FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Chou, YK Wu, SL Avendano, C Caldwell, T Maniaci, B Yomogida, K Zhu, Y Chu, CQ AF Chou, Yuan K. Wu, Shili Avendano, Camilo Caldwell, Tom Maniaci, Brian Yomogida, Kentaro Zhu, Yong Chu, Cong-Qiu TI Supercharged Sox9 Protein Induces Chondrogenic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Chou, Yuan K.; Yomogida, Kentaro; Chu, Cong-Qiu] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Wu, Shili; Avendano, Camilo; Caldwell, Tom; Maniaci, Brian; Zhu, Yong] VivoScript Inc, Costa Mesa, CA USA. [Chu, Cong-Qiu] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 8 BP S3 EP S3 PG 1 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748300009 ER PT J AU Chu, CQ Austin, CR Doyle, TM Goodwin, KA El Torgomen, N Treudler, R Martin, TM AF Chu, Cong-Qiu Austin, Carrie R. Doyle, Trudy M. Goodwin, Kelley A. El Torgomen, Noha Treudler, Regina Martin, Tammy M. TI NLRP3 Gene Analysis for Patients with Schnitzler's Syndrome SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Chu, Cong-Qiu; Austin, Carrie R.; Doyle, Trudy M.; Goodwin, Kelley A.; El Torgomen, Noha; Martin, Tammy M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Chu, Cong-Qiu] Portland VA Med Ctr, Portland, OR USA. [Treudler, Regina] Univ Klinikum Leipzig AoR, Leipzig, Germany. NR 2 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 190 BP S81 EP S81 PG 1 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748300191 ER PT J AU Davis, LA Polk, BI Mann, AD Kerr, GS Reimold, AM Cannon, GW Mikuls, TR Caplan, L AF Davis, Lisa A. Polk, Brooke Ivan Mann, Alyse D. Kerr, Gail S. Reimold, Andreas M. Cannon, Grant W. Mikuls, Ted R. Caplan, Liron TI Methotrexate Adverse Events in a Cohort of US Veterans with Rheumatoid Arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Davis, Lisa A.; Polk, Brooke Ivan; Caplan, Liron] Univ Colorado, Sch Med, Aurora, CO USA. [Mann, Alyse D.] Denver VA Med Ctr, Denver, CO USA. [Kerr, Gail S.] Georgetown & Howard Univ, Washington DC VAMC, Washington, DC USA. [Reimold, Andreas M.] Dallas VA, Dallas, TX USA. [Reimold, Andreas M.] Univ Texas SW, Dallas, TX USA. [Cannon, Grant W.] George E Wahlen VA Med Ctr, Salt Lake City, UT USA. [Mikuls, Ted R.] Univ Nebraska Med Ctr, Omaha, NE USA. [Mikuls, Ted R.] Omaha VA, Omaha, NE USA. [Caplan, Liron] Denver VA, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 2640 BP S1119 EP S1119 PG 1 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748306150 ER PT J AU Davis, LA Polk, BI Mann, AD Wolff, RK Kerr, GS Reimold, AM Cannon, GW Mikuls, TR Caplan, L AF Davis, Lisa A. Polk, Brooke Ivan Mann, Alyse D. Wolff, Roger K. Kerr, Gail S. Reimold, Andreas M. Cannon, Grant W. Mikuls, Ted R. Caplan, Liron TI Folic Acid Pathway Single Neucelotide Polymorphisms Associated with Methotrexate-Related Significant Adverse Events. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Davis, Lisa A.; Polk, Brooke Ivan; Caplan, Liron] Univ Colorado, Sch Med, Aurora, CO USA. [Mann, Alyse D.] Denver VA Med Ctr, Denver, CO USA. [Wolff, Roger K.] Univ Utah, Salt Lake City, UT USA. [Kerr, Gail S.] Georgetown & Howard Univ, Washington DC VAMC, Washington, DC USA. [Reimold, Andreas M.] Univ Texas SW, Dallas, TX USA. [Reimold, Andreas M.] Dallas VA, Dallas, TX USA. [Cannon, Grant W.] George E Wahlen VA Med Ctr, Salt Lake City, UT USA. [Mikuls, Ted R.] Univ Nebraska Med Ctr, Omaha, NE USA. [Mikuls, Ted R.] Omaha VA, Omaha, NE USA. [Caplan, Liron] Denver VA, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 2483 BP S1047 EP S1048 PG 2 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748305403 ER PT J AU DeBerardine, M Fisher, MC Keenan, RT Pillinger, MH Crittenden, DB AF DeBerardine, Michael Fisher, Mark C. Keenan, Robert T. Pillinger, Michael H. Crittenden, Daria B. TI Low-Dose Allopurinol Promotes Greater Serum Urate Lowering in Gout Patients with Chronic Kidney Disease Vs Normal Renal Function. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [DeBerardine, Michael; Pillinger, Michael H.; Crittenden, Daria B.] NYU, Sch Med, Div Rheumatol, New York, NY USA. [Fisher, Mark C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Keenan, Robert T.] Duke Univ, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 166 BP S72 EP S72 PG 1 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748300167 ER PT J AU Deng, Y Zhao, J Sakurai, D Kaufman, KM Edberg, JC Kimberly, RP Kamen, DL Gilkeson, GS Jacob, CO Scofield, RH Langefeld, CD Kelly, JA Alarcuun-Riquelme, ME Harley, JB Vyse, TJ Freedman, BI Gaffney, PM Sivils, KM James, JA Niewold, TB Cantor, RM Chen, WL Hahn, BH Brown, EE Tsao, BP AF Deng, Yun Zhao, Jian Sakurai, Daisuke Kaufman, Kenneth M. Edberg, Jeffrey C. Kimberly, Robert P. Kamen, Diane L. Gilkeson, Gary S. Jacob, Chaim O. Scofield, Robert H. Langefeld, Carl D. Kelly, Jennifer A. Alarcuen-Riquelme, Marta E. Harley, John B. Vyse, Timothy J. Freedman, Barry I. Gaffney, Patrick M. Sivils, Kathy Moser James, Judith A. Niewold, Timothy B. Cantor, Rita M. Chen, Weiling Hahn, Bevra H. Brown, Elizabeth E. Tsao, Betty P. CA BIOLUPUS & GENLES Networks PROFILE TI The SLE-Associated TLR7 Variant Confers Differential Gene Expression Modulated by Microrna-3148 SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Deng, Yun; Zhao, Jian; Sakurai, Daisuke; Chen, Weiling; Hahn, Bevra H.; Tsao, Betty P.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Kaufman, Kenneth M.; Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH USA. [Kaufman, Kenneth M.; Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Ctr Autoimmune Genom & Etiol, Cincinnati, OH USA. [Kaufman, Kenneth M.; Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [Edberg, Jeffrey C.; Kimberly, Robert P.; Brown, Elizabeth E.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Kamen, Diane L.; Scofield, Robert H.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Program, Charleston, SC USA. [Gilkeson, Gary S.] Med Univ S Carolina, Charleston, SC 29425 USA. [Jacob, Chaim O.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA. [Scofield, Robert H.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Scofield, Robert H.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. [Langefeld, Carl D.] Wake Forest Univ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA. [Gaffney, Patrick M.; James, Judith A.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Program, Oklahoma City, OK 73104 USA. [Alarcuen-Riquelme, Marta E.] Pfizer Univ Granada Junta de Andalucia, Ctr Genom & Invest Oncol GENYO, Granada, Spain. [Vyse, Timothy J.] Kings Coll London, Div Genet, London WC2R 2LS, England. [Vyse, Timothy J.] Kings Coll London, Div Mol Med & Immunol, London WC2R 2LS, England. [Freedman, Barry I.] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA. [Niewold, Timothy B.] Univ Chicago, Sect Rheumatol, Chicago, IL 60637 USA. [Niewold, Timothy B.] Univ Chicago, Gwen Knapp Ctr Lupus & Immunol Res, Chicago, IL 60637 USA. [Cantor, Rita M.] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA. RI Zhao, Jian/E-6292-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 1613 BP S689 EP S689 PG 1 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748303334 ER PT J AU Domsic, RT Nihtyanova, S Wisniewski, SR Fine, MJ Kwoh, CK Denton, CP Medsger, TA AF Domsic, Robyn T. Nihtyanova, Svetlana Wisniewski, Stephen R. Fine, Michael J. Kwoh, C. Kent Denton, Christopher P. Medsger, Thomas A., Jr. TI External Validation of a Two-Year Mortality Risk Prediction Rule in Early Diffuse Systemic Sclerosis Patients. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Wisniewski, Stephen R.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Nihtyanova, Svetlana] Royal Free Hosp, Sch Med, London, England. [Fine, Michael J.] VA Pittsburgh Healthcare, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Kwoh, C. Kent] VA Healthcare Syst, Pittsburgh, PA USA. [Denton, Christopher P.] UCL, London, England. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 698 BP S299 EP S300 PG 2 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748301236 ER PT J AU Edberg, JC Duarte, CW Patki, A Brown, EE Kaufman, KM Kelly, JA Comeau, ME Alarcon-Riquelme, ME Bae, SC Criswell, LA Freedman, BI Gaffney, PM Gilkeson, GS Jacob, CO James, JA Kamen, DL Sivils, KM Niewold, TB Scofield, RH Tsao, BP Vyse, TJ Harley, JB Langefeld, CD Tiwari, H Kimberly, RP AF Edberg, Jeffrey C. Duarte, Christine W. Patki, Amit Brown, Elizabeth E. Kaufman, Kenneth M. Kelly, Jennifer A. Comeau, Mary E. Alarcon-Riquelme, Marta E. Bae, Sang-Cheol Criswell, Lindsey A. Freedman, Barry I. Gaffney, Patrick M. Gilkeson, Gary S. Jacob, Chaim O. James, Judith A. Kamen, Diane L. Sivils, Kathy Moser Niewold, Timothy B. Scofield, Robert H. Tsao, Betty P. Vyse, Timothy J. Harley, John B. Langefeld, Carl D. Tiwari, Hemant Kimberly, Robert P. CA BIOLUPUS GENLES TI Genetic Interactions Between SNP Variants in C3 Receptor Sub-units in Patients with SLE. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Edberg, Jeffrey C.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Kaufman, Kenneth M.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Comeau, Mary E.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [GENLES] Univ Granada, Ctr Genom & Oncol Res Pfizer, Oklahoma Med Res Fdn, Oklahoma City, OK USA. [Bae, Sang-Cheol] Hanyang Univ Hosp Rheumat Dis, CRCRA, Seoul, South Korea. [Criswell, Lindsey A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Freedman, Barry I.] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA. [Gaffney, Patrick M.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Program, Oklahoma City, OK 73104 USA. [Gilkeson, Gary S.] Med Univ S Carolina, Charleston, SC 29425 USA. [Jacob, Chaim O.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA. [Scofield, Robert H.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Scofield, Robert H.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Program, Charleston, SC USA. [Scofield, Robert H.; Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati Childrens Hosp Med Ctr, Oklahoma City, OK USA. [Tsao, Betty P.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Vyse, Timothy J.] Kings Coll London, Div Genet, London WC2R 2LS, England. [Vyse, Timothy J.] Kings Coll London, Div Mol Med & Immunol, London WC2R 2LS, England. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 970 BP S420 EP S420 PG 1 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748302045 ER PT J AU Foering, K Chang, AY Piette, EW Okawa, J Werth, VP AF Foering, Kristen Chang, Aileen Y. Piette, Evan W. Okawa, Joyce Werth, Victoria P. TI Characterization of Clinical Photosensitivity in Cutaneous Lupus Erythematosus. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Okawa, Joyce] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Foering, Kristen] VAMC, Philadelphia, PA USA. [Okawa, Joyce; Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 1401 BP S603 EP S603 PG 1 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748303122 ER PT J AU Friday, RP Means, TK Tai, M Sadik, CD Luster, AD AF Friday, Robert P. Means, Terry K. Tai, Melissa Sadik, Christian D. Luster, Andrew D. TI CCR1 Potentiates Gouty Inflammation Following Initial CXCR2-Dependent Neutrophil Recruitment to Sites of Monosodium Urate Crystal Deposition in Mice. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Friday, Robert P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Means, Terry K.; Tai, Melissa; Sadik, Christian D.; Luster, Andrew D.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 1661 BP S710 EP S710 PG 1 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748303382 ER PT J AU Garg, V Maranian, P Taylor, MB Paulus, HE Elashoff, D Ranganath, VK AF Garg, Vikram Maranian, Paul Taylor, Mihaela B. Paulus, Harold E. Elashoff, David Ranganath, Veena K. TI DAS28 Is Not a Sufficient Disease Activity Measure for Obese Rheumatoid Arthritis Patients - Don't Leave the Feet Behind SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Garg, Vikram] UCLA David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Maranian, Paul] UCLA Med Sch, Los Angeles, CA USA. [Ranganath, Veena K.] Univ Calif Los Angeles, Western Consortium Practicing Rheumatologists, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 391 BP S170 EP S171 PG 2 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748300392 ER PT J AU Giles, BM Zhao, J Lough, KM Gaffney, PM Alarcon-Riquelme, ME Brown, EE Criswell, LA Gilkeson, GS Jacob, CO James, JA Merrill, JT Moser, KL Niewold, TB Scofield, RH Vyse, TJ Harley, JB Kaufman, KM Kelly, JA Langefeld, CD Edberg, JC Kimberly, RP Ulgiati, D Tsao, BP Boackle, SA AF Giles, Brendan M. Zhao, Jian Lough, Kara M. Gaffney, Patrick M. Alarcon-Riquelme, Marta E. Brown, Elizabeth E. Criswell, Lindsey A. Gilkeson, Gary S. Jacob, Chaim O. James, Judith A. Merrill, Joan T. Moser, Kathy L. Niewold, Timothy B. Scofield, R. Hal Vyse, Timothy J. Harley, John B. Kaufman, Kenneth M. Kelly, Jennifer A. Langefeld, Carl D. Edberg, Jeffrey C. Kimberly, Robert P. Ulgiati, Daniela Tsao, Betty P. Boackle, Susan A. CA LLAS2 BIOLUPUS PROFILE TI Preferential Association of Complement Receptor 2 Variants with Anti-dsDNA Autoantibodies in Systemic Lupus Erythematosus. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Giles, Brendan M.; Lough, Kara M.; Boackle, Susan A.] Univ Colorado, Sch Med, Aurora, CO USA. [Zhao, Jian] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Alarcon-Riquelme, Marta E.; BIOLUPUS] Univ Granada Junta de Andalucia, Ctr Genom & Oncol Res Pfizer, Oklahoma Med Res Fdn, Oklahoma City, OK USA. [Edberg, Jeffrey C.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Criswell, Lindsey A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Gilkeson, Gary S.] Med Univ S Carolina, Charleston, SC 29425 USA. [Jacob, Chaim O.] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA. [James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Niewold, Timothy B.] Univ Chicago, Chicago, IL 60637 USA. [Vyse, Timothy J.] Kings Coll London, Guys Hosp, London WC2R 2LS, England. [Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [Langefeld, Carl D.] Wake Forest Sch Med, Winston Salem, NC USA. [Ulgiati, Daniela] Univ Western Australia, Perth, WA 6009, Australia. [Tsao, Betty P.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RI Zhao, Jian/E-6292-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 2283 BP S965 EP S966 PG 2 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748305203 ER PT J AU Jain, A Belsom, R Curtis, J Yang, S Mikuls, TR Chen, L Gaffo, AL AF Jain, Archana Belsom, Rebecca Curtis, Jeffrey Yang, Shuo Mikuls, Ted R. Chen, Lang Gaffo, Angelo L. TI Patient Characteristics Associated with Discrepancies in Evaluator-Reported and Patient-Reported Outcomes in US Veterans with Rheumatoid Arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Jain, Archana; Belsom, Rebecca; Curtis, Jeffrey; Yang, Shuo; Chen, Lang; Gaffo, Angelo L.] Univ Alabama Birmingham, Birmingham, AL USA. [Mikuls, Ted R.] Univ Nebraska Med Ctr, Omaha, NE USA. [Mikuls, Ted R.] Omaha VA, Omaha, NE USA. [Gaffo, Angelo L.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 2106 BP S891 EP S891 PG 1 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748305026 ER PT J AU Khosroshahi, A Cheryk, LA Carruthers, M Edwards, JA Bloch, DB Stone, JH AF Khosroshahi, Arezou Cheryk, Lynn A. Carruthers, Mollie Edwards, Judith A. Bloch, Donald B. Stone, John H. TI Prozone Phenomenon Leads to Low IgG4 Concentrations in IgG4-Related Disease. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Khosroshahi, Arezou; Carruthers, Mollie; Bloch, Donald B.; Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cheryk, Lynn A.; Edwards, Judith A.] Mayo Med Labs, Andover, MA USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 2527 BP S1067 EP S1067 PG 1 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748306037 ER PT J AU Khosroshahi, A Lee, L Carruthers, M Acu, R Bonaffini, P Deshpande, V Sahani, D Stone, JH AF Khosroshahi, Arezou Lee, Leslie Carruthers, Mollie Acu, Rusen Bonaffini, Pietro Deshpande, Vikram Sahani, Dushyant Stone, John H. TI Utility of PET-CT Imaging in IgG4-Related Disease SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Khosroshahi, Arezou; Lee, Leslie; Carruthers, Mollie; Acu, Rusen; Bonaffini, Pietro; Deshpande, Vikram; Sahani, Dushyant; Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 133 BP S58 EP S58 PG 1 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748300134 ER PT J AU Kimberly, RP Freedman, BI Langfeld, CD Absher, D Andringa, KK Birmingham, D Brown, EE Comeau, ME Costenbader, KH Criswell, LA Edberg, JC Harley, JB James, JA Kamen, DL Merrill, JT Niewold, TB Patel, N Petri, MA Ramsey-Goldman, R Salmon, JE Segal, M Sivils, KM Tsao, BP Julian, BA AF Kimberly, Robert P. Freedman, Barry I. Langfeld, Carl D. Absher, Devin Andringa, Kelly K. Birmingham, Daniel Brown, Elizabeth E. Comeau, Mary E. Costenbader, Karen H. Criswell, Lindsey A. Edberg, Jeffrey C. Harley, John B. James, Judith A. Kamen, Diane L. Merrill, Joan T. Niewold, Timothy B. Patel, Neha Petri, Michelle A. Ramsey-Goldman, Rosalind Salmon, Jane E. Segal, Mark Sivils, Kathy Moser Tsao, Betty P. Julian, Bruce A. CA Lupus Nephritis-ESRD Consortium TI Apolipoprotein L1 Risk Variants Underlie Racial Disparities in Lupus Nephritis-Induced End-Stage Renal Disease SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Kimberly, Robert P.; Andringa, Kelly K.; Brown, Elizabeth E.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Freedman, Barry I.] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA. [Langfeld, Carl D.; Comeau, Mary E.] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Absher, Devin] HudsonAlpha Inst Biotechnol, Huntsville, AL USA. [Birmingham, Daniel] Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. [Costenbader, Karen H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Criswell, Lindsey A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Edberg, Jeffrey C.; Julian, Bruce A.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [James, Judith A.; Merrill, Joan T.; Sivils, Kathy Moser] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Kamen, Diane L.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Program, Charleston, SC USA. [Niewold, Timothy B.] Univ Chicago, Chicago, IL 60637 USA. [Patel, Neha] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. [Petri, Michelle A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Ramsey-Goldman, Rosalind] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Salmon, Jane E.] Hosp Special Surg, New York, NY 10021 USA. [Segal, Mark] Univ Florida, Gainesville, FL USA. [Tsao, Betty P.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 729 BP S313 EP S313 PG 1 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748301266 ER PT J AU Lessard, CJ Li, H Adrianto, I Ice, JA Jonsson, R Illei, GG Rischmueller, M Nordmark, G Mariette, X Miceli-Richard, C Wahren-Herlenius, M Witte, T Brennan, MT Omdal, R Gaffney, PM Lessard, JA Ng, WF Rhodus, NL Segal, BM Scofield, RH James, JA Anaya, JM Harley, JB Montgomery, CG Sivils, KM AF Lessard, Christopher J. Li, He Adrianto, Indra Ice, John A. Jonsson, Roland Illei, Gabor G. Rischmueller, Maureen Nordmark, Gunnel Mariette, Xavier Miceli-Richard, Corinne Wahren-Herlenius, Marie Witte, Torsten Brennan, Michael T. Omdal, Roald Gaffney, Patrick M. Lessard, James A. Ng, Wan-Fai Rhodus, Nelson L. Segal, Barbara M. Scofield, R. Hal James, Judith A. Anaya, Juan-Manuel Harley, John B. Montgomery, Courtney G. Sivils, Kathy Moser TI A Genome-Wide Association Study Establishes Muliple Susceptibility Loci for Sjogren's Syndrome SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Lessard, Christopher J.; James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma Med Res Fdn, Oklahoma City, OK USA. [Jonsson, Roland] Univ Bergen, Bergen, Norway. [Illei, Gabor G.] NIDCR, NIH, Bethesda, MD USA. [Rischmueller, Maureen] Queen Elizabeth Hosp, Adelaide, SA, Australia. [Mariette, Xavier] Univ Paris 11, Le Kremlin Bicetre, France. [Miceli-Richard, Corinne] Hop Bicetre, Le Kremlin Bicetre, France. [Wahren-Herlenius, Marie] Karolinska Inst, Stockholm, Sweden. [Witte, Torsten] Hannover Med Sch, Hannover, Germany. [Brennan, Michael T.] Carolinas Med Ctr, Charlotte, NC 28203 USA. [Omdal, Roald] Stavanger Univ Hosp, Clin Immunol Unit, Dept Internal Med, Stavanger, Norway. [Gaffney, Patrick M.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Program, Oklahoma City, OK 73104 USA. [Lessard, James A.] Valley Bone & Joint Clin, Grand Forks, ND USA. [Ng, Wan-Fai] Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Rhodus, Nelson L.] Univ Minnesota, Minneapolis, MN USA. [Segal, Barbara M.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. [Anaya, Juan-Manuel] Univ Rosario Corp Invest Biol, Bogota, Colombia. [Harley, John B.] US Dept Vet Affairs, Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. RI Adrianto, Indra/D-4214-2013; Witte, Torsten/B-5783-2016; Anaya, Juan-Manuel/J-1960-2016 OI Adrianto, Indra/0000-0002-9973-3057; Anaya, Juan-Manuel/0000-0002-6444-1249 NR 0 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 2671 BP S1133 EP S1133 PG 1 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748306181 ER PT J AU Li, H Hsu, HC Wu, Q Yang, PA Li, J Cua, D Oukka, M Mountz, JD AF Li, Hao Hsu, Hui-Chen Wu, Qi Yang, PingAr Li, Jun Cua, Daniel Oukka, Mohamed Mountz, John D. TI IL-23 Controls Autoimmunity by Facilitating Clearance of Apoptotic Bodies in the Marginal Zone in Lupus-Prone BXD2 Mice SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Li, Hao; Hsu, Hui-Chen; Wu, Qi; Yang, PingAr; Li, Jun; Oukka, Mohamed; Mountz, John D.] Univ Alabama Birmingham, Birmingham, AL USA. [Cua, Daniel] Merck Res Lab, Palo Alto, CA USA. [Mountz, John D.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 2677 BP S1135 EP S1136 PG 2 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748306187 ER PT J AU Li, H Ice, JA Kelly, JA Adrianto, I Glenn, SB Hefner, KS Vista, EG Stone, DU Gopalakrishnan, R Houston, GD Lewis, DM Rohrer, M Hughes, P Harley, JB Montgomery, CG Chodosh, J Lessard, JA Anaya, JM Segal, BM Rhodus, NL Radfar, L Frank, MB Scofield, RH Lessard, CJ Sivils, KM AF Li, He Ice, John A. Kelly, Jennifer A. Adrianto, Indra Glenn, Stuart B. Hefner, Kimberly S. Vista, Evan G. Stone, Donald U. Gopalakrishnan, Raj Houston, Glen D. Lewis, David M. Rohrer, Michael Hughes, Pamela Harley, John B. Montgomery, Courtney G. Chodosh, James Lessard, James A. Anaya, Juan-Manuel Segal, Barbara M. Rhodus, Nelson L. Radfar, Lida Frank, Mark B. Scofield, R. Hal Lessard, Christopher J. Sivils, Kathy Moser TI Cis-Expression Quantitative Trait Loci Analysis of Dysregulated Interferon-Pathway Genes Identifies HLA-C and OAS1 As Novel Candidates for Susceptibility to Sjogren's Syndrome SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Li, He; Lessard, Christopher J.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma Med Res Fdn, Oklahoma City, OK USA. [Hefner, Kimberly S.] Hefner Eye Care & Opt Ctr, Oklahoma City, OK USA. [Vista, Evan G.] Uni Santo Tomas, Taguig City, Philippines. [Gopalakrishnan, Raj; Rohrer, Michael; Hughes, Pamela; Rhodus, Nelson L.] Univ Minnesota, Minneapolis, MN USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati Childrens Hosp, Cincinnati, OH USA. [Lessard, James A.] Valley Bone & Joint Clin, Grand Forks, ND USA. [Anaya, Juan-Manuel] Univ Rosario Corp Invest Biol, Bogota, Colombia. [Segal, Barbara M.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. RI Adrianto, Indra/D-4214-2013; Anaya, Juan-Manuel/J-1960-2016 OI Adrianto, Indra/0000-0002-9973-3057; Anaya, Juan-Manuel/0000-0002-6444-1249 NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 2674 BP S1134 EP S1134 PG 1 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748306184 ER PT J AU Li, J Hsu, HC Yang, PA Wu, Q Spalding, DM Chatham, WW Kimberly, RP Bridges, SL Mountz, JD AF Li, Jun Hsu, Hui-Chen Yang, PingAr Wu, Qi Spalding, David M. Chatham, W. Winn Kimberly, Robert P. Bridges, S. Louis, Jr. Mountz, John D. TI Inhibition of Fucose Incorporation Abrogates the Development of Arthritis by Suppressing the Inflammatory Macrophage Development and TNF-alpha Production. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Li, Jun; Hsu, Hui-Chen; Yang, PingAr; Wu, Qi; Spalding, David M.; Chatham, W. Winn; Kimberly, Robert P.; Bridges, S. Louis, Jr.; Mountz, John D.] Univ Alabama Birmingham, Birmingham, AL USA. [Hsu, Hui-Chen; Mountz, John D.] Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 2152 BP S910 EP S911 PG 2 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748305072 ER PT J AU Lo, GH McAlindon, TE Hawker, GA Driban, JB Price, LL Song, J Eaton, C Hochberg, MC Jackson, RD Kwoh, CK Nevitt, MC Dunlop, DD AF Lo, Grace H. McAlindon, Timothy E. Hawker, Gillian A. Driban, Jeffrey B. Price, Lori Lyn Song, Jing Eaton, Charles Hochberg, Marc C. Jackson, Rebecca D. Kwoh, C. Kent Nevitt, Michael C. Dunlop, Dorothy D. TI Knee Osteoarthritis Symptom Assessments That Combine Pain and Physical Activity Are Superior to Pain Alone. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Lo, Grace H.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [McAlindon, Timothy E.; Driban, Jeffrey B.; Price, Lori Lyn] Tufts Med Ctr, Boston, MA USA. [Hawker, Gillian A.] Univ Toronto, Womens Coll Res Inst, Toronto, ON, Canada. [Song, Jing; Dunlop, Dorothy D.] Northwestern Univ, Chicago, IL 60611 USA. [Eaton, Charles] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Eaton, Charles] Univ Maryland, Baltimore, MD 21201 USA. [Jackson, Rebecca D.] Ohio State Univ, Columbus, OH 43210 USA. [Kwoh, C. Kent] Univ Pittsburgh, Pittsburgh, PA USA. [Kwoh, C. Kent] VA Healthcare Syst, Pittsburgh, PA USA. [Nevitt, Michael C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 239 BP S103 EP S103 PG 1 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748300240 ER PT J AU Lu, PY Kottyan, LC Pinney, SM James, JA Xie, CC Buckholz, JM Harley, JB AF Lu, Pai-Yue Kottyan, Leah C. Pinney, Susan M. James, Judith A. Xie, Changchun Buckholz, Jeanette M. Harley, John B. TI Identifying a Link Between Uranium Exposure and Systemic Lupus Erythematosus in a Community Living near a Uranium Plant. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Lu, Pai-Yue; Kottyan, Leah C.; Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Pinney, Susan M.; Xie, Changchun; Buckholz, Jeanette M.] Univ Cincinnati, Cincinnati, OH USA. [James, Judith A.] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [James, Judith A.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 1606 BP S686 EP S686 PG 1 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748303327 ER PT J AU Mattoo, H Khosroshahi, A Mahajan, V Carruthers, M Stone, J Pillai, S AF Mattoo, Hamid Khosroshahi, Arezou Mahajan, Vinay Carruthers, Mollie Stone, John Pillai, Shiv TI Depletion of CD4-Effector Memory T Cells and Clonally Expanded IgG4 Memory B Cells May Explain the Therapeutic Efficacy of Rituximab in IgG4-Related Disease: Studies Using Flow Cytometry and Single-Cell Sequencing SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Mattoo, Hamid; Mahajan, Vinay; Stone, John] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 1752 BP S750 EP S750 PG 1 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748304029 ER PT J AU Miloslavsky, E Specks, U Stone, JH AF Miloslavsky, Eli Specks, Ulrich Stone, John H. CA RAVE ITN Res Grp TI Primary Endpoint Failure in the Rituximab in ANCA-Associated Vasculitis Trial. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Miloslavsky, Eli; Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Specks, Ulrich] Mayo Clin, Rochester, MN USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 1654 BP S707 EP S707 PG 1 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748303375 ER PT J AU Mittoo, S Frankel, S LeSage, D Castelino, FV Christopher-Stine, L Danoff, S Fischer, A Hummers, LK Shah, AA Swigris, JJ Cena, S Ferguson, S Garcia-Valladares, I Tran, M Grewal, HK Saketkoo, LA AF Mittoo, Shikha Frankel, Sid LeSage, Daphne Castelino, Flavia V. Christopher-Stine, Lisa Danoff, Sonye Fischer, Aryeh Hummers, Laura K. Shah, Ami A. Swigris, Jeffery J. Cena, Spohia Ferguson, Sancia Garcia-Valladares, Ignacio Maithy Tran Grewal, Harmanjot K. Saketkoo, Lesley Ann TI Patient Perspective Informs Core Sets, Constructs of Metrics and Communication Tools for Patients with Connective Tissue Disease Related Interstitial Lung Disease SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Mittoo, Shikha; Maithy Tran] Univ Toronto, Toronto, ON, Canada. [Frankel, Sid] Univ Manitoba, Winnipeg, MB, Canada. [LeSage, Daphne] Ctr CCH State Louisiana, New Orleans, LA USA. [Castelino, Flavia V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Christopher-Stine, Lisa; Hummers, Laura K.; Shah, Ami A.] Johns Hopkins Univ, Baltimore, MD USA. [Danoff, Sonye] Johns Hopkins Sch Med, Baltimore, MD USA. [Fischer, Aryeh; Swigris, Jeffery J.] Natl Jewish Hlth, Denver, CO USA. [Cena, Spohia; Garcia-Valladares, Ignacio; Grewal, Harmanjot K.; Saketkoo, Lesley Ann] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. [Ferguson, Sancia] Tulane Univ, Sch Med, New Orleans, LA 70118 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 1468 BP S630 EP S631 PG 2 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748303189 ER PT J AU Mountz, JD Wang, JH New, JS Yang, P Wu, Q Luo, B Li, J Druey, KM Hsu, HC AF Mountz, John D. Wang, John H. New, James S. Yang, PingAr Wu, Qi Luo, Bao Li, Jun Druey, Kirk M. Hsu, Hui-Chen TI Inhibition of Pathogenic Autoantibodies by Accelerating the Exit of Germinal Center B Cells Via Manipulation of Regulator of G-Protein Signaling SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Mountz, John D.; New, James S.; Yang, PingAr; Wu, Qi; Luo, Bao; Li, Jun; Hsu, Hui-Chen] Univ Alabama Birmingham, Birmingham, AL USA. [Mountz, John D.] Birmingham VA Med Ctr, Birmingham, AL USA. [Wang, John H.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Druey, Kirk M.] NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 2575 BP S1090 EP S1090 PG 1 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748306085 ER PT J AU O'Dell, JR Mikuls, TR Taylor, T Ahluwalia, V Brophy, M Warren, S Lew, R Phibbs, C Anis, AH Cannella, AC Kunkel, GA Erickson, AR Keystone, E AF O'Dell, James R. Mikuls, Ted R. Taylor, Thomas Ahluwalia, Vandana Brophy, Mary Warren, Stuart Lew, Robert Phibbs, Ciaran Anis, Aslam H. Cannella, Amy C. Kunkel, Gary A. Erickson, Alan R. Keystone, Edward CA CSP551 RACAT Res Grp TI Rheumatoid Arthritis Comparison of Active Therapies in Methotrexate Suboptimal Responders: Validation of the Strategy of Conventional Disease Modifying Anti-Rheumatic Drugs Before Biologicals SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [O'Dell, James R.; Mikuls, Ted R.; Cannella, Amy C.; Erickson, Alan R.] Univ Nebraska Med Ctr, Omaha, NE USA. [O'Dell, James R.; Mikuls, Ted R.; Cannella, Amy C.; Erickson, Alan R.] Omaha VA, Omaha, NE USA. [Taylor, Thomas] VA Med Ctr, White River Jct, VT USA. [Ahluwalia, Vandana] William Osler Hlth Ctr, Mississauga, ON, Canada. [Brophy, Mary; Lew, Robert] VA Boston Healthcare Syst, Boston, MA USA. [Warren, Stuart] VA CSP Clin Res Pharm Coordinating Ctr, Albuquerque, NM USA. [Phibbs, Ciaran] Palo Alto VA Hlth Care Syst, Menlo Pk, CA USA. [Anis, Aslam H.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Kunkel, Gary A.] George Wahlen Vet Affairs Med Ctr, Salt Lake City, UT USA. [Keystone, Edward] Univ Toronto, Toronto, ON, Canada. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 1287 BP S551 EP S552 PG 2 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748303008 ER PT J AU Quinzanos, I Hirsh, JM Caplan, L AF Quinzanos, Itziar Hirsh, Joel M. Caplan, Liron TI Correlations of Single Item Health Literacy Screening Questions with Established Measures of Health Literacy in Subjects with Rheumatoid Arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Quinzanos, Itziar; Hirsh, Joel M.] Denver Hlth Med Ctr, Denver, CO USA. [Caplan, Liron] Denver VAMC, Aurora, CO USA. [Caplan, Liron] Univ Colorado, Sch Med, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 91 BP S41 EP S41 PG 1 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748300092 ER PT J AU Rasmussen, A Ice, JA Li, H Grundahl, K Kelly, JA Radfar, L Hefner, KS Stone, DU Anaya, JM Rohrer, M Houston, GD Lewis, DM Chodosh, J Harley, JB Hughes, P Maier-Moore, JS Montgomery, CG Rhodus, NL Farris, AD Segal, BM Lessard, CJ Scofield, RH Sivils, KM AF Rasmussen, Astrid Ice, John A. Li, He Grundahl, Kiely Kelly, Jennifer A. Radfar, Lida Hefner, Kimberly S. Stone, Donald U. Anaya, Juan-Manuel Rohrer, Michael Houston, Glen D. Lewis, David M. Chodosh, James Harley, John B. Hughes, Pamela Maier-Moore, Jacen S. Montgomery, Courtney G. Rhodus, Nelson L. Farris, A. Darise Segal, Barbara M. Lessard, Christopher J. Scofield, R. Hal Sivils, Kathy Moser TI Effects of Reclassification Using the American College of Rheumatology Criteria On a Large cohort Sjogren's Syndrome Patients. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Rasmussen, Astrid; Ice, John A.; Li, He; Grundahl, Kiely; Kelly, Jennifer A.; Montgomery, Courtney G.; Lessard, Christopher J.; Sivils, Kathy Moser] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. [Radfar, Lida; Stone, Donald U.; Houston, Glen D.; Lewis, David M.; Maier-Moore, Jacen S.; Lessard, Christopher J.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Hefner, Kimberly S.] Hefner Eye Care & Opt Ctr, Oklahoma City, OK USA. [Anaya, Juan-Manuel] Univ Nacl Rosario, Corp Invest Biol, Bogota, Colombia. [Rohrer, Michael; Hughes, Pamela; Rhodus, Nelson L.] Univ Minnesota, Minneapolis, MN USA. [Chodosh, James] Harvard Clin & Translat Sci Ctr, Boston, MA USA. [Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Harley, John B.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA. [Segal, Barbara M.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. [Farris, A. Darise; Scofield, R. Hal] Oklahoma Med Res Foun, Oklahoma City, OK USA. RI Anaya, Juan-Manuel/J-1960-2016 OI Anaya, Juan-Manuel/0000-0002-6444-1249 NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 2203 BP S931 EP S931 PG 1 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748305123 ER PT J AU Schmajuk, G Miao, YH Yazdany, J Margaretten, M Steinman, M AF Schmajuk, Gabriela Miao, Yinghui Yazdany, Jinoos Margaretten, Mary Steinman, Michael TI Liver Toxicity Monitoring and Its Impact On Methotrexate Discontinuation in a National Cohort of Veterans SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Schmajuk, Gabriela; Margaretten, Mary] UCSF, San Francisco, CA USA. [Miao, Yinghui; Steinman, Michael] San Francisco VA Med Ctr, San Francisco, CA USA. [Yazdany, Jinoos] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 1822 BP S775 EP S775 PG 1 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748304099 ER PT J AU Sekine, H Machida, T Sakamoto, N Suzuki, E Zhang, X Reilly, C Gilkeson, GS AF Sekine, Hidemaru Machida, Takeshi Sakamoto, Natsumi Suzuki, Eiji Zhang, Xian Reilly, Christopher Gilkeson, Gary S. TI IRF-1 Deficient Lupus-Prone MRL/Lpr Mice Show Reduced Glomerulonephritis but Develop Severe Interstitial Nephritis, Renal Vasculitis and Pulmonary Granulomas with Propensity for Th2 Polarity. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Sekine, Hidemaru; Machida, Takeshi; Sakamoto, Natsumi] Fukushima Med Univ, Fukushima, Japan. [Suzuki, Eiji; Zhang, Xian; Gilkeson, Gary S.] Med Univ S Carolina, Charleston, SC 29425 USA. [Zhang, Xian] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Reilly, Christopher] Virginia Tech, Blacksburg, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 1442 BP S619 EP S620 PG 2 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748303163 ER PT J AU Tjarnlund, A Bottai, M Rider, LG Werth, VP Pilkington, CA de Visser, M Alfredsson, L Amato, AA Barohn, RJ Liang, MH Singh, JA Miller, FW Lundberg, IE AF Tjarnlund, Anna Bottai, Matteo Rider, Lisa G. Werth, Victoria P. Pilkington, Clarissa A. de Visser, Marianne Alfredsson, Lars Amato, Anthony A. Barohn, Richard J. Liang, Matthew H. Singh, Jasvinder A. Miller, Frederick W. Lundberg, Ingrid E. CA Int Myositis Classification Criter TI Progress Report On Development of Classification Criteria for Adult and Juvenile Idiopathic Inflammatory Myopathies. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Tjarnlund, Anna] Karolinska Univ Hosp, Dept Med, Rheumatol Unit, Solna, Sweden. [Bottai, Matteo; Alfredsson, Lars] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden. [Rider, Lisa G.; Miller, Frederick W.] NIEHS, NIH, Bethesda, MD USA. [Werth, Victoria P.] Univ Penn, Philadelphia, PA 19104 USA. [Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Pilkington, Clarissa A.] Great Ormond St Hosp Sick Children, London WC1N 3JH, England. [de Visser, Marianne] Univ Amsterdam, Acad Med Ctr, Dept Neurol, NL-1105 AZ Amsterdam, Netherlands. [Amato, Anthony A.; Liang, Matthew H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Amato, Anthony A.] Harvard Univ, Sch Med, Boston, MA USA. [Barohn, Richard J.] Univ Kansas, Med Ctr, Dept Neurol, Kansas City, MO USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham, AL USA. NR 0 TC 4 Z9 4 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 753 BP S323 EP S324 PG 2 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748301290 ER PT J AU Tomasson, G Monach, PA Tanriverdi, K Specks, U Stone, JH Ding, LN Fervenza, F Hoffman, GS Kallenberg, CGM Langford, CA Phippard, DJ Seo, P Spiera, RF St Clair, EW Tchao, N Freedman, JE Merkel, PA AF Tomasson, Gunnar Monach, Paul A. Tanriverdi, Kahraman Specks, Ulrich Stone, John H. Ding, Linna Fervenza, Fernando Hoffman, Gary S. Kallenberg, Cees G. M. Langford, Carol A. Phippard, Deborah J. Seo, Philip Spiera, Robert F. St Clair, E. William Tchao, Nadia Freedman, Jane E. Merkel, Peter A. TI Predictive Value of Selected Markers of Inflammation and Platelet Activation for Complete Remission in ANCA-Associated Vasculitis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Tomasson, Gunnar] Univ Iceland, Reykjavik, Iceland. [Monach, Paul A.] Boston Univ, Boston, MA 02215 USA. [Tanriverdi, Kahraman; Freedman, Jane E.] Univ Massachusetts, Wochester, MA USA. [Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Specks, Ulrich; Fervenza, Fernando] Mayo Clin, Rochester, MN USA. [Ding, Linna] NIAID, Bethesda, MD 20892 USA. [Hoffman, Gary S.; Langford, Carol A.] Cleveland Clin, Cleveland, OH 44106 USA. [Kallenberg, Cees G. M.] Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Phippard, Deborah J.; Tchao, Nadia] Immune Tolerance Network, Bethesda, MD USA. [Seo, Philip] Johns Hopkins Vasculitis Ctr, Baltimore, MD USA. [Spiera, Robert F.] Hosp Special Surg, New York, NY 10021 USA. [St Clair, E. William] Duke Univ, Med Ctr, Durham, NC USA. [Merkel, Peter A.] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 2567 BP S1085 EP S1086 PG 2 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748306077 ER PT J AU Tomasson, G Davis, JC Hoffman, GS McCune, WJ Specks, U Spiera, RF St Clair, EW Stone, JH Merkel, PA AF Tomasson, Gunnar Davis, John C., Jr. Hoffman, Gary S. McCune, W. Joseph Specks, Ulrich Spiera, Robert F. St Clair, E. William Stone, John H. Merkel, Peter A. TI Patient Global Assessments for Disease Activity Are Predictive of Future Flare in Granulomatosis with Polyangiitis (Wegener's). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Tomasson, Gunnar] Univ Iceland, Reykjavik, Iceland. [Davis, John C., Jr.] Genentech Inc, San Francisco, CA 94080 USA. [Hoffman, Gary S.] Cleveland Clin, Cleveland, OH 44106 USA. [McCune, W. Joseph] Univ Michigan, Ann Arbor, MI 48109 USA. [Specks, Ulrich] Mayo Clin, Rochester, MN USA. [Spiera, Robert F.] Hosp Special Surg, New York, NY 10021 USA. [St Clair, E. William] Duke Univ, Med Ctr, Durham, NC USA. [Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Merkel, Peter A.] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 1527 BP S654 EP S654 PG 1 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748303248 ER PT J AU Verma, SM Okawa, J Propert, K Werth, VP AF Verma, Saroj M. Okawa, Joyce Propert, Kathleen Werth, Victoria P. TI The Impact of Dyspigmentation and Scarring in Cutaneous Lupus On Quality of Life. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Okawa, Joyce] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Okawa, Joyce; Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 947 BP S411 EP S411 PG 1 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748302023 ER PT J AU Wallace, ZS Carruthers, M Khosroshahi, A Carruthers, R Shinagare, S Stemmer-Rachamimov, A Deshpande, V Stone, JH AF Wallace, Zachary S. Carruthers, Mollie Khosroshahi, Arezou Carruthers, Robert Shinagare, Shweta Stemmer-Rachamimov, Anat Deshpande, Vikram Stone, John H. TI Hypertrophic Pachymeningitis: IgG4-Related Disease Is A Common Etiology. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Wallace, Zachary S.; Carruthers, Mollie; Khosroshahi, Arezou; Carruthers, Robert; Shinagare, Shweta; Stemmer-Rachamimov, Anat; Deshpande, Vikram; Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 2528 BP S1067 EP S1068 PG 2 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748306038 ER PT J AU Yomogida, K Chou, YK Chu, CQ AF Yomogida, Kentaro Chou, Yuan K. Chu, Cong-Qiu TI Superantigen Induces IL-17 Production From Extremely Polarized Th1 Clones SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Yomogida, Kentaro; Chou, Yuan K.; Chu, Cong-Qiu] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Chu, Cong-Qiu] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 2320 BP S980 EP S980 PG 1 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748305240 ER PT J AU Zhu, XX Qiu, JH Liu, Q Liang, MR Zou, HJ AF Zhu, Xiaoxia Qiu, Jianhua Liu, Qiong Liang, Minrui Zou, Hejian TI Activation of Sirt1 Attenuates Bleomycin Induced Scleroderma Through Inhibiting Mammalian Target of Rapamycin Activation SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Scientific Meeting of the American-College-of-Rheumatology (ACR) and Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 09-14, 2012 CL Washington, DC SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Zhu, Xiaoxia] Fudan Univ, Huashan Hosp, Shanghai 200433, Peoples R China. [Qiu, Jianhua] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Ctr, Boston, MA USA. [Liu, Qiong] Fudan Univ, Inst Rheumatol Immunol & Allergy, Shanghai Med Coll, Shanghai 200433, Peoples R China. [Liang, Minrui] Fudan Univ, Huashan Hosp, Shanghai 200433, Peoples R China. [Zou, Hejian] Huashan Hosp, Shanghai, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 SU S MA 1497 BP S642 EP S642 PG 1 WC Rheumatology SC Rheumatology GA 019OD UT WOS:000309748303218 ER PT J AU Schanker, BD AF Schanker, Benjamin D. TI Epigenetic regulation of brain-derived neurotrophic factor: Implications in neurodevelopment and behavior SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material ID VAL66MET POLYMORPHISM; BDNF; DISORDERS; EPISTASIS AB Several recent research findings have implicated brain-derived neurotrophic factor (BDNF) as a mediator of neuronal plasticity. The BDNF gene is under extensive epigenetic regulation, which modulates how much or how little environmental experiences become encoded within neurons and neural circuits. Future scientific progress within the postgenomic paradigm requires elucidation of the functional trajectory in neogenetic and environment interactions. C1 [Schanker, Benjamin D.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02115 USA. [Schanker, Benjamin D.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Schanker, BD (reprint author), Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02115 USA. EM bdschanker@gmail.com NR 16 TC 2 Z9 2 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0140-525X EI 1469-1825 J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD OCT PY 2012 VL 35 IS 5 BP 377 EP 378 DI 10.1017/S0140525X12001100 PG 2 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA 026WU UT WOS:000310314600057 PM 23095399 ER PT J AU Sloan, DM Marx, BP Bovin, MJ Feinstein, BA Gallagher, MW AF Sloan, Denise M. Marx, Brian P. Bovin, Michelle J. Feinstein, Brian A. Gallagher, Matthew W. TI Written exposure as an intervention for PTSD: A randomized clinical trial with motor vehicle accident survivors SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE Trauma; PTSD; Clinical trial; Exposure treatment; Motor vehicle accident ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE-PROCESSING THERAPY; PROLONGED EXPOSURE; IMAGINAL EXPOSURE; BEHAVIOR THERAPY; TRAUMATIC EVENT; FOLLOW-UP; PSYCHOTHERAPY; DISCLOSURE; VICTIMS AB The present study examined the efficacy of a brief, written exposure therapy (WET) for posttraumatic stress disorder (PTSD). Participants were 46 adults with a current primary diagnosis of motor vehicle accident-related PTSD. Participants were randomly assigned to either WET or a waitlist (WL) condition. Independent assessments took place at baseline and 6-, 18-, and 30-weeks post baseline (WL condition not assessed at 30 weeks). Participants assigned to WET showed significant reductions in PTSD symptom severity at 6- and 18-week post-baseline, relative to WL participants, with large between-group effect sizes. In addition, significantly fewer WET participants met diagnostic criteria for PTSD at both the 6- and 18-week post-baseline assessments, relative to WL participants. Treatment gains were maintained for the WET participants at the 30-week post baseline assessment. Notably, only 9% of participants dropped out of WET and the WET participants reported a high degree of satisfaction with the treatment. These findings suggest that a brief, written exposure treatment may efficaciously treat PTSD. Future research should examine whether WET is efficacious with other PTSD samples, as well as compare the efficacy of WET with that of evidence-based treatments for PTSD. Published by Elsevier Ltd. C1 [Sloan, Denise M.; Marx, Brian P.; Bovin, Michelle J.; Gallagher, Matthew W.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. [Sloan, Denise M.; Marx, Brian P.; Bovin, Michelle J.; Gallagher, Matthew W.] Boston Univ, Sch Med, Boston, MA 02130 USA. [Feinstein, Brian A.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. RP Sloan, DM (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B2, 150 S Huntington Ave, Boston, MA 02130 USA. EM denise.sloan@gmail.com OI Sloan, Denise/0000-0002-0962-478X FU NIMH NIH HHS [R34 MH077658, R34MH077658-02] NR 50 TC 19 Z9 19 U1 1 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD OCT PY 2012 VL 50 IS 10 BP 627 EP 635 DI 10.1016/j.brat.2012.07.001 PG 9 WC Psychology, Clinical SC Psychology GA 025JZ UT WOS:000310186400006 PM 22863540 ER PT J AU Kolasinski, J Stagg, CJ Chance, SA DeLuca, GC Esiri, MM Chang, EH Palace, JA McNab, JA Jenkinson, M Miller, KL Johansen-Berg, H AF Kolasinski, James Stagg, Charlotte J. Chance, Steven A. DeLuca, Gabriele C. Esiri, Margaret M. Chang, Eun-Hyuk Palace, Jacqueline A. McNab, Jennifer A. Jenkinson, Mark Miller, Karla L. Johansen-Berg, Heidi TI A combined post-mortem magnetic resonance imaging and quantitative histological study of multiple sclerosis pathology SO BRAIN LA English DT Article DE multiple sclerosis; post-mortem imaging; diffusion imaging; white matter tracts; neurodegeneration ID APPEARING WHITE-MATTER; CLINICALLY ISOLATED SYNDROMES; CENTRAL-NERVOUS-SYSTEM; CORTICAL ATROPHY; AXONAL LOSS; COGNITIVE IMPAIRMENT; CEREBRAL-CORTEX; HUMAN THALAMUS; LESION LOAD; WALLERIAN DEGENERATION AB Multiple sclerosis is a chronic inflammatory neurological condition characterized by focal and diffuse neurodegeneration and demyelination throughout the central nervous system. Factors influencing the progression of pathology are poorly understood. One hypothesis is that anatomical connectivity influences the spread of neurodegeneration. This predicts that measures of neurodegeneration will correlate most strongly between interconnected structures. However, such patterns have been difficult to quantify through post-mortem neuropathology or in vivo scanning alone. In this study, we used the complementary approaches of whole brain post-mortem magnetic resonance imaging and quantitative histology to assess patterns of multiple sclerosis pathology. Two thalamo-cortical projection systems were considered based on their distinct neuroanatomy and their documented involvement in multiple sclerosis: lateral geniculate nucleus to primary visual cortex and mediodorsal nucleus of the thalamus to prefrontal cortex. Within the anatomically distinct thalamo-cortical projection systems, magnetic resonance imaging derived cortical thickness was correlated significantly with both a measure of myelination in the connected tract and a measure of connected thalamic nucleus cell density. Such correlations did not exist between these markers of neurodegeneration across different thalamo-cortical systems. Magnetic resonance imaging lesion analysis depicted clearly demarcated subcortical lesions impinging on the white matter tracts of interest; however, quantitation of the extent of lesion-tract overlap failed to demonstrate any appreciable association with the severity of markers of diffuse pathology within each thalamo-cortical projection system. Diffusion-weighted magnetic resonance imaging metrics in both white matter tracts were correlated significantly with a histologically derived measure of tract myelination. These data demonstrate for the first time the relevance of functional anatomical connectivity to the spread of multiple sclerosis pathology in a 'tract-specific' pattern. Furthermore, the persisting relationship between metrics from post-mortem diffusion-weighted magnetic resonance imaging and histological measures from fixed tissue further validates the potential of imaging for future neuropathological studies. C1 [Kolasinski, James; Stagg, Charlotte J.; Chang, Eun-Hyuk; Jenkinson, Mark; Miller, Karla L.; Johansen-Berg, Heidi] Univ Oxford, Ctr Funct Magnet Resonance Imaging Brain FMRIB, Oxford OX3 9DU, England. [Kolasinski, James; Stagg, Charlotte J.; Chance, Steven A.; DeLuca, Gabriele C.; Esiri, Margaret M.; Chang, Eun-Hyuk; Palace, Jacqueline A.; Johansen-Berg, Heidi] Univ Oxford, Nuffield Dept Clin Neurosci, Oxford OX3 9DU, England. [Kolasinski, James; McNab, Jennifer A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. RP Stagg, CJ (reprint author), John Radcliffe Hosp, Ctr Funct Magnet Resonance Imaging Brain, Oxford OX3 9DU, England. EM cstagg@fmrib.ox.ac.uk OI Stagg, Charlotte/0000-0002-5542-5036; Kolasinski, James/0000-0002-1599-6440; Jenkinson, Mark/0000-0001-6043-0166; Miller, Karla/0000-0002-2511-3189; Johansen-Berg, Heidi/0000-0002-4134-9730 FU Multiple Sclerosis Society; National Institute for Health Research (NIHR) Oxford Biomedical Research Centre based at Oxford University Hospitals Trust, Oxford University; Wellcome Trust; Medical Research Council FX This research was funded by The Multiple Sclerosis Society (to H.J.B.) and supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (C.J.S/H.J.B. and M. M. E.) based at Oxford University Hospitals Trust, Oxford University. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. H.J.B. holds a Wellcome Trust Senior Research Fellowship; The Medical Research Council funded the MRI scanner used for post-mortem scanning. NR 99 TC 47 Z9 47 U1 3 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD OCT PY 2012 VL 135 BP 2938 EP 2951 DI 10.1093/brain/aws242 PN 10 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 025AX UT WOS:000310156700005 PM 23065787 ER PT J AU Dhond, RP Ruzich, E Witzel, T Maeda, Y Malatesta, C Morse, LR Audette, J Hamalainen, M Kettner, N Napadow, V AF Dhond, Rupali P. Ruzich, Emily Witzel, Thomas Maeda, Yumi Malatesta, Cristina Morse, Leslie R. Audette, Joseph Haemaelaeinen, Matti Kettner, Norman Napadow, Vitaly TI Spatio-temporal mapping cortical neuroplasticity in carpal tunnel syndrome SO BRAIN LA English DT Article DE magnetoencephalography; neuropathic pain; somatosensory areas; plasticity; oscillations ID MEDIAN NERVE-STIMULATION; REGIONAL PAIN SYNDROME; PRIMARY SOMATOSENSORY CORTEX; SURFACE-BASED ANALYSIS; TACTILE STIMULATION; BRAIN ACTIVITY; COORDINATE SYSTEM; RECEPTIVE-FIELDS; ADULT MONKEYS; PHANTOM LIMB AB Neuroimaging data demonstrate that carpal tunnel syndrome, a peripheral neuropathy, is accompanied by maladaptive central neuroplasticity. To further investigate this phenomenon, we collected magnetoencephalography data from 12 patients with carpal tunnel syndrome and 12 healthy control subjects undergoing somatosensory stimulation of the median nerve-innervated Digits 2 and 3, as well as Digit 5, which is innervated by the ulnar nerve. Nerve conduction velocity and psychophysical data were acquired to determine whether standard clinical measures correlated with brain response. In subjects with carpal tunnel syndrome, but not healthy controls, sensory nerve conduction velocity for Digits 2 and 3 was slower than Digit 5. However, somatosensory M20 latencies for Digits 2 and 3 were significantly longer than those of Digit 5. The extent of the M20 delay for median nerve-innervated Digit 2 was positively correlated with decreasing nerve conduction velocity and increasing pain severity. Thus, slower peripheral nerve conduction in carpal tunnel syndrome corresponds to greater delays in the first somatosensory cortical response. Furthermore, spectral analysis demonstrated weaker post-stimulus beta event-related desynchronization and earlier and shorter event-related synchronization in subjects with carpal tunnel syndrome. The extent of the decreased event-related desynchronization for median nerve-innervated digits was positively correlated with paraesthesia severity. We propose that ongoing paraesthesias in median nerve-innervated digits render their corresponding sensorimotor cortical areas 'busy', thus reducing their capacity to process external stimulation. Finally, subjects with carpal tunnel syndrome demonstrated a smaller cortical source separation for Digits 2 and 3 compared with healthy controls. This supports our hypothesis that ongoing paraesthesias promote blurring of median nerve-innervated digit representations through Hebbian plasticity mechanisms. In summary, this study reveals significant correlation between the clinical severity of carpal tunnel syndrome and the latency of the early M20, as well as the strength of long latency beta oscillations. These temporal magnetoencephalography measures are novel markers of neuroplasticity in carpal tunnel syndrome and could be used to study central changes that may occur following clinical intervention. C1 [Dhond, Rupali P.; Ruzich, Emily; Witzel, Thomas; Maeda, Yumi; Haemaelaeinen, Matti; Napadow, Vitaly] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging,Dept Radiol, Charlestown, MA 02129 USA. [Maeda, Yumi; Kettner, Norman; Napadow, Vitaly] Logan Coll Chiropract, Dept Radiol, Chesterfield, MO 63017 USA. [Malatesta, Cristina] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Medford, MA 02155 USA. [Morse, Leslie R.] