendrogenesis After White Matter Injury SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Aging; Cerebrovascular disorders; Signal transduction; Antiplatelet drugs C1 [Miyamoto, Nobukazu; Hayakawa, Kazuhide; Pham, Loc-Duyen D.; Matsuzaki, Toshinori; Seo, Ji Hae; Lo, Eng H.; Arai, Ken] Massachusetts Gen Hosp, Neuroprotect Rsch Lab, Depts Radiol, Charlstown, MA USA. [Miyamoto, Nobukazu; Hayakawa, Kazuhide; Pham, Loc-Duyen D.; Matsuzaki, Toshinori; Seo, Ji Hae; Lo, Eng H.; Arai, Ken] Massachusetts Gen Hosp, Neuroprotect Rsch Lab, Depts Neurol, Charlstown, MA USA. [Miyamoto, Nobukazu; Hayakawa, Kazuhide; Pham, Loc-Duyen D.; Matsuzaki, Toshinori; Seo, Ji Hae; Lo, Eng H.; Arai, Ken] Harvard Univ, Sch Med, Charlstown, MA USA. [Kim, Kyu-Won] Seoul Natl Univ, NeuroVasc Coordinat Rsch Cntr, Coll Pharm, Seoul, South Korea. [Kim, Kyu-Won] Seoul Natl Univ, Rsch Inst Pharmaceut Sci, Seoul, South Korea. [Magnain, Caroline] Athinoula A Martinos Cntr Biomed Imaging, Dept Radiol, Charlstown, MA USA. [Boas, David] Massachusetts Gen Hosp, Athinoula A Martinos Cntr Biomed Imaging, Dept Radiol, Charlstown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201326 ER PT J AU Moore, WS Roubin, GS Rosenfield, K Altafullah, I Ansel, GM Voeks, JH Meschia, JF Lal, BK Howard, G Brott, TG AF Moore, Wesley S. Roubin, Gary S. Rosenfield, Kenneth Altafullah, Irfan Ansel, Gary M. Voeks, Jenifer H. Meschia, James F. Lal, Brajesh K. Howard, George Brott, Thomas G. TI Can Patient or Arterial Characteristics Guide the Choice between Carotid Angioplasty and Carotid Endarterectomy? The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Carotid arteries; Stroke; Prevention; Stent; Restenosis C1 [Moore, Wesley S.] Univ Calif Los Angeles, Med Cntr, Los Angeles, CA USA. [Roubin, Gary S.] Continuum Hlth Partners, New York, NY USA. [Rosenfield, Kenneth] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Altafullah, Irfan] North Mem Med Cntr, Robbinsdale, MN USA. [Ansel, Gary M.] Ohio Hlth Rsch Inst, Columbus, OH USA. [Voeks, Jenifer H.] Med Univ S Carolina, Charleston, SC 29425 USA. [Meschia, James F.; Brott, Thomas G.] Mayo Clin, Jacksonville, FL 32224 USA. [Lal, Brajesh K.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Howard, George] Univ Alabama Birmingham, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200070 ER PT J AU Ning, MM Cao, J Buonanno, FS Feeney, K Elia, MG McMullin, D Guo, SZ Arai, K Lo, EH AF Ning, MingMing Cao, Jing Buonanno, Ferdinando S. Feeney, Kathleen Elia, Mikaela G. McMullin, David Guo, Shu-Zhen Arai, Ken Lo, Eng H. TI Glyco-proteomic Study of Therapeutic Hypothermia in Global Ischemic Brain Injury Post Cardiac Arrest SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Cardiac arrest; Ischemia reperfusion C1 [Ning, MingMing; Cao, Jing; Buonanno, Ferdinando S.; Feeney, Kathleen; Elia, Mikaela G.; McMullin, David; Guo, Shu-Zhen; Arai, Ken; Lo, Eng H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201105 ER PT J AU Ning, MM Lopez, M Sarracino, DA Feeney, K Thayer, M Elia, M Koop, H McMullin, D Demirjian, Z Inglessis-Azuaje, I Silverman, S Dec, GW Palacios, I Lo, EH Buonanno, FS AF Ning, MingMing Lopez, Mary Sarracino, David A. Feeney, Kathleen Thayer, Molly Elia, Mikaela Koop, Hailey McMullin, David Demirjian, Zareh Inglessis-Azuaje, Ignacio Silverman, Scott Dec, G. W. Palacios, Igor Lo, Eng H. Buonanno, Ferdinando S. TI Plasma Proteomic Changes Persist in Long Term Follow-up of Patent Foramen Ovale Related Stroke Patients after PFO Closure SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Proteomics C1 [Ning, MingMing; Lopez, Mary; Sarracino, David A.; Feeney, Kathleen; Thayer, Molly; Elia, Mikaela; Koop, Hailey; McMullin, David; Demirjian, Zareh; Inglessis-Azuaje, Ignacio; Silverman, Scott; Dec, G. W.; Palacios, Igor; Lo, Eng H.; Buonanno, Ferdinando S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201103 ER PT J AU Ning, MM Cao, J Lopez, M Sarracino, DA McMullin, D Buonanno, FS Wang, XY Lo, EH AF Ning, MingMing Cao, Jing Lopez, Mary Sarracino, David A. McMullin, David Buonanno, Ferdinando S. Wang, Xiaoying Lo, Eng H. TI Quantitative Proteomic Profile of Tissue Plasminogen Activator (tPA) Responders SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Thrombolysis; Stroke C1 [Ning, MingMing; Cao, Jing; Lopez, Mary; Sarracino, David A.; McMullin, David; Buonanno, Ferdinando S.; Wang, Xiaoying; Lo, Eng H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200401 ER PT J AU Park, KY Helenius, J Avery, R Kim, GM Buonanno, FS Ay, H AF Park, Kwang-Yeol Helenius, Johanna Avery, Ross Kim, Gyeong-Moon Buonanno, Ferdinando S. Ay, Hakan TI The Effect of Hyperglycemia on Stroke Outcome Depends on Baseline Glycosylated Hemoglobin Levels SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Glucose; Infarct size; Stroke C1 [Park, Kwang-Yeol; Helenius, Johanna; Avery, Ross; Kim, Gyeong-Moon; Buonanno, Ferdinando S.; Ay, Hakan] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200083 ER PT J AU Pekcec, A Yigitkanli, K Jung, JE Karatas, H Lo, EH Van Leyen, K AF Pekcec, Anton Yigitkanli, Kazim Jung, Joo Eun Karatas, Hulya Lo, Eng H. Van Leyen, Klaus TI Remodeling After Stroke: The Recovering Brain Is Vulnerable To Lipoxygenase-dependent Semaphorin Signaling SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Remodeling; Oxidized lipids; Angiogenesis C1 [Pekcec, Anton; Yigitkanli, Kazim; Jung, Joo Eun; Karatas, Hulya; Lo, Eng H.; Van Leyen, Klaus] Massachusetts Gen Hosp, Charlestown, MA USA. RI Karatas, Hulya/J-1459-2013 OI Karatas, Hulya/0000-0003-4838-6320 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200090 ER PT J AU Pham, L O'Connor, S Yarbrough, K Jacobson, S Stern, BJ Sheth, KN Kimberly, WT AF Pham, Ly O'Connor, Sydney Yarbrough, Karen Jacobson, Sven Stern, Barney J. Sheth, Kevin N. Kimberly, W. Taylor TI Intravenous Glyburide Treatment is Associated with Reduced Matrix Metalloproteinase-9 in Human Acute Stroke SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Clinical trials; Biomarkers; Pharmacology C1 [Pham, Ly; O'Connor, Sydney; Kimberly, W. Taylor] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yarbrough, Karen; Stern, Barney J.; Sheth, Kevin N.] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. [Jacobson, Sven] Remedy Pharmaceut Inc, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200247 ER PT J AU Pontes-Neto, OM Martinez-Ramirez, S Viswanathan, A Auriel, E Schwab, KM Ayres, A Gurol, ME Rosand, J Greenberg, SM Goldstein, JN AF Pontes-Neto, Octavio M. Martinez-Ramirez, Sergi Viswanathan, Anand Auriel, Eitan Schwab, Kristen M. Ayres, Alison Gurol, M. Edip Rosand, Jonathan Greenberg, Steven M. Goldstein, Joshua N. TI Left Ventricle Hypertrophy is Common in Patients with Cerebral Amyloid Angiopathy-Related Intracerebral Hemorrhage and Is Independently Associated with Long-Term Mortality. SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Hypertension C1 [Pontes-Neto, Octavio M.; Martinez-Ramirez, Sergi; Viswanathan, Anand; Auriel, Eitan; Schwab, Kristen M.; Ayres, Alison; Gurol, M. Edip; Rosand, Jonathan; Greenberg, Steven M.; Goldstein, Joshua N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RI Pontes-Neto, Octavio/G-4294-2012; Goldstein, Joshua/H-8953-2016 OI Pontes-Neto, Octavio/0000-0003-0317-843X; NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201516 ER PT J AU Rosenthal, ES O'Connor, K Westover, MB AF Rosenthal, Eric S. O'Connor, Kathryn Westover, M. B. TI Effectiveness of EEG Ischemia Monitoring in Clinical Practice for the Detection of Delayed Cerebral Ischemia after Subarachnoid Hemorrhage SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Electrophysiology; Stroke; Aneurysms; Vasoconstriction; Disease management C1 [Rosenthal, Eric S.; O'Connor, Kathryn; Westover, M. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201226 ER PT J AU Ruff, IM Syed, A Rost, N Goldstein, J Lev, M Copen, W McIntyre, J Schwamm, L AF Ruff, Ilana M. Syed, Ali Rost, Natalia Goldstein, Joshua Lev, Michael Copen, William McIntyre, Joyce Schwamm, Lee TI Improving Door-to-Needle Times with Target Stroke SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Thrombolysis; Healthcare delivery systems C1 [Ruff, Ilana M.; Syed, Ali; Rost, Natalia; Goldstein, Joshua; Lev, Michael; Copen, William; McIntyre, Joyce; Schwamm, Lee] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200019 ER PT J AU Saver, JL Fonarow, GC Smith, EE Reeves, MJ Grau-Sepulveda, MV Pan, WQ Olson, D Hernandez, AF Peterson, ED Schwamm, LH AF Saver, Jeffrey L. Fonarow, Gregg C. Smith, Eric E. Reeves, Mathew J. Grau-Sepulveda, Maria V. Pan, Wenqin Olson, DaiWai Hernandez, Adrian F. Peterson, Eric D. Schwamm, Lee H. TI Time to Treatment with Intravenous Tissue Plasminogen Activator and Outcome from Acute Ischemic Stroke in the National US GWTG-Stroke Population SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Thrombolysis; Emergency care; Stroke; Fibrinolytic agents C1 [Saver, Jeffrey L.; Fonarow, Gregg C.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Smith, Eric E.] Univ Calgary, Calgary, AB, Canada. [Reeves, Mathew J.] Michigan State Univ, E Lansing, MI 48824 USA. [Grau-Sepulveda, Maria V.; Pan, Wenqin; Olson, DaiWai; Hernandez, Adrian F.; Peterson, Eric D.] Duke Clin Rsch Inst, Durham, NC USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200098 ER PT J AU Schwamm, LH Ali, SF Reeves, MJ Smith, EE Saver, JL Messe, S Bhatt, DL Grau-Sepulveda, MV Peterson, ED Fonarow, GC AF Schwamm, Lee H. Ali, Syed F. Reeves, Mathew J. Smith, Eric E. Saver, Jeffrey L. Messe, Steven Bhatt, Deepak L. Grau-Sepulveda, Maria V. Peterson, Eric D. Fonarow, Gregg C. TI Temporal Trends in Patient Characteristics and Use of IV tPA in Acute Ischemic Stroke Patients Treated at GWTG-Stroke Hospitals SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Thrombolysis; Healthcare delivery systems C1 [Schwamm, Lee H.; Ali, Syed F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Reeves, Mathew J.] Michigan State Univ, E Lansing, MI 48824 USA. [Smith, Eric E.] Univ Calgary, Calgary, AB, Canada. [Saver, Jeffrey L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Messe, Steven] Univ Penn, Philadelphia, PA 19104 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Grau-Sepulveda, Maria V.; Peterson, Eric D.] Duke Clin Rsch Cntr, Durham, NC USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200102 ER PT J AU Schwamm, LH Ali, SF Reeves, MJ Smith, EE Saver, JL Messe, S Bhatt, DL Grau-Sepulveda, MV Peterson, ED Fonarow, GC AF Schwamm, Lee H. Ali, Syed F. Reeves, Mathew J. Smith, Eric E. Saver, Jeffrey L. Messe, Steven Bhatt, Deepak L. Grau-Sepulveda, Maria V. Peterson, Eric D. Fonarow, Gregg C. TI Variation and Temporal Trends in the Characteristics of US Hospitals Treating Acute Ischemic Stroke Patients with IV-tPA: Findings from GWTG-Stroke SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Thrombolysis C1 [Schwamm, Lee H.; Ali, Syed F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Reeves, Mathew J.] Michigan State Univ, E Lansing, MI 48824 USA. [Smith, Eric E.] Univ Calgary, Calgary, AB, Canada. [Saver, Jeffrey L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Messe, Steven] Univ Penn, Philadelphia, PA 19104 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Grau-Sepulveda, Maria V.; Peterson, Eric D.] Duke Clin Rsch Cntr, Durham, NC USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200005 ER PT J AU Singhal, AB Kursun, O Topcuoglu, MA Fok, J Barton, B Muehlschlegel, S AF Singhal, Aneesh B. Kursun, Oguzhan Topcuoglu, Mehmet A. Fok, Joshua Barton, Bruce Muehlschlegel, Susanne TI Distinguishing RCVS-associated Subarachnoid Hemorrhage From Cryptogenic and Aneurysmal Subarachnoid Hemorrhage SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Aneurysms; Vasoconstriction; Cerebrovascular disorders C1 [Singhal, Aneesh B.; Kursun, Oguzhan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Topcuoglu, Mehmet A.] Hacettepe Univ, Ankara, Turkey. [Fok, Joshua] Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. [Barton, Bruce; Muehlschlegel, Susanne] Univ Massachusetts, Sch Med, Worcester, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201643 ER PT J AU Stein, J Bettger, JP Sicklick, A Hedeman, R Magdon-Ismail, Z Schwamm, LH AF Stein, Joel Bettger, Janet P. Sicklick, Alyse Hedeman, Robin Magdon-Ismail, Zainab Schwamm, Lee H. TI Patient-centered Predictors of Rehabilitation Care after Acute Stroke SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Rehabilitation C1 [Stein, Joel] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. [Bettger, Janet P.] Duke Univ, Durham, NC USA. [Sicklick, Alyse] Gaylord Hosp, Wallingford, CT USA. [Hedeman, Robin] Kessler Rehabil Hosp, W Orange, NJ USA. [Magdon-Ismail, Zainab] Amer Heart Assoc, Albany, NY USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201536 ER PT J AU Tirschwell, DL Chang, YC Ayres, AM Schwab, K Dipucchio, Z Vashkevich, A Viswanathan, A Greenberg, SM Goldstein, JN Rosand, J AF Tirschwell, David L. Chang, Yuchiao Ayres, Alison M. Schwab, Kristin Dipucchio, Zora Vashkevich, Anastasia Viswanathan, Anand Greenberg, Steven M. Goldstein, Joshua N. Rosand, Jonathan TI Estimating Supported Outcomes in Intracerebral Hemorrhage Patients with Withdrawal of Life Support through Propensity Score Matching SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Prognosis C1 [Tirschwell, David L.] Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. [Chang, Yuchiao] Mass Gen Hosp, Div Gen Med, Boston, MA USA. [Ayres, Alison M.; Schwab, Kristin; Dipucchio, Zora; Vashkevich, Anastasia; Viswanathan, Anand; Greenberg, Steven M.; Goldstein, Joshua N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rosand, Jonathan] Mass Gen Hosp, Dept Neurol, Boston, MA USA. RI Goldstein, Joshua/H-8953-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201527 ER PT J AU van Etten, ES Auriel, E Haley, KE McNamara, KA Ayres, AM Vashkevich, A Schwab, K Rosand, J Viswanathan, A Greenberg, SM Gurol, ME AF van Etten, Ellis S. Auriel, Eitan Haley, Kellen E. McNamara, Kristen A. Ayres, Alison M. Vashkevich, Anastasia Schwab, Kristin Rosand, Jonathan Viswanathan, Anand Greenberg, Steven M. Gurol, M. Edip TI Warfarin Increases Risk of Future Intracerebral Hemorrhage in Patients Presenting with Isolated Lobar Microbleeds on MRI SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Cerebrovascular disorders; Stroke; Magnetic resonance imaging; Risk factors; Anticoagulants C1 [van Etten, Ellis S.; Auriel, Eitan; Haley, Kellen E.; McNamara, Kristen A.; Ayres, Alison M.; Vashkevich, Anastasia; Schwab, Kristin; Rosand, Jonathan; Viswanathan, Anand; Greenberg, Steven M.; Gurol, M. Edip] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200622 ER PT J AU Walcott, BP Miller, JC Kwon, CS Sheth, SA Hiller, MR Cronin, CA Schwamm, LH Simard, JM Kimberly, WT Sheth, KN AF Walcott, Brian P. Miller, Jennifer C. Kwon, Churl S. Sheth, Sameer A. Hiller, Marc R. Cronin, Carolyn A. Schwamm, Lee H. Simard, J. Marc Kimberly, William T. Sheth, Kevin N. TI Concurrent Anterior Cerebral Artery Involvement Is Predictive of Mortality In Severe Middle Cerebral Artery Ischemic Stroke SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke volume; Stroke; Cerebrovascular circulation; Infarction; Prognosis C1 [Walcott, Brian P.; Kwon, Churl S.; Sheth, Sameer A.; Schwamm, Lee H.; Kimberly, William T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Miller, Jennifer C.; Hiller, Marc R.; Cronin, Carolyn A.; Simard, J. Marc; Sheth, Kevin N.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201369 ER PT J AU Wira, CR Magdon-Ismail, Z Melluzzo, S Day, D McCullough, LD Stein, J Schwamm, LH Gropen, T AF Wira, Charles R. Magdon-Ismail, Zainab Melluzzo, Shannon Day, David McCullough, Louise D. Stein, Joel Schwamm, Lee H. Gropen, Toby CA NorthEast Cerebrovasc Consortium TI Hospital Participation and Performance in Stroke Systems of Care: Results from The NorthEast Cerebrovascular Consortium (NECC) Region SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Healthcare delivery systems C1 [Wira, Charles R.] Yale Univ, Sch Med, New Haven, CT USA. [Magdon-Ismail, Zainab] Amer Stroke Assoc, Albany, NY USA. [Melluzzo, Shannon; Day, David] Amer Stroke Assoc, West Springfield, MA USA. [McCullough, Louise D.] Univ Connecticut, Ctr Hlth, Farmington, CT USA. [McCullough, Louise D.] Hartford Hosp, Stroke Cntr, Farmington, CT USA. [Stein, Joel] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Stein, Joel] Weill Cornell Med Coll, New York, NY USA. [Stein, Joel] NewYork Presbyterian Hosp, New York, NY USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schwamm, Lee H.] Harvard Univ, Sch Med, Boston, MA USA. [Gropen, Toby] Ochsner Med Cntr, New Orleans, LA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201594 ER PT J AU Wu, O Copen, WA Kwong, KK Kursun, O Mocking, S Benner, T Reese, TG Schaefer, PW Singhal, AB AF Wu, Ona Copen, William A. Kwong, Kenneth K. Kursun, Oguzhan Mocking, Steven Benner, Thomas Reese, Timothy G. Schaefer, Pamela W. Singhal, Aneesh B. TI Heterogeneity of Oxygen Extraction Fraction Weighted MRI in Acute Ischemic Stroke Patients SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Magnetic resonance imaging; Stroke; Brain; Cerebrovascular disorders; Vascular disease C1 [Wu, Ona; Copen, William A.; Kwong, Kenneth K.; Kursun, Oguzhan; Mocking, Steven; Benner, Thomas; Reese, Timothy G.; Schaefer, Pamela W.; Singhal, Aneesh B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201262 ER PT J AU Xian, Y Holloway, R Smith, E Schwamm, L Reeves, M Bhatt, D Cox, M Olson, D Hernandez, A Lytle, B Fonarow, G Peterson, E AF Xian, Ying Holloway, Robert Smith, Eric Schwamm, Lee Reeves, Mathew Bhatt, Deepak Cox, Margueritte Olson, DaiWai Hernandez, Adrian Lytle, Barbara Fonarow, Gregg Peterson, Eric TI Quality of Care and In-Hospital Outcomes by Race and Ethnicity among Patients Hospitalized with Intracerebral Hemorrhage: Findings from 123,623 Patients in the Get With The Guidelines-Stroke Program SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke C1 [Xian, Ying; Cox, Margueritte; Olson, DaiWai; Hernandez, Adrian; Lytle, Barbara; Peterson, Eric] Duke Clin Rsch Inst, Durham, NC USA. [Holloway, Robert] Univ Rochester, Rochester, NY USA. [Smith, Eric] Univ Calgary, Calgary, AB, Canada. [Schwamm, Lee] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Reeves, Mathew] Michigan State Univ, E Lansing, MI 48824 USA. [Bhatt, Deepak] Brigham & Womens Hosp, Boston, MA 02115 USA. [Fonarow, Gregg] Univ Calif Los Angeles, Los Angeles, CA USA. OI Smith, Eric/0000-0003-3956-1668 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201588 ER PT J AU Yoo, AJ Simonsen, CZ Prabhakaran, S Chaudhry, ZA Issa, M Fugate, JE Linfante, I Kallmes, DF Dabus, G Zaidat, OO AF Yoo, Albert J. Simonsen, Claus Z. Prabhakaran, Shyam Chaudhry, Zeshan A. Issa, Mohammad Fugate, Jennifer E. Linfante, Italo Kallmes, David F. Dabus, Guilherme Zaidat, Osama O. TI Refining Angiographic Biomarkers of Reperfusion: Modified TICI Is Superior to TIMI for Predicting Clinical Outcomes After Intra-arterial Therapy SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Intervention; Stroke; Reperfusion; Biomarkers C1 [Yoo, Albert J.; Chaudhry, Zeshan A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Simonsen, Claus Z.] Aarhus Med Cntr, Aarhus, Denmark. [Prabhakaran, Shyam] Northwestern Univ, Chicago, IL 60611 USA. [Issa, Mohammad; Zaidat, Osama O.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Fugate, Jennifer E.; Kallmes, David F.] Mayo Clin, Rochester, MN USA. [Linfante, Italo; Dabus, Guilherme] Baptist Cardiac & Vasc Inst, Miami, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540200063 ER PT J AU Yu, ZY Liu, N Li, YD Zhao, JH Lo, EH McCarthy, TJ Tedford, CE Wang, XY AF Yu, Zhanyang Liu, Ning Li, Yadan Zhao, Jianhua Lo, Eng H. McCarthy, Thomas J. Tedford, Clark E. Wang, Xiaoying TI Low Level Laser Therapy (LLLT) Protects Against Oxygen-Glucose Deprivation-Induced Neuron Death by Modulating Nitric Oxide and ROS Production In Vitro SO STROKE LA English DT Meeting Abstract CT American-Heart-Association/American-Stroke-Association International Stroke Conference / Nursing Symposium CY FEB 06-08, 2013 CL Honolulu, HI SP Amer Heart Assoc, Amer Stroke Assoc DE Stroke; Nitric oxide; Nitric oxide synthase; Reactive oxygen intermediates C1 [Yu, Zhanyang; Liu, Ning; Li, Yadan; Zhao, Jianhua; Lo, Eng H.; Wang, Xiaoying] Massachusetts Gen Hosp, Charlestown, MA USA. [McCarthy, Thomas J.; Tedford, Clark E.] PhotoThera, Carlsbad, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 EI 1524-4628 J9 STROKE JI Stroke PD FEB PY 2013 VL 44 IS 2 SU S PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 301NY UT WOS:000330540201154 ER PT J AU Goncalves, M Cook, B Mulvaney-Day, N Alegria, M Kinrys, G AF Goncalves, Marta Cook, Benjamin Mulvaney-Day, Norah Alegria, Margarita Kinrys, Gustavo TI Retention in mental health care of Portuguese-speaking patients SO TRANSCULTURAL PSYCHIATRY LA English DT Article DE adequate care; community mental health; mental health care; Portuguese-speaking patients; propensity scores; retention ID UNITED-STATES; PSYCHIATRIC-DISORDERS; ETHNIC-DIFFERENCES; NATIONAL SAMPLE; SERVICES; IMMIGRANTS; LANGUAGE; WHITES; DISPARITIES; MEDICATION AB We compared service outcomes of dedicated language and cultural competency services in adequacy of care, ER, and inpatient care among Portuguese-speaking patients in ethnic- and non-ethnic-specific behavioral health clinics. We assessed adequacy of mental health care, and use of inpatient emergency department among Portuguese-speaking patients, comparing individuals receiving care from a culturally and linguistically competent mental health care setting (the Portuguese Mental Health Program [PMHP]) with usual mental health care in a community health care system in the USA. Propensity score matching was used to balance patients in treatment and control groups on gender, marital status, age, diagnosis of mental disorder, and insurance status. We used de-identified, longitudinal, administrative data of 854 Portuguese-speaking patients receiving care from the PMHP and 541 Portuguese-speaking patients receiving usual care from 2005-2008. Adequate treatment was defined as receipt of at least eight outpatient psychotherapy visits, or at least four outpatient visits of which one was a psychopharmacological visit. PMHP patients were more likely to receive adequate care. No differences were found in rates of ER use or inpatient mental health care. The present study suggests increased quality of care for patients that have contact with a clinic that dedicates resources specifically to a minority/immigrant group. Advantages of this setting include greater linguistic and cultural concordance among providers and patients. Further research is warranted to better understand the mechanisms by which culturally appropriate mental health care settings benefit minority/immigrant patients. C1 [Goncalves, Marta] Inst Univ Lisboa ISCTE IUL, P-1649026 Lisbon, Portugal. [Goncalves, Marta] Harvard Univ, Sch Med, Ctr Multicultural Mental Hlth Res, Cambridge, MA 02138 USA. [Alegria, Margarita] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Kinrys, Gustavo] Harvard Univ, Sch Med, BCRP, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Goncalves, M (reprint author), Inst Univ Lisboa ISCTE IUL, Ctr Social Res & Intervent CIS, Av Forcas Armadas, P-1649026 Lisbon, Portugal. EM marta.goncalves@iscte.pt OI Goncalves, Marta/0000-0002-0232-2631 FU NIMH NIH HHS [R01 MH091042] NR 38 TC 0 Z9 0 U1 0 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1363-4615 EI 1461-7471 J9 TRANSCULT PSYCHIATRY JI Transcult. Psychiatry PD FEB PY 2013 VL 50 IS 1 BP 92 EP 107 DI 10.1177/1363461512474622 PG 16 WC Anthropology; Psychiatry SC Anthropology; Psychiatry GA AG8EW UT WOS:000335652600006 PM 23427258 ER PT J AU Carolan, PJ Melton, DA AF Carolan, Peter J. Melton, Douglas A. TI New findings in pancreatic and intestinal endocrine development to advance regenerative medicine SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Review DE embryonic stem cells; endocrine; epigenetics; intestine; mesenchyme; notch; pancreas ID INSULIN-PRODUCING CELLS; EMBRYONIC STEM-CELLS; PROGENITOR CELLS; TRANSCRIPTION FACTORS; BLOOD-VESSELS; IN-VITRO; DIFFERENTIATION; EXPRESSION; FATE; ARX AB Purpose of review We highlight some of the major recent advances that have been made towards understanding the mechanisms that control endocrine differentiation and cell identity in the pancreas and intestine. Recent findings Notch signaling plays a complex role in the fate choice between endocrine, duct, and acinar lineages in the developing pancreas. New approaches to dissecting the role of mesenchymal cells in the developing endocrine pancreas reveal inhibitory signals from the endothelium. Epigenetic mechanisms represent another layer of control over pancreatic development and beta cell identity. Further details on the transcriptional control of enteroendocrine cell development have emerged and revealed a surprising role for FoxO1 in restraining insulin expression in the gut. Incremental progress is being made in the field of directed differentiation of embryonic stem cells to pancreatic b cells and the first reported differentiation of human embryonic stem cells into intestinal organoids containing enteroendocrine cells represents a major breakthrough. Summary Greater knowledge of the fundamental processes controlling endocrine development in the pancreas and intestine has the potential to advance the field of regenerative medicine by providing a pathway to successfully create cell types of clinical interest. C1 [Carolan, Peter J.; Melton, Douglas A.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Carolan, Peter J.] Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Melton, DA (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Harvard Stem Cell Inst, 7 Divin Ave, Cambridge, MA 02138 USA. EM dmelton@harvard.edu NR 34 TC 5 Z9 5 U1 0 U2 26 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1752-296X J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD FEB PY 2013 VL 20 IS 1 BP 1 EP 7 DI 10.1097/MED.0b013e32835bc380 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 056ZC UT WOS:000312530200001 PM 23249759 ER PT J AU Levitsky, LL AF Levitsky, Lynne L. TI Pharmacologic and nutritional influences on growth SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Editorial Material ID FATTY-ACIDS; MEDICATION; CHILDREN; OMEGA-6 C1 Harvard Univ, Massachusetts Gen Hosp, Pediat Endocrine Unit, Sch Med, Boston, MA 02114 USA. RP Levitsky, LL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Pediat Endocrine Unit, Sch Med, 5th Floor Pediat,175 Cambridge St, Boston, MA 02114 USA. EM LLevitsky@partners.org NR 10 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1752-296X J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD FEB PY 2013 VL 20 IS 1 BP 37 EP 38 DI 10.1097/MED.0b013e32835c1ffd PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 056ZC UT WOS:000312530200007 PM 23247095 ER PT J AU Choi, JH Yoo, HW AF Choi, Jin-Ho Yoo, Han-Wook TI Control of puberty: genetics, endocrinology, and environment SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Review DE endocrine disrupting chemical; gonadotropin-releasing hormone; isolated gonadotropin-releasing hormone deficiency; precocious puberty ID IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; CENTRAL PRECOCIOUS PUBERTY; GENOME-WIDE ASSOCIATION; HORMONE SECRETION; SEXUAL PRECOCITY; FEMALE PUBERTY; MENARCHE; ONSET; AGE; MUTATIONS AB Purpose of review The aim of this review is to summarize recent advances regarding the genetic components of the complex and coordinated process of puberty, an update of the genes implicated in disorders of puberty, the endocrinologic changes of puberty, and influences of environment in the light of our current understanding of the mechanism of the onset of puberty. Recent findings The timing of puberty varies greatly in the general population among ethnic groups throughout the world, suggesting the genetic control of puberty. Several studies on the pathological conditions of pubertal onset provide unique information about the interactions of either the genetic susceptibility of or environmental influences on hypothalamic control of pubertal onset. However, these findings suggested that no isolated pathway or external factor is solely responsible for the neuroendocrine control of puberty. Summary Puberty is initiated by gonadotropin-releasing hormone from the hypothalamus followed by a complex sequence of endocrine changes and is regulated by both genetic and environmental factors. New attempts to use genetics and genomics might enhance our understanding of the spectrum of pubertal development. C1 [Choi, Jin-Ho; Yoo, Han-Wook] Univ Ulsan, Coll Med, Childrens Hosp, Dept Pediat,Asan Med Ctr, Seoul, South Korea. [Choi, Jin-Ho] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Harvard Reprod Endocrine Sci Ctr, Boston, MA 02114 USA. RP Choi, JH (reprint author), Univ Ulsan, Coll Med, Childrens Hosp, Dept Pediat,Asan Med Ctr, Seoul, South Korea. EM jhc@amc.seoul.kr NR 50 TC 15 Z9 17 U1 0 U2 62 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1752-296X J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD FEB PY 2013 VL 20 IS 1 BP 62 EP 68 DI 10.1097/MED.0b013e32835b7ec7 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 056ZC UT WOS:000312530200012 PM 23183357 ER PT J AU Choi, JH Lim, KH Park, E Kim, JY Choi, YK Baek, KH AF Choi, Jong-Ho Lim, Key-Hwan Park, Eunmi Kim, Ji-Young Choi, Young-Kil Baek, Kwang-Hyun TI Glutamate-ammonia ligase and reduction of G0 population in PANC-1 cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE GLUTAMATE-AMMONIA LIGASE (GLUL); GLUTAMINE; INS-1; PANC-1; PARTIAL PANCREATECTOMY (PPX); QUIESCENCE; REGENERATION ID INTESTINAL EPITHELIAL-CELLS; SYNTHETASE GENE-EXPRESSION; CRITICALLY-ILL PATIENTS; SKELETAL-MUSCLE; ENCHYTRAEUS-JAPONENSIS; PARTIAL-PANCREATECTOMY; PANCREAS REGENERATION; PROTEIN EXPRESSION; CYCLE PROGRESSION; MESSENGER-RNA AB In our previous study, we screened and isolated genes that were up-regulated after partial pancreatectomy using transcriptomic analysis and glutamate-ammonia ligase (GLUL) was selected for further study based on its effect on differentiation and proliferation. In the immunohistochemical analysis, GLUL was highly up-regulated in the acinar cells and the ductal cells in the pancreas damaged through partial pancreatectomy. Overexpression of GLUL enhanced the proliferation of PANC-1 cells and INS-1 cells. GLUL overexpression shifted the major population of PANC-1 cells from the G0/G1 phase to G2/M phase. In the double thymidine blocking analysis, similar cycle duration was observed between mock cells and GLUL-overexpressing cells while GLUL-overexpressing cells were partially resistant to thymidine blocking. In the FACS analysis of cells stained with Pyronin Y and Hoechst 33342, GLUL-overexpressing cells showed lower population of cells in the G0-quiescent phase than mock cells (512%). In addition, GLUL-overexpressing cells had high activation levels of AKT, ERK1/2, JNK, PCNA, c-FOS, and P70S6K in PANC-1 cells. Taken together, these results suggest that GLUL contributes to pancreatic regeneration. J. Cell. Biochem. 114: 303313, 2013. (c) 2012 Wiley Periodicals, Inc. C1 [Choi, Jong-Ho; Baek, Kwang-Hyun] CHA Univ, CHA Gen Hosp, Coll Med, Gyeonggi Do 463840, South Korea. [Lim, Key-Hwan; Baek, Kwang-Hyun] CHA Univ, CHA Gen Hosp, Dept Biomed Sci, Gyeonggi Do 463840, South Korea. [Park, Eunmi; Baek, Kwang-Hyun] Harvard Univ, Dana Farber Canc Inst, Div Radiat Oncol, Sch Med, Boston, MA 02115 USA. [Kim, Ji-Young] CHA Univ, CHA Gen Hosp, Dept Pathol, Seoul 135080, South Korea. [Choi, Young-Kil] CHA Univ, CHA Gen Hosp, Dept Internal Med, Seoul 135080, South Korea. RP Baek, KH (reprint author), CHA Univ, Dept Biomed Sci, 502 Yatap Dong, Songnam 463840, Gyeonggo Do, South Korea. EM baek@cha.ac.kr OI Baek, Kwang-Hyun/0000-0001-7662-7190 FU Korea Health 21 R&D Project, Ministry of Health, Welfare and Family Affaires, Republic of Korea [01-PJ10-PG6-01GN13-0002] FX Grant sponsor: Korea Health 21 R&D Project, Ministry of Health, Welfare and Family Affaires, Republic of Korea; Grant number: 01-PJ10-PG6-01GN13-0002. NR 56 TC 0 Z9 0 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD FEB PY 2013 VL 114 IS 2 BP 303 EP 313 DI 10.1002/jcb.24370 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 058RL UT WOS:000312651400008 PM 22930410 ER PT J AU Mantini, D Vanduffel, W AF Mantini, Dante Vanduffel, Wim TI Emerging Roles of the Brain's Default Network SO NEUROSCIENTIST LA English DT Review DE brain network; conscious experience; deactivation; spontaneous cognition; watchfulness ID INTRINSIC FUNCTIONAL ARCHITECTURE; STIMULUS-INDEPENDENT THOUGHT; POSTERIOR CINGULATE CORTEX; CONSCIOUS RESTING STATE; MODE NETWORK; CONNECTIVITY REFLECTS; SELF-CONSCIOUSNESS; PREFRONTAL CORTEX; WANDERING MINDS; WORKING-MEMORY AB During periods of inactivity, global metabolism does not decrease in the brain, and small but consistent increases in activity occur in a specific set of regions called the "default network". Although much is known about the topological and connectional properties of the default network, its functions remain a matter of debate. Functional neuroimaging and electrophysiological studies have suggested two apparently contrasting functions for this network: spontaneous cognition and monitoring the environment. Spontaneous cognition, however, is by default situated in a given external context, an external milieu to which we align ourselves and which must be monitored. This review integrates recent literature suggesting that the two proposed functions of the default network functions need not to be mutually exclusive, and that spontaneous cognition and monitoring of the environment represent complementary instances of conscious experiences occurring during idle moments of daily life. C1 [Vanduffel, Wim] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Mantini, Dante; Vanduffel, Wim] Katholieke Univ Leuven, Sch Med, Lab Neuro & Psychophysiol, Louvain, Belgium. [Vanduffel, Wim] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Vanduffel, W (reprint author), Athinoula A Martinos Ctr Biomed Imaging, 13th St,Bldg 149, Charlestown, MA 02129 USA. EM wim@nmr.mgh.harvard.edu RI Mantini, Dante/D-6989-2014 OI Mantini, Dante/0000-0001-6485-5559 FU European Union [FWP-200728]; Inter-University Attraction Pole [6/29]; Programme Financing [PFV/10/008]; Geconcerteerde Onderzoeks Actie [10/19]; Impulsfinanciering Zware Apparatuur and Hercules; Katholieke Universiteit Leuven, Fonds Wetenschappelijk Onderzoek-Vlaanderen [G062208N10, G083111N10, G043912N]; Fonds Wetenschappelijk Onderzoek-Vlaanderen; National Center for Research Resources [P41RR14075] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of t his article: The preparation of this manuscript received support from European Union Seventh Framework Programme FWP-200728, Inter-University Attraction Pole 6/29, Programme Financing PFV/10/008, Geconcerteerde Onderzoeks Actie 10/19, Impulsfinanciering Zware Apparatuur and Hercules funding of the Katholieke Universiteit Leuven, Fonds Wetenschappelijk Onderzoek-Vlaanderen G062208N10, G083111N10 and G043912N. D. M. is postdoctoral fellow of the Fonds Wetenschappelijk Onderzoek-Vlaanderen. The Martinos Center for Biomedical Imaging is supported by National Center for Research Resources grant P41RR14075. NR 66 TC 43 Z9 47 U1 5 U2 99 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD FEB PY 2013 VL 19 IS 1 BP 76 EP 87 DI 10.1177/1073858412446202 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 057FZ UT WOS:000312549600011 PM 22785104 ER PT J AU Haupt, R Minkov, M Astigarraga, I Schafer, E Nanduri, V Jubran, R Egeler, RM Janka, G Micic, D Rodriguez-Galindo, C Van Gool, S Visser, J Weitzman, S Donadieu, J AF Haupt, Riccardo Minkov, Milen Astigarraga, Itziar Schaefer, Eva Nanduri, Vasanta Jubran, Rima Egeler, R. Maarten Janka, Gritta Micic, Dragan Rodriguez-Galindo, Carlos Van Gool, Stefaan Visser, Johannes Weitzman, Sheila Donadieu, Jean CA Euro Histio Network TI Langerhans cell histiocytosis (LCH): Guidelines for diagnosis, clinical work-up, and treatment for patients till the age of 18 years SO PEDIATRIC BLOOD & CANCER LA English DT Article DE clinical work-up; diagnosis; follow-up; guidelines; Langerhans cell histiocytosis; therapy ID CENTRAL-NERVOUS-SYSTEM; ATAXIA RATING-SCALE; DIABETES-INSIPIDUS; RADIATION-THERAPY; FOLLOW-UP; FDG-PET; INVOLVEMENT; BONE; CHILDHOOD; DISEASE AB These guidelines for the management of patients up to 18 years with Langerhans cell histiocytosis (LCH) have been set up by a group of experts involved in the Euro Histio Net project who participated in national or international studies and in peer reviewed publications. Existing guidelines were reviewed and changed where new evidence was available in the literature up to 2012. Data and publications have been ranked according to evidence based medicine and when there was a lack of published data, consensus between experts was sought. Guidelines for diagnosis, initial clinical work-up, and treatment and long-term follow-up of LCH patients are presented. Pediatr Blood Cancer 2013;60:175184. (c) 2012 Wiley Periodicals, Inc. C1 [Donadieu, Jean] Hop Trousseau, Assistance Publ Hop Paris, Serv Hemato Oncol Pediat, Reference Ctr Histiocytosis, F-75012 Paris, France. [Haupt, Riccardo] Ist Giannina Gaslini, Dept Hematol & Oncol, Epidemiol & Biostat Sect, I-16148 Genoa, Italy. [Minkov, Milen] St Anna Childrens Hosp, Childrens Canc Res Inst, A-1090 Vienna, Austria. [Astigarraga, Itziar] Hosp Univ Cruces Barakaldo, Baracaldo, Spain. [Nanduri, Vasanta] Watford Dist Gen Hosp, Watford, England. [Jubran, Rima] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Egeler, R. Maarten; Weitzman, Sheila] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Janka, Gritta] Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany. [Micic, Dragan] Mother & Child Hlth Inst Serbia Dr Vukan Cupic, Belgrade, Serbia. [Rodriguez-Galindo, Carlos] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Van Gool, Stefaan] Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. [Visser, Johannes] Leicester Childrens Hosp, Univ Hosp Leicester, Leicester, Leics, England. RP Donadieu, J (reprint author), Hop Trousseau, Assistance Publ Hop Paris, Serv Hemato Oncol Pediat, Reference Ctr Histiocytosis, 26 Ave Dr Netter, F-75012 Paris, France. EM jean.donadieu@trs.aphp.fr RI Astigarraga, I/I-1215-2014; OI Astigarraga, I/0000-0002-5012-0137; Haupt, Riccardo/0000-0003-0571-8460 NR 60 TC 62 Z9 77 U1 4 U2 20 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD FEB PY 2013 VL 60 IS 2 BP 175 EP 184 DI 10.1002/pbc.24367 PG 10 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 057IW UT WOS:000312557600003 PM 23109216 ER PT J AU Perez-Cuevas, R Doubova, SV Zapata-Tarres, M Flores-Hernandez, S Frazier, L Rodriguez-Galindo, C Cortes-Gallo, G Chertorivski-Woldenberg, S Munoz-Hernandez, O AF Perez-Cuevas, Ricardo Doubova, Svetlana V. Zapata-Tarres, Marta Flores-Hernandez, Sergio Frazier, Lindsay Rodriguez-Galindo, Carlos Cortes-Gallo, Gabriel Chertorivski-Woldenberg, Salomon Munoz-Hernandez, Onofre TI Scaling up cancer care for children without medical insurance in developing countries: The case of Mexico SO PEDIATRIC BLOOD & CANCER LA English DT Article DE childhood cancer; developing countries; survival experience ID ACUTE LYMPHOBLASTIC-LEUKEMIA; LOW-INCOME COUNTRIES; CHILDHOOD-CANCER; HODGKIN LYMPHOMA; UNITED-STATES; SURVIVAL; EPIDEMIOLOGY; EUROPE; TRENDS; CLASSIFICATION AB Background In 2006, the Mexican government launched the Fund for Protection Against Catastrophic Expenditures (FPGC) to support financially healthcare of high cost illnesses. This study aimed at answering the question whether FPGC improved coverage for cancer care and to measure survival of FPGC affiliated children with cancer. Procedure A retrospective cohort study (20062009) was conducted in 47 public hospitals. Information of children and adolescents with cancer was analyzed. The coverage was estimated in accordance with expected number of incident cases and those registered at FPGC. The survival was analyzed by using KaplanMeier survival curves and Cox proportional hazards regression modeling. Results The study included 3,821 patients. From 2006 to 2009, coverage of new cancer cases increased from 3.3% to 55.3%. Principal diagnoses were acute lymphoblastic leukemia (ALL, 46.4%), central nervous system (CNS) tumors (8.2%), and acute myeloid leukemia (AML, 7.4%). The survival rates at 36 months were ALL (50%), AML (30.5%), Hodgkin lymphoma (74.5%), Non-Hodgkin lymphoma (40.1%), CNS tumors (32.8%), renal tumors (58.4%), bone tumors (33.4%), retinoblastoma (59.2%), and other solid tumors (52.6%). The 3-year overall survival rates varied among the regions; children between the east and south-southeast had the higher risks (hazard ratio 3.0; 95% CI: 2.33.9) and 2.4; 95% CI: 2.02.8) of death from disease when compared with those from the central region. Conclusion FPGC has increased coverage of cancer cases. Survival rates were different throughout the country. It is necessary to evaluate the effectiveness of this policy to increase access and identify opportunities to reduce the differences in survival. Pediatr Blood Cancer 2013;60:196203. (c) 2012 Wiley Periodicals, Inc. C1 [Perez-Cuevas, Ricardo] Inter Amer Dev Bank, Div Social Protect & Hlth, Mexico City 06600, DF, Mexico. [Doubova, Svetlana V.] Mexican Inst Social Secur, Epidemiol & Hlth Serv Res Unit CMN Siglo 21, Mexico City, DF, Mexico. [Zapata-Tarres, Marta] Hosp Infantil Mexico Dr Federico Gomez, Dept Oncol, Mexico City, DF, Mexico. [Flores-Hernandez, Sergio] Natl Inst Publ Hlth, Ctr Res Populat Hlth, Cuernavaca, Morelos, Mexico. [Frazier, Lindsay; Rodriguez-Galindo, Carlos] Harvard Univ, Sch Med, Boston, MA USA. [Frazier, Lindsay; Rodriguez-Galindo, Carlos] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cortes-Gallo, Gabriel] Med Insurance New Generat Program, Mexico City, DF, Mexico. [Chertorivski-Woldenberg, Salomon] Minist Hlth, Mexico City, DF, Mexico. [Munoz-Hernandez, Onofre] Hosp Infantil Mexico Dr Federico Gomez, Div Res, Mexico City, DF, Mexico. RP Perez-Cuevas, R (reprint author), Inter Amer Dev Bank, Div Social Protect & Hlth, Paseo Reforma 222, Mexico City 06600, DF, Mexico. EM rperez@iadb.org FU System for Social Protection for Health FX This study was funded by the System for Social Protection for Health funded this study. We thank Magdalena Suarez for her technical assistance in managing the database. NR 45 TC 13 Z9 13 U1 0 U2 19 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD FEB PY 2013 VL 60 IS 2 BP 196 EP 203 DI 10.1002/pbc.24265 PG 8 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 057IW UT WOS:000312557600005 PM 22887842 ER PT J AU Monje, M Thomason, ME Rigolo, L Wang, YL Waber, DP Sallan, SE Golby, AJ AF Monje, Michelle Thomason, Moriah E. Rigolo, Laura Wang, Yalin Waber, Deborah P. Sallan, Stephen E. Golby, Alexandra J. TI Functional and structural differences in the hippocampus associated with memory deficits in adult survivors of acute lymphoblastic leukemia SO PEDIATRIC BLOOD & CANCER LA English DT Article DE ALL; fMRI; hippocampus; late effects of cancer therapy; memory ID CENTRAL-NERVOUS-SYSTEM; ACUTE LYMPHOCYTIC-LEUKEMIA; MILD COGNITIVE IMPAIRMENT; LONG-TERM SURVIVORS; CRANIAL IRRADIATION; NEUROCOGNITIVE SEQUELAE; BRAIN RADIOTHERAPY; RADIATION-THERAPY; CHILDREN; CHILDHOOD AB Background Radiation and chemotherapy targeted to the central nervous system (CNS) can cause cognitive impairment, including impaired memory. These memory impairments may be referable to damage to hippocampal structures resulting from CNS treatment. Procedure In the present study, we explored episodic memory and its neuroimaging correlates in 10 adult survivors of childhood acute lymphoblastic leukemia (ALL) treated with cranial radiation therapy and both systemic and intrathecal chemotherapy and 10 controls matched for age and sex, using a subsequent memory paradigm after episodic encoding of visual scenes. Results We report behavioral, structural, and functional changes in the brains of the adult survivors. They demonstrated poorer recognition memory, hippocampal atrophy, and altered blood oxygenation level-dependent (BOLD) signal in the hippocampus. Whole brain statistical map analysis revealed increased BOLD signal/activation in several brain regions during unsuccessful encoding in ALL survivors, potentially reflecting ineffective neural recruitment. Individual differences in memory performance in ALL participants were related to magnitude of BOLD response in regions associated with successful encoding. Conclusions Taken together, these findings describe long term neuroimaging correlates of cognitive dysfunction after childhood exposure to CNS-targeted cancer therapies, suggesting enduring damage to episodic memory systems. Pediatr Blood Cancer 2013;60:293300. (c) 2012 Wiley Periodicals, Inc. C1 [Monje, Michelle] Stanford Univ, Dept Neurol, Stanford, CA 94305 USA. [Thomason, Moriah E.] Wayne State Univ, Merrill Palmer Skillman Inst Child & Family Dev, Detroit, MI USA. [Thomason, Moriah E.] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA. [Rigolo, Laura; Golby, Alexandra J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. [Rigolo, Laura; Golby, Alexandra J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Wang, Yalin] Arizona State Univ, Sch Comp Informat & Decis Syst Engn, Tempe, AZ 85287 USA. [Waber, Deborah P.] Childrens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Sallan, Stephen E.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Monje, M (reprint author), Lorry I Lokey Stem Cell Bldg,265 Campus Dr,G3077, Stanford, CA 94305 USA. EM mmonje@stanford.edu FU Hagerty Foundation; The National Institute of Mental Health [MH081583]; NARSAD Young Investigator Award; National Institutes of Health [P41EB015898, P41RR019703]; Brain Science Foundation; Klarman Family Foundation; National Institute of Mental Health [MH081583] FX Grant sponsor: Hagerty Foundation; Grant sponsor: The National Institute of Mental Health; Grant number: MH081583; Grant sponsor: NARSAD Young Investigator Award; Grant sponsor: The National Institutes of Health; Grant numbers: P41EB015898, P41RR019703; Grant sponsor: Brain Science Foundation; Grant sponsor: Klarman Family Foundation.; The authors gratefully acknowledge the support of the Hagerty Foundation (M. M.), the National Institute of Mental Health (MH081583, M. E. T., National Institutes of Health (P41EB015898 and P41RR019703 A.J.G.), the Brain Science Foundation (A.J.G.), the Klarman Family Foundation (A.J.G.)) and a NARSAD Young Investigator Award (M. E. T.) The authors thank Rebecca F. Johnson for her assistance with hippocampal volume tracing. NR 50 TC 16 Z9 16 U1 3 U2 20 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD FEB PY 2013 VL 60 IS 2 BP 293 EP 300 DI 10.1002/pbc.24263 PG 8 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 057IW UT WOS:000312557600021 PM 22887801 ER PT J AU La Madrid, AM Nall, MB Ouyang, K Minor, A Raca, G Kent, P Miller, I Schleiermacher, G Janoueix-Lerosey, I Cohn, SL AF La Madrid, Andres Morales Nall, Melanie Beglin Ouyang, Karen Minor, Agata Raca, Gordana Kent, Paul Miller, Ira Schleiermacher, Gudrun Janoueix-Lerosey, Isabelle Cohn, Susan L. TI Two cases of localized neuroblastoma with multiple segmental chromosomal alterations and metastatic progression SO PEDIATRIC BLOOD & CANCER LA English DT Article DE localized neuroblastoma; metastatic relapse; segmental chromosomal alterations ID RISK NEUROBLASTOMA; CHEMOTHERAPY AB Surgery alone is curative for most children with localized MYCN-non-amplified neuroblastoma. However, 1015% will develop recurrent loco-regional disease, and very rarely, patients will relapse metastatically. Currently, it is not possible to predict which child with localized, MYCN-non-amplified neuroblastoma will develop disseminated disease. We report two children who presented with favorable biology, localized neuroblastoma and subsequently relapsed with metastatic disease after treatment with surgery. Whole-genome DNA copy number analyses performed on the diagnostic tumors identified 15 (case 1) and 8 (case 2) segmental chromosomal alterations. Further analysis of the prognostic value of whole-genome analysis in children with localized neuroblastoma is warranted. Pediatr Blood Cancer 2013;60:332335. (c) 2012 Wiley Periodicals, Inc. C1 [Nall, Melanie Beglin; Cohn, Susan L.] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. [La Madrid, Andres Morales; Cohn, Susan L.] Boston Childrens Hosp, Dana Farber Canc Inst, Dept Neurooncol, Boston, MA USA. [Ouyang, Karen; Minor, Agata; Raca, Gordana] Univ Chicago, Canc Cytogenet Lab, Dept Med, Chicago, IL 60637 USA. [Kent, Paul] Rush Univ, Dept Pediat, Chicago, IL 60612 USA. [Miller, Ira] Rush Univ, Dept Pathol, Chicago, IL 60612 USA. [Schleiermacher, Gudrun; Janoueix-Lerosey, Isabelle] Inst Curie, Paris, France. RP Cohn, SL (reprint author), Univ Chicago, Dept Pediat, KCBD 5th Floor,Rm5100,900 E 57th St, Chicago, IL 60637 USA. EM scohn@peds.bsd.uchicago.edu OI Cohn, Susan/0000-0001-5749-7650 FU Little Heroes Cancer Research Foundation; Neuroblastoma Children's Cancer Society; Super Jake Foundation; Elise Anderson Neuroblastoma Research Fund; Conquer Cancer Foundation; St. Baldrick's Foundation FX Grant sponsor: Little Heroes Cancer Research Foundation; Grant sponsor: Neuroblastoma Children's Cancer Society; Grant sponsor: Super Jake Foundation; Grant sponsor: Elise Anderson Neuroblastoma Research Fund; Grant sponsor: Conquer Cancer Foundation; Grant sponsor: St. Baldrick's Foundation. NR 12 TC 2 Z9 2 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD FEB PY 2013 VL 60 IS 2 BP 332 EP 335 DI 10.1002/pbc.24311 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 057IW UT WOS:000312557600028 ER PT J AU Hunger, SP Baruchel, A Biondi, A Evans, WE Jeha, S Loh, M Moericke, A Pieters, R Relling, MV Schmiegelow, K Schrappe, M Silverman, LB Stanulla, M Valsecchi, MG Vora, A Pui, CH AF Hunger, Stephen P. Baruchel, Andre Biondi, Andrea Evans, William E. Jeha, Sima Loh, Mignon Moericke, Anja Pieters, Rob Relling, Mary V. Schmiegelow, Kjeld Schrappe, Martin Silverman, Lewis B. Stanulla, Martin Valsecchi, Maria Grazia Vora, Ajay Pui, Ching-Hon TI The thirteenth international childhood acute lymphoblastic leukemia workshop report: La Jolla, CA, USA, December 7-9, 2011 SO PEDIATRIC BLOOD & CANCER LA English DT Article ID CHILDRENS ONCOLOGY GROUP; MINIMAL RESIDUAL DISEASE; BFM STUDY-GROUP; CRANIAL IRRADIATION; L-ASPARAGINASE; B-PROGENITOR; CRLF2; RISK; REARRANGEMENT; INDUCTION C1 [Hunger, Stephen P.] Childrens Hosp Colorado, Ctr Canc & Blood Disorders, Aurora, CO 80045 USA. [Hunger, Stephen P.] Univ Colorado, Dept Pediat, Sch Med, Aurora, CO USA. [Hunger, Stephen P.; Loh, Mignon] Childrens Oncol Grp, Philadelphia, PA USA. [Baruchel, Andre] Univ Paris Diderot, Paris, France. [Baruchel, Andre] French Acute Lymphoblast Leukemia Study Grp, Paris, France. [Biondi, Andrea] Univ Milano Bicocca, Dept Pediat, M Tettamanti Res Ctr, Monza, MI, Italy. [Evans, William E.; Relling, Mary V.] Assoc Italiana Ematol & Oncol Pediat, Monza, MI, Italy. [Evans, William E.; Jeha, Sima; Relling, Mary V.; Pui, Ching-Hon] Univ Tennessee, Ctr Hlth Sci, Dept Pharmaceut Sci, St Jude Childrens Res Hosp, Memphis, TN 38163 USA. [Loh, Mignon] Univ Tennessee, Ctr Hlth Sci, Dept Oncol, St Jude Childrens Res Hosp, Memphis, TN 38163 USA. [Loh, Mignon] Univ Tennessee, Ctr Hlth Sci, Dept Pathol, St Jude Childrens Res Hosp, Memphis, TN 38163 USA. [Moericke, Anja; Schrappe, Martin] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. [Moericke, Anja; Schrappe, Martin; Stanulla, Martin] Berlin Frankfurt Munster Grp, Kiel, Germany. [Pieters, Rob] Erasmus MC Sophia Childrens Hosp, Rotterdam, Netherlands. [Pieters, Rob] Dutch Childhood Oncol Grp, The Hague, Netherlands. [Schmiegelow, Kjeld] Natl Univ Hosp, Pediat Clin, Copenhagen, Denmark. [Schmiegelow, Kjeld] Nord Soc Pediat Hematol & Oncol, Copenhagen, Denmark. [Silverman, Lewis B.] Childrens Hosp, Dana Farber Canc Inst, Div Hematol Oncol, Dept Pediat Oncol, Boston, MA 02115 USA. [Stanulla, Martin] Hannover Med Sch, Dept Mol Hematopoiesis, D-3000 Hannover, Germany. [Valsecchi, Maria Grazia] Univ Milano Bicocca, Dept Clin Med & Prevent, Ctr Biostat Clin Epidemiol, Monza, Italy. [Vora, Ajay] Sheffield Childrens Hosp, Dept Paediat Haematol, Sheffield, S Yorkshire, England. [Vora, Ajay] Univ Birmingham, United Kingdom Med Res Council Acute Lymphoblast, Birmingham, W Midlands, England. RP Hunger, SP (reprint author), Childrens Hosp Colorado, Ctr Canc & Blood Disorders, 13123 E 16th Ave,Box B115, Aurora, CO 80045 USA. EM stephen.hunger@childrenscolorado.org FU Sigma Tau Pharmaceuticals; CureSearch FX Grant sponsor: Sigma Tau Pharmaceuticals; Grant sponsor: CureSearch. NR 64 TC 6 Z9 7 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 EI 1545-5017 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD FEB PY 2013 VL 60 IS 2 BP 344 EP 348 DI 10.1002/pbc.24354 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 057IW UT WOS:000312557600033 PM 23024117 ER PT J AU Katz, IT Ybarra, ML Wyatt, MA Kiwanuka, JP Bangsberg, DR Ware, NC AF Katz, Ingrid T. Ybarra, Michele L. Wyatt, Monique A. Kiwanuka, Julius P. Bangsberg, David R. Ware, Norma C. TI Socio-cultural and economic antecedents of adolescent sexual decision-making and HIV-risk in rural Uganda SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE HIV prevention; adolescents; Uganda; sexual risk-taking ID SCHOOL ADOLESCENTS; PERCEPTIONS; KNOWLEDGE; EDUCATION; STUDENTS; BEHAVIOR; WOMEN AB With more than half of new infections occurring among youth, HIV/AIDS remains a major contributor to morbidity and mortality in Uganda. Semi-structured interviews were performed with 48 adolescents and 15 adult key informants in a rural Ugandan community to identify influences on adolescent sexual decision-making. Inductive data analytic methods revealed five thematic influences: (1) social pressure, (2) decline of the Senga (a familial figure who traditionally taught female adolescents about how to run a household), (3) cultural barriers to condom use, (4) knowledge of HIV transmission and modes of prevention, and (5) a moral injunction against sex before marriage. Influences were classified as HIV/AIDS risk and protective factors and organized to form an explanatory framework of adolescent sexual risk-taking. Risk factors pull youth toward risky behavior, while protective factors push them away. Predominance of risk over protective influences explains persistent sexual risk-taking by Ugandan youth. HIV prevention programs designed for Ugandan adolescents should take competing factors and sociocultural and economic influences into account. C1 [Katz, Ingrid T.] Brigham & Womens Hosp, Div Womens Hlth, Boston, MA 02115 USA. [Katz, Ingrid T.; Wyatt, Monique A.; Bangsberg, David R.; Ware, Norma C.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA USA. [Ybarra, Michele L.] Ctr Innovat Publ Hlth Res Inc, San Clemente, CA USA. [Kiwanuka, Julius P.; Bangsberg, David R.] Mbarara Univ Sci & Technol, Dept Paediat, Mbarara, Uganda. [Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Bangsberg, David R.] Ragon Inst MGH MIT & Harvard, Boston, MA USA. RP Katz, IT (reprint author), Brigham & Womens Hosp, Div Womens Hlth, 75 Francis St, Boston, MA 02115 USA. EM ikatz2@partners.org FU NCRR NIH HHS [UL1 RR025758]; NIAAA NIH HHS [K24 AA015287]; NIAID NIH HHS [P30 AI060354]; NIMH NIH HHS [5R01MH080662-02, K23 MH097667, K24 MH087227, K24 MH090894, R01 MH080662, R01 MH054907] NR 43 TC 6 Z9 6 U1 1 U2 12 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PD FEB 1 PY 2013 VL 25 IS 2 BP 258 EP 264 DI 10.1080/09540121.2012.701718 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 055VG UT WOS:000312445300016 PM 22835224 ER PT J AU Koyama, A Stone, K Yaffe, K AF Koyama, Alain Stone, Katie Yaffe, Kristine TI Serum oxidized low-density lipoprotein level and risk of cognitive impairment in older women SO NEUROBIOLOGY OF AGING LA English DT Article DE Dementia; Alzheimer's disease; Oxidized LDL; Inflammation; Oxidative stress ID ALZHEIMERS-DISEASE; DEMENTIA; LDL; INFLAMMATION AB We investigated the association between serum level of oxidized low-density lipoprotein (oxLDL) and risk of cognitive impairment (dementia or mild cognitive impairment) among 572 nondemented community-dwelling women from a prospective cohort study of aging. After 5 years of follow-up, 228 (39.9%) developed cognitive impairment; and this did not differ by tertile of baseline oxLDL level (highest compared with lowest tertile 38.2% vs. 39.5%; odds ratio, 0.90; 95% confidence interval, 0.63-1.43). Multivariate adjustment produced similar results (odds ratio, 0.91; 95% confidence interval, 0.60-1.39). These findings suggest that increased levels of serum oxLDL are not associated with a greater risk of incident cognitive impairment in older women. (C) 2013 Elsevier Inc. All rights reserved. C1 [Koyama, Alain] No Calif Inst Res & Educ, San Francisco, CA USA. [Koyama, Alain; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Stone, Katie] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Koyama, A (reprint author), 4150 Clement St,VAMC 116H, San Francisco, CA 94121 USA. EM alain.koyama@va.gov FU National Institute of Aging [K24 AG 031155, R01 AG 026720]; Alzheimer's Association [IIRG-08-88872]; National Institutes of Health; National Institute on Aging (NIA) [R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, R01 AG027576] FX This study was supported in part by grants K24 AG 031155 and R01 AG 026720 from the National Institute of Aging and grant IIRG-08-88872 from the Alzheimer's Association. The Study of Osteoporotic Fractures (SOF) is supported by the National Institutes of Health. The National Institute on Aging (NIA) provides support under the following grant numbers: R01 AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01 AG027574, and R01 AG027576. NR 15 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD FEB PY 2013 VL 34 IS 2 BP 634 EP U293 DI 10.1016/j.neurobiolaging.2012.02.030 PG 4 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 053HX UT WOS:000312263200025 PM 22483339 ER PT J AU Cassioli, A Chiavaioli, A Manes, C Sciandrone, M AF Cassioli, A. Chiavaioli, A. Manes, C. Sciandrone, M. TI An incremental least squares algorithm for large scale linear classification SO EUROPEAN JOURNAL OF OPERATIONAL RESEARCH LA English DT Article DE Large scale optimization; Machine learning; Linear classification; Incremental algorithms ID SUPPORT VECTOR MACHINES; OPTIMIZATION AB In this work we consider the problem of training a linear classifier by assuming that the number of data is huge (in particular, data may be larger than the memory capacity). We propose to adopt a linear least-squares formulation of the problem and an incremental recursive algorithm which requires to store a square matrix (whose dimension is equal to the number of features of the data). The algorithm (very simple to implement) converges to the solution using each training data once, so that it effectively handles possible memory issues and is a viable method for linear large scale classification and for real time applications, provided that the number of features of the data is not too large (say of the order of thousands). The extensive computational experiments show that the proposed algorithm is at least competitive with the state-of-the-art algorithms for large scale linear classification. (c) 2012 Elsevier B.V. All rights reserved. C1 [Cassioli, A.; Chiavaioli, A.; Sciandrone, M.] Univ Florence, Dipartimento Sistemi & Informat, I-50139 Florence, Italy. [Manes, C.] Univ Aquila, Dip Ingn & Sci Informaz & Matemat, I-67100 Coppito, AQ, Italy. [Cassioli, A.] Radiat Oncol Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cassioli, A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Cassioli, A (reprint author), Univ Florence, Dipartimento Sistemi & Informat, Via S Marta 3, I-50139 Florence, Italy. EM cassioli@dsi.unifi.it; alessandrochiavaioli@gmail.com; costanzo.manes@univaq.it; sciandro@dsi.unifi.it RI Manes, Costanzo/E-2790-2015 OI Manes, Costanzo/0000-0002-0771-7413 NR 24 TC 2 Z9 2 U1 0 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0377-2217 EI 1872-6860 J9 EUR J OPER RES JI Eur. J. Oper. Res. PD FEB 1 PY 2013 VL 224 IS 3 BP 560 EP 565 DI 10.1016/j.ejor.2012.09.004 PG 6 WC Management; Operations Research & Management Science SC Business & Economics; Operations Research & Management Science GA 039PZ UT WOS:000311260300013 ER PT J AU Singla, A O'Neill, JEB Smith, E Scott, RM AF Singla, Amit O'Neill, Jill E. Brace Smith, Edward Scott, R. Michael TI Cavernous malformations of the brain after treatment for acute lymphocytic leukemia: presentation and long-term follow-up Clinical article SO JOURNAL OF NEUROSURGERY-PEDIATRICS LA English DT Article DE cavernous malformation; radiation; surgery; acute lymphocytic leukemia; long-term follow-up; vascular disorders ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CENTRAL-NERVOUS-SYSTEM; NATURAL-HISTORY; CHILDHOOD; CHILDREN; THERAPY; IRRADIATION; HEMANGIOMAS; DIAGNOSIS; SURVIVORS AB Object. The authors undertook this study to determine the clinical course and long-term outcomes in pediatric patients who developed cavernous malformations of the brain following treatment for acute lymphocytic leukemia (ALL). Methods. They reviewed the senior author's database of surgically treated cavernous malformations of the brain to identify those patients whose cavernous malformations developed after cranial radiation during treatment for ALL. The medical records of these patients were reviewed to determine their clinical presentation, radiological findings, and outcome at long-term follow-up. Results. Five patients fulfilled the specified criteria over a 23-year period. At the time of ALL diagnosis, they were all 4-5 years old. The cerebral cavernous malformations developed 2-8 years after cranial radiation, and 4 of the 5 patients presented with neurological symptoms, which ranged from focal deficits to seizures. Two patients required a second craniotomy, one from lesion recurrence possibly due to incomplete resection, and another for a second cavernous malformation, which developed at another site 6 years after the initial malformation was excised. Long-term follow-up of 2,10,11,11, and 17 years has revealed no additional lesion development or recurrence. Conclusions. Symptomatic cavernous malformations of the brain may develop several years after chemotherapy and cranial radiation treatment for ALL, and the clinical course of these cavernous malformations may be more aggressive than that of the typical post-radiation lesions seen in other conditions. Long-term clinical and imaging monitoring is recommended for children who have undergone treatment for ALL. Craniotomy for excision of the malformations appears to convey long-term protection from repeat hemorrhage and accumulating neurological deficits. (http://thejns.org/doi/abs/10.3171/2012.11.PEDS12235) C1 [Singla, Amit] SUNY Upstate Med Univ, Dept Neurosurg, Syracuse, NY 13210 USA. [O'Neill, Jill E. Brace] Dana Farber Canc Inst, Boston, MA 02115 USA. [Smith, Edward; Scott, R. Michael] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. RP Scott, RM (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Neurosurg, 300 Longwood Ave,HU2, Boston, MA 02115 USA. EM michael.scott@childrens.harvard.edu NR 21 TC 4 Z9 4 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1933-0707 EI 1933-0715 J9 J NEUROSURG-PEDIATR JI J. Neurosurg.-Pediatr. PD FEB PY 2013 VL 11 IS 2 BP 127 EP 132 DI 10.3171/2012.11.PEDS12235 PG 6 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA 076DV UT WOS:000313937600006 PM 23215773 ER PT J AU Ginat, DT Prabhu, SP Madsen, JR AF Ginat, Daniel T. Prabhu, Sanjay P. Madsen, Joseph R. TI Postshunting corpus callosum swelling with depiction on tractography SO JOURNAL OF NEUROSURGERY-PEDIATRICS LA English DT Article DE corpus callosmn swelling; ventricle; hydrocephalus; ventricular decompression; magnetic resonance imaging; tractography ID HYDROCEPHALUS; LESIONS AB Alterations in the appearance of the corpus callosum occasionally occur following successful ventricular decompression in patients with chronic hydrocephalus. There are certain features on imaging that suggest the diagnosis of what the authors propose be termed "postshunting corpus callosum swelling," including diffuse high T2 signal predominantly affecting the body of the corpus callosum, with transverse orientation along the crossing white matter tracts and scalloping along the posterior margin of the structure. In this report, the authors demonstrate preservation of the corpus callosum white matter fiber tracts by using diffusion tensor imaging with tractography. (http://thejns.org/doi/abs/10.3171/2012.10.PEDS1242) C1 [Ginat, Daniel T.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Prabhu, Sanjay P.] Boston Childrens Hosp, Dept Radiol, Boston, MA USA. [Madsen, Joseph R.] Boston Childrens Hosp, Dept Neurosurg, Boston, MA USA. RP Ginat, DT (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM ginatd01@gmail.com NR 8 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1933-0707 EI 1933-0715 J9 J NEUROSURG-PEDIATR JI J. Neurosurg.-Pediatr. PD FEB PY 2013 VL 11 IS 2 BP 178 EP 180 DI 10.3171/2012.10.PEDS1242 PG 3 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA 076DV UT WOS:000313937600014 PM 23157395 ER PT J AU Wong, MH Johnson, MD AF Wong, Mandi H. Johnson, Meshell D. TI Differential Response of Primary Alveolar Type I and Type II Cells to LPS Stimulation SO PLOS ONE LA English DT Article ID SURFACTANT-PROTEIN-D; NF-KAPPA-B; ACUTE LUNG INJURY; EPITHELIAL-CELLS; PULMONARY SURFACTANT; PNEUMOCOCCAL PNEUMONIA; GENE-EXPRESSION; PRIMARY CULTURE; HOST-DEFENSE; TNF-ALPHA AB The alveolar epithelium serves as a barrier between organism and environment and functions as the first line of protection against potential respiratory pathogens. Alveolar type II (TII) cells have traditionally been considered the immune cells of the alveolar epithelium, as they possess immunomodulatory functions; however, the precise role of alveolar type I (TI) cells, which comprise similar to 95% of the alveolar epithelial surface area, in lung immunity is not clear. We sought to determine if there was a difference in the response of TI and TII cells to lung injury and if TI cells could actively participate in the alveolar immune response. TI cells isolated via fluorescence activated cell sorting (FACS) from LPS-injured rats demonstrated greater fold-induction of multiple inflammatory mediators than TII cells isolated in the same manner from the same animals. Levels of the cytokines TNF-alpha, IL-6 and IL-1 beta from cultured primary rat TI cells after LPS stimulation were significantly increased compared to similarly studied primary rat TII cells. We found that contrary to published reports, cultured TII cells produce relatively small amounts of TNF-alpha, IL-6 and IL-1 beta after LPS treatment; the higher levels of cytokine expression from cultured TII cells reported in the literature were likely from macrophage contamination due to traditional non-FACS TII cell isolation methods. Co-culture of TII cells with macrophages prior to LPS stimulation increased TNF-alpha and IL-6 production to levels reported by other investigators for TII cells, however, co-culture of TI cells and macrophages prior to LPS treatment resulted in marked increases in TNF-alpha and IL-6 production. Finally, exogenous surfactant blunted the IL-6 response to LPS in cultured TI cells. Taken together, these findings advocate a role for TI cells in the innate immune response and suggest that both TI and TII cells are active players in host defense mechanisms in the lung. C1 [Wong, Mandi H.; Johnson, Meshell D.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Wong, Mandi H.; Johnson, Meshell D.] No Calif Inst Res & Educ, San Francisco, CA USA. [Johnson, Meshell D.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Johnson, MD (reprint author), San Francisco VA Med Ctr, San Francisco, CA 94121 USA. EM meshell.johnson@ucsf.edu FU Department of Veterans Affairs [CDA2]; Northern California Institute for Research and Education FX This work was supported by grants from the Department of Veterans Affairs (CDA2) and the Northern California Institute for Research and Education (www.ncire.org). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 13 Z9 15 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 31 PY 2013 VL 8 IS 1 AR e55545 DI 10.1371/journal.pone.0055545 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 085JH UT WOS:000314610600124 PM 23383221 ER PT J AU Rubenstein, JL Li, J Chen, LJ Advani, R Drappatz, J Gerstner, E Batchelor, T Krouwer, H Hwang, J Auerback, G Kadoch, C Lowell, C Munster, P Cha, S Shuman, MA Damon, LE AF Rubenstein, James L. Li, Jing Chen, Lingjing Advani, Ranjana Drappatz, Jan Gerstner, Elizabeth Batchelor, Tracy Krouwer, Hendrikus Hwang, James Auerback, Glenna Kadoch, Cigall Lowell, Clifford Munster, Pamela Cha, Soonmee Shuman, Marc A. Damon, Lloyd E. TI Multicenter phase 1 trial of intraventricular immunochemotherapy in recurrent CNS lymphoma SO BLOOD LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; B-CELL LYMPHOMA; INTRATHECAL RITUXIMAB; NEUROTROPHIC FACTOR; ANTI-CD20 ANTIBODY; SURVIVAL; THERAPY; CHEMOTHERAPY; INVOLVEMENT; INCREASES AB Recurrent CNS lymphoma continues to be associated with poor outcomes in the rituximab era. Although IV rituximab mediates superior disease control of systemic non-Hodgkin lymphoma (NHL), it fails to completely eliminate the risk of meningeal recurrence, likely due to minimal CNS penetration. Given that rituximab acts synergistically with chemotherapy, we conducted the first phase 1 study of intraventricular immunochemotherapy in patients with recurrent CNS NHL. Fourteen patients received 10 mg or 25 mg intraventricular rituximab twice weekly for 4 weeks, with rituximab administered as monotherapy during the first treatment each week and rituximab administered in combination with methotrexate (MTX) during the second treatment each week. More than 150 doses were administered without serious toxicity. In a population with high-refractory CNS NHL, 75% of patients achieved complete cytologic responses and 43% achieved an overall complete response in CSF and/or brain parenchyma. Two patients achieved a first complete response of CNS NHL with intraventricular rituximab/MTX, including 1 with CNS lymphoma refractory to high-dose systemic and intrathecal MTX plus IV rituximab. We conclude that intraventricularrituximab in combination with MTX is feasible and highly active in the treatment of drug-resistant CNS NHL that is refractory or unresponsive to IV rituximab. This trial is registered at www.clinicaltrials.gov as NCT00221325. (Blood. 2013;121(5):745-751) C1 [Rubenstein, James L.; Chen, Lingjing; Auerback, Glenna; Kadoch, Cigall; Munster, Pamela; Shuman, Marc A.; Damon, Lloyd E.] Univ Calif San Francisco, Div Hematol Oncol, San Francisco, CA 94143 USA. [Rubenstein, James L.; Auerback, Glenna; Munster, Pamela; Cha, Soonmee; Shuman, Marc A.; Damon, Lloyd E.] Univ Calif San Francisco, Helen Diller Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Li, Jing] Genentech Inc, San Francisco, CA 94080 USA. [Advani, Ranjana] Stanford Univ, Stanford, CA 94305 USA. [Drappatz, Jan] Dana Farber Canc Ctr, Dept Neurooncol, Boston, MA USA. [Gerstner, Elizabeth; Batchelor, Tracy] Massachusetts Gen Hosp, Dept Neurooncol, Boston, MA 02114 USA. [Krouwer, Hendrikus] Med Coll Wisconsin, Dept Neurooncol, Milwaukee, WI 53226 USA. [Hwang, James] Univ Calif San Francisco, Biostat & Computat Biol Core, San Francisco, CA 94143 USA. [Lowell, Clifford] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. [Cha, Soonmee] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. RP Rubenstein, JL (reprint author), Univ Calif San Francisco, Div Hematol Oncol, M1282 Box 1270, San Francisco, CA 94143 USA. EM jamesr@medicine.ucsf.edu FU Leukemia & Lymphoma Society, a University of California; San Francisco Brain Tumor Specialized Programs of Research Excellence grant; Gabrielle's Angel Foundation; National Institutes of Health [R01CA139-83-01A1] FX This research was supported by the Leukemia & Lymphoma Society, a University of California, San Francisco Brain Tumor Specialized Programs of Research Excellence grant, Gabrielle's Angel Foundation, and the National Institutes of Health (grant R01CA139-83-01A1 to J.L.R.). NR 31 TC 32 Z9 33 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 31 PY 2013 VL 121 IS 5 BP 745 EP 751 DI 10.1182/blood-2012-07-440974 PG 7 WC Hematology SC Hematology GA 088WA UT WOS:000314867200007 PM 23197589 ER PT J AU Scaradavou, A Brunstein, CG Eapen, M Le-Rademacher, J Barker, JN Chao, N Cutler, C Delaney, C Kan, FY Isola, L Karanes, C Laughlin, MJ Wagner, JE Shpall, EJ AF Scaradavou, Andromachi Brunstein, Claudio G. Eapen, Mary Le-Rademacher, Jennifer Barker, Juliet N. Chao, Nelson Cutler, Corey Delaney, Colleen Kan, Fangyu Isola, Luis Karanes, Chatchada Laughlin, Mary J. Wagner, John E. Shpall, Elizabeth J. TI Double unit grafts successfully extend the application of umbilical cord blood transplantation in adults with acute leukemia SO BLOOD LA English DT Article ID STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; HEMATOLOGIC MALIGNANCY; BONE-MARROW; OUTCOMES; ENGRAFTMENT; RECIPIENTS; RISKS AB Cell dose is a major limitation for umbilical cord blood (UCB) transplantation because units containing a minimum of 2.5 x 10(7) total nucleated cells (TNC)/kilogram patient body weight are frequently not available. The transplantation of 2 partially HLA-matched UCB units has been adopted as a simple approach for increasing the TNC. We sought to determine whether the relative safety and efficacy of this approach was comparable with a single UCB transplantation. Included are adults with acute leukemia who received transplants with 1 (n = 106) or 2 (n = 303) UCB units. All UCB units for single UCB transplantations contained TNC >= 2.5 x 10(7)/kg. For double UCB transplantations, the total TNC for units 1 and 2 were > 2.5 x 10(7)/kg but in approximately half of these transplantations, 1 of the 2 units contained < 2.5 x 10(7) TNC/kg. Adjusting for factors associated with outcomes, risks of neutrophil recovery (odds ratio 0.83, P = .59), transplantation-related mortality (hazard ratio [HR] 0.91, P = .63), relapse (HR 0.90, P = .64), and overall mortality (HR 0.93, P = .62) was similar after double UCB and adequate dose single UCB transplantations. These data support double UCB unit transplantation for acute leukemia when an adequately dosed single UCB unit is not available thereby extending access to nearly all patients. (Blood. 2013; 121(5): 752-758) C1 [Scaradavou, Andromachi] New York Blood Ctr, New York, NY 10021 USA. [Brunstein, Claudio G.; Wagner, John E.] Univ Minnesota, Minneapolis, MN USA. [Eapen, Mary; Le-Rademacher, Jennifer; Kan, Fangyu] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Eapen, Mary] Med Coll Wisconsin, Dept Med, Div Hematol Oncol, Milwaukee, WI 53226 USA. [Le-Rademacher, Jennifer] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA. [Barker, Juliet N.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Chao, Nelson] Duke Univ, Med Ctr, Durham, NC USA. [Cutler, Corey] Dana Farber Canc Ctr, Boston, MA USA. [Delaney, Colleen] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Isola, Luis] Mt Sinai Med Ctr, New York, NY 10029 USA. [Karanes, Chatchada] City Hope Natl Med Ctr, Duarte, CA USA. [Laughlin, Mary J.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Shpall, Elizabeth J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Shpall, EJ (reprint author), Univ Texas MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM eshpall@mdanderson.org FU Public Health Service [U24-CA76518]; National Cancer Institute; National Heart, Lung, and Blood Institute; National Institute of Allergy and Infectious Diseases, Health Resources and Services Administration [HHSH234200637015C]; Office of Naval Research, Department of Navy to the National Marrow Donor Program [N00014-10-01-0204] FX This work was supported by a Public Health Service grant (U24-CA76518) from the National Cancer Institute, the National Heart, Lung, and Blood Institute, and the National Institute of Allergy and Infectious Diseases, Health Resources and Services Administration (HHSH234200637015C), and the Office of Naval Research, Department of Navy to the National Marrow Donor Program (N00014-10-01-0204). NR 30 TC 76 Z9 81 U1 0 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 31 PY 2013 VL 121 IS 5 BP 752 EP 758 DI 10.1182/blood-2012-08-449108 PG 7 WC Hematology SC Hematology GA 088WA UT WOS:000314867200008 PM 23223509 ER PT J AU Ndhlovu, ZM Chibnik, LB Proudfoot, J Vine, S McMullen, A Cesa, K Porichis, F Jones, RB Alvino, DM Hart, MG Stampouloglou, E Piechocka-Trocha, A Kadie, C Pereyra, F Heckerman, D De Jager, PL Walker, BD Kaufmann, DE AF Ndhlovu, Zaza M. Chibnik, Lori B. Proudfoot, Jacqueline Vine, Seanna McMullen, Ashley Cesa, Kevin Porichis, Filippos Jones, R. Brad Alvino, Donna Marie Hart, Meghan G. Stampouloglou, Eleni Piechocka-Trocha, Alicja Kadie, Carl Pereyra, Florencia Heckerman, David De Jager, Philip L. Walker, Bruce D. Kaufmann, Daniel E. TI High-dimensional immunomonitoring models of HIV-1-specific CD8 T-cell responses accurately identify subjects achieving spontaneous viral control SO BLOOD LA English DT Article ID LONG-TERM NONPROGRESSORS; IMMUNODEFICIENCY-VIRUS-REPLICATION; HIV-INFECTION; LYMPHOCYTE RESPONSE; ANTIRETROVIRAL THERAPY; IMMUNE CONTROL; PROLIFERATION; VIREMIA; ESCAPE; SUPPRESSION AB The development of immunomonitoring models to determine HIV-1 vaccine efficacy is a major challenge. Studies suggest that HIV-1-specific CD8 T cells play a critical role in subjects achieving spontaneous viral control (HIV-1 controllers) and that they will be important in immune interventions. However, no single CD8 T-cell function is uniquely associated with controller status and the heterogeneity of responses targeting different epitopes further complicates the discovery of determinants of protective immunity. In the present study, we describe immunomonitoring models integrating multiple functions of epitope-specific CD8 T cells that distinguish controllers from subjects with treated or untreated progressive infection. Models integrating higher numbers of variables and trained with the least absolute shrinkage and selection operator (LASSO) variant of logistic regression and 10-fold cross-validation produce "diagnostic tests" that display an excellent capacity to delineate subject categories. The test accuracy reaches 75% area under the receiving operating characteristic curve in cohorts matched for prevalence of protective alleles. Linear mixed-effects model analyses show that the proliferative capacity, cytokine production, and kinetics of cytokine secretion are associated with HIV-1 control. Although proliferative capacity is the strongest single discriminant, integrated modeling of different dimensions of data leverages individual associations. This strategy may have important applications in predictive model development and immune monitoring of HIV-1 vaccine trials. (Blood. 2013;121(5):801-811) C1 [Ndhlovu, Zaza M.; Proudfoot, Jacqueline; Vine, Seanna; McMullen, Ashley; Cesa, Kevin; Porichis, Filippos; Jones, R. Brad; Alvino, Donna Marie; Hart, Meghan G.; Stampouloglou, Eleni; Piechocka-Trocha, Alicja; Pereyra, Florencia; Walker, Bruce D.; Kaufmann, Daniel E.] Harvard Univ, Massachusetts Inst Technol & Harvard, Sch Med, Massachusetts Gen Hosp,Ragon Inst, Boston, MA USA. [Ndhlovu, Zaza M.; De Jager, Philip L.] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa. [Ndhlovu, Zaza M.; De Jager, Philip L.] Univ KwaZulu Natal, Nelson R Mandela Sch Med, KwaZulu Natal Res Inst, Durban, South Africa. [Chibnik, Lori B.] Brigham & Womens Hosp, Dept Neurol, Program Translat Neuropsychiat Genom, Inst Neurosci, Boston, MA 02115 USA. [Chibnik, Lori B.] Harvard Univ, Sch Med, Boston, MA USA. [Kadie, Carl] Microsoft Res, Redmond, WA USA. [Heckerman, David] Microsoft Res, Los Angeles, CA USA. [De Jager, Philip L.] Broad Inst Harvard Univ & Massachusetts Inst Tech, Cambridge, MA USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Walker, Bruce D.; Kaufmann, Daniel E.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Kaufmann, Daniel E.] Ctr Hosp Univ Montreal, Ctr Rech, Montreal, PQ, Canada. RP Kaufmann, DE (reprint author), Hop St Luc, Ctr Rech, Bur 304, CHUM, Pavillon Edouard Asselin,264,Blvd Rene Levesque E, Montreal, PQ H2X 1P1, Canada. EM dkaufmann@partners.org FU Ragon Institute; National Institute of Allergy and Infectious Diseases of the National Institutes of Health [RO1 AI30914, PO1 AI-080192]; National Heart, Lung, and Blood Institute of the National Institutes of Health [RO1 HL-092565]; Mark and Lisa Schwartz Foundation; Howard Hughes Medical Institute; Bill and Melinda Gates Foundation FX This study was supported by an Innovation Award of the Ragon Institute (to D.E.K. and P.L.D.J.), the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (RO1 AI30914 to B.D.W and PO1 AI-080192 to D.E.K.), the National Heart, Lung, and Blood Institute of the National Institutes of Health (RO1 HL-092565 to D.E.K.), the Mark and Lisa Schwartz Foundation (to B.D.W.), the Howard Hughes Medical Institute (to B.D.W.), and the Bill and Melinda Gates Foundation (to F. Pereyra and B.D.W.). NR 52 TC 22 Z9 22 U1 1 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 31 PY 2013 VL 121 IS 5 BP 801 EP 811 DI 10.1182/blood-2012-06-436295 PG 11 WC Hematology SC Hematology GA 088WA UT WOS:000314867200013 PM 23233659 ER PT J AU Voorhees, PM Laubach, J Anderson, KC Richardson, PG AF Voorhees, Peter M. Laubach, Jacob Anderson, Kenneth C. Richardson, Paul G. TI Peripheral neuropathy in multiple myeloma patients receiving lenalidomide, bortezomib, and dexamethasone (RVD) therapy SO BLOOD LA English DT Letter C1 [Voorhees, Peter M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Div Hematol Oncol, Chapel Hill, NC 27599 USA. [Laubach, Jacob; Anderson, Kenneth C.; Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Laubach, Jacob; Anderson, Kenneth C.; Richardson, Paul G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. RP Voorhees, PM (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Phys Off Bldg,170 Manning Dr, Chapel Hill, NC 27599 USA. EM peter_voorhees@med.unc.edu FU NCI NIH HHS [P01 CA078378, P01 CA155258, P50 CA100707] NR 8 TC 4 Z9 4 U1 0 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 31 PY 2013 VL 121 IS 5 BP 858 EP 858 DI 10.1182/blood-2012-11-465765 PG 1 WC Hematology SC Hematology GA 088WA UT WOS:000314867200019 PM 23372151 ER PT J AU Alt, FW Zhang, Y Meng, FL Guo, CG Schwer, B AF Alt, Frederick W. Zhang, Yu Meng, Fei-Long Guo, Chunguang Schwer, Bjoern TI Mechanisms of Programmed DNA Lesions and Genomic Instability in the Immune System SO CELL LA English DT Review ID CLASS-SWITCH RECOMBINATION; DOUBLE-STRAND BREAKS; RECURRENT CHROMOSOMAL TRANSLOCATIONS; END-JOINING PATHWAY; B-CELL DEVELOPMENT; V(D)J RECOMBINATION; IGH LOCUS; SOMATIC HYPERMUTATION; HOMOLOGOUS RECOMBINATION; ANTISENSE TRANSCRIPTION AB Chromosomal translocations involving antigen receptor loci are common in lymphoid malignancies. Translocations require DNA double-strand breaks (DSBs) at two chromosomal sites, their physical juxtaposition, and their fusion by end-joining. Ability of lymphocytes to generate diverse repertoires of antigen receptors and effector antibodies derives from programmed genomic alterations that produce DSBs. We discuss these lymphocyte-specific processes, with a focus on mechanisms that provide requisite DSB target specificity and mechanisms that suppress DSB translocation. We also discuss recent work that provides new insights into DSB repair pathways and the influences of three-dimensional genome organization on physiological processes and cancer genomes. C1 [Alt, Frederick W.; Zhang, Yu; Meng, Fei-Long; Guo, Chunguang; Schwer, Bjoern] Howard Hughes Med Inst, Boston, MA 02115 USA. [Alt, Frederick W.; Zhang, Yu; Meng, Fei-Long; Guo, Chunguang; Schwer, Bjoern] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Alt, Frederick W.; Zhang, Yu; Meng, Fei-Long; Guo, Chunguang; Schwer, Bjoern] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Alt, Frederick W.; Zhang, Yu; Meng, Fei-Long; Guo, Chunguang; Schwer, Bjoern] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Alt, FW (reprint author), Howard Hughes Med Inst, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu FU NIH/NIA [K01AG043630]; NIH; Leukemia and Lymphoma Society of America Marshall A. Lichtman Specialized Center of Research Grant [7009-121]; Howard Hughes Medical Institute Investigator FX We thank Andre Nussenzweig, Duane Wesemann, and David Weinstock for helpful comments. As this Review cites only primary publications from the past 5 years, we apologize that space restrictions make it impossible to cite all relevant publications. However, for each area covered, we cite very recent reviews in which additional details and references can be found. F.M. and C.G. are supported by Cancer Research Institute Fellowships, and B.S. is supported by NIH/NIA grant K01AG043630. F.W.A. is supported by NIH grants and a Leukemia and Lymphoma Society of America Marshall A. Lichtman Specialized Center of Research Grant (7009-121), and he is a Howard Hughes Medical Institute Investigator. NR 99 TC 137 Z9 140 U1 4 U2 37 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JAN 31 PY 2013 VL 152 IS 3 BP 417 EP 429 DI 10.1016/j.cell.2013.01.007 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 081ZZ UT WOS:000314362800013 PM 23374339 ER PT J AU Li, QY Seo, JH Stranger, B McKenna, A Pe'er, I LaFramboise, T Brown, M Tyekucheva, S Freedman, ML AF Li, Qiyuan Seo, Ji-Heui Stranger, Barbara McKenna, Aaron Pe'er, Itsik LaFramboise, Thomas Brown, Myles Tyekucheva, Svitlana Freedman, Matthew L. TI Integrative eQTL-Based Analyses Reveal the Biology of Breast Cancer Risk Loci SO CELL LA English DT Article ID ALLELIC EXPRESSION IMBALANCE; LONG-RANGE INTERACTION; GENOME-WIDE ANALYSIS; GENE-EXPRESSION; REGULATORY VARIATION; COLORECTAL-CANCER; CHOLESTEROL LOCUS; FGFR2 EXPRESSION; CELLS; CIS AB Germline determinants of gene expression in tumors are infrequently studied due to the complexity of transcript regulation caused by somatically acquired alterations. We performed expression quantitative trait locus (eQTL)-based analyses using the multi-level information provided in The Cancer Genome Atlas (TCGA). Of the factors we measured, cis-acting eQTLs accounted for 1.2% of the total variation of tumor gene expression, while somatic copy-number alteration and CpG methylation accounted for 7.3% and 3.3%, respectively. eQTL analyses of 15 previously reported breast cancer risk loci resulted in the discovery of three variants that are significantly associated with transcript levels (false discovery rate [FDR] < 0.1). Our trans-based analysis identified an additional three risk loci to act through ESR1, MYC, and KLF4. These findings provide a more comprehensive picture of gene expression determinants in breast cancer as well as insights into the underlying biology of breast cancer risk loci. C1 [Li, Qiyuan; Seo, Ji-Heui; Brown, Myles; Freedman, Matthew L.] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Dept Med Oncol, Boston, MA 02215 USA. [Li, Qiyuan; Seo, Ji-Heui; Freedman, Matthew L.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02215 USA. [Tyekucheva, Svitlana] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Li, Qiyuan; Freedman, Matthew L.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [McKenna, Aaron] Broad Inst, Canc Program, Cambridge, MA 02142 USA. [Stranger, Barbara] Harvard Univ, Div Genet, Dept Med, Sch Med, Boston, MA 02115 USA. [Stranger, Barbara] Brigham & Womens Hosp, Boston, MA 02115 USA. [McKenna, Aaron] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Pe'er, Itsik] Columbia Univ, Dept Comp Sci, New York, NY 10027 USA. [LaFramboise, Thomas] Case Western Reserve Univ, Dept Genet & Genome Sci, Cleveland, OH 44106 USA. [Tyekucheva, Svitlana] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. RP Freedman, ML (reprint author), Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Dept Med Oncol, Boston, MA 02215 USA. EM freedman@broadinstitute.org OI Brown, Myles/0000-0002-8213-1658; Stranger, Barbara/0000-0001-9021-7331 FU Howard Hughes Medical Institute Physician-Scientist Early Career Awardee; Claudia Adams Barr award; U.S. National Institutes of Health (NIH) [ELLIPSE/GAME-ON-U19 CA148537, R01 CA131341]; Mayer Foundation; H.L. Snyder Medical Foundation; Kohlberg Foundation; A. David Mazzone Awards Program FX We thank Dr. Giovanni Parmigiani for his suggestions with respect to the statistical modeling. We thank Dr. Gad Getz for suggestions on data processing. M.L.F. is a Howard Hughes Medical Institute Physician-Scientist Early Career Awardee (www.hhmi.org) and a recipient of a 2009 Claudia Adams Barr award (www.dana-farber.org). This work was supported by grants from the U.S. National Institutes of Health (NIH) (ELLIPSE/GAME-ON-U19 CA148537 to M.L.F. and R01 CA131341 to T.L. and I.P.), the Mayer Foundation (to M.L.F.), the H.L. Snyder Medical Foundation (to M.L.F.), the Kohlberg Foundation, and the A. David Mazzone Awards Program (to M.L.F.). NR 47 TC 116 Z9 118 U1 2 U2 39 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JAN 31 PY 2013 VL 152 IS 3 BP 633 EP 641 DI 10.1016/j.cell.2012.12.034 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 081ZZ UT WOS:000314362800030 PM 23374354 ER PT J AU Zhu, J Adli, M Zou, JY Verstappen, G Coyne, M Zhang, XL Durham, T Miri, M Deshpande, V De Jager, PL Bennett, DA Houmard, JA Muoio, DM Onder, TT Camahort, R Cowan, CA Meissner, A Epstein, CB Shoresh, N Bernstein, BE AF Zhu, Jiang Adli, Mazhar Zou, James Y. Verstappen, Griet Coyne, Michael Zhang, Xiaolan Durham, Timothy Miri, Mohammad Deshpande, Vikram De Jager, Philip L. Bennett, David A. Houmard, Joseph A. Muoio, Deborah M. Onder, Tamer T. Camahort, Ray Cowan, Chad A. Meissner, Alexander Epstein, Charles B. Shoresh, Noam Bernstein, Bradley E. TI Genome-wide Chromatin State Transitions Associated with Developmental and Environmental Cues SO CELL LA English DT Article ID PLURIPOTENT STEM-CELLS; EPIGENETIC SIGNATURE; ORGANIZATION; SENESCENCE; PLASTICITY; ENHANCERS; DYNAMICS; REVEALS; COMPLEX; IMPACT AB Differences in chromatin organization are key to the multiplicity of cell states that arise from a single genetic background, yet the landscapes of in vivo tissues remain largely uncharted. Here, we mapped chromatin genome-wide in a large and diverse collection of human tissues and stem cells. The maps yield unprecedented annotations of functional genomic elements and their regulation across developmental stages, lineages, and cellular environments. They also reveal global features of the epigenome, related to nuclear architecture, that also vary across cellular phenotypes. Specifically, developmental specification is accompanied by progressive chromatin restriction as the default state transitions from dynamic remodeling to generalized compaction. Exposure to serum in vitro triggers a distinct transition that involves de novo establishment of domains with features of constitutive heterochromatin. We describe how these global chromatin state transitions relate to chromosome and nuclear architecture, and discuss their implications for lineage fidelity, cellular senescence, and reprogramming. C1 [Zhu, Jiang; Adli, Mazhar; Zou, James Y.; Verstappen, Griet; Coyne, Michael; Zhang, Xiaolan; Durham, Timothy; De Jager, Philip L.; Camahort, Ray; Cowan, Chad A.; Meissner, Alexander; Epstein, Charles B.; Shoresh, Noam; Bernstein, Bradley E.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Zhu, Jiang; Adli, Mazhar; Zou, James Y.; Bernstein, Bradley E.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Zhu, Jiang; Adli, Mazhar; Zou, James Y.; Miri, Mohammad; Deshpande, Vikram; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Zhu, Jiang; Adli, Mazhar; Zou, James Y.; Miri, Mohammad; Deshpande, Vikram; Bernstein, Bradley E.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Zhu, Jiang; Adli, Mazhar; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Zhu, Jiang; Adli, Mazhar; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Zou, James Y.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Verstappen, Griet; Camahort, Ray; Cowan, Chad A.; Meissner, Alexander] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [De Jager, Philip L.] Brigham & Womens Hosp, Program Translat NeuroPsychiat Genom, Inst Neurosci, Dept Neurol, Boston, MA 02215 USA. [De Jager, Philip L.] Brigham & Womens Hosp, Program Translat NeuroPsychiat Genom, Inst Neurosci, Dept Psychiat, Boston, MA 02215 USA. [De Jager, Philip L.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Houmard, Joseph A.] E Carolina Univ, Dept Exercise & Sport Sci, Greenville, NC 27858 USA. [Muoio, Deborah M.] Duke Univ, Sch Med, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. [Onder, Tamer T.] Koc Univ, Sch Med, Istanbul, Turkey. RP Adli, M (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. EM adli@virginia.edu; bernstein.bradley@mgh.harvard.edu RI Zhu, Jiang/E-3049-2013; Onder, Tamer /H-3330-2013; Muoio, Debbie/E-1147-2012 OI Onder, Tamer /0000-0002-2372-9158; FU NIH Common Fund [U01 ES017155]; National Human Genome Research Institute [U54 HG004570]; National Heart, Lung and Blood Institute [U01 HL100395]; National Institute on Aging [P30 AG10161]; Howard Hughes Medical Institute; Starr Cancer Consortium; Burroughs Wellcome Fund FX We acknowledge members of the Broad Institute's Epigenomics Program and Genome Sequencing and Analysis Program, and the NIH Epigenomics Mapping Consortium for constructive comments. We thank Kevin Eggan for ES and iPS lines; Allen Powe and Steve Stice for neural cells; Greg Lauwers and the MGH Tissue Repository for tissue procurement; and David Flowers, Irwin Bernstein, John Stamatoyannopoulos and Shelly Heimfeld for blood samples. We also thank Leslie Gaffney and Lauren Solomon for assistance with figures. This research was supported by the NIH Common Fund (U01 ES017155); the National Human Genome Research Institute (U54 HG004570); the National Heart, Lung and Blood Institute (U01 HL100395); the National Institute on Aging (P30 AG10161); the Howard Hughes Medical Institute; the Starr Cancer Consortium; and the Burroughs Wellcome Fund. NR 42 TC 216 Z9 218 U1 6 U2 100 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 31 PY 2013 VL 152 IS 3 BP 642 EP 654 DI 10.1016/j.cell.2012.12.033 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 081ZZ UT WOS:000314362800031 PM 23333102 ER PT J AU Tabach, Y Billi, AC Hayes, GD Newman, MA Zuk, O Gabel, H Kamath, R Yacoby, K Chapman, B Garcia, SM Borowsky, M Kim, JK Ruvkun, G AF Tabach, Yuval Billi, Allison C. Hayes, Gabriel D. Newman, Martin A. Zuk, Or Gabel, Harrison Kamath, Ravi Yacoby, Keren Chapman, Brad Garcia, Susana M. Borowsky, Mark Kim, John K. Ruvkun, Gary TI Identification of small RNA pathway genes using patterns of phylogenetic conservation and divergence SO NATURE LA English DT Article ID C-ELEGANS; SYSTEMATIC IDENTIFICATION; PROTEINS; INTERFERENCE; POLYMERASE; PROFILES; COMPLEX; YEAST; DCR-1; SIRNA AB Genetic and biochemical analyses of RNA interference (RNAi) and microRNA (miRNA) pathways have revealed proteins such as Argonaute and Dicer as essential cofactors that process and present small RNAs to their targets. Well-validated small RNA pathway cofactors such as these show distinctive patterns of conservation or divergence in particular animal, plant, fungal and protist species. We compared 86 divergent eukaryotic genome sequences to discern sets of proteins that show similar phylogenetic profiles with known small RNA cofactors. A large set of additional candidate small RNA cofactors have emerged from functional genomic screens for defects in miRNA-or short interfering RNA (siRNA)-mediated repression in Caenorhabditis elegans and Dro-sophila melanogaster(1,2), and from proteomic analyses of proteins co-purifying with validated small RNA pathway proteins(3,4). The phylogenetic profiles of many of these candidate small RNA pathway proteins are similar to those of known small RNA cofactor proteins. We used a Bayesian approach to integrate the phylogenetic profile analysis with predictions from diverse transcriptional coregulation and proteome interaction data sets to assign a probability for each protein for a role in a small RNA pathway. Testing high-confidence candidates from this analysis for defects in RNAi silencing, we found that about one-half of the predicted small RNA cofactors are required for RNAi silencing. Many of the newly identified small RNA pathway proteins are orthologues of proteins implicated in RNA splicing. In support of a deep connection between the mechanism of RNA splicing and small-RNA-mediated gene silencing, the presence of the Argonaute proteins and other small RNA components in the many species analysed strongly correlates with the number of introns in those species. C1 [Tabach, Yuval; Hayes, Gabriel D.; Newman, Martin A.; Gabel, Harrison; Kamath, Ravi; Yacoby, Keren; Chapman, Brad; Garcia, Susana M.; Borowsky, Mark; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Tabach, Yuval; Hayes, Gabriel D.; Newman, Martin A.; Gabel, Harrison; Kamath, Ravi; Garcia, Susana M.; Borowsky, Mark; Ruvkun, Gary] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Billi, Allison C.; Kim, John K.] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. [Billi, Allison C.; Kim, John K.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. [Zuk, Or] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu OI Chapman, Brad/0000-0002-3026-1856 FU NIH [GM088565, GM44619, GM098647]; Pew Charitable Trusts FX We thank T. Duchaine for access to his ERI-1 proteomic data before it was published and to S. Fischer, C. Zhang and T. Montgomery for helpful discussions. The work was supported by NIH GM088565 and the Pew Charitable Trusts (J.K.K.) and NIH GM44619 and GM098647 (G.R.). NR 28 TC 42 Z9 43 U1 3 U2 116 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 31 PY 2013 VL 493 IS 7434 BP 694 EP 698 DI 10.1038/nature11779 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 080CU UT WOS:000314219600061 PM 23364702 ER PT J AU Weeks, JC Mack, JW Schrag, D AF Weeks, Jane C. Mack, Jennifer W. Schrag, Deborah TI Talking with Patients about Dying SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Weeks, Jane C.; Mack, Jennifer W.; Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Weeks, JC (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 1 U2 1 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 31 PY 2013 VL 368 IS 5 BP 480 EP 481 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 080BE UT WOS:000314215400025 PM 23363507 ER PT J AU Pallais, JC AF Pallais, J. Carl TI Case 33-2012: A Woman with Altered Mental Status after Childbirth Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID C-PEPTIDE; HYPOGLYCEMIA; PROINSULIN C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Pallais, JC (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 5 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 31 PY 2013 VL 368 IS 5 BP 487 EP 487 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 080BE UT WOS:000314215400036 PM 23363520 ER PT J AU Greka, A Bhatia, RS Sabir, SH Dekker, JP AF Greka, Anna Bhatia, R. Sacha Sabir, Sharjeel H. Dekker, John P. TI Case 4-2013: A 50-Year-Old Man with Acute Flank Pain SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACUTE RENAL INFARCTION; ACUTE LOIN PAIN; FIBROMUSCULAR DYSPLASIA; CLINICAL CHARACTERISTICS; POSTSPLENECTOMY SEPSIS; ATRIAL-FIBRILLATION; ARTERIES; BABESIOSIS; EMBOLISM C1 [Greka, Anna; Bhatia, R. Sacha] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Sabir, Sharjeel H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Dekker, John P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Greka, Anna; Bhatia, R. Sacha] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Sabir, Sharjeel H.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Dekker, John P.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Greka, A (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 21 TC 1 Z9 1 U1 1 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 31 PY 2013 VL 368 IS 5 BP 466 EP 472 DI 10.1056/NEJMcpc1201414 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 080BE UT WOS:000314215400013 PM 23343037 ER PT J AU Bush, G Holmes, J Shin, LM Surman, C Makris, N Mick, E Seidman, LJ Biederman, J AF Bush, George Holmes, Jennifer Shin, Lisa M. Surman, Craig Makris, Nikos Mick, Eric Seidman, Larry J. Biederman, Joseph TI Atomoxetine increases fronto-parietal functional MRI activation in attention-deficit/hyperactivity disorder: A pilot study SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Neuroimaging; Psychopharmacology; Neurobiology ID MULTISOURCE INTERFERENCE TASK; NOREPINEPHRINE TRANSPORTER; HEALTHY-VOLUNTEERS; METHYLPHENIDATE; PLACEBO; ADULTS; EFFICACY; HUMANS; SAFETY; TRIAL AB We hypothesized that atomoxetine (ATMX) would produce similar brain effects in attention-deficit/hyperactivity disorder (ADHD) as those of methylphenidate (MPH). Eleven ADHD adults performed the Multi-Source Interference Task (MSIT) during functional magnetic resonance imaging (fMRI) at baseline and after 6weeks of ATMX treatment. ATMX was associated with increased fMRI activation of dorsolateral prefrontal cortex, parietal cortex and cerebellum but not dorsal anterior midcingulate cortex (daMCC). These results suggest that ATMX and MPH have similar but not identical brain effects. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Bush, George; Surman, Craig; Mick, Eric; Seidman, Larry J.; Biederman, Joseph] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Bush, George; Holmes, Jennifer; Shin, Lisa M.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat Neurosci Div, Boston, MA 02114 USA. [Bush, George] Harvard Univ, Sch Med, Massachusetts Inst Technol,Massachusetts Gen Hosp, MGH MIT HMS Athinoula A Martinos Ctr Funct & Stru, Charlestown, MA 02129 USA. [Bush, George; Surman, Craig; Makris, Nikos; Mick, Eric; Seidman, Larry J.; Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Shin, Lisa M.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Makris, Nikos] Harvard Univ, Sch Med, Dept Neurol, Ctr Morphometr Anal,Massachusetts Gen Hosp, Boston, MA 02129 USA. [Makris, Nikos] Harvard Univ, Sch Med, Dept Radiol Serv, Ctr Morphometr Anal,Massachusetts Gen Hosp, Boston, MA 02129 USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat,Publ Psychiat Div,Beth Israel Deaco, Boston, MA 02115 USA. RP Biederman, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin & Res Program Pediat Psychopharmacol, 55 Fruit St,Warren 705, Boston, MA 02114 USA. EM jbiederman@partners.org OI Mick, Eric/0000-0001-8505-8145 FU Eli Lilly Company; Benson-Henry Institute at MGH for Mind-Body Medicine; Pediatric Psychopharmacology Council Fund; David Judah Fund; Mental Illness and Neuroscience Discovery (MIND) Institute FX Grant support was provided by Eli Lilly & Company, the Benson-Henry Institute at MGH for Mind-Body Medicine, the Pediatric Psychopharmacology Council Fund, the David Judah Fund, and the Mental Illness and Neuroscience Discovery (MIND) Institute. General support for the investigators and/or for the clinical studies from which subjects were ascertained was also Gilbert, 1997). For example, Versace et al. (2012) found that smokers with blunted cue reactivity to positive images were at higher risk for relapse than smokers with higher reactivity to positive stimuli. Future research should continue to identify individual factors that influence smoking-related behavioral outcomes. Better characterization of the individual personality measures associated with cue reactivity and relapse could lead to more efficacious forms of treatment for substance dependence. NR 26 TC 12 Z9 12 U1 0 U2 11 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD JAN 30 PY 2013 VL 211 IS 1 BP 88 EP 91 DI 10.1016/j.pscychresns.2012.09.004 PG 4 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 115QY UT WOS:000316828200013 PM 23146254 ER PT J AU Banigan, MG Kao, PF Kozubek, JA Winslow, AR Medina, J Costa, J Schmitt, A Schneider, A Cabral, H Cagsal-Getkin, O Vanderburg, CR Delalle, I AF Banigan, Meredith G. Kao, Patricia F. Kozubek, James A. Winslow, Ashley R. Medina, Juan Costa, Joan Schmitt, Andrea Schneider, Anja Cabral, Howard Cagsal-Getkin, Ozge Vanderburg, Charles R. Delalle, Ivana TI Differential Expression of Exosomal microRNAs in Prefrontal Cortices of Schizophrenia and Bipolar Disorder Patients SO PLOS ONE LA English DT Article ID FALSE DISCOVERY RATE; SHRUNKEN CENTROIDS; DENDRITIC SPINES; GENE-EXPRESSION; AMYLOID-BETA; BRAIN; PATHWAY; SECRETION; RNA; MICROARRAYS AB Exosomes are cellular secretory vesicles containing microRNAs (miRNAs). Once secreted, exosomes are able to attach to recipient cells and release miRNAs potentially modulating the function of the recipient cell. We hypothesized that exosomal miRNA expression in brains of patients diagnosed with schizophrenia (SZ) and bipolar disorder (BD) might differ from controls, reflecting either disease-specific or common aberrations in SZ and BD patients. The sources of the analyzed samples included McLean 66 Cohort Collection (Harvard Brain Tissue Resource Center), BrainNet Europe II (BNE, a consortium of 18 brain banks across Europe) and Boston Medical Center (BMC). Exosomal miRNAs from frozen postmortem prefrontal cortices with well-preserved RNA were isolated and submitted to profiling by Luminex FLEXMAP 3D microfluidic device. Multiple statistical analyses of microarray data suggested that certain exosomal miRNAs were differentially expressed in SZ and BD subjects in comparison to controls. RT-PCR validation confirmed that two miRNAs, miR-497 in SZ samples and miR-29c in BD samples, have significantly increased expression when compared to control samples. These results warrant future studies to evaluate the potential of exosome-derived miRNAs to serve as biomarkers of SZ and BD. C1 [Banigan, Meredith G.; Kao, Patricia F.; Delalle, Ivana] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA. [Banigan, Meredith G.; Cagsal-Getkin, Ozge; Vanderburg, Charles R.] Harvard NeuroDiscovery Ctr, Adv Tissue Resource Ctr, Charlestown, MA USA. [Kozubek, James A.] Boston Univ, Sch Med, Dept Biomed Genet, Boston, MA 02118 USA. [Winslow, Ashley R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Medina, Juan; Costa, Joan] Neurol Tissue Bank, Barcelona, Spain. [Schmitt, Andrea] Univ Munich, Dept Psychiat, D-80539 Munich, Germany. [Schmitt, Andrea] Univ Sao Paulo, Fac Med, Dept Psychiat, Neurosci Lab, Sao Paulo, Brazil. [Schmitt, Andrea] Univ Sao Paulo, Fac Med, Inst Psychiat, Sao Paulo, Brazil. [Schneider, Anja] Univ Med Goettingen, Dept Psychiat, Gottingen, Germany. [Schneider, Anja] German Res Ctr Neurodegenerat Dis, Gottingen, Germany. [Cabral, Howard] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [Cabral, Howard] Boston Univ, Clin & Translat Sci Inst, Boston, MA 02118 USA. RP Delalle, I (reprint author), Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA. EM idelalle@bu.edu OI Cabral, Howard/0000-0002-1185-8331 FU National Institute of Mental Health [R21 MH086079]; National Institute of Aging [T32 AG00015-21] FX This work was supported by the National Institute of Mental Health (R21 MH086079; ID and CRV) and National Institute of Aging (T32 AG00015-21; PFK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 67 TC 48 Z9 51 U1 2 U2 28 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 30 PY 2013 VL 8 IS 1 AR e48814 DI 10.1371/journal.pone.0048814 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 098QM UT WOS:000315563800002 PM 23382797 ER PT J AU Hirata, H Ueno, K Shahryari, V Deng, GR Tanaka, Y Tabatabai, ZL Hinoda, Y Dahiya, R AF Hirata, Hiroshi Ueno, Koji Shahryari, Varahram Deng, Guoren Tanaka, Yuichiro Tabatabai, Z. Laura Hinoda, Yuji Dahiya, Rajvir TI MicroRNA-182-5p Promotes Cell Invasion and Proliferation by Down Regulating FOXF2, RECK and MTSS1 Genes in Human Prostate Cancer SO PLOS ONE LA English DT Article ID SUPPRESSOR GENE; TARGETING RECK; METASTASIS; CARCINOMA; MIR-182; PROGRESSION; EXPRESSION; METALLOPROTEINASE; OVEREXPRESSION; AGGRESSIVENESS AB Recently miR-182 has been reported to be over-expressed in prostate cancer (PC) tissues, however detailed functional analysis of miR-182-5p has not been carried out. The purpose of this study was to: 1. analyze the function of miR-182-5p in prostate cancer, 2. assess its usefulness as a tumor marker, 3. identify miR-182-5p target genes in PC, 4. investigate the potential for miR-182-5p inhibitor to be used in PC treatment. Initially we found that miR-182-5p expression was significantly higher in prostate cancer tissues and cell lines compared to normal prostate tissues and cells. Moreover high miR-182-5p expression was associated with shorter overall survival in PC patients. To study the functional significance of miR-182-5p, we knocked down miR-182-5p with miR-182-5p inhibitor. After miR-182-5p knock-down, prostate cancer cell proliferation, migration and invasion were decreased. We identified FOXF2, RECK and MTSS1 as potential target genes of miR-182-5p using several algorithms which was confirmed by 3'UTR luciferase assay and Western analysis. Knock-down of miR-182-5p also significantly decreased in vivo prostate tumor growth. In conclusion this is the first report documenting that over-expression of miR-182-5p is associated with prostate cancer progression and potentially useful as a prognostic biomarker. Also knock down of miR-182-5p in order to increase expression of tumor suppressor genes FOXF2, RECK and MTSS1 may be of therapeutic benefit in prostate cancer treatment. C1 [Hirata, Hiroshi; Ueno, Koji; Shahryari, Varahram; Deng, Guoren; Tanaka, Yuichiro; Dahiya, Rajvir] San Francisco VA Med Ctr, Dept Urol, San Francisco, CA USA. [Hirata, Hiroshi; Ueno, Koji; Shahryari, Varahram; Deng, Guoren; Tanaka, Yuichiro; Tabatabai, Z. Laura; Dahiya, Rajvir] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Tabatabai, Z. Laura] San Francisco VA Med Ctr, Dept Pathol, San Francisco, CA USA. [Hinoda, Yuji] Yamaguchi Univ, Dept Oncol & Lab Med, Grad Sch Med, Yamaguchi, Japan. RP Dahiya, R (reprint author), San Francisco VA Med Ctr, Dept Urol, San Francisco, CA USA. EM rdahiya@urology.ucsf.edu FU National Center for Research Resources of the National Institutes of Health [RO1CA138642, RO1CA130860, RO1CA160079]; VA Merit Review grants; VA Program Project; Yamada Science Foundation FX This study was supported by National Center for Research Resources of the National Institutes of Health through Grant Number RO1CA138642, RO1CA130860, RO1CA160079, VA Merit Review grants, VA Program Project and Yamada Science Foundation. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. NR 36 TC 53 Z9 57 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 30 PY 2013 VL 8 IS 1 AR e55502 DI 10.1371/journal.pone.0055502 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 098QM UT WOS:000315563800161 PM 23383207 ER PT J AU Lee, BH Gauna, AE Perez, G Park, YJ Pauley, KM Kawai, T Cha, S AF Lee, Byung Ha Gauna, Adrienne E. Perez, Geidys Park, Yun-Jong Pauley, Kaleb M. Kawai, Toshihisa Cha, Seunghee TI Autoantibodies against Muscarinic Type 3 Receptor in Sjogren's Syndrome Inhibit Aquaporin 5 Trafficking SO PLOS ONE LA English DT Article ID APICAL PLASMA-MEMBRANE; 2ND EXTRACELLULAR LOOP; SALIVARY ACINAR-CELLS; ACETYLCHOLINE-RECEPTOR; WATER CHANNEL; ABNORMAL DISTRIBUTION; SUBMANDIBULAR-GLANDS; MOUSE MODEL; HSG CELLS; NOD MICE AB Sjogren's syndrome (SjS) is a chronic autoimmune disease that mainly targets the salivary and lacrimal glands. It has been controversial whether anti-muscarinic type 3 receptor (alpha-M3R) autoantibodies in patients with SjS inhibit intracellular trafficking of aquaporin-5 (AQP5), water transport protein, leading to secretory dysfunction. To address this issue, GFP-tagged human AQP5 was overexpressed in human salivary gland cells (HSG-hAQP5) and monitored AQP5 trafficking to the plasma membrane following carbachol (CCh, M3R agonist) stimulation. AQP5 trafficking was indeed mediated by M3R stimulation, shown in partial blockage of trafficking by M3R-antagonist 4-DAMP. HSG-hAQP5 pre-incubated with SjS plasma for 24 hours significantly reduced AQP5 trafficking with CCh, compared with HSG-hAQP5 pre-incubated with healthy control (HC) plasma. This inhibition was confirmed by monoclonal a-M3R antibody and pre-absorbed plasma. Interestingly, HSG-hAQP5 pre-incubated with SjS plasma showed no change in cell volume, compared to the cells incubated with HC plasma showing shrinkage by twenty percent after CCh-stimulation. Our findings clearly indicate that binding of anti-M3R autoantibodies to the receptor, which was verified by immunoprecipitation, suppresses AQP5 trafficking to the membrane and contribute to impaired fluid secretion in SjS. Our current study urges further investigations of clinical associations between SjS symptoms, such as degree of secretory dysfunction, cognitive impairment, and/or bladder irritation, and different profiles (titers, isotypes, and/or specificity) of anti-M3R autoantibodies in individuals with SjS. C1 [Lee, Byung Ha; Gauna, Adrienne E.; Perez, Geidys; Park, Yun-Jong; Cha, Seunghee] Univ Florida, Coll Dent, Dept Oral & Maxillofacial Diagnost Sci, Gainesville, FL 32610 USA. [Pauley, Kaleb M.] Cedarville Univ, Coll Arts & Sci, Dept Sci & Math, Cedarville, OH USA. [Kawai, Toshihisa] Forsyth Inst, Dept Immunol, Cambridge, MA USA. RP Cha, S (reprint author), Univ Florida, Coll Dent, Dept Oral & Maxillofacial Diagnost Sci, Gainesville, FL 32610 USA. EM scha@dental.ufl.edu FU NIH/NIDCR [DE019644, DE 016705]; [UL1 RR029890]; [TL1 RR029889]; [T90 DE021990] FX S.CHA was supported by NIH/NIDCR grants DE019644 and DE 016705. The funders had no role in study design, data c S.CHA was supported by NIH/NIDCR grants DE019644 and DE 016705. AE.GAUNA was supported by UL1 RR029890, TL1 RR029889, and T90 DE021990. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 43 TC 19 Z9 20 U1 2 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 30 PY 2013 VL 8 IS 1 AR e53113 DI 10.1371/journal.pone.0053113 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 098QM UT WOS:000315563800018 PM 23382834 ER PT J AU Vandenberghe, LH Bell, P Maguire, AM Xiao, R Hopkins, TB Grant, R Bennett, J Wilson, JM AF Vandenberghe, Luk H. Bell, Peter Maguire, Albert M. Xiao, Ru Hopkins, Tim B. Grant, Rebecca Bennett, Jean Wilson, James M. TI AAV9 Targets Cone Photoreceptors in the Nonhuman Primate Retina SO PLOS ONE LA English DT Article ID LEBERS CONGENITAL AMAUROSIS; GENE-TRANSFER; THERAPY; VECTOR; TRANSDUCTION; ROD; PIGMENTOSA; BINDING; ACHROMATOPSIA; DYSTROPHIES AB Transduction of retinal pigment epithelial cells with an adeno-associated viral vector (AAV) based on serotype 2 has partially corrected retinal blindness in Leber congenital amaurosis type 2. However, many applications of gene therapy for retinal blindness rely on the efficient transduction of rod and cone photoreceptor which is difficult to achieve with first generation vector technology. To address this translational need, we evaluated rod and cone photoreceptor targeting of 4 novel AAV capsids (AAV7, AAV9, rh. 64R1 and rh. 8R) versus AAV2 and AAV8 in a foveated retina. Eyes of 20 nonhuman primates were injected subretinally in the proximity of the fovea. While numerous vectors efficiently transduced rods, only AAV9 targeted cones both centrally and peripherally efficiently at low doses, likely due to the abundance of galactosylated glycans, the primary receptor for AAV9, on cone photoreceptors. We conclude AAV9 is an ideal candidate for strategies that require restoration of cone photoreceptor function. C1 [Vandenberghe, Luk H.; Bell, Peter; Xiao, Ru; Grant, Rebecca; Wilson, James M.] Univ Penn, Dept Pathol & Lab Med, Gene Therapy Program, Philadelphia, PA USA. [Maguire, Albert M.; Hopkins, Tim B.; Bennett, Jean] Univ Penn, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 USA. RP Vandenberghe, LH (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. EM luk_vandenberghe@meei.harvard.edu; wilsonjm@mail.med.upenn.edu RI Wilson, James/F-9220-2011 OI Wilson, James/0000-0002-9630-3131 FU GlaxoSmithKline [NIH P30 DK47757]; Foundation Fighting Blindness; CHOP-PENN Pediatric Center for Retinal Degenerations; University of Pennsylvania; Evanina Mackall Foundation Trust at Scheie Eye Institute; Kirby Foundation FX The authors would like to acknowledge the support of GlaxoSmithKline for a research grant and NIH P30 DK47757 (JMW). This work was also supported by the Foundation Fighting Blindness (LHV, JB), its CHOP-PENN Pediatric Center for Retinal Degenerations (JB), Transdisciplinary Award Program in Translational Medicine and Therapeutics (TAPITMAT) from the University of Pennsylvania (LHV, JB), Research to Prevent Blindness, the Paul and Evanina Mackall Foundation Trust at Scheie Eye Institute, and the F.M. Kirby Foundation (JB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 27 Z9 27 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 30 PY 2013 VL 8 IS 1 AR e53463 DI 10.1371/journal.pone.0053463 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 098QM UT WOS:000315563800022 PM 23382846 ER PT J AU Pedrelli, P Bentley, K Vitali, M Clain, AJ Nyer, M Fava, M Farabaugh, AH AF Pedrelli, Paola Bentley, Kate Vitali, Mario Clain, Alisabet J. Nyer, Maren Fava, Maurizio Farabaugh, Amy H. TI Compulsive use of alcohol among college students SO PSYCHIATRY RESEARCH LA English DT Article DE College students; Compulsive drinking; Risky behaviors; Alcohol; Drug use ID ABUSE SCREENING-TEST; IDENTIFICATION TEST AUDIT; BINGE-DRINKING; USE DISORDERS; PSYCHOMETRIC PROPERTIES; HEAVY DRINKING; MENTAL-HEALTH; YOUNG-ADULTS; POLYDRUG USE; DRUG-USE AB Among college students alcohol consumption is associated with other high-risk behaviors that can lead to short- and long-term negative health consequences. Identification of college students consuming alcohol who are at high risk for problems may have important public health implications. This study examines the ability of the CHQ compulsive use of alcohol item to detect high-risk behaviors relative to other screening measures and its association with different dimensions of compulsive drinking. Three hundred thirty-two college students completed measures on compulsive drinking and hazardous behaviors. Results showed that among male students the CHQ compulsive use of alcohol item was not sensitive to detect hazardous alcohol consumption but co-occurred with the use of illicit drugs. Among female students it was sensitive to detect heavy drinking but not alcohol or drug problems. Among college students compulsive use of alcohol corresponds to an urge to consume alcohol that may be associated with use of illicit drugs in male students, with heavy drinking in female students and with substance use problems. This study suggest that the CHQ compulsive use of alcohol item should not be used as a stand-alone screening for alcohol or drug problems but it could be considered a marker for at-risk behaviors. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Pedrelli, Paola; Vitali, Mario; Clain, Alisabet J.; Nyer, Maren; Fava, Maurizio; Farabaugh, Amy H.] Massachusetts Gen Hosp, Depress & Clin Res Program, Boston, MA 02114 USA. [Pedrelli, Paola; Fava, Maurizio; Farabaugh, Amy H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Bentley, Kate] Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02114 USA. RP Pedrelli, P (reprint author), Massachusetts Gen Hosp, Depress & Clin Res Program, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM ppedrelli@partners.org FU NIAAA NIH HHS [K23 AA020064] NR 56 TC 1 Z9 1 U1 1 U2 28 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD JAN 30 PY 2013 VL 205 IS 1-2 BP 95 EP 102 DI 10.1016/j.psychres.2012.08.012 PG 8 WC Psychiatry SC Psychiatry GA 094HB UT WOS:000315252500017 PM 22951374 ER PT J AU Das, B Kashino, SS Pulu, I Kalita, D Swami, V Yeger, H Felsher, DW Campos-Neto, A AF Das, Bikul Kashino, Suely S. Pulu, Ista Kalita, Deepjyoti Swami, Vijay Yeger, Herman Felsher, Dean W. Campos-Neto, Antonio TI CD271(+) Bone Marrow Mesenchymal Stem Cells May Provide a Niche for Dormant Mycobacterium tuberculosis SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID IN-VITRO; RECURRENT TUBERCULOSIS; PROGENITOR CELLS; GROWTH; VIVO; POPULATION; MODEL; MACROPHAGES; PERSISTENCE; INFECTION AB Mycobacterium tuberculosis (Mtb) can persist in hostile intracellular microenvironments evading immune cells and drug treatment. However, the protective cellular niches where Mtb persists remain unclear. We report that Mtb may maintain long-term intracellular viability in a human bone marrow (BM)-derived CD271(+)/CD45(-) mesenchymal stem cell (BM-MSC) population in vitro. We also report that Mtb resides in an equivalent population of BM-MSCs in a mouse model of dormant tuberculosis infection. Viable Mtb was detected in CD271(+)/CD45(-) BM-MSCs isolated from individuals who had successfully completed months of anti-Mtb drug treatment. These results suggest that CD271(+) BM-MSCs may provide a long-term protective intracellular niche in the host in which dormant Mtb can reside. C1 [Das, Bikul; Felsher, Dean W.] Stanford Univ, Sch Med, Dept Med, Div Oncol, Stanford, CA 94305 USA. [Das, Bikul; Felsher, Dean W.] Stanford Univ, Sch Med, Dept Pathol, Div Oncol, Stanford, CA 94305 USA. [Kashino, Suely S.; Campos-Neto, Antonio] Forsyth Inst, Global Infect Dis Res Ctr, Cambridge, MA 02142 USA. [Pulu, Ista; Swami, Vijay] RIWATCH, Roing 792110, Arunachal Prade, India. [Kalita, Deepjyoti] Indian Inst Technol, KaviKrishna Lab, Gauhati 781039, India. [Kalita, Deepjyoti] Gauhati Med Coll, Dept Microbiol, Gauhati 781032, India. [Yeger, Herman] Hosp Sick Children, Dept Pediat Lab Med, Toronto, ON M5G 1X8, Canada. RP Das, B (reprint author), Stanford Univ, Sch Med, Dept Med, Div Oncol, Stanford, CA 94305 USA. EM bikuldas@stanford.edu; dfelsher@stanford.edu FU Bill & Melinda Gates Foundation through the "Grand Challenges Exploration Initiative"; Canadian Cancer Society; KaviKrishna Foundation, Sualkuchi, Assam, India; Laurel Foundation; NIH [R01AI076425, R01 CA105102, CA89305-0351, CA112973]; Department of Defense [PR080163] FX The work was funded by a grant from the Bill & Melinda Gates Foundation through the "Grand Challenges Exploration Initiative" (B. D.). Additional funding was obtained from the Canadian Cancer Society (B. D.); the KaviKrishna Foundation, Sualkuchi, Assam, India (D. K. and I. P.); Laurel Foundation (B. D. and D. W. F.); NIH grants R01AI076425 (A.C.-N.), R01 CA105102, CA89305-0351, and CA112973; and Department of Defense grant PR080163 (D.W.F.). NR 63 TC 33 Z9 36 U1 0 U2 11 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD JAN 30 PY 2013 VL 5 IS 170 AR 170ra13 DI 10.1126/scitranslmed.3004912 PG 10 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 081SR UT WOS:000314343100003 PM 23363977 ER PT J AU Predina, J Eruslanov, E Judy, B Kapoor, V Cheng, GJ Wang, LC Sun, J Moon, EK Fridlender, ZG Albelda, S Singhal, S AF Predina, Jarrod Eruslanov, Evgeniy Judy, Brendan Kapoor, Veena Cheng, Guanjun Wang, Liang-Chuan Sun, Jing Moon, Edmund K. Fridlender, Zvi Gregorio Albelda, Steven Singhal, Sunil TI Changes in the local tumor microenvironment in recurrent cancers may explain the failure of vaccines after surgery SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material C1 [Predina, Jarrod; Eruslanov, Evgeniy; Judy, Brendan; Kapoor, Veena; Cheng, Guanjun; Singhal, Sunil] Univ Penn, Sch Med, Dept Surg, Thorac Surg Res Lab, Philadelphia, PA 19104 USA. [Wang, Liang-Chuan; Sun, Jing; Moon, Edmund K.; Fridlender, Zvi Gregorio; Albelda, Steven] Univ Penn, Sch Med, Dept Med, Div Pulm Allergy & Crit Care, Philadelphia, PA 19104 USA. [Singhal, Sunil] Philadelphia Vet Affairs Med Ctr, Surg Serv, Philadelphia, PA 19104 USA. RP Singhal, S (reprint author), Univ Penn, Sch Med, Dept Surg, Thorac Surg Res Lab, Philadelphia, PA 19104 USA. EM sunil.singhal@uphs.upenn.edu NR 0 TC 0 Z9 0 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 29 PY 2013 VL 110 IS 5 BP 1582 EP 1583 DI 10.1073/pnas.1211850110 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 084RZ UT WOS:000314558100011 ER PT J AU Predina, J Eruslanov, E Judy, B Kapoor, V Cheng, GJ Wang, LC Sun, J Moon, EK Fridlender, ZG Albelda, S Singhal, S AF Predina, Jarrod Eruslanov, Evgeniy Judy, Brendan Kapoor, Veena Cheng, Guanjun Wang, Liang-Chuan Sun, Jing Moon, Edmund K. Fridlender, Zvi Gregorio Albelda, Steven Singhal, Sunil TI Changes in the local tumor microenvironment in recurrent cancers may explain the failure of vaccines after surgery SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE immunology; tumor macrophages; T regulatory cells ID ADJUVANT IMMUNOTHERAPY; CELLS; CYTOREDUCTION; MACROPHAGES; INDUCTION; MECHANISM; CARCINOMA; RESECTION; ANTIGEN; GROWTH AB Each year, more than 700,000 people undergo cancer surgery in the United States. However, more than 40% of those patients develop recurrences and have a poor outcome. Traditionally, the medical community has assumed that recurrent tumors arise from selected tumor clones that are refractory to therapy. However, we found that tumor cells have few phenotypical differences after surgery. Thus, we propose an alternative explanation for the resistance of recurrent tumors. Surgery promotes inhibitory factors that allow lingering immunosuppressive cells to repopulate small pockets of residual disease quickly. Recurrent tumors and draining lymph nodes are infiltrated with M2 (CD11b(+)F4/80(hi)CD206(hi) and CD11b+F4/80(hi)CD124(hi)) macrophages and CD4(+)Foxp3(+) regulatory T cells. This complex network of immunosuppression in the surrounding tumor microenvironment explains the resistance of tumor recurrences to conventional cancer vaccines despite small tumor size, an intact antitumor immune response, and unaltered cancer cells. Therapeutic strategies coupling antitumor agents with inhibition of immunosuppressive cells potentially could impact the outcomes of more than 250,000 people each year. C1 [Predina, Jarrod; Eruslanov, Evgeniy; Judy, Brendan; Kapoor, Veena; Cheng, Guanjun; Singhal, Sunil] Univ Penn, Sch Med, Dept Surg, Thorac Surg Res Lab, Philadelphia, PA 19104 USA. [Wang, Liang-Chuan; Sun, Jing; Moon, Edmund K.; Fridlender, Zvi Gregorio; Albelda, Steven] Univ Penn, Sch Med, Dept Med, Div Pulm Allergy & Crit Care, Philadelphia, PA 19104 USA. [Singhal, Sunil] Philadelphia Vet Affairs Med Ctr, Surg Serv, Philadelphia, PA 19104 USA. RP Singhal, S (reprint author), Univ Penn, Sch Med, Dept Surg, Thorac Surg Res Lab, Philadelphia, PA 19104 USA. EM sunil.singhal@uphs.upenn.edu FU National Institutes of Health; Lavin Family Foundation; American Foundation for Cancer Research; National Lung Cancer Partnership FX We thank Theresa Busch and Cory Rice for their assistance in performing TGF-beta assays. S.S. is the recipient of a National Institutes of Health Paul Calabresi Scholarship. Further funding came from the Lavin Family Foundation (S.S.), the American Foundation for Cancer Research (S.S.), and the National Lung Cancer Partnership (S.S.). NR 32 TC 44 Z9 44 U1 1 U2 15 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 29 PY 2013 VL 110 IS 5 BP E415 EP E424 DI 10.1073/pnas.1211850110 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 130VG UT WOS:000317947600014 PM 23271806 ER PT J AU Solimini, NL Liang, AC Xu, CX Pavlova, NN Xu, QK Davoli, T Li, MZ Wong, KK Elledge, SJ AF Solimini, Nicole L. Liang, Anthony C. Xu, Chunxiao Pavlova, Natalya N. Xu, Qikai Davoli, Teresa Li, Mamie Z. Wong, Kwok-Kin Elledge, Stephen J. TI STOP gene Phactr4 is a tumor suppressor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROTEIN PHOSPHATASE-1; SOMATIC MUTATIONS; IN-VITRO; CANCER; RESOURCE; ACTIVATION; PRINCIPLES; ADDICTION; GENOMES; MOUSE AB Cancer develops through genetic and epigenetic alterations that allow unrestrained proliferation and increased survival. Using a genetic RNAi screen, we previously identified hundreds of suppressors of tumorigenesis and/or proliferation (STOP) genes that restrain normal cell proliferation. Our STOP gene set was significantly enriched for known and putative tumor suppressor genes. Here, we report a tumor-suppressive role for one STOP gene, phosphatase and actin regulator 4 (PHACTR4). Phactr4 is one of four members of the largely uncharacterized Phactr family of protein phosphatase 1 (PP1)and actin-binding proteins. Our work suggests that Phactr4 restrains normal cell proliferation and transformation. Depletion of Phactr4 with multiple shRNAs leads to increased proliferation and soft agar colony formation. Phactr4 acts, in part, through an Rb-dependent pathway, because Rb phosphorylation is maintained upon growth factor withdrawal in Phactr4-depleted cells. Examination of tumor copy number analysis and sequencing revealed that PHACTR4 is significantly deleted and mutant in many tumor subtypes. Furthermore, cancer cell lines with reduced Phactr4 expression exhibit tumor suppressor hypersensitivity upon Phactr4 complementation, leading to reduced proliferation, transformation, and tumor formation. Thus, Phactr4 acts as a tumor suppressor that is deleted and mutant in several cancers. C1 [Solimini, Nicole L.; Liang, Anthony C.; Pavlova, Natalya N.; Xu, Qikai; Davoli, Teresa; Li, Mamie Z.; Elledge, Stephen J.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Solimini, Nicole L.; Liang, Anthony C.; Pavlova, Natalya N.; Xu, Qikai; Davoli, Teresa; Li, Mamie Z.; Elledge, Stephen J.] Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Solimini, Nicole L.; Liang, Anthony C.; Pavlova, Natalya N.; Xu, Qikai; Davoli, Teresa; Li, Mamie Z.; Elledge, Stephen J.] Brigham & Womens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Xu, Chunxiao; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Wong, KK (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM kwong1@partners.org; selledge@genetics.med.harvard.edu OI wong, kwok kin/0000-0001-6323-235X FU Susan G. Komen for the Cure Foundation [KG080087]; Stand Up 2 Cancer; Department of Defense Breast Cancer Research Program FX We thank Simon Forbes and Andy Futreal for providing whole-genome sequencing data, Craig Mermel and Matthew Meyerson for providing cancer deletion data, Raju Kucherlapati for helpful discussions, and members of the Elledge laboratory for helpful discussions and critical reading of this manuscript. N.L.S. is supported by Susan G. Komen for the Cure Foundation Postdoctoral Fellowship KG080087. This work was supported by grants from Stand Up 2 Cancer and the Department of Defense Breast Cancer Research Program (to S.J.E.). S.J.E. is an investigator with the Howard Hughes Medical Institute. NR 32 TC 6 Z9 6 U1 0 U2 7 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 29 PY 2013 VL 110 IS 5 BP E407 EP E414 DI 10.1073/pnas.1221385110 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 130VG UT WOS:000317947600013 PM 23319639 ER PT J AU Budin, I Szostak, JW AF Budin, Itay Szostak, Jack W. TI Physical Models for Early Membrane Growth and Evolution SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 57th Annual Meeting of the Biophysical-Society CY FEB 02-06, 2013 CL Philadelphia, PA SP Biophys Soc C1 [Budin, Itay] Univ Calif Berkeley, Berkeley, CA USA. [Szostak, Jack W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 4 U2 18 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN 29 PY 2013 VL 104 IS 2 SU 1 BP 32A EP 32A PG 1 WC Biophysics SC Biophysics GA 105MI UT WOS:000316074300166 ER PT J AU Masia, R Yellen, G AF Masia, Ricard Yellen, Gary TI Native Currents in Hepatocytes with Characteristic Properties of Kir2 Channels SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 57th Annual Meeting of the Biophysical-Society CY FEB 02-06, 2013 CL Philadelphia, PA SP Biophys Soc C1 [Masia, Ricard] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yellen, Gary] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN 29 PY 2013 VL 104 IS 2 SU 1 BP 129A EP 129A PG 1 WC Biophysics SC Biophysics GA 105MI UT WOS:000316074301160 ER PT J AU Yang, DR Feldman, T Halvorsen, K Wong, W AF Yang, Darren Feldman, Ted Halvorsen, Ken Wong, Wesley TI Elucidating Hydrodynamic Force Regulation of Von Willebrand Factor in Hemostasis SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 57th Annual Meeting of the Biophysical-Society CY FEB 02-06, 2013 CL Philadelphia, PA SP Biophys Soc C1 [Yang, Darren; Feldman, Ted] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Halvorsen, Ken; Wong, Wesley] Harvard Univ, Sch Med, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN 29 PY 2013 VL 104 IS 2 SU 1 BP 168A EP 168A PG 1 WC Biophysics SC Biophysics GA 105MI UT WOS:000316074301355 ER PT J AU Song, LK Sun, ZYJ Kim, M Strong, RK Kwong, PD Wagner, G Reinherz, EL AF Song, Likai Sun, Zhen-Yu J. Kim, Mikyung Strong, Roland K. Kwong, Peter D. Wagner, Gerhard Reinherz, Ellis L. TI Interactions between Anti-HIV Antibodies and their Lipid-Embedded Epitopes Defined by EPR Spectroscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 57th Annual Meeting of the Biophysical-Society CY FEB 02-06, 2013 CL Philadelphia, PA SP Biophys Soc C1 [Song, Likai] Natl High Magnet Field Lab, Tallahassee, FL USA. [Sun, Zhen-Yu J.; Kim, Mikyung; Wagner, Gerhard; Reinherz, Ellis L.] Harvard Univ, Sch Med, Boston, MA USA. [Kim, Mikyung; Reinherz, Ellis L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Strong, Roland K.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Kwong, Peter D.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN 29 PY 2013 VL 104 IS 2 SU 1 BP 219A EP 219A PG 1 WC Biophysics SC Biophysics GA 105MI UT WOS:000316074302123 ER PT J AU Hochberg, LR AF Hochberg, Leigh R. TI Intracortical Brain-Computer Interfaces for the Restoration of Communication and Mobility SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 57th Annual Meeting of the Biophysical-Society CY FEB 02-06, 2013 CL Philadelphia, PA SP Biophys Soc C1 [Hochberg, Leigh R.] Providence VA Med Ctr, Ctr Neurorestorat & Neurotechnol, Providence, RI USA. [Hochberg, Leigh R.] Brown Univ, Sch Engn, Providence, RI 02912 USA. [Hochberg, Leigh R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hochberg, Leigh R.] Harvard Univ, Sch Med, Boston, MA USA. OI Hochberg, Leigh/0000-0003-0261-2273 NR 0 TC 0 Z9 0 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN 29 PY 2013 VL 104 IS 2 SU 1 BP 376A EP 376A PG 1 WC Biophysics SC Biophysics GA 105MI UT WOS:000316074303423 ER PT J AU Pineda, J Marineau, J Estiu, G Bradner, J AF Pineda, Javier Marineau, Jason Estiu, Guille Bradner, James TI Molecular Dynamics of DOT1L and Modeling of EZH2 SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 57th Annual Meeting of the Biophysical-Society CY FEB 02-06, 2013 CL Philadelphia, PA SP Biophys Soc C1 [Pineda, Javier; Estiu, Guille] Univ Notre Dame, Notre Dame, IN 46556 USA. [Marineau, Jason; Bradner, James] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN 29 PY 2013 VL 104 IS 2 SU 1 BP 403A EP 403A PG 1 WC Biophysics SC Biophysics GA 105MI UT WOS:000316074304052 ER PT J AU Jo, MH Peisley, A Lin, C Wu, B Orme-Johnson, M Walz, T Hohng, S Hur, S AF Jo, Myung Hyun Peisley, Alys Lin, Cecilie Wu, Bin Orme-Johnson, McGhee Walz, Thomas Hohng, Sungchul Hur, Sun TI Kinetic Mechanism for Viral DSRNA Length Discrimination by MDA5 Filaments SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 57th Annual Meeting of the Biophysical-Society CY FEB 02-06, 2013 CL Philadelphia, PA SP Biophys Soc C1 [Jo, Myung Hyun; Hohng, Sungchul] Seoul Natl Univ, Seoul, South Korea. [Peisley, Alys; Lin, Cecilie; Wu, Bin; Walz, Thomas; Hur, Sun] Harvard Univ, Sch Med, Boston, MA USA. [Orme-Johnson, McGhee] Childrens Hosp Boston, Program Cellular & Mol Med, Boston, MA USA. RI Wu, Bin/C-4715-2015 NR 0 TC 0 Z9 0 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN 29 PY 2013 VL 104 IS 2 SU 1 BP 420A EP 420A PG 1 WC Biophysics SC Biophysics GA 105MI UT WOS:000316074304141 ER PT J AU Feng, HJ Jounaidi, Y Forman, SA AF Feng, Hua-Jun Jounaidi, Youssef Forman, Stuart A. TI Modulation of Delta Subunit-Containing GABA(A) Receptors by Etomidate Depends on Subunit Arrangement SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 57th Annual Meeting of the Biophysical-Society CY FEB 02-06, 2013 CL Philadelphia, PA SP Biophys Soc C1 [Feng, Hua-Jun; Jounaidi, Youssef; Forman, Stuart A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN 29 PY 2013 VL 104 IS 2 SU 1 BP 637A EP 637A PG 1 WC Biophysics SC Biophysics GA 105MI UT WOS:000316074306219 ER PT J AU Jayakar, SS Zhou, XJ Dostalova, Z Dailey, WP Miller, KW Eckenhoff, RG Cohen, JB AF Jayakar, Selwyn S. Zhou, Xiaojuan Dostalova, Zuzana Dailey, William P. Miller, Keith W. Eckenhoff, Roderic G. Cohen, Jonathan B. TI Identifying the Propofol Binding Site(S) in Heterologously Expressed Human Alpha1 Beta3 Gaba-A Receptors using a Photoreactive Propofol Analog SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 57th Annual Meeting of the Biophysical-Society CY FEB 02-06, 2013 CL Philadelphia, PA SP Biophys Soc C1 [Jayakar, Selwyn S.; Cohen, Jonathan B.] Harvard Univ, Sch Med, Boston, MA USA. [Zhou, Xiaojuan; Dostalova, Zuzana; Miller, Keith W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dailey, William P.; Eckenhoff, Roderic G.] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN 29 PY 2013 VL 104 IS 2 SU 1 BP 637A EP 637A PG 1 WC Biophysics SC Biophysics GA 105MI UT WOS:000316074306218 ER PT J AU Stewart, D Hotta, M Forman, SA AF Stewart, Deirdre Hotta, Mayo Forman, Stuart A. TI State-Dependent Etomidate Binding in GABA(A) Receptors Probed with Cysteine Substitution and Protection from Modification SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 57th Annual Meeting of the Biophysical-Society CY FEB 02-06, 2013 CL Philadelphia, PA SP Biophys Soc C1 [Stewart, Deirdre; Hotta, Mayo; Forman, Stuart A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN 29 PY 2013 VL 104 IS 2 SU 1 BP 637A EP 637A PG 1 WC Biophysics SC Biophysics GA 105MI UT WOS:000316074306217 ER PT J AU Csordas, G Seifert, EL Golenar, T Moffat, C Perez, SD Weaver, D Bogorad, R Koteliansky, V Mootha, VK Hajnoczky, G AF Csordas, Gyoergy Seifert, Erin L. Golenar, Tuende Moffat, Cynthia Perez, Sergio de la Fuente Weaver, David Bogorad, Roman Koteliansky, Victor Mootha, Vamsi K. Hajnoczky, Gyoergy TI MICU1-dependent Threshold and Cooperativity of Mitochondrial Ca2+ Uptake in the Liver SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 57th Annual Meeting of the Biophysical-Society CY FEB 02-06, 2013 CL Philadelphia, PA SP Biophys Soc C1 [Csordas, Gyoergy; Seifert, Erin L.; Golenar, Tuende; Moffat, Cynthia; Perez, Sergio de la Fuente; Weaver, David; Hajnoczky, Gyoergy] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Bogorad, Roman; Koteliansky, Victor] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Mootha, Vamsi K.] Harvard Univ, Sch Med, Boston, MA USA. [Mootha, Vamsi K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Bogorad, Roman/G-2609-2011 NR 0 TC 0 Z9 0 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN 29 PY 2013 VL 104 IS 2 SU 1 BP 655A EP 655A PG 1 WC Biophysics SC Biophysics GA 105MI UT WOS:000316074306312 ER PT J AU Golenar, T Csordas, G Seifert, EL Moffat, C Perocchi, F Sancak, Y Weaver, D Mootha, VK Hajnoczky, G AF Golenar, Tuende Csordas, Gyoergy Seifert, Erin L. Moffat, Cynthia Perocchi, Fabiana Sancak, Yasemin Weaver, David Mootha, Vamsi K. Hajnoczky, Gyoergy TI Reprogramming of Mitochondrial Ca2+ Handling in MICU1-Deficient HeLa Cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 57th Annual Meeting of the Biophysical-Society CY FEB 02-06, 2013 CL Philadelphia, PA SP Biophys Soc C1 [Golenar, Tuende; Csordas, Gyoergy; Seifert, Erin L.; Moffat, Cynthia; Weaver, David; Hajnoczky, Gyoergy] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Perocchi, Fabiana; Sancak, Yasemin; Mootha, Vamsi K.] Harvard Univ, Sch Med, Boston, MA USA. [Perocchi, Fabiana; Sancak, Yasemin; Mootha, Vamsi K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN 29 PY 2013 VL 104 IS 2 SU 1 BP 655A EP 655A PG 1 WC Biophysics SC Biophysics GA 105MI UT WOS:000316074306311 ER PT J AU Chaudhuri, D Artiga, D Clapham, DE AF Chaudhuri, Dipayan Artiga, Daniel Clapham, David E. TI Properties of the Mitochondrial Permeability Transition in Drosophila S2R+Cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 57th Annual Meeting of the Biophysical-Society CY FEB 02-06, 2013 CL Philadelphia, PA SP Biophys Soc C1 [Chaudhuri, Dipayan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Artiga, Daniel] Harvard Univ, Boston, MA 02115 USA. [Clapham, David E.] Boston Childrens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN 29 PY 2013 VL 104 IS 2 SU 1 BP 658A EP 658A PG 1 WC Biophysics SC Biophysics GA 105MI UT WOS:000316074306326 ER PT J AU Castro, VM Clements, CC Murphy, SN Gainer, VS Fava, M Weilburg, JB Erb, JL Churchill, SE Kohane, IS Iosifescu, DV Smoller, JW Perlis, RH AF Castro, Victor M. Clements, Caitlin C. Murphy, Shawn N. Gainer, Vivian S. Fava, Maurizio Weilburg, Jeffrey B. Erb, Jane L. Churchill, Susanne E. Kohane, Isaac S. Iosifescu, Dan V. Smoller, Jordan W. Perlis, Roy H. TI QT interval and antidepressant use: a cross sectional study of electronic health records SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Article ID VENTRICULAR-ARRHYTHMIA; ANTIPSYCHOTIC-DRUGS; PROLONGATION; DEPRESSION; VALIDATION; ENTERPRISE; SERTRALINE; SAFETY; DEATH AB Objective To quantify the impact of citalopram and other selective serotonin reuptake inhibitors on corrected QT interval (QTc), a marker of risk for ventricular arrhythmia, in a large and diverse clinical population. Design A cross sectional study using electrocardiographic, prescribing, and clinical data from electronic health records to explore the relation between antidepressant dose and QTc. Methadone, an opioid known to prolong QT, was included to demonstrate assay sensitivity. Setting A large New England healthcare system comprising two academic medical centres and outpatient clinics. Participants 38 397 adult patients with an electrocardiogram recorded after prescription of antidepressant or methadone between February 1990 and August 2011. Main outcome measures Relation between antidepressant dose and QTc interval in linear regression, adjusting for potential clinical and demographic confounding variables. For a subset of patients, change in QTc after drug dose was also examined. Results Dose-response association with QTc prolongation was identified for citalopram (adjusted beta 0.10 (SE 0.04), P<0.01), escitalopram (adjusted beta 0.58 (0.15), P<0.001), and amitriptyline (adjusted beta 0.11 (0.03), P<0.001), but not for other antidepressants examined. An association with QTc shortening was identified for bupropion (adjusted beta 0.02 (0.01) P<0.05). Within-subject paired observations supported the QTc prolonging effect of citalopram (10 mg to 20 mg, mean QTc increase 7.8 (SE 3.6) ms, adjusted P<0.05; and 20 mg to 40 mg, mean QTc increase 10.3 (4.0) ms, adjusted P<0.01). Conclusions This study confirmed a modest prolongation of QT interval with citalopram, and identified additional antidepressants with similar observed risk. Pharmacovigilance studies using electronic health record data may be a useful method of identifying potential risk associated with treatments. C1 [Castro, Victor M.; Gainer, Vivian S.] Partners HealthCare Syst, Partners Res Comp, Constitut Ctr 1, Boston, MA 02129 USA. [Clements, Caitlin C.; Smoller, Jordan W.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Clements, Caitlin C.; Perlis, Roy H.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Expt Drugs & Diagnost, Boston, MA 02114 USA. [Murphy, Shawn N.] Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. [Murphy, Shawn N.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Fava, Maurizio; Weilburg, Jeffrey B.] Massachusetts Gen Hosp, Dept Psychiat, Depress Clin, Boston, MA 02114 USA. [Fava, Maurizio; Weilburg, Jeffrey B.] Massachusetts Gen Hosp, Dept Psychiat, Res Program, Boston, MA 02114 USA. [Erb, Jane L.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02215 USA. [Churchill, Susanne E.] Partners HealthCare Syst, Informat Syst, Natl Ctr Biomed Comp I2b2, Boston, MA 02215 USA. [Kohane, Isaac S.] Brigham & Womens Hosp, Dept Med, Natl Ctr Biomed Comp I2b2, Boston, MA 02215 USA. [Iosifescu, Dan V.] Mt Sinai Sch Med, Dept Psychiat, Mood & Anxiety Disorders Program, New York, NY 10029 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM rperlis@partners.org FU NIH/National Library of Medicine [2U54LM008748]; National Institute of Mental Health [R01MH086026]; Proteus Biomedical; Pamlab; Genomind; RIDventures; Concordant Rater Systems; Massachusetts General Hospital Psychiatry Academy; Abbott Laboratories; Affectis Pharmaceuticals AG; Alkermes; Amarin Pharma; Aspect Medical Systems; AstraZeneca; Auspex Pharmaceuticals; Bayer AG; Best Practice Project Management; BioMarin Pharmaceuticals; Biovail Corporation; BrainCells; Bristol-Myers Squibb; CeNeRx BioPharma; Cephalon; CNS Response; Compellis Pharmaceuticals; Cypress Pharmaceutical; DiagnoSearch Life Sciences; Dinippon Sumitomo Pharma; Dov Pharmaceuticals; Edgemont Pharmaceuticals; Eisai; Eli Lilly; EnVivo Pharmaceuticals; ePharmaSolutions; EPIX Pharmaceuticals; Euthymics Bioscience; Fabre-Kramer Pharmaceuticals; Forest Pharmaceuticals; GlaxoSmithKline; Grunenthal GmbH; i3 Innovus/Ingenis; Janssen Pharmaceutica; Jazz Pharmaceuticals; Johnson & Johnson Pharmaceutical Research Development; Knoll Pharmaceuticals; Labopharm; Lorex Pharmaceuticals; Lundbeck; MedAvante; Merck; MSI Methylation Sciences; Naurex; Neuralstem; Neuronetics; NextWave Pharmaceuticals; Novartis AG; Nutrition 21; Orexigen Therapeutics; Organon Pharmaceuticals; Otsuka Pharmaceuticals; Pfizer; PharmaStar; Pharmavite; PharmoRx Therapeutics; Precision Human Biolaboratory; Prexa Pharmaceuticals; Puretech Ventures; PsychoGenics; Psylin Neurosciences; Rexahn Pharmaceuticals; Ridge Diagnostics; Roche; Sanofi-Aventis US; Sepracor; Servier Laboratories; Schering-Plough; Solvay Pharmaceuticals; Somaxon Pharmaceuticals; Somerset Pharmaceuticals; Sunovion Pharmaceuticals; Supernus Pharmaceuticals; Synthelabo; Takeda Pharmaceutical; Tal Medical; Tetragenex Pharmaceuticals; TransForm Pharmaceuticals; Transcept Pharmaceuticals; Vanda Pharmaceuticals; Abbot Laboratories; BioResearch; Clintara; Covance; Covidien; ElMindA; Euthymics; Bioscience; Ganeden Biotech; Icon Clinical Research; i3 Innovus/Ingenix; Lichtwer Pharma GmbH; National Alliance for Research on Schizophrenia & Depression (NARSAD); National Center for Complementary and Alternative Medicine (NCCAM); National Institute of Drug Abuse (NIDA); National Institute of Mental Health (NIMH); Photothera; Roche Pharmaceuticals; RCT Logic; Sanofi-Aventis; Shire; Wyeth-Ayerst Laboratories FX The project was supported by the NIH/National Library of Medicine (award No 2U54LM008748 to ISK) and the National Institute of Mental Health (award No R01MH086026 to RHP). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Library of Medicine or the National Institutes of Health.; All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: RHP has received consulting fees from or served on scientific advisory boards for Proteus Biomedical, Pamlab, Genomind, and RIDventures, and has received research grant support from Proteus Biomedical and royalties from Concordant Rater Systems. JWS has served as a consultant for the Medical Letter. DVI has received payment for lectures including service on speakers' bureaus from the Massachusetts General Hospital Psychiatry Academy and has served as a consultant for CNS Response. MF has received consulting fees from or served on scientific advisor boards for Abbott Laboratories, Affectis Pharmaceuticals AG, Alkermes, Amarin Pharma, Aspect Medical Systems, AstraZeneca, Auspex Pharmaceuticals, Bayer AG, Best Practice Project Management, BioMarin Pharmaceuticals, Biovail Corporation, BrainCells, Bristol-Myers Squibb, CeNeRx BioPharma, Cephalon, CNS Response, Compellis Pharmaceuticals, Cypress Pharmaceutical, DiagnoSearch Life Sciences, Dinippon Sumitomo Pharma, Dov Pharmaceuticals, Edgemont Pharmaceuticals, Eisai, Eli Lilly, EnVivo Pharmaceuticals, ePharmaSolutions, EPIX Pharmaceuticals, Euthymics Bioscience, Fabre-Kramer Pharmaceuticals, Forest Pharmaceuticals, GenOmind, GlaxoSmithKline, Grunenthal GmbH, i3 Innovus/Ingenis, Janssen Pharmaceutica, Jazz Pharmaceuticals, Johnson & Johnson Pharmaceutical Research & Development, Knoll Pharmaceuticals, Labopharm, Lorex Pharmaceuticals, Lundbeck, MedAvante, Merck, MSI Methylation Sciences, Naurex, Neuralstem, Neuronetics, NextWave Pharmaceuticals, Novartis AG, Nutrition 21, Orexigen Therapeutics, Organon Pharmaceuticals, Otsuka Pharmaceuticals, Pamlab, Pfizer, PharmaStar, Pharmavite, PharmoRx Therapeutics, Precision Human Biolaboratory, Prexa Pharmaceuticals, Puretech Ventures, PsychoGenics, Psylin Neurosciences, Rexahn Pharmaceuticals, Ridge Diagnostics, Roche, Sanofi-Aventis US, Sepracor, Servier Laboratories, Schering-Plough, Solvay Pharmaceuticals, Somaxon Pharmaceuticals, Somerset Pharmaceuticals, Sunovion Pharmaceuticals, Supernus Pharmaceuticals, Synthelabo, Takeda Pharmaceutical, Tal Medical, Tetragenex Pharmaceuticals, TransForm Pharmaceuticals, Transcept Pharmaceuticals, Vanda Pharmaceuticals. MF has equity holdings in Compellis and has received research grant support from Abbot Laboratories, Alkermes, Aspect Medical Systems, AstraZeneca, BioResearch, BrainCells, Bristol-Myers Squibb, CeNeRx BioPharma, Cephalon, Clintara, Covance, Covidien, Eli Lilly, ElMindA, EnVivo Pharmaceuticals, Euthymics Bioscience, Forest Pharmaceuticals, Ganeden Biotech, GlaxoSmithKline, Icon Clinical Research, i3 Innovus/Ingenix, Johnson & Johnson Pharmaceutical Research & Development, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, National Alliance for Research on Schizophrenia & Depression (NARSAD), National Center for Complementary and Alternative Medicine (NCCAM), National Institute of Drug Abuse (NIDA), National Institute of Mental Health (NIMH), Novartis AG, Organon Pharmaceuticals, PamLab, Pfizer, Pharmavite, Photothera, Roche Pharmaceuticals, RCT Logic (formerly Clinical Trials Solutions), Sanofi-Aventis, Shire, Solvay Pharmaceuticals, Synthelabo, Wyeth-Ayerst Laboratories.; MF also holds a patent for Sequential Parallel Comparison Design (SPCD), which is licensed by MGH to RCT Logic, and copyright for the MGH Cognitive & Physical Functioning Questionnaire (CPFQ), Sexual Functioning Inventory (SFI), Antidepressant Treatment Response Questionnaire (ATRQ), Discontinuation-Emergent Signs & Symptoms (DESS), and SAFER; Lippincott, Williams & Wilkins; Wolkers Kluwer; World Scientific Publishing. NR 30 TC 61 Z9 64 U1 0 U2 14 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BMJ-BRIT MED J JI BMJ-British Medical Journal PD JAN 29 PY 2013 VL 346 AR f288 DI 10.1136/bmj.f288 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 084BH UT WOS:000314510400001 PM 23360890 ER PT J AU Vergani, A Tezza, S D'Addio, F Fotino, C Liu, KF Niewczas, M Bassi, R Molano, RD Kleffel, S Petrelli, A Soleti, A Ammirati, E Frigerio, M Visner, G Grassi, F Ferrero, ME Corradi, D Abdi, R Ricordi, C Sayegh, MH Pileggi, A Fiorina, P AF Vergani, Andrea Tezza, Sara D'Addio, Francesca Fotino, Carmen Liu, Kaifeng Niewczas, Monika Bassi, Roberto Molano, R. Damaris Kleffel, Sonja Petrelli, Alessandra Soleti, Antonio Ammirati, Enrico Frigerio, Maria Visner, Gary Grassi, Fabio Ferrero, Maria E. Corradi, Domenico Abdi, Reza Ricordi, Camillo Sayegh, Mohamed H. Pileggi, Antonello Fiorina, Paolo TI Long-Term Heart Transplant Survival by Targeting the Ionotropic Purinergic Receptor P2X7 SO CIRCULATION LA English DT Article DE immunology; P2X7R; rejection; transplantation ID T-CELL-ACTIVATION; ALLOGRAFT-REJECTION; ATP; TOLERANCE; DISEASE; DIFFERENTIATION; VASCULOPATHY; MAINTENANCE; EXPRESSION; INHIBITOR AB Background-Heart transplantation is a lifesaving procedure for patients with end-stage heart failure. Despite much effort and advances in the field, current immunosuppressive regimens are still associated with poor long-term cardiac allograft outcomes, and with the development of complications, including infections and malignancies, as well. The development of a novel, short-term, and effective immunomodulatory protocol will thus be an important achievement. The purine ATP, released during cell damage/activation, is sensed by the ionotropic purinergic receptor P2X7 (P2X7R) on lymphocytes and regulates T-cell activation. Novel clinical-grade P2X7R inhibitors are available, rendering the targeting of P2X7R a potential therapy in cardiac transplantation. Methods and Results-We analyzed P2X7R expression in patients and mice and P2X7R targeting in murine recipients in the context of cardiac transplantation. Our data demonstrate that P2X7R is specifically upregulated in graft-infiltrating lymphocytes in cardiac-transplanted humans and mice. Short-term P2X7R targeting with periodate-oxidized ATP promotes long-term cardiac transplant survival in 80% of murine recipients of a fully mismatched allograft. Long-term survival of cardiac transplants was associated with reduced T-cell activation, T-helper cell 1/T-helper cell 17 differentiation, and inhibition of STAT3 phosphorylation in T cells, thus leading to a reduced transplant infiltrate and coronaropathy. In vitro genetic upregulation of the P2X7R pathway was also shown to stimulate T-helper cell 1/T-helper cell 17 cell generation. Finally, P2X7R targeting halted the progression of coronaropathy in a murine model of chronic rejection as well. Conclusions-P2X7R targeting is a novel clinically relevant strategy to prolong cardiac transplant survival. (Circulation. 2013;127:463-475.) C1 [Fiorina, Paolo] Harvard Univ, TRC, Div Nephrol, Sch Med,Boston Childrens Hosp, Boston, MA 02115 USA. [Vergani, Andrea; Tezza, Sara; D'Addio, Francesca; Bassi, Roberto; Kleffel, Sonja; Abdi, Reza; Sayegh, Mohamed H.; Fiorina, Paolo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Vergani, Andrea; D'Addio, Francesca; Bassi, Roberto; Petrelli, Alessandra; Ammirati, Enrico; Fiorina, Paolo] Hosp San Raffaele, I-20132 Milan, Italy. [Fotino, Carmen; Molano, R. Damaris; Ricordi, Camillo; Pileggi, Antonello] Univ Miami, Diabet Res Inst, Miami, FL USA. [Niewczas, Monika] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. [Soleti, Antonio] Medestea, Turin, Italy. [Ammirati, Enrico; Frigerio, Maria] Osped Niguarda Ca Granda, Cardiothorac & Vasc Dept, Milan, Italy. [Grassi, Fabio] Biomed Res Inst, Bellinzona, Switzerland. [Ferrero, Maria E.] Univ Milan, Milan, Italy. [Corradi, Domenico] Univ Parma, I-43100 Parma, Italy. RP Fiorina, P (reprint author), Harvard Univ, TRC, Div Nephrol, Sch Med,Boston Childrens Hosp, Enders Bldg,5th Floor,Rm EN530,300 Longwood Ave, Boston, MA 02115 USA. EM paolo.fiorina@childrens.harvard.edu RI Molano, Ruth Damaris/B-8633-2015; Petrelli, Alessandra/M-7004-2015; Corradi, Domenico/O-1666-2015; Pileggi, Antonello/A-2394-2008; D'Addio, Francesca/F-3417-2017; OI Molano, Ruth Damaris/0000-0002-6132-8750; Petrelli, Alessandra/0000-0002-5639-9415; Corradi, Domenico/0000-0002-8836-4778; Pileggi, Antonello/0000-0001-7819-2813; D'Addio, Francesca/0000-0002-0345-0694; Fotino, Carmen/0000-0002-2645-6546; Ricordi, Camillo/0000-0001-8092-7153 FU JDRF; ASN; ADA; Boston Children's Hospital; Minister of Health of Italy ["Staminali"RF-FSR-2008-1213704]; NIH [T32DK007726-28] FX Dr Fiorina is the recipient of a JDRF-Career Development Award, an ASN Career Development Award, and an ADA mentor-based fellowship. He is supported by a Translational Research Program (TRP) grant from Boston Children's Hospital. Drs Fiorina and Vergani are recipients of a Minister of Health of Italy grant ("Staminali"RF-FSR-2008-1213704). Dr Vergani is supported by a NIH-Research Training Grant to Boston Children's Hospital in Pediatric Nephrology (T32DK007726-28). Dr Bassi is supported by an ADA mentor-based fellowship to Dr Fiorina. NR 43 TC 38 Z9 38 U1 0 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 29 PY 2013 VL 127 IS 4 BP 463 EP + DI 10.1161/CIRCULATIONAHA.112.123653 PG 18 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 079IK UT WOS:000314163600019 PM 23250993 ER PT J AU Januzzi, JL Troughton, R AF Januzzi, James L., Jr. Troughton, Richard TI Are Serial BNP Measurements Useful in Heart Failure Management? Serial Natriuretic Peptide Measurements Are Useful in Heart Failure Management SO CIRCULATION LA English DT Editorial Material ID VENTRICULAR SYSTOLIC DYSFUNCTION; PROBNP-GUIDED MANAGEMENT; PROGNOSTIC VALUE; THERAPY; IMPROVE; CARE; ASSOCIATION; MORTALITY; TRIAL; MORBIDITY C1 [Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Troughton, Richard] Univ Otago, Christchurch Heart Inst, Christchurch, New Zealand. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, 32 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM JJanuzzi@partners.org NR 28 TC 55 Z9 61 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 29 PY 2013 VL 127 IS 4 BP 500 EP 507 DI 10.1161/CIRCULATIONAHA.112.120485 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 079IK UT WOS:000314163600022 PM 23357662 ER PT J AU Fusaro, VA Patil, P Chi, CL Contant, CF Tonellato, PJ AF Fusaro, Vincent A. Patil, Prasad Chi, Chih-Lin Contant, Charles F. Tonellato, Peter J. TI A Systems Approach to Designing Effective Clinical Trials Using Simulations SO CIRCULATION LA English DT Article DE bioinformatics; clinical trials; individualized medicine; modeling; pharmacogenetics; simulations; warfarin ID NONVALVULAR ATRIAL-FIBRILLATION; WARFARIN DOSE REQUIREMENTS; DOSING ALGORITHM; PHARMACOGENETIC DATA; CHINESE PATIENTS; CYP2C9; VKORC1; MAINTENANCE; MODEL; ANTICOAGULATION AB Background-Pharmacogenetics in warfarin clinical trials have failed to show a significant benefit in comparison with standard clinical therapy. This study demonstrates a computational framework to systematically evaluate preclinical trial design of target population, pharmacogenetic algorithms, and dosing protocols to optimize primary outcomes. Methods and Results-We programmatically created an end-to-end framework that systematically evaluates warfarin clinical trial designs. The framework includes options to create a patient population, multiple dosing strategies including genetic-based and nongenetic clinical-based, multiple-dose adjustment protocols, pharmacokinetic/pharmacodynamics modeling and international normalization ratio prediction, and various types of outcome measures. We validated the framework by conducting 1000 simulations of the Applying Pharmacogenetic Algorithms to Individualize Dosing of Warfarin (CoumaGen) clinical trial primary end points. The simulation predicted a mean time in therapeutic range of 70.6% and 72.2% (P=0.47) in the standard and pharmacogenetic arms, respectively. Then, we evaluated another dosing protocol under the same original conditions and found a significant difference in the time in therapeutic range between the pharmacogenetic and standard arm (78.8% versus 73.8%; P=0.0065), respectively. Conclusions-We demonstrate that this simulation framework is useful in the preclinical assessment phase to study and evaluate design options and provide evidence to optimize the clinical trial for patient efficacy and reduced risk. (Circulation. 2013;127:517-526.) C1 [Fusaro, Vincent A.; Chi, Chih-Lin; Tonellato, Peter J.] Harvard Univ, Ctr Biomed Informat, Sch Med, Boston, MA 02115 USA. [Patil, Prasad] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. [Contant, Charles F.