FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Jun, D Ghaznavi, Z Ryden, AM Warner, AL Zeidler, MR AF Jun, D. Ghaznavi, Z. Ryden, A. M. Warner, A. L. Zeidler, M. R. TI Sleep Disordered Breathing In Hospitalized Va Heart Failure Patients SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Jun, D.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Ghaznavi, Z.; Ryden, A. M.; Warner, A. L.; Zeidler, M. R.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Ghaznavi, Z.; Warner, A. L.] West Lost Angeles VA Med Ctr, Los Angeles, CA USA. [Ryden, A. M.; Zeidler, M. R.] West Los Angeles VA Med Ctr, Los Angeles, CA USA. EM dale.jun@cshs.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A1245 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582800244 ER PT J AU Karamooz, E Harriff, M Grant, WF Canfield, ET Burr, A Moita, LF Lewinsohn, DM AF Karamooz, E. Harriff, M. Grant, W. F. Canfield, E. T. Burr, A. Moita, L. F. Lewinsohn, D. M. TI Key Role For Vamp4 In Mr1 Dependent Presentation Of Mycobacterial Antigen To Mait Cells SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Karamooz, E.; Grant, W. F.; Canfield, E. T.; Lewinsohn, D. M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Harriff, M.; Burr, A.] Portland VA Med Ctr, Portland, OR USA. [Moita, L. F.] Inst Mol Med, Lisbon, Portugal. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A2183 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582801575 ER PT J AU Kelly, VJ Winkler, T Hibbert, KA Kone, M Greenblatt, EE Kohli, P Venegas, JG Harris, RS AF Kelly, V. J. Winkler, T. Hibbert, K. A. Kone, M. Greenblatt, E. E. Kohli, P. Venegas, J. G. Harris, R. S. TI Ventilation Defects Persist At Elevated Lung Volumes In Some Patients With Asthma But Not Others SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Kelly, V. J.; Winkler, T.; Hibbert, K. A.; Kone, M.; Greenblatt, E. E.; Kohli, P.; Venegas, J. G.; Harris, R. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kelly, V. J.; Winkler, T.; Hibbert, K. A.; Kohli, P.; Venegas, J. G.; Harris, R. S.] Harvard Univ, Sch Med, Boston, MA USA. [Greenblatt, E. E.] MIT, Boston, MA USA. EM vanessajanekelly@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A1212 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582800211 ER PT J AU Kim, V Anzueto, A Han, MK Martinez, CH Black-Shinn, JL Boriek, A Porszacz, J Soler, X Wise, RA Dass, C Comellas, AP Ramsdell, JW Criner, GJ Sharafkhaneh, A Yen, A Crapo, J Make, BJ Silverman, EK Curtis, JL AF Kim, V. Anzueto, A. Han, M. K. Martinez, C. H. Black-Shinn, J. L. Boriek, A. Porszacz, J. Soler, X. Wise, R. A. Dass, C. Comellas, A. P. Ramsdell, J. W. Criner, G. J. Sharafkhaneh, A. Yen, A. Crapo, J. Make, B. J. Silverman, E. K. Curtis, J. L. CA COPDGene Investigators TI Persistent And Newly Developed Chronic Bronchitis Is Associated With Worse Outcomes And Increased Respiratory Symptoms In Smokers With And Without Chronic Obstructive Pulmonary Disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Kim, V.; Dass, C.; Criner, G. J.] Temple Univ, Sch Med, Philadelphia, PA 19122 USA. [Anzueto, A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Anzueto, A.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Han, M. K.; Martinez, C. H.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Black-Shinn, J. L.] Univ Colorado, Colorado Sch Publ Hlth, Aurora, CO USA. [Boriek, A.; Sharafkhaneh, A.] Baylor Coll Med, Houston, TX 77030 USA. [Porszacz, J.] Harbor UCLA Med Ctr, Loas Angeles Biomed Res Inst, Torrance, CA 90509 USA. [Soler, X.; Ramsdell, J. W.; Yen, A.] Univ Calif San Diego, San Diego, CA 92103 USA. [Wise, R. A.] Johns Hopkins Med Ctr, Baltimore, MD USA. [Comellas, A. P.] Univ Iowa, Iowa City, IA USA. [Crapo, J.; Make, B. J.] Natl Jewish Hlth, Denver, CO USA. [Silverman, E. K.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Curtis, J. L.] Univ Michigan, VA Med Ctr, Ann Arbor, MI 48109 USA. EM victor.kim@tuhs.temple.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A2854 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582803098 ER PT J AU Kinney, GL Darabian, S Jacobs, MR Lambert, AA Black-Shinn, JL Anzueto, A Bon, J Boriek, AM Bowler, RP Dass, C Demeo, DL Foreman, MG Hoffman, EA Kim, V Li, D Parulekar, AD Van Beek, E Yen, A Wise, RA Curtis, JL Newell, JD Hokanson, JE Make, BJ Washko, GR Rossiter, HB Casaburi, R Rennard, SI McDonald, MLN AF Kinney, G. L. Darabian, S. Jacobs, M. R. Lambert, A. A. Black-Shinn, J. L. Anzueto, A. Bon, J. Boriek, A. M. Bowler, R. P. Dass, C. DeMeo, D. L. Foreman, M. G. Hoffman, E. A. Kim, V. Li, D. Parulekar, A. D. Van Beek, E. Yen, A. Wise, R. A. Curtis, J. L. Newell, J. D. Hokanson, J. E. Make, B. J. Washko, G. R. Rossiter, H. B. Casaburi, R. Rennard, S. I. McDonald, M. -L. N. TI Determinants Of 5-Year Change In BMI In Current And Former Smokers SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Kinney, G. L.] Colorado Sch Publ Hlth, Aurora, CO USA. [Darabian, S.] LABiomed, Torrance, CA USA. [Jacobs, M. R.; Dass, C.] Temple Univ, Philadelphia, PA 19122 USA. [Lambert, A. A.] Johns Hopkins Univ, Baltimore, MD USA. [Black-Shinn, J. L.] Univ Colorado, Colorado Sch Publ Hlth, Aurora, CO USA. [Anzueto, A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Anzueto, A.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Bon, J.] Univ Pittsburgh, Pittsburgh, PA USA. [Boriek, A. M.] Baylor Coll Med, Houston, TX 77030 USA. [Bowler, R. P.] Natl Jewish Hlth & Res Ctr, Denver, CO USA. [DeMeo, D. L.; Washko, G. R.; McDonald, M. -L. N.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Foreman, M. G.] Morehouse Sch Med, Atlanta, GA 30310 USA. [Hoffman, E. A.] Univ Iowa, Carver Coll Med, Iowa City, IA USA. [Kim, V.] Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. [Li, D.] Los Angeles Biomed Res Inst, Torrance, CA USA. [Parulekar, A. D.] Baylor Coll Med, Houston, TX 77030 USA. [Van Beek, E.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Yen, A.] Univ Calif San Diego, San Diego, CA USA. [Wise, R. A.] Johns Hopkins Med Ctr, Baltimore, MD USA. [Curtis, J. L.] Univ Michigan, VA Med Ctr, Ann Arbor, MI 48109 USA. [Newell, J. D.] Univ Iowa, Iowa City, IA USA. [Hokanson, J. E.] Univ Colorado, Denver, CO 80202 USA. [Make, B. J.] Natl Jewish Hlth, Denver, CO USA. [Rossiter, H. B.] Harbor ULCA Med Ctr, Los Angeles Biomed Res Inst, Torrance, CA USA. [Casaburi, R.] Harbor UCLA Med Ctr, Torrance, CA USA. [Rennard, S. I.] Univ Nebraska, Omaha, NE 68182 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A5702 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582807563 ER PT J AU Knipe, RS Liao, JK Tager, AM AF Knipe, R. S. Liao, J. K. Tager, A. M. TI Differing Requirements For The Rock Isoforms Rock 1 And Rock 2 For Epithelial Cell Apoptosis And Fibroblast Migration In Pulmonary Fibrosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Knipe, R. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Liao, J. K.] Univ Chicago, Chicago, IL 60637 USA. [Tager, A. M.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A5336 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582807155 ER PT J AU Kohli, P Neilan, T Natarajan, P Kwong, R Malhotra, A Celli, BR Harris, RS AF Kohli, P. Neilan, T. Natarajan, P. Kwong, R. Malhotra, A. Celli, B. R. Harris, R. S. TI Effect Of Inhaler Therapy On Cardiac Performance In Individuals With COPD And Heart Disease: A Pilot Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Kohli, P.; Harris, R. S.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Kohli, P.; Neilan, T.; Natarajan, P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kwong, R.; Celli, B. R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Malhotra, A.] Univ Calif San Diego, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A5714 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582807575 ER PT J AU Kohli, P Rodriguez-Lopez, J Kelly, VJ Gladysheva, E Witkin, AS Winkler, T Kone, M Greenblatt, EE Hibbert, KA Channick, RN Harris, RS AF Kohli, P. Rodriguez-Lopez, J. Kelly, V. J. Gladysheva, E. Witkin, A. S. Winkler, T. Kone, M. Greenblatt, E. E. Hibbert, K. A. Channick, R. N. Harris, R. S. TI Chronic Thromboembolic Pulmonary Hypertension: Predicting Who Will Benefit From Pulmonary Thromboendarterectomy Using Functional Imaging SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Kohli, P.; Rodriguez-Lopez, J.; Kelly, V. J.; Witkin, A. S.; Winkler, T.; Kone, M.; Greenblatt, E. E.; Hibbert, K. A.; Channick, R. N.; Harris, R. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gladysheva, E.] Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A4833 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582806267 ER PT J AU Kohli, P Kelly, VJ Winkler, T Kone, M Greenblatt, EE Hibbert, KA Corleis, B Cho, JL Medoff, BD Kwon, DS Harris, RS AF Kohli, P. Kelly, V. J. Winkler, T. Kone, M. Greenblatt, E. E. Hibbert, K. A. Corleis, B. Cho, J. L. Medoff, B. D. Kwon, D. S. Harris, R. S. TI Hiv Infection And COPD: The Use Of Functional Pet Imaging To Determine Early Pulmonary Physiologic Changes In Susceptible Individuals SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Kohli, P.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Kelly, V. J.; Winkler, T.; Greenblatt, E. E.; Hibbert, K. A.; Cho, J. L.; Medoff, B. D.; Kwon, D. S.; Harris, R. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kelly, V. J.; Harris, R. S.] Harvard Univ, Sch Med, Boston, MA USA. [Corleis, B.; Kwon, D. S.] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A4714 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582806149 ER PT J AU Lagares, D Liu, F Auernheimer, V Adams, DC Ludovic, V Kapoor, M Suter, MJ Goldmann, W Engler, AJ Tschumperlin, DJ Tager, AM AF Lagares, D. Liu, F. Auernheimer, V. Adams, D. C. Ludovic, V. Kapoor, M. Suter, M. J. Goldmann, W. Engler, A. J. Tschumperlin, D. J. Tager, A. M. TI Feedback Amplification Of Lung Fibrosis Through Matrix Stiffness Gradient-Induced Fibroblast Durotaxis Via alpha tat1-Mediated Microtubule Acetylation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Lagares, D.; Tager, A. M.] Massachusetts Gen Hosp, Charlestown, MA USA. [Liu, F.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Auernheimer, V.; Goldmann, W.] Univ Erlangen Nurnberg, Ctr Med Phys & Technol, D-91054 Erlangen, Germany. [Adams, D. C.; Suter, M. J.] Harvard Univ, Sch Med, Boston, MA USA. [Adams, D. C.; Suter, M. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ludovic, V.; Engler, A. J.] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. [Kapoor, M.] Toronto Western Res Inst, Toronto, ON, Canada. [Tschumperlin, D. J.] Mayo Clin, Rochester, MN USA. EM dlagares@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A5329 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582807148 ER PT J AU Lai, PS Araki, T Hang, JQ Zhang, FY Sun, J Su, L Washko, GR Nishino, M Hatabu, H Christiani, DC AF Lai, P. S. Araki, T. Hang, J. -Q. Zhang, F. -Y. Sun, J. Su, L. Washko, G. R. Nishino, M. Hatabu, H. Christiani, D. C. TI Occupational Endotoxin Exposure Is Associated With Decreased Interstitial Lung Abnormalities SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Lai, P. S.; Su, L.; Christiani, D. C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Lai, P. S.; Araki, T.; Washko, G. R.; Hatabu, H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hang, J. -Q.; Zhang, F. -Y.; Sun, J.] Shanghai Putuo Dist Peoples Hosp, Shanghai, Peoples R China. [Nishino, M.] Dana Farber Canc Ctr, Boston, MA USA. EM pslai@hsph.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A2572 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582802426 ER PT J AU Lamas, D Owens, R Massaro, A Nace, RN Bernacki, R Block, S AF Lamas, D. Owens, R. Massaro, A. Nace, R. N. Bernacki, R. Block, S. TI Giving Voice To An Invisible Population: A Pilot Study Of A Communication Guide For Chronically Critically Ill Patients In A Long-Term Acute Care Hospital SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Lamas, D.; Massaro, A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Owens, R.] Univ Calif San Diego, San Diego, CA 92103 USA. [Nace, R. N.] Spaulding Hosp, Cambridge, MA USA. [Bernacki, R.; Block, S.] Dana Farber Canc Inst, Boston, MA 02115 USA. EM dlamas@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A3914 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582804581 ER PT J AU Lin, VY Raju, S Birket, SE Liu, L Shastry, S Mazur, M Chu, KK Tearney, GJ Rowe, SM AF Lin, V. Y. Raju, S. Birket, S. E. Liu, L. Shastry, S. Mazur, M. Chu, K. K. Tearney, G. J. Rowe, S. M. TI Cftr Potentiator Ivacaftor, A Novel Mucus Clearance Therapy In COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Lin, V. Y.; Raju, S.; Birket, S. E.; Shastry, S.; Mazur, M.; Rowe, S. M.] Univ Alabama Birmingham, Birmingham, AL USA. [Liu, L.] Nanyang Technol Univ, Singapore 639798, Singapore. [Chu, K. K.; Tearney, G. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chu, K. K.; Tearney, G. J.] Harvard Univ, Sch Med, Boston, MA USA. EM vivbot@uab.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A3871 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582804513 ER PT J AU Liu, Y Iannone, O Lear, T Chen, BB Mallampalli, RK AF Liu, Y. Iannone, O. Lear, T. Chen, B. B. Mallampalli, R. K. TI Pro-Apoptotic F-Box Protein Fbxl7 Regulates Mitochondrial Function By Mediating The Ubiquitylation And Proteasomal Degradation Of Survivin SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Liu, Y.; Iannone, O.; Lear, T.; Chen, B. B.] Univ Pittsburgh, Pittsburgh, PA USA. [Mallampalli, R. K.] Vet Affairs Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA USA. EM yul119@pitt.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A5554 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582807415 ER PT J AU Lv, N Blonstein, AC Camargo, CA Wilson, SR Buist, S Lavori, P Strub, P Nadeau, KC Xiao, L Rosas, LG Ma, J AF Lv, N. Blonstein, A. C. Camargo, C. A. Wilson, S. R. Buist, S. Lavori, P. Strub, P. Nadeau, K. C. Xiao, L. Rosas, L. G. Ma, J. TI Process Evaluation Of The "dash For Asthma" Intervention In A Randomized Controlled Trial Pilot Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Lv, N.; Blonstein, A. C.; Wilson, S. R.; Rosas, L. G.; Ma, J.] Palo Alto Med Fdn, Res Inst, Palo Alto, CA 94301 USA. [Camargo, C. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Buist, S.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Lavori, P.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Strub, P.] Permanente Med Grp Inc, San Francisco, CA USA. [Nadeau, K. C.] Stanford Univ, Stanford, CA 94305 USA. [Xiao, L.] Palo Alto Med Fdn, Palo Alto, CA USA. EM lvn@pamfri.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A1715 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582801114 ER PT J AU Ma, J Xiao, L Lv, N Camargo, CA Wilson, SR Buist, S Lavori, P Strub, P Nadeau, KC Rosas, LG AF Ma, J. Xiao, L. Lv, N. Camargo, C. A. Wilson, S. R. Buist, S. Lavori, P. Strub, P. Nadeau, K. C. Rosas, L. G. TI Randomized Trial Of Healthy Eating Pattern In Adults With Uncontrolled Asthma SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Ma, J.; Xiao, L.; Lv, N.; Wilson, S. R.; Rosas, L. G.] Palo Alto Med Fdn, Res Inst, Palo Alto, CA 94301 USA. [Camargo, C. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Buist, S.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Lavori, P.] Stanford Univ, Sch Med, Stanford, CA USA. [Strub, P.] Permanente Med Grp Inc, San Francisco, CA USA. [Nadeau, K. C.] Stanford Univ, Stanford, CA 94305 USA. EM lvn@pamfri.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A5401 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582807269 ER PT J AU Maltz, LA Matz, E Gordish-Dressman, H Pillai, DK Teach, SJ Camargo, C Hubal, M Behniwal, SK Prosper, D Certner, N Marwah, R Mansell, DM Nwachuku, F Lazaroff, R Tsegaye, Y Freishtat, RJ AF Maltz, L. A. Matz, E. Gordish-Dressman, H. Pillai, D. K. Teach, S. J. Camargo, C. Hubal, M. Behniwal, S. K. Prosper, D. Certner, N. Marwah, R. Mansell, D. M. Nwachuku, F. Lazaroff, R. Tsegaye, Y. Freishtat, R. J. TI Larger Neck Circumference Is Associated With Poor Asthma Control In Obese Youth SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Maltz, L. A.; Matz, E.; Gordish-Dressman, H.; Pillai, D. K.; Teach, S. J.; Hubal, M.; Behniwal, S. K.; Prosper, D.; Certner, N.; Marwah, R.; Mansell, D. M.; Nwachuku, F.; Lazaroff, R.; Tsegaye, Y.; Freishtat, R. J.] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Camargo, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A3368 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582804019 ER PT J AU Maron, BA Hess, E Opotowsky, AR Tedford, RJ Lahm, T Joynt, KE Kass, D Swenson, ER Goldstein, RH Leopold, JA Zamanian, RT Elwing, JM Baron, A Maddox, TM Choudhary, G AF Maron, B. A. Hess, E. Opotowsky, A. R. Tedford, R. J. Lahm, T. Joynt, K. E. Kass, D. Swenson, E. R. Goldstein, R. H. Leopold, J. A. Zamanian, R. T. Elwing, J. M. Baron, A. Maddox, T. M. Choudhary, G. CA Pulm Hypertension TI Subclinical Pulmonary Hypertension Is Associated With Mortality And Hospitalization In A Large Cohort Of Patients Referred For Cardiac Catheterization: Insights From The Va Cart Program SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Maron, B. A.; Joynt, K. E.] Boston VA Healthcare Syst, Boston, MA USA. [Hess, E.; Baron, A.; Maddox, T. M.] Vet Affairs Eastern Colorado Hlth Care Syst, Denver, CO USA. [Opotowsky, A. R.] Boston Childrens Hosp, Boston, MA USA. [Opotowsky, A. R.; Leopold, J. A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Tedford, R. J.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Lahm, T.] Richard L Roudebush VA Med Ctr, Indianapolis, IN USA. [Kass, D.] Univ Pittsburgh, Simmons Ctr Interstitial Lung Dis, Pittsburgh, PA USA. [Swenson, E. R.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Goldstein, R. H.] VA Boston Healthcare Syst, Boston, MA USA. [Leopold, J. A.] Harvard Univ, Sch Med, Boston, MA USA. [Zamanian, R. T.] Stanford Univ, Stanford, CA 94305 USA. [Elwing, J. M.] Univ Cincinnati, Cincinnati, OH USA. [Choudhary, G.] Providence VAMC, Providence, RI USA. EM bmaron@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A6451 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582807224 ER PT J AU Melzer, AC Au, DH AF Melzer, A. C. Au, D. H. TI Effectiveness Of Post-Discharge Smoking Cessation Management Following Exacerbation Of COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Au, D. H.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. EM acmelzer@u.washington.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A5387 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582807255 ER PT J AU Michaud, GC Hayes, MM McSparron, JI Channick, CL Thomson, C AF Michaud, G. C. Hayes, M. M. McSparron, J. I. Channick, C. L. Thomson, C. TI Improved Knowledge Following An Ats Multi-Day Skill-Based Endobronchial Ultrasound Course SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Michaud, G. C.] Yale Univ, New Haven, CT USA. [Hayes, M. M.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [McSparron, J. I.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [McSparron, J. I.] Harvard Univ, Sch Med, Boston, MA USA. [Channick, C. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Thomson, C.] Mt Auburn Hosp, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A5678 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582807539 ER PT J AU Miller, M Vasquez, J Weiner, M Chapman, A Engle, M Higgins, M Quinones, A Roselli, V Yoon, C Cattamanchi, A Davis, JL Stearman, R Phang, TL Kechris, K Fingerlin, T Datta, G Garcia, BJ Strong, M Geraci, MW Reves, RR Walter, ND AF Miller, M. Vasquez, J. Weiner, M. Chapman, A. Engle, M. Higgins, M. Quinones, A. Roselli, V. Yoon, C. Cattamanchi, A. Davis, J. L. Stearman, R. Phang, T. L. Kechris, K. Fingerlin, T. Datta, G. Garcia, B. J. Strong, M. Geraci, M. W. Reves, R. R. Walter, N. D. TI Evaluation Of African Blood Expression Signatures For Tuberculosis In Us Patients SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Miller, M.; Roselli, V.; Kechris, K.] Colorado Sch Publ Hlth, Aurora, CO USA. [Vasquez, J.; Yoon, C.; Cattamanchi, A.; Davis, J. L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Weiner, M.; Engle, M.] Vet Adm Med Ctr, San Antonio, TX USA. [Chapman, A.; Stearman, R.; Phang, T. L.; Geraci, M. W.; Walter, N. D.] Univ Colorado Denver, Aurora, CO USA. [Higgins, M.; Reves, R. R.] Denver Publ Hlth Dept, Denver, CO USA. [Quinones, A.] Denver Hlth, Denver, CO USA. [Fingerlin, T.; Datta, G.; Garcia, B. J.; Strong, M.] Natl Jewish Hlth, Denver, CO USA. EM mikaela.miller@ucdenver.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A5430 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582807291 ER PT J AU Montesi, S Pardo, A Selman, M Shea, BS Tager, AM Lagares, D AF Montesi, S. Pardo, A. Selman, M. Shea, B. S. Tager, A. M. Lagares, D. TI Soluble Ephrin-B2 Is A Novel Biomarker For Idiopathic Pulmonary Fibrosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Montesi, S.; Shea, B. S.; Lagares, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Montesi, S.; Pardo, A.] Univ Nacl Autonoma Mexico, Mexico City 04510, DF, Mexico. [Selman, M.] Inst Nacl Enfermedades Resp, Tlalpan, Mexico. [Tager, A. M.] Massachusetts Gen Hosp, Charlestown, MA USA. EM sbmontesi@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A4374 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582805433 ER PT J AU Morrow, J Qiu, W DeMeo, DL Houston, I Pinto-Plata, VM Celli, BR Marchetti, N Criner, GJ Bueno, R Washko, GR Glass, K Quackenbush, J Choi, AMK Silverman, EK Hersh, CP AF Morrow, J. Qiu, W. DeMeo, D. L. Houston, I. Pinto-Plata, V. M. Celli, B. R. Marchetti, N. Criner, G. J. Bueno, R. Washko, G. R. Glass, K. Quackenbush, J. Choi, A. M. K. Silverman, E. K. Hersh, C. P. TI Network Analysis Of Gene Expression In Severe Lung Tissue Samples SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Morrow, J.; Qiu, W.; DeMeo, D. L.; Houston, I.; Pinto-Plata, V. M.; Celli, B. R.; Bueno, R.; Washko, G. R.; Glass, K.; Silverman, E. K.; Hersh, C. P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Marchetti, N.; Criner, G. J.] Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. [Quackenbush, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Choi, A. M. K.] New York Presbyterian Hosp, Weill Cornell Med Coll, New York, NY USA. EM craig.hersh@channing.harvard.edu NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A1253 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582800252 ER PT J AU Mortensen, EM Alvarez, C Anzueto, A AF Mortensen, E. M. Alvarez, C. Anzueto, A. TI Safety Of Azithromycin In Older Patients With COPD Hospitalized With Pneumonia SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Mortensen, E. M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Alvarez, C.] Tech Univ Hlth Sci Ctr, Dallas, TX USA. [Anzueto, A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Anzueto, A.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A1775 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582801174 ER PT J AU Moschovis, PP Naidoo, N North, CM Brown, R Christiani, DC Hibberd, PL Chatterji, S AF Moschovis, P. P. Naidoo, N. North, C. M. Brown, R. Christiani, D. C. Hibberd, P. L. Chatterji, S. TI The Association Of Household Air Pollution And Smoking With Risk Of Obstructive Lung Disease Among Adults In India SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Moschovis, P. P.; North, C. M.; Brown, R.; Hibberd, P. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Naidoo, N.; Chatterji, S.] WHO, CH-1211 Geneva, Switzerland. [Christiani, D. C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A6353 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582802271 ER PT J AU Neville, TH Ahluwalia, S Smith, I Bando, J Yamamoto, M Prendergast, T Lorenz, K AF Neville, T. H. Ahluwalia, S. Smith, I. Bando, J. Yamamoto, M. Prendergast, T. Lorenz, K. TI Implementation And Use Of An Icu Family Meeting Template SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Neville, T. H.; Smith, I.; Bando, J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Ahluwalia, S.] RAND Corp, Santa Monica, CA USA. [Ahluwalia, S.] UCLA, Fielding Sch Publ Hlth, Santa Monica, CA USA. [Yamamoto, M.] Univ Calif Los Angeles, Los Angeles, CA USA. [Prendergast, T.] Portland VA Med Ctr, Portland, OR USA. [Prendergast, T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Lorenz, K.] VA Greater Los Angeles, Los Angeles, CA USA. [Lorenz, K.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A1086 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582800087 ER PT J AU North, CM Valeri, L Zhang, FY Lai, PS Su, L Hang, J Christiani, DC AF North, C. M. Valeri, L. Zhang, F. -Y. Lai, P. S. Su, L. Hang, J. Christiani, D. C. TI Cooking Fuel Type And Chronic Respiratory Symptoms In Shanghai, China: A Cross-Sectional Analysis Of An Urban, Retired Occupational Cohort SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [North, C. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Valeri, L.; Lai, P. S.; Christiani, D. C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Zhang, F. -Y.; Su, L.; Hang, J.] Shanghai Putuo Dist Peoples Hosp, Shanghai, Peoples R China. EM cnorth@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A4037 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582805096 ER PT J AU Novosad, S Choi, D Hedberg, K Henkle, E Schafer, S Siegel, SAR Slatore, CG Winthrop, KL AF Novosad, S. Choi, D. Hedberg, K. Henkle, E. Schafer, S. Siegel, S. A. R. Slatore, C. G. Winthrop, K. L. TI Predictors Of Death At Isolation Of Nontuberculous Mycobacteria In Respiratory Specimens SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Novosad, S.; Choi, D.; Siegel, S. A. R.; Winthrop, K. L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Hedberg, K.; Henkle, E.; Schafer, S.] Oregon Publ Hlth Div, Portland, OR USA. [Slatore, C. G.] Portland VA Med Ctr, Portland, OR USA. EM novosad@ohsu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582807082 ER PT J AU Oh, SS Wain, J Channick, CL AF Oh, S. S. Wain, J. Channick, C. L. TI Melanoptysis: An Unusual Complication Of Ebus-Tbna SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Oh, S. S.; Wain, J.; Channick, C. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. EM ssoh@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A3099 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582803374 ER PT J AU Parsons, EC Chaytor, NS Kapur, VK Caldwell, E Johnston, C Bell, K Vitiello, MV Hough, CL AF Parsons, E. C. Chaytor, N. S. Kapur, V. K. Caldwell, E. Johnston, C. Bell, K. Vitiello, M. V. Hough, C. L. TI Sleep Apnea Severity And Cognitive Function After Acute Respiratory Failure SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Parsons, E. C.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Parsons, E. C.; Chaytor, N. S.; Kapur, V. K.; Caldwell, E.; Johnston, C.; Bell, K.; Vitiello, M. V.] Univ Washington, Seattle, WA 98195 USA. [Hough, C. L.] Univ Washington, Harborview Med Ctr, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A4506 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582805565 ER PT J AU Patel, S Yoon, C Chaisson, LH Drain, P Cattamanchi, A AF Patel, S. Yoon, C. Chaisson, L. H. Drain, P. Cattamanchi, A. TI The Diagnostic Accuracy Of C-Reactive Protein For Active Tuberculosis: A Systematic Review And Meta-Analysis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Patel, S.; Yoon, C.; Chaisson, L. H.; Cattamanchi, A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Drain, P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM sweta.patel@ucsf.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A3305 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582803579 ER PT J AU Paul, TK Oh, SS Bando, JM Lee, JM Susanto, I AF Paul, T. K. Oh, S. S. Bando, J. M. Lee, J. M. Susanto, I. TI Central Airway Obstruction From Endobronchial Mucormycosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Paul, T. K.; Bando, J. M.; Lee, J. M.; Susanto, I.] Univ Calif Los Angeles, Los Angeles, CA USA. [Paul, T. K.; Oh, S. S.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Paul, T. K.; Oh, S. S.] West Los Angeles VA Med Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A1856 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582801255 ER PT J AU Paula, LSDC Spieth, PM Guldner, A De Abreu, MG Carvalho, AR Melo, MFV AF Paula, L. S. D. C. Spieth, P. M. Guldner, A. De Abreu, M. G. Carvalho, A. R. Vidal Melo, M. F. TI Comparison Between Strain Measures And A Volume Dependent Elastance Model In Health Lungs SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Paula, L. S. D. C.; Vidal Melo, M. F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Spieth, P. M.; De Abreu, M. G.] Univ Hosp Dresden, Dresden, Germany. [Guldner, A.] Univ Hosp Carl Gustav Carus, Dresden, Germany. [Carvalho, A. R.] Univ Fed Rio de Janeiro, Inst Biophys Carlos Chagas Filho, Rio De Janeiro, Brazil. EM LSANTOSDACRUZPAULA@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A3646 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582804296 ER PT J AU Pavel, AB Campbell, J Luo, L Liu, G Xiao, J Guardela, BJ Tedrow, J Aleksyev, Y Yang, IV Correll, M Geraci, MW Quackenbush, J Sciurba, FC Schwartz, DA Kaminski, N Beane, J Spira, A Lenburg, ME AF Pavel, A. B. Campbell, J. Luo, L. Liu, G. Xiao, J. Guardela, B. J. Tedrow, J. Aleksyev, Y. Yang, I. V. Correll, M. Geraci, M. W. Quackenbush, J. Sciurba, F. C. Schwartz, D. A. Kaminski, N. Beane, J. Spira, A. Lenburg, M. E. TI Differential Connectivity Of Microrna/mrna Association Networks Reveals Bronchial Micrornas Associated With Chronic Obstructive Pulmonary Disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Pavel, A. B.; Campbell, J.; Luo, L.; Liu, G.; Xiao, J.; Aleksyev, Y.; Beane, J.; Spira, A.; Lenburg, M. E.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Guardela, B. J.; Tedrow, J.; Sciurba, F. C.] Univ Pittsburgh, Simmons Ctr Interstitial Lung Dis, Pittsburgh, PA USA. [Tedrow, J.; Yang, I. V.] Univ Colorado, Aurora, CO USA. [Correll, M.; Quackenbush, J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Geraci, M. W.; Schwartz, D. A.] Univ Colorado, Aurora, CO USA. [Kaminski, N.] Univ Pittsburgh, Pittsburgh, PA USA. EM anapavel@bu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A2932 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582803176 ER PT J AU Rial, SP Robles-Mateo, SA Venegas, JG Gonzalez-Mangado, N Peces-Barba, G AF Perez Rial, S. Robles-Mateo, S. A. Venegas, J. G. Gonzalez-Mangado, N. Peces-Barba, G. TI Evaluation Of Lung Damage Induced By Electronic Cigarette In Mice SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Perez Rial, S.; Robles-Mateo, S. A.; Gonzalez-Mangado, N.; Peces-Barba, G.] IIS Fdn Jimenez Diaz CIBERES, Madrid, Spain. [Venegas, J. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM sperezr@fjd.es NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A6474 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582808552 ER PT J AU Prieto-Centurion, V Zaidi, F Coultas, DB Casaburi, R Rand, CS Krishnan, JA AF Prieto-Centurion, V. Zaidi, F. Coultas, D. B. Casaburi, R. Rand, C. S. Krishnan, J. A. TI Comparison Of Commercially-Available Pedometers For Potential Use For Promotion Of Lifestyle Physical Activity SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Prieto-Centurion, V.; Zaidi, F.; Krishnan, J. A.] Univ Illinois, Chicago, IL USA. [Coultas, D. B.] Portland VA Med Ctr, Portland, OR USA. [Coultas, D. B.; Casaburi, R.] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Rand, C. S.] Johns Hopkins Univ, Baltimore, MD USA. EM vprieto@uic.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A5204 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582807024 ER PT J AU Prieto-Centurion, V Zaidi, F Bracken, NE Norwick, L Coultas, DB Casaburi, R Rand, CS Jaffe, HA Krishnan, JA AF Prieto-Centurion, V. Zaidi, F. Bracken, N. E. Norwick, L. Coultas, D. B. Casaburi, R. Rand, C. S. Jaffe, H. A. Krishnan, J. A. TI Patient Perspectives And Barriers To Pulmonary Rehabilitation Following Hospitalizations For Chronic Obstructive Pulmonary Disease Exacerbations SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Prieto-Centurion, V.; Zaidi, F.; Bracken, N. E.; Norwick, L.; Jaffe, H. A.; Krishnan, J. A.] Univ Illinois, Chicago, IL USA. [Coultas, D. B.] Portland VA Med Ctr, Portland, OR USA. [Casaburi, R.] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Rand, C. S.] Johns Hopkins Univ, Baltimore, MD USA. EM vprieto@uic.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A2222 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582802017 ER PT J AU Radicioni, G Ford, A Boucher, RC Luster, A Harris, RS Medoff, BD Kesimer, M AF Radicioni, G. Ford, A. Boucher, R. C. Luster, A. Harris, R. S. Medoff, B. D. Kesimer, M. TI Mucus/mucin Composition In Response To Antigen Challenge In Asthmatic And Allergic Non-Asthmatic Subjects SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Radicioni, G.; Ford, A.; Boucher, R. C.; Kesimer, M.] Univ N Carolina, Chapel Hill, NC USA. [Luster, A.; Harris, R. S.; Medoff, B. D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Luster, A.; Harris, R. S.] Harvard Univ, Sch Med, Boston, MA USA. EM kesimer@med.unc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A2734 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582802585 ER PT J AU Reinke, LF Feemster, LC Mc Dowell, J Gunnink, E Tartaglione, EV Udris, EM Au, DH AF Reinke, L. F. Feemster, L. C. Mc Dowell, J. Gunnink, E. Tartaglione, E. V. Udris, E. M. Au, D. H. TI Long Term Impact Of An End-Of-Life Communication Intervention Among Veterans With COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Reinke, L. F.; Mc Dowell, J.; Gunnink, E.; Tartaglione, E. V.; Udris, E. M.] VA Puget Sound, Edmonds, WA USA. [Feemster, L. C.] Univ Washington, VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98195 USA. [Au, D. H.] Univ Washington, Seattle, WA 98195 USA. EM reinkl@u.washington.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A3916 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582804583 ER PT J AU Rinne, S Wong, E Hebert, P Au, DH Concato, J Liu, CF AF Rinne, S. Wong, E. Hebert, P. Au, D. H. Concato, J. Liu, C. -F. TI Average Facility Length Of Stay For COPD Hospitalizations Is Not Associated With Readmission Or Mortality SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Rinne, S.] Yale, New Haven, CT USA. [Wong, E.; Hebert, P.; Liu, C. -F.] VA Puget Sound, Seattle, WA USA. [Au, D. H.] Dept Vet Affairs VA Puget Sound Healthcare Syst, Seattle, WA USA. [Concato, J.] Yale Univ, Sch Med, Vet Affairs Med Ctr, West Haven, CT 06516 USA. EM seppo.rinne@yale.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A6171 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582808406 ER PT J AU Rinne, S Wong, E Hebert, P Au, DH Justice, AC Liu, CF AF Rinne, S. Wong, E. Hebert, P. Au, D. H. Justice, A. C. Liu, C. -F. TI Organizational Factors And Risk Of Readmission Among Patients Hospitalized For COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Rinne, S.] Yale Univ, New Haven, CT USA. [Wong, E.; Hebert, P.; Liu, C. -F.] VA Puget Sound, Seattle, WA USA. [Au, D. H.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Justice, A. C.] Yale Univ, West Haven, CT USA. EM seppo.rinne@yale.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A3888 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582804555 ER PT J AU Sauler, M McGinnis, KM Berical, A Crothers, KA Akgun, KM Huang, L Goetz, MB Rimland, D Bucala, R Lee, PJ AF Sauler, M. McGinnis, K. M. Berical, A. Crothers, K. A. Akgun, K. M. Huang, L. Goetz, M. B. Rimland, D. Bucala, R. Lee, P. J. TI Differential Association Of Macrophage Migration Inhibitory Factor (mif) Promoter Polymorphisms With Chronic Obstructive Pulmonary Disease (COPD) By Hiv Status And Race SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Sauler, M.; Berical, A.; Akgun, K. M.; Bucala, R.; Lee, P. J.] Yale Univ, Sch Med, New Haven, CT USA. [McGinnis, K. M.] Univ Pittsburgh, Pittsburgh, PA USA. [Crothers, K. A.] Univ Washington, Sch Med, Seattle, WA USA. [Huang, L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Huang, L.] San Francisco Gen Hosp, San Francisco, CA 94110 USA. [Goetz, M. B.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Rimland, D.] Emory Univ, Decatur, GA USA. EM maor.sauler@yale.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A1055 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582800056 ER PT J AU Sigel, KM Wisnivesky, JP Kong, C Braithwaite, RS Park, LS Dubrow, R Gibert, C Brown, ST Rimland, D Rodriguez-Barradas, MC Goetz, MB Bedimo, R Crothers, KA AF Sigel, K. M. Wisnivesky, J. P. Kong, C. Braithwaite, R. S. Park, L. S. Dubrow, R. Gibert, C. Brown, S. T. Rimland, D. Rodriguez-Barradas, M. C. Goetz, M. B. Bedimo, R. Crothers, K. A. TI Frequency Of Complications After Lung Biopsy In Hiv-Infected Compared To Hiv-Uninfected Patients: Implications For Lung Cancer Screening SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Sigel, K. M.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Wisnivesky, J. P.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Kong, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kong, C.] Harvard Univ, Sch Med, Boston, MA USA. [Braithwaite, R. S.] NYU, Sch Med, New York, NY USA. [Park, L. S.; Dubrow, R.] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Gibert, C.] Vet Affairs Med Ctr, Washington, DC 20422 USA. [Brown, S. T.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Rimland, D.] Vet Affairs Med Ctr, Atlanta, GA 30033 USA. [Rimland, D.] Emory Univ, Atlanta, GA 30322 USA. [Rodriguez-Barradas, M. C.] Vet Affairs Med Ctr, Houston, TX 77030 USA. [Rodriguez-Barradas, M. C.] Baylor Sch Med, Houston, TX USA. [Goetz, M. B.] Univ Calif Los Angeles, Vet Affairs Med Ctr, Los Angeles, CA USA. [Goetz, M. B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Bedimo, R.] Vet Affairs Med Ctr, Dallas, TX USA. [Crothers, K. A.] Univ Washington, Sch Med, Seattle, WA USA. EM crothk@uw.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A3586 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582804236 ER PT J AU Solomon, GM Francis, R Chu, K Gabriel, G Birket, S Trombley, J Mojahed, D Lemke, K Klena, N Tearney, G Lo, C Rowe, SM AF Solomon, G. M. Francis, R. Chu, K. Gabriel, G. Birket, S. Trombley, J. Mojahed, D. Lemke, K. Klena, N. Tearney, G. Lo, C. Rowe, S. M. TI mu oct To Interrogate Mechanisms Of Altered Ciliary Dynamics And Mucus Transport SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Solomon, G. M.; Birket, S.; Trombley, J.; Rowe, S. M.] Univ Alabama Birmingham, Birmingham, AL USA. [Francis, R.; Gabriel, G.; Lemke, K.; Klena, N.; Lo, C.] Univ Pittsburgh, Pittsburgh, PA USA. [Chu, K.; Mojahed, D.; Tearney, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM msolomon@uab.edu NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A3927 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582804594 ER PT J AU Stanford, RH Lin, X Nag, A Camargo, CA D'Agostino, R Fuhlbrigge, A Han, MK Munson, JC AF Stanford, R. H. Lin, X. Nag, A. Camargo, C. A. D'Agostino, R. Fuhlbrigge, A. Han, M. K. Munson, J. C. CA READ-COPD TI Recursive Partitioning Analysis Of Risk Factors For 30-Day All-Cause Readmission Following A COPD Hospitalization: Data From The Read-COPD Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Stanford, R. H.; Lin, X.; Nag, A.] GlaxoSmithKline, Res Triangle Pk, NC USA. [Camargo, C. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [D'Agostino, R.] Boston Univ, Boston, MA 02215 USA. [Fuhlbrigge, A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Han, M. K.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Munson, J. C.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A1105 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582800106 ER PT J AU Stinson, D Marchetti, N Hart, JE Blanc, PD Washko, G Jaramillo, M James, J Garshick, E AF Stinson, D. Marchetti, N. Hart, J. E. Blanc, P. D. Washko, G. Jaramillo, M. James, J. Garshick, E. TI Risk Of Chronic Respiratory Symptoms, Qct Measures Of Disease, And COPD Attributable To Occupational Factors Is Similar For Job Exposure Matrix, Self-Reported Exposure, And Lower Educational Level As An Exposure Surrogate In COPDgene SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Stinson, D.; Jaramillo, M.; James, J.] Natl Jewish Hlth, Denver, CO USA. [Stinson, D.] Temple Univ, Sch Med, Philadelphia, PA 19122 USA. [Marchetti, N.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Hart, J. E.; Washko, G.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Garshick, E.] VA Boston Healthcare Syst, Boston, MA USA. [Garshick, E.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Garshick, E.] Harvard Univ, Sch Med, Boston, MA USA. EM dsstinso@hotmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A2592 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582802446 ER PT J AU Suter, MJ Adams, DC Hariri, LP Miller, AJ Wang, Y Luster, AD Bouma, BE Medoff, BD AF Suter, M. J. Adams, D. C. Hariri, L. P. Miller, A. J. Wang, Y. Luster, A. D. Bouma, B. E. Medoff, B. D. TI Non-Invasive Assessment Of Airway Smooth Muscle Mass, Distribution And Contractile Force Using Birefringence Microscopy SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Suter, M. J.; Adams, D. C.; Hariri, L. P.; Miller, A. J.; Wang, Y.; Luster, A. D.; Bouma, B. E.; Medoff, B. D.] Harvard Univ, Sch Med, Boston, MA USA. [Suter, M. J.; Adams, D. C.; Hariri, L. P.; Miller, A. J.; Wang, Y.; Luster, A. D.; Bouma, B. E.; Medoff, B. D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM msuter@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A2465 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582802319 ER PT J AU Szabari, MV Takahashi, K Carter, EA Feng, Y Chao, W Musch, G AF Szabari, M. V. Takahashi, K. Carter, E. A. Feng, Y. Chao, W. Musch, G. TI Inflammatory Effect Of Protective Long-Term Mechanical Ventilation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Szabari, M. V.; Takahashi, K.; Carter, E. A.; Feng, Y.; Chao, W.; Musch, G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. EM szabari.margit@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A3121 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582803396 ER PT J AU Tapson, V Joish, VN Platt, D Xia, F Teal, S Abad, M Satler, C Channick, RN AF Tapson, V. Joish, V. N. Platt, D. Xia, F. Teal, S. Abad, M. Satler, C. Channick, R. N. TI Evaluating Routine Disease Monitoring Practice In Incident Pulmonary Embolism Patients In The United States SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Tapson, V.] Cedars Sinai Med Ctr, Beverly Hills, CA USA. [Tapson, V.; Joish, V. N.; Platt, D.; Xia, F.; Satler, C.] Bayer HealthCare Pharmaceut, Whippany, NJ USA. [Teal, S.; Abad, M.] Bayer Pharma AG, Berlin, Germany. [Channick, R. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A4881 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582806315 ER PT J AU Teerapuncharoen, K Wells, JM Dransfield, MT Rowe, SM AF Teerapuncharoen, K. Wells, J. M. Dransfield, M. T. Rowe, S. M. TI Acquired Cftr Dysfunction And Pulmonary Arterial Enlargement In Chronic Obstructive Pulmonary Disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Teerapuncharoen, K.; Wells, J. M.; Rowe, S. M.] Univ Alabama Birmingham, Birmingham, AL USA. [Teerapuncharoen, K.; Dransfield, M. T.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A3830 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582804472 ER PT J AU Tejera, P Laucho-Contreras, ME Owen, CA Christiani, DC AF Tejera, P. Laucho-Contreras, M. E. Owen, C. A. Christiani, D. C. TI Adenoviral Augmentation Of Rs2664581-Mutant And Wild Type Pre-Elafin In A Murine Model Of P. AerugINOSa Pneumonia Induced-Ali SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Tejera, P.] HSPH, Boston, MA USA. [Laucho-Contreras, M. E.; Owen, C. A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Christiani, D. C.] Harvard Univ, Sch Publ Hlth, Sch Med, Boston, MA 02115 USA. [Christiani, D. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ptejera@hsph.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A2381 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582802175 ER PT J AU Tennis, M Nield, L Merrick, D Keith, RL AF Tennis, M. Nield, L. Merrick, D. Keith, R. L. TI Personalized Lung Cancer Chemoprevention Using Ppar gamma And Its Downstream Targets SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Tennis, M.; Merrick, D.] Univ Colorado Denver, Aurora, CO USA. [Nield, L.] Univ Colorado, Aurora, CO USA. [Keith, R. L.] Univ Colorado, Denver Vet Affairs Med Ctr, Denver, CO 80202 USA. EM meredith.tennis@ucdenver.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A2431 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582802225 ER PT J AU Venegas, JG Greenblatt, EE Kelly, VJ Winkler, T Kone, M Katz, I Martin, AR Caillibotte, G Harris, RS AF Venegas, J. G. Greenblatt, E. E. Kelly, V. J. Winkler, T. Kone, M. Katz, I. Martin, A. R. Caillibotte, G. Harris, R. S. TI Effects Of Carrier Gas On Regional Aerosol Deposition In The Lung SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Venegas, J. G.; Greenblatt, E. E.; Kelly, V. J.; Winkler, T.; Kone, M.; Harris, R. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Venegas, J. G.; Winkler, T.; Harris, R. S.] Harvard Univ, Sch Med, Boston, MA USA. [Greenblatt, E. E.] MIT, Boston, MA USA. [Katz, I.; Caillibotte, G.] Air Liquide, Les Loges En Josas, France. [Martin, A. R.] Univ Alberta, Edmonton, AB, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A3929 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582804596 ER PT J AU Wiener, RS Koppelman, E Slatore, CG Clark, JA AF Wiener, R. S. Koppelman, E. Slatore, C. G. Clark, J. A. TI Patients' Impressions Of Communication With Their Clinicians Surrounding Low-Dose CT Lung Cancer Screening: A Qualitative Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Wiener, R. S.; Koppelman, E.; Clark, J. A.] Edith Nourse Rogers Mem VA Hosp, Bedford, MA USA. [Slatore, C. G.] Portland VA Med Ctr, Portland, OR USA. EM rwiener@bu.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A6120 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582808355 ER PT J AU Wilson, JG Liu, K Zhuo, H Caballero, L McMillan, M Fang, X Cosgrove, K Vojnik, R Calfee, CS Lee, JW Rogers, AJ Levitt, JE Wiener-Kronish, JP Bajwa, E Leavitt, A McKenna, D Thompson, T Matthay, MA AF Wilson, J. G. Liu, K. Zhuo, H. Caballero, L. McMillan, M. Fang, X. Cosgrove, K. Vojnik, R. Calfee, C. S. Lee, J. -W. Rogers, A. J. Levitt, J. E. Wiener-Kronish, J. P. Bajwa, E. Leavitt, A. McKenna, D. Thompson, T. Matthay, M. A. TI Mesenchymal Stem (stromal) Cells For Treatment Of Ards:A Phase 1 Clinical Trial SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Wilson, J. G.; Liu, K.; Zhuo, H.; Caballero, L.; McMillan, M.; Fang, X.; Calfee, C. S.; Lee, J. -W.; Leavitt, A.; Matthay, M. A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Cosgrove, K.; Wiener-Kronish, J. P.; Bajwa, E.; Thompson, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Vojnik, R.; Rogers, A. J.; Levitt, J. E.] Stanford Univ, Stanford, CA 94305 USA. [McKenna, D.] Univ Minnesota, Cellular Therapy, St Paul, MN 55108 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582806554 ER PT J AU Wilson, ME Hinds, RF Zubek, L Gajic, O Talmor, DS Banner-Goodspeed, VM Muller, A Rickett, DM Benoit, DD AF Wilson, M. E. Hinds, R. F. Zubek, L. Gajic, O. Talmor, D. S. Banner-Goodspeed, V. M. Muller, A. Rickett, D. M. Benoit, D. D. TI Perceptions Of Appropriateness Of Medical Treatment Among Patients And Families In Us And Hungarian Intensive Care Units SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Wilson, M. E.; Hinds, R. F.; Gajic, O.] Mayo Clin, Rochester, MN USA. [Wilson, M. E.; Zubek, L.] Semmelweis Univ, Dept Anaesthesia & Intens Therapy, H-1085 Budapest, Hungary. [Talmor, D. S.; Banner-Goodspeed, V. M.; Muller, A.] Beth Israel Deaconness Med Ctr, Boston, MA USA. [Rickett, D. M.] Henry Mayo Newhall Mem Hosp, Valencia, CA USA. [Benoit, D. D.] Ghent Univ Hosp, Dept Intens Care Med, Ghent, Belgium. EM Wilson.Michael1@mayo.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A3778 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582804420 ER PT J AU Winkler, T Venegas, JG Harris, RS AF Winkler, T. Venegas, J. G. Harris, R. S. TI Airway Transmural Pressure During Bronchoconstriction SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Winkler, T.; Venegas, J. G.; Harris, R. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Winkler, T.; Venegas, J. G.; Harris, R. S.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A1205 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582800204 ER PT J AU Witkin, AS Rodriguez-Lopez, J Jaff, M Kabrhel, C Rosenfield, K Channick, RN AF Witkin, A. S. Rodriguez-Lopez, J. Jaff, M. Kabrhel, C. Rosenfield, K. Channick, R. N. TI Major Pulmonary Embolism After Non-Major Knee Surgery SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Witkin, A. S.; Rodriguez-Lopez, J.; Jaff, M.; Kabrhel, C.; Rosenfield, K.; Channick, R. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM aswitkin@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582806316 ER PT J AU Yonker, LM Raby, BA Toledo, DM Hoffman, E Kinane, TB AF Yonker, L. M. Raby, B. A. Toledo, D. M. Hoffman, E. Kinane, T. B. TI Clinical Pulmonary Genetics: A Multidisciplinary Approach To Pediatric Patients With Rare Lung Disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Yonker, L. M.; Kinane, T. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Raby, B. A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Toledo, D. M.; Hoffman, E.] Partners Ctr Personalized Genet Med, Cambridge, MA USA. EM lyonker@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A5913 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582808163 ER PT J AU Yonker, LM Mou, H Chu, KK Pazos, MA Eaton, AD Tearney, G Rajagopal, J Hurley, BP AF Yonker, L. M. Mou, H. Chu, K. K. Pazos, M. A. Eaton, A. D. Tearney, G. Rajagopal, J. Hurley, B. P. TI A Novel Model: Transepithelial Neutrophil Migration Using Differentiated Human Airway Stem Cell Air-Liquid Interface SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Yonker, L. M.; Pazos, M. A.; Eaton, A. D.; Hurley, B. P.] Massachusetts Gen Hosp, Charlestown, MA USA. [Mou, H.; Tearney, G.; Rajagopal, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tearney, G.] Harvard Univ, Sch Med, Boston, MA USA. EM lyonker@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A4342 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582805401 ER PT J AU Yu, B Muenster, S Blaesi, A Bloch, DB Zapol, WM AF Yu, B. Muenster, S. Blaesi, A. Bloch, D. B. Zapol, W. M. TI Producing Nitric Oxide By Pulsed Electrical Discharge In Air For Inhalation Therapy SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Yu, B.; Muenster, S.; Blaesi, A.; Bloch, D. B.; Zapol, W. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM byu1@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A1960 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582801359 ER PT J AU Zazzeron, L Nakagawa, A Liu, C Franco, W Farinelli, WA Anderson, RR Zapol, WM AF Zazzeron, L. Nakagawa, A. Liu, C. Franco, W. Farinelli, W. A. Anderson, R. R. Zapol, W. M. TI Pulmonary Phototherapy: Preventing And Treating Carbon Monoxide Poisoning SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Zazzeron, L.; Nakagawa, A.; Liu, C.; Franco, W.; Farinelli, W. A.; Anderson, R. R.; Zapol, W. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zazzeron, L.; Nakagawa, A.; Liu, C.; Franco, W.; Farinelli, W. A.; Anderson, R. R.; Zapol, W. M.] Harvard Univ, Sch Med, Boston, MA USA. EM lzazzeron@partners.org NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A6449 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582807222 ER PT J AU Zider, A Pezeshkpour, G Betancourt, J AF Zider, A. Pezeshkpour, G. Betancourt, J. TI Combined Lung Neuroendocrine/adenocarcinoma With Pulmonary Tumor Thrombotic Microangiopathy: A Rare Cause Of Severe Hypoxemia And Pulmonary Hypertension SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT International Conference of the American-Thoracic-Society (ATS) CY MAY 15-20, 2015 CL Denver, CO SP Amer Thorac Soc C1 [Zider, A.] Univ Calif Los Angeles, Los Angeles, CA USA. [Pezeshkpour, G.; Betancourt, J.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Pezeshkpour, G.; Betancourt, J.] West Los Angeles VA Med Ctr, Los Angeles, CA USA. EM jaimebetancourt@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2015 VL 191 MA A5868 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DO2AW UT WOS:000377582808119 ER PT J AU Vaughn-Cooke, M Nembhard, HB Ulbrecht, J Gabbay, R AF Vaughn-Cooke, Monifa Nembhard, Harriet Black Ulbrecht, Jan Gabbay, Robert TI Informing Patient Self-Management Technology Design Using a Patient Adherence Error Classification SO ENGINEERING MANAGEMENT JOURNAL LA English DT Article DE Human Error; Diabetes; Patient Self-Management; Design Decision Making; Human Factors Engineering; Risk Management ID SYSTEMS; CARE AB Patient non-adherence with self-management increases patient health risks and financial burdens on the healthcare system. Human error classifications can potentially elucidate and quantify the behavioral manifestations of patient non-adherence and inform design decision making. We present the results of a study of the error classification approach focusing on self-monitoring of blood glucose (SMBG) adherence in diabetes patients. In these patients, the significant error types are: (1) skill-based errors and (2) intentional violations. We also discuss risk mitigation strategies for SMBG patient adherence and the use of an error classification approach to inform formative device evaluations. C1 [Vaughn-Cooke, Monifa] Univ Maryland, Mech Engn, College Pk, MD 20742 USA. [Vaughn-Cooke, Monifa] Univ Maryland, Reliabil Engn Grad Program, College Pk, MD 20742 USA. [Nembhard, Harriet Black] Penn State Univ, Ind Engn, University Pk, PA 16802 USA. [Nembhard, Harriet Black] Penn State Univ, Ctr Integrated Healthcare Delivery Syst, University Pk, PA 16802 USA. [Ulbrecht, Jan] Penn State Univ, Biobehav Hlth & Med, University Pk, PA 16802 USA. [Gabbay, Robert] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Vaughn-Cooke, M (reprint author), Univ Maryland, Dept Mech Engn, 0151E Glenn L Martin Hall, College Pk, MD 20742 USA. EM mvc@umd.edu NR 24 TC 1 Z9 1 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1042-9247 EI 2377-0643 J9 ENG MANAG J JI EMJ-Eng. Manag. J. PY 2015 VL 27 IS 3 SI SI BP 124 EP 130 DI 10.1080/10429247.2015.1061889 PG 7 WC Engineering, Industrial; Management SC Engineering; Business & Economics GA DO1MJ UT WOS:000377542100004 ER PT J AU Dunn, EC Miliren, CE Evans, CR Subramanian, S Richmond, TK AF Dunn, E. C. Miliren, C. E. Evans, C. R. Subramanian, S. Richmond, T. K. TI Using cross-Classified Multilevel Models to Disentangle the Relative Influence of Schools and Neighborhoods on Adolescents' Depressive Symptoms. SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th IEA World Congress of Epidemiology (WCE) CY AUG 17-21, 2014 CL Anchorage, AK SP Int Epidemiol Assoc C1 [Dunn, E. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Miliren, C. E.] Childrens Hosp, Boston, MA 02115 USA. [Evans, C. R.; Subramanian, S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Richmond, T. K.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 EI 1464-3685 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PY 2015 VL 44 SU 1 MA 2718 BP 49 EP 49 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DM9BV UT WOS:000376659900109 ER PT J AU Gilthorpe, MS Dahly, DL Tu, YK Kubzansky, LD Goodman, E AF Gilthorpe, M. S. Dahly, D. L. Tu, Y. K. Kubzansky, L. D. Goodman, E. TI Growth Mixture Models in Epidemiology and the Impact of an Incorrectly Specified Random Structure on Model Inferences. SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th IEA World Congress of Epidemiology (WCE) CY AUG 17-21, 2014 CL Anchorage, AK SP Int Epidemiol Assoc C1 [Gilthorpe, M. S.] Univ Leeds, Leeds, W Yorkshire, England. [Dahly, D. L.] Natl Univ Ireland Univ Coll Cork, Cork, Ireland. [Tu, Y. K.] Natl Taiwan Univ, Taipei 10764, Taiwan. [Kubzansky, L. D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Goodman, E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 EI 1464-3685 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PY 2015 VL 44 SU 1 MA 3569 BP 51 EP 51 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DM9BV UT WOS:000376659900113 ER PT J AU Dunn, EC Wiste, A Radmanesh, F Koenen, KC Purcell, S Cornelis, M Rosand, J Kraft, P Wassertheil-Smoller, S Smoller, J AF Dunn, E. C. Wiste, A. Radmanesh, F. Koenen, K. C. Purcell, S. Cornelis, M. Rosand, J. Kraft, P. Wassertheil-Smoller, S. Smoller, J. TI Genome-Wide Association Study (GWAS) and Genome-Environment Wide Interaction Study (GEWIS) of Late-Life Depressive Symptoms in Women. SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th IEA World Congress of Epidemiology (WCE) CY AUG 17-21, 2014 CL Anchorage, AK SP Int Epidemiol Assoc C1 [Dunn, E. C.; Wiste, A.; Radmanesh, F.; Purcell, S.; Rosand, J.; Smoller, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Koenen, K. C.] Columbia Univ, New York, NY USA. [Cornelis, M.; Kraft, P.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Wassertheil-Smoller, S.] Albert Einstein Coll Med, Bronx, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 EI 1464-3685 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PY 2015 VL 44 SU 1 MA 2719 BP 181 EP 182 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DM9BV UT WOS:000376659900462 ER PT J AU Faustman, DL Davis, M AF Faustman, Denise L. Davis, Miriam BE Nunes, KP TI The Pancreas Secreting Insulin for Decades after Onset of Type I Diabetes - Implications for Care and Management SO MAJOR TOPICS IN TYPE 1 DIABETES LA English DT Article; Book Chapter DE Type 1 diabetes; C-peptide; insulin secretion; complications ID BETA-CELL FUNCTION; C-PEPTIDE; COMPLICATIONS TRIAL; DIAGNOSIS; MELLITUS; AGE; PREVALENCE; DURATION; CHILDREN; DECLINE AB Up until recently, the prevailing dogma was that insulin secretion ceased within a couple of years after the diagnosis of type I diabetes, a clinical time period called the honeymoon. But a series of recent studies have established that release of C-peptide, which is the best measure of endogenous insulin production, can commonly persist for decades after disease onset. The release of C-peptide, even at low levels, is shown to have functional and clinical significance. For example, C-peptide levels >10 pmol/l are associated with fewer diabetes complications, i.e., nephropathy, neuropathy, foot ulcers, and retinopathy. The diabetic population may also be heterogeneous in risk for fall in C-peptide, with early age of diabetes onset a risk factor for more rapid C-peptide decline. The persistence of insulin release for decades and its functional and clinical significance suggest that assays for C-peptide should be a regular part of diabetes management. Furthermore, patients with established diabetes should be eligible to participate in clinical trials of immune therapies since preservation of these low levels appears clinically important to prevent complications. C1 [Faustman, Denise L.; Davis, Miriam] Massachusetts Gen Hosp, Immunobiol Lab, Boston, MA 02114 USA. [Faustman, Denise L.] Harvard Univ, Sch Med, Boston, MA USA. RP Faustman, DL (reprint author), Massachusetts Gen Hosp, Immunobiol Lab, Boston, MA 02114 USA. EM faustman@helix.mgh.harvard.edu NR 30 TC 0 Z9 0 U1 0 U2 0 PU INTECH EUROPE PI RIJEKA PA JANEZA TRDINE9, RIJEKA, 51000, CROATIA BN 978-953-51-2204-3 PY 2015 BP 21 EP 29 DI 10.5772/61234 D2 10.5772/59335 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BE6JK UT WOS:000374244900003 ER PT S AU Evins, AE Cather, C AF Evins, A. Eden Cather, Corinne BE DeBiasi, M TI Effective Cessation Strategies for Smokers with Schizophrenia SO NICOTINE USE IN MENTAL ILLNESS AND NEUROLOGICAL DISORDERS SE International Review of Neurobiology LA English DT Review; Book Chapter ID PLACEBO-CONTROLLED TRIAL; NICOTINIC RECEPTOR MECHANISMS; BUPROPION SUSTAINED-RELEASE; SERIOUS MENTAL-ILLNESS; SMOKING-CESSATION; CIGARETTE-SMOKING; BIPOLAR DISORDER; DOUBLE-BLIND; UNITED-STATES; SCHIZOAFFECTIVE DISORDER AB Despite availability of smoking cessation aids with proven efficacy and tolerability in those with schizophrenia, addiction to tobacco-derived nicotine remains highly prevalent among those with schizophrenia spectrum disorders. While smokers with serious mental illness have been excluded from most large nicotine-dependence treatment studies, and these treatments are woefully underutilized for smokers with psychiatric illness, a growing evidence base is available to guide cessation treatment for smokers with schizophrenia. The aim of this review is to present the evidence on safety and efficacy of smoking cessation interventions for those with schizophrenia spectrum illness. Smokers with schizophrenia spectrum disorders should receive varenicline or bupropion with or without nicotine replacement therapy in combination with behavioral treatment. Clinical practice guidelines now recommend duration of treatment be 12 weeks, but evidence indicates that maintenance pharmacotherapy for 1 year improves sustained abstinence rates. Controlled trials have found no evidence that in patients with serious mental illness, the use of pharmacotherapeutic cessation aids worsens psychiatric symptoms or increases the rate of psychiatric adverse events. Converging evidence indicates that a majority of smokers with serious mental illness want to quit smoking and that available pharmacotherapeutic cessation aids combined with behavioral support are both effective for, and well tolerated by, these smokers. C1 [Evins, A. Eden; Cather, Corinne] Massachusetts Gen Hosp, Ctr Addict Med, Boston, MA 02114 USA. [Evins, A. Eden; Cather, Corinne] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Evins, AE (reprint author), Massachusetts Gen Hosp, Ctr Addict Med, Boston, MA 02114 USA. EM a_eden_evins@hms.harvard.edu NR 80 TC 4 Z9 4 U1 7 U2 9 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 BN 978-0-12-801626-8; 978-0-12-801583-4 J9 INT REV NEUROBIOL JI Int. Rev. Neurobiol. PY 2015 VL 124 BP 133 EP 147 DI 10.1016/bs.irn.2015.08.001 PG 15 WC Neurosciences SC Neurosciences & Neurology GA BE8BF UT WOS:000376192100006 PM 26472528 ER PT B AU Leonard, DA Kurtz, JM Cetrulo, CL AF Leonard, David A. Kurtz, Josef M. Cetrulo, Curtis L. BE Brandacher, G TI Mixed Chimerism for Tolerance Induction of Vascularized Composite Allografts SO SCIENCE OF RECONSTRUCTIVE TRANSPLANTATION SE Stem Cell Biology and Regenerative Medicine LA English DT Article; Book Chapter ID REGULATORY T-CELLS; BONE-MARROW-TRANSPLANTATION; LARGE-ANIMAL-MODEL; VERSUS-HOST-DISEASE; MISMATCHED RENAL-TRANSPLANTATION; CLINICAL HAND TRANSPLANTATION; HUMAN FACE TRANSPLANTATION; TISSUE LIMB ALLOGRAFTS; NATURAL-KILLER-CELLS; IN-VIVO C1 [Cetrulo, Curtis L.] Harvard Univ, Sch Med, Vascularized Composite Allotransplantat Lab, Transplantat Biol Res Ctr,Massachusetts Gen Hospi, 15 Parkman St, Boston, MA 02114 USA. [Cetrulo, Curtis L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. [Leonard, David A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. [Leonard, David A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02129 USA. [Kurtz, Josef M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02115 USA. RP Cetrulo, CL (reprint author), Harvard Univ, Sch Med, Vascularized Composite Allotransplantat Lab, Transplantat Biol Res Ctr,Massachusetts Gen Hospi, 15 Parkman St, Boston, MA 02114 USA. EM david.leonard@tbrc.mgh.harvard.edu; josef.kurtz@tbrc.mgh.harvard.edu; ccetrulo@mgh.harvard.edu RI Brandacher, Gerald/L-7540-2016 NR 154 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4939-2071-6; 978-1-4939-2070-9 J9 STEM CELLS BIOL REG JI Stem Cell Biol. Regen. Med. PY 2015 BP 203 EP 225 DI 10.1007/978-1-4939-2071-6_15 D2 10.1007/978-1-4939-2071-6 PG 23 WC Cell & Tissue Engineering; Transplantation SC Cell Biology; Transplantation GA BE6YY UT WOS:000374950100018 ER PT S AU Tipps, ME Buck, KJ AF Tipps, Megan E. Buck, Kari J. BE Slesinger, PA Wickman, K TI GIRK Channels: A Potential Link Between Learning and Addiction SO STRUCTURE TO FUNCTION OF G PROTEIN- GATED INWARDLY RECTIFYING (GIRK) CHANNELS SE International Review of Neurobiology LA English DT Review; Book Chapter ID LONG-TERM POTENTIATION; RECTIFYING POTASSIUM CHANNELS; VENTRAL TEGMENTAL AREA; RECTIFIER K+ CHANNELS; SORTING NEXIN 27; G-BETA-GAMMA; EVOKED SYNAPTIC PLASTICITY; MEDIAL PREFRONTAL CORTEX; HUMAN-CHROMOSOME 21Q22.2; LOCUS-CERULEUS NEURONS AB The ability of drug-associated cues to reinitiate drug craving and seeking, even after long periods of abstinence, has led to the hypothesis that addiction represents a form of pathological learning, in which drugs of abuse hijack normal learning and memory processes to support long-term addictive behaviors. In this chapter, we review evidence suggesting that G protein-gated inwardly rectifying potassium (GIRK/Kir3) channels are one mechanism through which numerous drugs of abuse can modulate learning and memory processes. We will examine the role of GIRK channels in two forms of experience-dependent long-term changes in neuronal function: homeostatic plasticity and synaptic plasticity. We will also discuss how drug-induced changes in GIRK-mediated signaling can lead to changes that support the development and maintenance of addiction. C1 [Tipps, Megan E.; Buck, Kari J.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Tipps, Megan E.] Univ Minnesota, Dept Pharmacol, Minneapolis, MN 55455 USA. [Buck, Kari J.] Portland VA Med Ctr, Portland Alcohol Res Ctr, Portland, OR USA. RP Tipps, ME (reprint author), Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. EM metipps@gmail.com NR 225 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 BN 978-0-12-802631-1; 978-0-12-802458-4 J9 INT REV NEUROBIOL JI Int. Rev. Neurobiol. PY 2015 VL 123 BP 239 EP 277 DI 10.1016/bs.irn.2015.05.012 PG 39 WC Neurosciences SC Neurosciences & Neurology GA BE8BJ UT WOS:000376196400008 PM 26422987 ER PT J AU Kalore, NV Guay, J Eastman, JM Nishimori, M Singh, JA AF Kalore, Niraj V. Guay, Joanne Eastman, Jamie M. Nishimori, Mina Singh, Jasvinder A. TI Nerve blocks or no nerve blocks for pain control after elective hip replacement (arthroplasty) surgery in adults SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID PSOAS COMPARTMENT BLOCK; REGIONAL ANESTHESIA; POSTOPERATIVE ANALGESIA; SPINAL-ANESTHESIA; LUMBAR; COMPLICATIONS; METAANALYSES; GUIDELINES; EFFICACY; TRIALS C1 [Kalore, Niraj V.] Virginia Commonwealth Univ Hlth Syst, Dept Orthopaed Surg, 417 North 11th St, Richmond, VA 23298 USA. [Guay, Joanne] Univ Sherbrooke, Fac Med, Dept Anesthesiol, Rouyn Noranda, ON, Canada. [Eastman, Jamie M.] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. [Nishimori, Mina] Univ Tokyo, Dept Anesthesiol, Tokyo, Japan. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Dept Med, Birmingham, AL USA. RP Kalore, NV (reprint author), Virginia Commonwealth Univ Hlth Syst, Dept Orthopaed Surg, 417 North 11th St, Richmond, VA 23298 USA. EM niraj.kalore@gmail.com FU Takeda; Savient; Allergan; Novartis; Regeneron FX Jasvinder A Singh has received research grants from Takeda (2007 to present) and Savient (2009 to 2013; bankrupt in 2013) and consultant fees from Takeda, Allergan (2004 to 2011), Savient, Novartis, and Regeneron (2009 to 2013). He is a member of the executive committee of OMERACT, an organization that develops outcome measures in rheumatology and receives arms-length funding from 36 companies. NR 38 TC 0 Z9 0 U1 1 U2 1 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 2015 IS 3 AR CD011608 DI 10.1002/14651858.CD011608 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA DL3OC UT WOS:000375542100085 ER PT J AU Kalore, NV Guay, J Nishimori, M Eastman, JM Noorbaloochi, S Singh, JA AF Kalore, Niraj V. Guay, Joanne Nishimori, Mina Eastman, Jamie M. Noorbaloochi, Shahrzad Singh, Jasvinder A. TI Regional analgesia versus no regional analgesia for ambulatory hip arthroscopy in adults SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID PSOAS COMPARTMENT BLOCK; POSTOPERATIVE PAIN; NERVE BLOCKS; ANESTHESIA; METAANALYSES; REPLACEMENT; TRIALS C1 [Kalore, Niraj V.] Virginia Commonwealth Univ Hlth Syst, Dept Orthopaed Surg, 417 North 11th St, Richmond, VA 23298 USA. [Guay, Joanne] Univ Sherbrooke, Fac Med, Dept Anesthesiol, Sherbrooke, PQ, Canada. [Nishimori, Mina] Seibo Int Catholic Hosp, Dept Anesthesiol, Tokyo, Japan. [Eastman, Jamie M.] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. [Noorbaloochi, Shahrzad] Minneapolis VA Med Ctr, Dept Med, Minneapolis, MN USA. [Noorbaloochi, Shahrzad] Univ Minnesota, Minneapolis, MN USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Dept Med, Birmingham, AL USA. RP Kalore, NV (reprint author), Virginia Commonwealth Univ Hlth Syst, Dept Orthopaed Surg, 417 North 11th St, Richmond, VA 23298 USA. EM niraj.kalore@gmail.com FU University of Dalhousie; University of Quebec en Abitibi-Temiscamingue; Takeda; Savient; Allergan; Novartis; Regeneron FX Joanne Guay: I have had no direct relationship with any pharmaceutical company or equipment manufacturer in the past five years. I have not acted as expert witness in the past five years. I am not an author in any of the included or excluded studies. I do not hold any stock other than mutual funds. During the last five years, I have received fees as speaker for two lectures given at the University of Dalhousie: one on regional anaesthesia for carotid endarterectomy and the other on local-anaesthetic-related methaemoglobinaemia. My fees were paid by the University of Dalhousie. I am the editor of a multi author textbook on anaesthesia (including notions on general and regional anaesthesia). I will receive fees for a course on airway management at University of Quebec en Abitibi-Temiscamingue scheduled for February 2015.; Jasvinder A Singh: Jasvinder A Singh has received research grants from Takeda (2007 to present); Savient (2009 to 2013; bankrupt in 2013); and consultant fees from Takeda, Allergan (2004 to 2011); and Savient, Novartis and Regeneron (2009 to 2013); he is a member of the executive of OMERACT, an organization that develops outcome measures in rheumatology and receives arms-length funding from 36 companies. Novartis manufactures over-the-counter pain relief medication. The other companies manufacture gout drugs or Botox, which is approved for wrinkles, headaches and some other conditions. NR 27 TC 1 Z9 1 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 2015 IS 3 AR CD011578 DI 10.1002/14651858.CD011578 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA DL3OC UT WOS:000375542100064 ER PT J AU Mifflin, J AF Mifflin, Jeffrey TI Dickens and the artists SO EARLY POPULAR VISUAL CULTURE LA English DT Book Review C1 [Mifflin, Jeffrey] Massachusetts Gen Hosp, Arch & Special Collect, Boston, MA 02114 USA. RP Mifflin, J (reprint author), Massachusetts Gen Hosp, Arch & Special Collect, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1746-0654 EI 1746-0662 J9 EARLY POPUL VIS CULT JI Early Popul. Vis. Cult. PY 2015 VL 13 IS 4 SI SI BP 344 EP 346 DI 10.1080/17460654.2015.1096072 PG 3 WC Humanities, Multidisciplinary SC Arts & Humanities - Other Topics GA DK0GW UT WOS:000374591800007 ER PT J AU Morris, AC Singh, JA Bickel, CS Ponce, BA AF Morris, Andrew C. Singh, Jasvinder A. Bickel, C. Scott Ponce, Brent A. TI Exercise therapy following surgical rotator cuff repair SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID PROTOCOL; DISEASE; MOTION AB This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the benefits and harms of exercise therapy for patients following surgical repair of rotator cuff tears. To determine the optimal time post surgery for initiation of passive and active range of motion exercises. To evaluate exercise therapy versus no therapy, exercise therapy versus nonexercise modalities, and slow versus accelerated exercise therapy protocols. C1 [Morris, Andrew C.; Ponce, Brent A.] Univ Alabama Birmingham, Dept Orthopaed, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Dept Med, Fac Off Tower 805B,510 20th St South, Birmingham, AL 35294 USA. [Bickel, C. Scott] Univ Alabama Birmingham, Dept Phys Therapy, Birmingham, AL USA. RP Singh, JA (reprint author), Birmingham VA Med Ctr, Dept Med, Fac Off Tower 805B,510 20th St South, Birmingham, AL 35294 USA. EM jasvinder.md@gmail.com FU Takeda; Savient; Ardea; Regeneron; Allergan; Novartis; URL Pharmaceuticals; Arthrex; Synthes; JJ/DePuy/Mitek; Tornier FX JAS: JAS has received research grants from Takeda and Savient, and consultant fees from Ardea, Regeneron, Takeda, Allergan, Savient, Novartis, and URL Pharmaceuticals; he is a member of the executive board of OMERACT, an organization that develops outcome measures in rheumatology and receives arms-length funding from 36 companies.; BAP: BAP has received research grants from Arthrex, Synthes, J&J/DePuy/Mitek, and Tornier and is a consultant for Arthrex, Tornier, and Acumed. NR 26 TC 0 Z9 0 U1 3 U2 3 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 2015 IS 2 AR CD011531 DI 10.1002/14651858.CD011531 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA DL0TV UT WOS:000375346400055 ER PT J AU Kazemzadeh-Narbat, M Annabi, N Tamayol, A Oklu, R Ghanem, A Khademhosseini, A AF Kazemzadeh-Narbat, Mehdi Annabi, Nasim Tamayol, Ali Oklu, Rahmi Ghanem, Amyl Khademhosseini, Ali TI Adenosine-associated delivery systems SO JOURNAL OF DRUG TARGETING LA English DT Review DE Adenosine; controlled drug delivery; controlled release; drug delivery; drug targeting; nanoparticles; targeted drug delivery ID IMPLANT-ASSOCIATED INFECTIONS; TEMPORAL-LOBE EPILEPSY; STEM-CELL GRAFTS; DRUG-DELIVERY; SILK FIBROIN; POLYETHYLENE-GLYCOL; IN-VITRO; CONTROLLED-RELEASE; ANTIMICROBIAL PEPTIDES; DEAMINASE DEFICIENCY AB Adenosine is a naturally occurring purine nucleoside in every cell. Many critical treatments such as modulating irregular heartbeat (arrhythmias), regulation of central nervous system (CNS) activity and inhibiting seizural episodes can be carried out using adenosine. Despite the significant potential therapeutic impact of adenosine and its derivatives, the severe side effects caused by their systemic administration have significantly limited their clinical use. In addition, due to adenosine's extremely short half-life in human blood (<10 s), there is an unmet need for sustained delivery systems to enhance efficacy and reduce side effects. In this article, various adenosine delivery techniques, including encapsulation into biodegradable polymers, cell-based delivery, implantable biomaterials and mechanical-based delivery systems, are critically reviewed and the existing challenges are highlighted. C1 [Kazemzadeh-Narbat, Mehdi; Annabi, Nasim; Tamayol, Ali; Khademhosseini, Ali] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Biomed Engn,Dept Med,Biomat Innovat Res Ctr, Boston, MA 02115 USA. [Kazemzadeh-Narbat, Mehdi; Annabi, Nasim; Tamayol, Ali; Khademhosseini, Ali] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Kazemzadeh-Narbat, Mehdi; Ghanem, Amyl] Dalhousie Univ, Dept Proc Engn & Appl Sci, Halifax, NS B3H 4R2, Canada. [Annabi, Nasim; Khademhosseini, Ali] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Annabi, Nasim] Northeastern Univ, Dept Chem Engn, Boston, MA 02115 USA. [Oklu, Rahmi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Intervent Radiol, Boston, MA USA. [Khademhosseini, Ali] King Abdulaziz Univ, Dept Phys, Jeddah 21413, Saudi Arabia. RP Khademhosseini, A (reprint author), 65 Landsdowne St,Room 265, Cambridge, MA 02139 USA. EM amyl.ghanem@dal.ca; akhademhosseini@rics.bwh.harvard.edu OI Khademhosseini, Ali/0000-0001-6322-8852 FU National Science Foundation [EFRI-1240443]; IMMODGEL [602694]; National Institutes of Health [EB012597, AR057837, DE021468, HL099073, AI105024, AR063745] FX The authors acknowledge funding from the National Science Foundation (EFRI-1240443), IMMODGEL (602694), and the National Institutes of Health (EB012597, AR057837, DE021468, HL099073, AI105024, AR063745). NR 192 TC 0 Z9 0 U1 1 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1061-186X EI 1029-2330 J9 J DRUG TARGET JI J. Drug Target. PY 2015 VL 23 IS 7-8 BP 580 EP 596 DI 10.3109/1061186X.2015.1058803 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DK2UF UT WOS:000374769200003 PM 26453156 ER PT J AU Markowitz, JT Garvey, KC Laffel, LMB AF Markowitz, Jessica T. Garvey, Katharine C. Laffel, Lori M. B. TI Developmental Changes in the Roles of Patients and Families in Type 1 Diabetes Management SO CURRENT DIABETES REVIEWS LA English DT Article DE Type 1 diabetes; pediatrics; intensive therapy; family teamwork; adolescence; transition ID RANDOMIZED CONTROLLED-TRIAL; GLUCOSE MONITORING ADHERENCE; EXCHANGE CLINIC REGISTRY; GLYCEMIC CONTROL; SELF-CARE; MICROVASCULAR COMPLICATIONS; METABOLIC-CONTROL; YOUNG-CHILDREN; PARENTAL INVOLVEMENT; BEHAVIOR-THERAPY AB Developmentally-tailored diabetes self-care education and support are integral parts of contemporary multidisciplinary T1D care. The patient with T1D must have the support of the family and the diabetes team to maintain the rigors of diabetes management, but the specific roles of patients and families with regard to daily diabetes tasks change considerably throughout the developmental span of early childhood, middle childhood/school-age years, and adolescence. This review provides a framework of key normative developmental issues for each of these developmental stages. Within this context, ideal family diabetes management is reviewed within each developmental stage and anticipated challenges that can arise during these stages and that can adversely impact diabetes management are presented. This paper also summarizes empirical evidence for specific intervention and care strategies to support optimal diabetes management across these stages in order to maximize opportunities for a successful transfer of diabetes management tasks from parents to maturing youth. Finally, the review provides an emphasis on approaches to promote family teamwork and adolescent diabetes self-care adherence as well as opportunities to use novel technology platforms as a means to support optimal diabetes management. C1 [Markowitz, Jessica T.; Laffel, Lori M. B.] Joslin Diabet Ctr, Pediat Adolescent & Youth Adult Sect, Boston, MA 02215 USA. [Garvey, Katharine C.] Boston Childrens Hosp, Div Endocrinol, Boston, MA USA. [Markowitz, Jessica T.; Laffel, Lori M. B.] Joslin Diabet Ctr, Pediat Adolescent & Youth Adult Sect, Genet & Epidemiol Sect, Boston, MA 02215 USA. RP Markowitz, JT (reprint author), Joslin Diabet Ctr, Pediat Adolescent & Youth Adult Sect, Boston, MA 02215 USA. EM jessica.markowitz@joslin.harvard.edu FU NIDDK NIH HHS [R01 DK095273, K12 DK094721, K12DK094721, K23 DK092335, K23 DK102655, K23DK092335, K23DK102655, P30 DK036836, P30DK036836, R01DK095273] NR 75 TC 3 Z9 3 U1 10 U2 12 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1573-3998 EI 1875-6417 J9 CURR DIABETES REV JI Curr. Diabetes Reviews PY 2015 VL 11 IS 4 BP 231 EP 238 DI 10.2174/1573399811666150421114146 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DJ6DN UT WOS:000374300300004 PM 25901503 ER PT J AU D'Andrea, A La Gerche, A Golia, E Teske, AJ Bossone, E Russo, MG Calabro, R Baggish, AL AF D'Andrea, Antonello La Gerche, Andre Golia, Enrica Teske, Arco J. Bossone, Eduardo Russo, Maria Giovanna Calabro, Raffaele Baggish, Aaron L. TI Right Heart Structural and Functional Remodeling in Athletes SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Article DE athlete's heart; echocardiography; exercise; right ventricle; strain imaging; tissue Doppler ID RIGHT-VENTRICULAR FUNCTION; MYOCARDIAL PERFORMANCE INDEX; ECHOCARDIOGRAPHIC-ASSESSMENT; HYPERTROPHIC CARDIOMYOPATHY; SYSTOLIC FUNCTION; CARDIAC STRUCTURE; MARATHON RUNNERS; EUROPEAN-SOCIETY; HEALTHY-SUBJECTS; SUDDEN-DEATH AB Long-term intensive exercise training programs lead to numerous progressive cardiac adaptations, which are collectively termed "athlete's heart." Noninvasive diagnostic techniques, such as color Doppler echocardiography, have been widely used in the analysis of the athlete's heart. Initial experiences focused mainly on left heart adaptations to training. However, in recent years, substantial structural and functional adaptations of the right heart have been documented. The present review article focuses on recent data defining right heart adaptation to short-and long-term periods of exercise training. Right ventricular (RV) morphology and function may be more profoundly affected by intense exercise and, in some cases, functional recovery may be incomplete. Moreover, there is speculation that such changes may represent a substrate for proarrhythmic RV remodeling in some highly trained athletes, even in the absence of a known familial redisposition. C1 [D'Andrea, Antonello; Golia, Enrica; Russo, Maria Giovanna; Calabro, Raffaele] Univ Naples 2, Chair Cardiol, Naples, Italy. [La Gerche, Andre] Univ Melbourne, Dept Med, St Vincents Hosp, Melbourne, Vic, Australia. [Teske, Arco J.] Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands. [Bossone, Eduardo] Policlin San Donato, IRCCS, Dept Cardiac Surg, Milan, Italy. [Baggish, Aaron L.] Massachusetts Gen Hosp, Cardiovasc Performance Program, Boston, MA 02114 USA. RP D'Andrea, A (reprint author), Via M Schipa 44, I-80122 Naples, Italy. EM antonellodandrea@libero.it OI Calabro, Raffaele/0000-0001-9546-8914; RUSSO, Maria Giovanna/0000-0003-3860-6158 NR 80 TC 4 Z9 4 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0742-2822 EI 1540-8175 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD JAN PY 2015 VL 32 SU 1 SI SI BP 11 EP 22 DI 10.1111/echo.12226 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CA4FY UT WOS:000348861000003 PM 25244243 ER PT J AU Wynn, JK Jimenez, AM Roach, BJ Korb, A Lee, J Horan, WP Ford, JM Green, MF AF Wynn, Jonathan K. Jimenez, Amy M. Roach, Brian J. Korb, Alexander Lee, Junghee Horan, William P. Ford, Judith M. Green, Michael F. TI Impaired target detection in schizophrenia and the ventral attentional network: Findings from a joint event-related potential-functional MRI analysis Target stimulus ERP/fMRI analysis in schizophrenia SO NEUROIMAGE-CLINICAL LA English DT Article DE ERP; fMRI; Joint ICA; Oddball; Salience network ID SUSTAINED ATTENTION; P300; FMRI; METAANALYSIS; SALIENCE; INFORMATION; BRAIN; TASK; CONNECTIVITY; DYSFUNCTION AB Schizophrenia patients have abnormal neural responses to salient, infrequent events. We integrated event-related potentials (ERP) and fMRI to examine the contributions of the ventral (salience) and dorsal (sustained) attention networks to this dysfunctional neural activation. Twenty-one schizophrenia patients and 22 healthy controls were assessed in separate sessions with ERP and fMRI during a visual oddball task. Visual P100, N100, and P300 ERP waveforms and fMRI activation were assessed. A joint independent components analysis (jICA) on the ERP and fMRI data were conducted. Patients exhibited reduced P300, but not P100 or N100, amplitudes to targets and reduced fMRI neural activation in both dorsal and ventral attentional networks compared with controls. However, the jICA revealed that the P300 was linked specifically to activation in the ventral (salience) network, including anterior cingulate, anterior insula, and temporal parietal junction, with patients exhibiting significantly lower activation. The P100 and N100 were linked to activation in the dorsal (sustained) network, with no group differences in level of activation. This joint analysis approach revealed the nature of target detection deficits that were not discernable by either imaging methodology alone, highlighting the utility of a multimodal fMRI and ERP approach to understand attentional network deficits in schizophrenia. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). C1 [Wynn, Jonathan K.; Jimenez, Amy M.; Lee, Junghee; Horan, William P.; Green, Michael F.] MIRECC, Vet Affairs Greater Los Angeles Healthcare Syst, Bldg 210,Room 131,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. [Wynn, Jonathan K.; Korb, Alexander; Lee, Junghee; Horan, William P.; Green, Michael F.] Univ Calif Los Angeles, Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Roach, Brian J.; Ford, Judith M.] Northern Calif Inst Res & Educ, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. [Ford, Judith M.] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. RP Wynn, JK (reprint author), MIRECC, Vet Affairs Greater Los Angeles Healthcare Syst, Bldg 210,Room 131,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jkwynn@ucla.edu RI Wynn, Jonathan/H-3749-2014; Lee, Junghee/C-5226-2014 OI Wynn, Jonathan/0000-0002-1763-8540; Lee, Junghee/0000-0001-9567-8700 FU Veterans Affairs (VA) Career Development Award [Wynn 0001]; VA Merit Review Grant [I01CX000497]; National Institutes of Mental Health [MH58262, MH43292, MH065707]; Brain Mapping Medical Research Organization; Brain Mapping Support Foundation; Pierson-Lovelace Foundation; 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; Northstar Fund FX This work was supported by a Veterans Affairs (VA) Career Development Award (Wynn 0001) to JKW; VA Merit Review Grant (I01CX000497) and National Institutes of Mental Health (MH58262) to JMF; and National Institutes of Mental Health grants MH43292 and MH065707 to MFG. 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 funding sources had no role in: the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 50 TC 6 Z9 6 U1 2 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2015 VL 9 BP 95 EP 102 DI 10.1016/j.nicl.2015.07.004 PG 8 WC Neuroimaging SC Neurosciences & Neurology GA DI0LR UT WOS:000373188400012 PM 26448909 ER PT J AU Holt, DJ Boeke, EA Coombs, G DeCross, SN Cassidy, BS Stufflebeam, S Rauch, SL Tootell, RBH AF Holt, Daphne J. Boeke, Emily A. Coombs, Garth, III DeCross, Stephanie N. Cassidy, Brittany S. Stufflebeam, Steven Rauch, Scott L. Tootell, Roger B. H. TI Abnormalities in personal space and parietal-frontal function in schizophrenia SO NEUROIMAGE-CLINICAL LA English DT Article DE Schizophrenia; Personal space; Faces; Object processing; Parietal cortex; Premotor cortex ID SOCIAL NETWORK SIZE; FUSIFORM FACE AREA; 1ST-EPISODE SCHIZOPHRENIA; INTERPERSONAL DISTANCE; NEGATIVE SYNDROME; BRAIN ACTIVATION; PREMOTOR CORTEX; FMRI; DYSFUNCTION; COGNITION AB Schizophrenia is associated with subtle abnormalities in day-to-day social behaviors, including a tendency in some patients to "keep their distance" from others in physical space. The neural basis of this abnormality, and related changes in social functioning, is unknown. Here we examined, in schizophrenic patients and healthy control subjects, the functioning of a parietal-frontal network involved in monitoring the space immediately surrounding the body ("personal space"). Using fMRI, we found that one region of this network, the dorsal intraparietal sulcus (DIPS), was hyper-responsive in schizophrenic patients to face stimuli appearing to move towards the subjects, intruding into personal space. This hyper-responsivity was predicted both by the size of personal space (which was abnormally elevated in the schizophrenia group) and the severity of negative symptoms. In contrast, in a second study, the activity of two lower-level visual areas that send information to DIPS (the fusiform face area and middle temporal area) was normal in schizophrenia. Together, these findings suggest that changes in parietal-frontal networks that support the sensory-guided initiation of behavior, including actions occurring in the space surrounding the body, contribute to social dysfunction and negative symptoms in schizophrenia. (C) 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). C1 [Holt, Daphne J.; Boeke, Emily A.; Coombs, Garth, III; DeCross, Stephanie N.; Cassidy, Brittany S.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Holt, Daphne J.; Stufflebeam, Steven; Rauch, Scott L.; Tootell, Roger B. H.] Harvard Univ, Sch Med, Boston, MA USA. [Holt, Daphne J.; Boeke, Emily A.; Coombs, Garth, III; DeCross, Stephanie N.; Cassidy, Brittany S.; Stufflebeam, Steven; Tootell, Roger B. H.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Stufflebeam, Steven] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Rauch, Scott L.] McLean Hosp, Belmont, MA 02178 USA. RP Holt, DJ (reprint author), 149 13th St, Charlestown, MA 02129 USA. EM dholt@partners.org; emilyboeke@nyu.edu; gcoombs@nmr.mgh.harvard.edu; sdecross@mgh.harvard.edu; britcass@gmail.com; smstufflebeam@mgh.harvard.edu; srauch@partners.org; tootell@nmr.mgh.harvard.edu FU National Institute of Mental Health [K23MH076054]; NARSAD Independent Investigator Award; Martinos Center [1S10RR023043, 1S10RR023401] FX This work was supported by the National Institute of Mental Health K23MH076054 (DJH) and a NARSAD Independent Investigator Award (RBHT), as well as by grants (1S10RR023043 and 1S10RR023401) for shared resources provided by the Martinos Center. NR 71 TC 3 Z9 3 U1 3 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2015 VL 9 BP 233 EP 243 DI 10.1016/j.nicl.2015.07.008 PG 11 WC Neuroimaging SC Neurosciences & Neurology GA DI0LR UT WOS:000373188400026 PM 26484048 ER PT J AU Egorova, N Gollub, RL Kong, J AF Egorova, Natalia Gollub, Randy L. Kong, Jian TI Repeated verumbut not placebo acupuncture normalizes connectivity in brain regions dysregulated in chronic pain SO NEUROIMAGE-CLINICAL LA English DT Article DE Acupuncture; Resting state fMRI; Chronic pain; Osteoarthritis ID CHRONIC KNEE PAIN; LOW-BACK-PAIN; PERIAQUEDUCTAL GRAY; FUNCTIONAL CONNECTIVITY; PREFRONTAL CORTEX; RANDOMIZED-TRIAL; OSTEOARTHRITIS; ANALGESIA; NETWORK; METAANALYSIS AB Acupuncture, an ancient East Asian therapy, is aimed at rectifying the imbalance within the body caused by disease. Studies evaluating the efficacy of acupuncture with neuroimaging tend to concentrate on brain regions within the painmatrix, associated with acute pain. We, however, focused on the effect of repeated acupuncture treatment specifically on brain regions known to support functions dysregulated in chronic pain disorders. Transition to chronic pain is associated with increased attention to pain, emotional rumination, nociceptive memory and avoidance learning, resulting in brain connectivity changes, specifically affecting the periaqueductal gray (PAG), medial frontal cortex (MFC) and bilateral hippocampus (Hpc). We demonstrate that the PAG-MFC and PAG-Hpc connectivity in patients with chronic pain due to knee osteoarthritis indeed correlates with clinical severity scores and further show that verum acupuncture-induced improvement in pain scores (compared to sham) is related to the modulation of PAG-MFC and PAG-Hpc connectivity in the predicted direction. This study shows that repeated verum acupuncture might act by restoring the balance in the connectivity of the key pain brain regions, altering pain-related attention and memory. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Egorova, Natalia; Gollub, Randy L.; Kong, Jian] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Bldg 120,2nd Ave,Suite 101C, Charlestown, MA USA. RP Kong, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Bldg 120,2nd Ave,Suite 101C, Charlestown, MA USA. EM kongj@nmr.mgh.harvard.edu OI Egorova, Natalia/0000-0002-9244-2900 FU NCCIH [R21AT004497, RO1AT00634, R01AT008563, RO1AT005280, P01AT006663] FX This work was supported by R21AT004497 (NCCIH), RO1AT00634 and R01AT008563 (NCCIH) to Jian Kong, RO1AT005280 (NCCIH) to Randy Gollub, and P01AT006663 to Bruce Rosen. The authors declare no conflict of interest. NR 56 TC 5 Z9 5 U1 2 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2015 VL 9 BP 430 EP 435 DI 10.1016/j.nicl.2015.09.012 PG 6 WC Neuroimaging SC Neurosciences & Neurology GA DI0LR UT WOS:000373188400046 PM 26594625 ER PT J AU Simard, I Luck, D Mottron, L Zeffiro, TA Soulieres, I AF Simard, Isabelle Luck, David Mottron, Laurent Zeffiro, Thomas A. Soulieres, Isabelle TI Autistic fluid intelligence: Increased reliance on visual functional connectivity with diminished modulation of coupling by task difficulty SO NEUROIMAGE-CLINICAL LA English DT Article DE Autism; fMRI; Reasoning; Connectivity; PPI; Intelligence ID STANDARD PROGRESSIVE MATRICES; WHITE-MATTER; PREFRONTAL CORTEX; SPECTRUM DISORDER; INNER SPEECH; BRAIN; UNDERCONNECTIVITY; METAANALYSIS; RECRUITMENT; INTEGRATION AB Different test types lead to different intelligence estimates in autism, as illustrated by the fact that autistic individuals obtain higher scores on the Raven's Progressive Matrices (RSPM) test than they do on the Wechsler IQ, in contrast to relatively similar performance on both tests in non-autistic individuals. However, the cerebral processes underlying these differences are not well understood. This study investigated whether activity in the fluid "reasoning" network, which includes frontal, parietal, temporal and occipital regions, is differently modulated by task complexity in autistic and non-autistic individuals during the RSPM. In this purpose, we used fMRI to study autistic and non-autistic participants solving the 60 RSPM problems focussing on regions and networks involved in reasoning complexity. As complexity increased, activity in the left superior occipital gyrus and the left middle occipital gyrus increased for autistic participants, whereas non-autistic participants showed increased activity in the left middle frontal gyrus and bilateral precuneus. Using psychophysiological interaction analyses (PPI), we then verified in which regions did functional connectivity increase as a function of reasoning complexity. PPI analyses revealed greater connectivity in autistic, compared to non-autistic participants, between the left inferior occipital gyrus and areas in the left superior frontal gyrus, right superior parietal lobe, right middle occipital gyrus and right inferior temporal gyrus. We also observed generally less modulation of the reasoning network as complexity increased in autistic participants. These results suggest that autistic individuals, when confrontedwith increasing task complexity, rely mainly on visuospatial processes when solving more complex matrices. In addition to the now well-established enhanced activity observed in visual areas in a range of tasks, these results suggest that the enhanced reliance on visual perception has a central role in autistic cognition. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Simard, Isabelle] Univ Montreal, Dept Psychol, Montreal, PQ H3C 3J7, Canada. [Simard, Isabelle; Luck, David; Mottron, Laurent; Soulieres, Isabelle] Inst Univ Sante Mentale Montreal, Res Ctr, Montreal, PQ H1N 3M5, Canada. [Luck, David; Mottron, Laurent] Univ Montreal, Dept Psychiat, Fac Med, Montreal, PQ H3C 3J7, Canada. [Zeffiro, Thomas A.] Massachusetts Gen Hosp, Neural Syst Grp, Charlestown, MA 02129 USA. [Soulieres, Isabelle] Univ Quebec, Dept Psychol, CP 8888,Succ Ctr Ville, Montreal, PQ H3C 3P8, Canada. RP Soulieres, I (reprint author), Univ Quebec, Dept Psychol, CP 8888,Succ Ctr Ville, Montreal, PQ H3C 3P8, Canada. EM soulieres.isabelle@uqam.ca NR 53 TC 4 Z9 4 U1 9 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2015 VL 9 BP 467 EP 478 DI 10.1016/j.nicl.2015.09.007 PG 12 WC Neuroimaging SC Neurosciences & Neurology GA DI0LR UT WOS:000373188400050 PM 26594629 ER PT J AU Levman, J Takahashi, E AF Levman, Jacob Takahashi, Emi TI Multivariate analyses applied to fetal, neonatal and pediatric MRI of neurodevelopmental disorders SO NEUROIMAGE-CLINICAL LA English DT Review DE Multivariate analysis; Machine learning; Fetal; Neonatal; Pediatric; Brain MRI ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; OBSESSIVE-COMPULSIVE DISORDER; AUTISM SPECTRUM DISORDER; SUPPORT VECTOR MACHINE; MAGNETIC-RESONANCE; WHITE-MATTER; PATTERN-CLASSIFICATION; BIPOLAR DISORDER; RESTING-STATE; DISCRIMINATIVE ANALYSIS AB Multivariate analysis (MVA) is a class of statistical and pattern recognition methods that involve the processing of data that contains multiple measurements per sample. MVA can be used to address a wide variety of medical neuroimaging-related challenges including identifying variables associated with a measure of clinical importance (i.e. patient outcome), creating diagnostic tests, assisting in characterizing developmental disorders, understanding disease etiology, development and progression, assisting in treatment monitoring and much more. Compared to adults, imaging of developing immature brains has attracted less attention from MVA researchers. However, remarkable MVA research growth has occurred in recent years. This paper presents the results of a systematic review of the literature focusing on MVA technologies applied to neurodevelopmental disorders in fetal, neonatal and pediatric magnetic resonance imaging (MRI) of the brain. The goal of this manuscript is to provide a concise review of the state of the scientific literature on studies employing brain MRI and MVA in a pre-adult population. Neurological developmental disorders addressed in the MVA research contained in this review include autism spectrum disorder, attention deficit hyperactivity disorder, epilepsy, schizophrenia and more. While the results of this review demonstrate considerable interest from the scientific community in applications of MVA technologies in pediatric/neonatal/fetal brain MRI, the field is still young and considerable research growth remains ahead of us. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Levman, Jacob; Takahashi, Emi] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Newborn Med,Dept Med, 1 Autumn St 456, Boston, MA 02115 USA. [Levman, Jacob; Takahashi, Emi] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Levman, J (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Div Newborn Med,Dept Med, 1 Autumn St 456, Boston, MA 02115 USA. EM jacob.levman@childrens.harvard.edu FU National Institute of Health [R01HD078561, R03NS091587] FX This article was supported financially by the National Institute of Health grants R01HD078561 and R03NS091587 to ET. NR 139 TC 1 Z9 1 U1 6 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2015 VL 9 BP 532 EP 544 DI 10.1016/j.nicl.2015.09.017 PG 13 WC Neuroimaging SC Neurosciences & Neurology GA DI0LR UT WOS:000373188400057 PM 26640765 ER PT J AU Desbordes, G Li, A Loggia, ML Kim, J Schalock, PC Lerner, E Tran, TN Ring, J Rosen, BR Kaptchuk, TJ Pfab, F Napadow, V AF Desbordes, Galle Li, Ang Loggia, Marco L. Kim, Jieun Schalock, Peter C. Lerner, Ethan Tran, Thanh N. Ring, Johannes Rosen, Bruce R. Kaptchuk, Ted J. Pfab, Florian Napadow, Vitaly TI Evoked itch perception is associated with changes in functional brain connectivity SO NEUROIMAGE-CLINICAL LA English DT Article DE Atopic dermatitis; Eczema; Insula; Pruritus; Putamen ID HISTAMINE-INDUCED ITCH; SURFACE-BASED ANALYSIS; ATOPIC-DERMATITIS; NERVOUS-SYSTEM; NEURAL MECHANISMS; DISEASE SEVERITY; CROSSOVER TRIAL; SOCIAL-FACTORS; CLINICAL PAIN; MRI AB Chronic itch, a highly debilitating condition, has received relatively little attention in the neuroimaging literature. Recent studies suggest that brain regions supporting itch in chronic itch patients encompass sensorimotor and salience networks, and corticostriatal circuits involved in motor preparation for scratching. However, how these different brain areas interact with one another in the context of itch is still unknown. We acquired BOLD fMRI scans in 14 atopic dermatitis patients to investigate resting-state functional connectivity before and after allergen-induced itch exacerbated the clinical itch perception in these patients. A seed-based analysis revealed decreased functional connectivity from baseline resting state to the evoked-itch state between several itch related brain regions, particularly the insular and cingulate cortices and basal ganglia, where decreased connectivity was significantly correlated with increased levels of perceived itch. In contrast, evoked itch increased connectivity between key nodes of the frontoparietal control network (superior parietal lobule and dorsolateral prefrontal cortex), where higher increase in connectivity was correlated with a lesser increase in perceived itch, suggesting that greater interaction between nodes of this executive attention network serves to limit itch sensation via enhanced top-down regulation. Overall, our results provide the first evidence of itch-dependent changes in functional connectivity across multiple brain regions. (C) 2014 The Authors. Published by Elsevier Inc C1 [Desbordes, Galle; Li, Ang; Loggia, Marco L.; Kim, Jieun; Rosen, Bruce R.; Pfab, Florian; Napadow, Vitaly] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. [Napadow, Vitaly] Logan Coll Chiropract, Dept Radiol, Chesterfield, MO USA. [Schalock, Peter C.; Lerner, Ethan; Tran, Thanh N.] Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Kaptchuk, Ted J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Internal Med, Boston, MA 02215 USA. [Ring, Johannes; Pfab, Florian] Tech Univ Munich, Dept Dermatol & Allergy, D-80290 Munich, Germany. [Pfab, Florian] Tech Univ Munich, Dept Prevent & Sports Med, D-80290 Munich, Germany. [Napadow, Vitaly] Kyung Hee Univ, Dept Biomed Engn, Yongin, South Korea. RP Desbordes, G (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Suite 2301,149 Thirteenth St, Boston, MA 02129 USA. EM gdesbord@nmr.mgh.harvard.edu FU National Institutes of Health [K01AT002166, R01AT004714, K01AT008225, P01AT002048, K24AT004095, R01AR057744]; Center for Functional Neuroimaging Technologies, National Institute of Biomedical Imaging and Bio-engineering (NIBIB), National Institutes of Health [P41EB015896]; NIH Shared Instrumentation Grant Program [S10RR021110, S10OD010364, S10RR023401]; German Research Foundation [pf 690/2-1] FX This work was supported by the National Institutes of Health (V.N.: K01AT002166, R01AT004714; G.D.: K01AT008225; B.R.R: P01AT002048; T.K.: K24AT004095; E.L.: R01AR057744). 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, P41EB015896, a P41 Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bio-engineering (NIBIB), National Institutes of Health. This work also involved the use of instrumentation supported by the NIH Shared Instrumentation Grant Program S10RR021110, S10OD010364, and S10RR023401. This study was also partly funded by a grant from the German Research Foundation (pf 690/2-1; http://www.dfg.de/en/research_funding/), and the Christine Kuhne Center of Allergy and Education (CK-Care; http://www.ck-care.ch/index.php?id=2659&L=4). NR 83 TC 2 Z9 3 U1 2 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2015 VL 7 BP 213 EP 221 DI 10.1016/j.nicl.2014.12.002 PG 9 WC Neuroimaging SC Neurosciences & Neurology GA DI0GE UT WOS:000373172600024 PM 25610783 ER PT J AU Michalska, KJ Decety, J Zeffiro, TA Lahey, BB AF Michalska, Kalina J. Decety, Jean Zeffiro, Thomas A. Lahey, Benjamin B. TI Association of regional gray matter volumes in the brain with disruptive behavior disorders in male and female children SO NEUROIMAGE-CLINICAL LA English DT Article DE Childhood-onset conduct disorder; Voxel-based morphometry; Gray matter; Superior temporal sulcus ID CALLOUS-UNEMOTIONAL TRAITS; VOXEL-BASED MORPHOMETRY; ONSET CONDUCT DISORDER; OPPOSITIONAL DEFIANT DISORDER; SUPERIOR TEMPORAL SULCUS; STRUCTURE ABNORMALITIES; ANTISOCIAL PERSONALITY; GENDER-DIFFERENCES; SEX-DIFFERENCES; GREY-MATTER AB Because the disruptive behavior disorders are highly impairing conditions, it is important to determine if structural variations in brain arc associated early in life with these problems among children. Structural MRI data were acquired from 111 9-11 year olds (58 girls and 53 boys), 43 who met diagnostic criteria for oppositional defiant disorder anti or conduct disorder and 68 healthy controls. Voxel-basecl morphometry was used to examine associations of behavioral measures with gray matter volumes in whole-brain analyses. Unlike previous studies, variation in gray matter volume was not found to be associated with a disruptive behavior disorder diagnosis in any brain region at p <.05 with EWE correction. Nonetheless, an inverse nonlinear association of the number of conduct disorder (CD) symptoms with gray matter volume along the left superior temporal sulcus was significant in the full sample (p <.05 with FINE correction), with a trend in the right hemisphere (p < 0.001 uncorrected). There also was a trend toward a stronger association of the number of CD symptoms with gray matter volume along the left superior temporal sulcus in girls than boys. The present findings did not replicate previous findings of reduced gray matter volumes in the anterior insula, amygdala, and frontal cortex in youth with CD, but are consistent with previous findings of reduced gray matter volumes in temporal regions, particularly in girls, (C) 2014 The Authors. Published by Elsevier Inc. C1 [Michalska, Kalina J.; Decety, Jean] Univ Chicago, Dept Psychol, 5848 S Univ Ave, Chicago, IL 60637 USA. [Decety, Jean] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA. [Zeffiro, Thomas A.] Massachusetts Gen Hosp, Neural Syst Grp, Charlestown, MA USA. [Lahey, Benjamin B.] Univ Chicago, Dept Publ Hlth Sci, Chicago, IL 60637 USA. RP Lahey, BB (reprint author), Univ Chicago, Dept Publ Hlth Sci, Chicago, IL 60637 USA. EM blahey@uchicago.edu FU NIMH [R01-MH084934] FX This study was supported by NIMH grant R01-MH084934. We thank Carrie Swetlik for her assistance with data collection and management. NR 67 TC 6 Z9 6 U1 3 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2015 VL 7 BP 252 EP 257 DI 10.1016/j.nicl.2014.12.012 PG 6 WC Neuroimaging SC Neurosciences & Neurology GA DI0GE UT WOS:000373172600028 PM 25610787 ER PT J AU Barron, DS Fox, PT Pardoe, H Lancaster, J Price, LR Blackmon, K Berry, K Cavazos, JE Kuzniecky, R Devinsky, O Thesen, T AF Barron, Daniel S. Fox, Peter T. Pardoe, Heath Lancaster, Jack Price, Larry R. Blackmon, Karen Berry, Kristen Cavazos, Jose E. Kuzniecky, Ruben Devinsky, Orrin Thesen, Thomas TI Thalamic functional connectivity predicts seizure laterality in individual TLE patients: Application of a biomarker development strategy SO NEUROIMAGE-CLINICAL LA English DT Article DE Epilepsy; Temporal Lobe Epilepsy; Thalamus; Resting-state fMRI; fMRI; Biomarker; Lateralization ID TEMPORAL-LOBE EPILEPSY; NETWORKS; MRI; ORGANIZATION; BRAIN AB Noninvasive markers of brain function could yield biomarkers in many neurological disorders. Disease models constrained by coordinate-based meta-analysis are likely to increase this yield. Here, we evaluate a thalamic model of temporal lobe epilepsy that we proposed in a coordinate-based meta-analysis and extended in a diffusion tractography study of an independent patient population. Specifically, we evaluated whether thalamic functional connectivity (resting-state fMRI-BOLD) with temporal lobe areas can predict seizure onset laterality, as established with intracranial EEG. Twenty-four lesional and non-lesional temporal lobe epilepsy patients were studied. No significant differences in functional connection strength in patient and control groups were observed with Mann-Whitney Tests (corrected for multiple comparisons). Notwithstanding the lack of group differences, individual patient difference scores (from control mean connection strength) successfully predicted seizure onset zone as shown in ROC curves: discriminant analysis (two-dimensional) predicted seizure onset zone with 85% sensitivity and 91% specificity; logistic regression (four-dimensional) achieved 86% sensitivity and 100% specificity. The strongest markers in both analyses were left thalamo-hippocampal and right thalamo-entorhinal cortex functional connection strength. Thus, this study shows that thalamic functional connections are sensitive and specific markers of seizure onset laterality in individual temporal lobe epilepsy patients. This study also advances an overall strategy for the programmatic development of neuroimaging biomarkers in clinical and genetic populations: a disease model informed by coordinate-based meta-analysis was used to anatomically constrain individual patient analyses. (C) 2014 The Authors. Published by Elsevier Inc. C1 [Barron, Daniel S.; Fox, Peter T.; Lancaster, Jack] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, San Antonio, TX 78229 USA. [Barron, Daniel S.] Yale Univ, Sch Med, New Haven, CT USA. [Fox, Peter T.; Lancaster, Jack] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Fox, Peter T.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Fox, Peter T.; Cavazos, Jose E.] Univ TX Hlth Sci Ctr, Dept Neurol, San Antonio, TX USA. [Fox, Peter T.] Univ Hong Kong, State Key Lab Brain & Cognit Sci, Hong Kong, Hong Kong, Peoples R China. [Pardoe, Heath; Blackmon, Karen; Berry, Kristen; Kuzniecky, Ruben; Devinsky, Orrin; Thesen, Thomas] NYU, Dept Neurol, New York, NY 10016 USA. [Price, Larry R.] Texas State Univ, Coll Educ, San Marcos, TX USA. [Price, Larry R.] Texas State Univ, Coll Sci, San Marcos, TX USA. [Cavazos, Jose E.] South Texas Vet Hlth Care Syst, San Antonio Epilepsy Ctr Excellence, San Antonio, TX USA. RP Barron, DS (reprint author), Off Student Affairs, 367 Cedar St, New Haven, CT 06510 USA. EM daniel.s.barron@yale.edu RI Cavazos, Jose/J-4122-2016; OI Cavazos, Jose/0000-0001-5777-2608; Devinsky, Orrin/0000-0003-0044-4632; Pardoe, Heath/0000-0002-0123-2167 FU National Institute of Neurological Disorder Stroke [1-F31-NS083160-01]; National Institute of Health [RO1 MH074457]; F.A.C.E.S (Finding a cure for epilepsy and Seizures); American Epilepsy Foundation FX Funding from the National Institute of Neurological Disorder & Stroke1-F31-NS083160-01 (D.S.B.), National Institute of HealthRO1 MH074457 (P.T.F.), F.A.C.E.S (Finding a cure for epilepsy and Seizures; T.T., O.D.) and the American Epilepsy Foundation (T.T.) assisted in the collection, management, analysis, and interpretation of the data; and in the preparation and review of the manuscript. NR 29 TC 5 Z9 5 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2015 VL 7 BP 273 EP 280 DI 10.1016/j.nicl.2014.08.002 PG 8 WC Neuroimaging SC Neurosciences & Neurology GA DI0GE UT WOS:000373172600031 PM 25610790 ER PT J AU Zurcher, NR Loggia, ML Lawson, R Chonde, DB Izquierdo-Garcia, D Yasek, JE Akeju, O Catana, C Rosen, BR Cudkowicz, ME Hooker, JM Atassi, N AF Zuercher, Nicole R. Loggia, Marco L. Lawson, Robert Chonde, Daniel B. Izquierdo-Garcia, David Yasek, Julia E. Akeju, Oluwaseun Catana, Ciprian Rosen, Bruce R. Cudkowicz, Merit E. Hooker, Jacob M. Atassi, Nazem TI Increased in vivo glial activation in patients with amyotrophic lateral sclerosis: Assessed with [C-11]-PBR28 SO NEUROIMAGE-CLINICAL LA English DT Article DE Amyotrophic lateral sclerosis; Positron emission tomography; [C-11]PBR-28; Neuroinflammation; Microglia; Motor cortex ID POSITRON-EMISSION-TOMOGRAPHY; SPINAL-CORD TISSUE; PROTEIN 18 KDA; PET RADIOLIGAND; BRAIN; ALS; TSPO; INFLAMMATION; POLYMORPHISM; C-11-PBR28 AB Evidence from human post mortem, in vivo and animal model studies implicates the neuroimmune system and activated microglia in the pathology of amyotrophic lateral sclerosis. The study aim was to further evaluate in vivo neuroinflammation in individuals with amyotrophic lateral sclerosis using [C-11]-PBR28 positron emission tomography. Ten patients with amyotrophic lateral sclerosis (seven males, three females, 38-68 years) and ten age-and [C-11]-PBR28 binding affinity-matched healthy volunteers (six males, four females, 33-65 years) completed a positron emission tomography scan. Standardized uptake values were calculated from 60 to 90 min post-injection and normalized to whole brain mean. Voxel-wise analysis showed increased binding in the motor cortices and corticospinal tracts in patients with amyotrophic lateral sclerosis compared to healthy controls (p(FWE) < 0.05). Region of interest analysis revealed increased [C-11]-PBR28 binding in the precentral gyrus in patients (normalized standardized uptake value = 1.15) compared to controls (1.03, p < 0.05). In patients those values were positively correlated with upper motor neuron burden scores (r = 0.69, p < 0.05), and negatively correlated with the amyotrophic lateral sclerosis functional rating scale (r = -0.66, p < 0.05). Increased in vivo glial activation in motor cortices, that correlates with phenotype, complements previous histopathological reports. Further studies will determine the role of [C-11]-PBR28 as a marker of treatments that target neuroinflammation. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Zuercher, Nicole R.; Loggia, Marco L.; Chonde, Daniel B.; Izquierdo-Garcia, David; Catana, Ciprian; Rosen, Bruce R.; Hooker, Jacob M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging Dept Radiol, Charlestown, MA USA. [Lawson, Robert; Yasek, Julia E.; Cudkowicz, Merit E.] Harvard Univ, Sch Med, Dept Neurol, NCRI,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Akeju, Oluwaseun] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol, Boston, MA USA. RP Atassi, N (reprint author), Massachusetts Gen Hosp, Neurol Clin Res Inst, 165 Cambridge St,Suite 656, Boston, MA 02114 USA. EM hooker@nmr.mgh.harvard.edu; natassi@mgh.harvard.edu FU Harvard NeuroDiscovery Center; Muscular Dystrophy Association (MDA); American Academy of Neurology (AAN); Anne Young Fellowship; NINDS [1K23NS083715-01A1] FX The study was conducted at the A. A. Martinos Center for Biomedical Imaging and funded by a grant from the Harvard NeuroDiscovery Center. Dr. Atassi received fellowship grants from the Muscular Dystrophy Association (MDA), the American Academy of Neurology (AAN), the Anne Young Fellowship, and 1K23NS083715-01A1 grant from NINDS. NR 28 TC 27 Z9 28 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2015 VL 7 BP 409 EP 414 DI 10.1016/j.nicl.2015.01.009 PG 6 WC Neuroimaging SC Neurosciences & Neurology GA DI0GE UT WOS:000373172600045 PM 25685708 ER PT J AU Putcha, D Ross, RS Cronin-Golomb, A Janes, AC Stern, CE AF Putcha, Deepti Ross, Robert S. Cronin-Golomb, Alice Janes, Amy C. Stern, Chantal E. TI Altered intrinsic functional coupling between core neurocognitive networks in Parkinson's disease SO NEUROIMAGE-CLINICAL LA English DT Article DE Parkinson's disease; fMRI; Functional connectivity; DMN; SN; CEN ID DEFAULT-MODE NETWORK; RESTING-STATE; HUMAN BRAIN; CONNECTIVITY NETWORKS; BASAL GANGLIA; DYSFUNCTION; STRIATUM; ARCHITECTURE; SYMPTOMS; DEFICITS AB Parkinson's disease (PD) is largely attributed to disruptions in the nigrostriatal dopamine system. These neurodegenerative changes may also have a more global effect on intrinsic brain organization at the cortical level. Functional brain connectivity between neurocognitive systems related to cognitive processing is critical for effective neural communication, and is disrupted across neurological disorders. Three core neurocognitive networks have been established as playing a critical role in the pathophysiology of many neurological disorders: the default-mode network (DMN), the salience network (SN), and the central executive network (CEN). In healthy adults, DMN-CEN interactions are anti-correlated while SN-CEN interactions are strongly positively correlated even at rest, when individuals are not engaging in any task. These intrinsic between-network interactions at rest are necessary for efficient suppression of the DMN and activation of the CEN during a range of cognitive tasks. To identify whether these network interactions are disrupted in individuals with PD, we used resting state functional magnetic resonance imaging (rsfMRI) to compare between-network connectivity between 24 PD participants and 20 age-matched controls (MC). In comparison to the MC, individuals with PD showed significantly less SN-CEN coupling and greater DMN-CEN coupling during rest. Disease severity, an index of striatal dysfunction, was related to reduced functional coupling between the striatum and SN. These results demonstrate that individuals with PD have a dysfunctional pattern of interaction between core neurocognitive networks compared to what is found in healthy individuals, and that interaction between the SN and the striatum is even more profoundly disrupted in those with greater disease severity. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Putcha, Deepti; Ross, Robert S.; Cronin-Golomb, Alice; Stern, Chantal E.] Boston Univ, Dept Psychol & Brain Sci, Boston, MA 02115 USA. [Putcha, Deepti; Ross, Robert S.; Stern, Chantal E.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Ross, Robert S.] Univ New Hampshire, Dept Psychol, Durham, NH 03824 USA. [Janes, Amy C.] Harvard Univ, Sch Med, Dept Psychiat, McLean Imaging Ctr,McLean Hosp, Belmont, MA 02478 USA. RP Putcha, D (reprint author), Ctr Psychol & Brain Sci, 2 Cummington Mall,Rm 109, Boston, MA 02215 USA. EM dputcha@bu.edu RI Janes, Amy/A-5322-2013; OI Janes, Amy/0000-0002-3749-5006; Ross, Robert/0000-0002-3987-881X FU National Institute of Health [R01 NS067128]; National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health [P41EB015896]; NIH [S10RR022976, S10RR019933]; [K01DA029645] FX This work was supported by the National Institute of Health R01 NS067128. Scanning was carried out at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, which receives funding from P41EB015896, a Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health. This work also involved the use of instrumentation supported by the NIH Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program; specifically, grant number(s) S10RR022976 and S10RR019933. We also acknowledge salary funding for ACJ from grant number K01DA029645. NR 61 TC 11 Z9 12 U1 4 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2015 VL 7 BP 449 EP 455 DI 10.1016/j.nicl.2015.01.012 PG 7 WC Neuroimaging SC Neurosciences & Neurology GA DI0GE UT WOS:000373172600049 PM 25685711 ER PT J AU Kim, H Kim, J Loggia, ML Cahalan, C Garcia, RG Vangel, MG Wasan, AD Edwards, RR Napadow, V AF Kim, Hyungjun Kim, Jieun Loggia, Marco L. Cahalan, Christine Garcia, Ronald G. Vangel, Mark G. Wasan, Ajay D. Edwards, Robert R. Napadow, Vitaly TI Fibromyalgia is characterized by altered frontal and cerebellar structural covariance brain networks SO NEUROIMAGE-CLINICAL LA English DT Article DE Fibromyalgia; Pain; Network; Tractography; Cerebellum ID VOXEL-BASED MORPHOMETRY; CHRONIC PAIN; FUNCTIONAL CONNECTIVITY; WHITE-MATTER; ANATOMICAL PARCELLATION; CORTICAL THICKNESS; DIFFUSION-TENSOR; CORTEX; MRI; INTENSITY AB Altered brain morphometry has been widely acknowledged in chronic pain, and recent studies have implicated altered network dynamics, as opposed to properties of individual brain regions, in supporting persistent pain. Structural covariance analysis determines the inter-regional association in morphological metrics, such as gray matter volume, and such structural associations may be altered in chronic pain. In this study, voxel-based morphometry structural covariance networks were compared between fibromyalgia patients (N=42) and age-and sex-matched pain-free adults (N=63). We investigated network topology using spectral partitioning, which can delineate local network submodules with consistent structural covariance. We also explored white matter connectivity between regions comprising these submodules and evaluated the association between probabilistic white matter tractography and pain-relevant clinical metrics. Our structural covariance network analysis noted more connections within the cerebellum for fibromyalgia patients, and more connections in the frontal lobe for healthy controls. For fibromyalgia patients, spectral partitioning identified a distinct submodule with cerebellar connections to medial prefrontal and temporal and right inferior parietal lobes, whose gray matter volume was associated with the severity of depression in these patients. Volume for a submodule encompassing lateral orbitofrontal, inferior frontal, postcentral, lateral temporal, and insular cortices was correlated with evoked pain sensitivity. Additionally, the number of white matter fibers between specific submodule regions was also associated with measures of evoked pain sensitivity and clinical pain interference. Hence, altered gray and white matter morphometry in cerebellar and frontal cortical regions may contribute to, or result from, pain-relevant dysfunction in chronic pain patients. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Kim, Hyungjun; Kim, Jieun; Loggia, Marco L.; Garcia, Ronald G.; Vangel, Mark G.; Napadow, Vitaly] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Kim, Hyungjun; Kim, Jieun] Korea Inst Oriental Med, Div Med Res, Daejeon 305811, South Korea. [Cahalan, Christine; Edwards, Robert R.; Napadow, Vitaly] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Chestnut Hill, MA 02467 USA. [Garcia, Ronald G.] Univ Santander, Sch Med, Bucaramanga, Colombia. [Wasan, Ajay D.] Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA 15261 USA. [Wasan, Ajay D.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15261 USA. [Napadow, Vitaly] Kyung Hee Univ, Coll Elect & Informat, Dept Biomed Engn, Yongin 449701, South Korea. RP Kim, H (reprint author), Martinos Ctr Biomed Imaging, Bldg 149,Suite 2301, Charlestown, MA 02129 USA. EM hengjun@nmr.mgh.harvard.edu OI Garcia, Ronald Gerardo/0000-0002-8325-9944 FU National Center for Complementary and Alternative Medicine [P01-AT006663, R01-AT007550, R01-AR064367]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [R21-AR057920]; Korean Institute of Oriental Medicine [K15050]; [1S10RR023043] FX This research was supported by National Center for Complementary and Alternative Medicine (P01-AT006663, R01-AT007550, R01-AR064367), National Institute of Arthritis and Musculoskeletal and Skin Diseases (R21-AR057920) and Korean Institute of Oriental Medicine (K15050). This research was made possible by the resources provided by Shared Instrumentation Grant (1S10RR023043). NR 72 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2015 VL 7 BP 667 EP 677 DI 10.1016/j.nicl.2015.02.022 PG 11 WC Neuroimaging SC Neurosciences & Neurology GA DI0GE UT WOS:000373172600072 PM 25844321 ER PT J AU Shinohara, RT Sweeney, EM Goldsmith, J Shiee, N Mateen, FJ Calabresi, PA Jarso, S Pham, DL Reich, DS Crainiceanu, CM AF Shinohara, Russell T. Sweeney, Elizabeth M. Goldsmith, Jeff Shiee, Navid Mateen, Farrah J. Calabresi, Peter A. Jarso, Samson Pham, Dzung L. Reich, Daniel S. Crainiceanu, Ciprian M. CA Australian Imaging Biomarkers Alzheimer's Dis Neuroimaging TI Statistical normalization techniques for magnetic resonance imaging (vol 6, pg 9, 2014) SO NEUROIMAGE-CLINICAL LA English DT Correction C1 [Shinohara, Russell T.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Sweeney, Elizabeth M.; Reich, Daniel S.] NINDS, Translat Neurol Unit, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [Sweeney, Elizabeth M.; Reich, Daniel S.; Crainiceanu, Ciprian M.] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. [Goldsmith, Jeff] Columbia Univ, Dept Biostat, New York, NY 10032 USA. [Shiee, Navid; Pham, Dzung L.] Henry M Jackson Fdn, Ctr Neurosci & Regenerat Med, Bethesda, MD 20892 USA. [Mateen, Farrah J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Mateen, Farrah J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Calabresi, Peter A.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA. [Jarso, Samson; Reich, Daniel S.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21287 USA. RP Shinohara, RT (reprint author), Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, 210 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM rshi@upenn.edu RI Reich, Daniel/E-5701-2010 OI Reich, Daniel/0000-0002-2628-4334 NR 1 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2015 VL 7 BP 848 EP 848 DI 10.1016/j.nicl.2015.02.011 PG 1 WC Neuroimaging SC Neurosciences & Neurology GA DI0GE UT WOS:000373172600093 PM 26082894 ER PT J AU Val-Laillet, D Aarts, E Weber, B Ferrari, M Quaresima, V Stoeckel, LE Alonso-Alonso, M Audette, M Malbert, CH Stice, E AF Val-Laillet, D. Aarts, E. Weber, B. Ferrari, M. Quaresima, V. Stoeckel, L. E. Alonso-Alonso, M. Audette, M. Malbert, C. H. Stice, E. TI Neuroimaging and neuromodulation approaches to study eating behavior and prevent and treat eating disorders and obesity SO NEUROIMAGE-CLINICAL LA English DT Review DE Brain; Neuroimaging; Neuromodulation; Obesity; Eating disorders; Human ID DEEP BRAIN-STIMULATION; NEAR-INFRARED SPECTROSCOPY; TRANSCRANIAL MAGNETIC STIMULATION; VAGUS NERVE-STIMULATION; REAL-TIME FMRI; GASTRIC-BYPASS-SURGERY; BODY-MASS INDEX; DOPAMINE D2 RECEPTOR; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; OBSESSIVE-COMPULSIVE DISORDER AB Functional, molecular and genetic neuroimaging has highlighted the existence of brain anomalies and neural vulnerability factors related to obesity and eating disorders such as binge eating or anorexia nervosa. In particular, decreased basal metabolism in the prefrontal cortex and striatum as well as dopaminergic alterations have been described in obese subjects, in parallel with increased activation of reward brain areas in response to palatable food cues. Elevated reward region responsivity may trigger food craving and predict future weight gain. This opens the way to prevention studies using functional and molecular neuroimaging to perform early diagnostics and to phenotype subjects at risk by exploring different neurobehavioral dimensions of the food choices and motivation processes. In the first part of this review, advantages and limitations of neuroimaging techniques, such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), pharmacogenetic fMRI and functional near-infrared spectroscopy (fNIRS) will be discussed in the context of recent work dealing with eating behavior, with a particular focus on obesity. In the second part of the review, non-invasive strategies to modulate food-related brain processes and functions will be presented. At the leading edge of non-invasive brain-based technologies is real-time fMRI (rtfMRI) neurofeedback, which is a powerful tool to better understand the complexity of human brain-behavior relationships. rtfMRI, alone or when combined with other techniques and tools such as EEG and cognitive therapy, could be used to alter neural plasticity and learned behavior to optimize and/or restore healthy cognition and eating behavior. Other promising non-invasive neuromodulation approaches being explored are repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS). Converging evidence points at the value of these non-invasive neuromodulation strategies to study basic mechanisms underlying eating behavior and to treat its disorders. Both of these approaches will be compared in light of recent work in this field, while addressing technical and practical questions. The third part of this review will be dedicated to invasive neuromodulation strategies, such as vagus nerve stimulation (VNS) and deep brain stimulation (DBS). In combination with neuroimaging approaches, these techniques are promising experimental tools to unravel the intricate relationships between homeostatic and hedonic brain circuits. Their potential as additional therapeutic tools to combat pharmacorefractory morbid obesity or acute eating disorders will be discussed, in terms of technical challenges, applicability and ethics. In a general discussion, we will put the brain at the core of fundamental research, prevention and therapy in the context of obesity and eating disorders. First, we will discuss the possibility to identify new biological markers of brain functions. Second, we will highlight the potential of neuroimaging and neuromodulation in individualized medicine. Third, we will introduce the ethical questions that are concomitant to the emergence of new neuromodulation therapies. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Val-Laillet, D.] INRA, UR1341, ADNC, F-35650 Lyon, France. [Aarts, E.] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands. [Weber, B.] Univ Hosp Bonn, Dept Epileptol, Bonn, Germany. [Ferrari, M.; Quaresima, V.] Univ Aquila, Dept Life Hlth & Environm Sci, I-67100 Laquila, Italy. [Stoeckel, L. E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Alonso-Alonso, M.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Cambridge, MA 02138 USA. [Audette, M.] Old Dominion Univ, Norfolk, VA 23529 USA. [Malbert, C. H.] INRA, Ani Scans US1395, F-35650 Lyon, France. [Stice, E.] Oregon Res Inst, Eugene, OR USA. RP Val-Laillet, D (reprint author), INRA, UR1341, ADNC, F-35650 Lyon, France. EM david.val-laillet@rennes.inra.fr RI Aarts, Esther/J-2254-2012; OI FERRARI, Marco/0000-0002-3041-2917; Aarts, Esther/0000-0001-6360-6200; Malbert, Charles-Henri/0000-0002-0665-4545; quaresima, valentina/0000-0001-9884-0304 FU INRA; Brittany Region (France) in the context of the FP7 European Program; Boston Nutrition and Obesity Research Center (BNORC) [5P30 DK046200]; Nutrition Obesity Research Center at Harvard (NORCH) [P30 DK040561]; Roadmap Supplement [R1MH64560A, R01 DK080760, R01 DK092468]; VENI grant of The Netherlands Organization for Scientific Research (NWO); AXA Research Fund fellowship; National Institutes of Health [K23DA032612, R21DA030523]; Norman E. Zinberg Fellowship in Addiction Psychiatry at Harvard Medical School; Charles A. King Trust; McGovern Institute Neurotechnology Program FX This reviewtopic was proposed by the Nova Brain International Consortium that was created in 2012 with the aim to promote innovative research to explore the relationships between brain functions and eating behaviors (Coordinator: David Val-Laillet, INRA, France). The founding members of the Nova Brain Consortium were: Institut National de la Recherche Agronomique (INRA, France), INRA Transfert S A. (France), Wageningen University (The Netherlands), Institute of Agriculture and Food Research and Technology (IRTA, Spain), University Hospital Bonn (Germany), Institut Europeen d' Administration des Affaires (INSEAD, France), University of Surrey (UK), Radboud University Nijmegen, The Netherlands, Noldus Information Technology BV (The Netherlands), University of Queensland (Australia), Oregon Research Institute (USA), Pennington Biomedical Research Centre (USA), Centre National de La Recherche Scientifique (CNRS, France), Old Dominion University (USA), Stichting Dienst Landbouwkundig Onderzoek - Food & Biobased Research, The Netherlands, Aix-Marseille University (France), i3B Innovations BV (The Netherlands), Jozef Stefan Institute (Slovenia), University of Bologna (Italy). The preparation and initial meetings of the NovaBrain Consortium were co-funded by INRA and the Brittany Region (France) in the context of the FP7 European Program. Dr. Alonso-Alonso is a recipient of grants from the Boston Nutrition and Obesity Research Center (BNORC), 5P30 DK046200, and the Nutrition Obesity Research Center at Harvard (NORCH), P30 DK040561. Dr. Eric Stice benefited from the following grants for the research mentioned herein: Roadmap Supplement R1MH64560A; R01 DK080760; and R01 DK092468. Bernd Weber was supported by a Heisenberg Grant of the German Research Council (DFG; We 4427/3-1). Dr. Esther Aarts was supported by a VENI grant of The Netherlands Organization for Scientific Research (NWO) (016.135.023) and an AXA Research Fund fellowship (Ref: 2011). Luke Stoeckel received a financial support from the National Institutes of Health (K23DA032612; R21DA030523), the Norman E. Zinberg Fellowship in Addiction Psychiatry at Harvard Medical School, the Charles A. King Trust, the McGovern Institute Neurotechnology Program, and private funds to the Massachusetts General Hospital Department of Psychiatry. Some research presented in this paper was carried out in part at the Athinoula A. Martinos Center for Biomedical Imaging at the McGovern Institute for Brain Research at the Massachusetts Institute of Technology. All the authors state that they have no conflict of interests related to this manuscript. NR 397 TC 45 Z9 45 U1 29 U2 90 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2015 VL 8 BP 1 EP 31 DI 10.1016/j.nicl.2015.03.016 PG 31 WC Neuroimaging SC Neurosciences & Neurology GA DI0LE UT WOS:000373187100001 PM 26110109 ER PT J AU Hayes, JP Miller, DR Lafleche, G Salat, DH Verfaellie, M AF Hayes, Jasmeet P. Miller, Danielle R. Lafleche, Ginette Salat, David H. Verfaellie, Mieke TI The nature of white matter abnormalities in blast-related mild traumatic brain injury SO NEUROIMAGE-CLINICAL LA English DT Article DE Fractional anisotropy; PTSD; Diffusion tensor imaging; OEF/OIF; Loss of consciousness ID POSTTRAUMATIC-STRESS-DISORDER; OEF/OIF VETERANS; IRAQI FREEDOM; SELF-REPORT; PTSD; CONCUSSION; INTEGRITY; SYMPTOMS; DEFICITS; AFGHANISTAN AB Blast-related traumatic brain injury (TBI) has been a common injury among returning troops due to the widespread use of improvised explosive devices in the Iraq and Afghanistan Wars. As most of the TBIs sustained are in the mild range, brain changes may not be detected by standard clinical imaging techniques such as CT. Furthermore, the functional significance of these types of injuries is currently being debated. However, accumulating evidence suggests that diffusion tensor imaging (DTI) is sensitive to subtle white matter abnormalities and may be especially useful in detecting mild TBI (mTBI). The primary aim of this study was to use DTI to characterize the nature of white matter abnormalities following blast-related mTBI, and in particular, examine the extent to which mTBI-related white matter abnormalities are region-specific or spatially heterogeneous. In addition, we examined whether mTBI with loss of consciousness (LOC) was associated with more extensive white matter abnormality than mTBI without LOC, as well as the potential moderating effect of number of blast exposures. A second aim was to examine the relationship between white matter integrity and neurocognitive function. Finally, a third aim was to examine the contribution of PTSD symptom severity to observed white matter alterations. One hundred fourteen OEF/OIF veterans underwent DTI and neuropsychological examination and were divided into three groups including a control group, blast-related mTBI without LOC (mTBI-LOC) group, and blast-related mTBI with LOC (mTBI + LOC) group. Hierarchical regression models were used to examine the extent to which mTBI and PTSD predicted white matter abnormalities using two approaches: 1) a region-specific analysis and 2) a measure of spatial heterogeneity. Neurocognitive composite scores were calculated for executive functions, attention, memory, and psychomotor speed. Results showed that blast-related mTBI + LOC was associated with greater odds of having spatially heterogeneous white matter abnormalities. Region-specific reduction in fractional anisotropy (FA) in the left retrolenticular part of the internal capsule was observed in the mTBI + LOC group as the number of blast exposures increased. A mediation analysis revealed that mTBI + LOC indirectly influenced verbal memory performance through its effect on white matter integrity. PTSD was not associated with spatially heterogeneous white matter abnormalities. However, there was a suggestion that at higher levels of PTSD symptom severity, LOC was associated with reduced FA in the left retrolenticular part of the internal capsule. These results support postmortem reports of diffuse axonal injury following mTBI and suggest that injuries with LOC involvement may be particularly detrimental to white matter integrity. Furthermore, these results suggest that LOC-associatedwhitematter abnormalities in turn influence neurocognitive function. Published by Elsevier Inc. C1 [Hayes, Jasmeet P.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Hayes, Jasmeet P.; Lafleche, Ginette; Verfaellie, Mieke] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Hayes, Jasmeet P.; Salat, David H.] VA Boston Healthcare Syst, Neuroimaging Res Vet Ctr, Boston, MA 02130 USA. [Miller, Danielle R.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Miller, Danielle R.; Lafleche, Ginette; Verfaellie, Mieke] VA Boston Healthcare Syst, Memory Disorders Res Ctr, Boston, MA 02130 USA. [Salat, David H.] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02115 USA. [Salat, David H.] Harvard Univ, Sch Med, Boston, MA USA. RP Hayes, JP (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B2, 150 S Huntington Ave, Boston, MA 02130 USA. EM jphayes@bu.edu OI Miller, Danielle R./0000-0002-0141-5887 FU VA Merit Review [822-MR-18176]; NIH grant [K23MH084013]; National Center for PTSD; VA Clinical Science Research and Development Service FX This work was supported by VA Merit Review 822-MR-18176 (awarded to M.V.), NIH grant K23MH084013 (awarded to J.P.H.), the National Center for PTSD, and the VA Clinical Science Research and Development Service. NR 45 TC 10 Z9 11 U1 3 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2015 VL 8 BP 148 EP 156 DI 10.1016/j.nicl.2015.04.001 PG 9 WC Neuroimaging SC Neurosciences & Neurology GA DI0LE UT WOS:000373187100016 PM 26106539 ER PT J AU Barbeau, EB Lewis, JD Doyon, J Benali, H Zeffiro, TA Mottron, L AF Barbeau, Elise B. Lewis, John D. Doyon, Julien Benali, Habib Zeffiro, Thomas A. Mottron, Laurent TI A greater involvement of posterior brain areas in interhemispheric transfer in autism: fMRI, DWI and behavioral evidences SO NEUROIMAGE-CLINICAL LA English DT Article DE Corpus callosum; Poffenberger; Purdue; Visuo-motor integration; Autism; Cortical reorganization ID HIGH-FUNCTIONING AUTISM; SIMPLE REACTION-TIMES; CORPUS-CALLOSUM; SPECTRUM DISORDERS; WHITE-MATTER; VISUOMOTOR INFORMATION; CORTICAL UNDERCONNECTIVITY; SENTENCE COMPREHENSION; MULTIPLE-SCLEROSIS; YOUNG-ADULTS AB A small corpus callosum (CC) is one of the most replicated neurobiological findings in autism spectrum (AS). However, its effect on interhemispheric (IH) communication is unknown. We combined structural (CC area and DWI), functional (task-related fMRI activation and connectivity analyses) as well as behavioral (Poffenberger and Purdue tasks) measures to investigate IH integration in adult AS individuals of typical intelligence. Despite similar behavioral IH transfer time and performances in bimanual tasks, the CC sub-regions connecting frontal and parietal cortical areas were smaller in AS than in non-AS individuals, while those connecting visual regions were similar. The activation of visual areas was lower in AS than in non-AS individuals during the presentation of visual stimuli. Behavioral IH performances were related to the properties of CC subregions connecting motor areas in non-AS individuals, but to the properties of posterior CC regions in AS individuals. Furthermore, there was greater functional connectivity between visual areas in the AS than in the non-AS group. Levels of connectivity were also stronger in visual than in motor regions in the autistic subjects, while the opposite was true for the non-autistic group. Thus, visual IH transfer plays an important role in visuo-motor tasks in AS individuals. These findings extend the well established enhanced role of perception in autistic cognition to visuo-motor IH information transfer. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Barbeau, Elise B.; Mottron, Laurent] Univ Montreal CETEDUM, Ctr Excellence Troubles Envahissants Dev, Montreal, PQ, Canada. [Barbeau, Elise B.; Mottron, Laurent] Inst Univ Sante Mentale Montreal, Ctr Rech, Montreal, PQ, Canada. [Barbeau, Elise B.; Mottron, Laurent] Univ Montreal, Dept Psychiat, Montreal, PQ H3C 3J7, Canada. [Lewis, John D.] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. [Doyon, Julien] Univ Montreal, Dept Psychol, Montreal, PQ H3C 3J7, Canada. [Doyon, Julien] UNF, Montreal, PQ, Canada. [Benali, Habib] Fac Med Pierre & Marie Curie Pitie Salpetriere, U678, Lab Imagerie Fonct, Paris, France. [Zeffiro, Thomas A.] Massachusetts Gen Hosp, Neural Syst Grp, Psychiat, Charlestown, MA USA. RP Mottron, L (reprint author), Hop Riviere des Prairies, 7070 Blvd Perras, Montreal, PQ H1E 1A4, Canada. EM laurent.mottron@gmail.com FU Canadian Institutes of Health Research (CIHR) [MOP-84243]; Calcul Quebec; Compute Canada FX This work was supported by an operating grant from the Canadian Institutes of Health Research (CIHR, No. MOP-84243) to L. Mottron, and scholarship from the CIHR to E.B. Barbeau. This research was also enabled in part by support provided by Calcul Quebec (www.calculquebec.ca) and Compute Canada (www.computecanada.ca). The authors want to thank the participants for their invaluable contribution to this project. The authors report no potential conflicts of interest. NR 100 TC 3 Z9 3 U1 5 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2015 VL 8 BP 267 EP 280 DI 10.1016/j.nicl.2015.04.019 PG 14 WC Neuroimaging SC Neurosciences & Neurology GA DI0LE UT WOS:000373187100029 PM 26106551 ER PT J AU Fling, BW Dutta, GG Horak, FB AF Fling, Brett W. Dutta, Geetanjali Gera Horak, Fay B. TI Functional connectivity underlying postural motor adaptation in people with multiple sclerosis SO NEUROIMAGE-CLINICAL LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; GRAY-MATTER ATROPHY; CEREBELLAR CORTEX; VIRTUAL-REALITY; BASAL GANGLIA; LESION LOAD; BRAIN; MECHANISMS; PLASTICITY; ADULTS AB A well-characterized neural network is associated with motor learning, involving several brain regions known to have functional and structural deficits in persons with multiple sclerosis (PwMS). However, it is not known how MS affects postural motor learning or the neural networks involved. The aim of this study was to gain a better understanding of the neural networks underlying adaptation of postural responses within PwMS. Participants stood on a hydraulically driven, servo-controlled platform that translated horizontally forward and backward in a continuous sinusoidal pattern across multiple trials over two consecutive days. Our results show similar postural adaptation between PwMS and age-matched control participants despite overall deficits in postural motor control in PwMS. Moreover, PwMS demonstrated better retention the following day. PwMS had significantly reduced functional connectivity within both the cortico-cerebellar and cortico-striatal motor loops; neural networks that subserve implicit motor learning. In PwMS, greater connectivity strength within the cortico-cerebellar circuit was strongly related to better baseline postural control, but not to postural adaptation as it was in control participants. Further, anti-correlated cortico-striatal connectivity within the right hemisphere was related to improved postural adaptation in both groups. Taken together with previous studies showing a reduced reliance on cerebellar-and proprioceptive-related feedback control in PwMS, we suggest that PwMS may rely on cortico-striatal circuitry to a greater extent than cortico-cerebellar circuitry for the acquisition and retention of motor skills. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Fling, Brett W.; Dutta, Geetanjali Gera; Horak, Fay B.] Oregon Hlth & Sci Univ, Sch Med, Dept Neurol, Portland, OR 97239 USA. [Fling, Brett W.; Horak, Fay B.] Portland VA Med Ctr, Portland, OR 97239 USA. RP Fling, BW (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM fling@ohsu.edu FU National Multiple Sclerosis Society [RG 5273A1/T, FG 2058-A-1, MB0011]; Medical Research Foundation of Oregon; N.L. Tartar Research Fund FX We thank the volunteers for participating in this study. We are also grateful to Heather Schlueter for assistance in participant recruitment and data collection. This work was principally supported by grants from the National Multiple Sclerosis Society (BWF: RG 5273A1/T, GGD: FG 2058-A-1 and FBH: MB0011). Additional support was provided by the Medical Research Foundation of Oregon (BWF & GGD) and the N.L. Tartar Research Fund (BWF). The authors declare no competing financial interests. NR 73 TC 2 Z9 2 U1 2 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2015 VL 8 BP 281 EP 289 DI 10.1016/j.nicl.2015.04.023 PG 9 WC Neuroimaging SC Neurosciences & Neurology GA DI0LE UT WOS:000373187100030 PM 26106552 ER PT J AU Chai, XQJ Hirshfeld-Becker, D Biederman, J Uchida, M Doehrmann, O Leonard, JA Salvatore, J Kenworthy, T Brown, A Kagan, E de los Angeles, C Whitfield-Gabrieli, S Gabrieli, JDE AF Chai, Xiaoqian J. Hirshfeld-Becker, Dina Biederman, Joseph Uchida, Mai Doehrmann, Oliver Leonard, Julia A. Salvatore, John Kenworthy, Tara Brown, Ariel Kagan, Elana de los Angeles, Carlo Whitfield-Gabrieli, Susan Gabrieli, John D. E. TI Functional and structural brain correlates of risk for major depression in children with familial depression SO NEUROIMAGE-CLINICAL LA English DT Article DE fMRI; Major depression; Children; Familial risk; Emotional faces; Amygdala volume ID HAPPY FACIAL EXPRESSIONS; NEURAL RESPONSE; HUMAN AMYGDALA; EMOTIONAL FACES; PANIC DISORDER; ANTIDEPRESSANT TREATMENT; ATTENTIONAL BIASES; ACTIVATION; FMRI; ADOLESCENTS AB Despite growing evidence for atypical amygdala function and structure in major depression, it remains uncertain as to whether these brain differences reflect the clinical state of depression or neurobiological traits that predispose individuals to major depression. We examined function and structure of the amygdala and associated areas in a group of unaffected children of depressed parents (at-risk group) and a group of children of parents without a history of major depression (control group). Compared to the control group, the at-risk group showed increased activation to fearful relative to neutral facial expressions in the amygdala and multiple cortical regions, and decreased activation to happy relative to neutral facial expressions in the anterior cingulate cortex and supramarginal gyrus. At-risk children also exhibited reduced amygdala volume. The extensive hyperactivation to negative facial expressions and hypoactivation to positive facial expressions in at-risk children are consistent with behavioral evidence that risk for major depression involves a bias to attend to negative information. These functional and structural brain differences between at-risk children and controls suggest that there are trait neurobiological underpinnings of risk for major depression. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Chai, Xiaoqian J.; Doehrmann, Oliver; Leonard, Julia A.; Salvatore, John; de los Angeles, Carlo; Whitfield-Gabrieli, Susan; Gabrieli, John D. E.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Chai, Xiaoqian J.; Doehrmann, Oliver; Leonard, Julia A.; Salvatore, John; de los Angeles, Carlo; Whitfield-Gabrieli, Susan; Gabrieli, John D. E.] MIT, McGovern Inst Brain Res, Poitras Ctr Affect Disorders Res, Cambridge, MA 02139 USA. [Hirshfeld-Becker, Dina; Biederman, Joseph; Uchida, Mai; Kenworthy, Tara; Brown, Ariel; Kagan, Elana] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Biederman, Joseph; Uchida, Mai; Kenworthy, Tara; Brown, Ariel; Kagan, Elana] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Gabrieli, John D. E.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. RP Chai, XQJ (reprint author), 43 Vassar St,46 5081,Bldg 46, Cambridge, MA 02139 USA. EM xiaoqian@mit.edu FU National Institute of Health (NIH) [R01 HD036317, R01 MH050657]; Tommy Fuss Fund; Poitras Center for Affective Disorders Research; MGH Pediatric Psychopharmacology Council Fund; NIH [R01 MH636833, R01 MH/CHD076923, R01 MH47077] FX We wish to thank Gretchen Reynolds, Daniel O'Young and Jiahe Zhang for their help with collecting imaging data. This research was carried out at the Athinoula A. Martinos Imaging Center at the McGovern Institute for Brain Research at the Massachusetts Institute of Technology and Massachusetts general hospital. The study was supported by the National Institute of Health (NIH) grants to JB (R01 HD036317; R01 MH050657), the Tommy Fuss Fund, the Poitras Center for Affective Disorders Research, and the MGH Pediatric Psychopharmacology Council Fund. The original participant recruitment was supported by NIH grants to DHB (R01 MH636833; R01 MH/CHD076923), and R01 MH47077 (PI: Rosenbaum). The funding sources had no involvement in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. NR 57 TC 2 Z9 2 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2015 VL 8 BP 398 EP 407 DI 10.1016/j.nicl.2015.05.004 PG 10 WC Neuroimaging SC Neurosciences & Neurology GA DI0LE UT WOS:000373187100043 PM 26106565 ER PT J AU Hove, MJ Zeffiro, TA Biederman, J Li, Z Schmahmann, J Valera, EM AF Hove, Michael J. Zeffiro, Thomas A. Biederman, Joseph Li, Zhi Schmahmann, Jeremy Valera, Eve M. TI Postural sway and regional cerebellar volume in adults with attention-deficit/hyperactivity disorder SO NEUROIMAGE-CLINICAL LA English DT Article DE Attention-deficit hyperactivity disorder (ADHD); Postural balance; Cerebellum ID DEFICIT HYPERACTIVITY DISORDER; VOXEL-BASED MORPHOMETRY; FUNCTIONAL CONNECTIVITY; CHILDREN; ORGANIZATION; ADHD; ABNORMALITIES; METAANALYSIS; PERFORMANCE; TOPOGRAPHY AB Objective: Motor abnormalities, including impaired balance and increased postural sway, are commonly reported in children with ADHD, but have yet to be investigated in adults with ADHD. Furthermore, although these abnormalities are thought to stem from cerebellar deficits, evidence for an association between the cerebellum and these motor deficits has yet to be provided for either adults or children with ADHD. Method: In this study, we measured postural sway in adults with ADHD and controls, examining the relationship between sway and regional cerebellar gray matter volume. Thirty-two ADHD and 28 control participants completed various standing-posture tasks on a Wii balance board. Results: Postural sway was significantly higher for the ADHD group compared to the healthy controls. Higher sway was positively associated with regional gray matter volume in the right posterior cerebellum (lobule VIII/IX). Conclusion: These findings show that sway abnormalities commonly reported in children with ADHD are also present in adults, and for the first time show a relationship between postural control atypicalities and the cerebellum in this group. Our findings extend the literature on motor abnormalities in ADHD and contribute to our knowledge of their neural substrate. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Hove, Michael J.; Biederman, Joseph; Li, Zhi; Valera, Eve M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Room 2660,149 13th St, Charlestown, MA 02129 USA. [Zeffiro, Thomas A.] Neurometrika, Potomac, MD 20854 USA. [Schmahmann, Jeremy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. RP Valera, EM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Room 2660,149 13th St, Charlestown, MA 02129 USA. EM eve_valera@hms.harvard.edu FU National Institutes of Health [T32 MH16259, R01 HD067744-01A1]; NCRR [P41RR14075]; National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health [P41EB015896]; NIH [1S10RR023043, 1S10RR023401] FX We thank Dr. Vladimir Ivkovic for his insightful and helpful comments on versions of this manuscript. This work was supported by grants from the National Institutes of Health T32 MH16259 (to MJH) and R01 HD067744-01A1 (to EMV) and NCRR P41RR14075. This research was carried out in whole or 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, P41EB015896, a P41 Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health. This work also involved the use of instrumentation supported by the NIH Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program; specifically, grant numbers 1S10RR023043 and 1S10RR023401. NR 54 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2015 VL 8 BP 422 EP 428 DI 10.1016/j.nicl.2015.05.005 PG 7 WC Neuroimaging SC Neurosciences & Neurology GA DI0LE UT WOS:000373187100045 PM 26106567 ER PT J AU Rieckmann, A Gomperts, SN Johnson, KA Growdon, JH Van Dijk, KRA AF Rieckmann, A. Gomperts, S. N. Johnson, K. A. Growdon, J. H. Van Dijk, K. R. A. TI Putamen-midbrain functional connectivity is related to striatal dopamine transporter availability in patients with Lewy body diseases SO NEUROIMAGE-CLINICAL LA English DT Article DE Functional connectivity; fMRI; PET; Dopamine transporter; Lewy body diseases ID PARKINSONS-DISEASE; RESTING-STATE; SUBSTANTIA-NIGRA; BRAIN; PET; DIAGNOSIS; DEMENTIA; MOTION; VOLUME; OPTIMIZATION AB Prior work has shown that functional connectivity between the midbrain and putamen is altered in patients with impairments in the dopamine system. This study examines whether individual differences in midbrain-striatal connectivity are proportional to the integrity of the dopamine system in patients with nigrostriatal dopamine loss (Parkinson's disease and dementia with Lewy bodies). We assessed functional connectivity of the putamen during resting state fMRI and dopamine transporter (DAT) availability in the striatum using 11C-Altropane PET in twenty patients. In line with the hypothesis that functional connectivity between the midbrain and the putamen reflects the integrity of the dopaminergic neurotransmitter system, putamen-midbrain functional connectivity was significantly correlated with striatal DAT availability even after stringent control for effects of head motion. DAT availability did not relate to functional connectivity between the caudate and thalamus/prefrontal areas. As such, resting state functional connectivity in the midbrain-striatal pathway may provide a useful indicator of underlying pathology in patients with nigrostriatal dopamine loss. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Rieckmann, A.; Van Dijk, K. R. A.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Rieckmann, A.] Umea Univ, Dept Radiat Sci, Diagnost Radiol, Umea, Sweden. [Gomperts, S. N.] MassGen Inst Neurodegenerat Dis, Boston, MA 02129 USA. [Gomperts, S. N.; Johnson, K. A.; Growdon, J. H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Johnson, K. A.] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Van Dijk, K. R. A.] Harvard Univ, Dept Psychol, Ctr Brain Sci, Cambridge, MA 02138 USA. RP Van Dijk, KRA (reprint author), Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, 149 13th St, Charlestown, MA 02129 USA. EM kvandijk@nmr.mgh.harvard.edu RI Van Dijk, Koene/G-3317-2012 OI Van Dijk, Koene/0000-0001-6137-4282 FU Michael J. Fox Foundation; National Alzheimer's Coordinating Center Collaborative Project [5 U01 AG016976-11]; National Institute of Neurological Disorders and Stroke [R21NS090243-01]; National Institute on Aging [P50 AG005134-32]; National Institute of Neurological Disorders and Stroke; National Institute on Aging; Alzheimer's Disease Association; Harvard Center for Neurodegeneration and Repair Pilot grant; Marie Curie International Outgoing Fellowship from the European Commission; National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health [P41EB015896]; National Institutes of Health [S10RR023401, S10RR019307, S10RR019254, S10RR023043] FX Data from cognitively normal older adults were collected in collaboration with contributors to the Harvard Aging Brain Study (http://www.martinos.org/harvardagingbrain/Acknowledgements.html); in particular we thank Randy Buckner, Trey Hedden and Reisa Sperling for providing the research funding and data for the healthy control group. The Massachusetts General Hospital Molecular Imaging PET Core provided assistance with PET Imaging. We thank Alex Becker, Marta Marquie, and Aaron Schultz for assistance with data analysis. This research was supported by The Michael J. Fox Foundation (to SNG and JHG), National Alzheimer's Coordinating Center Collaborative Project 5 U01 AG016976-11 (to SNG, KAJ, and JHG), the National Institute of Neurological Disorders and Stroke R21NS090243-01 (to SNG, JHG, and KAJ), the National Institute on Aging P50 AG005134-32, (to JHG), National Institute of Neurological Disorders and Stroke (to KAJ), the National Institute on Aging (to KAJ), the Alzheimer's Disease Association (to KAJ), and the Harvard Center for Neurodegeneration and Repair Pilot grant (to SNG). AR was supported by a Marie Curie International Outgoing Fellowship from the European Commission. This research was carried out in whole or 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, P41EB015896, a P41 Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health. This work also involved the use of instrumentation supported by the National Institutes of Health Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program (grant numbers S10RR023401, S10RR019307, S10RR019254, S10RR023043). The authors declare no competing financial interests. NR 44 TC 3 Z9 3 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2015 VL 8 BP 554 EP 559 DI 10.1016/j.nicl.2015.06.001 PG 6 WC Neuroimaging SC Neurosciences & Neurology GA DI0LE UT WOS:000373187100059 PM 26137443 ER PT J AU Chua, AS Egorova, S Anderson, MC Polgar-Turcsanyi, M Chitnis, T Weiner, HL Guttmann, CRG Bakshi, R Healy, BC AF Chua, Alicia S. Egorova, Svetlana Anderson, Mark C. Polgar-Turcsanyi, Mariann Chitnis, Tanuja Weiner, Howard L. Guttmann, Charles R. G. Bakshi, Rohit Healy, Brian C. TI Handling changes in MRI acquisition parameters in modeling whole brain lesion volume and atrophy data in multiple sclerosis subjects: Comparison of linear mixed-effect models SO NEUROIMAGE-CLINICAL LA English DT Article DE Multiple sclerosis; MRI; Brain atrophy; T2 lesion; Mixed-effect models ID QUANTITATIVE-ANALYSIS; WHITE-MATTER; QUANTIFICATION; DISEASE; SCALE; EDSS AB Magnetic resonance imaging (MRI) of the brain provides important outcome measures in the longitudinal evaluation of disease activity and progression in MS subjects. Two common measures derived from brain MRI scans are the brain parenchymal fraction (BPF) and T2 hyperintense lesion volume(T2LV), and these measures are routinely assessed longitudinally in clinical trials and observational studies. When measuring each outcome longitudinally, observed changes may be potentially confounded by variability in MRI acquisition parameters between scans. In order to accurately model longitudinal change, the acquisition parameters should thus be considered in statistical models. In this paper, several models for including protocol as well as individual MRI acquisition parameters in linear mixed models were compared using a large dataset of 3453 longitudinal MRI scans from 1341 subjects enrolled in the CLIMB study, and model fit indices were compared across the models. The model that best explained the variance in BPF data was a random intercept and random slope with protocol specific residual variance along with the following fixed-effects: baseline age, baseline disease duration, protocol and study time. The model that best explained the variance in T2LV was a random intercept and random slope along with the following fixed-effects: baseline age, baseline disease duration, protocol and study time. In light of these findings, future studies pertaining to BPF and T2LV outcomes should carefully account for the protocol factors within longitudinal models to ensure that the disease trajectory of MS subjects can be assessed more accurately. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Chua, Alicia S.; Egorova, Svetlana; Anderson, Mark C.; Polgar-Turcsanyi, Mariann; Chitnis, Tanuja; Weiner, Howard L.; Guttmann, Charles R. G.; Bakshi, Rohit; Healy, Brian C.] Brigham & Womens Hosp, Partners Multiple Sclerosis Ctr, Boston, MA 02115 USA. [Egorova, Svetlana; Chitnis, Tanuja; Weiner, Howard L.; Bakshi, Rohit; Healy, Brian C.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Healy, Brian C.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Guttmann, Charles R. G.; Bakshi, Rohit] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Healy, BC (reprint author), Partners Multiple Sclerosis Ctr, 1 Brookline Pl,Suite 602, Brookline, MA 02445 USA. EM bchealy@partners.org OI Chua, Alicia/0000-0001-6908-8539 FU Nancy Davis Foundation; Merck Serono S.A. FX The CLIMB study is funded in part by the Nancy Davis Foundation and Merck Serono S.A. NR 26 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2015 VL 8 BP 606 EP 610 DI 10.1016/j.nicl.2015.06.009 PG 5 WC Neuroimaging SC Neurosciences & Neurology GA DI0LE UT WOS:000373187100064 PM 26199872 ER PT J AU Stolz, L O'Brien, KM Miller, ML Winters-Brown, ND Blaivas, M Adhikari, S AF Stolz, Lori O'Brien, Kathleen M. Miller, Marc L. Winters-Brown, Nicole D. Blaivas, Michael Adhikari, Srikar TI A Review of Lawsuits Related to Point-of-Care Emergency Ultrasound Applications SO WESTERN JOURNAL OF EMERGENCY MEDICINE LA English DT Review DE point-of-care ultrasound; malpractice; emergency physician ID PHYSICIANS; TRIAL; RISK AB Introduction: New medical technology brings the potential of lawsuits related to the usage of that new technology. In recent years the use of point-of-care (POC) ultrasound has increased rapidly in the emergency department (ED). POC ultrasound creates potential legal risk to an emergency physician (EP) either using or not using this tool. The aim of this study was to quantify and characterize reported decisions in lawsuits related to EPs performing POC ultrasound. Methods: We conducted a retrospective review of all United States reported state and federal cases in the Westlaw database. We assessed the full text of reported cases between January 2008 and December 2012. EPs with emergency ultrasound fellowship training reviewed the full text of each case. Cases were included if an EP was named, the patient encounter was in the emergency department, the interpretation or failure to perform an ultrasound was a central issue and the application was within the American College of Emergency Physician (ACEP) ultrasound core applications. In order to assess deferred risk, cases that involved ultrasound examinations that could have been performed by an EP but were deferred to radiology were included. Results: We identified five cases. All reported decisions alleged a failure to perform an ultrasound study or a failure to perform it in a timely manner. All studies were within the scope of emergency medicine and were ACEP emergency ultrasound core applications. A majority of cases (n=4) resulted in a patient death. There were no reported cases of failure to interpret or misdiagnoses. Conclusion: In a five-year period from January 2008 through December 2012, five malpractice cases involving EPs and ultrasound examinations that are ACEP core emergency ultrasound applications were documented in the Westlaw database. All cases were related to failure to perform an ultrasound study or failure to perform a study in a timely manner and none involved failure to interpret or misdiagnosis when using of POC ultrasound. C1 [Stolz, Lori; Adhikari, Srikar] Univ Arizona, Dept Emergency Med, Tucson, AZ USA. [O'Brien, Kathleen M.] Massachusetts Gen Hosp, Div Global Hlth & Human Rights, Boston, MA 02114 USA. [Miller, Marc L.] Univ Arizona, James E Roger Coll Law, Tucson, AZ USA. [Winters-Brown, Nicole D.] Amer Univ, Washington Coll Law, Washington, DC 20016 USA. [Blaivas, Michael] St Francis Hosp, Dept Emergency Med, Columbus, GA USA. RP Stolz, L (reprint author), 1609 N Warren Ave,Room 118,POB 2405057, Tucson, AZ 85724 USA. EM lstolz@aemrc.arizona.edu NR 11 TC 2 Z9 2 U1 0 U2 0 PU WESTJEM PI ORANGE PA C/O SHAHRAM LOTFIPOUR, MD, MPH, 333 CITY BLVD W STE 640, RT 128-01, ORANGE, CA 92868 USA SN 1936-900X EI 1936-9018 J9 WEST J EMERG MED JI West. J. Emerg. Med. PD JAN PY 2015 VL 16 IS 1 BP 1 EP 4 DI 10.5811/westjem.2014.11.23592 PG 4 WC Emergency Medicine SC Emergency Medicine GA DH9IH UT WOS:000373109200001 PM 25671000 ER PT J AU Wen, LS Espinola, JA Mosowsky, JM Camargo, CA AF Wen, Leana S. Espinola, Janice A. Mosowsky, Joshua M. Camargo, Carlos A., Jr. TI Do Emergency Department Patients Receive a Pathological Diagnosis? A Nationally-Representative Sample SO WESTERN JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE health policy; clinical decision-making; patient satisfaction; diagnosis; emergency medicine ID UNSCHEDULED RETURNS AB Introduction: Understanding the cause of patients' symptoms often requires identifying a pathological diagnosis. A single-center study found that many patients discharged from the emergency department (ED) do not receive a pathological diagnosis. We analyzed 17 years of data from the National Hospital Ambulatory Medical Care Survey (NHAMCS) to identify the proportion of patients who received a pathological diagnosis at ED discharge. We hypothesized that many patients do not receive a pathological diagnosis, and that the proportion of pathological diagnoses increased between 1993 and 2009. Methods: Using the NHAMCS data from 1993-2009, we analyzed visits of patients age >= 18 years, discharged from the ED, who had presented with the three most common chief complaints: chest pain, abdominal pain, and headache. Discharge diagnoses were coded as symptomatic versus pathological based on a pre-defined coding system. We compared weighted annual proportions of pathological discharge diagnoses with 95% CIs and used logistic regression to test for trend. Results: Among 299,919 sampled visits, 44,742 met inclusion criteria, allowing us to estimate that there were 164 million adult ED visits presenting with the three chief complaints and then discharged home. Among these visits, the proportions with pathological discharge diagnosis were 55%, 71%, and 70% for chest pain, abdominal pain, and headache, respectively. The total proportion of those with a pathological discharge diagnosis decreased between 1993 and 2009, from 72% (95% CI, 69-75%) to 63% (95% CI, 59-66%). In the multivariable logistic regression model, those more likely to receive pathological diagnoses were females, African-American as compared to Caucasian, and self-pay patients. Those more likely to receive a symptomatic diagnosis were patients aged 30-79 years, with visits to EDs in the South or West regions, and seen by a physician in the ED. Conclusion: In this analysis of a nationally-representative database of ED visits, many patients were discharged from the ED without a pathological diagnosis that explained the likely cause of their symptoms. Despite advances in diagnostic testing, the proportion of pathological discharge diagnoses decreased. Future studies should investigate reasons for not providing a pathological diagnosis and how this may affect clinical outcomes. C1 [Wen, Leana S.] George Washington Univ, Dept Emergency Med, 2120 L St NW Suite 450, Washington, DC 20032 USA. [Espinola, Janice A.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Mosowsky, Joshua M.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Wen, LS (reprint author), George Washington Univ, Dept Emergency Med, 2120 L St NW Suite 450, Washington, DC 20032 USA. EM wen.leana@gmail.com NR 8 TC 1 Z9 1 U1 0 U2 0 PU WESTJEM PI ORANGE PA C/O SHAHRAM LOTFIPOUR, MD, MPH, 333 CITY BLVD W STE 640, RT 128-01, ORANGE, CA 92868 USA SN 1936-900X EI 1936-9018 J9 WEST J EMERG MED JI West. J. Emerg. Med. PD JAN PY 2015 VL 16 IS 1 BP 50 EP 54 DI 10.5811/westjem.2014.12.23474 PG 5 WC Emergency Medicine SC Emergency Medicine GA DH9IH UT WOS:000373109200009 PM 25671008 ER PT J AU White, BA Chang, YC Grabowski, BG Brown, DFM AF White, Benjamin A. Chang, Yuchiao Grabowski, Beth G. Brown, David F. M. TI In Response to: "Using Lean-Based Systems Engineering to Increase Capacity in the Emergency Department Reply SO WESTERN JOURNAL OF EMERGENCY MEDICINE LA English DT Letter C1 [White, Benjamin A.; Chang, Yuchiao; Grabowski, Beth G.; Brown, David F. M.] Massachusetts Gen Hosp, Dept Emergency Med, Zero Emerson Pl 3b, Boston, MA 02114 USA. RP White, BA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Zero Emerson Pl 3b, Boston, MA 02114 USA. EM bwhite3@partners.org NR 0 TC 0 Z9 0 U1 0 U2 1 PU WESTJEM PI ORANGE PA C/O SHAHRAM LOTFIPOUR, MD, MPH, 333 CITY BLVD W STE 640, RT 128-01, ORANGE, CA 92868 USA SN 1936-900X EI 1936-9018 J9 WEST J EMERG MED JI West. J. Emerg. Med. PD JAN PY 2015 VL 16 IS 1 BP 210 EP 211 PG 2 WC Emergency Medicine SC Emergency Medicine GA DH9IH UT WOS:000373109200045 PM 25671044 ER PT S AU Ghassemi, MM Amorim, E Pati, SB Mark, RG Brown, EN Purdon, PL Westover, MB AF Ghassemi, Mohammad M. Amorim, Edilberto Pati, Sandipan B. Mark, Roger G. Brown, Emery N. Purdon, Patrick L. Westover, M. Brandon GP IEEE TI An Enhanced Cerebral Recovery Index For Coma Prognostication Following Cardiac Arrest SO 2015 37TH 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 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) CY AUG 25-29, 2015 CL Milan, ITALY ID EEG; PROGNOSIS; ISCHEMIA; RATS AB Prognostication of coma outcomes following cardiac arrest is both qualitative and poorly understood in current practice. Existing quantitative metrics are powerful, but lack rigorous approaches to classification. This is due, in part, to a lack of available data on the population of interest. In this paper we describe a novel retrospective data set of 167 cardiac arrest patients (spanning three institutions) who received electroencephalography (EEG) monitoring. We utilized a subset of the collected data to generate features that measured the connectivity, complexity and category of EEG activity. A subset of these features was included in a logistic regression model to estimate a dichotomized cerebral performance category score at discharge. We compared the predictive performance of our method against an established EEG-based alternative, the Cerebral Recovery Index (CRI) [1] and show that our approach more reliably classifies patient outcomes, with an average increase in AUC of 0.27. C1 [Ghassemi, Mohammad M.; Mark, Roger G.; Brown, Emery N.] MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Amorim, Edilberto; Brown, Emery N.; Purdon, Patrick L.; Westover, M. Brandon] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pati, Sandipan B.] Univ Alabama Birmingham, Sch Med, Birmingham, AL 35233 USA. RP Ghassemi, MM (reprint author), MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM ghassemi@mit.edu NR 13 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-9270-1 J9 IEEE ENG MED BIO PY 2015 BP 534 EP 537 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BE4HD UT WOS:000371717200136 ER PT S AU Prasad, V Toschi, N Canichella, A Marcellucci, M Coniglione, F Dauri, M Guerrisi, M Heldt, T AF Prasad, Varesh Toschi, Nicola Canichella, Antonio Marcellucci, Martina Coniglione, Filadelfo Dauri, Mario Guerrisi, Maria Heldt, Thomas GP IEEE TI Intraoperative hemodynamics predict postoperative mortality in orthotopic liver transplantation SO 2015 37TH 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 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) CY AUG 25-29, 2015 CL Milan, ITALY ID STROKE VOLUME VARIATION; FAILURE AB Liver transplantation remains the only curative treatment option for a variety of end-stage liver diseases. Prediction of major adverse events following surgery has traditionally focused on static predictors that are known prior to surgery. The effects of intraoperative management can now be explored due to the archiving of high-resolution monitoring data. We extracted intraoperative hemodynamic trend data of 55 patients undergoing orthotopic liver transplantation (OLT) and computed 12 features from the systolic arterial blood pressure (ABP), cardiac index, central venous pressure (CVP), and stroke volume variation (SVV) signals. Using a logistic regression classifier with a leave-one-out cross-validation procedure, we selected subsets of these features to predict mortality up to 180 days after surgery. Best performance was achieved with a combination of 3 features - median absolute deviation (MAD) of ABP, median CVP, and time spent with SVV < 10% - reaching an area under the receiver-operating characteristic (or c-statistic) of 0.808. Odds ratios (OR) computed from the coefficients of the multivariate logistic regression model constructed from these features showed that greater time spent with SVV < 10% (OR = 0.981 min(-1), p = 0.001) and greater MAD of systolic ABP (OR = 0.696 mmHg(-1), p = 0.026) were significantly associated with survival. Adding preoperative measures such as age and serum concentrations of albumin, bilirubin, and creatinine failed to improve performance of the prediction model. These results show that the course of intraoperative hemodynamics can predict 180-day mortality after OLT. C1 [Prasad, Varesh] MIT, Harvard MIT Div Hlth Sci & Technol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Toschi, Nicola; Canichella, Antonio; Guerrisi, Maria] Univ Roma Tor Vergata, Dept Biomed & Prevent, Med Phys Sect, Rome, Italy. [Toschi, Nicola] Massachusetts Gen Hosp, Dept Radiol, Athinoula Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Toschi, Nicola] Harvard Univ, Sch Med, Boston, MA USA. [Marcellucci, Martina; Coniglione, Filadelfo; Dauri, Mario] Univ Hosp, Dept Emergency & Crit Care Med, Rome, Italy. [Marcellucci, Martina; Coniglione, Filadelfo] Univ Roma Tor Vergata, Rome, Italy. [Heldt, Thomas] MIT, Inst Med Engn & Sci, Cambridge, MA USA. [Heldt, Thomas] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA USA. RP Prasad, V (reprint author), MIT, Harvard MIT Div Hlth Sci & Technol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM thomas@mit.edu RI Toschi, Nicola/J-2555-2012 OI Toschi, Nicola/0000-0003-1929-5833 NR 10 TC 0 Z9 0 U1 2 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-9270-1 J9 IEEE ENG MED BIO PY 2015 BP 989 EP 992 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BE4HD UT WOS:000371717201071 ER PT S AU Coelli, S Sclocco, R Barbieri, R Reni, G Zucca, C Bianchi, AM AF Coelli, Stefania Sclocco, Roberta Barbieri, Riccardo Reni, Gianluigi Zucca, Claudio Bianchi, Anna Maria GP IEEE TI EEG-based index for engagement level monitoring during sustained attention SO 2015 37TH 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 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) CY AUG 25-29, 2015 CL Milan, ITALY ID ADAPTIVE AUTOMATION SYSTEM; TRACKING TASK AB This paper investigates the relation between mental engagement level and sustained attention in 9 healthy adults performing a Conners' "not-X" continuous performance test (CPT), while their electroencephalographic (EEG) activity was simultaneously acquired. Spectral powers were estimated and extracted in the classical EEG frequency bands. The engagement index (beta/alpha) was calculated employing four different cortical montages suggested by the literature. Results show the efficacy of the estimated measures in detecting changes in mental state and its correlation with subject reaction times throughout the test. Moreover, the influence of the recording sites was proved underling the role of frontal cortex in maintaining a constant sustained attention level. C1 [Coelli, Stefania; Sclocco, Roberta; Bianchi, Anna Maria] Politecn Milan, Dept Elect Informat & Bioengn, I-20133 Milan, Italy. [Barbieri, Riccardo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Cambridge, MA 02138 USA. [Reni, Gianluigi] IRCCS E Medea, Bioengn Lab, Bosisio Parini, Lecco, Italy. [Zucca, Claudio] IRCCS E Medea, Clin Neurophysiol Unit, Bosisio Parini, Lecco, Italy. RP Coelli, S (reprint author), Politecn Milan, Dept Elect Informat & Bioengn, I-20133 Milan, Italy. EM stefania.coelli@polimi.it; roberta.sclocco@polimi.it; barbieri@neurostat.mit.edu; gianluigi.reni@bp.lnf.it; claudio.zucca@bp.lnf.it; annamaria.bianchi@polimi.it OI Reni, Gianluigi/0000-0003-0822-3287 NR 14 TC 1 Z9 1 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-9270-1 J9 IEEE ENG MED BIO PY 2015 BP 1512 EP 1515 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BE4HD UT WOS:000371717201197 ER PT S AU Valenza, G Wendt, H Kiyono, K Hayano, J Watanabe, E Yamamoto, Y Abry, P Barbieri, R AF Valenza, G. Wendt, H. Kiyono, K. Hayano, J. Watanabe, E. Yamamoto, Y. Abry, P. Barbieri, R. GP IEEE TI Point-Process High-Resolution Representations of Heartbeat Dynamics for Multiscale Analysis: a CHF Survivor Prediction Study SO 2015 37TH 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 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) CY AUG 25-29, 2015 CL Milan, ITALY ID RATE-VARIABILITY; MORTALITY; FAILURE AB Multiscale analysis of human heartbeat dynamics has been proved effective in characterizeing cardiovascular control physiology in health and disease. However, estimation of multiscale properties can be affected by the interpolation procedure used to preprocess the unevenly sampled R-R intervals derived from the ECG. To this extent, in this study we propose the estimation of wavelet coefficients and wavelet leaders on the output of inhomogeneous point process models of heartbeat dynamics. The RR interval series is modeled using probability density functions (pdfs) characterizing and predicting the time until the next heartbeat event occurs, as a linear function of the past history. Multiscale analysis is then applied to the pdfs' instantaneous first order moment. The proposed approach is tested on experimental data gathered from 57 congestive heart failure (CHF) patients by evaluating the recognition accuracy in predicting survivor and non-survivor patients, and by comparing performances from the informative point-process based interpolation and non-informative spline-based interpolation. Results demonstrate that multiscale analysis of point-process high-resolution representations achieves the highest prediction accuracy of 65.45%, proving our method as a promising tool to assess risk prediction in CHF patients. C1 [Valenza, G.; Barbieri, R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. [Valenza, G.; Barbieri, R.] MIT, Cambridge, MA 02139 USA. [Valenza, G.] Univ Pisa, Res Ctr E Piaggio, Pisa, Italy. [Valenza, G.] Univ Pisa, Dept Informat Engn, Pisa, Italy. [Wendt, H.] Univ Toulouse, CNRS, IRIT ENSEEIHT, Toulouse, France. [Abry, P.] ENS Lyon, CNRS, Dept Phys, Lyon, France. [Kiyono, K.] Osaka Univ, Suita, Osaka 565, Japan. [Hayano, J.] Nagoya City Univ, Grad Sch Med Sci, Dept Med Educ, Nagoya, Aichi, Japan. [Watanabe, E.] Fujita Hlth Univ, Sch Med, Dept Cardiol, Toyoake, Aichi 47011, Japan. [Yamamoto, Y.] Univ Tokyo, Tokyo 1138654, Japan. RP Valenza, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. EM gvalenza@neurostat.mit.edu; herwig.wendt@irit.fr; kiyono@bpe.es.osaka-u.ac.jp; hayano@med.nagoya-cu.ac.jp; enwatan@fujita-hu.ac.jp; yamamoto@p.u-tokyo.ac.jp; patrice.abry@ens-lyon.fr; barbieri@neurostat.mit.edu OI Abry, Patrice/0000-0002-7096-8290; Valenza, Gaetano/0000-0001-6574-1879 NR 22 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-9270-1 J9 IEEE ENG MED BIO PY 2015 BP 1951 EP 1954 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BE4HD UT WOS:000371717202060 ER PT S AU Duggento, A Bianciardi, M Wald, LL Passamonti, L Guerrisi, M Barbieri, R Toschi, N AF Duggento, Andrea Bianciardi, Marta Wald, Lawrence L. Passamonti, Luca Guerrisi, Maria Barbieri, Riccardo Toschi, Nicola GP IEEE TI Globally conditioned causality in estimating directed brain-heart interactions through joint MRI and RR series analysis SO 2015 37TH 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 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) CY AUG 25-29, 2015 CL Milan, ITALY ID GRANGER CAUSALITY; RATE-VARIABILITY; FMRI AB We used 7T fMRI with simultaneous physiological signals acquisitions to investigate the causal interactions from resting state brain activity to autonomic nervous system (ANS) outflow as quantified through a probabilistic heartbeat model. Given the highly redundant nature of brain-derived signals, we compare the results of traditional bivariate Granger Causality (GC) to a globally conditioned approach which evaluates the additional influence of each brain region on ANS activity while factoring out effects concomitantly mediated by other brain regions. The bivariate approach results in an unrealistically large number of spurious causal brain-heart links. In contrast, using the globally conditioned approac, we demonstrate the existence of significant selective causal links between cortical/subcortical brain regions and ANS outflow for sympathetic and parasympathetic modulation as well as sympathovagal balance, with a prominent involvement of frontal, parietal, and cerebellar regions and Sensory Motor, Default Mode, Left and Right executive networks. Provided proper conditioning is employed to eliminate spurious causalities, 7T functional imaging coupled with physiological signal acquisition and GC analysis is able to quantify directed brain-heart interactions reflecting central modulation of ANS outflow. C1 [Duggento, Andrea; Guerrisi, Maria; Toschi, Nicola] Univ Roma Tor Vergata, Fac Med, Dept Biomed & Prevent, Med Phys Sect, Rome, Italy. [Bianciardi, Marta; Wald, Lawrence L.; Toschi, Nicola] MGH, AA Martinos Ctr Biomed Imaging, Dept Radiol, Boston, MA USA. [Bianciardi, Marta; Wald, Lawrence L.; Toschi, Nicola] Harvard Univ, Sch Med, Boston, MA USA. [Passamonti, Luca] Univ Cambridge, Dept Clin Neurosci, Robinson Way CB2 0SZ, England. [Barbieri, Riccardo] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Barbieri, Riccardo] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Duggento, A (reprint author), Univ Roma Tor Vergata, Fac Med, Dept Biomed & Prevent, Med Phys Sect, Rome, Italy. EM duggento@med.uniroma2.it RI Toschi, Nicola/J-2555-2012; Wald, Lawrence/D-4151-2009 OI Toschi, Nicola/0000-0003-1929-5833; NR 15 TC 0 Z9 0 U1 2 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-9270-1 J9 IEEE ENG MED BIO PY 2015 BP 3795 EP 3798 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BE4HD UT WOS:000371717204020 ER PT S AU Wang, MD Guo, N Zhang, H Elfhakri, G Hu, GS Li, QZ AF Wang, Mengdie Guo, Ning Zhang, Hui Elfhakri, Georges Hu, Guangshu Li, Quanzheng GP IEEE TI Retrospective Data-driven Respiratory Gating for PET using TOF Information SO 2015 37TH 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 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) CY AUG 25-29, 2015 CL Milan, ITALY ID EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY; TIME-OF-FLIGHT; 3-DIMENSIONAL PET; LUNG LESIONS; MOTION; CT; FEASIBILITY; SCANNER; SIGNAL AB Traditional data-driven respiratory gating method is capable of detecting breathing cycles directly from positron emission tomography (PET) data, but usually fails at low SNR, particularly at low dose PET/CT study. Time-of-flight (TOF) PET has the potential to improve the SNR. In order for TOF information to reduce the statistical noise and boost the performance of respiratory gating, we present a robust data-driven respiratory gating method using TOF information, which retrospectively derived the respiratory signal from the acquired TOF-PET data. The PET data was acquired in list mode format and analyzed in sinogram space. The method was demonstrated with patient datasets acquired on a TOF PET/CT system. Data-driven gating methods by center of mass (COM) and principle component analysis (PCA) algorithm were successfully performed on nonTOF PET and TOF PET dataset. To assess the accuracy of the data-driven respiratory signal, a hardware-based signal was acquired for comparison. The study showed that retrospectively respiratory gating using TOF sinograms has improved the SNR, and outperforms the non-TOF gating under both COM and PCA algorithms. C1 [Wang, Mengdie; Zhang, Hui; Hu, Guangshu] Tsinghua Univ, Dept Biomed Engn, Beijing 100084, Peoples R China. [Wang, Mengdie; Guo, Ning; Elfhakri, Georges; Li, Quanzheng] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nucl Med & Mol Imaging,Dept Radiol, Boston, MA 02114 USA. RP Wang, MD (reprint author), Tsinghua Univ, Dept Biomed Engn, Beijing 100084, Peoples R China. EM mwang20@mgh.harvard.edu NR 26 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-9270-1 J9 IEEE ENG MED BIO PY 2015 BP 4520 EP 4523 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BE4HD UT WOS:000371717204198 ER PT S AU Sclocco, R Citi, L Garcia, RG Cerutti, S Bianchi, AM Kuo, B Napadow, V Barbieri, R AF Sclocco, Roberta Citi, Luca Garcia, Ronald G. Cerutti, Sergio Bianchi, Anna M. Kuo, Braden Napadow, Vitaly Barbieri, Riccardo GP IEEE TI Combining sudomotor nerve impulse estimation with fMRI to investigate the central sympathetic response to nausea SO 2015 37TH 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 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) CY AUG 25-29, 2015 CL Milan, ITALY ID SKIN-CONDUCTANCE RESPONSES; MOTION SICKNESS; GENERATION; BRAIN AB The skin conductance (SC) signal is one of the most important non-invasive indirect measures of autonomic outflow. Several mathematical models have been proposed in the literature to characterize specific SC features. In this work, we present a method for the estimation of central control of sudomotor nerve impulse (SMI) function using SC. The method is based on a differential formulation decomposed into two first order differential equations. We validate our estimation framework by applying it on an experimental protocol where eleven motion sickness-prone subjects were exposed to a nauseogenic visual stimulus while SC and fMRI signals were recorded. Our results show an expected significant increase in the mean amplitude of SMI peaks during the highest reported nausea, as well as a decreasing trend during recovery, which was not evident for skin conductance level. Importantly, SMI/fMRI analysis found a negative association between SMI and fMRI signal in orbitofrontal, dorsolateral prefrontal, and posterior insula cortices, consistent with previous studies correlating brain fMRI and microneurographic signals. C1 [Sclocco, Roberta; Cerutti, Sergio; Bianchi, Anna M.] Politecn Milan, Dept Elect Informat & Bioengn, Milan, Italy. [Sclocco, Roberta; Garcia, Ronald G.; Napadow, Vitaly] Harvard Univ, Massachusetts Gen Hosp, Sch Med, AA Martinos Ctr Biomed Imaging, Boston, MA USA. [Citi, Luca] Univ Essex, Sch Elect Engn & Comp Sci, Colchester CO4 3SQ, Essex, England. [Kuo, Braden] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastroenterol Unit, Boston, MA USA. [Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. RP Sclocco, R (reprint author), Politecn Milan, Dept Elect Informat & Bioengn, Milan, Italy. EM roberta.sclocco@polimi.it; lciti@essex.ac.uk; rgarcia@nmr.mgh.harvard.edu; sergio.cerutti@polimi.it; annamaria.bianchi@polimi.it; bkuo@partners.org; vitaly@nmr.mgh.harvard.edu; barbieri@neurostat.mit.edu OI Garcia, Ronald Gerardo/0000-0002-8325-9944 NR 17 TC 1 Z9 1 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-9270-1 J9 IEEE ENG MED BIO PY 2015 BP 4683 EP 4686 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BE4HD UT WOS:000371717204238 ER PT S AU Annunziata, R Kheirkhah, A Hamrah, P Trucco, E AF Annunziata, Roberto Kheirkhah, Ahmad Hamrah, Pedram Trucco, Emanuele GP IEEE TI Combining Efficient Hand-Crafted Features with Learned Filters for Fast and Accurate Corneal Nerve Fibre Centreline Detection SO 2015 37TH 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 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) CY AUG 25-29, 2015 CL Milan, ITALY AB We propose a new approach to corneal nerve fibre centreline detection for in vivo confocal microscopy images. Relying on a combination of efficient hand-crafted features and learned filters, our method offers an excellent compromise between accuracy and running time. Unlike previous solutions using sparse coding to learn small filter banks, we employ K-means to efficiently learn the high amount of filters needed to cope with the multiple challenges involved, e.g., low contrast and resolution, non-uniform illumination, tortuosity and confounding non-target structures. The use of K-means for dictionary learning allows us to learn banks of 100 filters in less than 30 seconds compared to several days needed when using sparse coding. Experimental results using a dataset including 100 images show that our approach outperforms significantly state-of-the-art methods in terms of precision-recall curves. C1 [Annunziata, Roberto; Trucco, Emanuele] Univ Dundee, Sch Comp, Comp Vis & Image Proc Grp, Dundee, Scotland. [Kheirkhah, Ahmad; Hamrah, Pedram] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Annunziata, R (reprint author), Univ Dundee, Sch Comp, Comp Vis & Image Proc Grp, Dundee, Scotland. EM r.annunziata@dundee.ac.uk NR 17 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 978-1-4244-9270-1 J9 IEEE ENG MED BIO PY 2015 BP 5655 EP 5658 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BE4HD UT WOS:000371717205227 ER PT S AU Gee, AH Barbieri, R Paydarfar, D Indic, P AF Gee, Alan H. Barbieri, Riccardo Paydarfar, David Indic, Premananda GP IEEE TI Uncovering Statistical Features of Bradycardia Severity in Premature Infants Using a Point Process Model SO 2015 37TH 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 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) CY AUG 25-29, 2015 CL Milan, ITALY ID PRETERM INFANTS; APNEA; EPISODES AB Premature infants are susceptible to a variety of life-threatening events. Underdeveloped cardiovascular control due to an immature autonomic nervous system can lead to recurrent bradycardias that reduce blood flow and oxygen to critical organs, and result in long-term developmental disabilities or sudden death. In this study, we investigate the use of a novel point process framework to model heart rate dynamics in premature infants, including the full range of bradycardia severity. We find that the lognormal distribution accurately models the R-R interval time series, due to the long-tail nature of the distribution. We also find that the degree of bradycardia severity is correlated with distinct clustering features of the point-process indices in regions encompassing and adjacent to bradycardias. This underlying property in heart rate dynamics may provide valuable statistical information for quantifying the vulnerability of premature infants to develop bradycardia. C1 [Gee, Alan H.; Paydarfar, David] Harvard Univ, Wyss Inst, Boston, MA 02115 USA. [Barbieri, Riccardo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Barbieri, Riccardo] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Paydarfar, David; Indic, Premananda] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01655 USA. RP Gee, AH (reprint author), Harvard Univ, Wyss Inst, Boston, MA 02115 USA. EM Alan.Gee@wyss.harvard.edu; Barbieri@neurostat.mit.edu; David.Paydarfar@umassmed.edu; Premananda.Indic@umassmed.edu NR 12 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-9270-1 J9 IEEE ENG MED BIO PY 2015 BP 5855 EP 5858 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BE4HD UT WOS:000371717206031 ER PT S AU Biswal, S Nip, Z Junior, V Bianchi, MT Rosenthal, ES Westover, MB AF Biswal, Siddharth Nip, Zarina Moura Junior, Valdcry Bianchi, Matt T. Rosenthal, Eric S. Westover, M. Brandon GP IEEE TI Automated Information Extraction from Free-Text EEG Reports SO 2015 37TH 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 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) CY AUG 25-29, 2015 CL Milan, ITALY ID CLASSIFICATION AB In this study we have developed a supervised learning to automatically detect with high accuracy EEG reports that describe seizures and epileptiform discharges. We manually labeled 3,277 documents as describing one or more seizures vs no seizures, and as describing epileptiform discharges vs no epileptiform discharges. We then used Naive Bayes to develop a system able to automatically classify EEG reports into these categories. Our system consisted of normalization techniques, extraction of key sentences, and automated feature selection using cross validation. As candidate features we used key words and special word patterns called elastic word sequences (EWS). Final feature selection was accomplished via sequential backward selection. We used cross validation to predict out of sample performance. Our automated feature selection procedure resulted in a classifier with 38 features for seizure detection, and 23 features for epileptiform discharge detection. The average [95% CI] area under the receiver operating curve was 99.05 [98.79, 99.32]% for detecting reports with seizures, and 96.15 [92.31, 100.00]% for detecting reports with epileptiform discharges. The methodology described herein greatly reduces the manual labor involved in identifying large cohorts of patients for retrospective neurophysiological studies of patients with epilepsy. C1 [Biswal, Siddharth; Nip, Zarina; Moura Junior, Valdcry; Bianchi, Matt T.; Rosenthal, Eric S.; Westover, M. Brandon] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Westover, MB (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM mwestover@mgh.harvard.edu NR 12 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-9270-1 J9 IEEE ENG MED BIO PY 2015 BP 6804 EP 6807 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BE4HD UT WOS:000371717207021 ER PT S AU Zhou, DW Westover, MB McClain, LM Nagaraj, SB Bajwa, EK Quraishi, SA Akeju, O Cobb, JP Purdon, PL AF Zhou, David W. Westover, M. Brandon McClain, Lauren M. Nagaraj, Sunil B. Bajwa, Ednan K. Quraishi, Sadeq A. Akeju, Oluwaseun Cobb, J. Perren Purdon, Patrick L. GP IEEE TI Clustering analysis to identify distinct spectral components of encephalogram burst suppression in critically ill patients SO 2015 37TH 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 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) CY AUG 25-29, 2015 CL Milan, ITALY ID SEVERE SEPSIS; MORTALITY AB Millions of patients are admitted each year to intensive care units (ICUs) in the United States. A significant fraction of ICU survivors develop life-long cognitive impairment, incurring tremendous financial and societal costs. Delirium, a state of impaired awareness, attention and cognition that frequently develops during ICU care, is a major risk factor for post-ICU cognitive impairment. Recent studies suggest that patients experiencing electroencephalogram (EEG) burst suppression have higher rates of mortality and are more likely to develop delirium than patients who do not experience burst suppression. Burst suppression is typically associated with coma and deep levels of anesthesia or hypothermia, and is defined clinically as an alternating pattern of high-amplitude "burst" periods interrupted by sustained low-amplitude "suppression" periods. Here we describe a clustering method to analyze EEG spectra during burst and suppression periods. We used this method to identify a set of distinct spectral patterns in the EEG during burst and suppression periods in critically ill patients. These patterns correlate with level of patient sedation, quantified in terms of sedative infusion rates and clinical sedation scores. This analysis suggests that EEG burst suppression in critically ill patients may not be a single state, but instead may reflect a plurality of states whose specific dynamics relate to a patient's underlying brain function. C1 [Zhou, David W.; Quraishi, Sadeq A.; Akeju, Oluwaseun; Cobb, J. Perren; Purdon, Patrick L.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Westover, M. Brandon; McClain, Lauren M.; Nagaraj, Sunil B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Zhou, DW (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM patrickp@nmr.mgh.harvard.edu; mwestover@mgh.harvard.edu NR 12 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-9270-1 J9 IEEE ENG MED BIO PY 2015 BP 7258 EP 7261 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BE4HD UT WOS:000371717207132 ER PT S AU Deng, XY Faghih, RT Barbieri, R Paulk, AC Asaad, WF Brown, EN Dougherty, DD Widge, AS Eskandar, EN Eden, UT AF Deng, Xinyi Faghih, Rose T. Barbieri, Riccardo Paulk, Angelique C. Asaad, Wael F. Brown, Emery N. Dougherty, Darin D. Widge, Alik S. Eskandar, Emad N. Eden, Uri T. GP IEEE TI Estimating a Dynamic State to Relate Neural Spiking Activity to Behavioral Signals during Cognitive Tasks SO 2015 37TH 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 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) CY AUG 25-29, 2015 CL Milan, ITALY ID TRAIN DATA-ANALYSIS; CAUDATE-NUCLEUS; PREFRONTAL CORTEX AB An important question in neuroscience is understanding the relationship between high-dimensional electrophysiological data and complex, dynamic behavioral data. One general strategy to address this problem is to define a low-dimensional representation of essential cognitive features describing this relationship. Here we describe a general state-space method to model and fit a low-dimensional cognitive state process that allows us to relate behavioral outcomes of various tasks to simultaneously recorded neural activity across multiple brain areas. In particular, we apply this model to data recorded in the lateral prefrontal cortex (PFC) and caudate nucleus of non-human primates as they perform learning and adaptation in a rule-switching task. First, we define a model for a cognitive state process related to learning, and estimate the progression of this learning state through the experiments. Next, we formulate a point process generalized linear model to relate the spiking activity of each PFC and caudate neuron to the stimated learning state. Then, we compute the posterior densities of the cognitive state using a recursive Bayesian decoding algorithm. We demonstrate that accurate decoding of a learning state is possible with a simple point process model of population spiking. Our analyses also allow us to compare decoding accuracy across neural populations in the PFC and caudate nucleus. C1 [Deng, Xinyi] Boston Univ, Grad Program Stat, Boston, MA 02215 USA. [Faghih, Rose T.; Brown, Emery N.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Faghih, Rose T.] MIT, Neurosci Stat Res Lab, Cambridge, MA 02139 USA. [Faghih, Rose T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. [Barbieri, Riccardo] MIT, Cambridge, MA 02139 USA. [Paulk, Angelique C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. [Asaad, Wael F.] Brown Univ, Alpert Med Sch, Dept Neurosurg, Providence, RI 02912 USA. [Asaad, Wael F.] Brown Univ, Alpert Med Sch, Dept Neurosci, Providence, RI 02912 USA. [Asaad, Wael F.] Rhode Isl Hosp, Providence, RI 02912 USA. [Brown, Emery N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. [Brown, Emery N.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. [Dougherty, Darin D.; Widge, Alik S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Widge, Alik S.] MIT, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. [Eskandar, Emad N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nayef Al Rodhan Labs,Dept Neurosurg, Boston, MA 02114 USA. [Eden, Uri T.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. RP Deng, XY (reprint author), Boston Univ, Grad Program Stat, Boston, MA 02215 USA. EM xinyi@math.bu.edu; rfaghih@mit.edu; barbieri@neurostat.mit.edu; apaulk@mgh.harvard.edu; wael_asaad@brown.edu; enb@neurostat.mit.edu; ddougherty@partners.org; awidge@partners.org; eeskandar@mgh.harvard.edu; tzvi@bu.edu NR 27 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-9270-1 J9 IEEE ENG MED BIO PY 2015 BP 7808 EP 7813 PG 6 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BE4HD UT WOS:000371717208023 ER PT S AU Faghih, RT Stokes, PA Marin, MF Zsido, RG Zorowitz, S Rosenbaum, BL Song, HJ Milad, MR Dougherty, DD Eskandar, EN Widge, AS Brown, EN Barbieri, R AF Faghih, Rose T. Stokes, Patrick A. Marin, Marie-France Zsido, Rachel G. Zorowitz, Sam Rosenbaum, Blake L. Song, Huijin Milad, Mohammed R. Dougherty, Darin D. Eskandar, Emad N. Widge, Alik S. Brown, Emery N. Barbieri, Riccardo GP IEEE TI Characterization of Fear Conditioning and Fear Extinction by Analysis of Electrodermal Activity SO 2015 37TH 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 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) CY AUG 25-29, 2015 CL Milan, ITALY ID SKIN-CONDUCTANCE; INHIBITION; ALGORITHM; RESPONSES; FOCUSS; PTSD AB Electrodermal activity (EDA) is a measure of physical arousal, which is frequently measured during psychophysical tasks relevant for anxiety disorders. Recently, specific protocols and procedures have been devised in order to examine the neural mechanisms of fear conditioning and extinction. EDA reflects important responses associated with stimuli specifically administrated during these procedures. Although several previous studies have demonstrated the reproducibility of measures estimated from EDA, a mathematical framework associated with the stimulus-response experiments in question and, at the same time, including the underlying emotional state of the subject during fear conditioning and/or extinction experiments is not well studied. We here propose an ordinary differential equation model based on sudomotor nerve activity, and estimate the fear eliciting stimulus using a compressed sensing algorithm. Our results show that we are able to recover the underlying stimulus (visual cue or mild electrical shock). Moreover, relating the time-delay in the estimated stimulation to the visual cue during extinction period shows that fear level decreases as visual cues are presented without shock, suggesting that this feature might be used to estimate the fear state. These findings indicate that a mathematical model based on electrodermal responses might be critical in defining a low-dimensional representation of essential cognitive features in order to describe dynamic behavioral states. C1 [Faghih, Rose T.; Stokes, Patrick A.; Widge, Alik S.; Brown, Emery N.; Barbieri, Riccardo] MIT, Cambridge, MA 02139 USA. [Faghih, Rose T.; Stokes, Patrick A.; Marin, Marie-France; Zsido, Rachel G.; Zorowitz, Sam; Rosenbaum, Blake L.; Song, Huijin; Milad, Mohammed R.; Dougherty, Darin D.; Eskandar, Emad N.; Widge, Alik S.; Brown, Emery N.; Barbieri, Riccardo] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Faghih, RT (reprint author), MIT, Cambridge, MA 02139 USA. EM rfaghih@mit.edu NR 18 TC 0 Z9 0 U1 4 U2 4 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-9270-1 J9 IEEE ENG MED BIO PY 2015 BP 7814 EP 7818 PG 5 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BE4HD UT WOS:000371717208024 ER PT S AU Yousefi, A Paulk, AC Deckersbach, T Dougherty, DD Eskandar, EN Widge, AS Eden, UT AF Yousefi, Ali Paulk, Angelique C. Deckersbach, Thilo Dougherty, Darin D. Eskandar, Emad N. Widge, Alik S. Eden, Uri T. GP IEEE TI Cognitive State Prediction Using an EM Algorithm Applied to Gamma Distributed Data SO 2015 37TH 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 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) CY AUG 25-29, 2015 CL Milan, ITALY ID DYNAMIC-ANALYSIS; INTERFERENCE AB Behavioral tests are widely used to quantify features of cognitive processing. For a large class of behavioral signals, the observed variables are non-Gaussian and dynamic; classical estimation algorithms are ill-suited to modeling such data. In this research, we propose a mathematical framework to predict a cognitive state variable related to behavioral signals, which are best modeled using a Gamma distribution. The proposed algorithm combines a Gamma Smoother and EM algorithm in the prediction process. The algorithm is applied to reaction time recorded from subjects performing a Multi-Source Interference Task (MSIT) to dynamically quantify their cognitive flexibility through the course of the experiment. C1 [Yousefi, Ali; Paulk, Angelique C.; Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurol Surg, Boston, MA 02114 USA. [Yousefi, Ali; Paulk, Angelique C.; Deckersbach, Thilo; Dougherty, Darin D.; Eskandar, Emad N.; Widge, Alik S.] Harvard Univ, Sch Med, Boston, MA USA. [Yousefi, Ali; Eden, Uri T.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Deckersbach, Thilo; Dougherty, Darin D.; Widge, Alik S.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Widge, Alik S.] MIT, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. RP Yousefi, A (reprint author), Massachusetts Gen Hosp, Dept Neurol Surg, Boston, MA 02114 USA. EM ayousefi@mgh.harvard.edu NR 16 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 978-1-4244-9270-1 J9 IEEE ENG MED BIO PY 2015 BP 7819 EP 7824 PG 6 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BE4HD UT WOS:000371717208025 ER PT S AU Bjune, CK Marinis, TF Brady, JM Moran, J Wheeler, J Sriram, TS Parks, PD Widge, AS Dougherty, DD Eskandar, EN AF Bjune, Caroline K. Marinis, Thomas F. Brady, Jeanne M. Moran, James Wheeler, Jesse Sriram, Tirunelveli S. Parks, Philip D. Widge, Alik S. Dougherty, Darin D. Eskandar, Emad N. GP IEEE TI Package Architecture and Component Design for an Implanted Neural Stimulator with Closed Loop Control SO 2015 37TH 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 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) CY AUG 25-29, 2015 CL Milan, ITALY DE Neural stimulation; Deep brain; Neural interfaces; Implantable systems; Neural interfaces; Microsystems and microfabrication ID TELEMETRY AB An implanted neural stimulator with closed loop control requires electrodes for stimulation pulses and recording neuron activity. Our system features arrays of 64 electrodes. Each electrode can be addressed through a cross bar switch, to enable it to be used for stimulation or recording. This electrode switch,, a bank of low noise amplifiers with an integrated analog to digital converter, power conditioning electronics, and a communications and control gate array are co-located with the electrode array in a 14 millimeter diameter satellite package that is designed to be flush mounted in a skull burr hole. Our system features five satellite packages connected to a central hub processor-controller via ten conductor cables that terminate in a custom designed, miniaturized connector. The connector incorporates features of high reliability, military grade devices and utilizes three distinct seals to isolate the contacts from fluid permeation. The hub system is comprised of a connector header, hermetic electronics package, and rechargeable battery pack, which are mounted on and electrically interconnected by a flexible circuit board. The assembly is over molded with a compliant silicone rubber. The electronics package contains two antennas, a large coil, used for recharging the battery and a high bandwidth antenna that is used to download data and update software. The package is assembled from two machined alumina pieces, a flat base with brazed in, electrical feed through pins and a rectangular cover with rounded corners. Titanium seal rings are brazed onto these two pieces so that they can be sealed by laser welding. A third system antenna is incorporated in the flexible circuit board. It is used to communicate with an externally worn control package, which monitors the health of the system and allows both the user and clinician to control or modify various system function parameters. C1 [Bjune, Caroline K.; Marinis, Thomas F.; Brady, Jeanne M.; Moran, James; Wheeler, Jesse; Sriram, Tirunelveli S.; Parks, Philip D.] Charles Stark Draper Lab, Cambridge, MA USA. [Widge, Alik S.; Dougherty, Darin D.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Widge, Alik S.; Dougherty, Darin D.; Eskandar, Emad N.] Harvard Univ, Sch Med, Boston, MA USA. [Widge, Alik S.] MIT, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. [Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurol Surg, Boston, MA 02114 USA. RP Bjune, CK (reprint author), Charles Stark Draper Lab, Cambridge, MA USA. EM pparks@draper.com NR 6 TC 1 Z9 1 U1 4 U2 5 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-9270-1 J9 IEEE ENG MED BIO PY 2015 BP 7825 EP 7830 PG 6 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BE4HD UT WOS:000371717208026 ER PT S AU Hamilton, L McConley, M Angermueller, K Goldberg, D Corba, M Kim, L Moran, J Parks, PD Chin, S Widge, AS Dougherty, DD Eskandar, EN AF Hamilton, Lei McConley, Marc Angermueller, Kai Goldberg, David Corba, Massimiliano Kim, Louis Moran, James Parks, Philip D. Chin, Sang (Peter) Widge, Alik S. Dougherty, Darin D. Eskandar, Emad N. GP IEEE TI Neural Signal Processing and Closed-loop Control Algorithm Design for an Implanted Neural Recording and Stimulation System SO 2015 37TH 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 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) CY AUG 25-29, 2015 CL Milan, ITALY DE Neural Stimulation; Neuropsychiatric Disorders; Closed-loop Control; Decode; Signal Processing ID ACTION-POTENTIALS AB A fully autonomous intracranial device is built to continually record neural activities in different parts of the brain, process these sampled signals, decode features that correlate to behaviors and neuropsychiatric states, and use these features to deliver brain stimulation in a closed-loop fashion. In this paper, we describe the sampling and stimulation aspects of such a device. We first describe the signal processing algorithms of two unsupervised spike sorting methods. Next, we describe the LFP time-frequency analysis and feature derivation from the two spike sorting methods. Spike sorting includes a novel approach to constructing a dictionary learning algorithm in a Compressed Sensing (CS) framework. We present a joint prediction scheme to determine the class of neural spikes in the dictionary learning framework; and, the second approach is a modified OSort algorithm which is implemented in a distributed system optimized for power efficiency. Furthermore, sorted spikes and time-frequency analysis of LFP signals can be used to generate derived features (including cross-frequency coupling, spike-field coupling). We then show how these derived features can be used in the design and development of novel decode and closed-loop control algorithms that are optimized to apply deep brain stimulation based on a patient's neuropsychiatric state. For the control algorithm, we define the state vector as representative of a patient's impulsivity, avoidance, inhibition, etc. Controller parameters are optimized to apply stimulation based on the state vector's current state as well as its historical values. The overall algorithm and software design for our implantable neural recording and stimulation system uses an innovative, adaptable, and reprogrammable architecture that enables advancement of the state-of-the-art in closed-loop neural control while also meeting the challenges of system power constraints and concurrent development with ongoing scientific research designed to define brain network connectivity and neural network dynamics that vary at the individual patient level and vary over time. C1 [Hamilton, Lei; McConley, Marc; Angermueller, Kai; Goldberg, David; Corba, Massimiliano; Kim, Louis; Moran, James; Parks, Philip D.; Chin, Sang (Peter)] Charles Stark Draper Lab, Cambridge, MA USA. [Widge, Alik S.; Dougherty, Darin D.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Widge, Alik S.; Dougherty, Darin D.; Eskandar, Emad N.] Harvard Univ, Sch Med, Boston, MA USA. [Widge, Alik S.] MIT, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. [Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurol Surg, Boston, MA 02114 USA. RP Hamilton, L (reprint author), Charles Stark Draper Lab, Cambridge, MA USA. EM lhamilton@draper.com NR 9 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-9270-1 J9 IEEE ENG MED BIO PY 2015 BP 7831 EP 7836 PG 6 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BE4HD UT WOS:000371717208027 ER PT S AU Wheeler, JJ Baldwin, K Kindle, A Guyon, D Nugent, B Segura, C Rodriguez, J Czarnecki, A Dispirito, HJ Lachapelle, J Parks, PD Moran, J Widge, AS Dougherty, DD Eskandar, EN AF Wheeler, Jesse J. Baldwin, Keith Kindle, Alex Guyon, Daniel Nugent, Brian Segura, Carlos Rodriguez, John Czarnecki, Andrew Dispirito, Hailey J. Lachapelle, John Parks, Philip D. Moran, James Widge, Alik S. Dougherty, Darin D. Eskandar, Emad N. GP IEEE TI An Implantable 64-channel Neural Interface with Reconfigurable Recording and Stimulation SO 2015 37TH 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 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) CY AUG 25-29, 2015 CL Milan, ITALY DE Neural stimulation; Deep brain; Neural interfaces; Implantable systems; Neural interfaces; Microsystems and microfabrication AB Next generation implantable medical devices will have the potential to provide more precise and effective therapies through adaptive closed-loop controllers that combine sensing and stimulation across larger numbers of electrode channels. A major challenge in the design of such devices is balancing increased functionality and channel counts with the miniaturization required for implantation within small anatomical spaces. Customized therapies will require adaptive systems capable of tuning which channels are sensed and stimulated to overcome variability in patient-specific needs, surgical placement of electrodes, and chronic physiological responses. In order to address these challenges, we have designed a miniaturized implantable fully-reconfigurable front-end system that is integrated into the distal end of an 8-wire lead, enabling up to 64 electrodes to be dynamically configured for sensing and stimulation. Full reconfigurability is enabled by two custom 32x2 cross-point switch (CPS) matrix ASICs which can route any electrode to either an amplifier with reprogrammable bandwidth and integrated ADC or to one of two independent stimulation channels that can be driven through the lead. The 8-wire circuit includes a digital interface for robust communication as well as a charge-balanced powering scheme for enhanced safety. The system is encased in a hermetic package designed to fit within a 14 mm bur-hole in the skull for neuromodulation of the brain, but could easily be adapted to enhance therapies across a broad spectrum of applications. C1 [Wheeler, Jesse J.; Baldwin, Keith; Kindle, Alex; Guyon, Daniel; Nugent, Brian; Segura, Carlos; Rodriguez, John; Czarnecki, Andrew; Dispirito, Hailey J.; Lachapelle, John; Parks, Philip D.; Moran, James] Charles Stark Draper Lab, Cambridge, MA USA. [Widge, Alik S.; Dougherty, Darin D.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Widge, Alik S.; Dougherty, Darin D.] Harvard Univ, Sch Med, Boston, MA USA. [Widge, Alik S.] MIT, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. [Eskandar, Emad N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol Surg, Boston, MA USA. RP Wheeler, JJ (reprint author), Charles Stark Draper Lab, Cambridge, MA USA. EM jwheeler@draper.com NR 4 TC 2 Z9 2 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-9270-1 J9 IEEE ENG MED BIO PY 2015 BP 7837 EP 7840 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BE4HD UT WOS:000371717208028 ER PT S AU Valenza, G Faes, L Citi, L Orini, M Barbieri, R AF Valenza, Gaetano Faes, Luca Citi, Luca Orini, Michele Barbieri, Riccardo GP IEEE TI Instantaneous Transfer Entropy for the Study of Cardio-Respiratory Dynamics SO 2015 37TH 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 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) CY AUG 25-29, 2015 CL Milan, ITALY ID HEART-RATE-VARIABILITY; INFORMATION-TRANSFER; ARTERIAL-PRESSURE; UP TILT; COMPLEXITY; PERIOD AB Measures of transfer entropy have been proposed to quantify the directional coupling and strength between two complex physiological variables. Particular attention has been given to nonlinear interactions within cardiovascular and respiratory dynamics as influenced by the autonomic nervous system. However, standard transfer entropy estimates have shown major limitations in dealing with issues concerning stochastic system modeling, limited observations in time, and the assumption of stationarity of the considered physiological variables. Moreover, standard estimates are unable to track time-varying changes in nonlinear coupling with high resolution in time. Here, we propose a novel definition of transfer entropy linked to inhomogeneous point-process theory. Heartbeat and respiratory dynamics are characterized through discrete time series, and modeled through probability density functions (PDFs) which characterize and predict the time until the occurrence of the next physiological event as a function of the past history. As the derived measures of entropy are instantaneously defined through continuos PDFs, a novel index (the Instantaneous point-process Transfer Entropy, ipTransfEn) is able to provide instantaneous tracking of the information transfer. The new measure is tested on experimental data gathered from 16 healthy subjects undergoing postural changes, showing fast tracking of the tilting events and low variability during the standing phase. C1 [Valenza, Gaetano; Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA USA. [Valenza, Gaetano; Barbieri, Riccardo] MIT, Cambridge, MA 02139 USA. [Valenza, Gaetano] Univ Pisa, Res Ctr E Piaggio, I-56100 Pisa, Italy. [Valenza, Gaetano] Univ Pisa, Dept Informat Engn, I-56100 Pisa, Italy. [Faes, Luca] Univ Trento, IRCS FBK, Trento, Italy. [Faes, Luca] Univ Trento, Dept Ind Engn, BIOtech, Trento, Italy. [Citi, Luca] Univ Essex, Sch Comp Sci & Elect Engn, Colchester CO4 3SQ, Essex, England. [Orini, Michele] UCL, Inst Cardiovasc Sci, London, England. RP Valenza, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA USA. EM g.valenza@ieee.org OI orini, michele/0000-0001-5773-0344; Valenza, Gaetano/0000-0001-6574-1879 NR 22 TC 2 Z9 2 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-9270-1 J9 IEEE ENG MED BIO PY 2015 BP 7885 EP 7888 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BE4HD UT WOS:000371717208040 ER PT S AU Bernabeu, MO Lu, Y Lammer, J Aiello, LP Coveney, PV Sun, JK AF Bernabeu, Miguel O. Lu, Yang Lammer, Jan Aiello, Lloyd P. Coveney, Peter V. Sun, Jennifer K. GP IEEE TI Characterization of Parafoveal Hemodynamics Associated with Diabetic Retinopathy with Adaptive Optics Scanning Laser Ophthalmoscopy and Computational Fluid Dynamics SO 2015 37TH 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 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) CY AUG 25-29, 2015 CL Milan, ITALY ID HUMANS AB Diabetic retinopathy (DR) remains the leading cause of visual loss in working age adults in the United States and other developed countries worldwide. Previous studies have reported hemodynamic changes in the diabetic eye that precede clinically evident pathological alterations of the retinal microvasculature. There exists a pressing need for new methods to allow greater understanding of these early hemodynamic changes that occur in DR. In the current study, we propose a noninvasive method for the assessment of hemodynamics around the fovea (a region of the eye of paramount importance for vision). The proposed methodology combines adaptive optics scanning laser ophthalmoscopy and computational fluid dynamics modeling and simulation. Our preliminary results indicate that the technique presented here is feasible for the assessment of hemodynamics in the foveal region of the eye and, moreover, that it is capable of detecting differences in hemodynamics between eyes that may be associated with DR status. We believe that the proposed methodology has the potential to become a useful tool for the evaluation of human retinal hemodynamics in a clinical context. C1 [Bernabeu, Miguel O.; Coveney, Peter V.] UCL, Ctr Computat Sci, Mortimer St, London WC1E 6BT, England. [Lu, Yang; Aiello, Lloyd P.; Sun, Jennifer K.] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. [Lammer, Jan] Med Univ Vienna, Vienna, Austria. [Aiello, Lloyd P.; Sun, Jennifer K.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02215 USA. RP Bernabeu, MO (reprint author), Univ Edinburgh, Coll Med & Vet Med, Usher Inst, Med Informat Ctr, Edinburgh EH16 4TJ, Midlothian, Scotland. EM miguel.bernabeu@ed.ac.uk; yang.lu@joslin.harvard.edu; jan.lammer@meduniwien.ac.at; lloydpaul.aiello@joslin.harvard.edu; p.v.coveney@ucl.ac.uk; jennifer.sun@joslin.harvard.edu NR 13 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-9270-1 J9 IEEE ENG MED BIO PY 2015 BP 8070 EP 8073 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BE4HD UT WOS:000371717208086 ER PT S AU Lee, SI Daneault, JF Golabchi, FN Patel, S Paganoni, S Shih, L Bonato, P AF Lee, Sunghoon Ivan Daneault, Jean-Francois Golabchi, Fatemeh Noushin Patel, Shyamal Paganoni, Sabrina Shih, Ludy Bonato, Paolo GP IEEE TI A Novel Method for Assessing the Severity of Levodopa-Induced Dyskinesia using Wearable Sensors SO 2015 37TH 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 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) CY AUG 25-29, 2015 CL Milan, ITALY AB Patients with Parkinson's disease often experience significant changes in the severity of dyskinesia when they undergo titration of their medications. Dyskinesia is marked by involuntary jerking movements that occur randomly in a burst-like fashion. The burst-like nature of such movements makes it difficult to estimate the clinical scores of severity of dyskinesia using wearable sensors. Clinical observations are generally made over intervals of 15-30 s. On the other hand, techniques designed to estimate the severity of dyskinesia based on the analysis of wearable sensor data typically use data segments of approximately 5 s. Consequently, some data segments might include dyskinetic movements, whereas others might not. Herein, we propose a novel method suitable to automatically select data segments from the training dataset that are marked by dyskinetic movements. The proposed method also aggregates results derived from the testing dataset using a machine learning algorithm to estimate the severity of dyskinesia from wearable sensor data. Results obtained from the analysis of sensor data collected from seven subjects with Parkinson's disease showed a marked improvement in the accuracy of the estimation of clinical scores of dyskinesia. C1 [Lee, Sunghoon Ivan; Daneault, Jean-Francois; Golabchi, Fatemeh Noushin; Patel, Shyamal; Paganoni, Sabrina; Bonato, Paolo] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA 02114 USA. [Shih, Ludy] BIDMC, Dept Neurol, Boston, MA 02215 USA. RP Lee, SI (reprint author), Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA 02114 USA. EM slee117@partners.org; jdaneault@partners.org; fgolabchi@partners.org; spatel19@partners.org; spaganoni@partners.org; lshih@caregroup.harvard.edu; pbonato@partners.org NR 12 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 978-1-4244-9270-1 J9 IEEE ENG MED BIO PY 2015 BP 8087 EP 8090 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BE4HD UT WOS:000371717208090 ER PT S AU Schopfer, DW Khera, A Levine, B Forman, DE AF Schopfer, David W. Khera, Amit Levine, Benjamin Forman, Daniel E. BE Willerson, JT Holmes, DR TI Preventive Cardiology: The Effects of Exercise SO CORONARY ARTERY DISEASE SE Cardiovascular Medicine-London LA English DT Article; Book Chapter DE Exercise training; Exercise prescription; Physical activity; Physical fitness; Cardiac Rehabilitation; Habitual exercise; Sleep; Secondary prevention; Risk Factor Modification; Central exercise effects; Peripheral exercise effects; Skeletal muscle; Vascular; Autonomic function; Coagulation; Heart failure ID CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; ACUTE MYOCARDIAL-INFARCTION; TIME PHYSICAL-ACTIVITY; SUDDEN CARDIAC DEATH; RANDOMIZED CONTROLLED-TRIAL; MIDDLE-AGED MEN; HEALTH-CARE PROFESSIONALS; QUALITY-OF-LIFE; PRESERVED EJECTION FRACTION AB Physical adaptations to dynamic exercise (i. e., exercise training) lead to increased aerobic and strength capacities (including cardiovascular reserve, endurance and velocity of movement) (Noakes et al., Clin Sports Med 3(2): 527-543, 1984). These attributes are relevant in vigorous athletes, who in addition to high performance also tend to have better metabolism and health, as well as for older adults who compared to age-matched sedentary adults enjoy better health, greater independence, and better quality of life. Exercise regimens are best tailored to the needs of individual patients, with varying emphasis on strength vs. aerobic, and with different intensities/modes based on clinical contexts. Since the 1950s, an extensive literature has described the benefits and risks of exercise, including reports by the American Heart Association (Fletcher et al., Circulation 86(1): 340-344, 1992) and the International Society and Federation of Cardiology (Bijnen et al., J Int Soc Federation Cardiol 2: 5-6, 1992). The aggregate data conveys a strong case that a sedentary lifestyle is detrimental to health, and creates high a risk for cardiovascular disease. The weight of evidence even led to a Surgeon General's report which made clear and explicit recommendations regarding physical activity (Department of Health and Human Services. Physical activity and health: a report of the Surgeon General. Atlanta: National Center for Chronic Disease Prevention and Health Promotion; 1996). Several major agencies and organizations including the National Institutes of Health, the Centers for Disease Control and Prevention, the American College of Sports Medicine, and the American Heart Association have advanced related recommendations that all adults should exercise with moderate-intensity for at least 30 min on most and preferably all day of the week (Department of Health and Human Services. Physical activity and health: a report of the Surgeon General. Atlanta: National Center for Chronic Disease Prevention and Health Promotion; 1996; Physical activity and cardiovascular health. NIH Consensus Development Panel on Physical Activity and Cardiovascular Health JAMA 276(3): 241-246, 1996; Pate et al., JAMA 273(5): 402-407, 1995; Thompson et al. Circulation 107(24): 3109-3116, 2003). Nonetheless, the majority of adults do not attain the recommended levels of exercise and they are not routinely counseled on the important health benefits of regular physical activity (Prevalence of physical activity, including lifestyle activities among adults - United States, 2000-2001 MMWR Morb Mortal Wkly Rep 52(32): 764-769, 2003; Wee et al., JAMA 282(16): 1583-1588, 1999). This chapter explores the role of occupational and recreational physical activity on morbidity and mortality from coronary heart disease (CHD). The first section will focus on healthy individuals, i. e., primary prevention, and will discuss epidemiologic evidence supporting the practice of regular exercise. The second section will discuss secondary prevention, for patients who already have had some manifestation of CHD such as angina pectoris or myocardial infarction or who have undergone revascularization. Finally, the third section will provide a pathophysiologic framework of the possible mechanisms for the beneficial effects of exercise training. Physical activity, exercise training, and physical fitness have distinct definitions (Thompson et al., Circulation 107(24): 3109-3116, 2003; Caspersen et al., Public Health Rep 100(2): 126-131, 1985). Physical activity is any bodily movement produced by skeletal muscles that results in energy expenditure, including occupational, athletic, and other activities. Exercise training refers more specifically to activity that is planned, structured, and purposeful with the intent of developing or maintaining physical fitness (Caspersen et al., Public Health Rep 100(2): 126-131, 1985). Physical fitness is a set of measurable health-related attributes, including muscle strength, flexibility, body composition, and cardiorespiratory power and endurance. While all are important facets of health, only a minority of adults of any age meet current recommendations for physical activity, exercise training, and/or achieve "optimal" physical fitness (Hansen et al., Med Sci Sports Exerc 44(2): 266-272, 2012). In this chapter, we initially focus on the distinctive health benefits of endurance and strength exercise training. Endurance or "aerobic" exercise includes activities with energy demands that are met primarily by oxidative metabolism. Strength exercise is specialized to increase muscle mass and anaerobic endurance. Strength training also can facilitate aerobic performance as it has the potential to moderate muscle atrophy (sarcopenia) that otherwise occurs with aging, deconditioning, and multimorbidity. Increasing muscle mass with strength training also has benefit of increasing weight loss by raising metabolism and caloric expenditure. Therefore, the combination of aerobic and strength training is often optimal, especially for achieving fitness goals of elderly, obese and/or deconditioned adults who benefit particularly from increased muscle mass as well as aerobic training effects (Brown and Holloszy Aging (Milano) 5(6): 427-434, 1993; McAuley J Behav Med 16(1): 103-113, 1993). While there is conceptually value for exercise regimens that are longer and more intense, this is often not feasible for adults who are frail, deconditioned, or those who may simply be averse to exercise. However, even small amounts of exercise have value; research shows that as little as 15 min of low intensity exercise may be beneficial (Wen et al., Lancet 378(9798): 1244-1253, 2011). Therefore, doing any exercise is better than no exercise, particularly because exercise-induced strength and aerobic capacities often facilitate greater physical activity in addition to exercise. C1 [Schopfer, David W.] San Francisco VA Med Ctr, Dept Med, Div Cardiol, San Francisco, CA USA. [Khera, Amit] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Cardiol, Dallas, TX 75390 USA. [Levine, Benjamin] Texas Hlth Presbyterian, Inst Exercise & Environm Med, S Finley Ewing Jr Chair Wellness, Dallas, TX USA. [Levine, Benjamin] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Cardiol, Cardiovasc Res, Dallas, TX 75390 USA. [Levine, Benjamin] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Cardiol, Med & Cardiol, Dallas, TX 75390 USA. [Levine, Benjamin] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Cardiol, Exercise Sci, Dallas, TX 75390 USA. [Forman, Daniel E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med,Dept Med, Boston, MA 02115 USA. [Forman, Daniel E.] VA Boston Med Ctr, Dept Med, Cardiol Sect, Boston, MA USA. RP Forman, DE (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med,Dept Med, Boston, MA 02115 USA. EM deforman@partners.org NR 364 TC 0 Z9 0 U1 2 U2 4 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL RD FARNCOMBE, GODALMING GU7 1NH, SURREY, ENGLAND SN 2363-5061 BN 978-1-4471-2828-1; 978-1-4471-2827-4 J9 CARDIOVASC MED-LOND PY 2015 BP 737 EP 766 DI 10.1007/978-1-4471-2828-1_28 D2 10.1007/978-1-4471-2828-1 PG 30 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA BE2UY UT WOS:000370136700029 ER PT J AU Sharbaugh, T van Zijl, K Beauchemin, E Boland, C AF Sharbaugh, Tracy van Zijl, Karen Beauchemin, Emily Boland, Catherine TI Paediatric radiology from a psychosocial lens SO SA JOURNAL OF RADIOLOGY LA English DT Review ID AGGRESSION AB Globally, hospitals and medical centres have a reputation of causing individual patients an increased level of anxiety, stress and pain owing to their foreign environments, intimidating examinations and rigorous treatments. Because of children's cognitive and developmental levels of understanding and communication, they are more susceptible to increased levels of stress and trauma associated with medical examinations and hospitalisation. Certified Child Life Specialists (CCLSs) are professionals trained in child development and family systems expertise who work directly with children and families to meet their psychosocial and emotional needs in order to help them overcome some of life's most challenging events, including hospitalisation, illness and trauma. This article aims to address the history of the child life profession and the significance of child life in a paediatric imaging unit, and to discuss the current and future status of psychosocial services in South Africa. C1 [Sharbaugh, Tracy] Massachusetts Gen Hosp, Boston Childrens Hosp, Boston, MA 02114 USA. [van Zijl, Karen] OPSSA, Johannesburg, South Africa. [Beauchemin, Emily] Levine Childrens Hosp, Carolinas HealthCare Syst, Charlotte, NC USA. [Boland, Catherine] Univ Calif, Global Hlth Sci, Berkeley, CA USA. RP Sharbaugh, T (reprint author), 1333 Via Isidro Oceanside, Oceanside, CA 92056 USA. EM tracylsharbaugh@gmail.com NR 10 TC 0 Z9 0 U1 1 U2 1 PU AOSIS OPEN JOURNALS PI CAPE TOWN PA POSTNET SUITE 55, PRIVATE BAG X22, TYGERVALLEY, CAPE TOWN, 00000, SOUTH AFRICA SN 1027-202X EI 2078-6778 J9 SA J RADIOL JI SA J. Radiol. PY 2015 VL 19 IS 2 AR 913 DI 10.4102/sajr.v19i2.913 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DH1EH UT WOS:000372526700014 ER PT S AU Jacob, T Snyder, W AF Jacob, Theju Snyder, Wesley GP IEEE TI Learning Rule for Associative Memory in Recurrent Neural Networks SO 2015 INTERNATIONAL JOINT CONFERENCE ON NEURAL NETWORKS (IJCNN) SE IEEE International Joint Conference on Neural Networks (IJCNN) LA English DT Proceedings Paper CT International Joint Conference on Neural Networks (IJCNN) CY JUL 12-17, 2015 CL Killarney, IRELAND AB We present a new learning rule for intralayer connections in neural networks. The rule is based on Hebbian learning principles and is derived from information theoretic considerations. A simple network trained using the rule is shown to have associative memory like properties. The network acts by building connections between correlated data points, under constraints. C1 [Jacob, Theju; Snyder, Wesley] N Carolina State Univ, Dept Elect & Comp Engn, Raleigh, NC 27695 USA. RP Jacob, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. EM theju.jacob@gmail.com; wes@ncsu.edu NR 17 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2161-4393 BN 978-1-4799-1959-8 J9 IEEE IJCNN PY 2015 PG 5 WC Computer Science, Artificial Intelligence; Computer Science, Hardware & Architecture; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BE3HR UT WOS:000370730601103 ER PT S AU Allen, JB Nakajima, HH Maoileidigh, DO AF Allen, Jont B. Nakajima, Hideko Heidi Maoileidigh, Daibhid O. BE Karavitaki, KD Corey, DP TI Middle Ear Mechanics and Progress in Cochlear Modeling: A Moderated Discussion SO MECHANICS OF HEARING: PROTEIN TO PERCEPTION SE AIP Conference Proceedings LA English DT Proceedings Paper CT 12th International Workshop on the Mechanics of Hearing CY JUN 23-29, 2014 CL Cape Sounio, GREECE AB The following is an edited transcript of a recorded discussion session on the topics of "Middle Ear Mechanics" and "Progress in Cochlear Modeling". The discussion, moderated by the authors, took place at the 12th International Workshop on the Mechanics of Hearing held at Cape Sounio, Greece, in June 2014. All participants knew that the session was being recorded. In view of both the spontaneous nature of the discussion and the editing, however, this transcript may not represent the considered or final views of the participants, and may not represent a consensus of experts in the field. The reader is advised to consult additional independent publications. C1 [Allen, Jont B.] Univ Illinois, Beckman Inst, Dept Comp & Elect Engn, Urbana, IL 61801 USA. [Nakajima, Hideko Heidi] Harvard Univ, Sch Med, Boston, MA USA. [Nakajima, Hideko Heidi] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Maoileidigh, Daibhid O.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. [Maoileidigh, Daibhid O.] Rockefeller Univ, Lab Sensory Neurosci, New York, NY 10021 USA. RP Allen, JB (reprint author), Univ Illinois, Beckman Inst, Dept Comp & Elect Engn, Urbana, IL 61801 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-1350-4 J9 AIP CONF PROC PY 2015 VL 1703 AR 060007 DI 10.1063/1.4939362 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Otorhinolaryngology SC Biochemistry & Molecular Biology; Biophysics; Otorhinolaryngology GA BE4PY UT WOS:000372065400049 ER PT S AU Arnold, A Stieger, C Caversaccio, M Kompis, M Guignard, J AF Arnold, Andreas Stieger, Christof Caversaccio, Marco Kompis, Martin Guignard, Jeremie BE Karavitaki, KD Corey, DP TI Bone Conduction Responses of Middle Ear Structures in Thiel Embalmed Heads SO MECHANICS OF HEARING: PROTEIN TO PERCEPTION SE AIP Conference Proceedings LA English DT Proceedings Paper CT 12th International Workshop on the Mechanics of Hearing CY JUN 23-29, 2014 CL Cape Sounio, GREECE ID CADAVER HEADS; TRANSMISSION; SOUND AB Thiel-embalmed human whole-head specimens offer a promising alternative model for bone conduction (BC) studies of middle ear structures. In this work we present the Thiel model's linearity and stability over time as well as its possible use in the study of a fixed ossicle chain. Using laser Doppler vibrometry (LDV), the motion of the retroauricular skull, the promontory, the stapes footplate and the round window (RW) were measured. A bone-anchored hearing aid stimulated the ears with step sinus tones logarithmically spread between 0.1 and 10 kHz. Linearity of the model was verified using input levels in steps of 10 dBV. The stability of the Thiel model over time was examined with measurements repeated after hours and weeks. The influence of a cement-fixed stapes was assessed. The middle ear elements measured responded linearly in amplitude for the applied input levels (100, 32.6, and 10 mV). The variability of measurements for both short-(2 h) and long-term (4-16 weeks) repetitions in the same ear was lower than the interindividual difference. The fixation of the stapes induced a lowered RW displacement for frequencies near 750 Hz (-4 dB) and an increased displacement for frequencies above 1 kHz (max. +3.7 dB at 4 kHz). LDV assessment of BC-induced middle ear motion in Thiel heads can be performed with stable results. The vibratory RW response is affected by the fixation of the stapes, indicating a measurable effect of ossicle chain inertia on BC response in Thiel embalmed heads. C1 [Arnold, Andreas; Caversaccio, Marco; Kompis, Martin] Univ Bern, Inselspital, Dept ENT, CH-3010 Bern, Switzerland. [Arnold, Andreas; Stieger, Christof; Caversaccio, Marco; Guignard, Jeremie] Univ Bern, ARTORG Ctr, CH-3010 Bern, Switzerland. [Stieger, Christof] Univ Basel Hosp, Dept Otorhinolaryngol, CH-4031 Basel, Switzerland. [Guignard, Jeremie] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Eaton Peabody Lab, Boston, MA USA. RP Arnold, A (reprint author), Univ Bern, Inselspital, Dept ENT, CH-3010 Bern, Switzerland. NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-1350-4 J9 AIP CONF PROC PY 2015 VL 1703 AR 060013 DI 10.1063/1.4939368 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Otorhinolaryngology SC Biochemistry & Molecular Biology; Biophysics; Otorhinolaryngology GA BE4PY UT WOS:000372065400055 ER PT S AU Berezina-Greene, MA Guinan, JJ AF Berezina-Greene, Maria A. Guinan, John J., Jr. BE Karavitaki, KD Corey, DP TI Time-Frequency Analysis of Stimulus Frequency Otoacoustic Emissions and Their Changes with Efferent Stimulation in Guinea Pigs SO MECHANICS OF HEARING: PROTEIN TO PERCEPTION SE AIP Conference Proceedings LA English DT Proceedings Paper CT 12th International Workshop on the Mechanics of Hearing CY JUN 23-29, 2014 CL Cape Sounio, GREECE ID COHERENT REFLECTION; LATENCY COMPONENTS; COCHLEAR MODEL; RESPONSES; ORIGIN; DELAYS AB To aid in understanding their origin, stimulus frequency otoacoustic emissions (SFOAEs) were measured at a series of tone frequencies using the suppression method, both with and without stimulation of medial olivocochlear (MOC) efferents, in anesthetized guinea pigs. Time-frequency analysis showed SFOAE energy peaks in 1-3 delay components throughout the measured frequency range (0.5-12 kHz). One component's delay usually coincided with the phase-gradient delay. When multiple delay components were present, they were usually near SFOAE dips. Below 2 kHz, SFOAE delays were shorter than predicted from mechanical measurements. With MOC stimulation, SFOAE amplitude was decreased at most frequencies, but was sometimes enhanced, and all SFOAE delay components were affected. The MOC effects and an analysis of model data suggest that the multiple SFOAE delay components arise at the edges of the traveling-wave peak, not far basal of the peak. Comparisons with published guinea-pig neural data suggest that the short latencies of low-frequency SFOAEs may arise from coherent reflection from an organ-of-Corti motion that has a shorter group delay than the traveling wave. C1 [Berezina-Greene, Maria A.; Guinan, John J., Jr.] Harvard MIT Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA USA. [Berezina-Greene, Maria A.; Guinan, John J., Jr.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. [Guinan, John J., Jr.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Berezina-Greene, MA (reprint author), Harvard MIT Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-1350-4 J9 AIP CONF PROC PY 2015 VL 1703 AR 090006 DI 10.1063/1.4939404 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Otorhinolaryngology SC Biochemistry & Molecular Biology; Biophysics; Otorhinolaryngology GA BE4PY UT WOS:000372065400091 ER PT S AU Fridberger, A Guinan, JJ AF Fridberger, Anders Guinan, John J., Jr. BE Karavitaki, KD Corey, DP TI What Shapes the Stimulus to the Inner Hair Cell?: A Moderated Discussion SO MECHANICS OF HEARING: PROTEIN TO PERCEPTION SE AIP Conference Proceedings LA English DT Proceedings Paper CT 12th International Workshop on the Mechanics of Hearing CY JUN 23-29, 2014 CL Cape Sounio, GREECE AB The following is an edited transcript of a recorded discussion session on the topic of "What Shapes the Stimulus to the Inner Hair Cell?". The discussion, moderated by the authors, took place at the 12th International Workshop on the Mechanics of Hearing held at Cape Sounio, Greece, in June 2014. All participants knew that the session was being recorded. In view of both the spontaneous nature of the discussion and the editing, however, this transcript may not represent the considered or final views of the participants, and may not represent a consensus of experts in the field. The reader is advised to consult additional independent publications. C1 [Fridberger, Anders] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Fridberger, Anders] Linkoping Univ, Linkoping, Sweden. [Guinan, John J., Jr.] Harvard MIT Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA USA. [Guinan, John J., Jr.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. [Guinan, John J., Jr.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Fridberger, A (reprint author), Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-1350-4 J9 AIP CONF PROC PY 2015 VL 1703 AR 080006 DI 10.1063/1.4939397 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Otorhinolaryngology SC Biochemistry & Molecular Biology; Biophysics; Otorhinolaryngology GA BE4PY UT WOS:000372065400084 ER PT S AU Guignard, J Cheng, JT Ravicz, ME Rosowski, JJ AF Guignard, Jeremie Cheng, Jeffrey T. Ravicz, Michael E. Rosowski, John J. BE Karavitaki, KD Corey, DP TI Dynamics of the Tympanic Membrane: Multiple-Specimen Study of Digital Holograms SO MECHANICS OF HEARING: PROTEIN TO PERCEPTION SE AIP Conference Proceedings LA English DT Proceedings Paper CT 12th International Workshop on the Mechanics of Hearing CY JUN 23-29, 2014 CL Cape Sounio, GREECE ID MOTION; FIELD AB Stroboscopic digital holography has been used to measure sound-induced tympanic membrane (TM) surface motion with a high spatial resolution. In the current state of the art, holograms from different specimens can be compared qualitatively by inspection and quantitatively by manual identification of regions of interest. However, anatomical variations in the shape of the TM and geometrical variations due to changes in relative position and orientation of the specimen with respect to the camera preclude point-by-point metrics across specimens. The aim of this study is to create a set of shape-normalized TM motion maps in order to quantify the average motion and variability in a set of specimens. We present a method in which the motion maps of 5 cadaveric human TMs were rotated, translated, scaled and sheared to normalize TM orientation, size, and position, and we show preliminary results of cross-specimen analysis of motion. C1 [Guignard, Jeremie] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Eaton Peabody Lab, Boston, MA USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Guignard, J (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Eaton Peabody Lab, Boston, MA USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-1350-4 J9 AIP CONF PROC PY 2015 VL 1703 AR 060009 DI 10.1063/1.4939364 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Otorhinolaryngology SC Biochemistry & Molecular Biology; Biophysics; Otorhinolaryngology GA BE4PY UT WOS:000372065400051 ER PT S AU Koussa, MA Sotomayor, M Wong, WP Corey, DP AF Koussa, Mounir A. Sotomayor, Marcos Wong, Wesley P. Corey, David P. BE Karavitaki, KD Corey, DP TI Towards Force Spectroscopy of Single Tip-Link Bonds SO MECHANICS OF HEARING: PROTEIN TO PERCEPTION SE AIP Conference Proceedings LA English DT Proceedings Paper CT 12th International Workshop on the Mechanics of Hearing CY JUN 23-29, 2014 CL Cape Sounio, GREECE ID SENSORY HAIR-CELLS; MOLECULAR-DYNAMICS; TRANSDUCTION; MECHANOTRANSDUCTION; PROTOCADHERIN-15; CADHERIN-23; MECHANICS; INNER AB Inner-ear mechanotransduction relies on tip links, fine protein filaments made of cadherin-23 and protocadherin-15 that convey tension to mechanosensitive channels at the tips of hair-cell stereocilia. The tip-link cadherins are thought to form a heterotetrameric complex, with two cadherin-23 molecules forming the upper part of the filament and two protocadherin-15 molecules forming the lower end. The interaction between cadherin-23 and protocadherin-15 is mediated by their N-terminal tips. Missense mutations that modify the interaction interface impair binding and lead to deafness. Molecular dynamics simulations predict that the tip-link bond is mechanically strong enough to withstand forces in hair cells, but its experimentally determined strength is unknown. We have developed molecular tools to facilitate single-molecule force spectroscopy on the tip link bond. Self-assembling DNA nanoswitches are functionalized with the interacting tips of cadherin-23 and protocadherin-15 using the enzyme sortase under conditions that preserve protein function. These tip link nanoswitches are designed to provide a signature force-extension profile. This molecular signature should allow us to identify single-molecule rupture events in pulling experiments. C1 [Koussa, Mounir A.] Harvard Univ, Sch Med, Dept Neurobiol, Program Neurosci, Boston, MA 02115 USA. [Sotomayor, Marcos] Ohio State Univ, Dept Chem & Biochem, Columbus, OH 43210 USA. [Wong, Wesley P.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Wong, Wesley P.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Wong, Wesley P.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Corey, David P.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Corey, David P.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Koussa, MA (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, Program Neurosci, Boston, MA 02115 USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-1350-4 J9 AIP CONF PROC PY 2015 VL 1703 AR 030002 DI 10.1063/1.4939317 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Otorhinolaryngology SC Biochemistry & Molecular Biology; Biophysics; Otorhinolaryngology GA BE4PY UT WOS:000372065400004 ER PT S AU Lichtenhan, JT Salt, AN Guinan, JJ AF Lichtenhan, Jeffery T. Salt, Alec N. Guinan, John J., Jr. BE Karavitaki, KD Corey, DP TI The Auditory Nerve Overlapped Waveform (ANOW): A New Objective Measure of Low-Frequency Hearing SO MECHANICS OF HEARING: PROTEIN TO PERCEPTION SE AIP Conference Proceedings LA English DT Proceedings Paper CT 12th International Workshop on the Mechanics of Hearing CY JUN 23-29, 2014 CL Cape Sounio, GREECE ID GUINEA-PIG; INNER-EAR; HYDROPS; TONES; CHINCHILLA; COCHLEA AB One of the most pressing problems today in the mechanics of hearing is to understand the mechanical motions in the apical half of the cochlea. Almost all available measurements from the cochlear apex of basilar membrane or other organ-of-Corti transverse motion have been made from ears where the health, or sensitivity, in the apical half of the cochlea was not known. A key step in understanding the mechanics of the cochlear base was to trust mechanical measurements only when objective measures from auditory-nerve compound action potentials (CAPs) showed good preparation sensitivity. However, such traditional objective measures are not adequate monitors of cochlear health in the very low-frequency regions of the apex that are accessible for mechanical measurements. To address this problem, we developed the Auditory Nerve Overlapped Waveform (ANOW) that originates from auditory nerve output in the apex. When responses from the round window to alternating low-frequency tones are averaged, the cochlear microphonic is canceled and phase-locked neural firing interleaves in time (i.e., overlaps). The result is a waveform that oscillates at twice the probe frequency. We have demonstrated that this Auditory Nerve Overlapped Waveform - called ANOW - originates from auditory nerve fibers in the cochlear apex [8], relates well to single-auditory-nerve-fiber thresholds, and can provide an objective estimate of low-frequency sensitivity [7]. Our new experiments demonstrate that ANOW is a highly sensitive indicator of apical cochlear function. During four different manipulations to the scala media along the cochlear spiral, ANOW amplitude changed when either no, or only small, changes occurred in CAP thresholds. Overall, our results demonstrate that ANOW can be used to monitor cochlear sensitivity of low-frequency regions during experiments that make apical basilar membrane motion measurements. C1 [Lichtenhan, Jeffery T.; Salt, Alec N.] Washington Univ, Sch Med, Dept Otolaryngol, St Louis, MO 63110 USA. [Guinan, John J., Jr.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. [Guinan, John J., Jr.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Lichtenhan, JT (reprint author), Washington Univ, Sch Med, Dept Otolaryngol, St Louis, MO 63110 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-1350-4 J9 AIP CONF PROC PY 2015 VL 1703 AR 040008 DI 10.1063/1.4939342 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Otorhinolaryngology SC Biochemistry & Molecular Biology; Biophysics; Otorhinolaryngology GA BE4PY UT WOS:000372065400029 ER PT S AU Merchant, GR Siegel, JH Neely, ST Rosowski, JJ Nakajima, HH AF Merchant, Gabrielle R. Siegel, Jonathan H. Neely, Stephen T. Rosowski, John J. Nakajima, Hideko H. BE Karavitaki, KD Corey, DP TI Effect of Middle-Ear Pathology on High-Frequency Ear-Canal Reflectance Measurements in the Frequency and Time Domains SO MECHANICS OF HEARING: PROTEIN TO PERCEPTION SE AIP Conference Proceedings LA English DT Proceedings Paper CT 12th International Workshop on the Mechanics of Hearing CY JUN 23-29, 2014 CL Cape Sounio, GREECE ID UMBO VELOCITY; DISORDERS; ADULTS AB Wideband immittance and reflectance have not been well described at frequencies above 6-8 kHz, and past analyses of these measurements have focused on the responses to stimulus frequencies below 3-4 kHz, while ignoring high-frequency or time-domain information. This work uses a novel approach to measure reflectance that utilizes high-frequency signals and analyzes reflectance in both the frequency and the time domains. Experiments were performed with fresh normal human temporal bones before and after simulating various middle-ear pathologies. In addition to experimental data, novel model analyses were used to obtain fitted parameter values of middle-ear elements that vary systematically due to simulations and thus may have diagnostic implications. Our results show that high-frequency measurements improve temporal resolution of reflectance measurements, and this data combined with novel modeling techniques provides separation of three major conductive pathologies. C1 [Merchant, Gabrielle R.] Harvard MIT Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol, Cambridge, MA USA. [Merchant, Gabrielle R.; Rosowski, John J.; Nakajima, Hideko H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. [Siegel, Jonathan H.] Northwestern Univ, Knowles Hearing Ctr, Roxelyn & Richard Pepper Dept Commun Sci & Disord, Evanston, IL USA. [Neely, Stephen T.] Boys Town Natl Res Hosp, Omaha, NE 68131 USA. RP Merchant, GR (reprint author), Harvard MIT Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol, Cambridge, MA USA. OI Merchant, Gabrielle/0000-0001-7251-1879 NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-1350-4 J9 AIP CONF PROC PY 2015 VL 1703 AR 060003 DI 10.1063/1.4939358 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Otorhinolaryngology SC Biochemistry & Molecular Biology; Biophysics; Otorhinolaryngology GA BE4PY UT WOS:000372065400045 ER PT S AU Stieger, C Farahmand, RB Page, BF Roushan, K Merchant, JP Abur, D Rosowski, JJ Nakajima, HH AF Stieger, Christof Farahmand, Rosemary B. Page, Brent F. Roushan, Kourosh Merchant, Julie P. Abur, Defne Rosowski, John J. Nakajima, Hideko Heidi BE Karavitaki, KD Corey, DP TI Pressures in the Human Cochlea During Bone Conduction SO MECHANICS OF HEARING: PROTEIN TO PERCEPTION SE AIP Conference Proceedings LA English DT Proceedings Paper CT 12th International Workshop on the Mechanics of Hearing CY JUN 23-29, 2014 CL Cape Sounio, GREECE AB The mechanisms of bone conduction (BC) hearing, which is important in diagnosis and treatment of hearing loss, are poorly understood, thus limiting use of BC. Recently, information gained by intracochlear pressure measurements has revealed that the mechanisms of sound transmission that drive pressure differences across the cochlear partition are different for air conduction (AC) than for round-window stimulation. Presently we are utilizing these pressure measurement techniques in fresh human cadaveric preparations to improve our understanding of sound transmission during BC. We have modified our technique of intracochlear pressure measurements for the special requirements of studying BC, as bone vibration poses challenges for making these measurements. Fiberoptic pressure sensors were inserted through cochleostomies in both scalae at the base of the cochlea. The cochleostomies were then tightly sealed with the sensors in place to prevent air and fluid leaks, and the sensors were firmly secured to ensure uniform vibrations of the sensors and surrounding bone of the cochlea. The velocity of the stapes, round window and cochlear promontory were each measured with laser Doppler vibrometry simultaneous to the intracochlear pressure measurements. To understand the contribution of middle-ear inertia, the incudo-stapedial joint was severed. Subsequently, the stapes footplate was fixed (similar to the consequence of otosclerosis) to determine the effect of removing the mobility of the oval window. BC stimulation resulted in pressure in scala vestibuli that was significantly higher than in scala tympani, such that the differential pressure across the partition - the cochlear drive input - was similar to scala vestibuli pressure (and overall, similar to the relationship found during AC but different than during round-window stimulation). After removing the inertial mass of the middle ear, with only the stapes attached to the flexible oval window, all pressures dropped similarly (10 dB). Fixing the oval window resulted in further drop of all pressures (10 dB more). These decreases in pressure occurred around 1-4 kHz, consistent with clinical observations of Carhart's notch. C1 [Stieger, Christof; Roushan, Kourosh] Univ Basel Hosp, CH-4031 Basel, Switzerland. [Stieger, Christof] Univ Bern, Bern, Switzerland. [Farahmand, Rosemary B.; Rosowski, John J.; Nakajima, Hideko Heidi] Harvard Univ, Sch Med, Boston, MA USA. [Farahmand, Rosemary B.; Page, Brent F.; Merchant, Julie P.; Abur, Defne; Rosowski, John J.; Nakajima, Hideko Heidi] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Stieger, C (reprint author), Univ Basel Hosp, CH-4031 Basel, Switzerland. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-1350-4 J9 AIP CONF PROC PY 2015 VL 1703 AR 060004 DI 10.1063/1.4939359 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Otorhinolaryngology SC Biochemistry & Molecular Biology; Biophysics; Otorhinolaryngology GA BE4PY UT WOS:000372065400046 ER PT S AU Li, JF Zhang, DD Sheen, J AF Li, Jian-Feng Zhang, Dandan Sheen, Jen BE Alonso, JM Stepanova, AN TI Targeted Plant Genome Editing via the CRISPR/Cas9 Technology SO PLANT FUNCTIONAL GENOMICS: METHODS AND PROTOCOLS, 2ND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Plant genome editing; CRISPR/Cas9; Protoplast transient expression assay; Chromosomal mutagenesis; Homologous recombination ID ARABIDOPSIS-THALIANA; GUIDE RNA; GENE; DNA; ENDONUCLEASE; MUTAGENESIS; NUCLEASES; CAS9; ZFN AB Targeted modification of plant genome is key for elucidating and manipulating gene functions in basic and applied plant research. The CRISPR (clustered regularly interspaced short palindromic repeats)/CRISPR-associated protein (Cas) technology is emerging as a powerful genome editing tool in diverse organisms. This technology utilizes an easily reprogrammable guide RNA (gRNA) to guide Streptococcus pyogenes Cas9 endonuclease to generate a DNA double-strand break (DSB) within an intended genomic sequence and subsequently stimulate chromosomal mutagenesis or homologous recombination near the DSB site through cellular DNA repair machineries. In this chapter, we describe the detailed procedure to design, construct, and evaluate dual gRNAs for plant codon-optimized Cas9 (pcoCas9)-mediated genome editing using Arabidopsis thaliana and Nicotiana benthamiana protoplasts as model cellular systems. We also discuss strategies to apply the CRISPR/Cas9 system to generating targeted genome modifications in whole plants. C1 [Li, Jian-Feng; Zhang, Dandan; Sheen, Jen] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Li, JF (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. FU NIGMS NIH HHS [R01 GM70567, R01 GM60493, R01 GM060493] NR 14 TC 6 Z9 10 U1 10 U2 39 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-2444-8; 978-1-4939-2443-1 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1284 BP 239 EP 255 DI 10.1007/978-1-4939-2444-8_12 D2 10.1007/978-1-4939-2444-8 PG 17 WC Plant Sciences SC Plant Sciences GA BE5ET UT WOS:000372659000013 PM 25757776 ER PT J AU Bauserman, M Lokangaka, A Thorsten, V Tshefu, A Goudar, SS Esamai, F Garces, A Saleem, S Pasha, O Patel, A Manasyan, A Berrueta, M Kodkany, B Chomba, E Liechty, EA Hambidge, KM Krebs, NF Derman, RJ Hibberd, PL Althabe, F Carlo, WA Koso-Thomas, M Goldenberg, RL Wallace, DD McClure, EM Bose, CL AF Bauserman, Melissa Lokangaka, Adrien Thorsten, Vanessa Tshefu, Antoinette Goudar, Shivaprasad S. Esamai, Fabian Garces, Ana Saleem, Sarah Pasha, Omrana Patel, Archana Manasyan, Albert Berrueta, Mabel Kodkany, Bhala Chomba, Elwyn Liechty, Edward A. Hambidge, K. Michael Krebs, Nancy F. Derman, Richard J. Hibberd, Patricia L. Althabe, Fernando Carlo, Waldemar A. Koso-Thomas, Marion Goldenberg, Robert L. Wallace, Dennis D. McClure, Elizabeth M. Bose, Carl L. TI Risk factors for maternal death and trends in maternal mortality in low- and middle-income countries: a prospective longitudinal cohort analysis SO REPRODUCTIVE HEALTH LA English DT Article ID SYSTEMATIC ANALYSIS; NEWBORN; SURVEILLANCE; HEALTH; CARE AB Background: Because large, prospective, population-based data sets describing maternal outcomes are typically not available in low-and middle-income countries, it is difficult to monitor maternal mortality rates over time and to identify factors associated with maternal mortality. Early identification of risk factors is essential to develop comprehensive intervention strategies preventing pregnancy-related complications. Our objective was to describe maternal mortality rates in a large, multi-country dataset and to determine maternal, pregnancy-related, delivery and postpartum characteristics that are associated with maternal mortality. Methods: We collected data describing all pregnancies from 2010 to 2013 among women enrolled in the multinational Global Network for Women's and Children's Health Research Maternal and Neonatal Health Registry (MNHR). We reported the proportion of mothers who died per pregnancy and the maternal mortality ratio (MMR). Generalized linear models were used to evaluate the relationship of potential medical and social factors and maternal mortality and to develop point and interval estimates of relative risk associated with these factors. Generalized estimating equations were used to account for the correlation of outcomes within cluster to develop appropriate confidence intervals. Results: We recorded 277,736 pregnancies and 402 maternal deaths for an MMR of 153/100,000 live births. We observed an improvement in the total MMR from 166 in 2010 to 126 in 2013. The MMR in Latin American sites (91) was lower than the MMR in Asian (178) and African sites (125). When adjusted for study site and the other variables, no formal education (RR 3.2 [1.5, 6.9]), primary education only (RR 3.4 [1.6, 7.5]), secondary education only (RR 2.5 [1.1, 5.7]), lack of antenatal care (RR 1.8 [1.2, 2.5]), caesarean section delivery (RR 1.9 [1.3, 2.8]), hemorrhage (RR 3.3 [2.2, 5.1]), and hypertensive disorders (RR 7.4 [5.2, 10.4]) were associated with higher risks of death. Conclusions: The MNHR identified preventable causes of maternal mortality in diverse settings in low-and middle-income countries. The MNHR can be used to monitor public health strategies and determine their association with reducing maternal mortality. C1 [Bauserman, Melissa; Bose, Carl L.] Univ N Carolina, Sch Med, Dept Pediat, Div Neonatal Perinatal Med, Chapel Hill, NC USA. [Lokangaka, Adrien; Tshefu, Antoinette] Kinshasa Sch Publ Hlth, Kinshasa, DEM REP CONGO. [Thorsten, Vanessa; Wallace, Dennis D.; McClure, Elizabeth M.] RTI Int, Durham, NC USA. [Goudar, Shivaprasad S.; Kodkany, Bhala] KLE Univ, Jawaharlal Nehru Med Coll, Belgaum, India. [Esamai, Fabian] Moi Univ, Sch Med, Eldoret, Kenya. [Garces, Ana] Fdn Alimentac & Nutr, Ctr Amer & Panama, Guatemala City, Guatemala. [Saleem, Sarah; Pasha, Omrana] Aga Khan Univ, Karachi, Pakistan. [Patel, Archana] Lata Med Res Fdn, Nagpur, Maharashtra, India. [Manasyan, Albert; Chomba, Elwyn] Univ Teaching Hosp, Lusaka, Zambia. [Berrueta, Mabel; Althabe, Fernando] Univ Buenos Aires, Inst Clin Effectiveness & Hlth Policy, RA-1053 Buenos Aires, DF, Argentina. [Liechty, Edward A.] Indiana Univ, Sch Med, Indianapolis, IN USA. [Hambidge, K. Michael; Krebs, Nancy F.] Univ Colorado, Sch Med, Boulder, CO 80309 USA. [Derman, Richard J.] Christiana Hlth Care, Newark, DE USA. [Hibberd, Patricia L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Carlo, Waldemar A.] Univ Alabama Birmingham, Birmingham, AL USA. [Koso-Thomas, Marion] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Goldenberg, Robert L.] Columbia Univ, Sch Med, Dept Obstet & Gynecol, New York, NY 10027 USA. RP Bauserman, M (reprint author), Univ N Carolina, Sch Med, Dept Pediat, Div Neonatal Perinatal Med, Chapel Hill, NC USA. EM Melissa_bauserman@med.unc.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development of the US National Institutes of Health [U01 HD040477, U01HD040636, U10HD078437, U10HD076461, U10HD076465, U10HD076457, U10HD078439, U10HD078438, U10HD076474] FX The project was funded by grants (U01 HD040477, U01HD040636, U10HD078437, U10HD076461, U10HD076465, U10HD076457, U10HD078439, U10HD078438, and U10HD076474) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the US National Institutes of Health. NR 19 TC 3 Z9 3 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4755 J9 REPROD HEALTH JI Reprod. Health PY 2015 VL 12 SU 2 AR S5 DI 10.1186/1742-4755-12-S2-S5 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DG8LU UT WOS:000372336400005 PM 26062992 ER PT J AU Bucher, S Marete, I Tenge, C Liechty, EA Esamai, F Patel, A Goudar, SS Kodkany, B Garces, A Chomba, E Althabe, F Barreuta, M Pasha, O Hibberd, P Derman, RJ Otieno, K Hambidge, KM Krebs, NF Carlo, WA Chemweno, C Goldenberg, RL McClure, EM Moore, JL Wallace, DD Saleem, S Koso-Thomas, M AF Bucher, Sherri Marete, Irene Tenge, Constance Liechty, Edward A. Esamai, Fabian Patel, Archana Goudar, Shivaprasad S. Kodkany, Bhalchandra Garces, Ana Chomba, Elwyn Althabe, Fernando Barreuta, Mabel Pasha, Omrana Hibberd, Patricia Derman, Richard J. Otieno, Kevin Hambidge, K. Michael Krebs, Nancy F. Carlo, Waldemar A. Chemweno, Carolyne Goldenberg, Robert L. McClure, Elizabeth M. Moore, Janet L. Wallace, Dennis D. Saleem, Sarah Koso-Thomas, Marion TI A prospective observational description of frequency and timing of antenatal care attendance and coverage of selected interventions from sites in Argentina, Guatemala, India, Kenya, Pakistan and Zambia SO REPRODUCTIVE HEALTH LA English DT Article ID MIDDLE-INCOME COUNTRIES; PREGNANT-WOMEN; WESTERN KENYA; BIRTH PREPAREDNESS; MATERNAL HEALTH; RISK-FACTORS; STILLBIRTHS; DELIVERY; MALARIA; ANEMIA AB Background: The Global Network for Women's and Children's Health Research is one of the largest international networks for testing and generating evidence-based recommendations for improvement of maternal-child health in resource-limited settings. Since 2009, Global Network sites in six low and middle-income countries have collected information on antenatal care practices, which are important as indicators of care and have implications for programs to improve maternal and child health. We sought to: (1) describe the quantity of antenatal care attendance over a four-year period; and (2) explore the quality of coverage for selected preventative, screening, and birth preparedness components. Methods: The Maternal Newborn Health Registry (MNHR) is a prospective, population-based birth and pregnancy outcomes registry in Global Network sites, including: Argentina, Guatemala, India (Belgaum and Nagpur), Kenya, Pakistan, and Zambia. MNHR data from these sites were prospectively collected from January 1, 2010 -December 31, 2013 and analyzed for indicators related to quantity and patterns of ANC and coverage of key elements of recommended focused antenatal care. Descriptive statistics were generated overall by global region (Africa, Asia, and Latin America), and for each individual site. Results: Overall, 96% of women reported at least one antenatal care visit. Indian sites demonstrated the highest percentage of women who initiated antenatal care during the first trimester. Women from the Latin American and Indian sites reported the highest number of at least 4 visits. Overall, 88% of women received tetanus toxoid. Only about half of all women reported having been screened for syphilis (49%) or anemia (50%). Rates of HIV testing were above 95% in the Argentina, African, and Indian sites. The Pakistan site demonstrated relatively high rates for birth preparation, but for most other preventative and screening interventions, posted lower coverage rates as compared to other Global Network sites. Conclusions: Results from our large, prospective, population-based observational study contribute important insight into regional and site-specific patterns for antenatal care access and coverage. Our findings indicate a quality and coverage gap in antenatal care services, particularly in regards to syphilis and hemoglobin screening. We have identified site-specific gaps in access to, and delivery of, antenatal care services that can be targeted for improvement in future research and implementation efforts. C1 [Bucher, Sherri; Liechty, Edward A.; Chemweno, Carolyne] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN 46202 USA. [Marete, Irene; Tenge, Constance; Esamai, Fabian; Otieno, Kevin] Moi Univ, Sch Med, Child Hlth & Paediat, Eldoret, Kenya. [Patel, Archana] Indira Gandhi Govt Med Coll, Nagpur, Maharashtra, India. [Patel, Archana] Lata Med Res Fdn, Nagpur, Maharashtra, India. [Goudar, Shivaprasad S.; Kodkany, Bhalchandra] KLE Univ Jawaharlal Nehru Med Coll, Belgaum, India. [Garces, Ana] Fdn Alimentac & Nutr Ctr Amer & Panama, Guatemala City, Guatemala. [Chomba, Elwyn] Univ Teaching Hosp, Lusaka, Zambia. [Althabe, Fernando; Barreuta, Mabel] Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina. [Pasha, Omrana; Saleem, Sarah] Aga Khan Univ, Karachi, Pakistan. [Hibberd, Patricia] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Derman, Richard J.] Christiana Care Hlth Syst, Newark, DE USA. [Hambidge, K. Michael; Krebs, Nancy F.] Univ Denver, Sch Med, Denver, CO USA. [Carlo, Waldemar A.] Univ Alabama Birmingham, Birmingham, AL USA. [Goldenberg, Robert L.] Columbia Univ, Dept Obstet Gynecol, New York, NY USA. [McClure, Elizabeth M.; Moore, Janet L.; Wallace, Dennis D.] RTI Int, Durham, NC USA. [Koso-Thomas, Marion] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Bucher, S (reprint author), Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN 46202 USA. EM shbucher@iu.