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Audette, Joseph] Atrius Hlth, Harvard Vanguard Med Associates, Dept Pain Med, Boston, MA 02215 USA. RP Dhond, RP (reprint author), MGH CNY, Martinos Ctr Biomed Imaging, Bldg 149,13th St,Room 2301, Charlestown, MA 02129 USA. EM polly@nmr.mgh.harvard.edu RI Hamalainen, Matti/C-8507-2013; Witzel, Thomas/P-1402-2014; Morse, Leslie/C-9442-2015 OI Morse, Leslie/0000-0002-7426-6341 FU National Institutes of Health NCCAM [K01AT004481, R01AT004714, P01AT002048]; NIBIB [5R01EB009048]; National Science Foundation [1042134]; National Center for Research Resources [P41RR14075]; Mental Illness and Neuroscience Discovery (MIND) Institute FX The authors thank National Institutes of Health NCCAM for funding support K01AT004481 (R. P. D.), R01AT004714 (V.N.), P01AT002048 (Rosen), NIBIB 5R01EB009048 and National Science Foundation 1042134 (M. S. H). They also acknowledge National Center for Research Resources (P41RR14075) and the Mental Illness and Neuroscience Discovery (MIND) Institute. NR 75 TC 9 Z9 9 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD OCT PY 2012 VL 135 BP 3062 EP 3073 DI 10.1093/brain/aws233 PN 10 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 025AX UT WOS:000310156700016 PM 23043143 ER PT J AU Turner, KA Cohn, ES Koomar, J AF Turner, Karen A. Cohn, Ellen S. Koomar, Jane TI Mothering when mothers and children both have sensory processing challenges SO BRITISH JOURNAL OF OCCUPATIONAL THERAPY LA English DT Article DE Parenting; sensory defensiveness; paediatrics; sensory motor integration ID PATTERNS; FAMILIES; CULTURE; ADULTS; LIFE AB Introduction: The aim of this study was to understand the perspectives of mothers when mother and child both have sensory processing challenges, and how the mother's coping strategies for managing her sensory needs influence mothering co-occupations and parenting ideals. Method: Four mothers with sensory processing challenges participated in semi-structured interviews. Data were analysed using grounded theory principles. Findings: Mothers described managing their sensory needs while negotiating the conflicting sensory preferences of their children. Coping strategies included understanding sensory processing patterns of behaviour and structuring daily activities and the environment. Some coping strategies had secondary consequences of a ripple effect, a reverberating impact that exacerbated the challenges of unmet sensory needs and interfered with co-occupations and parenting ideals. Conclusion: Implications for mothers include understanding how their sensory processing transacts with their children's sensory preferences. Implications for practitioners include attending to the sensory processing patterns and coping strategies of both children and parents. C1 [Turner, Karen A.] Massachusetts Gen Hosp, Dept Occupat Therapy, Boston, MA 02114 USA. [Cohn, Ellen S.] Boston Univ, Sargent Coll Hlth & Rehabil Sci, Dept Occupat Therapy, Boston, MA 02215 USA. [Koomar, Jane] Spiral Fdn, Newton, MA USA. RP Turner, KA (reprint author), Massachusetts Gen Hosp, Dept Occupat Therapy, 55 Fruit St, Boston, MA 02114 USA. EM karen.huefner@gmail.com NR 20 TC 1 Z9 1 U1 0 U2 2 PU COLL OCCUPATIONAL THERAPISTS LTD PI SOUTHWARK PA 106-114 BOROUGH HIGH ST, SOUTHWARK, LONDON SE1 1LB, ENGLAND SN 0308-0226 J9 BRIT J OCCUP THER JI Br. J. Occup. Ther. PD OCT PY 2012 VL 75 IS 10 BP 449 EP 455 DI 10.4276/030802212X13496921049626 PG 7 WC Rehabilitation SC Rehabilitation GA 028BZ UT WOS:000310399100003 ER PT J AU Leong, SPL Mihm, MC Murphy, GF Hoon, DSB Kashani-Sabet, M Agarwala, SS Zager, JS Hauschild, A Sondak, VK Guild, V Kirkwood, JM AF Leong, Stanley P. L. Mihm, Martin C., Jr. Murphy, George F. Hoon, Dave S. B. Kashani-Sabet, Mohammed Agarwala, Sanjiv S. Zager, Jonathan S. Hauschild, Axel Sondak, Vernon K. Guild, Valerie Kirkwood, John M. TI Progression of cutaneous melanoma: implications for treatment SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE Melanoma; Biomarkers; Progression; Metastasis ID SENTINEL LYMPH-NODE; ISOLATED LIMB INFUSION; AMERICAN-JOINT-COMMITTEE; MICROSCOPIC TUMOR BURDEN; HIGH-MOLECULAR-WEIGHT; MALIGNANT-MELANOMA; METASTATIC MELANOMA; PROGNOSTIC-SIGNIFICANCE; CANCER METASTASIS; GENE-EXPRESSION AB The survival rates of melanoma, like any type of cancer, become worse with advancing stage. Spectrum theory is most consistent with the progression of melanoma from the primary site to the in-transit locations, regional or sentinel lymph nodes and beyond to the distant sites. Therefore, early diagnosis and surgical treatment before its spread is the most effective treatment. Recently, new approaches have revolutionized the diagnosis and treatment of melanoma. Genomic profiling and sequencing will form the basis for molecular taxonomy for more accurate subgrouping of melanoma patients in the future. New insights of molecular mechanisms of metastasis are summarized in this review article. Sentinel lymph node biopsy has become a standard of care for staging primary melanoma without the need for a more morbid complete regional lymph node dissection. With recent developments in molecular biology and genomics, novel molecular targeted therapy is being developed through clinical trials. C1 [Leong, Stanley P. L.; Kashani-Sabet, Mohammed] Sutter Pacific Med Fdn, Calif Pacific Med Ctr, Ctr Melanoma Res & Treatment, San Francisco, CA 94115 USA. [Leong, Stanley P. L.] Calif Pacific Med Ctr, Dept Surg, San Francisco, CA USA. [Hoon, Dave S. B.] John Wayne Canc Inst, Santa Monica, CA USA. [Agarwala, Sanjiv S.] St Lukes Univ Hlth Network, Dept Hematol Oncol, Bethlehem, PA USA. [Zager, Jonathan S.; Sondak, Vernon K.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Cutaneous Oncol, Tampa, FL 33682 USA. [Hauschild, Axel] Univ Kiel, Dept Dermatol, D-2300 Kiel, Germany. [Guild, Valerie] Melanoma Fdn, AIM, Richmond, CA USA. [Kirkwood, John M.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Mihm, Martin C., Jr.; Murphy, George F.] Dana Farber Brigham & Womens Canc Ctr, Ctr Melanoma Oncol, Boston, MA USA. RP Leong, SPL (reprint author), Sutter Pacific Med Fdn, Calif Pacific Med Ctr, Ctr Melanoma Res & Treatment, 2340 Clay St,2nd Floor, San Francisco, CA 94115 USA. EM leongsx@cpmcri.org OI Hoon, Dave/0000-0003-1915-3683 FU National Cancer Institute [P50CA121973] FX Acknowledgments by John Kirkwood The project described was supported by Award Number P50CA121973 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 151 TC 9 Z9 10 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD OCT PY 2012 VL 29 IS 7 BP 775 EP 796 DI 10.1007/s10585-012-9521-1 PG 22 WC Oncology SC Oncology GA 028ZO UT WOS:000310464700017 PM 22892755 ER PT J AU Flaherty, KT AF Flaherty, Keith T. TI Dividing and conquering: controlling advanced melanoma by targeting oncogene-defined subsets SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE Melanoma; Targeted therapy; BRAF; MAP kinase; Resistance ID RAF INHIBITOR RESISTANCE; METASTATIC MELANOMA; ACQUIRED-RESISTANCE; TUMOR PROGRESSION; BRAF MUTATIONS; KINASE; CANCER; VEMURAFENIB; SORAFENIB; CELLS AB For decades, therapy for advanced melanoma has lagged behind most of the cancer field owing to its intrinsic resistance to conventional cytotoxic chemotherapy and limited impact of cytokine-based immunotherapy. The opportunity to develop molecularly targeted therapy emerged with the discovery of activating mutations in BRAF, a component of the long studied MAP kinase pathway. These mutations are found in approximately 50 % of patients with regionally advanced or metastatic melanoma and appear to be one of the initiating steps in the development of primary melanoma. Additional oncogenic events, particularly those that affect tumor suppressor genes, are essential for development of invasive and metastatic melanoma. Nonetheless, mutated BRAF retains its central contribution to melanoma pathophysiology even in advanced stage disease as manifested by the remarkable antitumor effects and alteration the natural history of metastatic melanoma of selective BRAF inhibitors. After initial response, resistance commonly emerges within a few months' time and the field has focused on delineating molecular mechanisms of resistance toward the goal of improving upon the early therapeutic effects of single agent BRAF inhibition. Combination regimens are currently undergoing clinical investigation. NRAS and CKIT mutant melanoma represent the next oncogene defined melanoma subsets for which initial targeted therapy approaches are being explored, with early evidence suggesting progress with MEK and CKIT inhibitors, respectively. A considerable subset of patients have melanomas that are not defined by the presence of BRAF, NRAS, or CKIT mutations and, thus, the elucidation of the entire melanoma genome is being pursued with the hope of identifying additional therapeutic targets. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Flaherty, KT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM kflaherty@partners.org NR 46 TC 10 Z9 10 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 EI 1573-7276 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD OCT PY 2012 VL 29 IS 7 BP 841 EP 846 DI 10.1007/s10585-012-9488-y PG 6 WC Oncology SC Oncology GA 028ZO UT WOS:000310464700021 PM 22661223 ER PT J AU Chang, MH Gordon, LA Fung, HB AF Chang, Mei H. Gordon, Lori A. Fung, Horatio B. TI Boceprevir: A Protease Inhibitor for the Treatment of Hepatitis C SO CLINICAL THERAPEUTICS LA English DT Review DE boceprevir; direct-acting antiviral agent; nonstructural protein 3 serine protease inhibitor; SCH 503034 ID DIRECT-ACTING ANTIVIRALS; GENOTYPE 1 INFECTION; VIRUS NS3 PROTEASE; RESISTANCE MUTATIONS; VIRAL-HEPATITIS; POLYMERASE INHIBITORS; NAIVE PATIENTS; TELAPREVIR; THERAPY; DRUGS AB Background: Boceprevir is a protease inhibitor indicated for the treatment of chronic hepatitis C virus (HCV) genotype 1 infection in combination with peginterferon and ribavirin for treatment-naive patients and those who previously failed to improve with interferon and ribavirin treatment. Objective: This article provides an overview of the mechanism of action, pharmacologic and pharmacokinetic properties, clinical efficacy, and tolerability of boceprevir. Methods: Relevant information was identified through a search of PubMed (1990 July 2012), EMBASE (1990 July 2012), International Pharmaceutical Abstracts (1970-July 2012), and Google Scholar using the key words boceprevir, SCH 503034, non-structural protein 3 (NS3) serine protease inhibitor, and direct-acting antiviral agent (DAA). Additional information was obtained from the US Food and Drug Administration's Web site, review of the reference lists of identified articles, and posters and abstracts from scientific meetings. Results: Clinical efficacy of boceprevir was assessed in 2 Phase III trials, Serine Protease Inhibitor Therapy-2 (SPRINT-2) for treatment-naive patients and Retreatment with HCV Serine Protease Inhibitor Boceprevir and PegIntron/Rebetol 2 (RESPOND-2) for treatment-experienced patients. In SPRINT-2, patients were randomized to receive peginterferon + ribavirin (PR) or peginterferon + ribavirin + boceprevir (PRB); duration of boceprevir therapy varied from 24, 32, to 44 weeks on the basis of HCV RNA results. The primary endpoint was achievement of sustained virologic response (SVR; lower limit of detection, 9.3 IU/mL). The addition of boceprevir was shown to be superior, with overall SVR rates ranging from 63% to 66% compared with 38% with PR (P < 0.001). Results of SVR in SPRINT-2 were also reorganized to monitor SVRs in black and non-black patients. Treatment-experienced patients were assessed in RESPOND-2; however, null responders were excluded. Patients were again randomized to PR or PRB; duration of boceprevir therapy varied from 32 to 44 weeks on the basis of HCV RNA results. SVR was significantly higher in patients receiving boceprevir (59%-66% vs 21% with PR; P < 0.001). This benefit was seen in both previous nonresponders (SVR, 40%-52% vs 7% with PR), as well as previous relapsers (SVR, 69%-75% vs 29% with PR). Importantly, SVR could be attained with a shortened course of therapy in almost one half of all treated patients in SPRINT-2 (44%) and RESPOND-2 (46%). Conclusions: Boceprevir was well tolerated in clinical trials and a welcomed addition to our HCV armamentarium. (Clin Ther. 2012;34:2021-2038) Published by Elsevier HS Journals, Inc. C1 [Chang, Mei H.; Gordon, Lori A.; Fung, Horatio B.] James J Peters Vet Affairs Med Ctr, Serv Pharm, Bronx, NY 10468 USA. RP Chang, MH (reprint author), James J Peters Vet Affairs Med Ctr, Serv Pharm, 130 W Kings Bridge Rd,119, Bronx, NY 10468 USA. EM Mei.Chang2@va.gov NR 78 TC 12 Z9 13 U1 1 U2 12 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD OCT PY 2012 VL 34 IS 10 BP 2021 EP 2038 DI 10.1016/j.clinthera.2012.08.009 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 029JE UT WOS:000310490600001 PM 22975763 ER PT J AU Abtahian, F Jang, IK AF Abtahian, Farhad Jang, Ik-Kyung TI Optical coherence tomography: basics, current application and future potential SO CURRENT OPINION IN PHARMACOLOGY LA English DT Article ID DRUG-ELUTING-STENTS; ACUTE MYOCARDIAL-INFARCTION; ACUTE CORONARY SYNDROME; BARE-METAL STENTS; FRACTIONAL FLOW RESERVE; INTRAVASCULAR ULTRASOUND; NEOINTIMAL COVERAGE; PLAQUE MORPHOLOGY; STATIN THERAPY; STRUT COVERAGE AB Optical coherence tomography is a relatively novel imaging modality that utilizes light to generate high resolution images of intravascular structures. As result, OCT has rapidly become a preferred modality for imaging intracoronary structures such as coronary plaques and coronary stents. OCT is increasingly being utilized to further our understanding of intracoronary pathology and the effects of therapies both pharmacologic and procedural on the coronary vasculature. This review is intended to give an overview of the current investigational uses of OCT and its potential roles as the technology matures. C1 [Abtahian, Farhad; Jang, Ik-Kyung] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,GRB 800, Boston, MA 02114 USA. EM ijang@partners.org NR 78 TC 7 Z9 8 U1 1 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4892 J9 CURR OPIN PHARMACOL JI Curr. Opin. Pharmacol. PD OCT PY 2012 VL 12 IS 5 BP 583 EP 591 DI 10.1016/j.coph.2012.07.015 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 029EY UT WOS:000310478800012 PM 22884561 ER PT J AU Diao, HY Liu, XD Wu, ZW Kang, L Cui, GY Morimoto, J Denhardt, DT Rittling, S Iwakura, Y Uede, T Li, LJ AF Diao, Hongyan Liu, Xiangdong Wu, Zhongwen Kang, Lei Cui, Guangying Morimoto, Junko Denhardt, David T. Rittling, Susan Iwakura, Yoichiro Uede, Toshimitsu Li, Lanjuan TI Osteopontin regulates interleukin-17 production in hepatitis SO CYTOKINE LA English DT Article DE Osteopontin; IL-17; Chronic hepatitis B; Concanavalin A-induced hepatitis ID CELL-MEDIATED HEPATITIS; B-DEPENDENT PATHWAY; A-INDUCED HEPATITIS; T-CELLS; CONCANAVALIN-A; GRANULOMA-FORMATION; LIVER-INJURY; HLA SYSTEM; IN-VITRO; 2 PARTS AB The overexpression of osteopontin is associated with various inflammatory liver diseases. Interestingly, each of these diseases is also associated with IL-17 expression. Therefore, we sought to determine whether there is any mechanistic link between osteopontin and IL-17. Herein we show that IL-17 and osteopontin levels were significantly increased in patients with chronic hepatitis B. We found that IL-17 and osteopontin levels increased similarly in mice with concanavalin A-induced hepatitis. Both osteopontin- and IL-17-deficient mice were resistant to concanavalin A-induced hepatic injury. In addition, osteopontin markedly induced IL-17 expression by leukocytes (from humans and mice). This effect could be blocked by a specific antibody against osteopontin. 03 integrin (one of the osteopontin receptors) was critically involved in the induction of IL-17 production by osteopontin. Osteopontin-induced IL-17 expression was mediated through the p38. JNK, and NF-kappa B pathways. These findings suggest that osteopontin regulates IL-17 production during the pathogenesis of hepatitis and provide new evidence for the critical roles of osteopontin and IL-17 in hepatitis. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Diao, Hongyan; Wu, Zhongwen; Kang, Lei; Cui, Guangying; Li, Lanjuan] Zhejiang Univ, Affiliated Hosp 1, Coll Med, State Key Lab Diag & Treatment Infect Dis, Hangzhou 310003, Zhejiang, Peoples R China. [Liu, Xiangdong] Zhejiang Sci Tech Univ, Coll Mat & Text, Hangzhou 310018, Zhejiang, Peoples R China. [Morimoto, Junko; Uede, Toshimitsu] Hokkaido Univ, Inst Med Genet, Sapporo, Hokkaido 0600815, Japan. [Denhardt, David T.] Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ 08854 USA. [Rittling, Susan] Forsyth Inst, Boston, MA 02115 USA. [Iwakura, Yoichiro] Univ Tokyo, Inst Med Sci, Ctr Med Expt, Minato Ku, Tokyo 1088639, Japan. RP Li, LJ (reprint author), Zhejiang Univ, Affiliated Hosp 1, Coll Med, State Key Lab Diag & Treatment Infect Dis, Hangzhou 310003, Zhejiang, Peoples R China. EM toshi@igm.hokudai.ac.jp; ljli@zju.edu.cn RI XiangDong, Liu/M-9548-2015; Iwakura, Yoichiro/E-5457-2011 OI XiangDong, Liu/0000-0001-5262-0031; Iwakura, Yoichiro/0000-0002-9934-5775 FU New Century Excellent Talents [NCET-09-0686]; Science and Technology Department Foundation of Zhejiang Province [2010R10061]; Fundamental Research Funds for the Central Universities [2009QNA7033] FX This work was supported by the New Century Excellent Talents (NCET-09-0686), the Science and Technology Department Foundation of Zhejiang Province (2010R10061) and Fundamental Research Funds for the Central Universities (2009QNA7033). NR 40 TC 7 Z9 9 U1 0 U2 5 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT PY 2012 VL 60 IS 1 BP 129 EP 137 DI 10.1016/j.cyto.2012.06.287 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 024FL UT WOS:000310095000022 PM 22818182 ER PT J AU Buckle, T Kuil, J van den Berg, NS Bunschoten, A Lamb, HJ Yuan, H Josephson, L van Leeuwen, FWB AF Buckle, T. Kuil, J. van den Berg, N. S. Bunschoten, A. Lamb, H. J. Yuan, H. Josephson, L. van Leeuwen, F. W. B. TI Prediction of the feasibility of an in vivo targeted imaging approach using biomarker screening in biopsy tissue. SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Meeting Abstract CT 25th Annual Congress of the European-Association-of-Nuclear-Medicine (EANM) CY OCT 27-31, 2012 CL Milan, ITALY SP European Assoc Nucl Med (EANM) C1 [Buckle, T.; Kuil, J.; van den Berg, N. S.; Bunschoten, A.; Lamb, H. J.; van Leeuwen, F. W. B.] LUMC, Leiden, Netherlands. [Yuan, H.; Josephson, L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD OCT PY 2012 VL 39 SU 2 MA OP442 BP S243 EP S243 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 019GW UT WOS:000309726600322 ER PT J AU Jacobson, AF Friedman, NC Matsuoka, DT AF Jacobson, A. F. Friedman, N. C. Matsuoka, D. T. TI Assessing the Relative Contribution of Free and Bound Radioiodine to Thyroid Visualization in I-123-MIBG Imaging SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Meeting Abstract CT 25th Annual Congress of the European-Association-of-Nuclear-Medicine (EANM) CY OCT 27-31, 2012 CL Milan, ITALY SP European Assoc Nucl Med (EANM) C1 [Jacobson, A. F.; Matsuoka, D. T.] GE Healthcare, Princeton, NJ USA. [Friedman, N. C.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD OCT PY 2012 VL 39 SU 2 MA P1070 BP S595 EP S596 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 019GW UT WOS:000309726603397 ER PT J AU Treves, ST Vija, AH Bhattacharya, M Ding, X Markelewicz, RJ Vitello, M Cao, X Zurakowski, D Zukotynski, KA Grant, FD Drubach, LA Bar-Sever, Z Gelfand, MJ AF Treves, S. T. Vija, A. H. Bhattacharya, M. Ding, X. Markelewicz, R. J. Vitello, M. Cao, X. Zurakowski, D. Zukotynski, K. A. Grant, F. D. Drubach, L. A. Bar-Sever, Z. Gelfand, M. J. TI Beyond Dose Guidelines: Lower Minimum Radiopharmaceutical Administered Doses in Pediatric Hepatobiliary Scintigraphy: Application of Enhanced Planar Processing. SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Meeting Abstract CT 25th Annual Congress of the European-Association-of-Nuclear-Medicine (EANM) CY OCT 27-31, 2012 CL Milan, ITALY SP European Assoc Nucl Med (EANM) C1 [Treves, S. T.; Vitello, M.; Cao, X.; Zurakowski, D.; Grant, F. D.; Drubach, L. A.] Childrens Hosp, Boston, MA 02115 USA. [Vija, A. H.; Bhattacharya, M.; Ding, X.] Siemens Med Solut USA Inc, Hoffman Estates, IL USA. [Markelewicz, R. J.] Harvard Univ, Sch Med, Boston, MA USA. [Zukotynski, K. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bar-Sever, Z.] Schneider Childrens Med Ctr Israel, Petah Tiqwa, Israel. [Gelfand, M. J.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD OCT PY 2012 VL 39 SU 2 MA OP418 BP S237 EP S237 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 019GW UT WOS:000309726600298 ER PT J AU Raffetto, JD AF Raffetto, Joseph D. TI Commentary on: 'In Vitro Identification of Distinctive Metabolic Signatures of Intact Varicose Vein Tissue via Magic Angle Spinning Nuclear Magnetic Resonance Spectroscopy' SO EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY LA English DT Editorial Material ID SMOOTH-MUSCLE-CELLS; COLLAGEN TYPE-III; EXTRACELLULAR-MATRIX; RISK-FACTORS; METALLOPROTEINASES; WALL C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Raffetto, JD (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. EM joseph.raffetto@med.va.gov NR 13 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1078-5884 J9 EUR J VASC ENDOVASC JI Eur. J. Vasc. Endovasc. Surg. PD OCT PY 2012 VL 44 IS 4 BP 451 EP 451 DI 10.1016/j.ejvs.2012.07.001 PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 028HB UT WOS:000310412300017 PM 22835766 ER PT J AU Tang, M Foo, J Gonen, M Guilhot, J Mahon, FX Michor, F AF Tang, Min Foo, Jasmine Goenen, Mithat Guilhot, Joelle Mahon, Francois-Xavier Michor, Franziska TI Selection pressure exerted by imatinib therapy leads to disparate outcomes of imatinib discontinuation trials SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE chronic myeloid leukemia; mathematical modeling; biostatistics; targeted therapy; minimal residual disease ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; COMPLETE MOLECULAR REMISSION; STOCHASTIC GENE-EXPRESSION; TYROSINE KINASE; STEM-CELLS; MESYLATE; CML; INHIBITOR AB Background Chronic myeloid leukemia is successfully managed by imatinib therapy, but the question remains whether treatment must be administered indefinitely. Imatinib discontinuation trials have led to two distinct outcomes: about 60% of patients experienced disease relapse within 6 months of treatment cessation, while the remaining 40% remained disease-free throughout the duration of follow-up. We aimed to investigate the mechanisms underlying these disparate clinical outcomes. Design and Methods We utilized molecular data from the "Stop Imatinib" trial together with a mathematical framework of chronic myeloid leukemia, based on a four- compartment model that can explain the kinetics of the molecular response to imatinib. This approach was complemented by statistical analyses to estimate system parameters and investigate whether chronic myeloid leukemia can be cured by imatinib therapy alone. Results We found that there are insufficient follow-up data from the "Stop Imatinib" trial in order to conclude whether the absence of a relapse signifies cure of the disease. We determined that selection of less aggressive leukemic phenotypes by imatinib therapy recapitulates the trial outcomes. This postulated mechanism agrees with the observation that most patients who have a complete molecular response after discontinuation of imatinib continue to harbor minimal residual disease, and might work in concert with other factors suppressing leukemic cell expansion when the tumor burden remains low. Conclusions Our analysis provides evidence for a mechanistic model of chronic myeloid leukemia selection by imatinib treatment and suggests that it may not be safe to discontinue therapy outside a clinical trial. C1 [Tang, Min; Michor, Franziska] Dana Farber Canc Inst, Dept Biostatist & Computat Biol, Boston, MA 02115 USA. [Tang, Min; Michor, Franziska] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Foo, Jasmine] Univ Minnesota, Sch Math, Minneapolis, MN 55455 USA. [Goenen, Mithat] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Guilhot, Joelle] CHU Poitiers, INSERM Ctr Invest Clin CIC 0802, Poitiers, France. [Mahon, Francois-Xavier] CHU Bordeaux, Hematol Lab, Bordeaux, France. [Mahon, Francois-Xavier] CHU Bordeaux, Serv Malad Sang, Bordeaux, France. [Mahon, Francois-Xavier] Univ Victor Segalen Bordeaux 2, Bordeaux, France. [Mahon, Francois-Xavier] INSERM, U876, Bordeaux, France. RP Michor, F (reprint author), Dana Farber Canc Inst, Dept Biostatist & Computat Biol, Boston, MA 02115 USA. EM francois-xavier.mahon@u-bordeaux2.fr; michor@jimmy.harvard.edu FU NCI [R01CA138234, U54CA143798] FX this work was supported by NCI grants R01CA138234 (MT, MG and FM) and U54CA143798 (JF, MG and FM). NR 31 TC 17 Z9 18 U1 0 U2 3 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD OCT PY 2012 VL 97 IS 10 BP 1553 EP 1561 DI 10.3324/haematol.2012.062844 PG 9 WC Hematology SC Hematology GA 025QZ UT WOS:000310208400019 PM 22419579 ER PT J AU Puppa, G Senore, C Sheahan, K Vieth, M Lugli, A Zlobec, I Pecori, S Wang, LM Langner, C Mitomi, H Nakamura, T Watanabe, M Ueno, H Chasle, J Conley, SA Herlin, P Lauwers, GY Risio, M AF Puppa, Giacomo Senore, Carlo Sheahan, Kieran Vieth, Michael Lugli, Alessandro Zlobec, Inti Pecori, Sara Wang, Lai Mun Langner, Cord Mitomi, Hiroyuki Nakamura, Takatoshi Watanabe, Masahiko Ueno, Hideki Chasle, Jacques Conley, Stephen A. Herlin, Paulette Lauwers, Gregory Y. Risio, Mauro TI Diagnostic reproducibility of tumour budding in colorectal cancer: a multicentre, multinational study using virtual microscopy SO HISTOPATHOLOGY LA English DT Article DE colorectal cancer; reproducibility; tumour budding; virtual microscopy ID LYMPH-NODE METASTASIS; USEFUL PROGNOSTIC MARKER; TNM STAGING SYSTEM; HIGH-RISK PATIENTS; CURATIVE RESECTION; COLON-CANCER; RECTAL-CANCER; CARCINOMA; ADENOCARCINOMA; INDEX AB Aims: Despite the established prognostic relevance of tumour budding in colorectal cancer, the reproducibility of the methods reported for its assessment has not yet been determined, limiting its use and reporting in routine pathology practice. Methods and results: A morphometric system within telepathology was devised to evaluate the reproducibility of the various methods published for the assessment of tumour budding in colorectal cancer. Five methods were selected to evaluate the diagnostic reproducibility among 10 investigators, using haematoxylin and eosin (H&E) and AE1-3 cytokeratin-immunostained, whole-slide digital scans from 50 pT1-pT4 colorectal cancers. The overall interobserver agreement was fair for all methods, and increased to moderate for pT1 cancers. The intraobserver agreement was also fair for all methods and moderate for pT1 cancers. Agreement was dependent on the participants' experience with tumour budding reporting and performance time. Cytokeratin immunohistochemistry detected a higher percentage of tumour budding-positive cases with all methods compared to H&E-stained slides, but did not influence agreement levels. Conclusions: An overall fair level of diagnostic agreement for tumour budding in colorectal cancer was demonstrated, which was significantly higher in early cancer and among experienced gastrointestinal pathologists. Cytokeratin immunostaining facilitated detection of budding cancer cells, but did not result in improved interobserver agreement. C1 [Puppa, Giacomo] G Fracastoro City Hosp, Div Pathol, Verona, Italy. [Senore, Carlo] SCDO Epidemiol Tumori, AOUS Giovanni Battista, CPO Piemonte, Turin, Italy. [Sheahan, Kieran] Univ Coll Dublin, St Vincents Univ Hosp, Sch Med & Med Sci, Dept Histopathol, Dublin 2, Ireland. [Sheahan, Kieran] Univ Coll Dublin, St Vincents Univ Hosp, Sch Med & Med Sci, Ctr Colorectal Dis, Dublin 2, Ireland. [Vieth, Michael] Klinikum Bayreuth, Inst Pathol, Bayreuth, Germany. [Lugli, Alessandro; Zlobec, Inti] Univ Bern, Inst Pathol, Bern, Switzerland. [Pecori, Sara] Univ Verona, Policlin GB Rossi, Sect Anat Pathol, Dept Pathol, I-37100 Verona, Italy. [Wang, Lai Mun] John Radcliffe Hosp, Dept Cellular Pathol, Oxford OX3 9DU, England. [Langner, Cord] Med Univ Graz, Inst Pathol, Graz, Austria. [Mitomi, Hiroyuki] Juntendo Univ, Sch Med, Dept Human Pathol, Tokyo 113, Japan. [Nakamura, Takatoshi; Watanabe, Masahiko] Kitasato Univ, Sch Med, Dept Surg, Sagamihara, Kanagawa 228, Japan. [Ueno, Hideki] Natl Def Med Coll, Dept Surg, Tokorozawa, Saitama 359, Japan. [Chasle, Jacques] Francois Baclesse Comprehens Canc Ctr, Dept Pathol, Caen, France. [Conley, Stephen A.] Massachusetts Gen Hosp, Pathol Media Lab, Pathol Serv, Boston, MA 02114 USA. [Herlin, Paulette] Univ Caen, Francois Baclesse Comprehens Canc Ctr, Grp Reg Etud Canc, F-14032 Caen, France. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Gastrointestinal Pathol Serv, Boston, MA 02114 USA. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Div Surg Pathol, Boston, MA 02114 USA. [Lauwers, Gregory Y.] Harvard Univ, Sch Med, Boston, MA USA. [Risio, Mauro] Inst Canc Res & Treatment IRCC, Unit Pathol, Turin, Italy. RP Puppa, G (reprint author), G Fracastoro City Hosp, Div Pathol, Via Circonvallaz 19, I-37047 San Bonifacio, VR, Italy. EM gpuppa@yahoo.com OI Senore, Carlo/0000-0003-1023-7477 FU AIRC FX This study was supported by Dr Gregory Y. Lauwers, Gastrointestinal Pathology Service and Division of Surgical Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Part of this work was supported by AIRC (5 per Mille project). NR 52 TC 35 Z9 37 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD OCT PY 2012 VL 61 IS 4 BP 562 EP 575 DI 10.1111/j.1365-2559.2012.04270.x PG 14 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 029GC UT WOS:000310481800004 PM 22765314 ER PT J AU Hu, DJJ Shum, PP Lim, JL Cui, Y Milenko, K Wang, YX Wolinski, T AF Hu, Dora Juan Juan Shum, Perry Ping Lim, Jun Long Cui, Ying Milenko, Karolina Wang, Yixin Wolinski, Tomasz TI A Compact and Temperature-Sensitive Directional Coupler Based on Photonic Crystal Fiber Filled With Liquid Crystal 6CHBT SO IEEE PHOTONICS JOURNAL LA English DT Article DE Nematic liquid crystal (NLC); photonic crystal fiber (PCF); temperature sensor; selective infiltration ID MICROSTRUCTURED OPTICAL-FIBER; REFRACTIVE-INDEX; INTERFEROMETER; DESIGN; SENSOR AB A directional coupler structure formed by a nematic liquid crystal (NLC)-filled photonic crystal fiber (PCF) represents a promising configuration in sensing applications. Because of large refractive index difference between the NLC and silica material, the mode coupling between the NLC waveguide and the silica core is more complicated than the situation of coupling between two fundamental modes of the waveguides. Therefore, it is necessary to perform a theoretical investigation of the mode properties associated with the experimental studies of the coupling characteristics. In this paper, we present a thorough analysis, both theoretically and experimentally, of the directional coupler structure, including the mode properties, coupling characteristics, and thermal sensing properties. The temperature response of the device is experimentally measured, showing a polynomial curve in nematic phase and a linear curve in isotropic phase. The nonlinearity of the temperature response of the device in nematic phase and the linearity in isotropic phase are attributed to the temperature dependence of the refractive index of the NLC. Specifically, the sensitivity is -3.86 nm/degrees C in isotropic phase of the 6CHBT with good linearity and shows good agreement with simulation results. C1 [Shum, Perry Ping; Lim, Jun Long; Cui, Ying; Milenko, Karolina] Nanyang Technol Univ, Sch Elect & Elect Engn, Singapore 639798, Singapore. [Hu, Dora Juan Juan; Lim, Jun Long; Milenko, Karolina; Wang, Yixin] Inst Infocomm Res, RF&Opt Dept, Singapore 138632, Singapore. [Hu, Dora Juan Juan] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Shum, Perry Ping; Cui, Ying] CINTRA CNRS NTU THALES, Singapore 639798, Singapore. [Milenko, Karolina; Wolinski, Tomasz] Warsaw Univ Technol, Fac Phys, PL-00661 Warsaw, Poland. RP Shum, PP (reprint author), Nanyang Technol Univ, Sch Elect & Elect Engn, Singapore 639798, Singapore. EM shum@ieee.org RI CINTRA, UMI3288/J-9652-2012; Shum , Ping/A-5091-2011; HU, Dora Juan Juan/J-2995-2016; OI CINTRA, UMI3288/0000-0003-3579-6558; Shum , Ping/0000-0003-1391-4736; HU, Dora Juan Juan/0000-0001-8822-3900; LIM, JUN LONG/0000-0003-0994-0691 FU A*STAR, Singapore, through the SERC Thematic Strategic Research Program (TSRP) [102-152-0012] FX This work was supported in part by the A*STAR, Singapore, through the SERC Thematic Strategic Research Program (TSRP) under Grant 102-152-0012. Corresponding author: P. P. Shum (e-mail: shum@ieee.org). NR 27 TC 9 Z9 9 U1 1 U2 37 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1943-0655 EI 1943-0647 J9 IEEE PHOTONICS J JI IEEE Photonics J. PD OCT PY 2012 VL 4 IS 5 BP 2010 EP 2016 DI 10.1109/JPHOT.2012.2223662 PG 7 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 027RA UT WOS:000310369700001 ER PT J AU Oxnard, GR Morris, MJ Hodi, FS Baker, LH Kris, MG Venook, AP Schwartz, LH AF Oxnard, Geoffrey R. Morris, Michael J. Hodi, F. Stephen Baker, Laurence H. Kris, Mark G. Venook, Alan P. Schwartz, Lawrence H. TI When Progressive Disease Does Not Mean Treatment Failure: Reconsidering the Criteria for Progression SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CELL-LUNG-CANCER; RESISTANT PROSTATE-CANCER; SOFT-TISSUE SARCOMA; PHASE-II; CLINICAL-TRIALS; SOLID TUMORS; END-POINTS; ACQUIRED-RESISTANCE; RESPONSE EVALUATION; FREE SURVIVAL AB Although progression-based endpoints, such as progression-free survival, are often key clinical trial endpoints for anticancer agents, the clinical meaning of objective progression is much less certain. As scrutiny of progression-based endpoints in clinical trials increases, it should be remembered that the Response Evaluation Criteria In Solid Tumors (RECIST) progression criteria were not developed as a surrogate for survival. Now that progression-free survival has come to be an increasingly important trial endpoint, the criteria that define progression deserve critical evaluation to determine whether alternate definitions of progression might facilitate the development of stronger surrogate endpoints and more meaningful trial results. In this commentary, we review the genesis of the criteria for progression, highlight recent data that question their value as a marker of treatment failure, and advocate for several research strategies that could lay the groundwork for a clinically validated definition of disease progression in solid tumor oncology. C1 [Oxnard, Geoffrey R.; Hodi, F. Stephen] Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Oxnard, Geoffrey R.; Hodi, F. Stephen] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Morris, Michael J.; Kris, Mark G.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Morris, Michael J.; Kris, Mark G.] Weill Cornell Med Coll, New York, NY USA. [Baker, Laurence H.] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. [Baker, Laurence H.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Venook, Alan P.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Schwartz, Lawrence H.] Columbia Univ, Med Ctr, Dept Radiol, New York, NY USA. RP Oxnard, GR (reprint author), Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Dana 1234, Boston, MA 02215 USA. EM Geoffrey_Oxnard@DFCI.Harvard.edu OI Kris, Mark/0000-0002-7317-5341; Morris, Michael J./0000-0002-9454-0096 FU NCI NIH HHS [U10 CA032102] NR 55 TC 43 Z9 43 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD OCT PY 2012 VL 104 IS 20 BP 1534 EP 1541 DI 10.1093/jnci/djs353 PG 8 WC Oncology SC Oncology GA 025UN UT WOS:000310220700005 PM 22927506 ER PT J AU Reisner, AT Chen, LY Reifman, J AF Reisner, Andrew T. Chen, Liangyou Reifman, Jaques TI The association between vital signs and major hemorrhagic injury is significantly improved after controlling for sources of measurement variability SO JOURNAL OF CRITICAL CARE LA English DT Article DE Vital signs; Decision support systems; Clinical; Hemorrhage; Data interpretation; Statistical; Emergency care; Prehospital; Trauma ID MEDICAL EMERGENCY TEAM; INTENSIVE-CARE-UNIT; TRAUMA PATIENTS; BLOOD-PRESSURE; PREHOSPITAL HYPOTENSION; RESPIRATORY RATE; SHOCK INDEX; HEART-RATE; MORTALITY; TRIAGE AB Purpose: Measurement error and transient variability affect vital signs. These issues are inconsistently considered in published reports and clinical practice. We investigated the association between major hemorrhagic injury and vital signs, successively applying analytic techniques that excluded unreliable measurements, reduced transient variation, and then controlled for ambiguity in individual vital signs through multivariate analysis. Methods: Vital sign data from 671 adult prehospital trauma patients were analyzed retrospectively. Computer algorithms were used to identify and exclude unreliable data and to apply time averaging. An ensemble classifier was developed and tested by cross-validation. Primary outcome was hemorrhagic injury plus red cell transfusion. Areas under receiver operating characteristic curves (ROC AUCs) were compared by the test of DeLong et al. Results: Of initial vital signs, systolic blood pressure (BP) had the highest ROC AUC of 0.71 (95% confidence interval, 0.64-0.78). The ROC AUCs improved after excluding unreliable data, significantly for heart rate and respiratory rate but not significantly for BP. Time averaging to reduce temporal variability further increased AUCs, significantly for BP and not significantly for heart rate and respiratory rate. The ensemble classifier yielded a final ROC AUC of 0.84 (95% confidence interval, 0.80-0.89) in cross-validation. Conclusions: Techniques to reduce variability in vital sign data can lead to significantly improved diagnostic performance. Failure to consider such variability could significantly reduce clinical effectiveness or confound research investigations. (C) 2012 Elsevier Inc. All rights reserved. C1 [Reisner, Andrew T.; Chen, Liangyou; Reifman, Jaques] USA, Med Res & Mat Command USAMRMC, TATRC, ATTN MCMR TT, Ft Detrick, MD 21702 USA. [Reisner, Andrew T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Reisner, AT (reprint author), USA, Med Res & Mat Command USAMRMC, TATRC, ATTN MCMR TT, 504 Scott St, Ft Detrick, MD 21702 USA. EM areisner@partners.org; lchen@bioanalysis.org; jaques.reifman@us.army.mil FU US Army Medical Research and Materiel Command, Fort Detrick, MD; Masimo Corp. FX This work was funded by the Combat Casualty Care Research Area Directorate of the US Army Medical Research and Materiel Command, Fort Detrick, MD.; Dr Andrew Reisner participated in a customer advisory meeting for General Electric Healthcare in 2008 and has received speaking fees from Masimo Corp. Dr Reisner is a coinvestigator on a US National Institutes of Health Bioengineering Research Partnership that includes Philips Healthcare. NR 51 TC 1 Z9 1 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0883-9441 J9 J CRIT CARE JI J. Crit. Care PD OCT PY 2012 VL 27 IS 5 AR 533.e1 DI 10.1016/j.jcrc.2012.01.006 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 025PP UT WOS:000310204300044 PM 22421006 ER PT J AU Venezia, J Cassiday, PK Marini, RP Shen, ZL Buckley, EM Peters, Y Taylor, N Dewhirst, FE Tondella, ML Fox, JG AF Venezia, Jaime Cassiday, Pamela K. Marini, Robert P. Shen, Zeli Buckley, Ellen M. Peters, Yaicha Taylor, Nancy Dewhirst, Floyd E. Tondella, Maria L. Fox, James G. TI Characterization of Corynebacterium species in macaques SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article ID CUTANEOUS DIPHTHERIA; SEQUENCE-ANALYSIS; URINARY CALCULUS; ULCERANS STRAINS; UNITED-KINGDOM; IDENTIFICATION; PSEUDOTUBERCULOSIS; MICROBIOLOGY; INFECTION; RATS AB Bacteria of the genus Corynebacterium are important primary and opportunistic pathogens. Many are zoonotic agents. In this report, phenotypic (API Coryne analysis), genetic (rpoB and 16S rRNA gene sequencing), and physical methods (MS) were used to distinguish the closely related diphtheroid species Corynebacterium ulcerans and Corynebacterium pseudotuberculosis, and to definitively diagnose Corynebacterium renale from cephalic implants of rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques used in cognitive neuroscience research. Throat and cephalic implant cultures yielded 85 isolates from 43 macaques. Identification by API Coryne yielded C. ulcerans (n=74), Corynebacterium pseudotuberculosis (n=2), C. renale or most closely related to C. renale (n=3), and commensals and opportunists (n=6). The two isolates identified as C. pseudo tuberculosis by API Coryne required genetic and MS analysis for accurate characterization as C. ulcerans. Of three isolates identified as C. renale by 16S rRNA gene sequencing, only one could be confirmed as such by API Coryne, rpoB gene sequencing and MS. This study emphasizes the importance of adjunct methods in identification of coryneforms and is the first isolation of C. renale from cephalic implants in macaques. C1 [Venezia, Jaime; Marini, Robert P.; Shen, Zeli; Buckley, Ellen M.; Peters, Yaicha; Taylor, Nancy; Fox, James G.] MIT, Div Comparat Med, Cambridge, MA 02139 USA. [Cassiday, Pamela K.; Tondella, Maria L.] Ctr Dis Control & Prevent, Div Bacterial Dis, Atlanta, GA 30333 USA. [Dewhirst, Floyd E.] Forsyth Inst, Dept Mol Genet, Cambridge, MA 02142 USA. [Dewhirst, Floyd E.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Fox, JG (reprint author), MIT, Div Comparat Med, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM jgfox@mit.edu FU NIH [DE106937, T32-RR032307] FX This study was funded by NIH grant(s): DE106937 (F. E. D.); T32-RR032307 (J. G. F.). NR 34 TC 6 Z9 9 U1 0 U2 8 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-2615 J9 J MED MICROBIOL JI J. Med. Microbiol. PD OCT PY 2012 VL 61 IS 10 BP 1401 EP 1408 DI 10.1099/jmm.0.045377-0 PG 8 WC Microbiology SC Microbiology GA 028HX UT WOS:000310414500008 PM 22723254 ER PT J AU Gold, JI Douglas, MK Thomas, ML Elliott, JE Rao, SM Miaskowski, C AF Gold, Jeffrey I. Douglas, Marilyn 'Marty' K. Thomas, Mary Laudon Elliott, Janette E. Rao, Stephen M. Miaskowski, Christine TI The Relationship Between Posttraumatic Stress Disorder, Mood States, Functional Status, and Quality of Life in Oncology Outpatients SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE Cancer; posttraumatic stress disorder (PTSD); mood states; functional status; quality of life ID KARNOFSKY PERFORMANCE STATUS; CANCER PAIN MANAGEMENT; NON-HODGKINS-LYMPHOMA; BREAST-CANCER; PTSD SYMPTOMS; SURVIVORS; VETERANS; THERAPY; ADJUSTMENT; DEPRESSION AB Context. Oncology patients are at risk for developing posttraumatic stress disorder (PTSD) and other comorbid mood states, which are associated with decreases in functional status and quality of life (QOL). However, few studies have investigated the relationship between PTSD, other mood states, functional status, and QOL in oncology outpatients. Objectives. This study had four aims: 1) determine the percentages of patients with PTSD and partial PTSD; 2) evaluate for differences in demographic and clinical characteristics among patients with PTSD, partial PTSD, and no PTSD; 3) evaluate for differences in mood states, functional status, and QOL among the three PTSD groups; and 4) evaluate whether demographic and disease characteristics were predictors of PTSD. Methods. As part of a larger clinical trial that evaluated the effects of a cognitive-behavioral intervention on cancer pain management, 289 adult oncology patients (M-age = 61.3, SD = 11.6) completed self-report measures that assessed PTSD, other mood states, functional status, and QOL. Results. Forty-five percent of the sample met the diagnostic criteria for PTSD (n = 78) and partial PTSD (n = 53) and were younger than those with no PTSD. Patients with PTSD had a significantly lower Karnofsky Performance Status, shorter time since diagnosis, higher ratings of mood disturbance, lower ratings of functional status, and lower QOL than patients with no PTSD. A lower Karnofsky Performance Status, fewer months since diagnosis, and presence of bone metastases predicted a higher likelihood of being classified as having PTSD. Conclusion. Early identification and interventions may mediate the onset of psychological distress and improve health outcomes. J Pain Symptom Manage 2012;44:520-531. (C) 2012 U. S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 [Gold, Jeffrey I.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90027 USA. Childrens Hosp Los Angeles, Pain Management & Palliat Care Program, Dept Anesthesiol Crit Care Med, Los Angeles, CA 90027 USA. [Douglas, Marilyn 'Marty' K.] Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. [Douglas, Marilyn 'Marty' K.; Thomas, Mary Laudon; Elliott, Janette E.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Rao, Stephen M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Miaskowski, Christine] Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA USA. RP Gold, JI (reprint author), Univ So Calif, Childrens Hosp Los Angeles, Keck Sch Med, 4650 Sunset Blvd,MS 12, Los Angeles, CA 90027 USA. EM jgold@chla.usc.edu FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service [NRI-97026] FX This research was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (project no. NRI-97026). The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. The authors declare no conflicts of interest. NR 49 TC 5 Z9 6 U1 3 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD OCT PY 2012 VL 44 IS 4 BP 520 EP 531 DI 10.1016/j.jpainsymman.2011.10.014 PG 12 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 029QY UT WOS:000310511800007 PM 22743157 ER PT J AU Babitt, JL Lin, HY AF Babitt, Jodie L. Lin, Herbert Y. TI Mechanisms of Anemia in CKD SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC KIDNEY-DISEASE; RECOMBINANT-HUMAN-ERYTHROPOIETIN; HEMODIALYSIS-PATIENTS; EPOETIN-ALPHA; RENAL-FAILURE; HEPCIDIN; SERUM; INFLAMMATION; PEPTIDE; TRIAL AB Anemia is a common feature of CKD associated with poor outcomes. The current management of patients with anemia in CKD is controversial, with recent clinical trials demonstrating increased morbidity and mortality related to erythropoiesis stimulating agents. Here, we examine recent insights into the molecular mechanisms underlying anemia of CKD. These insights hold promise for the development of new diagnostic tests and therapies that directly target the pathophysiologic processes underlying this form of anemia. C1 [Babitt, Jodie L.; Lin, Herbert Y.] Harvard Univ, Program Anemia Signaling Res, Massachusetts Gen Hosp, Nephrol Div,Program Membrane Biol,Ctr Syst Biol,M, Boston, MA 02114 USA. RP Babitt, JL (reprint author), Harvard Univ, Program Anemia Signaling Res, Massachusetts Gen Hosp, Nephrol Div,Program Membrane Biol,Ctr Syst Biol,M, 185 Cambridge St,CPZN 8208, Boston, MA 02114 USA. EM babitt.jodie@mgh.harvard.edu; lin.her-bert@mgh.harvard.edu FU National Institutes of Health [RO1 DK087727, K08 DK-075846, RO1 DK-069533, RO1 DK-071837]; Claffin Distinguished Scholar Award from the Massachusetts General Hospital FX J.L.B. is supported in part by National Institutes of Health Grants RO1 DK087727 and K08 DK-075846 and a Claffin Distinguished Scholar Award from the Massachusetts General Hospital. H.Y.L. is supported in part by National Institutes of Health Grants RO1 DK-069533 and RO1 DK-071837. NR 41 TC 63 Z9 65 U1 4 U2 9 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 2012 VL 23 IS 10 BP 1631 EP 1634 DI 10.1681/ASN.2011111078 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 019JO UT WOS:000309736000008 PM 22935483 ER PT J AU Habib, SL Yadav, M Tizani, S Bhandari, B Valente, AJ AF Habib, Samy L. Yadav, Mukesh Tizani, Shaza Bhandari, Basant Valente, Anthony J. TI Tuberin Inhibits Production of the Matrix Protein Fibronectin in Diabetes SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID REPAIR ENZYME OGG1; MAMMALIAN TARGET; CELL-GROWTH; 3-KINASE/AKT PATHWAY; EPITHELIAL-CELLS; PROXIMAL TUBULE; HIGH GLUCOSE; SCLEROSIS; GENE; RAPAMYCIN AB Exposure of proximal tubular epithelial cells to high glucose contributes to the accumulation of tubulointerstitial and matrix proteins in diabetic nephropathy, but how this occurs is not well understood. We investigated the effect of the signaling molecule tuberin, which modulates the mammalian target of rapamycin pathway, on renal hypertrophy and fibronectin expression. We found that the kidney mass was significantly greater in partially tuberin-deficient (TSC2(+/-)) diabetic rats than wild-type diabetic rats. Furthermore, TSC2(+/-) rats exhibited significant increases in the basal levels of phospho-tuberin and fibronectin expression in the kidney cortex. Increased levels of phosphorylated tuberin associated with an increase in fibronectin expression in both wild-type and TSC2(+/-) diabetic rats. Treatment with insulin abrogated the diabetes-induced increase in fibronectin expression. In vitro, high glucose enhanced fibronectin expression in TSC2(+/-) primary proximal tubular epithelial cells; both inhibition of Akt and inhibition of the mammalian target of rapamycin could prevent this effect of glucose. In addition, forced expression of tuberin in tuberin-null cells abolished the expression of fibronectin protein. Taken together, these data suggest that tuberin plays a central role in the development of renal hypertrophy and in modulating the production of the matrix protein fibronectin in diabetes. C1 [Habib, Samy L.; Yadav, Mukesh; Tizani, Shaza] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Habib, Samy L.; Bhandari, Basant; Valente, Anthony J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Habib, Samy L.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Habib, SL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM habib@uthscsa.edu FU American Heart Association; South Texas Veterans Healthcare System FX This work was supported in part by grants from the American Heart Association and a Merit Review Award from the South Texas Veterans Healthcare System (to S.L.H.). NR 32 TC 13 Z9 15 U1 1 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 2012 VL 23 IS 10 BP 1652 EP 1662 DI 10.1681/ASN.2012030285 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 019JO UT WOS:000309736000011 PM 22904348 ER PT J AU Kao, RM Vasilyev, A Miyawaki, A Drummond, IA McMahon, AP AF Kao, Robert M. Vasilyev, Aleksandr Miyawaki, Atsushi Drummond, Iain A. McMahon, Andrew P. TI Invasion of Distal Nephron Precursors Associates with Tubular Interconnection during Nephrogenesis SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID DEVELOPING MOUSE KIDNEY; ANCHOR-CELL INVASION; PROGENITOR POPULATION; BASEMENT-MEMBRANES; MOLECULAR NETWORK; EMBRYONIC KIDNEY; PRIMARY MOUTH; C-ELEGANS; MORPHOGENESIS; EXPRESSION AB Formation of a functional renal network requires the interconnection of two epithelial tubes: the nephron, which arises from kidney mesenchyme, and the collecting system, which originates from the branching ureteric epithelium. How this connection occurs, however, is incompletely understood. Here, we used high-resolution image analysis in conjunction with genetic labeling of epithelia to visualize and characterize this process. Although the focal absence of basal lamina from renal vesicle stages ensures that both epithelial networks are closely apposed, we found that a patent luminal interconnection is not established until S-shaped body stages. Precursor cells of the distal nephron in the interconnection zone exhibit a characteristic morphology consisting of ill-defined epithelial junctional complexes but without expression of mesenchymal markers such as vimentin and Snai2. Live-cell imaging revealed that before luminal interconnection, distal cells break into the lumen of the collecting duct epithelium, suggesting that an invasive behavior is a key step in the interconnection process. Furthermore, loss of distal cell identity, which we induced by activating the Notch pathway, prevented luminal interconnection. Taken together, these data support a model in which establishing the distal identity of nephron precursor cells closest to the nascent collecting duct epithelium leads to an active cell invasion, which in turn contributes to a patent tubular interconnection between the nephron and collecting duct epithelia. C1 [Kao, Robert M.; McMahon, Andrew P.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Kao, Robert M.; McMahon, Andrew P.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Vasilyev, Aleksandr; Drummond, Iain A.] Harvard Univ, Massachusetts Gen Hosp, Div Nephrol, Cambridge, MA 02138 USA. [Miyawaki, Atsushi] RIKEN, Brain Sci Inst, Wako, Saitama, Japan. [Miyawaki, Atsushi] Japan Sci & Technol Agcy, Life Funct & Dynam, Exploratory Res Adv Technol, Wako, Saitama, Japan. [McMahon, Andrew P.] Harvard Stem Cell Inst, Cambridge, MA USA. RP McMahon, AP (reprint author), Univ So Calif, Dept Stem Cell Biol & Regenerat Med, Broad CIRM Ctr, Keck Sch Med, 1425 San Pablo St, Los Angeles, CA 90089 USA. EM amcmahon@med.usc.edu RI Miyawaki, Atsushi/K-3569-2014 OI Miyawaki, Atsushi/0000-0002-2329-3235 FU National Science Foundation [DGE-0644491, DGE-0946799]; National Institutes of Health (NIH) [K08DK082782, RO1 DK053093, R37 DK054364]; Harvard Stem Cell Institute Seed Grant FX R.K. was supported by a National Science Foundation graduate research fellowship (Grants DGE-0644491 and DGE-0946799). A.V. was supported by National Institutes of Health (NIH) Grant K08DK082782 and a Harvard Stem Cell Institute Seed Grant. I.A.D. was supported by an NIH grant (RO1 DK053093). Work in A.P.M.'s laboratory was supported by an NIH grant (R37 DK054364). NR 33 TC 14 Z9 14 U1 1 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 2012 VL 23 IS 10 BP 1682 EP 1690 DI 10.1681/ASN.2012030283 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 019JO UT WOS:000309736000014 PM 22904347 ER PT J AU Park, M Hsu, CY Li, YM Mishra, RK Keane, M Rosas, SE Dries, D Xie, DW Chen, J He, J Anderson, A Go, AS Shlipak, MG AF Park, Meyeon Hsu, Chi-yuan Li, Yongmei Mishra, Rakesh K. Keane, Martin Rosas, Sylvia E. Dries, Daniel Xie, Dawei Chen, Jing He, Jiang Anderson, Amanda Go, Alan S. Shlipak, Michael G. CA Chronic Renal Insufficiency Cohort TI Associations between Kidney Function and Subclinical Cardiac Abnormalities in CKD SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID LEFT-VENTRICULAR HYPERTROPHY; CHRONIC RENAL-INSUFFICIENCY; CONGESTIVE-HEART-FAILURE; CYSTATIN-C; DIASTOLIC FUNCTION; EJECTION FRACTION; UREMIC CARDIOMYOPATHY; SYSTOLIC FUNCTION; DISEASE PATIENTS; RISK-FACTOR AB Heart failure is a common consequence of CKD, and it portends high risk for mortality. However, among patients without known heart failure, the associations of different stages of estimated GFR (eGFR) with changes in cardiac structure and function are not well described. Here, we performed a cross-sectional analysis to study these associations among 3487 participants of the Chronic Renal Insufficiency Cohort Study. We estimated GFR using cystatin C. The prevalence of left ventricular hypertrophy (LVH) assessed by echocardiography was 32%, 48%, 57%, and 75% for eGFR categories >= 60, 45-59, 30-44, and <30 ml/min per 1.73 m(2.), respectively. In fully adjusted multivariable analyses, subjects with eGFR levels of <30 ml/min per 1.73 m(2) had twofold higher odds of LVH (OR=2.20, 95% CI=1.40-3.40; P<0.001) relative to subjects with eGFR >= 60 ml/min per 1.73 m(2). This reduction in kidney function also significantly associated with abnormal LV geometry but not diastolic or systolic dysfunction. An eGFR of 30-44 ml/min per 1.73 m(2) also significantly associated with LVH and abnormal LV geometry compared with eGFR >= 60 ml/min per 1.73 m(2). In summary, in this large CKD cohort, reduced kidney function associated with abnormal cardiac structure. We did not detect significant associations between kidney function and systolic or diastolic function after adjusting for potential confounding variables. C1 [Park, Meyeon; Hsu, Chi-yuan] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Li, Yongmei; Shlipak, Michael G.] San Francisco VA Med Ctr, Div Gen Internal Med, San Francisco, CA USA. [Mishra, Rakesh K.] San Francisco VA Med Ctr, Div Cardiol, San Francisco, CA USA. [Keane, Martin; Dries, Daniel] Univ Penn, Sch Med, Div Cardiovasc, Philadelphia, PA 19104 USA. [Rosas, Sylvia E.] Univ Penn, Sch Med, Div Renal, Philadelphia, PA 19104 USA. [Xie, Dawei; Anderson, Amanda] Univ Penn, Dept Epidemiol, Philadelphia, PA 19104 USA. [Chen, Jing] Tulane Sch Med, Sect Nephrol & Hypertens, New Orleans, LA USA. [He, Jiang] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA. [Go, Alan S.