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. RP Tonellato, PJ (reprint author), Harvard Univ, Ctr Biomed Informat, Sch Med, 10 Shattuck St, Boston, MA 02115 USA. EM peter_tonellato@hms.harvard.edu FU National Library of Medicine [R01LM010130, K99LM011020, T15LM007092] FX This research was supported by grants from the National Library of Medicine R01LM010130 (to Dr Tonellato) and K99LM011020 and T15LM007092 (to Dr Fusaro). NR 34 TC 4 Z9 5 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JAN 29 PY 2013 VL 127 IS 4 BP 517 EP + DI 10.1161/CIRCULATIONAHA.112.123034 PG 16 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 079IK UT WOS:000314163600026 PM 23261867 ER PT J AU Beck, D Niessner, H Smalley, KSM Flaherty, K Paraiso, KHT Busch, C Sinnberg, T Vasseur, S Iovanna, JL Driessen, S Stork, B Wesselborg, S Schaller, M Biedermann, T Bauer, J Lasithiotakis, K Weide, B Eberle, J Schittek, B Schadendorf, D Garbe, C Kulms, D Meier, F AF Beck, Daniela Niessner, Heike Smalley, Keiran S. M. Flaherty, Keith Paraiso, Kim H. T. Busch, Christian Sinnberg, Tobias Vasseur, Sophie Iovanna, Juan Lucio Driessen, Stefan Stork, Bjoern Wesselborg, Sebastian Schaller, Martin Biedermann, Tilo Bauer, Juergen Lasithiotakis, Konstantinos Weide, Benjamin Eberle, Juergen Schittek, Birgit Schadendorf, Dirk Garbe, Claus Kulms, Dagmar Meier, Friedegund TI Vemurafenib Potently Induces Endoplasmic Reticulum Stress-Mediated Apoptosis in BRAFV600E Melanoma Cells SO SCIENCE SIGNALING LA English DT Article ID UNFOLDED PROTEIN RESPONSE; RAF INHIBITOR RESISTANCE; ER STRESS; ACQUIRE RESISTANCE; TUMOR-CELLS; BRAF; DEATH; GROWTH; SURVIVAL; CANCER AB The V600E mutation in the kinase BRAF is frequently detected in melanomas and results in constitutive activation of BRAF, which then promotes cell proliferation by the mitogen-activated protein kinase signaling pathway. Although the BRAFV600E kinase inhibitor vemurafenib has remarkable antitumor activity in patients with BRAFV600E-mutated melanoma, its effects are limited by the onset of drug resistance. We found that exposure of melanoma cell lines with the BRAFV600E mutation to vemurafenib decreased the abundance of antiapoptotic proteins and induced intrinsic mitochondrial apoptosis. Vemurafenib-treated melanoma cells showed increased cytosolic concentration of calcium, a potential trigger for endoplasmic reticulum (ER) stress, which can lead to apoptosis. Consistent with an ER stress-induced response, vemurafenib decreased the abundance of the ER chaperone protein glucose-regulated protein 78, increased the abundance of the spliced isoform of the transcription factor X-box binding protein 1 (XBP1) (which transcriptionally activates genes involved in ER stress responses), increased the phosphorylation of the translation initiation factor eIF2 alpha (which would be expected to inhibit protein synthesis), and induced the expression of ER stress-related genes. Knockdown of the ER stress response protein activating transcription factor 4 (ATF4) significantly reduced vemurafenib-induced apoptosis. Moreover, the ER stress inducer thapsigargin prevented invasive growth of tumors formed from vemurafenib-sensitive melanoma cells in vivo. In melanoma cells with low sensitivity or resistance to vemurafenib, combination treatment with thapsigargin augmented or induced apoptosis. Thus, thapsigargin or other inducers of ER stress may be useful in combination therapies to overcome vemurafenib resistance. C1 [Beck, Daniela; Niessner, Heike; Busch, Christian; Sinnberg, Tobias; Schaller, Martin; Biedermann, Tilo; Bauer, Juergen; Lasithiotakis, Konstantinos; Weide, Benjamin; Schittek, Birgit; Garbe, Claus; Meier, Friedegund] Univ Tubingen, Dept Dermatol, Div Dermatol Oncol, D-72076 Tubingen, Germany. [Smalley, Keiran S. M.; Paraiso, Kim H. T.] H Lee Moffitt Canc Ctr & Res Inst, Dept Mol Oncol, Tampa, FL 33612 USA. [Smalley, Keiran S. M.; Paraiso, Kim H. T.] H Lee Moffitt Canc Ctr & Res Inst, Dept Cutaneous Oncol, Tampa, FL 33612 USA. [Flaherty, Keith] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Vasseur, Sophie; Iovanna, Juan Lucio] Ctr Rech INSERM, F-13288 Marseille, France. [Vasseur, Sophie] Inst J Paoli I Calmettes, F-13288 Marseille, France. [Vasseur, Sophie] Aix Marseille Univ, F-13288 Marseille, France. [Vasseur, Sophie] CRCM, CNRS, UMR7258, F-13288 Marseille, France. [Driessen, Stefan; Stork, Bjoern; Wesselborg, Sebastian] Univ Hosp Dusseldorf, Inst Mol Med, D-40225 Dusseldorf, Germany. [Eberle, Juergen] Charite Univ Med Berlin, Skin Canc Ctr Charite, Dept Dermatol & Allergy, D-10117 Berlin, Germany. [Schadendorf, Dirk] Univ Essen Gesamthsch, Dept Dermatol, D-45122 Essen, Germany. [Kulms, Dagmar] Univ Stuttgart, Inst Cell Biol & Immunol, D-70569 Stuttgart, Germany. [Kulms, Dagmar] Tech Univ Dresden, Dept Dermatol, D-01307 Dresden, Germany. RP Meier, F (reprint author), Univ Tubingen, Dept Dermatol, Div Dermatol Oncol, D-72076 Tubingen, Germany. EM friedegund.meier@t-online.de RI Kulms, Dagmar/H-1653-2014; Weide, Benjamin/N-3698-2013; Stork, Bjorn/C-2160-2011; Bauer, Jurgen/B-4656-2008 OI Stork, Bjorn/0000-0002-4167-7806; Bauer, Jurgen/0000-0001-8789-1536 FU Deutsche Forschungsgemeinschaft [SFB 773, SFB 685, SPP1394, BI 696/10-1]; University of Tuebingen, IZKF-Tuebingen; NIH [R01 CA161107-02]; Joanna M. Nicolay Foundation FX D.B., H.N., S. D., B. Stork, S. W., M. S., C. B., B. Schittek, C. G., and F. M. were supported by the Deutsche Forschungsgemeinschaft (SFB 773). T. B. was supported by the Deutsche Forschungsgemeinschaft (SFB 685, SPP1394, BI 696/10-1) and the University of Tuebingen, IZKF-Tuebingen, collaborative research program. K. S. M. S. was supported by NIH grant R01 CA161107-02. K. H. T. P. was supported by the Joanna M. Nicolay Foundation. NR 47 TC 38 Z9 40 U1 0 U2 8 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD JAN 29 PY 2013 VL 6 IS 260 AR ra7 DI 10.1126/scisignal.2003057 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 080CJ UT WOS:000314218500003 PM 23362240 ER PT J AU Gheorghiade, M Vaduganathan, M Fonarow, GC Bonow, RO AF Gheorghiade, Mihai Vaduganathan, Muthiah Fonarow, Gregg C. Bonow, Robert O. TI Rehospitalization for Heart Failure Problems and Perspectives SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review DE heart failure; outcomes; readmission ID VENTRICULAR EJECTION FRACTION; INITIATE LIFESAVING TREATMENT; OPTIMIZE-HF REGISTRY; BETA-BLOCKER THERAPY; CLINICAL-OUTCOMES; FOLLOW-UP; MEDICARE BENEFICIARIES; READMISSION RATES; EVEREST TRIAL; VASOPRESSIN ANTAGONISM AB With a prevalence of 5.8 million in the United States alone, heart failure (HF) is associated with high morbidity, mortality, and healthcare expenditures. Close to 1 million hospitalizations for heart failure (HHF) occur annually, accounting for over 6.5 million hospital days and a substantial portion of the estimated $37.2 billion that is spent each year on HF in the United States. Although some progress has been made in reducing mortality in patients hospitalized with HF, rates of rehospitalization continue to rise, and approach 30% within 60 to 90 days of discharge. Approximately half of HHF patients have preserved or relatively preserved ejection fraction (EF). Their post-discharge event rate is similar to those with reduced EF. HF readmission is increasingly being used as a quality metric, a basis for hospital reimbursement, and an outcome measure in HF clinical trials. In order to effectively prevent HF readmissions and improve overall outcomes, it is important to have a complete and longitudinal characterization of HHF patients. This paper highlights management strategies that when properly implemented may help reduce HF rehospitalizations and include adopting a mechanistic approach to cardiac abnormalities, treating noncardiac comorbidities, increasing utilization of evidence-based therapies, and improving care transitions, monitoring, and disease management. (J Am Coll Cardiol 2013;61:391-403) (C) 2013 by the American College of Cardiology Foundation C1 [Gheorghiade, Mihai; Bonow, Robert O.] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Chicago, IL 60611 USA. [Vaduganathan, Muthiah] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA. RP Gheorghiade, M (reprint author), Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, 645 N Michigan Ave,Suite 1006, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu RI Vila, Vanessa/B-4982-2014 FU Agency for Healthcare Research and Quality FX Dr. Gheorghiade is a consultant for Abbott Laboratories (modest), Astellas (modest), AstraZeneca (modest), Bayer Schering Pharma AG (significant), CorThera, Inc. (modest), Cytokinetics, Inc. (modest), DebioPharm SA (significant), Errekappa Terapeutici (Milan, Italy) (modest), GlaxoSmithKline (modest), Johnson & Johnson (modest), Medtronic (significant), Merck (modest), Novartis Pharma AG (significant), Otsuka Pharmaceuticals (significant), Pericor Therapeutics (significant), Protein Design Laboratories (modest), Sanofi-Aventis (modest), Sigma Tau (significant), and Solvay Pharmaceuticals (significant). Dr. Fonarow has received research support from the Agency for Healthcare Research and Quality (significant); and is a consultant for Medtronic (modest) and Novartis (significant). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 77 TC 144 Z9 148 U1 4 U2 33 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 29 PY 2013 VL 61 IS 4 BP 391 EP 403 DI 10.1016/j.jacc.2012.09.038 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 074TB UT WOS:000313835300003 PM 23219302 ER PT J AU Singer, DE AF Singer, Daniel E. TI Methodologic Problems in the Assessment of Bleed Scores SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Letter ID ATRIAL-FIBRILLATION; RISK; ANTICOAGULATION; HEMORRHAGE C1 Massachusetts Gen Hosp, Clin Epidemiol Unit, Boston, MA 02114 USA. RP Singer, DE (reprint author), Massachusetts Gen Hosp, Clin Epidemiol Unit, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM dsinger@partners.org NR 5 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 29 PY 2013 VL 61 IS 4 BP 481 EP 481 DI 10.1016/j.jacc.2012.09.052 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 074TB UT WOS:000313835300018 PM 23347783 ER PT J AU Lin, CT McKenzie, M Pell, J Caplan, L AF Lin, Chen-Tan McKenzie, Marlene Pell, Jonathan Caplan, Liron TI Health Care Provider Satisfaction With a New Electronic Progress Note Format: SOAP vs APSO Format SO JAMA INTERNAL MEDICINE LA English DT Letter ID INFORMATION C1 [Lin, Chen-Tan; McKenzie, Marlene; Pell, Jonathan] Univ Colorado, Sch Med, Dept Med, Div Gen Internal Med, Aurora, CO 80045 USA. [Caplan, Liron] Univ Colorado, Sch Med, Dept Med, Div Rheumatol, Aurora, CO 80045 USA. [Caplan, Liron] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Lin, CT (reprint author), Univ Colorado, Sch Med, Dept Med, Div Gen Internal Med, 12631 E 17th Ave,Box B-180,Acad Off Bldg 1,Room 8, Aurora, CO 80045 USA. EM ct.lin@ucdenver.edu NR 8 TC 5 Z9 5 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JAN 28 PY 2013 VL 173 IS 2 BP 160 EP 162 DI 10.1001/2013.jamainternmed.474 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 121JO UT WOS:000317239700019 PM 23403939 ER PT J AU Venkatesh, A Kline, JA Kabrhel, C AF Venkatesh, Arjun Kline, Jeffrey A. Kabrhel, Christopher TI Computed Tomography in the Emergency Department Setting Reply SO JAMA INTERNAL MEDICINE LA English DT Letter ID PULMONARY-EMBOLISM C1 [Venkatesh, Arjun] Yale Univ, Dept Emergency Med, New Haven, CT 06520 USA. [Kline, Jeffrey A.] Indiana Univ, Dept Emergency Med, Indianapolis, IN 46204 USA. [Kabrhel, Christopher] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Kabrhel, C (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 0 Emerson Pl,Ste 3B, Boston, MA 02114 USA. EM ckabrhel@partners.org NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JAN 28 PY 2013 VL 173 IS 2 BP 168 EP 168 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 121JO UT WOS:000317239700027 PM 23358841 ER PT J AU Beatty, AL Schiller, NB Whooley, MA AF Beatty, Alexis L. Schiller, Nelson B. Whooley, Mary A. TI Moderate Exercise for Improvement in 6-Minute Walk Test Performance in Stable Coronary Heart Disease Reply SO JAMA INTERNAL MEDICINE LA English DT Letter ID CARDIAC REHABILITATION PROGRAM C1 [Beatty, Alexis L.; Schiller, Nelson B.; Whooley, Mary A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Whooley, Mary A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Whooley, Mary A.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Beatty, AL (reprint author), Univ Calif San Francisco, Dept Med, 505 Parnassus Ave,Box 0124, San Francisco, CA 94143 USA. EM alexis.beatty@ucsf.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JAN 28 PY 2013 VL 173 IS 2 BP 169 EP 169 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 121JO UT WOS:000317239700029 PM 23358843 ER PT J AU Buys, AV Van Rooy, MJ Soma, P Van Papendorp, D Lipinski, B Pretorius, E AF Buys, Antoinette V. Van Rooy, Mia-Jean Soma, Prashilla Van Papendorp, Dirk Lipinski, Boguslaw Pretorius, Etheresia TI Changes in red blood cell membrane structure in type 2 diabetes: a scanning electron and atomic force microscopy study SO CARDIOVASCULAR DIABETOLOGY LA English DT Article DE Red blood cells; Atomic force microscopy; Scanning electron microscopy; Type 2 diabetes ID ERYTHROCYTE DEFORMABILITY; MELLITUS; ROUGHNESS; PLATELET; RBCS AB Red blood cells (RBCs) are highly deformable and possess a robust membrane that can withstand shear force. Previous research showed that in diabetic patients, there is a changed RBC ultrastructure, where these cells are elongated and twist around spontaneously formed fibrin fibers. These changes may impact erythrocyte function. Ultrastructural analysis of RBCs in inflammatory and degenerative diseases can no longer be ignored and should form a fundamental research tool in clinical studies. Consequently, we investigated the membrane roughness and ultrastructural changes in type 2 diabetes. Atomic force microscopy (AFM) was used to study membrane roughness and we correlate this with scanning electron microscopy (SEM) to compare results of both the techniques with the RBCs of healthy individuals. We show that the combined AFM and SEM analyses of RBCs give valuable information about the disease status of patients with diabetes. Effectiveness of treatment regimes on the integrity, cell shape and roughness of RBCs may be tracked, as this cell's health status is crucial to the overall wellness of the diabetic patient. C1 [Buys, Antoinette V.] Univ Pretoria, Unit Microscopy & Microanal, ZA-0007 Pretoria, South Africa. [Van Rooy, Mia-Jean; Soma, Prashilla; Van Papendorp, Dirk; Pretorius, Etheresia] Univ Pretoria, ARCADIA, Fac Hlth Sci, Dept Physiol, ZA-0007 Pretoria, South Africa. [Lipinski, Boguslaw] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Pretorius, E (reprint author), Univ Pretoria, ARCADIA, Fac Hlth Sci, Dept Physiol, ZA-0007 Pretoria, South Africa. EM resia.pretorius@up.ac.za OI Pretorius, Etheresia/0000-0002-9108-2384 NR 16 TC 43 Z9 45 U1 5 U2 44 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2840 J9 CARDIOVASC DIABETOL JI Cardiovasc. Diabetol. PD JAN 28 PY 2013 VL 12 AR 25 DI 10.1186/1475-2840-12-25 PG 6 WC Cardiac & Cardiovascular Systems; Endocrinology & Metabolism SC Cardiovascular System & Cardiology; Endocrinology & Metabolism GA 108FZ UT WOS:000316278500001 PM 23356738 ER PT J AU Drain, PK Losina, E Parker, G Giddy, J Ross, D Katz, JN Coleman, SM Bogart, LM Freedberg, KA Walensky, RP Bassett, IV AF Drain, Paul K. Losina, Elena Parker, Gary Giddy, Janet Ross, Douglas Katz, Jeffrey N. Coleman, Sharon M. Bogart, Laura M. Freedberg, Kenneth A. Walensky, Rochelle P. Bassett, Ingrid V. TI Risk Factors for Late-Stage HIV Disease Presentation at Initial HIV Diagnosis in Durban, South Africa SO PLOS ONE LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; SUB-SAHARAN AFRICA; MEDICAL-CARE; COLLABORATIVE ANALYSIS; FOOD INSECURITY; INFECTION; MORTALITY; HIV/AIDS; COHORT; ADULTS AB Background: After observing persistently low CD4 counts at initial HIV diagnosis in South Africa, we sought to determine risk factors for late-stage HIV disease presentation among adults. Methods: We surveyed adults prior to HIV testing at four outpatient clinics in Durban from August 2010 to November 2011. All HIV-infected adults were offered CD4 testing, and late-stage HIV disease was defined as a CD4 count<100 cells/mm(3). We used multivariate regression models to determine the effects of sex, emotional health, social support, distance from clinic, employment, perceived barriers to receiving healthcare, and foregoing healthcare to use money for food, clothing, or housing ("competing needs to healthcare'') on presentation with late-stage HIV disease. Results: Among 3,669 adults screened, 830 were enrolled, newly-diagnosed with HIV and obtained a CD4 result. Among those, 279 (33.6%) presented with late-stage HIV disease. In multivariate analyses, participants who lived >= 5 kilometers from the test site [adjusted odds ratio (AOR) 2.8, 95% CI 1.7-4.7], reported competing needs to healthcare (AOR 1.7, 95% CI 1.2-2.4), were male (AOR 1.7, 95% CI 1.2-2.3), worked outside the home (AOR 1.5, 95% CI 1.1-2.1), perceived health service delivery barriers (AOR 1.5, 95% CI 1.1-2.1), and/or had poor emotional health (AOR 1.4, 95% CI 1.0-1.9) had higher odds of late-stage HIV disease presentation. Conclusions: Independent risk factors for late-stage HIV disease presentation were from diverse domains, including geographic, economic, demographic, social, and psychosocial. These findings can inform various interventions, such as mobile testing or financial assistance, to reduce the risk of presentation with late-stage HIV disease. C1 [Drain, Paul K.; Freedberg, Kenneth A.; Walensky, Rochelle P.; Bassett, Ingrid V.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Losina, Elena; Freedberg, Kenneth A.; Walensky, Rochelle P.; Bassett, Ingrid V.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Drain, Paul K.; Losina, Elena; Freedberg, Kenneth A.; Walensky, Rochelle P.; Bassett, Ingrid V.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Drain, Paul K.; Losina, Elena; Walensky, Rochelle P.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Katz, Jeffrey N.] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Losina, Elena; Katz, Jeffrey N.] Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02115 USA. [Freedberg, Kenneth A.; Walensky, Rochelle P.; Bassett, Ingrid V.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. [Bogart, Laura M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Katz, Jeffrey N.; Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Katz, Jeffrey N.; Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Coleman, Sharon M.; Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Coleman, Sharon M.] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA USA. [Bogart, Laura M.] Boston Childrens Hosp, Boston, MA USA. [Parker, Gary; Giddy, Janet] McCord Hosp, Dept Med, Durban, South Africa. [Ross, Douglas] St Marys Hosp, Dept Med, Durban, South Africa. RP Drain, PK (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM pdrain@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X; Drain, Paul/0000-0003-3300-3817 FU Harvard Institute for Global Health; Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University [R24 TW007988]; National Institute of Mental Health [R01 MH090326, R01 MH073445]; National Institute of Allergy and Infectious Disease [K24 AI062476]; Harvard University Center for AIDS Research [P30 AI060354]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [K24 AR057827]; National Center for Research Resources [UL1 RR 025758]; Burke Global Health Fellowship; Claflin Distinguished Scholar Award FX This research was supported by the Harvard Institute for Global Health (PKD); the Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University R24 TW007988 (PKD); the National Institute of Mental Health R01 MH090326 (IVB) and R01 MH073445 (RPW); the National Institute of Allergy and Infectious Disease K24 AI062476 (KAF); the Harvard University Center for AIDS Research P30 AI060354; the National Institute of Arthritis and Musculoskeletal and Skin Diseases K24 AR057827 (EL); the National Center for Research Resources (the Harvard Catalyst UL1 RR 025758); the Burke Global Health Fellowship (IVB); and the Claflin Distinguished Scholar Award (IVB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 49 TC 15 Z9 17 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 28 PY 2013 VL 8 IS 1 AR e55305 DI 10.1371/journal.pone.0055305 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 093SF UT WOS:000315211500074 PM 23383147 ER PT J AU Robinson, CP Schwarz, EM Sternberg, PW AF Robinson, Carmie Puckett Schwarz, Erich M. Sternberg, Paul W. TI Identification of DVA Interneuron Regulatory Sequences in Caenorhabditis elegans SO PLOS ONE LA English DT Article ID C-ELEGANS; NERVOUS-SYSTEM; TRANSCRIPTION FACTORS; GENE-EXPRESSION; DNA-SEQUENCE; NEURON; DIFFERENTIATION; CELL; SPECIFICATION; CONSERVATION AB Background: The identity of each neuron is determined by the expression of a distinct group of genes comprising its terminal gene battery. The regulatory sequences that control the expression of such terminal gene batteries in individual neurons is largely unknown. The existence of a complete genome sequence for C. elegans and draft genomes of other nematodes let us use comparative genomics to identify regulatory sequences directing expression in the DVA interneuron. Methodology/Principal Findings: Using phylogenetic comparisons of multiple Caenorhabditis species, we identified conserved non-coding sequences in 3 of 10 genes (fax-1, nmr-1, and twk-16) that direct expression of reporter transgenes in DVA and other neurons. The conserved region and flanking sequences in an 85-bp intronic region of the twk-16 gene directs highly restricted expression in DVA. Mutagenesis of this 85 bp region shows that it has at least four regions. The central 53 bp region contains a 29 bp region that represses expression and a 24 bp region that drives broad neuronal expression. Two short flanking regions restrict expression of the twk-16 gene to DVA. A shared GA-rich motif was identified in three of these genes but had opposite effects on expression when mutated in the nmr-1 and twk-16 DVA regulatory elements. Conclusions/Significance: We identified by multi-species conservation regulatory regions within three genes that direct expression in the DVA neuron. We identified four contiguous regions of sequence of the twk-16 gene enhancer with positive and negative effects on expression, which combined to restrict expression to the DVA neuron. For this neuron a single binding site may thus not achieve sufficient specificity for cell specific expression. One of the positive elements, an 8-bp sequence required for expression was identified in silico by sequence comparisons of seven nematode species, demonstrating the potential resolution of expanded multi-species phylogenetic comparisons. C1 [Robinson, Carmie Puckett; Schwarz, Erich M.; Sternberg, Paul W.] CALTECH, Div Biol, Pasadena, CA 91125 USA. [Robinson, Carmie Puckett; Schwarz, Erich M.; Sternberg, Paul W.] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA. [Robinson, Carmie Puckett] Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90033 USA. [Robinson, Carmie Puckett] Univ So Calif, Keck Sch Med, VA Greater Angeles Healthcare Syst, Los Angeles, CA 90033 USA. RP Sternberg, PW (reprint author), CALTECH, Div Biol, Pasadena, CA 91125 USA. EM pws@caltech.edu OI Schwarz, Erich/0000-0003-3151-4381 FU Howard Hughes Medical Insitute; National Institutes of Health [GM084389] FX Funding: Howard Hughes Medical Insitute, with which PWS is an investigator; National Institutes of Health GM084389 (to PWS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 1 Z9 5 U1 1 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 28 PY 2013 VL 8 IS 1 AR e54971 DI 10.1371/journal.pone.0054971 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 093SF UT WOS:000315211500042 ER PT J AU Chen, ZY Shen, HS Luo, MY Duan, CJ Cai, WL Lu, HB Zhang, GP Liu, Y Liang, JZ AF Chen, Zhi-Yuan Shen, He-Song Luo, Ming-Yue Duan, Chai-Jie Cai, Wen-Li Lu, Hong-Bing Zhang, Guo-Peng Liu, Yang Liang, Jerome Z. TI Pilot study on efficacy of reduced cathartic bowel preparation with polyethylene glycol and bisacodyl SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Colorectal cancer; Screening; Computed tomographic colonography; Polyethylene glycol; Bisacodyl ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; CT COLONOGRAPHY; COLORECTAL-CANCER; PATIENT ACCEPTANCE; IMAGE QUALITY; DIAGNOSTIC PERFORMANCE; COLONOSCOPY; REGIMENS; POPULATION; EXPERIENCE AB AIM: To evaluate the efficacy of reduced cathartic bowel preparation with 2 L polyethylene glycol (PEG)-4000 electrolyte solution and 10 mg bisacodyl enteric-coated tablets for computed tomographic colonography (CTC). METHODS: Sixty subjects who gave informed consent were randomly assigned to study group A, study group B or the control group. On the day prior to CTC, subjects in study group A were given 20 mL 40% wt/vol barium sulfate suspension before 3 mealtimes, 60 mL 60% diatrizoate meglumine diluted in 250 mL water after supper, and 10 mg bisacodyl enteric-coated tablets 1 h before oral administration of 2 L PEG-4000 electrolyte solution. Subjects in study group B were treated identically to those in study group A, with the exception of bisacodyl which was given 1 h after oral PEG-4000. Subjects in the control group were managed using the same strategy as the subjects in study group A, but without administration of bisacodyl. Residual stool and fluid scores, the attenuation value of residual fluid, and discomfort during bowel preparation in the three groups were analyzed statistically. RESULTS: The mean scores for residual stool and fluid in study group A were lower than those in study group B, but the differences were not statistically significant. Subjects in study group A showed greater stool and fluid cleansing ability than the subjects in study group B. The mean scores for residual stool and fluid in study groups A and B were lower than those in the control group, and were significantly different. There was no significant difference in the mean attenuation value of residual fluid between study group A, study group B and the control group. The total discomfort index during bowel preparation was 46, 45 and 45 in the three groups, respectively, with no significant difference. CONCLUSION: Administration of 10 mg bisacodyl enteric-coated tablets prior to or after oral administration of 2 L PEG-4000 electrolyte solution enhances stool and fluid cleansing ability, and has no impact on the attenuation value of residual fluid or the discomfort index. The former is an excellent alternative for CTC colorectum cleansing (C) 2013 Baishideng. All rights reserved. C1 [Chen, Zhi-Yuan; Shen, He-Song; Luo, Ming-Yue] Sun Yat Sen Univ, Affiliated Hosp 6, Dept Radiol, Guangzhou 510655, Guangdong, Peoples R China. [Chen, Zhi-Yuan] Guangdong Prov Hosp Tradit Chinese Med, Dept Radiol, Guangzhou 510006, Guangdong, Peoples R China. [Duan, Chai-Jie] Tsinghua Univ, Grad Sch Shenzhen, Biomed Engn Res Ctr, Shenzhen 518055, Guangdong, Peoples R China. [Cai, Wen-Li] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Cai, Wen-Li] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Lu, Hong-Bing; Zhang, Guo-Peng; Liu, Yang] Fourth Mil Med Univ, Dept Biomed Engn, Xian 710032, Shaanxi Provinc, Peoples R China. [Liang, Jerome Z.] SUNY Stony Brook, Dept Radiol, Stony Brook, NY 11794 USA. [Liang, Jerome Z.] SUNY Stony Brook, Dept Comp Sci, Stony Brook, NY 11794 USA. RP Luo, MY (reprint author), Sun Yat Sen Univ, Affiliated Hosp 6, Dept Radiol, Guangzhou 510655, Guangdong, Peoples R China. EM myluo720@163.com FU Guangdong Provincial Science and Technology Program [2011B031800182] FX Supported by Grant from Guangdong Provincial Science and Technology Program, No. 2011B031800182 NR 35 TC 1 Z9 1 U1 0 U2 11 PU BAISHIDENG PUBL GRP CO LTD PI WANCHAI PA ROOM 1701, 17-F, HENAN BUILDING, NO. 90, JAFFE RD, WANCHAI, HONG KONG 100025, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD JAN 28 PY 2013 VL 19 IS 4 BP 561 EP 568 DI 10.3748/wjg.v19.i4.561 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 079ZQ UT WOS:000314211200017 PM 23382637 ER PT J AU Agasti, SS Kohler, RH Liong, M Peterson, VM Lee, H Weissleder, R AF Agasti, Sarit S. Kohler, Rainer H. Liong, Monty Peterson, Vanessa M. Lee, Hakho Weissleder, Ralph TI Dual Imaging and Photoactivated Nanoprobe for Controlled Cell Tracking SO SMALL LA English DT Article DE photoactivation; nanoprobes; cell labeling; targeting; biomarkers ID TUMOR-ASSOCIATED MACROPHAGES; IRON-OXIDE NANOPARTICLES; IN-VIVO; FLUORESCENT PROTEIN; GOLD NANOPARTICLES; SMALL MOLECULES; CANCER-CELLS; TAT PEPTIDE; LIGHT; MICROENVIRONMENT C1 [Agasti, Sarit S.; Kohler, Rainer H.; Liong, Monty; Peterson, Vanessa M.; Lee, Hakho; Weissleder, Ralph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu FU National Institute of Health [R01-EB0044626, R01-EB010011, T32CA79443, P50CA86355]; CCNE [U54CA151884, HHSN268201000044C] FX We thank T. Reiner and G. Budin for helpful discussions with the chemical synthesis; E. Tiglao for assistance with cell culture; A. Zaltsman for assistance with microscopy; N. Sergeyev for synthesis of cross-linked dextran stabilized nanoparticles and Y. Fisher-Jeffes for reviewing the manuscript. This work was supported in part by National Institute of Health Grants R01-EB0044626, R01-EB010011, T32 grant T32CA79443, P50 grant P50CA86355, CCNE contract U54CA151884, and TPEN contract HHSN268201000044C. NR 53 TC 8 Z9 8 U1 3 U2 56 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1613-6810 J9 SMALL JI Small PD JAN 28 PY 2013 VL 9 IS 2 BP 222 EP 227 DI 10.1002/smll.201201007 PG 6 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 074SN UT WOS:000313833800010 PM 22996932 ER PT J AU Demetri, GD Reichardt, P Kang, YK Blay, JY Rutkowski, P Gelderblom, H Hohenberger, P Leahy, M von Mehren, M Joensuu, H Badalamenti, G Blackstein, M Le Cesne, A Schoffski, P Maki, RG Bauer, S Nguyen, BB Xu, JM Nishida, T Chung, J Kappeler, C Kuss, I Laurent, D Casali, PG AF Demetri, George D. Reichardt, Peter Kang, Yoon-Koo Blay, Jean-Yves Rutkowski, Piotr Gelderblom, Hans Hohenberger, Peter Leahy, Michael von Mehren, Margaret Joensuu, Heikki Badalamenti, Giuseppe Blackstein, Martin Le Cesne, Axel Schoffski, Patrick Maki, Robert G. Bauer, Sebastian Binh Bui Nguyen Xu, Jianming Nishida, Toshirou Chung, John Kappeler, Christian Kuss, Iris Laurent, Dirk Casali, Paolo G. CA GRID Study Investigators TI Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial SO LANCET LA English DT Article ID TYROSINE KINASE INHIBITOR; ADJUVANT IMATINIB; GROWTH-FACTOR; IN-VIVO; RESISTANCE; KIT; MUTATIONS; MECHANISMS; MESYLATE; SU11248 AB Background Until now, only imatinib and sunitinib have proven clinical benefit in patients with gastrointestinal stromal tumours (GIST), but almost all metastatic GIST eventually develop resistance to these agents, resulting in fatal disease progression. We aimed to assess efficacy and safety of regorafenib in patients with metastatic or unresectable GIST progressing after failure of at least imatinib and sunitinib. Methods We did this phase 3 trial at 57 hospitals in 17 countries. Patients with histologically confirmed, metastatic or unresectable GIST, with failure of at least previous imatinib and sunitinib were randomised in a 2:1 ratio (by computer-generated randomisation list and interactive voice response system; preallocated block design (block size 12); stratified by treatment line and geographical region) to receive either oral regorafenib 160 mg daily or placebo, plus best supportive care in both groups, for the first 3 weeks of each 4 week cycle. The study sponsor, participants, and investigators were masked to treatment assignment. The primary endpoint was progression-free survival (PFS). At disease progression, patients assigned placebo could crossover to open-label regorafenib. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01271712. Results From Jan 4, to Aug 18, 2011, 240 patients were screened and 199 were randomised to receive regorafenib (n=133) or matching placebo (n=66). Data cutoff was Jan 26, 2012. Median PFS per independent blinded central review was 4.8 months (IQR 1.4-9.2) for regorafenib and 0.9 months (0.9-1.8) for placebo (hazard ratio [HR] 0.27, 95% CI 0.19-0.39; p<0.0001). After progression, 56 patients (85%) assigned placebo crossed over to regorafenib. Drug-related adverse events were reported in 130 (98%) patients assigned regorafenib and 45 (68%) patients assigned placebo. The most common regorafenib-related adverse events of grade 3 or higher were hypertension (31 of 132, 23%), hand-foot skin reaction (26 of 132, 20%), and diarrhoea (seven of 132, 5%). Interpretation The results of this study show that oral regorafenib can provide a significant improvement in progression-free survival compared with placebo in patients with metastatic GIST after progression on standard treatments. As far as we are aware, this is the first clinical trial to show benefit from a kinase inhibitor in this highly refractory population of patients. C1 [Demetri, George D.] Dana Farber Canc Inst, Ludwig Ctr, Boston, MA 02215 USA. [Demetri, George D.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Reichardt, Peter] HELIOS Klinikum Bad Saarow, Dept Hematol Oncol & Palliat Med, Bad Saarow Pieskow, Germany. [Kang, Yoon-Koo] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Oncol, Seoul, South Korea. [Blay, Jean-Yves] Ctr Leon Berard, F-69373 Lyon, France. [Blay, Jean-Yves] Univ Lyon 1, F-69365 Lyon, France. [Rutkowski, Piotr] Maria Sklodowska Curie Mem Canc Ctr, Dept Soft Tissue Bone Sarcoma & Melanoma, Warsaw, Poland. [Rutkowski, Piotr] Inst Oncol, Warsaw, Poland. [Gelderblom, Hans] Leiden Univ, Med Ctr, Dept Clin Oncol, Leiden, Netherlands. [Hohenberger, Peter] Univ Hosp Mannheim, Div Surg Oncol & Thorac Surg, Mannheim, Germany. [Leahy, Michael] Christie NHS Fdn Trust, Manchester, Lancs, England. [von Mehren, Margaret] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Joensuu, Heikki] Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki, Finland. [Badalamenti, Giuseppe] Univ Palermo, Dept Oncol, Palermo, Italy. [Blackstein, Martin] Mt Sinai Hosp, Med Oncol Unit, Toronto, ON M5G 1X5, Canada. [Le Cesne, Axel] Inst Gustave Roussy, Dept Med, Paris, France. [Schoffski, Patrick] Katholieke Univ Leuven Hosp, Dept Gen Med Oncol, Louvain, Belgium. [Maki, Robert G.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Bauer, Sebastian] Univ Duisburg Essen, Sarcoma Ctr, W German Canc Ctr, Essen, Germany. [Binh Bui Nguyen] Bergonie Inst, Bordeaux, France. [Xu, Jianming] Acad Mil Med Sci, Affiliated Hosp Canc Ctr, Beijing, Peoples R China. [Nishida, Toshirou] Osaka Police Hosp, Dept Surg, Osaka, Japan. [Chung, John] Bayer Healthcare Pharmaceut, Wayne, NJ USA. [Kappeler, Christian; Kuss, Iris; Laurent, Dirk] Bayer Pharma AG, Berlin, Germany. [Casali, Paolo G.] Fdn IRCCS Ist Nazl Tumori, Milan, Italy. RP Demetri, GD (reprint author), Dana Farber Canc Inst, Ludwig Ctr, Boston, MA 02215 USA. EM gdemetri@partners.org RI Rutkowski, Piotr/B-3907-2013; Leahy, Michael/K-8697-2015; van der Graaf, Winette/A-5006-2014; Blay, Jean-Yves/N-3966-2016; casali, Paolo Giovanni/D-1524-2017 OI Joensuu, Heikki/0000-0003-0281-2507; Leahy, Michael/0000-0002-9936-0537; Rutkowski, Piotr/0000-0002-8920-5429; Blay, Jean-Yves/0000-0001-7190-120X; casali, Paolo Giovanni/0000-0003-4056-8023 FU Bayer HealthCare Pharmaceuticals; Virginia and Daniel K Ludwig Trust for Cancer Research; Team Russo; Paul's Posse; Pan Mass Challenge; US National Cancer Institute [1P50CA127003-05] FX We thank the participating patients and staff at each of the study centres. The trial was supported by Bayer HealthCare Pharmaceuticals. Administrative and minor editorial assistance in the preparation of this report was provided by Succinct Healthcare Communications, with financial support from Bayer HealthCare Pharmaceuticals; the authors retained complete editorial control over the content. Additional support for this work has been provided to GDD from the following sources: The Virginia and Daniel K Ludwig Trust for Cancer Research, Team Russo, Paul's Posse and the Pan Mass Challenge, and Gastrointestinal Cancer SPORE Grant 1P50CA127003-05 from the US National Cancer Institute. NR 33 TC 280 Z9 296 U1 6 U2 83 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD JAN 26 PY 2013 VL 381 IS 9863 BP 295 EP 302 DI 10.1016/S0140-6736(12)61857-1 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 077IT UT WOS:000314021800026 PM 23177515 ER PT J AU Rakovic, A Shurkewitsch, K Seibler, P Grunewald, A Zanon, A Hagenah, J Krainc, D Klein, C AF Rakovic, Aleksandar Shurkewitsch, Katharina Seibler, Philip Gruenewald, Anne Zanon, Alessandra Hagenah, Johann Krainc, Dimitri Klein, Christine TI Phosphatase and Tensin Homolog (PTEN)-induced Putative Kinase 1 (PINK1)-dependent Ubiquitination of Endogenous Parkin Attenuates Mitophagy STUDY IN HUMAN PRIMARY FIBROBLASTS AND INDUCED PLURIPOTENT STEM CELL-DERIVED NEURONS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MITOCHONDRIAL DEPOLARIZATION; DAMAGED MITOCHONDRIA; PROTEIN-DEGRADATION; PINK1; NEURONS; PROTEASOME; DISEASE; TRANSLOCATION; MITOFUSIN; MUTANT AB Mutations in the E3 ubiquitin ligase Parkin and the mitochondrial PTEN-induced putative kinase 1 (PINK1) have been identified to cause autosomal recessive forms of familial Parkinson disease, with PINK1 functioning upstream of Parkin in a pathway important for the maintenance of mitochondrial function and morphology. Upon the loss of the mitochondrial membrane potential, Parkin translocates to mitochondria in a PINK1-dependent manner to ubiquitinate mitochondrial proteins. Parkin-mediated polyubiquitination of outer mitochondrial membrane (OMM) proteins recruits the ubiquitin-and LC3-binding adaptor protein p62 to mitochondria and induces mitophagy. Although previous studies examined mitophagy in established cell lines through overexpression approaches, there is an imperative to study the role of endogenous Parkin and PINK1 in human-derived and biologically relevant cell models. Here, we demonstrate in human primary fibroblasts and induced pluripotent stem-derived neurons from controls and PINK1 mutation carriers that endogenous levels of Parkin are not sufficient to initiate mitophagy upon loss of the mitochondrial membrane potential, caused by its (self-) ubiquitination, followed by degradation via the ubiquitin proteasome system. Next, we showed differential PINK1-dependent, Parkin-mediated ubiquitination of OMM proteins, which is Parkin dose-dependent and affects primarily OMM proteins of higher molecular mass. In contrast to the situation fibroblasts, we did not detect mitophagy in induced pluripotent stem-derived neurons even upon overexpression of Parkin. Taken together, our data demonstrate that mitophagy differs between human non-neuronal and neuronal cells and between "endogenous" and "Parkin-overexpressing" cellular models. C1 [Rakovic, Aleksandar; Shurkewitsch, Katharina; Seibler, Philip; Gruenewald, Anne; Zanon, Alessandra; Hagenah, Johann; Klein, Christine] Med Univ Lubeck, Dept Neurol, Sect Clin & Mol Neurogenet, D-23562 Lubeck, Germany. [Hagenah, Johann] Med Univ Lubeck, Dept Neurol, D-23562 Lubeck, Germany. [Zanon, Alessandra] Europian Acad Bozen, Ctr Biomed, I-39100 Bolzano, Italy. [Krainc, Dimitri] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. RP Klein, C (reprint author), Med Univ Lubeck, Dept Neurol, Sect Clin & Mol Neurogenet, Maria Goeppert Str 1, D-23562 Lubeck, Germany. EM christine.klein@neuro.uni-luebeck.de FU Fritz Thyssen Foundation; National Genome Research Network-plus (Federal Ministry of Education and Research); EU Grant European Project on Mendelian Forms of Parkinson's Disease (FP7); Hermann and Lilly Schilling Foundation FX This work was supported by the Fritz Thyssen Foundation (to A. G.), National Genome Research Network-plus (Federal Ministry of Education and Research, to C. K.), and EU Grant European Project on Mendelian Forms of Parkinson's Disease (FP7).; Recipient of a career development award from the Hermann and Lilly Schilling Foundation. To whom correspondence should be addressed: Section of Clinical and Molecular Neurogenetics at the Dept. of Neurology, Maria-Goeppert-Str. 1, 23562 Lubeck, Germany. Tel.: 494512903351; Fax: 494512903355; E-mail: christine.klein@neuro.uni-luebeck.de. NR 35 TC 67 Z9 69 U1 0 U2 13 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 25 PY 2013 VL 288 IS 4 BP 2223 EP 2237 DI 10.1074/jbc.M112.391680 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 079ZS UT WOS:000314211500013 PM 23212910 ER PT J AU Zhang, ZC Gutierrez, D Li, X Bidlack, F Cao, HJ Wang, JB Andrade, K Margolis, HC Amendt, BA AF Zhang, Zichao Gutierrez, Diana Li, Xiao Bidlack, Felicitas Cao, Huojun Wang, Jianbo Andrade, Kelsey Margolis, Henry C. Amendt, Brad A. TI The LIM Homeodomain Transcription Factor LHX6 A TRANSCRIPTIONAL REPRESSOR THAT INTERACTS WITH PITUITARY HOMEOBOX 2 (PITX2) TO REGULATE ODONTOGENESIS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DOMAIN INTERACTOR NLI; DENTAL EPITHELIUM; FLUORESCENCE COMPLEMENTATION; AMELOGENESIS IMPERFECTA; FUNCTIONAL INTERACTIONS; INTERNEURON SUBTYPES; CELL-PROLIFERATION; TOOTH DEVELOPMENT; RIEGER-SYNDROME; HOMEOBOX GENES AB LHX6 is a LIM-homeobox transcription factor expressed during embryogenesis; however, the molecular mechanisms regulating LHX6 transcriptional activities are unknown. LHX6 and the PITX2 homeodomain transcription factor have overlapping expression patterns during tooth and craniofacial development, and in this report, we demonstrate new transcriptional mechanisms for these factors. PITX2 and LHX6 are co-expressed in the oral and dental epithelium and epithelial cell lines. Lhx6 expression is increased in Pitx2c transgenic mice and decreased in Pitx2 null mice. PITX2 activates endogenous Lhx6 expression and the Lhx6 promoter, whereas LHX6 represses its promoter activity. Chromatin immunoprecipitation experiments reveal endogenous PITX2 binding to the Lhx6 promoter. LHX6 directly interacts with PITX2 to inhibit PITX2 transcriptional activities and activation of multiple promoters. Bimolecular fluorescence complementation assays reveal an LHX6.PITX2 nuclear interaction in living cells. LHX6 has a dominant repressive effect on the PITX2 synergistic activation with LEF-1 and beta-catenin co-factors. Thus, LHX6 acts as a transcriptional repressor and represses the expression of several genes involved in odontogenesis. We have identified specific defects in incisor, molar, mandible, bone, and root development and late stage enamel formation in Lhx6 null mice. Amelogenin and ameloblastin expression is reduced and/or delayed in the Lhx6 null mice, potentially resulting from defects in dentin deposition and ameloblast differentiation. Our results demonstrate that LHX6 regulates cell proliferation in the cervical loop and promotes cell differentiation in the anterior region of the incisor. We demonstrate new molecular mechanisms for LHX6 and an interaction with PITX2 for normal craniofacial and tooth development. C1 [Zhang, Zichao; Gutierrez, Diana; Li, Xiao; Cao, Huojun; Wang, Jianbo; Andrade, Kelsey; Amendt, Brad A.] Texas A&M Univ, Hlth Sci Ctr, Ctr Environm & Genet Med, Inst Biosci & Technol, Houston, TX 77030 USA. [Bidlack, Felicitas; Margolis, Henry C.] Forsyth Inst, Dept Biomineralizat, Boston, MA 02142 USA. RP Amendt, BA (reprint author), Univ Iowa, Craniofacial Anomalies Res Ctr, 1-675 BSB,51 Newton Rd, Iowa City, IA 52242 USA. EM brad-amendt@uiowa.edu FU National Institutes of Health [DE13941, DE18885, DE016376] FX This work was supported, in whole or in part, by National Institutes of Health Grants DE13941 and DE18885 (to B. A. A.) and DE016376 (to H. C. M.). NR 54 TC 11 Z9 11 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 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 25 PY 2013 VL 288 IS 4 BP 2485 EP 2500 DI 10.1074/jbc.M112.402933 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 079ZS UT WOS:000314211500035 PM 23229549 ER PT J AU Basset, A Zhang, F Benes, C Sayeed, S Herd, M Thompson, C Golenbock, DT Camilli, A Malley, R AF Basset, Alan Zhang, Fan Benes, Cyril Sayeed, Sabina Herd, Muriel Thompson, Claudette Golenbock, Douglas T. Camilli, Andrew Malley, Richard TI Toll-like Receptor (TLR) 2 Mediates Inflammatory Responses to Oligomerized RrgA Pneumococcal Pilus Type 1 Protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; STREPTOCOCCUS-PNEUMONIAE; NASOPHARYNGEAL COLONIZATION; ELICIT PROTECTION; CONJUGATE VACCINE; FUSION PROTEIN; CUTTING EDGE; INFECTION; MICE; PNEUMOLYSIN AB The pneumococcal type 1 pilus is an inflammatory and adherence-promoting structure associated with increased virulence in mouse models. We show that RrgA, an ancillary pilus subunit devoid of a lipidation motif, particularly when presented as part of an oligomer, is a TLR2 agonist. The surface-exposed domain III, and in particular a 49-amino acid sequence (P3), of the protein is responsible for the TLR2 activity of RrgA. A pneumococcal mutant carrying RrgA with a deletion of the P3 region was significantly reduced in its ability to activate TLR2 and induce TNF-alpha responses after mouse intraperitoneal infection, whereas no such difference could be noted when TLR2(-/-) mice were challenged, further implicating this region in recognition by TLR2. Thus, we conclude that the type 1 pneumococcal pilus can activate cells via TLR2, and the ancillary pilus subunit RrgA is a key component of this activation. C1 [Basset, Alan; Zhang, Fan; Sayeed, Sabina; Herd, Muriel; Malley, Richard] Childrens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA. [Benes, Cyril] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Thompson, Claudette] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 01225 USA. [Golenbock, Douglas T.] Univ Massachusetts, Med Ctr, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01655 USA. [Camilli, Andrew] Tufts Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02111 USA. [Camilli, Andrew] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. RP Malley, R (reprint author), Childrens Hosp, Dept Med, Div Infect Dis, Enders 861-4,300 Longwood Ave, Boston, MA 02115 USA. EM richard.malley@childrens.harvard.edu FU National Institutes of Health [R01 AI066013]; Children's Hospital, Boston FX This work was supported, in whole or in part, by National Institutes of Health Grant R01 AI066013 (to R. M.).; Supported by the Translational Research Program at Children's Hospital, Boston. To whom correspondence should be addressed: Division of Infectious Diseases, Boston Children's Hospital, Enders 861.4, 300 Longwood Ave., Boston, MA 02115. Tel.: 617-919-2902; Fax: 617-730-0255; E-mail: richard.malley@childrens.harvard.edu. NR 51 TC 18 Z9 18 U1 0 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 25 PY 2013 VL 288 IS 4 BP 2665 EP 2675 DI 10.1074/jbc.M112.398875 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 079ZS UT WOS:000314211500051 PM 23233677 ER PT J AU Meissner, HI Glasgow, RE Vinson, CA Chambers, D Brownson, RC Green, LW Ammerman, AS Weiner, BJ Mittman, B AF Meissner, Helen I. Glasgow, Russell E. Vinson, Cynthia A. Chambers, David Brownson, Ross C. Green, Lawrence W. Ammerman, Alice S. Weiner, Bryan J. Mittman, Brian TI The US training institute for dissemination and implementation research in health SO IMPLEMENTATION SCIENCE LA English DT Article DE Training; Dissemination; Implementation ID KNOWLEDGE TRANSLATION; SCIENCE; FRAMEWORK AB Background: The science of dissemination and implementation (D&I) is advancing the knowledge base for how best to integrate evidence-based interventions within clinical and community settings and how to recast the nature or conduct of the research itself to make it more relevant and actionable in those settings. While the field is growing, there are only a few training programs for D&I research; this is an important avenue to help build the field's capacity. To improve the United States' capacity for D&I research, the National Institutes of Health and Veterans Health Administration collaborated to develop a five-day training institute for postdoctoral level applicants aspiring to advance this science. Methods: We describe the background, goals, structure, curriculum, application process, trainee evaluation, and future plans for the Training in Dissemination and Implementation Research in Health (TIDIRH). Results: The TIDIRH used a five-day residential immersion to maximize opportunities for trainees and faculty to interact. The train-the-trainer-like approach was intended to equip participants with materials that they could readily take back to their home institutions to increase interest and further investment in D&I. The TIDIRH curriculum included a balance of structured large group discussions and interactive small group sessions. Thirty-five of 266 applicants for the first annual training institute were accepted from a variety of disciplines, including psychology (12 trainees); medicine (6 trainees); epidemiology (5 trainees); health behavior/health education (4 trainees); and 1 trainee each from education & human development, health policy and management, health services research, public health studies, public policy and social work, with a maximum of two individuals from any one institution. The institute was rated as very helpful by attendees, and by six months after the institute, a follow-up survey (97% return rate) revealed that 72% had initiated a new grant proposal in D&I research; 28% had received funding, and 77% had used skills from TIDIRH to influence their peers from different disciplines about D&I research through building local research networks, organizing formal presentations and symposia, teaching and by leading interdisciplinary teams to conduct D&I research. Conclusions: The initial TIDIRH training was judged successful by trainee evaluation at the conclusion of the week's training and six-month follow-up, and plans are to continue and possibly expand the TIDIRH in coming years. Strengths are seen as the residential format, quality of the faculty and their flexibility in adjusting content to meet trainee needs, and the highlighting of concrete D&I examples by the local host institution, which rotates annually. Lessons learned and plans for future TIDIRH trainings are summarized. C1 [Meissner, Helen I.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. [Glasgow, Russell E.; Vinson, Cynthia A.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA. [Chambers, David] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. [Brownson, Ross C.] Washington Univ, Sch Med, St Louis, MO USA. [Green, Lawrence W.] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA USA. [Ammerman, Alice S.] Univ N Carolina, Gillings Sch Publ Hlth, Ctr Hlth Promot & Dis Prevent, Chapel Hill, NC USA. [Weiner, Bryan J.] Univ N Carolina, Dept Hlth Policy & Management, Gillings Sch Publ Hlth, Chapel Hill, NC USA. [Mittman, Brian] VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. RP Meissner, HI (reprint author), NIH, Off Behav & Social Sci Res, Bldg 10, Bethesda, MD 20892 USA. EM meissneh@od.nih.gov OI Mittman, Brian/0000-0003-3589-9178 FU NIDDK NIH HHS [P30 DK092950] NR 14 TC 34 Z9 34 U1 5 U2 21 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD JAN 24 PY 2013 VL 8 AR 12 DI 10.1186/1748-5908-8-12 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 137DC UT WOS:000318414200003 PM 23347882 ER PT J AU Ganis, G Schendan, HE AF Ganis, Giorgio Schendan, Haline E. TI Concealed semantic and episodic autobiographical memory electrified SO FRONTIERS IN HUMAN NEUROSCIENCE LA English DT Article DE concealed information; deception; deception detection; ERPs (event-related potentials); semantic memory; episodic memory ID EVENT-RELATED POTENTIALS; GUILTY KNOWLEDGE TEST; MEDIAL TEMPORAL-LOBE; FUNCTIONAL MAGNETIC-RESONANCE; VISUAL OBJECT IDENTIFICATION; PERCEPTUAL DECISION-MAKING; CONSCIOUS RECOLLECTION; RECOGNITION MEMORY; BRAIN POTENTIALS; MENTAL CHRONOMETRY AB Electrophysiology-based concealed information tests (CIT) try to determine whether somebody possesses concealed information about a crime-related item (probe) by comparing event related potentials (ERPs) between this item and comparison items (irrelevants). Although the broader field is sometimes referred to as "memory detection," little attention has been paid to the precise type of underlying memory involved. This study begins addressing this issue by examining the key distinction between semantic and episodic memory in the autobiographical domain within a CIT paradigm. This study also addresses the issue of whether multiple repetitions of the items over the course of the session habituate the brain responses. Participants were tested in a 3-stimulus CIT with semantic autobiographical probes (their own date of birth) and episodic autobiographical probes (a secret date learned just before the study). Results dissociated these two memory conditions on several ERP components. Semantic probes elicited a smaller frontal N2 than episodic probes, consistent with the idea that the frontal N2 decreases with greater pre-existing knowledge about the item. Likewise, semantic probes elicited a smaller central N400 than episodic probes. Semantic probes also elicited a larger P3b than episodic probes because of their richer meaning. In contrast, episodic probes elicited a larger late positive complex (LPC) than semantic probes, because of the recent episodic memory associated with them. All these ERPs showed a difference between probes and irrelevants in both memory conditions, except for the N400, which showed a difference only in the semantic condition. Finally, although repetition affected the ERPs, it did not reduce the difference between probes and irrelevants. These findings show that the type of memory associated with a probe has both theoretical and practical importance for CIT research. C1 [Ganis, Giorgio; Schendan, Haline E.] Univ Plymouth, Cognit Inst, Sch Psychol, Plymouth PL4 8AA, Devon, England. [Ganis, Giorgio; Schendan, Haline E.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Ganis, Giorgio] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Ganis, G (reprint author), Univ Plymouth, Cognit Inst, Sch Psychol, Plymouth PL4 8AA, Devon, England. EM ganis@nmr.mgh.harvard.edu OI Ganis, Giorgio/0000-0001-6175-2618; Schendan, Haline/0000-0001-8925-5605 FU UoP International Research, Networking and Collaboration Award; Marie Curie Career Integration Grant (CoND) FX Giorgio Ganis and Haline Schendan contributed equally to this work. We would like to thank Leanne Kiff for assistance with data collection. This research was supported in part by a UoP International Research, Networking and Collaboration Award, and by a Marie Curie Career Integration Grant (CoND) to Giorgio Ganis. NR 102 TC 3 Z9 3 U1 0 U2 22 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5161 J9 FRONT HUM NEUROSCI JI Front. Hum. Neurosci. PD JAN 24 PY 2013 VL 6 AR 354 DI 10.3389/fnhum.2012.00354 PG 21 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 079KR UT WOS:000314169500001 ER PT J AU Macias, CE Bodugoz-Senturk, H Muratoglu, OK AF Macias, Celia E. Bodugoz-Senturk, Hatice Muratoglu, Orhun K. TI Quantification of PVA hydrogel dissolution in water and bovine serum SO POLYMER LA English DT Article DE Hydrogel; PVA; Cartilage ID AUTOLOGOUS CHONDROCYTE IMPLANTATION; SEMICRYSTALLINE POLY(VINYL ALCOHOL); H ARTIFICIAL MENISCUS; POLY-VINYL ALCOHOL; POLYVINYL-ALCOHOL; CARTILAGE DEFECTS; RANDOMIZED-TRIAL; KNEE; MICROFRACTURE; TRANSPLANTATION AB Poly(vinyl alcohol) (PVA) hydrogel is a candidate biomaterial for orthopaedic applications such as cartilage resurfacing due to its viscoelastic nature, high water content, and biocompatibility. PVA is not assumed to be biodegradable; however, depending on the level of physical and/or chemical crosslinking it may illicit dissolution either during storage in water or during in vivo use when articulating against cartilage. In addition, gravimetric quantification of wear during pre-clinical wear testing of a PVA-based implant is challenging due to unpredictable changes in water content. Our aim was to develop a method to detect dissolved PVA in water and bovine serum; bovine serum is the lubricant of choice for preclinical wear testing of orthopaedic implants. We used iodine complexation to determine PVA concentration in solution using UV-Vis spectrophotometry. We further refined this method to determine the effects of PVA molecular weight and the presence of poly(ethylene glycol) (PEG) that may be used in the fabrication of the gel. In addition, we developed a method for determining the amount of PVA dissolved in bovine serum to quantify the extent of PVA dissolution during pre-clinical wear studies. We were able to detect PVA in solution with concentrations as low as 10(-5) g/mL and created calibration curves for different solvents, i.e. water and bovine serum. Based on the calibrations, we quantified the dissolution behavior of PVA in water at 40 degrees C during a six month period and found that the dissolution from an untreated PVA hydrogel is 3 x 10(4) ppm, and could be lowered to 1 x 10(3) ppm by dehydration and/or annealing of the PVA hydrogel. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Muratoglu, Orhun K.] Massachusetts Gen Hosp, Harris Orthopaed Biomech & Biomat Lab, Dept Orthopaed Surg, Boston, MA 02114 USA. [Bodugoz-Senturk, Hatice; Muratoglu, Orhun K.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Biomech & Biomat Lab, Dept Orthopaed Surg, 55 Fruit St,GRJ 1206, Boston, MA 02114 USA. EM omuratoglu@partners.org FU Zimmer, Inc. FX This study was funded by departmental research funds and by a sponsored research grant from Zimmer, Inc. NR 37 TC 7 Z9 7 U1 8 U2 61 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0032-3861 J9 POLYMER JI Polymer PD JAN 24 PY 2013 VL 54 IS 2 BP 724 EP 729 DI 10.1016/j.polymer.2012.11.068 PG 6 WC Polymer Science SC Polymer Science GA 078FV UT WOS:000314085000031 ER PT J AU Chang, SY Song, JH Guleng, B Cotoner, CA Arihiro, S Zhao, Y Chiang, HS O'Keeffe, M Liao, GX Karp, CL Kweon, MN Sharpe, AH Bhan, A Terhorst, C Reinecker, HC AF Chang, Sun-Young Song, Joo-Hye Guleng, Bayasi Cotoner, Carmen Alonso Arihiro, Seiji Zhao, Yun Chiang, Hao-Sen O'Keeffe, Michael Liao, Gongxian Karp, Christopher L. Kweon, Mi-Na Sharpe, Arlene H. Bhan, Atul Terhorst, Cox Reinecker, Hans-Christian TI Circulatory Antigen Processing by Mucosal Dendritic Cells Controls CD8(+) T Cell Activation SO IMMUNITY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; INTESTINAL CAPILLARIES; ORAL TOLERANCE; LAMINA-PROPRIA; IN-VIVO; PERMEABILITY; HOMEOSTASIS; AUTOIMMUNE; TRANSPORT; RAT AB Circulatory antigens transit through the small intestine via the fenestrated capillaries in the lamina propria prior to entering into the draining lymphatics. But whether or how this process controls mucosal immune responses remains unknown. Here we demonstrate that dendritic cells (DCs) of the lamina propria can sample and process both circulatory and lumina! antigens. Surprisingly, antigen cross-presentation by resident CX3CR1(+) DCs induced differentiation of precursor cells into CD8(+) T cells that expressed interleukin-10 (IL-10), IL-13, and IL-9 and could migrate into adjacent compartments. We conclude that lamina propria CX3CR1(+) DCs facilitate the surveillance of circulatory antigens and act as a conduit for the processing of self- and intestinally absorbed antigens, leading to the induction of CD8(+) T cells, that partake in the control of T cell activation during mucosal immune responses. C1 [Chang, Sun-Young; Song, Joo-Hye; Guleng, Bayasi; Cotoner, Carmen Alonso; Arihiro, Seiji; Zhao, Yun; Chiang, Hao-Sen; Reinecker, Hans-Christian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Gastrointestinal Unit, Boston, MA 02114 USA. [Chang, Sun-Young; Song, Joo-Hye; Guleng, Bayasi; Cotoner, Carmen Alonso; Arihiro, Seiji; Zhao, Yun; Chiang, Hao-Sen; Reinecker, Hans-Christian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Bhan, Atul] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [O'Keeffe, Michael; Liao, Gongxian] Beth Israel Deaconess Med Ctr, Div Immunol, Boston, MA 02115 USA. [O'Keeffe, Michael; Liao, Gongxian] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Karp, Christopher L.; Terhorst, Cox] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Res Fdn, Div Mol Immunol, Cincinnati, OH 45229 USA. [Kweon, Mi-Na] Int Vaccine Inst, Mucosal Immunol Sect, Seoul 151818, South Korea. [Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Microbiol, Boston, MA 02115 USA. RP Reinecker, HC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Gastrointestinal Unit, Boston, MA 02114 USA. EM hans-christian_reinecker@hms.havard.edu RI Alonso-Cotoner, Carmen/N-7057-2014; OI Alonso-Cotoner, Carmen/0000-0002-3483-2919; Karp, Christopher/0000-0002-0832-2659; CHIANG, HAO-SEN/0000-0001-5041-9705 FU National Institutes of Health [DK-068181, DK-033506, AI093588, DK-043351, AI-057992, DK-52510] FX Author contributions were as follows: S.Y.C., J.-H.S., B.G., C.A.C., S.A., Y.Z., H.-S.C., M.O., and G.L. carried out experiments; M.-N.K. and A.B. provided pathology advice in the assessments of colitis; C.L.K., A.H.S., and C.T. developed research tools and mice; and H.-C.R. directed the research. This work was supported by grants DK-068181 (H.-C.R.), DK-033506 (H.-C.R.), AI093588 (H.-C.R.), DK-043351 (H.-C.R., C.T.), AI-057992 (C.L.K.), and DK-52510 (C.T.) from the National Institutes of Health. NR 46 TC 34 Z9 36 U1 0 U2 16 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JAN 24 PY 2013 VL 38 IS 1 BP 153 EP 165 DI 10.1016/j.immuni.2012.09.018 PG 13 WC Immunology SC Immunology GA 079TQ UT WOS:000314195500017 PM 23246312 ER PT J AU Steele, DJR Kasmar, AG Guimaraes, AR Dekker, JP AF Steele, David J. R. Kasmar, Anne G. Guimaraes, Alexander R. Dekker, John P. TI Case 3-2013: A 72-Year-Old Woman with Abdominal Pain and Distention after Peritoneal Dialysis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID STAGE RENAL-DISEASE; OF-THE-LITERATURE; TUBERCULOUS PERITONITIS; SIMILAR OUTCOMES; ASCITIC FLUID; HEMODIALYSIS; DIAGNOSIS; FAILURE C1 [Steele, David J. R.] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Kasmar, Anne G.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Guimaraes, Alexander R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Dekker, John P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Guimaraes, Alexander R.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Dekker, John P.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Steele, DJR (reprint author), Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. FU NIAID NIH HHS [K08 AI089858] NR 28 TC 1 Z9 1 U1 0 U2 7 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 24 PY 2013 VL 368 IS 4 BP 375 EP 385 DI 10.1056/NEJMcpc1208142 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 075KX UT WOS:000313885900012 PM 23343067 ER PT J AU Roychaudhuri, R Yang, MF Deshpande, A Cole, GM Frautschy, S Lomakin, A Benedek, GB Teplow, DB AF Roychaudhuri, Robin Yang, Mingfeng Deshpande, Atul Cole, Gregory M. Frautschy, Sally Lomakin, Aleksey Benedek, George B. Teplow, David B. TI C-Terminal Turn Stability Determines Assembly Differences between A beta 40 and A beta 42 SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article ID AMYLOID-BETA-PROTEIN; ALZHEIMERS-DISEASE; A-BETA; CROSS-LINKING; SECONDARY STRUCTURE; SENILE PLAQUES; FIBRILS; OLIGOMERIZATION; PEPTIDES; NMR AB Oligomerization of the amyloid beta-protein (A beta) is a seminal event in Alzheimer's disease. A beta 42, which is only two amino acids longer than A beta 40, is particularly pathogenic. Why this is so has not been elucidated fully. We report here results of computational and experimental studies revealing a C-terminal turn at Val36-Gly37 in A beta 42 that is not present in A beta 40. The dihedral angles of residues 36 and 37 in an Ile31-Ala42 peptide were consistent with beta-turns, and a beta-hairpin-like structure was indeed observed that was stabilized by hydrogen bonds and by hydrophobic interactions between residues 31-35 and residues 38-42. In contrast, A beta(31-40) mainly existed as a statistical coil. To study the system experimentally, we chemically synthesized A beta peptides containing amino acid substitutions designed to stabilize or destabilize the hairpin. The triple substitution Gly33Val-Va136Pro-Gly38Val ("VPV") facilitated A beta 42 hexamer and nonamer formation, while inhibiting formation of classical amyloid-type fibrils. These assemblies were as toxic as were assemblies from wild-type A beta 42. When substituted into A beta 40, the VPV substitution caused the peptide to oligomerize similarly to A beta 42. The modified A beta 40 was significantly more toxic than A beta 40. The double substitution D-Pro36-L-Pro37 abolished hexamer and dodecamer formation by A beta 42 and produced an oligomer size distribution similar to that of A beta 40. Our data suggest that the Va136-Gly37 turn could be the sine qua non of A beta 42. If true, this structure would be an exceptionally important therapeutic target. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Roychaudhuri, Robin; Yang, Mingfeng] Univ Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Deshpande, Atul; Cole, Gregory M.; Frautschy, Sally] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. [Deshpande, Atul; Cole, Gregory M.; Frautschy, Sally] Greater Los Angeles Vet Affairs Healthcare Syst, Geriatr Res Educ & Clin Ctr, Sepulveda, CA 91343 USA. [Lomakin, Aleksey; Benedek, George B.] MIT, Ctr Mat Sci & Engn, Cambridge, MA 02139 USA. [Lomakin, Aleksey; Benedek, George B.] MIT, Dept Phys, Cambridge, MA 02139 USA. [Teplow, David B.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. [Teplow, David B.] Univ Calif Los Angeles, Inst Mol Biol, David Geffen Sch Med, Mary S Easton Ctr Alzheimers Dis Res, Los Angeles, CA 90095 USA. [Teplow, David B.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA. RP Teplow, DB (reprint author), Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. EM dteplow@ucla.edu FU State of California Alzheimer's Disease Research Fund [07-65806]; UCLA Faculty Research Fund; National Institutes of Health [AG027818, NS038328]; Jim Easton Consortium for Alzheimer's Drug Discovery and Biomarkers FX We thank Margaret Condron for synthesizing all the peptides used here. We gratefully acknowledge grants from the State of California Alzheimer's Disease Research Fund (No. 07-65806), UCLA Faculty Research Fund, the National Institutes of Health (AG027818, NS038328), and the Jim Easton Consortium for Alzheimer's Drug Discovery and Biomarkers. NR 66 TC 30 Z9 31 U1 1 U2 46 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JAN 23 PY 2013 VL 425 IS 2 BP 292 EP 308 DI 10.1016/j.jmb.2012.11.006 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 095AA UT WOS:000315305700008 PM 23154165 ER PT J AU Mata-Fink, J Kriegsman, B Yu, HX Zhu, HN Hanson, MC Irvine, DJ Wittrup, KD AF Mata-Fink, Jordi Kriegsman, Barry Yu, Hui Xin Zhu, Hanna Hanson, Melissa C. Irvine, Darrell J. Wittrup, K. Dane TI Rapid Conformational Epitope Mapping of Anti-gp120 Antibodies with a Designed Mutant Panel Displayed on Yeast SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODY; GROWTH-FACTOR RECEPTOR; HIV VACCINE DESIGN; CD4 BINDING-SITE; CONSERVED NEUTRALIZATION EPITOPES; GP120 ENVELOPE GLYCOPROTEIN; WEST-NILE-VIRUS; SURFACE DISPLAY; TYPE-1 GP120 AB gp120 is a substrate for protein engineering both for human immunodeficiency virus (HIV) immunogen design and as a bait for isolating anti-HIV antibodies from patient samples. In this work, we describe the display of a stripped core gp120 on the yeast cell surface. Validation against a panel of neutralizing antibodies confirms that yeast-displayed gp120 presents the CD4 binding site in the correct conformation. We map the epitope of the broadly neutralizing anti-gp120 antibody VRC01 using both a random mutagenesis library and a defined mutant panel and find that the resultant epitope maps are consistent with one another and with the crystallographically identified contact residues. Mapping the VRC01-competitive antibodies b12 and b13 reveals energetic differences in their epitopes that are not obvious from existing crystal structures. These data suggest mutation sets that abrogate binding to broadly neutralizing antibodies with greater specificity than the canonical mutation D368R, useful in rapidly assessing the nature of a vaccine response. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Mata-Fink, Jordi; Kriegsman, Barry; Yu, Hui Xin; Zhu, Hanna; Wittrup, K. Dane] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Irvine, Darrell J.; Wittrup, K. Dane] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Hanson, Melissa C.; Irvine, Darrell J.] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. [Irvine, Darrell J.; Wittrup, K. Dane] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Irvine, Darrell J.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. [Mata-Fink, Jordi; Irvine, Darrell J.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Boston, MA 02129 USA. RP Wittrup, KD (reprint author), MIT, Dept Chem Engn, MIT 76-261D, Cambridge, MA 02139 USA. EM wittrup@mit.edu OI Hanson, Melissa/0000-0003-3270-8460 FU Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard FX This work was supported by an award from the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard. D.J.I. is an investigator of the Howard Hughes Medical Institute. NR 79 TC 21 Z9 21 U1 0 U2 12 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JAN 23 PY 2013 VL 425 IS 2 BP 444 EP 456 DI 10.1016/j.jmb.2012.11.010 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 095AA UT WOS:000315305700017 PM 23159556 ER PT J AU Chen, ZX Huang, HW Liu, JZ Ng, HKT Nadarajah, S Huang, XD Deng, YP AF Chen, Zhongxue Huang, Hanwen Liu, Jianzhong Ng, Hon Keung Tony Nadarajah, Saralees Huang, Xudong Deng, Youping TI Detecting differentially methylated loci for Illumina Array methylation data based on human ovarian cancer data SO BMC MEDICAL GENOMICS LA English DT Article; Proceedings Paper CT International Conference on Bioinformatics and Computational Biology (BIOCOMP) CY JUL 18-21, 2011 CL Las Vegas, NV ID GENOME-WIDE ASSOCIATION; SINGLE NUCLEOTIDE POLYMORPHISMS; MULTIPLE-TESTING CORRECTION; DNA METHYLATION; GENE AB Background: It is well known that DNA methylation, as an epigenetic factor, has an important effect on gene expression and disease development. Detecting differentially methylated loci under different conditions, such as cancer types or treatments, is of great interest in current research as it is important in cancer diagnosis and classification. However, inappropriate testing approaches can result in large false positives and/or false negatives. Appropriate and powerful statistical methods are desirable but very limited in the literature. Results: In this paper, we propose a nonparametric method to detect differentially methylated loci under multiple conditions for Illumina Array Methylation data. We compare the new method with other methods using simulated and real data. Our study shows that the proposed one outperforms other methods considered in this paper. Conclusions: Due to the unique feature of the Illumina Array Methylation data, commonly used statistical tests will lose power or give misleading results. Therefore, appropriate statistical methods are crucial for this type of data. Powerful statistical approaches remain to be developed. Availability: R codes are available upon request. C1 [Chen, Zhongxue] Indiana Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Bloomington, IN 47405 USA. [Huang, Hanwen] Univ Texas Hlth Sci Ctr Houston, Ctr Clin & Translat Sci, Houston, TX 77030 USA. [Liu, Jianzhong] Chem21 Grp Inc, Lake Forest, IL 60045 USA. [Ng, Hon Keung Tony] So Methodist Univ, Dept Stat Sci, Dallas, TX 75275 USA. [Nadarajah, Saralees] Univ Manchester, Sch Math, Manchester M13 9PL, Lancs, England. [Huang, Xudong] Massachusetts Gen Hosp, Dept Psychiat, Neurochem Lab, Charlestown, MA 02129 USA. [Huang, Xudong] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Deng, Youping] Rush Univ Canc Ctr, Dept Internal Med, Chicago, IL 60612 USA. [Deng, Youping] Rush Univ Med Ctr, Chicago, IL 60612 USA. RP Chen, ZX (reprint author), Indiana Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, 1025 E 7th St, Bloomington, IN 47405 USA. EM zc3@indiana.edu RI Chen, Zhongxue/K-1372-2013 OI Chen, Zhongxue/0000-0003-2537-7843 NR 29 TC 9 Z9 10 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1755-8794 J9 BMC MED GENOMICS JI BMC Med. Genomics PD JAN 23 PY 2013 VL 6 SU 1 AR S9 DI 10.1186/1755-8794-6-S1-S9 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 083OF UT WOS:000314473300009 PM 23369576 ER PT J AU Hu, BQ Jiang, G Pang, CY Wang, SP Liu, QZ Chen, ZX Vanderburg, CR Rogers, JT Deng, YP Huang, XD AF Hu, Benqiong Jiang, Gang Pang, Chaoyang Wang, Shipeng Liu, Qingzhong Chen, Zhongxue Vanderburg, Charles R. Rogers, Jack T. Deng, Youping Huang, Xudong TI Assessment of gene order computing methods for Alzheimer's disease SO BMC MEDICAL GENOMICS LA English DT Article; Proceedings Paper CT International Conference on Bioinformatics and Computational Biology (BIOCOMP) CY JUL 18-21, 2011 CL Las Vegas, NV ID SELF-ORGANIZING MAPS; EXPRESSION PATTERNS; MICROARRAY ANALYSIS; CLUSTER-ANALYSIS; PROTEIN; POLYMORPHISM; ASSOCIATION; MUTATION; NETWORK AB Background: Computational genomics of Alzheimer disease (AD), the most common form of senile dementia, is a nascent field in AD research. The field includes AD gene clustering by computing gene order which generates higher quality gene clustering patterns than most other clustering methods. However, there are few available gene order computing methods such as Genetic Algorithm (GA) and Ant Colony Optimization (ACO). Further, their performance in gene order computation using AD microarray data is not known. We thus set forth to evaluate the performances of current gene order computing methods with different distance formulas, and to identify additional features associated with gene order computation. Methods: Using different distance formulas- Pearson distance and Euclidean distance, the squared Euclidean distance, and other conditions, gene orders were calculated by ACO and GA (including standard GA and improved GA) methods, respectively. The qualities of the gene orders were compared, and new features from the calculated gene orders were identified. Results: Compared to the GA methods tested in this study, ACO fits the AD microarray data the best when calculating gene order. In addition, the following features were revealed: different distance formulas generated a different quality of gene order, and the commonly used Pearson distance was not the best distance formula when used with both GA and ACO methods for AD microarray data. Conclusion: Compared with Pearson distance and Euclidean distance, the squared Euclidean distance generated the best quality gene order computed by GA and ACO methods. C1 [Hu, Benqiong] Chengdu Univ Technol, Coll Management Sci, Chengdu 610059, Peoples R China. [Jiang, Gang; Pang, Chaoyang; Wang, Shipeng] Sichuan Normal Univ, Grp Gene Computat, Coll Math & Software Sci, Chengdu 610066, Peoples R China. [Liu, Qingzhong] Sam Houston State Univ, Dept Comp Sci, Huntsville, TX 77340 USA. [Chen, Zhongxue] Indiana Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Bloomington, IN 47405 USA. [Vanderburg, Charles R.] Massachusetts Gen Hosp, Harvard NeuroDiscovery Ctr, Charlestown, MA 02129 USA. [Vanderburg, Charles R.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Vanderburg, Charles R.; Rogers, Jack T.; Huang, Xudong] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Rogers, Jack T.; Huang, Xudong] Massachusetts Gen Hosp, Dept Psychiat, Neurochem Lab, Charlestown, MA 02129 USA. [Deng, Youping] Rush Univ Canc Ctr, Chicago, IL 60612 USA. [Deng, Youping] Rush Univ Med Ctr, Dept Internal Med, Chicago, IL 60612 USA. RP Huang, XD (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Neurochem Lab, Charlestown, MA 02129 USA. EM xhuang3@partners.org RI Chen, Zhongxue/K-1372-2013 OI Chen, Zhongxue/0000-0003-2537-7843 FU NINDS NIH HHS [R21 NS077079] NR 48 TC 1 Z9 1 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1755-8794 J9 BMC MED GENOMICS JI BMC Med. Genomics PD JAN 23 PY 2013 VL 6 SU 1 AR S8 DI 10.1186/1755-8794-6-S1-S8 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 083OF UT WOS:000314473300008 PM 23369541 ER PT J AU El-Far, M Isabelle, C Chomont, N Bourbonniere, M Fonseca, S Ancuta, P Peretz, Y Chouikh, Y Halwani, R Schwartz, O Madrenas, J Freeman, GJ Routy, JP Haddad, EK Sekaly, RP AF El-Far, Mohamed Isabelle, Catherine Chomont, Nicolas Bourbonniere, Martin Fonseca, Simone Ancuta, Petronela Peretz, Yoav Chouikh, Younes Halwani, Rabih Schwartz, Olivier Madrenas, Joaquin Freeman, Gordon J. Routy, Jean-Pierre Haddad, Elias K. Sekaly, Rafick-Pierre TI Down-Regulation of CTLA-4 by HIV-1 Nef Protein SO PLOS ONE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CD4(+) T-CELLS; LYMPHOCYTE-ASSOCIATED MOLECULE-4; SURFACE CD4; BETA-COP; PHYSICAL INTERACTION; CYTOPLASMIC DOMAIN; DILEUCINE MOTIF; ADAPTER PROTEIN; UP-REGULATION AB HIV-1 Nef protein down-regulates several cell surface receptors through its interference with the cell sorting and trafficking machinery. Here we demonstrate for the first time the ability of Nef to down-regulate cell surface expression of the negative immune modulator CTLA-4. Down-regulation of CTLA-4 required the Nef motifs DD175, EE155 and LL165, all known to be involved in vesicle trafficking. Disruption of the lysosomal functions by pH-neutralizing agents prevented CTLA-4 down-regulation by Nef, demonstrating the implication of the endosomal/lysosomal compartments in this process. Confocal microscopy experiments visualized the co-localization between Nef and CTLA-4 in the early and recycling endosomes but not at the cell surface. Overall, our results provide a novel mechanism by which HIV-1 Nef interferes with the surface expression of the negative regulator of T cell activation CTLA-4. Down-regulation of CTLA-4 may contribute to the mechanisms by which HIV-1 sustains T cell activation, a critical step in viral replication and dissemination. C1 [El-Far, Mohamed; Isabelle, Catherine; Chomont, Nicolas; Bourbonniere, Martin; Fonseca, Simone; Ancuta, Petronela; Peretz, Yoav; Chouikh, Younes; Haddad, Elias K.; Sekaly, Rafick-Pierre] Hop St Luc, CRCHUM, Montreal, PQ H2X 1P1, Canada. [El-Far, Mohamed; Isabelle, Catherine; Chomont, Nicolas; Bourbonniere, Martin; Fonseca, Simone; Peretz, Yoav; Chouikh, Younes; Haddad, Elias K.; Sekaly, Rafick-Pierre] Univ Montreal, Dept Microbiol & Immunol, Immunol Lab, Montreal, PQ H3C 3J7, Canada. [Chomont, Nicolas; Fonseca, Simone; Haddad, Elias K.; Sekaly, Rafick-Pierre] Vaccine & Gene Therapy Inst Florida, Port St Lucie, FL USA. [Halwani, Rabih] King Saud Univ, Coll Med, Prince Naif Ctr Immunol Res, Riyadh 11461, Saudi Arabia. [Halwani, Rabih] King Saud Univ, Coll Med, Dept Pediat, Riyadh 11461, Saudi Arabia. [Schwartz, Olivier] Inst Pasteur, Dept Virol, Virus & Immun Grp, Paris, France. [Madrenas, Joaquin] McGill Univ, Dept Microbiol & Immunol, Montreal, PQ, Canada. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Routy, Jean-Pierre] McGill Univ, Royal Victoria Hosp, Ctr Hlth, Chron Viral Illness Serv, Montreal, PQ H3A 1A1, Canada. [Routy, Jean-Pierre] McGill Univ, Royal Victoria Hosp, Div Hematol, Ctr Hlth, Montreal, PQ H3A 1A1, Canada. RP Sekaly, RP (reprint author), Hop St Luc, CRCHUM, 264 Rene Levesque Blvd E, Montreal, PQ H2X 1P1, Canada. EM rpsekaly@vgtifl.org FU Canadian Institute of Health Research (CIHR); Fonds de la recherche en sante du Quebec (FRSQ); US National Institutes of Health (NIH); Canadian Foundation for AIDS Research; Fonds de la recherche en sante du Quebec AIDS and Infectious Disease Network (SIDA-MI); Canadian Network for Vaccines and Immunotherapeutics FX M.E. and R.H. are funded by the Canadian Institute of Health Research (CIHR). J-P.R. is clinician scientist supported by Fonds de la recherche en sante du Quebec (FRSQ). This study was supported by funds from the US National Institutes of Health (NIH), the Canadian Institute of Health Research (CIHR), the Canadian Foundation for AIDS Research, the Fonds de la recherche en sante du Quebec AIDS and Infectious Disease Network (SIDA-MI) and the Canadian Network for Vaccines and Immunotherapeutics. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 63 TC 6 Z9 8 U1 1 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 23 PY 2013 VL 8 IS 1 AR e54295 DI 10.1371/journal.pone.0054295 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 077IQ UT WOS:000314021500053 PM 23372701 ER PT J AU Liu, LB Chu, KK Houser, GH Diephuis, BJ Li, Y Wilsterman, EJ Shastry, S Dierksen, G Birket, SE Mazur, M Byan-Parker, S Grizzle, WE Sorscher, EJ Rowe, SM Tearney, GJ AF Liu, Linbo Chu, Kengyeh K. Houser, Grace H. Diephuis, Bradford J. Li, Yao Wilsterman, Eric J. Shastry, Suresh Dierksen, Gregory Birket, Susan E. Mazur, Marina Byan-Parker, Suzanne Grizzle, William E. Sorscher, Eric J. Rowe, Steven M. Tearney, Guillermo J. TI Method for Quantitative Study of Airway Functional Microanatomy Using Micro-Optical Coherence Tomography SO PLOS ONE LA English DT Article ID CILIARY BEAT FREQUENCY; VASOACTIVE-INTESTINAL-PEPTIDE; CYSTIC-FIBROSIS GENE; MUCOCILIARY TRANSPORT; TRACHEAL EPITHELIUM; PERICILIARY LIQUID; IN-VITRO; MUCUS; SECRETION; CLEARANCE AB We demonstrate the use of a high resolution form of optical coherence tomography, termed micro-OCT (mu OCT), for investigating the functional microanatomy of airway epithelia. mu OCT captures several key parameters governing the function of the airway surface (airway surface liquid depth, periciliary liquid depth, ciliary function including beat frequency, and mucociliary transport rate) from the same series of images and without exogenous particles or labels, enabling non-invasive study of dynamic phenomena. Additionally, the high resolution of mu OCT reveals distinguishable phases of the ciliary stroke pattern and glandular extrusion. Images and functional measurements from primary human bronchial epithelial cell cultures and excised tissue are presented and compared with measurements using existing gold standard methods. Active secretion from mucus glands in tissue, a key parameter of epithelial function, was also observed and quantified. C1 [Liu, Linbo; Chu, Kengyeh K.; Diephuis, Bradford J.; Wilsterman, Eric J.; Dierksen, Gregory; Tearney, Guillermo J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Liu, Linbo; Chu, Kengyeh K.; Wilsterman, Eric J.; Dierksen, Gregory] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Houser, Grace H.] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA. [Diephuis, Bradford J.; Tearney, Guillermo J.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. [Diephuis, Bradford J.] Harvard Univ, Sch Med, Boston, MA USA. [Li, Yao; Shastry, Suresh; Mazur, Marina; Sorscher, Eric J.; Rowe, Steven M.] Univ Alabama Birmingham, Cyst Fibrosis Res Ctr, Birmingham, AL USA. [Birket, Susan E.; Sorscher, Eric J.; Rowe, Steven M.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Byan-Parker, Suzanne; Grizzle, William E.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Tearney, Guillermo J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Rowe, SM (reprint author), Univ Alabama Birmingham, Cyst Fibrosis Res Ctr, Birmingham, AL USA. EM smrowe@uab.edu; gtearney@partners.org FU US National Institute of Health [P30 DK072482, R01 HL105487, R01 HL076398]; Cystic Fibrosis Foundation [R464-CF, SORSCH05XX0, ROWE10XX0, CLANCY09Y2, TEARNE07XX0]; Massachusetts General Hospital ECOR Postdoctoral fellowship [2011A052538] FX This research was supported by US National Institute of Health (http://www.nih.gov/; Contracts P30 DK072482 to EJS, R01 HL105487 to SMR, and R01 HL076398 to GJT), Cystic Fibrosis Foundation (http://www.cff.org/; Contracts R464-CF and SORSCH05XX0 to EJS, ROWE10XX0 and CLANCY09Y2 to SMR, and TEARNE07XX0 to GJT), and Massachusetts General Hospital ECOR Postdoctoral fellowship (http://www.massgeneral.org/; Award 2011A052538). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 44 TC 21 Z9 21 U1 1 U2 27 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 23 PY 2013 VL 8 IS 1 AR e54473 DI 10.1371/journal.pone.0054473 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 077IQ UT WOS:000314021500077 PM 23372732 ER PT J AU Lim, ET Raychaudhuri, S Sanders, SJ Stevens, C Sabo, A MacArthur, DG Neale, BM Kirby, A Ruderfer, DM Fromer, M Lek, M Liu, L Flannick, J Ripke, S Nagaswamy, U Muzny, D Reid, JG Hawes, A Newsham, I Wu, YQ Lewis, L Dinh, H Gross, S Wang, LS Lin, CF Valladares, O Gabriel, SB dePristo, M Altshuler, DM Purcell, SM State, MW Boerwinkle, E Buxbaum, JD Cook, EH Gibbs, RA Schellenberg, GD Sutcliffe, JS Devlin, B Roeder, K Daly, MJ AF Lim, Elaine T. Raychaudhuri, Soumya Sanders, Stephan J. Stevens, Christine Sabo, Aniko MacArthur, Daniel G. Neale, Benjamin M. Kirby, Andrew Ruderfer, Douglas M. Fromer, Menachem Lek, Monkol Liu, Li Flannick, Jason Ripke, Stephan Nagaswamy, Uma Muzny, Donna Reid, Jeffrey G. Hawes, Alicia Newsham, Irene Wu, Yuanqing Lewis, Lora Dinh, Huyen Gross, Shannon Wang, Li-San Lin, Chiao-Feng Valladares, Otto Gabriel, Stacey B. dePristo, Mark Altshuler, David M. Purcell, Shaun M. State, Matthew W. Boerwinkle, Eric Buxbaum, Joseph D. Cook, Edwin H. Gibbs, Richard A. Schellenberg, Gerard D. Sutcliffe, James S. Devlin, Bernie Roeder, Kathryn Daly, Mark J. CA NHLBI Exome Sequencing Project TI Rare Complete Knockouts in Humans: Population Distribution and Significant Role in Autism Spectrum Disorders SO NEURON LA English DT Article ID COPY-NUMBER VARIATION; DE-NOVO MUTATIONS; CANDIDATE GENES; SEQUENCING DATA; VARIANTS; GENOME; EXOME; ASSOCIATION; FAMILIES; BRAIN AB To characterize the role of rare complete human knockouts in autism spectrum disorders (ASDs), we identify genes with homozygous or compound heterozygous loss-of-function (LoF) variants (defined as nonsense and essential splice sites) from exome sequencing of 933 cases and 869 controls. We identify a 2-fold increase in complete knockouts of autosomal genes with low rates of LoF variation (<= 5% frequency) in cases and estimate a 3% contribution to ASD risk by these events, confirming this observation in an independent set of 563 probands and 4,605 controls. Outside the pseudoautosomal regions on the X chromosome, we similarly observe a significant 1.5-fold increase in rare hemizygous knockouts in males, contributing to another 2% of ASDs in males. Taken together, these results provide compelling evidence that rare autosomal and X chromosome complete gene knockouts are important inherited risk factors for ASD. C1 [Lim, Elaine T.; MacArthur, Daniel G.; Neale, Benjamin M.; Kirby, Andrew; Ruderfer, Douglas M.; Fromer, Menachem; Lek, Monkol; Flannick, Jason; Ripke, Stephan; Altshuler, David M.; Purcell, Shaun M.; Daly, Mark J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Flannick, Jason; Altshuler, David M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Ruderfer, Douglas M.; Fromer, Menachem; Purcell, Shaun M.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Lim, Elaine T.; Raychaudhuri, Soumya; Stevens, Christine; MacArthur, Daniel G.; Neale, Benjamin M.; Kirby, Andrew; Ruderfer, Douglas M.; Fromer, Menachem; Lek, Monkol; Flannick, Jason; Ripke, Stephan; Gabriel, Stacey B.; dePristo, Mark; Altshuler, David M.; Purcell, Shaun M.; Daly, Mark J.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Lim, Elaine T.; Neale, Benjamin M.; Ruderfer, Douglas M.; Fromer, Menachem; Ripke, Stephan; Purcell, Shaun M.; Daly, Mark J.] Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Lim, Elaine T.; Raychaudhuri, Soumya; MacArthur, Daniel G.; Neale, Benjamin M.; Kirby, Andrew; Ruderfer, Douglas M.; Fromer, Menachem; Lek, Monkol; Flannick, Jason; Altshuler, David M.; Purcell, Shaun M.; Daly, Mark J.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Lim, Elaine T.; Raychaudhuri, Soumya; MacArthur, Daniel G.; Neale, Benjamin M.; Kirby, Andrew; Ruderfer, Douglas M.; Fromer, Menachem; Lek, Monkol; Flannick, Jason; Altshuler, David M.; Purcell, Shaun M.; Daly, Mark J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Lim, Elaine T.] Harvard Univ, Sch Med, Program Genet & Genom Biol & Biomed Sci, Boston, MA 02115 USA. [Ruderfer, Douglas M.; Fromer, Menachem; Purcell, Shaun M.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Raychaudhuri, Soumya] Brigham & Womens Hosp, Div Immunol Allergy & Rheumatol, Boston, MA 02115 USA. [Sanders, Stephan J.; State, Matthew W.] Yale Univ, Dept Psychiat, Sch Med, New Haven, CT 06520 USA. [Sanders, Stephan J.; State, Matthew W.] Yale Univ, Dept Genet, Sch Med, New Haven, CT 06520 USA. [Sabo, Aniko; Nagaswamy, Uma; Muzny, Donna; Reid, Jeffrey G.; Hawes, Alicia; Newsham, Irene; Wu, Yuanqing; Lewis, Lora; Dinh, Huyen; Gross, Shannon; Boerwinkle, Eric; Gibbs, Richard A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Ruderfer, Douglas M.; Fromer, Menachem; Purcell, Shaun M.] Mt Sinai Sch Med, Div Psychiat Genom, New York, NY 10029 USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Seaver Autism Ctr Res & Treatment, New York, NY 10029 USA. [Ruderfer, Douglas M.; Fromer, Menachem; Purcell, Shaun M.; Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Ruderfer, Douglas M.; Fromer, Menachem; Purcell, Shaun M.; Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. [Buxbaum, Joseph D.] Mt Sinai Sch Med, Friedman Brain Inst, New York, NY 10029 USA. [Liu, Li; Roeder, Kathryn] Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. [Liu, Li; Roeder, Kathryn] Carnegie Mellon Univ, Lane Ctr Computat Biol, Pittsburgh, PA 15213 USA. [Wang, Li-San; Lin, Chiao-Feng; Valladares, Otto] Univ Penn, Penn Ctr Bioinformat, Philadelphia, PA 19104 USA. [Schellenberg, Gerard D.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX 77030 USA. [Cook, Edwin H.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. [Sutcliffe, James S.] Vanderbilt Univ, Vanderbilt Brain Inst, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. [Sutcliffe, James S.] Vanderbilt Univ, Vanderbilt Brain Inst, Dept Psychiat, Nashville, TN 37232 USA. [Devlin, Bernie] Univ Pittsburgh, Dept Psychiat, Sch Med, Pittsburgh, PA 15260 USA. RP Daly, MJ (reprint author), Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. EM mjdaly@atgu.mgh.harvard.edu RI Altshuler, David/A-4476-2009; Sutcliffe, James/C-1348-2012; Liu, Li/G-1897-2015; Ruderfer, Douglas/M-5795-2016; Fromer, Menachem/G-2116-2012; OI Altshuler, David/0000-0002-7250-4107; Sutcliffe, James/0000-0001-5200-6007; Ruderfer, Douglas/0000-0002-2365-386X; Fromer, Menachem/0000-0003-3749-4342; Buxbaum, Joseph/0000-0001-8898-8313; Sanders, Stephan/0000-0001-9112-5148 FU National Institute of Mental Health (NIMH) repository [U24MH068457]; Autism Genetic Resource Exchange (AGRE) Consortium [1U24MH081810]; Autism Speaks; Simons Foundation; Autism Consortium; NIH [R01MH089208, R01MH089025, R01MH089004, R01MH089175, R01MH089482, P50HD055751, R01MH057881, R01MH061009]; Lung GO Sequencing Project [HL-102923]; WHI Sequencing Project [HL-102924]; Broad GO Sequencing Project [HL-102925]; Seattle GO Sequencing Project [HL-102926]; Heart GO Sequencing Project [HL-103010]; [U54 HG003273]; [U54 HG003067] FX We gratefully acknowledge the following resources and families who contributed to them: the National Institute of Mental Health (NIMH) repository (U24MH068457); Autism Genetic Resource Exchange (AGRE) Consortium, a program of Autism Speaks (1U24MH081810 to Clara M. Lajonchere); The Autism Simplex Collection (TASC) (grant from Autism Speaks); Simons Foundation Autism Research Initiative (SFARI) Simplex Collection (grant from the Simons Foundation); The Autism Consortium (grant from the Autism Consortium). For full citation of resources, please see Supplemental Information. This work was directly supported by NIH grants R01MH089208 (M.J.D.), R01MH089025 (J.D.B.), R01MH089004 (G.D.S.), R01MH089175 (R.A.G.), and R01MH089482 (J.S.S.) and supported in part by NIH grants P50HD055751 (E.H.C.), R01MH057881 (S.D.), and R01MH061009 (J.S.S.). We acknowledge partial support from U54 HG003273 (R.A.G.) and U54 HG003067 (E. Lander). We thank Thomas Lehner (NIMH), Adam Felsenfeld (NHGRI), and Patrick Bender (NIMH) for their support and contribution to the project. E.B., J.D.B., S.D., M.J.D., R.A.G., K.R., A.S., G.D.S., and J.S.S. are lead investigators in the ARRA Autism Sequencing Collaboration (AASC). We would also like to thank the NHLBI GO Exome Sequencing Project and its ongoing studies that produced and provided exome variant calls for comparison: the Lung GO Sequencing Project (HL-102923), the WHI Sequencing Project (HL-102924), the Broad GO Sequencing Project (HL-102925), the Seattle GO Sequencing Project (HL-102926), and the Heart GO Sequencing Project (HL-103010). NR 42 TC 107 Z9 112 U1 1 U2 28 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD JAN 23 PY 2013 VL 77 IS 2 BP 235 EP 242 DI 10.1016/j.neuron.2012.12.029 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 079VD UT WOS:000314199400006 PM 23352160 ER PT J AU Yu, TW Chahrour, MH Coulter, ME Jiralerspong, S Okamura-Ikeda, K Ataman, B Schmitz-Abe, K Harmin, DA Adli, M Malik, AN D'Gama, AM Lim, ET Sanders, SJ Mochida, GH Partlow, JN Sunu, CM Felie, JM Rodriguez, J Nasir, RH Ware, J Joseph, RM Hill, RS Kwan, BY Al-Saffar, M Mukaddes, NM Hashmi, A Balkhy, S Gascon, GG Hisama, FM LeClair, E Poduri, A Oner, O Al-Saad, S Al-Awadi, SA Bastaki, L Ben-Omran, T Teebi, AS Al-Gazali, L Eapen, V Stevens, CR Rappaport, L Gabriel, SB Markianos, K State, MW Greenberg, ME Taniguchi, H Braverman, NE Morrow, EM Walsh, CA AF Yu, Timothy W. Chahrour, Maria H. Coulter, Michael E. Jiralerspong, Sarn Okamura-Ikeda, Kazuko Ataman, Bulent Schmitz-Abe, Klaus Harmin, David A. Adli, Mazhar Malik, Athar N. D'Gama, Alissa M. Lim, Elaine T. Sanders, Stephan J. Mochida, Ganesh H. Partlow, Jennifer N. Sunu, Christine M. Felie, Jillian M. Rodriguez, Jacqueline Nasir, Ramzi H. Ware, Janice Joseph, Robert M. Hill, R. Sean Kwan, Benjamin Y. Al-Saffar, Muna Mukaddes, Nahit M. Hashmi, Asif Balkhy, Soher Gascon, Generoso G. Hisama, Fuki M. LeClair, Elaine Poduri, Annapurna Oner, Ozgur Al-Saad, Samira Al-Awadi, Sadika A. Bastaki, Laila Ben-Omran, Tawfeg Teebi, Ahmad S. Al-Gazali, Lihadh Eapen, Valsamma Stevens, Christine R. Rappaport, Leonard Gabriel, Stacey B. Markianos, Kyriacos State, Matthew W. Greenberg, Michael E. Taniguchi, Hisaaki Braverman, Nancy E. Morrow, Eric M. Walsh, Christopher A. TI Using Whole-Exome Sequencing to Identify Inherited Causes of Autism SO NEURON LA English DT Article ID RHIZOMELIC CHONDRODYSPLASIA PUNCTATA; DE-NOVO MUTATIONS; GLYCINE CLEAVAGE SYSTEM; COPY-NUMBER VARIATION; COHEN-SYNDROME; SPECTRUM DISORDERS; NONKETOTIC HYPERGLYCINEMIA; CLINICAL VARIABILITY; CRYSTAL-STRUCTURE; PTS2 RECEPTOR AB Despite significant heritability of autism spectrum disorders (ASDs), their extreme genetic heterogeneity has proven challenging for gene discovery. Studies of primarily simplex families have implicated de novo copy number changes and point mutations, but are not optimally designed to identify inherited risk alleles. We apply whole-exome sequencing (WES) to ASD families enriched for inherited causes due to consanguinity and find familial ASD associated with biallelic mutations in disease genes (AMT, PEX7, SYNE1, VPS13B, PAH, and POMGNT1). At least some of these genes show biallelic mutations in nonconsanguineous families as well. These mutations are often only partially disabling or present atypically, with patients lacking diagnostic features of the Mendelian disorders with which these genes are classically associated. Our study shows the utility of WES for identifying specific genetic conditions not clinically suspected and the importance of partial loss of gene function in ASDs. C1 [Yu, Timothy W.; Chahrour, Maria H.; Coulter, Michael E.; Schmitz-Abe, Klaus; Mochida, Ganesh H.; Partlow, Jennifer N.; Sunu, Christine M.; Felie, Jillian M.; Rodriguez, Jacqueline; Hill, R. Sean; Al-Saffar, Muna; Markianos, Kyriacos; Walsh, Christopher A.] Boston Childrens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. [Yu, Timothy W.; Chahrour, Maria H.; Coulter, Michael E.; Schmitz-Abe, Klaus; Mochida, Ganesh H.; Partlow, Jennifer N.; Sunu, Christine M.; Felie, Jillian M.; Rodriguez, Jacqueline; Hill, R. Sean; Al-Saffar, Muna; Markianos, Kyriacos; Walsh, Christopher A.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Boston, MA 02115 USA. [Yu, Timothy W.; Chahrour, Maria H.; Coulter, Michael E.; Mochida, Ganesh H.; Partlow, Jennifer N.; Sunu, Christine M.; Felie, Jillian M.; Rodriguez, Jacqueline; Hill, R. Sean; Walsh, Christopher A.] Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Yu, Timothy W.; Chahrour, Maria H.; Joseph, Robert M.; Rappaport, Leonard; Morrow, Eric M.; Walsh, Christopher A.] Autism Consortium, Boston, MA 02115 USA. [Yu, Timothy W.; Chahrour, Maria H.; Coulter, Michael E.; Schmitz-Abe, Klaus; D'Gama, Alissa M.; Mochida, Ganesh H.; Nasir, Ramzi H.; Ware, Janice; Hill, R. Sean; LeClair, Elaine; Poduri, Annapurna; Rappaport, Leonard; Markianos, Kyriacos; Walsh, Christopher A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Yu, Timothy W.; Mochida, Ganesh H.; Gascon, Generoso G.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Yu, Timothy W.; Chahrour, Maria H.; Stevens, Christine R.; Gabriel, Stacey B.; Walsh, Christopher A.] MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Yu, Timothy W.; Chahrour, Maria H.; Stevens, Christine R.; Gabriel, Stacey B.; Walsh, Christopher A.] Harvard Univ, Cambridge, MA 02142 USA. [Jiralerspong, Sarn; Braverman, Nancy E.] McGill Univ, Montreal Childrens Hosp, Res Inst, Dept Human Genet & Pediat, Montreal, PQ H3H 1P3, Canada. [Okamura-Ikeda, Kazuko; Taniguchi, Hisaaki] Univ Tokushima, Inst Enzyme Res, Tokushima 7708501, Japan. [Ataman, Bulent; Harmin, David A.; Malik, Athar N.; Greenberg, Michael E.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Adli, Mazhar] Univ Virginia, Sch Med, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA. [Lim, Elaine T.] Massachusetts Gen Hosp, Ctr Human Genet Res, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Sanders, Stephan J.; State, Matthew W.] Yale Univ, Sch Med, Dept Genet, Ctr Human Genet & Genom, New Haven, CT 06510 USA. [Sanders, Stephan J.; State, Matthew W.] Yale Univ, Sch Med, Program Neurogenet, New Haven, CT 06510 USA. [Nasir, Ramzi H.; Ware, Janice; LeClair, Elaine; Rappaport, Leonard] Boston Childrens Hosp, Div Dev Med, Boston, MA 02115 USA. [Joseph, Robert M.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Kwan, Benjamin Y.] Univ Western Ontario, Schulich Sch Med & Dent, London, ON N6A 5C1, Canada. [Al-Saffar, Muna; Al-Gazali, Lihadh] United Arab Emirates Univ, Fac Med & Hlth Sci, Dept Paediat, Al Ain, U Arab Emirates. [Mukaddes, Nahit M.; Gascon, Generoso G.] Istanbul Univ, Dept Child Psychiat, Istanbul Fac Med, TR-34452 Istanbul, Turkey. [Hashmi, Asif] Armed Forces Hosp, King Abdulaziz Naval Base, Jubail Ind City 31951, Saudi Arabia. [Balkhy, Soher] King Faisal Specialist Hosp & Res Ctr, Dept Neurosci & Pediat, Jeddah 21499, Saudi Arabia. [Gascon, Generoso G.] Brown Univ, Sch Med, Providence, RI 02912 USA. [Hisama, Fuki M.] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. [Poduri, Annapurna] Boston Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Oner, Ozgur] Dr Sami Ulus Childrens Hosp, Dept Child & Adolescent Psychiat, TR-06090 Ankara, Turkey. [Al-Saad, Samira] Kuwait Ctr Autism, Kuwait 73455, Kuwait. [Al-Awadi, Sadika A.; Bastaki, Laila] Kuwait Med Genet Ctr, Kuwait 72458, Kuwait. [Ben-Omran, Tawfeg; Teebi, Ahmad S.] Hamad Med Corp, Dept Pediat, Sect Clin & Metab Genet, Doha, Qatar. [Ben-Omran, Tawfeg; Teebi, Ahmad S.] Weill Cornell Med Coll, Dept Pediat, New York, NY 10065 USA. [Ben-Omran, Tawfeg; Teebi, Ahmad S.] Weill Cornell Med Coll, Dept Med Genet, New York, NY 10065 USA. [Ben-Omran, Tawfeg; Teebi, Ahmad S.] Weill Cornell Med Coll, Dept Pediat, Doha, Qatar. [Ben-Omran, Tawfeg; Teebi, Ahmad S.] Weill Cornell Med Coll, Dept Med Genet, Doha, Qatar. [Eapen, Valsamma] Univ New S Wales, Acad Unit Child Psychiat SW Sydney AUCS, Sydney, NSW 2170, Australia. [Morrow, Eric M.] Brown Univ, Dept Mol Biol Cell Biol & Biochem, Providence, RI 02912 USA. [Morrow, Eric M.] Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA. RP Yu, TW (reprint author), Boston Childrens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. EM timothy.yu@childrens.harvard.edu; christopher.walsh@childrens.harvard.edu RI Morrow, Eric/J-2767-2013; OI Chahrour, Maria/0000-0002-3174-1480; Sanders, Stephan/0000-0001-9112-5148; Yu, Timothy/0000-0003-2988-7701 FU National Institute of Mental Health (NIMH); National Institute of Health (NIH) [T32 NS007484-08, T32 N5007473-12]; Clinical Investigator Training Program (CITP) at Harvard-MIT Health Sciences and Technology; Beth Israel Deaconess Medical Center; Pfizer, Inc.; Merck and Company, Inc.; Nancy Lurie Marks Junior Faculty MeRIT Fellowship; NARSAD; National Institutes of Neurological Disease and Stroke [K23NS069784]; National Institute of General Medical Sciences [T32GM07753]; National Institute of Mental Health [RO1 MH083565, 1RC2MH089952]; NIH [RO1 N5048276]; NIMH [1K23MH080954-01]; Dubai Harvard Foundation for Medical Research; Nancy Lurie Marks Foundation; Simons Foundation; Autism Consortium; Manton Center for Orphan Disease Research; ARRA Grand Opportunities [1RC2MH089952] FX We are grateful to Ed Gilmore, Chiara Manzini, Jenny Yang, and Mark Daly for stimulating discussions and helpful comments on the manuscript and Thomas Lehner for support from the National Institute of Mental Health (NIMH). We are also grateful for the participation of the many families that enrolled in our studies as well as for the collaborative support of the Kuwait Center for Autism and the Dubai Autism Center. T.W.Y. was supported by a National Institute of Health (NIH) T32 grant (T32 NS007484-08), the Clinical Investigator Training Program (CITP) at Harvard-MIT Health Sciences and Technology and Beth Israel Deaconess Medical Center in collaboration with Pfizer, Inc. and Merck and Company, Inc., and the Nancy Lurie Marks Junior Faculty MeRIT Fellowship. M.H.C. was supported by a NIH T32 grant (T32 N5007473-12). G.H.M. was supported by the Young Investigator Award of NARSAD as a NARSAD Lieber Investigator. A.P. was supported by the National Institutes of Neurological Disease and Stroke (K23NS069784). A.M.D. was supported by the National Institute of General Medical Sciences (T32GM07753). Research was supported by grants from the National Institute of Mental Health (RO1 MH083565; 1RC2MH089952) to C.A.W., the NIH to M.E.G. (RO1 N5048276), the NIMH to E.M.M. (1K23MH080954-01), the Dubai Harvard Foundation for Medical Research, the Nancy Lurie Marks Foundation, the Simons Foundation, the Autism Consortium, and the Manton Center for Orphan Disease Research. Sequencing at the Broad Institute was supported by the ARRA Grand Opportunities grant 1RC2MH089952. C.A.W. is an Investigator of the Howard Hughes Medical Institute. T.W.Y. identified AMT, PEX7, and SYNE1 mutations, helped design AMT and PEX7 functional studies, designed and performed exome sequencing analyses for candidate genes, contributed to CNV analyses, and wrote the manuscript. M.H.C. designed and performed exome sequencing analyses for candidate genes, analyzed Sanger validation data and SSC exome data, and wrote the manuscript. M.E.C. helped analyze AU-1700 and AU-3500. S.J. designed PEX7 functional experiments with N.E.B., and S.J. performed them. K.O.-I. designed and performed AMT functional studies and analyzed results. B.A. designed and analyzed RNAseq, ChIPseq, and gPOR experiments. D.A.H. analyzed RNAseq and qPCR experiments. M.A. performed ChIPseq experiments, and A.N.M. analyzed the data. A.M.D. performed RACE experiments for SYNE1. K.S.-A. and K.M. designed the CNV analysis, and KS.-A. compiled the CNV catalog and identified pathogenic CNVs. E.T.L. and S.J.S. helped analyze SSC whole-exome data. G.H.M. performed clinical phenotyping of Middle Eastern families as well as detailed molecular analyses of AU-8600. J.N.P. organized clinical information and patient samples. C.M.S. assisted with exome sequencing analyses and performed follow-up Sanger validation. J.M.F. and J.R. performed follow-up Sanger validation. R.H.N. performed clinical phenotyping of AU-17800. J.W performed clinical phenotyping of AU-17700 and AU-17800. R.M.J. performed clinical phenotyping of AU-1600, AU-10000, and AU-10200. R.S.H. performed genome-wide linkage studies and homozygosity analyses. B.Y.K. assisted with characterization of the AMT mutation. MA-S. organized clinical information and patient samples and referred AU17700 and AU-17800. N.M.M. referred and clinically characterized AU-4200, AU-4400, AU-4900, AU-5700, AU-6100, AU-6200, AU-6300, AU-8600, AU11100, AU-11800, AU-11900, AU-12100, AU-12400, AU-14900, AU-15800, AU-16700, AU-20700, AU-22500, AU-23400, and AU-24300. A.H.; referred and characterized AU-3500 and AU-3600. S.B. referred and characterized AU-1700. G.G. referred and characterized AU-1700, AU-3100, AU-4100, and AU-6000. F.M.H. helped characterize AU-17700 and AU-17800. E.L. and A.P. performed clinical phenotyping of AU-1600, AU-10000, and AU10200. 0.0. referred and characterized AU-13100, AU-13400, AU-18000, AU-20300, and AU-22000. S.A.-S., S.A.A.-A., and LB. referred and characterized AU-1600. S.A.-S. referred and characterized AU-9600. T.B.-0. and A.S.T. referred and characterized AU-21100. L.A.-G. and V.E. referred and characterized AU-3200. C.R.S. organized and coordinated exome sequencing. L.R. evaluated the second compound heterozygous PEX7 family. S.B.G. directed exome sequencing. KM. designed the CNV analysis. M.W.S. oversaw SSC exome analyses. M.E.G. oversaw SYNE1 RNAseq and qPCR experiments. H.T. designed and performed AMT functional experiments. N.E.B. designed PEX7 functional experiments, recruited the nonconsanguineous family with two sisters affected by PEX7 mutation, and contributed to interpretation of PEX7 sequencing data. E.M.M. helped characterize AU-1700, performed linkage studies on AU-1600, AU-1700, and AU-3500, helped design the exome sequencing experiment, and contributed to finding the SYNE1 mutation. C.A.W. directed the overall research and wrote the manuscript. NR 70 TC 154 Z9 159 U1 3 U2 71 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD JAN 23 PY 2013 VL 77 IS 2 BP 259 EP 273 DI 10.1016/j.neuron.2012.11.002 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 079VD UT WOS:000314199400009 PM 23352163 ER PT J AU Vaduganathan, M Bonow, RO Gheorghiade, M AF Vaduganathan, Muthiah Bonow, Robert O. Gheorghiade, Mihai TI Thirty-Day Readmissions The Clock Is Ticking SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID HEART-FAILURE C1 [Vaduganathan, Muthiah] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Bonow, Robert O.; Gheorghiade, Mihai] Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Dept Med, Chicago, IL 60611 USA. RP Gheorghiade, M (reprint author), Northwestern Univ, Feinberg Sch Med, Ctr Cardiovasc Innovat, Dept Med, 645 N Michigan Ave,Ste 1006, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu NR 8 TC 57 Z9 57 U1 0 U2 9 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 23 PY 2013 VL 309 IS 4 BP 345 EP 346 DI 10.1001/jama.2012.205110 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 074FT UT WOS:000313799000018 PM 23340632 ER PT J AU McCoy, JG Christie, MA Kim, Y Brennan, R Poeta, DL McCarley, RW Strecker, RE AF McCoy, John G. Christie, Michael A. Kim, Youngsoo Brennan, Robert Poeta, Devon L. McCarley, Robert W. Strecker, Robert E. TI Chronic sleep restriction impairs spatial memory in rats SO NEUROREPORT LA English DT Article DE animal model; behavior; cognition; hippocampus; learning; memory; sleep; sleep deprivation; sleep loss; water maze ID ADOLESCENT RATS; RISK-FACTOR; NEUROGENESIS; DEPRIVATION; WAKEFULNESS; HOMEOSTASIS; ADENOSINE; DURATION; COST AB Although numerous experimental investigations have evaluated the neurobehavioral effects of either short periods of total sleep deprivation or selective rapid eye movement sleep deprivation, few studies have examined the effects of chronic sleep restriction (CSR). Long-Evans rats were deprived of sleep by the automated movement of activity wheels for 18 h/day for 5 consecutive days from 16: 00 to 10: 00 h, and were allowed 6 h/day of sleep opportunity (10:00-16:00 h; lights on from 10: 00 to 22: 00 h). Activity wheels were intermittently activated on a 3 s on : 12 s off schedule for the CSR condition, whereas a schedule of 36 min of continuous wheel movement in every 3 h was used for a cage movement control condition. A cross-over design was used with rats serving in both the CSR and the movement control conditions with 2 days of rest between conditions. Water maze acquisition training occurred at 16: 00 h immediately after the 6-h sleep opportunity on each of the first 4 days, followed by a probe trial on day 5 to assess spatial memory recall. Although the rate of learning/acquisition was not affected by the daily 18 h of CSR, the day 5 recall of the platform location was impaired on three different probe trial measures. Thus, CSR impaired spatial memory, but did not affect the rate of learning/acquisition in the water maze. NeuroReport 24:91-95 (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. NeuroReport 2013, 24:91-95 C1 [McCoy, John G.; Christie, Michael A.; Kim, Youngsoo; McCarley, Robert W.; Strecker, Robert E.] VA Boston Healthcare Syst, Res Serv, Brockton, MA 02301 USA. [McCoy, John G.; Christie, Michael A.; Kim, Youngsoo; McCarley, Robert W.; Strecker, Robert E.] Harvard Univ, Sch Med, Dept Psychiat, Brockton, MA 02301 USA. [McCoy, John G.; Brennan, Robert; Poeta, Devon L.; Strecker, Robert E.] Stonehill Coll, Dept Psychol, Easton, MA USA. RP Strecker, RE (reprint author), VA Boston Healthcare Syst, Res Serv, 940 Belmont St,151C Brockton, Brockton, MA 02301 USA. EM robert_strecker@hms.harvard.edu RI McCarley, Robert/N-5562-2014; OI McCarley, Robert/0000-0001-5705-7495; Poeta, Devon/0000-0002-6286-7182 FU Department of Veterans Affairs Medical Research Service Award [T32 HL07901, R37 MH039683, P50 HL060292, HL095491]; Stonehill College FX This research was supported by the Department of Veterans Affairs Medical Research Service Award (R. E. S.), T32 HL07901 (Y.K.), R37 MH039683 (R. W. M.), P50 HL060292 (R. E. S. and R. W. M.), HL095491 (R. W. M. and R. E. S.), Stonehill College (J.G.M., D. L. P., R.B.). NR 25 TC 9 Z9 10 U1 1 U2 34 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JAN 23 PY 2013 VL 24 IS 2 BP 91 EP 95 DI 10.1097/WNR.0b013e32835cd97a PG 5 WC Neurosciences SC Neurosciences & Neurology GA 064IC UT WOS:000313066600008 PM 23238166 ER PT J AU Kelly, AD Haibe-Kains, B Janeway, KA Hill, KE Howe, E Goldsmith, J Kurek, K Perez-Atayde, AR Francoeur, N Fan, JB April, C Schneider, H Gebhardt, MC Culhane, A Quackenbush, J Spentzos, D AF Kelly, Andrew D. Haibe-Kains, Benjamin Janeway, Katherine A. Hill, Katherine E. Howe, Eleanor Goldsmith, Jeffrey Kurek, Kyle Perez-Atayde, Antonio R. Francoeur, Nancy Fan, Jian-Bing April, Craig Schneider, Hal Gebhardt, Mark C. Culhane, Aedin Quackenbush, John Spentzos, Dimitrios TI MicroRNA paraffin-based studies in osteosarcoma reveal reproducible independent prognostic profiles at 14q32 SO GENOME MEDICINE LA English DT Article ID GENOME-DASL ASSAY; GENE-EXPRESSION; ILLUMINA MICROARRAY; BREAST-CANCER; CELLS; ASSOCIATION; SIGNATURE; PLATFORM; SAMPLES; RNA AB Background: Although microRNAs (miRNAs) are implicated in osteosarcoma biology and chemoresponse, miRNA prognostic models are still needed, particularly because prognosis is imperfectly correlated with chemoresponse. Formalin-fixed, paraffin-embedded tissue is a necessary resource for biomarker studies in this malignancy with limited frozen tissue availability. Methods: We performed miRNA and mRNA microarray formalin-fixed, paraffin-embedded assays in 65 osteosarcoma biopsy and 26 paired post-chemotherapy resection specimens and used the only publicly available miRNA dataset, generated independently by another group, to externally validate our strongest findings (n = 29). We used supervised principal components analysis and logistic regression for survival and chemoresponse, and miRNA activity and target gene set analysis to study miRNA regulatory activity. Results: Several miRNA-based models with as few as five miRNAs were prognostic independently of pathologically assessed chemoresponse (median recurrence-free survival: 59 months versus not-yet-reached; adjusted hazards ratio = 2.90; P = 0.036). The independent dataset supported the reproducibility of recurrence and survival findings. The prognostic value of the profile was independent of confounding by known prognostic variables, including chemoresponse, tumor location and metastasis at diagnosis. Model performance improved when chemoresponse was added as a covariate (median recurrence-free survival: 59 months versus not-yet-reached; hazard ratio = 3.91; P = 0.002). Most prognostic miRNAs were located at 14q32 - a locus already linked to osteosarcoma - and their gene targets display deregulation patterns associated with outcome. We also identified miRNA profiles predictive of chemoresponse (75% to 80% accuracy), which did not overlap with prognostic profiles. Conclusions: Formalin-fixed, paraffin-embedded tissue-derived miRNA patterns are a powerful prognostic tool for risk-stratified osteosarcoma management strategies. Combined miRNA and mRNA analysis supports a possible role of the 14q32 locus in osteosarcoma progression and outcome. Our study creates a paradigm for formalin-fixed, paraffin-embedded-based miRNA biomarker studies in cancer. C1 [Kelly, Andrew D.; Hill, Katherine E.; Francoeur, Nancy; Spentzos, Dimitrios] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol,Sarcoma Program,Dept Med, Boston, MA 02215 USA. [Haibe-Kains, Benjamin; Howe, Eleanor; Culhane, Aedin; Quackenbush, John] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Ctr Canc Computat Biol, Boston, MA 02215 USA. [Haibe-Kains, Benjamin] Inst Rech Clin Montreal, Montreal, PQ H2W 1R7, Canada. [Janeway, Katherine A.] Harvard Univ, Boston Childrens Hosp, Sch Med, Div Hematol Oncol,Dept Med, Boston, MA 02215 USA. [Goldsmith, Jeffrey] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. [Kurek, Kyle; Perez-Atayde, Antonio R.] Harvard Univ, Boston Childrens Hosp, Sch Med, Dept Pathol, Boston, MA 02215 USA. [Fan, Jian-Bing; April, Craig] Illumina Inc, San Diego, CA 92122 USA. [Schneider, Hal] Harvard Univ, Boston Childrens Hosp, Sch Med, Mol Genet Core Facil, Boston, MA 02215 USA. [Gebhardt, Mark C.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Orthoped Surg, Boston, MA 02215 USA. RP Spentzos, D (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hematol Oncol,Sarcoma Program,Dept Med, 330 Brookline Ave, Boston, MA 02215 USA. EM dspentzo@bidmc.harvard.edu RI Haibe-Kains, Benjamin/D-3702-2011; OI Haibe-Kains, Benjamin/0000-0002-7684-0079; Kelly, Andrew/0000-0002-5338-7689 FU National Institutes of Health [K22 CA138716-01A2, U19 CA148065]; Dana Farber Cancer Institute Strategic Plan Fund; Balsamos Fund at Beth Israel Deaconess Medical Center FX The authors would like to thank the following institutions for the funding provided for this study: the National Institutes of Health (K22 CA138716-01A2 to DS and U19 CA148065 to JQ); the Dana Farber Cancer Institute Strategic Plan Fund (to JQ); the Balsamos Fund at Beth Israel Deaconess Medical Center (to DS and MCG), and a donation by Dr Richard and Virginia Clemmer to the sarcoma program at Beth Israel Deaconess Medical Center, (to DS and MCG). NR 44 TC 14 Z9 16 U1 0 U2 7 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 22 PY 2013 VL 5 AR 2 DI 10.1186/gm406 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 143YR UT WOS:000318905800001 PM 23339462 ER PT J AU Wegmann, S Medalsy, ID Mandelkow, E Muller, DJ AF Wegmann, Susanne Medalsy, Izhar D. Mandelkow, Eckhard Mueller, Daniel J. TI The fuzzy coat of pathological human Tau fibrils is a two-layered polyelectrolyte brush SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE protein aggregation; Alzheimer's disease; paired helical filaments ID PAIRED HELICAL FILAMENTS; MICROTUBULE-ASSOCIATED PROTEIN; ALZHEIMERS-DISEASE; ELECTRON-MICROSCOPY; BETA-STRUCTURE; LIVING CELLS; CORE DOMAIN; IN-VITRO; PHOSPHORYLATION; MODEL AB The structure and properties of amyloid-like Tau fibrils accumulating in neurodegenerative diseases have been debated for decades. Although the core of Tau fibrils assembles from short beta-strands, the properties of the much longer unstructured Tau domains protruding from the fibril core remain largely obscure. Applying immunogold transmission EM, and force-volume atomic force microscopy (AFM), we imaged human Tau fibrils at high resolution and simultaneously mapped their mechanical and adhesive properties. Tau fibrils showed a approximate to 16-nm-thick fuzzy coat that resembles a two-layered polyelectrolyte brush, which is formed by the unstructured short C-terminal and long N-terminal Tau domains. The mechanical and adhesive properties of the fuzzy coat are modulated by electrolytes and pH, and thus by the cellular environment. These unique properties of the fuzzy coat help in understanding how Tau fibrils disturb cellular interactions and accumulate in neurofibrillary tangles. C1 [Wegmann, Susanne; Medalsy, Izhar D.; Mueller, Daniel J.] ETH, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland. [Wegmann, Susanne] Harvard Univ, Dept Neurol, Charlestown, MA 02129 USA. [Wegmann, Susanne] Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. [Mandelkow, Eckhard] German Ctr Neurodegenerat Dis, D-53175 Bonn, Germany. [Mandelkow, Eckhard] Ctr Adv European Studies & Res, D-53175 Bonn, Germany. [Mandelkow, Eckhard] Hamburg Outstn, Max Planck Inst Neurol Res Cologne, D-22607 Hamburg, Germany. RP Wegmann, S (reprint author), ETH, Dept Biosyst Sci & Engn, CH-4058 Basel, Switzerland. EM susanne.wegmann@partners.org; daniel.mueller@bsse.ethz.ch RI Muller, Daniel/A-5967-2010 OI Muller, Daniel/0000-0003-3075-0665 FU M. DiFiglia and the Philly Dake EM center at the Massassachusetts General Hospital; European Molecular Biology Organization; Eidgenossiche Technische Hochschule; Deutsche Forschungsgemeinschaft; Max-Planck-Gesellschaft; Deutsches Zentrum fur Neurodegenerative Erkrankungen; Swiss National Science Foundation FX We thank J. Helenius, E. M. Mandelkow, B. T. Hyman, and T. Spires-Jones for critical discussions, and S. Chinnathambi and P. Bosshart for experimental assistance. We also thank M. DiFiglia and the Philly Dake EM center at the Massassachusetts General Hospital for support. This work was supported by the European Molecular Biology Organization, Eidgenossiche Technische Hochschule, Deutsche Forschungsgemeinschaft, Max-Planck-Gesellschaft, Deutsches Zentrum fur Neurodegenerative Erkrankungen, and Swiss National Science Foundation. NR 52 TC 33 Z9 33 U1 1 U2 43 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 22 PY 2013 VL 110 IS 4 BP E313 EP E321 DI 10.1073/pnas.1212100110 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 083HK UT WOS:000314453900009 PM 23269837 ER PT J AU Afilalo, J Flynn, AW Shimony, A Rudski, LG Agnihotri, AK Morin, JF Castrillo, C Shahian, DM Picard, MH AF Afilalo, Jonathan Flynn, Aidan W. Shimony, Avi Rudski, Lawrence G. Agnihotri, Arvind K. Morin, Jean-Francois Castrillo, Cristina Shahian, David M. Picard, Michael H. TI Incremental Value of the Preoperative Echocardiogram to Predict Mortality and Major Morbidity in Coronary Artery Bypass Surgery SO CIRCULATION LA English DT Article DE coronary artery bypass; echocardiography; outcome assessment (health care); surgery; ventricular function, right ID RIGHT-VENTRICULAR FUNCTION; CARDIAC-SURGERY; PULMONARY-HYPERTENSION; DIASTOLIC DYSFUNCTION; ISCHEMIC CARDIOMYOPATHY; EUROPEAN-ASSOCIATION; THORACIC SURGEONS; AMERICAN-SOCIETY; GRAFTING SURGERY; OF-CARDIOLOGY AB Background-Although echocardiography is commonly performed before coronary artery bypass surgery, there has yet to be a study examining the incremental prognostic value of a complete echocardiogram. Methods and Results-Patients undergoing isolated coronary artery bypass surgery at 2 hospitals were divided into derivation and validation cohorts. A panel of quantitative echocardiographic parameters was measured. Clinical variables were extracted from the Society of Thoracic Surgeons database. The primary outcome was in-hospital mortality or major morbidity, and the secondary outcome was long-term all-cause mortality. The derivation cohort consisted of 667 patients with a mean age of 67.2 +/- 11.1 years and 22.8% females. The following echocardiographic parameters were found to be optimal predictors of mortality or major morbidity: severe diastolic dysfunction, as evidenced by restrictive filling (odds ratio, 2.96; 95% confidence interval, 1.59-5.49), right ventricular dysfunction, as evidenced by fractional area change <35% (odds ratio, 3.03; 95% confidence interval, 1.28-7.20), or myocardial performance index >0.40 (odds ratio, 1.89; 95% confidence interval, 1.13-3.15). These results were confirmed in the validation cohort of 187 patients. When added to the Society of Thoracic Surgeons risk score, the echocardiographic parameters resulted in a net improvement in model discrimination and reclassification with a change in c-statistic from 0.68 to 0.73 and an integrated discrimination improvement of 5.9% (95% confidence interval, 2.8%-8.9%). In the Cox proportional hazards model, right ventricular dysfunction and pulmonary hypertension were independently predictive of mortality over 3.2 years of follow-up. Conclusions-Preoperative echocardiography, in particular right ventricular dysfunction and restrictive left ventricular filling, provides incremental prognostic value in identifying patients at higher risk of mortality or major morbidity after coronary artery bypass surgery. (Circulation. 2013; 127: 356-364.) C1 [Afilalo, Jonathan; Flynn, Aidan W.; Castrillo, Cristina; Picard, Michael H.] Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Agnihotri, Arvind K.; Shahian, David M.] Harvard Univ, Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. [Shahian, David M.] Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Shahian, David M.] Harvard Univ, Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02114 USA. [Afilalo, Jonathan; Shimony, Avi; Rudski, Lawrence G.] McGill Univ, Jewish Gen Hosp, Div Cardiol, Cardiac Ultrasound Lab, Montreal, PQ H3T 1E2, Canada. [Morin, Jean-Francois] McGill Univ, Jewish Gen Hosp, Div Cardiac Surg, Montreal, PQ H3T 1E2, Canada. RP Afilalo, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Cardiac Ultrasound Lab, 55 Fruit St,Yawkey 5E, Boston, MA 02114 USA. EM jonathan@afilalo.com OI Picard, Michael/0000-0002-9264-3243 FU Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Institutes of Health award) [UL1 RR 025758]; Harvard Catalyst \ The Harvard Clinical and Translational Science Center ( Harvard University); FRSQ (Fonds de Recherche Sante du Quebec) Research Fellowship Award FX We thank Dr Murray Mittleman for his expertise and guidance. This work was conducted with support from Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (National Institutes of Health award #UL1 RR 025758 and financial contributions from Harvard University and its affiliated academic health care 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 health care centers, the National Center for Research Resources, or the National Institutes of Health.; Dr Afilalo was supported by the FRSQ (Fonds de Recherche Sante du Quebec) Research Fellowship Award. NR 47 TC 17 Z9 17 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 22 PY 2013 VL 127 IS 3 BP 356 EP + DI 10.1161/CIRCULATIONAHA.112.127639 PG 16 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 073KG UT WOS:000313741300016 PM 23239840 ER PT J AU Cade, F Cruzat, A Paschalis, EI Santo, LE Pineda, R AF Cade, Fabiano Cruzat, Andrea Paschalis, Eleftherios I. Santo, Lilian Espirito Pineda, Roberto TI Analysis of Four Aberrometers for Evaluating Lower and Higher Order Aberrations SO PLOS ONE LA English DT Article ID FOURIER-TRANSFORMS; WAVE-ABERRATION; PUPIL LOCATION; ZERNIKE; EYE; PRINCIPLES; LADARWAVE; HISTORY; QUALITY; ERRORS AB Purpose: To compare the measurements of lower and higher order aberrations (HOA) of 4 commonly used aberrometers. Setting: Massachusetts Eye & Ear Infirmary, Boston, USA. Design: Prospective, cross-sectional study, in a controlled, single-blinded fashion. Methods: Multiple readings were obtained in 42 eyes of 21 healthy volunteers, at a single visit, with each of the following aberrometers: Alcon LADARWave (R), Visx WaveScan (R), B & L Zywave (R), and Wavelight Allegro Analyzer (R). Results were compared and analyzed in regards to the lower and HOA, to the different wavefront sensing devices and software, Tscherning and Hartmann-Shack and between the Fourier and Zernike algorithms. Statistical analysis included Bland-Altman plots, Intraclass Correlation Coefficient (ICC), multiple comparison tests with Analysis of Variance and Kruskal-Wallis. Significant level was set to p<0.05 and alpha level correction was adjusted under the Bonferroni criteria. Results: Most measurements of all 4 aberrometers were comparable. However, statistically significant differences were found between the aberrometers in total HOA (tHOA), spherical aberration (SA), horizontal coma and astigmatism (2,2). LADARwave and Wavescan showed significant differences in tHOA (P<0.001, ICC = 0.549, LoA = 0.19 +/- 0.5) and in SA (P<0.001, ICC = 0.733, LoA = 0.16 +/- 0.37). Wavescan showed a significant difference compared to Zywave (p<0.001, ICC = 0.920, LoA = 0.09 +/- 0.13) in SA. Comparisons between Allegro Analyzer and Zywave demonstrated significant differences in both Horizontal Coma (3,1) (p < 0.001, ICC = 20.207, LoA = -0.15 +/- 0.48) and Astigmatism (2,2) (P = 0.003, ICC = -0.965, LoA = 0.2 +/- 2.5). Allegro Analyzer also differed from Wavescan in Horizontal Coma (3,1) (P < 0.001, ICC = 0.725, LoA = -0.07 +/- 0.25). Conclusions: Although some measurements were comparable predominately in the lower order aberrations, significant differences were found in the tHOA, SA, horizontal coma and astigmatism. Our analysis suggests that sensor design contributes to agreement in lower order aberrations, and Fourier and Zernike expansion might disagree in higher order aberrations. Therefore, comparison between aberrometers was generally possible with some exceptions in higher order measurements. C1 [Cade, Fabiano; Cruzat, Andrea; Paschalis, Eleftherios I.; Santo, Lilian Espirito; Pineda, Roberto] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. RP Paschalis, EI (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. EM Eleftherios_paschalis@meei.harvard.edu OI Cruzat, Andrea/0000-0002-3724-7037; Paschalis, Eleftherios/0000-0002-4544-4452 FU Alcon FX Financial support: R.P. (Alcon), unrestricted grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 31 TC 4 Z9 4 U1 2 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 22 PY 2013 VL 8 IS 1 AR e54990 DI 10.1371/journal.pone.0054990 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 077HS UT WOS:000314019100116 PM 23349995 ER PT J AU Meydan, C Otu, HH Sezerman, OU AF Meydan, Cem Otu, Hasan H. Sezerman, Osman Ugur TI Prediction of peptides binding to MHC class I and II alleles by temporal motif mining SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 11th Asia Pacific Bioinformatics Conference (APBC) CY JAN 21-24, 2013 CL Vancouver, CANADA ID T-CELL EPITOPES; MOLECULES; SURVIVAL; LIGANDS; PROTEIN; TOOLS; BULGE AB Background: MHC (Major Histocompatibility Complex) is a key player in the immune response of most vertebrates. The computational prediction of whether a given antigenic peptide will bind to a specific MHC allele is important in the development of vaccines for emerging pathogens, the creation of possibilities for controlling immune response, and for the applications of immunotherapy. One of the problems that make this computational prediction difficult is the detection of the binding core region in peptides, coupled with the presence of bulges and loops causing variations in the total sequence length. Most machine learning methods require the sequences to be of the same length to successfully discover the binding motifs, ignoring the length variance in both motif mining and prediction steps. In order to overcome this limitation, we propose the use of time-based motif mining methods that work position-independently. Results: The prediction method was tested on a benchmark set of 28 different alleles for MHC class I and 27 different alleles for MHC class II. The obtained results are comparable to the state of the art methods for both MHC classes, surpassing the published results for some alleles. The average prediction AUC values are 0.897 for class I, and 0.858 for class II. Conclusions: Temporal motif mining using partial periodic patterns can capture information about the sequences well enough to predict the binding of the peptides and is comparable to state of the art methods in the literature. Unlike neural networks or matrix based predictors, our proposed method does not depend on peptide length and can work with both short and long fragments. This advantage allows better use of the available training data and the prediction of peptides of uncommon lengths. C1 [Meydan, Cem; Sezerman, Osman Ugur] Sabanci Univ, Dept Bioengn, TR-34956 Istanbul, Turkey. [Otu, Hasan H.] Harvard Univ, Sch Med, Dept Med, BIDMC Genom Ctr, Boston, MA 02215 USA. [Otu, Hasan H.] Istanbul Bilgi Univ, Dept Bioengn, TR-34060 Istanbul, Turkey. RP Sezerman, OU (reprint author), Sabanci Univ, Dept Bioengn, TR-34956 Istanbul, Turkey. EM ugur@sabanciuniv.edu NR 40 TC 5 Z9 5 U1 0 U2 19 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JAN 21 PY 2013 VL 14 SU 2 AR S13 DI 10.1186/1471-2105-14-S2-S13 PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 083MK UT WOS:000314468200013 PM 23368521 ER PT J AU Paganelli, C Peroni, M Riboldi, M Sharp, GC Ciardo, D Alterio, D Orecchia, R Baroni, G AF Paganelli, Chiara Peroni, Marta Riboldi, Marco Sharp, Gregory C. Ciardo, Delia Alterio, Daniela Orecchia, Roberto Baroni, Guido TI Scale invariant feature transform in adaptive radiation therapy: a tool for deformable image registration assessment and re-planning indication SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID COMPUTED-TOMOGRAPHY; HEAD; RADIOTHERAPY AB Adaptive radiation therapy (ART) aims at compensating for anatomic and pathological changes to improve delivery along a treatment fraction sequence. Current ART protocols require time-consuming manual updating of all volumes of interest on the images acquired during treatment. Deformable image registration (DIR) and contour propagation stand as a state of the ART method to automate the process, but the lack of DIR quality control methods hinder an introduction into clinical practice. We investigated the scale invariant feature transform (SIFT) method as a quantitative automated tool (1) for DIR evaluation and (2) for re-planning decision-making in the framework of ART treatments. As a preliminary test, SIFT invariance properties at shape-preserving and deformable transformations were studied on a computational phantom, granting residual matching errors below the voxel dimension. Then a clinical dataset composed of 19 head and neck ART patients was used to quantify the performance in ART treatments. For the goal (1) results demonstrated SIFT potential as an operator-independent DIR quality assessment metric. We measured DIR group systematic residual errors up to 0.66 mm against 1.35 mm provided by rigid registration. The group systematic errors of both bony and all other structures were also analyzed, attesting the presence of anatomical deformations. The correct automated identification of 18 patients who might benefit from ART out of the total 22 cases using SIFT demonstrated its capabilities toward goal (2) achievement. C1 [Paganelli, Chiara; Peroni, Marta; Riboldi, Marco; Baroni, Guido] Politecn Milan, Dept Bioengn, Milan, Italy. [Riboldi, Marco; Orecchia, Roberto; Baroni, Guido] Ctr Nazl Adroterapia Oncol, Dept Med, Pavia, Italy. [Sharp, Gregory C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Ciardo, Delia; Alterio, Daniela; Orecchia, Roberto] European Inst Oncol, Div Radiotherapy, Milan, Italy. [Orecchia, Roberto] Univ Milan, Milan, Italy. RP Paganelli, C (reprint author), Politecn Milan, Dept Bioengn, Milan, Italy. EM marco.riboldi@polimi.it RI Riboldi, Marco/I-2980-2014 OI Riboldi, Marco/0000-0002-2431-4966 FU AIRC, Italian Association for Cancer Research FX The work was partially supported by AIRC, Italian Association for Cancer Research. NR 29 TC 26 Z9 29 U1 0 U2 16 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JAN 21 PY 2013 VL 58 IS 2 BP 287 EP 299 DI 10.1088/0031-9155/58/2/287 PG 13 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 058ZQ UT WOS:000312674400009 PM 23257263 ER PT J AU Cassioli, A Unkelbach, J AF Cassioli, A. Unkelbach, J. TI Aperture shape optimization for IMRT treatment planning SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID GENETIC ALGORITHM; RADIATION-THERAPY; COLUMN GENERATION; SHOOT IMRT; RADIOTHERAPY; SEGMENTS AB We propose an algorithm for aperture shape optimization (ASO) for step and shoot delivery of intensity-modulated radiotherapy. The method is an approach to direct aperture optimization (DAO) that exploits gradient information to locally optimize the positions of the leafs of a multileaf collimator. Based on the dose-influence matrix, the dose distribution is locally approximated as a linear function of the leaf positions. Since this approximation is valid only in a small interval around the current leaf positions, we use a trust-region like method to optimize the leaf positions: in one iteration, the leaf motion is confined to the beamlets where the leaf edges are currently positioned. This yields a well-behaved optimization problem for the leaf positions and the aperture weights, which can be solved efficiently. If, in one iteration, a leaf is moved to the edge of a beamlet, the leaf motion can be confined to the neighboring beamlet in the next iteration. This allows for large leaf position changes over the course of the algorithm. In this paper, the ASO algorithm is embedded into a column-generation approach to DAO. After a new aperture is added to the treatment plan, we use the ASO algorithm to simultaneously optimize aperture weights and leaf positions for the new set of apertures. We present results for a paraspinal tumor case, a prostate case and a head and neck case. The computational results indicate that, using this approach, treatment plans close to the ideal fluence map optimization solution can be obtained. C1 [Cassioli, A.; Unkelbach, J.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Cassioli, A (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 30 Fruit St, Boston, MA 02114 USA. EM cassioliandre@gmail.com; junkelbach@partners.org NR 17 TC 10 Z9 10 U1 1 U2 7 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JAN 21 PY 2013 VL 58 IS 2 BP 301 EP 318 DI 10.1088/0031-9155/58/2/301 PG 18 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 058ZQ UT WOS:000312674400010 PM 23257284 ER PT J AU Ghobrial, IM AF Ghobrial, Irene M. TI Choice of Therapy for Patients With Waldenstrom Macroglobulinemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID PHASE-II TRIAL; EXTENDED RITUXIMAB THERAPY; INTERNATIONAL WORKSHOP; TREATMENT RECOMMENDATIONS; UNTREATED PATIENTS; WEEKLY BORTEZOMIB; FLUDARABINE; CYCLOPHOSPHAMIDE; COMBINATION; DISEASE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ghobrial, IM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 42 TC 4 Z9 6 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2013 VL 31 IS 3 BP 291 EP 293 DI 10.1200/JCO.2012.46.6177 PG 3 WC Oncology SC Oncology GA 074DV UT WOS:000313793700005 PM 23233705 ER PT J AU Flaherty, KT Lee, SJ Zhao, FM Schuchter, LM Flaherty, L Kefford, R Atkins, MB Leming, P Kirkwood, JM AF Flaherty, Keith T. Lee, Sandra J. Zhao, Fengmin Schuchter, Lynn M. Flaherty, Lawrence Kefford, Richard Atkins, Michael B. Leming, Philip Kirkwood, John M. TI Phase III Trial of Carboplatin and Paclitaxel With or Without Sorafenib in Metastatic Melanoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RENAL-CELL CARCINOMA; STAGE-IV MELANOMA; MULTIKINASE INHIBITOR; COLORECTAL-CANCER; PROGRESSION-FREE; BEVACIZUMAB; COMBINATION; DACARBAZINE; SURVIVAL; MULTICENTER AB Purpose The primary objective of this study was to determine whether carboplatin, paclitaxel, and sorafenib (CPS) improve overall survival (OS) compared with carboplatin and paclitaxel (CP) in chemotherapy-naive patients with metastatic melanoma. Patients and Methods In this double-blind, randomized, placebo-controlled phase III study, all patients received carboplatin at area under the [concentration-time] curve 6 and paclitaxel 225 mg/m(2) intravenously once every 21 days with random assignment to sorafenib 400 mg orally twice per day on days 2 through 19 every 21 days or placebo. The primary end point was OS, and secondary end points included progression-free survival, objective tumor response, and toxicity. Results In all, 823 patients were enrolled over 34 months. At final analysis, the median OS was 11.3 months (95% CI, 9.8 to 12.2 months) for CP and 11.1 months (95% CI, 10.3 to 12.3 months) for CPS; the difference in the OS distribution was not statistically significant by the stratified log-rank test, stratified on American Joint Committee on Cancer (AJCC) stage, Eastern Cooperative Oncology Group (ECOG) performance status, and prior therapy (P = .878). Median progression-free survival was 4.9 months for CPS and 4.2 months for CP (P = .092, stratified log-rank test). Response rate was 20% for CPS and 18% for CP (P = .427). More patients on the CPS arm had grade 3 or higher toxicities (84% v 78%; P = .027), with increased rash, hand-foot syndrome, and thrombocytopenia accounting for most of the difference. Conclusion Sorafenib does not improve OS when given in combination with CP for chemotherapy-naive patients with metastatic melanoma. This study establishes benchmark end points for the CP regimen in first-line therapy of metastatic melanoma. J Clin Oncol 31:373-379. (C) 2012 by American Society of Clinical Oncology C1 [Flaherty, Keith T.; Schuchter, Lynn M.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Kirkwood, John M.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Lee, Sandra J.; Zhao, Fengmin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Atkins, Michael B.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Flaherty, Lawrence] Wayne State Univ, Karmanos Canc Ctr, Detroit, MI USA. [Kefford, Richard] Univ Sydney, Westmead Hosp, Sydney, NSW 2006, Australia. [Leming, Philip] Cincinnati Hematol Oncol, Cincinnati, OH USA. RP Flaherty, KT (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM kflaherty@partners.org FU CureTech; Genentech; GlaxoSmithKline; Merck FX Although all authors completed the disclosure declaration, the following author(s) and/or an author's immediate family member(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors. Employment or Leadership Position: None Consultant or Advisory Role: Keith T. Flaherty, Onyx Pharmaceuticals (C); Lynn M. Schuchter, Merck (C) Stock Ownership: None Honoraria: None Research Funding: Lynn M. Schuchter, CureTech, Genentech, GlaxoSmithKline, Merck Expert Testimony: None Other Remuneration: None NR 28 TC 72 Z9 72 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2013 VL 31 IS 3 BP 373 EP 379 DI 10.1200/JCO.2012.42.1529 PG 7 WC Oncology SC Oncology GA 074DV UT WOS:000313793700019 PM 23248256 ER PT J AU Volandes, AE Paasche-Orlow, MK Mitchell, SL El-Jawahri, A Davis, AD Barry, MJ Hartshorn, KL Jackson, VA Gillick, MR Walker-Corkery, ES Chang, YC Lopez, L Kemeny, M Bulone, L Mann, E Misra, S Peachey, M Abbo, ED Eichler, AF Epstein, AS Noy, A Levin, TT Temel, JS AF Volandes, Angelo E. Paasche-Orlow, Michael K. Mitchell, Susan L. El-Jawahri, Areej Davis, Aretha Delight Barry, Michael J. Hartshorn, Kevan L. Jackson, Vicki Ann Gillick, Muriel R. Walker-Corkery, Elizabeth S. Chang, Yuchiao Lopez, Lenny Kemeny, Margaret Bulone, Linda Mann, Eileen Misra, Sumi Peachey, Matt Abbo, Elmer D. Eichler, April F. Epstein, Andrew S. Noy, Ariela Levin, Tomer T. Temel, Jennifer S. TI Randomized Controlled Trial of a Video Decision Support Tool for Cardiopulmonary Resuscitation Decision Making in Advanced Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LIMITED HEALTH LITERACY; PATIENT; CARE; LIFE; END; QUALITY; AIDS; COMMUNICATION; PREFERENCES; PHYSICIANS AB Purpose Decision making regarding cardiopulmonary resuscitation (CPR) is challenging. This study examined the effect of a video decision support tool on CPR preferences among patients with advanced cancer. Patients and Methods We performed a randomized controlled trial of 150 patients with advanced cancer from four oncology centers. Participants in the control arm (n = 80) listened to a verbal narrative describing CPR and the likelihood of successful resuscitation. Participants in the intervention arm (n = 70) listened to the identical narrative and viewed a 3-minute video depicting a patient on a ventilator and CPR being performed on a simulated patient. The primary outcome was participants' preference for or against CPR measured immediately after exposure to either modality. Secondary outcomes were participants' knowledge of CPR (score range of 0 to 4, with higher score indicating more knowledge) and comfort with video. Results The mean age of participants was 62 years (standard deviation, 11 years); 49% were women, 44% were African American or Latino, and 47% had lung or colon cancer. After the verbal narrative, in the control arm, 38 participants (48%) wanted CPR, 41 (51%) wanted no CPR, and one (1%) was uncertain. In contrast, in the intervention arm, 14 participants (20%) wanted CPR, 55 (79%) wanted no CPR, and 1 (1%) was uncertain (unadjusted odds ratio, 3.5; 95% CI, 1.7 to 7.2; P < .001). Mean knowledge scores were higher in the intervention arm than in the control arm (3.3 +/- 1.0 v 2.6 +/- 1.3, respectively; P < .001), and 65 participants (93%) in the intervention arm were comfortable watching the video. Conclusion Participants with advanced cancer who viewed a video of CPR were less likely to opt for CPR than those who listened to a verbal narrative. J Clin Oncol 31:380-386. (C) 2012 by American Society of Clinical Oncology C1 [Volandes, Angelo E.; El-Jawahri, Areej; Barry, Michael J.; Jackson, Vicki Ann; Walker-Corkery, Elizabeth S.; Chang, Yuchiao; Lopez, Lenny; Mann, Eileen; Eichler, April F.; Temel, Jennifer S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Volandes, Angelo E.; Mitchell, Susan L.; El-Jawahri, Areej; Davis, Aretha Delight; Barry, Michael J.; Jackson, Vicki Ann; Gillick, Muriel R.; Walker-Corkery, Elizabeth S.; Chang, Yuchiao; Lopez, Lenny; Mann, Eileen; Eichler, April F.; Temel, Jennifer S.] Harvard Univ, Sch Med, Boston, MA USA. [Paasche-Orlow, Michael K.; Hartshorn, Kevan L.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Mitchell, Susan L.] Hebrew Senior Life, Inst Aging Res, Boston, MA USA. [Gillick, Muriel R.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Davis, Aretha Delight] Mt Auburn Hosp, Cambridge, MA USA. [Kemeny, Margaret] Mt Sinai Sch Med, New York, NY USA. [Kemeny, Margaret; Bulone, Linda] Queens Hosp Canc Ctr, New York, NY USA. [Epstein, Andrew S.; Noy, Ariela; Levin, Tomer T.] Mem Sloan Kettering Comprehens Canc Ctr, New York, NY USA. [Epstein, Andrew S.; Noy, Ariela; Levin, Tomer T.] Weill Cornell Med Coll, New York, NY USA. [Misra, Sumi; Peachey, Matt] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Misra, Sumi] Nashville Vet Affairs Hosp, Nashville, TN USA. [Abbo, Elmer D.] Univ Chicago, Chicago, IL 60637 USA. RP Volandes, AE (reprint author), Massachusetts Gen Hosp, Gen Med Unit, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM avolandes@partners.org RI Levin, Tomer/D-2997-2016; OI Levin, Tomer/0000-0001-5054-5103; Hartshorn, Kevan/0000-0002-7196-7433; Paasche-Orlow, Michael/0000-0002-9276-7190; Noy, Ariela/0000-0002-3001-4898 FU Agency for Healthcare Research and Quality [K08HS018780]; Informed Medical Decisions Foundation [0177-1] FX Supported by Grant No. K08HS018780 from the Agency for Healthcare Research and Quality (A.E.V.) and by a grant from the Informed Medical Decisions Foundation (Research Grant No. 0177-1). NR 33 TC 40 Z9 40 U1 3 U2 13 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2013 VL 31 IS 3 BP 380 EP 386 DI 10.1200/JCO.2012.43.9570 PG 7 WC Oncology SC Oncology GA 074DV UT WOS:000313793700020 PM 23233708 ER PT J AU Shoni, M Parra-Herran, CE May, T Wright, AA Feltmate, CM AF Shoni, Melina Parra-Herran, Carlos E. May, Taymaa Wright, Alexi A. Feltmate, Colleen M. TI Multiple Synchronous Primary Gynecologic Malignancies in an MSH2 Mutation Carrier With Endometriosis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; LYNCH-SYNDROME; MICROSATELLITE INSTABILITY; OVARIAN-CANCER; ATYPICAL ENDOMETRIOSIS; PROPHYLACTIC SURGERY; ASSOCIATION; TRANSFORMATION; CARCINOMAS; RISK C1 [Shoni, Melina; May, Taymaa; Feltmate, Colleen M.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. [Parra-Herran, Carlos E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Wright, Alexi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Shoni, M (reprint author), Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. OI Parra-Herran, Carlos/0000-0003-1420-7291 NR 40 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2013 VL 31 IS 3 BP E33 EP E36 DI 10.1200/JCO.2012.43.4274 PG 4 WC Oncology SC Oncology GA 074DV UT WOS:000313793700001 PM 23213089 ER PT J AU Prates, RA Fuchs, BB Mizuno, K Naqvi, Q Kato, IT Ribeiro, MS Mylonakis, E Tegos, GP Hamblin, MR AF Prates, Renato A. Fuchs, Beth Burgwyn Mizuno, Kazue Naqvi, Qurat Kato, Ilka T. Ribeiro, Martha S. Mylonakis, Eleftherios Tegos, George P. Hamblin, Michael R. TI Effect of Virulence Factors on the Photodynamic Inactivation of Cryptococcus neoformans SO PLOS ONE LA English DT Article ID SELECTIVE ANTIMICROBIAL PHOTOSENSITIZERS; RESISTANT STAPHYLOCOCCUS-AUREUS; CELL-WALL INTEGRITY; CANDIDA-ALBICANS; IN-VITRO; ANTIFUNGAL AGENTS; SACCHAROMYCES-CEREVISIAE; FUNGAL-INFECTIONS; OXIDATIVE STRESS; VISIBLE-LIGHT AB Opportunistic fungal pathogens may cause an array of superficial infections or serious invasive infections, especially in immunocompromised patients. Cryptococcus neoformans is a pathogen causing cryptococcosis in HIV/AIDS patients, but treatment is limited due to the relative lack of potent antifungal agents. Photodynamic inactivation (PDI) uses the combination of non-toxic dyes called photosensitizers and harmless visible light, which produces singlet oxygen and other reactive oxygen species that produce cell inactivation and death. We report the use of five structurally unrelated photosensitizers (methylene blue, Rose Bengal, selenium derivative of a Nile blue dye, a cationic fullerene and a conjugate between poly-L-lysine and chlorin(e6)) combined with appropriate wavelengths of light to inactivate C. neoformans. Mutants lacking capsule and laccase, and culture conditions that favoured melanin production were used to probe the mechanisms of PDI and the effect of virulence factors. The presence of cell wall, laccase and melanin tended to protect against PDI, but the choice of the appropriate photosensitizers and dosimetry was able to overcome this resistance. C1 [Prates, Renato A.; Kato, Ilka T.; Ribeiro, Martha S.] Nucl & Energy Res Inst, Ctr Lasers & Applicat, Sao Paulo, Brazil. [Prates, Renato A.] Univ Nove Julho, Sch Dent, Dept Hlth, Sao Paulo, Brazil. [Fuchs, Beth Burgwyn; Mylonakis, Eleftherios] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Prates, Renato A.; Mizuno, Kazue; Naqvi, Qurat; Tegos, George P.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Prates, Renato A.; Mizuno, Kazue; Tegos, George P.; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Tegos, George P.] Univ New Mexico, Dept Pathol, Sch Med, Albuquerque, NM 87131 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Tegos, GP (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM GTegos@salud.unm.edu; Hamblin@helix.mgh.harvard.edu RI Kato, Ilka/G-7644-2012; Prates, Renato/F-8235-2014; Ribeiro, Martha/G-3517-2012; OI Ribeiro, Martha/0000-0002-4203-1134; Hamblin, Michael/0000-0001-6431-4605 FU FAPESP [2010/13313 9]; Brazilian National Commission on Research (CNPq) [501499/2011 3]; United States National Institutes of Health (NIH) [R01A1050875, R01CA137108]; US Air Force MFEL Program [FA9550-04-1-0079]; NIH [5U54MH084690-02]; DTRA [HDTRA1-13-C-0005] FX This work was partially supported by FAPESP (2010/13313 9) and Brazilian National Commission on Research (CNPq grant 501499/2011 3). Research in the Hamblin laboratory was supported by United States National Institutes of Health (NIH) grants (R01A1050875 to MRH and R01CA137108 to Long Y. Chiang) and US Air Force MFEL Program (FA9550-04-1-0079). George P. Tegos was supported by the NIH (grant 5U54MH084690-02) and DTRA (contract HDTRA1-13-C-0005). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 68 TC 7 Z9 7 U1 0 U2 25 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 18 PY 2013 VL 8 IS 1 AR e54387 DI 10.1371/journal.pone.0054387 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 075GQ UT WOS:000313872800047 PM 23349872 ER PT J AU Gymrek, M McGuire, AL Golan, D Halperin, E Erlich, Y AF Gymrek, Melissa McGuire, Amy L. Golan, David Halperin, Eran Erlich, Yaniv TI Identifying Personal Genomes by Surname Inference SO SCIENCE LA English DT Article ID Y-STR LOCI; CHROMOSOME; PRIVACY; FOUNDERS; PROJECT; SCIENCE AB Sharing sequencing data sets without identifiers has become a common practice in genomics. Here, we report that surnames can be recovered from personal genomes by profiling short tandem repeats on the Y chromosome (Y-STRs) and querying recreational genetic genealogy databases. We show that a combination of a surname with other types of metadata, such as age and state, can be used to triangulate the identity of the target. A key feature of this technique is that it entirely relies on free, publicly accessible Internet resources. We quantitatively analyze the probability of identification for U.S. males. We further demonstrate the feasibility of this technique by tracing back with high probability the identities of multiple participants in public sequencing projects. C1 [Gymrek, Melissa; Erlich, Yaniv] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Gymrek, Melissa] MIT, Harvard Massachusetts Inst Technol MIT Div Hlth S, Cambridge, MA 02139 USA. [Gymrek, Melissa] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Gymrek, Melissa] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Gymrek, Melissa] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [McGuire, Amy L.] Baylor Coll Med, Ctr Med Eth & Hlth Policy, Houston, TX 77030 USA. [Golan, David] Tel Aviv Univ, Dept Stat & Operat Res, IL-69978 Tel Aviv, Israel. [Halperin, Eran] Tel Aviv Univ, Sch Comp Sci, IL-69978 Tel Aviv, Israel. [Halperin, Eran] Tel Aviv Univ, Dept Mol Microbiol & Biotechnol, IL-69978 Tel Aviv, Israel. [Halperin, Eran] Int Comp Sci Inst, Berkeley, CA 94704 USA. RP Erlich, Y (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM yaniv@wi.mit.edu OI /0000-0002-6086-3903 FU National Defense Science and Engineering Graduate Fellowship; Edmond J. Safra Center for Bioinformatics at Tel-Aviv University FX We thank FamilyTreeDNA and SMGF for technical assistance. We also thank D. Esposito, A. Goren, G. Fink, D. Page, W. Kramer, and R. Ronen for useful discussions. Y.E. is an Andria and Paul Heafy Family Fellow. This publication was supported by a gift from Jim and Cathy Stone (Y. E.), the National Defense Science and Engineering Graduate Fellowship (M. G.), and the Edmond J. Safra Center for Bioinformatics at Tel-Aviv University (D. G. and E. H.). NR 27 TC 276 Z9 277 U1 7 U2 72 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JAN 18 PY 2013 VL 339 IS 6117 BP 321 EP 324 DI 10.1126/science.1229566 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 071UW UT WOS:000313622000045 PM 23329047 ER PT J AU Ma, LL Borwankar, AU Willsey, BW Yoon, KY Tam, JO Sokolov, KV Feldman, MD Milner, TE Johnston, KP AF Ma, L. L. Borwankar, A. U. Willsey, B. W. Yoon, K. Y. Tam, J. O. Sokolov, K. V. Feldman, M. D. Milner, T. E. Johnston, K. P. TI Growth of textured thin Au coatings on iron oxide nanoparticles with near infrared absorbance SO NANOTECHNOLOGY LA English DT Article ID MAGNETIC NANOPARTICLES; GOLD NANOPARTICLES; OPTICAL-PROPERTIES; SHELL NANOPARTICLES; FE OXIDE; SIZE; CORE; NANOCRYSTALS; REDUCTION; NANOSHELLS AB A homologous series of Au coated iron oxide nanoparticles with hydrodynamic diameters smaller than 60 nm was synthesized with very low Au-to-iron mass ratios, as low as 0.15. The hydrodynamic diameter was determined by dynamic light scattering and the composition by atomic absorption spectroscopy and energy dispersive x-ray spectroscopy. Unusually low Au precursor supersaturation levels were utilized to nucleate and grow Au coatings on iron oxide relative to the formation of pure Au nanoparticles. This approach produced unusually thin coatings by lowering autocatalytic growth of Au on Au, as shown by transmission electron microscopy. Nearly all of the nanoparticles were attracted by a magnet, indicating a minimal number of pure Au particles. The coatings were sufficiently thin to shift the surface plasmon resonance to the near infrared with large extinction coefficients, despite the small particle hydrodynamic diameters observed from dynamic light scattering to be less than 60 nm. C1 [Ma, L. L.; Borwankar, A. U.; Willsey, B. W.; Yoon, K. Y.; Johnston, K. P.] Univ Texas Austin, Dept Chem Engn, Austin, TX 78712 USA. [Ma, L. L.; Feldman, M. D.] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Tam, J. O.; Sokolov, K. V.; Milner, T. E.] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA. [Sokolov, K. V.] Univ Texas MD Anderson Canc Ctr, Dept Biomed Engn, Houston, TX 77030 USA. [Sokolov, K. V.] Univ Texas MD Anderson Canc Ctr, Dept Imaging Phys, Houston, TX 77030 USA. [Feldman, M. D.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Cardiol, San Antonio, TX 78229 USA. RP Ma, LL (reprint author), Univ Texas Austin, Dept Chem Engn, Austin, TX 78712 USA. EM kpj@che.utexas.edu OI Sokolov, Konstantin/0000-0002-0198-2005; Ma, Li/0000-0002-0959-5616 FU STC Program of the National Science Foundation [CHE-9876674]; Welch Foundation [F-1319]; NIH [RO1 EB008821-01, NIH RO1 CA 143663]; NSF [CBET-0968038]; Veterans Hospital Administration Merit Grant; National Natural Science Foundation of China [81000113] FX This work is supported in part by the STC Program of the National Science Foundation under Agreement CHE-9876674, Welch Foundation (F-1319), NIH RO1 EB008821-01, NIH RO1 CA 143663, NSF CBET-0968038 and Veterans Hospital Administration Merit Grant. Dr Li Leo Ma acknowledges partial support from the National Natural Science Foundation of China (81000113). NR 72 TC 4 Z9 4 U1 0 U2 76 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0957-4484 EI 1361-6528 J9 NANOTECHNOLOGY JI Nanotechnology PD JAN 18 PY 2013 VL 24 IS 2 AR 025606 DI 10.1088/0957-4484/24/2/025606 PG 14 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Science & Technology - Other Topics; Materials Science; Physics GA 057UF UT WOS:000312588800017 PM 23238021 ER PT J AU Bakis, Y Otu, HH Tasci, N Meydan, C Bilgin, N Yuzbasioglu, S Sezerman, OU AF Bakis, Yasin Otu, Hasan H. Tasci, Nivart Meydan, Cem Bilgin, Nes'e Yuzbasioglu, Sirri Sezerman, O. Ugur TI Testing robustness of relative complexity measure method constructing robust phylogenetic trees for Galanthus L. Using the relative complexity measure SO BMC BIOINFORMATICS LA English DT Article DE Resampling; Alignment free; Phylogenetics; Relative Complexity Measure; Galanthus ID MULTIPLE SEQUENCE ALIGNMENT; DNA; CONFIDENCE; BOOTSTRAP; INFERENCE; PROTEIN; ACCURACY; FAMILIES AB Background: Most phylogeny analysis methods based on molecular sequences use multiple alignment where the quality of the alignment, which is dependent on the alignment parameters, determines the accuracy of the resulting trees. Different parameter combinations chosen for the multiple alignment may result in different phylogenies. A new non-alignment based approach, Relative Complexity Measure (RCM), has been introduced to tackle this problem and proven to work in fungi and mitochondrial DNA. Result: In this work, we present an application of the RCM method to reconstruct robust phylogenetic trees using sequence data for genus Galanthus obtained from different regions in Turkey. Phylogenies have been analyzed using nuclear and chloroplast DNA sequences. Results showed that, the tree obtained from nuclear ribosomal RNA gene sequences was more robust, while the tree obtained from the chloroplast DNA showed a higher degree of variation. Conclusions: Phylogenies generated by Relative Complexity Measure were found to be robust and results of RCM were more reliable than the compared techniques. Particularly, to overcome MSA-based problems, RCM seems to be a reasonable way and a good alternative to MSA-based phylogenetic analysis. We believe our method will become a mainstream phylogeny construction method especially for the highly variable sequence families where the accuracy of the MSA heavily depends on the alignment parameters. C1 [Bakis, Yasin] Abant Izzet Baysal Univ, Dept Biol, TR-14280 Bolu, Turkey. [Otu, Hasan H.] Harvard Univ, Sch Med, Dept Med, BIDMC Genom Ctr, Boston, MA 02115 USA. [Otu, Hasan H.] Istanbul Bilgi Univ, Dept Genet & Bioengn, TR-34060 Istanbul, Turkey. [Tasci, Nivart; Bilgin, Nes'e] Bogazici Univ, Dept Mol Biol & Genet, TR-34342 Istanbul, Turkey. [Meydan, Cem; Sezerman, O. Ugur] Sabanci Univ, TR-34956 Istanbul, Turkey. [Yuzbasioglu, Sirri] Istanbul Univ, Dept Bot, TR-34460 Istanbul, Turkey. RP Bakis, Y (reprint author), Abant Izzet Baysal Univ, Dept Biol, TR-14280 Bolu, Turkey. EM bakis_y@ibu.edu.tr RI Bilgin, Nese/E-7163-2013; OI Otu, Hasan/0000-0002-9253-8152 FU Turkish Scientific and Technological Research Council (TUBITAK) [105T341]; Dubai Harvard Foundation for Medical Research FX Experimental part of this work is supported by the Turkish Scientific and Technological Research Council (TUBITAK) (grant number 105T341). The Grant has been given to Prof. Dr. Tuna Ekim. HHO is partially supported by a grant from The Dubai Harvard Foundation for Medical Research. NR 47 TC 3 Z9 3 U1 0 U2 17 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JAN 17 PY 2013 VL 14 AR 20 DI 10.1186/1471-2105-14-20 PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 084ZQ UT WOS:000314580800001 PM 23323678 ER PT J AU Chen, XL Shen, YP Gao, YH Zhao, HZ Sheng, XM Zou, JZ Lip, V Xie, H Guo, J Shao, H Bao, YH Shen, JL Niu, B Gusella, JF Wu, BL Zhang, T AF Chen, Xiaoli Shen, Yiping Gao, Yonghui Zhao, Huizhi Sheng, Xiaoming Zou, Jizhen Lip, Va Xie, Hua Guo, Jin Shao, Hong Bao, Yihua Shen, Jianliang Niu, Bo Gusella, James F. Wu, Bai-Lin Zhang, Ting TI Detection of Copy Number Variants Reveals Association of Cilia Genes with Neural Tube Defects SO PLOS ONE LA English DT Article ID CELL POLARITY GENE; HIGH-RISK AREA; SHANXI PROVINCE; CLOSURE DEFECTS; HIGH PREVALENCE; AUTOPSY SERIES; ARRAY CGH; MUTATIONS; CHINA; POLYMORPHISMS AB Background: Neural tube defects (NTDs) are one of the most common birth defects caused by a combination of genetic and environmental factors. Currently, little is known about the genetic basis of NTDs although up to 70% of human NTDs were reported to be attributed to genetic factors. Here we performed genome-wide copy number variants (CNVs) detection in a cohort of Chinese NTD patients in order to exam the potential role of CNVs in the pathogenesis of NTDs. Methods: The genomic DNA from eighty-five NTD cases and seventy-five matched normal controls were subjected for whole genome CNVs analysis. Non-DGV (the Database of Genomic Variants) CNVs from each group were further analyzed for their associations with NTDs. Gene content in non-DGV CNVs as well as participating pathways were examined. Results: Fifty-five and twenty-six non-DGV CNVs were detected in cases and controls respectively. Among them, forty and nineteen CNVs involve genes (genic CNV). Significantly more non-DGV CNVs and non-DGV genic CNVs were detected in NTD patients than in control (41.2% vs. 25.3%, p<0.05 and 37.6% vs. 20%, p<0.05). Non-DGV genic CNVs are associated with a 2.65-fold increased risk for NTDs (95% CI: 1.24-5.87). Interestingly, there are 41 cilia genes involved in non-DGV CNVs from NTD patients which is significantly enriched in cases compared with that in controls (24.7% vs. 9.3%, p<0.05), corresponding with a 3.19-fold increased risk for NTDs (95% CI: 1.27-8.01). Pathway analyses further suggested that two ciliogenesis pathways, tight junction and protein kinase A signaling, are top canonical pathways implicated in NTD-specific CNVs, and these two novel pathways interact with known NTD pathways. Conclusions: Evidence from the genome-wide CNV study suggests that genic CNVs, particularly ciliogenic CNVs are associated with NTDs and two ciliogenesis pathways, tight junction and protein kinase A signaling, are potential pathways involved in NTD pathogenesis. C1 [Chen, Xiaoli; Gao, Yonghui; Zhao, Huizhi; Xie, Hua; Guo, Jin; Bao, Yihua; Zhang, Ting] Capital Inst Pediat, Beijing, Peoples R China. [Chen, Xiaoli; Shen, Yiping; Sheng, Xiaoming; Lip, Va; Shao, Hong; Wu, Bai-Lin] Childrens Hosp Boston, Dept Lab Med, Boston, MA 02115 USA. [Chen, Xiaoli; Shen, Yiping; Gusella, James F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Shen, Yiping] Jiao Tong Univ, Shanghai Childrens Med Ctr, Shanghai 200030, Peoples R China. [Shen, Yiping; Gusella, James F.; Wu, Bai-Lin] Harvard Univ, Sch Med, Boston, MA USA. [Gao, Yonghui] China Acad Chinese Med Sci, Inst Acumoxibust, Beijing, Peoples R China. [Zou, Jizhen] Capital Inst Pediat, Dept Pathol, Beijing, Peoples R China. [Shen, Jianliang] Navy Gen Hosp PLA, Dept Hematol, Beijing, Peoples R China. [Niu, Bo] Capital Inst Pediat, Dept Biotechnol, Beijing, Peoples R China. [Wu, Bai-Lin] Fudan Univ, Shanghai Med Coll, Childrens Hosp, Shanghai 200433, Peoples R China. [Wu, Bai-Lin] Fudan Univ, Shanghai Med Coll, Inst Biomed Sci, Shanghai 200433, Peoples R China. RP Wu, BL (reprint author), Childrens Hosp Boston, Dept Lab Med, Boston, MA 02115 USA. EM Bai-Lin.Wu@childrens.harvard.edu; zhangtingcv@yahoo.com.cn FU Ministry of Science and Technology of P. R. China; National "973" Program on Population and Health [2013CB945404, 2010CB529601]; National Nature Science Fund [81100841]; Beijing Excellent Scientist Fund [20061A0303200108]; Chinese Returned Oversea Scientist Fund; Beijing Science and Technology; Shanghai Science Fund [09JC1402400, 09ZR1404500] FX This work was jointly supported by the Ministry of Science and Technology of P. R. China, the National "973" Program on Population and Health (2013CB945404 to TZ; 2010CB529601 to BLW), the National Nature Science Fund (81100841 to XLC), the Beijing Excellent Scientist Fund (20061A0303200108 to XLC), Chinese Returned Oversea Scientist Fund to XLC by Beijing Science and Technology, and the Shanghai Science Fund (09JC1402400 and 09ZR1404500 to BLW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 67 TC 7 Z9 9 U1 0 U2 17 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 17 PY 2013 VL 8 IS 1 AR e54492 DI 10.1371/journal.pone.0054492 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 073JI UT WOS:000313738900072 PM 23349908 ER PT J AU Wu, B Peisley, A Richards, C Yao, H Zeng, XH Lin, C Chu, FX Walz, T Hur, S AF Wu, Bin Peisley, Alys Richards, Claire Yao, Hui Zeng, Xiaohui Lin, Cecilie Chu, Feixia Walz, Thomas Hur, Sun TI Structural Basis for dsRNA Recognition, Filament Formation, and Antiviral Signal Activation by MDA5 SO CELL LA English DT Article ID DOUBLE-STRANDED-RNA; RECEPTOR RIG-I; INNATE IMMUNE-RESPONSE; PATTERN-RECOGNITION; VIRAL-RNA; SENSOR; MECHANISM; HELICASE; INSIGHTS; DOMAINS AB MDA5, a viral double-stranded RNA (dsRNA) receptor, shares sequence similarity and signaling pathways with RIG-I yet plays essential functions in antiviral immunity through distinct specificity for viral RNA. Revealing the molecular basis for the functional divergence, we report here the crystal structure of MDA5 bound to dsRNA, which shows how, using the same domain architecture, MDA5 recognizes the internal duplex structure, whereas RIG-I recognizes the terminus of dsRNA. We further show that MDA5 uses direct protein-protein contacts to stack along dsRNA in a head-to-tail arrangement, and that the signaling domain (tandem CARD), which decorates the outside of the core MDA5 filament, also has an intrinsic propensity to oligomerize into an elongated structure that activates the signaling adaptor, MAVS. These data support a model in which MDA5 uses long dsRNA as a signaling platform to cooperatively assemble the core filament, which in turn promotes stochastic assembly of the tandem CARD oligomers for signaling. C1 [Wu, Bin; Peisley, Alys; Hur, Sun] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Lin, Cecilie; Walz, Thomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Wu, Bin; Peisley, Alys; Richards, Claire; Hur, Sun] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Yao, Hui] Nankai Univ, Dept Biochem & Mol Biol, Tianjin 300071, Peoples R China. [Zeng, Xiaohui; Chu, Feixia] Univ New Hampshire, Dept Mol Cellular & Biomed Sci, Durham, NH 03824 USA. [Walz, Thomas] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Hur, S (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM hur@idi.harvard.edu RI Wu, Bin/C-4715-2015 FU NIFA/USDA [H00567]; UNH Karabelis Fund; Pew Scholarship FX The authors thank the NE-CAT beamline scientists for their assistance during data collection. F.C. acknowledges NIFA/USDA H00567 and UNH Karabelis Fund. T.W. is an Investigator in the Howard Hughes Medical Institute. S.H. is the recipient of a Pew Scholarship. NR 25 TC 141 Z9 142 U1 1 U2 41 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JAN 17 PY 2013 VL 152 IS 1-2 BP 276 EP 289 DI 10.1016/j.cell.2012.11.048 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 073CA UT WOS:000313719800023 PM 23273991 ER PT J AU Yan, J Xiang, JL Lin, YT Ma, JG Zhang, JY Zhang, H Sun, JS Danial, NN Liu, J Lin, AN AF Yan, Jie Xiang, Jialing Lin, Yutin Ma, Jingui Zhang, Jiyan Zhang, Hao Sun, Jisheng Danial, Nika N. Liu, Jing Lin, Anning TI Inactivation of BAD by IKK Inhibits TNF alpha-Induced Apoptosis Independently of NF-kappa B Activation SO CELL LA English DT Article ID TUMOR-NECROSIS-FACTOR; SEVERE LIVER DEGENERATION; CELL-DEATH; TRANSCRIPTION FACTORS; SIGNAL-TRANSDUCTION; FEEDBACK INHIBITION; KINASE ACTIVATION; JNK ACTIVATION; DEFICIENT MICE; PHOSPHORYLATION AB The I kappa B kinase complex (IKK) is a key regulator of immune responses, inflammation, cell survival, and tumorigenesis. The prosurvival function of IKK centers on activation of the transcription factor NF-kappa B, whose target gene products inhibit caspases and prevent prolonged JNK activation. Here, we report that inactivation of the BH3-only protein BAD by IKK independently of NF-kappa B activation suppresses TNF alpha-induced apoptosis. TNF alpha-treated Ikk beta(-/-) mouse embryonic fibroblasts (MEFs) undergo apoptosis significantly faster than MEFs deficient in both RelA and cRel due to lack of inhibition of BAD by IKK. IKK phosphorylates BAD at serine-26 (Ser26) and primes it for inactivation. Elimination of Ser26 phosphorylation promotes BAD proapoptotic activity, thereby accelerating TNF alpha-induced apoptosis in cultured cells and increasing mortality in animals. Our results reveal that IKK inhibits TNF alpha-induced apoptosis through two distinct but cooperative mechanisms: activation of the survival facto r NF-kappa B and inactivation of the proapoptotic BH3-only BAD protein. C1 [Yan, Jie; Ma, Jingui; Zhang, Jiyan; Lin, Anning] Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA. [Xiang, Jialing; Lin, Yutin] IIT, Dept Biol & Chem Sci, Chicago, IL 60616 USA. [Zhang, Jiyan] Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China. [Zhang, Hao; Sun, Jisheng; Lin, Anning] Chinese Acad Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China. [Danial, Nika N.