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development of the US National Institutes of Health [U01 HD040477, U01HD040636, U10HD078437, U10HD076461, U10HD076465, U10HD076457, U10HD078439, U10HD078438, U10HD076474] FX The project was funded by grants (U01 HD040477, U01HD040636, U10HD078437, U10HD076461, U10HD076465, U10HD076457, U10HD078439, U10HD078438, and U10HD076474) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the US National Institutes of Health. NR 68 TC 3 Z9 3 U1 2 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4755 J9 REPROD HEALTH JI Reprod. Health PY 2015 VL 12 SU 2 AR S12 DI 10.1186/1742-4755-12-S2-S12 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DG8LU UT WOS:000372336400012 PM 26063483 ER PT J AU Goudar, SS Goco, N Somannavar, MS Vernekar, SS Mallapur, AA Moore, JL Wallace, DD Sloan, NL Patel, A Hibberd, PL Koso-Thomas, M McClure, EM Goldenberg, RL AF Goudar, Shivaprasad S. Goco, Norman Somannavar, Manjunath S. Vernekar, Sunil S. Mallapur, Ashalata A. Moore, Janet L. Wallace, Dennis D. Sloan, Nancy L. Patel, Archana Hibberd, Patricia L. Koso-Thomas, Marion McClure, Elizabeth M. Goldenberg, Robert L. TI Institutional deliveries and perinatal and neonatal mortality in Southern and Central India SO REPRODUCTIVE HEALTH LA English DT Article ID JANANI-SURAKSHA-YOJANA; LOW-RESOURCE SETTINGS; DEVELOPING-COUNTRIES; MATERNAL MORTALITY; GLOBAL-NETWORK; OBSTETRIC CARE; STILLBIRTH; INTRAPARTUM; KARNATAKA; IMPACT AB Background: Skilled birth attendance and institutional delivery have been advocated for reducing maternal, perinatal and neonatal mortality (PMR and NMR). India has successfully implemented various strategies to promote skilled attendance and incentivize institutional deliveries in the last 5 years. Objectives: The study evaluates the trends in institutional delivery, PMR, NMR, and their risk factors in two Eunice Kennedy Shriver NICHD Global Network for Women's and Children's Health Research sites, in Belgaum and Nagpur, India, between January 2010 and December 2013. Design/methods: Descriptive data stratified by level of delivery care and key risk factors were analyzed for 36 geographic clusters providing 48 months of data from a prospective, population-based surveillance system that registers all pregnant permanent residents in the study area, and their pregnancy outcomes irrespective of where they deliver. Log binomial models with generalized estimating equations to control for correlation of clustered observations were used to test the trends significance Results: 64,803 deliveries were recorded in Belgaum and 39,081 in Nagpur. Institutional deliveries increased from 92.6% to 96.1% in Belgaum and from 89.5% to 98.6% in Nagpur (both p< 0.0001); hospital rates increased from 63.4% to 71.0% (p= 0.002) and from 63.1% to 72.0% (p< 0.0001), respectively. PMR declined from 41.3 to 34.6 (p= 0.008) deaths per 1,000 births in Belgaum and from 47.4 to 40.8 (p= 0.09) in Nagpur. Stillbirths also declined, from 22.5 to 16.3 per 1,000 births in Belgaum and from 29.3 to 21.1 in Nagpur (both p= 0.002). NMR remained unchanged. Conclusions: Significant increases in institutional deliveries, particularly in hospitals, were accompanied by reductions in stillbirths and PMR, but not by NMR. C1 [Goudar, Shivaprasad S.; Somannavar, Manjunath S.; Vernekar, Sunil S.] KLE Univ Jawaharlal Nehru Med Coll, Womens & Childrens Hlth Res Unit, Belgaum, Karnataka, India. [Goco, Norman; Moore, Janet L.; Wallace, Dennis D.; McClure, Elizabeth M.] RTI Int, Durham, NC USA. [Mallapur, Ashalata A.] S Nijalingappa Med Coll, Bagalkot, Karnataka, India. [Sloan, Nancy L.] Christiana Care Hlth Syst, Newark, DE USA. [Patel, Archana] Latta Med Res Fdn, Nagpur, Maharashtra, India. [Hibberd, Patricia L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Koso-Thomas, Marion] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Goldenberg, Robert L.] Columbia Univ, Sch Med, Dept Obstet & Gynecol, New York, NY USA. RP Goudar, SS (reprint author), KLE Univ Jawaharlal Nehru Med Coll, Womens & Childrens Hlth Res Unit, Belgaum, Karnataka, India. EM sgoudar@jnmc.edu OI Somannavar, Manjunath/0000-0002-8871-5072 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [U01 HD040477, U01 HD043475, U01 HD043464, U01 HD040657, U01 HD042372, U01 HD040607, U01HD040636, U01 HD040574, U01 HD40636] FX The study was funded by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (U01 HD040477, U01 HD043475, U01 HD043464, U01 HD040657, U01 HD042372, U01 HD040607, U01HD040636, U01 HD040574, U01 HD40636). NR 29 TC 3 Z9 3 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4755 J9 REPROD HEALTH JI Reprod. Health PY 2015 VL 12 SU 2 AR S13 DI 10.1186/1742-4755-12-S2-S13 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DG8LU UT WOS:000372336400013 PM 26063586 ER PT J AU Marete, I Tenge, C Chemweno, C Bucher, S Pasha, O Ramadurg, UY Mastiholi, SC Chiwila, M Patel, A Althabe, F Garces, A Moore, JL Liechty, EA Derman, RJ Hibberd, PL Hambidge, KM Goldenberg, RL Carlo, WA Koso-Thomas, M McClure, EM Esamai, F AF Marete, Irene Tenge, Constance Chemweno, Carolyne Bucher, Sherri Pasha, Omrana Ramadurg, Umesh Y. Mastiholi, Shivanand C. Chiwila, Melody Patel, Archana Althabe, Fernando Garces, Ana Moore, Janet L. Liechty, Edward A. Derman, Richard J. Hibberd, Patricia L. Hambidge, K. Michael Goldenberg, Robert L. Carlo, Waldemar A. Koso-Thomas, Marion McClure, Elizabeth M. Esamai, Fabian TI Lost to follow-up among pregnant women in a multi-site community based maternal and newborn health registry: a prospective study SO REPRODUCTIVE HEALTH LA English DT Article ID CARE; SERVICES; KENYA; HIV AB Background: It is important when conducting epidemiologic studies to closely monitor lost to follow up (LTFU) rates. A high LTFU rate may lead to incomplete study results which in turn can introduce bias to the trial or study, threatening the validity of the findings. There is scarce information on LTFU in prospective community-based perinatal epidemiological studies. This paper reports the rates of LTFU, describes socio-demographic characteristics, and pregnancy/delivery outcomes of mothers LTFU in a large community-based pregnancy registry study. Methods: Data were from a prospective, population-based observational study of the Global Network for Women's and Children's Health Research Maternal Newborn Health Registry (MNHR). This is a multi-centre, international study in which pregnant women were enrolled in mid-pregnancy, followed through parturition and 42 days post-delivery. Risk for LTFU was calculated within a 95% CI. Results: A total of 282,626 subjects were enrolled in this study, of which 4,893 were lost to follow-up. Overall, there was a 1.7% LTFU to follow up rate. Factors associated with a higher LTFU included mothers who did not know their last menstrual period (RR 2.2, 95% CI 1.1, 4.4), maternal age of < 20 years (RR 1.2, 95% CI 1.1, 1.3), women with no formal education (RR 1.2, 95% CI 1.1, 1.4), and attending a government clinic for antenatal care (RR 2.0, 95% CI 1.4, 2.8). Post-natal factors associated with a higher LTFU rate included a newborn with feeding problems (RR 1.6, 94% CI 1.2, 2.2). Conclusions: The LTFU rate in this community-based registry was low (1.7%). Maternal age, maternal level of education, pregnancy status at enrollment and using a government facility for ANC are factors associated with being LTFU. Strategies to ensure representation and high retention in community studies are important to informing progress toward public health goals. C1 [Marete, Irene; Tenge, Constance; Chemweno, Carolyne; Esamai, Fabian] Moi Univ, Dept Child Hlth & Paediat, Sch Med, Eldoret, Kenya. [Bucher, Sherri; Liechty, Edward A.] Indiana Univ, Riley Hosp, Dept Paediat, Indianapolis, IN 46204 USA. [Pasha, Omrana] Aga Khan Univ, Dept Community Hlth Serv, Karachi, Pakistan. [Ramadurg, Umesh Y.] S Nijalingappa Med Coll, Bagalkot, Karnataka, India. [Mastiholi, Shivanand C.] KLE Univ, Jawaharlal Nehru Med Coll, Belgaum, Karnataka, India. [Chiwila, Melody] Univ Teaching Hosp, Lusaka, Zambia. [Patel, Archana] Lata Med Res Fdn, Nagpur, Maharashtra, India. [Althabe, Fernando] Inst Clin Effectiveness, Buenos Aires, DF, Argentina. [Garces, Ana] Francisco Marroquin Univ, Multidisciplinary Hlth Inst, Guatemala City, Guatemala. [Moore, Janet L.; McClure, Elizabeth M.] RTI Int, Durham, NC USA. [Derman, Richard J.] Christiana Care Hlth Syst, Wilmington, DC USA. [Hibberd, Patricia L.] Massachusetts Gen Hosp, Div Global Hlth, Boston, MA 02114 USA. [Hambidge, K. Michael] Univ Colorado, Dept Paediat, Denver, CO 80202 USA. [Goldenberg, Robert L.] Columbia Univ, New York, NY USA. [Carlo, Waldemar A.] Univ Alabama Birmingham, Dept Paediat, Birmingham, AL USA. [Koso-Thomas, Marion] NICHHD, Bethesda, MD 20892 USA. RP Marete, I (reprint author), Moi Univ, Dept Child Hlth & Paediat, Sch Med, Eldoret, Kenya. EM mareteirene07@yahoo.com FU Eunice Kennedy Shriver National Institute of Child Health and Human Development of the US National Institutes of Health United State of America [U01 HD040477, U01HD040636, U10HD078437, U10HD076461, U10HD076465, U10HD076457, U10HD078439, U10HD078438, U10HD076474] FX We acknowledge the work of all the Registry Administrators in the seven Global Network sites. This work was supported by grants (U01 HD040477, U01HD040636, U10HD078437, U10HD076461, U10HD076465, U10HD076457, U10HD078439, U10HD078438, and U10HD076474) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the US National Institutes of Health United State of America. NR 17 TC 1 Z9 1 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4755 J9 REPROD HEALTH JI Reprod. Health PY 2015 VL 12 SU 2 AR S4 DI 10.1186/1742-4755-12-S2-S4 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DG8LU UT WOS:000372336400004 PM 26062899 ER PT J AU McClure, EM Saleem, S Goudar, SS Moore, JL Garces, A Esamai, F Patel, A Chomba, E Althabe, F Pasha, O Kodkany, BS Bose, CL Berreuta, M Liechty, EA Hambidge, KM Krebs, NF Derman, RJ Hibberd, PL Buekens, P Manasyan, A Carlo, WA Wallace, DD Koso-Thomas, M Goldenberg, RL AF McClure, Elizabeth M. Saleem, Sarah Goudar, Shivaprasad S. Moore, Janet L. Garces, Ana Esamai, Fabian Patel, Archana Chomba, Elwyn Althabe, Fernando Pasha, Omrana Kodkany, Bhalachandra S. Bose, Carl L. Berreuta, Mabel Liechty, Edward A. Hambidge, K. Michael Krebs, Nancy F. Derman, Richard J. Hibberd, Patricia L. Buekens, Pierre Manasyan, Albert Carlo, Waldemar A. Wallace, Dennis D. Koso-Thomas, Marion Goldenberg, Robert L. TI Stillbirth rates in low-middle income countries 2010-2013: a population-based, multi-country study from the Global Network SO REPRODUCTIVE HEALTH LA English DT Article ID LOW-RESOURCE SETTINGS; PERINATAL-MORTALITY; CESAREAN DELIVERY; OBSTETRIC CARE; PREGNANCY OUTCOMES; NEONATAL DEATHS; NEWBORN HEALTH; INTRAPARTUM; DETERMINANTS; BANGLADESH AB Background: Stillbirth rates remain nearly ten times higher in low-middle income countries (LMIC) than high income countries. In LMIC, where nearly 98% of stillbirths worldwide occur, few population-based studies have documented characteristics or care for mothers with stillbirths. Non-macerated stillbirths, those occurring around delivery, are generally considered preventable with appropriate obstetric care. Methods: We undertook a prospective, population-based observational study of all pregnant women in defined geographic areas across 7 sites in low-resource settings (Kenya, Zambia, India, Pakistan, Guatemala and Argentina). Staff collected demographic and health care characteristics with outcomes obtained at delivery. Results: From 2010 through 2013, 269,614 enrolled women had 272,089 births, including 7,865 stillbirths. The overall stillbirth rate was 28.9/1000 births, ranging from 13.6/1000 births in Argentina to 56.5/1000 births in Pakistan. Stillbirth rates were stable or declined in 6 of the 7 sites from 2010-2013, only increasing in Pakistan. Less educated, older and women with less access to antenatal care were at increased risk of stillbirth. Furthermore, women not delivered by a skilled attendant were more likely to have a stillbirth (RR 2.8, 95% CI 2.2, 3.5). Compared to live births, stillbirths were more likely to be preterm (RR 12.4, 95% CI 11.2, 13.6). Infants with major congenital anomalies were at increased risk of stillbirth (RR 9.1, 95% CI 7.3, 11.4), as were multiple gestations (RR 2.8, 95% CI 2.4, 3.2) and breech (RR 3.0, 95% CI 2.6, 3.5). Altogether, 67.4% of the stillbirths were non-macerated. 7.6% of women with stillbirths had cesarean sections, with obstructed labor the primary indication (36.9%). Conclusions: Stillbirth rates were high, but with reductions in most sites during the study period. Disadvantaged women, those with less antenatal care and those delivered without a skilled birth attendant were at increased risk of delivering a stillbirth. More than two-thirds of all stillbirths were non-macerated, suggesting potentially preventable stillbirth. Additionally, 8% of women with stillbirths were delivered by cesarean section. The relatively high rate of cesarean section among those with stillbirths suggested that this care was too late or not of quality to prevent the stillbirth; however, further research is needed to evaluate the quality of obstetric care, including cesarean section, on stillbirth in these low resource settings. C1 [McClure, Elizabeth M.; Moore, Janet L.] RTI Int, Durham, NC USA. [Saleem, Sarah; Pasha, Omrana] Aga Khan Univ, Karachi, Pakistan. [Goudar, Shivaprasad S.; Kodkany, Bhalachandra S.] KLE Univ, Jawaharlal Nehru Med Coll, Belgaum, India. [Garces, Ana] Fdn Alimentac Nutr, Ctr Amer & Panama, Guatemala City, Guatemala. [Esamai, Fabian] Moi Univ, Sch Med, Eldoret, Kenya. [Patel, Archana] Lata Med Res Fdn, Nagpur, Maharashtra, India. [Chomba, Elwyn] Univ Teaching Hosp, Lusaka, Zambia. [Althabe, Fernando; Berreuta, Mabel] Univ Buenos Aires, Inst Clin Effectiveness & Hlth Policy, RA-1053 Buenos Aires, DF, Argentina. [Bose, Carl L.] Univ N Carolina, Chapel Hill, NC USA. [Liechty, Edward A.] Indiana Univ, Sch Med, Indianapolis, IN USA. [Hambidge, K. Michael; Krebs, Nancy F.] Univ Denver, Sch Med, Denver, CO USA. [Derman, Richard J.] Christiana Care Hlth Syst, Newark, DE USA. [Hibberd, Patricia L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Buekens, Pierre] Tulane Sch Publ Hlth & Trop Med, New Orleans, LA USA. [Manasyan, Albert; Carlo, Waldemar A.] Univ Alabama Birmingham, Birmingham, AL USA. [Koso-Thomas, Marion] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Goldenberg, Robert L.] Columbia Univ, Sch Med, Dept Obstet & Gynecol, New York, NY USA. RP McClure, EM (reprint author), RTI Int, Durham, NC USA. EM mcclure@rti.org FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [U01 HD040477, U01HD040636, U10HD078437, U10HD076461, U10HD076465, U10HD076457, U10HD078439, U10HD078438, U10HD076474] FX The study was funded by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (U01 HD040477, U01HD040636, U10HD078437, U10HD076461, U10HD076465, U10HD076457, U10HD078439, U10HD078438, and U10HD076474). NR 31 TC 11 Z9 11 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4755 J9 REPROD HEALTH JI Reprod. Health PY 2015 VL 12 SU 2 AR S7 DI 10.1186/1742-4755-12-S2-S7 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DG8LU UT WOS:000372336400007 PM 26063292 ER PT S AU Ilic, MM Perovic, I Tonyushkin, AA Athalye, P Sekeljic, N Notaros, BM AF Ilic, M. M. Perovic, I. Tonyushkin, A. A. Athalye, P. Sekeljic, N. Notaros, B. M. GP IEEE TI Full-Wave Frequency-Domain Electromagnetic Modelling of RF Fields in MRI Applications SO 2015 IEEE INTERNATIONAL SYMPOSIUM ON ANTENNAS AND PROPAGATION & USNC/URSI NATIONAL RADIO SCIENCE MEETING SE IEEE Antennas and Propagation Society International Symposium LA English DT Proceedings Paper CT IEEE International Symposium on Antennas and Propagation / USNC/URSI National North American Radio Science Meeting CY JUL 19-24, 2015 CL Vancouver, CANADA SP Inst Elect & Elect Engineers, IEEE Antennas & Propagat Soc, USNC, URSI AB We show that full-wave frequency-domain electromagnetic (EM) methods can be efficiently used in RF designs for magnetic resonance imaging (MRI) applications. We also compare the results obtained by the higher order surface integral equation (SIE)-based method of moments (MoM) and the finite element method (FEM), namely, HFSS, which are in excellent agreement. Finally, we present important details of MoM-SIE and FEM (HFSS) modeling, which enable rigorous analyses and cross-validation of the solutions. C1 [Ilic, M. M.; Perovic, I.] Univ Belgrade, Sch Elect Engn, Belgrade, Serbia. [Tonyushkin, A. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Athalye, P.; Sekeljic, N.; Notaros, B. M.] Colorado State Univ, Elect & Comp Engn Dept, Ft Collins, CO 80523 USA. RP Ilic, MM (reprint author), Univ Belgrade, Sch Elect Engn, Belgrade, Serbia. EM milanilic@etf.rs; ivana.ivy.perovic@gmail.com; atonyushkin@mgh.harvard.edu; athalye@rams.colostate.edu; inadasek@engr.colostate.edu; notaros@colostate.edu NR 3 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1522-3965 BN 978-1-4799-7815-1 J9 IEEE ANTENNAS PROP PY 2015 BP 971 EP 972 PG 2 WC Telecommunications SC Telecommunications GA BE3YW UT WOS:000371401401043 ER PT S AU Ilic, MM Tonyushkin, AA Sekeljic, N Athalye, P Notaros, BM AF Ilic, M. M. Tonyushkin, A. A. Sekeljic, N. Athalye, P. Notaros, B. M. GP IEEE TI RF Excitation in 7 Tesla MRI Systems Using Monofilar Axial-Mode Helical Antenna SO 2015 IEEE INTERNATIONAL SYMPOSIUM ON ANTENNAS AND PROPAGATION & USNC/URSI NATIONAL RADIO SCIENCE MEETING SE IEEE Antennas and Propagation Society International Symposium LA English DT Proceedings Paper CT IEEE International Symposium on Antennas and Propagation / USNC/URSI National North American Radio Science Meeting CY JUL 19-24, 2015 CL Vancouver, CANADA SP Inst Elect & Elect Engineers, IEEE Antennas & Propagat Soc, USNC, URSI AB We present a novel RF exciter for traveling-wave magnetic resonance imaging (MRI) systems based on a monofilar axial-mode helical antenna. In specific, we present a bore-extended, subject-loaded monofilar helical antenna for 7-T (ultra-high magnetic field) MRI systems. By means of rigorous full-wave electromagnetic modeling, we confirm clear advantages of the novel exciter over the existing TW excitation methods, and its excellent performance in terms of circular polarization and uniformity of the RF magnetic field in simple phantoms inside MRI bores at 7 T. C1 [Ilic, M. M.] Univ Belgrade, Sch Elect Engn, Belgrade, Serbia. [Tonyushkin, A. A.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Sekeljic, N.; Athalye, P.; Notaros, B. M.] Colorado State Univ, Dept Elect & Comp Engn, Ft Collins, CO 80523 USA. RP Ilic, MM (reprint author), Univ Belgrade, Sch Elect Engn, Belgrade, Serbia. EM notaros@colostate.edu NR 5 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1522-3965 BN 978-1-4799-7815-1 J9 IEEE ANTENNAS PROP PY 2015 BP 1346 EP 1347 PG 2 WC Telecommunications SC Telecommunications GA BE3YW UT WOS:000371401401226 ER PT J AU Song, Q Ma, YL Song, JQ Chen, Q Xia, GS Ma, JY Feng, F Fei, XJ Wang, QM AF Song, Q. Ma, Y. L. Song, J. Q. Chen, Q. Xia, G. S. Ma, J. Y. Feng, F. Fei, X. J. Wang, Q. M. TI Sevoflurane induces neurotoxicity in young mice through FAS/FASL signaling SO GENETICS AND MOLECULAR RESEARCH LA English DT Article DE Sevoflurane; Apoptosis; Neurogenesis; Fas/FasL ID EARLY EXPOSURE; IMMUNE-SYSTEM; ANESTHESIA; NEUROGENESIS; PATHWAY; BRAIN; CELLS; FETAL AB Sevoflurane, the most widely used anesthetic in clinical practice, has been shown to induce apoptosis, inhibit neurogenesis, and cause learning and memory impairment in young mice. However, the underlying mechanism is still unknown. In this study, wild-type and the FAS- or FAS ligand (FASL)-knockout mice (age 7 days) were exposed to sevoflurane or pure oxygen. Western blotting was used to examine the expression of FAS protein. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and bromodeoxyuridine (BrdU) staining were employed to quantify the apoptotic cells and newborn cells in the hippocampus and Morris water maze (MWM) in order to evaluate learning and memory status. Sevoflurane significantly increased the expression of FAS protein in wild-type mice. Compared to FAS- and FASL-knockout mice treated with sevoflurane, sevoflurane-treated wildtype mice exhibited more TUNEL-positive hippocampal cells and less BrdU-positive hippocampal cells. The MWM showed that compared with FAS- and FASL-knockout mice treated with sevoflurane, sevoflurane treatment of wildtype mice significantly prolonged the escape latency and reduced platform crossing times. These data suggest that sevoflurane induces neurotoxicity in young mice through FAS- FASL signaling. C1 [Song, Q.; Ma, Y. L.; Song, J. Q.; Chen, Q.; Xia, G. S.; Ma, J. Y.; Feng, F.; Wang, Q. M.] Zhengzhou Cent Hosp, Dept Anesthesiol, Zhengzhou, Henan Province, Peoples R China. [Fei, X. J.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Charlestown, MA USA. [Fei, X. J.] Harvard Univ, Sch Med, Charlestown, MA USA. [Fei, X. J.] Shanghai Univ Tradit Chinese Med, Shuguang Hosp, Dept Hosp Infect, Shanghai, Peoples R China. RP Fei, XJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Charlestown, MA USA. EM weiymzhl@aliyun.com; min2178@163.com FU Technical Cooperation of the International Division of Zhengzhou [20140966] FX Research supported by the Technical Cooperation of the International Division of Zhengzhou (#20140966). NR 16 TC 2 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 2015 VL 14 IS 4 BP 18059 EP 18068 DI 10.4238/2015.December.22.32 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA DF8DN UT WOS:000371587400081 PM 26782453 ER PT S AU Hui, PC Rodriguez, A Woolf, D Iwase, E Khan, M Capasso, F Loncar, M AF Hui, Pui-Chuen Rodriguez, Alejandro Woolf, David Iwase, Eiji Khan, Mughees Capasso, Federico Loncar, Marko GP IEEE TI Strong Mechanical Nonlinearity of Optomechanically Driven Suspended Photonic Crystal Membrane SO 2015 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) SE Conference on Lasers and Electro-Optics LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO) CY MAY 10-15, 2015 CL San Jose, CA AB We demonstrated the nonlinear mechanics of an optomechnaically driven silicon membrane suspended 100nm over a nearby substrate. The estimated optical force-induced Duffing nonlinearity is 10(28)Hz(2)/m(2), significantly larger than that afforded by the nonlinear Casimir potential. C1 [Hui, Pui-Chuen; Capasso, Federico; Loncar, Marko] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Hui, Pui-Chuen] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Rodriguez, Alejandro] Princeton Univ, Dept Elect Engn, Princeton, NJ 08544 USA. [Woolf, David] Phys Sci Inc, Andover, MA 01810 USA. [Iwase, Eiji] Waseda Univ, Dept Appl Mech & Aerosp Engn, Tokyo 1698555, Japan. [Khan, Mughees] Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA. RP Hui, PC (reprint author), Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. EM phui1@mgh.harvard.edu RI Iwase, Eiji/B-2234-2012 NR 4 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2160-9020 BN 978-1-55752-968-8 J9 CONF LASER ELECTR PY 2015 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BE3EW UT WOS:000370627102234 ER PT S AU Humar, M Yun, SH AF Humar, Matjaz Yun, Seok-Hyun GP IEEE TI Microlasers Inside Live Cells SO 2015 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) SE Conference on Lasers and Electro-Optics LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO) CY MAY 10-15, 2015 CL San Jose, CA ID OPTICAL MICROCAVITIES; LABEL-FREE; SINGLE AB Here we show, for the first time to our knowledge, stand-alone cell lasers with both gain medium and cavity inside cells. Cells have natural tendency to engulf micro beads made of polystyrene or glass, and we use these microspheres to generate whispering-galley-mode (WGM) lasing inside cytoplasm. The gain was provided by fluorescent dye molecules embedded in the microspheres or in the cytosol. Upon optical pumping, the output emission from the cells show characteristic WGM resonance. By analyzing the wavelengths of the oscillation modes we can determine the bead size with a precision of 50 pm. Using the mode diameter as a unique identifier, one may distinguish more than thousands of cells. Furthermore, we demonstrate real-time sensing of the intracellular refractive index changes. C1 [Humar, Matjaz; Yun, Seok-Hyun] Harvard Univ, Sch Med, Dept Dermatol, Wellman Ctr Photomed, 65 Landsdowne St UP-5, Cambridge, MA 02139 USA. [Humar, Matjaz; Yun, Seok-Hyun] Massachusetts Gen Hosp, Cambridge, MA 02139 USA. [Humar, Matjaz] Jozef Stefan Inst, Condensed Matter Dept, Ljubljana 1000, Bangladesh. RP Humar, M (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Wellman Ctr Photomed, 65 Landsdowne St UP-5, Cambridge, MA 02139 USA. EM mhumar@mgh.harvard.edu RI Humar, Matjaz/I-8862-2012 OI Humar, Matjaz/0000-0003-3338-6723 NR 12 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2160-9020 BN 978-1-55752-968-8 J9 CONF LASER ELECTR PY 2015 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BE3EW UT WOS:000370627103069 ER PT S AU Humar, M Yun, SH AF Humar, Matjaz Yun, Seok-Hyun GP IEEE TI Analysis of Optical Properties of Cell Lasers and Their Use as Biological Sensors SO 2015 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) SE Conference on Lasers and Electro-Optics LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO) CY MAY 10-15, 2015 CL San Jose, CA ID GREEN FLUORESCENT PROTEIN AB We analyzed single-cell lasers made from different cell types and a variety of organic fluorescent dyes commonly employed for staining cells. Adherent cells or cell suspension is placed in between two highly reflective dielectric mirrors, which form a laser cavity. The rounded shape of the cell acts as a lens making a stable laser cavity. The resonator stability is dependent on the resonator gap, cell size and refractive index. We investigated the effects of gain dye distribution inside and outside the cells. The cell laser thresholds were calculated to optimize the dye concentration, resonator gap and selection of the dye. The different transversal cell laser modes are dependent on cell shape and refractive index distribution. By measuring the laser modes we demonstrate single cell shape characterization and sensing. C1 [Humar, Matjaz; Yun, Seok-Hyun] Harvard Univ, Sch Med, Dept Dermatol, Wellman Ctr Photomed, 65 Landsdowne St UP 5, Cambridge, MA 02139 USA. [Humar, Matjaz; Yun, Seok-Hyun] Massachusetts Gen Hosp, Cambridge, MA 02139 USA. [Humar, Matjaz] Jozef Stefan Inst, Condensed Matter Dept, Ljubljana 1000, Slovenia. RP Humar, M (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Wellman Ctr Photomed, 65 Landsdowne St UP 5, Cambridge, MA 02139 USA. EM mhumar@mgh.harvard.edu RI Humar, Matjaz/I-8862-2012 OI Humar, Matjaz/0000-0003-3338-6723 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 2160-9020 BN 978-1-55752-968-8 J9 CONF LASER ELECTR PY 2015 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BE3EW UT WOS:000370627100023 ER PT S AU Ibrahim, A Ferachou, D Sharma, G Singh, K Ozaki, T AF Ibrahim, A. Ferachou, D. Sharma, G. Singh, K. Ozaki, T. GP IEEE TI Ultra High Dynamic Range Electro Optic Sampling for Terahertz Detection Using Fiber Based Spectral Domain Interferometry SO 2015 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) SE Conference on Lasers and Electro-Optics LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO) CY MAY 10-15, 2015 CL San Jose, CA AB We demonstrate a novel fiber-based spectral-domain interferometry (SDI) technique for terahertz electric field measurement. Signal-to-noise ratio is enhanced by more than four folds while the scanning window is extended to >30 picoseconds compared to conventional SDI techniques. C1 [Ibrahim, A.; Ferachou, D.; Ozaki, T.] Univ Quebec, Adv Laser Light Source, INRS EMT, 1650 Boul Lionel Boulet, Varennes, PQ J3X 1S2, Canada. [Sharma, G.] Univ Massachusetts, Lowell, MA 01854 USA. [Singh, K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ibrahim, A (reprint author), Univ Quebec, Adv Laser Light Source, INRS EMT, 1650 Boul Lionel Boulet, Varennes, PQ J3X 1S2, Canada. EM ibrahima@emt.inrs.ca NR 4 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2160-9020 BN 978-1-55752-968-8 J9 CONF LASER ELECTR PY 2015 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BE3EW UT WOS:000370627101283 ER PT S AU Maguluri, G Chang, E Iftimia, N Mehta, D Kobler, J AF Maguluri, Gopi Chang, Ernest Iftimia, Nicusor Mehta, Daryush Kobler, James GP IEEE TI Dynamic vocal fold imaging by integrating optical coherence tomography with laryngeal high-speed video endoscopy SO 2015 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) SE Conference on Lasers and Electro-Optics LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO) CY MAY 10-15, 2015 CL San Jose, CA AB We demonstrate three-dimensional vocal fold imaging during phonation by integrating optical coherence tomography with high-speed videoendoscopy. Results from ex vivo larynx experiments yield reconstructed vocal fold surface contours for ten phases of periodic motion. C1 [Maguluri, Gopi; Chang, Ernest; Iftimia, Nicusor] Phys Sci Inc, 20 New England Business Ctr, Andover, MA 01810 USA. [Mehta, Daryush; Kobler, James] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. RP Maguluri, G (reprint author), Phys Sci Inc, 20 New England Business Ctr, Andover, MA 01810 USA. 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 SN 2160-9020 BN 978-1-55752-968-8 J9 CONF LASER ELECTR PY 2015 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BE3EW UT WOS:000370627100072 ER PT S AU Nadkarni, SK Tripathi, M Tshikudi, D van Cott, E Hajjarian, Z AF Nadkarni, Seemantini K. Tripathi, Markandey Tshikudi, Diane van Cott, Elizabeth Hajjarian, Zeinab GP IEEE TI Blood Coagulation Sensing at the Point of Care SO 2015 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) SE Conference on Lasers and Electro-Optics LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO) CY MAY 10-15, 2015 CL San Jose, CA ID PREDICT TRANSFUSION; 1 HOUR; ADMISSION AB We describe a new optical coagulation sensing approach termed Optical Thromboelastography (OTEG) that measures a patient's coagulation status using a drop of blood. In OTEG, laser speckle intensity fluctuations are analyzed during clotting to measure the viscoelastic properties of blood during coagulation and recover information about multiple coagulation metrics within minutes. This technology addresses the critical unmet need to identify and manage patients with an elevated risk of life-threatening hemorrhage, the major cause of in-hospital preventable death. In addition, this innovation may enable rapid coagulation testing for patients who routinely receive oral anticoagulants to prevent venous and arterial thrombosis, the world's number one killer. C1 [Nadkarni, Seemantini K.; Tripathi, Markandey; Tshikudi, Diane; van Cott, Elizabeth; Hajjarian, Zeinab] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR 720,40 Blossom St, Boston, MA 02114 USA. RP Nadkarni, SK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR 720,40 Blossom St, Boston, MA 02114 USA. EM snadkarni@mgh.harvard.edu NR 8 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2160-9020 BN 978-1-55752-968-8 J9 CONF LASER ELECTR PY 2015 PG 3 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BE3EW UT WOS:000370627100075 ER PT S AU Villiger, M Lippok, N Bouma, BE AF Villiger, Martin Lippok, Norman Bouma, Brett E. GP IEEE TI Differential Mueller-matrix formalism for polarization sensitive optical coherence tomography SO 2015 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) SE Conference on Lasers and Electro-Optics LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO) CY MAY 10-15, 2015 CL San Jose, CA AB The differential Mueller matrix offers useful insight into the polarization properties of biological tissue imaged with polarization sensitive optical coherence tomography. We present the theory and experimentally demonstrate local depolarization in addition to local retardation. C1 [Villiger, Martin] Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Villiger, M (reprint author), Harvard Univ, Sch Med, 55 Fruit St, Boston, MA 02114 USA. EM mvilliger@mgh.harvard.edu NR 7 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2160-9020 BN 978-1-55752-968-8 J9 CONF LASER ELECTR PY 2015 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BE3EW UT WOS:000370627100119 ER PT S AU Yun, SHA AF Yun, Seok-Hyun Andy GP IEEE TI The Cell Laser SO 2015 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) SE Conference on Lasers and Electro-Optics LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO) CY MAY 10-15, 2015 CL San Jose, CA C1 [Yun, Seok-Hyun Andy] Harvard Univ, Sch Med, 65 Landsdowne St UP 525, Cambridge, MA 02139 USA. [Yun, Seok-Hyun Andy] Massachusetts Gen Hosp, Wellman Ctr Photomed, Cambridge, MA 02139 USA. RP Yun, SHA (reprint author), Harvard Univ, Sch Med, 65 Landsdowne St UP 525, Cambridge, MA 02139 USA. EM syun@hms.harvard.edu NR 2 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2160-9020 BN 978-1-55752-968-8 J9 CONF LASER ELECTR PY 2015 PG 1 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BE3EW UT WOS:000370627100022 ER PT B AU Robkin, M Weininger, S Preciado, B Goldman, J AF Robkin, Michael Weininger, Sandy Preciado, Benjamin Goldman, Julian GP IEEE TI Levels of Conceptual Interoperability Model for Healthcare Framework for Safe Medical Device Interoperability SO 2015 IEEE SYMPOSIUM ON PRODUCT COMPLIANCE ENGINEERING (ISPCE 2015) LA English DT Proceedings Paper CT 12th IEEE Annual Symposium on Product Compliance Engineering (ISPCE) CY MAY 18-20, 2015 CL Chicago, IL SP IEEE, IEEE Prod Safety Engn Soc, UL, LiftMaster, Dell, Nemko, In Compliance DE Medical Device; Safety; Conceptual; Dynamic; Pragmatic; Semantic; Syntactic Interoperability; Standards; LCIM; Plug-and-Play; PNP; Healthcare Information Technology; HIT; MD PnP AB The Medical Device and Healthcare Information Technology (HIT) industries have not achieved safe PNP cross-manufacturer (heterogeneous) interoperability although it has been achieved decades ago in other safety critical industries. We believe that the Levels of Conceptual Interoperability Model (LCIM) [1] offers an essential account of the disparity and thereby offers insight for how to achieve safe PNP cross-manufacturer interoperability in HIT. The LCIM is a conceptual framework for interoperability first developed for military simulation and modeling. We have expanded its scope and detail while applying it to medical devices. Our results show that safe interoperability minimally requires system components that are aligned about a conceptual model (i.e. manufacturers are operating at level 6). Furthermore, such devices can be assured to be safely interoperable cross-manufacturer only if different manufacturers share the conceptual model embodied by the communicating devices. We identify some root causes preventing this realization. C1 [Robkin, Michael; Preciado, Benjamin] Anakena Solut Inc, Woodland Hills, CA USA. [Weininger, Sandy] US FDA, CDRH, Silver Spring, MD USA. [Goldman, Julian] Massachusetts Gen Hosp, MD PnP Program, Boston, MA 02114 USA. RP Robkin, M (reprint author), Anakena Solut Inc, Woodland Hills, CA USA. EM MikeRobkin@gmail.com; Sandy.Weininger@fda.hhs.gov; bpreciado@live.com; jgoldman@mdpnp.org 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 978-1-4799-5930-3; 978-1-4799-5929-7 PY 2015 PG 8 WC Engineering, Industrial; Engineering, Electrical & Electronic SC Engineering GA BE3ZD UT WOS:000371412000004 ER PT S AU Villiger, M Lorenser, D Quirk, BC Kirk, RW Lippok, N Bouma, BE McLaughlin, RA Sampson, DD AF Villiger, Martin Lorenser, Dirk Quirk, Bryden C. Kirk, Rodney W. Lippok, Norman Bouma, Brett E. McLaughlin, Robert A. Sampson, David D. GP IEEE TI Polarization sensitive OCT with needle probes SO 2015 PHOTONICS CONFERENCE (IPC) SE IEEE Photonics Conference LA English DT Proceedings Paper CT IEEE Photonics Conference CY OCT 04-08, 2015 CL Reston, VA SP IEEE ID OPTICAL COHERENCE TOMOGRAPHY AB We demonstrate polarization sensitive OCT using miniaturized needle probes. Employing the Mueller-formalism, we reconstruct tissue birefringence and retrieve the depolarization index of ex vivo tissue samples, providing contrast complementary to the structural intensity signal. C1 [Villiger, Martin; Lippok, Norman; Bouma, Brett E.] Harvard Univ, Sch Med, Boston, MA USA. [Villiger, Martin; Lippok, Norman; Bouma, Brett E.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Lorenser, Dirk; Quirk, Bryden C.; Kirk, Rodney W.; McLaughlin, Robert A.; Sampson, David D.] Univ Western Australia, Opt Engn Lab, Nedlands, WA 6009, Australia. [Sampson, David D.] Univ Western Australia, Ctr Microscopy Characterisat & Anal, Nedlands, WA 6009, Australia. RP Villiger, M (reprint author), Harvard Univ, Sch Med, Boston, MA USA. EM mvilliger@mgh.harvard.edu NR 9 TC 0 Z9 0 U1 1 U2 3 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2374-0140 BN 978-1-4799-7465-8 J9 IEEE PHOTON CONF PY 2015 PG 2 WC Engineering, Electrical & Electronic; Optics SC Engineering; Optics GA BE3MN UT WOS:000370968200010 ER PT S AU Yao, RY Intes, X Fang, QQ AF Yao, Ruoyang Intes, Xavier Fang, Qianqian GP IEEE TI Re-tessellated Mesh-based Monte Carlo for Wide-Field Illumination Sources SO 2015 41ST ANNUAL NORTHEAST BIOMEDICAL ENGINEERING CONFERENCE (NEBEC) SE Annual IEEE Northeast Bioengineering Conference LA English DT Proceedings Paper CT 41st Annual Northeast Biomedical Engineering Conference (NEBEC) CY APR 17-19, 2015 CL Troy, NY ID TOMOGRAPHY; LIGHT AB Monte Carlo methods are the gold standard in modeling light propagation through complex turbid tissues. However, with the advent of structured light illumination applications, it is becoming crucial to implement fast and efficient methods to simulate arbitrary wide-field sources over large surface areas. Herein, we improve upon our previous mesh-based Monte Carlo method by enabling the simulation of an extended range of wide-field illumination strategies using a computationally efficient mesh re-tessellation technique. C1 [Yao, Ruoyang; Intes, Xavier] Rensselaer Polytech Inst, Dept Biomed Engn, 110 8th St, Troy, NY 12180 USA. [Fang, Qianqian] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Yao, RY (reprint author), Rensselaer Polytech Inst, Dept Biomed Engn, 110 8th St, Troy, NY 12180 USA. EM fangq@nmr.mgh.harvard.edu NR 13 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0277-1063 BN 978-1-4799-8360-5 J9 NORTHEAST BIOENGIN C PY 2015 PG 2 WC Engineering, Biomedical; Engineering, Electrical & Electronic SC Engineering GA BE3MX UT WOS:000370977700162 ER PT S AU Bluem, P Tonyushkin, A Deelchand, D Adriany, G Van de Moortele, PF Kiruluta, AJM Popovic, Z AF Bluem, Patrick Tonyushkin, Alexey Deelchand, Dinesh Adriany, Gregor Van de Moortele, Pierre-Francois Kiruluta, Andrew J. M. Popovic, Zoya GP IEEE TI Travelling-Wave Excitation for 16.4T Small-Bore MRI SO 2015 IEEE MTT-S INTERNATIONAL MICROWAVE SYMPOSIUM (IMS) SE IEEE MTT-S International Microwave Symposium LA English DT Proceedings Paper CT IEEE MTT-S International Microwave Symposium (IMS) CY MAY 17-22, 2015 CL Phoenix, AZ SP IEEE MTT S DE Magnetic Resonance Imaging; waveguide; travelling-wave; patch; circular polarization ID NMR; SPECTROSCOPY; ARRAY AB In this paper, we present the design of a probe for a travelling-wave 16.4T small-bore animal research MRI system. The probe is a 698-MHz coaxially-fed microstrip patch designed to give a circularly polarized magnetic field when placed in the bore cavity. Images of a water phantom using the patch probe are obtained and compared with simulations. Additionally, a periodic axial strip cylinder is inserted into the bore, resulting in a 7-fold increase in SNR, and enabling both gradient recalled echo and spin echo imaging of the phantom. The modified mode content in the image is compared to full-wave simulations. C1 [Bluem, Patrick; Popovic, Zoya] Univ Colorado, Boulder, CO 80309 USA. [Tonyushkin, Alexey; Kiruluta, Andrew J. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Deelchand, Dinesh; Adriany, Gregor; Van de Moortele, Pierre-Francois] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. RP Bluem, P (reprint author), Univ Colorado, Boulder, CO 80309 USA. RI Van de Moortele, Pierre-Francois/H-5087-2011; Adriany, Gregor/R-6656-2016 OI Van de Moortele, Pierre-Francois/0000-0002-6941-5947; NR 14 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0149-645X BN 978-1-4799-8275-2 J9 IEEE MTT S INT MICR PY 2015 PG 4 WC Computer Science, Theory & Methods; Engineering, Electrical & Electronic; Physics, Applied SC Computer Science; Engineering; Physics GA BE3HO UT WOS:000370722900172 ER PT B AU Chalino, MJ Wong, EYT Collins, BL Penson, RT AF Chalino, Mary J. Wong, Evelyn Y. T. Collins, Bradley L. Penson, Richard T. BA Surbone, A Rowe, M BF Surbone, A Rowe, M TI Psychological and existential consequences of medical error for oncology professionals SO CLINICAL ONCOLOGY AND ERROR REDUCTION LA English DT Article; Book Chapter ID SOCIAL RELATIONSHIPS; TREATMENT OUTCOMES; MENTAL-HEALTH; PHYSICIANS; BURNOUT; MORTALITY; COMMUNICATION; PERSPECTIVE; RESILIENCE; RESPONSES C1 [Chalino, Mary J.; Wong, Evelyn Y. T.; Collins, Bradley L.; Penson, Richard T.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Chalino, MJ (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. NR 86 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-74927-2; 978-1-118-74906-7 PY 2015 BP 29 EP 50 D2 10.1002/9781118749272 PG 22 WC Oncology SC Oncology GA BE2BJ UT WOS:000368912100005 ER PT B AU Shea, MEC Bohlen, N Lennes, IT AF Shea, Meghan E. C. Bohlen, Nie Lennes, Inga T. BA Surbone, A Rowe, M BF Surbone, A Rowe, M TI Prevention of errors and patient safety from the oncologist's perspective SO CLINICAL ONCOLOGY AND ERROR REDUCTION LA English DT Article; Book Chapter ID CANCER CARE; CHEMOTHERAPY; QUALITY; RADIATION C1 [Shea, Meghan E. C.] Harvard Univ, Sch Med, Div Hematol Oncol, Boston, MA USA. [Shea, Meghan E. C.; Lennes, Inga T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bohlen, Nie] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Lennes, Inga T.] Harvard Univ, Sch Med, Div Hematol Oncol, Clin Qual, Boston, MA USA. RP Shea, MEC (reprint author), Harvard Univ, Sch Med, Div Hematol Oncol, Boston, MA USA. NR 35 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-74927-2; 978-1-118-74906-7 PY 2015 BP 87 EP 100 D2 10.1002/9781118749272 PG 14 WC Oncology SC Oncology GA BE2BJ UT WOS:000368912100008 ER PT B AU Schapira, L Betancourt, JR Green, AR AF Schapira, Lidia Betancourt, Joseph R. Green, Alexander R. BA Surbone, A Rowe, M BF Surbone, A Rowe, M TI Do cross-cultural differences influence the occurrence and disclosure of medical errors in oncology? SO CLINICAL ONCOLOGY AND ERROR REDUCTION LA English DT Article; Book Chapter ID POPULATION-BASED ANALYSIS; RACIAL DISPARITIES; LUNG-CANCER; RACIAL/ETHNIC DISPARITIES; PHYSICIAN COMMUNICATION; ESOPHAGEAL CANCER; PATIENT SAFETY; SURVIVAL RATES; CARE; PATTERNS C1 [Schapira, Lidia] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. [Betancourt, Joseph R.; Green, Alexander R.] Massachusetts Gen Hosp, Dispar Solut Ctr, Boston, MA 02114 USA. RP Schapira, L (reprint author), Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. NR 38 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-74927-2; 978-1-118-74906-7 PY 2015 BP 111 EP 124 D2 10.1002/9781118749272 PG 14 WC Oncology SC Oncology GA BE2BJ UT WOS:000368912100010 ER PT J AU An, Q Han, C Zhou, YB Li, F Li, DL Zhang, XJ Yu, ZJ Duan, ZF Kan, QC AF An, Qi Han, Chao Zhou, Yubing Li, Feng Li, Duolu Zhang, Xiaojian Yu, Zujiang Duan, Zhenfeng Kan, Quancheng TI In vitro effects of mitomycin C on the proliferation of the non-small-cell lung cancer line A549 SO INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE LA English DT Article DE Mitomycin C; non-small-cell lung cancer (NSCLC); differentiation; cell cycle; retinoblastoma (Rb) gene ID ACUTE PROMYELOCYTIC LEUKEMIA; ACID-INDUCED DIFFERENTIATION; RETINOIC ACID; RETINOBLASTOMA PROTEIN; GENE-EXPRESSION; CYCLE CONTROL; APOPTOSIS; RB; INDUCTION; METAANALYSIS AB Non-small-cell lung cancer (NSCLC) is the leading cause of death from cancer in the United States. Chemotherapy prolongs survival among patients with advanced disease, but at the cost of clinically significant adverse effects. As a novel promising oncotherapy method, induced differentiation by mitomycin C has been applied for NSCLC therapy at recent year. In this study, the molecular mechanism of differentiation interruption by mitomycin C in the NSCLC line A549 was investigated. High dosage of mitomycin C (300 mu M) could significantly inhibit cell proliferation (P < 0.05) by 48.39 +/- 3.32% (P < 0.05), under which cell shrinkage and disruption were observed. Flow cytometry assay showed that the proportion of G1/G0 cells significantly increased, while that of S and G2/M cells significantly decreased after treatment of mitomycin C (10 or 300 mu M) for 24 h. These results indicated that cell arrest by mitomycin C appeared. Additionally, up-regulation of retinoblastoma (Rb) gene by low concentration of mitomycin C (10 mu M) was detected using immunohistochemistry (IHC) and Western blot assay, indicating a role in the regulation of cell cycle inhibition of this cell line. C1 [An, Qi; Han, Chao; Zhou, Yubing; Li, Feng; Li, Duolu; Zhang, Xiaojian; Kan, Quancheng] Zhengzhou Univ, Affiliated Hosp 1, Dept Clin Pharmacol, Zhengzhou 450052, Peoples R China. [Yu, Zujiang] Zhengzhou Univ, Affiliated Hosp 1, Dept Infect Dis, Zhengzhou 450052, Peoples R China. [Duan, Zhenfeng] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Sarcoma Biol Lab, Boston, MA 02114 USA. RP An, Q (reprint author), Zhengzhou Univ, Affiliated Hosp 1, Dept Clin Pharmacol, Zhengzhou 450052, Peoples R China. EM qi_an1024@163.com NR 36 TC 0 Z9 1 U1 0 U2 0 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 1940-5901 J9 INT J CLIN EXP MED JI Int. J. Clin. Exp. Med. PY 2015 VL 8 IS 11 BP 20516 EP 20523 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DF0FA UT WOS:000371013200079 PM 26884968 ER PT S AU Garg, S Brenner, MB AF Garg, Salil Brenner, Michael B. BE Platt, F Platt, N TI RNAi screens of lysosomal trafficking SO LYSOSOMES AND LYSOSOMAL DISEASES SE Methods in Cell Biology LA English DT Review; Book Chapter ID ANTIGEN PRESENTATION; GRISCELLI-SYNDROME; GTPASE ARL8B; MOLECULES; RAB27A; SECRETION; PATHWAYS; PROTEINS; LIPIDS; CD1B AB Here, we describe the general principles of RNA interference screens to study lysosomal functions in mammalian cells. Lysosomes occupy a central position in the biology of numerous processes such as degradation, microbial killing, and immunological antigen presentation to T cells. Selection of a screening system, conducting pooled versus arrayed screens, and appropriate steps in assay development, validation, and verification of novel gene candidates are all discussed. We focus on our experience in developing an arrayed short hairpin RNA screen to identify novel lysosomal trafficking proteins involved in vesicle and cargo trafficking and illustrate how such a trafficking library can be applied to screens involving lysosomes. C1 [Garg, Salil] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Garg, Salil] Harvard Univ, Sch Med, Harvard Combined Fellowship Mol Pathol, Boston, MA USA. [Brenner, Michael B.] Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, 75 Francis St, Boston, MA 02115 USA. RP Brenner, MB (reprint author), Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, 75 Francis St, Boston, MA 02115 USA. EM mbrenner@rics.bwh.harvard.edu FU NIAID NIH HHS [AI 063428, AI 28973] NR 25 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 SN 0091-679X BN 978-0-12-800079-3 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2015 VL 126 BP 119 EP 138 DI 10.1016/bs.mcb.2014.10.030 PG 20 WC Cell Biology SC Cell Biology GA BE3KI UT WOS:000370848600008 PM 25665444 ER PT J AU Fuehrlein, BS Cowell, AJ Pollio, D Cupps, L Balfour, ME North, CS AF Fuehrlein, Brian S. Cowell, Alexander J. Pollio, David Cupps, Lori Balfour, Margaret E. North, Carol S. TI A Prospective Study of the Associations Among Housing Status and Costs of Services in a Homeless Population SO PSYCHIATRIC SERVICES LA English DT Article ID SUBSTANCE USE; COMORBIDITY; DISORDERS; ALCOHOL; PROGRAM; ADULTS; WOMEN; TIME; CARE AB Objective: The complex needs of homeless populations result in use of a wide range of services and high costs for housing programs and psychiatric and general medical care. Allocation of resources often is not congruent with assessed needs. A series of cost-congruence hypotheses was developed to test assumptions that needs are associated with resources provided for appropriate services in homeless populations. Methods: Individuals (N=255) who were homeless were followed for two years and were categorized by housing status over time (consistently housed, housed late, lost housing, or consistently homeless). Detailed information about the individuals was obtained at baseline, and follow-up data were collected one and two years later. Extensive data about the costs of services provided by type (medical, psychiatric, substance abuse, and homeless maintenance and amelioration) were derived from 23 agencies, and service use information was collected from the agencies and by self-report. Multiple regression models were used to test the hypotheses. Results: Medical, psychiatric, and homeless maintenance costs varied by housing status. Serious mental illness predicted costs for psychiatric services, as expected, but also costs for substance abuse services and acute behavioral health care and total costs. Alcohol use disorders predicted substance abuse service costs. Conclusions: This study followed a homeless cohort prospectively and provided estimates of costs of service use derived from a large number of agencies. This research increases the understanding of patterns of service use in a homeless population and informs the provision of services appropriate to the complex needs of this difficult-to-serve population. C1 [Fuehrlein, Brian S.; Balfour, Margaret E.; North, Carol S.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. [North, Carol S.] US Dept Vet Affairs, North Texas Hlth Care Syst, Dallas, TX USA. [Cowell, Alexander J.] RTI Int, Dept Social Stat & Environm Sci, Res Triangle Pk, NC USA. [Pollio, David] Univ Alabama, Dept Social Work, Tuscaloosa, AL USA. [Cupps, Lori] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. RP Fuehrlein, BS (reprint author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA. EM fuehrlein@gmail.com OI Balfour, Margaret/0000-0002-1510-9709 FU National Institute on Drug Abuse [R01 DA10713] FX This work was funded by grant R01 DA10713 from the National Institute on Drug Abuse. NR 17 TC 2 Z9 2 U1 2 U2 5 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 EI 1557-9700 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD JAN PY 2015 VL 66 IS 1 BP 27 EP 32 DI 10.1176/appi.ps.201400010 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA DE3OD UT WOS:000370538700007 PM 25269783 ER PT J AU Roghmann, F Antczak, C McKay, RR Choueiri, T Hu, JC Kibel, AS Kim, SP Kowalczyk, KJ Menon, M Nguyen, PL Saad, F Sammon, JD Schmid, M Sukumar, S Sun, M Noldus, J Trinh, QD AF Roghmann, Florian Antczak, Carina McKay, Rana R. Choueiri, Toni Hu, Jim C. Kibel, Adam S. Kim, Simon P. Kowalczyk, Keith J. Menon, Mani Nguyen, Paul L. Saad, Fred Sammon, Jesse D. Schmid, Marianne Sukumar, Shyam Sun, Maxine Noldus, Joachim Quoc-Dien Trinh TI The burden of skeletal-related events in patients with prostate cancer and bone metastasis SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Skeletal-related event; NIS; Charges; Prostate cancer; Mortality ID POPULATION-BASED ANALYSIS; ZOLEDRONIC ACID; ANDROGEN-DEPRIVATION; UNITED-STATES; MEN; SURVIVAL; THERAPY; PLACEBO; CARE; MORTALITY AB Background: To assess contemporary characteristics, hospital admissions, charges, and mortality in patients with prostate cancer (CaP) who have hone metastases and skeletal-related events in an observational study. Methods: Relying on the Nationwide Inpatient Sample (NIS), patients with CaP with bone metastases between 1998 and 2010 were abstracted. Patients who experienced skeletal-related events were identified, and hospital charges were calculated. Generalized linear regression analyses focused on in-hospital mortality. Results: Between 1998 and 2010, a weighted estimate of 443,929 CaP visits with bone metastases was recorded. Of these, 15.9% experienced at least 1 SRE. The rate of SRE decreased from 18% to 15.4% (1998-2010, estimated annual percent change [EAPC] = -1.44%, P = 0.005) and the SRE-associated mortality decreased from 8.5% to 4.7% (1998-2010, EAPC = -3.68%, P = 0.004). Nevertheless, the inflation-adjusted charges associated with hospital visits of patients with CaP with bone metastases rose by 92% to $1,512,449,106 (EAPC = +8.82%, P < 0.001), and SRE charges rose by 94% to $369,256,799 (EAPC = +7.62%, P < 0.001). Predictors of in-hospital mortality in patients with SRE included age (odds ratio [OR] = 1.02), comorbidities (>= 3 vs. 0-1, OR = 1.72), SRE of the upper limb (OR = 1.75), SRE of the lower limb (OR = 1.35), spinal cord compression (OR = 1.48), radiation (OR = 0.68), surgery (OR = 0.32), and year of hospitalization (2010 vs. 1998, OR = 0.54; all P < 0.03). Conclusions: From 1998 to 2010, the incidence of SRE and SRE-associated mortality in patients with CaP and bone metastases decreased. However, charges for SRE-associated hospitalizations have increased alarmingly. Future health care policies should strive to provide cost-effective prevention and management of SREs in this population. (C) 2014 Elsevier Inc. All rights reserved. C1 [Roghmann, Florian; Noldus, Joachim] Ruhr Univ Bochum, Marien Hosp, Dept Urol, Herne, Germany. [Antczak, Carina; Sun, Maxine] Univ Montreal, Ctr Hlth, Canc Prognost & Hlth Outcomes Unit, Montreal, PQ, Canada. [McKay, Rana R.; Choueiri, Toni] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Oncol, Boston, MA 02115 USA. [Hu, Jim C.] Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA. [Kibel, Adam S.; Schmid, Marianne; Quoc-Dien Trinh] Harvard Univ, Sch Med, Div Urol Surg, Boston, MA 02115 USA. [Kibel, Adam S.; Schmid, Marianne; Quoc-Dien Trinh] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Kim, Simon P.] Yale Univ, Sch Med, Dept Urol, New Haven, CT USA. [Kowalczyk, Keith J.] Georgetown Univ Hosp, Dept Urol, Washington, DC 20007 USA. [Menon, Mani; Sammon, Jesse D.; Quoc-Dien Trinh] Henry Ford Hlth Syst, Vattikuti Urol Inst, Detroit, MI USA. [Nguyen, Paul L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Saad, Fred] Ctr Hosp Univ Montreal, CRCHUM, Montreal, PQ, Canada. [Sukumar, Shyam] Univ Minnesota, Dept Urol, Minneapolis, MN USA. RP Roghmann, F (reprint author), Ruhr Univ Bochum, Marien Hosp, Dept Urol, Herne, Germany. EM f.roghmann@gmail.com NR 28 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD JAN PY 2015 VL 33 IS 1 AR 17.e9 DI 10.1016/j.urolonc.2014.09.010 PG 10 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA DE9RH UT WOS:000370975300004 PM 25443265 ER PT J AU Ziehr, DR Mahal, BA Aizer, AA Hyatt, AS Beard, CJ D'Amico, AV Choueiri, TK Elfiky, A Lathan, CS Martin, NE Sweeney, CJ Trinh, QD Nguyen, PL AF Ziehr, David R. Mahal, Brandon A. Aizer, Ayal A. Hyatt, Andrew S. Beard, Clair J. D'Amico, Anthony V. Choueiri, Toni K. Elfiky, Aymen Lathan, Christopher S. Martin, Neil E. Sweeney, Christopher J. Quoc-Dien Trinh Nguyen, Paul L. TI Income inequality and treatment of African American men with high-risk prostate cancer SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE Prostate; Prostatic neoplasms; Health care disparities;Income; African Americans ID RADICAL PROSTATECTOMY; RACIAL-DIFFERENCES; RADIATION-THERAPY; MORTALITY; SURVIVAL AB Purpose: Definitive treatment of high-risk prostate cancer with radical prostatectomy or radiation improves survival. We assessed whether racial disparities in the receipt of definitive therapy for prostate cancer vary by regional income. Patients and methods: A cohort of 102,486 men (17,594 African American [AA] and 84,892 non-Hispanic white) with localized high risk prostate cancer (prostate-specific antigen >20 ng/ml or Gleason >= 8 or stage >= cT2c) diagnosed from 2004 to 2010 was identified in the Surveillance, Epidemiology, and End Results database. Income was measured at the census-tract-level. We used multivariable logistic regression to assess patient and cancer characteristics associated with the receipt of definitive therapy for prostate cancer. Multivariable Fine and Gray competing risks analysis was used to evaluate factors associated with prostate cancer death. Results: Overall, AA men were less likely to receive definitive therapy than white men (adjusted odds ratio [AOR] = 0.51; 95% CI: 0.49 0.54; P < 0.001), and there was a significant race/income interaction (P-interaction = 0.016) such that there was a larger racial treatment disparity in the bottom income quintile (AOR = 0.49; 95% CI: 0.45-0.55; P < 0.001) than in the top income quintile (AOR = 0.60; 95% CI: 0.51-0.71; P < 0.001). After a median follow-up of 35 months, AA men in the bottom income quintile suffered the greatest prostate cancer mortality (adjusted hazard ratio = 1.47; 95% CI: 1.17-1.84; P = 0.001), compared with white men in the top income quintile. Conclusions: Racial disparities in the receipt of definitive therapy for high-risk prostate cancer are greatest in low-income communities, suggesting that interventions to reduce racial disparities should target low-income populations first. (C) 2014 Elsevier Inc. All rights reserved. C1 [Ziehr, David R.; Mahal, Brandon A.] Harvard Univ, Sch Med, Boston, MA USA. [Aizer, Ayal A.] Harvard Radiat Oncol Program, Boston, MA USA. [Hyatt, Andrew S.; Beard, Clair J.; D'Amico, Anthony V.; Martin, Neil E.; Nguyen, Paul L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. [Hyatt, Andrew S.; Beard, Clair J.; D'Amico, Anthony V.; Choueiri, Toni K.; Elfiky, Aymen; Lathan, Christopher S.; Martin, Neil E.; Sweeney, Christopher J.; Nguyen, Paul L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Choueiri, Toni K.; Elfiky, Aymen; Lathan, Christopher S.; Sweeney, Christopher J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Quoc-Dien Trinh] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Urol, Boston, MA 02115 USA. RP Nguyen, PL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu FU Prostate Cancer Foundation, USA FX This work is supported by Fitz's Cancer Warriors, David and Cynthia Chapin, the Prostate Cancer Foundation, USA, Hugh Simons in honor of Frank and Anne Simons, and a grant from an anonymous family foundation. NR 33 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD JAN PY 2015 VL 33 IS 1 AR 18.e7 DI 10.1016/j.urolonc.2014.09.005 PG 7 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA DE9RH UT WOS:000370975300007 PM 25306287 ER PT J AU Gagnon, L Sakadzic, S Lesage, F Mandeville, ET Fang, QQ Yaseen, MA Boas, DA AF Gagnon, Louis Sakadzic, Sava Lesage, Frederic Mandeville, Emiri T. Fang, Qianqian Yaseen, Mohammad A. Boas, David A. TI Multimodal reconstruction of microvascular-flow distributions using combined two-photon microscopy and Doppler optical coherence tomography SO NEUROPHOTONICS LA English DT Article DE two-photon microscopy; optical coherence tomography; cerebral blood flow; multimodal imaging; microvasculature ID CEREBRAL-BLOOD-FLOW; IN-VIVO; NETWORKS; CORTEX; HEMODYNAMICS; METABOLISM; NEOCORTEX; COMPONENT; VESSELS; TISSUE AB Computing microvascular cerebral blood flow (mu CBF) in real cortical angiograms is challenging. Here, we investigated whether the use of Doppler optical coherence tomography (DOCT) flow measurements in individual vessel segments can help in reconstructing mu CBF across the entire vasculature of a truncated cortical angiogram. A mu CBF computational framework integrating DOCT measurements is presented. Simulations performed on a synthetic angiogram showed that the addition of DOCT measurements, especially close to large inflowing or outflowing vessels, reduces the impact of pressure boundary conditions and estimated vessel resistances resulting in a more accurate reconstruction of mu CBF. Our technique was then applied to reconstruct microvascular flow distributions in the mouse cortex down to 660 mu m by combining two-photon laser scanning microscopy angiography with DOCT. (C) 2015 Society of Photo-Optical Instrumentation Engineers (SPIE) C1 [Gagnon, Louis; Sakadzic, Sava; Mandeville, Emiri T.; Fang, Qianqian; Yaseen, Mohammad A.; Boas, David A.] Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Massachusetts Gen Hosp,Med Sch, Bldg 149 13th St, Charlestown, MA 02129 USA. [Gagnon, Louis; Boas, David A.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Gagnon, Louis; Lesage, Frederic] Ecole Polytech, Dept Elect Engn, Montreal, PQ H3T 1J4, Canada. RP Gagnon, L (reprint author), Harvard Univ, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Massachusetts Gen Hosp,Med Sch, Bldg 149 13th St, Charlestown, MA 02129 USA. EM lgagnon@nmr.mgh.harvard.edu FU NCRR NIH HHS [P41 RR014075]; NIA NIH HHS [R00 AG042026]; NIBIB NIH HHS [R01 EB021018, R01 EB000790]; NIDA NIH HHS [R90 DA023427]; NINDS NIH HHS [R01 NS057198, R01 NS057476, P01 NS055104, R00 NS067050] NR 35 TC 6 Z9 6 U1 1 U2 3 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 2329-423X EI 2329-4248 J9 NEUROPHOTONICS JI Neurophotonics PD JAN-MAR PY 2015 VL 2 IS 1 AR 015008 DI 10.1117/1.NPh.2.1.015008 PG 8 WC Neurosciences; Optics SC Neurosciences & Neurology; Optics GA DE3NO UT WOS:000370537000008 PM 26157987 ER PT J AU Magnain, C Augustinack, JC Konukoglu, E Frosch, MP Sakadzic, S Varjabedian, A Garcia, N Wedeen, VJ Boas, DA Fischl, B AF Magnain, Caroline Augustinack, Jean C. Konukoglu, Ender Frosch, Matthew P. Sakadzic, Sava Varjabedian, Ani Garcia, Nathalie Wedeen, Van J. Boas, David A. Fischl, Bruce TI Optical coherence tomography visualizes neurons in human entorhinal cortex SO NEUROPHOTONICS LA English DT Article DE histology; neuroanatomy; neurons; neuropathology; neurophotonics; optical coherence microscopy ID ALZHEIMERS-DISEASE; NEUROFIBRILLARY TANGLES; HUMAN BRAIN; FLUORESCENCE MICROSCOPY; CEREBRAL-CORTEX; MOUSE-BRAIN; CONTRAST; SCATTERING; PLAQUES; IMAGES AB The cytoarchitecture of the human brain is of great interest in diverse fields: neuroanatomy, neurology, neuroscience, and neuropathology. Traditional histology is a method that has been historically used to assess cell and fiber content in the ex vivo human brain. However, this technique suffers from significant distortions. We used a previously demonstrated optical coherence microscopy technique to image individual neurons in several square millimeters of en-face tissue blocks from layer II of the human entorhinal cortex, over 50 mu m in depth. The same slices were then sectioned and stained for Nissl substance. We registered the optical coherence tomography (OCT) images with the corresponding Nissl stained slices using a nonlinear transformation. The neurons were then segmented in both images and we quantified the overlap. We show that OCT images contain information about neurons that is comparable to what can be obtained from Nissl staining, and thus can be used to assess the cytoarchitecture of the ex vivo human brain with minimal distortion. With the future integration of a vibratome into the OCT imaging rig, this technique can be scaled up to obtain undistorted volumetric data of centimeter cube tissue blocks in the near term, and entire human hemispheres in the future. (C) 2015 Society of Photo-Optical Instrumentation Engineers (SPIE) C1 [Magnain, Caroline; Augustinack, Jean C.; Konukoglu, Ender; Sakadzic, Sava; Varjabedian, Ani; Garcia, Nathalie; Wedeen, Van J.; Boas, David A.; Fischl, Bruce] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Med Sch,Dept Radiol, 149 Thirteen St, Charlestown, MA 02129 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, Pathol Serv, CS Kubik Lab Neuropathol, Boston, MA 02115 USA. [Fischl, Bruce] MIT, Comp Sci & Al Lab, Stata Ctr, Cambridge, MA 02139 USA. RP Magnain, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Med Sch,Dept Radiol, 149 Thirteen St, Charlestown, MA 02129 USA. EM cmagnain@nmr.mgh.harvard.edu FU NCCIH NIH HHS [RC1 AT005728]; NCRR NIH HHS [S10 RR019307, S10 RR023043, S10 RR023401, U24 RR021382]; NIA NIH HHS [R01 AG022381, K01 AG028521, P50 AG005134, R01 AG008122, R01 AG016495]; NIBIB NIH HHS [P41 EB015896, R01 EB006758]; NIMH NIH HHS [U01 MH093765]; NINDS NIH HHS [R21 NS072652, P01 NS055104, R01 NS052585, R01 NS070963] NR 48 TC 10 Z9 10 U1 0 U2 7 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 2329-423X EI 2329-4248 J9 NEUROPHOTONICS JI Neurophotonics PD JAN-MAR PY 2015 VL 2 IS 1 AR UNSP 015004 DI 10.1117/1.NPh.2.1.015004 PG 8 WC Neurosciences; Optics SC Neurosciences & Neurology; Optics GA DE3NO UT WOS:000370537000004 PM 25741528 ER PT J AU Masha, L Zinchuk, A Boosalis, V AF Masha, Luke Zinchuk, Andrey Boosalis, Valia TI Synchronous pulmonary malignancies: atypical presentation of mantle cell lymphoma masking a lung malignancy SO RARE TUMORS LA English DT Article DE Lymphoma; pleural effusion; lung cancer; mantle cell ID CANCER AB We present a case of a pleural space malignancy masked by an atypical presentation of mantle cell lymphoma. Our patient presented with a large pleural effusion and right sided pleural studding, initially attributed to a new diagnosis of mantle cell lymphoma. Rare atypical epithelial cells were also seen amongst the clonal population of lymphocytes. The patient lacked systemic manifestations of mantle cell lymphoma and did not improve with chemotherapy. A pleural biopsy ultimately revealed the presence of an undifferentiated carcinoma, favoring a lung primary. A discussion of synchronous pleural space malignancies involving lymphomas is given. C1 [Masha, Luke] Boston Univ, Dept Internal Med, 72 East Concord St,Evans 124, Boston, MA 02118 USA. [Zinchuk, Andrey] Yale New Haven Med Ctr, Sect Pulm & Crit Care Med, 20 York St, New Haven, CT 06504 USA. [Boosalis, Valia] Boston VA Healthcare Syst, Sect Hematol Oncol, Boston, MA USA. RP Masha, L (reprint author), Boston Univ, Dept Internal Med, 72 East Concord St,Evans 124, Boston, MA 02118 USA. EM Luke.Masha@BMC.org OI Zinchuk, Andrey/0000-0003-0488-9778 NR 13 TC 0 Z9 0 U1 0 U2 0 PU PAGEPRESS PUBL PI PAVIA PA MEDITGROUP, VIA G BELLI, 4, PAVIA, 27100, ITALY SN 2036-3605 EI 2036-3613 J9 RARE TUMORS JI Rare Tumors PY 2015 VL 7 IS 3 BP 114 EP 116 AR 5929 DI 10.4081/rt.2015.5929 PG 3 WC Oncology SC Oncology GA DD8IL UT WOS:000370169700010 PM 26500732 ER PT J AU Ahmadi, F Oveisi, Z Samani, SM Amoozgar, Z AF Ahmadi, F. Oveisi, Z. Samani, S. Mohammadi Amoozgar, Z. TI Chitosan based hydrogels: characteristics and pharmaceutical applications SO RESEARCH IN PHARMACEUTICAL SCIENCES LA English DT Review DE Chitosan; Crosslinking; Drug delivery; Hydrogel; Tissue engineering ID TISSUE ENGINEERING APPLICATIONS; DRUG-DELIVERY APPLICATION; BIOMEDICAL APPLICATIONS; CONTROLLED-RELEASE; SODIUM ALGINATE; IN-VITRO; PHOTOCROSSLINKABLE CHITOSAN; VISCOELASTIC PROPERTIES; MUCOADHESIVE PROPERTIES; CARBOXYMETHYL CHITOSAN AB Hydrogel scaffolds serve as semi synthetic or synthetic extra cellular matrix to provide an amenable environment for cellular adherence and cellular remodeling in three dimensional structures mimicking that of natural cellular environment. Additionally, hydrogels have the capacity to carry small molecule drugs and/or proteins, growth factors and other necessary components for cell growth and differentiation. In the context of drug delivery, hydrogels can be utilized to localize drugs, increase drugs concentration at the site of action and consequently reduce off-targeted side effects. The current review aims to describe and classify hydrogels and their methods of production. The main highlight is chitosan-based hydrogels as biocompatible and medically relevant hydrogels for drug delivery. C1 [Ahmadi, F.; Oveisi, Z.; Samani, S. Mohammadi; Amoozgar, Z.] Shiraz Univ Med Sci, Sch Pharm, Dept Pharmaceut, Shiraz, Iran. [Amoozgar, Z.] Dana Farber Canc Inst, Dept Canc Immunol & Aids, Boston, MA 02115 USA. [Amoozgar, Z.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Amoozgar, Z (reprint author), Shiraz Univ Med Sci, Sch Pharm, Dept Pharmaceut, Shiraz, Iran. EM smsamani@sums.ac.ir; zohreh_amoozgar@dfci.harvard.edu RI Ahmadi, Fatemeh/K-1622-2013 NR 134 TC 6 Z9 7 U1 13 U2 23 PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD PI MUMBAI PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075, INDIA SN 1735-5362 EI 1735-9414 J9 RES PHARM SCI JI Res. Pharm. Sci. PY 2015 VL 10 IS 1 BP 1 EP 16 PG 16 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA DE2AN UT WOS:000370428700001 PM 26430453 ER PT J AU Kauf, TL Yang, JC Kimball, AB Sundaram, M Bao, YJ Okun, M Mulani, P Hauber, AB Johnson, FR AF Kauf, Teresa L. Yang, Jui-Chen Kimball, Alexa B. Sundaram, Murali Bao, Yanjun Okun, Martin Mulani, Parvez Hauber, A. Brett Johnson, F. Reed TI Psoriasis patients' willingness to accept side-effect risks for improved treatment efficacy SO JOURNAL OF DERMATOLOGICAL TREATMENT LA English DT Article DE Benefit-risk; discrete-choice experiment; maximum acceptable risk; psoriasis; risk tolerance; tumor necrosis factor blocker ID DISCRETE-CHOICE EXPERIMENT; CONJOINT-ANALYSIS; RHEUMATOID-ARTHRITIS; PLAQUE PSORIASIS; CROHNS-DISEASE; DRUG-TREATMENT; PREFERENCES; THERAPIES; BENEFITS; MODERATE AB Background: Previous studies suggest that efficacy is more important than side-effect risks to psoriasis patients. However, those studies did not consider potentially fatal risks of biologic treatments. Objective: To quantify the risks patients are willing to accept for improvements in psoriasis symptoms. Methods: Adults with a self-reported physician diagnosis of psoriasis were recruited through the National Psoriasis Foundation. Using a discrete-choice experiment, patients completed a series of nine choice questions, each including a pair of hypothetical treatments. Treatments were defined by severity of plaques, body surface area (BSA), and 10-year risks of tuberculosis, serious infection and lymphoma. Results: For complete clearance of 25% BSA with mild plaques, respondents (n = 1608) were willing to accept a 20% (95% confidence interval: 9-26%) risk of serious infection, 10% (5-15%) risk of tuberculosis and 2% (1-3%) risk of lymphoma. For complete clearance of 25% BSA with severe plaques, respondents were willing to accept a 54% (48-62%) risk of serious infection, 36% (28-49%) risk of tuberculosis and 8% (7-9%) risk of lymphoma. Limitations: Respondents were asked to evaluate hypothetical scenarios. Actual treatment choices may differ. Conclusion: Respondents were willing to accept risks above likely clinical exposures for improvements in psoriasis symptoms. Individual risk tolerances may vary. C1 [Hauber, A. Brett] RTI Hlth Solut, 200 Pk Off Dr,POB 12194, Res Triangle Pk, NC 27709 USA. [Kauf, Teresa L.] Cubist Pharmaceut, Lexington, MA USA. [Yang, Jui-Chen] Pacific Econ Res LLC, Bellevue, WA USA. [Kimball, Alexa B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sundaram, Murali; Bao, Yanjun; Okun, Martin; Mulani, Parvez] AbbVie Inc, N Chicago, IL USA. [Johnson, F. Reed] Duke Clin Res Inst, Ctr Clin & Genet Econ, Durham, NC USA. RP Hauber, AB (reprint author), RTI Hlth Solut, 200 Pk Off Dr,POB 12194, Res Triangle Pk, NC 27709 USA. EM abhauber@rti.org FU AbbVie; RTI Health Solutions; Janssen FX Johnson, Yang and Hauber were employees of RTI Health Solutions at the time this study was conducted. Kauf was an employee of the University of Florida at the time of the study. Kauf received research contracts from RTI Health Solutions, Novartis, and GlaxoSmithKline at the time this research was conducted. This study was funded by AbbVie through a research contract with RTI Health Solutions.; Kimball has served as consultant and/or investigator to AbbVie, Amgen and Janssen, and received grants and/or fellowship from Janssen. NR 31 TC 3 Z9 3 U1 2 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0954-6634 EI 1471-1753 J9 J DERMATOL TREAT JI J. Dermatol. Treat. PY 2015 VL 26 IS 6 BP 507 EP 513 DI 10.3109/09546634.2015.1034071 PG 7 WC Dermatology SC Dermatology GA DD5JP UT WOS:000369960000004 PM 25946139 ER PT J AU Liu, YN Magro, C Loewenstein, JI Makar, RS Stowell, CP Dzik, WH Hochberg, EP Oaklander, AL Sobrin, L AF Liu, Yingna Magro, Cynthia Loewenstein, John I. Makar, Robert S. Stowell, Christopher P. Dzik, Walter H. Hochberg, Ephraim P. Oaklander, Anne Louise Sobrin, Lucia TI A Man with Paraneoplastic Retinopathy plus Small Fiber Polyneuropathy Associated with Waldenstrom Macroglobulinemia (Lymphoplasmacytic Lymphoma): Insights into Mechanisms SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Letter DE Autoimmune retinopathy; cancer-associated retinopathy; plasmapheresis; paraneoplastic retinopathy; rituximab ID CANCER-ASSOCIATED RETINOPATHY AB Purpose: To report a well-characterized Waldenstrom's macroglobulinemia (WM) case that provides insight into the mechanisms of two paraneoplastic complications - cancer-associated retinopathy (CAR) and small fiber polyneuropathy (SFPN). Methods: Retrospective medical chart review. Results: A 58-year old man with WM developed vision loss and bilateral lower extremity pain. CAR was diagnosed by history, a depressed electroretinogram (ERG) and positive anti-retinal antibodies. SFPN diagnosis was based on abnormal autonomic nerve function testing and a distal-leg skin biopsy that demonstrated absent epidermal small-fiber innervation, IgM and complement deposition and microvasculopathy. Plasma exchange (PLEX) led to dramatic pain relief and subjective improvement in eye symptoms along with improvement of some ERG parameters. Repeat skin biopsy after treatment showed less microvascular abnormalities and decreased complement deposition. Conclusions: The concurrence of CAR and SFPN in this patient suggest that both were complications of WM and their common response to PLEX suggests co-mediation by humoral factors that accessed target antigens through IgM-triggered, complement-mediated vascular damage. C1 [Liu, Yingna; Loewenstein, John I.; Sobrin, Lucia] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Magro, Cynthia] Cornell Univ, Dept Pathol & Lab Med, Weill Cornell Med Coll, New York, NY 10021 USA. [Makar, Robert S.; Stowell, Christopher P.; Dzik, Walter H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,Blood Transfus Serv, Boston, MA 02114 USA. [Hochberg, Ephraim P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Oncol, Boston, MA 02114 USA. [Oaklander, Anne Louise] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Oaklander, Anne Louise] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol Neuropathol, Boston, MA 02114 USA. RP Sobrin, L (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Ophthalmol,Uveitis Serv, 243 Charles St,12th Floor, Boston, MA 02114 USA.; Sobrin, L (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Ophthalmol,Retina Serv, 243 Charles St,12th Floor, Boston, MA 02114 USA. EM Lucia_sobrin@meei.harvard.edu NR 13 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0927-3948 EI 1744-5078 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PY 2015 VL 23 IS 5 BP 405 EP 409 DI 10.3109/09273948.2014.884599 PG 5 WC Ophthalmology SC Ophthalmology GA DD3JY UT WOS:000369819700008 PM 24654565 ER PT J AU Stacy, RC Uchiyama, E Jakobiec, FA Sobrin, L AF Stacy, Rebecca C. Uchiyama, Eduardo Jakobiec, Frederick A. Sobrin, Lucia TI Posterior Necrotizing Scleritis Presenting as Sectoral Chorioretinitis SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Letter ID IMMUNOPATHOLOGY; DISEASE C1 [Stacy, Rebecca C.; Uchiyama, Eduardo; Jakobiec, Frederick A.; Sobrin, Lucia] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Stacy, Rebecca C.; Uchiyama, Eduardo; Jakobiec, Frederick A.; Sobrin, Lucia] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Stacy, RC (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Rebecca_Stacy@meei.harvard.edu NR 11 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0927-3948 EI 1744-5078 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PY 2015 VL 23 IS 5 BP 412 EP 415 DI 10.3109/09273948.2014.896467 PG 4 WC Ophthalmology SC Ophthalmology GA DD3JY UT WOS:000369819700010 PM 24654986 ER PT S AU Selej, M Romero, AJ Channick, RN Clozel, M AF Selej, Mona Romero, Alain J. Channick, Richard N. Clozel, Martine GP NY Acad Sci TI Development of macitentan for the treatment of pulmonary arterial hypertension SO PHARMACEUTICAL SCIENCE TO IMPROVE THE HUMAN CONDITION: PRIX GALIEN 2014 SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE macitentan; endothelin; pulmonary arterial hypertension; SERAPHIN; drug development ID ENDOTHELIN RECEPTOR ANTAGONIST; 6-MINUTE WALK DISTANCE; NITRIC-OXIDE SYNTHASE; SMOOTH-MUSCLE-CELLS; HEALTHY-SUBJECTS; END-POINTS; ET(B) RECEPTORS; ETB RECEPTORS; IN-VIVO; EXPRESSION AB Pulmonary arterial hypertension (PAH) is a serious, chronic condition that, without early recognition and treatment, leads to progressive right heart failure and death. The dual endothelin receptor antagonist macitentan was designed through a deliberate discovery process to maximize endothelin-axis blockade while improving adverse -effect profiles compared with previous compounds. Macitentan's efficacy was demonstrated in an event-driven morbidity and mortality study of treatment -naive and background PAH therapy treated symptomatic patients. Compared to placebo, 10 mg of macitentan significantly reduced the relative risk of morbidity and mortality by 45%, primarily by delaying PAH worsening, most prominently in World Health Organization (WHO) functional class II and III PAH patients. Macitentan reduced the incidence of the composite end point of PAH-related hospitalizations and mortality and improved WHO FC and exercise capacity (6-min walk distance). Furthermore, it significantly improved cardiopulmonary hemo dynamics and quality of life, and had a favorable safety and tolerability profile. To date, this was the largest and longest prospective trial for PAH. Macitentan, currently the only approved oral PAH treatment shown to be safe and effective in delaying long-term progression and reducing PAH-related hospitalizations, has changed treatment paradigms from goal-directed to long-term outcome oriented therapy. C1 [Selej, Mona; Romero, Alain J.] Actel Pharmaceut US Inc, San Francisco, CA USA. [Channick, Richard N.] Massachusetts Gen Hosp, Pulm & Crit Care, Boston, MA 02114 USA. [Clozel, Martine] Actel Pharmaceut Ltd, Allschwil, Switzerland. RP Selej, M (reprint author), Actel Pharmaceut US Inc, Med Affairs ERA Franchise, 5000 Shoreline Ct,Suite 200, San Francisco, CA 94080 USA. EM mona.selej@actelion.com NR 97 TC 0 Z9 1 U1 1 U2 1 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 2015 VL 1358 BP 68 EP 81 DI 10.1111/nyas.12856 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BE2SY UT WOS:000369996200006 PM 26291180 ER PT J AU Cheng, R Azarbal, A Currier, J Thomson, LEJ Hamilton, MA Esmailian, F Azarbal, B AF Cheng, Richard Azarbal, Amir Currier, Jesse Thomson, Louise E. J. Hamilton, Michele A. Esmailian, Fardad Azarbal, Babak TI Tricuspid Regurgitation, the Forgotten Valvular Lesion-A Contemporary Review of Etiology, Prevalence, and Management Options SO REVIEWS IN CARDIOVASCULAR MEDICINE LA English DT Review DE Tricuspid regurgitation; Tricuspid valve disease; Cardiac surgery; Valvular heart disease ID IN-VALVE IMPLANTATION; DOPPLER COLOR-FLOW; HEART-TRANSPLANTATION; FOLLOW-UP; REPLACEMENT; REPAIR; DISEASE; SURGERY; PREDICTORS; STENOSIS AB Tricuspid regurgitation (TR) is a common finding. Pathologic TR is an independent risk factor for mortality. TR can be classified by etiology into functional versus organic. Organic TR is caused by structural damage to the tricuspid valve (TV) by a spectrum of etiologies, including pacemaker leads and right heart biopsies, whereas functional TR is predominantly due to elevated pulmonary pressures. Atrial fibrillation and chamber enlargement, among other risk factors, are strong predictors of functional TR. Correction of elevated pulmonary pressures improves TR, and concurrent repair of severe TR at the time of left heart valve surgery improves postoperative heart failure symptoms but does not improve survival. TR repair is associated with less operative and long-term mortality than TV replacement, and demonstrates similar improvements in heart failure symptoms. Substantial residual TR remains after repair, and reoperative mortality for residual TR is considerable. Percutaneous TV replacement may offer a rescue strategy. (C) 2015 MedReviews (R), LLC C1 [Cheng, Richard; Thomson, Louise E. J.; Hamilton, Michele A.; Esmailian, Fardad; Azarbal, Babak] Cedars Sinai Heart Inst, Los Angeles, CA USA. [Azarbal, Amir] Univ Alabama, Med Ctr, Dept Med, Huntsville, AL 35899 USA. [Currier, Jesse; Azarbal, Babak] VA Greater Los Angeles Healthcare Syst, Div Cardiol, Los Angeles, CA USA. RP Cheng, R (reprint author), Cedars Sinai Heart Inst, Los Angeles, CA USA. OI Cheng, Richard/0000-0003-2552-6773 NR 56 TC 1 Z9 1 U1 0 U2 0 PU MEDREVIEWS, LLC PI NEW YORK PA 1370 BROADWAY, STE 900, NEW YORK, NY 10018 USA SN 1530-6550 EI 2153-8174 J9 REV CARDIOVASC MED JI Rev. Cardiovasc. Med. PY 2015 VL 16 IS 3 BP 171 EP 181 DI 10.3909/ricm0766 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DD2TM UT WOS:000369775100001 PM 26451764 ER PT J AU Anastasides, N Beck, KD Pang, KCH Servatius, RJ Gilbertson, MW Orr, SP Myers, CE AF Anastasides, Nicole Beck, Kevin D. Pang, Kevin C. H. Servatius, Richard J. Gilbertson, Mark W. Orr, Scott P. Myers, Catherine E. TI Increased generalization of learned associations is related to re-experiencing symptoms in veterans with symptoms of post-traumatic stress SO STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS LA English DT Article DE Anxiety; associative learning; declarative memory; stress; transfer; veterans ID BEHAVIORALLY INHIBITED TEMPERAMENT; DISORDER; MEMORY; PTSD; HIPPOCAMPAL AB One interpretation of re-experiencing symptoms in post-traumatic stress disorder (PTSD) is that memories related to emotional information are stored strongly, but with insufficient specificity, so that stimuli which are minimally related to the traumatic event are sufficient to trigger recall. If so, re-experiencing symptoms may reflect a general bias against encoding background information during a learning experience, and this tendency might not be limited to learning about traumatic or even autobiographical events. To test this possibility, we administered a discrimination-and-transfer task to 60 Veterans (11.2% female, mean age 54.0 years) self-assessed for PTSD symptoms in order to examine whether re-experiencing symptoms were associated with increased generalization following associative learning. The discrimination task involved learning to choose the rewarded object from each of six object pairs; each pair differed in color or shape but not both. In the transfer phase, the irrelevant feature in each pair was altered. Regression analysis revealed no relationships between re-experiencing symptoms and initial discrimination learning. However, re-experiencing symptom scores contributed to the prediction of transfer performance. Other PTSD symptom clusters (avoidance/numbing, hyperarousal) did not account for significant additional variance. The results are consistent with an emerging interpretation of re-experiencing symptoms as reflecting a learning bias that favors generalization at the expense of specificity. Future studies will be needed to determine whether this learning bias may pre-date and confer risk for, re-experiencing symptoms in individuals subsequently exposed to trauma, or emerges only in the wake of trauma exposure and PTSD symptom development. C1 [Anastasides, Nicole; Beck, Kevin D.; Pang, Kevin C. H.; Myers, Catherine E.] VA New Jersey Hlth Care Syst, Dept Vet Affairs, E Orange, NJ 07018 USA. [Beck, Kevin D.; Pang, Kevin C. H.; Servatius, Richard J.; Myers, Catherine E.] Rutgers State Univ, Dept Pharmacol Physiol & Neurosci, New Jersey Med Sch, Newark, NJ 07102 USA. [Servatius, Richard J.] Syracuse VA Med Ctr, Dept Vet Affairs, Syracuse, NY USA. [Gilbertson, Mark W.] Manchester VA Med Ctr, Dept Vet Affairs, Manchester, NH USA. [Orr, Scott P.] Harvard Univ, Sch Med, Boston, MA USA. [Orr, Scott P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Anastasides, N (reprint author), VA New Jersey Hlth Care Syst, NeuroBehav Res Lab, 385 Tremont Ave,Mail Stop 15a, E Orange, NJ 07018 USA. EM nicole.anastasides@va.gov FU NSF/NIH Collaborative Research in Computational Neuroscience (CRCNS) program; NIAAA [R01 AA018737]; Clinical Science Research and Development Service of the VA Office of Research and Development [I01CX000771]; SMBI FX This work was supported by the NSF/NIH Collaborative Research in Computational Neuroscience (CRCNS) program and NIAAA R01 AA018737, by Award Number I01CX000771 from the Clinical Science Research and Development Service of the VA Office of Research and Development, and by the SMBI. The authors affirm that they have no relationships that could constitute potential conflict of interest. NR 28 TC 4 Z9 4 U1 2 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1025-3890 EI 1607-8888 J9 STRESS JI Stress PY 2015 VL 18 IS 4 BP 484 EP 489 DI 10.3109/10253890.2015.1053450 PG 6 WC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences SC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences & Neurology GA DD3KU UT WOS:000369821900012 PM 26372003 ER PT B AU Pong, T Huang, PL AF Pong, Terrence Huang, Paul L. BE Wang, H Patterson, C Pratico, D Jain, MK Yang, X Sibinga, NES Feinberg, MW TI EFFECTS OF NITRIC OXIDE ON ATHEROSCLEROSIS SO ATHEROSCLEROSIS: RISKS, MECHANISMS, AND THERAPIES LA English DT Article; Book Chapter ID LOW-DENSITY-LIPOPROTEIN; DOUBLE-KNOCKOUT MICE; PROTEIN-KINASE AKT; ENDOTHELIAL DYSFUNCTION; SHEAR-STRESS; ACCELERATED ATHEROSCLEROSIS; SUPEROXIDE-PRODUCTION; SYNTHASE EXPRESSION; PRESSURE-OVERLOAD; VASCULAR-DISEASE C1 [Pong, Terrence] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Huang, Paul L.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Huang, Paul L.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Huang, Paul L.] Harvard Univ, Sch Med, Boston, MA USA. RP Pong, T (reprint author), Univ Calif San Francisco, Sch Med, San Francisco, CA USA. NR 55 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-82853-3; 978-1-118-28591-6 PY 2015 BP 355 EP 364 D2 10.1002/9781118828533 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA BE2JJ UT WOS:000369411200030 ER PT B AU Thukkani, AK Jaffer, FA AF Thukkani, Arun K. Jaffer, Farouc A. BE Wang, H Patterson, C Pratico, D Jain, MK Yang, X Sibinga, NES Feinberg, MW TI MOLECULAR IMAGING SO ATHEROSCLEROSIS: RISKS, MECHANISMS, AND THERAPIES LA English DT Article; Book Chapter ID POSITRON-EMISSION-TOMOGRAPHY; ULTRASMALL SUPERPARAMAGNETIC PARTICLES; HUMAN ATHEROSCLEROTIC PLAQUES; ABDOMINAL AORTIC-ANEURYSMS; VASCULAR F-18-FDG UPTAKE; ACUTE CORONARY SYNDROME; IRON-OXIDE; IN-VIVO; CARDIOVASCULAR-DISEASE; VULNERABLE PLAQUE C1 [Thukkani, Arun K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. [Jaffer, Farouc A.] Harvard Univ, Sch Med, Dept Med, Cardiovasc Res Ctr,Cardiol Div,Massachusetts Gen, Boston, MA USA. [Jaffer, Farouc A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. RP Thukkani, AK (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. NR 50 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-118-82853-3; 978-1-118-28591-6 PY 2015 BP 503 EP 516 D2 10.1002/9781118828533 PG 14 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA BE2JJ UT WOS:000369411200041 ER PT J AU Rao, BB Click, B Eid, G Codario, RA AF Rao, Bhavana B. Click, Benjamin Eid, George Codario, Ronald A. TI Management of Refractory Noninsulinoma Pancreatogenous Hypoglycemia Syndrome with Gastric Bypass Reversal: A Case Report and Review of the Literature SO CASE REPORTS IN ENDOCRINOLOGY LA English DT Review ID HYPERINSULINEMIC HYPOGLYCEMIA; SURGERY AB Background. Roux-en-Y gastric bypass (RYGB) is a commonly performed, effective bariatric procedure; however, rarely, complications such as postprandial hypoglycemia due to noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS) may ensue. Management of refractory NIPHS is challenging. We report a case that was successfully treated with RYGB reversal. Case Report. A 58-year-old male with history of RYGB nine months earlier for morbid obesity presented for evaluation of postprandial, hypoglycemic seizures. Testing for insulin level, insulin antibodies, oral hypoglycemic agents, pituitary axis hormone levels, and cortisol stimulation was unrevealing. Computed tomography (CT) scan of the abdomen was unremarkable. A 72-hour fast was completed without hypoglycemia. Mixed meal testing demonstrated endogenous hyperinsulinemic hypoglycemia (EHH) and selective arterial calcium stimulation testing (SACST) was positive. Strict dietary modifications, maximal medical therapy, gastrostomy tube feeding, and stomal reduction failed to alleviate symptoms. Ultimately, he underwent laparoscopic reversal of RYGB. Now, 9 months after reversal, he has markedly reduced hypoglycemia burden. Discussion. Hyperfunctioning islets secondary to exaggerated incretin response and altered intestinal nutrient delivery are hypothesized to be causative in NIPHS. For refractory cases, there is increasing skepticism about the safety and efficacy of pancreatic resection. RYGB reversal may be successful. C1 [Rao, Bhavana B.; Click, Benjamin] Univ Pittsburgh, Med Ctr, Dept Internal Med, Pittsburgh, PA 15213 USA. [Eid, George] Allegheny Hlth Network, Div Bariatr Surg, Pittsburgh, PA 15212 USA. [Codario, Ronald A.] VA Pittsburgh Healthcare Syst, Div Endocrinol, Dept Internal Med, Pittsburgh, PA 15240 USA. RP Codario, RA (reprint author), VA Pittsburgh Healthcare Syst, Div Endocrinol, Dept Internal Med, Pittsburgh, PA 15240 USA. EM ronald.codario@va.gov NR 10 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-6501 EI 2090-651X J9 CASE REP ENDOCRINOL JI Case Rep. Endocrinol. PY 2015 AR 384526 DI 10.1155/2015/384526 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DD1DU UT WOS:000369662200001 ER PT S AU Torrado-Carvajal, A Alcain, E Montemayor, S Herraiz, JL Rozenholc, Y Hernandez-Tamames, JA Adalsteinsson, E Wald, LL Malpica, N AF Torrado-Carvajal, A. Alcain, E. Montemayor, S. Herraiz, J. L. Rozenholc, Y. Hernandez-Tamames, J. A. Adalsteinsson, E. Wald, L. L. Malpica, N. BE Romero, E Lepore, N GarciaArteaga, JD Brieva, J TI Fast pseudo-CT synthesis from MRI T1-weighted images using a patch-based approach SO 11TH INTERNATIONAL SYMPOSIUM ON MEDICAL INFORMATION PROCESSING AND ANALYSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT 11th International Symposium on Medical Information Processing and Analysis (SIPAIM) CY NOV 17-19, 2015 CL Cuenca, ECUADOR SP Univ Nacl Colombia, Univ Politecnica Salesiana, Univ Cuenca, Prometeo - Secretaria Educac Super, Ciencia, Tecnologia & Innovac, Univ Nacl Colombia Sede Bogota, CIM@lab, Red Nacl Investigac &Educac Ecuador DE Bone detection; GPU processing; modality propagation; patch-based; pseudo-CT ID ATTENUATION CORRECTION; SEGMENTATION; SKULL; MODEL AB MRI-based bone segmentation is a challenging task because bone tissue and air both present low signal intensity on MR images, making it difficult to accurately delimit the bone boundaries. However, estimating bone from MRI images may allow decreasing patient ionization by removing the need of patient-specific CT acquisition in several applications. In this work, we propose a fast GPU-based pseudo-CT generation from a patient-specific MRI T1-weighted image using a group-wise patch-based approach and a limited MRI and CT atlas dictionary. For every voxel in the input MR image, we compute the similarity of the patch containing that voxel with the patches of all MR images in the database, which lie in a certain anatomical neighborhood. The pseudo-CT is obtained as a local weighted linear combination of the CT values of the corresponding patches. The algorithm was implemented in a GPU. The use of patch-based techniques allows a fast and accurate estimation of the pseudo-CT from MR T1-weighted images, with a similar accuracy as the patient-specific CT. The experimental normalized cross correlation reaches 0.9324 +/- 0.0048 for an atlas with 10 datasets. The high NCC values indicate how our method can accurately approximate the patient-specific CT. The GPU implementation led to a substantial decrease in computational time making the approach suitable for real applications. C1 [Torrado-Carvajal, A.; Hernandez-Tamames, J. A.; Malpica, N.] Univ Rey Juan Carlos, Med Image Anal & Biometry Lab, Madrid, Spain. [Torrado-Carvajal, A.; Herraiz, J. L.; Hernandez-Tamames, J. A.; Adalsteinsson, E.; Wald, L. L.; Malpica, N.] Madrid MIT M Vis Consortium, Madrid, Spain. [Alcain, E.; Montemayor, S.] Univ Rey Juan Carlos, Dept Comp Sci, Madrid, Spain. [Herraiz, J. L.] MIT, Res Lab Elect, Cambridge, MA 02139 USA. [Rozenholc, Y.] Univ Paris 05, MAPS, CNRS, UMR 8145, Paris, France. [Adalsteinsson, E.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Adalsteinsson, E.] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA. [Adalsteinsson, E.; Wald, L. L.] MIT, Harvard MIT Hlth Sci & Technol, Cambridge, MA 02139 USA. [Wald, L. L.] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Torrado-Carvajal, A (reprint author), Univ Rey Juan Carlos, Med Image Anal & Biometry Lab, Madrid, Spain. RI Wald, Lawrence/D-4151-2009; Hernandez-Tamames, Juan /N-5319-2014; LOPEZ HERRAIZ, JOAQUIN/E-9234-2010 OI Hernandez-Tamames, Juan /0000-0003-0027-9518; LOPEZ HERRAIZ, JOAQUIN/0000-0001-7208-8863 NR 15 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-916-0 J9 PROC SPIE PY 2015 VL 9681 AR 968106 DI 10.1117/12.2210963 PG 7 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BE2CW UT WOS:000369010400006 ER PT J AU Jovanovich, AJ Chonchol, MB Sobhi, A Kendrick, JB Cheung, AK Kaufman, JS Smits, G Jablonski, KL AF Jovanovich, Anna J. Chonchol, Michel B. Sobhi, Atousa Kendrick, Jessica B. Cheung, Alfred K. Kaufman, James S. Smits, Gerard Jablonski, Kristen L. CA HOST Investigators TI Mineral Metabolites, Angiotensin II Inhibition and Outcomes in Advanced Chronic Kidney Disease SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Dialysis; Mortality; Phosphorus; Renin-angiotensin inhibition ID STAGE RENAL-DISEASE; RANDOMIZED CONTROLLED-TRIAL; CONVERTING ENZYME-INHIBITORS; LONG-TERM HEMODIALYSIS; CARDIOVASCULAR OUTCOMES; ALDOSTERONE SYSTEM; RECEPTOR BLOCKERS; ACE-INHIBITORS; MORTALITY RISK; HEART-FAILURE AB Background: Evidence suggests that the renin angiotensin aldosterone system (RAAS) interacts with the vitamin D-fibroblast growth factor 23-Klotho axis. We investigated whether circulating mineral metabolism markers modify outcomes in response to RAAS inhibition in subjects with advanced chronic kidney disease (CKD). Methods: In this retrospective cohort study, we analyzed the association of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) use with all-cause mortality and dialysis initiation among 1,753 subjects (1,099 CKD, estimated glomerular filtration rate 18 +/- 6 ml/min/1.73 m(2) and 654 end-stage renal disease [ESRD]) from the Homocysteine in Kidney and End Stage Renal Disease (HOST) study. A propensity score analysis accounted for indication bias and Cox re-gression models adjusted for mineral metabolism markers. Results: Mean follow-up was 3.2 years; 714 (41%) subjects died and 615 (56%) initiated dialysis. In adjusted analyses, all subjects treated with ACEI/ARB had a significantly lower hazard of death (hazards ratio (HR) 0.81, 95% CI 0.70-0.95, p = 0.007). Those with CKD not on dialysis and treated with ACEI/ARB trended toward a lower hazard of dialysis initiation (HR 0.86, 95% CI 0.73-1.01, p = 0.06). The association with mortality did not differ by level of mineral metabolism marker (p for interaction >0.16); however, the relationship with dialysis initiation differed according to the median serum phosphorus level (p for interaction <0.001). Conclusions: RAAS inhibition was associated with decreased all-cause mortality independent of disordered mineral metabolism among mostly male HOST subjects with advanced CKD and ESRD. However, among those with CKD not requiring dialysis, the renoprotection associated with RAAS inhibition was attenuated by higher serum phosphorus levels. Further studies are needed to confirm this association. (C) 2015 S. Karger AG, Basel C1 [Jovanovich, Anna J.; Chonchol, Michel B.; Kendrick, Jessica B.; Smits, Gerard; Jablonski, Kristen L.] Univ Colorado Denver, Div Renal Dis & Hypertens, Mail Stop C281,13199 E Montview Blvd,Ste 495, Aurora, CO 80010 USA. [Jovanovich, Anna J.] Denver Vet Affairs Med Ctr, Med Serv, Renal Sect, Denver, CO USA. [Sobhi, Atousa] Univ Colorado, Sch Med, Denver, CO USA. [Kendrick, Jessica B.] Denver Hlth Med Ctr, Div Renal, Denver, CO USA. [Cheung, Alfred K.] Univ Utah, Div Nephrol & Hypertens, Salt Lake City, UT USA. [Cheung, Alfred K.] Vet Affairs Salt Lake City Healthcare Syst, Med Serv, Renal Sect, Salt Lake City, UT USA. [Kaufman, James S.] Vet Affairs NY Harbor Healthcare Syst, Med Serv, Renal Sect, New York, NY USA. [Kaufman, James S.] NYU, Langone Med Ctr, New York, NY USA. RP Jovanovich, AJ (reprint author), Univ Colorado Denver, Div Renal Dis & Hypertens, Mail Stop C281,13199 E Montview Blvd,Ste 495, Aurora, CO 80010 USA. EM anna.jovanovich@ucdenver.edu FU HOST executive Committee; Department of Veterans Affairs Cooperative Studies Program; American Heart Association [12POST11920023]; VA Career Development Award 2 [1IKCX001030-01A1] FX This study was supported by the HOST executive Committee and the Department of Veterans Affairs Cooperative Studies Program, by the American Heart Association (12POST11920023) and by a VA Career Development Award 2 (1IKCX001030-01A1). There are no conflicts of interest to report. NR 36 TC 1 Z9 1 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 EI 1421-9670 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2015 VL 42 IS 5 BP 361 EP 368 DI 10.1159/000441684 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA DB9VC UT WOS:000368864800003 PM 26606453 ER PT J AU Dahl, R Calverley, PMA Anzueto, A Metzdorf, N Fowler, A Mueller, A Wise, R Dusser, D AF Dahl, Ronald Calverley, Peter M. A. Anzueto, Antonio Metzdorf, Norbert Fowler, Andy Mueller, Achim Wise, Robert Dusser, Daniel TI Safety and efficacy of tiotropium in patients switching from HandiHaler to Respimat in the TIOSPIR trial SO BMJ OPEN LA English DT Article DE Tiotropium; COPD; Respimat (R); HandiHaler (R); Switching; Efficacy ID OBSTRUCTIVE PULMONARY-DISEASE; RANDOMIZED CONTROLLED-TRIALS; CLINICAL-TRIALS; MIST INHALER; MORTALITY; COPD; RISK; METAANALYSIS; POWDER AB Objectives This post hoc analysis of TIOtropium Safety and Performance In Respimat (TIOSPIR) evaluated safety and exacerbation efficacy in patients with stable (2months) use of tiotropium HandiHaler 18 mu g (HH18) prior to study entry, to evaluate whether there was a difference in risk for patients who switched from HH18 to tiotropium Respimat 2.5 mu g (R2.5) or 5 mu g (R5). Setting TIOSPIR (n=17135) was an international, Phase IIIb/IV, randomised, double-blind, parallel-group, event-driven trial. Participants Patients from TIOSPIR with chronic obstructive pulmonary disease (COPD) and postbronchodilator ratio of forced expiratory volume in 1s to forced vital capacity 0.70, receiving HH18 before study entry, were analysed (n=2784). Interventions Patients were randomised to once-daily tiotropium R2.5 (n=914), R5 (n=918) or HH18 (n=952) for 2-3years. Primary and secondary outcome measures Primary outcomes: time to death (safety) and time to first COPD exacerbation (efficacy). Secondary outcomes: number of exacerbations and time to first major adverse cardiovascular event (MACE). Results Baseline characteristics were similar in all groups. Respimat had a similar mortality risk versus HH18 (vital status follow-up, HR; 95% CI R2.5: 0.87; 0.64 to 1.17; R5: 0.79; 0.58 to 1.07) with no significant differences in the risk and rates of exacerbations and severe exacerbations across treatment groups. Risk of MACE and fatal MACE was similar for Respimat versus HH18 (HR; 95% CI MACE R2.5: 0.73; 0.47 to 1.15; R5: 0.69; 0.44 to 1.08; fatal MACE R2.5: 0.57; 0.27 to 1.19; R5: 0.67; 0.33 to 1.34). Overall risk of a fatal event (on treatment) was lower for R5 versus HH18 (HR; 95% CI R2.5: 0.78; 0.55 to 1.09; R5: 0.62; 0.43 to 0.89). Conclusions This analysis indicates that it is safe to switch patients from tiotropium HandiHaler to tiotropium Respimat, and that the efficacy is maintained over the switch. Trial registration number NCT01126437; Post-results. C1 [Dahl, Ronald] Odense Univ Hosp, Allergy Ctr, DK-5000 Odense C, Denmark. [Calverley, Peter M. A.] Aintree Univ Hosp NHS Fdn Trust, Clin Sci Ctr, Inst Ageing & Chron Dis, Liverpool L9 7AL, Merseyside, England. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, Pulm Crit Care Dept, San Antonio, TX 78229 USA. [Anzueto, Antonio] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Metzdorf, Norbert] Boehringer Ingelheim Pharma GmbH & Co KG, TA Resp Dis, Ingelheim, Germany. [Fowler, Andy] Boehringer Ingelheim Pharma Ltd, Clin Res, Bracknell, Berks, England. [Mueller, Achim] Boehringer Ingelheim Pharma GmbH & Co KG, Biometr & Data Management, Biberach, Germany. [Wise, Robert] Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD USA. [Dusser, Daniel] Univ Paris 05, Hop Cochin, Dept Pneumol, AP HP, Paris, France. RP Dahl, R (reprint author), Odense Univ Hosp, Allergy Ctr, DK-5000 Odense C, Denmark. EM Ronald.dahl2@rsyd.dk FU Boehringer Ingelheim FX The TIOSPIR trial was funded by Boehringer Ingelheim. The funding source participated in the design and conduct of the study, the analysis or interpretation of the data and the preparation of the manuscript before publication. NR 26 TC 4 Z9 4 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 2015 VL 5 IS 12 AR e009015 DI 10.1136/bmjopen-2015-009015 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA DB9MB UT WOS:000368839100068 PM 26715479 ER PT J AU Gradus, JL Farkas, DK Svensson, E Ehrenstein, V Lash, TL Milstein, A Adler, N Sorensen, HT AF Gradus, Jaimie L. Farkas, Dora Kormendine Svensson, Elisabeth Ehrenstein, Vera Lash, Timothy L. Milstein, Arnold Adler, Nancy Sorensen, Henrik Toft TI Associations between stress disorders and cardiovascular disease events in the Danish population SO BMJ OPEN LA English DT Article DE MENTAL HEALTH; CARDIOLOGY; EPIDEMIOLOGY ID CORONARY-HEART-DISEASE; MYOCARDIAL-INFARCTION; RISK; EPIDEMIOLOGY; SYMPTOMS; VETERANS; REGISTER; STROKE; MORTALITY; DIAGNOSES AB Objectives Post-traumatic stress disorder (PTSD) is a well-documented risk factor for cardiovascular disease (CVD). However, it is unknown whether another common stress disorderadjustment disorderis also associated with an increased risk of CVD and whether gender modifies these associations. The aim of this study was to examine the overall and gender-stratified associations between PTSD and adjustment disorder and 4 CVD events. Design Prospective cohort study utilising Danish national registry data. Setting The general population of Denmark. Participants PTSD (n=4724) and adjustment disorder (n=64855) cohorts compared with the general population of Denmark from 1995 to 2011. Primary outcome measures CVD events including myocardial infarction (MI), stroke, ischaemic stroke and venous thromboembolism (VTE). Standardised incidence rates and 95% CIs were calculated. Results Associations were found between PTSD and all 4 CVD events ranging from 1.5 (95% CI 1.1 to 1.9) for MI to 2.1 (95% CI 1.7 to 2.7) for VTE. Associations that were similar in magnitude were also found for adjustment disorder and all 4 CVD events: 1.5 (95% CI 1.4 to 1.6) for MI to 1.9 (95% CI 1.8 to 2.0) for VTE. No gender differences were noted. Conclusions By expanding beyond PTSD and examining a second stress disorderadjustment disorderthis study provides evidence that stress-related psychopathology is associated with CVD events. Further, limited evidence of gender differences in associations for either of the stress disorders and CVD was found. C1 [Gradus, Jaimie L.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Farkas, Dora Kormendine] Boston Univ, Dept Psychiat & Epidemiol, Boston, MA 02215 USA. [Gradus, Jaimie L.; Farkas, Dora Kormendine; Svensson, Elisabeth; Ehrenstein, Vera; Lash, Timothy L.; Sorensen, Henrik Toft] Aarhus Univ Hosp, Dept Clin Epidemiol, Aarhus, Denmark. [Lash, Timothy L.] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA USA. [Milstein, Arnold] Stanford Univ, Clin Excellence Res Ctr, Stanford, CA 94305 USA. [Adler, Nancy] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Gradus, JL (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. EM Jaimie.gradus@va.gov FU Program for Clinical Research Infrastructure (PROCRIN); National Institute of Mental Health [1R21MH094551-01A1] FX This work was supported by the Program for Clinical Research Infrastructure (PROCRIN) established by the Lundbeck Foundation and the Novo Nordisk Foundation, and the Aarhus University Research Foundation, and by a National Institute of Mental Health grant: 'Constructing a Danish Reaction to Severe Stress Cohort' (1R21MH094551-01A1), JLG, Principal Investigator. NR 45 TC 3 Z9 3 U1 3 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 2015 VL 5 IS 12 AR e009334 DI 10.1136/bmjopen-2015-009334 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA DB9MB UT WOS:000368839100091 PM 26667014 ER PT J AU Gutnik, L Dieleman, J Dare, AJ Shrime, MG Yamey, G AF Gutnik, L. Dieleman, J. Dare, A. J. Shrime, Mark G. Yamey, Gavin TI Funding allocation to surgery in low and middle-income countries: a retrospective analysis of contributions from the USA (vol 5, e008780, 2015) SO BMJ OPEN LA English DT Correction C1 [Shrime, Mark G.] Massachusetts Eye & Ear Infirm, Off Global Surg, Boston, MA 02114 USA. [Shrime, Mark G.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Yamey, Gavin] Duke Univ, Duke Global Hlth Inst, Durham, NC USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2015 VL 5 IS 11 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA DB9MK UT WOS:000368840100055 ER PT J AU Miller, JE Korn, D Ross, JS AF Miller, Jennifer E. Korn, David Ross, Joseph S. TI Clinical trial registration, reporting, publication and FDAAA compliance: a cross-sectional analysis and ranking of new drugs approved by the FDA in 2012 SO BMJ OPEN LA English DT Article ID CLINICALTRIALS.GOV; ACCREDITATION; PHARMA AB Objective: To evaluate clinical trial registration, reporting and publication rates for new drugs by: (1) legal requirements and (2) the ethical standard that all human subjects research should be publicly accessible to contribute to generalisable knowledge. Design: Cross-sectional analysis of all clinical trials submitted to the Food and Drug Administration (FDA) for drugs approved in 2012, sponsored by large biopharmaceutical companies. Data sources: Information from Drugs@FDA, ClinicalTrials.gov, MEDLINE-indexed journals and drug company communications. Main outcome measures: Clinical trial registration and results reporting in ClinicalTrials.gov, publication in the medical literature, and compliance with the 2007 FDA Amendments Acts (FDAAA), analysed on the drug level. Results: The FDA approved 15 drugs sponsored by 10 large companies in 2012. We identified 318 relevant trials involving 99 599 research participants. Per drug, a median of 57% (IQR 32-83%) of trials were registered, 20% (IQR 12-28%) reported results in ClinicalTrials.gov, 56% (IQR 41-83%) were published, and 65% (IQR 41-83%) were either published or reported results. Almost half of all reviewed drugs had at least one undisclosed phase II or III trial. Per drug, a median of 17% (IQR 8-20%) of trials supporting FDA approvals were subject to FDAAA mandated public disclosure; of these, a median of 67% (IQR 0-100%) were FDAAA-compliant. 68% of research participants (67 629 of 99 599) participated in FDAAA-subject trials, with 51% (33 405 of 67 629) enrolled in noncompliant trials. Transparency varied widely among companies. Conclusions: Trial disclosures for new drugs remain below legal and ethics standards, with wide variation in practices among drugs and their sponsors. Best practices are emerging. 2 of our 10 reviewed companies disclosed all trials and complied with legal disclosure requirements for their 2012 approved drugs. Ranking new drugs on transparency criteria may improve compliance with legal and ethics standards and the quality of medical knowledge. C1 [Miller, Jennifer E.] NYU, Sch Med, Bioeth Int, Langone Med Ctr, New York, NY USA. [Korn, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Edmond J Safra Ctr Eth, Cambridge, MA 02138 USA. [Ross, Joseph S.] Yale Univ, Sch Med, Dept Internal Med, Gen Internal Med Sect, New Haven, CT 06510 USA. [Ross, Joseph S.] Yale Univ, Sch Med, Dept Internal Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT 06510 USA. [Ross, Joseph S.] Yale Univ, Sch Publ Hlth, Dept Hlth Policy & Management, New Haven, CT USA. [Ross, Joseph S.] Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. RP Miller, JE (reprint author), NYU, Sch Med, Bioeth Int, Langone Med Ctr, New York, NY USA. EM jennifer.miller@nyumc.org OI Miller, Jennifer/0000-0002-3591-369X FU Harvard University's Edmond J. Safra Center for Ethics; Duke University's Kenan Institute for Ethics; Duke University's Trinity College of Arts and Sciences; Duke University'sFuqua School of Business; Fordham University's Global Healthcare Innovation Management Center; Susan G. Komen Foundation; Raskob Foundation; Bioethics International; Harvard Medical School Center for Bioethics; Petrie-Flom Center for Health Law, Biotechnology, and Bioethics at Harvard Law School; Harvard Global Health Institute; Harvard University Program in Ethics and Health; National Institute on Aging [K08 AG032886]; American Federation for Aging Research through the Paul B. Beeson Career Development Award Program; Yale University from Medtronic, Inc FX The conceptualisation and pilot of this study and index (called the Good Pharma Scorecard) were supported by Harvard University's Edmond J. Safra Center for Ethics; Duke University's Kenan Institute for Ethics, Trinity College of Arts and Sciences and Fuqua School of Business; Fordham University's Global Healthcare Innovation Management Center; Susan G. Komen Foundation; Raskob Foundation; and Bioethics International. A conference exploring the rating concept (co-chaired by JEM and Nir Eyal) was held at Harvard Medical School, funded by the Division of Medical Ethics (currently the Harvard Medical School Center for Bioethics); the Petrie-Flom Center for Health Law, Biotechnology, and Bioethics at Harvard Law School; the Harvard Global Health Institute; and the Harvard University Program in Ethics and Health. JSR is supported by the National Institute on Aging (K08 AG032886) and by the American Federation for Aging Research through the Paul B. Beeson Career Development Award Program and receives research support through Yale University from Medtronic, Inc and Johnson & Johnson to develop methods of clinical trial data sharing, from the Centers of Medicare and Medicaid Services (CMS) to develop and maintain performance measures that are used for public reporting, and from the Food and Drug Administration (FDA) to develop methods for postmarket surveillance of medical devices. Bioethics International and the Laura and John Arnold Foundation will support further development and implementation of the ranking system described in this paper. NR 18 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 2015 VL 5 IS 11 AR e009758 DI 10.1136/bmjopen-2015-009758 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA DB9MK UT WOS:000368840100114 PM 26563214 ER PT J AU Petkovic, G Charlesworth, JEG Kelley, J Miller, F Roberts, N Howick, J AF Petkovic, Grace Charlesworth, James E. G. Kelley, John Miller, Franklin Roberts, Nia Howick, Jeremy TI Effects of placebos without deception compared with no treatment: protocol for a systematic review and meta-analysis SO BMJ OPEN LA English DT Review ID CLINICAL-PRACTICE; NONCONSCIOUS ACTIVATION; CONDITIONED PLACEBO; INFORMED CONSENT; POWERFUL PLACEBO; ETHICS; TRIAL; ANALGESIA; POWERLESS; RESPONSES AB Introduction: Placebos have long provided a robust control for evaluating active pharmacological preparations, but frequently demonstrate a variable therapeutic effect when delivered in double-blinded placebo-controlled trials. Delivery of placebos as treatment alone has been considered unethical, as it has been thought that deception is essential for their effect. However, recent evidence suggests that clinical benefit can be derived from placebos delivered without deception (unblinded/open-label) manner. Here, we present a protocol for the first systematic review and meta-analysis of studies of the effects of non-deceptive placebos compared with no treatment. Methods and analysis: This protocol will compare the effect of placebos delivered non-deceptively to no treatment. It will also assess the methods of delivery used for non-deceptive placebos. Studies will be sought through relevant database searches and will include those within disease settings and those among healthy controls. To be included, trials must include both non-deceptive (open-label) placebo and no treatment groups. All data extraction and analysis will be conducted by two independent reviewers. The analysis will evaluate any differences in outcome measures between the non-deceptive placebo and no treatment groups. Outcome measures will be the clinically-relevant outcomes detailed in the primary papers. The delivery methods, such as verbal instructions, which may provide positive expectations and outcomes, of non-deceptive placebos will also be assessed. Each study will be comprehensively assessed for bias. Subgroup analyses will identify any discrepancies among heterogeneous data. Ethics and dissemination: This review does not require ethical approval. The completed review will be widely disseminated by publication and social media where appropriate. This protocol has been registered on PROSPERO (2015: CRD42015023347). C1 [Petkovic, Grace; Charlesworth, James E. G.; Roberts, Nia; Howick, Jeremy] Univ Oxford, Nuffield Dept Primary Care Hlth Sci, Oxford, England. [Kelley, John] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Kelley, John] Endicott Coll, Dept Psychol, Beverly, MA USA. [Miller, Franklin] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Petkovic, G (reprint author), Univ Oxford, Nuffield Dept Primary Care Hlth Sci, Oxford, England. EM grace.petkovic@hmc.ox.ac.uk NR 47 TC 2 Z9 2 U1 1 U2 10 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 2015 VL 5 IS 11 AR e009428 DI 10.1136/bmjopen-2015-009428 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA DB9MK UT WOS:000368840100130 PM 26610763 ER PT J AU Cho, PS Saidi, RF Cutie, CJ Ko, DSC AF Cho, P. S. Saidi, R. F. Cutie, C. J. Ko, D. S. C. TI Competitive Market Analysis of Transplant Centers and Discrepancy of Wait-Listing of Recipients for Kidney Transplantation SO INTERNATIONAL JOURNAL OF ORGAN TRANSPLANTATION MEDICINE LA English DT Article DE Kidney transplantation; Competition; Allocation; Wait-list; Market analysis ID MISMATCHED RENAL-TRANSPLANTATION; UNITED-STATES; CARDIAC DEATH; MAINTENANCE IMMUNOSUPPRESSION; ORGAN DONATION; DONORS; OVERSIGHT AB Background: There are over 250 kidney transplant programs in the USA. Objective: To determine if highly competitive regions, defined as regions with a higher number of transplant centers, will approve and wait-list more end-stage renal disease (ESRD) candidates for transplant despite consistent incidence and prevalence of ESRD nationwide. Methods: ESRD Network and OPTN data completed in 2011 were obtained from all transplant centers including listing data, market saturation, market share, organs transplanted, and ESRD prevalence. Herfindahl-Hirschman Index (HHI) was used to measure the size of firms in relation to the industry to determine the amount of competition. Results: States were separated into 3 groups (HHI<1000 considered competitive; HHI 1000-1800 considered moderate competition; and HHI>1800 considered highly concentrated). The percentage of ESRD patients listed in competitive, moderate, and highly concentrated regions were 19.73%, 17.02%, and 13.75%, respectively. The ESRD listing difference between competitive versus highly concentrated was significant (p<0.05). Conclusion: When there is strong competition without a dominant center as defined by the HHI, the entire state tends to list more patients for transplant to drive up their own center's market share. Our analysis of the available national data suggests a discrepancy in access for ESRD patient to transplantation due to transplant center competition. C1 [Cho, P. S.; Cutie, C. J.; Ko, D. S. C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA USA. [Saidi, R. F.] Brown Univ, Alpert Med Sch, Dept Surg, Div Organ Transplantat, Providence, RI 02903 USA. [Ko, D. S. C.] Harvard Univ, Sch Med, Dept Surg, Div Transplantat,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Saidi, RF (reprint author), Brown Univ, Alpert Med Sch, Dept Surg, Div Organ Transplantat,Surg, 593 Eddy St,APC 921, Providence, RI 02903 USA. EM Reza_Saidi@Brown.edu NR 23 TC 1 Z9 1 U1 0 U2 0 PU AVICENNA ORGAN TRANSPLANT CENTER PI FARS PA PHASE 2, DOKOHAK RD, SADRA TOWN, SHIRAZ, FARS, 71994-67985, IRAN SN 2008-6490 EI 2008-6482 J9 INT J TRANSPLANT MED JI Int. J. Organ Transplant. Med. PY 2015 VL 6 IS 4 BP 141 EP 149 PG 9 WC Transplantation SC Transplantation GA DC2RU UT WOS:000369064800001 PM 26576259 ER PT J AU Liu, SR Schulz, MS Waldinger, RJ AF Liu, Sabrina R. Schulz, Marc S. Waldinger, Robert J. TI Cumulative Contribution of Child Maltreatment to Emotional Experience and Regulatory Intent in Intimate Adult Interactions SO JOURNAL OF AGGRESSION MALTREATMENT & TRAUMA LA English DT Article DE childhood trauma; child maltreatment; couples; emotion processing; emotion regulation; long-term effects; multitype maltreatment; video recall ID POSTTRAUMATIC-STRESS-DISORDER; MAJOR DEPRESSIVE DISORDER; SEXUAL-ABUSE; EMPIRICAL LITERATURE; MARITAL INTERACTION; EMPATHIC ACCURACY; SELF-REPORT; TRAUMA; NEGLECT; COUPLES AB This study examined the link between experiencing multiple types of child maltreatment and intentions to control emotion during charged discussions with intimate partners in adulthood, and whether the link is mediated by intensity of negative emotions. Using video recall, 97 couples rated their levels of emotions and intentions to control emotion during charged discussions with partners. Number of types of child maltreatment reported was linked with effort to control emotion, and the relationship was partially mediated by intensity of participants' feelings of hostility. For men, the link was also partially mediated by self-reported sadness and anxiety. Findings underscore the importance of attending to abuse survivors' experiences of and attempts to manage intense emotions in treatment, particularly in couples therapy. C1 [Liu, Sabrina R.; Waldinger, Robert J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Adult Dev, Boston, MA USA. [Schulz, Marc S.] Bryn Mawr Coll, Dept Psychol, Bryn Mawr, PA 19010 USA. RP Liu, SR (reprint author), Univ Calif Santa Barbara, Dept Counseling Clin & Sch Psychol, Gevirtz Grad Sch Educ, Santa Barbara, CA 93103 USA. EM sliu@education.ucsb.edu FU National Institute of Mental Health [K08 MH1555] FX This study was supported by a grant from the National Institute of Mental Health (K08 MH1555) to Robert J. Waldinger, Principal Investigator. NR 78 TC 0 Z9 0 U1 6 U2 8 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1092-6771 EI 1545-083X J9 J AGGRESS MALTREAT T JI J. Aggress. Maltreatment Trauma PY 2015 VL 24 IS 6 BP 636 EP 655 DI 10.1080/10926771.2015.1049768 PG 20 WC Psychology, Clinical; Criminology & Penology; Family Studies; Psychiatry SC Psychology; Criminology & Penology; Family Studies; Psychiatry GA DB7DI UT WOS:000368674300003 ER PT J AU Warren, T Milburn, E Patson, ND Dickey, MW AF Warren, Tessa Milburn, Evelyn Patson, Nikole D. Dickey, Michael Walsh TI Comprehending the impossible: what role do selectional restriction violations play? SO LANGUAGE COGNITION AND NEUROSCIENCE LA English DT Article DE language comprehension; plausibility; eye tracking; sentence processing; reading ID E-Z READER; EYE-MOVEMENTS; LANGUAGE COMPREHENSION; PLAUSIBILITY; KNOWLEDGE; INTEGRATION; INFORMATION; MEMORY AB To elucidate how different kinds of knowledge are used during comprehension, readers' eye movements were monitored as they read sentences that were: plausible, impossible because of a selectional restriction violation (SRV) or impossible because of a violation of general world knowledge. Eye movements on the pre-critical, critical, and post-critical words evidenced disruption in the SRV condition compared to the other two conditions. These findings suggest that disruption associated with reading about impossible events is not directly determined by how impossible the event seems. Rather, the relationship between the verb and arguments in the sentence seems to matter. These findings are the strongest evidence to date that processing effects associated with selectional restrictions can dissociate from those associated with general world knowledge about events. C1 [Warren, Tessa; Milburn, Evelyn] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. [Warren, Tessa; Milburn, Evelyn] Univ Pittsburgh, Learning Res & Dev Ctr, Pittsburgh, PA 15260 USA. [Patson, Nikole D.] Ohio State Univ, Dept Psychol, Marion, OH USA. [Dickey, Michael Walsh] Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA USA. [Dickey, Michael Walsh] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Warren, T (reprint author), Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. EM tessa@pitt.edu OI Dickey, Michael Walsh/0000-0002-9068-3313 FU National Institutes of Health [R01DC011520] FX This research was supported by the National Institutes of Health [grant number R01DC011520] to the first and fourth authors. It is the result of work supported with resources and the use of facilities at the VA Pittsburgh Healthcare System. NR 36 TC 2 Z9 2 U1 1 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 2327-3798 EI 2327-3801 J9 LANG COGN NEUROSCI JI Lang. Cogn. Neurosci. PY 2015 VL 30 IS 8 BP 932 EP 939 DI 10.1080/23273798.2015.1047458 PG 8 WC Audiology & Speech-Language Pathology; Behavioral Sciences; Linguistics; Psychology, Experimental SC Audiology & Speech-Language Pathology; Behavioral Sciences; Linguistics; Psychology GA DC2PZ UT WOS:000369060000008 PM 26618186 ER PT B AU Ott, PA Hodi, FS AF Ott, Patrick A. Hodi, F. Stephen BE Ascierto, PA Stroncek, DF Wang, E TI T Cell Modulation: Anti-PD-1 Antibodies for the Treatment of Cancer SO DEVELOPMENTS IN T CELL BASED CANCER IMMUNOTHERAPIES SE Cancer Drug Discovery and Development LA English DT Article; Book Chapter DE T cell; PD-1; PD-L1; CTLA-4; Immune checkpoint blockade; Cancer ID PROGRAMMED DEATH-1 PD-1; HUMAN OVARIAN-CANCER; B7-H1 PD-L1; DILATED CARDIOMYOPATHY; CLINICAL-SIGNIFICANCE; ANTITUMOR IMMUNITY; B7 FAMILY; NOD MICE; EXPRESSION; PATHWAY AB The expression of inhibitory receptors on tumor specific T cells leads to compromised effector function such as decreased proliferation, cytokine secretion, and tumor cell lysis. These receptors can be targeted therapeutically using monoclonal antibodies, an approach that was termed "checkpoint blockade". The improved survival of advanced melanoma patients treated with the anti-CTLA-4 antibody ipilimumab validates this new treatment concept. Inhibition of another inhibitory pathway, PD-1/PD-L1, using monoclonal antibodies has recently shown much promise in the treatment of melanoma, renal cell cancer, non-small cell lung cancer, among other tumor types. Durable anti-tumor activity with a favorable safety profile has lead to fast paced clinical development of many compounds targeting both PD-1 and PD-L1. C1 [Ott, Patrick A.; Hodi, F. Stephen] Harvard Univ, Sch Med, Melanoma Dis Ctr, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. [Ott, Patrick A.; Hodi, F. Stephen] Ctr Immunooncol, Boston, MA 02215 USA. RP Ott, PA (reprint author), Harvard Univ, Sch Med, Melanoma Dis Ctr, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM Patrick_Ott@DFCI.harvard.edu NR 60 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-3-319-21167-1; 978-3-319-21166-4 J9 CANCER DRUG DISCOV D JI Canc. Drug. Disc. Dev. PY 2015 BP 231 EP 244 DI 10.1007/978-3-319-21167-1_10 D2 10.1007/978-3-319-21167-1 PG 14 WC Oncology; Immunology SC Oncology; Immunology GA BE1UP UT WOS:000368600900011 ER PT S AU Chaudhuri, AR Wei, R Bhattacharya, A Hamilton, R AF Chaudhuri, Asish R. Wei, Rochelle Bhattacharya, Arunabh Hamilton, Ryan BE Shaw, AC TI Fluorescence-Based Approaches for Quantitative Assessment of Protein Carbonylation, Protein Disulfides, and Protein Conformation in Biological Tissues SO IMMUNOSENESCENCE: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Protein oxidation; Carbonylation; Disulfide; Oxidative stress ID METAL-CATALYZED OXIDATION; SKELETAL-MUSCLE; STRESS; STATE AB Protein oxidation and misfolding have been considered as key players for progression of aging and etiology of various pathological conditions. However, few attempts have been made to develop sensitive and reproducible assays to quantify the changes in protein oxidation and alteration in structure. Here we describe three distinct fluorescence-based assays to quantify changes in protein oxidation, namely carbonylation and disulfides and alteration in protein surface hydrophobicity as a reporter for protein conformation. These techniques will provide investigators the opportunity to address important biological questions in their experimental models. C1 [Chaudhuri, Asish R.] UT Southwestern Med Ctr, Dallas, TX USA. [Chaudhuri, Asish R.; Wei, Rochelle; Bhattacharya, Arunabh; Hamilton, Ryan] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Chaudhuri, Asish R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Chaudhuri, Asish R.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Bhattacharya, Arunabh; Hamilton, Ryan] Univ Texas Hlth Sci Ctr San Antonio, Cellular & Struct Biol, San Antonio, TX 78229 USA. RP Chaudhuri, AR (reprint author), UT Southwestern Med Ctr, Dallas, TX USA. NR 23 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-2963-4; 978-1-4939-2962-7 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1343 BP 155 EP 173 DI 10.1007/978-1-4939-2963-4_13 D2 10.1007/978-1-4939-2963-4 PG 19 WC Immunology SC Immunology GA BE1RY UT WOS:000368438800014 PM 26420716 ER PT J AU Bentefour, EH Both, S Tang, SK Lu, HM AF Bentefour, El Hassane Both, Stefan Tang, Shikui Lu, Hsiao-Ming TI Using CBCT for pretreatment range check in proton therapy: a phantom study for prostate treatment by anterior-posterior beam SO JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS LA English DT Article DE CBCT; WEPL calculation; range uncertainty; proton therapy ID VERIFICATION AB This study explores the potential of cone-beam computed tomography (CBCT) for monitoring relative beam range variations due to daily changes in patient anatomy for prostate treatment by anterior proton beams. CBCT was used to image an anthropomorphic pelvic phantom, in eight sessions on eight different days. In each session, the phantom was scanned twice, first at a standard position as determined by the room lasers, and then after it was shifted by 10 mm translation randomly along one of the X, Y, or Z directions. The filling of the phantom bladder with water was not refreshed from day to day, inducing gradual change of the water-equivalent path length (WEPL) across the bladder. MIMvista (MIM) software was used to perform image registration and re-alignment of all the scans with the scan from the first session. The XiO treatment planning system was used to perform data analysis. It was found that, although the Hounsfield unit numbers in CBCT have substantially larger fluctuations than those in diagnostic CT, CBCT datasets taken for daily patient positioning could potentially be used to monitor changes in patient anatomy. The reproducibility of the WEPL, computed using CBCT along anterior-posterior (AP) paths across and around the phantom prostate, over a volume of 360 cc, is sufficient for detecting daily WEPL variations that are equal to or larger than 3 mm. This result also applies to CBCT scans of the phantom after it is randomly shifted from the treatment position by 10 mm. limiting the interest to WEPL variation over a specific path within the same CBCT slice, one can detect WEPL variation smaller than 1 mm. That is the case when using CBCT for tracking daily change of the WEPL across the phantom bladder that was induced by spontaneous change in the bladder filling due to evaporation. In summary, the phantom study suggests that CBCT can be used for monitoring day to day WEPL variations in a patient. The method can detect WEPL variation equal to or greater than 3 mm. The study calls for further investigation using the CBCT data from real patients. If confirmed with real patients' data, CBCT could become, in addition to patient setup, a standard tool for proton therapy pretreatment beam range check. C1 [Bentefour, El Hassane] Ion Beam Applicat Sa, Adv Technol Grp, Louvain La Neuve, Belgium. [Both, Stefan] Univ Penn, Philadelphia, PA 19104 USA. [Tang, Shikui; Lu, Hsiao-Ming] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Bentefour, EH (reprint author), Ion Beam Applicat IBA, Adv Technol Grp ATG, 3 Chemin Cyclotron, B-1348 Louvain La Neuve, Belgium. EM Hassan.Bentefour@iba-group.com NR 20 TC 0 Z9 0 U1 0 U2 1 PU MULTIMED INC PI TORONTO PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA SN 1526-9914 J9 J APPL CLIN MED PHYS JI J. Appl. Clin. Med. Phys PY 2015 VL 16 IS 6 BP 472 EP 483 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DB2LV UT WOS:000368341100044 PM 28297527 ER PT J AU Kalra, A Forman, DE Goodlin, SJ AF Kalra, Ankur Forman, Daniel E. Goodlin, Sarah J. TI Medical decision making for older adults: an international perspective comparing the United States and India SO JOURNAL OF GERIATRIC CARDIOLOGY LA English DT Article DE Advance care planning; Advance directive; End-of-life; India; Surrogate decision-making ID ADVANCE DIRECTIVES; HEALTH-CARE; LIFE; SURROGATES; EVOLUTION; FUTILITY; END; LAW AB There has been a significant decline in cardiovascular morbidity and mortality amidst pervasive advances in care, including percutaneous revascularization, mechanical circulatory support, and transcatheter valvular therapies. While advancing therapies may add significant longevity, they also bring about new end-of-life decision-making challenges for patients and their families who also must weigh the advantages of reduced mortality to the possibility of longer lives consisting of high morbidity, frailty, pain, and poor quality of living. Advance care entails options of withholding or withdrawing therapies, and has become a familiar part of cardiovascular care for older patients in Western countries. However, as advanced cardiovascular practices extend to developing countries, the interrelated concept of advance care is rarely straight forward as it is affected by local cultural traditions and mores, and can lead to very different inferences and use. This paper discusses the concepts of advance care planning, surrogate decision-making, orders for resuscitation and futility in patients with cardiac disease with comparisons of West to East, focusing particularly on the United States versus India. C1 [Goodlin, Sarah J.] Oregon Hlth & Sci Univ, Dept Geriatr Med, Portland, OR 97201 USA. [Kalra, Ankur] Beth Israel Deaconess Med Ctr, Div Intervent Cardiol, Boston, MA 02215 USA. [Kalra, Ankur] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kalra, Ankur] Kalra Hosp SRCNC Pvt Ltd, Dept Med, Div Cardiol, New Delhi, India. [Forman, Daniel E.] Univ Pittsburgh, Med Ctr, Sect Geriatr Cardiol, Pittsburgh, PA USA. [Forman, Daniel E.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Goodlin, Sarah J.] Vet Affairs Portland Hlth Care Syst, Portland, OR USA. RP Goodlin, SJ (reprint author), Oregon Hlth & Sci Univ, Dept Geriatr Med, Portland, OR 97201 USA. EM sarah.goodlin@va.gov NR 32 TC 0 Z9 0 U1 1 U2 2 PU SCIENCE PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 1671-5411 J9 J GERIATR CARDIOL JI J. Geriatr. Cardiol. PY 2015 VL 12 IS 4 BP 329 EP 334 PG 6 WC Cardiac & Cardiovascular Systems; Geriatrics & Gerontology SC Cardiovascular System & Cardiology; Geriatrics & Gerontology GA DB3MR UT WOS:000368416200001 PM 26346983 ER PT S AU Ullal, AV Weissleder, R AF Ullal, Adeeti V. Weissleder, Ralph BE Singh, AK Chandrasekaran, A TI Photocleavable DNA Barcoding Antibodies for Multiplexed Protein Analysis in Single Cells SO SINGLE CELL PROTEIN ANALYSIS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Multiplexing; Proteomics; Single cell analysis; Pathway analysis; Fine needle aspirates; DNA barcoding; Antibody conjugation AB We describe a DNA-barcoded antibody sensing technique for single cell protein analysis in which the barcodes are photocleaved and digitally detected without amplification steps (Ullal et al., Sci Transl Med 6:219, 2014). After photocleaving the unique similar to 70mer DNA barcodes we use a fluorescent hybridization technology for detection, similar to what is commonly done for nucleic acid readouts. This protocol offers a simple method for multiplexed protein detection using 100+ antibodies and can be performed on clinical samples as well as single cells. C1 [Ullal, Adeeti V.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. RP Ullal, AV (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. NR 10 TC 1 Z9 1 U1 1 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-2987-0; 978-1-4939-2986-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1346 BP 47 EP 54 DI 10.1007/978-1-4939-2987-0_4 D2 10.1007/978-1-4939-2987-0 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BE1TP UT WOS:000368527000005 PM 26542714 ER PT J AU Gamarra, JM Luciano, MT Gradus, JL Stirman, SW AF Gamarra, Jennifer M. Luciano, Matthew T. Gradus, Jaimie L. Stirman, Shannon Wiltsey TI Assessing Variability and Implementation Fidelity of Suicide Prevention Safety Planning in a Regional VA Healthcare System SO CRISIS-THE JOURNAL OF CRISIS INTERVENTION AND SUICIDE PREVENTION LA English DT Article DE safety plan; suicide; veterans; fidelity ID COGNITIVE THERAPY; CONTRACT; DEPRESSION AB Background: In 2008, the Veterans Health Administration (VHA) implemented the use of safety planning for suicide prevention. A safety plan is a list of strategies, developed collaboratively with a provider, for a patient to use when suicide risk is elevated. Despite the use of safety plans in VHA, little is known about implementation fidelity, the extent to which safety plans are delivered as intended, or patient-level outcomes of safety planning. Aims: This study aimed to explore the implementation fidelity of safety planning in a regional VHA hospital and examine the associations between safety plan quality and completeness with patient outcomes. Method: A comprehensive chart review was conducted for patients who were flagged as high risk for suicide (N = 200). Completeness and quality were coded, as well as information about patient and provider interactions regarding safety plan use. Results: Safety plans were mostly complete and of moderate quality, although variability existed, particularly in quality. Limited evidence of follow-up regarding safety planning was found in the medical charts. Higher quality was associated with fewer subsequent psychiatric hospitalizations. Conclusion: Variability in implementation fidelity and infrequent follow-up suggest a need for additional training and support regarding the use of safety plans for suicide prevention. C1 [Gamarra, Jennifer M.; Luciano, Matthew T.; Gradus, Jaimie L.; Stirman, Shannon Wiltsey] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Gamarra, Jennifer M.; Gradus, Jaimie L.; Stirman, Shannon Wiltsey] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Gradus, Jaimie L.] Boston Univ, Sch Publ Hlth, Dept Psychiat & Epidemiol, Boston, MA USA. [Luciano, Matthew T.] Univ Memphis, Dept Psychol, Memphis, TN 38152 USA. [Gamarra, Jennifer M.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Stirman, Shannon Wiltsey] VA Palo Alto Healthcare Syst, Natl Ctr PTSD, Palo Alto, CA USA. RP Gamarra, JM (reprint author), Univ Calif Los Angeles, Dept Psychol, 1177 Franz Hall, Los Angeles, CA 90034 USA. FU NIMH NIH HHS [R25 MH080916, R00 MH-080100, R00 MH080100, R21 MH099169] NR 14 TC 0 Z9 0 U1 1 U2 2 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 0227-5910 EI 2151-2396 J9 CRISIS JI Crisis PY 2015 VL 36 IS 6 BP 433 EP 439 DI 10.1027/0227-5910/a000345 PG 7 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA DA8IB UT WOS:000368047200007 PM 26648231 ER PT S AU Kwong, KK AF Kwong, Kenneth K. BE Uludag, K Ugurbil, K Berliner, L TI The Road to fMRI Using Endogenous MR Blood Contrast SO FMRI: FROM NUCLEAR SPINS TO BRAIN FUNCTIONS SE Biological Magnetic Resonance LA English DT Article; Book Chapter ID MAGNETIC-SUSCEPTIBILITY; SENSORY STIMULATION; BRAIN; PERFUSION; OXYGENATION; FLOW; ACTIVATION; CORTEX; FIELDS; IMAGE C1 [Kwong, Kenneth K.] Massachusetts Gen Hosp, Dept Radiol, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. RP Kwong, KK (reprint author), Massachusetts Gen Hosp, Dept Radiol, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. EM kwong@nmr.mgh.harvard.edu NR 22 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0192-6020 BN 978-1-4899-7591-1; 978-1-4899-7590-4 J9 BIOL MAGN RESON JI Biol. Magn. Reson. PY 2015 VL 30 BP 19 EP 23 DI 10.1007/978-1-4899-7591-1_3 D2 10.1007/978-1-4899-7591-1 PG 5 WC Chemistry, Organic SC Chemistry GA BE1LG UT WOS:000368102000004 ER PT S AU Liu, TT Glover, GH Mueller, BA Greve, DN Rasmussen, J Voyvodic, JT Turner, JA Erp, TGM Mathalon, DH Andersen, K Lu, K Brown, GG Keator, DB Calhoun, VD Lee, HJ Ford, JM Diaz, M O'Leary, DS Gadde, S Preda, A Lim, KO Wible, CG Stern, HS Belger, A McCarthy, G Ozyurt, B Potkin, SG AF Liu, Thomas T. Glover, Gary H. Mueller, Bryon A. Greve, Douglas N. Rasmussen, Jerod Voyvodic, James T. Turner, Jessica A. Erp, Theo G. M. Mathalon, Daniel H. Andersen, Kasper Lu, Kun Brown, Gregory G. Keator, David B. Calhoun, Vince D. Lee, Hyo Jong Ford, Judith M. Diaz, Michele O'Leary, Daniel S. Gadde, Syam Preda, Adrian Lim, Kelvin O. Wible, Cynthia G. Stern, Hal S. Belger, Aysenil McCarthy, Gregory Ozyurt, Burak Potkin, Steven G. CA FBIRN BE Uludag, K Ugurbil, K Berliner, L TI Quality Assurance in Functional MRI SO FMRI: FROM NUCLEAR SPINS TO BRAIN FUNCTIONS SE Biological Magnetic Resonance LA English DT Article; Book Chapter ID INFORMATICS RESEARCH NETWORK; INDEPENDENT COMPONENT ANALYSIS; WORKING-MEMORY TASK; MULTICENTER FMRI; AUDITORY HALLUCINATIONS; NOISE CORRECTION; SCHIZOPHRENIA; BOLD; FBIRN; REPRODUCIBILITY C1 [Liu, Thomas T.; Lu, Kun] Univ Calif San Diego, Ctr Funct MRI, La Jolla, CA 92093 USA. [Liu, Thomas T.; Lu, Kun] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. [Glover, Gary H.] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA. [Mueller, Bryon A.; Lim, Kelvin O.] Univ Minnesota, Minneapolis VA Healthcare Syst, Ctr Magnet Resonance Res, Minneapolis, MN 55454 USA. [Mueller, Bryon A.; Lim, Kelvin O.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55454 USA. [Greve, Douglas N.] Massachusetts Gen Hosp, Martinos Ctr, Boston, MA 02115 USA. [Greve, Douglas N.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. [Rasmussen, Jerod; Erp, Theo G. M.; Keator, David B.; Preda, Adrian; Potkin, Steven G.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92617 USA. [Voyvodic, James T.; Diaz, Michele; Gadde, Syam] Duke Univ, Med Ctr, Brain Imaging & Anal Ctr, Durham, NC USA. [Turner, Jessica A.; Calhoun, Vince D.] Mind Res Network, Albuquerque, NM 87106 USA. [Mathalon, Daniel H.; Ford, Judith M.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Mathalon, Daniel H.; Ford, Judith M.] Univ Calif San Francisco, San Francisco & San Francisco VA Med Ctr, EEG Lab, San Francisco, CA 94143 USA. [Brown, Gregory G.] Univ Calif San Diego, VA San Diego Healthcare Syst, La Jolla, CA 92093 USA. [Brown, Gregory G.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Calhoun, Vince D.] Univ New Mexico, Dept ECE, Albuquerque, NM 87131 USA. [Lee, Hyo Jong] Chonbuk Natl Univ, Dept Comp Sci & Engn, Jeonju Si, South Korea. [O'Leary, Daniel S.] Univ Iowa, Dept Psychiat, Iowa City, IA 52240 USA. [Wible, Cynthia G.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Wible, Cynthia G.] Brockton VAMC, Boston, MA 02115 USA. [Stern, Hal S.] Univ Calif Irvine, Dept Stat, Irvine, CA USA. [Belger, Aysenil] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Belger, Aysenil] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA. [McCarthy, Gregory] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Ozyurt, Burak] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Turner, Jessica A.] Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA. [Andersen, Kasper] Copenhagen Univ Hosp, Ctr Funct & Diagnost Imaging & Res, Danish Res Ctr Magnet Resonance, Hvidovre, Denmark. [FBIRN] Funct Biomed Informat Res Network, Irvine, CA USA. RP Liu, TT (reprint author), Univ Calif San Diego, Ctr Funct MRI, 9500 Gilman Dr,MC 0677, La Jolla, CA 92093 USA. EM ttliu@ucsd.edu NR 47 TC 1 Z9 1 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0192-6020 BN 978-1-4899-7591-1; 978-1-4899-7590-4 J9 BIOL MAGN RESON JI Biol. Magn. Reson. PY 2015 VL 30 BP 245 EP 270 DI 10.1007/978-1-4899-7591-1_10 D2 10.1007/978-1-4899-7591-1 PG 26 WC Chemistry, Organic SC Chemistry GA BE1LG UT WOS:000368102000011 ER PT S AU Wald, LL Triantafyllou, C Hoge, RD AF Wald, Lawrence L. Triantafyllou, Christina Hoge, Richard D. BE Uludag, K Ugurbil, K Berliner, L TI Field Strength Dependence of Contrast and Noise in fMRI SO FMRI: FROM NUCLEAR SPINS TO BRAIN FUNCTIONS SE Biological Magnetic Resonance LA English DT Article; Book Chapter ID INDUCED SIGNAL CHANGES; 7 T; PHYSIOLOGICAL NOISE; SPIN-ECHO; BOLD SIGNAL; VISUAL-CORTEX; PARALLEL MRI; HUMAN BRAIN; IN-VIVO; FLUCTUATIONS C1 [Wald, Lawrence L.; Triantafyllou, Christina] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Wald, Lawrence L.; Triantafyllou, Christina] Harvard Univ, Sch Med, Boston, MA USA. [Hoge, Richard D.