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Go, Alan S.; Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Go, Alan S.; Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Go, Alan S.; Shlipak, Michael G.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. RP Park, M (reprint author), Univ Calif San Francisco, Div Nephrol, 521 Parnassus Ave,C443,Box 0532, San Francisco, CA 94143 USA. EM meyeon.park@ucsf.edu FU American Heart Association Western Affiliates Fellowship Grant; National Institutes of Health National Research Service Award [F32 DK093231]; Chronic Renal Insufficiency Cohort General Clinical Research Center; University of Pennsylvania [UL1 RR-024134]; Johns Hopkins University [UL1 RR-025005]; University of Maryland [M01 RR-16500]; Case Western Reserve University [UL1 RR-024989]; University of Michigan [M01 RR-000042, UL1 RR-024986]; University of Illinois at Chicago [UL1 RR-029879]; [K24 DK92291]; [R01 DK066488] FX M.P. was supported by an American Heart Association Western Affiliates Fellowship Grant and is currently supported by National Institutes of Health National Research Service Award Grant F32 DK093231. C.-y.H. was partially funded by Grant K24 DK92291. This project was supported by Grant R01 DK066488 (to M.G.S.). In addition, we would like to acknowledge the Chronic Renal Insufficiency Cohort General Clinical Research Center and Clinical and Translational Science Awards: University of Pennsylvania Grant UL1 RR-024134, Johns Hopkins University Grant UL1 RR-025005, University of Maryland Grant M01 RR-16500, Case Western Reserve University Grant UL1 RR-024989, University of Michigan Grants M01 RR-000042 and UL1 RR-024986, and University of Illinois at Chicago Grant UL1 RR-029879. NR 38 TC 66 Z9 73 U1 1 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 2012 VL 23 IS 10 BP 1725 EP 1734 DI 10.1681/ASN.2012020145 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 019JO UT WOS:000309736000018 PM 22935481 ER PT J AU Harb, GC Thompson, R Ross, RJ Cook, JM AF Harb, Gerlinde C. Thompson, Richard Ross, Richard J. Cook, Joan M. TI Combat-Related PTSD Nightmares and Imagery Rehearsal: Nightmare Characteristics and Relation to Treatment Outcome SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; SEXUAL ASSAULT SURVIVORS; SLEEP DISTURBANCE; EXPOSURE THERAPY; DREAM CONTENT; VETERANS; SYMPTOM; TRAUMA AB The characteristics of nightmares of 48 male U.S. Vietnam war veterans with combat-related posttraumatic stress disorder (PTSD), as well as revised dream scripts developed in the course of Imagery Rehearsal therapy, were examined in relation to pretreatment symptomatology and treatment outcome. Features, content, and themes of nightmares and rescripted dreams were coded by 2 independent raters. Nightmares were replete with scenes of death and violence and were predominantly replays of actual combat events in which the veteran was under attack and feared for his life. Although addressing or resolving the nightmare theme with rescripting was associated with a reduction in sleep disturbance, references to violence in the rescripted dream were related to poorer treatment outcome in nightmare frequency; B = 5.69 (SE = 1.14). The experience of olfactory sensations in nightmares, a possible index of nightmare intensity, was also related to poorer treatment response; B = 2.95 (SE = 1.06). Imagery rehearsal for individuals with severe, chronic PTSD and fairly replicative nightmares may be most effective when the rescripted dream incorporates a resolution of the nightmare theme and excludes violent details. C1 [Thompson, Richard] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. [Ross, Richard J.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Cook, Joan M.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Cook, Joan M.] Natl Ctr PTSD, Evaluat Div, West Haven, CT USA. [Harb, Gerlinde C.; Ross, Richard J.] Philadelphia VA Med Ctr, Behav Hlth Serv Res, Philadelphia, PA USA. RP Cook, JM (reprint author), Yale Univ, Sch Med, NEPEC 182,950 Campbell Ave, West Haven, CT 06516 USA. EM Joan.Cook@yale.edu NR 37 TC 6 Z9 6 U1 5 U2 22 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2012 VL 25 IS 5 BP 511 EP 518 DI 10.1002/jts.21748 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 026CV UT WOS:000310251500004 PM 23047646 ER PT J AU Monson, CM Macdonald, A Vorstenbosch, V Shnaider, P Goldstein, ESR Ferrier-Auerbach, AG Mocciola, KE AF Monson, Candice M. Macdonald, Alexandra Vorstenbosch, Valerie Shnaider, Philippe Goldstein, Elizabeth S. R. Ferrier-Auerbach, Amanda G. Mocciola, Katharine E. TI Changes in Social Adjustment With Cognitive Processing Therapy: Effects of Treatment and Association With PTSD Symptom Change SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; MALE VIETNAM VETERANS; QUALITY-OF-LIFE; FUNCTIONAL IMPAIRMENT; CHILDHOOD ABUSE; SEXUAL ASSAULT; SELF-REPORT; AVOIDANCE; SURVIVORS; EXPOSURE AB The current study sought to determine if different spheres of social adjustment, social and leisure, family, and work and income improved immediately following a course of cognitive processing therapy (CPT) when compared with those on a waiting list in a sample of 46 U.S. veterans diagnosed with posttraumatic stress disorder (PTSD). We also sought to determine whether changes in different PTSD symptom clusters were associated with changes in these spheres of social adjustment. Overall social adjustment, extended family relationships, and housework completion significantly improved in the CPT versus waiting-list condition, ?2 = .08 to .11. Hierarchical multiple regression analyses revealed that improvements in total clinician-rated PTSD symptoms were associated with improvements in overall social and housework adjustment. When changes in reexperiencing, avoidance, emotional numbing, and hyperarousal were all in the model accounting for changes in total social adjustment, improvements in emotional numbing symptoms were associated with improvements in overall social, extended family, and housework adjustment (beta = .38 to .55). In addition, improvements in avoidance symptoms were associated with improvements in housework adjustment (beta= .30), but associated with declines in extended family adjustment (beta = -.34). Results suggest that it is important to consider the extent to which PTSD treatments effectively reduce specific types of symptoms, particularly emotional numbing and avoidance, to generally improve social adjustment. C1 [Monson, Candice M.; Vorstenbosch, Valerie; Shnaider, Philippe] Ryerson Univ, Dept Psychol, Toronto, ON M5B 2K3, Canada. [Monson, Candice M.; Macdonald, Alexandra] US VA Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA. [Vorstenbosch, Valerie] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Goldstein, Elizabeth S. R.] US VA Natl Ctr PTSD, Execut Div, White River Jct, VT USA. [Ferrier-Auerbach, Amanda G.] Minneapolis VA Healthcare Syst, Mental Hlth Serv, Minneapolis, MN USA. [Ferrier-Auerbach, Amanda G.] Univ Minnesota, Sch Med, Dept Psychiat, Minneapolis, MN 55455 USA. [Mocciola, Katharine E.] US VA Maine Healthcare Syst, Mental Hlth Serv, Augusta, ME USA. [Macdonald, Alexandra] Boston Univ, Dept Psychiat, Boston, MA 02215 USA. [Goldstein, Elizabeth S. R.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Psychiat, Hanover, NH 03756 USA. RP Monson, CM (reprint author), Ryerson Univ, Dept Psychol, 350 Victoria St, Toronto, ON M5B 2K3, Canada. EM candice.monson@psych.ryerson.ca NR 35 TC 8 Z9 8 U1 2 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2012 VL 25 IS 5 BP 519 EP 526 DI 10.1002/jts.21735 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 026CV UT WOS:000310251500005 PM 23073971 ER PT J AU Hellmuth, JC Stappenbeck, CA Hoerster, KD Jakupcak, M AF Hellmuth, Julianne C. Stappenbeck, Cynthia A. Hoerster, Katherine D. Jakupcak, Matthew TI Modeling PTSD Symptom Clusters, Alcohol Misuse, Anger, and Depression as They Relate to Aggression and Suicidality in Returning US Veterans SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; AFGHANISTAN WAR VETERANS; COGNITIVE-BEHAVIORAL THERAPY; VIETNAM COMBAT VETERANS; PRIMARY-CARE; MILITARY VETERANS; IRAQ; IDEATION; VIOLENCE; RISK AB Suicidal ideation and aggression are common correlates of posttraumatic stress disorder (PTSD) among U.S. Iraq and Afghanistan war veterans. The existing literature has established a strong link between these factors, but a more nuanced understanding of how PTSD influences them is needed. The current study examined the direct and indirect relationships between PTSD symptom clusters and suicidal ideation in general aggression (without a specified target) regarding depression, alcohol misuse, and trait anger. Participants were 359 (92% male) U.S. Iraq/Afghanistan war veterans. Path analysis results suggested that the PTSD numbing cluster was directly (beta= .28, p< .01) and indirectly (beta= .17, p= .001) related through depression. The PTSD hyperarousal cluster was indirectly related to suicidal ideation through depression (beta= .13, p< .001). The PTSD reexperiencing cluster was directly related to aggression (beta= .17, p< .05), whereas the PTSD numbing and hyperarousal clusters were indirectly related to aggression through trait anger (beta= .05, p< .05; beta= .20, p< .001). These findings indicate that adjunct treatments aimed at stabilizing anger, depression, and alcohol misuse may help clinicians ameliorate the maladaptive patterns often observed in veterans. These results also point to specific manifestations of PTSD and co-occurring conditions that may inform clinicians in their attempts to identify at risk veterans and facilitate preventative interventions. C1 [Hoerster, Katherine D.; Jakupcak, Matthew] VA Puget Sound Hlth Care Syst, MIRECC, Seattle, WA USA. RP Hellmuth, JC (reprint author), Dept Psychiat, Div Prevent & Community Res, 389 Whitney Ave, New Haven, CT 06511 USA. EM Julianne.Hellmuth@yale.edu FU NIDA NIH HHS [T32 DA019426, T32DA019426] NR 52 TC 32 Z9 32 U1 3 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2012 VL 25 IS 5 BP 527 EP 534 DI 10.1002/jts.21732 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 026CV UT WOS:000310251500006 PM 23073972 ER PT J AU Mitchell, KS Wells, SY Mendes, A Resick, PA AF Mitchell, Karen S. Wells, Stephanie Y. Mendes, Adell Resick, Patricia A. TI Treatment Improves Symptoms Shared by PTSD and Disordered Eating SO JOURNAL OF TRAUMATIC STRESS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; MEDIATING ROLE; VALIDATION; SCALE; DYSREGULATION; ALEXITHYMIA; COMORBIDITY; INVENTORY; NERVOSA; OBESITY AB Eating disorders and posttraumatic stress disorder (PTSD) are debilitating conditions that frequently co-occur. Although the two disorders have different clinical presentations, they share associated features, including cognitive disturbances, emotion dysregulation, dissociation, and impulsivity. We hypothesized that reductions in PTSD symptoms following cognitive processing therapy (CPT) and its treatment components (CPT without the written account or the written account only) would be associated with improvements in symptoms common to PTSD and eating disorders. Participants in the current investigation included women with PTSD (N = 65) who reported a history of rape or physical assault, were in a randomized dismantling study of CPT, and completed the Eating Disorder Inventory-2 (EDI-2) at pre- and posttreatment. Latent growth modeling results indicated that decreases in PTSD symptom scores were significantly associated with reductions in the Impulse Regulation, Interoceptive Awareness, Interpersonal Distrust, Ineffectiveness, and Maturity Fears subscales of the EDI-2. Thus, PTSD treatment affected symptoms shared by PTSD and eating disorders. Currently, there are no clear guidelines for treatment of comorbid PTSD and eating disorders. Traditional CPT may impact symptoms common to both, but additional therapy may be needed for specific disordered eating attitudes and behaviors. C1 [Mitchell, Karen S.; Resick, Patricia A.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Mitchell, Karen S.; Wells, Stephanie Y.; Mendes, Adell; Resick, Patricia A.] VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA. RP Mitchell, KS (reprint author), VA Boston Healthcare Syst, WHSD 116B 3, 150 S Huntington Ave, Boston, MA 02130 USA. EM ksmitche@bu.edu FU NIMH NIH HHS [R01-MH51509] NR 37 TC 3 Z9 3 U1 5 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2012 VL 25 IS 5 BP 535 EP 542 DI 10.1002/jts.21737 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 026CV UT WOS:000310251500007 PM 23073973 ER PT J AU Bunnell, C AF Bunnell, Craig TI Integrating Value Assessment Into Discussions About the Price of Cancer Drugs SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material ID COST; THERAPIES; CARE C1 Dana Farber Canc Inst, Boston, MA 02215 USA. RP Bunnell, C (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM craig_.bunnell@dfci.harvard.edu NR 13 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD OCT PY 2012 VL 87 IS 10 BP 932 EP 934 DI 10.1016/j.mayocp.2012.08.009 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 024QE UT WOS:000310122900002 PM 23036668 ER PT J AU Vasdev, N Cao, PP van Oosten, EM Wilson, AA Houle, S Hao, GY Sun, XK Slavine, N Alhasan, M Antich, PP Bonte, FJ Kulkarni, P AF Vasdev, Neil Cao, Pengpeng van Oosten, Erik M. Wilson, Alan A. Houle, Sylvain Hao, Guiyang Sun, Xiankai Slavine, Nikolai Alhasan, Mustafa Antich, Peter P. Bonte, Frederick J. Kulkarni, Padmakar TI Synthesis and PET imaging studies of [F-18]2-fluoroquinolin-8-ol ([F-18]CABS13) in transgenic mouse models of Alzheimer's disease SO MEDCHEMCOMM LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; AMYLOID-BETA; BRAIN; THERAPEUTICS; HYPOTHESIS; CLIOQUINOL; DEMENTIA; METALS; IRON AB Benzyloxy-2-chloroquinoline was reacted with fluorine-18 labelled potassium cryptand fluoride, followed by catalytic hydrogenation to prepare [F-18]2-fluoroquinolin-8-ol in high radiochemical yields (30%; uncorrected and relative to [F-18]-fluoride), specific activities (>1 Ci mu mol(-1)) and radiochemical purities (>99%) within 70 min; PET-CT imaging with this new radiotracer in double transgenic mice shows excellent promise for imaging Alzheimer's disease. C1 [Vasdev, Neil] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging Radiol, Boston, MA 02114 USA. [Vasdev, Neil] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Vasdev, Neil; Wilson, Alan A.; Houle, Sylvain] Univ Toronto, Dept Psychiat, Toronto, ON M5T 1R8, Canada. [Vasdev, Neil; Cao, Pengpeng; van Oosten, Erik M.; Wilson, Alan A.; Houle, Sylvain] Ctr Addict & Mental Hlth, PET Ctr, Toronto, ON M5T 1R8, Canada. [Cao, Pengpeng; van Oosten, Erik M.] Univ Toronto, Dept Chem, Toronto, ON M5S 1A1, Canada. [Hao, Guiyang; Sun, Xiankai; Slavine, Nikolai; Alhasan, Mustafa; Antich, Peter P.; Bonte, Frederick J.; Kulkarni, Padmakar] Univ Texas SW Med Ctr Dallas, Dept Radiol, Dallas, TX 75390 USA. RP Vasdev, N (reprint author), Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging Radiol, 55 Fruit St White 427, Boston, MA 02114 USA. EM vasdev.neil@mgh.harvard.edu RI Wilson, Alan/A-1788-2011 FU Worsham Fund; NIH (NIA) [1RCA1AG03308] FX The authors thank Dr Alan Lough for his expertise with X-ray crystallography and Dr Bao-Xi Qu for providing the transgenic animals. We also thank Dr Karin Stephenson, Dr Matthew Moran, Veera Arora, Srinivas Chiguru and Michael Long for helpful discussions and/or technical assistance. This study was conducted with the support of the Worsham Fund and the NIH (NIA; Grant # 1RCA1AG03308). NR 29 TC 16 Z9 16 U1 1 U2 10 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-2503 J9 MEDCHEMCOMM JI MedChemComm PD OCT PY 2012 VL 3 IS 10 BP 1228 EP 1230 DI 10.1039/c2md20075a PG 3 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 028LK UT WOS:000310423600003 ER PT J AU Peifer, M Fernandez-Cuesta, L Sos, ML George, J Seidel, D Kasper, LH Plenker, D Leenders, F Sun, RP Zander, T Menon, R Koker, M Dahmen, I Muller, C Di Cerbo, V Schildhaus, HU Altmuller, J Baessmann, I Becker, C de Wilde, B Vandesompele, J Bohm, D Ansen, S Gabler, F Wilkening, I Heynck, S Heuckmann, JM Lu, X Carter, SL Cibulskis, K Banerji, S Getz, G Park, KS Rauh, D Grutter, C Fischer, M Pasqualucci, L Wright, G Wainer, Z Russell, P Petersen, I Chen, Y Stoelben, E Ludwig, C Schnabel, P Hoffmann, H Muley, T Brockmann, M Engel-Riedel, W Muscarella, LA Fazio, VM Groen, H Timens, W Sietsma, H Thunnissen, E Smit, E Heideman, DAM Snijders, PJF Cappuzzo, F Ligorio, C Damiani, S Field, J Solberg, S Brustugun, OT Lund-Iversen, M Sanger, J Clement, JH Soltermann, A Moch, H Weder, W Solomon, B Soria, JC Validire, P Besse, B Brambilla, E Brambilla, C Lantuejoul, S Lorimier, P Schneider, PM Hallek, M Pao, W Meyerson, M Sage, J Shendure, J Schneider, R Buttner, R Wolf, J Nurnberg, P Perner, S Heukamp, LC Brindle, PK Haas, S Thomas, RK AF Peifer, Martin Fernandez-Cuesta, Lynnette Sos, Martin L. George, Julie Seidel, Danila Kasper, Lawryn H. Plenker, Dennis Leenders, Frauke Sun, Ruping Zander, Thomas Menon, Roopika Koker, Mirjam Dahmen, Ilona Mueller, Christian Di Cerbo, Vincenzo Schildhaus, Hans-Ulrich Altmueller, Janine Baessmann, Ingelore Becker, Christian de Wilde, Bram Vandesompele, Jo Boehm, Diana Ansen, Sascha Gabler, Franziska Wilkening, Ines Heynck, Stefanie Heuckmann, Johannes M. Lu, Xin Carter, Scott L. Cibulskis, Kristian Banerji, Shantanu Getz, Gad Park, Kwon-Sik Rauh, Daniel Gruetter, Christian Fischer, Matthias Pasqualucci, Laura Wright, Gavin Wainer, Zoe Russell, Prudence Petersen, Iver Chen, Yuan Stoelben, Erich Ludwig, Corinna Schnabel, Philipp Hoffmann, Hans Muley, Thomas Brockmann, Michael Engel-Riedel, Walburga Muscarella, Lucia A. Fazio, Vito M. Groen, Harry Timens, Wim Sietsma, Hannie Thunnissen, Erik Smit, Egbert Heideman, Danielle A. M. Snijders, Peter J. F. Cappuzzo, Federico Ligorio, Claudia Damiani, Stefania Field, John Solberg, Steinar Brustugun, Odd Terje Lund-Iversen, Marius Saenger, Joerg Clement, Joachim H. Soltermann, Alex Moch, Holger Weder, Walter Solomon, Benjamin Soria, Jean-Charles Validire, Pierre Besse, Benjamin Brambilla, Elisabeth Brambilla, Christian Lantuejoul, Sylvie Lorimier, Philippe Schneider, Peter M. Hallek, Michael Pao, William Meyerson, Matthew Sage, Julien Shendure, Jay Schneider, Robert Buettner, Reinhard Wolf, Juergen Nuernberg, Peter Perner, Sven Heukamp, Lukas C. Brindle, Paul K. Haas, Stefan Thomas, Roman K. TI Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer SO NATURE GENETICS LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; MOUSE MODEL; NEUROENDOCRINE TUMORS; FREQUENT MUTATION; PROSTATE-CANCER; EGFR MUTATIONS; P53 REGULATION; EPH-RECEPTOR; E-CADHERIN; GENE AB Small-cell lung cancer (SCLC) is an aggressive lung tumor subtype with poor prognosis(1-3). We sequenced 29 SCLC exomes, 2 genomes and 15 transcriptomes and found an extremely high mutation rate of 7.4 +/- 1 protein-changing mutations per million base pairs. Therefore, we conducted integrated analyses of the various data sets to identify pathogenetically relevant mutated genes. In all cases, we found evidence for inactivation of TP53 and RB1 and identified recurrent mutations in the CREBBP, EP300 and MLL genes that encode histone modifiers. Furthermore, we observed mutations in PTEN, SLIT2 and EPHA7, as well as focal amplifications of the FGFR1 tyrosine kinase gene. Finally, we detected many of the alterations found in humans in SCLC tumors from Tp53 and Rb1 double knockout mice(4). Our study implicates histone modification as a major feature of SCLC, reveals potentially therapeutically tractable genomic alterations and provides a generalizable framework for the identification of biologically relevant genes in the context of high mutational background. C1 [Peifer, Martin; Fernandez-Cuesta, Lynnette; Sos, Martin L.; George, Julie; Seidel, Danila; Plenker, Dennis; Leenders, Frauke; Zander, Thomas; Koker, Mirjam; Dahmen, Ilona; Mueller, Christian; Heuckmann, Johannes M.; Lu, Xin; Thomas, Roman K.] Univ Cologne, Dept Translat Genom, D-50931 Cologne, Germany. [Peifer, Martin; Fernandez-Cuesta, Lynnette; Sos, Martin L.; George, Julie; Seidel, Danila; Plenker, Dennis; Leenders, Frauke; Zander, Thomas; Koker, Mirjam; Dahmen, Ilona; Mueller, Christian; Gabler, Franziska; Wilkening, Ines; Heynck, Stefanie; Heuckmann, Johannes M.; Lu, Xin; Thomas, Roman K.] Univ Cologne, Max Planck Inst Neurol Res, Klaus Joachim Zulch Labs, Max Planck Soc, D-50931 Cologne, Germany. [Peifer, Martin; Fernandez-Cuesta, Lynnette; Sos, Martin L.; George, Julie; Seidel, Danila; Plenker, Dennis; Leenders, Frauke; Zander, Thomas; Koker, Mirjam; Dahmen, Ilona; Mueller, Christian; Gabler, Franziska; Wilkening, Ines; Heynck, Stefanie; Heuckmann, Johannes M.; Lu, Xin; Thomas, Roman K.] Univ Cologne, Fac Med, D-50931 Cologne, Germany. [Sos, Martin L.; Zander, Thomas; Ansen, Sascha; Hallek, Michael; Wolf, Juergen; Thomas, Roman K.] Univ Cologne, Dept Internal Med 1, D-50931 Cologne, Germany. [Sos, Martin L.; Zander, Thomas; Ansen, Sascha; Hallek, Michael; Wolf, Juergen; Thomas, Roman K.] Univ Cologne, Ctr Integrated Oncol Koln Bonn, D-50931 Cologne, Germany. [Seidel, Danila; Leenders, Frauke; Hallek, Michael; Buettner, Reinhard; Wolf, Juergen; Thomas, Roman K.] Univ Cologne, Lab Translat Canc Genom, Ctr Integrated Oncol Kolm Bonn, D-50931 Cologne, Germany. [Kasper, Lawryn H.; Brindle, Paul K.] St Jude Childrens Res Hosp, Dept Biochem, Memphis, TN 38105 USA. [Sun, Ruping; Haas, Stefan] Max Planck Inst Mol Genet, D-14195 Berlin, Germany. [Menon, Roopika; Boehm, Diana; Perner, Sven] Univ Hosp Bonn, Inst Prostate Canc Res, Inst Pathol, Bonn, Germany. [Di Cerbo, Vincenzo; Schneider, Robert] Max Planck Inst Immunobiol & Epigenet, Freiburg, Germany. [Schildhaus, Hans-Ulrich; Buettner, Reinhard; Heukamp, Lukas C.; Thomas, Roman K.] Univ Cologne, Dept Pathol, Cologne, Germany. [Altmueller, Janine; Baessmann, Ingelore; Becker, Christian; Nuernberg, Peter] Univ Cologne, Cologne Ctr Genom, D-50931 Cologne, Germany. [de Wilde, Bram; Vandesompele, Jo] Univ Ghent, Ctr Med Genet, B-9000 Ghent, Belgium. [Carter, Scott L.; Cibulskis, Kristian; Banerji, Shantanu; Getz, Gad; Meyerson, Matthew] Broad Inst Harvard & MIT, Cambridge, MA USA. [Park, Kwon-Sik; Sage, Julien] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. [Park, Kwon-Sik; Sage, Julien] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Rauh, Daniel; Gruetter, Christian] Tech Univ Dortmund, Dept Chem Biol, Dortmund, Germany. [Fischer, Matthias] Univ Childrens Hosp Cologne, Dept Pediat Oncol & Hematol, Cologne, Germany. [Fischer, Matthias; Nuernberg, Peter] Univ Cologne, CMMC, D-50931 Cologne, Germany. [Pasqualucci, Laura] Columbia Univ, Inst Canc Genet, New York, NY USA. [Pasqualucci, Laura] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY USA. [Wright, Gavin; Wainer, Zoe] Univ Melbourne, Dept Surg, St Vincents Hosp, Melbourne, Vic, Australia. [Russell, Prudence] St Vincents Hosp, Dept Pathol, Melbourne, Vic, Australia. [Petersen, Iver; Chen, Yuan] Univ Jena, Jena Univ Hosp, Inst Pathol, Jena, Germany. [Stoelben, Erich; Ludwig, Corinna; Engel-Riedel, Walburga] Kliniken Stadt Koln, Lungenklin Merheim, Dept Thorac Surg, Cologne, Germany. [Schnabel, Philipp] Univ Heidelberg, Inst Pathol, D-6900 Heidelberg, Germany. [Hoffmann, Hans; Muley, Thomas] Thoraxklin Heidelberg, Dept Thorac Surg, Heidelberg, Germany. [Brockmann, Michael] Hosp Merheim, Dept Pathol, Kliniken Stadt Koln, Cologne, Germany. [Muscarella, Lucia A.; Fazio, Vito M.] Ist Ricovero & Cura Carattere Sci IRCCS Casa Soll, Lab Oncol, San Giovanni Rotondo, Italy. [Groen, Harry] Univ Groningen, Univ Med Ctr Groningen, Dept Pulm Dis, NL-9713 AV Groningen, Netherlands. [Timens, Wim; Sietsma, Hannie] Univ Med Ctr Groningen, Dept Pathol, NL-9713 AV Groningen, Netherlands. [Thunnissen, Erik; Heideman, Danielle A. M.; Snijders, Peter J. F.] Vrije Univ Amsterdam, Med Ctr, Dept Pathol, Amsterdam, Netherlands. [Smit, Egbert] Vrije Univ Amsterdam, Med Ctr, Dept Pulm Dis, Amsterdam, Netherlands. [Cappuzzo, Federico] Osped Civile, Dept Med Oncol, Livorno, Italy. [Ligorio, Claudia; Damiani, Stefania] Univ Hosp Bologna, Dept Haematol & Oncol Sci, Bologna, Italy. [Field, John] Univ Liverpool, Roy Castle Lung Canc Res Programme, Canc Res Ctr, Liverpool L69 3BX, Merseyside, England. [Solberg, Steinar] Oslo Univ Hosp, Rikshosp, Dept Thorac Surg, Oslo, Norway. [Brustugun, Odd Terje] Univ Oslo, Fac Med, Inst Clin Med, Oslo, Norway. [Brustugun, Odd Terje] Oslo Univ Hosp, Norwegian Radium Hosp, Dept Oncol, Oslo, Norway. [Lund-Iversen, Marius] Oslo Univ Hosp, Norwegian Radium Hosp, Dept Pathol, Oslo, Norway. [Saenger, Joerg] Inst Pathol Bad Berka, Bad Berka, Germany. [Clement, Joachim H.] Univ Jena, Dept Internal Med 2, Jena Univ Hosp, Jena, Germany. [Soltermann, Alex; Moch, Holger] Univ Zurich Hosp, Inst Surg Pathol, CH-8091 Zurich, Switzerland. [Weder, Walter] Univ Zurich Hosp, Div Thorac Surg, CH-8091 Zurich, Switzerland. [Solomon, Benjamin] Peter MacCallum Canc Ctr, Dept Haematol & Med Oncol, Melbourne, Vic, Australia. [Soria, Jean-Charles; Besse, Benjamin] Inst Gustave Roussy, Dept Med, Phase Unit 1, Villejuif, France. [Validire, Pierre] Inst Mutualiste Montsouris, France Serv Anat Pathol, Paris, France. [Brambilla, Elisabeth; Brambilla, Christian; Lantuejoul, Sylvie; Lorimier, Philippe] Univ Grenoble 1, Dept Pathol, Grenoble, France. [Brambilla, Elisabeth; Brambilla, Christian; Lantuejoul, Sylvie] Univ Grenoble 1, Inst Albert Bonniot, INSERM U823, Grenoble, France. [Schneider, Peter M.] Univ Cologne, Inst Legal Med, D-50931 Cologne, Germany. [Pao, William] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Meyerson, Matthew] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Shendure, Jay] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Schneider, Robert] Univ Strasbourg, CNRS UMR 7104, INSERM U964, Inst Genet & Biol Mol & Cellulaire, Illkirch Graffenstaden, France. [Nuernberg, Peter] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50931 Cologne, Germany. RP Thomas, RK (reprint author), Univ Cologne, Dept Translat Genom, D-50931 Cologne, Germany. EM roman.thomas@uni-koeln.de RI Rauh, Daniel/G-1595-2013; Schildhaus, Hans-Ulrich/J-3094-2012; BRAMBILLA, CHRISTIAN/K-2285-2013; Timens, Wim/K-5570-2013; Heukamp, Lukas/A-8338-2013; Brambilla, Elisabeth/L-8796-2013; Lantuejoul, Sylvie/N-4671-2013; Fazio, Vito Michele/H-3007-2016; Muscarella, Lucia Anna/K-5979-2016 OI Cappuzzo, Federico/0000-0002-6295-6767; Field, John/0000-0003-3951-6365; Wright, Gavin/0000-0002-7000-9305; Rauh, Daniel/0000-0002-1970-7642; Shendure, Jay/0000-0002-1516-1865; Di Cerbo, Vincenzo/0000-0002-2920-1274; Vandesompele, Jo/0000-0001-6274-0184; DAMIANI, STEFANIA/0000-0002-2757-5985; Seidel, Danila/0000-0003-4388-3117; Thunnissen, Erik/0000-0001-5355-8508; Timens, Wim/0000-0002-4146-6363; Fazio, Vito Michele/0000-0002-7751-1867; Muscarella, Lucia Anna/0000-0002-1866-8151 FU German Ministry of Science and Education (BMBF) as part of the NGFNplus program [01GS08100, 01GS08101]; Max Planck Society [M.I..F.A.NEUR8061]; Deutsche Forschungsgemeinschaft (DFG) [SFB832, TP6, TP5, Z1, TH1386/3-1]; European Union's Framework Programme CURELUNG [HEALTH-F2-2010-258677]; Stand Up To Cancer-American Association for Cancer Research Innovative Research Grant [SU2C-AACR-IR60109]; Behrens-Weise Foundation; US National Institutes of Health (NIH) Cancer Center [P30 CA021765]; American Lebanese Syrian Associated Charities of St. Jude Children's Research Hospital; Associazione Italiana Ricerca sul Cancro (AIRC) [IG 9425] FX We are indebted to the individuals donating their tumor specimens as part of the Clinical Lung Cancer Genome Project initiative. Additional biospecimens for this study were obtained from the Victorian Cancer Biobank (Melbourne, Australia). The Institutional Review Board (IRB) of each participating institution approved collection and use of all specimens in this study. We also thank our colleagues at The Cancer Genome Atlas Research Network (TCGA) and A.L. Kung for invaluable discussion and many helpful comments. This work was supported by the German Ministry of Science and Education (BMBF) as part of the NGFNplus program (grant 01GS08100 to R.K.T. and 01GS08101 to J.W. and P.N.), by the Max Planck Society (M.I..F.A.NEUR8061 to R.K.T.), by the Deutsche Forschungsgemeinschaft (DFG) through SFB832 (TP6 to R.K.T. and TP5 and Z1 to L.C.H. and R.B.) and TH1386/3-1 (to R.K.T. and M.L.S.), by the European Union's Framework Programme CURELUNG (HEALTH-F2-2010-258677 to R.K.T., J.F., E.B., C. Brambilla, S.L., B.B. and J.W.), by Stand Up To Cancer-American Association for Cancer Research Innovative Research Grant (SU2C-AACR-IR60109 to R.K.T. and W.P.), by the Behrens-Weise Foundation (to R.K.T.) and by an anonymous foundation to R.K.T. M.L.S. is a fellow of the International Association for the Study of Lung Cancer (IASLC). P.K.B. and L.H.K. thank the St. Jude Cell and Tissue Imaging facility and acknowledge support from the US National Institutes of Health (NIH) Cancer Center (grant P30 CA021765) and the American Lebanese Syrian Associated Charities of St. Jude Children's Research Hospital. F.C. was supported by Associazione Italiana Ricerca sul Cancro (AIRC, grant IG 9425). NR 90 TC 354 Z9 363 U1 9 U2 87 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 2012 VL 44 IS 10 BP 1104 EP + DI 10.1038/ng.2396 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 016WJ UT WOS:000309550200009 PM 22941188 ER PT J AU Holliday, EG Maguire, JM Evans, TJ Koblar, SA Jannes, J Sturm, JW Hankey, GJ Baker, R Golledge, J Parsons, MW Malik, R McEvoy, M Biros, E Lewis, MD Lincz, LF Peel, R Oldmeadow, C Smith, W Moscato, P Barlera, S Bevan, S Bis, JC Boerwinkle, E Boncoraglio, GB Brott, TG Brown, RD Cheng, YC Cole, JW Cotlarciuc, I Devan, WJ Fornage, M Furie, KL Gretarsdottir, S Gschwendtner, A Ikram, MA Longstreth, WT Meschia, JF Mitchell, BD Mosley, TH Nalls, MA Parati, EA Psaty, BM Sharma, P Stefansson, K Thorleifsson, G Thorsteinsdottir, U Traylor, M Verhaaren, BFJ Wiggins, KL Worrall, BB Sudlow, C Rothwell, PM Farrall, M Dichgans, M Rosand, J Markus, HS Scott, RJ Levi, C Attia, J AF Holliday, Elizabeth G. Maguire, Jane M. Evans, Tiffany-Jane Koblar, Simon A. Jannes, Jim Sturm, Jonathan W. Hankey, Graeme J. Baker, Ross Golledge, Jonathan Parsons, Mark W. Malik, Rainer McEvoy, Mark Biros, Erik Lewis, Martin D. Lincz, Lisa F. Peel, Roseanne Oldmeadow, Christopher Smith, Wayne Moscato, Pablo Barlera, Simona Bevan, Steve Bis, Joshua C. Boerwinkle, Eric Boncoraglio, Giorgio B. Brott, Thomas G. Brown, Robert D., Jr. Cheng, Yu-Ching Cole, John W. Cotlarciuc, Ioana Devan, William J. Fornage, Myriam Furie, Karen L. Gretarsdottir, Solveig Gschwendtner, Andreas Ikram, M. Arfan Longstreth, W. T., Jr. Meschia, James F. Mitchell, Braxton D. Mosley, Thomas H. Nalls, Michael A. Parati, Eugenio A. Psaty, Bruce M. Sharma, Pankaj Stefansson, Kari Thorleifsson, Gudmar Thorsteinsdottir, Unnur Traylor, Matthew Verhaaren, Benjamin F. J. Wiggins, Kerri L. Worrall, Bradford B. Sudlow, Cathie Rothwell, Peter M. Farrall, Martin Dichgans, Martin Rosand, Jonathan Markus, Hugh S. Scott, Rodney J. Levi, Christopher Attia, John CA Australian Stroke Genetics Collabo International Stroke Genetics Cons Wellcome Trust Case Control Consor TI Common variants at 6p21.1 are associated with large artery atherosclerotic stroke SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; L GENE-CLUSTER; ISCHEMIC-STROKE; ATRIAL-FIBRILLATION; GENOTYPE DATA; HERITABILITY; METAANALYSIS; RISK; CLASSIFICATION; VISUALIZATION AB Genome-wide association studies (GWAS) have not consistently detected replicable genetic risk factors for ischemic stroke, potentially due to etiological heterogeneity of this trait. We performed GWAS of ischemic stroke and a major ischemic stroke subtype (large artery atherosclerosis, LAA) using 1,162 ischemic stroke cases (including 421 LAA cases) and 1,244 population controls from Australia. Evidence for a genetic influence on ischemic stroke risk was detected, but this influence was higher and more significant for the LAA subtype. We identified a new LAA susceptibility locus on chromosome 6p21.1 (rs556621: odds ratio (OR) = 1.62, P = 3.9 x 10(-8)) and replicated this association in 1,715 LAA cases and 52,695 population controls from 10 independent population cohorts (meta-analysis replication OR = 1.15, P = 3.9 x 10(-4); discovery and replication combined OR = 1.21, P = 4.7 x 10(-8)). This study identifies a genetic risk locus for LAA and shows how analyzing etiological subtypes may better identify genetic risk alleles for ischemic stroke. C1 [Holliday, Elizabeth G.; McEvoy, Mark; Peel, Roseanne; Attia, John] Univ Newcastle, Sch Med & Publ Hlth, Ctr Clin Epidemiol & Biostat, Newcastle, NSW 2300, Australia. [Holliday, Elizabeth G.; Evans, Tiffany-Jane; Moscato, Pablo; Scott, Rodney J.; Attia, John] Hunter Med Res Inst, Ctr Bioinformat Biomarker Discovery & Informat Ba, Newcastle, NSW, Australia. [Maguire, Jane M.] Univ Newcastle, Sch Nursing & Midwifery, Newcastle, NSW 2300, Australia. [Maguire, Jane M.; Parsons, Mark W.; Lincz, Lisa F.; Levi, Christopher] Univ Newcastle, Ctr Brain & Mental Hlth Res, Newcastle, NSW 2300, Australia. [Maguire, Jane M.; Sturm, Jonathan W.] Gosford Hosp, Cent Coast Area Hlth, Dept Neurosci, Gosford, NSW, Australia. [Evans, Tiffany-Jane; Lincz, Lisa F.; Scott, Rodney J.] Univ Newcastle, Sch Biomed Sci & Pharm, Newcastle, NSW 2300, Australia. [Koblar, Simon A.; Jannes, Jim; Lewis, Martin D.] Univ Adelaide, Sch Med, Stroke Res Program, Adelaide, SA, Australia. [Koblar, Simon A.; Jannes, Jim] Queen Elizabeth Hosp, Dept Neurol, Stroke Unit, Adelaide, SA, Australia. [Hankey, Graeme J.] Royal Perth Hosp, Dept Neurol, Perth, WA, Australia. [Hankey, Graeme J.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia. [Baker, Ross] Royal Perth Hosp, Dept Haematol, Perth, WA, Australia. [Baker, Ross] Murdoch Univ, Ctr Thrombosis & Haemophilia, Perth, WA, Australia. [Golledge, Jonathan; Biros, Erik] James Cook Univ, Sch Med & Dent, Vasc Biol Unit, Townsville, Qld, Australia. [Golledge, Jonathan] Townsville Hosp, Dept Vasc Surg, Townsville, Qld, Australia. [Malik, Rainer; Gschwendtner, Andreas; Dichgans, Martin] Univ Munich, Inst Stroke & Dementia Res ISD, Med Ctr, Klinikum Univ Munchen, Munich, Germany. [McEvoy, Mark; Peel, Roseanne; Smith, Wayne] Hunter Med Res Inst, Publ Hlth Res Program, Newcastle, NSW, Australia. [Lewis, Martin D.] Univ Adelaide, Discipline Genet, Sch Mol & Biomed Sci, Adelaide, SA, Australia. [Lincz, Lisa F.] Calvary Mater Newcastle Hosp, Hunter Haematol Res Grp, Newcastle, NSW, Australia. [Oldmeadow, Christopher] Hunter Med Res Inst, Clin Res Design IT & Stat Support Unit, Newcastle, NSW, Australia. [Moscato, Pablo] Univ Newcastle, Sch Elect Engn & Comp Sci, Newcastle, NSW 2300, Australia. [Barlera, Simona] Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy. [Bevan, Steve; Traylor, Matthew; Markus, Hugh S.] St Georges Univ London, Stroke & Dementia Res Ctr, London, England. [Bis, Joshua C.; Psaty, Bruce M.; Wiggins, Kerri L.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Boerwinkle, Eric; Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX USA. [Boerwinkle, Eric; Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX USA. [Boncoraglio, Giorgio B.; Parati, Eugenio A.] Ist Neurol Carlo Besta, Dept Cerebrovasc Dis, Fdn Ist Ricovero & Cura Carattere Sci IRCCS, Milan, Italy. [Brott, Thomas G.; Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. [Brown, Robert D., Jr.] Mayo Clin, Dept Neurol, Rochester, MN USA. [Cheng, Yu-Ching; Mitchell, Braxton D.] Univ Maryland, Dept Med, Baltimore, MD 21201 USA. [Cole, John W.] Baltimore Vet Affairs Med Ctr, Baltimore, MD USA. [Cole, John W.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Cotlarciuc, Ioana; Sharma, Pankaj] Univ London Imperial Coll Sci Technol & Med, ICCRU, London, England. [Devan, William J.; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Devan, William J.; Furie, Karen L.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Devan, William J.; Furie, Karen L.; Rosand, Jonathan] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Gretarsdottir, Solveig; Stefansson, Kari; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur] deCODE Genet, Reykjavik, Iceland. [Ikram, M. Arfan; Verhaaren, Benjamin F. J.] Univ Med Ctr, Erasmus Med Ctr MC, Dept Epidemiol, Rotterdam, Netherlands. [Ikram, M. Arfan] Erasmus MC Univ Med Ctr, Dept Neurol, Rotterdam, Netherlands. [Ikram, M. Arfan; Verhaaren, Benjamin F. J.] Erasmus MC Univ Med Ctr, Dept Radiol, Rotterdam, Netherlands. [Longstreth, W. T., Jr.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Longstreth, W. T., Jr.] Univ Washington, Dept Med, Seattle, WA USA. [Longstreth, W. T., Jr.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Mosley, Thomas H.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. [Nalls, Michael A.] NIA, Lab Neurogenet, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth, Seattle, WA USA. [Stefansson, Kari; Thorsteinsdottir, Unnur] Univ Iceland, Fac Med, Reykjavik, Iceland. [Worrall, Bradford B.] Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Sudlow, Cathie] Univ Edinburgh, Div Clin Neurosci, Edinburgh, Midlothian, Scotland. [Sudlow, Cathie] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland. [Rothwell, Peter M.] John Radcliffe Hosp, Dept Clin Neurol, Oxford OX3 9DU, England. [Farrall, Martin] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Farrall, Martin] Univ Oxford, Dept Cardiovasc Med, Oxford, England. [Scott, Rodney J.] Hunter Area Pathol Serv, Div Genet, Newcastle, NSW, Australia. RP Holliday, EG (reprint author), Univ Newcastle, Sch Med & Publ Hlth, Ctr Clin Epidemiol & Biostat, Newcastle, NSW 2300, Australia. EM liz.holliday@newcastle.edu.au RI Scott, Rodney/B-2827-2013; MOSCATO, PABLO/G-7668-2013; Peel, Roseanne/G-7726-2013; golledge, jonathan/I-2371-2013; Attia, John/F-5376-2013; EVANS, TIFFANY-JANE/G-8001-2013; Parsons, Mark/G-3750-2014; Hankey, Graeme /H-4968-2014; Boncoraglio, Giorgio/B-8647-2011; OI Lewis, Martin/0000-0002-3332-3776; Koblar, Simon/0000-0002-8667-203X; Mitchell, Braxton/0000-0003-4920-4744; Scott, Rodney/0000-0001-7724-3404; Traylor, Matthew/0000-0001-6624-8621; Bevan, Steve/0000-0003-0490-6830; Peel, Roseanne/0000-0001-9912-3198; Attia, John/0000-0001-9800-1308; EVANS, TIFFANY-JANE/0000-0001-7525-461X; Hankey, Graeme /0000-0002-6044-7328; Ikram, Mohammad Arfan/0000-0003-0372-8585 FU University of Newcastle; Australian National Health and Medical Research Council (NHMRC) [569257]; Australian National Heart Foundation (NHF) [G 04S 1623]; Gladys M Brawn Fellowship scheme; Vincent Fairfax Family Foundation in Australia; Australian Office of Health and Medical Research; Wellcome Trust [085475/B/08/Z, 085475/Z/08/Z, WT084724MA, 090532/Z/09/Z]; European Community [LSHM-CT-2007037273]; AstraZeneca; US National Institute of Neurological Disorders and Stroke [U01NS069208]; Netherlands Heart Foundation [2009B102] FX A complete list of funding acknowledgments is included in the Supplementary Note. We are grateful to the participants with ischemic stroke and also to their families for participating in this study. Australian population control data were derived from the Hunter Community Study. We also thank the University of Newcastle for funding and the men and women of the Hunter region who participated in this study. This research was funded by grants from the Australian National Health and Medical Research Council (NHMRC; project grant 569257), the Australian National Heart Foundation (NHF; project grant G 04S 1623), the University of Newcastle, the Gladys M Brawn Fellowship scheme and the Vincent Fairfax Family Foundation in Australia. E.G.H. is supported by the Australian NHMRC Fellowship scheme. J.G. is supported by a Practitioner Fellowship from the NHMRC and a Senior Clinical Research Fellowship from the Australian Office of Health and Medical Research. The principal funding for the Wellcome Trust Case Control Consortium 2 (WTCCC2) ischemic stroke study was provided by the Wellcome Trust, as part of the WTCCC2 project (085475/B/08/Z, 085475/Z/08/Z and WT084724MA). This work was also supported by the European Community's Sixth Framework Programme (LSHM-CT-2007037273), the Wellcome Trust core award (090532/Z/09/Z) and AstraZeneca. M. Farrall is a member of the Oxford British Heart Foundation (BHF) Centre of Research Excellence. The Siblings with Ischemic Stroke Study (SWISS) and the Ischemic Stroke Genetics Study (ISGS) were funded by grants from the US National Institute of Neurological Disorders and Stroke. Additional funding was provided by the US National Institute of Neurological Disorders and Stroke (U01NS069208). The Rotterdam Study received principal funding for this report from the Netherlands Heart Foundation (grant 2009B102). NR 37 TC 75 Z9 77 U1 1 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD OCT PY 2012 VL 44 IS 10 BP 1147 EP + DI 10.1038/ng.2397 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 016WJ UT WOS:000309550200017 PM 22941190 ER PT J AU Gonzalez-Heydrich, J Hamoda, HM Luna, L Rao, S McClendon, J Rotella, P Waber, D Boyer, K Faraone, SV Whitney, J Guild, D Biederman, J AF Gonzalez-Heydrich, Joseph Hamoda, Hesham M. Luna, Laura Rao, Sneha McClendon, James Rotella, Peter Waber, Deborah Boyer, Katherine Faraone, Steven V. Whitney, Jane Guild, Danielle Biederman, Joseph TI Elevated rates of ADHD in mothers of children with comorbid ADHD and epilepsy SO NEUROPSYCHIATRY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT-HYPERACTIVITY DISORDER; PSYCHOPATHOLOGY; ADOLESCENTS; SYMPTOMS; DEPRESSION; CHILDHOOD; FAMILIES; ADULTS AB Objectives: To describe the prevalence of ADHD in mothers of children with comorbid ADHD and epilepsy (ADHD+E) and to compare ADHD symptoms in mothers with (Fam(+)) and without (Fam(-)) additional relative(s) with epilepsy. Patients & methods: Mothers (n = 16) of children with ADHD+E were assessed by the Kiddie Schedule for Affective Disorders and Schizophrenia for School Age Children ADHD module and the ADHD Rating Scale IV. Information was collected on the presence (Fam(+)) or absence (Fam(-)) of first- or second-degree relatives with epilepsy in the sample. Results: A total of 50% of mothers met the DSM-IV criteria for ADHD. ADHD was more prevalent in Fam(+) mothers (80%) compared with Fam- mothers (36%; p = 0.14). Fam(+) mothers had more current hyperactivity symptoms than Fam- mothers (p = 0.002), higher current ADHD severity (p = 0.02) and higher ADHD Rating Scale IV hyperactivity scores (p = 0.008). Conclusion: The prevalence of ADHD in mothers of children with ADHD+E is elevated in this pilot study, suggesting that ADHD symptoms in children with epilepsy and their mothers reflects shared familial genetic or environmental risks, potentially resulting in a higher prevalence of both disorders among family members. This is a pilot study and larger controlled studies are warranted. C1 [Gonzalez-Heydrich, Joseph; Hamoda, Hesham M.; Luna, Laura; Rao, Sneha; McClendon, James; Rotella, Peter; Waber, Deborah; Boyer, Katherine; Whitney, Jane; Guild, Danielle] Harvard Univ, Sch Med, Dept Psychiat, Boston Childrens Hosp, Boston, MA 02115 USA. [Faraone, Steven V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. [Biederman, Joseph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Res Unit, Boston, MA USA. RP Gonzalez-Heydrich, J (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Boston Childrens Hosp, Boston, MA 02115 USA. EM joseph.gonzalez-heydrich@childrens.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH K23 [MH066835-04]; Dupont-Warren Fellowship; Livingston Fellowship; Harvard Medical School Fellowship, Eleanor and Miles Shore Fellowship Program; Elminda; Janssen; McNeil; Shire; The Children's Hospital of Southwest Florida/Lee Memorial Health System; single talk given at Fundacion Dr Manuel Camel AC in Monterrey Mexico; MGH Psychiatry Academy; Abbott; Alza; AstraZeneca; Boston University; Bristol Myers Squibb; Celltech; Cephalon; Eli Lilly and Co.; Esai; Fundacion Areces (Spain); Forest; GlaxoSmithKline; Gliatech; Hastings Center; Medice Pharmaceuticals (Germany); Neurosearch; Organon; Otsuka; Pfizer; Merck; MMC; MMC Pediatric; NARSAD; NIDA; New River; NICHD; NIMH; Novartis; Noven; Pharmacia; Phase V Communications; Physicians Academy; The Prechter Foundation; Quantia Communications; Reed Exhibitions; Spanish Child Psychiatry Association; The Stanley Foundation; UCB Pharma Inc.; Veritas; Wyeth; Alcobra; NIH; Tommy Fuss Fund; Al Rashed Family; Pfizer Inc.; Johnson Johnson; Abbott Laboratories; Akzo-Nobel/Organon FX This research was supported by NIMH K23 grant MH066835-04. HM Hamoda was supported by the Dupont-Warren and Livingston Fellowships, as well as a Harvard Medical School Fellowship as part of the Eleanor and Miles Shore Fellowship Program. J Biederman is currently receiving research support from the following sources: Elminda, Janssen, McNeil and Shire. In 2012, J Biederman received an honorarium from the MGH Psychiany Academy and The Children's Hospital of Southwest Florida/Lee Memorial Health System for tuition-funded CME courses. In 2011, J Biederman gave a single unpaid talk for Juste Pharmaceutical Spain, received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course, and received honoraria for presenting at international scientific conference on ADHD. He also received an honorarium from Cambridge University Press for a chapter publication. J Biederman received departmental royalties from a copyrighted rating scale used for ADHD diagnoses, paid by Eli Lilly and Co., Shire and AstraZeneca; these royalties are paid to the Department of Psychiatry at MGH. In 2010, J Biederman received a speaker's fee from a single talk given at Fundacion Dr Manuel Camel AC in Monterrey Mexico. I Biederman provided single consultations for Shionogi Pharma Inc. and Cipher Pharmaceuticals Inc.; the honoraria for these consultations were paid to the Department of Psychiatry at the MGH. J Biederman received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course. In previous years, J Biederman received research support, consultation fees or speaker's fees for/from the following additional sources: Abbott, Alza, AstraZeneca, Boston University, Bristol Myers Squibb, Celltech, Cephalon, Eli Lilly and Co., Esai, Fundacion Areces (Spain), Forest, GlaxoSmithKline, Gliatech, Hastings Center, Janssen, McNeil, Medice Pharmaceuticals (Germany), Merck, MMC Pediatric, NARSAD, NIDA, New River, NICHD, NIMH, Novartis, Noven, Neurosearch, Organon, Otsuka, Pfizer, Pharmacia, Phase V Communications, Physicians Academy, The Prechter Foundation, Quantia Communications, Reed Exhibitions, Shire, the Spanish Child Psychiatry Association, The Stanley Foundation, UCB Pharma Inc., Veritas and Wyeth. In the past year, SV Faraone received consulting income and/or research support from Shire, Otsuka and Alcobra and research support from the NIH. He is also on the Clinical Advisory Board for Akili Interactive Labs. In previous years, he received consulting fees, was on Advisory Boards or participated in CME programs sponsored by Shire, McNeil, Janssen, Novartis, Pfizer and Eli Lilly and Co. SV Faraone receives royalties from books published by Guilford Press: Straight Talk about Your Child's Mental Health and Oxford University Press: Schizophrenia: The Facts. In the past year, J Gonzalez-Heydrich, has received grant support from the Tommy Fuss Fund, the Al Rashed Family, Pfizer Inc., GlaxoSmithKline and Johnson & Johnson. In previous years, he has served as a consultant to Abbott Laboratories, Pfizer Inc, Johnson dr Johnson (Janssen, McNeil Consumer Health), Novartis, Parke-Davis, GlaxoSmithKline, AstraZeneca and Seaside Therapeutics; has been a speaker for Abbott Laboratories, Pfizer Inc, Novartis, Bristol-Meyers Squibb; and has received grant support from Abbott Laboratories, Pfizer Inc, Johnson & Johnson (Janssen, McNeil Consumer Health), Akzo-Nobel/Organon and the NIMH.; 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. No writing assistance was utilized in the production of this manuscript. NR 30 TC 2 Z9 2 U1 1 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1758-2008 J9 NEUROPSYCHIATRY-LOND JI Neuropsychiatry PD OCT PY 2012 VL 2 IS 5 BP 385 EP 391 DI 10.2217/NPY.12.53 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 020YU UT WOS:000309853300008 PM 23397446 ER PT J AU Cortese, S Vincenzi, B Angriman, M AF Cortese, Samuele Vincenzi, Brenda Angriman, Marco TI Identifying and managing sleep disorders associated with ADHD SO NEUROPSYCHIATRY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; RESTLESS LEGS SYNDROME; RANDOMIZED CONTROLLED-TRIAL; LIMB MOVEMENT-DISORDER; SCHOOL-AGED CHILDREN; DAYTIME SLEEPINESS; ONSET INSOMNIA; MELATONIN TREATMENT; DEPRESSED-PATIENTS AB Although often overlooked, sleep disturbances are frequent in ADHD, affecting a sizable proportion of patients. Sleep complaints in patients with ADHD may be due to behavioral factors (e.g., limit-setting disorder), as well as objective alterations, such as delayed sleep-phase disorder, restless legs syndrome, sleep-disordered breathing and the effect of stimulants or associated comorbid disorders. We suggest to systematically screen for sleep disturbances at each visit by means of subjective tools (i.e., questionnaires and sleep diaries) and, when indicated, objective measures (i.e., polysomnography, actigraphy and the multiple sleep latency test). Empirical evidence for the treatment of sleep disturbances associated with ADHD is limited. Besides initial studies on behavioral interventions, the largest and best available evidence demonstrates the effectiveness and good tolerability of melatonin for sleep-onset delay. Further randomized controlled trials of pharmacological and nonpharmacological interventions are needed. C1 [Cortese, Samuele] NYU, Langone Med Ctr, Ctr Child Study, Phyllis Green & Randolph Cowen Inst Pediat Neuros, New York, NY 10016 USA. [Cortese, Samuele] Univ Verona, Dept Life Sci & Reprod, GB Rossi Hosp, Child Neuropsychiat Unit, I-37100 Verona, Italy. [Cortese, Samuele] Univ Tours, Univ Hosp, Child Psychiat Ctr, UMR S INSERM U 930,ERL 3106, Tours, France. [Vincenzi, Brenda] Massachusetts Gen Hosp, Freedom Trail Clin, Boston, MA 02114 USA. [Angriman, Marco] Cent Hosp Bolzano, Dept Pediat, Child Neurol & Neurorehabil Unit, Bolzano, Italy. RP Cortese, S (reprint author), NYU, Langone Med Ctr, Ctr Child Study, Phyllis Green & Randolph Cowen Inst Pediat Neuros, 1 Pk Ave,8th Floor, New York, NY 10016 USA. EM samuele.cortese@gmail.com NR 74 TC 0 Z9 0 U1 4 U2 16 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1758-2008 EI 1758-2016 J9 NEUROPSYCHIATRY-LOND JI Neuropsychiatry PD OCT PY 2012 VL 2 IS 5 BP 393 EP 405 DI 10.2217/NPY.12.49 PG 13 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 020YU UT WOS:000309853300009 ER PT J AU Estevez, AO Mueller, CL Morgan, KL Szewczyk, NJ Teece, L Miranda-Vizuete, A Estevez, M AF Estevez, Annette O. Mueller, Catherine L. Morgan, Kathleen L. Szewczyk, Nathaniel J. Teece, Luke Miranda-Vizuete, Antonio Estevez, Miguel TI Selenium induces cholinergic motor neuron degeneration in Caenorhabditis elegans SO NEUROTOXICOLOGY LA English DT Article DE Cholinergic; Glutathione; Neurodegeneration; Oxidative stress; Selenium ID AMYOTROPHIC-LATERAL-SCLEROSIS; VESICULAR ACETYLCHOLINE TRANSPORTER; EGG-LAYING BEHAVIOR; SYNAPTIC-TRANSMISSION; C-ELEGANS; NEUROMUSCULAR-JUNCTION; PARKINSONS-DISEASE; SODIUM SELENATE; NERVOUS-SYSTEM; RAT MODEL AB Selenium is an essential micronutrient required for cellular antioxidant systems, yet at higher doses it induces oxidative stress. Additionally, in vertebrates environmental exposures to toxic levels of selenium can cause paralysis and death. Here we show that selenium-induced oxidative stress leads to decreased cholinergic signaling and degeneration of cholinergic neurons required for movement and egg-laying in Caenorhabditis elegans. Exposure to high levels of selenium leads to proteolysis of a soluble muscle protein through mechanisms suppressible by two pharmacological agents, levamisole and aldicarb which enhance cholinergic signaling in muscle. In addition, animals with reduction-of-function mutations in genes encoding post-synaptic levamisole-sensitive acetylcholine receptor subunits or the vesicular acetylcholine transporter developed impaired forward movement faster during selenium-exposure than normal animals, again confirming that selenium reduces cholinergic signaling. Finally, the antioxidant reduced glutathione, inhibits selenium-induced reductions in egg-laying through a cellular protective mechanism dependent on the C. elegans glutaredoxin, GLRX-21. These studies provide evidence that the environmental toxicant selenium induces neurodegeneration of cholinergic neurons through depletion of glutathione, a mechanism linked to the neuropathology of Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease. (C) 2012 Elsevier Inc. All rights reserved. C1 [Estevez, Annette O.; Mueller, Catherine L.; Teece, Luke; Estevez, Miguel] Univ Arizona, Dept Neurol, Tucson, AZ 85724 USA. [Morgan, Kathleen L.] Vet Affairs Pittsburgh Healthcare Syst, Res & Dev 151U, Pittsburgh, PA 15240 USA. [Szewczyk, Nathaniel J.] Univ Nottingham, MRC, Arthrit Res UK Ctr Musculoskeletal Ageing Res, Sch Grad Entry Med & Hlth, Derby DE22 3DT, England. [Miranda-Vizuete, Antonio] Univ Seville, Inst Biomed Sevilla, Hosp Univ Virgen Rocio, CSIC, Seville 41013, Spain. [Teece, Luke] Brandeis Univ, Dept Biol, Waltham, MA 02453 USA. [Teece, Luke] Brandeis Univ, Dept Math, Waltham, MA 02453 USA. [Teece, Luke] Brandeis Univ, Dept Psychol, Waltham, MA 02453 USA. RP Estevez, M (reprint author), Univ Arizona, Dept Neurol, 1501N Campbell Ave, Tucson, AZ 85724 USA. EM aestevez@email.arizona.edu; clm58@email.arizona.edu; kathleen@immunetrics.com; Nathaniel.Szewczyk@nottingham.ac.uk; lteece89@brandeis.edu; amiranda-ibis@us.es; estevezm@email.arizona.edu RI Miranda-Vizuete, Antonio/D-6927-2012; IBIS, FISIOLOGIA/O-9485-2015; OI Miranda-Vizuete, Antonio/0000-0002-6856-5396; Szewczyk, Nathaniel/0000-0003-4425-9746 FU Jim Himelic Foundation; Southern Arizona Foundation; Keatings Institute; National Institute of Environmental Health Sciences [R21-ES012305]; National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01-AR054342]; Instituto de Salud Carlos III [PI050065, PI080557]; Fondo Social Europeo, FEDER; Junta de Andalucia [CVI-3629, CVI-2697]; NIH National Center for Research Resources (NCRR) FX We would like to thank LA. Jacobson and D. Miller for providing strains PJ727 and