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Liu, Jing] Northwestern Univ, Feinberg Sch Med, Div Pulm & Crit Care Med, Chicago, IL 60611 USA. RP Lin, AN (reprint author), Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA. EM anninglin@bsd.uchicago.edu FU National Basic Research Program of China [2012CB910801]; National Natural Science Foundation of China [31130035]; Chinese Academy of Sciences [SIBS2010CSP001]; National Institutes of Health [CA100460, CA128114, GM081603] FX We are grateful to Drs. David A. Brenner, Joseph A. DiDonato, Michael Karin, Stanley Korsmeyer, and Frank Mercurio for reagents that make this work possible. This work is partially supported by National Basic Research Program of China (2012CB910801), National Natural Science Foundation of China (31130035), Chinese Academy of Sciences (SIBS2010CSP001), and National Institutes of Health grants CA100460 (to A.L.), CA128114 (to J.X.), and GM081603 (to J.L.). NR 45 TC 29 Z9 30 U1 1 U2 38 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JAN 17 PY 2013 VL 152 IS 1-2 BP 304 EP 315 DI 10.1016/j.cell.2012.12.021 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 073CA UT WOS:000313719800025 PM 23332762 ER PT J AU Burd, CE Sorrentino, JA Clark, KS Darr, DB Krishnamurthy, J Deal, AM Bardeesy, N Castrillon, DH Beach, DH Sharpless, NE AF Burd, Christin E. Sorrentino, Jessica A. Clark, Kelly S. Darr, David B. Krishnamurthy, Janakiraman Deal, Allison M. Bardeesy, Nabeel Castrillon, Diego H. Beach, David H. Sharpless, Norman E. TI Monitoring Tumorigenesis and Senescence In Vivo with a p16(INK4a)-Luciferase Model SO CELL LA English DT Article ID P16(INK4A) TUMOR-SUPPRESSOR; CELLULAR SENESCENCE; FIBROBLAST SENESCENCE; METASTATIC MELANOMA; TRANSGENIC MICE; STEM-CELLS; LIFE-SPAN; T-CELLS; EXPRESSION; CANCER AB Monitoring cancer and aging in vivo remains experimentally challenging. Here, we describe a luciferase knockin mouse (p16(LUC)), which faithfully reports expression of p16(INK4a), a tumor suppressor and aging biomarker. Lifelong assessment of luminescence in p16(+/LUC) mice revealed an exponential increase with aging, which was highly variable in a cohort of contemporaneously housed, syngeneic mice. Expression of p16(INK4a) with aging did not predict cancer development, suggesting that the accumulation of senescent cells is not a principal determinant of cancer-related death. In 14 of 14 tested tumor models, expression of p16(LUC) was focally activated by early neoplastic events, enabling visualization of tumors with sensitivity exceeding other imaging modalities. Activation of p16(INK4a) was noted in the emerging neoplasm and surrounding stromal cells. This work suggests that p16(INK4a) activation is a characteristic of all emerging cancers, making the p16(LUC) allele a sensitive, unbiased reporter of neoplastic transformation. C1 [Burd, Christin E.; Clark, Kelly S.; Darr, David B.; Krishnamurthy, Janakiraman; Sharpless, Norman E.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC 27599 USA. [Burd, Christin E.; Clark, Kelly S.; Darr, David B.; Krishnamurthy, Janakiraman; Sharpless, Norman E.] Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC 27599 USA. [Burd, Christin E.; Sorrentino, Jessica A.; Clark, Kelly S.; Darr, David B.; Krishnamurthy, Janakiraman; Deal, Allison M.; Sharpless, Norman E.] Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Bardeesy, Nabeel] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Canc Ctr, Boston, MA 02114 USA. [Castrillon, Diego H.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. [Beach, David H.] Barts & London Queen Marys Sch Med & Dent, Blizard Inst, London E1 2AT, England. RP Sharpless, NE (reprint author), Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC 27599 USA. EM nes@med.unc.edu FU NIH [AG024379, CA137181, CA163896, AG036817]; Paul Glenn Foundation; Burroughs Wellcome Fund FX We thank H. Yuan, K. Guley, and the UNC BRIC Small Animal Imaging Facility for imaging assistance; A. Moisan (MGH Cancer) for technical assistance; C.G. Pena (UT Southwestern), E.A. Akbay (UT Southwestern), D.T. Gammons (UNC), W.Y. Kim (UNC), and W. Liu (UNC) for providing reagents; the UNC Animal Clinical Chemistry, Animal Histopathology, and Gene Expression Laboratories, as well as G. Aloisio (UT Southwestern), for tissue processing and routine genotyping; the UNC Microscopy Services Laboratory and UNC Animal Studies facility for technical assistance; and the UNC Mouse Phase I unit for providing animals and expertise. This work was supported by the NIH (AG024379; CA137181; CA163896; AG036817), the Paul Glenn Foundation, and the Burroughs Wellcome Fund. NR 64 TC 76 Z9 76 U1 3 U2 44 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JAN 17 PY 2013 VL 152 IS 1-2 BP 340 EP 351 DI 10.1016/j.cell.2012.12.010 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 073CA UT WOS:000313719800028 PM 23332765 ER PT J AU Ebert, DH Greenberg, ME AF Ebert, Daniel H. Greenberg, Michael E. TI Activity-dependent neuronal signalling and autism spectrum disorder SO NATURE LA English DT Review ID X MENTAL-RETARDATION; DE-NOVO MUTATIONS; DENDRITIC SPINE MORPHOLOGY; LONG-TERM DEPRESSION; FRAGILE-X; MOUSE MODEL; SYNAPTIC PLASTICITY; BDNF TRANSCRIPTION; RETT-SYNDROME; FMRP PHOSPHORYLATION AB Neuronal activity induces the post-translational modification of synaptic molecules, promotes localized protein synthesis within dendrites and activates gene transcription, thereby regulating synaptic function and allowing neuronal circuits to respond dynamically to experience. Evidence indicates that many of the genes that are mutated in autism spectrum disorder are crucial components of the activity-dependent signalling networks that regulate synapse development and plasticity. Dysregulation of activity-dependent signalling pathways in neurons may, therefore, have a key role in the aetiology of autism spectrum disorder. C1 [Ebert, Daniel H.; Greenberg, Michael E.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Ebert, Daniel H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. RP Greenberg, ME (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. EM michael_greenberg@hms.harvard.edu FU NIH [RO1NS048276, K08MH90306]; Rett Syndrome Research Trust FX M.E.G. is supported by NIH grant RO1NS048276 and the Rett Syndrome Research Trust. D.H.E. is supported by NIH grant K08MH90306. NR 98 TC 175 Z9 184 U1 13 U2 137 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 17 PY 2013 VL 493 IS 7432 BP 327 EP 337 DI 10.1038/nature11860 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 071TA UT WOS:000313615900039 PM 23325215 ER PT J AU Le, T Wright, EJ Smith, DM He, WJ Catano, G Okulicz, JF Young, JA Clark, RA Richman, DD Little, SJ Ahuja, SK AF Le, Tuan Wright, Edwina J. Smith, Davey M. He, Weijing Catano, Gabriel Okulicz, Jason F. Young, Jason A. Clark, Robert A. Richman, Douglas D. Little, Susan J. Ahuja, Sunil K. TI Enhanced CD4+T-Cell Recovery with Earlier HIV-1 Antiretroviral Therapy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LYMPHOID-TISSUE STRUCTURE; SOCIETY-USA PANEL; T-CELLS; PRIMARY INFECTION; AIDS; SEROCONVERSION; CD4; RECOMMENDATIONS; RECONSTITUTION AB Background The relationship between the timing of the initiation of antiretroviral therapy (ART) after infection with human immunodeficiency virus type 1 (HIV-1) and the recovery of CD4+ T-cell counts is unknown. Methods In a prospective, observational cohort of persons with acute or early HIV-1 infection, we determined the trajectory of CD4+ counts over a 48-month period in partially overlapping study sets: study set 1 included 384 participants during the time window in which they were not receiving ART and study set 2 included 213 participants who received ART soon after study entry or sometime thereafter and had a suppressed plasma HIV viral load. We investigated the likelihood and rate of CD4+ T-cell recovery to 900 or more cells per cubic millimeter within 48 months while the participants were receiving viral-load-suppressive ART. Results Among the participants who were not receiving ART, CD4+ counts increased spontaneously, soon after HIV-1 infection, from the level at study entry (median, 495 cells per cubic millimeter; interquartile range, 383 to 622), reached a peak value (median, 763 cells per cubic millimeter; interquartile range, 573 to 987) within approximately 4 months after the estimated date of infection, and declined progressively thereafter. Recovery of CD4+ counts to 900 or more cells per cubic millimeter was seen in approximately 64% of the participants who initiated ART earlier (<= 4 months after the estimated date of HIV infection) as compared with approximately 34% of participants who initiated ART later (>4 months) (P<0.001). After adjustment for whether ART was initiated when the CD4+ count was 500 or more cells per cubic millimeter or less than 500 cells per cubic millimeter, the likelihood that the count would increase to 900 or more cells per cubic millimeter was lower by 65% (odds ratio, 0.35), and the rate of recovery was slower by 56% (rate ratio, 0.44), if ART was initiated later rather than earlier. There was no association between the plasma HIV RNA level at the time of initiation of ART and CD4+ T-cell recovery. Conclusions A transient, spontaneous restoration of CD4+ T-cell counts occurs in the 4-month time window after HIV-1 infection. Initiation of ART during this period is associated with an enhanced likelihood of recovery of CD4+ counts. (Funded by the National Institute of Allergy and Infectious Diseases and others.) C1 [Le, Tuan; He, Weijing; Catano, Gabriel; Clark, Robert A.; Ahuja, Sunil K.] S Texas Vet Hlth Care Syst, Vet Affairs Res Ctr AIDS & HIV Infect 1, San Antonio, TX 78229 USA. [Le, Tuan; He, Weijing; Catano, Gabriel; Clark, Robert A.; Ahuja, Sunil K.] S Texas Vet Hlth Care Syst, Ctr Personalized Med, San Antonio, TX USA. [Le, Tuan; He, Weijing; Catano, Gabriel; Clark, Robert A.; Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Microbiol & Immunol, San Antonio, TX 78229 USA. [Ahuja, Sunil K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Okulicz, Jason F.] San Antonio Mil Med Ctr, Infect Dis Serv, Ft Sam Houston, TX USA. [Wright, Edwina J.] Monash Univ, Alfred Hosp, Dept Infect Dis, Burnet Inst, Melbourne, Vic 3181, Australia. [Wright, Edwina J.] Monash Univ, Dept Infect Dis, Melbourne, Vic 3004, Australia. [Smith, Davey M.; Richman, Douglas D.] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. [Smith, Davey M.; Young, Jason A.; Richman, Douglas D.; Little, Susan J.] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Richman, Douglas D.] Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. RP Ahuja, SK (reprint author), S Texas Vet Hlth Care Syst, Vet Affairs Res Ctr AIDS & HIV Infect 1, San Antonio, TX 78229 USA. EM slittle@ucsd.edu; ahujas@uthscsa.edu FU Veterans Affairs (VA) Center for AIDS and HIV Infection; VA Center for Personalized Medicine of the South Texas Veterans Health Care System; National Institutes of Health (NIH) [UL1TR000149, R37 AI046326]; NIH [AI43638, AI69432, MH62512, AI74621, MH083552, AI077304, AI007384, AI080193, AI096113]; International AIDS Vaccine Initiative [DMS0714991]; California HIV/AIDS Research Program [RN07-SD-702]; VA Career Development Award-2; National Health and Medical Research Council of Australia; Doris Duke Distinguished Clinical Scientist Award, a VA MERIT; Elizabeth Glaser Pediatric AIDS Foundation; Burroughs Welcome Clinical Scientist Award in Translational Research; Senior Scholar Award from the Max and Minnie Tomerlin Voelcker Fund FX Supported by the Veterans Affairs (VA) Center for AIDS and HIV Infection and VA Center for Personalized Medicine of the South Texas Veterans Health Care System and a MERIT grant (R37 AI046326) and a Clinical and Translational Science Award (UL1TR000149) from the National Institutes of Health (NIH) (all for the work at San Antonio) and by grants from the NIH (AI43638, AI69432, MH62512, AI74621, MH083552, AI077304, AI007384, AI080193, and AI096113), the International AIDS Vaccine Initiative (DMS0714991), and the California HIV/AIDS Research Program (RN07-SD-702) (all for the work at San Diego). Dr. Le was supported by a VA Career Development Award-2, Dr. Wright by an Early Career Fellowship from the National Health and Medical Research Council of Australia, and Dr. Ahuja by the Doris Duke Distinguished Clinical Scientist Award, a VA MERIT award, the Elizabeth Glaser Pediatric AIDS Foundation, the Burroughs Welcome Clinical Scientist Award in Translational Research, and the Senior Scholar Award from the Max and Minnie Tomerlin Voelcker Fund. NR 33 TC 143 Z9 144 U1 0 U2 22 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 17 PY 2013 VL 368 IS 3 BP 218 EP 230 DI 10.1056/NEJMoa1110187 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 070YG UT WOS:000313549900006 PM 23323898 ER PT J AU Stankovic, KM Eskandar, E El Khoury, JB Lev, MH Sadow, PM AF Stankovic, Konstantina M. Eskandar, Emad El Khoury, Joseph B. Lev, Michael H. Sadow, Peter M. TI Case 2-2013: A 20-Year-Old Man with Recurrent Ear Pain, Fever, and Headache Cholesteatoma and cholesterol granuloma associated with chronic otitis media, with intracranial and extracranial complications SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BACTERIOLOGY; ADULTS C1 [Stankovic, Konstantina M.; Sadow, Peter M.] Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. [Eskandar, Emad] Harvard Univ, Sch Med, Dept Neurosurg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [El Khoury, Joseph B.] Harvard Univ, Sch Med, Dept Infect Dis, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Lev, Michael H.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Sadow, Peter M.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Stankovic, Konstantina M.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Eskandar, Emad] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [El Khoury, Joseph B.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Lev, Michael H.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Sadow, Peter M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Stankovic, Konstantina M.] Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Stankovic, KM (reprint author), Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. FU Medtronic; GE Healthcare; Millennium Pharmaceuticals FX Dr. Eskandar reports receiving consulting fees from Medtronic; and Dr. Lev, research support from GE Healthcare and consulting fees from Millennium Pharmaceuticals. No other potential conflict of interest relevant to this article was reported. NR 16 TC 0 Z9 0 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 17 PY 2013 VL 368 IS 3 BP 267 EP 277 DI 10.1056/NEJMcpc1200089 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 070YG UT WOS:000313549900013 PM 23323904 ER PT J AU Walker, BD Hirsch, MS AF Walker, Bruce D. Hirsch, Martin S. TI Antiretroviral Therapy in Early HIV Infection SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Walker, Bruce D.] Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Walker, BD (reprint author), Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA. NR 12 TC 12 Z9 12 U1 0 U2 6 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 17 PY 2013 VL 368 IS 3 BP 279 EP 281 DI 10.1056/NEJMe1213734 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 070YG UT WOS:000313549900014 PM 23323905 ER PT J AU Ogino, S Liao, XY Chan, AT AF Ogino, Shuji Liao, Xiaoyun Chan, Andrew T. TI Aspirin, PIK3CA Mutation, and Colorectal-Cancer Survival REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Ogino, Shuji; Liao, Xiaoyun] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ogino, S (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu RI Chan, Andrew/D-3361-2013 NR 0 TC 4 Z9 4 U1 0 U2 8 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 17 PY 2013 VL 368 IS 3 BP 289 EP 290 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 070YG UT WOS:000313549900026 PM 23323913 ER PT J AU Casson, L Howell, L Mathews, LA Ferrer, M Southall, N Guha, R Keller, JM Thomas, C Siskind, LJ Beverly, LJ AF Casson, Lavona Howell, Lauren Mathews, Lesley A. Ferrer, Marc Southall, Noel Guha, Rajarshi Keller, Jonathan M. Thomas, Craig Siskind, Leah J. Beverly, Levi J. TI Inhibition of Ceramide Metabolism Sensitizes Human Leukemia Cells to Inhibition of BCL2-Like Proteins SO PLOS ONE LA English DT Article ID DAUNORUBICIN-INDUCED APOPTOSIS; ACUTE LYMPHOBLASTIC-LEUKEMIA; BCL-2 FAMILY PROTEINS; BH3 MIMETIC ABT-737; GLUCOSYLCERAMIDE SYNTHASE; SPHINGOSINE KINASE; MYELOID-LEUKEMIA; CARCINOMA-CELLS; IN-VITRO; PATHWAY AB The identification of novel combinations of effective cancer drugs is required for the successful treatment of cancer patients for a number of reasons. First, many "cancer specific" therapeutics display detrimental patient side-effects and second, there are almost no examples of single agent therapeutics that lead to cures. One strategy to decrease both the effective dose of individual drugs and the potential for therapeutic resistance is to combine drugs that regulate independent pathways that converge on cell death. BCL2-like family members are key proteins that regulate apoptosis. We conducted a screen to identify drugs that could be combined with an inhibitor of anti-apoptotic BCL2-like proteins, ABT-263, to kill human leukemia cells lines. We found that the combination of D,L-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) hydrochloride, an inhibitor of glucosylceramide synthase, potently synergized with ABT-263 in the killing of multiple human leukemia cell lines. Treatment of cells with PDMP and ABT-263 led to dramatic elevation of two pro-apoptotic sphingolipids, namely ceramide and sphingosine. Furthermore, treatment of cells with the sphingosine kinase inhibitor, SKi-II, also dramatically synergized with ABT-263 to kill leukemia cells and similarly increased ceramides and sphingosine. Data suggest that synergism with ABT-263 requires accumulation of ceramides and sphingosine, as AMP-deoxynojirimycin, (an inhibitor of the glycosphingolipid pathway) did not elevate ceramides or sphingosine and importantly did not sensitize cells to ABT-263 treatment. Taken together, our data suggest that combining inhibitors of anti-apoptotic BCL2-like proteins with drugs that alter the balance of bioactive sphingolipids will be a powerful combination for the treatment of human cancers. C1 [Casson, Lavona; Beverly, Levi J.] Univ Louisville, James Graham Brown Canc Ctr, Dept Med, Div Hematol & Oncol, Louisville, KY 40292 USA. [Howell, Lauren; Siskind, Leah J.] Med Sch S Carolina, S Carolina Coll Pharm, Dept Drug Discovery & Biomed Sci, Charleston, SC USA. [Mathews, Lesley A.; Ferrer, Marc; Southall, Noel; Guha, Rajarshi; Keller, Jonathan M.; Thomas, Craig] NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA. [Siskind, Leah J.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Beverly, Levi J.] NHGRI, Canc Biol & Genet Sect, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Siskind, LJ (reprint author), Med Sch S Carolina, S Carolina Coll Pharm, Dept Drug Discovery & Biomed Sci, Charleston, SC USA. EM Siskind@MUSC.edu; Levi.Beverly@Louisville.edu RI Southall, Noel/H-8991-2012 OI Southall, Noel/0000-0003-4500-880X FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [R01DK093462]; Cancer Center Support Grant [P30 CA138313]; NIH/NCRR COBRE in Lipidomics and Pathobiology [P20 RR17677]; National Institutes of Health, Molecular Targets COBRE [8P20GM103482-10]; Wendy Will Case Cancer Fund [GB220413]; Kosair Pediatric Cancer Research Program award; NIH Common Fund Molecular Libraries and Imaging Program [U54 MH084681] FX Research reported in this publication was supported by: National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, R01DK093462 (to LJS), the Lipidomics Shared Resource of the Hollings Cancer Center at the Medical University of South Carolina supported by a Cancer Center Support Grant (P30 CA138313), pilot project (to LJS) from the NIH/NCRR P20 RR17677 COBRE in Lipidomics and Pathobiology, National Institutes of Health, Molecular Targets COBRE, 8P20GM103482-10 (to LJB), Wendy Will Case Cancer Fund, GB220413 (to LJB), Kosair Pediatric Cancer Research Program award (to LJB). This research was partly supported by the NIH Common Fund Molecular Libraries and Imaging Program, Grant U54 MH084681. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 14 Z9 14 U1 1 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 16 PY 2013 VL 8 IS 1 AR e54525 DI 10.1371/journal.pone.0054525 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 072OV UT WOS:000313682700122 PM 23342165 ER PT J AU Rahnama, R Wang, MQ Dang, AC Kim, HT Kuo, AC AF Rahnama, Ruyan Wang, Miqi Dang, Alexis C. Kim, Hubert T. Kuo, Alfred C. TI Cytotoxicity of Local Anesthetics on Human Mesenchymal Stem Cells SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID ARTICULAR CHONDROCYTES; IN-VITRO; BUPIVACAINE; ARTHROSCOPY; CARTILAGE; CHONDROGENESIS; CHONDROLYSIS; ROPIVACAINE; LIDOCAINE; CATHETER AB Background: Local anesthetics are frequently delivered intra-articularly to provide perioperative pain control. Previous studies have shown that the commonly used drugs lidocaine, ropivacaine, and bupivacaine can be toxic to human chondrocytes. The present study was conducted to determine whether the toxic effects of local anesthetics on human chondrocytes also extend to human mesenchymal stem cells. Methods: Human mesenchymal stem cells from three healthy donors were grown in tissue culture and exposed to the following anesthetic treatments for sixty minutes: (1) 1% lidocaine, (2) 2% lidocaine, (3) 0.25% bupivacaine, (4) 0.5% bupivacaine, (5) 0.2% ropivacaine, and (6) 0.5% ropivacaine. The cells were then allowed to recover for twenty-four hours in regular growth media, and viability was measured with use of fluorescent staining for live cells or a luminescence assay for ATP content. Results: The live cell counts and ATP content were correlated (r(2) = 0.79), and 2% lidocaine was found to be significantly more toxic than all doses of bupivacaine and ropivacaine. Treatment with 1% lidocaine resulted in significantly fewer live cells (49%) compared with the control, and the live cell count was also significantly less than that for the other anesthetics. However, the ATP level in the 1% lidocaine group was not significantly lower than those in the other groups. Bupivacaine and ropivacaine did not exhibit significant differences in toxicity compared with the control or with each other. Conclusions: Ropivacaine and bupivacaine had limited toxicity in human mesenchymal stem cells. However, lidocaine could significantly decrease mesenchymal stem cell viability. Since other studies have shown ropivacaine to be less toxic to chondrocytes than bupivacaine, ropivacaine may be a safer intra-articular anesthetic. C1 [Rahnama, Ruyan] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Orthopaed Surg, San Francisco, CA 94121 USA. RP Rahnama, R (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Orthopaed Surg, 4150 Clement St,Box 112, San Francisco, CA 94121 USA. FU Department of Orthopaedic Surgery of the University of California San Francisco FX This work was performed with funding from the Department of Orthopaedic Surgery of the University of California San Francisco and with resources of the Veterans Affairs Medical Center, San Francisco, California. There was no external funding source. NR 27 TC 19 Z9 21 U1 0 U2 7 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD JAN 16 PY 2013 VL 95A IS 2 BP 132 EP 137 DI 10.2106/JBJS.K.01291 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 076BO UT WOS:000313931700007 PM 23324960 ER PT J AU Lou, S Duan, B Vong, L Lowell, BB Ma, QF AF Lou, Shan Duan, Bo Linh Vong Lowell, Bradford B. Ma, Qiufu TI Runx1 Controls Terminal Morphology and Mechanosensitivity of VGLUT3-expressing C-Mechanoreceptors SO JOURNAL OF NEUROSCIENCE LA English DT Article ID ROOT GANGLION NEURONS; VESICULAR GLUTAMATE TRANSPORTERS; MAMMALIAN SENSORY NEURONS; MERKEL CELLS; NEUROPATHIC PAIN; REGULATES DEVELOPMENT; NERVOUS-SYSTEM; TOUCH; SPECIFICATION; HYPERALGESIA AB VGLUT3-expressing unmyelinated low-threshold mechanoreceptors (C-LTMRs) are proposed to mediate pleasant touch and/or pain, but the molecular programs controlling C-LTMR development are unknown. Here, we performed genetic fate mapping, showing that VGLUT3 lineage sensory neurons are divided into two groups, based on transient or persistent VGLUT3 expression. VGLUT3-transient neurons are large-or medium-diameter myelinated mechanoreceptors that form the Merkel cell-neurite complex. VGLUT3-persistent neurons are small-diameter unmyelinated neurons that are further divided into two subtypes: (1) tyrosine hydroxylase (TH)-positive C-LTMRs that form the longitudinal lanceolate endings around hairs, and (2) TH-negative neurons that form epidermal-free nerve endings. We then found that VGLUT3-persistent neurons express the runt domain transcription factor Runx1. Analyses of mice with a conditional knock-out of Runx1 in VGLUT3 lineage neurons demonstrate that Runx1 is pivotal to the development of VGLUT3-persistent neurons, such as the expression of VGLUT3 and TH and the formation of the longitudinal lanceolate endings. Furthermore, Runx1 is required to establish mechanosensitivity in C-LTMRs, by controlling the expression of the mechanically gated ion channel Piezo2. Surprisingly, both acute and chronic mechanical pain was largely unaffected in these Runx1 mutants. These findings appear to argue against the recently proposed role of VGLUT3 in C-LTMRs in mediating mechanical hypersensitivity induced by nerve injury or inflammation. Thus, our studies provide new insight into the genetic program controlling C-LTMR development and call for a revisit for the physiological functions of C-LTMRs. C1 [Lou, Shan; Duan, Bo; Ma, Qiufu] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Lou, Shan; Duan, Bo; Ma, Qiufu] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Linh Vong; Lowell, Bradford B.] Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol, Boston, MA 02215 USA. [Linh Vong; Lowell, Bradford B.] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Ma, QF (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM Qiufu_Ma@dfci.harvard.edu RI Lou, Shan/C-1896-2013 OI Lou, Shan/0000-0002-1638-9917 FU NIH from NIDCR [R01 DE018025]; NINDS [P01 NS047572]; NIH from NIDDK [R01 DK075632]; Boston Nutrition Obesity Research Center Pilot and Feasibility [P30 DK046200] FX Work done in the Ma laboratory was supported by NIH grants from NIDCR (R01 DE018025) and NINDS (P01 NS047572), and work done in the Lowell laboratory was supported by the NIH grant from NIDDK (R01 DK075632). L. L. was supported by Boston Nutrition Obesity Research Center Pilot and Feasibility (P30 DK046200). We thank Dr. Nancy Speck and Dr. Gary Gilliland for the floxed Runx1 mice, Dr. David Corey for allowing us to use the recording setup in his laboratory, and Drs. Jing Hu and David Corey for advice on recording mechanically evoked currents on cultured DRG neurons. We thank Drs. Clifford Woolf, Oliver Holmes, and Fu-Chia Yang for helpful discussions and comments. NR 60 TC 45 Z9 46 U1 0 U2 15 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 16 PY 2013 VL 33 IS 3 BP 870 EP 882 DI 10.1523/JNEUROSCI.3942-12.2013 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 076KI UT WOS:000313955000004 PM 23325226 ER PT J AU Dorr, M Bex, PJ AF Dorr, Michael Bex, Peter J. TI Peri-Saccadic Natural Vision SO JOURNAL OF NEUROSCIENCE LA English DT Article ID EYE-MOVEMENTS; CONTRAST SENSITIVITY; VISUAL-PERCEPTION; MOTION PERCEPTION; PARIETAL CORTEX; SUPPRESSION; GRATINGS; SYSTEM; SPACE; TIME AB The fundamental role of the visual system is to guide behavior in natural environments. To optimize information transmission, many animals have evolved a non-homogeneous retina and serially sample visual scenes by saccadic eye movements. Such eye movements, however, introduce high-speed retinal motion and decouple external and internal reference frames. Until now, these processes have only been studied with unnatural stimuli, eye movement behavior, and tasks. These experiments confound retinotopic and geotopic coordinate systems and may probe a non-representative functional range. Here we develop a real-time, gaze-contingent display with precise spatiotemporal control over high-definition natural movies. In an active condition, human observers freely watched nature documentaries and indicated the location of periodic narrow-band contrast increments relative to their gaze position. In a passive condition under central fixation, the same retinal input was replayed to each observer by updating the video's screen position. Comparison of visual sensitivity between conditions revealed three mechanisms that the visual system has adapted to compensate for peri-saccadic vision changes. Under natural conditions we show that reduced visual sensitivity during eye movements can be explained simply by the high retinal speed during a saccade without recourse to an extra-retinal mechanism of active suppression; we give evidence for enhanced sensitivity immediately after an eye movement indicative of visual receptive fields remapping in anticipation of forthcoming spatial structure; and we demonstrate that perceptual decisions can be made in world rather than retinal coordinates. C1 [Dorr, Michael; Bex, Peter J.] Harvard Univ, Sch Med, Schepens Eye Res Inst, Massachusetts Eye & Ear Infirm,Dept Ophthalmol, Boston, MA 02114 USA. RP Dorr, M (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, Massachusetts Eye & Ear Infirm,Dept Ophthalmol, 20 Staniford St, Boston, MA 02114 USA. EM michael.dorr@schepens.harvard.edu; peter.bex@schepens.harvard.edu FU National Institutes of Health [EY018664, EY019281]; NVIDIA Academic Partnership FX This work was supported by National Institutes of Health Grants EY018664 and EY019281 and an NVIDIA Academic Partnership. NR 47 TC 16 Z9 17 U1 0 U2 28 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 16 PY 2013 VL 33 IS 3 BP 1211 EP 1217 DI 10.1523/JNEUROSCI.4344-12.2013 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 076KI UT WOS:000313955000035 PM 23325257 ER PT J AU Zhang, SL Zhang, N Blain, JC Szostak, JW AF Zhang, Shenglong Zhang, Na Blain, J. Craig Szostak, Jack W. TI Synthesis of N3 '-P5 '-linked Phosphoramidate DNA by Nonenzymatic Template-Directed Primer Extension SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID ALTERNATIVE GENETIC SYSTEM; NUCLEIC-ACID; ACTIVATED RIBONUCLEOTIDES; RNA; OLIGOMERIZATION; ANALOGS; MODEL; OLIGONUCLEOTIDES; POLYMERIZATION; REPLICATION AB A fast and accurate pathway for nonenzymatic RNA replication would simplify models for the emergence of the RNA world from the prebiotic chemistry of the early earth. However, numerous difficulties stand in the way of an experimental demonstration of effective nonenzymatic RNA replication. To gain insight into the necessary properties of potentially self-replicating informational polymers, we have studied several model systems based on amino-sugar nucleotides. Here we describe the synthesis of N3'-P5'-linked phosphoramidate DNA (3'-NP-DNA) by the template-directed polymerization of activated 3'-amino-2',3'-dideoxyribonucleotides. 3'-NP-DNA is an interesting model because of its very RNA-like A-type duplex conformation and because activated 3'-amino-2',3'-dideozyribonucleotides are much more reactive than the corresponding activated ribonucleotides. In contrast to our previous studies with 2'-amino-2',3'-dideoxyribonucleotides (for which G and C but not A and T exhibit efficient template copying), we have found that all four canonical 3'-amino-2',3'-dideoxyribonucleotides (G, C, A, and T) polymerize efficiently on RNA templates. RNA templates are generally superior to DNA templates, and oligo-ribo-T templates are superior to oligo-ribo-U templates, which are the least efficient of the RNA homopolymer templates. We have also found that activation of 3'-aminonucleotides with 2-methylimidazole results in a ca. 10-fold higher polymerization rate relative to activation with imidazole, an observation that parallels earlier findings with ribonucleotides. We discuss the implications of our experiments for the possibility of self-replication in the 3'-NP-DNA and RNA systems. C1 [Szostak, Jack W.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, 185 Cambridge St, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu FU NSF [CHE-0809413] FX We are grateful to the members of our laboratory for helpful discussions and comments on the manuscript. This research was funded in part by Grant CHE-0809413 from the NSF. J.W.S. is an Investigator of the Howard Hughes Medical Institute. NR 36 TC 13 Z9 14 U1 2 U2 60 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JAN 16 PY 2013 VL 135 IS 2 BP 924 EP 932 DI 10.1021/ja311164j PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA 075XP UT WOS:000313920800065 PM 23252395 ER PT J AU Prasad, V Jena, AB AF Prasad, Vinay Jena, Anupam B. TI Prespecified Falsification End Points Can They Validate True Observational Associations? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID FRACTURES; RISK C1 [Prasad, Vinay] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Jena, Anupam B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Jena, Anupam B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jena, Anupam B.] Natl Bur Econ Res, Cambridge, MA 02138 USA. RP Jena, AB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM jena@hcp.med.harvard.edu NR 8 TC 48 Z9 48 U1 0 U2 4 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 16 PY 2013 VL 309 IS 3 BP 241 EP 242 DI 10.1001/jama.2012.96867 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 070XG UT WOS:000313546800021 PM 23321761 ER PT J AU Hasegawa, K Hiraide, A Chang, YC Brown, DFM AF Hasegawa, Kohei Hiraide, Atsushi Chang, Yuchiao Brown, David F. M. TI Association of Prehospital Advanced Airway Management With Neurologic Outcome and Survival in Patients With Out-of-Hospital Cardiac Arrest SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID AMERICAN-HEART-ASSOCIATION; EUROPEAN-RESUSCITATION-COUNCIL; HEALTH-CARE PROFESSIONALS; ENDOTRACHEAL INTUBATION; CARDIOPULMONARY-RESUSCITATION; LIFE-SUPPORT; TASK-FORCE; RECOMMENDED GUIDELINES; STROKE-FOUNDATION; UTSTEIN STYLE AB Importance It is unclear whether advanced airway management such as endotracheal intubation or use of supraglottic airway devices in the prehospital setting improves outcomes following out-of-hospital cardiac arrest (OHCA) compared with conventional bag-valve-mask ventilation. Objective To test the hypothesis that prehospital advanced airway management is associated with favorable outcome after adult OHCA. Design, Setting, and Participants Prospective, nationwide, population-based study (All-Japan Utstein Registry) involving 649 654 consecutive adult patients in Japan who had an OHCA and in whom resuscitation was attempted by emergency responders with subsequent transport to medical institutions from January 2005 through December 2010. Main Outcome Measures Favorable neurological outcome 1 month after an OHCA, defined as cerebral performance category 1 or 2. Results Of the eligible 649 359 patients with OHCA, 367 837 (57%) underwent bag-valve-mask ventilation and 281 522 (43%) advanced airway management, including 41 972 (6%) with endotracheal intubation and 239 550 (37%) with use of supraglottic airways. In the full cohort, the advanced airway group incurred a lower rate of favorable neurological outcome compared with the bag-valve-mask group (1.1% vs 2.9%; odds ratio [OR], 0.38; 95% CI, 0.36-0.39). In multivariable logistic regression, advanced airway management had an OR for favorable neurological outcome of 0.38 (95% CI, 0.37-0.40) after adjusting for age, sex, etiology of arrest, first documented rhythm, witnessed status, type of bystander cardiopulmonary resuscitation, use of public access automated external defibrillator, epinephrine administration, and time intervals. Similarly, the odds of neurologically favorable survival were significantly lower both for endotracheal intubation (adjusted OR, 0.41; 95% CI, 0.37-0.45) and for supraglottic airways (adjusted OR, 0.38; 95% CI, 0.36-0.40). In a propensity score-matched cohort (357 228 patients), the adjusted odds of neurologically favorable survival were significantly lower both for endotracheal intubation (adjusted OR, 0.45; 95% CI, 0.37-0.55) and for use of supraglottic airways (adjusted OR, 0.36; 95% CI, 0.33-0.39). Both endotracheal intubation and use of supraglottic airways were similarly associated with decreased odds of neurologically favorable survival. Conclusion and Relevance Among adult patients with OHCA, any type of advanced airway management was independently associated with decreased odds of neurologically favorable survival compared with conventional bag-valve-mask ventilation. JAMA. 2013;309(3):257-266 www.jama.com C1 [Hasegawa, Kohei] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Hasegawa, Kohei; Brown, David F. M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Hiraide, Atsushi] Kinki Univ, Fac Med, Dept Acute Med, Osaka, Japan. RP Hasegawa, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, 326 Cambridge St,Ste 410, Boston, MA 02114 USA. EM khasegawa1@partners.org FU Fire and Disaster Management Agency FX This study was supported by a grant to Dr Hiraide for emergency management scientific research from the Fire and Disaster Management Agency. NR 40 TC 118 Z9 122 U1 2 U2 27 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 16 PY 2013 VL 309 IS 3 BP 257 EP 266 DI 10.1001/jama.2012.187612 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 070XG UT WOS:000313546800026 PM 23321764 ER PT J AU Bai, X Trowbridge, JJ Riley, E Lee, JA DiBiase, A Kaartinen, VM Orkin, SH Zon, LI AF Bai, Xiaoying Trowbridge, Jennifer J. Riley, Elizabeth Lee, Joseph A. DiBiase, Anthony Kaartinen, Vesa M. Orkin, Stuart H. Zon, Leonard I. TI TiF1-gamma plays an essential role in murine hematopoiesis and regulates transcriptional elongation of erythroid genes SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Hematopoiesis; Lineage differentiation; Transcription elongation ID CHRONIC MYELOMONOCYTIC LEUKEMIA; RNA-POLYMERASE; P-TEFB; TUMOR-SUPPRESSOR; ACTIVATION; DROSOPHILA; PROMOTER; PATHWAY; FAMILY; FETAL AB Transcriptional regulators play critical roles in the regulation of cell fate during hematopoiesis. Previous studies in zebrafish have identified an essential role for the transcriptional intermediary factor TIF1 gamma in erythropoiesis by regulating the transcription elongation of erythroid genes. To study if TIF1 gamma plays a similar role in murine erythropoiesis and to assess its function in other blood lineages, we generated mouse models with hematopoietic deletion of TIF1 gamma. Our results showed a block in erythroid maturation in the bone marrow following tif1 gamma deletion that was compensated with enhanced spleen erythropoiesis. Further analyses revealed a defect in transcription elongation of erythroid genes in the bone marrow. In addition, loss of TIF1 gamma resulted in defects in other blood compartments, including a profound loss of B cells, a dramatic expansion of granulocytes and decreased HSC function. TIF1 gamma exerts its functions in a cell-autonomous manner as revealed by competitive transplantation experiments. Our study therefore demonstrates that TIF1 gamma plays essential roles in multiple murine blood lineages and that its function in transcription elongation is evolutionally conserved. Published by Elsevier Inc. C1 [Bai, Xiaoying; Riley, Elizabeth; Lee, Joseph A.; DiBiase, Anthony; Zon, Leonard I.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Bai, Xiaoying; Trowbridge, Jennifer J.; Riley, Elizabeth; Lee, Joseph A.; DiBiase, Anthony; Orkin, Stuart H.; Zon, Leonard I.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Orkin, Stuart H.; Zon, Leonard I.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Trowbridge, Jennifer J.; Orkin, Stuart H.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Orkin, Stuart H.; Zon, Leonard I.] Univ Michigan, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA. [Kaartinen, Vesa M.] Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA. RP Zon, LI (reprint author), Childrens Hosp, Stem Cell Program, Karp Bldg,7th Floor, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu OI Kaartinen, Vesa/0000-0002-9432-510X FU NIH/NIDDK [K99DK088963]; Leukemia and Lymphoma Society; Children's Leukemia Research Foundation; ASH Scholar award; NIH [PO1HL32262] FX We would like to thank Ronald Mathieu for flow cytometry assistance. X.B. was supported by the NIH/NIDDK Grant K99DK088963. J.J.T. was supported by fellowships from the Leukemia and Lymphoma Society, the Children's Leukemia Research Foundation, and ASH Scholar award. This work was supported by the NIH Grant PO1HL32262. S.H.O. and L.I.Z. are Investigators of the HHMI. NR 29 TC 13 Z9 13 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JAN 15 PY 2013 VL 373 IS 2 BP 422 EP 430 DI 10.1016/j.ydbio.2012.10.008 PG 9 WC Developmental Biology SC Developmental Biology GA 068QL UT WOS:000313381200017 PM 23159334 ER PT J AU Roxburgh, RH Smith, CO Lim, JG Bachman, DF Byrd, E Bird, TD AF Roxburgh, Richard H. Smith, Corrie O. Lim, Jung G. Bachman, David F. Byrd, Erica Bird, Thomas D. TI The unique co-occurrence of spinocerebellar ataxia type 10 (SCA10) and Huntington disease SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE Spinocerebellar ataxia; Huntington disease; Trinucleotide repeat; Neurogenetics ID ATTCT REPEAT EXPANSION; BRAZILIAN FAMILIES; PHENOTYPE; GENE; HOMOZYGOSITY; MUTATIONS; ORIGIN; ONSET; SIGNS AB We present a unique thirty-nine year old woman with both Huntington's disease (HD) and spinocerebellar ataxia type 10 (SCA10). She has 48 CAG repeats in the HD gene and 2511 ATTCT repeats in the ATX10 gene. Although both conditions are repeat expansion diseases they are thought to have quite different pathogenic mechanisms. The symptomatic age of onset in this patient (mid30s) is within the expected range for her repeat expansion sizes for each condition, but we discuss the evidence that the two conditions may interact to produce a more severe cognitive phenotype than would be expected for either of the conditions independently. The subject has Amerindian background on the maternal side from Colombia, South America, thus adding a 5th country expressing SCA10, all with Amerindian ancestry. (C) 2012 Elsevier B.V. All rights reserved. C1 [Roxburgh, Richard H.] Auckland City Hosp, Dept Neurol, Auckland, New Zealand. [Roxburgh, Richard H.] Univ Auckland, Ctr Brain Res, Auckland 1, New Zealand. [Smith, Corrie O.; Byrd, Erica; Bird, Thomas D.] Univ Washington, Dept Med Med Genet & Neurol, Seattle, WA 98195 USA. [Lim, Jung G.] Lourdes Med Ctr, Pasco, WA 99301 USA. [Bird, Thomas D.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. RP Bird, TD (reprint author), Univ Washington, Box 356465, Seattle, WA 98195 USA. EM tomnroz@uw.edu OI Roxburgh, Richard/0000-0002-8930-7003 FU Athena Diagnostics, Inc. FX TDB receives licensing fees from Athena Diagnostics, Inc. NR 21 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD JAN 15 PY 2013 VL 324 IS 1-2 BP 176 EP 178 DI 10.1016/j.jns.2012.09.030 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 088RT UT WOS:000314855500035 PM 23083689 ER PT J AU Hariri, LP Villiger, M Applegate, MB Mino-Kenudson, M Mark, EJ Bouma, BE Suter, MJ AF Hariri, Lida P. Villiger, Martin Applegate, Matthew B. Mino-Kenudson, Mari Mark, Eugene J. Bouma, Brett E. Suter, Melissa J. TI Seeing beyond the Bronchoscope to Increase the Diagnostic Yield of Bronchoscopic Biopsy SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID OPTICAL COHERENCE TOMOGRAPHY; CELL LUNG-CANCER; GUIDELINES 2ND EDITION; IN-VIVO; COMPUTED-TOMOGRAPHY; BRONCHIAL LESIONS; PULMONARY NODULES; LIGHT-MICROSCOPY; COLLAGEN; NEEDLE C1 [Hariri, Lida P.; Mino-Kenudson, Mari; Mark, Eugene J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hariri, Lida P.; Villiger, Martin; Applegate, Matthew B.; Bouma, Brett E.; Suter, Melissa J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Applegate, Matthew B.; Suter, Melissa J.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Hariri, Lida P.; Villiger, Martin; Mino-Kenudson, Mari; Mark, Eugene J.; Bouma, Brett E.; Suter, Melissa J.] Harvard Univ, Sch Med, Boston, MA USA. RP Suter, MJ (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 55 Fruit St,Warren Bldg,Room 407, Boston, MA 02114 USA. EM msuter@partners.org FU NCI NIH HHS [R00 CA134920, R00CA134920]; NIBIB NIH HHS [P41 EB015903, P41EB01590] NR 50 TC 11 Z9 11 U1 0 U2 10 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN 15 PY 2013 VL 187 IS 2 BP 125 EP 129 DI 10.1164/rccm.201208-1483OE PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 075YY UT WOS:000313924600007 PM 23322794 ER PT J AU Kartalija, M Ovrutsky, AR Bryan, CL Pott, GB Fantuzzi, G Thomas, J Strand, MJ Bai, XY Ramamoorthy, P Rothman, MS Nagabhushanam, V McDermott, M Levin, AR Frazer-Abel, A Giclas, PC Korner, J Iseman, MD Shapiro, L Chan, ED AF Kartalija, Marinka Ovrutsky, Alida R. Bryan, Courtney L. Pott, Gregory B. Fantuzzi, Giamila Thomas, Jacob Strand, Matthew J. Bai, Xiyuan Ramamoorthy, Preveen Rothman, Micol S. Nagabhushanam, Vijaya McDermott, Michael Levin, Adrah R. Frazer-Abel, Ashley Giclas, Patricia C. Korner, Judith Iseman, Michael D. Shapiro, Leland Chan, Edward D. TI Patients with Nontuberculous Mycobacterial Lung Disease Exhibit Unique Body and Immune Phenotypes SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE leptin; adiponectin; pectus excavatum; scoliosis; Marfan syndrome ID COMPLEX PULMONARY-DISEASE; NECROSIS-FACTOR-ALPHA; GROWTH-FACTOR-BETA; AVIUM COMPLEX; INTERFERON-GAMMA; MARFAN-SYNDROME; LEPTIN CONCENTRATIONS; CYTOKINE PRODUCTION; PECTUS EXCAVATUM; TGF-BETA AB Rationale: Among patients with nontuberculous mycobacterial lung disease is a subset of previously healthy women with a slender body morphotype, often with scoliosis and/or pectus excavatum. We hypothesize that unidentified factors predispose these individuals to pulmonary nontuberculous mycobacterial disease. Objectives: To compare body morphotype, serum adipokine levels, and whole-blood cytokine responses of patients with pulmonary nontuberculous mycobacteria (pNTM) with contemporary control subjects who are well matched demographically. Methods: We enrolled 103 patients with pNTM and 101 uninfected control subjects of similar demographics. Body mass index and body fat were quantified. All patients with pNTM and a subset of control subjects were evaluated for scoliosis and pectus excavatum. Serum leptin and adiponectin were measured. Specific cytokines important to host-defense against mycobacteria were measured in whole blood before and after stimulation. Measurements and Main Results: Patients with pNTM and control subjects were well matched for age, gender, and race. Patients with pNTM had significantly lower body mass index and body fat and were significantly taller than control subjects. Scoliosis and pectus excavatum were significantly more prevalent in patients with pNTM. The normal relationships between the adipokines and body fat were lost in the patients with pNTM, a novel finding. IFN-gamma and IL-10 levels were significantly suppressed in stimulated whole blood of patients with pNTM. Conclusions: This is the first study to comprehensively compare body morphotype, adipokines, and cytokine responses between patients with NTM lung disease and demographically matched controls. Our findings suggest a novel, predisposing immunophenotype that should be mechanistically defined. C1 [Kartalija, Marinka; Bryan, Courtney L.; Pott, Gregory B.; Iseman, Michael D.; Shapiro, Leland] Univ Colorado Denver, Div Infect Dis, Aurora, CO USA. [Thomas, Jacob; Strand, Matthew J.] Univ Colorado Denver, Dept Biostat, Aurora, CO USA. [Bai, Xiyuan; Iseman, Michael D.; Chan, Edward D.] Univ Colorado Denver, Div Pulm Sci & Crit Care Med, Aurora, CO USA. [Rothman, Micol S.; McDermott, Michael] Univ Colorado Denver, Div Endocrinol, Aurora, CO USA. [Ovrutsky, Alida R.; Bai, Xiyuan; Ramamoorthy, Preveen; Nagabhushanam, Vijaya; Levin, Adrah R.; Iseman, Michael D.; Chan, Edward D.] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA. [Ovrutsky, Alida R.; Bai, Xiyuan; Ramamoorthy, Preveen; Nagabhushanam, Vijaya; Levin, Adrah R.; Iseman, Michael D.; Chan, Edward D.] Natl Jewish Hlth, Dept Acad Affairs, Denver, CO 80206 USA. [Strand, Matthew J.] Natl Jewish Hlth, Div Biostat, Denver, CO 80206 USA. [Frazer-Abel, Ashley; Giclas, Patricia C.] Natl Jewish Hlth, Complement Lab, Denver, CO 80206 USA. [Bryan, Courtney L.; Pott, Gregory B.; Shapiro, Leland; Chan, Edward D.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Fantuzzi, Giamila] Univ Illinois, Dept Kinesiol & Nutr, Chicago, IL USA. [Korner, Judith] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. RP Chan, ED (reprint author), Natl Jewish Hlth, Dept Med, D509,Neustadt Bldg,1400 Jackson St, Denver, CO 80206 USA. EM chane@njhealth.org RI Fantuzzi, Giamila/A-1758-2009 OI Fantuzzi, Giamila/0000-0001-5334-0082 FU Fern and Phil Leitman of Non-tuberculous Mycobacteria Info and Research (NTMir) of Miami, Florida; National Institutes of Health/National Center for Research Resources Colorado CTSI [UL1 RR025780]; Denver Veterans Affairs Medical Center FX This work was supported by Fern and Phil Leitman of Non-tuberculous Mycobacteria Info and Research (NTMir) of Miami, Florida and by National Institutes of Health/National Center for Research Resources Colorado CTSI grant no. UL1 RR025780.; The authors thank Dr. Leonid Heifets for providing the M. intracellulare isolate used in the ex vivo experiments, Eric Schonteich for help with some of the assays, and Dr. Mary Bessesen for providing Dr. Kartalija with a Training Grant from the Denver Veterans Affairs Medical Center. NR 63 TC 53 Z9 53 U1 1 U2 7 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. PD JAN 15 PY 2013 VL 187 IS 2 BP 197 EP 205 DI 10.1164/rccm.201206-1035OC PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 075YY UT WOS:000313924600016 PM 23144328 ER PT J AU Walensky, RP Sax, PE Nakamura, YM Weinstein, MC Pei, PP Freedberg, KA Paltiel, AD Schackman, BR AF Walensky, Rochelle P. Sax, Paul E. Nakamura, Yoriko M. Weinstein, Milton C. Pei, Pamela P. Freedberg, Kenneth A. Paltiel, A. David Schackman, Bruce R. TI Economic Savings Versus Health Losses: The Cost-Effectiveness of Generic Antiretroviral Therapy in the United States SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID TENOFOVIR-CONTAINING REGIMENS; RANDOMIZED CONTROLLED-TRIAL; TREATMENT-NAIVE PATIENTS; HIV-1 INFECTION; COMBINATION THERAPY; DOUBLE-BLIND; EFFICACY; EMTRICITABINE; VIRUS; CARE AB Background: U. S. HIV treatment guidelines recommend branded once-daily, 1-pill efavirenz-emtricitabine-tenofovir as first-line antiretroviral therapy (ART). With the anticipated approval of generic efavirenz in the United States, a once-daily, 3-pill alternative (generic efavirenz, generic lamivudine, and tenofovir) will decrease cost but may reduce adherence and virologic suppression. Objective: To assess the clinical effect, costs, and cost-effectiveness of a 3-pill, generic-based regimen compared with a branded, co-formulated regimen and to project the potential national savings in the first year of a switch to generic-based ART. Design: Mathematical simulation of HIV disease. Setting: United States. Patients: HIV-infected persons. Intervention: No ART (for comparison); 3-pill, generic-based ART; and branded ART. Measurements: Quality-adjusted life expectancy, costs, and incremental cost-effectiveness ratios (ICERs) in dollars per qualityadjusted life-year (QALY). Results: Compared with no ART, generic-based ART has an ICER of $ 21 100/QALY. Compared with generic-based ART, branded ART increases lifetime costs by $ 42 500 and per-person survival gains by 0.37 QALYs for an ICER of $ 114 800/QALY. Estimated first-year savings, if all eligible U. S. patients start or switch to generic-based ART, are $ 920 million. Most plausible assumptions about generic-based ART efficacy and costs lead to branded ART ICERs greater than $ 100 000/QALY. Limitation: The efficacy and price reduction associated with generic drugs are unknown, and estimates are intended to be conservative. Conclusion: Compared with a slightly less effective generic-based regimen, the cost-effectiveness of first-line branded ART exceeds $ 100 000/QALY. Generic-based ART in the United States could yield substantial budgetary savings to HIV programs. C1 [Walensky, Rochelle P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Brigham & Womens Hosp, Div Infect Dis,Med Practice Evaluat Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02114 USA. Yale Univ, Sch Med, New Haven, CT USA. Weill Cornell Med Coll, New York, NY USA. RP Walensky, RP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Brigham & Womens Hosp, Div Infect Dis,Med Practice Evaluat Ctr, 50 Staniford St,9th Floor, Boston, MA 02114 USA. OI Walensky, Rochelle P./0000-0002-8795-379X FU National Institute of Allergy and Infectious Diseases [R37-AI42006, R01-AI093269] FX By grants R37-AI42006 and R01-AI093269 from the National Institute of Allergy and Infectious Diseases. NR 60 TC 58 Z9 58 U1 1 U2 16 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 15 PY 2013 VL 158 IS 2 BP 84 EP + DI 10.7326/0003-4819-158-2-201301150-00002 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 077LO UT WOS:000314029400014 PM 23318310 ER PT J AU Passarelli, MN Phipps, AI Potter, JD Makar, KW Coghill, AE Wernli, KJ White, E Chan, AT Hutter, CM Peters, U Newcomb, PA AF Passarelli, Michael N. Phipps, Amanda I. Potter, John D. Makar, Karen W. Coghill, Anna E. Wernli, Karen J. White, Emily Chan, Andrew T. Hutter, Carolyn M. Peters, Ulrike Newcomb, Polly A. TI Common Single-Nucleotide Polymorphisms in the Estrogen Receptor beta Promoter Are Associated with Colorectal Cancer Survival in Postmenopausal Women SO CANCER RESEARCH LA English DT Article ID HORMONE REPLACEMENT THERAPY; INITIATIVE CLINICAL-TRIAL; COLON-CANCER; ER-BETA; PLUS PROGESTIN; ISOFORM EXPRESSION; PROSTATE-CANCER; BREAST-CANCER; LIFE-STYLE; ESR2 GENE AB Loss of estrogen receptor b (ER beta) expression in the gut is associated with colorectal cancer (CRC) initiation and progression. Germline single-nucleotide polymorphisms (SNP) in genes for the sex-steroid hormone receptors are not strongly associated with CRC risk; however, these SNPs have not previously been evaluated in relation to survival after diagnosis. We enrolled 729 women, ages 50 to 74, diagnosed with invasive CRC between 1997 and 2002 in 13 counties covered by the Seattle-Puget Sound Surveillance Epidemiology and End Results cancer registry. Participants provided germline DNA. We selected 99 tag-SNPs for the androgen receptor (AR), ER alpha (ESR1), ER beta (ESR2), and progesterone receptor (PGR) genes. Mortality outcomes were ascertained from the National Death Index. During a median of 6.6 years of follow-up, 244 deaths occurred (161 from CRC). We identified 20 SNPs (12 of ESR2 and 8 of PGR) for replication in 1,729 women diagnosed with incident invasive CRC (555 deaths; 405 from CRC) from three prospective cohort studies that participate in the Genetics and Epidemiology of Colorectal Cancer Consortium. Three correlated SNPs in the promoter of ESR2 (rs2987983, rs3020443, and rs2978381) were statistically significant predictors of CRC-specific and overall survival. Minor alleles of each were associated with improved survival [for rs2987983, CRC-specific HR, 0.77; 95% confidence interval (CI), 0.60-0.99 in the initial study, and HR, 0.79; CI, 0.64-0.98 in replication]. No associations were noted for SNPs of AR, ESR1, or PGR. SNPs in the promoter of ESR2 may be important to pathways related to the association between ERb and tumor progression and metastasis. Cancer Res; 73(2); 767-75. (C) 2012 AACR. C1 [Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Passarelli, Michael N.; Potter, John D.; Coghill, Anna E.; White, Emily; Hutter, Carolyn M.; Peters, Ulrike; Newcomb, Polly A.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. [Wernli, Karen J.] Grp Hlth Res Inst, Seattle, WA USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA. [Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. RP Newcomb, PA (reprint author), Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Div Publ Hlth Sci, 1100 Fairview Ave N,M4-B402, Seattle, WA 98109 USA. EM pnewcomb@fhcrc.org OI Potter, John/0000-0001-5439-1500 FU NCI/NIH/HHS [U24-CA074794, R01-CA076366, U01-CA137088, P01-CA087969, R01-CA137178, K05-CA154337, R01-CA059045, T32-CA009168, R25-CA094880]; NHLBI/NIH/HHS [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C] FX PMH-CCFR is supported by NCI/NIH/HHS (U24-CA074794 and R01-CA076366 to P.A. Newcomb). GECCO is supported by NCI/NIH/HHS (U01-CA137088 to U. Peters). NHS is supported by NCI/NIH/HHS (P01-CA087969 and R01-CA137178 to A.T. Chan). VITAL is supported in part by NCI/NIH/HHS (K05-CA154337 to E. White). The WHI program is funded by NHLBI/NIH/HHS through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. Funding for the genome-wide scan of WHI was provided by NCI/NIH/HHS (R01-CA059045 to U. Peters). Three authors were supported by training grants from NCI/NIH/HHS (T32-CA009168 to M.N. Passarelli and A.E. Coghill, and R25-CA094880 to A.I. Phipps.) NR 50 TC 13 Z9 13 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2013 VL 73 IS 2 BP 767 EP 775 DI 10.1158/0008-5472.CAN-12-2484 PG 9 WC Oncology SC Oncology GA 073JO UT WOS:000313739500035 PM 23149914 ER PT J AU Cortot, AB Repellin, CE Shimamura, T Capelletti, M Zejnullahu, K Ercan, D Christensen, JG Wong, KK Gray, NS Janne, PA AF Cortot, Alexis B. Repellin, Claire E. Shimamura, Takeshi Capelletti, Marzia Zejnullahu, Kreshnik Ercan, Dalia Christensen, James G. Wong, Kwok-Kin Gray, Nathanael S. Jaenne, Pasi A. TI Resistance to Irreversible EGF Receptor Tyrosine Kinase Inhibitors through a Multistep Mechanism Involving the IGF1R Pathway SO CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; FACTOR-I RECEPTOR; ACQUIRED-RESISTANCE; T790M MUTATION; 1ST-LINE TREATMENT; OPEN-LABEL; PHASE-II; GEFITINIB; ERLOTINIB; TUMORS AB The clinical efficacy of EGF receptor (EGFR) kinase inhibitors gefitinib and erlotinib is limited by the development of drug resistance. The most common mechanism of drug resistance is the secondary EGFR T790M mutation. Strategies to overcome EGFR T790M-mediated drug resistance include the use of mutant selective EGFR inhibitors, including WZ4002, or the use of high concentrations of irreversible quinazoline EGFR inhibitors such as PF299804. In the current study, we develop drug-resistant versions of the EGFR-mutant PC9 cell line, which reproducibly develops EGFR T790M as a mechanism of drug resistance to gefitinib. Neither PF299804-resistant nor WZ4002-resistant clones of PC9 harbor EGFR T790M. Instead, they have shown activated insulin-like growth factor receptor (IGF1R) signaling as a result of loss of expression of IGFBP3 with the IGF1R inhibitor, BMS 536924, restoring EGFR inhibitor sensitivity. Intriguingly, prolonged exposure to either PF299804 or WZ4002 results in the emergence of a more drug-resistant subclone that exhibits ERK activation. AMEK inhibitor, CI-1040, partially restores sensitivity to the EGFR/IGF1R inhibitor combination. Moreover, an IGF1R or MEK inhibitor used in combination with either PF299804 or WZ4002 completely prevents the emergence of drug-resistant clones in this model system. Our studies suggest that more effectivemeans of inhibiting EGFR T790Mwill prevent the emergence of this common drug resistance mechanism in EGFR-mutant non-small cell lung cancer. However, multiple drug resistance mechanisms can still emerge. Preventing the emergence of drug resistance, by targeting pathways that become activated in resistant cancers, may be a more effective clinical strategy. Cancer Res; 73(2); 834-43. (C) 2012 AACR. C1 [Cortot, Alexis B.; Repellin, Claire E.; Capelletti, Marzia; Zejnullahu, Kreshnik; Ercan, Dalia; Wong, Kwok-Kin; Jaenne, Pasi A.] Brigham & Womens Hosp, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02215 USA. [Cortot, Alexis B.; Repellin, Claire E.; Shimamura, Takeshi; Capelletti, Marzia; Zejnullahu, Kreshnik; Ercan, Dalia; Wong, Kwok-Kin; Jaenne, Pasi A.] Brigham & Womens Hosp, Dept Med Oncol, Boston, MA 02215 USA. [Shimamura, Takeshi; Wong, Kwok-Kin; Jaenne, Pasi A.] Brigham & Womens Hosp, Belfer Inst Appl Canc Sci, Boston, MA 02215 USA. [Gray, Nathanael S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Gray, Nathanael S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02215 USA. [Wong, Kwok-Kin; Jaenne, Pasi A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. [Wong, Kwok-Kin; Jaenne, Pasi A.] Harvard Univ, Sch Med, Boston, MA USA. [Christensen, James G.] Pfizer Global Res & Dev, Dept Res Pharmacol, La Jolla, CA USA. RP Janne, PA (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, HIM223,450 Brookline Ave, Boston, MA 02215 USA. EM pjanne@partners.org OI wong, kwok kin/0000-0001-6323-235X FU National Institutes of Health [RO1CA114465, R01CA135257]; National Cancer Institute Lung [SPORE P50CA090578]; College des Enseignants de Pneumologie; Fondation de France FX This study is supported by grants from the National Institutes of Health RO1CA114465 (P.A. Janne), R01CA135257 (P.A. Janne), the National Cancer Institute Lung SPORE P50CA090578 (P.A. Janne and K.- K. Wong), the College des Enseignants de Pneumologie (A.B. Cortot), and the Fondation de France (A.B. Cortot). NR 37 TC 81 Z9 83 U1 1 U2 21 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2013 VL 73 IS 2 BP 834 EP 843 DI 10.1158/0008-5472.CAN-12-2066 PG 10 WC Oncology SC Oncology GA 073JO UT WOS:000313739500042 PM 23172312 ER PT J AU Liu, CW Peng, WY Xu, CY Lou, YY Zhang, MY Wargo, JA Chen, JQ Li, HYS Watowich, SS Yang, Y Frederick, DT Cooper, ZA Mbofung, RM Whittington, M Flaherty, KT Woodman, SE Davies, MA Radvanyi, LG Overwijk, WW Lizee, G Hwu, P AF Liu, Chengwen Peng, Weiyi Xu, Chunyu Lou, Yanyan Zhang, Minying Wargo, Jennifer A. Chen, Jie Qing Li, Haiyan S. Watowich, Stephanie S. Yang, Yan Frederick, Dennie Tompers Cooper, Zachary A. Mbofung, Rina M. Whittington, Mayra Flaherty, Keith T. Woodman, Scott E. Davies, Michael A. Radvanyi, Laszlo G. Overwijk, Willem W. Lizee, Gregory Hwu, Patrick TI BRAF Inhibition Increases Tumor Infiltration by T cells and Enhances the Antitumor Activity of Adoptive Immunotherapy in Mice SO CLINICAL CANCER RESEARCH LA English DT Article ID SIGNALING PATHWAY; MELANOMA-CELLS; METASTATIC MELANOMA; DENDRITIC CELLS; RAF KINASE; IN-VIVO; B-RAF; CANCER; THERAPY; RESISTANCE AB Purpose: Treatment of melanoma patients with selective BRAF inhibitors results in objective clinical responses in the majority of patients with BRAF-mutant tumors. However, resistance to these inhibitors develops within a few months. In this study, we test the hypothesis that BRAF inhibition in combination with adoptive T-cell transfer (ACT) will be more effective at inducing long-term clinical regressions of BRAF-mutant tumors. Experimental Design: BRAF-mutated human melanoma tumor cell lines transduced to express gp100 and H-2D(b) to allow recognition by gp100-specific pmel-1 T cells were used as xenograft models to assess melanocyte differentiation antigen-independent enhancement of immune responses by BRAF inhibitor PLX4720. Luciferase-expressing pmel-1 T cells were generated to monitor T-cell migration in vivo. The expression of VEGF was determined by ELISA, protein array, and immunohistochemistry. Importantly, VEGF expression after BRAF inhibition was tested in a set of patient samples. Results: We found that administration of PLX4720 significantly increased tumor infiltration of adoptively transferred T cells in vivo and enhanced the antitumor activity of ACT. This increased T-cell infiltration was primarily mediated by the ability of PLX4720 to inhibit melanoma tumor cell production of VEGF by reducing the binding of c-myc to the VEGF promoter. Furthermore, analysis of human melanoma patient tumor biopsies before and during BRAF inhibitor treatment showed downregulation of VEGF consistent with the preclinical murine model. Conclusion: These findings provide a strong rationale to evaluate the potential clinical application of combining BRAF inhibition with T-cell-based immunotherapy for the treatment of patients with melanoma. Clin Cancer Res; 19(2); 393-403. (C)2012 AACR. C1 [Liu, Chengwen; Peng, Weiyi; Xu, Chunyu; Lou, Yanyan; Zhang, Minying; Chen, Jie Qing; Yang, Yan; Mbofung, Rina M.; Whittington, Mayra; Woodman, Scott E.; Davies, Michael A.; Radvanyi, Laszlo G.; Overwijk, Willem W.; Lizee, Gregory; Hwu, Patrick] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA. [Li, Haiyan S.; Watowich, Stephanie S.] Univ Texas MD Anderson Canc Ctr, Ctr Canc Immunol Res, Dept Immunol, Houston, TX 77030 USA. [Davies, Michael A.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Div Canc Med, Houston, TX 77030 USA. [Wargo, Jennifer A.; Frederick, Dennie Tompers; Cooper, Zachary A.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Flaherty, Keith T.] Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. RP Hwu, P (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM phwu@mdanderson.org OI Mbofung, Rina/0000-0003-3872-3143; Watowich, Stephanie/0000-0003-1969-659X; Cooper, Zachary/0000-0003-1059-0940 FU National Cancer Institute [R01 CA123182, R01 CA116206, R01 CA143077]; Cancer Prevention Research Institute of Texas [RP110248]; Jurgen Sager & Transocean Melanoma Research Fund; El Paso Foundation for Melanoma Research; Miriam and Jim Mulva Melanoma Research Fund; Gillson Logenbaugh Foundation; Adelson Medical Research Foundation; GlaxoSmithKline; Genentech/Roche; AstraZeneca FX This work was supported in part by the following National Cancer Institute grants: R01 CA123182, R01 CA116206, and R01 CA143077. This research was also supported in part by Cancer Prevention Research Institute of Texas grant RP110248, Jurgen Sager & Transocean Melanoma Research Fund, El Paso Foundation for Melanoma Research, Miriam and Jim Mulva Melanoma Research Fund, the Gillson Logenbaugh Foundation, and Adelson Medical Research Foundation.; K.T. Flaherty is a consultant/advisory board member of Roche/Genentech, GlaxoSmithKline, and Novartis. M.A. Davies has a commercial research grant from GlaxoSmithKline, Genentech/Roche, and AstraZeneca, and is a consultant/advisory board member of GlaxoSmithKline, Genentech, and Novartis. No potential conflicts of interest were disclosed by the other authors. NR 50 TC 118 Z9 120 U1 0 U2 27 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 2013 VL 19 IS 2 BP 393 EP 403 DI 10.1158/1078-0432.CCR-12-1626 PG 11 WC Oncology SC Oncology GA 073JN UT WOS:000313739400010 PM 23204132 ER PT J AU Nardi, V Sadow, PM Juric, D Zhao, D Cosper, AK Bergethon, K Scialabba, VL Batten, JM Borger, DR Iafrate, AJ Heist, RS Lawrence, DP Flaherty, KT Bendell, JC Deschler, D Li, Y Wirth, LJ Dias-Santagata, D AF Nardi, Valentina Sadow, Peter M. Juric, Dejan Zhao, Dave Cosper, Arjola K. Bergethon, Kristin Scialabba, Vanessa L. Batten, Julie M. Borger, Darrell R. Iafrate, Anthony John Heist, Rebecca S. Lawrence, Donald P. Flaherty, Keith T. Bendell, Johanna C. Deschler, Daniel Li, Yi Wirth, Lori J. Dias-Santagata, Dora TI Detection of Novel Actionable Genetic Changes in Salivary Duct Carcinoma Helps Direct Patient Treatment SO CLINICAL CANCER RESEARCH LA English DT Article ID IN-SITU HYBRIDIZATION; PHOSPHATIDYLINOSITOL 3-KINASE PATHWAY; BREAST-CANCER; PAROTID-GLAND; ANDROGEN RECEPTOR; ADVANCED MELANOMA; HER-2/NEU GENE; EXPRESSION; THERAPY; BRAF AB Purpose: Salivary duct carcinomas (SDC) are a rare and aggressive subtype of salivary gland cancers for which cytotoxic chemotherapy has limited efficacy. We investigated whether genotyping analysis could detect novel tumor-specific mutations that would help direct SDC patient treatment using targeted agents. Experimental Design: We genotyped 27 SDC archival specimens from patients followed at Massachusetts General Hospital and Massachusetts Eye and Ear Infirmary (Boston, MA) between 2000 and 2011. These included the tumors of 8 patients who were tested prospectively. Targeted mutational analysis of 13 clinically relevant cancer genes was conducted using SNaPshot multiplexed genotyping. FISH was conducted to detect HER2 gene amplification. Patient medical records and tumor histopathologic features were retrospectively reviewed. Results: Mutually exclusive genetic aberrations were detected in 15 of 27 (56%) tumors, including 2 (7%) mutations in BRAF, 5 (19%) mutations in PIK3CA, and 8 (30%) cases of HER2 gene amplification. To our knowledge, this is the first time that BRAF and PIK3CA mutations have been reported in this tumor type. Prospective clinical testing of 8 patients with SDC identified actionable genetic alterations in 6 tumors and influenced therapeutic decisions for all 6 patients. Conclusion: SNaPshot molecular profiling identified novel genetic changes in SDCs, expanded the therapeutic options for patients with this rare tumor, and is changing SDC management at our institution. These findings highlight the importance of using broad-based genetic profiling to expedite the identification of effective-targeted therapies for patients with rare malignancies. Clin Cancer Res; 19(2); 480-90. (C) 2012 AACR. C1 [Nardi, Valentina; Sadow, Peter M.; Cosper, Arjola K.; Bergethon, Kristin; Scialabba, Vanessa L.; Batten, Julie M.; Iafrate, Anthony John; Dias-Santagata, Dora] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Juric, Dejan; Heist, Rebecca S.; Lawrence, Donald P.; Flaherty, Keith T.; Wirth, Lori J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Sadow, Peter M.; Juric, Dejan; Borger, Darrell R.; Iafrate, Anthony John; Heist, Rebecca S.; Lawrence, Donald P.; Flaherty, Keith T.; Deschler, Daniel; Wirth, Lori J.; Dias-Santagata, Dora] Harvard Univ, Sch Med, Boston, MA USA. [Juric, Dejan; Zhao, Dave; Borger, Darrell R.; Heist, Rebecca S.; Lawrence, Donald P.; Flaherty, Keith T.; Li, Yi; Wirth, Lori J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Deschler, Daniel] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. [Bendell, Johanna C.] Sarah Cannon Res Inst, Nashville, TN USA. [Li, Yi] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. RP Dias-Santagata, D (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,GRJ 1028A, Boston, MA 02114 USA. EM ddiassantagata@partners.org NR 49 TC 37 Z9 37 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2013 VL 19 IS 2 BP 480 EP 490 DI 10.1158/1078-0432.CCR-12-1842 PG 11 WC Oncology SC Oncology GA 073JN UT WOS:000313739400018 PM 23186780 ER PT J AU Wheeler, HE Gamazon, ER Wing, C Njiaju, UO Njoku, C Baldwin, RM Owzar, K Jiang, C Watson, D Shterev, I Kubo, M Zembutsu, H Winer, EP Hudis, CA Shulman, LN Nakamura, Y Ratain, MJ Kroetz, DL Cox, NJ Dolan, ME AF Wheeler, Heather E. Gamazon, Eric R. Wing, Claudia Njiaju, Uchenna O. Njoku, Chidiamara Baldwin, Robert Michael Owzar, Kouros Jiang, Chen Watson, Dorothy Shterev, Ivo Kubo, Michiaki Zembutsu, Hitoshi Winer, Eric P. Hudis, Clifford A. Shulman, Lawrence N. Nakamura, Yusuke Ratain, Mark J. Kroetz, Deanna L. Cox, Nancy J. Dolan, Mary Eileen CA Canc Leukemia Grp B TI Integration of Cell Line and Clinical Trial Genome-Wide Analyses Supports a Polygenic Architecture of Paclitaxel-Induced Sensory Peripheral Neuropathy SO CLINICAL CANCER RESEARCH LA English DT Article ID REGULATORY FACTOR; CANCER PATIENTS; PHARMACOGENOMIC DISCOVERY; GENETIC-VARIATION; BREAST-CANCER; WHOLE-GENOME; HISTONE H1T; CHEMOTHERAPY; ASSOCIATION; POLYMORPHISMS AB Purpose: We sought to show the relevance of a lymphoblastoid cell line (LCL) model in the discovery of clinically relevant genetic variants affecting chemotherapeutic response by comparing LCL genome-wide association study (GWAS) results to clinical GWAS results. Experimental Design: A GWAS of paclitaxel-induced cytotoxicity was conducted in 247 LCLs from the HapMap Project and compared with a GWAS of sensory peripheral neuropathy in patients with breast cancer (n = 855) treated with paclitaxel in the Cancer and Leukemia Group B (CALGB) 40101 trial. Significant enrichment was assessed by permutation resampling analysis. Results: We observed an enrichment of LCL cytotoxicity-associated single-nucleotide polymorphisms (SNP) in the sensory peripheral neuropathy-associated SNPs from the clinical trial with concordant allelic directions of effect (empirical P = 0.007). Of the 24 SNPs that overlap between the clinical trial (P < 0.05) and the preclinical cytotoxicity study (P < 0.001), 19 of them are expression quantitative trait loci (eQTL), which is a significant enrichment of this functional class (empirical P = 0.0447). One of these eQTLs is located in RFX2, which encodes a member of the DNA-binding regulatory factor X family. Decreased expression of this gene by siRNA resulted in increased sensitivity of Neuroscreen-1(NS-1; rat pheochromocytoma) cells to paclitaxel as measured by reduced neurite outgrowth and increased cytotoxicity, functionally validating the involvement of RFX2 in nerve cell response to paclitaxel. Conclusions: The enrichment results and functional example imply that cellular models of chemotherapeutic toxicity may capture components of the underlying polygenic architecture of related traits in patients. Clin Cancer Res; 19(2); 491-9. (C) 2012 AACR. C1 [Wheeler, Heather E.; Wing, Claudia; Njiaju, Uchenna O.; Njoku, Chidiamara; Nakamura, Yusuke; Ratain, Mark J.; Dolan, Mary Eileen] Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. [Gamazon, Eric R.; Cox, Nancy J.] Univ Chicago, Dept Med, Med Genet Sect, Chicago, IL 60637 USA. [Baldwin, Robert Michael; Kroetz, Deanna L.] Univ Calif San Francisco, Sch Pharm & Med, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA. [Owzar, Kouros; Jiang, Chen; Watson, Dorothy; Shterev, Ivo] Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA. [Kubo, Michiaki; Zembutsu, Hitoshi; Nakamura, Yusuke] RIKEN, Ctr Genom Med, Yokohama, Kanagawa, Japan. [Winer, Eric P.; Shulman, Lawrence N.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hudis, Clifford A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Dolan, ME (reprint author), Univ Chicago, Dept Med, Hematol Oncol Sect, 900 E 57th St, Chicago, IL 60637 USA. EM edolan@medicine.bsd.uchicago.edu RI Baldwin, Mike/E-8601-2015; Kubo, Michiaki/N-7947-2015; OI Baldwin, Mike/0000-0002-6236-5000; Wheeler, Heather/0000-0003-1365-9667; Gamazon, Eric/0000-0003-4204-8734 FU Roche; NIH/NCI Cancer Biology Training grant [T32CA009594]; National Research Service Award [F32CA165823]; NIH/National Institute of General Medical Sciences (NIGMS) Pharmacogenomics of Anticancer Agents grant [U01GM61393]; NIH/NIGMS Pharmacogenetics of Membrane Transporters grant [U01GM61390]; University of Chicago SPORE Grant [NCI P50CA125183]; NIH/NCI Medical Oncology Training grant [T32CA009566]; Biobank Japan Project; Japanese Ministry of Education, Culture, Sports, Science and Technology; NCI [CA31946, CA33601] FX E.P. Winer has a Commercial Research Grant from Roche. No potential conflicts of interest were disclosed by the other authors. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute (NCI).; This study is supported by NIH/NCI Cancer Biology Training grant T32CA009594 and National Research Service Award F32CA165823 (to H.E. Wheeler), NIH/National Institute of General Medical Sciences (NIGMS) Pharmacogenomics of Anticancer Agents grant U01GM61393 (to M.J. Ratain, N.J. Cox, M.E. Dolan, and K. Owzar), NIH/NIGMS Pharmacogenetics of Membrane Transporters grant U01GM61390 (to D. L. Kroetz), University of Chicago SPORE Grant NCI P50CA125183 (to M.E. Dolan), NIH/NCI Medical Oncology Training grant T32CA009566 (to U.O. Njiaju), and the Biobank Japan Project funded by the Japanese Ministry of Education, Culture, Sports, Science and Technology. This work is part of the NIH Pharamcogenomics Research Network-RIKEN Center for Genomic Medicine Global Alliance.; The research for CALGB 60202 and 40101 was supported, in part, by grants from the NCI (CA31946) to the CALGB (Monica M. Bertagnolli) and to the CALGB Statistical Center (Daniel J. Sargent, CA33601). NR 45 TC 19 Z9 20 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 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2013 VL 19 IS 2 BP 491 EP 499 DI 10.1158/1078-0432.CCR-12-2618 PG 9 WC Oncology SC Oncology GA 073JN UT WOS:000313739400019 PM 23204130 ER PT J AU Nicolay, BN Gameiro, PA Tschop, K Korenjak, M Heilmann, AM Asara, JM Stephanopoulos, G Iliopoulos, O Dyson, NJ AF Nicolay, Brandon N. Gameiro, Paulo A. Tschoep, Katrin Korenjak, Michael Heilmann, Andreas M. Asara, John M. Stephanopoulos, Gregory Iliopoulos, Othon Dyson, Nicholas J. TI Loss of RBF1 changes glutamine catabolism SO GENES & DEVELOPMENT LA English DT Article DE RBF; pRB; Drosophila; metabolism ID DNA-DAMAGE; E2F; DROSOPHILA; CANCER; PRB; CELLS; TRANSCRIPTION; INSTABILITY; MECHANISMS; COMPLEXES AB Inactivation of the retinoblastoma tumor suppressor (pRB) alters the expression of a myriad of genes. To understand the altered cellular environment that these changes create, we took advantage of the Drosophila model system and used targeted liquid chromatography tandem mass spectrometry (LC-MS/MS) to profile the metabolic changes that occur when RBF1, the fly ortholog of pRB, is removed. We show that RBF1-depleted tissues and larvae are sensitive to fasting. Depletion of RBF1 causes major changes in nucleotide synthesis and glutathione metabolism. Under fasting conditions, these changes interconnect, and the increased replication demand of RBF1-depleted larvae is associated with the depletion of glutathione pools. In vivo 13 C isotopic tracer analysis shows that RBF1-depleted larvae increase the flux of glutamine toward glutathione synthesis, presumably to minimize oxidative stress. Concordantly, H2O2 preferentially promoted apoptosis in RBF1- depleted tissues, and the sensitivity of RBF1-depleted animals to fasting was specifically suppressed by either a glutamine supplement or the antioxidant N-acetyl-cysteine. Effects of pRB activation/inactivation on glutamine catabolism were also detected in human cell lines. These results show that the inactivation of RB proteins causes metabolic reprogramming and that these consequences of RBF/RB function are present in both flies and human cell lines. C1 [Nicolay, Brandon N.; Gameiro, Paulo A.; Tschoep, Katrin; Korenjak, Michael; Heilmann, Andreas M.; Iliopoulos, Othon; Dyson, Nicholas J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Mol Oncol,Canc Ctr, Charlestown, MA 02129 USA. [Gameiro, Paulo A.; Stephanopoulos, Gregory] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Gameiro, Paulo A.] Univ Coimbra, Dept Life Sci, P-3004517 Coimbra, Portugal. [Asara, John M.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Signal Transduct,Mass Spectrometry Core, Boston, MA 02215 USA. RP Nicolay, BN (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Mol Oncol,Canc Ctr, Charlestown, MA 02129 USA. EM bnicolay@partners.org; dyson@helix.mgh.harvard.edu FU NIH NRSA [F32CA165856]; Foundation for Science and Technology (FCT), Portugal; MGH Federal Share of Program Income [C06 CA059267]; NIH [R01 CA122591] FX We thank N. Bardeesy, L. Cantley, H. Coller, J. Lees, A. Manning, R. Mostoslavsky, A. Naar, and L. Zou for discussions and critical reading of the manuscript, and A. Ambrus and M. Frolov for sharing data prior to publication. We thank the TRiP at Harvard Medical School (NIH/NIGMS R01-GM084947) for providing transgenic RNAi fly stocks and/or plasmid vectors used in this study, and the Vienna Drosophila RNAi Center (VDRC) for fly stocks. B. N. N. is supported by the NIH NRSA fellowship F32CA165856. P. A. G. is supported by a fellowship from the Foundation for Science and Technology (FCT), Portugal. This work was supported by the MGH Federal Share of Program Income under C06 CA059267 and by NIH R01 CA122591 (to O.I.). N. J. D. is the James and Shirley Curvey MGH Research Scholar. NR 31 TC 34 Z9 34 U1 1 U2 6 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JAN 15 PY 2013 VL 27 IS 2 BP 182 EP 196 DI 10.1101/gad.206227.112 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 077RI UT WOS:000314044800008 PM 23322302 ER PT J AU Watanabe, H Francis, JM Woo, MS Etemad, B Lin, WC Fries, DF Peng, SY Snyder, EL Tata, PR Izzo, F Schinzel, AC Cho, JH Hammerman, PS Verhaak, RG Hahn, WC Rajagopal, J Jacks, T Meyerson, M AF Watanabe, Hideo Francis, Joshua M. Woo, Michele S. Etemad, Banafsheh Lin, Wenchu Fries, Daniel F. Peng, Shouyong Snyder, Eric L. Tata, Purushothama Rao Izzo, Francesca Schinzel, Anna C. Cho, Jeonghee Hammerman, Peter S. Verhaak, Roel G. Hahn, William C. Rajagopal, Jayaraj Jacks, Tyler Meyerson, Matthew TI Integrated cistromic and expression analysis of amplified NKX2-1 in lung adenocarcinoma identifies LMO3 as a functional transcriptional target SO GENES & DEVELOPMENT LA English DT Article DE lung cancer; lineage-specific oncogene; transcription factor; cistromic analysis; carcinogenesis ID ACUTE LYMPHOBLASTIC-LEUKEMIA; LINEAGE-SURVIVAL ONCOGENE; DNA-BINDING; FACTOR-I; EPITHELIAL-CELLS; GENE-EXPRESSION; VND/NK-2 HOMEODOMAIN; MYELOID-LEUKEMIA; BURKITT-LYMPHOMA; PROSTATE-CANCER AB The NKX2-1 transcription factor, a regulator of normal lung development, is the most significantly amplified gene in human lung adenocarcinoma. To study the transcriptional impact of NKX2-1 amplification, we generated an expression signature associated with NKX2-1 amplification in human lung adenocarcinoma and analyzed DNA-binding sites of NKX2-1 by genome-wide chromatin immunoprecipitation. Integration of these expression and cistromic analyses identified LMO3, itself encoding a transcription regulator, as a candidate direct transcriptional target of NKX2-1. Further cistromic and overexpression analyses indicated that NKX2-1 can cooperate with the forkhead box transcription factor FOXA1 to regulate LMO3 gene expression. RNAi analysis of NKX2-1-amplified cells compared with nonamplified cells demonstrated that LMO3 mediates cell survival downstream from NKX2-1. Our findings provide new insight into the transcriptional regulatory network of NKX2-1 and suggest that LMO3 is a transcriptional signal transducer in NKX2-1-amplified lung adenocarcinomas. C1 [Watanabe, Hideo; Francis, Joshua M.; Woo, Michele S.; Etemad, Banafsheh; Lin, Wenchu; Fries, Daniel F.; Peng, Shouyong; Izzo, Francesca; Schinzel, Anna C.; Cho, Jeonghee; Hammerman, Peter S.; Verhaak, Roel G.; Hahn, William C.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Watanabe, Hideo; Francis, Joshua M.; Woo, Michele S.; Lin, Wenchu; Cho, Jeonghee; Hammerman, Peter S.; Verhaak, Roel G.; Hahn, William C.; Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02215 USA. [Watanabe, Hideo; Francis, Joshua M.; Fries, Daniel F.; Peng, Shouyong; Hammerman, Peter S.; Verhaak, Roel G.; Hahn, William C.; Meyerson, Matthew] Broad Inst Harvard, Canc Program, Cambridge, MA 02142 USA. [Snyder, Eric L.; Jacks, Tyler] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02142 USA. [Tata, Purushothama Rao; Rajagopal, Jayaraj] Massachusetts Gen Hosp, Harvard Stem Cell Inst, Ctr Regenerat Med, Boston, MA 02114 USA. [Izzo, Francesca; Schinzel, Anna C.; Hahn, William C.] Dana Farber Canc Inst, RNAi Facil, Boston, MA 02215 USA. [Jacks, Tyler] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. [Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Meyerson, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM matthew_meyerson@dfci.harvard.edu FU NIH/NCI T32 Institutional Training Program [5T32CA009361-28]; National Cancer Institute [5R01CA109038, 5P20CA90578] FX We thank C.Z. Zhang, Q. Ma, B. Weir, A. Kostic, T. Westerling, H. He, J.K. Lee, N. Hendrick, W. Song, A. Bass, S. Kobayashi, and D. Tenen for technical advice and discussions. H. W. was supported by the NIH/NCI T32 Institutional Training Program fellowship (5T32CA009361-28). This work was supported by National Cancer Institute grants 5R01CA109038 and 5P20CA90578 (to M. M.). M. M. is a paid consultant for and equity holder in Foundation Medicine, a genomics-based oncology diagnostics company. M. M. and W. C. H. are paid consultants for Novartis Pharmaceuticals. Both companies have no connection or rights to the work described in this study. NR 71 TC 21 Z9 21 U1 0 U2 7 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 EI 1549-5477 J9 GENE DEV JI Genes Dev. PD JAN 15 PY 2013 VL 27 IS 2 BP 197 EP 210 DI 10.1101/gad.203208.112 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 077RI UT WOS:000314044800009 PM 23322301 ER PT J AU Iqbal, FM Al Jaroudi, W Sanam, K Sweeney, A Heo, J Iskandrian, AE Hage, FG AF Iqbal, Fahad M. Al Jaroudi, Wael Sanam, Kumar Sweeney, Aaron Heo, Jaekyeong Iskandrian, Ami E. Hage, Fadi G. TI Reclassification of Cardiovascular Risk in Patients With Normal Myocardial Perfusion Imaging Using Heart Rate Response to Vasodilator Stress SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID DIABETES-MELLITUS; PROGNOSTIC VALUE; DISEASE; SCORE; REGADENOSON; ADENOSINE; MORTALITY; PREDICTION; SPECT AB Previous studies have shown that patients with normal vasodilator myocardial perfusion imaging (MPI) findings remain at a greater risk of future cardiac events than patients with normal exercise MPI findings. The aim was to assess improvement in risk classification provided by the heart rate response (HRR) in patients with normal vasodilator MPI findings when added to traditional risk stratification. We retrospectively studied 2,000 patients with normal regadenoson or adenosine MPI findings. Risk stratification was performed using Adult Treatment Panel III framework. Patients were stratified by HRR (percentage of increase from baseline) into tertiles specific to each vasodilator. All-cause mortality and cardiac death/nonfatal myocardial infarction (MI) <= 2 years from the index MPI were recorded. During follow-up, 11.8% patients died and 2.7% patients experienced cardiac death/nonfatal MI in the adenosine and regadenoson groups, respectively. The patients who died had a greater Framingham risk score (12 +/- 4 vs 11 +/- 4, p = 0.009) and lower HRR (22 16 vs 32 21, p <0.0001). In an adjusted Cox model, the lowest tertile HRR was associated with an increased risk of mortality (hazard ratio 2.1) and cardiac death/nonfatal MI (hazard ratio 2.9; p <0.01). Patients in the highest HRR tertile, irrespective of the Adult Treatment Panel III category, were at low risk. When added to the Adult Treatment Panel III categories, the HRR resulted in net reclassification improvement in mortality of 18% and cardiac death/nonfatal MI of 22%. In conclusion, a blunted HRR to vasodilator stress was independently associated with an increased risk of cardiac events and overall mortality in patients with normal vasodilator MPI findings. The HRR correctly reclassified a substantial proportion of these patients in addition to the traditional risk classification models and identified patients with normal vasodilator MPI findings, who had a truly low risk of events. (C) 2013 Published by Elsevier Inc. (Am J Cardiol 2013;111:190-195) C1 [Iqbal, Fahad M.; Sweeney, Aaron] Tulane Univ, Inst Heart & Vasc, New Orleans, LA 70118 USA. [Al Jaroudi, Wael] Cleveland Clin, Div Cardiovasc Med, Sect Cardiac Imaging, Inst Heart & Vasc, Cleveland, OH 44106 USA. [Sanam, Kumar; Heo, Jaekyeong; Iskandrian, Ami E.; Hage, Fadi G.] Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Div Cardiol, Birmingham, AL USA. RP Iqbal, FM (reprint author), Tulane Univ, Inst Heart & Vasc, New Orleans, LA 70118 USA. EM fiqbal1@tulane.edu OI Hage, Fadi/0000-0002-1397-4942 FU Astellas Pharma FX Dr. Iskandrian is a consultant for Gilead Sciences and Astellas Pharma; and Dr. Hage is the recipient of an investigator initiated grant from Astellas Pharma. The remaining authors have no conflicts of interest to disclose. NR 26 TC 13 Z9 13 U1 0 U2 4 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 15 PY 2013 VL 111 IS 2 BP 190 EP 195 DI 10.1016/j.amjcard.2012.09.013 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 071PQ UT WOS:000313607100007 PM 23111139 ER PT J AU Sinner, MF Wang, N Fox, CS Fontes, JD Rienstra, M Magnani, JW Vasan, RS Calderwood, AH Pencina, M Sullivan, LM Ellinor, PT Benjamin, EJ AF Sinner, Moritz F. Wang, Na Fox, Caroline S. Fontes, Joao D. Rienstra, Michiel Magnani, Jared W. Vasan, Ramachandran S. Calderwood, Audrey H. Pencina, Michael Sullivan, Lisa M. Ellinor, Patrick T. Benjamin, Emelia J. TI Relation of Circulating Liver Transaminase Concentrations to Risk of New-Onset Atrial Fibrillation SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ASPARTATE-AMINOTRANSFERASE; CARDIOVASCULAR-DISEASE; NATRIURETIC PEPTIDE; SURVIVAL ANALYSIS; HEART-FAILURE; POPULATION; DISCRIMINATION; ASSOCIATION; COMMUNITY; MARKER AB Heart failure, a strong risk factor for atrial fibrillation (AF), is often accompanied by elevated liver transaminases. The aim of this study was to test the hypothesis that elevated transaminases are associated with the risk for incident AF in the community. A total of 3,744 participants (mean age 65 +/- 10 years, 56.8% women) from the Framingham Heart Study Original and Offspring cohorts, free of clinical heart failure, were studied. Cox proportional-hazards models adjusted for standard AF risk factors (age, gender, body mass index, systolic blood pressure, electrocardiographic PR interval, antihypertensive treatment, smoking, diabetes, valvular heart disease, and alcohol consumption) were examined to investigate associations between baseline serum transaminase levels (alanine transaminase and aspartate transaminase) and the incidence of AF over up to 10 years (29,099 person-years) of follow-up. During follow-up, 383 subjects developed AF. The 2 transaminases were significantly associated with greater risk for incident AF (hazard ratio expressed per SD of natural logarithmically transformed biomarker: alanine transaminase hazard ratio 1.19, 95% confidence interval 1.07 to 1.32, p = 0.002; aspartate transaminase hazard ratio 1.12, 95% confidence interval 1.01 to 1.24, p = 0.03). The associations between transaminases and AF remained consistent after the exclusion of participants with moderate to severe alcohol consumption. However, when added to known risk factors for AF, alanine transaminase and aspartate transaminase only subtly improved the prediction of AF. In conclusion, elevated transaminase concentrations are associated with increased AF incidence. The mechanisms by which higher mean transaminase concentrations are associated with incident AF remain to be determined. (C) 2013 Elsevier Inc. All rights reserved. (Am J Cardiol 2013;111:219-224) C1 [Sinner, Moritz F.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Sinner, Moritz F.; Fox, Caroline S.; Fontes, Joao D.; Magnani, Jared W.; Vasan, Ramachandran S.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA. [Sinner, Moritz F.; Fox, Caroline S.; Fontes, Joao D.; Magnani, Jared W.; Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Sinner, Moritz F.] Univ Munich, Univ Hosp Munich, Dept Med 1, Munich, Germany. [Wang, Na; Sullivan, Lisa M.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Metab & Diabet, Dept Med, Boston, MA 02115 USA. [Rienstra, Michiel] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands. [Magnani, Jared W.] Boston Univ, Sch Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Evans Mem Dept Med, Sect Prevent Med, Boston, MA 02118 USA. [Vasan, Ramachandran S.; Benjamin, Emelia J.] Boston Univ, Sch Med, Evans Mem Dept Med, Cardiol Sect, Boston, MA 02118 USA. [Calderwood, Audrey H.] Boston Univ, Sch Med, Dept Med, Sect Gastroenterol, Boston, MA 02118 USA. [Pencina, Michael] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Benjamin, EJ (reprint author), NHLBI, Framingham, MA USA. EM emelia@bu.edu OI Calderwood, Audrey/0000-0001-7486-8310; Ramachandran, Vasan/0000-0001-7357-5970; Sullivan, Lisa/0000-0003-0726-7149; Benjamin, Emelia/0000-0003-4076-2336; Rienstra, Michiel/0000-0002-2581-070X FU National Institutes of Health, Bethesda, Maryland [N01-HC25195, 6R01-NS17950, 1RO1 HL092577, 1RC1HL101056, 1R01HL102214, 1R01AG028321, 5R2 DA027021, 1RO1HL104156, 1K24HL105780, 1K08DK090150-01]; German Heart Foundation, Frankfurt-am-Main, Germany; American Heart Association, Dallas, Texas [09FTF2190028] FX This work was supported by Grants N01-HC25195 and 6R01-NS17950, Grant 1RO1 HL092577 to Dr. Benjamin and Dr. Ellinor, Grants 1RC1HL101056, 1R01HL102214, and 1R01AG028321 to Dr. Benjamin, Grants 5R2 DA027021, 1RO1HL104156, and 1K24HL105780 to Dr. Ellinor, and Grant 1K08DK090150-01 to Dr. Calderwood from the National Institutes of Health, Bethesda, Maryland; by the German Heart Foundation, Frankfurt-am-Main, Germany (to Dr. Sinner); by Grant 09FTF2190028 to Dr. Magnani from the American Heart Association, Dallas, Texas; and partially by the Evans Center for Interdisciplinary Biomedical Research (http://www.bumc.bu.edu/evanscenteribr/) ARC on Atrial Fibrillation at Boston University, Boston, Massachusetts (to Drs. Benjamin and Magnani). NR 29 TC 22 Z9 22 U1 0 U2 7 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 15 PY 2013 VL 111 IS 2 BP 219 EP 224 DI 10.1016/j.amjcard.2012.09.021 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 071PQ UT WOS:000313607100012 PM 23127690 ER PT J AU Kumar, V Venkataraman, R Aljaroudi, W Osorio, J Heo, J Iskandrian, AE Hage, FG AF Kumar, Vineet Venkataraman, Rajesh Aljaroudi, Wael Osorio, Jose Heo, Jaekyeong Iskandrian, Arni E. Hage, Fadi G. TI Implications of Left Bundle Branch Block in Patient Treatment SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIAC-RESYNCHRONIZATION THERAPY; ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY-DISEASE; CHRONIC HEART-FAILURE; ELECTROCARDIOGRAPHIC DIAGNOSIS; STRESS ECHOCARDIOGRAPHY; COMPUTED-TOMOGRAPHY; RANDOMIZED-TRIALS; NATURAL-HISTORY; QRS MORPHOLOGY AB Left bundle branch block (LBBB) causes an abnormal pattern of cardiac activation and affects regional myocardial function. Although recognition of LBBB on the surface electrocardiogram is straightforward, dissecting its effect on patient treatment and outcome can be more challenging. The altered pattern of cardiac activation in LBBB causes electrical and mechanical ventricular dyssynchrony, influences ischemia detection on the surface electrocardiogram, and affects stress testing and imaging modalities dependent on wall motion and thickening. Restoration of synchrony by biventricular pacing can improve symptoms and longevity in carefully selected patients. The diagnostic, prognostic, and therapeutic implications of LBBB across this spectrum are discussed in this review. (C) 2013 Elsevier Inc. All rights reserved. (Am J Cardiol 2013;111:291-300) C1 [Kumar, Vineet; Venkataraman, Rajesh; Osorio, Jose; Heo, Jaekyeong; Iskandrian, Arni E.; Hage, Fadi G.] Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL 35294 USA. [Aljaroudi, Wael] Cleveland Clin, Cleveland, OH 44106 USA. [Osorio, Jose; Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Cardiol Sect, Birmingham, AL USA. RP Hage, FG (reprint author), Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL 35294 USA. EM fadihage@uab.edu OI Hage, Fadi/0000-0002-1397-4942 NR 74 TC 11 Z9 13 U1 1 U2 9 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 15 PY 2013 VL 111 IS 2 BP 291 EP 300 DI 10.1016/j.amjcard.2012.09.029 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 071PQ UT WOS:000313607100023 PM 23111137 ER PT J AU Nettleton, JA Hivert, MF Lemaitre, RN McKeown, NM Mozaffarian, D Tanaka, T Wojczynski, MK Hruby, A Djousse, L Ngwa, JS Follis, JL Dimitriou, M Ganna, A Houston, DK Kanoni, S Mikkila, V Manichaikul, A Ntalla, I Renstrom, F Sonestedt, E van Rooij, FJA Bandinelli, S de Koning, L Ericson, U Hassanali, N Kiefte-de Jong, JC Lohman, KK Raitakari, O Papoutsakis, C Sjogren, P Stirrups, K Ax, E Deloukas, P Groves, CJ Jacques, PF Johansson, I Liu, YM McCarthy, MI North, K Viikari, J Zillikens, MC Dupuis, J Hofman, A Kolovou, G Mukamal, K Prokopenko, I Rolandsson, O Seppala, I Cupples, LA Hu, FB Kahonen, M Uitterlinden, AG Borecki, IB Ferrucci, L Jacobs, DR Kritchevsky, SB Orho-Melander, M Pankow, JS Lehtimaki, T Witteman, JCM Ingelsson, E Siscovick, DS Dedoussis, G Meigs, JB Franks, PW AF Nettleton, Jennifer A. Hivert, Marie-France Lemaitre, Rozenn N. McKeown, Nicola M. Mozaffarian, Dariush Tanaka, Toshiko Wojczynski, Mary K. Hruby, Adela Djousse, Luc Ngwa, Julius S. Follis, Jack L. Dimitriou, Maria Ganna, Andrea Houston, Denise K. Kanoni, Stavroula Mikkila, Vera Manichaikul, Ani Ntalla, Ioanna Renstrom, Frida Sonestedt, Emily van Rooij, Frank J. A. Bandinelli, Stefania de Koning, Lawrence Ericson, Ulrika Hassanali, Neelam Kiefte-de Jong, Jessica C. Lohman, Kurt K. Raitakari, Olli Papoutsakis, Constantina Sjogren, Per Stirrups, Kathleen Ax, Erika Deloukas, Panos Groves, Christopher J. Jacques, Paul F. Johansson, Ingegerd Liu, Yongmei McCarthy, Mark I. North, Kari Viikari, Jorma Zillikens, M. Carola Dupuis, Josee Hofman, Albert Kolovou, Genovefa Mukamal, Kenneth Prokopenko, Inga Rolandsson, Olov Seppala, Ilkka Cupples, L. Adrienne Hu, Frank B. Kahonen, Mika Uitterlinden, Andre G. Borecki, Ingrid B. Ferrucci, Luigi Jacobs, David R., Jr. Kritchevsky, Stephen B. Orho-Melander, Marju Pankow, James S. Lehtimaki, Terho Witteman, Jacqueline C. M. Ingelsson, Erik Siscovick, David S. Dedoussis, George Meigs, James B. Franks, Paul W. TI Meta-Analysis Investigating Associations Between Healthy Diet and Fasting Glucose and Insulin Levels and Modification by Loci Associated With Glucose Homeostasis in Data From 15 Cohorts SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Review DE diabetes; dietary pattern; gene-environment interaction; glucose; insulin ID CLINICAL RISK-FACTORS; ATHEROSCLEROSIS MESA; DAIRY CONSUMPTION; GENETIC-LOCI; DNA VARIANTS; FOOD SYNERGY; DESIGN; PATTERNS; WOMEN; OBJECTIVES AB Whether loci that influence fasting glucose (FG) and fasting insulin (FI) levels, as identified by genome-wide association studies, modify associations of diet with FG or FI is unknown. We utilized data from 15 US and European cohort studies comprising 51,289 persons without diabetes to test whether genotype and diet interact to influence FG or FI concentration. We constructed a diet score using study-specific quartile rankings for intakes of whole grains, fish, fruits, vegetables, and nuts/seeds (favorable) and red/processed meats, sweets, sugared beverages, and fried potatoes (unfavorable). We used linear regression within studies, followed by inverse-variance-weighted meta-analysis, to quantify 1) associations of diet score with FG and FI levels and 2) interactions of diet score with 16 FG-associated loci and 2 FI-associated loci. Diet score (per unit increase) was inversely associated with FG ( 0.004 mmol/L, 95 confidence interval: 0.005, 0.003) and FI ( 0.008 ln-pmol/L, 95 confidence interval: 0.009, 0.007) levels after adjustment for demographic factors, lifestyle, and body mass index. Genotype variation at the studied loci did not modify these associations. Healthier diets were associated with lower FG and FI concentrations regardless of genotype at previously replicated FG- and FI-associated loci. Studies focusing on genomic regions that do not yield highly statistically significant associations from main-effect genome-wide association studies may be more fruitful in identifying diet-gene interactions. C1 [Nettleton, Jennifer A.] Univ Texas Hlth Sci Ctr Houston, Div Epidemiol Human Genet & Environm Sci, Sch Publ Hlth, Houston, TX 77030 USA. [Hivert, Marie-France] Univ Sherbrooke, Fac Med & Hlth Sci, Dept Med, Sherbrooke, PQ J1K 2R1, Canada. [Lemaitre, Rozenn N.; Siscovick, David S.] Univ Washington, Sch Med, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [McKeown, Nicola M.; Hruby, Adela; Jacques, Paul F.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Mozaffarian, Dariush] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Mozaffarian, Dariush; Djousse, Luc] Harvard Univ, Sch Med, Boston, MA USA. [Mozaffarian, Dariush] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Wojczynski, Mary K.; Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA. [Djousse, Luc] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Ngwa, Julius S.; Dupuis, Josee; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Follis, Jack L.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Div Biostat, Houston, TX USA. [Follis, Jack L.] Univ St Thomas, Dept Math, Sch Arts & Sci, Houston, TX 77006 USA. [Dimitriou, Maria; Ntalla, Ioanna; Papoutsakis, Constantina; Dedoussis, George] Harokopio Univ, Dept Nutr & Dietet, Athens, Greece. [Ganna, Andrea; Ingelsson, Erik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Houston, Denise K.; Kritchevsky, Stephen B.] Wake Forest Sch Med, Sticht Ctr Aging, Dept Internal Med, Sect Gerontol & Geriatr Med, Winston Salem, NC USA. [Kanoni, Stavroula; Stirrups, Kathleen; Deloukas, Panos] Welcome Trust Sanger Inst, Hinxton, England. [Mikkila, Vera] Univ Helsinki, Div Nutr, Dept Food & Environm Sci, Fac Agr & Forestry, Helsinki, Finland. [Manichaikul, Ani] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Manichaikul, Ani] Univ Virginia, Div Biostat & Epidemiol, Charlottesville, VA USA. [Renstrom, Frida; de Koning, Lawrence; Hu, Frank B.; Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Renstrom, Frida; Sonestedt, Emily; Ericson, Ulrika; Orho-Melander, Marju; Franks, Paul W.] Lund Univ, Fac Med, Dept Clin Sci, Malmo, Sweden. [Renstrom, Frida; Johansson, Ingegerd; Rolandsson, Olov; Franks, Paul W.] Umea Univ Hosp, Dept Publ Hlth & Clin Med, S-90185 Umea, Sweden. [van Rooij, Frank J. A.; Zillikens, M. Carola; Hofman, Albert; Uitterlinden, Andre G.; Witteman, Jacqueline C. M.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [van Rooij, Frank J. A.; Kiefte-de Jong, Jessica C.; Zillikens, M. Carola; Hofman, Albert; Uitterlinden, Andre G.] Sponsored Netherlands Consortium Healthy Aging, Netherlands Genom Initiat, Leiden, Netherlands. [Bandinelli, Stefania] Azienda Sanitaria Firenze, Geriatr Unit, Florence, Italy. [Hassanali, Neelam; Groves, Christopher J.; McCarthy, Mark I.; Prokopenko, Inga] Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Kiefte-de Jong, Jessica C.] Erasmus MC, Dept Generat, Study Grp R, Rotterdam, Netherlands. [Lohman, Kurt K.] Wake Forest Sch Med, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC USA. [Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol, FIN-20520 Turku, Finland. [Sjogren, Per; Ax, Erika] Uppsala Univ, Div Clin Nutr & Metab, Dept Publ Hlth & Caring Sci, Uppsala, Sweden. [Johansson, Ingegerd] Umea Univ, Fac Med, Dept Odontol, Umea, Sweden. [Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC USA. [McCarthy, Mark I.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [McCarthy, Mark I.] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England. [North, Kari] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. [North, Kari] Univ N Carolina, Sch Med, Carolina Ctr Genome Sci, Chapel Hill, NC USA. [Viikari, Jorma] Univ Turku, Dept Med, Turku, Finland. [Viikari, Jorma] Turku Univ Hosp, FIN-20520 Turku, Finland. [Zillikens, M. Carola; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Kolovou, Genovefa] Onassis Cardiac Surg Ctr, Dept Cardiol, Athens, Greece. [Mukamal, Kenneth] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Seppala, Ilkka; Lehtimaki, Terho] Univ Tampere, Dept Clin Chem, Unit Family Med, FIN-33101 Tampere, Finland. [Kahonen, Mika] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Kahonen, Mika] Univ Tampere, Dept Clin Physiol, FIN-33101 Tampere, Finland. [Seppala, Ilkka; Kahonen, Mika; Lehtimaki, Terho] Tampere Univ Hosp, Tampere, Finland. [Jacobs, David R., Jr.; Pankow, James S.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Clin Epidemiol Unit, Boston, MA 02114 USA. [Meigs, James B.] Massachusetts Gen Hosp, Diabet Res Unit, Boston, MA 02114 USA. RP Nettleton, JA (reprint author), Univ Texas Hlth Sci Ctr Houston, Div Epidemiol Human Genet & Environm Sci, Sch Publ Hlth, 1200 Herman Pressler Dr,Suite E-641, Houston, TX 77030 USA. EM jennifer.a.nettleton@uth.tmc.edu RI Deloukas, Panos/B-2922-2013; Sjogren, Per/N-5923-2014; Prokopenko, Inga/H-3241-2014; Sonestedt, Emily/I-3814-2016; Djousse, Luc/F-5033-2017; OI Pankow, James/0000-0001-7076-483X; Ganna, Andrea/0000-0002-8147-240X; Deloukas, Panos/0000-0001-9251-070X; Franks, Paul/0000-0002-0520-7604; Kiefte-de Jong, Jessica/0000-0002-8136-0918; Prokopenko, Inga/0000-0003-1624-7457; Sonestedt, Emily/0000-0002-0747-4562; Djousse, Luc/0000-0002-9902-3047; Cupples, L. Adrienne/0000-0003-0273-7965; Dupuis, Josee/0000-0003-2871-3603; Kritchevsky, Stephen/0000-0003-3336-6781 FU NHLBI NIH HHS [R01 HL087700, R01 HL105756]; NIDDK NIH HHS [K24 DK080140, R01 DK078616]; Wellcome Trust [090532] NR 48 TC 26 Z9 26 U1 2 U2 23 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 15 PY 2013 VL 177 IS 2 BP 103 EP 115 DI 10.1093/aje/kws297 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 070RP UT WOS:000313528700001 PM 23255780 ER PT J AU Purnell, JQ Hokanson, JE Cleary, PA Nathan, DM Lachin, JM Zinman, B Brunzell, JD AF Purnell, Jonathan Q. Hokanson, John E. Cleary, Patricia A. Nathan, David M. Lachin, John M. Zinman, Bernard Brunzell, John D. CA DCCT EDIC Res Grp TI The Effect of Excess Weight Gain With Intensive Diabetes Mellitus Treatment on Cardiovascular Disease Risk Factors and Atherosclerosis in Type 1 Diabetes Mellitus Results From the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC) Study SO CIRCULATION LA English DT Article DE calcium; carotid intima-media thickness; coronary vessels; diabetes mellitus, type 1; imaging, diagnostic; obesity ID CORONARY-ARTERY CALCIFICATION; CHOLESTERYL ESTER TRANSFER; INTIMA-MEDIA THICKNESS; METABOLIC SYNDROME; FAMILY-HISTORY; HEPATIC LIPASE; LIPOPROTEIN; PROGRESSION; MORTALITY; THERAPY AB Background-Intensive diabetes mellitus therapy of type 1 diabetes mellitus reduces diabetes mellitus complications but can be associated with excess weight gain, central obesity, and dyslipidemia. The purpose of this study was to determine whether excessive weight gain with diabetes mellitus therapy of type 1 diabetes mellitus is prospectively associated with atherosclerotic disease. Methods and Results-Subjects with type 1 diabetes mellitus (97% white, 45% female, mean age 35 years) randomly assigned to intensive or conventional diabetes mellitus treatment during the Diabetes Control and Complications Trial (DCCT) underwent intima-media thickness (n = 1015) and coronary artery calcium score (n = 925) measurements during follow-up in the Epidemiology of Diabetes Interventions and Complications (EDIC) Study. Intensive treatment subjects were classified by quartile of body mass index change during the DCCT. Excess gainers (4th quartile, including conventional treatment subjects meeting this threshold) maintained greater body mass index and waist circumference, needed more insulin, had greater intima-media thickness (+ 5%, P < 0.001 EDIC year 1, P = 0.003 EDIC year 6), and trended toward greater coronary artery calcium scores (odds ratio, 1.55; confidence interval, 0.97 to 2.49; P = 0.07) than minimal gainers. DCCT subjects meeting metabolic syndrome criteria for waist circumference and blood pressure had greater intima-media thickness in both EDIC years (P = 0.02 to < 0.001); those meeting high-density lipoprotein criteria had greater coronary artery calcium scores (odds ratio, 1.6; confidence interval, 1.1 to 2.4; P = 0.01) during follow-up. Increasing frequency of a family history of diabetes mellitus, hypertension, and hyperlipidemia was associated with greater intima-media thickness with intensive but not conventional treatment. Conclusions-Excess weight gain in DCCT is associated with sustained increases in central obesity, insulin resistance, dyslipidemia and blood pressure, as well as more extensive atherosclerosis during EDIC. Clinical Trial Registration-URL for DCCT: http://clinicaltrials.gov; Unique identifier: NCT00360815. URL for EDIC: http://clinicaltrials.gov; Unique identifier: NCT00360893. (Circulation. 2013;127:180-187.) C1 [Purnell, Jonathan Q.] Oregon Hlth & Sci Univ, Div Endocrinol Diabet & Clin Nutr, Dept Med, Portland, OR 97239 USA. [Hokanson, John E.; Lachin, John M.] Univ Colorado, Dept Med, Denver, CO USA. [Cleary, Patricia A.] George Washington Univ, Ctr Biostat, Rockville, MD USA. Harvard Univ, Massachusetts Gen Hosp, Dept Med, Diabet Ctr,Med Sch, Boston, MA USA. [Zinman, Bernard] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Brunzell, John D.] Univ Washington, Dept Med, Seattle, WA USA. RP Purnell, JQ (reprint author), Oregon Hlth & Sci Univ, Div Endocrinol Diabet & Clin Nutr, Dept Med, Mailstop L607,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM purnellj@ohsu.edu RI Zinman, Bernard/E-7266-2013 FU National Institutes of Health [DK02456]; UW Diabetes Endocrinology Research Center National Institutes of Health [DK 17047]; Division of Diabetes, Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases, National Eye Institute, National Institute of Neurological Disorders and Stroke; General Clinical Research Centers Program; Clinical and Translational Science Awards Program, National Center for Research Resources; Genentech through National Institute of Diabetes and Digestive and Kidney Diseases FX This study was supported by National Institutes of Health grant No. DK02456 (to Dr Brunzell) and UW Diabetes Endocrinology Research Center National Institutes of Health grant No. DK 17047. The DCCT/EDIC project is supported by contracts with the Division of Diabetes, Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases, National Eye Institute, National Institute of Neurological Disorders and Stroke, the General Clinical Research Centers Program, and the Clinical and Translational Science Awards Program, National Center for Research Resources, and by Genentech through a Cooperative Research and Development Agreement with the National Institute of Diabetes and Digestive and Kidney Diseases. Contributors of free or discounted supplies or equipment include Lifescan, Roche, Aventis, Eli Lilly, OmniPod, Can-Am, B-D, Animas, Medtronic, Medtronic Minimed, Bayer (donation one time in 2008), and Omron. NR 34 TC 68 Z9 72 U1 0 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JAN 15 PY 2013 VL 127 IS 2 BP 180 EP + DI 10.1161/CIRCULATIONAHA.111.077487 PG 14 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 071ZL UT WOS:000313637200014 PM 23212717 ER PT J AU Piccini, JP Stevens, SR Chang, YC Singer, DE Lokhnygina, Y Go, AS Patel, MR Mahaffey, KW Halperin, JL Breithardt, G Hankey, GJ Hacke, W Becker, RC Nessel, CC Fox, KAA Califf, RM AF Piccini, Jonathan P. Stevens, Susanna R. Chang, YuChiao Singer, Daniel E. Lokhnygina, Yuliya Go, Alan S. Patel, Manesh R. Mahaffey, Kenneth W. Halperin, Jonathan L. Breithardt, Guenter Hankey, Graeme J. Hacke, Werner Becker, Richard C. Nessel, Christopher C. Fox, Keith A. A. Califf, Robert M. CA ROCKET AF Steering Comm TI Renal Dysfunction as a Predictor of Stroke and Systemic Embolism in Patients With Nonvalvular Atrial Fibrillation Validation of the R(2)CHADS(2) Index in the ROCKET AF (Rivaroxaban Once-daily, oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) and ATRIA (AnTicoagulation and Risk factors In Atrial fibrillation) Study Cohorts SO CIRCULATION LA English DT Article DE atrial fibrillation; chronic kidney diseases; risk stratification; stroke ID TRANSIENT ISCHEMIC ATTACK; STRATIFICATION SCHEMES; THROMBOEMBOLISM; ADULTS; CURVE AB Background-We sought to define the factors associated with the occurrence of stroke and systemic embolism in a large, international atrial fibrillation (AF) trial. Methods and Results-In ROCKET AF (Rivaroxaban Once-daily, oral, direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation), 14 264 patients with nonvalvular AF and creatinine clearance >= 30 mL/min were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards modeling was used to identify factors at randomization independently associated with the occurrence of stroke or non-central nervous system embolism based on intention-to-treat analysis. A risk score was developed in ROCKET AF and validated in ATRIA (AnTicoagulation and Risk factors In Atrial fibrillation), an independent AF patient cohort. Over a median follow-up of 1.94 years, 575 patients (4.0%) experienced primary end-point events. Reduced creatinine clearance was a strong, independent predictor of stroke and systemic embolism, second only to prior stroke or transient ischemic attack. Additional factors associated with stroke and systemic embolism included elevated diastolic blood pressure and heart rate, as well as vascular disease of the heart and limbs (C-index 0.635). A model that included creatinine clearance (R(2)CHADS(2)) improved net reclassification index by 6.2% compared with CHA(2)DS(2) VASc (C statistic=0.578) and by 8.2% compared with CHADS(2) (C statistic=0.575). The inclusion of creatinine clearance < 60 mL/min and prior stroke or transient ischemic attack in a model with no other covariates led to a C statistic of 0.590. Validation of R(2)CHADS(2) in an external, separate population improved net reclassification index by 17.4% (95% confidence interval, 12.1%-22.5%) relative to CHADS(2). Conclusions-In patients with nonvalvular AF at moderate to high risk of stroke, impaired renal function is a potent predictor of stroke and systemic embolism. Stroke risk stratification in patients with AF should include renal function. Clinical Trial Registration-URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00403767. (Circulation. 2013;127:224-232.) C1 [Piccini, Jonathan P.] Duke Univ, Med Ctr, Duke Clin Res Inst, Div Cardiol, Durham, NC 27710 USA. [Califf, Robert M.] Duke Univ, Med Ctr, Duke Translat Med Inst, Durham, NC 27710 USA. [Chang, YuChiao; Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chang, YuChiao; Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. [Go, Alan S.] Kaiser Permanente, Div Res, Oakland, CA USA. [Halperin, Jonathan L.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Breithardt, Guenter] Hosp Univ Munster, Munster, Germany. [Hankey, Graeme J.] Royal Perth Hosp, Perth, WA, Australia. [Hacke, Werner] Heidelberg Univ, Heidelberg, Germany. [Nessel, Christopher C.] Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA. [Fox, Keith A. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Fox, Keith A. A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland. RP Piccini, JP (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, Div Cardiol, POB 17969, Durham, NC 27710 USA. EM jonathan.piccini@duke.edu RI Hankey, Graeme /H-4968-2014 OI Hankey, Graeme /0000-0002-6044-7328 FU Johnson & Johnson Pharmaceutical Research & Development, Raritan, NJ; Bayer HealthCare AG, Leverkusen, Germany; Johnson Johnson; Boston Scientific; Massachusetts General Hospital (Boston, MA); Bayer HealthCare; Boehringer Ingelheim; Bristol-Myers Squibb; Daiichi Sankyo; Pfizer; Sanofi; Ortho McNeil Janssen; AstraZeneca; Bayer; Eli Lilly; GlaxoSmithKline; Merck; Momenta Pharmaceuticals; Novartis; Portola; Pozen; Regado Biotechnologies; Sanofi-Aventis; Medicines Company; Ortho/McNeill; Polymedix FX The ROCKET AF trial was sponsored by Johnson & Johnson Pharmaceutical Research & Development, Raritan, NJ, and Bayer HealthCare AG, Leverkusen, Germany.; Dr Piccini reports receiving research grants from Johnson & Johnson and Boston Scientific and serves as a consultant to Medtronic, Forest Laboratories, Sanofi Aventis, and Johnson & Johnson. Dr Singer is supported in part by the Eliot B. and Edith C. Shoolman fund of the Massachusetts General Hospital (Boston, MA); he receives consulting fees from Bayer HealthCare, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Johnson & Johnson, Pfizer, and Sanofi. Dr Patel receives honoraria from Johnson & Johnson and Bayer; consulting fees from Ortho McNeil Janssen, Bayer HealthCare; and serves on an advisory board for Genzyme. Dr Mahaffey receives grant support from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Johnson & Johnson, Merck, Momenta Pharmaceuticals, Novartis, Portola, Pozen, Regado Biotechnologies, Sanofi-Aventis, Schering-Plow (now Merck), and The Medicines Company; he also receives consulting fees from AstraZeneca and Johnson & Johnson, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Ortho/McNeill, Pfizer, Polymedix, Sanofi-Aventis, and Schering-Plow (now Merck). Dr Halperin receives honoraria from Johnson & Johnson and Bayer and advisory fees from Boehringer Ingelheim, Bristol Myers-Squibb, and Pfizer. Dr Breithardt receives honoraria from Johnson & Johnson and Bayer and advisory board fees from Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, and Sanofi-Aventis. Dr Hankey receives honoraria from Johnson & Johnson, Bayer, and Sanofi-Aventis and serves on trial adjudication committees and an advisory board for Boehringer Ingelheim. Dr Hacke receives honoraria from Johnson & Johnson and Bayer and serves on an advisory board to Boehringer Ingelheim. Dr Becker receives research support from Bayer and Johnson & Johnson. Dr Nessel is an employee of Johnson & Johnson. Dr Fox receives research grants and honoraria from Bayer, Lilly, Boehringer Ingelheim, Sanofi-Aventis, and GlaxoSmithKline. Dr Califf receives consulting fees and research funding from Johnson & Johnson. A full list of Drs Piccini, Patel, Mahaffey, and Califf's disclosures are listed at www.dcri.org. The remaining authors report no conflicts. NR 22 TC 168 Z9 173 U1 4 U2 42 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 15 PY 2013 VL 127 IS 2 BP 224 EP + DI 10.1161/CIRCULATIONAHA.112.107128 PG 13 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 071ZL UT WOS:000313637200019 PM 23212720 ER PT J AU Posfai, M Liu, YY Slotine, JJ Barabasi, AL AF Posfai, Marton Liu, Yang-Yu Slotine, Jean-Jacques Barabasi, Albert-Laszlo TI Effect of correlations on network controllability SO SCIENTIFIC REPORTS LA English DT Article ID COMPLEX NETWORKS; DYNAMICS AB A dynamical system is controllable if by imposing appropriate external signals on a subset of its nodes, it can be driven from any initial state to any desired state in finite time. Here we study the impact of various network characteristics on the minimal number of driver nodes required to control a network. We find that clustering and modularity have no discernible impact, but the symmetries of the underlying matching problem can produce linear, quadratic or no dependence on degree correlation coefficients, depending on the nature of the underlying correlations. The results are supported by numerical simulations and help narrow the observed gap between the predicted and the observed number of driver nodes in real networks. C1 [Posfai, Marton; Liu, Yang-Yu; Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. [Posfai, Marton; Liu, Yang-Yu; Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Posfai, Marton] Eotvos Lorand Univ, Dept Phys Complex Syst, Budapest, Hungary. [Posfai, Marton] Budapest Univ Technol & Econ, Dept Theoret Phys, Budapest, Hungary. [Liu, Yang-Yu] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Slotine, Jean-Jacques] MIT, Dept Mech Engn, Nonlinear Syst Lab, Cambridge, MA 02139 USA. [Slotine, Jean-Jacques] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Barabasi, Albert-Laszlo] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA USA. [Posfai, Marton; Barabasi, Albert-Laszlo] Cent European Univ, Ctr Network Sci, Budapest, Hungary. RP Barabasi, AL (reprint author), Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. EM alb@neu.edu RI Liu, Yang-Yu/G-8885-2011 OI Liu, Yang-Yu/0000-0003-2728-4907 FU Network Science Collaborative Technology Alliance; US Army Research Laboratory [W911NF-09-2-0053]; Defense Advanced Research Projects Agency [11645021]; Defense Threat Reduction Agency award WMD [BRBAA07-J-2-0035]; FET IP project MULTIPLEX [3A532]; European Union Seventh Framework Programme (FP7) [270833] FX This work was supported by the Network Science Collaborative Technology Alliance sponsored by the US Army Research Laboratory under Agreement Number W911NF-09-2-0053; the Defense Advanced Research Projects Agency under Agreement Number 11645021; the Defense Threat Reduction Agency award WMD BRBAA07-J-2-0035; FET IP project MULTIPLEX (3A532) and the generous support of Lockheed Martin. M. Posfai has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement No. 270833. NR 44 TC 53 Z9 53 U1 2 U2 67 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 15 PY 2013 VL 3 AR 1067 DI 10.1038/srep01067 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 070YO UT WOS:000313551000001 PM 23323210 ER PT J AU Manchikanti, L Pampati, V Falco, FJE Hirsch, JA AF Manchikanti, Laxmaiah Pampati, Vidyasagar Falco, Frank J. E. Hirsch, Joshua A. TI Growth of Spinal Interventional Pain Management Techniques Analysis of Utilization Trends and Medicare Expenditures 2000 to 2008 SO SPINE LA English DT Article DE chronic spinal pain; spinal interventional techniques; interventional pain management; ambulatory surgery centers; hospital outpatient departments; Medicare ID LOW-BACK-PAIN; CAUDAL EPIDURAL INJECTIONS; ACTIVE-CONTROLLED-TRIAL; DOUBLE-BLIND TRIAL; CLINICAL-PRACTICE GUIDELINES; RANDOMIZED DOUBLE-BLIND; LUMBAR DISC HERNIATION; CHRONIC NONCANCER PAIN; CHRONIC THORACIC PAIN; MEDIAL BRANCH BLOCKS AB Study Design. Analysis of the growth, utilization trends, and Medicare expenditures of spinal interventional pain management techniques from 2000 through 2008. Objective. To evaluate the use of epidural steroid injections, facet joint interventions, and sacroiliac joint interventions, and to analyze the trends of Medicare utilization and expenditures in multiple settings-namely, hospital outpatient departments, ambulatory surgery centers, and physician offices. Summary of Background Data. There has been an explosive growth of many invasive and noninvasive modalities designed to manage chronic spinal pain. Commonly used interventional techniques include epidural steroid injections, facet joint interventions, and sacroiliac joint interventions. However, their effectiveness and the appropriateness of their application continue to be debated. Methods. The present article provides an analysis of the growth of spinal interventional techniques, as described earlier, for managing the chronic spinal pain of Medicare beneficiaries from 2000 through 2008. The standard 5% national sample of the Centers for Medicare and Medicaid Services carrier claims that record data from 2000 through 2008 were utilized. Current procedural terminology codes from 2000 through 2008 were used to identify the number of procedures performed each year, as well as trends and expenditures. Results. Medicare recipients receiving spinal interventional techniques increased 107.8% from 2000 through 2008, with an annual average increase of 9.6%, whereas spinal interventional techniques increased 186.8%, an annual average increase of 14.1% per 100,000 beneficiaries. Conclusion. The study suggests explosive increases in spinal interventional techniques from 2000 to 2008, with some slowing of growth in later years. C1 [Manchikanti, Laxmaiah; Pampati, Vidyasagar] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Falco, Frank J. E.] Mid Atlantic Spine & Pain Phys Newark, Newark, DE USA. [Falco, Frank J. E.] Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. [Hirsch, Joshua A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. [Hirsch, Joshua A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com FU American Society of Interventional Pain Physicians FX American Society of Interventional Pain Physicians funds were received to support this work. NR 70 TC 47 Z9 48 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD JAN 15 PY 2013 VL 38 IS 2 BP 157 EP 168 DI 10.1097/BRS.0b013e318267f463 PG 12 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 070YN UT WOS:000313550900018 PM 22781007 ER PT J AU Keating, NL Kouri, EM He, YL West, DW Winer, EP AF Keating, Nancy L. Kouri, Elena M. He, Yulei West, Dee W. Winer, Eric P. TI Effect of Massachusetts health insurance reform on mammography use and breast cancer stage at diagnosis SO CANCER LA English DT Article DE health care reform; insurance; mammography; breast cancer ID SERVICES TASK-FORCE; UPDATE; ACCESS; CARE; ASSOCIATION; DISPARITIES; COVERAGE; OUTCOMES; ADULTS; WOMEN AB BACKGROUND: Massachusetts law requires all residents to maintain a minimum level of health insurance, and rates of uninsurance in that state decreased from 6.4% in 2006 to 1.9% in 2010. The authors of this report assessed whether health insurance expansion was associated with use of mammography and earlier stage at breast cancer diagnosis. METHODS: By using a prereform/postreform design with a concurrent control (California), mammography rates in the last year were assessed using the Behavioral Risk Factor Surveillance System survey and the diagnosis of stage I (vs II/III/IV) breast cancers based on cancer registry data among women ages 41 to 64. Propensity score analyses were used to compare California women who were most similar to women in Massachusetts with Massachusetts women. RESULTS: Among propensity-weighted cohorts, adjusted mammography rates in Massachusetts were 69.2% in 2006, 69.5% in 2008, and 69.0% in 2010. In California, the rates were 59% in 2006, 60.3% in 2008, and 56.2% in 2010 (P = .89 for interaction by state for 2010 vs 2006). Among propensity-weighted cohorts, adjusted rates of diagnosis with stage I cancers were 52.2% in 2006, 53.5% in 2007, and 52.4% in 2008 in Massachusetts versus 46.4% in 2006, 46.3% in 2007, and 45.7% in 2008 in California (P = .58 for interaction by state for 2010 vs 2006). CONCLUSIONS: Health insurance reform in Massachusetts was not associated with increased rates of mammography or earlier stage at diagnosis compared with California, possibly because of insurance and mammography rates that already were high. Additional research is needed to assess the impact of insurance expansions in other populations, especially those with higher uninsurance rates. Cancer 2013. (c) 2012 American Cancer Society. C1 [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. [Keating, Nancy L.; Kouri, Elena M.; He, Yulei] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [West, Dee W.] Canc Prevent Inst Calif, Fremont, CA USA. [Winer, Eric P.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. EM keating@hcp.med.harvard.edu FU American Cancer Society [RSGI-09-269-01-CPHPS] FX This work was supported by Research Scholar Grant RSGI-09-269-01-CPHPS from the American Cancer Society. NR 32 TC 10 Z9 10 U1 1 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JAN 15 PY 2013 VL 119 IS 2 BP 250 EP 258 DI 10.1002/cncr.27757 PG 9 WC Oncology SC Oncology GA 068KL UT WOS:000313365500004 PM 22833148 ER PT J AU Gao, L Faibish, D Fredman, G Herrera, BS Chiang, N Serhan, CN Van Dyke, TE Gyurko, R AF Gao, Li Faibish, Dan Fredman, Gabrielle Herrera, Bruno S. Chiang, Nan Serhan, Charles N. Van Dyke, Thomas E. Gyurko, Robert TI Resolvin E1 and Chemokine-like Receptor 1 Mediate Bone Preservation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PRORESOLVING LIPID MEDIATORS; OSTEOCLAST DIFFERENTIATION; IN-VITRO; INFLAMMATION; RESOLUTION; CELLS; CHEMERIN; IDENTIFICATION; PERIODONTITIS; PATHOGENESIS AB The polyunsaturated v-3 fatty acid eicosapentaenoic acid-derived resolvin E1 (RvE1) enhances resolution of inflammation, prevents bone loss, and induces bone regeneration. Although the inflammation-resolving actions of RvE1 are characterized, the molecular mechanism of its bone-protective actions are of interest. To test the hypothesis that receptor-mediated events impact bone changes, we prepared transgenic mice overexpressing the RvE1 receptor chemokine-like receptor 1 (chemR23) on leukocytes. In zymosan-initiated peritonitis, neutrophil polymorphonuclear leukocyte infiltration in response to RvE1 was limited requiring log order lower doses in chemR23tg mice. Ligature-induced alveolar bone loss was diminished in chemR23tg mice. Local RvE1 treatment of uniform craniotomy in the parietal bone significantly accelerated regeneration of the bone defect. In in vitro bone cultures, RvE1 significantly enhanced expression of osteoprotegerin (OPG) without inducing change in receptor activator of NF-kappa B ligand levels, whereas the osteogenic markers alkaline phosphatase, bone sialoprotein, and Runt-related transcription factor 2 remained unchanged. These results indicate that RvE1 modulates osteoclast differentiation and bone remodeling by direct actions on bone, rescuing OPG production and restoring a favorable receptor activator of NF-kB ligand/OPG ratio, in addition to known anti-inflammatory and proresolving actions. The Journal of Immunology, 2013, 190: 689-694. C1 [Gao, Li; Faibish, Dan; Fredman, Gabrielle; Gyurko, Robert] Boston Univ, Goldman Sch Dent Med, Boston, MA 02118 USA. [Herrera, Bruno S.; Van Dyke, Thomas E.] Forsyth Inst, Cambridge, MA 02142 USA. [Chiang, Nan; Serhan, Charles N.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02215 USA. RP Gyurko, R (reprint author), Boston Univ, Goldman Sch Dent Med, 100 E Newton St,Room 217, Boston, MA 02118 USA. EM gyurko@bu.edu OI Gyurko, Robert/0000-0003-1457-6812 FU U.S. Public Health Service [DE19938, DE16933, DE16191] FX This work was supported in part by U.S. Public Health Service Grants DE19938, DE16933, and DE16191. NR 41 TC 25 Z9 26 U1 0 U2 11 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2013 VL 190 IS 2 BP 689 EP 694 DI 10.4049/jimmunol.1103688 PG 6 WC Immunology SC Immunology GA 068KM UT WOS:000313365600021 PM 23241890 ER PT J AU Metra, M Cotter, G Davison, BA Felker, GM Filippatos, G Greenberg, BH Ponikowski, P Unemori, E Voors, AA Adams, KF Dorobantu, MI Grinfeld, L Jondeau, G Marmor, A Masip, J Pang, PS Werdan, K Prescott, MF Edwards, C Teichman, SL Trapani, A Bush, CA Saini, R Schumacher, C Severin, T Teerlink, JR AF Metra, Marco Cotter, Gad Davison, Beth A. Felker, G. Michael Filippatos, Gerasimos Greenberg, Barry H. Ponikowski, Piotr Unemori, Elaine Voors, Adriaan A. Adams, Kirkwood F., Jr. Dorobantu, Maria I. Grinfeld, Liliana Jondeau, Guillaume Marmor, Alon Masip, Josep Pang, Peter S. Werdan, Karl Prescott, Margaret F. Edwards, Christopher Teichman, Sam L. Trapani, Angelo Bush, Christopher A. Saini, Rajnish Schumacher, Christoph Severin, Thomas Teerlink, John R. CA RELAX-AHF Investigators TI Effect of Serelaxin on Cardiac, Renal, and Hepatic Biomarkers in the Relaxin in Acute Heart Failure (RELAX-AHF) Development Program Correlation With Outcomes SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE congestion; heart failure; organ protection; RELAX-AHF; serelaxin ID 3RD UNIVERSAL DEFINITION; MYOCARDIAL-INFARCTION; TROPONIN ELEVATION; EUROPEAN-SOCIETY; TASK-FORCE; ASSOCIATION; HOSPITALIZATION; PROTECT; CARE; PREVALENCE AB Objectives The aim of this study was to assess the effects of serelaxin on short-term changes in markers of organ damage and congestion and relate them to 180-day mortality in patients with acute heart failure. Background Hospitalization for acute heart failure is associated with high post-discharge mortality, and this may be related to organ damage. Methods The Pre-RELAX-AHF (Relaxin in Acute Heart Failure) phase II study and RELAX-AHF phase III study were international, multicenter, double-blind, placebo-controlled trials in which patients hospitalized for acute heart failure were randomized within 16 h to intravenous placebo or serelaxin. Each patient was followed daily to day 5 or discharge and at days 5, 14, and 60 after enrollment. Vital status was assessed through 180 days. In RELAX-AHF, laboratory evaluations were performed daily to day 5 and at day 14. Plasma levels of biomarkers were measured at baseline and days 2, 5, and 14. All-cause mortality was assessed as a safety endpoint in both studies. Results Serelaxin reduced 180-day mortality, with similar effects in the phase II and phase III studies (combined studies: N = 1,395; hazard ratio: 0.62; 95% confidence interval: 0.43 to 0.88; p = 0.0076). In RELAX-AHF, changes in markers of cardiac (high-sensitivity cardiac troponin T), renal (creatinine and cystatin-C), and hepatic (aspartate transaminase and alanine transaminase) damage and of decongestion (N-terminal pro-brain natriuretic peptide) at day 2 and worsening heart failure during admission were associated with 180-day mortality. Serelaxin administration improved these markers, consistent with the prevention of organ damage and faster decongestion. Conclusions Early administration of serelaxin was associated with a reduction of 180-day mortality, and this occurred with fewer signs of organ damage and more rapid relief of congestion during the first days after admission. (J Am Coll Cardiol 2013; 61: 196-206) (C) 2013 by the American College of Cardiology Foundation C1 [Metra, Marco] Univ Brescia, Dept Med & Surg Specialties Radiol Sci & Publ Hlt, Brescia, Italy. [Metra, Marco] Spedali Civil Brescia, I-25123 Brescia, Italy. [Cotter, Gad; Davison, Beth A.; Edwards, Christopher] Momentum Res Inc, Durham, NC USA. [Felker, G. Michael] Duke Univ, Sch Med, Durham, NC USA. [Felker, G. Michael] Duke Univ, Med Ctr, Duke Heart Ctr, Durham, NC 27710 USA. [Filippatos, Gerasimos] Athens Univ Hosp, Athens, Greece. [Greenberg, Barry H.] Univ Calif San Diego, San Diego, CA 92103 USA. [Ponikowski, Piotr] Med Univ, Clin Mil Hosp, Wroclaw, Poland. [Unemori, Elaine; Teichman, Sam L.] Corthera Inc, San Carlos, CA USA. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [Adams, Kirkwood F., Jr.] Univ N Carolina, Chapel Hill, NC USA. [Dorobantu, Maria I.] Floreasca Emergency Clin Hosp, Bucharest, Romania. [Grinfeld, Liliana] Univ Buenos Aires, Sch Med, Cardiovasc Physiopathol Inst, Buenos Aires, DF, Argentina. [Jondeau, Guillaume] Univ Paris 07, Hop Bichat, Paris, France. [Marmor, Alon] Ziv Med Ctr, Safed, Israel. [Masip, Josep] Univ Barcelona, Consorci Sanitari Integral, Barcelona, Spain. [Pang, Peter S.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Werdan, Karl] Univ Halle Wittenberg, D-06108 Halle, Germany. [Prescott, Margaret F.; Trapani, Angelo; Bush, Christopher A.; Saini, Rajnish] Novartis Pharmaceut, E Hanover, NJ USA. [Schumacher, Christoph; Severin, Thomas] Novartis Pharma AG, Basel, Switzerland. [Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Metra, M (reprint author), Spedali Civil Brescia, Piazza Spedali Civili 1, I-25123 Brescia, Italy. EM metramarco@libero.it RI Lainscak, Mitja/F-3237-2015; Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Metra, Marco/0000-0001-6691-8568; Davison, Beth/0000-0003-2374-6449 FU Corthera, Inc. (a Novartis AG affiliate company); Novartis; Amgen; Corthera; Merck; Roche Diagnostics; Duke Clinical Research Unit; Momentum Research; Medpace; Otsuka; Trevena; BG Medicine; NHLBI; Nanosphere; European Union; Abbott Vascular; Bayer; Abbott; PDL BioPharma; Cardio3 Bioscience; Cytokinetics; Takeda; Teva; Alere; Cardio3Biosciences; Celladon; Ceva; European Commission; Dutch Heart Foundation; Servier; Torrent; Vifor FX The Relaxin in Acute Heart Failure study is supported by Corthera, Inc. (a Novartis AG affiliate company). Dr. Adams has received research grants from Novartis, Amgen, Corthera, Merck, Roche Diagnostics, and the Duke Clinical Research Unit and has received consulting fees from Corthera, Merck, Roche Diagnostics, the Duke Clinical Research Unit, and Momentum Research. Dr. Felker has received consulting income from Novartis, Medpace, Amgen, Otsuka, Trevena, Roche Diagnostics, Merck, BG Medicine, Medtronic, and St Jude and grant funding from Amgen, Otsuka, Roche Diagnostics, and NHLBI. Dr. Filippatos is a consultant to Corthera, Bayer, Cardiorentis, and has received research grants from Amgen, Nanosphere, European Union. Dr. Greenberg served as a consultant for Corthera and Novartis. Dr. Metra has received consulting income from Abbott Vascular, Bayer, Corthera, and Novartis, and travel support and honoraria from Servier and Novartis. Dr. Ponikowski was a consultant for Astellas, Bayer, EKR Therapeutics, J&J, the Medicines Company, Medtronic, Novartis, Otsuka, Palatin Technologies, PDL BioPharma, Pericor Therapeutics, SigmaTau, Solvay Pharmaceuticals, and Trevena; has received honoraria from Alere, Beckman-Coulter, BiogenIdec, Corthera, Ikaria, Nile Therapeutics, Momentum Research, and Overcome; has received research support from Abbott, Merck and PDL BioPharma; and has received travel support from MyLife and equipment support from Sonosite. Dr. Teerlink has received research grants or consulting fees from Amgen, Bayer, Corthera, Cardio3 Bioscience, Cytokinetics, Merck, Novartis, Takeda, Teva and Trevena. Dr. Dorobantu, Grinfeld, Joundeau, Marmor, Masip and Verdan have received research grants from Corthera (a Novartis affiliate company). Dr. Unemori is employed and Dr. Teichman was employed by the sponsor, Corthera. Drs. Bush, Prescott, Saini, and Trapani are employees and shareholders of Novartis Pharmaceuticals Corporation. Drs. Schumacher and Severin are employees and shareholders of Novartis Pharma AG. Drs. Davison and Cotter and Mr. Edwards are employees of Momentum Research, which has provided consulting and trial management services to NovaCardia, Merck, Corthera, Novartis, Nile Therapeutics, Bioheart, Cardio3 Biosciences, Amgen, Celadon, Targegen, Trevena, Sorbent Therapeutics, and NIH. Dr. Pang has been consultant for Astellas, Bayer, EKR Therapeutics, J& J, the Medicines Company, Medtronic, Novartis, Otsuka, Palatin Technologies, PDL BioPharma, Pericor Therapeutics, SigmaTau, Solvay Pharmaceuticals, Trevena and has received honoraria from Alere, Beckman-Coulter, BiogenIdec, Corthera, Ikaria, Nile Therapeutics, Momentum Research, Overcome and research support from Abbott, Merck and PDL BioPharma, travel support from MyLife and equipment support from Sonosite. Dr. Voorshas received consultancy fees and/or research grants from Alere, Bayer, Cardio3Biosciences, Celladon, Ceva, European Commission, Dutch Heart Foundation, Novartis, Servier, Torrent, and Vifor. Dr. Werdan received honorarium for patient enrolment and for national coordinatorship of RELAX-AHF trial and received honoraria for lectures from Servier, Biotest, Maquet, Brahms Company. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 39 TC 163 Z9 168 U1 2 U2 23 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 15 PY 2013 VL 61 IS 2 BP 196 EP 206 DI 10.1016/j.jacc.2012.11.005 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 065PZ UT WOS:000313162200015 PM 23273292 ER PT J AU Holland, JP Jones, MW Cohrs, S Schibli, R Fischer, E AF Holland, Jason P. Jones, Michael W. Cohrs, Susan Schibli, Roger Fischer, Eliane TI Fluorinated quinazolinones as potential radiotracers for imaging kinesin spindle protein expression SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE Quinazolinone; Kinesin spindle protein; Mitosis; Fluorine; Allosteric inhibitors ID X-RAY-DIFFRACTION; ABSOLUTE-CONFIGURATION; SMALL-MOLECULE; INHIBITOR; MECHANISM; EG5; ISPINESIB; MONASTROL; MITOSIS; KSP AB Anti-mitotic anti-cancer drugs offer a potential platform for developing new radiotracers for imaging proliferation markers associated with the mitosis-phase of the cell-cycle. One interesting target is kinesin spindle protein (KSP)-an ATP-dependent motor protein that plays a vital role in bipolar spindle formation. In this work we synthesised a range of new fluorinated-quinazolinone compounds based on the structure of the clinical candidate KSP inhibitor, ispinesib, and investigated their properties in vitro as potential anti-mitotic agents targeting KSP expression. Anti-proliferation (MTT and BrdU) assays combined with additional studies including fluorescence-assisted cell sorting (FACS) analysis of cell-cycle arrest confirmed the mechanism and potency of these biphenyl compounds in a range of human cancer cell lines. Additional studies using confocal fluorescence microscopy showed that these compounds induce M-phase arrest via monoaster spindle formation. Structural studies revealed that compound 20-(R) is the most potent fluorinated-quinazolinone inhibitor of KSP and represents a suitable lead candidate for further studies on designing F-18-radiolabelled agents for positron-emission tomography (PET). (C) 2012 Elsevier Ltd. All rights reserved. C1 [Holland, Jason P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Holland, Jason P.; Schibli, Roger] ETH, Inst Pharmaceut Sci, CH-8093 Zurich, Switzerland. [Jones, Michael W.] Univ Oxford, Dept Chem, Chem Res Lab, Oxford OX1 3TA, England. [Cohrs, Susan; Schibli, Roger; Fischer, Eliane] Paul Scherrer Inst, Ctr Radiopharmaceut Sci, Villigen, Switzerland. RP Holland, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Nucl Med & Mol Imaging, 55 Fruit St,White 427, Boston, MA 02114 USA. EM holland.jason@mgh.harvard.edu; eliane.fischer@psi.ch RI Fischer, Eliane/M-2590-2013; OI Fischer, Eliane/0000-0002-3399-3737; Holland, Jason/0000-0002-0066-219X; Schibli, Roger/0000-0002-1537-3833 FU ETH Fellowship Program [FEL-01-10-1] FX Funded in part by the ETH Fellowship Program (FEL-01-10-1; JPH). We thank Dr. NagaVaraKishore Pillarsetty, Dr. Aristeidis Chiotellis, Dr. Selena Melicevic Sephton and Cindy Fischer for helpful discussions and advice regarding chemical synthesis and chromatography. We also thank Dr. Tobias Schwarz and Dr. Joaquim Hehl at the Light Microscopy Centre, ETH Zurich for technical support regarding fluorescence microscopy studies. NR 27 TC 6 Z9 6 U1 0 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JAN 15 PY 2013 VL 21 IS 2 BP 496 EP 507 DI 10.1016/j.bmc.2012.11.013 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 063OG UT WOS:000313008800013 PM 23245569 ER PT J AU Barsic, B Dickerman, S Krajinovic, V Pappas, P Altclas, J Carosi, G Casabe, JH Chu, VH Delahaye, F Edathodu, J Fortes, CQ Olaison, L Pangercic, A Patel, M Rudez, I Tamin, SS Vincelj, J Bayer, AS Wang, A AF Barsic, Bruno Dickerman, Stuart Krajinovic, Vladimir Pappas, Paul Altclas, Javier Carosi, Giampiero Casabe, Jose H. Chu, Vivian H. Delahaye, Francois Edathodu, Jameela Fortes, Claudio Querido Olaison, Lars Pangercic, Ana Patel, Mukesh Rudez, Igor Tamin, Syahidah Syed Vincelj, Josip Bayer, Arnold S. Wang, Andrew CA Int Collaboration Endocarditis-Pro TI Influence of the Timing of Cardiac Surgery on the Outcome of Patients With Infective Endocarditis and Stroke SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE endocarditis; stroke; surgery ID CEREBROVASCULAR COMPLICATIONS; NEUROLOGIC COMPLICATIONS; PROSPECTIVE MULTICENTER; BACTERIAL-ENDOCARDITIS; CARDIOEMBOLIC STROKE; VALVE-REPLACEMENT; PROGNOSTIC VALUE; BRAIN-DAMAGE; DIAGNOSIS; ECHOCARDIOGRAPHY AB Background. The timing of cardiac surgery after stroke in infective endocarditis (IE) remains controversial. We examined the relationship between the timing of surgery after stroke and the incidence of in-hospital and 1-year mortalities. Methods. Data were obtained from the International Collaboration on Endocarditis-Prospective Cohort Study of 4794 patients with definite IE who were admitted to 64 centers from June 2000 through December 2006. Multivariate logistic regression and Cox regression analyses were performed to estimate the impact of early surgery on hospital and 1-year mortality after adjustments for other significant covariates. Results. Of the 857 patients with IE complicated by ischemic stroke syndromes, 198 who underwent valve replacement surgery poststroke were available for analysis. Overall, 58 (29.3%) patients underwent early surgical treatment vs 140 (70.7%) patients who underwent late surgical treatment. After adjustment for other risk factors, early surgery was not significantly associated with increased in-hospital mortality rates (odds ratio, 2.308; 95% confidence interval [CI], .942-5.652). Overall, probability of death after 1-year follow-up did not differ between 2 treatment groups (27.1% in early surgery and 19.2% in late surgery group, P = .328; adjusted hazard ratio, 1.138; 95% CI, .802-1.650). Conclusions. There is no apparent survival benefit in delaying surgery when indicated in IE patients after ischemic stroke. Further observational analyses that include detailed pre- and postoperative clinical neurologic findings and advanced imaging data (eg, ischemic stroke size), may allow for more refined recommendations on the optimal timing of valvular surgery in patients with IE and recent stroke syndromes. C1 [Barsic, Bruno; Krajinovic, Vladimir] Hosp Infect Dis, Sch Med, Zagreb, Croatia. [Dickerman, Stuart] NYU, Sch Med, New York, NY USA. [Pappas, Paul; Chu, Vivian H.; Wang, Andrew] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Altclas, Javier] Barcelona Ctr Int Hlth Res, Barcelona, Spain. [Carosi, Giampiero] Univ Brescia, I-25121 Brescia, Italy. [Casabe, Jose H.] Fdn Favaloro, Buenos Aires, DF, Argentina. [Delahaye, Francois] Hop Louis Pradel, Lyon, France. [Edathodu, Jameela] King Faisal Specialist Hosp & Res Ctr, Riyadh 11211, Saudi Arabia. [Fortes, Claudio Querido] Clementino Fraga Filho Hosp, Rio De Janeiro, Brazil. [Olaison, Lars] Sahlgrens Univ Hosp, Gothenburg, Sweden. [Pangercic, Ana] Univ Hosp Ctr Sestre Milosrdnice, Zagreb, Croatia. [Patel, Mukesh] Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Rudez, Igor; Vincelj, Josip] Dubrava Univ Hosp, Zagreb, Croatia. [Tamin, Syahidah Syed] Inst Jantung Negara, Kuala Lumpur, Malaysia. [Bayer, Arnold S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Barsic, B (reprint author), Hosp Infect Dis, Sch Med, Zagreb, Croatia. EM bbarsic@bfm.hr RI Toniolo, Antonio/B-4103-2015; Bouza, Emilio/D-8661-2014; OI Toniolo, Antonio/0000-0003-3008-2126; Bouza, Emilio/0000-0001-6967-9267; Vincelj, Josip/0000-0003-0064-9128; Athan, Eugene/0000-0001-9838-6471; Munoz Garcia, Patricia Carmen/0000-0001-5706-5583; Sfeir, Jad/0000-0003-1576-1534; Falces, Carlos/0000-0002-3483-3786; Selton-Suty, Christine/0000-0003-4129-5784; Post, Jeffrey/0000-0003-1475-9272 FU Cubist; Astellas; Polymedix Inc; Trius; Duke University Center; Gilead Sciences; Edward Lifesciences; Abbott Vascular FX B. B. is a consultant for Pfizer and Pliva Pharmaceuticals and has also participated as a speaker for MSD, Pfizer, and Pliva. A. S. B. has received grants from Cubist, Astellas, Polymedix Inc, and Trius, and is receiving payments for lectures from Duke University Center (ID Grand Rounds). A. W. has provided expert testimony for Young Moore and Henderson, has received grants from Gilead Sciences, Edward Lifesciences, and Abbott Vascular, and has received honoraria from American Physician, Springer, and the American College of Cardiology Foundation. All other authors report no potential conflicts. NR 31 TC 39 Z9 43 U1 1 U2 15 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 15 PY 2013 VL 56 IS 2 BP 209 EP 217 DI 10.1093/cid/cis878 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 058AJ UT WOS:000312606100011 PM 23074311 ER PT J AU Hirsch, MS AF Hirsch, Martin S. TI Editorial Comment Regarding H5N1 Influenza Article in This Issue SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material C1 [Hirsch, Martin S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hirsch, MS (reprint author), 65 Landsdowne St,Room 419, Cambridge, MA 02139 USA. EM mshirsch@partners.org NR 3 TC 4 Z9 4 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 15 PY 2013 VL 207 IS 2 BP 207 EP 207 DI 10.1093/infdis/jis528 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 061YO UT WOS:000312886400003 PM 23042759 ER PT J AU Tait, BD Susal, C Gebel, HM Nickerson, PW Zachary, AA Claas, FHJ Reed, EF Bray, RA Campbell, P Chapman, JR Coates, PT Colvin, RB Cozzi, E Doxiadis, IIN Fuggle, SV Gill, J Glotz, D Lachmann, N Mohanakumar, T Suciu-Foca, N Sumitran-Holgersson, S Tanabe, K Taylor, CJ Tyan, DB Webster, A Zeevi, A Opelz, G AF Tait, Brian D. Suesal, Caner Gebel, Howard M. Nickerson, Peter W. Zachary, Andrea A. Claas, Frans H. J. Reed, Elaine F. Bray, Robert A. Campbell, Patricia Chapman, Jeremy R. Coates, P. Toby Colvin, Robert B. Cozzi, Emanuele Doxiadis, Ilias I. N. Fuggle, Susan V. Gill, John Glotz, Denis Lachmann, Nils Mohanakumar, Thalachallour Suciu-Foca, Nicole Sumitran-Holgersson, Suchitra Tanabe, Kazunari Taylor, Craig J. Tyan, Dolly B. Webster, Angela Zeevi, Adriana Opelz, Gerhard TI Consensus Guidelines on the Testing and Clinical Management Issues Associated With HLA and Non-HLA Antibodies in Transplantation SO TRANSPLANTATION LA English DT Article DE Transplantation; HLA; Antibodies ID HUMAN-LEUKOCYTE ANTIGEN; DONOR-SPECIFIC ANTIBODIES; RENAL-ALLOGRAFT REJECTION; ANTIENDOTHELIAL CELL ANTIBODIES; POSITIVE CROSS-MATCH; INCOMPATIBLE KIDNEY-TRANSPLANTATION; CORONARY-ARTERY-DISEASE; PREFORMED LYMPHOCYTOTOXIC ANTIBODIES; PEDIATRIC CARDIAC TRANSPLANTATION; BRONCHIOLITIS OBLITERANS SYNDROME AB Background. The introduction of solid-phase immunoassay (SPI) technology for the detection and characterization of human leukocyte antigen (HLA) antibodies in transplantation while providing greater sensitivity than was obtainable by complement-dependent lymphocytotoxicity (CDC) assays has resulted in a new paradigm with respect to the interpretation of donor-specific antibodies (DSA). Although the SPI assay performed on the Luminex instrument (hereafter referred to as the Luminex assay), in particular, has permitted the detection of antibodies not detectable by CDC, the clinical significance of these antibodies is incompletely understood. Nevertheless, the detection of these antibodies has led to changes in the clinical management of sensitized patients. In addition, SPI testing raises technical issues that require resolution and careful consideration when interpreting antibody results. Methods. With this background, The Transplantation Society convened a group of laboratory and clinical experts in the field of transplantation to prepare a consensus report and make recommendations on the use of this new technology based on both published evidence and expert opinion. Three working groups were formed to address (a) the technical issues with respect to the use of this technology, (b) the interpretation of pretransplantation antibody testing in the context of various clinical settings and organ transplant types (kidney, heart, lung, liver, pancreas, intestinal, and islet cells), and (c) the application of antibody testing in the posttransplantation setting. The three groups were established in November 2011 and convened for a "Consensus Conference on Antibodies in Transplantation" in Rome, Italy, in May 2012. The deliberations of the three groups meeting independently and then together are the bases for this report. Results. A comprehensive list of recommendations was prepared by each group. A summary of the key recommendations follows. Technical Group: (a) SPI must be used for the detection of pretransplantation HLA antibodies in solid organ transplant recipients and, in particular, the use of the single-antigen bead assay to detect antibodies to HLA loci, such as Cw, DQA, DPA, and DPB, which are not readily detected by other methods. (b) The use of SPI for antibody detection should be supplemented with cell-based assays to examine the correlations between the two types of assays and to establish the likelihood of a positive crossmatch (XM). (c) There must be an awareness of the technical factors that can influence the results and their clinical interpretation when using the Luminex bead technology, such as variation in antigen density and the presence of denatured antigen on the beads. Pretransplantation Group: (a) Risk categories should be established based on the antibody and the XM results obtained. (b) DSA detected by CDC and a positive XM should be avoided due to their strong association with antibody-mediated rejection and graft loss. (c) A renal transplantation can be performed in the absence of a prospective XM if single-antigen bead screening for antibodies to all class I and II HLA loci is negative. This decision, however, needs to be taken in agreement with local clinical programs and the relevant regulatory bodies. (d) The presence of DSA HLA antibodies should be avoided in heart and lung transplantation and considered a risk factor for liver, intestinal, and islet cell transplantation. Posttransplantation Group: (a) High-risk patients (i.e., desensitized or DSA positive/XM negative) should be monitored by measurement of DSA and protocol biopsies in the first 3 months after transplantation. (b) Intermediate-risk patients (history of DSA but currently negative) should be monitored for DSA within the first month. If DSA is present, a biopsy should be performed. (c) Low-risk patients (nonsensitized first transplantation) should be screened for DSA at least once 3 to 12 months after transplantation. If DSA is detected, a biopsy should be performed. In all three categories, the recommendations for subsequent treatment are based on the biopsy results. Conclusions. A comprehensive list of recommendations is provided covering the technical and pretransplantation and posttransplantation monitoring of HLA antibodies in solid organ transplantation. The recommendations are intended to provide state-of-the-art guidance in the use and clinical application of recently developed methods for HLA antibody detection when used in conjunction with traditional methods. C1 [Suesal, Caner; Opelz, Gerhard] Heidelberg Univ, Inst Immunol, Dept Transplantat Immunol, D-69120 Heidelberg, Germany. [Tait, Brian D.] Australian Red Cross Blood Serv, Natl Transplant Serv, Melbourne, Vic, Australia. [Gebel, Howard M.; Bray, Robert A.] Emory Univ, Sch Med, Atlanta, GA USA. [Nickerson, Peter W.] Univ Manitoba, Fac Med, Winnipeg, MB, Canada. [Zachary, Andrea A.] Johns Hopkins Univ, Sch Med, Immunogenet Lab, Baltimore, MD USA. [Claas, Frans H. J.; Doxiadis, Ilias I. N.] Leiden Univ, Med Ctr, Dept Immunohaematol & Blood Transfus, Leiden, Netherlands. [Reed, Elaine F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, UCLA Immunogenet Ctr, Los Angeles, CA 90095 USA. [Campbell, Patricia] Univ Alberta, Dept Med, Edmonton, AB, Canada. [Campbell, Patricia] Univ Alberta, Dept Lab Med, Edmonton, AB, Canada. [Chapman, Jeremy R.; Webster, Angela] Univ Sydney, Westmead Hosp, Ctr Transplant & Renal Res, Sydney, NSW 2006, Australia. [Coates, P. Toby] Cent & No Adelaide Renal & Transplantat Serv, Adelaide, SA, Australia. [Colvin, Robert B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Cozzi, Emanuele] Univ Padua, Padua Med Ctr, Unit Clin & Expt Transplantat Immunol, Padua, Italy. [Fuggle, Susan V.] Oxford Univ Hosp NHS Trust, Oxford Transplant Ctr, Nuffield Dept Surg Sci, Oxford, England. [Gill, John] Univ British Columbia, Dept Med, Vancouver, BC, Canada. [Glotz, Denis] St Louis Hosp, Nephrol & Transplantat Dept, Paris, France. [Lachmann, Nils] Charite, HLA Lab, D-13353 Berlin, Germany. [Mohanakumar, Thalachallour] Washington Univ, Dept Surg, St Louis, MO USA. [Suciu-Foca, Nicole] Columbia Univ, Dept Pathol & Cell Biol, New York, NY USA. [Sumitran-Holgersson, Suchitra] Univ Gothenburg, Dept Surg, Gothenburg, Sweden. [Tanabe, Kazunari] Tokyo Womens Med Univ, Dept Urol, Tokyo, Japan. [Taylor, Craig J.] Cambridge Univ Hosp NHS Fdn Trust, Addenbrookes Hosp, Tissue Typing Lab, Cambridge, England. [Tyan, Dolly B.] Stanford Univ, Med Ctr, Dept Pathol, Histocompatibil Immunogenet & Dis Profiling Lab, Palo Alto, CA 94304 USA. [Zeevi, Adriana] Pittsburgh Med Ctr, Dept Pathol, Pittsburgh, PA USA. RP Opelz, G (reprint author), Heidelberg Univ, Inst Immunol, Dept Transplantat Immunol, Neuenheimer Feld 305, D-69120 Heidelberg, Germany. EM Gerhard.Opelz@med.uni-heidelberg.de OI Nickerson, Peter/0000-0002-7393-7799; Webster, Angela/0000-0001-7509-0512 FU Transplantation Society; Deutsche Gesellschaft fur Immungenetik; European Federation for Immunogenetics; British Society for Histocompatibility and Immunogenetics Association FX The members of the Antibody Consensus Group thank The Transplantation Society for initiating and financially supporting this exercise. Additional support was also provided by Deutsche Gesellschaft fur Immungenetik (G.O., C. S., and N.L.), The European Federation for Immunogenetics (F.H.J.C. and S. V. F.), and the British Society for Histocompatibility and Immunogenetics Association (C.J.T.). NR 276 TC 242 Z9 254 U1 1 U2 51 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN 15 PY 2013 VL 95 IS 1 BP 19 EP 47 DI 10.1097/TP.0b013e31827a19cc PG 29 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 064FT UT WOS:000313058700007 PM 23238534 ER PT J AU Daneshvar, K Nath, S Khan, A Shover, W Richardson, C Goodliffe, JM AF Daneshvar, Kaveh Nath, Sritama Khan, Abid Shover, Wesley Richardson, Christine Goodliffe, Julie M. TI MicroRNA miR-308 regulates dMyc through a negative feedback loop in Drosophila SO BIOLOGY OPEN LA English DT Article DE dMyc; miR-308; Drosophila melanogaster; Embryogenesis; Growth AB The abundance of Myc protein must be exquisitely controlled to avoid growth abnormalities caused by too much or too little Myc. An intriguing mode of regulation exists in which Myc protein itself leads to reduction in its abundance. We show here that dMyc binds to the miR-308 locus and increases its expression. Using our gain-of-function approach, we show that an increase in miR-308 causes a destabilization of dMyc mRNA and reduced dMyc protein levels. In vivo knockdown of miR-308 confirmed the regulation of dMyc levels in embryos. This regulatory loop is crucial for maintaining appropriate dMyc levels and normal development. Perturbation of the loop, either by elevated miR-308 or elevated dMyc, caused lethality. Combining elevated levels of both, therefore restoring balance between miR-308 and dMyc levels, resulted in lower apoptotic activity and suppression of lethality. These results reveal a sensitive feedback mechanism that is crucial to prevent the pathologies caused by abnormal levels of dMyc. (C) 2012. Published by The Company of Biologists Ltd. C1 [Daneshvar, Kaveh; Nath, Sritama; Khan, Abid; Shover, Wesley; Richardson, Christine; Goodliffe, Julie M.] Univ N Carolina, Dept Biol, Charlotte, NC 28223 USA. [Daneshvar, Kaveh] Harvard Univ, Gastrointestinal Unit, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Daneshvar, K (reprint author), Univ N Carolina, Dept Biol, Charlotte, NC 28223 USA. EM kdaneshvar@partners.org RI Daneshvar, Kaveh/M-9443-2014 OI Daneshvar, Kaveh/0000-0002-7863-0489 FU NIH (NCI) [1R15CA135481-01]; NSF ADVANCE grant FX We are thankful to Dr Cynthia Gibas and Dr Jennifer Weller of the UNC Charlotte Department of Bioinformatics and Genomics for training us and granting us access to the microarray core facility. We thank Dr Anthony Fodor and Dr Robert Reid for helping us with bioinformatics and microarray data analysis. We thank Mona Kashiha for helping us with graphical presentation of data. This work has been funded by the NIH (NCI, http://www.cancer.gov) to J.M.G., under grant number 1R15CA135481-01, and also by an NSF ADVANCE grant to UNC Charlotte. NR 54 TC 3 Z9 4 U1 0 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 2046-6390 J9 BIOL OPEN JI Biol. Open PD JAN 15 PY 2013 VL 2 IS 1 BP 1 EP 9 DI 10.1242/bio.20122725 PG 9 WC Biology SC Life Sciences & Biomedicine - Other Topics GA V36IK UT WOS:000209205800001 PM 23336071 ER PT J AU Case, BG Bertollo, DN Laska, EM Price, LH Siegel, CE Olfson, M Marcus, SC AF Case, Brady G. Bertollo, David N. Laska, Eugene M. Price, Lawrence H. Siegel, Carole E. Olfson, Mark Marcus, Steven C. TI Declining Use of Electroconvulsive Therapy in United States General Hospitals SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Electroconvulsive therapy (ECT); general hospitals; hospital psychiatry; mental health services; recurrent major depression; somatic therapy ID COMMUNITY HOSPITALS; ECT; DEPRESSION; ATTITUDES; PSYCHIATRISTS; EFFICACY; TRENDS AB Background: Falling duration of psychiatric inpatient stays over the past 2 decades and recent recommendations to tighten federal regulation of electroconvulsive therapy (ECT) devices have focused attention on trends in ECT use, but current national data have been unavailable. Methods: We calculated the annual number of inpatient stays involving ECT and proportion of general hospitals conducting the procedure at least once in the calendar year with a national sample of discharges from 1993 to 2009. We estimated adjusted probabilities that in patients with severe recurrent major depression (n = 465,646) were treated in a hospital that conducts ECT and, if so, received the procedure. Results: The annual number of stays involving ECT fell from 12.6 to 7.2/100,000 adult US residents, driven by dramatic declines among elderly persons, whereas the percentage of hospitals conducting ECT decreased from 14.8% to 10.6%. The percentage of stays for severe recurrent major depression in hospitals that conducted ECT fell from 70.5% to 44.7%, whereas receipt of ECT where conducted declined from 12.9% to 10.5%. For depressed inpatients, the adjusted probability that the treating hospital conducts ECT fell 34%, whereas probability of receiving ECT was unchanged for patients treated in facilities that conducted the procedure. Adjusted declines were greatest for elderly persons. Throughout the period inpatients from poorer neighborhoods or who were publicly insured or uninsured were less likely to receive care from hospitals conducting ECT. Conclusions: Electroconvulsive therapy use for severely depressed inpatients has fallen markedly, driven exclusively by a decline in the probability that their hospital conducts ECT. C1 [Case, Brady G.] Emma Pendleton Bradley Hosp, Hlth Serv Res Program, E Providence, RI 02915 USA. [Case, Brady G.; Price, Lawrence H.] Brown Univ, Dept Psychiat & Human Behav, Albert Med Sch, Providence, RI 02912 USA. [Price, Lawrence H.] Butler Hosp, Providence, RI 02906 USA. [Case, Brady G.; Bertollo, David N.; Laska, Eugene M.; Siegel, Carole E.] Nathan S Kline Inst Psychiat Res, Dept Stat, Orangeburg, NY 10962 USA. [Case, Brady G.; Bertollo, David N.; Laska, Eugene M.; Siegel, Carole E.] Nathan S Kline Inst Psychiat Res, Div Res Serv, Orangeburg, NY 10962 USA. [Case, Brady G.; Laska, Eugene M.; Siegel, Carole E.] NYU, Sch Med, Dept Psychiat, New York, NY 10003 USA. [Olfson, Mark] Columbia Univ, Coll Phys & Surg, New York State Psychiat Inst, New York, NY USA. [Marcus, Steven C.