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. [Triantafyllou, Christina] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. [Hoge, Richard D.] Inst Univ Geriatrie Montreal, Grp Rech Syst Nerveux Cent, Ctr Rech, Unite Neuroimagerie Fonct, Montreal, PQ, Canada. [Hoge, Richard D.] Univ Montreal, Dept Physiol, Inst Genie Biomed, Montreal, PQ H3C 3J7, Canada. RP Wald, LL (reprint author), Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM wald@nmr.mgh.harvard.edu RI Wald, Lawrence/D-4151-2009 NR 52 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0192-6020 BN 978-1-4899-7591-1; 978-1-4899-7590-4 J9 BIOL MAGN RESON JI Biol. Magn. Reson. PY 2015 VL 30 BP 793 EP 818 DI 10.1007/978-1-4899-7591-1_27 D2 10.1007/978-1-4899-7591-1 PG 26 WC Chemistry, Organic SC Chemistry GA BE1LG UT WOS:000368102000028 ER PT J AU Gueorguiev, G Cotter, C Turcotte, JC Crawford, B Sharp, G Mah'D, M AF Gueorguiev, Gueorgui Cotter, Christopher Turcotte, Julie Catherine Crawford, Bruce Sharp, Gregory Mah'D, Mufeed TI Clinical implementation and error sensitivity of a 3D quality assurance protocol for prostate and thoracic IMRT SO JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS LA English DT Article DE 3D quality assurance; IMRT; COMPASS ID PATIENT-SPECIFIC QA; VERIFICATION SYSTEM; DOSE VERIFICATION; RADIOTHERAPY; DOSIMETRY AB This work aims at three goals: first, to define a set of statistical parameters and plan structures for a 3D pretreatment thoracic and prostate intensity-modulated radiation therapy (IMRT) quality assurance (QA) protocol; secondly, to test if the 3D QA protocol is able to detect certain clinical errors; and third, to compare the 3D QA method with QA performed with single ion chamber and 2D gamma test in detecting those errors. The 3D QA protocol measurements were performed on 13 prostate and 25 thoracic IMRT patients using IBA's COMPASS system. For each treatment planning structure included in the protocol, the following statistical parameters were evaluated: average absolute dose difference (AADD), percent structure volume with absolute dose difference greater than 6% (ADD6), and 3D gamma test. To test the 3D QA protocol error sensitivity, two prostate and two thoracic step-and-shoot IMRT patients were investigated. Errors introduced to each of the treatment plans included energy switched from 6 MV to 10 MV, multileaf collimator (MLC) leaf errors, linac jaws errors, monitor unit (MU) errors, MLC and gantry angle errors, and detector shift errors. QA was performed on each plan using a single ion chamber and 2D array of ion chambers for 2D and 3D QA. Based on the measurements performed, we established a uniform set of tolerance levels to determine if QA passes for each IMRT treatment plan structure: maximum allowed AADD is 6%; maximum 4% of any structure volume can be with ADD6 greater than 6%, and maximum 4% of any structure volume may fail 3D gamma test with test parameters 3%/3 mm DTA. Out of the three QA methods tested the single ion chamber performed the worst by detecting 4 out of 18 introduced errors, 2D QA detected 11 out of 18 errors, and 3D QA detected 14 out of 18 errors. C1 [Gueorguiev, Gueorgui; Mah'D, Mufeed] Univ Massachusetts Lowel, Biomed Engn & Biotechnol Program, Lowell, MA USA. [Gueorguiev, Gueorgui; Cotter, Christopher; Turcotte, Julie Catherine; Crawford, Bruce; Sharp, Gregory] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Gueorguiev, G (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 45 Fruit St, Boston, MA 02114 USA. FU IBA FX Contributing author Mr. Bruce Crawford acknowledges travel support from IBA. Gueorgui Gueorguiev acknowledges receiving funding from IBA for work unrelated to this manuscript project. NR 20 TC 0 Z9 0 U1 2 U2 2 PU MULTIMED INC PI TORONTO PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA SN 1526-9914 J9 J APPL CLIN MED PHYS JI J. Appl. Clin. Med. Phys PY 2015 VL 16 IS 5 BP 179 EP 192 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DB2LT UT WOS:000368340900016 PM 28296111 ER PT J AU Lener, T Gimona, M Aigner, L Borger, V Buzas, E Camussi, G Chaput, N Chatterjee, D Court, FA del Portillo, HA O'Driscoll, L Fais, S Falcon-Perez, JM Felderhoff-Mueser, U Fraile, L Gho, YS Gorgens, A Gupta, RC Hendrix, A Hermann, DM Hill, AF Hochberg, F Horn, PA de Kleijn, D Kordelas, L Kramer, BW Kramer-Albers, EM Laner-Plamberger, S Laitinen, S Leonardi, T Lorenowicz, MJ Lim, SK Lotvall, J Maguire, CA Marcilla, A Nazarenko, I Ochiya, T Patel, T Pedersen, S Pocsfalvi, G Pluchino, S Quesenberry, P Reischl, IG Rivera, FJ Sanzenbacher, R Schallmoser, K Slaper-Cortenbach, I Strunk, D Tonn, T Vader, P van Balkom, BWM Wauben, M El Andaloussi, S Thery, C Rohde, E Giebel, B AF Lener, Thomas Gimona, Mario Aigner, Ludwig Boerger, Verena Buzas, Edit Camussi, Giovanni Chaput, Nathalie Chatterjee, Devasis Court, Felipe A. del Portillo, Hernando A. O'Driscoll, Lorraine Fais, Stefano Falcon-Perez, Juan M. Felderhoff-Mueser, Ursula Fraile, Lorenzo Gho, Yong Song Goergens, Andre Gupta, Ramesh C. Hendrix, An Hermann, Dirk M. Hill, Andrew F. Hochberg, Fred Horn, Peter A. de Kleijn, Dominique Kordelas, Lambros Kramer, Boris W. Kraemer-Albers, Eva-Maria Laner-Plamberger, Sandra Laitinen, Saara Leonardi, Tommaso Lorenowicz, Magdalena J. Lim, Sai Kiang Lotvall, Jan Maguire, Casey A. Marcilla, Antonio Nazarenko, Irina Ochiya, Takahiro Patel, Tushar Pedersen, Shona Pocsfalvi, Gabriella Pluchino, Stefano Quesenberry, Peter Reischl, Ilona G. Rivera, Francisco J. Sanzenbacher, Ralf Schallmoser, Katharina Slaper-Cortenbach, Ineke Strunk, Dirk Tonn, Torsten Vader, Pieter van Balkom, Bas W. M. Wauben, Marca El Andaloussi, Samir Thery, Clotilde Rohde, Eva Giebel, Bernd TI Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper SO JOURNAL OF EXTRACELLULAR VESICLES LA English DT Article DE immunology; neurobiology; haematology; stem cells; tissue regeneration; tumour vaccination; regulation ID MESENCHYMAL STEM-CELLS; ENDOTHELIAL PROGENITOR CELLS; OUTER-MEMBRANE VESICLES; REGULATORY T-CELLS; VERSUS-HOST-DISEASE; TUMOR-DERIVED EXOSOMES; UMBILICAL-CORD BLOOD; NANOPARTICLE TRACKING ANALYSIS; ISCHEMIA-REPERFUSION INJURY; FIELD-FLOW FRACTIONATION AB Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addressed. C1 [Lener, Thomas; Gimona, Mario; Aigner, Ludwig; Laner-Plamberger, Sandra; Schallmoser, Katharina; Rohde, Eva] Paracelsus Med Univ, Spinal Cord Injury & Tissue Regenerat Ctr Salzbur, AT-5020 Salzburg, Austria. [Lener, Thomas; Gimona, Mario; Laner-Plamberger, Sandra; Schallmoser, Katharina; Rohde, Eva] Salzburger Landeskliniken GesmbH SALK, Univ Hosp, Dept Blood Grp Serol & Transfus Med, Salzburg, Austria. [Boerger, Verena; Goergens, Andre; Horn, Peter A.; Giebel, Bernd] Univ Duisburg Essen, Univ Hosp Essen, Inst Transfus Med, Essen, Germany. [Buzas, Edit] Semmelweis Univ, Dept Genet Cell & Immunobiol, H-1085 Budapest, Hungary. [Camussi, Giovanni] Univ Turin, Dept Med Sci, Ctr Mol Biotechnol, Turin, Italy. [Chaput, Nathalie] INSERM, CNRS,US23, Lab Immunomonitoring Oncol, UMS 3655, Villejuif, France. [Chaput, Nathalie; Thery, Clotilde] Inst Gustave Roussy, Ctr Clin Invest Biotherapy CICBT 1248, Villejuif, France. [Chatterjee, Devasis; Quesenberry, Peter] Rhode Isl Hosp, Div Hematol & Oncol, Providence, RI USA. [Chatterjee, Devasis; Quesenberry, Peter] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA. [Court, Felipe A.] Pontificia Univ Catolica Chile, Fac Biol, Dept Physiol, Santiago, Chile. [del Portillo, Hernando A.] Univ Barcelona, Hosp Clin, ICREA Barcelona Ctr Int Hlth Res CRESIB, Barcelona, Spain. [del Portillo, Hernando A.] Inst Invest Germans Trias & Pujol IGTP, Badalona, Spain. [O'Driscoll, Lorraine] Trinity Coll Dublin, Sch Pharm & Pharmaceut Sci, Dublin 2, Ireland. [O'Driscoll, Lorraine] Trinity Coll Dublin, Trinity Biomed Sci Inst, Dublin 2, Ireland. [Fais, Stefano] Natl Inst Hlth ISS, Dept Therapeut Res & Med Evaluat, Antitumor Drugs Sect, Rome, Italy. [Falcon-Perez, Juan M.] Bizkaia Technol Pk, CIBERehd, CIC bioGUNE, Metabol Unit, Derio, Spain. [Falcon-Perez, Juan M.] Ikerbasque, Basque Fdn Sci, E-48011 Bilbao, Spain. [Felderhoff-Mueser, Ursula] Univ Duisburg Essen, Univ Hosp Essen, Dept Paediat 1, Neonatol, Essen, Germany. [Fraile, Lorenzo] Univ Lleida, ETSEA, Dept Anim Prod, Lleida, Spain. [Gho, Yong Song] Pohang Univ Sci & Technol, Dept Life Sci, Pohang, South Korea. [Gupta, Ramesh C.] Univ Louisville, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. [Gupta, Ramesh C.] Univ Louisville, James Graham Brown Canc Ctr, Louisville, KY 40292 USA. [Hendrix, An] Ghent Univ Hosp, Dept Radiat Oncol & Expt Canc Res, Lab Expt Canc Res, Ghent, Belgium. [Hermann, Dirk M.] Univ Duisburg Essen, Dept Neurol, Univ Hosp Essen, Essen, Germany. [Hill, Andrew F.] La Trobe Univ, La Trobe Inst Mol Sci, Dept Biochem & Genet, Melbourne, Vic, Australia. [Hochberg, Fred] Massachusetts Gen Hosp, Boston, MA 02114 USA. [de Kleijn, Dominique] NUS, YLL Sch Med, Dept Surg, Singapore, Singapore. [Kordelas, Lambros] Univ Duisburg Essen, Univ Hosp Essen, Dept Bone Marrow Transplantat, Essen, Germany. [Kramer, Boris W.] Maastricht Univ, Med Ctr, Sch Oncol & Dev Biol, Expt Perinatol Neonatol,Sch Mental Hlth & Neurosc, NL-6200 MD Maastricht, Netherlands. [Kraemer-Albers, Eva-Maria] Johannes Gutenberg Univ Mainz, Mol Cell Biol & Focus Program Translat Neurosci, D-55122 Mainz, Germany. [Laitinen, Saara] Finnish Red Cross & Blood Transfus Serv, Res & Cell Serv, SF-00310 Helsinki, Finland. [Leonardi, Tommaso; Pluchino, Stefano] Univ Cambridge, Wellcome Trust Med Res Council, Dept Clin Neurosci, Div Stem Cell Neurobiol,Stem Cell Inst, Cambridge, England. [Leonardi, Tommaso] European Bioinformat Inst EMBL EBI, European Mol Biol Lab, Cambridge, England. [Lorenowicz, Magdalena J.] Univ Med Ctr, Ctr Mol Med, Dept Cell Biol, Utrecht, Netherlands. [Lim, Sai Kiang] Agcy Sci Technol & Res, Inst Med Biol, Singapore, Singapore. [Lotvall, Jan] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Krefting Res Ctr, Gothenburg, Sweden. [Maguire, Casey A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Marcilla, Antonio] Univ Valencia, Fac Farm, Dept Biol Celular & Parasitol, E-46010 Valencia, Spain. [Marcilla, Antonio] Univ Valencia, Hlth Res Inst La Fe, Joint Res Unit Endocrinol Nutr & Clin Dietet, Valencia, Spain. [Nazarenko, Irina] Univ Freiburg, Inst Environm Hlth Sci & Hosp Infect Control, Med Ctr, D-79106 Freiburg, Germany. [Ochiya, Takahiro] Natl Canc Ctr, Res Inst, Div Mol & Cellular Med, Tokyo 104, Japan. [Patel, Tushar] Mayo Clin, Dept Transplantat, Jacksonville, FL 32224 USA. [Patel, Tushar] Mayo Clin, Dept Canc Biol, Jacksonville, FL 32224 USA. [Pedersen, Shona] Aalborg Univ, Aalborg Univ Hosp, Dept Clin Biochem, Cardiovasc Res Ctr, Aalborg, Denmark. [Pocsfalvi, Gabriella] CNR, Inst Biosci & BioResources, Mass Spectrometry & Prote, Naples, Italy. [Reischl, Ilona G.] Inst Surveillance, Austrian Agcy Hlth & Food Safety,Inst Uberwachung, Fed Off Safety Hlth Care,AGES Agentur Gesundheit, BASG Bundesamt Sicherheit Gesundheitswesen, Vienna, Austria. [Rivera, Francisco J.] Paracelsus Med Univ, Spinal Cord Injury & Tissue Regenerat Ctr Salzbur, Inst Mol Regenerat Med, Salzburg, Austria. [Sanzenbacher, Ralf] Fed Inst Vaccines & Biomed, Paul Ehrlich Inst, Langen, Germany. [Slaper-Cortenbach, Ineke] Univ Med Ctr Utrecht, Dept Clin Pharm, Cell Therapy Facil, Utrecht, Netherlands. [Strunk, Dirk] Paracelsus Med Univ, Spinal Cord Injury & Tissue Regenerat Ctr Salzbur, Expt & Clin Cell Therapy Inst, Salzburg, Austria. [Tonn, Torsten] German Red Cross Blood Donat Serv North East, Inst Transfus Med Dresden, Dresden, Germany. [Vader, Pieter] Univ Med Ctr Utrecht, Lab Clin Chem & Hematol, Utrecht, Netherlands. [Vader, Pieter; El Andaloussi, Samir] Univ Oxford, Dept Physiol Anat & Genet, Oxford, England. [van Balkom, Bas W. M.] Univ Med Ctr Utrecht, Dept Hypertens & Nephrol, Utrecht, Netherlands. [Wauben, Marca] Univ Utrecht, Fac Vet Med, Dept Biochem & Cell Biol, Utrecht, Netherlands. [El Andaloussi, Samir] Karolinska Inst, Dept Lab Med, Stockholm, Sweden. [Thery, Clotilde] Inst Curie, INSERM, U932, Paris, France. RP Rohde, E (reprint author), Paracelsus Med Univ, Spinal Cord Injury & Tissue Regenerat Ctr Salzbur, AT-5020 Salzburg, Austria. EM e.rohde@salk.at; bernd.giebel@uk-essen.de RI Gorgens, Andre/C-3835-2016; Nazarenko, Irina/E-5714-2010; Fais, Stefano/J-8638-2016; Falcon-Perez, Juan/F-5920-2011; thery, clotilde/F-6373-2013 OI Vader, Pieter/0000-0002-7059-8920; Gorgens, Andre/0000-0001-9198-0857; Rivera, Francisco J./0000-0001-7895-6318; Leonardi, Tommaso/0000-0002-4449-1863; Camussi, Giovanni/0000-0003-2795-232X; Strunk, Dirk/0000-0003-1810-867X; Marcilla, Antonio/0000-0003-0004-0531; Fais, Stefano/0000-0001-9060-2766; thery, clotilde/0000-0001-8294-6884 FU european COST action [BM1202, ME-HaD] FX The authors have not received any funding or benefits from industry to conduct this study. The authors acknowledge the european COST action for supporting the European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD, BM1202, www.cost.eu/COST_Actions/BMBS/Actions/BM1202) who funded publication of this work. NR 311 TC 51 Z9 51 U1 12 U2 44 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2001-3078 J9 J EXTRACELL VESICLES JI J. Extracell. Vesicles PY 2015 VL 4 AR 30087 DI 10.3402/jev.v4.30087 PG 31 WC Cell Biology SC Cell Biology GA DA7WZ UT WOS:000368017400001 PM 26725829 ER PT J AU Suemoto, CK Ismail, S Correa, PCRP Zaina, F Jerves, T Pesantez, L Germani, ACCG Zaina, F dos Santos, ACS Ferreira, RJD Singh, P Paulo, JV Matsubayashi, SR Vidor, LP Andretta, G Tomas, R Illigens, BMW Fregni, F AF Suemoto, Claudia Kimie Ismail, Sherine Rodrigues Pinto Correa, Paulo Cesar Zaina, Fabio Jerves, Teodoro Pesantez, Laura Camargo Goncalves Germani, Ana Claudia Zaina, Fabio Soares dos Santos Junior, Augusto Cesar de Oliveira Ferreira, Ricardo Jorge Singh, Priyamvada Paulo, Judy Vicente Matsubayashi, Suely Reiko Vidor, Liliane Pinto Andretta, Guilherme Tomas, Rita Illigens, Ben M. W. Fregni, Felipe TI Five-year review of an international clinical research-training program SO ADVANCES IN MEDICAL EDUCATION AND PRACTICE LA English DT Review DE education; distance learning; biomedical research; critical thinking; e-learning ID EVIDENCE-BASED MEDICINE; STUDENTS; ENVIRONMENT; CHALLENGES; EDUCATION; SOCIETY; LECTURE; TRIALS AB The exponential increase in clinical research has profoundly changed medical sciences. Evidence that has accumulated in the past three decades from clinical trials has led to the proposal that clinical care should not be based solely on clinical expertise and patient values, and should integrate robust data from systematic research. As a consequence, clinical research has become more complex and methods have become more rigorous, and evidence is usually not easily translated into clinical practice. Therefore, the instruction of clinical research methods for scientists and clinicians must adapt to this new reality. To address this challenge, a global distance-learning clinical research-training program was developed, based on collaborative learning, the pedagogical goal of which was to develop critical thinking skills in clinical research. We describe and analyze the challenges and possible solutions of this course after 5 years of experience (2008-2012) with this program. Through evaluation by students and faculty, we identified and reviewed the following challenges of our program: 1) student engagement and motivation, 2) impact of heterogeneous audience on learning, 3) learning in large groups, 4) enhancing group learning, 5) enhancing social presence, 6) dropouts, 7) quality control, and 8) course management. We discuss these issues and potential alternatives with regard to our research and background. C1 [Suemoto, Claudia Kimie; Ismail, Sherine; Rodrigues Pinto Correa, Paulo Cesar; Zaina, Fabio; Jerves, Teodoro; Pesantez, Laura; Camargo Goncalves Germani, Ana Claudia; Zaina, Fabio; Soares dos Santos Junior, Augusto Cesar; de Oliveira Ferreira, Ricardo Jorge; Singh, Priyamvada; Paulo, Judy Vicente; Matsubayashi, Suely Reiko; Vidor, Liliane Pinto; Andretta, Guilherme; Tomas, Rita; Illigens, Ben M. W.; Fregni, Felipe] Harvard Univ, Sch Med, Principles & Practice Clin Res PPCR,Dept Phys Med, Collaborat Learning Clin Res Program,Spaulding Re, Boston, MA 02129 USA. [Suemoto, Claudia Kimie; Ismail, Sherine; Rodrigues Pinto Correa, Paulo Cesar; Zaina, Fabio; Jerves, Teodoro; Pesantez, Laura; Camargo Goncalves Germani, Ana Claudia; Zaina, Fabio; Soares dos Santos Junior, Augusto Cesar; de Oliveira Ferreira, Ricardo Jorge; Singh, Priyamvada; Paulo, Judy Vicente; Matsubayashi, Suely Reiko; Vidor, Liliane Pinto; Andretta, Guilherme; Tomas, Rita; Illigens, Ben M. W.; Fregni, Felipe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02129 USA. [Suemoto, Claudia Kimie] Univ Sao Paulo, Sch Med, Discipline Geriatr, Dept Internal Med, Sao Paulo, Brazil. [Ismail, Sherine] King Saud bin Abdulaziz Univ Hlth Sci, King Abdullah Int Med Res Ctr, King Khalid Hosp, NGHNGHA,Pharmaceut Care Dept, Jeddah, Saudi Arabia. [Rodrigues Pinto Correa, Paulo Cesar] Univ Fed Ouro Preto, Sch Med, Dept Internal Med, Discipline Internal Med & Med Semiol, Ouro Preto, Brazil. [Rodrigues Pinto Correa, Paulo Cesar] Ctr Univ Belo Horizonte Uni BH, Dept Internal Med, Discipline Pneumol, Belo Horizonte, MG, Brazil. [Zaina, Fabio] Canadian Ctr Adv Eye Therapeut, Mississauga, ON, Canada. [Camargo Goncalves Germani, Ana Claudia] Univ Sao Paulo, Sch Med, Dept Prevent Med, Sao Paulo, Brazil. [Zaina, Fabio] Italian Sci Spine Inst ISICO, Milan, Italy. [Soares dos Santos Junior, Augusto Cesar] Hosp Osvaldo Rezende Franco, Betim, Brazil. [Soares dos Santos Junior, Augusto Cesar] Univ Fed Minas Gerais, Nucleo Avaliacao Tecnol Saude, Belo Horizonte, MG, Brazil. [de Oliveira Ferreira, Ricardo Jorge] Centro Hosp & Univ Coimbra, Dept Rheumatol, Coimbra, Portugal. [Singh, Priyamvada] St Vincent Hosp, Dept Internal Med, Worcester, MA 01604 USA. [Paulo, Judy Vicente] Portuguese Inst Oncol, Coimbra, Portugal. [Matsubayashi, Suely Reiko] Univ Sao Paulo, Sch Med, Acupuncture Ctr, Orthoped & Traumatol Inst, Sao Paulo, Brazil. [Vidor, Liliane Pinto] Univ Fed Rio Grande do Sul, Fac Med, Dept Med Sci, Porto Alegre, RS, Brazil. [Andretta, Guilherme] Quintiles Transnat, Sao Paulo, Brazil. [Tomas, Rita] Ctr Hosp Lisboa Cent, EPE, Hosp Curry Cabral, Dept Phys Med & Rehabil, Lisbon, Portugal. [Illigens, Ben M. W.; Fregni, Felipe] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Fregni, Felipe] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Fregni, Felipe] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Fregni, F (reprint author), Harvard Univ, Sch Med, Principles & Practice Clin Res PPCR,Dept Phys Med, Collaborat Learning Clin Res Program,Spaulding Re, 79-96 13th St, Boston, MA 02129 USA. EM fregni.felipe@mgh.harvard.edu RI Santos Junior, Augusto Cesar/C-1802-2013; Suemoto, Claudia/C-7218-2012; OI Santos Junior, Augusto Cesar/0000-0001-5864-2338; Suemoto, Claudia/0000-0002-5942-4778; Zaina, Fabio/0000-0002-1256-5362 NR 42 TC 1 Z9 1 U1 0 U2 1 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1179-7258 J9 Adv Med Educ Pract JI Adv. Med. Educ. Pract. PY 2015 VL 6 BP 249 EP 257 DI 10.2147/AMEP.S66627 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA DA5OK UT WOS:000367852200002 PM 25878518 ER PT J AU Fujikawa, DG AF Fujikawa, Denson G. TI The Role of Excitotoxic Programmed Necrosis in Acute Brain Injury SO COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL LA English DT Review DE Excitotoxicity; Necrosis; Programmed cell death; NMDA receptor ID APOPTOSIS-INDUCING FACTOR; INTERNUCLEOSOMAL DNA CLEAVAGE; ELECTRON-MICROSCOPIC FINDINGS; POLY(ADP-RIBOSE) PAR POLYMER; TRANSIENT CEREBRAL-ISCHEMIA; HIPPOCAMPAL NEURONAL DEATH; INDUCED STATUS EPILEPTICUS; NMDA-RECEPTOR ACTIVATION; CELL-DEATH; CYTOCHROME-C AB Excitotoxicity involves the excessive release of glutamate from presynaptic nerve terminals and from reversal of astrocytic glutamate uptake, when there is excessive neuronal depolarization. N-methyl-D-aspartate (NMDA) receptors, a subtype of glutamate receptor, are activated in postsynaptic neurons, opening their receptor-operated cation channels to allow Ca2+ influx. The Ca2+ influx activates two enzymes, calpain I and neuronal nitric oxide synthase (nNOS). Calpain I activation produces mitochondrial release of cytochrome c (cyt c), truncated apoptosis-inducing factor (tAIF) and endonuclease G (endoG), the lysosomal release of cathepsins B and D and DNase II, and inactivation of the plasma membrane Na+-Ca2+ exchanger, which add to the buildup of intracellular Ca2+. tAIF is involved in large-scale DNA cleavage and cyt c may be involved in chromatin condensation; endoG produces internucleosomal DNA cleavage. The nuclear actions of the other proteins have not been determined. nNOS forms nitric oxide (NO), which reacts with superoxide (O-2(-)) to form peroxynitrite (ONOO-). These free radicals damage cellular membranes, intracellular proteins and DNA. DNA damage activates poly(ADPribose) polymerase-1 (PARP-1), which produces poly(ADP-ribose) (PAR) polymers that exit nuclei and translocate to mitochondrial membranes, also releasing AIF. Poly(ADP-ribose) glycohydrolase hydrolyzes PAR polymers into ADP-ribose molecules, which translocate to plasma membranes, activating melastatin-like transient receptor potential 2 (TRPM-2) channels, which open, allowing Ca2+ influx into neurons. NADPH oxidase (NOX1) transfers electrons across cellular membranes, producing O-2(-). The result of these processes is neuronal necrosis, which is a programmed cell death that is the basis of all acute neuronal injury in the adult brain. Fujikawa. Published by Elsevier B.V. on behalf of the Research Network of Computational and Structural Biotechnology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). C1 [Fujikawa, Denson G.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. RP Fujikawa, DG (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. EM dfujikaw@ucla.edu NR 82 TC 13 Z9 16 U1 3 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2001-0370 J9 COMPUT STRUCT BIOTEC JI Comp. Struct. Biotechnol. J.. PY 2015 VL 13 BP 212 EP 221 DI 10.1016/j.csbj.2015.03.004 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA DA4EJ UT WOS:000367752600026 PM 25893083 ER PT J AU Furlong, D Carroll, DL Finn, C Gay, D Gryglik, C Donahue, V AF Furlong, Donna Carroll, Diane L. Finn, Cynthia Gay, Diane Gryglik, Christine Donahue, Vivian TI Comparison of Temporal to Pulmonary Artery Temperature in Febrile Patients SO DIMENSIONS OF CRITICAL CARE NURSING LA English DT Article DE Fever; Temperature measurement; Temporal artery thermometer ID BODY-TEMPERATURE; ADULT; THERMOMETER; ACCURACY; SEPSIS; CORE AB Background: As a routine part of clinical care, temperature measurement is a key indicator of illness. With the criterion standard of temperature measurement from the pulmonary artery catheter thermistor (PAT), which insertion of PAT carries significant risk to the patient, a noninvasive method that is accurate and precise is needed. Objectives: The purpose of this study was to measure the precision and accuracy of 2 commonly used methods of collecting body temperature: PAT considered the criterion standard and the temporal artery thermometer (TAT) in those patients with a temperature greater than 100.4 degrees F. Methods: This is a repeated-measures design with each patient with a PAT in the intensive care unit acting as their own control to investigate the difference in PAT readings and readings from TAT in the core mode. Accuracy and precision were analyzed. Results: There were 60 subjects, 41 males and 19 females, with mean age of 60.8 years, and 97% (n = 58) were post-cardiac surgery. There was a statistically significant difference between PAT and TAT (101.0 degrees F [SD, 0.5 degrees F] vs 100.5 degrees F [SD, 0.8 degrees F]; bias, -0.49 degrees F; P < .001). Differences in temperature between the 2 methods were clinically significant (ie, >0.9 degrees F different) in 15 of 60 cases (25%). No TAT measurements were 0.9F greater than the corresponding PAT measurement (0%; 95% confidence interval, 0%-6%). Discussion: These data demonstrate the accuracy of TAT when compared with PAT in those with temperatures of 100.4 degrees F or greater. This study demonstrates that TAT set to core mode is accurate with a 0.5 degrees F lower temperature than PAT. There was 25% in variability in precision of TAT. C1 [Furlong, Donna; Finn, Cynthia; Gay, Diane; Gryglik, Christine; Donahue, Vivian] Massachusetts Gen Hosp, Cardiac Surg Intens Care Unit, Boston, MA 02114 USA. [Carroll, Diane L.] Massachusetts Gen Hosp, Munn Ctr Nursing Res, Boston, MA 02114 USA. RP Carroll, DL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM dcarroll3@partners.org NR 21 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0730-4625 EI 1538-8646 J9 DIMENS CRIT CARE NUR JI Dimens. Crit. Care Nurs. PD JAN-FEB PY 2015 VL 34 IS 1 BP 47 EP 52 DI 10.1097/DCC.0000000000000090 PG 6 WC Nursing SC Nursing GA DA4UA UT WOS:000367795300006 PM 25470268 ER PT J AU Zeidler, MR Santiago, V Dzierzewski, JM Mitchell, MN Santiago, S Martin, JL AF Zeidler, Michelle R. Santiago, Vicente Dzierzewski, Joseph M. Mitchell, Michael N. Santiago, Silverio Martin, Jennifer L. TI Predictors of Obstructive Sleep Apnea on Polysomnography after a Technically Inadequate or Normal Home Sleep Test SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE home sleep test; obstructive sleep apnea; polysomnography ID PREVALENCE; DIAGNOSIS AB Study Objectives: Home sleep testing (HST) is an accepted alternative to polysomnography (PSG) for diagnosing obstructive sleep apnea (OSA) in high-risk populations. Clinical guidelines recommend PSG in cases where the HST is technically inadequate (TI) or fails to establish the diagnosis of OSA in patients with high pretest probability. This retrospective study evaluated predictors of OSA on PSG within patients who had a TI or normal HST. Methods: Electronic medical records were reviewed on 1,157 patients referred for HST at our sleep center. Two hundred thirty-eight patients had a TI or normal HST with subsequent PSG. Age, BMI, Epworth score, HST result, and PSG-based apnea-hypopnea index (AHI) were abstracted. Results: Two hundred thirty-eight consecutive patients with either a normal HST (n = 127) or TI HST (n = 111) underwent subsequent PSG. Of 127 who had a normal HST, 76% had a normal PSG and 24% had OSA (23 mild, 6 moderate, 1 severe). Of 111 who had a TI HST, 29% had a normal PSG and 71% had OSA (43 mild, 19 moderate, 17 severe). Individuals younger than 50 years old with a normal HST were more likely to have a normal PSG. Older age predicted diagnosis of OSA on PSG among individuals with a TI HST. Conclusion: In this retrospective analysis of a clinical sample, when the HST is interpreted as normal in a younger patient population, the subsequent PSG is likewise normal in majority of the patients, although significant OSA is sometimes discovered. When a HST is read as TI, the majority of patients have OSA. C1 [Zeidler, Michelle R.; Santiago, Silverio] VA Greater Los Angeles Healthcare Syst, Pulm Crit Care & Sleep Med, Los Angeles, CA USA. [Zeidler, Michelle R.; Dzierzewski, Joseph M.; Martin, Jennifer L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Santiago, Vicente] VA Cent Calif Healthcare Syst, Fresno, CA USA. [Santiago, Vicente] Univ Calif San Francisco, Fresno Med Educ Program, San Francisco, CA 94143 USA. [Dzierzewski, Joseph M.; Mitchell, Michael N.; Martin, Jennifer L.] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. RP Zeidler, MR (reprint author), UCLA Med Ctr, West Los Angeles VA, Pulm & Crit Care, 10833 Le Conte Ave,CHS 37-131, Los Angeles, CA 90095 USA. EM mzeidler@mednet.ucla.edu FU VA Greater Los Angeles Healthcare System Sleep Medicine Fellowship Program; VA Rehabilitation Research and Development [1RX000135-01]; VA Greater Los Angeles Healthcare System Geriatric Research, Education and Clinical Center; UCLA Claude Pepper Older Americans Independence Center [5P30AG028748]; NIH/NCATS UCLA [CTSI UL1TR000124]; Research Service of the VA Greater Los Angeles Healthcare System; Equinox Fitness FX This was not an industry supported study. Supported by: VA Greater Los Angeles Healthcare System Sleep Medicine Fellowship Program, VA Rehabilitation Research and Development 1RX000135-01 (Martin) the VA Greater Los Angeles Healthcare System Geriatric Research, Education and Clinical Center, UCLA Claude Pepper Older Americans Independence Center 5P30AG028748 (Dzierzewski) and NIH/NCATS UCLA CTSI UL1TR000124 (Dzierzewski), and Research Service of the VA Greater Los Angeles Healthcare System. Dr. Martin has received research support from Equinox Fitness. The other author have indicated no financial conflicts of interest. NR 14 TC 1 Z9 1 U1 2 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 2015 VL 11 IS 11 BP 1313 EP 1318 DI 10.5664/jcsm.5194 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA DA1UM UT WOS:000367581000010 PM 26156951 ER PT J AU Watson, NF Morgenthaler, T Chervin, R Carden, K Kirsch, D Kristo, D Malhotra, R Martin, J Ramar, K Rosen, I Weaver, T Wise, M AF Watson, Nathaniel F. Morgenthaler, Timothy Chervin, Ronald Carden, Kelly Kirsch, Douglas Kristo, David Malhotra, Raman Martin, Jennifer Ramar, Kannan Rosen, Ilene Weaver, Terri Wise, Merrill CA Amer Acad Sleep Med Board TI Confronting Drowsy Driving: The American Academy of Sleep Medicine Perspective SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE drowsy driving; sleep deprivation; undiagnosed; sleep disorders AB Drowsy driving is a serious public health concern which is often difficult for individual drivers to identify. While it is important for drivers to understand the causes of drowsy driving, there is still insufficient scientific knowledge and public education to prevent drowsy driving. As a result, the AASM is calling upon institutions and policy makers to increase public awareness and improve education on the issue, so our society can better recognize and prevent drowsy driving. The AASM has adopted a position statement to educate both healthcare providers and the general public about drowsy driving risks and countermeasures. C1 [Watson, Nathaniel F.] Univ Washington, Sleep Disorders Ctr, Seattle, WA 98195 USA. [Morgenthaler, Timothy] Mayo Clin, Mayo Ctr Sleep Med, Rochester, MN USA. [Chervin, Ronald] Univ Michigan, Sleep Disorders Ctr, Ann Arbor, MI 48109 USA. [Carden, Kelly] St Thomas Sleep Specialists, Nashville, TN USA. [Kirsch, Douglas] Carolinas Healthcare Med Grp Sleep Serv, Charlotte, NC USA. [Kristo, David] Univ Pittsburgh, Pittsburgh, PA USA. [Malhotra, Raman] SLUCare Sleep Disorders Ctr, St Louis, MO USA. [Malhotra, Raman] St Louis Univ, Dept Neurol, St Louis, MO 63103 USA. [Martin, Jennifer] Vet Affairs Greater Los Angeles Hlth Syst, North Hills, CA USA. [Ramar, Kannan] Mayo Clin, Div Pulm Sleep Crit Care, Rochester, MN USA. [Rosen, Ilene] Penn Sleep Ctr, Philadelphia, PA USA. [Rosen, Ilene] Ctr Sleep, Philadelphia, PA USA. [Weaver, Terri] Univ Illinois, Coll Nursing, Chicago, IL USA. [Wise, Merrill] Methodist Healthcare Sleep Disorders Ctr, Memphis, TN USA. RP Watson, NF (reprint author), 2510 N Frontage Rd, Darien, IL 60561 USA. EM research@aasmnet.org FU Tera, Inc.; Jazz FX This was not an industry supported study. Dr. Chervin is on the advisory board of the not-for-profit SweetDreamzzz. Dr. Weaver has received research support form Tera, Inc., and Jazz. The other authors have indicated no financial conflicts of interest. NR 5 TC 2 Z9 2 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 2015 VL 11 IS 11 BP 1335 EP 1336 DI 10.5664/jcsm.5200 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA DA1UM UT WOS:000367581000013 ER PT J AU Eng, KJ Quraishi, SA AF Eng, Kristen J. Quraishi, Sadeq A. TI Changes in Vitamin D Status after Nasal Continuous Positive Airway Pressure: Could Alterations in Systemic Inflammatory Markers Explain These Observations? SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Letter C1 [Eng, Kristen J.; Quraishi, Sadeq A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Quraishi, Sadeq A.] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. RP Quraishi, SA (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRJ 402, Boston, MA 02114 USA. EM squraishi@mgh.harvard.edu NR 4 TC 1 Z9 1 U1 0 U2 0 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 2015 VL 11 IS 12 BP 1471 EP 1471 AR PII jc-00347-15 DI 10.5664/jcsm.5294 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA DA1UT UT WOS:000367581700018 PM 26414982 ER PT J AU Sher, L AF Sher, Leo TI PARENTAL ALIENATION AND SUICIDE IN MEN SO PSYCHIATRIA DANUBINA LA English DT Article ID ADULT CHILDREN C1 [Sher, Leo] James J Peters Vet Adm Med Ctr, New York, NY USA. [Sher, Leo] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. RP Sher, L (reprint author), James J Peters Vet Adm Med Ctr, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM Leo.Sher@mssm.edu NR 10 TC 1 Z9 1 U1 2 U2 9 PU MEDICINSKA NAKLADA PI ZAGREB PA VLASKA 69, HR-10000 ZAGREB, CROATIA SN 0353-5053 J9 PSYCHIAT DANUB JI Psychiatr. Danub. PY 2015 VL 27 IS 3 BP 288 EP 289 PG 2 WC Psychiatry SC Psychiatry GA DA1WM UT WOS:000367586300013 PM 26400140 ER PT J AU Tootell, RB Echavarria, C Nasr, S AF Tootell, Roger B. Echavarria, Cesar Nasr, Shahin TI A problem of overlap SO VISUAL NEUROSCIENCE LA English DT Article DE fMRI; LOC; MT; MTc; Visual cortex ID TEMPORAL VISUAL AREA; MACAQUE EXTRASTRIATE CORTEX; MONKEY AOTUS-TRIVIRGATUS; HUMAN OCCIPITAL CORTEX; VISUOTOPIC ORGANIZATION; RETINOTOPIC ORGANIZATION; FUNCTIONAL-PROPERTIES; CYTOCHROME-OXIDASE; NONHUMAN-PRIMATES; PATTERN-ANALYSIS AB Here we propose that earlier-demonstrated details in the primate visual cortical map may account for an otherwise puzzling (and problematic) finding in the current human fMRI literature. Specifically, the well-known regions LO and MT(+) reportedly overlap in the human cortical visual map, when those two regions are localized using standard stimulus comparisons in conventional fMRI experiments. Here we describe evidence supporting the idea that the apparent functional overlap between LO and MT arises from a third area (the MT crescent: "MTc"), which is well known to surround posterior MT based on earlier histological, neuroanatomical, and electrophysiological studies in nonhuman primates. If we assume that MTc also exists in human visual cortex, and that it has a location and functional properties intermediate to those in LO and MT, simplistic modeling confirmed that this arrangement could produce apparent overlap between localizers for LO and MT in conventional fMRI maps in human visual cortex. C1 [Tootell, Roger B.; Echavarria, Cesar; Nasr, Shahin] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Tootell, Roger B.; Nasr, Shahin] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Echavarria, C (reprint author), Massachusetts Gen Hosp, Radiol MRI Div, 149 13th St, Charlestown, MA 02129 USA. EM cechavarria@g.harvard.edu NR 65 TC 0 Z9 0 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0952-5238 EI 1469-8714 J9 VISUAL NEUROSCI JI Visual Neurosci. PY 2015 VL 32 AR e001 DI 10.1017/S0952523814000340 PG 8 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA DA1RH UT WOS:000367572700001 PM 26239105 ER PT S AU Ben-Ari, A Hammond, K AF Ben-Ari, Alon Hammond, Kenric BE Bui, TX Sprague, RH TI Text Mining the EMR for Modeling and Predicting Suicidal Behavior Among US Veterans of the 1991 Persian Gulf War SO 2015 48TH HAWAII INTERNATIONAL CONFERENCE ON SYSTEM SCIENCES (HICSS) SE Proceedings of the Annual Hawaii International Conference on System Sciences LA English DT Proceedings Paper CT 48th Annual Hawaii International Conference on System Sciences (HICSS) CY JAN 05-08, 2015 CL Kauai, HI SP IEEE Comp Soc, Univ Hawaii, Shidler Coll Business, Univ Hawaii, Dept EE, Univ Hawaii, Informat Sci Program, ONR, AFOSR, Natl Sci Fdn, IEEE Syst Sci & Cybernet Soc, ACM, SIAM, IEEE Hawaii Sect, IEEE Control Syst Soc, IEEE Grp Informat Theory, IEEE Grp Automat Control, ARO, Reg Med Program Hawaii, Univ Hawaii, Coll Business Adm, Nasdaq ID EXTRACTION; RISK AB Suicide is an important public health problem and prominent among U.S. veterans and active duty troops. Prediction of suicide and suicide attempts is problematic because these are low-frequency events and traditional clinical screening approaches have a high false positive rate. Large clinical databases extracted from electronic health records permit study of suicidal behavior in larger populations than previously possible using sampling techniques. In addition to offering structured data, text search and classification methods can identify additional risk variables. Data extracted from clinical records of 250,000 veterans were modeled using machine learning methodology. To predict suicide attempts in this population over a 10 year period. In contrast to previously reported models, our results showed high specificity and a false positive rate of 0.5%, contrasting with other studies showing false positive rates exceeding 20%. The model showed lower specificity with a true positive rate of 27% and a false negative rate of 73%. These results suggest that a machine learning approach developed with large data sets can usefully supplement current approaches to prediction of suicidal behavior. C1 [Ben-Ari, Alon; Hammond, Kenric] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Ben-Ari, A (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. EM alon.benari@gmail.com; khammond@uw.edu NR 15 TC 0 Z9 0 U1 3 U2 5 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 1060-3425 BN 978-1-4799-7367-5 J9 P ANN HICSS PY 2015 BP 3168 EP U2073 DI 10.1109/HICSS.2015.382 PG 11 WC Computer Science, Information Systems; Computer Science, Theory & Methods; Operations Research & Management Science SC Computer Science; Operations Research & Management Science GA BE0LK UT WOS:000366264103034 ER PT S AU Jarvenpaa, SL Lanham, HJ AF Jarvenpaa, Sirkka L. Lanham, Holly J. BE Bui, TX Sprague, RH TI Introduction to the Inter-Organizational Collaborative Dynamics and Role of Information Technology Minitrack SO 2015 48TH HAWAII INTERNATIONAL CONFERENCE ON SYSTEM SCIENCES (HICSS) SE Proceedings of the Annual Hawaii International Conference on System Sciences LA English DT Proceedings Paper CT 48th Annual Hawaii International Conference on System Sciences (HICSS) CY JAN 05-08, 2015 CL Kauai, HI SP IEEE Comp Soc, Univ Hawaii, Shidler Coll Business, Univ Hawaii, Dept EE, Univ Hawaii, Informat Sci Program, ONR, AFOSR, Natl Sci Fdn, IEEE Syst Sci & Cybernet Soc, ACM, SIAM, IEEE Hawaii Sect, IEEE Control Syst Soc, IEEE Grp Informat Theory, IEEE Grp Automat Control, ARO, Reg Med Program Hawaii, Univ Hawaii, Coll Business Adm, Nasdaq C1 [Jarvenpaa, Sirkka L.] Univ Texas Austin, McCombs Sch Business, Austin, TX 78712 USA. [Lanham, Holly J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA. [Lanham, Holly J.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Jarvenpaa, SL (reprint author), Univ Texas Austin, McCombs Sch Business, Austin, TX 78712 USA. EM sirkka.jarvenpaa@mccombs.utexas.edu; lanham@uthscsa.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 1060-3425 BN 978-1-4799-7367-5 J9 P ANN HICSS PY 2015 BP 4355 EP 4355 DI 10.1109/HICSS.2015.521 PG 1 WC Computer Science, Information Systems; Computer Science, Theory & Methods; Operations Research & Management Science SC Computer Science; Operations Research & Management Science GA BE0LK UT WOS:000366264104058 ER PT S AU Leibowitz, ML Zhang, CZ Pellman, D AF Leibowitz, Mitchell L. Zhang, Cheng-Zhong Pellman, David BE Bassler, BL TI Chromothripsis: A New Mechanism for Rapid Karyotype Evolution SO ANNUAL REVIEW OF GENETICS, VOL 49 SE Annual Review of Genetics LA English DT Review; Book Chapter DE micronuclei; complex chromosomal rearrangement; chromosome bridge; nuclear envelope rupture; single-cell sequencing; genome evolution ID DOUBLE-MINUTE CHROMOSOMES; PERIPHERAL-BLOOD LYMPHOCYTES; COMMON FRAGILE SITES; HOMOGENEOUSLY STAINING REGIONS; DIHYDROFOLATE-REDUCTASE GENES; COPY-NUMBER ALTERATION; CANCER GENOMES; DNA-REPLICATION; MICRONUCLEI FREQUENCY; RING CHROMOSOMES AB Chromosomal rearrangements are generally thought to accumulate gradually over many generations. However, DNA sequencing of cancer and congenital disorders uncovered a new pattern in which multiple rearrangements arise all at once. The most striking example, chromothripsis, is characterized by tens or hundreds of rearrangements confined to a single chromosome or to local regions over a few chromosomes. Genomic analysis of chromothripsis and the search for its biological mechanism have led to new insights on how chromosome segregation errors can generate mutagenesis and changes to the karyotype. Here, we review the genomic features of chromothripsis and summarize recent progress on understanding its mechanism. This includes reviewing new work indicating that one mechanism to generate chromothripsis is through the physical isolation of chromosomes in abnormal nuclear structures (micronuclei). We also discuss connections revealed by recent genomic analysis of cancers between chromothripsis, chromosome bridges, and ring chromosomes. C1 [Leibowitz, Mitchell L.; Zhang, Cheng-Zhong; Pellman, David] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Zhang, Cheng-Zhong] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Leibowitz, Mitchell L.; Zhang, Cheng-Zhong; Pellman, David] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Zhang, Cheng-Zhong; Pellman, David] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Pellman, David] Howard Hughes Med Inst, Boston, MA 02115 USA. RP Pellman, D (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. EM mleibowitz@fas.harvard.edu; chengz@broadinstitute.org; david_pellman@dfci.harvard.edu FU Howard Hughes Medical Institute; NIGMS NIH HHS [GM083299-18, R01 GM083299] NR 173 TC 22 Z9 22 U1 1 U2 13 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4197 BN 978-0-8243-1249-7 J9 ANNU REV GENET JI Annu. Rev. Genet. PY 2015 VL 49 BP 183 EP 211 DI 10.1146/annurev-genet-120213-092228 PG 29 WC Genetics & Heredity SC Genetics & Heredity GA BE0XC UT WOS:000367291000009 PM 26442848 ER PT J AU Skogseth, RE Bronnick, K Pereira, JB Mollenhauer, B Weintraub, D Fladby, T Aarsland, D AF Skogseth, Ragnhild E. Bronnick, Kolbjorn Pereira, Joana B. Mollenhauer, Brit Weintraub, Daniel Fladby, Tormod Aarsland, Dag TI Associations between Cerebrospinal Fluid Biomarkers and Cognition in Early Untreated Parkinson's Disease SO JOURNAL OF PARKINSONS DISEASE LA English DT Article DE Parkinson disease; cerebrospinal fluid; Mild cognitive impairment; alpha-synuclein; amyloid beta-peptides; tau Proteins ID CSF AMYLOID-BETA; ALPHA-SYNUCLEIN; ALZHEIMERS-DISEASE; DEMENTIA; IMPAIRMENT; PROGRESSION; DECLINE; TAU; COHORT; RISK AB Background: Mild cognitive impairment and dementia are common, clinically important features of Parkinson's disease (PD). The underlying disease pathology is heterogeneous and not yet well characterized. Biomarkers for cognitive impairment in PD could aid in diagnostic and prognostic evaluation and in the development of new cognitive enhancing treatments. Objective: To examine the relationship between CSF markers and cognition in a large, multicenter, cohort study of early, untreated PD, and compare marker concentrations between PD patients with and without MCI and healthy, age-matched controls. Methods: 414 early, untreated PD (34% with mild cognitive impairment) and 189 healthy, cognitively intact controls with baseline neuropsychological testing and CSF abeta42, t-tau, p-tau181 and alpha-synuclein results were included. Multiple linear regression models were constructed with a composite cognition factor, or memory-, or visuospatial- or executive-attention domains as dependent variables, and CSF markers, demographic characteristics and MDS-UPDRS III score as predictors. Results: Lower alpha-synuclein was associated with reduced performance on the executive-attention domain and the composite cognition factor in the whole PD-group. Abeta42 was significantly decreased in PD with mild cognitive impairment compared with controls after adjusting for covariates, while values in PD without MCI were identical to healthy controls. Conclusions: The association between reduced CSF alpha-synuclein concentrations and cognition suggests that alpha-synuclein pathology contributes to early cognitive impairment in PD, in particular to executive-attentional dysfunction. Longitudinal analyses are needed to determine if this and other CSF biomarkers in early Parkinson's disease are associated with the risk of future cognitive decline and dementia. C1 [Skogseth, Ragnhild E.] Haraldsplass Deaconess Hosp, Kavli Res Ctr Geriatr & Dementia, N-5892 Bergen, Norway. [Skogseth, Ragnhild E.] Univ Bergen, Dept Clin Med, N-5020 Bergen, Norway. [Bronnick, Kolbjorn] Stavanger Univ Hosp, TIPS Reg Ctr Clin Res Psychosis, Stavanger, Norway. [Bronnick, Kolbjorn] Univ Stavanger, Fac Social Sci, Stavanger, Norway. [Pereira, Joana B.] Karolinska Inst H1, Dept Neurobiol Care Sci & Soc, Div Clin Geriatr, Huddinge, Sweden. [Mollenhauer, Brit] Univ Med Ctr Gottingen, Paracelsus Elena Klin, Gottingen, Germany. [Mollenhauer, Brit] Univ Med Ctr Gottingen, Dept Neuropathol, Gottingen, Germany. [Weintraub, Daniel] Univ Penn, Perelman Sch Med, Dept Psychiat & Neurol, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Fladby, Tormod] Akershus Univ Hosp, Dept Neurol, Lorenskog, Norway. [Fladby, Tormod] Univ Oslo, Inst Clin Med, N-0316 Oslo, Norway. [Aarsland, Dag] Karolinska Inst H1, Ctr Alzheimers Dis Res, Dept Neurobiol Care Sci & Soc, Div Neurogeriatr, Huddinge, Sweden. [Aarsland, Dag] Stavanger Univ Hosp, Dept Psychiat, Ctr Age Related Med, Stavanger, Norway. RP Skogseth, RE (reprint author), Haraldsplass Deaconess Hosp, Postboks 6165 Postterminal, N-5892 Bergen, Norway. EM ragnhild.skogseth@gmail.com OI Aarsland, Dag/0000-0001-6314-216X FU Swedish non-governmental and industry independent sources; Alzheimerfonden; Stiftelsen for alderssjukdomar; Loo och Hans Ostermans stiftelse; Lindhes Advokatbyra AB; TEVA-Pharma; BMBF; EU; Deutsche Parkinson Vereinigung; Michael J. Fox Foundation for Parkinson's Research; Stifterverband fur die deutsche Wissenschaft; Teva Pharmaceuticals; Novartis Pharmaceuticals; NINDS [P50 NS053488, R01NS065087]; NIA [RO1AG031348]; University of Pennsylvania; Lundbeck Inc.; Novartis; GE Healthcare; GlaxoSmithKline; Merck Serono FX Dr. Skogseth reports no disclosures. Dr. Bronnick reports no disclosures. Dr. Pereira has received a Marie Curie Intra-European Fellowship and project grants from Swedish non-governmental and industry independent sources; Alzheimerfonden, Stiftelsen for alderssjukdomar, Loo och Hans Ostermans stiftelse and Lindhes Advokatbyra AB. Dr. Mollenhauer is member of the executive steering committee of the Parkinson Progression Marker Initiative of the Michael J. Fox Foundation for Parkinson's Research. She has received independent research grants from TEVA-Pharma, and honoraria for consultancy from GE Healthcare, Roche, AbbVie, TEVA-Pharma, for presentations from GlaxoSmithKline, Orion Pharma, TEVA-Pharma and travel costs from TEVA-Pharma. She has received grants from the BMBF, EU, Deutsche Parkinson Vereinigung, Michael J. Fox Foundation for Parkinson's Research, Stifterverband fur die deutsche Wissenschaft, and has scientific collaborations with Roche, Ely Lilly, Covance/BioLegend and Biogen Idec. Dr. Weintraub is part of the scientific advisory boards: Commercial - Pfizer, CHDI, Teva Pharmaceuticals, Avanir Pharmaceuticals, Merck, Eli Lilly and Company, Biogen, Lundbeck Inc. He is part of the Editorial Board of Movement Disorders Journal and receives: Funding for Travel or Speaker Honoraria: Commercial - Teva Pharmaceuticals; Research Support, Commercial Entities: Novartis Pharmaceuticals, PI, 2011-; Research Support from Government Entities: NINDS, P50 NS053488, Investigator, 2007- NINDS, R01NS065087, Investigator, 2009- NIA, RO1AG031348, Investigator, 2008-; Research Support, Foundations and Societies: Michael J. Fox Foundation for Parkinson's Research, PI, 2009- 2011, Michael J. Fox Foundation for Parkinson's Research, PI, 2011- Michael J. Fox Foundation for Parkinson's Research, Investigator, 2011-; License Fee Payments, Technology or Inventions: Licensing fees from the University of Pennsylvania for licensing of Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease.; Dr. Fladby reports no disclosures. Dr. Aarsland serves on scientific advisory boards for Lundbeck Inc. and Merck Serono; has received funding for travel and speaker honoraria from Lundbeck Inc., Novartis, GE Healthcare, and GlaxoSmithKline; serves on the editorial boards of International Psychogeriatrics, Movement Disorders, and the Journal of Neurology, Neurosurgery, and Psychiatry; and receives research support from Lundbeck Inc. and Merck Serono. NR 26 TC 4 Z9 4 U1 2 U2 5 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 2015 VL 5 IS 4 BP 783 EP 792 DI 10.3233/JPD-150682 PG 10 WC Neurosciences SC Neurosciences & Neurology GA CZ7VL UT WOS:000367308200011 PM 26599300 ER PT J AU Shah, S Banh, ET Koury, K Bhatia, G Nandi, R Gulur, P AF Shah, Shalini Banh, Esther T. Koury, Katharine Bhatia, Gaurav Nandi, Roneeta Gulur, Padma TI Pain Management in Pregnancy: Multimodal Approaches SO PAIN RESEARCH AND TREATMENT LA English DT Review ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; LOW-BACK-PAIN; CARPAL-TUNNEL-SYNDROME; POSTERIOR PELVIC PAIN; ALTERNATIVE MEDICINE; RHEUMATOID-ARTHRITIS; INTRAUTERINE EXPOSURE; SPONTANEOUS-ABORTION; ACETAMINOPHEN USE; MILD ANALGESICS AB Nonobstetrical causes of pain during pregnancy are very common and can be incapacitating if not treated appropriately. Recent reports in the literature show that a significant percentage of pregnant women are treated with opioids during pregnancy. To address common pain conditions that present during pregnancy and the available pharmacological and nonpharmacological treatment options, for each of the pain conditions identified, a search using MEDLINE, PubMed, Embase, and Cochrane databases was performed. Thequality of the evidence was evaluated in the context of study design. This paper is a narrative summary of the results obtained from individual reviews. There were significant disparities in the studies in terms of design, research and methodology, and outcomes analyzed. There is reasonable evidence available for pharmacological approaches; however, these are also associated with adverse events. Evidence for nonpharmacological approaches is limited and hence their efficacy is unclear, although they do appear to be primarily safe. A multimodal approach using a combination of nonpharmacological and pharmacological options to treat these pain conditions is likely to have the most benefit while limiting risk. Research trials with sound methodology and analysis of outcome data are needed. C1 [Shah, Shalini; Banh, Esther T.; Gulur, Padma] Univ Calif Irvine, Dept Anesthesiol & Perioperat Care, Orange, CA 92868 USA. [Koury, Katharine; Bhatia, Gaurav; Nandi, Roneeta] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Gulur, P (reprint author), Univ Calif Irvine, Dept Anesthesiol & Perioperat Care, 333 City Blvd West,Suite 2150, Orange, CA 92868 USA. EM pgulur@yahoo.com NR 77 TC 0 Z9 0 U1 0 U2 1 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 2090-1542 EI 2090-1550 J9 PAIN RES TREAT JI Pain Res. Treat. PY 2015 AR UNSP 987483 DI 10.1155/2015/987483 PG 15 WC Clinical Neurology SC Neurosciences & Neurology GA CU6QI UT WOS:000363656900001 ER PT J AU Tanaka, M Roberts, JM Qi, J Bradner, JE AF Tanaka, Minoru Roberts, Justin M. Qi, Jun Bradner, James E. TI Inhibitors of emerging epigenetic targets for cancer therapy: a patent review (2010-2014) SO PHARMACEUTICAL PATENT ANALYST LA English DT Review ID BET BROMODOMAIN INHIBITION; HISTONE METHYLTRANSFERASE EZH2; FRAGMENT-BASED DISCOVERY; SMALL-MOLECULE INHIBITOR; MIXED-LINEAGE LEUKEMIA; MLL-FUSION LEUKEMIA; B-CELL LYMPHOMA; H3 LYSINE 27; SELECTIVE-INHIBITION; H3K79 METHYLATION AB Gene regulatory pathways comprise an emerging and active area of chemical probe discovery and investigational drug development. Emerging insights from cancer genome sequencing and chromatin biology have identified leveraged opportunities for development of chromatin-directed small molecules as cancer therapies. At present, only six agents in two epigenetic target classes have been approved by the US FDA, limited to treatment of hematological malignancies. Recently, new classes of epigenetic inhibitors have appeared in literatures. First-in-class compounds have successfully transitioned to clinical investigation, importantly also in solid tumors and pediatric malignancies. This review considers patent applications for small-molecule inhibitors of selected epigenetic targets from 2010 to 2014. Included are exemplary classes of chromatin-associated epigenomic writers (DOT1L and EZH2), erasers (LSD1) and readers (BRD4). C1 [Tanaka, Minoru; Roberts, Justin M.; Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Tanaka, Minoru; Bradner, James E.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Bradner, JE (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 360 Longwood Ave, Boston, MA 02215 USA. EM james_bradner@dfci.harvard.edu NR 212 TC 8 Z9 8 U1 2 U2 11 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 2046-8954 EI 2046-8962 J9 PHARM PAT ANAL JI Pharm. Pat. Anal. PY 2015 VL 4 IS 4 BP 261 EP 284 DI 10.4155/PPA.15.16 PG 24 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CU3AN UT WOS:000363395700003 PM 26174566 ER PT J AU Fan, L Goss, PE Strasser-Weippl, K AF Fan, Lei Goss, Paul E. Strasser-Weippl, Kathrin TI Current Status and Future Projections of Breast Cancer in Asia SO BREAST CARE LA English DT Review DE Breast cancer; Incidence; Epidemiology; Asia; Screening ID PERIOD-COHORT ANALYSIS; SOUTH-EAST ASIA; SCREENING-PROGRAM; RANDOMIZED-TRIAL; SELF-EXAMINATION; PACIFIC REGION; CHINESE WOMEN; SAUDI-ARABIA; RISK-FACTORS; EPIDEMIOLOGY AB Asia is the world's largest continent comprising about 3/5 of the human population. Breast cancer is the most common type of cancer and the second leading cause of cancer-related deaths among women in Asia, accounting for 39% of all breast cancers diagnosed worldwide. The incidence of breast cancer in Asia varies widely across the continent and is still lower than in Western countries, but the proportional contribution of Asia to the global breast cancer rates is increasing rapidly in parallel to the socioeconomic development. However, the mortality-to-incidence ratios are much higher for Asia than for Western countries. Most Asian countries are low- and middle-income countries (LMICs) where breast cancer presents at a younger age and a later stage, and where patients are more likely to die from the disease than those in Western countries. Moreover, diagnostic workup, treatment and palliative services are inadequate in most Asian LMICs. In this review, we present an overview of the breast cancer risk factors and epidemiology, control measures, and cancer care among Asian countries. (C) 2015 S. Karger GmbH, Freiburg C1 [Fan, Lei] Fudan Univ, Inst Biomed Sci, Shanghai Med Coll, Breast Canc Inst,Canc Hosp,Dept Oncol, Shanghai 200433, Peoples R China. [Goss, Paul E.] Global Canc Inst, Boston, MA USA. [Goss, Paul E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Strasser-Weippl, Kathrin] Wilhelminen Hosp, Ctr Oncol Hematol & Palliat Care, A-1160 Vienna, Austria. RP Strasser-Weippl, K (reprint author), Wilhelminen Hosp, Ctr Oncol Hematol & Palliat Care, Montleartstr 37, A-1160 Vienna, Austria. EM Kathrin.strasserweippl@gmail.com NR 77 TC 5 Z9 5 U1 2 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-3791 EI 1661-3805 J9 BREAST CARE JI Breast Care PY 2015 VL 10 IS 6 BP 372 EP 378 DI 10.1159/000441818 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CZ3IN UT WOS:000366997800003 PM 26989355 ER PT J AU Hirata, K Hogl, B Tan, EK Videnovic, A AF Hirata, Koichi Hoegl, Birgit Tan, Eng King Videnovic, Aleksandar TI Sleep Problems in Parkinson's Disease SO PARKINSONS DISEASE LA English DT Editorial Material C1 [Hirata, Koichi] Dokkyo Med Univ, Dept Neurol, Mibu, Tochigi 3210293, Japan. [Hoegl, Birgit] Med Univ Innsbruck, Dept Neurol, A-6020 Innsbruck, Austria. [Tan, Eng King] Singapore Gen Hosp, Dept Neurol, Singapore, Singapore. [Videnovic, Aleksandar] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Div Sleep Med, Boston, MA 02115 USA. RP Hirata, K (reprint author), Dokkyo Med Univ, Dept Neurol, Mibu, Tochigi 3210293, Japan. EM hirata@dokkyomed.ac.jp NR 6 TC 0 Z9 0 U1 0 U2 1 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-8083 EI 2042-0080 J9 PARKINSONS DIS-US JI Parkinsons Dis. PY 2015 AR 507948 DI 10.1155/2015/507948 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA CZ7IC UT WOS:000367272100001 ER PT J AU Borwankar, AU Willsey, BW Twu, A Hung, JJ Stover, RJ Wang, TYW Feldman, MD Milner, TE Truskett, TM Johnston, KP AF Borwankar, Ameya U. Willsey, Brian W. Twu, April Hung, Jessica J. Stover, Robert J. Wang, Tianyi W. Feldman, Marc D. Milner, Thomas E. Truskett, Thomas M. Johnston, Keith P. TI Gold nanoparticles with high densities of small protuberances on nanocluster cores with strong NIR extinction SO RSC ADVANCES LA English DT Article ID RAMAN-SCATTERING SERS; ONE-STEP SYNTHESIS; BIODEGRADABLE PLASMONIC NANOCLUSTERS; COLLOIDAL GOLD; OPTICAL-PROPERTIES; LIGHT-ABSORPTION; SHAPE EVOLUTION; PARTICLE-SIZE; NANOSTARS; CLUSTERS AB Plasmonic nanoparticles with sizes well below 100 nm and high near infrared ( NIR) extinction are of great interest in biomedical imaging. Herein we present similar to 60 nm Au nanoparticles with high NIR absorbance at wavelengths ranging from 700 nm to 1100 nm, which were synthesized under kinetic control. A high surface density of protuberances is grown on similar to 30 nm nanocluster cores, which are composed of similar to 10 nm primary particles. The high NIR extinction is produced by a combination of the close proximity of the primary particles in the cores, the high surface density of protuberances, and the high aspect ratio of the length of the protuberances to the diameter of the primary particles. When the Au precursor was reduced more slowly at a higher pH of 9.3, the growth was thermodynamically controlled and the nanocluster cores relaxed to spheres. This concept of self-assembly during reaction to change the morphology of nanoclusters and decorated nanoclusters, may be expected to be applicable to a wide variety of systems by balancing kinetic and thermodynamic control, along with the colloidal interactions. C1 [Borwankar, Ameya U.; Willsey, Brian W.; Twu, April; Hung, Jessica J.; Stover, Robert J.; Truskett, Thomas M.; Johnston, Keith P.] Univ Texas Austin, McKetta Dept Chem Engn, Austin, TX 78712 USA. [Wang, Tianyi W.; Milner, Thomas E.] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA. [Feldman, Marc D.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Feldman, Marc D.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Cardiol, San Antonio, TX 78229 USA. RP Johnston, KP (reprint author), Univ Texas Austin, McKetta Dept Chem Engn, Austin, TX 78712 USA. EM kpj@che.utexas.edu RI Truskett, Thomas/D-4624-2009 OI Truskett, Thomas/0000-0002-6607-6468 FU Welch Foundation [F-1319, F-1696]; NSF [CBET-0968038]; INSPIRE [1247945]; Veterans Hospital Administration Merit Grant FX This work is supported in part by the Welch Foundation (F-1319 (KPJ), F-1696 (TMT)), NSF CBET-0968038, INSPIRE 1247945 and the Veterans Hospital Administration Merit Grant. We would like to thank Dr Dwight Romanowicz from the Institute of Cellular and Molecular biology and Dr Shouliang Zhang from the Center for Nanomaterials both at the University of Texas for their assistance with the electron microscopy. NR 89 TC 1 Z9 1 U1 3 U2 11 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2046-2069 J9 RSC ADV JI RSC Adv. PY 2015 VL 5 IS 127 BP 104674 EP 104687 DI 10.1039/c5ra21712a PG 14 WC Chemistry, Multidisciplinary SC Chemistry GA CZ1KY UT WOS:000366865900008 ER PT J AU Vaid, M Singh, T Prasad, R Kappes, JC Katiyar, SK AF Vaid, Mudit Singh, Tripti Prasad, Ram Kappes, John C. Katiyar, Santosh K. TI Therapeutic intervention of proanthocyanidins on the migration capacity of melanoma cells is mediated through PGE(2) receptors and beta-catenin signaling molecules SO AMERICAN JOURNAL OF CANCER RESEARCH LA English DT Article DE Grape seed proanthocyanidins; melanoma; cell migration; prostaglandin E-2; PGE(2) receptors; beta-catenin; bioluminescence imaging; metastasis ID IN-VIVO; CUTANEOUS MELANOMA; COLORECTAL-CANCER; LUNG-CANCER; MOUSE SKIN; EXPRESSION; PHOTOCARCINOGENESIS; CARCINOGENESIS; ACTIVATION; MUTATIONS AB Melanoma is a highly aggressive form of skin cancer and a leading cause of death from skin diseases mainly due to its propensity to metastasis. Due to metastatic tendency, melanoma is often associated with activation of Wnt/beta-catenin signaling mechanism. Blocking beta-catenin activation may be a good strategy to block melanoma-associated mortality. We have shown earlier that grape seed proanthocyanidins (GSPs) inhibit melanoma cell migration via targeting cyclooxygenase-2 (COX-2) overexpression. Here we explored further whether inhibition of inflammatory mediators-mediated activation of beta-catenin by GSPs is associated with the inhibition of melanoma cell migration. Our study revealed that PGE(2) receptors (EP2 and EP4) agonists promote melanoma cell migration while PGE(2) receptor antagonist suppressed the migration capacity of melanoma cells. GSPs treatment inhibit butaprost (EP2 agonist) or Cay10580 (EP4 agonist) induced migration of melanoma cells. Western blot analysis revealed that GSPs reduced cellular accumulation of beta-catenin, and decreased the expressions of matrix metalloproteinase (MMP)-2, MMP-9 and MITF, downstream targets of beta-catenin in melanoma cells. GSPs also reduced the protein expressions of PI3K and p-Akt in the same set of experiment. To verify that beta-catenin is a specific molecular target of GSPs, we compared the effect of GSPs on cell migration of beta-catenin-activated (Mel1241) and beta-catenin-inactivated (Mel1011) melanoma cells. GSPs inhibit cell migration of Mel1241 cells but not of Mel1011 cells. Additionally, in vi bioluminescence imaging data indicate that dietary administration of GSPs (0.5%, w/w) in supplementation with AIN76A control diet inhibited the migration/extravasation of intravenously injected melanoma cells in lungs of immune-compromised nude mice, and that this effect of GSPs was associated with an inhibitory effect on the activation of beta-catenin and its downstream targets, such as MMPs, in lungs as a target organ. C1 [Vaid, Mudit; Singh, Tripti; Prasad, Ram; Katiyar, Santosh K.] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. [Kappes, John C.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Kappes, John C.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Kappes, John C.; Katiyar, Santosh K.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA. [Singh, Tripti; Prasad, Ram; Kappes, John C.; Katiyar, Santosh K.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. RP Katiyar, SK (reprint author), Univ Alabama Birmingham, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU National Institutes of Health (NIH) [CA166883]; Veterans Administration Merit Review Award [1I01BX001410]; Virology and Genetic Sequencing cores of the UAB Center for AIDS Research (CFAR) [P30AI-27767] FX This work was supported by grants from the National Institutes of Health (NIH, CA166883) and the Veterans Administration Merit Review Award (1I01BX001410) to S. K. K. This research also used the facilities supported by of the Virology and Genetic Sequencing cores of the UAB Center for AIDS Research (CFAR), P30AI- 27767. The funding agencies had no roles in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 1 Z9 1 U1 0 U2 0 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 2015 VL 5 IS 11 BP 3325 EP 3338 PG 14 WC Oncology SC Oncology GA CY8ZX UT WOS:000366698300005 PM 26807314 ER PT J AU Fulciniti, M Munshi, NC Martinez-Lopez, J AF Fulciniti, Mariateresa Munshi, Nikhil C. Martinez-Lopez, Joaquin TI Deep Response in Multiple Myeloma: A Critical Review SO BIOMED RESEARCH INTERNATIONAL LA English DT Review ID MINIMAL RESIDUAL DISEASE; STEM-CELL TRANSPLANTATION; FREE LIGHT-CHAIN; MULTIPARAMETER FLOW-CYTOMETRY; STRINGENT COMPLETE RESPONSE; PROGNOSTIC VALUE; AUTOLOGOUS TRANSPLANTATION; COMPLETE REMISSION; SURVIVAL BENEFIT; THERAPY AB Novel and more effective treatment strategies against multiple myeloma (MM) have significantly prolonged patients' survival and raised interest in the depth of response and its association with clinical outcome. Minimal residual disease (MRD) has emerged as one of the most relevant prognostic factors in MM and should be included in a new definition of complete response (CR). Although further standardization is still required, MRD monitoring should be applied in prospective clinical trials as a sensitive tool to compare and evaluate the efficacy of different treatment strategies, particularly in the consolidation and maintenance settings, and implement individualized therapy-monitoring approaches. Here, we review current definition of deep response in MM, advantages and limitations of current MRD assessment assays, clinical evidences for MRD monitoring as a prognostic tool for therapeutic decisions in MM, and challenges to develop uniform criteria for MRD monitoring. C1 [Fulciniti, Mariateresa; Munshi, Nikhil C.; Martinez-Lopez, Joaquin] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02215 USA. [Martinez-Lopez, Joaquin] Univ Madrid, Dept Hematol, Hosp 12 Octubre, Unidad CRIS,CNIO, Madrid, Spain. RP Fulciniti, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02215 USA. EM mariateresa_fulciniti@dfci.harvard.edu NR 55 TC 2 Z9 2 U1 0 U2 2 PU HINDAWI PUBLISHING CORP 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 2015 AR 832049 DI 10.1155/2015/832049 PG 7 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA CZ2OB UT WOS:000366943400001 ER PT J AU Johansen, KL AF Johansen, Kirsten L. TI The Frail Dialysis Population: A Growing Burden for the Dialysis Community SO BLOOD PURIFICATION LA English DT Article; Proceedings Paper CT 60th Annual Meeting of the Japanese-Society-for-Dialysis-Therapy CY JUN, 2015 CL Yokohama, JAPAN SP Japanese Soc Dialysis Therapy DE Frailty; Dialysis; End-stage renal disease ID STAGE RENAL-DISEASE; CHRONIC KIDNEY-DISEASE; PHYSICAL-ACTIVITY; HEMODIALYSIS-PATIENTS; BODY-COMPOSITION; MAINTENANCE HEMODIALYSIS; AMBULATORY PATIENTS; ASSOCIATION; MORTALITY; SURVIVAL AB Background: The dialysis population is aging worldwide. It is well known that patients on dialysis have limited functional status, but only recently has frailty been considered. Summary: The prevalence of frailty among patients on dialysis ranges from 3.4-to 10-fold higher than among community- dwelling elderly, depending on the method of assessing frailty and patient characteristics. Despite its high prevalence and the high overall mortality in the dialysis population, frailty is associated with higher mortality, independent of clinical and demographic characteristics and comorbidity. The prevalence of frailty among patients with nondialysis- dependent chronic kidney disease (CKD) is also high, and cross-sectional data suggest that the prevalence may increase as CKD progresses. Thus, interventions to improve frailty have the potential to improve quality of life and mortality. Although interventions to improve physical dysfunction have been successful in the population with end-stage renal disease, no studies have specifically targeted frail individuals. Therefore, the extent to which exercise or physical activity interventions are feasible among frail patients and can improve frailty urgently needs to be examined. In the meantime, providers should refer frail patients to physical therapists and encourage them to be more active if possible. In addition, more attention should be focused on the possibility that rehabilitation among patients with earlier stages of CKD could improve dialysis outcomes. Key Messages: Frailty is extremely common among patients on dialysis and is independently associated with adverse outcomes. Providers should take advantage of available resources to improve functioning in this population, and research should address the optimal strategy for addressing frailty, including timing of intervention. (C) 2015 S. Karger AG, Basel C1 [Johansen, Kirsten L.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA USA. RP Johansen, KL (reprint author), 111J San Francisco VA Med Ctr, Nephrol Sect, 4150 Clement St, San Francisco, CA 94127 USA. EM kirsten.johansen@ucsf.edu NR 34 TC 3 Z9 3 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0253-5068 EI 1421-9735 J9 BLOOD PURIFICAT JI Blood Purif. PY 2015 VL 40 IS 4 BP 288 EP 292 DI 10.1159/000441575 PG 5 WC Hematology; Urology & Nephrology SC Hematology; Urology & Nephrology GA CY9NX UT WOS:000366734700004 PM 26656296 ER PT J AU Al-Haddad, C Abdulaal, M Al-Moujahed, A Ervin, AM AF Al-Haddad, Christiane Abdulaal, Marwan Al-Moujahed, Ahmad Ervin, Ann-Margret TI Fornix-based versus limbal-based conjunctival trabeculectomy flaps for glaucoma SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID MITOMYCIN-C TRABECULECTOMY; COMBINED PHACOEMULSIFICATION; 2-SITE PHACOTRABECULECTOMY; FILTERING SURGERY; CATARACT-SURGERY; FELLOW-EYES; FOLLOW-UP AB Background Glaucoma is one of the leading largely preventable causes of blindness in the world. It usually is addressed first medically with topical intraocular pressure-lowering drops or by laser trabeculoplasty. In cases where such treatment fails, glaucoma-filtering surgery is considered, most commonly trabeculectomy surgery with variations in technique, for example, the type of conjunctival flap (fornix-or limbal-based). In a fornix-based flap, the surgical wound is performed at the corneal limbus; while in a limbal-based flap, the incision is further away. Many studies in the literature compare fornix-and limbal-based trabeculectomy with respect to outcomes and complications. Objectives To assess the comparative effectiveness of fornix-versus limbal-based conjunctival flaps in trabeculectomy for adult glaucoma, with a specific focus on intraocular pressure (IOP) control and complications (adverse effects). Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to October 2015), EMBASE (January 1980 to October 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to October 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 23 October 2015. We reviewed the bibliographic references of identified randomised controlled trials (RCTs) in order to find trials not identified by the electronic searches. We contacted researchers and practitioners active in the field of glaucoma to identify other published and unpublished trials. Selection criteria We included RCTs comparing the benefits and complications of fornix-versus limbal-based trabeculectomy for glaucoma, irrespective of glaucoma type, publication status, and language. We excluded studies on children less than 18 years of age, since wound healing is different in this age group and the rate of bleb scarring postoperatively is high. Data collection and analysis Two review authors independently extracted data and assessed trial quality. We contacted study authors for additional information. The primary outcome was the proportion of failed trabeculectomies at 24 months. Failure was defined as the need for repeat surgery or uncontrolled IOP (more than 22 mmHg), despite additional topical/systemic medications. Needling and 5-fluorouracil (5-FU) injections were allowed only during the first six months postoperatively; additional needling or 5-FU injections were considered as failure. Mean post-operative IOP at 12 and 24 months also was recorded. Main results The review included six trials with a total of 361 participants. Two studies were conducted in America and one each in Germany, Greece, India, and Saudi Arabia. The participants of four trials had open-angle glaucoma; one study included participants with primary open-angle or primary closed-angle glaucoma, and one study did not specify the type of glaucoma. Three studies used a combined procedure (phacotrabeculectomy). Trabeculectomy with mitomycin C (MMC) was performed in four studies, and trabeculectomy with 5-fluorouracil (5-FU) was performed in only one study. None of the included trials reported trabeculectomy failure at 24 months. Only one trial reported the failure rate of trabeculectomy as a late complication. Failure was higher among participants randomised to the limbal-based surgery: 1/50 eyes failed trabeculectomy in the fornix group compared with 3/50 in the limbal group (risk ratio (RR) 0.33, 95% confidence interval (95% CI) 0.04 to 3.10); therefore we are very uncertain as to the relative effect of the two procedures on failure rate. Four studies including 252 participants provided measures of mean IOP at 12 months. In the fornix-based surgeries, mean IOP ranged from 12.5 to 15.5 mmHg and similar results were noted in limbal-based surgeries with mean IOP ranging from 11.7 to 15.1 mmHg without significant difference. Mean difference was 0.44 mmHg (95% CI -0.45 to 1.33) and 0.86 mmHg, (95% CI -0.52 to 2.24) at 12 and 24 months of follow-up, respectively. Neither of these pooled analyses showed a statistically significant difference in IOP between groups (moderate quality of evidence). One trial reported number of anti-glaucoma medications at 24 months of follow-up with no difference noted between surgical groups. However, three trials reported the mean number of anti-glaucoma medications at 12 months of follow-up without significant difference in the mean number of postoperative IOP-lowering medications between the two surgical techniques. Mean difference was 0.02, (95% CI -0.15 to 0.19) at 12 months of follow-up (high quality of evidence). Because of the small numbers of events and total participants, the risk of many reported adverse events were uncertain and those that were found to be statistically significant may have been due to chance. For risk of bias assessment: although all six trials were randomised selection bias was mostly unclear, with unclear random sequence generation in four of the six studies and unclear allocation concealment in five of the six studies. Attrition bias was encountered in only one trial which also suffered from reporting bias. All other trials had an unclear risk of reporting bias as there was no access to study protocols. All included trials were judged to have high risk of detection bias due to lack of masking of the outcomes. Trabeculectomy is quite a standard procedure and unlikely to induce bias due to surgeon 'performance', hence performance bias was not evaluated. Authors' conclusions The main result of this review was that there was uncertainty as to the difference between fornix-and limbal-based trabeculectomy surgeries due to the small number of events and confidence intervals that cross the null. This also applied to postoperative complications, but without any impact on long-term failure rate between the two surgical techniques. C1 [Al-Haddad, Christiane; Abdulaal, Marwan] Amer Univ Beirut, Med Ctr, Dept Ophthalmol, Beirut, Lebanon. [Al-Moujahed, Ahmad] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Ervin, Ann-Margret] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Al-Haddad, C (reprint author), Amer Univ Beirut, Med Ctr, Dept Ophthalmol, Hamrah St,POB 110236, Beirut, Lebanon. EM ca12@aub.edu.lb FU National Eye Institute, National Institutes of Health, USA; Cochrane Eyes and Vision - US Project [1 U01 EY020522]; National Institute for Research (NIHR), UK; Department of Health through the National Institute for Health Research; NIHR FX External sources; National Eye Institute, National Institutes of Health, USA.; Methodological support provided by Cochrane Eyes and Vision - US Project, funded by Grant 1 U01 EY020522.; National Institute for Research (NIHR), UK.; Richard Wormald, Co-ordinating Editor for Cochrane Eyes and Vision (CEV) acknowledges financial support for his CEV research sessions from the Department of Health through the award made by the National Institute for Health Research to Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology for a Specialist Biomedical Research Centre for Ophthalmology.; The NIHR also funds the CEV Editorial Base in London.; The views expressed in this publication are those of the authors and not necessarily those of the NIHR, NHS, or the Department of Health. NR 44 TC 1 Z9 1 U1 0 U2 1 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 2015 IS 11 AR CD009380 DI 10.1002/14651858.CD009380.pub2 PG 45 WC Medicine, General & Internal SC General & Internal Medicine GA CX9XQ UT WOS:000366060500035 PM 26599668 ER PT S AU Giosue, LB Luca, P AF Giosue, Lo Bosco Luca, Pinello BE DiSerio, C Lio, P Nonis, A Tagliaferri, R TI A New Feature Selection Methodology for K-mers Representation of DNA Sequences SO COMPUTATIONAL INTELLIGENCE METHODS FOR BIOINFORMATICS AND BIOSTATISTICS, CIBB 2014 SE Lecture Notes in Bioinformatics LA English DT Proceedings Paper CT 11th International Meeting on Computational Intelligence Methods for Bioinformatics and Biostatistics (CIBB) CY JUN 26-28, 2014 CL Cambridge, ENGLAND SP Bioinformat Italian Soc, Source Code Biol & Med, Univ Salerno, Dipartimento Informatica, Vita Salute San Raffaele Univ, Centro Univ Statistica Sci Biomediche, Univ Cambridge, Comp Lab, Int Neural Network Soc, Bioinformat & Intelligence SIG, IEEE CIS BBCT Task Forces Neural Networks & Evolutionary Computat DE k-mers; DNA sequence similarity; feature selection; DNA sequence classification ID NUCLEOSOME; PREDICTION; POSITIONS AB DNA sequence decomposition into k-mers and their frequency counting, defines a mapping of a sequence into a numerical space by a numerical feature vector of fixed length. This simple process allows to compare sequences in an alignment free way, using common similarities and distance functions on the numerical codomain of the mapping. The most common used decomposition uses all the substrings of a fixed length k making the codomain of exponential dimension. This obviously can affect the time complexity of the similarity computation, and in general of the machine learning algorithm used for the purpose of sequence analysis. Moreover, the presence of possible noisy features can also affect the classification accuracy. In this paper we propose a feature selection method able to select the most informative k-mers associated to a set of DNA sequences. Such selection is based on the Motif Independent Measure (MIM), an unbiased quantitative measure for DNA sequence specificity that we have recently introduced in the literature. Results computed on public datasets show the effectiveness of the proposed feature selection method. C1 [Giosue, Lo Bosco] Univ Palermo, Dipartimento Matemat & Informat, I-90133 Palermo, Italy. [Giosue, Lo Bosco] Ist Euro Mediterraneo Sci & Tecnol, Dipartimento Sci Innovaz & Tecnol Abilitanti, Palermo, Italy. [Luca, Pinello] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Luca, Pinello] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Giosue, LB (reprint author), Univ Palermo, Dipartimento Matemat & Informat, I-90133 Palermo, Italy. OI Lo Bosco, Giosue/0000-0002-1602-0693 NR 19 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 978-3-319-24462-4; 978-3-319-24461-7 J9 LECT N BIOINFORMAT JI Lect. Notes Bioinforma. PY 2015 VL 8623 BP 99 EP 108 DI 10.1007/978-3-319-24462-4_9 PG 10 WC Biochemical Research Methods; Computer Science, Artificial Intelligence; Computer Science, Information Systems; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Mathematical & Computational Biology GA BE0MG UT WOS:000366296700009 ER PT J AU Houde, AA Ruchat, SM Allard, C Baillargeon, JP St-Pierre, J Perron, P Gaudet, D Brisson, D Hivert, MF Bouchard, L AF Houde, Andree-Anne Ruchat, Stephanie-May Allard, Catherine Baillargeon, Jean-Patrice St-Pierre, Julie Perron, Patrice Gaudet, Daniel Brisson, Diane Hivert, Marie-France Bouchard, Luigi TI LRP1B, BRD2 and CACNA1D: new candidate genes in fetal metabolic programming of newborns exposed to maternal hyperglycemia SO EPIGENOMICS LA English DT Article DE cord blood; DNA methylation; epigenetics; gestational diabetes; placenta ID GESTATIONAL DIABETES-MELLITUS; DNA METHYLATION LEVELS; BETA-CELL FUNCTION; CORD BLOOD; PREGNANCY OUTCOMES; GLUCOSE-TOLERANCE; OBESITY; ASSOCIATION; LOCI; OVERWEIGHT AB Aim: To assess the associations between gestational diabetes mellitus (GDM) and DNA methylation levels at genes related to energy metabolism. Patients & methods: Ten loci were selected from our recent epigenome-wide association study on GDM. DNA methylation levels were quantified by bisulfite pyrosequencing in 80 placenta and cord blood samples (20 exposed to GDM) from an independent birth cohort (Gen3G). Results: We did not replicate association between DNA methylation and GDM. However, in normoglycemic women, glucose levels were associated with DNA methylation changes at LRP1B and BRD2 and at CACNA1D and LRP1B gene loci in placenta and cord blood, respectively. Conclusion: These results suggest that maternal glucose levels, within the normal range, are associated with DNA methylation changes at genes related to energy metabolism and previously associated with GDM. Maternal glycemia might thus be involved in fetal metabolic programming. C1 [Houde, Andree-Anne; Ruchat, Stephanie-May; Bouchard, Luigi] Univ Sherbrooke, Dept Biochem, Sherbrooke, PQ J1K 2R1, Canada. [Houde, Andree-Anne; Ruchat, Stephanie-May; St-Pierre, Julie; Perron, Patrice; Gaudet, Daniel; Brisson, Diane; Bouchard, Luigi] Chicoutimi Hosp, ECOGENE 21, Saguenay, PQ, Canada. [Houde, Andree-Anne; Ruchat, Stephanie-May; St-Pierre, Julie; Perron, Patrice; Gaudet, Daniel; Brisson, Diane; Bouchard, Luigi] Chicoutimi Hosp, Clin Res Ctr, Saguenay, PQ, Canada. [Houde, Andree-Anne; Ruchat, Stephanie-May; St-Pierre, Julie; Perron, Patrice; Gaudet, Daniel; Brisson, Diane; Bouchard, Luigi] Chicoutimi Hosp, Lipid Clin, Saguenay, PQ, Canada. [Allard, Catherine; Baillargeon, Jean-Patrice; Perron, Patrice; Hivert, Marie-France] Univ Sherbrooke, Dept Med, Div Endocrinol, Sherbrooke, PQ J1K 2R1, Canada. [St-Pierre, Julie] Chicoutimi Hosp, Dept Pediat, Saguenay, PQ, Canada. [St-Pierre, Julie] Univ Quebec Chicoutimi, Dept Hlth Sci, Saguenay, PQ, Canada. [Gaudet, Daniel; Brisson, Diane] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. [Hivert, Marie-France] Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA. [Hivert, Marie-France] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Bouchard, L (reprint author), Univ Sherbrooke, Dept Biochem, Sherbrooke, PQ J1K 2R1, Canada. EM luigi.bouchard@usherbrooke.ca FU ECOGENE- 21 Clinical Research Center; Canadian Institutes of Health Research (CIHR); Fonds de Recherche du Quebec en Sante (FRQS); Diabete Quebec; American Heart Association (AHA); American Diabetes Association (ADA); Fonds de la Recherche en Sante du Quebec (FRQS); Canadian Diabetes Association (CDA); Faculte de Medecine et des Sciences de la Sante de l'Universite de Sherbrooke FX This project was supported by ECOGENE-21 Clinical Research Center, the Canadian Institutes of Health Research (CIHR), the Fonds de Recherche du Quebec en Sante (FRQS) and Diabete Quebec. L Bouchard is a Junior Research Scholar from the Fonds de la Recherche en Sante du Quebec (FRQS). M-F Hivert was an FRSQ Research Scholar and was awarded Clinical Scientist award by the Canadian Diabetes Association (CDA); she is now supported by American Heart Association (AHA) and American Diabetes Association (ADA) awards. L Bouchard and M-F Hivert are members of the FRQS-funded Centre de recherche Clinique Etienne-Le Bel (affiliated with Centre Hospitalier Universitaire de Sherbrooke [CHUS]). A-A Houde is the recipient of doctoral training award from the FRQS and the Faculte de Medecine et des Sciences de la Sante de l'Universite de Sherbrooke. S-M Ruchat has received a postdoctoral fellowship from the CDA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 53 TC 2 Z9 2 U1 1 U2 6 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1750-1911 EI 1750-192X J9 EPIGENOMICS-UK JI Epigenomics PY 2015 VL 7 IS 7 BP 1111 EP 1122 DI 10.2217/epi.15.72 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA CY6XY UT WOS:000366553300006 PM 26586120 ER PT J AU Tsiachristas, A Waters, BH Adams, SA Bal, R Rutten-van Molken, MPMM AF Tsiachristas, A. Waters, B. Hipple Adams, S. A. Bal, R. Rutten-van Molken, M. P. M. M. TI Identifying and explaining the variability in development and implementation costs of disease management programs in the Netherlands SO INTERNATIONAL JOURNAL OF INTEGRATED CARE LA English DT Meeting Abstract DE chronic disease; disease management; integrated care; costs; the netherlands C1 [Tsiachristas, A.; Waters, B. Hipple; Adams, S. A.; Bal, R.; Rutten-van Molken, M. P. M. M.] Erasmus Univ, Inst Hlth Policy & Management, Rotterdam, Netherlands. [Tsiachristas, A.; Rutten-van Molken, M. P. M. M.] Erasmus Univ, Inst Med Technol Assessment, Rotterdam, Netherlands. [Waters, B. Hipple] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. EM apostolos.tsiachristas@dph.ox.ac.uk RI Rutten-van Molken, Maureen/G-8481-2014 OI Rutten-van Molken, Maureen/0000-0001-8706-3159 NR 0 TC 0 Z9 0 U1 0 U2 0 PU IGITUR, UTRECHT PUBLISHING & ARCHIVING SERVICES PI URTRECHT PA POSTBUS 80124, URTRECHT, 3508 TC, NETHERLANDS SN 1568-4156 J9 INT J INTEGR CARE JI Int. J. Integr. Care PY 2015 VL 15 SU S PG 2 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CY0HI UT WOS:000366086800124 ER PT J AU Fonda, JR Hunt, PR McGlinchey, RE Rudolph, JL Milberg, WP Reynolds, MW Yonan, C AF Fonda, Jennifer R. Hunt, Phillip R. McGlinchey, Regina E. Rudolph, James L. Milberg, William P. Reynolds, Matthew W. Yonan, Charles TI Identification of pseudobulbar affect symptoms in Veterans with possible traumatic brain injury SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE cross-sectional surveys; depression; emotional lability; lability scale; nervous system diseases; pseudobulbar affect; pseudobulbar syndromes; PTSD; traumatic brain injuries; Veterans ID IRAQ; AFGHANISTAN; DEPLOYMENT; MILITARY; ASSOCIATION; PERSONNEL; LABILITY; SCALE AB Pseudobulbar affect (PBA), a neurological syndrome characterized primarily by involuntary episodes of laughing and crying, can develop secondary to neurological conditions including traumatic brain injury (TBI). Veterans of the wars in Afghanistan and Iraq have an unprecedented risk for TBI, primarily from blast-related munitions. In this cross-sectional study with linkage to Department of Veterans Affairs (VA) clinical data, Veterans screening positive for TBI on the VA TBI screen (N = 4,282) were mailed packets containing two PBA symptom assessments: a single PBA symptom screen question and the Center for Neurologic Study-Lability Scale (CNS-LS) questionnaire. Seventy percent (n = 513) of the 728 Veteran respondents screened positive for PBA symptoms with a CNS-LS score of 13 or greater. There was strong concordance between PBA symptom prevalence measured with the single screening question and CNS-LS, with high sensitivity (0.87) and positive predictive value (0.93) and moderate specificity (0.79). Posttraumatic stress disorder (54% vs 32%), major depression (35% vs 22%), and anxiety disorder (20% vs 13%) were more common for Veterans with PBA symptoms than for those without. PBA symptoms were common in this Veteran cohort, were detected using simple screening tools, and often co-occurred with other psychiatric disorders common in Veterans. C1 [Fonda, Jennifer R.; McGlinchey, Regina E.; Rudolph, James L.; Milberg, William P.] Dept Vet Affairs Boston Healthcare Syst, Translat Res Ctr Traumat Brain Injury & Stress Di, Boston, MA USA. [Fonda, Jennifer R.; McGlinchey, Regina E.; Rudolph, James L.; Milberg, William P.] Dept Vet Affairs Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Fonda, Jennifer R.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Hunt, Phillip R.; Reynolds, Matthew W.] Evidera, Retrospect Observat Studies, Lexington, MA USA. [McGlinchey, Regina E.; Milberg, William P.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Rudolph, James L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Yonan, Charles] Avanir Pharmaceut Inc, Hlth Econ & Outcomes Res, Aliso Viejo, CA USA. RP Fonda, JR (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave, Boston, MA 02130 USA. EM jennifer.fonda@va.gov RI McGlinchey, Regina/R-1971-2016 FU Avanir Pharmaceuticals Inc.; VA Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence [B6796-C] FX This material was based on work supported by Avanir Pharmaceuticals Inc. Evidera provided support for the protocol and manuscript preparation, in collaboration with VA investigators. VA Boston Healthcare System and the Translational Research Center for TBI and Stress Disorders (TRACTS), which is a VA Rehabilitation Research and Development Traumatic Brain Injury Center of Excellence (grant B6796-C), are acknowledged for providing overall and infrastructural support. NR 27 TC 1 Z9 1 U1 6 U2 7 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 2015 VL 52 IS 7 BP 839 EP 849 DI 10.1682/JRRD.2014.08.0191 PG 11 WC Rehabilitation SC Rehabilitation GA CY3RG UT WOS:000366326700009 PM 26744849 ER PT S AU Aganj, I Iglesias, E Reuter, M Sabuncu, MR Fischl, B AF Aganj, Iman Iglesias, Eugenio Reuter, Martin Sabuncu, Mert R. Fischl, Bruce BE Navab, N Hornegger, J Wells, WM Frangi, AF TI Mid-Space-Independent Symmetric Data Term for Pairwise Deformable Image Registration SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2015, PT II SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 18th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) CY OCT 05-09, 2015 CL Munich, GERMANY SP Tech Univ Munich, Friedrich Alexander Univ Erlangen Nuremberg ID COMPUTATIONAL ANATOMY; NONRIGID REGISTRATION; BRAIN; ROBUST AB Aligning a pair of images in a mid-space is a common approach to ensuring that deformable image registration is symmetric - that it does not depend on the arbitrary ordering of the input images. The results are, however, generally dependent on the choice of the mid-space. In particular, the set of possible solutions is typically affected by the constraints that are enforced on the two transformations (that deform the two images), which are to prevent the mid-space from drifting too far from the native image spaces. The use of an implicit atlas has been proposed to define the mid-space for registration. In this work, by aligning the atlas to each image in the native image space, we make implicit-atlas-based pairwise registration independent of the mid-space, thereby eliminating the need for anti-drift constraints. We derive a new symmetric data term that only depends on a single transformation morphing one image to the other, and validate it through diffeomorphic registration experiments on brain MR images. C1 [Aganj, Iman; Reuter, Martin; Sabuncu, Mert R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr, Boston, MA 02138 USA. [Iglesias, Eugenio] Basque Ctr Cognit Brain & Language BCBL, San Sebastian, Spain. [Reuter, Martin; Sabuncu, Mert R.; Fischl, Bruce] MIT, CSAIL, Cambridge, MA 02139 USA. RP Aganj, I (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr, Boston, MA 02138 USA. EM iman@nmr.mgh.harvard.edu; e.iglesias@bcbl.eu; mreuter@nmr.mgh.harvard.edu; msabuncu@nmr.mgh.harvard.edu; fischl@nmr.mgh.harvard.edu NR 25 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0302-9743 BN 978-3-319-24571-3; 978-3-319-24570-6 J9 LECT NOTES COMPUT SC PY 2015 VL 9350 BP 263 EP 271 DI 10.1007/978-3-319-24571-3_32 PG 9 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging GA BE0KT UT WOS:000366206800032 ER PT S AU Le, M Delingette, H Kalpathy-Cramer, J Gerstner, ER Batchelor, T Unkelbach, J Ayache, N AF Le, Matthieu Delingette, Herve Kalpathy-Cramer, Jayashree Gerstner, Elizabeth R. Batchelor, Tracy Unkelbach, Jan Ayache, Nicholas BE Navab, N Hornegger, J Wells, WM Frangi, AF TI Bayesian Personalization of Brain Tumor Growth Model SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION - MICCAI 2015, PT II SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 18th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) CY OCT 05-09, 2015 CL Munich, GERMANY SP Tech Univ Munich, Friedrich Alexander Univ Erlangen Nuremberg ID UNCERTAINTY AB Recent work on brain tumor growth modeling for glioblastoma using reaction-diffusion equations suggests that the diffusion coefficient and the proliferation rate can be related to clinically relevant information. However, estimating these parameters is difficult due to the lack of identifiability of the parameters, the uncertainty in the tumor segmentations, and the model approximation, which cannot perfectly capture the dynamics of the tumor. Therefore, we propose a method for conducting the Bayesian personalization of the tumor growth model parameters. Our approach estimates the posterior probability of the parameters, and allows the analysis of the parameters correlations and uncertainty. Moreover, this method provides a way to compute the evidence of a model, which is a mathematically sound way of assessing the validity of different model hypotheses. Our approach is based on a highly parallelized implementation of the reaction-diffusion equation, and the Gaussian Process Hamiltonian Monte Carlo (GPHMC), a high acceptance rate Monte Carlo technique. We demonstrate our method on synthetic data, and four glioblastoma patients. This promising approach shows that the infiltration is better captured by the model compared to the speed of growth. C1 [Le, Matthieu; Delingette, Herve; Ayache, Nicholas] INRIA Sophia Antipolis, Asclepios Project, Nice, France. [Kalpathy-Cramer, Jayashree] Harvard Mit Div Hlth Sci & Technol, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Gerstner, Elizabeth R.; Batchelor, Tracy] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Unkelbach, Jan] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Le, M (reprint author), INRIA Sophia Antipolis, Asclepios Project, Nice, France. NR 12 TC 1 Z9 1 U1 0 U2 3 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0302-9743 BN 978-3-319-24571-3; 978-3-319-24570-6 J9 LECT NOTES COMPUT SC PY 2015 VL 9350 BP 424 EP 432 DI 10.1007/978-3-319-24571-3_51 PG 9 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging GA BE0KT UT WOS:000366206800051 ER PT J AU Gauna, AE Park, YJ Nayar, G Onate, M Jin, JO Stewart, CM Yu, Q Cha, S AF Gauna, Adrienne E. Park, Yun-Jong Nayar, Gautarn Onate, Marelys Jin, Jun-o Stewart, Carol M. Yu, Qing Cha, Seunghee TI Dysregulated co-stimulatory molecule expression in a Sjogren's syndrome mouse model with potential implications by microRNA-146a SO MOLECULAR IMMUNOLOGY LA English DT Article DE Sjogren's syndrome; microRNA; Co-stimulation; miR-146a; CD80; Salivary glands; Epithelial cells ID REGULATORY T-CELLS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; GLAND EPITHELIAL-CELLS; EMERGING ROLE; MIR-146A EXPRESSION; RESPONSES; CD80; CD28; INVOLVEMENT; ARTHRITIS AB Sjogren's syndrome (SjS) is an autoimmune condition that primarily affects salivary and lacrimal glands, causing loss of secretion. We have previously shown that microRNA-146a (miR-146a) is over-expressed in the salivary glands and peripheral blood mononuclear cells (PBMC) of SjS-prone mice (C57BL/6,NOD-Aec1Aec2, B6DC) and in PBMC of SjS patients. The purpose of this research was to identify a target molecule of miR-146a and identify subpopulations of cells affected by altered miR-146a in the salivary glands of SjS-prone mice. In silico analyses identified costimulatory molecule CD80 as a potential target of miR-146a. Luciferase assay of the human CD80 3'untranslated region demonstrated miR-146a directly inhibited CD80 protein expression as indicated by reduced luciferase reporter expression and an examination of B6DC salivary glands revealed a reduction in CD80 protein. More interestingly, the specific reduction in CD80 protein was detected from the salivary gland epithelial cell population and in interstitial dendritic cells in the glands as well. The reduction in CD80 protein levels in salivary gland epithelial cells were negatively associated with elevated miR-146a expression. Therefore, this study provides the first indication that salivary gland epithelial cells may be critically involved in SjS progression by altering CD86:CD80 protein ratio in response to miR-146a upregulation. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Gauna, Adrienne E.; Park, Yun-Jong; Nayar, Gautarn; Onate, Marelys; Stewart, Carol M.; Cha, Seunghee] Univ Florida, Dept Oral & Maxillofacial Diagnost Sci & Oral Bio, Coll Dent, Gainesville, FL 32610 USA. [Jin, Jun-o; Yu, Qing] Forsyth Inst, Dept Immunol & Infect Dis, Cambridge, MA 02142 USA. RP Cha, S (reprint author), Univ Florida, Dept Oral & Maxillofacial Diagnost Sci, Coll Dent, POB 100414, Gainesville, FL 32610 USA. EM agauna@dental.ufl.edu; yjpark@ufl.edu; gnayar33@gmail.com; Monate@dental.ufl.edu; Junojinl@gmail.com; cstewart@dental.ufl.edu; QYu@forsyth.org; scha@dental.ufl.edu FU National Institutes of Health (NIH)/National Institute of Dental and Craniofacial Research [DE019644, DE023838]; NIH/National Center for Advancing Translational Sciences, Clinical and Translational Sciences [UL1 TR000064/TL1 TR000066] FX This work was supported by grants from the National Institutes of Health (NIH)/National Institute of Dental and Craniofacial Research DE019644 (S.C.), DE023838 (QY.), and NIH/National Center for Advancing Translational Sciences, Clinical and Translational Sciences Awards UL1 TR000064/TL1 TR000066 (A.E.G.). Funding sources had no involvement in study design, collection, analysis or interpretation of data, writing of the report, or in the decision to submit the article for publication. NR 43 TC 0 Z9 1 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PY 2015 VL 68 IS 2 BP 606 EP 616 DI 10.1016/j.molimm.2015.09.027 PN C PG 11 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA CZ0AS UT WOS:000366768100015 PM 26505653 ER PT J AU Hatfield, SM Sitkovsky, M AF Hatfield, Stephen M. Sitkovsky, Michail TI Oxygenation to improve cancer vaccines, adoptive cell transfer and blockade of immunological negative regulators SO ONCOIMMUNOLOGY LA English DT Editorial Material DE Anti-tumor immunity; adenosine receptors; CD8+T cells; immunotherapies; oxygen; natural killer cells; tumor microenvironment; vaccine ID ADENOSINE; PROTECTION AB Oxygenation of tumors weakens the tumor-protecting immunosuppressive signaling by A2A adenosine receptors in hypoxic and extracellular adenosine-rich microenvironments. This, in turn, unleashes the otherwise inhibited tumor-reactive T and natural killer (NK) cells. Oxygenation of tumors thus emerges as a novel checkpoint inhibitor of potential therapeutic value, but only in combination with cancer immunotherapies. C1 [Hatfield, Stephen M.; Sitkovsky, Michail] Northeastern Univ, New England Inflammat & Tissue Protect Inst, Boston, MA 02115 USA. [Sitkovsky, Michail] Harvard Inst Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA USA. RP Sitkovsky, M (reprint author), Northeastern Univ, New England Inflammat & Tissue Protect Inst, Boston, MA 02115 USA. EM m.sitkovsky@neu.edu FU NCI NIH HHS [R01 CA111985] NR 9 TC 0 Z9 0 U1 3 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PY 2015 VL 4 IS 12 AR e1052934 DI 10.1080/2162402X.2015.1052934 PG 3 WC Oncology; Immunology SC Oncology; Immunology GA CY5AP UT WOS:000366420500019 PM 26587328 ER PT S AU Palmeri, M Nightingale, K Fielding, S Rouze, N Deng, YF Lynch, T Chen, SG Song, PF Urban, M Xie, H Wear, K Garra, B Milkowski, A Rosenzweig, S Carson, P Barr, R Shamdasani, V Macdonald, M Wang, M Guenette, G Miyajima, Y Okamura, Y Dhyani, M Samir, A Hah, Z McLaughlin, G Gee, A Chen, YL Napolitano, D McAleavey, S Obuchowski, N Hall, T AF Palmeri, Mark Nightingale, Kathy Fielding, Shana Rouze, Ned Deng, Yufeng Lynch, Ted Chen, Shigao Song, Pengfei Urban, Matthew Xie, Hua Wear, Keith Garra, Brian Milkowski, Andy Rosenzweig, Stephen Carson, Paul Barr, Richard Shamdasani, Vijay Macdonald, Michael Wang, Michael Guenette, Gilles Miyajima, Yasuo Okamura, Yoko Dhyani, Manish Samir, Anthony Hah, Zaegyoo McLaughlin, Glen Gee, Albert Chen, Yuling Napolitano, David McAleavey, Steve Obuchowski, Nancy Hall, Timothy GP IEEE TI RSNA QIBA Ultrasound Shear Wave Speed Phase II Phantom Study in Viscoelastic Media SO 2015 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IUS) SE IEEE International Ultrasonics Symposium LA English DT Proceedings Paper CT IEEE International Ultrasonics Symposium (IUS) CY OCT 21-24, 2015 CL Taipei, TAIWAN SP IEEE ID WFUMB GUIDELINES; CLINICAL-USE; LIVER; RECOMMENDATIONS; FIBROSIS AB Using ultrasonic shear wave speed (SWS) estimates has become popular to noninvasively evaluate liver fibrosis, but significant inter-system variability in liver SWS measurements can preclude meaningful comparison of measurements performed with different systems. The RSNA Quantitative Imaging Biomarker Alliance (QIBA) ultrasound SWS committee has been developing elastic and viscoelastic (VE) phantoms to evaluate system dependencies of SWS estimates. The objective of this study is to compare SWS measurements between commercially-available systems using phantoms that have viscoelastic properties similar to those observed in normal and fibrotic liver. CIRS, Inc. fabricated three phantoms using a proprietary oil-water emulsion infused in a Zerdine (R) hydrogel that were matched in viscoelastic behavior to healthy and fibrotic human liver data. Phantoms were measured at academic, clinical, government and vendor sites using different systems with curvilinear arrays at multiple focal depths (3.0, 4.5 & 7.0 cm). The results of this study show that current-generation ultrasound SWS measurement systems are able to differentiate viscoelastic materials that span healthy to fibrotic liver. The deepest focal depth (7.0 cm) yielded the greatest inter-system variability for each phantom (maximum of 17.7%) as evaluated by IQR. Inter-system variability was consistent across all 3 phantoms and was not a function of stiffness. Median SWS estimates for the greatest outlier system for each phantom/ focal depth combination ranged from 12.7-17.6%. Future efforts will include performing more robust statistical analyses of these data, comparing these phantom data trends with viscoelastic digital phantom data, providing vendors with study site data to refine their systems to have more consistent measurements, and integrating these data into the QIBA ultrasound shear wave speed measurement profile. C1 [Palmeri, Mark; Nightingale, Kathy; Fielding, Shana; Rouze, Ned; Deng, Yufeng] Duke Univ, Durham, NC 27708 USA. [Lynch, Ted] CIRS, Norfolk, VA USA. [Chen, Shigao; Song, Pengfei; Urban, Matthew] Mayo Clin, Rochester, MN USA. [Xie, Hua] Philips Res, Cambridge, MA USA. [Wear, Keith; Garra, Brian] US FDA, Rockville, MD 20857 USA. [Milkowski, Andy; Rosenzweig, Stephen] Siemens Ultrasound, Issaquah, WA USA. [Carson, Paul] Univ Michigan, Ann Arbor, MI 48109 USA. [Barr, Richard] Surg Hosp Southwoods, Boardman, OH USA. [Shamdasani, Vijay] Philips Ultrasound, Bothell, WA USA. [Macdonald, Michael; Wang, Michael] Gen Elect, Milwaukee, WI USA. [Guenette, Gilles; Miyajima, Yasuo; Okamura, Yoko] Toshiba Med Res Inst, Redmond, WA USA. [Dhyani, Manish; Samir, Anthony] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hah, Zaegyoo] Samsung Medison, Seoul, South Korea. [McLaughlin, Glen; Gee, Albert; Chen, Yuling; Napolitano, David] Zonare Med Syst, Mountain View, CA USA. [McAleavey, Steve] Univ Rochester, Rochester, NY USA. [Obuchowski, Nancy] Cleveland Clin, Cleveland, OH 44106 USA. [Hall, Timothy] Univ Wisconsin, Madison, WI USA. RP Palmeri, M (reprint author), Duke Univ, Durham, NC 27708 USA. NR 6 TC 0 Z9 0 U1 1 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1948-5719 BN 978-1-4799-8182-3 J9 IEEE INT ULTRA SYM PY 2015 DI 10.1109/ULTSYM.2015.0283 PG 4 WC Engineering, Electrical & Electronic SC Engineering GA BE0HK UT WOS:000366045700401 ER PT J AU Ciolino, JB McLaurin, EB Marsico, NP Ackerman, SL Williams, JM Villanueva, L Hollander, DA AF Ciolino, Joseph B. McLaurin, Eugene B. Marsico, Nicholas P. Ackerman, Stacey L. Williams, Julia M. Villanueva, Linda Hollander, David A. TI Effect of alcaftadine 0.25% on ocular itch associated with seasonal or perennial allergic conjunctivitis: a pooled analysis of two multicenter randomized clinical trials SO CLINICAL OPHTHALMOLOGY LA English DT Article DE lastacaft; seasonal allergen; perennial allergen; allergic rhinoconjunctivitis; conjunctival allergen challenge ID QUALITY-OF-LIFE; OLOPATADINE 0.2-PERCENT; HISTAMINE; SURFACE; ANTIHISTAMINES; INFLAMMATION; RECEPTORS AB Purpose: Seasonal and perennial allergic conjunctivitis represent the majority of cases of ocular allergy. This analysis was designed to evaluate the efficacy and safety of once-daily alcaftadine 0.25% in preventing ocular itching associated with seasonal or perennial allergic conjunctivitis. Subjects and methods: Pooled data from two double-masked, multicenter, placebo-controlled studies using the conjunctival allergen challenge (CAC) model of allergic conjunctivitis were analyzed. Subjects randomized to receive treatment with alcaftadine 0.25% or placebo were challenged with seasonal (grass, ragweed, trees) or perennial (cat dander, cat hair, dog dander, dust mites, cockroach) allergens, 16 hours after treatment instillation. The primary efficacy measure was subject-evaluated mean ocular itching at 3 minutes post-CAC. Secondary measures included ocular itching at 5 and 7 minutes post-CAC. The proportion of subjects with minimal itch (itch score. 1) and zero itch (itch score = 0), and safety were also assessed. Results: A total of 189 subjects enrolled in the two studies were treated with alcaftadine or placebo. Overall, 129 subjects were challenged with seasonal allergens and 60 subjects were challenged with perennial allergens. Alcaftadine 0.25% achieved a statistically significant reduction in mean itch score at 3, 5, and 7 minutes post-CAC compared with placebo in subjects challenged with seasonal allergens (P<0.0001 at all time points) and those challenged with perennial allergens (P<0.0001 at all time points). A higher percentage of subjects treated with alcaftadine compared with placebo achieved minimal itch (P<0.001 versus placebo at all time points) and zero itch (P<0.05 at all time points except 7 minutes for perennial) when challenged with either seasonal or perennial allergens. No treatment-related or serious adverse events were reported. Conclusion: Once-daily alcaftadine 0.25% ophthalmic solution was well tolerated and demonstrated effective relief of ocular itching in subjects challenged with allergens classic for triggering either seasonal or perennial allergic conjunctivitis. C1 [Ciolino, Joseph B.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [McLaurin, Eugene B.] Total Eye Care PA, Memphis, TN USA. [Marsico, Nicholas P.] East West Eye Inst, Los Angeles, CA USA. [Ackerman, Stacey L.] Philadelphia Eye Associates, Philadelphia, PA USA. [Williams, Julia M.; Villanueva, Linda; Hollander, David A.] Allergan Pharmaceut Inc, Irvine, CA USA. RP Ciolino, JB (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM joseph_ciolino@meei.harvard.edu NR 30 TC 1 Z9 1 U1 1 U2 2 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1177-5483 J9 CLIN OPHTHALMOL JI Clin. Ophthalmol. PY 2015 VL 9 BP 765 EP 772 DI 10.2147/OPTH.S80503 PG 8 WC Ophthalmology SC Ophthalmology GA CY3JD UT WOS:000366304500002 PM 25999684 ER PT J AU Lim, LS Ng, WY Mathur, R Wong, D Wong, EYM Yeo, I Cheung, CMG Lee, SY Wong, TY Papakostas, TD Kim, LA AF Lim, Laurence S. Ng, Wei Yan Mathur, Ranjana Wong, Doric Wong, Edmund Y. M. Yeo, Ian Cheung, Chui Ming Gemmy Lee, Shu Yen Wong, Tien Yin Papakostas, Thanos D. Kim, Leo A. TI Conversion to aflibercept for diabetic macular edema unresponsive to ranibizumab or bevacizumab SO CLINICAL OPHTHALMOLOGY LA English DT Article DE diabetic retinopathy; macular edema; aflibercept; bevacizumab; ranibizumab ID PLUS PROMPT LASER; VEGF TRAP-EYE; FOLLOW-UP; DEFERRED LASER; DA VINCI; SAFETY; RETINOPATHY; EFFICACY; THERAPY AB Background: The purpose of this study was to determine if eyes with diabetic macular edema (DME) unresponsive to ranibizumab or bevacizumab would benefit from conversion to aflibercept. Methods: This study was conducted as a retrospective chart review of subjects with DME unresponsive to ranibizumab and/or bevacizumab and subsequently converted to aflibercept. Results: In total, 21 eyes from 19 subjects of mean age 62 +/- 15 years were included. The majority of subjects were male (63%). The median number of ranibizumab or bevacizumab injections before switching to aflibercept was six, and the median number of aflibercept injections after switching was three. Median follow-up was 5 months after the switch. Mean central foveal thickness (CFT) was 453.52 +/- 143.39 mm immediately prior to the switch. Morphologically, intraretinal cysts were present in all cases. Mean CFT after the first injection decreased significantly to 362.57 +/- 92.82 mm (Wilcoxon signed-rank test; P<0.001). At the end of follow-up, the mean CFT was 324.17 +/- 98.76 mm (P<0.001). Mean visual acuity was 0.42 +/- 0.23 logMAR just prior to the switch, 0.39 +/- 0.31 logMAR after one aflibercept injection, and 0.37 +/- 0.22 logMAR at the end of follow-up. The final visual acuity was significantly better than visual acuity before the switch (P=0.04). Conclusion: Eyes with DME unresponsive to multiple ranibizumab/bevacizumab injections demonstrate anatomical and visual improvement on conversion to aflibercept. C1 [Lim, Laurence S.; Papakostas, Thanos D.; Kim, Leo A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv, Boston, MA USA. [Lim, Laurence S.; Ng, Wei Yan; Mathur, Ranjana; Wong, Doric; Wong, Edmund Y. M.; Yeo, Ian; Cheung, Chui Ming Gemmy; Lee, Shu Yen; Wong, Tien Yin] Singapore Natl Eye Ctr, Vitreoretinal Dept, Singapore 168751, Singapore. RP Lim, LS (reprint author), Singapore Natl Eye Ctr, Vitreoretinal Dept, 11 Third Hosp Ave, Singapore 168751, Singapore. EM llimshen@gmail.com NR 19 TC 9 Z9 10 U1 0 U2 1 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1177-5483 J9 CLIN OPHTHALMOL JI Clin. Ophthalmol. PY 2015 VL 9 BP 1715 EP 1718 DI 10.2147/OPTH.S81523 PG 4 WC Ophthalmology SC Ophthalmology GA CY4GK UT WOS:000366366400001 PM 26396494 ER PT J AU Minzenberg, MJ Lesh, T Niendam, T Yoon, JH Cheng, YA Rhoades, RN Carter, CS AF Minzenberg, Michael J. Lesh, Tyler Niendam, Tara Yoon, Jong H. Cheng, Yaoan Rhoades, Remy N. Carter, Cameron S. TI Frontal Motor Cortex Activity During Reactive Control Is Associated With Past Suicidal Behavior in Recent-Onset Schizophrenia SO CRISIS-THE JOURNAL OF CRISIS INTERVENTION AND SUICIDE PREVENTION LA English DT Article DE suicide; schizophrenia; fMRI; cognitive control; prefrontal cortex ID DORSOLATERAL PREFRONTAL CORTEX; POSITRON-EMISSION-TOMOGRAPHY; 1ST EPISODE PSYCHOSIS; COGNITIVE-CONTROL; NEURAL MECHANISMS; CEREBRAL-CORTEX; PREMOTOR AREAS; BRAIN ACTIVITY; DYSFUNCTION; CONFLICT AB Background: Suicide is prevalent in schizophrenia (SZ), yet the neural system functions that confer suicide risk remain obscure. Circuits operated by the prefrontal cortex (PFC) are altered in SZ, including those that support reactive control, and PFC changes are observed in postmortem studies of heterogeneous suicide victims. Aims: We tested whether history of suicide attempt is associated with altered frontal motor cortex activity during reactive control processes. Method: We evaluated 17 patients with recent onset of DSM-IV-TR-defined SZ using the Columbia Suicide Severity Rating Scale and functional magnetic resonance imaging during Stroop task performance. Group-level regression models relating pas suicidal behavior to frontal activation controlled for depression, psychosis, and impulsivity. Results: Past suicidal behavior was associated with relatively higher activation in the left-hemisphere supplementary motor area (SMA), pre-SMA, premotor cortex, and dorsolateral PFC, all ipsilateral to the active primary motor cortex. Conclusion: This study provides unique evidence that suicidal behavior in patients with recent-onset SZ directly relates to frontal motor cortex activity during reactive control, in a pattern reciprocal to the relationship with proactive control found previously. Further work should address how frontal-based control functions change with risk over time, and their potential utility as a biomarker for interventions to mitigate suicide risk in SZ. C1 [Minzenberg, Michael J.; Cheng, Yaoan] Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA. [Lesh, Tyler; Niendam, Tara; Carter, Cameron S.] Univ Calif Davis, Sch Med, Dept Psychiat, Sacramento, CA 95817 USA. [Carter, Cameron S.] Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA. [Yoon, Jong H.; Rhoades, Remy N.] Stanford Sch Med, Dept Psychiat, Palo Alto, CA USA. RP Minzenberg, MJ (reprint author), San Francisco VA Med Ctr, Outpatient Mental Hlth, 116C,4150 Clement St, San Francisco, CA 94121 USA. EM michael.minzenberg@ucsf.edu FU American Foundation for Suicide Prevention; Doris Duke Charitable Foundation [2009045]; [MH059883] FX This work was supported by an American Foundation for Suicide Prevention Young Investigator Award and the Doris Duke Charitable Foundation Grant # 2009045, both to MJM, and MH059883 to CSC. The authors have no disclosures to declare. NR 54 TC 1 Z9 1 U1 1 U2 7 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA MERKELSTR 3, D-37085 GOTTINGEN, GERMANY SN 0227-5910 EI 2151-2396 J9 CRISIS JI Crisis PY 2015 VL 36 IS 5 BP 363 EP 370 DI 10.1027/0227-5910/a000335 PG 8 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA CY2EI UT WOS:000366221200009 PM 26502787 ER PT J AU Kayman, DJ Goldstein, MF Dixon, L Goodman, M AF Kayman, Deborah J. Goldstein, Marjorie F. Dixon, Lisa Goodman, Marianne TI Perspectives of Suicidal Veterans on Safety Planning Findings From a Pilot Study SO CRISIS-THE JOURNAL OF CRISIS INTERVENTION AND SUICIDE PREVENTION LA English DT Article DE suicide; prevention; safety plan; veterans; mobile mental health ID RANDOMIZED CONTROLLED-TRIAL; EMERGENCY-DEPARTMENT; BRIEF INTERVENTION; COGNITIVE THERAPY; SELF-HARM; FOLLOW-UP; RISK; PREVENTION; MILITARY; RATIONALE AB Aims: Individual interviews were conducted and analyzed to learn about the engagement of suicidal veterans in safety planning. Method: Twenty suicidal veterans who had recently constructed safety plans were recruited at two VA hospitals. In semistructured interviews, they discussed how they felt about constructing and using the plan and suggested changes in plan content and format that might increase engagement. Results: The veterans' experiences varied widely, from reviewing plans often and noting symptom improvement to not using them at all and doubting that they would think of doing so when deeply depressed. Conclusion: The veterans suggested ways to enrich safety planning encounters and identified barriers to plan use. Their ideas were specific and practical. Safety planning was most meaningful and helpful to them when they experienced the clinician as a partner in exploring their concerns (e.g., fear of discussing and attending to warning signs) and collaborating with them to devise solutions. C1 [Kayman, Deborah J.; Dixon, Lisa; Goodman, Marianne] James J Peters Med Ctr, Dept Vet Affairs, Bronx, NY 10468 USA. [Goldstein, Marjorie F.] Natl Dev & Res Inst Inc NDRI, New York, NY USA. [Dixon, Lisa] Columbia Univ, Med Ctr, New York, NY USA. [Dixon, Lisa] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Goodman, Marianne] Mt Sinai Hosp, Icahn Sch Med, New York, NY 10029 USA. RP Kayman, DJ (reprint author), James J Peters Med Ctr, Dept Vet Affairs, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM deborah.kayman@va.gov FU Department of Defense [W81XWH-09-1-0722]; Medical Research Service of the Department of Veterans Affairs, James J. Peters Medical Center; Department of Veterans Affairs, Veterans Integrated Service Network 3, Mental Illness Research Education and Clinical Center (MIRECC) FX This work was supported by the Department of Defense #W81XWH-09-1-0722 (M. Goodman, Principal Investigator), the Medical Research Service of the Department of Veterans Affairs, James J. Peters Medical Center, and the Department of Veterans Affairs, Veterans Integrated Service Network 3, Mental Illness Research Education and Clinical Center (MIRECC). NR 35 TC 0 Z9 0 U1 1 U2 7 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA MERKELSTR 3, D-37085 GOTTINGEN, GERMANY SN 0227-5910 EI 2151-2396 J9 CRISIS JI Crisis PY 2015 VL 36 IS 5 BP 371 EP 383 DI 10.1027/0227-5910/a000348 PG 13 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA CY2EI UT WOS:000366221200010 PM 26502788 ER PT J AU Tritos, NA AF Tritos, Nicholas A. TI Is there a role for targeted medical therapies in patients with craniopharyngiomas? SO FUTURE ONCOLOGY LA English DT Editorial Material DE adamantinomatous craniopharyngioma; BRAF; dabrafenib; papillary craniopharyngioma; vemurafenib ID BETA-CATENIN; MUTATIONS; SURVIVAL; MELANOMA; VEMURAFENIB; MORBIDITY; GENE C1 [Tritos, Nicholas A.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. RP Tritos, NA (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM ntritos@mgh.harvard.edu NR 17 TC 0 Z9 0 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 EI 1744-8301 J9 FUTURE ONCOL JI Future Oncol. PY 2015 VL 11 IS 24 BP 3221 EP 3223 DI 10.2217/fon.15.233 PG 3 WC Oncology SC Oncology GA CY1PW UT WOS:000366180700001 PM 26562628 ER PT J AU Waks, AG Tolaney, SM AF Waks, Adrienne G. Tolaney, Sara M. TI The evolving understanding of small HER2-positive breast cancers: matching management to outcomes SO FUTURE ONCOLOGY LA English DT Review DE APT trial; ATEMPT trial; breast cancer; HER2; stage I; T1abN0; trastuzumab; trastuzumab-emtansine ID ESTROGEN-RECEPTOR STATUS; TRASTUZUMAB EMTANSINE; ADJUVANT CHEMOTHERAPY; OPEN-LABEL; DOCETAXEL; WOMEN; PLUS; AMPLIFICATION; PACLITAXEL; SURVIVAL AB Systemic therapy for small (stage I) HER2-positive breast cancers has long posed a dilemma for clinicians, as the majority of these patients were excluded from the large adjuvant trastuzumab trials. However in the decade since those trials were reported, data have accumulated to suggest that recurrence risk for these small but biologically aggressive tumors is nontrivial. In this review, we summarize data from numerous cohort studies describing the outcomes of small HER2-positive tumors, mostly in the absence of HER2-directed therapy. We then examine the potential impact of HER2-directed treatment in this population, culminating in the recently published prospective study of paclitaxel/trastuzumab therapy. The landscape of next generation anti-HER2 therapies is quickly evolving; a role for some of these agents in the small HER2-positive subpopulation may also be on the horizon. C1 [Waks, Adrienne G.; Tolaney, Sara M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Waks, AG (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM awaks@partners.org; Sara_Tolaney@dfci.harvard.edu FU Genentech FX SM Tolaney receives research funding from Genentech. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 37 TC 0 Z9 0 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 EI 1744-8301 J9 FUTURE ONCOL JI Future Oncol. PY 2015 VL 11 IS 24 BP 3261 EP 3271 DI 10.2217/fon.15.240 PG 11 WC Oncology SC Oncology GA CY1PW UT WOS:000366180700007 PM 26634944 ER PT S AU Schleef, M Schirmbeck, R Reiser, M Michel, ML Schmeer, M AF Schleef, Martin Schirmbeck, R. Reiser, Michael Michel, Marie-Louise Schmeer, Marco BE Walther, W Stein, U TI Minicircle : Next Generation DNA Vectors for Vaccination SO GENE THERAPY OF SOLID CANCERS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE DNA immunization; HBV vaccine; Hepatitis B virus; Minicircle; Mini-plasmid ID HYDRODYNAMICS-BASED TRANSFECTION; SITE-SPECIFIC RECOMBINATION; VOLUME JET-INJECTION; DIRECT GENE-TRANSFER; B SURFACE-ANTIGEN; IN-VIVO; PLASMID DNA; TRANSGENE EXPRESSION; ANTIBODY-RESPONSES; IMMUNE-RESPONSES AB The use of DNA vaccines requires pharmaceutical grade DNA that causes the immunization on the basis of a nucleic acid sequence that encodes the protein to be vaccinated against. This nucleic acid sequence can be a circular or linear plasmid, preferably a double stranded one and should not contain any other and especially not any "toxic" sequences. Sequences that are not desirable to be part of the DNA drug can be those deriving from the (typically) bacterial amplification system to produce the DNA vaccine. These could be those portions of a plasmid that are only used for controlling the bacterial replication of the plasmid or those used to select for the plasmid during cloning or even worse during production. After initial approaches to avoid the presence of these sequences in DNA vaccine plasmids with "mini-plasmids," a significant improvement in product safety was obtained by use of minicircles-circular and ccc-supercoiled expression cassettes of the DNA vaccine. Initial results proofed their extremely high expression level and recent comparison of DNA vaccines based on either plasmid or minicircle DNA show successful vaccination against HBV in mice, as shown in this overview chapter. C1 [Schleef, Martin; Schmeer, Marco] PlasmidFactory GmbH & Co KG, Bielefeld, Germany. [Schirmbeck, R.; Reiser, Michael] Univ Hosp Ulm, Dept Internal Med 1, Ulm, Germany. [Reiser, Michael] Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Charlestown, MA USA. [Michel, Marie-Louise] Inst Pasteur, Dept Virol, Paris, France. RP Schleef, M (reprint author), PlasmidFactory GmbH & Co KG, Bielefeld, Germany. NR 65 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-2727-2; 978-1-4939-2726-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1317 BP 327 EP 339 DI 10.1007/978-1-4939-2727-2_18 D2 10.1007/978-1-4939-2727-2 PG 13 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA BE0GK UT WOS:000365990100019 PM 26072415 ER PT S AU Smith, DJ AF Smith, D. J. BE Watson, RR DeMeester, F TI Passive immunoglobulin Y immunotherapy targeting oral diseases SO HANDBOOK OF EGGS IN HUMAN FUNCTION SE Human Health Handbooks LA English DT Article; Book Chapter DE dental caries; periodontal disease; Gtf; adhesin; GbpB; gingipain; Streptococcus mutans; Porphoromonas gingivalis; Fusobacterium nucleatum ID CELL-ASSOCIATED GLUCOSYLTRANSFERASE; BINDING-PROTEIN-B; EGG-YOLK ANTIBODY; STREPTOCOCCUS-MUTANS; DENTAL-CARIES; MONOCLONAL-ANTIBODIES; GLUCAN-BINDING; PORPHYROMONAS-GINGIVALIS; PROTECTIVE IMMUNITY; PERIODONTAL-DISEASE AB Dental caries and periodontal disease have a bacterial component in their etiology. Chicken egg yolk immunoglobulin Y (IgY) antibodies directed Streptococcus mutans, Porphoromonas gingivalis or Fusobacterium nucleatum have been investigated for their ability to intercept or modulate the infectious component of these diseases. IgY antibody was prepared to S. mutans adhesins, glucosyltransferase (Gtf) or glucan binding protein B, components associated with adhesion or accumulation of S. mutans. Dietary administration of these IgY reagents in experimental rodent models for dental caries has shown reductions in dental caries, even when IgY was added to the diet only in the first phase of infection. In short-term clinical trial delivery of lozenges containing IgY antibody to cell-associated Gtf was associated with reduced colonization of potentially cariogenic S. mutans. IgY antibody was also prepared to whole cells or virulence components of two putative periodontal pathogens, P. gingivalis and F. nucleatum. IgY antibody to P. gingivalis hemagglutinin A or outer membrane protein interfered with hemagglutinating activity of P. gingivalis vesicles or coaggregation of P. gingivalis with S. gordonii, respectively. Two clinical trials using IgY antibody to P. gingivalis gingipains suggested that direct application of this antibody to the periodontal pocket or periodic oral administration in tablets could improve periodontal health and reduce numbers of P. gingivalis. Passive antibody therapy might also be useful in humans in whom the anti-bacterial properties of their saliva has been compromised by autoimmune or radiation-induced ablation of salivary flow. Challenges for use of IgY as an immunotherapeutic for these oral diseases are the timing of application, appropriate delivery vehicle and likelihood that more than one microorganism may contribute to the pathogenic effects observed. C1 [Smith, D. J.] Forsyth Inst, Dept Immunol, Cambridge, MA 02142 USA. [Smith, D. J.] Harvard Univ, Sch Med, Sch Dent Med, Dept Infect Immun & Oral Med, Boston, MA 02115 USA. RP Smith, DJ (reprint author), Forsyth Inst, Dept Immunol, 145 First St, Cambridge, MA 02142 USA. EM dsmith@forsyth.org NR 40 TC 0 Z9 0 U1 1 U2 1 PU WAGENINGEN ACAD PUBL PI WAGENINGEN PA POSTBUS 220, 6700 AE WAGENINGEN, NETHERLANDS SN 2212-375X BN 978-90-8686-804-9; 978-90-8686-254-2 J9 HUM HEALT HANDB PY 2015 IS 9 BP 429 EP 445 DI 10.3920/978-90-8686-804-9_24 D2 10.3920/978-90-8686-804-9 PG 17 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA BE0DR UT WOS:000365865400025 ER PT J AU Mahadevan, A Dagoglu, N Mancias, J Raven, K Khwaja, K Tseng, JF Ng, K Enzinger, P Miksad, R Bullock, A Evenson, A AF Mahadevan, Anand Dagoglu, Nergiz Mancias, Joseph Raven, Kristin Khwaja, Khalid Tseng, Jennifer F. Kimmie Ng Enzinger, Peter Miksad, Rebecca Bullock, Andrea Evenson, Amy TI Stereotactic Body Radiotherapy (SBRT) for Intrahepatic and Hilar Cholangiocarcinoma SO JOURNAL OF CANCER LA English DT Article DE stereotactic body radiotherapy; cholangiocarcinomas ID BILE-DUCT CARCINOMA; BILIARY-TRACT CANCERS; PHASE I/II TRIAL; RADIATION-THERAPY; LIVER-TRANSPLANTATION; EXTRAHEPATIC CHOLANGIOCARCINOMA; PERIHILAR CHOLANGIOCARCINOMA; POSTOPERATIVE RADIOTHERAPY; IR-192 BRACHYTHERAPY; EXTERNAL-BEAM AB Background: Unresectable intrahepatic and hilar cholangiocarcinomas carry a dismal prognosis. Systemic chemotherapy and conventional external beam radiation and brachytherapy have been used with limited success. We explored the use of stereotactic body radiotherapy (SBRT) for these patients. Methods: Patients with unresectable intrahepatic or hilar cholangiocarcinoma or those with positive margins were included in this study. Systemic therapy was used at the discretion of the medical oncologist. The Cyberknife (TM) stereotactic body radiotherapy system used to treat these patients. Patients were treated with three daily fractions. Clinical and radiological follow-up were performed every three months. Results: 34 patients (16 male and 18 female) with 42 lesions were included in this study. There were 32 unresectable tumors and two patients with resected tumors with positive margins. The median SBRT dose was 30Gy in three fractions. The median follow-up was 38 months (range 8-71 months). The actuarial local control rate was 79%. The median overall survival was 17 months and the median progression free survival was ten months. There were four Grade III toxicities (12%), including duodenal ulceration, cholangitis and liver abscess. Conclusions: SBRT is an effective and reasonably safe local therapy option for unresectable intrahepatic or hilar cholangiocarcinoma. C1 [Mahadevan, Anand; Dagoglu, Nergiz; Mancias, Joseph] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. [Raven, Kristin; Khwaja, Khalid; Tseng, Jennifer F.; Evenson, Amy] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Kimmie Ng; Enzinger, Peter] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Miksad, Rebecca; Bullock, Andrea] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02115 USA. RP Evenson, A (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, 330 Brookline Ave, Boston, MA 02215 USA. EM amahadev@bidmc.harvard.edu FU NCI NIH HHS [P50 CA127003] NR 52 TC 4 Z9 6 U1 1 U2 2 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2015 VL 6 IS 11 BP 1099 EP 1104 DI 10.7150/jca.13032 PG 6 WC Oncology SC Oncology GA CY3AS UT WOS:000366280800005 PM 26516357 ER PT J AU Bianchi, MT AF Bianchi, Matt T. TI Consumer Sleep Apps: When it Comes to the Big Picture, it's All About the Frame SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Editorial Material ID CIRCADIAN-RHYTHMS; ACTIGRAPHY C1 [Bianchi, Matt T.] Massachusetts Gen Hosp, Dept Neurol, Sleep Div, Boston, MA 02114 USA. RP Bianchi, MT (reprint author), Massachusetts Gen Hosp, Wang Neurol 7, 55 Fruit St, Boston, MA 02114 USA. EM mtbianchi@partners.org NR 10 TC 2 Z9 2 U1 2 U2 4 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 2015 VL 11 IS 7 BP 695 EP 696 DI 10.5664/jcsm.4834 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA CY3CP UT WOS:000366286100001 PM 26094923 ER PT J AU Auger, RR Burgess, HJ Emens, JS Deriy, LV Sharkey, KM AF Auger, R. Robert Burgess, Helen J. Emens, Jonathan S. Deriy, Ludmila V. Sharkey, Katherine M. TI Do Evidence-Based Treatments for Circadian Rhythm Sleep-Wake Disorders Make the GRADE? Updated Guidelines Point to Need for More Clinical Research SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Editorial Material ID PHASE SYNDROME; MELATONIN C1 [Auger, R. Robert] Mayo Ctr Sleep Med, Rochester, MN 55905 USA. [Burgess, Helen J.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Emens, Jonathan S.] Portland VA Med Ctr, Portland, OR USA. [Deriy, Ludmila V.] Amer Acad Sleep Med, Darien, IL USA. [Sharkey, Katherine M.] Brown Univ, Providence, RI 02912 USA. RP Auger, RR (reprint author), Mayo Ctr Sleep Med, Rochester, MN 55905 USA. EM research@aasmnet.org NR 12 TC 1 Z9 1 U1 0 U2 0 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 2015 VL 11 IS 10 BP 1079 EP 1080 AR PII jc-00354-15 DI 10.5664/jcsm.5072 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA CY3FO UT WOS:000366294100002 PM 26414984 ER PT J AU Casey, KR Teodorescu, M AF Casey, Kenneth R. Teodorescu, Mihai TI Postoperative Complications in Patients with Obstructive Sleep Apnea: Where Do We Stand? SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Editorial Material ID POSITIVE AIRWAY PRESSURE; CONTROLLED-TRIAL; OUTCOMES; SURGERY; METAANALYSIS; COHORT; IMPACT C1 [Casey, Kenneth R.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. Wisconsin Sleep, Madison, WI USA. Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA. RP Casey, KR (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace, Madison, WI 53705 USA. EM krcasey@msn.com NR 10 TC 1 Z9 1 U1 0 U2 0 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 2015 VL 11 IS 10 BP 1081 EP 1082 AR PII jc-00396-15 DI 10.5664/jcsm.5074 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA CY3FO UT WOS:000366294100003 PM 26414991 ER PT J AU Auger, RR Burgess, HJ Emens, JS Deriy, LV Thomas, SM Sharkey, KM AF Auger, R. Robert Burgess, Helen J. Emens, Jonathan S. Deriy, Ludmila V. Thomas, Sherene M. Sharkey, Katherine M. TI Clinical Practice Guideline for the Treatment of Intrinsic Circadian Rhythm Sleep-Wake Disorders: Advanced Sleep-Wake Phase Disorder (ASWPD), Delayed Sleep-Wake Phase Disorder (DSWPD), Non-24-Hour Sleep-Wake Rhythm Disorder (N24SWD), and Irregular Sleep-Wake Rhythm Disorder (ISWRD). An Update for 2015 SO JOURNAL OF CLINICAL SLEEP MEDICINE LA English DT Article DE circadian rhythms; DSWPD; ASWPD; N24SWD; ISWRD ID BRIGHT-LIGHT TREATMENT; PLACEBO-CONTROLLED TRIAL; NURSING-HOME RESIDENTS; RUNNING BLIND PEOPLE; ENRICHED POLYCHROMATIC-LIGHT; CONTROLLED-RELEASE MELATONIN; RANDOMIZED CONTROLLED-TRIAL; REST-ACTIVITY DISRUPTION; SHORT-WAVELENGTH LIGHT; ALZHEIMERS-DISEASE AB A systematic literature review and meta-analyses (where appropriate) were performed and the GRADE approach was used to update the previous American Academy of Sleep Medicine Practice Parameters on the treatment of intrinsic circadian rhythm sleep-wake disorders. Available data allowed for positive endorsement (at a second-tier degree of confidence) of strategically timed melatonin (for the treatment of DSWPD, blind adults with N24SWD, and children/adolescents with ISWRD and comorbid neurological disorders), and light therapy with or without accompanying behavioral interventions (adults with ASWPD, children/adolescents with DSWPD, and elderly with dementia). Recommendations against the use of melatonin and discrete sleep-promoting medications are provided for demented elderly patients, at a second-and first-tier degree of confidence, respectively. No recommendations were provided for remaining treatments/populations, due to either insufficient or absent data. Areas where further research is needed are discussed. C1 [Auger, R. Robert] Mayo Ctr Sleep Med, Rochester, MN 55905 USA. [Burgess, Helen J.