NC571, respectively. This research was supported by grants from the Jim Himelic Foundation (AE and ME), Southern Arizona Foundation (ME), Keatings Institute (ME), National Institutes of Environmental Health Sciences [R21-ES012305 to AE and ME], Arthritis and Musculoskeletal and Skin Diseases [R01-AR054342 to NJS], Instituto de Salud Carlos III [Projects PI050065 and PI080557, co-financed by Fondo Social Europeo, FEDER to AMV] and Junta de Andalucia [Projects CVI-3629 and CVI-2697 to AMV]. Some nematode strains used in this work were provided by the Caenorhabditis Genetics Center, which is funded by the NIH National Center for Research Resources (NCRR). NR 66 TC 25 Z9 25 U1 0 U2 23 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD OCT PY 2012 VL 33 IS 5 BP 1021 EP 1032 DI 10.1016/j.neuro.2012.04.019 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 028BA UT WOS:000310396600006 PM 22560997 ER PT J AU Maserejian, NN Trachtenberg, FL Hauser, R McKinlay, S Shrader, P Bellinger, DC AF Maserejian, Nancy N. Trachtenberg, Felicia L. Hauser, Russ McKinlay, Sonja Shrader, Peter Bellinger, David C. TI Dental composite restorations and neuropsychological development in children: Treatment level analysis from a randomized clinical trial SO NEUROTOXICOLOGY LA English DT Article DE Composite dental resin; Composite resins; Bisphenol A-glycidyl methacrylate; Compomers; Child development; Neuropsychological tests; Executive function; Epidemiology; Prospective studies ID BISPHENOL-A EXPOSURE; AMALGAM TRIAL; PERINATAL EXPOSURE; IN-VIVO; RESIN; RELEASE; MICE; MONOMERS; BEHAVIOR; COMPONENTS AB Background: Resin-based dental restorations may intra-orally release their components and bisphenol A. Gestational bisphenol A exposure has been associated with poorer executive functioning in children. Objectives: To examine whether exposure to resin-based composite restorations is associated with neuropsychological development in children. Methods: Secondary analysis of treatment level data from the New England Children's Amalgam Trial, a 2-group randomized safety trial conducted from 1997 to 2006. Children (N = 534) aged 6-10 y with >= 2 posterior tooth caries were randomized to treatment with amalgam or resin-based composites (bisphenol-A-diglycidyl-dimethacrylate-composite for permanent teeth; urethane dimethacrylate-based polyacid-modified compomer for primary teeth). Neuropsychological function at 4- and 5-year follow-up (N = 444) was measured by a battery of tests of executive function, intelligence, memory, visual-spatial skills, verbal fluency, and problem-solving. Multivariable generalized linear regression models were used to examine the association between composite exposure levels and changes in neuropsychological test scores from baseline to follow-up. For comparison, data on children randomized to amalgam treatment were similarly analyzed. Results: With greater exposure to either dental composite material, results were generally consistent in the direction of slightly poorer changes in tests of intelligence, achievement or memory, but there were no statistically significant associations. For the four primary measures of executive function, scores were slightly worse with greater total composite exposure, but statistically significant only for the test of Letter Fluency (10-surface-years beta = -0.8, SE = 0.4, P = 0.035), and the subtest of color naming (beta = -1.5, SE = 0.5, P = 0.004) in the Stroop Color-Word Interference Test. Multivariate analysis of variance confirmed that the negative associations between composite level and executive function were not statistically significant (MANOVA, P = 0.18). Results for greater amalgam exposure were mostly nonsignificant in the opposite direction of slightly improved scores over follow-up. Conclusions: Dental composite restorations had statistically insignificant associations of small magnitude with impairments in neuropsychological test change scores over 4- or 5-years of follow-up in this trial. (C) 2012 Elsevier Inc. All rights reserved. C1 [Maserejian, Nancy N.; Trachtenberg, Felicia L.; McKinlay, Sonja; Shrader, Peter] New England Res Inst, Watertown, MA 02472 USA. [Hauser, Russ; Bellinger, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Hauser, Russ] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bellinger, David C.] Childrens Hosp Boston, Dept Neurol, Boston, MA 02115 USA. [Bellinger, David C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Maserejian, NN (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM nmaserejian@neriscience.com; ftrachtenberg@neriscience.com; rhauser@hohp.harvard.edu; smckinlay@neriscience.com; pshrader@neriscience.com; David.Bellinger@childrens.harvard.edu FU National Institute of Environmental Health Sciences (NIEHS) [R01ES019155]; New England Research Institutes [U01 DE11886]; National Institute of Dental and Craniofacial Research (NIDCR) [U01 DE11886] FX The analyses presented in this paper were funded by Award Number R01ES019155 from the National Institute of Environmental Health Sciences (NIEHS). The NIEHS had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. The data collection was supported by a cooperative agreement (U01 DE11886) between the New England Research Institutes and the National Institute of Dental and Craniofacial Research (NIDCR), both of which participated in the design and conduct of the New England Children's Amalgam Trial, including collection and management of data. The NIDCR had no role in the analyses or interpretation of data for this manuscript, or in the preparation, review, or approval of the manuscript. The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Environmental Health Sciences, the National Institute of Dental and Craniofacial Research, or the National Institutes of Health. Trial Registration: clinicaltrials.gov Identifier: NCT00065988. NR 55 TC 15 Z9 17 U1 3 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD OCT PY 2012 VL 33 IS 5 BP 1291 EP 1297 DI 10.1016/j.neuro.2012.08.001 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 028BA UT WOS:000310396600034 PM 22906860 ER PT J AU Alford, MD McGregor, JC Singh, H AF Alford, Mariah D. McGregor, Jessina C. Singh, Harleen TI The effects of universal fibrate discontinuation on management of dyslipidemia at the Portland Veterans Affairs Medical Center (PVAMC) SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Annual Meeting of the American-College-of-Clinical-Pharmacy (ACCP) CY OCT 21-24, 2012 CL Hollywood, FL SP Amer Coll Clin Pharm (ACCP) C1 [Alford, Mariah D.] Portland VA Med Ctr, Portland, OR USA. [McGregor, Jessina C.; Singh, Harleen] Oregon Hlth & Sci Univ, Coll Pharm, Oregon State Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD OCT PY 2012 VL 32 IS 10 MA 36 BP E188 EP E188 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 015NH UT WOS:000309452700037 ER PT J AU Patel, K Alsip, D Raval, R Lee, T AF Patel, Khyati Alsip, Danielle Raval, Roshani Lee, Todd TI Comparing change in hemoglobin A1C of patients in pharmacist managed telehealth clinic versus in-person clinic SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Annual Meeting of the American-College-of-Clinical-Pharmacy (ACCP) CY OCT 21-24, 2012 CL Hollywood, FL SP Amer Coll Clin Pharm (ACCP) C1 [Patel, Khyati; Alsip, Danielle; Raval, Roshani] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. [Lee, Todd] Univ Illinois, Coll Pharm, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD OCT PY 2012 VL 32 IS 10 MA 254 BP E253 EP E253 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 015NH UT WOS:000309452700254 ER PT J AU Moshiri, M Chapman, T Fechner, PY Dubinsky, TJ Shnorhavorian, M Osman, S Bhargava, P Katz, DS AF Moshiri, Mariam Chapman, Teresa Fechner, Patricia Y. Dubinsky, Theodore J. Shnorhavorian, Margarett Osman, Sherif Bhargava, Puneet Katz, Douglas S. TI Evaluation and Management of Disorders of Sex Development: Multidisciplinary Approach to a Complex Diagnosis SO RADIOGRAPHICS LA English DT Article ID CONGENITAL ADRENAL-HYPERPLASIA; AMBIGUOUS GENITALIA; CONSENSUS STATEMENT; INTERSEX DISORDERS; GENDER DYSPHORIA; DEVELOPMENT DSD; PERINEOSCROTAL HYPOSPADIAS; INITIAL MANAGEMENT; 46,XY DISORDERS; DIFFERENTIATION AB Various disorders of sex development (DSD) result in abnormal development of genitalia, which may be recognized at prenatal ultrasonography, immediately after birth, or later in life. Current methods for diagnosing DSD include a thorough physical examination, laboratory tests to determine hormone levels and identify chromosomal abnormalities, and radiologic imaging of the genitourinary tract and adjacent organs. Because of the complex nature of DSD, the participation of a multidisciplinary team is required to address the patient's medical needs as well as any psychosocial issues that the patient or the family may encounter after the diagnosis. The first step in the management of DSD is sex assignment, which is based on factors such as the genotype; the presence, location, and appearance of reproductive organs; the potential for fertility; and the cultural background and beliefs of the patient's family. The primary goal of sex assignment is to achieve the greatest possible consistency between the patient's assigned sex and his or her gender identity. Once the sex is assigned, the next step in management might be surgery, hormone therapy, or no intervention at all. Patients with ovotesticular DSD and gonadal dysgenesis may require a gonadectomy, followed by reconstructive surgery. Some patients may need hormone replacement therapy during puberty. An understanding of the immediacy of families' need for sex assignment and clinicians' need for reliable diagnostic imaging results will help radiologists participate effectively in the prenatal and postnatal assessment of patients with DSD. (C)RSNA, 2012 . radiographics.rsna.org C1 [Moshiri, Mariam; Chapman, Teresa; Fechner, Patricia Y.; Dubinsky, Theodore J.; Osman, Sherif; Bhargava, Puneet] Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA. [Chapman, Teresa] Seattle Childrens Hosp, Dept Radiol, Seattle, WA USA. [Fechner, Patricia Y.] Seattle Childrens Hosp, Dept Endocrinol, Seattle, WA USA. [Shnorhavorian, Margarett] Seattle Childrens Hosp, Dept Urol, Seattle, WA USA. [Bhargava, Puneet] VA Puget Sound Hlth Care Syst, Dept Radiol, Seattle, WA USA. [Katz, Douglas S.] Winthrop Univ Hosp, Dept Radiol, Mineola, NY 11501 USA. RP Moshiri, M (reprint author), Univ Washington, Sch Med, Dept Radiol, Box 357115,1959 NE Pacific St, Seattle, WA 98195 USA. EM moshiri@uw.edu OI Bhargava, Puneet/0000-0002-3849-9666 NR 45 TC 7 Z9 14 U1 0 U2 14 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD OCT PY 2012 VL 32 IS 6 SI SI BP 1599 EP 1618 DI 10.1148/rg.326125507 PG 20 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 025PF UT WOS:000310202800006 PM 23065160 ER PT J AU Caterino, JM Ting, SA Sisbarro, SG Espinola, JA Camargo, CA AF Caterino, Jeffrey M. Ting, Sarah A. Sisbarro, Sarah G. Espinola, Janice A. Camargo, Carlos A., Jr. TI Age, Nursing Home Residence, and Presentation of Urinary Tract Infection in U.S. Emergency Departments, 2001-2008 SO ACADEMIC EMERGENCY MEDICINE LA English DT Article ID ASYMPTOMATIC BACTERIURIA; DIAGNOSIS; CRITERIA; MANAGEMENT; FEATURES; PEOPLE; COHORT; WOMEN; STRIP; UTI AB ACADEMIC EMERGENCY MEDICINE 2012; 19:11731180 (C) 2012 by the Society for Academic Emergency Medicine Abstract Objectives: Current outpatient diagnostic algorithms for urinary tract infection (UTI) in older adults require the presence of classic signs and symptoms of UTI, such as fever and genitourinary symptoms. However, older adults with UTI may present with atypical signs and symptoms. The objective was to identify the associations of age and nursing home status with the clinical presentation of emergency department (ED) patients diagnosed with UTI. Methods: This was a retrospective, cross-sectional analysis of the 20012008 National Hospital Ambulatory Medical Care Survey (NHAMCS), ED component. Participants were adult ED patients diagnosed with UTI. Outcome variables were presence of fever, altered mental status, and urinary tract symptoms. Multivariable logistic regression models were constructed for each outcome. Age and nursing home status were the independent variables of interest. Age was divided into adults 18 to 64 years, older adults 65 to 84 years, and oldest adults 85 years of age and older. Results: There were 25.4 million ED visits in which UTI was diagnosed from 2001 through 2008, including 5.0 million in older adults and 2.2 million in the oldest adults. Fever was present in 13% of adults, 21% of older adults, and 19% of the oldest adults. Altered mental status was present in 1% of adults, 7% of older adults, and 13% of the oldest adults. Urinary tract symptoms were identified in 32% of adults, 24% of older adults, and 17% of the oldest adults. In multivariable analysis, altered mental status was more common in older adults (odds ratio [OR] = 1.94) and in the oldest adults (OR = 2.49). Urinary tract symptoms were less common in older adults (OR = 0.60) and the oldest adults (OR = 0.48). Nursing home residence was associated with increased fever (OR = 1.63) and altered mental status (OR = 4.79) and with decreased urinary tract symptoms (OR = 0.35). Conclusions: Fever and urinary tract symptoms are absent in a large proportion of adults over 65 years of age diagnosed with UTI in the ED. Age over 65 years and nursing home residence are associated with increased presence of altered mental status and with lack of urinary tract symptoms. Nursing home residence is also associated with increased presence of fever. Emergency physicians (EPs) continue to diagnose UTI in patients without classic symptoms. Diagnostic criteria for UTI among adults 65 years and over specifically designed for use in the acute care setting should be developed and validated to prevent both inappropriate overdiagnosis and underdiagnosis of UTI. C1 [Caterino, Jeffrey M.; Sisbarro, Sarah G.] Ohio State Univ, Dept Emergency Med, Columbus, OH 43210 USA. [Ting, Sarah A.; Espinola, Janice A.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Caterino, JM (reprint author), Ohio State Univ, Dept Emergency Med, Columbus, OH 43210 USA. EM jeffrey.caterino@osumc.edu RI Caterino, Jeffrey/E-2859-2011 FU American Geriatrics Society; John A. Hartford Foundation; Atlantic Philanthropies FX This project was supported, in part, by a Dennis W. Jahnigen Career Development Scholar Award (JMC) from the American Geriatrics Society, John A. Hartford Foundation, and Atlantic Philanthropies. NR 21 TC 9 Z9 9 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD OCT PY 2012 VL 19 IS 10 BP 1173 EP 1180 DI 10.1111/j.1553-2712.2012.01452.x PG 8 WC Emergency Medicine SC Emergency Medicine GA 023UK UT WOS:000310061200007 PM 23067019 ER PT J AU Pelaz, B Jaber, S de Aberasturi, DJ Wulf, V Aida, T de la Fuente, JM Feldmann, J Gaub, HE Josephson, L Kagan, CR Kotov, NA Liz-Marzan, LM Mattoussi, H Mulvaney, P Murray, CB Rogach, AL Weiss, PS Willner, I Parak, WJ AF Pelaz, Beatriz Jaber, Sarah de Aberasturi, Dorleta Jimenez Wulf, Verena Aida, Takuzo de la Fuente, Jesus M. Feldmann, Jochen Gaub, Hermann E. Josephson, Lee Kagan, Cherie R. Kotov, Nicholas A. Liz-Marzan, Luis M. Mattoussi, Hedi Mulvaney, Paul Murray, Christopher B. Rogach, Andrey L. Weiss, Paul S. Willner, Itamar Parak, Wolfgang J. TI The State of Nanoparticle-Based Nanoscience and Biotechnology: Progress, Promises, and Challenges SO ACS NANO LA English DT Article ID COLLOIDAL SEMICONDUCTOR NANOCRYSTALS; SCANNING TUNNELING MICROSCOPE; CLUSTER-ASSEMBLED MATERIALS; RESONANCE ENERGY-TRANSFER; INTENSE OPTICAL-ACTIVITY; QUANTUM DOTS; GOLD NANOPARTICLES; MAGNETIC NANOPARTICLES; INORGANIC NANOPARTICLES; PARTICLE-SIZE AB Colloidal nanoparticles (NPs) have become versatile building blocks in a wide variety of fields. Here, we discuss the state-of-the-art, current hot topics, and future directions based on the following aspects: narrow size-distribution NPs can exhibit protein-like properties; monodispersity of NPs is not always required; assembled NPs can exhibit collective behavior; NPs can be assembled one by one; there is more to be connected with NPs; NPs can be designed to be smart; surface-modified NPs can directly reach the cytosols of living cells. C1 [Pelaz, Beatriz; de Aberasturi, Dorleta Jimenez; Wulf, Verena; Parak, Wolfgang J.] Univ Marburg, Fachbereich Phys, D-35037 Marburg, Germany. [Pelaz, Beatriz; de Aberasturi, Dorleta Jimenez; Wulf, Verena; Parak, Wolfgang J.] Univ Marburg, WZMW, D-35037 Marburg, Germany. [Pelaz, Beatriz; de la Fuente, Jesus M.] Univ Zaragoza, Inst Nanociencia Aragon, Zaragoza 50018, Spain. [Jaber, Sarah; Mulvaney, Paul] Univ Melbourne, Sch Chem, Parkville, Vic 3010, Australia. [Jaber, Sarah; Mulvaney, Paul] Univ Melbourne, Bio Inst 21, Parkville, Vic 3010, Australia. [de Aberasturi, Dorleta Jimenez] Univ Basque Country, Dept Inorgan Chem, Bilbao 48940, Spain. [Aida, Takuzo] Univ Tokyo, Dept Chem & Biotechnol, Sch Engn, Bunkyo Ku, Tokyo 1138656, Japan. [Feldmann, Jochen; Gaub, Hermann E.] Univ Munich, Dept Phys, D-80799 Munich, Germany. [Feldmann, Jochen; Gaub, Hermann E.] Univ Munich, Ctr NanoSci, D-80799 Munich, Germany. [Josephson, Lee] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. [Josephson, Lee] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Kagan, Cherie R.] Univ Penn, Dept Elect & Syst Engn, Philadelphia, PA 19104 USA. [Kagan, Cherie R.; Murray, Christopher B.] Univ Penn, Dept Mat Sci & Engn, Philadelphia, PA 19104 USA. [Kotov, Nicholas A.] Univ Michigan, Dept Chem Engn, Dept Mat Sci & Engn, Dept Biomed Engn,Biointerface Inst, Ann Arbor, MI 48109 USA. [Liz-Marzan, Luis M.] Ctr Cooperat Res Biomat CiC BiomaGUNE, San Sebastian 20009, Spain. [Liz-Marzan, Luis M.] Basque Fdn Sci, Bilbao 48011, Spain. [Mattoussi, Hedi] Florida State Univ, Dept Chem & Biochem, Tallahassee, FL 32306 USA. [Rogach, Andrey L.] City Univ Hong Kong, CFP, Kowloon, Hong Kong, Peoples R China. [Rogach, Andrey L.] City Univ Hong Kong, Dept Phys & Mat Sci, Kowloon, Hong Kong, Peoples R China. [Weiss, Paul S.] Univ Calif Los Angeles, Dept Chem & Biochem, Dept Mat Sci & Engn, Los Angeles, CA 90095 USA. [Weiss, Paul S.] Univ Calif Los Angeles, Calif NanoSyst Inst, Los Angeles, CA 90095 USA. [Willner, Itamar] Hebrew Univ Jerusalem, Inst Chem, Ctr Nanosci & Nanotechnol, IL-91904 Jerusalem, Israel. RP Parak, WJ (reprint author), Univ Marburg, Fachbereich Phys, Renthof 5, D-35037 Marburg, Germany. EM wolfgang.parak@physik.uni-marburg.de RI Weiss, Paul/A-2575-2011; Aida, Takuzo/I-9117-2012; Liz-Marzan, Luis/B-8910-2011; Parak, Wolfgang J./M-3998-2014; Jimenez de Aberasturi, Dorleta/G-8365-2015; Pelaz, Beatriz/I-7703-2015; biomaGUNE, CIC/J-9136-2014; OI de la Fuente, Jesus M/0000-0003-1081-8482; Weiss, Paul/0000-0001-5527-6248; Liz-Marzan, Luis/0000-0002-6647-1353; Parak, Wolfgang J./0000-0003-1672-6650; Jimenez de Aberasturi, Dorleta/0000-0001-5009-3557; Pelaz, Beatriz/0000-0002-4626-4576; biomaGUNE, CIC/0000-0001-7690-0660; Kotov, Nicholas/0000-0002-6864-5804 FU DFG [PA 794/11-1]; ERC; ARAID FX This article was inspired by reports at the NANAX5 conference held in Fuengirola, Spain, May 7-11, 2012. Parts of this work were funded by DFG PA 794/11-1 (to W.J.P.), ERC-Starting Grant Nanopuzzle and ARAID (to J.M.F.), and ERC-Advanced Grant PLASMAQUO (to L.M.L.M.). ERC Advanced Investigator grant HYMEM (J.F.) is acknowledged NR 164 TC 116 Z9 117 U1 20 U2 319 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 J9 ACS NANO JI ACS Nano PD OCT PY 2012 VL 6 IS 10 BP 8468 EP 8483 DI 10.1021/nn303929a PG 16 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 024FW UT WOS:000310096100002 PM 23016700 ER PT J AU King, DR Ogilvie, MP Velmahos, G Alam, HB deMoya, MA Wilcox, SR Mejaddam, AY Van der Wilden, GM Birkhan, OA Fikry, K AF King, David R. Ogilvie, Michael P. Velmahos, George Alam, Hasan B. deMoya, Marc A. Wilcox, Susan R. Mejaddam, Ali Y. Van der Wilden, Gwendolyn M. Birkhan, Oscar A. Fikry, Karim TI Emergent cricothyroidotomies for trauma: training considerations SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID AIRWAY MANAGEMENT; DIFFICULT AIRWAY; CRICOTHYROTOMY; RESIDENCY AB Background: Emergent cricothyroidotomy remains an uncommon, but life-saving, core procedural training requirement for emergency medicine (EM) physician training. We hypothesized that although most cricothyroidotomies for trauma occur in the emergency department (ED), they are usually performed by surgeons. Methods: We conducted a retrospective analysis of all emergent cricothyroidotomies for trauma presentations performed at 2 large level I trauma centers over 10 years. Operators and assistants for all procedures were identified, as well as mechanism of injury and patient demographics were examined. Results: Fifty-four cricothyroidotomies were analyzed. Patients had a mean age of 50 years, 80% were male, and 90% presented as a result of blunt trauma. The most common primary operator was a surgeon (n = 47, 87%), followed by an emergency medical services (EMS) provider (n = 6, 11%) and an EM physician (n = 1, 2%). In all cases, except those performed by EMS, the operator or assistant was an attending surgeon. All EMS procedures resulted in serious complications compared with in-hospital procedures (P < .0001). Conclusions: (1) Prehospital cricothyroidotomy results in serious complications. (2) Despite the ubiquitous presence of EM physicians in the ED, all cricothyroidotomies were performed by a surgeon, which may present opportunities for training improvement. (c) 2012 Elsevier Inc. All rights reserved. C1 [King, David R.; Velmahos, George; Alam, Hasan B.; deMoya, Marc A.; Mejaddam, Ali Y.; Van der Wilden, Gwendolyn M.; Birkhan, Oscar A.; Fikry, Karim] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [King, David R.; Velmahos, George; Alam, Hasan B.; deMoya, Marc A.; Mejaddam, Ali Y.; Van der Wilden, Gwendolyn M.; Birkhan, Oscar A.; Fikry, Karim] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Ogilvie, Michael P.] Univ Miami, Sch Med, Div Trauma Surg, Jackson Mem Hosp,Ryder Trauma Ctr, Miami, FL 33136 USA. [Wilcox, Susan R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wilcox, Susan R.] Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. RP King, DR (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. EM dking3@partners.org OI Wilcox, Susan/0000-0001-7477-7531; King, David/0000-0003-1028-1478 NR 16 TC 6 Z9 7 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD OCT PY 2012 VL 30 IS 8 BP 1429 EP 1432 DI 10.1016/j.ajem.2011.10.026 PG 4 WC Emergency Medicine SC Emergency Medicine GA 020MI UT WOS:000309813900016 PM 22205011 ER PT J AU Sharma, AK Heist, EK Ferrell, M AF Sharma, Ajay K. Heist, E. Kevin Ferrell, Margaret TI Treatment for ST-elevation myocardial infarction-bronchoscopy! SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID SEGMENT ELEVATION; ISCHEMIA; THERAPY; TRIAL; SIZE AB ST elevation is usually treated in cardiac catheterization laboratory with an aim for myocardial salvage by restoration of adequate coronary blood flow enhancing both early and long-term survival. Maximum benefit is achieved if therapy is initiated in the first hour after treatment onset, thus ushering the concept of door-to-balloon time. We present an interesting case of a patient whose ST elevation resolved after bronchoscopy for a lung whiteout. C1 [Sharma, Ajay K.] Charlton Mem Hosp, Dept Internal Med, Fall River, MA USA. [Heist, E. Kevin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA USA. [Ferrell, Margaret] Charlton Mem Hosp, Dept Cardiol, Fall River, MA USA. RP Sharma, AK (reprint author), Charlton Mem Hosp, Dept Internal Med, Fall River, MA USA. EM ajayrattan12@gmail.com NR 10 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD OCT PY 2012 VL 30 IS 8 AR 1660.e1 DI 10.1016/j.ajem.2011.08.018 PG 4 WC Emergency Medicine SC Emergency Medicine GA 020MI UT WOS:000309813900068 PM 22033388 ER PT J AU Strate, LL Modi, R Cohen, E Spiegel, BMR AF Strate, Lisa L. Modi, Rusha Cohen, Erica Spiegel, Brennan M. R. TI Diverticular Disease as a Chronic Illness: Evolving Epidemiologic and Clinical Insights SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID IRRITABLE-BOWEL-SYNDROME; SIGMOID DIVERTICULITIS; COLONIC DIVERTICULOSIS; PRACTICE PARAMETERS; DIGESTIVE DISEASES; SEGMENTAL COLITIS; DIETARY FIBER; UNITED-STATES; RISK-FACTORS; BURDEN AB Diverticular disease imposes a significant burden on Western and industrialized societies. The traditional pathogenesis model posits that low dietary fiber predisposes to diverticulosis, and fecalith obstruction prompts acute diverticulitis that is managed with broad-spectrum antibiotics or surgery. However, a growing body of knowledge is shifting the paradigm of diverticular disease from an acute surgical illness to a chronic bowel disorder composed of recurrent abdominal symptoms and considerable psychosocial impact. New research implicates a role for low-grade inflammation, sensory-motor nerve damage, and dysbiosis in a clinical picture that mimics irritable bowel syndrome (IBS) and even inflammatory bowel disease (IBD). Far from being an isolated event, acute diverticulitis may be the catalyst for chronic symptoms including abdominal pain, cramping, bloating, diarrhea, constipation, and "post-diverticulitis IBS." In addition, studies reveal lower health-related quality of life in patients with chronic diverticular disease vs. controls. Health-care providers should maintain a high index of suspicion for the multifaceted presentations of diverticular disease, and remain aware that it might contribute to long-term emotional distress beyond traditional diverticulitis attacks. These developments are prompting a shift in therapeutic approaches from widespread antimicrobials and supportive care to the use of probiotics, mesalamine, and gut-directed antibiotics. This review addresses the emerging literature regarding epidemiology, pathophysiology, and management of chronic, symptomatic diverticular disease, and provides current answers to common clinical questions. C1 [Strate, Lisa L.] Univ Washington, Harborview Med Ctr, Sch Med, Div Gastroenterol,Dept Med, Seattle, WA 98104 USA. [Modi, Rusha; Spiegel, Brennan M. R.] Univ Calif Los Angeles, VA Ctr Outcomes Res & Educ, Los Angeles, CA USA. [Cohen, Erica; Spiegel, Brennan M. R.] VA Greater Los Angeles Healthcare Syst, Dept Med, Div Gastroenterol, Los Angeles, CA USA. [Spiegel, Brennan M. R.] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Dept Med, Los Angeles, CA 90095 USA. [Spiegel, Brennan M. R.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. RP Spiegel, BMR (reprint author), 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu FU Amgen; Ironwood Pharmaceuticals; Shire Pharmaceuticals FX Brennan Spiegel has served as an advisor for Prometheus and Ironwood Pharmaceuticals, and has received research support from Amgen, Ironwood Pharmaceuticals, and Shire Pharmaceuticals. Lisa Strate has served as an advisor for Shire Pharmaceuticals. NR 69 TC 79 Z9 79 U1 2 U2 32 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2012 VL 107 IS 10 BP 1486 EP 1493 DI 10.1038/ajg.2012.194 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 018XK UT WOS:000309701000007 PM 22777341 ER PT J AU Kanwal, F Hoang, T Kramer, J Chrusciel, T El-Serag, H Dominitz, JA Asch, SM AF Kanwal, Fasiha Tuyen Hoang Kramer, Jennifer Chrusciel, Timothy El-Serag, Hashem Dominitz, Jason A. Asch, Steven M. TI The Performance of Process Measures in Hepatitis C SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID VIRUS-INFECTION; ANTIVIRAL THERAPY; LIVER-DISEASE; UNITED-STATES; US VETERANS; RIBAVIRIN; VACCINATION; PREDICTORS; MANAGEMENT AB OBJECTIVES: Previous evaluations regarding the extent to which standard chronic hepatitis C virus (HCV) care processes are delivered during routine clinical care are scant and have primarily relied on automated data-the validity of which is unknown. METHODS: We examined adherence to 24 explicit modified Delphi panel-derived HCV-specific process measures in a cohort of 122,744 patients enrolled in the automated Veterans Administration HCV Clinical Case Registry between 2000 and 2006. We reviewed medical charts of 717 patients to compare the agreement between Registry and charts. We also estimated the effect of justifiable exceptions on measured performance in HCV by determining the proportion of patients who failed a measure but met a valid exception (i.e., patient refusal, outside care, or treatment contraindications). RESULTS: The percentage of patients who met the individual measures varied. For example, 74% of patients received HCV genotype testing, 23% received antiviral treatment, 28% received liver biopsy, and 16% received hepatitis A vaccination. We found excellent agreement between the Registry and charts in all measures (agreement coefficients >0.75). However, exceptions to indicated care documented in charts were common for genotype testing, liver biopsy, and antiviral treatment. After accounting for these exceptions, the measure rates increased from 75 to 93% for genotype testing, 31 to 50% for liver biopsy, and from 26 to 64% for antiviral treatment. Treatment contraindications were the most common reasons for not meeting indicated care. CONCLUSIONS: Automated data missed several exceptions to care that are documented only in providers' notes, thus underestimating process of care. These results have implications for future quality assessment initiatives-most of which will likely rely on automated data for process-based quality reporting. After accounting for automated data and medical record reviews, vaccinations and antiviral treatment rates in the Veterans Administration left room for improvement. C1 [Kanwal, Fasiha; Chrusciel, Timothy] St Louis Univ, John Cochran VA Med Ctr, Dept Gastroenterol & Hepatol, St Louis, MO 63103 USA. [Kanwal, Fasiha] St Louis Univ, Sch Med, St Louis, MO USA. [Tuyen Hoang; Asch, Steven M.] Greater Los Angeles VA Healthcare Syst, Dept Med, Los Angeles, CA USA. [Kanwal, Fasiha; Kramer, Jennifer; El-Serag, Hashem] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston VA HSR&D Ctr Excellence, Hlth Serv Res & Dev Serv, Houston, TX 77030 USA. [Kramer, Jennifer; El-Serag, Hashem] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Kramer, Jennifer; El-Serag, Hashem] Baylor Coll Med, Dept Med, Gastroenterol Sect, Houston, TX 77030 USA. [Dominitz, Jason A.] VA Puget Healthcare Syst, NW VA Hepatitis Resource Ctr C, Seattle, WA USA. [Asch, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Kanwal, F (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston VA HSR&D Ctr Excellence, Hlth Serv Res & Dev Serv, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM fasiha.kanwal@va.gov OI Dominitz, Jason/0000-0002-8070-7086 FU Health Services Research and Development Service, Office of Research and Development, Department of Veterans Affairs [IIR-07-111] FX This material is based on work supported part by Health Services Research and Development Service, Office of Research and Development, Department of Veterans Affairs, grant IIR-07-111 to Dr Kanwal. We are indebted to the Hepatitis C Clinical Case Registry for the data used in this study. The authors declare no conflict of interest. NR 26 TC 12 Z9 12 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2012 VL 107 IS 10 BP 1512 EP 1521 DI 10.1038/ajg.2012.201 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 018XK UT WOS:000309701000010 PM 22777337 ER PT J AU Laine, L Jensen, DM McQuaid, KR AF Laine, Loren Jensen, Dennis M. McQuaid, Kenneth R. TI Is Injecting Absolute Alcohol a Safe and Effective Therapy for Bleeding Ulcers? Response SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Letter C1 [Laine, Loren] Yale Univ, Sch Med, Sect Digest Dis, New Haven, CT 06520 USA. [Laine, Loren] VA Connecticut Healthcare Syst, New Haven, CT USA. [Jensen, Dennis M.] Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [McQuaid, Kenneth R.] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. RP Laine, L (reprint author), Yale Univ, Sch Med, Sect Digest Dis, 333 Cedar St,1080 LMP, New Haven, CT 06520 USA. EM loren.laine@yale.edu NR 2 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2012 VL 107 IS 10 BP 1591 EP 1591 DI 10.1038/ajg.2012.258 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 018XK UT WOS:000309701000026 ER PT J AU Patel, SS Burns, TL Botto, LD Riehle-Colarusso, TJ Lin, AE Shaw, GM The, PAR AF Patel, Sonali S. Burns, Trudy L. Botto, Lorenzo D. Riehle-Colarusso, Tiffany J. Lin, Angela E. Shaw, Gary M. The, Paul A. Romitti CA Natl Birth Defects Prevention Stud TI Analysis of Selected Maternal Exposures and Non-Syndromic Atrioventricular Septal Defects in the National Birth Defects Prevention Study, 1997-2005 SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE atrioventricular septal defect; defect; endocardial cushion; atrioventricular canal defect; heart defects; congenital; risk factors; cigarette smoking; secondhand smoke exposure ID CONGENITAL HEART-DEFECTS; CARDIOVASCULAR MALFORMATIONS; MEDICATION USE; RISK-FACTORS; TOBACCO-SMOKE; UNITED-STATES; PREGNANCY; DISEASE; PREVALENCE; POLYMORPHISMS AB Although the descriptive epidemiology of atrioventricular septal defects (AVSDs), a group of serious congenital heart defects (CHDs), has been recently reported, non-genetic risk factors have not been consistently identified. Using data (1997-2005) from the National Birth Defects Prevention Study, an ongoing multisite population-based case-control study, the association between selected non-genetic factors and non-syndromic AVSDs was examined. Data on periconceptional exposures to such factors were collected by telephone interview from 187 mothers of AVSD case infants and 6,703 mothers of unaffected infants. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated from logistic regression models. Mothers who reported cigarette smoking during the periconceptional period were more likely to have infants with AVSDs compared with non-smokers, independent of maternal age, periconceptional alcohol consumption, infant gestational age, family history of CHDs, and study site (aOR 1.5, 95% CI 1.1-2.4). The association was strongest in mothers who smoked more than 25 cigarettes/day. In addition, mothers with periconceptional passive smoke exposure were more likely to have infants with AVSDs than unexposed mothers, independent of maternal age, active periconceptional smoking, infant gestational age, and family history of CHDs (aOR 1.4, 95% CI 1.0-2.0). No associations were observed between AVSDs and maternal history of a urinary tract infection or pelvic inflammatory disease, maternal use of a wide variety of medications, maternal occupational exposure, parental drug use, or maternal alcohol consumption. If the results of this preliminary study can be replicated, minimizing maternal active and passive smoke exposure may decrease the incidence of AVSDs. (C) 2012 Wiley Periodicals, Inc. C1 [Patel, Sonali S.; Burns, Trudy L.] Univ Iowa, Carver Coll Med, Dept Pediat, Iowa City, IA 52242 USA. [Burns, Trudy L.; The, Paul A. Romitti] Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Iowa City, IA 52242 USA. [Botto, Lorenzo D.] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA. [Riehle-Colarusso, Tiffany J.] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA USA. [Lin, Angela E.] Massachusetts Ctr Birth Defects Res & Prevent, Massachusetts Dept Publ Hlth, Boston, MA USA. [Lin, Angela E.] MassGen Hosp Children, Genet Unit, Boston, MA USA. [Shaw, Gary M.] Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA. RP Patel, SS (reprint author), Univ Iowa, Childrens Hosp, Dept Pediat, Div Pediat Cardiol, 200 Hawkins Dr, Iowa City, IA 52242 USA. EM sonali-patel@uiowa.edu FU Centers for Disease Control and Prevention [U01/DD000492]; Slone Epidemiology Center of Boston University FX Grant sponsor: Centers for Disease Control and Prevention; Grant number: U01/DD000492; Grant sponsor: Slone Epidemiology Center of Boston University. NR 46 TC 18 Z9 19 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD OCT PY 2012 VL 158A IS 10 BP 2447 EP 2455 DI 10.1002/ajmg.a.35555 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 023XK UT WOS:000310070700012 PM 22903798 ER PT J AU Ku, JH Ali, A Suhler, EB Choi, D Rosenbaum, JT AF Ku, Jennifer H. Ali, Amro Suhler, Eric B. Choi, Dongseok Rosenbaum, James T. TI Characteristics and Visual Outcome of Patients With Retinal Vasculitis SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID UVEITIS AB Objective: To examine the characteristics and visual outcome in 207 patients with retinal vasculitis. Methods: Demographic and visual outcome data were collected retrospectively from the ophthalmologic records of 207 cases (321 affected eyes). Descriptive analysis was performed on all cases and visual outcome analysis was performed for the 114 cases with visual acuity recorded at 2 or more visits. The Kaplan-Meier method and Cox regression were used to examine visual outcome and predictors for prognosis. Results: Patients in our series had a roughly even distribution of sex, were predominantly non-Hispanic white (77.8%), and had bilateral disease (75.7%). The annualized mean visual acuity change for the 203 eyes (114 patients) with some follow-up was 0.01 logMAR unit per year. Although 75 eyes (36.9%) had 20/25 or better visual acuity at baseline, 33.6% of the remaining eyes experienced visual acuity improvement of at least 2 lines on the Snellen chart during follow-up and some continued to improve more than 9 years after the initial evaluation. Cox multivariate analysis demonstrated that patients who were nonwhite, had worse visual acuity at baseline, or who had an ocular infection were more likely to experience improvement by this definition. Conclusions: We believe that this is the first US case series to investigate visual outcome in patients with this diagnosis. Although many patients in our series worsened despite therapy, a subset experienced substantial improvement. C1 [Ku, Jennifer H.] Oregon Hlth & Sci Univ, Casey Eye Inst, Dept Ophthalmol, Portland, OR 97239 USA. [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Ku, Jennifer H.; Suhler, Eric B.; Choi, Dongseok] Oregon Hlth & Sci Univ, Dept Publ Hlth, Portland, OR 97239 USA. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. RP Ku, JH (reprint author), Oregon Hlth & Sci Univ, Casey Eye Inst, Dept Ophthalmol, 3181 Sam Jackson Pk Rd SW, Portland, OR 97239 USA. EM kuj@ohsu.edu FU Research to Prevent Blindness; National Eye Institute; Stan and Madelle Rosenfeld Family Trust; William and Mary Bauman Foundation; William C. Kuzell Foundation FX This work was supported by Research to Prevent Blindness, a core grant from the National Eye Institute, and funds from the Stan and Madelle Rosenfeld Family Trust, the William and Mary Bauman Foundation, and the William C. Kuzell Foundation. NR 16 TC 3 Z9 3 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD OCT PY 2012 VL 130 IS 10 BP 1261 EP 1266 DI 10.1001/archophthalmol.2012.1596 PG 6 WC Ophthalmology SC Ophthalmology GA 016TX UT WOS:000309543500002 PM 22688383 ER PT J AU Parver, DL Dreher, RJ Kohanim, S Zimmerman, P Garrett, G Devisetty, L Pasquale, LR AF Parver, David L. Dreher, Robert J. Kohanim, Sahar Zimmerman, Paul Garrett, Geoffrey Devisetty, Laxmi Pasquale, Louis R. TI Ocular Injury After Laser Hair Reduction Treatment to the Eyebrow SO ARCHIVES OF OPHTHALMOLOGY LA English DT Editorial Material ID IRIS ATROPHY; EPILATION; COMPLICATIONS; REMOVAL C1 [Parver, David L.; Devisetty, Laxmi] Georgetown Univ, Washington Natl Eye Ctr, Washington, DC USA. [Kohanim, Sahar; Pasquale, Louis R.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Zimmerman, Paul] Univ Utah, Moran Eye Ctr, Salt Lake City, UT USA. [Garrett, Geoffrey] Louisiana State Univ, Hlth Sci Ctr, Dept Ophthalmol, Shreveport, LA 71105 USA. RP Parver, DL (reprint author), Retina Consultants PC, 1145 19th St NW, Washington, DC 20036 USA. EM dparver@yahoo.com NR 11 TC 2 Z9 2 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD OCT PY 2012 VL 130 IS 10 BP 1330 EP 1334 PG 6 WC Ophthalmology SC Ophthalmology GA 016TX UT WOS:000309543500016 PM 23044952 ER PT J AU Butler, NJ Suhler, EB AF Butler, Nicholas J. Suhler, Eric B. TI Levofloxacin-Associated Panuveitis With Chorioretinal Lesions SO ARCHIVES OF OPHTHALMOLOGY LA English DT Letter C1 [Butler, Nicholas J.] Johns Hopkins Univ, Sch Med, Div Ocular Immunol, Wilmer Eye Inst, Baltimore, MD 21287 USA. [Suhler, Eric B.] Oregon Hlth & Sci Univ, Casey Eye Inst, Portland, OR 97201 USA. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. RP Butler, NJ (reprint author), Johns Hopkins Univ, Sch Med, Div Ocular Immunol, Wilmer Eye Inst, 1800 Orleans St,Woods Bldg,Room 472, Baltimore, MD 21287 USA. EM nbutle10@jhmi.edu NR 4 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD OCT PY 2012 VL 130 IS 10 BP 1342 EP 1344 PG 4 WC Ophthalmology SC Ophthalmology GA 016TX UT WOS:000309543500021 PM 23044958 ER PT J AU Kyung, SEE Yoon, MK Crawford, JB Horton, JC AF Kyung, Sung-eun E. Yoon, Michael K. Crawford, J. Brooks Horton, Jonathan C. TI Florid Arteritis Confined to a Single Branch of the Superficial Temporal Artery SO ARCHIVES OF OPHTHALMOLOGY LA English DT Letter ID GIANT-CELL ARTERITIS; BIOPSY C1 [Horton, Jonathan C.] Univ Calif San Francisco, Beckman Vis Ctr, Dept Ophthalmol, San Francisco, CA 94143 USA. [Crawford, J. Brooks; Horton, Jonathan C.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Crawford, J. Brooks; Horton, Jonathan C.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. [Yoon, Michael K.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Kyung, Sung-eun E.] Dankook Univ, Sch Med, Dept Ophthalmol, Cheonan, South Korea. RP Horton, JC (reprint author), Univ Calif San Francisco, Beckman Vis Ctr, Dept Ophthalmol, 10 Koret Way, San Francisco, CA 94143 USA. EM hortonj@vision.ucsf.edu NR 6 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD OCT PY 2012 VL 130 IS 10 BP 1347 EP 1348 PG 2 WC Ophthalmology SC Ophthalmology GA 016TX UT WOS:000309543500023 PM 23044960 ER PT J AU Blashill, AJ Powlishta, KK AF Blashill, Aaron J. Powlishta, Kimberly K. TI Effects of Gender-Related Domain Violations and Sexual Orientation on Perceptions of Male and Female Targets: An Analogue Study SO ARCHIVES OF SEXUAL BEHAVIOR LA English DT Article DE Sexual orientation; Sexual prejudice; Gender role violations; Masculinity; Femininity; Gender atypicality ID GAY MEN; UNITED-STATES; BISEXUAL POPULATIONS; ATTITUDES; LESBIANS; PREJUDICE; HEALTH; HOMOSEXUALITY; DISCRIMINATION; STEREOTYPES AB The current study examined factors that influenced heterosexual male and female raters' evaluations of male and female targets who were gay or heterosexual, and who displayed varying gender roles (i.e., typical vs. atypical) in multiple domains (i.e., activities, traits, and appearance). Participants were 305 undergraduate students from a private, midwestern Jesuit institution who read vignettes describing one of 24 target types and then rated the target on possession of positive and negative characteristics, psychological adjustment, and on measures reflecting the participants' anticipated behavior toward or comfort with the target. Results showed that gender atypical appearance and activity attributes (but not traits) were viewed more negatively than their gender typical counterparts. It was also found that male participants in particular viewed gay male targets as less desirable than lesbian and heterosexual male targets. These findings suggest a nuanced approach for understanding sexual prejudice, which incorporates a complex relationship among sex, gender, sexual orientation, and domain of gendered attributes. C1 [Blashill, Aaron J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Powlishta, Kimberly K.] St Louis Univ, Dept Psychol, St Louis, MO 63103 USA. RP Blashill, AJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM ablashill@partners.org NR 40 TC 6 Z9 6 U1 0 U2 8 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0004-0002 J9 ARCH SEX BEHAV JI Arch. Sex. Behav. PD OCT PY 2012 VL 41 IS 5 BP 1293 EP 1302 DI 10.1007/s10508-012-9971-1 PG 10 WC Psychology, Clinical; Social Sciences, Interdisciplinary SC Psychology; Social Sciences - Other Topics GA 024AU UT WOS:000310080600024 PM 22722956 ER PT J AU Gurses, AP Kim, G Martinez, EA Marsteller, J Bauer, L Lubomski, LH Pronovost, PJ Thompson, D AF Gurses, Ayse P. Kim, George Martinez, Elizabeth A. Marsteller, Jill Bauer, Laura Lubomski, Lisa H. Pronovost, Peter J. Thompson, David TI Identifying and categorising patient safety hazards in cardiovascular operating rooms using an interdisciplinary approach: a multisite study SO BMJ QUALITY & SAFETY LA English DT Article ID BYPASS GRAFT-SURGERY; CARDIAC-SURGERY; ADVERSE EVENTS; CARE; ERRORS; SYSTEM; INTERVENTION; INFECTIONS; GUIDELINES; FAILURES AB Background: Cardiac surgery is a complex, high-risk procedure with potential vulnerabilities for patient safety. The evidence base describing safety hazards in the cardiovascular operating room is underdeveloped but is essential to guide future safety improvement efforts. Objective: To identify and categorise hazards (anything that has the potential to cause a preventable adverse patient safety event) in the cardiovascular operating room. Methods: An interdisciplinary team of researchers used prospective methods, including direct observations, contextual inquiry and photographs to collect hazard data pertaining to the cardiac surgery perioperative period, which started immediately before the patient was transferred to the operating room and ended immediately after patient handoff to the post-anaesthesia/intensive care unit. Data were collected between February and September 2008 in five hospitals. An interdisciplinary approach that included a human factors and systems engineering framework was used to guide the study. Results: Twenty cardiac surgeries including the corresponding handoff processes from operating room to post-anaesthesia/intensive care unit were observed. A total of 58 categories of hazards related to care providers (eg, practice variations), tasks (eg, high workload), tools and technologies (eg, poor usability), physical environment (eg, cluttered workspace), organisation (eg, hierarchical culture) and processes (eg, non-compliance with guidelines) were identified. Discussion: Hazards in cardiac surgery services are ubiquitous, indicating numerous opportunities to improve safety. Future efforts should focus on creating a stronger culture of safety in the cardiovascular operating room, increasing compliance with evidence-based infection control practices, improving communication and teamwork, and developing a partnership among all stakeholders to improve the design of tools and technologies. C1 [Gurses, Ayse P.; Kim, George; Marsteller, Jill; Lubomski, Lisa H.; Pronovost, Peter J.; Thompson, David] Johns Hopkins Univ, Sch Med, Armstrong Inst Patient Safety & Qual, Baltimore, MD USA. [Gurses, Ayse P.; Kim, George; Marsteller, Jill; Bauer, Laura; Lubomski, Lisa H.; Pronovost, Peter J.; Thompson, David] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA. [Gurses, Ayse P.; Kim, George] Johns Hopkins Univ, Sch Med, Div Hlth Sci Informat, Baltimore, MD USA. [Gurses, Ayse P.; Marsteller, Jill; Pronovost, Peter J.] Johns Hopkins Univ, Dept Hlth Policy & Management, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA. [Martinez, Elizabeth A.] Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA. [Marsteller, Jill] Johns Hopkins Univ, Ctr Hlth Serv & Outcomes Res, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Pronovost, Peter J.; Thompson, David] Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA. [Pronovost, Peter J.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. RP Gurses, AP (reprint author), 1909 Thames St,2nd Floor, Baltimore, MD 21231 USA. EM agurses1@jhmi.edu FU Society of Cardiovascular Anaesthesiologists Foundation (SCAF) as part of their FOCUS Initiative; SCA Foundation; Agency for Healthcare Research and Quality [HS018762, HS013904- 02]; National Patient Safety Foundation; National Council of State Boards of Nursing; Michigan Health & Hospital Association Keystone Center for Quality and Patient Safety; Society for Paediatric Anaesthesia; Agency for Healthcare Research and Quality; National Institutes of Health; Robert Wood Johnson Foundation; Commonwealth Fund FX The research was funded in part by the Society of Cardiovascular Anaesthesiologists Foundation (SCAF) as part of their FOCUS Initiative. The FOCUS Initiative is a collaborative project of the Society of Cardiovascular Anaesthesiologists, the SCA Foundation, and the Johns Hopkins University Quality and Safety Research Group. FOCUS is funded exclusively by the SCA Foundation; the following received support for this research: Drs Marsteller, Pronovost, Gurses, Lubomski and Thompson, and Ms Bauer. Ayse P Gurses was supported in part by the Agency for Healthcare Research and Quality K01 grant no. HS018762. Elizabeth A Martinez was supported by the Agency for Healthcare Research and Quality K08 grant no. HS013904- 02.; Dr Gurses reports receiving grant or contract support from the National Patient Safety Foundation, consulting fees from a grant funded by the National Council of State Boards of Nursing, and an honorarium from a healthcare system for speaking at a patient safety workshop. Dr Lubomski reports receiving funding from the Michigan Health & Hospital Association Keystone Center for Quality and Patient Safety, and consultancy fees from the Society for Paediatric Anaesthesia. Dr Thompson was supported by the SCA Foundation, but has no other conflicts to report. Dr Pronovost reports receiving grant or contract support from the Agency for Healthcare Research and Quality, the National Institutes of Health, the Robert Wood Johnson Foundation, and The Commonwealth Fund for research related to measuring and improving patient safety; honoraria from various hospitals and healthcare systems and the Leigh Bureau to speak on quality and safety; consultancy with the Association for Professionals in Infection Control and Epidemiology, Inc; and book royalties for authoring Safe Patients, Smart Hospitals: How One Doctor's Checklist Can Help Us Change Health Care from the Inside Out. NR 40 TC 31 Z9 31 U1 1 U2 16 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD OCT PY 2012 VL 21 IS 10 BP 810 EP 818 DI 10.1136/bmjqs-2011-000625 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 016JK UT WOS:000309513900002 PM 22562873 ER PT J AU Bechard, LJ Feldman, HA Venick, R Gura, K Gordon, C Sonis, A Mehta, N Guinan, EC Duggan, C AF Bechard, L. J. Feldman, H. A. Venick, R. Gura, K. Gordon, C. Sonis, A. Mehta, N. Guinan, E. C. Duggan, C. TI Attenuation of resting energy expenditure following hematopoietic SCT in children SO BONE MARROW TRANSPLANTATION LA English DT Article DE parenteral nutrition; energy expenditure; energy balance; indirect calorimetry ID BONE-MARROW-TRANSPLANTATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; TOTAL PARENTERAL-NUTRITION; STEM-CELL TRANSPLANTATION; CRITICALLY-ILL CHILDREN; INDIRECT CALORIMETRY; BODY-COMPOSITION; CHILDHOOD-CANCER; ADULT SURVIVORS; DOUBLE-BLIND AB Children undergoing hematopoietic SCT (HSCT) typically receive parenteral nutrition (PN) due to gastrointestinal toxicities. Accurate determination of resting energy expenditure (REE) may facilitate optimal energy provision and help avoid unintended overfeeding or underfeeding. A multicenter, prospective cohort study of children undergoing allogeneic HSCT was performed, in which REE was measured by indirect calorimetry at baseline and twice weekly until 30 days after transplantation. Change in percent predicted REE over time from admission was analyzed using repeated measures regression analysis. In all, 26 children (14 females) with a mean (s.d.) age of 14.9 (4.2) years who underwent an HLA-matched sibling or unrelated donor transplantation were enrolled. Mean (s.d.) percent predicted REE at baseline was 92.4 (15.2). Baseline REE was highly correlated with lean body mass measured by dual energy X-ray absorptiometry (r=0.78, P<0.0001). REE decreased significantly over time, following a quadratic curve to a nadir of 79% predicted at 14 days post transplantation (P<0.001) and returned to near baseline by day 30. Children undergoing HSCT exhibit a significant reduction in REE in the early weeks after transplantation, a phenomenon that places them at risk for overfeeding. Serial measurements of REE or reductions in energy intake should be considered when PN is the primary mode of nutrition. C1 [Bechard, L. J.] Childrens Hosp, Clin Nutr Serv, Boston, MA 02115 USA. [Bechard, L. J.; Guinan, E. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Venick, R.] Univ Calif Los Angeles, Mattel Childrens Hosp, Los Angeles, CA USA. RP Bechard, LJ (reprint author), Childrens Hosp, Clin Nutr Serv, 300 Longwood Ave, Boston, MA 02115 USA. EM lori.bechard@childrens.harvard.edu RI Mehta, Nilesh/G-7073-2016 FU Massachusetts Vitamin Litigation Grant; NCRR [M01-RR02172]; NIH [UL1 RR025758-01, M01-RR00865, K24 HD 058795] FX We appreciate the dedication and support of all the participants, and the helpful assistance of Nicolle Quinn, MS, RD, LDN and Patricia Jardack, MS, RD. This project was supported by the Massachusetts Vitamin Litigation Grant; grant M01-RR02172 from the NCRR, the NIH to Children's Hospital, Boston GCRC; grant UL1 RR025758-01 to the Harvard Catalyst CTSA 1; grant M01-RR00865 to the General Clinical Research Centers Program at UCLA; and NIH K24 HD 058795 (CD). NR 43 TC 4 Z9 4 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD OCT PY 2012 VL 47 IS 10 BP 1301 EP 1306 DI 10.1038/bmt.2012.19 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 022KG UT WOS:000309957700007 PM 22343669 ER PT J AU Liou, AP Turnbaugh, PJ AF Liou, Alice P. Turnbaugh, Peter J. TI Antibiotic Exposure Promotes Fat Gain SO CELL METABOLISM LA English DT Editorial Material ID MICROBIOME AB Recent research suggests that obesity may be influenced not only by dietary and genetic risk factors, but also by the trillions of microorganisms inhabiting our gastrointestinal tract. Consistent with this notion, Cho et al. (2012) use mice to demonstrate that subtherapeutic antibiotic treatment promotes adiposity. C1 [Turnbaugh, Peter J.] Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA. [Liou, Alice P.] Massachusetts Gen Hosp, Obes Nutr & Metab Inst, Boston, MA 02114 USA. RP Turnbaugh, PJ (reprint author), Harvard Univ, FAS Ctr Syst Biol, Cambridge, MA 02138 USA. EM pturnbaugh@fas.harvard.edu OI Turnbaugh, Peter/0000-0002-0888-2875 FU NIDDK NIH HHS [F32 DK095561]; NIGMS NIH HHS [P50 GM068763] NR 9 TC 2 Z9 2 U1 1 U2 19 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD OCT PY 2012 VL 16 IS 4 BP 408 EP 410 DI 10.1016/j.cmet.2012.09.009 PG 3 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 022HK UT WOS:000309948400002 PM 23040064 ER PT J AU Yusuf, RZ Scadden, DT AF Yusuf, Rushdia Zareen Scadden, David T. TI Fate through Fat: Lipid Metabolism Determines Stem Cell Division Outcome SO CELL METABOLISM LA English DT Editorial Material ID HYPOXIC-NICHE; LEVEL AB Distinctive metabolism associated with particular cell states is increasingly being defined in normal and malignant cells. Ito et al. (2012) now show that fatty acid oxidation is associated with hematopoietic stem cells and determines whether they undergo symmetric or asymmetric cell division, driving a fundamental property of the stem cell state. C1 [Yusuf, Rushdia Zareen; Scadden, David T.] Harvard Univ, Harvard Stem Cell Inst, Massachusetts Gen Hosp, Ctr Regenerat Med, Cambridge, MA 02138 USA. [Yusuf, Rushdia Zareen; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Scadden, DT (reprint author), Harvard Univ, Harvard Stem Cell Inst, Massachusetts Gen Hosp, Ctr Regenerat Med, Cambridge, MA 02138 USA. EM david_scadden@harvard.edu FU NHLBI NIH HHS [R01 HL044851, U01 HL100402] NR 10 TC 6 Z9 6 U1 1 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD OCT PY 2012 VL 16 IS 4 BP 411 EP 413 DI 10.1016/j.cmet.2012.09.011 PG 3 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 022HK UT WOS:000309948400004 PM 23040066 ER PT J AU So, JS Hur, KY Tarrio, M Ruda, V Frank-Kamenetsky, M Fitzgerald, K Koteliansky, V Lichtman, AH Iwawaki, T Glimcher, LH Lee, AH AF So, Jae-Seon Hur, Kyu Yeon Tarrio, Margarite Ruda, Vera Frank-Kamenetsky, Maria Fitzgerald, Kevin Koteliansky, Victor Lichtman, Andrew H. Iwawaki, Takao Glimcher, Laurie H. Lee, Ann-Hwee TI Silencing of Lipid Metabolism Genes through IRE1 alpha-Mediated mRNA Decay Lowers Plasma Lipids in Mice SO CELL METABOLISM LA English DT Article ID UNFOLDED PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM STRESS; BOX-BINDING PROTEIN-1; FATTY LIVER-DISEASE; ER STRESS; TRANSMEMBRANE PROTEIN; INSULIN-RESISTANCE; KINASE ACTIVATION; LDL-CHOLESTEROL; MOUSE MODELS AB XBP1 is a key regulator of the unfolded protein response (UPR), which is involved in a wide range of physiological and pathological processes. XBP1 ablation in liver causes profound hypolipidemia in mice, highlighting its critical role in lipid metabolism. XBP1 deficiency triggers feedback activation of its upstream enzyme IRE1 alpha, instigating regulated IRE1-dependent decay (RIDD) of cytosolic mRNAs. Here, we identify RIDD as a crucial control mechanism of lipid homeostasis. Suppression of RIDD by RNA interference or genetic ablation of IRE1 alpha reversed hypolipidemia in XBP1-deficient mice. Comprehensive microarray analysis of XBP1 and/or IRE1 alpha-deficient liver identified genes involved in lipogenesis and lipoprotein metabolism as RIDD substrates, which might contribute to the suppression of plasma lipid levels by activated IRE1 alpha. Ablation of XBP1 ameliorated hepatosteatosis, liver damage, and hypercholesterolemia in dyslipidemic animal models, suggesting that direct targeting of either IRE1 alpha or XBP1 might be a feasible strategy to treat dyslipidemias. C1 [So, Jae-Seon; Hur, Kyu Yeon; Glimcher, Laurie H.; Lee, Ann-Hwee] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Tarrio, Margarite; Lichtman, Andrew H.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Ruda, Vera] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Ruda, Vera] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Ruda, Vera] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Frank-Kamenetsky, Maria; Fitzgerald, Kevin; Koteliansky, Victor] Alnylam Pharmaceut, Cambridge, MA 02142 USA. [Iwawaki, Takao] RIKEN, Iwawaki Initiat Res Unit, Wako, Saitama 3510198, Japan. [Iwawaki, Takao] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama 3320012, Japan. [Iwawaki, Takao] Gunma Univ, Adv Sci Res Leaders Dev Unit, Gunma 3718511, Japan. [Glimcher, Laurie H.; Lee, Ann-Hwee] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Glimcher, Laurie H.] Ragon Inst MGH MIT & Harvard, Boston, MA 02129 USA. RP Lee, AH (reprint author), Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY 10021 USA. EM anl2042@med.cornell.edu FU NIH [AI32412, DK082448, DK089211]; American Heart Association; Bristol-Myers Squibb Company FX This study was supported by NIH grants AI32412 (L.H.G.), DK082448 (L.H.G.), and DK089211 (A.-H.L.) and by grants from the American Heart Association (A.-H.L.) and Bristol-Myers Squibb Company (A.-H.L.). We thank David Cohen for FPLC and helpful discussions; Richard Lehner for TGH (Ces1) antibody; Kirsten Sigrist for help with animal maintenance; and Wen-Pin Yang, Aiqing He, Bo Guan, and David Gordon for microarray analysis. We also thank Brian Bettencort and Greg Hinkle (design and bioinformatics); Akin Akinc and Alnylam formulations group; and Muthiah Manoharan, Martin Maier, Satya Kumchimanchi, Klaus Charisse, William Querbes, and the rest of the Alnylam chemistry team for siRNA synthesis. L.H.G. is a member of the board of directors of and holds equity in Bristol Myers Squibb. NR 54 TC 75 Z9 80 U1 2 U2 13 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD OCT PY 2012 VL 16 IS 4 BP 487 EP 499 DI 10.1016/j.cmet.2012.09.004 PG 13 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 022HK UT WOS:000309948400011 PM 23040070 ER PT J AU Paek, J Lo, JY Narasimhan, SD Nguyen, TN Glover-Cutter, K Robida-Stubbs, S Suzuki, T Yamamoto, M Blackwell, TK Curran, SP AF Paek, Jennifer Lo, Jacqueline Y. Narasimhan, Sri Devi Nguyen, Tammy N. Glover-Cutter, Kira Robida-Stubbs, Stacey Suzuki, Takafumi Yamamoto, Masayuki Blackwell, T. Keith Curran, Sean P. TI Mitochondrial SKN-1/Nrf Mediates a Conserved Starvation Response SO CELL METABOLISM LA English DT Article ID OXIDATIVE-STRESS-RESPONSE; CAENORHABDITIS-ELEGANS; C-ELEGANS; LIFE-SPAN; LONGEVITY; PROTEIN; NRF2; RESTRICTION; GROWTH; SPECIFICATION AB SKN-1/Nrf plays multiple essential roles in development and cellular homeostasis. We demonstrate that SKN-1 executes a specific and appropriate transcriptional response to changes in available nutrients, leading to metabolic adaptation. We isolated gain-of-function (gf) alleles of skn-1, affecting a domain of SKN-1 that binds the transcription factor MXL-3 and the mitochondrial outer membrane protein PGAM-5. These skn-1(gf) mutants perceive a state of starvation even in the presence of plentiful food. The aberrant monitoring of cellular nutritional status leads to an altered survival response in which skn-1(gf) mutants transcriptionally activate genes associated with metabolism, adaptation to starvation, aging, and survival. The triggered starvation response is conserved in mice with constitutively activated Nil and may contribute to the tumorgenicity associated with activating Nil mutations in mammalian somatic cells. Our findings delineate an evolutionarily conserved metabolic axis of SKN-1/Nrf, further establishing the complexity of this pathway. C1 [Paek, Jennifer; Nguyen, Tammy N.; Curran, Sean P.] Univ So Calif, Leonard Davis Sch Gerontol, Los Angeles, CA 90089 USA. [Lo, Jacqueline Y.; Curran, Sean P.] Univ So Calif, Dept Mol & Computat Biol, Coll Letters Arts & Sci, Los Angeles, CA 90089 USA. [Narasimhan, Sri Devi; Glover-Cutter, Kira; Robida-Stubbs, Stacey; Blackwell, T. Keith] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Joslin Diabet Ctr, Boston, MA 02114 USA. [Narasimhan, Sri Devi; Glover-Cutter, Kira; Robida-Stubbs, Stacey; Blackwell, T. Keith] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Suzuki, Takafumi; Yamamoto, Masayuki] Tohoku Univ, Sch Med, Aoba Ku, Sendai, Miyagi 9808575, Japan. [Curran, Sean P.] Univ So Calif, Dept Biochem & Mol Biol, Keck Sch Med, Los Angeles, CA 90089 USA. RP Curran, SP (reprint author), Univ So Calif, Leonard Davis Sch Gerontol, Los Angeles, CA 90089 USA. EM spcurran@usc.edu RI Yamamoto, Masayuki/A-4873-2010; OI Glover-Cutter, Kira/0000-0002-7321-8604 FU NIH [R01GM62891, R00AG032308] FX We thank Chandra Tucker, Duke University for the C. elegans Y2H library (Developed by Maureen Barr's laboratory). We are grateful to Daniel Wai, Children's Hospital Los Angeles for analysis of Affymetrix microarray data. We also thank Drs. Caleb Finch, Alexander Soukas, and Shanshan Pang for critically reading the manuscript and all members of the Curran laboratory for technical support and fruitful discussions. S.P.C. conceived and designed the study. T.K.B. and M.Y. collaborated with SPC to plan and organize experiments. J.P., J.Y.L., S.D.N., T.N.N., K.G.C., S.R.S., T.S., and S.P.C. conducted the experiments. Some of the strains used in the study were obtained from the Caenorhabditis Genetics Center (CGC), which is supported by the National Institutes of Health-NCRR. Research in this study was supported by NIH R01GM62891 (T.K.B.) and R00AG032308 (S.P.C.). S.P.C. is an Ellison Medical Foundation Junior Scholar in Aging. NR 50 TC 47 Z9 52 U1 1 U2 17 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD OCT PY 2012 VL 16 IS 4 BP 526 EP 537 DI 10.1016/j.cmet.2012.09.007 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 022HK UT WOS:000309948400014 PM 23040073 ER PT J AU Lam, AQ Humphreys, BD AF Lam, Albert Q. Humphreys, Benjamin D. TI Onco-Nephrology: AKI in the Cancer Patient SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE-RENAL-FAILURE; HEMATOPOIETIC-CELL TRANSPLANTATION; ACUTE KIDNEY INJURY; BONE-MARROW-TRANSPLANTATION; HEPATIC VENOOCCLUSIVE DISEASE; TUMOR LYSIS SYNDROME; VERSUS-HOST-DISEASE; MULTIPLE-MYELOMA; PLASMA-EXCHANGE; RISK-FACTORS AB AKI is common in patients with cancer, and it causes interruptions in therapy and increased hospital length of stay, cost, and mortality. Although cancer patients are susceptible to all of the usual causes of AKI in patients without cancer, there are a number of AKI syndromes that occur more frequently or are unique to this patient population. AKI also confers substantially increased risk of short-term death, and the ability to reverse AKI portends a better outcome in some cancers, such as multiple myeloma. Several trends in oncology, including increased survival, better supportive care, older patients who have received multiple chemotherapy regimens, and new therapeutic options, are driving an increase in the numbers of cancer patients who develop AKI. As a result, nephrologists should be increasingly familiar with the diagnosis, management, and treatment of AKI in this setting. Here, we summarize recent data on epidemiology of AKI in cancer patients, describe the most common AKI syndromes in this population, and highlight emerging areas in the growing field of onconephrology. Clin J Am Soc Nephrol 7: 1692-1700, 2012. doi: 10.2215/CJN.103140312 C1 [Lam, Albert Q.; Humphreys, Benjamin D.] Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. [Humphreys, Benjamin D.] Dana Farber Canc Inst, Lance Armstrong Fdn Adult Survivorship Clin, Boston, MA 02115 USA. RP Humphreys, BD (reprint author), Harvard Inst Med, Room 554,4 Blackfan Circle, Boston, MA 02115 USA. EM bhumphreys@partners.org FU National Institutes of Health [DK088923] FX B.D.H is supported by National Institutes of Health Grant DK088923. NR 69 TC 20 Z9 21 U1 0 U2 10 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD OCT PY 2012 VL 7 IS 10 BP 1692 EP 1700 DI 10.2215/CJN.03140312 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 023LV UT WOS:000310036800022 PM 22879433 ER PT J AU Zhao, LH Tian, L Uno, H Solomon, SD Pfeffer, MA Schindler, JS Wei, LJ AF Zhao, Lihui Tian, Lu Uno, Hajime Solomon, Scott D. Pfeffer, Marc A. Schindler, Jerald S. Wei, Lee Jen TI Utilizing the integrated difference of two survival functions to quantify the treatment contrast for designing, monitoring, and analyzing a comparative clinical study SO CLINICAL TRIALS LA English DT Article ID KAPLAN-MEIER STATISTICS; CENSORED-DATA; LARGE SAMPLE; TESTS; LIFE; TRIALS; MODEL AB Background Consider a comparative, randomized clinical study with a specific event time as the primary end point. In the presence of censoring, standard methods of summarizing the treatment difference are based on Kaplan-Meier curves, the logrank test, and the point and interval estimates via Cox's procedure. Moreover, for designing and monitoring the study, one usually utilizes an event-driven scheme to determine the sample sizes and interim analysis time points. Purpose When the proportional hazards (PHs) assumption is violated, the logrank test may not have sufficient power to detect the difference between two event time distributions. The resulting hazard ratio estimate is difficult, if not impossible, to interpret as a treatment contrast. When the event rates are low, the corresponding interval estimate for the 'hazard ratio' can be quite large due to the fact that the interval length depends on the observed numbers of events. This may indicate that there is not enough information for making inferences about the treatment comparison even when there is no difference between two groups. This situation is quite common for a postmarketing safety study. We need an alternative way to quantify the group difference. Methods Instead of quantifying the treatment group difference using the hazard ratio, we consider an easily interpretable and model-free parameter, the integrated survival rate difference over a prespecified time interval, as an alternative. We present the inference procedures for such a treatment contrast. This approach is purely nonparametric and does not need any model assumption such as the PHs. Moreover, when we deal with equivalence or noninferiority studies and the event rates are low, our procedure would provide more information about the treatment difference. We used a cardiovascular trial data set to illustrate our approach. Results The results using the integrated event rate differences have a heuristic interpretation for the treatment difference even when the PHs assumption is not valid. When the event rates are low, for example, for the cardiovascular study discussed in this article, the procedure for the integrated event rate difference provides tight interval estimates in contrast to those based on the event-driven inference method. Limitations The design of a trial with the integrated event rate difference may be more complicated than that using the event-driven procedure. One may use simulation to determine the sample size and the estimated duration of the study. Conclusions The procedure discussed in this article can be a useful alternative to the standard PHs method in the survival analysis. Clinical Trials 2012; 9: 570-577. http://ctj.sagepub.com C1 [Uno, Hajime; Wei, Lee Jen] Harvard Univ, Dept Biostat, Boston, MA 02115 USA. [Zhao, Lihui] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA. [Tian, Lu] Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [Uno, Hajime] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Solomon, Scott D.; Pfeffer, Marc A.] Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. [Schindler, Jerald S.] Merck Res Labs, Rahway, NJ USA. RP Wei, LJ (reprint author), Harvard Univ, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA. EM wei@hsph.harvard.edu RI Solomon, Scott/I-5789-2013 FU US National Institutes of Health [R01 AI052817, RC4 CA155940, U01 AI068616, UM1 AI068634, R01 AI024643, U54 LM008748, R01 HL089778] FX This research was partially supported by grants from US National Institutes of Health (R01 AI052817, RC4 CA155940, U01 AI068616, UM1 AI068634, R01 AI024643, U54 LM008748, R01 HL089778). NR 21 TC 13 Z9 13 U1 0 U2 11 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD OCT PY 2012 VL 9 IS 5 BP 570 EP 577 DI 10.1177/1740774512455464 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 019HX UT WOS:000309730200002 PM 22914867 ER PT J AU Ersek, M Polissar, N Du Pen, A Jablonski, A Herr, K Neradilek, MB AF Ersek, Mary Polissar, Nayak Du Pen, Anna Jablonski, Anita Herr, Keela Neradilek, Moni B. TI Addressing methodological challenges in implementing the nursing home pain management algorithm randomized controlled trial SO CLINICAL TRIALS LA English DT Article ID OF-LIFE CARE; ADVANCED DEMENTIA; HIP FRACTURE; PHARMACOLOGICAL MANAGEMENT; IMMPACT RECOMMENDATIONS; COGNITIVE IMPAIRMENT; FAMILY PERSPECTIVES; ASSESSMENT TOOLS; CLINICAL-TRIALS; PERSISTENT PAIN AB Background Unrelieved pain among nursing home (NH) residents is a well-documented problem. Attempts have been made to enhance pain management for older adults, including those in NHs. Several evidence-based clinical guidelines have been published to assist providers in assessing and managing acute and chronic pain in older adults. Despite the proliferation and dissemination of these practice guidelines, research has shown that intensive systems-level implementation strategies are necessary to change clinical practice and patient outcomes within a health-care setting. One promising approach is the embedding of guidelines into explicit protocols and algorithms to enhance decision making. Purpose The goal of the article is to describe several issues that arose in the design and conduct of a study that compared the effectiveness of pain management algorithms coupled with a comprehensive adoption program versus the effectiveness of education alone in improving evidence-based pain assessment and management practices, decreasing pain and depressive symptoms, and enhancing mobility among NH residents. Methods The study used a cluster-randomized controlled trial (RCT) design in which the individual NH was the unit of randomization. The Roger's Diffusion of Innovations theory provided the framework for the intervention. Outcome measures were surrogate-reported usual pain, self-reported usual and worst pain, and self-reported pain-related interference with activities, depression, and mobility. Results The final sample consisted of 485 NH residents from 27 NHs. The investigators were able to use a staggered enrollment strategy to recruit and retain facilities. The adaptive randomization procedures were successful in balancing intervention and control sites on key NH characteristics. Several strategies were successfully implemented to enhance the adoption of the algorithm. Limitations/Lessons The investigators encountered several methodological challenges that were inherent to both the design and implementation of the study. The most problematic issue concerned the measurement of outcomes in persons with moderate to severe cognitive impairment. It was difficult to identify valid, reliable, and sensitive outcome measures that could be applied to all NH residents regardless of the ability to self-report. Another challenge was the inability to incorporate advances in implementation science into the ongoing study Conclusions Methodological challenges are inevitable in the conduct of an RCT. The need to optimize internal validity by adhering to the study protocol is compromised by the emergent logistical issues that arise during the course of the study. Clinical Trials 2012; 9: 634-644. http://ctj.sagepub.com C1 [Ersek, Mary] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. [Ersek, Mary; Neradilek, Moni B.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Polissar, Nayak] Mt Whisper Light Stat, Seattle, WA USA. [Du Pen, Anna] Univ Washington, Sch Med, Dept Family Med, Seattle, WA 98195 USA. [Jablonski, Anita] Seattle Univ, Coll Nursing, Seattle, WA 98122 USA. [Herr, Keela] Univ Iowa, Coll Nursing, Iowa City, IA 52242 USA. RP Ersek, M (reprint author), Univ Penn, Sch Nursing, 418 Curie Blvd,Room 329, Philadelphia, PA 19104 USA. EM ersekm@nursing.upenn.edu FU National Institute of Nursing Research [R01NR009100]; Swedish Medical Center, Seattle, WA; University of Pennsylvania School of Nursing; Philadelphia VA Medical Center FX The project described was supported by Award Number R01NR009100 from the National Institute of Nursing Research.; This material is the result of work supported with resources and the use of facilities at the Swedish Medical Center, Seattle, WA; the University of Pennsylvania School of Nursing; and the Philadelphia VA Medical Center. Mary Ersek conceived the study, procured funding, served as principal investigator of the project, and drafted the manuscript. Nayak Polissar and Moni B Neradilek developed, described, and implemented the randomization procedures, power calculations, and statistical analyses. Anna Du Pen and Keela Herr participated in the study design. Anna Du Pen and Anita Jablonski assisted in coordinating the study and refining the methods. All authors assisted in drafting the manuscript and approved the final manuscript. Clinical trials registration: NCT01399567, Swedish Medical Center, Seattle, WA. NR 73 TC 7 Z9 7 U1 2 U2 18 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD OCT PY 2012 VL 9 IS 5 BP 634 EP 644 DI 10.1177/1740774512454243 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 019HX UT WOS:000309730200012 PM 22879574 ER PT J AU Baran, I Bradley, JA Alipour, F Rosenthal, P Le, HG Jacobs, DS AF Baran, Inna Bradley, James A. Alipour, Fateme Rosenthal, Perry Le, Hong-Gam Jacobs, Deborah S. TI PROSE treatment of corneal ectasia SO CONTACT LENS & ANTERIOR EYE LA English DT Article DE Corneal ectasia; Scleral lens; PROSE; Keratoconus; Prosthetic device ID SCLERAL CONTACT-LENS; QUALITY-OF-LIFE; PENETRATING KERATOPLASTY; REFRACTIVE SURGERY; VISUAL FUNCTION; KERATOCONUS; OUTCOMES; DISEASE; ACUITY; LASER AB Purpose: Prosthetic replacement of the ocular surface ecosystem (PROSE) uses custom designed and fabricated prosthetic devices in a treatment that restores vision, supports healing, reduces symptoms and improves quality of life in patients with complex corneal disease. We report the success rate for PROSE treatment of corneal ectasia. Methods: Records of 59 patients with corneal ectasia seen in consultation over 6 months were reviewed. Candidacy for treatment, topographic indices, change in visual acuity, achievement of satisfactory fit, device wear status and change in visual function at 6 months were recorded. Results: Sixteen eyes were non-candidates because conventional correction was adequate. Trial devices were inserted but not dispensed for 13 eyes. No eyes were excluded for severity of ectasia. In the remaining 89 eyes, satisfactory fit was achieved and a device was dispensed. Twenty-one eyes (15 patients) had undergone penetrating keratoplasty. Device wear at 6 months was documented in 78/89 eyes (88%). NEI VFQ-25 score improved 27.6 points (p < 0.001) on a 100 point scale in patients wearing a device at 6 months. Conclusion: All candidate eyes with corneal ectasia could be fitted with a PROSE device. PROSE treatment has a high success rate when measured by ability to achieve satisfactory fit, impact on visual acuity and 6 month data on both rate of continued wear and impact on visual function. PROSE treatment is an alternative to penetrating keratoplasty for patients with corneal ectasia who are contact lens intolerant. (c) 2012 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved. C1 [Baran, Inna; Bradley, James A.; Alipour, Fateme; Rosenthal, Perry; Le, Hong-Gam; Jacobs, Deborah S.] Boston Fdn Sight, Needham, MA 02494 USA. [Rosenthal, Perry; Jacobs, Deborah S.] Harvard Univ, Sch Med, Boston, MA USA. [Jacobs, Deborah S.] Massachusetts Eye & Ear Infirm, Cornea Serv, Boston, MA 02114 USA. RP Jacobs, DS (reprint author), Boston Fdn Sight, 464 Hillside Ave,Suite 205, Needham, MA 02494 USA. EM djacobs@bostonsight.org NR 39 TC 21 Z9 21 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1367-0484 J9 CONTACT LENS ANTERIO JI Contact Lens Anterior Eye PD OCT PY 2012 VL 35 IS 5 BP 222 EP 227 DI 10.1016/j.clae.2012.04.003 PG 6 WC Ophthalmology SC Ophthalmology GA 021NX UT WOS:000309893400007 PM 22633003 ER PT J AU Larkin, ME Griffith, CA Pitler, L Donahue, L Sbrolla, A AF Larkin, Mary E. Griffith, Catherine A. Pitler, Linda Donahue, Lauren Sbrolla, Amy TI Building Communities of Practice: The Research Nurse Round Table SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE LA English DT Article DE research nursing; specialty practice AB This paper shares the experience of establishing a research nurse forum aimed at knowledge sharing, problem solving, and community building from the perspective of a group of clinical research nurses at Massachusetts General Hospital (MGH), a tertiary care center in Boston, Massachusetts. We report on a sequence of developmental steps taken to create this forum as an example of best practice for research nurses. Logistical considerations, mission and goals, as well as outcomes and implications for practice are described, with the intent that others interested in building similar forums can replicate aspects of this model within their own practice settings. Clin Trans Sci 2012; Volume 5: 428431 C1 [Larkin, Mary E.; Griffith, Catherine A.; Pitler, Linda; Sbrolla, Amy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Donahue, Lauren] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Larkin, ME (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM Mlarkin1@partners.org NR 10 TC 2 Z9 2 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1752-8054 J9 CTS-CLIN TRANSL SCI JI CTS-Clin. Transl. Sci. PD OCT PY 2012 VL 5 IS 5 BP 428 EP 431 DI 10.1111/j.1752-8062.2012.00435.x PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 023YX UT WOS:000310075000010 PM 23067357 ER PT J AU Hanlon, CA Jones, EM Li, XB Hartwell, KJ Brady, KT George, MS AF Hanlon, Colleen A. Jones, E. Morgan Li, Xingbao Hartwell, Karen J. Brady, Kathleen T. George, Mark S. TI Individual variability in the locus of prefrontal craving for nicotine: Implications for brain stimulation studies and treatments SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE Nicotine; Craving; Functional MRI; Transcranial magnetic stimulation ID TRANSCRANIAL MAGNETIC STIMULATION; SMOKING; CORTEX; ABSTINENCE; DEPENDENCE; RELAPSE; FMRI; RTMS; CUES; TMS AB Background: Attenuation of cue-elicited craving with brain stimulation techniques is a growing area of attention in addiction research. This investigation aims to guide these studies by assessing individual variability in the location of peak cortical activity during cue-elicited craving. Method: Twenty-six nicotine-dependent individuals performed a cue-elicited craving task in a 3T MRI scanner while BOLD signal data was collected. The task included epochs of smoking cues, neutral cues, and rest. The location of peak activity during smoking cues relative to neutral cues ('hot spot') was isolated for each individual. The spatial dispersion of the 26 cue-elicited hot spots (1 per participant) was quantified via hierarchical clustering. Results: When viewing nicotine cues all 26 participants had at least one cluster of significant prefrontal cortex activity (p < 0.05, cluster corrected). Only 62% had peak activity in the medial prefrontal cortex cluster (including 100% of the men). In 15% of the participants peak activity was located in either the left lateral prefrontal cortex or left insula cluster. Peak activity in the remaining 23% was dispersed throughout the prefrontal cortex. Conclusion: There is considerable individual variability in the location of the cue-elicited 'hot spot' as measured by BOLD activity. Men appear to have a more uniform location of peak BOLD response to cues than women. Consequently, acquiring individual functional imaging data may be advantageous for either tailoring treatment to the individual or filtering participants before enrollment in treatment. (c) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Hanlon, Colleen A.; Jones, E. Morgan; Li, Xingbao; Hartwell, Karen J.; Brady, Kathleen T.; George, Mark S.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Hartwell, Karen J.; Brady, Kathleen T.; George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. RP Hanlon, CA (reprint author), Med Univ S Carolina, Dept Psychiat, Ctr Adv Imaging Res, Charleston, SC 29425 USA. EM hanlon@musc.edu FU NIDA [K01DA027756]; NICHD [K12HD055885]; MUSC's CTSA from the National Center for Research Resources [UL1 RR029882] FX Funding was provided by NIDA K01DA027756 (Hanlon), NICHD K12HD055885 (Hartwell), and MUSC's CTSA UL1 RR029882 from the National Center for Research Resources. The funding source had no further role in study design, collection, analysis, interpretation or in the decision to submit the paper for publication. NR 25 TC 6 Z9 7 U1 2 U2 16 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD OCT 1 PY 2012 VL 125 IS 3 BP 239 EP 243 DI 10.1016/j.drugalcdep.2012.02.019 PG 5 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 024NL UT WOS:000310115800008 PM 22459915 ER PT J AU Wen, LS Oshiomogho, JI Eluwa, GI Steptoe, AP Sullivan, AF Camargo, CA AF Wen, Leana S. Oshiomogho, John I. Eluwa, George I. Steptoe, Anne P. Sullivan, Ashley F. Camargo, Carlos A., Jr. TI Characteristics and capabilities of emergency departments in Abuja, Nigeria SO EMERGENCY MEDICINE JOURNAL LA English DT Article AB Objectives Emergency departments (ED) are the basic unit of international emergency medicine, but often differ in fundamental features. This study sought to describe and characterise ED in the capital city of Nigeria, Abuja. Methods All ED open 24 h/day 7 days/week to the general public were surveyed using the national ED inventories survey instrument (http://www.emnet-nedi.org). ED staff were asked about ED characteristics with reference to calendar year 2008. Results Twenty-four ED participated (83% response). All were located in hospitals, which ranged in size from six to 250 beds. The majority (92% CI 73% to 100%) had a contiguous layout with medical and surgical care provided in one area. All ED saw both adults and children, with a median of 1500 annual visits (IQR 648-2328). Almost half of respondents (46%; CI 26% to 67%) thought their ED operated under capacity, none thought that their ED was over capacity. Only 4% of ED surveyed had dedicated CT scanners, 25% had cardiac monitoring and none had negative-pressure rooms. There was wide variation in the types of emergencies that were identified as being treatable 24 h/day 7 days/week; these appeared to correlate with ED consultant availability. Conclusions Although ED location and layout in Abuja do not differ greatly from that in a typical US city, ED utilisation was lower and fewer resources and capabilities were available. The lack of technological and human resources raise questions about what critical technologies are needed in resource-limited settings, and whether Nigeria should consider training emergency medicine physicians to meet its workforce needs. C1 [Wen, Leana S.; Oshiomogho, John I.; Steptoe, Anne P.; Sullivan, Ashley F.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Wen, Leana S.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA USA. [Eluwa, George I.] Populat Council, Dept Operat Res, Abuja, Nigeria. [Eluwa, George I.] Diadem Consults, Dept Hlth Policy, Abuja, Nigeria. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org OI Wen, Leana/0000-0003-0259-0537 NR 10 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 1472-0205 J9 EMERG MED J JI Emerg. Med. J. PD OCT PY 2012 VL 29 IS 10 BP 798 EP 801 DI 10.1136/emermed-2011-200695 PG 4 WC Emergency Medicine SC Emergency Medicine GA 020OC UT WOS:000309820200004 PM 22052953 ER PT J AU Wen, LS Nagurney, JT Geduld, HI Wen, AP Wallis, LA AF Wen, Leana S. Nagurney, J. Tobias Geduld, Heike I. Wen, Angela P. Wallis, Lee A. TI Procedure competence versus number performed: a survey of graduate emergency medicine specialists in a developing nation SO EMERGENCY MEDICINE JOURNAL LA English DT Article ID SKILLS AB Background Emergency medicine (EM) training programmes are being conducted around the world but no study has assessed the procedural competence of developing nations' EM trainees. Objectives To quantify the number of core procedures and resuscitations performed and describe the perceived procedural competency of graduates of Africa's first EM registrarship at the University of Cape Town/Stellenbosch University (UCT/SUN) in Cape Town, South Africa. Methods All 30 graduates from the first four classes in the UCT/SUN EM programme (2007-10) were asked to complete a written, self-administered survey on the number of procedures needed for competency, the number of procedures performed during registrarship and the perceived competence in each procedure ranked on a five-point Likert scale. The procedures selected were the 10 core procedures and four types of resuscitations as defined by the US-based Residency Review Committee. Results were compiled and analysed using descriptive statistics. Results Twenty-seven (90%) completed surveys. For most core procedures and all resuscitations, the number of procedures reported by respondents far exceeded the Residency Review Committee minimum. The three procedures not meeting the minimum were internal cardiac pacing, cricothyrotomy and periocardiocentesis. Respondents reported perceived competence in most procedures and all resuscitations. Conclusions EM trainees in a South Africa registrarship report a high number of procedures performed for most procedures and all resuscitations. As medical education moves to the era of direct observation and other methods of assessment, more studies are needed to define and ensure procedural competence in trainees of nascent EM programmes. C1 [Wen, Leana S.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Harvard Affiliated Emergency Med Residency, Dept Emergency Med, Boston, MA 02116 USA. [Geduld, Heike I.; Wallis, Lee A.] Univ Cape Town, Div Emergency Med, ZA-7925 Cape Town, South Africa. [Geduld, Heike I.] Univ Stellenbosch, ZA-7600 Stellenbosch, South Africa. [Wen, Angela P.] Univ So Calif, Dept Biochem & Mol Biol, Los Angeles, CA USA. RP Wen, LS (reprint author), Massachusetts Gen Hosp, Brigham & Womens Hosp, Harvard Affiliated Emergency Med Residency, Dept Emergency Med, 178 Marlborough St 5, Boston, MA 02116 USA. EM wen.leana@gmail.com OI Wen, Leana/0000-0003-0259-0537 FU Partners Healthcare FX LSW received a travel grant from Partners Healthcare to conduct research. NR 14 TC 0 Z9 0 U1 0 U2 8 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1472-0205 J9 EMERG MED J JI Emerg. Med. J. PD OCT PY 2012 VL 29 IS 10 BP 822 EP 825 DI 10.1136/emermed-2011-200584 PG 4 WC Emergency Medicine SC Emergency Medicine GA 020OC UT WOS:000309820200010 PM 22019981 ER PT J AU St-Pierre, J Hivert, MF Perron, P Poirier, P Guay, SP Brisson, D Bouchard, L AF St-Pierre, Julie Hivert, Marie-France Perron, Patrice Poirier, Paul Guay, Simon-Pierre Brisson, Diane Bouchard, Luigi TI IGF2 DNA methylation is a modulator of newborn's fetal growth and development SO EPIGENETICS LA English DT Article DE epigenetics; imprinting; IGF2 and H19; somatomedin A; birth weight; fetal programming ID DEPENDENT DIABETES-MELLITUS; GESTATIONAL-AGE BIRTHS; PRENATAL EXPOSURE; GENE-EXPRESSION; DUTCH FAMINE; WEIGHT; ASSOCIATION; OBESITY; RISK; HYPERTENSION AB The insulin-like growth factor 2 (IGF2) gene, located within a cluster of imprinted genes on chromosome 11p15, encodes a fetal and placental growth factor affecting birth weight. DNA methylation variability at the IGF2 gene locus has been previously reported but its consequences on fetal growth and development are still mostly unknown in normal pediatric population. We collected one hundred placenta biopsies from 50 women with corresponding maternal and cord blood samples and measured anthropometric indices, blood pressure and metabolic phenotypes using standardized procedures. IGF2/H19 DNA methylation and IGF2 circulating levels were assessed using sodium bisulfite pyrosequencing and ELISA, respectively. Placental IGF2 (DMR0 and DMR2) DNA methylation levels were correlated with newborn's fetal growth indices, such as weight, and with maternal IGF2 circulating concentration at the third trimester of pregnancy, whereas H19 (DMR) DNA methylation levels were correlated with IGF2 levels in cord blood. The maternal genotype of a known IGF2/H19 polymorphism (rs2107425) was associated with birth weight. Taken together, we showed that IGF2/H19 epigenotype and genotypes independently account for 31% of the newborn's weight variance. No association was observed with maternal diabetic status, glucose concentrations or prenatal maternal body mass index. This is the first study showing that DNA methylation at the IGF2/H19 genes locus may act as a modulator of IGF2 newborn's fetal growth and development within normal range. IGF2/H19 DNA methylation could represent a cornerstone in linking birth weight and fetal metabolic programming of late onset obesity. C1 [Perron, Patrice; Guay, Simon-Pierre; Brisson, Diane; Bouchard, Luigi] Chicoutimi Hosp, ECOGENE & Lipid Clin 21, Saguenay, PQ, Canada. [St-Pierre, Julie] Chicoutimi Hosp, Dept Pediat, Chicoutimi, PQ, Canada. [Hivert, Marie-France; Perron, Patrice] Univ Sherbrooke, Dept Med, Sherbrooke, PQ J1K 2R1, Canada. [Hivert, Marie-France] Massachusetts Gen Hosp, Gen Med Div, Boston, MA 02114 USA. [Poirier, Paul] Univ Laval, Fac Pharm, Quebec City, PQ, Canada. [Poirier, Paul] Quebec Heart & Lungs Inst, Quebec City, PQ, Canada. [Guay, Simon-Pierre; Bouchard, Luigi] Univ Sherbrooke, Dept Biochem, Sherbrooke, PQ J1K 2R1, Canada. [Brisson, Diane] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. RP Bouchard, L (reprint author), Chicoutimi Hosp, ECOGENE & Lipid Clin 21, Saguenay, PQ, Canada. EM luigi.bouchard@usherbrooke.ca OI Guay, Simon-Pierre/0000-0001-6327-7048 FU ECOGENE-21; Canadian Institutes of Health Research [CTP-82941]; Fonds de la Recherche en Sante du Quebec (FRSQ); Diabete Quebec; CIHR; Canadian Diabetes Association clinical scientist award; FRSQ FX We warmly acknowledge the contribution of Sebastien Claveau (MSc), Nadia Mior, Jeannine Landry (RN) and Chantale Aubut (RN) for their dedicated work in this study. We also express our gratitude to Celine Belanger, Chicoutimi Hospital, for their thoughtful revision of the manuscript. This project was supported by ECOGENE-21, the Canadian Institutes of Health Research (CIHR team in community genetics (grant #CTP-82941), Fonds de la Recherche en Sante du Quebec (FRSQ) and Diabete Quebec. S.P.G. was recipient of a doctoral research award (Frederick Banting and Charles Best Canada Graduate Scholarship) from the CIHR. L.B. and M.F.H. are junior research scholars from the FRSQ. P. Poirier is a senior clinician-scientist of the FRSQ. M.F.H. is also supported by a Canadian Diabetes Association clinical scientist award. L.B. and M.F.H. are members of the FRSQ-funded Centre de recherche clinique Etienne-Le Bel. NR 33 TC 37 Z9 40 U1 3 U2 11 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1559-2294 J9 EPIGENETICS-US JI Epigenetics PD OCT PY 2012 VL 7 IS 10 BP 1125 EP 1132 DI 10.4161/epi.21855 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 022LJ UT WOS:000309960600005 PM 22907587 ER PT J AU Prati, F Guagliumi, G Mintz, GS Costa, M Regar, E Akasaka, T Barlis, P Tearney, GJ Jang, IK Arbustini, E Bezerra, HG Ozaki, Y Bruining, N Dudek, D Radu, M Erglis, A Motreff, P Alfonso, F Toutouzas, K Gonzalo, N Tamburino, C Adriaenssens, T Pinto, F Serruys, PWJ Di Mario, C AF Prati, Francesco Guagliumi, Giulio Mintz, Gary S. Costa, Marco Regar, Evelyn Akasaka, Takashi Barlis, Peter Tearney, Guillermo J. Jang, Ik-Kyung Arbustini, Elosia Bezerra, Hiram G. Ozaki, Yukio Bruining, Nico Dudek, Darius Radu, Maria Erglis, Andrejs Motreff, Pascale Alfonso, Fernando Toutouzas, Kostas Gonzalo, Nieves Tamburino, Corrado Adriaenssens, Tom Pinto, Fausto Serruys, Patrick W. J. Di Mario, Carlo CA Experts OCT Review Document TI Expert review document part 2: methodology, terminology and clinical applications of optical coherence tomography for the assessment of interventional procedures SO EUROPEAN HEART JOURNAL LA English DT Article ID DRUG-ELUTING STENTS; PERCUTANEOUS CORONARY INTERVENTION; INTRAVASCULAR ULTRASOUND GUIDANCE; ELEVATION MYOCARDIAL-INFARCTION; ATHEROSCLEROTIC PLAQUES; NEOINTIMAL COVERAGE; VASCULAR-RESPONSE; STRUT APPOSITION; LUMEN DIMENSIONS; NATURAL-HISTORY C1 [Prati, Francesco] San Giovanni Hosp, Rome, Italy. [Prati, Francesco] CLI Fdn, Rome, Italy. [Guagliumi, Giulio] Osped Riuniti Bergamo, I-24100 Bergamo, Italy. [Mintz, Gary S.] Cardiovasc Res Fdn, New York, NY USA. [Costa, Marco; Bezerra, Hiram G.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Regar, Evelyn; Bruining, Nico; Radu, Maria; Serruys, Patrick W. J.] Univ Rotterdam Hosp, Thoraxctr, Rotterdam, Netherlands. [Regar, Evelyn; Bruining, Nico; Radu, Maria; Serruys, Patrick W. J.] Copenhagen Univ Hosp, Rigshosp, Copenhagen, Denmark. [Akasaka, Takashi] Wakayama Med Univ, Wakayama, Japan. [Barlis, Peter] Univ Melbourne, Northern Hosp, Melbourne, Vic, Australia. [Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tearney, Guillermo J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Arbustini, Elosia] Policlin San Matteo, IRCCS Fdn, I-27100 Pavia, Italy. [Ozaki, Yukio] Fujita Hlth Univ, Toyoake, Aichi, Japan. [Dudek, Darius] Jagiellonian Univ, Inst Cardiol, Univ Hosp, Coll Med, Krakow, Poland. [Erglis, Andrejs] Pauls Stradins Clin Univ Hosp, Riga, Latvia. [Alfonso, Fernando] San Carlos Univ Hosp, Cardiovasc Inst, Madrid, Spain. [Toutouzas, Kostas] Univ Athens, Athens Med Sch, Hippocrat Hosp, Surg Intens Care Unit,Dept Propaedeut Surg 1, Athens, Greece. [Gonzalo, Nieves] Hosp Clin Univ San Carlos, Madrid, Spain. [Tamburino, Corrado] Univ Catania, Dept Cardiol, Catania, Italy. [Adriaenssens, Tom] Univ Hosp Gasthuisberg, Dept Cardiol, B-3000 Louvain, Belgium. [Pinto, Fausto] Univ Lisbon, P-1699 Lisbon, Portugal. [Di Mario, Carlo] Royal Brompton Hosp, London SW3 6LY, England. [Di Mario, Carlo] Univ London Imperial Coll Sci Technol & Med, London, England. RP Prati, F (reprint author), San Giovanni Hosp, Rome, Italy. EM fprati@hsangiovanni.roma.it RI Pinto, Fausto/G-9363-2015; OI Pinto, Fausto/0000-0002-8034-4529; Arbustini, Eloisa/0000-0003-2948-7994; TAMBURINO, Corrado/0000-0002-4940-9742 FU CLI Foundation; St Jude Medical; Boston Scientific; Volcano; Cordis; Medtronic Vascular; Abbott; LightLab Imaging; Biosense Webster; Samsung; Merck; Terumo; Adamed; AstraZeneca; Biotronik; Balton; Bayer; BBraun; BioMatrix; Boehringer Ing; Bristol Myers Squibb; Cook; Eli-Lilly; EuroCor; Glaxo; Invatec; Medtronic; Medicines Company; Nycomed; Orbus-Neich; Pfizer; Possis; Promed; sanofi-aventis; Siemens; Solvay; Stentys; Tyco FX Funding to pay the Open Access publication charges for this article was provided by CLI Foundation.; F.P. has received consultant fees from St Jude Medical. G. G. has received consultant fees from Boston Scientific, St Jude Medical, Volcano, and Cordis; and research grants from Boston Scientific, Medtronic Vascular, Abbott, and LightLab Imaging. G. S. M. has received consultant fees from Volcano and St Jude Medical; and grant support from Volcano and Boston Scientific. M. C. has received consultant fees from Abbott, St Jude Medical, LightLab Imaging, and Biosense Webster; and is a scientific advisor for Scitech. G.J.T. has received consultant fees from Samsung and Merck; royalties from Terumo and MIT; and has received sponsored research from Terumo. I.K.J. has received consultant fees and research grant from St Jude Medical. H. G. B. has received consultant fees and honoraria from St Jude Medical. D. D. has received consultant fees and research grants from Abbott, Adamed, AstraZeneca, Biotronik, Balton, Bayer, BBraun, BioMatrix, Boston Scientific, Boehringer Ing, Bristol Myers Squibb, Cordis, Cook, Eli-Lilly, EuroCor, Glaxo, Invatec, Medtronic, Medicines Company, Merck, Nycomed, Orbus-Neich, Pfizer, Possis, Promed, sanofi-aventis, Siemens, Solvay, Stentys, Terumo, and Tyco; and is an advisory board member. P. M. has received consultant fees from St Jude Medical and Terumo. T. A. has received consultant fees and carried out educational activity for St Jude Medical. C. D. M. has received speaker fees from St Jude Medical. NR 57 TC 107 Z9 107 U1 1 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD OCT PY 2012 VL 33 IS 20 BP 2513 EP + DI 10.1093/eurheartj/ehs095 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 025EC UT WOS:000310167200008 PM 22653335 ER PT J AU Guinan, JJ AF Guinan, John J., Jr. TI How are inner hair cells stimulated? Evidence for multiple mechanical drives SO HEARING RESEARCH LA English DT Article ID AUDITORY-NERVE RESPONSES; OLIVOCOCHLEAR-EFFERENT INHIBITION; BASILAR-MEMBRANE RESPONSES; CHRONIC COCHLEAR PATHOLOGY; LOW-FREQUENCY TONES; TECTORIAL MEMBRANE; ELECTRICAL-STIMULATION; HYDRODYNAMIC-FORCES; STEREOCILIA DAMAGE; CHINCHILLA COCHLEA AB Recent studies indicate that the gap over outer hair cells (OHCs) between the reticular lamina (RL) and the tectorial membrane (TM) varies cyclically during low-frequency sounds. Variation in the RL-TM gap produces radial fluid flow in the gap that can drive inner hair cell (IHC) stereocilia. Analysis of RL-TM gap changes reveals three IHC drives in addition to classic SHEAR. For upward basilar-membrane (BM) motion, IHC stereocilia are deflected in the excitatory direction by SHEAR and OHC-MOTILITY, but in the inhibitory direction by TM-PUSH and CILIA-SLANT. Upward BM motion causes OHC somatic contraction which tilts the RL, compresses the RL-TM gap over IHCs and expands the RL-TM gap over OHCs, thereby producing an outward (away from the IHCs) radial fluid flow which is the OHC-MOTILITY drive. For upward BM motion, the force that moves the TM upward also compresses the RL-TM gap over OHCs causing inward radial flow past IHCs which is the TM-PUSH drive. Motions that produce large tilting of OHC stereocilia squeeze the supra-OHC RL-TM gap and caused inward radial flow past IHCs which is the CILIA-SLANT drive. Combinations of these drives explain: (1) the reversal at high sound levels of auditory nerve (AN) initial peak (ANIP) responses to clicks, and medial olivocochlear (MOC) inhibition of ANIP responses below, but not above, the ANIP reversal, (2) dips and phase reversals in AN responses to tones in cats and chinchillas, (3) hypersensitivity and phase reversals in tuning-curve tails after OHC ablation, and (4) MOC inhibition of tail-frequency AN responses. The OHC-MOTILITY drive provides another mechanism, in addition to BM motion amplification, that uses active processes to enhance the output of the cochlea. The ability of these IHC drives to explain previously anomalous data provides strong, although indirect, evidence that these drives are significant and presents a new view of how the cochlea works at frequencies below 3 kHz. (c) 2012 Elsevier B.V. All rights reserved. C1 [Guinan, John J., Jr.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. [Guinan, John J., Jr.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Guinan, John J., Jr.] Harvard MIT Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. RP Guinan, JJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. EM jjg@epl.meei.harvard.edu FU NIH NIDCD [RO1 DC000235, P30 DC005209] FX I thank Dr. Dennis Freedman and Dr. Christopher Shera for comments on an earlier version of the manuscript. Supported by NIH NIDCD RO1 DC000235 and P30 DC005209. NR 81 TC 25 Z9 25 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 EI 1878-5891 J9 HEARING RES JI Hear. Res. PD OCT PY 2012 VL 292 IS 1-2 BP 35 EP 50 DI 10.1016/j.heares.2012.08.005 PG 16 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 024GJ UT WOS:000310097400004 PM 22959529 ER PT J AU Stefanija, MA Jeanpierre, M Sykiotis, GP Young, J Quinton, R Abreu, AP Plummer, L Au, MG Balasubramanian, R Dwyer, AA Florez, JC Cheetham, T Pearce, SH Purushothaman, R Schinzel, A Pugeat, M Jacobson-Dickman, EE Ten, S Latronico, AC Gusella, JF Dode, C Crowley, WF Pitteloud, N AF Stefanija, Magdalena Avbelj Jeanpierre, Marc Sykiotis, Gerasimos P. Young, Jacques Quinton, Richard Abreu, Ana Paula Plummer, Lacey Au, Margaret G. Balasubramanian, Ravikumar Dwyer, Andrew A. Florez, Jose C. Cheetham, Timothy Pearce, Simon H. Purushothaman, Radhika Schinzel, Albert Pugeat, Michel Jacobson-Dickman, Elka E. Ten, Svetlana Latronico, Ana Claudia Gusella, James F. Dode, Catherine Crowley, William F., Jr. Pitteloud, Nelly TI An ancient founder mutation in PROKR2 impairs human reproduction SO HUMAN MOLECULAR GENETICS LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; OF-FUNCTION MUTATIONS; KALLMANN-SYNDROME; RECEPTOR GENE; CYSTIC-FIBROSIS; PROKINETICIN 2; OLFACTORY-BULB; DEFICIENCY; MICE AB Congenital gonadotropin-releasing hormone (GnRH) deficiency manifests as absent or incomplete sexual maturation and infertility. Although the disease exhibits marked locus and allelic heterogeneity, with the causal mutations being both rare and private, one causal mutation in the prokineticin receptor, PROKR2 L173R, appears unusually prevalent among GnRH-deficient patients of diverse geographic and ethnic origins. To track the genetic ancestry of PROKR2 L173R, haplotype mapping was performed in 22 unrelated patients with GnRH deficiency carrying L173R and their 30 first-degree relatives. The mutations age was estimated using a haplotype-decay model. Thirteen subjects were informative and in all of them the mutation was present on the same approximate to 123 kb haplotype whose population frequency is 10. Thus, PROKR2 L173R represents a founder mutation whose age is estimated at approximately 9000 years. Inheritance of PROKR2 L173R-associated GnRH deficiency was complex with highly variable penetrance among carriers, influenced by additional mutations in the other PROKR2 allele (recessive inheritance) or another gene (digenicity). The paradoxical identification of an ancient founder mutation that impairs reproduction has intriguing implications for the inheritance mechanisms of PROKR2 L173R-associated GnRH deficiency and for the relevant processes of evolutionary selection, including potential selective advantages of mutation carriers in genes affecting reproduction. C1 [Dwyer, Andrew A.; Pitteloud, Nelly] CHU Vaudois, Endocrine Diabet & Metab Serv, CH-1011 Lausanne, Switzerland. [Stefanija, Magdalena Avbelj; Plummer, Lacey; Au, Margaret G.; Balasubramanian, Ravikumar; Crowley, William F., Jr.] Massachusetts Gen Hosp, Harvard Reprod Endocrine Sci Ctr, Boston, MA 02114 USA. [Stefanija, Magdalena Avbelj; Plummer, Lacey; Au, Margaret G.; Balasubramanian, Ravikumar; Crowley, William F., Jr.] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Ctr Human Genet Res, Boston, MA 02114 USA. [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA. [Stefanija, Magdalena Avbelj] Univ Med Ctr Ljubljana, Univ Childrens Hosp, Dept Pediat Endocrinol Diabet & Metab, Ljubljana 1000, Slovenia. [Jeanpierre, Marc; Dode, Catherine] Univ Paris 05, Inst Cochin, INSERM, U1016, F-75014 Paris, France. [Sykiotis, Gerasimos P.] Univ Patras, Sch Med, Dept Internal Med, Div Endocrinol, Patras 26500, Greece. [Sykiotis, Gerasimos P.] Univ Patras, Sch Med, Dept Pharmacol, Patras 26500, Greece. [Young, Jacques] Univ Paris 11, Fac Med Paris S, F-94276 Le Kremlin Bicetre, France. [Young, Jacques] INSERM, U693, F-94276 Le Kremlin Bicetre, France. [Quinton, Richard; Cheetham, Timothy; Pearce, Simon H.] Newcastle Univ, Inst Human Genet, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England. [Quinton, Richard] Newcastle Upon Tyne Hosp, Dept Endocrinol, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Cheetham, Timothy] Newcastle Upon Tyne Hosp, Dept Paediat, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. [Abreu, Ana Paula; Latronico, Ana Claudia] Univ Sao Paulo, Lab Hormonios & Genet Mol, Unidade Endocrinol Desenvolvimento, Hosp Clin,Fac Med,LIM 42, BR-05403900 Sao Paulo, Brazil. [Florez, Jose C.; Gusella, James F.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Florez, Jose C.; Crowley, William F., Jr.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Gusella, James F.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Purushothaman, Radhika; Jacobson-Dickman, Elka E.; Ten, Svetlana] Suny Downstate Med Ctr, Div Pediat Endocrinol, Brooklyn, NY 11219 USA. [Purushothaman, Radhika; Jacobson-Dickman, Elka E.; Ten, Svetlana] Maimonides Infants & Childrens Hosp Brooklyn, Div Pediat Endocrinol, Brooklyn, NY 11219 USA. [Schinzel, Albert] Univ Zurich, Inst Med Genet, CH-8603 Schwerzenbach, Switzerland. [Pugeat, Michel] Univ Lyon 1, INSERM, U1060, F-69677 Bron, France. [Pugeat, Michel] Hosp Civils Lyon, F-69677 Bron, France. RP Pitteloud, N (reprint author), CHU Vaudois, Endocrine Diabet & Metab Serv, Rue Bugnon 46,BH 19-701, CH-1011 Lausanne, Switzerland. EM nelly.pitteloud@chuv.ch RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014; OI Pearce, Simon/0000-0001-8384-8063; Dwyer, Andrew/0000-0002-7023-6794; Avbelj Stefanija, Magdalena/0000-0002-0836-5114; Sykiotis, Gerasimos/0000-0002-9565-4941; Latronico Xavier, Ana Claudia/0000-0001-6782-693X FU National Institutes of Health [U54 HD028138, R01 HD015788, R01 HD056264, P01 GM061354]; Agence Nationale de la Recherche [ANR-09-GENO-017]; Slovene National Research Agency [P3-0343] FX This work was supported by the National Institutes of Health (U54 HD028138 and R01 HD015788 to W.F.C., R01 HD056264 to N.P., P01 GM061354 to J.F.G.); the Agence Nationale de la Recherche (ANR-09-GENO-017 to C.D.); and the Slovene National Research Agency (P3-0343 to M.A.S.). NR 62 TC 5 Z9 5 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 1 PY 2012 VL 21 IS 19 BP 4314 EP 4324 DI 10.1093/hmg/dds264 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 007KV UT WOS:000308888100014 ER PT J AU McLaren, PJ Ripke, S Pelak, K Weintrob, AC Patsopoulos, NA Jia, XM Erlich, RL Lennon, NJ Kadie, CM Heckerman, D Gupta, N Haas, DW Deeks, SG Pereyra, F Walker, BD de Bakker, PIW AF McLaren, Paul J. Ripke, Stephan Pelak, Kimberly Weintrob, Amy C. Patsopoulos, Nikolaos A. Jia, Xiaoming Erlich, Rachel L. Lennon, Niall J. Kadie, Carl M. Heckerman, David Gupta, Namrata Haas, David W. Deeks, Steven G. Pereyra, Florencia Walker, Bruce D. de Bakker, Paul I. W. CA Int HIV Controllers Study TI Fine-mapping classical HLA variation associated with durable host control of HIV-1 infection in African Americans SO HUMAN MOLECULAR GENETICS LA English DT Article ID WHOLE-GENOME ASSOCIATION; CLASS-I; WIDE ASSOCIATION; EXPRESSION; COMPLEX; AIDS; DETERMINANTS; PROGRESSION; ALLELES; GENE AB A small proportion of human immunodeficiency virus-1 (HIV-1) infected individuals, termed HIV-1 controllers, suppress viral replication to very low levels in the absence of therapy. Genetic investigations of this phenotype have strongly implicated variation in the class I major histocompatibility complex (MHC) region as key to HIV-1 control. We collected sequence-based classical class I HLA genotypes at 4-digit resolution in HIV-1-infected African American controllers and progressors (n 1107), and tested them for association with host control using genome-wide single nucleotide polymorphism data to account for population structure. Several classical alleles at HLA-B were associated with host control, including B57:03 [odds ratio (OR) 5.1; P 3.4 10(18)] and B81:01 (OR 4.8; P 1.3 10(9)). Analysis of variable amino acid positions demonstrates that HLA-B position 97 is the most significant association with host control in African Americans (omnibus P 1.2 10(21)) and explains the signal of several HLA-B alleles, including B57:03. Within HLA-B, we also identified independent effects at position 116 (omnibus P 2.8 10(15)) in the canonical F pocket, position 63 in the B pocket (P 1.5 10(3)) and the non-pocket position 245 (P 8.8 10(10)), which is thought to influence CD8-binding kinetics. Adjusting for these HLA-B effects, there is evidence for residual association in the MHC region. These results underscore the key role of HLA-B in affecting HIV-1 replication, likely through the molecular interaction between HLA-B and viral peptides presented by infected cells, and suggest that sites outside the peptide-binding pocket also influence HIV-1 control. C1 [McLaren, Paul J.; Patsopoulos, Nikolaos A.; de Bakker, Paul I. W.] Harvard Univ, Div Genet, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Pereyra, Florencia] Harvard Univ, Div Infect Dis, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Patsopoulos, Nikolaos A.; de Bakker, Paul I. W.] Harvard Univ, Dept Neurol, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [McLaren, Paul J.; Ripke, Stephan; Patsopoulos, Nikolaos A.; Erlich, Rachel L.; Lennon, Niall J.; Gupta, Namrata] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Ripke, Stephan] Harvard Univ, Ctr Human Genet Res, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Pelak, Kimberly] Duke Univ, Sch Med, Ctr Human Genome Variat, Durham, NC USA. [Weintrob, Amy C.] Uniformed Serv Univ Hlth Sci, Infect Dis Clin Res Program, Bethesda, MD 20814 USA. [Jia, Xiaoming] Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. [Heckerman, David] Microsoft Res, Los Angeles, CA USA. [Kadie, Carl M.] Microsoft Res, Redmond, WA USA. [Haas, David W.