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Marcus, Steven C.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA. RP Case, BG (reprint author), Emma Pendleton Bradley Hosp, Hlth Serv Res Program, 1011 Vet Mem Pkwy, E Providence, RI 02915 USA. EM brady_case@brown.edu RI Case, Brady/M-1879-2015; OI Case, Brady/0000-0001-9512-0416; Laska, Eugene/0000-0001-6799-1361; Siegel, Carole/0000-0002-7460-788X FU Leon Levy Foundation; American Academy of Child and Adolescent Psychiatry Eli Lilly Pilot Research Award; American Psychiatric Association Astra Zeneca Young Mindsin Psychiatry Award; Medtronic; Neuronetics; Cyberonics; NeoSync; Eli Lilly and Company; Ortho-McNeil Janssen; Forest Research Institute; [K12 DA000357-11] FX This work was supported in part by K12 DA000357-11 (BGC) and the Leon Levy Foundation (BGC). The views and information presented do not necessarily state or reflect those of supporting organizations. We gratefully acknowledge the editorial comments of Christopher F. Koller and the clinical guidance of Patrick Ying.; Dr. Case has received support from the American Academy of Child and Adolescent Psychiatry Eli Lilly Pilot Research Award and the American Psychiatric Association Astra Zeneca Young Mindsin Psychiatry Award. In the past 3 years, Dr. Price has served as an investigator on research supported by Medtronic, Neuronetics, Cyberonics, and NeoSync, none of which involved electroconvulsive therapy. Only the research supported by NeoSync was active during the time of his involvement with this project, and he has received no direct support or compensation for any of this work. Dr. Price has served on the advisory panels of Abbott and AstraZeneca and has consulted for Abbott and AstraZeneca. Dr. Olfson has received a research grant to Columbia University from Eli Lilly and Company. Dr. Marcus has received grant support from Ortho-McNeil Janssen and Forest Research Institute and has served as a consultant to AstraZeneca. All other authors report no biomedical financial interests or potential conflicts of interest. BGC is currently affiliated with the Department of Health Services, Policy, and Practice, Public Health Program of Brown University, Providence, Rhode Island. NR 35 TC 18 Z9 18 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 15 PY 2013 VL 73 IS 2 BP 119 EP 126 DI 10.1016/j.biopsych.2012.09.005 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 053JF UT WOS:000312266800008 PM 23059049 ER PT J AU Townsend, JD Torrisi, SJ Lieberman, MD Sugar, CA Bookheimer, SY Altshuler, LL AF Townsend, Jennifer D. Torrisi, Salvatore J. Lieberman, Matthew D. Sugar, Catherine A. Bookheimer, Susan Y. Altshuler, Lori L. TI Frontal-Amygdala Connectivity Alterations During Emotion Downregulation in Bipolar I Disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Amygdala; bipolar disorder; emotion regulation; functional connectivity; functional neuroimaging; vlPFC ID MEDIAL PREFRONTAL CORTEX; FUNCTIONAL CONNECTIVITY; NEGATIVE EMOTION; VOLUNTARY SUPPRESSION; ANTERIOR CINGULATE; COGNITIVE CONTROL; AFFECTIVE STIMULI; MOOD REGULATION; RESTING STATE; DEFAULT MODE AB Background: The symptoms of bipolar disorder suggest dysfunction of emotion regulatory networks. In healthy control populations, downregulation of emotional responses activates the ventral lateral prefrontal cortex (vlPFC) and dampens amygdala activation. This study investigated frontal and limbic function and connectivity during emotion downregulation in euthymic subjects with bipolar I disorder (BPI) and healthy control subjects. Methods: Thirty BPI and 26 control subjects underwent functional magnetic resonance imaging scanning while performing an emotion processing task with passive viewing and emotion downregulation conditions. Contrasts were made for each group comparing the downregulation and passive viewing conditions, and these were entered into a between-group random effects analysis to assess group differences in activation. Psychophysiological interaction analyses were conducted to test for significant group differences in functional connectivity between the amygdala and inhibitory frontal regions (i.e., vlPFC). Results: Control subjects showed the expected robust bilateral activation of frontal and limbic regions during passive viewing and emotion downregulation tasks. Between-group analyses revealed similar activation of BPI and control subjects during passive viewing but significantly decreased activation in bilateral vlPFC, bilateral anterior and posterior cingulate, medial frontal gyrus, and bilateral dorsal lateral prefrontal cortex during emotion downregulation in subjects with BPI. Connectivity analysis demonstrated that control subjects had significantly greater negative functional connectivity between the left amygdala and bilateral vlPFC compared with subjects with BPI. Conclusions: This study provides evidence that dysfunction in the neural networks responsible for emotion regulation, including the prefrontal cortex, cingulate, and subcortical structures, are present in BPI subjects, even while euthymic. C1 [Altshuler, Lori L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Lieberman, Matthew D.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Psychol, Los Angeles, CA 90095 USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Sch Publ Hlth, Jane & Terry Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90095 USA. [Altshuler, Lori L.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. RP Altshuler, LL (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Semel Inst Neurosci & Human Behav, 300 UCLA Med Plaza,Suite 1544,Box 957057, Los Angeles, CA 90095 USA. EM laltshuler@mednet.ucla.edu FU Furlotti Family Foundation; Swift Family Foundation; National Institutes of Health; National Institute of Mental Health [R01 MH084955, K24 MH001848, R21 MH075944]; National Center for Research Resources [RR012169, RR013642, RR00865]; Abbott Laboratories FX For financial support of this study, we gratefully acknowledge the Furlotti Family Foundation, the Swift Family Foundation, and the following two components of the National Institutes of Health: the National Institute of Mental Health (R01 MH084955 [LLA], K24 MH001848 [LLA], R21 MH075944 [LLA]) and the National Center for Research Resources (RR012169, RR013642, and RR00865). Contents of this report are solely the responsibility of the authors and do not necessarily represent the official views of any sponsoring organization. For generous support, we also thank the Brain Mapping Medical Research Organization, Brain Mapping Support Foundation, Pierson-Lovelace Foundation, The Ahmanson Foundation, William M. and Linda R. Dietel Philanthropic Fund at the Northern Piedmont Community Foundation, Tamkin Foundation, Jennifer Jones-Simon Foundation, Capital Group Companies Charitable Foundation, Robson Family, and Northstar Fund. The sponsors 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.; Dr. Altshuler, Dr. Bookheimer, Dr. Lieberman, Mr. Torrisi, Dr. Sugar, and Ms. Townsend had full access to all study data and take responsibility for its integrity and the accuracy of data analysis. Dr. Altshuler has received past (and potential future) funding from Abbott Laboratories (research support and consulting honoraria); Forest Laboratories (consulting and speakers bureau honoraria); Glaxo-SmithKline (speakers bureau honoraria); and no past, but potential future honoraria from Astra-Zeneca (speakers bureau) and Merck and Co. (consulting). Ms. Townsend, Mr. Torrisi, Dr. Lieberman, Dr. Sugar, and Dr. Bookheimer report no biomedical financial interests or potential conflicts of interest. NR 85 TC 53 Z9 54 U1 5 U2 34 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 2013 VL 73 IS 2 BP 127 EP 135 DI 10.1016/j.biopsych.2012.06.030 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 053JF UT WOS:000312266800009 PM 22858151 ER PT J AU Takahashi, E Ohki, K Kim, DS AF Takahashi, Emi Ohki, Kenichi Kim, Dae-Shik TI Dissociation and convergence of the dorsal and ventral visual working memory streams in the human prefrontal cortex SO NEUROIMAGE LA English DT Article DE Visual streams; Prefrontal cortex; Short-term memory; Functional magnetic resonance imaging; Diffusion tractography; Functional connectivity ID WHITE-MATTER TRACTOGRAPHY; POSITRON-EMISSION-TOMOGRAPHY; TENSOR IMAGING TRACTOGRAPHY; LATERAL INTRAPARIETAL AREA; POSTERIOR PARIETAL CORTEX; SACCADE-RELATED ACTIVITY; SHORT-TERM-MEMORY; DIFFUSION-TENSOR; RHESUS-MONKEY; MACAQUE MONKEY AB Visual information is largely processed through two pathways in the primate brain: an object pathway from the primary visual cortex to the temporal cortex (ventral stream) and a spatial pathway to the parietal cortex (dorsal stream). Whether and to what extent dissociation exists in the human prefrontal cortex (PFC) has long been debated. We examined anatomical connections from functionally defined areas in the temporal and parietal cortices to the PFC, using noninvasive functional and diffusion-weighted magnetic resonance imaging. The right inferior frontal gyrus (IFG) received converging input from both streams, while the right superior frontal gyrus received input only from the dorsal stream. Interstream functional connectivity to the IFG was dynamically recruited only when both object and spatial information were processed. These results suggest that the human PFC receives dissociated and converging visual pathways, and that the right IFG region serves as an integrator of the two types of information. (C) 2012 Elsevier Inc. All rights reserved. C1 [Takahashi, Emi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. [Takahashi, Emi; Kim, Dae-Shik] Boston Univ, Sch Med, Ctr Biomed Imaging, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Ohki, Kenichi] Kyushu Univ, Grad Sch Med Sci, Dept Mol Physiol, Higashi Ku, Fukuoka 812, Japan. RP Takahashi, E (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Med,Div Newborn Med, Boston, MA 02115 USA. EM emi@nmr.mgh.harvard.edu RI Kim, Dae-Shik/C-2071-2011 FU National Institutes of Health [R01NS44825]; Human Frontiers Science Program; Uehara Memorial Foundation (Japan); Eunice Shriver Kennedy National Institute of Child Health and Development [R21HD069001]; Biomedical Technology Program of the National Center for Research Resources (NCRR), National Institutes of Health FX We thank Nichole Eusemann for editorial support. This work was supported by the National Institutes of Health (R01NS44825) (DSK); the Human Frontiers Science Program; and the Uehara Memorial Foundation (Japan). This work was also partly supported by the Eunice Shriver Kennedy National Institute of Child Health and Development (R21HD069001) (ET). This research was carried out in part at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41RR14075, a P41 Regional Resource supported by the Biomedical Technology Program of the National Center for Research Resources (NCRR), National Institutes of Health. NR 101 TC 9 Z9 9 U1 0 U2 24 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 2013 VL 65 BP 488 EP 498 DI 10.1016/j.neuroimage.2012.10.002 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 053PB UT WOS:000312283900045 PM 23063444 ER PT J AU Woodward, TS Feredoes, E Metzak, PD Takane, Y Manoach, DS AF Woodward, Todd S. Feredoes, Eva Metzak, Paul D. Takane, Yoshio Manoach, Dara S. TI Epoch-specific functional networks involved in working memory SO NEUROIMAGE LA English DT Article ID PRINCIPAL COMPONENT ANALYSIS; EVENT-RELATED FMRI; TERM-MEMORY; CORTEX; ATTENTION; BRAIN; DEACTIVATION; RECOGNITION; INFORMATION; MAINTENANCE AB Working memory (WM) is not a unitary construct. There are distinct processes involved in encoding information, maintaining it on-line, and using it to guide responses. The anatomical configurations of these processes are more accurately analyzed as functionally connected networks than collections of individual regions. In the current study we analyzed event-related functional magnetic resonance imaging (fMRI) data from a Sternberg Item Recognition Paradigm WM task using a multivariate analysis method that allowed the linking of functional networks to temporally-separated WM epochs. The length of the delay epochs was varied to optimize isolation of the hemodynamic response (HDR) for each task epoch. All extracted functional networks displayed statistically significant sensitivity to delay length. Novel information extracted from these networks that was not apparent in the univariate analysis of these data included involvement of the hippocampus in encoding/probe, and decreases in BOLD signal in the superior temporal gyrus (STG), along with default-mode regions, during encoding/delay. The bilateral hippocampal activity during encoding/delay fits with theoretical models of WM in which memoranda held across the short term are activated long-term memory representations. The BOLD signal decreases in the STG were unexpected, and may reflect repetition suppression effects invoked by internal repetition of letter stimuli. Thus, analysis methods focusing on how network dynamics relate to experimental conditions allowed extraction of novel information not apparent in univariate analyses, and are particularly recommended for WM experiments for which task epochs cannot be randomized. (C) 2012 Elsevier Inc. All rights reserved. C1 [Woodward, Todd S.; Metzak, Paul D.] BC Mental Hlth & Addict Res Inst, Vancouver, BC V5Z 4H4, Canada. [Woodward, Todd S.; Metzak, Paul D.] Univ British Columbia, Dept Psychiat, Vancouver, BC, Canada. [Feredoes, Eva] Univ Reading, Sch Psychol & Clin Language Sci, Reading, Berks, England. [Takane, Yoshio] McGill Univ, Dept Psychol, Montreal, PQ, Canada. [Manoach, Dara S.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Manoach, Dara S.] Athinoula A Marrinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Manoach, Dara S.] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Woodward, TS (reprint author), BC Mental Hlth & Addict Res Inst, Room A3-A116,Translat Res Bldg,3rd Floor,938 W 28, Vancouver, BC V5Z 4H4, Canada. EM todd.woodward@ubc.ca OI Feredoes, Eva/0000-0002-1665-1583; Woodward, Todd/0000-0001-8083-0079 FU Canadian Institutes of Health Research (CIHR); Michael Smith Foundation for Health Research (MSFHR); National Institute for Mental Health [R01 MH67720]; National Alliance for Research on Schizophrenia and Depression FX TSW is supported by career investigator awards from the Canadian Institutes of Health Research (CIHR) and the Michael Smith Foundation for Health Research (MSFHR). DSM was supported by the National Institute for Mental Health R01 MH67720 and the National Alliance for Research on Schizophrenia and Depression. The authors thank John Paiement for assistance with computer programming, and Jesse Friedman, Liang Wang and Jennifer Riley for assistance in data and manuscript preparation. NR 44 TC 14 Z9 14 U1 2 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN 15 PY 2013 VL 65 BP 529 EP 539 DI 10.1016/j.neuroimage.2012.09.070 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 053PB UT WOS:000312283900049 PM 23041527 ER PT J AU Adams, AS Uratsu, C Dyer, W Magid, D O'Connor, P Beck, A Butler, M Ho, PM Schmittdiel, JA AF Adams, Alyce S. Uratsu, Connie Dyer, Wendy Magid, David O'Connor, Patrick Beck, Arne Butler, Melissa Ho, P. Michael Schmittdiel, Julie A. TI Health System Factors and Antihypertensive Adherence in a Racially and Ethnically Diverse Cohort of New Users SO JAMA INTERNAL MEDICINE LA English DT Article ID MAIL-ORDER PHARMACY; ISOLATED SYSTOLIC HYPERTENSION; MEDICATION ADHERENCE; AFRICAN-AMERICANS; BLOOD-PRESSURE; UNITED-STATES; CARDIOVASCULAR-DISEASE; INTERVENTIONS; TRENDS; DISPARITIES AB Background: The purpose of this study was to identify potential health system solutions to suboptimal use of antihypertensive therapy in a diverse cohort of patients initiating treatment. Methods: Using a hypertension registry at Kaiser Permanente Northern California, we conducted a retrospective cohort study of 44 167 adults (age, >= 18 years) with hypertension who were new users of antihypertensive therapy in 2008. We used multivariate logistic regression analysis to model the relationships between race/ethnicity, specific health system factors, and early non-persistence (failing to refill the first prescription within 90 days) and nonadherence (<80% of days covered during the 12 months following the start of treatment), respectively, controlling for sociodemographic and clinical risk factors. Results: More than 30% of patients were early nonpersistent and 1 in 5 were nonadherent to therapy. Nonwhites were more likely to exhibit both types of suboptimal medication-taking behavior compared with whites. In logistic regression models adjusted for sociodemographic, clinical, and health system factors, nonwhite race was associated with early nonpersistence (black: odds ratio, 1.56 [95% CI, 1.43-1.70]; Asian: 1.40 [1.29-1.51]; Hispanic: 1.46 [1.35-1.57]) and nonadherence (black: 1.55 [1.37-1.77]; Asian: 1.13 [1.00-1.28]; Hispanic: 1.46 [1.31-1.63]). The likelihood of early nonpersistence varied between Asians and Hispanics by choice of first-line therapy. In addition, racial and ethnic differences in nonadherence were appreciably attenuated when medication co-payment and mail-order pharmacy use were accounted for in the models. Conclusions: Racial/ethnic differences in medication-taking behavior occur early in the course of treatment. However, health system strategies designed to reduce patient co-payments, ease access to medications, and optimize the choice of initial therapy may be effective tools in narrowing persistent gaps in the use of these and other clinically effective therapies. JAMA Intern Med. 2013;173(1):54-61. Published online December 10, 2012. doi:10.1001/2013.jamainternmed.955 C1 [Adams, Alyce S.; Uratsu, Connie; Dyer, Wendy; Schmittdiel, Julie A.] Kaiser Permanente, Div Res, Oakland, CA 94612 USA. [Magid, David; Beck, Arne; Ho, P. Michael] Kaiser Permanente, Inst Res, Denver, CO USA. [O'Connor, Patrick] HealthPartners Res Fdn, Minneapolis, MN USA. [Butler, Melissa] Kaiser Permanente, Ctr Hlth Res Southeast, Atlanta, GA USA. [Ho, P. Michael] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Adams, AS (reprint author), Kaiser Permanente, Div Res, 2000 Broadway, Oakland, CA 94612 USA. EM Alyce.S.Adams@kp.org FU National Heart, Lung, and Blood Institute [3U19HL091179-04S1]; National Institute for Mental Health; Health Delivery Systems Center for Diabetes Translational Research [P30DK092924]; National Institute for Diabetes and Digestive and Kidney Diseases FX This study was funded by 3U19HL091179-04S1 (National Heart, Lung, and Blood Institute) and the National Institute for Mental Health as a supplement to the Health Maintenance Organization Research Network Cardiovascular Disease Network. Additional support for Drs Adams, O'Connor, and Schmittdiel was provided by P30DK092924 (Health Delivery Systems Center for Diabetes Translational Research), funded by the National Institute for Diabetes and Digestive and Kidney Diseases. NR 44 TC 15 Z9 15 U1 2 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JAN 14 PY 2013 VL 173 IS 1 BP 54 EP 61 DI 10.1001/2013.jamainternmed.955 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 121JF UT WOS:000317238800013 PM 23229831 ER PT J AU Trautner, BW AF Trautner, Barbara W. TI New Perspectives on Urinary Tract Infection in Men SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID CLINICAL-PRACTICE GUIDELINES; ASYMPTOMATIC BACTERIURIA; DISEASES-SOCIETY; AMERICA; DIAGNOSIS; ADULTS; WOMEN C1 Baylor Coll Med, Infect Dis Sect, Hlth Serv Res Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Trautner, BW (reprint author), Baylor Coll Med, Infect Dis Sect, Hlth Serv Res Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM trautner@bcm.edu NR 9 TC 1 Z9 1 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JAN 14 PY 2013 VL 173 IS 1 BP 68 EP 70 DI 10.1001/jamainternmed.2013.1783 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 121JF UT WOS:000317238800015 PM 23212451 ER PT J AU Bao, YR Johansen, KL AF Bao, Yeran Johansen, Kirsten L. TI Frailty in Dialysis-Dependent Patients With End-Stage Renal Disease Reply SO JAMA INTERNAL MEDICINE LA English DT Letter ID WOMENS HEALTH; PHENOTYPE; OLDER C1 [Bao, Yeran] Univ Calif San Francisco, Div Endocrinol, San Francisco, CA 94143 USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Johansen, Kirsten L.] San Francisco VA Med Ctr, USRDS Nutr Special Studies Ctr, San Francisco, CA USA. [Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA USA. [Johansen, Kirsten L.] USRDS Rehabil Qual Life Special Studies Ctr, Atlanta, GA USA. RP Bao, YR (reprint author), Univ Calif San Francisco, Div Endocrinol, 400 Parnassus Ave,Ste A550,Box 1222, San Francisco, CA 94143 USA. EM yeranbao@gmail.com NR 5 TC 0 Z9 0 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JAN 14 PY 2013 VL 173 IS 1 BP 79 EP 79 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 121JF UT WOS:000317238800022 PM 23318592 ER PT J AU Zhang, EZ Oh, WY Villiger, ML Chen, L Bouma, BE Vakoc, BJ AF Zhang, Ellen Ziyi Oh, Wang-Yuhl Villiger, Martin L. Chen, Liang Bouma, Brett E. Vakoc, Benjamin J. TI Numerical compensation of system polarization mode dispersion in polarization-sensitive optical coherence tomography SO OPTICS EXPRESS LA English DT Article ID BIOLOGICAL TISSUE; LIGHT; MODULATION AB Polarization mode dispersion (PMD), which can be induced by circulators or even moderate lengths of optical fiber, is known to be a dominant source of instrumentation noise in fiber-based PS-OCT systems. In this paper we propose a novel PMD compensation method that measures system PMD using three fixed calibration signals, numerically corrects for these instrument effects and reconstructs an improved sample image. Using a frequency multiplexed PS-OFDI setup, we validate the proposed method by comparing birefringence noise in images of intralipid, muscle, and tendon with and without PMD compensation. (C) 2013 Optical Society of America C1 [Zhang, Ellen Ziyi; Villiger, Martin L.; Bouma, Brett E.; Vakoc, Benjamin J.] Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. [Zhang, Ellen Ziyi; Villiger, Martin L.; Bouma, Brett E.; Vakoc, Benjamin J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Oh, Wang-Yuhl] Korea Adv Inst Sci & Technol, Dept Mech Engn, Taejon 305701, South Korea. [Chen, Liang] Univ Ottawa, Dept Phys, Ottawa, ON K1N 6N5, Canada. [Bouma, Brett E.; Vakoc, Benjamin J.] Harvard Massachusetts Inst Technol Div Hlth Sci &, Cambridge, MA 02142 USA. RP Zhang, EZ (reprint author), Harvard Univ, Sch Med, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM zzhang0@partners.org FU Center for Biomedical OCT Research and Translation [P41EB015903]; National Center for Research Resources; National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health; NIH [R01CA163528]; National Research Foundation of Korea (NRF) [2012-0005633] FX We would like to thank Dr. Wei Xu at Harvard Medical School for valuable discussion on analytic derivation part of this work. This project was supported by the Center for Biomedical OCT Research and Translation through Grant Number P41EB015903, awarded by the National Center for Research Resources and the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health. This work was supported by NIH grant R01CA163528. This work was also supported by the National Research Foundation of Korea (NRF) grant 2012-0005633. NR 26 TC 20 Z9 20 U1 1 U2 13 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 14 PY 2013 VL 21 IS 1 BP 1163 EP 1180 DI 10.1364/OE.21.001163 PG 18 WC Optics SC Optics GA 104JF UT WOS:000315988100140 PM 23389009 ER PT J AU Giancarlo, R Lo Bosco, G Pinello, L Utro, F AF Giancarlo, Raffaele Lo Bosco, Giosue Pinello, Luca Utro, Filippo TI A methodology to assess the intrinsic discriminative ability of a distance function and its interplay with clustering algorithms for microarray data analysis SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 7th International Meeting on Computational Intelligence Methods for Bioinformatics and Biostatistics (CIBB 2010) CY SEP 16-18, 2010 CL Palermo, ITALY SP Provincia Regionale Palermo, CNR, Dept Informat & Commun Technol, CNR, Ist Calcolo & Reti Alte Prestazioni, E4 Comp Engn, Informat Commerciale, MISCO ID GENE-EXPRESSION DATA; CLASS DISCOVERY; VALIDATION AB Background: Clustering is one of the most well known activities in scientific investigation and the object of research in many disciplines, ranging from statistics to computer science. Following Handl et al., it can be summarized as a three step process: (1) choice of a distance function; (2) choice of a clustering algorithm; (3) choice of a validation method. Although such a purist approach to clustering is hardly seen in many areas of science, genomic data require that level of attention, if inferences made from cluster analysis have to be of some relevance to biomedical research. Results: A procedure is proposed for the assessment of the discriminative ability of a distance function. That is, the evaluation of the ability of a distance function to capture structure in a dataset. It is based on the introduction of a new external validation index, referred to as Balanced Misclassification Index (BMI, for short) and of a nontrivial modification of the well known Receiver Operating Curve (ROC, for short), which we refer to as Corrected ROC (CROC, for short). The main results are: (a) a quantitative and qualitative method to describe the intrinsic separation ability of a distance; (b) a quantitative method to assess the performance of a clustering algorithm in conjunction with the intrinsic separation ability of a distance function. The proposed procedure is more informative than the ones available in the literature due to the adopted tools. Indeed, the first one allows to map distances and clustering solutions as graphical objects on a plane, and gives information about the bias of the clustering algorithm with respect to a distance. The second tool is a new external validity index which shows similar performances with respect to the state of the art, but with more flexibility, allowing for a broader spectrum of applications. In fact, it allows not only to quantify the merit of each clustering solution but also to quantify the agglomerative or divisive errors due to the algorithm. Conclusions: The new methodology has been used to experimentally study three popular distance functions, namely, Euclidean distance d(2), Pearson correlation d(r) and mutual information d(MI). Based on the results of the experiments, we have that the Euclidean and Pearson correlation distances have a good intrinsic discrimination ability. Conversely, the mutual information distance does not seem to offer the same flexibility and versatility as the other two distances. Apparently, that is due to well known problems in its estimation. since it requires that a dataset must have a substantial number of features to be reliable. Nevertheless, taking into account such a fact, together with results presented in Priness et al., one receives an indication that d(MI) may be superior to the other distances considered in this study only in conjunction with clustering algorithms specifically designed for its use. In addition, it results that K-means, Average Link, and Complete link clustering algorithms are in most cases able to improve the discriminative ability of the distances considered in this study with respect to clustering. The methodology has a range of applicability that goes well beyond microarray data since it is independent of the nature of the input data. The only requirement is that the input data must have the same format of a "feature matrix". In particular it can be used to cluster ChIP-seq data. C1 [Giancarlo, Raffaele; Lo Bosco, Giosue] Univ Palermo, Dipartimento Matemat & Informat, I-90123 Palermo, Italy. [Pinello, Luca] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Pinello, Luca] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Utro, Filippo] IBM TJ Watson Res Ctr, Computat Genom Grp, Yorktown Hts, NY 10598 USA. RP Lo Bosco, G (reprint author), Univ Palermo, Dipartimento Matemat & Informat, Via Archirafi 34, I-90123 Palermo, Italy. EM giosue.lobosco@unipa.it RI Lo Bosco, Giosue/C-7644-2011 OI Lo Bosco, Giosue/0000-0002-1602-0693 NR 31 TC 3 Z9 3 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JAN 14 PY 2013 VL 14 SU 1 AR S6 DI 10.1186/1471-2105-14-S1-S6 PG 14 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 083MD UT WOS:000314467500007 PM 23369037 ER PT J AU Cantrell, J Vallone, DM Thrasher, JF Nagler, RH Feirman, SP Muenz, LR He, DY Viswanath, K AF Cantrell, Jennifer Vallone, Donna M. Thrasher, James F. Nagler, Rebekah H. Feirman, Shari P. Muenz, Larry R. He, David Y. Viswanath, Kasisomayajula TI Impact of Tobacco-Related Health Warning Labels across Socioeconomic, Race and Ethnic Groups: Results from a Randomized Web-Based Experiment SO PLOS ONE LA English DT Article ID 4 COUNTRY SURVEY; ITC 4-COUNTRY SURVEY; PICTORIAL WARNINGS; CIGARETTE PACKAGES; SMOKING-CESSATION; QUITTING FINDINGS; MEDIA CAMPAIGNS; UNITED-STATES; DISPARITIES; SMOKERS AB Background: The U. S. Family Smoking Prevention and Tobacco Control Act of 2009 requires updating of the existing text-only health warning labels on tobacco packaging with nine new warning statements accompanied by pictorial images. Survey and experimental research in the U. S. and other countries supports the effectiveness of pictorial health warning labels compared with text-only warnings for informing smokers about the risks of smoking and encouraging cessation. Yet very little research has examined differences in reactions to warning labels by race/ethnicity, education or income despite evidence that population subgroups may differ in their ability to process health information. The purpose of the present study was to evaluate the potential impact of pictorial warning labels compared with text-only labels among U. S. adult smokers from diverse racial/ethnic and socioeconomic subgroups. Methods/Findings: Participants were adult smokers recruited from two online research panels (n = 3,371) into a web-based experimental study to view either the new pictorial warnings or text-only warnings. Participants viewed the labels and reported their reactions. Adjusted regression models demonstrated significantly stronger reactions for the pictorial condition for each outcome salience (b = 0.62, p < .001); perceived impact (b = 0.44, p < .001); credibility (OR = 1.41, 95% CI = 1.22-1.62), and intention to quit (OR = 1.30, 95% CI = 1.10-1.53). No significant results were found for interactions between condition and race/ethnicity, education, or income. The only exception concerned the intention to quit outcome, where the condition-by-education interaction was nearly significant (p = 0.057). Conclusions: Findings suggest that the greater impact of the pictorial warning label compared to the text-only warning is consistent across diverse racial/ethnic and socioeconomic populations. Given their great reach, pictorial health warning labels may be one of the few tobacco control policies that have the potential to reduce communication inequalities across groups. Policies that establish strong pictorial warning labels on tobacco packaging may be instrumental in reducing the toll of the tobacco epidemic, particularly within vulnerable communities. C1 [Cantrell, Jennifer; Vallone, Donna M.; Feirman, Shari P.] Legacy Fdn, Dept Res & Evaluat, Washington, DC USA. [Thrasher, James F.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Hlth Promot Educ & Behav, Columbia, SC 29208 USA. [Nagler, Rebekah H.; Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Ctr Community Based Res, Dept Soc Human Dev & Hlth,Dana Farber Canc Inst, Boston, MA 02115 USA. [Muenz, Larry R.; He, David Y.] Larry R Muenz & Associates, Gaithersburg, MD USA. RP Cantrell, J (reprint author), Legacy Fdn, Dept Res & Evaluat, Washington, DC USA. EM jcantrell@legacyforhealth.org FU Legacy; Legacy Foundation FX This study was supported by internal funding at Legacy. Legacy Foundation funded the study. Research and Evaluation Department staff within Legacy Foundation along with external collaborators listed as co-authors designed and conducted the study, organized data collection, conducted analysis and wrote the manuscript. NR 77 TC 28 Z9 28 U1 5 U2 24 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 2013 VL 8 IS 1 AR e52206 DI 10.1371/journal.pone.0052206 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 087KE UT WOS:000314759400012 PM 23341895 ER PT J AU Rada, B Jendrysik, MA Pang, L Hayes, CP Yoo, DG Park, JJ Moskowitz, SM Malech, HL Leto, TL AF Rada, Balazs Jendrysik, Meghan A. Pang, Lan Hayes, Craig P. Yoo, Dae-goon Park, Jonathan J. Moskowitz, Samuel M. Malech, Harry L. Leto, Thomas L. TI Pyocyanin-Enhanced Neutrophil Extracellular Trap Formation Requires the NADPH Oxidase SO PLOS ONE LA English DT Article ID AIRWAY EPITHELIAL-CELLS; PSEUDOMONAS-AERUGINOSA; CYSTIC-FIBROSIS; DUAL OXIDASE; INFECTION; SPUTUM; ACTIVATION; MECHANISM; AUTOPHAGY; PATHWAY AB Beyond intracellular killing, a novel neutrophil-based antimicrobial mechanism has been recently discovered: entrapment and killing by neutrophil extracellular traps (NETs). NETs consist of extruded nuclear DNA webs decorated with granule proteins. Although NET formation is an important innate immune mechanism, uncontrolled NET release damages host tissues and has been linked to several diseases including cystic fibrosis (CF). The major CF airway pathogen Pseudomonas aeruginosa establishes chronic infection. Pseudomonas imbedded within biofilms is protected against the immune system, but maintains chronic inflammation that worsens disease symptoms. Aberrant NET release from recruited neutrophils was found in CF, but the underlying mechanisms remain unclear. One of the most important Pseudomonas virulence factors is pyocyanin, a redox-active pigment that has been associated with diminished lung function in CF. Here we show that pyocyanin promotes NET formation in a time-and dose-dependent manner. Most CF Pseudomonas clinical isolates tested produce pyocyanin in vitro. Pyocyanin-derived reactive oxygen species are required for its NET release. Inhibitor experiments demonstrated involvement of Jun N-terminal Kinase (JNK) and phosphatidylinositol 3-Kinase (PI3K) in pyocyanin-induced NET formation. Pyocyanin-induced NETs also require the NADPH oxidase because NET release in chronic granulomatous disease neutrophils was greatly reduced. Comparison of neutrophils from gp91phox- and p47phox-deficient patients revealed that pyocyanin-triggered NET formation is proportional to their residual superoxide production. Our studies identify pyocyanin as the first secreted bacterial toxin that enhances NET formation. The involvement of NADPH oxidase in pyocyanin-induced NET formation represents a novel mechanism of pyocyanin toxicity. C1 [Rada, Balazs; Jendrysik, Meghan A.; Park, Jonathan J.; Malech, Harry L.; Leto, Thomas L.] NIAID, Lab Host Def, NIH, Rockville, MD USA. [Rada, Balazs; Pang, Lan; Hayes, Craig P.; Yoo, Dae-goon] Univ Georgia, Coll Vet Med, Dept Infect Dis, Athens, GA USA. [Moskowitz, Samuel M.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Moskowitz, Samuel M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Rada, B (reprint author), NIAID, Lab Host Def, NIH, Rockville, MD USA. EM radab@uga.edu; tleto@niaid.nih.gov OI Malech, Harry/0000-0001-5874-5775 FU National Institutes of Health, National Institute of Allergy and Infectious Diseases [ZO1-AI-000614]; Public Health Service from the National Heart Lung and Blood Institute [K08HL067903]; Public Health Service from the National Institute of Allergy and Infectious Diseases [R01AI067653]; CF Foundation [MOSKOW01A0] FX This work was supported by funds to TLL from the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases (ZO1-AI-000614), by Public Health Service grants K08HL067903 to SMM from the National Heart Lung and Blood Institute and R01AI067653 to SMM from the National Institute of Allergy and Infectious Diseases and by grant MOSKOW01A0 to SMM from the CF Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 30 Z9 32 U1 0 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 14 PY 2013 VL 8 IS 1 AR e54205 DI 10.1371/journal.pone.0054205 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 087KE UT WOS:000314759400133 PM 23342104 ER PT J AU Corcoran, RB Cheng, KA Hata, AN Faber, AC Ebi, H Coffee, EM Greninger, P Brown, RD Godfrey, JT Cohoon, TJ Song, YC Lifshits, E Hung, KE Shioda, T Dias-Santagata, D Singh, A Settleman, J Benes, CH Mino-Kenudson, M Wong, KK Engelman, JA AF Corcoran, Ryan B. Cheng, Katherine A. Hata, Aaron N. Faber, Anthony C. Ebi, Hiromichi Coffee, Erin M. Greninger, Patricia Brown, Ronald D. Godfrey, Jason T. Cohoon, Travis J. Song, Youngchul Lifshits, Eugene Hung, Kenneth E. Shioda, Toshi Dias-Santagata, Dora Singh, Anurag Settleman, Jeffrey Benes, Cyril H. Mino-Kenudson, Mari Wong, Kwok-Kin Engelman, Jeffrey A. TI Synthetic Lethal Interaction of Combined BCL-XL and MEK Inhibition Promotes Tumor Regressions in KRAS Mutant Cancer Models SO CANCER CELL LA English DT Article ID GENE-EXPRESSION SIGNATURE; RAS ONCOGENE; K-RAS; APOPTOSIS; CELLS; SENSITIVITY; ACTIVATION; RESISTANCE; INDUCTION; PATHWAYS AB KRAS is the most commonly mutated oncogene, yet no effective targeted therapies exist for KRAS mutant cancers. We developed a pooled shRNA-drug screen strategy to identify genes that, when inhibited, cooperate with MEK inhibitors to effectively treat KRAS mutant cancer cells. The anti-apoptotic BH3 family gene BCL-XL emerged as a top hit through this approach. ABT-263 (navitoclax), a chemical inhibitor that blocks the ability of BCL-XL to bind and inhibit pro-apoptotic proteins, in combination with a MEK inhibitor led to dramatic apoptosis in many KRAS mutant cell lines from different tissue types. This combination caused marked in vivo tumor regressions in KRAS mutant xenografts and in a genetically engineered KRAS-driven lung cancer mouse model, supporting combined BCL-XL/MEK inhibition as a potential therapeutic approach for KRAS mutant cancers. C1 [Corcoran, Ryan B.; Hata, Aaron N.; Faber, Anthony C.; Ebi, Hiromichi; Coffee, Erin M.; Greninger, Patricia; Brown, Ronald D.; Godfrey, Jason T.; Song, Youngchul; Lifshits, Eugene; Shioda, Toshi; Benes, Cyril H.; Engelman, Jeffrey A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. [Corcoran, Ryan B.; Hata, Aaron N.; Faber, Anthony C.; Ebi, Hiromichi; Engelman, Jeffrey A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Cheng, Katherine A.; Cohoon, Travis J.; Wong, Kwok-Kin] Dana Farber Canc Inst, Boston, MA 02114 USA. [Coffee, Erin M.; Hung, Kenneth E.] Tufts Med Ctr, Div Gastroenterol, Boston, MA 02111 USA. [Dias-Santagata, Dora; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. [Singh, Anurag] Boston Univ, Boston, MA 02118 USA. [Settleman, Jeffrey] Genentech Inc, San Francisco, CA 94080 USA. RP Engelman, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. EM jengelman@partners.org RI Singh, Anurag/C-7347-2014; OI Singh, Anurag/0000-0003-4705-8683; Ebi, Hiromichi/0000-0003-3155-7576; wong, kwok kin/0000-0001-6323-235X FU NIH [P50 CA127003, P50CA090578, R01CA140594, 1U54HG006097-01, R01CA122794, R01CA163896]; American Cancer Society Institutional Research grant; Damon Runyon Clinical Investigator award; Conquer Cancer Foundation of ASCO Young Investigator award; V Foundation [K08CA120060, R01CA137008, 1U01CA41457-01]; American Cancer Society [RSG-06-102-01-CCE]; Ellison Foundation Scholar; AstraZeneca FX This study was supported by grants from the NIH Gastrointestinal SPORE P50 CA127003 (to R.C. and J.E.); an American Cancer Society Institutional Research grant, a Damon Runyon Clinical Investigator award, a Conquer Cancer Foundation of ASCO Young Investigator award (to R.C.); and K08CA120060, R01CA137008, 1U01CA41457-01, the V Foundation, American Cancer Society RSG-06-102-01-CCE, the Ellison Foundation Scholar (all to J.E.); NIH Lung SPORE P50CA090578, R01CA140594 (to J.E. and K.W.); R01CA122794 and R01CA163896 (to K.W.); and 1U54HG006097-01 (to C.B.). Research support for this study was also provided to J.E. by AstraZeneca. NR 28 TC 126 Z9 127 U1 2 U2 28 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JAN 14 PY 2013 VL 23 IS 1 BP 121 EP 128 DI 10.1016/j.ccr.2012.11.007 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 073RB UT WOS:000313759100012 PM 23245996 ER PT J AU Li, ZZ Gilbert, JA Zhang, Y Zhang, M Qiu, Q Ramanujan, K Shavlakadze, T Eash, JK Scaramozza, A Goddeeris, MM Kirsch, DG Campbell, KP Brack, AS Glass, DJ AF Li, Zhizhong Gilbert, Jason A. Zhang, Yunyu Zhang, Minsi Qiu, Qiong Ramanujan, Krishnan Shavlakadze, Tea Eash, John K. Scaramozza, Annarita Goddeeris, Matthew M. Kirsch, David G. Campbell, Kevin P. Brack, Andrew S. Glass, David J. TI An HMGA2-IGF2BP2 Axis Regulates Myoblast Proliferation and Myogenesis (vol 23, pg 1176, 2012) SO DEVELOPMENTAL CELL LA English DT Correction C1 [Li, Zhizhong; Gilbert, Jason A.; Zhang, Yunyu; Ramanujan, Krishnan; Shavlakadze, Tea; Eash, John K.; Glass, David J.] Novartis Inst Biomed Res, Cambridge, MA 02139 USA. [Zhang, Minsi; Kirsch, David G.] Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. [Qiu, Qiong; Kirsch, David G.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC 27710 USA. [Scaramozza, Annarita; Brack, Andrew S.] Harvard Univ, Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Scaramozza, Annarita; Brack, Andrew S.] Harvard Univ, Harvard Stem Cell Inst, Boston, MA 02114 USA. [Goddeeris, Matthew M.; Campbell, Kevin P.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Internal Med, Iowa City, IA 52242 USA. [Goddeeris, Matthew M.; Campbell, Kevin P.] Howard Hughes Med Inst, Senator Paul D Wellstone Muscular Dystrophy Cooper, Dept Mol Physiol & Biophys, Dept Neurol, Chevy Chase, MD USA. RP Glass, DJ (reprint author), Novartis Inst Biomed Res, Cambridge, MA 02139 USA. EM david.glass@novartis.com NR 1 TC 0 Z9 0 U1 1 U2 1 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 14 PY 2013 VL 24 IS 1 BP 112 EP 112 DI 10.1016/j.devcel.2012.12.007 PG 1 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 108OL UT WOS:000316305200010 ER PT J AU Buckle, T Kuil, J van den Berg, NS Bunschoten, A Lamb, HJ Yuan, HH Josephson, L Jonkers, J Borowsky, AD van Leeuwen, FWB AF Buckle, Tessa Kuil, Joeri van den Berg, Nynke S. Bunschoten, Anton Lamb, Hildo J. Yuan, Hushan Josephson, Lee Jonkers, Jos Borowsky, Alexander D. van Leeuwen, Fijs W. B. TI Use of a Single Hybrid Imaging Agent for Integration of Target Validation with In Vivo and Ex Vivo Imaging of Mouse Tumor Lesions Resembling Human DCIS SO PLOS ONE LA English DT Article ID CHEMOKINE RECEPTOR CXCR4; BREAST-CANCER; FLOW-CYTOMETRY; PROSTATE-CANCER; EXPRESSION; CARCINOMA; PEPTIDE; GROWTH; MODEL; OVEREXPRESSION AB Screening of biomarker expression levels in tumor biopsy samples not only provides an assessment of prognostic and predictive factors, but may also be used for selection of biomarker-specific imaging strategies. To assess the feasibility of using a biopsy specimen for a personalized selection of an imaging agent, the chemokine receptor 4 (CXCR4) was used as a reference biomarker. Methods: A hybrid CXCR4 targeting peptide (MSAP-Ac-TZ14011) containing a fluorescent dye and a chelate for radioactive labeling was used to directly compare initial flow cytometry-based target validation in fresh tumor tissue to in vivo single photon emission computed tomography (SPECT) imaging and in vivo and ex vivo fluorescence imaging. Results: Flow cytometric analysis of mouse tumor derived cell suspensions enabled discrimination between 4T1 control tumor lesions (with low levels of CXCR4 expression) and CXCR4 positive early, intermediate and late stage MIN-O lesions based on their CXCR4 expression levels; CXCR4(basal), CXCR4(+) and CXCR4(++) cell populations could be accurately discriminated. Mean fluorescent intensity ratios between expression in MIN-O and 4T1 tissue found with flow cytometry were comparable to ratios obtained with in vivo SPECT/CT and fluorescence imaging, ex vivo fluorescence evaluation and standard immunohistochemistry. Conclusion: The hybrid nature of a targeting imaging agent like MSAP-Ac-TZ14011 enables integration of target selection, in vivo imaging and ex vivo validation using a single agent. The use of biopsy tissue for biomarker screening can readily be expanded to other targeting hybrid imaging agents and can possibly help increase the clinical applicability of tumor-specific imaging approaches. C1 [Buckle, Tessa; Kuil, Joeri; van den Berg, Nynke S.; Bunschoten, Anton; van Leeuwen, Fijs W. B.] Leiden Univ, Med Ctr, Dept Radiol, Intervent Mol Imaging Lab, Leiden, Netherlands. [Buckle, Tessa; Kuil, Joeri; van den Berg, Nynke S.; Bunschoten, Anton; van Leeuwen, Fijs W. B.] Netherlands Canc Inst Antoni van Leeuwenhoekhuis, Dept Radiol, Amsterdam, Netherlands. [Buckle, Tessa; Kuil, Joeri; van den Berg, Nynke S.; Bunschoten, Anton; van Leeuwen, Fijs W. B.] Netherlands Canc Inst Antoni van Leeuwenhoekhuis, Dept Nucl Med, Amsterdam, Netherlands. [Lamb, Hildo J.] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands. [Yuan, Hushan; Josephson, Lee] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. [Yuan, Hushan; Josephson, Lee] Harvard Univ, Sch Med, Charlestown, MA USA. [Jonkers, Jos] Netherlands Canc Inst Antoni van Leeuwenhoek Hosp, Div Cell Biol, Amsterdam, Netherlands. [Borowsky, Alexander D.] Univ Calif Davis, Sch Med, Ctr Comparat Med, Dept Pathol & Lab Med, Sacramento, CA 95817 USA. RP van Leeuwen, FWB (reprint author), Leiden Univ, Med Ctr, Dept Radiol, Intervent Mol Imaging Lab, Leiden, Netherlands. EM F.W.B.van_Leeuwen@lumc.nl OI van leeuwen, Fijs/0000-0002-6844-4025; Buckle, Tessa/0000-0003-2980-6895 FU Dutch Cancer Society [PGF 2009-4344]; VIDI grant [STW11272]; FP7-HYPERImage [201651]; Centre for Translational Molecular Medicine grant, project Breast CARE [030-104]; National Center for Research resources grant [K26 RR0243037]; National Institutes of Health [R01 EB-009691, EB011996] FX Funding: This research is supported by a Dutch Cancer Society translational research award (Grant No. PGF 2009-4344; FvL), a VIDI grant (Grant No. STW11272, FvL) and via FP7-HYPERImage (Grant No. 201651; TB), a Centre for Translational Molecular Medicine grant, project Breast CARE (Grant No. 030-104; JK) a National Center for Research resources grant (K26 RR0243037; ADB), and by National Institutes of Health grants R01 EB-009691 and EB011996 (LJ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 40 TC 7 Z9 7 U1 1 U2 18 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 2013 VL 8 IS 1 AR e48324 DI 10.1371/journal.pone.0048324 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 086RY UT WOS:000314705800005 PM 23326303 ER PT J AU Lu, N Chen, Y Wang, ZM Chen, GL Lin, Q Chen, ZY Li, HW AF Lu, Na Chen, Yan Wang, Zhengmin Chen, Guoling Lin, Qin Chen, Zheng-Yi Li, Huawei TI Sonic hedgehog initiates cochlear hair cell regeneration through downregulation of retinoblastoma protein SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Retinoblastoma 1; Hedgehog; Inner ear; Cochlea; Hair cell; Regeneration ID INNER-EAR DEVELOPMENT; SUPPORTING CELLS; IN-VITRO; DIFFERENTIATION; PROLIFERATION; PROGENITORS; PRB; MEDULLOBLASTOMA; SPECIFICATION; PROMOTES AB Cell cycle re-entry by cochlear supporting cells and/or hair cells is considered one of the best approaches for restoring hearing loss as a result of hair cell damage. To identify mechanisms that can be modulated to initiate cell cycle re-entry and hair cell regeneration, we studied the effect of activating the sonic hedgehog (Shh) pathway. We show that Shh signaling in postnatal rat cochleae damaged by neomycin leads to renewed proliferation of supporting cells and hair cells. Further, proliferating supporting cells are likely to transdifferentiate into hair cells. Shh treatment leads to inhibition of retinoblastoma protein (pRb) by increasing phosphorylated pRb and reducing retinoblastoma gene transcription. This results in upregulation of cyclins B1, D2, and D3, and CDK1. These results suggest that Shh signaling induces cell cycle re-entry in cochlear sensory epithelium and the production of new hair cells, in part by attenuating pRb function. This study provides an additional route to modulate pRb function with important implications in mammalian hair cell regeneration. (C) 2012 Elsevier Inc. All rights reserved. C1 [Lu, Na; Wang, Zhengmin; Chen, Guoling; Lin, Qin; Chen, Zheng-Yi; Li, Huawei] Fudan Univ, Otol Skull Base Surg Dept, Inst Hearing Res, Eye & ENT Hosp,Shanghai Med Sch, Shanghai 200031, Peoples R China. [Lu, Na; Chen, Zheng-Yi] Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. [Lu, Na; Chen, Zheng-Yi] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. [Lu, Na; Chen, Zheng-Yi] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Chen, Yan] Fudan Univ, Cent Lab, Inst Hearing Res, Eye & ENT Hosp,Shanghai Med Sch, Shanghai 200031, Peoples R China. [Wang, Zhengmin; Li, Huawei] Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China. [Lin, Qin] Fujian Med Univ, Affiliated Hosp 1, Dept Otolaryngol, Otolaryngol Inst Fujian Prov, Fuzhou, Peoples R China. RP Chen, ZY (reprint author), Fudan Univ, Otol Skull Base Surg Dept, Inst Hearing Res, Eye & ENT Hosp,Shanghai Med Sch, Shanghai 200031, Peoples R China. EM Zheng-yi_chen@meei.harvard.edu; hwli@shmu.edu.cn FU Major State Basic Research Development Program of China (973 Program) [2011CB504506, 2010CB945503]; National Natural Science Foundation of China [81070793, 81001544, 30672300]; Shanghai Nature Science Found [11ZR1406000]; National Institutes of Health [R01 DC006908] FX This work was supported by grants from the Major State Basic Research Development Program of China (973 Program) (2011CB504506 and 2010CB945503), the National Natural Science Foundation of China (No. 81070793, 81001544, 30672300), the Shanghai Nature Science Found (11ZR1406000), and the National Institutes of Health (R01 DC006908). The authors have no conflict of interests to declare. NR 25 TC 6 Z9 6 U1 0 U2 22 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 11 PY 2013 VL 430 IS 2 BP 700 EP 705 DI 10.1016/j.bbrc.2012.11.088 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 080QH UT WOS:000314257800044 PM 23211596 ER PT J AU Swirski, FK Nahrendorf, M AF Swirski, Filip K. Nahrendorf, Matthias TI Leukocyte Behavior in Atherosclerosis, Myocardial Infarction, and Heart Failure SO SCIENCE LA English DT Review ID STEM-CELL PROLIFERATION; DENDRITIC CELLS; HEMATOPOIETIC STEM; MONOCYTE SUBSETS; INFLAMMATORY RESPONSES; PROGENITOR CELLS; APOLIPOPROTEIN-E; PROTECTIVE ROLE; DEFICIENT MICE; T-LYMPHOCYTES AB Cardiovascular diseases claim more lives worldwide than any other. Etiologically, the dominant trajectory involves atherosclerosis, a chronic inflammatory process of lipid-rich lesion growth in the vascular wall that can cause life-threatening myocardial infarction (MI). Those who survive MI can develop congestive heart failure, a chronic condition of inadequate pump activity that is frequently fatal. Leukocytes (white blood cells) are important participants at the various stages of cardiovascular disease progression and complication. This Review will discuss leukocyte function in atherosclerosis, MI, and heart failure. C1 [Swirski, Filip K.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Swirski, FK (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM fswirski@mgh.harvard.edu; mnahrendorf@mgh.harvard.edu FU National Heart, Lung, and Blood Institute [R01HL095612, R01HL095629, R01HL096576] FX We gratefully acknowledge R. Weissleder and P. Libby for fruitful discussion and critical reading of the manuscript. This work was supported in part by National Heart, Lung, and Blood Institute grants R01HL095612, R01HL095629, and R01HL096576. NR 60 TC 232 Z9 244 U1 10 U2 120 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JAN 11 PY 2013 VL 339 IS 6116 BP 161 EP 166 DI 10.1126/science.1230719 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 067XI UT WOS:000313328200034 PM 23307733 ER PT J AU Shyh-Chang, N Locasale, JW Lyssiotis, CA Zheng, YX Teo, RY Ratanasirintrawoot, S Zhang, J Onder, T Unternaehrer, JJ Zhu, H Asara, JM Daley, GQ Cantley, LC AF Ng Shyh-Chang Locasale, Jason W. Lyssiotis, Costas A. Zheng, Yuxiang Teo, Ren Yi Ratanasirintrawoot, Sutheera Zhang, Jin Onder, Tamer Unternaehrer, Juli J. Zhu, Hao Asara, John M. Daley, George Q. Cantley, Lewis C. TI Influence of Threonine Metabolism on S-Adenosylmethionine and Histone Methylation SO SCIENCE LA English DT Article ID EMBRYONIC STEM-CELLS; SELF-RENEWAL; MOUSE; GLYCINE; CANCER; CHROMATIN AB Threonine is the only amino acid critically required for the pluripotency of mouse embryonic stem cells (mESCs), but the detailed mechanism remains unclear. We found that threonine and S-adenosylmethionine (SAM) metabolism are coupled in pluripotent stem cells, resulting in regulation of histone methylation. Isotope labeling of mESCs revealed that threonine provides a substantial fraction of both the cellular glycine and the acetyl-coenzyme A (CoA) needed for SAM synthesis. Depletion of threonine from the culture medium or threonine dehydrogenase (Tdh) from mESCs decreased accumulation of SAM and decreased trimethylation of histone H3 lysine 4 (H3K4me3), leading to slowed growth and increased differentiation. Thus, abundance of SAM appears to influence H3K4me3, providing a possible mechanism by which modulation of a metabolic pathway might influence stem cell fate. C1 [Ng Shyh-Chang; Teo, Ren Yi; Ratanasirintrawoot, Sutheera; Zhang, Jin; Onder, Tamer; Unternaehrer, Juli J.; Zhu, Hao; Daley, George Q.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Div Pediat Hematol & Oncol, Stem Cell Transplantat Program, Boston, MA 02115 USA. [Ng Shyh-Chang; Teo, Ren Yi; Ratanasirintrawoot, Sutheera; Zhang, Jin; Onder, Tamer; Unternaehrer, Juli J.; Zhu, Hao; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ng Shyh-Chang; Ratanasirintrawoot, Sutheera; Zhang, Jin; Onder, Tamer; Unternaehrer, Juli J.; Zhu, Hao; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Ng Shyh-Chang; Ratanasirintrawoot, Sutheera; Zhang, Jin; Onder, Tamer; Unternaehrer, Juli J.; Zhu, Hao; Daley, George Q.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Ng Shyh-Chang; Daley, George Q.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. [Ng Shyh-Chang; Locasale, Jason W.; Lyssiotis, Costas A.; Zheng, Yuxiang; Asara, John M.; Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Dept Med, Boston, MA 02215 USA. [Ng Shyh-Chang; Locasale, Jason W.; Lyssiotis, Costas A.; Zheng, Yuxiang; Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Div Pediat Hematol & Oncol, Stem Cell Transplantat Program, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu; lewis_cantley@hms.harvard.edu RI Onder, Tamer /H-3330-2013; Cantley, Lewis/D-1800-2014; OI Onder, Tamer /0000-0002-2372-9158; Cantley, Lewis/0000-0002-1298-7653; Zhu, Hao/0000-0002-8417-9698; Shyh-Chang, Ng/0000-0003-3138-9525; Locasale, Jason/0000-0002-7766-3502 FU NSS Scholarship from the Agency for Science, Technology and Research, Singapore; American Cancer Society; NIH [4R00CA168997-02, RC2HL102815, U01 HL100001, R01 GM56203]; Damon Runyon Cancer Research Foundation Amgen fellowship; iPierian Inc. FX We thank members of the Daley and Cantley labs for helpful discussions. Supported by the NSS Scholarship from the Agency for Science, Technology and Research, Singapore (N.S.-C.), the American Cancer Society and NIH grant 4R00CA168997-02 (J.W.L.), a Damon Runyon Cancer Research Foundation Amgen fellowship (C. A. L.), NIH grants RC2HL102815 and U01 HL100001 (G. Q. D.), and NIH grant R01 GM56203 (L. C. C.). G. Q. D. is an investigator of the HHMI. G. Q. D., as a co-founder and scientific advisory board member, holds stock options and receives consulting fees from iPierian Inc., a biopharmaceutical company that uses iPS cells in drug discovery against neurologic disease. L. C. C. is the founder and a member of the board of directors of Agios Pharmaceuticals, a company that targets metabolic enzymes for cancer treatment. NR 24 TC 166 Z9 168 U1 5 U2 84 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JAN 11 PY 2013 VL 339 IS 6116 BP 222 EP 226 DI 10.1126/science.1226603 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 067XI UT WOS:000313328200049 PM 23118012 ER PT J AU Shi, Y Frost, P Hoang, B Yang, Y Fukunaga, R Gera, J Lichtenstein, A AF Shi, Y. Frost, P. Hoang, B. Yang, Y. Fukunaga, R. Gera, J. Lichtenstein, A. TI MNK kinases facilitate c-myc IRES activity in rapamycin-treated multiple myeloma cells SO ONCOGENE LA English DT Article DE multiple myeloma; rapamycin; mTOR inhibitors; c-myc; IRES activity; MNK kinases ID INTERNAL RIBOSOME ENTRY; INITIATION-FACTOR 4E; MAMMALIAN TARGET; CYCLIN D1; ENHANCED SENSITIVITY; PROTEIN-SYNTHESIS; BINDING-PROTEIN; SITE FUNCTION; AKT ACTIVITY; N-TERMINI AB When mTOR inhibitor rapalogs prevent cap-dependent translation of cell-cycle proteins like c-myc, continuing tumor cell growth depends on cap-independent translation, which is mediated by internal ribosome entry sites (IRESes) located in the 5'-UTR (untranslated region) of transcripts. To investigate if rapalog-induced activation of MNK kinases had a role in such IRES activity, we studied multiple myeloma (MM) cells. Rapamycin (RAP)-activated MNK1 kinase activity in MM cell lines and primary specimens by a mitogen-activated protein kinase-dependent mechanism. Pharmacological inhibition of MNK activity or genetic silencing of MNK1 prevented a rapalog-induced upregulation of c-myc IRES activity. Although RAP, used alone, had little effect on myc protein expression, when combined with a MNK inhibitor, myc protein expression was abrogated. In contrast, there was no inhibition of myc RNA, consistent with an effect on myc translation. In a RAP-resistant MM cell lines as well as a resistant primary MM specimen, co-exposure to a MNK inhibitor or MNK1 knockdown significantly sensitized cells for RAP-induced cytoreduction. Studies in MNK-null murine embryonic fibroblasts additionally supported a role for MNK kinases in RAP-induced myc IRES stimulation. These results indicate that MNK kinase activity has a critical role in the fail-safe mechanism of IRES-dependent translation when mTOR is inhibited. As kinase activity also regulated sensitivity to RAP, the data also provide a rationale for therapeutically targeting MNK kinases for combined treatment with mTOR inhibitors. Oncogene (2013) 32, 190-197; doi:10.1038/onc.2012.43; published online 27 February 2012 C1 [Shi, Y.; Frost, P.; Hoang, B.; Yang, Y.; Fukunaga, R.; Gera, J.; Lichtenstein, A.] Univ Calif Los Angeles, Med Ctr, Dept Med, Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA 90024 USA. [Shi, Y.; Frost, P.; Hoang, B.; Yang, Y.; Fukunaga, R.; Gera, J.; Lichtenstein, A.] Univ Calif Los Angeles, Med Ctr, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Shi, Y.; Frost, P.; Hoang, B.; Yang, Y.; Fukunaga, R.; Gera, J.; Lichtenstein, A.] Osaka Univ Pharmaceut Sci, Dept Biochem, Biochem Lab, Takatsuki, Osaka, Japan. RP Lichtenstein, A (reprint author), W LA VA Hosp, W111H,11301 Wilshire Blvd,Bldg 500,Rm 4237, Los Angeles, CA 90073 USA. EM alan.lichtenstein@med.va.gov OI Frost, Patrick/0000-0003-3348-5983 FU Veteran's Administration; Multiple Myeloma Research Foundation; Department of Defense; NIH [RO1 CA109312, RO1 CA111448] FX We thank the UCLA Jonsson Comprehensive Cancer Center vector core lab for assistance in generating the lentiviral shRNA vectors. This work was supported by research funds of the Veteran's Administration, the Multiple Myeloma Research Foundation and the Department of Defense and NIH Grants RO1 CA109312 and RO1 CA111448. NR 32 TC 12 Z9 14 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 10 PY 2013 VL 32 IS 2 BP 190 EP 197 DI 10.1038/onc.2012.43 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 078CK UT WOS:000314075500007 PM 22370634 ER PT J AU Wu, DM Kraut, JA Abraham, WM AF Wu, Dongmei Kraut, Jeffrey A. Abraham, William M. TI Sabiporide Improves Cardiovascular Function, Decreases the Inflammatory Response and Reduces Mortality in Acute Metabolic Acidosis in Pigs SO PLOS ONE LA English DT Article ID EXTRACELLULAR ACIDOSIS; EXCHANGE INHIBITION; SODIUM-BICARBONATE; LACTIC-ACIDOSIS; MECHANISMS; CONTRACTILITY; MYOCARDIUM; ACTIVATION; MANAGEMENT; DIAGNOSIS AB Introduction: Acute metabolic acidosis impairs cardiovascular function and increases the mortality of critically ill patients. However, the precise mechanism(s) underlying these effects remain unclear. We hypothesized that targeting pH-regulatory protein, Na+/H+ exchanger (NHE1) could be a novel approach for the treatment of acute metabolic acidosis. The aim of the present study was to examine the impact of a novel NHE1 inhibitor, sabiporide, on cardiovascular function, blood oxygen transportation, and inflammatory response in an experimental model of metabolic acidosis produced by hemorrhage-induced hypovolemia followed by an infusion of lactic acid. Methods and Results: Anesthetized pigs were subjected to hypovolemia for 30 minutes. The animals then received a bolus infusion of sabiporide (3 mg/kg) or vehicle, followed by an infusion of lactic acid for 2 hours. The animals were continuously monitored for additional 3 hours. Hypovolemia followed by a lactic acid infusion resulted in a severe metabolic acidosis with blood pH falling to 6.8. In association with production of the acidemia, there was an excessive increase in pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR). Treatment with sabiporide significantly attenuated the increase in PAP by 38% and PVR by 67%, as well as significantly improved cardiac output by 51%. Sabiporide treatment also improved mixed venous blood oxygen saturation (55% in sabiporide group vs. 28% in control group), and improved systemic blood oxygen delivery by 36%. In addition, sabiporide treatment reduced plasma levels of TNF-alpha (by 33%), IL-6 (by 63%), troponin-I (by 54%), ALT (by 34%), AST (by 35%), and urea (by 40%). Conclusion: These findings support the possible beneficial effects of sabiporide in the treatment of acute metabolic acidosis and could have implications for the treatment of metabolic acidosis in man. C1 [Wu, Dongmei] Mt Sinai Med Ctr, Dept Res, Div Neonatol, Miami Beach, FL 33140 USA. [Abraham, William M.] Mt Sinai Med Ctr, Div Pulm & Crit Care Med, Miami Beach, FL 33140 USA. [Wu, Dongmei] Chonbuk Natl Univ, Dept BIN Fus Technol, Jeonju, South Korea. [Kraut, Jeffrey A.] Vet Adm Greater Angeles Healthcare Syst, Div Nephrol Med & Res Serv, Los Angeles, CA USA. [Kraut, Jeffrey A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Wu, DM (reprint author), Mt Sinai Med Ctr, Dept Res, Div Neonatol, Miami Beach, FL 33140 USA. EM dongmeiwu@bellsouth.net FU USAMRMC [W81XWH-06-1-0719]; Ministry of Education, Science and Technology [R31-20029, 2012007331]; National Research Foundation of Korea (NRF); honbuk National University, Korea FX This work was supported by a USAMRMC grant W81XWH-06-1-0719 (to DW); and in part by the World Class University Program (R31-20029) funded by the Ministry of Education, Science and Technology; by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012007331); and by New Faculty funding from Chonbuk National University, Korea. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 7 Z9 8 U1 0 U2 21 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 10 PY 2013 VL 8 IS 1 AR e53932 DI 10.1371/journal.pone.0053932 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 070YV UT WOS:000313552400061 PM 23326542 ER PT J AU Diogo, D Kurreeman, F Stahl, EA Liao, KP Gupta, N Greenberg, JD Rivas, MA Hickey, B Flannick, J Thomson, B Guiducci, C Ripke, S Adzhubey, I Barton, A Kremer, JM Alfredsson, L Sunyaev, S Martin, J Zhernakova, A Bowes, J Eyre, S Siminovitch, KA Gregersen, PK Worthington, J Klareskog, L Padyukov, L Raychaudhuri, S Plenge, RM AF Diogo, Dorothee Kurreeman, Fina Stahl, Eli A. Liao, Katherine P. Gupta, Namrata Greenberg, Jeffrey D. Rivas, Manuel A. Hickey, Brendan Flannick, Jason Thomson, Brian Guiducci, Candace Ripke, Stephan Adzhubey, Ivan Barton, Anne Kremer, Joel M. Alfredsson, Lars Sunyaev, Shamil Martin, Javier Zhernakova, Alexandra Bowes, John Eyre, Steve Siminovitch, Katherine A. Gregersen, Peter K. Worthington, Jane Klareskog, Lars Padyukov, Leonid Raychaudhuri, Soumya Plenge, Robert M. CA Consortium Rheumatology Rheumatoid Arthrit Consortium Int TI Rare, Low-Frequency, and Common Variants in the Protein-Coding Sequence of Biological Candidate Genes from GWASs Contribute to Risk of Rheumatoid Arthritis SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; INFLAMMATORY-BOWEL-DISEASE; COMPLEX TRAITS; LOCUS; HERITABILITY; AUTOIMMUNITY; METAANALYSIS; CORRECTS; LINKAGE; RECORDS AB The extent to which variants in the protein-coding sequence of genes contribute to risk of rheumatoid arthritis (RA) is unknown. In this study, we addressed this issue by deep exon sequencing and large-scale genotyping of 25 biological candidate genes located within RA risk loci discovered by genome-wide association studies (GWASs). First, we assessed the contribution of rare coding variants in the 25 genes to the risk of RA in a pooled sequencing study of 500 RA cases and 650 controls of European ancestry. We observed an accumulation of rare nonsynonymous variants exclusive to RA cases in IL2RA and IL2RB (burden test: p = 0.007 and p = 0.018, respectively). Next, we assessed the aggregate contribution of low-frequency and common coding variants to the risk of RA by dense genotyping of the 25 gene loci in 10,609 RA cases and 35,605 controls. We observed a strong enrichment of coding variants with a nominal signal of association with RA (p < 0.05) after adjusting for the best signal of association at the loci (P-enrichment = 6.4 x 10(-4)). For one locus containing CD2, we found that a missense variant, rs699738 (c.798C>A [p.His266Gln]), and a noncoding variant, rs624988, reside on distinct haplotypes and independently contribute to the risk of RA (p = 4.6 x 10(-6)). Overall, our results indicate that variants (distributed across the allele-frequency spectrum) within the protein-coding portion of a subset of biological candidate genes identified by GWASs contribute to the risk of RA. Further, we have demonstrated that very large sample sizes will be required for comprehensively identifying the independent alleles contributing to the missing heritability of RA. C1 [Diogo, Dorothee; Kurreeman, Fina; Stahl, Eli A.; Liao, Katherine P.; Hickey, Brendan; Raychaudhuri, Soumya; Plenge, Robert M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Diogo, Dorothee; Kurreeman, Fina; Stahl, Eli A.; Adzhubey, Ivan; Sunyaev, Shamil; Raychaudhuri, Soumya; Plenge, Robert M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Diogo, Dorothee; Kurreeman, Fina; Stahl, Eli A.; Rivas, Manuel A.; Flannick, Jason; Thomson, Brian; Guiducci, Candace; Ripke, Stephan; Sunyaev, Shamil; Raychaudhuri, Soumya; Plenge, Robert M.] Broad Inst, Med & Populat Genet Program, Cambridge, MA 02142 USA. [Gupta, Namrata] Gen Platform Broad Inst, Cambridge, MA 02142 USA. [Greenberg, Jeffrey D.] NYU, Hosp Joint Dis, New York, NY 10003 USA. [Flannick, Jason] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Flannick, Jason] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Ripke, Stephan] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Ripke, Stephan] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Ripke, Stephan] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Barton, Anne; Bowes, John; Eyre, Steve; Worthington, Jane; Raychaudhuri, Soumya] Univ Manchester, Manchester Acad Hlth Sci Ctr, Arthrit Res UK Epidemiol Unit, Manchester M13 9PT, Lancs, England. [Kremer, Joel M.] Ctr Rheumatol, Albany, NY 12206 USA. [Alfredsson, Lars] Karolinska Inst, Inst Environm Med, S-17177 Stockholm, Sweden. [Martin, Javier] CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada 18100, Spain. [Kurreeman, Fina; Zhernakova, Alexandra] Leiden Univ, Med Ctr, Dept Rheumatol, NL-2300 RC Leiden, Netherlands. [Zhernakova, Alexandra] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands. [Zhernakova, Alexandra] Univ Groningen, NL-9700 RB Groningen, Netherlands. [Siminovitch, Katherine A.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Siminovitch, Katherine A.] Univ Toronto, Dept Med, Toronto, ON M5G 1X5, Canada. [Gregersen, Peter K.] N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY 11030 USA. [Klareskog, Lars; Padyukov, Leonid] Karolinska Inst, Dept Med, Rheumatol Unit, S-17176 Stockholm, Sweden. [Klareskog, Lars; Padyukov, Leonid] Karolinska Univ Hosp Solna, S-17176 Stockholm, Sweden. RP Plenge, RM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. EM rplenge@partners.org RI Siminovitch, Katherine/K-1475-2013; Worthington, Jane/M-9770-2014; Barton, Anne/N-2053-2014; Bowes, John/B-3472-2015; Martin, Javier/B-8141-2008; OI Klareskog, Lars/0000-0001-9601-6186; Worthington, Jane/0000-0003-0544-042X; Zhernakova, Alexandra/0000-0002-4574-0841; Alfredsson, Lars/0000-0003-1688-6697; Eyre, Stephen/0000-0002-1251-6974; Barton, Anne/0000-0003-3316-2527; Bowes, John/0000-0003-4659-031X; Padyukov, Leonid/0000-0003-2950-5670 FU National Institutes of Health (NTH) [R01-AR057108, R01-AR056768, U01-GM092691, R01-AR059648]; Burroughs Wellcome Fund; European Union; NIH [K08AR060257, U54-LM008748]; European Research Council; Swedish Research Council [521-2009-3185] FX R.M.P. is supported by National Institutes of Health (NTH) grants R01-AR057108, R01-AR056768, U01-GM092691, and R01-AR059648 and holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund. F.K. was supported by a European Union international outgoing fellowship. K.P.L. is supported by NIH K08AR060257 Immunochip genotype data from the i2b2 samples and electronic-medical-record dataset were funded in part by NIH grant U54-LM008748. K.A.S. holds the Sherman Family Chair in Genomic Medicine and a Tier 1 Canada Research Chair. L.K. is supported by a grant from the European Research Council. L.P. is supported by Swedish Research Council grant 521-2009-3185. NR 56 TC 50 Z9 52 U1 1 U2 19 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JAN 10 PY 2013 VL 92 IS 1 BP 15 EP 27 DI 10.1016/j.ajhg.2012.11.012 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 073RA UT WOS:000313759000002 PM 23261300 ER PT J AU Michelson, AD AF Michelson, Alan D. TI Gray platelet syndrome SO BLOOD LA English DT Editorial Material C1 Harvard Univ, Boston Childrens Hosp, Dana Farber Canc Inst, Sch Med, Cambridge, MA 02138 USA. RP Michelson, AD (reprint author), Harvard Univ, Boston Childrens Hosp, Dana Farber Canc Inst, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 2 Z9 2 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 10 PY 2013 VL 121 IS 2 BP 250 EP 250 DI 10.1182/blood-2012-09-455550 PG 1 WC Hematology SC Hematology GA 073EN UT WOS:000313726400004 PM 23427340 ER PT J AU Parkin, B Ouillette, P Li, YF Keller, J Lam, C Roulston, D Li, C Shedden, K Malek, SN AF Parkin, Brian Ouillette, Peter Li, Yifeng Keller, Jennifer Lam, Cindy Roulston, Diane Li, Cheng Shedden, Kerby Malek, Sami N. TI Clonal evolution and devolution after chemotherapy in adult acute myelogenous leukemia SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; COPY NUMBER; LYMPHOBLASTIC-LEUKEMIA; SOMATIC MUTATIONS; INITIATING CELLS; DNMT3A MUTATIONS; FLT3 MUTATIONS; RELAPSE; DIAGNOSIS; AML AB The frequent occurrence of persistent or relapsed disease after induction chemotherapy in AML necessitates a better understanding of the clonal relationship of AML in various disease phases. In this study, we used SNP 6.0 array-based genomic profiling of acquired copy number aberrations (aCNA) and copy neutral LOH (cnLOH) together with sequence analysis of recurrently mutated genes to characterize paired AML genomes. We analyzed 28 AML sample pairs from patients who achieved complete remission with chemotherapy and subsequently relapsed and 11 sample pairs from patients with persistent disease after induction chemotherapy. Through review of aCNA/cnLOH and gene mutation profiles in informative cases, we demonstrate that relapsed AML invariably represents re-emergence or evolution of a founder clone. Furthermore, all individual aCNA or cnLOH detected at presentation persisted at relapse indicating that this lesion type is proximally involved in AML evolution. Analysis of informative paired persistent AML disease samples uncovered cases with 2 coexisting dominant clones of which at least one was chemotherapy sensitive and one resistant, respectively. These data support the conclusion that incomplete eradication of AML founder clones rather than stochastic emergence of fully unrelated novel clones underlies AML relapse and persistence with direct implications for clinical AML research. (Blood. 2013;121(2):369-377) C1 [Parkin, Brian; Ouillette, Peter; Li, Yifeng; Malek, Sami N.] Univ Michigan, Div Hematol & Oncol, Dept Internal Med, Ann Arbor, MI 48109 USA. [Keller, Jennifer; Lam, Cindy; Roulston, Diane] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Li, Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Li, Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Shedden, Kerby] Univ Michigan, Dept Stat, Ann Arbor, MI 48109 USA. RP Malek, SN (reprint author), Univ Michigan, Div Hematol & Oncol, Dept Internal Med, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM smalek@med.umich.edu FU Scholars in Clinical Research Program of the Leukemia & Lymphoma Society of America; National Institutes of Health through the University of Michigan's Cancer Center [5 P30 CA46592]; Oncology Research Training Grant [T32 CA 009357-30] FX This work was supported by the Scholars in Clinical Research Program of the Leukemia & Lymphoma Society of America (S.M.). This research is supported (in part) by the National Institutes of Health through the University of Michigan's Cancer Center Support Grant (5 P30 CA46592) and Oncology Research Training Grant (T32 CA 009357-30). NR 46 TC 29 Z9 32 U1 1 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 10 PY 2013 VL 121 IS 2 BP 369 EP 377 DI 10.1182/blood-2012-04-427039 PG 9 WC Hematology SC Hematology GA 073EN UT WOS:000313726400017 PM 23175688 ER PT J AU Shoag, J Haq, R Zhang, MF Liu, L Rowe, GC Jiang, AH Koulisis, N Farrel, C Amos, CI Wei, QY Lee, JE Zhang, JW Kupper, TS Qureshi, AA Cui, RT Han, JL Fisher, DE Arany, Z AF Shoag, Jonathan Haq, Rizwan Zhang, Mingfeng Liu, Laura Rowe, Glenn C. Jiang, Aihua Koulisis, Nicole Farrel, Caitlin Amos, Christopher I. Wei, Qingyi Lee, Jeffrey E. Zhang, Jiangwen Kupper, Thomas S. Qureshi, Abrar A. Cui, Rutao Han, Jiali Fisher, David E. Arany, Zoltan TI PGC-1 Coactivators Regulate MITF and the Tanning Response SO MOLECULAR CELL LA English DT Article ID MICROPHTHALMIA TRANSCRIPTION FACTOR; CUTANEOUS MALIGNANT-MELANOMA; SKIN PIGMENTATION; PROGNOSTIC MARKER; MASTER REGULATOR; PGC-1-ALPHA; CELLS; MOUSE; MELANOCYTES; METABOLISM AB The production of pigment by melanocytes tans the skin and protects against skin cancers. UV-exposed keratinocytes secrete alpha-MSH, which then activates melanin formation in melanocytes by inducing the microphthalmia-associated transcription factor (MITF). We show that PPAR-gamma coactivator (PGC)-1 alpha and PGC-1 beta are critical components of this melanogenic system in melanocytes. alpha-MSH signaling strongly induces PGC-1 alpha expression and stabilizes both PGC-1 alpha and PGC-1 beta proteins. The PGC-1s in turn activate the MITF promoter, and their expression correlates strongly with that of MITF in human melanoma cell lines and biopsy specimens. Inhibition of PGC-1 alpha and PGC-1 beta blocks the alpha-MSH-mediated induction of MITF and melanogenic genes. Conversely, overexpression of PGC-1 alpha induces pigment formation in cell culture and transgenic animals. Finally, polymorphism studies reveal expression quantitative trait loci in the PGC-1 beta gene that correlate with tanning ability and protection from melanoma in humans. These data identify PGC-1 coactivators as regulators of human tanning. C1 [Shoag, Jonathan; Liu, Laura; Rowe, Glenn C.; Jiang, Aihua; Koulisis, Nicole; Farrel, Caitlin; Arany, Zoltan] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02115 USA. [Haq, Rizwan; Fisher, David E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02115 USA. [Zhang, Mingfeng; Kupper, Thomas S.; Qureshi, Abrar A.; Han, Jiali] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Zhang, Mingfeng; Kupper, Thomas S.; Qureshi, Abrar A.; Han, Jiali] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Shoag, Jonathan] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Shoag, Jonathan] Harvard Univ, Sch Med, Cambridge, MA 02139 USA. [Haq, Rizwan; Fisher, David E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Zhang, Jiangwen] Harvard Univ, Fac Arts & Sci, Cambridge, MA 02138 USA. [Amos, Christopher I.; Wei, Qingyi] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Lee, Jeffrey E.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Cui, Rutao] Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. [Han, Jiali] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Fisher, David E.; Arany, Zoltan] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Arany, Z (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02115 USA. EM zarany@bidmc.harvard.edu FU American Heart Association; Harvard-MIT Division of Health Sciences and Technology; American Skin Association; National Institutes of Health; Doris Duke Medical Foundation; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; United States-Israel Binational Science Foundation; Smith Family Foundation; Harvard Stem Cell Institute; Ellison Medical Foundation Aging Program FX Support was provided by the American Heart Association (J.S.), the Harvard-MIT Division of Health Sciences and Technology (J.S.), the American Skin Association (R.H.), the National Institutes of Health (D.E.F., J.H., and Z.A.), the Doris Duke Medical Foundation (D.E.F.), the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (D.E.F.), the United States-Israel Binational Science Foundation (D.E.F.), the Smith Family Foundation (Z.A.), the Harvard Stem Cell Institute (Z.A.), and the Ellison Medical Foundation Aging Program (Z.A.). NR 57 TC 26 Z9 28 U1 2 U2 18 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JAN 10 PY 2013 VL 49 IS 1 BP 145 EP 157 DI 10.1016/j.molcel.2012.10.027 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 071PS UT WOS:000313607300014 PM 23201126 ER PT J AU Choueiri, TK Vaishampayan, U Rosenberg, JE Logan, TF Harzstark, AL Bukowski, RM Rini, BI Srinivas, S Stein, MN Adams, LM Ottesen, LH Laubscher, KH Sherman, L McDermott, DF Haas, NB Flaherty, KT Ross, R Eisenberg, P Meltzer, PS Merino, MJ Bottaro, DP Linehan, WM Srinivasan, R AF Choueiri, Toni K. Vaishampayan, Ulka Rosenberg, Jonathan E. Logan, Theodore F. Harzstark, Andrea L. Bukowski, Ronald M. Rini, Brian I. Srinivas, Sandy Stein, Mark N. Adams, Laurel M. Ottesen, Lone H. Laubscher, Kevin H. Sherman, Laurie McDermott, David F. Haas, Naomi B. Flaherty, Keith T. Ross, Robert Eisenberg, Peter Meltzer, Paul S. Merino, Maria J. Bottaro, Donald P. Linehan, W. Marston Srinivasan, Ramaprasad TI Phase II and Biomarker Study of the Dual MET/VEGFR2 Inhibitor Foretinib in Patients With Papillary Renal Cell Carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MET PROTOONCOGENE; INTERFERON-ALPHA; C-MET; SUNITINIB; EFFICACY; CANCER; TUMORS; SORAFENIB; MUTATIONS; THERAPIES AB Purpose Foretinib is an oral multikinase inhibitor targeting MET, VEGF, RON, AXL, and TIE-2 receptors. Activating mutations or amplifications in MET have been described in patients with papillary renal cell carcinoma (PRCC). We aimed to evaluate the efficacy and safety of foretinib in patients with PRCC. Patients and Methods Patients were enrolled onto the study in two cohorts with different dosing schedules of foretinib: cohort A, 240 mg once per day on days 1 through 5 every 14 days (intermittent arm); cohort B, 80 mg daily (daily dosing arm). Patients were stratified on the basis of MET pathway activation (germline or somatic MET mutation, MET [7q31] amplification, or gain of chromosome 7). The primary end point was overall response rate (ORR). Results Overall, 74 patients were enrolled, with 37 in each dosing cohort. ORR by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 was 13.5%, median progression-free survival was 9.3 months, and median overall survival was not reached. The presence of a germline MET mutation was highly predictive of a response (five of 10 v five of 57 patients with and without germline MET mutations, respectively). The most frequent adverse events of any grade associated with foretinib were fatigue, hypertension, gastrointestinal toxicities, and nonfatal pulmonary emboli. Conclusion Foretinib demonstrated activity in patients with advanced PRCC with a manageable toxicity profile and a high response rate in patients with germline MET mutations. J Clin Oncol 31:181-186. (C) 2012 by American Society of Clinical Oncology C1 [Choueiri, Toni K.; Rosenberg, Jonathan E.; Ross, Robert] Dana Farber Canc Inst, Boston, MA 02115 USA. [McDermott, David F.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Vaishampayan, Ulka] Karmanos Canc Inst, Detroit, MI USA. [Logan, Theodore F.] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. [Harzstark, Andrea L.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Srinivas, Sandy] Stanford Univ, Stanford Comprehens Canc Ctr, Stanford, CA 94305 USA. [Eisenberg, Peter] Calif Canc Care, Greenbrae, CA USA. [Bukowski, Ronald M.; Rini, Brian I.] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Stein, Mark N.] Canc Inst New Jersey, New Brunswick, NJ USA. [Haas, Naomi B.; Flaherty, Keith T.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Srinivasan, Ramaprasad] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Srinivasan, R (reprint author), NCI, Urol Oncol Branch, 9000 Rockville Pike,Bldg 10,Room 1-5940, Bethesda, MD 20892 USA. EM ramasrin@mail.nih.gov RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research; GlaxoSmithKline; Exelixis; Pfizer; Abbott Laboratories; Abraxis BioScience; Argos Therapeutics; AstraZeneca; BioVex; Bristol-Myers Squibb; Celgene; Chiron; Eli Lilly; EntreMed; immatics biotechnologies; Medlmmune; Novartis; Roche; Schering-Plough; Synta Pharmaceuticals; Wyeth; Prometheus Laboratories FX Supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research; by GlaxoSmithKline; and by Exelixis. Editorial support was provided by MediTech Media and was funded by GlaxoSmithKline.; Research Funding: Toni K. Choueiri, Pfizer; Theodore F. Logan, Abbott Laboratories, Abraxis BioScience, Argos Therapeutics, AstraZeneca, BioVex, Bristol-Myers Squibb, Celgene, Chiron, Eli Lilly, EntreMed, Exelixis, GlaxoSmithKline, immatics biotechnologies, Medlmmune, Novartis, Pfizer, Roche, Schering-Plough, Synta Pharmaceuticals, Wyeth; Brian I. Rini, GlaxoSmithKline; David F. McDermott, Prometheus Laboratories; Naomi B. Haas, GlaxoSmithKline, Novartis; Peter Eisenberg, GlaxoSmithKline NR 23 TC 138 Z9 141 U1 1 U2 18 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2013 VL 31 IS 2 BP 181 EP 186 DI 10.1200/JCO.2012.43.3383 PG 6 WC Oncology SC Oncology GA 068DQ UT WOS:000313345100010 PM 23213094 ER PT J AU Federico, M Rudiger, T Bellei, M Nathwani, BN Luminari, S Coiffier, B Harris, NL Jaffe, ES Pileri, SA Savage, KJ Weisenburger, DD Armitage, JO Mounier, N Vose, JM AF Federico, Massimo Rudiger, Thomas Bellei, Monica Nathwani, Bharat N. Luminari, Stefano Coiffier, Bertrand Harris, Nancy L. Jaffe, Elaine S. Pileri, Stefano A. Savage, Kerry J. Weisenburger, Dennis D. Armitage, James O. Mounier, Nicholas Vose, Julie M. TI Clinicopathologic Characteristics of Angioimmunoblastic T-Cell Lymphoma: Analysis of the International Peripheral T-Cell Lymphoma Project SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NON-HODGKINS-LYMPHOMA; LYMPHADENOPATHY; TRANSPLANTATION; DYSPROTEINEMIA; CLASSIFICATION; CHEMOTHERAPY; CYCLOSPORINE; MULTICENTER; EXPRESSION; DIAGNOSIS AB Purpose The International Peripheral T-Cell Lymphoma Project was undertaken to better understand the subtypes of T-cell and natural killer (NK) -cell lymphomas. Patients and Methods Angioimmunoblastic T-cell lymphoma (AITL) was diagnosed according to the 2001 WHO criteria by a central review process consisting of panels of expert hematopathologists. Clinical, pathologic, immunophenotyping, treatment, and survival data were correlated. Results Of 1,314 patients, 243 (18.5%) were diagnosed with AITL. At presentation, generalized lymphadenopathy was noted in 76% of patients, and 89% had stages III to IV disease. Skin rash was observed in 21% of patients. Hemolytic anemia and hypergammoglobulinemia occurred in 13% and 30% of patients, respectively. Five-year overall and failure-free survivals were 33% and 18%, respectively. At presentation, prognostic models were evaluated, including the standard International Prognostic Index, which comprised the following factors: age >= 60 years, stages III to IV disease, lactic dehydrogenase (LDH) > normal, extranodal sites (ENSs) > one, and performance status (PS) >= 2; the Prognostic Index for Peripheral T-Cell Lymphoma, comprising: age >= 60 years, PS >= 2, LDH > normal, and bone marrow involvement; and the alternative Prognostic Index for AITL (PIAI), comprising: age > 60 years, PS >= 2, ENSs > one, B symptoms, and platelet count < 150 x 10(9)/L. The simplified PIAI had a low-risk group (zero to one factors), with 5-year survival of 44%, and a high-risk group (two to five factors), with 5-year survival of 24% (P = .0065). Conclusion AITL is a rare clinicopathologic entity characterized by an aggressive course and dismal outcome with current therapies. J Clin Oncol 31:240-246. (C) 2012 by American Society of Clinical Oncology C1 [Federico, Massimo; Bellei, Monica; Luminari, Stefano] Univ Modena & Reggio Emilia, Modena, Italy. [Pileri, Stefano A.] Univ Bologna, Bologna, Italy. [Rudiger, Thomas] Stad Klinikum Karlsruhe, Karlsruhe, Germany. [Nathwani, Bharat N.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Nathwani, Bharat N.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Coiffier, Bertrand] Hosp Civils Lyon, Lyon, France. [Mounier, Nicholas] Hosp Archet, Nice, France. [Harris, Nancy L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Harris, Nancy L.] Harvard Univ, Sch Med, Boston, MA USA. [Jaffe, Elaine S.] NCI, Bethesda, MD 20892 USA. [Savage, Kerry J.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Vose, Julie M.] Univ Nebraska Med Ctr, Div Hematol Immunol, Omaha, NE 68198 USA. RP Vose, JM (reprint author), Univ Nebraska Med Ctr, Div Hematol Immunol, 987680 Nebraska Med Ctr, Omaha, NE 68198 USA. EM jmvose@unmc.edu RI luminari, stefano/J-5916-2014; Bellei, Monica/J-6052-2014; Federico, Massimo/J-5984-2014; Federico, Massimo/A-6801-2012; OI luminari, stefano/0000-0001-8446-2285; Bellei, Monica/0000-0001-7846-732X; Federico, Massimo/0000-0002-5074-3262; Federico, Massimo/0000-0002-9889-3796; Jaffe, Elaine/0000-0003-4632-0301 FU University of Nebraska Foundation, Omaha, NE; Fondazione Cassa di Risparmio di Modena, Modena, Italy; Associazione "Angela Serra" per la Ricerca sul Cancro, Modena, Italy FX Supported by grants from the University of Nebraska Foundation, Omaha, NE; Fondazione Cassa di Risparmio di Modena, Modena, Italy; and Associazione "Angela Serra" per la Ricerca sul Cancro, Modena, Italy. NR 39 TC 68 Z9 71 U1 0 U2 7 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2013 VL 31 IS 2 BP 240 EP 246 DI 10.1200/JCO.2011.37.3647 PG 7 WC Oncology SC Oncology GA 068DQ UT WOS:000313345100018 PM 22869878 ER PT J AU Morris, P AF Morris, Peter TI Joseph E. Murray (1919-2012) OBITUARY SO NATURE LA English DT Biographical-Item C1 [Morris, Peter] Univ Oxford, Oxford OX1 2JD, England. [Morris, Peter] Oxford Transplant Ctr, Oxford, England. [Morris, Peter] Royal Coll Surgeons England, Ctr Evidence Transplantat, London, England. [Morris, Peter] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Morris, P (reprint author), Univ Oxford, Oxford OX1 2JD, England. EM pmorris@rcseng.ac.uk NR 1 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JAN 10 PY 2013 VL 493 IS 7431 BP 164 EP 164 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 066YY UT WOS:000313259600021 PM 23302851 ER PT J AU Ryan, CJ Smith, MR de Bono, JS Molina, A Logothetis, CJ de Souza, P Fizazi, K Mainwaring, P Piulats, JM Ng, S Carles, J Mulders, PFA Basch, E Small, EJ Saad, F Schrijvers, D Van Poppel, H Mukherjee, SD Suttmann, H Gerritsen, WR Flaig, TW George, DJ Yu, EY Efstathiou, E Pantuck, A Winquist, E Higano, CS Taplin, ME Park, Y Kheoh, T Griffin, T Scher, HI Rathkopf, DE AF Ryan, Charles J. Smith, Matthew R. de Bono, Johann S. Molina, Arturo Logothetis, Christopher J. de Souza, Paul Fizazi, Karim Mainwaring, Paul Piulats, Josep M. Ng, Siobhan Carles, Joan Mulders, Peter F. A. Basch, Ethan Small, Eric J. Saad, Fred Schrijvers, Dirk Van Poppel, Hendrik Mukherjee, Som D. Suttmann, Henrik Gerritsen, Winald R. Flaig, Thomas W. George, Daniel J. Yu, Evan Y. Efstathiou, Eleni Pantuck, Allan Winquist, Eric Higano, Celestia S. Taplin, Mary-Ellen Park, Youn Kheoh, Thian Griffin, Thomas Scher, Howard I. Rathkopf, Dana E. CA COU-AA-302 Investigators TI Abiraterone in Metastatic Prostate Cancer without Previous Chemotherapy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HUMAN CYTOCHROME P450(17-ALPHA); STEROIDAL INHIBITORS; HORMONAL-THERAPY; CONTROLLED TRIAL; CLINICAL-TRIALS; END-POINTS; ACETATE; CARCINOMA; MITOXANTRONE; PREDNISONE AB BACKGROUND Abiraterone acetate, an androgen biosynthesis inhibitor, improves overall survival in patients with metastatic castration-resistant prostate cancer after chemotherapy. We evaluated this agent in patients who had not received previous chemotherapy. METHODS In this double-blind study, we randomly assigned 1088 patients to receive abiraterone acetate (1000 mg) plus prednisone (5 mg twice daily) or placebo plus prednisone. The coprimary end points were radiographic progression-free survival and overall survival. RESULTS The study was unblinded after a planned interim analysis that was performed after 43% of the expected deaths had occurred. The median radiographic progression-free survival was 16.5 months with abiraterone-prednisone and 8.3 months with prednisone alone (hazard ratio for abiraterone-prednisone vs. prednisone alone, 0.53; 95% confidence interval [CI], 0.45 to 0.62; P<0.001). Over a median follow-up period of 22.2 months, overall survival was improved with abiraterone-prednisone (median not reached, vs. 27.2 months for prednisone alone; hazard ratio, 0.75; 95% CI, 0.61 to 0.93; P = 0.01) but did not cross the efficacy boundary. Abiraterone-prednisone showed superiority over prednisone alone with respect to time to initiation of cytotoxic chemotherapy, opiate use for cancer-related pain, prostate-specific antigen progression, and decline in performance status. Grade 3 or 4 mineralocorticoid- related adverse events and abnormalities on liver-function testing were more common with abiraterone-prednisone. CONCLUSIONS Abiraterone improved radiographic progression-free survival, showed a trend toward improved overall survival, and significantly delayed clinical decline and initiation of chemotherapy in patients with metastatic castration-resistant prostate cancer. (Funded by Janssen Research and Development, formerly Cougar Biotechnology; ClinicalTrials.gov number, NCT00887198.) C1 [Ryan, Charles J.; Small, Eric J.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Smith, Matthew R.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Taplin, Mary-Ellen] Dana Farber Canc Inst, Boston, MA 02115 USA. [de Bono, Johann S.] Inst Canc Res, Sutton, Surrey, England. [de Bono, Johann S.] Royal Marsden Hosp, Sutton, Surrey, England. [Molina, Arturo; Park, Youn; Kheoh, Thian; Griffin, Thomas] Janssen Res & Dev, Los Angeles, CA USA. [Pantuck, Allan] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Logothetis, Christopher J.; Efstathiou, Eleni] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [de Souza, Paul] St George Private Hosp, Kogarah, NSW, Australia. [Mainwaring, Paul] Haematol & Oncol Clin Australia, Brisbane, Qld, Australia. [Ng, Siobhan] St John God Hosp, Subiaco, WA, Australia. [Fizazi, Karim] Univ Paris 11, Inst Gustave Roussy, Villejuif, France. [Piulats, Josep M.] Inst Catala Oncol Hosp, Barcelona, Spain. [Carles, Joan] Univ Vall dHebron, Barcelona, Spain. [Mulders, Peter F. A.] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Gerritsen, Winald R.] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. [Basch, Ethan; Scher, Howard I.; Rathkopf, Dana E.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Saad, Fred] Univ Montreal, Montreal, PQ, Canada. [Mukherjee, Som D.] Juravinski Canc Ctr, Hamilton Hlth Serv, Hamilton, ON, Canada. [Winquist, Eric] London Hlth Sci Ctr, London, ON, Canada. [Schrijvers, Dirk] Hosp Network Antwerp ZNA Middelheim, Antwerp, Belgium. [Van Poppel, Hendrik] Katholieke Univ Leuven Hosp, Louvain, Belgium. [Suttmann, Henrik] Urologikum Hamburg, Hamburg, Germany. [Flaig, Thomas W.] Univ Colorado, Ctr Canc, Aurora, CO USA. [George, Daniel J.] Duke Univ Hosp, Med Ctr, Durham, NC USA. [Yu, Evan Y.; Higano, Celestia S.] Univ Washington, Seattle, WA 98195 USA. [Efstathiou, Eleni] Univ Athens, Sch Med, Alexandra Hosp, Dept Clin Therapeut, GR-10679 Athens, Greece. RP Ryan, CJ (reprint author), UCSF Helen Diller Family Comprehens Canc Ctr, Genitourinary Med Oncol Program, 1600 Divisadero St, San Francisco, CA 94115 USA. EM ryanc@medicine.ucsf.edu RI Gerritsen, W.R./H-8031-2014; Mulders, Peter/H-8076-2014; OI Rathkopf, Dana/0000-0002-4503-7582; colombel, marc/0000-0002-0152-8021 FU Janssen Research and Development FX Supported by Ortho Biotech Oncology Research and Development, a unit of Cougar Biotechnology (now Janssen Research and Development). NR 26 TC 804 Z9 823 U1 11 U2 98 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 10 PY 2013 VL 368 IS 2 BP 138 EP 148 DI 10.1056/NEJMoa1209096 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 066RO UT WOS:000313238100004 PM 23228172 ER PT J AU Neumann, H Daly, MJ AF Neumann, Harald Daly, Mark J. TI Variant TREM2 as Risk Factor for Alzheimer's Disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID RECEPTOR; MUTATIONS; DAP12 C1 [Neumann, Harald] Univ Bonn, Inst Reconstruct Neurobiol, Bonn, Germany. [Daly, Mark J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. RP Neumann, H (reprint author), Univ Bonn, Inst Reconstruct Neurobiol, Bonn, Germany. RI Neumann, Harald/A-9718-2010 OI Neumann, Harald/0000-0002-5071-5202 NR 11 TC 51 Z9 53 U1 2 U2 25 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 10 PY 2013 VL 368 IS 2 BP 182 EP 184 DI 10.1056/NEJMe1213157 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 066RO UT WOS:000313238100010 PM 23151315 ER PT J AU Singhal, AB AF Singhal, Aneesh B. TI Case 31-2012: A Young Man with Neurologic Symptoms Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Singhal, AB (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 10 PY 2013 VL 368 IS 2 BP 194 EP 194 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 066RO UT WOS:000313238100031 PM 23301752 ER PT J AU van Rijn, S Nilsson, J Noske, DP Vandertop, WP Tannous, BA Wurdinger, T AF van Rijn, Sjoerd Nilsson, Jonas Noske, David P. Vandertop, W. Peter Tannous, Bakhos A. Wuerdinger, Thomas TI Functional multiplex reporter assay using tagged Gaussia luciferase SO SCIENTIFIC REPORTS LA English DT Article ID IN-VIVO; GENE-EXPRESSION; FLUORESCENT PROTEINS; CULTURE AB We have developed a multiplex reporter system to monitor multiple biological variables in real-time. The secreted Gaussia luciferase was fused to ten different epitope tags (Gluc(tag)), each expressed in different tumor cells. By immunobinding of the tags followed by Gluc(tag) detection, this system allowed the independent and real-time monitoring of mixed cell cultures in vitro and of mixed subcutaneous and intracranial tumor subpopulations in vivo. C1 [van Rijn, Sjoerd; Nilsson, Jonas; Noske, David P.; Vandertop, W. Peter; Wuerdinger, Thomas] Vrije Univ Amsterdam, Med Ctr, Neurooncol Res Grp, Dept Neurosurg,Canc Ctr Amsterdam, Amsterdam, Netherlands. [Nilsson, Jonas] Umea Univ, Dept Radiat Sci, Umea, Sweden. [Tannous, Bakhos A.; Wuerdinger, Thomas] Massachusetts Gen Hosp, Dept Neurol, Ctr Neurosci, Boston, MA 02114 USA. [Tannous, Bakhos A.; Wuerdinger, Thomas] Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. RP Wurdinger, T (reprint author), Vrije Univ Amsterdam, Med Ctr, Neurooncol Res Grp, Dept Neurosurg,Canc Ctr Amsterdam, Amsterdam, Netherlands. EM Jonas.nilsson@onkologi.umu.se; t.wurdinger@vumc.nl FU NWO-VIDI; NIH/NINDS [P30NS045776, R01NS064983]; CCA Fellowship; VICI Fellowship FX This work was supported partly by grants from NWO-VIDI (TW), and NIH/NINDS P30NS045776 and R01NS064983 (BAT). SVR and JN are supported by CCA/VICI Fellowships. We are thankful to Priscilla Jainandunsing, Laura Jonkman, Stephanie van Hoppe, Tonny Lagerweij and Laurine Wedekind for technical support. NR 17 TC 4 Z9 4 U1 0 U2 7 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 10 PY 2013 VL 3 AR 1046 DI 10.1038/srep01046 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 069EM UT WOS:000313418100001 PM 23308339 ER PT J AU Greer, DM Robbins, GK Lijewski, V Gonzales, RG McGuone, D AF Greer, David M. Robbins, Gregory K. Lijewski, Virginia Gonzales, R. Gilberto McGuone, Declan TI Case 1-2013: A 63-Year-Old Man with Paresthesias and Difficulty Swallowing SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HUMAN RABIES; MANAGEMENT; DIAGNOSIS; INDUCTION; BOTULISM; HUMANS; COMA C1 [Greer, David M.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. [Robbins, Gregory K.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Gonzales, R. Gilberto] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [McGuone, Declan] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Robbins, Gregory K.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Gonzales, R. Gilberto] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [McGuone, Declan] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Lijewski, Virginia] Massachusetts Dept Publ Hlth, Div Epidemiol & Immunizat, Boston, MA USA. RP Greer, DM (reprint author), Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. NR 19 TC 10 Z9 10 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 10 PY 2013 VL 368 IS 2 BP 172 EP 180 DI 10.1056/NEJMcpc1209935 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 066RO UT WOS:000313238100009 PM 23301735 ER PT J AU Duarte, M Wang, LL Calderwood, MA Adelmant, G Ohashi, M Roecklein-Canfield, J Marto, JA Hill, DE Deng, HY Johannsen, E AF Duarte, Melissa Wang, Lili Calderwood, Michael A. Adelmant, Guillaume Ohashi, Makoto Roecklein-Canfield, Jennifer Marto, Jarrod A. Hill, David E. Deng, Hongyu Johannsen, Eric TI An RS Motif within the Epstein-Barr Virus BLRF2 Tegument Protein Is Phosphorylated by SRPK2 and Is Important for Viral Replication SO PLOS ONE LA English DT Article ID MURINE GAMMAHERPESVIRUS-68; GENE-EXPRESSION; SM PROTEIN; KINASES; SEQUENCE; ORF52; IDENTIFICATION; HERPESVIRUS; ENRICHMENT; INHIBITION AB Epstein-Barr virus (EBV) is a gammaherpesvirus that causes infectious mononucleosis, B cell lymphomas, and nasopharyngeal carcinoma. Many of the genes required for EBV virion morphogenesis are found in all herpesviruses, but some are specific to gammaherpesviruses. One of these gamma-specific genes, BLRF2, encodes a tegument protein that has been shown to be essential for replication in other gammaherpesviruses. In this study, we identify BLRF2 interacting proteins using binary and co-complex protein assays. Serine/Arginine-rich Protein Kinase 2 (SRPK2) was identified by both assays and was further shown to phosphorylate an RS motif in the BLRF2 C-terminus. Mutation of this RS motif (S148A+S150A) abrogated the ability of BLRF2 to support replication of a murine gammaherpesvirus 68 genome lacking the BLRF2 homolog (ORF52). We conclude that the BLRF2 RS motif is phosphorylated by SRPK2 and is important for viral replication. C1 [Duarte, Melissa; Calderwood, Michael A.; Johannsen, Eric] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. [Duarte, Melissa; Calderwood, Michael A.; Roecklein-Canfield, Jennifer; Hill, David E.] Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA. [Duarte, Melissa; Calderwood, Michael A.; Roecklein-Canfield, Jennifer; Hill, David E.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Wang, Lili; Deng, Hongyu] Chinese Acad Sci, Inst Biophys, Key Lab Infect & Immun, Beijing 100080, Peoples R China. [Calderwood, Michael A.; Hill, David E.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Adelmant, Guillaume; Marto, Jarrod A.] Dana Farber Canc Inst, Blais Prote Ctr, Dept Canc Biol, Boston, MA 02115 USA. [Adelmant, Guillaume; Marto, Jarrod A.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Ohashi, Makoto; Johannsen, Eric] Univ Wisconsin, Dept Med, Madison, WI USA. [Roecklein-Canfield, Jennifer] Simmons Coll, Dept Chem & Phys, Boston, MA 02115 USA. RP Johannsen, E (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. EM ejohannsen@medicine.wisc.edu RI Hill, David/B-6617-2011; Calderwood, Mike/B-2475-2014; OI Calderwood, Mike/0000-0001-6475-1418; Wang, Lili/0000-0002-8315-531X FU Center of Excellence in Genomic Science (CEGS) grant from the National Human Genome Research Institute (NHGRI) [P50HG004233]; Howard Hughes Medical Institute Physician-Scientist Early Career Award; National Natural Science Foundation of China [30930007, 81171582] FX Melissa Duarte was post-baccalaureate trainee as part of a Center of Excellence in Genomic Science (CEGS) grant P50HG004233 from the National Human Genome Research Institute (NHGRI) awarded to Marc Vidal (PI). Eric Johannsen is the recipient of a Howard Hughes Medical Institute Physician-Scientist Early Career Award. Part of the research was supported by grants No. 30930007 and 81171582 from the National Natural Science Foundation of China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 43 TC 4 Z9 4 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 9 PY 2013 VL 8 IS 1 AR e53512 DI 10.1371/journal.pone.0053512 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 070YR UT WOS:000313551500079 PM 23326445 ER PT J AU Naranbhai, V Altfeld, M Karim, SSA Ndung'u, T Karim, QA Carr, WH AF Naranbhai, Vivek Altfeld, Marcus Karim, Salim S. Abdool Ndung'u, Thumbi Karim, Quarraisha Abdool Carr, William H. TI Changes in Natural Killer Cell Activation and Function during Primary HIV-1 Infection SO PLOS ONE LA English DT Article ID NK CELLS; VIREMIA; REPLICATION; RESPONSES; INNATE; BLOOD AB Background: Recent reports suggest that Natural Killer (NK) cells may modulate pathogenesis of primary HIV-1 infection. However, HIV dysregulates NK-cell responses. We dissected this bi-directional relationship to understand how HIV impacts NK-cell responses during primary HIV-1 infection. Methodology/Principal Findings: Paired samples from 41 high-risk, initially HIV-uninfected CAPRISA004 participants were analysed prior to HIV acquisition, and during viraemic primary HIV-1 infection. At the time of sampling post-infection five women were seronegative, 11 women were serodiscordant, and 25 women were seropositive by HIV-1 rapid immunoassay. Flow cytometry was used to measure NK and T-cell activation, NK-cell receptor expression, cytotoxic and cytokine-secretory functions, and trafficking marker expression (CCR7, alpha(4)beta(7)). Non-parametric statistical tests were used. Both NK cells and T-cells were significantly activated following HIV acquisition (p = 0.03 and p<0.0001, respectively), but correlation between NK-cell and T-cell activation was uncoupled following infection (pre-infection r = 0.68;p<0.0001; post-infection, during primary infection r = 0.074;p = 0.09). Nonetheless, during primary infection NK-cell and T-cell activation correlated with HIV viral load (r = 0.32'p = 0.04 and r = 0.35;p = 0.02, respectively). The frequency of Killer Immunoglobulin-like Receptor-expressing (KIRpos) NK cells increased following HIV acquisition (p = 0.006), and KIRpos NK cells were less activated than KIRneg NK cells amongst individuals sampled while seronegative or serodiscordant (p = 0.001;p<0.0001 respectively). During HIV-1 infection, cytotoxic NK cell responses evaluated after IL-2 stimulation alone, or after co-culture with 721 cells, were impaired (p = 0.006 and p = 0.002, respectively). However, NK-cell IFN-y secretory function was not significantly altered. The frequency of CCR7+ NK cells was elevated during primary infection, particularly at early time-points (p<0.0001). Conclusions/Significance: Analyses of immune cells before and after HIV infection revealed an increase in both NK-cell activation and KIR expression, but reduced cytotoxicity during acute infection. The increase in frequency of NK cells able to traffic to lymph nodes following HIV infection suggests that these cells may play a role in events in secondary lymphoid tissue. C1 [Naranbhai, Vivek; Karim, Salim S. Abdool; Karim, Quarraisha Abdool] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Doris Duke Med Res Inst, CAPRISA Ctr AIDS Programme Res S Africa, Durban, South Africa. [Naranbhai, Vivek; Altfeld, Marcus; Ndung'u, Thumbi; Carr, William H.] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa. [Altfeld, Marcus; Ndung'u, Thumbi; Carr, William H.] Massachusetts Gen Hosp, Massachusetts Inst Technol & Harvard, Ragon Inst, Boston, MA 02114 USA. [Karim, Salim S. Abdool; Karim, Quarraisha Abdool] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. RP Carr, WH (reprint author), Univ KwaZulu Natal, Nelson R Mandela Sch Med, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa. EM wcarr@mec.cuny.edu RI Abdool Karim, Salim Safurdeen/N-5947-2013; OI Abdool Karim, Salim Safurdeen/0000-0002-4986-2133; Naranbhai, Vivek/0000-0003-4281-8882; Ndung'u, Thumbi/0000-0003-2962-3992 FU South African HIV/AIDS Research Platform (SHARP); US National Institutes for Health [FIC K01-TW007793]; CONRAD, Eastern Virginia Medical School (USAID) [GP00-08-00005-00, PPA-09-046]; US National Institutes for Health's Comprehensive International Program of Research on AIDS (CIPRA) [AI51794]; LIFELab; Columbia University-South Africa Fogarty AIDS International Training and Research Program (AITRP) [D43 TW000231]; Massachusetts General Hospital Physician Scientist Development Award; South African National Research Foundation KISC Award FX This work was supported by the South African HIV/AIDS Research Platform (SHARP), and US National Institutes for Health FIC K01-TW007793. This study was part of the CAPRISA TRAPS (Tenofovir gel Research for AIDS Prevention Science) Program, which is funded by CONRAD, Eastern Virginia Medical School (USAID co-operative grant #GP00-08-00005-00, subproject agreement # PPA-09-046). The views expressed by the authors do not necessarily reflect the views of USAID, Gilead Sciences, Eastern Virginia Medical School or CONRAD. The authors thank the US National Institutes for Health's Comprehensive International Program of Research on AIDS (CIPRA grant # AI51794) for the research infrastructure. VN was supported by LIFELab and the Columbia University-South Africa Fogarty AIDS International Training and Research Program (AITRP, grant #D43 TW000231). MA is a Distinguished Clinical Scientist of the Doris Duke Charitable Foundation. WHC was supported by a Massachusetts General Hospital Physician Scientist Development Award. TN holds the South African Research Chair in Systems Biology of HIV/AIDS and is a Howard Hughes Medical Institute International Early Career Scientist. Additional training was supported by the South African National Research Foundation KISC Award. Gilead Sciences did not fund this project, however the drug used in the clinical trial from which samples were used for this study belongs to Gilead Sciences. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 28 TC 23 Z9 23 U1 0 U2 16 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 9 PY 2013 VL 8 IS 1 AR e53251 DI 10.1371/journal.pone.0053251 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 070YR UT WOS:000313551500056 PM 23326405 ER PT J AU Yamin, HG Stern, EA Cohen, D AF Yamin, Hagar G. Stern, Edward A. Cohen, Dana TI Parallel Processing of Environmental Recognition and Locomotion in the Mouse Striatum SO JOURNAL OF NEUROSCIENCE LA English DT Article ID TONICALLY ACTIVE NEURONS; FAST-SPIKING INTERNEURONS; MEDIUM SPINY NEURONS; BASAL GANGLIA; MONKEY STRIATUM; PROJECTION NEURONS; PRIMATE STRIATUM; GLOBUS-PALLIDUS; RAT NEOSTRIATUM; PHYSIOLOGICAL-PROPERTIES AB Information processing in behaving animals has been the target of many studies in the striatum; however, its dynamics and complexity remain to a large extent unknown. Here, we chronically recorded neuronal populations in dorsal striatum as mice were exposed to a novel environment, a paradigm which enables the dissociation of locomotion and environmental recognition. The findings indicate that non-overlapping populations of striatal projection neurons-the medium spiny neurons-reliably encode locomotion and environmental identity, whereas two subpopulations of short-spike interneurons encode distinct information: the fast spiking interneurons preferentially encode locomotion whereas the second type of interneurons preferentially encodes environmental identity. The three neuronal subgroups used cell-type specific coding schemes. This study provides evidence for the existence of parallel processing circuits within the sensorimotor region of the striatum. C1 [Yamin, Hagar G.; Stern, Edward A.; Cohen, Dana] Bar Ilan Univ, Leslie & Susan Gonda Multidisciplinary Brain Res, IL-52900 Ramat Gan, Israel. [Stern, Edward A.] Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Stern, Edward A.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Cohen, D (reprint author), Bar Ilan Univ, Leslie & Susan Gonda Multidisciplinary Brain Res, IL-52900 Ramat Gan, Israel. EM danacoh@gmail.com FU Israel Science Foundation (ISF) [861/06] FX This study was funded in part by the Israel Science Foundation (ISF) Grant861/06 (D. C.). We thank Osnat Bar-Shira and Dr. Gal Chechik for assistance with the SVM algorithm and Dr. Izhar Bar-Gad for useful comments on the manuscript. NR 82 TC 8 Z9 8 U1 1 U2 10 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 9 PY 2013 VL 33 IS 2 BP 473 EP 484 DI 10.1523/JNEUROSCI.4474-12.2013 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 071EN UT WOS:000313569600011 PM 23303928 ER PT J AU Westin, SN Mills, GB Myers, AP AF Westin, Shannon N. Mills, Gordon B. Myers, Andrea P. TI Repurposing the Pap Smear: One Step Closer to Gynecologic Cancer Screening SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID CELL-FREE DNA; ENDOMETRIAL CANCER; PAPANICOLAOU TESTS; OVARIAN-CANCER; CARCINOMA; IDENTIFICATION; MUTATIONS; CYTOLOGY; PLASMA; COHORT AB Prevention and early detection remain essential to decreasing cancer mortality. Screening DNA in Pap smears has the potential to increase the rate of early detection of endometrial and ovarian cancers. In this issue of Science Translational Medicine, Kinde and colleagues use advanced sequencing technology to evaluate DNA to screen for gynecologic malignancies. C1 [Westin, Shannon N.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA. [Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA. [Myers, Andrea P.] Dana Farber Canc Inst, Dept Med Oncol, Gynecol Oncol Program, Boston, MA 02215 USA. RP Westin, SN (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA. EM swestin@mdanderson.org FU NIH [2P50 CA098258-06]; Stand Up to Cancer Dream Team Translational Research Grant [SU2C-AACR-DT0209] FX NIH 2P50 CA098258-06 SPORE in Uterine Cancer; SU2C-AACR-DT0209 Stand Up to Cancer Dream Team Translational Research Grant. NR 19 TC 1 Z9 1 U1 1 U2 7 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD JAN 9 PY 2013 VL 5 IS 167 AR 167ps1 DI 10.1126/scitranslmed.3005411 PG 4 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 071ED UT WOS:000313568200001 PM 23303602 ER PT J AU Mizutari, K Fujioka, M Hosoya, M Bramhall, N Okano, HJ Okano, H Edge, ASB AF Mizutari, Kunio Fujioka, Masato Hosoya, Makoto Bramhall, Naomi Okano, Hirotaka James Okano, Hideyuki Edge, Albert S. B. TI Notch Inhibition Induces Cochlear Hair Cell Regeneration and Recovery of Hearing after Acoustic Trauma SO NEURON LA English DT Article ID MOUSE INNER-EAR; ROUND WINDOW MEMBRANE; STEM-CELLS; RETINOBLASTOMA PROTEIN; PROGENITOR CELLS; IN-VIVO; EXPRESSION; ORGAN; CORTI; FATE AB Hearing loss due to damage to auditory hair cells is normally irreversible because mammalian hair cells do not regenerate. Here, we show that new hair cells can be induced and can cause partial recovery of hearing in ears damaged by noise trauma, when Notch signaling is inhibited by a gamma-secretase inhibitor selected for potency in stimulating hair cell differentiation from inner ear stem cells in vitro. Hair cell generation resulted from an increase in the level of bHLH transcription factor Atoh1 in response to inhibition of Notch signaling. In vivo prospective labeling of Sox2-expressing cells with a Cre-lox system unambiguously demonstrated that hair cell generation resulted from transdifferentiation of supporting cells. Manipulating cell fate of cochlear sensory cells in vivo by pharmacological inhibition of Notch signaling is thus a potential therapeutic approach to the treatment of deafness. C1 [Mizutari, Kunio; Fujioka, Masato; Bramhall, Naomi; Edge, Albert S. B.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Mizutari, Kunio; Fujioka, Masato; Bramhall, Naomi; Edge, Albert S. B.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Tillotson Unit, Boston, MA 02114 USA. [Fujioka, Masato; Hosoya, Makoto; Okano, Hirotaka James; Okano, Hideyuki] Keio Univ, Sch Med, Dept Physiol, Tokyo 1608582, Japan. [Bramhall, Naomi; Edge, Albert S. B.] Harvard & MIT, Program Speech & Hearing Biosci & Technol, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Edge, ASB (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. EM albert_edge@meei.harvard.edu RI Hidokano, Hideyuki/J-5973-2013 FU National Institute on Deafness and other Communicative Disorders (NIDCD) [RO1 DC007174, R21 DC010440, P30 DC05209]; Tillotson Corporation; Shulsky Foundation; Mochida Memorial Foundation for Medical and Pharmaceutical Research; International Activities in Life Sciences and Medicine, Keio University Medical Science Fund FX We thank M.C. Liberman for critical comments on the manuscript. We thank Yukiko Watada and Yumi Matsuzaki for assistance. This work was supported by grants RO1 DC007174, R21 DC010440, and P30 DC05209 from the National Institute on Deafness and other Communicative Disorders (NIDCD); by the Tillotson Corporation, the Shulsky Foundation, and Robert Boucai; by the Mochida Memorial Foundation for Medical and Pharmaceutical Research; and by grants for International Activities in Life Sciences and Medicine, Keio University Medical Science Fund. NR 52 TC 99 Z9 108 U1 4 U2 62 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD JAN 9 PY 2013 VL 77 IS 1 BP 58 EP 69 DI 10.1016/j.neuron.2012.10.032 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 068ZL UT WOS:000313404600008 PM 23312516 ER PT J AU Fu, J Doshi, BN Oral, E Muratoglu, OK AF Fu, Jun Doshi, Brinda N. Oral, Ebru Muratoglu, Orhun K. TI High temperature melted, radiation cross-linked, vitamin E stabilized oxidation resistant UHMWPE with low wear and high impact strength SO POLYMER LA English DT Article DE UHMWPE; High temperature melting; Cross-linking ID MOLECULAR-WEIGHT POLYETHYLENE; ALPHA-TOCOPHEROL; IRRADIATED UHMWPE; GAMMA-IRRADIATION; OSTEOLYSIS; LINKING; ARTHROPLASTY; REPLACEMENTS; MODEL AB In a previous communication we showed improvement in the wear resistance and toughness of cross-linked ultrahigh molecular weight polyethylene (UHMWPE) for total joint implants by radiation cross-linking after high temperature melting (HTM). In this study, we hypothesized that introduction of vitamin E into UHMWPE before high temperature melting could improve the oxidative stability of these UHMWPEs with low wear and high toughness. Vitamin E was blended with UHMWPE powder at concentrations of 0.1 and 0.2 wt% and consolidated, followed by melting at 300 and 320 degrees C for 5 h, and subsequent irradiation with electron beam to 150 kGy. These vitamin E/UHMWPE blends showed improved tensile and impact toughness and good wear resistance in comparison with the radiation cross-linked vitamin E/UHMWPE blends. Aggressive accelerated aging with or without pro-oxidant lipids showed that vitamin E-blended, high temperature melted and subsequently irradiated UHMWPE had good oxidation resistance. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Fu, Jun; Doshi, Brinda N.; Oral, Ebru; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Harris Orthoped Lab, Boston, MA 02114 USA. [Fu, Jun; Oral, Ebru; Muratoglu, Orhun K.] Harvard Univ, Sch Med, Boston, MA USA. RP Oral, E (reprint author), Massachusetts Gen Hosp, Harris Orthoped Lab, 55 Fruit St,GRJ 1206, Boston, MA 02114 USA. EM eoral@partners.org RI Fu, Jun/C-1648-2012 OI Fu, Jun/0000-0002-8723-1439 FU Harris Orthopedic Laboratory FX This study was funded by the Harris Orthopedic Laboratory. NR 37 TC 13 Z9 13 U1 2 U2 31 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0032-3861 J9 POLYMER JI Polymer PD JAN 8 PY 2013 VL 54 IS 1 BP 199 EP 209 DI 10.1016/j.polymer.2012.11.017 PG 11 WC Polymer Science SC Polymer Science GA 190QT UT WOS:000322356000024 ER PT J AU Rask-Madsen, C King, GL AF Rask-Madsen, Christian King, George L. TI Vascular Complications of Diabetes: Mechanisms of Injury and Protective Factors SO CELL METABOLISM LA English DT Review ID PROTEIN-KINASE-C; ENDOPLASMIC-RETICULUM-STRESS; ENDOTHELIAL GROWTH-FACTOR; NITRIC-OXIDE SYNTHASE; E-NULL MICE; ADVANCED ATHEROSCLEROTIC LESIONS; PKC BETA INHIBITOR; DEFICIENT MICE; IN-VIVO; OXIDATIVE-STRESS AB In patients with diabetes, atherosclerosis is the main reason for impaired life expectancy, and diabetic nephropathy and retinopathy are the largest contributors to end-stage renal disease and blindness, respectively. An improved therapeutic approach to combat diabetic vascular complications might include blocking mechanisms of injury as well as promoting protective or regenerating factors, for example by enhancing the action of insulin-regulated genes in endothelial cells, promoting gene programs leading to induction of antioxidant or anti-inflammatory factors, or improving the sensitivity to vascular cell survival factors. Such strategies could help prevent complications despite suboptimal metabolic control. C1 [Rask-Madsen, Christian; King, George L.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP King, GL (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM george.king@joslin.harvard.edu FU NIH [K08 EY018677, R01 DK053105, EY016150]; NIDDK Diabetes Research Center [P30DK036836] FX C.R.-M. is supported by NIH grant K08 EY018677 and G.L.K. by NIH grant R01 DK053105 and EY016150. This work was also supported by NIDDK Diabetes Research Center grant P30DK036836. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. NR 94 TC 99 Z9 106 U1 1 U2 41 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD JAN 8 PY 2013 VL 17 IS 1 BP 20 EP 33 DI 10.1016/j.cmet.2012.11.012 PG 14 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 076ZX UT WOS:000313998800006 PM 23312281 ER PT J AU Kudo, M Soltani, SMAK Sakuma, SA McKleroy, W Lee, TH Woodruff, PG Lee, JW Huang, K Chen, C Arjomandi, M Huang, XZ Atabai, K AF Kudo, Makoto Soltani, S. M. Amin Khalifeh Sakuma, Stephen A. McKleroy, William Lee, Ting-Hein Woodruff, Prescott G. Lee, Jae Woo Huang, Katherine Chen, Chun Arjomandi, Mehrdad Huang, Xiaozhu Atabai, Kamran TI Mfge8 suppresses airway hyperresponsiveness in asthma by regulating smooth muscle contraction SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE calcium sensitivity; lactadherin ID ACUTE LUNG INJURY; APOPTOTIC CELLS; T-CELLS; ALLERGIC-ASTHMA; INTEGRIN; MICE; DISEASE; HYPERREACTIVITY; INTERLEUKIN-13; SENSITIZATION AB Airway obstruction is a hallmark of allergic asthma and is caused primarily by airway smooth muscle (ASM) hypercontractility. Airway inflammation leads to the release of cytokines that enhance ASM contraction by increasing ras homolog gene family, member A (RhoA) activity. The protective mechanisms that prevent or attenuate the increase in RhoA activity have not been well studied. Here, we report that mice lacking the gene that encodes the protein Milk Fat Globule-EGF factor 8 (Mfge8(-/-)) develop exaggerated airway hyperresponsiveness in experimental models of asthma. Mfge8(-/-) ASM had enhanced contraction after treatment with IL-13, IL-17A, or TNF-alpha. Recombinant Mfge8 reduced contraction in murine and human ASM treated with IL-13. Mfge8 inhibited IL-13-induced NF-kappa B activation and induction of RhoA. Mfge8 also inhibited rapid activation of RhoA, an effect that was eliminated by an inactivating point mutation in the RGD integrin-binding site in recombinant Mfge8. Human subjects with asthma had decreased Mfge8 expression in airway biopsies compared with healthy controls. These data indicate that Mfge8 binding to integrin receptors on ASM opposes the effect of allergic inflammation on RhoA activity and identify a pathway for specific inhibition of ASM hypercontractility in asthma. C1 [Kudo, Makoto; Huang, Katherine; Chen, Chun; Arjomandi, Mehrdad; Huang, Xiaozhu; Atabai, Kamran] Univ Calif San Francisco, Lung Biol Ctr, San Francisco, CA 94143 USA. [Kudo, Makoto] Yokohama City Univ, Grad Sch Med, Dept Internal Med & Clin Immunol, Yokohama, Kanagawa 2360004, Japan. [Soltani, S. M. Amin Khalifeh; Sakuma, Stephen A.; McKleroy, William; Lee, Ting-Hein; Atabai, Kamran] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Soltani, S. M. Amin Khalifeh; Sakuma, Stephen A.; McKleroy, William; Lee, Ting-Hein; Woodruff, Prescott G.; Huang, Katherine; Chen, Chun; Huang, Xiaozhu; Atabai, Kamran] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Lee, Jae Woo] Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. [Arjomandi, Mehrdad] San Francisco VA Med Ctr, Pulm Res Grp, San Francisco, CA 94121 USA. RP Atabai, K (reprint author), Univ Calif San Francisco, Lung Biol Ctr, San Francisco, CA 94143 USA. EM kamran.atabai@ucsf.edu FU National Institutes of Health (NIH) [HL083985, AI081988]; Sandler Program in Basic Sciences; NIH [K23 HL083099]; NIH/National Center for Research Resources, Office of the Director [KL2 RR024130] FX This work was supported by National Institutes of Health (NIH) Grants HL083985 and AI081988 (to K. A.), a grant from the Sandler Program in Basic Sciences (to K. A.), NIH Grant K23 HL083099 (to M. A.), and NIH/National Center for Research Resources, Office of the Director Grant KL2 RR024130 to the UCSF Clinical and Translational Science Institute. NR 47 TC 14 Z9 14 U1 0 U2 17 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 8 PY 2013 VL 110 IS 2 BP 660 EP 665 DI 10.1073/pnas.1216673110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 075SK UT WOS:000313906600058 PM 23269839 ER PT J AU Calebiro, D Rieken, F Wagner, J Sungkaworn, T Zabel, U Borzi, A Cocucci, E Zurn, A Lohse, MJ AF Calebiro, Davide Rieken, Finn Wagner, Julia Sungkaworn, Titiwat Zabel, Ulrike Borzi, Alfio Cocucci, Emanuele Zuern, Alexander Lohse, Martin J. TI Single-molecule analysis of fluorescently labeled G-protein-coupled receptors reveals complexes with distinct dynamics and organization SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE live cell imaging; protein-protein interactions ID RESONANCE ENERGY-TRANSFER; FUNCTIONAL GABA(B) RECEPTOR; BETA(2)-ADRENERGIC RECEPTOR; GPCR OLIGOMERIZATION; LIVING CELLS; BRET ANALYSIS; HETERODIMERIZATION; DIMERIZATION; TRAFFICKING; HOMODIMERIZATION AB G-protein-coupled receptors (GPCRs) constitute the largest family of receptors and major pharmacological targets. Whereas many GPCRs have been shown to form di-/oligomers, the size and stability of such complexes under physiological conditions are largely unknown. Here, we used direct receptor labeling with SNAP-tags and total internal reflection fluorescence microscopy to dynamically monitor single receptors on intact cells and thus compare the spatial arrangement, mobility, and supramolecular organization of three prototypical GPCRs: the beta(1)-adrenergic receptor (beta(1)AR), the beta(2)-adrenergic receptor (beta(2)AR), and the.-aminobutyric acid (GABA(B)) receptor. These GPCRs showed very different degrees of di-/oligomerization, lowest for beta(1)ARs (monomers/dimers) and highest for GABA(B) receptors (prevalently dimers/tetramers of heterodimers). The size of receptor complexes increased with receptor density as a result of transient receptor-receptor interactions. Whereas beta(1)-/beta(2)ARs were apparently freely diffusing on the cell surface, GABA(B) receptors were prevalently organized into ordered arrays, via interaction with the actin cytoskeleton. Agonist stimulation did not alter receptor di-/oligomerization, but increased the mobility of GABA(B) receptor complexes. These data provide a spatiotemporal characterization of beta(1)-/beta(2)ARs and GABA(B) receptors at single-molecule resolution. The results suggest that GPCRs are present on the cell surface in a dynamic equilibrium, with constant formation and dissociation of new receptor complexes that can be targeted, in a ligand-regulated manner, to different cell-surface microdomains. C1 [Calebiro, Davide; Rieken, Finn; Wagner, Julia; Sungkaworn, Titiwat; Zabel, Ulrike; Zuern, Alexander; Lohse, Martin J.] Univ Wurzburg, Inst Pharmacol & Toxicol, D-97078 Wurzburg, Germany. [Calebiro, Davide; Rieken, Finn; Wagner, Julia; Sungkaworn, Titiwat; Zabel, Ulrike; Lohse, Martin J.] Univ Wurzburg, Rudolf Virchow Ctr, Deutsch Forsch Gemeinschaft Res Ctr Expt Biomed, D-97078 Wurzburg, Germany. [Sungkaworn, Titiwat] Mahidol Univ, Fac Sci, Dept Physiol, Bangkok 10400, Thailand. [Borzi, Alfio] Univ Wurzburg, Inst Math, D-97074 Wurzburg, Germany. [Cocucci, Emanuele] Boston Childrens Hosp, Program Cellular & Mol Med, Immune Dis Inst, Boston, MA 02115 USA. [Cocucci, Emanuele] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Calebiro, D (reprint author), Univ Wurzburg, Inst Pharmacol & Toxicol, D-97078 Wurzburg, Germany. EM davide.calebiro@toxi.uni-wuerzburg.de; lohse@toxi.uni-wuerzburg.de RI Lohse, Martin/A-7160-2012; OI Lohse, Martin/0000-0002-0599-3510; calebiro, davide/0000-0002-3811-1553 FU European Research Council; Deutsche Forschungsgemeinschaft [SFB487]; Royal Golden Jubilee Ph.D. Program FX We thank Bianca Klupfel, Monika Frank, and Christian Dees for excellent technical support. This work was supported by grants from the European Research Council (Advanced Grant Towards the Quantal Nature of Receptor/cAMP Signals) and the Deutsche Forschungsgemeinschaft (SFB487). T. S. was partially supported by the Royal Golden Jubilee Ph.D. Program. NR 41 TC 111 Z9 113 U1 8 U2 100 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 8 PY 2013 VL 110 IS 2 BP 743 EP 748 DI 10.1073/pnas.1205798110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 075SK UT WOS:000313906600072 PM 23267088 ER PT J AU Kim, PG Albacker, CE Lu, YF Jang, IH Lim, Y Heffner, GC Arora, N Bowman, TV Lin, MI Lensch, MW De Los Angeles, A Zon, LI Loewer, S Daley, GQ AF Kim, Peter Geon Albacker, Colleen E. Lu, Yi-fen Jang, Il-ho Lim, Yoowon Heffner, Garrett C. Arora, Natasha Bowman, Teresa V. Lin, Michelle I. Lensch, M. William De Los Angeles, Alejandro Zon, Leonard I. Loewer, Sabine Daley, George Q. TI Signaling axis involving Hedgehog, Notch, and Scl promotes the embryonic endothelial-to-hematopoietic transition SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE dorsal aorta; runx1; hematopoietic stem cell; AGM; Tie2 ID STEM-CELL DEVELOPMENT; MURINE YOLK-SAC; MOUSE EMBRYO; DEFINITIVE HEMATOPOIESIS; HAEMOGENIC ENDOTHELIUM; ZEBRAFISH EMBRYOS; LINEAGE ANALYSIS; BLOOD FORMATION; DORSAL AORTA; VE-CADHERIN AB During development, the hematopoietic lineage transits through hemogenic endothelium, but the signaling pathways effecting this transition are incompletely characterized. Although the Hedgehog (Hh) pathway is hypothesized to play a role in patterning blood formation, early embryonic lethality of mice lacking Hh signaling precludes such analysis. To determine a role for Hh signaling in patterning of hemogenic endothelium, we assessed the effect of altered Hh signaling in differentiating mouse ES cells, cultured mouse embryos, and developing zebrafish embryos. In differentiating mouse ES cells and mouse yolk sac cultures, addition of Indian Hh ligand increased hematopoietic progenitors, whereas chemical inhibition of Hh signaling reduced hematopoietic progenitors without affecting primitive streak mesoderm formation. In the setting of Hh inhibition, induction of either Notch signaling or overexpression of Stem cell leukemia (Scl)/T-cell acute lymphocytic leukemia protein 1 rescued hemogenic vascular-endothelial cadherin(+) cells and hematopoietic progenitor formation. Together, our results reveal that Scl overexpression is sufficient to rescue the developmental defects caused by blocking the Hh and Notch pathways, and inform our understanding of the embryonic endothelial-to-hematopoietic transition. C1 [Kim, Peter Geon; Lu, Yi-fen; Jang, Il-ho; Lim, Yoowon; Heffner, Garrett C.; Arora, Natasha; Lensch, M. William; De Los Angeles, Alejandro; Loewer, Sabine; Daley, George Q.] Boston Childrens Hosp, Stem Cell Transplantat Program, Div Pediat Hematol Oncol, Manton Ctr Orphan Dis Res,Howard Hughes Med Inst, Boston, MA 02115 USA. [Kim, Peter Geon; Lu, Yi-fen; Jang, Il-ho; Lim, Yoowon; Heffner, Garrett C.; Arora, Natasha; Lensch, M. William; De Los Angeles, Alejandro; Loewer, Sabine; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kim, Peter Geon; Lu, Yi-fen; Jang, Il-ho; Lim, Yoowon; Heffner, Garrett C.; Arora, Natasha; Lensch, M. William; De Los Angeles, Alejandro; Loewer, Sabine; Daley, George Q.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Kim, Peter Geon; Lu, Yi-fen; Jang, Il-ho; Lim, Yoowon; Heffner, Garrett C.; Arora, Natasha; Lensch, M. William; De Los Angeles, Alejandro; Loewer, Sabine; Daley, George Q.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Kim, Peter Geon; Lu, Yi-fen; Jang, Il-ho; Lim, Yoowon; Heffner, Garrett C.; Arora, Natasha; Lensch, M. William; De Los Angeles, Alejandro; Loewer, Sabine; Daley, George Q.] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA. [Albacker, Colleen E.; Bowman, Teresa V.; Lin, Michelle I.; Zon, Leonard I.] Harvard Univ, Sch Med, Stem Cell Program, Boston, MA 02115 USA. [Albacker, Colleen E.; Bowman, Teresa V.; Lin, Michelle I.; Zon, Leonard I.] Harvard Univ, Sch Med, Boston Childrens Hosp, Howard Hughes Med Inst,Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Loewer, S (reprint author), Boston Childrens Hosp, Stem Cell Transplantat Program, Div Pediat Hematol Oncol, Manton Ctr Orphan Dis Res,Howard Hughes Med Inst, Boston, MA 02115 USA. EM sabine.loewer@mdc-berlin.de; george.daley@childrens.harvard.edu FU US National Institutes of Health (NIH Heart, Lung and Blood Institute Progenitor Cell Biology Consortium); Roche Foundation for Anemia Research; Doris Duke Medical Foundation FX The inducible Scl mESC line is a gift from Michael Kyba. G. Q. D. is an investigator of the Howard Hughes Medical Institute and the Manton Center for Orphan Disease Research. G. Q. D. is supported by grants from the US National Institutes of Health (NIH Heart, Lung and Blood Institute Progenitor Cell Biology Consortium), the Roche Foundation for Anemia Research, and the Doris Duke Medical Foundation. NR 50 TC 37 Z9 39 U1 2 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 8 PY 2013 VL 110 IS 2 BP E141 EP E150 DI 10.1073/pnas.1214361110 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 075SK UT WOS:000313906600008 PM 23236128 ER PT J AU Ganguli, I Collins, JE Reichmann, WM Losina, E Katz, JN Arbelaez, C Donnell-Fink, LA Walensky, RP AF Ganguli, Ishani Collins, Jamie E. Reichmann, William M. Losina, Elena Katz, Jeffrey N. Arbelaez, Christian Donnell-Fink, Laurel A. Walensky, Rochelle P. TI Missed Opportunities: Refusal to Confirm Reactive Rapid HIV Tests in the Emergency Department SO PLOS ONE LA English DT Article ID UNITED-STATES; PATIENT PERCEPTIONS; SCREENING-PROGRAM; CARE; INFECTION; ACCEPTANCE; WOMEN AB Background: HIV infection remains a major US public health concern. While HIV-infected individuals now benefit from earlier diagnosis and improved treatment options, progress is tempered by large numbers of newly diagnosed patients who are lost to follow-up prior to disease confirmation and linkage to care. Methodology: In the randomized, controlled USHER trial, we offered rapid HIV tests to patients presenting to a Boston, MA emergency department. Separate written informed consent was required for confirmatory testing. In a secondary analysis, we compared participants with reactive results who did and did not complete confirmatory testing to identify factors associated with refusal to complete the confirmation protocol. Principal Findings: Thirteen of 62 (21.0%, 95% CI (11.7%, 33.2%)) participants with reactive rapid HIV tests refused confirmation; women, younger participants, African Americans, and those with fewer HIV risks, with lower income, and without primary care doctors were more likely to refuse. We projected that up to four true HIV cases were lost at the confirmation stage. Conclusions: These findings underscore the need to better understand the factors associated with refusal to confirm reactive HIV testing and to identify interventions that will facilitate confirmatory testing and linkage to care among these populations. C1 [Ganguli, Ishani; Walensky, Rochelle P.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Collins, Jamie E.; Reichmann, William M.; Losina, Elena; Katz, Jeffrey N.; Donnell-Fink, Laurel A.] Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. [Collins, Jamie E.; Reichmann, William M.; Losina, Elena] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA USA. [Losina, Elena; Katz, Jeffrey N.; Walensky, Rochelle P.] Harvard Univ, Sch Med, Boston, MA USA. [Losina, Elena; Walensky, Rochelle P.] Harvard Univ, Ctr AIDS Res, Boston, MA USA. [Katz, Jeffrey N.] Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Katz, Jeffrey N.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Arbelaez, Christian] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Walensky, Rochelle P.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Walensky, Rochelle P.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02115 USA. RP Walensky, RP (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. EM rwalensky@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X FU National Institute of Mental Health [R01 MH073445]; Doris Duke Charitable Foundation FX This work was supported in part by the National Institute of Mental Health (http://www.nimh.nih.gov/) R01 MH073445 and The Doris Duke Charitable Foundation, Clinical Scientist Development Award (http://www.ddcf.org/mrp-csda). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 1 Z9 1 U1 2 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 8 PY 2013 VL 8 IS 1 AR e53408 DI 10.1371/journal.pone.0053408 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 069IY UT WOS:000313429800048 PM 23308216 ER PT J AU Gear, R Becerra, L Upadhyay, J Bishop, J Wallin, D Pendse, G Levine, J Borsook, D AF Gear, Robert Becerra, Lino Upadhyay, Jaymin Bishop, James Wallin, Diana Pendse, Gautam Levine, Jon Borsook, David TI Pain Facilitation Brain Regions Activated by Nalbuphine Are Revealed by Pharmacological fMRI SO PLOS ONE LA English DT Article ID PREFRONTAL CORTICAL PROJECTIONS; ANTERIOR CINGULATE CORTEX; NOXIOUS THERMAL STIMULI; LONGITUDINAL COLUMNS; PERIAQUEDUCTAL GRAY; CEREBRAL ACTIVATION; HEALTHY-VOLUNTEERS; ANALGESIA; HUMANS; NALOXONE AB Nalbuphine, an agonist-antagonist kappa-opioid, produces brief analgesia followed by enhanced pain/hyperalgesia in male postsurgical patients. However, it produces profound analgesia without pain enhancement when co-administration with low dose naloxone. To examine the effect of nalbuphine or nalbuphine plus naloxone on activity in brain regions that may explain these differences, we employed pharmacological magnetic resonance imaging (phMRI) in a double blind cross-over study with 13 healthy male volunteers. In separate imaging sessions subjects were administered nalbuphine (5 mg/70 kg) preceded by either saline (Sal-Nalb) or naloxone 0.4 mg (Nalox-Nalb). Blood oxygen level-dependent (BOLD) activation maps followed by contrast and connectivity analyses revealed marked differences. Sal-Nalb produced significantly increased activity in 60 brain regions and decreased activity in 9; in contrast, Nalox-Nalb activated only 14 regions and deactivated only 3. Nalbuphine, like morphine in a previous study, attenuated activity in the inferior orbital cortex, and, like noxious stimulation, increased activity in temporal cortex, insula, pulvinar, caudate, and pons. Co-administration/pretreatment of naloxone selectively blocked activity in pulvinar, pons and posterior insula. Nalbuphine induced functional connectivity between caudate and regions in the frontal, occipital, temporal, insular, middle cingulate cortices, and putamen; naloxone co-admistration reduced all connectivity to non-significant levels, and, like phMRI measures of morphine, increased activation in other areas (e.g., putamen). Naloxone pretreatment to nalbuphine produced changes in brain activity possess characteristics of both analgesia and algesia; naloxone selectively blocks activity in areas associated with algesia. Given these findings, we suggest that nalbuphine interacts with a pain salience system, which can modulate perceived pain intensity. C1 [Gear, Robert; Levine, Jon] Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, San Francisco, CA 94143 USA. [Becerra, Lino; Upadhyay, Jaymin; Bishop, James; Wallin, Diana; Pendse, Gautam; Borsook, David] Harvard Univ, Sch Med, Ctr Pain & Brain, Boston, MA USA. [Becerra, Lino; Upadhyay, Jaymin; Bishop, James; Wallin, Diana; Pendse, Gautam; Borsook, David] McLean Hosp, Brain Imaging Ctr, Belmont, MA 02178 USA. [Becerra, Lino; Borsook, David] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Becerra, Lino; Borsook, David] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Levine, Jon] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Levine, J (reprint author), Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, San Francisco, CA 94143 USA. EM jon.levine@ucsf.edu OI Wallin, Diana/0000-0003-4244-0314 FU National Institutes of Health [DE018526]; NINDS [K24]; Louis Herlands Fund for Pain Research FX This work was supported by National Institutes of Health grant DE018526 (JL); NINDS K24 (DB); and Louis Herlands Fund for Pain Research (DB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 7 Z9 7 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 8 PY 2013 VL 8 IS 1 AR e50169 DI 10.1371/journal.pone.0050169 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 069IY UT WOS:000313429800004 PM 23341872 ER PT J AU Pinne, M Haake, DA AF Pinne, Marija Haake, David A. TI LipL32 Is a Subsurface Lipoprotein of Leptospira interrogans: Presentation of New Data and Reevaluation of Previous Studies SO PLOS ONE LA English DT Article ID OUTER-MEMBRANE PROTEIN; SURFACE-EXPOSED LIPOPROTEIN; PATHOGENIC LEPTOSPIRA; MONOCLONAL-ANTIBODIES; MOLECULAR-CLONING; SEQUENCE-ANALYSIS; INFECTION; FIBRONECTIN; EPIDEMIC; ANTIGEN AB The agents of leptospirosis, a zoonosis with worldwide distribution, are pathogenic spirochetes belonging to the genus Leptospira. The leptospiral life cycle involves transmission via fresh water and colonization of the renal tubules of their reservoir hosts. Infection of accidental hosts, including humans, may result in life-threatening sequelae. Bacterial outer membrane proteins (OMPs), particularly those with surface-exposed regions, play crucial roles in pathogen virulence mechanisms and adaptation to environmental conditions, including those found in the mammalian host. Therefore, elucidation and characterization of the surface-exposed OMPs of Leptospira spp. is of great interest in the leptospirosis field. A thorough, multi-pronged approach for assessing surface exposure of leptospiral OMPs is essential. Herein, we present evidence for a sub-surface location for most or all of the major leptospiral lipoprotein, LipL32, based on surface immunofluorescence utilizing three different types of antibodies and four different permeabilization methods, as well as surface proteolysis of intact and lysed leptospires. We reevaluate prior evidence presented in support of LipL32 surface-exposure and present a novel perspective on a protein whose location has been misleading researchers, due in large part to its extraordinary abundance in leptospiral cells. C1 [Pinne, Marija] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. [Haake, David A.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA. [Pinne, Marija; Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Haake, David A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Haake, David A.] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA USA. RP Pinne, M (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. EM mpinne@ucla.edu FU VA Medical Research Funds; National Institute of Allergy and Infectious Diseases [AI-034431] FX This study was supported by VA Medical Research Funds (to D. A. H.) and grant AI-034431 (to D. A. H.) from the National Institute of Allergy and Infectious Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 21 Z9 22 U1 0 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 8 PY 2013 VL 8 IS 1 AR e51025 DI 10.1371/journal.pone.0051025 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 069IY UT WOS:000313429800006 PM 23323152 ER PT J AU Sartelli, M Viale, P Catena, F Ansaloni, L Moore, E Malangoni, M Moore, FA Velmahos, G Coimbra, R Ivatury, R Peitzman, A Koike, K Leppaniemi, A Biffl, W Burlew, CC Balogh, ZJ Boffard, K Bendinelli, C Gupta, S Kluger, Y Agresta, F Di Saverio, S Wani, I Escalona, A Ordonez, C Fraga, GP Pereira, GA Bala, M Cui, YF Marwah, S Sakakushev, B Kong, V Naidoo, N Ahmed, A Abbas, A Guercioni, G Vettoretto, N Diaz-Nieto, R Gerych, I Trana, C Faro, MP Yuan, KC Kok, KYY Mefire, AC Lee, JG Hong, SK Ghnnam, W Siribumrungwong, B Sato, N Murata, K Irahara, T Coccolini, F Lohse, HAS Verni, A Shoko, T AF Sartelli, Massimo Viale, Pierluigi Catena, Fausto Ansaloni, Luca Moore, Ernest Malangoni, Mark Moore, Frederick A. Velmahos, George Coimbra, Raul Ivatury, Rao Peitzman, Andrew Koike, Kaoru Leppaniemi, Ari Biffl, Walter Burlew, Clay Cothren Balogh, Zsolt J. Boffard, Ken Bendinelli, Cino Gupta, Sanjay Kluger, Yoram Agresta, Ferdinando Di Saverio, Salomone Wani, Imtiaz Escalona, Alex Ordonez, Carlos Fraga, Gustavo P. Pereira Junior, Gerson Alves Bala, Miklosh Cui, Yunfeng Marwah, Sanjay Sakakushev, Boris Kong, Victor Naidoo, Noel Ahmed, Adamu Abbas, Ashraf Guercioni, Gianluca Vettoretto, Nereo Diaz-Nieto, Rafael Gerych, Ihor Trana, Cristian Faro, Mario Paulo Yuan, Kuo-Ching Kok, Kenneth Yuh Yen Mefire, Alain Chichom Lee, Jae Gil Hong, Suk-Kyung Ghnnam, Wagih Siribumrungwong, Boonying Sato, Norio Murata, Kiyoshi Irahara, Takayuki Coccolini, Federico Segovia Lohse, Helmut A. Verni, Alfredo Shoko, Tomohisa TI 2013 WSES guidelines for management of intra-abdominal infections SO WORLD JOURNAL OF EMERGENCY SURGERY LA English DT Review ID PERFORATED PEPTIC-ULCER; DAMAGE CONTROL LAPAROTOMY; RANDOMIZED CONTROLLED-TRIALS; TYPHOID ILEAL PERFORATION; ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY; UNCOMPLICATED ACUTE APPENDICITIS; ANTIMICROBIAL RESISTANCE TRENDS; LAPAROSCOPIC PERITONEAL-LAVAGE; ACUTE CALCULOUS CHOLECYSTITIS; IMMEDIATE DEFINITIVE SURGERY AB Despite advances in diagnosis, surgery, and antimicrobial therapy, mortality rates associated with complicated intra-abdominal infections remain exceedingly high. The 2013 update of the World Society of Emergency Surgery (WSES) guidelines for the management of intra-abdominal infections contains evidence-based recommendations for management of patients with intra-abdominal infections. C1 [Sartelli, Massimo] Macerata Hosp, Dept Surg, Macerata, Italy. [Viale, Pierluigi] St Orsola Malpighi Univ Hosp, Dept Internal Med Geriatr & Nephrol Dis, Clin Infect Dis, Bologna, Italy. [Catena, Fausto] Maggiore Parma Hosp, Parma, Italy. [Ansaloni, Luca; Coccolini, Federico] Osped Riuniti Bergamo, Dept Gen Surg, I-24100 Bergamo, Italy. [Moore, Ernest; Biffl, Walter; Burlew, Clay Cothren] Denver Hlth Med Ctr, Dept Surg, Denver, CO USA. [Malangoni, Mark] Amer Board Surg, Philadelphia, PA USA. [Moore, Frederick A.] Univ Texas Hlth Sci Ctr, Houston, TX USA. [Velmahos, George] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA USA. [Coimbra, Raul] UC San Diego Hlth Syst, Dept Surg, San Diego, CA USA. [Ivatury, Rao] Virginia Commonwealth Univ, Med Ctr, Dept Surg, Richmond, VA USA. [Peitzman, Andrew; Sato, Norio] Univ Pittsburgh, Med Ctr, Div Gen Surg, Pittsburgh, PA USA. [Koike, Kaoru] Kyoto Univ, Grad Sch Med, Dept Primary Care & Emergency Med, Kyoto, Japan. [Leppaniemi, Ari] Univ Hosp Meilahti, Dept Abdominal Surg, Helsinki, Finland. [Balogh, Zsolt J.; Bendinelli, Cino] Univ Newcastle, Dept Surg, Newcastle, NSW 2300, Australia. [Boffard, Ken] Univ Witwatersrand, Dept Surg, Charlotte Maxeke Johannesburg Hosp, Johannesburg, South Africa. [Gupta, Sanjay] Govt Med Coll & Hosp, Dept Surg, Chandigarh, India. [Kluger, Yoram] Rambam Hlth Care Campus, Dept Gen Surg, Haifa, Israel. [Agresta, Ferdinando] Adria Hosp, Dept Surg, Adria, Italy. [Di Saverio, Salomone] Maggiore Hosp, Dept Surg, Bologna, Italy. [Wani, Imtiaz] Pontificia Univ Catolica Chile, Fac Med, Dept Digest Surg, Santiago, Chile. [Escalona, Alex] Sheri Kashmir Inst Med Sci, Dept Surg, Srinagar, Jammu & Kashmir, India. [Ordonez, Carlos] Univ Valle, Dept Surg, Fdn Valle Lili, Cali, Colombia. [Fraga, Gustavo P.] Univ Estadual Campinas, Hosp Clin, Div Trauma Surg, Campinas, SP, Brazil. [Pereira Junior, Gerson Alves] Dept Surg, Emergency Unit, Ribeirao Preto, Brazil. [Bala, Miklosh] Hadassah Med Ctr, Dept Gen Surg, IL-91120 Jerusalem, Israel. [Cui, Yunfeng] Tianjin Med Univ, Nankai Clin Sch Med, Tianjin Nankai Hosp, Dept Surg, Tianjin, Peoples R China. [Marwah, Sanjay] Pt BDS Postgrad Inst Med Sci, Dept Surg, Rohtak, Haryana, India. [Sakakushev, Boris] Univ Hosp UMBAL St George Plovdiv, Clin Gen Surg 1, Plovdiv, Bulgaria. [Kong, Victor] Edendale Hosp, Dept Surg, Pietermaritzburg, South Africa. [Naidoo, Noel] Port Shepstone Hosp, Dept Surg, Kwa Zulu, South Africa. [Ahmed, Adamu] Ahmadu Bello Univ, Teaching Hosp Zaria, Dept Surg, Kaduna, Nigeria. [Abbas, Ashraf] Mansoura Univ Hosp, Dept Surg, Mansoura, Egypt. [Guercioni, Gianluca] Mazzoni Hosp, Dept Surg, Ascoli Piceno, Italy. [Vettoretto, Nereo] Mellini Hosp, Dept Surg, Chiari, BS, Italy. [Diaz-Nieto, Rafael] Univ Hosp, Dept Gen & Digest Surg, Malaga, Spain. [Gerych, Ihor] Lviv Emergency Hosp, Dept Gen Surg, Lvov, Ukraine. [Trana, Cristian] Univ Ancona, Dept Surg, Ancona, Italy. [Faro, Mario Paulo] Fundacao ABC, Fac Med, Div Gen & Emergency Surg, Sao Paulo, Santo Andre, Brazil. [Yuan, Kuo-Ching] Chang Gung Mem Hosp, Dept Surg, Tao Yuan, Taiwan. [Kok, Kenneth Yuh Yen] Ripas Hosp, Dept Surg, Bandar Seri Begawan, Brunei. [Mefire, Alain Chichom] Reg Hosp Limbe & Buea, Limbe, Cameroon. [Lee, Jae Gil] Yonsei Univ, Coll Med, Dept Surg, Severance Hosp, Seoul, South Korea. [Hong, Suk-Kyung] Univ Ulsan, Dept Surg, Div Trauma & Surg Crit Care, Seoul, South Korea. [Ghnnam, Wagih] Khamis Mushayt Gen Hosp, Dept Surg, Khamis Mushayt, Saudi Arabia. [Siribumrungwong, Boonying] Thammasat Univ Hosp, Dept Surg, Pathum Thani, Thailand. [Murata, Kiyoshi] Tokyo Med & Dent Univ, Dept Acute & Crit Care Med, Tokyo, Japan. [Irahara, Takayuki] Tama Nagayama Hosp, Nippon Med Sch, Emergency & Crit Care Ctr, Dept Emergency & Crit Care Med, Tokyo, Japan. [Segovia Lohse, Helmut A.] Hosp Clin, Catedra Clin Quirurg 2, San Lorenzo, Paraguay. [Verni, Alfredo] Cutral Co Clin, Dept Surg, Neuquen, Argentina. [Shoko, Tomohisa] Matsudo City Hosp, Shock Trauma & Emergency Med Ctr, Chiba, Japan. RP Sartelli, M (reprint author), Macerata Hosp, Dept Surg, Macerata, Italy. EM m.sartelli@virgilio.it RI Kok, Kenneth/F-3264-2013; Balogh, Zsolt/A-2002-2010; ghnnam, wagih/I-5212-2013; OI Di Saverio, Salomone/0000-0001-5685-5022; Balogh, Zsolt/0000-0002-0277-4822; ghnnam, wagih/0000-0003-3599-9929; Ansaloni, Luca/0000-0001-6427-0307; Chichom-Mefire, Alain/0000-0001-7230-567X; Sakakushev, Boris/0000-0001-8399-0115; Agresta, Ferdinando/0000-0002-6114-1881; Boffard, Kenneth/0000-0002-7159-5414 NR 280 TC 73 Z9 84 U1 6 U2 38 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1749-7922 J9 WORLD J EMERG SURG JI World J. Emerg. Surg. PD JAN 8 PY 2013 VL 8 AR 3 DI 10.1186/1749-7922-8-3 PG 29 WC Emergency Medicine; Surgery SC Emergency Medicine; Surgery GA 073BQ UT WOS:000313718700001 PM 23294512 ER PT J AU Rassi, AN Cavender, MA Fonarow, GC Cannon, CP Hernandez, AF Peterson, ED Peacock, WF Laskey, WK Rosas, SE Zhao, X Schwamm, LH Bhatt, DL AF Rassi, Andrew N. Cavender, Matthew A. Fonarow, Gregg C. Cannon, Christopher P. Hernandez, Adrian F. Peterson, Eric D. Peacock, W. Frank Laskey, Warren K. Rosas, Sylvia E. Zhao, Xin Schwamm, Lee H. Bhatt, Deepak L. TI Temporal Trends and Predictors in the Use of Aldosterone Antagonists Post-Acute Myocardial Infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE acute myocardial infarction; aldosterone antagonist; heart failure ID LEFT-VENTRICULAR DYSFUNCTION; HEART-FAILURE EFFICACY; EPLERENONE; GUIDELINES; POTASSIUM; SURVIVAL; EPHESUS AB Objectives This study explored temporal trends in the use of aldosterone antagonist therapy among eligible patients with post-acute myocardial infarction (AMI) and reduced ejection fraction and characteristics associated with use in clinical practice. Background Current guidelines recommend initiation of aldosterone antagonist therapy post-AMI for patients with an ejection fraction <= 40% and heart failure or diabetes before hospital discharge, in the absence of contraindications. Methods Data from the American Heart Association's Get with the Guidelines-Coronary Artery Disease national database were analyzed for 81,570 post-AMI patients from 219 hospitals between 2006 and 2009, of whom 11,255 (13.8%) were eligible for aldosterone antagonist therapy. Results Among eligible patients, 1,023 (9.1%) were prescribed an aldosterone antagonist at discharge. Aldosterone antagonist use varied from 0% to 40% among hospitals. Patient and hospital characteristics independently associated with prescription of aldosterone antagonists were a history of diabetes, heart failure, coronary revascularization, and larger hospital size. Those with a history of kidney dysfunction, tobacco abuse, and higher ejection fraction were less likely to be prescribed an aldosterone antagonist. From 2006 to 2009, the use of aldosterone antagonists increased from 6.0% to 13.4% (p < 0.001). Conclusions Although rates of aldosterone antagonist use are increasing slightly over time, the vast majority of AMI patients eligible for treatment fail to receive it at hospital discharge. The reason for this discrepancy between guideline-based therapy and actual prescribing patterns is unclear and should be further studied. (J Am Coll Cardiol 2013;61:35-40) (C) 2013 by the American College of Cardiology Foundation C1 [Rassi, Andrew N.; Cavender, Matthew A.] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA. [Fonarow, Gregg C.] Ronald Reagan UCLA Med Ctr, Div Cardiol, Los Angeles, CA USA. [Cannon, Christopher P.] Harvard Univ, Sch Med, Boston, MA USA. [Hernandez, Adrian F.; Peterson, Eric D.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Hernandez, Adrian F.; Peterson, Eric D.] Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA. [Peacock, W. Frank] Baylor Coll Med, Houston, TX 77030 USA. [Laskey, Warren K.] Univ New Mexico, Div Cardiol, Albuquerque, NM 87131 USA. [Rosas, Sylvia E.] Philadelphia VA Med Ctr, Renal Electrolyte & Hypertens Div, Philadelphia, PA USA. [Rosas, Sylvia E.] Univ Penn, Philadelphia, PA 19104 USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Div Cardiol, Boston, MA 02132 USA. RP Bhatt, DL (reprint author), Brigham & Womens Hosp, VA Boston Healthcare Syst, Div Cardiol, 1400 VFW Pkwy, Boston, MA 02132 USA. EM dlbhattmd@post.harvard.edu RI Hernandez, Adrian F./A-7818-2016 OI Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616 FU American Heart Association; Accumetrics; AstraZeneca; GlaxoSmithKline; Merck; Takeda; Alere; Brahms; Electrocore; Novartis; Medicines Company; Amarin; Bristol-Myers Squibb; Eisai; Ethicon; Medtronic; sanofi-aventis FX The Get With the Guidelines-Coronary Artery Disease (GWTGCAD) program was provided by the American Heart Association. The GWTGCAD program was supported in part by the American Heart Association Pharmaceutical Roundtable and an unrestricted educational grant from Merck. Dr. Fonarow is an adviser for Novartis. Dr. Cannon receives research grants from Accumetrics, AstraZeneca, GlaxoSmithKline, Merck, and Takeda. Dr. Peacock receives research grants from Alere, Brahms, Electrocore, Novartis, and The Medicines Company; serves on the Speakers' Bureau of Abbott, Alere, and EKR; has ownership interest in Comprehensive Research Associates, Vital Sensors, Emergencies in Medicine; and serves on the scientific advisory board of Abbott, Alere, Lily, and The Medicines Company. Dr. Rosas receives research grants from Abbott Laboratories. Dr. Schwamm serves as Chair of the National Steering Committee for GWTG (unpaid). Dr. Bhatt is on the advisory board of Medscape Cardiology; on the Board of Directors of Boston VA Research Institute and Society of Chest Pain Centers; is Chair of American Heart Association Get With the Guidelines Science Subcommittee; has received honoraria from the American College of Cardiology (Editor of Clinical Trials and Cardiosource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (Chief Medical Editor, Cardiology Today Intervention), and WebMD (CME steering committees); has received research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, sanofi-aventis, and The Medicines Company; and has received unfunded research for FlowCo, PLx Pharma, and Takeda. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 15 TC 20 Z9 20 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 8 PY 2013 VL 61 IS 1 BP 35 EP 40 DI 10.1016/j.jacc.2012.08.1019 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 065PP UT WOS:000313161100006 PM 23137936 ER PT J AU Lee, SJ Boscardin, WJ Stijacic-Cenzer, I Conell-Price, J O'Brien, S Walter, LC AF Lee, Sei J. Boscardin, W. John Stijacic-Cenzer, Irena Conell-Price, Jessamyn O'Brien, Sarah Walter, Louise C. TI Time lag to benefit after screening for breast and colorectal cancer: meta-analysis of survival data from the United States, Sweden, United Kingdom, and Denmark SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Article ID FECAL-OCCULT-BLOOD; RANDOMIZED CONTROLLED-TRIAL; SERVICES TASK-FORCE; FOLLOW-UP; RECOMMENDATION STATEMENT; OLDER-ADULTS; AGE 40; MORTALITY; MAMMOGRAPHY; SIGMOIDOSCOPY AB Objectives To determine a pooled, quantitative estimate of the length of time needed after breast or colorectal cancer screening before a survival benefit is observed. Design Meta-analysis of survival data from population based, randomized controlled trials comparing populations screened and not screened for breast or colorectal cancer. Trials were identified as high quality by reviews from the Cochrane Collaboration and United States Preventive Services Task Force. Setting Trials undertaken in the United States, Denmark, United Kingdom, and Sweden. Population Screened patients older than 40 years. Primary outcome measures Time to death from breast or colorectal cancer in screened and control populations. Interventions Fecal occult blood testing for colorectal cancer screening, mammography for breast cancer screening. Results Our study included five and four eligible trials of breast and colorectal cancer screening, respectively. For breast cancer screening, 3.0 years (95% confidence interval 1.1 to 6.3) passed before one death from breast cancer was prevented for every 5000 women screened. On average across included studies, it took 10.7 years (4.4 to 21.6) before one death from breast cancer was prevented for 1000 women screened. For colorectal cancer screening, 4.8 years (2.0 to 9.7) passed before one death from colorectal cancer was prevented for 5000 patients screened. On average across included studies, it took 10.3 years (6.0 to 16.4) before one death from colorectal cancer was prevented for 1000 patients screened. Conclusions Our results suggest that screening for breast and colorectal cancer is most appropriate for patients with a life expectancy greater than 10 years. Incorporating time lag estimates into screening guidelines would encourage a more explicit consideration of the risks and benefits of screening for breast and colorectal cancer. C1 [Lee, Sei J.; Stijacic-Cenzer, Irena; Walter, Louise C.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Div Geriatr, San Francisco, CA 94121 USA. [Boscardin, W. John] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. [Conell-Price, Jessamyn] Univ Calif San Francisco & Berkeley, Joint Med Program, San Francisco, CA USA. [O'Brien, Sarah] Univ Calif San Francisco, AIDS Educ & Training Evaluat Ctr, San Francisco, CA 94121 USA. RP Lee, SJ (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Div Geriatr, San Francisco, CA 94121 USA. EM sei.lee@ucsf.edu FU Veterans Affairs Medical Center, San Francisco, CA; San Francisco Veterans Affairs Medical Center; Division of Geriatrics, University of California, San Francisco; Hartford Geriatrics Health Outcomes Research Scholars Award; Hellman Family Award for Early Career Faculty at University of California (San Francisco); American Federation of Aging Research and National Institute on Aging [K23AG040779]; National Center for Research Resources, National Institutes of Health [KL2RR024130]; National Institute on Aging [K24AG041180]; National Cancer Institute [R01CA134425] FX This work was supported by the Veterans Affairs Medical Center, San Francisco, CA. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication.; All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: support from the San Francisco Veterans Affairs Medical Center and Division of Geriatrics, University of California, San Francisco for the submitted work; SJL was supported by Hartford Geriatrics Health Outcomes Research Scholars Award, the Hellman Family Award for Early Career Faculty at University of California (San Francisco), K23AG040779 from the American Federation of Aging Research and National Institute on Aging, and KL2RR024130 from the National Center for Research Resources, a component of the National Institutes of Health; LCW was supported by R01CA134425 from the National Cancer Institute and K24AG041180 from the National Institute on Aging administered by the Northern California Institute for Research and Education; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. NR 43 TC 42 Z9 44 U1 1 U2 14 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BMJ-BRIT MED J JI BMJ-British Medical Journal PD JAN 8 PY 2013 VL 346 AR e8441 DI 10.1136/bmj.e8441 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 070ZH UT WOS:000313553800014 PM 23299842 ER PT J AU Tabansky, I Lenarcic, A Draft, RW Loulier, K Keskin, DB Rosains, J Rivera-Feliciano, J Lichtman, JW Livet, J Stern, JNH Sanes, JR Eggan, K AF Tabansky, Inna Lenarcic, Alan Draft, Ryan W. Loulier, Karine Keskin, Derin B. Rosains, Jacqueline Rivera-Feliciano, Jose Lichtman, Jeff W. Livet, Jean Stern, Joel N. H. Sanes, Joshua R. Eggan, Kevin TI Developmental Bias in Cleavage-Stage Mouse Blastomeres SO CURRENT BIOLOGY LA English DT Article ID INNER CELL MASS; BLASTOCYST AXIS; STEM-CELLS; EMBRYO; LINEAGE; ALLOCATION; POLARITY; TROPHECTODERM; EXPRESSION; DIVISION AB Background: The cleavage-stage mouse embryo is composed of superficially equivalent blastomeres that will generate both the embryonic inner cell mass (ICM) and the supportive trophectoderm (TE). However, it remains unsettled whether the contribution of each blastomere to these two lineages can be accounted for by chance. Addressing the question of blastomere cell fate may be of practical importance, because preimplantation genetic diagnosis requires removal of blastomeres from the early human embryo. To determine whether blastomere allocation to the two earliest lineages is random, we developed and utilized a recombination-mediated, noninvasive combinatorial fluorescent labeling method for embryonic lineage tracing. Results: When we induced recombination at cleavage stages, we observed a statistically significant bias in the contribution of the resulting labeled clones to the trophectoderm or the inner cell mass in a subset of embryos. Surprisingly, we did not find a correlation between localization of clones in the embryonic and abembryonic hemispheres of the late blastocyst and their allocation to the TE and ICM, suggesting that TE-ICM bias arises separately from embryonic-abembryonic bias. Rainbow lineage tracing also allowed us to demonstrate that the bias observed in the blastocyst persists into postimplantation stages and therefore has relevance for subsequent development. Conclusions: The Rainbow transgenic mice that we describe here have allowed us to detect lineage-dependent bias in early development. They should also enable assessment of the developmental equivalence of mammalian progenitor cells in a variety of tissues. C1 [Tabansky, Inna; Rivera-Feliciano, Jose; Eggan, Kevin] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Tabansky, Inna; Rivera-Feliciano, Jose; Eggan, Kevin] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Tabansky, Inna; Rivera-Feliciano, Jose; Eggan, Kevin] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Tabansky, Inna; Draft, Ryan W.; Rosains, Jacqueline; Lichtman, Jeff W.; Sanes, Joshua R.; Eggan, Kevin] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Draft, Ryan W.; Lichtman, Jeff W.; Sanes, Joshua R.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Lenarcic, Alan] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Loulier, Karine; Livet, Jean] Univ Paris 06, Inst Vis, INSERM, U968,UMR S 968, F-75012 Paris, France. [Loulier, Karine; Livet, Jean] CNRS, UMR 7210, F-75012 Paris, France. [Keskin, Derin B.; Stern, Joel N. H.] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. [Keskin, Derin B.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Eggan, K (reprint author), Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. EM keggan@scrb.harvard.edu RI livet, jean/C-2766-2012; Loulier, Karine/E-5529-2017; OI Loulier, Karine/0000-0001-6216-2708; Stern, Joel N.H./0000-0002-1259-2256 FU NICHD [HD045732-03]; NIGMS [GM099117] FX We thank the Harvard Genome Modification Facility and A. McMahon for providing transgenic animals and D. Smith, S. Turney, G. Birkhoff, S. Rompani, and S. Fouquet for technical assistance. This work was supported by NICHD grant HD045732-03 and NIGMS P01 grant GM099117 to K.E.; K.E. is also an HHMI Early Career Scientist. NR 38 TC 60 Z9 60 U1 1 U2 26 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JAN 7 PY 2013 VL 23 IS 1 BP 21 EP 31 DI 10.1016/j.cub.2012.10.054 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 068RK UT WOS:000313383700018 PM 23177476 ER PT J AU Mwimanzi, P Markle, TJ Martin, E Ogata, Y Kuang, XMT Tokunaga, M Mahiti, M Pereyra, F Miura, T Walker, BD Brumme, ZL Brockman, MA Ueno, T AF Mwimanzi, Philip Markle, Tristan J. Martin, Eric Ogata, Yoko Kuang, Xiaomei T. Tokunaga, Michiyo Mahiti, Macdonald Pereyra, Florencia Miura, Toshiyuki Walker, Bruce D. Brumme, Zabrina L. Brockman, Mark A. Ueno, Takamasa TI Attenuation of multiple Nef functions in HIV-1 elite controllers SO RETROVIROLOGY LA English DT Article DE HIV-1; Nef; Elite controllers; Human Leukocyte Antigen (HLA) class I; Immune escape; Replication capacity; HLA-B*57 ID IMMUNODEFICIENCY-VIRUS TYPE-1; MEDIATED SELECTIVE PRESSURE; IMMUNE ESCAPE PATHWAYS; CD4 DOWN-REGULATION; CLASS-I MOLECULES; REPLICATION CAPACITY; VIRAL REPLICATION; T-CELLS; INFECTION; PROGRESSION AB Background: Impaired HIV-1 Gag, Pol, and Env function has been described in elite controllers (EC) who spontaneously suppress plasma viremia to < 50 RNA copies/mL; however, activity of the accessory protein Nef remains incompletely characterized. We examined the ability of 91 Nef clones, isolated from plasma of 45 EC and 46 chronic progressors (CP), to down-regulate HLA class I and CD4, up-regulate HLA class II invariant chain (CD74), enhance viral infectivity, and stimulate viral replication in PBMC. Results: In general, EC Nef clones were functional; however, all five activities were significantly lower in EC compared to CP. Nef clones from HLA-B*57-expressing EC exhibited poorer CD4 down-regulation function compared to those from non-B*57 EC, and the number of EC-specific B*57-associated Nef polymorphisms correlated inversely with 4 of 5 Nef functions in these individuals. Conclusion: Results indicate that decreased HIV-1 Nef function, due in part to host immune selection pressures, may be a hallmark of the EC phenotype. C1 [Mwimanzi, Philip; Ogata, Yoko; Tokunaga, Michiyo; Mahiti, Macdonald; Ueno, Takamasa] Kumamoto Univ, Ctr AIDS Res, Kumamoto 8600811, Japan. [Mwimanzi, Philip; Markle, Tristan J.; Martin, Eric; Kuang, Xiaomei T.; Brumme, Zabrina L.; Brockman, Mark A.] Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada. [Pereyra, Florencia; Walker, Bruce D.] MIT, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. [Pereyra, Florencia; Walker, Bruce D.] Harvard Univ, Boston, MA 02115 USA. [Miura, Toshiyuki] Univ Tokyo, Tokyo, Japan. [Brumme, Zabrina L.; Brockman, Mark A.] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada. RP Brockman, MA (reprint author), Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada. EM mark_brockman@sfu.ca; uenotaka@kumamoto-u.ac.jp RI Kumamoto University, CAIDS/G-8446-2013; Publications, Remarkable/I-1756-2013; Ueno, Takamasa/F-5788-2013; OI Ueno, Takamasa/0000-0003-4852-4236; Brockman, Mark/0000-0001-6432-1426 FU Ministry of Education, Science, Sports, and Culture of Japan; Ministry of Health, Labor, and Welfare of Japan; Canadian Institutes for Health Research (CIHR) [MOP-93536]; Bill and Melinda Gates Foundation; Schwartz Foundation; Harvard University Center for AIDS Research; Japan AIDS Foundation; Global Health Research Initiative (GHRI); Canadian International Development Agency; International Development Research Centre; Canadian Association of HIV Research; Abbott Virology; Michael Smith Foundation for Health Research FX We thank Dr. Jonathan Carlson for helpful discussions. This study was supported by a grant-in-aid for scientific research and a Global COE Program (Global Education and Research Center Aiming at the control of AIDS) from the Ministry of Education, Science, Sports, and Culture of Japan, a grant-in-aid for AIDS research from the Ministry of Health, Labor, and Welfare of Japan (to TU), and the Canadian Institutes for Health Research (CIHR) operating grant MOP-93536 (to ZLB and MAB). We acknowledge and thank the International HIV Controllers study, funded by Bill and Melinda Gates Foundation, the Schwartz Foundation and the Harvard University Center for AIDS Research. PM is a postdoctoral fellow who received support from the Japan AIDS Foundation and the Global Health Research Initiative (GHRI), a collaborative research funding partnership of the CIHR, the Canadian International Development Agency, and the International Development Research Centre. EM is supported by a Master's Scholarship from the Canadian Association of HIV Research and Abbott Virology. ZLB is the recipient of a CIHR New Investigator Award and a Scholar Award from the Michael Smith Foundation for Health Research. MAB holds a Canada Research Chair, Tier 2, in Viral Pathogenesis and Immunity. NR 50 TC 35 Z9 35 U1 0 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD JAN 7 PY 2013 VL 10 AR 1 DI 10.1186/1742-4690-10-1 PG 12 WC Virology SC Virology GA 086WE UT WOS:000314718900001 PM 23289738 ER PT J AU Chellappa, V Taylor, KN Pedrick, K Donado, C Netravali, IA Haider, K Cariappa, A Dalomba, NF Pillai, S AF Chellappa, Vasant Taylor, Kendra N. Pedrick, Kathryn Donado, Carlos Netravali, Ilka Arun Haider, Khaleda Cariappa, Annaiah Dalomba, Natasha F. Pillai, Shiv TI M89V Sialic Acid Acetyl Esterase (SIAE) and All Other Non-Synonymous Common Variants of This Gene Are Catalytically Normal SO PLOS ONE LA English DT Article ID DISEASE AB Catalytically defective rare variants of Sialic acid Acetyl Esterase (SIAE) have previously been linked to autoimmunity. Studies presented here confirm that the M89V SIAE protein and all other products of common variant alleles of SIAE are catalytically normal. Although overexpressing transfected non-lymphoid cells secrete small amounts of SIAE that can associate with the cell surface, normal human lymphocytes do not exhibit cell surface SIAE, supporting genetic evidence in mice that indicates that this protein functions in a lymphocyte intrinsic manner. Analyses of the plasma proteome also indicate that SIAE is not secreted in vivo. A re-analysis exclusively of catalytically defective rare variant alleles of SIAE in subjects in which this gene was completely sequenced confirmed an association of SIAE with autoimmunity. A subset of catalytically defective rare variant SIAE alleles has previously been typed in a large genotyping study comparing a diverse group of disease subjects and controls; our re-analysis of this data shows that catalytically defective alleles are enriched in disease subjects. These data suggest that SIAE may be associated with autoimmunity and that further study of catalytically defective rare variant SIAE alleles in terms of autoimmune disease susceptibility is strongly warranted. C1 [Chellappa, Vasant; Taylor, Kendra N.; Pedrick, Kathryn; Donado, Carlos; Netravali, Ilka Arun; Haider, Khaleda; Cariappa, Annaiah; Dalomba, Natasha F.; Pillai, Shiv] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. RP Pillai, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. EM pillai@helix.mgh.harvard.edu FU National Institutes of Health [AI076505, AR058481, AI064930]; Alliance for Lupus Research FX Funds supporting this study were received from grants from the National Institutes of Health - www.nih.gov (grants AI076505, AR058481 and AI064930) and a grant from the Alliance for Lupus Research (www.lupusresearch.org). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 10 TC 8 Z9 8 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 7 PY 2013 VL 8 IS 1 AR e53453 DI 10.1371/journal.pone.0053453 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 069IS UT WOS:000313429100068 PM 23308225 ER PT J AU Xuan, WJ Vatansever, F Huang, LY Wu, QH Xuan, Y Dai, TH Ando, T Xu, T Huang, YY Hamblin, MR AF Xuan, Weijun Vatansever, Fatma Huang, Liyi Wu, Qiuhe Xuan, Yi Dai, Tianhong Ando, Takahiro Xu, Tao Huang, Ying-Ying Hamblin, Michael R. TI Transcranial Low-Level Laser Therapy Improves Neurological Performance in Traumatic Brain Injury in Mice: Effect of Treatment Repetition Regimen SO PLOS ONE LA English DT Article ID BIPHASIC DOSE-RESPONSE; ACUTE ISCHEMIC-STROKE; LIGHT THERAPY; FLUORO-JADE; ADULT BRAIN; NEURONAL DEGENERATION; SUBVENTRICULAR ZONE; STEM-CELLS; DEFICITS; NEUROGENESIS AB Low-level laser (light) therapy (LLLT) has been clinically applied around the world for a spectrum of disorders requiring healing, regeneration and prevention of tissue death. One area that is attracting growing interest in this scope is the use of transcranial LLLT to treat stroke and traumatic brain injury (TBI). We developed a mouse model of severe TBI induced by controlled cortical impact and explored the effect of different treatment schedules. Adult male BALB/c mice were divided into 3 broad groups (a) sham-TBI sham-treatment, (b) real-TBI sham-treatment, and (c) real-TBI active-treatment. Mice received active-treatment (transcranial LLLT by continuous wave 810 nm laser, 25 mW/cm(2), 18 J/cm(2), spot diameter 1 cm) while sham-treatment was immobilization only, delivered either as a single treatment at 4 hours post TBI, as 3 daily treatments commencing at 4 hours post TBI or as 14 daily treatments. Mice were sacrificed at 0, 4, 7, 14 and 28 days post-TBI for histology or histomorphometry, and injected with bromodeoxyuridine (BrdU) at days 21-27 to allow identification of proliferating cells. Mice with severe TBI treated with 1-laser Tx (and to a greater extent 3-laser Tx) had significant improvements in neurological severity score (NSS), and wire-grip and motion test (WGMT). However 14-laser Tx provided no benefit over TBI-sham control. Mice receiving 1-and 3-laser Tx had smaller lesion size at 28-days (although the size increased over 4 weeks in all TBI-groups) and less Fluoro-Jade staining for degenerating neurons (at 14 days) than in TBI control and 14-laser Tx groups. There were more BrdU-positive cells in the lesion in 1-and 3-laser groups suggesting LLLT may increase neurogenesis. Transcranial NIR laser may provide benefit in cases of acute TBI provided the optimum treatment regimen is employed. C1 [Xuan, Weijun; Vatansever, Fatma; Huang, Liyi; Wu, Qiuhe; Xuan, Yi; Dai, Tianhong; Ando, Takahiro; Xu, Tao; Huang, Ying-Ying; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Xuan, Weijun; Vatansever, Fatma; Huang, Liyi; Wu, Qiuhe; Dai, Tianhong; Xu, Tao; Huang, Ying-Ying; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Xuan, Weijun] Tradit Chinese Med Univ Guangxi, Dept Otolaryngol, Nanning, Peoples R China. [Huang, Liyi] Guangxi Med Univ, Affiliated Coll & Hosp 1, Dept Infect Dis, Nanning, Peoples R China. [Wu, Qiuhe] Jinan Ctr Hosp, Dept Burn, Jinan, Peoples R China. [Xuan, Yi] Tufts Univ, Sch Engn, Medford, MA USA. [Ando, Takahiro] Keio Univ, Dept Elect & Elect Engn, Kohoku Ku, Yokohama, Kanagawa 223, Japan. [Xu, Tao] Shanghai Jiao Tong Univ, Lab Anesthesiol, Shanghai 200030, Peoples R China. [Huang, Ying-Ying] Guangxi Med Univ, Aesthet & Plast Ctr, Nanning, Peoples R China. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Huang, Ying-ying/G-3153-2011; OI Huang, Ying-ying/0000-0003-3066-6981; Hamblin, Michael/0000-0001-6431-4605 FU NIH [R01AI050875]; Center for Integration of Medicine and Innovative Technology [DAMD17-02-2-0006]; CDMRP Program in TBI [W81XWH-09-1-0514]; Air Force Office of Scientific Research Military Photomedicine Program [FA9550-11-1-0331] FX NIH grant R01AI050875, Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006), CDMRP Program in TBI (W81XWH-09-1-0514) and Air Force Office of Scientific Research Military Photomedicine Program (FA9550-11-1-0331). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 55 TC 42 Z9 43 U1 1 U2 23 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 7 PY 2013 VL 8 IS 1 AR e53454 DI 10.1371/journal.pone.0053454 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 069IS UT WOS:000313429100069 PM 23308226 ER PT J AU Craft, D Richter, C AF Craft, David Richter, Christian TI Deliverable navigation for multicriteria step and shoot IMRT treatment planning SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID DIRECT APERTURE OPTIMIZATION; NORMAL CONSTRAINT METHOD; PARETO FRONTIER; SURFACES AB We consider Pareto surface based multi-criteria optimization for step and shoot IMRT planning. By analyzing two navigation algorithms, we show both theoretically and in practice that the number of plans needed to form convex combinations of plans during navigation can be kept small (much less than the theoretical maximum number needed in general, which is equal to the number of objectives for on-surface Pareto navigation). Therefore a workable approach for directly deliverable navigation in this setting is to segment the underlying Pareto surface plans and then enforce the mild restriction that only a small number of these plans are active at any time during plan navigation, thus limiting the total number of segments used in the final plan. C1 [Craft, David; Richter, Christian] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Craft, D (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM dcraft@partners.org FU NCI [1 R01 CA103904-01A1] FX This work was supported by NCI grant 1 R01 CA103904-01A1: Multi-criteria IMRT Optimization and by a research collaboration with RaySearch Laboratories. Thanks to Ehsan Salari for helpful feedback on the manuscript. NR 18 TC 9 Z9 9 U1 0 U2 3 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JAN 7 PY 2013 VL 58 IS 1 BP 87 EP 103 DI 10.1088/0031-9155/58/1/87 PG 17 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 056LB UT WOS:000312489800007 PM 23221364 ER PT J AU Unkelbach, J Craft, D Salari, E Ramakrishnan, J Bortfeld, T AF Unkelbach, Jan Craft, David Salari, Ehsan Ramakrishnan, Jagdish Bortfeld, Thomas TI The dependence of optimal fractionation schemes on the spatial dose distribution SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID LINEAR-QUADRATIC MODEL; LUNG-CANCER; HYPOFRACTIONATION; RADIOTHERAPY AB We consider the fractionation problem in radiation therapy. Tumor sites in which the dose-limiting organ at risk (OAR) receives a substantially lower dose than the tumor, bear potential for hypofractionation even if the alpha/beta-ratio of the tumor is larger than the alpha/beta-ratio of the OAR. In this work, we analyze the interdependence of the optimal fractionation scheme and the spatial dose distribution in the OAR. In particular, we derive a criterion under which a hypofractionation regimen is indicated for both a parallel and a serial OAR. The approach is based on the concept of the biologically effective dose (BED). For a hypothetical homogeneously irradiated OAR, it has been shown that hypofractionation is suggested by the BED model if the alpha/beta-ratio of the OAR is larger than alpha/beta-ratio of the tumor times the sparing factor, i.e. the ratio of the dose received by the tumor and the OAR. In this work, we generalize this result to inhomogeneous dose distributions in the OAR. For a parallel OAR, we determine the optimal fractionation scheme by minimizing the integral BED in the OAR for a fixed BED in the tumor. For a serial structure, we minimize the maximum BED in the OAR. This leads to analytical expressions for an effective sparing factor for the OAR, which provides a criterion for hypofractionation. The implications of the model are discussed for lung tumor treatments. It is shown that the model supports hypofractionation for small tumors treated with rotation therapy, i.e. highly conformal techniques where a large volume of lung tissue is exposed to low but nonzero dose. For larger tumors, the model suggests hyperfractionation. We further discuss several non-intuitive interdependencies between optimal fractionation and the spatial dose distribution. For instance, lowering the dose in the lung via proton therapy does not necessarily provide a biological rationale for hypofractionation. C1 [Unkelbach, Jan; Craft, David; Salari, Ehsan; Ramakrishnan, Jagdish; Bortfeld, Thomas] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Unkelbach, Jan; Craft, David; Salari, Ehsan; Ramakrishnan, Jagdish; Bortfeld, Thomas] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Ramakrishnan, Jagdish] MIT, Informat & Decis Syst Lab, Cambridge, MA 02139 USA. RP Unkelbach, J (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM junkelbach@partners.org; tbortfeld@partners.org NR 15 TC 18 Z9 18 U1 0 U2 10 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JAN 7 PY 2013 VL 58 IS 1 BP 159 EP 167 DI 10.1088/0031-9155/58/1/159 PG 9 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 056LB UT WOS:000312489800011 PM 23221166 ER PT J AU Agorastos, A Nash, WP Nunnink, S Yurgil, KA Goldsmith, A Litz, BT Johnson, H Lohr, JB Baker, DG AF Agorastos, Agorastos Nash, William P. Nunnink, Sarah Yurgil, Kate A. Goldsmith, Abigail Litz, Brett T. Johnson, Heather Lohr, James B. Baker, Dewleen G. TI The Peritraumatic Behavior Questionnaire: development and initial validation of a new measure for combat-related peritraumatic reactions SO BMC PSYCHIATRY LA English DT Article DE Peritraumatic behavior questionnaire; Peritraumatic dissociation; Peritraumatic reaction; Posttraumatic stress disorder (PTSD); Stress; Psychometric properties; Validity; Reliability; Screening; Assessment ID POSTTRAUMATIC-STRESS-DISORDER; DISSOCIATIVE EXPERIENCES SCALE; PTSD CHECKLIST PCL; PSYCHOMETRIC PROPERTIES; PSYCHOLOGICAL-ASSESSMENT; DISTRESS INVENTORY; CONTENT VALIDITY; POLICE OFFICERS; NEGATIVE AFFECT; SYMPTOMS AB Background: Posttraumatic stress disorder (PTSD) is one of the most commonly observed stress-related conditions following combat exposure and its effective prevention is a high health-care priority. Reports of peritraumatic reactions have been shown to be highly associated with PTSD among combat exposed service members. However, existing instruments measuring peritraumatic symptoms were not specifically developed to assess combat-related peritraumatic stress and each demonstrates a different peritraumatic focus. We therefore developed the Peritraumatic Behavior Questionnaire (PBQ), a new military-specific rating scale focused upon the wide range of symptoms suggestive of combat-related peritraumatic distress in actively deployed Service Members. This study describes the development of the PBQ and reports on the psychometric properties of its self-rated version (PBQ-SR). Methods: 688 Marine infantry service members were retrospectively assessed by the PBQ-SR within the scope of the Marine Resiliency Study after their deployment to war zone. Participants have been additionally assessed by a variety of questionnaires, as well as clinical interviews both pre and post-deployment. Results: The PBQ-SR demonstrated satisfactory internal consistency, convergent and discriminant validity, as well as high correlation with trait dissociation prior to deployment. Component analysis suggested a latent bi-dimensional structure separating a peritraumatic emotional distress and physical awareness factor. The PBQ-SR total score showed high correlation to general anxiety, depression, poorer general health and posttraumatic symptoms after deployment and remained a significant predictor of PTSD severity, after controlling for those measures. The suggested screening cut-off score of 12 points demonstrated satisfactory predictive power. Conclusions: This study confirms the ability of the PBQ-SR to unify the underlying peritraumatic symptom dimensions and reliably assess combat-related peritraumatic reaction as a general construct. The PBQ-SR demonstrated promise as a potential standard screening measure in military clinical practice, while It's predictive power should be established in prospective studies. C1 [Agorastos, Agorastos; Nunnink, Sarah; Lohr, James B.; Baker, Dewleen G.] VA San Diego, Vet Affairs Ctr Excellence Stress & Mental Hlth, San Diego, CA USA. [Agorastos, Agorastos] Univ Med Ctr Hamburg Eppendorf, Dept Psychiat & Psychotherapy, Hamburg, Germany. [Nash, William P.; Nunnink, Sarah; Goldsmith, Abigail; Lohr, James B.; Baker, Dewleen G.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Nunnink, Sarah; Yurgil, Kate A.; Goldsmith, Abigail; Johnson, Heather; Lohr, James B.; Baker, Dewleen G.] VA San Diego Healthcare System, San Diego, CA USA. [Litz, Brett T.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Litz, Brett T.] Boston Univ, Sch Med, Dept Psychol, Boston, MA 02118 USA. [Litz, Brett T.] VA Boston Healthcare Syst, Natl Ctr Post Traumat Stress Disorder, Boston, MA USA. [Baker, Dewleen G.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. RP Baker, DG (reprint author), VA San Diego, Vet Affairs Ctr Excellence Stress & Mental Hlth, San Diego, CA USA. EM dgbaker@ucsd.edu OI Agorastos, Agorastos/0000-0003-4801-4957 FU Congressionally Directed Medical Research Programs small (pilot) project mechanism [W81XWH-10-1-0693]; VA HSRD [RDIS 0024]; Marine Corps; Navy BUMED FX We would like to acknowledge CAPT. Brian Schumacher who served medical monitor, as well as the Navy Corpsmen at Camp Pendleton who participated in the PBQ development focus group. The "Validation of the Peritraumatic Behavior Questionnaire" study was funded through Congressionally Directed Medical Research Programs small (pilot) project mechanism (Award No.: Contract W81XWH-10-1-0693) (DGB). The linked MRS study is funded by VA HSR&D (Grant No.: RDIS 0024), the Marine Corps and Navy BUMED. We would also like to thank Amela Ahmetovic, Nilima Biswas, William H. Black, Mahalah R. Buell, Teresa Carper, Andrew De La Rosa, Benjamin Dickstein, Caitlin Fernandes, Susan Fesperman, David Fink, Summer Fitzgerald, Steven Gerard, Gali Goldwaser, Patricia Gorman, Jorge A. Gutierrez, John A. Hall, Jr, Christian J. Hansen, Laura Harder, Pia Heppner, Alexandra Kelada, Christopher L. Lehnig, Jennifer Lemmer, Morgan LeSuer-Mandernack, Manjula Mahata, Adam X. Maihofer, Theodore Morrison, Arame Motazedi, Elin Olsson, Ines Pandzic, Anjana H. Patel, Dhaval H. Patel, Sejal Patel, Shetal M. Patel, Taylor Perin-Kash, James O.E. Pittman, Stephanie Raducha, Brenda Thomas, Elisa Tsan, Maria Anna Valencerina, Chelsea Wallace, Kuixing Zhang, and the many intermittent on-site MRS clinician-interviewers and data collection staff. NR 75 TC 3 Z9 3 U1 3 U2 17 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-244X J9 BMC PSYCHIATRY JI BMC Psychiatry PD JAN 5 PY 2013 VL 13 AR 9 DI 10.1186/1471-244X-13-9 PG 11 WC Psychiatry SC Psychiatry GA 102DI UT WOS:000315823300001 PM 23289606 ER PT J AU Teerlink, JR Cotter, G Davison, BA Felker, GM Filippatos, G Greenberg, BH Ponikowski, P Unemori, E Voors, AA Adams, KF Dorobantu, MI Grinfeld, LR Jondeau, G Marmor, A Masip, J Pang, PS Werdan, K Teichman, SL Trapani, A Bush, CA Saini, R Schumacher, C Severin, TM Metra, M AF Teerlink, John R. Cotter, Gad Davison, Beth A. Felker, G. Michael Filippatos, Gerasimos Greenberg, Barry H. Ponikowski, Piotr Unemori, Elaine Voors, Adriaan A. Adams, Kirkwood F., Jr. Dorobantu, Maria I. Grinfeld, Liliana R. Jondeau, Guillaume Marmor, Alon Masip, Josep Pang, Peter S. Werdan, Karl Teichman, Sam L. Trapani, Angelo Bush, Christopher A. Saini, Rajnish Schumacher, Christoph Severin, Thomas M. Metra, Marco CA RELAXin Acute Heart Failure RELAX- TI Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial SO LANCET LA English DT Article ID RENAL-FUNCTION; PROTECT; DYSPNEA; HOSPITALIZATION; ROLOFYLLINE; ANTAGONIST; OUTCOMES; ASSOCIATION; MORTALITY; LEVOSIMENDAN AB Background Serelaxin, recombinant human relaxin-2, is a vasoactive peptide hormone with many biological and haemodynamic effects. In a pilot study, serelaxin was safe and well tolerated with positive clinical outcome signals in patients with acute heart failure. The RELAX-AHF trial tested the hypothesis that serelaxin-treated patients would have greater dyspnoea relief compared with patients treated with standard care and placebo. Methods RELAX-AHF was an international, double-blind, placebo-controlled trial, enrolling patients admitted to hospital for acute heart failure who were randomly assigned (1:1) via a central randomisation scheme blocked by study centre to standard care plus 48-h intravenous infusions of placebo or serelaxin (30 mu g/kg per day) within 16 h from presentation. All patients had dyspnoea, congestion on chest radiograph, increased brain natriuretic peptide (BNP) or N-terminal prohormone of BNP, mild-to-moderate renal insufficiency, and systolic blood pressure greater than 125 mm Hg. Patients, personnel administering study drug, and those undertaking study-related assessments were masked to treatment assignment. The primary endpoints evaluating dyspnoea improvement were change from baseline in the visual analogue scale area under the curve (VAS AUC) to day 5 and the proportion of patients with moderate or marked dyspnoea improvement measured by Likert scale during the first 24 h, both analysed by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00520806. Findings 1161 patients were randomly assigned to serelaxin (n=581) or placebo (n=580). Serelaxin improved the VAS AUC primary dyspnoea endpoint (448 mm x h, 95% CI 120-775; p=0.007) compared with placebo, but had no significant effect on the other primary endpoint (Likert scale; placebo, 150 patients [26%]; serelaxin, 156 [27%]; p=0.70). No significant effects were recorded for the secondary endpoints of cardiovascular death or readmission to hospital for heart failure or renal failure (placebo, 75 events [60-day Kaplan-Meier estimate, 13.0%]; serelaxin, 76 events [13.2%]; hazard ratio [HR] 1.02 [0.74-1.41], p=0.89] or days alive out of the hospital up to day 60 (placebo, 47.7 [SD 12.1] days; serelaxin, 48.3 [11.6]; p=0.37). Serelaxin treatment was associated with significant reductions of other prespecified additional endpoints, including fewer deaths at day 180 (placebo, 65 deaths; serelaxin, 42; HR 0.63, 95% CI 0.42-0.93; p=0.019). Interpretation Treatment of acute heart failure with serelaxin was associated with dyspnoea relief and improvement in other clinical outcomes, but had no effect on readmission to hospital. Serelaxin treatment was well tolerated and safe, supported by the reduced 180-day mortality. C1 [Teerlink, John R.] San Francisco VA Med Ctr, Div Cardiol, San Francisco, CA 94121 USA. [Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Cotter, Gad; Davison, Beth A.] Momentum Res, Durham, NC USA. [Felker, G. Michael] Duke Univ, Sch Med, Durham, NC USA. [Felker, G. Michael] Duke Univ, Med Ctr, Duke Heart Ctr, Durham, NC 27710 USA. [Filippatos, Gerasimos] Athens Univ Hosp, Athens, Greece. [Greenberg, Barry H.] Univ Calif San Diego, San Diego, CA 92103 USA. [Ponikowski, Piotr] Med Univ, Clin Mil Hosp, Wroclaw, Poland. [Unemori, Elaine; Teichman, Sam L.] Corthera, San Carlos, CA USA. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Gronignen, Groningen, Netherlands. [Adams, Kirkwood F., Jr.] Univ N Carolina, Chapel Hill, NC USA. [Dorobantu, Maria I.] Floreasca Emergency Clin Hosp, Bucharest, Romania. [Grinfeld, Liliana R.] Univ Buenos Aires, Buenos Aires, DF, Argentina. [Jondeau, Guillaume] Univ Paris 07, Hop Bichat, Paris, France. [Marmor, Alon] Ziv Med Ctr, Safed, Israel. [Masip, Josep] Univ Barcelona, Consorci Sanitari Integral, Barcelona, Spain. [Pang, Peter S.] Northwestern Univ, Chicago, IL 60611 USA. [Werdan, Karl] Univ Halle Wittenberg, Halle, Saale, Germany. [Trapani, Angelo; Bush, Christopher A.; Saini, Rajnish] Novartis Pharmaceut, E Hanover, NJ USA. [Schumacher, Christoph; Severin, Thomas M.] Novartis Pharmaceut, Basel, Switzerland. [Metra, Marco] Univ Brescia, Brescia, Italy. RP Teerlink, JR (reprint author), San Francisco VA Med Ctr, Div Cardiol, San Francisco, CA 94121 USA. EM john.teerlink@ucsf.edu RI Lainscak, Mitja/F-3237-2015; Ponikowski, Piotr/O-6454-2015; OI Ponikowski, Piotr/0000-0002-3391-7064; Metra, Marco/0000-0001-6691-8568; Davison, Beth/0000-0003-2374-6449 FU Corthera; Amgen; Bayer; Cardio3 Bioscience; Cytokinetics; Merck; Novartis; Takeda; Teva; Trevena; Otsuka; Roche Diagnostics; NHLBI; Nanosphere; European Union; Abbott; PDL BioPharma; Alere; Cardio3Biosciences; Celladon; Ceva; European Committee; Dutch Heart Foundation; Servier; Torrent; Vifor; Duke Clinical Research Institute; Momentum Research; Abbott Vascular FX JRT has received research grants or consulting fees from Amgen, Bayer, Corthera, Cardio3 Bioscience, Cytokinetics, Merck, Novartis, Takeda, Teva, and Trevena. GC and BAD are employees of Momentum Research, which has provided consulting and trial management services to NovaCardia, Merck, Corthera, Novartis, Nile Therapeutics, Bioheart, Cardio3 Biosciences, Amgen, Celadon, Targegen, Trevena, Sorbent Therapeutics, and NIH. GMF reports consulting income from Novartis, Medpace, Amgen, Otsuka, Trevena, Roche Diagnostics, Merck, BG Medicine, Medtronic, and St Judes and grant fundings from Amgen, Otsuka, Roche Diagnostics, and NHLBI. GF is an executive committee member and consultant to Corthera (a Novartis company), Bayer, Cardiorentis, and has received research grants from Amgen, Nanosphere, European Union. BHG served as a consultant for Corthera and Novartis. PP was a consultant for Astellas, Bayer, EKR Therapeutics, J&J, the Medicines Company, Medtronic, Novartis, Otsuka, Palatin Technologies, PDL BioPharma, Pericor Therapeutics, SigmaTau, Solvay Pharmaceuticals, and Trevena; has received honoraria from Alere, Beckman-Coulter, BiogenIdec, Corthera, Ikaria, Nile Therapeutics, Momentum Research, and Overcome; has received research support from Abbott, Merck and PDL BioPharma; and has received travel support from MyLife and equipment support from Sonosite. EU is employed by the sponsor, Corthera (a Novartis company). AAV has received consultancy fees and/or research grants from Alere, Bayer, Cardio3Biosciences, Celladon, Ceva, European Committee, Dutch Heart Foundation, Novartis, Servier, Torrent, and Vifor. KFA has received research grants and consulting fees from Corthera, Merck, Roche Diagnostics, and Duke Clinical Research Institute; research grants from Novartis and Amgen; and consulting fees from Momentum Research. MID, LRG, JG, AM, JM, and KW have received research grants from Corthera (a Novartis affiliate company). KW received personal support for travel to meetings for the RELAX-AHF trial. KW's institution received honorarium for patient enrolment in the RELAX-AHF trial and honorarium for national coordinatorship of KW for the RELAX-AHF trial. PSP has been a consultant for Astellas, Bayer, EKR Therapeutics, J&J, the Medicines Company, Medtronic, Novartis, Otsuka, Palatin Technologies, PDL BioPharma, Pericor Therapeutics, SigmaTau, Solvay Pharmaceuticals, Trevena; received honoraria from Alere, Beckman-Coulter, BiogenIdec, Corthera, Ikaria, Nile Therapeutics, Momentum Research, and Overcome; received research support from Abbott, Merck, and PDL BioPharma; and received travel support from MyLife and equipment support from Sonosite. SLT was an employee of the sponsor, Corthera (a Novartis affiliate company). AT, CAB, RS, CS, and TMS are Novartis employees and receive salary, benefits, and stock options from Novartis Pharmaceuticals Corporation (CAB, RS, AT) or Novartis Pharma (CS, TS). MM has received consulting income from Abbott Vascular, Bayer, Corthera, and Novartis, as well as travel support and honoraria from Servier and Novartis. NR 43 TC 314 Z9 331 U1 6 U2 61 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD JAN 5 PY 2013 VL 381 IS 9860 BP 29 EP 39 DI 10.1016/S0140-6736(12)61855-8 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 064AW UT WOS:000313044300024 PM 23141816 ER PT J AU Koutsioumpa, M Polytarchou, C Courty, J Zhang, Y Kieffer, N Mikelis, C Skandalis, SS Hellman, U Iliopoulos, D Papadimitriou, E AF Koutsioumpa, Marina Polytarchou, Christos Courty, Jose Zhang, Yue Kieffer, Nelly Mikelis, Constantinos Skandalis, Spyros S. Hellman, Ulf Iliopoulos, Dimitrios Papadimitriou, Evangelia TI Interplay between alpha(v)beta(3) Integrin and Nucleolin Regulates Human Endothelial and Glioma Cell Migration SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SURFACE-EXPRESSED NUCLEOLIN; GROWTH-FACTOR; IN-VITRO; ANGIOGENIC FUNCTION; TUMOR VASCULATURE; BETA(3) INTEGRIN; RECEPTOR; PROTEIN; ACTIVATION; BINDS AB The multifunctional protein nucleolin (NCL) is overexpressed on the surface of activated endothelial and tumor cells and mediates the stimulatory actions of several angiogenic growth factors, such as pleiotrophin (PTN). Because alpha(v)beta(3) integrin is also required for PTN-induced cell migration, the aim of the present work was to study the interplay between NCL and alpha(v)beta(3) by using biochemical, immunofluorescence, and proximity ligation assays in cells with genetically altered expression of the studied molecules. Interestingly, cell surface NCL localization was detected only in cells expressing alpha(v)beta(3) and depended on the phosphorylation of beta(3) at Tyr(773) through receptor protein-tyrosine phosphatase beta/zeta (RPTP beta/zeta) and c-Src activation. Downstream of alpha(v)beta(3), PI3K activity mediated this phenomenon and cell surface NCL was found to interact with both alpha(v)beta(3) and RPTP beta/zeta. Positive correlation of cell surface NCL and alpha(v)beta(3) expression was also observed in human glioblastoma tissue arrays, and inhibition of cell migration by cell surface NCL antagonists was observed only in cells expressing alpha(v)beta(3). Collectively, these data suggest that both expression and beta(3) integrin phosphorylation at Tyr(773) determine the cell surface localization of NCL downstream of the RPTP beta/zeta/c-Src signaling cascade and can be used as a biomarker for the use of cell surface NCL antagonists as anticancer agents. C1 [Koutsioumpa, Marina; Mikelis, Constantinos; Papadimitriou, Evangelia] Univ Patras, Dept Pharm, Mol Pharmacol Lab, GR-26504 Patras, Greece. [Polytarchou, Christos; Iliopoulos, Dimitrios] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. [Polytarchou, Christos; Iliopoulos, Dimitrios] Harvard Univ, Dept Immunobiol & Microbiol, Sch Med, Boston, MA 02115 USA. [Courty, Jose] Univ Paris 12, Lab CRRET, F-94010 Creteil, France. [Zhang, Yue; Kieffer, Nelly] Jiao Tong Univ, CNRS LIA 124, Sinofrench Res Ctr Life Sci & Genom, Rui Jin Hosp,Med Sch, Shanghai 200025, Peoples R China. [Skandalis, Spyros S.; Hellman, Ulf] Uppsala Univ, Ludwig Inst Canc Res, SE-75105 Uppsala, Sweden. RP Papadimitriou, E (reprint author), Univ Patras, Dept Pharm, Mol Pharmacol Lab, GR-26504 Patras, Greece. EM epapad@upatras.gr RI Skandalis, Spyros/F-6815-2010 FU European Union (European Social Fund); Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF)-Research Funding Program: "Heracleitus II, and Investing in Knowledge Society through the European Social Fund" FX This work was supported by the European Union (European Social Fund) and Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF)-Research Funding Program: "Heracleitus II, and Investing in Knowledge Society through the European Social Fund." NR 62 TC 19 Z9 19 U1 0 U2 16 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 4 PY 2013 VL 288 IS 1 BP 343 EP 354 DI 10.1074/jbc.M112.387076 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 066CJ UT WOS:000313197200036 PM 23161541 ER PT J AU Sarkar, A Hochedlinger, K AF Sarkar, Abby Hochedlinger, Konrad TI The Sox Family of Transcription Factors: Versatile Regulators of Stem and Progenitor Cell Fate SO CELL STEM CELL LA English DT Review ID SEX-DETERMINING REGION; SELF-RENEWAL; GENE-EXPRESSION; NEURAL CREST; DNA-BINDING; TGF-BETA; NEURONAL DIFFERENTIATION; REPROGRAMMING FACTORS; HUMAN FIBROBLASTS; IDENTIFIES SOX2 AB Sox family transcription factors are well-established regulators of cell fate decisions during development. Accumulating evidence documents that they play additional roles in adult tissue homeostasis and regeneration. Remarkably, forced expression of Sox factors, in combination with other synergistic factors, reprograms differentiated cells into somatic or pluripotent stem cells. Dysregulation of Sox factors has been further implicated in diseases including cancer. Here, we review molecular and functional evidence linking Sox proteins with stem cell biology, cellular reprogramming, and disease with an emphasis on Sox2. C1 [Sarkar, Abby; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Howard Hughes Med Inst, Boston, MA 02114 USA. [Sarkar, Abby; Hochedlinger, Konrad] Ctr Regenerat Med, Boston, MA 02114 USA. [Sarkar, Abby; Hochedlinger, Konrad] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Sarkar, Abby; Hochedlinger, Konrad] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Sarkar, Abby; Hochedlinger, Konrad] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Hochedlinger, K (reprint author), Massachusetts Gen Hosp, Ctr Canc, Howard Hughes Med Inst, 185 Cambridge St, Boston, MA 02114 USA. EM khochedlinger@helix.mgh.harvard.edu FU HHMI, NIH [DP2OD003266, R01HD058013, R01DK96034]; Harvard Stem Cell Institute FX This Review is dedicated to the memory of Larysa Pevny, who has made seminal contributions to the study of the biology of Sox factors. We apologize to those colleagues whose work we could not cite due to space constraints. We thank Hanno Hock, Michael Rendl, and members of the Hochedlinger laboratory for suggestions and critical reading of the manuscript. K.H. was supported by HHMI, NIH (DP2OD003266, R01HD058013, and R01DK96034), and the Harvard Stem Cell Institute. NR 141 TC 203 Z9 212 U1 7 U2 106 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 3 PY 2013 VL 12 IS 1 BP 15 EP 30 DI 10.1016/j.stem.2012.12.007 PG 16 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 074UM UT WOS:000313839500007 PM 23290134 ER PT J AU Snider, AJ Ruiz, P Obeid, LM Oates, JC AF Snider, Ashley J. Ruiz, Phillip Obeid, Lina M. Oates, Jim C. TI Inhibition of Sphingosine Kinase-2 in a Murine Model of Lupus Nephritis SO PLOS ONE LA English DT Article ID RENAL THROMBOXANE PRODUCTION; MRL/LPR MICE; ERYTHEMATOSUS; SURVIVAL; FTY720; SPHINGOSINE-1-PHOSPHATE; DISEASE; CYCLOOXYGENASE-2; INFLAMMATION; ASSOCIATION AB Sphingosine-1-phosphate (S1P), a potent bioactive lipid, is emerging as a central mediator in inflammation and immune responses. We have previously implicated S1P and its synthetic enzyme sphingosine kinase (SK) in inflammatory and autoimmune disorders, including inflammatory bowel disease and rheumatoid arthritis. Generation of S1P requires phosphorylation of sphingosine by SK, of which there are two isoforms. Numerous studies have implicated SK1 in immune cell trafficking, inflammation and autoimmune disorders. In this study, we set out to determine the role of SK and S1P in lupus nephritis (LN). To this end, we examined S1P and dihydro-S1P (dh-S1P) levels in serum and kidney tissues from a mouse model of LN. Interestingly dh-S1P was significantly elevated in serum and kidney tissue from LN mice, which is more readily phosphorylated by SK2. Therefore, we employed the use of the specific SK2 inhibitor, ABC294640 in our murine model of LN. Treatment with ABC294640 did not improve vascular or interstitial pathology associated with LN. However, mice treated with the SK2 inhibitor did demonstrate decreases in glomerular pathology and accumulation of B and T cells in the spleen these were not statistically different from lpr mice treated with vehicle. LN mice treated with ABC294640 did not have improved urine thromboxane levels or urine proteinuria measurements. Both S1P and dh-S1P levels in circulation were significantly reduced with ABC294640 treatment; however, dh-S1P was actually elevated in kidneys from LN mice treated with ABC294640. Together these data demonstrate a role for SKs in LN; however, they suggest that inhibition of SK1 or perhaps both SK isoforms would better prevent elevations in S1P and dh-S1P and potentially better protect against LN. C1 [Snider, Ashley J.; Obeid, Lina M.; Oates, Jim C.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Snider, Ashley J.; Obeid, Lina M.; Oates, Jim C.] Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. [Ruiz, Phillip] Univ Miami, Miller Sch Med, Dept Pathol, Div Immunopathol, Miami, FL 33136 USA. [Obeid, Lina M.] Med Univ S Carolina, Dept Mol & Cellular Biol & Pathobiol, Charleston, SC 29425 USA. RP Oates, JC (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. EM oatesjc@musc.edu OI obeid, lina/0000-0002-0734-0847 FU Alliance for Lupus Research; Veterans Affairs Merit Award; Career Development Award FX This work was supported by a grant from the Alliance for Lupus Research (JCO), Veterans Affairs Merit Award (LMO) and Career Development Award (AJS). Lipid analyses provided by the Lipidomics Shared Resource, Hollings Cancer Center, Medical University of South Carolina (P30 CA138313) and the Lipidomics Core in the SC Lipidomics and Pathobiology COBRE, Department Biochemistry, MUSC (P20 RR017677). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 30 TC 10 Z9 10 U1 0 U2 33 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 3 PY 2013 VL 8 IS 1 AR e53521 DI 10.1371/journal.pone.0053521 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 070BE UT WOS:000313480000063 PM 23301082 ER PT J AU Theodoropoulou, S Brodowska, K Kayama, M Morizane, Y Miller, JW Gragoudas, ES Vavvas, DG AF Theodoropoulou, Sofia Brodowska, Katarzyna Kayama, Maki Morizane, Yuki Miller, Joan W. Gragoudas, Evangelos S. Vavvas, Demetrios G. TI Aminoimidazole Carboxamide Ribonucleotide (AICAR) Inhibits the Growth of Retinoblastoma In Vivo by Decreasing Angiogenesis and Inducing Apoptosis SO PLOS ONE LA English DT Article ID ACTIVATED PROTEIN-KINASE; MESSENGER-RNA TRANSLATION; SKELETAL-MUSCLE; ENERGY STATUS; TUMOR-GROWTH; PHOSPHORYLATION SITES; SIGNALING PATHWAY; MAMMALIAN TARGET; CDK INHIBITORS; BREAST-CANCER AB 5-Aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR), an analog of AMP is widely used as an activator of AMP-kinase (AMPK), a protein that regulates the responses of the cell to energy change. Recently, we showed that AICAR-induced AMPK activation inhibits the growth of retinoblastoma cells in vitro by decreasing cyclins and by inducing apoptosis and S-phase arrest. In this study, we investigated the effects of AMPK activator AICAR on the growth of retinoblastoma in vivo. Intraperitoneal injection of AICAR resulted in 48% growth inhibition of Y79 retinoblastoma cell tumors in mice. Tumors isolated from mice treated with AICAR had decreased expression of Ki67 and increased apoptotic cells (TUNEL positive) compared with the control. In addition, AICAR treatment suppressed significantly tumor vessel density and macrophage infiltration. We also showed that AICAR administration resulted in AMPK activation and mTOR pathway inhibition. Paradoxically observed down-regulation of p21, which indicates that p21 may have a novel function of an oncogene in retinoblastoma tumor. Our results indicate that AICAR treatment inhibited the growth of retinoblastoma tumor in vivo via AMPK/mTORC1 pathway and by apoptogenic, anti-proliferative, anti-angiogenesis mechanism. AICAR is a promising novel non-chemotherapeutic drug that may be effective as an adjuvant in treating Retinoblastoma. C1 [Theodoropoulou, Sofia; Brodowska, Katarzyna; Kayama, Maki; Morizane, Yuki; Miller, Joan W.; Gragoudas, Evangelos S.; Vavvas, Demetrios G.] Harvard Univ, Sch Med, Retina Serv,Angiogenesis Lab, Dept Ophthalmol,Massachusetts Eye & Ear Infirmary, Boston, MA 02115 USA. RP Vavvas, DG (reprint author), Harvard Univ, Sch Med, Retina Serv,Angiogenesis Lab, Dept Ophthalmol,Massachusetts Eye & Ear Infirmary, Boston, MA 02115 USA. EM vavvas@meei.harvard.edu OI Vavvas, Demetrios/0000-0002-8622-6478 FU National Eye Institute grant [EY014104]; Research to Prevent Blindness Unrestricted Institutional Award FX This work was supported by National Eye Institute grant EY014104 (MEEI Core Grant) and Research to Prevent Blindness Unrestricted Institutional Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; This work was supported by National Eye Institute grant EY014104 (MEEI Core Grant) and Research to Prevent Blindness Unrestricted Institutional Award. NR 66 TC 13 Z9 16 U1 1 U2 17 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 3 PY 2013 VL 8 IS 1 AR e52852 DI 10.1371/journal.pone.0052852 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 070BE UT WOS:000313480000018 PM 23300996 ER PT J AU Volz, MS Suarez-Contreras, V Mendonca, ME Pinheiro, FS Merabet, LB Fregni, F AF Volz, Magdalena Sarah Suarez-Contreras, Vanessa Mendonca, Mariana E. Pinheiro, Fernando Santos Merabet, Lotfi B. Fregni, Felipe TI Effects of Sensory Behavioral Tasks on Pain Threshold and Cortical Excitability SO PLOS ONE LA English DT Article ID DIRECT-CURRENT STIMULATION; TRANSCRANIAL MAGNETIC STIMULATION; ELECTRICAL NERVE-STIMULATION; PRIMARY SOMATOSENSORY CORTEX; MOTOR CORTEX; NEUROPATHIC PAIN; MACAQUE MONKEY; MEDIAL PAIN; SYSTEM; PLASTICITY AB Background/Objective: Transcutaneous electrical stimulation has been proven to modulate nervous system activity, leading to changes in pain perception, via the peripheral sensory system, in a bottom up approach. We tested whether different sensory behavioral tasks induce significant effects in pain processing and whether these changes correlate with cortical plasticity. Methodology/Principal Findings: This randomized parallel designed experiment included forty healthy right-handed males. Three different somatosensory tasks, including learning tasks with and without visual feedback and simple somatosensory input, were tested on pressure pain threshold and motor cortex excitability using transcranial magnetic stimulation (TMS). Sensory tasks induced hand-specific pain modulation effects. They increased pain thresholds of the left hand ( which was the target to the sensory tasks) and decreased them in the right hand. TMS showed that somatosensory input decreased cortical excitability, as indexed by reduced MEP amplitudes and increased SICI. Although somatosensory tasks similarly altered pain thresholds and cortical excitability, there was no significant correlation between these variables and only the visual feedback task showed significant somatosensory learning. Conclusions/Significance: Lack of correlation between cortical excitability and pain thresholds and lack of differential effects across tasks, but significant changes in pain thresholds suggest that analgesic effects of somatosensory tasks are not primarily associated with motor cortical neural mechanisms, thus, suggesting that subcortical neural circuits and/or spinal cord are involved with the observed effects. Identifying the neural mechanisms of somatosensory stimulation on pain may open novel possibilities for combining different targeted therapies for pain control. C1 [Volz, Magdalena Sarah; Suarez-Contreras, Vanessa; Mendonca, Mariana E.; Pinheiro, Fernando Santos; Fregni, Felipe] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Lab Neuromodulat,Dept Phys Med & Rehabil, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Volz, Magdalena Sarah] Charite Univ Med Berlin, Charite Ctr Neurol Neurosurg & Psychiat, Berlin, Germany. [Merabet, Lotfi B.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Fregni, F (reprint author), Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Lab Neuromodulat,Dept Phys Med & Rehabil, Boston, MA 02115 USA. EM fregni.felipe@mgh.harvard.edu FU National Institutes of Health (NIH) grant [R21 DK081773-03] FX This work was supported by a National Institutes of Health (NIH) grant (R21 DK081773-03). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 5 Z9 6 U1 0 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 3 PY 2013 VL 8 IS 1 AR e52968 DI 10.1371/journal.pone.0052968 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 070BE UT WOS:000313480000022 PM 23301010 ER PT J AU Sartelli, M Catena, F Ansaloni, L Moore, E Malangoni, M Velmahos, G Coimbra, R Koike, K Leppaniemi, A Biffl, W Balogh, Z Bendinelli, C Gupta, S Kluger, Y Agresta, F di Saverio, S Tugnoli, G Jovine, E Ordonez, C Gomes, CA Pereira, GA Yuan, KC Bala, M Peev, MP Cui, YF Marwah, S Zachariah, S Sakakushev, B Kong, V Ahmed, A Abbas, A Gonsaga, RAT Guercioni, G Vettoretto, N Poiasina, E Ben-Ishay, O Diaz-Nieto, R Massalou, D Skrovina, M Gerych, I Augustin, G Kenig, J Khokha, V Trana, C Kok, KYY Mefire, AC Lee, JG Hong, SK Lohse, HAS Ghnnam, W Verni, A Lohsiriwat, V Siribumrungwong, B Tavares, A Baiocchi, G Das, K Jarry, J Zida, M Sato, N Murata, K Shoko, T Irahara, T Hamedelneel, AO Naidoo, N Adesunkanmi, ARK Kobe, Y Attri, AK Sharma, R Coccolini, F El Zalabany, T Al Khalifa, K Sanjuan, J Barnabe, R Ishii, W AF Sartelli, Massimo Catena, Fausto Ansaloni, Luca Moore, Ernest Malangoni, Mark Velmahos, George Coimbra, Raul Koike, Kaoru Leppaniemi, Ari Biffl, Walter Balogh, Zsolt Bendinelli, Cino Gupta, Sanjay Kluger, Yoram Agresta, Ferdinando di Saverio, Salomone Tugnoli, Gregorio Jovine, Elio Ordonez, Carlos Gomes, Carlos Augusto Pereira Junior, Gerson Alves Yuan, Kuo-Ching Bala, Miklosh Peev, Miroslav P. Cui, Yunfeng Marwah, Sanjay Zachariah, Sanoop Sakakushev, Boris Kong, Victor Ahmed, Adamu Abbas, Ashraf Teixeira Gonsaga, Ricardo Alessandro Guercioni, Gianluca Vettoretto, Nereo Poiasina, Elia Ben-Ishay, Offir Diaz-Nieto, Rafael Massalou, Damien Skrovina, Matej Gerych, Ihor Augustin, Goran Kenig, Jakub Khokha, Vladimir Trana, Cristian Kok, Kenneth Yuh Yen Chichom Mefire, Alain Lee, Jae Gil Hong, Suk-Kyung Segovia Lohse, Helmut Alfredo Ghnnam, Wagih Verni, Alfredo Lohsiriwat, Varut Siribumrungwong, Boonying Tavares, Alberto Baiocchi, Gianluca Das, Koray Jarry, Julien Zida, Maurice Sato, Norio Murata, Kiyoshi Shoko, Tomohisa Irahara, Takayuki Hamedelneel, Ahmed O. Naidoo, Noel Adesunkanmi, Abdul Rashid Kayode Kobe, Yoshiro Attri, A. K. Sharma, Rajeev Coccolini, Federico El Zalabany, Tamer Al Khalifa, Khalid Sanjuan, Juan Barnabe, Rita Ishii, Wataru TI Complicated intra-abdominal infections in a worldwide context: an observational prospective study (CIAOW Study) SO WORLD JOURNAL OF EMERGENCY SURGERY LA English DT Review ID PERCUTANEOUS DRAINAGE; SECONDARY PERITONITIS; FLUID COLLECTIONS; ABSCESSES; RELAPAROTOMY AB Despite advances in diagnosis, surgery, and antimicrobial therapy, mortality rates associated with complicated intra-abdominal infections remain exceedingly high. The World Society of Emergency Surgery (WSES) has designed the CIAOW study in order to describe the clinical, microbiological, and management-related profiles of both community- and healthcare-acquired complicated intra-abdominal infections in a worldwide context. The CIAOW study (Complicated Intra-Abdominal infection Observational Worldwide Study) is a multicenter observational study currently underway in 57 medical institutions worldwide. The study includes patients undergoing surgery or interventional drainage to address complicated intra-abdominal infections. This preliminary report includes all data from almost the first two months of the six-month study period. Patients who met inclusion criteria with either community-acquired or healthcare-associated complicated intra-abdominal infections (IAIs) were included in the study. 702 patients with a mean age of 49.2 years (range 18-98) were enrolled in the study. 272 patients (38.7%) were women and 430 (62.3%) were men. Among these patients, 615 (87.6%) were affected by community-acquired IAIs while the remaining 87 (12.4%) suffered from healthcare-associated infections. Generalized peritonitis was observed in 304 patients (43.3%), whereas localized peritonitis or abscesses was registered in 398 (57.7%) patients. The overall mortality rate was 10.1% (71/702). The final results of the CIAOW Study will be published following the conclusion of the study period in March 2013. C1 [Sartelli, Massimo] Macerata Hosp, Dept Surg, Macerata, Italy. [Catena, Fausto] Maggiore Parma Hosp, Parma, Italy. [Ansaloni, Luca; Poiasina, Elia; Coccolini, Federico] Osped Riuniti Bergamo, Dept Gen Surg, I-24100 Bergamo, Italy. [Moore, Ernest; Biffl, Walter] Denver Hlth Med Ctr, Dept Surg, Denver, CO USA. [Malangoni, Mark] Amer Board Surg, Philadelphia, PA USA. [Velmahos, George; Peev, Miroslav P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA USA. [Coimbra, Raul] UC San Diego Hlth Syst, Dept Surg, San Diego, CA USA. [Koike, Kaoru; Sato, Norio] Kyoto Univ, Grad Sch Med, Dept Primary Care & Emergency Med, Kyoto, Japan. [Leppaniemi, Ari] Univ Hosp Meilahti, Dept Abdominal Surg, Helsinki, Finland. [Balogh, Zsolt; Bendinelli, Cino] Univ Newcastle, Dept Surg, Newcastle, NSW 2300, Australia. [Gupta, Sanjay; Attri, A. K.; Sharma, Rajeev] Govt Med Coll & Hosp, Dept Surg, Chandigarh, India. [Kluger, Yoram; Ben-Ishay, Offir] Rambam Hlth Care Campus, Dept Gen Surg, Haifa, Israel. [Agresta, Ferdinando] Adria Hosp, Dept Surg, Adria, Italy. [di Saverio, Salomone; Tugnoli, Gregorio] Maggiore Hosp, Trauma Surg Unit, Bologna, Italy. [Jovine, Elio; Barnabe, Rita] Maggiore Hosp, Dept Surg, Bologna, Italy. [Ordonez, Carlos; Sanjuan, Juan] Univ Valle, Dept Surg, Fdn Valle del Lili, Cali, Colombia. [Gomes, Carlos Augusto] Monte Sinai Hosp, Dept Surg, Juiz De Fora, Brazil. [Pereira Junior, Gerson Alves] Dept Surg, Emergency Unit, Ribeirao Preto, Brazil. [Yuan, Kuo-Ching] Chang Gung Mem Hosp, Dept Surg, Tao Yuan, Taiwan. [Bala, Miklosh] Hadassah Med Ctr, Dept Gen Surg, IL-91120 Jerusalem, Israel. [Cui, Yunfeng] Tianjin Med Univ, Tianjin Nankai Hosp, Nankai Clin Sch Med, Dept Surg, Tianjin, Peoples R China. [Marwah, Sanjay] Pt BDS Postgrad Inst Med Sci, Dept Surg, Rohtak, Haryana, India. [Zachariah, Sanoop] MOSC Med Coll, Dept Surg, Cochin, Kerala, India. [Sakakushev, Boris] Univ Hosp UMBAL St George Plovdiv, Clin Gen Surg 1, Plovdiv, Bulgaria. [Sakakushev, Boris] Med Univ Univ Hosp St George, Gen Surg Clin, Plovdiv, Bulgaria. [Kong, Victor] Edendale Hosp, Dept Surg, Pietermaritzburg, South Africa. [Ahmed, Adamu] Ahmadu Bello Univ Teaching Hosp Zaria, Dept Surg, Kaduna, Nigeria. [Abbas, Ashraf] Mansoura Univ Hosp, Dept Surg, Mansoura, Egypt. [Teixeira Gonsaga, Ricardo Alessandro] Fac Integradas Padre Albino, Dept Surg, Catanduva, Brazil. [Guercioni, Gianluca] Mazzoni Hosp, Dept Surg, Ascoli Piceno, Italy. [Vettoretto, Nereo] Mellini Hosp, Dept Surg, Chiari, BS, Italy. [Diaz-Nieto, Rafael] Univ Hosp, Dept Gen & Digest Surg, Malaga, Spain. [Massalou, Damien] Univ Nice Sophia Antipolis, Univ Hosp Nice, Dept Gen Surg & Surg Oncol, Nice, France. [Skrovina, Matej] Hosp & Oncol Ctr, Dept Surg, Novy Jicin, Czech Republic. [Gerych, Ihor] Lviv Emergency Hosp, Dept Gen Surg, Lvov, Ukraine. [Augustin, Goran] Univ Hosp Ctr Zagreb, Dept Surg, Zagreb, Croatia. [Kenig, Jakub] Jagiellonian Univ, Narutowicz Hosp, Dept Gen Surger 3, Krakow, Poland. [Khokha, Vladimir] Mozyr City Hosp, Dept Surg, Mozyr, Byelarus. [Trana, Cristian] Univ Ancona, Dept Surg, Ancona, Italy. [Kok, Kenneth Yuh Yen] Ripas Hosp, Dept Surg, Bandar Seri Begawan, Brunei. [Chichom Mefire, Alain] Reg Hosp Limbe, Limbe, Cameroon. [Chichom Mefire, Alain] Reg Hosp Buea, Limbe, Cameroon. [Lee, Jae Gil] Yonsei Univ, Coll Med, Severance Hosp, Dept Surg, Seoul, South Korea. [Hong, Suk-Kyung] Univ Ulsan, Dept Surg, Div Trauma & Surg Crit Care, Seoul, South Korea. [Segovia Lohse, Helmut Alfredo] Hosp Clin, Catedra Clin Quirurg 2, Asuncion, Paraguay. [Ghnnam, Wagih] Khamis Mushayt Gen Hosp, Dept Surg, Khamis Mushayt, Saudi Arabia. [Verni, Alfredo] Cutral Co Clin, Dept Surg, Neuquen, Argentina. [Lohsiriwat, Varut] Siriraj Hosp, Fac Med, Dept Surg, Bangkok, Thailand. [Siribumrungwong, Boonying] Thammasat Univ Hosp, Dept Surg, Pathum Thani, Thailand. [Tavares, Alberto] Hosp Reg Alta Especialidad Bajio, Dept Surg, Leon, Mexico. [Baiocchi, Gianluca] Univ Brescia, Dept Clin & Expt Sci, Brescia, Italy. [Das, Koray] Adana Numune Training & Res Hosp, Adana, Turkey. [Jarry, Julien] Mil Hosp Desgenettes, Lyon, France. [Zida, Maurice] Teaching Hosp Yalgado Ouedraogo, Ouagadougou, Burkina Faso. [Murata, Kiyoshi] Tokyo Med & Dent Univ, Dept Acute & Crit Care Med, Tokyo, Japan. [Shoko, Tomohisa] Matsudo City Hosp, Shock Trauma & Emergency Med Ctr, Chiba, Japan. [Irahara, Takayuki] Tama Nagayama Hosp, Nippon Med Sch, Emergency & Crit Care Ctr, Tokyo, Japan. [Hamedelneel, Ahmed O.] Our Lady Lourdes Hosp, Dept Surg, Drogheda, Ireland. [Naidoo, Noel] Port Shepstone Hosp, Dept Surg, Port Shepstone, South Africa. [Adesunkanmi, Abdul Rashid Kayode] Obafemi Awolowo Univ Hosp, Coll Hlth Sci, Dept Surg, Ife, Nigeria. [Kobe, Yoshiro] Chiba Univ Hosp, Dept Emergency & Crit Care Med, Chiba, Japan. [El Zalabany, Tamer; Al Khalifa, Khalid] Bahrain Def Force Hosp, Dept Surg, Manama, Bahrain. [Ishii, Wataru] Kyoto Second Red Cross Hosp, Dept Emergency Med, Kyoto, Japan. RP Sartelli, M (reprint author), Macerata Hosp, Dept Surg, Macerata, Italy. EM m.sartelli@virgilio.it RI Gonsaga, Ricardo Alessandro T/I-3346-2012; Kok, Kenneth/F-3264-2013; Balogh, Zsolt/A-2002-2010; ghnnam, wagih/I-5212-2013; OI Sakakushev, Boris/0000-0001-8399-0115; ZACHARIAH, SANOOP KOSHY/0000-0003-2405-5842; Gonsaga, Ricardo Alessandro T/0000-0001-7495-4366; Balogh, Zsolt/0000-0002-0277-4822; ghnnam, wagih/0000-0003-3599-9929; Chichom-Mefire, Alain/0000-0001-7230-567X; Agresta, Ferdinando/0000-0002-6114-1881; Ansaloni, Luca/0000-0001-6427-0307; Augustin, Goran/0000-0002-0202-3324; Di Saverio, Salomone/0000-0001-5685-5022 NR 15 TC 15 Z9 15 U1 2 U2 16 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1749-7922 J9 WORLD J EMERG SURG JI World J. Emerg. Surg. PD JAN 3 PY 2013 VL 8 AR 1 DI 10.1186/1749-7922-8-1 PG 7 WC Emergency Medicine; Surgery SC Emergency Medicine; Surgery GA 073BN UT WOS:000313718400001 PM 23286785 ER PT J AU Hong, FX Kahl, BS Gray, R AF Hong, Fangxin Kahl, Brad S. Gray, Robert TI Incremental value in outcome prediction with gene expression-based signatures in diffuse large B-cell lymphoma SO BLOOD LA English DT Article ID SURVIVAL; RECLASSIFICATION AB Multiple gene expression-based signatures have been identified in diffuse large B-cell lymphoma that are predictive for survival outcomes. Most studies assess predictive significance based on P values from multivariable Cox regression. Few investigations have evaluated the incremental usefulness of these signatures. Recent developments in statistical methodology extend the use of concordance measures on censored survival data. We applied these methods to evaluate the added value in survival risk prediction from 3 published gene-based signatures on 2 sets of patients with diffuse large B-cell lymphoma treated with CHOP or R-CHOP. Our results indicate these gene-based signatures are inferior to clinical factors and provide little added value in risk assessment. To develop highly discriminating risk prediction models, we need to use appropriate approaches and consider more than gene expression. However, the study of gene expression and clinical outcomes retains considerable potential to enhance understanding of disease mechanisms and uncover new therapeutic targets. (Blood. 2013; 121(1): 156-158) C1 [Hong, Fangxin; Gray, Robert] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Kahl, Brad S.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. RP Hong, FX (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. EM fxhong@jimmy.harvard.edu FU Department of Biostatistics and Computational Biology R.S. fund FX This study was funded by the Department of Biostatistics and Computational Biology R.S. fund. NR 15 TC 7 Z9 7 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 3 PY 2013 VL 121 IS 1 BP 156 EP 158 DI 10.1182/blood-2012-08-450106 PG 3 WC Hematology SC Hematology GA 065EH UT WOS:000313130400022 PM 23160463 ER PT J AU Barry, ER Morikawa, T Butler, BL Shrestha, K de la Rosa, R Yan, KS Fuchs, CS Magness, ST Smits, R Ogino, S Kuo, CJ Camargo, FD AF Barry, Evan R. Morikawa, Teppei Butler, Brian L. Shrestha, Kriti de la Rosa, Rosemarie Yan, Kelley S. Fuchs, Charles S. Magness, Scott T. Smits, Ron Ogino, Shuji Kuo, Calvin J. Camargo, Fernando D. TI Restriction of intestinal stem cell expansion and the regenerative response by YAP SO NATURE LA English DT Article ID HIPPO SIGNALING PATHWAY; WNT/BETA-CATENIN; COLORECTAL-CANCER; IN-VITRO; MOUSE MODEL; EXPRESSION; HOMEOSTASIS; EPITHELIUM; CRYPT; LGR5 AB A remarkable feature of regenerative processes is their ability to halt proliferation once an organ's structure has been restored. The Wnt signalling pathway is the major driving force for homeostatic self-renewal and regeneration in the mammalian intestine. However, the mechanisms that counterbalance Wnt-driven proliferation are poorly understood. Here we demonstrate in mice and humans that yes-associated protein 1 (YAP; also known as YAP1)-a protein known for its powerful growth-inducing and oncogenic properties(1,2)-has an unexpected growth-suppressive function, restricting Wnt signals during intestinal regeneration. Transgenic expression of YAP reduces Wnt target gene expression and results in the rapid loss of intestinal crypts. In addition, loss of YAP results in Wnt hypersensitivity during regeneration, leading to hyperplasia, expansion of intestinal stem cells and niche cells, and formation of ectopic crypts and microadenomas. We find that cytoplasmic YAP restricts elevated Wnt signalling independently of the AXIN-APC-GSK-3 beta complex partly by limiting the activity of dishevelled (DVL). DVL signals in the nucleus of intestinal stem cells, and its forced expression leads to enhanced Wnt signalling in crypts. YAP dampens Wnt signals by restricting DVL nuclear translocation during regenerative growth. Finally, we provide evidence that YAP is silenced in a subset of highly aggressive and undifferentiated human colorectal carcinomas, and that its expression can restrict the growth of colorectal carcinoma xenografts. Collectively, our work describes a novel mechanistic paradigm for how proliferative signals are counterbalanced in regenerating tissues. Additionally, our findings have important implications for the targeting of YAP in human malignancies. C1 [Barry, Evan R.; Butler, Brian L.; Shrestha, Kriti; de la Rosa, Rosemarie; Camargo, Fernando D.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Barry, Evan R.; Butler, Brian L.; Shrestha, Kriti; de la Rosa, Rosemarie; Camargo, Fernando D.] Childrens Hosp, Dept Hematol Oncol, Boston, MA 02115 USA. [Barry, Evan R.; Butler, Brian L.; Camargo, Fernando D.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Barry, Evan R.; Camargo, Fernando D.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Morikawa, Teppei; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Morikawa, Teppei; Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Yan, Kelley S.; Kuo, Calvin J.] Stanford Univ, Dept Med, Div Hematol, Stanford, CA 94305 USA. [Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Fuchs, Charles S.; Ogino, Shuji] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Magness, Scott T.] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. [Magness, Scott T.] Univ N Carolina, Dept Biomed Engn, Chapel Hill, NC 27599 USA. [Smits, Ron] Erasmus MC, Dept Gastroenterol & Hepatol, NL-3000 CA Rotterdam, Netherlands. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Camargo, FD (reprint author), Childrens Hosp, Stem Cell Program, 300 Longwood Ave, Boston, MA 02115 USA. EM Fernando.camargo@childrens.harvard.edu FU Stand Up to Cancer-AACR initiative; National Institutes of Health [R01 CA131426, AR064036]; Harvard Stem Cell Institute; American Cancer Society Illinois Division [PF-12-245-01-CCG]; CIRM [1K08DK096048]; [1U01DK085527]; [R01 CA151993]; [R01 DK091427]; [P01CA87969]; [P50CA127003] FX We thank L. Zon and Camargo laboratory members for critical review of this manuscript and X. He for Myc-DVL2 constructs. This work was supported by grants from the Stand Up to Cancer-AACR initiative (F. D. C.), National Institutes of Health R01 CA131426 and AR064036 (F. D. C.) and the Harvard Stem Cell Institute (F. D. C.). F. D. C. is a Pew Scholar in the Biomedical Sciences. E. R. B. is supported by a postdoctoral fellowship from the American Cancer Society Illinois Division (PF-12-245-01-CCG). This work has also benefited from support to K.S.Y. (CIRM, and 1K08DK096048), C.J.K. (1U01DK085527), S.O. (R01 CA151993 and R01 DK091427), S. T. M. (P01CA87969) and C. S. F. (P50CA127003). NR 39 TC 161 Z9 164 U1 8 U2 103 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 3 PY 2013 VL 493 IS 7430 BP 106 EP + DI 10.1038/nature11693 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 062QC UT WOS:000312933800040 PM 23178811 ER PT J AU Leng, SY Nallamothu, BK Saint, S Appleman, LJ Bump, GM AF Leng, Siyang Nallamothu, Brahmajee K. Saint, Sanjay Appleman, Leonard J. Bump, Gregory M. TI Simple and Complex SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MYELOPROLIFERATIVE DISORDERS; ESSENTIAL THROMBOCYTHEMIA; POLYCYTHEMIA-VERA; MYELOFIBROSIS; THROMBOSIS; DIAGNOSIS; NEOPLASMS; RUXOLITINIB; MANAGEMENT; DISEASE C1 [Leng, Siyang; Appleman, Leonard J.; Bump, Gregory M.] Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA USA. [Appleman, Leonard J.] Univ Pittsburgh, Med Ctr, Div Hematol Oncol, Pittsburgh, PA USA. [Nallamothu, Brahmajee K.; Saint, Sanjay] VA Ann Arbor Healthcare Syst, Dept Internal Med, Ann Arbor, MI USA. [Nallamothu, Brahmajee K.] VA Ann Arbor Healthcare Syst, Div Cardiol, Ann Arbor, MI USA. Univ Michigan Hlth Syst, Ann Arbor, MI USA. RP Leng, SY (reprint author), VA Pittsburgh Healthcare Syst, Univ Dr 130-U, Pittsburgh, PA 15240 USA. EM siyang.leng@gmail.com OI Appleman, Leonard/0000-0003-4951-7388 NR 16 TC 1 Z9 1 U1 1 U2 5 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 3 PY 2013 VL 368 IS 1 BP 65 EP 71 DI 10.1056/NEJMcps1202256 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 062PA UT WOS:000312930600008 PM 23281978 ER PT J AU Kressin, NR Atz, JM AF Kressin, Nancy R. Atz, Joshua M. TI Mind the Outcomes SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Kressin, Nancy R.] VA Boston Healthcare Syst, Boston, MA USA. [Kressin, Nancy R.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Atz, Joshua M.] Manchester Vet Clin, Manchester, CT USA. RP Kressin, NR (reprint author), VA Boston Healthcare Syst, Boston, MA USA. EM nkressin@bu.edu FU NHLBI NIH HHS [1U01HL105342] NR 6 TC 0 Z9 0 U1 0 U2 4 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 2 PY 2013 VL 309 IS 1 BP 39 EP 40 DI 10.1001/jama.2012.153826 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 146TB UT WOS:000319113000024 PM 23280222 ER PT J AU Kelly, JD Barrie, MB Ross, RA Temple, BA Moses, LM Bausch, DG AF Kelly, J. Daniel Barrie, M. Bailor Ross, Rachel A. Temple, Brian A. Moses, Lina M. Bausch, Daniel G. TI Housing equity for health equity: a rights-based approach to the control of Lassa fever in post-war Sierra Leone SO BMC INTERNATIONAL HEALTH AND HUMAN RIGHTS LA English DT Article DE Lassa fever; Arenavirus; Mastomys natalensis; Housing equity; Health equity; Public health; Global health ID MASTOMYS-NATALENSIS; WEST-AFRICA; RODENTS; VIRUS; RISK; EPIDEMIOLOGY; TANZANIA AB Poor quality housing is an infringement on the rights of all humans to a standard of living adequate for health. Among the many vulnerabilities of those without adequate shelter is the risk of disease spread by rodents and other pests. One such disease is Lassa fever, an acute and sometimes severe viral hemorrhagic illness endemic in West Africa. Lassa virus is maintained in the rodent Mastomys natalensis, commonly known as the "multimammate rat," which frequently invades the domestic environment, putting humans at risk of Lassa fever. The highest reported incidence of Lassa fever in the world is consistently in the Kenema District of Sierra Leone, a region that was at the center of Sierra Leone's civil war in which tens of thousands of lives were lost and hundreds of thousands of dwellings destroyed. Despite the end of the war in 2002, most of Kenema's population still lives in inadequate housing that puts them at risk of rodent invasion and Lassa fever. Furthermore, despite years of health education and village hygiene campaigns, the incidence of Lassa fever in Kenema District appears to be increasing. We focus on Lassa fever as a matter of human rights, proposing a strategy to improve housing quality, and discuss how housing equity has the potential to improve health equity and ultimately economic productivity in Sierra Leone. The manuscript is designed to spur discussion and action towards provision of housing and prevention of disease in one of the world's most vulnerable populations. C1 [Kelly, J. Daniel] Baylor Coll Med, Houston, TX 77030 USA. [Barrie, M. Bailor] Coll Med & Allied Hlth Sci, Freetown, Sierra Leone. [Ross, Rachel A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Temple, Brian A.] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA. [Moses, Lina M.; Bausch, Daniel G.] Tulane Sch Publ Hlth & Trop Med, Dept Trop Med, New Orleans, LA 70112 USA. [Bausch, Daniel G.] Doctors Global Hlth, Atlanta, GA USA. RP Bausch, DG (reprint author), Tulane Sch Publ Hlth & Trop Med, Dept Trop Med, 1430 Tulane Ave SL 17, New Orleans, LA 70112 USA. EM dbausch@tulane.edu NR 31 TC 5 Z9 5 U1 1 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-698X J9 BMC INT HEALTH HUM R JI BMC Int. Health Hum. Rights. PD JAN 2 PY 2013 VL 13 AR 2 DI 10.1186/1472-698X-13-2 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 096LC UT WOS:000315404500001 PM 23282054 ER PT J AU Das De, S Vranceanu, AM Ring, DC AF Das De, Soumen Vranceanu, Ana-Maria Ring, David C. TI Contribution of Kinesophobia and Catastrophic Thinking to Upper-Extremity-Specific Disability SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID FEAR-AVOIDANCE BELIEFS; LOW-BACK-PAIN; COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; SELF-REPORTED DISABILITY; QUALITY-OF-LIFE; MUSCULOSKELETAL PAIN; TAMPA SCALE; PSYCHOMETRIC PROPERTIES; SHOULDER PAIN AB Background: Upper-extremity-specific disability correlates with mood and coping strategies. The aim of this study was to determine if two psychological factors, kinesiophobia (fear of movement) and perceived partner support, contribute significantly to variation in upper-extremity-specific disability in a model that included factors known to contribute to variation such as depression, pain anxiety, and catastrophic thinking. Methods: We performed an observational cross-sectional study of 319 patients who each had one of the following conditions: trigger finger (n = 94), carpal tunnel syndrome (n = 29), trapeziometacarpal arthrosis (n = 33), Dupuytren contracture (n = 31), de Quervain syndrome (n = 28), wrist ganglion cyst (n = 32), lateral epicondylosis (n = 41), and a fracture of the distal part of the radius treated nonoperatively six weeks previously (n = 31). Each patient completed the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire and questionnaires measuring symptoms of depression, pain anxiety, catastrophic thinking, kinesiophobia, and perceived level of support from a partner or significant other. Stepwise multiple linear regression was used to determine significant independent predictors of the DASH score. Results: Men had significantly lower (better) DASH scores than women (21 versus 31; p < 0.01). DASH scores also differed significantly by diagnosis (p < 0.01), marital status (p = 0.047), and employment status (p < 0.01). The DASH score correlated significantly with depressive symptoms (p < 0.01), catastrophic thinking (p < 0.01), kinesiophobia (p < 0.01), and pain anxiety (p < 0.01) but not with perceived partner support. The best multivariable model of factors associated with greater arm-specific disability (according to the DASH score) included sex, diagnosis, employment status, catastrophic thinking, and kinesiophobia and accounted for 55% of the variation. Conclusions: In this sample, kinesiophobia and catastrophic thinking were the most important predictors of upper-extremity-specific disability in a model that accounted for symptoms of depression, anxiety, and pathophysiology (diagnosis) and explained more than half of the variation in disability. Perceived partner support was not a significant factor. The consistent and predominant role of several modifiable psychological factors in disability suggests that patients may benefit from a multidisciplinary approach that optimizes mindset and coping strategies. C1 [Das De, Soumen; Vranceanu, Ana-Maria; Ring, David C.] Massachusetts Gen Hosp, Dept Orthopaed Surg, MGH Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr 2100, Boston, MA 02114 USA. RP Das De, S (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, MGH Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr 2100, 55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 36 TC 29 Z9 29 U1 1 U2 16 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD JAN 2 PY 2013 VL 95A IS 1 BP 76 EP 81 DI 10.2106/JBJS.L.00064 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 073QF UT WOS:000313756900011 PM 23283376 ER PT J AU Loi, S Michiels, S Baselga, J Bartlett, JMS Singhal, SK Sabine, VS Sims, AH Sahmoud, T Dixon, JM Piccart, MJ Sotiriou, C AF Loi, Sherene Michiels, Stefan Baselga, Jose Bartlett, John M. S. Singhal, Sandeep K. Sabine, Vicky S. Sims, Andrew H. Sahmoud, Tarek Dixon, J. Michael Piccart, Martine J. Sotiriou, Christos TI PIK3CA Genotype and a PIK3CA Mutation-Related Gene Signature and Response to Everolimus and Letrozole in Estrogen Receptor Positive Breast Cancer SO PLOS ONE LA English DT Article ID ENDOCRINE THERAPY; EXPRESSION; CELLS; PI3K; SENSITIVITY; APOPTOSIS; MODELS; MTOR; AKT AB The phosphatidylinositol 39 kinase (PI3K) pathway is commonly activated in breast cancer and aberrations such as PI3K mutations are common. Recent exciting clinical trial results in advanced estrogen receptor-positive (ER) breast cancer support mTOR activation is a major means of estrogen-independent tumor growth. Hence the means to identify a responsive breast cancer population that would most benefit from these compounds in the adjuvant or earlier stage setting is of high interest. Here we study PIK3CA genotype as well as a previously reported PI3K/mTOR-pathway gene signature (PIK3CA-GS) and their ability to estimate the level of PI3K pathway activation in two clinical trials of newly diagnosed ER-positive breast cancer patients- a total of 81 patients- one of which was randomized between letrozole and placebo vs letrozole and everolimus. The main objectives were to correlate the baseline PIK3CA genotype and GS with the relative change from baseline to day 15 in Ki67 (which has been shown to be prognostic in breast cancer) and phosphorylated S6 (S240) immunohistochemistry (a substrate of mTOR). In the randomized dataset, the PIK3CA-GS could identify those patients with the largest relative decreases in Ki67 to letrozole/everolimus (R = -0.43, p = 0.008) compared with letrozole/ placebo (R = 0.07, p = 0.58; interaction test p = 0.02). In a second dataset of pre-surgical everolimus alone, the PIK3CA-GS was not significantly correlated with relative change in Ki67 (R = -0.11, p = 0.37) but with relative change in phosphorlyated S6 (S240) (R = -0.46, p = 0.028). PIK3CA genotype was not significantly associated with any endpoint in either datasets. Our results suggest that the PIK3CA-GS has potential to identify those ER-positive BCs who may benefit from the addition of everolimus to letrozole. Further evaluation of the PIK3CA-GS as a predictive biomarker is warranted as it may facilitate better selection of responsive patient populations for mTOR inhibition in combination with letrozole. C1 [Loi, Sherene; Michiels, Stefan; Singhal, Sandeep K.; Sotiriou, Christos] Inst Jules Bordet, Breast Canc Translat Res Lab BCTL, B-1000 Brussels, Belgium. [Baselga, Jose] Massachusetts Gen Hosp, Ctr Canc, Div Hematol & Oncol, Boston, MA USA. [Bartlett, John M. S.; Sabine, Vicky S.] Univ Edinburgh, Western Gen Hosp, Canc Res Ctr, Endocrine Canc Grp, Edinburgh, Midlothian, Scotland. [Bartlett, John M. S.] Ontario Inst Canc Res, Toronto, ON, Canada. [Sims, Andrew H.] Univ Edinburgh, Western Gen Hosp, Inst Genet & Mol Med, Edinburgh Breast Unit, Edinburgh, Midlothian, Scotland. [Sahmoud, Tarek] Novartis Pharmaceut, E Hanover, NJ USA. [Dixon, J. Michael] Univ Edinburgh, Western Gen Hosp, Appl Bioinformat Canc Grp, Canc Res Ctr,Inst Genet & Mol Med,Edinburgh Break, Edinburgh, Midlothian, Scotland. [Piccart, Martine J.] Inst Jules Bordet, Dept Med, B-1000 Brussels, Belgium. RP Loi, S (reprint author), Inst Jules Bordet, Breast Canc Translat Res Lab BCTL, B-1000 Brussels, Belgium. EM sherene.loi@bordet.be RI Michiels, Stefan/L-1516-2013; Loi, Sherene/H-1979-2016; Sims, Andrew/E-4819-2012 OI Michiels, Stefan/0000-0002-6963-2968; Loi, Sherene/0000-0001-6137-9171; Sims, Andrew/0000-0001-9082-3665 FU JC Fonds Heuson, Belgium; Estee Lauder Breast Cancer Research Foundation, NY FX SL and CS are supported by the JC Fonds Heuson, Belgium and the Estee Lauder Breast Cancer Research Foundation, NY. The authors acknowledge the Edinburgh Cancer Medicine Centre and Cancer Research UK for tissue banking support for dataset B. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Novartis Pharma did not provide any financial support for research reported in this manuscript. NR 23 TC 37 Z9 37 U1 0 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 2 PY 2013 VL 8 IS 1 AR e53292 DI 10.1371/journal.pone.0053292 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 067UP UT WOS:000313320900073 PM 23301057 ER PT J AU Eisen, HN Chakraborty, AK AF Eisen, Herman N. Chakraborty, Arup K. TI Immunopaleontology reveals how affinity enhancement is achieved during affinity maturation of antibodies to influenza virus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID IMMUNE-RESPONSE; HEMAGGLUTININ; SPECIFICITY; ANTIGEN; CELLS C1 [Eisen, Herman N.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Eisen, Herman N.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Eisen, Herman N.; Chakraborty, Arup K.] Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02129 USA. [Eisen, Herman N.; Chakraborty, Arup K.] Harvard Univ, Boston, MA 02129 USA. [Chakraborty, Arup K.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Chakraborty, Arup K.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Chakraborty, Arup K.] MIT, Dept Phys, Cambridge, MA 02139 USA. [Chakraborty, Arup K.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Chakraborty, Arup K.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. RP Eisen, HN (reprint author), MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM hneisen@mit.edu; arupc@mit.edu NR 24 TC 4 Z9 4 U1 0 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 2 PY 2013 VL 110 IS 1 BP 7 EP 8 DI 10.1073/pnas.1219396110 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 071XI UT WOS:000313630300019 PM 23284164 ER PT J AU Chen, XQ Burdett, TC Desjardins, CA Logan, R Cipriani, S Xu, YH Schwarzschild, MA AF Chen, Xiqun Burdett, Thomas C. Desjardins, Cody A. Logan, Robert Cipriani, Sara Xu, Yuehang Schwarzschild, Michael A. TI Disrupted and transgenic urate oxidase alter urate and dopaminergic neurodegeneration SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ADENOSINE A(2A) RECEPTORS; URIC-ACID PROTECTS; PARKINSONS-DISEASE; DEFICIENT MICE; PC12 CELLS; RAT MODEL; IN-VIVO; ANTIOXIDANT; NEURONS; PROGRESSION AB Urate is the end product of purine metabolism in humans, owing to the evolutionary disruption of the gene encoding urate oxidase (UOx). Elevated urate can cause gout and urolithiasis and is associated with cardiovascular and other diseases. However, urate also possesses antioxidant and neuroprotective properties. Recent convergence of epidemiological and clinical data has identified urate as a predictor of both reduced risk and favorable progression of Parkinson's disease (PD). In rodents, functional UOx catalyzes urate oxidation to allantoin. We found that UOx KO mice with a constitutive mutation of the gene have increased concentrations of brain urate. By contrast, UOx transgenic (Tg) mice overexpressing the enzyme have reduced brain urate concentrations. Effects of the complementary UOx manipulations were assessed in a mouse intrastriatal 6-hydroxydopamine (6-OHDA) model of hemiparkinsonism. UOx KO mice exhibit attenuated toxic effects of 6-OHDA on nigral dopaminergic cell counts, striatal dopamine content, and rotational behavior. Conversely, Tg overexpression of UOx exacerbates these morphological, neurochemical, and functional lesions of the dopaminergic nigrostriatal pathway. Together our data support a neuroprotective role of endogenous urate in dopaminergic neurons and strengthen the rationale for developing urate-elevating strategies as potential disease-modifying therapy for PD. C1 [Chen, Xiqun; Burdett, Thomas C.; Desjardins, Cody A.; Logan, Robert; Cipriani, Sara; Xu, Yuehang; Schwarzschild, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02129 USA. RP Chen, XQ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02129 USA. EM xchen17@partners.org FU RJG Foundation; Michael J. Fox Foundation; American Federation for Aging Research Beeson Collaborative Program; National Institutes of Health [R21NS058324, K24NS060991]; DoD [W81XWH-11-1-0150] FX The authors thank Kenneth L. Rock and Hajime Kono for generously providing UOx Tg mice and for advice on their use; and Alberto Serrano-Pozo for his assistance in stereological cell counting. This work is supported by the RJG Foundation, Michael J. Fox Foundation, American Federation for Aging Research Beeson Collaborative Program, and by National Institutes of Health Grants R21NS058324, K24NS060991, and DoD W81XWH-11-1-0150. NR 43 TC 33 Z9 34 U1 0 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 2 PY 2013 VL 110 IS 1 BP 300 EP 305 DI 10.1073/pnas.1217296110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 071XI UT WOS:000313630300067 PM 23248282 ER PT J AU Fitch, KV Looby, SE Rope, A Eneh, P Hemphill, L Lee, H Grinspoon, SK AF Fitch, Kathleen V. Looby, Sara E. Rope, Alison Eneh, Peace Hemphill, Linda Lee, Hang Grinspoon, Steven K. TI Effects of aging and smoking on carotid intima-media thickness in HIV-infection SO AIDS LA English DT Article DE aging; cardiovascular diseases; HIV; smoking ID IMMUNODEFICIENCY-VIRUS-INFECTION; CARDIOVASCULAR RISK-FACTORS; SUBCLINICAL CORONARY ATHEROSCLEROSIS; COMBINATION ANTIRETROVIRAL THERAPY; MULTICENTER AIDS COHORT; GENERAL-POPULATION; DISEASE RISK; MYOCARDIAL-INFARCTION; METABOLIC SYNDROME; CELL COUNT AB Objectives: To investigate the effects of aging and smoking on carotid intima-media thickness (cIMT) among patients with and without HIV. Methods: Data from a community sample of HIV-infected and HIV-uninfected participants were analyzed. Carotid intima-media thickness was measured via carotid ultrasound and smoking history was obtained via patient interview. Results: Data on 166 male and female participants with stable HIV-infection and 152 healthy HIV-uninfected participants were analyzed. Among the HIV-infected and HIV-uninfected participants, a significant association was observed between age and cIMT [r = 0.51, P <0.0001 (HIV), r= 0.39, P <0.0001, (non-HIV)], and between smoking burden and cIMT [r= 0.42, P<0.0001 (HIV), r=0.24, P=0.003 (non-HIV)]. In multi-variate regression modeling among all participants (HIV and non-HIV), a significant three-way interaction was observed between age, smoking burden, and HIV status with respect to cIMT (P< 0.010), controlling for sex, race, and traditional cardiovascular disease (CVD) risk factors, such that increased cIMT was associated with increased smoking burden and age to a greater degree among HIV-infected vs. HIV-uninfected participants. Among HIV-infected participants a significant interaction between smoking burden and age with respect to cIMT was seen (P=0.027) controlling for race, sex, CVD risk factors, immunological function, and antiretroviral therapy use. Conclusion: A significant interaction between HIV, age, and smoking on cIMT was observed, suggesting that HIV-infection modifies the relationship of age and smoking on cIMT in this population. These findings emphasize the need to encourage smoking cessation in this population, due to its deleterious effect on subclinical atherosclerosis in older HIV-infected patients. (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins AIDS 2013, 27:49-57 C1 [Fitch, Kathleen V.; Looby, Sara E.; Rope, Alison; Eneh, Peace; Grinspoon, Steven K.] Massachusetts Gen Hosp, MGH Program Nutr Metab, Boston, MA 02114 USA. [Hemphill, Linda] Massachusetts Gen Hosp, Div Cardiovasc, Boston, MA 02114 USA. [Lee, Hang] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, MGH Program Nutr Metab, LON5-207,55 Fruit St, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NIH [R01 DK049302, K24 DK064545-08, P30 DK040561, M01-RR-01066, 1 UL1 RR025758-01, K23 NR011833-01A1]; Harvard Clinical and Translational Science Center; National Center for Research Resources; Mary Fisher Clinical AIDS Research and Education (CARE) Fund FX Funding was provided by NIH R01 DK049302, K24 DK064545-08, and P30 DK040561 to S.K.G., and by NIH M01-RR-01066 and 1 UL1 RR025758-01, Harvard Clinical and Translational Science Center, from the National Center for Research Resources and from the Mary Fisher Clinical AIDS Research and Education (CARE) Fund. NIH funding also provided through K23 NR011833-01A1 to S.E.L. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. NR 38 TC 11 Z9 12 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JAN 2 PY 2013 VL 27 IS 1 BP 49 EP 57 DI 10.1097/QAD.0b013e328358b29c PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 054QJ UT WOS:000312358000007 PM 22874518 ER PT J AU Singh, J AF Singh, Jasvinder TI FOLIC ACID SUPPLEMENTATION FOR RHEUMATOID ARTHRITIS PATIENTS ON METHOTREXATE: THE GOOD GETS BETTER SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Editorial Material DE Rheumatology ID LOW-DOSE METHOTREXATE; MODIFYING ANTIRHEUMATIC DRUGS; RECOMMENDATIONS; TRIAL C1 [Singh, Jasvinder] Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35233 USA. [Singh, Jasvinder] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL USA. [Singh, Jasvinder] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, J (reprint author), Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35233 USA. EM jasvinder.md@gmail.com NR 11 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X EI 1361-6137 J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2013 IS 7 AR ED000063 DI 10.1002/14651858.ED000063 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA AQ8AY UT WOS:000343044400002 PM 24151647 ER PT S AU Benton, RG Choubey, S Clark, DG Johnsten, T Raghavan, VV AF Benton, Ryan G. Choubey, Suresh Clark, David G. Johnsten, Tom Raghavan, Vijay V. BE Imamura, K Usui, S Shirao, T Kasamatsu, T Schwabe, L Zhong, N TI Diagnosis and Grading of Alzheimer's Disease via Automatic Classification of FDG-PET Scans SO BRAIN AND HEALTH INFORMATICS SE Lecture Notes in Artificial Intelligence LA English DT Proceedings Paper CT International Conference on Brain and Health Informatics (BHI) CY OCT 29-31, 2013 CL Maebashi, JAPAN SP Web Intelligence Consortium, IEEE Computat Intelligence Soc Task Force on Brain Informat, Maebashi Inst Technol, Gunma Prefecture Govt, Maebashi City Govt, Maebashi Convent Bur, Web Intelligence Lab Inc, Mitsuba Gakki Co Ltd, GCC Inc, Japan High Comm, Kuribara Med Instruments, Yamato Inc DE Alzheimer's Disease; PET; Mild Cognitive Impairment ID DEMENTIA AB Clinical trials for interventions that seek to delay the onset of Alzheimer's disease (AD) are hampered by inadequate methods for selecting study subjects who are at risk, and who may therefore benefit from the interventions being studied. Automated monitoring tools may facilitate clinical research and thereby reduce the impact of AD on individuals, caregivers, society at large, and government healthcare infrastructure. We studied the 18F-deoxyglucose positron emission tomography (FDG-PET) scans of research subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI), using a Machine Learning technique. Three hundred ninety-four FDG-PET scans were obtained from the ADNI database. An automated procedure was used to extract measurements from 31 regions of each PET surface projection. These data points were used to evaluate the sensitivity and specificity of support vector machine (SVM) classifiers and to compare both Linear and Radial-Basis SVM techniques against a classic thresholding method used in earlier work. C1 [Benton, Ryan G.; Raghavan, Vijay V.] Univ Louisiana Lafayette, Ctr Adv Comp Studies, Lafayette, LA 70504 USA. [Choubey, Suresh] Qual Operat GE Healthcare, Birmingham, AL USA. [Clark, David G.] Birmingham VA Med Ctr, Birmingham, AL USA. [Clark, David G.] Univ Alabama Birmingham, Dept Neurol, Birmingham, AL USA. [Johnsten, Tom] Univ S Alabama, Sch Comp, Mobile, AL USA. RP Benton, RG (reprint author), Univ Louisiana Lafayette, Ctr Adv Comp Studies, Lafayette, LA 70504 USA. EM rbenton@cacs.louisiana.edu; suresh.choubey@ge.com; dgclark@gmail.com; tjohnsten@southalabama.edu; vijay@cacs.louisiana.edu FU Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health [U01 AG024904] FX Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904). ADNI data are disseminated by the Laboratory for Neuro- Imaging at the University of California, Los Angeles. NR 15 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-319-02753-1; 978-3-319-02752-4 J9 LECT NOTES ARTIF INT PY 2013 VL 8211 BP 266 EP 276 PG 11 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Medical Informatics SC Computer Science; Medical Informatics GA BB3HY UT WOS:000342795600027 ER PT S AU Onorati, F Barbieri, R Mauri, M Russo, V Mainardi, L AF Onorati, Francesco Barbieri, Riccardo Mauri, Maurizio Russo, Vincenzo Mainardi, Luca GP IEEE TI Reconstruction and Analysis of the Pupil Dilation Signal: Application to a Psychophysiological Affective Protocol SO 2013 35TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 35th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society (EMBC) CY JUL 03-07, 2013 CL Osaka, JAPAN SP IEEE Engn Med Biol Soc, Japanese Soc Med & Biol Engn ID FLUCTUATIONS; SIZE AB Pupil dilation (PD) dynamics reflect the interactions of sympathetic and parasympathetic innervations in the iris muscle. Different pupillary responses have been observed with respect to emotionally characterized stimuli. Evidences of the correlation between PD and respiration, heart rate variability (HRV) and blood pressure (BP) are present in literature, making the pupil dilation a candidate for estimating the activity state of the Autonomic Nervous System (ANS), in particular during stressful and/or emotionally characterized stimuli. The aim of this study is to investigate whether both slow and fast PD dynamics can be addressed to characterized different affective states. Two different frequency bands were considered: the classical autonomic band [0-0.45] Hz and a very high frequency (VHF) band [0.45-5] Hz. The pupil dilation signals from 13 normal subjects were recorded during a psychological protocol suitable to evoke particular affective states. An elaborate reconstruction of the missing data (blink events and artifacts) was performed to obtain a more reliable signal, particularly in the VHF band. Results show a high correlation between the arousal of the event and the power characteristics of the signal, in all frequencies. In particular, for the "Anger" condition, we can observe 10 indices out of 13 significantly different with respect to "Baseline" counterparts. These preliminary results suggest that both slow and fast oscillations of the PD can be used to characterize affective states. C1 [Onorati, Francesco; Mainardi, Luca] Politecn Milan, Dipartimento Elettron Informaz & Bioingn, Milan, Italy. [Onorati, Francesco; Mauri, Maurizio; Russo, Vincenzo] IULM Univ, Ist Comunicazione Comportamento Consum, Milan, Italy. [Onorati, Francesco; Barbieri, Riccardo] MIT, Cambridge, MA USA. [Onorati, Francesco; Barbieri, Riccardo] Massachussets Gen Hosp, Boston, MA USA. RP Onorati, F (reprint author), Politecn Milan, Dipartimento Elettron Informaz & Bioingn, Milan, Italy. OI Barbieri, Riccardo/0000-0001-9381-3833 NR 22 TC 0 Z9 0 U1 0 U2 4 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4577-0216-7 J9 IEEE ENG MED BIO PY 2013 BP 5 EP 8 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BB2DX UT WOS:000341702100001 ER PT S AU Prerau, MJ Purdon, PL Eden, UT AF Prerau, Michael J. Purdon, Patrick L. Eden, Uri T. GP IEEE TI Tracking Non-Stationary Spectral Peak Structure in EEG Data SO 2013 35TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 35th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society (EMBC) CY JUL 03-07, 2013 CL Osaka, JAPAN SP IEEE Engn Med Biol Soc, Japanese Soc Med & Biol Engn ID INSTANTANEOUS FREQUENCY AB We develop a particle filter algorithm to simultaneously estimate and track the instantaneous peak frequency, amplitude, and bandwidth of multiple concurrent non-stationary components of an EEG signal in the time-frequency domain. We use this method to characterize human EEG activity during anesthesia-induced unconsciousness. C1 [Prerau, Michael J.; Purdon, Patrick L.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA 02129 USA. RP Prerau, MJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 149 13th St, Charlestown, MA 02129 USA. EM prerau@nmr.mgh.harvard.edu; patrickp@nmr.mgh.harvard.edu; tzvi@bu.edu NR 7 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4577-0216-7 J9 IEEE ENG MED BIO PY 2013 BP 417 EP 420 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BB2DX UT WOS:000341702100101 ER PT S AU Valenza, G Citi, L Lanata, A Scilingo, EP Barbieri, R AF Valenza, Gaetano Citi, Luca Lanata, Antonio Scilingo, Enzo Pasquale Barbieri, Riccardo GP IEEE TI A Nonlinear Heartbeat Dynamics Model Approach for Personalized Emotion Recognition SO 2013 35TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 35th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society (EMBC) CY JUL 03-07, 2013 CL Osaka, JAPAN SP IEEE Engn Med Biol Soc, Japanese Soc Med & Biol Engn ID GAUSSIAN INPUTS AB Emotion recognition based on autonomic nervous system signs is one of the ambitious goals of affective computing. It is well-accepted that standard signal processing techniques require relative long-time series of multivariate records to ensure reliability and robustness of recognition and classification algorithms. In this work, we present a novel methodology able to assess cardiovascular dynamics during short-time (i.e. < 10 seconds) affective stimuli, thus overcoming some of the limitations of current emotion recognition approaches. We developed a personalized, fully parametric probabilistic framework based on point-process theory where heartbeat events are modelled using a 2nd-order nonlinear autoregressive integrative structure in order to achieve effective performances in short-time affective assessment. Experimental results show a comprehensive emotional characterization of 4 subjects undergoing a passive affective elicitation using a sequence of standardized images gathered from the international affective picture system. Each picture was identified by the IAPS arousal and valence scores as well as by a self-reported emotional label associating a subjective positive or negative emotion. Results show a clear classification of two defined levels of arousal, valence and self-emotional state using features coming from the instantaneous spectrum and bispectrum of the considered RR intervals, reaching up to 90% recognition accuracy. C1 [Valenza, Gaetano; Citi, Luca; Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. RP Valenza, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. EM g.valenza@ieee.org; lciti@neurostat.mit.edu; a.lanata@centropiaggio.unipi.it; e.scilingo@centropiaggio.unipi.it; barbieri@neurostat.mit.edu RI Citi, Luca/G-2270-2011; OI Citi, Luca/0000-0001-8702-5654; Barbieri, Riccardo/0000-0001-9381-3833; Lanata, Antonio/0000-0002-6540-5952; Scilingo, Enzo Pasquale/0000-0003-2588-4917; Valenza, Gaetano/0000-0001-6574-1879 FU NIH [R01-HL084502]; EU Commission [ICT-247777] FX The study was supported in part by NIH Grant R01-HL084502 and by the EU Commission under contract ICT-247777 Psyche. NR 19 TC 9 Z9 9 U1 0 U2 4 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4577-0216-7 J9 IEEE ENG MED BIO PY 2013 BP 2579 EP 2582 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BB2DX UT WOS:000341702103009 ER PT S AU Chen, Z Takahashi, K Hatsopoulos, NG AF Chen, Zhe Takahashi, Kazutaka Hatsopoulos, Nicholas G. GP IEEE TI Sparse Bayesian Inference Methods for Decoding 3D Reach and Grasp Kinematics and Joint Angles with Primary Motor Cortical Ensembles SO 2013 35TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 35th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society (EMBC) CY JUL 03-07, 2013 CL Osaka, JAPAN SP IEEE Engn Med Biol Soc, Japanese Soc Med & Biol Engn DE Sparse Bayesian inference; neural decoding; primary motor cortex; reach-to-grasp movement ID LOCAL-FIELD POTENTIALS; CORTEX; SIGNALS; HAND AB Sparse Bayesian inference methods are applied to decode three--dimensional (3D) reach to grasp movement based on recordings of primary motor cortical (M1) ensembles from rhesus macaque. For three linear or nonlinear models tested, variational Bayes (VB) inference in combination with automatic relevance determination (ARD) is used for variable selection to avoid overfitting. The sparse Bayesian linear regression model achieved the overall best performance across objects and target locations. We assessed the sensitivity of M1 units in decoding and evaluated the proximal and distal representations of joint angles in population decoding. Our results suggest that the M1 ensembles recorded from the precentral gyrus area carry more proximal than distal information. C1 [Chen, Zhe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02139 USA. RP Chen, Z (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02139 USA. EM zhechen@mit.edu; kazutaka@uchicago.edu OI Chen, Zhe/0000-0002-6483-6056 FU NIH-NINDS [RO1-NS045853]; Mathematical Biosciences Institute, Ohio State University FX Supported by NIH-NINDS Grant RO1-NS045853 (to N.G.H.) and an Early Career Award from the Mathematical Biosciences Institute, Ohio State University (to Z.C.). K.T. and N.G.H. are with the University of Chicago, Chicago, IL 60637, USA. Z.C. is with the Massachusetts General Hospital/Harvard Medical School and MIT, Cambridge, MA 02139, USA. (Email: zhechen@mit.edu, kazutaka@uchicago.edu) NR 15 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4577-0216-7 J9 IEEE ENG MED BIO PY 2013 BP 5930 EP 5933 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BB2DX UT WOS:000341702106084 ER PT S AU Valenza, G Citi, L Barbieri, R AF Valenza, Gaetano Citi, Luca Barbieri, Riccardo GP IEEE TI Instantaneous Nonlinear Assessment of Complex Cardiovascular Dynamics by Laguerre-Volterra Point Process Models SO 2013 35TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 35th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society (EMBC) CY JUL 03-07, 2013 CL Osaka, JAPAN SP IEEE Engn Med Biol Soc, Japanese Soc Med & Biol Engn ID HEART-RATE-VARIABILITY; SIGNALS AB We report an exemplary study of instantaneous assessment of cardiovascular dynamics performed using point-process nonlinear models based on Laguerre expansion of the linear and nonlinear Wiener-Volterra kernels. As quantifiers, instantaneous measures such as high order spectral features and Lyapunov exponents can be estimated from a quadratic and cubic autoregressive formulation of the model first order moment, respectively. Here, these measures are evaluated on heartbeat series coming from 16 healthy subjects and 14 patients with Congestive Hearth Failure (CHF). Data were gathered from the on-line repository PhysioBank, which has been taken as landmark for testing nonlinear indices. Results show that the proposed nonlinear Laguerre-Volterra point-process methods are able to track the nonlinear and complex cardiovascular dynamics, distinguishing significantly between CHF and healthy heartbeat series. C1 [Valenza, Gaetano; Citi, Luca; Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. RP Citi, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. EM g.valenza@ieee.org; lciti@neurostat.mit.edu; barbieri@neurostat.mit.edu RI Citi, Luca/G-2270-2011; OI Citi, Luca/0000-0001-8702-5654; Barbieri, Riccardo/0000-0001-9381-3833; Valenza, Gaetano/0000-0001-6574-1879 NR 11 TC 7 Z9 7 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4577-0216-7 J9 IEEE ENG MED BIO PY 2013 BP 6131 EP 6134 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BB2DX UT WOS:000341702106132 ER PT S AU Prior, FW Fouke, SJ Benzinger, T Boyd, A Chicoine, M Cholleti, S Kelsey, M Keogh, B Kim, L Milchenko, M Politte, DG Tyree, S Weinberger, K Marcus, D AF Prior, Fred W. Fouke, Sarah J. Benzinger, Tammie Boyd, Alicia Chicoine, Michael Cholleti, Sharath Kelsey, Matthew Keogh, Bart Kim, Lauren Milchenko, Mikhail Politte, David G. Tyree, Stephen Weinberger, Kilian Marcus, Daniel GP IEEE TI Predicting a Multi-Parametric Probability Map of Active Tumor Extent Using Random Forests SO 2013 35TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 35th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society (EMBC) CY JUL 03-07, 2013 CL Osaka, JAPAN SP IEEE Engn Med Biol Soc, Japanese Soc Med & Biol Engn ID GLIOBLASTOMA AB Glioblastoma Mulitforme is highly infiltrative, making precise delineation of tumor margin difficult. Multi-modality or multi-parametric MR imaging sequences promise an advantage over anatomic sequences such as post contrast enhancement as methods for determining the spatial extent of tumor involvement. In considering multi-parametric imaging sequences however, manual image segmentation and classification is time-consuming and prone to error. As a preliminary step toward integration of multi-parametric imaging into clinical assessments of primary brain tumors, we propose a machine-learning based multi-parametric approach that uses radiologist generated labels to train a classifier that is able to classify tissue on a voxel-wise basis and automatically generate a tumor segmentation. A random forests classifier was trained using a leave-one-out experimental paradigm. A simple linear classifier was also trained for comparison. The random forests classifier accurately predicted radiologist generated segmentations and tumor extent. C1 [Prior, Fred W.; Benzinger, Tammie; Boyd, Alicia; Kelsey, Matthew; Milchenko, Mikhail; Politte, David G.; Marcus, Daniel] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. [Fouke, Sarah J.; Keogh, Bart] Swedish Med Ctr, Dept Neurosurg, Seattle, WA 98122 USA. [Cholleti, Sharath] Emory Univ, Ctr Comprehensive Informat, Atlanta, GA 30322 USA. [Kim, Lauren] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Prior, FW (reprint author), Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. EM priorf@mir.wustl.edu; Sarah.Fouke@swedish.org; benzingert@mir.wustl.edu; boyda@mir.wustl.edu; chicoinem@wudosis.wust.edu; sharath.cholleti@emory.edu; kelseym@mir.wustl.edu; Bart.Keogh@swedish.org; LKIM6@partners.org; milchenkom@mir.wustl.edu; politted@mir.wustl.edu; swtyree@wustl.edu; kilian@seas.wustl.edu; dmarcus@wustl.edu FU NIH [1R01NS066905-01] FX Research supported in part by NIH grant 1R01NS066905-01. Data was provided by clinical trial NCT01124461. NR 16 TC 1 Z9 1 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4577-0216-7 J9 IEEE ENG MED BIO PY 2013 BP 6478 EP 6481 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BB2DX UT WOS:000341702106216 ER PT S AU Westover, MB Ching, SN Shafi, MM Cash, SS Brown, EN AF Westover, M. Brandon Ching, ShiNung Shafi, Mouhsin M. Cash, Sydney S. Brown, Emery N. GP IEEE TI Real-Time Segmentation and Tracking of Brain Metabolic State in ICU EEG Recordings of Burst Suppression SO 2013 35TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC) SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT 35th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society (EMBC) CY JUL 03-07, 2013 CL Osaka, JAPAN SP IEEE Engn Med Biol Soc, Japanese Soc Med & Biol Engn ID ELECTROENCEPHALOGRAM AB We provide a method for estimating brain metabolic state based on a reduced-order model of EEG burst suppression. The model, derived from previously suggested biophysical mechanisms of burst suppression, describes important electrophysiological features and provides a direct link to cerebral metabolic rate. We design and fit the estimation method from EEG recordings of burst suppression from a neurological intensive care unit and test it on real and synthetic data. C1 [Westover, M. Brandon; Shafi, Mouhsin M.; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Westover, MB (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. FU NIH [DP1-OD003646] FX This work has been supported by NIH DP1-OD003646 (to ENB). SC holds a Career Award at the Scientific Interface from the Burroughs Wellcome Fund. NR 13 TC 4 Z9 4 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4577-0216-7 J9 IEEE ENG MED BIO PY 2013 BP 7108 EP 7111 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BB2DX UT WOS:000341702107123 ER PT J AU Kang, W Wu, PL Rahmaniheris, M Sha, L Berlin, RB Goldman, JM AF Kang, Woochul Wu, PoLiang Rahmaniheris, Maryam Sha, Lui Berlin, Richard B., Jr. Goldman, Julian M. BE Rodrigues, PP Pechenizkiy, M Gama, J Correia, RC Liu, J Traina, A Lucas, P Soda, P TI Towards Organ-Centric Compositional Development of Safe Networked Supervisory Medical Systems SO 2013 IEEE 26TH INTERNATIONAL SYMPOSIUM ON COMPUTER-BASED MEDICAL SYSTEMS (CBMS) LA English DT Proceedings Paper CT 26th IEEE International Symposium on Computer-Based Medical Systems (CBMS) CY JUN 20-22, 2013 CL Univ Porto, Porto, PORTUGAL SP IEEE, Univ Porto, Fac Med, IEEE, Comp Soc, IEEE, Portugal Sect HO Univ Porto AB Medical devices are increasingly capable of interacting with each other by leveraging network connectivity and interoperability, promising a great benefit for patient safety and effectiveness of medical services. However ad-hoc integration of medical devices through networking can significantly increase the complexity of the system and make the system more vulnerable to potential errors and safety hazards. In this paper we address this problem and introduce an organ-centric compositional development approach. In our approach, medical devices are composed into semi-autonomous clusters according to organ-specific physiology in a network-fail-safe manner Each organcentric cluster captures common device interaction patterns of sensing and control to support human physiology. The library of these formally verified organ-centric architectural patterns enables rapid and safe composition of supervisory controllers, which are specialized for specific medical scenarios. Using airway-laser surgery as a case study of practical importance, we demonstrate the feasibility of our approach under Simulink's model-driven development framework. C1 [Kang, Woochul; Wu, PoLiang; Rahmaniheris, Maryam; Sha, Lui] Univ Illinois, Dept Comp Sci, Chicago, IL 60680 USA. [Berlin, Richard B., Jr.] Carle Fdn Hosp, Urbana, IL 61801 USA. [Goldman, Julian M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Goldman, Julian M.] CIMIT, Cambridge, MA USA. RP Kang, W (reprint author), Univ Illinois, Dept Comp Sci, Chicago, IL 60680 USA. EM woochul@illinois.edu; wu87@illinois.edu; rahmani@illinois.edu; lrs@illinois.edu; Richard.Berlin@carle.com; jgoldman@partners.org NR 11 TC 2 Z9 2 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4799-1053-3 PY 2013 BP 143 EP 148 PG 6 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BB2BB UT WOS:000341591900024 ER PT J AU Clancy, CM AF Clancy, Carolyn M. TI Creating a Healing Environment SO HERD-HEALTH ENVIRONMENTS RESEARCH & DESIGN JOURNAL LA English DT Editorial Material ID DESIGN RP Clancy, CM (reprint author), US Dept Vet Affairs, Washington, DC 20420 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU VENDOME GROUP LLC PI NEW YORK PA 6 EAST 32 ST, 8 FLOOR, NEW YORK, NY 10016 USA SN 1937-5867 EI 2167-5112 J9 HERD-HEALTH ENV RES JI Herd-Health Env. Res. Des. J. PY 2013 VL 7 SU S SI SI BP 5 EP 7 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AN9MP UT WOS:000340931300001 ER PT S AU Slight, SP Nanji, KC Seger, DL Cho, I Volk, LA Bates, DW AF Slight, Sarah P. Nanji, Karen C. Seger, Diane L. Cho, Insook Volk, Lynn A. Bates, David W. BE Lehmann, CU Ammenwerth, E Nohr, C TI Overrides of Clinical Decision Support Alerts in Primary Care Clinics SO MEDINFO 2013: PROCEEDINGS OF THE 14TH WORLD CONGRESS ON MEDICAL AND HEALTH INFORMATICS, PTS 1 AND 2 SE Studies in Health Technology and Informatics LA English DT Proceedings Paper CT 14th World Congress on Medical and Health Informatics (MEDINFO) CY AUG 20-23, 2013 CL Copenhagen, DENMARK DE Clinical decision support systems; electronic prescribing; decision-making; primary health care AB Clinical Decision Support (CDS) systems can alert physicians about potential clinical risks and suggest suitable treatment alternatives at appropriate times in the health care process. We evaluated the frequency with which physicians overrode medication alerts and the override reasons provided. Data obtained from primary care practices affiliated with two Harvard teaching hospitals were downloaded. Physicians overrode more than half of CDS medication alerts, with formulary, age-based, and renal substitutions the most likely. Many drug-drug and drug-allergy interactions overridden had the potential to cause patient harm. C1 [Slight, Sarah P.; Cho, Insook; Bates, David W.] Brigham & Womens Hosp, Div Gen Internal Med, 75 Francis St, Boston, MA 02115 USA. [Slight, Sarah P.; Nanji, Karen C.; Cho, Insook; Bates, David W.] Harvard Med Sch, Boston, MA 02115 USA. [Slight, Sarah P.] Univ Nottingham, Div Primary Care, Nottingham, England. [Nanji, Karen C.] Massachusetts Gen Hosp, Dept Anesthesia, Crit Care & Pain Med, Boston, MA 02114 USA. [Nanji, Karen C.; Seger, Diane L.; Volk, Lynn A.; Bates, David W.] Partners Hlth Syst Inc, Wellesley, MA 02199 USA. RP Slight, SP (reprint author), Brigham & Womens Hosp, Div Gen Internal Med, 75 Francis St, Boston, MA 02115 USA. EM sslight@partners.org NR 2 TC 3 Z9 3 U1 2 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 978-1-61499-289-9; 978-1-61499-288-2 J9 STUD HEALTH TECHNOL PY 2013 VL 192 BP 923 EP 923 DI 10.3233/978-1-61499-289-9-923 PG 1 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA BB1DZ UT WOS:000341021700191 PM 23920697 ER PT S AU Cho, I Slight, SP Nanji, KC Seger, DL Dykes, P Bates, DW AF Cho, Insook Slight, Sarah P. Nanji, Karen C. Seger, Diane L. Dykes, Patricia Bates, David W. BE Lehmann, CU Ammenwerth, E Nohr, C TI Understanding Responses to a Renal Dosing Decision Support System in Primary Care SO MEDINFO 2013: PROCEEDINGS OF THE 14TH WORLD CONGRESS ON MEDICAL AND HEALTH INFORMATICS, PTS 1 AND 2 SE Studies in Health Technology and Informatics LA English DT Proceedings Paper CT 14th World Congress on Medical and Health Informatics (MEDINFO) CY AUG 20-23, 2013 CL Copenhagen, DENMARK DE Clinical decision support systems; electronic prescribing; renal dosing; primary health care AB Renal dosing clinical decision support (CDS) systems have demonstrated clinical effectiveness and potential benefits for patient outcomes. However, the high override rates consistently reported are problematic and undesirable. To understand providers' use patterns of renal dosing CDS, we investigated the override reasons obtained from primary care practices affiliated with two teaching hospitals. We selected a stratified random sample of 300 alerts and reviewed electronic medical records. Appropriateness criteria and an inter-rater reliability process were used. We found that two thirds of alerts were overridden inappropriately, and this proportion was similar for frequent over-riders as compared to the remainder of physicians. These findings imply that strategies are needed to convince providers to accept more clinically appropriate suggestions, though they need to be broadly targeted. C1 [Cho, Insook] Inha Univ, Dept Nursing, Inchon, South Korea. [Cho, Insook; Slight, Sarah P.; Dykes, Patricia; Bates, David W.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA USA. [Slight, Sarah P.; Dykes, Patricia] Univ Nottingham, Div Primary Care, Nottingham, England. [Cho, Insook; Slight, Sarah P.; Nanji, Karen C.; Bates, David W.] Harvard Medical Sch, Boston, MA USA. [Nanji, Karen C.] Massachusetts Gen Hosp, Dept Anesthesia, Critical Care & Pain Med, Boston, MA USA. [Nanji, Karen C.; Seger, Diane L.; Bates, David W.] Partners Healthcare Syst Inc, Wellesley, MA USA. RP Cho, I (reprint author), Inha Univ, Dept Nursing, Inchon, South Korea. NR 2 TC 4 Z9 4 U1 1 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 978-1-61499-289-9; 978-1-61499-288-2 J9 STUD HEALTH TECHNOL PY 2013 VL 192 BP 931 EP 931 DI 10.3233/978-1-61499-289-9-931 PG 1 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA BB1DZ UT WOS:000341021700199 PM 23920705 ER PT S AU Al-Ali, R Reti, S Feldman, H Safran, C Niaz, R Erskine, A Elmagarmid, A Al-Musleh, A AF Al-Ali, Rashid Reti, Shane Feldman, Henry Safran, Charles Niaz, Rashid Erskine, Alistair Elmagarmid, Ahmed Al-Musleh, Abdulwahab BE Lehmann, CU Ammenwerth, E Nohr, C TI Hospital Information System Survey in Qatar SO MEDINFO 2013: PROCEEDINGS OF THE 14TH WORLD CONGRESS ON MEDICAL AND HEALTH INFORMATICS, PTS 1 AND 2 SE Studies in Health Technology and Informatics LA English DT Proceedings Paper CT 14th World Congress on Medical and Health Informatics (MEDINFO) CY AUG 20-23, 2013 CL Copenhagen, DENMARK DE Hospital Information Systems (HIS); Electronic Health Records (EHR) AB Healthcare can be enhanced by the effective use of information technology to improve the quality and safety of care and many healthcare providers are adopting advanced health information technology to improve their healthcare delivery process. Qatar is a relatively young Middle Eastern country with an ambitious and progressive national strategy to develop its healthcare system, including an advanced e-health infrastructure delivering the right medical information at the right time to clinicians and patients. To assess the effectiveness of such programs, it is important to have a pre-intervention baseline from which comparisons, performance against target measures and forward thinking strategic planning can be grounded. This study presents the first published campus wide survey of Hospital Information Systems in large public and private hospitals in Qatar. Objective: To qualitatively assess and describe the current state of Hospital Information Systems in large hospitals in Qatar, and to establish a baseline or reference point for Qatar's readiness for, and adoption of Hospital Information Systems. C1 [Al-Ali, Rashid; Niaz, Rashid; Erskine, Alistair] Sidra Med & Res Ctr, Doha, Qatar. [Reti, Shane; Feldman, Henry; Safran, Charles] BIDMC, Harvard Med Fac Phys, Div Clin Informat, Boston, MA USA. [Al-Musleh, Abdulwahab] Hamad Med Corp, Doha, Qatar. [Elmagarmid, Ahmed] Qatar Comp Res Inst, Al Rayyan, Qatar. RP Al-Ali, R (reprint author), Sidra Med & Res Ctr, Doha, Qatar. NR 2 TC 0 Z9 0 U1 0 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 978-1-61499-289-9; 978-1-61499-288-2 J9 STUD HEALTH TECHNOL PY 2013 VL 192 BP 959 EP 959 DI 10.3233/978-1-61499-289-9-959 PG 1 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA BB1DZ UT WOS:000341021700227 PM 23920733 ER PT B AU David, SA Megginson, D Congleton, C AF David, Susan A. Megginson, David Congleton, Christina BE David, S Clutterbuck, D Megginson, D TI Researching Goals in Coaching SO BEYOND GOALS: EFFECTIVE STRATEGIES FOR COACHING AND MENTORING LA English DT Article; Book Chapter ID AGENDA C1 [David, Susan A.] Harvard Univ, Inst Coaching, McLean Hosp, Sch Med, Cambridge, MA 02138 USA. [David, Susan A.] Harvard Univ, Cambridge, MA 02138 USA. [David, Susan A.] Inst Coachings Res Forum, Thessaloniki, Greece. [Megginson, David] EMCC, Dublin, Ireland. [Megginson, David] Sheffield Business Sch, Sheffield, S Yorkshire, England. [Congleton, Christina] Massachusetts Gen Hosp, Neuroimaging Labs, Boston, MA 02114 USA. RP David, SA (reprint author), Harvard Univ, Inst Coaching, McLean Hosp, Sch Med, Cambridge, MA 02138 USA. NR 24 TC 0 Z9 0 U1 1 U2 1 PU GOWER PUBL CO PI NEW YORK PA 1185 AVE OF THE AMERICAS, NEW YORK, NY 10036 USA BN 978-1-4094-1852-8; 978-1-4094-1851-1 PY 2013 BP 37 EP 54 PG 18 WC Psychology, Applied; Management SC Psychology; Business & Economics GA BA8IS UT WOS:000338188500005 ER PT B AU Kegan, R Congleton, C David, SA AF Kegan, Robert Congleton, Christina David, Susan A. BE David, S Clutterbuck, D Megginson, D TI The Goals Behind the Goals: Pursuing Adult Development in the Coaching Enterprise SO BEYOND GOALS: EFFECTIVE STRATEGIES FOR COACHING AND MENTORING LA English DT Article; Book Chapter AB This chapter is based on an interview with Robert Kegan, the William and Miriam Meehan Professor in Adult Learning and Professional Development at the Harvard University Graduate School of Education. With Lisa Lahey, he is also the co-founder of Minds at Work, a consulting firm that helps individuals, teams, and organizations undergo learning and change. Dr Kegan is the author of numerous books, including The Evolving Self, In Over Our Heads, and (with Lisa Lahey) Immunity to Change. His work on development in adulthood is widely used in education, management, coaching, and organizational learning. C1 [Kegan, Robert] Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA. [Congleton, Christina] Massachusetts Gen Hosp, Neuroimaging Labs, Boston, MA 02114 USA. [David, Susan A.] Harvard Univ, Inst Coaching, McLean Hosp, Sch Med, Cambridge, MA 02138 USA. [David, Susan A.] Harvard Univ, Cambridge, MA 02138 USA. [David, Susan A.] Inst Coachings Res Forum, Woodbury, NY USA. RP Kegan, R (reprint author), Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA. NR 2 TC 0 Z9 0 U1 2 U2 3 PU GOWER PUBL CO PI NEW YORK PA 1185 AVE OF THE AMERICAS, NEW YORK, NY 10036 USA BN 978-1-4094-1852-8; 978-1-4094-1851-1 PY 2013 BP 229 EP 243 PG 15 WC Psychology, Applied; Management SC Psychology; Business & Economics GA BA8IS UT WOS:000338188500013 ER PT S AU Wasterlain, CG Gloss, DS Niquet, J Wasterlain, AS AF Wasterlain, Claude G. Gloss, David S. Niquet, Jerome Wasterlain, Amy S. BE Dulac, O Lassonde, M Sarnat, HB TI Epileptogenesis in the developing brain SO PEDIATRIC NEUROLOGY, PT I SE Handbook of Clinical Neurology LA English DT Article; Book Chapter ID DEVELOPING RAT-BRAIN; TEMPORAL-LOBE EPILEPSY; DELAYED NEURONAL DEATH; EARLY-LIFE SEIZURES; INFLAMMATORY CELL RESPONSE; PROLONGED FEBRILE SEIZURES; INDUCED STATUS EPILEPTICUS; LONG-TERM CONSEQUENCES; ANTIEPILEPTIC DRUGS; IMMATURE BRAIN C1 [Wasterlain, Claude G.; Gloss, David S.; Niquet, Jerome; Wasterlain, Amy S.] VA Greater Los Angeles Hlth Care Syst, Dept Neurol, Los Angeles, CA USA. [Wasterlain, Claude G.; Gloss, David S.; Niquet, Jerome; Wasterlain, Amy S.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Wasterlain, CG (reprint author), West LA VA Med Ctr 127, Dept Neurol, 11301 Wilshire Blvd, West Los Angeles, CA 90073 USA. EM wasterla@ucla.edu FU BLRD VA [I01 BX000273]; NINDS NIH HHS [NS059704, NS13515, U01 NS074926] NR 125 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0072-9752 BN 978-0-444-62698-1; 978-0-444-52891-9 J9 HAND CLINIC PY 2013 VL 111 BP 427 EP 439 PG 13 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA BA6KF UT WOS:000337167000048 PM 23622191 ER PT S AU Gallagher, A Jambaque, I Lassonde, M AF Gallagher, Anne Jambaque, Isabelle Lassonde, Maryse BE Dulac, O Lassonde, M Sarnat, HB TI Cognitive outcome of surgery SO PEDIATRIC NEUROLOGY, PT I SE Handbook of Clinical Neurology LA English DT Article; Book Chapter ID TEMPORAL-LOBE EPILEPSY; CORPUS CALLOSOTOMY; HEMISPHERECTOMIZED PATIENTS; CHILDREN; LOBECTOMY; MEMORY; LANGUAGE; CALLOSUM; ABSENCE C1 [Gallagher, Anne] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Gallagher, Anne] Massachusetts Gen Hosp, Carol & James Herscot Ctr Tuberous Sclerosis Comp, Boston, MA 02114 USA. [Jambaque, Isabelle] INSERM, U663, Paris, France. [Jambaque, Isabelle] Univ Paris 05, Inst Psychol, Paris, France. [Lassonde, Maryse] Univ Montreal, Dept Psychol, Montreal, PQ H2V 2S9, Canada. RP Lassonde, M (reprint author), Univ Montreal, Dept Psychol, 90 Ave Vincent dIndy, Montreal, PQ H2V 2S9, Canada. EM maryse.lassonde@umontreal.ca NR 37 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0072-9752 BN 978-0-444-62698-1; 978-0-444-52891-9 J9 HAND CLINIC PY 2013 VL 111 BP 797 EP 802 PG 6 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA BA6KF UT WOS:000337167000084 PM 23622227 ER PT J AU Nguyen, J Noc, M Nguyen, TN Wang, LF Ngo, HM Cheem, TH Gibson, M AF Nguyen, James Noc, Marko Nguyen, Thach N. Wang, Lefeng Ngo, Hung M. Tan Huay Cheem Gibson, Michael BE Nguyen, T Hu, D Chen, SL Kim, MH Saito, S Grines, C Gibson, CM Bailey, SR TI Acute ST-segment Elevation Myocardial Infarction SO PRACTICAL HANDBOOK OF ADVANCED INTERVENTIONAL CARDIOLOGY, 4TH EDITION LA English DT Article; Book Chapter ID PERCUTANEOUS CORONARY INTERVENTION; ARTERY DISSECTION; PATIENT; REPERFUSION; ANGIOPLASTY; MANAGEMENT; OCCLUSION; ERA C1 [Nguyen, James] Univ Arizona, Med Ctr, Tucson, AZ 85721 USA. [Noc, Marko] Univ Indianapolis, Indianapolis, IN 46227 USA. [Noc, Marko] Univ Med Ctr, Ctr Intens Internal Med, Zaloska Ljubljana, Slovenia. [Nguyen, Thach N.] Journal Intervent Cardiol, Hoboken, NJ USA. [Nguyen, Thach N.] Chinese Med Journal, Beijing, Peoples R China. [Nguyen, Thach N.] Hanoi Med Univ, Hanoi, Vietnam. [Nguyen, Thach N.] Capital Univ Med Sci, Beijing, Peoples R China. [Nguyen, Thach N.] Chinese Peoples Liberat Army, Inst Geriatr Cardiol, Gen Hosp 301, Beijing, Peoples R China. [Nguyen, Thach N.] Friendship Hosp, Beijing, Peoples R China. [Nguyen, Thach N.] Indiana Univ, Indianapolis, IN 46204 USA. [Nguyen, Thach N.] St Mary Hosp, Hobart, IN USA. [Wang, Lefeng] Capital Med Univ, Beijing Chaoyang Hosp, Ctr Heart, Beijing, Peoples R China. [Wang, Lefeng] Capital Med Univ, Beijing Chaoyang Hosp, Cardiac Catheter Lab, Beijing, Peoples R China. [Ngo, Hung M.] Cho Ray Hosp, Dept Intervent Cardiol, Ho Chi Minh City, Vietnam. [Tan Huay Cheem] Singapore Natl Hosp, Singapore, Singapore. [Gibson, Michael] TIMI Data Coordinating Ctr, Boston, MA USA. [Gibson, Michael] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Gibson, Michael] Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. RP Nguyen, J (reprint author), Univ Arizona, Med Ctr, Tucson, AZ 85721 USA. NR 24 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-67047-7 PY 2013 BP 269 EP 292 PG 24 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BA7XW UT WOS:000337892400013 ER PT B AU David, SA Clutterbuck, D Megginson, D Congleton, C AF David, Susan A. Clutterbuck, David Megginson, David Congleton, Christina BE David, S Clutterbuck, D Megginson, D TI Goals: A Long-term View SO BEYOND GOALS: EFFECTIVE STRATEGIES FOR COACHING AND MENTORING LA English DT Article; Book Chapter ID IMPLEMENTATION INTENTIONS; TASK MOTIVATION; GONE WILD; ACHIEVEMENT; PERFORMANCE; BEHAVIOR C1 [David, Susan A.] Harvard Univ, Inst Coaching, McLean Hosp, Sch Med, Cambridge, MA 02138 USA. [David, Susan A.] Harvard Univ, Cambridge, MA 02138 USA. [David, Susan A.] Inst Coachings Res Forum, Thessaloniki, Greece. [Clutterbuck, David; Megginson, David] EMCC, Dublin, Ireland. [Clutterbuck, David] Standard Chartered Bank, London, England. [Clutterbuck, David] Goldman Sachs, New York, NY USA. [Clutterbuck, David] Lloyds TSB, London, England. [Clutterbuck, David] World Bank, Washington, DC USA. [Clutterbuck, David] Nokia, Espoo, Finland. [Clutterbuck, David] Audit Commiss, London, England. [Megginson, David] Sheffield Business Sch, Sheffield, S Yorkshire, England. [Congleton, Christina] Massachusetts Gen Hosp, Neuroimaging Labs, Boston, MA 02114 USA. RP David, SA (reprint author), Harvard Univ, Inst Coaching, McLean Hosp, Sch Med, Cambridge, MA 02138 USA. NR 60 TC 0 Z9 0 U1 0 U2 0 PU GOWER PUBL CO PI NEW YORK PA 1185 AVE OF THE AMERICAS, NEW YORK, NY 10036 USA BN 978-1-4094-1852-8; 978-1-4094-1851-1 PY 2013 BP 1 EP 20 PG 20 WC Psychology, Applied; Management SC Psychology; Business & Economics GA BA8IS UT WOS:000338188500003 ER PT B AU Kram, KE David, SA Congleton, C AF Kram, Kathy E. David, Susan A. Congleton, Christina BE David, S Clutterbuck, D Megginson, D TI Goals in Mentoring Relationships and Developmental Networks SO BEYOND GOALS: EFFECTIVE STRATEGIES FOR COACHING AND MENTORING LA English DT Article; Book Chapter ID CAREERS C1 [Kram, Kathy E.] Boston Univ, Sch Management, Boston, MA 02215 USA. [David, Susan A.] Harvard Univ, McLean Hosp, Inst Coaching, Sch Med, Cambridge, MA 02138 USA. [David, Susan A.] Harvard Univ, Cambridge, MA 02138 USA. [David, Susan A.] Inst Coachings Res Forum, Woodbury, NY USA. [Congleton, Christina] Massachusetts Gen Hosp, Neuroimaging Labs, Boston, MA 02114 USA. RP Kram, KE (reprint author), Boston Univ, Sch Management, Boston, MA 02215 USA. NR 10 TC 0 Z9 0 U1 4 U2 5 PU GOWER PUBL CO PI NEW YORK PA 1185 AVE OF THE AMERICAS, NEW YORK, NY 10036 USA BN 978-1-4094-1852-8; 978-1-4094-1851-1 PY 2013 BP 261 EP 274 PG 14 WC Psychology, Applied; Management SC Psychology; Business & Economics GA BA8IS UT WOS:000338188500015 ER PT J AU Baumgarth, N Carroll, MC Gonzalez, S AF Baumgarth, Nicole Carroll, Michael C. Gonzalez, Santiago BE Webster, RG Monto, AS Braciale, TJ Lamb, RA TI Antibody-mediated immunity SO TEXTBOOK OF INFLUENZA, 2ND EDITION LA English DT Article; Book Chapter ID INFLUENZA-VIRUS INFECTION; B-CELL MEMORY; SECRETING CELLS; ANTIGENIC STRUCTURE; RESPIRATORY-TRACT; HUMORAL IMMUNITY; DENDRITIC CELLS; IGA DEFICIENCY; LYMPH-NODES; MICE C1 [Baumgarth, Nicole] Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA. [Baumgarth, Nicole] Univ Calif Davis, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA. [Carroll, Michael C.; Gonzalez, Santiago] Harvard Univ, Sch Med, Dept Pediat, Program Cellular & Mol Med,Immune Dis Inst, Boston, MA 02115 USA. RP Baumgarth, N (reprint author), Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA. NR 56 TC 2 Z9 2 U1 1 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-63684-8 PY 2013 BP 283 EP 297 D2 10.1002/9781118636817 PG 15 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA BA5CQ UT WOS:000336536600020 ER PT S AU Meyerhoff, DJ Durazzo, TC Ende, G AF Meyerhoff, Dieter J. Durazzo, Timothy C. Ende, Gabriele BE Sommer, WH Spanagel, R TI Chronic Alcohol Consumption, Abstinence and Relapse: Brain Proton Magnetic Resonance Spectroscopy Studies in Animals and Humans SO BEHAVIORAL NEUROBIOLOGY OF ALCOHOL ADDICTION SE Current Topics in Behavioral Neurosciences LA English DT Article; Book Chapter DE Alcoholism; Alcohol use disorders; Magnetic resonance spectroscopy; Neuroimaging; Brain metabolites; Recovery; Relapse; Nicotine; Smoking ID CHRONIC CIGARETTE-SMOKING; GAMMA-AMINOBUTYRIC-ACID; N-ACETYL-ASPARTATE; DSM-IV ALCOHOL; NATIONAL EPIDEMIOLOGIC SURVEY; CORTICAL GABA LEVELS; SHORT-TERM RECOVERY; IN-VIVO; RAT-BRAIN; MR SPECTROSCOPY AB This chapter summarizes the peer-reviewed literature of proton magnetic resonance spectroscopy (H-1 MRS) studies on the effects of chronic and excessive alcohol consumption in both the animal and human brain. After a brief summary of the neuropathology of alcohol use disorders (AUD), we describe the primary brain metabolites measured by in vivo H-1 MRS. We then focus on published MRS studies of animal models of alcohol dependence and of treatment-seeking humans with AUD. We also summarize the scant MRS research on the much larger fraction of treatment-naive individuals with AUD and the similarities and discrepancies relative to treatment-seekers. It is exceedingly apparent that premorbid and/or comorbid disorders/conditions, especially chronic smoking, among individuals with AUD contribute to the considerable variability in the pattern and magnitude of neurobiological and neurocognitive abnormalities in AUD. Therefore, we also review studies on the neurobiological consequences of the combined effects of chronic drinking and smoking in AUD. Finally, as AUD is characterized by a chronically relapsing/remitting course over lifetime and identification of those at greatest risk for relapse is important, we review H-1 MRS studies on brain spectroscopic measures that contribute to the prediction of relapse in AUD. We conclude with an overall assessment of the MRS research literature on brain alcohol effects, the role of animal and human studies in understanding the disease, and discuss the need of widely integrative MRS studies of cohorts that include individuals with comorbidies that are reflective of the general population with AUD. C1 [Meyerhoff, Dieter J.; Durazzo, Timothy C.] San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94121 USA. [Meyerhoff, Dieter J.; Durazzo, Timothy C.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Ende, Gabriele] Cent Inst Mental Hlth, Dept Neuroimaging, Mannheim, Germany. RP Meyerhoff, DJ (reprint author), San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94121 USA. EM dieter.meyerhoff@ucsf.edu FU NIAAA NIH HHS [R01 AA10788]; NIDA NIH HHS [K01 DA24136] NR 151 TC 15 Z9 16 U1 1 U2 4 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1866-3370 BN 978-3-642-28720-6; 978-3-642-28719-0 J9 CURR TOP BEHAV NEURO JI Cur. Top. Behav. Neurosci. PY 2013 VL 13 BP 511 EP 540 DI 10.1007/7854_2011_131 D2 10.1007/978-3-642-28720-6 PG 30 WC Substance Abuse; Neurosciences SC Substance Abuse; Neurosciences & Neurology GA BA9NA UT WOS:000339611900018 PM 21688208 ER PT S AU Caviness, V Ebinger, F AF Caviness, V. Ebinger, F. BE Dulac, O Lassonde, M Sarnat, HB TI Headache in pediatric practice SO PEDIATRIC NEUROLOGY, PT II SE Handbook of Clinical Neurology LA English DT Article; Book Chapter ID FAMILIAL HEMIPLEGIC MIGRAINE; QUALITY STANDARDS SUBCOMMITTEE; POSTURAL TACHYCARDIA SYNDROME; CHILD-NEUROLOGY-SOCIETY; ACADEMY-OF-NEUROLOGY; PATENT FORAMEN OVALE; ALTERNATING HEMIPLEGIA; PROPHYLACTIC TREATMENT; CEREBRAL VASOCONSTRICTION; OPHTHALMOPLEGIC MIGRAINE C1 [Caviness, V.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Ebinger, F.] St Vincenz Hosp, Klin Kinder & Jugendmed, Paderborn, Germany. RP Caviness, V (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM caviness@helix.mgh.harvard.edu NR 86 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0072-9752 BN 978-0-444-62699-8; 978-0-444-52910-7 J9 HAND CLINIC PY 2013 VL 112 BP 827 EP 838 PG 12 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA BA6KI UT WOS:000337167400004 PM 23622290 ER PT S AU Bloch, DB Nobre, RA Yang, WH AF Bloch, Donald B. Nobre, Rita A. Yang, Wei-Hong BE Chan, EKL Fritzler, MJ TI GW/P-Bodies and Autoimmune Disease SO TEN YEARS OF PROGRESS IN GW/P BODY RESEARCH SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID PRIMARY BILIARY-CIRRHOSIS; NUCLEAR-LOCALIZATION SEQUENCE; RNA-ASSOCIATED PROTEIN; PROCESSING BODY; AUTOANTIBODIES; IDENTIFICATION; AUTOANTIGEN; POPULATION; TRANSPORT; COMPONENT C1 [Bloch, Donald B.; Nobre, Rita A.; Yang, Wei-Hong] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Bloch, Donald B.; Nobre, Rita A.; Yang, Wei-Hong] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Bloch, Donald B.; Nobre, Rita A.; Yang, Wei-Hong] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol Gen Med Serv, Boston, MA 02114 USA. RP Bloch, DB (reprint author), Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. EM bloch@helix.mgh.harvard.edu NR 31 TC 3 Z9 3 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0065-2598 BN 978-1-4614-5107-5; 978-1-4614-5106-8 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2013 VL 768 BP 61 EP 70 DI 10.1007/978-1-4614-5107-5_5 D2 10.1007/978-1-4614-5107-5 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Genetics & Heredity; Research & Experimental Medicine GA BA8CV UT WOS:000337973800006 PM 23224965 ER PT S AU Lee, S Vasudevan, S AF Lee, Sooncheol Vasudevan, Shobha BE Chan, EKL Fritzler, MJ TI Post-transcriptional Stimulation of Gene Expression by MicroRNAs SO TEN YEARS OF PROGRESS IN GW/P BODY RESEARCH SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID MENTAL-RETARDATION PROTEIN; MESSENGER-RNA DEGRADATION; AU-RICH-ELEMENT; MEDIATED TRANSLATIONAL REPRESSION; C VIRUS-RNA; LIVER-SPECIFIC MICRORNA; CELL-CYCLE CONTROL; X-RELATED PROTEIN; BINDING PROTEIN; MAMMALIAN-CELLS AB MicroRNAs are small noncoding RNA regulatory molecules that control gene expression by guiding associated effector complexes to other RNAs via sequence-specific recognition of target sites. Misregulation of microRNAs leads to a wide range of diseases including cancers, inflammatory and developmental disorders. MicroRNAs were found to mediate deadenylation-dependent decay and translational repression of messages through partially complementary microRNA target sites in the 3'-UTR (untranslated region). A growing series of studies has demonstrated that microRNAs and their associated complexes (microRNPs) elicit alternate functions that enable stimulation of gene expression in addition to their assigned repressive roles. These reports, discussed in this chapter, indicate that microRNA-mediated effects via natural 3' and 5'-UTRs can be selective and controlled, dictated by the RNA sequence context, associated complex, and cellular conditions. Similar to the effects of repression, upregulated gene expression by microRNAs varies from small refinements to significant amplifications in expression. An emerging theme from this literature is that microRNAs have a versatile range of abilities to manipulate post-transcriptional control mechanisms leading to controlled gene expression. These studies reveal new potentials for microRNPs in gene expression control that develop as responses to specific cellular conditions. C1 [Lee, Sooncheol; Vasudevan, Shobha] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. RP Vasudevan, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. EM SLEE91@partners.org; vasudevan.shobha@mgh.harvard.edu NR 184 TC 40 Z9 42 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0065-2598 BN 978-1-4614-5107-5; 978-1-4614-5106-8 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2013 VL 768 BP 97 EP 126 DI 10.1007/978-1-4614-5107-5_7 D2 10.1007/978-1-4614-5107-5 PG 30 WC Biochemistry & Molecular Biology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Genetics & Heredity; Research & Experimental Medicine GA BA8CV UT WOS:000337973800008 PM 23224967 ER PT B AU Ma, QL Yang, FS Frautschy, SA Cole, GM AF Ma, Qiu-Lan Yang, Fusheng Frautschy, Sally A. Cole, Greg M. BE Maruta, H TI PAK1 in Alzheimer's and Huntington's Diseases SO PAKS, RAC/CDC42 (P21)-ACTIVATED KINASES: TOWARDS THE CURE OF CANCER AND OTHER PAK-DEPENDENT DISEASES SE Elsevier Insights LA English DT Article; Book Chapter ID DENDRITIC SPINE MORPHOGENESIS; D-ASPARTATE RECEPTOR; SRC FAMILY KINASES; A-BETA OLIGOMERS; AMYLOID-BETA; MUTANT HUNTINGTIN; IN-VIVO; SYNAPTIC PLASTICITY; ACTIN CYTOSKELETON; MENTAL-RETARDATION C1 [Ma, Qiu-Lan; Yang, Fusheng; Frautschy, Sally A.; Cole, Greg M.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Ma, Qiu-Lan; Yang, Fusheng; Frautschy, Sally A.; Cole, Greg M.] West Angeles Med Ctr, Greater Los Angeles Vet Affairs Healthcare Syst, Geriatr Res & Clin Ctr, Los Angeles, CA USA. RP Ma, QL (reprint author), Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. NR 87 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-407210-7; 978-0-12-407198-8 J9 ELSEV INSIGHT PY 2013 BP 107 EP 124 DI 10.1016/B978-0-12-407198-8.00006-0 PG 18 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA BA4GB UT WOS:000335640300006 ER PT J AU Politte, LC McDougle, CJ AF Politte, Laura C. McDougle, Christopher J. TI Phase II and III drugs for the treatment of fragile X syndrome SO EXPERT OPINION ON ORPHAN DRUGS LA English DT Review DE autism; FMRP; fragile X syndrome; GABA; GABA receptor agonists; glutamate; group 1 metabotropic glutamate receptors; intellectual disability; mGluR2/3 agonists; mGluR5 antagonists; NMDAR partial agonists; oxytocin; synaptic plasticity ID MENTAL-RETARDATION PROTEIN; FOLIC-ACID TREATMENT; SITE PARTIAL AGONIST; SHORT-TERM-MEMORY; FMR1 KO MICE; MOUSE MODEL; DOUBLE-BLIND; METABOTROPIC GLUTAMATE; TREMOR/ATAXIA SYNDROME; MINOCYCLINE TREATMENT AB Introduction: Fragile X syndrome (FXS), the most common inherited form of intellectual disability and autism, is caused by expansion of CGG trinucleotide repeats in FMR1 and marked reduction or absence of the gene product, FMRP. FMRP suppresses synaptic protein synthesis resulting from group 1 metabotropic glutamate receptor (mGluR) activation, a process critical to normal synaptic plasticity. FXS can be characterized as a disorder of synaptic plasticity with physical, cognitive and behavioral manifestations attributable to, at least in part, excessive mGluR activity and downstream effects. Areas covered: This paper reviews the 'mGluR theory' of FXS and the targeted drugs investigated in Phase II and III trials based on this theory of pathogenesis. A literature review was conducted using the PubMed database with search terms 'fragile X syndrome', 'mGluRs', 'pharmacotherapy' and specific drug-related terms. Other resources were identified by review of relevant reference lists and consultation with experts in the field. Expert opinion: While preclinical trials of targeted drugs in animal models of FXS have been encouraging, more studies are needed to determine clinical efficacy in humans. Challenges to clinical trial design and direction for future drug studies, including consideration of NMDA receptor partial agonists and mGluR2/3 agonists, are discussed. C1 [Politte, Laura C.] Massachusetts Gen Hosp, Lexington, MA 02421 USA. [McDougle, Christopher J.] Lurie Ctr Autism, Lexington, MA 02421 USA. RP Politte, LC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Maguire Rd, Lexington, MA 02421 USA. EM lpolitte@partners.org NR 149 TC 0 Z9 0 U1 5 U2 10 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 2167-8707 J9 EXPERT OPIN ORPHAN D JI Exp. Opin. Orphan Drugs PD JAN PY 2013 VL 1 IS 1 BP 47 EP 65 DI 10.1517/21678707.2013.750240 PG 19 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AK1VM UT WOS:000338205800005 ER PT J AU Austin, SB Richmond, TK Spadano-Gasbarro, J Greaney, ML Blood, EA Walls, C Wang, ML Mezgebu, S Osganian, SK Peterson, KE AF Austin, S. Bryn Richmond, Tracy K. Spadano-Gasbarro, Jennifer Greaney, Mary L. Blood, Emily A. Walls, Courtney Wang, Monica L. Mezgebu, Solomon Osganian, Stavroula K. Peterson, Karen E. TI The Contribution of School Environmental Factors to Individual and School Variation in Disordered Weight Control Behaviors in a Statewide Sample of Middle Schools SO EATING DISORDERS LA English DT Article ID BODY-IMAGE CONCERNS; ADOLESCENT GIRLS; EATING-DISORDERS; PEER INFLUENCES; PROJECT EAT; OVERWEIGHT; PREVENTION; CONTEXT; SATISFACTION; STUDENTS AB We investigated the contribution of school environmental factors to individual and school variation in disordered weight control behaviors (DWCB). Analyses were based on self-report data gathered from 18,567 middle-school students in 2005 and publicly available data on school characteristics. We observed large differences across schools in percent of students engaging in DWCB in the past month, ranging from less than 1% of the student body to 12%. School-neighborhood poverty was associated with higher odds of DWCB in boys. Preventive strategies need to account for wide variability across schools and environmental factors that may contribute to DWCB in early adolescence. C1 [Austin, S. Bryn; Richmond, Tracy K.] Boston Childrens Hosp, Div Adolescent & Young Adult Med, Boston, MA 02115 USA. [Austin, S. Bryn; Wang, Monica L.; Peterson, Karen E.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA. [Spadano-Gasbarro, Jennifer; Greaney, Mary L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Greaney, Mary L.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Blood, Emily A.; Walls, Courtney; Osganian, Stavroula K.] Boston Childrens Hosp, Clin Res Program, Boston, MA USA. [Mezgebu, Solomon] Massachusetts Dept Publ Hlth, Boston, MA USA. [Peterson, Karen E.] Univ Michigan, Sch Publ Hlth, Human Nutr Program, Ann Arbor, MI 48109 USA. RP Austin, SB (reprint author), Boston Childrens Hosp, Div Adolescent & Young Adult Med, 300 Longwood Ave, Boston, MA 02115 USA. EM bryn.austin@childrens.harvard.edu FU Ellen Feldberg Gordon Fund for Eating Disorders Research; Massachusetts Department of Public Health; International Nutrition Foundation, Inc.; Centers for Disease Control and Prevention [U58/CCU12282]; Maternal and Child Health Bureau, HRSA [6T71-MC00009] FX This work was supported by the Ellen Feldberg Gordon Fund for Eating Disorders Research and the Massachusetts Department of Public Health in collaboration with the International Nutrition Foundation, Inc. Partial funding for this project was also provided by Cooperative Agreement U58/CCU12282 with the Centers for Disease Control and Prevention. S. B. Austin and T. K. Richmond are supported by the Leadership Education in Adolescent Health Project, Maternal and Child Health Bureau, HRSA grant 6T71-MC00009. The authors would like to thank Maria Bettencourt, Vanessa Cavallero, Christine Horan, Vivian Morris, Lauren Nichols, Christine Nordstrom, and Sylvia Stevens-Edouard for their contributions to the Massachusetts Healthy Choices Study, and the school staff and students who participated in the study. NR 52 TC 3 Z9 3 U1 3 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1064-0266 EI 1532-530X J9 EAT DISORD JI Eat. Disord PY 2013 VL 21 IS 2 BP 91 EP 108 DI 10.1080/10640266.2013.761080 PG 18 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA AJ2PR UT WOS:000337501000001 PM 23421693 ER PT J AU Zhu, AX AF Zhu, Andrew X. TI New agents on the horizon in hepatocellular carcinoma SO THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY LA English DT Review DE bevacizumab; brivanib; EGFR inhibitors; everolimus; hepatocellular carcinoma; linifanib; Met inhibitors; sorafenib; sunitinib; targeted agents ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; FACTOR RECEPTOR; PHASE-II; PROGNOSTIC-SIGNIFICANCE; FACTOR-ALPHA; EXPRESSION; CANCER; MULTICENTER; SUNITINIB AB Despite the successful approval and extensive application of sorafenib, the prognosis for patients with advanced hepatocellular carcinoma (HCC) remains poor. Fortunately, there have been renewed and continued interests and active research in developing other molecularly targeted agents in HCC during the past few years. While there is early evidence of antitumor activity of several agents in phase I/II studies, phase III efforts with a few targeted agents have failed, highlighting the challenges of new drug development in HCC. This review summarizes the current status of other molecularly targeted agents under development in advanced HCC. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02114 USA. RP Zhu, AX (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, 55 Fruit St,LH POB 232, Boston, MA 02114 USA. EM azhu@partners.org NR 49 TC 12 Z9 13 U1 0 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1758-8340 EI 1758-8359 J9 THER ADV MED ONCOL JI Ther. Adv. Med. Oncol. PD JAN PY 2013 VL 5 IS 1 BP 41 EP 50 DI 10.1177/1758834012458480 PG 10 WC Oncology SC Oncology GA AJ4AD UT WOS:000337610300004 PM 23323146 ER PT B AU Polley, DB Seidl, AH Wang, Y Sanchez, JT AF Polley, D. B. Seidl, A. H. Wang, Y. Sanchez, J. T. BE Rubenstein, JLR Rakic, P TI Functional Circuit Development in the Auditory System SO COMPREHENSIVE DEVELOPMENTAL NEUROSCIENCE: NEURAL CIRCUIT DEVELOPMENT AND FUNCTION IN THE HEALTHY AND DISEASED BRAIN LA English DT Article; Book Chapter ID COCHLEAR NUCLEUS; AFFERENT INFLUENCES; ACTION-POTENTIALS; HEARING-LOSS; HAIR-CELLS; CORTICAL DEVELOPMENT; CRITICAL PERIOD; CORTEX; CHICKEN; MAGNOCELLULARIS C1 [Polley, D. B.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Polley, D. B.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Seidl, A. H.; Wang, Y.; Sanchez, J. T.] Univ Washington, Virginia Merrill Bloedel Hearing Res Ctr, Seattle, WA 98195 USA. [Seidl, A. H.; Wang, Y.; Sanchez, J. T.] Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. RP Polley, DB (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. OI Polley, Daniel/0000-0002-5120-2409 NR 42 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-397346-7; 978-0-12-397267-5 PY 2013 BP 21 EP 39 DI 10.1016/B978-0-12-397267-5.00136-9 PG 19 WC Developmental Biology; Clinical Neurology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA BA3CS UT WOS:000334110800003 ER PT S AU Salmi, A Heino, O Nieminen, HJ Salmi, T Karppinen, P Patola, T Haeggstrom, E Hacking, SA AF Salmi, A. Heino, O. Nieminen, H. J. Salmi, T. Karppinen, P. Patola, T. Haeggstrom, E. Hacking, S. A. GP IEEE TI Detecting defects in adhesion between a metal hemisphere and a polymer base SO 2013 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS) SE IEEE International Ultrasonics Symposium LA English DT Proceedings Paper CT IEEE International Ultrasonics Symposium (IUS) CY JUL 21-25, 2013 CL Prague, CZECH REPUBLIC SP IEEE DE ultrasound; hemisphere; guided acoustic waves; adhesion ID GUIDED-WAVES; LAMB WAVES AB Detecting localized defects in adhesion on a spherical shell is challenging, especially if one has access only to its rim. Our group previously quantified the spatial average of the adhesion between a metal hemisphere and a polymer base [1]. Here we report on progress towards determining the presence of localized defects, their position, size, and strength. Tests were performed on a 5 cm diameter metal hemisphere attached to a UHMWPE (Polyethylene, PE RCH 1000 D150x2000 Etralene) base. Defects in adhesion were generated by machining hexagonal holes (5 to 17.5 mm) into the polymer base prior to fixing by adhesive. These known areas without adhesion were remotely characterized with a guided ultrasonic wave (Lamb quasi-modes) generated by a Nd:YAG (1064 nm, 8 ns pulse duration) pulse from one rim of the shell and detected with a laser Doppler vibrometer. We detected the presence and position of the defects. C1 [Salmi, A.; Heino, O.; Nieminen, H. J.; Salmi, T.; Karppinen, P.; Patola, T.; Haeggstrom, E.] Univ Helsinki, Dept Phys, Div Mat Sci, Helsinki, Finland. [Hacking, S. A.] Massachusetts Gen Hosp, Harvard Med Sch, Dept Orthopaed, Boston, MA USA. RP Salmi, A (reprint author), Univ Helsinki, Dept Phys, Div Mat Sci, Helsinki, Finland. EM ari.salmi@helsinki.fi RI Salmi, Ari/B-1317-2009 FU Jenny and Antti Wihuri Foundation FX The authors gratefully acknowledge the help Mr. Joona Eskelinen provided for the measurement of the laser energy. The funding for Dr. Salmi was provided by the Jenny and Antti Wihuri Foundation. NR 8 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1948-5719 BN 978-1-4673-5686-2 J9 IEEE INT ULTRA SYM PY 2013 BP 1692 EP 1695 DI 10.1109/ULTSYM.2013.0179 PG 4 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA BA5IA UT WOS:000336665300430 ER PT B AU MacDonald, JL Fame, RM Azim, E Shnider, SJ Molyneaux, BJ Arlotta, P Macklis, JD AF MacDonald, J. L. Fame, R. M. Azim, E. Shnider, S. J. Molyneaux, B. J. Arlotta, P. Macklis, J. D. BE Rubenstein, JLR Rakic, P TI Specification of Cortical Projection Neurons Transcriptional Mechanisms SO COMPREHENSIVE DEVELOPMENTAL NEUROSCIENCE: PATTERNING AND CELL TYPE SPECIFICATION IN THE DEVELOPING CNS AND PNS LA English DT Article; Book Chapter ID DEVELOPING CEREBRAL-CORTEX; CORTICOSPINAL MOTOR-NEURONS; INTERMEDIATE PROGENITOR CELLS; SUBTYPE-SPECIFIC GENES; CENTRAL-NERVOUS-SYSTEM; UPPER LAYER NEURONS; RADIAL GLIAL-CELLS; DEVELOPING NEOCORTEX; SUBVENTRICULAR ZONE; CORPUS-CALLOSUM C1 [MacDonald, J. L.; Fame, R. M.; Azim, E.; Shnider, S. J.; Molyneaux, B. J.; Arlotta, P.; Macklis, J. D.] Harvard Univ, Cambridge, MA 02138 USA. [MacDonald, J. L.; Fame, R. M.; Azim, E.; Shnider, S. J.; Molyneaux, B. J.; Arlotta, P.; Macklis, J. D.] Harvard Univ, Sch Med, Boston, MA USA. [MacDonald, J. L.; Fame, R. M.; Azim, E.; Shnider, S. J.; Molyneaux, B. J.; Arlotta, P.; Macklis, J. D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP MacDonald, JL (reprint author), Harvard Univ, Cambridge, MA 02138 USA. OI MacDonald, Jessica/0000-0002-9111-5756 NR 212 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-397348-1; 978-0-12-397265-1 PY 2013 BP 475 EP 502 DI 10.1016/B978-0-12-397265-1.00098-8 PG 28 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA BA3AM UT WOS:000334076200026 ER PT J AU Citi, L Micera, S AF Citi, Luca Micera, Silvestro BE Farina, D Jensen, W Akay, M TI WAVELET DENOISING AND CONDITIONING OF NEURAL RECORDINGS SO INTRODUCTION TO NEURAL ENGINEERING FOR MOTOR REHABILITATION LA English DT Article; Book Chapter ID SPIKE DETECTION; SIGNAL; CLASSIFICATION; ALGORITHM AB This chapter presents wavelet-based denoising algorithms as a preprocessing stage before spike detection and sorting. The first part of the chapter is an overview of wavelet-based denoising. The choices that the designer is required to make when implementing a wavelet-based denoising algorithm are presented in detail. In particular, the dyadic wavelet transform is compared with a time-invariant approach, showing that the latter is best suited to the denoising of neural signals. The second part shows a sample application with eletroneurographic (ENG) signals recorded from the sciatic nerve of rabbits while the experimenter stimulated the paw of the animal. A machine learning algorithm is trained to infer the stimulus applied based on the recorded ENG signals. The wavelet-based denoising is compared with a traditional band-pass filter in two cases: when followed by spike sorting and when followed by traditional rectified bin integration (RBI). The results illustrate the benefits of wavelet denoising over standard band-pass filtering and demonstrate that there is an even more marked improvement when the subsequent step requires signals with high signal-to-noise ratio (SNR), such as in the case of spike sorting. C1 [Citi, Luca] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. [Citi, Luca] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Micera, Silvestro] Scuola Super Sant Anna, BioRobot Inst, Pisa, Italy. [Micera, Silvestro] Swiss Fed Inst Technol Lausanne EPFL, Ctr Neuroprosthet, Lausanne, Switzerland. RP Citi, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. NR 18 TC 0 Z9 0 U1 0 U2 2 PU JOHN WILEY & SONS PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER, W SUSSEX PO 19 8SQ, ENGLAND BN 978-0-470-91673-5 PY 2013 BP 173 EP 182 PG 10 WC Engineering, Biomedical; Neurosciences; Rehabilitation SC Engineering; Neurosciences & Neurology; Rehabilitation GA BA2KE UT WOS:000333469200012 ER PT J AU Newmark, JL Ahn, YK Adams, MC Bittner, EA Wilcox, SR AF Newmark, Jordan L. Ahn, Young K. Adams, Mark C. Bittner, Edward A. Wilcox, Susan R. TI Use of Video Laryngoscopy and Camera Phones to Communicate Progression of Laryngeal Edema in Assessing for Extubation: A Case Series SO JOURNAL OF INTENSIVE CARE MEDICINE LA English DT Article DE video laryngoscopy; airway management; extubation criteria; laryngeal edema ID RANDOMIZED CLINICAL-TRIAL; POSTEXTUBATION STRIDOR; AIRWAY-OBSTRUCTION; METAANALYSIS; ADULTS AB Video laryngoscopy has demonstrated utility in airway management. For the present case series, we report the use of video laryngoscopy to evaluate the airway of critically ill, mechanically ventilated patients, as a means to reduce the risk of immediate postextubation stridor by assessing the degree of laryngeal edema. We also describe the use of cellular phone cameras to document and communicate airway edema in using video laryngoscopy for the patients' medical records. We found video laryngoscopy to be an effective method of assessing airway edema, and cellular phone cameras were useful for recording and documenting video laryngoscopy images for patients' medical records. C1 [Newmark, Jordan L.; Ahn, Young K.; Adams, Mark C.; Bittner, Edward A.; Wilcox, Susan R.