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Emens, Jonathan S.] Portland VA Med Ctr, Portland, OR USA. [Deriy, Ludmila V.; Thomas, Sherene M.] Amer Acad Sleep Med, Darien, IL USA. [Sharkey, Katherine M.] Brown Univ, Providence, RI 02912 USA. RP Auger, RR (reprint author), Mayo Ctr Sleep Med, Rochester, MN 55905 USA. EM research@aasmnet.org FU American Academy of Sleep Medicine FX The authors acknowledge Dr. Ilene Rosen for serving as a board liaison for this project and assuring that the guideline adhered to the standards set forth by the Board of Directors of American Academy of Sleep Medicine. The authors also acknowledge the contributions of the following individuals: Christine Stepanski, MS, for performing literature searches #1 and #2; and Michelle M. Tangredi, PhD, for managing the project at the initial steps. The authors are grateful to the organizations and individuals who provided their insights and suggestions during the public comment period. Every comment was internally documented and addressed, and decisions regarding corresponding amendments in the text were left to the TF's discretion. The project was funded by the American Academy of Sleep Medicine. NR 198 TC 17 Z9 17 U1 11 U2 20 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 2015 VL 11 IS 10 BP 1199 EP 1236 AR PII jc-00358-15 DI 10.5664/jcsm.5100 PG 38 WC Clinical Neurology SC Neurosciences & Neurology GA CY3FO UT WOS:000366294100016 PM 26414986 ER PT J AU Tapias, LF Lanuti, M AF Tapias, Luis F. Lanuti, Michael TI Solitary fibrous tumors of the pleura: review of literature with up-to-date observations SO LUNG CANCER MANAGEMENT LA English DT Review DE malignant pleural tumor; pleural tumor; solitary fibrous tumor ID SURGICAL-TREATMENT; CLINICOPATHOLOGICAL FEATURES; LOCALIZED BENIGN; SCORING SYSTEM; MESOTHELIOMA; RECURRENCE; VALIDATION; VARIANTS; FUSION; SERIES AB Solitary fibrous tumors of the pleura (SFTP) are rare mesenchymal tumors with unpredictable biologic characteristics. Attempts have been made to standardize prognostic criteria without improvement in predicting prognosis or recurrence. The infrequent nature of this tumor contributes to the paucity of data that are used to make useful observations. Here, we present a comprehensive review of contemporary literature to summarize important clinical management aspects of patients with SFTP, focusing on surgical treatment, the role for adjuvant therapies, the potential impact of new prognostic models and the management of recurrences. SFTP remains poorly understood; therefore, new information such as a detailed molecular characterization may improve current prognostic models and lead to new treatment strategies. C1 [Tapias, Luis F.; Lanuti, Michael] Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02114 USA. [Tapias, Luis F.; Lanuti, Michael] Harvard Univ, Sch Med, Boston, MA USA. RP Lanuti, M (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02114 USA. EM mlanuti@mgh.harvard.edu NR 37 TC 1 Z9 1 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1758-1966 EI 1758-1974 J9 LUNG CANCER MANAG JI Lung Cancer Manag. PY 2015 VL 4 IS 4 BP 169 EP 179 DI 10.2217/LMT.15.19 PG 11 WC Respiratory System SC Respiratory System GA CX9RW UT WOS:000366044000004 ER PT S AU Le, M Unkelbach, J Ayache, N Delingette, H AF Le, Matthieu Unkelbach, Jan Ayache, Nicholas Delingette, Herve BE Navab, N Hornegger, J Wells, WM Frangi, AF TI GPSSI: Gaussian Process for Sampling Segmentations of Images SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION, PT III SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 18th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) CY OCT 05-09, 2015 CL Munich, GERMANY SP Tech Univ Munich, Friedrich Alexander Univ Erlangen Nuremberg AB Medical image segmentation is often a prerequisite for clinical applications. As an ill-posed problem, it leads to uncertain estimations of the region of interest which may have a significant impact on downstream applications, such as therapy planning. To quantify the uncertainty related to image segmentations, a classical approach is to measure the effect of using various plausible segmentations. In this paper, a method for producing such image segmentation samples from a single expert segmentation is introduced. A probability distribution of image segmentation boundaries is defined as a Gaussian process, which leads to segmentations that are spatially coherent and consistent with the presence of salient borders in the image. The proposed approach outperforms previous generative segmentation approaches, and segmentation samples can be generated efficiently. The sample variability is governed by a parameter which is correlated with a simple DICE score. We show how this approach can have multiple useful applications in the field of uncertainty quantification, and an illustration is provided in radiotherapy planning. C1 [Le, Matthieu; Ayache, Nicholas; Delingette, Herve] INRIA Sophia Antipolis, Asclepios Project, Valbonne, France. [Unkelbach, Jan] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Unkelbach, Jan] Harvard Univ, Sch Med, Boston, MA USA. RP Le, M (reprint author), INRIA Sophia Antipolis, Asclepios Project, Valbonne, France. NR 10 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0302-9743 BN 978-3-319-24574-4; 978-3-319-24573-7 J9 LECT NOTES COMPUT SC PY 2015 VL 9351 BP 38 EP 46 DI 10.1007/978-3-319-24574-4_5 PG 9 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging GA BE0FR UT WOS:000365963800005 ER PT S AU Sabuncu, MR AF Sabuncu, Mert R. BE Navab, N Hornegger, J Wells, WM Frangi, AF TI A Sparse Bayesian Learning Algorithm for Longitudinal Image Data SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION, PT III SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 18th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) CY OCT 05-09, 2015 CL Munich, GERMANY SP Tech Univ Munich, Friedrich Alexander Univ Erlangen Nuremberg DE Machine learning; Image-based prediction; Longitudinal data ID CLASSIFICATION AB Longitudinal imaging studies, where serial (multiple) scans are collected on each individual, are becoming increasingly widespread. The field of machine learning has in general neglected the longitudinal design, since many algorithms are built on the assumption that each datapoint is an independent sample. Thus, the application of general purpose machine learning tools to longitudinal image data can be sub-optimal. Here, we present a novel machine learning algorithm designed to handle longitudinal image datasets. Our approach builds on a sparse Bayesian image-based prediction algorithm. Our empirical results demonstrate that the proposed method can offer a significant boost in prediction performance with longitudinal clinical data. C1 [Sabuncu, Mert R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02138 USA. RP Sabuncu, MR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02138 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0302-9743 BN 978-3-319-24574-4; 978-3-319-24573-7 J9 LECT NOTES COMPUT SC PY 2015 VL 9351 BP 411 EP 418 DI 10.1007/978-3-319-24574-4_49 PG 8 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging GA BE0FR UT WOS:000365963800049 ER PT S AU Annunziata, R Kheirkhah, A Hamrah, P Trucco, E AF Annunziata, Roberto Kheirkhah, Ahmad Hamrah, Pedram Trucco, Emanuele BE Navab, N Hornegger, J Wells, WM Frangi, AF TI Scale and Curvature Invariant Ridge Detector for Tortuous and Fragmented Structures SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION, PT III SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 18th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) CY OCT 05-09, 2015 CL Munich, GERMANY SP Tech Univ Munich, Friedrich Alexander Univ Erlangen Nuremberg AB Segmenting dendritic trees and corneal nerve fibres is challenging due to their uneven and irregular appearance in the respective image modalities. State-of-the-art approaches use hand-crafted features based on local assumptions that are often violated by tortuous and point-like structures, e.g., straight tubular shape. We propose a novel ridge detector, SCIRD, which is simultaneously rotation, scale and curvature invariant, and relaxes shape assumptions to achieve enhancement of target image structures. Experimental results on three datasets show that our approach outperforms state-of-the-art hand-crafted methods on tortuous and point-like structures, especially when captured at low resolution or limited signal-to-noise ratio and in the presence of other non-target structures. C1 [Annunziata, Roberto; Trucco, Emanuele] Univ Dundee, Sch Comp, Dundee, Scotland. [Kheirkhah, Ahmad; Hamrah, Pedram] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Annunziata, R (reprint author), Univ Dundee, Sch Comp, Dundee, Scotland. EM r.annunziata@dundee.ac.uk NR 13 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0302-9743 BN 978-3-319-24574-4; 978-3-319-24573-7 J9 LECT NOTES COMPUT SC PY 2015 VL 9351 BP 588 EP 595 DI 10.1007/978-3-319-24574-4_70 PG 8 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging GA BE0FR UT WOS:000365963800070 ER PT S AU Annunziata, R Kheirkhah, A Hamrah, P Trucco, E AF Annunziata, Roberto Kheirkhah, Ahmad Hamrah, Pedram Trucco, Emanuele BE Navab, N Hornegger, J Wells, WM Frangi, AF TI Boosting Hand-Crafted Features for Curvilinear Structure Segmentation by Learning Context Filters SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION, PT III SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 18th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) CY OCT 05-09, 2015 CL Munich, GERMANY SP Tech Univ Munich, Friedrich Alexander Univ Erlangen Nuremberg ID ORIENTED FLUX AB Combining hand-crafted features and learned filters (i.e. feature boosting) for curvilinear structure segmentation has been proposed recently to capture key structure configurations while limiting the number of learned filters. Here, we present a novel combination method pairing hand-crafted appearance features with learned context filters. Unlike recent solutions based only on appearance filters, our method introduces context information in the filter learning process. Moreover, it reduces the potential redundancy of learned appearance filters that may be reconstructed using a combination of hand-crafted filters. Finally, the use of k-means for filter learning makes it fast and easily adaptable to other datasets, even when large dictionary sizes (e.g. 200 filters) are needed to improve performance. Comprehensive experimental results using 3 challenging datasets show that our combination method outperforms recent state-of-the-art HCFs and a recent combination approach for both performance and computational time. C1 [Annunziata, Roberto; Trucco, Emanuele] Univ Dundee, Sch Comp, Dundee, Scotland. [Kheirkhah, Ahmad; Hamrah, Pedram] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Annunziata, R (reprint author), Univ Dundee, Sch Comp, Dundee, Scotland. NR 15 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 0302-9743 BN 978-3-319-24574-4; 978-3-319-24573-7 J9 LECT NOTES COMPUT SC PY 2015 VL 9351 BP 596 EP 603 DI 10.1007/978-3-319-24574-4_71 PG 8 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging GA BE0FR UT WOS:000365963800071 ER PT J AU Divita, G Carter, M Redd, A Zeng, Q Gupta, K Trautner, B Samore, M Gundlapalli, A AF Divita, G. Carter, M. Redd, A. Zeng, Q. Gupta, K. Trautner, B. Samore, M. Gundlapalli, A. TI Scaling-up NLP Pipelines to Process Large Corpora of Clinical Notes SO METHODS OF INFORMATION IN MEDICINE LA English DT Article DE Natural language processing; big data; scale-up ID TEXT AB Introduction: This article is part of the Focus Theme of Methods of Information in Medicine on "Big Data and Analytics in Healthcare". Objectives: This paper describes the scale-up efforts at the VA Salt Lake City Health Care System to address processing large corpora of clinical notes through a natural language processing (NLP) pipeline. The use case described is a current project focused on detecting the presence of an indwelling urinary catheter in hospitalized patients and subsequent catheter-associated urinary tract infections. Methods: An NLP algorithm using v3NLP was developed to detect the presence of an indwelling urinary catheter in hospitalized patients. The algorithm was tested on a small corpus of notes on patients for whom the presence or absence of a catheter was already known (reference standard). In planning for a scale-up, we estimated that the original algorithm would have taken 2.4 days to run on a larger corpus of notes for this project (550,000 notes), and 27 days for a corpus of 6 million records representative of a national sample of notes. We approached scaling-up NLP pipelines through three techniques: pipeline replication via multi-threading, intra-annotator threading for tasks that can be further decomposed, and remote annotator services which enable annotator scale-out. Results: The scale-up resulted in reducing the average time to process a record from 206 milliseconds to 17 milliseconds or a 12-fold increase in performance when applied to a corpus of 550,000 notes. Conclusions: Purposely simplistic in nature, these scale-up efforts are the straight forward evolution from small scale NLP processing to larger scale extraction without in curring associated complexities that are inherited by the use of the underlying UIMA framework. These efforts represent generalizable and widely applicable techniques that will aid other computationally complex NLP pipelines that are of need to be scaled out for processing and analyzing big data. C1 [Divita, G.; Carter, M.; Redd, A.; Zeng, Q.; Samore, M.; Gundlapalli, A.] VA Salt Lake City Hlth Care Syst, Salt Lake City, UT USA. [Divita, G.; Carter, M.; Redd, A.; Zeng, Q.; Samore, M.; Gundlapalli, A.] Univ Utah, Sch Med, Salt Lake City, UT 84132 USA. [Gupta, K.] VA Boston Healthcare Syst, Boston, MA USA. [Gupta, K.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Trautner, B.] VA Houston Hlth Care Syst, Houston, TX USA. [Trautner, B.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Divita, G (reprint author), Univ Utah, Sch Med, Div Epidemiol, 295 Chipeta Way, Salt Lake City, UT 84132 USA. EM guy.divita@hsc.utah.edu FU VA HSRD [CRE12-315, RRP 12-443] FX Resources were provided by the VA Salt Lake City Health Care System (IDEAS Center). We acknowledge our colleagues at VINCI for their assistance with accessing VA 'big data'. A portion of the software was developed under grant CRE12-315 (PI: Zeng) and RRP 12-443 from VA HSR&D (PI: Trautner). The views expressed in this paper are those of the authors and do not necessarily represent the views of the U.S. Department of Veterans Affairs or the United States Government. V3NLP is distributed under an [Apache] Open Source licensing agreement and is available for download at v3nlp.utah.edu. NR 16 TC 3 Z9 3 U1 2 U2 7 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PY 2015 VL 54 IS 6 BP 548 EP 552 DI 10.3414/ME14-02-0018 PG 5 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA CX9RR UT WOS:000366043500011 PM 26534722 ER PT S AU Karajannis, MA Stemmer-Rachamimov, A AF Karajannis, Matthias A. Stemmer-Rachamimov, Anat BE Karajannis, MA Zagzag, D TI Schwannomas SO MOLECULAR PATHOLOGY OF NERVOUS SYSTEM TUMORS: BIOLOGICAL STRATIFICATION AND TARGETED THERAPIES SE Molecular Pathology Library LA English DT Article; Book Chapter ID NF2 TUMOR-SUPPRESSOR; COMPARATIVE GENOMIC HYBRIDIZATION; PROGRESSIVE VESTIBULAR SCHWANNOMAS; PSAMMOMATOUS MELANOTIC SCHWANNOMA; KNIFE STEREOTACTIC RADIOSURGERY; NEUROFIBROMATOSIS TYPE-2 NF2; GROWTH-FACTOR; CELLULAR SCHWANNOMA; CARNEY COMPLEX; MOLECULAR CHARACTERIZATION C1 [Karajannis, Matthias A.] NYU, Pediat & Otolaryngol, Langone Med Ctr, New York, NY 10016 USA. [Stemmer-Rachamimov, Anat] Harvard Univ, Sch Med, Dept Pathol, Div Neuropathol,Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Karajannis, MA (reprint author), NYU, Pediat & Otolaryngol, Langone Med Ctr, New York, NY 10016 USA. NR 102 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1935-987X BN 978-1-4939-1830-0; 978-1-4939-1829-4 J9 MOL PATHOL LIB PY 2015 BP 201 EP 211 DI 10.1007/978-1-4939-1830-0_15 D2 10.1007/978-1-4939-1830-0 PG 11 WC Oncology; Pathology SC Oncology; Pathology GA BD7CW UT WOS:000362896300017 ER PT J AU Soni, A Aspinall, SL Zhao, XH Good, CB Cunningham, FE Chatta, G Passero, V Smith, KJ AF Soni, Amy Aspinall, Sherrie L. Zhao, Xinhua Good, Chester B. Cunningham, Francesca E. Chatta, Gurkamal Passero, Vida Smith, Kenneth J. TI Cost-Effectiveness Analysis of Adjuvant Stage III Colon Cancer Treatment at Veterans Affairs Medical Centers SO ONCOLOGY RESEARCH LA English DT Article DE Colon cancer; 5-Fluorouracil (5-FU); Capecitabine; Oxaliplatin; Cost-effectiveness ID X-ACT TRIAL; COLORECTAL-CANCER; NSABP C-07; OXALIPLATIN; CAPECITABINE; FLUOROURACIL; LEUCOVORIN; SURVIVAL; CHEMOTHERAPY; 5-FLUOROURACIL/LEUCOVORIN AB The objective of this study was to evaluate the real-world cost effectiveness of adjuvant stage III colon cancer chemotherapy regimens, given that previous analyses have been based on data from clinical trials. The study was designed using integrated decision tree and Markov model, which was developed to evaluate the cost effectiveness of 5-fluorouracil/leucovorin (5-FU/LV), capecitabine, and the combination of each with oxaliplatin. The analysis was performed from a US Veterans Affairs perspective via retrospectively collected data, over a 5-year model time horizon. Outcome and cost data were used to calculate cost per quality adjusted life year (QALY), and one-way and probabilistic sensitivity analyses were performed. In the base case analysis, capecitabine and capecitabine plus oxaliplatin both cost more and were less effective than other regimens, and 5-FU/LV plus oxaliplatin, compared to 5-FU/LV alone, resulted in a cost of $25,997 per QALY gained. Model results were generally robust to parameter variation. Capecitabine plus oxaliplatin could be economically reasonable if full dosing occurred 3 76% of the time (base case 42%). In a real-world setting, the addition of oxaliplatin to 5-FU/LV is more effective but also more costly than 5-FU/LV alone. If full dosing of capecitabine-containing regimens can be assured, they may also be cost-effective strategies. C1 [Soni, Amy] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Aspinall, Sherrie L.; Good, Chester B.; Cunningham, Francesca E.] VA Pharm Benefits Management Serv, Hines, IL USA. [Aspinall, Sherrie L.; Zhao, Xinhua; Good, Chester B.] VA Pittsburgh Healthcare Syst, VA Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Aspinall, Sherrie L.; Good, Chester B.] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA USA. [Good, Chester B.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Chatta, Gurkamal] Virginia Mason Med Ctr, Seattle, WA 98101 USA. [Passero, Vida] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Smith, Kenneth J.] Univ Pittsburgh, Div Clin Modeling & Decis Sci, Pittsburgh, PA USA. RP Soni, A (reprint author), Palo Alto Med Fdn, Sunnyvale Ctr, 301 Old San Francisco Rd,Level 1, Sunnyvale, CA 94086 USA. EM soniac@sutterhealth.org FU VA Pharmacy Benefits Management Services, Hines, IL, USA; VA Pittsburgh Healthcare System, Pittsburgh, PA, USA; VA medical centers FX The views expressed in this article are those of the authors, and no official endorsement by the Department of Veteran Affairs or the United States Government is intended or should be inferred. There was no funding support for the work. These findings are the result of work supported in kind by VA Pharmacy Benefits Management Services, Hines, IL, USA, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA, and the other VA medical centers that participated in the study. None of the authors has a relevant financial interest in this manuscript. The VA Oncology Pharmacotherapy Research Group includes Bernadette B. Heron, Pharm.D. (VA Pharmacy Benefits Management Services, Hines, IL, USA); Mark Geraci, Pharm.D. (VA Pharmacy Benefits Management Services, Hines, IL, USA); Roslyn A. Stone, Ph.D. (VA Pittsburgh Healthcare System, Pittsburgh, PA, USA; University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA); Renee Rogers, Pharm.D. (VA Pittsburgh Healthcare System, Pittsburgh, PA, USA); Jenna Shields, Pharm.D. (VA Pittsburgh Healthcare System, Pittsburgh, PA, USA); Megan Sartore, Pharm.D. (VA Pittsburgh Healthcare System, Pittsburgh, PA, USA); D. Patrick Boyle, RPh (VA Maine Health Care System, Augusta, ME, USA); Sherry Giberti, CTR (VA Maine Health Care System, Augusta, ME, USA); John Szymanski, Pharm.D. (VA Connecticut Healthcare System, West Haven, CT, USA); Doug Smith, Pharm.D. (Martinsburg VA Medical Center, Martinsburg, WV, USA); Allen Ha, Pharm.D. (Richmond VA Medical Center, Richmond, VA, USA); Jolynn Sessions, Pharm.D. (Asheville VA Medical Center, Asheville, NC, USA); Shawn Depcinski, Pharm.D. (James A. Haley Veterans Hospital, Tampa, FL, USA); Shane Fishco, Pharm.D. (James A. Haley Veterans Hospital, Tampa, FL, USA); Irvin Molina, Pharm.D. (Miami VA Medical Center, Miami, FL, USA); Tanja Lepir, Pharm.D. (Miami VA Medical Center, Miami, FL, USA); Carmela Jean, Pharm.D. (Miami VA Medical Center, Miami, FL, USA); Lymaris Cruz-Diaz, Pharm.D. (VA Caribbean Healthcare System, San Juan, PR, USA); Jessica Motta, Pharm.D. (VA Caribbean Healthcare System, San Juan, PR, USA); Rebeca Calderon-Vargas, Pharm.D. (VA Caribbean Healthcare System, San Juan, PR, USA); Janelle Maland, Pharm.D. (Harry S. Truman VA Hospital, Columbia, MO, USA); Sean Keefe, Pharm.D. (Kansas City VA Medical Center, Kansas City, MO, USA); Marshall Tague, Pharm.D. (Iowa City VA Medical Center, Iowa City, IA, USA); Alice Leone, R. Ph. (Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA); Brian Glovack, Pharm.D. (Jesse Brown VA Medical Center, Chicago, IL, USA); Blair Kaplan, Pharm.D. (Jesse Brown VA Medical Center, Chicago, IL, USA); Sean Cosgriff, Pharm.D. (Portland VA Medical Center, Portland, OR, USA); Lindsay Kaster, Pharm.D. (Boise VA Medical Center, Boise, ID, USA); Ivy Tonnu-Mihara, Pharm.D. Long Beach VA Medical Center, Long Beach, CA, USA); Kimmai Nguyen, Pharm.D. (Long Beach VA Medical Center, Long Beach, CA, USA); Jenna Carmichael, Pharm.D. (VA Sierra Nevada Health Care System, Reno, NV, USA); and Kan Lu, Pharm.D. (Sacramento VA Medical Center, Mather, CA, USA). NR 31 TC 0 Z9 0 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0965-0407 EI 1555-3906 J9 ONCOL RES JI Oncol. Res. PY 2015 VL 22 IS 5-6 BP 311 EP 319 DI 10.3727/096504015X14424348426152 PG 9 WC Oncology SC Oncology GA CY1UB UT WOS:000366192300009 ER PT J AU Schackman, BR Haas, DW Park, SS Li, XC Freedberg, KA AF Schackman, Bruce R. Haas, David W. Park, Sanghee S. Li, X. Cynthia Freedberg, Kenneth A. TI Cost-effectiveness of CYP2B6 genotyping to optimize efavirenz dosing in HIV clinical practice SO PHARMACOGENOMICS LA English DT Article DE antiretroviral therapy; cost-effectiveness; dose optimization; genotyping; HIV ID INITIAL ANTIRETROVIRAL THERAPY; INFECTED PATIENTS; PLASMA-CONCENTRATIONS; DOUBLE-BLIND; DOSE REDUCTION; UNITED-STATES; TRIALS; INDIVIDUALS; REGIMENS; PHARMACOKINETICS AB To assess the cost-effectiveness of CYP2B6 genotyping to guide efavirenz dosing for initial HIV therapy in the USA. Methods: We used the Cost-Effectiveness of Preventing AIDS Complications (CEPAC) microsimulation model to project quality-adjusted life expectancy and lifetime costs (2014 US dollars) for efavirenz-based HIV therapy with or without CYP2B6 genotyping. We assumed that with genotyping 60% of patients would be eligible to receive lower doses. Results: Current care without CYP2B6 genotyping has an incremental cost-effectiveness ratio >$100,000/QALY compared with genotype-guided dosing, even if lower dosing reduces efficacy. When we assumed generic efavirenz availability, conclusions were similar unless lower dosing reduces efficacy by 6% or more. Conclusion: CYP2B6 genotyping can inform efavirenz dosing and decrease HIV therapy cost. C1 [Schackman, Bruce R.] Weill Cornell Med Coll, Dept Healthcare Policy & Res, New York, NY 10065 USA. [Haas, David W.] Vanderbilt Univ, Sch Med, Dept Med, Div Infect Dis, Nashville, TN 37212 USA. [Park, Sanghee S.; Li, X. Cynthia; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Div Gen Internal Med, Boston, MA 02114 USA. [Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Freedberg, Kenneth A.] Harvard TH Chan Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. RP Schackman, BR (reprint author), Weill Cornell Med Coll, Dept Healthcare Policy & Res, New York, NY 10065 USA. EM brs2006@med.cornell.edu; kfreedberg@partners.org FU National Institute of Allergy and Infectious Diseases [R37AI42006, R01 AI077505, AI069439, AI110527]; National Center for Advancing Translational Sciences [TR000445] FX This work was supported by the National Institute of Allergy and Infectious Diseases (R37AI42006 to BR Schackman, SS Park, XC Li, KA Freedberg, R01 AI077505 to BR Schackman, DW Haas, SS Park, XC Li, KA Freedberg, and AI069439 and AI110527 to DW Haas) and the National Center for Advancing Translational Sciences (TR000445 to DW Haas). DW Haas has been a consultant to Merck. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 51 TC 7 Z9 7 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 EI 1744-8042 J9 PHARMACOGENOMICS JI Pharmacogenomics PY 2015 VL 16 IS 18 BP 2007 EP 2018 DI 10.2217/pgs.15.142 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CX9RP UT WOS:000366043300002 PM 26607811 ER PT J AU Omara, W Amin, R Elhaes, H Ibrahim, M Elfeky, SA AF Omara, Wessam Amin, Rehab Elhaes, Hanan Ibrahim, Medhat Elfeky, Souad A. TI Preparation and Characterization of Novel Polyaniline Nanosensor for Sensitive Detection of Formaldehyde SO RECENT PATENTS ON NANOTECHNOLOGY LA English DT Article DE EB-PANI; Formaldehyde; HF/3-21G**; molecular modeling; polyaniline nanosensor ID NANOFIBERS AB Nanomaterials are promising in the field of optical sensors due to their unique properties. Emeraldine base of polyaniline (Nano EB-PANI) was prepared, characterized and applied as an optical formaldehyde sensor. FTIR data confirm the formation of the EB-PANI. TEM and SEM revealed the size and shape of the nanoscale EB-PANI. XRD showed that the obtained nano EB-PANI has a partial crystalline nature. The sensing mechanism is based on the reaction of formaldehyde with Nano EB-PANI- to form a complex as described by molecular modeling HF/3-21G** level of theory. Results showed that Nano EB-PANI- detect low concentrations of formaldehyde ranging from 0.0003 to 0.9 ppm in a dose-dependent manner. The molecular modeling theory analysis showed that formaldehyde could interact with the amine of EB-PANI in, ring 3 or 4 or both together. The binding energy and dipole moment of the interaction between formaldehyde and polyaniline nanosensor were calculated by HF/3-21g** level of theory. The interaction with ring 3-NH gives a less stable product with a high dipole moment 6.978 Debye comparing with 1.678 Debye for the product of formaldehyde interaction with the terminal ring 4-NH. The development of such novel EB-PANI nanosensor can be used as, reliable and sensitive formaldehyde sensor. C1 [Omara, Wessam; Amin, Rehab; Elfeky, Souad A.] Cairo Univ, Laser Applicat Metrol Photochem & Agr, Natl Inst Laser Enhanced Sci, Giza, Egypt. [Amin, Rehab] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Elhaes, Hanan] Ain Shams Univ, Fac Women Arts Sci & Educ, Phys Dept, Cairo 11757, Egypt. [Ibrahim, Medhat] Natl Res Ctr, Spect Dept, Giza 12311, Egypt. [Elfeky, Souad A.] Univ Bath, Dept Chem, Bath BA2 7AY, Avon, England. RP Ibrahim, M (reprint author), Cairo Univ, Laser Applicat Metrol Photochem & Agr, Natl Inst Laser Enhanced Sci, Giza, Egypt. EM rehabamin@niles.edu.eg; dr_souad_elfeky@niles.edu.eg FU National Institute of Laser Enhanced Science, Cairo University FX This work was sponsored by National Institute of Laser Enhanced Science, Cairo University. NR 37 TC 0 Z9 0 U1 3 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1872-2105 EI 2212-4020 J9 RECENT PAT NANOTECH JI Recent Pat. Nanotechnology PY 2015 VL 9 IS 3 BP 195 EP 203 DI 10.2174/1872210510999151126112509 PG 9 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Science & Technology - Other Topics; Materials Science; Physics GA CY1VX UT WOS:000366197200003 PM 27009134 ER PT S AU Chen, YB Yuan, KY McDonald, J AF Chen, Yabing Yuan, Kaiyu McDonald, Jay BE Bonavida, B Chouaib, S TI Pancreatic Cancer Resistance to TRAIL Therapy: Regulators of the Death Inducing Signaling Complex SO RESISTANCE OF CANCER CELLS TO CTL-MEDIATED IMMUNOTHERAPY SE Resistance to Targeted Anti-Cancer Therapeutics LA English DT Article; Book Chapter DE Pancreatic cancer; TRAIL; Resistance; Apoptosis; Death receptor; Death-inducing signaling complex ID TUMOR-NECROSIS-FACTOR; HISTONE DEACETYLASE INHIBITORS; AGONISTIC MONOCLONAL-ANTIBODY; RECEPTOR-MEDIATED APOPTOSIS; LIGAND-INDUCED APOPTOSIS; X-LINKED INHIBITOR; CELL LUNG-CANCER; METASTATIC COLORECTAL-CANCER; ADVANCED SOLID MALIGNANCIES; SMALL-MOLECULE ANTAGONISTS AB Pancreatic cancer is the fourth leading cause of cancer deaths in the United States. It is generally a fatal cancer with poor prognosis. Once pancreatic cancer becomes metastatic, it is uniformly fatal with an overall average survival of typically 6 months. The only potentially curative therapy for pancreatic cancer is surgical resection. Unfortunately, the majority of pancreatic cancer patients have advanced and inoperable disease at the time of diagnosis. Studies from our group and others have supported that modulating tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis provides potential novel avenues for cancer therapy. However, resistance of pancreatic cancer to TRAIL therapy remains a large clinical hurdle. Thus, better understanding of the molecular events regulating pancreatic cancer cell apoptosis would facilitate the development of novel strategies to enhance the efficacy of TRAIL therapy. Dysregulation of apoptosis of tumor cells plays an important role in the pancreatic cancer pathogenesis and their resistance to therapies. We and others have demonstrated that the formation of death receptor-activated death-inducing signaling complex (DISC) and the recruitment of DISC components determine both the downstream apoptotic and survival signaling pathways. We have identified several components in the death receptor-activated DISC that mediate death receptor-induced survival pathways, including FLIP and three new DISC components, calmodulin (CaM), Src and poly(ADP-ribose) polymerase (PARP-1), which contribute to the resistance of cancer cells to death receptor-activated apoptosis. This review discusses the roles of TRAIL death receptors and the molecular regulators in the DISC that contribute to the resistance to TRAIL-induced apoptosis. The specific apoptotic regulators as potential therapeutic targets for TRAIL-resistant pancreatic cancers are emphasized, including death receptor 5 (DR5), FLIP, CaM, Src and PARP-1. C1 [Chen, Yabing; Yuan, Kaiyu; McDonald, Jay] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Chen, Yabing; McDonald, Jay] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. RP Chen, YB (reprint author), Univ Alabama Birmingham, Dept Pathol, 614 Shelby Biomed Res Bldg,1825 Univ Blvd, Birmingham, AL 35294 USA. EM ybchen@uab.edu NR 226 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 2196-5501 BN 978-3-319-17807-3; 978-3-319-17806-6 J9 RESIST TARGET ANTI-C PY 2015 VL 7 BP 235 EP 265 DI 10.1007/978-3-319-17807-3_11 D2 10.1007/978-3-319-17807-3 PG 31 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA BE0FJ UT WOS:000365951300012 ER PT J AU Bernacki, R Hutchings, M Vick, J Smith, G Paladino, J Lipsitz, S Gawande, AA Block, SD AF Bernacki, Rachelle Hutchings, Mathilde Vick, Judith Smith, Grant Paladino, Joanna Lipsitz, Stuart Gawande, Atul A. Block, Susan D. TI Development of the Serious Illness Care Program: a randomised controlled trial of a palliative care communication intervention SO BMJ OPEN LA English DT Article ID OF-LIFE CARE; FACULTY-DEVELOPMENT PROGRAM; CELL LUNG-CANCER; PATIENTS PREFERENCES; SURPRISE QUESTION; TERMINAL ILLNESS; CLINICAL-TRIALS; END; DEATH; SCALE AB Introduction Ensuring that patients receive care that is consistent with their goals and values is a critical component of high-quality care. This article describes the protocol for a cluster randomised controlled trial of a multicomponent, structured communication intervention. Methods and analysis Patients with advanced, incurable cancer and life expectancy of <12months will participate together with their surrogate. Clinicians are enrolled and randomised either to usual care or the intervention. The Serious Illness Care Program is a multicomponent, structured communication intervention designed to identify patients, train clinicians to use a structured guide for advanced care planning discussion with patients, trigger' clinicians to have conversations, prepare patients and families for the conversation, and document outcomes of the discussion in a structured format in the electronic medical record. Clinician satisfaction with the intervention, confidence and attitudes will be assessed before and after the intervention. Self-report data will be collected from patients and surrogates approximately every 2months up to 2years or until the patient's death; patient medical records will be examined at the close of the study. Analyses will examine the impact of the intervention on the patient receipt of goal-concordant care, and peacefulness at the end of life. Secondary outcomes include patient anxiety, depression, quality of life, therapeutic alliance, quality of communication, and quality of dying and death. Key process measures include frequency, timing and quality of documented conversations. Ethics and dissemination This study was approved by the Dana-Farber Cancer Institute Institutional Review Board. Results will be reported in peer-reviewed publications and conference presentations. Trial registration number Protocol identifier NCT01786811; Pre-results. C1 [Bernacki, Rachelle; Gawande, Atul A.; Block, Susan D.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Bernacki, Rachelle; Hutchings, Mathilde; Paladino, Joanna; Block, Susan D.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Bernacki, Rachelle; Hutchings, Mathilde; Paladino, Joanna; Lipsitz, Stuart; Gawande, Atul A.; Block, Susan D.] Brigham & Womens Hosp, Ariadne Labs, Boston, MA 02115 USA. [Bernacki, Rachelle; Hutchings, Mathilde; Paladino, Joanna; Lipsitz, Stuart; Gawande, Atul A.; Block, Susan D.] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Bernacki, Rachelle; Block, Susan D.] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA 02115 USA. [Vick, Judith] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Smith, Grant] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Bernacki, R (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM rbernacki@partners.org FU Charina Endowment Fund; Partners Healthcare; Margaret T. Morris Foundation; Health Resources Services Administration [K01HP2046] FX This work was supported by the Charina Endowment Fund, Partners Healthcare, and the Margaret T. Morris Foundation. RB is supported by Health Resources Services Administration grant K01HP2046. NR 51 TC 12 Z9 12 U1 7 U2 10 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 2015 VL 5 IS 10 AR e009032 DI 10.1136/bmjopen-2015-009032 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA CX1PH UT WOS:000365467600096 PM 26443662 ER PT J AU Huang, J Huang, S Johnson, F Huang, F AF Huang, J. Huang, S. Johnson, F. Huang, F. TI MOLECULAR BASIS OF DIET, EXERCISE AND LIFESTYLE INTERVENTIONS IN ATHEROSCLEROTIC CARDIOVASCULAR DISEASE SO CARDIOLOGY LA English DT Meeting Abstract C1 [Huang, J.] St Louis Univ, Sch Med Biochem & Mol Biol, St Louis, MO USA. [Huang, S.] Auxagen Inc, Res, St Louis, MO USA. [Johnson, F.] St Louis Univ, Sch Med, Surg, St Louis, MO USA. [Huang, F.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Broad Inst Harvard & MIT,Dept Med Oncol, Boston, MA 02115 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 2015 VL 132 SU 1 MA 164 BP 87 EP 87 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CX4KD UT WOS:000365668000081 ER PT J AU Jena, A Blumenthal, D Stevens, W Ton, T Chou, J Goldman, D AF Jena, A. Blumenthal, D. Stevens, W. Ton, T. Chou, J. Goldman, D. TI RESIDUAL BURDEN OF DYSLIPIDEMIA IN THE US AND POTENTIAL SOCIAL VALUE OF PCSK9 INHIBITORS IN HIGH RISK POPULATIONS SO CARDIOLOGY LA English DT Meeting Abstract C1 [Jena, A.] Harvard Univ, Sch Med, Hlth Care Policy, Boston, MA USA. [Blumenthal, D.] Massachusetts Gen Hosp, Internal Med, Boston, MA 02114 USA. [Stevens, W.] Precis Hlth Econ, Hlth Econ, Los Angeles, CA USA. [Ton, T.] Precis Hlth Econ, Hlth Analyt, Los Angeles, CA USA. [Chou, J.] Precis Hlth Econ, Hlth Serv Res, Los Angeles, CA USA. [Goldman, D.] Univ So Calif, Schaeffer Ctr, Los Angeles, CA 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 2015 VL 132 SU 1 MA 298 BP 213 EP 213 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CX4KD UT WOS:000365668000191 ER PT J AU Khan, AA McFadden, EP AF Khan, Asaad Akbar McFadden, Eugene Patrick TI Emergent Unilateral Renal Artery Stenting for Treatment of Flash Pulmonary Edema: Fact or Fiction? SO CASE REPORTS IN CARDIOLOGY LA English DT Article ID RENOVASCULAR HYPERTENSION; HEART-FAILURE; STENOSIS; ANGIOPLASTY; THERAPY AB Flash pulmonary edema is characteristically sudden in onset with rapid resolution once appropriate therapy has been instituted (Messerli et al., 2011). Acute increase of left ventricular (LV) end diastolic pressure is the usual cause of sudden decompensated cardiac failure in this patient population. Presence of bilateral renal artery stenosis or unilateral stenosis in combination with a single functional kidney in the susceptible cohort is usually blamed for this condition. We describe a patient who presented with flash pulmonary edema in the setting of normal coronary arteries. Our case is distinct as our patient developed flash pulmonary edema secondary to unilateral renal artery stenosis in the presence of bilateral functioning kidneys. Percutaneous stent implantation in the affected renal artery resulted in rapid resolution of pulmonary edema. C1 [Khan, Asaad Akbar] Massachusetts Gen Hosp, Cardiol Dept, Boston, MA 02114 USA. [Khan, Asaad Akbar] Cork Univ Hosp, Intervent Cardiol Dept, Cork, Ireland. [McFadden, Eugene Patrick] Cork Univ Hosp, Cork, Ireland. RP Khan, AA (reprint author), Massachusetts Gen Hosp, Cardiol Dept, Boston, MA 02114 USA. EM asaad.akbar@gmail.com NR 14 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-6404 EI 2090-6412 J9 CASE REP CARDIOL JI Case Rep. Cardiol. PY 2015 AR UNSP 659306 DI 10.1155/2015/659306 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CX1GH UT WOS:000365444000001 ER PT J AU Shen, Y Yin, ZF Fan, YB Chen, CF Dai, WJ Yi, WC Li, YQ Zhang, WT Zhang, YT Bian, R Huang, Y Machado, S Yuan, TF Shan, CL AF Shen, Ying Yin, Zhifei Fan, Yabei Chen, Chiun-Fan Dai, Wenjun Yi, Wenchao Li, Yongqiang Zhang, Wentong Zhang, Yuting Bian, Rong Huang, Yan Machado, Sergio Yuan, Ti-Fei Shan, Chunlei TI Comparison of the Effects of Contralaterally Controlled Functional Electrical Stimulation and Neuromuscular Electrical Stimulation on Upper Extremity Functions in Patients with Stroke SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Article DE Contralaterally controlled functional electrical stimulation; neuromuscular electrical stimulation; upper extremity function; stroke ID TRANSCRANIAL MAGNETIC STIMULATION; RANDOMIZED CONTROLLED-TRIAL; SUBACUTE STROKE; HAND FUNCTION; CHRONIC HEMIPLEGIA; MOTOR MEMORY; RECOVERY; EXCITABILITY; ACQUISITION; ACTIVATION AB Background: Contralaterally controlled functional electrical stimulation (CCFES) is an innovative method to improve upper extremity functions after stroke. Objective: To compare the effects of CCFES versus neuromuscular electrical stimulation (NMES) on the upper extremity functions in patients with stroke. Methods: Sixty patients with stroke were randomly assigned into CCFES group (n=30) or NMES group (n=30). All patients were also treated with conventional medical treatment and rehabilitation training. Patients in CCFES group received CCFES to the affected wrist extensors while the NMES group received NMES. The stimulus current was biphasic wave with a pulse duration of 200 mu s and a frequency of 60Hz. The electrical stimulation lasted for 20min per session, 5 sessions per week for 3 weeks. The intensity of the CCFES was based on the electromyography (EMG) value of the unaffected side while the subjects voluntarily extended their unaffected wrist slightly (<10% range of motion, ROM), moderately (about 50% ROM) and completely (100% ROM). Fugl-Meyer assessment (FMA), motricity index (MI), the Hong Kong version of functional test for the hemiplegic upper extremity (FTHUE-HK) and active range of motion (AROM) of wrist extension were measured before and after 3 weeks of treatment. Results: Compared with the baseline values, both groups showed significant improvements in all the measurements after treatment (p<0.05). Patients in CCFES group showed significantly higher upper extremity FMA, FTHUE-HK scores and AROM of wrist extension than those in NMES group (p<0.05). Conclusion: Compared with the conventional NMES, CCFES provides better recovery of upper extremity function in patients with stroke. C1 [Shen, Ying; Yin, Zhifei; Fan, Yabei; Dai, Wenjun; Yi, Wenchao; Li, Yongqiang; Zhang, Wentong; Zhang, Yuting; Bian, Rong; Shan, Chunlei] Nanjing Med Univ, Affiliated Hosp 1, Rehabil Med Ctr, Nanjing 210029, Jiangsu, Peoples R China. [Chen, Chiun-Fan] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Spaulding Neuromodulat Ctr, Charlestown, MA USA. [Chen, Chiun-Fan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. [Huang, Yan] Yixing Hongta Hosp, Yixing, Peoples R China. [Machado, Sergio] Univ Fed Rio de Janeiro, Inst Psychiat, Rio De Janeiro, Brazil. [Machado, Sergio] Univ Salgado de Oliveira, Phys Act & Neurosci Lab, Niteroi, RJ, Brazil. [Yuan, Ti-Fei] Nanjing Normal Univ, Sch Psychol, Nanjing, Jiangsu, Peoples R China. [Shan, Chunlei] Shanghai Univ Tradit Chinese Med, Shanghai, Peoples R China. RP Shan, CL (reprint author), Nanjing Med Univ, Affiliated Hosp 1, Rehabil Med Ctr, 300 Guangzhou Rd, Nanjing 210029, Jiangsu, Peoples R China. EM ytf0707@126.com; shanclhappy@163.com FU National Natural Science Foundation [81171853, 81472163]; Six Talents Peak Project of Jiangsu Province [2011-WS-100]; Jiangsu Province Health Development Project with Science and Education; Priority Academic Program Development of Jiangsu Higher Education Institutions; Nanjing Normal University; Jiangsu Provincial Natural Science Foundation [BK20140917] FX This work was supported by National Natural Science Foundation (No. 81171853,81472163), Six Talents Peak Project of Jiangsu Province (No. 2011-WS-100), Jiangsu Province Health Development Project with Science and Education, the Priority Academic Program Development of Jiangsu Higher Education Institutions. The study is also supported by "Hundred Talents program", "Qing Lan Project" of Nanjing Normal University and Jiangsu Provincial Natural Science Foundation (No. BK20140917) (TY). NR 24 TC 1 Z9 1 U1 1 U2 6 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1871-5273 EI 1996-3181 J9 CNS NEUROL DISORD-DR JI CNS Neurol. Disord.-Drug Targets PY 2015 VL 14 IS 10 BP 1260 EP 1266 DI 10.2174/1871527315666151111122457 PG 7 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CX6JW UT WOS:000365808000003 PM 26556084 ER PT J AU Yin, ZF Shen, Y Reinhardt, JD Chen, CF Jiang, XY Dai, WJ Zhang, WT Machado, S Arias-Carrion, O Yuan, TF Shan, CL AF Yin, Zhifei Shen, Ying Reinhardt, Jan Dietrich Chen, Chiun-Fan Jiang, Xueyong Dai, Wenjun Zhang, Wenting Machado, Sergio Arias-Carrion, Oscar Yuan, Ti-Fei Shan, Chunlei TI 5 Hz Repetitive Transcranial Magnetic Stimulation with Maximum Voluntary Muscle Contraction Facilitates Cerebral Cortex Excitability of Normal Subjects SO CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS LA English DT Article DE Repetitive transcranial magnetic stimulation; motor evoked potentials; maximum voluntary muscle contraction; primary motor cortex area ID MOTOR CORTEX; CORTICAL STIMULATION; STROKE; PLASTICITY; RTMS; BRAIN; REHABILITATION; RECOVERY; ADULTS; NERVE AB Background: Recently, high-frequency repetitive transcranial magnetic stimulation (rTMS) is reported to evaluating the corticospinal pathway and improving both cortical excitability and motor function significantly in subjects. According to some previous reports, the maximum voluntary muscle contraction (MVC) of target muscle can reinforce the influence by rTMS. The aim of this study was to confirm 5 Hz rTMS with MVC in healthy individuals is an effective method to facilitate motor neuron excitability and the efficiency can last at least 30min post stimulation. Objective: To compare the motor evoked potentials (MEPs) elicited by 5Hz rTMS and 5Hz rTMS combined with MVC. Methods: In this randomized, controlled, assessor-blinded, crossover trial, 40 healthy right-handed subjects were divided into group A (n=20) and group B (n=20). All subjects received rTMS over the primary motor cortex area (M1) in the left hemisphere. The parameters of rTMS were 5 Hz, 90% of the resting motor threshold (RMT), for a total of 500 pulses in 100 trains (1-sec inter-stimulus and 8-sec inter-interval). Method 1: All subjects received rTMS over the hand area of left M1. Method 2: All subjects received rTMS at the same stimulated point, combined with maximum voluntary hand griping in each 10 trains. Test 1: group A underwent method 1, while group B underwent method 2. Test 2: A week later, group B underwent method 1, while group A underwent method 2. In each test, the MEP amplitude and latency was measured before (P-rTMS), 5min after (Post 1) and 30min after (Post 2) the rTMS intervention. Results: MEP amplitude increased significantly from baseline at 5 minutes post intervention under both treatment regimes. However for both sequences, it decreased towards baseline under the rTMS intervention at 30 minutes post intervention but remained relatively high when rTMS was combined with MVC. MEP latency decreased significantly from baseline at 5 minutes post intervention under both treatment regimes. For both sequences, it then increased again towards baseline under both treatment regimes at 30 minutes post intervention. Although there was a trend for a less pronounced increase under the combined treatment, this effect was not significant. Conclusion: Both 5Hz rTMS and 5Hz rTMS combined with MVC facilitate motor cortical excitability, but the enhancement in rTMS with MVC is more pronounced and maintained longer than simple rTMS. C1 [Yin, Zhifei; Shen, Ying; Jiang, Xueyong; Dai, Wenjun; Zhang, Wenting; Shan, Chunlei] Nanjing Med Univ, Affiliated Hosp 1, Dept Rehabil Med, 300 Guangzhou Rd, Nanjing 210029, Jiangsu, Peoples R China. [Reinhardt, Jan Dietrich] Sichuan Univ, Inst Disaster Management & Reconstruct, Rehabil Med Dept, Chengdu 610064, Peoples R China. [Reinhardt, Jan Dietrich] Hong Kong Polytech Univ, Chengdu, Peoples R China. [Reinhardt, Jan Dietrich] Swiss Parapleg Res, Nottwil, Switzerland. [Reinhardt, Jan Dietrich] Univ Lucerne, Dept Hlth Sci & Hlth Policy, Luzern, Switzerland. [Chen, Chiun-Fan] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Spaulding Neuromodulat Ctr, Charlestown, MA USA. [Chen, Chiun-Fan] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. [Machado, Sergio] Univ Fed Rio de Janeiro, Inst Psychiat, Lab Pan & Respirat, Rio De Janeiro, Brazil. [Machado, Sergio] Univ Salgado de Oliveira, Phys Act Neurosci Lab, Phys Act Sci Postgrad Program, Niteroi, RJ, Brazil. [Arias-Carrion, Oscar] Univ Salgado de Oliveira, Phys Act Neurosci Lab, Niteroi, RJ, Brazil. [Yuan, Ti-Fei] Nanjing Normal Univ, Sch Psychol, Nanjing, Jiangsu, Peoples R China. [Shan, Chunlei] Shanghai Univ Tradit Chinese Med, Shanghai, Peoples R China. RP Shan, CL (reprint author), Nanjing Med Univ, Affiliated Hosp 1, Dept Rehabil Med, 300 Guangzhou Rd, Nanjing 210029, Jiangsu, Peoples R China. EM ytf0707@126.com; shanclhappy@163.com FU National Natural Science Foundation of China [81171853, 81472163]; Jiangsu Provincial Natural Science Foundation [BK2011850, BK20140917]; Six Talents Peak Project of Jiangsu Province [N2011-WS-100]; Jiangsu Provincial Special Program of Medical Science [BL2012029]; Hundred Talents program; "Qing Lan Project" of Nanjing Normal University; Jiangsu Province Health Development Project with Science and Education FX The study was supported by National Natural Science Foundation of China (No. 81171853, No. 81472163), Jiangsu Provincial Natural Science Foundation (No. BK2011850), Six Talents Peak Project of Jiangsu Province (No. N2011-WS-100), Fund of Jiangsu Province Health Development Project with Science and Education, Jiangsu Provincial Special Program of Medical Science (BL2012029) (CS). The study is also supported by "Hundred Talents program", "Qing Lan Project" of Nanjing Normal University and Jiangsu Provincial Natural Science Foundation (No. BK20140917) (TY). NR 31 TC 1 Z9 1 U1 1 U2 3 PU BENTHAM SCIENCE PUBL PI BUSUM PA PO BOX 294, BUSUM, 1400 AG, NETHERLANDS SN 1871-5273 EI 1996-3181 J9 CNS NEUROL DISORD-DR JI CNS Neurol. Disord.-Drug Targets PY 2015 VL 14 IS 10 BP 1298 EP 1303 DI 10.2174/1871527315666151111124216 PG 6 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CX6JW UT WOS:000365808000009 PM 26556078 ER PT J AU Poon, SH Sim, K Baldessarini, RJ AF Poon, Shi Hui Sim, Kang Baldessarini, Ross J. TI Pharmacological Approaches for Treatment-resistant Bipolar Disorder SO CURRENT NEUROPHARMACOLOGY LA English DT Article DE Bipolar disorder; depression; experimental treatments; mania; treatment-resistance ID PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIALS; PROOF-OF-CONCEPT; ADD-ON THERAPY; DOUBLE-BLIND; II DEPRESSION; FOLLOW-UP; ANTIDEPRESSANT TREATMENT; ADJUNCTIVE MODAFINIL; AUGMENTATION THERAPY AB Bipolar disorder is prevalent, with high risks of disability, substance abuse and premature mortality. Treatment responses typically are incomplete, especially for depressive components, so that many cases can be considered "treatment resistant." We reviewed reports on experimental treatments for such patients: there is a striking paucity of such research, mainly involving small incompletely controlled trials of add-on treatment, and findings remain preliminary. Encouraging results have been reported by adding aripiprazole, bupropion, clozapine, ketamine, memantine, pramipexole, pregabalin, and perhaps tri-iodothyronine in resistant manic or depressive phases. The urgency of incomplete responses in such a severe illness underscores the need for more systematic, simpler, and better controlled studies in more homogeneous samples of patients. C1 [Poon, Shi Hui; Sim, Kang] Inst Mental Hlth, Dept Gen Psychiat, Singapore 539747, Singapore. [Poon, Shi Hui; Sim, Kang] Inst Mental Hlth, Div Res, Singapore 539747, Singapore. [Baldessarini, Ross J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,McLean Div, Dept Psychiat,Int Consortium Bipolar Disorder Res, Boston, MA USA. RP Sim, K (reprint author), Inst Mental Hlth, Dept Gen Psychiat, 10 Buangkok View, Singapore 539747, Singapore. EM kang_sim@imh.com.sg NR 104 TC 0 Z9 0 U1 3 U2 5 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-159X EI 1875-6190 J9 CURR NEUROPHARMACOL JI Curr. Neuropharmacol. PY 2015 VL 13 IS 5 BP 592 EP 604 DI 10.2174/1570159X13666150630171954 PG 13 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA CX3UW UT WOS:000365625900004 ER PT J AU Channick, RN Delcroix, M Ghofrani, HA Hunsche, E Jansa, P Le Brun, FO Mehta, S Pulido, T Rubin, LJ Sastry, BKS Simonneau, G Sitbon, O Souza, R Torbicki, A Galie, N AF Channick, Richard N. Delcroix, Marion Ghofrani, Hossein-Ardeschir Hunsche, Elke Jansa, Pavel Le Brun, Franck-Olivier Mehta, Sanjay Pulido, Tomas Rubin, Lewis J. Sastry, B. K. S. Simonneau, Gerald Sitbon, Olivier Souza, Rogerio Torbicki, Adam Galie, Nazzareno TI Effect of Macitentan on Hospitalizations: Results From the SERAPH IN Trial SO JACC-HEART FAILURE LA English DT Article DE hospitalization; macitentan; pulmonary arterial hypertension ID PULMONARY ARTERIAL-HYPERTENSION; RECEPTOR ANTAGONIST; REVEAL REGISTRY; DOUBLE-BLIND; END-POINTS; BOSENTAN; THERAPY; SILDENAFIL; DIAGNOSIS; SURVIVAL AB OBJECTIVES This study sought to evaluate the effect of macitentan on hospitalization of patients with symptomatic pulmonary arterial hypertension (PAH). BACKGROUND PAH is a progressive, life-threatening disease often requiring hospitalization. METHODS In the multicenter, double-blind, randomized, event-driven, phase III SERAPHIN (Study with an Endothelin Receptor Antagonist in Pulmonary arterial Hypertension to Improve cliNical outcome) trial, patients with symptomatic PAH were randomized (1:1:1) to receive placebo or 3 mg or 10 mg of macitentan. Effects of macitentan on the risk, rate, and number of hospital days for all-cause and PAH-related hospitalizations were compared with those for placebo. Risk and causes of hospitalizations unrelated to PAH were investigated. RESULTS Of 742 randomized patients, 250 received placebo, 250 received 3 mg of macitentan, and 242 received 10 mg of macitentan; the overall median duration of treatment was 115 weeks. Risk of all-cause hospitalization was reduced by 18.9% (p = 0.1208) and 32.3% (p = 0.0051) in the macitentan 3-mg and 10-mg arm, respectively. Rates of all-cause hospitalizations and numbers of hospital days were reduced by 20.5% (p = 0.0378) and 30.6% (p = 0.0278), respectively, with 3 mg of macitentan and by 33.1% (p = 0.0005) and 31.0% (p = 0.0336), respectively, with 10 mg of macitentan. Risk of PAH-related hospitalizations were reduced by 42.7% (p = 0.0015) and 51.6% (p < 0.0001) in the macitentan 3-mg and 10-mg arms, respectively. Rate of PAN-related hospitalizations and numbers of hospital days were reduced by 44.5% (p = 0.0004) and 53.3% (p = 0.0001), respectively, with 3 mg of macitentan, and reduced by 49.8% (p < 0.0001) and 52.3% (p = 0.0003), respectively, with 10 mg of macitentan. Risk of non-PAH-related hospitalization was similar between treatment arms. CONCLUSIONS Macitentan 10 mg significantly reduced the risk and rate of all-cause hospitalization, which was driven by reductions in the risk and rate of PAH-related hospitalization. (Study of Macitentan [ACT-064992] on Morbidity and Mortality in Patients With Symptomatic Pulmonary Arterial Hypertension; NCT:00660179) (C) 2015 by the American College of Cardiology Foundation. C1 [Channick, Richard N.] Massachusetts Gen Hosp, Pulm & Crit Care, Boston, MA 02114 USA. [Delcroix, Marion] Univ Hosp Gasthuisberg, Dept Pneumol, Leuven, Belgium. [Ghofrani, Hossein-Ardeschir] UGMLC, Giessen, Germany. [Ghofrani, Hossein-Ardeschir] Univ London Imperial Coll Sci Technol & Med, Dept Med, London, England. [Hunsche, Elke; Le Brun, Franck-Olivier] Actel Pharmaceut Ltd, Allschwil, Switzerland. [Jansa, Pavel] Charles Univ Prague, Dept Med 2, Fac Med 1, Clin Dept Cardiol & Angiol, Prague, Czech Republic. [Mehta, Sanjay] Univ Western Ontario, London Hlth Sci Ctr, Victoria Hosp, Div Respirol,Dept Med, London, ON, Canada. [Pulido, Tomas] Ignacio Chavez Natl Heart Inst, Cardiopulm Dept, Mexico City, DF, Mexico. [Rubin, Lewis J.] Univ Calif San Diego, Sch Med, Div Pulm & Crit Care Med, San Diego, CA 92103 USA. [Sastry, B. K. S.] CARE Hosp, Dept Cardiol, Hyderabad, Andhra Pradesh, India. [Simonneau, Gerald; Sitbon, Olivier] Hop Bicetre, AP HP, Serv Pneumol, Le Kremlin Bicetre, France. [Simonneau, Gerald; Sitbon, Olivier] Univ Paris 11, Lab Excellence Rech Medicament & Innovat Therapeu, Le Kremlin Bicetre, France. [Simonneau, Gerald; Sitbon, Olivier] Ctr Chirurg Marie Lannelongue, INSERM U999, Le Plessis Robinson, France. [Souza, Rogerio] Univ Sao Paulo, Sch Med, Inst Heart, Dept Pulm, Sao Paulo, Brazil. [Torbicki, Adam] Med Ctr Postgrad Educ, Dept Pulm Circulat & Thromboembol Dis, Ecz Otwock, Poland. [Galie, Nazzareno] Bologna Univ Hosp, Dept Expt Diagnost & Specialty Med DIMES, Bologna, Italy. RP Channick, RN (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA. EM rchannick@mgh.harvard.edu OI Galie, Nazzareno/0000-0003-4271-8670 FU Actelion Pharmaceuticals Ltd. FX Medical writing was provided by Liesje Quine, PhD, and Lisa Thomas, PhD, Elements Communications, Ltd., Westerham, United Kingdom, and funded by Actelion Pharmaceuticals Ltd. NR 26 TC 19 Z9 19 U1 0 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1779 EI 2213-1787 J9 JACC-HEART FAIL JI JACC-Heart Fail. PD JAN PY 2015 VL 3 IS 1 BP 1 EP 8 DI 10.1016/j.jchf.2014.07.013 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CX4DV UT WOS:000365649700001 PM 25457902 ER PT J AU Chatterjee, NA Lewis, GD AF Chatterjee, Neal A. Lewis, Gregory D. TI Characterization of Pulmonary Hypertension in Heart Failure Using the Diastolic Pressure Gradient Limitations of a Solitary Measurement SO JACC-HEART FAILURE LA English DT Editorial Material DE congestive heart failure; pulmonary circulation and disease ID PRESERVED EJECTION FRACTION; ARTERY PRESSURE; DILATED CARDIOMYOPATHY; INTERNATIONAL SOCIETY; LUNG TRANSPLANTATION; PROGNOSTIC VALUE; THERAPY; HEMODYNAMICS; MORTALITY; COMMUNITY C1 [Chatterjee, Neal A.; Lewis, Gregory D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Cardiol, Boston, MA 02115 USA. [Lewis, Gregory D.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit,Dept Med, Boston, MA 02115 USA. RP Lewis, GD (reprint author), Massachusetts Gen Hosp, Heart Failure & Cardiac Transplantat Unit, Bigelow 800,Fruit St, Boston, MA 02114 USA. EM glewis@partners.org FU PHS HHS [NHLBI R01HL119154] NR 29 TC 13 Z9 14 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1779 EI 2213-1787 J9 JACC-HEART FAIL JI JACC-Heart Fail. PD JAN PY 2015 VL 3 IS 1 BP 17 EP 21 DI 10.1016/j.jchf.2014.09.002 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CX4DV UT WOS:000365649700003 PM 25453537 ER PT J AU Ahmad, T Wang, T O'Brien, EC Samsky, MD Pura, JA Lokhnygina, Y Rogers, JG Hernandez, AF Craig, D Bowles, DE Milano, CA Shah, SH Januzzi, JL Felker, M Patel, CB AF Ahmad, Tariq Wang, Teresa O'Brien, Emily C. Samsky, Marc D. Pura, John A. Lokhnygina, Yuliya Rogers, Joseph G. Hernandez, Adrian F. Craig, Damian Bowles, Dawn E. Milano, Carmelo A. Shah, Svati H. Januzzi, James L. Felker, Michael Patel, Chetan B. TI Effects of Left Ventricular Assist Device Support on Biomarkers of Cardiovascular Stress, Fibrosis, Fluid Homeostasis, Inflammation, and Renal Injury SO JACC-HEART FAILURE LA English DT Article DE biomarkers; heart failure; LVAD; myocardial recovery ID CHRONIC HEART-FAILURE; GROWTH-DIFFERENTIATION FACTOR-15; GELATINASE-ASSOCIATED LIPOCALIN; NATRIURETIC-PEPTIDE; PROGNOSTIC VALUE; CONTINUOUS-FLOW; MYOCARDIAL FIBROSIS; AMBULATORY PATIENTS; MULTIPLE BIOMARKERS; TIME-COURSE AB OBJECTIVES The purpose of this study was to examine changes in a broad panel of biomarkers following left ventricular assist device (LVAD) support in advanced heart failure (HF). BACKGROUND LVAD therapy mechanically unloads the failing heart and may result in reversal of certain aspects of the end-stage HF phenotype. Changes in markers of myocardial stress, fibrosis, inflammation, fluid homeostasis, and renal injury in this setting are unknown. METHODS Amino-terminal pro-B-type natriuretic peptide (NT-proBNP), galectin-3, ST2, copeptin, growth differentiation factor (GDF)-15, C-reactive protein (CRP), and neutrophil gelatinase associated lipocalin (NGAL) levels were measured in frozen plasma collected from 37 individuals prior to continuous flow LVAD implantation and a median of 136 (interquartile range: 94 to 180) days after implantation. RESULTS The median age of patients was 68 years old. LVAD therapy was associated with significant decreases in NT-proBNP (3,093 to 2,090 pg/ml; p = 0.02), ST2 (67.5 to 45.2 ng/ml, p <0.01), galectin-3 (24.7 to 22.0 ng/ml; p = 0.04), GDF-15 (3,232 to 2,613 ng/l,p <0.001), hs-CRP (22.4 to 11.9 mg/l; p = 0.01), and copeptin (103 to 94 pmol/l; p = 0.003) but not NGAL (132 to 135 ng/ml; p = 0.06). Despite improvement over time, absolute values of each biomarker remained extremely abnormal. Greater reductions in biomarkers were noted in individuals with >25% decrease in NT-proBNP concentrations but reached statistical significance only in the case of galectin-3 (p = 0.01). CONCLUSIONS The biomarker profile in patients after LVAD placement improves but nonetheless remains significantly abnormal. Our results suggest the need for targeted therapeutic interventions to mitigate such abnormalities and potentially increase rates of myocardial recovery. (C) 2015 by the American College of Cardiology Foundation. C1 [Ahmad, Tariq; Rogers, Joseph G.; Hernandez, Adrian F.; Shah, Svati H.; Felker, Michael; Patel, Chetan B.] Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA. [Ahmad, Tariq; Wang, Teresa; O'Brien, Emily C.; Pura, John A.; Lokhnygina, Yuliya; Rogers, Joseph G.; Hernandez, Adrian F.; Shah, Svati H.; Felker, Michael; Patel, Chetan B.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27710 USA. [Samsky, Marc D.] Duke Univ, Med Ctr, Dept Internal Med, Durham, NC 27710 USA. [Craig, Damian; Shah, Svati H.] Duke Univ, Med Ctr, Duke Mol Physiol Inst, Durham, NC 27710 USA. [Bowles, Dawn E.; Milano, Carmelo A.] Duke Univ, Med Ctr, Div Cardiac Surg, Durham, NC 27710 USA. [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Patel, CB (reprint author), Duke Univ, Med Ctr, Dept Med, Div Cardiol, DUMC 3034, Durham, NC 27710 USA. EM chetan.patel@duke.edu RI Hernandez, Adrian F./A-7818-2016 OI Hernandez, Adrian F./0000-0003-3387-9616 FU Daland Fellowship in Clinical Investigation; Thoratec; BG Medicine; Critical Diagnostics; Roche Diagnostics; Roche; Siemens; Singulex; Thermo Fisher; Medtronic, Inc.; BMS; Janssen; Portola; Novartis FX This study was supported by a grant from the Daland Fellowship in Clinical Investigation. Dr. Ahmad has received a travel scholarship from Thoratec; and support from the Daland Fellowship in Clinical Investigation. Dr. Felker has received research funding from BG Medicine, Critical Diagnostics, and Roche Diagnostics; and has served as a consultant for Roche Diagnostics and Singulex. Dr. Januzzi has served as consultant for Critical Diagnostics and Novartis; has received grants from Roche, Siemens, Singulex, and Thermo Fisher; and is on the endpoint committee for Amgen, Boehringer Ingelheim, and Novartis. Dr. Shah holds an unlicensed patent on metabolomic findings; and has received research funding from Medtronic, Inc. Dr. Hernandez has financial research relationships with BMS, Janssen, Portola, and Novartis. NR 38 TC 12 Z9 12 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1779 EI 2213-1787 J9 JACC-HEART FAIL JI JACC-Heart Fail. PD JAN PY 2015 VL 3 IS 1 BP 30 EP 39 DI 10.1016/j.jchf.2015.06.013 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CX4DV UT WOS:000365649700005 PM 25447345 ER PT J AU Tang, WHW Dupont, M Hernandez, AF Voors, AA Hsu, AP Felker, GM Butler, J Metra, M Anker, SD Troughton, RW Gottlieb, SS McMurray, JJ Armstrong, PW Massie, BM Califf, RM O'Connor, CM Starling, RC AF Tang, W. H. Wilson Dupont, Matthias Hernandez, Adrian F. Voors, Adriaan A. Hsu, Amy P. Felker, G. Michael Butler, Javed Metra, Marco Anker, Stefan D. Troughton, Richard W. Gottlieb, Stephen S. McMurray, John J. Armstrong, Paul W. Massie, Barry M. Califf, Robert M. O'Connor, Christopher M. Starling, Randall C. TI Comparative Assessment of Short-Term Adverse Events in Acute Heart Failure With Cystatin C and Other Estimates of Renal Function: Results From the ASCEND-HF Trial SO JACC-HEART FAILURE LA English DT Article DE acute heart failure; cystatin C; nesiritide; renal insufficiency ID GLOMERULAR-FILTRATION-RATE; ACUTE KIDNEY INJURY; CARDIORENAL SYNDROME; CREATININE EQUATION; SERUM CREATININE; NT-PROBNP; RISK; NESIRITIDE; MARKERS; IMPACT AB OBJECTIVES The purpose of this study was to investigate the predictive values of baseline and changes in cystatin C (CysC) and its derived equations for short-term adverse outcomes and the effect of nesiritide therapy on CysC in acute decompensated heart failure (ADHF). BACKGROUND Newer renal. biomarkers or their derived estimates of renal function have demonstrated tong-term prognostic value in chronic heart failure. METHODS CysC levels were measured in sequential plasma samples from 811 subjects with ADHF who were enrolled in the ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) biomarker sub-study (randomized to nesiritide therapy vs. placebo), and followed for all-cause death (180 days) and recurrent hospital stay (30 days). RESULTS Median CysC levels were 1.49 (interquartile range [IQR]: 1.20 to 1.96) mg/l at baseline, 1.56 (IQR: 1.28 to 2.13) mg/l. at 48 to 72 h, and 1.58 (IQR: 1.24 to 2.11) mg/l. at 30 days. Higher baseline (but not follow-up) CysC levels were associated with increased risk of 30-day adverse events and less improvement in dyspnea after 24 h as welt as 180-day mortality, although not incremental to blood urea nitrogen. Worsening renal function (defined as a 0.3 mg/l increase in CysC) occurred in 161 of 701 (23%) patients, but it was not predictive of adverse events. Changes in CysC levels were similar between the nesiritide and placebo groups. CONCLUSIONS Our findings confirmed the prognostic value of baseline CysC levels in the setting of ADHF. However, worsening renal, function based on CysC rise was not predictive of adverse events. Nesiritide did not worsen renal function compared with placebo. (C) 2015 by the American College of Cardiology Foundation. C1 [Tang, W. H. Wilson; Hsu, Amy P.; Starling, Randall C.] Cleveland Clin, Inst Heart & Vasc, Cleveland, OH 44195 USA. [Dupont, Matthias] Ziekenhuis Oost Limburg, Dept Cardiol, Genk, Belgium. [Hernandez, Adrian F.; Felker, G. Michael; Califf, Robert M.; O'Connor, Christopher M.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Butler, Javed] SUNY Stony Brook, Div Cardiovasc, Stony Brook, NY 11794 USA. [Metra, Marco] Univ Brescia, Dept Cardiol, Brescia, Italy. [Anker, Stefan D.] Univ Med Ctr Gottingen, Dept Innovat Clin Trials, Gottingen, Germany. [Troughton, Richard W.] Univ Otago, Dept Cardiol, Christchurch, New Zealand. [Gottlieb, Stephen S.] Univ Maryland, Dept Cardiol, Baltimore, MD 21201 USA. [McMurray, John J.] Univ Glasgow, Dept Cardiol, Glasgow, Lanark, Scotland. [Armstrong, Paul W.] Univ Alberta, Dept Cardiol, Edmonton, AB, Canada. [Massie, Barry M.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. RP Tang, WHW (reprint author), Cleveland Clin, 950 Euclid Ave,Desk J3-4, Cleveland, OH 44195 USA. EM tangw@ccf.org RI Hernandez, Adrian F./A-7818-2016; OI Hernandez, Adrian F./0000-0003-3387-9616; Metra, Marco/0000-0001-6691-8568; mcmurray, john/0000-0002-6317-3975 FU Janssen Pharmaceuticals, Inc.; Johnson Johnson; Roche Diagnostics; Critical Diagnostics; BG Medicine; Ortho Biotech FX The ASCEND-HF biomarker substudy is funded by Johnson & Johnson (now Janssen Pharmaceuticals, Inc.). Dr. Felker has received research grants from Johnson & Johnson, Roche Diagnostics, Critical Diagnostics, and BG Medicine. Dr. Hernandez has received a research grant from Johnson & Johnson. Drs. Gottlieb, Voors, Butler, and Massie are consultants to and on the advisory board of Johnson & Johnson. Dr. Metra is a consultant to and on the advisory board of Corthera, Daiichi, Novartis, and Servier. Dr. Anker has received honoraria from, is a consultant to, and is on the advisory board of Alere Inc., Europe, ThermoFisher Scientific, and Vifor Pharma. Dr. Troughton is a consultant to and on the advisory board of St. Jude Medical. Drs. McMurray, Califf, and O'Connor have received research grants from Johnson & Johnson. Dr. Armstrong has received research grants from Johnson & Johnson and Ortho Biotech. Dr. Starling has received other research support, is a consultant to, and on the advisory board of Johnson & Johnson. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. John R. Teerlink, MD, served as Guest Editor for this paper. NR 28 TC 10 Z9 10 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1779 EI 2213-1787 J9 JACC-HEART FAIL JI JACC-Heart Fail. PD JAN PY 2015 VL 3 IS 1 BP 40 EP 49 DI 10.1016/j.jchf.2014.06.014 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CX4DV UT WOS:000365649700006 PM 25453534 ER PT J AU Lax, A Sanchez-Mas, J Asensio-Lopez, MC Fernandez-Del Palacio, MJ Caballero, L Garrido, IP Pastor-Perez, FJ Januzzi, JL Pascual-Figal, DA AF Lax, Antonio Sanchez-Mas, Jesus Asensio-Lopez, Maria C. Fernandez-Del Palacio, Maria J. Caballero, Luis Garrido, Iris P. Pastor-Perez, Francisco J. Januzzi, James L. Pascual-Figal, Domingo A. TI Mineralocorticoid Receptor Antagonists Modulate Galectin-3 and Interleukin-33/ST2 Signaling in Left Ventricular Systolic Dysfunction After Acute Myocardial Infarction SO JACC-HEART FAILURE LA English DT Article DE eplerenone; heart failure; myocardial infarction; remodeling; spironolactone ID CHRONIC HEART-FAILURE; FAMILY-MEMBER ST2; SOLUBLE ST2; CARDIAC FIBROSIS; SERUM-LEVELS; TASK-FORCE; SPIRONOLACTONE; ALDOSTERONE; EPLERENONE; ASSOCIATION AB OBJECTIVES This study aimed to evaluate the specific role of the 2 available mineralocorticoid receptor antagonists (MRAs), epterenone and spironolactone, on the modulation of gatectin-3 (Gal-3) and interteukin (IL)-33/ST2 signaling in an experimental model of left ventricular systolic dysfunction after acute myocardial infarction (MI). BACKGROUND The molecular mechanisms of benefits of MRAs in patients with left ventricular systolic dysfunction after MI not welt understood. METHODS MI and left ventricular systolic dysfunction were induced by permanent ligation of the anterior coronary artery in 45 mate Wistar rats, randomly assigned to no therapy (MI group, n = 15) or to receive MRAs (100 mg/kg/day) for 4 weeks; either epterenone (n = 15) or spironotactone (n = 15) was used. A sham group was used as a control (n = 8). Elements of the pathway for Gal-3 including transforming growth factor (TGF)-beta and SMAD3, as welt as that for IL-33/ST2 (including IL-33 and soluble ST2 [sST2]) were analyzed in the infarcted and noninfarcted myocardium by quantitative real-time reverse transcription potymerase chain reaction. Expression of markers of fibrosis (collagen types I and III, tissue inhibitor of metalloproteinase-1) and inflammation (IL-6, tumor necrosis factor-alpha, monocyte chemotactic protein-1) was also examined. RESULTS In the infarcted myocardium, compared with sham animals, the MI group had higher concentrations of Gal-3, TGF-beta, SMAD3, IL-33, and sST2, as welt as higher concentrations of markers of fibrosis and inflammation. Treatment with MRAs down-regulated Gal-3, TGF-beta, and SMAD3 and enhanced IL-33/ST2 signaling with tower expression of sST2; protective IL-33 up-regulation was unaffected by MRAs. Modulation of Gal-3 and IL-33/ST2 signaling induced by MRAs correlated with lower expression levels of fibrosis and inflammatory markers. No differences were found between epterenone and spironotactone. In the noninfarcted myocardium, compared with sham animals, the MI group exhibited a higher expression of Gal-3 and IL-33, but no signs of inflammation or fibrosis were observed; in the presence of MRAs, IL-33 expression was significantly up-regulated, but Gal-3 was unaffected. CONCLUSIONS MRAs play a pivotal rote in the Gal-3 and IL-33/ST2 modulation in post-MI cardiac remodeling. (C) 2015 by the American College of Cardiology Foundation. C1 [Lax, Antonio; Sanchez-Mas, Jesus; Asensio-Lopez, Maria C.; Caballero, Luis; Garrido, Iris P.; Pastor-Perez, Francisco J.; Pascual-Figal, Domingo A.] Univ Hosp Virgen de la Arrixaca, Dept Cardiol, Murcia 30120, Spain. [Lax, Antonio; Sanchez-Mas, Jesus; Asensio-Lopez, Maria C.; Pascual-Figal, Domingo A.] Univ Murcia, Sch Med, Dept Internal Med, Murcia, Spain. [Fernandez-Del Palacio, Maria J.] Univ Murcia, Dept Vet Med & Surg, Vet Teaching Hosp, Murcia, Spain. [Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Pascual-Figal, DA (reprint author), Univ Hosp Virgen de la Arrixaca, Dept Cardiol, Heart Failure Unit, Ctra Madrid Cartagena S-N, Murcia 30120, Spain. EM dpascual@um.es OI Pascual Figal, Domingo A./0000-0002-4993-9540 FU Fundacion Seneca, Murcia, Spain [11857/PI/09]; Ministerio de Sanidad, Madrid, Spain [PS09/02106]; National Network of Investigation in Cardiovascular Diseases [RD12/0042/0049] FX This study was supported in part by grant 11857/PI/09 from Fundacion Seneca, Murcia, Spain; by grant PS09/02106 from the Ministerio de Sanidad, Madrid, Spain; and by the National Network of Investigation in Cardiovascular Diseases RD12/0042/0049. All authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Lax and Sanchez-Mas contributed equally to this paper. NR 42 TC 20 Z9 22 U1 5 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1779 EI 2213-1787 J9 JACC-HEART FAIL JI JACC-Heart Fail. PD JAN PY 2015 VL 3 IS 1 BP 50 EP 58 DI 10.1016/j.jchf.2014.07.015 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CX4DV UT WOS:000365649700007 PM 25458175 ER PT J AU Reed, SC Partridge, AH Nekhlyudov, L AF Reed, Sarah C. Partridge, Ann H. Nekhlyudov, Larissa TI Shared Medical Appointments in Cancer Survivorship Care: A Review of the Literature SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Review ID ANDROGEN DEPRIVATION THERAPY; LONG-TERM SURVIVORS; PROSTATE-CANCER; BREAST-CANCER; MULTIDISCIPLINARY APPROACH; GROUP VISITS; PSYCHOLOGICAL DISTRESS; QUALITY IMPROVEMENT; TREATMENT DECISIONS; HEART-FAILURE AB Purpose: The physical and psychological effects of a cancer diagnosis and treatment on an individual may be significant and require appropriate monitoring and management. Furthermore, attention to preventive care and comorbid medical conditions is critical. Innovative approaches are needed to provide quality care to this growing population. Methods: We reviewed the literature evaluating shared medical appointments (SMAs) in noncancer and cancer care settings. Supported by a conceptual framework and adhering to the goals of patient-centered communication, we propose how SMAs may be used in clinical practice to enhance survivorship care. Results: The literature suggests that SMAs are an effective model in noncancer settings, showing improved blood pressure and health-related quality of life, among others. Although evidence for SMAs in cancer care is limited, there is significant potential for improved patient outcomes and costs. In particular, SMAs may provide an opportunity to address medical and psychological needs while creating a structure for enhanced communication. Conclusion: SMAs may offer an innovative care model for cancer survivors and their providers. Implementation and evaluation of SMAs in the care of cancer survivors is warranted. C1 Univ Calif Davis, Betty Irene Moore Sch Nursing, Davis, CA 95616 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. Harvard Vanguard Med Associates, Boston, MA USA. RP Reed, SC (reprint author), Educ Bldg,4610 10 St,Suite 4202, Sacramento, CA 95817 USA. EM screed@ucdavis.edu NR 84 TC 2 Z9 2 U1 2 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD JAN PY 2015 VL 11 IS 1 BP 6 EP 11 DI 10.1200/JOP.2014.001411 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CW9ZW UT WOS:000365357700018 PM 25424650 ER PT J AU Shulman, LN Ferris, L Takanishi, DM McKellar, D AF Shulman, Lawrence N. Ferris, Linda Takanishi, Danny M. McKellar, Daniel TI Treatment Summaries and Survivorship Care Plans: The Approach by the Commission on Cancer to Increase Use SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Editorial Material C1 Commiss Canc, Chicago, IL USA. [Shulman, Lawrence N.] Dana Farber Canc Inst, Boston, MA 02215 USA. Centura Hlth, Englewood, CO USA. Univ Hawaii, Honolulu, HI 96822 USA. Wayne HealthCare, Greenville, OH USA. RP Shulman, LN (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM lawrence_shulman@dfci.harvard.edu NR 7 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD JAN PY 2015 VL 11 IS 1 BP 40 EP + DI 10.1200/JOP.2014.002329 PG 3 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CW9ZW UT WOS:000365357700026 PM 25424651 ER PT J AU Partridge, AH Smith, IE Rumble, RB AF Partridge, Ann H. Smith, Ian E. Rumble, R. Bryan TI Chemo- and Targeted Therapy for Women With Human Epidermal Growth Factor Receptor 2-Negative (or unknown) Advanced Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Summary SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Royal Marsden Hosp, London SW3 6JJ, England. [Partridge, Ann H.] Amer Soc Clin Oncol, Alexandria, VA 22314 USA. RP Partridge, AH (reprint author), Amer Soc Clin Oncol, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA. EM guidelines@asco.org NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD JAN PY 2015 VL 11 IS 1 BP 42 EP + DI 10.1200/JOP.2014.001685 PG 3 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CW9ZW UT WOS:000365357700027 PM 25491044 ER PT J AU Al-Hebshi, NN Nasher, AT Idris, AM Chen, T AF Al-Hebshi, Nezar Noor Nasher, Akram Thabet Idris, Ali Mohamed Chen, Tsute TI Robust species taxonomy assignment algorithm for 16S rRNA NGS reads: application to oral carcinoma samples SO JOURNAL OF ORAL MICROBIOLOGY LA English DT Article DE bacteria; cancer; next-generation sequencing; OSCC; pyrosequencing; taxonomy ID SQUAMOUS-CELL CARCINOMA; BACTERIAL DIVERSITY; CANCER; SALIVA; SEQUENCES; ARB AB Background: Usefulness of next-generation sequencing (NGS) in assessing bacteria associated with oral squamous cell carcinoma (OSCC) has been undermined by inability to classify reads to the species level. Objective: The purpose of this study was to develop a robust algorithm for species-level classification of NGS reads from oral samples and to pilot test it for profiling bacteria within OSCC tissues. Methods: Bacterial 16S V1-V3 libraries were prepared from three OSCC DNA samples and sequenced using 454's FLX chemistry. High-quality, well-aligned, and non-chimeric reads >= 350 bp were classified using a novel, multi-stage algorithm that involves matching reads to reference sequences in revised versions of the Human Oral Microbiome Database (HOMD), HOMD extended (HOMDEXT), and Greengene Gold (GGG) at alignment coverage and percentage identity >= 98%, followed by assignment to species level based on top hit reference sequences. Priority was given to hits in HOMD, then HOMDEXT and finally GGG. Unmatched reads were subject to operational taxonomic unit analysis. Results: Nearly, 92.8% of the reads were matched to updated-HOMD 13.2, 1.83% to trusted-HOMDEXT, and 1.36% to modified-GGG. Of all matched reads, 99.6% were classified to species level. A total of 228 species-level taxa were identified, representing 11 phyla; the most abundant were Proteobacteria, Bacteroidetes, Firmicutes, Fusobacteria, and Actinobacteria. Thirty-five species-level taxa were detected in all samples. On average, Prevotella oris, Neisseria flava, Neisseria flavescens/subflava, Fusobacterium nucleatum ss polymorphum, Aggregatibacter segnis, Streptococcus mitis, and Fusobacterium periodontium were the most abundant. Bacteroides fragilis, a species rarely isolated from the oral cavity, was detected in two samples. Conclusion: This multi-stage algorithm maximizes the fraction of reads classified to the species level while ensuring reliable classification by giving priority to the human, oral reference set. Applying the algorithm to OSCC samples revealed high diversity. In addition to oral taxa, a number of human, non-oral taxa were also identified, some of which are rarely detected in the oral cavity. C1 [Al-Hebshi, Nezar Noor] Jazan Univ, Fac Dent, Dept Prevent Dent, Jazan, Saudi Arabia. [Nasher, Akram Thabet] Sanaa Univ, Fac Dent, Dept Oral & Maxillofacial Surg, Sanaa, Yemen. [Idris, Ali Mohamed] Jazan Univ, Fac Dent, Dept Maxillofacial Surg & Diagnost Sci, Jazan, Saudi Arabia. [Chen, Tsute] Forsyth Inst, Dept Microbiol, Cambridge, MA USA. RP Al-Hebshi, NN (reprint author), Jazan Univ, Fac Dent, Dept Prevent Dent, POB 114, Jazan, Saudi Arabia. EM nazhebshi@yahoo.com; tchen@forsyth.org RI Al-hebshi, Nezar/J-9180-2013 OI Al-hebshi, Nezar/0000-0003-1841-9304 FU Substance Abuse Research Center (SARC) at Jazan University, Saudi Arabia [1010/2010] FX The study was funded by the Substance Abuse Research Center (SARC) at Jazan University, Saudi Arabia (grant no. 1010/2010). NR 37 TC 9 Z9 9 U1 1 U2 2 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2000-2297 J9 J ORAL MICROBIOL JI J. Oral Microbiology PY 2015 VL 7 AR 28934 DI 10.3402/jom.v7.28934 PG 9 WC Microbiology SC Microbiology GA CX4VL UT WOS:000365698300001 PM 26426306 ER PT J AU Belstrom, D Fiehn, NE Nielsen, CH Klepac-Ceraj, V Paster, BJ Twetman, S Holmstrup, P AF Belstrom, Daniel Fiehn, Nils-Erik Nielsen, Claus H. Klepac-Ceraj, Vanja Paster, Bruce J. Twetman, Svante Holmstrup, Palle TI Differentiation of salivary bacterial profiles of subjects with periodontitis and dental caries SO JOURNAL OF ORAL MICROBIOLOGY LA English DT Article DE saliva; HOMIM; bacteria; periodontitis; dental caries ID MICROBE IDENTIFICATION MICROARRAY; REFRACTORY PERIODONTITIS; ADULTS; HEALTH; INDIVIDUALS; DIVERSITY; COHORT AB Bacterial profiles of saliva in subjects with periodontitis and dental caries have been demonstrated to differ from that of oral health. The aim of this comparative analysis of existing data generated by the Human Oral Microbe Identification Microarray (HOMIM) from 293 stimulated saliva samples was to compare bacterial profiles of saliva in subjects with periodontitis and dental caries. C1 [Belstrom, Daniel; Nielsen, Claus H.; Holmstrup, Palle] Univ Copenhagen, Sch Dent, Fac Hlth Sci, Sect Periodontol Microbiol & Community Dent, DK-2200 Copenhagen, Denmark. [Fiehn, Nils-Erik] Univ Copenhagen, Dept Int Hlth Immunol & Microbiol, Copenhagen, Denmark. [Nielsen, Claus H.] Univ Copenhagen Hosp, Rigshosp, Inst Inflammat Res, Dept Infect Dis & Rheumatol, DK-2100 Copenhagen, Denmark. [Klepac-Ceraj, Vanja] Wellesley Coll, Dept Biol Sci, Wellesley, MA 02181 USA. [Paster, Bruce J.] Forsyth Inst, Dept Microbiol, Cambridge, MA USA. [Paster, Bruce J.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Twetman, Svante] Univ Copenhagen, Fac Hlth Sci, Sect Cariol, Sch Dent, DK-2200 Copenhagen, Denmark. RP Belstrom, D (reprint author), Univ Copenhagen, Dept Odontol, Fac Hlth & Med Sci, Sect Periodontol Microbiol & Community Dent, Norre Alle 20, DK-2200 Copenhagen, Denmark. EM dbel@sund.ku.dk FU Danish Dental Association; Danish Foundation for Mutual Efforts in Dental Care; TrygFonden; Health Insurance Foundation; Simon Spies Foundation FX The authors declare no conflict of interest in this study. This study was supported financially by: the Danish Dental Association, the Danish Foundation for Mutual Efforts in Dental Care, TrygFonden, the Health Insurance Foundation, and the Simon Spies Foundation. NR 18 TC 7 Z9 8 U1 2 U2 9 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2000-2297 J9 J ORAL MICROBIOL JI J. Oral Microbiology PY 2015 VL 7 AR 27429 DI 10.3402/jom.v7.27429 PG 5 WC Microbiology SC Microbiology GA CX4VB UT WOS:000365697300001 PM 25854857 ER PT J AU Chalmers, NI Oh, K Hughes, CV Pradhan, N Kanasi, E Ehrlich, Y Dewhirst, FE Tanner, ACR AF Chalmers, Natalia I. Oh, Kevin Hughes, Christopher V. Pradhan, Nooruddin Kanasi, Eleni Ehrlich, Ygal Dewhirst, Floyd E. Tanner, Anne C. R. TI Pulp and plaque microbiotas of children with severe early childhood caries SO JOURNAL OF ORAL MICROBIOLOGY LA English DT Article DE 16S rRNA; culture; Streptococcus mutans; Parascardovia ID DENTAL-CARIES; PRIMARY TEETH; ORAL-HEALTH; ENDODONTIC INFECTIONS; MOLECULAR ANALYSIS; NECROTIC PULPS; BACTERIA; LESIONS; MICROFLORA; DISPARITIES AB Background and objective: Bacterial invasion into pulps of primary teeth can lead to infection and premature tooth loss in children. This pilot study aimed to explore whether the microbiota of carious exposures of dental pulps resembles that of carious dentin or that of infected root canals. Design: Children with severe early childhood caries were studied. Children were consented and extent of caries, plaque, and gingivitis measured. Bacteria were sampled from carious lesion biofilms and vital carious exposures of pulps, and processed by anaerobic culture. Isolates were characterized from partial sequences of the 16S rRNA gene and identified by comparison with taxa in the Human Oral Microbiome Database (http://www.HOMD.org). The microbiotas of carious lesions and dental pulps were compared using univariate and multivariate approaches. Results: The microbiota of cariously exposed pulps was similar in composition to that of carious lesion biofilms except that fewer species/taxa were identified from pulps. The major taxa identified belonged to the phyla Firmicutes (mainly streptococci) and Actinobacteria (mainly Actinomyces species). Actinomyces and Selenomonas species were associated with carious lesions whereas Veillonella species, particularly Veillonella dispar was associated with pulps. Other bacteria detected in pulps included Streptococcus mutans, Parascardovia denticolens, Bifidobacterium longum, and several Lactobacillus and Actinomyces species. By principal, component analysis pulp microbiotas grouped together, whereas those in caries biofilms were widely dispersed. Conclusions: We conclude that the microbiota of cariously exposed vital primary pulps is composed of a subset of species associated with carious lesions. Vital primary pulps had a dominant Firmicutes and Actinobacteria microbiota which contrasts with reports of endodontic infections which can harbor a gram-negative microbiota. The microbiota of exposed primary pulps may provide insight into bacterial species at the forefront of caries invasion in dentinal lesions that can invade into the pulp and the nature of species that need suppressing for successful pulp therapy. C1 [Chalmers, Natalia I.] NIDCR, NIH, Bethesda, MD USA. [Chalmers, Natalia I.; Kanasi, Eleni; Dewhirst, Floyd E.; Tanner, Anne C. R.] Forsyth Inst, Dept Microbiol, Cambridge, MA 02142 USA. [Oh, Kevin; Dewhirst, Floyd E.; Tanner, Anne C. R.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Hughes, Christopher V.; Kanasi, Eleni] Boston Univ, Goldman Sch Dent Med, Boston, MA 02215 USA. [Pradhan, Nooruddin] Tufts Univ, Sch Dent Med, Boston, MA 02111 USA. [Ehrlich, Ygal] Indiana Univ, Sch Dent, Indianapolis, IN USA. RP Tanner, ACR (reprint author), Forsyth Inst, Dept Microbiol, 245 First St, Cambridge, MA 02142 USA. EM annetanner@forsyth.org FU NIDCR at the National Institutes of Health [DE-015847, DE016937, T32-DE-007327] FX This study was performed with grants from NIDCR at the National Institutes of Health DE-015847, DE016937, and T32-DE-007327. NR 37 TC 6 Z9 6 U1 3 U2 9 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2000-2297 J9 J ORAL MICROBIOL JI J. Oral Microbiology PY 2015 VL 7 AR 25951 DI 10.3402/jom.v7.25951 PG 8 WC Microbiology SC Microbiology GA CX4UM UT WOS:000365695800001 PM 25651832 ER PT J AU Chen, T Siddiqui, H Olsen, I AF Chen, Tsute Siddiqui, Huma Olsen, Ingar TI Comparative genomics and proteomics of 13 Porphyromonas gingivalis strains SO JOURNAL OF ORAL MICROBIOLOGY LA English DT Editorial Material C1 [Chen, Tsute] Forsyth Inst, Dept Microbiol, Cambridge, MA 02142 USA. [Siddiqui, Huma; Olsen, Ingar] Univ Oslo, Dept Oral Biol, Oslo, Norway. RP Chen, T (reprint author), Forsyth Inst, Dept Microbiol, Cambridge, MA 02142 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2000-2297 J9 J ORAL MICROBIOL JI J. Oral Microbiology PY 2015 VL 7 AR 29008 DI 10.3402/jom.v7.29008 PG 1 WC Microbiology SC Microbiology GA CX4VM UT WOS:000365698400001 PM 26387643 ER PT J AU Macovei, L McCafferty, J Chen, T Teles, F Hasturk, H Paster, BJ Campos-Neto, A AF Macovei, Lilia McCafferty, Jon Chen, Tsute Teles, Flavia Hasturk, Hatice Paster, Bruce J. Campos-Neto, Antonio TI The hidden 'mycobacteriome' of the human healthy oral cavity and upper respiratory tract SO JOURNAL OF ORAL MICROBIOLOGY LA English DT Article DE oral microbiome; Mycobacterium; non-tuberculous-mycobacteria; periodontal disease ID BACILLUS-CALMETTE-GUERIN; NONTUBERCULOUS MYCOBACTERIA; LUNG-DISEASE; HETEROLOGOUS IMMUNITY; HUMAN MICROBIOME; TUBERCULOSIS; DIVERSITY; BCG; IDENTIFICATION; ENVIRONMENT AB The incidence of opportunistic non-tuberculous mycobacteria (NTM) infections has increased considerably in the past decades causing an array of infections, including respiratory and soft-tissue infections. NTM are ubiquitous and can be found in numerous environments, including households and water plants. However, NTM have not been reported to be associated with the healthy human oral microbiome. Since the oral cavity and upper respiratory track are the main ports of entry of microorganisms into the human body, elucidating NTM diversity and prevalence will assist in the assessment of the potential risks of infection elicited by these opportunistic pathogens. Here, we report the identification of a 'non-tuberculous mycobacteriome' in healthy individuals. We employed a modified DNA extraction procedure in conjunction with mycobacterial-specific primers to screen niches in the oral cavity (buccal mucosa and dental plaque) and upper respiratory tract (nostrils and oropharynx) of 10 healthy subjects. A total of 50 prevalent operational taxonomic units sequenced on MiSeq (Illumina) using 16S rRNA V3-V4 region were detected across all screened niches, showing the presence of diverse NTM communities. NTM DNA was detected in the nostrils of all 10 subjects, in buccal mucosa of 8 subjects, in the oropharynx of 7 subjects, and in the dental plaques of 5 subjects. Results from quantitative PCR showed each individual harbored 10(3) - 10(4) predicted NTM per each screened niche. The modification of standard DNA isolation methods to increase sensitivity toward mycobacterial species represents an important step to advance the knowledge of the oral as well as the overall human microbiome. These findings clearly reveal for the first time that healthy individuals harbor a non-tuberculous mycobacteriome' in their oral cavity and upper respiratory tract and may have important implications in our understanding of infections caused by NTM. C1 [Macovei, Lilia; McCafferty, Jon; Chen, Tsute; Teles, Flavia; Hasturk, Hatice; Paster, Bruce J.; Campos-Neto, Antonio] Forsyth Inst, Cambridge, MA 02142 USA. [Teles, Flavia; Paster, Bruce J.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Macovei, L (reprint author), Bioanalyt & Biomarker Dev, Shire 300 Shire Way, Lexington, MA 02421 USA. EM lmacovei@shire.com; acampos@forsyth.org FU Forsyth Institute; [R01 AI076425] FX This work was supported by Pilot Grant from The Forsyth Institute (LM) and R01 AI076425 (A.C-N.). NR 58 TC 1 Z9 1 U1 0 U2 3 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2000-2297 J9 J ORAL MICROBIOL JI J. Oral Microbiology PY 2015 VL 7 AR 26094 DI 10.3402/jom.v7.26094 PG 11 WC Microbiology SC Microbiology GA CX4UP UT WOS:000365696100001 PM 25683180 ER PT J AU Seoudi, N Bergmeier, LA Drobniewski, F Paster, B Fortune, F AF Seoudi, Noha Bergmeier, Lesley A. Drobniewski, Francis Paster, Bruce Fortune, Farida TI The oral mucosal and salivary microbial community of Behcet's syndrome and recurrent aphthous stomatitis SO JOURNAL OF ORAL MICROBIOLOGY LA English DT Article DE Behcet's syndrome; recurrent aphthous stomatitis; microbiota; oral mucosa; saliva ID STREPTOCOCCUS-SANGUIS; BACTERIAL DIVERSITY; DISEASE; PERIODONTITIS; SUBGINGIVAL; PATHOGENESIS; PROFILES; LESIONS; HEALTH; ULCERS AB Background: Behcet's syndrome (BS) is a multisystem immune-related disease of unknown etiology. Recurrent aphthous stomatitis (RAS) is characterized by the presence of idiopathic oral ulceration without extraoral manifestation. The interplay between the oral microbial communities and the immune response could play an important role in the etiology and pathogenesis of both BS and RAS. Objective: To investigate the salivary and oral mucosal microbial communities in BS and RAS. Methods: Purified microbial DNA isolated from saliva samples (54 BS, 25 healthy controls [HC], and 8 RAS) were examined by the human oral microbe identification microarray. Cultivable salivary and oral mucosal microbial communities from ulcer and non-ulcer sites were identified by matrix-assisted laser desorption/ionization time-of-flight analysis. Mycobacterium spp. were detected in saliva and in ulcer and non-ulcer oral mucosal brush biopsies following culture on Lowenstein-Jensen slopes and Mycobacterial Growth Indicator Tubes. Results: There was increased colonization with Rothia denticariosa of the non-ulcer sites of BS and RAS patients (p<0.05). Ulcer sites in BS were highly colonized with Streptococcus salivarius compared to those of RAS (p<0.05), and with Streptococcus sanguinis compared to HC (p<0.0001). Oral mucosa of HC were more highly colonized with Neisseria and Veillonella compared to all studied groups (p<0.0001). Conclusions: Despite the uncertainty whether the reported differences in the oral mucosal microbial community of BS and RAS are of causative or reactive nature, it is envisaged that restoring the balance of the oral microbial community of the ulcer sites may be used in the future as a new treatment modality for oral ulceration. C1 [Seoudi, Noha; Bergmeier, Lesley A.; Fortune, Farida] Queen Mary Univ London, Barts & London Sch Med & Dent, Inst Dent, Ctr Clin & Diagnost Oral Sci, London A1 2AD, England. [Drobniewski, Francis] Queen Mary Univ London, Barts & London Sch Med & Dent, Blizard Inst Cell & Mol Sci, Ctr Immunol & Infect Dis, London A1 2AD, England. [Drobniewski, Francis] Univ London Imperial Coll Sci Technol & Med, Dept Infect Dis, London, England. [Paster, Bruce] Forsyth Inst, Dept Microbiol, Boston, MA USA. [Paster, Bruce] Harvard Univ, Sch Dent Med, Dept Microbiol, Boston, MA 02115 USA. RP Fortune, F (reprint author), Queen Mary Univ London, Barts & London Sch Med & Dent, Inst Dent, Ctr Clin & Diagnost Oral Sci, London A1 2AD, England. EM f.fortune@qmul.ac.uk FU Centre for Clinical and Diagnostic Oral Sciences. Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom; EU FP7 Grant EUROGEN FX There are no conflicts of interest. This work was self-funded within the Centre for Clinical and Diagnostic Oral Sciences. Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom. The EU FP7 Grant EUROGEN to Professor Francis Drobniewski kindly funded the Mycobacterial study. NR 43 TC 4 Z9 5 U1 2 U2 4 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2000-2297 J9 J ORAL MICROBIOL JI J. Oral Microbiology PY 2015 VL 7 AR 27150 DI 10.3402/jom.v7.27150 PG 9 WC Microbiology SC Microbiology GA CX4UW UT WOS:000365696800001 PM 26037240 ER PT J AU Brastianos, PK AF Brastianos, Priscilla K. TI Genomic Characterization of Central Nervous System Metastases: Implications for Precision Medicine SO ONCOLOGIST LA English DT Meeting Abstract CT Chabner Colloquium: Collaboration in Cancer Drug Trials CY OCT 26-27, 2015 CL Boston, MA C1 [Brastianos, Priscilla K.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, 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 2015 VL 20 SU 2 MA 3 BP S2 EP S2 PG 1 WC Oncology SC Oncology GA CX9RJ UT WOS:000366042700004 ER PT J AU D'Andrea, AD AF D'Andrea, Alan D. TI Targeting DNA Repair in Cancer Therapy SO ONCOLOGIST LA English DT Meeting Abstract CT Chabner Colloquium: Collaboration in Cancer Drug Trials CY OCT 26-27, 2015 CL Boston, MA C1 [D'Andrea, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 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 2015 VL 20 SU 2 MA 5 BP S3 EP S3 PG 1 WC Oncology SC Oncology GA CX9RJ UT WOS:000366042700006 ER PT J AU Ellisen, LW AF Ellisen, Leif W. TI The "BRCA-Like" Phenotype in Cancer SO ONCOLOGIST LA English DT Meeting Abstract CT Chabner Colloquium: Collaboration in Cancer Drug Trials CY OCT 26-27, 2015 CL Boston, MA C1 [Ellisen, Leif W.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, 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 2015 VL 20 SU 2 MA 4 BP S2 EP S2 PG 1 WC Oncology SC Oncology GA CX9RJ UT WOS:000366042700005 ER PT J AU Flaherty, KT AF Flaherty, Keith T. TI Emerging Therapies to Optimize MAP Kinase Blockade and Intercept Compensatory Signaling SO ONCOLOGIST LA English DT Meeting Abstract CT Chabner Colloquium: Collaboration in Cancer Drug Trials CY OCT 26-27, 2015 CL Boston, MA C1 [Flaherty, Keith T.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 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 2015 VL 20 SU 2 MA 14 BP S7 EP S7 PG 1 WC Oncology SC Oncology GA CX9RJ UT WOS:000366042700015 ER PT J AU Jain, RK AF Jain, Rakesh K. TI Reengineering the Tumor Stroma to Improve Cancer Treatment: Bench to Bedside SO ONCOLOGIST LA English DT Meeting Abstract CT Chabner Colloquium: Collaboration in Cancer Drug Trials CY OCT 26-27, 2015 CL Boston, MA C1 [Jain, Rakesh K.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, 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 2015 VL 20 SU 2 MA 7 BP S4 EP S4 PG 1 WC Oncology SC Oncology GA CX9RJ UT WOS:000366042700008 ER PT J AU Kugel, S AF Kugel, Sita TI Loss of SIRT6 Reactivates the Oncofetal Protein Lin28b to Drive Pancreatic Cancer SO ONCOLOGIST LA English DT Meeting Abstract CT Chabner Colloquium: Collaboration in Cancer Drug Trials CY OCT 26-27, 2015 CL Boston, MA C1 [Kugel, Sita] Harvard Univ, Massachusetts Gen Hosp, Sch Med, 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 2015 VL 20 SU 2 MA 13 BP S6 EP S6 PG 1 WC Oncology SC Oncology GA CX9RJ UT WOS:000366042700014 ER PT J AU Miyamoto, DT AF Miyamoto, David T. TI Molecular Analysis of Circulating Tumor Cells in Prostate Cancer SO ONCOLOGIST LA English DT Meeting Abstract CT Chabner Colloquium: Collaboration in Cancer Drug Trials CY OCT 26-27, 2015 CL Boston, MA C1 [Miyamoto, David T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, 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 2015 VL 20 SU 2 MA 12 BP S6 EP S6 PG 1 WC Oncology SC Oncology GA CX9RJ UT WOS:000366042700013 ER PT J AU Mullally, A AF Mullally, Ann TI Preferentially Targeting the Malignant Hematopoietic Clone in Myeloproliferative Neoplasms SO ONCOLOGIST LA English DT Meeting Abstract CT Chabner Colloquium: Collaboration in Cancer Drug Trials CY OCT 26-27, 2015 CL Boston, MA C1 [Mullally, Ann] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, 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 2015 VL 20 SU 2 MA 11 BP S6 EP S6 PG 1 WC Oncology SC Oncology GA CX9RJ UT WOS:000366042700012 ER PT J AU Nipp, RD AF Nipp, Ryan D. TI The Lazarex-Massachusetts General Hospital Cancer Care Equity Program SO ONCOLOGIST LA English DT Meeting Abstract CT Chabner Colloquium: Collaboration in Cancer Drug Trials CY OCT 26-27, 2015 CL Boston, MA C1 [Nipp, Ryan D.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Dana Farber Harvard Canc Ctr,Sch Med, 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 2015 VL 20 SU 2 MA 10 BP S5 EP S5 PG 1 WC Oncology SC Oncology GA CX9RJ UT WOS:000366042700011 ER PT J AU Ramaswamy, S AF Ramaswamy, Sridhar TI Targeting Quiescent Cancer Cells SO ONCOLOGIST LA English DT Meeting Abstract CT Chabner Colloquium: Collaboration in Cancer Drug Trials CY OCT 26-27, 2015 CL Boston, MA C1 [Ramaswamy, Sridhar] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, 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 2015 VL 20 SU 2 MA 8 BP S4 EP S4 PG 1 WC Oncology SC Oncology GA CX9RJ UT WOS:000366042700009 ER PT J AU Zou, L AF Zou, Lee TI Alternative Lengthening of Telomeres Renders Cancer Cells Hypersensitive to ATR Inhibitors SO ONCOLOGIST LA English DT Meeting Abstract CT Chabner Colloquium: Collaboration in Cancer Drug Trials CY OCT 26-27, 2015 CL Boston, MA C1 [Zou, Lee] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, 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 2015 VL 20 SU 2 MA 6 BP S3 EP S3 PG 1 WC Oncology SC Oncology GA CX9RJ UT WOS:000366042700007 ER PT J AU Lee, SJ Fowler, JS Alexoff, D Schueller, M Kim, D Nauth, A Weber, C Kim, SW Hooker, JM Ma, L Qu, WC AF Lee, So Jeong Fowler, Joanna S. Alexoff, David Schueller, Michael Kim, Dohyun Nauth, Alexander Weber, Carina Kim, Sung Won Hooker, Jacob M. Ma, Ling Qu, Wenchao TI An efficient and practical synthesis of [2-C-11]indole via superfast nucleophilic [C-11]cyanation and RANEY (R) Nickel catalyzed reductive cyclization SO ORGANIC & BIOMOLECULAR CHEMISTRY LA English DT Article ID TRANSFER HYDROGENATION; INDOLES; CYANIDES; AUXIN AB A rapid method for the synthesis of carbon-11 radiolabeled indole was developed using a sub-nanomolar quantity of no-carrier-added [C-11] cyanide as radio-precursor. Based upon a reported synthesis of 2-(2-nitrophenyl)acetonitrile (2), a highly reactive substrate 2-nitrobenzyl bromide (1) was evaluated for nucleophilic [C-11] cyanation. Additionally, related reaction conditions were explored with the goal of obtaining of highly reactive 2-(2-nitrophenyl)-[1-C-11] acetonitrile ([C-11]-2) while inhibiting its rapid conversion to 2,3-bis(2-nitrophenyl)-[1-C-11] propanenitrile ([C-11]-3). Next, a RANEY(R) Nickel catalyzed reductive cyclization method was utilized for synthesizing the desired [2-C-11] indole with hydrazinium monoformate as the active reducing agent. Extensive and iterative screening of basicity, temperature and stoichiometry was required to overcome the large stoichiometry bias that favored 2-nitrobenzylbromide (1) over [C-11] cyanide, which both caused further alkylation of the desired nitrile and poisoned the RANEY(R) Nickel catalyst. The result is an efficient two-step, streamlined method to reliably synthesize [2-C-11] indole with an entire radiochemical yield of 21 +/- 2.2% (n = 5, ranging from 18-24%). The radiochemical purity of the final product was >98% and specific activity was 176 +/- 24.8 GBq mu mol(-1) (n = 5, ranging from 141-204 GBq mu mol(-1)). The total radiosynthesis time including product purification by semi-preparative HPLC was 50-55 min from end of cyclotron bombardment. C1 [Lee, So Jeong; Fowler, Joanna S.; Alexoff, David; Schueller, Michael; Kim, Dohyun; Nauth, Alexander; Weber, Carina; Kim, Sung Won; Hooker, Jacob M.; Qu, Wenchao] Brookhaven Natl Lab, Biol Environm & Climate Sci Dept, Upton, NY 11973 USA. [Lee, So Jeong] SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USA. [Nauth, Alexander; Weber, Carina] Johannes Gutenberg Univ Mainz, Inst Kernchem, D-55128 Mainz, Germany. [Hooker, Jacob M.; Ma, Ling] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Charlestown, MA 02129 USA. RP Qu, WC (reprint author), Brookhaven Natl Lab, Biol Environm & Climate Sci Dept, Upton, NY 11973 USA. EM wqu@bnl.gov FU U. S. Department of Energy, Office of Biological and Environmental Research within the Office of Science [DE-SC0012704]; Department of Energy, Office of Biological and Environmental Research [PS005]; German Academic Exchange Service (Deutscher Akademischer Austauschdienst, DAAD) Bonn FX This manuscript has been co-authored by employees of Brookhaven Science Associates, LLC under Contract DE-SC0012704 with the U. S. Department of Energy, Office of Biological and Environmental Research within the Office of Science. Additional support was provided by a Mesoscale Pilot project (PS005) from the Department of Energy, Office of Biological and Environmental Research, as well as the German Academic Exchange Service (Deutscher Akademischer Austauschdienst, DAAD) Bonn, which supported an internship for Carina Weber and Alex Nauth. We also thank Richard Ferrieri for advices and encouragement, as well as Youwen Xu and Colleen Shea for technical and manuscript edit assistance. NR 34 TC 2 Z9 2 U1 2 U2 8 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-0520 EI 1477-0539 J9 ORG BIOMOL CHEM JI Org. Biomol. Chem. PY 2015 VL 13 IS 46 BP 11235 EP 11243 DI 10.1039/c5ob01654a PG 9 WC Chemistry, Organic SC Chemistry GA CW9GQ UT WOS:000365307400009 PM 26411301 ER PT B AU Cornell, L Johnson, N Shapiro, GI AF Cornell, Liam Johnson, Neil Shapiro, Geoffrey I. BE Curtin, NJ Sharma, RA TI Disruption of DNA Repair by Cell Cycle and Transcriptional CDK Inhibition SO PARP INHIBITORS FOR CANCER THERAPY SE Cancer Drug Discovery and Development LA English DT Article; Book Chapter DE Cyclin dependent kinase; CDK; Cyclin; Cell cycle; Homologous recombination; PARP; BRCA; DNA repair; DSB ID DEPENDENT KINASE INHIBITOR; FLAVOPIRIDOL-INDUCED APOPTOSIS; HUMAN TUMOR XENOGRAFTS; RNA-POLYMERASE-II; END RESECTION; HOMOLOGOUS RECOMBINATION; RETINOBLASTOMA PROTEIN; ANTITUMOR-ACTIVITY; DAMAGE RESPONSE; PHASE-I AB The eukaryotic cell cycle is a tightly regulated series of events coordinated by the periodic activation of members of the cyclin dependent kinases (CDK) family. In addition, a subset of CDK family members play critical roles in transcriptional regulation. Dysregulation of CDK activity by a variety of genetic and epigenetic mechanisms is universally observed in cancer and is thought to be a primary driving force in carcinogenesis, such that there has been longstanding interest in targeting CDKs for cancer therapy. Along with orchestrating the cell cycle and transcriptional events, CDKs have also been directly implicated in the DNA damage response. CDK activity governs cell cycle phase and thus indirectly affects double strand break (DSB) repair pathway choice. Recent evidence also directly implicates CDKs 1 and 2 in homologous recombination DNA repair (HRR) since their activities are crucial at early stages of the repair pathway. These findings suggest that CDK inhibition may not only address aberrant cell proliferation, but may also sensitize cells to a variety of DNA damaging agents as well as PARP inhibition. C1 [Cornell, Liam; Shapiro, Geoffrey I.] Dana Farber Canc Inst, Early Drug Dev Ctr, Boston, MA 02115 USA. [Cornell, Liam; Shapiro, Geoffrey I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Johnson, Neil] Fox Chase Canc Ctr, Dev Therapeut Program, Philadelphia, PA 19111 USA. RP Cornell, L (reprint author), Dana Farber Canc Inst, Early Drug Dev Ctr, Boston, MA 02115 USA. EM Liam_Cornell@DFCI.HARVARD.EDU; Neil.Johnson@fccc.edu; geoffrey_shapiro@dfci.harvard.edu NR 95 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-3-319-14151-0; 978-3-319-14150-3 J9 CANCER DRUG DISCOV D JI Canc. Drug. Disc. Dev. PY 2015 VL 83 BP 413 EP 430 DI 10.1007/978-3-319-14151-0_17 D2 10.1007/978-3-319-14151-0 PG 18 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy GA BD9UZ UT WOS:000365493100018 ER PT J AU Sorgun, MH Aksun, Z Atalay, YB Yucesan, C AF Sorgun, Mine Hayriye Aksun, Zerin Atalay, Yahya Burak Yucesan, Canan TI Restless legs syndrome in multiple sclerosis SO TURKISH JOURNAL OF MEDICAL SCIENCES LA English DT Article DE Multiple sclerosis; restless legs syndrome; EDSS ID HIGH PREVALENCE; RISK-FACTORS; PET; RLS; MULTICENTER; POPULATION; DOPAMINE; DISORDER; TURKEY AB Background/aim: There have been conflicting results in the literature regarding the relationship between functional system involvement, the expanded disability status scale (EDSS), and the presence of restless legs syndrome (RLS) in patients with multiple sclerosis (MS). Materials and methods: Ninety-one patients with MS and 40 patients in a control group (headache, essential tremor, and benign positional paroxysmal vertigo) were studied. The patients underwent a complete neurological examination and Kurtzke functional system scores were calculated. In order to assess the temporal relation between the onset of RLS and MS, a semistructured interview guided by a questionnaire about RLS was applied to all of the patients. Results: Sixteen (17.6%) of the patients with MS and 1 (2.5%) patient in the control group had RLS. The prevalence of RLS was higher in patients with MS, compared to the control group (P = 0.018). Among the patients with MS, none of them suffered from RLS before the onset of MS, whereas sixteen patients (16%) suffered RLS after the onset of MS. There was no significant relationship between functional system involvement and the presence of RLS. Conclusion: The prevalence of RLS was higher in MS patients than it was in the control group. No association was found between RLS and functional system involvement in MS patients. C1 [Sorgun, Mine Hayriye; Aksun, Zerin; Yucesan, Canan] Ankara Univ, Fac Med, Dept Neurol, Ibni Sina Hosp, TR-06100 Ankara, Turkey. [Atalay, Yahya Burak] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Sorgun, MH (reprint author), Ankara Univ, Fac Med, Dept Neurol, Ibni Sina Hosp, TR-06100 Ankara, Turkey. EM drmsorgun79@yahoo.com.tr NR 33 TC 0 Z9 0 U1 0 U2 1 PU TUBITAK SCIENTIFIC & TECHNICAL RESEARCH COUNCIL TURKEY PI ANKARA PA ATATURK BULVARI NO 221, KAVAKLIDERE, ANKARA, 00000, TURKEY SN 1300-0144 EI 1303-6165 J9 TURK J MED SCI JI Turk. J. Med. Sci. PY 2015 VL 45 IS 6 BP 1268 EP 1273 DI 10.3906/sag-1401-19 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA CX2FD UT WOS:000365510300013 PM 26775381 ER PT S AU Senderovich, A Weidlich, M Gal, A Mandelbaum, A Kadish, S Bunnell, CA AF Senderovich, Arik Weidlich, Matthias Gal, Avigdor Mandelbaum, Avishai Kadish, Sarah Bunnell, Craig A. BE Zdravkovic, J Kirikova, M Johannesson, P TI Discovery and Validation of Queueing Networks in Scheduled Processes SO ADVANCED INFORMATION SYSTEMS ENGINEERING, CAISE 2015 SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 27th International Conference on Advanced Information Systems Engineering (CAiSE) CY JUN 08-12, 2015 CL Stockholm, SWEDEN ID CONFORMANCE CHECKING; EQUIVALENCE; BLOCKING; WORKFLOW AB Service processes, for example in transportation, telecommunications or the health sector, are the backbone of today's economies. Conceptual models of such service processes enable operational analysis that supports, e.g., resource provisioning or delay prediction. Automatic mining of such operational models becomes feasible in the presence of event-data traces. In this work, we target the mining of models that assume a resource-driven perspective and focus on queueing effects. We propose a solution for the discovery and validation problem of scheduled service processes - processes with a predefined schedule for the execution of activities. Our prime example for such processes are complex outpatient treatments that follow prior appointments. Given a process schedule and data recorded during process execution, we show how to discover Fork/Join networks, a specific class of queueing networks, and how to assess their operational validity. We evaluate our approach with a real-world dataset comprising clinical pathways of outpatient clinics, recorded by a real-time location system (RTLS). We demonstrate the value of the approach by identifying and explaining operational bottlenecks. C1 [Senderovich, Arik; Gal, Avigdor; Mandelbaum, Avishai] Technion Israel Inst Technol, Haifa, Israel. [Weidlich, Matthias] Univ London Imperial Coll Sci Technol & Med, London, England. [Kadish, Sarah; Bunnell, Craig A.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Weidlich, M (reprint author), Univ London Imperial Coll Sci Technol & Med, London, England. EM sariks@tx.technion.ac.il; m.weidlich@imperial.ac.uk; avigal@ie.technion.ac.il; avim@ie.technion.ac.il; sarah_kadish@dfci.harvard.edu; craig_bunnell@dfci.harvard.edu NR 35 TC 1 Z9 1 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-319-19069-3; 978-3-319-19068-6 J9 LECT NOTES COMPUT SC PY 2015 VL 9097 BP 417 EP 433 DI 10.1007/978-3-319-19069-3_26 PG 17 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Computer Science, Software Engineering; Computer Science, Theory & Methods SC Computer Science GA BD9NZ UT WOS:000364990400029 ER PT J AU Fang, JL Wang, DH Zhao, Q Hong, Y Jin, YL Liu, ZS Zhou, KH Jing, XH Yu, XC Pan, RQ Chang, A Liu, HS Zhu, B AF Fang, Jiliang Wang, Danhong Zhao, Qing Hong, Yang Jin, Yulian Liu, Zhishun Zhou, Kehua Jing, Xianghong Yu, Xiaochun Pan, Ruiqi Chang, Andrew Liu, Hesheng Zhu, Bing TI Brain-Gut Axis Modulation of Acupuncture in Functional Dyspepsia: A Preliminary Resting-State fcMRI Study SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Article ID CONNECTIVITY; MOTION; TRANSLATION; VALIDATION; DISORDERS; IMPACT; TRIAL; SCALE; INDEX; MRI AB Objective. To explore acupuncture effects on brain functional connectivity in patients with functional dyspepsia (FD). Methods. Eight patients in an acupuncture treatment group and ten healthy adults in the control group participated in the study. Acupuncture effectiveness was evaluated based on changes of the gastrointestinal symptoms, gastric motility measurements, and gastrin levels and comparisons with the control group when appropriate. To investigate functional connectivity changes related to FD and potential modulation after acupuncture, a set of regions of interest (ROIs) were selected according to previous fMRI reports of acupuncture. Results. Patients showed significant improvements of FD signs and symptoms after acupuncture treatments. For all of the ROIs, we identified subportions of the networks showing reduced connectivity in patients with FD. Connectivity between the ROIs and corresponding disease targets showed significant improvement after acupuncture treatment (P < 0.05) in all ROIs except for right medial temporal lobe-hippocampus and right inferior parietal lobule. Conclusion. Functional connectivity of the brain is changed in patients with FD but approximates that in healthy control after acupuncture treatment. The relief of gastrointestinal signs and symptoms by acupuncture is likely due to the normalization of brain-gut axis associated with FD. C1 [Fang, Jiliang; Zhao, Qing; Hong, Yang] China Acad Chinese Med Sci, Guang An Men Hosp, Dept Radiol, Beijing 100053, Peoples R China. [Wang, Danhong; Pan, Ruiqi; Liu, Hesheng] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr, Charlestown, MA 02129 USA. [Jin, Yulian; Liu, Zhishun] China Acad Chinese Med Sci, Guang An Men Hosp, Dept Acupuncture & Moxibust, Beijing 100053, Peoples R China. [Zhou, Kehua] Daemen Coll, Dept Hlth Care Studies, Amherst, NY 14226 USA. [Jing, Xianghong; Yu, Xiaochun] China Acad Chinese Med Sci, Inst Acupuncture & Moxibust, Beijing 100700, Peoples R China. [Chang, Andrew] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. RP Liu, HS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr, Charlestown, MA 02129 USA. EM hesheng@nmr.mgh.harvard.edu; zhubing@mail.cintcm.ac.cn OI Zhou, Kehua/0000-0002-2844-1604 FU State Key Development Program for Basic Research of China (973) [2011CB505202]; National Natural Science Foundation of China [30870668, 81273674] FX This study was funded by the State Key Development Program for Basic Research of China (973, Grant 2011CB505202) and the National Natural Science Foundation of China (Grant 30870668 and Grant 81273674). NR 38 TC 0 Z9 0 U1 3 U2 8 PU HINDAWI PUBLISHING CORP 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 2015 AR 860463 DI 10.1155/2015/860463 PG 11 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA CW7RT UT WOS:000365197500001 ER PT S AU Rasmusson, AM Irvine, JM AF Rasmusson, Ann M. Irvine, John M. BE Schmorrow, DD Fidopiastis, CM TI The Neurobiology of Executive Function Under Stress and Optimization of Performance SO FOUNDATIONS OF AUGMENTED COGNITION, AC 2015 SE Lecture Notes in Artificial Intelligence LA English DT Proceedings Paper CT 9th International Conference on Augmented Cognition (AC) Held as Part of 17th International Conference on Human-Computer Interaction (HCI International) CY AUG 02-07, 2015 CL Los Angeles, CA DE Resilience; PTSD; Translational neuroscience; Neuropeptide Y; Allopregnanolone; Neuroactive steroids; Predictive algorithms; Functional data analysis; Non-linear modeling; Machine learning ID PLASMA NEUROPEPTIDE-Y; NEUROSTEROID BIOSYNTHESIS; DEHYDROEPIANDROSTERONE-SULFATE; OBJECTIVE PERFORMANCE; METABOLIC SYNDROME; TRAUMA EXPOSURE; BASE-LINE; DISORDER; HUMANS; ALLOPREGNANOLONE AB Much basic and clinical research to date has investigated predictors of stress resilience and vulnerability, indicating, for example, that broad impact neurobiological factors, such as neuropeptide Y (NPY) and neuroactive steroids, are mechanistically related to short term stress resilience, as well as longterm patterns of stress-related medical and neuropsychiatric comorbidities. The problem is that we lack good methods for identifying predictors of stress resilience or vulnerability at an individual level, so that human performance and therapeutic interventions can be targeted precisely to underlying points of malfunction for maximum effectiveness. We thus propose modified experimental designs that capitalize on our growing capacities to query and analyze multimodal data across the translational levels of human biology and behavior. We propose that use of these methods in studies of individuals participating in intense military training or returning from deployment could enable better prediction of performance, and development of more effective personalized interventions aimed at optimizing and maintaining stress resilience over time. C1 [Rasmusson, Ann M.] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Rasmusson, Ann M.] Boston Univ, Boston, MA 02215 USA. [Irvine, John M.] Draper Lab, Cambridge, MA USA. RP Rasmusson, AM (reprint author), VA Boston Healthcare Syst, Boston, MA 02130 USA. EM ann.rasmusson@gmail.com; jirvine@draper.com NR 52 TC 0 Z9 0 U1 2 U2 5 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-319-20816-9; 978-3-319-20815-2 J9 LECT NOTES ARTIF INT PY 2015 VL 9183 BP 112 EP 123 DI 10.1007/978-3-319-20816-9_12 PG 12 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems SC Computer Science GA BD9KA UT WOS:000364809400012 ER PT J AU Tai, YT Anderson, KC AF Tai, Yu-Tzu Anderson, Kenneth C. TI Targeting B-cell maturation antigen in multiple myeloma SO IMMUNOTHERAPY LA English DT Review DE ADC; antibody drug conjugate; B-cell maturation antigen; BCMA; BM; bone marrow; CAR-expressing T cells; CAR-T; chimeric antigen receptor; Fc-engineered therapeutic antibody; microenvironment; MM; targeted immunotherapy; multiple myeloma ID NATURAL-KILLER-CELL; ANTIBODY-DRUG-CONJUGATE; MALIGNANT PLASMA-CELLS; BONE-MARROW; IN-VITRO; T-CELLS; POTENTIAL TREATMENT; ANTITUMOR-ACTIVITY; ACTIVATING FACTOR; KIR ANTIBODY AB Novel effective immunotherapies are needed for patients with multiple myeloma (MM), since disease recurrence remains a major obstacle. B-cell maturation antigen (BCMA), a cell surface protein universally expressed on malignant plasma cells, has emerged as a very selective antigen to be targeted in novel treatments for MM. We here first review BCMA-related biology, and then highlight the recent clinical development of a novel afucosylated anti-BCMA monoclonal antibody conjugated with monomethyl auristatin F via noncleavable linker (GSK2857916). Chimeric antigen receptor-expressing T cells targeting BCMA may also induce specific and durable anti-MM responses by patients' own effector cells. C1 [Tai, Yu-Tzu; Anderson, Kenneth C.] Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol,Dana Farber Canc Inst, Boston, MA 02215 USA. RP Tai, YT (reprint author), Harvard Univ, Sch Med, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol,Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM yu-tzu_tai@dfci.harvard.edu FU NIH [RO1050947, PO1-CA078378]; DF/HCC SPORE in Multiple Myeloma [P50CA100707] FX Y-T Tai is a consultant for Onyx. KC Anderson serves on advisory boards to Onyx, Celgene, Gilead, Bristol-Myers Squibb and Sanofi-Aventis and is a scientific founder of Acetylon and Oncopep. Funding: NIH grants RO1050947, PO1-CA078378 and DF/HCC SPORE in Multiple Myeloma P50CA100707; KC Anderson is an American Cancer Society Clinical Research Professor. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 75 TC 8 Z9 8 U1 4 U2 9 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1750-743X EI 1750-7448 J9 IMMUNOTHERAPY-UK JI Immunotherapy PY 2015 VL 7 IS 11 BP 1187 EP 1199 DI 10.2217/imt.15.77 PG 13 WC Immunology SC Immunology GA CW7HR UT WOS:000365169400008 PM 26370838 ER PT J AU Manchikanti, L Hirsch, JA AF Manchikanti, Laxmaiah Hirsch, Joshua A. TI Comments on a systematic review and meta-analysis of steroids for epidural injections in spinal stenosis SO DRUG DESIGN DEVELOPMENT AND THERAPY LA English DT Letter ID CHRONIC LOW-BACK; RANDOMIZED-TRIAL; DOUBLE-BLIND; PAIN C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY 42003 USA. [Manchikanti, Laxmaiah] Univ Louisville, Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Intervent Care, Minimally Invas Spine Surg, Intervent Radiol,NeuroIntervent Serv, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Neuroendovasc Program, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Manchikanti, L (reprint author), Pain Management Ctr Paducah, Med, 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 10 TC 0 Z9 0 U1 1 U2 1 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 2015 VL 9 BP 2721 EP 2722 DI 10.2147/DDDT.S86080 PG 2 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CI5HH UT WOS:000354785200001 ER PT J AU Manchikanti, L Hirsch, JA AF Manchikanti, Laxmaiah Hirsch, Joshua A. TI Comments on a systematic review and meta-analysis of steroids for epidural injections in spinal stenosis SO DRUG DESIGN DEVELOPMENT AND THERAPY LA English DT Letter ID CHRONIC LOW-BACK; RANDOMIZED-TRIAL; DOUBLE-BLIND; PAIN C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY 42003 USA. [Manchikanti, Laxmaiah] Univ Louisville, Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Intervent Care, Minimally Invas Spine Surg, NeuroIntervent Serv,Intervent Radiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Neuroendovasc Program, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Manchikanti, L (reprint author), Pain Management Ctr Paducah, 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 10 TC 0 Z9 0 U1 2 U2 2 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 2015 VL 9 BP 2721 EP 2722 DI 10.2147/DDDT.S86080 PG 2 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CW4RC UT WOS:000364978200001 ER PT J AU Gardiner, C Harrison, P Belting, M Boing, A Campello, E Carter, BS Collier, ME Coumans, F Ettelaie, C van Es, N Hochberg, FH Mackman, N Rennert, RC Thaler, J Rak, J Nieuwland, R AF Gardiner, Chris Harrison, Paul Belting, Mattias Boing, Anita Campello, Elena Carter, Bob S. Collier, Mary E. Coumans, Frank Ettelaie, Camille van Es, Nick Hochberg, Fred H. Mackman, Nigel Rennert, Robert C. Thaler, Johannes Rak, Janusz Nieuwland, Rienk TI Extracellular vesicles, tissue factor, cancer and thrombosis - discussion themes of the ISEV 2014 Educational Day SO JOURNAL OF EXTRACELLULAR VESICLES LA English DT Review DE extracellular vesicles; thrombosis; cancer; tissue factor ID FACTOR-POSITIVE MICROPARTICLES; FACTOR-BEARING MICROPARTICLES; FACTOR PROCOAGULANT ACTIVITY; CELL-DERIVED MICROPARTICLES; GROWTH-FACTOR RECEPTOR; CYTOPLASMIC DOMAIN; ENDOTHELIAL-CELLS; COAGULATION ACTIVATION; VENOUS THROMBOEMBOLISM; TUMOR PROGRESSION AB Although the association between cancer and venous thromboembolism (VTE) has long been known, the mechanisms are poorly understood. Circulating tissue factor-bearing extracellular vesicles have been proposed as a possible explanation for the increased risk of VTE observed in some types of cancer. The International Society for Extracellular Vesicles (ISEV) and International Society on Thrombosis and Haemostasis (ISTH) held a joint Educational Day in April 2014 to discuss the latest developments in this field. This review discusses the themes of that event and the ISEV 2014 meeting that followed. C1 [Gardiner, Chris] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Obstet & Gynaecol, Womens Ctr, Oxford OX3 9DU, England. [Harrison, Paul] Univ Birmingham, Sch Med, Sch Immun & Infect, Birmingham, W Midlands, England. [Belting, Mattias] Skane Univ Hosp, Dept Pathol & Oncol, Clin Sci, Lund, Sweden. [Boing, Anita; Coumans, Frank; Nieuwland, Rienk] Univ Amsterdam, Acad Med Ctr, Dept Clin Chem, NL-1105 AZ Amsterdam, Netherlands. [Campello, Elena] Univ Padua, Sch Med, Dept Cardiol Thorac & Vasc Sci, Padua, Italy. [Carter, Bob S.; Hochberg, Fred H.; Rennert, Robert C.] Univ Calif San Diego, Div Neurosurg, La Jolla, CA 92093 USA. [Collier, Mary E.] Univ Leicester, Dept Cardiovasc Sci, Clin Sci Wing, Glenfield Gen Hosp, Leicester, Leics, England. [Coumans, Frank] Univ Amsterdam, Acad Med Ctr, Dept Biomed Engn & Phys, NL-1105 AZ Amsterdam, Netherlands. [Ettelaie, Camille] Univ Hull, Sch Biol Biomed & Environm Sci, Kingston Upon Hull HU6 7RX, N Humberside, England. [van Es, Nick] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Hochberg, Fred H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hochberg, Fred H.] Massachusetts Gen Hosp, Program Neurosci, Boston, MA 02114 USA. [Hochberg, Fred H.] Harvard Univ, Sch Med, Boston, MA USA. [Mackman, Nigel] Univ N Carolina, Dept Med, Thrombosis & Hemostasis Program, UNC McAllister Heart Inst, Chapel Hill, NC USA. [Thaler, Johannes] Med Univ Vienna, Clin Div Haematol & Haemostaseol, Dept Med 1, Vienna, Austria. [Rak, Janusz] McGill Univ, Montreal Childrens Hosp, Dept Pediat, Res Inst MUHC, Montreal, PQ H3H 1P3, Canada. RP Gardiner, C (reprint author), Univ Oxford, John Radcliffe Hosp, Nuffield Dept Obstet & Gynaecol, Womens Ctr, Level 3, Oxford OX3 9DU, England. EM chris.gardiner@obs-gyn.ox.ac.uk OI Harrison, Paul/0000-0003-4610-8909 FU Medical Research Council [MR/J003360/1]; NCATS NIH HHS [UH2 TR000931] NR 129 TC 14 Z9 14 U1 1 U2 7 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2001-3078 J9 J EXTRACELL VESICLES JI J. Extracell. Vesicles PY 2015 VL 4 AR UNSP 26901 DI 10.3402/jev.v4.26901 PG 14 WC Cell Biology SC Cell Biology GA CW5YF UT WOS:000365072500001 PM 25773446 ER PT J AU Kholia, S Jorfi, S Thompson, PR Causey, CP Nicholas, AP Inal, JM Lange, S AF Kholia, Sharad Jorfi, Samireh Thompson, Paul R. Causey, Corey P. Nicholas, Anthony P. Inal, Jameel M. Lange, Sigrun TI A novel role for peptidylarginine deiminases in microvesicle release reveals therapeutic potential of PAD inhibition in sensitizing prostate cancer cells to chemotherapy SO JOURNAL OF EXTRACELLULAR VESICLES LA English DT Article DE peptidylarginine deiminases; chloramidine; microvesicles; microvesiculation; prostate cancer cells (PC3) ID NUCLEOSIDE DIPHOSPHATE KINASE; RHEUMATOID-ARTHRITIS; IN-VITRO; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; CIRCULATING MICROPARTICLES; PLATELET MICROPARTICLES; MEMBRANE MICROPARTICLES; CITRULLINATED EPITOPES; ARGININE METHYLATION; HISTONE DEIMINATION AB Introduction: Protein deimination, defined as the post-translational conversion of protein-bound arginine to citrulline, is carried out by a family of 5 calcium-dependent enzymes, the peptidylarginine deiminases (PADs) and has been linked to various cancers. Cellular microvesicle (MV) release, which is involved in cancer progression, and deimination have not been associated before. We hypothesize that elevated PAD expression, observed in cancers, causes increased MV release in cancer cells and contributes to cancer progression. Background: We have previously reported that inhibition of MV release sensitizes cancer cells to chemotherapeutic drugs. PAD2 and PAD4, the isozymes expressed in patients with malignant tumours, can be inhibited with the pan-PAD-inhibitor chloramidine (Cl-am). We sought to investigate whether Cl-am can inhibit MV release and whether this pathway could be utilized to further increase the sensitivity of cancer cells to drug-directed treatment. Methods: Prostate cancer cells (PC3) were induced to release high levels of MVs upon BzATP stimulation of P2X(7) receptors. Western blotting with the pan-protein deimination antibody F95 was used to detect a range of deiminated proteins in cells stimulated to microvesiculate. Changes in deiminated proteins during microvesiculation were revealed by immunoprecipitation and immunoblotting, and mass spectrometry identified deiminated target proteins with putative roles in microvesiculation. Conclusion: We report for the first time a novel function of PADs in the biogenesis of MVs in cancer cells. Our results reveal that during the stimulation of prostate cancer cells (PC3) to microvesiculate, PAD2 and PAD4 expression levels and the deimination of cytoskeletal actin are increased. Pharmacological inhibition of PAD enzyme activity using Cl-am significantly reduced MV release and abrogated the deimination of cytoskeletal actin. We demonstrated that combined Cl-am and methotrexate (MTX) treatment of prostate cancer cells increased the cytotoxic effect of MTX synergistically. Refined PAD inhibitors may form part of a novel combination therapy in cancer treatment. C1 [Kholia, Sharad; Jorfi, Samireh; Inal, Jameel M.] London Metropolitan Univ, Sch Human Sci, Cellular & Mol Immunol Res Ctr, London N7 8DB, England. [Thompson, Paul R.] Scripps Res Inst, Dept Chem, Jupiter, FL USA. [Causey, Corey P.] Univ N Florida, Dept Chem, Jacksonville, FL USA. [Nicholas, Anthony P.] Univ Alabama Birmingham, Dept Neurol, Birmingham, VA USA. [Nicholas, Anthony P.] Birmingham VA Med Ctr, Birmingham, AL USA. [Lange, Sigrun] UCL, Sch Pharm, London WC1N 1AX, England. RP Inal, JM (reprint author), London Metropolitan Univ, Sch Hlth Sci, Cellular & Mol Immunol Res Ctr, 166-220 Holloway Rd, London N7 8DB, England. EM j.inal@londonmet.ac.uk; sigrun.lange@ucl.ac.uk RI Inal, Jameel/G-2995-2010 OI Inal, Jameel/0000-0002-7200-0363 FU NCI NIH HHS [P30 CA013148]; NIGMS NIH HHS [R01 GM079357] NR 78 TC 4 Z9 4 U1 2 U2 5 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2001-3078 J9 J EXTRACELL VESICLES JI J. Extracell. Vesicles PY 2015 VL 4 AR UNSP 26192 DI 10.3402/jev.v4.26192 PG 16 WC Cell Biology SC Cell Biology GA CW5YP UT WOS:000365073500001 PM 26095379 ER PT J AU Laurent, LC Abdel-Mageed, AB Adelson, PD Arango, J Balaj, L Breakefield, X Carlson, E Carter, BS Majem, B Chen, CC Cocucci, E Danielson, K Courtright, A Das, S Abd Elmageed, ZY Enderle, D Ezrin, A Ferrer, M Freedman, J Galas, D Gandhi, R Huentelman, MJ Van Keuren-Jensen, K Kalani, Y Kim, Y Krichevsky, AM Lai, C Lal-Nag, M Laurent, CD Leonardo, T Li, F Malenica, I Mondal, D Nejad, P Patel, T Raffai, RL Rubio, R Skog, J Spetzler, R Sun, J Tanriverdi, K Vickers, K Wang, L Wang, YY Wei, ZY Weiner, HL Wong, D Yan, IK Yeri, A Gould, S AF Laurent, Louise C. Abdel-Mageed, Asim B. Adelson, P. David Arango, Jorge Balaj, Leonora Breakefield, Xandra Carlson, Elizabeth Carter, Bob S. Majem, Blanca Chen, Clark C. Cocucci, Emanuele Danielson, Kirsty Courtright, Amanda Das, Saumya Abd Elmageed, Zakaria Y. Enderle, Daniel Ezrin, Alan Ferrer, Marc Freedman, Jane Galas, David Gandhi, Roopali Huentelman, Matthew J. Van Keuren-Jensen, Kendall Kalani, Yashar Kim, Yong Krichevsky, Anna M. Lai, Charles Lal-Nag, Madhu Laurent, Clara D. Leonardo, Trevor Li, Feng Malenica, Ivana Mondal, Debasis Nejad, Parham Patel, Tushar Raffai, Robert L. Rubio, Renee Skog, Johan Spetzler, Robert Sun, Jie Tanriverdi, Kahraman Vickers, Kasey Wang, Liang Wang, Yaoyu Wei, Zhiyun Weiner, Howard L. Wong, David Yan, Irene K. Yeri, Ashish Gould, Stephen TI Meeting report: discussions and preliminary findings on extracellular RNA measurement methods from laboratories in the NIH Extracellular RNA Communication Consortium SO JOURNAL OF EXTRACELLULAR VESICLES LA English DT Article DE extracellular RNA; extracellular vesicles; exosomes; microvesicles; RNA sequencing ID HIGH-DENSITY-LIPOPROTEINS; PROSTATE-CANCER; BREAST-CANCER; CIRCULATING MICRORNAS; POLYETHYLENE-GLYCOL; CEREBROSPINAL-FLUID; SEQUENCING METHODS; EXOSOME ISOLATION; GENE-EXPRESSION; RECIPIENT CELLS AB Extracellular RNAs (exRNAs) have been identified in all tested biofluids and have been associated with a variety of extracellular vesicles, ribonucleoprotein complexes and lipoprotein complexes. Much of the interest in exRNAs lies in the fact that they may serve as signalling molecules between cells, their potential to serve as biomarkers for prediction and diagnosis of disease and the possibility that exRNAs or the extracellular particles that carry them might be used for therapeutic purposes. Among the most significant bottlenecks to progress in this field is the lack of robust and standardized methods for collection and processing of biofluids, separation of different types of exRNA-containing particles and isolation and analysis of exRNAs. The Sample and Assay Standards Working Group of the Extracellular RNA Communication Consortium is a group of laboratories funded by the U.S. National Institutes of Health to develop such methods. In our first joint endeavour, we held a series of conference calls and in-person meetings to survey the methods used among our members, placed them in the context of the current literature and used our findings to identify areas in which the identification of robust methodologies would promote rapid advancements in the exRNA field. C1 [Laurent, Louise C.] Univ Calif San Diego, Dept Reprod Med, Div Maternal Fetal Med, San Diego, CA 92103 USA. [Laurent, Louise C.] Sanford Consortium Regenerat Med,San Diego, San Diego, CA USA. [Abdel-Mageed, Asim B.; Abd Elmageed, Zakaria Y.] Tulane Univ, Sch Med, Dept Urol, New Orleans, LA 70112 USA. [Adelson, P. David; Arango, Jorge] Phoenix Childrens Hosp, Phoenix, AZ USA. [Balaj, Leonora; Breakefield, Xandra; Lai, Charles] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Balaj, Leonora; Breakefield, Xandra; Lai, Charles] Harvard Univ, Sch Med, Program Neurosci, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Breakefield, Xandra] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Carlson, Elizabeth; Courtright, Amanda; Van Keuren-Jensen, Kendall; Malenica, Ivana; Yeri, Ashish] Translat Genom Res Inst, Neurogen Div, Phoenix, AZ USA. [Carter, Bob S.; Chen, Clark C.] Univ Calif San Diego, Div Neurosurg, Ctr Theoret & Appl Neurooncol, San Diego, CA 92103 USA. [Majem, Blanca; Kim, Yong; Li, Feng; Sun, Jie; Wong, David] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. [Cocucci, Emanuele] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Danielson, Kirsty; Das, Saumya; Laurent, Clara D.; Leonardo, Trevor] Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA. [Enderle, Daniel] Exosome Diagnost GmbH, Martinsried, Germany. [Ezrin, Alan] NXPharmaGen, Miami, FL USA. [Ferrer, Marc; Lal-Nag, Madhu] NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci NCATS, Bethesda, MD 20892 USA. [Freedman, Jane; Tanriverdi, Kahraman] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. [Galas, David] Pacific Northwest Diabet Res Inst, Seattle, WA USA. [Galas, David] Univ Luxembourg, Luxembourg Ctr Syst Biomed, Esch Sur Alzette, Luxembourg. [Gandhi, Roopali; Nejad, Parham; Weiner, Howard L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol,Ctr Neurol Dis, Boston, MA 02115 USA. [Huentelman, Matthew J.] TGen, Phoenix, AZ USA. [Kalani, Yashar; Raffai, Robert L.] Barrow Neurol Inst, Phoenix, AZ USA. [Krichevsky, Anna M.; Wei, Zhiyun] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Mondal, Debasis] Tulane Univ, Sch Med, Dept Pharmacol, New Orleans, LA 70112 USA. [Patel, Tushar] Mayo Clin Florida, Dept Transplantat, Jacksonville, FL USA. [Patel, Tushar; Yan, Irene K.] Mayo Clin Florida, Dept Canc Biol, Jacksonville, FL USA. [Spetzler, Robert] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Spetzler, Robert] Dept Vet Affairs, San Francisco, CA USA. [Rubio, Renee; Wang, Yaoyu] Dana Farber Canc Inst, Ctr Canc Computat Biol, Boston, MA 02115 USA. [Skog, Johan] Exosome Diagnost, Cambridge, MA USA. [Vickers, Kasey] Vanderbilt Univ, Med Ctr, Dept Mol Physiol & Biophys, Nashville, TN USA. [Vickers, Kasey] Vanderbilt Univ, Med Ctr, Dept Med, Div Cardiovasc Med, Nashville, TN USA. [Wang, Liang] Med Coll Wisconsin, Dept Pathol, Milwaukee, WI 53226 USA. [Gould, Stephen] Johns Hopkins Univ, Dept Biol Chem, Baltimore, MD USA. RP Laurent, LC (reprint author), Univ Calif San Diego, Sanford Consortium Regenerat Med, 2880 Torrey Pines Scen Dr, La Jolla, CA 92093 USA. EM llaurent@ucsd.edu FU NCATS NIH HHS [UH2 TR000931, UH2 TR000884, UH2 TR000890, UH2 TR000891, UH2 TR000901, UH2 TR000906, UH2 TR000921, UH2 TR000923, UH2 TR000928, UH3 TR000884, UH3 TR000901, UH3 TR000923, UH3 TR000931]; NCI NIH HHS [P01 CA069246, U19 CA179512, U19 CA179514, U19 CA179563]; NHLBI NIH HHS [P01 HL116263, R01 HL128996, U01 HL126494, U01 HL126496]; NIDA NIH HHS [U54 DA036134] NR 100 TC 11 Z9 11 U1 3 U2 8 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2001-3078 J9 J EXTRACELL VESICLES JI J. Extracell. Vesicles PY 2015 VL 4 SI SI AR 26533 DI 10.3402/jev.v4.26533 PG 18 WC Cell Biology SC Cell Biology GA CW5ZW UT WOS:000365077100001 PM 26320937 ER PT J AU Patton, JG Franklin, JL Weaver, AM Vickers, K Zhang, B Coffey, RJ Ansel, M Blelloch, R Goga, A Huang, B L'Etoille, N Raffai, RL Lai, CP Krichevsky, AM Mateescu, B Greiner, VJ Hunter, C Voinnet, O McManus, MT AF Patton, James G. Franklin, Jeffrey L. Weaver, Alissa M. Vickers, Kasey Zhang, Bing Coffey, Robert J. Ansel, Mark Blelloch, Robert Goga, Andrei Huang, Bo L'Etoille, Noelle Raffai, Robert L. Lai, Charles P. Krichevsky, Anna M. Mateescu, Bogdan Greiner, Vanille J. Hunter, Craig Voinnet, Olivier McManus, Michael T. TI Biogenesis, delivery, and function of extracellular RNA SO JOURNAL OF EXTRACELLULAR VESICLES LA English DT Article DE ERCC; exRNA; extracellular RNA ID BREAST-CANCER CELLS; TOLL-LIKE RECEPTORS; MESSENGER-RNAS; MULTIVESICULAR ENDOSOMES; ANTIVIRAL IMMUNITY; COLORECTAL-CANCER; ENDOTHELIAL-CELLS; T-CELLS; EXOSOMES; MICRORNA AB The Extracellular RNA (exRNA) Communication Consortium was launched by the National Institutes of Health to focus on the extent to which RNA might function in a non-cell-autonomous manner. With the availability of increasingly sensitive tools, small amounts of RNA can be detected in serum, plasma, and other bodily fluids. The exact mechanism(s) by which RNA can be secreted from cells and the mechanisms for the delivery and uptake by recipient cells remain to be determined. This review will summarize current knowledge about the biogenesis and delivery of exRNA and outline projects seeking to understand the functional impact of exRNA. C1 [Patton, James G.] Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37235 USA. [Franklin, Jeffrey L.; Weaver, Alissa M.; Coffey, Robert J.] VA Med Ctr, Nashville, TN USA. [Franklin, Jeffrey L.; Coffey, Robert J.] Vanderbilt Univ, Dept Cell & Dev Biol, Nashville, TN 37235 USA. [Franklin, Jeffrey L.; Coffey, Robert J.] Vanderbilt Univ, Dept Med, Nashville, TN 37235 USA. [Weaver, Alissa M.] Vanderbilt Univ, Dept Canc Biol, Nashville, TN 37235 USA. [Vickers, Kasey] Vanderbilt Univ, Dept Cardiol, Nashville, TN 37235 USA. [Zhang, Bing] Vanderbilt Univ, Dept Biomed Informat, Nashville, TN 37235 USA. [Ansel, Mark; Greiner, Vanille J.] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. [Ansel, Mark] Univ Calif San Francisco, Sandler Asthma Basic Res Ctr, San Francisco, CA 94143 USA. [Blelloch, Robert] Univ Calif San Francisco, Dept Urol, San Francisco, CA USA. [Blelloch, Robert] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA. [Goga, Andrei; L'Etoille, Noelle] Univ Calif San Francisco, Dept Cell & Tissue Biol, San Francisco, CA 94143 USA. [Goga, Andrei] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Huang, Bo] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA USA. [Huang, Bo] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA. [Raffai, Robert L.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. [Raffai, Robert L.] VA Med Ctr, San Francisco, CA USA. [Lai, Charles P.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Krichevsky, Anna M.] Brigham & Womens Hosp, Dept Neurol, Ann Romney Ctr Neurol Dis, Boston, MA 02115 USA. [Krichevsky, Anna M.] Harvard Univ, Sch Med, Boston, MA USA. [Mateescu, Bogdan; Voinnet, Olivier] Swiss Fed Inst Technol Zurich ETH Zurich, Zurich, Switzerland. [Greiner, Vanille J.; McManus, Michael T.] Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA. [Hunter, Craig] Harvard Univ, Cambridge, MA 02138 USA. RP Patton, JG (reprint author), Vanderbilt Univ, Dept Biol Sci, Box 1820 Stn B, Nashville, TN 37235 USA. EM James.G.Patton@Vanderbilt.edu RI Mateescu, bogdan/A-3101-2014 FU NCI NIH HHS [R01 CA163563, U19 CA179514, U19 CA179512]; NHLBI NIH HHS [P01 HL116263, R01 HL128996]; NIDDK NIH HHS [P30 DK026743, P30 DK058404, P30 DK063720] NR 73 TC 11 Z9 11 U1 1 U2 3 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2001-3078 J9 J EXTRACELL VESICLES JI J. Extracell. Vesicles PY 2015 VL 4 SI SI AR UNSP 27494 DI 10.3402/jev.v4.27494 PG 8 WC Cell Biology SC Cell Biology GA CW5ZW UT WOS:000365077100003 PM 26320939 ER PT J AU Quesenberry, PJ Aliotta, J Camussi, G Abdel-Mageed, AB Wen, S Goldberg, L Zhang, HG Tetta, C Franklin, J Coffey, RJ Danielson, K Subramanya, V Ghiran, I Das, S Chen, CC Pusic, KM Pusic, AD Chatterjee, D Kraig, RP Balaj, L Dooner, M AF Quesenberry, Peter J. Aliotta, Jason Camussi, Giovanni Abdel-Mageed, Asim B. Wen, Sicheng Goldberg, Laura Zhang, Huang-Ge Tetta, Ciro Franklin, Jeffrey Coffey, Robert J. Danielson, Kirsty Subramanya, Vinita Ghiran, Ionita Das, Saumya Chen, Clark C. Pusic, Kae M. Pusic, Aya D. Chatterjee, Devasis Kraig, Richard P. Balaj, Leonora Dooner, Mark TI Potential functional applications of extracellular vesicles: a report by the NIH Common Fund Extracellular RNA Communication Consortium SO JOURNAL OF EXTRACELLULAR VESICLES LA English DT Article DE extracellular vesicles; cell fate change; functional effects; renal; pulmonary heart disease; cancer ID MESENCHYMAL STEM-CELLS; EXOSOME-LIKE NANOPARTICLES; COLORECTAL-CANCER CELLS; STROMAL CELLS; INTERCELLULAR COMMUNICATION; DRUG-DELIVERY; BONE-MARROW; OLIGODENDROCYTE DIFFERENTIATION; MICROVESICLES PROTECT; THERAPEUTIC AGENTS AB The NIH Extracellular RNA Communication Program's initiative on clinical utility of extracellular RNAs and therapeutic agents and developing scalable technologies is reviewed here. Background information and details of the projects are presented. The work has focused on modulation of target cell fate by extracellular vesicles (EVs) and RNA. Work on plant-derived vesicles is of intense interest, and non-mammalian sources of vesicles may represent a very promising source for different therapeutic approaches. Retro-viral-like particles are intriguing. Clearly, EVs share pathways with the assembly machinery of several other viruses, including human endogenous retrovirals (HERVs), and this convergence may explain the observation of viral-like particles containing viral proteins and nucleic acid in EVs. Dramatic effect on regeneration of damaged bone marrow, renal, pulmonary and cardiovascular tissue is demonstrated and discussed. These studies show restoration of injured cell function and the importance of heterogeneity of different vesicle populations. The potential for neural regeneration is explored, and the capacity to promote and reverse neoplasia by EV exposure is described. The tremendous clinical potential of EVs underlies many of these projects, and the importance of regulatory issues and the necessity of general manufacturing production (GMP) studies for eventual clinical trials are emphasized. Clinical trials are already being pursued and should expand dramatically in the near future. C1 [Quesenberry, Peter J.; Aliotta, Jason; Wen, Sicheng; Goldberg, Laura; Chatterjee, Devasis; Dooner, Mark] Brown Univ, Warren Alpert Med Sch, Dept Med, Providence, RI 02912 USA. [Camussi, Giovanni; Tetta, Ciro] Univ Turin, Dept Med Sci, Turin, Italy. [Abdel-Mageed, Asim B.] Tulane Univ, Sch Med, Dept Urol, New Orleans, LA 70112 USA. [Abdel-Mageed, Asim B.] Tulane Univ, Sch Med, Tulane Canc Ctr, New Orleans, LA 70112 USA. [Zhang, Huang-Ge] Univ Louisville, Dept Microbiol & Immunol, Louisville, KY 40292 USA. [Franklin, Jeffrey; Coffey, Robert J.] Vanderbilt Univ, Dept Mol Biol, Nashville, TN 37235 USA. [Danielson, Kirsty; Subramanya, Vinita; Ghiran, Ionita; Das, Saumya] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. [Chen, Clark C.] Univ Calif San Diego, Dept Surg, Ctr Theoret & Appl Neurooncol, San Diego, CA 92103 USA. [Pusic, Kae M.; Pusic, Aya D.; Kraig, Richard P.] Univ Chicago, Dept Neurol, Chicago, IL 60637 USA. [Balaj, Leonora] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Balaj, Leonora] Harvard Univ, Sch Med, Charlestown, MA USA. RP Quesenberry, PJ (reprint author), Rhode Isl Hosp, 593 Eddy St,George 302, Providence, RI 02903 USA. EM pquesenberry@lifespan.org RI Camussi, Giovanni/J-7624-2016 OI Camussi, Giovanni/0000-0003-2795-232X FU NCATS NIH HHS [UH2 TR000875, UH2 TR000880, UH2 TR000928, UH3 TR000880, UH3 TR000901, UH3 TR000918]; NCI NIH HHS [P50 CA095103, R01 CA163563, U19 CA179514, U19 CA179563]; NHLBI NIH HHS [R01 HL122547, T32 HL116249]; NIDDK NIH HHS [P30 DK058404] NR 105 TC 6 Z9 6 U1 4 U2 6 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2001-3078 J9 J EXTRACELL VESICLES JI J. Extracell. Vesicles PY 2015 VL 4 SI SI AR UNSP 27575 DI 10.3402/jev.v4.27575 PG 11 WC Cell Biology SC Cell Biology GA CW5ZW UT WOS:000365077100006 PM 26320942 ER PT J AU Yanez-Mo, M Siljander, PRM Andreu, Z Zavec, AB Borras, FE Buzas, EI Buzas, K Casal, E Cappello, F Carvalho, J Colas, E Cordeiro-da Silva, A Fais, S Falcon-Perez, JM Ghobrial, IM Giebel, B Gimona, M Graner, M Gursel, I Gursel, M Heegaard, NHH Hendrix, A Kierulf, P Kokubun, K Kosanovic, M Kralj-Iglic, V Kramer-Albers, EM Laitinen, S Lasser, C Lener, T Ligeti, E Line, A Lipps, G Llorente, A Lotvall, J Mancek-Keber, M Marcilla, A Mittelbrunn, M Nazarenko, I Nolte-t' Hoen, ENM Nyman, TA O'Driscoll, L Olivan, M Oliveira, C Pallinger, E del Portillo, HA Reventos, J Rigau, M Rohde, E Sammar, M Sanchez-Madrid, F Santarem, N Schallmoser, K Ostenfeld, MS Stoorvogel, W Stukelj, R Van der Grein, SG Vasconcelos, MH Wauben, MHM De Wever, O AF Yanez-Mo, Maria Siljander, Pia R. -M. Andreu, Zoraida Zavec, Apolonija Bedina Borras, Francesc E. Buzas, Edit I. Buzas, Krisztina Casal, Enriqueta Cappello, Francesco Carvalho, Joana Colas, Eva Cordeiro-da Silva, Anabela Fais, Stefano Falcon-Perez, Juan M. Ghobrial, Irene M. Giebel, Bernd Gimona, Mario Graner, Michael Gursel, Ihsan Gursel, Mayda Heegaard, Niels H. H. Hendrix, An Kierulf, Peter Kokubun, Katsutoshi Kosanovic, Maja Kralj-Iglic, Veronika Kraemer-Albers, Eva-Maria Laitinen, Saara Lasser, Cecilia Lener, Thomas Ligeti, Erzsebet Line, Aija Lipps, Georg Llorente, Alicia Lotvall, Jan Mancek-Keber, Mateja Marcilla, Antonio Mittelbrunn, Maria Nazarenko, Irina Nolte-t' Hoen, Esther N. M. Nyman, Tuula A. O'Driscoll, Lorraine Olivan, Mireia Oliveira, Carla Pallinger, Eva del Portillo, Hernando A. Reventos, Jaume Rigau, Marina Rohde, Eva Sammar, Marei Sanchez-Madrid, Francisco Santarem, N. Schallmoser, Katharina Ostenfeld, Marie Stampe Stoorvogel, Willem Stukelj, Roman Van der Grein, Susanne G. Helena Vasconcelos, M. Wauben, Marca H. M. De Wever, Olivier TI Biological properties of extracellular vesicles and their physiological functions SO JOURNAL OF EXTRACELLULAR VESICLES LA English DT Review DE extracellular vesicle; microvesicle; microparticle; exosome; physiology; prokaryote; eukaryote ID OUTER-MEMBRANE VESICLES; CELL-DERIVED EXOSOMES; MESENCHYMAL STEM-CELLS; INTESTINAL EPITHELIAL-CELLS; MATURE DENDRITIC CELLS; SYNCYTIOTROPHOBLAST MICROVILLOUS MEMBRANES; IMMUNE-MODULATORY FEATURES; PLANT-MICROBE INTERACTIONS; FACTOR PATHWAY INHIBITOR; HUMAN ENDOTHELIAL-CELLS AB In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system. C1 [Yanez-Mo, Maria; Andreu, Zoraida] Hosp Sta Cristina, Inst Invest Sanitarias Princesa IIS IP, Unidad Invest, Madrid, Spain. [Yanez-Mo, Maria; Andreu, Zoraida] UAM, Dept Biol Mol, ES-28009 Madrid, Spain. [Siljander, Pia R. -M.] Univ Helsinki, Dept Biosci, Div Biochem & Biotechnol, Extracellular Vesicle Res, FI-00014 Helsinki, Finland. [Siljander, Pia R. -M.] Univ Helsinki, Fac Pharm, Div Pharmaceut Biosci, FI-00014 Helsinki, Finland. [Zavec, Apolonija Bedina] Natl Inst Chem, Lab Mol Biol & Nanobiotechnol, Ljubljana, Slovenia. [Borras, Francesc E.] Germans Trias & Pujol Res Inst, IVECAT Grp, Badalona, Spain. [Borras, Francesc E.] Germans Trias & Pujol Univ Hosp, Serv Nephrol, Badalona, Spain. [Buzas, Edit I.; Pallinger, Eva] Semmelweis Univ, Dept Genet Cell & Immunobiol, H-1085 Budapest, Hungary. [Buzas, Krisztina] Hungarian Acad Sci, Biol Res Ctr, H-6701 Szeged, Hungary. [Buzas, Krisztina] Univ Szeged, Fac Dent, Szeged, Hungary. [Casal, Enriqueta; Falcon-Perez, Juan M.] CIBERehd, CIC BioGUNE, Metabol Unit, Derio, Spain. [Cappello, Francesco] Univ Palermo, Human Anat Sect, Dept Expt Biomed & Clin Neurosci, Palermo, Italy. [Cappello, Francesco] Euromediterranean Inst Sci & Technol, Palermo, Italy. [Carvalho, Joana; Cordeiro-da Silva, Anabela; Oliveira, Carla; Santarem, N.; Helena Vasconcelos, M.] Univ Porto, Inst Invest & Inovacao Saude, P-4100 Oporto, Portugal. [Carvalho, Joana; Oliveira, Carla] Univ Porto IPATIMUP, Inst Mol Pathol & Immunol, Express Regulat Canc, Oporto, Portugal. [Colas, Eva; Olivan, Mireia; Reventos, Jaume; Rigau, Marina] Vall Hebron Inst Res, Res Unit Biomed & Translat Oncol, Barcelona, Spain. [Colas, Eva; Olivan, Mireia; Reventos, Jaume; Rigau, Marina] Autonomous Univ Barcelona, Barcelona, Spain. [Cordeiro-da Silva, Anabela; Santarem, N.] Univ Porto, IBMC, P-4100 Oporto, Portugal. [Cordeiro-da Silva, Anabela] Univ Porto, Fac Pharm, Dept Biol Sci, P-4100 Oporto, Portugal. [Fais, Stefano] Natl Inst Hlth ISS, Dept Therapeut Res & Med Evaluat, Antitumour Drugs Sect, Rome, Italy. [Falcon-Perez, Juan M.] Basque Fdn Sci, Ikerbasque, Bilbao, Spain. [Ghobrial, Irene M.; Kokubun, Katsutoshi] Dana Farber Canc Inst, Boston, MA 02115 USA. [Giebel, Bernd] Univ Duisburg Essen, Univ Hosp Essen, Inst Transfus Med, Essen, Germany. [Gimona, Mario; Lener, Thomas; Rohde, Eva; Schallmoser, Katharina] PMU, Spinal Cord Injury & Tissue Regenerat Ctr Salzbur, Salzburg, Austria. [Gimona, Mario; Lener, Thomas; Rohde, Eva; Schallmoser, Katharina] Salzburger Landeskliniken GesmbH SALK, Univ Klinikum, Dept Blood Grp Serol & Transfus Med, Salzburg, Austria. [Graner, Michael] Univ Colorado, Dept Neurosurg, Denver, CO 80202 USA. [Gursel, Ihsan] Bilkent Univ, Therapeut Oligonucleotide Res Lab, Dept Mol Biol & Genet, Thorlab, Ankara, Turkey. [Gursel, Mayda] Middle E Tech Univ, Dept Biol Sci, TR-06531 Ankara, Turkey. [Heegaard, Niels H. H.] Univ Southern Denmark, Odense Univ Hosp, Dept Clin Biochem & Pharmacol, Odense, Denmark. [Heegaard, Niels H. H.] Statens Serum Inst, Dept Clin Biochem Immunol & Genet, Analyt Prot Chem, DK-2300 Copenhagen, Denmark. [Hendrix, An; De Wever, Olivier] Ghent Univ Hosp, Dept Radiat Oncol & Expt Canc Res, Lab Expt Canc Res, Ghent, Belgium. [Kierulf, Peter] Oslo Univ Hosp, Dept Med Biochem, Bood Cell Res Grp, Oslo, Norway. [Kosanovic, Maja] Univ Belgrade, INEP, Inst Applicat Nucl Energy, Dept Immunochem & Glycobiol, Belgrade, Serbia. [Kralj-Iglic, Veronika; Stukelj, Roman] Univ Ljubljana, Fac Hlth Sci, Lab Clin Biophys, Ljubljana, Slovenia. [Kraemer-Albers, Eva-Maria] Johannes Gutenberg Univ Mainz, Mol Cell Biol & Focus Program Translat Neurosci, D-55122 Mainz, Germany. [Laitinen, Saara] Finnish Red Cross Blood Serv, Res & Cell Serv, Helsinki, Finland. [Lasser, Cecilia; Lotvall, Jan] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Krefting Res Ctr, Gothenburg, Sweden. [Ligeti, Erzsebet] Semmelweis Univ, Dept Physiol, H-1085 Budapest, Hungary. [Line, Aija] Latvian Biomed Res & Study Ctr, Riga, Latvia. [Lipps, Georg] Univ Appl Sci & Arts Northwestern Switzerland, Sch Life Sci, Inst Chem & Bioanalyt, Muttenz, Switzerland. [Llorente, Alicia] Norwegian Radium Hosp, Inst Canc Res, Oslo Univ Hosp, Dept Mol Cell Biol, Oslo, Norway. [Mancek-Keber, Mateja] Natl Inst Chem, Biotechnol Lab, Ljubljana, Slovenia. [Mancek-Keber, Mateja] EN FIST Ctr Excellence, Ljubljana, Slovenia. [Marcilla, Antonio] Univ Valencia, Fac Farm, Dept Biol Celular & Parasitol, E-46010 Valencia, Spain. [Mittelbrunn, Maria; Sanchez-Madrid, Francisco] Ctr Nacl Invest Cardiovasc, Dept Vasc Biol & Inflammat, Madrid, Spain. [Nazarenko, Irina] Univ Freiburg, Inst Environm Hlth Sci, D-79106 Freiburg, Germany. [Nazarenko, Irina] Univ Freiburg, Hosp Infect ControlMed Ctr, D-79106 Freiburg, Germany. [Nolte-t' Hoen, Esther N. M.; Stoorvogel, Willem; Van der Grein, Susanne G.; Wauben, Marca H. M.] Univ Utrecht, Fac Vet Med, Dept Biochem & Cell Biol, Utrecht, Netherlands. [Nyman, Tuula A.] Univ Helsinki, Inst Biotechnol, FI-00014 Helsinki, Finland. [O'Driscoll, Lorraine] Univ Dublin Trinity Coll, Sch Pharm & Pharmaceut Sci, Dublin 2, Ireland. [O'Driscoll, Lorraine] Univ Dublin Trinity Coll, Trinity Biomed Sci Inst, Dublin 2, Ireland. [Oliveira, Carla] Univ Porto, Fac Med, Dept Pathol & Oncol, P-4100 Oporto, Portugal. [del Portillo, Hernando A.] Univ Barcelona, Hosp Clin, Barcelona Ctr Int Hlth Res CRESIB, ISGlobal, Barcelona, Spain. [del Portillo, Hernando A.] Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain. [Reventos, Jaume] Univ Int Catalunya, Dept Ciencies Basiques, Barcelona, Spain. [Reventos, Jaume] Inst Recerca Biomed Bellvitge, Barcelona, Spain. [Sammar, Marei] ORT Braude Coll, Dept Biotechnol Engn, Karmiel, Israel. [Sanchez-Madrid, Francisco] Hosp Princesa, Inst Invest Sanitarias Princesa IIS IP, Serv Inmunol, Madrid, Spain. [Ostenfeld, Marie Stampe] Aarhus Univ Hosp, Dept Mol Med, DK-8000 Aarhus, Denmark. [Helena Vasconcelos, M.] Univ Porto IPATIMUP, Inst Mol Pathol & Immunol, Canc Drug Resistance Grp, Oporto, Portugal. [Helena Vasconcelos, M.] Univ Porto FFUP, Fac Pharm, Dept Biol Sci, Oporto, Portugal. RP Yanez-Mo, M (reprint author), UAM, Hosp Santa Cristina, Inst Invest Sanitaria Princesa, Membrane Microdomains Immun Lab,Unidad Invest,Dep, C Maestro Amadeo Vives 2, ES-28009 Madrid, Spain. EM maria.yanez@salud.madrid.org; pia.siljander@helsinki.fi RI Cappello, Francesco/F-9153-2012; Vasconcelos, M. Helena/J-9547-2013; Carvalho, Joana/J-9476-2013; Cordeiro-da-Silva, Anabela/J-7807-2013; marcilla, antonio/F-9996-2010; Oliveira, Carla/F-8188-2011; Falcon-Perez, Juan/F-5920-2011; Nazarenko, Irina/E-5714-2010; Mittelbrunn, Maria/I-5882-2015; Nyman, Tuula/A-8992-2016; Santarem, Nuno/J-8156-2013; Fais, Stefano/J-8638-2016; Sanchez-Madrid, Francisco/M-7889-2016; OI Yanez-Mo, Maria/0000-0001-7484-2866; Lotvall, Jan/0000-0001-9195-9249; Kosanovic, Maja/0000-0002-1143-1805; Cappello, Francesco/0000-0001-9288-1148; Siljander, Pia/0000-0003-2326-5821; Carvalho, Joana/0000-0001-9743-438X; Cordeiro-da-Silva, Anabela/0000-0003-2392-6087; marcilla, antonio/0000-0003-0004-0531; Oliveira, Carla/0000-0001-8340-2264; Santarem, Nuno/0000-0003-4973-9933; Mittelbrunn, Maria/0000-0003-3487-8762; Fais, Stefano/0000-0001-9060-2766; Sanchez-Madrid, Francisco/0000-0001-5303-0762; Colas, Eva/0000-0002-4439-4254 NR 716 TC 206 Z9 207 U1 46 U2 98 PU CO-ACTION PUBLISHING PI JARFALLA PA RIPVAGEN 7, JARFALLA, SE-175 64, SWEDEN SN 2001-3078 J9 J EXTRACELL VESICLES JI J. Extracell. Vesicles PY 2015 VL 4 AR 27066 DI 10.3402/jev.v4.27066 PG 60 WC Cell Biology SC Cell Biology GA CW5YH UT WOS:000365072700001 PM 25979354 ER PT J AU Vaivoda, R Vaine, C Boerstler, C Galloway, K Christmas, P AF Vaivoda, Rachel Vaine, Christine Boerstler, Cassandra Galloway, Kristy Christmas, Peter TI CYP4F18-Deficient Neutrophils Exhibit Increased Chemotaxis to Complement Component C5a SO JOURNAL OF IMMUNOLOGY RESEARCH LA English DT Article ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; LEUKOTRIENE B-4 METABOLISM; INFLAMMATORY BOWEL-DISEASE; OMEGA-HYDROXYLASE; CYTOCHROME P4504F; RENAL ISCHEMIA; EXPRESSION; LTB4; 5-LIPOXYGENASE; BIOSYNTHESIS AB CYP4Fs were first identified as enzymes that catalyze hydroxylation of leukotriene B-4 (LTB4). CYP4F18 has an unusual expression in neutrophils and was predicted to play a role in regulating LTB4-dependent inflammation. We compared chemotaxis of wildtype and Cyp4f18 knockout neutrophils using an in vitro assay. There was no significant difference in the chemotactic response to LTB4, but the response to complement component C5a increased 1.9-2.25-fold in knockout cells compared to wild-type (P < 0.01). This increase was still observed when neutrophils were treated with inhibitors of eicosanoid synthesis. There were no changes in expression of other CYP4 enzymes in knockout neutrophils that might compensate for loss of CYP4F18 or lead to differences in activity. A mouse model of dextran sodium sulfate colitis was used to investigate the consequences of increased C5a-dependent chemotaxis in vivo, but there was no significant difference in weight loss, disease activity, or colonic tissue myeloperoxidase between wild-type and Cyp4f18 knockout mice. This study demonstrates the limitations of inferring CYP4F function based on an ability to use LTB4 as a substrate, points to expanding roles for CYP4F enzymes in immune regulation, and underscores the in vivo challenges of CYP knockout studies. C1 [Vaivoda, Rachel; Vaine, Christine; Christmas, Peter] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Charlestown, MA 02129 USA. [Boerstler, Cassandra; Galloway, Kristy; Christmas, Peter] Radford Univ, Dept Biol, Radford, VA 24142 USA. RP Christmas, P (reprint author), Massachusetts Gen Hosp, Dept Med, Div Nephrol, Charlestown, MA 02129 USA. EM pchristma2@radford.edu OI Vaine, Christine/0000-0003-2645-8223 FU National Institutes of Health [R01DK074821]; College of Science and Technology, Radford University FX This project was supported by National Institutes of Health Grant R01DK074821 (to Peter Christmas) and a grant from the College of Science and Technology, Radford University. NR 33 TC 1 Z9 1 U1 1 U2 1 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 2314-8861 EI 2314-7156 J9 J IMMUNOL RES JI J Immunol. Res. PY 2015 AR 250456 DI 10.1155/2015/250456 PG 10 WC Immunology SC Immunology GA CW3EM UT WOS:000364874800001 ER PT J AU Gulur, P Koury, K Arnstein, P Lee, H McCarthy, P Coley, C Mort, E AF Gulur, Padma Koury, Katharine Arnstein, Paul Lee, Hang McCarthy, Patricia Coley, Christopher Mort, Elizabeth TI Morphine versus Hydromorphone: Does Choice of Opioid Influence Outcomes? SO PAIN RESEARCH AND TREATMENT LA English DT Article ID PAIN MANAGEMENT; ADVERSE EVENTS; PHARMACOKINETICS; EFFICACY; SAFETY AB Morphine has traditionally been considered the first line agent for analgesia in hospitals; however, in the last few years there has been a shift towards the use of hydromorphone as a first line agent. We conducted a hospital population based observational study to evaluate the increasing use of hydromorphone over morphine in both medical and surgical populations. Additionally, we assessed the effect of this trend on three key outcomes, including adverse events, length of stay, and readmission rates. We evaluated data from the University Health Systems Consortium. Data from 38 hospitals from October 2010 to September 2013 was analyzed for patients treated with either hydromorphone or morphine. The use of morphine steadily decreased while use of hydromorphone increased in both medical and surgical groups. Rescue drugs were used more frequently in patients treated with hydromorphone in comparison to patients treated with morphine (p < 0.01). Patients receiving morphine tended to stay in the hospital for almost one day longer than patients receiving hydromorphone. However, 30-day all cause readmission rates were significantly higher in patients treated with hydromorphone (p < 0.01). Our study highlights that the choice of hydromorphone versus morphine may influence outcomes. There are implications related to resource utilization and these outcomes. C1 [Gulur, Padma; Koury, Katharine; Arnstein, Paul; Lee, Hang; McCarthy, Patricia; Coley, Christopher; Mort, Elizabeth] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gulur, P (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM pgulur@yahoo.com NR 28 TC 1 Z9 1 U1 0 U2 2 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 2090-1542 EI 2090-1550 J9 PAIN RES TREAT JI Pain Res. Treat. PY 2015 AR 482081 DI 10.1155/2015/482081 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA CW2UK UT WOS:000364848400001 ER PT J AU Tejon, G Manriquez, V De Calisto, J Flores-Santibanez, F Hidalgo, Y Crisostomo, N Fernandez, D Sauma, D Mora, JR Bono, MR Rosemblatt, M AF Tejon, Gabriela Manriquez, Valeria De Calisto, Jaime Flores-Santibanez, Felipe Hidalgo, Yessia Crisostomo, Natalia Fernandez, Dominique Sauma, Daniela Rodrigo Mora, J. Bono, Maria R. Rosemblatt, Mario TI Vitamin A Impairs the Reprogramming of Tregs into IL-17-Producing Cells during Intestinal Inflammation SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID REGULATORY T-CELLS; RETINOIC-ACID; BOWEL-DISEASE; TGF-BETA; DENDRITIC CELLS; CUTTING EDGE; TH17 CELLS; KAPPA-B; COLITIS; IL-2 AB Maintaining the identity of Foxp3(+) regulatory T cells (Tregs) is critical for controlling immune responses in the gut, where an imbalance between Tregs and T effector cells has been linked to inflammatory bowel disease. Accumulating evidence suggests that Tregs can convert intoTh17 cells and acquire an inflammatory phenotype. In this study, we used an adoptive transfer model of Ag-specific T cells to study the contribution of different factors to the reprogramming of in vitro-generated Treg cells (iTreg) into IL-17-producing cells in a mouse model of gut inflammation in vivo. Our results show that intestinal inflammation induces the reprogramming of iTreg cells into IL-17-producing cells and that vitamin Arestrains reprogramming in the gut. We also demonstrate that the presence of IL-2 during the in vitro generation of iTreg cells confers resistance to Th17 conversion but that IL-2 and retinoic acid (RA) cooperate to maintain Foxp3 expression following stimulation under Th17-polarizing conditions. Additionally, although IL-2 and RA differentially regulate the expression of different Treg cell suppressive markers, Treg cells generated under different polarizing conditions present similar suppressive capacity. C1 [Tejon, Gabriela; Manriquez, Valeria; De Calisto, Jaime; Flores-Santibanez, Felipe; Hidalgo, Yessia; Crisostomo, Natalia; Fernandez, Dominique; Sauma, Daniela; Bono, Maria R.; Rosemblatt, Mario] Univ Chile, Fac Ciencias, Dept Biol, Santiago 7800024, Chile. [De Calisto, Jaime; Bono, Maria R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Gastrointestinal Unit, Boston, MA 02114 USA. [Rosemblatt, Mario] Fdn Ciencia & Vida, Santiago 7780272, Chile. [Rosemblatt, Mario] Univ Andres Bello, Fac Ciencias Biol, Santiago 8370146, Chile. RP Rosemblatt, M (reprint author), Univ Chile, Fac Ciencias, Dept Biol, Santiago 7800024, Chile. EM mrosemblatt@cienciavida.cl OI Tejon, Gabriela Paola/0000-0003-4865-2545; Manriquez Rojas, Valeria/0000-0001-5487-2216 FU FONDECYT [1100557, 1100448]; CONICYT [PFB16, 24110107]; MECESUP [UCH-0713] FX This work was supported by Grants 1100557 and 1100448 from FONDECYT and by PFB16 from CONICYT. Gabriela Tejon received additional support from MECESUP Grant UCH-0713 and Grant 24110107 from CONICYT. NR 40 TC 5 Z9 5 U1 2 U2 9 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2015 AR 137893 DI 10.1155/2015/137893 PG 8 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA CW0EU UT WOS:000364663000001 ER PT J AU Partridge, AH AF Partridge, Ann H. TI Chemotherapy in Premenopausal Breast Cancer Patients SO BREAST CARE LA English DT Review DE Breast Cancer; Adjuvant chemotherapy; Premenopausal women; Long-term effects ID PLUS ZOLEDRONIC ACID; ADJUVANT CHEMOTHERAPY; ENDOCRINE THERAPY; RANDOMIZED-TRIAL; YOUNG-WOMEN; OVARIAN SUPPRESSION; FERTILITY CONCERNS; 1ST REPORT; STAGE; AGE AB Evidence has long demonstrated that premenopausal women obtain the greatest benefit from adjuvant chemotherapy overall, with risk reduction increasing with decreasing age. The chemoendocrine effect of chemotherapy has only more recently been documented as impacting on outcomes for women with hormone receptor-positive breast cancer, and recent data have elucidated the optimal strategies for manipulating the menopausal status to improve disease outcomes, without necessarily including cytotoxic chemotherapy. Still, many premenopausal women will require adjuvant cytotoxic chemotherapy, and the effects of treatment on women diagnosed with breast cancer in the premenopausal setting can have important implications both on their breast cancer outcomes and on comorbidities and psychosocial outcomes. This article describes the most recent information and issues surrounding the indications, effects, and special considerations for adjuvant chemotherapy in premenopausal women with breast cancer, in an effort to inform their care. (C) 2015 C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Partridge, AH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM ahpartridge@partners.org NR 45 TC 3 Z9 3 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-3791 EI 1661-3805 J9 BREAST CARE JI Breast Care PY 2015 VL 10 IS 5 BP 307 EP 310 DI 10.1159/000441371 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA CV9JV UT WOS:000364604400002 PM 26688676 ER PT S AU Senderovich, A Rogge-Solti, A Gal, A Mendling, J Mandelbaum, A Kadish, S Bunnell, CA AF Senderovich, Arik Rogge-Solti, Andreas Gal, Avigdor Mendling, Jan Mandelbaum, Avishai Kadish, Sarah Bunnell, Craig A. BE MotahariNezhad, HR Recker, J Weidlich, M TI Data-Driven Performance Analysis of Scheduled Processes SO BUSINESS PROCESS MANAGEMENT, BPM 2015 SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 13th International Conference on Business Process Management (BPM) CY AUG 31-SEP 03, 2015 CL Univ Innsbruck, Innsbruck, AUSTRIA SP Bizagi, Prologics, Minitlabs, IBM Res, Signavio, Exformatics, SAP HO Univ Innsbruck ID PETRI NETS; SYSTEMS AB The performance of scheduled business processes is of central importance for services and manufacturing systems. However, current techniques for performance analysis do not take both queueing semantics and the process perspective into account. In this work, we address this gap by developing a novel method for utilizing rich process logs to analyze performance of scheduled processes. The proposed method combines simulation, queueing analytics, and statistical methods. At the heart of our approach is the discovery of an individual-case model from data, based on an extension of the Colored Petri Nets formalism. The resulting model can be simulated to answer performance queries, yet it is computational inefficient. To reduce the computational cost, the discovered model is projected into Queueing Networks, a formalism that enables efficient performance analytics. The projection is facilitated by a sequence of folding operations that alter the structure and dynamics of the Petri Net model. We evaluate the approach with a real-world dataset from Dana-Farber Cancer Institute, a large outpatient cancer hospital in the United States. C1 [Senderovich, Arik; Gal, Avigdor; Mandelbaum, Avishai] Technion Israel Inst Technol, Haifa, Israel. [Rogge-Solti, Andreas; Mendling, Jan] Vienna Univ Econ & Business, Vienna, Austria. [Kadish, Sarah; Bunnell, Craig A.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Senderovich, A (reprint author), Technion Israel Inst Technol, Haifa, Israel. EM sariks@tx.technion.ac.il; andreas.rogge-solti@wu.ac.at; avigal@ie.technion.ac.il; jan.mendling@wu.ac.at; avim@ie.technion.ac.il; sarah_kadish@dfci.harvard.edu; craig_bunnell@dfci.harvard.edu OI Solti, Andreas/0000-0002-0537-6598 NR 23 TC 2 Z9 2 U1 1 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-319-23063-4; 978-3-319-23062-7 J9 LECT NOTES COMPUT SC PY 2015 VL 9253 BP 35 EP 52 DI 10.1007/978-3-319-23063-4_3 PG 18 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods SC Computer Science GA BD9IB UT WOS:000364712100003 ER PT J AU Labouliere, CD Tarquini, SJ Totura, CMW Kutash, K Karver, MS AF Labouliere, Christa D. Tarquini, Sarah J. Totura, Christine M. W. Kutash, Krista Karver, Marc S. TI Revisiting the Concept of Knowledge How Much Is Learned by Students Participating in Suicide Prevention Gatekeeper Training? SO Crisis-The Journal of Crisis Intervention and Suicide Prevention LA English DT Article DE suicide prevention; adolescents; gatekeeper training; school; open-ended assessment ID AWARENESS CURRICULUM; SCHOOL; ADOLESCENTS; PROGRAMS; IMPACT; RISK AB Background: Although gatekeeper training is effective at increasing knowledge, some question the effectiveness of these programs due to high pretraining knowledge levels. However, knowledge scores may be artificially inflated when students guess answer options correctly but lack information needed to assist suicidal peers. Aims: To use free-recall questions to evaluate suicide prevention knowledge and compare levels of knowledge using this methodology with established assessment methods in the literature. Method: Free-recall knowledge questions were examined before and after participation in a student gatekeeper training program. Focus groups with students enriched interpretation of quantitative results. Results: Unlike in studies using forced-choice assessment, students' baseline knowledge was markedly low using free-recall questions and, despite making significant improvement from pretraining levels, posttraining knowledge barely approached passable levels. Focus group findings suggest that training sessions may need to be more engaging and interactive in order to improve knowledge transfer. Conclusion: Free-recall questions may provide a less inflated measure of accessible knowledge learned from school-based suicide prevention curricula. Evaluators and programmatic partners should be cognizant of this methodological issue and consider using a mix of assessment methodologies to determine students' actual levels of knowledge after participation in gatekeeper training. C1 [Labouliere, Christa D.] Columbia Univ, Med Ctr, New York State Psychiat Inst, Div Child & Adolescent Psychiat, New York, NY 10032 USA. [Tarquini, Sarah J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Totura, Christine M. W.] Auburn Univ, Auburn, AL 36849 USA. [Kutash, Krista] Univ S Florida, Louis De La Parte Florida Mental Hlth Inst, Tampa, FL USA. [Karver, Marc S.] Univ S Florida, Dept Psychol, Tampa, FL 33620 USA. RP Labouliere, CD (reprint author), Columbia Univ, Med Ctr, New York State Psychiat Inst, 1051 Riverside Dr Unit 78, New York, NY 10032 USA. EM labouli@nyspi.columbia.edu FU Substance Abuse and Mental Health Administration grants [SM57442-01, 02-3] FX Special thanks to Sarah Gunderson, Laurie Dempsey, and Renee Brown Hangartner for their invaluable assistance. This research was supported by Substance Abuse and Mental Health Administration grants (#SM57442-01, 02-3) to Drs. Karver, Kutash, and Totura. NR 36 TC 1 Z9 1 U1 0 U2 6 PU HOGREFE & HUBER PUBLISHERS PI GOTTINGEN PA ROHNSWEG 25, D-37085 GOTTINGEN, GERMANY SN 0227-5910 EI 2151-2396 J9 CRISIS JI Crisis PY 2015 VL 36 IS 4 BP 274 EP 280 DI 10.1027/0227-5910/a000323 PG 7 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA CV7FX UT WOS:000364438900007 PM 26440624 ER PT B AU Mohlman, J Deckersbach, T Weissman, AS AF Mohlman, Jan Deckersbach, Thilo Weissman, Adam S. BE Mohlman, J Deckersbach, T Weissman, AS TI INTRODUCTION Integrating Brain and Body Measures with the Study of Psychological Disorders SO FROM SYMPTOM TO SYNAPSE: A NEUROCOGNITIVE PERSPECTIVE ON CLINICAL PSYCHOLOGY LA English DT Editorial Material; Book Chapter ID PEDIATRIC ANXIETY DISORDERS; COGNITIVE-BEHAVIOR THERAPY; BIPOLAR DISORDER; PSYCHOSOCIAL DISABILITY; ACADEMIC-ACHIEVEMENT; SUSTAINED ATTENTION; EXECUTIVE FUNCTION; FOLLOW-UP; DEPRESSION; WORK C1 [Mohlman, Jan] William Paterson Univ, Dept Psychol, Wayne, NJ 07470 USA. [Deckersbach, Thilo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. [Weissman, Adam S.] Columbia Univ, Child & Family Cognit Behav Psychol, New York, NY 10027 USA. RP Mohlman, J (reprint author), William Paterson Univ, Dept Psychol, Wayne, NJ 07470 USA. NR 69 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI ABINGDON PA 2 PARK SQ, MILTON PARK, ABINGDON OX14 4RN, OXFORD, ENGLAND BN 978-0-415-83587-9; 978-0-203-50713-1; 978-0-415-83586-2 PY 2015 BP 1 EP 17 PG 17 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA BD8YC UT WOS:000364454700001 ER PT B AU Moshier, SJ Calkins, AW Kredlow, MA Otto, MW AF Moshier, Samantha J. Calkins, Amanda W. Kredlow, Maria Alexandra Otto, Michael W. BE Mohlman, J Deckersbach, T Weissman, AS TI NEUROCOGNITIVE PERSPECTIVES ON ANXIETY AND RELATED DISORDERS SO From Symptom to Synapse: A Neurocognitive Perspective on Clinical Psychology LA English DT Article; Book Chapter ID POSTTRAUMATIC-STRESS-DISORDER; OBSESSIVE-COMPULSIVE DISORDER; COGNITIVE-BEHAVIORAL THERAPY; GENERALIZED SOCIAL PHOBIA; PLACEBO-CONTROLLED TRIAL; CEREBRAL-BLOOD-FLOW; RANDOMIZED CONTROLLED-TRIAL; D-CYCLOSERINE ENHANCEMENT; MEDIAL PREFRONTAL CORTEX; FEAR-POTENTIATED STARTLE C1 [Moshier, Samantha J.; Otto, Michael W.] Boston Univ, Dept Psychol & Brain Sci, Boston, MA 02215 USA. [Calkins, Amanda W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. [Kredlow, Maria Alexandra] Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP Moshier, SJ (reprint author), Boston Univ, Dept Psychol & Brain Sci, Boston, MA 02215 USA. NR 258 TC 0 Z9 0 U1 3 U2 4 PU ROUTLEDGE PI ABINGDON PA 2 PARK SQ, MILTON PARK, ABINGDON OX14 4RN, OXFORD, ENGLAND BN 978-0-415-83587-9; 978-0-203-50713-1; 978-0-415-83586-2 PY 2015 BP 75 EP 120 PG 46 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA BD8YC UT WOS:000364454700004 ER PT B AU Deckersbach, T Kaur, N Hansen, NS AF Deckersbach, Thilo Kaur, Navneet Hansen, Natasha S. BE Mohlman, J Deckersbach, T Weissman, AS TI BIPOLAR DISORDER A Neurocognitive Perspective SO From Symptom to Synapse: A Neurocognitive Perspective on Clinical Psychology LA English DT Article; Book Chapter ID TREATMENT ENHANCEMENT PROGRAM; SOCIAL RHYTHM THERAPY; OBSESSIVE-COMPULSIVE DISORDER; RANDOMIZED CONTROLLED-TRIAL; MAJOR DEPRESSIVE-DISORDERS; WEEKLY SYMPTOMATIC STATUS; WORKING-MEMORY TASK; I DISORDER; COGNITIVE REMEDIATION; MOOD DISORDERS C1 [Deckersbach, Thilo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. [Kaur, Navneet] Tufts Univ, Harvard Univ, Sch Med, Massachusetts Gen Hosp, Medford, MA 02155 USA. [Hansen, Natasha S.] Univ Boulder, Boulder, CO USA. RP Deckersbach, T (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. NR 124 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI ABINGDON PA 2 PARK SQ, MILTON PARK, ABINGDON OX14 4RN, OXFORD, ENGLAND BN 978-0-415-83587-9; 978-0-203-50713-1; 978-0-415-83586-2 PY 2015 BP 278 EP 302 PG 25 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA BD8YC UT WOS:000364454700010 ER PT B AU McQuaid, JR AF McQuaid, John R. BE Mohlman, J Deckersbach, T Weissman, AS TI TREATMENT OF PHANTOM LIMB PAIN Application of Neuroscience to a Disorder of Neuroplasticity SO From Symptom to Synapse: A Neurocognitive Perspective on Clinical Psychology LA English DT Article; Book Chapter ID MIRROR THERAPY; MOTOR CORTEX; CASE SERIES; AMPUTEES; AMPUTATION; REORGANIZATION; MOVEMENTS; REPRESENTATIONS; PLASTICITY C1 UCSF, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. RP McQuaid, JR (reprint author), UCSF, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. NR 55 TC 0 Z9 0 U1 2 U2 9 PU ROUTLEDGE PI ABINGDON PA 2 PARK SQ, MILTON PARK, ABINGDON OX14 4RN, OXFORD, ENGLAND BN 978-0-415-83587-9; 978-0-203-50713-1; 978-0-415-83586-2 PY 2015 BP 303 EP 322 PG 20 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA BD8YC UT WOS:000364454700011 ER PT J AU Suzan, E Aviram, J Treister, R Eisenberg, E Pud, D AF Suzan, Erica Aviram, Joshua Treister, Roi Eisenberg, Elon Pud, Dorit TI Individually based measurement of temporal summation evoked by a noxious tonic heat paradigm SO JOURNAL OF PAIN RESEARCH LA English DT Article DE heat pain; healthy volunteers; individual differences; pain perception; temporal summation ID 2ND PAIN; GENDER; STIMULATION; ANALGESIA; SEX AB Background: A model for measuring temporal summation (TS) by tonic noxious stimulation was recently proposed. However, methodological variations between studies make it difficult to reach a consensus regarding the way TS should be applied and calculated. The present study aimed to present a calculation method of TS magnitude produced by a tonic heat model in a large cohort of healthy subjects. Methods: Noxious heat stimulation (46.5 degrees C/2 minutes) was applied to the forearm of 154 subjects who continuously rated pain intensity using a computerized visual analog scale. TS was calculated by "mean group" and "individual" approaches. Results: A "typical" pattern of pain response, characterized by a peak pain followed by a decrease in intensity to a nadir and subsequently a progressive increase in pain scores, was exhibited by 86.4% of the subjects. Using the "mean group" and "individual" calculation approaches, the mean +/- standard deviation magnitudes of TS were 31.4 +/- 27.5 and 41.0 +/- 26.0, respectively (P<0.001). Additionally, using the individualized approach, we identified a different ("atypical") response pattern among the rest of the subjects (13.6%). Conclusion: The results support the tonic heat model of TS for future utilization. The individualized TS calculation method seems advantageous since it better reflects individual magnitudes of TS. C1 [Suzan, Erica; Eisenberg, Elon] Technion Israel Inst Technol, Rappaport Fac Med, Haifa, Israel. [Suzan, Erica; Eisenberg, Elon] Rambam Hlth Care Campus, Inst Pain Med, IL-31096 Haifa, Israel. [Aviram, Joshua; Pud, Dorit] Univ Haifa, Fac Social Welf & Hlth Sci, IL-31999 Haifa, Israel. [Treister, Roi] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Treister, Roi] Harvard Univ, Sch Med, Boston, MA USA. RP Suzan, E (reprint author), Rambam Hlth Care Campus, Inst Pain Med, POB 9602, IL-31096 Haifa, Israel. EM erica.dol@gmail.com NR 22 TC 2 Z9 2 U1 1 U2 1 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-7090 J9 J PAIN RES JI J. Pain Res. PY 2015 VL 8 BP 409 EP 415 DI 10.2147/JPR.S83352 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA CW0ZN UT WOS:000364719100002 PM 26213476 ER PT J AU Daveler, B Salatin, B Grindle, GG Candiotti, J Wang, HW Cooper, RA AF Daveler, Brandon Salatin, Benjamin Grindle, Garrett G. Candiotti, Jorge Wang, Hongwu Cooper, Rory A. TI Participatory design and validation of mobility enhancement robotic wheelchair SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE barriers; design; electric powered wheelchair; mobility; mobility enhancement; movement; robotics; traction control; transportation; wheelchair ID PERSONAL MOBILITY; MANIPULATION; ISSUES; INJURIES; BARRIERS; ADULTS; TRENDS; USERS AB The design of the mobility enhancement robotic wheelchair (MEBot) was based on input from electric powered wheelchair (EPW) users regarding the conditions they encounter when driving in both indoor and outdoor environments that may affect their safety and result in them becoming immobilized, tipping over, or falling out of their wheelchair. Phase I involved conducting a participatory design study to understand the conditions and barriers EPW users found to be difficult to drive in/over. Phase II consisted of creating a computer-aided design (CAD) prototype EPW to provide indoor and outdoor mobility that addressed these conditions with advanced applications. Phase III involved demonstrating the advanced applications and gathering feedback from end users about the likelihood they would use the advanced applications. The CAD prototype incorporated advanced applications, including self-leveling, curb climbing, and traction control, that addressed the challenging conditions and barriers discussed with EPW users (n = 31) during the participatory design study. Feedback on the CAD design and applications in phase III from end users (n = 12) showed a majority would use self-leveling (83%), traction control (83%), and curb climbing (75%). The overall design of MEBot received positive feedback from EPW users. However, these opinions will need to be reevaluated through user trials as the design advances. C1 [Daveler, Brandon; Grindle, Garrett G.; Candiotti, Jorge; Wang, Hongwu; Cooper, Rory A.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Daveler, Brandon; Grindle, Garrett G.; Candiotti, Jorge; Wang, Hongwu; Cooper, Rory A.] Dept Vet Affairs VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA USA. [Salatin, Benjamin] Hunter Holmes McGuire VA Med Ctr, Dept Phys Med & Rehabil Assist Technol, Richmond, VA USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, 6425 Penn Ave,Suite 400, Pittsburgh, PA 15206 USA. EM rcooper@pitt.edu FU Department of Veterans Affairs Rehabilitation Research and Development Center of Excellence [B9250-C]; National Science Foundation Interdisciplinary Research Training in Rehabilitation Engineering [DGE1144584]; National Science Foundation Quality of Life Engineering Research Center [EEC0540865] FX This material was based on work supported by the Department of Veterans Affairs Rehabilitation Research and Development Center of Excellence (grant B9250-C), and the National Science Foundation Interdisciplinary Research Training in Rehabilitation Engineering (grant DGE1144584), and the National Science Foundation Quality of Life Engineering Research Center (grant EEC0540865). NR 28 TC 1 Z9 1 U1 3 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 2015 VL 52 IS 6 BP 739 EP 750 DI 10.1682/JRRD.2014.11.0278 PG 12 WC Rehabilitation SC Rehabilitation GA CV8BM UT WOS:000364501500010 PM 26562492 ER PT B AU Korsten, MA Ancha, HR Kaminski, M AF Korsten, Mark A. Ancha, Hanumantha R. Kaminski, Miriam BE Sands, BE TI Approach to Constipation SO Mount Sinai Expert Guides: Gastroenterology LA English DT Article; Book Chapter ID NORTH-AMERICA; TRIAL C1 [Korsten, Mark A.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Korsten, Mark A.] James J Peters VA Med Ctr, Gastroenterol, Bronx, NY USA. [Ancha, Hanumantha R.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Kaminski, Miriam] Tech Univ Munich, Klinikum Rechts Isar, Dept Neurol, D-80290 Munich, Germany. RP Korsten, MA (reprint author), Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. NR 10 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 978-1-118-93275-9; 978-1-118-51996-7 PY 2015 BP 45 EP 55 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BD6ZK UT WOS:000362779400007 ER PT B AU Sauk, J AF Sauk, Jenny BE Sands, BE TI Infectious Enteritis and Colitis; Bacterial Food Poisoning; Intestinal Protozoa and Helminthic Infestations SO Mount Sinai Expert Guides: Gastroenterology LA English DT Article; Book Chapter ID TRAVELERS DIARRHEA; EPIDEMIOLOGY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med, Boston, MA 02115 USA. RP Sauk, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med, Boston, MA 02115 USA. NR 9 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 978-1-118-93275-9; 978-1-118-51996-7 PY 2015 BP 250 EP 259 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BD6ZK UT WOS:000362779400027 ER PT B AU Fong, ZV Lillemoe, KD AF Fong, Zhi Ven Lillemoe, Keith D. BE Beger, HG Nakao, A Neoptolemos, JP Peng, SY Sarr, MG TI Standards of oncologic pancreatic surgery SO PANCREATIC CANCER, CYSTIC NEOPLASMS, AND ENDOCRINE TUMORS: DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID PYLORUS-PRESERVING PANCREATICODUODENECTOMY; PROSPECTIVE-RANDOMIZED-TRIAL; INTERNATIONAL STUDY-GROUP; LONG-TERM SURVIVAL; MINIMAL POSTOPERATIVE COMPLICATIONS; LAPAROSCOPIC RESECTION APPROPRIATE; PREOPERATIVE BILIARY DRAINAGE; SINGLE-INSTITUTION EXPERIENCE; PLACEBO-CONTROLLED TRIAL; RIGHT HEPATIC-ARTERY C1 [Fong, Zhi Ven; Lillemoe, Keith D.] Massachusetts Gen Hosp, Dept Surg, Surg, Boston, MA 02114 USA. RP Fong, ZV (reprint author), Massachusetts Gen Hosp, Dept Surg, Surg, Boston, MA 02114 USA. NR 89 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 978-1-118-30781-6; 978-0-470-67318-8 PY 2015 BP 29 EP 46 D2 10.1002/9781118307816 PG 18 WC Oncology; Gastroenterology & Hepatology SC Oncology; Gastroenterology & Hepatology GA BD7BR UT WOS:000362849500006 ER PT B AU Yoon, WJ Brugge, WR AF Yoon, Won Jae Brugge, William R. BE Beger, HG Nakao, A Neoptolemos, JP Peng, SY Sarr, MG TI Endoscopic ultrasonography and cystic fluid analysis of the pancreas: evidence of diagnostic measures SO Pancreatic Cancer, Cystic Neoplasms, and Endocrine Tumors: Diagnosis and Management LA English DT Article; Book Chapter ID FINE-NEEDLE-ASPIRATION; EUS; MANAGEMENT; NEOPLASMS; LESIONS; TUMORS C1 [Yoon, Won Jae] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Yoon, Won Jae] Inje Univ, Coll Med, Seoul Paik Hosp, Dept Internal Med, Seoul, South Korea. [Brugge, William R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med,Gastrointestinal Unit, Boston, MA USA. RP Yoon, WJ (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 19 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 978-1-118-30781-6; 978-0-470-67318-8 PY 2015 BP 221 EP 224 D2 10.1002/9781118307816 PG 4 WC Oncology; Gastroenterology & Hepatology SC Oncology; Gastroenterology & Hepatology GA BD7BR UT WOS:000362849500030 ER PT B AU Sahora, K Fernandez-del Castillo, C AF Sahora, Klaus Fernandez-del Castillo, Carlos BE Beger, HG Nakao, A Neoptolemos, JP Peng, SY Sarr, MG TI What are the pathologic criteria that justified observational management in patients with cystic neoplastic lesions of the pancreas? SO Pancreatic Cancer, Cystic Neoplasms, and Endocrine Tumors: Diagnosis and Management LA English DT Article; Book Chapter ID PAPILLARY MUCINOUS NEOPLASMS; INTERNATIONAL-CONSENSUS-GUIDELINES; RESECTION; SIZE; CONCOMITANT; MALIGNANCY; PREDICTORS; CARCINOMA; OBSERVE; OPERATE C1 [Sahora, Klaus; Fernandez-del Castillo, Carlos] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg,Dept Surg, Boston, MA 02138 USA. RP Sahora, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg,Dept Surg, Boston, MA 02138 USA. NR 24 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 978-1-118-30781-6; 978-0-470-67318-8 PY 2015 BP 229 EP 232 D2 10.1002/9781118307816 PG 4 WC Oncology; Gastroenterology & Hepatology SC Oncology; Gastroenterology & Hepatology GA BD7BR UT WOS:000362849500032 ER PT B AU Sahora, K Fernandez-del Castillo, C AF Sahora, Klaus Fernandez-del Castillo, Carlos BE Beger, HG Nakao, A Neoptolemos, JP Peng, SY Sarr, MG TI Surgical management of mucinous cystic neoplastic lesions of the pancreas SO Pancreatic Cancer, Cystic Neoplasms, and Endocrine Tumors: Diagnosis and Management LA English DT Article; Book Chapter ID LAPAROSCOPIC DISTAL PANCREATECTOMY; EXPERIENCE; RESECTION; TRENDS; ENUCLEATION; PREGNANCY; LESSONS; BENIGN C1 [Sahora, Klaus; Fernandez-del Castillo, Carlos] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg,Dept Surg, Boston, MA 02138 USA. RP Sahora, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg,Dept Surg, Boston, MA 02138 USA. NR 30 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 978-1-118-30781-6; 978-0-470-67318-8 PY 2015 BP 243 EP 248 D2 10.1002/9781118307816 PG 6 WC Oncology; Gastroenterology & Hepatology SC Oncology; Gastroenterology & Hepatology GA BD7BR UT WOS:000362849500035 ER PT J AU Delgado, C Shieh, S Grimes, B Chertow, GM Dalrymple, LS Kaysen, GA Kornak, J Johansen, KL AF Delgado, Cynthia Shieh, Stephanie Grimes, Barbara Chertow, Glenn M. Dalrymple, Lorien S. Kaysen, George A. Kornak, John Johansen, Kirsten L. TI Association of Self-Reported Frailty with Falls and Fractures among Patients New to Dialysis SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Fracture; Frailty; Hemodialysis ID STAGE RENAL-DISEASE; HEMODIALYSIS-PATIENTS; HIP FRACTURE; ELDERLY PERSONS; INCREASED RISK; MORTALITY; OLDER; MORBIDITY; INJURIES; COMMUNITY AB Background: Although frailty has been linked to higher risk of falls and fracture in the general population, only few studies have examined the extent to which frailty is associated with these outcomes among patients with end-stage renal disease, who are at particularly high risk for these events. Methods: A total of 1,646 patients who were beginning maintenance hemodialysis in 297 dialysis units throughout the United States from September 2005 to June 2007 were enrolled in the Comprehensive Dialysis Study, and 1,053 Medicare beneficiaries were included in this study. Self-reported frailty was defined by the patients endorsing 2 or more of the following: poor physical functioning, exhaustion or low physical activity. Falls and fractures requiring medical attention were identified through Medicare claims data. We examined the association between frailty and the time to first fall or fracture using the Fine-Gray modification of Cox proportional hazards regression, adjusted for demographics, Quetelet's body mass index, diabetes mellitus, heart failure and atherosclerosis. Results: Seventy-seven percent of patients were frail by self-report. The median length of follow-up was 2.5 (1.0-3.9) years. Crude rates of first medically urgent falls or fractures were 66 and 126 per 1,000 personyears in non-frail and self-reported frail participants, respectively. After accounting for demographic factors, comorbidities and the competing risk of death, self-reported frailty was associated with a higher risk of falls or fractures requiring medical attention (hazards ratio 1.60, 95% CI 1.16-2.20). Conclusion: Participants reporting frailty experienced nearly twice the risk of medically urgent falls or fractures compared to those who did not report frailty. (C) 2015 S. Karger AG, Basel C1 [Delgado, Cynthia; Shieh, Stephanie; Johansen, Kirsten L.] Univ Calif San Francisco, Nephrol Sect, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Delgado, Cynthia; Shieh, Stephanie; Johansen, Kirsten L.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Grimes, Barbara; Kornak, John] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Chertow, Glenn M.] Stanford Univ, Div Nephrol, Sch Med, Stanford, CA 94305 USA. [Dalrymple, Lorien S.; Kaysen, George A.] Univ Calif Davis, Div Nephrol, Davis, CA 95616 USA. RP Delgado, C (reprint author), San Francisco Dept Vet Affairs, 4150 Clement St,Box 111J, San Francisco, CA 94121 USA. EM cynthia.delgado@ucsf.edu FU National Institutes of Health, National Institute of Diabetes, Digestive and Kidney Disease [N01-DK-7-0005, KD-7-5004]; Department of Veterans Affairs, Clinical Science Research and Development Program under Career Development [1IK2CX000527-01A2]; Department of Veterans Affairs; San Francisco Department of Veterans Affairs Medical Center; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [K23 DK093584]; [1K24DK085153] FX Supported by contract N01-DK-7-0005 and KD-7-5004 from the National Institutes of Health, National Institute of Diabetes, Digestive and Kidney Disease.; Dr. Delgado's work is supported by the Department of Veterans Affairs, Clinical Science Research and Development Program under Career Development Award 1IK2CX000527-01A2. Her contribution is the result of work supported with the resources and the use of facilities at the San Francisco VA Medical Center.; Dr. Shieh's work is supported by the Department of Veterans Affairs, she received fellowship funding support from the San Francisco Department of Veterans Affairs Medical Center. Her contribution is the result of work supported with the resources and the use of facilities at the San Francisco VA Medical Center.; Dr. Johansen is supported by 1K24DK085153 and Dr. Dalrymple is supported by K23 DK093584 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). NR 33 TC 4 Z9 4 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 EI 1421-9670 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2015 VL 42 IS 2 BP 134 EP 140 DI 10.1159/000439000 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA CV0JU UT WOS:000363937800007 PM 26381744 ER PT J AU Kwiatkowski, DJ Wagle, N AF Kwiatkowski, David J. Wagle, Nikhil TI mTOR Inhibitors in Cancer: What Can We Learn from Exceptional Responses? SO EBIOMEDICINE LA English DT Editorial Material ID EVEROLIMUS; SENSITIVITY; MUTATIONS C1 [Kwiatkowski, David J.; Wagle, Nikhil] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Kwiatkowski, David J.; Wagle, Nikhil] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kwiatkowski, David J.; Wagle, Nikhil] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. RP Kwiatkowski, DJ (reprint author), Brigham & Womens Hosp, 1 Blackfan Circle,Room 6-213, Boston, MA 02115 USA. EM dk@rics.bwh.harvard.edu FU NCI NIH HHS [P01 CA120964, CA120964, T32 CA009172] NR 10 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2352-3964 J9 EBIOMEDICINE JI EBioMedicine PD JAN PY 2015 VL 2 IS 1 BP 2 EP 4 DI 10.1016/j.ebiom.2014.12.011 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA CV3JZ UT WOS:000364156800002 PM 26137524 ER PT J AU O'Donnell, E Mahindra, A Yee, AJ Nardi, V Birrer, N Horick, N Borger, D Finkelstein, D Iafrate, JA Raje, N AF O'Donnell, Elizabeth Mahindra, Anuj Yee, Andrew J. Nardi, Valentina Birrer, Nicole Horick, Nora Borger, Darrell Finkelstein, Dianne Iafrate, John A. Raje, Noopur TI Clinical Grade "SNaPshot" Genetic Mutation Profiling in Multiple Myeloma SO EBIOMEDICINE LA English DT Article DE Myeloma; Mutations; Clinical; Therapy; Sequencing ID REFRACTORY MYELOMA; BORTEZOMIB; DEXAMETHASONE; PHASE-2; LENALIDOMIDE; THERAPY AB Whole genome sequencing studies have identified several oncogenic mutations in multiple myeloma (MM). As MM progresses, it evolves genetically underscoring the need to have tools for rapid detection of targetable mutations to optimize individualized treatment. Massachusetts General Hospital (MGH) has developed a Clinical Laboratory Improvement Amendments (CLIA)-approved, high-throughput, genotyping platform to determine the mutation status of a panel of known oncogenes. Sequence analysis using SNaPshot on DNA extracted from bone marrow and extramedullary plasmacytomas is feasible and leads to the detection of potentially druggable mutations. Screening MM patients for somatic mutations in oncogenes may provide novel targets leading to additional therapies for this patient population. (C) 2014 The Authors. Published by Elsevier B.V. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Raje, N (reprint author), Massachusetts Gen Hosp, POB 216,55 Fruit St, Boston, MA 02114 USA. EM nraje@partners.org NR 13 TC 2 Z9 2 U1 3 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2352-3964 J9 EBIOMEDICINE JI EBioMedicine PD JAN PY 2015 VL 2 IS 1 BP 71 EP 73 DI 10.1016/j.ebiom.2014.11.008 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA CV3JZ UT WOS:000364156800015 PM 26137536 ER PT J AU Jain, NG Wong, EA Aranyosi, AJ Boneschansker, L Markmann, JF Briscoe, DM Irimia, D AF Jain, Namrata G. Wong, Elisabeth A. Aranyosi, Alexander J. Boneschansker, Leo Markmann, James F. Briscoe, David M. Irimia, Daniel TI Microfluidic mazes to characterize T-cell exploration patterns following activation in vitro SO INTEGRATIVE BIOLOGY LA English DT Article ID ACUTE ALLOGRAFT-REJECTION; CHEMOKINE RECEPTOR CXCR3; MESSENGER-RNA; MIGRATION; EXPRESSION; CHEMOTAXIS; CD4(+); KIDNEY; MECHANISMS; BEHAVIOR AB The migration of T-cell subsets within peripheral tissues is characteristic of inflammation and immunoregulation. In general, the lymphocyte migratory response is assumed directional and guided by local gradients of chemoattractants and/or chemorepellents. However, little is known about how cells explore their tissue environment, and whether lymphocyte activation may influence speed and exploratory patterns of migration. To probe migration patterns by T-cells we designed a microfluidic maze device that replicates critical features of a tissue-like microenvironment. We quantified the migration patterns of unstimulated and mitogen-activated human T-cells at single cell resolution and found significant differences in exploration within microfluidic mazes. While unstimulated lymphocytes migrated in a directed manner, activated T-cells migrated through large areas of the mazes in an exploratory pattern in response to the chemoattractants RANTES (CCL5) and IP-10 (CXCL10). The analysis of migration enabled by the microfluidic devices help develop new methods for determining how human circulating T-cells function in vivo to seek out antigens in health and disease states. C1 [Jain, Namrata G.; Wong, Elisabeth A.; Aranyosi, Alexander J.; Boneschansker, Leo; Markmann, James F.; Irimia, Daniel] Massachusetts Gen Hosp, Dept Surg, BioMEMS Resource Ctr, Boston, MA 02129 USA. [Jain, Namrata G.; Boneschansker, Leo; Briscoe, David M.] Boston Childrens Hosp, Transplant Res Program, Boston, MA 02115 USA. [Jain, Namrata G.; Boneschansker, Leo; Markmann, James F.; Briscoe, David M.] Boston Childrens Hosp, Dept Med, Div Nephrol, Cambridge, MA 02139 USA. [Jain, Namrata G.; Boneschansker, Leo; Markmann, James F.] Massachusetts Gen Hosp, Dept Surg, Div Transplantat, Boston, MA 02139 USA. [Jain, Namrata G.; Boneschansker, Leo; Markmann, James F.; Briscoe, David M.; Irimia, Daniel] Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Briscoe, DM (reprint author), Boston Childrens Hosp, Transplant Res Program, Boston, MA 02115 USA. EM David.Briscoe@childrens.harvard.edu; dirimia@hms.harvard.edu FU National Institutes of Health (NIH) [GM092804, AI092305]; NIH [T32DK07726] FX We thank Sarah Bruneau and Megan McGourty for support in the isolation of T-cells, FACS analysis and cell culture and Dr Ian Y. Wong for stimulating discussions. Microfabrication was performed at the BioMEMS Resource Center EB002503. This study was supported by National Institutes of Health (NIH) Grants GM092804 (to DI) and by AI092305 (to DMB). NGJ received funding from NIH T32 grant T32DK07726. NR 37 TC 4 Z9 4 U1 0 U2 3 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1757-9694 EI 1757-9708 J9 INTEGR BIOL-UK JI Integr. Biol. PY 2015 VL 7 IS 11 BP 1423 EP 1431 DI 10.1039/c5ib00146c PG 9 WC Cell Biology SC Cell Biology GA CV1PA UT WOS:000364029200008 PM 26325525 ER PT J AU Dubner, L Wang, J Ho, L Ward, L Pasinetti, GM AF Dubner, Lauren Wang, Jun Ho, Lap Ward, Libby Pasinetti, Giulio M. TI Recommendations for Development of New Standardized Forms of Cocoa Breeds and Cocoa Extract Processing for the Prevention of Alzheimer's Disease: Role of Cocoa in Promotion of Cognitive Resilience and Healthy Brain Aging SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Review DE Amyloid; chocolate; diet therapy; Lavado; oligomerization; polyphenols; synapses ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SEED POLYPHENOLIC EXTRACT; MOUSE MODEL; A-BETA; TRANSGENIC MICE; SYNAPTIC DYSFUNCTION; IMPROVES COGNITION; CONTROLLED-TRIAL; TG2576 MICE; RED WINE AB It is currently thought that the lackluster performance of translational paradigms in the prevention of age-related cognitive deteriorative disorders, such as Alzheimer's disease (AD), may be due to the inadequacy of the prevailing approach of targeting only a single mechanism. Age-related cognitive deterioration and certain neurodegenerative disorders, including AD, are characterized by complex relationships between interrelated biological phenotypes. Thus, alternative strategies that simultaneously target multiple underlying mechanisms may represent a more effective approach to prevention, which is a strategic priority of the National Alzheimer's Project Act and the National Institute on Aging. In this review article, we discuss recent strategies designed to clarify the mechanisms by which certain brain-bioavailable, bioactive polyphenols, in particular, flavan-3-ols also known as flavanols, which are highly represented in cocoa extracts, may beneficially influence cognitive deterioration, such as in AD, while promoting healthy brain aging. However, we note that key issues to improve consistency and reproducibility in the development of cocoa extracts as a potential future therapeutic agent requires a better understanding of the cocoa extract sources, their processing, and more standardized testing including brain bioavailability of bioactive metabolites and brain target engagement studies. The ultimate goal of this review is to provide recommendations for future developments of cocoa extracts as a therapeutic agent in AD. C1 [Dubner, Lauren; Wang, Jun; Ho, Lap; Ward, Libby; Pasinetti, Giulio M.] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Wang, Jun; Pasinetti, Giulio M.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Dept Neurol, 1 Gustave L Levy Pl,Box 1137, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu FU National Center for Complementary and Integrative Health (NCCIH) [P50 AT008661-01]; Office of Dietary Supplements (ODS) FX This publication was supported by Grant Number P50 AT008661-01, titled "Dietary Botanicals in the Preservation of Cognitive and Psychological Resilience," from the National Center for Complementary and Integrative Health (NCCIH) and the Office of Dietary Supplements (ODS). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCCIH, ODS, or the National Institutes of Health. NR 67 TC 1 Z9 1 U1 8 U2 17 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2015 VL 48 IS 4 BP 879 EP 889 DI 10.3233/JAD-150536 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CU9LZ UT WOS:000363867300001 PM 26402120 ER PT J AU Alegret, M Rodriguez, O Espinosa, A Ortega, G Sanabria, A Valero, S Hernandez, I Rosende-Roca, M Vargas, L Abdelnour, C Mauleon, A Gailhajanet, A Martin, E Tarraga, L Rentz, DM Amariglio, RE Ruiz, A Boada, M AF Alegret, Montserrat Rodriguez, Octavio Espinosa, Ana Ortega, Gemma Sanabria, Angela Valero, Sergi Hernandez, Isabel Rosende-Roca, Maitee Vargas, Liliana Abdelnour, Carla Mauleon, Ana Gailhajanet, Anna Martin, Elvira Tarraga, Lluis Rentz, Dorene M. Amariglio, Rebecca E. Ruiz, Agustin Boada, Merce TI Concordance between Subjective and Objective Memory Impairment in Volunteer Subjects SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Episodic memory; FNAME; neuropsychology; preclinical Alzheimer's disease; subjective memory impairment ID MILD COGNITIVE IMPAIRMENT; NORMAL OLDER INDIVIDUALS; MINI-MENTAL STATE; ALZHEIMERS-DISEASE; HEALTHY-ADULTS; AMYLOID BURDEN; NORMATIVE DATA; FOLLOW-UP; COMPLAINTS; DEMENTIA AB BACKGROUND: Subjective memory impairment (SMI) refers to subjective awareness of initial memory decline undetectable with existing standardized cognitive tests. The Face Name Associative Memory Exam (FNAME) was created to detect memory deficits in individuals with preclinical Alzheimer's disease (AD). We reported normative data of a Spanish version of FNAME (S-FNAME) in cognitively normal (CN) Spanish-speaking subjects >49. OBJECTIVE: To determine whether higher SMI [a modification of Memory Failures Everyday (MFE-30)] was related to worse memory performance (S-FNAME) or associated with greater affective symptoms in subjects >49; and whether MFE-30 and FNAME were able to discriminate between CN and mild cognitive impairment (MCI) subjects. METHODS: 317 subjects (CN = 196, MCI = 121) were included in the analysis because they attended the annual "Open House Initiative" at Memory Clinic Fundacio ACE, were >49 years, literate, received S-FNAME, MFE-30, and Hospital Anxiety and Depression Scale, had Mini-Mental State Examination scores >= 27, and returned to complete a comprehensive diagnostic assessment. RESULTS: MFE-30 scores were associated with affective symptoms but not with S-FNAME performance. S-FNAME scores were related to performance on memory variables of NBACE (neuropsychological battery used in Fundacio ACE). Although the MCI group showed significantly higher MFE-30 and worse S-FNAME scores than the CN group, their discriminability values were similar (Sensitivity: 49.6 versus 52.9; Specificity: 85.1 versus 83.6, respectively). CONCLUSIONS: SMI was more related to depressive symptoms than to S-FNAME memory performance; and S-FNAME scores were related to other episodic memory test performances, but neither to affective symptoms nor to SMI. MFE-30 and S-FNAME are not optimal for discriminating between CN and MCI groups. Longitudinal follow-up will determine if lower S-FNAME and higher SMI are related to increased risk of AD. C1 [Alegret, Montserrat; Rodriguez, Octavio; Espinosa, Ana; Ortega, Gemma; Sanabria, Angela; Valero, Sergi; Hernandez, Isabel; Rosende-Roca, Maitee; Vargas, Liliana; Abdelnour, Carla; Mauleon, Ana; Gailhajanet, Anna; Martin, Elvira; Tarraga, Lluis; Ruiz, Agustin; Boada, Merce] Fundacio ACE, Alzheimer Res Ctr, Inst Catala Neurociencies Aplicades, Barcelona 08028, Spain. [Alegret, Montserrat; Rodriguez, Octavio; Espinosa, Ana; Ortega, Gemma; Sanabria, Angela; Valero, Sergi; Hernandez, Isabel; Rosende-Roca, Maitee; Vargas, Liliana; Abdelnour, Carla; Mauleon, Ana; Gailhajanet, Anna; Martin, Elvira; Tarraga, Lluis; Ruiz, Agustin; Boada, Merce] Fundacio ACE, Memory Clin, Inst Catala Neurociencies Aplicades, Barcelona 08028, Spain. [Valero, Sergi] Univ Autonoma Barcelona, Hosp Univ Vall dHebron, CIBERSAM, Dept Psychiat, E-08193 Barcelona, Spain. [Rentz, Dorene M.; Amariglio, Rebecca E.] Brigham & Womens Hosp, Dept Neurol, Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. [Rentz, Dorene M.; Amariglio, Rebecca E.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Alegret, M (reprint author), Fundacio ACE, Inst Catala Neurociencies Aplicades, C Gran Via Carles 3,85 Bis, Barcelona 08028, Spain. EM malegret@fundacioace.com FU Araclon Biotech; Grifols; Piramal; Spanish Ministry of Health from Instituto de Salud Carlos III (Madrid) [FISS PI10/00945, PI13/02434]; Agencia d'Avaluacio de Tecnologia i Recerca Mediques; Fundacio ACE Memory Clinic; Fundacio ACE, Institut Catala de Neurociencies Aplicades FX This work was funded by Araclon Biotech, Grifols, Piramal and Fundacio ACE Memory Clinic, and was supported by the Spanish Ministry of Health from Instituto de Salud Carlos III (Madrid) (FISS PI10/00945; PI13/02434) and by the Agencia d'Avaluacio de Tecnologia i Recerca Mediques. Departament de Salut de la Generalitat de Catalunya (Health Department of the Catalan Government) (390) and by funds from Fundacio ACE, Institut Catala de Neurociencies Aplicades. Fundacio ACE is grateful to Mrs. Trinitat Port for her legacy to support our research. Fundacio ACE collaborates with the Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, Spain). NR 55 TC 1 Z9 1 U1 2 U2 7 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2015 VL 48 IS 4 BP 1109 EP 1117 DI 10.3233/JAD-150594 PG 9 WC Neurosciences SC Neurosciences & Neurology GA CU9LZ UT WOS:000363867300022 PM 26444795 ER PT J AU Manchikanti, L Hirsch, JA AF Manchikanti, Laxmaiah Hirsch, Joshua A. TI What can be done about the increasing prevalence of low back pain and associated comorbid factors? SO PAIN MANAGEMENT LA English DT Editorial Material DE chronic low back pain; comorbid factors; disability; economic impact; ergonomics; formative stage; prevention; risk factors ID HEALTH; EPIDEMIOLOGY; PREDICTORS; BURDEN; ADULTS C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY 42003 USA. [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Manchikanti, L (reprint author), Pain Management Ctr Paducah, 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 20 TC 1 Z9 1 U1 0 U2 4 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1758-1869 EI 1758-1877 J9 PAIN MANAG JI Pain Manag. PY 2015 VL 5 IS 3 BP 149 EP 152 DI 10.2217/PMT.15.10 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA CV3KX UT WOS:000364159200001 PM 25971636 ER PT J AU Manchikanti, L Hirsch, JA AF Manchikanti, Laxmaiah Hirsch, Joshua A. TI An update on the management of chronic lumbar discogenic pain SO PAIN MANAGEMENT LA English DT Review DE behavioral therapy; chronic lumbar discogenic pain; epidural injections; intradiscal therapies; lumbar disc replacement; lumbar fusion; lumbar provocation discography; multidisciplinary rehabilitation; physical rehabilitation ID LOW-BACK-PAIN; DEGENERATIVE DISC DISEASE; RANDOMIZED-CONTROLLED-TRIALS; INTERLAMINAR EPIDURAL INJECTIONS; CHRONIC NONCANCER PAIN; INTERVERTEBRAL-DISC; FUSION SURGERY; SPINAL-FUSION; DOUBLE-BLIND; FOLLOW-UP AB Lumbar degenerative disc disease without disc herniation, also known as discogenic pain, is an elusive diagnosis of chronic low back pain. Lumbar provocation discography and fusion surgery have been frequently utilized for several decades as the gold standards for the diagnosis and treatment of symptomatic lumbar discogenic pain, though controversial, based on conjecture, rather than evidence. In addition to lumbar fusion, various other operative and nonoperative modalities of treatments are available in managing chronic lumbar discogenic pain. This review provides an updated assessment of the management of chronic lumbar discogenic pain with a critical look at the many modalities of treatments that are currently available. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY 42003 USA. [Manchikanti, Laxmaiah] Univ Louisville, Dept Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Hirsch, Joshua A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, NeuroIntervent Serv & Neuroendovasc Program, Boston, MA 02114 USA. RP Manchikanti, L (reprint author), Pain Management Ctr Paducah, Paducah, KY 42003 USA. EM drlm@thepainmd.com NR 88 TC 3 Z9 3 U1 0 U2 3 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1758-1869 EI 1758-1877 J9 PAIN MANAG JI Pain Manag. PY 2015 VL 5 IS 5 BP 373 EP 386 DI 10.2217/PMT.15.33 PG 14 WC Clinical Neurology SC Neurosciences & Neurology GA CV3LF UT WOS:000364160000007 PM 26255722 ER PT J AU Berry, DL Blonquist, TM Hong, FX Halpenny, B Partridge, AH AF Berry, Donna L. Blonquist, Traci M. Hong, Fangxin Halpenny, Barbara Partridge, Ann H. TI Self-reported adherence to oral cancer therapy: relationships with symptom distress, depression, and personal characteristics SO PATIENT PREFERENCE AND ADHERENCE LA English DT Article DE patient-centered technology; self-management; logistic regression; recursive partitioning ID ANTICANCER AGENTS; CHEMOTHERAPY; NONADHERENCE; VALIDITY AB Background: Therapeutic cancer chemotherapy is most successful when complete dosing is achieved. Because many newer therapeutic agents are oral and self-administered by the patient, adherence is a concern. The purpose of our analysis was to explore relationships between adherence, patient characteristics, and barriers to adherence. Methods: This secondary analysis utilized self-reported data from a randomized trial of self-care management conducted at two cancer centers in the US. Symptom distress was measured using the 15-item Symptom Distress Scale (SDS-15) and depression with the Patient Health Questionnaire-9 (PHQ-9). Adherence to oral medication was self-reported using the 8-item Morisky Medication Adherence Scale (MMAS-8). Measures were collected via Web-based, study-specific software similar to 8 weeks after treatment start date. Odds of low/medium adherence (score,8) were explored using univariate logistic regression. Given the number of factors and possible relationships among factors, a classification tree was built in lieu of a multivariable logistic regression model. Results: Of the eligible participants enrolled, 77 were on oral therapy and 70 had an MMAS score. Forty-nine (70%) reported a high adherence score (=8). Higher odds of low/medium adherence were associated with greater symptom distress (P=0.09), more depression (P=0.05), chemotherapy vs hormonal oral medication (P=0.03), being female (P=0.02), and being randomized to the control group in the parent trial (P=0.09). Conversely, high adherence was associated with working (P=0.08), being married/partnered (P=0.004), and being older (P=0.02). Factors identified as significantly related to low/medium adherence from the univariate logistic regression analyses were supported by the classification tree results. Conclusion: Nonadherence to therapeutic oral medications in patients with cancer was associated with being unmarried/unpartnered, symptom distress, younger age, not working, and female sex. These findings may help to identify patients at risk for nonadherence and for whom supportive interventions to enhance adherence may be needed. C1 [Berry, Donna L.; Halpenny, Barbara] Dana Farber Canc Inst, Phyllis F Cantor Ctr, Boston, MA 02115 USA. [Berry, Donna L.; Partridge, Ann H.] Dana Farber Canc Inst, Dept Med, Med Oncol, Boston, MA 02115 USA. [Berry, Donna L.; Partridge, Ann H.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Blonquist, Traci M.; Hong, Fangxin] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Hong, Fangxin] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Berry, DL (reprint author), Dana Farber Canc Inst, Phyllis F Cantor Ctr, 450 Brookline Ave,LW 518, Boston, MA 02115 USA. EM donna_berry@dfci.harvard.edu NR 26 TC 1 Z9 1 U1 5 U2 9 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1177-889X J9 PATIENT PREFER ADHER JI Patient Prefer. Adherence PY 2015 VL 9 BP 1587 EP 1592 DI 10.2147/PPA.S91534 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA CV3PV UT WOS:000364172000001 PM 26604712 ER PT B AU Growdon, W Foster, R Rueda, B AF Growdon, Whitfield Foster, Rosemary Rueda, Bo BE DelCarmen, MG Young, RH Schorge, JO Birrer, MJ TI Molecular Targets in Gynecologic Cancers SO UNCOMMON GYNECOLOGIC CANCERS LA English DT Article; Book Chapter ID EPITHELIAL OVARIAN-CANCER; PHASE-II TRIAL; ENDOTHELIAL GROWTH-FACTOR; SQUAMOUS-CELL CARCINOMA; METASTATIC COLORECTAL-CANCER; NEGATIVE BREAST-CANCER; FALLOPIAN-TUBE CANCER; ENDOMETRIOID ENDOMETRIAL CANCER; PRIMARY PERITONEAL CARCINOMA; BEVACIZUMAB PLUS IRINOTECAN C1 [Growdon, Whitfield; Foster, Rosemary; Rueda, Bo] Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. RP Growdon, W (reprint author), Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. NR 202 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 978-1-118-65534-4; 978-1-118-65535-1 PY 2015 BP 3 EP 17 PG 15 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA BD5ZS UT WOS:000361953700002 ER PT B AU del Carmen, MG AF del Carmen, Marcela G. BE DelCarmen, MG Young, RH Schorge, JO Birrer, MJ TI Uncommon Gynecologic Cancers Preface SO UNCOMMON GYNECOLOGIC CANCERS LA English DT Editorial Material; Book Chapter C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA 02138 USA. RP del Carmen, MG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA 02138 USA. NR 0 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 978-1-118-65534-4; 978-1-118-65535-1 PY 2015 BP VIII EP VIII PG 1 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA BD5ZS UT WOS:000361953700001 ER PT B AU Young, RH AF Young, Robert H. BE DelCarmen, MG Young, RH Schorge, JO Birrer, MJ TI Pathology Overview of Rare Gynecologic Tumors SO UNCOMMON GYNECOLOGIC CANCERS LA English DT Article; Book Chapter ID ENDOMETRIAL STROMAL TUMORS; LEYDIG-CELL TUMORS; CLINICOPATHOLOGICAL ANALYSIS; DIFFERENTIAL-DIAGNOSIS; METASTATIC TUMORS; MUCINOUS TUMORS; FALLOPIAN-TUBE; OVARY; CARCINOMA; EMPHASIS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA 02138 USA. RP Young, RH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA 02138 USA. NR 44 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 978-1-118-65534-4; 978-1-118-65535-1 PY 2015 BP 35 EP 49 PG 15 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA BD5ZS UT WOS:000361953700004 ER PT B AU Clark, RM Schorge, JO AF Clark, Rachel M. Schorge, John O. BE DelCarmen, MG Young, RH Schorge, JO Birrer, MJ TI Ovarian Clear Cell Carcinoma SO UNCOMMON GYNECOLOGIC CANCERS LA English DT Article; Book Chapter ID GYNECOLOGIC-ONCOLOGY-GROUP; DISTINCT-HISTOLOGIC-TYPE; INTRAPERITONEAL CISPLATIN; ADJUVANT CHEMOTHERAPY; CLINICAL CHARACTERISTICS; PROGNOSTIC DETERMINANTS; TUMOR PROGRESSION; RANDOMIZED-TRIAL; POOR-PROGNOSIS; PHASE-II C1 [Clark, Rachel M.; Schorge, John O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA 02138 USA. RP Clark, RM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA 02138 USA. NR 62 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 978-1-118-65534-4; 978-1-118-65535-1 PY 2015 BP 53 EP 63 PG 11 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA BD5ZS UT WOS:000361953700005 ER PT B AU del Carmen, MG AF del Carmen, Marcela G. BE DelCarmen, MG Young, RH Schorge, JO Birrer, MJ TI Mucinous Epithelial Ovarian Cancer SO UNCOMMON GYNECOLOGIC CANCERS LA English DT Article; Book Chapter ID GYNECOLOGIC-ONCOLOGY-GROUP; K-RAS MUTATIONS; TERM-FOLLOW-UP; CARCINOEMBRYONIC ANTIGEN; DIFFERENTIAL-DIAGNOSIS; COLORECTAL-CANCER; COLONIC-CARCINOMA; GROUP EXPERIENCE; STAGE-III; PHASE-II C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA 02138 USA. RP del Carmen, MG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA 02138 USA. NR 51 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 978-1-118-65534-4; 978-1-118-65535-1 PY 2015 BP 64 EP 69 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA BD5ZS UT WOS:000361953700006 ER PT B AU Bradford, LS Goodman, A AF Bradford, Leslie S. Goodman, Annekathryn BE DelCarmen, MG Young, RH Schorge, JO Birrer, MJ TI Pseudomyxoma Peritonei SO UNCOMMON GYNECOLOGIC CANCERS LA English DT Article; Book Chapter ID HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY; SYNCHRONOUS MUCINOUS TUMORS; APPENDICEAL ORIGIN; CLINICOPATHOLOGICAL ANALYSIS; CYTOREDUCTIVE SURGERY; OVARIAN-TUMORS; IMMUNOHISTOCHEMICAL EVIDENCE; PATHOLOGICAL FEATURES; VERMIFORM APPENDIX; BORDERLINE TUMORS C1 [Bradford, Leslie S.; Goodman, Annekathryn] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA 02138 USA. RP Bradford, LS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA 02138 USA. NR 63 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 978-1-118-65534-4; 978-1-118-65535-1 PY 2015 BP 70 EP 80 PG 11 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA BD5ZS UT WOS:000361953700007 ER PT B AU Garrett, LA del Carmen, MG AF Garrett, Leslie A. del Carmen, Marcela G. BE DelCarmen, MG Young, RH Schorge, JO Birrer, MJ TI Endometriosis-Associated Ovarian Cancer SO UNCOMMON GYNECOLOGIC CANCERS LA English DT Article; Book Chapter ID CLEAR-CELL CARCINOMA; POSITRON-EMISSION-TOMOGRAPHY; HOSPITAL DISCHARGE DIAGNOSIS; DISTINCT-HISTOLOGIC-TYPE; ESTROGEN-RECEPTOR-ALPHA; EPITHELIAL OVARIAN; MALIGNANT-TRANSFORMATION; ATYPICAL ENDOMETRIOSIS; BREAST-CANCER; EXTRAOVARIAN ENDOMETRIOSIS C1 [Garrett, Leslie A.] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02138 USA. [del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA USA. RP Garrett, LA (reprint author), Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02138 USA. NR 132 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 978-1-118-65534-4; 978-1-118-65535-1 PY 2015 BP 94 EP 108 PG 15 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA BD5ZS UT WOS:000361953700009 ER PT B AU Rauh-Hain, JA del Carmen, MG AF Rauh-Hain, J. Alejandro del Carmen, Marcela G. BE DelCarmen, MG Young, RH Schorge, JO Birrer, MJ TI Carcinosarcoma of the Ovary SO UNCOMMON GYNECOLOGIC CANCERS LA English DT Article; Book Chapter ID MIXED MULLERIAN TUMORS; GYNECOLOGIC-ONCOLOGY-GROUP; PLATINUM-BASED CHEMOTHERAPY; FEMALE GENITAL-TRACT; PROGNOSTIC-FACTORS; MESODERMAL TUMOR; IMMUNOHISTOCHEMICAL ANALYSIS; HISTOGENETIC CONSIDERATIONS; COMBINATION CHEMOTHERAPY; SURGICAL CYTOREDUCTION C1 [Rauh-Hain, J. Alejandro; del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA 02138 USA. RP Rauh-Hain, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA 02138 USA. NR 66 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 978-1-118-65534-4; 978-1-118-65535-1 PY 2015 BP 109 EP 119 PG 11 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA BD5ZS UT WOS:000361953700010 ER PT B AU del Carmen, MG AF del Carmen, Marcela G. BE DelCarmen, MG Young, RH Schorge, JO Birrer, MJ TI Malignant Germ Cell Tumors of the Ovary SO UNCOMMON GYNECOLOGIC CANCERS LA English DT Article; Book Chapter ID GYNECOLOGIC-ONCOLOGY-GROUP; ENDODERMAL SINUS TUMOR; CARBOPLATIN-BASED CHEMOTHERAPY; CISPLATIN-BASED CHEMOTHERAPY; INSTITUT-GUSTAVE-ROUSSY; HIGH-DOSE CHEMOTHERAPY; EARLY-STAGE OVARIAN; 10 YEARS EXPERIENCE; YOLK-SAC TUMORS; SALVAGE THERAPY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA 02138 USA. RP del Carmen, MG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA 02138 USA. NR 74 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 978-1-118-65534-4; 978-1-118-65535-1 PY 2015 BP 120 EP 131 PG 12 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA BD5ZS UT WOS:000361953700011 ER PT B AU del Carmen, MG Penson, RT AF del Carmen, Marcela G. Penson, Richard T. BE DelCarmen, MG Young, RH Schorge, JO Birrer, MJ TI Malignant Sex Cord-Stromal Tumors of the Ovary SO UNCOMMON GYNECOLOGIC CANCERS LA English DT Article; Book Chapter ID GRANULOSA-CELL TUMORS; MULLERIAN-INHIBITING SUBSTANCE; PROGNOSTIC-FACTORS; ALPHA-INHIBIN; CLINICOPATHOLOGICAL ANALYSIS; DICER1 MUTATIONS; FOLLOW-UP; BLEOMYCIN; CISPLATIN; CHEMOTHERAPY C1 [del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA 02138 USA. [Penson, Richard T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Med Oncol, Boston, MA USA. RP del Carmen, MG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA 02138 USA. NR 57 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 978-1-118-65534-4; 978-1-118-65535-1 PY 2015 BP 132 EP 138 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA BD5ZS UT WOS:000361953700012 ER PT B AU Kaphan, AA Castro, CM AF Kaphan, Ariel A. Castro, Cesar M. BE DelCarmen, MG Young, RH Schorge, JO Birrer, MJ TI Small Cell and Neuroendocrine Cancers of the Ovary SO UNCOMMON GYNECOLOGIC CANCERS LA English DT Article; Book Chapter ID HYPERCALCEMIC TYPE; GYNECOLOGIC TRACT; CARCINOMA; EXPERIENCE; MANAGEMENT C1 [Kaphan, Ariel A.; Castro, Cesar M.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02138 USA. [Kaphan, Ariel A.; Castro, Cesar M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Kaphan, AA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02138 USA. NR 26 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 978-1-118-65534-4; 978-1-118-65535-1 PY 2015 BP 139 EP 147 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA BD5ZS UT WOS:000361953700013 ER PT B AU Thaker, PH Dizon, DS AF Thaker, Premal H. Dizon, Don S. BE DelCarmen, MG Young, RH Schorge, JO Birrer, MJ TI Uterine Carcinosarcoma SO UNCOMMON GYNECOLOGIC CANCERS LA English DT Article; Book Chapter ID GYNECOLOGIC-ONCOLOGY-GROUP; MIXED MULLERIAN TUMORS; PHASE-III TRIAL; POTENTIAL THERAPEUTIC TARGETS; TERM TAMOXIFEN TREATMENT; STAGE-I; ENDOMETRIAL-CANCER; PROGNOSTIC-FACTORS; CERVICAL-CARCINOMA; RADIATION-THERAPY C1 [Thaker, Premal H.] Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 USA. [Dizon, Don S.] Massachusetts Gen Hosp, Ctr Canc, Gillette Ctr Gynecol Oncol, Oncol Sexual Hlth, Boston, MA USA. RP Thaker, PH (reprint author), Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 USA. NR 73 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 978-1-118-65534-4; 978-1-118-65535-1 PY 2015 BP 159 EP 166 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA BD5ZS UT WOS:000361953700015 ER PT B AU del Carmen, MG AF del Carmen, Marcela G. BE DelCarmen, MG Young, RH Schorge, JO Birrer, MJ TI Uterine Leiomyosarcoma SO UNCOMMON GYNECOLOGIC CANCERS LA English DT Article; Book Chapter ID GYNECOLOGIC-ONCOLOGY-GROUP; SOFT-TISSUE SARCOMA; SMOOTH-MUSCLE TUMORS; PHASE-II TRIAL; GEMCITABINE PLUS DOCETAXEL; PROGESTERONE-RECEPTOR EXPRESSION; LYMPH-NODE METASTASIS; RENAL-CELL CANCER; PROGNOSTIC-FACTORS; IMMUNOHISTOCHEMICAL ANALYSIS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA 02138 USA. RP del Carmen, MG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA 02138 USA. NR 91 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-65534-4; 978-1-118-65535-1 PY 2015 BP 167 EP 177 PG 11 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA BD5ZS UT WOS:000361953700016 ER PT B AU Clark, RM del Carmen, MG AF Clark, Rachel M. del Carmen, Marcela G. BE DelCarmen, MG Young, RH Schorge, JO Birrer, MJ TI Mucinous Tumors of the Uterine Corpus SO UNCOMMON GYNECOLOGIC CANCERS LA English DT Article; Book Chapter ID GYNECOLOGIC-ONCOLOGY-GROUP; SIMULATING MICROGLANDULAR HYPERPLASIA; PAPILLARY-SEROUS-CARCINOMA; ENDOMETRIAL ADENOCARCINOMA; IMMUNOHISTOCHEMICAL FEATURES; DIFFERENTIAL-DIAGNOSIS; CANCER; THERAPY; EMPHASIS; SURVIVAL C1 [Clark, Rachel M.; del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA 02138 USA. RP Clark, RM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA 02138 USA. NR 47 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 978-1-118-65534-4; 978-1-118-65535-1 PY 2015 BP 178 EP 185 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA BD5ZS UT WOS:000361953700017 ER PT B AU Rauh-Hain, JA Olawaiye, AB Boruta, DM AF Rauh-Hain, J. Alejandro Olawaiye, Alexander B. Boruta, David M. BE DelCarmen, MG Young, RH Schorge, JO Birrer, MJ TI Uterine Clear Cell Carcinoma SO UNCOMMON GYNECOLOGIC CANCERS LA English DT Article; Book Chapter ID GYNECOLOGIC-ONCOLOGY-GROUP; PHASE-III TRIAL; RECURRENT ENDOMETRIAL CARCINOMA; DOXORUBICIN PLUS CISPLATIN; GENE-EXPRESSION PROFILES; HIGH-RISK; RADIATION-THERAPY; STAGE-I; MICROSATELLITE INSTABILITY; 1ST-LINE CHEMOTHERAPY C1 [Rauh-Hain, J. Alejandro; Boruta, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA 02138 USA. [Olawaiye, Alexander B.] Magee Womens Hosp, Div Gynecol Oncol, Pittsburgh, PA USA. RP Rauh-Hain, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA 02138 USA. NR 67 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 978-1-118-65534-4; 978-1-118-65535-1 PY 2015 BP 186 EP 194 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA BD5ZS UT WOS:000361953700018 ER PT B AU Schmeler, KM Rauh-Hain, JA del Carmen, MG AF Schmeler, Kathleen M. Rauh-Hain, J. Alejandro del Carmen, Marcela G. BE DelCarmen, MG Young, RH Schorge, JO Birrer, MJ TI Endometrial Stromal Sarcomas SO UNCOMMON GYNECOLOGIC CANCERS LA English DT Article; Book Chapter ID SMOOTH-MUSCLE DIFFERENTIATION; HIGH-GRADE SARCOMAS; UTERINE SARCOMAS; MESENCHYMAL TUMORS; IMMUNOHISTOCHEMICAL ANALYSIS; GLANDULAR DIFFERENTIATION; OVARIAN PRESERVATION; PULMONARY METASTASES; PROGNOSTIC-FACTORS; HORMONAL TREATMENT C1 [Schmeler, Kathleen M.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. [Rauh-Hain, J. Alejandro; del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA USA. RP Schmeler, KM (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. NR 102 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 978-1-118-65534-4; 978-1-118-65535-1 PY 2015 BP 205 EP 216 PG 12 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA BD5ZS UT WOS:000361953700020 ER PT B AU Foley, OW Bradford, LS del Carmen, MG AF Foley, Olivia W. Bradford, Leslie S. del Carmen, Marcela G. BE DelCarmen, MG Young, RH Schorge, JO Birrer, MJ TI Small Cell Neuroendocrine Carcinoma of the Cervix SO UNCOMMON GYNECOLOGIC CANCERS LA English DT Article; Book Chapter ID UTERINE CERVIX; LUNG-CANCER; PROGNOSTIC-FACTORS; HUMAN-PAPILLOMAVIRUS; ENDOCRINE TUMORS; COMBINATION CHEMOTHERAPY; ADJUVANT CHEMOTHERAPY; SINGLE INSTITUTION; GYNECOLOGIC TRACT; DOXORUBICIN C1 [Foley, Olivia W.; Bradford, Leslie S.; del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA 02138 USA. RP Foley, OW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA 02138 USA. NR 52 TC 0 Z9 0 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, WEST SUSSEX, ENGLAND BN 978-1-118-65534-4; 978-1-118-65535-1 PY 2015 BP 219 EP 227 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA BD5ZS UT WOS:000361953700021 ER PT B AU Clark, RM Rauh-Hain, JA del Carmen, MG AF Clark, Rachel M. Rauh-Hain, J. Alejandro del Carmen, Marcela G. BE DelCarmen, MG Young, RH Schorge, JO Birrer, MJ TI Sarcomas of the Vulva and Vagina SO UNCOMMON GYNECOLOGIC CANCERS LA English DT Article; Book Chapter ID FEMALE GENITAL-TRACT; SOFT-TISSUE SARCOMA; SMOOTH-MUSCLE TUMORS; AGGRESSIVE ANGIOMYXOMA; DERMATOFIBROSARCOMA PROTUBERANS; INTERSTITIAL BRACHYTHERAPY; CONSERVATIVE TREATMENT; EPITHELIOID SARCOMA; SYNOVIAL SARCOMA; ANGIOSARCOMA C1 [Clark, Rachel M.; Rauh-Hain, J. Alejandro; del Carmen, Marcela G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA 02138 USA. RP Clark, RM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gynecol Oncol,Vincent Obstet & Gynecol, Boston, MA 02138 USA. NR 49 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 978-1-118-65534-4; 978-1-118-65535-1 PY 2015 BP 236 EP 244 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA BD5ZS UT WOS:000361953700023 ER PT B AU Growdon, W AF Growdon, Whitfield BE DelCarmen, MG Young, RH Schorge, JO Birrer, MJ TI Gestational Trophoblastic Disease SO UNCOMMON GYNECOLOGIC CANCERS LA English DT Article; Book Chapter ID COMPLETE HYDATIDIFORM MOLE; CENTRAL-NERVOUS-SYSTEM; GYNECOLOGIC-ONCOLOGY-GROUP; AGENT METHOTREXATE CHEMOTHERAPY; RETROSPECTIVE COHORT SURVEY; UNDETECTABLE HCG LEVELS; EMA-CO CHEMOTHERAPY; FREE BETA-SUBUNIT; PHASE-II TRIAL; LOW-RISK C1 Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Growdon, W (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 117 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 978-1-118-65534-4; 978-1-118-65535-1 PY 2015 BP 245 EP 259 PG 15 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA BD5ZS UT WOS:000361953700024 ER PT S AU Hooper, DC Jacoby, GA AF Hooper, David C. Jacoby, George A. BE Wright, GD TI Mechanisms of drug resistance: quinolone resistance SO ANTIMICROBIAL THERAPEUTICS REVIEWS SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE topoisomerase; efflux pumps; plasmids; quinolone; DNA gyrase ID MULTIDRUG EFFLUX PUMP; SPECTRUM-BETA-LACTAMASE; MULTIPLE ANTIBIOTIC-RESISTANCE; FOOD-PRODUCING ANIMALS; COMPLETE NUCLEOTIDE-SEQUENCE; 16S RIBOSOMAL-RNA; MEXA-MEXB-OPRM; CIPROFLOXACIN-MODIFYING ENZYME; ENTERICA SEROVAR TYPHIMURIUM; PENTAPEPTIDE REPEAT PROTEINS AB Quinolone antimicrobials are synthetic and widely used in clinical medicine. Resistance emerged with clinical use and became common in some bacterial pathogens. Mechanisms of resistance include two categories of mutation and acquisition of resistance-conferring genes. Resistance mutations in one or both of the two drug target enzymes, DNA gyrase and DNA topoisomerase IV, are commonly in a localized domain of the GyrA and ParE subunits of the respective enzymes and reduce drug binding to the enzyme DNA complex. Other resistance mutations occur in regulatory genes that control the expression of native efflux pumps localized in the bacterial membrane(s). These pumps have broad substrate profiles that include quinolones as well as other antimicrobials, disinfectants, and dyes. Mutations of both types can accumulate with selection pressure and produce highly resistant strains. Resistance genes acquired on plasmids can confer low-level resistance that promotes the selection of mutational high-level resistance. Plasmid-encoded resistance is due to Qnr proteins that protect the target enzymes from quinolone action, one mutant aminoglycoside-modifying enzyme that also modifies certain quinolones, and mobile efflux pumps. Plasmids with these mechanisms often encode additional antimicrobial resistances and can transfer multidrug resistance that includes quinolones. Thus, the bacterial quinolone resistance armamentarium is large. C1 [Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Jacoby, George A.] Lahey Hosp & Med Ctr, Burlington, MA USA. [Hooper, David C.; Jacoby, George A.] Harvard Univ, Sch Med, Boston, MA USA. RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@mgh.harvard.edu FU NIAID NIH HHS [P01 AI083214, R01 AI023988, R01 AI057576, R37 AI023988] NR 242 TC 22 Z9 23 U1 9 U2 26 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 2015 VL 1354 BP 12 EP 31 DI 10.1111/nyas.12830 PG 20 WC Infectious Diseases; Pharmacology & Pharmacy SC Infectious Diseases; Pharmacology & Pharmacy GA BD7WC UT WOS:000363636000002 PM 26190223 ER PT J AU Hwang, J Hwang, TJ Ciolino, JB AF Hwang, Jenny Hwang, Thomas J. Ciolino, Joseph B. TI Pivotal clinical trials of novel ophthalmic drugs and medical devices: retrospective observational study, 2002-2012 SO BMJ OPEN LA English DT Article ID CARDIOVASCULAR DEVICES; APPROVAL; SAFETY; FDA; SURVEILLANCE; ORPHAN; AGE AB Objectives: Novel therapeutics are an important part of ophthalmologists' armamentarium, and the risks and benefits of these therapies must be carefully evaluated. We sought to quantify the characteristics of the pivotal clinical trials supporting the regulatory approval of new ophthalmic drugs and medical devices. Design: Retrospective observational study. Setting and data source: Medical review dossiers for new ophthalmic drug and high-risk device approvals released publicly by the US Food and Drug Administration (FDA). Main outcome measures: Proportion of pivotal trials with randomisation, masking, active or placebo controls and subgroup analyses; total and median number of trial enrollees; and the number of drugs and devices approved with required postapproval studies. Results: From 2002 to 2012, the FDA approved 11 ophthalmic drugs and 25 devices. The pivotal trials underlying the approvals of ophthalmic drugs in our study cohort enrolled a median of 809 patients. Virtually all drug trials were randomised and masked (91%), of which 7 (70%) used a placebo control. Pivotal trials for ophthalmic devices enrolled 324 patients on average, and significantly fewer trials for ophthalmic devices versus drugs were randomised (16% vs 91%; p<0.001) or masked (12% vs 91%; p<0.001). 8 (32%) ophthalmic devices and 6 (55%) ophthalmic drugs were approved with required postapproval studies. Conclusions: Ophthalmic therapeutics were approved based on varying levels of evidence. Postapproval studies could be used to confirm or refute early indications of safety and effectiveness of these therapeutics, with the study results accessible to patients and clinicians who need to make informed treatment decisions. C1 [Hwang, Jenny] St Johns Riverside Hosp, Yonkers, NY 10701 USA. [Hwang, Thomas J.] Harvard Univ, Fac Arts & Sci, Cambridge, MA 02138 USA. [Hwang, Thomas J.] Blackstone Grp, London, England. [Ciolino, Joseph B.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Hwang, TJ (reprint author), St Johns Riverside Hosp, Yonkers, NY 10701 USA. EM tjhwang@post.harvard.edu FU Career Development Award from Research to Prevent Blindness, Inc, New York; National Institute of Health/National Eye Institute [K08EY019686] FX JBC is supported by a Career Development Award from Research to Prevent Blindness, Inc, New York, and the National Institute of Health/National Eye Institute (K08EY019686). NR 44 TC 2 Z9 2 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 2015 VL 5 IS 6 AR e007987 DI 10.1136/bmjopen-2015-007987 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA CU4EO UT WOS:000363479900087 PM 26044760 ER PT J AU Jackson, R Shiozawa, A Buysman, EK Altan, A Korrer, S Choi, H AF Jackson, Robert Shiozawa, Aki Buysman, Erin K. Altan, Aylin Korrer, Stephanie Choi, Hyon TI Flare frequency, healthcare resource utilisation and costs among patients with gout in a managed care setting: a retrospective medical claims-based analysis SO BMJ OPEN LA English DT Article ID COMMERCIALLY INSURED POPULATION; ECONOMIC BURDEN; SERUM URATE; ARTHRITIS ATTACKS; HYPERURICEMIA; OUTCOMES AB Objectives: For most gout patients, excruciatingly painful gout attacks are the major clinical burden of the disease. The goal of this study was to assess the association of frequent gout flares with healthcare burden, and to quantify how much lower gout-related costs and resource use are for those with infrequent flares compared to frequent gout flares. Design: Retrospective cohort study. Setting: Administrative claims data from a large US health plan. Participants: Patients aged 18 years or above, and with evidence of gout based on medical and pharmacy claims between January 2009 and April 2012 were eligible for inclusion. Patient characteristics were assessed during a 12-month baseline period. Outcome measures: Frequency of gout flares, healthcare costs and resource utilisation were assessed in the 12 months following the first qualifying gout claim. Generalised linear models were employed to assess the impact of flare frequency on cost outcomes after adjusting for covariates. Results: 102 703 patients with gout met study inclusion criteria; 89 201 had 0-1 gout flares, 9714 had 2 flares, and 3788 had 3+ flares. Average counts of gout-related inpatient stays, emergency room visits and ambulatory visits were higher among patients with 2 or 3+ flares, compared to those with 0-1 flares (all p<0.001). Adjusted annual gout-related costs were $1804, $3014 and $4363 in those with 0-1, 2 and 3+ gout flares, respectively (p<0.001 comparing 0-1 flares to 2 or 3+ flares). Conclusions: Gout-related costs and resource use were lower for those with infrequent flares, suggesting significant cost benefit to a gout management plan that has a goal of reducing flare frequency. C1 [Jackson, Robert; Shiozawa, Aki] Takeda Pharmaceut Int Inc, Deerfield, IL 60015 USA. [Buysman, Erin K.; Altan, Aylin; Korrer, Stephanie] Optum, Eden Prairie, MN USA. [Choi, Hyon] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Shiozawa, A (reprint author), Takeda Pharmaceut Int Inc, Deerfield, IL 60015 USA. EM aki.shiozawa@takeda.com RI Shiozawa, Aki/O-2443-2014 OI Shiozawa, Aki/0000-0001-9757-6337 FU Takeda Pharmaceuticals International, Inc. FX This study was sponsored by Takeda Pharmaceuticals International, Inc. NR 22 TC 3 Z9 3 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 2015 VL 5 IS 6 AR e007214 DI 10.1136/bmjopen-2014-007214 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CU4EO UT WOS:000363479900039 PM 26109113 ER PT J AU Reed, N Greenspoon, D Iverson, GL DeMatteo, C Fait, P Gauvin-Lepage, J Hunt, A Gagnon, IJ AF Reed, Nick Greenspoon, Dayna Iverson, Grant L. DeMatteo, Carol Fait, Philippe Gauvin-Lepage, Jerome Hunt, Anne Gagnon, Isabelle J. TI Management of persistent postconcussion symptoms in youth: a randomised control trial protocol SO BMJ OPEN LA English DT Article ID TRAUMATIC BRAIN-INJURY; SPORT-RELATED CONCUSSION; GENERIC CORE SCALES; PREADOLESCENT CHILDREN; PHYSICAL-ACTIVITY; AEROBIC FITNESS; RELIABILITY; PERFORMANCE; EXERCISE; VALIDITY AB Introduction: Current management of concussion consists of early education, rest until symptom free, with gradual return to school and physical activity protocols. Although this management strategy is effective for most youth who sustain a concussion, it is not an appropriate strategy for youth with persistent postconcussion symptoms. Prolonged rest and periods of restricted activity may place youth at risk for secondary issues and contribute to the chronicity of postconcussion symptoms. The purpose of this study is to evaluate the efficacy of an active rehabilitation protocol for youth who are slow to recover from concussion. It is hypothesised that an active rehabilitation intervention can reduce persistent postconcussion symptoms, improve function and facilitate return to activity. This article describes the research protocol. Methods and analysis: This is a randomised clinical trial with blinded outcome measurement. Participants will be recruited and randomly assigned to 1 of 2 treatment groups, an active rehabilitation intervention or a standard care education group. Both groups will receive standard care education. However, the active rehabilitation group will participate in an additional low-intensity exercise programme consisting of aerobic, coordination and visualisation exercises. Both the active rehabilitation and the standard care education interventions will be 6 weeks in duration. The primary outcome measure is postconcussion symptoms. Secondary outcome measures include functional recovery (cognitive, motor, psychosocial and emotional functioning) and return to activity. Outcome measures will be administered preintervention and postintervention. The primary outcome measure will also be repeated 2 weeks into the intervention period. Ethics and dissemination: This study has been approved by the Holland Bloorview Kids Rehabilitation Hospital research ethics board (REB # 13-459). The findings from this study will be shared with the general public, sport associations, relevant brain injury organisations and healthcare professionals. C1 [Reed, Nick; Hunt, Anne] Holland Bloorview Kids Rehabil Hosp, Bloorview Res Inst, Concuss Res Ctr, Toronto, ON, Canada. [Reed, Nick] Univ Toronto, Dept Occupat Sci & Occupat Therapy, Toronto, ON, Canada. [Greenspoon, Dayna] Holland Bloorview Kids Rehabil Hosp, Bloorview Res Inst, Concuss Res Ctr, Ctr Leadership ABI, Toronto, ON, Canada. [Iverson, Grant L.] Harvard Univ, Dept Phys Med & Rehabil, Sch Med, Boston, MA USA. [Iverson, Grant L.] Spaulding Rehabil Hosp, Boston, MA USA. [Iverson, Grant L.] MassGen Hosp Children Sports Concuss Program, Boston, MA USA. [Iverson, Grant L.] Red Sox Fdn, Boston, MA USA. [Iverson, Grant L.] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA. [DeMatteo, Carol] McMaster Univ, Sch Rehabil Sci, Hamilton, ON, Canada. [DeMatteo, Carol] CanChild Ctr Childhood Disabil Res, Hamilton, ON, Canada. [Fait, Philippe] Univ Quebec Trois Rivieres, Dept Human Kinet Sci, Trois Rivieres, PQ GA9 5H7, Canada. [Fait, Philippe] UQTR, Res Grp Neuromusculoskeletal Dysfunct, Trois Rivieres, PQ, Canada. [Fait, Philippe] Ctr Rech Neuropsychol, Montreal, PQ, Canada. [Fait, Philippe] Clin Cortex Med & Readaptat, Quebec City, PQ, Canada. [Gauvin-Lepage, Jerome] McGill Univ, Sch Phys & Occupat Therapy, Montreal, PQ, Canada. [Gagnon, Isabelle J.] McGill Univ, Sch Phys & Occupat Therapy, Fac Med, Montreal, PQ, Canada. [Gagnon, Isabelle J.] McGill Univ, Montreal Childrens Hosp, Ctr Hlth, Trauma, Montreal, PQ H3H 1P3, Canada. RP Reed, N (reprint author), Holland Bloorview Kids Rehabil Hosp, Bloorview Res Inst, Concuss Res Ctr, Toronto, ON, Canada. EM nreed@hollandbloorview.ca RI Meijer, Anna/K-5118-2016 FU Fonds de recherche du Quebec-Sante FX Funding for the pilot study informing this protocol was provided by Fonds de recherche du Quebec-Sante. NR 39 TC 1 Z9 1 U1 4 U2 14 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 2015 VL 5 IS 7 AR e008468 DI 10.1136/bmjopen-2015-008468 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CU4FH UT WOS:000363482000073 PM 26231756 ER PT J AU Tan, ASL Bigman, CA Mello, S Sanders-Jackson, A AF Tan, Andy S. L. Bigman, Cabral A. Mello, Susan Sanders-Jackson, Ashley TI Is exposure to e-cigarette communication associated with perceived harms of e-cigarette secondhand vapour? Results from a national survey of US adults SO BMJ OPEN LA English DT Article ID NICOTINE DELIVERY-SYSTEMS; ELECTRONIC CIGARETTES; SMOKING-CESSATION; MASS-MEDIA; INTERPERSONAL-COMMUNICATION; NONCOMBUSTIBLE TOBACCO; YOUNG-ADULTS; DONT TRUST; PERCEPTIONS; RISK AB Objectives: E-cigarettes are frequently advertised and portrayed in the media as less harmful compared with regular cigarettes. Earlier surveys reported public perceptions of harms to people using e-cigarettes; however, public perceptions of harms from exposure to secondhand vapour (SHV) have not been studied. We examined associations between self-reported exposure to e-cigarette advertising, media coverage, and interpersonal discussion and perceived harms of SHV. Design: Observational study. Setting: National online sample of US adults aged >= 18 years. Participants: 1449 US adults (mean age 49.5 years), 51.3% female, 76.6% non-Hispanic Caucasian, 7.5% African-American, 10.0% Hispanic and 5.9% other races. Outcomes: Perceived harm measures included (1) harmfulness of SHV to one's health, (2) concern about health impact of breathing SHV and (3) comparative harm of SHV versus secondhand smoke (SHS). Predictors were (1) self-reported frequency of exposure to e-cigarette advertising, media coverage and interpersonal discussion (close friends or family) and (2) perceived valence of exposure from each source. Covariates were demographic characteristics, cigarette smoking status and e-cigarette use, and were weighted to the general US adult population. Results: More frequent interpersonal discussion was associated with lower perceived harmfulness of SHV to one's health and lower perceived comparative harm of SHV versus SHS. Frequency of e-cigarette ad and other media exposure were not significant predictors. Perceived negative valence of ad exposure and interpersonal discussion (vs no exposure) was associated with higher perceived harm across all three outcomes, while negative valence of media coverage was associated with higher concern about health impact of breathing SHV. Perceived positive valence (vs no exposure) of interpersonal discussion was associated with lower perceived harm across all three outcomes about health impact of breathing SHV. Conclusions: Exposure to information about e-cigarettes through advertising, media coverage and interpersonal discussion could play a role in shaping public perceptions of the harmfulness of SHV. C1 [Tan, Andy S. L.] Dana Farber Canc Inst, Ctr Community Based Res, Div Populat Sci, Boston, MA 02115 USA. [Tan, Andy S. L.] Harvard TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA USA. [Bigman, Cabral A.] Univ Illinois, Dept Commun, Urbana, IL 61801 USA. [Mello, Susan] Northeastern Univ, Dept Commun Studies, Boston, MA 02115 USA. [Sanders-Jackson, Ashley] Stanford Univ, Stanford Prevent Res Ctr, Stanford, CA 94305 USA. RP Tan, ASL (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, Div Populat Sci, Boston, MA 02115 USA. EM andy_tan@dfci.harvard.edu FU National Heart, Lung, and Blood Institute [T32HL007034]; National Cancer Institute [P20CA095856] FX Data for this research came from the Annenberg National Health Communication Survey, supported by the Annenberg School at the University of Pennsylvania and the University of Southern California. ASLT conducted this work while a postdoctoral fellow at the Center of Excellence in Cancer Communication Research at the University of Pennsylvania and later an assistant professor at the Dana-Farber Cancer Institute and Harvard School of Public Health. CAB conducted this work while an assistant professor at the University of Illinois at Urbana-Champaign. SM conducted this work while an assistant professor at Northeastern University. AS-J conducted this work while a postdoctoral fellow at Stanford Prevention Research Center. This work was supported by National Heart, Lung, and Blood Institute grant number T32HL007034 and National Cancer Institute grant number P20CA095856. NR 50 TC 8 Z9 8 U1 2 U2 6 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 2015 VL 5 IS 3 AR e007134 DI 10.1136/bmjopen-2014-007134 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CU3WZ UT WOS:000363458200074 PM 25814497 ER PT J AU Tsugawa, Y Hasegawa, K Hiraide, A Jha, AK AF Tsugawa, Yusuke Hasegawa, Kohei Hiraide, Atsushi Jha, Ashish K. TI Regional health expenditure and health outcomes after out-of-hospital cardiac arrest in Japan: an observational study SO BMJ OPEN LA English DT Article ID AMERICAN-HEART-ASSOCIATION; CARE; POPULATION; SURVIVAL; UPDATE; MODELS AB Objectives: Japan is considering policies to set the target health expenditure level for each region, a policy approach that has been considered in many other countries. The objective of this study was to examine the relationship between regional health expenditure and health outcomes after out-of-hospital cardiac arrest (OHCA), which incorporates the qualities of prehospital, in-hospital and posthospital care systems. Design: We examined the association between prefecture-level per capita health expenditure and patients' health outcomes after OHCA. Setting: We used a nationwide, population-based registry system of OHCAs that captured all cases with OHCA resuscitated by emergency responders in Japan from 2005 to 2011. Participants: All patients with OHCA aged 1-100 years were analysed. Outcome measures: The patients' 1-month survival rate, and favourable neurological outcome (defined as cerebral performance category 1-2) at 1-month. Results: Among 618 154 cases with OHCA, the risk-adjusted 1-month survival rate varied from 3.3% (95% CI 2.9% to 3.7%) to 8.4% (95% CI 7.7% to 9.1%) across prefectures. The risk-adjusted probabilities of favourable neurological outcome ranged from 1.6% (95% CI 1.4% to 1.9%) to 3.7% (95% CI 3.4% to 3.9%). Compared with prefectures with lowest tertile health expenditure, 1-month survival rate was significantly higher in medium-spending (adjusted OR 1.31, 95% CI 1.03 to 1.66, p= 0.03) and high-spending prefectures (adjusted OR 1.30, 95% CI 1.03 to 1.64, p= 0.02), after adjusting for patient characteristics. There was no difference in the survival between medium-spending and high-spending regions. We observed similar patterns for favourable neurological outcome. Additional adjustment for regional per capita income did not affect our overall findings. Conclusions: We observed a wide variation in the health outcomes after OHCA across regions. Low-spending regions had significantly worse health outcomes compared with medium-spending or high-spending regions, but no difference was observed between medium-spending and high-spending regions. Our findings suggest that focusing on the median spending may be the optimum that allows for saving money without compromising patient outcomes. C1 [Tsugawa, Yusuke; Jha, Ashish K.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Hasegawa, Kohei] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Hasegawa, Kohei] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hiraide, Atsushi] Kinki Univ, Fac Med, Dept Acute Med, Osaka, Japan. [Jha, Ashish K.] Harvard Global Hlth Inst, Cambridge, MA 02138 USA. [Jha, Ashish K.] Brigham & Womens Hosp, Dept Gen Internal Med, Boston, MA 02115 USA. [Jha, Ashish K.] Vet Affairs Boston Healthcare Syst, Boston, MA USA. RP Tsugawa, Y (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. EM tsugawa@fas.harvard.edu NR 25 TC 1 Z9 1 U1 1 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 2015 VL 5 IS 8 AR e008374 DI 10.1136/bmjopen-2015-008374 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CU4EH UT WOS:000363479100054 PM 26289451 ER PT J AU Villar, J Blanco, J del Campo, R Andaluz-Ojeda, D Diaz-Dominguez, FJ Muriel, A Corcoles, V Suarez-Sipmann, F Tarancon, C Gonzalez-Higueras, E Lopez, J Blanch, L Perez-Mendez, L Fernandez, RL Kacmarek, RM AF Villar, Jesus Blanco, Jesus del Campo, Rafael Andaluz-Ojeda, David Diaz-Dominguez, Francisco J. Muriel, Arturo Corcoles, Virgilio Suarez-Sipmann, Fernando Tarancon, Concepcion Gonzalez-Higueras, Elena Lopez, Julia Blanch, Lluis Perez-Mendez, Lina Fernandez, Rosa Lidia Kacmarek, Robert M. CA SIESTA Network TI Assessment of PaO2/FiO(2) for stratification of patients with moderate and severe acute respiratory distress syndrome SO BMJ OPEN LA English DT Article ID ACUTE LUNG INJURY; RANDOMIZED CONTROLLED-TRIAL; END-EXPIRATORY PRESSURE; HIGH-FREQUENCY OSCILLATION; BERLIN DEFINITION; TIDAL VOLUMES; MULTICENTER; VENTILATION; ARDS; OUTCOMES AB Objectives: A recent update of the definition of acute respiratory distress syndrome (ARDS) proposed an empirical classification based on ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO(2)) at ARDS onset. Since the proposal did not mandate PaO2/FiO(2) calculation under standardised ventilator settings (SVS), we hypothesised that a stratification based on baseline PaO2/FiO(2) would not provide accurate assessment of lung injury severity. Design: A prospective, multicentre, observational study. Setting: A network of teaching hospitals. Participants: 478 patients with eligible criteria for moderate (100300). Primary and secondary outcomes: Group severity and hospital mortality. Results: At ARDS onset, 173 patients had a PaO2/FiO(2)<= 100 but only 38.7% met criteria for severe ARDS at 24 h under SVS. When assessed under SVS, 61.3% of patients with severe ARDS were reclassified as moderate, mild and non-ARDS, while lung severity and hospital mortality changed markedly with every PaO2/FiO(2) category (p<0.000001). Our model of risk stratification outperformed the stratification using baseline PaO2/FiO(2) and non-standardised PaO2/FiO(2) at 24 h, when analysed by the predictive receiver operating characteristic (ROC) curve: area under the ROC curve for stratification at baseline was 0.583 (95% CI 0.525 to 0.636), 0.605 (95% CI 0.552 to 0.658) at 24 h without SVS and 0.693 (95% CI 0.645 to 0.742) at 24 h under SVS (p<0.000001). Conclusions: Our findings support the need for patient assessment under SVS at 24 h after ARDS onset to assess disease severity, and have implications for the diagnosis and management of ARDS patients. C1 [Villar, Jesus; Blanco, Jesus; Suarez-Sipmann, Fernando; Blanch, Lluis; Perez-Mendez, Lina; Fernandez, Rosa Lidia] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. [Villar, Jesus; Fernandez, Rosa Lidia] Hosp Univ Dr Negrin, Res Unit, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Las Palmas Gran Canaria, Spain. [Blanco, Jesus; Muriel, Arturo] Hosp Univ Rio Hortega, Intens Care Unit, Valladolid, Spain. [del Campo, Rafael] Hosp Gen Ciudad Real, Intens Care Unit, Ciudad Real, Spain. [Andaluz-Ojeda, David] Univ Valladolid, Hosp Clin, Intens Care Unit, Valladolid, Spain. [Diaz-Dominguez, Francisco J.] Hosp Univ Gen Leon, Intens Care Unit, Leon, Spain. [Corcoles, Virgilio] Complejo Hosp Univ Albacete, Intens Care Unit, Albacete, Spain. [Suarez-Sipmann, Fernando] Univ Uppsala Hosp, Hedenstierna Lab, Dept Surg Sci Anesthesiol & Crit Care, Uppsala, Sweden. [Tarancon, Concepcion] Hosp Virgen de la Concha, Intens Care Unit, Zamora, Spain. [Gonzalez-Higueras, Elena] Hosp Virgen de la Luz, Intens Care Unit, Cuenca, Spain. [Lopez, Julia] Hosp Univ La Paz, Intens Care Unit, Madrid, Spain. [Blanch, Lluis] Corp Sanitaria Parc Tauli, Crit Care Ctr, Sabadell, Spain. [Perez-Mendez, Lina] Hosp Univ NS Candelaria, Res Unit, Tenerife, Spain. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Kacmarek, Robert M.] Harvard Univ, Dept Anesthesiol, Boston, MA 02115 USA. RP Villar, J (reprint author), Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. EM jesus.villar54@gmail.com FU Instituto de Salud Carlos III, Madrid, Spain [PI 07/0113, PI10/0393, CB06/06/1088]; Asociacion Cientifica Pulmon y Ventilacion Mecanica, Las Palmas, Spain FX JV obtained grants from the Instituto de Salud Carlos III, Madrid, Spain (PI 07/0113, PI10/0393, CB06/06/1088) and Asociacion Cientifica Pulmon y Ventilacion Mecanica, Las Palmas, Spain. All researchers are independent of the funding bodies. NR 34 TC 16 Z9 16 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 2015 VL 5 IS 3 AR e006812 DI 10.1136/bmjopen-2014-006812 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CU3WZ UT WOS:000363458200056 PM 25818272 ER PT J AU Graff, JN Chamberlain, ED AF Graff, Julie N. Chamberlain, Erin D. TI Sipuleucel-T in the treatment of prostate cancer: an evidence-based review of its place in therapy SO CORE EVIDENCE LA English DT Review DE prostate cancer; sipuleucel-T; efficacy; economic analysis ID QUALITY-OF-LIFE; PHASE-III TRIAL; CELLULAR IMMUNOTHERAPY; INCREASED SURVIVAL; DOUBLE-BLIND; MITOXANTRONE; DOCETAXEL; CHEMOTHERAPY; PREDNISONE; ENZALUTAMIDE AB Metastatic castration-resistant prostate cancer is the lethal form of cancer of the prostate. Five new agents that prolong survival in this group have emerged in the past 5 years, and sipuleucel-T is among them. Sipuleucel-T is the only immunotherapy shown to improve survival in prostate cancer. It is currently indicated in asymptomatic or mildly symptomatic patients, as it has never shown a direct cancer effect. This paper describes the process of creating the sipuleucel-T product from the manufacturing and patient aspects. It discusses the four placebo-controlled, randomized clinical trials (RCTs) of sipuleucel-T, focusing on survival and adverse events. There are three RCTs in metastatic castration-resistant prostate cancer, all of which showed improved overall survival without meaningful decreases in symptoms, tumor volumes, or prostate-specific antigen levels. One RCT in castration-sensitive, biochemically relapsed prostate cancer attempted to find a decrease in biochemical failure, but that endpoint was not reached. Adverse events in all four of these studies centered around cytokine release. This paper also reviews a Phase II study of sipuleucel-T given neoadjuvantly that speaks to its mechanism of action. Additionally, there is a registry study of sipuleucel-T that has been used to evaluate immunological parameters of the product in men. 80 years of age and men who had previously been treated with palliative radiation. Attempts to find early markers of response to sipuleucel-T are described. Further ongoing studies that explore the efficacy of sipuleucel-T in combination with immune checkpoint inhibitors and second-generation hormonal therapies that are summarized. Finally, the only published economic analysis of sipuleucel-T is discussed. C1 [Graff, Julie N.] Portland VA Med Ctr, Portland, OR 97239 USA. [Graff, Julie N.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA. [Chamberlain, Erin D.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. RP Graff, JN (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd,MC P3CHEMO, Portland, OR 97239 USA. EM graffj@ohsu.edu NR 43 TC 7 Z9 7 U1 0 U2 12 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1555-1741 EI 1555-175X J9 CORE EVID JI Core Evid. PY 2015 VL 10 BP 1 EP 10 DI 10.2147/CE.S54712 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CU6RT UT WOS:000363661600001 PM 25565923 ER PT J AU Gross, R Zheng, L La Rosa, A Sun, X Rosenkranz, SL Cardoso, SW Ssali, F Camp, R Godfrey, C Cohn, SE Robbins, GK Chisada, A Wallis, CL Reynolds, NR Lu, D Safren, SA Hosey, L Severe, P Collier, AC AF Gross, Robert Zheng, Lu La Rosa, Alberto Sun, Xin Rosenkranz, Susan L. Cardoso, Sandra Wagner Ssali, Francis Camp, Rob Godfrey, Catherine Cohn, Susan E. Robbins, Gregory K. Chisada, Anthony Wallis, Carole L. Reynolds, Nancy R. Lu, Darlene Safren, Steven A. Hosey, Lara Severe, Patrice Collier, Ann C. CA ACTG 5234 Team TI Partner-based adherence intervention for second-line antiretroviral therapy (ACTG A5234): a multinational randomised trial SO LANCET HIV LA English DT Article ID SUB-SAHARAN AFRICA; CLINICAL-TRIALS; METAANALYSIS; FAILURE; RESISTANCE; OUTCOMES; USERS AB Background Adherence is key to the success of antiretroviral therapy. Enhanced partner support might benefit patients with previous treatment failure. We aimed to assess whether an enhanced partner-based support intervention with modified directly observed therapy would improve outcomes with second-line therapy in HIV-infected patients for whom first-line therapy had failed. Methods We did a multicentre, international, randomised clinical trial at nine sites in Botswana, Brazil, Haiti, Peru, South Africa, Uganda, Zambia, and Zimbabwe. Participants aged 18 years or older for whom first-line therapy had failed, with HIV RNA concentrations greater than 1000 copies per mL and with a willing partner, were randomly assigned (1: 1), via computer-generated randomisation, to receive partner-based modified directly observed therapy or standard of care. Randomisation was stratified by screening HIV RNA concentration (<= 10 000 copies per mL vs >10 000 copies per mL). Participants and site investigators were not masked to group assignment. Primary outcome was confirmed virological failure (viral load >400 copies per mL) by week 48. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00608569. Findings Between April 23, 2009, and Sept 29, 2011, we randomly assigned 259 participants to the modified directly observed therapy group (n=129) or the standard-of-care group (n=130). 34 (26%) participants in the modified directly observed therapy group achieved the primary endpoint of virological failure by week 48 compared with 23 (18%) participants in the standard-of-care group. The Kaplan-Meier estimated cumulative probability of virological failure by week 48 was 25.1% (95% CI 17.7-32.4) in the modified directly observed therapy group and 17.3% (10.8-23.7) in the standard-of-care group, for a weighted difference in standard of care versus modified directly observed therapy of -6.6% (95% CI -16.5% to 3.2%; p=0.19). 36 (14%) participants reported at least one grade 3 or higher adverse event or laboratory abnormality (n=21 in the modified directly observed therapy group and n=15 in the standard-of-care group). Interpretation Partner-based training with modified directly observed therapy had no effect on virological suppression. The intervention does not therefore seem to be a promising strategy to increase adherence. Intensive follow-up with clinic staff might be a viable approach in this setting. C1 [Gross, Robert] Univ Penn, Perelman Sch Med, Med Infect Dis & Epidemiol, Philadelphia, PA 19104 USA. [Zheng, Lu; Sun, Xin; Rosenkranz, Susan L.; Lu, Darlene] Harvard Univ, Sch Publ Hlth, Biostat, Boston, MA 02115 USA. [La Rosa, Alberto] Asociac Civil IMPACTA Salud & Educ, Lima, Peru. [Cardoso, Sandra Wagner] Fiocruz MS, BR-21045900 Rio De Janeiro, Brazil. [Ssali, Francis] Joint Clin Res Ctr, Kampala, Uganda. [Camp, Rob] EUPATI, Barcelona, Spain. [Godfrey, Catherine] NIAID, Bethesda, MD 20892 USA. [Cohn, Susan E.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Robbins, Gregory K.; Safren, Steven A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Robbins, Gregory K.; Safren, Steven A.] Harvard Univ, Sch Med, Boston, MA USA. [Chisada, Anthony] Univ Zimbabwe, Harare, Zimbabwe. [Wallis, Carole L.] Lancet Labs, Johannesburg, South Africa. [Reynolds, Nancy R.] Yale Univ, Sch Nursing, New Haven, CT 06536 USA. [Hosey, Lara] Social & Sci Syst, Silver Spring, MD USA. [Severe, Patrice] GHESKIO, Port Au Prince, Haiti. [Collier, Ann C.] Univ Washington, Seattle, WA 98195 USA. RP Gross, R (reprint author), Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. EM grossr@mail.med.upenn.edu FU National Institute of Allergy and Infectious Diseases [UM1AI068636, UM1AI069434, UM1AI069481, UM1AI068634, U01-AI069467]; National Institute of Mental Health, National Institute of Dental and Craniofacial Research; AIDS Clinical Trials Group Clinical Trials Unit [ACTG CTU] grant [AI 069421]; ACTG CTU grant [U01-A1069501, UM 1AI069436, AI069463, 2UM1AI069438-08, AI069438, 7UMIA1069455, 2UMIAI069456-08, AI069476] FX The project was supported by award numbers UM1AI068636, UM1AI069434, UM1AI069481, UM1AI068634, and U01-AI069467 from the National Institute of Allergy and Infectious Diseases and supported by National Institute of Mental Health, National Institute of Dental and Craniofacial Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. Abbott Laboratories and Gilead Pharmaceuticals provided the study drugs. We thank the study participants for their contributions and acknowledge the following individual sites' grant support, study team members, and site personnel: Valerie Francois and Samuel Pierre (Les Centres GHESKIO clinical research site 30022, AIDS Clinical Trials Group Clinical Trials Unit [ACTG CTU] grant AI 069421), Michael Ssemmanda and Haspha Nassolo (Joint Clinical Research Centre clinical research site 12401, ACTG CTU grant U01-A1069501), Wadzanai Samaneka and James G Hakim (Parirenyatwa clinical research site 30313, ACTG CTU grant UM 1AI069436), Mohammed Rassool and Pauline Vunandlala (Wits HIV clinical research site 11101, ACTG CTU grant AI069463), Jorge Sanchez and Fanny Rosas (Barranco clinical research site 11301, ACTG CTU grant 2UM1AI069438-08), Rosa Infante (San Miguel clinical research site 11302, ACTG CTU grant AI069438), Elizabeth Stringer and Margaret Kasaro (Kalingalinga Clinic clinical research site 12801, ACTG CTU grant 7UMIA1069455), Mpho Shakes Raesi and Lesedi Tirelo (Gaborone Prevention/Treatment Trials clinical research site 12701, ACTG CTU grant 2UMIAI069456-08 and Catalog of Federal Domestic Assistance grant 93.865), and Brenda Hoagland and Isabel Tavares (Instituto de Pesquisa Clinica Evandro Chagas clinical research site 12101, ACTG CTU grant AI069476). NR 28 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 2352-3018 J9 LANCET HIV JI Lancet HIV PD JAN PY 2015 VL 2 IS 1 BP E12 EP E19 DI 10.1016/S2352-3018(14)00007-1 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA CU8KP UT WOS:000363791600008 PM 25664336 ER PT J AU Lee, BH Lim, TH Yoon, YW Yenari, MA Jeong, Y AF Lee, Bae Hwan Lim, Tae-Hong Yoon, Young Wook Yenari, Midori A. Jeong, Yong TI Postinjury Neuroplasticity in Central Neural Networks SO NEURAL PLASTICITY LA English DT Editorial Material C1 [Lee, Bae Hwan] Yonsei Univ, Dept Physiol, Coll Med, Brain Korea PLUS Project Med Sci 21, Seoul 120752, South Korea. [Lim, Tae-Hong] Univ Iowa, Dept Biomed Engn, Coll Engn, Seamans Ctr Engn Arts & Sci, Iowa City, IA 52242 USA. [Yoon, Young Wook] Korea Univ, Dept Physiol, Coll Med, Seoul 136705, South Korea. [Yenari, Midori A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Yenari, Midori A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Jeong, Yong] Korea Adv Inst Sci & Technol, Dept Bio & Brain Engn, Daejeon 305701, South Korea. RP Lee, BH (reprint author), Yonsei Univ, Dept Physiol, Coll Med, Brain Korea PLUS Project Med Sci 21, Seoul 120752, South Korea. EM bhlee@yuhs.ac RI Jeong, Yong/C-1677-2011; OI Jeong, Yong/0000-0002-5907-3787; Lee, Bae H./0000-0003-4719-9021 NR 0 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 2090-5904 EI 1687-5443 J9 NEURAL PLAST JI Neural. Plast. PY 2015 AR 857085 DI 10.1155/2015/857085 PG 2 WC Neurosciences SC Neurosciences & Neurology GA CV3DP UT WOS:000364138900001 ER PT J AU Stein-Merlob, AF Kessinger, CW Erdem, SS Zelada, H Hilderbrand, SA Lin, CP Tearney, GJ Jaff, MR Reed, GL Henke, PK McCarthy, JR Jaffer, FA AF Stein-Merlob, Ashley F. Kessinger, Chase W. Erdem, S. Sibel Zelada, Henry Hilderbrand, Scott A. Lin, Charles P. Tearney, Guillermo J. Jaff, Michael R. Reed, Guy L. Henke, Peter K. McCarthy, Jason R. Jaffer, Farouc A. TI Blood Accessibility to Fibrin in Venous Thrombosis is Thrombus Age-Dependent and Predicts Fibrinolytic Efficacy: An In Vivo Fibrin Molecular Imaging Study SO THERANOSTICS LA English DT Article DE Fibrin; fibrinolysis; venous thrombosis; molecular imaging; pulmonary embolism ID DEEP-VEIN THROMBOSIS; NEAR-INFRARED FLUORESCENCE; PLASMINOGEN-ACTIVATOR; CONTRAST AGENT; PULMONARY-EMBOLISM; THROMBOLYSIS; RESOLUTION; INFLAMMATION; MECHANISMS; HEMORRHAGE AB Fibrinolytic therapy of venous thromboembolism (VTE) is increasingly utilized, yet limited knowledge is available regarding in vivo mechanisms that govern fibrinolytic efficacy. In particular, it is unknown how age-dependent thrombus organization limits direct blood contact with fibrin, the target of blood-based fibrinolytic agents. Utilizing high-resolution in vivo optical molecular imaging with FTP11, a near-infrared fluorescence (NIRF) fibrin-specific reporter, here we investigated the in vivo interrelationships of blood accessibility to fibrin, thrombus age, thrombus neoendothelialization, and fibrinolysis in murine venous thrombosis (VT). In both stasis VT and non-stasis VT, NIRF microscopy showed that FTP11 fibrin binding was thrombus age-dependent. FTP11 localized to the luminal surface of early-stage VT, but only minimally to subacute VT (p<0.001). Transmission electron microscopy of early stage VT revealed direct blood cell contact with luminal fibrin-rich surfaces. In contrast, subacute VT exhibited an encasing CD31+ neoendothelial layer that limited blood cell contact with thrombus fibrin in both VT models. Next we developed a theranostic strategy to predict fibrinolytic efficacy based on the in vivo fibrin accessibility to blood NIRF signal. Mice with variably aged VT underwent FTP11 injection and intravital microscopy (IVM), followed by tissue plasminogen activator infusion to induce VT fibrinolysis. Fibrin molecular IVM revealed that early stage VT, but not subacute VT, bound FTP11 (p<0.05), and experienced higher rates of fibrinolysis and total fibrinolysis (p<0.05 vs. subacute VT). Before fibrinolysis, the baseline FTP11 NIRF signal predicted the net fibrinolysis at 60 minutes (p<0.001). Taken together, these data provide novel insights into the temporal evolution of VT and its susceptibility to therapeutic fibrinolysis. Fibrin molecular imaging may provide a theranostic strategy to identify venous thrombi amenable to fibrinolytic therapies. C1 [Stein-Merlob, Ashley F.; Kessinger, Chase W.; Zelada, Henry; Jaff, Michael R.; Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr,Div Cardiol, Cambridge, MA 02138 USA. [Erdem, S. Sibel; Hilderbrand, Scott A.; Lin, Charles P.; McCarthy, Jason R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Cambridge, MA 02138 USA. [Lin, Charles P.; Tearney, Guillermo J.; Jaffer, Farouc A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Cambridge, MA 02138 USA. [Reed, Guy L.] Univ Tennessee, Hlth Sci Ctr, Dept Med, Knoxville, TN 37996 USA. [Henke, Peter K.] Univ Michigan, Dept Surg, Vasc Surg Sect, Ann Arbor, MI 48109 USA. RP Jaffer, FA (reprint author), 185 Cambridge St,Simches Res Bldg,Room 3206, Boston, MA 02114 USA. EM fjaffer@mgh.harvard.edu FU American Heart Association [12PRE11160000, 13POST14640021, 13GRNT17060040]; US National Institutes of Health [R01 HL108229, R01 HL122388-01A1, TPEN - HHSN268201000044C, R01 HL122238, T32 HL076136, R01 HL92750] FX The authors thank Margaret Sherwood and Megan Scanlan for assistance and expertise in TEM. This research was supported in part by the American Heart Association (#12PRE11160000, A.F.S.; #13POST14640021, T.H.; #13GRNT17060040, F.A.J.) and US National Institutes of Health (R01 HL108229 and R01 HL122388-01A1, F.A.J.; TPEN - HHSN268201000044C and R01 HL122238, J.R.M; T32 HL076136, C.W.K.; R01 HL92750, G.R.). NR 33 TC 0 Z9 0 U1 1 U2 1 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2015 VL 5 IS 12 BP 1317 EP 1327 DI 10.7150/thno.12494 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CU6XJ UT WOS:000363678100002 PM 26516370 ER PT B AU Kiernan, GD Yagoub, H Hynes, BG Kiernan, TJ Jaff, MR AF Kiernan, Gary D. Yagoub, Hatim Hynes, Brian G. Kiernan, Thomas J. Jaff, Michael R. BE Kipshidze, N Fareed, J Rosen, RJ Dangas, G Serruys, PW TI Principles of Diagnosis for, and Interventional Treatment of, Critical Leg Ischemia SO URGENT INTERVENTIONAL THERAPIES LA English DT Article; Book Chapter ID PERIPHERAL ARTERIAL-DISEASE; CRITICAL LIMB ISCHEMIA; ANKLE-BRACHIAL INDEX; PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY; DIGITAL-SUBTRACTION-ANGIOGRAPHY; OCCLUSIVE DISEASE; STENT IMPLANTATION; CARDIOVASCULAR EVENTS; METAL STENTS; FOLLOW-UP C1 [Kiernan, Gary D.] Mater Misericordiae Univ Hosp, Dept Cardiol, Dublin 7, Ireland. [Yagoub, Hatim] Natl Univ Ireland Univ Coll Cork, Sch Med, Cork Univ Hosp, Dept Cardiol, Cork, Ireland. [Hynes, Brian G.] Univ Coll Hosp Galway, Dept Cardiol, Galway, Ireland. [Kiernan, Thomas J.] Univ Limerick, Grad Entry Med Sch, Limerick Reg Hosp, Dept Cardiol, Limerick, Ireland. [Jaff, Michael R.] Massachusetts Gen Hosp, Vasc Ctr, Boston, MA 02114 USA. RP Kiernan, GD (reprint author), Mater Misericordiae Univ Hosp, Dept Cardiol, Dublin 7, Ireland. NR 36 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 978-1-118-50449-9; 978-0-470-67202-0 PY 2015 BP 313 EP 320 PG 8 WC Cardiac & Cardiovascular Systems; Emergency Medicine SC Cardiovascular System & Cardiology; Emergency Medicine GA BD5UR UT WOS:000361830000038 ER PT J AU Baheti, AD Shinagare, AB O'Neill, AC Krajewski, KM Hornick, JL George, S Ramaiya, NH Tirumani, SH AF Baheti, A. D. Shinagare, A. B. O'Neill, A. C. Krajewski, K. M. Hornick, J. L. George, S. Ramaiya, N. H. Tirumani, S. H. TI MDCT and clinicopathological features of small bowel gastrointestinal stromal tumours in 102 patients: a single institute experience SO BRITISH JOURNAL OF RADIOLOGY LA English DT Article ID IMAGING FEATURES; PATHOLOGICAL CORRELATION; SMALL-INTESTINE; RISK STRATIFICATION; CT FINDINGS; SPECTRUM; IMATINIB; RADIOLOGISTS; RECURRENCE; MUTATIONS AB Objective: Small bowel (SB) is the second most common site of gastrointestinal stromal tumours (GISTs). We evaluated clinical presentation, pathology, imaging features and metastatic pattern of SB GIST. Methods: Imaging and clinicopathological data of 102 patients with jejunal/ileal GIST treated at Dana-Farber Cancer Institute and Brigham and Women's Hospital (Boston, MA) between 2002 and 2013 were evaluated. Imaging of treatment-naive primary tumour (41 patients) and follow-up imaging in all patients was reviewed. Results: 90/102 patients were symptomatic at presentation, abdominal pain and lower gastrointestinal blood loss being the most common symptoms. On pathology, 21 GISTs were low risk, 17 were intermediate and 64 were high risk. The mean tumour size was 8.5 cm. On baseline CT (n=541), tumours were predominantly well circumscribed, exophytic and smooth/mildly lobulated in contour. Of 41 tumours, 16 (39%) were homogeneous, whereas 25 (61%) were heterogeneous. Of the 41 tumours, cystic/necrotic areas (Hounsfield units < 20) were seen in 16 (39%) and calcifications in 9 (22%). CT demonstrated complications in 13/41 (32%) patients in the form of tumour-bowel fistula (TBF) (7/41), bowel obstruction (4/41) and intraperitoneal rupture (2/41). Amongst 102 total patients, metastases developed in 51 (50%) patients (27 at presentation), predominantly involving peritoneum (40/102) and liver (32/102). 7/8 (87%) patients having intraperitoneal rupture at presentation developed metastases. Metastases elsewhere were always associated with hepatic/peritoneal metastases. At last follow-up, 28 patients were deceased (median survival, 65 months). Conclusion: SB GISTs were predominantly large, well-circumscribed, exophytic tumours with or without cystic/necrotic areas. Complications such as TBF, bowel obstruction and intraperitoneal perforation were visualized at presentation, with patients with perforation demonstrating a high risk of metastatic disease. Exophytic eccentric bowel wall involvement and lack of associated adenopathy are useful indicators to help differentiate GISTs from other SB neoplasms. Advances in knowledge: SB GISTs are predominantly large, well-circumscribed, exophytic tumours, and may present with complications. They often are symptomatic at presentation, are high risk on pathology and metastasize to the peritoneum more commonly than the liver. C1 [Baheti, A. D.; Shinagare, A. B.; O'Neill, A. C.; Krajewski, K. M.; Ramaiya, N. H.; Tirumani, S. H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Baheti, A. D.; Shinagare, A. B.; O'Neill, A. C.; Krajewski, K. M.; Ramaiya, N. H.; Tirumani, S. H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Hornick, J. L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [George, S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Baheti, AD (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. EM akshaybaheti@gmail.com NR 38 TC 2 Z9 3 U1 0 U2 3 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 EI 1748-880X J9 BRIT J RADIOL JI Br. J. Radiol. PY 2015 VL 88 IS 1053 AR 20150085 DI 10.1259/bjr.20150085 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CU1XD UT WOS:000363314700011 PM 26111069 ER PT J AU Tai, R Tirumani, SH Tirumani, H Shinagare, AB Hornick, JL Ramaiya, NH AF Tai, R. Tirumani, S. H. Tirumani, H. Shinagare, A. B. Hornick, J. L. Ramaiya, N. H. TI Is there a difference in post-transplant lymphoproliferative disorder in adults after solid organ and haematologic stem cell transplantation? Experience in 41 patients SO BRITISH JOURNAL OF RADIOLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; BONE-MARROW-TRANSPLANTATION; LIVER-TRANSPLANTATION; IMAGING FEATURES; DISTINCT ENTITY; DISEASE; ABDOMEN; RISK AB Objective: To determine if there is a difference in post-transplant lymphoproliferative disorder (PTLD) in adults after solid organ transplantation (SOT) and haematologic stem cell transplantation (HST). Methods: In this institutional review board-approved Health Insurance Portability and Accountability Act-compliant study, we reviewed clinical data and imaging at the time of diagnosis in 41 patients (26 SOT and 15 HST) (31 males and 10 females; mean age 51 years) with histopathology-confirmed PTLD seen at our institution from 2004 through 2013. Statistical analysis was performed to assess difference in distribution and survival between SOT and HST cohorts. Results: SOT: 17 lung/cardiac, 8 renal and 1 liver transplant recipients. HST: 13 leukaemia/lymphoma and 2 patients with aplastic anaemia. Median time to diagnosis: SOT 3.0 years; HST 6 months (Fisher's exact test; p=0.0011). There was no statistically significant difference in distribution of PTLD after SOT and HST with nodes (15/26; 8/15), lung (10/26; 5/15) and bowel (6/26; 4/15) being the most common sites. Hepatic (3/26) and neurologic (2/26) involvement occurred in only SOT cohort while splenic PTLD (5/15) occurred more often in HST cohort. Death occurred earlier in HST (9/15; 2 weeks) than SOT cohort (12/26; 11 months) (Wilcoxon test; p=0.0188). Conclusion: PTLD did not differ significantly in distribution between SOT and HST cohorts. PTLD after HST occurred early and had shorter survival. Advances in knowledge: The most common sites of PTLD were the nodes, lung and bowel. Distribution of PTLD does not differ significantly between patients with SOT and HST. PTLD after HST occurs early and has poor survival compared with PTLD after SOT. C1 [Tai, R.; Tirumani, S. H.; Shinagare, A. B.; Ramaiya, N. H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Tirumani, S. H.; Tirumani, H.; Shinagare, A. B.; Ramaiya, N. H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Hornick, J. L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Tirumani, SH (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. EM stirumani@partners.org NR 29 TC 1 Z9 1 U1 1 U2 1 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 EI 1748-880X J9 BRIT J RADIOL JI Br. J. Radiol. PY 2015 VL 88 IS 1052 AR 20140861 DI 10.1259/bjr.20140861 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CU1WN UT WOS:000363313000011 PM 25989696 ER PT J AU Schwarzer, R Rochau, U Saverno, K Jahn, B Bornschein, B Muehlberger, N Flatscher-Thoeni, M Schnell-Inderst, P Sroczynski, G Lackner, M Schall, I Hebborn, A Pugner, K Fehervary, A Brixner, D Siebert, U AF Schwarzer, Ruth Rochau, Ursula Saverno, Kim Jahn, Beate Bornschein, Bernhard Muehlberger, Nikolai Flatscher-Thoeni, Magdalena Schnell-Inderst, Petra Sroczynski, Gaby Lackner, Martina Schall, Imke Hebborn, Ansgar Pugner, Karl Fehervary, Andras Brixner, Diana Siebert, Uwe TI Systematic overview of cost-effectiveness thresholds in ten countries across four continents SO JOURNAL OF COMPARATIVE EFFECTIVENESS RESEARCH LA English DT Article DE cost-effectiveness thresholds; decision-making; health policy; reimbursement; technology assessment; willingness-to-pay ID ADJUSTED LIFE-YEAR; WILLINGNESS-TO-PAY; DRUG REIMBURSEMENT SYSTEMS; HEALTH ECONOMIC-ASSESSMENT; PERSONALIZED MEDICINE; DECISION-MAKING; CANCER; PHARMACOGENETICS; PERSPECTIVE; ONCOLOGY AB Aim: To provide an overview of thresholds for incremental cost-effectiveness ratios (ICERs) representing willingness-to-pay (WTP) across multiple countries and insights into exemptions pertaining to the ICER (e.g., cancer). To compare ICER thresholds to individual country's estimated ability-to-pay. Materials & methods: We included AHRQ/USA, BIQG-GOEG/Austria, CADTH/Canada, DAHTA@DIMDI/Germany, DECIT-CGATS/Brazil, HAS/France, HITAP/Thailand, IQWiG/Germany, LBI-HTA/Austria, MSAC/Australia, NICE/England/Wales and SBU/Sweden. ICER thresholds were derived from systematic literature/website search/expert surveys. WTP was compared with ATP using Spearman's rank correlation. Results: Two general and explicitly acknowledged thresholds (England/Wales, Thailand), implicit thresholds in six countries and different ICER thresholds/decision-making rules in oncology were identified. Correlation between WTP and ability-to-pay was moderate. Discussion: Our overview supports country-specific discussions on WTP and on how to define value(s) within societies. C1 [Schwarzer, Ruth; Rochau, Ursula; Saverno, Kim; Jahn, Beate; Bornschein, Bernhard; Muehlberger, Nikolai; Schnell-Inderst, Petra; Sroczynski, Gaby; Lackner, Martina; Schall, Imke; Brixner, Diana; Siebert, Uwe] UMIT Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth Hlth Serv Res & Hlth Technol Asses, Inst Publ Hlth Med Decis Making & Hlth Technol As, Eduard Wallnoefer Ctr 1, A-6060 Hall In Tirol, Austria. [Schwarzer, Ruth; Rochau, Ursula; Jahn, Beate; Schnell-Inderst, Petra; Sroczynski, Gaby; Brixner, Diana; Siebert, Uwe] ONCOTYROL Ctr Personalized Canc Med, Div Publ Hlth Decis Modelling Hlth Technol Assess, A-6020 Innsbruck, Austria. [Saverno, Kim; Brixner, Diana] Univ Utah, Dept Pharmacotherapy, Salt Lake City, UT 84112 USA. [Flatscher-Thoeni, Magdalena] UMIT Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth & Hlth Technol Assessment, Program Hlth Policy Adm Econ & Law, A-6060 Hall In Tirol, Austria. [Hebborn, Ansgar] F Hoffmann La Roche & Cie AG, Market Access Policy, CH-4070 Basel, Switzerland. [Pugner, Karl] Amgen Inc, Dept Hlth Econ & Reimbursement, CH-6301 Zug, Switzerland. [Fehervary, Andras] Novartis Int AG, Govt Affairs Europe, CH-4002 Basel, Switzerland. [Brixner, Diana] Univ Utah, Dept Pharmacotherapy, Outcomes Res Ctr, Program Personalized Hlth Care, Salt Lake City, UT 84112 USA. [Brixner, Diana] Harvard Univ, Dept Hlth Policy & Management, Ctr Hlth Decis Sci, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Siebert, Uwe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Siebert, Uwe] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Siebert, U (reprint author), UMIT Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth Hlth Serv Res & Hlth Technol Asses, Inst Publ Hlth Med Decis Making & Hlth Technol As, Eduard Wallnoefer Ctr 1, A-6060 Hall In Tirol, Austria. EM public-health@umit.at FU COMET Center ONCOTYROL; Austrian Federal Ministries BMVIT/BMWFJ (via FFG); Tiroler Zukunftsstiftung/Standortagentur Tirol (SAT) FX This work was supported by the COMET Center ONCOTYROL, which is funded by the Austrian Federal Ministries BMVIT/BMWFJ (via FFG) and the Tiroler Zukunftsstiftung/Standortagentur Tirol (SAT). K Pugner is an employee of Amgen, Zug, Switzerland; A Hebborn is an employee of F Hoffmann-La Roche AG, Basel, Switzerland; A Fehervary was an employee of Novartis, Basel, Switzerland. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 94 TC 2 Z9 2 U1 1 U2 7 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 2042-6305 EI 2042-6313 J9 J COMP EFFECT RES JI J. Comp. Eff. Res. PY 2015 VL 4 IS 5 BP 485 EP 504 DI 10.2217/cer.15.38 PG 20 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CU3BE UT WOS:000363397600007 PM 26490020 ER PT J AU Simon, C Kudahl, UJ Sun, J Olsen, LR Zhang, GL Reinherz, EL Brusic, V AF Simon, Christian Kudahl, Ulrich J. Sun, Jing Olsen, Lars Ronn Zhang, Guang Lan Reinherz, Ellis L. Brusic, Vladimir TI FluKB: A Knowledge-Based System for Influenza Vaccine Target Discovery and Analysis of the Immunological Properties of Influenza Viruses SO JOURNAL OF IMMUNOLOGY RESEARCH LA English DT Article ID MULTIPLE SEQUENCE ALIGNMENT; PROTEIN DATA-BANK; VISUALIZATION; IMMUNITY; DATABASE AB FluKB is a knowledge-based system focusing on data and analytical tools for influenza vaccine discovery. The main goal of FluKB is to provide access to curated influenza sequence and epitope data and enhance the analysis of influenza sequence diversity and the analysis of targets of immune responses. FluKB consists of more than 400,000 influenza protein sequences, known epitope data (357 verified T-cell epitopes, 685 HLA binders, and 16 naturally processed MHC ligands), and a collection of 28 influenza antibodies and their structurally defined B-cell epitopes. FluKB was built using a modular framework allowing the implementation of analytical workflows and includes standard search tools, such as keyword search and sequence similarity queries, as well as advanced tools for the analysis of sequence variability. The advanced analytical tools for vaccine discovery include visual mapping of T- and B-cell vaccine targets and assessment of neutralizing antibody coverage. FluKB supports the discovery of vaccine targets and the analysis of viral diversity and its implications for vaccine discovery as well as potential T-cell breadth and antibody cross neutralization involving multiple strains. FluKB is representation of a new generation of databases that integrates data, analytical tools, and analytical workflows that enable comprehensive analysis and automatic generation of analysis reports. C1 [Simon, Christian; Kudahl, Ulrich J.] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Simon, Christian] Univ Copenhagen, Dept Dis Syst Biol, Novo Nordisk Fdn Ctr Prot Res, DK-2200 Copenhagen, Denmark. [Kudahl, Ulrich J.; Sun, Jing; Olsen, Lars Ronn; Zhang, Guang Lan; Reinherz, Ellis L.; Brusic, Vladimir] Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Olsen, Lars Ronn] Univ Copenhagen, Dept Biol, Bioinformat Ctr, DK-1017 Copenhagen, Denmark. [Zhang, Guang Lan; Brusic, Vladimir] Boston Univ, Dept Comp Sci, Metropolitan Coll, Boston, MA 02215 USA. [Zhang, Guang Lan; Reinherz, Ellis L.; Brusic, Vladimir] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Reinherz, Ellis L.] Dana Farber Canc Inst, Immunobiol Lab, Dept Med Oncol, Boston, MA 02115 USA. RP Brusic, V (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Canc Vaccine Ctr, 44 Binney St, Boston, MA 02115 USA. EM vladimir.brusic@nu.edu.kz OI Simon, Christian/0000-0002-5866-5967 FU NIH [U01 AI90043] FX This work was supported by the NIH Grant U01 AI90043. NR 39 TC 2 Z9 2 U1 0 U2 1 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 2314-8861 EI 2314-7156 J9 J IMMUNOL RES JI J Immunol. Res. PY 2015 AR 380975 DI 10.1155/2015/380975 PG 11 WC Immunology SC Immunology GA CU0AF UT WOS:000363177000001 ER PT S AU Wiggs, JL AF Wiggs, Janey L. BE Hejtmancik, JF Nickerson, JM TI Glaucoma Genes and Mechanisms SO MOLECULAR BIOLOGY OF EYE DISEASE SE Progress in Molecular Biology and Translational Science LA English DT Review; Book Chapter ID OPEN-ANGLE GLAUCOMA; GENOME-WIDE ASSOCIATION; PRIMARY CONGENITAL GLAUCOMA; UNFOLDED PROTEIN RESPONSE; AXENFELD-RIEGER-SYNDROME; NORMAL-TENSION GLAUCOMA; BETA-BINDING PROTEIN-2; TRABECULAR MESHWORK; INTRAOCULAR-PRESSURE; COMMON VARIANTS AB Genetic studies have yielded important genes contributing to both early-onset and adult-onset forms of glaucoma. The proteins encoded by the current collection of glaucoma genes participate in a broad range of cellular processes and biological systems. Approximately half the glaucoma-related genes function in the extracellular matrix, however proteins involved in cytokine signaling, lipid metabolism, membrane biology, regulation of cell division, autophagy, and ocular development also contribute to the disease pathogenesis. While the function of these proteins in health and disease are not completely understood, recent studies are providing insight into underlying disease mechanisms, a critical step toward the development of gene-based therapies. In this review, genes known to cause early-onset glaucoma or contribute to adult-onset glaucoma are organized according to the cell processes or biological systems that are impacted by the function of the disease-related protein product. C1 [Wiggs, Janey L.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Wiggs, Janey L.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Wiggs, JL (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM Janey_Wiggs@meei.harvard.edu FU NEI NIH HHS [P30 EY014104] NR 169 TC 5 Z9 5 U1 0 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1877-1173 BN 978-0-12-801267-3; 978-0-12-801059-4 J9 PROG MOL BIOL TRANSL JI Prog. Molec. Biol. Transl. Sci. PY 2015 VL 134 BP 315 EP 342 DI 10.1016/bs.pmbts.2015.04.008 PG 28 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA BD7MP UT WOS:000363312000020 PM 26310163 ER PT J AU Framme, C Walter, A Berger, L Prahs, P Alt, C Theisen-Kunde, D Kowal, J Brinkmann, R AF Framme, Carsten Walter, Andreas Berger, Lieselotte Prahs, Philipp Alt, Clemens Theisen-Kunde, Dirk Kowal, Jens Brinkmann, Ralf TI Selective Retina Therapy in Acute and Chronic-Recurrent Central Serous Chorioretinopathy SO OPHTHALMOLOGICA LA English DT Article DE Central serous chorioretinopathy; Chronic disease; Acute disease; Selective retina treatment; Subretinal fluid; Fluorescein angiography ID OPTICAL COHERENCE TOMOGRAPHY; RPE LASER TREATMENT; TERM-FOLLOW-UP; PIGMENT EPITHELIUM; MINERALOCORTICOID RECEPTOR; PHOTODYNAMIC THERAPY; MACULAR DISEASES; TREATMENT SRT; TIME REGIMEN; PHOTOCOAGULATION AB Purpose: Selective retina therapy (SRT), the confined laser heating and destruction of retinal pigment epithelial cells, has been shown to treat acute types of central serous chorioretinopathy (CSC) successfully without damaging the photoreceptors and thus avoiding laser-induced scotoma. However, a benefit of laser treatment for chronic forms of CSC is questionable. In this study, the efficacy of SRT by means of the previously used 1.7-mu s and shorter 300-ns pulse duration was evaluated for both types of CSC, also considering re-treatment for nonresponders. Material and Methods: In a two-center trial, 26 patients were treated with SRT for acute (n = 10) and chronic-recurrent CSC (n = 16). All patients presented with subretinal fluid (SRF) in OCT and leakage in fluorescein angiography (FA). SRT was performed using a prototype SRT laser system (frequency-doubled Q-switched Nd:YLF-laser, wavelength 527 nm) with adjustable pulse duration. The following irradiation settings were used: a train of 30 laser pulses with a repetition rate of 100 Hz and pulse durations of 300 ns and 1.7 mu s, pulse energy 120-200 mu J, retinal spot size 200 mu m. Because SRT lesions are invisible, FA was always performed 1 h after treatment to demonstrate laser outcome (5-8 single spots in the area of leakage). In cases where energy was too low, as indicated by missing FA leakage, energy was adjusted and the patient re-treated immediately. Observation intervals were after 4 weeks and 3 months. In case of nonimprovement of the disease after 3 months, re-treatment was considered. Results: Of 10 patients with active CSC that presents focal leakage in FA, 5 had completely resolved fluid after 4 weeks and all 10 after 3 months. Mean visual acuity increased from 76.6 ETDRS letters to 85.0 ETDRS letters 3 months after SRT. Chronic-recurrent CSC was characterized by less severe SRF at baseline in OCT and weaker leakage in FA than in acute types. Visual acuity changed from baseline 71.6 to 72.8 ETDRS letters after 3 months. At this time, SRF was absent in 3 out of 16 patients (19%), FA leakage had come to a complete stop in 6 out of 16 patients (38%). In 6 of the remaining chronic CSC patients, repeated SRT with higher pulse energy was considered because of persistent leakage activity. After the re-treatment, SRF resolved completely in 5 patients (83.3%) after only 25 days. Conclusion: SRT showed promising results in treating acute CSC, but was less effective in chronic cases. Interestingly, re-treatment resulted in enhanced fluid resolution and dry conditions after a considerably shorter time in most patients. Therefore, SRT including re-treatment if necessary might be a valuable CSC treatment alternative even in chronic-recurrent cases. (C) 2015 S. Karger AG, Basel C1 [Framme, Carsten] Univ Eye Hosp, Hannover Med Sch, DE-30625 Hannover, Germany. [Walter, Andreas] Eye Hosp Dresden Friedrichstadt, Dresden, Germany. [Prahs, Philipp] Univ Eye Hosp Regensburg, Regensburg, Germany. [Theisen-Kunde, Dirk; Brinkmann, Ralf] Med Laser Ctr Lubeck GmbH, Lubeck, Germany. [Berger, Lieselotte; Kowal, Jens] Univ Eye Hosp Bern, Bern, Switzerland. [Alt, Clemens] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Welman Labs Photomed, Boston, MA USA. RP Framme, C (reprint author), Univ Eye Hosp, Hannover Med Sch, Carl Neuberg Str 1, DE-30625 Hannover, Germany. EM Framme.Carsten@mh-hannover.de RI Brinkmann, Ralf/E-6701-2012 FU Jackstaedt foundation in Wuppertal, Germany FX The authors would like to thank the Jackstaedt foundation in Wuppertal, Germany, for the generous financial support of the SRT study in both University Eye Hospitals Regensburg, Germany, and Inselspital Bern, Switzerland. NR 42 TC 1 Z9 1 U1 0 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-3755 EI 1423-0267 J9 OPHTHALMOLOGICA JI Ophthalmologica PY 2015 VL 234 IS 4 BP 177 EP 188 DI 10.1159/000439188 PG 12 WC Ophthalmology SC Ophthalmology GA CU3NW UT WOS:000363433100001 PM 26368551 ER PT J AU Tuzova, M Conniff, T Curiel-Lewandrowski, C Chaney, K Cruikshank, W Wolpowitz, D AF Tuzova, Marina Conniff, Tara Curiel-Lewandrowski, Clara Chaney, Keri Cruikshank, William Wolpowitz, Deon TI Absence of Full-length Neurokinin-1 Receptor Protein Expression by Cutaneous T Cells: Implications for Substance P-mediated Signaling in Mycosis Fungoides SO ACTA DERMATO-VENEREOLOGICA LA English DT Editorial Material ID PRURITUS; LYMPHOCYTE; SEVERITY C1 [Tuzova, Marina; Cruikshank, William] Boston Univ, Sch Med, Pulm Ctr, Boston, MA 02118 USA. [Conniff, Tara; Wolpowitz, Deon] Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. [Conniff, Tara; Wolpowitz, Deon] Boston Univ, Sch Med, Sect Dermatopathol, Boston, MA 02118 USA. [Curiel-Lewandrowski, Clara] Arizona State Univ, Arizona Canc Ctr, Tucson, AZ USA. [Chaney, Keri] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wolpowitz, D (reprint author), Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. EM dewolpow@bu.edu FU CTSA NIH [UL1-TR000157]; NIH [R01CA122737-01A2] FX The authors thank Natalie Adams and Lynne Morrison, who consented MF patients and collected blood samples at DFCI and AZCC; Oksana Hradyska and Phillip Vartanyan for technical assistance; and Dr. Michael Kirber, Boston University Cellular Imaging Core, for imaging assistance. This study was supported in part by CTSA NIH grant UL1-TR000157 and by NIH R01CA122737-01A2. NR 13 TC 0 Z9 0 U1 1 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 2015 VL 95 IS 7 BP 852 EP 854 DI 10.2340/00015555-2097 PG 3 WC Dermatology SC Dermatology GA CT6LW UT WOS:000362925500019 PM 25783846 ER PT J AU Foraker, J Millard, SP Leong, L Thomson, Z Chen, S Keene, CD Bekris, LM Yu, CE AF Foraker, Jessica Millard, Steven P. Leong, Lesley Thomson, Zachary Chen, Sunny Keene, C. Dirk Bekris, Lynn M. Yu, Chang-En TI The APOE Gene is Differentially Methylated in Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; apolipoprotein E; CGI; CpG island; DMR; DNA methylation; epigenetics; pyrosequencing ID DNA METHYLATION; HUMAN BRAIN; GENOME; HYDROXYMETHYLATION; ALLELE; CELLS; ANK1; AGE AB The epsilon 4 allele of the human apolipoprotein E gene (APOE) is a well-proven genetic risk factor for the late onset form of Alzheimer's disease (AD). However, the biological mechanisms through which the epsilon 4 allele contributes to disease pathophysiology are incompletely understood. The three common alleles of APOE, epsilon 2, epsilon 3 and epsilon 4, are defined by two single nucleotide polymorphisms (SNPs) that reside in the coding region of exon 4, which overlaps with a well-defined CpG island (CGI). Both SNPs change not only the protein codon but also the quantity of CpG dinucleotides, primary sites for DNA methylation. Thus, we hypothesize that the presence of an epsilon 4 allele changes the DNA methylation landscape of the APOE CGI and that such epigenetic alteration contributes to AD susceptibility. To explore the relationship between APOE genotype, AD risk, and DNA methylation of the APOE CGI, we applied bisulfite pyrosequencing and evaluated methylation profiles of postmortem brain from 15 AD and 10 control subjects. We observed a tissue-specific decrease in DNA methylation with AD and identified two AD-specific differentially methylated regions (DMRs), which were also associated with APOE genotype. We further demonstrated that one DMR was completely un-methylated in a sub-population of genomes, possibly due to a subset of brain cells carrying deviated APOE methylation profiles. These data suggest that the APOE CGI is differentially methylated in AD brain in a tissue-and APOE-genotype-specific manner. Such epigenetic alteration might contribute to neural cell dysfunction in AD brain. C1 [Foraker, Jessica; Leong, Lesley; Thomson, Zachary; Chen, Sunny; Yu, Chang-En] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Millard, Steven P.] VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Foraker, Jessica; Yu, Chang-En] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA. [Keene, C. Dirk] Univ Washington, Dept Pathol, Neuropathol Div, Seattle, WA 98195 USA. [Bekris, Lynn M.] Cleveland Clin Fdn, Lerner Res Inst, Genom Med Inst, Cleveland, OH 44195 USA. RP Foraker, J (reprint author), VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, 1660S Columbian Way,Box 358280, Seattle, WA 98108 USA. EM jforaker@u.washington.edu RI Keene, Christopher/N-1806-2015 FU U.S. Department of Veterans Affairs Office of Research and Development Biomedical Laboratory Research Program; National Institute of Health/National Institute on Aging grants [P50 AG05136, T32 AG000258] FX This work was supported in part by the U.S. Department of Veterans Affairs Office of Research and Development Biomedical Laboratory Research Program and National Institute of Health/National Institute on Aging grants (P50 AG05136 and T32 AG000258). NR 33 TC 3 Z9 3 U1 3 U2 14 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2015 VL 48 IS 3 BP 745 EP 755 DI 10.3233/JAD-143060 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CT6YE UT WOS:000362958800017 PM 26402071 ER PT B AU Sperandio, FF Sabino, CP Vecchio, D Garcia-Diaz, M Huang, LY Huang, YY Hamblin, MR AF Sperandio, Felipe F. Sabino, Caetano P. Vecchio, Daniela Garcia-Diaz, Maria Huang, Liyi Huang, Ying-Ying Hamblin, Michael R. BE DeFreitas, PM Simoes, A TI Antimicrobial photodynamic therapy in dentistry SO LASERS IN DENTISTRY: GUIDE FOR CLINICAL PRACTICE LA English DT Article; Book Chapter ID RECURRENT HERPES LABIALIS; EXPERIMENTAL PERIODONTAL-DISEASE; ROOT SUBSTANCE REMOVAL; IN-VITRO; ENTEROCOCCUS-FAECALIS; NEUTRAL-RED; LETHAL PHOTOSENSITIZATION; IMMUNOSUPPRESSED RATS; SIMPLEX LABIALIS; PERI-IMPLANTITIS C1 [Sperandio, Felipe F.] Univ Fed Alfenas, Inst Biomed Sci, Dept Pathol & Parasitol, Alfenas, MG, Brazil. [Sperandio, Felipe F.; Vecchio, Daniela; Huang, Liyi; Huang, Ying-Ying; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Sperandio, Felipe F.; Sabino, Caetano P.; Vecchio, Daniela; Garcia-Diaz, Maria; Huang, Liyi; Huang, Ying-Ying; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Sabino, Caetano P.] IPEN CNEN SP, Ctr Lasers & Applicat, Sao Paulo, SP, Brazil. [Garcia-Diaz, Maria] Univ Ramon Llull, IQS Sch Engn, Mol Engn Grp, Barcelona, Spain. [Huang, Liyi] Guangxi Med Univ, Affiliated Coll & Hosp 1, Dept Infect Dis, Nanning, 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 Sperandio, FF (reprint author), Univ Fed Alfenas, Inst Biomed Sci, Dept Pathol & Parasitol, Alfenas, MG, Brazil. RI Garcia-Diaz, Maria/J-9202-2014 OI Garcia-Diaz, Maria/0000-0002-4794-5437 NR 84 TC 1 Z9 1 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA BN 978-1-118-27502-3; 978-1-118-98774-2 PY 2015 BP 40 EP 47 D2 10.1002/9781118987742 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BD5FE UT WOS:000361378900009 ER PT B AU Sperandio, FF Huang, YY Parizotto, N Hamblin, MR AF Sperandio, Felipe F. Huang, Ying-Ying Parizotto, Nivaldo Hamblin, Michael R. BE DeFreitas, PM Simoes, A TI Nerve repair by light SO LASERS IN DENTISTRY: GUIDE FOR CLINICAL PRACTICE LA English DT Article; Book Chapter ID LOW-LEVEL LASER; INFERIOR ALVEOLAR NERVE; TRAUMATIC BRAIN-INJURY; RAT SCIATIC-NERVE; LOW-ENERGY LASER; PERIPHERAL-NERVE; TRIGEMINAL NEURALGIA; BELLS-PALSY; DOUBLE-BLIND; SPINAL-CORD C1 [Sperandio, Felipe F.] Univ Fed Alfenas, Inst Biomed Sci, Dept Pathol & Parasitol, Alfenas, MG, Brazil. [Sperandio, Felipe F.; Huang, Ying-Ying; Parizotto, Nivaldo; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Sperandio, Felipe F.; Huang, Ying-Ying; Parizotto, Nivaldo; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Huang, Ying-Ying] Guangxi Med Univ, Aesthet & Plast Ctr, Nanning, Peoples R China. [Parizotto, Nivaldo] Univ Fed Sao Carlos, Dept Physiotherapy, BR-13560 Sao Carlos, SP, Brazil. [Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. RP Sperandio, FF (reprint author), Univ Fed Alfenas, Inst Biomed Sci, Dept Pathol & Parasitol, Alfenas, MG, Brazil. NR 73 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA BN 978-1-118-27502-3; 978-1-118-98774-2 PY 2015 BP 293 EP 301 D2 10.1002/9781118987742 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA BD5FE UT WOS:000361378900040 ER PT B AU Guo, NN Gatchel, J Sahay, A AF Guo, Nannan Gatchel, Jennifer Sahay, Amar BE Kuhn, HG Eisch, AJ TI The Role of Adult-Born Dentate Granule Neurons in the Regulation of Mood SO NEURAL STEM CELLS IN DEVELOPMENT, ADULTHOOD AND DISEASE SE Stem Cell Biology and Regenerative Medicine LA English DT Article; Book Chapter ID STEM-CELL FATE; HIPPOCAMPAL NEUROGENESIS; PATTERN SEPARATION; SYNAPTIC PLASTICITY; VENTRAL SUBICULUM; ANTIDEPRESSANT ACTIONS; NEUROTROPHIC FACTOR; DEPRESSED-PATIENTS; CRITICAL PERIOD; NMDA RECEPTORS C1 [Guo, Nannan; Gatchel, Jennifer; Sahay, Amar] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Guo, Nannan; Gatchel, Jennifer; Sahay, Amar] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Sahay, Amar] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res,Psychiat & Neurodev Genet Uni, Boston, MA 02114 USA. [Sahay, Amar] Harvard Univ, Harvard Stem Cell Inst, Boston, MA 02114 USA. RP Sahay, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St,CPZN Room 4242, Boston, MA 02114 USA. EM asahay@mgh.harvard.edu NR 69 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4939-1908-6; 978-1-4939-1907-9 J9 STEM CELLS BIOL REG JI Stem Cell Biol. Regen. Med. PY 2015 BP 41 EP 52 DI 10.1007/978-1-4939-1908-6_3 D2 10.1007/978-1-4939-1908-6 PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA BD7CT UT WOS:000362894900004 ER PT B AU Hoyt, K AF Hoyt, Kendall BE Rushton, S Youde, J TI MEDICAL COUNTERMEASURES AND SECURITY SO ROUTLEDGE HANDBOOK OF GLOBAL HEALTH SECURITY LA English DT Article; Book Chapter ID INNOVATION C1 [Hoyt, Kendall] Dartmouth Coll, Geisel Sch Med, Hanover, NH 03755 USA. [Hoyt, Kendall] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Hoyt, Kendall] Natl Acad Sci Comm, Dept Def Programs Counter Biol Threats, Washington, DC USA. [Hoyt, Kendall] Massachusetts Gen Hosp, Advisory Board, Vaccine & Immunotherapy Ctr, Boston, MA 02114 USA. RP Hoyt, K (reprint author), Dartmouth Coll, Geisel Sch Med, Hanover, NH 03755 USA. NR 31 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE PI ABINGDON PA 2 PARK SQ, MILTON PARK, ABINGDON OX14 4RN, OXFORD, ENGLAND BN 978-0-203-07856-3; 978-0-415-64547-8 PY 2015 BP 215 EP 225 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BD5BB UT WOS:000361310300019 ER PT J AU Bicket, MC Chakravarthy, K Chang, D Cohen, SP AF Bicket, Mark C. Chakravarthy, Krishnan Chang, David Cohen, Steven P. TI Epidural steroid injections: an updated review on recent trends in safety and complications SO PAIN MANAGEMENT LA English DT Review DE adverse event; caudal; complication; epidural steroid injection; laminar; review; safety; spinal injection; transforaminal ID LOW-BACK-PAIN; CERVICAL TRANSFORAMINAL INJECTION; BONE-MINERAL DENSITY; LUMBAR RADICULAR PAIN; CENTRAL SEROUS CHORIORETINOPATHY; DIGITAL-SUBTRACTION-ANGIOGRAPHY; BLOOD-GLUCOSE LEVELS; SPINAL-CORD-INJURY; OF-THE-LITERATURE; NECK PAIN AB Epidural steroid injections (ESIs), which can provide significant but temporary pain relief in well-selected patients, are the most commonly performed procedure in pain management. The anatomy of the epidural space provides a framework for understanding risks associated with ESIs, a topic relevant to both patients and physicians in interventional pain, surgery and primary care. Safety considerations of epidural steroids include drug preparation and myriad physiological effects stemming from steroid exposure. Although major complications associated with ESI occur rarely, potentially catastrophic events resulting from infectious, hematologic and neurologic morbidity may lead to permanent injury. The safety profile of ESIs may improve with development and dissemination of sound injection technique, safer compounds manufactured in a sterile manner and deficient of thromboembolic potential and the application of existing technology. C1 [Bicket, Mark C.] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA. [Chakravarthy, Krishnan; Chang, David; Cohen, Steven P.] Johns Hopkins Pain Treatment Ctr, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA. [Cohen, Steven P.] Johns Hopkins Sch Med, Dept Phys Med & Rehabil, Baltimore, MD 21205 USA. RP Cohen, SP (reprint author), Johns Hopkins Pain Treatment Ctr, Dept Anesthesiol & Crit Care Med, 550 North Broadway,Suite 301, Baltimore, MD 21205 USA. EM scohen40@jhmi.edu NR 146 TC 6 Z9 6 U1 0 U2 3 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1758-1869 EI 1758-1877 J9 PAIN MANAG JI Pain Manag. PY 2015 VL 5 IS 2 BP 129 EP 146 DI 10.2217/PMT.14.53 PG 18 WC Clinical Neurology SC Neurosciences & Neurology GA CT2XM UT WOS:000362669100010 PM 25806907 ER PT J AU Emani, S Ting, DY Healey, M Lipsitz, SR Ramelson, H Suric, V Bates, DW AF Emani, S. Ting, D. Y. Healey, M. Lipsitz, S. R. Ramelson, H. Suric, V. Bates, D. W. TI Physician Perceptions and Beliefs about Generating and Providing a Clinical Summary of the Office Visit SO APPLIED CLINICAL INFORMATICS LA English DT Article DE Electronic health records; meaningful use; after visit summary; physicians; beliefs; evaluation ID ELECTRONIC HEALTH RECORDS; MEANINGFUL USE; INFORMATION-TECHNOLOGY; ADOPTION AB Background: A core measure of the meaningful use of EHR incentive program is the generation and provision of the clinical summary of the office visit, or the after visit summary (AVS), to patients. However, little research has been conducted on physician perceptions and beliefs about the AVS. Objective: Evaluate physician perceptions and beliefs about the AVS and the effect of the AVS on workload, patient outcomes, and the care the physician delivers. Methods: A cross-sectional online survey of physicians at two academic medical centers (AMCs) in the northeast who are participating in the meaningful use EHR incentive program. Results: Of the 1 795 physicians at both AMCs participating in the incentive program, 853 completed the survey for a response rate of 47.5%. Eighty percent of the respondents reported that the AVS was easy (very easy or quite easy or somewhat easy) to generate and provide to patients. Nonetheless, more than three-fourths of the respondents reported a negative effect of generating and providing the AVS on workload of office staff (78%) and workload of physicians (76%). Primary care physicians had more positive beliefs about the effect of the AVS on patient outcomes than specialists (p< 0.001) and also had more positive beliefs about the effect of the AVS on the care they delivered than specialists (p< 0.001). Conclusions: Achieving the core meaningful use measure of generating and providing the AVS was easy for physicians but it did not necessarily translate into positive beliefs about the effect of the AVS on patient outcomes or the care the physician delivered. Physicians also had negative beliefs about the effect of the AVS on workload. To promote positive beliefs among physicians around the AVS, organizations should obtain physician input into the design and implementation of the AVS and develop strategies to mitigate its negative impacts on workload. C1 [Emani, S.; Healey, M.; Lipsitz, S. R.; Suric, V.; Bates, D. W.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Gen Internal Med,Dept Med, Boston, MA 02115 USA. [Ting, D. Y.] Massachusetts Gen Hosp, Massachusetts Gen Phys Org, Boston, MA 02114 USA. [Healey, M.] Brigham & Womens Hosp, Brigham & Womens Phys Org, Boston, MA 02120 USA. [Ramelson, H.] Partners HealthCare, Informat Serv, Boston, MA USA. [Bates, D. W.] Harvard Univ, Sch Publ Hlth, Dept Healthcare Policy & Management, Boston, MA 02115 USA. RP Emani, S (reprint author), Brigham & Womens Hosp, Div Gen Internal Med, 1620 Tremont St,3rd Floor, Boston, MA 02120 USA. EM semani1@partners.org FU Partners Siemens Research Council FX Funding for this study was provided by the Partners Siemens Research Council. NR 19 TC 1 Z9 1 U1 1 U2 1 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 1869-0327 J9 APPL CLIN INFORM JI Appl. Clin. Inform. PY 2015 VL 6 IS 3 BP 577 EP 590 DI 10.4338/ACI-2015-04-RA-0043 PG 14 WC Medical Informatics SC Medical Informatics GA CS7KU UT WOS:000362263300012 PM 26448799 ER PT J AU Chi, YF Chai, JK Yu, YM Luo, HM Zhang, QX Feng, R AF Chi, Y. F. Chai, J. K. Yu, Y. M. Luo, H. M. Zhang, Q. X. Feng, R. TI Association between PAI-1 polymorphisms and plasma PAI-1 level with sepsis in severely burned patients SO GENETICS AND MOLECULAR RESEARCH LA English DT Article DE Burn; Plasminogen activator inhibitor-1; Polymorphism; Sepsis ID 4G/5G PROMOTER POLYMORPHISM; UNITED-STATES; EPIDEMIOLOGY; DEFINITIONS AB We investigated the association between plasminogen activator inhibitor-1 (PAI-1) polymorphisms and plasma PAI-1 level with sepsis in severely burned patients. A total of 182 patients with burn areas lager than 30% of the body surface area were enrolled in this study. Peripheral blood samples were obtained from 103 patients with sepsis (sepsis group) and 79 patients without sepsis (control group). An allele-specific polymerase chain reaction assay was used to determine PAI-1 polymorphism 4G/5G distribution. Plasma PAI-1 levels were detected using an enzyme-linked immunosorbent assay. The frequency of the 4G/4G genotype and the 4G allele frequency in the sepsis group were 42.7 and 62.1% respectively, which were significantly higher than those in the control group (P < 0.05). Sepsis patients had a significantly higher plasma PAI-1 level than the control group (P < 0.05). Compared with the 5G/5G genotype, PAI-1 concentrations were significantly higher in the 4G/4G genotype (P < 0.05). The study indicates that the 4G/5G promoter polymorphism of PAI-1 gene may be related to the susceptibility to burn sepsis and that the 4G/4G genotype may be an important genetic risk factor of burn sepsis. Additionally, PAI-1 concentrations in the serum are increased in patients with burn sepsis. C1 [Chi, Y. F.; Chai, J. K.; Luo, H. M.; Zhang, Q. X.; Feng, R.] Peoples Liberat Army Gen Hosp, Hosp 1, Dept Burn & Plast Surg, Beijing, Peoples R China. [Yu, Y. M.] Shriners Hosp Children, Boston, MA USA. [Yu, Y. M.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Chi, YF (reprint author), Peoples Liberat Army Gen Hosp, Hosp 1, Dept Burn & Plast Surg, Beijing, Peoples R China. EM chiyunfei_cyf@163.com NR 12 TC 0 Z9 0 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 2015 VL 14 IS 3 BP 10081 EP 10086 DI 10.4238/2015.August.21.15 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA CS9OV UT WOS:000362421500155 PM 26345945 ER PT J AU Raab, PA Mackintosh, MA Gros, DF Morland, LA AF Raab, Phillip A. Mackintosh, Margaret-Anne Gros, Daniel F. Morland, Leslie A. TI Impact of comorbid depression on quality of life in male combat Veterans with posttraumatic stress disorder SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE comorbidity; depression; major depressive disorder; MDD; negative affect; numbing; posttraumatic stress disorder; PTSD; quality of life; Veterans ID COGNITIVE PROCESSING THERAPY; ADMINISTERED PTSD SCALE; ANXIETY DISORDERS; MAJOR DEPRESSION; GULF-WAR; SYMPTOMS; HEALTH; IMPAIRMENT; MILITARY; EXPOSURE AB For Veterans with posttraumatic stress disorder (PTSD), depression is a highly comorbid condition. Both conditions have been associated with decreased quality of life, and research suggests that comorbid PTSD and depression may result in worse quality of life than PTSD alone. However, research is needed to elucidate the effect of comorbidity on a broader variety of quality of life domains. In this study, we used baseline data of 158 male combat Veterans taking part in a PTSD treatment trial and examined the unique relationships between quality of life domains and PTSD symptom clusters, major depressive disorder (MDD) diagnosis, and self-reported depressive symptoms. Veterans with comorbid PTSD-MDD reported significantly worse satisfaction-related quality of life than those with PTSD alone, although this finding was largely attributable to PTSD numbing symptoms. Subsequent analyses comparing the effect of numbing symptoms to depressive symptoms revealed that depression exerted a stronger influence, although numbing symptoms were still uniquely associated with quality of life. We discuss implications for treatment and research, as well as the need to address negative affect in Veterans with PTSD. C1 [Raab, Phillip A.; Mackintosh, Margaret-Anne; Morland, Leslie A.] Dept Vet Affairs VA Pacific Isl Hlth Care Syst, Natl Ctr Posttraumat Stress Disorder, Pacific Isl Div, Honolulu, HI USA. [Gros, Daniel F.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Gros, Daniel F.] Med Univ S Carolina, Charleston, SC 29425 USA. [Morland, Leslie A.] Univ Hawaii Manoa, John A Burns Sch Med, Honolulu, HI 96822 USA. RP Raab, PA (reprint author), Natl Ctr Posttraumat Stress Disorder, Pacific Isl Div, 3375 Koapaka St,Suite I-560, Honolulu, HI 96819 USA. EM drewraab@gmail.com FU VA Office of Research and Development, Health Services Research & Development Service [DHI 07-259]; Department of Defense, Congressionally Directed Medical Research Programs [PT074516]; VA National Center for PTSD FX This material was based on work supported in part by the VA Office of Research and Development, Health Services Research & Development Service (grant DHI 07-259) and the Department of Defense, Congressionally Directed Medical Research Programs (grant PT074516). Support was also provided by the VA National Center for PTSD and with resources and the use of facilities at Spark M. Matsunaga Medical Center, VA Pacific Islands Health Care System. NR 52 TC 3 Z9 3 U1 0 U2 0 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 EI 1938-1352 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PY 2015 VL 52 IS 5 BP 563 EP 576 DI 10.1682/JRRD.2014.05.0130 PG 14 WC Rehabilitation SC Rehabilitation GA CT2HQ UT WOS:000362623000006 PM 26466310 ER PT J AU Dean, JC Kautz, SA AF Dean, Jesse C. Kautz, Steven A. TI Foot placement control and gait instability among people with stroke SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE balance; biomechanics; foot placement; frontal plane; kinematics; motor control; muscle activity; stability; stroke; walking ID BERG BALANCE SCALE; OLDER-ADULTS; LATERAL PERTURBATIONS; DYNAMIC STABILITY; HEALTHY-ADULTS; FALL INCIDENCE; WALKING; COMMUNITY; POSTSTROKE; PREVENTION AB Gait instability is a common problem following stroke, as evidenced by increases in fall risk and fear of falling. However, the mechanism underlying gait instability is currently unclear. We recently found that young, healthy humans use a consistent gait stabilization strategy of actively controlling their mediolateral foot placement based on the concurrent mechanical state of the stance limb. In the present work, we tested whether people with stroke (n = 16) and age-matched controls (n = 19) used this neuromechanical strategy. Specifically, we used multiple linear regressions to test whether (1) swing phase gluteus medius (GM) activity was influenced by the simultaneous state of the stance limb and (2) mediolateral foot placement location was influenced by swing phase GM activity and the mechanical state of the swing limb at the start of the step. We found that both age-matched controls and people with stroke classified as having a low fall risk (Dynamic Gait Index [DGI] score >19) essentially used the stabilization strategy previously described in young controls. In contrast, this strategy was disrupted for people with stroke classified as higher fall risk (DGI 139mmHg or diastolic>89mmHg) was 14.6% for wood users compared to 19.6% for gas users although this did not reach significance after adjustment, using propensity score techniques, for factors that make wood and gas users distinct (adjusted prevalence ratio 0.76; 95% CI: 0.49, 1.17). Conclusions: Combustion products from the burning of biomass fuels are similar to those released with tobacco smoking, which has been linked with a reduced risk for preeclampsia. The direction of our findings suggests the possibility of a similar effect for biomass cook smoke. Whether clean cooking interventions being promoted by international advocacy organizations will impact hypertension in pregnancy warrants further analysis as hypertension remains a leading cause of maternal death worldwide and cooking with biomass fuels is widespread. C1 [Wylie, Blair J.] Harvard Univ, Massachusetts Gen Hosp, Div Maternal Fetal Med, Vincent Dept Obstet & Gynecol,Med Sch, Boston, MA USA. [Wylie, Blair J.; Coull, Brent A.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Singh, Mrigendra P.; Singh, Neeru] Indian Council Med Res, RMRCT, Natl Inst Malaria Res Field Stn, Jabalpur, Madhya Pradesh, India. [Coull, Brent A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Quinn, Ashlinn] Columbia Univ, Dept Environm Hlth Sci, Mailman Sch Publ Hlth, New York, NY USA. [Yeboah-Antwi, Kojo; Sabin, Lora; Hamer, Davidson H.; MacLeod, William B.] Boston Univ, Ctr Global Hlth & Dev, Boston, MA 02215 USA. [Yeboah-Antwi, Kojo; Sabin, Lora; Hamer, Davidson H.; MacLeod, William B.] Boston Univ, Sch Publ Hlth, Dept Global Hlth, Boston, MA USA. [Hamer, Davidson H.] Boston Univ, Sch Med, Dept Med, Infect Dis Sect, Boston, MA 02118 USA. [Hamer, Davidson H.] Zambia Ctr Appl Hlth Res & Dev, Lusaka, Zambia. [Singh, Neeru] Indian Council Med Res, Reg Med Res Ctr Tribals, Jabalpur, Madhya Pradesh, India. RP Wylie, BJ (reprint author), Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Div Maternal Fetal Med, Founders 4,55 Fruit St, Boston, MA 02114 USA. EM bwylie@mgh.harvard.edu FU United States Agency for International Development (USAID)/India [GHS-A-00-03-00020-00]; Indo-U.S. Collaborative Network; Indian Council for Medical Research (ICMR); National Institute of Child Health and Development [1 R03 HD52167-01]; National Institute of Environmental Health Sciences [NIH K23 ES021471]; National Institutes of Health [NIH ES 000002] FX The United States Agency for International Development (USAID)/India mission provided funding for this study to the Child and Family Applied Research project at Boston University, Boston, MA, by means of the USAID cooperative agreement (GHS-A-00-03-00020-00). This work was also supported by the Indo-U.S. Collaborative Network with funding from the Indian Council for Medical Research (ICMR) and the National Institute of Child Health and Development (1 R03 HD52167-01). BJW was supported by the National Institute of Environmental Health Sciences (NIH K23 ES021471). B.A.C. was supported by the National Institutes of Health (NIH ES 000002). NR 47 TC 1 Z9 1 U1 2 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1064-1955 EI 1525-6065 J9 HYPERTENS PREGNANCY JI Hypertens. Pregnancy PY 2015 VL 34 IS 3 BP 355 EP 368 DI 10.3109/10641955.2015.1046604 PG 14 WC Obstetrics & Gynecology; Physiology; Peripheral Vascular Disease SC Obstetrics & Gynecology; Physiology; Cardiovascular System & Cardiology GA CR4RP UT WOS:000361325600008 PM 26153626 ER PT J AU Hundemer, GL Sise, ME Wisocky, J Ufere, N Friedman, LS Corey, KE Chung, RT AF Hundemer, Gregory L. Sise, Meghan E. Wisocky, Jessica Ufere, Nneka Friedman, Lawrence S. Corey, Kathleen E. Chung, Raymond T. TI Use of sofosbuvir-based direct-acting antiviral therapy for hepatitis C viral infection in patients with severe renal insufficiency SO INFECTIOUS DISEASES LA English DT Article DE Hepatitis C; sofosbuvir; chronic kidney disease; end-stage renal disease ID HEMODIALYSIS-PATIENTS; VIRUS; RIBAVIRIN; EFFICACY; IMPACT AB Sofosbuvir-based direct-acting antiviral therapy revolutionized the treatment of hepatitis C virus (HCV) infection. However, sofosbuvir use is not approved for patients with severe renal insufficiency (estimated glomerular filtration (eGFR) rate below 30 ml/min) or end-stage renal disease (ESRD) based on concerns raised during premarket animal testing over hepatobiliary and cardiovascular toxicity in this population. We report the first published data on use of sofosbuvir-based regimens in patients with severe renal insufficiency and ESRD, focusing on clinical efficacy and safety. Six patients were treated with full dose sofosbuvir; three received sofosbuvir and simeprevir, two received sofosbuvir and ribavirin, and one received sofosbuvir, ribavirin, and interferon. Three of the patients had cirrhosis. On-treatment viral suppression was 100% and sustained virological response (SVR) rate at 12 weeks was 67%. One patient had to discontinue antiviral therapy early due to side effects. No hepatobiliary or cardiovascular toxicity was reported. C1 [Hundemer, Gregory L.; Ufere, Nneka] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Sise, Meghan E.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Wisocky, Jessica; Corey, Kathleen E.; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Friedman, Lawrence S.] Newton Wellesley Hosp, Dept Med, Newton, MA USA. [Hundemer, Gregory L.; Sise, Meghan E.; Wisocky, Jessica; Ufere, Nneka; Friedman, Lawrence S.; Corey, Kathleen E.; Chung, Raymond T.] Harvard Univ, Sch Med, Boston, MA USA. [Friedman, Lawrence S.] Tufts Univ, Sch Med, Boston, MA 02111 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Ctr Liver, GI Div, Warren 1007,55 Fruit St, Boston, MA 02114 USA. EM msise@mgh.harvard.edu; rtchung@partners.org FU NIH [K24 DK078772]; Gilead Sciences; Bristol Myers Squibb; Abbvie Pharmaceuticals; Janssen; Merck; ASN Foundation FX Funding received: NIH K24 DK078772 (RTC), ASN Foundation for Kidney Research Fellows Award (M.E.S.). M.E.S. discloses receiving research grant from Gilead Sciences. L.S.F. discloses royalties from Elsevier, UpToDate, McGraw-Hill, and Wiley. K.E.C. discloses prior history on advisory boards for Gilead Sciences. R.T.C. discloses research grants from Gilead Sciences, Bristol Myers Squibb, Abbvie Pharmaceuticals, Janssen, and Merck. NR 16 TC 17 Z9 17 U1 1 U2 9 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 2374-4235 EI 2374-4243 J9 INFECT DIS-NOR JI Infect. Dis. PY 2015 VL 47 IS 12 BP 924 EP 929 DI 10.3109/23744235.2015.1078908 PG 6 WC Infectious Diseases SC Infectious Diseases GA CR4VH UT WOS:000361337300014 PM 26365684 ER PT J AU Zhang, FY Hang, JQ Zheng, BY Su, L Christiani, DC AF Zhang, Fengying Hang, Jingqing Zheng, Buyong Su, Li Christiani, David C. TI The changing epidemiology of asthma in Shanghai, China SO JOURNAL OF ASTHMA LA English DT Article DE Asthma; China; epidemiology ID QUALITY-OF-LIFE; PREVALENCE; MANAGEMENT; SYMPTOMS; BURDEN; HEALTH AB Objective: To investigate the prevalence of bronchial asthma in Putuo district in Shanghai, China. Methods: Cross-sectional, community-based study was performed with random sampling of a district with a population of one million. The subjects were residents of the district and six or more years of age. Questionnaire and spirometry were completed in all subjects. Asthma was defined as physician-diagnosed asthma. The results were compared with the asthma study of 40 000 population completed by the same team in Pudong area of Shanghai in 1997. Results: We surveyed 27 042 participants. The prevalence of asthma was 1.8% (488/27 042), much higher than the 0.41% (163/40 000) found in the 1997 survey in Pudong area of Shanghai. In subjects with asthma, current smoking, obesity, gender distribution and the combination of allergic diseases between the two studies had no differences. The most prominent causes of asthma exacerbation were cold air, respiratory infection and dust inhalation. Pulmonary function for 428 asthma patients in Putuo survey was analyzed: 228 (53.3%) patients had FEV1% pred lower than 80%. Asthmatics older than 65 years had lower FEV1% pred than other age groups (p50.01). Conclusions: The prevalence of physician-diagnosed asthma in urban of Shanghai has increased in recent years. The most important causes of asthma exacerbations were cold air, respiratory infection and dust exposure. The proportion of individuals with decreased percent predicted forced expiratory volume of first second increased with age. Strengthening the prevention and treatment of asthma, especially in children with asthma, may decrease the health burden of asthma in the urban Chinese population. C1 [Zhang, Fengying; Hang, Jingqing; Zheng, Buyong] Shanghai Putuo Dist Peoples Hosp, Dept Resp Med, Shanghai, Peoples R China. [Su, Li; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA. [Christiani, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Christiani, David C.] Harvard Univ, Sch Med, Boston, MA USA. RP Hang, JQ (reprint author), Shanghai Putuo Dist Peoples Hosp, Dept Resp Med, Shanghai, Peoples R China. EM hangjq@hotmail.com FU Shanghai Municipal Health Bureau [05II015]; National Institute of Environmental Health Science of the United States [ES000002] FX This study was funded by the Shanghai Municipal Health Bureau [grant 05II015], the National Institute of Environmental Health Science of the United States [grant ES000002]. NR 30 TC 1 Z9 1 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0277-0903 EI 1532-4303 J9 J ASTHMA JI J. Asthma PY 2015 VL 52 IS 5 BP 465 EP 470 DI 10.3109/02770903.2014.982762 PG 6 WC Allergy; Respiratory System SC Allergy; Respiratory System GA CR4VZ UT WOS:000361339100005 PM 25387151 ER PT J AU Plenter, RJ Jain, S Nydam, TL Jani, AH AF Plenter, Robert J. Jain, Swati Nydam, Trevor L. Jani, Alkesh H. TI Revised Arterial Anastomosis for Improving Murine Kidney Transplant Outcomes SO JOURNAL OF INVESTIGATIVE SURGERY LA English DT Article DE mouse; renal; graft ID HETEROTOPIC CARDIAC TRANSPLANTATION; RENAL-TRANSPLANTATION; MICE; MOUSE; THROMBOSIS; SURVIVAL; VESSELS; INTACT; RAT AB Aim: One of the most challenging research microsurgical techniques is the mouse kidney transplant however, very few laboratories have made use of this important model due to its difficulty. One of the main obstacles to utilizing this procedure is the high incidence of post-operative arterial thrombosis. We believe this is caused by the path in which blood is required to flow from the recipient abdominal aorta, via the donor recipient aorta and on into the renal artery creating a tortuous route and areas of turbulence, which are prone to thrombus formation and failure of the graft. Methods: We describe revised methods of donor artery recovery, whereby the traditional transection of the donor aorta is replaced with a heel and toe cuff, which is created by dividing the donor abdominal aorta obliquely across the face of the renal arterial ostium, which then provides for an arterial end-to-side anastomosis of a scale similar to that used for the heterotopic heart model. This technique produces an anastomosis that facilitates free blood flow from the recipient abdominal aorta at less than 90 degrees thereby reducing the likelihood of thrombus formation. Results: Utilizing this new technique the incidence of arterial thrombosis has decreased from 35% to 0% (n = 20 and 24, respectively) with no change in ischemia times. Conclusion: We describe a revised method of performing the arterial anastomosis during mouse kidney transplantation, which facilitates improved fluid dynamics by straightening the flow path for blood to the graft resulting in significantly reduced thrombus formation, excellent graft function, histology, and post-transplant survival. C1 [Plenter, Robert J.] Univ Colorado Denver, Div Pulm Sci & Crit Care Med, Dept Med, Aurora, CO 80045 USA. [Plenter, Robert J.; Nydam, Trevor L.] Univ Colorado Denver, Colorado Ctr Transplantat Care Res & Educ, Dept Surg, Aurora, CO 80045 USA. [Jain, Swati; Jani, Alkesh H.] Denver VA Med Ctr, Div Renal Dis & Hypertens, Dept Med, Aurora, CO USA. [Jain, Swati; Jani, Alkesh H.] Univ Colorado Denver, Aurora, CO 80045 USA. [Nydam, Trevor L.] Univ Colorado Denver, Univ Colorado Sch Med, Dept Surg, Div Transplant Surg, Aurora, CO 80045 USA. RP Plenter, RJ (reprint author), Univ Colorado Denver, Colorado Ctr Transplantat Care Res & Educ, 1775 Aurora Ct,Box B-140, Aurora, CO 80045 USA. EM robert.plenter@ucdenver.edu FU NIH [1R03-DK-096151-01] FX This study was supported by NIH grant 1R03-DK-096151-01 (A.H.J.). NR 21 TC 2 Z9 2 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0894-1939 EI 1521-0553 J9 J INVEST SURG JI J. Invest. Surg. PY 2015 VL 28 IS 4 BP 208 EP 214 DI 10.3109/08941939.2014.1002641 PG 7 WC Surgery SC Surgery GA CR4TB UT WOS:000361330500005 PM 26087146 ER PT J AU Polymeri, AA Kodovazenitis, GJ Polymeris, AD Komboli, M AF Polymeri, Angeliki A. Kodovazenitis, George J. Polymeris, Antonios D. Komboli, Mado TI Bisphosphonates: Clinical Applications and Adverse Events in Dentistry SO ORAL HEALTH & PREVENTIVE DENTISTRY LA English DT Review DE bisphosphonates; bone density; jaw osteonecrosis; osteoporosis; periodontal disease ID SURGEONS POSITION PAPER; ALVEOLAR BONE; RISK-FACTORS; INDUCED OSTEONECROSIS; ORAL BISPHOSPHONATES; PERIODONTAL-DISEASE; TOOTH EXTRACTION; POSTMENOPAUSAL OSTEOPOROSIS; INTRAVENOUS BISPHOSPHONATES; AMERICAN ASSOCIATION AB Purpose: To review the mechanisms of action and clinical applications of bisphosphonate drugs, which are widely used in the management of metastatic bone cancer and systemic metabolic bone diseases, as well as the complications related to bisphosphonate treatment, emphasising the occurrence and management of bisphosphonate-related osteonecrosis of the jaws (BRONJ). Materials and Methods: A search of the medical and dental literature was conducted in Medline and Embase using a combination of the key words bisphosphonates, jaw, complications, osteonecrosis, osteoporosis and periodontal disease. A manual search of the references of the retrieved articles was also performed. Results: BRONJ predominantly affects cancer patients being treated with high-dose intravenous bisphosphonates and is characterised by the appearance of necrotic bone in the oral cavity either spontaneously or following an invasive surgical procedure such as dental extraction. The severity of this condition warrants a thorough medical and dental history in every patient in order to identify high risk patients. Conclusion: It is important that dental practitioners be aware of the association between bisphosphonate treatment and osteonecrosis of the jaws. Clinicians should perform a thorough oral examination in cancer patients before they begin intravenous bisphosphonate treatment. Optimal oral hygiene and regular dental care can lower BRONJ risk. Further clinical research is necessary to unveil the full therapeutic potential of bisphosphonates, their mechanisms of action and the factors that induce unwanted side-effects. C1 [Polymeri, Angeliki A.] Forsyth Inst, Appl Mol Photomed Lab, Cambridge, MA 02142 USA. [Polymeris, Antonios D.] Alexandra Gen Hosp, Dept Endocrinol 2, Athens, Greece. [Komboli, Mado] Univ Athens, Dept Periodontol, Athens, Greece. RP Polymeri, AA (reprint author), Forsyth Inst, Appl Mol Photomed Lab, 245 First St, Cambridge, MA 02142 USA. EM polyan.dent@gmail.com NR 78 TC 1 Z9 1 U1 1 U2 7 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA SN 1602-1622 EI 1757-9996 J9 ORAL HLTH PREV DENT JI Oral Health Prev. Dent. PY 2015 VL 13 IS 4 BP 289 EP 299 DI 10.3290/j.ohpd.a34370 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CR5ZM UT WOS:000361422900002 PM 26106647 ER PT J AU Lewis, RF AF Lewis, Richard F. TI Vestibular Prostheses Investigated in Animal Models SO ORL-JOURNAL FOR OTO-RHINO-LARYNGOLOGY HEAD AND NECK SURGERY LA English DT Review DE Vestibular function; Vertigo; Prosthesis; Implant; Ataxia ID SEMICIRCULAR CANAL AFFERENTS; ELECTRICAL-STIMULATION; RHESUS-MONKEYS; ADAPTATION; PSYCHOPHYSICS AB Loss of peripheral vestibular function results in debilitating postural, perceptual, and visual symptoms. A new approach to treating this clinical problem is to replace some aspects of peripheral vestibular function with a prosthesis that senses head motion and provides this information to the brain by stimulating the vestibular nerve. In this paper, I review studies done in animals over the past 15 years which lay the groundwork for transferring this approach to human patients with severe peripheral vestibular damage. The animal studies demonstrate that the visual and perceptual defects associated with peripheral vestibular damage can be improved with a vestibular implant, but the data on postural control remain less conclusive at this point in time. (C) 2015 S. Karger AG, Basel C1 [Lewis, Richard F.] Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. [Lewis, Richard F.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Lewis, Richard F.] Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. RP Lewis, RF (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol,Vestibular Physiol Lab, 243 Charles St, Boston, MA 02114 USA. EM Richard_lewis@meei.harvard.edu FU National Institutes of Health; MED-EL Corporation FX This work has been funded by the National Institutes of Health and by MED-EL Corporation. NR 22 TC 2 Z9 2 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-1569 EI 1423-0275 J9 ORL J OTO-RHINO-LARY JI ORL-J. Oto-Rhino-Laryngol. Head Neck Surg. PY 2015 VL 77 IS 4 BP 219 EP 226 DI 10.1159/000433551 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA CR5YI UT WOS:000361419900003 PM 26366706 ER PT S AU Ablon, SL AF Ablon, Steven Luria BE Abrams, S King, RA Brinich, PM Lament, C Knight, R TI What Child Analysis Can Teach Us about Psychoanalytic Technique SO PSYCHOANALYTIC STUDY OF THE CHILD, VOL 68 SE Psychoanalytic Study of the Child LA English DT Article; Book Chapter AB Child analysis has much to teach us about analytic technique. Children have an innate, developmentally driven sense of analytic process. Children in analysis underscore the importance of an understanding and belief in the therapeutic action of play, the provisional aspects of play, and that not all play will be understood. Each analysis requires learning a new play signature that is constantly reorganized. Child analysis emphasizes the emergence and integration of dissociated states, the negotiation of self-other relationships, the importance of co-creation, and the child's awareness of the analyst's sensibility. Child analysis highlights the robust nature of transference and how working through and repairing is related to the initiation of coordinated patterns of high predictability in the context of deep attachments. I will illustrate these and other ideas in the description of the analysis of a nine-year-old boy. C1 [Ablon, Steven Luria] Boston Psychoanalyt Soc & Inst, Newton Ctr, MA 02459 USA. [Ablon, Steven Luria] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. RP Ablon, SL (reprint author), Boston Psychoanalyt Soc & Inst, Newton Ctr, MA 02459 USA. NR 38 TC 0 Z9 0 U1 0 U2 0 PU YALE UNIV PRESS PI NEW HAVEN PA 302 TEMPLE ST, NEW HAVEN, CT 06511 USA SN 0079-7308 BN 978-0-300-20741-5 J9 PSYCHOANAL STUD CHIL JI Psychoanal. Stud. Child PY 2015 VL 68 BP 211 EP 224 PG 14 WC Psychology, Psychoanalysis SC Psychology GA BD5GC UT WOS:000361399900013 ER PT J AU Colussi, D Salari, B Stewart, KO Lauwers, GY Richter, JR Chan, AT Ricciardiello, L Khalili, H AF Colussi, Dora Salari, Behzad Stewart, Kathleen O. Lauwers, Gregory Y. Richter, James R. Chan, Andrew T. Ricciardiello, Luigi Khalili, Hamed TI Clinical characteristics and patterns and predictors of response to therapy in collagenous and lymphocytic colitis SO SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY LA English DT Article DE bismuth subsalicylate; budesonide; cholestyramine; collagenous colitis; loperamide; lymphocytic colitis; microscopic colitis; treatment patterns and response ID PLACEBO-CONTROLLED TRIAL; MICROSCOPIC COLITIS; DOUBLE-BLIND; BUDESONIDE TREATMENT; ORAL BUDESONIDE; FOLLOW-UP; REMISSION; DISEASE AB Background. Collagenous colitis (CC) and lymphocytic colitis (LC) are chronic inflammatory disorders of the colon. There is a paucity of data on differences in etiology, natural history, and treatment response between CC and LC. Methods. Between 2002 and 2013, we identified new diagnoses of CC and LC using the Research Patient Data Registry in a tertiary referral center. We used chi square or Fischer's exact test and Wilcoxon rank-sum tests to compare the differences in clinical characteristics, treatment types, and response rates between LC and CC. Results: Through 2013, we confirmed 131 patients with a new diagnosis of microscopic colitis (MC) (55 LC, 76 CC). Compared to cases of LC, patients with a diagnosis of CC were more likely to be women (86% vs. 69%, p = 0.03), have elevated erythrocyte sedimentation rate (mean 28 vs. 13 mm/h, p = 0.04), and less likely to be diabetic (5% vs. 18%, p = 0.02). Budesonide was the most effective treatment for both CC and LC (94% and 80%, respectively). However, there were no statistically significant differences in response to various treatments according to the type of MC (all p > 0.10). Older age at the time of diagnosis was associated with better response to bismuth subsalicylate (odds ratio: 1.76; 95% confidence interval: 1.21-2.56 for every 5-year increase) for both CC and LC. Conclusion. Despite differences in the clinical characteristics, response rates to available treatments appeared to be similar in both LC and CC. Older patients may have a better response to bismuth subsalicylate therapy. C1 [Colussi, Dora; Salari, Behzad; Stewart, Kathleen O.; Richter, James R.; Chan, Andrew T.; Khalili, Hamed] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Colussi, Dora; Salari, Behzad; Stewart, Kathleen O.; Lauwers, Gregory Y.; Richter, James R.; Chan, Andrew T.; Khalili, Hamed] Harvard Univ, Sch Med, Boston, MA USA. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Chan, Andrew T.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Ricciardiello, Luigi] Univ Bologna, Dept Med & Surg Sci, Gastroenterol Unit, Bologna, Italy. RP Khalili, H (reprint author), Massachusetts Gen Hosp, Digest Healthcare Ctr, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM hkhalili@mgh.harvard.edu OI RICCIARDIELLO, LUIGI/0000-0003-2568-6208 FU Crohn's and Colitis Foundation of America (CCFA); American Gastroenterological Association (AGA); National Institute of Diabetes and Digestive and Kidney Diseases [K23 DK099681]; Italian Association for Cancer Research (AIRC) [14281]; European Community [311876]; [R01 CA137178]; [R01 CA050385]; [P01 CA87969]; [CA49449]; [CA67262]; [P30 DK043351]; [K24 098311]; [K23 DK091742] FX Grant Support: Funded by R01 CA137178, R01 CA050385, P01 CA87969, CA49449, CA67262, P30 DK043351, K24 098311, and K23 DK091742. Dr. Chan is supported by a senior investigator grant from the Crohn's and Colitis Foundation of America (CCFA). Dr. Khalili is supported by a career development award from the American Gastroenterological Association (AGA) and by National Institute of Diabetes and Digestive and Kidney Diseases (K23 DK099681). Dr. Ricciardiello is supported by the Italian Association for Cancer Research (AIRC - Investigator Grant n. 14281) and by the European Community's Seventh Framework Program (Pathway-27) under grant agreement n. 311876. Ethical Approval: The institutional review board at the Partners Healthcare approved this study. Data sharing: Requests for access to data, statistical code, questionnaires, and technical processes may be made by contacting the corresponding author at hkhalili@mgh.harvard.edu. Authors Contributions: Hamed Khalili takes responsibility for the integrity of the work as a whole, from inception to published article. BS - acquisition of data; drafting of the manuscript. KS - acquisition of data; critical revision of the manuscript. GYL - study concept and design; critical revision of the manuscript for important intellectual content. JMR - study concept and design; critical revision of the manuscript. ATC - study concept and design; critical revision of the manuscript. LR - study concept and design; critical revision of the manuscript. HK - DC - study concept and design; acquisition of data; statistical analysis; interpretation of data; drafting of the manuscript. NR 30 TC 1 Z9 1 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0036-5521 EI 1502-7708 J9 SCAND J GASTROENTERO JI Scand. J. Gastroenterol. PY 2015 VL 50 IS 11 BP 1382 EP 1388 DI 10.3109/00365521.2015.1050692 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CR4RL UT WOS:000361325000010 PM 25997458 ER PT J AU Wolthusen, RPF Hass, J Walton, E Turner, JA Rossner, V Sponheim, SR Ho, BC Holt, DJ Gollub, RL Calhoun, V Ehrlich, S AF Wolthusen, Rick P. F. Hass, Johanna Walton, Esther Turner, Jessica A. Roessner, Veit Sponheim, Scott R. Ho, Beng-Choon Holt, Daphne J. Gollub, Randy L. Calhoun, Vince Ehrlich, Stefan TI Genetic underpinnings of left superior temporal gyrus thickness in patients with schizophrenia SO WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY LA English DT Article DE genetics; imaging; schizophrenia; superior temporal gyrus; cortical thickness ID GENOME-WIDE ASSOCIATION; HUMAN CEREBRAL-CORTEX; DATA QUALITY-CONTROL; METABOLIC SYNDROME; ATYPICAL ANTIPSYCHOTICS; GLUCOSE-HOMEOSTASIS; CORTICAL THICKNESS; DIABETES-MELLITUS; PLANUM TEMPORALE; ZINC TRANSPORTER AB Objectives. Schizophrenia is a highly disabling psychiatric disorder with a heterogeneous phenotypic appearance. We aimed to further the understanding of some of the underlying genetics of schizophrenia, using left superior temporal gyrus (STG) grey matter thickness reduction as an endophenoptype in a genome-wide association (GWA) study. Methods. Structural magnetic resonance imaging (MRI) and genetic data of the Mind Clinical Imaging Consortium (MCIC) study of schizophrenia were used to analyse the interaction effects between 1,067,955 single nucleotide polymorphisms (SNPs) and disease status on left STG thickness in 126 healthy controls and 113 patients with schizophrenia. We next used a pathway approach to detect underlying pathophysiological pathways that may be related to schizophrenia. Results. No SNP by diagnosis interaction effect reached genome-wide significance (5 x 10(-8)) in our GWA study, but 10 SNPs reached P-values less than 10(-6). The most prominent pathways included those involved in insulin, calcium, PI3K-Akt and MAPK signalling. Conclusions. Our strongest findings in the GWA study and pathway analysis point towards an involvement of glucose metabolism in left STG thickness reduction in patients with schizophrenia only. These results are in line with recently published studies, which showed an increased prevalence of psychosis among patients with metabolic syndrome-related illnesses including diabetes. C1 [Wolthusen, Rick P. F.; Hass, Johanna; Walton, Esther; Roessner, Veit; Ehrlich, Stefan] Tech Univ Dresden, Fac Med Carl Gustav Carus, Dept Child & Adolescent Psychiat, Translat Dev Neurosci Sect, D-01062 Dresden, Germany. [Wolthusen, Rick P. F.; Holt, Daphne J.; Gollub, Randy L.; Ehrlich, Stefan] Massachusetts Gen Hosp, MGH MIT HMS Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Wolthusen, Rick P. F.; Holt, Daphne J.; Gollub, Randy L.; Ehrlich, Stefan] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Wolthusen, Rick P. F.] Harvard Univ, Sch Med, Div Med Sci, Boston, MA USA. [Hass, Johanna] Univ Tubingen, Inst Trop Med, Tubingen, Germany. [Walton, Esther] Kings Coll London, Inst Psychiat Psychol & Neurosci, London WC2R 2LS, England. [Turner, Jessica A.] Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA. [Turner, Jessica A.] Georgia State Univ, Inst Neurosci, Atlanta, GA 30303 USA. [Sponheim, Scott R.] Univ Minnesota, Dept Psychiat, Minneapolis VA Hlth Care Syst, Minneapolis, MN 55455 USA. [Ho, Beng-Choon] Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA. [Holt, Daphne J.; Gollub, Randy L.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Calhoun, Vince] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. [Calhoun, Vince] Mind Res Network, Albuquerque, NM USA. RP Wolthusen, RPF (reprint author), Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St,Room 2611, Charlestown, MA 02129 USA. EM RWolthusen@mgh.harvard.edu FU National Institutes of Health [NIH/NCRR P41RR14075]; Department of Energy [DE-FG02-99ER62764]; MIND Research Network, Morphometry Biomedical Informatics Research Network (BIRN) [1U24, RR021382A]; Function BIRN [U24RR021992-01, NIH.NCRR MO1 RR025758-01, NIMH 1RC1MH089257]; NARSAD Young Investigator Grant; Deutsche Forschungsgemeinschaft FX This work was supported by the National Institutes of Health (NIH/NCRR P41RR14075), Department of Energy (DE-FG02-99ER62764), MIND Research Network, Morphometry Biomedical Informatics Research Network (BIRN) (1U24, RR021382A), Function BIRN (U24RR021992-01, NIH.NCRR MO1 RR025758-01, NIMH 1RC1MH089257 to VDC), the NARSAD Young Investigator Grant (to SE), and the Deutsche Forschungsgemeinschaft (Research Fellowship to SE). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 84 TC 0 Z9 0 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1562-2975 EI 1814-1412 J9 WORLD J BIOL PSYCHIA JI World J. Biol. Psychiatry PY 2015 VL 16 IS 6 BP 430 EP 440 DI 10.3109/15622975.2015.1062915 PG 11 WC Psychiatry SC Psychiatry GA CR4TJ UT WOS:000361331700008 ER PT S AU Componation, PJ Dorneich, M Hansen, JL AF Componation, Paul J. Dorneich, Michael Hansen, Jordan L. BE Wade, J Cloutier, R TI Comparing Systems Engineering and Project Success in Commercial-focused versus Government-focused Projects SO 2015 CONFERENCE ON SYSTEMS ENGINEERING RESEARCH SE Procedia Computer Science LA English DT Proceedings Paper CT Conference on Systems Engineering Research CY MAR 17-19, 2015 CL Hoboken, NJ DE Systems Engineering; project management; project success metrics AB This work looks at the relationship between systems engineering and project success industry lead in aerospace, agriculture, defense & security, energy and related areas. The projects included both commercial-focused and government-focused efforts. Differences were found in both the overall risk levels and the measures of success for the two groups. In addition, government-focused projects showed a notably larger number of significant relationships between system engineering processes and project success than the commercial-focused projects. The research notes that further investigation is warranted, in particular looking at individual industry sectors, exploring the impact of team dispersion, and developing a better understanding of interrelationships between the systems engineering processes. This type of analysis will help further our understanding of both the art and science of systems engineering. (C) 2015 Published by Elsevier B.V. C1 [Componation, Paul J.] Univ Texas Arlington, IMSE Dept, Arlington, TX 76019 USA. [Dorneich, Michael] Iowa State Univ, IMSE Dept, Ames, IA 50011 USA. [Hansen, Jordan L.] VA Boston Healthcare Syst, New England VERC, Boston, MA USA. RP Componation, PJ (reprint author), Univ Texas Arlington, IMSE Dept, Box 19017,500 West First St, Arlington, TX 76019 USA. EM componation@uta.edu NR 13 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-0509 J9 PROCEDIA COMPUT SCI PY 2015 VL 44 BP 266 EP 274 DI 10.1016/j.procs.2015.03.006 PG 9 WC Computer Science, Information Systems; Computer Science, Software Engineering; Computer Science, Theory & Methods SC Computer Science GA BD4JE UT WOS:000360836300027 ER PT J AU Liang, SH Vasdev, N AF Liang, Steven H. Vasdev, Neil TI Total Radiosynthesis: Thinking Outside 'the Box' SO AUSTRALIAN JOURNAL OF CHEMISTRY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; GROWTH-FACTOR RECEPTOR; HIGH-YIELD SYNTHESIS; MONOAMINE-OXIDASE B; HUMAN BRAIN; 5-HT1A RECEPTORS; IRREVERSIBLE INHIBITOR; FLUORINE SUBSTITUTION; C-11 WAY-100635; EX-VIVO AB The logic of total synthesis transformed a stagnant state of chemistry when there was a paucity of methods and reagents to synthesize pharmaceuticals. Molecular imaging by positron emission tomography (PET) is now experiencing a renaissance in the way radiopharmaceuticals are synthesized; however, a paradigm shift is desperately needed in the radiotracer discovery pipeline to accelerate drug development. As with most drugs, most radiotracers also fail, therefore expeditious evaluation of tracers in preclinical models before optimization or derivatization of the lead molecules is necessary. Furthermore the exact position of the C-11 and F-18 radionuclide in tracers is often critical for metabolic considerations, and flexible methodologies to introduce radionuclides are needed. A challenge in PET radiochemistry is the limited choice of labelled building blocks available with carbon-11 (C-11; half-life similar to 20 min) and fluorine-18 (F-18; half-life similar to 2 h). In fact, most drugs cannot be labelled with C-11 or F-18 owing to a lack of efficient and diverse radiosynthetic methods. Routine radiopharmaceutical production generally relies on the incorporation of the isotope at the last or penultimate step of synthesis. Such reactions are conducted within the constraints of an automated synthesis unit ('box'), which has further stifled the exploration of multistep reactions with short-lived radionuclides. Radiopharmaceutical synthesis can be transformed by considering logic of total synthesis to develop novel approaches for C-11- and F-18-radiolabelling complex molecules via retrosynthetic analysis and multistep reactions. As a result of such exploration, new methods, reagents, and radiopharmaceuticals for in vivo imaging studies are discovered and are critical to work towards our ultimate, albeit impossible goal - a concept we term as total radiosynthesis - to radiolabel virtually any molecule. In this account, we show how multistep radiochemical reactions have impacted our radiochemistry program, with prominent examples from others, focusing on impact towards human imaging studies. As the goal of total synthesis is to be concise, we strive to simplify the syntheses of radiopharmaceuticals. New clinically useful strategies, including [C-11] CO2 fixation, which has enabled library radiosynthesis, as well as radiofluorination of non-activated arenes via iodonium ylides are highlighted. We also showcase state-of-the-art automation technologies, including microfluidic flow chemistry for radiopharmaceutical production. C1 [Liang, Steven H.; Vasdev, Neil] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Liang, Steven H.; Vasdev, Neil] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Vasdev, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nucl Med & Mol Imaging, 55 Fruit St, Boston, MA 02114 USA. EM vasdev.neil@mgh.harvard.edu FU NIDA NIH HHS [K01 DA038000] NR 69 TC 3 Z9 3 U1 1 U2 7 PU CSIRO PUBLISHING PI CLAYTON PA UNIPARK, BLDG 1, LEVEL 1, 195 WELLINGTON RD, LOCKED BAG 10, CLAYTON, VIC 3168, AUSTRALIA SN 0004-9425 EI 1445-0038 J9 AUST J CHEM JI Aust. J. Chem. PY 2015 VL 68 IS 9 BP 1319 EP 1328 DI 10.1071/CH15406 PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA CR0EF UT WOS:000360990400002 PM 27512156 ER PT J AU Huang, JW Dahl, DM Dong, L Liu, Q Cornejo, K Wang, Q Wu, SL Feldman, AS Huang, YR Xue, W Wu, CL AF Huang, Jiwei Dahl, Douglas M. Dong, Liang Liu, Qiang Cornejo, Kristine Wang, Qi Wu, Shulin Feldman, Adam S. Huang, Yiran Xue, Wei Wu, Chin-Lee TI Preoperative Neutrophil-to-Lymphocyte Ratio and Neutrophilia Are Independent Predictors of Recurrence in Patients with Localized Papillary Renal Cell Carcinoma SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID PROGNOSTIC-FACTOR; CANCER; VALIDATION; SURVIVAL; TUMORS AB Objective. To evaluate the role of preoperative neutrophil-to-lymphocyte ratio (NLR) and absolute neutrophil count (ANC) in patients' prognosis with localized papillary renal cell carcinoma (pRCC). Methods. Data from 218 localized pRCC patients (T1-3 N0/+ M0), operated between 1991 and 2011 at two centers, were evaluated retrospectively. Univariable and multivariable analyses using the Cox regression model were performed to determine the associations of NLR and ANC with recurrence-free survival (RFS). Prognostic accuracy was evaluated with the Harrell concordance index. Results. The 5-year RFS rate was 87.0%. Multivariable analysis identified increased NLR (>= 3.6) and ANC (>= 5300/mu L) as independent prognostic factors for RFS (hazard ratio (HR) = 4.01, P = 0.018) and (HR = 4.71, P = 0.045). The final model built by the addition of NLR or ANC improved predictive accuracy (c-index: 0.824, 0.842) compared with the clinicopathological base model (c-index: 0.800), which included TNM stage and tumor necrosis. Conclusions. The NLR and ANC appear to be independent prognostic factors for RFS after surgery for localized pRCC. They significantly increase the accuracy of established prognostic factors. Therefore, we recommend adding NLR and ANC to traditional prognostic model, which may improve its predictive accuracy. C1 [Huang, Jiwei; Dong, Liang; Huang, Yiran; Xue, Wei] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Urol, Shanghai 200123, Peoples R China. [Dahl, Douglas M.; Feldman, Adam S.; Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Dahl, Douglas M.; Cornejo, Kristine; Wang, Qi; Wu, Shulin; Feldman, Adam S.; Wu, Chin-Lee] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Liu, Qiang] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Pathol, Shanghai 200123, Peoples R China. [Cornejo, Kristine; Wu, Shulin; Wu, Chin-Lee] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wang, Qi] Boston Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Xue, W (reprint author), Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Urol, Shanghai 200123, Peoples R China. EM uroxuewei@163.com; cwu2@mgh.harvard.edu FU National Natural Science Foundation of China [81402084] FX The design and conduct of the project described were supported by Award no. 81402084 from the National Natural Science Foundation of China. NR 23 TC 2 Z9 2 U1 0 U2 0 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 2015 AR 891045 DI 10.1155/2015/891045 PG 9 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA CR3PZ UT WOS:000361246700001 ER PT J AU Chen, J Wang, MP Wang, X Viswanath, K Lam, TH Chan, SS AF Chen, Jing Wang, Man-Ping Wang, Xin Viswanath, Kasisomayajula Lam, Tai-Hing Chan, Sophia S. TI Secondhand smoke exposure (SHS) and health-related quality of life (HRQoL) in Chinese never smokers in Hong Kong SO BMJ OPEN LA English DT Article ID 2ND-HAND SMOKE; MENTAL-HEALTH; HEART-FAILURE; UNITED-STATES; CHILDREN; MORTALITY; OUTCOMES; SF-12V2; ASSOCIATION; ADOLESCENTS AB Objective: The evidence on the effect of secondhand smoke (SHS) on Health Related Quality of Life (HRQoL) is limited. We examined the relation between SHS and HRQoL among Chinese in Hong Kong. Methods: Adult never smokers from a probability sample of three cross-sectional waves (2010, 2012, 2013) of The Hong Kong Family and Health Information Trends Survey who completed the Cantonese-version of Short-Form 12 Health Survey Questionnaire (SF12v2) were included in the data analysis conducted in 2014. Models were used to examine associations of SHS with SF12 domains and summary scores of Physical (PCS12) and Mental Component (MCS12) with subgroups analysis by SHS locations. Results: After adjustments, SHS was associated with lower scores on all SF12 domains except physical functioning. PCS12 (regress coefficient=-0.76, 95% CI-1.34 to -0.17) and MCS12 (regress coefficient=-1.35, 95% CI -2.06 to -0.64) were lower in those with SHS exposure than those non-exposed. Those exposed to SHS in outdoor public places had lower scores on most SF12 domains and PSC12 and MCS12. SHS exposure in one's home and workplace was associated with lower scores on role physical, body pain and role emotional while SHS exposure in friends' homes was additionally associated with lower social functioning and mental health scores. Lower MCS12 was associated with SHS exposure at all locations except one's home. Conclusions: Our study showed that SHS exposure, particularly in outdoor public places, was associated with decreased HRQoL. It can provide new evidence for stronger smoke-free policies on public places and promoting smoke-free homes. C1 [Chen, Jing; Wang, Man-Ping; Chan, Sophia S.] Univ Hong Kong, Sch Nursing, Hong Kong, Hong Kong, Peoples R China. [Wang, Xin; Lam, Tai-Hing] Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China. [Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Ctr Community Based Res,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lam, TH (reprint author), Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China. EM hrmrlth@hku.hk FU Hong Kong Jockey Club Charities Trust FX This study was part of the project 'FAMILY: a Jockey Club Initiative for a Harmonious Society', funded by the Hong Kong Jockey Club Charities Trust. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 47 TC 0 Z9 0 U1 2 U2 6 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 2015 VL 5 IS 9 AR e007694 DI 10.1136/bmjopen-2015-007694 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CQ8MY UT WOS:000360863100043 PM 26338682 ER PT J AU Ladha, KS Zhao, KV Quraishi, SA Kurth, T Eikermann, M Kaafarani, HMA Klein, EN Seethala, R Lee, J AF Ladha, Karim S. Zhao, Kevin Quraishi, Sadeq A. Kurth, Tobias Eikermann, Matthias Kaafarani, Haytham M. A. Klein, Eric N. Seethala, Raghu Lee, Jarone TI The Deyo-Charlson and Elixhauser-van Walraven Comorbidity Indices as predictors of mortality in critically ill patients SO BMJ OPEN LA English DT Article ID INTENSIVE-CARE-UNIT; ADMINISTRATIVE DATA; RESOURCE USE; RECLASSIFICATION; SURVIVAL; ICD-9-CM; IMPACT; CANCER; COHORT AB Objectives: Our primary objective was to compare the utility of the Deyo-Charlson Comorbidity Index (DCCI) and Elixhauser-van Walraven Comorbidity Index (EVCI) to predict mortality in intensive care unit (ICU) patients. Setting: Observational study of 2 tertiary academic centres located in Boston, Massachusetts. Participants: The study cohort consisted of 59 816 patients from admitted to 12 ICUs between January 2007 and December 2012. Primary and secondary outcome: For the primary analysis, receiver operator characteristic curves were constructed for mortality at 30, 90, 180, and 365 days using the DCCI as well as EVCI, and the areas under the curve (AUCs) were compared. Subgroup analyses were performed within different types of ICUs. Logistic regression was used to add age, race and sex into the model to determine if there was any improvement in discrimination. Results: At 30 days, the AUC for DCCI versus EVCI was 0.65 (95% CI 0.65 to 0.67) vs 0.66 (95% CI 0.65 to 0.66), p= 0.02. Discrimination improved at 365 days for both indices (AUC for DCCI 0.72 (95% CI 0.71 to 0.72) vs AUC for EVCI 0.72 (95% CI 0.72 to 0.72), p= 0.46). The DCCI and EVCI performed similarly across ICUs at all time points, with the exception of the neurosciences ICU, where the DCCI was superior to EVCI at all time points (1-year mortality: AUC 0.73 (95% CI 0.72 to 0.74) vs 0.68 (95% CI 0.67 to 0.70), p= 0.005). The addition of basic demographic information did not change the results at any of the assessed time points. Conclusions: The DCCI and EVCI were comparable at predicting mortality in critically ill patients. The predictive ability of both indices increased when assessing long-term outcomes. Addition of demographic data to both indices did not affect the predictive utility of these indices. Further studies are needed to validate our findings and to determine the utility of these indices in clinical practice. C1 [Ladha, Karim S.; Zhao, Kevin; Quraishi, Sadeq A.; Eikermann, Matthias] Massachusetts Gen Hosp, Div Crit Care Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Ladha, Karim S.; Quraishi, Sadeq A.; Eikermann, Matthias] Harvard Univ, Dept Anaesthesia, Sch Med, Boston, MA 02115 USA. [Kurth, Tobias] INSERM, Res Ctr Epidemiol & Biostat U897, Bordeaux, France. [Kurth, Tobias] Univ Bordeaux, Coll Hlth Sci, Bordeaux, France. [Kaafarani, Haytham M. A.; Lee, Jarone] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Dept Surg, Boston, MA 02114 USA. [Kaafarani, Haytham M. A.; Lee, Jarone] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Klein, Eric N.] Hartford Hosp, Dept Surg, Hartford, CT 06115 USA. [Seethala, Raghu] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Lee, Jarone] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Lee, J (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Dept Surg, Boston, MA 02114 USA. EM lee.jarone@mgh.harvard.edu OI Kurth, Tobias/0000-0001-7169-2620 FU US National Institutes of Health [L30 GM102903, L30 TR001257, T32 GM007592]; Harvard Medical School; French National Research Agency; US National Institutes of Health; Masimo; MERCK; ResMed Foundation; Buzen's Foundation FX SAQ has received within the past 2 years investigator-initiated research funding from the US National Institutes of Health (grants L30 GM102903, L30 TR001257 and T32 GM007592) and Harvard Medical School. TK has received within the past 2 years investigator-initiated research funding from the French National Research Agency and the US National Institutes of Health. Further, he has received honoraria from the BMJ and Cephalalgia for editorial services. ME has received within the past 2 years investigator-initiated research funding from Masimo, MERCK, the ResMed Foundation, and the Buzen's Foundation. Further, he has received honoraria from the journal Anesthesiology for editorial services. NR 25 TC 6 Z9 6 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 2015 VL 5 IS 9 AR e008990 DI 10.1136/bmjopen-2015-008990 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CQ8MY UT WOS:000360863100019 PM 26351192 ER PT J AU Hanson, AJ Bayer, JL Baker, LD Cholerton, B VanFossen, B Trittschuh, E Rissman, RA Donohue, MC Moghadam, SH Plymat, SR Craft, S AF Hanson, Angela J. Bayer, Jennifer L. Baker, Laura D. Cholerton, Brenna VanFossen, Brian Trittschuh, Emily Rissman, Robert A. Donohue, Michael C. Moghadam, Setareh H. Plymat, Stephen R. Craft, Suzanne TI Differential Effects of Meal Challenges on Cognition, Metabolism, and Biomarkers for Apolipoprotein E epsilon 4 Carriers and Adults with Mild Cognitive Impairment SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; APOE genotype; glycemic index; insulin; plasma amyloid; saturated fat; triglycerides ID ALZHEIMERS-DISEASE RISK; TRANSGENIC MOUSE MODEL; INSULIN-RESISTANCE; DIETARY PATTERNS; OXIDATIVE STRESS; HIGH-FAT; E GENOTYPE; DEMENTIA; PLASMA; POPULATION AB Background: High intake of saturated fat (SF) and glycemic index (GI) foods is a risk factor for sporadic Alzheimer's disease. Meal challenges may elucidate mechanisms that contribute to this risk, enabling development of targeted interventions. Objective: To assess cognitive and metabolic changes after a meal high in SF and GI calories (HIGH) versus a meal low in these macronutrients (LOW) in older adults with and without cognitive impairment, and with and without the apolipoprotein E4 risk factor. Methods: 46 adults with either cognitive impairment (CI) or normal cognition (NC) ingested a LOW (25% total fat, 7% SF, GI <55) and a HIGH meal (50% total fat, 25% SF, GI >70) in a blinded random fashion. Participants then underwent cognitive testing and blood sampling for metabolic and Alzheimer's disease biomarkers. Data were analyzed using repeated measures ANOVA and Spearman correlations. Results: E4-adults with NC demonstrated lower delayed memory scores after the HIGH compared to the LOW meal, whereas normal E4+ and CI E4- groups had higher scores after the HIGH meal (ANOVA p = 0.03). These findings were associated with meal-induced changes in glucose (p = 0.05), insulin (p = 0.004), triglycerides (p < 0.01), and plasma A beta(42) (p = 0.05). Conclusions: These preliminary data suggest that cognitive performance of adults without CI mayworsen following high SF and sugar meals, whereas adults with CI or those at risk for CI due to E4 status may benefit acutely from such meals. Furthermore, plasma A beta was affected by meal type, suggesting a relationship between metabolic response and amyloid regulation. C1 [Hanson, Angela J.; Cholerton, Brenna] Univ Washington, Med Ctr, Dept Med, Seattle, WA 98195 USA. [Bayer, Jennifer L.] Univ Iowa, Iowa City, IA USA. [Baker, Laura D.; Craft, Suzanne] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Sticht Ctr Aging, Winston Salem, NC 27157 USA. [VanFossen, Brian; Trittschuh, Emily] VA Puget Sound Healthcare Syst, Seattle, WA USA. [Rissman, Robert A.; Donohue, Michael C.; Moghadam, Setareh H.] Univ Calif San Diego, Dept Neurosci, Alzheimers Dis Cooperat Study, La Jolla, CA 92093 USA. RP Craft, S (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Sticht Ctr Aging, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM suzcraft@wakehealth.edu FU AFAR Hartford Center of Excellence Award [AG010483, AG032755]; Alzheimer's Disease Cooperative Study (ADCS) Biomarker core from the National Institute on Aging; National Institute on Aging [R37 AG 10880]; [5T32AG000258] FX This research was supported by grant 5T32AG000258 training grant and AFAR Hartford Center of Excellence Award to Dr. Hanson, grants AG010483 and AG032755 and the Alzheimer's Disease Cooperative Study (ADCS) Biomarker core from the National Institute on Aging to Dr. Rissman and Dr. Donohue, and R37 AG 10880 from the National Institute on Aging to Dr. Craft. This article results from work supported by resources from the Veterans Affairs Puget Sound Health Care System, Seattle, Washington. NR 55 TC 4 Z9 4 U1 5 U2 11 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2015 VL 48 IS 1 BP 205 EP 218 DI 10.3233/JAD-150273 PG 14 WC Neurosciences SC Neurosciences & Neurology GA CQ9JW UT WOS:000360931700019 PM 26401941 ER PT J AU Wood, PL Medicherla, S Sheikh, N Terry, B Phillipps, A Kaye, JA Quinn, JF Woltjer, RL AF Wood, Paul L. Medicherla, Srikanth Sheikh, Naveen Terry, Bradley Phillipps, Aaron Kaye, Jeffrey A. Quinn, Joseph F. Woltjer, Randall L. TI Targeted Lipidomics of Fontal Cortex and Plasma Diacylglycerols (DAG) in Mild Cognitive Impairment and Alzheimer's Disease: Validation of DAG Accumulation Early in the Pathophysiology of Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; diacylglycerols; mild cognitive impairment; monoacylglycerols ID LIPOPROTEIN-LIPASE; FRONTAL-CORTEX; HUMAN BRAIN; DEMENTIA; ENZYMES; METABOLISM; ACTIVATION; PROTEINS; POLARITY; COMPLEX AB Previous studies have demonstrated augmented levels of diacylglycerols (DAG) in the frontal cortex and plasma of Alzheimer's disease (AD) patients. We extended these findings from non-targeted lipidomics studies to design a lipidomics platform to interrogate DAGs and monoacylglycerols (MAG) in the frontal cortex and plasma of MCI subjects. Control subjects included both aged normal controls and controls with normal cognition, but AD pathology at autopsy, individuals termed non-demented AD neuropathology. DAGs with saturated, unsaturated, and polyunsaturated fatty acid substituents were found to be elevated in MCI frontal cortex and plasma. Tandem mass spectrometry of the DAGs did not reveal any differences in the distributions of the fatty acid substitutions between MCI and control subjects. While triacylglycerols were not altered in MCI subjects there were increases in MAG levels both in the frontal cortex and plasma. In toto, increased levels of DAGs and MAGs appear to occur early in AD pathophysiology and require both further validation in a larger patient cohort and elucidation of the lipidomics alteration(s) that lead to the accumulation of DAGs in MCI subjects. C1 [Wood, Paul L.; Medicherla, Srikanth; Sheikh, Naveen; Terry, Bradley; Phillipps, Aaron] Lincoln Mem Univ, Lipid Unit, Dept Physiol & Pharmacol, DeBusk Coll Osteopath Med, Harrogate, TN 37752 USA. [Kaye, Jeffrey A.; Quinn, Joseph F.; Woltjer, Randall L.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR USA. [Kaye, Jeffrey A.; Quinn, Joseph F.; Woltjer, Randall L.] Portland VA Med Ctr, Portland, OR USA. RP Wood, PL (reprint author), Lincoln Mem Univ, Lipid Unit, Dept Physiol & Pharmacol, DeBusk Coll Osteopath Med, 6965 Cumberland Gap Pkwy, Harrogate, TN 37752 USA. EM paul.wood@lmunet.edu FU Lincoln Memorial University, DeBusk College of Osteopathic Medicine; [NIA-AG08017] FX We thank the participants of the aging study and their families for their valuable contribution to aging and Alzheimer's disease research. This research was funded by Lincoln Memorial University, DeBusk College of Osteopathic Medicine and by NIA-AG08017. NR 48 TC 5 Z9 5 U1 0 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2015 VL 48 IS 2 BP 537 EP 546 DI 10.3233/JAD-150336 PG 10 WC Neurosciences SC Neurosciences & Neurology GA CR1EI UT WOS:000361066200022 PM 26402017 ER PT J AU Salameh, TS Bullock, KM Hujoel, IA Niehoff, ML Wolden-Hanson, T Kim, J Morley, JE Farr, SA Banks, WA AF Salameh, Therese S. Bullock, Kristin M. Hujoel, Isabel A. Niehoff, Michael L. Wolden-Hanson, Tami Kim, Junghyun Morley, John E. Farr, Susan A. Banks, William A. TI Central Nervous System Delivery of Intranasal Insulin: Mechanisms of Uptake and Effects on Cognition SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; cognition; insulin; intranasal administration ID BLOOD-BRAIN-BARRIER; SENESCENCE-ACCELERATED MICE; GROWTH-FACTOR EXPRESSION; AGED SAMP8 MOUSE; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; RAT-BRAIN; ANTISENSE OLIGONUCLEOTIDE; MEMORY IMPAIRMENT; APOE GENOTYPE AB Intranasal insulin has shown efficacy in patients with Alzheimer's disease (AD), but there are no preclinical studies determining whether or how it reaches the brain. Here, we showed that insulin applied at the level of the cribriform plate via the nasal route quickly distributed throughout the brain and reversed learning and memory deficits in an AD mouse model. Intranasal insulin entered the blood stream poorly and had no peripheral metabolic effects. Uptake into the brain from the cribriform plate was saturable, stimulated by PKC inhibition, and responded differently to cellular pathway inhibitors than did insulin transport at the blood-brain barrier. In summary, these results show intranasal delivery to be an effective way to deliver insulin to the brain. C1 [Salameh, Therese S.; Bullock, Kristin M.; Hujoel, Isabel A.; Wolden-Hanson, Tami; Banks, William A.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Salameh, Therese S.; Banks, William A.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA. [Niehoff, Michael L.; Kim, Junghyun; Morley, John E.; Farr, Susan A.] St Louis Univ, Dept Internal Med, Div Geriatr, St Louis, MO 63103 USA. [Niehoff, Michael L.; Farr, Susan A.] Vet Affairs Med Ctr St Louis, St Louis, MO USA. RP Banks, WA (reprint author), VAPSHCS, 810A-1,1660 S Columbian Way, Seattle, WA 98108 USA. EM wabanks1@uw.edu FU National Institutes of Health National Institute on Aging [R01-AG046619, T32-AG000258] FX This work was supported by the National Institutes of Health National Institute on Aging (Grant R01-AG046619). Therese S. Salameh is supported by National Institutes of Health National Institute on Aging (Grant T32-AG000258). We would like to acknowledge the Rodent Metabolic and Behavioral Phenotyping Core at the VA Puget Sound Health Care System. NR 44 TC 10 Z9 10 U1 5 U2 18 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2015 VL 47 IS 3 BP 715 EP 728 DI 10.3233/JAD-150307 PG 14 WC Neurosciences SC Neurosciences & Neurology GA CQ9JN UT WOS:000360930700017 PM 26401706 ER PT J AU Li, G Xiong, KP Korff, A Pan, C Quinn, JF Galasko, DR Liu, CF Montine, TJ Peskind, ER Zhang, J AF Li, Ge Xiong, Kangping Korff, Ane Pan, Catherine Quinn, Joseph F. Galasko, Douglas R. Liu, Chunfeng Montine, Thomas J. Peskind, Elaine R. Zhang, Jing TI Increased CSF E-Selectin in Clinical Alzheimer's Disease without Altered CSF A beta(42) and Tau SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; A beta(42); cerebrospinal fluid; biomarkers; cerebrovascular disease; E-selectin; tau; vascular cell adhesion molecule 1 ID SILENT CEREBRAL INFARCTION; SOLUBLE ADHESION MOLECULES; DEMENTIA; NEUROPATHOLOGY; ASSOCIATION; AUTOPSY; INJURY; AD AB Clinically diagnosed Alzheimer's disease (AD) is pathologically heterogeneous. In this multicenter cohort of 215 clinically diagnosed AD patients and 249 controls, E-selectin and vascular cell adhesion molecule 1 (VACM-1) were measured along with amyloid-beta peptide 1-42 (A beta(42)) and tau. We discovered that E-selectin, a biomarker of endothelial function/vascular injury, was inversely correlated with cerebrospinal fluid (CSF) tau/A beta(42) ratio and significantly elevated in clinical AD patients without the typical AD CSF biomarker signature (i.e., low tau/A beta(42) ratio) compared to those with the signature. These findings suggest that E-selectin may be an objective biomarker related to vascular mechanisms contributing to dementia. C1 [Li, Ge; Peskind, Elaine R.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Xiong, Kangping; Liu, Chunfeng] Soochow Univ, Affiliated Hosp 2, Dept Neurol, Suzhou, Peoples R China. [Korff, Ane; Pan, Catherine; Zhang, Jing] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98104 USA. [Quinn, Joseph F.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Quinn, Joseph F.] Portland VA Med Ctr, Portland, OR USA. [Galasko, Douglas R.; Montine, Thomas J.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Li, Ge] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Peskind, Elaine R.] Vet Affairs Puget Sound Hlth Care Syst, VA Northwest Network Mental Illness Res Educ & Cl, Seattle, WA USA. RP Zhang, J (reprint author), Univ Washington, Dept Pathol, 325 9th Ave, Seattle, WA 98104 USA. EM zhangj@uw.edu FU Shaw endowment; Department of Veterans Affairs; [AG05136]; [AG023185]; [AG08017]; [NS082137] FX We appreciate deeply the assistance provided by Ms. Jane Shofer and Dr. Travis Cook in the preparation of the manuscript. The work was supported by several grants (AG05136, AG023185, AG08017 and NS082137), an anonymous foundation, the Shaw endowment, and the Department of Veterans Affairs. NR 20 TC 1 Z9 1 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2015 VL 47 IS 4 BP 883 EP 887 DI 10.3233/JAD-150420 PG 5 WC Neurosciences SC Neurosciences & Neurology GA CQ9JS UT WOS:000360931300008 PM 26401768 ER PT J AU Quiroz, YT Willment, KC Castrillon, G Muniz, M Lopera, F Budson, A Stern, CE AF Quiroz, Yakeel T. Willment, Kim Celone Castrillon, Gabriel Muniz, Martha Lopera, Francisco Budson, Andrew Stern, Chantal E. TI Successful Scene Encoding in Presymptomatic Early-Onset Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; autosomal-dominant; functional MRI; memory encoding; presenilin-1 ID MILD COGNITIVE IMPAIRMENT; HIPPOCAMPAL ACTIVATION; DEMENTIA; RISK; RELIABILITY; DEPOSITION; PATTERNS; CAUDATE AB Background: Brain regions critical to episodic memory are altered during the preclinical stages of Alzheimer's disease (AD). However, reliable means of identifying cognitively-normal individuals at higher risk to develop AD have not been established. Objective: To examine whether functional MRI can detect early functional changes associated with scene encoding in a group of presymptomatic presenilin-1 (PSEN1) E280A mutation carriers. Methods: Participants were 39 young, cognitively-normal individuals from an autosomal dominant early-onset AD kindred, located in Antioquia, Colombia. Participants performed a functional MRI scene encoding task and a post-scan subsequent memory test. Results: PSEN1 mutation carriers exhibited hyperactivation within medial temporal lobe regions (hippocampus, parahippocampal formation) during successful scene encoding compared to age-matched non-carriers. Conclusion: Hyperactivation in medial temporal lobe regions during scene encoding is seen in individuals genetically-determined to develop AD years before their clinical onset. Our findings will guide future research with the ultimate goal of using functional neuroimaging in the early detection of preclinical AD. C1 [Quiroz, Yakeel T.; Lopera, Francisco] Univ Antioquia, Grp Neurociencias, Medellin, Colombia. [Quiroz, Yakeel T.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Willment, Kim Celone; Muniz, Martha] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Castrillon, Gabriel] Inst Alta Tecnol Med IATM, Medellin, Colombia. [Stern, Chantal E.] Boston Univ, Dept Psychol & Brain Sci, Ctr Memory & Brain, Boston, MA 02215 USA. [Budson, Andrew] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02215 USA. [Stern, Chantal E.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Quiroz, YT (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,Suite 701, Boston, MA 02114 USA. EM yquiroz@mgh.harvard.edu FU Boston University Center for Neuroscience; Department of Psychology; Boston University Alzheimer's Disease Center pilot award [P30AG13846]; National Institute of Neurological Disorders and Stroke [F31-NS078786-01A1]; National Institute of Health-Office of the Director [DP5OD019833]; COLCIENCIAS-Colombia [1115-408-20512, 1115-545-31651] FX This study was supported by the Boston University Center for Neuroscience (to CES), Department of Psychology (to CES and YTQ), a Boston University Alzheimer's Disease Center pilot award (P30AG13846 to CES and AB), the National Institute of Neurological Disorders and Stroke (F31-NS078786-01A1 to YTQ), the National Institute of Health-Office of the Director (DP5OD019833 to YTQ), COLCIENCIAS-Colombia (Projects: 1115-408-20512, 1115-545-31651 to FL), and an Anonymous Organization (FL). The authors thank the Instituto de Alta Tecnologia Medica (IATM) staff for their help with data acquisition. We thank the PSEN1 Colombian families for contributing their valuable time and effort, without which this study would not have been possible. NR 38 TC 1 Z9 1 U1 1 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2015 VL 47 IS 4 BP 955 EP 964 DI 10.3233/JAD-150214 PG 10 WC Neurosciences SC Neurosciences & Neurology GA CQ9JS UT WOS:000360931300014 PM 26401774 ER PT J AU Mendez, MF Paholpak, P Lin, A Zhang, JY Teng, E AF Mendez, Mario F. Paholpak, Pongsatorn Lin, Andrew Zhang, Jeannie Y. Teng, Edmond TI Prevalence of Traumatic Brain Injury in Early Versus Late-Onset Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Aging; Alzheimer's disease; concussion; dementia; epidemiology; head injury; memory loss; neurodegeneration; risk factors; traumatic brain injury ID HEAD-INJURY; RISK-FACTOR; DEMENTIA; AGE; ENCEPHALOPATHY; POPULATION; INDIVIDUALS; TAUOPATHY; AD AB Background: Traumatic brain injury (TBI) is the most established environmental risk factor for Alzheimer's disease (AD), but it is unclear if TBI is specifically associated with early-onset AD (EOAD). Objective: To evaluate the relationship between TBI and EOAD (<65 years). Methods: We identified 1,449 EOAD, 4,337 late-onset AD (LOAD), and corresponding EOAD-matched and LOAD-matched normal controls (NC) in the National Alzheimer's Coordinating Center Uniform (NACC) database and compared the prevalence of any history of TBI as well as measures of cognition, function, behavior, and neuropathology. For validation, we determined TBI prevalence among 115 well-characterized clinic patients with EOAD. Results: Part A: The prevalence of any TBI in the NACC-database EOAD participants (13.3%) was comparable to that observed in the clinic EOAD patients (13.9%) but significantly higher than in the NACC-database LOAD participants (7.7%; p < 0.0001) and trended to higher compared to EOAD-matched NC (11.1%; logistic regression p = 0.053). Part B: When we compared EOAD patients with documented non-acute and non-residually impairing TBI to EOAD without a documented history of prior TBI, those with TBI had significantly more disinhibition. Part C: Autopsies did not reveal differences in AD neuropathology based on a history of TBI. Conclusions: These findings suggest, but do not establish, that TBI is a specific risk factor for EOAD and may lead to disinhibition, a feature that often results from the frontal effects of head injury. This study recommends further research on the effects of TBI in EOAD in larger numbers of participants. C1 [Mendez, Mario F.; Paholpak, Pongsatorn; Lin, Andrew; Teng, Edmond] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Mendez, Mario F.; Paholpak, Pongsatorn; Lin, Andrew; Zhang, Jeannie Y.; Teng, Edmond] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Mendez, Mario F.; Paholpak, Pongsatorn; Lin, Andrew; Teng, Edmond] VA Greater Los Angeles Healthcare Syst, Neurobehav Unit, Dept Neurol, Los Angeles, CA USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Ctr, Neurobehav Unit, 691-116AF,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@UCLA.edu FU Medical Student Training in Aging Research Program, the National Institute on Aging [T35AG026736]; John A. Hartford Foundation; Lillian R. Gleitsman Foundation; NIA [U01 AG016976, P30 AG019610, P30 AG013846, P50 AG008702, P50 AG025688, P30 AG010133, P50 AG005146, P50 AG005134, P50 AG016574, P50 AG005138, P30 AG008051, P30 AG013854, P30 AG008017]; NIA/NIH [U01 AG016976]; The NIA [P30 AG010161, P30 AG010129, P50 AG016573, P50 AG016570, P50 AG005131, P50 AG023501, P30 AG035982, P30 AG028383, P30 AG010124, P50 AG005133, P50 AG005142, P30 AG012300, P50 AG005136, P50 AG033514, P50 AG005681] FX This research was funded by The Medical Student Training in Aging Research Program, the National Institute on Aging (T35AG026736), the John A. Hartford Foundation, the Lillian R. Gleitsman Foundation, and NIA Grant U01 AG016976.; The authors thank Michelle Mather, Kate Heller, and Dr. Stephen Hawes for their contributions. The NACC database is funded by NIA/NIH Grant U01 AG016976. NACC data are contributed by the NIA funded ADCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P50 AG005134 (PI Bradley Hyman, MD, PhD), P50 AG016574 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Steven Ferris, PhD), P30 AG013854 (PI M. Marsel Mesulam, MD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P50 AG016570 (PI David Teplow, PhD), P50 AG005131 (PI Douglas Galasko, MD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P50 AG005136 (PI Thomas Montine, MD, PhD), P50 AG033514 (PI Sanjay Asthana, MD, FRCP), and P50 AG005681 (PI John Morris, MD). NR 51 TC 3 Z9 3 U1 4 U2 16 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2015 VL 47 IS 4 BP 985 EP 993 DI 10.3233/JAD-143207 PG 9 WC Neurosciences SC Neurosciences & Neurology GA CQ9JS UT WOS:000360931300017 PM 26401777 ER PT J AU Gleason, CE Fischer, BL Dowling, NM Setchell, KDR Atwood, CS Carlsson, CM Asthana, S AF Gleason, Carey E. Fischer, Barbara L. Dowling, N. Maritza Setchell, Kenneth D. R. Atwood, Craig S. Carlsson, Cynthia M. Asthana, Sanjay TI Cognitive Effects of Soy Isoflavones in Patients with Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; clinical trial; cognition; daidzein; equol; genistein; phytoestrogens; soy isoflavones ID ESTROGEN-RECEPTOR-BETA; EQUOL-PRODUCER STATUS; POSTMENOPAUSAL WOMEN; OXIDATIVE STRESS; CONTROLLED-TRIAL; DOUBLE-BLIND; OLDER WOMEN; S-EQUOL; PHARMACOKINETICS; GENISTEIN AB Background: In a previous trial, treatment with soy isoflavones was associated with improved nonverbal memory, construction abilities, verbal fluency, and speeded dexterity compared to treatment with placebo in cognitively healthy older adults. Objective: The current trial aimed to examine the potential cognitive benefits of soy isoflavones in patients with Alzheimer's disease. Methods: Sixty-five men and women over the age of 60 were treated with 100 mg/day soy isoflavones, or matching placebo capsules for six months. APOE genotype was determined for all participants. Cognitive outcomes and plasma isoflavone levels were measured at baseline, and at two additional time points: three and six months after baseline. Results: Of the sixty-five participants enrolled, thirty-four (52.3%) were women, and 31 (47.7%) were APOE epsilon 4 positive. Average age was 76.3 (SD = 7.2) years. Fifty-nine (90.8%) subjects completed all study visits. Plasma isoflavone levels increased in subjects treated with soy isoflavones compared to baseline and to placebo, although intersubject variability in plasma levels was large. No significant differences in treatment effects for cognition emerged between treatment groups or genders. Exploratory analyses of associations between changes in cognition and plasma isoflavone levels revealed an association between equol levels, and speeded dexterity and verbal fluency. Conclusions: Six months of 100 mg/day treatment with soy isoflavones did not benefit cognition in older men and women with Alzheimer's disease. However, our results suggest the need to examine the role of isoflavone metabolism, i.e., the ability to effectively metabolize soy isoflavones by converting daidzen to equol when attempting to fully clarify the cognitive effects of isoflavones. C1 [Gleason, Carey E.; Fischer, Barbara L.; Atwood, Craig S.; Carlsson, Cynthia M.; Asthana, Sanjay] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Div Geriatr & Gerontol, Madison, WI USA. [Gleason, Carey E.; Fischer, Barbara L.; Atwood, Craig S.; Carlsson, Cynthia M.; Asthana, Sanjay] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Gleason, Carey E.; Dowling, N. Maritza; Carlsson, Cynthia M.; Asthana, Sanjay] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Dis Res Ctr, Madison, WI USA. [Dowling, N. Maritza] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA. [Setchell, Kenneth D. R.] Univ Cincinnati, Dept Pediat, Div Pathol & Lab Med, Cincinnati, OH USA. RP Gleason, CE (reprint author), Madison VA GRECC 11G, 2500 Overlook Terrace, Madison, WI 53705 USA. EM ceg@medicine.wisc.edu FU NIH [K23 AG024302, P50 AG033514] FX This research was supported by funding from the NIH (K23 AG024302; P50 AG033514). NR 58 TC 4 Z9 4 U1 2 U2 8 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2015 VL 47 IS 4 BP 1009 EP 1019 DI 10.3233/JAD-142958 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CQ9JS UT WOS:000360931300019 PM 26401779 ER PT J AU Parham, LR Briley, LP King, KS Byrne, J Rappold, E Goss, PE Spraggs, CF AF Parham, Laura R. Briley, Linda P. King, Karen S. Byrne, Julie Rappold, Erica Goss, Paul E. Spraggs, Colin F. TI Rash in lapatinib-treated patients is not associated with human leukocyte antigen polymorphisms SO PHARMACOGENOMICS LA English DT Article DE HLA polymorphisms; lapatinib; rash AB Rash is a common side effect of lapatinib treatment. Since human leukocyte antigen (HLA) alleles have been implicated in multiple drug-induced cutaneous reactions, this study investigated the association of HLA alleles with lapatinib-induced rash. 1191 participants from a large lapatinib monotherapy trial underwent HLA genotyping, and allele carriage frequencies between rash cases and controls were compared. This analysis had adequate power to detect an association of common HLA alleles with rash, similar to those reported previously. No HLA alleles were significantly associated with lapatinib-induced rash, including the previously identified lapatinib hepatotoxicity biomarker HLA-DRB1*07:01 (p = 0.87). The present study is consistent with the view that lapatinib-induced rash is not the consequence of HLA-restricted, immune-mediated mechanisms. C1 [Parham, Laura R.; Briley, Linda P.; King, Karen S.] PAREXEL Int, Res Triangle Pk, NC USA. [Parham, Laura R.; Briley, Linda P.; King, Karen S.; Byrne, Julie; Rappold, Erica] GlaxoSmithKline, London, England. [Rappold, Erica] Novartis Pharmaceut, E Hanover, NJ USA. [Goss, Paul E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Spraggs, Colin F.] GlaxoSmithKline Res & Dev Ltd, Medicines Res Ctr, Stevenage SG1 2NY, Herts, England. RP Spraggs, CF (reprint author), GlaxoSmithKline Res & Dev Ltd, Medicines Res Ctr, Gunnels Wood Rd, Stevenage SG1 2NY, Herts, England. EM colin.f.spraggs@gsk.com FU GlaxoSmithKline Pharmaceuticals, PA, USA; Avon Foundation, NY, USA; GlaxoSmithKline FX This work was supported by GlaxoSmithKline Pharmaceuticals, PA, USA. LR Parham, LP Briley, KS King, E Rappold, J Byrne and CF Spraggs are current or former employees of GlaxoSmithKline and own company stock. PE Goss is supported in part by The Avon Foundation, NY, USA. Minor editorial support was provided by Fishawack Indicia Ltd (funded by GlaxoSmithKline). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 5 TC 0 Z9 0 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 EI 1744-8042 J9 PHARMACOGENOMICS JI Pharmacogenomics PY 2015 VL 16 IS 11 BP 1227 EP 1229 DI 10.2217/pgs.15.69 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA CR2FP UT WOS:000361142000002 PM 26265235 ER PT J AU Buscariollo, DL Mamon, HJ AF Buscariollo, Daniela L. Mamon, Harvey J. TI Optimal management of resectable gastric adenocarcinoma SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE chemoradiation; chemotherapy; gastric adenocarcinoma; locally advanced; multimodality therapy; radiation therapy; respectable; stomach cancer ID LYMPH-NODE DISSECTION; PHASE-III TRIAL; RANDOMIZED CONTROLLED-TRIAL; ADJUVANT CHEMOTHERAPY; PREOPERATIVE CHEMORADIOTHERAPY; PERIOPERATIVE CHEMOTHERAPY; PATHOLOGICAL RESPONSE; CURATIVE RESECTION; RADIATION-THERAPY; CANCER SURVIVAL AB The worldwide incidence of gastric adenocarcinoma has rapidly declined in the past century, but gastric cancer remains the fifth most common malignancy in the world. Approximately half of all cases of gastric cancer are diagnosed in Eastern Asia. In this review, we provide an overview of the landmark studies investigating neoadjuvant and adjuvant therapies in resectable gastric cancer and highlight ongoing efforts to define optimal population-adapted management strategies. C1 [Buscariollo, Daniela L.; Mamon, Harvey J.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Harvard Radiat Oncol Program, Boston, MA 02215 USA. RP Mamon, HJ (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Harvard Radiat Oncol Program, 75 Francis St, Boston, MA 02215 USA. EM hmamon@lroc.harvard.edu NR 73 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1473-7140 EI 1744-8328 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PY 2015 VL 15 IS 8 BP 931 EP 941 DI 10.1586/14737140.2015.1054814 PG 11 WC Oncology SC Oncology GA CQ5LY UT WOS:000360647000009 PM 26165449 ER PT J AU Daifalla, NS Bayih, AG Gedamu, L AF Daifalla, Nada S. Bayih, Abebe Genetu Gedamu, Lashitew TI Differential Immune Response against Recombinant Leishmania donovani Peroxidoxin 1 and Peroxidoxin 2 Proteins in BALB/c Mice SO JOURNAL OF IMMUNOLOGY RESEARCH LA English DT Article ID STRESS-INDUCIBLE PROTEIN-1; GLUTATHIONE-S-TRANSFERASE; CPG OLIGODEOXYNUCLEOTIDES; CUTANEOUS LEISHMANIASIS; MURINE LEISHMANIASIS; INTERFERON-GAMMA; DENDRITIC CELLS; FUSION PROTEINS; INFECTION; PROTECTION AB We assessed the immune response against recombinant proteins of two related, albeit functionally different, peroxidoxins from Leishmania donovani: peroxidoxin 1 (LdPxn1) and peroxidoxin 2 (LdPxn2) in BALB/c mice. We also evaluated the effect of coadministration of TLR agonists (CpG ODN and GLA-SE) on the antigen-specific immune response. Immunization with recombinant LdPxn1 alone induced a predominantly Th2 type immune response that is associated with the production of high level of IgG1 and no IgG2a isotype while rLdPxn2 resulted in a mixed Th1/Th2 response characterized by the production of antigen-specific IgG2a in addition to IgG1 isotype. Antigen-stimulated spleen cells from mice that were immunized with rLdPxn1 produced low level of IL-10 and IL-4 and no IFN-gamma, whereas cells from mice immunized with rLdPxn2 secreted high level of IFN-gamma, low IL-4, and no IL-10. Coadministration of CpG ODN or GLA-SE with rLdPxn1 skewed the immune response towards a Th 1 type as indicated by robust production of IgG2a isotype. Furthermore, the presence of TLR agonists together with rLdPxn1 antigen enhanced the production of IFN-gamma and to a lesser extent of IL-10. TLR agonists also enhanced a more polarized Th1 type immune response against rLdPxn2. C1 [Daifalla, Nada S.; Bayih, Abebe Genetu; Gedamu, Lashitew] Univ Calgary, Dept Biol Sci, Calgary, AB T2N 1N4, Canada. [Daifalla, Nada S.] Forsyth Inst, Cambridge, MA 02142 USA. RP Gedamu, L (reprint author), Univ Calgary, Dept Biol Sci, Room 374,2500 Univ Dr NW, Calgary, AB T2N 1N4, Canada. EM lgedamu@ucalgary.ca RI Daifalla, Nada/E-6005-2017 FU Canadian Institute of Health Research (CIHR) [FRN 64318] FX The authors would like to thank Dr. Stephen Barr for cloning LdPxn1 and LdPxn2 in bacterial expression vector. The authors acknowledge Dr. Steve Reed, Infectious Diseases Research Institute, USA, for providing us with GLA-SE adjuvant. The authors also thank Mr. Michael Collier for helping with mice injection. This work was supported by a grant from Canadian Institute of Health Research (CIHR) to Dr. Lashitew Gedamu (FRN 64318). NR 40 TC 1 Z9 1 U1 1 U2 2 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 2314-8861 EI 2314-7156 J9 J IMMUNOL RES JI J Immunol. Res. PY 2015 AR 348401 DI 10.1155/2015/348401 PG 11 WC Immunology SC Immunology GA CQ6XO UT WOS:000360747600001 ER PT J AU Gunel, C Basak, HS Bleier, BS AF Gunel, C. Basak, H. S. Bleier, B. S. TI Oral steroids and intraoperative bleeding during endoscopic sinus surgery SO B-ENT LA English DT Article DE Chronic rhinosinusitis; osteitis; corticosteroids; nasal polyps; surgical blood loss; surgical field ID CHRONIC RHINOSINUSITIS; NASAL POLYPOSIS; OSTEITIS; ETHMOIDECTOMY; COMPLICATIONS; HEMOSTASIS; ADRENALINE; SCORE AB Objectives: Our main objective was to investigate the effect of preoperative oral steroids on intraoperative bleeding and quality of the surgical field during endoscopic sinus surgery (ESS). Our second objective was to determine whether the osteitis score could be used to predict the volume of intraoperative bleeding. Methodology: This double-blinded, randomized trial included 65 patients with chronic rhinosinusitis with nasal polyps. The corticosteroid group received oral prednisolone (1 mg/kg), administered to patients once daily for 2 days and then tapered down, with treatment completed on the day 10. The control group received placebo before the operation. Endoscopic exams were recorded, and preoperative sinus computed tomography scans were scored. Intraoperative blood loss was recorded. Quality of the surgical field was assessed by the surgeon, using a linear scale from 1 to 10. Results: The mean bleeding volume was 239 ml in the corticosteroid group and 203 ml in control group. There was no significant difference between the groups (p = 0.495). Surgical field quality scores were higher in the corticosteroid group than in the control group, but the difference was not significant (p = 0.36). There was no statistically significant relationship between the bleeding volume and Kennedy Osteitis Scores in corticosteroid group (r =0.225, p=0.186) and control group (r=0.084, p=0.663). Conclusion: Our findings suggest that using oral corticosteroids, which have rare but serious side effects, is not necessary in the preoperative period. Furthermore, we found that the radiological osteitis score was not a suitable marker for predicting intraoperative bleeding volumes. C1 [Gunel, C.; Basak, H. S.] Adnan Menderes Univ, Med Sch Hosp, Dept Otolaryngol Head & Neck Surg, Aydin, Turkey. [Bleier, B. S.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol Head & Neck Surg, Boston, MA USA. RP Gunel, C (reprint author), Adnan Menderes Univ, Tip Fak, Hastanesi KBB AD, TR-09100 Aydin, Turkey. EM drgunel@hotmail.com NR 25 TC 2 Z9 2 U1 0 U2 1 PU ROYAL BELGIAN SOC EAR, NOSE, THROAT, HEAD & NECK SURGERY PI LEUVEN PA PO BOX 1248, LEUVEN, 00000, BELGIUM SN 0001-6497 J9 B-ENT JI B-ENT PY 2015 VL 11 IS 2 BP 123 EP 128 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA CQ2HV UT WOS:000360421600007 PM 26563012 ER PT J AU Chhatwal, J AF Chhatwal, Jagpreet TI Direct-acting antivirals for hepatitis C treatment: effectiveness versus cost-effectiveness SO FUTURE VIROLOGY LA English DT Editorial Material DE antivirals; cost-effectiveness; direct-acting antivirals; hepatitis C; HCV ID GENOTYPE 1 INFECTION; UNITED-STATES; VIRUS-INFECTION; SOFOSBUVIR; LEDIPASVIR; THERAPY; BOCEPREVIR; REGIMENS; BURDEN C1 [Chhatwal, Jagpreet] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Chhatwal, Jagpreet] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Chhatwal, J (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. EM jagchhatwal@mgh.harvard.edu NR 24 TC 0 Z9 0 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0794 EI 1746-0808 J9 FUTURE VIROL JI Future Virol. PY 2015 VL 10 IS 8 BP 929 EP 932 DI 10.2217/FVL.15.68 PG 4 WC Virology SC Virology GA CP9NT UT WOS:000360221900002 ER PT J AU Ennis, KY Chen, MH Smith, GC D'Amico, AV Zhang, YY Quinn, SA Ryemon, SN Goltz, D Harrison, LB Ennis, RD AF Ennis, Kevin Y. Chen, Ming-Hui Smith, Glenna C. D'Amico, Anthony V. Zhang, Yuanye Quinn, S. Aidan Ryemon, Shannon N. Goltz, Daniel Harrison, Louis B. Ennis, Ronald D. TI The Impact of Economic Recession on the Incidence and Treatment of Cancer SO JOURNAL OF CANCER LA English DT Article DE economic recessions; cancer; treatment ID UNEMPLOYMENT; MORTALITY; HEALTH AB Purpose: The impact of economic recessions on the incidence and treatment of cancer is unknown. We test the hypothesis that cancer incidence and treatment rates decrease during a recession, and that this relationship is more pronounced in cancers that present with mild, more easily ignored symptoms. Methods and Materials: Data on incidence and treatment for all cancers, and breast and pancreatic cancers specifically, from 1973-2008, were collected using Surveillance Epidemiology and End Results (SEER). The data was adjusted for race, income, and education. Unemployment rate was used as the measure of economic recession. Data was log-transformed, and multivariate linear mixed regression was used. Results: Adjusting for socioeconomic factors, the data revealed a significant inverse correlation between unemployment and rates of cancer incidence and treatment. Every 1% increase in unemployment was associated with a 2.2% (95% CI: 1.6-2.8%, p<0.001) reduction in cancer incidence, a 2.0% (1.2-2.8%, p=0.0157) decrease in surgery, and a 9.1% (8.2-10.0% p<0.001) decrease in radiation therapy (RT). Breast cancer incidence and treatment had a dramatic inverse relationship 7.2% (6.3-8.1%), 6.7% (5.7-7.6%), and 19.0% (18.1-19.8%), respectively (p<0.001 for all). The decrease in incidence was only significant for in situ and localized tumors, but not in regional or distant breast cancer. Compared to breast cancer, pancreatic cancer had a weaker relationship between unemployment and incidence: 2.6% (1.8-3.3%, p=0.0005), surgery: 2.4% (2.0-2.7%, p<0.001), and RT: 1.9% (1.5-2.2% p<0.001). Conclusions: Increasing unemployment rates are associated with a decrease in the incidence and treatment of all cancers. This effect is exaggerated in breast cancer, where symptoms can more easily be ignored and where there are widely used screening tests relative to pancreatic cancer. C1 [Ennis, Kevin Y.; Smith, Glenna C.; Ryemon, Shannon N.; Goltz, Daniel; Ennis, Ronald D.] Mt Sinai Roosevelt Hosp, New York, NY 10019 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT USA. [D'Amico, Anthony V.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp, Cambridge, MA 02138 USA. [Zhang, Yuanye] Novartis Inst BioMed Res, Cambridge, MA USA. [Quinn, S. Aidan] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10027 USA. [Harrison, Louis B.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. RP Ennis, RD (reprint author), Mt Sinai Roosevelt Hosp, Radiat Oncol, 1000 Tenth Ave, New York, NY 10019 USA. EM REnnis@chpnet.org NR 11 TC 4 Z9 4 U1 0 U2 0 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1837-9664 J9 J CANCER JI J. Cancer PY 2015 VL 6 IS 8 BP 727 EP 733 DI 10.7150/jca.11886 PG 7 WC Oncology SC Oncology GA CQ0PG UT WOS:000360298200006 PM 26185534 ER PT J AU Yetisen, AK Volpatti, LR Coskun, AF Cho, S Kamrani, E Butt, H Khademhosseini, A Yun, SH AF Yetisen, Ali K. Volpatti, Lisa R. Coskun, Ahmet F. Cho, Sangyeon Kamrani, Ehsan Butt, Haider Khademhosseini, Ali Yun, Seok Hyun TI Entrepreneurship SO LAB ON A CHIP LA English DT Review ID UNIVERSITY INTELLECTUAL PROPERTY; INNOVATION RESEARCH-PROGRAM; MEDIUM-SIZED ENTERPRISES; RESEARCH-AND-DEVELOPMENT; BAYH-DOLE ACT; BIOTECHNOLOGY INDUSTRY; TECHNOLOGY-TRANSFER; START-UPS; COMMERCIALIZATION STRATEGIES; MICROFLUIDIC DEVICES AB High-tech businesses are the driving force behind global knowledge-based economies. Academic institutions have positioned themselves to serve the high-tech industry through consulting, licensing, and university spinoffs. The awareness of commercialization strategies and building an entrepreneurial culture can help academics to efficiently transfer their inventions to the market to achieve the maximum value. Here, the concept of high-tech entrepreneurship is discussed from lab to market in technology-intensive sectors such as nanotechnology, photonics, and biotechnology, specifically in the context of lab-on-a-chip devices. This article provides strategies for choosing a commercialization approach, financing a startup, marketing a product, and planning an exit. Common reasons for startup company failures are discussed and guidelines to overcome these challenges are suggested. The discussion is supplemented with case studies of successful and failed companies. Identifying a market need, assembling a motivated management team, managing resources, and obtaining experienced mentors lead to a successful exit. C1 [Yetisen, Ali K.; Cho, Sangyeon; Kamrani, Ehsan; Yun, Seok Hyun] Harvard Univ, Sch Med, Cambridge, MA 02139 USA. [Yetisen, Ali K.; Cho, Sangyeon; Kamrani, Ehsan; Yun, Seok Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Cambridge, MA 02139 USA. [Volpatti, Lisa R.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Coskun, Ahmet F.] CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA. [Cho, Sangyeon; Khademhosseini, Ali; Yun, Seok Hyun] MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Butt, Haider] Univ Birmingham, Sch Mech Engn, Birmingham B15 2TT, W Midlands, England. [Khademhosseini, Ali] Harvard Univ, Sch Med, Brigham Womens Hosp, Biomat Innovat Res Ctr,Div Biomed Engn, Cambridge, MA 02139 USA. [Khademhosseini, Ali] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Khademhosseini, Ali] King Abdulaziz Univ, Dept Phys, Jeddah 21413, Saudi Arabia. RP Yetisen, AK (reprint author), Harvard Univ, Sch Med, 65 Landsdowne St, Cambridge, MA 02139 USA. EM ayetisen@mgh.harvard.edu; syun@mgh.harvard.edu OI Khademhosseini, Ali/0000-0001-6322-8852; Butt, Haider/0000-0003-2434-9525 NR 153 TC 5 Z9 5 U1 14 U2 71 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 EI 1473-0189 J9 LAB CHIP JI Lab Chip PY 2015 VL 15 IS 18 BP 3638 EP 3660 DI 10.1039/c5lc00577a PG 23 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA CP8AY UT WOS:000360114300003 PM 26245815 ER PT J AU Yin, R Agrawal, T Khan, U Gupta, GK Rai, V Huang, YY Hamblin, MR AF Yin, Rui Agrawal, Tanupriya Khan, Usman Gupta, Gaurav K. Rai, Vikrant Huang, Ying-Ying Hamblin, Michael R. TI Antimicrobial photodynamic inactivation in nanomedicine: small light strides against bad bugs SO NANOMEDICINE LA English DT Review DE bacteria; carbon nanomaterials; fungi; liposomes; photodynamic therapy; photoinactivation; photosensitizer; titania photocatalysis; upconversion ID GRAM-NEGATIVE BACTERIA; RESISTANT STAPHYLOCOCCUS-AUREUS; WALLED CARBON NANOTUBES; PORPHYRIN-CELLULOSE NANOCRYSTALS; TITANIUM-DIOXIDE PHOTOCATALYST; GRAPHENE QUANTUM DOTS; ORGANIC SOLAR-CELLS; HEPATITIS-B-VIRUS; ESCHERICHIA-COLI; SILVER NANOPARTICLES AB The relentless advance of drug-resistance among pathogenic microbes, mandates a search for alternative approaches that will not cause resistance. Photodynamic inactivation (PDI) involves the combination of nontoxic dyes with harmless visible light to produce reactive oxygen species that can selectively kill microbial cells. PDI can be broad-spectrum in nature and can also destroy microbial cells in biofilms. Many different kinds of nanoparticles have been studied to potentiate antimicrobial PDI by improving photosensitizer solubility, photochemistry, photophysics and targeting. This review will cover photocatalytic disinfection with titania nanoparticles, carbon nanomaterials (fullerenes, carbon nanotubes and graphene), liposomes and polymeric nanoparticles. Natural polymers (chitosan and cellulose), gold and silver plasmonic nanoparticles, mesoporous silica, magnetic and upconverting nanoparticles have all been used for PDI. C1 [Yin, Rui] Third Mil Med Univ, Southwest Hosp, Dept Dermatol, Chongqing 400038, Peoples R China. [Yin, Rui; Agrawal, Tanupriya; Khan, Usman; Gupta, Gaurav K.; Huang, Ying-Ying; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Yin, Rui; Agrawal, Tanupriya; Khan, Usman; Gupta, Gaurav K.; Huang, Ying-Ying; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Rai, Vikrant] Albert Einstein Coll Med, Dept Med, Div Cardiol, Wilf Family Cardiovasc Res Inst, Bronx, NY 10461 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 Rai, Vikrant/0000-0001-6286-2341 FU NIAID NIH HHS [R01 AI050875] NR 242 TC 6 Z9 6 U1 13 U2 82 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 EI 1748-6963 J9 NANOMEDICINE-UK JI Nanomedicine PY 2015 VL 10 IS 15 BP 2379 EP 2404 DI 10.2217/NNM.15.67 PG 26 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA CP9NZ UT WOS:000360222600008 PM 26305189 ER PT J AU Lai, TH Protsenko, E Cheng, YC Loggia, ML Coppola, G Chen, WT AF Lai, Tzu-Hsien Protsenko, Ekaterina Cheng, Yu-Chen Loggia, Marco L. Coppola, Gianluca Chen, Wei-Ta TI Neural Plasticity in Common Forms of Chronic Headaches SO NEURAL PLASTICITY LA English DT Review ID MEDICATION-OVERUSE HEADACHE; MAGNETIC-RESONANCE-SPECTROSCOPY; TENSION-TYPE HEADACHE; LOW-BACK-PAIN; POSITRON-EMISSION-TOMOGRAPHY; EPISODIC CLUSTER HEADACHE; VOXEL-BASED MORPHOMETRY; BRAIN-STEM ACTIVATION; GREY-MATTER CHANGES; NOXIOUS INHIBITORY CONTROLS AB Headaches are universal experiences and among the most common disorders. While headache may be physiological in the acute setting, it can become a pathological and persistent condition. The mechanisms underlying the transition from episodic to chronic pain have been the subject of intense study. Using physiological and imaging methods, researchers have identified a number of different forms of neural plasticity associated with migraine and other headaches, including peripheral and central sensitization, and alterations in the endogenous mechanisms of pain modulation. While these changes have been proposed to contribute to headache and pain chronification, some findings are likely the results of repetitive noxious stimulation, such as atrophy of brain areas involved in pain perception and modulation. In this review, we provide a narrative overview of recent advances on the neuroimaging, electrophysiological and genetic aspects of neural plasticity associated with the most common forms of chronic headaches, including migraine, cluster headache, tension-type headache, and medication overuse headache. C1 [Lai, Tzu-Hsien; Cheng, Yu-Chen; Chen, Wei-Ta] Natl Yang Ming Univ, Sch Med, Dept Neurol, Taipei 112, Taiwan. [Lai, Tzu-Hsien; Cheng, Yu-Chen] Far Eastern Mem Hosp, Dept Internal Med, Sect Neurol, New Taipei City 220, Taiwan. [Protsenko, Ekaterina; Loggia, Marco L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. [Coppola, Gianluca] GB Bietti Fdn IRCCS, Dept Neurophysiol Vis & Neurophthalmol, I-00198 Rome, Italy. [Chen, Wei-Ta] Natl Yang Ming Univ, Sch Med, Inst Brain Sci, Taipei 112, Taiwan. [Chen, Wei-Ta] Taipei Vet Gen Hosp, Neurol Inst, Taipei 112, Taiwan. RP Chen, WT (reprint author), Natl Yang Ming Univ, Sch Med, Dept Neurol, Taipei 112, Taiwan. EM wtchen@vghtpe.gov.tw FU Italian Ministry of Health and Fondazione Roma [W81XWH-14-1-0543, R21 NS087472]; Ministry of Science and Technology, Taiwan [MOST 103-2628-B-075-001-MY3, MOST 103-2314-B-418-009]; Taipei Veterans General Hospital [VGHUST104-G7-1-3, V104C-115]; Far Eastern Memorial Hospital [FEMH-2015-C-017] FX This project was supported by the Italian Ministry of Health and Fondazione Roma (Gianluca Coppola), W81XWH-14-1-0543 (Marco L. Loggia), R21 NS087472 (Marco L. Loggia), Ministry of Science and Technology, Taiwan (MOST 103-2628-B-075-001-MY3 to Wei-Ta Chen and MOST 103-2314-B-418-009 to Tzu-Hsien Lai), Taipei Veterans General Hospital (VGHUST104-G7-1-3 and V104C-115 to Wei-Ta Chen), and Far Eastern Memorial Hospital (FEMH-2015-C-017 to Tzu-Hsien Lai). NR 181 TC 4 Z9 4 U1 0 U2 9 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 2090-5904 EI 1687-5443 J9 NEURAL PLAST JI Neural. Plast. PY 2015 AR 205985 DI 10.1155/2015/205985 PG 14 WC Neurosciences SC Neurosciences & Neurology GA CQ3JQ UT WOS:000360498600001 ER PT J AU Paganoni, S Karam, C Joyce, N Bedlack, R Carter, GT AF Paganoni, Sabrina Karam, Chafic Joyce, Nanette Bedlack, Richard Carter, Gregory T. TI Comprehensive rehabilitative care across the spectrum of amyotrophic lateral sclerosis SO NEUROREHABILITATION LA English DT Review DE Amyotrophic lateral sclerosis; rehabilitation; quality of life; function; supportive care; palliative care; braces; equipment; assistive device ID QUALITY-OF-LIFE; MOTOR-NEURON DISEASE; BRAIN-COMPUTER-INTERFACE; PRACTICE PARAMETER UPDATE; LOCKED-IN SYNDROME; ALS PATIENTS; INVASIVE VENTILATION; PSEUDOBULBAR AFFECT; AMERICAN ACADEMY; PILOT TRIAL AB BACKGROUND: Amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease) is a neurodegenerative disease that results in progressive muscle weakness and wasting. There is no known cure and the disease is uniformly fatal. PURPOSE: This review discusses current concepts in ALS care, from breaking the diagnosis to end-of-life care. People with ALS have several multidisciplinary needs due to a complex and dynamic disease process. They benefit from rehabilitation interventions that are individualized and have the goal of optimizing independence, function, and safety. These strategies also help minimize symptomatic burden and maximize quality of life. CONCLUSION: Patient-centered, multidisciplinary care has a significant impact on the life of people with ALS and is the current standard of care for this patient population. C1 [Paganoni, Sabrina] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Paganoni, Sabrina] Massachusetts Gen Hosp, Spaulding Rehabil Hosp, Boston, MA 02114 USA. [Paganoni, Sabrina] Boston VA Healthcare Syst, Boston, MA USA. [Karam, Chafic] Univ N Carolina, Sch Med, Dept Neurol, Chapel Hill, NC 27599 USA. [Joyce, Nanette] Univ Calif Davis, Sch Med, Neuromuscular Sect, Dept Phys Med & Rehabil, Sacramento, CA 95817 USA. [Bedlack, Richard] Duke Univ, Sch Med, Durham, NC USA. [Bedlack, Richard] Duke Univ, Durham Vet Affairs Med Ctr, Durham, NC USA. [Carter, Gregory T.] St Lukes Rehabil Inst, Dept Phys Med & Rehabil, Spokane, WA USA. RP Paganoni, S (reprint author), Massachusetts Gen Hosp, Neurol Clin Res Inst NCRI, 165 Cambridge St,Suite 600, Boston, MA 02114 USA. EM spaganoni@mgh.harvard.edu FU NICHD NIH HHS [K12 HD001097] NR 144 TC 0 Z9 0 U1 5 U2 19 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1053-8135 EI 1878-6448 J9 NEUROREHABILITATION JI Neurorehabilitation PY 2015 VL 37 IS 1 BP 53 EP 68 DI 10.3233/NRE-151240 PG 16 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA CQ2ET UT WOS:000360412900006 PM 26409693 ER PT J AU Chen, YC Duda, DG AF Chen, Yunching Duda, Dan G. TI Targeting immunosuppression after standard sorafenib treatment to facilitate immune checkpoint blockade in hepatocellular carcinoma - an auto-commentary on clinical potential and future development SO ONCOIMMUNOLOGY LA English DT Editorial Material DE combination therapy; CXCR4 hepatocellular carcinoma; immune checkpoint blockade; immunosuppression; PD-1 ID TUMOR MICROENVIRONMENT; CANCER-IMMUNOTHERAPY; MICE AB Immunotherapy has shown great promise to transform solid cancer treatment. The challenge is to optimally incorporate novel immunotherapeutics, such as immune checkpoint blockers, with standard therapies. This is well exemplified by multimodal therapies recently developed for liver cancer in which immunomodulation using CXCR4 inhibition prevented immunosuppression and enhanced sorafenib and anti-PD-1 therapeutic outcome. C1 [Chen, Yunching] Natl Tsing Hua Univ, Inst Biomed Engn, Hsinchu, Taiwan. [Chen, Yunching; Duda, Dan G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Labs Tumor Biol, Boston, MA 02114 USA. [Chen, Yunching; Duda, Dan G.] Harvard Univ, Sch Med, Boston, MA USA. RP Chen, YC (reprint author), Natl Tsing Hua Univ, Inst Biomed Engn, Hsinchu, Taiwan. EM yunching@mx.nthu.edu.tw; gduda@partners.org NR 10 TC 1 Z9 1 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PY 2015 VL 4 IS 10 AR e1029703 DI 10.1080/2162402X.2015.1029703 PG 3 WC Oncology; Immunology SC Oncology; Immunology GA CP9UT UT WOS:000360241200007 ER PT J AU Tsao, CY Sabbatino, F Cheung, NKV Hsu, JCF Villani, V Wang, XH Ferrone, S AF Tsao, Chun-Yen Sabbatino, Francesco Cheung, Nai-Kong V. Hsu, Jeff Chi-Feng Villani, Vincenzo Wang, Xinhui Ferrone, Soldano TI Anti-proliferative and pro-apoptotic activity of GD2 ganglioside-specific monoclonal antibody 3F8 in human melanoma cells SO ONCOIMMUNOLOGY LA English DT Article DE antibody; apoptosis; GD2 ganglioside; internalization; melanoma ID STAGE 4 NEUROBLASTOMA; HUMAN-TUMOR CELLS; CELLULAR CYTOTOXICITY; SIGNAL-TRANSDUCTION; MALIGNANT-MELANOMA; NEURO-BLASTOMA; CYTO-TOXICITY; MURINE IGG3; PHASE-II; EXPRESSION AB The beneficial clinical effects of immunotherapy with GD2-specific monoclonal antibodies (mAbs) in melanoma and neuroblastoma patients have stimulated interest in characterizing the mechanisms underlying their antitumor effects. Previous studies have shown that GD2-specific mAbs mediate complement-and cell-dependent cytotoxicity and induce caspase-dependent apoptosis of tumor cells. In this study, we showed that GD2-specific mAb 3F8, which is undergoing clinical evaluation, inhibited the in vitro growth and induced apoptosis of melanoma cells. This effect was dose-and time-dependent, mediated by the interaction of mAb 3F8 combining site with GD2 ganglioside, associated with GD2 expression level on the cell surface, mAb internalization and increase of GD2 containing endosomes triggered by mAb 3F8. The induction of apoptosis by mAb 3F8 was mediated by caspase 3-, 7-, and 8-dependent pathways, downregulation of the anti-apoptotic molecules survivin and cytochrome c, and caspase 9 independent-AIF release from mitochondria. In addition, analyses of signaling pathway components demonstrated that mAb 3F8 strongly inhibited AKT and FAK activation and increased cleaved PARP expression. These results indicated that multiple mechanisms played a role in the antitumor activity of mAb 3F8 in melanoma cells. This information should provide a mechanistic basis for the optimization of the rational design of immunotherapeutic strategies in the mAb-based treatment of GD2 positive tumors. C1 [Tsao, Chun-Yen; Sabbatino, Francesco; Hsu, Jeff Chi-Feng; Villani, Vincenzo; Wang, Xinhui; Ferrone, Soldano] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Cheung, Nai-Kong V.