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Deeks, Steven G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Epidemiol, Utrecht, Netherlands. [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [Pereyra, Florencia; Walker, Bruce D.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Charlestown, MA USA. RP de Bakker, PIW (reprint author), Harvard Univ, Div Genet, Sch Med, Brigham & Womens Hosp, 77 Ave Louis Pasteur,New Res Bldg,Suite 168, Boston, MA 02115 USA. EM pdebakker@rics.bwh.harvard.edu RI de Bakker, Paul/B-8730-2009; Marconi, Vincent/N-3210-2014 OI de Bakker, Paul/0000-0001-7735-7858; Marconi, Vincent/0000-0001-8409-4689 FU Collaboration for AIDS Vaccine Discovery (CAVD) of the Bill and Melinda Gates Foundation; Harvard University Center for AIDS Research [P-30-AI060354]; UCSF CFAR [P-30 AI27763]; UCSF CTSI [UL1 RR024131]; CNICS [R24 AI067039]; Vanderbilt CTSA [RR024975]; NIH [AI28568, AI030914, AI087145, K24AI069994, AI069513, AI34835, AI069432, AI069423, AI069477, AI069501, AI069474, AI069428, AI69467]; Infectious Disease Clinical Research Program (IDCRP); Department of Defense (DoD) through the Uniformed Services University of the Health Sciences; National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), under Inter-Agency Agreement [Y1-AI-5072]; The NIH [RR024975, AI069415, Al32782, AI27661, AI25859, AI30914, AI069495, AI069471, AI069532, AI069452, AI069450, AI069556, AI069484, AI069472, AI34853, AI069465, AI069511, AI38844, AI069424, AI069434, AI46370, AI68634, AI069502, AI069419, AI068636, AI077505, MH071205] FX This work was made possible through a generous donation from the Mark and Lisa Schwartz Foundation and a subsequent award from the Collaboration for AIDS Vaccine Discovery (CAVD) of the Bill and Melinda Gates Foundation. This work was also supported in part by the Harvard University Center for AIDS Research (P-30-AI060354), UCSF CFAR (P-30 AI27763), UCSF CTSI (UL1 RR024131), CNICS (R24 AI067039), Vanderbilt CTSA (RR024975), NIH grants AI28568, AI030914 (B.D.W.); AI087145, K24AI069994 (S.G.D.); AI069513, AI34835, AI069432, AI069423, AI069477, AI069501, AI069474, AI069428, AI69467, AI069415, Al32782, AI27661, AI25859, AI28568, AI30914, AI069495, AI069471, AI069532, AI069452, AI069450, AI069556, AI069484, AI069472, AI34853, AI069465, AI069511, AI38844, AI069424, AI069434, AI46370, AI68634, AI069502, AI069419, AI068636, RR024975 (AIDS Clinical Trials Group); AI077505 and MH071205 (D.W.H.). S.R. acknowledges support from NIH/NIMH (MH085520).; Additional support for this work was provided by the Infectious Disease Clinical Research Program (IDCRP), a Department of Defense (DoD) program executed through the Uniformed Services University of the Health Sciences. This project has been funded in whole, or in part, with federal funds from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), under Inter-Agency Agreement Y1-AI-5072. NR 46 TC 28 Z9 29 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 1 PY 2012 VL 21 IS 19 BP 4334 EP 4347 DI 10.1093/hmg/dds226 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 007KV UT WOS:000308888100016 PM 22718199 ER PT J AU Soreide, K Ogino, S AF Soreide, Kjetil Ogino, Shuji TI Microsatellite instability and retrieval of lymph nodes in stage III colon cancer: harbinger or hermit? SO HUMAN PATHOLOGY LA English DT Letter C1 [Soreide, Kjetil] Univ Bergen, Dept Surg Sci, Bergen, Norway. [Soreide, Kjetil] Stavanger Univ Hosp, Dept Surg, GI Unit, N-4068 Stavanger, Norway. [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. [Ogino, Shuji] Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02215 USA. RP Soreide, K (reprint author), Univ Bergen, Dept Surg Sci, Bergen, Norway. EM ksoreide@mac.com OI Soreide, Kjetil/0000-0001-7594-4354 NR 6 TC 1 Z9 1 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD OCT PY 2012 VL 43 IS 10 BP 1785 EP 1786 DI 10.1016/j.humpath.2012.05.025 PG 2 WC Pathology SC Pathology GA 018VC UT WOS:000309693600033 PM 22835957 ER PT J AU Kim, SJ Lee, H Kato, K Yonetsu, T Xing, L Zhang, SS AF Kim, Soo-Joong Lee, Hang Kato, Koji Yonetsu, Taishi Xing, Lei Zhang, Shaosong TI Reproducibility of In Vivo Measurements for Fibrous Cap Thickness and Lipid Arc by OCT SO JACC-CARDIOVASCULAR IMAGING LA English DT Letter ID OPTICAL COHERENCE TOMOGRAPHY; PLAQUE C1 [Kim, Soo-Joong; Lee, Hang; Kato, Koji; Yonetsu, Taishi; Xing, Lei; Zhang, Shaosong] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Kim, SJ (reprint author), Massachusetts Gen Hosp, Div Cardiol, GRB 800,55 Fruit St, Boston, MA 02114 USA. EM ijang@partners.org NR 3 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD OCT PY 2012 VL 5 IS 10 BP 1072 EP 1074 DI 10.1016/j.jcmg.2012.04.011 PG 4 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 023XB UT WOS:000310069600015 PM 23058077 ER PT J AU Chen, J Fang, QQ Intes, X AF Chen, Jin Fang, Qianqian Intes, Xavier TI Mesh-based Monte Carlo method in time-domain widefield fluorescence molecular tomography SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE fluorescence; infrared imaging; multispectral imaging; photonics; tomography ID SMALL ANIMALS; OPTICAL TOMOGRAPHY; PHOTON MIGRATION; IN-VIVO; MEDIA; SIMULATION; LIGHT; RECONSTRUCTION; APPROXIMATION; ILLUMINATION AB We evaluated the potential of mesh-based Monte Carlo (MC) method for widefield time-gated fluorescence molecular tomography, aiming to improve accuracy in both shape discretization and photon transport modeling in preclinical settings. An optimized software platform was developed utilizing multithreading and distributed parallel computing to achieve efficient calculation. We validated the proposed algorithm and software by both simulations and in vivo studies. The results establish that the optimized mesh-based Monte Carlo (mMC) method is a computationally efficient solution for optical tomography studies in terms of both calculation time and memory utilization. The open source code, as part of a new release of mMC, is publicly available at http://mcx.sourceforge.net/mmc/. (C) 2012 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.JBO.17.10.106009] C1 [Chen, Jin; Intes, Xavier] Rensselaer Polytech Inst, Dept Biomed Engn, Troy, NY 12180 USA. [Fang, Qianqian] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Intes, X (reprint author), Rensselaer Polytech Inst, Dept Biomed Engn, Troy, NY 12180 USA. EM intesx@rpi.edu FU National Institutes of Health (NIH) [R21 EB013421]; National Science Foundation (NSF) [CBET-1149407]; Bill & Melinda Gates Foundation [OPP1035992] FX This work was supported by National Institutes of Health (NIH) grant R21 EB013421 and by the National Science Foundation (NSF) grant CBET-1149407. Qianqian Fang wishes to thank the funding support from the Bill & Melinda Gates Foundation (#OPP1035992). NR 35 TC 20 Z9 20 U1 0 U2 23 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD OCT PY 2012 VL 17 IS 10 AR 106009 DI 10.1117/1.JBO.17.10.106009 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 021UK UT WOS:000309910700036 PM 23224008 ER PT J AU Gioux, S Coutard, JG Berger, M Grateau, H Josserand, V Keramidas, M Righini, C Coll, JL Dinten, JM AF Gioux, Sylvain Coutard, Jean-Guillaume Berger, Michel Grateau, Henri Josserand, Veronique Keramidas, Michelle Righini, Christian Coll, Jean-Luc Dinten, Jean-Marc TI FluoSTIC: miniaturized fluorescence image-guided surgery system SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE clinical translation; near-infrared fluorescence; image-guided surgery ID NEAR-INFRARED FLUORESCENCE; ARTERY-BYPASS GRAFT; CANCER PATIENTS; VISUALIZATION; DEVICE; CAMERA; TISSUE AB Over the last few years, near-infrared (NIR) fluorescence imaging has witnessed rapid growth and is already used in clinical trials for various procedures. However, most clinically compatible imaging systems are optimized for large, open-surgery procedures. Such systems cannot be employed during head and neck oncologic surgeries because the system is not able to image inside deep cavities or allow the surgeon access to certain tumors due to the large footprint of the system. We describe a miniaturized, low-cost, NIR fluorescence system optimized for clinical use during oral oncologic surgeries. The system, termed FluoSTIC, employs a miniature, high-quality, consumer-grade lipstick camera for collecting fluorescence light and a novel custom circular optical fiber array for illumination that combines both white light and NIR excitation. FluoSTIC maintains fluorescence imaging quality similar to that of current large-size imaging systems and is 22 mm in diameter and 200 mm in height and weighs less than 200 g. (C) 2012 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.JBO.17.10.106014] C1 [Gioux, Sylvain] Harvard Univ, Sch Med, BIDMC, Boston, MA 02215 USA. [Gioux, Sylvain; Coutard, Jean-Guillaume; Berger, Michel; Grateau, Henri; Dinten, Jean-Marc] CEA LETI, Minatec, F-38054 Grenoble, France. [Josserand, Veronique; Keramidas, Michelle; Righini, Christian; Coll, Jean-Luc] Univ Grenoble 1, Inst Albert Bonniot, F-38706 Grenoble, France. [Righini, Christian] Univ Hosp Grenoble, Head & Neck Surg Dept, F-38706 Grenoble, France. [Righini, Christian] Univ Grenoble 1, Fac Med Grenoble, F-38041 Grenoble, France. RP Gioux, S (reprint author), Harvard Univ, Sch Med, BIDMC, Room SLB 05,330 Brookline Ave, Boston, MA 02215 USA. EM sgioux@bidmc.harvard.edu RI josserand, veronique/M-2767-2013; Coll, Jean-Luc/G-2520-2013 OI Coll, Jean-Luc/0000-0002-2453-3552 FU Contrat Plan Etat Region (CPER, France) FX The authors thank Veronique Birkenheier for administrative assistance and Lindsey Gendall and David Burrington, Jr., for editing. The authors thank the following individuals for their contributions to the project: from CEA-LETI, Cedric Allier, Anne Planat-Chretien, and Vincent Poher; from Fluoptics, Philippe Rizo and Norman Mangeret; from Chroma, Kelly Stock-well; from Fiber Tech Optica, Jeff Dupuis and Rafal Pawluczyk. This study was funded by a Contrat Plan Etat Region (CPER, France). NR 29 TC 17 Z9 17 U1 0 U2 15 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD OCT PY 2012 VL 17 IS 10 AR 106014 DI 10.1117/1.JBO.17.10.106014 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 021UK UT WOS:000309910700041 PM 23052561 ER PT J AU Boehmer, JP Starling, RC Cooper, LT Torre-Amione, G Wittstein, I Dec, GW Markham, DW Zucker, MJ Gorcsan, J McTiernan, C Kip, K McNamara, DM AF Boehmer, John P. Starling, Randall C. Cooper, Leslie T. Torre-Amione, Guillermo Wittstein, Ilan Dec, G. William Markham, David W. Zucker, Mark J. Gorcsan, John, III McTiernan, Charles Kip, Kevin McNamara, Dennis M. CA IMAC Investigators TI Left Ventricular Assist Device Support and Myocardial Recovery in Recent Onset Cardiomyopathy SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Mechanical circulatory support (MCS); myocarditis; nonischemic cardiomyopathy; outcomes ID MECHANICAL CIRCULATORY SUPPORT; HEART-FAILURE; CONTINUOUS-FLOW; DILATED CARDIOMYOPATHY; EXPRESSION; IMPROVEMENT; PULSATILE AB Background: Left ventricular assist device (LVAD) support as bridge to recovery (BTR) is uncommon for subjects with chronic heart failure. Myocardial recovery is more evident in recent onset nonischemic cardiomyopathy (ROCM); however, the prevalence of BTR in this subset has not been addressed. Methods and Results: We examined the use of LVAD support for subjects with ROCM in the Intervention in Myocarditis and Acute Cardiomyopathy 2 (IMAC2) study. The overall cohort (n = 373) was 38% female, 21% black, with a mean age of 45 +/- 14 years. LVAD support was used in 3.8% (n = 14, 43% female, age 32 +/- 10). Of LVAD subjects, 57% (8/14) were BTR, including 73% (8/11) of subjects with symptoms <= 4 months at the time of support. Left ventricular end-diastolic diameter (LVEDD) was smaller in BTR than nonrecovered (NR) subjects (P = .04). Myocardial inflammation was more common in BTR (75% versus 0%, P = .005), whereas fibrosis was less evident (25% versus 100%, P = .005). Of BTR subjects, 7/8 (87.5%) were alive and free of transplant with median follow-up of 19 months. Conclusion: In a multicenter registry of ROCM, BTR was common and occurred in the majority of subjects requiring LVAD support. Histology and LVEDD may assist in predicting potential for BTR in ROCM. (J Cardiac Fail 2012;18:755-761) C1 [Gorcsan, John, III; McTiernan, Charles; McNamara, Dennis M.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. [Boehmer, John P.] Penn State Univ, Coll Med, Hershey, PA USA. [Starling, Randall C.] Cleveland Clin, Cleveland, OH 44106 USA. [Cooper, Leslie T.] Mayo Clin, Rochester, MN USA. [Torre-Amione, Guillermo] Methodist Hosp, Houston, TX 77030 USA. [Wittstein, Ilan] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Dec, G. William] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Markham, David W.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Zucker, Mark J.] Newark Beth Israel Med Ctr, Newark, NJ USA. [Kip, Kevin] Univ S Florida, Tampa, FL USA. RP McNamara, DM (reprint author), Univ Pittsburgh, Med Ctr, 566 Scaife Hall,200 Lothrop St, Pittsburgh, PA 15213 USA. EM mcnamaradm@upmc.edu FU NHLBI [HL075038, HL69912] FX Investigation supported by NHLBI contracts HL075038 and HL69912. NR 27 TC 21 Z9 21 U1 0 U2 3 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD OCT PY 2012 VL 18 IS 10 BP 755 EP 761 DI 10.1016/j.cardfail.2012.08.001 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 025HS UT WOS:000310179900002 PM 23040110 ER PT J AU Goodlin, SJ Wingate, S Albert, NM Pressler, SJ Houser, J Kwon, J Chiong, J Storey, CP Quill, T Teerlink, JR AF Goodlin, Sarah J. Wingate, Sue Albert, Nancy M. Pressler, Susan J. Houser, Janet Kwon, Jennifer Chiong, Jun Storey, C. Porter Quill, Timothy Teerlink, John R. CA PAIN-HF Investigators TI Investigating Pain in Heart Failure Patients: The Pain Assessment, Incidence, and Nature in Heart Failure (PAIN-HF) Study SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Heart failure; pain; symptoms; arthritis shortness of breath; opioids ID DEPRESSION; PREVALENCE; VALIDATION; EXERCISE; QUALITY; LIFE; CARE AB Background: Patients with advanced heart failure (HF) have high rates of pain and other symptoms that diminish quality of life. We know little about the characteristics and correlates of pain in patients with advanced HF. Methods and Results: We identified pain prevalence, location, character, severity, frequency, and correlates in 347 outpatients with advanced HF enrolled from hospices and clinics. We evaluated the correlation of pain with HF-related quality of life, mortality, symptoms and health problems, and current treatments for pain. Pain at any site was reported by 293 patients (84.4%), and 138 (39.5%) reported pain at more than one site. The most common site of pain was the legs below the knees (32.3% of subjects). Pain interfered with activity for 70% of patients. Pain was "severe" or "very severe" for 28.6% of subjects with chest pain, and for 38.9% of those with other sites of pain. The only medication reported to provide pain relief was opioids, prescribed for 34.1% of subjects (P = .001). The strongest predictors of pain were degenerative joint disease (DJD) (odds ratio [OR] 14.95, 95% confidence interval [CI] 3.9-56.0; P < .001), other arthritis (OR 2.8, 95% CI 1.20-6.62; P = .017), shortness of breath (OR 3.27, 95% CI 1.47-7.28; P = .004), and angina pectoris (OR 3.38, 95% CI 1.30-8.81; P = .013). Conclusions: Pain occurred at multiple sites in patients with advanced HF. Pain correlated with DJD or other arthritis, shortness of breath, and angina. Only opioid analgesics provided relief of pain. Future research should evaluate the etiology of and interventions to manage pain in patients with HF. (J Cardiac Fail 2012;18:776-783) C1 [Goodlin, Sarah J.] Patient Ctr Educ & Res, Salt Lake City, UT 84103 USA. [Goodlin, Sarah J.] Portland VA Med Ctr, Portland, OR USA. [Wingate, Sue] Midatlantic States Kaiser Permanente, Silver Spring, MD USA. [Albert, Nancy M.] Cleveland Clin, RN Nursing Inst, Cleveland, OH 44106 USA. [Albert, Nancy M.] Cleveland Clin, Kaufman Ctr Heart Failure, Cleveland, OH 44106 USA. [Pressler, Susan J.] Univ Michigan, Ann Arbor, MI 48109 USA. [Houser, Janet] Regis Univ, Denver, CO USA. [Chiong, Jun] Loma Linda Univ, Med Ctr, Loma Linda, CA 92350 USA. [Storey, C. Porter] Kaiser Permanente, Denver, CO USA. [Quill, Timothy] Univ Rochester, Rochester, NY USA. [Teerlink, John R.] UCSF VAMC San Francisco, San Francisco, CA USA. RP Goodlin, SJ (reprint author), Patient Ctr Educ & Res, Salt Lake City, UT 84103 USA. EM sgoodlin@patient-centered.org FU Mayday Fund, New York, New York FX The Mayday Fund, New York, New York. NR 23 TC 19 Z9 20 U1 0 U2 5 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD OCT PY 2012 VL 18 IS 10 BP 776 EP 783 DI 10.1016/j.cardfail.2012.07.007 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 025HS UT WOS:000310179900005 PM 23040113 ER PT J AU Ramasubbu, K Deswal, A Chan, WY Aguilar, D Bozkurt, B AF Ramasubbu, Kumudha Deswal, Anita Chan, Wenyaw Aguilar, David Bozkurt, Biykem TI Echocardiographic Changes During Treatment of Acute Decompensated Heart Failure: Insights From the ESCAPE Trial SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Heart failure; echocardiography; acute echocardiographic changes; ESCAPE trial ID IDIOPATHIC DILATED CARDIOMYOPATHY; ARTERY CATHETERIZATION EFFECTIVENESS; VENTRICULAR SYSTOLIC DYSFUNCTION; NATRIURETIC PEPTIDE; DOPPLER-ECHOCARDIOGRAPHY; DIASTOLIC PRESSURE; EJECTION FRACTION; SECONDARY; SURVIVAL; EXERCISE AB Background: Long-term heart failure (HF) treatment has been shown to result in reverse chamber remodeling. However, it is unknown whether sizes of cardiac chambers acutely change during HF therapy and whether these changes are associated with favorable clinical outcomes. Methods and Results: Using the Evaluation Study of Congestive Heart Failure and Pulsmonary Artery Catheterization Effectiveness (ESCAPE) trial database, echocardiographic parameters at baseline and discharge, changes from baseline to discharge, and their association with the combined endpoint of death or HF rehospitalization (HFH) at 6 months were evaluated in patients admitted with acute decompensated HF (ADHF). Also, the correlation between changes in invasive hemodynamic parameters compared with changes in echocardiographic parameters was analyzed. During the treatment of ADHF, right atrium, right ventricle, and inferior vena cava (IVC) sizes decreased acutely. Mitral regurgitation severity and mitral inflow parameters also improved significantly. However, the majority of acute changes in echocardiographic parameters did not have an impact on clinical outcome, except for the reduction in left ventricular (LV) end-diastolic and end-systolic volumes, which was associated with a reduction in the combined outcome of HFH or death. The change in invasive hemodynamics that best correlated with change in echocardiographic parameters was change in pulmonary capillary wedge pressure with change in IVC diameter and IVC collapsibility. Conclusions: This is the first study to identify the echocardiographic parameters that change during the treatment of ADHF and the echocardiographic parameters that most reliably correlate with invasive hemodynamic changes. Most changes in echocardiographic parameters were not associated with clinical outcomes, except for the reduction in LV volume, which was associated with a reduction in HFH or death. (J Cardiac Fail 2012;18:792-798) C1 [Ramasubbu, Kumudha; Deswal, Anita; Bozkurt, Biykem] Michael E DeBakey Vet Adm Med Ctr, Dept Cardiol, Baylor Coll Med, Houston, TX USA. [Chan, Wenyaw] Univ Texas Hlth Sci Ctr, Sch Publ Hlth, Houston, TX USA. RP Ramasubbu, K (reprint author), Michael E DeBakey VA Med Ctr, Dept Cardiol 3C 300A, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM kumudhar@bcm.tmc.edu NR 29 TC 10 Z9 10 U1 0 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD OCT PY 2012 VL 18 IS 10 BP 792 EP 798 DI 10.1016/j.cardfail.2012.08.358 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 025HS UT WOS:000310179900007 PM 23040115 ER PT J AU Ulvenes, PG Berggraf, L Hoffart, A Levy, RA Ablon, JS McCullough, L Wampold, BE AF Ulvenes, Pal G. Berggraf, Lene Hoffart, Asle Levy, Raymon A. Ablon, J. Stuart McCullough, Leigh Wampold, Bruce E. TI Can Two Psychotherapy Process Measures Be Dependably Rated Simultaneously? A Generalizability Study SO JOURNAL OF COUNSELING PSYCHOLOGY LA English DT Article DE generalizability; observer ratings; psychotherapy assessment ID TERM DYNAMIC PSYCHOTHERAPY; COGNITIVE THERAPY; OBSERVER RATINGS; RELIABILITY; ACHIEVEMENT; VARIANCE; SESSIONS; PATIENT; BIAS AB Observer ratings in psychotherapy are a common way of collecting information in psychotherapy research. However, human observers are imperfect instruments, and their ratings may be subject to variability from several sources. One source of variability can be raters' assessing more than 1 instrument at a time. The purpose of this research is to investigate whether it is possible to have raters assess 2 different psychotherapy process measures simultaneously and still produce dependable scores. Two studies were designed. The first compared scores assessed by raters who rated either 1 instrument or 2 instruments simultaneously. The second compared scores of raters who assessed 2 instruments simultaneously and scores of expert raters who assessed 1 instrument. The results show that variability in scores is largely due to differences across the object of measurement (e.g., patients). Small variability was reported for raters, raters' interaction with patients, and whether the rater assessed 1 instrument or 2 instruments simultaneously. The results are promising for the quality of observer ratings of psychotherapy process and for the feasibility of future psychotherapy process research. C1 [Ulvenes, Pal G.; Berggraf, Lene; Hoffart, Asle; McCullough, Leigh; Wampold, Bruce E.] Modum Bad Psychiat Ctr, Res Inst, Vikersund, Norway. [Ulvenes, Pal G.; Berggraf, Lene; Hoffart, Asle] Univ Oslo, Dept Psychol, Oslo, Norway. [Levy, Raymon A.; Ablon, J. Stuart] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. [McCullough, Leigh] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Psychiat, Sch Med, Cambridge, MA 02138 USA. [Wampold, Bruce E.] Univ Wisconsin, Dept Counseling Psychol, Madison, WI USA. RP Ulvenes, PG (reprint author), Modum Bad, Forskningsinst, N-3370 Vikersund, Norway. EM pal.ulvenes@modum-bad.no NR 42 TC 8 Z9 8 U1 0 U2 4 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-0167 J9 J COUNS PSYCHOL JI J. Couns. Psychol. PD OCT PY 2012 VL 59 IS 4 BP 638 EP 644 DI 10.1037/a0030037 PG 7 WC Psychology, Educational; Psychology, Applied SC Psychology GA 024RR UT WOS:000310126800014 PM 23088686 ER PT J AU Choi, EY Yeo, BTT Buckner, RL AF Choi, Eun Young Yeo, B. T. Thomas Buckner, Randy L. TI The organization of the human striatum estimated by intrinsic functional connectivity SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE somatotopy; limbic network; prefrontal cortex; association cortex; fMRI; functional connectivity; default network ID HUMAN CEREBRAL-CORTEX; PRIMARY MOTOR CORTEX; FRONTAL EYE FIELD; INFERIOR PARIETAL LOBULE; SURFACE-BASED ANALYSIS; DEMENTED OLDER-ADULTS; OPEN ACCESS SERIES; MACAQUE MONKEY; BASAL-GANGLIA; CORTICOSTRIATAL PROJECTIONS AB Choi EY, Yeo BT, Buckner RL. The organization of the human striatum estimated by intrinsic functional connectivity. J Neurophysiol 108: 2242-2263, 2012. First published July 25, 2012; doi:10.1152/jn.00270.2012.-The striatum is connected to the cerebral cortex through multiple anatomical loops that process sensory, limbic, and heteromodal information. Tract-tracing studies in the monkey reveal that these corticostriatal connections form stereotyped patterns in the striatum. Here the organization of the striatum was explored in the human with resting-state functional connectivity MRI (fcMRI). Data from 1,000 subjects were registered with nonlinear deformation of the striatum in combination with surface-based alignment of the cerebral cortex. fcMRI maps derived from seed regions placed in the foot and tongue representations of the motor cortex yielded the expected inverted somatotopy in the putamen. fcMRI maps derived from the supplementary motor area were located medially to the primary motor representation, also consistent with anatomical studies. The topography of the complete striatum was estimated and replicated by assigning each voxel in the striatum to its most strongly correlated cortical network in two independent groups of 500 subjects. The results revealed at least five cortical zones in the striatum linked to sensorimotor, premotor, limbic, and two association networks with a topography globally consistent with monkey anatomical studies. The majority of the human striatum was coupled to cortical association networks. Examining these association networks further revealed details that fractionated the five major networks. The resulting estimates of striatal organization provide a reference for exploring how the striatum contributes to processing motor, limbic, and heteromodal information through multiple large-scale corticostriatal circuits. C1 [Choi, Eun Young] Harvard Univ, Div Med Sci, Program Neurosci, Cambridge, MA 02138 USA. [Choi, Eun Young; Yeo, B. T. Thomas; Buckner, Randy L.] Harvard Univ, Dept Psychol, Ctr Brain Sci, Cambridge, MA 02138 USA. [Choi, Eun Young; Yeo, B. T. Thomas; Buckner, Randy L.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Yeo, B. T. Thomas] Duke NUS Grad Med Sch, Neurosci & Behav Disorders Program, Singapore, Singapore. [Buckner, Randy L.] Howard Hughes Med Inst, Cambridge, MA USA. [Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Buckner, RL (reprint author), Harvard Univ, Div Med Sci, Program Neurosci, 52 Oxford St,Northwest Bldg 280-06, Cambridge, MA 02138 USA. EM randy_buckner@harvard.edu OI Choi, Eun Young/0000-0003-3226-1486; Yeo, B.T. Thomas/0000-0002-0119-3276 FU Advanced Multimodal Neuroimaging Training Program; National Science Foundation; National Institutes of Health (NIH) [AG-021910, A6-034556, P41-RR-14074, K08-MH-067966]; Massachusetts General Hospital-University of California, Los Angeles Human Connectome Project [U54MH091665]; Howard Hughes Medical Institute; Simons Foundation FX We thank Fenna Krienen and Avram Holmes for discussion, Koene Van Dijk for helpful comments on the manuscript, the Harvard Center for Brain Science Neuroimaging Core and the Athinoula A. Martinos Center for imaging support, the Harvard FAS Research Computing Group (in particular James Cuff, Brian Mantenuto, and Luis Silva), and the Harvard Neuroinformatics Research Group (Gabriele Fariello, Timothy O'Keefe, and Victor Petrov). We thank Haderer & Muller Biomedical Art for anatomic illustrations. E. Y. Choi was supported by fellowships from the Advanced Multimodal Neuroimaging Training Program and the National Science Foundation.; This work was supported by National Institutes of Health (NIH) Grants AG-021910, A6-034556, P41-RR-14074, and K08-MH-067966, the Massachusetts General Hospital-University of California, Los Angeles Human Connectome Project (U54MH091665), the Howard Hughes Medical Institute, and the Simons Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH. NR 106 TC 110 Z9 111 U1 8 U2 41 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD OCT PY 2012 VL 108 IS 8 BP 2242 EP 2263 DI 10.1152/jn.00270.2012 PG 22 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 023TD UT WOS:000310057500014 PM 22832566 ER PT J AU Scremin, OU Norman, KM Roch, M Holschneider, DP Scremin, AME AF Scremin, Oscar U. Norman, Keith M. Roch, Margareth Holschneider, Daniel P. Scremin, A. M. Erika TI Acetylcholinesterase Inhibition Interacts with Training To Reverse Spatial Learning Deficits after Cortical Impact Injury SO JOURNAL OF NEUROTRAUMA LA English DT Article DE acetylcholinesterase; cholinergic; neurorehabilitation; traumatic brain injury; spatial learning ID TRAUMATIC BRAIN-INJURY; CLOSED-HEAD-INJURY; RAT MODEL; CHOLINERGIC MARKERS; CONTUSION INJURY; WORKING MEMORY; MESSENGER-RNA; LONG-TERM; DONEPEZIL; NEURONS AB Cholinergic mechanisms are known to play a key role in cognitive functions that are profoundly altered in traumatic brain injury (TBI). The present investigation was designed to test the ability of continuous administration, starting at the time of injury, of physostigmine (PHY), an acetylcholinesterase (AChE) inhibitor that crosses the blood-brain barrier (BBB), to ameliorate the alterations of learning and memory induced by cerebral cortex impact injury in rats under isoflurane anesthesia. Learning and memory were assessed with the Morris water maze implemented during days 7-11 (WM1), and days 21-25 post-TBI (WM2), with four trials per day for 3 days, followed by target reversal and 2 additional days of training. These groups of Sprague-Dawley male rats were used: TBI treated with PHY at 3.2 mu mol/kg/day (TBI-PHY3.2), or 6.4 mu mol/kg/day (TBI-PHY6.4), by subcutaneous osmotic pumps, or TBI and no injury (Sham) treated with saline. AChE activity was measured in brain tissue samples of non-traumatized animals that received PHY at the doses used in the TBI animals. In WM1 tests, PHY3.2 improved learning within sessions, but not between sessions, in the recall of the target position, while PHY6.4 had no significant effects. In WM2 tests, PHY improved within- and between-sessions performance at both dose levels. We found that continuous AChE inhibition interacted with repeated training on the water maze task to completely reverse the deficits seen in learning and memory induced by TBI. The PHY treatment also reduced the amount of brain tissue loss as measured using cresyl violet staining. C1 [Scremin, Oscar U.; Norman, Keith M.; Roch, Margareth] Vet Affairs Greater Los Angeles Healthcare Syst, Res, Los Angeles, CA 90073 USA. [Scremin, A. M. Erika] Vet Affairs Greater Los Angeles Healthcare Syst, Phys Med & Rehabil Serv, Los Angeles, CA 90073 USA. [Scremin, Oscar U.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA. [Scremin, A. M. Erika] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Holschneider, Daniel P.] Univ So Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. [Holschneider, Daniel P.] Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90033 USA. [Holschneider, Daniel P.] Univ So Calif, Keck Sch Med, Dept Cell & Neurobiol, Los Angeles, CA 90033 USA. RP Scremin, OU (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Res, 11301 Wilshire Blvd,Bldg 115,Room 319, Los Angeles, CA 90073 USA. EM oscremin@ucla.edu FU Department of Veterans Affairs Rehabilitation Research & Development Merit Review (VA RRD) [B5089R]; VA RR&D Research Career Scientist award FX This work was supported by Department of Veterans Affairs Rehabilitation Research & Development Merit Review (VA RR&D) #B5089R, and a VA RR&D Research Career Scientist award (to O.U.S.). NR 58 TC 5 Z9 5 U1 1 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD OCT PY 2012 VL 29 IS 15 BP 2457 EP 2464 DI 10.1089/neu.2012.2465 PG 8 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 022NY UT WOS:000309967300003 PM 22738336 ER PT J AU Weiner, RB Weyman, AE Kim, JH Wang, TJ Picard, MH Baggish, AL AF Weiner, Rory B. Weyman, Arthur E. Kim, Jonathan H. Wang, Thomas J. Picard, Michael H. Baggish, Aaron L. TI The impact of isometric handgrip testing on left ventricular twist mechanics SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID SPECKLE TRACKING ECHOCARDIOGRAPHY; INOTROPIC STIMULATION; MYOCARDIAL-INFARCTION; APICAL ROTATION; HEART-RATE; TORSION; HUMANS; PRESSURE; EXERCISE; PRELOAD AB Key points Left ventricular twist (LVT) results from rotation of the LV apex and base in opposite directions. Although LVT is altered in various cardiac diseases, physiological factors that affect LVT remain incompletely understood. In an experimental model involving healthy humans, isometric handgrip testing (IHGT) was performed to produce a clinically relevant form of LV afterload increase. The impact of IHGT on LV twist mechanics was assessed using speckle-tracking echocardiography. IHGT produced significant increase in systemic blood pressure and acute reduction in LV stroke volume. In this setting, LV apical rotation and LVT significantly decreased. Impairment of LV twist mechanics may in part underlie the LV dysfunction that can occur in the clinical context of acute increase in afterload. Abstract Left ventricular (LV) rotation occurs due to contraction of obliquely oriented myocardial fibres. Left ventricular twist (LVT) results from rotation of the apex and base in opposite directions. Although LVT is altered in various cardiac diseases, physiological factors that affect LVT remain incompletely understood. Isometric handgrip testing (IHGT), a well-established laboratory-based technique to increase LV afterload, was performed for 3 min at 40% maximum force generation in healthy human subjects (n= 18, mean age 29.7 +/- 2.7 years). Speckle-tracking echocardiography was used to measure LV volumes, LV apical and basal rotation, peak systolic LVT and peak early diastolic untwisting rate (UTR) at rest and at peak IHGT. IHGT led to significant increase in systemic blood pressure (systolic, 120.6 +/- 9.7 vs. 155.6 +/- 14.5 mmHg, P < 0.001; diastolic, 67.5 +/- 6.4 vs. 94.1 +/- 21.1 mmHg, P < 0.001) and LV end-systolic volume (44.2 +/- 7.8 vs. 50.5 +/- 10.8 ml, P= 0.005), as well as a significant increase in heart rate (62.8 +/- 11.7 vs. 84.7 +/- 13.8 beats min-1; P < 0.001). IHGT produced a significant acute reduction in LV stroke volume (63.9 +/- 12.0 vs. 49.4 +/- 7.8 ml, P < 0.001). In this setting, there was a significant decrease in peak systolic apical rotation (11.9 +/- 3.0 vs. 8.6 +/- 2.2 deg, P < 0.001) and a resultant 25% decrease in peak systolic LVT (16.6 +/- 2.8 vs. 12.5 +/- 2.8 deg, P < 0.001). The magnitude of peak early diastolic UTR did not change (-114.5 +/- 26.4 vs. -110.6 +/- 39.8 deg s-1, P= 0.71). Peak systolic apical rotation and LVT decrease during IHGT in healthy humans. This impairment of LV twist mechanics may in part underlie the LV dysfunction that can occur in the clinical context of acute increase in afterload. C1 [Weiner, Rory B.] Massachusetts Gen Hosp, Cardiovasc Performance Program, Div Cardiol, Boston, MA 02114 USA. RP Weiner, RB (reprint author), Massachusetts Gen Hosp, Cardiovasc Performance Program, Div Cardiol, Yawkey Suite 5B,55 Fruit St, Boston, MA 02114 USA. EM rweiner@partners.org OI Picard, Michael/0000-0002-9264-3243 FU American Society of Echocardiography [10-G-16]; American Heart Association [09FTF2220328] FX This work was supported by Career Development Award grant number 10-G-16 from the American Society of Echocardiography (R. B. W.) and grant number 09FTF2220328 from the American Heart Association (A. L. B). The authors have no conflicts of interest to report. NR 35 TC 16 Z9 16 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD OCT PY 2012 VL 590 IS 20 BP 5141 EP 5150 DI 10.1113/jphysiol.2012.236166 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 021UD UT WOS:000309910000018 PM 22890704 ER PT J AU Carlos, RC Buist, DSM Wernli, KJ Swan, JS AF Carlos, Ruth C. Buist, Diana S. M. Wernli, Karen J. Swan, J. Shannon TI Patient-Centered Outcomes in Imaging: Quantifying Value SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Patient-centered; outcomes; value; health care reform ID PROCESS UTILITY; SERVICES AB The Patient-Centered Outcomes Research Institute was created in response to a mandate to conduct comparative effectiveness research in clinical care to inform decision making. The institute will be funded by the Patient-Centered Outcomes Research Trust Fund, through congressional set-asides, and by Medicare and private health insurers, through a per beneficiary fee. The institute is governed by a board with a broad stakeholder constitution. Key committees set the national agenda for patient-centered outcomes research, the agenda for funding priorities, and communication and dissemination of the evidence with the goal of increasing the rate of implementation of the evidence into policy. In imaging, patient-centered outcomes go beyond the traditional metrics of patient satisfaction. Instead, these outcomes need to encompass the benefits and harms, focus on outcomes relevant to patients, and provide information to inform decision making. Therefore, radiologists need to be involved as stakeholders in the design, conduct, and dissemination of this research. C1 [Carlos, Ruth C.] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [Buist, Diana S. M.; Wernli, Karen J.] Grp Hlth Res Inst, Seattle, WA USA. [Buist, Diana S. M.; Wernli, Karen J.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Swan, J. Shannon] Harvard Univ, Sch Med, Boston, MA USA. [Swan, J. Shannon] Inst Technol Assessment, Boston, MA USA. [Swan, J. Shannon] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Carlos, RC (reprint author), Univ Michigan, Dept Radiol, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM rcarlos@med.umich.edu FU National Cancer Institute [1 R21 CA133333]; National Institutes of Health [RC2CA1484331, RC2CA148577, RC2CA148576]; Agency for Healthcare Research and Quality [K12 HS019482]; American Cancer Society [114130-RSGHP-07-266-01-CPHPS]; Massachusetts General Hospital Executive Committee on Research Bridge Fund [1200-218421] FX Dr Carlos is funded in part by grant 1 R21 CA133333 from the National Cancer Institute. Dr Buist is funded in part by grants RC2CA1484331, RC2CA148577, and RC2CA148576 from the National Institutes of Health. Dr Wernli is funded in part by grant K12 HS019482 from the Agency for Healthcare Research and Quality. Dr Swan is funded in part by grant 114130-RSGHP-07-266-01-CPHPS from the American Cancer Society and Massachusetts General Hospital Executive Committee on Research Bridge Fund 1200-218421. NR 13 TC 14 Z9 14 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD OCT PY 2012 VL 9 IS 10 BP 725 EP 728 DI 10.1016/j.jacr.2012.06.008 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 022UQ UT WOS:000309989700015 PM 23025867 ER PT J AU Hoffmann, U Venkatesh, V White, RD Woodard, PK Carr, JJ Dorbala, S Earls, JP Jacobs, JE Mammen, L Martin, ET Ryan, T White, CS AF Hoffmann, Udo Venkatesh, Vikram White, Richard D. Woodard, Pamela K. Carr, J. Jeffrey Dorbala, Sharmila Earls, James P. Jacobs, Jill E. Mammen, Leena Martin, Edward T., III Ryan, Thomas White, Charles S. TI ACR Appropriateness Criteria (R) Acute Nonspecific Chest Pain-Low Probability of Coronary Artery Disease SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Appropriateness criteria; low-risk acute chest pain; radiation exposure; computed tomography; clinical indications ID EMERGENCY-DEPARTMENT PATIENTS; SUSPECTED PULMONARY-EMBOLISM; CARDIAC COMPUTED-TOMOGRAPHY; RANDOMIZED CONTROLLED-TRIAL; MAGNETIC-RESONANCE; CT ANGIOGRAPHY; DIAGNOSTIC-ACCURACY; AORTIC DISSECTION; ECHOCARDIOGRAPHY; EVENTS AB This document outlines the usefulness of available diagnostic imaging for patients without known coronary artery disease and at low probability for having coronary artery disease who do not present with classic signs, symptoms, or electrocardiographic abnormalities indicating acute coronary syndrome but rather with nonspecific chest pain leading to a differential diagnosis, including pulmonary, gastrointestinal, or musculoskeletal pathologies. A number of imaging modalities are available to evaluate the broad spectrum of possible pathologies in these patients, such as chest radiography, multidetector CT, MRI, ventilation-perfusion scans, cardiac perfusion scintigraphy, transesophageal and transthoracic echocardiography, PET, spine and rib radiography, barium esophageal and upper gastrointestinal studies, and abdominal ultrasound. It is considered appropriate to start the assessment of these patients with a low-cost, low-risk diagnostic test such as a chest x-ray. Contrast-enhanced gated cardiac and ungated thoracic multidetector CT as well as transthoracic echocardiography are also usually considered as appropriate in the evaluation of these patients as a second step if necessary. A number of rest and stress single-photon emission CT myocardial perfusion imaging, ventilation-perfusion scanning, aortic and chest MR angiographic, and more specific x-ray and abdominal examinations may be appropriate as a third layer of testing, whereas MRI of the heart or coronary arteries and invasive testing such as transesophageal echocardiography or selective coronary angiography are not considered appropriate in these patients. Given the low risk of these patients, it is mandated to minimize radiation exposure as much as possible using advanced and appropriate testing protocols. The ACR Appropriateness Criteria (R) are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a wellestablished consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. C1 [Hoffmann, Udo; Venkatesh, Vikram] Massachusetts Gen Hosp, Boston, MA 02114 USA. [White, Richard D.] Ohio State Univ, Coll Med, Columbus, OH 43210 USA. [Woodard, Pamela K.] Washington Univ, Sch Med, Edward Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. [Carr, J. Jeffrey] Wake Forest Univ Hlth Sci, Winston Salem, NC USA. [Dorbala, Sharmila] Brigham & Womens Hosp, Boston, MA 02115 USA. [Dorbala, Sharmila] Soc Nucl Med & Mol Imaging, Reston, VA USA. [Earls, James P.] Fairfax Radiol Consultants, Fairfax, VA USA. [Jacobs, Jill E.] NYU, Med Ctr, New York, NY 10016 USA. [Mammen, Leena] Adv Radiol Serv, Grand Rapids, MI USA. [Martin, Edward T., III] Oklahoma Heart Inst, Tulsa, OK USA. [Martin, Edward T., III; Ryan, Thomas] Amer Coll Cardiol, Bethesda, MD USA. [Ryan, Thomas] Ohio State Univ, Heart & Vasc Ctr, Columbus, OH 43210 USA. [White, Charles S.] Univ Maryland Hosp, Baltimore, MD 21201 USA. RP Hoffmann, U (reprint author), Amer Coll Radiol, 1891 Preston White Dr, Reston, VA 20191 USA. EM uhoffmann@partners.org RI Carr, John/A-1938-2012; OI Carr, John/0000-0002-4398-8237; White, Richard D./0000-0002-1133-7819 NR 58 TC 7 Z9 7 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD OCT PY 2012 VL 9 IS 10 BP 745 EP 750 DI 10.1016/j.jacr.2012.06.032 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 022UQ UT WOS:000309989700019 PM 23025871 ER PT J AU Steinman, MA Lee, SJ Boscardin, WJ Miao, YH Fung, KZ Moore, KL Schwartz, JB AF Steinman, Michael A. Lee, Sei J. Boscardin, W. John Miao, Yinghui Fung, Kathy Z. Moore, Kelly L. Schwartz, Janice B. TI Patterns of Multimorbidity in Elderly Veterans SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE multimorbidity; aged; veterans; age effects ID MULTIPLE CHRONIC CONDITIONS; QUALITY-OF-CARE; CHRONIC DISEASES; PREVALENCE; COMORBIDITY; POPULATION; MANAGEMENT; CONSEQUENCES; PERFORMANCE; COMPLEXITY AB Objectives To determine patterns of co-occurring diseases in older adults and the extent to which these patterns vary between the young-old and the old-old. Design Observational study. Setting Department of Veterans Affairs. Participants Veterans aged 65 years and older (1.9 million male, mean age 76 +/- 7; 39,000 female, mean age 77 +/- 8) with two or more visits to Department of Veterans Affairs (VA) or Medicare settings in 2007 and 2008. Measurements The presence of 23 common conditions was assessed using hospital discharge diagnoses and outpatient encounter diagnoses from the VA and Medicare. Results The mean number of chronic conditions (out of 23 possible) was 5.5 +/- 2.6 for men and 5.1 +/- 2.6 for women. The prevalence of most conditions increased with advancing age, although diabetes mellitus and hyperlipidemia were 11% to 13% less prevalent in men and women aged 85 and older than in those aged 65 to 74 (P < .001 for each). In men, the most common three-way combination of conditions was hypertension, hyperlipidemia, and coronary heart disease, which together were present in 37% of men. For women, the most common combination was hypertension, hyperlipidemia, and arthritis, which co-occurred in 25% of women. Reflecting their high population prevalence, hypertension and hyperlipidemia were both present in 9 of the 15 most common three-way disease combinations in men and in 11 of the 15 most common combinations in women. The prevalence of many disease combinations varied substantially between young-old and old-old adults. Conclusions Specific combinations of diseases are highly prevalent in older adults and inform the development of guidelines that account for the simultaneous presence of multiple chronic conditions. C1 [Steinman, Michael A.; Lee, Sei J.; Boscardin, W. John; Miao, Yinghui; Fung, Kathy Z.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Schwartz, Janice B.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Steinman, Michael A.; Lee, Sei J.; Boscardin, W. John; Miao, Yinghui; Fung, Kathy Z.] San Francisco VA Med Ctr, Hlth Serv Res Enhancement Award Program, San Francisco, CA USA. [Moore, Kelly L.; Schwartz, Janice B.] Jewish Home San Francisco, San Francisco, CA USA. RP Steinman, MA (reprint author), 4150 Clement St,SFVAMC Box 181G, San Francisco, CA 94121 USA. EM Mike.steinman@ucsf.edu FU National Institute on Aging (NIA) [RC1-AG036377]; University of California at San Francisco; NIA; American Federation for Aging Research [1K23-AG030999, K23AG040779]; San Francisco VA Medical Center FX This work was presented at the national meeting of the American Geriatrics Society, National Harbor, Maryland, 2011. Any opinions expressed in this work do not represent the official position of the VA. This work was supported National Institute on Aging (NIA) Grant RC1-AG036377, the University of California at San Francisco KL2 Career Development Program, Paul B. Beeson Career Development Awards from the NIA and the American Federation for Aging Research (1K23-AG030999 and K23AG040779), and the Health Services Research and Development Research Enhancement Award Program at the San Francisco VA Medical Center. NR 37 TC 45 Z9 45 U1 3 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 2012 VL 60 IS 10 BP 1872 EP 1880 DI 10.1111/j.1532-5415.2012.04158.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 019LF UT WOS:000309740400010 PM 23035702 ER PT J AU Weisberg, E Liu, Q Nelson, E Kung, AL Christie, AL Bronson, R Sattler, M Sanda, T Zhao, Z Hur, W Mitsiades, C Smith, R Daley, JF Stone, R Galinsky, I Griffin, JD Gray, N AF Weisberg, E. Liu, Q. Nelson, E. Kung, A. L. Christie, A. L. Bronson, R. Sattler, M. Sanda, T. Zhao, Z. Hur, W. Mitsiades, C. Smith, R. Daley, J. F. Stone, R. Galinsky, I. Griffin, J. D. Gray, N. TI Using combination therapy to override stromal-mediated chemoresistance in mutant FLT3-positive AML: synergism between FLT3 inhibitors, dasatinib/multi-targeted inhibitors and JAK inhibitors SO LEUKEMIA LA English DT Article DE acute myeloid leukemia; multi-targeted kinase inhibitor; PKC412; AC220; stromal-mediated chemoresistance; synergy ID ACUTE MYELOID-LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; INTERNAL TANDEM DUPLICATION; TYROSINE KINASE INHIBITOR; BONE-MARROW STROMA; SRC FAMILY KINASES; CELL-LINES; B-CELLS; ANTILEUKEMIC THERAPIES; FLT3-EXPRESSING CELLS AB Acute myeloid leukemia (AML) progenitors are frequently characterized by activating mutations in the receptor tyrosine kinase Fms-like tyrosine kinase-3 (FLT3). Protein tyrosine kinases are integral components of signaling cascades that have a role in both FLT3-mediated transformation as well as viability pathways that are advantageous to leukemic cell survival. The bone marrow microenvironment can diminish AML sensitivity to tyrosine kinase inhibitors. We hypothesized that inhibition of protein kinases in addition to FLT3 may be effective in overriding drug resistance in AML. We used a cell-based model mimicking stromal protection as part of an unbiased high-throughput chemical screen to identify kinase inhibitors with the potential to override microenvironment-mediated drug resistance in mutant FLT3-positive AML. Several related multi-targeted kinase inhibitors, including dasatinib, with the capability of reversing microenvironment-induced resistance to FLT3 inhibition were identified and validated. We validated synergy in vitro and demonstrated effective combination potential in vivo. In particular Janus kinase inhibitors were effective in overriding stromal protection and potentiating FLT3 inhibition in primary AML and cell lines. These results hint at a novel concept of using combination therapy to override drug resistance in mutant FLT3-positive AML in the bone marrow niche and suppress or eradicate residual disease. Leukemia (2012) 26, 2233-2244; doi:10.1038/leu.2012.96 C1 [Weisberg, E.; Nelson, E.; Sattler, M.; Sanda, T.; Mitsiades, C.; Smith, R.; Daley, J. F.; Stone, R.; Galinsky, I.; Griffin, J. D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Liu, Q.; Hur, W.; Gray, N.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02215 USA. [Kung, A. L.; Christie, A. L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Kung, A. L.; Christie, A. L.] Childrens Hosp, Boston, MA 02115 USA. [Bronson, R.] Harvard Univ, Sch Med, Dept Pathol, Rodent Histopathol Core, Boston, MA 02215 USA. [Zhao, Z.] Chinese Acad Sci, High Magnet Field Lab, Hefei, Anhui, Peoples R China. RP Griffin, JD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave Boston,02215 Mailstop Mayer 540, Boston, MA 02215 USA. EM james_griffin@dfci.harvard.edu; nathanael_gray@dfci.harvard.edu OI liu, qing song/0000-0002-7829-2547; Kung, Andrew/0000-0002-9091-488X FU NIH [CA66996]; NIH LINCS Grant [HG006097, R01 CA130876-02] FX We wish to thank Feiyang Liu for her technical assistance. We thank DiscoveRx Bioscience for performing KinomeScan profiling and the Treespot view image was generated using the web-based TREEspot software (DiscoveRx Biosciences). JDG is supported by NIH grant CA66996. QL and NSG are supported by NIH LINCS Grant HG006097 and R01 CA130876-02. NR 55 TC 23 Z9 24 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD OCT PY 2012 VL 26 IS 10 BP 2233 EP 2244 DI 10.1038/leu.2012.96 PG 12 WC Oncology; Hematology SC Oncology; Hematology GA 022KM UT WOS:000309958300010 PM 22469781 ER PT J AU Adeyi, O Alexander, G Baiocchi, L Balasubramanian, M Batal, I Bellamy, COC Bhan, A Bridges, N Bucuvalas, J Charlotte, F Colvin, B Czaja, A Demetris, A DeVera, M El-Monayeri, MS Feng, S Ferrell, L Fiel, MI Fontes, P Fung, J Haga, H Hart, J Honsova, E Hubscher, S Wesam, I Itoh, T Jhala, N Jungmann, P Khettry, U Koshiba, T Lassman, C Lerut, J Ligato, S Lunz, J Mazariegos, G McCaughan, G McClelland, SA Minervini, MI Misdraji, J Mohanakumar, T Molne, J Musat, A Nalesnik, M Nasser, I Neil, D Neuberger, J Pappo, O Petrovic, L Randhawa, P Reinholt, FP Rubin, E Ruiz, P Sagol, O Fueyo, AS Sasatomi, E Schiano, T Sebagh, M Shaked, A Sharkey, FE Shimizu, T Sis, B Smith, M Sonzogni, A Tchao, N Thung, S Tisone, G Tsamandas, A Wernerson, A Wu, T Yilmaz, F AF Adeyi, Oyedele Alexander, Graeme Baiocchi, Leonardo Balasubramanian, Manjula Batal, Ibrahim Bellamy, Chris O. C. Bhan, Atul Bridges, Nancy Bucuvalas, John Charlotte, Frederic Colvin, Bob Czaja, Albert Demetris, Anthony DeVera, Michael El-Monayeri, Magda S. Feng, Sandy Ferrell, Linda Fiel, Maria Isabel Fontes, Paulo Fung, John Haga, Hironori Hart, John Honsova, Eva Hubscher, Stefan Wesam, Ismail Itoh, Tomoo Jhala, Nirag Jungmann, Patricia Khettry, Urmila Koshiba, Takaaki Lassman, Charles Lerut, Jan Ligato, Saverio Lunz, John Mazariegos, George McCaughan, Geoff McClelland, Sandra A. Minervini, Marta I. Misdraji, Joseph Mohanakumar, Thalachallour Molne, Johan Musat, Alexandru Nalesnik, Michael Nasser, Imad Neil, Desley Neuberger, James Pappo, Orit Petrovic, Lydia Randhawa, Parmjeet Reinholt, Finn P. Rubin, Erin Ruiz, Phil Sagol, Ozgul Sanchez Fueyo, Alberto Sasatomi, Eizaburo Schiano, Thomas Sebagh, Mylene Shaked, Avi Sharkey, Francis Edward Shimizu, Tomokazu Sis, Banu Smith, Maxwell Sonzogni, Aurelio Tchao, Nadia Thung, Swan Tisone, Giuseppe Tsamandas, Athanassios Wernerson, Annika Wu, Tong Yilmaz, Funda CA Banff Working Grp Liver Allograft TI Importance of liver biopsy findings in immunosuppression management: Biopsy monitoring and working criteria for patients with operational tolerance SO LIVER TRANSPLANTATION LA English DT Review ID RECURRENT HEPATITIS-C; LONG-TERM OUTCOMES; NOVO AUTOIMMUNE HEPATITIS; CHRONIC VIRAL-HEPATITIS; PLASMA-CELL HEPATITIS; REGULATORY T-CELLS; TRANSPLANT RECIPIENTS; FOLLOW-UP; ALLOGRAFT-REJECTION; GRAFT FIBROSIS AB Obstacles to morbidity-free long-term survival after liver transplantation (LT) include complications of immunosuppression (IS), recurrence of the original disease and malignancies, and unexplained chronic hepatitis and graft fibrosis. Many programs attempt to minimize chronic exposure to IS by reducing dosages and stopping steroids. A few programs have successfully weaned a highly select group of recipients from all IS without apparent adverse consequences, but long-term follow-up is limited. Patients subjected to adjustments in IS are usually followed by serial liver chemistry tests, which are relatively insensitive methods for detecting allograft damage. Protocol biopsy has largely been abandoned for hepatitis C virusnegative recipients, at least in part because of the inability to integrate routine histopathological findings into a rational clinical management algorithm. Recognizing a need to more precisely categorize and determine the clinical significance of findings in long-term biopsy samples, the Banff Working Group on Liver Allograft Pathology has reviewed the literature, pooled the experience of its members, and proposed working definitions for biopsy changes that (1) are conducive to lowering IS and are compatible with operational tolerance (OT) and (2) raise concern for closer follow-up and perhaps increased IS during or after IS weaning. The establishment of guidelines should help us to standardize analyses of the effects of various treatments and/or weaning protocols and more rigorously categorize patients who are assumed to show OT. Long-term follow-up using standardized criteria will help us to determine the consequences of lowering IS and to define and determine the incidence and robustness of OT in liver allografts. Liver Transpl 18:1154-1170, 2012. (c) 2012 AASLD. C1 [Demetris, Anthony; Fontes, Paulo; Lunz, John; Mazariegos, George; McClelland, Sandra A.