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Bittner, Edward A.; Wilcox, Susan R.] Harvard Univ, Sch Med, Boston, MA USA. [Wilcox, Susan R.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Wilcox, SR (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,4th Floor, Boston, MA 02114 USA. EM swilcox1@partners.org OI Wilcox, Susan/0000-0001-7477-7531 NR 11 TC 5 Z9 5 U1 1 U2 50 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0885-0666 EI 1525-1489 J9 J INTENSIVE CARE MED JI J. Intensive Care Med. PD JAN-FEB PY 2013 VL 28 IS 1 BP 67 EP 71 DI 10.1177/0885066612437528 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 144OS UT WOS:000318949900007 PM 22337710 ER PT S AU Warren, T Dickey, M AF Warren, T. Dickey, M. BE Hamilton, AC TI The influence of event-related knowledge on verb-argument processing in aphasia SO 51ST ACADEMY OF APHASIA PROCEEDINGS SE Procedia Social and Behavioral Sciences LA English DT Proceedings Paper CT 51st Conference of the Academy-of-Aphasia CY OCT 20-22, 2013 CL Lucerne, SWITZERLAND SP Acad Aphasia C1 [Warren, T.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Dickey, M.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Warren, T (reprint author), Univ Pittsburgh, Pittsburgh, PA 15260 USA. EM mdickey@pitt.edu OI Dickey, Michael Walsh/0000-0002-9068-3313 FU National Institutes of Health [R01DC011520]; [UL1TR000005] FX This research was supported by the National Institutes of Health through Grant number R01DC011520 to the authors and by Grant number UL1TR000005 to the Clinical and Translational Science Institute of the University of Pittsburgh. It is the result of work supported with resources and the use of facilities at the VA Pittsburgh Healthcare System. Thanks are due to Minas Abovyan, Amanda Fryd, Emily Kosenske, Molly Lane, Evelyn Milburn, Hannah Rosenberg, Hyunsoo Yoo, and Lidia Zacharczuk for help running participants, to Alice Proverbio and Federica Riva for sharing their picture stimuli from Proverbio and Riva (2009), and to audiences at the 2012 and 2013 CUNY Sentence Processing Conference and the 2013 Academy of Aphasia meeting for comments and suggestions. Special thanks are due to the adults with aphasia who participated in these studies. A preliminary version of this work was published as Warren and Dickey (2013). NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-0428 J9 PROCD SOC BEHV PY 2013 VL 94 BP 194 EP + DI 10.1016/j.sbspro.2013.09.095 PG 2 WC Psychology, Clinical SC Psychology GA BA4IF UT WOS:000335774400094 ER PT S AU Dickey, M Yoo, H AF Dickey, M. Yoo, H. BE Hamilton, AC TI Acquisition versus generalization in sentence production treatment in aphasia: Dose-response relationships SO 51ST ACADEMY OF APHASIA PROCEEDINGS SE Procedia Social and Behavioral Sciences LA English DT Proceedings Paper CT 51st Conference of the Academy-of-Aphasia CY OCT 20-22, 2013 CL Lucerne, SWITZERLAND SP Acad Aphasia C1 [Dickey, M.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. [Yoo, H.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. RP Dickey, M (reprint author), Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. EM mdickey@pitt.edu OI Dickey, Michael Walsh/0000-0002-9068-3313 NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-0428 J9 PROCD SOC BEHV PY 2013 VL 94 BP 281 EP + DI 10.1016/j.sbspro.2013.09.141 PG 2 WC Psychology, Clinical SC Psychology GA BA4IF UT WOS:000335774400140 ER PT S AU Holers, VM Rohrer, B Tomlinson, S AF Holers, V. Michael Rohrer, Baerbel Tomlinson, Stephen BE Lambris, JD Holers, VM Ricklin, D TI CR2-Mediated Targeting of Complement Inhibitors: Bench-to-Bedside Using a Novel Strategy for Site-Specific Complement Modulation SO COMPLEMENT THERAPEUTICS SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; EPSTEIN-BARR-VIRUS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; PATHWAY-MEDIATED DISEASES; CD21 LIGAND-BINDING; MACULAR DEGENERATION; ALTERNATIVE PATHWAY; REPERFUSION INJURY; FACTOR-H; CHOROIDAL NEOVASCULARIZATION AB Recent approval of the first human complement pathway-directed therapeutics, along with high-pro file genetic association studies, has catalyzed renewed biopharmaceutical interest in developing drugs that modulate the complement system. Substantial challenges remain, however, that must be overcome before widespread application of complement inhibitors in inflammatory and autoimmune diseases becomes possible. Among these challenges are the following: (1) defining the complement pathways and effector mechanisms that cause tissue injury in humans and determining whether the relative importance of each varies by disease, (2) blocking or modulating, using traditional small molecule or biologic approaches, the function of complement proteins whose circulating levels are very high and whose turnover rates are relatively rapid, especially in the setting of acute and chronic autoimmune diseases, and (3) avoiding infectious complications or impairment of other important physiological functions of complement when using systemically active complement-blocking agents. This chapter will review data that address these challenges to therapeutic development, with a focus on the development of a novel strategy of blocking specific complement pathways by targeting inhibitors using a recombinant portion of the human complement receptor type 2 (CR2/CD21) which specifically targets to sites of local complement C3 activation where C3 fragments are covalently fixed. Recently, the first of these CR2-targeted proteins has entered human phase I studies in the human disease paroxysmal nocturnal hemoglobinuria. The results of murine translational studies using CR2-targeted inhibitors strongly suggest that a guiding principle going forward in complement therapeutic development may well be to focus on developing strategies to modulate the pathway as precisely as possible by physically localizing therapeutic inhibitory effects. C1 [Holers, V. Michael] Univ Colorado, Sch Med, Dept Med, Aurora, CO 80045 USA. [Holers, V. Michael] Univ Colorado, Sch Med, Dept Immunol, Aurora, CO USA. [Rohrer, Baerbel] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. [Rohrer, Baerbel; Tomlinson, Stephen] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Tomlinson, Stephen] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. RP Holers, VM (reprint author), Univ Colorado, Sch Med, Dept Med, Aurora, CO 80045 USA. EM michael.holers@ucdenver.edu FU NEI NIH HHS [R01 EY019320]; NHLBI NIH HHS [HL086576, R01 HL082485]; NIAMS NIH HHS [R01 AR51749] NR 106 TC 27 Z9 28 U1 4 U2 10 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0065-2598 BN 978-1-4614-4117-5; 978-1-4614-4118-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2013 VL 735 BP 137 EP 154 DI 10.1007/978-1-4614-4118-2_9 D2 10.1007/978-1-4614-4118-2 PG 18 WC Immunology; Microbiology SC Immunology; Microbiology GA BA2RJ UT WOS:000333837700010 PM 23402024 ER PT S AU Chan, YM AF Chan, Yee-Ming BE Kauffman, AS Smith, JT TI Effects of Kisspeptin on Hormone Secretion in Humans SO KISSPEPTIN SIGNALING IN REPRODUCTIVE BIOLOGY SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID GONADOTROPIN-RELEASING-HORMONE; PROTEIN-COUPLED RECEPTOR; MONKEY MACACA-MULATTA; INTERPULSE INTERVAL SEQUENCE; STRESS-INDUCED SUPPRESSION; MESSENGER-RNA EXPRESSION; LUTEINIZING-HORMONE; HYPOGONADOTROPIC HYPOGONADISM; MENSTRUAL-CYCLE; FEMALE RAT AB Studies of the actions of kisspeptin in human subjects have examined the effects of different kisspeptin isoforms, doses, and routes of administration on LH secretion, a surrogate measure of GnRH release. These studies, in addition to detailing how these different variables affect LH secretion in response to kisspeptin, have produced new insights into kisspeptin physiology: (1) Brief exposure to kisspeptin results in sustained GnRH release lasting similar to 17 min in men. (2) Women in different phases of the menstrual cycle have differences in their response to kisspeptin, suggesting that endogenous kisspeptin secretion and GnRH neuronal responsiveness vary in response to the changing sex-steroid environment across the menstrual cycle. (3) Kisspeptin resets the GnRH pulse generator in men, but does not appear to do so in women. (4) Continuous exposure to kisspeptin results in desensitization to kisspeptin, and thus kisspeptin has the potential to either stimulate or suppress reproductive endocrine activity depending on the mode of administration. These findings pave the way for future studies using kisspeptin as a physiologic, diagnostic, and therapeutic tool in both healthy adults and in patients with reproductive disorders. C1 [Chan, Yee-Ming] Boston Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. [Chan, Yee-Ming] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. [Chan, Yee-Ming] Massachusetts Gen Hosp, Dept Med, Harvard Reprod Sci Ctr, Boston, MA 02114 USA. RP Chan, YM (reprint author), Boston Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. EM ymchan@partners.org NR 68 TC 6 Z9 6 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0065-2598 BN 978-1-4614-6199-9; 978-1-4614-6198-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2013 VL 784 BP 89 EP 112 DI 10.1007/978-1-4614-6199-9_5 D2 10.1007/978-1-4614-6199-9 PG 24 WC Endocrinology & Metabolism; Medicine, Research & Experimental SC Endocrinology & Metabolism; Research & Experimental Medicine GA BA3FX UT WOS:000334207100006 PM 23550003 ER PT S AU Silveira, LG Latronico, AC Seminara, SB AF Silveira, Leticia Gontijo Latronico, Ana Claudia Seminara, Stephanie Beth BE Kauffman, AS Smith, JT TI Kisspeptin and Clinical Disorders SO KISSPEPTIN SIGNALING IN REPRODUCTIVE BIOLOGY SE Advances in Experimental Medicine and Biology LA English DT Article; Book Chapter ID GONADOTROPIN-RELEASING-HORMONE; IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; CENTRAL PRECOCIOUS PUBERTY; REVERSIBLE KALLMANN-SYNDROME; HAMSTERS PHODOPUS-SUNGORUS; MESSENGER-RNA EXPRESSION; AREA BRAIN GRAFTS; NEUROKININ-B; SIBERIAN HAMSTERS; HOMOZYGOUS MUTATION AB The hypothalamic hormone GnRH has traditionally been viewed as a central driver of the hypothalamic-pituitary-gonadal axis. Pulsatile GnRH release is required for pulsatile gonadotropin secretion, which then modulates gonadal steroid feedback and brings about full fertility in the adult. Pathways governing GnRH ontogeny and physiology have been discovered by studying humans with disorders of GnRH secretion. In this chapter, the human genetics of the kisspeptin signaling pathway in patients with diverse reproductive phenotypes will be explored. The discovery of defects in the kisspeptin system in several reproductive disorders has shed light on the mechanisms involved in regulating GnRH secretion, revealing the critical role played by the kisspeptin signaling pathway in pubertal initiation and reproductive function. C1 [Silveira, Leticia Gontijo; Latronico, Ana Claudia] Univ Sao Paulo, Hosp Clin, Div Endocrinol & Metab, Dept Internal Med, Sao Paulo, Brazil. [Seminara, Stephanie Beth] Massachusetts Gen Hosp, Div Endocrine, Reprod Endocrine Unit, Dept Internal Med, Boston, MA 02114 USA. RP Seminara, SB (reprint author), Massachusetts Gen Hosp, Div Endocrine, Reprod Endocrine Unit, Dept Internal Med, Bartlett Hall Extens 504,55 Fruit St, Boston, MA 02114 USA. EM leticia_gontijo@yahoo.com.br; sseminara@partners.org OI Latronico Xavier, Ana Claudia/0000-0001-6782-693X FU NICHD NIH HHS [K24 HD067388, R01 HD043341, U54 HD028138, U54HD028138] NR 75 TC 6 Z9 6 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0065-2598 BN 978-1-4614-6199-9; 978-1-4614-6198-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2013 VL 784 BP 187 EP 199 DI 10.1007/978-1-4614-6199-9_9 D2 10.1007/978-1-4614-6199-9 PG 13 WC Endocrinology & Metabolism; Medicine, Research & Experimental SC Endocrinology & Metabolism; Research & Experimental Medicine GA BA3FX UT WOS:000334207100010 PM 23550007 ER PT J AU Schalock, PC Dunnick, CA Nedorost, S Brod, B Warshaw, E Mowad, C AF Schalock, Peter C. Dunnick, Cory A. Nedorost, Susan Brod, Bruce Warshaw, Erin Mowad, Christen TI American Contact Dermatitis Society Core Allergen Series SO DERMATITIS LA English DT Review ID PATCH TESTS; REPRODUCIBILITY AB Evidence for the effectiveness of patch testing and the need for an expanded series that provides experience and evidence-based suggestions for an extended patch testing series are examined in this review. Many of those testing with shorter allergen series are interested in expanding the spectrum of patch testing. The American Contact Dermatitis Society (ACDS) Core Allergen Series Group has arranged a group of suggested allergen groups that can be logically scaled up or down depending on the needs of the patch tester and the community being tested. This is not an ACDS 80 Standard. We suggest a core group of allergens similar to the TRUE Test (SmartPractice, Phoenix, Ariz) with subsequent trays providing a greater breadth of coverage in a logical fashion, with more likely allergens being higher in the tray. For more extensive testing, specialty trays (ie, cosmetics, metals, plant, etc) are recommended. C1 [Schalock, Peter C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. [Dunnick, Cory A.] Univ Colorado, Dept Dermatol, Denver, CO 80202 USA. [Dunnick, Cory A.] Denver VA Med Ctr, Denver, CO USA. [Nedorost, Susan] Univ Hosp Case Med Ctr, Dept Dermatol, Cleveland, OH USA. [Brod, Bruce] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Warshaw, Erin] Univ Minnesota, Dept Dermatol, Minneapolis, MN 55455 USA. [Mowad, Christen] Geisinger Hlth Syst, Dept Dermatol, Danville, PA USA. RP Schalock, PC (reprint author), Massachusetts Gen Hosp, Dept Dermatol, BAR622,55 Fruit St, Boston, MA 02114 USA. EM schalock.prof@gmail.com OI Schalock, Peter/0000-0001-8953-4639 NR 23 TC 20 Z9 20 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1710-3568 EI 2162-5220 J9 DERMATITIS JI Dermatitis PD JAN-FEB PY 2013 VL 24 IS 1 BP 7 EP 9 DI 10.1097/DER.0b013e318281d87b PG 3 WC Dermatology SC Dermatology GA AG5KQ UT WOS:000335458300002 PM 23340393 ER PT J AU Khodabux, N da Silva, CTB Birmes, P Schmitt, L Bui, E AF Khodabux, N. Belem da Silva, C. Tschiedel Birmes, P. Schmitt, L. Bui, E. TI EXISTENTIAL ANXIETY AND POSTTRAUMATIC STRESS DISORDER SYMPTOMS IN A SAMPLE OF PSYCHIATRIC OUTPATIENTS SO EUROPEAN PSYCHIATRY LA English DT Meeting Abstract C1 [Khodabux, N.] Ctr Hosp Univ Toulouse, Toulouse, France. [Belem da Silva, C. Tschiedel] Univ Fed Rio Grande Sul UFRGS, Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil. [Birmes, P.] Hop Casselardit, Lab Stress Traumat, Toulouse, France. [Schmitt, L.] Hop Casselardit, Ctr Hosp Univ Toulouse, Toulouse, France. [Bui, E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Anxiety & Traumat Stress Disorders, Boston, MA USA. RI Bui, Eric/J-8347-2015 OI Bui, Eric/0000-0002-1413-6473 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 EI 1778-3585 J9 EUR PSYCHIAT JI Eur. Psychiat. PY 2013 VL 28 SU 1 MA 915 PG 1 WC Psychiatry SC Psychiatry GA AG5LN UT WOS:000335460600361 ER PT J AU Tapp, A Wood, A Sylvers, P Kilzieh, N Saxon, A AF Tapp, A. Wood, A. Sylvers, P. Kilzieh, N. Saxon, A. TI QUETIAPINE FOR THE TREATMENT OF COCAINE DEPENDENCE SO EUROPEAN PSYCHIATRY LA English DT Meeting Abstract C1 [Tapp, A.; Wood, A.; Sylvers, P.; Kilzieh, N.] VA Puget Sound Hlth Care Syst, Psychiat, Tacoma, WA USA. [Saxon, A.] VA Puget Sound Hlth Care Syst, Psychiat, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 EI 1778-3585 J9 EUR PSYCHIAT JI Eur. Psychiat. PY 2013 VL 28 SU 1 MA 2733 PG 1 WC Psychiatry SC Psychiatry GA AG5LN UT WOS:000335460602138 ER PT J AU Taylor, PN Baier, G Cash, SS Dauwels, J Slotine, JJ Wang, YJ AF Taylor, Peter N. Baier, Gerold Cash, Sydney S. Dauwels, Justin Slotine, Jean-Jacques Wang, Yujiang GP IEEE TI A model of stimulus induced epileptic spike-wave discharges SO 2013 IEEE SYMPOSIUM ON COMPUTATIONAL INTELLIGENCE, COGNITIVE ALGORITHMS, MIND, AND BRAIN (CCMB) LA English DT Proceedings Paper CT IEEE Symposium on Computational Intelligence, Cognitive Algorithms, Mind, and Brain (CCMB) CY APR 16-19, 2013 CL Singapore, SINGAPORE SP IEEE, IEEE Computat Intelligence Soc DE Epilepsy; EEG; Mathematical modelling; Spatiotemporal patterns; Spike-wave ID ABSENCE SEIZURES; NETWORK MECHANISMS; DYNAMICAL DISEASES; BRAIN SYSTEMS; WAG/RIJ RATS; FOCUS; SYNCHRONIZATION; CONNECTIVITY; COMPLEXES; FIELDS AB Recent clinical and experimental evidence suggests that the spike-wave discharges (SWD) of absence seizures result from local activity within a hyperexcitable cortical region with rapid generalization through thalamocortical networks. The cortical focus is said to react more strongly to stimulation than other areas. We seek to develop a model which is in agreement with these recent experimental findings and suggest a possible explanation. In this study we extend an existing neural field model of thalamocortical interaction to account for multiple cortical regions which are connected according connectivity inferred from a clinically diagnosed epileptic patient. We stimulate at different model electrodes and investigate the resulting seizure duration. We observe that stimulation of only a small subset (11%) of model electrodes can lead to the rapid generalisation of SWD via both corticocortical and thalamocortical pathways. We find that the resulting model dynamics (seizure duration) varies significantly dependent upon the nodes stimulated and the amplitude of the stimulus. Our model indicates that heterogeneities in corticocortical connectivity could serve as a possible reason for the cortical focus and provides a platform for in silico hypothesis generation in complement to in vivo hypothesis validation. C1 [Taylor, Peter N.; Dauwels, Justin] Nanyang Technol Univ, Sch Elect & Elect Engn, Singapore 639798, Singapore. [Wang, Yujiang] Univ Manchester, Manchester Interdisciplinary Bioctr, Manchester M1 7DN, Lancs, England. [Baier, Gerold] Heidelberg Univ, Ctr Organismal Stud, Modelling Biol Proc, D-69115 Heidelberg, Germany. [Cash, Sydney S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cash, Sydney S.] Harvard Med Sch, Cambridge, MA USA. [Slotine, Jean-Jacques] MIT, Dept Mech Engn, Dept Brain & Cognitive Sci, Cambridge, MA USA. RP Taylor, PN (reprint author), Nanyang Technol Univ, Sch Elect & Elect Engn, Singapore 639798, Singapore. EM ptaylor@ntu.edu.sg OI Taylor, Peter/0000-0003-2144-9838 NR 36 TC 7 Z9 7 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4673-5871-2 PY 2013 BP 53 EP 59 PG 7 WC Computer Science, Artificial Intelligence; Mathematical & Computational Biology SC Computer Science; Mathematical & Computational Biology GA BA4AH UT WOS:000335266900009 ER PT J AU Li, JZ Lo, J Dugast, AS Benedict, K Ribaudo, HJ Cesa, K Heisey, A Kuritzkes, DR Alter, G Landay, A Grinspoon, S Pereyra, F AF Li, J. Z. Lo, J. Dugast, A. S. Benedict, K. Ribaudo, H. J. Cesa, K. Heisey, A. Kuritzkes, D. R. Alter, G. Landay, A. Grinspoon, S. Pereyra, F. TI Relationship and clinical significance of soluble markers of inflammation and low-level viraemia in HIV-1 elite controllers SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT International Workshop on HIV and Hepatitis Virus Drug Resistance and Curative Strategies CY JUN 04-08, 2013 CL Toronto, CANADA C1 [Li, J. Z.; Heisey, A.; Kuritzkes, D. R.; Pereyra, F.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Cambridge, MA 02138 USA. [Lo, J.; Grinspoon, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dugast, A. S.; Cesa, K.; Alter, G.; Pereyra, F.] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. [Benedict, K.] MIT, Cambridge, MA 02139 USA. [Ribaudo, H. J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Landay, A.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. RI Dugast, AnneSophie/L-9541-2015 NR 0 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 2013 VL 18 SU 1 BP A28 EP A28 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA AG2ES UT WOS:000335229500024 ER PT B AU Alexander, S Hoppin, AG Baur, LA AF Alexander, Shirley Hoppin, Alison G. Baur, Louise A. BA Steinbeck, K Kohn, M BF Steinbeck, K Kohn, M TI Key Issues in Adolescent Obesity SO CLINICAL HANDBOOK IN ADOLESCENT MEDICINE: A GUIDE FOR HEALTH PROFESSIONALS WHO WORK WITH ADOLESCENTS AND YOUNG ADULTS LA English DT Article; Book Chapter ID CHILDREN C1 [Alexander, Shirley] Sydney Childrens Hosp Network Westmead, Sydney, NSW, Australia. [Hoppin, Alison G.] Massachusetts Gen Hosp Weight Ctr, Pediat Programs, Boston, MA USA. [Hoppin, Alison G.] Harvard Univ, Sch Med, Boston, MA USA. [Baur, Louise A.] Univ Sydney, Discipline Paediat & Child Hlth, Sydney Med Sch, Sydney, NSW 2006, Australia. [Baur, Louise A.] Univ Sydney, Sydney Sch Publ Hlth, Sydney, NSW 2006, Australia. [Baur, Louise A.] Sydney Childrens Hosp Network Westmead, Sydney, NSW, Australia. RP Alexander, S (reprint author), Sydney Childrens Hosp Network Westmead, Sydney, NSW, Australia. NR 11 TC 0 Z9 0 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 978-981-4374-04-0; 978-981-4374-03-3 PY 2013 BP 279 EP 294 D2 10.1142/8294 PG 16 WC Primary Health Care; Medicine, General & Internal; Pediatrics SC General & Internal Medicine; Pediatrics GA BA1DV UT WOS:000332410800024 ER PT S AU Kelly, SK Shire, DB Chen, JH Gingerich, MD Cogan, SF Drohan, WA Ellersick, W Krishnan, A Behan, S Wyatt, JL Rizzo, JF AF Kelly, Shawn K. Shire, Douglas B. Chen, Jinghua Gingerich, Marcus D. Cogan, Stuart F. Drohan, William A. Ellersick, William Krishnan, Ashwati Behan, Sonny Wyatt, John L. Rizzo, Joseph F., III GP IEEE TI DEVELOPMENTS ON THE BOSTON 256-CHANNEL RETINAL IMPLANT SO ELECTRONIC PROCEEDINGS OF THE 2013 IEEE INTERNATIONAL CONFERENCE ON MULTIMEDIA AND EXPO WORKSHOPS (ICMEW) SE IEEE International Conference on Multimedia and Expo Workshops LA English DT Proceedings Paper CT IEEE International Conference on Multimedia and Expo Workshops (ICMEW) CY JUL 15-19, 2013 CL San Jose, CA SP IEEE DE Biomedical engineering; biomedical electrodes; integrated circuit design; retinal prosthesis ID STIMULATION; PROSTHESIS AB A hermetic neurostimulator is being developed to restore functional sight to the blind. The latest developments are presented on the Boston 256-channel retinal prosthesis. The device includes a hermetic package made of titanium and alumina, containing an integrated circuit chip with 256 independently addressable current drivers. The prosthesis attaches to the outside scleral wall of the eye and electrically drives a microfabricated thin-film polyimide array of sputtered iridium oxide electrodes. This array is implanted in the subretinal space via a flap in the sclera. The implanted device receives power and stimulation data wirelessly via inductively coupled coils. A circuit to prevent residual electrode voltage and improve safety is being designed for incorporation into future devices. The components of our prosthesis have been tested, and we plan to implant the 256-channel device in animals this year. C1 [Kelly, Shawn K.; Shire, Douglas B.] Dept Vet Affairs, Pittsburgh, PA 15213 USA. [Kelly, Shawn K.; Krishnan, Ashwati] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. [Shire, Douglas B.; Gingerich, Marcus D.] Cornell Univ, Ithaca, NY 14853 USA. [Chen, Jinghua; Rizzo, Joseph F., III] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Cogan, Stuart F.] EIC Labs, Norwood, MA 02062 USA. [Drohan, William A.; Wyatt, John L.] MIT, Cambridge, MA 02139 USA. [Ellersick, William] Analog Circuit Works, Sudbury, MA 01776 USA. [Behan, Sonny] Sonny Behan Consulting, Atlanta, GA 30302 USA. RP Kelly, SK (reprint author), Dept Vet Affairs, Pittsburgh, PA 15213 USA. EM skkelly@cmu.edu FU Department of Veterans Affairs; NIH [EY016674-01]; Department of Defense; NSF's; Cornell Nanoscale Science and Technology Facility FX Funding provided by the Department of Veterans Affairs, NIH EY016674-01, Department of Defense, and NSFs support of the Cornell Nanoscale Science and Technology Facility. MOSIS provided in-kind foundry services. NR 20 TC 0 Z9 0 U1 0 U2 3 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2330-7927 J9 IEEE INT CONF MULTI PY 2013 PG 6 WC Computer Science, Hardware & Architecture; Computer Science, Information Systems; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BA4AC UT WOS:000335245800230 ER PT J AU Boutrus, RR Raad, RFA Kuter, I Ancukiewicz, M Roberts, L Solomon, N Ngo, T Borick, H Ryan, P Moy, B Gadd, M Chien, J Younger, J Smith, B Taghian, AG Harris, L AF Boutrus, Rimoun R. Raad, Rita F. Abi Kuter, Irene Ancukiewicz, Marek Roberts, Lisa Solomon, Natalie Ngo, Taylor Borick, Heather Ryan, Paula Moy, Beverly Gadd, Michele Chien, Jo Younger, Jerry Smith, Barbara Taghian, Alphonse G. Harris, Lyndsay TI Circulating tumor cells as predictors of response and failure in breast cancer patients treated with preoperative chemotherapy SO INTERNATIONAL JOURNAL OF BIOLOGICAL MARKERS LA English DT Article DE Breast cancer; Circulating tumor cells; Preoperative chemotherapy; Reverse transcription polymerase chain reaction ID RNA-POSITIVE CELLS; PERIPHERAL-BLOOD; NEOADJUVANT CHEMOTHERAPY; EPITHELIAL-CELLS; BONE-MARROW; RT-PCR; DISEASE; MRI; MAMMOGRAPHY; SURVIVAL AB Aim: To explore the significance of circulating tumor cells (CTCs) detection in the course of preoperative chemotherapy (PC) and their effect on the outcomes. Methods: Fifty-five patients with stage II/III invasive breast cancer were enrolled into a preoperative clinical trial. Patients were given PC with sequential single-agent doxorubicin and paclitaxel vs paclitaxel followed by doxorubicin. Blood samples (8 mL) were collected from patients before PC, after each phase, and at 6 months intervals during follow-up. Peripheral blood mononuclear cells were isolated and enriched for epithelial cells. Quantitative RT-PCR was used to determine the presence of cytokeratin 19 (CK19) mRNA. Samples were considered positive when the PCR curve crossed the standard threshold curve. Results: After the first phase of chemotherapy, there was a 59% overall reduction in the median tumor volume. The percentage of volume reduction did not differ between patients who presented with detectable CTCs at baseline and those who did not (p=0.89). After the second phase of chemotherapy, there was a further decrease in the median tumor volume to 93% from baseline. There was no correlation between the lack of response and the presence of CTCs either after the first (p=0.36) or second (p=0.5391) phases of PC. The presence of CTCs was a predictor of local or distant relapse (p=0.0411). The detection of CTCs did not affect overall survival (p=0.2569). Conclusion: CTCs can be used as predictors of relapse after definitive treatment of locally advanced breast cancer; however, CTCs detection in peripheral blood during the course of PC does not implicate a particular pattern of response to treatment. C1 [Boutrus, Rimoun R.; Raad, Rita F. Abi; Ancukiewicz, Marek; Taghian, Alphonse G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Kuter, Irene; Ryan, Paula; Moy, Beverly; Younger, Jerry] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Hematol Oncol Unit, Boston, MA USA. [Roberts, Lisa; Solomon, Natalie] Abbott Mol Inc, Des Plaines, IL USA. [Gadd, Michele; Smith, Barbara] Harvard Univ, Sch Med, Dept Surg, Div Surg Oncol,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ngo, Taylor; Borick, Heather] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol Adult Oncol, Boston, MA 02115 USA. [Chien, Jo] Univ Calif San Francisco, Dept Med, Div Hematol Oncol, San Francisco, CA USA. [Harris, Lyndsay] Yale Univ, Sch Med, Yale Canc Ctr, Breast Canc Program,Sect Med Oncol, New Haven, CT USA. RP Taghian, AG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St Cox Bldg 302, Boston, MA 02114 USA. EM ataghian@partners.org FU Avon-NCI Progress for Patients Award on the Dana-Farber/Harvard Cancer Center SPORE in Breast Cancer [CA089393] FX This study was supported in part by an Avon-NCI Progress for Patients Award on the Dana-Farber/Harvard Cancer Center SPORE in Breast Cancer CA089393. The study was approved by the institutional review board of the Massachusetts General Hospital and the Dana-Farber Cancer Institute. NR 32 TC 3 Z9 3 U1 0 U2 5 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 0393-6155 EI 1724-6008 J9 INT J BIOL MARKER JI Int. J. Biol. Markers PD JAN-MAR PY 2013 VL 28 IS 1 BP 17 EP 23 DI 10.5301/JBM.2012.9580 PG 7 WC Biotechnology & Applied Microbiology; Oncology SC Biotechnology & Applied Microbiology; Oncology GA AG1LF UT WOS:000335176000003 PM 23015398 ER PT J AU Oh, JE Cho, YW Scarcelli, G Kim, YH AF Oh, Joo-Eon Cho, Young-Wook Scarcelli, Giuliano Kim, Yoon-Ho GP IEEE TI Sub-Rayleigh Imaging with Incoherent Light SO 2013 CONFERENCE ON LASERS AND ELECTRO-OPTICS PACIFIC RIM (CLEO-PR) LA English DT Proceedings Paper CT 10th Conference on Lasers and Electro-Optics Pacific Rim (CLEO-PR) CY JUN 30-JUL 04, 2013 CL Kyoto, JAPAN SP IEICE Commun Soc, IEICE Elect Soc, Japan Soc Appl Phys, IEEE Photon Soc, Opt Soc, Opt Soc Korea, Korean Phys Soc, Agilent Technologies Japan Ltd, Hamamatsu Photon K K, Tektronix Japan, Thorlabs Japan Inc AB We demonstrate sub-Rayleigh limit imaging of an object via speckle illumination. Imaging beyond the conventional Rayleigh limit is achieved by illuminating the object with pseudothermal light that exhibits a random speckle pattern. An object image is reconstructed from the second-order correlation measurement and the resolution of the image, which exceeds the Rayleigh limit, is shown to be related to the size of the speckle pattern that is tied to the lateral coherence length of the pseudothermal light. C1 [Oh, Joo-Eon; Cho, Young-Wook; Kim, Yoon-Ho] Pohang Univ Sci & Technol POSTECH, Dept Phys, Pohang 790784, South Korea. [Scarcelli, Giuliano] Massachusetts Gen Hosp, Havard Med Sch, Wellman Ctr Photonmed, Boston, MA 02114 USA. RP Oh, JE (reprint author), Pohang Univ Sci & Technol POSTECH, Dept Phys, Pohang 790784, South Korea. FU National Research Foundation of Korea [2011-0021452, 2012-002588]; National Junior Research Fellowship [2011-0010895]; Harvard Clinical and Translational Science Center [UL1 RR 025758]; American Society for Laser Medicine and Surgery FX This work was supported in part by the National Research Foundation of Korea (2011-0021452 and 2012-002588). Y.-W.C. acknowledges support from the National Junior Research Fellowship (2011-0010895). G.S. acknowledges support from the Harvard Clinical and Translational Science Center (NIH \#UL1 RR 025758) and the American Society for Laser Medicine and Surgery. NR 6 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4673-6476-8 PY 2013 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BA3FB UT WOS:000334176100697 ER PT J AU Zhai, X Li, S Wang, S Wang, H Rong, P AF Zhai, X. Li, S. Wang, S. Wang, H. Rong, P. GP MEDIMOND TI Auricular Concha Electroacupuncture Improves Pain Behavior in Zucker Diabetic Fatty Rats SO 4TH INTERNATIONAL CONGRESS ON NEUROPATHIC PAIN LA English DT Proceedings Paper CT 4th International Congress on Neuropathic Pain CY MAY 23-26, 2013 CL Toronto, CANADA ID LONG-TERM; NEUROPATHY AB Painful neuropathy is a frequent comorbidity in diabetes. Zucker diabetic fatty (ZDF) rats develop type 2 diabetes spontaneously and show neuropathic pain by age of 13wk. Auricular Concha Electroacupuncture (ACEA) has been widely used and proven an effective therapy. In this study we show that ACEA effectively attenuated diabetic neuropathic pain in ZDF rats as detected by decreased thermal hyperalgesia and mechanical allodynia in hindpaw. This ameliorated pain behavior is related to an elevated serotonin (5-HT) plasma concentration, and an upregulated expression 5-HT1A receptor in hypothalamus. We conclude that ACEA relieve diabetic neuropathic pain through increasing plasma 5-HT concentration and upregulating expression of central 5-HT1A receptor. C1 [Zhai, X.; Li, S.; Wang, H.; Rong, P.] China Acad Chinese Med Sci, Inst Acupuncture & Moxibust, Beijing, Peoples R China. [Wang, S.] Xinxiang Med Univ, Xinxiang, Peoples R China. [Wang, S.] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02115 USA. RP Rong, P (reprint author), China Acad Chinese Med Sci, Inst Acupuncture & Moxibust, Beijing, Peoples R China. EM shuxingw@partners.org; rongpj@hotmail.com FU National Basic Research Program of China [2012CB518503]; National Natural Science Foundation of China [81271243]; National Science and Technology Ministry [2012BAF14B10] FX This work was supported by National Basic Research Program of China (973 Program)-2012CB518503; National Natural Science Foundation of China-81271243; and Project Supported National Science and Technology Ministry-2012BAF14B10. NR 8 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-688-3 PY 2013 BP 59 EP 63 PG 5 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA BA3VB UT WOS:000334913700014 ER PT J AU Kang, JX AF Kang, Jing X. TI Frontiers of Nutritional Intervention SO JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS LA English DT Editorial Material ID INFLAMMATION; MICROBIOTA; DISEASES; HEALTH C1 [Kang, Jing X.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, Lab Lipid Med & Technol, 149,13th St,Room 4001, Charlestown, MA 02129 USA. EM kang.jing@mgh.harvard.edu NR 7 TC 0 Z9 0 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-6499 EI 1661-6758 J9 J NUTRIGENET NUTRIGE JI J. Nutrigenet. Nutrigenomics PY 2013 VL 6 IS 6 BP I EP II DI 10.1159/000362481 PG 2 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA AF8XJ UT WOS:000334998600001 ER PT J AU Elze, T Benner, P Pasquale, L Shen, L Bex, P AF Elze, T. Benner, P. Pasquale, L. Shen, L. Bex, P. TI A Spatial Model of Visual Fields with Applications to Adaptive Sampling SO PERCEPTION LA English DT Meeting Abstract C1 [Elze, T.] Harvard Univ, Sch Med, Schepens Eye Res Inst, Cambridge, MA 02138 USA. [Benner, P.] Max Planck Inst Math Sci, Leipzig, Germany. [Pasquale, L.; Shen, L.] Massachusetts Eye & Ear Infirm, Boston, MA USA. [Bex, P.] Harvard Univ, Sch Med, Dept Ophthalmol, Cambridge, MA 02138 USA. EM tobias.elze@schepens.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU PION LTD PI LONDON PA 207 BRONDESBURY PARK, LONDON NW2 5JN, ENGLAND SN 0301-0066 EI 1468-4233 J9 PERCEPTION JI Perception PY 2013 VL 42 SU S BP 71 EP 71 PG 1 WC Ophthalmology; Psychology; Psychology, Experimental SC Ophthalmology; Psychology GA AF7NE UT WOS:000334901000221 ER PT S AU Wang, Y Li, DD Jiang, YY Mylonakis, E AF Wang, Yan Li, De-Dong Jiang, Yuan-Ying Mylonakis, Eleftherios BE Vilcinskas, A TI Utility of Insects for Studying Human Pathogens and Evaluating New Antimicrobial Agents SO YELLOW BIOTECHNOLOGY I: INSECT BIOTECHNOLOGIE IN DRUG DISCOVERY AND PRECLINICAL RESEARCH SE Advances in Biochemical Engineering-Biotechnology LA English DT Article; Book Chapter DE Antimicrobial efficacy; Drosophila; Galleria; Infection; Insect; Pathogen; Pathogenesis ID GALLERIA-MELLONELLA LARVAE; BURKHOLDERIA-CEPACIA COMPLEX; TOLL-DEFICIENT DROSOPHILA; STAPHYLOCOCCUS-AUREUS INFECTION; CANDIDA-ALBICANS INFECTION; BEETLE TRIBOLIUM-CASTANEUM; ANTIFUNGAL DRUG EFFICACY; INNATE IMMUNE-RESPONSE; GROUP-A STREPTOCOCCUS; BOMBYX-MORI L AB Insect models, such as Galleria mellonella and Drosophila melanogaster have significant ethical, logistical, and economic advantages over mammalian models for the studies of infectious diseases. Using these models, various pathogenic microbes have been studied and many novel virulence genes have been identified. Notably, because insects are susceptible to a wide variety of human pathogens and have immune responses similar to those of mammals, they offer the opportunity to understand innate immune responses against human pathogens better. It is important to note that insect pathosystems have also offered a simple strategy to evaluate the efficacy and toxicity of many antimicrobial agents. Overall, insect models provide a rapid, inexpensive, and reliable way as complementary hosts to conventional vertebrate animal models to study pathogenesis and antimicrobial agents. C1 [Wang, Yan; Li, De-Dong; Jiang, Yuan-Ying] Second Mil Med Univ, New Drug Res & Dev Ctr, Sch Pharm, Shanghai 200433, Peoples R China. [Wang, Yan; Mylonakis, Eleftherios] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02138 USA. [Mylonakis, Eleftherios] Brown Univ, Rhode Isl Hosp, Div Infect Dis, Warren Alpert Med Sch, Providence, RI 02903 USA. RP Wang, Y (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02138 USA. EM wangyansmmu@126.com; emylonakis@lifespan.org NR 224 TC 4 Z9 5 U1 2 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0724-6145 BN 978-3-642-39863-6; 978-3-642-39862-9 J9 ADV BIOCHEM ENG BIOT JI Adv. Biochem. Eng. Biotechnol. PY 2013 VL 135 BP 1 EP 25 DI 10.1007/10_2013_194 D2 10.1007/978-3-642-39863-6 PG 25 WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Engineering, Chemical SC Biotechnology & Applied Microbiology; Engineering GA BA1KR UT WOS:000332674000002 PM 23604210 ER PT S AU Yang, X Pu, Y Psaltis, D Stankovic, KM AF Yang, Xin Pu, Ye Psaltis, Demetri Stankovic, Konstantina M. BE Ferraro, P RitschMarte, M Grilli, S Stifter, D TI In situ imaging of the mouse cochlea using two-photon microscopy SO OPTICAL METHODS FOR INSPECTION, CHARACTERIZATION, AND IMAGING OF BIOMATERIALS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Optical Methods for Inspection, Characterization, and Imaging of Biomaterials CY MAY 15-16, 2013 CL Munich, GERMANY SP SPIE DE two photon microscopy; cochlea; diagnosis; noise trauma ID FLUORESCENCE MICROSCOPY; ROUND WINDOW AB Intracochlear imaging is of great interest clinically because cochlea is the central organ of hearing. However, intracochlear imaging is technologically challenging due to the cochlea's small size and encasement in bone. The state-of- the-art imaging techniques are not adequate for high resolution cellular imaging to establish diagnosis without destroying the cochlea. We report in situ imaging of intact mouse cochlea using endogenous two-photon excitation fluorescence (TPEF) as the contrast mechanism. TPEF eliminates the need for exogenous labeling and eradicating the staining-induced artifacts. We used a natural, membranous opening into the cochlea, the round window, as the optical access to reach the organ of Corti, requiring no additional slicing or opening. Our approach provides the maximum non-invasiveness in the imaging process. TPEF exhibits strong contrast allowing deep imaging of mouse cochlea with cellular and even subcellular resolution. Inner hair cell, outer hair cell and supporting cell are clearly identifiable in TPEF images. Distinct morphological differences are observed between healthy and noise-exposed cochleae, allowing detection of specific, noise-induced pathologic changes. The TPEF images taken through the round window are correlated with the whole mount sections, verifying their reliability. Compared with one-photon excitation fluorescence (OPEF) confocal microscope and wide-field transmission microscope images taken under the same magnification and resolution, TPEF images demonstrate clear advantages in terms of sharpness, signal to noise ratio and contrast. These capabilities provide a working foundation for microendoscopy-based clinical diagnostics of sensorineural hearing loss. C1 [Yang, Xin; Pu, Ye; Psaltis, Demetri] Ecole Polytech Fed Lausanne, Lausanne, Switzerland. [Stankovic, Konstantina M.] Harvard Med Sch, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02115 USA. RP Yang, X (reprint author), Ecole Polytech Fed Lausanne, Lausanne, Switzerland. FU Bertarelli Foundation FX We are grateful for the support of the Bertarelli Foundation. NR 14 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9608-9 J9 PROC SPIE PY 2013 VL 8792 AR UNSP 87920T DI 10.1117/12.2022523 PG 7 WC Biophysics; Materials Science, Characterization & Testing; Optics; Physics, Applied SC Biophysics; Materials Science; Optics; Physics GA BA2ZU UT WOS:000334027300016 ER PT S AU Nappi, JJ Do, S Yoshida, H AF Naeppi, Janne J. Synho Do Yoshida, Hiroyuki BE Yoshida, H Warfield, S Vannier, MW TI Computer-Aided Detection of Colorectal Lesions with Super-Resolution CT Colonography: Pilot Evaluation SO ABDOMINAL IMAGING: COMPUTATION AND CLINICAL APPLICATIONS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 5th International Workshop on Abdominal Imaging - Computational and Clinical Applications CY SEP 22, 2013 CL Nagoya, JAPAN DE Iterative reconstruction; super-resolution; domain decomposition; computer-aided detection; virtual colonoscopy ID POLYPS AB Reliable computer-aided detection (CADe) of small polyps and flat lesions is limited by the relatively low image resolution of computed tomographic colonography (CTC). We developed a sinogram-based super-resolution (SR) method to enhance the images of lesion candidates detected by CADe. First, CADe is used to detect lesion candidates at high sensitivity from conventional CTC images. Next, the signal patterns of the lesion candidates are enhanced in sinogram domain by use of non-uniform compressive sampling and iterative reconstruction to produce SR images of the lesion candidates. For pilot evaluation, an anthropomorphic phantom including simulated lesions was filled partially with fecal tagging and scanned by use of a CT scanner. A fully automated CADe scheme was used to detect lesion candidates in the images reconstructed at conventional 0.61-mm and at 0.10-mm SR image resolution. The proof-of-concept results indicate that the SR method has potential to reduce the number of FP CADe detections below that obtainable with the conventional CTC imaging technology. C1 [Naeppi, Janne J.; Synho Do; Yoshida, Hiroyuki] Massachusetts Gen Hosp Imaging, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. RP Nappi, JJ (reprint author), Massachusetts Gen Hosp Imaging, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. EM jnappi@partners.org; sdo@nmr.mgh.harvard.edu; yoshida.hiro@mgh.harvard.edu FU [CA095279]; [CA166816]; [CA131718] FX This work was supported in part by grants of CA095279, CA166816, and CA131718. NR 15 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0302-9743 BN 978-3-642-41082-6; 978-3-642-41083-3 J9 LECT NOTES COMPUT SC PY 2013 VL 8198 BP 73 EP 80 PG 8 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods; Imaging Science & Photographic Technology SC Computer Science; Imaging Science & Photographic Technology GA BA2LK UT WOS:000333644000009 ER PT S AU Ryu, Y Nappi, JJ Phan, M Yoshida, H AF Ryu, Yasuji Naeppi, Janne J. Minh Phan Yoshida, Hiroyuki BE Yoshida, H Warfield, S Vannier, MW TI Computer-Aided Detection of Non-polypoid Flat Lesions in CT Colonography: Observer Performance Study SO ABDOMINAL IMAGING: COMPUTATION AND CLINICAL APPLICATIONS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 5th International Workshop on Abdominal Imaging - Computational and Clinical Applications CY SEP 22, 2013 CL Nagoya, JAPAN DE CT colonography; flat lesions; non-polypoid lesions; computer-assisted detection; observer study ID COLORECTAL-CANCER; TOMOGRAPHIC COLONOGRAPHY; CHALLENGES; ACCURACY; TRIAL; CAD AB To evaluate the effect of computer-aided detection (CADe) on the performance of human readers in the detection of non-polypoid flat lesions from a large computed tomography (CT) colonography population. A total of 153 cathartic CT colonography cases, including 45 colonoscopy-confirmed, morphologically flat lesions, were sampled from a European multi-center CT colonography trial for asymptomatic patients at increased risk of colorectal cancer. Two readers (expert and non-expert) reviewed the 153 CT colonography cases and recorded all detected lesions using primary 3D interpretation and a CADe second-read paradigm. There were 17 patients with 18 flat lesions >= 10 mm in size and 17 patients with 27 flat lesions 6 - 9 mm in size. For the flat lesions >= 10 mm, per-patient sensitivities of the expert reader for unassisted and CADe-assisted readings were 59% [95% CI: 36-78%] and 71% [47-87%], respectively, whereas those of the non-expert reader were 41% [21-65%] and 47% [37-59%], respectively. For 6-9 mm flat lesions, the corresponding per-patient sensitivities of the expert reader were 59% [36-78%] and 76% [53-89%], respectively, whereas those of the non-expert were 47% [37-59%] and 82% [59-93%]. The results indicate that the use of CADe can increase the sensitivity of human readers in the detection of flat lesions in a screening setting. C1 [Ryu, Yasuji; Naeppi, Janne J.; Minh Phan; Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. RP Ryu, Y (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. EM yryu@partners.org; jnappi@partners.org; mphan4@partners.org; yoshida.hiro@mgh.harvard.edu FU NCI at the NIH [CA131718]; [CA095279] FX This work was supported in part by grants of CA095279 and CA131718 from the NCI at the NIH. NR 18 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0302-9743 BN 978-3-642-41082-6; 978-3-642-41083-3 J9 LECT NOTES COMPUT SC PY 2013 VL 8198 BP 81 EP 88 PG 8 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods; Imaging Science & Photographic Technology SC Computer Science; Imaging Science & Photographic Technology GA BA2LK UT WOS:000333644000010 ER PT S AU Do, S Nappi, JJ Yoshida, H AF Synho Do Naeppi, Janne J. Yoshida, Hiroyuki BE Yoshida, H Warfield, S Vannier, MW TI Iterative Reconstruction for Ultra-Low-Dose Laxative-Free CT Colonography SO ABDOMINAL IMAGING: COMPUTATION AND CLINICAL APPLICATIONS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 5th International Workshop on Abdominal Imaging - Computational and Clinical Applications CY SEP 22, 2013 CL Nagoya, JAPAN DE Iterative reconstruction; non-cathartic; dose; radiation; virtual colonoscopy ID POLYPS AB Iterative reconstruction (IRT) makes it possible to acquire computed tomographic colonography (CTC) images at <50% of the radiation dose of conventional standard-dose filtered back-projection (FBP) without impairing image quality. It has also other significant advantages over FBP, including better noise suppression, reduction of image artifacts, and flexible mathematical formulation. In this pilot study, we explored the potential application of IRT in the implementation of an ultra-low-dose (ULD) laxative-free CTC examination. First, CTC images are reconstructed approximately with FBP to detect regions of fecal tagging and other high-density objects that can generate image artifacts. Next, the detected regions are projected to sinogram domain to guide the IRT process for the minimization of image noise, correction of beam-hardening artifacts, and virtual cleansing of fecal-tagged regions. For pilot evaluation, five patients were prepared for an ULD dual-energy CTC examination by use of non-cathartic dietary fecal tagging with iodine. For one patient, the CTC images were reconstructed by use of both the FBP and IRT methods. Preliminary results showed that the IRT-reconstructed images demonstrated superior image quality over the FBP-reconstructed images. C1 [Synho Do] Massachusetts Gen Hosp Imaging, Boston, MA 02114 USA. RP Do, S (reprint author), Massachusetts Gen Hosp Imaging, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. EM sdo@nmr.mgh.harvard.edu; jnappi@partners.org; yoshida.hiro@mgh.harvard.edu NR 15 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0302-9743 BN 978-3-642-41082-6; 978-3-642-41083-3 J9 LECT NOTES COMPUT SC PY 2013 VL 8198 BP 99 EP 106 PG 8 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods; Imaging Science & Photographic Technology SC Computer Science; Imaging Science & Photographic Technology GA BA2LK UT WOS:000333644000012 ER PT S AU Lee, SH Ryu, Y Hayano, K Yoshida, H AF Lee, Sang Ho Ryu, Yasuji Hayano, Koichi Yoshida, Hiroyuki BE Yoshida, H Warfield, S Vannier, MW TI Continuous-Time Flow-Limited Modeling by Convolution Area Property and Differentiation Product Rule in 4-Phase Liver Dynamic Contrast-Enhanced CT SO ABDOMINAL IMAGING: COMPUTATION AND CLINICAL APPLICATIONS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 5th International Workshop on Abdominal Imaging - Computational and Clinical Applications CY SEP 22, 2013 CL Nagoya, JAPAN DE Continuous-time tracer kinetic modeling; convolution area property; differentiation product rule; four-phase dynamic contrast-enhanced CT ID COMPUTED-TOMOGRAPHY; PERFUSION; MRI; IMAGES AB Parametric-fitting approaches for tracer kinetic modeling depend on the capability of a computational method to describe underlying physiologic processes that cause temporal intensity changes in dynamic contrast-enhanced (DCE) images. Rapid scan techniques allow perfusion CT imaging with high temporal resolution. In clinical practice, however, the perfusion CT protocol is especially a trade-off between the number of data points and the total radiation dose. Considering availability and radiation exposure, use of DCE-CT imaging derived from 4 temporal phases, which include precontrast, arterial, portal, and delayed phases, is highly desirable for the liver. However, low-temporal-resolution images like 4-phase liver DCE-CT present several barriers to modeling of tracer kinetics because of the lack of temporal enhancement data, which limits obtaining reliable physiologic information. The major reason for the limited application of a tracer kinetic model in temporally sparse dynamic data is that general computational algorithms such as deconvolution techniques require discretizing of arterial (or portal-vein) and tissue curves for estimation of kinetic parameters, leading to an unstable computational solution. The numerical instability due to the discretization of the enhancement curves can be more pronounced in the low-temporal-resolution data like those gleaned from 4-phase DCE-CT. For this reason, we propose a novel dual-input continuous-time tracer kinetic modeling method based on a new mathematical approach that uses the convolution area property and the differentiation product rule, without any discretization of the enhancement curves. This model was applied to case studies of hepatocellular carcinoma in 4-phase DCE-CT to illustrate the potential effectiveness of continuous-time tracer kinetic modeling. The proposed analytic scheme was shown to be feasible for estimation of kinetic parameters even in 4-phase liver DCE-CT, potentially being a practical guide for tracer kinetic model-based curve-fitting in temporally sparse data. C1 [Lee, Sang Ho; Ryu, Yasuji; Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. [Hayano, Koichi] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Lee, SH (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. EM lee.sangho@mgh.harvard.edu; yoshida.hiro@mgh.harvard.edu; khayano@partners.org; yryu@partners.org NR 21 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0302-9743 BN 978-3-642-41082-6; 978-3-642-41083-3 J9 LECT NOTES COMPUT SC PY 2013 VL 8198 BP 259 EP 269 PG 11 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods; Imaging Science & Photographic Technology SC Computer Science; Imaging Science & Photographic Technology GA BA2LK UT WOS:000333644000029 ER PT S AU Lee, SH Hayano, K Sahani, D Yoshida, H AF Lee, Sang Ho Hayano, Koichi Sahani, Dushyant Yoshida, Hiroyuki BE Yoshida, H Warfield, S Vannier, MW TI Use of Tracer Kinetic Model-Driven Biomarkers for Monitoring Antiangiogenic Therapy of Hepatocellular Carcinoma in First-Pass Perfusion CT SO ABDOMINAL IMAGING: COMPUTATION AND CLINICAL APPLICATIONS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 5th International Workshop on Abdominal Imaging - Computational and Clinical Applications CY SEP 22, 2013 CL Nagoya, JAPAN DE Hepatocellular carcinoma; antiangiogenic treatment; image biomarker; perfusion CT ID TUMOR PERFUSION; COMPUTED-TOMOGRAPHY; CANCER; DENSITY; RECIST; LIVER AB Development of vascularly targeted anti-cancer therapies has led to an interest in determining the in vivo effectiveness of anti-tumor agents in patients. As the antiangiogenic agents may have significant effects without causing tumor shrinkage, their microcirculatory characteristics have the potential to be response biomarkers. Perfusion CT (PCT) studies can quantify the microcirculatory status of liver tumors, and can be used for assessing the effectiveness of antiangiogenic therapy. Our purpose in this study was to compare five different tracer kinetic models for the analysis of first-pass hepatic PCT data, to investigate whether kinetic parameters differ in significance among different kinetic models, and to select the best single prognostic biomarker with respect to the prediction of 6-month progression-free survival (PFS) of patients with advanced hepatocellular carcinoma (HCC). The first-pass PCT was performed at baseline and on days 10 to 12 after initiation of antiangiogenic treatment. The PCT data were analyzed retrospectively by the Tofts-Kety (TK), extended TK (ETK), two-compartment exchange (2CX), adiabatic approximation to tissue homogeneity (AATH), and distributed parameter (DP) models. Kinetic parameters consisted of blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability-surface area product (PS), mean values of which within HCC were compared between baseline and post-treatment by the Wilcoxon signed-rank test. Baseline mean kinetic parameters within HCC and relative percent changes (%changes) in the mean and standard deviation (SD) from baseline to post-treatment were also compared in terms of PFS discrimination by use of Spearman correlation analysis. After treatment, the changes in the kinetic parameter values were significantly different among models. The results suggested that the %change of SD for BV is an effective prognosis biomarker, potentially reflecting that treatment-induced change of vascular heterogeneity plays a role in the assessment of the HCC response. Based on the predictive ranking of a single biomarker, the AATH model was the best predictor of 6-month PFS in the first-pass PCT analysis. C1 [Lee, Sang Ho; Yoshida, Hiroyuki] Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. [Hayano, Koichi; Sahani, Dushyant] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Lee, SH (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. EM lee.sangho@mgh.harvard.edu; khayano@partners.org; dsahani@partners.org; yoshida.hiro@mgh.harvard.edu NR 20 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0302-9743 BN 978-3-642-41082-6; 978-3-642-41083-3 J9 LECT NOTES COMPUT SC PY 2013 VL 8198 BP 270 EP 279 PG 10 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods; Imaging Science & Photographic Technology SC Computer Science; Imaging Science & Photographic Technology GA BA2LK UT WOS:000333644000030 ER PT S AU Day, ML Delgutte, B AF Day, Mitchell L. Delgutte, Bertrand BE Moore, BCJ Patterson, RD Winter, IM Carlyon, RP Gockel, HE TI Neural Correlates of the Perception of Sound Source Separation SO BASIC ASPECTS OF HEARING: PHYSIOLOGY AND PERCEPTION SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 16th International Symposium on Hearing (ISH) CY JUL 23-27, 2012 CL St Johns Coll, Cambridge, ENGLAND SP GNResound, MED EL, Eriksholm Res Ctr, Phonak, Starkey, Widex HO St Johns Coll ID INTERAURAL TIME; REVERBERATION; LOCALIZATION; SENSITIVITY; CONCURRENT AB As two sound sources become spatially separated in the horizontal plane, the binaural cues used for sound localization become distorted from their values for each sound in isolation. Because firing rates of most neurons in the inferior colliculus (IC) are sensitive to these binaural cues, we hypothesized that these neurons would be sensitive to source separation. We examined changes in the target azimuth tuning functions of IC neurons in unanesthetized rabbits caused by the concurrent presentation of an interferer at a fixed spatial location. Both target and interferer were broadband noise bursts, uncorrelated with each other. Signal detection analysis of firing rates of individual IC neurons shows that responses are correlated with psychophysical performance on segregation of spatially separated sources. The analysis also highlights the role of neural sensitivity to interaural time differences of cochlea-induced envelopes in performing this task. Psychophysical performance on source segregation was also compared to the performance of two contrasting maximum-likelihood classifiers operating on the firing rates of the population of IC neurons. The "population-pattern" classifier had access to the firing rates of every neuron in the population, while the "two-channel" classifier operated on the summed firing rates from each side of the brain. Unlike the two-channel classifier, the population-pattern classifier could segregate the sources accurately, suggesting that some of the information contained in the heterogeneity of azimuth tuning functions across IC neurons is used to segregate sources. C1 [Day, Mitchell L.; Delgutte, Bertrand] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Day, Mitchell L.; Delgutte, Bertrand] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Delgutte, Bertrand] MIT, Elect Res Lab, Cambridge, MA 02139 USA. RP Day, ML (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM day@meei.harvard.edu OI Day, Mitchell/0000-0002-2754-234X; , /0000-0003-1349-9608 FU NIDCD (US) [R01 DC002258, P30 DC005209] FX This work was supported by NIDCD (US) grants R01 DC002258 and P30 DC005209. NR 10 TC 0 Z9 0 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0065-2598 BN 978-1-4614-1590-9; 978-1-4614-1589-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2013 VL 787 BP 255 EP 262 DI 10.1007/978-1-4614-1590-9_29 PG 8 WC Medicine, Research & Experimental; Neurosciences; Otorhinolaryngology; Physiology SC Research & Experimental Medicine; Neurosciences & Neurology; Otorhinolaryngology; Physiology GA BA2DG UT WOS:000333329600030 PM 23716231 ER PT S AU Chung, Y Hancock, KE Nam, SI Delgutte, B AF Chung, Yoojin Hancock, Kenneth E. Nam, Sung-Il Delgutte, Bertrand BE Moore, BCJ Patterson, RD Winter, IM Carlyon, RP Gockel, HE TI Better Temporal Neural Coding with Cochlear Implants in Awake Animals SO BASIC ASPECTS OF HEARING: PHYSIOLOGY AND PERCEPTION SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 16th International Symposium on Hearing (ISH) CY JUL 23-27, 2012 CL St Johns Coll, Cambridge, ENGLAND SP GNResound, MED EL, Eriksholm Res Ctr, Phonak, Starkey, Widex HO St Johns Coll ID INTERAURAL TIME DIFFERENCES; INFERIOR COLLICULUS; ELECTRICAL-STIMULATION; NEURONS; SENSITIVITY; CORTEX AB Both the performance of cochlear implant (CI) listeners and the responses of auditory neurons show limits in temporal processing at high frequencies. However, the upper limit of temporal coding of pulse-train stimuli in the inferior colliculus (IC) of anesthetized animals appears to be lower than that observed in corresponding perceptual tasks. We hypothesize that the neural rate limits have been underestimated due to the effect of anesthesia. To test this hypothesis, we developed a chronic, awake rabbit preparation for recording responses of single IC neurons to CI stimulation without the confound of anesthesia and compared these data with earlier recordings from the IC of anesthetized cats. Stimuli were periodic trains of biphasic pulses with rates varying from 20 to 1,280 pulses per second (pps). We found that the maximum pulse rates that elicited sustained firing and phase-locked responses were 2-3 times higher in the IC of awake rabbits than in anesthetized cats. Moreover, about 25 % of IC neurons in awake rabbit showed sustained responses to periodic pulse trains at much higher pulse rates (>1,000 pps) than observed in anesthetized animals. Similar differences were observed in single units whose responses to pulse trains were monitored while the animal was given an injection of an ultrashort-acting anesthetic. In general, the physiological rate limits of IC neurons in awake rabbit are more consistent with the psychophysical limits in human CI subjects compared to the data from anesthetized animals. C1 [Chung, Yoojin; Hancock, Kenneth E.; Delgutte, Bertrand] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Chung, Yoojin; Hancock, Kenneth E.; Nam, Sung-Il; Delgutte, Bertrand] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Nam, Sung-Il] Keimyung Univ, Sch Med, Dept Otolaryngol, Taegu, South Korea. [Delgutte, Bertrand] MIT, Elect Res Lab, Cambridge, MA 02139 USA. RP Chung, Y (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. EM yoojin.chung@gmail.com OI Chung, Yoojin/0000-0002-8772-5308; , /0000-0003-1349-9608 FU NIH [R01DC005775, P30DC005209]; Massachusetts Eye and Ear and a Hearing Health Foundation grant FX Supported by NIH grants R01DC005775 and P30DC005209, Curing Kids Fund from Massachusetts Eye and Ear and a Hearing Health Foundation grant to Y. Chung. We thank Connie Miller, Melissa McKinnon, and Mike Kaplan for technical assistance. NR 17 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0065-2598 BN 978-1-4614-1590-9; 978-1-4614-1589-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2013 VL 787 BP 353 EP 361 DI 10.1007/978-1-4614-1590-9_39 PG 9 WC Medicine, Research & Experimental; Neurosciences; Otorhinolaryngology; Physiology SC Research & Experimental Medicine; Neurosciences & Neurology; Otorhinolaryngology; Physiology GA BA2DG UT WOS:000333329600040 PM 23716241 ER PT J AU He, YZ Yu, HQ Sun, S Wang, YF Liu, LM Chen, ZY Li, HW AF He, Yingzi Yu, Huiqian Sun, Shan Wang, Yunfeng Liu, Liman Chen, Zhengyi Li, Huawei TI Trans-2-phenylcyclopropylamine regulates zebrafish lateral line neuromast development mediated by depression of LSD1 activity SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE hair cell; LSD1; neuromast; trans-2-phenylcydopropylamine; zebrafish ID HISTONE LYSINE METHYLATION; HAIR CELL-DEVELOPMENT; DEMETHYLASE LSD1; DANIO-RERIO; PROLIFERATION; MORPHOGENESIS; REGENERATION; EXPRESSION; MIGRATION; SYSTEM AB The zebrafish mechanosensory lateral line (LL) is a model system for the study of hair cell development, survival and regeneration. Recently, histone modifications have attracted a considerable amount of interest because of their indispensable roles in various kinds of cellular processes including differentiation, proliferation, apoptosis and function. Lysine specific demethylase 1 (LSD1) is an important enzyme that regulates histone methylation. As a transcriptional regulator, this enzyme has broad functional activities and is involved in many biological processes. However, the effects of LSD1 on the early development of zebrafish sensory system have not been fully elucidated. Here, we have found that pharmacological inhibition of LSD1 with the monoamine oxidase (MAO) inhibitor trans-2-phenylcyclopropylamine (referred to as 2-PCPA) reduced the numbers of both sensory hair cells and supporting cells of neuromasts during zebrafish development. Our results showed that the treatment of zebrafish larvae with 2-PCPA caused accumulation of histone methylation and suppressed proliferation of neuromast cells. Finally, acridine orange staining assay demonstrated that 2-PCPA treatment at high concentrations induced an enhancement of cellular apoptosis within neuromasts. Taken together,these results indicate that LSD1 demethylase activity is required for neuromast development in zebrafish larvae. C1 [He, Yingzi; Wang, Yunfeng; Liu, Liman; Li, Huawei] Fudan Univ, Inst Biomed Sci, Shanghai 200031, Peoples R China. [He, Yingzi; Yu, Huiqian; Sun, Shan; Li, Huawei] Fudan Univ, Affiliated Eye & ENT Hosp, Dept Otolaryngol, Shanghai 200031, Peoples R China. [Chen, Zhengyi] Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02115 USA. [Chen, Zhengyi] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Chen, Zhengyi] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Li, HW (reprint author), Fudan Univ, EENT Hosp, Dept Otolaryngol, Shanghai 200031, Peoples R China. EM lihuawei09611@163.com FU Major State Basic Research Development Program of China (973 Program) [2011CB504506]; National Natural Science Foundation of China [81230019, 81070793, 30901668]; National Natural Science Foundation for Youth of China [81100721]; Shanghai Rising-Star Program [12QA1400500]; Program for Changjiang Scholars and Innovative Research Team in University [IRT1010]; Science and Technology Commission of Shanghai Municipality [09DJ1400602]; Program of Outstanding Shanghai Academic Leader [11XD1401300]; Program of Leading Medical Personnel in Shanghai; Innovation Programme of Major Basic Research Project FX The authors would like to thank Min Yu, Jingying Hu, and Shaoyang Sun for their expert fish care, and Yalin Huang for technical assistance. This work was supported by grants from the Major State Basic Research Development Program of China (973 Program) (2011CB504506), the National Natural Science Foundation of China (No. 81230019, 81070793, 30901668), the National Natural Science Foundation for Youth of China (No.81100721), and Sponsored by Shanghai Rising-Star Program (12QA1400500), the Program for Changjiang Scholars and Innovative Research Team in University(IRT1010), the Innovation Programme of Major Basic Research Project, the Science and Technology Commission of Shanghai Municipality (09DJ1400602), the Program of Outstanding Shanghai Academic Leader (11XD1401300) and the Program of Leading Medical Personnel in Shanghai. NR 58 TC 11 Z9 12 U1 1 U2 5 PU U B C PRESS PI BILBAO PA UNIV BASQUE COUNTRY, EDITORIAL SERVICES, PO BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 EI 1696-3547 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PY 2013 VL 57 IS 5 BP 365 EP 373 DI 10.1387/ijdb.120227h1 PG 9 WC Developmental Biology SC Developmental Biology GA AE1IL UT WOS:000333722900005 PM 23873368 ER PT J AU Kang, JX AF Kang, Jing X. TI Future Directions in Nutrition Research SO JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS LA English DT Editorial Material ID OMEGA-3-FATTY-ACIDS; VARIANTS; CANCER C1 [Kang, Jing X.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, Lab Lipid Med & Technol, 149,13th St,Room 4001, Charlestown, MA 02129 USA. EM kang.jing@mgh.harvard.edu NR 7 TC 0 Z9 0 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-6499 EI 1661-6758 J9 J NUTRIGENET NUTRIGE JI J. Nutrigenet. Nutrigenomics PY 2013 VL 6 IS 4-5 BP I EP III DI 10.1159/000357910 PG 3 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA AA5RW UT WOS:000331158300001 ER PT J AU Kearns, W Jasiewicz, JM Fozard, JL Webster, P Scott, S Craighead, J Bowen, ME McCarthy, J AF Kearns, William Jasiewicz, Jan M. Fozard, James L. Webster, Paul Scott, Steven Craighead, Jeffrey Bowen, Mary E. McCarthy, Joseph TI Temporo-spacial prompting for persons with cognitive impairment using smart wrist-worn interface SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Editorial Material ID TECHNOLOGY; ACCEPTANCE C1 [Kearns, William; Jasiewicz, Jan M.; Fozard, James L.; Scott, Steven; Craighead, Jeffrey] James A Haley Vet Hosp, Vet Integrated Serv Network 8, Ctr Innovat Disabil & Rehabil Res, Tampa, FL 33612 USA. [Kearns, William] Univ S Florida, Coll Behav & Community Sci, Dept Rehabil & Mental Hlth Counseling, Tampa, FL USA. [Fozard, James L.] Univ S Florida, Coll Behav & Community Sci, Sch Aging Studies, Tampa, FL USA. [Webster, Paul; McCarthy, Joseph] Ubisense, Cambridge, England. [Scott, Steven] James A Haley Vet Hosp, Phys Med & Rehabil Serv, Tampa, FL 33612 USA. [Bowen, Mary E.] W Chester Univ, Dept Hlth, W Chester, PA 19380 USA. [Bowen, Mary E.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Kearns, W (reprint author), James A Haley Vet Hosp, Vet Integrated Serv Network 8, Ctr Innovat Disabil & Rehabil Res, Tampa, FL 33612 USA. EM kearns@usf.edu RI Kearns, William/F-9810-2015 OI Kearns, William/0000-0002-0241-814X NR 13 TC 3 Z9 3 U1 0 U2 3 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 2013 VL 50 IS 10 BP VII EP XIII DI 10.1682/JRRD.2013.12.0261 PG 7 WC Rehabilitation SC Rehabilitation GA AE0LR UT WOS:000333658300001 PM 24699980 ER PT J AU Gebrosky, B Pearlman, J Cooper, RA Cooper, R Kelleher, A AF Gebrosky, Benjamin Pearlman, Jonathan Cooper, Rory A. Cooper, Rosemarie Kelleher, Annmarie TI Evaluation of lightweight wheelchairs using ANSI/RESNA testing standards SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE ANSI/RESNA; depot wheelchair; double drum; durability; fatigue tests; lightweight wheelchair; manual wheelchair; wheelchair; wheelchair comparison; wheelchair testing ID SPINAL-CORD-INJURY; MANUAL WHEELCHAIRS; ADVERSE CONSEQUENCES; REPAIRS; PEOPLE AB Lightweight wheelchairs are characterized by their low cost and limited range of adjustment. Our study evaluated three different folding lightweight wheelchair models using the American National Standards Institute/Rehabilitation Engineering Society of North America (ANSI/RESNA) standards to see whether quality had improved since the previous data were reported. On the basis of reports of increasing breakdown rates in the community, we hypothesized that the quality of these wheelchairs had declined. Seven of the nine wheelchairs tested failed to pass the multidrum test durability requirements. An average of 194,502 +/- 172,668 equivalent cycles was completed, which is similar to the previous test results and far below the 400,000 minimum required to pass the ANSI/RESNA requirements. This was also significantly worse than the test results for aluminum ultralight folding wheelchairs. Overall, our results uncovered some disturbing issues with these wheelchairs and suggest that manufacturers should put more effort into this category to improve quality. To improve the durability of lightweight wheelchairs, we suggested that stronger regulations be developed that require wheelchairs to be tested by independent and certified test laboratories. We also proposed a wheelchair rating system based on the National Highway Transportation Safety Administration vehicle crash ratings to assist clinicians and end users when comparing the durability of different wheelchairs. C1 [Gebrosky, Benjamin; Pearlman, Jonathan; Cooper, Rory A.; Cooper, Rosemarie; Kelleher, Annmarie] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Dept Vet Affairs VA, Rehabil Res & Dev Serv, Pittsburgh, PA 15206 USA. [Pearlman, Jonathan; Cooper, Rosemarie] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Cooper, Rory A.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. [Cooper, Rory A.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Cooper, Rosemarie; Kelleher, Annmarie] Univ Pittsburgh, Med Ctr, Ctr Assist Technol, Pittsburgh, PA USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151R B, 6425 Penn Ave,Suite 400, Pittsburgh, PA 15206 USA. EM rcooper@pitt.edu OI Pearlman, Jon/0000-0003-0830-9136 FU Center for Excellence for Wheelchairs and Associated Rehabilitation Engineering [B6789C] FX This material was based on work supported by the Center for Excellence for Wheelchairs and Associated Rehabilitation Engineering (grant B6789C). NR 22 TC 3 Z9 3 U1 2 U2 6 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 2013 VL 50 IS 10 BP 1373 EP 1389 DI 10.1682/JRRD.2012.08.0155 PG 17 WC Rehabilitation SC Rehabilitation GA AE0LR UT WOS:000333658300009 PM 24699973 ER PT B AU Mehta, DD Zanartu, M Van Stan, JH Feng, SW Cheyne, HA Hillman, RE AF Mehta, Daryush D. Zanartu, Matias Van Stan, Jarrad H. Feng, Shengran W. Cheyne, Harold A., II Hillman, Robert E. GP IEEE TI Smartphone-based detection of voice disorders by long-term monitoring of neck acceleration features SO 2013 IEEE INTERNATIONAL CONFERENCE ON BODY SENSOR NETWORKS (BSN) LA English DT Proceedings Paper CT IEEE International Conference on Body Sensor Networks CY MAY 06-09, 2013 CL MIT Media Lab, Cambridge, MA SP IEEE HO MIT Media Lab DE voice use; vocal hyperfunction; voice production model; accelerometer sensor; wearable voice sensor ID VIBRATION AB Many common voice disorders are chronic or recurring conditions that are likely to result from inefficient and/or abusive patterns of vocal behavior, termed vocal hyperfunction. Thus an ongoing goal in clinical voice assessment is the long-term monitoring of noninvasively derived measures to track hyperfunction. This paper reports on a smartphone-based voice health monitor that records the high-bandwidth accelerometer signal from the neck skin above the collarbone. Data collection is under way from patients with vocal hyperfunction and matched-control subjects to create a dataset designed to identify the best set of diagnostic measures for hyperfunctional patterns of vocal behavior. Vocal status is tracked from neck acceleration using previously-developed vocal dose measures and novel model-based features of glottal airflow estimates. Clinically, the treatment of hyperfunctional disorders would be greatly enhanced by the ability to unobtrusively monitor and quantify detrimental behaviors and, ultimately, to provide real-time biofeedback that could facilitate healthier voice use. C1 [Mehta, Daryush D.; Van Stan, Jarrad H.; Feng, Shengran W.; Hillman, Robert E.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. RP Mehta, DD (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. EM daryush.mehta@alum.mit.edu; matias.zanartu@usm.cl; jvanstan@mghihp.edu; willfeng@mit.edu; hac68@cornell.edu; hillman.robert@mgh.harvard.edu RI Emchi, Karma/Q-1952-2016 NR 22 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4799-0330-6; 978-1-4799-0331-3 PY 2013 PG 6 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BA2DO UT WOS:000333337600061 ER PT J AU Kang, JX AF Kang, Jing X. TI Nutrigenomics and Cancer Therapy SO JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS LA English DT Editorial Material ID METABOLISM; ROLES C1 [Kang, Jing X.] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, LLMT, 149,13th St,Room 4001, Charlestown, MA 02129 USA. EM kang.jing@mgh.harvard.edu NR 9 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-6499 EI 1661-6758 J9 J NUTRIGENET NUTRIGE JI J. Nutrigenet. Nutrigenomics PY 2013 VL 6 IS 3 BP I EP II DI 10.1159/000355340 PG 2 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 233TX UT WOS:000325593500001 ER PT S AU Mendonca, PRS Lamb, P Kriston, A Sasaki, K Kudo, M Sahani, DV AF Mendonca, Paulo R. S. Lamb, Peter Kriston, Andras Sasaki, Kosuke Kudo, Masayuki Sahani, Dushyant V. BE Mori, K Sakuma, I Sato, Y Barillot, C Navab, N TI Contrast-Independent Liver-Fat Quantification from Spectral CT Exams SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION (MICCAI 2013), PT I SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 16th International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) CY SEP 22-26, 2013 CL Nagoya Univ, Nagoya, JAPAN SP Nagoya Convent & Visitors Bur, Murata Sci Fdn, Daiko Fdn, Japan Soc Comp Aided Surg, Sci Council Japan, Nagoya Univ, Informat & Commun Headquarters, Nagoya Univ, Grad Sch Informat Sci HO Nagoya Univ ID COMPUTED-TOMOGRAPHY; STEATOSIS; MRI AB The diagnosis and treatment of fatty liver disease requires accurate quantification of the amount of fat in the liver. Image-based methods for quantification of liver fat are of increasing interest due to the high sampling error and invasiveness associated with liver biopsy, which despite these difficulties remains the gold standard. Current computed tomography (CT) methods for liver-fat quantification are only semi-quantitative and infer the concentration of liver fat heuristically. Furthermore, these techniques are only applicable to images acquired without the use of contrast agent, even though contrast-enhanced CT imaging is more prevalent in clinical practice. In this paper, we introduce a method that allows for direct quantification of liver fat for both contrast-free and contrast-enhanced CT images. Phantom and patient data are used for validation, and we conclude that our algorithm allows for highly accurate and repeatable quantification of liver fat for spectral CT. C1 [Mendonca, Paulo R. S.; Lamb, Peter] GE Global Res, One Res Circle, Niskayuna, NY 12309 USA. [Kriston, Andras] GE Co, Healthcare, H-6725 Szeged, Hungary. [Sasaki, Kosuke; Kudo, Masayuki] GE Co, Healthcare Japan, Hino, Tokyo, Japan. [Sahani, Dushyant V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mendonca, PRS (reprint author), GE Global Res, One Res Circle, Niskayuna, NY 12309 USA. EM mendonca@ge.com; peter.lamb@ge.com; a.kriston@ge.com; kosuke.sasaki@ge.com; masayuki.kudo@ge.com; dsahani@partners.org NR 13 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-642-40811-3; 978-3-642-40810-6 J9 LECT NOTES COMPUT SC PY 2013 VL 8149 BP 324 EP 331 PG 8 WC Computer Science, Artificial Intelligence; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BA2DH UT WOS:000333330700041 ER PT S AU Wu, PL Kang, W Al-Nayeem, A Sha, L Berlin, RB Goldman, JM AF Wu, Po-Liang Kang, Woochul Al-Nayeem, Abdullah Sha, Lui Berlin, Richard B., Jr. Goldman, Julian M. GP IEEE TI A Low Complexity Coordination Architecture for Networked Supervisory Medical Systems SO 2013 ACM/IEEE INTERNATIONAL CONFERENCE ON CYBER-PHYSICAL SYSTEMS (ICCPS) SE ACM-IEEE International Conference on Cyber-Physical Systems LA English DT Proceedings Paper CT 4th IEEE/ACM International Conference on Cyber-Physical Systems (ICCPS) CY APR 08-11, 2013 CL Philadelphia, PA SP IEEE, ACM DE Architectural patterns; networked supervisory medical systems; coordination; complexity reduction ID VERIFICATION AB Cooperating medical devices, envisioned by Integrated Clinical Environment (ICE) of Medical Device Plug-and-Play (MDPnP), is expected to improve the safety and the quality of patient care. To ensure safety, the cooperating medical devices must be thoroughly verified and tested. However, concurrent control of devices without proper coordination poses a significant challenge for the verification of the safety, since complex interaction patterns between devices might cause the explosion of the verification state space. In this paper, we propose a low-complexity coordination architecture and protocol for networked supervisory medical systems. The proposed architecture organizes the systems in a hierarchical and organ-based manner in accordance to human physiology and homeostasis. Further, the proposed protocol avoids potential conflicts and unsafe controls, while allowing efficient concurrent operations of medical devices. The evaluation results show that our approach reduce the complexity by several orders of magnitude. C1 [Wu, Po-Liang; Kang, Woochul; Al-Nayeem, Abdullah; Sha, Lui] Univ Illinois, Dept Comp Sci, Urbana, IL 61801 USA. [Berlin, Richard B., Jr.] Univ Illinois, Coll Med, Dept Comp Sci, Urbana, IL 61801 USA. [Goldman, Julian M.] Massachusetts Gen Hosp, Cambridge, MA USA. [Goldman, Julian M.] CIMIT, Cambridge, MA USA. RP Wu, PL (reprint author), Univ Illinois, Dept Comp Sci, Urbana, IL 61801 USA. EM wu87@illinois.edu; woochul@illinois.edu; aalnaye2@illinois.edu; lrs@illinois.edu; rberlin@illinois.edu; jgoldman@partners.org NR 27 TC 1 Z9 1 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2375-8317 BN 978-1-4503-1996-6 J9 ACM IEEE INT CONF CY PY 2013 BP 89 EP 98 PG 10 WC Computer Science, Hardware & Architecture; Computer Science, Information Systems SC Computer Science GA BA1RE UT WOS:000332951500010 ER PT S AU Wang, K Liu, TM Wu, J Horton, NG Lin, CP Xu, C AF Wang, Ke Liu, Tzu-Ming Wu, Juwell Horton, Nicholas G. Lin, Charles P. Xu, Chris BE Periasamy, A Konig, K So, PTC TI Multi-color femtosecond source for simultaneous excitation of multiple fluorescent proteins in two-photon fluorescence microscopy SO MULTIPHOTON MICROSCOPY IN THE BIOMEDICAL SCIENCES XIII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Multiphoton Microscopy in the Biomedical Sciences XIII CY FEB 03-05, 2013 CL San Francisco, CA SP SPIE, Becker & Hickel GmbH, Boston Elect Corp, Coherent, Inc, Intelligent Software Solut, Inc, JenLab GmbH, Newport Spectra Phys, Omega Opt, Inc, Princeton Instruments, Semrock, Inc, Carl Zeiss DE fluorescent protein; two-photon fluorescence microscopy; soliton self-frequency shift; large-mode-area fiber ID SELF-FREQUENCY SHIFT; SOLITON PULSE GENERATION; OPTICAL-FIBERS; SYSTEM; EXPRESSION; TRACKING; CELLS AB Simultaneous imaging of cells expressing multiple fluorescent proteins (FPs) is of particular interest in applications such as mapping neural circuits, tracking multiple immune cell populations, etc. To visualize both in vivo and ex vivo tissue morphology and physiology at a cellular level deep within scattering tissues, two-photon fluorescence microscopy (2PM) is a powerful tool that has found wide applications. However, simultaneous imaging of multiple FPs with 2PM is greatly hampered by the lack of proper ultrafast lasers offering multi-color femtosecond pulses, each targeting the two-photon absorption peak of a different FP. Here we demonstrate simultaneous two-photon fluorescence excitation of RFP, YFP, and CFP in human melanoma cells engineered to express a "rainbow" pallet of colors, using a novel fiber-based source with energetic, three-color femtosecond pulses. The three-color pulses, centered at 775 nm, 864 nm and 950 nm, are obtained through second harmonic generation of the 1550 nm pump laser and SHG of the solitons at 1728 nm and 1900 nm generated through soliton self-frequency shift (SSFS) of the pump laser in a large-mode-area (LMA) fiber. The resulting wavelengths are well matched to the two-photon absorption peaks of the three FPs for efficient excitation. Our results demonstrate that multi-color femtosecond pulse generation using SSFS and a turn-key, fiber-based femtosecond laser can fulfill the requirements for simultaneous imaging of multiple FPs in 2PM, opening new opportunities for a wide range of biological applications where non-invasive, high-resolution imaging of multiple fluorescent indicators is required. C1 [Wang, Ke; Horton, Nicholas G.; Xu, Chris] Cornell Univ, Sch Appl & Engn Phys, Ithaca, NY 14853 USA. [Liu, Tzu-Ming; Wu, Juwell; Lin, Charles P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Ctr Syst Biol, Boston, MA 02114 USA. [Liu, Tzu-Ming] Natl Taiwan Univ, Mol Imag Ctr, Inst Biomed Engn, Taipei 10617, Taiwan. RP Wang, K (reprint author), Cornell Univ, Sch Appl & Engn Phys, Ithaca, NY 14853 USA. EM charles_lin@hms.harvard.edu; chris.xu@cornell.edu NR 18 TC 1 Z9 1 U1 1 U2 6 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9357-6 J9 PROC SPIE PY 2013 VL 8588 AR UNSP 85882I DI 10.1117/12.2000583 PG 6 WC Engineering, Biomedical; Microscopy; Optics SC Engineering; Microscopy; Optics GA BFH45 UT WOS:000319872500052 ER PT J AU Pooler, AM Polydoro, M Wegmann, S Nicholls, SB Spires-Jones, TL Hyman, BT AF Pooler, Amy M. Polydoro, Manuela Wegmann, Susanne Nicholls, Samantha B. Spires-Jones, Tara L. Hyman, Bradley T. TI Propagation of tau pathology in Alzheimer's disease: identification of novel therapeutic targets SO ALZHEIMERS RESEARCH & THERAPY LA English DT Review ID PRION-LIKE PROPAGATION; CEREBROSPINAL-FLUID; MOUSE MODEL; EXTRACELLULAR TAU; ENDOGENOUS TAU; NEURODEGENERATIVE DISEASES; NEUROFIBRILLARY TANGLES; PASSIVE-IMMUNIZATION; PLASMA-MEMBRANE; NEURONAL CELLS AB Accumulation and aggregation of the microtubule-associated protein tau are a pathological hallmark of neurodegenerative disorders such as Alzheimer's disease (AD). In AD, tau becomes abnormally phosphorylated and forms inclusions throughout the brain, starting in the entorhinal cortex and progressively affecting additional brain regions as the disease progresses. Formation of these inclusions is thought to lead to synapse loss and cell death. Tau is also found in the cerebrospinal fluid (CSF), and elevated levels are a biomarker for AD. Until recently, it was thought that the presence of tau in the CSF was due to the passive release of aggregated tau from dead or dying tangle-bearing neurons. However, accumulating evidence from different AD model systems suggests that tau is actively secreted and transferred between synaptically connected neurons. Transgenic mouse lines with localized expression of aggregating human tau in the entorhinal cortex have demonstrated that, as these animals age, tau becomes mislocalized from axons to cell bodies and dendrites and that human tau-positive aggregates form first in the entorhinal cortex and later in downstream projection targets. Numerous in vitro and in vivo studies have provided insight into the mechanisms by which tau may be released and internalized by neurons and have started to provide insight into how tau pathology may spread in AD. In this review, we discuss the evidence for regulated tau release and its specific uptake by neurons. Furthermore, we identify possible therapeutic targets for preventing the propagation of tau pathology, as inhibition of tau transfer may restrict development of tau tangles in a small subset of neurons affected in early stages of AD and therefore prevent widespread neuron loss and cognitive dysfunction associated with later stages of the disease. C1 [Pooler, Amy M.; Polydoro, Manuela; Wegmann, Susanne; Nicholls, Samantha B.; Spires-Jones, Tara L.; Hyman, Bradley T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. [Pooler, Amy M.] Kings Coll London, Inst Psychiat, Dept Neurosci, London SE5 8AF, England. RP Hyman, BT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 114 16th St, Charlestown, MA 02129 USA. EM bhyman@partners.org OI Spires-Jones, Tara/0000-0003-2530-0598 FU American Health Assistance Foundation; Alzheimer's Research UK; Deutsche Forschungsgemeinschaft (DFG); [R00AG033670]; [R01AG026249-07]; [5T32AG00022222]; [R21 NS067127] FX This work was supported by R00AG033670, R01AG026249-07, 5T32AG00022222, and R21 NS067127 and grants from the American Health Assistance Foundation, Alzheimer's Research UK, and the Deutsche Forschungsgemeinschaft (DFG). NR 64 TC 15 Z9 15 U1 2 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-9193 J9 ALZHEIMERS RES THER JI Alzheimers Res. Ther. PY 2013 VL 5 IS 5 AR 49 DI 10.1186/alzrt214 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA AC0JL UT WOS:000332180500003 PM 24152385 ER PT S AU Lee, SW Fried, SI AF Lee, Seung Woo Fried, Shelley I. GP IEEE TI Magnetic Stimulation of Subthalamic Nucleus Neurons using Micro-coils for Deep Brain Stimulation SO 2013 6TH INTERNATIONAL IEEE/EMBS CONFERENCE ON NEURAL ENGINEERING (NER) SE International IEEE EMBS Conference on Neural Engineering LA English DT Proceedings Paper CT 6th International IEEE EMBS Conference on Neural Engineering (NER) CY NOV 06-08, 2013 CL San Diego, CA SP IEEE EMBS, Battelle, Brain Vis LLC, Cortech Solut, Univ Minnesota, IGERT Program, Syst Neuroengineering, IOP Publishing, Ripple, Univ Minnesota, Inst Engn Med, Plexon AB Recently micro-magnetic stimulation (mu MS) with sub-millimeter coils has been successfully used to stimulate retinal neurons in vitro. This raises the possibility that such coils could be used in a wide range of neural prosthetics, as they may provide a safer alternative to direct electrical stimulation. However, the ability of mu MS to modulate the neuronal activity of brain neurons has not been studied. Here we show that mu MS strongly modulates the neural activity of subthalamic nucleus (STN) neurons in vitro. Cell attached patch clamp was used to record neural activity in response to both pulsatile and sinusoidal waveforms. Pulsatile stimulation was not very effective but continuous presentation of low-frequency (500Hz) sinusoidal bursts of mu MS silenced STN neurons. This work supports further investigation of mu MS as an alternative to existing electrically-based DBS systems. C1 [Lee, Seung Woo; Fried, Shelley I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. RP Lee, SW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, MGH Thier 415,50 Blossom St, Boston, MA 02114 USA. EM Lee.Seungwoo@mgh.harvard.edu; Fried.Shelley@mgh.harvard.edu NR 5 TC 2 Z9 2 U1 1 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1948-3546 BN 978-1-4673-1969-0 J9 I IEEE EMBS C NEUR E PY 2013 BP 133 EP 135 PG 3 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA BA0HI UT WOS:000331259200034 ER PT S AU Prerau, MJ Purdon, PL AF Prerau, Michael J. Purdon, Patrick L. GP IEEE TI A Probabilistic Framework for Time-Frequency Detection of Burst Suppression SO 2013 6TH INTERNATIONAL IEEE/EMBS CONFERENCE ON NEURAL ENGINEERING (NER) SE International IEEE EMBS Conference on Neural Engineering LA English DT Proceedings Paper CT 6th International IEEE EMBS Conference on Neural Engineering (NER) CY NOV 06-08, 2013 CL San Diego, CA SP IEEE EMBS, Battelle, Brain Vis LLC, Cortech Solut, Univ Minnesota, IGERT Program, Syst Neuroengineering, IOP Publishing, Ripple, Univ Minnesota, Inst Engn Med, Plexon ID EEG AB General anesthesia is a drug-induced, reversible condition comprised of hypnosis, amnesia, analgesia, akinesia, and autonomic stability. During the deepest levels of anesthesia, burst suppression is observed in the EEG, which consists of alternating periods of bursting and isoelectric activity. By accurately tracking anesthesia-induced burst suppression, it may be possible to provide a higher level of care for patients receiving general anesthesia. We develop a probabilistic framework for detecting burst suppression events. The algorithm uses multinomial regression to estimate the probability of burst, suppression, and artifact states at each time given EEG frequency-domain data. We test the efficacy of this method on clinical EEG acquired during operating room surgery with GA under propofol. C1 [Prerau, Michael J.; Purdon, Patrick L.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA 02129 USA. RP Prerau, MJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 149 13th St, Charlestown, MA 02129 USA. EM prerau@nmr.mgh.harvard.edu; patrickp@nmr.mgh.harvard.edu NR 9 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1948-3546 BN 978-1-4673-1969-0 J9 I IEEE EMBS C NEUR E PY 2013 BP 609 EP 612 PG 4 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA BA0HI UT WOS:000331259200153 ER PT S AU Bonmassar, G Serano, P Angelone, LM AF Bonmassar, Giorgio Serano, Peter Angelone, Leonardo M. GP IEEE TI Specific Absorption Rate in a Standard Phantom Containing a Deep Brain Stimulation Lead at 3 Tesla MRI. SO 2013 6TH INTERNATIONAL IEEE/EMBS CONFERENCE ON NEURAL ENGINEERING (NER) SE International IEEE EMBS Conference on Neural Engineering LA English DT Proceedings Paper CT 6th International IEEE EMBS Conference on Neural Engineering (NER) CY NOV 06-08, 2013 CL San Diego, CA SP IEEE EMBS, Battelle, Brain Vis LLC, Cortech Solut, Univ Minnesota, IGERT Program, Syst Neuroengineering, IOP Publishing, Ripple, Univ Minnesota, Inst Engn Med, Plexon ID SIMULATION; BIRDCAGE; SAFETY; COILS; WIRES; FIELD AB Finite elements methods (FEM) simulations are presented showing the specific absorption rate (SAR) distribution in the case of a Deep Brain Stimulation (DBS) lead inside a standard phantom exposed to 128 MHz / 3 Tesla magnetic resonance imaging (MRI). The electromagnetic model is proposed as a tool to study the safety of patients with an implanted DBS lead undergoing clinical 3T MRI systems. The simulations were based on an electromagnetic and circuit cosimulation methodology and allowed for fine tuning of the MRI radiofrequency transmit body coil. Results show that the presence of the lead did not influence the behavior of the coil, namely the S-parameters at the coil feed were largely unaffected by the presence of a lead. Conversely, significant changes of electric and magnetic field, as well as local SAR were observed due to the characteristic antenna effect. The lead path strongly affected the level of SAR at the distal tip of the lead, with a 10x fold difference between the two configurations evaluated. C1 [Bonmassar, Giorgio; Serano, Peter] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. [Angelone, Leonardo M.] US FDA, Ctr devices & Radiol Hlth, Div Phys, Of Sci & Engn Labs, Silver Spring, MD 20993 USA. RP Bonmassar, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. EM giorgio@nmr.mgh.harvard.edu; serano@nmr.mgh.harvard.edu; leonardo.angelone@fda.hhs.gov OI Angelone, Leonardo/0000-0002-1105-021X FU National Institutes of Health [U01-NS075026 (NINDS)] FX Research supported by the National Institutes of Health grant U01-NS075026 (NINDS). NR 26 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1948-3546 BN 978-1-4673-1969-0 J9 I IEEE EMBS C NEUR E PY 2013 BP 747 EP 750 PG 4 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA BA0HI UT WOS:000331259200185 ER PT J AU Ait-Aoudia, M Levy, PP Bui, E Insana, S de Fouchier, C Germain, A Jehel, L AF Ait-Aoudia, Malik Levy, Pierre P. Bui, Eric Insana, Salvatore de Fouchier, Capucine Germain, Anne Jehel, Louis TI Validation of the French version of the Pittsburgh Sleep Quality Index Addendum for posttraumatic stress disorder SO EUROPEAN JOURNAL OF PSYCHOTRAUMATOLOGY LA English DT Article DE Nightmares; posttraumatic sleep disturbances; trauma-related disorders; PTSD; psychometric properties ID IMAGERY REHEARSAL THERAPY; SEXUAL ASSAULT SURVIVORS; CHRONIC NIGHTMARES; MILITARY VETERANS; PSQI-A; PTSD; DISTURBANCES; INSOMNIA; TRIAL; SCALE AB Background: Sleep disturbances are one of the main complaints of patients with trauma-related disorders. The original Pittsburgh Sleep Quality Index Addendum for PTSD (PSQI-A) is self-report instrument developed to evaluate posttraumatic stress disorder (PTSD)-specific sleep disturbances in trauma-exposed individuals. However, to date, the PSQI-A has not yet been translated nor validated in French. Objective: The present study aims to: a) translate the PSQI-A into French, and b) examine its psychometric properties. Method: Seventy-three adult patients (mean age = 40.3 [SD = 15.0], 75% females) evaluated in a specialized psychotraumatology unit completed the French versions of the PSQI-A, Pittsburgh Sleep Quality Index (PSQI), Hospital Anxiety and Depression Scale (HADS), and Impact Event Scale-Revised (IES-R). Results: The French version of the PSQI-A showed satisfactory internal consistency, inter-item correlations, item correlations with the total score, convergent validity with PTSD and anxiety measures, and divergent validity with a depression measure. Conclusion: Our findings support the use of the French version of the PSQI-A for both clinical care and research. The French version of the PSQI-A is an important addition to the currently available instruments that can be used to examine trauma-related sleep disturbances among French-speaking individuals. C1 [Ait-Aoudia, Malik; de Fouchier, Capucine] Inst Victimol, Ctr Psychotrauma, F-75017 Paris, France. [Ait-Aoudia, Malik; de Fouchier, Capucine] Univ Paris 08, Lab Psychopathol & Neuropsychol EA 2027, F-93526 St Denis 02, France. [Ait-Aoudia, Malik] Ctr Hospitalier Univ Tenon, AP HP, Unite Psychiatrie & Psychotraumatol, Paris, France. [Levy, Pierre P.] Ctr Hospitalier Univ Tenon, AP HP, Dept Sante Publ, Paris, France. [Levy, Pierre P.] INSERM, U707, Paris, France. [Levy, Pierre P.] Univ Paris 06, UMR S 707, Paris, France. [Bui, Eric] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Bui, Eric] Univ Toulouse, LST, Toulouse, France. [Bui, Eric] CHU Toulouse, Toulouse, France. [Germain, Anne] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. [Jehel, Louis] Matin Univ Hosp CHUM Martin, Dept Psychiat & Psychotraumatol, Fort De France, Martinique. [Jehel, Louis] Univ Paris Sud, INSERM, Paris, France. [Jehel, Louis] Paris Descartes Univ, Paris, France. [Jehel, Louis] Lab Eth Med & Med Legale, Paris, France. RP Ait-Aoudia, M (reprint author), Inst Victimol, Ctr Psychotrauma, 131 Rue Saussure, F-75017 Paris, France. EM aitaoudia.malik@yahoo.fr RI Bui, Eric/J-8347-2015 OI Bui, Eric/0000-0002-1413-6473 NR 36 TC 1 Z9 2 U1 4 U2 6 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2000-8066 J9 EUR J PSYCHOTRAUMATO JI Eur. J. Psychotraumatol. PY 2013 VL 4 AR 19298 DI 10.3402/ejpt.v4i0.19298 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA AB9EZ UT WOS:000332094700001 PM 24044071 ER PT J AU Mileviciute, I Trujillo, J Gray, M Scott, WD AF Mileviciute, Inga Trujillo, John Gray, Matthew Scott, Walter D. TI THE ROLE OF EXPLANATORY STYLE AND NEGATIVE LIFE EVENTS IN DEPRESSION: A CROSS-SECTIONAL STUDY WITH YOUTH FROM A NORTH AMERICAN PLAINS RESERVATION SO AMERICAN INDIAN AND ALASKA NATIVE MENTAL HEALTH RESEARCH LA English DT Article ID ATTRIBUTIONAL STYLE; HOPELESSNESS THEORY; SELF-EFFICACY; SYMPTOMS; ADOLESCENTS; CHILDREN; ASSOCIATION; PERSPECTIVE; PREVALENCE; TRIBE AB In a cross-sectional study, we examined the role of explanatory styles and negative life events in the depressive experiences of AI youth. Ninety-three AI youth (49% female, ages 11-14 years) completed surveys assessing for explanatory style, negative life events, and depressive symptoms. Path analyses indicated that both the occurrence of negative life events within the past 6 months and a pessimistic explanatory style predicted more depressive symptoms. However, a moderation path model provided a superior fit to the data, indicating that the occurrence of negative life events was more strongly associated with depressive symptoms for those AI youth with a more pessimistic explanatory style. Findings are discussed in terms of potential interventions that can promote the well-being of this understudied and underserved population. C1 [Mileviciute, Inga; Scott, Walter D.] Univ Wyoming, Dept Psychol, Laramie, WY 82071 USA. [Gray, Matthew] Natl Ctr PTSD, Behav Sci Div, Boston, MA USA. RP Scott, WD (reprint author), Univ Wyoming, Dept Psychol, 1000 E Univ Ave, Laramie, WY 82071 USA. EM wscott@uwyo.edu NR 41 TC 1 Z9 1 U1 3 U2 7 PU UNIV PRESS COLORADO PI NIWOT PA PO BOX 849, NIWOT, CO 80544 USA SN 0893-5394 EI 1533-7731 J9 AM INDIAN ALASKA NAT JI Am. Indian Alsk. Nativ. Ment. Health Res. PY 2013 VL 20 IS 3 BP 42 EP 58 PG 17 WC Psychology, Clinical SC Psychology GA AB0CZ UT WOS:000331460700003 PM 24352819 ER PT J AU Jung, M AF Jung, Minsoo TI Cancer Control and the Communication Innovation in South Korea: Implications for Cancer Disparities SO ASIAN PACIFIC JOURNAL OF CANCER PREVENTION LA English DT Review DE Cancer control; information and communication technology; health communication; South Korea ID SERVICES TASK-FORCE; PREVENTION RECOMMENDATIONS; COMMUNICATIONS REVOLUTION; INFORMATION-SEEKING; PERCEIVED AMBIGUITY; PUBLIC-HEALTH; RISK; INEQUALITIES; PERCEPTIONS; FRAMEWORK AB Over the last 10 years, the number of cancer survivors in South Korea has reached nearly one million with a survival rate of 49.4%. However, integrated supportive care for cancer survivors is lagging. One area in which the current cancer control policy needs updating is in the utilization of information and communication technology (ICT). The remarkable progress in the field of ICT over the past 10 years presents exciting new opportunities for health promotion. Recent communication innovations are conducive to the exchange of meta-information, giving rise to a new service area and transforming patients into active medical consumers. Consequently, such innovations encourage active participation in the mutual utilization and sharing of high-quality information. However, these benefits from new ICTs will almost certainly not be equally available to all, leading to so-called communication inequalities where cancer survivors from lower socioeconomic classes will likely have more limited access to the best means of making use of the health information. Therefore, most essentially, emphasis must be placed on helping cancer survivors and their caregivers utilize such advances in ICT to create a more efficient flow of health information, thereby reducing communication inequalities and expanding social support. Once we enhance access to health information and better manage the quality of information, as a matter of fact, we can expect an alleviation of the health inequalities faced by cancer survivors. C1 [Jung, Minsoo] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Jung, Minsoo] Dongduk Womens Univ, Dept Hlth Sci, Seoul, South Korea. RP Jung, M (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. EM minsoo_jung@dfci.harvard.edu NR 59 TC 8 Z9 8 U1 1 U2 4 PU ASIAN PACIFIC ORGANIZATION CANCER PREVENTION PI GYEONGGI-DO PA APJCP HEAD OFFICE, KOREAN NATL CANCER CENTER, 323 ILAN -RO, ILSANDONG-GU, GOYANG-SI, GYEONGGI-DO, 410-769, SOUTH KOREA SN 1513-7368 J9 ASIAN PAC J CANCER P JI Asian Pac. J. Cancer Prev. PY 2013 VL 14 IS 6 BP 3411 EP 3417 DI 10.7314/APJCP.2013.14.6.3411 PG 7 WC Oncology SC Oncology GA AB0YG UT WOS:000331517700005 PM 23886120 ER PT B AU Yoshida, H AF Yoshida, Hiroyuki BE Friedrich, P Cycon, HL Clauss, J Wolf, B TI Cloud-super-computing virtual colonoscopy with motion-based navigation for colon cancer screening SO 2013 IEEE THIRD INTERNATIONAL CONFERENCE ON CONSUMER ELECTRONICS - BERLIN (ICCE-BERLIN) LA English DT Proceedings Paper CT IEEE 3rd Annual International Conference on Consumer Electronics - Berlin (ICCE-Berlin) CY SEP 08-11, 2013 CL Berlin, GERMANY SP IEEE, IEEE Consumer Elect Soc, VDE DE Cloud computing; high-performance computing; motion-based navigation; virtual colonoscopy; cancer screening ID TOMOGRAPHIC COLONOGRAPHY; ADENOMATOUS POLYPS; COLORECTAL-CANCER; RADIOLOGY AB A novel cloud-super-computing-based diagnostic system for colon cancer based on laxative-free virtual colonoscopy examination has been developed. The virtual colonoscopy images are post-processed by computationally intensive algorithms such as real-time computer-assisted bowel preparation for increased patient adherence to the screening program, and real-time computer-assisted detection for improved sensitivity in the detection of colonic polyps. A high-resolution mobile display system is connected to the cloud-supercomputing virtual colonoscopy system to allow for visualization of the entire colonic lumens and diagnosis of colonic lesions at anytime, anywhere. The navigation through the colonic lumen is driven by a motion-based natural user interface based on a Kinect sensor for easy navigation and localization of colonic lesions. Preliminary results show that the cloud-supercomputing-based virtual colonoscopy system with motion-based navigation improves the workflow and efficiency of the interpretation of virtual colonoscopy images for screening of colorectal cancers. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Yoshida, H (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM yoshida.hiro@mgh.harvard.edu NR 10 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4799-1412-8; 978-1-4799-1411-1 PY 2013 PG 3 WC Engineering, Electrical & Electronic SC Engineering GA BA0EN UT WOS:000331083000102 ER PT J AU Chapman, JAW Nielsen, TO Ellis, MJ Bernard, P Chia, S Gelmon, KA Pritchard, KI Le Maitre, A Goss, PE Leung, S Shepherd, LE Bramwell, VHC AF Chapman, Judith-Anne W. Nielsen, Torsten O. Ellis, Matthew J. Bernard, Phillip Chia, Stephen Gelmon, Karen A. Pritchard, Kathleen I. Le Maitre, Aurelie Goss, Paul E. Leung, Samuel Shepherd, Lois E. Bramwell, Vivien H. C. TI Effect of continuous statistically standardized measures of estrogen and progesterone receptors on disease-free survival in NCIC CTG MA.12 Trial and BC Cohort SO BREAST CANCER RESEARCH LA English DT Article ID PRIMARY BREAST-CANCER; PROTEIN EXPRESSION; IMMUNOHISTOCHEMICAL-DEMONSTRATION; PREDICTIVE FACTORS; PROGNOSTIC-FACTORS; TAMOXIFEN; SENSITIVITY; RECURRENCE; VALUES; WOMEN AB Introduction: We hypothesized improved inter-laboratory comparability of estrogen receptor (ER) and progesterone receptor (PgR) across different assay methodologies with adjunctive statistical standardization, akin to bone mineral density (BMD) z-scores. We examined statistical standardization in MA. 12, a placebo-controlled premenopausal trial of adjuvant tamoxifen with locally assessed hormone receptor +/- tumours, and in a cohort of post-menopausal British Columbia (BC) tamoxifen-treated patients. Methods: ER and PgR were centrally assessed for both patient groups with real time quantitative reverse transcription polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Effects on disease-free survival (DFS) were investigated separately for 345 MA. 12 and 673 BC patients who had both qPCR and IHC assessments. Comparisons utilized continuous laboratory units and statistically standardized z-scores. Univariate categorization of ER/PgR was by number of standard deviations (SD) above or below the mean (z-score >= 1.0 SD below mean; z-score <1.0 SD below mean; z-score >= 1.0 SD above mean; z-score >1.0 SD above mean). Exploratory multivariate examinations utilized step-wise Cox regression. Results: Median follow-up for MA. 12 was 9.7 years; for BC patients, 11.8 years. For MA. 12, 101 of 345 (29%) patients were IHC ER-PgR-. ER was not univariately associated with DFS (qPCR, P = 0.19; IHC, P = 0.08), while PgR was (qPCR, P = 0.09; IHC, P = 0.04). For BC patients, neither receptor was univariately associated with DFS: for ER, PCR, P = 0.36, IHC, P = 0.24; while for PgR, qPCR, P = 0.17, IHC, P = 0.31. Multivariately, MA. 12 patients randomized to tamoxifen had significantly better DFS (P = 0.002 to 0.005) than placebo. Meanwhile, jointly ER and PgR were not associated with DFS whether assessed by qPCR or by IHC in all patients, or in the subgroup of patients with IHC positive stain, for pooled or separate treatment arms. Different results by type of continuous unit supported the concept of ER level being relevant for medical decision-making. For postmenopausal BC tamoxifen patients, higher qPCR PgR was weakly associated with better DFS (P = 0.06). Conclusions: MA. 12 pre-menopausal patients in a placebo-controlled tamoxifen trial had similar multivariate prognostic effects with statistically standardized hormone receptors when tumours were assayed by qPCR or IHC, for hormone receptor +/- and + tumours. The BC post-menopausal tamoxifen cohort did not exhibit a significant prognostic association of ER or PgR with DFS. Adjunctive statistical standardization is currently under investigation in other NCIC CTG endocrine trials. C1 [Chapman, Judith-Anne W.; Le Maitre, Aurelie; Shepherd, Lois E.] Queens Univ, NCIC Clin Trials Grp, Kingston, ON K7L 3N6, Canada. [Nielsen, Torsten O.; Leung, Samuel] Univ British Columbia, Vancouver Hosp, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. [Ellis, Matthew J.] Washington Univ, Div Med Oncol, Sch Med, St Louis, MO 63110 USA. [Bernard, Phillip] Univ Utah, Dept Pathol, Salt Lake City, UT 84112 USA. [Chia, Stephen; Gelmon, Karen A.] BCCA Vancouver Ctr, Div Med Oncol, Vancouver, BC V5Z 4E6, Canada. [Pritchard, Kathleen I.] Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON M4N 3M5, Canada. [Goss, Paul E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bramwell, Vivien H. C.] Univ Calgary, Dept Oncol, Calgary, AB T2N 4N2, Canada. RP Chapman, JAW (reprint author), Queens Univ, NCIC Clin Trials Grp, Kingston, ON K7L 3N6, Canada. EM JChapman@ctg.queensu.ca FU Canadian Cancer Society through Canadian Cancer Society Research Institute; Queen's University; Avon Foundation in New York FX This work was supported by the Canadian Cancer Society through a grant from the Canadian Cancer Society Research Institute to the NCIC Clinical Trials Group, as well as by a Queen's University start-up grant to J.W. Chapman. Paul Goss is supported by the Avon Foundation in New York. We thank Christine Chow for technical assistance. NR 27 TC 3 Z9 3 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. PY 2013 VL 15 IS 4 AR R71 DI 10.1186/bcr3465 PG 13 WC Oncology SC Oncology GA AB1HV UT WOS:000331543000018 PM 23972025 ER PT J AU de Prost, N Costa, EL Wellman, T Musch, G Tucci, MR Winkler, T Harris, RS Venegas, JG Kavanagh, BP Melo, MFV AF de Prost, Nicolas Costa, Eduardo L. Wellman, Tyler Musch, Guido Tucci, Mauro R. Winkler, Tilo Harris, R. Scott Venegas, Jose G. Kavanagh, Brian P. Melo, Marcos F. Vidal TI Effects of ventilation strategy on distribution of lung inflammatory cell activity SO CRITICAL CARE LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; END-EXPIRATORY PRESSURE; POSITRON-EMISSION-TOMOGRAPHY; METABOLIC-ACTIVITY; TIDAL VOLUME; F-18-FDG PET; FDG-PET; MECHANICAL VENTILATION; PULMONARY INFLAMMATION; SURFACTANT DEPLETION AB Introduction: Leukocyte infiltration is central to the development of acute lung injury, but it is not known how mechanical ventilation strategy alters the distribution or activation of inflammatory cells. We explored how protective (vs. injurious) ventilation alters the magnitude and distribution of lung leukocyte activation following systemic endotoxin administration. Methods: Anesthetized sheep received intravenous endotoxin (10 ng/kg/min) followed by 2 h of either injurious or protective mechanical ventilation (n = 6 per group). We used positron emission tomography to obtain images of regional perfusion and shunting with infused N-13[nitrogen]-saline and images of neutrophilic inflammation with F-18-fluorodeoxyglucose (F-18-FDG). The Sokoloff model was used to quantify F-18-FDG uptake (K-i), as well as its components: the phosphorylation rate (k(3), a surrogate of hexokinase activity) and the distribution volume of F-18-FDG (F-e) as a fraction of lung volume (K-i = F-e x k(3)). Regional gas fractions (f(gas)) were assessed by examining transmission scans. Results: Before endotoxin administration, protective (vs. injurious) ventilation was associated with a higher ratio of partial pressure of oxygen in arterial blood to fraction of inspired oxygen (PaO2/FiO(2)) (351 +/- 117 vs. 255 +/- 74 mmHg; P < 0.01) and higher whole-lung f(gas) (0.71 +/- 0.12 vs. 0.48 +/- 0.08; P = 0.004), as well as, in dependent regions, lower shunt fractions. Following 2 h of endotoxemia, PaO2/FiO(2) ratios decreased in both groups, but more so with injurious ventilation, which also increased the shunt fraction in dependent lung. Protective ventilation resulted in less nonaerated lung (20-fold; P < 0.01) and more normally aerated lung (14-fold; P < 0.01). K-i was lower during protective (vs. injurious) ventilation, especially in dependent lung regions (0.0075 +/- 0.0043/min vs. 0.0157 +/- 0.0072/min; P < 0.01). F-18-FDG phosphorylation rate (k(3)) was twofold higher with injurious ventilation and accounted for most of the between-group difference in K-i. Dependent regions of the protective ventilation group exhibited lower k(3) values per neutrophil than those in the injurious ventilation group (P = 0.01). In contrast, F-e was not affected by ventilation strategy (P = 0.52). Lung neutrophil counts were not different between groups, even when regional inflation was accounted for. Conclusions: During systemic endotoxemia, protective ventilation may reduce the magnitude and heterogeneity of pulmonary inflammatory cell metabolic activity in early lung injury and may improve gas exchange through its effects predominantly in dependent lung regions. Such effects are likely related to a reduction in the metabolic activity, but not in the number, of lung-infiltrating neutrophils. C1 [de Prost, Nicolas; Costa, Eduardo L.; Wellman, Tyler; Musch, Guido; Tucci, Mauro R.; Winkler, Tilo; Venegas, Jose G.; Melo, Marcos F. Vidal] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Harris, R. Scott] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA 02114 USA. [Kavanagh, Brian P.] Univ Toronto, Hosp Sick Children, Dept Crit Care, Toronto, ON M5G 1X8, Canada. [Kavanagh, Brian P.] Univ Toronto, Hosp Sick Children, Dept Anesthesia, Toronto, ON M5G 1X8, Canada. RP Melo, MFV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM mvidalmelo@partners.org RI Winkler, Tilo/B-5337-2009; OI Winkler, Tilo/0000-0002-7276-5550; de Prost, Nicolas/0000-0002-4833-4320 FU National Heart, Lung, and Blood Institute (NHLBI) [5R01-HL086827, 5K08HL076464]; Societe de Pneumologie de Langue Francaise (SPLF) FX The authors thank Dr Sandrine Katsahian for statistical assistance. This work was supported by National Heart, Lung, and Blood Institute (NHLBI) grant 5R01-HL086827. GM received salary support from NHLBI grant 5K08HL076464. NP received a scholarship from the Societe de Pneumologie de Langue Francaise (SPLF). NR 68 TC 11 Z9 11 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X EI 1364-8535 J9 CRIT CARE JI Crit. Care PY 2013 VL 17 IS 4 AR R175 DI 10.1186/cc12854 PG 12 WC Critical Care Medicine SC General & Internal Medicine GA AB1GO UT WOS:000331539700048 PM 23947920 ER PT J AU Johnson, DW Schmidt, UH Bittner, EA Christensen, B Levi, R Pino, RM AF Johnson, Daniel W. Schmidt, Ulrich H. Bittner, Edward A. Christensen, Benjamin Levi, Retsef Pino, Richard M. TI Delay of transfer from the intensive care unit: a prospective observational study of incidence, causes, and financial impact SO CRITICAL CARE LA English DT Article DE critical care utilization; cost analysis; triage; resource allocation; organizational efficiency; workflow AB Introduction: A paucity of literature exists regarding delays in transfer out of the intensive care unit. We sought to analyze the incidence, causes, and costs of delayed transfer from a surgical intensive care unit (SICU). Methods: An IRB-approved prospective observational study was conducted from January 24, 2010, to July 31, 2010, of all 731 patients transferred from a 20-bed SICU at a large tertiary-care academic medical center. Data were collected on patients who were medically ready for transfer to the floor who remained in the SICU for at least 1 extra day. Reasons for delay were examined, and extra costs associated were estimated. Results: Transfer to the floor was delayed in 22% (n = 160) of the 731 patients transferred from the SICU. Delays ranged from 1 to 6 days (mean, 1.5 days; median, 2 days). The extra costs associated with delays were estimated to be $581,790 during the study period, or $21,547 per week. The most common reasons for delay in transfer were lack of available surgical-floor bed (71% (114 of 160)), lack of room appropriate for infectious contact precautions (18% (28 of 160)), change of primary service (Surgery to Medicine) (7% (11 of 160)), and lack of available patient attendant ("sitter" for mildly delirious patients) (3% (five of 160)). A positive association was found between the daily hospital census and the daily number of SICU beds occupied by patients delayed in transfer (Spearman rho = 0.27; P < 0.0001). Conclusions: Delay in transfer from the SICU is common and costly. The most common reason for delay is insufficient availability of surgical-floor beds. Delay in transfer is associated with high hospital census. Further study of this problem is necessary. C1 [Johnson, Daniel W.] Univ Nebraska Med Ctr, Dept Anesthesiol, Omaha, NE 68198 USA. [Schmidt, Ulrich H.; Bittner, Edward A.; Pino, Richard M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Christensen, Benjamin; Levi, Retsef] MIT, Alfred P Sloan Sch Management, Cambridge, MA 02142 USA. RP Johnson, DW (reprint author), Univ Nebraska Med Ctr, Dept Anesthesiol, 984455 Nebraska Med Ctr, Omaha, NE 68198 USA. EM danielwj77@gmail.com FU Department of Anesthesia, Critical Care and Pain Medicine at the Massachusetts General Hospital; Department of Anesthesia, Critical Care & Pain Medicine, Massachusetts General Hospital FX We thank the nursing staff of the SICU at Massachusetts General Hospital for their assistance with data collection during the study period. The source of all funding for the entire study was the Department of Anesthesia, Critical Care and Pain Medicine at the Massachusetts General Hospital. The study was supported by the Department of Anesthesia, Critical Care & Pain Medicine, Massachusetts General Hospital. No extramural funding was used to support the study. NR 16 TC 8 Z9 8 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X EI 1364-8535 J9 CRIT CARE JI Crit. Care PY 2013 VL 17 IS 4 AR R128 DI 10.1186/cc12807 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA AB1GO UT WOS:000331539700002 PM 23826830 ER PT J AU Oto, J Li, Q Kimball, WR Wang, JP Sabouri, AS Harrell, PG Kacmarek, RM Jiang, YD AF Oto, Jun Li, Qian Kimball, William R. Wang, Jingping Sabouri, Abdolnabi S. Harrell, Priscilla G. Kacmarek, Robert M. Jiang, Yandong TI Continuous positive airway pressure and ventilation are more effective with a nasal mask than a full face mask in unconscious subjects: a randomized controlled trial SO CRITICAL CARE LA English DT Article ID OBSTRUCTIVE SLEEP-APNEA; GENERAL-ANESTHESIA; PROPOFOL ANESTHESIA; INDUCTION; COLLAPSIBILITY; RESUSCITATION; INFANTS; PATENCY; CARE AB Introduction: Upper airway obstruction (UAO) is a major problem in unconscious subjects, making full face mask ventilation difficult. The mechanism of UAO in unconscious subjects shares many similarities with that of obstructive sleep apnea (OSA), especially the hypotonic upper airway seen during rapid eye movement sleep. Continuous positive airway pressure (CPAP) via nasal mask is more effective at maintaining airway patency than a full face mask in patients with OSA. We hypothesized that CPAP via nasal mask and ventilation (nCPAP) would be more effective than full face mask CPAP and ventilation (FmCPAP) for unconscious subjects, and we tested our hypothesis during induction of general anesthesia for elective surgery. Methods: In total, 73 adult subjects requiring general anesthesia were randomly assigned to one of four groups: nCPAP P0, nCPAP P5, FmCPAP P0, and FmCPAP P5, where P0 and P5 represent positive end-expiratory pressure (PEEP) 0 and 5 cm H2O applied prior to induction. After apnea, ventilation was initiated with pressure control ventilation at a peak inspiratory pressure over PEEP (PIP/PEEP) of 20/0, then 20/5, and finally 20/10 cm H2O, each applied for 1 min. At each pressure setting, expired tidal volume (Vte) was calculated by using a plethysmograph device. Results: The rate of effective tidal volume (Vte > estimated anatomical dead space) was higher (87.9% vs. 21.9%; P<0.01) and the median Vte was larger (6.9 vs. 0 mL/kg; P<0.01) with nCPAP than with FmCPAP. Application of CPAP prior to induction of general anesthesia did not affect Vte in either approach (nCPAP pre-vs. post-; 7.9 vs. 5.8 mL/kg, P = 0.07) (FmCPAP pre-vs. post-; 0 vs. 0 mL/kg, P = 0.11). Conclusions: nCPAP produced more effective tidal volume than FmCPAP in unconscious subjects. C1 [Oto, Jun; Li, Qian; Kimball, William R.; Wang, Jingping; Sabouri, Abdolnabi S.; Harrell, Priscilla G.; Jiang, Yandong] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Li, Qian] Sichuan Univ, Dept Anesthesia, West China Hosp, Chengdu 610041, Sichuan, Peoples R China. [Oto, Jun; Kacmarek, Robert M.] Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA. RP Jiang, YD (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM yjiang@partners.org FU Covidien FX RMK is a consultant for Covidien (Dublin, Ireland), has received research grants from Covidien, and has received honorarium for lecturing from Maquet (Rastatt, Germany). The other authors declare that they have no competing interests. NR 29 TC 8 Z9 8 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X EI 1364-8535 J9 CRIT CARE JI Crit. Care PY 2013 VL 17 IS 6 AR R300 DI 10.1186/cc13169 PG 11 WC Critical Care Medicine SC General & Internal Medicine GA AB1HQ UT WOS:000331542500037 PM 24365207 ER PT J AU Skibsted, S Bhasin, MK Aird, WC Shapiro, NI AF Skibsted, Simon Bhasin, Manoj K. Aird, William C. Shapiro, Nathan I. TI Bench-to-bedside review: Future novel diagnostics for sepsis - a systems biology approach SO CRITICAL CARE LA English DT Review ID SEPTIC SHOCK SUSCEPTIBILITY; ACUTE LUNG INJURY; HUMAN-DISEASES; HUMAN GENOME; CIRCULATING MICRORNAS; GENETIC POLYMORPHISMS; WIDE ASSOCIATION; PLASMA PROTEOME; MICROARRAY DATA; CANCER AB The early, accurate diagnosis and risk stratification of sepsis remains an important challenge in the critically ill. Since traditional biomarker strategies have not yielded a gold standard marker for sepsis, focus is shifting towards novel strategies that improve assessment capabilities. The combination of technological advancements and information generated through the human genome project positions systems biology at the forefront of biomarker discovery. While previously available, developments in the technologies focusing on DNA, gene expression, gene regulatory mechanisms, protein and metabolite discovery have made these tools more feasible to implement and less costly, and they have taken on an enhanced capacity such that they are ripe for utilization as tools to advance our knowledge and clinical research. Medicine is in a genome-level era that can leverage the assessment of thousands of molecular signals beyond simply measuring selected circulating proteins. Genomics is the study of the entire complement of genetic material of an individual. Epigenetics is the regulation of gene activity by reversible modifications of the DNA. Transcriptomics is the quantification of the relative levels of messenger RNA for a large number of genes in specific cells or tissues to measure differences in the expression levels of different genes, and the utilization of patterns of differential gene expression to characterize different biological states of a tissue. Proteomics is the large-scale study of proteins. Metabolomics is the study of the small molecule profiles that are the terminal downstream products of the genome and consists of the total complement of all low-molecular-weight molecules that cellular processes leave behind. Taken together, these individual fields of study may be linked during a systems biology approach. There remains a valuable opportunity to deploy these technologies further in human research. The techniques described in this paper not only have the potential to increase the spectrum of diagnostic and prognostic biomarkers in sepsis, but they may also enable the discovery of new disease pathways. This may in turn lead us to improved therapeutic targets. The objective of this paper is to provide an overview and basic framework for clinicians and clinical researchers to better understand the 'omics technologies' to enhance further use of these valuable tools. C1 [Skibsted, Simon; Shapiro, Nathan I.] Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. [Skibsted, Simon; Aird, William C.; Shapiro, Nathan I.] Beth Israel Deaconess Med Ctr, Vasc Biol Res Ctr, Boston, MA 02215 USA. [Skibsted, Simon; Shapiro, Nathan I.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Bhasin, Manoj K.] Beth Israel Deaconess Med Ctr Genom & Core, Boston, MA 02115 USA. RP Skibsted, S (reprint author), Beth Israel Deaconess Med Ctr, Dept Emergency Med, 330 Brookline Ave, Boston, MA 02215 USA. EM sskibste@bidmc.harvard.edu RI Shapiro, Nathan/F-1718-2016 FU Aarhus University, Denmark; National Institutes of Health [GM076659, SR01HL093234-02, HL091757, GM088184] FX SS is funded by a research grant from Aarhus University, Denmark. NIS is funded in part by National Institutes of Health grants HL091757, GM076659, and SR01HL093234-02. WCA is supported by National Institutes of Health grants HL091757 and GM088184. NR 96 TC 18 Z9 18 U1 2 U2 17 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X EI 1364-8535 J9 CRIT CARE JI Crit. Care PY 2013 VL 17 IS 5 AR 231 DI 10.1186/cc12693 PG 15 WC Critical Care Medicine SC General & Internal Medicine GA AB1HA UT WOS:000331540900101 PM 24093155 ER PT J AU Tobin, MJ AF Tobin, Martin J. TI Probing with the ventilator SO CRITICAL CARE LA English DT Editorial Material ID MECHANICAL VENTILATION; TRIALS AB Neurally adjusted ventilatory assist operates through recordings of electrical activity of the diaphragm (EAdi). Barwing and colleagues found increases in EAdi in weaning-failure patients, although the values were not significantly different from weaning-success patients. Future studies will need to carefully control for the considerable biological noise evident in EAdi recordings. C1 [Tobin, Martin J.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. [Tobin, Martin J.] Loyola Univ, Chicago Stritch Sch Med, Hines, IL 60141 USA. RP Tobin, MJ (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. EM mtobin2@lumc.edu NR 7 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X EI 1364-8535 J9 CRIT CARE JI Crit. Care PY 2013 VL 17 IS 5 AR 198 DI 10.1186/cc13038 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA AB1HA UT WOS:000331540900099 PM 24090345 ER PT S AU Vinegoni, C Siegel, C Mlynarchik, A Sena, BF de Abreu, LC Lima, JL Figueiredo, JL AF Vinegoni, Claudio Siegel, Cory Mlynarchik, Andrew Sena, Brena Figueiredo de Abreu, Luiz Carlos Lima Filho, Jose Luiz Figueiredo, Jose-Luiz BE Kokudo, N Ishizawa, T TI Novel Fluorescent Probes for Intraoperative Cholangiography SO FLUORESCENT IMAGING: TREATMENT OF HEPATOBILIARY AND PANCREATIC DISEASES SE Frontiers of Gastrointestinal Research LA English DT Article; Book Chapter ID EXTRAHEPATIC BILE-DUCTS; INDOCYANINE GREEN; LAPAROSCOPIC CHOLECYSTECTOMY; BILIARY ANATOMY; PREVENTION; IDENTIFICATION; SURGERY; INJURY AB Intraoperative fluorescence optical imaging of the biliary ducts has been recently shown to be an effective and economically viable imaging methodology for the prevention of biliary injury. While the exploitation of fluorescence imaging during biliary surgeries may still be relatively new, recent efforts have been made toward the development of novel near-infrared (NIR) optical imaging contrast agents with the goal to reduce unwanted intraoperative occurrences. The focus of this chapter is centered on the exploration of novel types of biliary-excreted contrast agents aimed at improving the current state of fluorescence cholangiography. Copyright (C) 2013 S. Karger AG, Basel C1 [Vinegoni, Claudio; Sena, Brena Figueiredo] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Vinegoni, Claudio; Sena, Brena Figueiredo] Harvard Univ, Sch Med, Boston, MA USA. [Siegel, Cory] Boston Med Ctr, Dept Radiol, Boston, MA USA. [Mlynarchik, Andrew; Figueiredo, Jose-Luiz] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [de Abreu, Luiz Carlos] ABC, Sch Med, Lab Sci Writing, Santo Andre, Brazil. [Lima Filho, Jose Luiz] Univ Fed Pernambuco, LIKA, Recife, PE, Brazil. RP Figueiredo, JL (reprint author), Brigham & Womens Hosp, CICS, Kowa Pharmaceut, 75 Francis St, Boston, MA 02115 USA. EM jlfigueiredo@partners.org OI de Abreu, Luiz Carlos/0000-0002-7618-2109 NR 25 TC 0 Z9 0 U1 0 U2 2 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0302-0665 BN 978-3-318-02293-3; 978-3-318-02292-6 J9 FRONT GASTROINT RES JI Front.Gastrointest.Res. PY 2013 VL 31 BP 106 EP 112 DI 10.1159/000348627 PG 7 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA BJR67 UT WOS:000329844500016 ER PT J AU Ni, T Wang, N Mao, ZG Yao, M AF Ni, T. Wang, N. Mao, Z. G. Yao, M. TI Identification of marker genes in diabetic wounds by DNA microarray study SO GENETICS AND MOLECULAR RESEARCH LA English DT Article DE Diabetic wounds; Module analysis; Phylogenetic analysis ID INTERACTION NETWORKS; EXPRESSION; CD44; FIBROBLASTS; CHEMOKINES; MELLITUS AB This study aimed to identify marker genes in diabetic wounds using a dataset based on a DNA microarray of dermal lymphatic endothelial cells, and our results provide a basic understanding of diabetic wounds through further study of these differentially expressed genes (DEGs). From the Gene Expression Omnibus database, we downloaded a gene expression microarray (GSE38396) that includes 8 samples: 4 normal controls and 4 disease samples (type II diabetes). We then identified genes that were differentially expressed between normal and disease samples using packages in R language, constructed a protein-protein interaction (PPI) network and analyzed modules in the network. In addition, phylogenetic analysis was performed by MEGA to find the most conserved genes. Two hundred and thirteen genes were identified as being differentially expressed between normal and disease samples, and we constructed a PPI network that included 213 pairs of proteins. We then identified a module including 20 genes, the function of which was significantly enriched in wounding response. Lastly, the most conserved genes, CD44 and CCL5, were identified through phylogenetic analysis. In summary, we found differentially expressed marker genes, a wounding response-related module, and the most important genes CD44 and CCL5. Our findings suggest new approaches to therapies for diabetic wounds. C1 [Ni, T.; Wang, N.; Mao, Z. G.; Yao, M.] Shanghai Jiao Tong Univ, Sch Med, Peoples Hosp 3, Dept Burn & Plast Surg, Shanghai 200030, Peoples R China. [Ni, T.; Wang, N.; Mao, Z. G.; Yao, M.] Shanghai Jiao Tong Univ, Sch Med, Inst Traumat Med, Shanghai 200030, Peoples R China. [Yao, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Yao, M (reprint author), Shanghai Jiao Tong Univ, Sch Med, Peoples Hosp 3, Dept Burn & Plast Surg, Shanghai 200030, Peoples R China. EM yaominyaomin268@gmail.com NR 30 TC 0 Z9 0 U1 0 U2 0 PU FUNPEC-EDITORA PI RIBEIRAO PRETO PA RUA FLORIANO PEIXOTO 2444, ALTO DA BOA VISTA, RIBEIRAO PRETO, SP 00000, BRAZIL SN 1676-5680 J9 GENET MOL RES JI Genet. Mol. Res. PY 2013 VL 12 IS 4 BP 5348 EP 5355 DI 10.4238/2013.November.7.9 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AB2FG UT WOS:000331608000123 PM 24301906 ER PT J AU Wang, LS Jiao, Y Huang, Y Liu, XY Gibson, G Bennett, B Hamre, KM Li, DW Zhao, HY Gelernter, J Kranzler, HR Farrer, LA Lu, L Wang, YJ Gu, WK AF Wang, L. S. Jiao, Y. Huang, Y. Liu, X. Y. Gibson, G. Bennett, B. Hamre, K. M. Li, D. W. Zhao, H. Y. Gelernter, J. Kranzler, H. R. Farrer, L. A. Lu, L. Wang, Y. J. Gu, W. K. TI Critical evaluation of transcription factor Atf2 as a candidate modulator of alcohol preference in mouse and human populations SO GENETICS AND MOLECULAR RESEARCH LA English DT Article DE Alcohol preference; Atf2; Candidate; QTL; Gene expression ID GENETIC DISSECTION; ETHANOL; TRAIT; EXPRESSION; STRAINS; METABOLISM; DEPENDENCE; KINASE AB In prior work, congenic strains carrying the DBA/2Igb (D2) region of chromosome 2 (Chr2) for alcohol preference were bred onto a C57BL/6Ibg (B6) background and as predicted were found to reduce voluntary consumption. Subsequently, interval-specific congenic recombinant strains (ISCRS) were generated and also tested. These ISCRS strains reduced the quantitative trait loci (QTL) interval to a comparatively small 3.4 Mb region. Here, we have exploited an integrative approach using both murine and human populations to critically evaluate candidate genes within this region. First, we used bioinformatics tools to search for genes relevant to alcohol preference within the QTL region. Second, we searched for single nucleotide polymorphisms (SNPs) within exons of every gene in this region. Third, we conducted follow-up microarray analyses to identify differentially expressed genes between the B6 and ISCRS strains in mice from each group. Fourth, we analyzed correlations between the expression level of candidate genes and phenotypes of alcohol preference in a large family of BXD recombinant inbred strains derived from B6 and D2. Finally, we evaluated SNP segregation in both BXD mouse strains and in humans who were heavy alcohol drinkers or non-drinkers. Among several potential candidate genes in this region, we identified activating transcription factor 2 (Atf2) as the most plausible gene that would influence alcohol preference. However, the candidacy of Atf2 was only weakly supported when we used a genetic network approach and by focused reanalysis of genome-wide association study data from European-American and African-American populations. Thus, we cannot conclude that Atf2 plays a role in the regulation of the QTL of mouse Chr2. C1 [Wang, L. S.; Jiao, Y.; Huang, Y.; Liu, X. Y.; Gibson, G.; Gu, W. K.] Univ Tennessee, Ctr Hlth Sci, Campbell Clin, Dept Orthopaed Surg & BioMed Engn, Memphis, TN 38163 USA. [Bennett, B.] Univ Colorado Denver, Sch Pharm, Aurora, CO USA. [Hamre, K. M.; Lu, L.] Univ Tennessee, Ctr Hlth Sci, Dept Anat & Neurobiol, Memphis, TN 38163 USA. [Li, D. W.; Gelernter, J.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Zhao, H. Y.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. [Zhao, H. Y.; Gelernter, J.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Gelernter, J.] VA Connecticut Healthcare Ctr, West Haven, CT USA. [Gelernter, J.] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT USA. [Kranzler, H. R.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. [Kranzler, H. R.] Philadelphia VA Med Ctr, VISN MIRECC 4, Philadelphia, PA USA. [Farrer, L. A.] Boston Univ, Sch Med, Dept Med Biomed Genet, Boston, MA 02118 USA. [Farrer, L. A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Farrer, L. A.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. [Farrer, L. A.] Boston Univ, Sch Med, Dept Genet & Genom, Boston, MA 02118 USA. [Farrer, L. A.] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA. [Farrer, L. A.] Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02118 USA. [Farrer, L. A.] Boston Univ, Sch Publ Hlth, Dept Med Biomed Genet, Boston, MA USA. [Farrer, L. A.] Boston Univ, Sch Publ Hlth, Dept Neurol, Boston, MA USA. [Farrer, L. A.] Boston Univ, Sch Publ Hlth, Dept Ophthalmol, Boston, MA USA. [Farrer, L. A.] Boston Univ, Sch Publ Hlth, Dept Genet & Genom, Boston, MA USA. [Farrer, L. A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Farrer, L. A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Wang, Y. J.] Capital Med Univ, Beijing Tiantan Hosp, Dept Neurol, Beijing, Peoples R China. RP Gu, WK (reprint author), Univ Tennessee, Ctr Hlth Sci, Campbell Clin, Dept Orthopaed Surg & BioMed Engn, Memphis, TN 38163 USA. EM wgu@uthsc.edu RI Li, Dawei/A-3466-2011; OI Farrer, Lindsay/0000-0001-5533-4225 FU National Institutes of Health, United States [AA016342, DA12849, DA12690, AA017535, AA12870, AA11330]; National Institutes of Health [N01-HG-65403]; Alkermes; Lilly; Lundbeck; Pfizer; Roche; Eli Lilly; Janssen; Schering Plough; GlaxoSmithKline; Abbott; Johnson Johnson FX Research supported by the National Institutes of Health, United States (research grants #AA016342, #DA12849, #DA12690, #AA017535, #AA12870, and #AA11330). Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University (contract #N01-HG-65403). Authors thank Dr. Robert Williams for his great assistance on the analysis of data in GeneNetwork and kindly reviewing of the manuscript.; Dr. Kranzler has been a paid consultant for Alkermes, Lilly, Lundbeck, Pfizer, and Roche. He also reports associations with Eli Lilly, Janssen, Schering Plough, Lundbeck, Alkermes, GlaxoSmithKline, Abbott, and Johnson & Johnson, as these companies provide support to the ACNP Alcohol Clinical Trials Initiative (ACTIVE) and Dr. Kranzler has received honoraria from ACTIVE. The other authors report no financial interests or potential conflicts of interest. NR 23 TC 3 Z9 2 U1 0 U2 1 PU FUNPEC-EDITORA PI RIBEIRAO PRETO PA RUA FLORIANO PEIXOTO 2444, ALTO DA BOA VISTA, RIBEIRAO PRETO, SP 00000, BRAZIL SN 1676-5680 J9 GENET MOL RES JI Genet. Mol. Res. PY 2013 VL 12 IS 4 BP 5992 EP 6005 DI 10.4238/2013.November.26.9 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA AB2FG UT WOS:000331608000188 PM 24338393 ER PT J AU Malins, AJ Milne, CP AF Malins, Ashley J. Milne, Christopher-Paul BE Mulberg, AE Murphy, D Dunne, J Mathis, LL TI Population Dynamics, Demographics and Disease Burden of Infants and Children across the World SO PEDIATRIC DRUG DEVELOPMENT: CONCEPTS AND APPLICATIONS, 2ND EDITION LA English DT Article; Book Chapter ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; SICKLE-CELL-DISEASE; MENTAL-HEALTH; GLOBAL BURDEN; UNITED-STATES; CHILDHOOD OBESITY; US ADOLESCENTS; PREVALENCE; ASTHMA; TRENDS C1 [Malins, Ashley J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Milne, Christopher-Paul] Tufts Univ, Sch Med, Ctr Study Drug, Boston, MA 02111 USA. [Milne, Christopher-Paul] Univ Edinburgh, Edinburgh, Midlothian, Scotland. RP Malins, AJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 153 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-31206-3 PY 2013 BP 16 EP 36 D2 10.1002/9781118312087 PG 21 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BJR82 UT WOS:000329855800004 ER PT J AU Milne, CP Malins, AJ AF Milne, Christopher-Paul Malins, Ashley J. BE Mulberg, AE Murphy, D Dunne, J Mathis, LL TI Pharmaceutical Economics and Market Access for Pediatric Medications SO PEDIATRIC DRUG DEVELOPMENT: CONCEPTS AND APPLICATIONS, 2ND EDITION LA English DT Article; Book Chapter ID CHILD HEALTH; US CHILDREN; ADOLESCENTS; PAIN; MANAGEMENT; MEDICINE; THERAPY; TRENDS; WORLD; DRUGS C1 [Milne, Christopher-Paul] Tufts Univ, Sch Med, Ctr Study Drug Dev, Boston, MA 02111 USA. [Milne, Christopher-Paul] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Malins, Ashley J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Milne, CP (reprint author), Tufts Univ, Sch Med, Ctr Study Drug Dev, Boston, MA 02111 USA. NR 103 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-31206-3 PY 2013 BP 37 EP 56 D2 10.1002/9781118312087 PG 20 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BJR82 UT WOS:000329855800005 ER PT J AU Liao, W Jordaan, G Srivastava, MK Dubinett, S Sharma, S Sharma, S AF Liao, Wei Jordaan, Gwen Srivastava, Minu K. Dubinett, Steven Sharma, Sherven Sharma, Sanjai TI Effect of epigenetic histone modifications on E-cadherin splicing and expression in lung cancer SO AMERICAN JOURNAL OF CANCER RESEARCH LA English DT Article DE E-cadherin; splicing; histone modifications; HDAC; HDAC inhibitor; Zeb1; EMT ID EPITHELIAL-MESENCHYMAL TRANSITION; MESSENGER-RNA DECAY; C-TERMINAL DOMAIN; TUMOR PROGRESSION; CHROMATIN MODIFICATIONS; CELL-LINES; GENE; METHYLATION; DISEASE; GROWTH AB We have identified an alternatively spliced, non-functional aberrant E-cadherin transcript that lacks exon 11 and is over expressed in malignant cells as compared to the normal non-malignant cells. This increase in the aberrant transcript is a mechanism of loss of E-cadherin gene expression as it is rapidly degraded by the nonsense mediated decay pathway. To study the mechanism of this gene missplicing we analyzed the role of histone epigenetic modifications in lung cancer cell lines. The treatment of low E-cadherin lung cancer cell lines with histone deacetylase inhibitor (HDACi, MS-275) resulted in the preferential expression of the correctly spliced transcripts in the low E-cadherin expressing cell lines only. Chromatin immunoprecipitation (ChIP) assays revealed that the histone hypoacetylation levels correlate with aberrant exon 11 splicing as there is more aberrant splicing in cell lines with E-cadherin promoter hypoacetylation. Inactivation of histone deacetylases (HDAC) 1, 2 and 3 resulted in an increase in E-cadherin expression and an increase in the ratio of the correctly spliced E-cadherin transcript. As transcription of the gene is closely linked to splicing, we considered the possibility that change in E-cadherin transcription correlates with splicing. The Zeb1 epithelial-mesenchymal transformation (EMT) inducer silences E-cadherin expression and could also alter the splicing of this exon. Inhibition of the E-cadherin promoter transcription with Zeb1 expression increases aberrant splicing and the reverse is observed when Zeb1 is knocked down. The role of HDAC inhibitors was also studied in vivo in a immunodeficient mouse xenograft model. Exposure of mice to HDACi resulted in growth inhibition, increase in E-cadherin expression, alteration of aberrant splicing and the reversal of EMT in mouse tumors. The findings support the modulation of E-cadherin exon 11 inclusion or exclusion by histone epigenetic modifications as they change the overall chromatin structure. The results provide an interesting link between epigenetic alterations in cancer cells and gene splicing in addition to their effect on gene silencing. C1 [Liao, Wei; Jordaan, Gwen; Srivastava, Minu K.; Dubinett, Steven; Sharma, Sherven; Sharma, Sanjai] UCLA West Los Angeles Vet Med Ctr, Div Hematol Oncol, Los Angeles, CA 90073 USA. [Srivastava, Minu K.; Dubinett, Steven; Sharma, Sherven] Vet Affairs Greater Los Angeles Healthcare Syst, Mol Med Lab, Los Angeles, CA USA. [Dubinett, Steven; Sharma, Sherven] Univ Calif Los Angeles, Div Pulm & Crit Care Med, Los Angeles, CA USA. RP Sharma, S (reprint author), UCLA West Los Angeles Vet Med Ctr, 11301 Wilshire Blvd,Bldg 304,Rm E1-115, Los Angeles, CA 90073 USA. EM sasharma@mednet.ucla.edu FU Flight Attendants Medical Research Institute (FAMRI); ASCO Foundation; VA Merit Research award; NIH [RO1 CA95686, RO1 CA126944, P50 CA90388]; UCLA Lung Cancer Program; VA Medical Research Funds; Tobacco Related Disease Program Award Program of University of California FX SS is a recipient of a grant from Flight Attendants Medical Research Institute (FAMRI), ASCO Foundation Young Investigator Award and a VA Merit Research award. Steven Dubinett and Sherven Sharma are supported by NIH Grants (RO1 CA95686, RO1 CA126944 and P50 CA90388), UCLA Lung Cancer Program, VA Medical Research Funds and Tobacco Related Disease Program Award Program of University of California. NR 54 TC 5 Z9 6 U1 0 U2 2 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 2156-6976 J9 AM J CANCER RES JI Am. J. Cancer Res. PY 2013 VL 3 IS 4 BP 374 EP 389 PG 16 WC Oncology SC Oncology GA AA4MJ UT WOS:000331069400004 PM 23977447 ER PT J AU Gollapudi, K Galet, C Grogan, T Zhang, H Said, JW Huang, J Elashoff, D Freedland, SJ Rettig, M Aronson, WJ AF Gollapudi, Kiran Galet, Colette Grogan, Tristan Zhang, Hong Said, Jonathan W. Huang, Jiaoti Elashoff, David Freedland, Stephen J. Rettig, Matthew Aronson, William J. TI Association between tumor-associated macrophage infiltration, high grade prostate cancer, and biochemical recurrence after radical prostatectomy SO AMERICAN JOURNAL OF CANCER RESEARCH LA English DT Article DE Biochemical recurrence; cancer development; prostate; tumor associated macrophages; tissue microarray ID BREAST-CANCER; EXPRESSION; INFLAMMATION; CELLS; ANGIOGENESIS; PROGRESSION; METASTASIS; PROGNOSIS; CARCINOMA; DENSITY AB Background: Tumor-associated macrophages (TAMs) are a key component of the inflammatory microenvironment. Their role in prostate cancer development and progression remains unclear. We examined whether the amount of TAMs in prostate cancer is: 1) higher than prostatic intraepithelial neoplasia (PIN) and benign tissue 2) associated with poorly differentiated disease, and 3) predictive of biochemical recurrence among surgically treated men. Methods: A tissue microarray (TMA) of prostatectomy specimens from 332 patients was stained for CD68, a TAM marker. A separate TMA was used for validation. Associations between mean TAMs in cancer cores and PSA recurrence were determined by Cox proportional hazards models after adjusting for age, preoperative PSA, race, body mass index, pathologic Gleason sum, seminal vesicle invasion, extracapsular extension, and margin status. Results: Mean TAM number was higher in cancer versus PIN and benign tissue (p<0.0001). Mean TAM number was higher in Gleason grade 4 cores vs. Gleason grade 3 cores (p=0.003). On multivariable analysis, no association was observed between mean TAM number per cancer core and biochemical recurrence in either cohort. Conclusion: Mean TAM number was higher in cancer cores vs. PIN and benign tissue, and higher in high grade prostate cancer supporting the potential role of TAMs in prostate cancer development. However, TAMs were not associated with biochemical recurrence after radical prostatectomy suggesting TAM counts do not provide independent prognostic value among surgically treated men. Further studies are required to elucidate the functional significance of TAMs in the prostate cancer microenvironment. C1 [Gollapudi, Kiran; Galet, Colette; Aronson, William J.] Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Grogan, Tristan; Elashoff, David] Univ Calif Los Angeles, Sch Med, Dept Med Stat Core, Los Angeles, CA 90095 USA. [Zhang, Hong; Said, Jonathan W.; Huang, Jiaoti] Univ Calif Los Angeles, Sch Med, Dept Pathol, Los Angeles, CA 90095 USA. [Freedland, Stephen J.] Duke Univ, Med Ctr, Durham Vet Affairs Med Ctr, Dept Surg, Durham, NC USA. [Freedland, Stephen J.] Duke Univ, Med Ctr, Div Urol Surg, Durham, NC USA. [Freedland, Stephen J.] Duke Univ, Med Ctr, Duke Prostate Ctr, Dept Surg, Durham, NC USA. [Freedland, Stephen J.] Duke Univ, Med Ctr, Duke Prostate Ctr, Dept Pathol, Durham, NC USA. [Rettig, Matthew] VA Greater Angeles Healthcare Syst, Dept Med, Div Hematol Oncol, Los Angeles, CA USA. [Aronson, William J.] VA Greater Angeles Healthcare Syst, Dept Surg, Urol Sect, Los Angeles, CA USA. RP Aronson, WJ (reprint author), Univ Calif Los Angeles, Sch Med, Dept Urol, Box 951738, Los Angeles, CA 90095 USA. EM kgollapudi@mednet.ucla.edu; waron-son@ucla.edu FU National Cancer Institute (NCI) [P50CA92131, 1K24CA160653-01]; Department of Veterans Affairs; Department of Defense [PC030686]; CTSI NIH [UL1TR000124]; UCLA Cancer Center [P30CA16042] FX We thank Dr Gholamhossein Pezeshkpour for his assistance in creating the WLA tissue microarray. We also thank Leah Gerber for her assistance in retrieving all necessary information from the WLA and Durham databases. This study was supported by National Cancer Institute (NCI) Grant Number P50CA92131 (WJA) and Grant Number 1K24CA160653-01 (SJF), The Department of Veterans Affairs (WJA), the Department of Defense Grant Number PC030686 (MR) and the CTSI NIH Grant Number UL1TR000124 (TG and DE) and UCLA Cancer Center (P30CA16042) (TG and DE). NR 25 TC 18 Z9 19 U1 0 U2 4 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 2156-6976 J9 AM J CANCER RES JI Am. J. Cancer Res. PY 2013 VL 3 IS 5 BP 523 EP 529 PG 7 WC Oncology SC Oncology GA AA4MK UT WOS:000331069500009 PM 24224130 ER PT J AU Katchar, K Drouin, EE Steere, AC AF Katchar, Kia Drouin, Elise E. Steere, Allen C. TI Natural killer cells and natural killer T cells in Lyme arthritis SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID ANTIBIOTIC-REFRACTORY ARTHRITIS; BORRELIA-BURGDORFERI; ERYTHEMA MIGRANS; NK CELLS; ADAPTIVE IMMUNITY; PERIPHERAL-BLOOD; DISEASE; ACTIVATION; ANTIGENS; THERAPY AB Introduction: Natural killer (NK) and natural killer T (NKT) cells provide a first line of defense against infection. However, these cells have not yet been examined in patients with Lyme arthritis, a late disease manifestation. Lyme arthritis usually resolves with antibiotic treatment. However, some patients have persistent arthritis after spirochetal killing, which may result from excessive inflammation, immune dysregulation and infection-induced autoimmunity. Methods: We determined the frequencies and phenotypes of NK cells and invariant NKT (iNKT) cells in paired peripheral blood (PB) and synovial fluid (SF) samples from eight patients with antibiotic-responsive arthritis and fifteen patients with antibiotic-refractory arthritis using flow cytometry and cytokine analyses. Results: In antibiotic-responsive patients, who were seen during active infection, high frequencies of CD56bright NK cells were found in SF, the inflammatory site, compared with PB (P <0.001); at both sites, a high percentage of cells expressed the activation receptor NKG2D and the chaperone CD94, a low percentage expressed inhibitory killer immunoglobulin-like receptors (KIR), and a high percentage produced IFN-gamma. In antibiotic-refractory patients, who were usually evaluated near the conclusion of antibiotics when few if any live spirochetes remained, the phenotype of CD56bright cells in SF was similar to that in patients with antibiotic-responsive arthritis, but the frequency of these cells was significantly less (P = 0.05), and the frequencies of CD56dim NK cells tended to be higher. However, unlike typical NKdim cells, these cells produced large amounts of IFN-gamma, suggesting that they were not serving a cytotoxic function. Lastly, iNKT cell frequencies in the SF of antibiotic-responsive patients were significantly greater compared with that of antibiotic-refractory patients where these cells were often absent (P = 0.003). Conclusions: In patients with antibiotic-responsive arthritis, the high percentage of activated, IFN-gamma-producing CD56bright NK cells in SF and the presence of iNKT cells suggest that these cells still have a role in spirochetal killing late in the illness. In patients with antibiotic-refractory arthritis, the frequencies of IFN-gamma-producing CD56bright and CD56dim NK cells remained high in SF, even after spirochetal killing, suggesting that these cells contribute to excessive inflammation and immune dysregulation in joints, and iNKT cells, which may have immunomodulatory effects, were often absent. C1 [Katchar, Kia; Drouin, Elise E.; Steere, Allen C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol, Boston, MA 02114 USA. RP Steere, AC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol, CNY 149-8301,55 Fruit St, Boston, MA 02114 USA. EM asteere@partners.org FU NIH [AI-101175, AR-20358]; Lillian B. Davey Foundation for the study of Lyme disease; English, Bonter, Mitchell Foundation; Lyme/Arthritis Research Fund; Eshe Fund FX We thank Gail McHugh and Klemen Strle for help with the collection of patient samples. This research was supported by NIH grant AI-101175 and AR-20358, the English, Bonter, Mitchell Foundation, the Lyme/Arthritis Research Fund at Massachusetts General Hospital, and the Eshe Fund. Dr. Katchar received a scholarship from the Lillian B. Davey Foundation for the study of Lyme disease. NR 48 TC 7 Z9 9 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2013 VL 15 IS 6 AR R183 DI 10.1186/ar4373 PG 11 WC Rheumatology SC Rheumatology GA 302TW UT WOS:000330628800009 PM 24286535 ER PT J AU Singh, JA AF Singh, Jasvinder A. TI Veterans Affairs databases are accurate for gout-related health care utilization: a validation study SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID QUALITY-OF-LIFE; POPULATION; DIAGNOSES; COSTS; COMORBIDITIES; ARTHRITIS; PATTERNS; COHORT; FLARES AB Introduction: The aim of this study was to assess the accuracy of Veterans Affairs (VA) databases for gout-related health care utilization. Methods: This retrospective study utilized VA administrative and clinical databases. A random sample of gout patients with visits (outpatient, inpatient or emergent/urgent care) with or without the diagnosis of gout (International Classification of Diseases, ninth revision, common modification ICD-9-CM code of 274.x or 274.xx) at the Birmingham VA hospital was selected. A blinded abstractor performed a review of VA electronic health records for the documentation of gout or gout-related terms (gouty arthritis, tophaceous gout, tophus/tophi, acute gout, chronic gout, podagra, urate stones, urate or uric acid crystals and so on) in the chief complaint, history of present illness or assessment and plan for the visit; this constituted the gold standard for gout-related utilization. The accuracy of database-derived gout-related claims was assessed by calculating sensitivity, specificity, and positive and negative predictive values (PPV and NPV). Results: Of 108 potential visits, 85 outpatient, inpatient or urgent care/emergency room visits to a health care provider (85 patients: 84 men and 1 woman with a mean age of 63 years) and retrievable data from medical records constituted the analyzed dataset. Administrative claims for gout-related utilization with ICD-9 code for gout were accurate with a PPV of 86%, specificity of 95%, sensitivity of 86% and NPV of 95%. Conclusions: VA databases are accurate for gout-related visits. These findings support their use for studies of health services and outcome studies. It remains to be seen if these findings are generalizable to other settings and databases. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35233 USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit C SMART, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, 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 Takeda Pharmaceuticals USA, Inc.; National Institutes of Arthritis, Musculoskeletal and Skin Diseases (NIAMS); National Institutes of Aging (NIA); National Cancer Institute (NCI); Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs) FX I thank Michael Conner, BS from Birmingham VA Medical Center, for creating a random sample of gout and non-gout visits. Takeda Pharmaceuticals USA, Inc. funded this investigator-initiated study, but had no contribution to the study design, analytic plan, data collection, analyses or the decision to submit the study. The study author (Dr. Singh) developed study protocol, performed data collection and data analyses, prepared the manuscript and made the decision to submit the manuscript. An internal review committee at Takeda Pharmaceuticals reviewed a draft of the manuscript and provided comments to the author. The decision to or not to incorporate these comments was made by the author (Dr. Singh). Dr. Singh is also supported by research grants from the National Institutes of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Aging (NIA), National Cancer Institute (NCI) and the Agency for Health Quality and Research Center for Education and Research on Therapeutics (CERTs), and the resources and use of facilities at the Birmingham VA Medical Center. NR 18 TC 9 Z9 9 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2013 VL 15 IS 6 AR R224 DI 10.1186/ar4425 PG 5 WC Rheumatology SC Rheumatology GA 302TW UT WOS:000330628800050 PM 24377421 ER PT J AU Arnardottir, ES Janson, C Bjornsdottir, E Benediktsdottir, B Juliusson, S Kuna, ST Pack, AI Gislason, T AF Arnardottir, Erna Sif Janson, Christer Bjornsdottir, Erla Benediktsdottir, Bryndis Juliusson, Sigurdur Kuna, Samuel T. Pack, Allan I. Gislason, Thorarinn TI Nocturnal sweating - a common symptom of obstructive sleep apnoea: the Icelandic sleep apnoea cohort SO BMJ OPEN LA English DT Article ID NIGHT SWEATS; GASTROESOPHAGEAL-REFLUX; CARE PATIENTS; LUNG-FUNCTION; PREVALENCE; OKPRN; EPIDEMIOLOGY; ASSOCIATIONS; RELIABILITY; PRESSURE AB Objectives: To estimate the prevalence and characteristics of frequent nocturnal sweating in obstructive sleep apnoea (OSA) patients compared with the general population and evaluate the possible changes with positive airway pressure (PAP) treatment. Nocturnal sweating can be very bothersome to the patient and bed partner. Design: Case-control and longitudinal cohort study. Setting: Landspitali-The National University Hospital, Iceland. Participants: The Icelandic Sleep Apnea Cohort consisted of 822 untreated patients with OSA, referred for treatment with PAP. Of these, 700 patients were also assessed at a 2-year follow-up. The control group consisted of 703 randomly selected subjects from the general population. Intervention: PAP therapy in the OSA cohort. Main outcome measures: Subjective reporting of nocturnal sweating on a frequency scale of 1-5: (1) never or very seldom, (2) less than once a week, (3) once to twice a week, (4) 3-5 times a week and (5) every night or almost every night. Full PAP treatment was defined objectively as the use for = 4 h/day and = 5 days/week. Results: Frequent nocturnal sweating (= 3x a week) was reported by 30.6% of male and 33.3% of female OSA patients compared with 9.3% of men and 12.4% of women in the general population (p<0.001). This difference remained significant after adjustment for demographic factors. Nocturnal sweating was related to younger age, cardiovascular disease, hypertension, sleepiness and insomnia symptoms. The prevalence of frequent nocturnal sweating decreased with full PAP treatment (from 33.2% to 11.5%, p<0.003 compared with the change in non-users). Conclusions: The prevalence of frequent nocturnal sweating was threefold higher in untreated OSA patients than in the general population and decreased to general population levels with successful PAP therapy. Practitioners should consider the possibility of OSA in their patients who complain of nocturnal sweating. C1 [Arnardottir, Erna Sif; Bjornsdottir, Erla; Benediktsdottir, Bryndis; Gislason, Thorarinn] Natl Univ Hosp Iceland, Landspitali, Dept Resp Med & Sleep, Reykjavik, Iceland. [Arnardottir, Erna Sif; Bjornsdottir, Erla; Benediktsdottir, Bryndis; Gislason, Thorarinn] Univ Iceland, Sch Hlth Sci, Fac Med, Reykjavik, Iceland. [Janson, Christer] Uppsala Univ, Dept Med Sci Resp Med & Allergol, Uppsala, Sweden. [Juliusson, Sigurdur] Natl Univ Hosp Iceland, Landspitali, Dept Otolaryngol, Reykjavik, Iceland. [Kuna, Samuel T.] Univ Penn, Sch Med, Dept Med, Div Sleep Med,Ctr Sleep & Circadian Neurobiol, Philadelphia, PA 19104 USA. [Kuna, Samuel T.] Philadelphia Vet Affairs Med Ctr, Dept Med, Philadelphia, PA USA. RP Gislason, T (reprint author), Natl Univ Hosp Iceland, Landspitali, Dept Resp Med & Sleep, Reykjavik, Iceland. EM thorarig@landspitali.is FU NIH [HL72067, HL94307]; University of Iceland; Landspitali University Hospital Research Fund FX NIH grant HL72067 for "A Family Linkage Study of Obstructive Sleep Apnoea" and HL94307 for "Endophenotypes of Sleep Apnea and Role of Obesity", the Eimskip fund of the University of Iceland and the Landspitali University Hospital Research Fund. NR 36 TC 4 Z9 4 U1 0 U2 1 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 2013 VL 3 IS 5 AR e002795 DI 10.1136/bmjopen-2013-002795 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 301NF UT WOS:000330538300081 ER PT J AU Bajunirwe, F Twesigye, L Zhang, M Kerry, VB Bangsberg, DR AF Bajunirwe, Francis Twesigye, Leonidas Zhang, Michael Kerry, Vanessa B. Bangsberg, David R. TI Influence of the US President's Emergency Plan for AIDS Relief (PEPfAR) on career choices and emigration of health-profession graduates from a Ugandan medical school: a cross-sectional study SO BMJ OPEN LA English DT Article ID RETROSPECTIVE COHORT; RURAL PRACTICE; BRAIN-DRAIN; STUDENTS; INITIATIVES; PREFERENCES; DOCTORS; ZAMBIA AB Objective: The purpose of this study was to determine the current work distribution of health professionals from a public Ugandan medical school in a period of major donor funding for HIV programmes. We explore the hypothesis that programmes initiated under unprecedented health investments from the US President's Emergency Plan for AIDS Relief have possibly facilitated the drain of healthcare workers from the public-health system of countries like Uganda. Design: Cross-sectional study conducted between January and December 2010 to survey graduates, using in-person, phone or online surveys using email and social networks. Logistic regression analysis was applied to determine ORs for association between predictors and outcomes. Setting: Located rurally, Mbarara University of Science and Technology (MUST) is one of three government supported medical schools in Uganda. Participants: Graduates who completed a health-related degree at MUST. Main outcome measure: Location of health profession graduates (Uganda or abroad) and main field of current job (HIV-related non-governmental organisation (NGO) or others). Results: We interviewed 85.4% (n=796) of all MUST alumni since the university opened in 1989. 78% (n=618) were physicians and 12% (n=94) of graduates worked outside Uganda. Over 50% (n=383) of graduates worked for an HIV-related NGO whether in Uganda or abroad. Graduates receiving their degree after 2005, when large HIV programmes started, were less likely to leave the country, OR=0.24 (95% CI 0.1 to 0.59) but were more likely to work for an HIV-related NGO, OR=1.53 (95% CI 1.06 to 2.23). Conclusions: A majority of health professionals surveyed work for an HIV-related NGO. The increase in resources and investment in HIV-treatment capacity is temporally associated with retention of medical providers in Uganda. Donor funds should be channelled to develop and retain healthcare workers in disciplines other than HIV and broaden the healthcare workforce to other areas. C1 [Bajunirwe, Francis; Twesigye, Leonidas; Bangsberg, David R.] Mbarara Univ Sci & Technol, Dept Community Hlth, Mbarara, Uganda. [Zhang, Michael; Kerry, Vanessa B.; Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Kerry, Vanessa B.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Bangsberg, David R.