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. RP Ferrone, S (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM sferrone@partners.org RI Sabbatino, Francesco/F-4992-2014 OI Sabbatino, Francesco/0000-0001-6431-8278 FU PHS - National Cancer Institute [RO1CA138188, P50CA121973]; Fondazione Umberto Veronesi Post-Doctoral Fellowship - Fondazione Umberto Veronesi; Centro per la Comunicazione e la Ricerca of the Collegio Ghislieri of Pavia FX This work was supported by PHS grants RO1CA138188 and P50CA121973 awarded by the National Cancer Institute (SF), by Fondazione Umberto Veronesi Post-Doctoral Fellowship awarded by the Fondazione Umberto Veronesi (FS) and by Research Fellowship awarded by the Centro per la Comunicazione e la Ricerca of the Collegio Ghislieri of Pavia (VV). NR 48 TC 3 Z9 3 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2162-402X J9 ONCOIMMUNOLOGY JI OncoImmunology PY 2015 VL 4 IS 8 AR e1023975 DI 10.1080/2162402X.2015.1023975 PG 10 WC Oncology; Immunology SC Oncology; Immunology GA CP9UD UT WOS:000360239300019 PM 26405581 ER PT J AU Normoyle, KP Kim, M Farahvar, A Llano, D Jackson, K Wang, H AF Normoyle, Kieran P. Kim, Miri Farahvar, Arash Llano, Daniel Jackson, Kevin Wang, Huan TI THE EMERGING NEUROPROTECTIVE ROLE OF MITOCHONDRIAL UNCOUPLING PROTEIN-2 IN TRAUMATIC BRAIN INJURY SO TRANSLATIONAL NEUROSCIENCE LA English DT Article DE Neuronal injury; Mitochondria; Traumatic brain injury; Ischemia; Neuronal cell death ID PREVENTS NEURONAL DEATH; PARKINSONS-DISEASE; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; CARDIAC-ARREST; CELL-DEATH; TEMPERATURE MANAGEMENT; MILD HYPOTHERMIA; RAT-BRAIN; BROWN FAT AB Traumatic brain injury (TBI) is a multifaceted disease with intrinsically complex heterogeneity and remains a significant clinical challenge to manage. TBI model systems have demonstrated many mechanisms that contribute to brain parenchymal cell death, including glutamate and calcium toxicity, oxidative stress, inflammation, and mitochondrial dysfunction. Mitochondria are critically regulated by uncoupling proteins (UCP), which allow protons to leak back into the matrix and thus reduce the mitochondrial membrane potential by dissipating the proton motive force. This uncoupling of oxidative phosphorylation from adenosine triphosphate (ATP) synthesis is potentially critical for protection against cellular injury as a result of TBI and stroke. A greater understanding of the underlying mechanism or mechanisms by which uncoupling protein-2 (UCP2) functions to maintain or optimize mitochondrial function, and the conditions which precipitate the failure of these mechanisms, would inform future research and treatment strategies. We posit that UCP2-mediated function underlies the physiological response to neuronal stress associated with traumatic and ischemic injury and that clinical development of UCP2-targeted treatment would significantly impact these patient populations. With a focus on clinical relevance in TBI, we synthesize current knowledge concerning UCP2 and its potential neuroprotective role and apply this body of knowledge to current and potential treatment modalities. C1 [Normoyle, Kieran P.; Llano, Daniel] Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA. [Normoyle, Kieran P.; Kim, Miri] Univ Illinois, Coll Med, Urbana, IL 61801 USA. [Normoyle, Kieran P.] Massachusetts Gen Hosp, Dept Child Neurol, Boston, MA 02114 USA. [Kim, Miri] Univ Illinois, Dept Cell & Dev Biol, Urbana, IL 61801 USA. [Farahvar, Arash] Carle Fdn Hosp, Dept Neurosurg, Urbana, IL USA. [Llano, Daniel; Wang, Huan] Carle Fdn Hosp, Dept Neurol, Urbana, IL 61801 USA. [Llano, Daniel; Jackson, Kevin] Univ Illinois, Beckman Inst, Urbana, IL 61801 USA. [Jackson, Kevin; Wang, Huan] Univ Illinois, Beckman Inst, TNL, Urbana, IL 61801 USA. RP Wang, H (reprint author), Carle Fdn Hosp, Dept Neurol, Urbana, IL 61801 USA. EM huanwang@illinois.edu NR 107 TC 1 Z9 1 U1 0 U2 1 PU DE GRUYTER OPEN LTD PI WARSAW PA BOGUMILA ZUGA 32A ST, 01-811 WARSAW, POLAND SN 2081-3856 EI 2081-6936 J9 TRANSL NEUROSCI JI Transl. Neurosci. PD JAN PY 2015 VL 6 IS 1 BP 179 EP 186 DI 10.1515/tnsci-2015-0019 PG 8 WC Neurosciences SC Neurosciences & Neurology GA CQ6GJ UT WOS:000360702200012 PM 28123803 ER PT J AU Vodicka, P Mo, S Tousley, A Green, KM Sapp, E Iuliano, M Sadri-Vakili, G Shaffer, SA Aronin, N DiFiglia, M Kegel-Gleason, KB AF Vodicka, Petr Mo, Shunyan Tousley, Adelaide Green, Karin M. Sapp, Ellen Iuliano, Maria Sadri-Vakili, Ghazaleh Shaffer, Scott A. Aronin, Neil DiFiglia, Marian Kegel-Gleason, Kimberly B. TI Mass Spectrometry Analysis of Wild-Type and Knock-in Q140/Q140 Huntington's Disease Mouse Brains Reveals Changes in Glycerophospholipids Including Alterations in Phosphatidic Acid and Lyso-Phosphatidic Acid SO JOURNAL OF HUNTINGTONS DISEASE LA English DT Article DE Huntington's disease; Huntingtin; glycerophospholipid; mass spectrometry; phosphatidic acid; acyl transferase; lipidomics; CtBP; LPAAT; phospholipase; LPA ID TERMINAL BINDING-PROTEIN; PPAR-GAMMA AGONIST; GENE-EXPRESSION; LYSOPHOSPHOLIPASE-D; EARLY MOTOR; POLYGLUTAMINE EXPANSION; MUTANT HUNTINGTIN; OXIDATIVE STRESS; GLOBUS PALLIDUS; FATTY-ACIDS AB Background: Huntington's disease (HD) is a neurodegenerative disease caused by a CAG expansion in the HD gene, which encodes the protein Huntingtin. Huntingtin associates with membranes and can interact directly with glycerophospholipids in membranes. Objective: We analyzed glycerophospholipid profiles from brains of 11 month old wild-type (WT) and Q140/Q140 HD knock-in mice to assess potential changes in glycerophospholipid metabolism. Methods: Polar lipids from cerebellum, cortex, and striatum were extracted and analyzed by liquid chromatography and negative ion electrospray tandem mass spectrometry analysis (LC-MS/MS). Gene products involved in polar lipid metabolism were studied using western blotting, immuno-electron microscopy and qPCR. Results: Significant changes in numerous species of glycerophosphate (phosphatidic acid, PA) were found in striatum, cerebellum and cortex from Q140/Q140 HD mice compared to WT mice at 11 months. Changes in specific species could also be detected for other glycerophospholipids. Increases in species of lyso-PA (LPA) were measured in striatum of Q140/Q140 HD mice compared to WT. Protein levels for c-terminal binding protein 1 (CtBP1), a regulator of PA biosynthesis, were reduced in striatal synaptosomes from HD mice compared to wild-type at 6 and 12 months. Immunoreactivity for CtBP1 was detected on membranes of synaptic vesicles in striatal axon terminals in the globus pallidus. Conclusions: These novel results identify a potential site of molecular pathology caused by mutant Huntingtin that may impart early changes in HD. C1 [Vodicka, Petr; Tousley, Adelaide; Sapp, Ellen; Iuliano, Maria; Sadri-Vakili, Ghazaleh; DiFiglia, Marian; Kegel-Gleason, Kimberly B.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Mo, Shunyan; Green, Karin M.; Shaffer, Scott A.] UMASS Med Sch, Prote & Mass Spectrometry Facil, Worcester, MA USA. [Mo, Shunyan; Green, Karin M.; Shaffer, Scott A.] UMASS Med Sch, Dept Biochem & Mol Pharmacol, Worcester, MA USA. [Aronin, Neil] UMASS Med Sch, Dept Med, Worcester, MA USA. [Aronin, Neil] UMASS Med Sch, Dept Cell & Dev Biol, Worcester, MA USA. RP Kegel-Gleason, KB (reprint author), Massachusetts Gen Hosp, Dept Neurol, Mass Gen Inst Neurodegenerat MIND, 114 16th St,Room 2001, Charlestown, MA 02129 USA. EM kkegel@partners.org RI Vodicka, Petr/C-3845-2009 OI Vodicka, Petr/0000-0002-6605-9158 FU NCRR NIH HHS [1S10RR023594S10]; NINDS NIH HHS [NS 038194-13] NR 72 TC 1 Z9 1 U1 1 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1879-6397 EI 1879-6400 J9 J HUNTINGTONS DIS JI J. Huntingtons Dis. PY 2015 VL 4 IS 2 BP 187 EP 201 DI 10.3233/JHD-150149 PG 15 WC Neurosciences SC Neurosciences & Neurology GA CQ2EF UT WOS:000360411500008 PM 26397899 ER PT J AU Vergani, A Gatti, F Lee, KM D'Addio, F Tezza, S Chin, M Bassi, R Tian, Z Wu, EX Maffi, P Ben Nasr, M Kim, JI Secchi, A Markmann, JF Rothstein, DM Turka, LA Sayegh, MH Fiorina, P AF Vergani, Andrea Gatti, Francesca Lee, Kang M. D'Addio, Francesca Tezza, Sara Chin, Melissa Bassi, Roberto Tian, Ze Wu, Erxi Maffi, Paola Ben Nasr, Moufida Kim, James I. Secchi, Antonio Markmann, James F. Rothstein, David M. Turka, Laurence A. Sayegh, Mohamed H. Fiorina, Paolo TI TIM4 Regulates the Anti-Islet Th2 Alloimmune Response SO CELL TRANSPLANTATION LA English DT Article DE Islet transplantation; Autoimmune diabetes; Costimulatory molecules; Regulatory cells ID ISLET TRANSPLANTATION; T-CELLS; GENE FAMILY; NOD MICE; ALLOGRAFT-REJECTION; EMERGING ROLE; B-CELLS; AUTOIMMUNE; TOLERANCE; SURVIVAL AB The role of the novel costimulatory molecule TIM4 in anti-islet response is unknown. We explored TIM4 expression and targeting in Th1 (BALB/c islets into C57BL/6 mice) and Th2 (BALB/c islets into Tbet(-/-)C57BL/6 mice) models of anti-islet alloimmune response and in a model of anti-islet autoimmune response (diabetes onset in NOD mice). The targeting of TIM4, using the monoclonal antibody RMT4-53, promotes islet graft survival in a Th1 model, with 30% of the graft surviving in the long term; islet graft protection appears to be mediated by a nil to Th2 skewing of the immune response. Differently, in the Th2 model, TIM4 targeting precipitates graft rejection by further enhancing the Th2 response. The effect of anti-TIM4 treatment in preventing autoimmune diabetes was marginal with only minor Th1 to Th2 skewing. B-Cell depletion abolished the effect of TIM4 targeting. TIM4 is expressed on human B-cells and is upregulated in diabetic and islet-transplanted patients. Our data suggest a model in which TIM4 targeting promotes Th2 response over Th1 via B-cells. The targeting of TIM4 could become a component of an immunoregulatory protocol in clinical islet transplantation, aiming at redirecting the immune system toward a Th2 response. C1 [Vergani, Andrea; Gatti, Francesca; D'Addio, Francesca; Tezza, Sara; Chin, Melissa; Bassi, Roberto; Ben Nasr, Moufida; Sayegh, Mohamed H.; Fiorina, Paolo] Harvard Univ, Sch Med, Boston Childrens Hosp, Transplantat Res Ctr,Div Nephrol, Boston, MA 02115 USA. [Vergani, Andrea; Gatti, Francesca; D'Addio, Francesca; Tezza, Sara; Chin, Melissa; Bassi, Roberto; Ben Nasr, Moufida; Sayegh, Mohamed H.; Fiorina, Paolo] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Vergani, Andrea; D'Addio, Francesca; Maffi, Paola; Secchi, Antonio; Fiorina, Paolo] Univ Milan, Osped San Raffaele, Transplant Med, I-20127 Milan, Italy. [Gatti, Francesca] Univ Salento, Lecce, Italy. [Lee, Kang M.; Kim, James I.; Markmann, James F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplant Surg, Boston, MA 02115 USA. [Tian, Ze] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wu, Erxi] N Dakota State Univ, Dept Pharmaceut Sci, Fargo, ND 58105 USA. [Secchi, Antonio] Univ Vita Salute San Raffaele, Milan, Italy. [Rothstein, David M.] Univ Pittsburgh, Dept Immunol, Pittsburgh, PA USA. [Turka, Laurence A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Ctr Transplantat Sci, Boston, MA 02115 USA. RP Fiorina, P (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Div Nephrol, Enders Bldg,5th Floor,Room EN530, Boston, MA 02115 USA. EM paolo.fiorina@childrens.harvard.edu RI D'Addio, Francesca/F-3417-2017 OI D'Addio, Francesca/0000-0002-0345-0694 FU JDRF Career Development Award; ASN Career Development Award; ADA Mentor-based Fellowship grant; Translational Research Program (TRP) grant from Boston Children's Hospital; Harvard Stem Cell Institute grant ("Diabetes Program") [DP-0123-12-00]; Italian Ministry of Health grant [RF-2010-2303119, RF-FSR-2008-1213704]; NIH-Research Training grant [T32DK007726-28]; AMD-SID Pasquale di Coste Scolarship; Italian Scientists and Scholars of North America Foundation (ISSNAF)-Fondazione Marche Fellowship; AST Genentech Clinical Science Fellowship [R01 AI-037691] FX Paolo Fiorina is the recipient of a JDRF Career Development Award, an ASN Career Development Award, and an ADA Mentor-based Fellowship grant. P.F. is also supported by a Translational Research Program (TRP) grant from Boston Children's Hospital; Harvard Stem Cell Institute grant ("Diabetes Program" DP-0123-12-00); Italian Ministry of Health grant RF-2010-2303119. P.F. and Andrea Vergani are supported by an Italian Ministry of Health grant: ("Staminali" RF-FSR-2008-1213704). A.V. has been supported by an NIH-Research Training grant to Boston Children's Hospital in Pediatric Nephrology (T32DK007726-28). A.V. is supported by the "AMD-SID Pasquale di Coste Scolarship." Francesca D'Addio is a recipient of Italian Scientists and Scholars of North America Foundation (ISSNAF)-Fondazione Marche Fellowship. Roberto Bassi is supported by an ADA Mentor-based Fellowship grant to P.F. and by an AST Genentech Clinical Science Fellowship Laurence A. Turka is funded by R01 AI-037691. A.V. conducted this study as partial fulfillment of his Ph.D. in molecular medicine, San Raffaele University, Milan, Italy. The authors declare no conflicts of interest. NR 46 TC 1 Z9 1 U1 0 U2 0 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 2015 VL 24 IS 8 BP 1599 EP 1614 DI 10.3727/096368914X678571 PG 16 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA CP4UU UT WOS:000359878900014 PM 24612609 ER PT J AU Zhang, XL Shi, HJ Wang, JP Tang, HS Cui, SZ AF Zhang, Xiang-Liang Shi, Hui-Juan Wang, Ji-Ping Tang, Hong-Sheng Cui, Shu-Zhong TI miR-218 inhibits multidrug resistance (MDR) of gastric cancer cells by targeting Hedgehog/smoothened SO INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY LA English DT Article DE Gastric cancer; hedgehog; hsa-miR-218; multi-drug resistance; SMO ID HEDGEHOG SIGNAL-TRANSDUCTION; PATHWAY INHIBITORS; CARCINOMA CELLS; DOWN-REGULATION; IN-VITRO; TRANSPORTERS; PHOSPHORYLATION; MICRORNA-218; OXALIPLATIN; INVASION AB Multidrug resistance (MDR) is the main obstacle to successful chemotherapy for patients with gastric cancer. The microRNA miR-218 influences various pathobiological processes in gastric cancer, and its down-regulation in this disease raises the question of whether it normally inhibits MDR. In this study we observed that two MDR gastric cancer cell lines showed lower expression of miR-218 compared with their chemosensitive parental cell line. Overexpressing miR-218 chemosensitizes gastric cancer cells, slowed efflux of adriamycin, and accelerated drug-induced apoptosis. We identified the smoothened (SMO) gene as a functional target of miR-218, and found that SMO overexpression counteracts the chemosensitizing effects of miR-218. These findings suggest that miR-218 inhibits MDR of gastric cancer cells by down-regulating SMO expression. C1 [Zhang, Xiang-Liang; Tang, Hong-Sheng; Cui, Shu-Zhong] Guangzhou Med Univ, Affiliated Canc Hosp, Dept Abdominal Surg Sect 2, Guangzhou 510095, Guangdong, Peoples R China. [Shi, Hui-Juan] Sun Yat Sen Univ, Dept Pathol, Affiliated Hosp 1, Guangzhou 510080, Guangdong, Peoples R China. [Wang, Ji-Ping] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Wang, Ji-Ping] Harvard Univ, Sch Med, Boston, MA USA. [Wang, Ji-Ping] Massachusetts Gen Hosp, Dept Surg & Pathol, Boston, MA 02114 USA. RP Cui, SZ (reprint author), Guangzhou Med Univ, Affiliated Canc Hosp, Dept Abdominal Surg Sect 2, 78 Hengzhigang Rd, Guangzhou 510095, Guangdong, Peoples R China. EM 513340728@qq.com FU Guangdong Province Natural Science Foundation [S2013010016662]; Health Bureau of Guangdong Province [A2014224, B2014196]; Science and Technology Planning Project of Guangdong Province [2013B021800284]; National Natural Science Foundation of China [81201932, 81372493] FX This work was supported by Guangdong Province Natural Science Foundation (S2013010016662), Health Bureau of Guangdong Province (A2014224 and B2014196), Science and Technology Planning Project of Guangdong Province (2013B021800284) and the National Natural Science Foundation of China (81201932 and 81372493). NR 35 TC 9 Z9 12 U1 0 U2 4 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 1936-2625 J9 INT J CLIN EXP PATHO JI Int. J. Clin. Exp. Pathol. PY 2015 VL 8 IS 6 BP 6397 EP 6406 PG 10 WC Oncology; Pathology SC Oncology; Pathology GA CO6PD UT WOS:000359277700038 PM 26261515 ER PT J AU Brenes-Salazar, JA Alshawabkeh, L Schmader, KE Hanlon, JT Forman, DE AF Brenes-Salazar, Jorge A. Alshawabkeh, Laith Schmader, Kenneth E. Hanlon, Joseph T. Forman, Daniel E. TI Clinical pharmacology relevant to older adults with cardiovascular disease SO JOURNAL OF GERIATRIC CARDIOLOGY LA English DT Editorial Material DE Metabolism; Pharmacokinetics; Pharmacodynamics; Polypharmacy ID DRUG-DRUG; ADHERENCE C1 [Brenes-Salazar, Jorge A.] Mayo Clin, Dept Med, Div Cardiovasc Dis, Rochester, MN USA. [Alshawabkeh, Laith] Univ Iowa, Dept Med, Div Cardiovasc Dis, Iowa City, IA 52242 USA. [Schmader, Kenneth E.] Duke Univ, Sch Med, Dept Med, Div Geriatr, Durham, NC 27706 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Dept Med, Geriatr Res Educ & Clin Ctr, Div Geriatr Med, Pittsburgh, PA USA. [Hanlon, Joseph T.] Univ Pittsburgh, Dept Pharm, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Hanlon, Joseph T.] Univ Pittsburgh, Dept Epidemiol, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Hanlon, Joseph T.] VA Pittsburgh Hlth Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Forman, Daniel E.] Univ Pittsburgh, VA Pittsburgh Hlth Syst, Geriatr Res Educ & Clin Ctr, Dept Med,Div Geriatr Med,Med Ctr, Pittsburgh, PA 15260 USA. [Forman, Daniel E.] Univ Pittsburgh, VA Pittsburgh Hlth Syst, Geriatr Res Educ & Clin Ctr, Div Cardiol,Med Ctr, Pittsburgh, PA USA. RP Forman, DE (reprint author), Univ Pittsburgh, VA Pittsburgh Hlth Syst, Geriatr Res Educ & Clin Ctr, Dept Med,Div Geriatr Med,Med Ctr, Pittsburgh, PA 15260 USA. EM formand@pitt.edu FU NIA NIH HHS [K07 AG033174, P30 AG024827, P30 AG028716, R01 AG037451] NR 11 TC 2 Z9 2 U1 1 U2 2 PU SCIENCE PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 1671-5411 J9 J GERIATR CARDIOL JI J. Geriatr. Cardiol. PY 2015 VL 12 IS 3 BP 192 EP 195 PG 4 WC Cardiac & Cardiovascular Systems; Geriatrics & Gerontology SC Cardiovascular System & Cardiology; Geriatrics & Gerontology GA CP6SE UT WOS:000360017600002 PM 26089839 ER PT J AU Franklin, R Zorowitz, S Corse, AK Widge, AS Deckersbach, T AF Franklin, Rachel Zorowitz, Sam Corse, Andrew K. Widge, Alik S. Deckersbach, Thilo TI Lurasidone for the treatment of bipolar depression: an evidence-based review SO NEUROPSYCHIATRIC DISEASE AND TREATMENT LA English DT Review DE lurasidone; bipolar depression; bipolar disorder; atypical antipsychotic ID DOUBLE-BLIND; I DEPRESSION; 2ND-GENERATION ANTIPSYCHOTICS; SCHIZOAFFECTIVE DISORDER; OPEN-LABEL; SCHIZOPHRENIA; EFFICACY; TOLERABILITY; 5-HT7; QUETIAPINE AB Bipolar disorder (BD) is a debilitating and difficult-to-treat psychiatric disease that presents a serious burden to patients' lives as well as health care systems around the world. The essential diagnostic criterion for BD is episodes of mania or hypomania; however, the patients report that the majority of their time is spent in a depressive phase. Current treatment options for this component of BD have yet to achieve satisfactory remission rates. Lurasidone is a drug in the benzisothiazole class approved by the US Food and Drug Administration in June 2013 for the acute treatment of bipolar depression. Its pharmacological profile features high-affinity antagonism at D-2, 5-HT2A, and 5-HT7 receptors; moderate-affinity antagonism at alpha(2C)-adrenergic receptors; low-to very low-affinity antagonism at alpha(1A)-adrenergic, alpha(2A)-adrenergic, H-1, M-1, and 5-HT2C receptors; and high-affinity partial agonism at 5-HT1A. Preliminary findings from two recent double-blinded clinical trials suggest that lurasidone is efficacious in treating bipolar I depression, with clinical effects manifesting as early as the first 2-3 weeks of treatment (as measured by the Montgomery-Asberg Depression Rating Scale and Clinical Global Impressions Scale for use in bipolar illness). Its therapeutic benefit appears to be comparable to the current US Food and Drug Administration-indicated treatments: quetiapine and olanzapine-fluoxetine, according to a measure of effect size known as number needed to treat. These studies reported relatively limited extrapyramidal and metabolic side effects as a result of treatment with lurasidone, with the most common side effect being nausea. Safety data drawn from these studies, as well as a more extensive body of schizophrenia research, indicate that in comparison with other atypical antipsychotics, treatment with lurasidone is less likely to result in metabolic side effects such as weight gain or disturbances of serum glucose or lipid levels. Lurasidone holds clinical potential as a novel, efficacious pharmacological treatment for bipolar depression. However, current data on its use for the treatment of BD are limited, and more extensive research, both longer in duration as well as independently conducted, is needed. C1 [Franklin, Rachel; Zorowitz, Sam; Corse, Andrew K.; Deckersbach, Thilo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Neurotherapeut,Dept Psychiat, Charlestown, MA 02129 USA. [Widge, Alik S.] MIT, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. RP Deckersbach, T (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Neurotherapeut,Dept Psychiat, Room 2628,Bldg 149,13th St, Charlestown, MA 02129 USA. EM tdeckersbach@partners.org NR 63 TC 7 Z9 7 U1 0 U2 10 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-2021 J9 NEUROPSYCH DIS TREAT JI Neuropsychiatr. Dis. Treat. PY 2015 VL 11 BP 2143 EP 2152 DI 10.2147/NDT.S50961 PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CP7IM UT WOS:000360060500001 PM 26316760 ER PT J AU Morries, LD Cassano, P Henderson, TA AF Morries, Larry D. Cassano, Paolo Henderson, Theodore A. TI Treatments for traumatic brain injury with emphasis on transcranial near-infrared laser phototherapy SO NEUROPSYCHIATRIC DISEASE AND TREATMENT LA English DT Review DE infrared; traumatic brain injury; TBI; transcranial infrared light therapy; transcranial laser therapy ID LOW-LEVEL LASER; HYPERBARIC-OXYGEN THERAPY; POSTTRAUMATIC-STRESS-DISORDER; TERM NEUROLOGICAL DEFICITS; POST-CONCUSSION SYNDROME; ACUTE ISCHEMIC-STROKE; POSITRON-EMISSION-TOMOGRAPHY; TRANSIENT CEREBRAL-ISCHEMIA; DEPLOYED MILITARY PERSONNEL; GINKGO-BILOBA EXTRACT AB Traumatic brain injury (TBI) is a growing health concern affecting civilians and military personnel. In this review, treatments for the chronic TBI patient are discussed, including pharmaceuticals, nutraceuticals, cognitive therapy, and hyperbaric oxygen therapy. All available literature suggests a marginal benefit with prolonged treatment courses. An emerging modality of treatment is near-infrared (NIR) light, which has benefit in animal models of stroke, spinal cord injury, optic nerve injury, and TBI, and in human trials for stroke and TBI. The extant literature is confounded by variable degrees of efficacy and a bewildering array of treatment parameters. Some data indicate that diodes emitting low-level NIR energy often have failed to demonstrate therapeutic efficacy, perhaps due to failing to deliver sufficient radiant energy to the necessary depth. As part of this review, we present a retrospective case series using high-power NIR laser phototherapy with a Class IV laser to treat TBI. We demonstrate greater clinical efficacy with higher fluence, in contrast to the bimodal model of efficacy previously proposed. In ten patients with chronic TBI (average time since injury 9.3 years) given ten treatments over the course of 2 months using a high-power NIR laser (13.2 W/0.89 cm(2) at 810 nm or 9 W/0.89 cm(2) at 810 nm and 980 nm), symptoms of headache, sleep disturbance, cognition, mood dysregulation, anxiety, and irritability improved. Symptoms were monitored by depression scales and a novel patient diary system specifically designed for this study. NIR light in the power range of 10-15 W at 810 nm and 980 nm can safely and effectively treat chronic symptoms of TBI. The clinical benefit and effects of infrared phototherapy on mitochondrial function and secondary molecular events are discussed in the context of adequate radiant energy penetration. C1 [Morries, Larry D.; Henderson, Theodore A.] Neurolaser Fdn, Lakewood, CO USA. [Cassano, Paolo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA USA. [Henderson, Theodore A.] Synapt Space, Centennial, CO 80112 USA. RP Henderson, TA (reprint author), Synapt Space, 3979 East Arapahoe Rd,Suite 200, Centennial, CO 80112 USA. EM thesynapticspace7@gmail.com FU Brain and Behavior Research Foundation; Photothera Inc FX Dr Larry D Morries is the CEO of Neuro-Laser Foundation, a nonprofit foundation. He has a private practice in Lakewood, CO. Theodore A Henderson is the president of The Synaptic Space, a medical consulting firm. He is the president of Dr Theodore Henderson, Inc., a clinical service firm. He is the co-owner of Neuro-Luminance, a clinical service organization. He is the president of the International Society of Applied Neuroimaging. He is the CFO of the Neuro-Laser Foundation, a nonprofit foundation. Dr Paolo Cassano received funding from the Brain and Behavior Research Foundation; Photothera Inc and from the Dupont Warren Fellowship (Harvard Medical School) to conduct research on NIR light for the treatment of major depressive disorder. NR 162 TC 10 Z9 11 U1 2 U2 10 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-2021 J9 NEUROPSYCH DIS TREAT JI Neuropsychiatr. Dis. Treat. PY 2015 VL 11 BP 2159 EP 2175 DI 10.2147/NDT.S65809 PG 17 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CP7IM UT WOS:000360060500003 PM 26347062 ER PT J AU Rodriguez, KL Burkitt, KH Bayliss, NK Skoko, JE Switzer, GE Zickmund, SL Fine, MJ Macpherson, DS AF Rodriguez, Keri L. Burkitt, Kelly H. Bayliss, Nichole K. Skoko, Jennifer E. Switzer, Galen E. Zickmund, Susan L. Fine, Michael J. Macpherson, David S. TI Veteran, Primary Care Provider, and Specialist Satisfaction With Electronic Consultation SO JMIR MEDICAL INFORMATICS LA English DT Article DE access; rural health; referral and consultation; patient satisfaction; veterans ID RANDOMIZED CONTROLLED-TRIAL; PATIENT SATISFACTION; RURAL VETERANS; HEALTH-CARE; TELEMEDICINE AB Background: Access to specialty care is challenging for veterans in rural locations. To address this challenge, in December 2009, the Veterans Affairs (VA) Pittsburgh Healthcare System (VAPHS) implemented an electronic consultation (e-consult) program to provide primary care providers (PCPs) and patients with enhanced specialty care access. Objective: The aim of this quality improvement (QI) project evaluation was to: (1) assess satisfaction with the e-consult process, and (2) identify perceived facilitators and barriers to using the e-consult program. Methods: We conducted semistructured telephone interviews with veteran patients (N=15), Community Based Outpatient Clinic (CBOC) PCPs (N=15), and VA Pittsburgh specialty physicians (N=4) who used the e-consult program between December 2009 to August 2010. Participants answered questions regarding satisfaction in eight domains and identified factors contributing to their responses. Results: Most participants were white (patients=87%; PCPs=80%; specialists=75%) and male (patients=93%; PCPs=67%; specialists=75%). On average, patients had one e-consult (SD 0), PCPs initiated 6 e-consults (SD 6), and VAPHS specialists performed 17 e-consults (SD 11). Patients, PCPs, and specialty physicians were satisfied with e-consults median (range) of 5.0 (4-5) on 1-5 Likert-scale, 4.0 (3-5), and 3.5 (3-5) respectively. The most common reason why patients and specialists reported increased overall satisfaction with e-consults was improved communication, whereas improved timeliness of care was the most common reason for PCPs. Communication was the most reported perceived barrier and facilitator to e-consult use. Conclusions: Veterans and VA health care providers were satisfied with the e-consult process. Our findings suggest that while the reasons for satisfaction with e-consult differ somewhat for patients and physicians, e-consult may be a useful tool to improve VA health care system access for rural patients. C1 [Rodriguez, Keri L.; Burkitt, Kelly H.; Switzer, Galen E.; Zickmund, Susan L.; Fine, Michael J.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. [Rodriguez, Keri L.; Switzer, Galen E.; Zickmund, Susan L.; Fine, Michael J.; Macpherson, David S.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15213 USA. [Rodriguez, Keri L.] VA Pittsburgh Healthcare Syst, Vet Engn Resource Ctr, Pittsburgh, PA 15240 USA. [Bayliss, Nichole K.] Chatham Univ, Dept Psychol, Pittsburgh, PA USA. [Bayliss, Nichole K.] Chatham Univ, Dept Social Work Criminol, Pittsburgh, PA USA. [Skoko, Jennifer E.] VA Pittsburgh Healthcare Syst, Facil Management Serv, Pittsburgh, PA 15240 USA. [Switzer, Galen E.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Switzer, Galen E.] Univ Pittsburgh, Clin & Translat Sci Inst, Pittsburgh, PA USA. [Macpherson, David S.] Vet Integrated Serv Network 4 VISN 4 Healthcare N, Pittsburgh, PA USA. RP Rodriguez, KL (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Bldg 30,Univ Dr C 151C, Pittsburgh, PA 15240 USA. EM keri.rodriguez@va.gov NR 24 TC 5 Z9 5 U1 2 U2 3 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 2291-9694 J9 JMIR MED INF JI JMIR Med. Inf. PD JAN-MAR PY 2015 VL 3 IS 1 AR e5 DI 10.2196/medinform.3725 PG 14 WC Medical Informatics SC Medical Informatics GA CP3ON UT WOS:000359789800009 PM 25589233 ER PT J AU Landman, A Emani, S Carlile, N Rosenthal, DI Semakov, S Pallin, DJ Poon, EG AF Landman, Adam Emani, Srinivas Carlile, Narath Rosenthal, David I. Semakov, Simon Pallin, Daniel J. Poon, Eric G. TI A Mobile App for Securely Capturing and Transferring Clinical Images to the Electronic Health Record: Description and Preliminary Usability Study SO JMIR MHEALTH AND UHEALTH LA English DT Article DE mobile phone; photographs; electronic health records; telemedicine ID DIGITAL PHOTOGRAPHY; TELEDERMATOLOGY; FACILITATORS; DIAGNOSIS; BARRIERS; SYSTEMS AB Background: Photographs are important tools to record, track, and communicate clinical findings. Mobile devices with high-resolution cameras are now ubiquitous, giving clinicians the opportunity to capture and share images from the bedside. However, secure and efficient ways to manage and share digital images are lacking. Objective: The aim of this study is to describe the implementation of a secure application for capturing and storing clinical images in the electronic health record (EHR), and to describe initial user experiences. Methods: We developed CliniCam, a secure Apple iOS (iPhone, iPad) application that allows for user authentication, patient selection, image capture, image annotation, and storage of images as a Portable Document Format (PDF) file in the EHR. We leveraged our organization's enterprise service-oriented architecture to transmit the image file from CliniCam to our enterprise clinical data repository. There is no permanent storage of protected health information on the mobile device. CliniCam also required connection to our organization's secure WiFi network. Resident physicians from emergency medicine, internal medicine, and dermatology used CliniCam in clinical practice for one month. They were then asked to complete a survey on their experience. We analyzed the survey results using descriptive statistics. Results: Twenty-eight physicians participated and 19/28 (68%) completed the survey. Of the respondents who used CliniCam, 89% found it useful or very useful for clinical practice and easy to use, and wanted to continue using the app. Respondents provided constructive feedback on location of the photos in the EHR, preferring to have photos embedded in (or linked to) clinical notes instead of storing them as separate PDFs within the EHR. Some users experienced difficulty with WiFi connectivity which was addressed by enhancing CliniCam to check for connectivity on launch. Conclusions: CliniCam was implemented successfully and found to be easy to use and useful for clinical practice. CliniCam is now available to all clinical users in our hospital, providing a secure and efficient way to capture clinical images and to insert them into the EHR. Future clinical image apps should more closely link clinical images and clinical documentation and consider enabling secure transmission over public WiFi or cellular networks. C1 [Landman, Adam; Pallin, Daniel J.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Landman, Adam; Emani, Srinivas; Carlile, Narath; Pallin, Daniel J.] Harvard Univ, Sch Med, Boston, MA USA. [Emani, Srinivas; Carlile, Narath] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Rosenthal, David I.] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. [Rosenthal, David I.] US Dept Vet Affairs, West Haven, CT USA. [Semakov, Simon] Solaris Dev Inc, Newton, MA USA. [Poon, Eric G.] Boston Univ, Sch Med, Dept Med, Boston Med Ctr, Boston, MA 02118 USA. RP Landman, A (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. EM alandman@partners.org RI Pallin, Daniel/H-6382-2013 OI Pallin, Daniel/0000-0002-8517-9702 NR 21 TC 14 Z9 14 U1 3 U2 20 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 2291-5222 J9 JMIR MHEALTH UHEALTH JI JMIR mHealth uHealth PD JAN-MAR PY 2015 VL 3 IS 1 AR e1 DI 10.2196/mhealth.3481 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA CP3OX UT WOS:000359791000008 PM 25565678 ER PT S AU Gomez-Garcia, PA Arranz, A Fresno, M Desco, M Mahmood, U Vaquero, JJ Ripoll, J AF Aurelio Gomez-Garcia, Pablo Arranz, Alicia Fresno, Manuel Desco, Manuel Mahmood, Umar Jose Vaquero, Juan Ripoll, Jorge BE Kurachi, C Svanberg, K Tromberg, BJ Bagnato, VS TI Fluorescence multi-scale endoscopy and its applications in the study and diagnosis of gastro-intestinal diseases: set-up design and software implementation SO BIOPHOTONICS SOUTH AMERICA SE Proceedings of SPIE LA English DT Proceedings Paper CT Joint Meeting of the 1st SPIE Conference on Biophotonics South America (BSA) / 15th World Congress of the International-Photodynamic-Association (IPA) CY MAY 23-25, 2015 CL Rio de Janeiro, BRAZIL SP SPIE, Int Photodynam Assoc, FAPESP, Conselho Nacl Desenvolvimento Cientifico & Tecnologico DE Endoscopy; Endomicroscopy; Fiber bundle; Fluorescence; Scan; Software; Cell imaging ID IN-VIVO; CONFOCAL ENDOMICROSCOPY; ULCERATIVE-COLITIS; UPPER-GI; NEOPLASIA AB Endoscopy is frequently used in the diagnosis of several gastro-intestinal pathologies as Crohn disease, ulcerative colitis or colorectal cancer. It has great potential as a non-invasive screening technique capable of detecting suspicious alterations in the intestinal mucosa, such as inflammatory processes. However, these early lesions usually cannot be detected with conventional endoscopes, due to lack of cellular detail and the absence of specific markers. Due to this lack of specificity, the development of new endoscopy technologies, which are able to show microscopic changes in the mucosa structure, are necessary. We here present a confocal endomicroscope, which in combination with a wide field fluorescence endoscope offers fast and specific macroscopic information through the use of activatable probes and a detailed analysis at cellular level of the possible altered tissue areas. This multi-modal and multi-scale imaging module, compatible with commercial endoscopes, combines near-infrared fluorescence (NIRF) measurements (enabling specific imaging of markers of disease and prognosis) and confocal endomicroscopy making use of a fiber bundle, providing a cellular level resolution. The system will be used in animal models exhibiting gastro-intestinal diseases in order to analyze the use of potential diagnostic markers in colorectal cancer. In this work, we present in detail the set-up design and the software implementation in order to obtain simultaneous RGB/NIRF measurements and short confocal scanning times. C1 [Aurelio Gomez-Garcia, Pablo; Desco, Manuel; Jose Vaquero, Juan; Ripoll, Jorge] Univ Carlos III Madrid, Dept Bioengn & Aerosp Engn, Madrid 28911, Spain. [Aurelio Gomez-Garcia, Pablo; Desco, Manuel; Jose Vaquero, Juan; Ripoll, Jorge] Hosp Gregorio Maranon, Inst Invest Sanitaria, Expt Med & Surg Unit, Madrid 28007, Spain. [Arranz, Alicia; Fresno, Manuel] CSIC, Ctr Mol Biol Severo Ochoa CBMSO, Dept Cell Biol & Immunol, Madrid, Spain. [Mahmood, Umar] Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Charlestown, MA 02129 USA. RP Gomez-Garcia, PA (reprint author), Univ Carlos III Madrid, Dept Bioengn & Aerosp Engn, Madrid 28911, Spain. RI Arranz, Alicia/F-7477-2010; Desco, Manuel/D-2822-2009; Ripoll, Jorge/J-8134-2012; Vaquero, Juan Jose/D-3033-2009 OI Arranz, Alicia/0000-0002-5212-3024; Desco, Manuel/0000-0003-0989-3231; Ripoll, Jorge/0000-0001-8856-7738; Vaquero, Juan Jose/0000-0001-9200-361X NR 19 TC 0 Z9 0 U1 4 U2 7 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-62841-696-1 J9 PROC SPIE PY 2015 VL 9531 AR 953111 DI 10.1117/12.2189960 PG 10 WC Microscopy; Optics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Microscopy; Optics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA BD3CG UT WOS:000359467600013 ER PT J AU Chen, XZ Zhao, SF Song, Y Shi, YJ Leak, RK Cao, GD AF Chen, Xinzhi Zhao, Shangfeng Song, Yang Shi, Yejie Leak, Rehana K. Cao, Guodong TI The Role of Nicotinamide Phosphoribosyltransferase in Cerebral Ischemia SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review DE Adipokine; Brain ischemia; Intracerebroventricular; Mouse; Neuroprotection; Reperfusion injury; Stroke; Vascular biology ID COLONY-ENHANCING FACTOR; POTENT ANTITUMOR-ACTIVITY; TYPE-2 DIABETES-MELLITUS; REGULATES CELL-SURVIVAL; HUMAN FETAL MEMBRANES; VISFATIN GENE PBEF1; NAD BIOSYNTHESIS; WHITE-MATTER; MOUSE MODEL; NEUROPROTECTIVE EFFICACY AB As recombinant tissue plasminogen activator is the only drug approved for the clinical treatment of acute ischemic stroke, there is an urgent unmet need for novel stroke treatments. Endogenous defense mechanisms against stroke may hold the key to new therapies for stroke. A large number of studies suggest that nicotinamide phosphoribosyl-transferase (NAMPT) is an attractive candidate to improve post-stroke recovery. NAMPT is a multifunctional protein and plays important roles in immunity, metabolism, aging, inflammation, and stress responses. NAMPT exists in both the intracellular and extracellular space. As a rate-limiting enzyme, the intracellular form (iNAMPT) catalyzes the first step in the biosynthesis of nicotinamide adenine dinucleotide (NAD) from nicotinamide. iNAMPT closely regulates energy metabolism, enhancing the proliferation of endothelial cells, inhibiting apoptosis, regulating vascular tone, and stimulating autophagy in disease conditions such as stroke. Extracellular NAMPT (eNAMPT) is also known as visfatin (visceral fat-derived adipokine) and has pleotropic effects. It is widely believed that the diverse biological functions of eNAMPT are attributed to its NAMPT enzymatic activity. However, the effects of eNAMPT on ischemic injury are still controversial. Some authors have argued that eNAMPT exacerbates ischemic neuronal injury non-enzymatically by triggering the release of TNF-alpha from glial cells. In addition, NAMPT also participates in several pathophysiological processes such as hypertension, atherosclerosis, and ischemic heart disease. Thus, it remains unclear under what conditions NAMPT is beneficial or destructive. Recent work using in vitro and in vivo genetic/pharmacologic manipulations, including our own studies, has greatly improved our understanding of NAMPT. This review focuses on the multifaceted and complex roles of NAMPT under both normal and ischemic conditions. C1 [Chen, Xinzhi; Zhao, Shangfeng; Song, Yang; Shi, Yejie; Leak, Rehana K.; Cao, Guodong] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15260 USA. [Zhao, Shangfeng] Capital Med Univ, Beijing Tongren Hosp, Dept Neurosurg, Beijing 100053, Peoples R China. [Leak, Rehana K.] Duquesne Univ, Div Pharmaceut Sci, Pittsburgh, PA 15282 USA. [Cao, Guodong] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15240 USA. RP Chen, XZ (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15260 USA. EM chenx5@upmc.edu OI Leak, Rehana/0000-0003-2817-7417; Shi, Yejie/0000-0001-7502-9201 FU NIH [R01 NS079345]; VA Merit Review grants [RX000199 / BX002346] FX We thank all the authors who contributed to this field of work and apologize to those whose works are not directly cited in this review. This work was supported in part by NIH grants R01 NS079345 and VA Merit Review grants RX000199 / BX002346 (Dr. Cao). NR 101 TC 0 Z9 0 U1 3 U2 8 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 EI 1873-4294 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2015 VL 15 IS 21 BP 2211 EP 2221 DI 10.2174/1568026615666150610142234 PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA CO7ZS UT WOS:000359384100007 PM 26059356 ER PT J AU Yu, XC Zhu, B Lin, ZX Qiao, HF Kong, J Gao, XY AF Yu, Xiaochun Zhu, Bing Lin, Zhixiu Qiao, Haifa Kong, Jian Gao, Xinyan TI Acupoint Sensitization, Acupuncture Analgesia, Acupuncture on Visceral Functional Disorders, and Its Mechanism SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Editorial Material C1 [Yu, Xiaochun; Zhu, Bing; Gao, Xinyan] China Acad Chinese Med Sci, Inst Acupuncture, Beijing 100700, Peoples R China. [Lin, Zhixiu] Chinese Univ Hong Kong, Fac Med, Sch Chinese Med, Shatin, Hong Kong, Peoples R China. [Qiao, Haifa] Florida State Univ, Coll Med, Dept Biomed Sci, Tallahassee, FL 32306 USA. [Kong, Jian] Massachusetts Gen Hosp, Charlestown, MA USA. RP Yu, XC (reprint author), China Acad Chinese Med Sci, Inst Acupuncture, 16 Nanxiaojie, Beijing 100700, Peoples R China. EM yuxc@mail.cintcm.ac.cn RI Lin, Zhi-Xiu /H-2807-2016 NR 0 TC 1 Z9 1 U1 1 U2 7 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 2015 AR 171759 DI 10.1155/2015/171759 PG 1 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA CP0MN UT WOS:000359569500001 ER PT J AU Rinne, ST Liu, CF Feemster, LC Collins, BF Bryson, CL O'Riordan, TG Au, DH AF Rinne, Seppo T. Liu, Chuan-Fen Feemster, Laura C. Collins, Bridget F. Bryson, Christopher L. O'Riordan, Thomas G. Au, David H. TI Thiazolidinediones are associated with a reduced risk of COPD exacerbations SO INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE LA English DT Article DE peroxisome proliferator-activated receptors; glitazones; COPD exacerbation; inflammation; cohort study ID OBSTRUCTIVE PULMONARY-DISEASE; PROLIFERATOR-ACTIVATED RECEPTORS; SMOOTH-MUSCLE-CELLS; PPAR-GAMMA; HEART-FAILURE; ASTHMA; CORTICOSTEROIDS; ROSIGLITAZONE; INFLAMMATION; MANAGEMENT AB Background: Thiazolidinediones (TZDs) are oral antihyperglycemic medications that are selective agonists to peroxisome proliferator-activated receptor gamma and have been shown to have potent anti-inflammatory effects in the lung. Objective: The purpose of this study was to assess whether exposure to TZDs is associated with a decreased risk of chronic obstructive pulmonary disease (COPD) exacerbation. Methods: A cohort study was performed by collecting data on all US veterans with diabetes and COPD who were prescribed oral antihyperglycemic medications during from period of October 1, 2005 to September 30, 2007. Patients who had two or more prescriptions for TZDs were compared with patients who had two or more prescriptions for an alternative oral anti-hyperglycemic medication. Multivariable negative binomial regression was performed with adjustment for potential confounding factors. The primary outcome was COPD exacerbations, including both inpatient and outpatient exacerbations. Results: We identified 7,887 veterans who were exposed to TZD and 42,347 veterans who were exposed to non-TZD oral diabetes medications. COPD exacerbations occurred in 1,258 (16%) of the TZD group and 7,789 (18%) of the non-TZD group. In multivariable negative binomial regression, there was a significant reduction in the expected number of COPD exacerbations among patients who were exposed to TZDs with an incidence rate ratio of 0.86 (95% CI 0.81-0.92). Conclusion: Exposure to TZDs was associated with a small but significant reduction in risk for COPD exacerbation among diabetic patients with COPD. C1 [Rinne, Seppo T.] VA Connecticut Healthcare Syst, Dept Vet Affairs, West Haven, CT 06516 USA. [Rinne, Seppo T.] Yale Univ, Div Pulm & Crit Care, New Haven, CT USA. [Liu, Chuan-Fen; Feemster, Laura C.; Collins, Bridget F.; Bryson, Christopher L.; Au, David H.] VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Seattle, WA USA. [Liu, Chuan-Fen; Au, David H.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Feemster, Laura C.; Collins, Bridget F.] Univ Washington, Div Pulm & Crit Care, Seattle, WA 98195 USA. [Bryson, Christopher L.] Univ Washington, Div Gen Internal Med, Seattle, WA 98195 USA. [O'Riordan, Thomas G.] Gilead Sci Inc, Seattle, WA USA. RP Rinne, ST (reprint author), VA Connecticut Healthcare Syst, Dept Vet Affairs, 950 Campbell Ave,Bldg 35a,Room 2-234, West Haven, CT 06516 USA. EM seppo.rinne@va.gov FU VA HSRD grant [IIR 07-068-2]; Gilead Sciences Inc.; NIH NHLBI [K23 HL111116] FX Research funding for this project was from a VA HSR&D grant (IIR 07-068-2) along with funding from Gilead Sciences Inc. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States Government. Dr Feemster is supported by the NIH NHLBI (K23 HL111116). NR 37 TC 0 Z9 0 U1 1 U2 2 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-2005 J9 INT J CHRONIC OBSTR JI Int. J. Chronic Obstr. Pulm. Dis. PY 2015 VL 10 BP 1591 EP 1597 DI 10.2147/COPD.S82643 PG 7 WC Respiratory System SC Respiratory System GA CO6ZI UT WOS:000359306500001 PM 26300638 ER PT J AU Kim, JY Ryu, JH Schellingerhout, D Sun, IC Lee, SK Jeon, S Kim, J Kwon, IC Nahrendorf, M Ahn, CH Kim, K Kim, DE AF Kim, Jeong-Yeon Ryu, Ju Hee Schellingerhout, Dawid Sun, In-Cheol Lee, Su-Kyoung Jeon, Sangmin Kim, Jiwon Kwon, Ick Chan Nahrendorf, Matthias Ahn, Cheol-Hee Kim, Kwangmeyung Kim, Dong-Eog TI Direct Imaging of Cerebral Thromboemboli Using Computed Tomography and Fibrin-targeted Gold Nanoparticles SO THERANOSTICS LA English DT Article DE direct thrombus imaging; gold nanoparticles; computed tomography; cerebral infarction; molecular imaging ID MYOCARDIAL-INFARCTION; THROMBUS FORMATION; ISCHEMIC-STROKE; CONTRAST AGENT; IN-VIVO; THERAPY; RESISTANCE; MODELS AB Computed tomography (CT) is the current standard for time-critical decision-making in stroke patients, informing decisions on thrombolytic therapy with tissue plasminogen activator (tPA), which has a narrow therapeutic index. We aimed to develop a CT-based method to directly visualize cerebrovascular thrombi and guide thrombolytic therapy. Glycol-chitosan-coated gold nanoparticles (GC-AuNPs) were synthesized and conjugated to fibrin-targeting peptides, forming fib-GC-AuNP. This targeted imaging agent and non-targeted control agent were characterized in vitro and in vivo in C57BI/6 mice (n = 107) with FeCl3-induced carotid thrombosis and/or embolic ischemic stroke. Fibrin-binding capacity was superior with fib-GC-AuNPs compared to GC-AuNPs, with thrombi visualized as high density on microCT (mCT). mCT imaging using fib-GC-AuNP allowed the prompt detection and quantification of cerebral thrombi, and monitoring of tPA-mediated thrombolytic effect, which reflected histological stroke outcome. Furthermore, recurrent thrombosis could be diagnosed by mCT without further nanoparticle administration for up to 3 weeks. fib-GC-AuNP-based direct cerebral thrombus imaging greatly enhance the value and information obtainable by regular CT, has multiple uses in basic/translational vascular research, and will likely allow personalized thrombolytic therapy in clinic by a) optimizing tPA-dosing to match thrombus burden, b) enabling the rational triage of patients to more radical therapies such as endovascular clot-retrieval, and c) potentially serving as a theranostic platform for targeted delivery of concurrent thrombolysis. C1 [Kim, Jeong-Yeon; Lee, Su-Kyoung; Kim, Jiwon; Kim, Dong-Eog] Dongguk Univ, Coll Med, Mol Imaging & Neurovasc Res Lab, Goyang, South Korea. [Ryu, Ju Hee; Sun, In-Cheol; Jeon, Sangmin; Kwon, Ick Chan; Kim, Kwangmeyung] Korea Inst Sci & Technol, Biomed Res Inst, Seoul, South Korea. [Schellingerhout, Dawid] Univ Texas MD Anderson Canc Ctr, Dept Radiol, Houston, TX 77030 USA. [Schellingerhout, Dawid] Univ Texas MD Anderson Canc Ctr, Dept Expt Diagnost Imaging, Houston, TX 77030 USA. [Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Nahrendorf, Matthias] Harvard Univ, Sch Med, Boston, MA USA. [Ahn, Cheol-Hee] Seoul Natl Univ, Dept Mat Sci & Engn, Res Inst Adv Mat, Seoul, South Korea. RP Kim, DE (reprint author), Dongguk Univ, Ilsan Hosp, Mol Imaging & Neurovasc Res Lab, 814 Siksa Dong, Goyang, South Korea. EM kim@kist.re.kr; kdongeog@duih.org FU Bio & Medical Technology Development Program of the National Research Foundation [2010-0019862]; Korea Healthcare Technology R&D Project, Ministry of Health and Welfare - Korean government [A120099, A121996] FX The authors thank Jin-Yong Park and Dr. Wi-Sun Ryu for their valuable comments on this study. This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (2010-0019862) and the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare (A120099, A121996), funded by the Korean government. NR 29 TC 10 Z9 10 U1 4 U2 10 PU IVYSPRING INT PUBL PI LAKE HAVEN PA PO BOX 4546, LAKE HAVEN, NSW 2263, AUSTRALIA SN 1838-7640 J9 THERANOSTICS JI Theranostics PY 2015 VL 5 IS 10 BP 1098 EP 1114 DI 10.7150/thno.11679 PG 17 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA CO9DK UT WOS:000359472700005 PM 26199648 ER PT J AU Landman, A Emani, S Carlile, N Rosenthal, DI Semakov, S Pallin, DJ Poon, EG AF Landman, Adam Emani, Srinivas Carlile, Narath Rosenthal, David I. Semakov, Simon Pallin, Daniel J. Poon, Eric G. TI A Mobile App for Securely Capturing and Transferring Clinical Images to the Electronic Health Record: Description and Preliminary Usability Study SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE mobile phone; photographs; electronic health records; telemedicine ID DIGITAL PHOTOGRAPHY; CARE; TELEDERMATOLOGY; FACILITATORS; TECHNOLOGY; DIAGNOSIS; BARRIERS; SYSTEMS AB Background: Photographs are important tools to record, track, and communicate clinical findings. Mobile devices with high-resolution cameras are now ubiquitous, giving clinicians the opportunity to capture and share images from the bedside. However, secure and efficient ways to manage and share digital images are lacking. Objective: The aim of this study is to describe the implementation of a secure application for capturing and storing clinical images in the electronic health record (EHR), and to describe initial user experiences. Methods: We developed CliniCam, a secure Apple iOS (iPhone, iPad) application that allows for user authentication, patient selection, image capture, image annotation, and storage of images as a Portable Document Format (PDF) file in the EHR. We leveraged our organization's enterprise service-oriented architecture to transmit the image file from CliniCam to our enterprise clinical data repository. There is no permanent storage of protected health information on the mobile device. CliniCam also required connection to our organization's secure WiFi network. Resident physicians from emergency medicine, internal medicine, and dermatology used CliniCam in clinical practice for one month. They were then asked to complete a survey on their experience. We analyzed the survey results using descriptive statistics. Results: Twenty-eight physicians participated and 19/28 (68%) completed the survey. Of the respondents who used CliniCam, 89% found it useful or very useful for clinical practice and easy to use, and wanted to continue using the app. Respondents provided constructive feedback on location of the photos in the EHR, preferring to have photos embedded in (or linked to) clinical notes instead of storing them as separate PDFs within the EHR. Some users experienced difficulty with WiFi connectivity which was addressed by enhancing CliniCam to check for connectivity on launch. Conclusions: CliniCam was implemented successfully and found to be easy to use and useful for clinical practice. CliniCam is now available to all clinical users in our hospital, providing a secure and efficient way to capture clinical images and to insert them into the EHR. Future clinical image apps should more closely link clinical images and clinical documentation and consider enabling secure transmission over public WiFi or cellular networks. C1 [Landman, Adam; Pallin, Daniel J.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Landman, Adam; Emani, Srinivas; Carlile, Narath; Pallin, Daniel J.] Harvard Univ, Sch Med, Boston, MA USA. [Emani, Srinivas; Carlile, Narath] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Rosenthal, David I.] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. [Rosenthal, David I.] US Dept Vet Affairs, West Haven, CT USA. [Semakov, Simon] Solaris Dev Inc, Newton, MA USA. [Poon, Eric G.] Boston Univ, Sch Med, Dept Med, Boston Med Ctr, Boston, MA 02118 USA. RP Landman, A (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. EM alandman@partners.org FU Brigham and Women's Hospital Health Information Technology Innovation Program FX We thank Nina Plaks, Chioma Agbo, MD, Kara Backman, Stephen Clay, Janice Grillo, Janice Cutone, Kevin Littlefield, Jacqueline Raymond, Scott Guelich, MD, and multiple Partners Healthcare information services teams for their assistance with design and development of the application. We also appreciate assistance with the survey from Vladmir Suric (Partners Healthcare, Wellesley, MA). Generous funding for this project was provided by a grant from the Brigham and Women's Hospital Health Information Technology Innovation Program. The sponsor had no role in the design and conduct of the study; and collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. NR 22 TC 0 Z9 0 U1 4 U2 12 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PD JAN PY 2015 VL 17 IS 1 DI 10.2196/mhealth.3481 PG 8 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA AY0YH UT WOS:000347320100004 ER PT J AU Toda, K Zeredo, JL Uchida, S Napadow, V AF Toda, Kazuo Zeredo, Jorge L. Uchida, Sae Napadow, Vitaly TI Traditional Chinese Medicine and Autonomic Disorders SO EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE LA English DT Editorial Material C1 [Toda, Kazuo] Nagasaki Univ, Grad Sch Biomed Sci, Integrat Sensory Physiol, Nagasaki 8528588, Japan. [Zeredo, Jorge L.] Univ Brasilia, Grad Program Hlth Sci, BR-70910900 Brasilia, DF, Brazil. [Uchida, Sae] Tokyo Metropolitan Inst Gerontol, Dept Auton Nervous Syst, Tokyo, Tokyo 1730015, Japan. [Napadow, Vitaly] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Toda, K (reprint author), Nagasaki Univ, Grad Sch Biomed Sci, Integrat Sensory Physiol, Nagasaki 8528588, Japan. EM k-toda@nagasaki-u.ac.jp NR 0 TC 0 Z9 0 U1 0 U2 0 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 2015 AR 429181 DI 10.1155/2015/429181 PG 2 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA CO5NS UT WOS:000359206400001 ER PT J AU Lee, YJ Choi, HS Seo, MJ Jeon, HJ Kim, KJ Lee, BY AF Lee, Yeon-Joo Choi, Hyeon-Son Seo, Min-Jung Jeon, Hui-Jeon Kim, Kui-Jin Lee, Boo-Yong TI Kaempferol suppresses lipid accumulation by inhibiting early adipogenesis in 3T3-L1 cells and zebrafish SO FOOD & FUNCTION LA English DT Article ID CANCER CHEMOPREVENTION; TRANSCRIPTION FACTORS; EXPRESSION; EXTRACT; OBESITY; DIFFERENTIATION; HOMEOSTASIS; ADIPOCYTES; METABOLISM; REGULATORS AB Kaempferol is a flavonoid present in Kaempferia galanga and Opuntia ficus indica var. saboten. Recent studies have suggested that it has anti-oxidant, anti-inflammatory, anti-cancer, and anti-obesity effects. In this study, we focused on the anti-adipogenic effects of kaempferol during adipocyte differentiation. The results showed that kaempferol inhibits lipid accumulation in adipocytes and zebrafish. Oil Red O and Nile Red staining showed that the number of intracellular lipid droplets decreased in adipocytes and zebrafish treated with kaempferol. LPAAT. (lysophosphatidic acid acyltransferase), lipin1, and DGAT1 (triglyceride synthetic enzymes) and FASN and SREBP-1C (fatty acid synthetic proteins) showed decreased expression levels in the presence of kaempferol. In addition, treatment of kaempferol showed an inhibitory activity on cell cycle progression. Kaempferol delayed cell cycle progression from the S to G2/M phase through the regulation of cyclins in a dose-dependent manner. Kaempferol blocked the phosphorylation of AKT (protein kinase B) and mammalian target of rapamycin (mTOR) signaling pathway during the early stages of adipogenesis. In addition, kaempferol down-regulated pro-early adipogenic factors such as CCAAT-enhancer binding proteins beta (C/EBP beta), and Kruppel-like factors (KLFs) 4 and 5, while anti-early adipogenic factors, such as KLF2 and pref-1(preadipocyte factor-1), were upregulated. These kaempferolmediated regulations of early adipogenic factors resulted in the attenuation of late adipogenic factors such as C/EBP alpha and peroxisome proliferator-activated receptor gamma (PPAR gamma). These results were supported in zebrafish based on the decrease in lipid accumulation and expression of adipogenic factors. Our results indicated that kaempferol might have an anti-obesity effect by regulating lipid metabolism. C1 [Lee, Yeon-Joo; Seo, Min-Jung; Jeon, Hui-Jeon; Lee, Boo-Yong] CHA Univ, Dept Food Sci & Biotechnol, Songnam 463400, Kyonggi, South Korea. [Choi, Hyeon-Son] Seoul Womens Univ, Dept Food Sci & Technol, Seoul 139774, South Korea. [Kim, Kui-Jin] Harvard Univ, Dept Med, Lab Lipid Med & Technol, Med Sch,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Lee, YJ (reprint author), CHA Univ, Dept Food Sci & Biotechnol, Songnam 463400, Kyonggi, South Korea. EM bylee@cha.ac.kr FU National Research Foundation of Korea (NRF) - Ministry of Education [2013R1A1A2064024] FX This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2013R1A1A2064024). NR 45 TC 8 Z9 8 U1 2 U2 11 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2042-6496 EI 2042-650X J9 FOOD FUNCT JI Food Funct. PY 2015 VL 6 IS 8 BP 2824 EP 2833 DI 10.1039/c5fo00481k PG 10 WC Biochemistry & Molecular Biology; Food Science & Technology SC Biochemistry & Molecular Biology; Food Science & Technology GA CO4KD UT WOS:000359128700042 PM 26174858 ER PT J AU Santos-Martinez, MJ Tomaszewski, KA Medina, C Bazou, D Gilmer, JF Radomski, MW AF Santos-Martinez, Maria J. Tomaszewski, Krzysztof A. Medina, Carlos Bazou, Despina Gilmer, John F. Radomski, Marek W. TI Pharmacological characterization of nanoparticle-induced platelet microaggregation using quartz crystal microbalance with dissipation: comparison with light aggregometry SO INTERNATIONAL JOURNAL OF NANOMEDICINE LA English DT Article DE platelet microaggregation; quartz crystal microbalance with dissipation; pharmacology; nanoparticles ID CORONARY-ARTERY-DISEASE; NITRIC-OXIDE; DRUG-DELIVERY; VASCULAR ENDOTHELIUM; SILICA NANOPARTICLES; INHALED PARTICLES; AGGREGATION; ASPIRIN; PROSTACYCLIN; ACTIVATION AB Background: Engineered nanoparticles (NPs) can induce platelet activation and aggregation, but the mechanisms underlying these interactions are not well understood. This could be due in part to use of devices that study platelet function under quasi-static conditions with low sensitivity to measure platelet microaggregation. Therefore, in this study we investigated the pharmacological pathways and regulators of NP-induced platelet microaggregation under flow conditions at nanoscale using quartz crystal microbalance with dissipation (QCM-D) and compared the data thus obtained with those generated by light aggregometry. Methods: Blood was collected from healthy volunteers, and platelet-rich plasma was obtained. Thrombin receptor-activating peptide, a potent stimulator of platelet function, and pharmacological inhibitors were used to modulate platelet microaggregation in the presence/absence of silica (10 nm and 50 nm) and polystyrene (23 nm) NPs. Light aggregometry was used to study platelet aggregation in macroscale. Optical, immunofluorescence, and scanning electron microscopy were also used to visualize platelet aggregates. Results: Platelet microaggregation was enhanced by thrombin receptor-activating peptide, whereas prostacyclin, nitric oxide donors, acetylsalicylic acid, and phenanthroline, but not adenosine diphosphate (ADP) blockers, were able to inhibit platelet microaggregation. NPs caused platelet microaggregation, an effect not detectable by light aggregometry. NP-induced microaggregation was attenuated by platelet inhibitors. Conclusion: NP-induced platelet microaggregation appears to involve classical proaggregatory pathways (thromboxane A(2)-mediated and matrix metalloproteinase-2-mediated) and can be regulated by endogenous (prostacyclin) and pharmacological (acetylsalicylic acid, phenanthroline, and nitric oxide donors) inhibitors of platelet function. Quartz crystal microbalance with dissipation, but not light aggregometry, is an appropriate method for studying NP-induced microaggregation. C1 [Santos-Martinez, Maria J.; Tomaszewski, Krzysztof A.; Medina, Carlos; Gilmer, John F.; Radomski, Marek W.] Univ Dublin, Sch Pharm & Pharmaceut Sci, Univ Dublin Trinity Coll, Dublin, Ireland. [Santos-Martinez, Maria J.; Tomaszewski, Krzysztof A.; Medina, Carlos; Gilmer, John F.; Radomski, Marek W.] Univ Dublin, Trinity Biomed Sci Inst, Univ Dublin Trinity Coll, Dublin, Ireland. [Santos-Martinez, Maria J.] Univ Dublin, Sch Med, Univ Dublin Trinity Coll, Dublin, Ireland. [Tomaszewski, Krzysztof A.] Jagiellonian Univ, Dept Anat, Coll Med, Krakow, Poland. [Bazou, Despina] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. [Bazou, Despina] Harvard Univ, Sch Med, Boston, MA USA. [Radomski, Marek W.] Kardiomed Silesia, Zabrze, Poland. [Radomski, Marek W.] Med Univ Silesia, Katowice, Poland. RP Medina, C (reprint author), Univ Dublin Trinity Coll, Sch Pharm & Pharmaceut Sci, Panoz Inst, Dublin 2, Ireland. EM carlos.medina@tcd.ie FU Science Foundation Ireland (SFI) [S.F.I.O5/FE1/B862]; SFI-RFP grant [RFP/BMT2781]; Jagiellonian University Medical College statutory funds for young scientists FX The work was supported by a Science Foundation Ireland (SFI) principal investigator grant to MWR (S.F.I.O5/FE1/B862) and SFI-RFP grant (RFP/BMT2781) to CM. CM is an SFI Stokes lecturer. MJSM is an Ussher lecturer in Nanopharmaceutical Drug Discovery at Trinity College Dublin. KAT received funding from the Jagiellonian University Medical College statutory funds for young scientists. The authors would like to acknowledge Heath Bagshaw and Neal Leddy (Centre for Microscopy and Analysis) for their assistance with the scanning electron microscopy and Esther Rufino for technical assistance. NR 45 TC 2 Z9 2 U1 2 U2 9 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-2013 J9 INT J NANOMED JI Int. J. Nanomed. PY 2015 VL 10 BP 5107 EP 5119 DI 10.2147/IJN.S84305 PG 13 WC Nanoscience & Nanotechnology; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA CO8UH UT WOS:000359447100001 PM 26316743 ER PT J AU Guercio, BJ Donovan, NJ Munro, CE Aghjayan, SL Wigman, SE Locascio, JJ Amariglio, RE Rentz, DM Johnson, KA Sperling, RA Marshall, GA AF Guercio, Brendan J. Donovan, Nancy J. Munro, Catherine E. Aghjayan, Sarah L. Wigman, Sarah E. Locascio, Joseph J. Amariglio, Rebecca E. Rentz, Dorene M. Johnson, Keith A. Sperling, Reisa A. Marshall, Gad A. TI The Apathy Evaluation Scale: A Comparison of Subject, Informant, and Clinician Report in Cognitively Normal Elderly and Mild Cognitive Impairment SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Aged; Alzheimer's disease; apathy; mild cognitive impairment; symptom assessment ID ALZHEIMER-DISEASE CONSORTIUM; NEUROPSYCHIATRIC SYMPTOMS; OLDER-ADULTS; EXECUTIVE DYSFUNCTION; FUNCTIONAL IMPAIRMENT; AMYLOID BURDEN; CACHE COUNTY; DEMENTIA; INDIVIDUALS; INVENTORY AB Background: Apathy is a common neuropsychiatric symptom in Alzheimer's disease (AD) dementia and mild cognitive impairment (MCI). Detecting apathy accurately may facilitate earlier diagnosis of AD. The Apathy Evaluation Scale (AES) is a promising tool for measurement of apathy in prodromal and possibly preclinical AD. Objective: To compare the threeAESsub-scales-subject-reported (AES-S), informant-reported (AES-I), and clinician-reported (AES-C)-over time in individuals at risk for AD due to MCI and advanced age (cognitively normal [CN] elderly). Methods: Mixed effects longitudinal models were used to assess predictors of score for each AES sub-scale. Cox proportional hazards models were used to assess which AES sub-scales predict progression from MCI to AD dementia. Results: Fifty-seven MCI and 18 CN subjects (ages 53-86) were followed for 1.4 +/- 1.2 years and 0.7 +/- 0.7 years, respectively. Across the three mixed effects longitudinal models, the common findings were associations between greater apathy and greater years in study, a baseline diagnosis of MCI (compared to CN), and male gender. CN elderly self-reported greater apathy compared to that reported by informants and clinicians, while individuals with MCI under-reported their apathy compared to informants and clinicians. Of the three sub-scales, the AES-C best predicted transition from MCI to AD dementia. Conclusion: In a sample of CN elderly and elderly with MCI, apathy increased over time, particularly in men and those with MCI. AES-S scores may be more sensitive than AES-I and AES-C scores in CN elderly, but less reliable if subjects have MCI. Moreover, the AES-C sub-scale predicted progression from MCI to AD dementia. C1 [Guercio, Brendan J.; Donovan, Nancy J.; Amariglio, Rebecca E.; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.; Marshall, Gad A.] Harvard Univ, Sch Med, Boston, MA USA. [Guercio, Brendan J.; Donovan, Nancy J.; Aghjayan, Sarah L.; Amariglio, Rebecca E.; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.; Marshall, Gad A.] Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. [Donovan, Nancy J.; Aghjayan, Sarah L.; Wigman, Sarah E.; Amariglio, Rebecca E.; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.; Marshall, Gad A.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Donovan, Nancy J.; Amariglio, Rebecca E.; Rentz, Dorene M.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Munro, Catherine E.; Aghjayan, Sarah L.; Wigman, Sarah E.; Locascio, Joseph J.; Amariglio, Rebecca E.; Rentz, Dorene M.; Sperling, Reisa A.; Marshall, Gad A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Johnson, Keith A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Marshall, GA (reprint author), Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, 221 Longwood Ave,BL-104H, Boston, MA 02115 USA. EM gamarshall@partners.org FU Rosalinde and Arthur Gilbert Foundation/AFAR New Investigator Awards in Alzheimer's Disease; Massachusetts Alzheimer's Disease Research Center [P50 AG005134]; Harvard Aging Brain Study [P01 AGO36694, R01 AG037497]; Harvard Medical School Scholars in Medicine Office; Janssen Alzheimer Immunotherapy; Wyeth/Pfizer Pharmaceuticals; Eisai Inc.; Eli Lilly and Company; Avid Radiopharmaceuticals; Bristol-Myers-Squibb; [R01 AG027435]; [K23 AG033634]; [K24 AG035007] FX This research was supported by R01 AG027435, K23 AG033634, K24 AG035007, the Rosalinde and Arthur Gilbert Foundation/AFAR New Investigator Awards in Alzheimer's Disease, the Massachusetts Alzheimer's Disease Research Center (P50 AG005134), and the Harvard Aging Brain Study (P01 AGO36694, R01 AG037497). Authors have also received research salary support from the Harvard Medical School Scholars in Medicine Office.; The authors have received research salary support from Janssen Alzheimer Immunotherapy (GAM, REA), Wyeth/Pfizer Pharmaceuticals (GAM, REA), Eisai Inc. (GAM), Eli Lilly and Company (GAM), Avid Radiopharmaceuticals (KAJ), and Bristol-Myers-Squibb (GAM, RAS). NR 71 TC 3 Z9 3 U1 2 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2015 VL 47 IS 2 BP 421 EP 432 DI 10.3233/JAD-150146 PG 12 WC Neurosciences SC Neurosciences & Neurology GA CO5IC UT WOS:000359191800013 PM 26401564 ER PT J AU Korbelik, M Hamblin, MR AF Korbelik, Mladen Hamblin, Michael R. TI The impact of macrophage-cancer cell interaction on the efficacy of photodynamic therapy SO PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES LA English DT Review ID TUMOR-ASSOCIATED MACROPHAGES; SCAVENGER-RECEPTOR; SULFONATED PHTHALOCYANINE; MURINE MACROPHAGES; APOPTOTIC CELLS; UP-REGULATION; SOLID TUMORS; COMPLEMENT; ACTIVATION; PHOTOFRIN AB Macrophages are one of the principal host cell populations in solid tumors. They are capable, due to their plasticity, of acquiring phenotypes that either combat (M1 type) or promote (M2 type) neoplastic growth. These cells, known as tumor-associated macrophages (TAMs), play complex but pivotal roles in the outcome of photodynamic therapy (PDT) of malignant lesions. Among the various parenchymal and stromal cell populations found in tumors, TAMs have been shown to have the greatest capacity for the uptake of systemically administered photosensitizers. Both the tumor-localizing property of photosensitizers and their tumor-localized fluorescence could be partly attributed to the activity of TAMs. Since resident TAMs with accumulated high photosensitizer content will sustain high degrees of PDT damage, this population (predominantly M2 in most tumors) is selectively destroyed, and during the ensuing inflammatory reaction is replaced with newly invading macrophages of M1 phenotype. These macrophages are sentinels responding to DAMP signals from PDT-treated tumor cells and in turn are mobilized to generate a variety of inflammatory/immune mediators and opsonins. They have a critical role in contributing to the therapeutic effect of PDT by mediating disposal of killed cancer cells and by processing/presenting tumor antigens to T lymphocytes. However, TAMs accumulating in the later post-PDT phase can acquire the M2 (healing) phenotype, and could have a role in tumor recurrence by releasing factors that promote angiogenesis and the survival/proliferation of remaining cancer cells. Various therapeutic strategies modulating TAM activity in the PDT response have potential for clinical use for improving PDT-mediated tumor control. C1 [Korbelik, Mladen] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [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 USA. RP Korbelik, M (reprint author), British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. EM mkorbelik@bccrc.ca; hamblin@helix.mghb.harcardcedu FU Canadian Cancer Society [70113]; US NIH [R01-CA77475, R01-CA/AI838801, R01-AI050875] FX Research funding for Mladen Korbelik was provided by Canadian Cancer Society (grant # 701132) and US NIH grant R01-CA77475. Michael R Hamblin was supported by US NIH grants R01-CA/AI838801 and R01-AI050875. NR 67 TC 6 Z9 6 U1 0 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1474-905X EI 1474-9092 J9 PHOTOCH PHOTOBIO SCI JI Photochem. Photobiol. Sci. PY 2015 VL 14 IS 8 BP 1403 EP 1409 DI 10.1039/c4pp00451e PG 7 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA CN8YM UT WOS:000358732000005 PM 25620672 ER PT J AU Spring, BQ Rizvi, I Xu, N Hasan, T AF Spring, Bryan Q. Rizvi, Imran Xu, Nan Hasan, Tayyaba TI The role of photodynamic therapy in overcoming cancer drug resistance SO PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES LA English DT Review ID EPITHELIAL-MESENCHYMAL TRANSITION; ENDOTHELIAL GROWTH-FACTOR; SQUAMOUS-CELL CARCINOMA; PHASE-II TRIAL; OVARIAN-CANCER; PANCREATIC-CANCER; IN-VIVO; C-MET; PHOTOCHEMICAL INTERNALIZATION; PHTHALOCYANINE TETRASULFONATE AB Many modalities of cancer therapy induce mechanisms of treatment resistance and escape pathways during chronic treatments, including photodynamic therapy (PDT). It is conceivable that resistance induced by one treatment might be overcome by another treatment. Emerging evidence suggests that the unique mechanisms of tumor cell and microenvironment damage produced by PDT could be utilized to overcome cancer drug resistance, to mitigate the compensatory induction of survival pathways and even to re-sensitize resistant cells to standard therapies. Approaches that capture the unique features of PDT, therefore, offer promising factors for increasing the efficacy of a broad range of therapeutic modalities. Here, we highlight key preclinical findings utilizing PDT to overcome classical drug resistance or escape pathways and thus enhance the efficacy of many pharmaceuticals, possibly explaining the clinical observations of the PDT response to otherwise treatment-resistant diseases. With the development of nanotechnology, it is possible that light activation may be used not only to damage and sensitize tumors but also to enable controlled drug release to inhibit escape pathways that may lead to resistance or cell proliferation. C1 [Spring, Bryan Q.; Rizvi, Imran; Xu, Nan; Hasan, Tayyaba] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Spring, Bryan Q.; Rizvi, Imran; Xu, Nan; Hasan, Tayyaba] Harvard Univ, Sch Med, Boston, MA USA. [Rizvi, Imran] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Xu, Nan] Shanghai East Hosp, Dept Dermatol, Shanghai, Peoples R China. [Xu, Nan] Tongji Univ, Shanghai 200092, Peoples R China. [Hasan, Tayyaba] Harvard Univ, Div Hlth Sci & Technol, Cambridge, MA 02138 USA. [Hasan, Tayyaba] MIT, Cambridge, MA 02139 USA. RP Hasan, T (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM thasan@mgh.harvard.edu FU National Institutes of Health [R01-CA156177, R01-CA158415, R01-CA160998, P01-CA084203, K99-CA175292] FX This work was supported by National Institutes of Health Grants R01-CA156177, R01-CA158415, R01-CA160998 and P01-CA084203 (to T.H.); and, K99-CA175292 (to I.R.). NR 125 TC 23 Z9 23 U1 8 U2 32 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1474-905X EI 1474-9092 J9 PHOTOCH PHOTOBIO SCI JI Photochem. Photobiol. Sci. PY 2015 VL 14 IS 8 BP 1476 EP 1491 DI 10.1039/c4pp00495g PG 16 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA CN8YM UT WOS:000358732000011 PM 25856800 ER PT J AU Anzengruber, F Avci, P de Freitasa, LF Hamblin, MR AF Anzengruber, Florian Avci, Pinar de Freitasa, Lucas Freitas Hamblin, Michael R. TI T-cell mediated anti-tumor immunity after photodynamic therapy: why does it not always work and how can we improve it? SO PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES LA English DT Article ID NF-KAPPA-B; ENDOTHELIAL GROWTH-FACTOR; TUMOR-INFILTRATING LYMPHOCYTES; NATURAL-KILLER-CELLS; DENDRITIC CELLS; IN-VIVO; COMPLEMENT ACTIVATION; REGULATORY CELLS; CANCER-CELLS; SOLID TUMORS AB Photodynamic therapy (PDT) uses the combination of non-toxic photosensitizers and harmless light to generate reactive oxygen species that destroy tumors by a combination of direct tumor cell killing, vascular shutdown, and activation of the immune system. It has been shown in some animal models that mice that have been cured of cancer by PDT, may exhibit resistance to rechallenge. The cured mice can also possess tumor specific T-cells that recognize defined tumor antigens, destroy tumor cells in vitro, and can be adoptively transferred to protect naive mice from cancer. However, these beneficial outcomes are the exception rather than the rule. The reasons for this lack of consistency lie in the ability of many tumors to suppress the host immune system and to actively evade immune attack. The presence of an appropriate tumor rejection antigen in the particular tumor cell line is a requisite for T-cell mediated immunity. Regulatory T-cells (CD25+, Foxp3+) are potent inhibitors of anti-tumor immunity, and their removal by low dose cyclophosphamide can potentiate the PDT-induced immune response. Treatments that stimulate dendritic cells (DC) such as CpG oligonucleotide can overcome tumor-induced DC dysfunction and improve PDT outcome. Epigenetic reversal agents can increase tumor expression of MHC class I and also simultaneously increase expression of tumor antigens. A few clinical reports have shown that anti-tumor immunity can be generated by PDT in patients, and it is hoped that these combination approaches may increase tumor cures in patients. C1 [Anzengruber, Florian; Avci, Pinar; de Freitasa, Lucas Freitas; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Anzengruber, Florian; Avci, Pinar; de Freitasa, Lucas Freitas; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Avci, Pinar] Semmelweis Univ, Sch Med, Dept Dermatol Dermatooncol & Venerol, H-1085 Budapest, Hungary. [de Freitasa, Lucas Freitas] Univ Sao Paulo, Programa Pos Grad Interunidades Bioengn, Sao Carlos, Brazil. [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 FU FAPESP [2013/20599-4]; US NIH [R01AI050875] FX Lucas Freitas de Freitas was supported by FAPESP grant 2013/20599-4.; Michael R Hamblin was supported by US NIH grant R01AI050875. NR 209 TC 8 Z9 8 U1 5 U2 19 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1474-905X EI 1474-9092 J9 PHOTOCH PHOTOBIO SCI JI Photochem. Photobiol. Sci. PY 2015 VL 14 IS 8 BP 1492 EP 1509 DI 10.1039/c4pp00455h PG 18 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA CN8YM UT WOS:000358732000012 PM 26062987 ER PT J AU Staudt, G Camann, W AF Staudt, Genevieve Camann, William TI Successful Pregnancy and Delivery in a Patient with Carney Complex: Implications for Anesthesiologists SO A & A CASE REPORTS LA English DT Article ID CARDIAC MYXOMA; CORTICOSTEROIDS AB Carney complex is an autosomal dominant condition with widespread manifestations, including cardiac myxomas, nerve sheath tumors, and endocrinopathies. Although often associated with infertility, there are several reports of successful pregnancies in patients with Carney complex. However, none of the previous reports describe anesthetic considerations. Herein, we present a patient with Carney complex who successfully delivered vaginally with labor epidural analgesia. C1 [Staudt, Genevieve] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Camann, William] Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. RP Staudt, G (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Gray Bigelow 444,55 Fruit St, Boston, MA 02114 USA. EM gstaudt@partners.org NR 16 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2325-7237 J9 A A CASE REP JI A A Case Rep. PD JAN 1 PY 2015 VL 4 IS 1 BP 12 EP 13 DI 10.1213/XAA.0000000000000106 PG 2 WC Anesthesiology SC Anesthesiology GA CM2GI UT WOS:000357497500005 PM 25612273 ER PT J AU Abreo, AP Herzog, CA Kutner, NG Lea, J Johansen, KL AF Abreo, Adrian P. Herzog, Charles A. Kutner, Nancy G. Lea, Janice Johansen, Kirsten L. TI Estimated Pulmonary Artery Systolic Pressure and Self-Reported Physical Function in Patients on Hemodialysis SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Physical function; End-stage renal disease; Echocardiography; Volume status ID QUALITY-OF-LIFE; FREQUENT HEMODIALYSIS; DIALYSIS PATIENTS; KIDNEY-DISEASE; HEART-FAILURE; RISK-FACTORS; HYPERTENSION; HEALTH; EPIDEMIOLOGY; ASSOCIATION AB Background/Aims: Patients on chronic hemodialysis have a high prevalence of heart disease and poor self-reported physical function. The association between structural heart disease and self-reported physical function in patients on hemodialysis is unknown. Methods: We studied the association between elevated pulmonary artery systolic pressure (PASP) and self-reported physical function in ESRD in 253 patients in the USRDS ACTIVE/ADIPOSE study between 2009 and 2011. We used multivariate linear regression with PASP obtained from clinical echocardiogram reports as the primary predictor and the Physical Function (PF) subscale of the SF-36 as the primary outcome. To determine whether associations between PASP and PF were driven by fluid overload or left ventricular hypertrophy, we assessed whether PASP was associated with bioimpedance spectroscopy (BIS)-derived extracellular water (ECW) and with left ventricular posterior wall thickness. Results: In a multivariable model, each 10 mm Hg higher PASP was associated with a 3.32-point lower PF score (95% CI-5.95, -0.68). In a multivariable model that included BIS estimates, both left ventricular posterior wall thickness (LVPW, per 5 mm) and ECW were associated with a higher PASP (LVPW 4.21 mm Hg, 95% 0.38-8.04; ECW 1.12 mm Hg per liter, 95% CI 0.07-2.18). Higher LVPW and ECW were independently associated with a lower PF score. Conclusion: Left ventricular hypertrophy and elevated pulmonary pressure are associated with worse self-reported physical function in patients on hemodialysis. The role of chronic volume overload on PASP and PF score should be evaluated in a prospective manner. (C) 2015 S. Karger AG, Basel C1 [Abreo, Adrian P.] Univ Cincinnati, Coll Med, Div Nephrol, Cincinnati, OH 45267 USA. [Abreo, Adrian P.] Cincinnati VA Med Ctr, Nephrol Sect, Cincinnati, OH USA. [Herzog, Charles A.] Hennepin Cty Med Ctr, Div Cardiol, Minneapolis, MN 55415 USA. [Herzog, Charles A.] Univ Minnesota, Minneapolis, MN USA. [Kutner, Nancy G.] Emory Univ, Sch Med, Dept Rehabil Med, Atlanta, GA USA. [Lea, Janice] Emory Univ, Sch Med, Div Nephrol, Atlanta, GA USA. [Johansen, Kirsten L.] San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Johansen, Kirsten L.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Abreo, AP (reprint author), Univ Cincinnati, Coll Med, 231 Albert Sabin Way,MSB 6252, Cincinnati, OH 45267 USA. EM adrian.abreo@uc.edu FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [N01-DK-7-0005, N01-DK-7-5004]; [K24DK085153] FX This work was supported through contracts N01-DK-7-0005 and N01-DK-7-5004 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and a K24DK085153 grant. NR 37 TC 0 Z9 0 U1 2 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 EI 1421-9670 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2015 VL 41 IS 4-5 BP 313 EP 319 DI 10.1159/000431334 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA CN6AF UT WOS:000358515000009 PM 26089100 ER PT S AU Wahlqvist, ML Krawetz, SA Rizzo, NS Dominguez-Bello, MG Szymanski, LM Barkin, S Yatkine, A Waterland, RA Mennella, JA Desai, M Ross, MG Krebs, NF Young, BE Wardle, J Wrann, CD Kral, JG AF Wahlqvist, Mark L. Krawetz, Stephen A. Rizzo, Nico S. Dominguez-Bello, Maria Gloria Szymanski, Linda M. Barkin, Shari Yatkine, Ann Waterland, Robert A. Mennella, Julie A. Desai, Mina Ross, Michael G. Krebs, Nancy F. Young, Bridget E. Wardle, Jane Wrann, Christiane D. Kral, John G. GP New York Acad Sci TI Early-life influences on obesity: from preconception to adolescence SO ANNALS REPORTS, VOL 1347 SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE obesity; diabesity; nutrition; econutritional; epigenetics; microbiome; exercise; taste preferences; breast feeding ID EATING BEHAVIOR QUESTIONNAIRE; PHYSICAL-ACTIVITY; HELICOBACTER-PYLORI; CESAREAN-SECTION; CHILDHOOD OBESITY; DNA METHYLATION; ALLERGIC-ASTHMA; GUT MICROBIOME; UNITED-STATES; PUBLIC-HEALTH AB The double burden of under- and overnutrition profoundly affects human health globally. According to the World Health Organization, obesity and diabetes rates have almost doubled worldwide since 1980, and, in 2011, more than 40 million children under 5 years of age were overweight. Ecologic factors, parental genetics and fitness, and the intrauterine environment significantly influence the likelihood of offspring developing the dysmetabolic diathesis of obesity. This report examines the effects of these factors, including preconception, intrauterine and postnatal energy balance affecting programming of transgenerational transmission, and development of chronic diseases later in life- in particular, diabesity and its comorbidities. C1 [Wahlqvist, Mark L.] Zhejiang Univ, Hangzhou 310003, Zhejiang, Peoples R China. [Krawetz, Stephen A.] Wayne State Univ, CS Mott Ctr Human Growth & Dev, Detroit, MI USA. [Krawetz, Stephen A.] Wayne State Univ, Dept Obstet & Gynecol, Ctr Mol Med & Genet, Detroit, MI USA. [Rizzo, Nico S.] Loma Linda Univ, Sch Publ Hlth, Ctr Community Resilience, Loma Linda, CA 92350 USA. [Rizzo, Nico S.] Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden. [Dominguez-Bello, Maria Gloria] NYU, Sch Med, New York, NY USA. [Szymanski, Linda M.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Barkin, Shari; Yatkine, Ann] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Waterland, Robert A.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Waterland, Robert A.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Waterland, Robert A.] ARS, USDA, Childrens Nutr Res Ctr, Houston, TX USA. [Mennella, Julie A.] Monell Chem Senses Ctr, Philadelphia, PA 19104 USA. [Desai, Mina; Ross, Michael G.] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. [Krebs, Nancy F.; Young, Bridget E.] Univ Colorado, Sch Med, Aurora, CO USA. [Wardle, Jane] UCL, Dept Epidemiol & Publ Hlth, London, England. [Wrann, Christiane D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Wrann, Christiane D.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. [Kral, John G.] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. RP Kral, JG (reprint author), Suny Downstate Med Ctr, Dept Surg, 450 Clarkson Ave,Box 40, Brooklyn, NY 11203 USA. EM jkral@downstate.edu OI Mennella, Julie/0000-0002-8855-0204 FU Cancer Research UK [14133]; NICHD NIH HHS [HD072307, HD37119, R01 HD037119, R01 HD072307]; NIDCD NIH HHS [DC011287, R01 DC011287]; NIDDK NIH HHS [R01 DK031405, DK31405, DK90861, R37 DK031405, RC4 DK090861]; NINDS NIH HHS [K99 NS087096, NS087096] NR 105 TC 7 Z9 7 U1 8 U2 37 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 2015 VL 1347 BP 1 EP 28 DI 10.1111/nyas.12778 PG 28 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BD2HT UT WOS:000358763200001 PM 26037603 ER PT J AU Hill, AJ Tirumani, SH Rosenthal, MH Shinagare, AB Carrasco, RD Munshi, NC Ramaiya, NH Howard, SA AF Hill, A. J. Tirumani, S. H. Rosenthal, M. H. Shinagare, A. B. Carrasco, R. D. Munshi, N. C. Ramaiya, N. H. Howard, S. A. TI Multimodality imaging and clinical features in Castleman disease: single institute experience in 30 patients SO BRITISH JOURNAL OF RADIOLOGY LA English DT Article ID LYMPH-NODE HYPERPLASIA; PLASMA-CELL TYPES; SPECTRUM; ABDOMEN; PET AB Objective: To analyse imaging features of subtypes of Castleman disease (CD), emphasizing differentiating features from lymphoma. Methods: Institutional review board-approved, Health Insurance Portability and Accountability Act compliant, retrospective study examined 30 patients with CD. 30 patients (females, 20; mean age, 46 years; range, 22-87 years) with histopathologically confirmed CD and pre-treatment imaging formed the analytic cohort. Imaging at presentation in all patients [CT, 30; positron emission tomography (PET)/CT, 5; MR, 4; ultrasound, 3] and subsequent imaging in three cases that developed lymphoma was reviewed by two radiologists in consensus. Results: Subtypes: hyaline-vascular (n=18); multicentric not otherwise specified (NOS) (n=6); human herpesvirus 8 associated (n=2); mixed unicentric (n=2); pure plasma-cell variant (n=1); and unicentric NOS (n=1). Distribution: unicentric (n=17); and multicentric (n=13). Nodal sites-unicentric: 13 thoracic, 3 abdominal and 1 cervical; multicentric: 9 abdominal, 8 thoracic, 6 cervical, 5 inguinal, 4 axillary and 4 supraclavicular. On CT, differentiating features from lymphoma were calcification (n=8; 26.7%) and heterogeneous enhancement (n=5; 19.2%). No association between CD subtype, degree or enhancement pattern, or calcification was noted. On PET/CT (n=5), nodes were typically fluorine-18 fludeoxyglucose avid (n=4). On ultrasound (n=3), nodes were hypoechoic, homogeneous with posterior acoustic enhancement. On MR (n=4), nodes were hypointense (n=2) to isointense (n=2) on T1 weighted images and isointense (n=1) to hyperintense (n=3) on T2 weighted images. All (n=4) demonstrated homogeneous enhancement. Three cases developed non-Hodgkin's lymphoma, two of the three had larger spleens, and these cases had effusions/ascites. Conclusion: CD can be unicentric or multicentric and involve nodes above and below the diaphragm. Patients with CD can develop lymphoma. Advances in knowledge: Assessing individual risk of developing lymphoma in patients with CD is difficult, although the findings of splenomegaly, pleural effusion and ascites may be suggestive. C1 [Hill, A. J.; Tirumani, S. H.; Rosenthal, M. H.; Shinagare, A. B.; Ramaiya, N. H.; Howard, S. A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Tirumani, S. H.; Rosenthal, M. H.; Shinagare, A. B.; Ramaiya, N. H.; Howard, S. A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Carrasco, R. D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. [Munshi, N. C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Hematol Oncol, Boston, MA 02115 USA. RP Hill, AJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. EM hillaj1@gmail.com FU NCI NIH HHS [P50 CA100707] NR 20 TC 3 Z9 3 U1 0 U2 4 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 EI 1748-880X J9 BRIT J RADIOL JI Br. J. Radiol. PY 2015 VL 88 IS 1049 AR 20140670 DI 10.1259/bjr.20140670 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN6GX UT WOS:000358533600008 PM 25710283 ER PT J AU Kooy, HM Grassberger, C AF Kooy, H. M. Grassberger, C. TI Intensity modulated proton therapy SO BRITISH JOURNAL OF RADIOLOGY LA English DT Review ID CONFORMAL RADIATION-THERAPY; RELATIVE BIOLOGICAL EFFECTIVENESS; WILL SIGNIFICANTLY REDUCE; CARLO DOSE CALCULATION; PROMPT GAMMA-RAYS; RANGE UNCERTAINTIES; BEAM THERAPY; COMPUTED-TOMOGRAPHY; OPTIMIZATION; RADIOTHERAPY AB Intensity modulated proton therapy (IMPT) implies the electromagnetic spatial control of well-circumscribed "pencil beams" of protons of variable energy and intensity. Proton pencil beams take advantage of the charged-particle Bragg peak-the characteristic peak of dose at the end of range-combined with the modulation of pencil beam variables to create target-local modulations in dose that achieves the dose objectives. IMPT improves on X-ray intensity modulated beams (intensity modulated radiotherapy or volumetric modulated arc therapy) with dose modulation along the beam axis as well as lateral, in-field, dose modulation. The clinical practice of IMPT further improves the healthy tissue vs target dose differential in comparison with X-rays and thus allows increased target dose with dose reduction elsewhere. In addition, heavy-charged-particle beams allow for the modulation of biological effects, which is of active interest in combination with dose "painting" within a target. The clinical utilization of IMPT is actively pursued but technical, physical and clinical questions remain. Technical questions pertain to control processes for manipulating pencil beams from the creation of the proton beam to delivery within the patient within the accuracy requirement. Physical questions pertain to the interplay between the proton penetration and variations between planned and actual patient anatomical representation and the intrinsic uncertainty in tissue stopping powers (the measure of energy loss per unit distance). Clinical questions remain concerning the impact and management of the technical and physical questions within the context of the daily treatment delivery, the clinical benefit of IMPT and the biological response differential compared with X-rays against which clinical benefit will be judged. It is expected that IMPT will replace other modes of proton field delivery. Proton radiotherapy, since its first practice 50 years ago, always required the highest level of accuracy and pioneered volumetric treatment planning and imaging at a level of quality now standard in X-ray therapy. IMPT requires not only the highest precision tools but also the highest level of system integration of the services required to deliver high-precision radiotherapy. C1 [Kooy, H. M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kooy, HM (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM hkooy@mgh.harvard.edu NR 66 TC 4 Z9 4 U1 2 U2 8 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 EI 1748-880X J9 BRIT J RADIOL JI Br. J. Radiol. PY 2015 VL 88 IS 1051 AR 20150195 DI 10.1259/bjr.20150195 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN6HN UT WOS:000358535400029 PM 26084352 ER PT J AU Paganetti, H El Fakhri, G AF Paganetti, H. El Fakhri, G. TI Monitoring proton therapy with PET SO BRITISH JOURNAL OF RADIOLOGY LA English DT Editorial Material ID BEAM RANGE VERIFICATION; POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO VERIFICATION; RADIATION-THERAPY; PROMPT GAMMA; IRRADIATION; DELIVERY; PATIENT; IMAGES; ROOM AB Protons are being used in radiation therapy because of typically better dose conformity and reduced total energy deposited in the patient as compared with photon techniques. Both aspects are related to the finite range of a proton beam. The finite range also allows advanced dose shaping. These benefits can only be fully utilized if the end of range can be predicted accurately in the patient. The prediction of the range in tissue is associated with considerable uncertainties owing to imaging, patient set-up, beam delivery, interfractional changes in patient anatomy and dose calculation. Consequently, a significant range (of the order of several millimetres) is added to the prescribed range in order to ensure tumour coverage. Thus, reducing range uncertainties would allow a reduction of the treatment volume and reduce dose to potential organs at risk. C1 [Paganetti, H.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Paganetti, H.; El Fakhri, G.] Harvard Univ, Sch Med, Boston, MA USA. [El Fakhri, G.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Paganetti, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM hpaganetti@mgh.harvard.edu NR 25 TC 2 Z9 2 U1 2 U2 5 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 EI 1748-880X J9 BRIT J RADIOL JI Br. J. Radiol. PY 2015 VL 88 IS 1051 AR 20150173 DI 10.1259/bjr.20150173 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA CN6HN UT WOS:000358535400028 PM 25989699 ER PT S AU Cacciatore, S Loda, M AF Cacciatore, Stefano Loda, Massimo BE Carini, C TI Innovation in metabolomics to improve personalized healthcare SO COMPANION DIAGNOSTICS: FROM BIOMARKER IDENTIFICATION TO MARKET ENTRY SE Annals of the New York Academy of Sciences LA English DT Article; Book Chapter DE metabolomics; prostate cancer; FFPE; fatty acid; oncogene ID FATTY-ACID SYNTHASE; PROSTATE-CANCER PROGRESSION; HUMAN SERUM; IN-VIVO; METABOLISM; CELLS; SPECTROSCOPY; SARCOSINE; CITRATE; TISSUE AB Metabolomics is the systemic study of all small molecules (metabolites) and their concentration as affected by pathological and physiological alterations or environmental or other factors. Metabolic alterations represent a "window" on the complex interactions between genetic expression, enzyme activity, and metabolic reactions. Techniques, including nuclear magnetic resonance spectroscopy, mass spectrometry, Fourier-transform infrared, and Raman spectroscopy, have led to significant advances in metabolomics. The field is shifting from feasibility studies to biological and clinical applications. Fields of application range from cancer biology to stem cell research and assessment of xenobiotics and drugs in tissues and single cells. Cross-validation across high-throughput platforms has allowed findings from expression profiling to be confirmed with metabolomics. Specific genetic alterations appear to drive unique metabolic programs. These, in turn, can be used as biomarkers of genetic subtypes of prostate cancer or as discovery tools for therapeutic targeting of metabolic enzymes. Thus, metabolites in blood may serve as biomarkers of tumor state, including inferring driving oncogenes. Novel applications such as these suggest that metabolic profiling may be utilized in refining personalized medicine. C1 [Cacciatore, Stefano; Loda, Massimo] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Loda, Massimo] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Loda, Massimo] Broad Inst, Cambridge, MA USA. [Loda, Massimo] Kings Coll London, Div Canc Studies, London WC2R 2LS, England. RP Loda, M (reprint author), Dana Farber Canc Inst, D1536,450 Longwood Ave, Boston, MA 02115 USA. EM massimo_loda@dfci.harvard.edu OI Cacciatore, Stefano/0000-0001-7052-7156 FU NCI NIH HHS [2R01CA131945, P50 CA090381, P50 CA90381, R01 CA131945] NR 45 TC 11 Z9 11 U1 2 U2 12 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 2015 VL 1346 BP 57 EP 62 DI 10.1111/nyas.12775 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA BD2NC UT WOS:000358920200007 PM 26014591 ER PT J AU Buckley, EM Patel, SD Miller, BF Franceschini, MA Vannucci, SJ AF Buckley, Erin M. Patel, Shyama D. Miller, Benjamin F. Franceschini, Maria Angela Vannucci, Susan J. TI In vivo Monitoring of Cerebral Hemodynamics in the Immature Rat: Effects of Hypoxia-Ischemia and Hypothermia SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE Cerebral blood flow; Hypoxic-ischemic encephalopathy; Therapeutic hypothermia; Diffuse correlation spectroscopy ID DIFFUSE CORRELATION SPECTROSCOPY; NEAR-INFRARED SPECTROSCOPY; MAGNETIC-RESONANCE-SPECTROSCOPY; BLOOD-FLOW; THERAPEUTIC HYPOTHERMIA; BRAIN-DAMAGE; NEUROPROTECTIVE MECHANISMS; OXYGEN-METABOLISM; NEURONAL RESCUE; ENCEPHALOPATHY AB Background: Neonatal hypoxic-ischemic (HI) encephalopathy occurs in 1-4 per 1,000 live term births and can cause devastating neurodevelopmental disabilities. Currently, therapeutic hypothermia (TH) is the only treatment with proven efficacy. Since TH is associated with decreased cerebral metabolism and cerebral blood flow (CBF), it is important to assess CBF at the bedside. Diffuse correlation spectroscopy (DCS) has emerged as a promising optical modality to non-invasively assess an index of CBF (CBFi) in both humans and animals. In this initial descriptive study, we employ DCS to monitor the evolution of CBFi following HI with or without TH in immature rats. We investigate potential relationships between CBF and subsequent cerebral damage. Methods: HI was induced on postnatal day 10 or 11 rat pups by right common carotid artery ligation followed by 60-70 min hypoxia (8% oxygen). After HI, the pups recovered for 4 h under hypothermia (HI-TH group, n = 23) or normothermia (HI-N group, n = 23). Bilateral measurements of hemispheric CBFi were made with DCS in unanesthetized animals at baseline, before HI, and 0, 1, 2, 3, 4, 5, and 24 h after HI. The animals were sacrificed at either 1 or 4 weeks, and brain injury was scored on an ordinal scale of 0-5 (0 = no injury). Results: Carotid ligation caused moderate bilateral decreases in CBFi. Following HI, an initial hyperemia was observed that was more prominent in the contralateral hemisphere. After initiation of TH, CBFi dropped significantly below baseline levels and remained reduced for the duration of TH. In contrast, CBFi in the HI-N group was not significantly decreased from baseline levels. Reductions in CBFi after 4 h of TH were not associated with reduced damage at 1 or 4 weeks. However, elevated ipsilateral CBFi and ipsilateral-to-contralateral CBFi ratios at 24 h were associated with worse outcome at 1 week after HI. Conclusions: Both HI and TH alter CBFi, with significant differences in CBFi between hypothermic and normothermic groups after HI. CBFi may be a useful biomarker of subsequent cerebral damage. (C) 2015 S. Karger AG, Basel C1 [Buckley, Erin M.; Miller, Benjamin F.; Franceschini, Maria Angela] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Patel, Shyama D.; Vannucci, Susan J.] Weill Cornell Med Coll, Dept Pediat Newborn Med, New York, NY USA. RP Buckley, EM (reprint author), Massachusetts Gen Hosp, 13th St,Bldg 149, Charlestown, MA 02129 USA. EM ebuckle2@gmail.com FU National Institutes of Health [R01-EB001954, R21NS083425]; Fondation Leducq Transatlantic Network for Neonatal Stroke; MGH ECOR Fund FX We would like to thank Dr. P. Ellen Grant for support and helpful discussions, Dr. Ivy Lin for help with optical probe construction, Alexandria Hutton for expert technical assistance, Dr. Stefan Carp for assistance with DCS acquisition software, and Dr. Robert C. Vannucci for helpful discussion and critical review of the manuscript. We would also like to gratefully acknowledge support from the National Institutes of Health through grant No. R01-EB001954 (M.A. Franceschini, principal investigator) and R21NS083425 (S.J. Vannucci, principal investigator), the Fondation Leducq Transatlantic Network for Neonatal Stroke (S.J. Vannucci) and the MGH ECOR Fund for Medical Discovery Postdoctoral Fellowship Award (E.M. Buckley, principal investigator). NR 40 TC 3 Z9 3 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 EI 1421-9859 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PY 2015 VL 37 IS 4-5 BP 407 EP 416 DI 10.1159/000381704 PG 10 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA CN6BN UT WOS:000358518500012 PM 26021410 ER PT J AU Francis, SA Asnani, A Neilan, T Scherrer-Crosbie, M AF Francis, Sanjeev A. Asnani, Aarti Neilan, Tomas Scherrer-Crosbie, Marielle TI Optimizing cardio-oncology programs for cancer patients SO FUTURE ONCOLOGY LA English DT Editorial Material DE anthracycline; cardio-oncology; chemotherapy-induced cardiomyopathy; cardiotoxicity; cardiovascular screening; radiation-associated heart disease; survivorship ID CARDIOVASCULAR COMPLICATIONS; RETROSPECTIVE ANALYSIS; EUROPEAN ASSOCIATION; EXPERT CONSENSUS; AMERICAN SOCIETY; BREAST-CANCER; HEART-FAILURE; THERAPY; CHEMOTHERAPY; ECHOCARDIOGRAPHY C1 [Francis, Sanjeev A.; Asnani, Aarti; Neilan, Tomas; Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Div Cardiol, Cardiooncol Program, Boston, MA 02114 USA. RP Francis, SA (reprint author), Massachusetts Gen Hosp, Div Cardiol, Cardiooncol Program, Boston, MA 02114 USA. EM safrancis@partners.org NR 20 TC 1 Z9 1 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 EI 1744-8301 J9 FUTURE ONCOL JI Future Oncol. PY 2015 VL 11 IS 14 BP 2011 EP 2015 DI 10.2217/fon.15.128 PG 5 WC Oncology SC Oncology GA CN3FW UT WOS:000358311800006 PM 26198828 ER PT J AU Adams, ZW Danielson, CK Sumner, JA McCauley, JL Cohen, JR Ruggiero, KJ AF Adams, Zachary W. Danielson, Carla Kmett Sumner, Jennifer A. McCauley, Jenna L. Cohen, Joseph R. Ruggiero, Kenneth J. TI Comorbidity of PTSD, Major Depression, and Substance Use Disorder Among Adolescent Victims of the Spring 2011 Tornadoes in Alabama and Joplin, Missouri SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; RISK; TRAUMA; INTERVENTION; PREVALENCE; SYMPTOMS; YOUTH; MOOD AB Objective: The purpose of this study was twofold: (1) to estimate the prevalence of comorbid posttraumatic stress disorder (PTSD), major depressive episode (MDE), and substance use disorder (SUD); and (2) to identify risk factors for patterns of comorbidity among adolescents affected by disasters. Method: A population-based sample of 2,000 adolescents (51% female; 71% Caucasian, 26% African American) aged 12 to 17 years (M = 14.5, SD = 1.7) and their parents was recruited from communities affected by the spring 2011 tornadoes in Alabama and Joplin, Missouri. Participants completed structured telephone interviews assessing demographic characteristics, impact of disaster, prior trauma history, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), symptoms of posttraumatic stress disorder (PTSD) and major depressive episode (MDE), and substance use disorder (SUD) symptoms. Prevalence estimates were calculated for PTSD + MDE, PTSD + SUD, MDE + SUD, and PTSD + MDE + SUD. Hierarchical logistic regression was used to identify risk factors for each comorbidity profile. Results: Overall prevalence since the tornado was 3.7% for PTSD + MDE, 1.1% for PTSD + SUD, 1.0% for MDE + SUD, and 0.7% for PTSD + MDE + SUD. Girls were significantly more likely than boys to meet criteria for PTSD + MDE and MDE + SUD (ps<.05). Female gender, exposure to prior traumatic events, and persistent loss of services were significant risk factors for patterns of comorbidity. Parental injury was associated with elevated risk for PTSD + MDE. Adolescents should be evaluated for comorbid problems, including SUD, following disasters so that appropriate referrals to evidence-based treatments can be made. Conclusions: Results suggest that screening procedures to identify adolescents at risk for comorbid disorders should assess demographic characteristics (gender), impact of the disaster on the family, and adolescents' prior history of stressful events. C1 [Adams, Zachary W.; Danielson, Carla Kmett; Cohen, Joseph R.] Med Univ S Carolina, Natl Crime Victims Res & Treatment Ctr, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Sumner, Jennifer A.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. [McCauley, Jenna L.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Clin Neurosci Div, Charleston, SC 29425 USA. [Ruggiero, Kenneth J.] Med Univ S Carolina, Coll Nursing, Charleston, SC 29425 USA. [Ruggiero, Kenneth J.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Adams, ZW (reprint author), Med Univ S Carolina, Natl Crime Victims Res & Treatment Ctr, 67 President St, Charleston, SC 29425 USA. EM adamsz@musc.edu FU National Institute of Mental Health [R01-MH81056, T32-MH18869]; National Institute on Drug Abuse [K12-DA031794, R01-DA031285] FX This research was supported by National Institute of Mental Health grants R01-MH81056 and T32-MH18869 and National Institute on Drug Abuse grants K12-DA031794 and R01-DA031285. The authors have no other conflicts to disclose. NR 39 TC 2 Z9 2 U1 2 U2 9 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 370 SEVENTH AVE, SUITE 1200, NEW YORK, NY 10001-1020 USA SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PY 2015 VL 78 IS 2 BP 170 EP 185 DI 10.1080/00332747.2015.1051448 PG 16 WC Psychiatry SC Psychiatry GA CN5BT UT WOS:000358445200008 PM 26168094 ER PT S AU Heinzen, EL Neale, BM Traynelis, SF Allen, AS Goldstein, DB AF Heinzen, Erin L. Neale, Benjamin M. Traynelis, Stephen F. Allen, Andrew S. Goldstein, David B. BE Hyman, SE TI The Genetics of Neuropsychiatric Diseases: Looking In and Beyond the Exome SO ANNUAL REVIEW OF NEUROSCIENCE, VOL 38 SE Annual Review of Neuroscience LA English DT Review; Book Chapter DE neuropsychiatric disease; next-generation sequencing; gene discovery ID DE-NOVO MUTATIONS; INFANTILE EPILEPTIC ENCEPHALOPATHY; RARE-VARIANT ASSOCIATION; IDIOPATHIC GENERALIZED EPILEPSY; MIGRATING PARTIAL SEIZURES; AUTISM SPECTRUM DISORDERS; SEVERE MYOCLONIC EPILEPSY; INTELLECTUAL DISABILITY; SODIUM-CHANNEL; NEURODEVELOPMENTAL PHENOTYPES AB Next-generation sequencing, which allows genome-wide detection of rare and de novo mutations, is transforming neuropsychiatric disease genetics through identifying on an unprecedented scale genes and protein-coding mutations that confer risk. Although understanding how regulatory variants influence risk remains a challenge, we are likely transitioning into a phase of neuropsychiatric disease genetics in which the rate-limiting step may no longer be gene discovery. Instead, the future will concentrate more on the biological and clinical translation of the torrent of specific risk mutations identified through next-generation sequencing. Here, we review the recent progress that resulted specifically from exome sequencing and emphasize the need for rigorous statistical evaluation of the expanding data sets, as well as expanded functional analysis of implicated proteins and mutations. Then, we introduce some of the expected opportunities and challenges investigators face when moving beyond the exome. Finally, we briefly highlight the challenge of deriving translational benefit from the progress in genetics. C1 [Heinzen, Erin L.; Goldstein, David B.] Columbia Univ, Inst Genom Med, New York, NY 10032 USA. [Heinzen, Erin L.] Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA. [Goldstein, David B.] Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA. [Neale, Benjamin M.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Dept Med, Boston, MA 02114 USA. [Neale, Benjamin M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Neale, Benjamin M.] Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Neale, Benjamin M.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Traynelis, Stephen F.] Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA. [Allen, Andrew S.] Duke Univ, Dept Biostat & Bioinformat, Durham, NC 27710 USA. RP Heinzen, EL (reprint author), Columbia Univ, Inst Genom Med, New York, NY 10032 USA. EM eh2682@cumc.columbia.edu; dbgoldstein@cumc.columbia.edu NR 111 TC 4 Z9 4 U1 1 U2 7 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0147-006X BN 978-0-8243-2438-4 J9 ANNU REV NEUROSCI JI Annu. Rev. Neurosci. PY 2015 VL 38 BP 47 EP 68 DI 10.1146/annurev-neuro-071714-034136 PG 22 WC Neurosciences SC Neurosciences & Neurology GA BD1XD UT WOS:000358485000003 PM 25840007 ER PT J AU Polidori, MC Calistri, V Mainero, C Tinelli, E Aceti, A Pontico, M Tardioli, S Santini, M Fiorelli, M Panico, MA Speziale, F Caramia, MD Schulz, RJ Caramia, F AF Polidori, M. C. Calistri, V. Mainero, C. Tinelli, E. Aceti, A. Pontico, M. Tardioli, S. Santini, M. Fiorelli, M. Panico, M. A. Speziale, F. Caramia, M. D. Schulz, R. -J. Caramia, F. TI Differential Influence of Carotid Stenosis and White Matter Disease on Motor and Cognitive Activation SO CURRENT ALZHEIMER RESEARCH LA English DT Article DE Cognitive impairment; healthy ageing; intima-media thickness; vascular diseases; vitamins ID INTIMA-MEDIA THICKNESS; VASCULAR RISK-FACTORS; ALZHEIMERS-DISEASE; FOLLOW-UP; DEMENTIA; ATHEROSCLEROSIS; BRAIN; ARTERY; HYPERINTENSITIES; ASSOCIATION AB Background: Cognitive and motor performance can be supported, especially in older subjects, by different types of brain activations, which can be accurately studied by functional magnetic resonance imaging (fMRI). Vascular risk factors (VRFs) are extremely important in the development of cognitive impairment, but few studies have focused on the fMRI cortical activation characteristics of healthy subjects with and without silent cerebrovascular disease including white matter hyperintensities (WMH) and carotid stenosis (CS) performing cognitive tasks. Methods: Thirty-five volunteers with and without asymptomatic unilateral carotid stenosis above 70% and variable degrees of WMH underwent performance of a simple motor and cognitive task during an fMRI session. Results: While the performance of the motor task resulted in a cortical activation dependent of age but not of WMH and carotid stenosis, performance of the cognitive task was accompanied by a significantly increased activation independently correlated with age, presence of WMH as well as of carotid stenosis. Conclusions: in this study, cognitive domains regulating attention and working memory appear to be activated with a pattern influenced by the presence of carotid stenosis as well as by white matter hyperintensities. The impairment of these cognitive abilities is of high relevance in Alzheimer's disease pathology. The fMRI pattern shown in patients with asymptomatic but significant carotid stenosis might be related to chronic cerebrovascular hypoperfusion, a critical pathophysiological mechanisms in AD. In these patients, carotid endoarterectomy should be considered also for AD prevention and might be recommended. C1 [Polidori, M. C.] St Marienhosp Cologne, Dept Geriatr, Cologne, Germany. [Polidori, M. C.] Univ Cologne, Fac Med, D-50931 Cologne, Germany. [Calistri, V.; Tinelli, E.; Aceti, A.; Pontico, M.; Tardioli, S.; Santini, M.; Fiorelli, M.; Caramia, F.] Univ Roma La Sapienza, Dipartimento Neurol & Psichiatria, I-00185 Rome, Italy. [Mainero, C.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Panico, M. A.; Speziale, F.] Univ Roma La Sapienza, Policlin Umberto I, Dept Surg Paride Stefanini, Vasc & Endovasc Surg Div, I-00185 Rome, Italy. [Caramia, M. D.] Univ Roma Tor Vergata, Dept Publ Hlth, Rome, Italy. [Schulz, R. -J.] St Marien Hosp, Dept Geriatr Med, Cologne, Germany. RP Caramia, F (reprint author), Univ Roma La Sapienza, Dipartimento Neurol & Psichiatria, Viale Univ 30, I-00185 Rome, Italy. EM francesca.caramia@uniroma1.it FU MPI_AGE project - European Commission under the European Commission Public Health Programme FX MCP gratefully acknowledges the support of the MPI_AGE project funded by the European Commission under the European Commission Public Health Programme 2008-2013. The contents of this work are the sole responsibility of the author and can under no circumstances be regarded as reflecting the position of the European Union. NR 43 TC 1 Z9 1 U1 0 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 EI 1875-5828 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PY 2015 VL 12 IS 6 BP 585 EP 591 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CN3CZ UT WOS:000358302800010 PM 26238813 ER PT J AU Tang, XC Marasco, WA AF Tang, Xian-Chun Marasco, Wayne A. TI Human neutralizing antibodies against MERS coronavirus: implications for future immunotherapy SO IMMUNOTHERAPY LA English DT Editorial Material DE animal model; biodefense; emerging pathogen; human monoclonal antibodies; humoral immunity; IGHV1-69; MERS-CoV; passive immunotherapy; spike protein; zoonosis ID EAST RESPIRATORY SYNDROME; RHESUS MACAQUES; COV; INFECTION C1 [Tang, Xian-Chun; Marasco, Wayne A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. RP Marasco, WA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02215 USA. EM wayne_marasco@dfci.harvard.edu FU NIAID NIH HHS [R01AI085524, R01 AI085524] NR 17 TC 0 Z9 0 U1 1 U2 3 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1750-743X EI 1750-7448 J9 IMMUNOTHERAPY-UK JI Immunotherapy PY 2015 VL 7 IS 6 BP 591 EP 594 DI 10.2217/IMT.15.33 PG 4 WC Immunology SC Immunology GA CN3AT UT WOS:000358296300002 PM 26098703 ER PT J AU Neagu, MR Reardon, DA AF Neagu, Martha R. Reardon, David A. TI Rindopepimut vaccine and bevacizumab combination therapy: improving survival rates in relapsed glioblastoma patients? SO IMMUNOTHERAPY LA English DT Editorial Material DE bevacizumab; epidermal growth factor receptor variant III; glioblastoma; rindopepimut; vaccine ID NEWLY-DIAGNOSED GLIOBLASTOMA; GROWTH-FACTOR RECEPTOR; RANDOMIZED PHASE-III; PEPTIDE VACCINATION; TRIAL; TEMOZOLOMIDE; MULTIFORME; IMMUNOTHERAPY; RADIOTHERAPY; CANCER C1 [Neagu, Martha R.; Reardon, David A.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02115 USA. RP Reardon, DA (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, G4200,44 Binney St, Boston, MA 02115 USA. EM david_reardon@dfci.harvard.edu NR 20 TC 4 Z9 4 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1750-743X EI 1750-7448 J9 IMMUNOTHERAPY-UK JI Immunotherapy PY 2015 VL 7 IS 6 BP 603 EP 606 DI 10.2217/IMT.15.39 PG 4 WC Immunology SC Immunology GA CN3AT UT WOS:000358296300006 PM 26100271 ER PT S AU Pillai, A Yao, JK AF Pillai, Anilkumar Yao, Jeffrey K. BE DietrichMuszalska, A Chauhan, V Grignon, S TI Antioxidant Interventions in Neuropsychiatric Disorders SO STUDIES ON PSYCHIATRIC DISORDERS SE Oxidative Stress in Applied Basic Research and Clinical Practice LA English DT Article; Book Chapter ID POLYUNSATURATED FATTY-ACIDS; RANDOMIZED CONTROLLED-TRIALS; PLACEBO-CONTROLLED-TRIAL; BLOOD-CELL MEMBRANES; VITAMIN-E TREATMENT; SERUM NITRIC-OXIDE; N-ACETYL CYSTEINE; BIPOLAR DISORDER; TARDIVE-DYSKINESIA; OXIDATIVE STRESS C1 [Pillai, Anilkumar] Georgia Hlth Sci Univ, Dept Psychiat & Hlth Behav, Augusta, GA 30901 USA. [Yao, Jeffrey K.] VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA 15240 USA. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Med, WPIC, Dept Psychiat, Pittsburgh, PA 15213 USA. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15216 USA. RP Yao, JK (reprint author), VA Pittsburgh Healthcare Syst, Med Res Serv, 151 Univ Dr C, Pittsburgh, PA 15240 USA. EM jkyao@pitt.edu NR 119 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2197-7224 BN 978-1-4939-0440-2; 978-1-4939-0439-6 J9 OXID STRESS APPL BAS JI Oxid. Stress Appl. Basic Res. Clin. Pract. PY 2015 BP 505 EP 520 DI 10.1007/978-1-4939-0440-2_25 D2 10.1007/978-1-4939-0440-2 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA BD1YO UT WOS:000358504200026 ER PT J AU Bergman, AA Frankel, RM Hamilton, AB Yano, EM AF Bergman, Alicia A. Frankel, Richard M. Hamilton, Alison B. Yano, Elizabeth M. TI Challenges with Delivering Gender-Specific and Comprehensive Primary Care to Women Veterans SO WOMENS HEALTH ISSUES LA English DT Article ID HEALTH-CARE; SEXUAL TRAUMA; MEDICAL HOME; AFFAIRS; EXPERIENCES; PREFERENCES; CLINICS AB Background: The growing presence of women veterans in Veterans Administration (VA) settings has prompted the need for greater attention to clinical proficiency related to women's health (WH) primary care needs. Instead of making appointments for multiple visits or referring patients to a WH clinic or alternate site for gender-specific care, a comprehensive primary care model now allows for women veteran patients be seen by primary care providers (PCPs) who have WH training/experience and can see patients for both primary and WH care in the context of a single visit. However, little is currently known about the barriers and facilitators WH-PCPs face in using this approach to incorporate gender-specific services into women veterans' primary care services. Methods: We conducted qualitative in-depth interviews with 22 WH-PCPs at one Midwestern VA Medical Center. All participants were members of one of four outpatient primary care clinics within the main medical center, one off-site satellite clinic, or two off-site community-based outpatient clinics. Results: Inductive thematic analysis identified six themes: 1) Time constraints, 2) importance of staff support, 3) necessity of sufficient space and equipment/supplies, 4) perceptions of discomfort among patients with trauma histories, 5) lack of education/training, and 6) challenges with scheduling/logistics. Conclusion: Although adequate staff was a key facilitator, the findings suggest that there may be barriers that undermine the ability of VA WH-PCPs to provide high-quality, comprehensive primary and gender-specific care. The nature of these barriers is multifactorial and multilevel in nature, and may therefore require special policy and practice action. Published by Elsevier Inc. C1 [Bergman, Alicia A.; Frankel, Richard M.] Richard L Roudebush VA Med Ctr, Ctr Hlth Informat & Commun, Dept Vet Affairs, Vet Hlth Adm,Hlth Serv Res & Dev Serv CIN 13 416, Indianapolis, IN USA. [Bergman, Alicia A.; Hamilton, Alison B.; Yano, Elizabeth M.] VA Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Innovat Implementat & Policy, Hlth Serv Res & Dev Serv CIN 13 417, North Hills, CA 91343 USA. [Frankel, Richard M.] Indiana Univ Sch Med, Med, Indianapolis, IN 46202 USA. [Frankel, Richard M.] Indiana Univ Sch Med, Geriatr, Indianapolis, IN 46202 USA. [Yano, Elizabeth M.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA. RP Bergman, AA (reprint author), VA Greater Los Angeles Healthcare Syst, 16111 Plummer St,Bldg 25 Off B-110, North Hills, CA 91343 USA. EM alicia.bergman@va.gov FU Indiana Institute for Medical Research Young Investigator Award (YIA); Department of Veterans Affairs, Veterans Health Administration Health Services Research and Development (HSR&D) Associated Health Fellowship Program; VA HSR&D Senior Research Career Scientist Award [05-195]; VA HSR&D Center of Excellence in Implementing Evidence-Based Practice, Indianapolis, Indiana [HFP 04-148] FX The project reported here was supported by the Indiana Institute for Medical Research Young Investigator Award (YIA) funding (Bergman) and the Department of Veterans Affairs, Veterans Health Administration Health Services Research and Development (HSR&D) Associated Health Fellowship Program (Bergman). Dr. Yano's effort was supported by a VA HSR&D Senior Research Career Scientist Award (Project #05-195). Dr. Frankel's efforts were supported by the VA HSR&D Center of Excellence in Implementing Evidence-Based Practice, Indianapolis, Indiana (HFP 04-148). Portions of this article were presented at the Society for General Internal Medicine Annual Conference, April, 2013, in Denver, Colorado. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs or the United States Government. There are no financial conflicts of interest involving any of the coauthors. NR 28 TC 2 Z9 2 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JAN-FEB PY 2015 VL 25 IS 1 BP 28 EP 34 DI 10.1016/j.whi.2014.10.004 PG 7 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA CN7GN UT WOS:000358602500006 PM 25530547 ER PT J AU Wang, JM Lee, LO Spiro, A AF Wang, Joyce M. Lee, Lewina O. Spiro, Avron, III TI Gender Differences in the Impact of Warfare Exposure on Self-Rated Health SO WOMENS HEALTH ISSUES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; REPORTED PHYSICAL HEALTH; WOMEN VETERANS; MENTAL-HEALTH; FUNCTIONAL IMPAIRMENT; COMBAT EXPOSURE; US MILITARY; WAR; SYMPTOMS; ASSOCIATION AB Background: This study examined gender differences in the impact of warfare exposure on self-reported physical health. Methods: Data are from the 2010 National Survey of Veterans, a nationally representative survey of veterans from multiple eras of service. Regression analyses assessed gender differences in the association between warfare exposure (deployment to a war zone, exposure to casualties) and health status and functional impairment, adjusting for sociodemographics. Findings: Women reported better health status but greater functional impairment than men. Among men, those who experienced casualties only or both casualties and deployment to a war zone had worse health compared with those who experienced neither stressor or deployment to a war zone only. Among women, those who experienced casualties only or both stressors reported worse health than those who experienced war zone only, who did not differ from the unexposed. No association was found between warfare exposure and functional impairment in women; in men, however, those who experienced exposure to casualties or both stressors had greater odds of functional impairment compared with those who experienced war zone only or neither stressor. Conclusions: Exposure to casualties may be more predictive of health than deployment to a war zone, especially for men. We did not find a stronger association between warfare exposure and health for women than men. Given that the expansion of women's military roles has allowed them to serve in direct combat, their degree and scope of warfare exposure is likely to increase in the future. Copyright (C) 2015 by the Jacobs Institute of Women's Health. Published by Elsevier Inc. C1 [Wang, Joyce M.; Lee, Lewina O.; Spiro, Avron, III] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Wang, Joyce M.; Lee, Lewina O.; Spiro, Avron, III] Boston Univ, Sch Publ Hlth, Boston, MA 02130 USA. [Lee, Lewina O.; Spiro, Avron, III] Boston Univ, Sch Med, Boston, MA 02130 USA. [Spiro, Avron, III] Boston Univ, Sch Dent Med, Boston, MA 02130 USA. RP Wang, JM (reprint author), Boston Univ, Sch Publ Hlth, VA Boston Healthcare Syst, 150 S Huntington Ave 151-N, Boston, MA 02130 USA. EM joycemw@bu.edu FU VA Clinical Science Research and Development Service Senior Research Career Scientist Award; National Institutes of Health [R24-AG039343] FX This research was supported by a VA Clinical Science Research and Development Service Senior Research Career Scientist Award and National Institutes of Health grant R24-AG039343. The views expressed in this paper are those of the authors and do not necessarily represent the views of the U.S. Department of Veterans Affairs. NR 44 TC 1 Z9 1 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JAN-FEB PY 2015 VL 25 IS 1 BP 35 EP 41 DI 10.1016/j.whi.2014.09.003 PG 7 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA CN7GN UT WOS:000358602500007 PM 25442366 ER PT J AU Montgomery, AE Dichter, ME Thomasson, AM Fu, XY Roberts, CB AF Montgomery, Ann Elizabeth Dichter, Melissa E. Thomasson, Arwin M. Fu, Xiaoying Roberts, Christopher B. TI Demographic Characteristics Associated with Homelessness and Risk Among Female and Male Veterans Accessing VHA Outpatient Care SO WOMENS HEALTH ISSUES LA English DT Article ID VIOLENCE; HEALTH; PREVALENCE AB Background: This study explored demographic influences on veterans' reports of homelessness or imminent risk of homelessness with a particular focus on gender. Methods: We analyzed data for a cohort of veterans who responded to the U.S. Department of Veterans Affairs (VA), Veterans Health Administration (VHA) universal screener for homelessness and risk during a 3-month period. Multinomial mixed effects models stratified by gender predicted veterans' reports of homelessness or risk based on age, race, marital status, and receipt of VA compensation. Findings: The proportion of positive screens homelessness or risk was 2.7% for females and 1.7% for males. Women more likely to report being at risk of homelessness were aged 35 to 54 years, Black, and unmarried; those more likely to experience homelessness were Black and unmarried. Among male veterans, the greatest predictors of both homelessness and risk were Black race and unmarried status. Among both genders, receiving VA disability compensation was associated with lesser odds of being homeless or at risk. Conclusions: The findings describe the current population of veterans using VHA health care services who may benefit from homelessness prevention or intervention services, identify racial differences in housing stability, and distinguish subpopulations who may be in particular need of intervention. Interventions to address these needs are described. Published by Elsevier Inc. C1 [Montgomery, Ann Elizabeth] US Dept Vet Affairs, Natl Ctr Homelessness Vet, Philadelphia, PA 19146 USA. [Dichter, Melissa E.; Thomasson, Arwin M.; Fu, Xiaoying; Roberts, Christopher B.] US Dept Vet Affairs, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19146 USA. RP Montgomery, AE (reprint author), US Dept Vet Affairs, Natl Ctr Homelessness Vet, 4100 Chester Ave,Suite 201, Philadelphia, PA 19146 USA. EM ann.montgomery2@va.gov FU U.S. Department of Veterans Affairs; National Center on Homelessness Among Veterans; Center for Health Equity Research and Promotion [LIP 72-061] FX This study was funded by the U.S. Department of Veterans Affairs, National Center on Homelessness Among Veterans and Center for Health Equity Research and Promotion (Grant no. LIP 72-061). The contents of this article do not necessarily represent the views of the U.S. Department of Veterans Affairs or the U.S. Government. NR 38 TC 5 Z9 5 U1 5 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JAN-FEB PY 2015 VL 25 IS 1 BP 42 EP 48 DI 10.1016/j.whi.2014.10.003 PG 7 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA CN7GN UT WOS:000358602500008 PM 25498763 ER PT J AU Ketch, RA Rubin, RT Baker, MR Sones, AC Ames, D AF Ketch, Robert A. Rubin, Robert T. Baker, Matthew R. Sones, Alexander C. Ames, Donna TI Art appreciation for veterans with severe mental illness in a VA Psychosocial Rehabilitation and Recovery Center SO ARTS & HEALTH LA English DT Article DE veterans; mental health; art appreciation AB Considerable research has shown the positive effects of art, music and drama therapy on mental health and well-being. In September 2012, a weekly Art Appreciation class was initiated at the Veterans Affairs (VA) West Los Angeles (WLA) Psychosocial Rehabilitation and Recovery Center (PRRC) for veterans with severe mental illness. There are 106 VA PRRCs throughout the USA, designed to be transitional learning centers with curriculum-based interventions to help veterans re-integrate into the community and develop meaningful activities independent of the hospital setting. The VA WLA PRRC Art Appreciation class includes classroom sessions and community outings to local museums and other institutions holding art works of interest. It is taught at a college level and designed to lack the stigma of being a therapy group. Preliminary evidence from self-report measures indicates positive effects on mood, self-esteem, socialization and community participation among the veteran participants and recognition among staff that the course aids the veterans' recovery process. Appreciating art thus appears to promote both subjective and objective improvement in recovery and community re-integration for veterans who are experiencing chronic and disabling emotional distress. C1 [Ketch, Robert A.; Baker, Matthew R.; Sones, Alexander C.; Ames, Donna] VA Greater Los Angeles Healthcare Syst, West LA Psychosocial Rehabil & Recovery Ctr, Los Angeles, CA USA. [Rubin, Robert T.] VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA 90073 USA. [Rubin, Robert T.] Univ Calif Los Angeles, David Geffen Sch Med, Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. RP Rubin, RT (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA 90073 USA. EM rtrubin@yahoo.com NR 18 TC 0 Z9 0 U1 0 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1753-3015 EI 1753-3023 J9 ARTS HEALTH JI Arts Health PY 2015 VL 7 IS 2 BP 172 EP 181 DI 10.1080/17533015.2015.1019700 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA CM4TS UT WOS:000357678300008 ER PT S AU Brettman, AD Tan, PH Tran, K Shaw, SY AF Brettman, Ari D. Tan, Pauline H. Tran, Khoa Shaw, Stanley Y. BE Hempel, JE Williams, CH Hong, CC TI Applying the Logic of Genetic Interaction to Discover Small Molecules That Functionally Interact with Human Disease Alleles SO CHEMICAL BIOLOGY: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Chemical screen; Functional genomics; Chemical genetics; Chemical genomics; Drug repurposing; Genetic interaction ID AUTOPHAGY; RESOURCE AB Despite rapid advances in the genetics of complex human diseases, understanding the significance of human disease alleles remains a critical roadblock to clinical translation. Here, we present a chemical biology approach that uses perturbation with small molecules of known mechanism to reveal mechanistic and therapeutic consequences of human disease alleles. To maximize human applicability, we perform chemical screening on multiple cell lines isolated from individual patients, allowing the effects of disease alleles to be studied in their native genetic context. Chemical screen analysis combines the logic of traditional genetic interaction screens with analytic methods from high-dimensionality gene expression analyses. We rank compounds according to their ability to discriminate between cell lines that are mutant versus wild type at a disease gene (i.e., the compounds induce phenotypes that differ the most across the two classes). A technique called compound set enrichment analysis (CSEA), modeled after a widely used method to identify pathways from gene expression data, identifies sets of functionally or structurally related compounds that are statistically enriched among the most discriminating compounds. This chemical: genetic interaction approach was applied to patient-derived cells in a monogenic form of diabetes and identified several classes of compounds (including FDA-approved drugs) that show functional interactions with the causative disease gene, and also modulate insulin secretion, a critical disease phenotype. In summary, perturbation of patient-derived cells with small molecules of known mechanism, together with compound-set-based pathway analysis, can identify small molecules and pathways that functionally interact with disease alleles, and that can modulate disease networks for therapeutic effect. C1 [Brettman, Ari D.; Tan, Pauline H.; Tran, Khoa; Shaw, Stanley Y.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Brettman, Ari D.; Tan, Pauline H.; Tran, Khoa; Shaw, Stanley Y.] Harvard Univ, Sch Med, Boston, MA USA. [Brettman, Ari D.; Shaw, Stanley Y.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Brettman, AD (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. FU NCI NIH HHS [T32 CA079443, T32CA79443]; NHLBI NIH HHS [T32 HL007208, HHSN268201000044C, T32HL007208]; PHS HHS [HHSN268201000044C] NR 16 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-4939-2269-7; 978-1-4939-2268-0 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2015 VL 1263 BP 15 EP 27 DI 10.1007/978-1-4939-2269-7_2 D2 10.1007/978-1-4939-2269-7 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BD0OR UT WOS:000357509900003 PM 25618333 ER PT J AU Sarmiento, JM Venteicher, AS Patil, CG AF Sarmiento, J. Manuel Venteicher, Andrew S. Patil, Chirag G. TI Early versus delayed postoperative radiotherapy for treatment of low-grade gliomas SO COCHRANE DATABASE OF SYSTEMATIC REVIEWS LA English DT Review ID QUALITY-OF-LIFE; GAMMA-KNIFE SURGERY; TERM-FOLLOW-UP; PROGNOSTIC-FACTORS; RADIATION-THERAPY; RANDOMIZED-TRIAL; EUROPEAN-ORGANIZATION; CLINICAL-TRIALS; SUPRATENTORIAL GLIOMAS; HEMISPHERIC GLIOMAS AB Background In most people with low-grade gliomas (LGG), the primary treatment regimen remains a combination of surgery followed by postoperative radiotherapy. However, the optimal timing of radiotherapy is controversial. It is unclear whether to use radiotherapy in the early postoperative period, or whether radiotherapy should be delayed until tumour progression occurs. Objectives To assess the effects of early postoperative radiotherapy versus radiotherapy delayed until tumour progression for low-grade intracranial gliomas in people who had initial biopsy or surgical resection. Search methods We searched up to September 2014 the following electronic databases: the Cochrane Register of Controlled Trials (CENTRAL, Issue 8, 2014), MEDLINE (1948 to Aug week 3, 2014), and EMBASE (1980 to Aug week 3, 2014) to identify trials for inclusion in this Cochrane review. Selection criteria We included randomised controlled trials (RCTs) that compared early versus delayed radiotherapy following biopsy or surgical resection for the treatment of people with newly diagnosed intracranial LGG (astrocytoma, oligodendroglioma, mixed oligoastrocytoma, astroblastoma, xanthoastrocytoma, or ganglioglioma). Radiotherapy may include conformal external beam radiotherapy (EBRT) with linear accelerator or cobalt-60 sources, intensity-modulated radiotherapy (IMRT), or stereotactic radiosurgery (SRS). Data collection and analysis Three review authors independently assessed the trials for inclusion and risk of bias, and extracted study data. We resolved any differences between review authors by discussion. Adverse effects were also extracted from the study report. We performed meta-analyses using a random-effects model with inverse variance weighting. Main results We included one large, multi-institutional, prospective RCT, involving 311 participants; the risk of bias in this study was unclear. This study found that early postoperative radiotherapy is associated with an increase in time to progression compared to observation (and delayed radiotherapy upon disease progression) for people with LGG but does not significantly improve overall survival (OS). The median progression-free survival (PFS) was 5.3 years in the early radiotherapy group and 3.4 years in the delayed radiotherapy group (hazard ratio (HR) 0.59, 95% confidence interval (CI) 0.45 to 0.77; P value < 0.0001; 311 participants; 1 trail; low quality evidence). The median OS in the early radiotherapy group was 7.4 years, while the delayed radiotherapy group experienced a median overall survival of 7.2 years (HR 0.97, 95% CI 0.71 to 1.33; P value = 0.872; 311 participants; 1 trail; low quality evidence). The total dose of radiotherapy given was 54 Gy; five fractions of 1.8 Gy per week were given for six weeks. Adverse effects following radiotherapy consisted of skin reactions, otitis media, mild headache, nausea, and vomiting. Rescue therapy was provided to 65% of the participants randomised to delayed radiotherapy. People in both cohorts who were free from tumour progression showed no differences in cognitive deficit, focal deficit, performance status, and headache after one year. However, participants randomised to the early radiotherapy group experienced significantly fewer seizures than participants in the delayed postoperative radiotherapy group at one year (25% versus 41%, P value = 0.0329, respectively). Authors' conclusions Given the high risk of bias in the included study, the results of this analysis must be interpreted with caution. Early radiation therapy was associated with the following adverse effects: skin reactions, otitis media, mild headache, nausea, and vomiting. People with LGG who undergo early radiotherapy showed an increase in time to progression compared with people who were observed and had radiotherapy at the time of progression. There was no significant difference in overall survival between people who had early versus delayed radiotherapy; however, this finding may be due to the effectiveness of rescue therapy with radiation in the control arm. People who underwent early radiation had better seizure control at one year than people who underwent delayed radiation. There were no cases of radiation-induced malignant transformation of LGG. However, it remains unclear whether there are differences in memory, executive function, cognitive function, or quality of life between the two groups since these measures were not evaluated. C1 [Sarmiento, J. Manuel] Cedars Sinai Med Ctr, Dept Neurosurg, Los Angeles, CA 90048 USA. [Venteicher, Andrew S.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Patil, Chirag G.] Maxine Dunitz Neurosurg Inst, Dept Neurosurg, Los Angeles, CA USA. RP Venteicher, AS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, 55 Fruit St, Boston, MA 02114 USA. EM aventeicher@mgh.harvard.edu FU NIH R25 grant, USA; American Brain Tumor Association, USA; Neurosurgery Research and Education Foundation, USA FX External sources; NIH R25 grant, USA.; Fellowship to ASV; American Brain Tumor Association, USA.; Research support to ASV; Neurosurgery Research and Education Foundation, USA.; Research support to ASV NR 66 TC 1 Z9 1 U1 0 U2 2 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 2015 IS 6 AR CD009229 DI 10.1002/14651858.CD009229.pub2 PG 35 WC Medicine, General & Internal SC General & Internal Medicine GA CM3TE UT WOS:000357606400044 PM 26118544 ER PT J AU Berman, NC Stark, A Cooperman, A Wilhelm, S Cohen, IG AF Berman, Noah C. Stark, Abigail Cooperman, Allison Wilhelm, Sabine Cohen, I. Glenn TI Effect of Patient and Therapist Factors on Suicide Risk Assessment SO DEATH STUDIES LA English DT Article ID DECISION-MAKING; PERSONALITY-DISORDER; FOLLOW-UP; PREDICTORS; CLINICIAN; PREVALENCE; GUIDELINES; BEHAVIORS; DIAGNOSIS; ATTITUDES AB The present study examined how patient risk factors and clinician demographics predict the assessment of suicide risk. Clinicians (N=333) read two vignettes, one of which manipulated patient risk factors, then rated the patient's likelihood of suicide and need for hospitalization. Clinicians' assessments were heterogeneous. Results indicated that certain patient risk factors (access to excess medication) and clinician demographics (relationship status, religiosity) predicted perceived suicide risk; and, moreover, clinicians' suicide risk assessment did not always align with the decision to hospitalize the patient. The authors discuss methods for standardizing clinicians' judgment of risk and minimizing error through debiasing strategies (cognitive forcing strategy). C1 [Berman, Noah C.; Stark, Abigail; Cooperman, Allison; Wilhelm, Sabine] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Cohen, I. Glenn] Harvard Univ, Sch Law, Cambridge, MA 02138 USA. RP Berman, NC (reprint author), Massachusetts Gen Hosp, OCD, 185 Cambridge St,Suite 2000, Boston, MA 02114 USA. EM nberman@mgh.harvard.edu NR 35 TC 2 Z9 2 U1 0 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0748-1187 EI 1091-7683 J9 DEATH STUD JI Death Stud. PY 2015 VL 39 IS 7 BP 433 EP 441 DI 10.1080/07481187.2014.958630 PG 9 WC Psychology, Multidisciplinary; Social Issues; Social Sciences, Biomedical SC Psychology; Social Issues; Biomedical Social Sciences GA CM7JD UT WOS:000357866900005 PM 25674940 ER EF