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. [Adeyi, Oyedele] Toronto Gen Hosp, Toronto, ON, Canada. [Alexander, Graeme] Univ Cambridge, Cambridge CB2 1TN, England. [Baiocchi, Leonardo] Univ Roma Tor Vergata, Rome, Italy. [Balasubramanian, Manjula] Albert Einstein Med Ctr, Philadelphia, PA 19141 USA. [Batal, Ibrahim] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bellamy, Chris O. C.] Edinburgh Royal Infirm, Edinburgh, Midlothian, Scotland. [Bhan, Atul; Colvin, Bob] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Bridges, Nancy] NIAID, Bethesda, MD 20892 USA. [Bucuvalas, John] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Charlotte, Frederic] Hop La Pitie Salpetriere, Paris, France. [Czaja, Albert] Mayo Clin, Coll Med, Rochester, MN 55905 USA. [DeVera, Michael] Loma Linda Univ, Loma Linda, CA 92350 USA. [Feng, Sandy; Ferrell, Linda] Univ Calif San Francisco, Ctr Med, San Francisco, CA 94143 USA. [Fiel, Maria Isabel] Mt Sinai Sch Med, New York, NY USA. [Fung, John] Cleveland Clin Fdn, Cleveland, OH USA. [Haga, Hironori] Kyoto Univ Hosp, Kyoto, Japan. [Hart, John] Univ Chicago, Ctr Med, Chicago, IL 60637 USA. [Honsova, Eva] Inst Clin & Expt Med, Prague, Czech Republic. [Hubscher, Stefan] Univ Birmingham, Birmingham B15 2TT, W Midlands, England. [Wesam, Ismail] Bani Sweif Univ, Bani Suwayf, Egypt. [Itoh, Tomoo] Hokkaido Univ Hosp, Sapporo, Hokkaido, Japan. [Jhala, Nirag] Univ Alabama Birmingham, Birmingham, AL USA. [Jungmann, Patricia] Univ Fed Pernambuco, Recife, PE, Brazil. [Koshiba, Takaaki] Kyoto Univ, Kyoto 6068501, Japan. [Lassman, Charles] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Ligato, Saverio] Hartford Hosp, Hartford, CT USA. [McCaughan, Geoff] Univ Sydney, Royal Prince Alfred Hosp, Sydney, NSW 2006, Australia. [Mohanakumar, Thalachallour] Washington Univ, St Louis, MO 63130 USA. [Molne, Johan] Sahlgrens Univ Hosp, Gothenburg, Sweden. [Musat, Alexandru] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Nasser, Imad] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Cambridge, MA 02138 USA. [Neil, Desley; Neuberger, James] Univ Hosp Birmingham, Birmingham, W Midlands, England. [Pappo, Orit] Hadassah Med Ctr, Jerusalem, Israel. [Petrovic, Lydia] Univ So Calif, Univ Hosp, Los Angeles, CA 90089 USA. [Ruiz, Phil] Univ Miami, Sch Med, Coral Gables, FL 33124 USA. [Reinholt, Finn P.] Univ Oslo, N-0316 Oslo, Norway. [Reinholt, Finn P.] Oslo Univ Univ, Rikshosp, Oslo, Norway. [Sagol, Ozgul] Dokuz Eylul Univ, TR-35210 Alsancak, Turkey. [Sanchez Fueyo, Alberto] Hosp Clin Barcelona, Liver Transplant Unit, Barcelona, Spain. [Schiano, Thomas; Thung, Swan] Mt Sinai Med Ctr, New York, NY USA. [Sebagh, Mylene] Hop Paul Brousse, Villejuif, France. [Shaked, Avi] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Sharkey, Francis Edward] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Shimizu, Tomokazu] Tokyo Womens Med Univ, Tokyo, Japan. [Sis, Banu] Univ Alberta Hosp, Edmonton, AB, Canada. [Sonzogni, Aurelio] Univ Pittsburgh, Med Ctr, Palermo, Italy. [Tisone, Giuseppe] Univ Rome, Rome, Italy. [Tsamandas, Athanassios] Univ Patras, Sch Med, GR-26110 Patras, Greece. [Wernerson, Annika] Karolinska Univ Hosp, Stockholm, Sweden. [Wu, Tong] Tulane Univ, Sch Med, New Orleans, LA 70118 USA. [Yilmaz, Funda] Univ Ege, Izmir, Turkey. RP Demetris, A (reprint author), Univ Pittsburgh, Med Ctr, 3459 5th Ave,UPMC Montefiore E741, Pittsburgh, PA 15213 USA. EM demetrisaj@upmc.edu RI Fung, John/A-2679-2012; OI Wernerson, Annika/0000-0003-2792-0010; Neil, Desley/0000-0001-9800-6811 NR 123 TC 28 Z9 28 U1 1 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1527-6465 EI 1527-6473 J9 LIVER TRANSPLANT JI Liver Transplant. PD OCT PY 2012 VL 18 IS 10 BP 1154 EP 1170 DI 10.1002/lt.23481 PG 17 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 021WS UT WOS:000309916700007 ER PT J AU Gruionu, G Hoying, JB Pries, AR Secomb, TW AF Gruionu, Gabriel Hoying, James B. Pries, Axel R. Secomb, Timothy W. TI Structural Remodeling of the Mouse Gracilis Artery: Coordinated Changes in Diameter and Medial Area Maintain Circumferential Stress SO MICROCIRCULATION LA English DT Article DE vascular adaptation; blood flow; ischemia; smooth muscle cells; endothelial cells ID MICROVASCULAR NETWORKS; RESISTANCE ARTERIES; BLOOD-FLOW; ARTERIOGENESIS; ADAPTATION; GROWTH; RAT; ANGIOGENESIS; OCCLUSION; RESPONSES AB Objective: Vascular networks respond to chronic alterations in blood supply by structural remodeling. Previously, we showed that blood flow changes in the mouse GA lead to transient diameter increases, which can generate large increases in circumferential wall stress. Here, we examine the associated changes in the medial area of the arterial wall and the effects on circumferential wall stress. Methods: To induce blood flow changes, one of the two feeding vessels to the GA was surgically removed. At 756 days after blood flow interruption, the vasculature was perfused with India ink for morphological measurements, and processed for immuno-cytochemistry to mark the medial cross-section area. Theoretical simulations of hemodynamics were used to analyze the data. Results: During adaptive increases in vessel diameter, increases in medial area were observed, most strongly in the middle region of the artery. Simulations showed that this increase in medial area limits the increase in estimated circumferential stress during vascular adaptation to less than 50%, in contrast to an increase of up to 250% if the medial area had remained unchanged. Conclusions: During vascular adaptation, increases in circumferential stress are limited by growth of the media coordinated with diameter changes. C1 [Gruionu, Gabriel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Edwin L Steele Lab Tumor Biol,Dept Radiat Oncol, Boston, MA USA. [Hoying, James B.] Cardiovasc Innovat Inst, Div Cardiovasc Therapeut, Louisville, KY USA. [Pries, Axel R.] Charite, Dept Physiol, D-13353 Berlin, Germany. [Pries, Axel R.] Charite, CCR, D-13353 Berlin, Germany. [Secomb, Timothy W.] Univ Arizona, Dept Physiol, Tucson, AZ USA. RP Gruionu, G (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Bldg 149,13th St,Room 3316, Charlestown, MA 02129 USA. EM gabi@steele.mgh.harvard.edu OI Secomb, Timothy/0000-0002-0176-5502 FU AHA [0010189Z]; NIH [HL034555, HL063732] FX This work was Supported by AHA grant 0010189Z and NIH grants HL034555 and HL063732. NR 28 TC 4 Z9 4 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1073-9688 J9 MICROCIRCULATION JI Microcirculation PD OCT PY 2012 VL 19 IS 7 BP 610 EP 618 DI 10.1111/j.1549-8719.2012.00194.x PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 019RJ UT WOS:000309756700005 PM 22587333 ER PT J AU Morley, JF Duda, JE AF Morley, James F. Duda, John E. TI Parkinson's disease and the risk of cerebrovascular pathology SO MOVEMENT DISORDERS LA English DT Editorial Material ID STROKE; LESIONS; HOMOCYSTEINE; PREVALENCE; POSTMORTEM C1 Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Perelman Sch Med, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Duda, JE (reprint author), Univ Penn, Sch Med, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. EM john.duda@med.va.gov NR 27 TC 5 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD OCT PY 2012 VL 27 IS 12 BP 1471 EP 1472 DI 10.1002/mds.25179 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 023VL UT WOS:000310064800001 PM 23033113 ER PT J AU Doraiswamy, PM Sperling, RA Coleman, RE Johnson, KA Reiman, EM Davis, MD Grundman, M Sabbagh, MN Sadowsky, CH Fleisher, AS Carpenter, A Clark, CM Joshi, AD Mintun, MA Skovronsky, DM Pontecorvo, MJ AF Doraiswamy, P. Murali Sperling, Reisa A. Coleman, R. Edward Johnson, Keith A. Reiman, Eric M. Davis, Mat D. Grundman, Michael Sabbagh, Marwan N. Sadowsky, Carl H. Fleisher, Adam S. Carpenter, Alan Clark, Christopher M. Joshi, Abhinay D. Mintun, Mark A. Skovronsky, Daniel M. Pontecorvo, Michael J. CA AV45-A11 Study Grp TI Amyloid-beta assessed by florbetapir F 18 PET and 18-month cognitive decline A multicenter study SO NEUROLOGY LA English DT Article ID PITTSBURGH COMPOUND-B; ALZHEIMERS ASSOCIATION WORKGROUPS; A-BETA; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; DISEASE; IMPAIRMENT; RECOMMENDATIONS; PROGRESSION AB Objectives: Florbetapir F 18 PET can image amyloid-beta (A beta) aggregates in the brains of living subjects. We prospectively evaluated the prognostic utility of detecting A beta pathology using florbetapir PET in subjects at risk for progressive cognitive decline. Methods: A total of 151 subjects who previously participated in a multicenter florbetapir PET imaging study were recruited for longitudinal assessment. Subjects included 51 with recently diagnosed mild cognitive impairment (MCI), 69 cognitively normal controls (CN), and 31 with clinically diagnosed Alzheimer disease dementia (AD). PET images were visually scored as positive (A beta+)or negative (A beta-) for pathologic levels of beta-amyloid aggregation, blind to diagnostic classification. Cerebral to cerebellar standardized uptake value ratios (SUVr) were determined from the baseline PET images. Subjects were followed for 18 months to evaluate changes in cognition and diagnostic status. Analysis of covariance and correlation analyses were conducted to evaluate the association between baseline PET amyloid status and subsequent cognitive decline. Results: In both MCI and CN, baseline A beta+ scans were associated with greater clinical worsening on the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog (p < 0.01) and Clinical Dementia Rating-sum of boxes (CDR-SB) (p < 0.02). In MCI A beta+ scans were also associated with greater decline in memory, Digit Symbol Substitution (DSS), and Mini-Mental State Examination (MMSE) (p < 0.05). In MCI, higher baseline SUVr similarly correlated with greater subsequent decline on the ADAS-Cog (p < 0.01), CDR-SB (p < 0.03), a memory measure, DSS, and MMSE (p < 0.05). A beta+ MCI tended to convert to AD dementia at a higher rate than A beta- subjects (p < 0.10). Conclusions: Florbetapir PET may help identify individuals at increased risk for progressive cognitive decline. Neurology (R) 2012; 79: 1636-1644 C1 [Doraiswamy, P. Murali; Coleman, R. Edward] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Sperling, Reisa A.; Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Davis, Mat D.] Univ Penn, Philadelphia, PA 19104 USA. [Reiman, Eric M.; Fleisher, Adam S.] Banner Alzheimers Inst, Phoenix, AZ USA. [Davis, Mat D.] Theorem Clin Res, King Of Prussia, PA USA. [Grundman, Michael] Global R&D Partners, San Diego, CA USA. [Grundman, Michael; Fleisher, Adam S.] Univ Calif San Diego, San Diego, CA 92103 USA. [Sabbagh, Marwan N.] Banner Sun Hlth Res Inst, Sun City, AZ USA. [Sadowsky, Carl H.] Nova SE Univ, Ft Lauderdale, FL 33314 USA. [Carpenter, Alan; Clark, Christopher M.; Joshi, Abhinay D.; Mintun, Mark A.; Skovronsky, Daniel M.; Pontecorvo, Michael J.] Avid Radiopharmaceut, Philadelphia, PA USA. RP Doraiswamy, PM (reprint author), Duke Univ, Med Ctr, Durham, NC 27706 USA. EM murali.doraiswamy@duke.edu; pontecorvo@avidrp.com FU Duke University from NIA; NIMH; NINDS; NHLBI; University of California (ADCS); Northern California Research Institute (ADNI); Avid/Lilly; Elan; Bristol-Myers; Ono; Sanofi; Novartis; Medivation; Neuronetrix; BristolMyers; Accera; Sonexa; Schering; TauRx; Baxter; Neuroptix; Bayer; Otsuka; AstraZeneca; Lundbeck; Edwards Hospital; Bristol-Myers-Squib; Janssen (JanssenAI); Pfizer; NIDDK [2T32DK060455]; Celgene; Ceregene; BMS; Lilly; Wyeth; Janssen; Avid; Genentech; Eisai FX P.M. Doraiswamy has received research grants through Duke University from NIA, NIMH, NINDS, NHLBI, University of California (ADCS), Northern California Research Institute (ADNI), Avid/Lilly, Elan, Bristol-Myers, Ono, Sanofi, Novartis, Medivation, and Neuronetrix in the recent past. He has received advisory or speaking fees from Avid/Lilly, Medivation, BristolMyers, Accera, Sonexa, Schering, TauRx, Baxter, Neuroptix, Bayer, Neuronetrix, Otsuka, AstraZeneca, Lundbeck, and Edwards Hospital. He owns stock in Sonexa, Clarimedix, and Adverse Events Inc, whose products are not discussed in this manuscript. R. A. Sperling has served as a site investigator for Avid, BMS, Elan, Janssen, Pfizer, and Wyeth and as a consultant to Bayer, BMS, Elan, Eisai, Janssen, Pfizer, Roche, and Wyeth, and as an unpaid consultant to Avid. She has received speaking honoraria from Prizer, Janssen, Eli Lilly, and Bayer. R. E. Coleman was a site PI for the clinical study and served on an advisory board to Avid and Lilly. K. A. Johnson was a co-investigator in the trial and has consulted for GE Healthcare, Bayer-Schering, Pfizer, Elan/Janssen, and Seimens. He has received research support from Avid/Lilly, Bristol-Myers-Squib, Janssen (JanssenAI), and Pfizer. E. M. Reiman has served as a scientific advisor to Sygnis, AstraZeneca, Bayer, Eisai, Elan, Eli Lilly, GlaxoSmithKline, Intellect, Link Medicine, Novartis, Siemens, and Takeda. He has had research contracts with NIA the Arizona Dept. of Health Services, AstraZeneca, and Avid. M. D. Davis has received training support from NIDDK grant 2T32DK060455, is an employee at Theorem Clinical Research, and performed statistical analyses under a contract from Avid. M. Grundman has served as a consultant to Acumen, Adamas, ALSP, Avid, Biogen Idec, Elan, Helicon, Intellect Neurosciences, Janssen Alzheimer Immunotherapy, J&J, Lilly, Neurophage, and Teva and on advisory boards for Helicon, Nutricia North America, and Bristol Myers Squibb. He owns stock in Elan and formerly held Avid stock options. M.N. Sabbagh has served in a consulting or advisory capacity for Lilly, Amerisciences, Takeda, Eisai, Pfizer, and GSK and has received royalties from Wiley and Amerisciences. He has received contracts and grants from Celgene, Ceregene, Bayer, Baxter, BMS, Lilly, Pfizer, Wyeth, Janssen, Elan, Avid, Genentech, and Eisai. C. H. Sadowsky has served on speaker bureaus for Novartis, Forest, and Accera and as a consultant to Lilly. A. S. Fleisher has served as a consultant to Lilly and Avid and received grant funding from Avid. A. Carpenter is an employee of Avid, a division of Eli Lilly, and formerly held Avid stock or options. C. M. Clark, deceased, was an employee at Avid; disclosures are not included for this author. A. D. Joshi, M. A. Mintun, D. M. Skovronsky, and M.J. Pontecorvo are employees of Avid, a division of Eli Lilly, and formerly held Avid stock or options. Go to Neurology.org for full disclosures. NR 31 TC 96 Z9 97 U1 3 U2 25 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 2012 VL 79 IS 16 BP 1636 EP 1644 DI 10.1212/WNL.0b013e3182661f74 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 022VL UT WOS:000309991800009 PM 22786606 ER PT J AU Hadzi, TC Hendricks, AE Latourelle, JC Lunetta, KL Cupples, LA Gillis, T Srinidhi, J Gusella, JF MacDonald, ME Myers, RH Vonsattel, JP AF Hadzi, Tiffany C. Hendricks, Audrey E. Latourelle, Jeanne C. Lunetta, Kathryn L. Cupples, L. Adrienne Gillis, Tammy Srinidhi, Jayalakshmi Gusella, James F. MacDonald, Marcy E. Myers, Richard H. Vonsattel, Jean-Paul TI Assessment of cortical and striatal involvement in 523 Huntington disease brains SO NEUROLOGY LA English DT Article ID GENE-EXPRESSION; CEREBRAL-CORTEX; WHITE-MATTER; DEGENERATION; NEURONS; ATROPHY; ONSET; AGE AB Objective: To evaluate the relationship of striatal involvement in Huntington disease (HD) to involvement in other brain regions, CAG repeat size, onset age, and other factors. Methods: We examined patterns of neuropathologic involvement in 664 HD brains submitted to the Harvard Brain Tissue Resource Center. Brains with concomitant Alzheimer or Parkinson changes (n = 82), more than 20% missing data (n = 46), incomplete sample submission (n = 12), or CAG repeat less than 36 (n = 1) were excluded, leaving 523 cases. Standardized ratings from 0 (absent) to 4 (severe) of gross and microscopic involvement were performed for 50 regions. Cluster analysis reduced the data to 2 main measures of involvement: striatal and cortical. Results: The clusters were correlated with each other (r = 0.42) and with disease duration (striatal: r = 0.35; cortical: r = 0.31). The striatal cluster was correlated with HD repeat size (r = 0.50). The cortical cluster showed a stronger correlation with decreased brain weight (r = -0.52) than the striatal cluster (r = -0.33). The striatal cluster was correlated with younger death age (r = -0.31) and onset age (r = -0.46) while the cortical cluster was not (r = 0.09, r = -0.04, respectively). Conclusions: The 2 brain clusters had different relationships to the HD CAG repeat size, onset age, and brain weight, suggesting that neuropathologic involvement does not proceed in a strictly coupled fashion. The pattern and extent of involvement varies substantially from one brain to the next. These results suggest that regional involvement in HD brain is modified by factors which, if identified, may lend insight into novel routes to therapeutics. Neurology (R) 2012; 79: 1708-1715 C1 [Hadzi, Tiffany C.; Latourelle, Jeanne C.; Myers, Richard H.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Hendricks, Audrey E.; Lunetta, Kathryn L.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Gillis, Tammy; Srinidhi, Jayalakshmi; Gusella, James F.; MacDonald, Marcy E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Vonsattel, Jean-Paul] Columbia Univ, Taub Inst Res Alzheimers Dis & Aging Brain, Dept Pathol & Cell Biol, Med Ctr, New York, NY USA. Columbia Univ, Coll Phys & Surg, New York Presbyterian Hosp, New York, NY USA. RP Myers, RH (reprint author), Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. EM rmyers@bu.edu RI Hendricks, Audrey/I-4127-2016; OI Hendricks, Audrey/0000-0002-7152-0287; Latourelle, Jeanne/0000-0002-4218-9572; Myers, Richard/0000-0002-8365-2674; Lunetta, Kathryn/0000-0002-9268-810X; Cupples, L. Adrienne/0000-0003-0273-7965 FU National Institutes of Health, National Institute of Neurological Disorders and Stroke (Huntington's Disease Center Without Walls) [P50-016367]; Jerry McDonald Huntington's Disease Research Fund; CHDI Foundation Inc.; Huntington's Disease Society of America's Coalition for the Cure; NIH; Howard Hughes Collaborative Innovative Award; RJG Foundation; Susan G. Komen for the Cure; Hereditary Disease Foundation; Parkinson's disease Foundation FX Supported by grants from the National Institutes of Health, National Institute of Neurological Disorders and Stroke (P50-016367, Huntington's Disease Center Without Walls), The Jerry McDonald Huntington's Disease Research Fund, the CHDI Foundation Inc., and the Huntington's Disease Society of America's Coalition for the Cure.; T. Hadzi is supported by the NIH, The Jerry McDonald Huntington's Disease Research Fund, and a Howard Hughes Collaborative Innovative Award. A. Hendricks was supported by the NIH. J. Latourelle is supported by the NIH, the RJG Foundation, and a Howard Hughes Collaborative Innovative Award. K. Lunetta is supported by the NIH. L. A. Cupples is supported by the NIH and the Susan G. Komen for the Cure. T. Gillis is supported by the NIH. J. Mysore is supported by the NIH. J. Gusella is supported by the NIH, the CHDI Foundation Inc., and the Huntington's Disease Society of America's Coalition for the Cure. M. MacDonald is supported by the NIH and the CHDI Foundation, Inc. R. Myers is supported by the NIH, The Jerry McDonald Huntington's Disease Research Fund, and a Howard Hughes Collaborative Innovative Award. J. Vonsattel is supported by the NIH, the Hereditary Disease Foundation, and the Parkinson's disease Foundation. Go to Neurology.org for full disclosures. NR 20 TC 20 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 2012 VL 79 IS 16 BP 1708 EP 1715 DI 10.1212/WNL.0b013e31826e9a5d PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 022VL UT WOS:000309991800018 PM 23035064 ER PT J AU Wise, SK Schlosser, RJ AF Wise, Sarah K. Schlosser, Rodney J. TI Evidence-Based Practice Sublingual Immunotherapy for Allergic Rhinitis SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article DE Sublingual immunotherapy; Allergic rhinitis; Allergy; Antigen; Allergen; Safety; Efficacy; Anaphylaxis ID INHALANT ALLERGY; FATAL REACTIONS; EFFICACY; SAFETY; RHINOCONJUNCTIVITIS; METAANALYSIS; ANTIBODIES; INJECTIONS; DIAGNOSIS; TABLETS AB In this article, the authors review the current evidence regarding the public health and economic impact of allergic rhinitis. Diagnostic methods for allergic disease are discussed as well as certain nuances of allergy skin testing protocols. In addition, the evidence supporting sublingual immunotherapy (SLIT) for allergic rhinitis is reviewed, with subsequent attention to certain subgroups, such as adults and children, seasonal versus perennial allergens, and SLIT efficacy for individual antigens. The authors consider the evidence supporting appropriate SLIT dosing as well as the existing data on SLIT safety. C1 [Schlosser, Rodney J.] Med Univ S Carolina, Charleston, SC 29425 USA. [Schlosser, Rodney J.] Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. [Wise, Sarah K.] Emory Univ, Atlanta, GA 30308 USA. RP Schlosser, RJ (reprint author), Med Univ S Carolina, 135 Rutledge Ave,MSC 550, Charleston, SC 29425 USA. EM schlossr@musc.edu NR 36 TC 2 Z9 2 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD OCT PY 2012 VL 45 IS 5 BP 1045 EP + DI 10.1016/j.otc.2012.06.008 PG 12 WC Otorhinolaryngology SC Otorhinolaryngology GA 020DG UT WOS:000309788300010 PM 22980684 ER PT J AU Berg, KM Lang, GR Salciccioli, JD Cocchi, MN Gautam, S Donnino, MW AF Berg, Katherine M. Lang, Gerald R. Salciccioli, Justin D. Cocchi, Michael N. Gautam, Shiva Donnino, Michael W. TI The Rapid Shallow Breathing Index as a Predictor of Failure of Noninvasive Ventilation for Patients With Acute Respiratory Failure SO RESPIRATORY CARE LA English DT Article DE noninvasive ventilation; NIV; respiratory failure; intubation ID POSITIVE-PRESSURE VENTILATION; OBSTRUCTIVE PULMONARY-DISEASE; MECHANICAL VENTILATION; ACUTE EXACERBATIONS; COPD; EXTUBATION; PNEUMONIA; SURVIVAL; SUCCESS; TRIAL AB BACKGROUND: Noninvasive ventilation (NIV) may reduce the need for intubation in acute respiratory failure (ARF). However, there is no standard method to predict success or failure with NIV. The rapid shallow breathing index (RSBI) is a validated tool for predicting readiness for extubation. We evaluated the ability of the RSBI to predict failure of NIV and mortality in ARF. METHODS: Prospective, observational trial of patients with ARF treated with NIV. NIV was initiated at the discretion of the clinicians, and an RSBI was recorded on the initial level of support (designated as assisted RSBI [aRSBI]). Patients were categorized by initial aRSBI value as either high (aRSBI > 105) or low (aRSBI <= 105). The primary end point was need for intubation, and the secondary end point was in-hospital mortality. Patients in the low and high aRSBI groups were compared using univariate analysis, followed by multivariable logistic regression to determine the association between aRSBI groups and outcome. RESULTS: A total of 101 patients were included. The majority of patients had an inspiratory pressure of 5-10 cm H2O in addition to an expiratory pressure of 5-8 cm H2O. Of 83 patients with an aRSBI <= 105, 26 (31%) required intubation, compared to 10/18 (55%) with an aRSBI > 105 (multivariate odds ratio 3.70, 95% CI 1.14-11.99, P = .03). When comparing mortality, 7/83 patients (8.4%) with an aRSBI <= 105 died, compared to 6/18 (33%) patients in the group with an aRSBI > 105 (multivariate odds ratio 4.51, 95% CI 1.19-17.11, P = .03). CONCLUSIONS: An aRSBI of > 105 is associated with need for intubation and increased in-hospital mortality. Whether patients with an elevated aRSBI could also have benefitted from an increase in NIV settings remains unclear. Validation of this concept in a larger patient population is warranted. C1 [Berg, Katherine M.] Beth Israel Deaconess Med Ctr, Dept Pulm & Crit Care, Boston, MA 02215 USA. [Lang, Gerald R.] Beth Israel Deaconess Med Ctr, Dept Resp Therapy, Boston, MA 02215 USA. [Cocchi, Michael N.] Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. [Cocchi, Michael N.] Beth Israel Deaconess Med Ctr, Dept Anesthesia & Crit Care, Boston, MA 02215 USA. [Gautam, Shiva] Beth Israel Deaconess Med Ctr, Clin Res Ctr, Boston, MA 02215 USA. [Donnino, Michael W.] Beth Israel Deaconess Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. [Donnino, Michael W.] Beth Israel Deaconess Med Ctr, Div Pulm & Crit Care, Boston, MA 02215 USA. RP Berg, KM (reprint author), Beth Israel Deaconess Med Ctr Pulm & Crit Care, 330 Brookline Ave,KB23, Boston, MA 02215 USA. EM kberg@bidmc.harvard.edu NR 21 TC 10 Z9 11 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD OCT PY 2012 VL 57 IS 10 BP 1548 EP 1554 DI 10.4187/respcare.01597 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 024NP UT WOS:000310116200002 PM 22417884 ER PT J AU Hess, DR AF Hess, Dean R. TI The Role of Noninvasive Ventilation in the Ventilator Discontinuation Process SO RESPIRATORY CARE LA English DT Article; Proceedings Paper CT New Horizons Symposium on Ventilator Liberation Process - A Fresh Look at the Evidence at the AARC Congress CY NOV 05-08, 2011 CL Tampa, FL SP AARC DE COPD; extubation; mechanical ventilation; noninvasive ventilation; spontaneous breathing trail; weaning ID POSITIVE-PRESSURE VENTILATION; RANDOMIZED CONTROLLED-TRIAL; ACUTE RESPIRATORY-FAILURE; INTENSIVE-CARE-UNIT; EXTUBATION FAILURE; MECHANICAL VENTILATION; PREVENTIVE USE; PATIENT; RISK; MASK AB In recent years, there has been increasing interest in the use of noninvasive ventilation (NIV) in the post-extubation period to shorten the length of invasive ventilation, to prevent extubation failure, and to rescue a failed extubation. The purpose of this review is to summarize the evidence related to the use of NIV in these settings. NIV can be used to allow earlier extubation in selected patients who do not successfully complete a spontaneous breathing trial (SBT). Its use in this setting should be restricted to patients who are intubated during an exacerbation of COPD or patients with neuromuscular disease. This category of patients should be good candidates for NIV and should be extubated directly to NIV. In patients who successfully complete an SBT, but are at risk for extubation failure, NIV can be used to prevent extubation failure. These patients should also be good candidates for NIV and should be extubated directly to NIV. NIV should be used cautiously in patients who successfully complete an SBT, but develop respiratory failure within 48 hours post-extubation. In this setting, NIV is indicated only in patients with hypercapnic respiratory failure. Reintubation should not be delayed if NIV is not immediately successful in reversing the post-extubation respiratory failure. Evidence does not support routine use of NIV post-extubation. C1 Harvard Univ, Massachusetts Gen Hosp, Resp Care Serv, Sch Med, Boston, MA 02114 USA. RP Hess, DR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Resp Care Serv, Sch Med, Ellison 401, Boston, MA 02114 USA. EM dhess@partners.org NR 41 TC 13 Z9 15 U1 1 U2 2 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD OCT PY 2012 VL 57 IS 10 BP 1619 EP 1625 DI 10.4187/respcare.01943 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 024NP UT WOS:000310116200011 PM 23013899 ER PT J AU Bittner, EA Schmidt, UH AF Bittner, Edward A. Schmidt, Ulrich H. TI The Ventilator Liberation Process: Update on Technique, Timing, and Termination of Tracheostomy SO RESPIRATORY CARE LA English DT Article; Proceedings Paper CT New Horizons Symposium on Ventilator Liberation Process - A Fresh Look at the Evidence at the AARC Congress CY NOV 05-08, 2011 CL Tampa, FL SP AARC DE tracheostomy; decannulation; intensive care ID PERCUTANEOUS DILATATIONAL TRACHEOSTOMY; PROLONGED MECHANICAL VENTILATION; CRITICALLY-ILL PATIENTS; INTENSIVE-CARE-UNIT; TRANSLARYNGEAL INTUBATION; DILATIONAL TRACHEOSTOMY; WARD MORTALITY; TRACHEOTOMY; METAANALYSIS; TRIAL AB Tracheostomy is one of the most commonly performed procedures in the ICU. Despite the frequency of the procedure, there remains controversy regarding selection of patients who should undergo tracheostomy, the optimal technique, timing of placement and decannulation, as well as impact on outcome associated with the procedure. A growing body of literature demonstrates that percutaneous tracheostomy performed in the ICU is a safe procedure, even in high risk patients. Advances in techniques, together with adjuncts to improve visualization, seem promising and likely to further improve the safety of the technique. Although there was initial enthusiasm in support of early tracheostomy to improve patient outcomes, repeated studies have been unable to produce robust benefits. The question of optimal timing and location of decannulation has not been answered, but there is some reassurance that in aggregate, across a variety of ICUs, patients do not appear to be harmed by transfer to ward with tracheostomy. Future research into techniques, timing, and termination of tracheostomy is warranted. C1 [Bittner, Edward A.; Schmidt, Ulrich H.] Harvard Univ, Massachusetts Gen Hosp, Surg Intens Care Unit, Dept Anesthesia Crit Care & Pain Med,Sch Med, Boston, MA 02114 USA. RP Schmidt, UH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Surg Intens Care Unit, Dept Anesthesia Crit Care & Pain Med,Sch Med, 55 Fruit Street,Gray 4, Boston, MA 02114 USA. EM uschmidt@partners.org NR 41 TC 7 Z9 8 U1 0 U2 6 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD OCT PY 2012 VL 57 IS 10 BP 1626 EP 1634 DI 10.4187/respcare.01914 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 024NP UT WOS:000310116200012 PM 23013900 ER PT J AU Bittner, EA Schmidt, UH AF Bittner, Edward A. Schmidt, Ulrich H. TI Tracheal Reintubation: Caused by "Too Much of a Good Thing"? SO RESPIRATORY CARE LA English DT Editorial Material ID INTENSIVE-CARE-UNIT; POSTEXTUBATION LARYNGEAL EDEMA; SPONTANEOUS BREATHING TRIAL; MECHANICAL VENTILATION; EXTUBATION FAILURE; WEANING FAILURE; OUTCOMES; PROTOCOL; ULTRASOUND; DECISION C1 [Bittner, Edward A.; Schmidt, Ulrich H.] Massachusetts Gen Hosp, Surg Intens Care Unit, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP Schmidt, UH (reprint author), Massachusetts Gen Hosp, Surg Intens Care Unit, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Gray 4, Boston, MA 02114 USA. EM uschmidt@partners.org NR 35 TC 2 Z9 3 U1 0 U2 1 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD OCT PY 2012 VL 57 IS 10 BP 1687 EP 1691 DI 10.4187/respcare.02082 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 024NP UT WOS:000310116200021 PM 23013905 ER PT J AU Hirn, C Toteberg-Harms, M Bauer, G Jaggi, G Zehnder, S Lindegger, D Funk, J AF Hirn, Cornelia Toeteberg-Harms, Marc Bauer, Gregor Jaggi, Gregor Zehnder, Simon Lindegger, Daniel Funk, Jens TI Selective laser trabeculoplasty in patients under maximum tolerated medical therapy: a retrospective analysis SO SPEKTRUM DER AUGENHEILKUNDE LA German DT Article DE Laser; Glaucoma; Intraocular pressure ID OPEN-ANGLE GLAUCOMA; RANDOMIZED CLINICAL-TRIAL; INTRAOCULAR-PRESSURE RESPONSE; OCULAR HYPERTENSION; OUTFLOW FACILITY; PROSTAGLANDIN; PHACOEMULSIFICATION; IMPLANTATION; REDUCTION; MECHANISM AB Reduction of intraocular pressure (IOP) is still the mainstay of glaucoma treatment. Aim of this retrospective study was to analyse the efficacy of selective laser trabeculoplasty (SLT) in patients under maximum tolerated medical therapy. Special attention was paid to the question whether specific preoperative factors may influence the outcome of SLT. Inclusion criteria were patients with ocular hypertension or open angle glaucoma (primary open angle glaucoma, pseudoexfoliative glaucoma, pigmentary glaucoma, and normal tension glaucoma) who underwent SLT between 3/2008 and 12/2010 due to uncontrolled IOP despite maximum tolerated medical therapy, with a follow-up of at least 3 months. Data were collected preoperatively and then 1 day, 1 month and then 3-monthly after SLT up to a maximum follow-up of 2.5 years. Main outcome measures were mean IOP reduction and success rates (A(3) 20 % IOP-reduction). Repeat SLT was not considered a failure. One hundred and thirty-one eyes of 98 patients (58 female, mean age 71.6 +/- 11.2 years, mean follow-up 1.05 +/- 0.67 years) were included in the analysis. Mean IOP pre SLT was 19.6 +/- 4.9 mmHg. Mean IOP was significantly reduced up to 1.75 years after SLT (16.6 +/- 3.6; p = 0.044). Up to 2 years of follow-up, patients with higher baseline IOP had greater reduction of IOP (R-2 = 0.358; p = 0.009). There was no significant difference in survival analysis for phakic vs. pseudophakic patients as well as for patients with vs. without Prostaglandins (p = 0.671 and p = 0.994, respectively). Twelve eyes had a repeated SLT (mean time to re-SLT 1.03 +/- 0.55 years). Fifteen eyes had additional IOP lowering surgery (mean time to failure 0.84 +/- 0.52 years). Even in patients on maximum IOP lowering medication SLT significantly reduces IOP for up to 1.75 years, although the effect declines in magnitude over the time. IOP reduction is greater in patients with higher preoperative IOP. C1 [Hirn, Cornelia; Toeteberg-Harms, Marc; Bauer, Gregor; Jaggi, Gregor; Zehnder, Simon; Lindegger, Daniel; Funk, Jens] Univ Spital Zurich, Augenklin, CH-8091 Zurich, Switzerland. [Hirn, Cornelia] Moorfields Eye Hosp NHS Fdn Trust, NIHR BRC, London EC1V 2PD, England. [Hirn, Cornelia] UCL Inst Ophthalmol, London EC1V 2PD, England. [Toeteberg-Harms, Marc] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Hirn, C (reprint author), Univ Spital Zurich, Augenklin, Frauenklin Str 24, CH-8091 Zurich, Switzerland. EM corneliahirn@aol.de RI Toteberg-Harms, Marc/J-4954-2013 OI Toteberg-Harms, Marc/0000-0002-2134-1336 NR 40 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0930-4282 J9 SPEKTRUM AUGENHEILKD JI Spektrum Augenheilkd. PD OCT PY 2012 VL 26 IS 4 BP 205 EP 211 DI 10.1007/s00717-012-0118-5 PG 7 WC Ophthalmology SC Ophthalmology GA 025EU UT WOS:000310169100005 ER PT J AU Eisner, BH Sheth, S Dretler, SP Herrick, B Pais, VM AF Eisner, Brian H. Sheth, Sonali Dretler, Stephen P. Herrick, Benjamin Pais, Vernon M., Jr. TI Abnormalities of 24-Hour Urine Composition in First-time and Recurrent Stone-formers SO UROLOGY LA English DT Article ID CALCIUM-OXALATE NEPHROLITHIASIS; POTASSIUM CITRATE; UROLITHIASIS; PROPHYLAXIS; PREVENTION; THIAZIDES AB OBJECTIVE To examine differences in 24-hour urine composition between recurrent and first-time stone-formers. METHODS A retrospective review of patients evaluated in 2 metabolic stone clinics was performed. Recurrent stone formation was defined as patients with a history of more than 1 stone episode and first-time stone-formers were those with a history of a single-stone episode. Frequencies of urine metabolic abnormalities were noted. Multivariate linear regression was performed to evaluate the likelihood of abnormalities of 24-hour urine composition. RESULTS Three-hundred eleven patients met inclusion criteria: 71 (22.8%) were first-time stone-formers and 240 (77.1%) were recurrent stone-formers. On univariate analysis, the likelihood of having a single abnormality of 24-hour urine composition (ie, hypercalciuria, hyperoxaluria, hyperuricosuria, or hypocitraturia) was similar between the 2 groups (83.1% for first-time vs 88.8% for recurrent, P = NS). In addition, there were similar rates of hypercalciuria (39.4% vs 43.3%, P = NS), hyperoxaluria (32.4% vs 33.3%, P = NS), hyperuricosuria (29.6% vs 23.3%, P = NS), and hypocitraturia (45.0% vs 45.0%, P = NS). On multivariate logistic regression, there was no difference in detection of any urine abnormality (ie, hypercalciuria or hyperoxaluria or hypocitraturia or hyperuricosuria) between first-time (referent) or recurrent stone-formers (OR 1.68, 95% CI .8-3.5, P = .2). CONCLUSION In this study, detection of urine abnormalities was similar in first-time and recurrent stone-formers. Given the strong patient preference for stone prevention and the high success of directed therapy in the literature, we believe it is not unreasonable to offer comprehensive metabolic evaluation to first-time stone-formers who express a desire to undergo evaluation. UROLOGY 80: 776-779, 2012. (c) 2012 Elsevier Inc. C1 [Eisner, Brian H.] Harvard Univ, Sch Med, Dept Urol, Massachusetts Gen Hosp, Boston, MA 02114 USA. Dartmouth Hitchcock Med Ctr, Dept Urol, Lebanon, NH 03766 USA. RP Eisner, BH (reprint author), Harvard Univ, Sch Med, Dept Urol, Massachusetts Gen Hosp, GRB 1102,55 Fruit St, Boston, MA 02114 USA. EM beisner@partners.org NR 26 TC 17 Z9 17 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD OCT PY 2012 VL 80 IS 4 BP 776 EP 779 DI 10.1016/j.urology.2012.06.034 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 016LB UT WOS:000309518700014 PM 22921696 ER PT J AU Eisner, BH Sheth, S Dretler, SP Herrick, B Pais, VM AF Eisner, Brian H. Sheth, Sonali Dretler, Stephen P. Herrick, Benjamin Pais, Vernon M., Jr. TI High Dietary Magnesium Intake Decreases Hyperoxaluria in Patients With Nephrolithiasis SO UROLOGY LA English DT Article ID CALCIUM-OXALATE NEPHROLITHIASIS; URINARY RISK-FACTORS; UROLITHIASIS; PREVENTION; EXCRETION; THERAPY; STONES; OXIDE AB OBJECTIVE To examine the relationship between urine magnesium and hyperoxaluria in a cohort of patients with recurrent stone formation. METHODS A total of 311 patients with nephrolithaisis were evaluated. The patients were divided into quintiles of urine magnesium excretion, an accepted surrogate of dietary magnesium intake. Multivariate analysis was used to examine the relationship between magnesium and hyperoxaluria. RESULTS The mean patient age was 50.0 +/- 14.9 years, the body mass index was 28.0 +/- 5.9 kg/m(2), and 130 were women and 181 were men. The mean urine magnesium excretion was 100.8 +/- 42.0 mg/d (range 17.8-224.8). On multivariate analysis, an increasing quintile of urine magnesium was associated with decreasing hyperoxaluria (beta = -0.37, 95% confidence interval -0.6 to -0.14, P < .05 for trend). When analyzed as separate quintiles with the lowest quintile of magnesium as the referent, only the greatest quintile demonstrated a statistically significant decrease in hyperoxaluria (beta = -1.7, 95% confidence interval -2.7 to -0.7, P < .05 for trend). CONCLUSION Increasing magnesium intake was associated with decreasing hyperoxaluria in this population of patients with stone formation. Our findings showed that high magnesium intake might be required to observe clinically significant effects from magnesium. UROLOGY 80: 780-783, 2012. (c) 2012 Elsevier Inc. C1 [Eisner, Brian H.] Harvard Univ, Sch Med, Dept Urol, Massachusetts Gen Hosp, Boston, MA 02114 USA. Dartmouth Hitchcock Med Ctr, Dept Urol, Lebanon, NH 03766 USA. RP Eisner, BH (reprint author), Harvard Univ, Sch Med, Dept Urol, Massachusetts Gen Hosp, GRB 1102,55 Fruit St, Boston, MA 02114 USA. EM beisner@partners.org NR 23 TC 3 Z9 3 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD OCT PY 2012 VL 80 IS 4 BP 780 EP 783 DI 10.1016/j.urology.2012.06.033 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 016LB UT WOS:000309518700015 PM 22921695 ER PT J AU Hopcia, K Dennerlein, JT Hashimoto, D Orechia, T Sorensen, G AF Hopcia, Karen Dennerlein, Jack Tigh Hashimoto, Dean Orechia, Terry Sorensen, Glorian TI Occupational Injuries for Consecutive and Cumulative Shifts Among Hospital Registered Nurses and Patient Care Associates SO WORKPLACE HEALTH & SAFETY LA English DT Article ID LONG WORKING HOURS; NIGHT SHIFTS; MUSCULOSKELETAL DISORDERS; CURRENT KNOWLEDGE; HEALTH; WORKERS; PERFORMANCE; SCHEDULES; IMPACTS; STRESS AB Nontraditional work shifts for hospital registered nurses and patient care associates and associated injuries were examined through a case-control study. Inpatient care requires that many staff work nontraditional shifts, including nights and 12-hour shifts, but some characteristics remain unexplored, especially consecutive shifts. A total of 502 cases (injured workers) were matched to single controls based on their hospital, unit type, job type, gender, and age (+/- 5 years). Conditional logistic regression was used for the analysis, controlling for weekly hours scheduled. For both, consecutive shifts of 2 or more days and some various cumulative shifts over a week and month period, especially night shifts, were associated with increased odds of injury. More investigations on the phenomenon of consecutive shifts are recommended. Additionally, the assessment of shift policy and subsequent injury outcomes is necessary before implementing intervention strategies. C1 [Hopcia, Karen] Univ Illinois, Coll Nursing, Occupat Hlth Nursing Program, Dept Hlth Syst Sci, Chicago, IL 60612 USA. [Dennerlein, Jack Tigh] Northeastern Univ, Bouve Coll Hlth Sci, Dept Phys Therapy, Boston, MA 02115 USA. [Sorensen, Glorian] Harvard Univ, Sch Publ Hlth, Soc Human Dev & Hlth, Cambridge, MA 02138 USA. [Sorensen, Glorian] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Hashimoto, Dean; Orechia, Terry] Partners Healthcare, Boston, MA USA. RP Hopcia, K (reprint author), Univ Illinois, Coll Nursing, Occupat Hlth Nursing Program, Dept Hlth Syst Sci, Hlth Syst Sci NURS 910,845 S Ashland Ave, Chicago, IL 60612 USA. EM khopcia@uic.edu FU National Institute for Occupational Safety and Health [U19 OH008861]; National Cancer Institute [K05 CA 108663] FX This work was supported by a grant from the National Institute for Occupational Safety and Health (U19 OH008861) and in part by a grant from the National Cancer Institute (K05 CA 108663) to Dr. Sorensen. NR 32 TC 10 Z9 10 U1 2 U2 11 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 2165-0799 J9 WORKPLACE HEALTH SAF JI Workplace Health Saf. PD OCT PY 2012 VL 60 IS 10 BP 437 EP 444 DI 10.3928/21650799-20120917-39 PG 8 WC Nursing SC Nursing GA 024FP UT WOS:000310095400005 PM 22998692 ER PT J AU Westen, D Malone, JC DeFife, JA AF Westen, Drew Malone, Johanna C. DeFife, Jared A. TI An empirically derived approach to the classification and diagnosis of mood disorders SO WORLD PSYCHIATRY LA English DT Article DE Mood disorders; suicidality; depression; dimensional diagnosis; prototype matching ID PERSONALITY DIAGNOSIS; CLINICAL-PRACTICE; MENTAL-DISORDERS; AXIS II; PROTOTYPE; COMORBIDITY; PSYCHOPATHOLOGY; DEPRESSION; SPECTRUM; ANXIETY AB This article describes a system for diagnosing mood disorders that is empirically derived and designed for its clinical utility in everyday practice. A random national sample of psychiatrists and clinical psychologists described a randomly selected current patient with a measure designed for clinically experienced informants, the Mood Disorder Diagnostic Questionnaire (MDDQ), and completed additional research forms. We applied factor analysis to the MDDQ to identify naturally occurring diagnostic groupings within the patient sample. The analysis yielded three clinically distinct mood disorder dimensions or spectra, consistent with the major mood disturbances included in the DSM and ICD over successive editions (major depression, dysthymia, and mania), along with a suicide risk index. Diagnostic criteria were determined strictly empirically. Initial data using diagnostic efficiency statistics supported the accuracy of the dimensions in discriminating DSM-IV diagnoses; regression analyses supported the discriminant validity of the MDDQ scales; and correlational analysis demonstrated coherent patterns of association with family history of mood disorders and functional outcomes, supporting validity. Perhaps most importantly, the MDDQ diagnostic scales demonstrated incremental validity in predicting adaptive functioning and psychiatric history over and above DSM-IV diagnosis. The empirically derived syndromes can be used to diagnose mood syndromes dimensionally without complex diagnostic algorithms or can be combined into diagnostic prototypes that eliminate the need for ever-expanding categories of mood disorders that are clinically unwieldy. C1 [Westen, Drew; DeFife, Jared A.] Emory Univ, Dept Psychiat & Psychol, Atlanta, GA 30322 USA. [Malone, Johanna C.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Malone, Johanna C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Westen, D (reprint author), Emory Univ, Dept Psychiat & Psychol, 36 Eagle Row, Atlanta, GA 30322 USA. FU National Institute of Mental Health [R01-MH62377, R01-MH78100] FX This research was supported by National Institute of Mental Health grants R01-MH62377 and R01-MH78100. NR 38 TC 8 Z9 11 U1 0 U2 5 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 1723-8617 J9 WORLD PSYCHIATRY JI World Psychiatry PD OCT PY 2012 VL 11 IS 3 BP 172 EP 180 PG 9 WC Psychiatry SC Psychiatry GA 018XF UT WOS:000309699800015 PM 23024677 ER PT J AU Mylopoulos, M Lohfeld, L Norman, GR Dhaliwal, G Eva, KW AF Mylopoulos, Maria Lohfeld, Lynne Norman, Geoffrey R. Dhaliwal, Gurpreet Eva, Kevin W. TI Renowned Physicians' Perceptions of Expert Diagnostic Practice SO ACADEMIC MEDICINE LA English DT Article AB Purpose To further the development of a substantive theory of expert diagnostic practice, the authors explored the ways in which exceptional physicians, nominated by their peers, conceptualized their own diagnostic expertise specifically and diagnostic excellence generally. Method In this grounded theory, interview-based study, physicians at six North American research sites were nominated by their peers as exceptional diagnosticians and exceptional professionals and invited to participate in the study. A saturation sample included 34 participants, 20 exceptional diagnosticians, and 14 exceptional professionals. Using a constant comparative approach, the authors conducted one-on-one interviews with participants, transcribed the audiotapes of those interviews, and analyzed them for emergent themes. They developed a stable thematic structure and applied it to the entire data set. Results Four interconnected themes emerged that inform the community's understanding of how physicians conceptualize expert diagnostic practice: (1) possession of extensive knowledge built through purposeful, continuous engagement in clinical practice, (2) possession of the skills to effectively gather patient stories, (3) reflective integration of that knowledge and those patient stories during diagnosis, and (4) continuous learning through clinical practice. Conclusions Exploring these results within the context of current discourses in medical education brings to the forefront two key features of physicians' construction of diagnostic excellence: (1) the integrated nature of the medical competencies that underpin the diagnostic process and (2) the optimally adaptive nature of the diagnostic process. These findings can inform the development of practical and effective pedagogical strategies to guide trainees, clinicians, and medical educators who strive for excellence. C1 [Mylopoulos, Maria] Univ Toronto, Fac Med, Toronto, ON, Canada. [Mylopoulos, Maria] Hosp Sick Children, Learning Inst, Toronto, ON M5G 1X8, Canada. [Lohfeld, Lynne; Norman, Geoffrey R.] McMaster Univ, Fac Hlth Sci, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. [Norman, Geoffrey R.] McMaster Univ, Fac Hlth Sci, Programme Educ Res & Dev, Hamilton, ON, Canada. [Dhaliwal, Gurpreet] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, San Francisco, CA USA. [Eva, Kevin W.] Univ British Columbia, Fac Med, Ctr Hlth Educ Scholarship, Vancouver, BC, Canada. [Eva, Kevin W.] Univ British Columbia, Fac Med, Dept Med, Vancouver, BC, Canada. RP Mylopoulos, M (reprint author), SickKids Learning Inst, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM maria.mylopoulos@utoronto.ca FU Social Sciences and Humanities Research Council FX This project was funded by a grant from the Social Sciences and Humanities Research Council. NR 13 TC 18 Z9 18 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD OCT PY 2012 VL 87 IS 10 BP 1413 EP 1417 DI 10.1097/ACM.0b013e31826735fc PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 016UC UT WOS:000309544000027 PM 22914510 ER PT J AU Jena, AB Arora, VM Hauer, KE Durning, S Borges, N Oriol, N Elnicki, DM Fagan, MJ Harrell, HE Torre, D Prochaska, M Meltzer, DO Reddy, S AF Jena, Anupam B. Arora, Vineet M. Hauer, Karen E. Durning, Steven Borges, Nicole Oriol, Nancy Elnicki, D. Michael Fagan, Mark J. Harrell, Heather E. Torre, Dario Prochaska, Meryl Meltzer, David O. Reddy, Shalini TI The Prevalence and Nature of Postinterview Communications Between Residency Programs and Applicants During the Match SO ACADEMIC MEDICINE LA English DT Article ID MEDICAL-STUDENTS; PROFESSIONALISM; RECRUITMENT; DIRECTORS; SELECTION; ETHICS AB Purpose To examine the frequency and nature of postinterview communications between programs and applicants during the National Resident Matching Program (NRMP) Main Residency Match. Method The authors surveyed senior medical students at seven U.S. medical schools about postinterview communications with residency programs during the 2010 Match and analyzed the data. Results The response rate was 68.2% (564/827). Among respondents, 86.4% reported communicating with residency programs. Most (59.9%) reported telling more than one program they would rank it highly; 1.1% reported telling more than one they would rank it first. Students reported that programs told them they would be "ranked to match" (34.6%), be "ranked highly" (52.8%), or "fit well" (76.2%). Almost one-fifth (18.6 %) reported feeling assured by a program that they would match there but did not despite ranking that program first; 23.4% reported altering their rank order list based on communications with programs. In multivariate analysis, applicants to more competitive specialties were less likely to report being told they would be "ranked to match" (relative risk [RR] 0.72, 95% confidence interval [CI] 0.52-0.99). Applicants were more likely to report being told that they would be "ranked to match" if they received honors in the specialty clerkship (RR 1.39, 95% CI 1.10-1.77) or were members of Alpha Omega Alpha (RR 1.72, 95% CI 1.37-2.17). Conclusions Reports of nonbinding communications with programs were frequent. Students should be advised to interpret any comments made by programs cautiously. Reported violations of the NRMP's Match Participation Agreement were uncommon. C1 [Jena, Anupam B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Jena, Anupam B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Arora, Vineet M.] Univ Chicago, Pritzker Sch Med, Internal Med Residency Program, Chicago, IL 60637 USA. [Hauer, Karen E.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Durning, Steven] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Borges, Nicole] Wright State Univ, Boonshoft Sch Med, Dayton, OH 45435 USA. [Borges, Nicole] Dept Community Hlth, Dayton, OH USA. [Elnicki, D. Michael] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Fagan, Mark J.] Brown Univ, Warren Alpert Sch Med, Providence, RI 02912 USA. [Harrell, Heather E.] Univ Florida, Coll Med, Gainesville, FL USA. [Torre, Dario] Drexel Univ, Sch Med, Internal Med Residency Program, Philadelphia, PA 19104 USA. [Prochaska, Meryl] Loyola Univ, Chicago Sch Law, Chicago, IL 60611 USA. [Prochaska, Meryl] Univ Chicago, Gen Internal Med Sect, Chicago, IL 60637 USA. [Meltzer, David O.] Univ Chicago, Pritzker Sch Med, Sect Hosp Med, Chicago, IL 60637 USA. RP Jena, AB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM jena.anupam@mgh.harvard.edu RI Meltzer, David/C-2926-2009; OI Meltzer, David/0000-0003-2790-7393; Arora, Vineet/0000-0002-4745-7599 FU Department of Medicine at the University of Chicago Pritzker School of Medicine; Accreditation Council of Graduate Medical Education FX This study was funded by the Department of Medicine at the University of Chicago Pritzker School of Medicine.; Dr. Arora reports receiving funding from the Accreditation Council of Graduate Medical Education. NR 25 TC 9 Z9 9 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD OCT PY 2012 VL 87 IS 10 BP 1434 EP 1442 DI 10.1097/ACM.0b013e31826772a6 PG 9 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 016UC UT WOS:000309544000032 PM 22914523 ER PT J AU Lehavot, K AF Lehavot, Keren TI Coping Strategies and Health in a National Sample of Sexual Minority Women SO AMERICAN JOURNAL OF ORTHOPSYCHIATRY LA English DT Article DE sexual minority women; lesbians; bisexual women; adaptive coping strategies; maladaptive coping strategies; depression; somatic symptoms; social support ID QUALITY-OF-LIFE; PERCEIVED SOCIAL SUPPORT; YOUNG AUSTRALIAN WOMEN; MENTAL-HEALTH; PSYCHOLOGICAL DISTRESS; PHYSICAL HEALTH; GAY MEN; SOCIOECONOMIC-STATUS; DEPRESSIVE SYMPTOMS; COLLEGE-STUDENTS AB Coping strategies have been shown to significantly influence mental and physical health among heterosexual and medically ill populations. These associations have not been thoroughly examined among sexual minority women, who are known to shoulder a high burden of disease. This study assesses the impact of adaptive and maladaptive coping on mental and physical health among 1,381 lesbian and bisexual women and examines the potential mediating role of maladaptive coping in explaining bisexual womens poorer health relative to lesbians. Participants completed a web-based survey that assessed demographic characteristics, social support, adaptive and maladaptive coping strategies, and mental and physical health. Maladaptive coping strategies, especially behavioral disengagement and self-blame, were significantly associated with mental and physical health. Coping was more strongly predictive of mental health than physical health, and maladaptive coping more strongly predictive of health outcomes than demographics, social support, and adaptive coping. Interactions between social support and coping were generally not significant. Additionally, bisexual women reported more adverse mental and physical health outcomes than lesbians, and maladaptive coping significantly mediated these relationships. Providers working with sexual minority women may wish to pay particular attention to maladaptive coping strategies, countering these with adaptive, empowerment-based interventions. C1 [Lehavot, Keren] Univ Washington, Dept Psychol, Seattle, WA 98195 USA. RP Lehavot, K (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM klehavot@uw.edu FU Centers for Disease Control Grant for Public Health Research Dissertation [R36 CD000996] FX The research on which this article is based was supported by Centers for Disease Control Grant for Public Health Research Dissertation (R36 CD000996) awarded to Keren Lehavot when she was a graduate student in the Department of Psychology, University of Washington. The author thanks Jane Simoni, her graduate school advisor. NR 85 TC 14 Z9 14 U1 4 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-9432 J9 AM J ORTHOPSYCHIAT JI Am. J. Orthopsychiatr. PD OCT PY 2012 VL 82 IS 4 BP 494 EP 504 DI 10.1111/j.1939-0025.2012.01178.x PG 11 WC Psychiatry; Social Work SC Psychiatry; Social Work GA 017MX UT WOS:000309595200005 PM 23039347 ER PT J AU Kontos, EZ Emmons, KM Puleo, E Viswanath, K AF Kontos, Emily Z. Emmons, Karen M. Puleo, Elaine Viswanath, K. TI Contribution of Communication Inequalities to Disparities in Human Papillomavirus Vaccine Awareness and Knowledge SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID PRESCRIPTION DRUG ADVERTISEMENTS; LARGE SOCIAL NETWORK; INFORMATION; HEALTH; HPV; ACCEPTABILITY; COMPLETION; INTENTION; LITERACY; PATIENT AB Objectives. We examined the association of Internet-related communication inequalities on human papillomavirus (HPV) vaccine awareness and infection knowledge. Methods. We drew data from National Cancer Institute's 2007 Health Information National Trends Survey (n = 7674). We estimated multivariable logistic regression models to assess Internet use and Internet health information seeking on HPV vaccine awareness and infection knowledge. Results. Non Internet users, compared with general Internet users, had significantly lower odds of being aware of the HPV vaccine (odds ratio [OR] = 0.42; 95% confidence interval [CI] = 0.34, 0.51) and knowing that HPV causes cervical cancer (OR = 0.70; 95% Cl = 0.52, 0.95). Among general health information seekers, non Internet seekers compared with Internet information seekers exhibit significantly lower odds of HPV vaccine awareness (OR = 0.59; 95% CI = 0.46, 0.75), and of knowing about the link between HPV infection and cervical cancer (OR = 0.79; 95% CI = 0.63, 0.99) and the sexual transmission of HPV (OR = 0.71; 95% Cl = 0.57, 0.89). Among cancer information seekers, there were no differences in outcomes between Internet seekers and non Internet seekers. Conclusions. Use of a communication channel, such as the Internet, whose use is already socially and racially patterned, may widen observed disparities in vaccine completion rates. (Am J Public Health. 