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Bajunirwe, F (reprint author), Mbarara Univ Sci & Technol, Dept Community Hlth, Mbarara, Uganda. EM fbaj@yahoo.com FU Rockefeller Foundation [2009 THS 313] FX The study was funded by a Rockefeller Foundation grant to Mbarara University (Grant #2009 THS 313). NR 24 TC 8 Z9 8 U1 1 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 2013 VL 3 IS 5 AR e002875 DI 10.1136/bmjopen-2013-002875 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 301NF UT WOS:000330538300095 ER PT J AU Cannon, CM Levy, P Baumann, BM Borczuk, P Chandra, A Cline, DM Diercks, DB Hiestand, B Hsu, A Jois, P Kaminski, B Nowak, RM Schrock, JW Varon, J Peacock, WF AF Cannon, Chad M. Levy, Phillip Baumann, Brigitte M. Borczuk, Pierre Chandra, Abhinav Cline, David M. Diercks, Deborah B. Hiestand, Brian Hsu, Amy Jois, Preeti Kaminski, Brian Nowak, Richard M. Schrock, Jon W. Varon, Joseph Peacock, W. Frank TI Intravenous nicardipine and labetalol use in hypertensive patients with signs or symptoms suggestive of end-organ damage in the emergency department: a subgroup analysis of the CLUE trial SO BMJ OPEN LA English DT Article ID BLOOD-PRESSURE; UNITED-STATES; MANAGEMENT; STROKE; PREVALENCE; URGENCIES; OUTCOMES; CRISIS AB Objective: To compare the efficacy of Food and Drug Administration recommended dosing of nicardipine versus labetalol for the management of hypertensive patients with signs and/or symptoms (S/S) suggestive of end-organ damage (EOD). Design: Secondary analysis of the multicentre prospective, randomised CLUE trial. Setting: 13 academic emergency departments in the USA. Participants: Eligible patients had two systolic blood pressure (SBP) measures >= 180 mm Hg at least 10 min apart, no contraindications to nicardipine or labetalol and predefined S/S suggestive of EOD on arrival. Interventions: Medications were administered by continuous infusion (nicardipine) or repeat intravenous bolus (labetalol) for a study period of 30 min or until a specified target SBP +/- 20 mm Hg was achieved. Primary outcome measure: Percentage of participants achieving a predefined target SBP range (TR) defined as an SBP within +/- 20 mm Hg as established by the treating physician. Results: Of the 141 eligible patients, 49.6% received nicardipine, 51.7% were women and 81.6% were black. Mean age was 52.2 +/- 13.9 years. Median initial SBP did not differ in the nicardipine (210.5 (IQR 197-226) mm Hg) and labetalol (210 (200-226) mm Hg) groups (p=0.862). Nicardipine patients were more likely to have a history of diabetes (41.4% vs 25.7%, p=0.05) but there were no other historical, demographic or laboratory differences between groups. Within 30 min, nicardipine patients more often reached the target SBP range than those receiving labetalol (91.4% vs 76.1%, difference=15.3% (95% CI 3.5% to 27.3%); p=0.01). On multivariable modelling with adjustment for gender and clinical site, nicardipine patients were more likely to be in TR by 30 min than patients receiving labetalol (OR 3.65, 95% CI 1.31 to 10.18, C statistic=0.72). Conclusions: In the setting of hypertension with suspected EOD, patients treated with nicardipine are more likely to reach prespecified SBP targets within 30 min than patients receiving labetalol. C1 [Cannon, Chad M.] Univ Kansas Hosp, Dept Emergency Med, Kansas City, KS 66103 USA. [Levy, Phillip] Wayne State Univ, Dept Emergency Med, Detroit, MI USA. [Levy, Phillip] Wayne State Univ, Cardiovasc Res Inst, Detroit, MI USA. [Baumann, Brigitte M.] Cooper Univ Hosp, Div Clin Res, Camden, NJ USA. [Baumann, Brigitte M.] Cooper Univ Hosp, Dept Emergency Med, Camden, NJ USA. [Borczuk, Pierre] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Chandra, Abhinav] Duke Univ, Med Ctr, Div Emergency Med, Durham, NC USA. [Cline, David M.; Hiestand, Brian] Wake Forest Sch Med, Dept Emergency Med, Salem, NC USA. [Diercks, Deborah B.] Univ Calif, Davis Med Ctr, Dept Emergency Med, Sacramento, CA USA. [Hiestand, Brian] Ohio State Univ, Dept Emergency Med, Columbus, OH 43210 USA. [Hsu, Amy] Cleveland Clin, Cleveland, OH 44106 USA. [Jois, Preeti] Univ Florida, Coll Med, Dept Emergency Med, Gainesville, FL USA. [Kaminski, Brian] Toledo Hosp, Toledo, OH USA. [Nowak, Richard M.] Henry Ford Hosp, Dept Emergency Med, Detroit, MI 48202 USA. [Schrock, Jon W.] Case Western Reserve Univ, Sch Med, Dept Emergency Med, MetroHlth Med Ctr, Cleveland, OH USA. [Varon, Joseph] Univ Texas Hlth Sci Ctr Houston, Dept Med & Acute & Continuing Care, Houston, TX 77030 USA. [Varon, Joseph] Univ Texas Med Branch Galveston, Houston, TX USA. [Peacock, W. Frank] Baylor Coll Med, Dept Emergency Med, Houston, TX 77030 USA. RP Cannon, CM (reprint author), Univ Kansas Hosp, Dept Emergency Med, Kansas City, KS 66103 USA. EM ccannon@kumc.edu OI Varon, Joseph/0000-0002-7622-9974 FU EKR Therapeutics, Inc. FX This study was performed with a funding support from EKR Therapeutics, Inc. The authors retained access to data and were responsible for all decisions to publish this manuscript. NR 18 TC 2 Z9 2 U1 1 U2 5 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 2013 VL 3 IS 3 AR e002338 DI 10.1136/bmjopen-2012-002338 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 301VP UT WOS:000330560500046 ER PT J AU David, SM Salzillo, S Bowe, P Scuncio, S Malit, B Raker, C Gass, JS Granai, CO Dizon, DS AF David, Shannon MacLaughlan Salzillo, Sandra Bowe, Patrick Scuncio, Sandra Malit, Bridget Raker, Christina Gass, Jennifer S. Granai, C. O. Dizon, Don S. TI Randomised controlled trial comparing hypnotherapy versus gabapentin for the treatment of hot flashes in breast cancer survivors: a pilot study SO BMJ OPEN LA English DT Article ID QUALITY-OF-LIFE; DOUBLE-BLIND; ALTERNATIVE MEDICINE; REPLACEMENT THERAPY; MENOPAUSAL SYMPTOMS; YOUNGER WOMEN; MANAGEMENT; PLACEBO; VENLAFAXINE; TAMOXIFEN AB Objectives: To compare the efficacy of hypnotherapy versus gabapentin for the treatment of hot flashes in breast cancer survivors, and to evaluate the feasibility of conducting a clinical trial comparing a drug with a complementary or alternative method (CAM). Design: Prospective randomised trial. Setting: Breast health centre of a tertiary care centre. Participants: 15 women with a personal history of breast cancer or an increased risk of breast cancer who reported at least one daily hot flash. Interventions: Gabapentin 900 mg daily in three divided doses (control) compared with standardised hypnotherapy. Participation lasted 8 weeks. Outcome measures: The primary endpoints were the number of daily hot flashes and hot flash severity score (HFSS). The secondary endpoint was the Hot Flash Related Daily Interference Scale (HFRDIS). Results: 27 women were randomised and 15 (56%) were considered evaluable for the primary endpoint (n=8 gabapentin, n=7 hypnotherapy). The median number of daily hot flashes at enrolment was 4.5 in the gabapentin arm and 5 in the hypnotherapy arm. HFSS scores were 7.5 in the gabapentin arm and 10 in the hypnotherapy arm. After 8 weeks, the median number of daily hot flashes was reduced by 33.3% in the gabapentin arm and by 80% in the hypnotherapy arm. The median HFSS was reduced by 33.3% in the gabapentin arm and by 85% in the hypnotherapy arm. HFRDIS scores improved by 51.6% in the gabapentin group and by 55.2% in the hypnotherapy group. There were no statistically significant differences between groups. Conclusions: Hypnotherapy and gabapentin demonstrate efficacy in improving hot flashes. A definitive trial evaluating traditional interventions against CAM methods is feasible, but not without challenges. Further studies aimed at defining evidence-based recommendations for CAM are necessary. C1 [David, Shannon MacLaughlan] Stanford Univ, Stanford Womens Canc Ctr, Dept Obstet & Gynecol, Stanford, CA 94305 USA. [Salzillo, Sandra; Scuncio, Sandra; Raker, Christina; Gass, Jennifer S.; Granai, C. O.] Brown Univ, Program Womens Oncol, Women & Infants Hosp, Alpert Med Sch, Providence, RI 02912 USA. [Bowe, Patrick] Providence Hypnosis Ctr, Providence, RI USA. [Malit, Bridget] Cornell Univ, Weill Cornell Med Coll, Dept Pediat, New York, NY 10021 USA. [Dizon, Don S.] Harvard Univ, Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02115 USA. RP David, SM (reprint author), Stanford Univ, Stanford Womens Canc Ctr, Dept Obstet & Gynecol, Stanford, CA 94305 USA. EM smaclaug@stanford.edu NR 33 TC 7 Z9 7 U1 1 U2 5 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 2013 VL 3 IS 9 AR e003138 DI 10.1136/bmjopen-2013-003138 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 301ON UT WOS:000330541900018 ER PT J AU Meyer, MJ Stanislaus, AB Lee, J Waak, K Ryan, C Saxena, R Ball, S Schmidt, U Poon, T Piva, S Walz, M Talmor, DS Blobner, M Latronico, N Eikermann, M AF Meyer, Matthew J. Stanislaus, Anne B. Lee, Jarone Waak, Karen Ryan, Cheryl Saxena, Richa Ball, Stephanie Schmidt, Ulrich Poon, Trudy Piva, Simone Walz, Matthias Talmor, Daniel S. Blobner, Manfred Latronico, Nicola Eikermann, Matthias TI Surgical Intensive Care Unit Optimal Mobilisation Score (SOMS) trial: a protocol for an international, multicentre, randomised controlled trial focused on goal-directed early mobilisation of surgical ICU patients SO BMJ OPEN LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; CRITICALLY-ILL PATIENTS; LENGTH-OF-STAY; NEUROMUSCULAR WEAKNESS; PREDICTS MORTALITY; PHYSICAL MEDICINE; CLINICAL-TRIALS; MUSCLE WEAKNESS; BRAIN-INJURY; FAILURE AB Introduction: Immobilisation in the intensive care unit (ICU) leads to muscle weakness and is associated with increased costs and long-term functional disability. Previous studies showed early mobilisation of medical ICU patients improves clinical outcomes. The Surgical ICU Optimal Mobilisation Score (SOMS) trial aims to test whether a budget-neutral intervention to facilitate goal-directed early mobilisation in the surgical ICU improves participant mobilisation and associated clinical outcomes. Methods and analysis: The SOMS trial is an international, multicentre, randomised clinical study being conducted in the USA and Europe. We are targeting 200 patients. The primary outcome is average daily SOMS level and key secondary outcomes are ICU length of stay until discharge readiness and 'mini' modified Functional Independence Measure (mmFIM) at hospital discharge. Additional secondary outcomes include quality of life assessed at 3 months after hospital discharge and global muscle strength at ICU discharge. Exploratory outcomes will include: ventilator-free days, ICU and hospital length of stay and 3-month mortality. We will explore genetic influences on the effectiveness of early mobilisation and centre-specific effects of early mobilisation on outcomes. Ethics and dissemination: Following Institutional Review Board (IRB) approval in three institutions, we started study recruitment and plan to expand to additional centres in Germany and Italy. Safety monitoring will be the domain of the Data and Safety Monitoring Board (DSMB). The SOMS trial will also explore the feasibility of a transcontinental study on early mobilisation in the surgical ICU. Results: The results of this study, along with those of ancillary studies, will be made available in the form of manuscripts and presentations at national and international meetings. C1 [Meyer, Matthew J.; Stanislaus, Anne B.; Saxena, Richa; Schmidt, Ulrich; Poon, Trudy; Eikermann, Matthias] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Meyer, Matthew J.; Stanislaus, Anne B.; Lee, Jarone; Saxena, Richa; Schmidt, Ulrich; Poon, Trudy; Eikermann, Matthias] Harvard Univ, Sch Med, Boston, MA USA. [Lee, Jarone] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Waak, Karen] Massachusetts Gen Hosp, Dept Phys & Occupat Therapy, Boston, MA 02114 USA. [Ryan, Cheryl; Ball, Stephanie] Massachusetts Gen Hosp, Dept Clin Nursing Serv, Boston, MA 02114 USA. [Piva, Simone; Latronico, Nicola] Univ Brescia, Spedali Civili, Dept Anesthesia Intens Care & Perioperat Med, Brescia, Italy. [Walz, Matthias] UMass Mem Med Ctr, Worcester, MA USA. [Walz, Matthias] UMass Med Sch, Worcester, MA USA. [Talmor, Daniel S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02215 USA. [Blobner, Manfred] Tech Univ Munich, Klinikum Rechts Isar, Klin Anaesthesiol, D-80290 Munich, Germany. [Eikermann, Matthias] Univ Duisburg Essen, Essen, Germany. RP Eikermann, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM meikermann@partners.org RI Piva, Simone/E-1902-2014; Latronico, Nicola/F-1557-2010; OI Piva, Simone/0000-0002-5483-8007; Latronico, Nicola/0000-0002-2521-5871; Lee, Jarone/0000-0002-4532-8523 NR 54 TC 7 Z9 8 U1 2 U2 11 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 2013 VL 3 IS 8 AR e003262 DI 10.1136/bmjopen-2013-003262 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 301VX UT WOS:000330561300051 PM 23959756 ER PT J AU Sukumar, S Roghmann, F Trinh, VQ Sammon, JD Gervais, MK Tan, HJ Ravi, P Kim, SP Hu, JC Karakiewicz, PI Noldus, J Sun, M Menon, M Trinh, QD AF Sukumar, Shyam Roghmann, Florian Trinh, Vincent Q. Sammon, Jesse D. Gervais, Mai-Kim Tan, Hung-Jui Ravi, Praful Kim, Simon P. Hu, Jim C. Karakiewicz, Pierre I. Noldus, Joachim Sun, Maxine Menon, Mani Quoc-Dien Trinh TI National trends in hospital-acquired preventable adverse events after major cancer surgery in the USA SO BMJ OPEN LA English DT Article ID HIGH-VOLUME HOSPITALS; MORTALITY; FAILURE; RESCUE; SAFETY; CARE; DISPARITIES; MORBIDITY; ADULTS AB Objectives: While multiple studies have demonstrated variations in the quality of cancer care in the USA, payers are increasingly assessing structure-level and process-level measures to promote quality improvement. Hospital-acquired adverse events are one such measure and we examine their national trends after major cancer surgery. Design: Retrospective, cross-sectional analysis of a weighted-national estimate from the Nationwide Inpatient Sample (NIS) undergoing major oncological procedures (colectomy, cystectomy, oesophagectomy, gastrectomy, hysterectomy, lung resection, pancreatectomy and prostatectomy). The Agency for Healthcare Research and Quality Patient Safety Indicators (PSIs) were utilised to identify trends in hospital-acquired adverse events. Setting: Secondary and tertiary care, US hospitals in NIS Participants: A weighted-national estimate of 2 508 917 patients (>18 years, 1999-2009) from NIS. Primary outcome measures: Hospital-acquired adverse events. Results: 324 852 patients experienced >= 1-PSI event (12.9%). Patients with >= 1-PSI experienced higher rates of in-hospital mortality (OR 19.38, 95% CI 18.44 to 20.37), prolonged length of stay (OR 4.43, 95% CI 4.31 to 4.54) and excessive hospital-charges (OR 5.21, 95% CI 5.10 to 5.32). Patients treated at lower volume hospitals experienced both higher PSI events and failure-to- rescue rates. While a steady increase in the frequency of PSI events after major cancer surgery has occurred over the last 10 years (estimated annual % change (EAPC): 3.5%, p<0.001), a concomitant decrease in failure-to-rescue rates (EAPC -3.01%) and overall mortality (EAPC -2.30%) was noted (all p<0.001). Conclusions: Over the past decade, there has been a substantial increase in the national frequency of potentially avoidable adverse events after major cancer surgery, with a detrimental effect on numerous outcome-level measures. However, there was a concomitant reduction in failure-to-rescue rates and overall mortality rates. Policy changes to improve the increasing burden of specific adverse events, such as postoperative sepsis, pressure ulcers and respiratory failure, are required. C1 [Sukumar, Shyam; Sammon, Jesse D.; Ravi, Praful; Menon, Mani] Henry Ford Hlth Syst, Ctr Outcomes Res & Analyt, Detroit, MI USA. [Roghmann, Florian; Trinh, Vincent Q.; Karakiewicz, Pierre I.; Sun, Maxine; Quoc-Dien Trinh] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada. [Roghmann, Florian; Noldus, Joachim] Ruhr Univ Bochum, Marienhosp, Dept Urol, Herne, Germany. [Gervais, Mai-Kim] Univ Montreal, Ctr Hlth, Div Gen Surg, Montreal, PQ, Canada. [Tan, Hung-Jui] Univ Michigan, Dow Div Hlth Serv Res, Ann Arbor, MI 48109 USA. [Kim, Simon P.] Mayo Clin, Dept Urol, Rochester, MN USA. [Hu, Jim C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Quoc-Dien Trinh] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Surg,Div Urol, Boston, MA 02115 USA. RP Roghmann, F (reprint author), Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada. EM f.roghmann@gmail.com NR 27 TC 10 Z9 10 U1 1 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 2013 VL 3 IS 6 AR e002843 DI 10.1136/bmjopen-2013-002843 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 301WA UT WOS:000330561600041 ER PT J AU Battelli, C Campo, M Buss, MK Awtrey, CS Konstantinopoulos, PA AF Battelli, Chiara Campo, Meghan Buss, Mary K. Awtrey, Christopher S. Konstantinopoulos, Panagiotis A. TI Safety and Outcome of Patients Treated with a Modified Outpatient Intraperitoneal Regimen for Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancer SO CHEMOTHERAPY LA English DT Article DE Cisplatin; Intraperitoneal chemotherapy; Intravenous chemotherapy; Ovarian cancer; Overall survival; Paclitaxel; Progression-free survival ID GYNECOLOGIC-ONCOLOGY-GROUP; STAGE-III OVARIAN; INTRAVENOUS PACLITAXEL; CISPLATIN; CHEMOTHERAPY; TRIAL; CARCINOMA; CYCLOPHOSPHAMIDE; CARBOPLATIN; RECURRENCE AB Background: Despite the survival benefit of intraperitoneal (IP) chemotherapy observed in GOG172, significant toxicity and poor treatment completion rates have prevented the widespread acceptance of this regimen. Here, we report our experience with a modified outpatient GOG172 regimen. Methods: Eligible patients had stage III, optimally debulked epithelial ovarian, fallopian tube or primary peritoneal cancer that underwent IP port placement for administration of a modified GOG172 regimen consisting of: (i) intravenous paclitaxel 135 mg/m(2) on day 1 over 3 h; (ii) intraperitoneal cisplatin 75 mg/m(2) on day 2, and (iii) intraperitoneal paclitaxel 60 mg/m(2) on day 8. Day 8 IP paclitaxel was omitted until tolerance of the first cycle of IP cisplatin had been established. Results: Four or more cycles of IP chemotherapy were completed by 72.5% (29) of 40 eligible patients; 20% of patients exhibited catheter-related complications requiring port removal and discontinuation of IP chemotherapy. Grade 3-4 hematologic, metabolic and gastrointestinal toxicities occurred in 36, 8 and 21% of the patients, respectively. With a median follow-up of 47.7 months, progression-free and overall survival was comparable to GOG172. Conclusions: This modified outpatient GOG172 regimen is associated with less toxicity and improved completion rates compared to the original GOG172 regimen. (C) 2014 S. Karger AG, Basel C1 [Battelli, Chiara] Maine Ctr Canc Med, Scarborough, ME USA. [Battelli, Chiara; Campo, Meghan; Buss, Mary K.; Konstantinopoulos, Panagiotis A.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Hematol Oncol, Boston, MA 02215 USA. [Awtrey, Christopher S.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol,Div Gynecol Oncol, Boston, MA 02215 USA. [Konstantinopoulos, Panagiotis A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med,Div Med Gynecol Oncol, Boston, MA 02215 USA. RP Konstantinopoulos, PA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med,Div Med Gynecol Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM panagiotis_konstantinopoulos@dfci.harvard.edu NR 25 TC 3 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0009-3157 EI 1421-9794 J9 CHEMOTHERAPY JI Chemotherapy PY 2013 VL 59 IS 4 BP 251 EP 259 DI 10.1159/000356758 PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA AA8YO UT WOS:000331381100003 PM 24457572 ER PT J AU Pfefferle, AD Herschkowitz, JI Usary, J Harrell, JC Spike, BT Adams, JR Torres-Arzayus, MI Brown, M Egan, SE Wahl, GM Rosen, JM Perou, CM AF Pfefferle, Adam D. Herschkowitz, Jason I. Usary, Jerry Harrell, Joshua Chuck Spike, Benjamin T. Adams, Jessica R. Torres-Arzayus, Maria I. Brown, Myles Egan, Sean E. Wahl, Geoffrey M. Rosen, Jeffrey M. Perou, Charles M. TI Transcriptomic classification of genetically engineered mouse models of breast cancer identifies human subtype counterparts SO GENOME BIOLOGY LA English DT Article ID TRANSGENIC MICE; GROWTH-FACTOR; BASAL-LIKE; MAMMARY-TUMORS; MOLECULAR PORTRAITS; IONIZING-RADIATION; METASTATIC-DISEASE; ATTRITION RATES; LUMINAL-B; EXPRESSION AB Background: Human breast cancer is a heterogeneous disease consisting of multiple molecular subtypes. Genetically engineered mouse models are a useful resource for studying mammary cancers in vivo under genetically controlled and immune competent conditions. Identifying murine models with conserved human tumor features will facilitate etiology determinations, highlight the effects of mutations on pathway activation, and should improve preclinical drug testing. Results: Transcriptomic profiles of 27 murine models of mammary carcinoma and normal mammary tissue were determined using gene expression microarrays. Hierarchical clustering analysis identified 17 distinct murine subtypes. Cross-species analyses using three independent human breast cancer datasets identified eight murine classes that resemble specific human breast cancer subtypes. Multiple models were associated with human basal-like tumors including TgC3(1)-Tag, TgWAP-Myc and Trp53(-/-). Interestingly, the TgWAPCre-Etv6 model mimicked the HER2-enriched subtype, a group of human tumors without a murine counterpart in previous comparative studies. Gene signature analysis identified hundreds of commonly expressed pathway signatures between linked mouse and human subtypes, highlighting potentially common genetic drivers of tumorigenesis. Conclusions: This study of murine models of breast carcinoma encompasses the largest comprehensive genomic dataset to date to identify human-to-mouse disease subtype counterparts. Our approach illustrates the value of comparisons between species to identify murine models that faithfully mimic the human condition and indicates that multiple genetically engineered mouse models are needed to represent the diversity of human breast cancers. The reported trans-species associations should guide model selection during preclinical study design to ensure appropriate representatives of human disease subtypes are used. C1 [Pfefferle, Adam D.; Perou, Charles M.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. [Pfefferle, Adam D.; Usary, Jerry; Harrell, Joshua Chuck; Perou, Charles M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Herschkowitz, Jason I.] SUNY Albany, Dept Biomed Sci, Rensselaer, NY 12144 USA. [Usary, Jerry; Harrell, Joshua Chuck; Perou, Charles M.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Spike, Benjamin T.; Wahl, Geoffrey M.] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92130 USA. [Adams, Jessica R.; Egan, Sean E.] Peter Gilgan Ctr Res & Learning, Program Dev & Stem Cell Biol, Toronto, ON M5G 1X8, Canada. [Torres-Arzayus, Maria I.; Brown, Myles] Dana Farber Canc Inst, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02115 USA. [Torres-Arzayus, Maria I.; Brown, Myles] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Egan, Sean E.] Univ Toronto, Dept Med Genet, Toronto, ON M5R 0A3, Canada. [Rosen, Jeffrey M.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. RP Perou, CM (reprint author), Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. EM cperou@med.unc.edu OI Brown, Myles/0000-0002-8213-1658; Perou, Charles/0000-0001-9827-2247 FU NCI [P50-CA58223, P01 CA080111]; Department of Defense [W81XWH-12-1-0107]; NIEHS [T32-ES07017]; Canadian Breast Cancer Research Foundation; Breast Cancer Research Foundation; [RO1-CA138255]; [RO1-CA148761] FX We would like to thank the following labs for generously donating tumor samples for this project: Pamela Cowin (New York University), Yi Li (Baylor), Stuart Orkin (Harvard), Robert Schreiber (Washington University), Harold Varmus (NIH), and Yue Xiong (UNC). We would also like to thank the Perou lab and LW Pfefferle for helpful suggestions and review of the manuscript. This study was supported by funds from the following sources: NCI P50-CA58223 Breast SPORE program (CMP), RO1-CA138255 (CMP), RO1-CA148761 (CMP), Department of Defense W81XWH-12-1-0107 (CMP and GMW), NIEHS T32-ES07017 (ADP), NCI P01 CA080111 (MB), the Canadian Breast Cancer Research Foundation (SEE), and the Breast Cancer Research Foundation (CMP). NR 60 TC 40 Z9 40 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2013 VL 14 IS 11 AR R125 DI 10.1186/gb-2013-14-11-r125 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 302PA UT WOS:000330616200004 PM 24220145 ER PT J AU Urdaneta, RA Daher, S Leary, J Emanuel, KM Chuang, SK AF Urdaneta, Rainier A. Daher, Shadi Leary, Joseph Emanuel, Kimberly M. Chuang, Sung-Kiang TI The Survival of Ultrashort Locking-Taper Implants SO IMPLANTOLOGIE LA German DT Article DE dental implants; implant length; retrospective cohort study; short implants; single-tooth implants ID RETAINED MANDIBULAR OVERDENTURES; MULTICENTER CLINICAL-TRIAL; DENTAL IMPLANTS; FOLLOW-UP; ROUGH-SURFACE; RISK-FACTORS; PROSTHESES; RATIOS; RESTORATIONS; EDENTULISM AB Purpose: To evaluate the performance of 5-mm-long implants. Materials and Methods: A retrospective cohort study was conducted between January 2008 and December 2009. The sample was composed of patients who had received at least one 5-mm-wide, hydroxyapatite-coated Bicon implant. The outcome variable was implant failure. Descriptive statistics and univariate and multivariate Cox proportional hazards regression models, adjusted for multiple implants in the same patient, were utilized to identify predictors of dental implant failure. Results: Two hundred ninety-one subjects who received 410 locking-taper implants were followed for an average of 20 months. Of these, 211 were ultrashort implants (57 were 5 x 5.0 mm and 154 were 5 x 6.0 mm) and 199 were short implants (5 x 8.0 mm). Three hundred twenty-two implants (93.4 %) were restored with single crowns. There was a higher proportion of ultrashort single-tooth implants (94.6 %) as compared to short single-tooth implants (92.2 %). Nine implants failed, for a cumulative survival rate of 97.5 %. Of the failed implants, five were ultrashort (all 5 x 6.0 mm) and four were short. No failures were documented for 5-x 5.0-mm ultrashort implants. There was no statistically significant difference (P = .68) in the Kaplan-Meier survival rates of ultrashort implants (97.6 %) and short implants (95.2 %). After adjusting for other covariates in a multivariate model, implant length was not associated with implant failure (P = .49). Conclusions: The survival of ultrashort (5- and 6-mm) implants was comparable to that of short (8-mm) implants. C1 [Urdaneta, Rainier A.; Daher, Shadi; Leary, Joseph; Emanuel, Kimberly M.] Implant Dent Ctr, Boston, MA 02130 USA. [Chuang, Sung-Kiang] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Chuang, Sung-Kiang] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Urdaneta, RA (reprint author), Implant Dent Ctr, Boston, MA 02130 USA. EM rainieru@yahoo.com NR 37 TC 0 Z9 0 U1 0 U2 2 PU QUINTESSENZ VERLAGS-GMBH PI BERLIN PA IFENPFAD 2-4, BERLIN, 12107, GERMANY SN 0943-9692 J9 IMPLANTOLOGIE JI Implantologie PY 2013 VL 21 IS 3 BP 279 EP 292 PG 14 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA AA3MB UT WOS:000330995500005 ER PT J AU Gobin, RL Iverson, KM Mitchell, K Vaughn, R Resick, PA AF Gobin, Robyn L. Iverson, Katherine M. Mitchell, Karen Vaughn, Rachel Resick, Patricia A. TI The Impact of Childhood Maltreatment on PTSD Symptoms Among Female Survivors of Intimate Partner Violence SO VIOLENCE AND VICTIMS LA English DT Article DE domestic violence; childhood maltreatment; PTSD; mediation; structural equation modeling ID POSTTRAUMATIC-STRESS-DISORDER; FAMILY VIOLENCE; SEXUAL-ABUSE; SELF-REPORT; WOMEN; HEALTH; RISK; VICTIMIZATION; PREVALENCE; SAMPLE AB Objective: Intimate partner violence (IPV) survivors often report histories of childhood maltreatment, yet the unique contributions of childhood maltreatment on IPV survivors' distinct posttraumatic stress disorder (PTSD) symptoms remain inadequately understood. Method: Using interview and self-report measures, we examined IPV as a potential-mediator of the association between childhood maltreatment and severity of PTSD symptom clusters (reexperiencing, avoidance, numbing, and hyperarousal) among a sample of 425 women seeking help for recent IPV. Results: Structural equation modeling demonstrated that while both childhood maltreatment and IPV were both positively associated with PTSD symptom clusters, IPV did not mediate the association between childhood maltreatment and severity of PTSD symptom clusters among acute IPV survivors. Conclusions: Childhood maltreatment has persistent effects on the PTSD symptoms of IPV survivors, suggesting that child maltreatment may need to be addressed in addition to IPV during PTSD treatment. C1 [Gobin, Robyn L.; Vaughn, Rachel] VA Boston Healthcare Syst, Boston, MA USA. [Gobin, Robyn L.; Iverson, Katherine M.; Mitchell, Karen; Resick, Patricia A.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Gobin, Robyn L.] Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [Iverson, Katherine M.; Mitchell, Karen; Resick, Patricia A.] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA USA. [Resick, Patricia A.] Boston Univ, Sch Med, Dept Psychol, Boston, MA 02215 USA. RP Gobin, RL (reprint author), VA San Diego Healthcare Syst, 8810 Rio San Diego Dr 116A4Z, San Diego, CA 92108 USA. EM Robyn.Gobin@va.gov FU NIMH NIH HHS [1-R01-MH55542] NR 54 TC 2 Z9 2 U1 3 U2 6 PU SPRINGER PUBLISHING CO PI NEW YORK PA 11 WEST 42ND STREET, NEW YORK, NY 10036 USA SN 0886-6708 EI 1945-7073 J9 VIOLENCE VICTIMS JI Violence Vict. PY 2013 VL 28 IS 6 BP 984 EP 999 DI 10.1891/0886-6708.VV-D-12-00090 PG 16 WC Criminology & Penology SC Criminology & Penology GA 301DR UT WOS:000330513500005 PM 24547676 ER PT J AU Mitchell, MB Miller, LS Woodard, JL Davey, A Martin, P Poon, LW AF Mitchell, Meghan B. Miller, L. Stephen Woodard, John L. Davey, Adam Martin, Peter Poon, Leonard W. CA Georgia Centenarian Study TI Norms from the Georgia Centenarian Study: Measures of verbal abstract reasoning, fluency, memory, and motor function SO AGING NEUROPSYCHOLOGY AND COGNITION LA English DT Article DE Centenarians; normative; cognition; oldest old; Georgia Centenarian Study; Memory ID DEMENTIA AB We previously presented normative data from a relatively large, population-based sample (n = 244) of centenarians and a reference group of octogenarians (n = 80) for several brief, global neurocognitive tasks adapted for use for older adults with physical and sensory limitations (Miller et al., 2010, Neuropsychological, Development, and Cognition. Section B: Aging, Neuropsychology and Cognition, 17, 575). Here, we present additional normative data on several domain-specific tasks from these samples from Phase III of the Georgia Centenarian Study, including measures of verbal abstract reasoning, fluency, memory, and motor function. Expected age differences were demonstrated across all cognitive measures, and, consistent with our previous findings, centenarians showed a stronger association between age and performance. Normative tables are presented unweighted as well as population-weighted, and stratified by age and education level. These findings offer a unique contribution to the literature on cognitive aging, as normative performance in this age group is understudied and largely unavailable to clinicians and researchers. C1 [Mitchell, Meghan B.] Edith Nourse Rogers Mem Vet Hosp, Geriatr Res Educ Clin Ctr, Bedford, MA USA. [Mitchell, Meghan B.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Miller, L. Stephen] Univ Georgia, Dept Psychol, Athens, GA 30602 USA. [Woodard, John L.] Wayne State Univ, Dept Psychol, Detroit, MI 48202 USA. [Davey, Adam] Temple Univ, Philadelphia, PA 19122 USA. [Martin, Peter] Iowa State Univ, Ames, IA USA. [Poon, Leonard W.] Univ Georgia, Inst Gerontol, Athens, GA 30602 USA. RP Miller, LS (reprint author), Univ Georgia, Dept Psychol, 110 Hooper St,Rm 163 Psychol Bldg, Athens, GA 30602 USA. EM lsmiller@uga.edu OI Woodard, John/0000-0001-9196-3336 NR 13 TC 4 Z9 4 U1 2 U2 5 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1382-5585 EI 1744-4128 J9 AGING NEUROPSYCHOL C JI Aging Neuropsychol. Cogn. PY 2013 VL 20 IS 5 BP 620 EP 637 DI 10.1080/13825585.2012.761671 PG 18 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA 298SB UT WOS:000330343600007 ER PT J AU Bangsberg, DR Mills, EJ AF Bangsberg, David R. Mills, Edward J. TI Long-term adherence to antiretroviral therapy in resource-limited settings: a bitter pill to swallow SO ANTIVIRAL THERAPY LA English DT Editorial Material ID SUB-SAHARAN AFRICA; INHIBITOR THERAPY; SUPPRESSION; RISK; FACILITATORS; METAANALYSIS; DURATION; BARRIERS AB Adherence to antiretroviral therapy is an important predictor of long-term treatment success. Adherence can be differentiated between early adherence challenges, that are about integrating pill-taking into daily life, and long-term adherence, where patients struggle to maintain clinical connections and interrupt clinical care and medication use. In resource-limited settings, treatment interruptions may be more useful predictors of patient outcome than pill-taking alone. Interventions that are aimed at providing support to patients and their individual challenges to prevent interruptions in treatment and care may have a greater impact over time on clinically important outcomes than interventions targeted only at pill-taking behaviours. C1 [Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA. [Bangsberg, David R.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Mills, Edward J.] Univ Ottawa, Fac Hlth Sci, Ottawa, ON, Canada. [Mills, Edward J.] Stanford Univ, Stanford Prevent Res Ctr, Stanford, CA 94305 USA. RP Mills, EJ (reprint author), Univ Ottawa, Fac Hlth Sci, Ottawa, ON, Canada. EM edward.mills@uottawa.ca NR 28 TC 9 Z9 9 U1 1 U2 1 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 2013 VL 18 IS 1 BP 25 EP 28 DI 10.3851/IMP2536 PG 4 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 287XP UT WOS:000329575900003 PM 23358421 ER PT J AU Zheng, L Bosch, RJ Chan, ES Read, S Kearney, M Margolis, DM Mellors, JW Eron, JJ Gandhi, RT AF Zheng, Lu Bosch, Ronald J. Chan, Ellen S. Read, Sarah Kearney, Mary Margolis, David M. Mellors, John W. Eron, Joseph J. Gandhi, Rajesh T. CA AIDS Clinical Trials Grp ACTG A524 TI Predictors of residual viraemia in patients on long-term suppressive antiretroviral therapy SO ANTIVIRAL THERAPY LA English DT Article ID IMMUNE ACTIVATION; HIV BURDEN; T-CELLS; GUT; INFECTION; TRIALS; PLASMA; RNA AB Background: HIV-1-infected individuals with plasma RNA<50 copies/ml on antiretroviral therapy (ART) may have residual, low-level viraemia detectable by PCR assays that are able to detect a single copy of viral RNA (single-copy assay [SCA]). The clinical predictors of residual viraemia in patients on long-term suppressive ART are not yet fully understood. Methods: We evaluated factors associated with residual viraemia in patients on suppressive ART who underwent screening for a raltegravir intensification trial (ACTG A5244). The screened population was HIV-1-infected adults receiving ART for >= 12 months with pre-ART HIV-1 RNA>100,000 copies/ml and on-therapy RNA levels below detection limits of commercial assays for >= 6 months. Results: Of 103 patients eligible for analysis, the median age was 46 years and the median duration of viral suppression was 4.8 years. 62% had detectable viraemia (> 0.2 copies/ml) by SCA (median 0.2 copies/ml, IQR < 0.2-1.8). Younger patients had lower HIV-1 RNA levels than older individuals (r=0.27, P=0.005). Patients with virological suppression on ART for 2 years or less had higher residual viraemia than those with suppression for > 2 years (median 2.3 versus 0.2 copies/ml; P=0.016). Conclusions: Among HIV-1-infected patients with pre-ART HIV-1 RNA>100,000 copies/ml, residual viraemia was detectable in the majority (62%) despite many years of suppressive ART. Higher level viraemia was associated with older age and < 2 years of virological suppression on ART. These findings should help in the selection of candidates for clinical trials of interventions designed to eliminate residual viraemia. C1 [Zheng, Lu; Bosch, Ronald J.; Chan, Ellen S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Read, Sarah] NIAID, Bethesda, MD 20892 USA. [Kearney, Mary] NCI, Frederick, MD 21701 USA. [Margolis, David M.; Eron, Joseph J.] Univ N Carolina, Chapel Hill, NC USA. [Mellors, John W.] Univ Pittsburgh, Pittsburgh, PA USA. [Gandhi, Rajesh T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gandhi, Rajesh T.] Ragon Inst, Boston, MA USA. RP Zheng, L (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM szheng@sdac.harvard.edu OI Margolis, David/0000-0001-5714-0002 FU National Institute of Allergy and Infectious Diseases [U01AI068636, AI 06834]; NIH [R01 AI066992-04A1, G08LM008830-01]; Harvard University Center for AIDS Research [NIH 2P30 AI060354-06]; Tobira; GSK/ViiV through the University of North Carolina; [NIH U01 AI 694722] FX The project was supported by award number U01AI068636 from the National Institute of Allergy and Infectious Diseases. The project was also supported by a grant from the National Institute of Allergy and Infectious Diseases to the Statistical and Data Analysis Center (AI 06834). RTG is supported by NIH R01 AI066992-04A1 and NIH G08LM008830-01 and by grants to the AIDS Clinical Trials Group (NIH U01 AI 694722) and the Harvard University Center for AIDS Research (NIH 2P30 AI060354-06). The results of this analysis were previously presented at the XVII International AIDS Conference (Mexico City, Mexico) on 3-8 August 2008.; JWM is a consultant for Gilead Sciences and RFS Pharma and owns shares in RFS Pharma. JJE is a consultant for Merck, GSK/ViiV, Gilead, Tibotec and Bristol-Myers Squibb. He also receives research support from Tobira and GSK/ViiV through the University of North Carolina. NR 14 TC 7 Z9 7 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 2013 VL 18 IS 1 BP 39 EP 43 DI 10.3851/IMP2323 PG 5 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 287XP UT WOS:000329575900005 PM 22914318 ER PT J AU Anglaret, X Scott, CA Walensky, RP Ouattara, E Losina, E Moh, R Becker, JE Uhler, L Danel, C Messou, E Eholie, S Freedberg, KA AF Anglaret, Xavier Scott, Callie A. Walensky, Rochelle P. Ouattara, Eric Losina, Elena Moh, Raoul Becker, Jessica E. Uhler, Lauren Danel, Christine Messou, Eugene Eholie, Serge Freedberg, Kenneth A. TI Could early antiretroviral therapy entail more risks than benefits in sub-Saharan African HIV-infected adults? A model-based analysis SO ANTIVIRAL THERAPY LA English DT Article ID CD4 CELL COUNTS; COTE-DIVOIRE; COST-EFFECTIVENESS; RANDOMIZED-TRIAL; VIROLOGICAL SUPPRESSION; WEST-AFRICA; INITIATION; MORTALITY; DISEASE; IMPACT AB Background: Initiation of antiretroviral therapy (ART) in all HIV-infected adults, regardless of CD4(+) T-cell count, is a proposed strategy for reducing HIV transmission. We investigated the conditions under which starting ART early could entail more risks than benefits for patients with high CD4(+) T-cell counts. Methods: We used a simulation model to compare ART initiation upon entry to care (`immediate ART') to initiation at CD4(+) T-cell count = 350 cells/mu l (`WHO 2010 ART') in African adults with CD4(+) T-cell counts > 500 cells/mu l. We varied inputs to determine the combination of parameters (population characteristics, conditions of care, treatment outcomes) that would result in higher 15-year mortality with immediate ART. Results: The 15-year mortality was 56.7% for WHO 2010 ART and 51.8% for immediate ART. In one-way sensitivity analysis, lower 15-year mortality was consistently achieved with immediate ART unless the rate of fatal ART toxicity was > 1.0/100 person-years, the rate of withdrawal from care was > 1.2-fold higher or the rate of ART failure due to poor adherence was > 4.3-fold higher on immediate than on WHO 2010 ART. In multi-way sensitivity analysis, immediate ART led to higher mortality when moderate rates of fatal ART toxicity (0.25/100 person-years) were combined with rates of withdrawal from care > 1.1-fold higher and rates of treatment failure > 2.1-fold higher on immediate than on WHO 2010 ART. Conclusions: In sub-Saharan Africa, ART initiation at entry into care would improve long-term survival of patients with high CD4(+) T-cell counts, unless it is associated with increased withdrawal from care and decreased adherence. In early ART trials, a focus on retention and adherence will be crucial. C1 [Anglaret, Xavier; Ouattara, Eric; Moh, Raoul; Danel, Christine] Univ Bordeaux, ISPED, Bordeaux, France. [Anglaret, Xavier; Ouattara, Eric; Moh, Raoul; Danel, Christine] INSERM, Ctr INSERM U897, Bordeaux, France. [Anglaret, Xavier; Ouattara, Eric; Moh, Raoul; Danel, Christine; Messou, Eugene; Eholie, Serge] CHU Treichville, Programme PAC CI, Abidjan, Cote Ivoire. [Scott, Callie A.; Walensky, Rochelle P.; Losina, Elena; Becker, Jessica E.; Uhler, Lauren; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Dept Med, Med Practise Evaluat Ctr, Div Gen Med, Boston, MA 02114 USA. [Walensky, Rochelle P.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Dept Med, Practise Evaluat Ctr, Div Infect Dis, Boston, MA 02114 USA. [Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Walensky, Rochelle P.; Freedberg, Kenneth A.] Harvard Univ, Ctr AIDS Res, Cambridge, MA 02138 USA. [Walensky, Rochelle P.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Boston, MA USA. [Losina, Elena] Brigham & Womens Hosp, Dept Orthoped, Boston, MA 02115 USA. [Losina, Elena] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Moh, Raoul; Eholie, Serge] CHU Treichville, Serv Malad Infect & Trop, Abidjan, Cote Ivoire. [Freedberg, Kenneth A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Anglaret, X (reprint author), Univ Bordeaux, ISPED, Bordeaux, France. EM Xavier.Anglaret@isped.u-bordeaux2.fr RI Anglaret, Xavier/F-7333-2013; OI Walensky, Rochelle P./0000-0002-8795-379X FU Agence Nationale de Recherches sur le SIDA et les hepatites virales [ANRS 12136, ANRS 12212]; National Institute of Allergy and Infectious Diseases [R01 AI058736, K24 AI062476]; Doris Duke Charitable Foundation FX This study was funded by the Agence Nationale de Recherches sur le SIDA et les hepatites virales (ANRS 12136, ANRS 12212), the National Institute of Allergy and Infectious Diseases (R01 AI058736, K24 AI062476) and the Doris Duke Charitable Foundation. We extend our gratitude to the entire CEPAC-International team and investigators (Additional file 2). NR 42 TC 9 Z9 9 U1 0 U2 4 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 2013 VL 18 IS 1 BP 45 EP 55 DI 10.3851/IMP2231 PG 11 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 287XP UT WOS:000329575900006 PM 22809695 ER PT J AU Habel, LA Sakoda, LC Achacoso, N Ma, XJ Erlander, MG Sgroi, DC Fehrenbacher, L Greenberg, D Quesenberry, CP AF Habel, Laurel A. Sakoda, Lori C. Achacoso, Ninah Ma, Xiao-Jun Erlander, Mark G. Sgroi, Dennis C. Fehrenbacher, Louis Greenberg, Deborah Quesenberry, Charles P., Jr. TI HOXB13:IL17BR and molecular grade index and risk of breast cancer death among patients with lymph node-negative invasive disease SO BREAST CANCER RESEARCH LA English DT Article ID PROGNOSTIC UTILITY; EXPRESSION RATIO; GENE-EXPRESSION; TAMOXIFEN; IL17BR AB Introduction: Studies have shown that a two-gene ratio (HOXB13: IL17BR) and a five-gene (BUB1B, CENPA, NEK2, RACGAP1, RRM2) molecular grade index (MGI) are predictive of clinical outcomes among early-stage breast cancer patients. In an independent population of lymph node-negative breast cancer patients from a community hospital setting, we evaluated the performance of two risk classifiers that have been derived from these gene signatures combined, MGI+HOXB13:IL17BR and the Breast Cancer Index (BCI). Methods: A case-control study was conducted among 4,964 Kaiser Permanente patients diagnosed with node-negative invasive breast cancer from 1985 to 1994 who did not receive adjuvant chemotherapy. For 191 cases (breast cancer deaths) and 417 matched controls, archived tumor tissues were available and analyzed for expression levels of the seven genes of interest and four normalization genes by RT-PCR. Logistic regression methods were used to estimate the relative risk (RR) and 10-year absolute risk of breast cancer death associated with prespecified risk categories for MGI+HOXB13:IL17BR and BCI. Results: Both MGI+HOXB13:IL17BR and BCI classified over half of all ER-positive patients as low risk. The 10-year absolute risks of breast cancer death for ER-positive, tamoxifen-treated patients classified in the low-, intermediate-, and high-risk groups were 3.7% (95% confidence interval (CI) 1.9% to 5.4%), 5.9% (95% CI 3.0% to 8.6%), and 12.9% (95% CI 7.9% to 17.6%) by MGI+HOXB13: IL17BR and 3.5% (95% CI 1.9% to 5.1%), 7.0% (95% CI 3.8% to 10.1%), and 12.9% (95% CI 7.1% to 18.3%) by BCI. Those for ER-positive, tamoxifen-untreated patients were 5.7% (95% CI 4.0% to 7.4%), 13.8% (95% CI 8.4% to 18.9%), and 15.2% (95% CI 9.4% to 20.5%) by MGI+HOXB13:IL17BR and 5.1% (95% CI 3.6% to 6.6%), 18.6% (95% CI 10.8% to 25.7%), and 17.5% (95% CI 11.1% to 23.5%) by BCI. After adjusting for tumor size and grade, the RRs of breast cancer death comparing high-versus low-risk categories of both classifiers remained elevated but were attenuated for tamoxifen-treated and tamoxifen-untreated patients. Conclusion: Among ER-positive, lymph node-negative patients not treated with adjuvant chemotherapy, MGI+HOXB13:IL17BR and BCI were associated with risk of breast cancer death. Both risk classifiers appeared to provide risk information beyond standard prognostic factors. C1 [Habel, Laurel A.; Sakoda, Lori C.; Achacoso, Ninah; Quesenberry, Charles P., Jr.] Kaiser Permanente, Div Res, Oakland, CA 94612 USA. [Ma, Xiao-Jun; Erlander, Mark G.] bioTheranostics, San Diego, CA 92121 USA. [Sgroi, Dennis C.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. [Fehrenbacher, Louis] Kaiser Permanente Med Ctr, Dept Hematol Oncol, Vallejo, CA 94589 USA. [Greenberg, Deborah] Kaiser Permanente, TPMG Reg Lab, Berkeley, CA 94710 USA. RP Habel, LA (reprint author), Kaiser Permanente, Div Res, 2000 Broadway, Oakland, CA 94612 USA. EM laurel.habel@kp.org FU Avon Foundation; National Institute of Health [R01CA112021]; Department of Defense Breast Cancer Research Program [W81XWH-04-1-0606] FX We thank Kaiser Permanente patients, as well as personnel at the Permanente Medical Group Regional Laboratory and at Kaiser Permanente Medical Center pathology departments. Dr. Sgroi received support from the Avon Foundation (PI, Sgroi), National Institute of Health (R01CA112021; PI, Sgroi), and The Department of Defense Breast Cancer Research Program (W81XWH-04-1-0606). NR 17 TC 9 Z9 10 U1 0 U2 0 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. PY 2013 VL 15 IS 2 AR R24 DI 10.1186/bcr3402 PG 11 WC Oncology SC Oncology GA 302NU UT WOS:000330612000007 PM 23497539 ER PT J AU Oaklander, AL AF Oaklander, Anne Louise TI NEUROPATHIC ITCH SYNDROMES: OVERVIEW AND OPPORTUNITEES SO ACTA DERMATO-VENEREOLOGICA LA English DT Meeting Abstract C1 [Oaklander, Anne Louise] Harvard Univ, Sch Med, Dept Neurol, Nerve Injury Unit,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Oaklander, Anne Louise] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nerve Injury Unit,Dept Pathol Neuropathol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACTA DERMATO-VENEREOLOGICA PI UPPSALA PA TRADGARDSGATAN 14, UPPSALA, SE-753 09, SWEDEN SN 0001-5555 EI 1651-2057 J9 ACTA DERM-VENEREOL JI Acta Derm.-Venereol. PY 2013 VL 93 IS 5 BP 610 EP 610 PG 1 WC Dermatology SC Dermatology GA 298ME UT WOS:000330327200053 ER PT J AU Lang, M Treister, R Klein, M Oaklander, AL AF Lang, Magdalena Treister, Roi Klein, Max Oaklander, Anne Louise TI A PILOT STUDY OF EFFICACY OF REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION (RTMS) OF THE MOTOR CORTEX ON NEUROPATHIC ITCH SO ACTA DERMATO-VENEREOLOGICA LA English DT Meeting Abstract C1 [Lang, Magdalena; Treister, Roi; Klein, Max; Oaklander, Anne Louise] Massachusetts Gen Hosp, Dept Neurol, Nerve Injury Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACTA DERMATO-VENEREOLOGICA PI UPPSALA PA TRADGARDSGATAN 14, UPPSALA, SE-753 09, SWEDEN SN 0001-5555 EI 1651-2057 J9 ACTA DERM-VENEREOL JI Acta Derm.-Venereol. PY 2013 VL 93 IS 5 BP 617 EP 618 PG 2 WC Dermatology SC Dermatology GA 298ME UT WOS:000330327200080 ER PT J AU Elmariah, S Luo, TL Azimi, E Reddy, V Lerner, E AF Elmariah, Sarina Luo, Tuanlian Azimi, Ehsan Reddy, Vemuri Lerner, Ethan TI NEURAL RECRUITMENT AND ACTIVITY IS INTEGRAL TO THE PATHOGENESIS OF ATOPIC DERMATITIS SO ACTA DERMATO-VENEREOLOGICA LA English DT Meeting Abstract C1 [Elmariah, Sarina; Luo, Tuanlian; Azimi, Ehsan; Reddy, Vemuri; Lerner, Ethan] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACTA DERMATO-VENEREOLOGICA PI UPPSALA PA TRADGARDSGATAN 14, UPPSALA, SE-753 09, SWEDEN SN 0001-5555 EI 1651-2057 J9 ACTA DERM-VENEREOL JI Acta Derm.-Venereol. PY 2013 VL 93 IS 5 BP 620 EP 620 PG 1 WC Dermatology SC Dermatology GA 298ME UT WOS:000330327200090 ER PT J AU Elmariah, S Conniff, T Luo, T Azimi, E Reddy, V Wolpowitz, D Lerner, EA AF Elmariah, Sarina Conniff, Tara Luo, Tuanlian Azimi, Ehsan Reddy, Vermuri Wolpowitz, Deon Lerner, Ethan A. TI ALTERED CUTANEOUS INNERVATION IN PRURITIC DERMATOSES SO ACTA DERMATO-VENEREOLOGICA LA English DT Meeting Abstract C1 [Elmariah, Sarina; Luo, Tuanlian; Azimi, Ehsan; Reddy, Vermuri; Lerner, Ethan A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Conniff, Tara; Wolpowitz, Deon] Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACTA DERMATO-VENEREOLOGICA PI UPPSALA PA TRADGARDSGATAN 14, UPPSALA, SE-753 09, SWEDEN SN 0001-5555 EI 1651-2057 J9 ACTA DERM-VENEREOL JI Acta Derm.-Venereol. PY 2013 VL 93 IS 5 BP 623 EP 623 PG 1 WC Dermatology SC Dermatology GA 298ME UT WOS:000330327200102 ER PT J AU Azimi, E Elmariah, S Garibyan, L Lerner, EA AF Azimi, Ehsan Elmariah, Sarina Garibyan, Lilit Lerner, Ethan A. TI CHANGES IN THE MANIFESTATIONS OF SKIN DISEASE IN PATIENTS WITH NERVE DAMAGE SO ACTA DERMATO-VENEREOLOGICA LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACTA DERMATO-VENEREOLOGICA PI UPPSALA PA TRADGARDSGATAN 14, UPPSALA, SE-753 09, SWEDEN SN 0001-5555 EI 1651-2057 J9 ACTA DERM-VENEREOL JI Acta Derm.-Venereol. PY 2013 VL 93 IS 5 BP 627 EP 627 PG 1 WC Dermatology SC Dermatology GA 298ME UT WOS:000330327200116 ER PT J AU Azimi, E Reddy, VB Luo, TL Lerner, EA AF Azimi, Ehsan Reddy, V. B. Luo, Tuanlian Lerner, Ethan A. TI FICIN, A PLANT PROTEASE, IS A POTENT PRURITOGEN SO ACTA DERMATO-VENEREOLOGICA LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACTA DERMATO-VENEREOLOGICA PI UPPSALA PA TRADGARDSGATAN 14, UPPSALA, SE-753 09, SWEDEN SN 0001-5555 EI 1651-2057 J9 ACTA DERM-VENEREOL JI Acta Derm.-Venereol. PY 2013 VL 93 IS 5 BP 627 EP 627 PG 1 WC Dermatology SC Dermatology GA 298ME UT WOS:000330327200117 ER PT J AU Desbordes, G Li, A Loggia, M Kim, J Schalock, P Lerner, EA Tran, T Ring, J Rosen, B Kaptchuk, T Pfab, F Napadow, V AF Desbordes, Gaelle Li, Ang Loggia, Marco Kim, Jieun Schalock, Peter Lerner, Ethan A. Thanh Tran Ring, Johannes Rosen, Bruce Kaptchuk, Ted Pfab, Florian Napadow, Vitaly TI EVOKED ALLERGEN ITCH MODULATES BRAIN FUNCTIONAL CONNECTIVITY IN ATOPIC DERMATITIS PATIENTS SO ACTA DERMATO-VENEREOLOGICA LA English DT Meeting Abstract C1 [Desbordes, Gaelle; Li, Ang; Loggia, Marco; Kim, Jieun; Schalock, Peter; Lerner, Ethan A.; Thanh Tran; Napadow, Vitaly] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ring, Johannes; Rosen, Bruce; Pfab, Florian] Tech Univ Munich, D-80290 Munich, Germany. [Kaptchuk, Ted] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACTA DERMATO-VENEREOLOGICA PI UPPSALA PA TRADGARDSGATAN 14, UPPSALA, SE-753 09, SWEDEN SN 0001-5555 EI 1651-2057 J9 ACTA DERM-VENEREOL JI Acta Derm.-Venereol. PY 2013 VL 93 IS 5 BP 629 EP 629 PG 1 WC Dermatology SC Dermatology GA 298ME UT WOS:000330327200123 ER PT J AU Reddy, VB Elmariah, S Azimi, E Luo, TL Lerner, EA AF Reddy, V. B. Elmariah, Sarina Azimi, Ehsan Luo, Tuanlian Lerner, Ethan A. TI MECHANISMS OF ITCH: PROTEASES ACTIVATE MAS-RELATED G-PROTEIN COUPLED RECEPTORS SO ACTA DERMATO-VENEREOLOGICA LA English DT Meeting Abstract C1 [Reddy, V. B.; Elmariah, Sarina; Azimi, Ehsan; Luo, Tuanlian; Lerner, Ethan A.] Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACTA DERMATO-VENEREOLOGICA PI UPPSALA PA TRADGARDSGATAN 14, UPPSALA, SE-753 09, SWEDEN SN 0001-5555 EI 1651-2057 J9 ACTA DERM-VENEREOL JI Acta Derm.-Venereol. PY 2013 VL 93 IS 5 BP 635 EP 635 PG 1 WC Dermatology SC Dermatology GA 298ME UT WOS:000330327200148 ER PT J AU Bortnik, KE Horner, MD Bachman, DL AF Bortnik, Kirsty E. Horner, Michael David Bachman, David L. TI Performance on Standard Indexes of Effort Among Patients with Dementia SO APPLIED NEUROPSYCHOLOGY-ADULT LA English DT Article DE dementia; effort; geriatric; symptom validity testing ID SYMPTOM VALIDITY TEST; MEMORY MALINGERING TOMM; NEUROPSYCHOLOGICAL STATUS RBANS; DIAGNOSTIC-CRITERIA; REPEATABLE BATTERY; CLASSIFICATION ACCURACY; INTERNATIONAL WORKSHOP; COGNITIVELY INTACT; VASCULAR DEMENTIA; GERIATRIC SAMPLE AB Assessment of response validity is an integral part of neuropsychological practice. Although many studies have demonstrated the efficacy of stand alone and embedded effort measures in a variety of medical and compensation-seeking contexts, much less is known about the robustness of these measures in elderly populations, particularly in patients with dementia. Although older adults may be viewed as less likely to intentionally feign symptoms for an external gain, there are a variety of other factors that could result in suboptimal effort, including fatigue, lack of interest or cooperation in the testing process, or failure to fully appreciate the implications of the assessment on treatment care and outcome. The current study examined the clinical utility of several stand alone and embedded effort measures including the Repeatable Battery for the Assessment of Neuropsychological Status Effort Index, Trail-Making Test Ratio, Rey 15-Item Test, and the Test of Memory Malingering in a sample of patients with dementia. Results found that the majority of effort indexes demonstrated unacceptably high false-positive error rates with specificity levels as high as 83%. These findings demonstrate the need for caution in interpreting effort measure performance in dementia samples due to the fact that despite their best effort, many patients with dementia fail effort measures and are at risk for being misclassified. C1 [Bortnik, Kirsty E.] Med Univ S Carolina, Fuller Grad Sch Psychol, Charleston, SC 29425 USA. [Bortnik, Kirsty E.; Horner, Michael David; Bachman, David L.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Horner, Michael David; Bachman, David L.] Med Univ S Carolina, Neuropsychol Clin, Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Bortnik, KE (reprint author), Columbia Univ, Med Ctr, Neurol Inst, 710 W 168th St, New York, NY 10032 USA. EM kbortnik@gmail.com NR 60 TC 8 Z9 8 U1 3 U2 9 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0908-4282 EI 1532-4826 J9 APPL NEUROPSYCH-ADUL JI Appl. Neuropsychol.-Adult PY 2013 VL 20 IS 4 BP 233 EP 242 DI 10.1080/09084282.2012.695757 PG 10 WC Clinical Neurology; Psychology SC Neurosciences & Neurology; Psychology GA 298ST UT WOS:000330345400001 ER PT J AU Spencer, TJ Brown, A Seidman, LJ Valera, EM Makris, N Lomedico, A Faraone, SV Biederman, J AF Spencer, Thomas J. Brown, Ariel Seidman, Larry J. Valera, Eve M. Makris, Nikos Lomedico, Alexandra Faraone, Stephen V. Biederman, Joseph TI Effect of Psychostimulants on Brain Structure and Function in ADHD: A Qualitative Literature Review of Magnetic Resonance Imaging-Based Neuroimaging Studies SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; METHYLPHENIDATE TREATMENT; STIMULANT MEDICATION; WORKING-MEMORY; BASAL GANGLIA; UNITED-STATES; ADULT ADHD; CHILDREN; MRI AB Objective: To evaluate the impact of therapeutic oral doses of stimulants on the brains of ADHD subjects as measured by magnetic resonance imaging (MRI)-based neuroimaging studies (morphometric, functional, spectroscopy). Data Sources: We searched PubMed and ScienceDirect through the end of calendar year 2011 using the keywords (1) psychostimulants or methylphenidate or amphetamine, and (2) neuroimaging or MRI or fMRI, and (3) ADHD or ADD or attention-deficit/hyperactivity disorder or attention deficit hyperactivity disorder. Study Selection: We included only English language articles with new data from case-control or placebo controlled studies that examined attention-deficit/hyperactivity disorder (ADHD) subjects on and off psychostimulants (as well as 5 relevant review articles). Data Extraction: We combined details of study design and medication effects in each imaging modality. Results: We found 29 published studies that met our criteria. These included 6 structural MRI, 20 functional MRI studies, and 3 spectroscopy studies. Methods varied widely in terms of design, analytic technique, and regions of the brain investigated. Despite heterogeneity in methods, however, results were consistent. With only a few exceptions, the data on the effect of therapeutic oral doses of stimulant medication suggest attenuation of structural and functional alterations found in unmedicated ADHD subjects relative to findings in controls. Conclusions: Despite the inherent limitations and heterogeneity of the extant MRI literature, our review suggests that therapeutic oral doses of stimulants decrease alterations in brain structure and function in subjects with ADHD relative to unmedicated subjects and controls. These medication-associated brain effects parallel, and may underlie, the well-established clinical benefits. C1 [Spencer, Thomas J.; Brown, Ariel; Seidman, Larry J.; Valera, Eve M.; Lomedico, Alexandra; Biederman, Joseph] Harvard Univ, Sch Med, Clin & Res Program Pediat Psychopharmacol, Boston, MA USA. RP Spencer, TJ (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, 55 Fruit St WRN 705, Boston, MA 02114 USA. EM Spencer@helix.mgh.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU Pediatric Psychopharmacology Council Fund, Massachusetts General Hospital, Boston FX This study was supported in part by the Pediatric Psychopharmacology Council Fund, Massachusetts General Hospital, Boston. NR 54 TC 29 Z9 30 U1 6 U2 34 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2013 VL 74 IS 9 BP 902 EP 917 DI 10.4088/JCP.12r08287 PG 16 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 296LA UT WOS:000330185300008 PM 24107764 ER PT S AU Humbert, M Montani, D Evgenov, OV Simonneau, G AF Humbert, Marc Montani, David Evgenov, Oleg V. Simonneau, Gerald BE Humbert, M Evgenov, OV Stasch, JP TI Definition and Classification of Pulmonary Hypertension SO PHARMACOTHERAPY OF PULMONARY HYPERTENSION SE Handbook of Experimental Pharmacology LA English DT Article; Book Chapter DE Pulmonary arterial hypertension; Pulmonary artery pressure; Pulmonary hypertension; Right heart catheterization ID SICKLE-CELL-DISEASE; GLYCOGEN-STORAGE-DISEASE; CONNECTIVE-TISSUE DISEASES; CHRONIC HEART-FAILURE; OF-THE-LITERATURE; ARTERIAL-HYPERTENSION; VENOOCCLUSIVE DISEASE; CLINICAL CHARACTERISTICS; SYSTEMIC-SCLEROSIS; PROGNOSTIC-FACTORS AB Pulmonary hypertension is defined as an increase of mean pulmonary arterial pressure >= 25 mmHg at rest as assessed by right heart catheterization. According to different combinations of values of pulmonary wedge pressure, pulmonary vascular resistance and cardiac output, a hemodynamic classification of pulmonary hypertension has been proposed. Of major importance is the pulmonary wedge pressure which allows to distinguish pre-capillary (pulmonary wedge pressure <= 15 mmHg) and post-capillary (pulmonary wedge pressure > 15 mmHg) pulmonary hypertension. Precapillary pulmonary hypertension includes the clinical groups 1 (pulmonary arterial hypertension), 3 (pulmonary hypertension due to lung diseases and/or hypoxia), 4 (chronic thrombo-embolic pulmonary hypertension) and 5 (pulmonary hypertension with unclear and/or multifactorial mechanisms). Post-capillary pulmonary hypertension corresponds to the clinical group 2 (pulmonary hypertension due to left heart diseases). C1 [Humbert, Marc; Montani, David; Simonneau, Gerald] Univ Paris Sud, Fac Med, F-94275 Le Kremlin Bicetre, France. [Humbert, Marc; Montani, David; Simonneau, Gerald] Ctr Chirurg Marie Lannelongue, Inserm U999, Le Plessis Robinson, France. [Humbert, Marc; Montani, David; Simonneau, Gerald] Hop Bicetre, AP HP, Serv Pneumol & Reanimat Resp, F-94270 Le Kremlin Bicetre, France. [Evgenov, Oleg V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. RP Humbert, M (reprint author), Univ Paris Sud, Fac Med, F-94275 Le Kremlin Bicetre, France. EM marc.humbert@abc.aphp.fr OI Montani, David/0000-0002-9358-6922 NR 113 TC 5 Z9 5 U1 0 U2 6 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0171-2004 BN 978-3-642-38663-3; 978-3-642-38664-0 J9 HANDB EXP PHARMACOL JI Handb. Exp. Pharmacol. PY 2013 VL 218 BP 3 EP 29 DI 10.1007/978-3-642-38664-0_1 D2 10.1007/978-3-642-38664-0 PG 27 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BJN29 UT WOS:000329227200002 PM 24092334 ER PT S AU Humbert, M Evgenov, OV Stasch, JP AF Humbert, Marc Evgenov, Oleg V. Stasch, Johannes-Peter BE Humbert, M Evgenov, OV Stasch, JP TI Pharmacotherapy of Pulmonary Hypertension Preface SO PHARMACOTHERAPY OF PULMONARY HYPERTENSION SE Handbook of Experimental Pharmacology LA English DT Editorial Material; Book Chapter C1 [Humbert, Marc] Univ Paris Sud, Fac Med, F-94275 Le Kremlin Bicetre, France. [Evgenov, Oleg V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dep Anasthesia & Crit Care, Boston, MA USA. [Stasch, Johannes-Peter] Bayer Pharma AG, Cardiovasc Res, Wuppertal, Germany. RP Humbert, M (reprint author), Univ Paris Sud, Fac Med, F-94275 Le Kremlin Bicetre, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0171-2004 BN 978-3-642-38663-3; 978-3-642-38664-0 J9 HANDB EXP PHARMACOL JI Handb. Exp. Pharmacol. PY 2013 VL 218 BP V EP VI D2 10.1007/978-3-642-38664-0 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BJN29 UT WOS:000329227200001 ER PT S AU Stasch, JP Evgenov, OV AF Stasch, Johannes-Peter Evgenov, Oleg V. BE Humbert, M Evgenov, OV Stasch, JP TI Soluble Guanylate Cyclase Stimulators in Pulmonary Hypertension SO PHARMACOTHERAPY OF PULMONARY HYPERTENSION SE Handbook of Experimental Pharmacology LA English DT Article; Book Chapter DE Pulmonary hypertension; Nitric oxide; Soluble guanylate cyclase; sGC stimulator; Riociguat ID VASCULAR SMOOTH-MUSCLE; NO-INDEPENDENT STIMULATORS; RIOCIGUAT TRIAL LEPHT; NITRIC-OXIDE RECEPTOR; YC-1 BINDING-SITE; ARTERIAL-HYPERTENSION; BAY 41-2272; CYCLIC-GMP; OXIDATIVE STRESS; FUNCTIONAL-CHARACTERIZATION AB Soluble guanylate cyclase (sGC) is a key enzyme in the nitric oxide (NO) signalling pathway. On binding of NO to its prosthetic haem group, sGC catalyses the synthesis of the second messenger cyclic guanosine monophosphate (cGMP), which promotes vasodilation and inhibits smooth muscle proliferation, leukocyte recruitment, platelet aggregation and vascular remodelling through a number of downstream mechanisms. The central role of the NO-sGC-cGMP pathway in regulating pulmonary vascular tone is demonstrated by the dysregulation of NO production, sGC activity and cGMP degradation in pulmonary hypertension (PH). The sGC stimulators are novel pharmacological agents that directly stimulate sGC, both independently of NO and in synergy with NO. Optimisation of the first sGC stimulator, YC-1, led to the development of the more potent and more specific sGC stimulators, BAY 41-2272, BAY 41-8543 and riociguat (BAY 63-2521). Other sGC stimulators include CFM-1571, BAY 60-4552, vericiguat (BAY 1021189), the acrylamide analogue A-350619 and the aminopyrimidine analogues. BAY 41-2272, BAY 41-8543 and riociguat induced marked dose-dependent reductions in mean pulmonary arterial pressure and vascular resistance with a concomitant increase in cardiac output, and they also reversed vascular remodelling and right heart hypertrophy in several experimental models of PH. Riociguat is the first sGC stimulator that has entered clinical development. Clinical trials have shown that it significantly improves pulmonary vascular haemodynamics and increases exercise ability in patients with pulmonary arterial hypertension (PAH), chronic thromboembolic PH and PH associated with interstitial lung disease. Furthermore, riociguat reduces mean pulmonary arterial pressure in patients with PH associated with chronic obstructive pulmonary disease and improves cardiac index and pulmonary vascular resistance in patients with PH associated with left ventricular systolic dysfunction. These promising results suggest that sGC stimulators may constitute a valuable new therapy for PH. Other trials of riociguat are in progress, including a study of the haemodynamic effects and safety of riociguat in patients with PH associated with left ventricular diastolic dysfunction, and long-term extensions of the phase 3 trials investigating the efficacy and safety of riociguat in patients with PAH and chronic thromboembolic PH. Finally, sGC stimulators may also have potential therapeutic applications in other diseases, including heart failure, lung fibrosis, scleroderma and sickle cell disease. C1 [Stasch, Johannes-Peter] Bayer Pharma AG, Cardiol Res, D-42096 Wuppertal, Germany. [Stasch, Johannes-Peter] Univ Halle Wittenberg, Inst Pharm, D-06108 Halle, Saale, Germany. [Evgenov, Oleg V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Stasch, JP (reprint author), Bayer Pharma AG, Cardiol Res, Aprather Weg 18a, D-42096 Wuppertal, Germany. EM johannes-peter.stasch@bayer.com; oevgenov@partners.org NR 149 TC 46 Z9 47 U1 0 U2 7 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0171-2004 BN 978-3-642-38663-3; 978-3-642-38664-0 J9 HANDB EXP PHARMACOL JI Handb. Exp. Pharmacol. PY 2013 VL 218 BP 279 EP 313 DI 10.1007/978-3-642-38664-0_12 D2 10.1007/978-3-642-38664-0 PG 35 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BJN29 UT WOS:000329227200013 PM 24092345 ER PT J AU Knaul, FM Chabner, BA AF Knaul, Felicia M. Chabner, Bruce A. TI Announcing a New Section: Global Health and Cancer SO ONCOLOGIST LA English DT Editorial Material C1 [Knaul, Felicia M.] Harvard Global Equ Initiat, Boston, MA 02115 USA. [Chabner, Bruce A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Knaul, Felicia M.] Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02115 USA. [Chabner, Bruce A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Knaul, FM (reprint author), Harvard Global Equ Initiat, 651 Huntington Ave,FXB Bldg 632, Boston, MA 02115 USA. EM felicia_knaul@harvard.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2013 VL 18 SU S BP 1 EP 2 DI 10.1634/theoncologist.2013-0158 PG 2 WC Oncology SC Oncology GA 274LR UT WOS:000328608400001 PM 24334475 ER PT J AU Bhatt, AS AF Bhatt, Ami S. TI Bacterial Genomics in Transplant-Related Colitis SO ONCOLOGIST LA English DT Meeting Abstract C1 [Bhatt, Ami S.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2013 VL 18 SU 1 MA 7 BP S3 EP S3 PG 1 WC Oncology SC Oncology GA 274LU UT WOS:000328608700008 ER PT J AU Carlson, J AF Carlson, Jonathan TI "Click" Chemistry In Vivo: New Tools for Molecular Imaging SO ONCOLOGIST LA English DT Meeting Abstract C1 [Carlson, Jonathan] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2013 VL 18 SU 1 MA 8 BP S4 EP S4 PG 1 WC Oncology SC Oncology GA 274LU UT WOS:000328608700009 ER PT J AU Farago, A AF Farago, Anna TI Leveraging Genetically Engineered Mouse Models of Small Cell Lung Cancer for Advanced Therapeutic Studies SO ONCOLOGIST LA English DT Meeting Abstract C1 [Farago, Anna] Dana Farber Canc Inst, Boston, MA 02115 USA. [Farago, Anna] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2013 VL 18 SU 1 MA 9 BP S4 EP S4 PG 1 WC Oncology SC Oncology GA 274LU UT WOS:000328608700010 ER PT J AU Fisher, DE AF Fisher, David E. TI Multiple Roles of MITF SO ONCOLOGIST LA English DT Meeting Abstract C1 [Fisher, David E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2013 VL 18 SU 1 MA 12 BP S5 EP S5 PG 1 WC Oncology SC Oncology GA 274LU UT WOS:000328608700013 ER PT J AU Flaherty, K AF Flaherty, Keith TI Next Steps in Melanoma Treatment SO ONCOLOGIST LA English DT Meeting Abstract C1 [Flaherty, Keith] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2013 VL 18 SU 1 MA 11 BP S5 EP S5 PG 1 WC Oncology SC Oncology GA 274LU UT WOS:000328608700012 ER PT J AU Huang, F AF Huang, Franklin TI TERT Promoter Mutations in Cancer SO ONCOLOGIST LA English DT Meeting Abstract C1 [Huang, Franklin] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2013 VL 18 SU 1 MA 10 BP S4 EP S4 PG 1 WC Oncology SC Oncology GA 274LU UT WOS:000328608700011 ER PT J AU Lane, A AF Lane, Andrew TI Histone H3K27 Demethylases as a Therapeutic Target in Polysomy 21 Leukemia SO ONCOLOGIST LA English DT Meeting Abstract C1 [Lane, Andrew] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2013 VL 18 SU 1 MA 6 BP S3 EP S3 PG 1 WC Oncology SC Oncology GA 274LU UT WOS:000328608700007 ER PT J AU Lee, R AF Lee, Richard TI CTC Developments SO ONCOLOGIST LA English DT Meeting Abstract C1 [Lee, Richard] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2013 VL 18 SU 1 MA 15 BP S6 EP S6 PG 1 WC Oncology SC Oncology GA 274LU UT WOS:000328608700016 ER PT J AU Sequist, L AF Sequist, Lecia TI EGFR-Mutant Lung Cancer: New Drugs SO ONCOLOGIST LA English DT Meeting Abstract C1 [Sequist, Lecia] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2013 VL 18 SU 1 MA 1 BP S1 EP S1 PG 1 WC Oncology SC Oncology GA 274LU UT WOS:000328608700002 ER PT J AU Smith, MR AF Smith, Matthew R. TI Novel Agents in Advanced Disease SO ONCOLOGIST LA English DT Meeting Abstract C1 [Smith, Matthew R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2013 VL 18 SU 1 MA 17 BP S7 EP S7 PG 1 WC Oncology SC Oncology GA 274LU UT WOS:000328608700018 ER PT J AU Taplin, ME AF Taplin, Mary-Ellen TI Neoadjuvant Therapy SO ONCOLOGIST LA English DT Meeting Abstract C1 [Taplin, Mary-Ellen] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2013 VL 18 SU 1 MA 16 BP S6 EP S6 PG 1 WC Oncology SC Oncology GA 274LU UT WOS:000328608700017 ER PT J AU Ting, DT AF Ting, David Tsai TI Molecular Analysis of CTCs SO ONCOLOGIST LA English DT Meeting Abstract C1 [Ting, David Tsai] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2013 VL 18 SU 1 MA 13 BP S5 EP S5 PG 1 WC Oncology SC Oncology GA 274LU UT WOS:000328608700014 ER PT J AU Whetstine, J AF Whetstine, Johnathan TI Chromatin Modulators Provide a New Insight Into Cancer Genomes SO ONCOLOGIST LA English DT Meeting Abstract C1 [Whetstine, Johnathan] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PY 2013 VL 18 SU 1 MA 3 BP S1 EP S1 PG 1 WC Oncology SC Oncology GA 274LU UT WOS:000328608700004 ER PT J AU Torriani, M Zanni, MV Fitch, K Stavrou, E Bredella, MA Lim, R Cypess, AM Grinspoon, S AF Torriani, Martin Zanni, Markella V. Fitch, Kathleen Stavrou, Eleni Bredella, Miriam A. Lim, Ruth Cypess, Aaron M. Grinspoon, Steven TI Increased FDG uptake in association with reduced extremity fat in HIV patients SO ANTIVIRAL THERAPY LA English DT Article ID SUBCUTANEOUS ADIPOSE-TISSUE; CARDIOVASCULAR RISK; GLUCOSE-TRANSPORT; INFECTED PATIENTS; LIPODYSTROPHY; EXPRESSION; INFLAMMATION; LIPOATROPHY; ADIPOCYTES AB Background: HIV lipodystrophy - characterized by peripheral lipoatrophy, with or without central fat accumulation - confers increased metabolic risk. However, the functional activity of HIV lipodystrophic tissue in relation to metabolic risk has yet to be fully explored in vivo through the use of non-invasive imaging techniques. This study assesses the relationship between FDG uptake in various fat depots and metabolic/immune parameters among subjects with HIV lipodystrophy. Methods: Lipodystrophic men on antiretroviral therapy underwent whole-body F-18-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography scans and detailed metabolic/immune phenotyping. Results: FDG uptake in the subcutaneous adipose tissue (SAT) of the extremities (mean standardized uptake value [SUV] of the arm and leg SAT) was found to correlate with the degree of peripheral lipoatrophy (r=0.7; P=0.01). Extremity SAT FDG uptake was positively associated with homeostasis model assessment of insulin resistance (HOMA-IR; r=0.6; P=0.02) and fasting hyperinsulinaemia (r=0.7; P=0.01), while fat percentage of extremities was not. Furthermore, extremity SAT FDG uptake was significantly associated with CD4(+) T-cell count (r=0.6; P=0.05). In multivariate modelling for HOMA-IR, extremity SAT FDG uptake remained significant after controlling for body mass index and tumour necrosis factor-alpha (R-2 for model =0.71, P=0.02; SUV in the extremity SAT beta-estimate 12.3, P=0.009). Conclusions: In HIV lipodystrophic patients, extremity SAT FDG uptake is increased in association with reduced extremity fat and may contribute to insulin resistance. Non-invasive assessments of in situ inflammation using FDG-PET may usefully complement histological and gene expression analyses of metabolic dysregulation in peripheral fat among HIV-positive patients. C1 [Torriani, Martin; Bredella, Miriam A.] Massachusetts Gen Hosp, Div Musculoskeletal Imaging & Intervent, Boston, MA 02114 USA. [Torriani, Martin; Zanni, Markella V.; Fitch, Kathleen; Stavrou, Eleni; Bredella, Miriam A.; Lim, Ruth; Cypess, Aaron M.; Grinspoon, Steven] Harvard Univ, Sch Med, Boston, MA USA. [Zanni, Markella V.; Fitch, Kathleen; Stavrou, Eleni; Grinspoon, Steven] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Zanni, Markella V.; Fitch, Kathleen; Stavrou, Eleni; Grinspoon, Steven] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Lim, Ruth] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Cypess, Aaron M.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU National Institutes of Health [1UL1RR025758, 2P30AI060354, F32 DK085969, K23 DK081604, K24 DK064545, M01-RR-01066, 1 UL1 RR025758-01]; National Center for Research Resources; NIH [P30DK040561] FX This work was supported by National Institutes of Health Grants 1UL1RR025758 and 2P30AI060354 to MT, F32 DK085969 to MVZ, K23 DK081604 to AMC, K24 DK064545 to SG and M01-RR-01066 and 1 UL1 RR025758-01 supporting Harvard Clinical and Translational Science Center, from the National Center for Research Resources. This work was also supported in part by the NIH grant P30DK040561 to the Nutrition Obesity Research Center at Harvard. The Clinical Trial Registration number is NCT01098045. NR 20 TC 7 Z9 7 U1 0 U2 2 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 2013 VL 18 IS 2 BP 243 EP 248 DI 10.3851/IMP2420 PG 6 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 290LP UT WOS:000329759300013 PM 23041595 ER PT J AU Schackman, BR Haas, DW Becker, JE Berkowitz, BK Sax, PE Daar, ES Ribaudo, HJ Freedberg, KA AF Schackman, Bruce R. Haas, David W. Becker, Jessica E. Berkowitz, Bethany K. Sax, Paul E. Daar, Eric S. Ribaudo, Heather J. Freedberg, Kenneth A. TI Cost-effectiveness analysis of UGT1A1 genetic testing to inform antiretroviral prescribing in HIV disease SO ANTIVIRAL THERAPY LA English DT Article ID DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A1; ATAZANAVIR PLUS RITONAVIR; UNITED-STATES; OPPORTUNISTIC INFECTIONS; GILBERTS-SYNDROME; THERAPY; CARE; PHARMACOGENOMICS; ASSOCIATION; PREVENTION AB Background: Homozygosity for UGT1A1*28/* 28 has been reported to be associated with atazanavir-associated hyperbilirubinaemia and premature atazanavir discontinuation. We assessed the potential cost-effectiveness of UGT1A1 testing to inform the choice of an initial protease-inhibitor-containing regimen in antiretroviral therapy (ART)-naive individuals. Methods: We used the Cost-Effectiveness of Preventing AIDS Complications computer simulation model to project quality-adjusted life years (QALYs) and lifetime costs (2009 USD) for atazanavir-based ART with or without UGT1A1 testing, using darunavir rather than atazanavir when indicated. We assumed the UGT1A1-associated atazanavir discontinuation rate reported in the Swiss HIV Cohort Study (a *28/* 28 frequency of 14.9%), equal efficacy and cost of atazanavir and darunavir and a genetic assay cost of $ 107. These parameters, as well as the effect of hyperbilirubinaemia on quality of life and loss to follow up, were varied in sensitivity analyses. Costs and QALYs were discounted at 3% annually. Results: Initiating atazanavir-based ART at CD4+ T-cell counts < 500 cells/l without UGT1A1 testing had an average discounted life expectancy of 16.02 QALYs and $ 475,800 discounted lifetime cost. Testing for UGT1A1 increased QALYs by 0.49 per 10,000 patients tested and was not cost-effective (>$ 100,000/QALY). Testing for UGT1A1 was cost-effective (<$ 100,000/QALY) if assay cost decreased to $ 10, or if avoiding hyperbilirubinaemia by UGT1A1 testing reduced loss to follow-up by 5%. If atazanavir and darunavir differed in cost or efficacy, testing for UGT1A1 was not cost-effective under any scenario. Conclusions: Testing for UGT1A1 may be cost-effective if assay cost is low and if testing improves retention in care, but only if the comparator ART regimens have the same drug cost and efficacy. C1 [Schackman, Bruce R.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY 10021 USA. [Haas, David W.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. [Haas, David W.] Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37212 USA. [Haas, David W.] Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37212 USA. [Haas, David W.] Vanderbilt Univ, Sch Med, Dept Microbiol, Nashville, TN 37212 USA. [Haas, David W.] Vanderbilt Univ, Sch Med, Dept Immunol, Div Infect Dis, Nashville, TN 37212 USA. [Haas, David W.] Vanderbilt Univ, Sch Med, Dept Immunol, Div Clin Pharmacol, Nashville, TN 37212 USA. [Becker, Jessica E.; Berkowitz, Bethany K.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Div Gen Med, Boston, MA 02114 USA. [Sax, Paul E.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Div Aids, Boston, MA USA. [Sax, Paul E.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. [Sax, Paul E.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Daar, Eric S.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Div HIV Med, Torrance, CA 90509 USA. [Ribaudo, Heather J.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Ribaudo, Heather J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Schackman, BR (reprint author), Weill Cornell Med Coll, Dept Publ Hlth, New York, NY 10021 USA. EM brs2006@med.cornell.edu FU National Institute of Allergy and Infectious Diseases [R37 AI42006, R01 AI077505, AI069439, AI054999, A1069424]; National Center for Advancing Translational Sciences [TR000011] FX We acknowledge Jared Leff for assistance in conducting the probabilistic sensitivity analyses and Julia Maxwell for assistance in project management. This study was funded by the National Institute of Allergy and Infectious Diseases R37 AI42006 (BRS, JEB, BKB, KAF, PES), R01 AI077505 (BRS, DWH, JEB, BKB, KAF, HJR), AI069439 (DWH), AI054999 (DWH) and A1069424 (ESD) and the National Center for Advancing Translational Sciences TR000011 (DWH). This study was presented in part at the 19th Conference on Retroviruses and Opportunistic Infections (5-8 March 2012, Seattle, WA, USA Abstract 598), and at the 34th Annual Meeting of the Society for Medical Decision Making (17-20 October 2012. Phoenix, AZ, USA Abstract K-5). NR 41 TC 7 Z9 7 U1 0 U2 1 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 2013 VL 18 IS 3 BP 399 EP 408 DI 10.3851/IMP2500 PG 10 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 290LT UT WOS:000329760000015 PM 23264445 ER PT J AU Borand, L Laureillard, D Madec, Y Chou, M Pheng, P Marcy, O Sok, T Goldfeld, AE Taburet, AM Blanc, FX AF Borand, Laurence Laureillard, Didier Madec, Yoann Chou, Monidarin Pheng, Phearavin Marcy, Olivier Sok, Thim Goldfeld, Anne E. Taburet, Anne-Marie Blanc, Francois-Xavier CA CAMELIA ANRS 1295-CIPRA KH001 Stud TI Plasma concentrations of efavirenz with a 600 mg standard dose in Cambodian HIV-infected adults treated for tuberculosis with a body weight above 50 kg SO ANTIVIRAL THERAPY LA English DT Article ID PHARMACOKINETIC INTERACTIONS; ANTIRETROVIRAL TREATMENT; RIFAMPICIN; THERAPY; MG/DAY AB Background: The optimal dose of efavirenz for HIV-infected patients receiving a tuberculosis regimen including rifampicin remains debated, especially for subjects weighing over 50 kg. To address this issue, we measured plasma efavirenz concentrations from Cambodian adults with tuberculosis enrolled in the CAMELIA randomized trial (ClinicalTrials.gov number, NCT01300481) 6 weeks after the onset of antiretroviral therapy. Methods: Efavirenz concentrations and proportions of patients with concentrations below 1,000 ng/ml were compared across patient body weight below or above 50 kg using a Student's t-test and a chi(2) test, respectively. Factors associated with efavirenz concentrations below 1,000 ng/ml were identified by logistic regression analysis. Logistic regression analysis was also performed to check if efavirenz concentrations below 1,000 ng/ml were associated with virological failure. Results: Plasma efavirenz concentrations were higher in the 332 patients who weighed <50 kg compared with the 150 who weighed >= 50 kg (median [IQR] 2,859 [1,787-4,749] and 2,060 [1,425-3,575] ng/ml, respectively; P=0.02). However, the proportion of patients with efavirenz concentrations below 1,000 ng/ml was not different between those weighing less than or more than 50 kg (6% and 10%, respectively; P=0.13) and a body weight above 50 kg was not associated with a higher risk of plasma efavirenz concentrations below 1,000 ng/ml. When plasma efavirenz concentrations below 1,000 ng/ml were present, they were not associated with virological failure. Conclusions: The current WHO guidelines recommending 600 mg efavirenz daily irrespective of patient's body weight remains a safe and effective approach to treating coinfected adults needing simultaneous tuberculosis and HIV therapy. C1 [Borand, Laurence; Pheng, Phearavin; Marcy, Olivier] Inst Pasteur Cambodge, Epidemiol & Publ Hlth Unit, Phnom Penh, Cambodia. [Laureillard, Didier] ANRS, Ho Chi Minh City, Vietnam. [Madec, Yoann] Inst Pasteur, Unite Rech & Expertise Epidemiol Malad Emergentes, Paris, France. [Chou, Monidarin] Univ Hlth Sci, Fac Pharm, Phnom Penh, Cambodia. [Sok, Thim; Goldfeld, Anne E.] Cambodian Hlth Comm, Phnom Penh, Cambodia. [Goldfeld, Anne E.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. [Taburet, Anne-Marie] Hop Univ Paris Sud, Hop Bicetre, AP HP, Dept Clin Pharm, Le Kremlin Bicetre, France. [Blanc, Francois-Xavier] Hop Univ Paris Sud, Hop Bicetre, AP HP, Dept Pneumol, Le Kremlin Bicetre, France. RP Blanc, FX (reprint author), Hop Univ Paris Sud, Hop Bicetre, AP HP, Dept Pneumol, Le Kremlin Bicetre, France. EM xavier.blanc@bct.aphp.fr RI Blanc, Francois-Xavier/D-7425-2015 FU French National Agency for Research on AIDS and Viral Hepatitis (ANRS); ANRS [1295, CIPRA KH001] FX The authors are grateful to the patients who accepted to participate to this study and to the patients' representatives who contributed to the information sheet and consent form writing. They are grateful to the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) and the US National Institutes of Health Division of AIDS who both funded the CAMELIA clinical trial and to the Rodolphe Merieux Foundation for the collaboration on the pharmacokinetics assays. The authors would also like to acknowledge the CAMELIA teams from the study sites, Cambodian Health Committee, Institut Pasteur du Cambodge, and Medecins Sans Frontieres Belgium for their active contribution to the trial. This work was supported by the ANRS (study number 1295) and the US National Institutes of Health Division of AIDS (CIPRA KH001). NR 20 TC 6 Z9 6 U1 0 U2 2 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 2013 VL 18 IS 3 BP 419 EP 423 DI 10.3851/IMP2483 PG 5 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 290LT UT WOS:000329760000017 PM 23237982 ER PT J AU Arvikar, SL Collier, DS Fisher, MC Unizony, S Cohen, GL McHugh, G Kawai, T Strle, K Steere, AC AF Arvikar, Sheila L. Collier, Deborah S. Fisher, Mark C. Unizony, Sebastian Cohen, George L. McHugh, Gail Kawai, Toshihisa Strle, Klemen Steere, Allen C. TI Clinical correlations with Porphyromonas gingivalis antibody responses in patients with early rheumatoid arthritis SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID PERIODONTAL-DISEASE; ALPHA-ENOLASE; ASSOCIATION; AUTOIMMUNITY; AUTOANTIBODIES; POPULATION; SEVERITY; IMMUNITY; ADULTS AB Introduction: Prior studies have demonstrated an increased frequency of antibodies to Porphyromonas gingivalis (Pg), a leading agent of periodontal disease, in rheumatoid arthritis (RA) patients. However, these patients generally had long-standing disease, and clinical associations with these antibodies were inconsistent. Our goal was to examine Pg antibody responses and their clinical associations in patients with early RA prior to and after disease-modifying antirheumatic drug (DMARD) therapy. Methods: Serum samples from 50 DMARD-nave RA patients were tested using an enzyme-linked immunosorbent assay with whole-Pg sonicate. For comparison, serum samples were tested from patients with late RA, patients with other connective tissue diseases (CTDs), age-similar healthy hospital personnel and blood bank donors. Pg antibody responses in early RA patients were correlated with standard RA biomarkers, measures of disease activity and function. Results: At the time of enrollment, 17 (34%) of the 50 patients with early RA had positive immunoglobulin G (IgG) antibody responses to Pg, as did 13 (30%) of the 43 patients with late RA. RA patients had significantly higher Pg antibody responses than healthy hospital personnel and blood bank donors (P < 0.0001). Additionally, RA patients tended to have higher Pg antibody reactivity than patients with other CTDs (P = 0.1), and CTD patients tended to have higher Pg responses than healthy participants (P = 0.07). Compared with Pg antibody-negative patients, early RA patients with positive Pg responses more often had anti-cyclic citrullinated peptide (anti-CCP) antibody reactivity, their anti-CCP levels were significantly higher (P = 0.03) and the levels of anti-Pg antibodies correlated directly with anti-CCP levels (P < 0.01). Furthermore, at the time of study entry, the Pg-positive antibody group had greater rheumatoid factor values (P = 0.04) and higher inflammatory markers (erythrocyte sedimentation rate, or ESR) (P = 0.05), and they tended to have higher disease activity scores (Disease Activity Score based on 28-joint count (DAS28)-ESR and Clinical Disease Activity Index) and more functional impairment (Health Assessment Questionnaire). In Pg-positive patients, greater disease activity was still apparent after 12 months of DMARD therapy. Conclusions: A subset of early RA patients had positive Pg antibody responses. The responses correlated with anti-CCP antibody reactivity and to a lesser degree with ESR values. There was a trend toward greater disease activity in Pg-positive patients, and this trend remained after 12 months of DMARD therapy. These findings are consistent with a role for Pg in disease pathogenesis in a subset of RA patients. C1 [Arvikar, Sheila L.; Collier, Deborah S.; Fisher, Mark C.; Unizony, Sebastian; Cohen, George L.; McHugh, Gail; Strle, Klemen; Steere, Allen C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Ctr Immunol & Inf, Charlestown, MA 02129 USA. [Kawai, Toshihisa] Forsyth Inst, Cambridge, MA 02142 USA. [Arvikar, Sheila L.] Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. RP Arvikar, SL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Ctr Immunol & Inf, 149 13th St, Charlestown, MA 02129 USA. EM sarvikar@partners.org FU American College of Rheumatology; Dana Foundation; English Bonter Mitchell Foundation; Mathers Foundation; Ounsworth-Fitzgerald Foundation; Nathan Littauer Foundation; Lyme/Arthritis Research Fund at MGH; Eshe Fund; National Institutes of Health (NIH) [CA069212]; NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases) [AR-007258]; Arthritis Foundation FX This study was supported in part by the American College of Rheumatology grant program "Within our Reach: Finding a Cure for Rheumatoid Arthritis"; the Dana Foundation; the English Bonter Mitchell Foundation; the Mathers Foundation; the Ounsworth-Fitzgerald Foundation; the Nathan Littauer Foundation; the Lyme/Arthritis Research Fund at MGH; the Eshe Fund; and the National Institutes of Health (NIH) (grant CA069212). SLA was supported by an NIH training grant (National Institute of Arthritis and Musculoskeletal and Skin Diseases grant AR-007258) and a postdoctoral fellowship award from the Arthritis Foundation. The authors thank Dr Mandakolathur Murali, director of the MGH Clinical Immunology Laboratory, for assistance in obtaining patient serum samples and performing anti-CCP antibody testing and Colin Gorman, the study coordinator, for help with administrative aspects of the study. NR 38 TC 14 Z9 15 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2013 VL 15 IS 5 AR R109 DI 10.1186/ar4289 PG 12 WC Rheumatology SC Rheumatology GA 290ET UT WOS:000329737400009 PM 24017968 ER PT J AU Hamblin, MR AF Hamblin, Michael R. TI Can osteoarthritis be treated with light? SO ARTHRITIS RESEARCH & THERAPY LA English DT Editorial Material ID LEVEL LASER THERAPY AB Osteoarthritis is becoming more problematic as the population ages. Recent reports suggest that the benefit of anti-inflammatory drugs is unimpressive and the incidence of side effects is worrying. Low-level laser (light) therapy (LLLT) is an alternative approach with no known side effects and with reports of substantial therapeutic efficacy in osteoarthritis. In this issue of Arthritis Research & Therapy, Alves and colleagues used a rat model of osteoarthritis produced by intra-articular injection of the cartilage-degrading enzyme papain to test 810-nm LLLT. A single application of LLLT produced significant reductions in inflammatory cell infiltration and inflammatory cytokines 24 hours later. A lower laser power was more effective than a higher laser power. However, more work is necessary before the title question can be answered in the affirmative. C1 [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR414,40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU NIAID NIH HHS [R01AI050875] NR 11 TC 3 Z9 3 U1 2 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2013 VL 15 IS 5 AR 120 DI 10.1186/ar4354 PG 2 WC Rheumatology SC Rheumatology GA 290ET UT WOS:000329737400077 PM 24286607 ER PT B AU Prabhala, HK Pai, C Prabhala, RH AF Prabhala, H. K. Pai, C. Prabhala, R. H. BE Watson, RR Preedy, VR TI Anti-Inflammatory Natural Foods SO BIOACTIVE FOOD AS DIETARY INTERVENTIONS FOR ARTHRITIS AND RELATED INFLAMMATORY DISEASES SE Bioactive Foods in Chronic Disease States LA English DT Article; Book Chapter ID PRODUCTS C1 [Prabhala, H. K.] Univ Virginia, Charlottesville, VA 22903 USA. [Pai, C.; Prabhala, R. H.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. [Prabhala, R. H.] Brigham & Womans Hosp, Boston, MA USA. [Prabhala, R. H.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Prabhala, HK (reprint author), Univ Virginia, Charlottesville, VA 22903 USA. NR 20 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-397765-6; 978-0-12-397156-2 J9 BIOACT FOOD CHRON PY 2013 BP 279 EP 303 DI 10.1016/B978-0-12-397156-2.00020-X PG 25 WC Nutrition & Dietetics; Rheumatology SC Nutrition & Dietetics; Rheumatology GA BJM07 UT WOS:000329031700022 ER PT J AU Patel, RB Stoklosa, H Shitole, S Shitole, T Sawant, K Nanarkar, M Subbaraman, R Ridpath, A Patil-Deshmuk, A AF Patel, Ronak B. Stoklosa, Hanni Shitole, Shrutika Shitole, Tejal Sawant, Kiran Nanarkar, Mahesh Subbaraman, Ramnath Ridpath, Alison Patil-Deshmuk, Anita TI The high cost of diarrhoeal illness for urban slum households-a cost-recovery approach: a cohort study SO BMJ OPEN LA English DT Article DE Urbanisation; Preventive medicine; Poverty; Diarrhoea ID HEALTH; SANITATION; CHILDREN; INDIA; WATER; CITY AB Objectives Rapid urbanisation has often meant that public infrastructure has not kept pace with growth leading to urban slums with poor access to water and sanitation and high rates of diarrhoea with greater household costs due to illness. This study sought to determine the monetary cost of diarrhoea to urban slum households in Kaula Bandar slum in Mumbai, India. The study also tested the hypotheses that the cost of water and sanitation infrastructure may be surpassed by the cumulative costs of diarrhoea for households in an urban slum community. Design A cohort study using a baseline survey of a random sample followed by a systematic longitudinal household survey. The baseline survey was administered to a random sample of households. The systematic longitudinal survey was administered to every available household in the community with a case of diarrhoea for a period of 5weeks. Participants Every household in Kaula Bandar was approached for the longitudinal survey and all available and consenting adults were included. Results The direct cost of medical care for having at least one person in the household with diarrhoea was 205 rupees. Other direct costs brought total expenses to 291 rupees. Adding an average loss of 55 rupees per household from lost wages and monetising lost productivity from homemakers gave a total loss of 409 rupees per household. During the 5-week study period, this community lost an estimated 163600 rupees or 3635 US dollars due to diarrhoeal illness. Conclusions The lack of basic water and sanitation infrastructure is expensive for urban slum households in this community. Financing approaches that transfer that cost to infrastructure development to prevent illness may be feasible. These findings along with the myriad of unmeasured benefits of preventing diarrhoeal illness add to pressing arguments for investment in basic water and sanitation infrastructure. C1 [Patel, Ronak B.; Stoklosa, Hanni] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Patel, Ronak B.; Stoklosa, Hanni] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Patel, Ronak B.; Ridpath, Alison] Harvard Humanitarian Initiat, Cambridge, MA USA. [Shitole, Shrutika; Shitole, Tejal; Sawant, Kiran; Nanarkar, Mahesh; Subbaraman, Ramnath; Patil-Deshmuk, Anita] Partners Urban Knowledge Act & Res, Mumbai, Maharashtra, India. RP Patel, RB (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. EM rbpatel1@partners.org FU Rockefeller Foundation FX Rockefeller Foundation provided financial support. NR 24 TC 2 Z9 2 U1 0 U2 4 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 2013 VL 3 IS 4 AR e002251 DI 10.1136/bmjopen-2012-002251 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 291DZ UT WOS:000329809200010 ER PT J AU Singh, JA Hawn, M Campagna, EJ Henderson, WG Richman, J Houston, TK AF Singh, Jasvinder A. Hawn, Mary Campagna, Elizabeth J. Henderson, William G. Richman, Joshua Houston, Thomas K. TI Mediation of smoking-associated postoperative mortality by perioperative complications in veterans undergoing elective surgery: data from Veterans Affairs Surgical Quality Improvement Program (VASQIP)-a cohort study SO BMJ OPEN LA English DT Article DE Epidemiology ID CARDIAC RISK-ASSESSMENT; PULMONARY COMPLICATIONS; NONCARDIAC SURGERY; QUIT RATES; CESSATION PROGRAM; ABDOMINAL-SURGERY; EUROPEAN-SOCIETY; UNITED-STATES; GUIDELINES; PREVALENCE AB Objective To assess the mediation of smoking-associated postoperative mortality by postoperative complications. Design Observational cohort study. Setting Using data from the Veterans Affairs (VA) Surgical Quality Improvement Programme, a quality assurance programme for major surgical procedures in the VA healthcare system, we assessed the association of current smoking at the time of the surgery with 6-month and 1-year mortality. Primary and secondary outcome measures Using mediation analyses, we calculated the relative contribution of each smoking-associated complication to smoking-associated postoperative mortality, both unadjusted and adjusted for age, race/ethnicity, work relative value unit of the operation, surgeon specialty, American Society of Anesthesiologists class and year of surgery. Smoking-associated complications included surgical site infection (SSI), cardiovascular complications (myocardial infarction, cardiac arrest and/or stroke) and pulmonary complications (pneumonia, failure to wean and/or reintubation). Results There were 186632 never smokers and 135741 current smokers. The association of smoking and mortality was mediated by smoking-related complications with varying effects. In unadjusted analyses, the proportions of mediation of smoking to 6-month mortality explained by the complications were as follows: SSIs 22%, cardiovascular complications 12% and pulmonary complications 89%. In adjusted analyses, the per cents mediated by each complication were as follows: SSIs 2%, cardiovascular complications 4% and pulmonary complications 22%. In adjusted analyses for 1-year mortality, respective per cents mediated were 2%, 3% and 16%. Conclusions Pulmonary complications, followed by cardiovascular complications and SSIs were mediators of smoking-associated 6-month and 1-year mortality. Interventions targeting smoking cessation and prevention and early treatment of pulmonary complications has the likelihood of reducing postoperative mortality after elective surgery. C1 [Singh, Jasvinder A.; Hawn, Mary; Richman, Joshua] Univ Alabama Birmingham, Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Hawn, Mary; Richman, Joshua] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.; Hawn, Mary] Birmingham VA Med Ctr, Ctr Surg Med Acute Care Res & Transit, Birmingham, AL USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. [Campagna, Elizabeth J.; Henderson, William G.] Univ Colorado Denver, Colorado Hlth Outcomes Program, Aurora, CO USA. [Campagna, Elizabeth J.] VA Med Ctr, Denver, CO USA. [Houston, Thomas K.] Bedford VA Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. [Houston, Thomas K.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Birmingham VA Med Ctr, Med Serv, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com OI singh, jasvinder/0000-0003-3485-0006 FU Veterans Affairs Research Grant [VA IIR IAB 06-038-2] FX Veterans Affairs Research Grant - VA IIR IAB 06-038-2. NR 37 TC 4 Z9 4 U1 0 U2 1 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 2013 VL 3 IS 4 AR e002157 DI 10.1136/bmjopen-2012-002157 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 291DZ UT WOS:000329809200016 ER PT J AU Deng, J Letai, A AF Deng, Jing Letai, Anthony TI Priming BCL-2 to kill: the combination therapy of tamoxifen and ABT-199 in ER+ breast cancer SO BREAST CANCER RESEARCH LA English DT Article ID ANTITUMOR-ACTIVITY; INHIBITOR; RESISTANCE; NAVITOCLAX; ABT-737; POTENT; TUMORS AB The B-cell lymphoma/leukemia 2 protein (BCL-2) may help many types of cancers to evade cell death. However, identifying exactly where this is the case is a challenge. ABT-199 is a small molecule that selectively inhibits BCL-2, which is currently in clinical trials in lymphoid malignancies. While inhibiting BCL-2 by itself can cause cell death in hematopoietic tumors, single-agent activity is harder to observe in solid tumors. Combining ABT-199 with tamoxifen, the standard endocrine therapy for estrogen receptor-positive breast cancers, 85% of which have BCL-2 expression, represents a new strategy to prime cancer cells for apoptosis and elicit better cancer cell death responses. C1 [Deng, Jing; Letai, Anthony] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Letai, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM anthony_letai@dfci.harvard.edu NR 15 TC 4 Z9 4 U1 1 U2 4 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. PY 2013 VL 15 IS 5 AR 317 DI 10.1186/bcr3568 PG 2 WC Oncology SC Oncology GA 290NA UT WOS:000329763800040 PM 24172207 ER PT J AU Karlsson, E Perez-Tenorio, G Amin, R Bostner, J Skoog, L Fornander, T Sgroi, DC Nordenskjold, B Hallbeck, AL Stal, O AF Karlsson, Elin Perez-Tenorio, Gizeh Amin, Risul Bostner, Josefine Skoog, Lambert Fornander, Tommy Sgroi, Dennis C. Nordenskjold, Bo Hallbeck, Anna-Lotta Stal, Olle TI The mTOR effectors 4EBP1 and S6K2 are frequently coexpressed, and associated with a poor prognosis and endocrine resistance in breast cancer: a retrospective study including patients from the randomised Stockholm tamoxifen trials SO BREAST CANCER RESEARCH LA English DT Article ID TERM-FOLLOW-UP; POSTMENOPAUSAL BREAST; MAMMALIAN TARGET; IMMUNOHISTOCHEMICAL ANALYSIS; ADJUVANT CHEMOTHERAPY; 4E-BINDING PROTEIN-1; EXPRESSION SIGNATURE; C-ERBB-2 EXPRESSION; CELL-PROLIFERATION; RAPAMYCIN MTOR AB Introduction: mTOR and its downstream effectors the 4E-binding protein 1 (4EBP1) and the p70 ribosomal S6 kinases (S6K1 and S6K2) are frequently upregulated in breast cancer, and assumed to be driving forces in tumourigenesis, in close connection with oestrogen receptor (ER) networks. Here, we investigated these factors as clinical markers in five different cohorts of breast cancer patients. Methods: The prognostic significance of 4EBP1, S6K1 and S6K2 mRNA expression was assessed with real-time PCR in 93 tumours from the treatment randomised Stockholm trials, encompassing postmenopausal patients enrolled between 1976 and 1990. Three publicly available breast cancer cohorts were used to confirm the results. Furthermore, the predictive values of 4EBP1 and p4EBP1_S65 protein expression for both prognosis and endocrine treatment benefit were assessed by immunohistochemical analysis of 912 node-negative breast cancers from the Stockholm trials. Results: S6K2 and 4EBP1 mRNA expression levels showed significant correlation and were associated with a poor outcome in all cohorts investigated. 4EBP1 protein was confirmed as an independent prognostic factor, especially in progesterone receptor (PgR)-expressing cancers. 4EBP1 protein expression was also associated with a poor response to endocrine treatment in the ER/PgR positive group. Cross-talk to genomic as well as non-genomic ER/PgR signalling may be involved and the results further support a combination of ER and mTOR signalling targeted therapies. Conclusion: This study suggests S6K2 and 4EBP1 as important factors for breast tumourigenesis, interplaying with hormone receptor signalling. We propose S6K2 and 4EBP1 as new potential clinical markers for prognosis and endocrine therapy response in breast cancer. C1 [Karlsson, Elin; Perez-Tenorio, Gizeh; Amin, Risul; Bostner, Josefine; Nordenskjold, Bo; Hallbeck, Anna-Lotta; Stal, Olle] Linkoping Univ, Div Oncol, Dept Clin & Expt Med, Cty Council Ostergotland, SE-58185 Linkoping, Sweden. [Skoog, Lambert] Karolinska Univ Hosp, Dept Pathol & Cytol, SE-17176 Stockholm, Sweden. [Fornander, Tommy] Stockholm South Gen Hosp, Karolinska Univ Hosp, Dept Oncol, SE-11883 Stockholm, Sweden. [Sgroi, Dennis C.] Massachusetts Gen Hosp, Mol Pathol Res Unit, Dept Pathol, Boston, MA 02129 USA. RP Karlsson, E (reprint author), Linkoping Univ, Div Oncol, Dept Clin & Expt Med, Cty Council Ostergotland, SE-58185 Linkoping, Sweden. EM elin.karlsson@liu.se NR 48 TC 21 Z9 21 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. PY 2013 VL 15 IS 5 AR R96 DI 10.1186/bcr3557 PG 14 WC Oncology SC Oncology GA 290NA UT WOS:000329763800024 PM 24131622 ER PT J AU Rentz, DM Rodriguez, MAP Amariglio, R Stern, Y Sperling, R Ferris, S AF Rentz, Dorene M. Rodriguez, Mario A. Parra Amariglio, Rebecca Stern, Yaakov Sperling, Reisa Ferris, Steven TI Promising developments in neuropsychological approaches for the detection of preclinical Alzheimer's disease: a selective review SO ALZHEIMERS RESEARCH & THERAPY LA English DT Review ID MILD COGNITIVE IMPAIRMENT; PITTSBURGH-COMPOUND-B; SHORT-TERM-MEMORY; POSITRON-EMISSION-TOMOGRAPHY; NORMAL OLDER INDIVIDUALS; AMYLOID DEPOSITION; EPISODIC MEMORY; WORKING-MEMORY; ENTORHINAL CORTEX; HIPPOCAMPAL ACTIVATION AB Recently published guidelines suggest that the most opportune time to treat individuals with Alzheimer's disease is during the preclinical phase of the disease. This is a phase when individuals are defined as clinically normal but exhibit evidence of amyloidosis, neurodegeneration and subtle cognitive/behavioral decline. While our standard cognitive tests are useful for detecting cognitive decline at the stage of mild cognitive impairment, they were not designed for detecting the subtle cognitive variations associated with this biomarker stage of preclinical Alzheimer's disease. However, neuropsychologists are attempting to meet this challenge by designing newer cognitive measures and questionnaires derived from translational efforts in neuroimaging, cognitive neuroscience and clinical/experimental neuropsychology. This review is a selective summary of several novel, potentially promising, approaches that are being explored for detecting early cognitive evidence of preclinical Alzheimer's disease in presymptomatic individuals. C1 [Rentz, Dorene M.; Amariglio, Rebecca; Sperling, Reisa] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Alzheimer Res & Treatment,Dept Neurol, Boston, MA 02115 USA. [Rentz, Dorene M.; Amariglio, Rebecca; Sperling, Reisa] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. [Rodriguez, Mario A. Parra] Univ Edinburgh, Dept Psychol, Ctr Cognit Aging & Cognit Epidemiol, Alzheimer Scotland Dementia Res Ctr, Edinburgh EH8 9JZ, Midlothian, Scotland. [Rodriguez, Mario A. Parra] Scottish Dementia Clin Res Network, Edinburgh EH8 9JZ, Midlothian, Scotland. [Stern, Yaakov] Columbia Univ Coll Phys & Surg, Dept Neurol, Taub Inst Res Alzheimers Dis & Aging Brain, Cognit Neurosci Div, New York, NY 10032 USA. [Ferris, Steven] NYU, Langone Med Ctr, Dept Psychiat, Alzheimers Dis Ctr,Comprehens Ctr Brain Aging, New York, NY 10016 USA. RP Rentz, DM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Alzheimer Res & Treatment,Dept Neurol, 221 Longwood Ave, Boston, MA 02115 USA. EM drentz@partners.org OI Ferris, Steven/0000-0001-8641-6223 FU Fellow of Alzheimer's Society, UK [RF165] FX The authors wish to thank all of the subjects who make research possible. MAPR is currently a Fellow of Alzheimer's Society, UK, Project Grant Number RF165. NR 95 TC 30 Z9 30 U1 5 U2 20 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-9193 J9 ALZHEIMERS RES THER JI Alzheimers Res. Ther. PY 2013 VL 5 IS 6 AR 58 DI 10.1186/alzrt222 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 292NQ UT WOS:000329909300006 PM 24257331 ER PT J AU Shah, RC Kamphuis, PJ Leurgans, S Swinkels, SH Sadowsky, CH Bongers, A Rappaport, SA Quinn, JF Wieggers, RL Scheltens, P Bennett, DA AF Shah, Raj C. Kamphuis, Patrick J. Leurgans, Sue Swinkels, Sophie H. Sadowsky, Carl H. Bongers, Anke Rappaport, Stephen A. Quinn, Joseph F. Wieggers, Rico L. Scheltens, Philip Bennett, David A. TI The S-Connect study: results from a randomized, controlled trial of Souvenaid in mild-to-moderate Alzheimer's disease SO ALZHEIMERS RESEARCH & THERAPY LA English DT Article ID DEMENTIA RATING CDR; NATIONAL INSTITUTE; CLINICAL-TRIALS; NORMATIVE DATA; MEDICAL FOOD; SYNAPSE LOSS; EFFICACY; GUIDELINES; BRAIN; SCALE AB Introduction: Souvenaid r containing Fortasyn r Connect is a medical food designed to support synapse synthesis in persons with Alzheimer's disease (AD). Fortasyn Connect includes precursors (uridine monophosphate; choline; phospholipids; eicosapentaenoic acid; docosahexaenoic acid) and cofactors (vitamins E, C, B12, and B6; folic acid; selenium) for the formation of neuronal membranes. Whether Souvenaid slows cognitive decline in treated persons with mild-to-moderate AD has not been addressed. Methods: In a 24-week, double-masked clinical trial at 48 clinical centers, 527 participants taking AD medications [52% women, mean age 76.7 years (Standard Deviation, SD = 8.2), and mean Mini-Mental State Examination score 19.5 (SD = 3.1, range 14-24)] were randomized 1: 1 to daily, 125-mL (125 kcal), oral intake of the active product (Souvenaid) or an iso-caloric control. The primary outcome of cognition was assessed by the 11-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog). Compliance was calculated from daily diary recordings of product intake. Statistical analyses were performed using mixed models for repeated measures. Results: Cognitive performance as assessed by ADAS-cog showed decline over time in both control and active study groups, with no significant difference between study groups (difference = 0.37 points, Standard Error, SE = 0.57, p = 0.513). No group differences in adverse event rates were found and no clinically relevant differences in blood safety parameters were noted. Overall compliance was high (94.1% [active] and 94.5% [control]), which was confirmed by significant changes in blood (nutritional) biomarkers. Conclusions: Add-on intake of Souvenaid during 24 weeks did not slow cognitive decline in persons treated for mild-to-moderate AD. Souvenaid was well tolerated in combination with standard care AD medications. C1 [Shah, Raj C.; Leurgans, Sue; Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Kamphuis, Patrick J.; Swinkels, Sophie H.; Bongers, Anke; Wieggers, Rico L.] Nutricia Res, Nutricia Adv Med Nutr, NL-3584 TC Utrecht, Netherlands. [Swinkels, Sophie H.] Nutricia Res, NL-3584 TC Utrecht, Netherlands. [Sadowsky, Carl H.] Nova SE Univ, Dept Neurol, W Palm Beach, FL USA. [Rappaport, Stephen A.] Agewell Hlth, Indianapolis, IN USA. [Quinn, Joseph F.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Quinn, Joseph F.] Portland VA Med Ctr, Portland, OR 97201 USA. [Scheltens, Philip] Vrije Univ Amsterdam Med Ctr, Alzheimer Ctr, NL-1007 MB Amsterdam, Netherlands. RP Shah, RC (reprint author), Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, 600 South Paulina,Suite 1022, Chicago, IL 60612 USA. EM Raj_C_Shah@rush.edu NR 29 TC 23 Z9 23 U1 3 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-9193 J9 ALZHEIMERS RES THER JI Alzheimers Res. Ther. PY 2013 VL 5 IS 6 AR 59 DI 10.1186/alzrt224 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 292NQ UT WOS:000329909300007 PM 24280255 ER PT S AU Petschow, B Dore, J Hibberd, P Dinan, T Reid, G Blaser, M Cani, PD Degnan, FH Foster, J Gibson, G Hutton, J Klaenhammer, TR Ley, R Nieuwdorp, M Pot, B Relman, D Serazin, A Sanders, ME AF Petschow, Bryon Dore, Joel Hibberd, Patricia Dinan, Timothy Reid, Gregor Blaser, Martin Cani, Patrice D. Degnan, Fred H. Foster, Jane Gibson, Glenn Hutton, John Klaenhammer, Todd R. Ley, Ruth Nieuwdorp, Max Pot, Bruno Relman, David Serazin, Andrew Sanders, Mary Ellen GP NYAS TI Probiotics, prebiotics, and the host microbiome: the science of translation SO ANNALS REPORTS SE Annals of the New York Academy of Sciences LA English DT Article DE microbiome; probiotics; prebiotics; intestinal microbiota; health disorders ID DIET-INDUCED OBESITY; IRRITABLE-BOWEL-SYNDROME; GERM-FREE MICE; GUT MICROBIOTA; INTESTINAL MICROBIOTA; INSULIN-RESISTANCE; INFLAMMATION; SYSTEM; INFANT; COLONIZATION AB Recent advances in our understanding of the community structure and function of the human microbiome have implications for the potential role of probiotics and prebiotics in promoting human health. A group of experts recently met to review the latest advances in microbiota/microbiome research and discuss the implications for development of probiotics and prebiotics, primarily as they relate to effects mediated via the intestine. The goals of the meeting were to share recent advances in research on the microbiota, microbiome, probiotics, and prebiotics, and to discuss these findings in the contexts of regulatory barriers, evolving healthcare environments, and potential effects on a variety of health topics, including the development of obesity and diabetes; the long-term consequences of exposure to antibiotics early in life to the gastrointestinal (GI) microbiota; lactose intolerance; and the relationship between the GI microbiota and the central nervous system, with implications for depression, cognition, satiety, and mental health for people living in developed and developing countries. This report provides an overview of these discussions. C1 [Petschow, Bryon] Transcend Biomed Commun LLC, Youngsville, NC USA. [Dore, Joel] INRA, Paris, France. [Hibberd, Patricia] Harvard Univ, Sch Med, Boston, MA USA. [Hibberd, Patricia] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dinan, Timothy] Natl Univ Ireland Univ Coll Cork, Cork, Ireland. [Reid, Gregor] Univ Western Ontario, London, ON, Canada. [Reid, Gregor] Lawson Hlth Res Inst, London, ON, Canada. [Blaser, Martin] NYU, Sch Med, New York, NY USA. [Cani, Patrice D.] Catholic Univ Louvain, Louvain Drug Res Inst, WELBIO Walloon Excellence Life Sci & BIOtechnol, B-1200 Brussels, Belgium. [Degnan, Fred H.] King & Spalding LLP, Washington, DC USA. [Foster, Jane] McMaster Univ, Hamilton, ON, Canada. [Gibson, Glenn] Univ Reading, Reading, Berks, England. [Hutton, John] Univ York, York YO10 5DD, N Yorkshire, England. [Klaenhammer, Todd R.] N Carolina State Univ, Raleigh, NC 27695 USA. [Ley, Ruth] Cornell Univ, Ithaca, NY USA. [Nieuwdorp, Max] Univ Amsterdam, Amsterdam, Netherlands. [Pot, Bruno] Inst Pasteur, F-59019 Lille, France. [Relman, David] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Serazin, Andrew] Matatu LLC, Washington, DC USA. [Sanders, Mary Ellen] Dairy & Food Culture Technol, Centennial, CO 80122 USA. RP Sanders, ME (reprint author), Dairy & Food Culture Technol, 7119 S Glencoe Ct, Centennial, CO 80122 USA. EM mes@mesanders.com RI Ley, Ruth/M-8542-2014; Cani, Patrice D./M-8055-2016; OI Ley, Ruth/0000-0002-9087-1672; Cani, Patrice D./0000-0003-2040-2448; Dinan, Timothy/0000-0002-2316-7220 FU Ritter Pharmaceuticals FX T. K. is a consultant for Ritter Pharmaceuticals and helped plan the microbiome aspects of the project reported on page 17. M. E. S. consults with numerous food and dietary supplement companies conducting business in the probiotic industry. She does not have any ownership role or serve on governing boards for any company. The other authors declare no conflicts of interest. NR 53 TC 29 Z9 31 U1 6 U2 75 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 2013 VL 1306 BP 1 EP 17 DI 10.1111/nyas.12303 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BJQ15 UT WOS:000329607800001 PM 24266656 ER PT J AU Gandhi, RT Bosch, RJ Aga, E Bedison, MA Bastow, B Schmitz, JL Siliciano, JD Siliciano, RF Eron, JJ Mellors, JW AF Gandhi, Rajesh T. Bosch, Ronald J. Aga, Evgenia Bedison, Margaret A. Bastow, Barbara Schmitz, John L. Siliciano, Janet D. Siliciano, Robert F. Eron, Joseph J. Mellors, John W. CA ACTG A5173 Team TI Residual plasma viraemia and infectious HIV-1 recovery from resting memory CD4 cells in patients on antiretroviral therapy: results from ACTG A5173 SO ANTIVIRAL THERAPY LA English DT Article ID SUBPOPULATIONS AB Background: In HIV-1-infected patients receiving antiretroviral therapy (ART), the relationship between residual viraemia and ex vivo recovery of infectious virus from latently infected CD4 cells is uncertain. Methods: We measured residual viraemia (HIV-1 RNA copies/ml) by single-copy assay (SCA) and the latent reservoir by infectious virus recovery from resting memory CD4 cells (infectious units per million cells [IUPM]) in patients who initiated ART. We assessed immune activation by measuring CD38 expression on T-cells. Results: Ten patients who initiated ART and maintained a plasma HIV-1 RNA level < 200 copies/ml had residual viraemia and IUPM measured every 24 weeks. Five of 10 patients had longitudinal IUPM measured at weeks 24-96; the remainder had IUPM measured 1-3 times over 24-72 weeks. Analyses of 29 paired measurements revealed a positive association between level of residual viraemia and IUPM (0.56 higher log(10) HIV-1 RNA copies/ml per 1 log(10) higher IUPM; P=0.005). Residual viraemia level was positively associated with CD38 density and percentage on CD8(+) T-cells in concurrent samples and with pre-ART HIV-1 RNA levels. Conclusions: In patients with HIV-1 RNA levels < 200 copies/ml 24-96 weeks after initiating ART, the level of viraemia is positively associated with infectious virus recovery from resting memory CD4 cells. Whether this association persists after longer-term suppressive ART needs to be determined. If additional studies show that residual viraemia measured by SCA reflects the size of the latent reservoir in patients who have had virological suppression for longer periods of time, this could facilitate testing of potentially curative strategies to reduce this important reservoir. C1 [Gandhi, Rajesh T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gandhi, Rajesh T.] Ragon Inst, Boston, MA USA. [Bosch, Ronald J.; Aga, Evgenia] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Bedison, Margaret A.; Mellors, John W.] Univ Pittsburgh, Pittsburgh, PA USA. [Bastow, Barbara] Social & Sci Syst Inc, Silver Spring, MD USA. [Schmitz, John L.; Eron, Joseph J.] Univ N Carolina, Chapel Hill, NC USA. [Siliciano, Janet D.; Siliciano, Robert F.] Johns Hopkins Sch Med, Baltimore, MD USA. RP Gandhi, RT (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM rgandhi@partners.org FU Tibotec; Gilead; Merck; GlaxoSmithKline/ViiV FX RTG has received grant support from Tibotec and Gilead. JWM is a consultant for Gilead Sciences and RFS Pharma and owns share options in RFS Pharma. JJE has served as a consultant and received grant support from Merck and GlaxoSmithKline/ViiV and has served as a consultant for Bristol-Myers Squibb, Tibotec, Gilead and Tobira. All other authors declare no competing interests. NR 14 TC 4 Z9 4 U1 0 U2 1 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 2013 VL 18 IS 4 BP 607 EP 613 DI 10.3851/IMP2543 PG 7 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 290MF UT WOS:000329761400009 PM 23411421 ER PT J AU Khatri, P Sit, SP Aceves, M Bose, A Heck, DV Yoo, A AF Khatri, P. Sit, S. P. Aceves, M. Bose, A. Heck, D. V. Yoo, A. CA Penumbra THERAPY Trial Inestigator TI Is Thrombus Length Associated with Baseline Stroke Severity in the Setting of Ischemic Stroke? An Exploratory Analysis SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Khatri, P.] Univ Cincinnati, Cincinnati, OH USA. [Sit, S. P.; Aceves, M.; Bose, A.] Penumbra Inc, Alameda, CA USA. [Heck, D. V.] Forsyth Med Ctr, Winston Salem, NC USA. [Yoo, A.] Massachusets Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2013 VL 35 SU 3 BP 14 EP 14 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 281HZ UT WOS:000329092600010 ER PT J AU Sirimarco, G Amarenco, P Labreuche, J Touboul, PJ Alberts, M Goto, S Rother, J Mas, JL Bhatt, DL Steg, PG AF Sirimarco, G. Amarenco, P. Labreuche, J. Touboul, P. J. Alberts, M. Goto, S. Rother, J. Mas, J. L. Bhatt, D. L. Steg, P. G. TI Carotid Atherosclerosis and Risk of Subsequent Coronary Event in Outpatients with Atherothrombosis SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Sirimarco, G.; Amarenco, P.; Labreuche, J.; Touboul, P. J.] Univ Paris Diderot, Dept Neurol, Paris, France. [Sirimarco, G.; Amarenco, P.; Labreuche, J.; Touboul, P. J.] Univ Paris Diderot, Stroke Ctr, Bichat Claude Bernard Hosp, Paris, France. [Alberts, M.] Northwestern Univ, Sch Med, Dept Neurol, Chicago, IL 60611 USA. [Goto, S.] Tokai Univ, Sch Med, Dept Med Cardiol, Isehara, Kanagawa 25911, Japan. [Rother, J.] Hannover Med Sch, Dept Neurol, Klinikum Minden, Minden, Germany. [Mas, J. L.] Paris Descartes Univ, Stroke Unit, Dept Neurol, St Anne Hosp, Paris, France. [Bhatt, D. L.] Harvard Univ, Brigham & Womens Hosp, VA Boston Healthcare Syst, Sch Med, Boston, MA 02115 USA. [Steg, P. G.] Univ Paris Diderot, Bichat Claude Bernard Hosp, Dept Cardiol, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2013 VL 35 SU 3 BP 25 EP 25 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 281HZ UT WOS:000329092600025 ER PT J AU Lorenzano, S Rost, NS Li, H Chutinet, A Green, RE Thankachan, T Thornell, B Arai, K Wu, O Harris, GJ Lo, EH Blumberg, JB Feske, SK Furie, KL AF Lorenzano, S. Rost, N. S. Li, H. Chutinet, A. Green, R. E. Thankachan, T. Thornell, B. Arai, K. Wu, O. Harris, G. J. Lo, E. H. Blumberg, J. B. Feske, S. K. Furie, K. L. TI Molecular Correlates of Neuroimaging Findings in Acute Ischemic Stroke: Early Oxidative Stress Biomarkers of Ischemic Penumbra SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Lorenzano, S.; Rost, N. S.; Li, H.; Chutinet, A.; Green, R. E.; Thankachan, T.; Thornell, B.; Arai, K.; Wu, O.; Harris, G. J.; Lo, E. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lorenzano, S.; Rost, N. S.; Li, H.; Chutinet, A.; Green, R. E.; Thankachan, T.; Thornell, B.; Arai, K.; Wu, O.; Harris, G. J.; Lo, E. H.; Feske, S. K.] Harvard Univ, Sch Med, Boston, MA USA. [Blumberg, J. B.] Tufts Univ, Boston, MA 02111 USA. [Feske, S. K.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Furie, K. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Furie, K. L.] Brown Univ, Rhode Isl Hosp, Alpert Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2013 VL 35 SU 3 BP 32 EP 32 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 281HZ UT WOS:000329092600036 ER PT J AU Cheng, B Brinkmann, M Forkert, ND Treszl, A Ebinger, M Kohrmann, M Wu, O Kang, DW Liebeskind, DS Tourdias, T Singer, OC Christensen, S Luby, M Gerloff, C Thomalla, G AF Cheng, B. Brinkmann, M. Forkert, N. D. Treszl, A. Ebinger, M. Koehrmann, M. Wu, O. Kang, D. W. Liebeskind, D. S. Tourdias, T. Singer, O. C. Christensen, S. Luby, M. Gerloff, C. Thomalla, G. CA STIR & VISTA Imaging Investigators TI Quantitative measurements of relative fluid-attenuated inversion recovery (FLAIR) signal intensities in acute stroke do not improve accuracy of estimation of lesion age SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Cheng, B.; Brinkmann, M.; Gerloff, C.; Thomalla, G.] Klin & Poliklin Neurol Kopf & Neurozentrum, Hamburg, Germany. [Forkert, N. D.] Unversite Klinikum Hamburg Eppendorf, Inst Computat Neurosci, Hamburg, Germany. [Treszl, A.] Unversite Klinikum Hamburg Eppendorf, Inst Med Biometrie & Epidemiol, Hamburg, Germany. [Ebinger, M.] Charite, Ctr Schlaganfallforsch Berlin, D-13353 Berlin, Germany. [Koehrmann, M.] Univ Erlangen Nurnberg, Neurol Klin, D-91054 Erlangen, Germany. [Wu, O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula MartinosCtr Biomed Imaging,Dept Radiol, Boston, MA USA. [Kang, D. W.] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Neurol, Seoul, South Korea. [Liebeskind, D. S.] Univ Calif Oakland, Dept Neurol, Oakland, CA USA. [Tourdias, T.] Univ Bordeaux, Serv NeuroImagerie Diagnost Therapeut, CHU Bordeaux, Bordeaux, France. [Singer, O. C.] Univ Klinikum Erlangen Nurnberg, Kliniken Neuroradiol, Erlangen, Germany. [Christensen, S.] Univ Melbourne, Royal Melbourne Hosp, Dept Neurol, Parkville, Vic, Australia. [Luby, M.] Inst Neurol Disorders & Stroke, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2013 VL 35 SU 3 BP 44 EP 44 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 281HZ UT WOS:000329092600052 ER PT J AU Jaillard, A Hommel, M Le Bas, JF Zeffiro, TA AF Jaillard, A. Hommel, M. Le Bas, J. F. Zeffiro, T. A. TI Brain reorganization within the motor network supports motor recovery following acute and chronic cerebellar stroke: a fMRI study SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Jaillard, A.; Hommel, M.; Le Bas, J. F.] Grenoble Univ Hosp, Grenoble, France. [Zeffiro, T. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2013 VL 35 SU 3 BP 99 EP 99 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 281HZ UT WOS:000329092600130 ER PT J AU Brouwers, HB Raffeld, MR Falcone, GJ Ayres, AM Schwab, K Romero, JM Viswanathan, A Greenberg, SM Ogilvy, CS Goldstein, JN Rosand, J AF Brouwers, H. B. Raffeld, M. R. Falcone, G. J. Ayres, A. M. Schwab, K. Romero, J. M. Viswanathan, A. Greenberg, S. M. Ogilvy, C. S. Goldstein, J. N. Rosand, J. TI CT Angiography Spot Sign Predicts Perioperative Bleeding in Primary Intracerebral Hemorrhage SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Brouwers, H. B.; Raffeld, M. R.; Falcone, G. J.; Ayres, A. M.; Schwab, K.; Romero, J. M.; Viswanathan, A.; Greenberg, S. M.; Ogilvy, C. S.; Goldstein, J. N.; Rosand, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RI Goldstein, Joshua/H-8953-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2013 VL 35 SU 3 BP 129 EP 129 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 281HZ UT WOS:000329092600179 ER PT J AU Lorenzano, S Rost, NS Arai, K Batista, L Thankachan, T Green, RE Som, AT Harris, GJ Blumberg, JB Feske, SK Lo, EH Furie, KL AF Lorenzano, S. Rost, N. S. Arai, K. Batista, L. Thankachan, T. Green, R. E. Som, A. T. Harris, G. J. Blumberg, J. B. Feske, S. K. Lo, E. H. Furie, K. L. TI Role of Plasma Biomarkers in Diagnosis of Ischemic Stroke Subtypes SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Lorenzano, S.; Rost, N. S.; Arai, K.; Batista, L.; Thankachan, T.; Green, R. E.; Som, A. T.; Harris, G. J.; Feske, S. K.; Lo, E. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lorenzano, S.; Rost, N. S.; Arai, K.; Batista, L.; Thankachan, T.; Green, R. E.; Som, A. T.; Harris, G. J.; Feske, S. K.; Lo, E. H.] Harvard Univ, Sch Med, Boston, MA USA. [Blumberg, J. B.] Tufts Univ, Boston, MA 02111 USA. [Furie, K. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Furie, K. L.] Brown Univ, Rhode Isl Hosp, Alpert Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2013 VL 35 SU 3 BP 256 EP 256 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 281HZ UT WOS:000329092600381 ER PT J AU Frei, DF Yoo, AJ Heck, D Hellinger, F McCollom, V Fiorella, D Turk, A Malisch, T Zaidat, O Alexander, M Chaudhry, ZA Gonzalez, RG Barraza, L Bose, A Sit, SP AF Frei, D. F. Yoo, A. J. Heck, D. Hellinger, F., II McCollom, V. Fiorella, D. Turk, A., III Malisch, T. Zaidat, O. Alexander, M. Chaudhry, Z. A. Gonzalez, R. G. Barraza, L. Bose, A. Sit, S. P. CA START Investigators TI Importance of pre-treatment neuroimaging in identifying acute stroke patients with large infarcts who are unlikely to respond to IA therapy SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Frei, D. F.] Swedish Med Ctr, Englewood, CO 80110 USA. [Yoo, A. J.; Chaudhry, Z. A.; Gonzalez, R. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Heck, D.] Forsyth Med Ctr, Winston Salem, NC USA. [Hellinger, F., II] Florida Hosp, Orlando, FL USA. [McCollom, V.] Mercy Hlth Ctr, Oklahoma City, OK USA. [Fiorella, D.] Stony Brook Med Ctr, Stony Brook, NY USA. [Turk, A., III] Med Univ S Carolina, Charleston, SC USA. [Malisch, T.] Alexian Bros Med Ctr, Elk Grove Village, IL USA. [Zaidat, O.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Alexander, M.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Barraza, L.; Bose, A.; Sit, S. P.] Penumbra Inc, Alameda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2013 VL 35 SU 3 BP 277 EP 277 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 281HZ UT WOS:000329092601001 ER PT J AU Rannikmae, K Kalaria, RN Greenberg, SM Chui, HC Schmitt, FA Sudlow, CLM AF Rannikmaee, K. Kalaria, R. N. Greenberg, S. M. Chui, H. C. Schmitt, F. A. Sudlow, C. L. M. TI Association between APOE genotype and CAA related vasculopathic changes - collaborative meta-analysis SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Rannikmaee, K.; Sudlow, C. L. M.] Univ Edinburgh, Div Clin Neurosci, Edinburgh, Midlothian, Scotland. [Kalaria, R. N.] Newcastle Univ, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Greenberg, S. M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Chui, H. C.] Univ So Calif, Dept Neurol, Los Angeles, CA USA. [Schmitt, F. A.] Univ Kentucky, Dept Neurol, Sanders Brown Ctr Aging, Lexington, KY 40506 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2013 VL 35 SU 3 BP 435 EP 435 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 281HZ UT WOS:000329092601274 ER PT J AU Campos, F Qin, T Castillo, J Seo, JH Arai, K Lo, EH Waeber, C AF Campos, F. Qin, T. Castillo, J. Seo, J. H. Arai, K. Lo, E. H. Waeber, C. TI FINGOLIMOD REDUCES HEMORRHAGIC TRANSFORMATION ASSOCIATED WITH DELAYED TISSUE PLASMINOGEN ACTIVATOR TREATMENT IN A MOUSE THROMBOEMBOLIC MODEL. SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Campos, F.; Castillo, J.] Hosp Clin Univ, Dept Neurol, Clin Neurosci Res Lab, IDIS, Santiago De Compostela, Spain. [Qin, T.] Massachusetts Gen Hosp, Dept Radiol, Stroke Res Lab, Boston, MA 02114 USA. [Seo, J. H.; Arai, K.; Lo, E. H.] Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Boston, MA 02114 USA. [Seo, J. H.; Arai, K.; Lo, E. H.] Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Boston, MA 02114 USA. [Waeber, C.] Natl Univ Ireland Univ Coll Cork, Sch Pharm, Cork, Ireland. RI Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2013 VL 35 SU 3 BP 545 EP 545 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 281HZ UT WOS:000329092601472 ER PT J AU Lorenzano, S Rost, NS Li, H Lima, FO Maas, MB Dipietro, AJ Arai, K Toni, D Wu, O Harris, GJ Lo, EH Blumberg, JB Feske, SK Furie, KL AF Lorenzano, S. Rost, N. S. Li, H. Lima, F. O. Maas, M. B. Dipietro, A. J. Arai, K. Toni, D. Wu, O. Harris, G. J. Lo, E. H. Blumberg, J. B. Feske, S. K. Furie, K. L. TI Role of Oxidative Stress in Mediating Vascular Brain Damage: Hyperacute Plasma F2-Isoprostane Predicts Infarct Growth in Ischemic Stroke SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Lorenzano, S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Lorenzano, S.] Sapienza Univ Rome, Boston, MA USA. [Rost, N. S.; Li, H.; Lima, F. O.; Maas, M. B.; Dipietro, A. J.; Arai, K.; Wu, O.; Harris, G. J.; Lo, E. H.; Feske, S. K.; Furie, K. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rost, N. S.; Li, H.; Lima, F. O.; Maas, M. B.; Dipietro, A. J.; Arai, K.; Wu, O.; Harris, G. J.; Lo, E. H.; Feske, S. K.; Furie, K. L.] Harvard Univ, Sch Med, Boston, MA USA. [Toni, D.] Univ Roma La Sapienza, I-00185 Rome, Italy. [Blumberg, J. B.] Tufts Univ, Boston, MA 02111 USA. RI Lima, Fabricio/E-6507-2015 OI Lima, Fabricio/0000-0002-0383-4145 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2013 VL 35 SU 3 BP 551 EP 551 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 281HZ UT WOS:000329092601484 ER PT J AU Hemmen, M Lee, JM Middleton, S Randall, M Rost, NS Rinkel, GJE Bottle, A AF Hemmen, M. Lee, J. M. Middleton, S. Randall, M. Rost, N. S. Rinkel, G. J. E. Bottle, A. TI Comparing disability and mortality following ischemic stroke in the UK and US SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Hemmen, M.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Lee, J. M.] Washington Univ, St Louis, MO USA. [Middleton, S.] Dr Foster Intelligence, London, England. [Randall, M.] Univ Sheffield, Sheffield, S Yorkshire, England. [Rost, N. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rinkel, G. J. E.] UMC Utrecht, Utrecht, Netherlands. [Bottle, A.] Univ London Imperial Coll Sci Technol & Med, Dr Foster Unit, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2013 VL 35 SU 3 BP 691 EP 691 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 281HZ UT WOS:000329092602229 ER PT J AU Falcone, GF Brouwers, HB Biffi, A Anderson, CD Battey, TWK Ayres, AM Vashkevich, A Schwab, K Rost, NS Goldstein, JN Viswanathan, A Greenberg, SM Rosand, J AF Falcone, G. F. Brouwers, H. B. Biffi, A. Anderson, C. D. Battey, T. W. K. Ayres, A. M. Vashkevich, A. Schwab, K. Rost, N. S. Goldstein, J. N. Viswanathan, A. Greenberg, S. M. Rosand, J. TI Predictors of Hematoma Volume in Primary Infratentorial Intracerebral Hemorrhage SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Falcone, G. F.; Brouwers, H. B.; Biffi, A.; Anderson, C. D.; Battey, T. W. K.; Ayres, A. M.; Vashkevich, A.; Schwab, K.; Rost, N. S.; Goldstein, J. N.; Viswanathan, A.; Greenberg, S. M.; Rosand, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Goldstein, Joshua/H-8953-2016 NR 0 TC 0 Z9 0 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2013 VL 35 SU 3 BP 807 EP 807 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 281HZ UT WOS:000329092602435 ER PT J AU Brouwers, HB Chang, Y Falcone, GJ Ayres, AM McNamara, KA Vashkevich, A Battey, TW Valant, V Schwab, K Rost, NS Romero, JM Viswanathan, A Greenberg, SM Rosand, J Goldstein, JN AF Brouwers, H. B. Chang, Y. Falcone, G. J. Ayres, A. M. McNamara, K. A. Vashkevich, A. Battey, T. W. Valant, V. Schwab, K. Rost, N. S. Romero, J. M. Viswanathan, A. Greenberg, S. M. Rosand, J. Goldstein, J. N. TI A Prediction Score for Hematoma Expansion Following Acute Intracerebral Hemorrhage SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Brouwers, H. B.; Chang, Y.; Falcone, G. J.; Ayres, A. M.; McNamara, K. A.; Vashkevich, A.; Battey, T. W.; Valant, V.; Schwab, K.; Rost, N. S.; Romero, J. M.; Viswanathan, A.; Greenberg, S. M.; Rosand, J.; Goldstein, J. N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RI Goldstein, Joshua/H-8953-2016 NR 0 TC 0 Z9 0 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2013 VL 35 SU 3 BP 814 EP 814 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 281HZ UT WOS:000329092602447 ER PT J AU Favre, I Jaillard, A Zeffiro, T Krainik, A Detante, O Hommel, M AF Favre, I. Jaillard, A. Zeffiro, T. Krainik, A. Detante, O. Hommel, M. TI ALE meta-analysis of motor task-related activation in functional brain imaging after acute and chronic stroke SO CEREBROVASCULAR DISEASES LA English DT Meeting Abstract C1 [Favre, I.; Jaillard, A.; Detante, O.; Hommel, M.] CHU Grenoble, F-38043 Grenoble, France. [Zeffiro, T.] Harvard Univ, Massachussets Gen Hosp, Martinos Ctr, Boston, MA 02115 USA. RI KRAINIK, Alexandre/L-5874-2014; Detante, Olivier/M-1737-2014 NR 0 TC 0 Z9 0 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 EI 1421-9786 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2013 VL 35 SU 3 BP 822 EP 822 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 281HZ UT WOS:000329092602463 ER PT J AU Allegretti, AS Steele, DJR David-Kasdan, JA Bajwa, E Niles, JL Bhan, I AF Allegretti, Andrew S. Steele, David J. R. David-Kasdan, Jo Ann Bajwa, Ednan Niles, John L. Bhan, Ishir TI Continuous renal replacement therapy outcomes in acute kidney injury and end-stage renal disease: a cohort study SO CRITICAL CARE LA English DT Article DE continuous renal replacement therapy; mortality; acute kidney injury; end stage renal disease; dialysis; dialysis-free survival ID INTENSIVE-CARE-UNIT; LONG-TERM SURVIVAL; CRITICALLY-ILL PATIENTS; RESPIRATORY-DISTRESS-SYNDROME; GENERAL-POPULATION; FLUID ACCUMULATION; FAILURE; MORTALITY; RECOVERY; ICU AB Introduction: Continuous renal replacement therapy (CRRT) is a widely used but resource-intensive treatment. Despite its broad adoption in intensive care units (ICUs), it remains challenging to identify patients who would be most likely to achieve positive outcomes with this therapy and to provide realistic prognostic information to patients and families. Methods: We analyzed a prospective cohort of all 863 ICU patients initiated on CRRT at an academic medical center from 2008 to 2011 with either new-onset acute kidney injury (AKI) or pre-admission end-stage renal disease (ESRD). We examined in-hospital and post-discharge mortality (for all patients), as well as renal recovery (for AKI patients). We identified prognostic factors for both in-hospital and post-discharge mortality separately in patients with AKI or ESRD. Results: In-hospital mortality was 61% for AKI and 54% for ESRD. In patients with AKI (n = 725), independent risk factors for mortality included age over 60 (OR 1.9, 95% CI 1.3, 2.7), serum lactate over 4 mmol/L (OR 2.2, 95% CI 1.5, 3.1), serum creatinine over 3 mg/dL at time of CRRT initiation (OR 0.63, 95% CI 0.43, 0.92) and comorbid liver disease (OR 1.75, 95% CI 1.1, 2.9). Among patients with ESRD (n = 138), liver disease was associated with increased mortality (OR 3.4, 95% CI 1.1, 11.1) as was admission to a medical (vs surgical) ICU (OR 2.2, 95% CI 1.1, 4.7). Following discharge, advanced age became a predictor of mortality in both groups (AKI: HR 1.9, 95% CI 1.2, 3.0; ESRD: HR 4.1, 95% CI 1.5, 10.9). At the end of the study period, only 25% (n = 183) of patients with AKI achieved dialysis-free survival. Conclusions: Among patients initiating CRRT, risk factors for mortality differ between patients with underlying ESRD or newly acquired AKI. Long-term dialysis-free survival in AKI is low. Providers should consider these factors when assessing prognosis or appropriateness of CRRT. C1 [Allegretti, Andrew S.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Steele, David J. R.; David-Kasdan, Jo Ann; Niles, John L.; Bhan, Ishir] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Bajwa, Ednan] Massachusetts Gen Hosp, Dept Med, Divs Pulm & Crit Care Med, Boston, MA 02114 USA. RP Bhan, I (reprint author), Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. EM ibhan@partners.org FU National Institutes of Health [5K23DK081677, K23HL087934] FX IB is supported by a grant from the National Institutes of Health (5K23DK081677). EB is supported by a grant from the National Institutes of Health (K23HL087934). NR 37 TC 11 Z9 15 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X EI 1364-8535 J9 CRIT CARE JI Crit. Care PY 2013 VL 17 IS 3 AR R109 DI 10.1186/cc12780 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 285YN UT WOS:000329431100026 PM 23782899 ER PT J AU Esch, T Fricchione, GL Joos, S Teut, M AF Esch, Tobias Fricchione, Gregory L. Joos, Stefanie Teut, Michael TI Self-Care, Stress Management, and Primary Care: From Salutogenesis and Health Promotion to Mind-Body Medicine SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Editorial Material C1 [Esch, Tobias] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Esch, Tobias] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Esch, Tobias] Coburg Univ Appl Sci, Div Integrat Hlth Promot, D-96450 Coburg, Germany. [Fricchione, Gregory L.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Fricchione, Gregory L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Joos, Stefanie] Univ Heidelberg Hosp, Dept Gen Practice & Hlth Serv Res, D-69115 Heidelberg, Germany. [Teut, Michael] Charite, Inst Social Med Epidemiol & Hlth Econ, D-10117 Berlin, Germany. RP Esch, T (reprint author), Harvard Univ, Sch Med, Boston, MA 02215 USA. EM tesch@bidmc.harvard.edu RI Esch, Tobias/J-3812-2013 OI Joos, Stefanie/0000-0002-5810-529X; Esch, Tobias/0000-0001-5176-4367 NR 6 TC 1 Z9 1 U1 0 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1741-427X EI 1741-4288 J9 EVID-BASED COMPL ALT JI Evid.-based Complement Altern. Med. PY 2013 AR 327415 DI 10.1155/2013/327415 PG 2 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 288XF UT WOS:000329644700001 ER PT J AU Khorsan, R Cohen, AB Lisi, AJ Smith, MM Delevan, D Armstrong, C Mittman, BS AF Khorsan, Raheleh Cohen, Angela B. Lisi, Anthony J. Smith, Monica M. Delevan, Deborah Armstrong, Courtney Mittman, Brian S. TI Mixed-Methods Research in a Complex Multisite VA Health Services Study: Variations in the Implementation and Characteristics of Chiropractic Services in VA SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Article ID ALTERNATIVE MEDICINE USE; EVALUATING QUALITY; MILITARY VETERANS; UNITED-STATES; TEAM SCIENCE; CARE-SYSTEM; CASE SERIES; COMPLEMENTARY; TRENDS; MANAGEMENT AB Maximizing the quality and benefits of newly established chiropractic services represents an important policy and practice goal for the US Department of Veterans Affairs' healthcare system. Understanding the implementation process and characteristics of new chiropractic clinics and the determinants and consequences of these processes and characteristics is a critical first step in guiding quality improvement. This paper reports insights and lessons learned regarding the successful application of mixed methods research approaches-insights derived from a study of chiropractic clinic implementation and characteristics, Variations in the Implementation and Characteristics of Chiropractic Services in VA (VICCS). Challenges and solutions are presented in areas ranging from selection and recruitment of sites and participants to the collection and analysis of varied data sources. The VICCS study illustrates the importance of several factors in successful mixed-methods approaches, including (1) the importance of a formal, fully developed logic model to identify and link data sources, variables, and outcomes of interest to the study's analysis plan and its data collection instruments and codebook and (2) ensuring that data collection methods, including mixed-methods, match study aims. Overall, successful application of a mixed-methods approach requires careful planning, frequent trade-offs, and complex coding and analysis. C1 [Khorsan, Raheleh; Cohen, Angela B.; Smith, Monica M.; Delevan, Deborah; Mittman, Brian S.] VA Greater Los Angeles Healthcare Syst, VA Ctr Implementat Practice & Res Support, Los Angeles, CA 91343 USA. [Khorsan, Raheleh] Samueli Inst, Mil Med Res Program, Corona Del Mar, CA USA. [Lisi, Anthony J.] Vet Hlth Adm, Patient Care Serv, Chiropract Program, Washington, DC USA. [Lisi, Anthony J.] VA Connecticut Healthcare Syst, Chiropract Serv, West Haven, CT USA. [Armstrong, Courtney] RAND Corp, Boston, MA USA. RP Mittman, BS (reprint author), VA Greater Los Angeles Healthcare Syst, VA Ctr Implementat Practice & Res Support, 16111 Plummer St, Los Angeles, CA 91343 USA. EM brian.mittman@va.gov OI Cohen, Angela B./0000-0002-0620-1909 FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research Development Service; Samueli Institute; US Army Medical Research and Materiel Command [W81XWH-06-1-0279]; National Institutes of Health National Center for Complementary and Alternative Medicine (NIH-NCCAM) [K01-AT002391] FX The authors would like to acknowledge Joan A. Walter, J.D., P. A., and Rick Welton, M. D., for their support and contributions to the project. They would also like to acknowledge the members of the project advisory board: Lucille Beck, Ph.D.; Charles Burgar, M. D.; A. Lucile Burgo-Black, M. D.; Ian Coulter, Ph.D.; Paul Shekelle, M. D., Ph.D.; Joan Walter, J.D., P. A. Oral presentations by (1) Khorsan R, Cohen A, Smith M, Lisi A, Mittman B, Coulter I, and Walter J. Integrative Chiropractic Services in VA: A Pilot Study (VICCS). American Public Health Association (APHA) 140th Annual Meeting and Exposition, Session: 3418.0 Policy, regulation, comparative and cost effectiveness research: San Francisco, CA. Monday, October 29, 2012: 5: 15 p. m. (Abstract no. 269497); (2) Cohen A, Smith M, Khorsan R, Lisi A, Mittman B, Jenkins D, and Armstrong C. Methodological and logistical challenges to conducting multi-site partnered research in the VA healthcare system. American Public Health Association (APHA) 140th Annual Meeting and Exposition, Session: 3323.0 Chiropractic Research: Current status and updates: San Francisco, CA. Monday, October 29, 2012: 3: 00 PM. (Abstract no. 268597); (3) Smith M, Cohen A, Khorsan R, Jenkins D, Armstrong C, Lisi A, and Mittman B. Tracking VA's chiropractic program: Implementation timelines and variations across selected facilities. American Public Health Association (APHA) 140th Annual Meeting and Exposition, Session: 4133.1 Veteran's Health Care and Health Risks: San Francisco, CA. Tuesday, October 30, 2012: 11: 30 PM. (Abstract no. 265497); (4) Lisi A, Mittman B, Khorsan R, Smith S, Cohen A, Armstrong C, MacGregor C, Carucci M, and Jenkins DM. Variations in the Implementation and Characteristics of Chiropractic Services in VA: A Pilot Study. Association of Chiropractic Colleges (ACC) and Research Agenda Conference (RAC): Las Vegas, NV. March 20-21, 2012; (5) Lisi A, Mittman B, Khorsan R, Smith S, Cohen A, Armstrong C, MacGregor C, Carucci M, and Jenkins DM. Studying the introduction, integration, and effectiveness of chiropractic services within the VA healthcare system: A novel clinical/research collaboration. Association of Chiropractic Colleges (ACC) and Research Agenda Conference (RAC): Las Vegas, NV. March 19-21, 2011; and (6) Lisi A, Mittman B, Khorsan R, Smith S, Cohen A, Armstrong C, MacGregor C, Carucci M, and Jenkins DM. Variations in the implementation and characteristics of chiropractic services in VA Association of Chiropractic Colleges (ACC) and Research Agenda Conference (RAC): Las Vegas, NV. March 19-21, 2011. This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Health Services Research Development Service. The views expressed in this paper are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. In addition, this work was supported, in part, by a grant to Brian S. Mittman by the Samueli Institute. This grant is supported by the US Army Medical Research and Materiel Command under Award no. W81XWH-06-1-0279. The views, opinions, and/or findings contained in this report are those of the author(s) and should not be construed as an official position, policy, or decision of Department of the Army unless so designated by other documentation.; Also, the views, opinions, and/or findings contained in this report are those of the author(s) and should not be construed as the opinion or policy of the Samueli Institute. In the conduct of research where humans are the subjects, the investigator(s) adhered to the policies regarding the protection of human subjects as prescribed by Code of Federal Regulations (CFR) Title 45, Volume 1, Part 46; Title 32, Chapter 1, Part 219; and Title 21, Chapter 1, Part 50 (Protection of Human Subjects). Monica M. Smith was supported in this work by Grant no. K01-AT002391, a grant from National Institutes of Health National Center for Complementary and Alternative Medicine (NIH-NCCAM). Study findings and conclusions are those of the authors and do not represent the opinion or position of NIH or NCCAM. Institutional review board (IRB) approvals were by VA Greater Los Angeles Healthcare System (IRB of record), VA Connecticut Healthcare System(IRB for Co-PI), Western IRB (IRB for Samueli Institute), and US Army Medical Research and Materiel Command (IRB for Department of Defense). NR 55 TC 2 Z9 2 U1 3 U2 3 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1741-427X EI 1741-4288 J9 EVID-BASED COMPL ALT JI Evid.-based Complement Altern. Med. PY 2013 AR 701280 DI 10.1155/2013/701280 PG 10 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 289XI UT WOS:000329715500001 ER PT J AU Liu, S Ren, JA Hong, ZW Li, XT Yao, M Yan, DS Ren, HJ Wu, XW Wang, GF Gu, GS Xia, QY Han, G Li, JS AF Liu, Song Ren, Jianan Hong, Zhiwu Li, Xiaoting Yao, Min Yan, Dongsheng Ren, Huajian Wu, Xiuwen Wang, Gefei Gu, Guosheng Xia, Qiuyuan Han, Gang Li, Jieshou TI An Evil Backstage Manipulator: Psychological Factors Correlated with Health-Related Quality of Life in Chinese Patients with Crohn's Disease SO SCIENTIFIC WORLD JOURNAL LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; ULCERATIVE-COLITIS; DISTRESSED PATIENTS; HOSPITAL ANXIETY; FOLLOW-UP; AGGRESSION QUESTIONNAIRE; DEPRESSION SCALE; CLINICAL-TRIALS; SINGLE-CENTER; PERSONALITY AB Health-related quality of life (HRQoL) is recommended as one of essential parameters to evaluate treatment effect and clinical outcome in patients with Crohn's disease (CD). Recent studies reported that psychological factors might play a role in HRQoL in Western and American CD patients. Sufficient evidences in Chinese CD patients are still unavailable. This study is dedicated to investigate the correlation of various psychological factors with HRQoL in Chinese CD patients. We prospectively collected 40 active and 40 quiescent CD patients in China and found that psychological factors, especially neuroticism and anxiety, significantly correlate with and affect HRQoL in both active and quiescent CD groups. This is the first report revealing correlation between psychological factors and HRQoL in Chinese CD patients. Therefore, we assume that our results can contribute to a better understanding of etiology and tailoring of management in Chinese patients with Crohn's disease and are beneficial to our colleagues to compare the heterogeneous characteristics of Crohn's disease in different ethnic groups. C1 [Liu, Song; Ren, Jianan; Hong, Zhiwu; Yan, Dongsheng; Ren, Huajian; Wu, Xiuwen; Wang, Gefei; Gu, Guosheng; Li, Jieshou] Nanjing Univ, Sch Med, Jinling Hosp, Dept Surg, Nanjing 210002, Jiangsu, Peoples R China. [Liu, Song] Massachusetts Gen Hosp, Dept Med, GI Unit, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Liu, Song] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Li, Xiaoting] Nanjing Univ Chinese Med, Jinling Hosp, Dept Surg, Coll Nursing, Nanjing 210002, Jiangsu, Peoples R China. [Yao, Min] VA New England Hlth Care Div, Dept Surg Limb Preservat & Wound Care Res, Providence, RI 02908 USA. [Xia, Qiuyuan] Nanjing Univ, Jinling Hosp, Dept Pathol, Sch Med, Nanjing 210002, Jiangsu, Peoples R China. [Han, Gang] Jilin Univ, Affiliated Hosp 2, Dept Gen Surg, Gen Surg Ctr, Changchun 130000, Peoples R China. RP Ren, JA (reprint author), Nanjing Univ, Sch Med, Jinling Hosp, Dept Surg, Nanjing 210002, Jiangsu, Peoples R China. EM jiananr@gmail.com FU National Natural Science Foundation of China [81270478]; Climbing Program in Natural Science Foundation of Jiangsu Province for Distinguished Scholars [BK2010017]; High-Level Personnel Training Project [BRA2011232]; China Scholarship Council FX This work was supported by Grants from National Natural Science Foundation of China, no. 81270478 (Jianan Ren); Climbing Program in Natural Science Foundation of Jiangsu Province for Distinguished Scholars no. BK2010017 (Jianan Ren); High-Level Personnel Training Project, no. BRA2011232 (Jianan Ren), and China Scholarship Council (award to Song Liu for study at Massachusetts General Hospital, Harvard Medical School). The authors would like to thank Dr. Madhulika Varma (UCSF Medical Center) and Dr. Jessica Cohan (UCSF Medical Center) for their critical review of this paper and precious advice. NR 38 TC 1 Z9 1 U1 1 U2 12 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1537-744X J9 SCI WORLD J JI Sci. World J. PY 2013 AR 464698 DI 10.1155/2013/464698 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 289FZ UT WOS:000329668400001 ER PT J AU Thomssen, C Diel, I Gnant, M Goldmann-Posch, U Goschke, C Haidinger, R Janni, W Lin, NU AF Thomssen, Christoph Diel, Ingo Gnant, Michael Goldmann-Posch, Ursula Goeschke, Christiane Haidinger, Renate Janni, Wolfgang Lin, Nancy U. TI Follow-Up after Breast Cancer Diagnosis SO BREAST CARE LA English DT Editorial Material C1 [Thomssen, Christoph] Univ Halle Wittenberg, Dept Gynecol, D-06097 Halle, Germany. [Diel, Ingo] Praxisklin Rosengarten, Mannheim, Germany. [Gnant, Michael] Med Univ Vienna, Ctr Comprehens Canc, Dept Surg, Vienna, Austria. [Goldmann-Posch, Ursula] Mamazone & PONS Fdn, Augsburg, Germany. [Goeschke, Christiane] Europa Donna Austria, Vienna, Austria. [Haidinger, Renate] Brustkrebs Deutschland eV, Hohenbrunn, Germany. [Janni, Wolfgang] Univ Ulm, Dept Obstet & Gynecol, D-89069 Ulm, Germany. [Lin, Nancy U.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Thomssen, C (reprint author), Univ Halle Wittenberg, Klin & Poliklin Gynakol, Ernst Grube Str 40, D-06097 Halle, Germany. EM christoph.thomssen@medizin.uni-halle.de OI Gnant, Michael/0000-0003-1002-2118 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-3791 EI 1661-3805 J9 BREAST CARE JI Breast Care PY 2013 VL 8 IS 6 BP 457 EP 460 DI 10.1159/000357586 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 287BY UT WOS:000329514500013 PM 24550757 ER PT J AU Yen, J White, RM Wedge, DC Van Loo, P de Ridder, J Capper, A Richardson, J Jones, D Raine, K Watson, IR Wu, CJ Cheng, JQ Martincorena, I Nik-Zainal, S Mudie, L Moreau, Y Marshall, J Ramakrishna, M Tarpey, P Shlien, A Whitmore, I Gamble, S Latimer, C Langdon, E Kaufman, C Dovey, M Taylor, A Menzies, A McLaren, S O'Meara, S Butler, A Teague, J Lister, J Chin, L Campbell, P Adams, DJ Zon, LI Patton, EE Stemple, DL Futreal, PA AF Yen, Jennifer White, Richard M. Wedge, David C. Van Loo, Peter de Ridder, Jeroen Capper, Amy Richardson, Jennifer Jones, David Raine, Keiran Watson, Ian R. Wu, Chang-Jiun Cheng, Jiqiu Martincorena, Inigo Nik-Zainal, Serena Mudie, Laura Moreau, Yves Marshall, John Ramakrishna, Manasa Tarpey, Patrick Shlien, Adam Whitmore, Ian Gamble, Steve Latimer, Calli Langdon, Erin Kaufman, Charles Dovey, Mike Taylor, Alison Menzies, Andy McLaren, Stuart O'Meara, Sarah Butler, Adam Teague, Jon Lister, James Chin, Lynda Campbell, Peter Adams, David J. Zon, Leonard I. Patton, E. Elizabeth Stemple, Derek L. Futreal, P. Andy TI The genetic heterogeneity and mutational burden of engineered melanomas in zebrafish models SO GENOME BIOLOGY LA English DT Article ID INTEGRATIVE GENOMICS VIEWER; TERT PROMOTER MUTATIONS; SOMATIC MUTATIONS; CARNEY COMPLEX; RECEPTOR GENES; BRAF MUTATIONS; BREAST-CANCER; PROTEIN; TUMORS; TUMORIGENESIS AB Background: Melanoma is the most deadly form of skin cancer. Expression of oncogenic BRAF or NRAS, which are frequently mutated in human melanomas, promote the formation of nevi but are not sufficient for tumorigenesis. Even with germline mutated p53, these engineered melanomas present with variable onset and pathology, implicating additional somatic mutations in a multi-hit tumorigenic process. Results: To decipher the genetics of these melanomas, we sequence the protein coding exons of 53 primary melanomas generated from several BRAF(V600E) or NRAS(Q61K) driven transgenic zebrafish lines. We find that engineered zebrafish melanomas show an overall low mutation burden, which has a strong, inverse association with the number of initiating germline drivers. Although tumors reveal distinct mutation spectrums, they show mostly C > T transitions without UV light exposure, and enrichment of mutations in melanogenesis, p53 and MAPK signaling. Importantly, a recurrent amplification occurring with pre-configured drivers BRAF(V600E) and p53(-/-) suggests a novel path of BRAF cooperativity through the protein kinase A pathway. Conclusion: This is the first analysis of a melanoma mutational landscape in the absence of UV light, where tumors manifest with remarkably low mutation burden and high heterogeneity. Genotype specific amplification of protein kinase A in cooperation with BRAF and p53 mutation suggests the involvement of melanogenesis in these tumors. This work is important for defining the spectrum of events in BRAF or NRAS driven melanoma in the absence of UV light, and for informed exploitation of models such as transgenic zebrafish to better understand mechanisms leading to human melanoma formation. C1 [Yen, Jennifer; Wedge, David C.; Van Loo, Peter; Jones, David; Raine, Keiran; Martincorena, Inigo; Nik-Zainal, Serena; Mudie, Laura; Marshall, John; Ramakrishna, Manasa; Tarpey, Patrick; Shlien, Adam; Whitmore, Ian; Gamble, Steve; Latimer, Calli; Menzies, Andy; McLaren, Stuart; O'Meara, Sarah; Butler, Adam; Teague, Jon; Campbell, Peter; Adams, David J.; Stemple, Derek L.; Futreal, P. Andy] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. [White, Richard M.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [White, Richard M.] Weill Cornell Med Coll, New York, NY 10065 USA. [Van Loo, Peter] VIB, Dept Human Genet, B-3000 Louvain, Belgium. [Van Loo, Peter] Univ Louvain, B-3000 Louvain, Belgium. [de Ridder, Jeroen] Delft Univ Technol, Delft Bioinformat Lab, NL-2628 CD Delft, Netherlands. [Capper, Amy; Richardson, Jennifer] MRC Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland. [Capper, Amy; Richardson, Jennifer] Edinburgh Canc Res Ctr, Edinburgh EH4 2XU, Midlothian, Scotland. [Watson, Ian R.; Wu, Chang-Jiun; Futreal, P. Andy] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77054 USA. [Cheng, Jiqiu; Moreau, Yves] Univ Louvain, Dept Elect Engn, B-3001 Heverlee, Belgium. [Langdon, Erin; Kaufman, Charles; Dovey, Mike; Taylor, Alison; Zon, Leonard I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Langdon, Erin; Kaufman, Charles; Dovey, Mike; Taylor, Alison; Zon, Leonard I.] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA 02115 USA. [Lister, James] Virginia Commonwealth Univ, Dept Human & Mol Genet, Richmond, VA 23298 USA. [Chin, Lynda] Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Houston, TX 77030 USA. RP Futreal, PA (reprint author), Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. EM afutreal@mdanderson.org RI Gamble, Stephen/D-1417-2011; OI Gamble, Stephen/0000-0002-0867-3723; Van Loo, Peter/0000-0003-0292-1949; Wedge, David/0000-0002-7572-3196 FU Wellcome Trust; Flanders Research Foundation (FWO); National Research Council; Cancer Research UK; NIH [K08AR61071]; MRC, AICR; FP7 ZF-CANCER FX We would like to thank Jared Simpson for running the SGA analysis and Bettina Fischer for help with the aCGH. This work was supported by the Wellcome Trust. PVL is supported by the Flanders Research Foundation (FWO); AS by a HL Holmes Award from the National Research Council; DJA by Cancer Research UK; CKK by NIH grant K08AR61071; and EEP by the MRC, AICR and FP7 ZF-CANCER. NR 61 TC 16 Z9 16 U1 1 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2013 VL 14 IS 10 AR R113 DI 10.1186/gb-2013-14-10-r113 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 285IN UT WOS:000329387500006 PM 24148783 ER PT B AU Bartlett, JD AF Bartlett, John D. BE Rawlings, ND Salvesen, GS TI Matrix Metalloproteinase-20/Enamelysin SO HANDBOOK OF PROTEOLYTIC ENZYMES, VOLS 1 AND 2, 3RD EDITION LA English DT Article; Book Chapter ID HYPOMATURATION AMELOGENESIS IMPERFECTA; CHROMOSOMAL LOCATION; TISSUE DISTRIBUTION; ODONTOGENIC-TUMORS; ENAMEL PROTEINASES; MOLECULAR-CLONING; MOUSE ENAMELYSIN; BOVINE ENAMEL; DENTAL ENAMEL; IN-VITRO C1 Forsyth Inst, Dept Cytokine Biol, Cambridge, MA 02142 USA. RP Bartlett, JD (reprint author), Forsyth Inst, Dept Cytokine Biol, 245 1st St, Cambridge, MA 02142 USA. EM jbartlett@forsyth.org NR 44 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-382220-8; 978-0-12-382219-2 PY 2013 BP 835 EP 840 DI 10.1016/B978-0-12-382219-2.00171-X PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJJ95 UT WOS:000328545101037 ER PT B AU Terada, S Fujimura, S AF Terada, Shigeyuki Fujimura, Satoshi BE Rawlings, ND Salvesen, GS TI Brevilysin H6 SO HANDBOOK OF PROTEOLYTIC ENZYMES, VOLS 1 AND 2, 3RD EDITION LA English DT Article; Book Chapter ID VENOM C1 [Terada, Shigeyuki] Fukuoka Univ, Dept Chem, Fac Sci, Fukuoka 8140180, Japan. [Fujimura, Satoshi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Immunobiol Lab, Charlestown, MA 02129 USA. RP Terada, S (reprint author), Fukuoka Univ, Dept Chem, Fac Sci, Fukuoka 8140180, Japan. EM sterada@fukuoka-u.ac.jp; satoshi.fujimura@cbrc2.mgh.harvard.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-382220-8; 978-0-12-382219-2 PY 2013 BP 964 EP 965 DI 10.1016/B978-0-12-382219-2.00201-5 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJJ95 UT WOS:000328545101067 ER PT B AU Park, E Yoo, SJ Seong, IS Goldberg, AL Chung, CH AF Park, Eunyong Yoo, Soon Ji Seong, Ihn Sik Goldberg, Alfred L. Chung, Chin Ha BE Rawlings, ND Salvesen, GS TI HslVU Protease SO HANDBOOK OF PROTEOLYTIC ENZYMES, VOLS 1 AND 2, 3RD EDITION LA English DT Article; Book Chapter ID ATP-DEPENDENT PROTEASE; HEAT-SHOCK GENES; CELL-DIVISION INHIBITOR; ESCHERICHIA-COLI; CLP PROTEASE; MOLECULAR CHARACTERIZATION; PROTEOLYTIC ACTIVITY; CRYSTAL-STRUCTURE; ABNORMAL PROTEIN; HSLUV PROTEASE C1 [Park, Eunyong; Chung, Chin Ha] Seoul Natl Univ, Sch Biol Sci, Seoul 151742, South Korea. [Yoo, Soon Ji] Kyung Hee Univ, Dept Biol, Seoul 130701, South Korea. [Seong, Ihn Sik] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Goldberg, Alfred L.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Park, E (reprint author), Seoul Natl Univ, Sch Biol Sci, Seoul 151742, South Korea. EM eunyongpark@gmail.com; yoosoonji@khu.ac.kr; iseong@chgr.mgh.harvard.edu; alfred_goldberg@hms.harvard.edu; chchung@snu.ac.kr NR 65 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-382220-8; 978-0-12-382219-2 PY 2013 BP 3677 EP 3683 DI 10.1016/B978-0-12-382219-2.00815-2 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJJ95 UT WOS:000328545105120 ER PT S AU Zhu, TF Budin, I Szostak, JW AF Zhu, Ting F. Budin, Itay Szostak, Jack W. BE Lorsch, J TI Preparation of Fatty Acid or Phospholipid Vesicles by Thin-film Rehydration SO LABORATORY METHODS IN ENZYMOLOGY: CELL, LIPID AND CARBOHYDRATE SE Methods in Enzymology LA English DT Review; Book Chapter AB Prepare polydisperse, multilamellar vesicles by rehydrating a thin film of fatty acids or phospholipids. C1 [Zhu, Ting F.; Budin, Itay; Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu FU Howard Hughes Medical Institute NR 4 TC 1 Z9 1 U1 3 U2 18 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-420067-8 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2013 VL 533 BP 267 EP 274 DI 10.1016/B978-0-12-420067-8.00020-9 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJN43 UT WOS:000329254800020 PM 24182932 ER PT S AU Zhu, TF Budin, I Szostak, JW AF Zhu, Ting F. Budin, Itay Szostak, Jack W. BE Lorsch, J TI Vesicle Extrusion Through Polycarbonate Track-etched Membranes using a Hand-held Mini-extruder SO LABORATORY METHODS IN ENZYMOLOGY: CELL, LIPID AND CARBOHYDRATE SE Methods in Enzymology LA English DT Review; Book Chapter AB The vesicle extrusion method is used for preparing small (e.g., 100 nm diameter) mono-disperse (uniform-sized) vesicles. Polycarbonate track-etched membranes with pores generally ranging from 50 to 200 nm in diameter and a hand-held mini-extruder are used for such a procedure. Extrusion through small (100 nm in diameter or smaller) pores also ensures that the vesicle population is predominantly unilamellar. C1 [Zhu, Ting F.; Budin, Itay; Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu FU Howard Hughes Medical Institute NR 3 TC 0 Z9 1 U1 1 U2 9 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-420067-8 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2013 VL 533 BP 275 EP 282 DI 10.1016/B978-0-12-420067-8.00021-0 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJN43 UT WOS:000329254800021 PM 24182933 ER PT S AU Zhu, TF Budin, I Szostak, JW AF Zhu, Ting F. Budin, Itay Szostak, Jack W. BE Lorsch, J TI Preparation of Fatty Acid Micelles SO LABORATORY METHODS IN ENZYMOLOGY: CELL, LIPID AND CARBOHYDRATE SE Methods in Enzymology LA English DT Review; Book Chapter ID GROWTH AB Here we describe a method for preparing fatty acid micelles. The method for adding micelles to a buffered solution containing fatty acid or phospholipid vesicles is also discussed. C1 [Zhu, Ting F.; Budin, Itay; Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu FU Howard Hughes Medical Institute NR 4 TC 2 Z9 2 U1 3 U2 12 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-420067-8 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2013 VL 533 BP 283 EP 288 DI 10.1016/B978-0-12-420067-8.00022-2 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BJN43 UT WOS:000329254800022 PM 24182934 ER PT J AU Caswell, JL Kerlikowske, K Shepherd, JA Cummings, SR Hu, DL Huntsman, S Ziv, E AF Caswell, Jennifer L. Kerlikowske, Karla Shepherd, John A. Cummings, Steven R. Hu, Donglei Huntsman, Scott Ziv, Elad TI High mammographic density in women of Ashkenazi Jewish descent SO BREAST CANCER RESEARCH LA English DT Article ID BREAST-CANCER RISK; X-RAY ABSORPTIOMETRY; EUROPEAN AMERICANS; DIGITAL MAMMOGRAMS; POPULATION HISTORY; MUTATION CARRIERS; FAMILY-HISTORY; UNITED-STATES; ASSOCIATION; HERITABILITY AB Introduction: Percent mammographic density (PMD) adjusted for age and body mass index is one of the strongest risk factors for breast cancer and is known to be approximately 60% heritable. Here we report a finding of an association between genetic ancestry and adjusted PMD. Methods: We selected self-identified Caucasian women in the California Pacific Medical Center Research Institute Cohort whose screening mammograms placed them in the top or bottom quintiles of age-adjusted and body mass index-adjusted PMD. Our final dataset included 474 women with the highest adjusted PMD and 469 with the lowest genotyped on the Illumina 1 M platform. Principal component analysis(PCA) and identity-by-descent analyses allowed us to infer the women's genetic ancestry and correlate it with adjusted PMD. Results: Women of Ashkenazi Jewish ancestry, as defined by the first principal component of PCA and identity-bydescent analyses, represented approximately 15% of the sample. Ashkenazi Jewish ancestry, defined by the first principal component of PCA, was associated with higher adjusted PMD(P = 0.004). Using multivariate regression to adjust for epidemiologic factors associated with PMD, including age at parity and use of postmenopausal hormone therapy, did not attenuate the association. Conclusions: Women of Ashkenazi Jewish ancestry, based on genetic analysis, are more likely to have high age-adjusted and body mass index-adjusted PMD. Ashkenazi Jews may have a unique set of genetic variants or environmental risk factors that increase mammographic density. C1 [Caswell, Jennifer L.; Hu, Donglei; Huntsman, Scott; Ziv, Elad] Univ Calif San Francisco, Dept Med, Helen Diller Family Comprehens Canc Ctr, Inst Human Genet,Div Gen Internal Med, San Francisco, CA 94143 USA. [Kerlikowske, Karla] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Med, Gen Internal Med Sect 111A1, San Francisco, CA 94121 USA. [Kerlikowske, Karla] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Dept Epidemiol & Biostat, Gen Internal Med Sect 111A1, San Francisco, CA 94121 USA. [Shepherd, John A.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, MRSC AC122, San Francisco, CA 94143 USA. [Cummings, Steven R.] Calif Pacific Med Ctr Res Inst, San Francisco Coordinating Ctr, San Francisco, CA 94107 USA. RP Ziv, E (reprint author), Univ Calif San Francisco, Dept Med, Helen Diller Family Comprehens Canc Ctr, Inst Human Genet,Div Gen Internal Med, 1450 3rd St, San Francisco, CA 94143 USA. EM elad.ziv@ucsf.edu RI Ziv, Elad/L-5396-2014; OI Caswell-Jin, Jennifer/0000-0002-5711-8355 FU National Institutes of Health [HHSN268200782096C, HHSN268201100011I]; NCI [U01CA63740] FX The authors are grateful to Alice Larocca and Viktoriya Kopvak for assistance with database management and for retrieving the samples. They are grateful to Noah Rosenberg, Doron Behar, and Karl Skorecki for helpful discussions about the results of the analysis. Genotyping was supported by the National Institutes of Health HHSN268200782096C and HHSN268201100011I, and was completed at the Johns Hopkins University Center for Inherited Disease Research. Support for analysis was provided by R01CA120120 and K24169004 to EZ. Support for sample collection was provided by the DaCosta International Fund for Prevention of Breast Cancer, the Eli Lilly Foundation, and the California Pacific Medical Center CRCLE Program. The San Francisco Mammography Registry is supported by an NCI-funded Breast Cancer Surveillance Consortium cooperative agreement (U01CA63740). NR 56 TC 2 Z9 2 U1 0 U2 1 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. PY 2013 VL 15 IS 3 AR R40 DI 10.1186/bcr3424 PG 9 WC Oncology SC Oncology GA 279CQ UT WOS:000328937600004 PM 23668689 ER PT J AU Hayden, MR Banks, WA Shah, GN Gu, Z Sowers, JR AF Hayden, M. R. Banks, W. A. Shah, G. N. Gu, Z. Sowers, J. R. TI Cardiorenal Metabolic Syndrome and Diabetic Cognopathy SO CARDIORENAL MEDICINE LA English DT Article DE Diabetic cognopathy; Alzheimer's disease; Type 2 diabetes mellitus; Ultrastructure; Remodeling; Neurovascular unit; Blood-brain barrier ID BLOOD-BRAIN-BARRIER; RENIN-ANGIOTENSIN SYSTEM; CALCIFIC UREMIC ARTERIOLOPATHY; CHRONIC KIDNEY-DISEASE; ALZHEIMERS-DISEASE; VASCULAR DEMENTIA; OXIDATIVE STRESS; COGNITIVE DYSFUNCTION; MELLITUS; PERICYTES AB The prevalence of the cardiorenal metabolic syndrome (CRS) is increasing in parallel with obesity, type 2 diabetes mellitus, Alzheimer's disease, and other forms of dementia. Along with metabolic, inflammatory, and immunological abnormalities, there is maladaptive structural remodeling of the heart, kidney, and brain. The term 'diabetic cognopathy' (DC) may be used when discussing functional and structural changes in the brain of the diabetic patient. DC likely represents an advanced form of these changes in the brain that evolve with increasing duration of the CRS and subsequent clinical diabetes. We posit that DC develops due to a convergence of aging, genetic and lifestyle abnormalities (overnutrition and lack of exercise), which result in multiple injurious metabolic and immunologic toxicities such as dysfunctional immune responses, oxidative stress, inflammation, insulin resistance, and dysglycemia (systemically and in the brain). These converging abnormalities may lead to endothelial blood-brain barrier tight junction/adherens junction (TJ/AJ) complex remodeling and microglia activation, which may result in neurodegeneration, impaired cognition, and dementia. Herein, we describe the brain ultrastructural changes evolving from a normal state to maladaptive remodeling in rodent models of CRS including microglia activation/polarization and attenuation and/or loss of the TJ/AJ complexes, pericytes and astrocytes of the neurovascular unit. Further, we discuss the potential relationship between these structural changes and the development of DC, potential therapeutic strategies, and future directions. (C) 2013 S. Karger AG, Basel C1 [Hayden, M. R.; Sowers, J. R.] Univ Missouri, Dept Internal Med, Div Endocrinol Diabet & Metab, Columbia, MO 65212 USA. [Hayden, M. R.; Gu, Z.; Sowers, J. R.] Univ Missouri, Diabet & Cardiovasc Res Lab, Columbia, MO 65212 USA. [Sowers, J. R.] Univ Missouri, Dept Med Pharmacol & Physiol, Columbia, MO 65212 USA. [Sowers, J. R.] Harry S Truman Mem Vet Hosp, Columbia, MO 65201 USA. [Banks, W. A.] Univ Washington, Dept Med, Div Geriatr Med, Vet Affairs Puget Sound Hlth Care Syst,Geriat Res, Seattle, WA USA. [Shah, G. N.] St Louis Univ, Dept Internal Med, Div Endocrinol, St Louis, MO 63103 USA. RP Hayden, MR (reprint author), Univ Missouri, D109 Diabet Ctr HSC,1 Hosp Dr, Columbia, MO 65212 USA. EM mrh29@usmo.com FU NIH [R01 HL73101-01A1, R01 HL107910-01]; Veterans Affairs Merit System [0018] FX The authors would like to acknowledge Tommi White, PhD, of the University of Missouri Electron Microscopic Core Facility, Columbia, Mo., USA, for preparing and staining the transmission electron microscopic images for viewing. We wish to acknowledge Brenda Hunter for her editorial assistance. The work presented is supported by the NIH (R01 HL73101-01A1 and R01 HL107910-01), Veterans Affairs Merit System 0018 (J.R. Sowers). NR 65 TC 4 Z9 4 U1 2 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1664-3828 EI 1664-5502 J9 CARDIORENAL MED JI CardioRenal Med. PY 2013 VL 3 IS 4 BP 265 EP 282 DI 10.1159/000357113 PG 18 WC Cardiac & Cardiovascular Systems; Urology & Nephrology SC Cardiovascular System & Cardiology; Urology & Nephrology GA 278UL UT WOS:000328915300007 PM 24474955 ER PT J AU Hunemohr, N Krauss, B Dinkel, J Gillmann, C Ackermann, B Jakel, O Greilich, S AF Huenemohr, Nora Krauss, Bernhard Dinkel, Julien Gillmann, Clarissa Ackermann, Benjamin Jaekel, Oliver Greilich, Steffen TI Ion range estimation by using dual energy computed tomography SO ZEITSCHRIFT FUR MEDIZINISCHE PHYSIK LA English DT Article DE Heavy ion therapy; proton therapy; dual energy CT; stopping powers; WEPL ID MONTE-CARLO SIMULATIONS; PROTON STOPPING POWER; CT NUMBERS; RADIOTHERAPY; TISSUE; CALIBRATION; MODEL; DOSIMETRY; SCANNER; SINGLE AB Inaccurate conversion of CT data to water-equivalent path length (WEPL) is one of the most important uncertainty sources in ion treatment planning. Dual energy CT (DECT) imaging might help to reduce CT number ambiguities with the additional information. In our study we scanned a series of materials (tissue substitutes, aluminum, PMMA, and other polymers) in the dual source scanner (Siemens Somatom Definition Flash). Based on the 80 kVp/140Sn kVp dual energy images, the electron densities rho(e) and effective atomic numbers Z(eff) were calculated. We introduced a new lookup table that translates the rho(e) to the WEPL. The WEPL residuals from the calibration were significantly reduced for the investigated tissue surrogates compared to the empirical Hounsfield-look-up table (single energy CT imaging) from (-1.0 +/- 1.8)% to (0.1 +/- 0.7)% and for non-tissue equivalent PMMA from -7.8% to -1.0%. To assess the benefit of the new DECT calibration, we conducted a treatment planning study for three different idealized cases based on tissue surrogates and PMMA. The DECT calibration yielded a significantly higher target coverage in tissue surrogates and phantom material (i.e. PMMA cylindo; mean target coverage improved from 62% to 98%). To verify the DECT calibration for real tissue, ion ranges through a frozen pig head were measured and compared to predictions calculated by the standard single energy CT calibration and the novel DECT calibration. By using this method, an improvement of ion range estimation from -2.1% water-equivalent thickness deviation (single energy CT) to 0.3% (DECT) was achieved. If one excludes raypaths located on the edge of the sample accompanied with high uncertainties, no significant difference could be observed. C1 [Huenemohr, Nora; Dinkel, Julien; Gillmann, Clarissa; Jaekel, Oliver; Greilich, Steffen] German Canc Res Ctr, D-69120 Heidelberg, Germany. [Krauss, Bernhard] Siemens AG, Imaging & Therapy, Forchheim, Germany. [Dinkel, Julien] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ackermann, Benjamin; Jaekel, Oliver] Heidelberg Ion Beam Therapy Ctr HIT, Heidelberg, Germany. [Gillmann, Clarissa; Jaekel, Oliver] Univ Heidelberg Hosp, Heidelberg, Germany. RP Hunemohr, N (reprint author), German Canc Res Ctr, Neuenheimer Feld 280, D-69120 Heidelberg, Germany. EM n.huenemohr@dkfz.de OI Greilich, Steffen/0000-0001-6237-7936 FU Helmholtz Association at DKFZ FX The authors should like to thank Marcus Winter (HIT) and Swantje Ecker (BIT) for their valuable assistance and comments for measurements and discussions. We also thank Martina Jochim (DKFZ) for the help with the CT scans and Martin Bar (Pathology University Heidelberg) for the kind help with the pig head. N. Hunemohr is funded by the PhD program of the Helmholtz Association at DKFZ. NR 29 TC 13 Z9 13 U1 1 U2 8 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0939-3889 J9 Z MED PHYS JI Z. Med. Phys. PY 2013 VL 23 IS 4 BP 300 EP 313 DI 10.1016/j.zemedi.2013.03.001 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 280ED UT WOS:000329010600006 PM 23597413 ER PT J AU Hussein, Z Hamdy, O Chia, YC Lim, SL Natkunam, SK Hussain, H Tan, MY Sulaiman, R Nisak, B Chee, WSS Marchetti, A Hegazi, RA Mechanick, JI AF Hussein, Zanariah Hamdy, Osama Chia, Yook Chin Lim, Shueh Lin Natkunam, Santha Kumari Hussain, Husni Tan, Ming Yeong Sulaiman, Ridzoni Nisak, Barakatun Chee, Winnie Siew Swee Marchetti, Albert Hegazi, Refaat A. Mechanick, Jeffrey I. TI Transcultural Diabetes Nutrition Algorithm: A Malaysian Application SO INTERNATIONAL JOURNAL OF ENDOCRINOLOGY LA English DT Review ID RANDOMIZED-CONTROLLED-TRIAL; BODY-MASS INDEX; WEIGHT-LOSS; GLYCEMIC CONTROL; HIGH PREVALENCE; REGISTRY 2009; OBESE WOMEN; TYPE-2; CARE; PREVENTION AB Glycemic control among patients with prediabetes and type 2 diabetesmellitus (T2D) in Malaysia is suboptimal, especially after the continuous worsening over the past decade. Improved glycemic control may be achieved through a comprehensive management strategy that includes medical nutrition therapy (MNT). Evidence-based recommendations for diabetes-specific therapeutic diets are available internationally. However, Asian patients with T2D, including Malaysians, have unique disease characteristics and risk factors, as well as cultural and lifestyle dissimilarities, which may render international guidelines and recommendations less applicable and/or difficult to implement. With these thoughts in mind, a transcultural Diabetes Nutrition Algorithm (tDNA) was developed by an international task force of diabetes and nutrition experts through the restructuring of international guidelines for the nutritional management of prediabetes and T2D to account for cultural differences in lifestyle, diet, and genetic factors. The initial evidence-based global tDNA template was designed for simplicity, flexibility, and cultural modification. This paper reports the Malaysian adaptation of the tDNA, which takes into account the epidemiologic, physiologic, cultural, and lifestyle factors unique to Malaysia, as well as the local guidelines recommendations. C1 [Hussein, Zanariah] Pusat Pentadbiran Kerajaan Persekutuan, Hosp Putrajaya, Dept Med, Putrajaya 62250, Malaysia. [Hamdy, Osama] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Chia, Yook Chin] Univ Malaya, Med Ctr, Dept Med, Kuala Lumpur, Malaysia. [Lim, Shueh Lin] Hosp Pulau Pinang, Dept Med, George Town, Malaysia. [Natkunam, Santha Kumari] Hosp Tengku Ampuan Rahimah, Dept Med, Selangor, Malaysia. [Hussain, Husni] Putrajaya Hlth Clin, Putrajaya, Malaysia. [Tan, Ming Yeong] Int Med Univ, Dept Hlth Care, Kuala Lumpur 57000, Malaysia. [Sulaiman, Ridzoni] Hosp Kuala Lumpur, Dept Dietet & Food Serv, Kuala Lumpur, Malaysia. [Nisak, Barakatun] Univ Putra Malaysia, Dept Nutr & Dietet, Serdang, Malaysia. [Chee, Winnie Siew Swee] Int Med Univ, Dept Nutr & Dietet, Kuala Lumpur 57000, Malaysia. [Marchetti, Albert] Univ Med & Dent New Jersey, Newark, NJ 07101 USA. [Hegazi, Refaat A.] Abbott Nutr, Columbus, OH 43219 USA. [Mechanick, Jeffrey I.] Icahn Sch Med Mt Sinai, Div Endocrinol Diabet & Bone Dis, New York, NY 10029 USA. RP Hussein, Z (reprint author), Pusat Pentadbiran Kerajaan Persekutuan, Hosp Putrajaya, Dept Med, Presint 7, Putrajaya 62250, Malaysia. EM zanariahh@hotmail.com RI CHIA, YOOK CHIN/B-8379-2010; Mohd Yusof, Barakatun Nisak/J-8414-2014 OI CHIA, YOOK CHIN/0000-0003-1995-0359; Mohd Yusof, Barakatun Nisak/0000-0003-0403-5895 FU Abbott Nutrition International FX The content of this paper was created and enriched solely by the authors, tDNA task force members, through a process of the ongoing literature searches, independent contributions and reviews, and group interactions for consensus. Financial support was provided by Abbott Nutrition International through an educational grant. Editorial support was provided by Mediconnexions Consulting Sdn Bhd. NR 49 TC 1 Z9 1 U1 0 U2 2 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-8337 EI 1687-8345 J9 INT J ENDOCRINOL JI Int. J. Endocrinol. PY 2013 AR 679396 DI 10.1155/2013/679396 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 277BF UT WOS:000328792700001 ER PT J AU Yu, MK Katon, W Young, BA AF Yu, Margaret K. Katon, Wayne Young, Bessie A. TI Diabetes Self-Care, Major Depression, and Chronic Kidney Disease in an Outpatient Diabetic Population SO NEPHRON CLINICAL PRACTICE LA English DT Article DE Chronic kidney disease; Depression; Diabetes mellitus; Self-care ID MEDICATION ADHERENCE; AFRICAN-AMERICANS; TYPE-2; PREVALENCE; MORTALITY; PATHWAYS; HOSPITALIZATION; METAANALYSIS; DIALYSIS; MELLITUS AB Background/Aims: The associations between major depression and chronic kidney disease (CKD) in patients with diabetes are incompletely characterized. Depressed patients with diabetes are known to have worse diabetes self-care, but it is not known whether this mediates the association between depression and CKD in this population. Methods: We conducted a cross-sectional study of the associations between major depressive symptoms and CKD in the Pathways Study (n = 4,082), an observational cohort of ambulatory diabetic patients from a managed care setting. Depression status was ascertained using the Patient Health Questionnaire-9 (PHQ-9). Stepwise logistic regression models examined the associations between depression and impaired estimated glomerular filtration rate (<60 ml/min/1.73 m(2)) or microalbuminuria, after adjustment for demographics, CKD risk factors, and diabetes self-care variables. Results: Clinically significant depression symptoms (PHQ-9 >= 10) were associated with a greater risk of microalbuminuria after adjustment for demographic variables (OR 1.54, 95% CI 1.21-1.95) and traditional CKD risk factors (OR 1.36, 95% CI 1.04-1.77); this association persisted after additional adjustment for diabetes self-care (OR 1.34, 95% CI 1.02-1.75). Depression was not associated with impaired estimated glomerular filtration rate in any of the models. Conclusion: In this cohort of diabetic subjects, clinically significant depression symptoms were associated with microalbuminuria, which could not be entirely explained by differences in diabetes self-care. (C) 2013 S. Karger AG, Basel C1 [Yu, Margaret K.; Young, Bessie A.] Univ Washington, Div Nephrol, Seattle, WA 98195 USA. [Yu, Margaret K.; Young, Bessie A.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Katon, Wayne] Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. [Young, Bessie A.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Yu, Margaret K.; Young, Bessie A.] Vet Affairs Puget Sound Hlth Care Syst, Kidney Res Inst, Seattle, WA USA. [Young, Bessie A.] Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA. RP Yu, MK (reprint author), Univ Washington, Box 356521,1959 NE Pacific St, Seattle, WA 98195 USA. EM mkyu@uw.edu FU National Institutes of Health [RO1 DK 079745, T32 DK007467, MH41739, MH01643]; American Kidney Fund Clinical Scientist in Nephrology Fellowship Program FX This study was supported by grants from the National Institutes of Health (RO1 DK 079745, T32 DK007467, MH41739, MH01643) and the American Kidney Fund Clinical Scientist in Nephrology Fellowship Program. We also thank Dr. Noel Weiss for reviewing the manuscript and the other investigators of the Pathways Study, without whom this research would not be possible. NR 33 TC 7 Z9 7 U1 7 U2 10 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2110 J9 NEPHRON CLIN PRACT JI Nephron. Clin. Pract. PY 2013 VL 124 IS 1-2 BP 106 EP 112 DI 10.1159/000355551 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 275UZ UT WOS:000328704800016 PM 24192760 ER PT J AU Grandpierre, A Chopra, D Doraiswamy, PM Tanzi, R Kafatos, MC AF Grandpierre, Attila Chopra, Deepak Doraiswamy, P. Murali Tanzi, Rudolph Kafatos, Menas C. TI A Multidisciplinary Approach to Mind and Consciousness SO NEUROQUANTOLOGY LA English DT Article DE genuine biological autonomy; decision making; quantitative aspects of consciousness; unconsciousness; self-consciousness; cells; universal mind ID QUANTUM-THEORY; UNIVERSE; MEMORY AB In the last 400 years physics has achieved great success, in theory and experimentation, determining the structure of matter and energy. The next great step in the evolution of science will be exploring the role of mind and consciousness in the universe, employing mathematics and fundamental theoretical constructs to yield specific predictions. Based on recent findings in biological autonomy, we propose to approach consciousness from the key aspect of decision-making. This approach allows us to develop a quantitative theory of consciousness as manifested in information processing. Since decision-making occurs at a certain level of organization, natural relations are obtained between consciousness at one level of organization and unconsciousness at another. By following this chain of argument, we also consider the possibility that levels of consciousness and unconsciousness form a self-closing hierarchy. This line of reasoning has led us to theoretically formulate the possible relationships between mind, cellular activity (both neuronal and non-neuronal), and the universe, working with the categories of consciousness, self-consciousness, and unconsciousness. What we propose in the present paper is a natural and straightforward extension of information theory to quantitative measures of consciousness at different levels and scales. A framework that integrates data from multiple disciplines can help us develop a broader theory of consciousness than what is possible from any single field alone. We present quantitative estimations for the rates of information processing at the global and cellular levels of the human organism and suggest values at the level of the universe. Our picture yields a new, quantitative picture of the mental capabilities of Homo sapiens and a reformulation of our place in the universe. C1 [Grandpierre, Attila; Kafatos, Menas C.] Chapman Univ, Schmid Coll Sci & Technol, Orange, CA 92866 USA. [Grandpierre, Attila] Hungarian Acad Sci, Konkoly Observ, H-1525 Budapest, Hungary. [Chopra, Deepak] Chopra Ctr, Carlsbad, CA USA. [Doraiswamy, P. Murali] Duke Univ, Med Ctr, Durham, NC USA. [Tanzi, Rudolph] Harvard Univ, Cambridge, MA 02138 USA. [Tanzi, Rudolph] Massachusetts Gen Hosp, Genet & Aging Res Unit, Boston, MA 02114 USA. RP Grandpierre, A (reprint author), Chapman Univ, Schmid Coll Sci & Technol, 1 Univ Dr, Orange, CA 92866 USA. EM grandp@iif.hu NR 39 TC 1 Z9 1 U1 2 U2 9 PU ANKA PUBLISHER PI BORNOVA PA 116-11 SOK NO.10 K 2 D 2, BORNOVA, IZMIR 35050, TURKEY SN 1303-5150 J9 NEUROQUANTOLOGY JI NeuroQuantology PY 2013 VL 11 IS 4 BP 607 EP 617 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 276HD UT WOS:000328739000012 ER PT J AU Lee, MS Freiberg, A Klauser, W Mow, CS Kim, SY AF Lee, Mel S. Freiberg, Andrew Klauser, Wolfgang Mow, Christopher S. Kim, Shin-Yoon TI Periprosthetic Joint Infection: Clinical and Bench SO SCIENTIFIC WORLD JOURNAL LA English DT Editorial Material C1 [Lee, Mel S.] Chang Gung Univ, Dept Orthopaed Surg, Chang Gung Mem Hosp, Linkou 333, Kweishan, Taiwan. [Freiberg, Andrew] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Klauser, Wolfgang] HELIOS ENDO Klin Hamburg, D-22767 Hamburg, Germany. [Mow, Christopher S.] Stanford Univ, Dept Orthopaed Surg, Med Ctr, Palo Alto, CA 94304 USA. [Kim, Shin-Yoon] Kyungpook Natl Univ, Skeletal Dis Genome Res Ctr, Dept Orthopaed Surg, Grad Sch Med, Taegu 702701, South Korea. RP Lee, MS (reprint author), Chang Gung Univ, Dept Orthopaed Surg, Chang Gung Mem Hosp, Linkou 333, Kweishan, Taiwan. EM mellee@adm.cgmh.org.tw OI Kim, Shin-Yoon/0000-0002-5445-648X NR 0 TC 0 Z9 0 U1 0 U2 2 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1537-744X J9 SCI WORLD J JI Sci. World J. PY 2013 AR 134786 DI 10.1155/2013/134786 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 279VK UT WOS:000328987300001 ER PT S AU Aganj, I Reuter, M Sabuncu, MR Fischl, B AF Aganj, Iman Reuter, Martin Sabuncu, Mert R. Fischl, Bruce GP IEEE TI SYMMETRIC NON-RIGID IMAGE REGISTRATION VIA AN ADAPTIVE QUASI-VOLUME-PRESERVING CONSTRAINT SO 2013 IEEE 10TH INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 10th International Symposium on Biomedical Imaging - From Nano to Macro (ISBI) CY APR 07-11, 2013 CL San Francisco, CA SP IEEE, IEEE Signal Processing Soc, Engn Med Biol Soc DE Non-rigid image registration; symmetry; inverse-consistency; volume-preserving constraints ID FREE-FORM DEFORMATION; BRAIN AB The standard implementation of non-rigid image registration is asymmetric, even though symmetry might be an intrinsic attribute of the particular application, e. g., pairwise image alignment. Current approaches to restore symmetry to non-rigid registration, although successful in achieving inverse-consistency, generally alter the objective function through implicit inclusion of a non-uniform weight in the integral that is computed on the native space of an input image. This inhomogeneous integral measure, which varies through the course of the registration, results in regional biases by allowing image regions to contribute differently to the objective function. In this work, instead of symmetrizing the objective function, we address the root of the problem: the non-uniformity of the integral in both the asymmetric and the symmetrized implementations. We introduce a new quasi-volume-preserving constraint that keeps the forward and backward objective functions arbitrarily close to each other - hence the registration symmetry - without compromising the uniformity of the integrals. We show the advantages of our method through experiments on synthetic images and real X-ray and MRI data. C1 [Aganj, Iman; Reuter, Martin; Sabuncu, Mert R.; Fischl, Bruce] Harvard Univ, Dept Elect Engn & Comp Sci, Massachusetts Gen Hosp, MIT,Martinos Ctr Biomedical Imaging,Sch Med, Cambridge, MA 02138 USA. RP Aganj, I (reprint author), Harvard Univ, Dept Elect Engn & Comp Sci, Massachusetts Gen Hosp, MIT,Martinos Ctr Biomedical Imaging,Sch Med, Cambridge, MA 02138 USA. RI Reuter, Martin/B-3456-2010 OI Reuter, Martin/0000-0002-2665-9693 NR 19 TC 1 Z9 1 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4673-6455-3 J9 I S BIOMED IMAGING PY 2013 BP 230 EP 233 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BHX19 UT WOS:000326900100058 ER PT S AU Luessi, M Hamalainen, MS Solo, V AF Luessi, Martin Haemaelaeinen, Matti S. Solo, Victor GP IEEE TI SPARSE COMPONENT SELECTION WITH APPLICATION TO MEG SOURCE LOCALIZATION SO 2013 IEEE 10TH INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 10th International Symposium on Biomedical Imaging - From Nano to Macro (ISBI) CY APR 07-11, 2013 CL San Francisco, CA SP IEEE, IEEE Signal Processing Soc, Engn Med Biol Soc DE minorization-maximization; penalized likelihood; sparsity; MEG; EEG; source localization ID APPROXIMATION; EM AB In several applications, the observed signal can be modeled as the projection of a sparse signal with constant support over time plus additive noise. In this paper, we develop a sparse component selection method which models the latent signal to be sparse and to be composed of a number unknown basis signals. The estimation is based on the maximization of the penalized log-likelihood, for which we develop an efficient minorization-maximization (MM) algorithm. We use simulations with synthetic data and real data from a magnetoencephalography (MEG) experiment to demonstrate the performance of the method. C1 [Luessi, Martin; Haemaelaeinen, Matti S.; Solo, Victor] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Luessi, M (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RI Hamalainen, Matti/C-8507-2013 NR 12 TC 1 Z9 1 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4673-6455-3 J9 I S BIOMED IMAGING PY 2013 BP 556 EP 559 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BHX19 UT WOS:000326900100139 ER PT S AU Hu, CH Cheng, L Sepulcre, J El Fakhri, G Lu, YM Li, QZ AF Hu, Chenhui Cheng, Lin Sepulcre, Jorge El Fakhri, Georges Lu, Yue M. Li, Quanzheng GP IEEE TI A GRAPH THEORETICAL REGRESSION MODEL FOR BRAIN CONNECTIVITY LEARNING OF ALZHEIMER'S DISEASE SO 2013 IEEE 10TH INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 10th International Symposium on Biomedical Imaging - From Nano to Macro (ISBI) CY APR 07-11, 2013 CL San Francisco, CA SP IEEE, IEEE Signal Processing Soc, Engn Med Biol Soc DE Graph regression; spectral graph theory; Laplacian; functional brain connectivity; Alzheimer's disease ID NETWORKS AB Learning functional brain connectivity is essential to the understanding of neurodegenerative diseases. In this paper, we introduce a novel graph regression model (GRM) which regards the imaging data as signals defined on a graph and optimizes the fitness between the graph and the data, with a sparsity level regularization. The proposed framework features a nice interpretation in terms of low-pass signals on graphs, and is more generic compared with the previous statistical models. Results based on the simulated data illustrates that our approach can obtain a very close reconstruction of the true network. We then apply the GRM to learn the brain connectivity of Alzheimer's disease (AD). Evaluations performed upon PET imaging data of 30 AD patients demonstrate that the connectivity patterns discovered are easy to interpret and consistent with known pathology. Index Terms-Graph regression, spectral graph theory, C1 [Hu, Chenhui; Lu, Yue M.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Hu, Chenhui; Sepulcre, Jorge; El Fakhri, Georges; Li, Quanzheng] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Boston, MA USA. [Cheng, Lin] Trinity Coll, Dept Engn, Hartford, CT USA. RP Hu, CH (reprint author), Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. FU NIH [R21CA149587, R01EB013293] FX This work was funded in part by NIH R21CA149587 and R01EB013293 NR 13 TC 7 Z9 7 U1 0 U2 3 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4673-6455-3 J9 I S BIOMED IMAGING PY 2013 BP 616 EP 619 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BHX19 UT WOS:000326900100154 ER PT S AU Dutta, J El Fakhri, G Huang, C Petibon, Y Reese, TG Li, QZ AF Dutta, Joyita El Fakhri, Georges Huang, Chuan Petibon, Yoann Reese, Timothy G. Li, Quanzheng GP IEEE TI RESPIRATORY MOTION COMPENSATION IN SIMULTANEOUS PET/MR USING A MAXIMUM A POSTERIORI APPROACH SO 2013 IEEE 10TH INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 10th International Symposium on Biomedical Imaging - From Nano to Macro (ISBI) CY APR 07-11, 2013 CL San Francisco, CA SP IEEE, IEEE Signal Processing Soc, Engn Med Biol Soc DE Motion compensation; multimodality imaging; image reconstruction; PET/MR ID IMAGE-RECONSTRUCTION; MRI AB The quantitative reliability of pulmonary PET scans is compromised by respiratory motion. The emergence of simultaneous, whole-body PET/MR imaging enables us to correct for motion artifacts in PET using motion information derived from anatomical MR images. We present here a framework for respiratory motion-compensated PET image reconstruction using simultaneous PET/MR. We have developed a radial FLASH pulse sequence for generating gated volumetric MR images at a reasonable speed without significantly sacrificing image quality. A navigator encapsulated within the pulse sequence enables us to retrospectively compute time bins corresponding to each gate. The deformation fields for each gate with respect to a reference gate are computed from the gated MR images by means of non-rigid registration. The gated MR images are also used to generate individual attenuation maps for each gate. Finally motion-compensated PET reconstruction is performed using a maximum a posteriori (MAP) approach. The complete framework was applied to a clinical study conducted on the Biograph mMR scanner (Siemens Medical Solutions), which allows simultaneous acquisition of whole-body PET/MR data. This study demonstrates the utility of our framework in generating meaningful estimates of deformation fields and correcting for motion artifacts in PET. C1 [Dutta, Joyita; El Fakhri, Georges; Huang, Chuan; Petibon, Yoann; Reese, Timothy G.; Li, Quanzheng] Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. RP Dutta, J (reprint author), Massachusetts Gen Hosp, Ctr Adv Med Imaging Sci, Boston, MA 02114 USA. NR 11 TC 8 Z9 8 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4673-6455-3 J9 I S BIOMED IMAGING PY 2013 BP 800 EP 803 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BHX19 UT WOS:000326900100200 ER PT S AU Ishaq, O Negri, J Bray, MA Pacureanu, A Peterson, RT Wahlby, C AF Ishaq, Omer Negri, Joseph Bray, Mark-Anthony Pacureanu, Alexandra Peterson, Randall T. Waehlby, Carolina GP IEEE TI AUTOMATED QUANTIFICATION OF ZEBRAFISH TAIL DEFORMATION FOR HIGH-THROUGHPUT DRUG SCREENING SO 2013 IEEE 10TH INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING (ISBI) SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT IEEE 10th International Symposium on Biomedical Imaging - From Nano to Macro (ISBI) CY APR 07-11, 2013 CL San Francisco, CA SP IEEE, IEEE Signal Processing Soc, Engn Med Biol Soc DE Curvature extraction; high-throughput screening; quantitative microscopy; zebrafish (Danio rerio) ID MODEL; CANCER AB Zebrafish (Danio rerio) is an important vertebrate model organism in biomedical research thanks to its ease of handling and translucent body, enabling in vivo imaging. Zebrafish embryos undergo spinal deformation upon exposure to chemical agents that inhibit DNA repair. Automated image-based quantification of spine deformation is therefore attractive for whole-organism based assays for use in early-phase drug discovery. We propose an automated method for accurate high-throughput measurement of tail deformations in multi-fish micro-plate wells. The method generates refined medial representations of partial tail-segments. Subsequently, these disjoint segments are analyzed and fused to generate complete tails. Based on estimated tail curvatures we reach a classification accuracy of 91% on individual animals as compared to known control treatment. This accuracy is increased to 95% when combining scores for fish in the same well. C1 [Ishaq, Omer; Pacureanu, Alexandra; Waehlby, Carolina] Uppsala Univ, Ctr Image Anal, SciLifeLab, Uppsala, Sweden. [Negri, Joseph; Bray, Mark-Anthony; Peterson, Randall T.; Waehlby, Carolina] Broad Inst Harvard, Cambridge, MA USA. [Negri, Joseph; Bray, Mark-Anthony; Peterson, Randall T.; Waehlby, Carolina] MIT, Cambridge, MA USA. [Peterson, Randall T.] Massachusetts Gen Hosp, Harvard Med Sch, Dept Med, Charlestown, MA USA. RP Ishaq, O (reprint author), Uppsala Univ, Ctr Image Anal, SciLifeLab, Uppsala, Sweden. FU NIH and SciLifLab Sweden [R01 GM095672] FX This work was supported in part by grant number R01 GM095672 from NIH and SciLifLab Sweden. NR 14 TC 2 Z9 2 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4673-6455-3 J9 I S BIOMED IMAGING PY 2013 BP 902 EP 905 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BHX19 UT WOS:000326900100226 ER PT J AU Schnieder, S Stappert, S Takahashi, M Fricchione, GL Esch, T Krajewski, J AF Schnieder, Sebastian Stappert, Sarah Takahashi, Masaya Fricchione, Gregory L. Esch, Tobias Krajewski, Jarek TI Sustainable Reduction of Sleepiness through Salutogenic Self-Care Procedure in Lunch Breaks: A Pilot Study SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Article ID PROGRESSIVE MUSCLE-RELAXATION; STRESS-MANAGEMENT INTERVENTION; QUALITY-OF-LIFE; PHYSICAL-ACTIVITY; CONTROLLED-TRIAL; NAP; METAANALYSIS; ASSOCIATION; ALERTNESS; CORTISOL AB The aim of the study was to elucidate the immediate, intermediate, and anticipatory sleepiness reducing effects of a salutogenic self-care procedure called progressive muscle relaxation (PMR), during lunch breaks. The second exploratory aim deals with determining the onset and long-term time course of sleepiness changes. In order to evaluate the intraday range and interday change of the proposed relaxation effects, 14 call center agents were assigned to either a daily 20-minute self-administered PMR or a small talk (ST) group during a period of seven months. Participants' levels of sleepiness were analyzed in a controlled trial using anticipatory, postlunchtime, and afternoon changes of sleepiness as indicated by continuously determined objective reaction time measures (16,464 measurements) and self-reports administered five times per day, once per month (490 measurements). Results indicate that, in comparison to ST, the PMR break (a) induces immediate, intermediate, and anticipatory reductions in sleepiness; (b) these significant effects remarkably show up after one month, and sleepiness continues to decrease for at least another five months. Although further research is required referring to the specific responsible mediating variables, our results suggest that relaxation based lunch breaks are both accepted by employees and provide a sustainable impact on sleepiness. C1 [Schnieder, Sebastian; Stappert, Sarah; Krajewski, Jarek] Univ Wuppertal, Schumpeter Sch Business & Econ, D-42119 Wuppertal, Germany. [Takahashi, Masaya] NIOSH, Tama Ku, Kawasaki, Kanagawa 2148585, Japan. [Fricchione, Gregory L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA. [Esch, Tobias] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Esch, Tobias] Coburg Univ Appl Sci, Div Integrat Hlth Promot, D-96450 Coburg, Germany. RP Schnieder, S (reprint author), Univ Wuppertal, Schumpeter Sch Business & Econ, Gaussstr 20, D-42119 Wuppertal, Germany. EM s.schnieder@uni-wuppertal.de RI Esch, Tobias/J-3812-2013 OI Esch, Tobias/0000-0001-5176-4367 FU German Research Foundation [KR3698/4-1] FX The authors would like to thank Aleksandra Makarova her for helpful feedback on our draft paper and Tom Laufenberg for his invaluable support. The work is partly funded by the German Research Foundation (KR3698/4-1). NR 46 TC 0 Z9 0 U1 0 U2 4 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1741-427X EI 1741-4288 J9 EVID-BASED COMPL ALT JI Evid.-based Complement Altern. Med. PY 2013 AR 387356 DI 10.1155/2013/387356 PG 10 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 271VU UT WOS:000328420500001 ER PT J AU Peterson, AL Murchison, C Zabetian, C Leverenz, JB Watson, GS Montine, T Carney, N Bowman, GL Edwards, K Quinn, JF AF Peterson, Amie L. Murchison, Charles Zabetian, Cyrus Leverenz, James B. Watson, G. Stennis Montine, Thomas Carney, Natasha Bowman, Gene L. Edwards, Karen Quinn, Joseph F. TI Memory, Mood, and Vitamin D in Persons with Parkinson's Disease SO JOURNAL OF PARKINSONS DISEASE LA English DT Article DE Parkinson's disease; vitamin D; dementia; depression; cognition ID MILD COGNITIVE IMPAIRMENT; SERUM 25-HYDROXYVITAMIN D; D SUPPLEMENTATION; DOUBLE-BLIND; D DEFICIENCY; POPULATION; DEPRESSION; PREVALENCE; DEMENTIA; BRAIN AB Background: Research in recent years has suggested a role of vitamin D in the central nervous system. The final converting enzyme and the vitamin D receptor are found throughout the human brain. From animal studies vitamin D appears important in neurodevelopment, up-regulation of neurotrophic factors, stabilization of mitochondrial function, and antioxidation. Objective: To examine the relationship between serum vitamin D and neuropsychiatric function in persons with Parkinson's disease (PD). Methods: This is an add-on study to a longitudinal study following neuropsychiatric function in persons with PD. Baseline neuropsychiatric performance and serum 25-hydroxyvitamin D were examined for 286 participants with PD. Measures of global cognitive function (MMSE, MOCA, Mattis Dementia Scale), verbal memory (Hopkins Verbal Learning Test), fluency (animals, vegetables, and FAS words), visuospatial function (Benton Line Orientation), executive function (Trails Making Test and Digit-Symbol Substitution), PD severity (Hoehn & Yahr and Unified Parkinson's Disease Rating Scale) and depression (Geriatric Depression Scale (GDS)) were administered. Multivariate linear regression assessed the association between vitaminD concentration and neuropsychiatric function, in the entire cohort as well as the non-demented and demented subsets. Results: Using a multivariate model, higher vitamin D concentrations were associated with better performance on numerous neuropsychiatric tests in the non-demented subset of the cohort. Significant associations were specifically found between vitamin D concentration and verbal fluency and verbal memory (t = 4.31, p < 0.001 and t = 3.04, p = 0.0083). Vitamin D concentrations also correlated with depression scores (t=-3.08, p = 0.0083) in the non-demented subset. Conclusions: Higher plasma vitamin D is associated with better cognition and better mood in this sample of PD patients without dementia. Determination of causation will require a vitamin D intervention study. C1 [Peterson, Amie L.; Carney, Natasha; Quinn, Joseph F.] Portland VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr PADRECC, Portland, OR USA. [Zabetian, Cyrus; Leverenz, James B.] VA Puget Sound Hlth Care Syst, Parkinsons Dis Res Educ & Clin Ctr PADRECC, Seattle, WA USA. [Zabetian, Cyrus; Leverenz, James B.; Watson, G. Stennis] VA Puget Sound Hlth Care Syst, Geriat Res Educ & Clin Ctr GRECC, Seattle, WA USA. [Leverenz, James B.] VA Puget Sound Hlth Care Syst, MIRECC, Seattle, WA USA. [Peterson, Amie L.; Murchison, Charles; Bowman, Gene L.; Quinn, Joseph F.] Oregon Hlth & Sci Univ, Portland, OR USA. [Zabetian, Cyrus; Leverenz, James B.; Watson, G. Stennis; Montine, Thomas; Edwards, Karen] Univ Washington, Seattle, WA 98195 USA. RP Peterson, AL (reprint author), Mail Code OP32,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM peterami@ohsu.edu OI Zabetian, Cyrus/0000-0002-7739-4306 FU Department of Veterans Affairs Office of Research and Development CDA2 Award - The Effects of Vitamin D on Balance in Parkinson's Disease; Parkinson Study Group; Parkinson's Disease Foundation's Advancing Parkinson's Treatments Innovations Grant; Pacific Northwest Udall Center [P50 NS062684]; Oregon Clinical and Translation Research Institute (OCTRI) from the National Center for Research Resources (NCRR) of the National Institutes of Health (NIH) [UL1 RR024140]; NIH Roadmap for Medical Research, NeuroNext [5U10NS077350-02]; NINDS [R01 NS065070]; Paul and Elizabeth Duffy Family Trust FX This research was made possible with support from the Department of Veterans Affairs Office of Research and Development CDA2 Award - The Effects of Vitamin D on Balance in Parkinson's Disease. Also from the Mentored Clinical Research Award Supported by the Parkinson Study Group and the Parkinson's Disease Foundation's Advancing Parkinson's Treatments Innovations Grant; the Pacific Northwest Udall Center (P50 NS062684); and the Oregon Clinical and Translation Research Institute (OCTRI), grant number UL1 RR024140 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research, NeuroNext (5U10NS077350-02) funded via NINDS, grant number R01 NS065070, and the Paul and Elizabeth Duffy Family Trust. NR 44 TC 10 Z9 12 U1 3 U2 11 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 2013 VL 3 IS 4 BP 547 EP 555 DI 10.3233/JPD-130206 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 270PY UT WOS:000328332100007 PM 24081441 ER PT B AU Dahlman, J Langer, R Goldberg, M AF Dahlman, James Langer, Robert Goldberg, Michael BE Peer, D TI Lipid-Like Delivery Materials for Efficient siRNA Delivery SO NANOTECHNOLOGY FOR THE DELIVERY OF THERAPEUTIC NUCLEIC ACIDS SE Pan Stanford Series on Biomedical Nanotechnology LA English DT Article; Book Chapter ID BREAST-CANCER METASTASIS; GENE DELIVERY; NONHUMAN-PRIMATES; CATIONIC LIPIDS; IMMUNE-SYSTEM; INFLAMMATION; MONOCYTES; LIBRARY; CELLS; MICE C1 [Dahlman, James; Langer, Robert] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Dahlman, James; Langer, Robert] MIT, David H Koch Ctr Integrat Canc Res, Cambridge, MA 02139 USA. [Goldberg, Michael] Dana Farber Canc Inst, Boston, MA 02215 USA. RP Dahlman, J (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM Michael_Goldberg1@dfci.harvard.edu NR 62 TC 0 Z9 0 U1 0 U2 1 PU PAN STANFORD PUBLISHING PTE LTD PI SINGAPORE PA PENTHOUSE LEVEL, SUNTEC TOWER 3, 8 TEMASEK BLVD, SINGAPORE, 038988, SINGAPORE BN 978-981-4411-05-9; 978-981-4411-04-2 J9 PAN ST SER BIOM NANO PY 2013 VL 4 BP 153 EP 177 D2 10.1201/b14773 PG 25 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA BJH13 UT WOS:000328155400008 ER PT J AU Lefkowitz, T Hazani, R Chowdhry, S Elston, J Yaremchuk, MJ Wilhelmi, BJ AF Lefkowitz, Todd Hazani, Ron Chowdhry, Saeed Elston, Josh Yaremchuk, Michael J. Wilhelmi, Bradon J. TI Anatomical Landmarks to Avoid Injury to the Great Auricular Nerve During Rhytidectomy SO AESTHETIC SURGERY JOURNAL LA English DT Article DE facelift; rhytidectomy; nerve damage; great auricular nerve; anatomic landmarks; SMAS ID PAROTIDECTOMY; SACRIFICE AB Background: An estimated 116 086 facelifts were performed in 2011. Regardless of the technique employed, facial flap elevation carries with it anatomical pitfalls of which any surgeon performing these procedures should be aware. Injury to the great auricular nerve (GAN) is the most common of these injuries, occurring at a rate of 60/0 to 7%. Objectives: We report our findings on the location of the GAN on the basis of anatomical landmarks to aid surgeons with planning their surgical approach for safe elevation of rhytidectomy skin flaps in the lateral neck region. Methods: Sixteen fresh cadaveric heads were dissected under loupe magnification. All specimens were dissected in a 45-degree (facelift) position in which a mid-sternocleidomastoid (SCM) incision was used for exposure. Measurements from the bony mastoid process, bony external auditory canal, external jugular vein, and anterior border of the SCM to the GAN were taken in each cadaver. Results: The GAN follows a consistent course over the mid-body of the SCM before bifurcating into anterior and posterior branches and terminal arborization. Regardless of the length of the SCM, the GAN at its most superficial location was found to be consistently at a ratio of one-third the distance from either the mastoid process or the external auditory canal to the clavicular origin of the SCM. Conclusions: Knowledge of the anatomy, course, and location of the GAN along the surface of SCM muscle based on anatomic landmarks and distance ratios can facilitate a safer dissection in the lateral neck during rhytidectomy procedures. C1 [Lefkowitz, Todd] Lenox Hill Hosp, Manhattan Eye Ear & Throat Hosp, New York, NY 10021 USA. [Yaremchuk, Michael J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Craniofacial Plast Surg, Boston, MA USA. [Chowdhry, Saeed; Elston, Josh; Wilhelmi, Bradon J.] Univ Louisville, Sch Med, Div Plast Surg, Louisville, KY 40292 USA. RP Wilhelmi, BJ (reprint author), Univ Louisville, Sch Med, Div Plast Surg, 550 S Jackson Str,ACB 2nd Floor, Louisville, KY 40292 USA. EM Bjwilh01@louisville.edu NR 9 TC 14 Z9 14 U1 0 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-820X EI 1527-330X J9 AESTHET SURG J JI Aesthet. Surg. J. PD JAN PY 2013 VL 33 IS 1 BP 19 EP 23 DI 10.1177/1090820X12469625 PG 5 WC Surgery SC Surgery GA 068VS UT WOS:000313394900002 PM 23277616 ER PT J AU Bai, LJ Harris, RE Kong, J Lao, LX Napadow, V Zhao, BX AF Bai, Lijun Harris, Richard E. Kong, Jian Lao, Lixing Napadow, Vitaly Zhao, Baixiao TI Neurobiological Mechanisms of Acupuncture SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Editorial Material C1 [Bai, Lijun] Xi An Jiao Tong Univ, Sch Life Sci & Technol, Key Lab Biomed Informat Engn, Minist Educ,Dept Biomed Engn, Xian 710049, Peoples R China. [Harris, Richard E.] Univ Michigan, Dept Anesthesiol, Ann Arbor, MI 48109 USA. [Kong, Jian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02129 USA. [Lao, Lixing] Univ Hong Kong, Sch Chinese Med, Pokfulam, Hong Kong, Peoples R China. [Napadow, Vitaly] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH HMS MIT Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Zhao, Baixiao] Beijing Univ Chinese Med, Sch Acupuncture Moxibust & Tuina, Beijing 100029, Peoples R China. RP Bai, LJ (reprint author), Xi An Jiao Tong Univ, Sch Life Sci & Technol, Key Lab Biomed Informat Engn, Minist Educ,Dept Biomed Engn, Xian 710049, Peoples R China. EM bailj4152615@gmail.com RI Bai, Lijun/C-5119-2015; OI Bai, Lijun/0000-0001-8790-5424; Lao, Lixing/0000-0003-0198-9714 NR 0 TC 0 Z9 0 U1 0 U2 5 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1741-427X EI 1741-4288 J9 EVID-BASED COMPL ALT JI Evid.-based Complement Altern. Med. PY 2013 AR 652457 DI 10.1155/2013/652457 PG 2 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 266JQ UT WOS:000328020300001 ER PT J AU Montano, CM Irizarry, RA Kaufmann, WE Talbot, K Gur, RE Feinberg, AP Taub, MA AF Montano, Carolina M. Irizarry, Rafael A. Kaufmann, Walter E. Talbot, Konrad Gur, Raquel E. Feinberg, Andrew P. Taub, Margaret A. TI Measuring cell-type specific differential methylation in human brain tissue SO GENOME BIOLOGY LA English DT Article DE DNA methylation; epigenetics; differentially methylated region; brain region; cell-type heterogeneity; deconvolution; NeuN; neuron; glia; postmortem brain; fluorescence activated cell sorting ID DNA-METHYLATION; GENE-EXPRESSION; HYPERMETHYLATION; HETEROGENEITY; PLASTICITY; NEURONS; ARRAYS AB The behavior of epigenetic mechanisms in the brain is obscured by tissue heterogeneity and disease-related histological changes. Not accounting for these confounders leads to biased results. We develop a statistical methodology that estimates and adjusts for celltype composition by decomposing neuronal and non-neuronal differential signal. This method provides a conceptual framework for deconvolving heterogeneous epigenetic data from postmortem brain studies. We apply it to find cell-specific differentially methylated regions between prefrontal cortex and hippocampus. We demonstrate the utility of the method on both Infinium 450k and CHARM data. C1 [Montano, Carolina M.] Johns Hopkins Univ, Sch Med, Med Scientist Training Program, Baltimore, MD 21205 USA. [Montano, Carolina M.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Predoctoral Training Program Human Genet, Baltimore, MD 21205 USA. [Irizarry, Rafael A.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Kaufmann, Walter E.] Boston Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. [Kaufmann, Walter E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Talbot, Konrad; Gur, Raquel E.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Feinberg, Andrew P.] Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD 21205 USA. [Taub, Margaret A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. RP Taub, MA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, 615 N Wolfe St, Baltimore, MD 21205 USA. EM mtaub@jhsph.edu FU NIH [U01 MH085270, R01 GM083084]; Department of Defense (CDMRP) [AR080125]; NIAMS [P30AR053503] FX All samples were obtained from the bank of the Center for Neurodegenerative Disease Research (CNDR) in the Department of Pathology and Laboratory Medicine at the University of Pennsylvania (directed by Dr John Q Trojanowski). This work was funded by NIH Grant U01 MH085270 to APF and CMM, Department of Defense (CDMRP) AR080125 to APF and WEK, and NIH Grant R01 GM083084 to RAI and MAT. The research reported in this publication was also supported by NIAMS Award Number P30AR053503. We would like to thank Joe Chrest for his expertise in cell sorting, Rakel Tryggvadottir for her assistance with sample hybridizations, and Romeo Papazyan for his help with fluorescence microscopy imaging. NR 34 TC 29 Z9 29 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PY 2013 VL 14 IS 8 AR R94 DI 10.1186/gb-2013-14-8-r94 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 268UF UT WOS:000328195400012 PM 24000956 ER PT S AU Ren, H Zhang, QX Qie, L Baker, GL AF Ren, Hong Zhang, Quanxuan Qie, Liangyi Baker, Gregory L. BE Doong, RA Sharma, VK Kim, H TI The Adjuvant Effect of Emerging Nanomaterials: A Double-Edged Sword SO INTERACTIONS OF NANOMATERIALS WITH EMERGING ENVIRONMENTAL CONTAMINANTS SE ACS Symposium Series LA English DT Proceedings Paper CT 244th National Fall Meeting of the American-Chemical-Society (ACS) CY AUG 19-23, 2012 CL Philadelphia, PA SP Amer Chem Soc, Div Hist Chem, Amer Chem Soc, Amer Chem Soc, Div Chem Educ, Amer Chem Soc, Div Inorgan Chem, Soc Biol Inorgan Chem, Amer Chem Soc, Div Polymer Chem Inc ID ALUMINUM-OXIDE NANOPARTICLES; MESOPOROUS SILICA SBA-15; IMMUNE-RESPONSE; GOLD NANOPARTICLES; AIR-POLLUTION; THERMORESPONSIVE POLYMER; N-ISOPROPYLACRYLAMIDE; PARTICULATE ANTIGENS; LUNG INFLAMMATION; ANTIBODY-RESPONSE AB Nanoparticles have growing applications in industry, consumer products, biology and medicine. One of those applications involves the interaction between nanoparticles and immune components. The nanoparticles can act as antigen carriers to deliver and release antigens to specific targets, and enhance the immune response against a variety of antigens as adjuvants. The adjuvant effects of nanoparticle size, shape, surface charge, linkage method on the immunological response are also discussed. In contrast, as-prepared nanomaterials and ambient particulate matter (PM) from air pollution exhibit adverse adjuvant effect in vitro and in vivo, and recent advances to address their potential risk on human health are also included in this review. C1 [Ren, Hong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr,Dept Radiol, Charlestown, MA 02129 USA. RP Ren, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr,Dept Radiol, Charlestown, MA 02129 USA. EM zhangqua@msu.edu RI Ren, Hong/J-5191-2015 OI Ren, Hong/0000-0003-0375-0360 NR 86 TC 2 Z9 2 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 978-0-8412-2916-7 J9 ACS SYM SER JI ACS Symp. Ser. PY 2013 VL 1150 BP 3 EP 21 PG 19 WC Chemistry, Physical; Engineering, Environmental; Materials Science, Multidisciplinary SC Chemistry; Engineering; Materials Science GA BJH29 UT WOS:000328178900002 ER PT J AU Suenaga, M Yamada, S Fujii, T Fuchs, BC Okumura, N Kanda, M Kobayashi, D Tanaka, C Nakayama, G Sugimoto, H Koike, M Nomoto, S Fujiwara, M Takeda, S Hayashi, K Tanabe, KK Goto, H Kodera, Y AF Suenaga, Masaya Yamada, Suguru Fujii, Tsutomu Fuchs, Bryan C. Okumura, Norio Kanda, Mitsuro Kobayashi, Daisuke Tanaka, Chie Nakayama, Goro Sugimoto, Hiroyuki Koike, Masahiko Nomoto, Shuji Fujiwara, Michitaka Takeda, Shin Hayashi, Kazuhiko Tanabe, Kenneth K. Goto, Hidemi Kodera, Yasuhiro TI A functional polymorphism in the epidermal growth factor gene predicts hepatocellular carcinoma risk in Japanese hepatitis C patients SO ONCOTARGETS AND THERAPY LA English DT Article DE epidermal growth factor; functional polymorphism; hepatocellular carcinoma; hepatitis C; hepatocarcinogenesis ID CHINESE PATIENTS; VIRUS-INFECTION; LIVER-DISEASE; ASSOCIATION; EXPRESSION; EGF; SUSCEPTIBILITY; CIRRHOSIS; RECEPTOR; LOCUS AB Background: A single nucleotide polymorphism (SNP) in the epidermal growth factor (EGF) gene (rs4444903) has been associated with increased risk of cancer, including hepatocellular carcinoma (HCC). The aim of this study was to examine the relationship between the EGF SNP genotype and the development and prognosis of HCC, in a Japanese population. Methods: Restriction fragment-length polymorphism was used to determine the presence of the EGF SNP genotype in 498 patients, including 208 patients with HCC. The level of EGF messenger ribonucleic acid (mRNA) expression in cancerous tissues was measured by quantitative reverse transcription polymerase chain reaction. The correlation between the EGF SNP genotype and prognosis was statistically analyzed in the patients with HCC. Results: The proportion of the A/A, A/G, and G/G genotypes were 5.3%, 42.8%, and 51.9%, respectively, in the patients with HCC, whereas in those without HCC, they were 8.6%, 35.9%, and 55.5%, respectively, revealing that the odds ratio (OR) of developing HCC was higher in patients with a G allele (OR = 1.94, P=0.080 for A/G patients and OR = 1.52, P=0.261 for G/G patients, as compared with A/A patients). In particular, when the analysis was limited to the 363 patients with hepatitis C, the OR for developing HCC was 3.54 (P=0.014) for A/G patients and was 2.85 (P=0.042) for G/G patients, as compared with A/A patients. Tumoral EGF mRNA expression in G/G patients was significantly higher than that in A/A patients (P=0.033). No statistically significant differences were observed between the EGF SNP genotype and disease-free or overall survival. Conclusion: The EGF SNP genotype might be associated with a risk for the development of HCC in Japanese patients but not with prognosis. Of note, the association is significantly stronger in patients with hepatitis C, which is the main risk factor for HCC in Japan. C1 [Suenaga, Masaya; Yamada, Suguru; Fujii, Tsutomu; Okumura, Norio; Kanda, Mitsuro; Kobayashi, Daisuke; Tanaka, Chie; Nakayama, Goro; Sugimoto, Hiroyuki; Koike, Masahiko; Nomoto, Shuji; Fujiwara, Michitaka; Kodera, Yasuhiro] Nagoya Univ, Grad Sch Med, Dept Gastroenterol Surg Surg 2, Nagoya, Aichi 4668550, Japan. [Fuchs, Bryan C.; Tanabe, Kenneth K.] Massachusetts Gen Hosp, Ctr Canc, Div Surg Oncol, Boston, MA USA. [Fuchs, Bryan C.; Tanabe, Kenneth K.] Harvard Univ, Sch Med, Boston, MA USA. [Takeda, Shin] Nagoya Med Ctr, Div Surg, Nagoya, Aichi, Japan. [Hayashi, Kazuhiko; Goto, Hidemi] Nagoya Univ, Grad Sch Med, Dept Gastroenterol, Nagoya, Aichi 4668550, Japan. RP Yamada, S (reprint author), Nagoya Univ, Grad Sch Med, Dept Gastroenterol Surg Surg 2, Showa Ku, 65 Tsurumai Cho, Nagoya, Aichi 4668550, Japan. EM suguru@med.nagoya-u.ac.jp RI Koike, Masahiko/M-4913-2014; Kodera, Yasuhiro/M-4912-2014; Kobayashi, Daisuke/M-4910-2014; tanaka, chie/M-5052-2014; Fujii, Tsutomu/M-4838-2014; HAYASHI, Kazuhiko/I-7382-2014; Kanda, Mitsuro/M-4891-2014 OI HAYASHI, Kazuhiko/0000-0002-7919-6071; NR 35 TC 7 Z9 9 U1 0 U2 2 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-6930 J9 ONCOTARGETS THER JI OncoTargets Ther. PY 2013 VL 6 BP 1805 EP 1812 DI 10.2147/OTT.S53625 PG 8 WC Biotechnology & Applied Microbiology; Oncology SC Biotechnology & Applied Microbiology; Oncology GA 269CT UT WOS:000328218900001 PM 24363559 ER PT J AU Wildgruber, M Swirski, FK Zernecke, A AF Wildgruber, Moritz Swirski, Filip K. Zernecke, Alma TI Molecular Imaging of Inflammation in Atherosclerosis SO THERANOSTICS LA English DT Review DE Molecular imaging; Inflammation; Atherosclerosis ID POSITRON-EMISSION-TOMOGRAPHY; CELL-ADHESION MOLECULE-1; OPTICAL COHERENCE TOMOGRAPHY; RAY COMPUTED-TOMOGRAPHY; ULTRASMALL SUPERPARAMAGNETIC PARTICLES; RISK-ASSESSMENT STRATEGIES; PORCINE CORONARY-ARTERIES; RESONANCE CONTRAST AGENT; RADIOLABELED ANNEXIN A5; MACROPHAGES IN-VIVO AB Acute rupture of vulnerable plaques frequently leads to myocardial infarction and stroke. Within the last decades, several cellular and molecular players have been identified that promote atherosclerotic lesion formation, maturation and plaque rupture. It is now widely recognized that inflammation of the vessel wall and distinct leukocyte subsets are involved throughout all phases of atherosclerotic lesion development. The mechanisms that render a stable plaque unstable and prone to rupture, however, remain unknown and the identification of the vulnerable plaque remains a major challenge in cardiovascular medicine. Imaging technologies used in the clinic offer minimal information about the underlying biology and potential risk for rupture. New imaging technologies are therefore being developed, and in the preclinical setting have enabled new and dynamic insights into the vessel wall for a better understanding of this complex disease. Molecular imaging has the potential to track biological processes, such as the activity of cellular and molecular biomarkers in vivo and over time. Similarly, novel imaging technologies specifically detect effects of therapies that aim to stabilize vulnerable plaques and silence vascular inflammation. Here we will review the potential of established and new molecular imaging technologies in the setting of atherosclerosis, and discuss the cumbersome steps required for translating molecular imaging approaches into the clinic. C1 [Wildgruber, Moritz] Tech Univ Munich, Klinikum Rechts Isar, Dept Radiol, D-81675 Munich, Germany. [Swirski, Filip K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA. [Zernecke, Alma] Tech Univ Munich, Klinikum Rechts Isar, Dept Vasc Surg, D-81675 Munich, Germany. [Zernecke, Alma] German Res Ctr Cardiovasc Res, Deutsch Zentrum Herz Kreislauf Forsch, Partner Site Munich Heart Alliance, Munich, Germany. RP Wildgruber, M (reprint author), Tech Univ Munich, Klinikum Rechts Isar, Dept Radiol, Ismaninger Str 22, D-81675 Munich, Germany. EM moritz.wildgruber@tum.de; zernecke@lrz.tum.de NR 183 TC 25 Z9 28 U1 4 U2 27 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2013 VL 3 IS 11 BP 865 EP 884 DI 10.7150/thno.5771 PG 20 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 268HX UT WOS:000328162100005 PM 24312156 ER PT J AU Alge, JL Karakala, N Neely, BA Janech, MG Velez, JCQ Arthur, JM AF Alge, Joseph L. Karakala, Nithin Neely, Benjamin A. Janech, Michael G. Velez, Juan Carlos Q. Arthur, John M. CA SAKInet Investigators TI Urinary angiotensinogen predicts adverse outcomes among acute kidney injury patients in the intensive care unit SO CRITICAL CARE LA English DT Article ID GELATINASE-ASSOCIATED LIPOCALIN; CRITICALLY-ILL PATIENTS; ACUTE-RENAL-FAILURE; FRACTIONAL EXCRETION; CARDIAC-SURGERY; AKI DIAGNOSIS; BIOMARKERS; RISK; UREA; DEFINITION AB Introduction: Acute kidney injury (AKI) is commonly observed in the intensive care unit (ICU), where it can be caused by a variety of factors. The objective of this study was to evaluate the prognostic value of urinary angiotensinogen, a candidate prognostic AKI biomarker identified in post-cardiac surgery patients, in this heterogeneous population. Methods: Urinary angiotensinogen was measured by ELISA and corrected for urine creatinine in 45 patients who developed AKI in the ICU. Patients were grouped by AKI etiology, and the angiotensinogen-to-creatinine ratio (uAnCR) was compared among the groups using the Kruskal-Wallis test. The ability of uAnCR to predict the following endpoints was tested using the area under the ROC curve (AUC): the need for renal replacement therapy (RRT) or death, increased length of stay (defined as hospital discharge > 7 days or death <= 7 days from sample collection), and worsening AKI (defined as an increase in serum creatinine > 0.3 mg/dL after sample collection or RRT). Results: uAnCR was significantly elevated in patients who met the composite outcome RRT or death (89.4 vs 25.4 ng/mg; P = 0.01), and it was a strong predictor of this outcome (AUC = 0.73). Patients with uAnCR values above the median for the cohort (55.21 ng/mg) had increased length of stay compared to patients with uAnCR = 55.21 ng/mg (22 days vs 7 days after sample collection; P = 0.01). uAnCR was predictive of the outcome increased length of stay (AUC = 0.77). uAnCR was also a strong predictor of worsening of AKI (AUC = 0.77). The uAnCR of patients with pre-renal AKI was lower compared to patients with AKI of other causes (median uAnCR 11.3 vs 80.2 ng/mg; P = 0.02). Conclusions: Elevated urinary angiotensinogen is associated with adverse events in AKI patients in the ICU. It could be used to identify high risk patients who would benefit from timely intervention that could improve their outcomes. C1 [Alge, Joseph L.; Karakala, Nithin; Neely, Benjamin A.; Janech, Michael G.; Velez, Juan Carlos Q.; Arthur, John M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Arthur, John M.] Ralph H Johnson VA Med Ctr, Med Serv, Charleston, SC 29401 USA. RP Arthur, JM (reprint author), Med Univ S Carolina, Dept Med, 96 Jonathan Lucas St, Charleston, SC 29425 USA. EM arthurj@musc.edu RI Velez, Juan Carlos/N-3782-2016; OI Neely, Benjamin/0000-0001-6120-7695; Alge, Joseph/0000-0002-2491-1066; Janech, Michael/0000-0002-3202-4811 FU NIH [R01 DK080234, UL1 RR029882]; Merit Review award from the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs FX This study was supported by NIH grant numbers R01 DK080234 and UL1 RR029882 and by a Merit Review award from the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs. The contents do not necessarily represent the views of the Department of Veterans Affairs or the United States Government. NR 32 TC 8 Z9 8 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X EI 1364-8535 J9 CRIT CARE JI Crit. Care PY 2013 VL 17 IS 2 AR R69 DI 10.1186/cc12612 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 264OG UT WOS:000327887300034 PM 23587112 ER PT J AU Cruzat, A Tauber, A Shukla, A Paschalis, EI Pineda, R Dohlman, CH AF Cruzat, Andrea Tauber, Allyson Shukla, Anita Paschalis, Eleftherios I. Pineda, Roberto Dohlman, Claes H. TI Low-Cost and Readily Available Tissue Carriers for the Boston Keratoprosthesis: A Review of Possibilities SO JOURNAL OF OPHTHALMOLOGY LA English DT Review ID CORNEAL REPLACEMENT; RABBIT MODEL; TRANSPLANTATION; KERATOPLASTY; EXPERIENCE; CARTILAGE AB The Boston keratoprosthesis (B-KPro), currently the most commonly used artificial cornea worldwide, can provide rapid visual rehabilitation for eyes with severe corneal opacities not suitable for standard corneal transplantation. However, the B-KPro presently needs a corneal graft as a tissue carrier. Although corneal allograft tissue is readily available in the United States and other developed countries with established eye banks, the worldwide need vastly exceeds supply. Therefore, a simple, safe, and inexpensive alternative to corneal allografts is desirable for the developing world. We are currently exploring reasonable alternative options such as corneal autografts, xenografts, noncorneal autologous tissues, and laboratory-made tissue constructs, as well as modifications to corneal allografts, such as deep-freezing, glycerol-dehydration, gamma irradiation, and cross-linking. These alternative tissue carriers for the B-KPro are discussed with special regard to safety, practicality, and cost for the developing world. C1 [Cruzat, Andrea; Tauber, Allyson; Shukla, Anita; Paschalis, Eleftherios I.; Pineda, Roberto; Dohlman, Claes H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea & Refract Surg Serv,Dept Ophthalmol, Boston, MA 02114 USA. RP Cruzat, A (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea & Refract Surg Serv,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM andreacruzat@gmail.com OI Paschalis, Eleftherios/0000-0002-4544-4452 NR 26 TC 4 Z9 4 U1 0 U2 4 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-004X EI 2090-0058 J9 J OPHTHALMOL JI J. Ophthalmol. PY 2013 AR 686587 DI 10.1155/2013/686587 PG 5 WC Medicine, Research & Experimental; Ophthalmology SC Research & Experimental Medicine; Ophthalmology GA 265NI UT WOS:000327958400001 ER PT J AU Ibanez, GE Levi-Minzi, MA Rigg, KK Mooss, AD AF Ibanez, Gladys E. Levi-Minzi, Maria A. Rigg, Khary K. Mooss, Angela D. TI Diversion of Benzodiazepines Through Healthcare Sources SO JOURNAL OF PSYCHOACTIVE DRUGS LA English DT Article DE benzodiazepines; dependence; diversion; prescription drug ID PRESCRIPTION OPIOID ABUSE; METHADONE-MAINTENANCE TREATMENT; NONMEDICAL USE; DRUG-ABUSE AB Benzodiazepines (BZ) are often diverted from legal sources to illicit markets at various points in the distribution process beginning with a pharmaceutical manufacturer, followed by healthcare providers, and finally, to the intended users. Little is known about the extent of BZ diversion involving distribution points directly related to healthcare sources versus points further down the distribution chain. The present study examines the scope of BZ diversion, and the association between BZ dependence and the direct utilization of particular healthcare-related diversion sources among a diverse sample of prescription drug abusers in South Florida. Cross-sectional data were collected from five different groups of drug users: methadone-maintenance clients (n = 247), street drug users (n = 238), public-pay treatment clients (n = 245), private-pay treatment clients (n = 228), and stimulant-using men who have sex with men (MSM; n = 249). Findings suggest that those who are ages 26 to 35 years old, non-Hispanic White participants, private-pay treatment clients, those who are insured, and those with higher incomes had higher odds of utilizing healthcare diversion sources. Those who reported BZ dependence had 2.5 times greater odds of using a healthcare source to obtain BZs than those who did not meet criteria for dependence. C1 [Ibanez, Gladys E.; Mooss, Angela D.] Behav Sci Res Inst, Coral Gables, FL USA. [Levi-Minzi, Maria A.] Nova SE Univ, Ctr Appl Res Subst Use & Hlth Dispar, Miami, FL 33137 USA. [Rigg, Khary K.] Philadelphia VA Med Ctr, Ctr Hlth Equi Res & Promot, Philadelphia, PA USA. RP Levi-Minzi, MA (reprint author), Nova SE Univ, 2 NE 40th St,Suite 404, Miami, FL 33137 USA. EM ms2007@nova.edu FU NIDA NIH HHS [R01 DA021330] NR 32 TC 5 Z9 5 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0279-1072 EI 2159-9777 J9 J PSYCHOACTIVE DRUGS JI J. Psychoact. Drugs PD JAN-MAR PY 2013 VL 45 IS 1 BP 48 EP 56 DI 10.1080/02791072.2013.764232 PG 9 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 265HN UT WOS:000327941300006 PM 23662331 ER PT J AU Crytzer, TM Dicianno, BE Fairman, AD AF Crytzer, Theresa M. Dicianno, Brad E. Fairman, Andrea D. TI Effectiveness of an Upper Extremity Exercise Device and Text Message Reminders to Exercise in Adults with Spina Bifida: A Pilot Study SO ASSISTIVE TECHNOLOGY LA English DT Article DE arm ergometry; cognition; exercise; exercise test; hydrocephalus; myelomeningocele; physical activity; spina bifida; upper extremity ID QUALITY-OF-LIFE; EVERYDAY PHYSICAL-ACTIVITY; YOUNG-ADULTS; CEREBRAL-PALSY; METABOLIC SYNDROME; CORD DYSFUNCTION; AEROBIC FITNESS; POCKET-COMPUTER; GMFCS LEVEL; HEALTH-CARE AB Obesity, deconditioning, cognitive impairment, and poor exercise tolerance are health issues concerning adults with spina bifida (SB). Our aim is to describe exercise participation and identify motivating tactics and exercise devices that increase participation. In a quasi-experimental randomized crossover design, the GameCycle was compared to a Saratoga Silver I arm ergometer. Personalized free or low-cost text/voice message reminders to exercise were sent. Nineteen young adults with SB were assigned to either the GameCycle or Saratoga exercise group. Within each group, participants were randomized to receive reminders to exercise, or no reminders, then crossed over to the opposite message group after eight weeks. Before and after a 16-week exercise program anthropometric, metabolic, exercise testing and questionnaire data, and recorded participation were collected. Miles traveled by the GameCycle group were significantly higher than the Saratoga exercise groups. No significant differences were found in participation between the message reminder groups. Low participation rates were seen overall. Those using the GameCycle traveled more miles. Barriers to exercise participation may have superseded ability to motivate adults with SB to exercise even with electronic reminders. Support from therapists to combat deconditioning and develop coping skills may be needed. C1 [Crytzer, Theresa M.; Dicianno, Brad E.] Vet Affairs Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. [Crytzer, Theresa M.; Dicianno, Brad E.; Fairman, Andrea D.] Univ Pittsburgh, Sch Hlth & Rehabil Sci, Pittsburgh, PA USA. [Dicianno, Brad E.] Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Fairman, Andrea D.] Philadelphia Univ, Dept Occupat Therapy, Philadelphia, PA USA. RP Dicianno, BE (reprint author), Kaufmann Med Bldg,3471 5th Ave, Pittsburgh, PA 15213 USA. EM dicianno@pitt.edu FU NICHD NIH HHS [T32 HD049307, T32HD049307] NR 78 TC 1 Z9 1 U1 0 U2 9 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 EI 1949-3614 J9 ASSIST TECHNOL JI Assist. Technol. PY 2013 VL 25 IS 4 BP 181 EP 193 DI 10.1080/10400435.2012.747572 PG 13 WC Rehabilitation SC Rehabilitation GA 257OM UT WOS:000327394300001 PM 24620701 ER PT J AU Pearlman, J Cooper, R Duvall, J Livingston, R AF Pearlman, Jonathan Cooper, Rory Duvall, Jonathan Livingston, Ryan TI Pedestrian Pathway Characteristics and Their Implications on Wheelchair Users SO ASSISTIVE TECHNOLOGY LA English DT Article DE accessible; pathway; roughness; whole-body vibrations ID WHOLE-BODY VIBRATION; LOW-BACK-PAIN; SURFACES AB Individuals who use wheelchairs (WCs) frequently navigate over pathways with obstacles (e.g., bumps or curb descents) or terrain that is extremely rough. Surface characteristics such as roughness can have an effect on comfort and variables associated with bodily injury. Understanding these relationships can be helpful to ensure safe and comfortable access to all public and private pathways. This article reviews existing research related to the topics of surface roughness effects on WC user's bodies, surface roughness measurement techniques, and design guidelines and exposure limits that attempt to ensure pathways are safe and passable. These findings are discussed along with opportunities to improve them. Using a broad literature search, it was found that several measurement and analysis techniques exist to characterize surface roughness related to automobile roadways, but they have not been systematically applied to WC use over pedestrian pathways. The roughness measurement approach that appears most relevant and adaptable for sidewalks are rolling profilers. Commercially available devices could be recalibrated or adapted to measure pedestrian pathways. IRI and ride-quality analysis techniques appear most relevant and could also be adapted. Any analysis technique that uses profiles of surfaces should focus on frequencies and wavelengths that are most applicable to WC riders. C1 [Pearlman, Jonathan; Cooper, Rory; Duvall, Jonathan; Livingston, Ryan] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, VA Rehabil Res & Dev Ctr Excellence Wheelchairs &, Pittsburgh, PA 15206 USA. [Pearlman, Jonathan; Cooper, Rory; Duvall, Jonathan; Livingston, Ryan] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Pearlman, Jonathan; Cooper, Rory; Duvall, Jonathan; Livingston, Ryan] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Pearlman, Jonathan; Cooper, Rory; Duvall, Jonathan; Livingston, Ryan] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. RP Pearlman, J (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, 6425 Penn Ave,Suite 400, Pittsburgh, PA 15206 USA. EM jlp46@pitt.edu OI Pearlman, Jon/0000-0003-0830-9136 NR 26 TC 1 Z9 1 U1 0 U2 1 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 EI 1949-3614 J9 ASSIST TECHNOL JI Assist. Technol. PY 2013 VL 25 IS 4 BP 230 EP 239 DI 10.1080/10400435.2013.778915 PG 10 WC Rehabilitation SC Rehabilitation GA 257OM UT WOS:000327394300006 PM 24620706 ER PT J AU Seyyedi, M Burgess, BJ Eddington, DK Gantz, BJ Nadol, JB AF Seyyedi, M. Burgess, B. J. Eddington, D. K. Gantz, B. J. Nadol, J. B., Jr. TI Histopathology of the Clarion Cochlear Implant Electrode Positioner in a Human Subject SO AUDIOLOGY AND NEURO-OTOLOGY LA English DT Article DE Histopathology; Clarion (R) cochlear implant; Positioner; Human temporal bone histopathology ID HUMAN TEMPORAL BONES; MENINGITIS; INTRACOCHLEAR; TRAUMA; ARRAY; RISK AB A Silastic electrode positioner was introduced by the Advanced Bionics Corporation in 1999 and it was designed to achieve a perimodiolar position of the stimulating electrode. The positioner was voluntarily recalled in the United States in July 2002 due to an apparent higher risk of bacterial meningitis in patients in whom the electrode positioner had been placed. A detailed histopathologic study of the positioner in the human has not previously been published. The histopathologic findings in a 74-year-old woman who underwent bilateral cochlear implantation using the positioner are presented. Findings include a large track caused by the combined electrode and its positioner with considerable disruption of the basilar membrane and osseous spiral lamina. Although there was a fibrous sheath around the electrode and positioner at the cochleostomy in both ears, this fibrous sheath did not extend deeply into the cochlea except at the apical end of the electrode beyond the positioner. This resulted in a large fluid space around and between the positioner and electrode within the cochlea and presumably in fluid continuity with the cerebrospinal fluid space. Possible clinical implications are discussed. Copyright (C) 2013 S. Karger AG, Basel C1 [Seyyedi, M.; Burgess, B. J.; Eddington, D. K.; Nadol, J. B., Jr.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Seyyedi, M.; Burgess, B. J.; Eddington, D. K.; Nadol, J. B., Jr.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Gantz, B. J.] Univ Iowa Hosp & Clin, Dept Otolaryngol Head & Neck Surg, Iowa City, IA 52242 USA. RP Nadol, JB (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM joseph_nadol@meei.harvard.edu FU NIDCD NIH HHS [P50 DC000242, R01 DC000152] NR 15 TC 2 Z9 3 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-3030 EI 1421-9700 J9 AUDIOL NEURO-OTOL JI Audiol. Neuro-Otol. PY 2013 VL 18 IS 4 BP 223 EP 227 DI 10.1159/000351300 PG 5 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 258MN UT WOS:000327463500004 PM 23774789 ER PT J AU Heyman, SN Rosenberger, C Rosen, S Khamaisi, M AF Heyman, Samuel N. Rosenberger, Christian Rosen, Seymour Khamaisi, Mogher TI Why Is Diabetes Mellitus a Risk Factor for Contrast-Induced Nephropathy? SO BIOMED RESEARCH INTERNATIONAL LA English DT Review ID ACUTE-RENAL-FAILURE; ACUTE KIDNEY INJURY; RADIOCONTRAST-INDUCED NEPHROPATHY; ENDOTHELIN-CONVERTING ENZYME-1; ATRIAL-NATRIURETIC-PEPTIDE; GLOMERULAR-FILTRATION-RATE; MEDULLARY HYPOXIC INJURY; NITRIC-OXIDE DEFICIENCY; PROTEIN-KINASE-C; RECEPTOR ANTAGONIST AB Contrast-induced nephropathy (CIN) remains a leading cause of iatrogenic acute kidney injury, as the usage of contrast media for imaging and intravascular intervention keeps expanding. Diabetes is an important predisposing factor for CIN, particularly in patients with renal functional impairment. Renal hypoxia, combined with the generation of reactive oxygen species, plays a central role in the pathogenesis of CIN, and the diabetic kidney is particularly susceptible to intensified hypoxic and oxidative stress following the administration of contrast media. The pathophysiology of this vulnerability is complex and involves various mechanisms, including a priori enhanced tubular transport activity, oxygen consumption, and the generation of reactive oxygen species. The regulation of vascular tone and peritubular blood flow may also be altered, particularly due to defective nitrovasodilation, enhanced endothelin production, and a particular hyperresponsiveness to adenosine-related vasoconstriction. In addition, micro-and macrovascular diseases and chronic tubulointerstitial changes further compromise regional oxygen delivery, and renal antioxidant capacity might be hampered. A better understanding of these mechanisms and their control in the diabetic patient may initiate novel strategies in the prevention of contrast nephropathy in these susceptible patients. C1 [Heyman, Samuel N.] Hadassah Hebrew Univ Hosp, Dept Med, Mt Scopus, Israel. [Heyman, Samuel N.] Hebrew Univ Jerusalem, Sch Med, IL-91240 Jerusalem, Israel. [Rosenberger, Christian] Charite Campus Mitte, Dept Nephrol, D-10115 Berlin, Germany. [Rosen, Seymour] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Rosen, Seymour] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Khamaisi, Mogher] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Heyman, SN (reprint author), Hadassah Hebrew Univ Hosp, Dept Med, Mt Scopus, Israel. EM heyman@cc.huji.ac.il NR 69 TC 11 Z9 12 U1 0 U2 3 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2013 AR 123589 DI 10.1155/2013/123589 PG 8 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 260VU UT WOS:000327623400001 ER PT J AU Wortzel, HS Shura, RD Brenner, LA AF Wortzel, Hal S. Shura, Robert D. Brenner, Lisa A. TI Chronic Traumatic Encephalopathy and Suicide: A Systematic Review SO BIOMED RESEARCH INTERNATIONAL LA English DT Review ID FOOTBALL-LEAGUE PLAYER; BRAIN-INJURY AB Traumatic brain injury (TBI) is a global health concern, and the recent literature reports that a single mild TBI can result in chronic traumatic encephalopathy (CTE). It has been suggested that CTE may lead to death by suicide, raising important prevention, treatment, and policy implications. Thus, we conducted a systematic review of the medical literature to answer the key question: What is the existing evidence in support of a relationship between CTE and suicide? Systematic searches of CTE and suicide yielded 85 unique abstracts. Seven articles were identified for full text review. Only two case series met inclusion criteria and included autopsies from 17 unique cases, 5 of whom died by suicide. Neither studies used blinding, control cases, or systematic data collection regarding TBI exposure and/or medical/neuropsychiatric history. The identified CTE literature revealed divergent opinions regarding neuropathological elements of CTE and heterogeneity regarding clinical manifestations. Overall quality of evidence regarding a relationship between CTE and suicide was rated as very low using Grading of Recommendations Assessment, Development and Evaluation Working Group (GRADE) criteria. Further studies of higher quality and methodological rigor are needed to determine the existence and nature of any relationship between CTE and suicide. C1 [Wortzel, Hal S.; Shura, Robert D.; Brenner, Lisa A.] Denver Vet Affairs Med Ctr, Res Educ & Clin Ctr, VISN, Dept Psychiat, Denver, CO 80220 USA. [Wortzel, Hal S.; Shura, Robert D.; Brenner, Lisa A.] Denver Vet Affairs Med Ctr, Res Educ & Clin Ctr, VISN, Dept Neurol, Denver, CO 80220 USA. [Wortzel, Hal S.; Shura, Robert D.; Brenner, Lisa A.] Denver Vet Affairs Med Ctr, Res Educ & Clin Ctr, VISN, Dept Phys Med & Rehabil, Denver, CO 80220 USA. [Wortzel, Hal S.; Brenner, Lisa A.] Univ Colorado, Sch Med, Dept Psychiat, Denver, CO 80045 USA. [Wortzel, Hal S.; Brenner, Lisa A.] Univ Colorado, Sch Med, Dept Neurol, Denver, CO 80045 USA. [Shura, Robert D.] Marshall Univ, Dept Psychol, Huntington, WV 25755 USA. RP Wortzel, HS (reprint author), Denver Vet Affairs Med Ctr, Res Educ & Clin Ctr, VISN, Dept Psychiat, 19 Mental Illness, Denver, CO 80220 USA. EM hal.wortzel@ucdenver.edu OI Shura, Robert/0000-0002-9505-0080 FU Department of Veterans Affairs FX This paper is based on work supported, in part, by the Department of Veterans Affairs but does not necessarily represent the views of the Department of Veterans Affairs or the United States Government. NR 24 TC 11 Z9 11 U1 3 U2 5 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2013 AR 424280 DI 10.1155/2013/424280 PG 6 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 261ED UT WOS:000327646100001 ER PT J AU Eberlin, KR Vyas, RM Abi-Haidar, Y Sethna, N Hamdan, US AF Eberlin, Kyle R. Vyas, Raj M. Abi-Haidar, Youmna Sethna, Navil Hamdan, Usama S. TI Adult Cleft Lip Repair Under Local Anesthesia: An Effective Technique in Resource-Poor Settings SO CLEFT PALATE-CRANIOFACIAL JOURNAL LA English DT Article DE cleft lip; local anesthesia; medical missions ID EXTERNAL NASAL NERVE; ZIMBABWE; CHILDREN; PALATE; BLOCK AB Objective: In developing countries there are many adults with unrepaired cleft lip deformities. These countries often lack the equipment and personnel to provide general anesthesia for all patients; therefore, a technique for repair under local anesthesia would be useful. Method: A retrospective review was performed of 22 adolescent/adult patients on whom primary cleft lip repair was performed under local anesthesia in Bamako, Mali, in 2008 and 2009. Inclusion criteria for this technique were age greater than 12 with unilateral or bilateral deformity and ability to understand and tolerate the procedure under local anesthesia alone. Exclusion criteria included cardiopulmonary disease or inability to tolerate the procedure while awake. Demographic information and outcome data were collected including total time in the operating room, surgical time, and day of discharge. Results: Twenty-two primary cleft lip repairs were completed in 12 male and 10 female patients. Mean age was 22.3 years and mean weight was 50 kg. Overall, mean total operating room time was 145 minutes. Mean operating room time was significantly (p < .01) longer in 2008 (159 minutes) than in 2009 (114 minutes). Although mean surgical time was 110 minutes, there was a similar significant (p = .03) decrease from 2008 (119 minutes) to 2009 (91 minutes). All patients tolerated the procedure without requiring intubation or intravenous sedation, and all were discharged the same day. Conclusion: Cleft lip repair in adults under local anesthesia is safe and effective. Improvements in technique and efficiency have made this valuable in developing countries. C1 [Eberlin, Kyle R.; Vyas, Raj M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Plast Surg Training Program, Boston, MA USA. [Abi-Haidar, Youmna] Tufts Univ, Surg Training Program, Boston, MA 02111 USA. [Sethna, Navil] Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA. [Hamdan, Usama S.] Global Smile Fdn, Boston, MA USA. [Hamdan, Usama S.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Hamdan, Usama S.] Harvard Univ, Sch Med, Boston, MA USA. [Hamdan, Usama S.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Eberlin, KR (reprint author), Massachusetts Gen Hosp, Harvard Plast Surg Training Program, Div Plast Surg, 55 Fruit St,WAC 43, Boston, MA 02114 USA. EM keberlin@partners.org NR 16 TC 1 Z9 1 U1 0 U2 2 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1545-1569 EI 1055-6656 J9 CLEFT PALATE-CRAN J JI Cleft Palate-Craniofac. J. PD JAN PY 2013 VL 50 IS 1 BP 59 EP 63 DI 10.1597/11-256 PG 5 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA 259NE UT WOS:000327532800008 PM 22303999 ER PT J AU Fung, CH Martin, JL Dzierzewski, JM Jouldjian, S Josephson, K Park, M Alessi, C AF Fung, Constance H. Martin, Jennifer L. Dzierzewski, Joseph M. Jouldjian, Stella Josephson, Karen Park, Michelle Alessi, Cathy TI Prevalence and Symptoms of Occult Sleep Disordered Breathing among Older Veterans with Insomnia SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE Sleep disordered breathing; prevalence; risk factors; older adults; comorbid insomnia ID COMORBID INSOMNIA; APNEA SYNDROME; ASSOCIATION; POPULATION; COMMUNITY; ADULTS; PATIENT; HEALTH; DEVICE; SAMPLE AB Study Objectives: To determine the prevalence of occult sleep disordered breathing (SDB) and describe the relationship between classic SDB symptoms (e. g., loud snoring) and occult SDB in older veterans with insomnia. Methods: We analyzed baseline survey and in-home sleep study data for 435 veterans (mean age = 72.0 years [SD 8.0]) who had no known history of SDB, met International Classification of Sleep Disorders 2nd Edition criteria for insomnia, and were enrolled in a behavioral intervention trial for insomnia. Variables of interest included apnea-hypopnea index (AHI) >= 15, age, race/ethnicity, marital status, body mass index (BMI), insomnia subtype (i.e., onset, maintenance, or terminal), self-reported excessive daytime sleepiness, snoring, and witnessed breathing pause items from the Berlin Questionnaire. We computed the frequency of AHI = 15 and assessed whether each classic SDB symptom was associated with an AHI = 15 in 4 separate multivariate logistic regression models. Results: Prevalence of AHI >= 15 was 46.7%. Excessive daytime sleepiness (adjusted odds ratio 1.63, 95% CI 1.02, 2.60, p = 0.04), but not snoring loudness, snoring frequency, or witnessed breathing pauses was associated with occult SDB (AHI >= 15). Insomnia subtypes were not significantly associated with occult SDB (p > 0.38). Conclusions: In our sample of older veterans with insomnia, nearly half had occult SDB, which was characterized by reported excessive daytime sleepiness, but not loud or frequent snoring or witnessed breathing pauses. Insomnia subtype was unrelated to the presence of occult SDB. C1 [Fung, Constance H.; Martin, Jennifer L.; Dzierzewski, Joseph M.; Jouldjian, Stella; Josephson, Karen; Alessi, Cathy] Vet Adm Greater Los Angeles Healthcare Syst, GRECC, Los Angeles, CA USA. [Fung, Constance H.; Martin, Jennifer L.; Dzierzewski, Joseph M.; Alessi, Cathy] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Park, Michelle] Western Univ Hlth Sci, Pomana, CA USA. RP Fung, CH (reprint author), VA Greater Los Angeles Healthcare Syst, 16111 Plummer St, North Hills, CA 91343 USA. EM Connie.Fung@va.gov FU Department of Veterans Affairs Advanced Geriatrics Fellowship Program; Veterans Administration Health Services Research and Development [IIR 08-295]; American Sleep Medicine Foundation Physician Scientist Training Award; Veterans Administration Greater Los Angeles Geriatric Research, Education and Clinical Center, American Federation for Aging Research; Medical Student Training in Aging Research Program, National Institute on Aging [T35AG026736]; John A. Hartford Foundation; MetLife Foundation; Lillian R. Gleitsman Foundation FX Funded by the Department of Veterans Affairs Advanced Geriatrics Fellowship Program (Fung, Dzierzewski), Veterans Administration Health Services Research and Development (Alessi IIR 08-295), the American Sleep Medicine Foundation Physician Scientist Training Award (Fung), Veterans Administration Greater Los Angeles Geriatric Research, Education and Clinical Center, American Federation for Aging Research (Fung), Medical Student Training in Aging Research Program, National Institute on Aging (Park T35AG026736), the John A. Hartford Foundation (Fung, Park), the MetLife Foundation (Park), and the Lillian R. Gleitsman Foundation (Park). The authors have indicated no financial conflicts of interest. All work was completed at VA Greater Los Angeles Healthcare System. This study did not involve any off-label or investigational use. NR 38 TC 6 Z9 7 U1 1 U2 2 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 EI 1550-9397 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2013 VL 9 IS 11 BP 1173 EP 1178 DI 10.5664/jcsm.3162 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 256PZ UT WOS:000327327300009 PM 24235899 ER PT J AU Montesi, SB Bakker, JP Macdonald, M Hueser, L Pittman, S White, DP Malhotra, A AF Montesi, Sydney B. Bakker, Jessie P. Macdonald, Mary Hueser, Lauren Pittman, Stephen White, David P. Malhotra, Atul TI Air Leak during CPAP Titration as a Risk Factor for Central Apnea SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE Sleep apnea; air leak; central apnea ID OBSTRUCTIVE SLEEP-APNEA; CONGESTIVE-HEART-FAILURE; PRESSURE; CONSEQUENCES; RESPIRATION AB Objectives: Emergence of central sleep apnea has been described in the setting of continuous positive airway pressure (CPAP) initiation. The underlying mechanism is unclear; however, we postulate that air leak washing out anatomical dead space is a contributing factor. Design: Data were obtained from 310 patients with obstructive sleep apnea (OSA) who underwent either split-night or full-night CPAP titration during January to July of 2009. The majority (n = 245) underwent titration with a nasal mask. Average total leak and maximum total leak were measured at therapeutic CPAP level. Unintentional leak was calculated by subtracting manufacturer-defined intentional leak from maximum leak. Results: Subjects were divided into two groups: central apnea index (CAI) during titration < 5/hour and >= 5/hour. The groups were similar in terms of gender, age, BMI, and AHI. The CAI < 5 group had a median average leak of 45.5 L/min (IQR 20.8 L/min) versus 51.0 L/min (IQR 21.0 L/min) with CAI >= 5 (p = 0.056). Maximum leak was 59.5 L/min (IQR 27.0 L/min) with CAI < 5 and 75.0 L/min (IQR 27.8 L/min) with CAI >= 5 (p = 0.003). In the subset of subjects titrated using a nasal mask, median average leak was 42.0 L/min (IQR 17.0) in the CAI < 5 group and 50.0 L/min (IQR 16.8) in the CAI >= 5 group (p = 0.001). In the CAI < 5 group, median maximum leak was 57.0 L/min (IQR 23.0) versus 74.5 L/min (IQR 24.3) in the CAI >= 5 group (p < 0.001). Conclusions: Leak during CPAP titration is associated with the development of acute central apnea; these data may have mechanistic and therapeutic implications for complex apnea. C1 [Montesi, Sydney B.; Bakker, Jessie P.; White, David P.; Malhotra, Atul] Brigham & Womens Hosp, Sleep Disorders Res Program, Boston, MA 02115 USA. [Montesi, Sydney B.; Bakker, Jessie P.; White, David P.; Malhotra, Atul] Harvard Univ, Sch Med, Boston, MA USA. [Montesi, Sydney B.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Macdonald, Mary; Hueser, Lauren; Pittman, Stephen; White, David P.] Philips Respiron, Boston, MA USA. [Malhotra, Atul] Univ Calif San Diego, Div Pulm & Crit Care Med, San Diego, CA USA. RP Montesi, SB (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, 55 Fruit St, Boston, MA 02114 USA. EM sbmontesi@partners.org NR 25 TC 10 Z9 10 U1 0 U2 2 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 1550-9389 EI 1550-9397 J9 J CLIN SLEEP MED JI J. Clin. Sleep Med. PY 2013 VL 9 IS 11 BP 1187 EP 1191 DI 10.5664/jcsm.3166 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 256PZ UT WOS:000327327300011 PM 24235901 ER PT S AU Dayal, P Kuksenok, O Bhattacharya, A Buxton, GA Usta, OB Balazs, AC AF Dayal, Pratyush Kuksenok, Olga Bhattacharya, Amitabh Buxton, Gavin A. Usta, O. Berk Balazs, Anna C. BE DenToonder, JMJ Onck, PR TI Modeling the Interaction of Active Cilia with Species in Solution: From Chemical Reagents to Microscopic Particles SO ARTIFICIAL CILIA SE RSC Nanoscience and Nanotechnology LA English DT Article; Book Chapter ID SELF-OSCILLATING GEL; LOW-REYNOLDS-NUMBER; ARTIFICIAL CILIA; BIOMIMETIC CILIA; PERISTALTIC MOTION; POLYMER GELS; PROPULSION; TRANSPORT; DYNAMICS; TARGET C1 [Dayal, Pratyush] Indian Inst Technol, Dept Chem Engn, Gandhinagar, India. [Kuksenok, Olga; Bhattacharya, Amitabh; Balazs, Anna C.] Univ Pittsburgh, Dept Chem & Petr Engn, Pittsburgh, PA 15261 USA. [Buxton, Gavin A.] Robert Morris Univ, Moon Township, PA 15108 USA. [Usta, O. Berk] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. [Usta, O. Berk] Shriners Hosp Children, Boston, MA 02114 USA. RP Dayal, P (reprint author), Indian Inst Technol, Dept Chem Engn, Gandhinagar, India. EM balazs@pitt.edu NR 64 TC 0 Z9 0 U1 2 U2 3 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND SN 1757-7136 BN 978-1-84973-709-8; 978-1-84973-597-1 J9 RSC NANOSCI NANOTECH PY 2013 IS 30 BP 63 EP 88 D2 10.1039/9781849737098 PG 26 WC Nanoscience & Nanotechnology SC Science & Technology - Other Topics GA BHX65 UT WOS:000326958200005 ER PT J AU Watkins, ML Wilcox, TK Tabberer, M Brooks, JM Donohue, JF Anzueto, A Chen, WH Crim, C AF Watkins, Michael L. Wilcox, Teresa K. Tabberer, Maggie Brooks, Jean M. Donohue, James F. Anzueto, Antonio Chen, Wen-Hung Crim, Courtney TI Shortness of Breath with Daily Activities questionnaire: validation and responder thresholds in patients with chronic obstructive pulmonary disease SO BMJ OPEN LA English DT Article DE THORACIC MEDICINE; RESPIRATORY MEDICINE (see Thoracic Medicine) ID QUALITY-OF-LIFE; COPD AB Objectives To test the reliability, validity and responsiveness of the 13-item Shortness of Breath with Daily Activities (SOBDA) questionnaire, and determine the threshold for response and minimal important difference (MID). Design 6week, randomised, double-blind, placebo-controlled study. Setting 40 centres in the USA between 29 October 2009 and 1 July 2010. Primary and secondary outcome measures 547 patients with chronic obstructive pulmonary disease (COPD) were enrolled and 418 entered the 2-week run-in period. Data from the run-in period were collected to test internal consistency, test-retest reliability, convergent validity and known-groups validity of the SOBDA. Three hundred and sixty six patients were randomised 2:2:1 to fluticasone propionate/salmeterol 250/50 mu g, salmeterol 50 mu g or placebo, twice daily. Results from the SOBDA questionnaire, Patient Global Assessment of Change Question, modified Medical Research Council Dyspnoea Scale (mMRC), Clinician Global Impression of Dysponea Severity (CGI-S), Clinician Global Impression of Change Question and Chronic Respiratory Disease Questionnaire self-administered standardised version (CRQ-SAS) were evaluated; spirometry and safety parameters were measured. Study endpoints were selected to investigate the cross-sectional and longitudinal validity of the SOBDA questionnaire in relation to the clinical criteria. Results Internal consistency of the SOBDA questionnaire (Cronbach ) was 0.89. Test-retest reliability (intraclass correlation) was 0.94. The SOBDA weekly scores correlated with the patient-reported and clinician-reported mMRC, CGI-S and CRQ-SAS dyspnoea domain scores (0.29, 0.24, 0.24 and -0.68, respectively). The SOBDA weekly scores differentiated between the responders and the non-responders as rated by the patients and the clinicians. Anchor-based and supportive distribution-based analyses produced a range of the potential values for the threshold for the responders and MID. Conclusions The 13-item SOBDA questionnaire is reliable, valid and responsive to change in patients with COPD. On using anchor-based methods, the proposed responder threshold shows a -0.1 to -0.2 score change. A specific threshold value will be identified as more data are generated from future clinical trials. Trial registration NCT00984659; GlaxoSmithKline study number: ASQ112989. C1 [Watkins, Michael L.; Crim, Courtney] GlaxoSmithKline, Resp Med Dev Ctr, Res Triangle Pk, NC 27709 USA. [Wilcox, Teresa K.; Chen, Wen-Hung] Evidera, United BioSource Corp, Bethesda, MD USA. [Tabberer, Maggie; Brooks, Jean M.] GlaxoSmithKline, Resp Med Dev Ctr, Uxbridge, Middx, England. [Donohue, James F.] Univ N Carolina, Div Pulm & Crit Care Med, Chapel Hill, NC USA. [Anzueto, Antonio] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Watkins, ML (reprint author), GlaxoSmithKline, Resp Med Dev Ctr, Res Triangle Pk, NC 27709 USA. EM michael.l.watkins@gsk.com FU GlaxoSmithKline FX The SOBDA development programme, including this ASQ112989 study, was funded by GlaxoSmithKline. GlaxoSmithKline and Evidera (formerly United BioSource Corporation) developed the instrument. GlaxoSmithKline had a role in the study design, data collection and analyses, decision to publish and in the preparation of all study reporting including this manuscript. NR 16 TC 9 Z9 9 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 2013 VL 3 IS 10 AR e003048 DI 10.1136/bmjopen-2013-003048 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 250UY UT WOS:000326882800005 PM 24154513 ER PT J AU Cantley, J Walters, SN Jung, MH Weinberg, A Cowley, MJ Whitworth, PT Kaplan, W Hawthorne, WJ O'Connell, PJ Weir, G Grey, ST AF Cantley, James Walters, Stacey N. Jung, Min-Ho Weinberg, Anita Cowley, Mark J. Whitworth, P. Tess Kaplan, Warren Hawthorne, Wayne J. O'Connell, Philip J. Weir, Gordon Grey, Shane T. TI A Preexistent Hypoxic Gene Signature Predicts Impaired Islet Graft Function and Glucose Homeostasis SO CELL TRANSPLANTATION LA English DT Article DE Islet transplantation; Hypoxia; Glycolysis; Hypoxia-inducible factor-1 alpha (HIP-1 alpha) ID NF-KAPPA-B; BETA-CELL FUNCTION; PANCREATIC-ISLETS; INSULIN-SECRETION; TRANSPLANTATION; EXPRESSION; RAT; OXYGEN; VASCULARIZATION; METABOLISM AB We examined whether hypoxic exposure prior to the event of transplantation would have a positive or negative effect upon later islet graft function. Mouse islets exposed to hypoxic culture were transplanted into syngeneic recipients. Islet graft function, beta-cell physiology, as well as molecular changes were examined. Expression of hypoxia-response genes in human islets pre- and posttransplant was examined by microarray. Hypada-preexposed murine islet grafts provided poor glycemic control in their syngeneic recipients, marked by persistent hyperglycemia and pronounced glucose intolerance with failed first- and second-phase glucose-stimulated insulin secretion in vivo. Mechanistically, hypoxic preexposure stabilized HIF-1 alpha with a concomitant increase in hypoxic-response genes including LDHA, and a molecular gene set, which would favor glycolysis and lactate production and impair glucose sensing. Indeed, static incubation studies showed that hypoxia-exposed islets exhibited dysregulated glucose responsiveness with elevated basal insulin secretion. Isolated human islets, prior to transplantation, express a characteristic hypoxia-response gene expression signature, including high levels of LDHA, which is maintained posttransplant. Hypoxic preexposure of an islet graft drives a HIF-dependent switch to glycolysis with subsequent poor glycemic control and loss of glucose-stimulated insulin secretion (GSIS). Early intervention to reverse or prevent these hypoxia-induced metabolic gene changes may improve clinical islet transplantation. C1 [Cantley, James; Whitworth, P. Tess] Garvan Inst, Diabet & Obes Res Program, Darlinghurst, NSW, Australia. [Cantley, James; Walters, Stacey N.; Weinberg, Anita; Cowley, Mark J.; Whitworth, P. Tess; Kaplan, Warren; Grey, Shane T.] Univ New S Wales, St Vincents Clin Sch, Fac Med, Darlinghurst, NSW, Australia. [Walters, Stacey N.; Weinberg, Anita; Grey, Shane T.] Garvan Inst, Program Immunol, Darlinghurst, NSW, Australia. [Jung, Min-Ho; Weir, Gordon] Joslin Diabet Ctr, Islet Cell & Regenerat Biol, Boston, MA 02215 USA. [Cowley, Mark J.] Garvan Inst, Canc Program, Darlinghurst, NSW, Australia. [Kaplan, Warren] Garvan Inst, Peter Wills Bioinformat Ctr, Darlinghurst, NSW, Australia. [Hawthorne, Wayne J.; O'Connell, Philip J.] Westmead Hosp, Ctr Transplant & Renal Res, Westmead, NSW 2145, Australia. RP Grey, ST (reprint author), St Vincents Hosp, Garvan Inst Med Res, Gene Therapy & Autoimmun Grp, Program Immunol, 384 Victoria St, Darlinghurst, NSW 2010, Australia. EM s.grey@garvan.org.au RI Grey, Shane/B-3020-2008; OI Grey, Shane/0000-0003-2160-1625; Cowley, Mark/0000-0002-9519-5714 FU National Health and Medical Research (NHMRC) [427695, 427828]; American Diabetes Association; Juvenile Diabetes Research Foundation; National Institutes of Health [R01 DK66056, P30 DK36836]; Diabetes Australia Research Trust; Ross Trust Fellowship FX The authors thank Associate Professor Sof Androkopoulos, Department of Medicine, University of Melbourne, Australia; as well as Dr Ross Laybutt, Diabetes and Obesity Research Program, Garvan Institute, Australia, for the itzsigh011 critique and helpful discussion. The authors acknowledge the technical expertise of Helen Speirs from the Ramaciotti Centre University of New South Wales regarding microarrays; as well as Anita Patel and Lindy Williams from the clinical islet isolation team at Westmead Hospital, Westmead, Australia. Work by S.N.W., A.W., M.J.C., WK, and S.T.G. was supported by the National Health and Medical Research (NHMRC) grants 427695 and 427828 to S.T.G. Work by G.C.W. and M.H.J. was supported by grants from the American Diabetes Association, the Juvenile Diabetes Research Foundation, the National Institutes of Health (R01 DK66056 and P30 DK36836 - the Advanced Microscopy, Bioinformatics, and Genomics Cores of Joslin Diabetes and Endocrinology Research Center). J. C. holds the Wertel Fellowship, awarded by the Diabetes Australia Research Trust. S.1V.W. is the recipient of a Ross Trust Fellowship. S.T.G. is an Australian Research Council Future Fellow and Honorary NHMRC Senior Research Fellow. Dr Shane T Grey is the guarantor of this work, had full access to all the data, and takes full responsibility for the integrity of data and the accuracy of data analysis. J.C., S.N.W., M.H., A.W., M.J.C., WK., and S.T.G. researched the data. M.H.J. and G. W. conducted microarray laser-dissected human /I-cell studies. W.J.H. and P.O.C. from the Australian Islet Transplant Consortium provided access to isolated human islets. J.C., S.N.W., G.W., and S.T.G. wrote and edited the manuscript. The authors declare no conflicts of interest. NR 46 TC 6 Z9 6 U1 0 U2 2 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0963-6897 EI 1555-3892 J9 CELL TRANSPLANT JI Cell Transplant. PY 2013 VL 22 IS 11 BP 2147 EP 2159 DI 10.3727/096368912X658728 PG 13 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 253SI UT WOS:000327109200015 PM 23127310 ER PT J AU Turan, S Bastepe, M AF Turan, Serap Bastepe, Murat TI The GNAS Complex Locus and Human Diseases Associated with Loss-of-Function Mutations or Epimutations within This Imprinted Gene SO HORMONE RESEARCH IN PAEDIATRICS LA English DT Review DE GNAS; Pseudohypoparathyroidism; alpha-Subunit of the stimulatory G protein ID PSEUDOHYPOPARATHYROIDISM-TYPE-IB; XL-ALPHA-S; ALBRIGHT HEREDITARY OSTEODYSTROPHY; PROGRESSIVE OSSEOUS HETEROPLASIA; G-PROTEIN; GS-ALPHA; AUTOSOMAL-DOMINANT; HORMONE RESISTANCE; CONTROL REGION; PARATHYROID-HORMONE AB GNAS is a complex imprinted locus leading to several different gene products that show exclusive monoallelic expression. GNAS also encodes the a-subunit of the stimulatory G protein (Gs alpha), a ubiquitously expressed signaling protein that is essential for the actions of many hormones and other endogenous molecules. Gsa is expressed biallelically in most tissues but its expression is silenced from the paternal allele in a small number of tissues. The tissue-specific paternal silencing of Gsa results in different parent-of-origin-specific phenotypes in patients who carry inactivating GNAS mutations. In this paper, we review the GNAS complex locus and discuss how disruption of Gsa expression and the expression of other GNAS products shape the phenotypes of human disorders caused by mutations in this gene. (C) 2013 S. Karger AG, Basel C1 [Turan, Serap] Marmara Univ Sch Med Hosp, Istanbul, Turkey. [Bastepe, Murat] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. [Bastepe, Murat] Harvard Univ, Sch Med, Boston, MA USA. RP Turan, S (reprint author), Marmara Univ Hosp, Fevzi Cakmak Mh Mimar Sinan Cd 41, TR-34899 Istanbul, Turkey. FU National Institute of Diabetes and Digestive and Kidney Diseases; March of Dimes Foundation; Milton Fund; European Society for Paediatric Endocrinology through Lilly USA, LLC. FX The studies conducted in the laboratory of M. B. were funded in part by research grants from the National Institute of Diabetes and Digestive and Kidney Diseases, the March of Dimes Foundation, and the Milton Fund. S. T. was supported by a Sabbatical Leave Programme grant from the European Society for Paediatric Endocrinology through an educational grant from Lilly USA, LLC. NR 110 TC 13 Z9 13 U1 0 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1663-2818 EI 1663-2826 J9 HORM RES PAEDIAT JI Horm. Res. Paediatr. PY 2013 VL 80 IS 4 BP 229 EP 241 DI 10.1159/000355384 PG 13 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 251NB UT WOS:000326934800002 PM 24107509 ER PT J AU Thomas, GA Alvarez-Reeves, M Lu, LG Yu, H Irwin, ML AF Thomas, Gwendolyn A. Alvarez-Reeves, Marty Lu, Lingeng Yu, Herbert Irwin, Melinda L. TI Effect of Exercise on Metabolic Syndrome Variables in Breast Cancer Survivors SO INTERNATIONAL JOURNAL OF ENDOCRINOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; RISK REDUCTION INTERVENTION; POSTMENOPAUSAL WOMEN; PHYSICAL-ACTIVITY; LIFE-STYLE; INSULIN-RESISTANCE; DIABETES-MELLITUS; DEFINED EXERCISE; BODY-FAT; WEIGHT AB Objective. Breast cancer survivors are highly sedentary, overweight, or obese, which puts themat increased risk for comorbid chronic disease. We examined the prevalence of, and changes in, metabolic syndrome following 6 months of an aerobic exercise versus usual care intervention in a sample of sedentary postmenopausal breast cancer survivors. Design andMethods. 65 participants were randomized to an aerobic exercise intervention ( EX) (n = 35) mean BMI 30.8 (+/- 5.9) kg/m (2) or usual care (UC) (n = 30) mean BMI 29.4 (+/- 7.4) kg/m 2. Metabolic syndrome prevalence was determined, as well as change in criteria and overall metabolic syndrome. Results. At baseline, 55.4% of total women met the criteria for metabolic syndrome. There was no statistically significant change in metabolic syndrome when comparing EX and UC. However, adhering to the exercise intervention ( at least 120 mins/week of exercise) resulted in a significant (n =.009) decrease in metabolic syndrome z- score from baseline to 6 months (- 0.76 +/- 0.36) when compared to those who did not adhere ( 0.80 +/- 0.42). Conclusions. Due to a higher prevalence of metabolic syndrome in breast cancer survivors, lifestyle interventions are needed to prevent chronic diseases associated with obesity. Increasing exercise adherence is a necessary target for further research in obese breast cancer survivors. C1 [Thomas, Gwendolyn A.] Yale Univ, New Haven, CT 06520 USA. [Alvarez-Reeves, Marty] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lu, Lingeng; Irwin, Melinda L.] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Yu, Herbert] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA. RP Thomas, GA (reprint author), Yale Univ, New Haven, CT 06520 USA. EM gwendolyn.thomas@gmail.com OI Yu, Herbert/0000-0003-3950-4815 FU American Cancer Society [MRSG- 04- 006-01-CPPB]; Susan G. Komen Breast Cancer Foundation [BCTR0201916]; National Institute of Nursing Research (Research Training: Self and Family Management [T32NR008346]; National Center of Research Resources, National Institutes of Health [M01-RR00125] FX This paper was supported by the American Cancer Society (MRSG- 04- 006-01-CPPB) and the Susan G. Komen Breast Cancer Foundation (BCTR0201916). It was supported in part by the National Institute of Nursing Research (Research Training: Self and Family Management, T32NR008346) and by a General Clinical Research Center Grant from the National Center of Research Resources, National Institutes of Health (Grant no. M01-RR00125) awarded to Yale University School of Medicine. NR 39 TC 4 Z9 4 U1 0 U2 3 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-8337 EI 1687-8345 J9 INT J ENDOCRINOL JI Int. J. Endocrinol. PY 2013 AR 168797 DI 10.1155/2013/168797 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 255WZ UT WOS:000327272100001 ER PT J AU Jasinskas, V Rudalevicius, P Miliauskas, A Milcius, D Jurkunas, UV AF Jasinskas, Vytautas Rudalevicius, Paulius Miliauskas, Arunas Milcius, Darius Jurkunas, Ula V. TI Keratoprosthesis Surgery as an Alternative to Keratoplasty SO MEDICINA-LITHUANIA LA English DT Article DE Boston type 1 keratoprosthesis; artificial cornea; keratoplasty; corneal blindness; glaucoma AB Corneal transplant surgery after chemical or thermal burns has a very low success rate. Vision in these patients can be restored by using an artificial cornea (keratoprosthesis). In this report, we present 5 clinical cases of implanting a fresh corneal graft with Boston type 1 keratoprosthesis in patients with corneas inappropriate for standard corneal transplantation. The mean follow-up was 26.4 months (range, 12 to 36 months; SD, 13.1). The main measures of outcomes were visual acuity and keratoprosthesis stability. At least 1 year after the operation (5 eyes), vision acuity was >0.1 in 100% of the eyes and >0.4 in 50% of the eyes. Retention of the initial keratoprosthesis was 100%. The results of this study seem to be similar to those reported internationally. The anatomical and visual functions of the eyes were stable after keratoprosthesis implantation, though for a longer follow-up period, additional surgical procedures may be required. C1 [Jasinskas, Vytautas; Rudalevicius, Paulius; Miliauskas, Arunas] Lithuanian Univ Hlth Sci, Med Acad, Dept Ophthalmol, LT-50028 Kaunas, Lithuania. [Milcius, Darius] Lithuanian Energy Inst, Kaunas, Lithuania. [Jurkunas, Ula V.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea & Refract Surg Serv, Boston, MA USA. RP Rudalevicius, P (reprint author), Lithuanian Univ Hlth Sci, Med Acad, Dept Ophthalmol, Eiveniu 2, LT-50028 Kaunas, Lithuania. EM pauliusrudalevicius@gmail.com NR 19 TC 2 Z9 2 U1 0 U2 1 PU KAUNAS UNIV MEDICINE & VILNIUS UNIV PI KAUNAS PA KAUNAS UNIV MEDICINE, A MICKEVICIAUS 9, KAUNAS, LT-44307, LITHUANIA SN 1010-660X J9 MED LITH JI Med. Lith. PY 2013 VL 49 IS 6 BP 291 EP 299 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 253SH UT WOS:000327109100007 PM 24248010 ER PT J AU Cadavid, D AF Cadavid, Diego BE Christodoulides, M TI Meningitis in Neuroborreliosis SO MENINGITIS: CELLULAR AND MOLECULAR BASIS SE Advances in Molecular and Cellular Microbiology LA English DT Article; Book Chapter ID LYME-DISEASE SPIROCHETE; RELAPSING-FEVER BORRELIOSIS; OUTER-SURFACE PROTEIN; HUMAN ENDOTHELIAL-CELLS; ANTIGENIC VARIATION; BURGDORFERI LIPOPROTEINS; CLINICAL-MANIFESTATIONS; PERSISTENT INFECTION; CEREBROSPINAL-FLUID; NEUROTROPIC STRAIN C1 [Cadavid, Diego] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Cadavid, Diego] Biogen Idec Inc, Neurol Clin Dev, Cambridge, MA USA. RP Cadavid, D (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. EM cadavid.diego@gmail.com NR 77 TC 0 Z9 0 U1 0 U2 0 PU CABI PUBLISHING-C A B INT PI WALLINGFORD PA CABI PUBLISHING, WALLINGFORD 0X10 8DE, OXON, ENGLAND BN 978-1-78064-162-1 J9 ADV M C M PY 2013 IS 26 BP 213 EP 227 D2 10.1079/9781780641621.0000 PG 15 WC Biochemistry & Molecular Biology; Infectious Diseases; Clinical Neurology SC Biochemistry & Molecular Biology; Infectious Diseases; Neurosciences & Neurology GA BIA48 UT WOS:000327141400016 ER PT S AU Sajjadi, AY Wanyo, CM Fang, QQ Boas, DA Isakoff, SJ Carp, SA AF Sajjadi, Amir Y. Wanyo, Christy M. Fang, Qianqian Boas, David A. Isakoff, Steven J. Carp, Stefan A. BE Tromberg, BJ Yodh, AG SevickMuraca, EM TI Dynamic optical breast imaging for neoadjuvant therapy monitoring SO OPTICAL TOMOGRAPHY AND SPECTROSCOPY OF TISSUE X SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Optical Tomography and Spectroscopy of Tissue X CY FEB 03-06, 2013 CL San Francisco, CA SP SPIE DE Breast cancer; neoadjuvant therapy monitoring; dynamic optical imaging; optical tomography ID CANCER; TOMOGRAPHY; RECONSTRUCTION; CHEMOTHERAPY; MAMMOGRAPHY; COMPRESSION AB Near-infrared optical measurements have been shown to offer a promising non-invasive way for monitoring breast neoadjuvant chemotherapy (NAC) and predicting outcome. In this study, we extend optical measurements to capture additional hemodynamic and metabolic biomarkers revealed by dynamically imaging breast tissue during fractional mammographic compression. We are obtaining pre-treatment, day 7 and optional monthly scans in breast cancer patients undergoing NAC. The difference in hemodynamic response to compression between healthy and tumor-bearing breast decreases over the course of neoadjuvant therapy in responders compared to nearly no change in patients not responding to the chemotherapy. C1 [Sajjadi, Amir Y.; Wanyo, Christy M.; Fang, Qianqian; Boas, David A.; Carp, Stefan A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Sajjadi, AY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM carp@nmr.mgh.harvard.edu NR 13 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9347-7 J9 PROC SPIE PY 2013 VL 8578 AR 85780I DI 10.1117/12.2004884 PG 8 WC Biophysics; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biophysics; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BHU87 UT WOS:000326708600009 ER PT S AU Selb, J Zimmermann, BB Martino, M Ogden, T Boas, DA AF Selb, Juliette Zimmermann, Bernhard B. Martino, Mark Ogden, Tyler Boas, David A. BE Tromberg, BJ Yodh, AG SevickMuraca, EM TI Functional Brain Imaging with a Supercontinuum Time-Domain NIRS System SO OPTICAL TOMOGRAPHY AND SPECTROSCOPY OF TISSUE X SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Optical Tomography and Spectroscopy of Tissue X CY FEB 03-06, 2013 CL San Francisco, CA SP SPIE DE Near-infrared spectroscopy; Time-domain; Time resolved spectroscopy; Supercontinuum laser; Gated detection; Functional Brain Imaging ID OPTICAL-PROPERTIES; RESOLVED REFLECTANCE; SPECTROSCOPY; MEDIA; HEAD AB We have developed the second generation of our time-domain near-infrared spectroscopy (TD-NIRS) system for baseline and functional brain imaging. The instrument uses a pulsed broadband supercontinuum laser emitting a large spectrum between 650 and 1700 nm, and a gated detection based on an intensified CCD camera. The source laser beam is split into two arms, below and above 776 nm. In each arm, a fast motorized filter wheel enables selection of a bandpass filter at the required wavelength. Each filtered laser beam is then launched into one array of source fibers. The multiplexing through the array of fibers is implemented through a very compact home-made design consisting of two galvanometer mirrors followed by an achromatic doublet. Source fibers are then recombined one-by-one from both arms into the source optodes to be positioned on the head. The detection fibers are all imaged in parallel through a relay lens on an intensified CCD camera. By using detection fibers of different lengths, we introduce optical delays that enable simultaneous recording in different delay windows of the temporal point spread functions. We present the instrumentation and show its preliminary functional imaging capabilities. We also introduce a new probe where we use different fiber lengths on the source and the detector sides in order to record simultaneously both wavelengths from one location through different sets of fibers. C1 [Selb, Juliette; Zimmermann, Bernhard B.; Martino, Mark; Ogden, Tyler; Boas, David A.] Massachusetts Gen Hosp, Opt Div, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Selb, J (reprint author), Massachusetts Gen Hosp, Opt Div, Martinos Ctr Biomed Imaging, Bldg 149,13th St, Charlestown, MA 02129 USA. EM juliette@nmr.mgh.harvard.edu NR 14 TC 1 Z9 1 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9347-7 J9 PROC SPIE PY 2013 VL 8578 AR 857807 DI 10.1117/12.2005348 PG 9 WC Biophysics; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biophysics; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BHU87 UT WOS:000326708600005 ER PT S AU Selb, J Ogden, TM Dubb, J Fang, QQ Boas, DA AF Selb, Juliette Ogden, Tyler M. Dubb, Jay Fang, Qianqian Boas, David A. BE Tromberg, BJ Yodh, AG SevickMuraca, EM TI Systematic evaluation of a time-domain Monte Carlo fitting routine to estimate the adult brain optical properties SO OPTICAL TOMOGRAPHY AND SPECTROSCOPY OF TISSUE X SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Optical Tomography and Spectroscopy of Tissue X CY FEB 03-06, 2013 CL San Francisco, CA SP SPIE DE Time Domain; Near-infrared spectroscopy; Monte Carlo; Baseline optical properties; Brain optical properties; Non-linear fit; Two-layer model ID RESOLVED REFLECTANCE MEASUREMENTS; STRONGLY SCATTERING MEDIA; NONINVASIVE DETERMINATION; PHOTON MIGRATION; LAYERED MEDIA; TURBID MEDIA; SPECTROSCOPY; TISSUE; PHANTOM AB Time-domain near-infrared spectroscopy (TD-NIRS) offers the ability to measure the absolute baseline optical properties of a tissue. Specifically, for brain imaging, the robust assessment of cerebral blood volume and oxygenation based on measurement of cerebral hemoglobin concentrations is essential for reliable cross-sectional and longitudinal studies. In adult heads, these baseline measurements are complicated by the presence of thick extra-cerebral tissue (scalp, skull, CSF). A simple semi-infinite homogeneous model of the head has proven to have limited use because of the large errors it introduces in the recovered brain absorption. Analytical solutions for layered media have shown improved performance on Monte-Carlo simulated data and layered phantom experiments, but their validity on real adult head data has never been demonstrated. With the advance of fast Monte Carlo approaches based on GPU computation, numerical methods to solve the radiative transfer equation become viable alternatives to analytical solutions of the diffusion equation. Monte Carlo approaches provide the additional advantage to be adaptable to any geometry, in particular more realistic head models. The goals of the present study were twofold: (1) to implement a fast and flexible Monte Carlo-based fitting routine to retrieve the brain optical properties; (2) to characterize the performances of this fitting method on realistic adult head data. We generated time-resolved data at various locations over the head, and fitted them with different models of light propagation: the homogeneous analytical model, and Monte Carlo simulations for three head models: a two-layer slab, the true subject's anatomy, and that of a generic atlas head. We found that the homogeneous model introduced a median 20 to 25% error on the recovered brain absorption, with large variations over the range of true optical properties. The two-layer slab model only improved moderately the results over the homogeneous one. On the other hand, using a generic atlas head registered to the subject's head surface decreased the error by a factor of 2. When the information is available, using the true subject anatomy offers the best performance. C1 [Selb, Juliette; Ogden, Tyler M.; Dubb, Jay; Fang, Qianqian; Boas, David A.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Opt Div, Charlestown, MA 02129 USA. RP Selb, J (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Opt Div, Bldg 149,13th St, Charlestown, MA 02129 USA. EM juliette@nmr.mgh.harvard.edu NR 28 TC 0 Z9 0 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-9347-7 J9 PROC SPIE PY 2013 VL 8578 AR 857817 DI 10.1117/12.2005323 PG 12 WC Biophysics; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biophysics; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BHU87 UT WOS:000326708600027 ER PT J AU Gale, JT Lee, KH Amirnovin, R Roberts, DW Williams, ZM Blaha, CD Eskandar, EN AF Gale, John T. Lee, Kendall H. Amirnovin, Ramin Roberts, David W. Williams, Ziv M. Blaha, Charles D. Eskandar, Emad N. TI Electrical Stimulation-Evoked Dopamine Release in the Primate Striatum SO STEREOTACTIC AND FUNCTIONAL NEUROSURGERY LA English DT Article DE Dopamine; Amperometry; Caudate; Basal Ganglia; Electrical Stimulation; Electrophysiology; Monkey ID CARBON-FIBER MICROELECTRODES; CENTRAL-NERVOUS-SYSTEM; PAVLOVIAN APPROACH BEHAVIOR; NUCLEUS-ACCUMBENS; NEURONAL-ACTIVITY; CELL-BODIES; REWARD; RAT; EXPECTATION; PERFORMANCE AB Background: Primate studies demonstrate that high-frequency electrical stimulation (HFS) of the caudate can enhance learning. Importantly, in these studies, stimulation was applied following the execution of behavior and the effect persisted into subsequent trials, suggesting a change in plasticity rather than a momentary facilitation of behavior. Objectives/Methods: Although the mechanism of HFS-enhanced learning is not understood, evidence suggests that dopamine plays a critical role. Therefore, we used in vivo amperometry to evaluate the effects of HFS on striatal dopamine release in the anesthetized primate. While this does not directly examine dopamine during learning, it provides insight with relation to dopamine dynamics during electrical stimulation and specifically between different stimulation parameters and striatal compartments. Results: We demonstrate that HFS results in significantly more dopamine release in the striatum compared to low-frequency stimulation. In addition, electrical stimulation operates differentially on specific neuronal elements, as the parameters for dopamine release are different for the caudate, putamen and medial forebrain bundle. Conclusions: While not direct evidence, these data suggest that HFS evokes significant dopamine release which may play a role in stimulation-enhanced learning. Moreover, these data suggest a means to modulate extracellular dopamine with a high degree of temporal and spatial precision for either research or clinical applications. (C) 2013 S. Karger AG, Basel C1 [Gale, John T.; Amirnovin, Ramin; Williams, Ziv M.; Eskandar, Emad N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA. [Gale, John T.; Amirnovin, Ramin; Williams, Ziv M.; Eskandar, Emad N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nayef Al Rodhan Labs Cellular Neurosurg & Neurosu, Boston, MA USA. [Lee, Kendall H.; Roberts, David W.] Dartmouth Med Sch, Dept Neurosurg, Lebanon, NH USA. [Blaha, Charles D.] Univ Memphis, Dept Psychol, Memphis, TN 38152 USA. RP Eskandar, EN (reprint author), Massachusetts Gen Hosp, Wang Ambulatory Care Ctr, 15 Parkman St, Boston, MA 02114 USA. EM eeskandar@partners.org OI Blaha, Charles/0000-0001-5155-1505 FU National Science Foundation [IOB 0645886]; National Institutes of Health [NEI 1R01EY017658-01A1, NIDA 1R01NS063249-01]; Howard Hughes Medical Institute FX This work was supported by grants from the National Science Foundation (IOB 0645886), the National Institutes of Health (NEI 1R01EY017658-01A1 and NIDA 1R01NS063249-01) and the Howard Hughes Medical Institute. NR 39 TC 11 Z9 11 U1 1 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1011-6125 EI 1423-0372 J9 STEREOT FUNCT NEUROS JI Stereotact. Funct. Neurosurg. PY 2013 VL 91 IS 6 BP 355 EP 363 DI 10.1159/000351523 PG 9 WC Neurosciences; Neuroimaging; Surgery SC Neurosciences & Neurology; Surgery GA 252ZT UT WOS:000327052100002 PM 24107983 ER PT S AU Lessing, D Anguera, MC Lee, JT AF Lessing, Derek Anguera, Montserrat C. Lee, Jeannie T. BE Chakravarti, A Green, E TI X Chromosome Inactivation and Epigenetic Responses to Cellular Reprogramming SO ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, VOL 14 SE Annual Review of Genomics and Human Genetics LA English DT Review; Book Chapter DE Xist; X chromosome reactivation; iPSC; ESC ID PLURIPOTENT STEM-CELLS; EMBRYONIC GERM-CELLS; HUMAN SOMATIC-CELLS; GROUND-STATE PLURIPOTENCY; EARLY MOUSE EMBRYOS; DOSAGE-COMPENSATION; GENE-EXPRESSION; RETT-SYNDROME; XIST RNA; DNA METHYLATION AB Reprogramming somatic cells to derive induced pluripotent stem cells (iPSCs) has provided a new method to model disease and holds great promise for regenerative medicine. Although genetically identical to their donor somatic cells, iPSCs undergo substantial changes in the epigenetic landscape during reprogramming. One such epigenetic process, X chromosome inactivation (XCI), has recently been shown to vary widely in human female iPSCs and embryonic stem cells (ESCs). XCI is a form of dosage compensation whose chief regulator is the noncoding RNA Xist. In mouse iPSCs and ESCs, Xist expression and XCI strictly correlate with the pluripotent state, but no such correlation exists in humans. Lack of XIST expression in human cells is linked to reduced developmental potential and an altered transcriptional profile, including upregulation of genes associated with cancer, which has therefore led to concerns about the safety of pluripotent stem cells for use in regenerative medicine. In this review, we describe how different states of XIST expression define three classes of female human pluripotent stem cells and explore progress in discovering the reasons for these variations and how they might be countered. C1 [Lessing, Derek] Harvard Univ, Sch Med, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Lessing, D (reprint author), Harvard Univ, Sch Med, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. EM lessing@molbio.mgh.harvard.edu; anguera@vet.upenn.edu; lee@molbio.mgh.harvard.edu NR 114 TC 36 Z9 38 U1 0 U2 19 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 1527-8204 BN 978-0-8243-3714-8 J9 ANNU REV GENOM HUM G JI Annu. Rev. Genomics Hum. Genet. PY 2013 VL 14 BP 85 EP 110 DI 10.1146/annurev-genom-091212-153530 PG 26 WC Genetics & Heredity SC Genetics & Heredity GA BHU05 UT WOS:000326658500005 PM 23662665 ER PT J AU Agasti, SS Laughney, AM Kohler, RH Weissleder, R AF Agasti, Sarit S. Laughney, Ashley M. Kohler, Rainer H. Weissleder, Ralph TI A photoactivatable drug-caged fluorophore conjugate allows direct quantification of intracellular drug transport SO CHEMICAL COMMUNICATIONS LA English DT Article ID MULTIDRUG-RESISTANCE; IN-VIVO; CELLS AB We report here a method that utilizes a photoactivatable drug-caged fluorophore conjugate to quantify intracellular drug trafficking processes at single cell resolution. Photoactivation is performed in labeled cellular compartments to visualize intracellular drug exchange under physiological conditions, without the need for washing, facilitating its translation into in vivo cancer models. C1 [Agasti, Sarit S.; Laughney, Ashley M.; Kohler, Rainer H.; Weissleder, Ralph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu FU NIH [P50CA086355, PO1-CA139980, R01CA164448, RO1EB010011] FX We thank Dr Katherine Yang for providing HT1080 cell lines and Jenna Klubnick for providing the PARPi derivative. We thank Dr Eunha Kim, Dr Jonathan Carlson and other colleagues in our laboratories for helpful advice and discussion. This research was supported in part by NIH grants P50CA086355, PO1-CA139980, R01CA164448 and RO1EB010011. NR 17 TC 5 Z9 5 U1 2 U2 22 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 EI 1364-548X J9 CHEM COMMUN JI Chem. Commun. PY 2013 VL 49 IS 94 BP 11050 EP 11052 DI 10.1039/c3cc46089d PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 248YQ UT WOS:000326742700011 PM 24135896 ER PT J AU Ballantyne, JC Carwood, C Gupta, A Bennett, MI Simpson, KH Dhandapani, K Lynch, L Baranidharan, G AF Ballantyne, Jane C. Carwood, Caroline Gupta, Anita Bennett, Michael I. Simpson, Karen H. Dhandapani, Karthikeyan Lynch, Louise Baranidharan, Ganesan TI Comparative efficacy of epidural, subarachnoid, and intracerebroventricular opioids in patients with pain due to cancer (Withdrawn Paper. 2013, art. no. CD005178) SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Correction C1 [Ballantyne, Jane C.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA. [Carwood, Caroline] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Gupta, Anita] Univ Penn, Philadelphia, PA 19104 USA. [Bennett, Michael I.] Univ Leeds, Leeds Inst Hlth Sci, Leeds, W Yorkshire, England. [Simpson, Karen H.] Leeds Teaching Hosp NHS Trust, Chron Pain Team, Leeds, W Yorkshire, England. [Dhandapani, Karthikeyan] Leeds Teaching Hosp, Seacroft Hosp, Leeds LS14 8UH, W Yorkshire, England. [Lynch, Louise] Leeds Teaching Hosp, Seacroft Hosp, Pain Clin, Leeds LS14 8UH, W Yorkshire, England. [Baranidharan, Ganesan] Leeds Teaching Hosp NHS Trust, Leeds, W Yorkshire, England. RP Dhandapani, K (reprint author), Leeds Teaching Hosp, Seacroft Hosp, York Rd, Leeds LS14 8UH, W Yorkshire, England. EM dkaarthik74@gmail.com NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1469-493X EI 1361-6137 J9 COCHRANE DB SYST REV JI Cochrane Database Syst Rev. PY 2013 IS 10 AR CD005178 DI 10.1002/14651858.CD005178.pub2 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 244FR UT WOS:000326373000035 PM 24163272 ER PT J AU Low, D Nguyen, DD Mizoguchi, E AF Low, Daren Nguyen, Deanna D. Mizoguchi, Emiko TI Animal models of ulcerative colitis and their application in drug research SO DRUG DESIGN DEVELOPMENT AND THERAPY LA English DT Review DE inflammatory bowel disease; preclinical trials; emerging therapy ID INFLAMMATORY-BOWEL-DISEASE; WISKOTT-ALDRICH-SYNDROME; PLACEBO-CONTROLLED TRIAL; INTESTINAL EPITHELIAL-CELLS; ACID-INDUCED COLITIS; MESENCHYMAL STEM-CELLS; RANDOMIZED CLINICAL-TRIAL; SODIUM-INDUCED COLITIS; CHAIN-DEFICIENT MICE; COTTON-TOP TAMARIN AB The specific pathogenesis underlying inflammatory bowel disease is complex, and it is even more difficult to decipher the pathophysiology to explain for the similarities and differences between two of its major subtypes, Crohn's disease and ulcerative colitis (UC). Animal models are indispensable to pry into mechanistic details that will facilitate better preclinical drug/therapy design to target specific components involved in the disease pathogenesis. This review focuses on common animal models that are particularly useful for the study of UC and its therapeutic strategy. Recent reports of the latest compounds, therapeutic strategies, and approaches tested on UC animal models are also discussed. C1 [Low, Daren; Nguyen, Deanna D.; Mizoguchi, Emiko] Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, Boston, MA 02114 USA. [Nguyen, Deanna D.; Mizoguchi, Emiko] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Mizoguchi, E (reprint author), Massachusetts Gen Hosp, GRJ 825D,55 Fruit St, Boston, MA 02114 USA. EM emizoguchi@partners.org FU National Institutes of Health (NIH) [DK80070, DK83430]; Eli and Edythe L Broad Medical Foundation; American Gastroenterological Association Foundation; Singapore A*STAR International Fellowship FX This work has been supported by the National Institutes of Health (NIH) (DK80070) and grants from the Eli and Edythe L Broad Medical Foundation and American Gastroenterological Association Foundation to EM and NIH DK83430 to DDN. DL has been awarded the Singapore A*STAR International Fellowship. NR 122 TC 33 Z9 34 U1 1 U2 17 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1177-8881 J9 DRUG DES DEV THER JI Drug Des. Dev. Ther. PY 2013 VL 7 BP 1341 EP 1356 DI 10.2147/DDDT.S40107 PG 16 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 250AT UT WOS:000326823200001 PM 24250223 ER PT J AU Luhar, RB Sawyer, KS Gravitz, Z Ruiz, SM Oscar-Berman, M AF Luhar, Riya B. Sawyer, Kayle S. Gravitz, Zoe Ruiz, Susan Mosher Oscar-Berman, Marlene TI Brain volumes and neuropsychological performance are related to current smoking and alcoholism history SO NEUROPSYCHIATRIC DISEASE AND TREATMENT LA English DT Article DE MRI; morphometry; neuropsychology; tobacco; alcohol ID CHRONIC CIGARETTE-SMOKING; HUMAN CEREBRAL-CORTEX; CARD SORTING TEST; COGNITIVE PERFORMANCE; GRAY-MATTER; FRONTAL-LOBE; VENTRAL PALLIDUM; CORPUS-CALLOSUM; TOBACCO USE; AGE 11 AB Background: Dual dependence on alcohol and nicotine is common, with many reports suggesting that more than 80% of alcoholics also smoke cigarettes. Even after cessation of alcohol consumption, many recovering alcoholics continue to smoke. In this exploratory study, we examined how current smoking and a history of alcoholism interacted in relation to brain volumes and neuropsychological performance. Methods: Participants were 14 abstinent long-term alcoholics (seven current smokers and seven nonsmokers), and 13 nonalcoholics (six current smokers and seven nonsmokers). The groups were equivalent in age, gender, education, and intelligence quotient. Two multiecho magnetization-prepared rapid acquisition with gradient echo (MP-RAGE) scans were collected for all participants using a 3T magnetic resonance imaging scanner with a 32 channel head coil. Brain volumes for each gray and white matter region of interest were derived using FreeSurfer. Participants completed a battery of neuropsychological tests measuring intelligence quotient, memory, executive functions, personality variables, and affect. Results: Compared to nonsmoking nonalcoholics, alcoholics who smoke (the comorbid group) had volumetric abnormalities in: pre- and para-central frontal cortical areas and rostral middle frontal white matter; parahippocampal and temporal pole regions; the amygdala; the pallidum; the ventral diencephalic region; and the lateral ventricle. The comorbid group performed worse than nonsmoking nonalcoholics on tests of executive functioning and on visually-based memory tests. History of alcoholism was associated with higher neuroticism scores among smokers, and current smoking was associated with higher sensation seeking scores and lower extraversion scores among nonalcoholics. Conclusion: Results from this exploratory study support and extend prior reports showing that alcoholism and smoking, alone and in combination, are associated with structural brain abnormalities and poorer performance on neuropsychological tests. Therefore, it is important to consider smoking status in alcoholism studies and vice versa. C1 [Luhar, Riya B.; Sawyer, Kayle S.; Gravitz, Zoe; Ruiz, Susan Mosher; Oscar-Berman, Marlene] Boston Healthcare Syst, US Dept Vet Affairs, Boston, MA USA. [Luhar, Riya B.; Sawyer, Kayle S.; Gravitz, Zoe; Ruiz, Susan Mosher; Oscar-Berman, Marlene] Boston Univ, Sch Med, Boston, MA 02118 USA. [Oscar-Berman, Marlene] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Oscar-Berman, M (reprint author), Boston Univ, Sch Med, Suite L-815,72 East Concord St, Boston, MA 02118 USA. EM oscar@bu.edu OI Sawyer, Kayle/0000-0001-7767-5688 FU National Institute on Alcohol Abuse and Alcoholism (NIAAA) [R01-AA007112, K05-AA000219]; Department of Veterans Affairs Medical Research Service; Center for Functional Neuroimaging Technologies [P41RR14075] FX This study was supported by funds from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) grants R01-AA007112 and K05-AA000219 to Dr Marlene Oscar Berman, and the Department of Veterans Affairs Medical Research Service, as well as the Center for Functional Neuroimaging Technologies, P41RR14075. The authors thank all research participants as well as Pooja Parikh, Diane Merritt, Mary M Valmas, and Steven Lehar, who assisted with recruitment, neuropsychological assessment, and MRI data collection. We also thank our collaborator Dr Gordon Harris who provided us mentorship at the Massachusetts General Hospital Athinoula A Martinos Center for Biomedical Imaging. NR 101 TC 13 Z9 13 U1 1 U2 16 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1176-6328 EI 1178-2021 J9 NEUROPSYCH DIS TREAT JI Neuropsychiatr. Dis. Treat. PY 2013 VL 9 BP 1767 EP 1784 DI 10.2147/NDT.S52298 PG 18 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 250BG UT WOS:000326824500002 PM 24273408 ER PT J AU Strouse, JJ Ivnitski-Steele, I Khawaja, HM Perez, D Ricci, J Yao, TL Weiner, WS Schroeder, CE Simpson, DS Maki, BE Li, KL Golden, JE Foutz, TD Waller, A Evangelisti, AM Young, SM Chavez, SE Garcia, MJ Ursu, O Bologa, CG Carter, MB Salas, VM Gouveia, K Tegos, GP Oprea, TI Edwards, BS Aube, J Larson, RS Sklar, LA AF Strouse, J. Jacob Ivnitski-Steele, Irena Khawaja, Hadya M. Perez, Dominique Ricci, Jerec Yao, Tuanli Weiner, Warren S. Schroeder, Chad E. Simpson, Denise S. Maki, Brooks E. Li, Kelin Golden, Jennifer E. Foutz, Terry D. Waller, Anna Evangelisti, Annette M. Young, Susan M. Chavez, Stephanie E. Garcia, Matthew J. Ursu, Oleg Bologa, Cristian G. Carter, Mark B. Salas, Virginia M. Gouveia, Kristine Tegos, George P. Oprea, Tudor I. Edwards, Bruce S. Aube, Jeffrey Larson, Richard S. Sklar, Larry A. TI A Selective ATP-Binding Cassette Subfamily G Member 2 Efflux Inhibitor Revealed via High-Throughput Flow Cytometry SO JOURNAL OF BIOMOLECULAR SCREENING LA English DT Article DE multidrug resistance; ABC transporter; ABCG2; ABCB1; efflux inhibition ID MEDIATED MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN INHIBITION; IN-VIVO REVERSAL; BREAST-CANCER; FUMITREMORGIN-C; POTENT MODULATOR; DRUG-RESISTANCE; CELL-LINES; CHEMOTHERAPY; VITRO AB Chemotherapeutics tumor resistance is a principal reason for treatment failure, and clinical and experimental data indicate that multidrug transporters such as ATP-binding cassette (ABC) B1 and ABCG2 play a leading role by preventing cytotoxic intracellular drug concentrations. Functional efflux inhibition of existing chemotherapeutics by these pumps continues to present a promising approach for treatment. A contributing factor to the failure of existing inhibitors in clinical applications is limited understanding of specific substrate/inhibitor/pump interactions. We have identified selective efflux inhibitors by profiling multiple ABC transporters against a library of small molecules to find molecular probes to further explore such interactions. In our primary screening protocol using JC-1 as a dual-pump fluorescent reporter substrate, we identified a piperazine-substituted pyrazolo[1,5-alpha]pyrimidine substructure with promise for selective efflux inhibition. As a result of a focused structure-activity relationship (SAR)-driven chemistry effort, we describe compound 1 (CID44640177), an efflux inhibitor with selectivity toward ABCG2 over ABCB1. Compound 1 is also shown to potentiate the activity of mitoxantrone in vitro as well as preliminarily in vivo in an ABCG2-overexpressing tumor model. At least two analogues significantly reduce tumor size in combination with the chemotherapeutic topotecan. To our knowledge, low nanomolar chemoreversal activity coupled with direct evidence of efflux inhibition for ABCG2 is unprecedented. C1 [Strouse, J. Jacob; Ivnitski-Steele, Irena; Perez, Dominique; Foutz, Terry D.; Waller, Anna; Evangelisti, Annette M.; Young, Susan M.; Chavez, Stephanie E.; Garcia, Matthew J.; Ursu, Oleg; Bologa, Cristian G.; Carter, Mark B.; Salas, Virginia M.; Gouveia, Kristine; Tegos, George P.; Oprea, Tudor I.; Edwards, Bruce S.; Sklar, Larry A.] Univ New Mexico, Ctr Mol Discovery, Albuquerque, NM 87131 USA. [Khawaja, Hadya M.; Ricci, Jerec; Tegos, George P.; Edwards, Bruce S.; Larson, Richard S.; Sklar, Larry A.] Univ New Mexico, Hlth Sci Ctr, Canc Res & Treatment Ctr, Dept Pathol, Albuquerque, NM 87131 USA. [Yao, Tuanli; Weiner, Warren S.; Schroeder, Chad E.; Simpson, Denise S.; Maki, Brooks E.; Li, Kelin; Golden, Jennifer E.; Aube, Jeffrey] Univ Kansas, Specialized Chem Ctr, Lawrence, KS 66045 USA. [Ursu, Oleg; Bologa, Cristian G.; Oprea, Tudor I.] Univ New Mexico, Sch Med, Dept Internal Med, Translat Informat Div, Albuquerque, NM 87131 USA. [Tegos, George P.] Harvard Univ, Sch Med, Dept Dermatol, Wellman Ctr Photomed,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Aube, Jeffrey] Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA. [Larson, Richard S.] Univ New Mexico, Hlth Sci Ctr, Res Off, Albuquerque, NM 87131 USA. RP Sklar, LA (reprint author), Univ New Mexico, Ctr Mol Discovery, 2325 Camino Salud NE,MSC07 4025, Albuquerque, NM 87131 USA. EM lsklar@salud.unm.edu RI Oprea, Tudor/A-5746-2011; Bologa, Cristian/A-7952-2010; OI Oprea, Tudor/0000-0002-6195-6976; Bologa, Cristian/0000-0003-2232-4244; Aube, Jeffrey/0000-0003-1049-5767; Golden, Jennifer/0000-0002-6813-3710 FU Nation Institutes of Health [U54MH084690, R03 MH081228-01A1, U54HG0050311] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Nation Institutes of Health grants U54MH084690 (LAS, UNMCMD), R03 MH081228-01A1 (RSL), and U54HG0050311 (JA, KU SCC). NR 33 TC 7 Z9 7 U1 1 U2 23 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0571 EI 1552-454X J9 J BIOMOL SCREEN JI J. Biomol. Screen PD JAN PY 2013 VL 18 IS 1 BP 26 EP 38 DI 10.1177/1087057112456875 PG 13 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry GA 059GT UT WOS:000312693100003 PM 22923785 ER PT J AU Jin, S Sarkar, KS Jin, YN Liu, Y Kokel, D Van Ham, TJ Roberts, LD Gerszten, RE MacRae, CA Peterson, RT AF Jin, Shan Sarkar, Kumar S. Jin, Youngnam N. Liu, Yan Kokel, David Van Ham, Tjakko J. Roberts, Lee D. Gerszten, Robert E. MacRae, Calum A. Peterson, Randall T. TI An In Vivo Zebrafish Screen Identifies Organophosphate Antidotes with Diverse Mechanisms of Action SO JOURNAL OF BIOMOLECULAR SCREENING LA English DT Article DE Xenopus; zebrafish; in vivo screening; mass spectrometry; high-content screening ID NERVE AGENTS; PESTICIDES; MODEL; RECEPTORS; OXIMES AB Organophosphates are a class of highly toxic chemicals that includes many pesticides and chemical weapons. Exposure to organophosphates, either through accidents or acts of terrorism, poses a significant risk to human health and safety. Existing antidotes, in use for over 50 years, have modest efficacy and undesirable toxicities. Therefore, discovering new organophosphate antidotes is a high priority. Early life stage zebrafish exposed to organophosphates exhibit several phenotypes that parallel the human response to organophosphates, including behavioral deficits, paralysis, and eventual death. Here, we have developed a high-throughput zebrafish screen in a 96-well plate format to find new antidotes that counteract organophosphate-induced lethality. In a pilot screen of 1200 known drugs, we identified 16 compounds that suppress organophosphate toxicity in zebrafish. Several in vitro assays coupled with liquid chromatography/tandem mass spectrometry-based metabolite profiling enabled determination of mechanisms of action for several of the antidotes, including reversible acetylcholinesterase inhibition, cholinergic receptor antagonism, and inhibition of bioactivation. Therefore, the in vivo screen is capable of discovering organophosphate antidotes that intervene in distinct pathways. These findings suggest that zebrafish screens might be a broadly applicable approach for discovering compounds that counteract the toxic effects of accidental or malicious poisonous exposures. C1 [Jin, Shan; Sarkar, Kumar S.; Jin, Youngnam N.; Liu, Yan; Kokel, David; Van Ham, Tjakko J.; Roberts, Lee D.; Gerszten, Robert E.; Peterson, Randall T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Charlestown, MA 02129 USA. [Jin, Shan; Sarkar, Kumar S.; Jin, Youngnam N.; Liu, Yan; Kokel, David; Van Ham, Tjakko J.; Roberts, Lee D.; Gerszten, Robert E.; MacRae, Calum A.; Peterson, Randall T.] Broad Inst, Cambridge, MA USA. [MacRae, Calum A.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Peterson, RT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, 149 13th St, Charlestown, MA 02129 USA. EM peterson@cvrc.mgh.harvard.edu RI van Ham, Tjakko/I-2382-2013; van Ham, Tjakko/A-1989-2015; OI van Ham, Tjakko/0000-0002-2175-8713; Roberts, Lee/0000-0002-1455-5248 FU Office of the Director, National Institutes of Health (OD); National Institute of Neurological Disorders and Stroke (NINDS) [U01 NS063733] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Supported by the CounterACT Program, Office of the Director, National Institutes of Health (OD) and the National Institute of Neurological Disorders and Stroke (NINDS), Grant Number U01 NS063733 to RTP. NR 24 TC 9 Z9 10 U1 0 U2 22 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0571 EI 1552-454X J9 J BIOMOL SCREEN JI J. Biomol. Screen PD JAN PY 2013 VL 18 IS 1 BP 108 EP 115 DI 10.1177/1087057112458153 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry GA 059GT UT WOS:000312693100010 PM 22960781 ER PT J AU Bogdanova, Y Cronin-Golomb, A AF Bogdanova, Yelena Cronin-Golomb, Alice TI Alexithymia and apathy in Parkinson's disease: Neurocognitive correlates SO BEHAVIOURAL NEUROLOGY LA English DT Article DE Non-motor symptoms; basal ganglia; ACC; frontostriatal; right hemisphere ID DEPRESSIVE SYMPTOMS; CORTICAL ACTIVATION; TORONTO-ALEXITHYMIA; CIRCUITS; PREVALENCE; VALIDITY; BEHAVIOR; ILLNESS; ASSOCIATION; RELIABILITY AB Non-motor symptoms such as neuropsychiatric and cognitive dysfunction have been found to be common in Parkinson's disease (PD) but the relation between such symptoms is poorly understood. We focused on alexithymia, an impairment of affective and cognitive emotional processing, as there is evidence for its interaction with cognition in other disorders. Twenty-two non-demented PD patients and 22 matched normal control adults (NC) were administered rating scales assessing neuropsychiatric status, including alexithymia, apathy, and depression, and a series of neuropsychological tests. As expected, PD patients showed more alexithymia than NC, and there was a significant association between alexithymia and disease stage. Alexithymia was associated with performance on non-verbally mediated measures of executive and visuospatial function, but not on verbally mediated tasks. By contrast, there was no correlation between cognition and ratings of either depression or apathy. Our findings demonstrate a distinct association of alexithymia with non-verbal cognition in PD, implicating right hemisphere processes, and differentiate between alexithymia and other neuropsychiatric symptoms in regard to PD cognition. C1 [Bogdanova, Yelena] VA Boston Healthcare Syst, Psychol Res, Boston, MA 02130 USA. [Bogdanova, Yelena; Cronin-Golomb, Alice] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Bogdanova, Yelena] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Bogdanova, Yelena] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Bogdanova, Y (reprint author), VA Boston Healthcare Syst, Psychol Res 151A, 150 South Huntington Ave, Boston, MA 02130 USA. EM bogdanov@bu.edu FU Rehabilitation Research and Development Service of the Department of Veterans Affairs; National Institute of Neurological Disorders and Stroke [R01NS067128, R21 NS043730]; [NIH F31 NS052131] FX This work was supported in part by the Rehabilitation Research and Development Service of the Department of Veterans Affairs, and by grants to Y. Bogdanova (NIH F31 NS052131) and A. Cronin-Golomb (R01NS067128 and R21 NS043730) from the National Institute of Neurological Disorders and Stroke. We thank Dr. Sandy Neargarder for expert advice on statistical analyses; Mirella Diaz-Santos, M. A., and Maria Valmas, M. A., for assistance with data collection; and Sarah M. Kark, B. S., for assistance with manuscript preparation. The authors have no conflicts of interest to disclose. NR 89 TC 8 Z9 8 U1 4 U2 12 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0953-4180 EI 1875-8584 J9 BEHAV NEUROL JI Behav. Neurol. PY 2013 VL 27 IS 4 BP 535 EP 545 DI 10.3233/BEN-129021 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 245KV UT WOS:000326463500008 PM 23242364 ER PT J AU Rosendorff, C AF Rosendorff, C. TI Treatment of hypertension with CAD: AHA guidelines SO CARDIOLOGY LA English DT Meeting Abstract C1 [Rosendorff, C.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY USA. [Rosendorff, C.] James J Peters VA Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2013 VL 126 SU 2 BP 240 EP 240 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 245CR UT WOS:000326437200234 ER PT J AU Thase, ME AF Thase, Michael E. TI The Multifactorial Presentation of Depression in Acute Care SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID SEASONAL AFFECTIVE-DISORDER; STAR-ASTERISK-D; BEHAVIORAL-ANALYSIS SYSTEM; MAJOR DEPRESSION; NONANXIOUS DEPRESSION; ATYPICAL DEPRESSION; UNIPOLAR DEPRESSION; PREVALENCE; FEATURES; BIPOLAR AB Depression is by its very nature a heterogeneous disorder; 2 patients with the same diagnosis (ie, major depressive disorder) may have few symptoms in common. This heterogeneity is evidenced by the fact that depression presents in a wide variety forms related to polarity (unipolar vs bipolar), symptoms (melancholic, atypical, psychotic, or anxious), onset (specific events, seasons, or age), recurrence, and severity. These diagnostic specifiers and subgroups can guide treatment decisions in several ways. For example, recognizing a specific depressive subtype in a patient can help the clinician select an appropriate treatment based on that patient's particular presentation. These subtypes can also guide treatment by helping the clinician and patient to identify and discuss factors that help or hinder the achievement of remission and recovery. Although depression specifiers and subtypes are subject to revision and change, many of them provide helpful information about recognition and treatment. C1 [Thase, Michael E.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Thase, Michael E.] Univ Penn, Dept Psychiat, Sch Med, Philadelphia Vet Affairs Med Ctr, Pittsburgh, PA USA. [Thase, Michael E.] Univ Pittsburgh, Med Ctr, Dept Psychiat, Philadelphia, PA USA. [Thase, Michael E.] Univ Pittsburgh, Dept Psychiat, Med Ctr, Pittsburgh, PA USA. RP Thase, ME (reprint author), 3535 Market St,Ste 670, Philadelphia, PA 19104 USA. EM thase@mail.med.upenn.edu FU AHRQ Eli Lilly; Forest; NIMH; Otsuka FX Dr Thase is an advisor/consultant for Alkermes, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Dey, Forest, Gerson Lehman, GlaxoSmithKline, Guidepoint Global, Lundbeck, MedAvante, Merck, Neuronetics, Ortho-McNeil, Otsuka, Pamlab, Pfizer, Roche, Shire, Sunovion, Takeda, and Transcept; has received grant/research support from AHRQ Eli Lilly, Forest, NIMH, and Otsuka; has received honoraria from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck, and Pfizer; has equity holdings in MedAvante; and has received royalties from the American Psychiatric Foundation, Guilford Publications, Herald House, and W.W. Norton & Company; his spouse/partner is employed by Peloton Advantage. NR 43 TC 3 Z9 3 U1 0 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 2013 VL 74 SU 2 BP 3 EP 8 DI 10.4088/JCP.12084su1c.01 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 243KV UT WOS:000326316200001 PM 24191971 ER PT J AU Qi, W Ghoroghchian, PP Li, GZ Hammer, DA Therien, MJ AF Qi, Wei Ghoroghchian, P. Peter Li, Guizhi Hammer, Daniel A. Therien, Michael J. TI Aqueous self-assembly of poly(ethylene oxide)-block-poly(epsilon-caprolactone) (PEO-b-PCL) copolymers: disparate diblock copolymer compositions give rise to nano- and meso-scale bilayered vesicles SO NANOSCALE LA English DT Article ID INFRARED-EMISSIVE POLYMERSOMES; BLOCK-COPOLYMERS; IN-VIVO; MOLECULAR-WEIGHT; BIODEGRADABLE POLYMERSOMES; STANNOUS OCTOATE; POLYMERIZATION; DELIVERY; OXIDE); MORPHOLOGIES AB Nanoparticles formed from diblock copolymers of FDA approved PEO and PCL have generated considerable interest as in vivo drug delivery vehicles. Herein, we report the synthesis of the most extensive family PEO-b-PCL copolymers that vary over the largest range of number-average molecular weights (M-n: 3.6-57k), PEO weight fractions (f(PEO): 0.08-0.33), and PEO chain lengths (0.75-5.8k) reported to date. These polymers were synthesized in order to establish the full range of aqueous phase behaviours of these diblock copolymers and to specifically identify formulations that were able to generate bilayered vesicles (polymersomes). Cryogenic transmission electron microscopy (cryo-TEM) was utilized in order to visualize the morphology of these structures upon aqueous self-assembly of dry polymer films. Nanoscale polymersomes were formed from PEO-b-PCL copolymers over a wide range of PEO weight fractions (f(PEO): 0.14-0.27) and PEO molecular weights (0.75-3.8k) after extrusion of aqueous suspensions. Comparative morphology diagrams, which describe the nature of self-assembled structures as a function of diblock copolymer molecular weight and PEO weight fraction, show that in contrast to micron-scale polymersomes, which form only from a limited range of PEO-b-PCL diblock copolymer compositions, a multiplicity of PEO-b-PCL diblock copolymer compositions are able to give rise to nanoscale vesicles. These data underscore that PEO-b-PCL compositions that spontaneously form micron-sized polymersomes, as well as those that have previously been reported to form polymersomes via a cosolvent fabrication system, provide only limited insights into the distribution of PEO-b-PCL diblocks that give rise to nanoscale vesicles. The broad range of polymersome-forming PEO-b-PCL compositions described herein suggest the ability to construct extensive families of nanoscale vesicles of varied bilayer thickness, providing the ability to tune the timescales of vesicle degradation and encapsulant release based on the intended in vivo application. C1 [Qi, Wei; Therien, Michael J.] Duke Univ, Dept Chem, French Family Sci Ctr, Durham, NC 27708 USA. [Qi, Wei; Li, Guizhi] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. [Ghoroghchian, P. Peter] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hammer, Daniel A.] Univ Penn, Sch Engn & Appl Sci, Dept Bioengn, Philadelphia, PA 19104 USA. RP Therien, MJ (reprint author), Duke Univ, Dept Chem, French Family Sci Ctr, 124 Sci Dr, Durham, NC 27708 USA. EM michael.therien@duke.edu FU Department of Defense [W81XWH-13-1-0086]; National Cancer Institute [R01CA115229]; National Institutes of Health [EB003457-01]; MRSEC Program of the National Science Foundation [DMR-00-79909] FX This work was supported by grants from the Department of Defense (W81XWH-13-1-0086), the National Cancer Institute (R01CA115229), and the National Institutes of Health (EB003457-01). M.J.T. and D.A.H. thank the MRSEC Program of the National Science Foundation (DMR-00-79909) for infrastructural support. NR 57 TC 22 Z9 22 U1 7 U2 87 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-3364 EI 2040-3372 J9 NANOSCALE JI Nanoscale PY 2013 VL 5 IS 22 BP 10908 EP 10915 DI 10.1039/c3nr03250g PG 8 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 242GD UT WOS:000326225500026 PM 24056924 ER PT J AU McFarland, NR Burdett, T Desjardins, CA Frosch, MP Schwarzschild, MA AF McFarland, Nikolaus R. Burdett, Thomas Desjardins, Cody A. Frosch, Matthew P. Schwarzschild, Michael A. TI Postmortem Brain Levels of Urate and Precursors in Parkinson's Disease and Related Disorders SO NEURODEGENERATIVE DISEASES LA English DT Article DE Uric acid; Purines; Neurodegeneration; Parkinsonism; Lewy body disease; Alzheimer's disease ID SERUM URIC-ACID; MILD COGNITIVE IMPAIRMENT; PLASMA URATE; DIAGNOSTIC-CRITERIA; ALZHEIMERS-DISEASE; RISK; PROGRESSION; DEMENTIA; ANTIOXIDANTS; PREDICTOR AB Background: Increasing evidence suggests that urate may play an important role in neurodegenerative disease. In Parkinson's disease (PD) higher, but still normal, levels of blood and cerebrospinal fluid urate have been associated with a lower rate of disease progression. Objective: We explored the hypothesis that lower levels of urate and its purine precursors in brain may be associated with PD and related neurodegenerative disorders, including Alzheimer's disease (AD) and Lewy body dementia (DLB). Methods: Human postmortem brain tissues were obtained from PD, AD, and DLB patients and non-neurodegenerative disease controls. We measured urate and other purine pathway analytes in the frontal and temporal cortex, striatum, and cerebellum, using high-performance liquid chromatography with electrochemical and ultraviolet detection. Results: Age was wellmatched among groups. Mean postmortem interval for samples was 16.3 9.9 h. Urate levels in cortical and striatal tissue trended lower in PD and AD compared to controls in males only. These findings correlated with increased urate in male versus female control tissues. By contrast, in DLB urate levels were significantly elevated relative to PD and AD. Measurement of urate precursors suggested a decrease in xanthine in PD compared to AD in females only, and relative increases in inosine and adenosine in DLB and AD samples among males. Xanthine and hypoxanthine were more concentrated in striatal tissue than in other brain regions. Conclusions: Though limited in sample size, these findings lend support to the inverse association between urate levels and PD, as well as possibly AD. The finding of increased urate in DLB brain tissue is novel and warrants further study. copyright (C) 2013 S.Karger AG, Basel C1 [McFarland, Nikolaus R.] Univ Florida, Coll Med, Dept Neurol, Ctr Translat Res Neurodegenerat Dis, Gainesville, FL 32610 USA. [McFarland, Nikolaus R.; Burdett, Thomas; Desjardins, Cody A.; Frosch, Matthew P.; Schwarzschild, Michael A.] Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Boston, MA 02114 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP McFarland, NR (reprint author), Univ Florida, 1275 Ctr Dr,BMS J489,POB 100159, Gainesville, FL 32610 USA. EM nikolaus.mcfarland@neurology.ufl.edu OI McFarland, Nikolaus/0000-0002-8699-8857 FU Harvard NeuroDiscovery Center [NIH K08NS067024, NIH K24NS060991, W81XWH-11-1-0150]; RJG Foundation FX Special thanks to Karlotta Fitch and Miriam Greenstein for help with brain tissue samples. This study was supported by the Harvard NeuroDiscovery Center, NIH K08NS067024 (N.R.M.), NIH K24NS060991, DoD W81XWH-11-1-0150, and the RJG Foundation. NR 41 TC 3 Z9 4 U1 2 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-2854 EI 1660-2862 J9 NEURODEGENER DIS JI Neurodegener. Dis. PY 2013 VL 12 IS 4 BP 189 EP 198 DI 10.1159/000346370 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 243LL UT WOS:000326317800003 PM 23467193 ER EF