2012;102:1911-1920. doi:10.2105/AJPH.2011.300435) C1 [Kontos, Emily Z.; Emmons, Karen M.; Viswanath, K.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02215 USA. [Emmons, Karen M.; Viswanath, K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Puleo, Elaine] Univ Massachusetts, Amherst Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. RP Kontos, EZ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, 401 Pk Dr,Room 403F, Boston, MA 02215 USA. EM ekontos@hsph.harvard.edu FU US National Cancer Institute [5R01CA122894]; Harvard Education Program in Cancer Prevention and Control [5R25CA057711] FX This study was made possible with funding from the US National Cancer Institute through the following mechanisms: Click to Connect: Improving Health Literacy Through Computer Literacy (grant 5R01CA122894) and the Harvard Education Program in Cancer Prevention and Control (grant 5R25CA057711). NR 46 TC 24 Z9 25 U1 2 U2 17 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD OCT PY 2012 VL 102 IS 10 BP 1911 EP 1920 DI 10.2105/AJPH.2011.300435 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 015GU UT WOS:000309435200019 PM 22970692 ER PT J AU Wright, S Armeson, K Hill, EG Streck, C Leddy, L Cole, D Esnaola, N Camp, ER AF Wright, Sharee Armeson, Kent Hill, Elizabeth G. Streck, Christian Leddy, Lee Cole, David Esnaola, Nestor Camp, E. Ramsay TI The role of sentinel lymph node biopsy in select sarcoma patients: a meta-analysis SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Sarcoma; Sentinel; Lymph node ID CLEAR-CELL SARCOMA; SOFT-TISSUE SARCOMA; EXTREMITY RHABDOMYOSARCOMA; PEDIATRIC-PATIENTS; MELANOMA; METASTASIS; EXPERIENCE; MANAGEMENT; CANCER; ADULTS AB BACKGROUND: Sentinel lymph node (SLN) biopsy is a staging technique for occult lymph node disease. SLN biopsy has been applied to select patients with sarcoma, although the clinical utility remains uncertain. METHODS: A PubMed/MEDLINE literature search was performed, and SLN biopsy outcomes were analyzed using a Bayesian meta-analytic approach to obtain point and interval estimates of rates of interest. RESULTS: Sixteen studies involving SLN biopsy in patients with sarcoma were identified. Of 114 patients reported, 14 patients had positive SLNs (crude estimate, 12%; meta-analysis estimate, 17%). The meta-analysis false-negative rate was 29% (95% credible interval, 5%-59%). Recurrence and death rates in the SLN-positive group were higher than in the SLN-negative group. CONCLUSIONS: This investigation highlights the current role of SLN biopsy in select patients with sarcoma for tumor staging. Questions regarding the high false-negative rate and management of micrometastatic lymphatic disease in patients with sarcoma still exist. (C) 2012 Elsevier Inc. All rights reserved. C1 [Camp, E. Ramsay] Med Univ S Carolina, Dept Surg, Div Surg Oncol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Camp, ER (reprint author), Med Univ S Carolina, Dept Surg, Div Surg Oncol, Charleston, SC 29425 USA. EM campe@musc.edu NR 31 TC 7 Z9 7 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD OCT PY 2012 VL 204 IS 4 BP 428 EP 433 DI 10.1016/j.amjsurg.2011.12.019 PG 6 WC Surgery SC Surgery GA 020JT UT WOS:000309805500004 PM 22578407 ER PT J AU Attwood, BH Liteplo, AS Noble, VE AF Attwood, B. H. Liteplo, A. S. Noble, V. E. TI Emerging Image Transfer Technology for Portable Ultrasonography SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 08-09, 2012 CL Denver, CO SP Amer Coll Emergency Phys (ACEP) C1 [Attwood, B. H.] John Radcliffe Hosp, Oxford OX3 9DU, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2012 VL 60 IS 4 SU S BP S144 EP S145 PG 2 WC Emergency Medicine SC Emergency Medicine GA 018BX UT WOS:000309636100406 ER PT J AU Dalziel, P Liteplo, AS Noble, VE AF Dalziel, P. Liteplo, A. S. Noble, V. E. TI Impact of a Point of Care Emergency Ultrasonography Program on Consultative Echocardiography Ordering SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 08-09, 2012 CL Denver, CO SP Amer Coll Emergency Phys (ACEP) C1 [Dalziel, P.; Liteplo, A. S.; Noble, V. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2012 VL 60 IS 4 SU S BP S144 EP S144 PG 1 WC Emergency Medicine SC Emergency Medicine GA 018BX UT WOS:000309636100405 ER PT J AU Elmer, J Hou, P Wilcox, SR Chang, Y Bajwa, E Hess, D Camargo, CA Greenberg, SM Rosand, J Pallin, DJ Goldstein, JN AF Elmer, J. Hou, P. Wilcox, S. R. Chang, Y. Bajwa, E. Hess, D. Camargo, C. A., Jr. Greenberg, S. M. Rosand, J. Pallin, D. J. Goldstein, J. N. TI Risk of Acute Lung Injury After Spontaneous Intracerebral Hemorrhage SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 08-09, 2012 CL Denver, CO SP Amer Coll Emergency Phys (ACEP) C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RI Pallin, Daniel/H-6382-2013; Goldstein, Joshua/H-8953-2016 OI Pallin, Daniel/0000-0002-8517-9702; NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2012 VL 60 IS 4 SU S BP S19 EP S19 PG 1 WC Emergency Medicine SC Emergency Medicine GA 018BX UT WOS:000309636100048 ER PT J AU Gabayan, GZ Asch, SM Sun, BC AF Gabayan, G. Z. Asch, S. M. Sun, B. C. TI Short-Term Readmission Following Discharge From California Emergency Departments SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 08-09, 2012 CL Denver, CO SP Amer Coll Emergency Phys (ACEP) C1 [Gabayan, G. Z.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Gabayan, G. Z.] W Los Angeles VA, Los Angeles, CA USA. Vet Affairs Palo Alto Hlth Ctr, Palo Alto, CA USA. Oregon Hlth & Sci Univ, Portland, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2012 VL 60 IS 4 SU S BP S73 EP S74 PG 2 WC Emergency Medicine SC Emergency Medicine GA 018BX UT WOS:000309636100203 ER PT J AU Gabayan, GZ Sun, BC Asch, SM Timmermans, S Hoffman, JR Derose, SF AF Gabayan, G. Z. Sun, B. C. Asch, S. M. Timmermans, S. Hoffman, J. R. Derose, S. F. TI A Qualitative Analysis of the Factors Associated With Unanticipated Short-Term Death Following Emergency Department Discharge SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 08-09, 2012 CL Denver, CO SP Amer Coll Emergency Phys (ACEP) C1 [Gabayan, G. Z.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Gabayan, G. Z.] W Los Angeles VA, Los Angeles, CA USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. Univ So Calif, Los Angeles, CA USA. Kaiser Permanente So Calif, Pasadena, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2012 VL 60 IS 4 SU S BP S74 EP S74 PG 1 WC Emergency Medicine SC Emergency Medicine GA 018BX UT WOS:000309636100204 ER PT J AU Gross, EA Clark, T Doherty, J Freeman, W Hansoti, B Ramoska, E Weaver, K Takayesu, K AF Gross, E. A. Clark, T. Doherty, J. Freeman, W. Hansoti, B. Ramoska, E. Weaver, K. Takayesu, K. TI Presence of Burnout Among Emergency Medicine Residents SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 08-09, 2012 CL Denver, CO SP Amer Coll Emergency Phys (ACEP) C1 [Gross, E. A.] Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. So Illinois Univ, Sch Med, Springfield, IL USA. Ohio Valley Med Ctr, Springfield, OH USA. Louisiana State Univ, Sch Med, New Orleans, LA USA. Univ Chicago, Chicago, IL 60637 USA. Drexel Univ, Sch Med, Philadelphia, PA 19104 USA. Lehigh Valley Hosp, Allentown, PA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2012 VL 60 IS 4 SU S BP S127 EP S127 PG 1 WC Emergency Medicine SC Emergency Medicine GA 018BX UT WOS:000309636100354 ER PT J AU Kabrhel, C Okechukwu, I Hariharan, P Takayesu, JK Temin, E Chang, Y AF Kabrhel, C. Okechukwu, I Hariharan, P. Takayesu, J. K. Temin, E. Chang, Y. TI The Incidence of Clinical Deterioration in Patients Diagnosed With Pulmonary Embolism: Results from the Safe Pulmonary Embolism Emergency Department Discharge Study SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 08-09, 2012 CL Denver, CO SP Amer Coll Emergency Phys (ACEP) C1 [Kabrhel, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2012 VL 60 IS 4 SU S BP S65 EP S65 PG 1 WC Emergency Medicine SC Emergency Medicine GA 018BX UT WOS:000309636100179 ER PT J AU Liu, SW Nagumey, JT Chang, Y Smulowitz, PB Parry, BA Eatherson, D Yelibi, C Atlas, SJ AF Liu, S. W. Nagumey, J. T. Chang, Y. Smulowitz, P. B. Parry, B. A. Eatherson, D. Yelibi, C. Atlas, S. J. TI Frequent Users of the Emergency Department: Do They Make Visits That Can Be Addressed in a Primary Care Setting? SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 08-09, 2012 CL Denver, CO SP Amer Coll Emergency Phys (ACEP) C1 [Liu, S. W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 1 Z9 1 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2012 VL 60 IS 4 SU S BP S155 EP S155 PG 1 WC Emergency Medicine SC Emergency Medicine GA 018BX UT WOS:000309636100435 ER PT J AU Pallin, DJ Allen, MB Binder, WD Filbin, MR Parmar, S Hooper, DC Camargo, CA AF Pallin, D. J. Allen, M. B. Binder, W. D. Filbin, M. R. Parmar, S. Hooper, D. C. Camargo, Jr C. A. TI Randomized, Double-blind, Placebo-controlled Trial of Trimethoprim-sulfamethoxazole Added to Cephalexin for Treatment of Cellulitis in the Age of CA-MRSA SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 08-09, 2012 CL Denver, CO SP Amer Coll Emergency Phys (ACEP) C1 [Pallin, D. J.] Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Pallin, Daniel/H-6382-2013 OI Pallin, Daniel/0000-0002-8517-9702 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2012 VL 60 IS 4 SU S BP S45 EP S46 PG 2 WC Emergency Medicine SC Emergency Medicine GA 018BX UT WOS:000309636100124 ER PT J AU Refaai, MA Goldstein, JN Milling, TJ Foehl, H Hug, B Sarode, R AF Refaai, M. A. Goldstein, J. N. Milling, T. J. Foehl, H. Hug, B. Sarode, R. TI Correction of INR and Coagulation Factor Levels in a Randomized Clinical Trial of Four-Factor Prothrombin Complex Concentrate (PCC-4) Versus Plasma for Urgent Vitamin K Antagonist Reversal SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 08-09, 2012 CL Denver, CO SP Amer Coll Emergency Phys (ACEP) C1 Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Med Ctr Brackenridge, Austin, TX USA. CSL Behring, King Of Prussia, PA USA. UT SW Med Ctr, Dallas, TX USA. RI Goldstein, Joshua/H-8953-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2012 VL 60 IS 4 SU S BP S10 EP S10 PG 1 WC Emergency Medicine SC Emergency Medicine GA 018BX UT WOS:000309636100025 ER PT J AU Rogg, J Rubin, JT Hansen, P Liu, S AF Rogg, J. Rubin, J. T. Hansen, P. Liu, S. TI The Frequency and Cost of Redundant Laboratory Testing for Transferred Emergency Department Patients SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 08-09, 2012 CL Denver, CO SP Amer Coll Emergency Phys (ACEP) C1 Harvard Affiliated Emergency Med Residency, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2012 VL 60 IS 4 SU S BP S13 EP S13 PG 1 WC Emergency Medicine SC Emergency Medicine GA 018BX UT WOS:000309636100032 ER PT J AU Runde, D He, C Rolston, D Psomadakis, C Harsouni, I Godbout, B Lee, J Shah, K Wiener, D Quaas, J AF Runde, D. He, C. Rolston, D. Psomadakis, C. Harsouni, I Godbout, B. Lee, J. Shah, K. Wiener, D. Quaas, J. TI Utilization Rates and Diagnostic Yield of Chest Computed Tomography Angiography in an Urban Emergency Department SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 08-09, 2012 CL Denver, CO SP Amer Coll Emergency Phys (ACEP) C1 [Runde, D.] Columbia Univ, St Lukes Roosevelt Hosp Ctr, New York, NY USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mt Sinai Hosp, New York, NY 10029 USA. Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2012 VL 60 IS 4 SU S BP S60 EP S61 PG 2 WC Emergency Medicine SC Emergency Medicine GA 018BX UT WOS:000309636100166 ER PT J AU Schuur, JD Carney, DP Berner, AR Benzer, TI Larson, RE Lyn, ET Michael, JA Raja, AS Ross, NG Venkatesh, AK AF Schuur, J. D. Carney, D. P. Berner, A. R. Benzer, T., I Larson, R. E. Lyn, E. T. Michael, J. A. Raja, A. S. Ross, N. G. Venkatesh, A. K. TI A "Top Five" List for Emergency Medicine: A Pilot to Improve the Value of Emergency Care SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 08-09, 2012 CL Denver, CO SP Amer Coll Emergency Phys (ACEP) C1 Brigham & Womens Hosp, Boston, MA 02115 USA. [Carney, D. P.] Harvard Univ, Sch Med, Boston, MA USA. Newton Wellesley Hosp, Newton, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Faulkner Hosp, Jamaica Plain, MA USA. N Shore Med Ctr, Salem, MA USA. Harvard Affiliated Emergency Med Residency, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2012 VL 60 IS 4 SU S BP S74 EP S75 PG 2 WC Emergency Medicine SC Emergency Medicine GA 018BX UT WOS:000309636100206 ER PT J AU Schuur, JD Hou, PC Pallin, DJ Yokoe, DS Espinola, JA Camargo, CA AF Schuur, J. D. Hou, P. C. Pallin, D. J. Yokoe, D. S. Espinola, J. A. Camargo, C. A., Jr. TI Central Venous Catheter Infection Practices in US Emergency Departments and Intensive Care Units, 2011 SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 08-09, 2012 CL Denver, CO SP Amer Coll Emergency Phys (ACEP) C1 [Schuur, J. D.] Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Emergency Med Network, Boston, MA 02114 USA. RI Pallin, Daniel/H-6382-2013 OI Pallin, Daniel/0000-0002-8517-9702 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2012 VL 60 IS 4 SU S BP S48 EP S48 PG 1 WC Emergency Medicine SC Emergency Medicine GA 018BX UT WOS:000309636100130 ER PT J AU Sheng, A Liu, X Kaufman, DA Bajwa, EK Esper, AM Gentile, NT Gong, MN Malhotra, A Frendl, G Hou, PC AF Sheng, A. Liu, X. Kaufman, D. A. Bajwa, E. K. Esper, A. M. Gentile, N. T. Gong, M. N. Malhotra, A. Frendl, G. Hou, P. C. CA Lung Injury Prevention Study Inve TI Is Initial Glucose Level a Predictor of Hospital Mortality in Patients Presenting With Sepsis to the Emergency Department? SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 08-09, 2012 CL Denver, CO SP Amer Coll Emergency Phys (ACEP) C1 Brigham & Womens Hosp, United States Crit Illness & Injury Trial Gr, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Bridgeport Hosp, Bridgeport, CT USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Emory Univ, Sch Med, Atlanta, GA USA. Temple Univ, Sch Med, Philadelphia, PA 19122 USA. Montefiore Med Ctr, Bronx, NY 10467 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2012 VL 60 IS 4 SU S BP S19 EP S20 PG 2 WC Emergency Medicine SC Emergency Medicine GA 018BX UT WOS:000309636100049 ER PT J AU Venkatesh, AK Curley, D Danh, ST Hansen, P Rubin, JT Parry, B Liu, S AF Venkatesh, A. K. Curley, D. Danh, S. T. Hansen, P. Rubin, J. T. Parry, B. Liu, S. TI Effectiveness of Communicating Vital Signs at Emergency Department Handoffs SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 08-09, 2012 CL Denver, CO SP Amer Coll Emergency Phys (ACEP) C1 Massachusetts Gen Hosp, Brigham & Womens Hosp, Harvard Affiliated Emergency Med Residency, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2012 VL 60 IS 4 SU S BP S49 EP S50 PG 2 WC Emergency Medicine SC Emergency Medicine GA 018BX UT WOS:000309636100135 ER PT J AU Wen, LS Gurrola, ER Kosowsky, JM Camargo, CA AF Wen, L. S. Gurrola, E. R. Kosowsky, J. M. Camargo, Jr C. A. TI The Provision of Diagnosis at Emergency Department Discharge: A Pilot Study SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 08-09, 2012 CL Denver, CO SP Amer Coll Emergency Phys (ACEP) C1 [Wen, L. S.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Harvard Affiliated Emergency Med Residency, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2012 VL 60 IS 4 SU S BP S88 EP S88 PG 1 WC Emergency Medicine SC Emergency Medicine GA 018BX UT WOS:000309636100241 ER PT J AU Yiadom, MY Hopkins, JB Imperato, J Sanchez, L Fisher, J Pearlmutter, M Kosowsky, JM White, B Perumalsamy, P Aljahawry, N Marill, K AF Yiadom, M. Y. Hopkins, J. B. Imperato, J. Sanchez, L. Fisher, J. Pearlmutter, M. Kosowsky, J. M. White, B. Perumalsamy, P. Aljahawry, N. Marill, K. TI Variability in Patient Care Process Measures Across 7 Massachusetts Academic Emergency Departments SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 08-09, 2012 CL Denver, CO SP Amer Coll Emergency Phys (ACEP) C1 [Yiadom, M. Y.] Cooper Univ Hosp, Camden, NJ USA. Milford Reg Hosp, Milford, MA USA. Mt Auburn Hosp, Cambridge, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. St Elizabeths Med Ctr, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Camden, NJ 08103 USA. RI Sanchez, Leon/H-5166-2012 OI Sanchez, Leon/0000-0002-8807-0913 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2012 VL 60 IS 4 SU S BP S114 EP S114 PG 1 WC Emergency Medicine SC Emergency Medicine GA 018BX UT WOS:000309636100316 ER PT J AU Yokell, MA Camargo, CA Wang, N Delgado, M AF Yokell, M. A. Camargo, Jr C. A. Wang, N. Delgado, M. TI Characteristics Associated With Routine Use of Alcohol Screening in United States Emergency Departments SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians (ACEP) CY OCT 08-09, 2012 CL Denver, CO SP Amer Coll Emergency Phys (ACEP) C1 [Yokell, M. A.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2012 VL 60 IS 4 SU S BP S134 EP S135 PG 2 WC Emergency Medicine SC Emergency Medicine GA 018BX UT WOS:000309636100378 ER PT J AU Yokell, DL Leece, AK Lebedev, A Miraghaie, R Ball, CE Zhang, JZ Kolb, H Elizarov, A Mahmood, U AF Yokell, Daniel L. Leece, Alicia K. Lebedev, Artem Miraghaie, Reza Ball, Carroll E. Zhang, Jianzhong Kolb, Hartmuth Elizarov, Arkadij Mahmood, Umar TI Microfluidic single vessel production of hypoxia tracer 1H-1-(3-[F-18]-fluoro-2-hydroxy-propyl)-2-nitro-imidazole ([F-18]-FMISO) SO APPLIED RADIATION AND ISOTOPES LA English DT Article DE FMISO; Microfluidic; PET ID FLUOROMISONIDAZOLE AB We report an automated synthesis of [F-18]-FMISO utilizing a prototype microfluidic radiochemistry module. The instrument allows for production of the tracer with 58% +/- 2% (11 runs) decay corrected yield. Total time of production, including synthesis and purification averages 60 min. Use of the microfluidic platform results in a specific activity of 138.6 GBq/mu mol, which is higher than previously reported for conventional reactors. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Yokell, Daniel L.; Leece, Alicia K.; Mahmood, Umar] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Lebedev, Artem; Miraghaie, Reza; Ball, Carroll E.; Zhang, Jianzhong; Kolb, Hartmuth; Elizarov, Arkadij] Siemens Med Solut Inc, Mol Imaging Biomarker Res, Culver City, CA 90230 USA. RP Yokell, DL (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, 55 Fruit St, Boston, MA 02114 USA. EM dyokell@partners.org OI Lebedev, Artem/0000-0001-5366-9793 FU NCI NIH HHS [U01 CA143056, U01 CA084301] NR 7 TC 11 Z9 11 U1 1 U2 21 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0969-8043 J9 APPL RADIAT ISOTOPES JI Appl. Radiat. Isot. PD OCT PY 2012 VL 70 IS 10 BP 2313 EP 2316 DI 10.1016/j.apradiso.2012.05.022 PG 4 WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Chemistry; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 017VT UT WOS:000309620000007 PM 22871433 ER PT J AU Maturo, S Hill, C Bunting, G Ballif, C Maurer, R Hartnick, C AF Maturo, Stephen Hill, Courtney Bunting, Glenn Ballif, Cathy Maurer, Rie Hartnick, Christopher TI Establishment of a Normative Pediatric Acoustic Database SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID QUALITY-OF-LIFE; HUMAN VOCAL FOLD; LAMINA PROPRIA; FUNDAMENTAL-FREQUENCY; VOICE; CHILDREN; AGE; MATURATION; DISORDERS; SPEECH AB Objectives: To establish a normative pediatric acoustic database and to analyze the acoustic characteristics of the age groups studied. Design: Prospective gathering of acoustic parameters on healthy children aged 4 to 18 years. Setting: An outpatient pediatric otolaryngology clinic. Patients: A total of 335 children (165 girls and 170 boys) were evaluated. Main Outcome Measures: Normative values were obtained for the acoustic parameters studied. Results: Discrete fundamental frequency changes occurred at ages 11 and 14 years in girls and ages 12 and 16 years in boys. Values for jitter percentage, shimmer percentage, and noise to harmonic ratio fell within the normative thresholds of adult values. Conclusions: This is the largest pediatric computerized voice analysis database in the English language. This database has been designed to develop an age-and sex-based growth chart to track the developing pediatric voice as it changes with maturation. A distinct vocal profile of girls and boys is evident, with key changes noted at critical periods of development and with significant differences among fundamental frequency between and within sexes. A comprehensive database can be used to help aid future voice therapy and phonosurgical strategies and provide the foundation for future studies into the development of the pediatric voice as it matures into adulthood. C1 [Hill, Courtney; Hartnick, Christopher] Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Bunting, Glenn; Ballif, Cathy] Harvard Univ, Sch Med, Voice & Speech Lab, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Maturo, Stephen] San Antonio Mil Med Ctr, Dept Otolaryngol, San Antonio, TX USA. [Maturo, Stephen] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Maurer, Rie] Brigham & Womens Hosp, Ctr Clin Invest, Boston, MA 02115 USA. [Maurer, Rie] Harvard Catalyst, Boston, MA USA. RP Hartnick, C (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Christopher_Hartnick@meei.harvard.edu NR 25 TC 14 Z9 14 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD OCT PY 2012 VL 138 IS 10 BP 956 EP 961 DI 10.1001/2013.jamaoto.104 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 021WR UT WOS:000309916600012 PM 22986573 ER PT J AU Lewin-Smith, M Kalasinsky, V Shilo, K Tomashefski, J Cropp, A AF Lewin-Smith, Michael Kalasinsky, Victor Shilo, Konstantin Tomashefski, Joseph Cropp, Alan TI Detection of Silicone in Lung Tissue SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Letter C1 [Lewin-Smith, Michael] Joint Pathol Ctr, Silver Spring, MD 20910 USA. [Kalasinsky, Victor] US Dept Vet Affairs, Vet Hlth Adm, Off Res & Dev, Washington, DC 20420 USA. [Shilo, Konstantin] Ohio State Univ, Med Ctr, Dept Pathol, Columbus, OH 43210 USA. [Tomashefski, Joseph] Case Western Reserve Univ, Sch Med, Dept Pathol, MetroHlth Med Ctr, Cleveland, OH 44109 USA. [Cropp, Alan] Pulm Med Consultants, Youngstown, OH 44512 USA. RP Lewin-Smith, M (reprint author), Joint Pathol Ctr, Silver Spring, MD 20910 USA. RI Shilo, Konstantin/E-4084-2011; OI S, K/0000-0002-6702-3130 NR 5 TC 2 Z9 2 U1 0 U2 0 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD OCT PY 2012 VL 136 IS 10 BP 1179 EP 1180 DI 10.5858/arpa.2012-0143-LE PG 2 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 020PH UT WOS:000309824900001 PM 23020716 ER PT J AU Hariri, LP Kradin, RL AF Hariri, Lida P. Kradin, Richard L. TI Detection of Silicone in Lung Tissue Reply SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Letter C1 [Hariri, Lida P.; Kradin, Richard L.] Massachusetts Gen Hosp, Dept Med, Dept Pathol, Boston, MA 02114 USA. RP Hariri, LP (reprint author), Massachusetts Gen Hosp, Dept Med, Dept Pathol, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD OCT PY 2012 VL 136 IS 10 BP 1180 EP 1180 DI 10.5858/arpa.2012-0268-LE PG 1 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 020PH UT WOS:000309824900002 ER PT J AU Oxnard, GR AF Oxnard, Geoffrey R. TI Strategies for Overcoming Acquired Resistance to Epidermal Growth Factor Receptor-Targeted Therapies in Lung Cancer SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article; Proceedings Paper CT Houston Lung Symposium CY APR 28-29, 2012 CL Houston, TX SP Methodist Hosp, Dept Pathol & Genom Medi, Houston Soc Clin Pathologists (HSCP) ID TYROSINE KINASE INHIBITOR; EGFR; GEFITINIB; ERLOTINIB; MUTATION; T790M; TRIAL; ADENOCARCINOMAS; CHEMOTHERAPY; PIK3CA AB Acquired resistance to targeted therapy in epidermal growth factor receptor (EGFR)-mutant lung cancer represents a valuable model for considering strategies of overcoming different types of cellular resistance mechanisms. Using existing data on resistance in EGFR-mutant lung cancer, this review will discuss 3 basic approaches for overcoming resistance to EGFR-targeted therapies: intensification of EGFR inhibition, combination of EGFR inhibitors with other targeted therapies, and changing to anticancer therapies acting via alternate pathways. (Arch Pathol Lab Med. 2012; 136: 1205-1209; doi: 10.5858/arpa.2012-0254-RA) C1 [Oxnard, Geoffrey R.] Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol,Dept Med Oncol, Boston, MA 02215 USA. [Oxnard, Geoffrey R.] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Oxnard, GR (reprint author), Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol,Dept Med Oncol, Boston, MA 02215 USA. EM Geoffrey_Oxnard@DFCI.harvard.edu NR 24 TC 12 Z9 15 U1 0 U2 0 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 EI 1543-2165 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD OCT PY 2012 VL 136 IS 10 BP 1205 EP 1209 DI 10.5858/arpa.2012-0254-RA PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 020PH UT WOS:000309824900010 PM 23020725 ER PT J AU Darragh, TM Colgan, TJ Cox, JT Heller, DS Henry, MR Luff, RD McCalmont, T Nayar, R Palefsky, JM Stoler, MH Wilkinson, EJ Zaino, RJ Wilbur, DC AF Darragh, Teresa M. Colgan, Terence J. Cox, J. Thomas Heller, Debra S. Henry, Michael R. Luff, Ronald D. McCalmont, Timothy Nayar, Ritu Palefsky, Joel M. Stoler, Mark H. Wilkinson, Edward J. Zaino, Richard J. Wilbur, David C. CA LAST Project Work Grp TI The Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions: Background and Consensus Recommendations from the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article DE squamous intraepithelial lesion; human papillomavirus; superficially invasive carcinoma; p16; terminology ID VULVAR INTRAEPITHELIAL NEOPLASIA; HUMAN-PAPILLOMAVIRUS INFECTION; RISK HUMAN-PAPILLOMAVIRUS; STAGE-IA CARCINOMA; SUPERFICIALLY INVASIVE-CARCINOMA; IMPROVES INTEROBSERVER AGREEMENT; DIAGNOSTIC SURGICAL PATHOLOGY; BETHESDA SYSTEM TERMINOLOGY; ADENOCARCINOMA IN-SITU; CELL CARCINOMA AB The terminology for human papillomavirus (HPV)-associated squamous lesions of the lower anogenital tract has a long history marked by disparate diagnostic terms derived from multiple specialties. It often does not reflect current knowledge of HPV biology and pathogenesis. A consensus process was convened to recommend terminology unified across lower anogenital sites. The goal was to create a histopathologic nomenclature system that reflects current knowledge of HPV biology, optimally uses available biomarkers, and facilitates clear communication across different medical specialties. The Lower Anogenital Squamous Terminology (LAST) Project was cosponsored by the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology and included 5 working groups; 3 work groups performed comprehensive literature reviews and developed draft recommendations. Another work group provided the historical background and the fifth will continue to foster implementation of the LAST recommendations. After an open comment period, the draft recommendations were presented at a consensus conference attended by LAST work group members, advisors, and representatives from 35 stakeholder organizations including professional societies and government agencies. Recommendations were finalized and voted on at the consensus meeting. The final, approved recommendations standardize biologically relevant histopathologic terminology for HPV-associated squamous intraepithelial lesions and superficially invasive squamous carcinomas across all lower anogenital tract sites and detail the appropriate use of specific biomarkers to clarify histologic interpretations and enhance diagnostic accuracy. A plan for disseminating and monitoring recommendation implementation in the practicing community was also developed. The implemented recommendations will facilitate communication between pathologists and their clinical colleagues and improve accuracy of histologic diagnosis with the ultimate goal of providing optimal patient care. C1 [Darragh, Teresa M.] Univ Calif San Francisco, Mt Zion Med Ctr, Dept Pathol & Obstet, San Francisco, CA 94115 USA. [Colgan, Terence J.] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Cox, J. Thomas; Heller, Debra S.] UMDNJ New Jersey Med Sch, Newark, NJ USA. [Henry, Michael R.] Mayo Clin, Rochester, MN USA. [Luff, Ronald D.] Quest Diagnost, Teterboro, NJ USA. [Luff, Ronald D.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Nayar, Ritu] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Stoler, Mark H.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Wilkinson, Edward J.] Univ Florida, Coll Med, Gainesville, FL USA. [Zaino, Richard J.] Penn State Univ, Milton S Hershey Med Ctr, Hershey, PA 17033 USA. [Wilbur, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Cox, J. Thomas] Univ Calif Santa Barbara, Santa Barbara Student Hlth Serv, Santa Barbara, CA 93106 USA. RP Darragh, TM (reprint author), Univ Calif San Francisco, Mt Zion Med Ctr, Dept Pathol & Obstet, 1600 Divisadero St,Room B618, San Francisco, CA 94115 USA. EM teresa.darragh@ucsf.edu FU American Society for Colposcopy and Cervical Pathology (ASCCP); College of American Pathologists (CAP); National Institutes of Health (NIH)/National Cancer Institute (NCI); NIH/National Institute of Allergy and infectious Disease; American College of Obstetricians and Gynecologists (ACOG); Society of Gynecologic Oncologists (SGO); Planned Parenthood, and the American Society for Clinical Pathology (ASCP); GlaxoSmithKline; BD TriPath; Pennsylvania State University; University of Washington; Oregon Dermatological Society; CAP; Cornell University; University of Iowa; Elsevier; US State Department and the US Agency for International Development; Lippincott; Williams; Wilkins; MTM Laboratories; BD Diagnostics; Veregen; OncoHealth; Indian Health Service; ASCCP; Gynecologic Oncology Group; ACOG; Michigan Hematology Oncology Association; NIH/NCI; ACOG District IV; Minority Health Research Committee; Toledo Hospital; Society of Obstetricians; Society of Obstetricians and Gynecologists of Canada (SOGC); Florida OBGYN Society; Kentucky ACOG Section; Indiana ACOG Section; ACOG District V; Miami Grand Rounds; Missouri OBGYN Associates; Ohio Dermatologic Association; Flint Hospital; University of Wisconsin; University of Connecticut; Turkish Society; NIH; Washington University in St Louis; Meridian Conferences; SOGC; Merck Frosst; Merck and Co.; Gilead Biosciences; American Social Health Association; University of Ottawa; Thai Red Cross; University of Minnesota; University of Illinois; University of British Columbia; Louisiana State University; American Association for Cancer Research; Gynecologic Oncology Society of Canada; University of Alberta; European Society for Sexual Medicine; Aura Biosciences; Australian Society for Colposcopy and Cervical Pathology; Merck Research Laboratories; Springer Verlag; Meriter Foundation; University of Chicago; Chicago Dermatology Society; Harvard Medical School; Oakstone Medical Publishing; National Library of Medicine; New Mexico Department of Health/ Center for Health Training, Center for Health Training (Austin, TX); SouthEast Alaska Regional Health Corporation; Arctic Slope Native Association; Yukon Kuskokwim Health Corporation; Breast Cancer Detection of Alaska; Sutter Medical Center of Santa Rosa Medical; AIDS Healthcare Foundation of Los Angeles; American Society of Colon and Rectal Surgeons; Merck and Company; NIH/AMC Working Group; Canadian Institute of Health Research; Institute of Science & Technology Partnerships, Canada; Canadian Health Research Institute; ASCP; ASC; Hartford Hospital; PA Association of Pathologists; Scientific Symposium International; Medical University of South Carolina; Burrough's Wellcome Fund; NIH/National Institute of General Medical Sciences; Hologic for the PALS Trial; Indiana University; McGill University; United States & Canadian Academy of Pathology; Cambridge Publishers; Wolters Kluwer; American Registry of Pathology; University of New Mexico School of Medicine; BD; Merck, Inc; Roche; Gen-Probe; Agency for Healthcare Research and Quality (AHRQ) FX The American Society for Colposcopy and Cervical Pathology (ASCCP) and College of American Pathologists (CAP) provided the funding for this project; no industry funds were used in the development of the consensus statements and recommendations.; Steering Committee: Dr Darragh serves on the advisory boards of OncoHealth and Arbor Vita Corporation; she owns stock in OncoHealth and receives grants from the National Institutes of Health (NIH)/National Cancer Institute (NCI) and NIH/National Institute of Allergy and infectious Disease. In addition, she receives fees for lecturing for the American College of Obstetricians and Gynecologists (ACOG), the American Society for Colposcopy and Cervical Pathology (ASCCP), Society of Gynecologic Oncologists (SGO), Planned Parenthood, and the American Society for Clinical Pathology (ASCP). Dr Henry receives royalties from the College of American Pathologists (CAP). Dr Luff is an employee of Quest Diagnostics and holds stock ownership in the corporation. Quest Diagnostics receives grants from GlaxoSmithKline, BD TriPath, and Hologic to support clinical trials. Dr Luff received coverage for his travel to an Endo Pharmaceuticals investigators' meeting. He serves on the Foundation Board of the American Society of Cytopathology (ASC). Dr McCalmont receives lecture fees from the Pennsylvania State University, University of Washington, and the Oregon Dermatological Society. He serves as an expert witness for Filice, Brown and receives consultancy fees from various law firms. Dr Wilbur serves as an expert witness for MCIC Vermont, Ohio State University, Promutual, Memorial Sloan-Kettering Cancer Center, CMIC, Lavin, O'Neill, CRICO, Claims Management, and the Mayo Clinic. He serves as a consultant for Becker Consulting. He receives lecture fees from CAP, Cornell University, and the University of Iowa and receives royalties from both CAP and Elsevier. He serves on an advisory board for Corista LLC and VisionGate. He receives grants from the US State Department and the US Agency for International Development. Dr Wilkinson serves as a consultant for Hologic and Guided Therapeutics and serves on the advisory boards of Merck, Inc, and the ASCCP. He receives royalties from Lippincott, Williams, and Wilkins and grants from MTM Laboratories. Dr Wilkinson owns stock in Johnson & Johnson and Procter & Gamble.; Work Group 1: Dr Cox serves on the advisory boards for Gen-Probe, Graceway, and Roche; he also serves on the Merck HPV Vaccine Data and Safety Monitoring Board. Dr Cox receives lecture fees from BD Diagnostics, Veregen, GlaxoSmithKline, and OncoHealth. Dennis O'Connor serves as a consultant to the National Children's Tissue Bank. He receives lecture fees from the Indian Health Service and the ASCCP and grants from the Gynecologic Oncology Group. R. Kevin Reynolds receives lecture fees from ACOG, ASCCP, and the Michigan Hematology Oncology Association. James Scurry (advisor) owns stocks in Sonic Health Care, Impedimed, Nib Holdings Limited, and Biota Holdings. M. Angelica Selim received a grant from NIH/NCI. For Dr Wilkinson, see Steering Committee listing.; Work Group 2: David Chelmow serves on the eMedicine Editorial Board and Medscape Reference Editorial Board. He has served as an expert witness for various obstetrical cases. He receives lecture fees from ACOG District IV. Leona Council is a part-time employee of LabCorp and receives grants from the Minority Health Research Committee. Hope Haefner has received lecture fees from ACOG, ASCCP, Toledo Hospital, Society of Obstetricians and Gynecologists of Canada (SOGC), Florida OBGYN Society, Kentucky ACOG Section, Indiana ACOG Section, ACOG District V, Miami Grand Rounds, Missouri OBGYN Associates, Ohio Dermatologic Association, Flint Hospital, University of Wisconsin, University of Connecticut, and the Turkish Society. She serves as an expert witness for Kitch Attorneys & Counselors. For Dr Henry, see Steering Committee listing. Lydia Howell serves on an advisory board for the American Council on Education and as an expert witness for Ubaldi and McPherson, LLC. She has received grants from NIH and lecture fees from Washington University in St Louis. Kieron Leslie serves both as a consultant and as an advisory board member for Novartis. Dr Leslie receives lecture fees from Meridian Conferences. Alice Lytwyn provides expert review and consulting for the Program for Appropriate Technology in Health. She receives lecture fees from the SOGC and Merck Frosst. Dr Lytwyn also receives grants from Merck Frosst. For Dr McCalmont, see Steering Committee listing. Joel Palefsky serves on the advisory boards of Merck and Co, Pharmajet, Inc, Aura Biosciences, Inc, and the Arbor Vita Corporation. He serves as a consultant and receives grants and travel expenses from Merck and Co. Dr Palefsky receives lecture fees from the Gilead Biosciences, American Social Health Association, University of Ottawa, Thai Red Cross, University of Minnesota, University of Illinois, University of British Columbia, Louisiana State University, American Association for Cancer Research, ASCCP, Gynecologic Oncology Society of Canada, University of Alberta, and the European Society for Sexual Medicine. He serves as an expert witness for the Schoenberg Law Firm. He receives grants from Aura Biosciences and NIH for research and royalties from UpToDate. Jennifer Roberts (advisor) receives lecture fees from the Australian Society for Colposcopy and Cervical Pathology. Brigitte Ronnett receives grants from NIH/NCI and Merck Research Laboratories. She serves as a consultant to Merck Research Laboratories and receives lecture fees from MTM Laboratories. She also receives royalties from Springer Verlag. Christopher Shea serves on the Editorial Board of the Journal of American Academy of Dermatology. He receives lecture fees from Meriter Foundation. Dr Shea serves as an expert witness for Healthcare Litigation Support, LLC, Wicker, Smith, O'Hara, McCoy & Ford, PA, Gary Osborne & Associates, Eichorn and Eichorn, and Benito H. Diaz, Esq. He receives grants from the University of Chicago, Chicago Dermatology Society, and NIH. Paul Staats receives lecture fees from Harvard Medical School. Alan Waxman serves on advisory boards for ACOG, ASCCP, the American Cancer Society Cervical Cancer Screening Work Group.; He receives a partial salary grant from NIH and lecture fees from ACOG, ASCCP, Oakstone Medical Publishing, the National Library of Medicine, the New Mexico Department of Health/ Center for Health Training, Center for Health Training (Austin, TX), SouthEast Alaska Regional Health Corporation, Arctic Slope Native Association, Yukon Kuskokwim Health Corporation, and Breast Cancer Detection of Alaska. Dr Waxman also receives a retirement pension from the United States Public Health Service.; Work Group 3: J. Michael Berry receives lecture fees from Sutter Medical Center of Santa Rosa Medical, AIDS Healthcare Foundation of Los Angeles, American Society of Colon and Rectal Surgeons, and ASCCP. He serves as a consultant for the Cancer Research Center of Hawaii. Dr Berry is employed by the University of California - San Francisco, which holds contracts and receives grants for the performance of research from Merck and Company and the NIH/AMC Working Group. He serves on an advisory board for Arbor Vita Corporation. Terence Colgan is a consultant for LifeLabs and Ontario Medical Associates. He receives lecture fees from the ASCCP and grants from the Canadian Institute of Health Research, Institute of Science & Technology Partnerships, Canada, and the Canadian Health Research Institute. He has patents pending or received relative to protein markers of endometrial cancer and endometrial biomarkers. He receives honoraria for serving as the Associate Editor of Cancer Cytopathology. For Dr Darragh, see Steering Committee listing. Levi Downs receives grants from GlaxoSmithKline. Olga Ioffe receives lecture fees from the ASCP. Nancy Joste serves on the Board of Directors for both Grounds for Health (NGO) and Planned Parenthood of New Mexico. She receives grants from the NIH/NCI. Oscar Lin receives grants from NIH and lecture fees from the ASC. Richard Zaino holds a consultancy with the United States Food & Drug Administration and serves as the co-chair of the NCI Uterine Task Force. He receives lecture fees from Hartford Hospital, PA Association of Pathologists, Gynecologic Oncology Group, CAP, Scientific Symposium International (travel reimbursement included), ASCP, and the Medical University of South Carolina.; Work Group 4: Christina Kong serves as an expert witness for PG&E, Rissman, Barrett, Hurt, Donahue, & McLain, PA, Garrett Hemann Robertson, PC, Martin & Jones, LLC, Cabaniss, Johnston, Gardner, Dumas, and O'Neal, LLP, and Andrada & Associates. She receives lecture fees from the California Society of Pathologists and grants from Burrough's Wellcome Fund and NIH. She received travel reimbursement from the Philippine Society of Pathologists. Bradley Quade serves as an expert witness for William E. Artz, PC, Bonezzi, Switzer, Murphy, Polito & Hupp, Co, LPA, Risk Management Foundation, Margolis Edelstein, Professional Casualty Association, Mary Hitchcock Memorial Hospital, University Hospitals Health System, Kline & Specter, Berman and Simmons, Martin, Magnuson, McCarthy & Kenney, Trobh, Heisler & Piampiano, and Foster & Eldridge. He serves on an advisory board for the Columbia Hospital Research Foundation and he receives a grant from NIH/National Institute of General Medical Sciences. Mark Stoler serves as a consultant to Merck Research Labs, Roche, Gen-Probe, Qiagen, BD, Ventana Medical Systems, MTM Laboratories, and Abraxis. For Dr Wilbur, see Steering Committee listing.; Work Group 5: Alicia Carter (advisor) is employed by Laboratory Corporation of America Holdings. Philip E. Castle serves as a consultant for Merck, Inc, and Roche. Maire Duggan receives grants (materials only, no funding) from Hologic for the PALS Trial. Francisco Garcia is employed by the University of Arizona, which holds contracts for the performance of research with Roche, Innovio, Photocure, Hologic, and BDD. Marc Goodman (advisor) is a consultant for Vanderbilt University, University of Iowa, the North American Association of Central Cancer Registries, and Moffitt Cancer Center. He serves on the Board of Scientific Counselors of NCI and receives grants from NIH for SEER, ovarian, and HPV research. For Dr Luff, see Steering Committee listing. Ann Moriarty is employed by AmeriPath and serves on the Cancer Support Community Physicians Advisory Board. She receives lecture fees from the ASC and serves as an expert witness for Eichorn and Eichorn, LLP. Ritu Nayar serves on the Cytopathology Test Development Committee for the American Board of Pathology and as an Associate Editor for Cancer (Cytopathology). She receives lecture fees from Indiana University, McGill University, and the United States & Canadian Academy of Pathology and receives grants from MTM Laboratories. Margaret Neal (advisor) serves on an advisory board for PathPAC. George Niedt serves as a consultant to Bronx Lebanon Hospital and Jacobi Hospital. Vijaya Reddy (advisor) receives royalties from both Cambridge Publishers and Elsevier. Mona Saraiya (advisor) serves on the American Cancer Society Steering Committee for Gynecologic Cancer. Susan Spires (advisor) receives lecture fees from CAP and ASC. Steve Silverberg (advisor) receives royalties from Elsevier, Wolters Kluwer, and the American Registry of Pathology. He receives lecture fees from the ASCP. Herschel Lawson (conference moderator) receives lecture fees from the University of New Mexico School of Medicine and the ASCCP. Thomas Wright (technical reviewer) serves as a consultant for GlaxoSmithKline, Roche Molecular Diagnostics, Merck, Inc, i3 Innovus, MTM Laboratories, Gen-Probe, and BD. He also serves on advisory boards for BD, Merck, Inc, and Roche. He receives lecture fees from BD, Merck, Inc, and Roche. Evan Myers (LAST methodologist) serves as a consultant for Gen-Probe, Merck, Inc, and GlaxoSmithKline. He serves on an advisory board for Merck, Inc and receives fees for lecturing for Gen-Probe. Dr Myers receives grants from Gen-Probe, GlaxoSmithKline, and the Agency for Healthcare Research and Quality (AHRQ). NR 181 TC 90 Z9 95 U1 0 U2 3 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD OCT PY 2012 VL 136 IS 10 BP 1266 EP 1297 PG 32 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 020PH UT WOS:000309824900019 PM 22742517 ER PT J AU Velmahos, GC AF Velmahos, George C. TI Posttraumatic Venous Thromboembolism as a "Never Event" Will Computers Help? INVITED CRITIQUE SO ARCHIVES OF SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Velmahos, GC (reprint author), Massachusetts Gen Hosp, Dept Surg, 165 Cambridge St,Ste 810, Boston, MA 02114 USA. EM gvelmahos@partners.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD OCT PY 2012 VL 147 IS 10 BP 908 EP 908 PG 1 WC Surgery SC Surgery GA 021WV UT WOS:000309917000003 PM 23070408 ER PT J AU Ohsumi, TK Borowsky, ML AF Ohsumi, Toshiro K. Borowsky, Mark L. TI MolBioLib: a C++11 framework for rapid development and deployment of bioinformatics tasks SO BIOINFORMATICS LA English DT Article ID SEQ; TOOLKIT; ARACHNE; MODEL; RNAS AB We developed MolBioLib to address the need for adaptable next-generation sequencing analysis tools. The result is a compact, portable and extensively tested C++11 software framework and set of applications tailored to the demands of next-generation sequencing data and applicable to many other applications. MolBioLib is designed to work with common file formats and data types used both in genomic analysis and general data analysis. A central relational-database-like Table class is a flexible and powerful object to intuitively represent and work with a wide variety of tabular datasets, ranging from alignment data to annotations. MolBioLib has been used to identify causative single-nucleotide polymorphisms in whole genome sequencing, detect balanced chromosomal rearrangements and compute enrichment of messenger RNAs (mRNAs) on microtubules, typically requiring applications of under 200 lines of code. MolBioLib includes programs to perform a wide variety of analysis tasks, such as computing read coverage, annotating genomic intervals and novel peak calling with a wavelet algorithm. Although MolBioLib was designed primarily for bioinformatics purposes, much of its functionality is applicable to a wide range of problems. Complete documentation and an extensive automated test suite are provided. C1 [Ohsumi, Toshiro K.; Borowsky, Mark L.] Massachusetts Gen Hosp, Dept Mol Biol, Richard B Simches Res Ctr, Boston, MA 02114 USA. [Ohsumi, Toshiro K.; Borowsky, Mark L.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Ohsumi, TK (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Richard B Simches Res Ctr, 185 Cambridge St,CPZN 7250, Boston, MA 02114 USA. EM ohsumit@molbio.mgh.harvard.edu NR 40 TC 7 Z9 7 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD OCT 1 PY 2012 VL 28 IS 19 BP 2412 EP 2416 DI 10.1093/bioinformatics/bts458 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 018UA UT WOS:000309687500002 PM 22815363 ER PT J AU Gusenleitner, D Howe, EA Bentink, S Quackenbush, J Culhane, AC AF Gusenleitner, Daniel Howe, Eleanor A. Bentink, Stefan Quackenbush, John Culhane, Aedin C. TI iBBiG: iterative binary bi-clustering of gene sets SO BIOINFORMATICS LA English DT Article ID BREAST-CANCER PROGRESSION; ENRICHMENT ANALYSIS; EXPRESSION DATA; BIOLOGICAL PROCESSES; MICROARRAY DATA; DISEASES; DATABASE; CCL5 AB Motivation: Meta-analysis of genomics data seeks to identify genes associated with a biological phenotype across multiple datasets; however, merging data from different platforms by their features (genes) is challenging. Meta-analysis using functionally or biologically characterized gene sets simplifies data integration is biologically intuitive and is seen as having great potential, but is an emerging field with few established statistical methods. Results: We transform gene expression profiles into binary gene set profiles by discretizing results of gene set enrichment analyses and apply a new iterative bi-clustering algorithm (iBBiG) to identify groups of gene sets that are coordinately associated with groups of phenotypes across multiple studies. iBBiG is optimized for meta-analysis of large numbers of diverse genomics data that may have unmatched samples. It does not require prior knowledge of the number or size of clusters. When applied to simulated data, it outperforms commonly used clustering methods, discovers overlapping clusters of diverse sizes and is robust in the presence of noise. We apply it to meta-analysis of breast cancer studies, where iBBiG extracted novel gene set-phenotype association that predicted tumor metastases within tumor subtypes. C1 [Gusenleitner, Daniel; Howe, Eleanor A.; Bentink, Stefan; Quackenbush, John; Culhane, Aedin C.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Howe, Eleanor A.] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [Bentink, Stefan; Quackenbush, John; Culhane, Aedin C.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Quackenbush, John] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Culhane, AC (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. EM aedin@jimmy.harvard.edu FU Claudia Adams Barr foundation; National Cancer Institute of the US National Institutes of Health [1U19CA148065] FX This work was supported the Claudia Adams Barr foundation and grant 1U19CA148065 from the National Cancer Institute of the US National Institutes of Health. We are grateful to Prof. Curtis Huttenhower for his invaluable expertise and generous help in running COALESCE. We thank Benjamin Haibe-Kains and Stephan Winkler for valuable comments during the development of the algorithm, Markus Schroder for offering his expertise on implementing the R functions as C libraries and Prof. Daniel Silver for assistance in biological interpretation of results of the analyses. NR 41 TC 8 Z9 8 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 EI 1460-2059 J9 BIOINFORMATICS JI Bioinformatics PD OCT 1 PY 2012 VL 28 IS 19 BP 2484 EP 2492 DI 10.1093/bioinformatics/bts438 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 018UA UT WOS:000309687500011 PM 22789589 ER PT J AU Goldstein, JI Crenshaw, A Carey, J Grant, GB Maguire, J Fromer, M O'Dushlaine, C Moran, JL Chambert, K Stevens, C Sklar, P Hultman, CM Purcell, S McCarroll, SA Sullivan, PF Daly, MJ Neale, BM AF Goldstein, Jacqueline I. Crenshaw, Andrew Carey, Jason Grant, George B. Maguire, Jared Fromer, Menachem O'Dushlaine, Colm Moran, Jennifer L. Chambert, Kimberly Stevens, Christine Sklar, Pamela Hultman, Christina M. Purcell, Shaun McCarroll, Steven A. Sullivan, Patrick F. Daly, Mark J. Neale, Benjamin M. CA Swedish Schizophrenia Consortium ARRA Autism Sequencing Consortium TI zCall: a rare variant caller for array-based genotyping SO BIOINFORMATICS LA English DT Article AB zCall is a variant caller specifically designed for calling rare single-nucleotide polymorphisms from array-based technology. This caller is implemented as a post-processing step after a default calling algorithm has been applied. The algorithm uses the intensity profile of the common allele homozygote cluster to define the location of the other two genotype clusters. We demonstrate improved detection of rare alleles when applying zCall to samples that have both Illumina Infinium HumanExome BeadChip and exome sequencing data available. C1 [Goldstein, Jacqueline I.; Fromer, Menachem; Purcell, Shaun; Daly, Mark J.; Neale, Benjamin M.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Goldstein, Jacqueline I.; Fromer, Menachem; Purcell, Shaun; Daly, Mark J.; Neale, Benjamin M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Goldstein, Jacqueline I.; Maguire, Jared; Fromer, Menachem; Stevens, Christine; McCarroll, Steven A.; Daly, Mark J.; Neale, Benjamin M.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Fromer, Menachem; Sklar, Pamela; Purcell, Shaun] Mt Sinai Sch Med, Dept Psychiat, Div Psychiat Genom, New York, NY 10029 USA. [O'Dushlaine, Colm; Moran, Jennifer L.; Chambert, Kimberly; Purcell, Shaun; McCarroll, Steven A.; Neale, Benjamin M.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Hultman, Christina M.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [McCarroll, Steven A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Sullivan, Patrick F.] Univ N Carolina, Chapel Hill Sch Med, Dept Genet, Chapel Hill, NC 27514 USA. RP Neale, BM (reprint author), Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. EM bneale@broadinstitute.org OI Goldstein, Jacqueline/0000-0003-1902-6916; Moran, Jennifer/0000-0002-5664-4716 FU Swedish Council for Working Life and Social Research [FO 184/2000, 2001-2368]; National Institutes of Health [MH079126, MH089208, MH089025, MH089004, MH089175, MH089482]; Gerstner Family Foundation; Stanley Medical Research Institute FX The Swedish Council for Working Life and Social Research (FO 184/2000; 2001-2368); the National Institutes of Health (MH079126, MH089208, MH089025, MH089004, MH089175, MH089482); the Gerstner Family Foundation and the Stanley Medical Research Institute. NR 8 TC 55 Z9 55 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD OCT 1 PY 2012 VL 28 IS 19 BP 2543 EP 2545 DI 10.1093/bioinformatics/bts479 PG 3 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 018UA UT WOS:000309687500026 PM 22843986 ER PT J AU Westover, K Chen, MH Moul, J Robertson, C Polascik, T Dosoretz, D Katin, M Salenius, S D'Amico, AV AF Westover, Kenneth Chen, Ming-Hui Moul, Judd Robertson, Cary Polascik, Thomas Dosoretz, Daniel Katin, Michael Salenius, Sharon D'Amico, Anthony V. TI Radical prostatectomy vs radiation therapy and androgen-suppression therapy in high-risk prostate cancer SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; hormonal therapy; radical prostatectomy ID EXTERNAL-BEAM RADIATION; PERINEURAL INVASION; BIOCHEMICAL OUTCOMES; COMPETING RISK; PSA VELOCITY; FOLLOW-UP; RADIOTHERAPY; SURVIVAL; MEN; DEATH AB OBJECTIVE To assess the risk of prostate cancer-specific mortality after therapy with radical prostatectomy (RP) or combined-modality therapy (CMT) with brachytherapy, external beam radiation therapy (EBRT) and androgen-suppression therapy (AST) in men with Gleason score 8-10 prostate cancer. PATIENTS AND METHODS Men with localised high-risk prostate cancer based on a Gleason score of 8-10 were selected for study from Duke University (285 men), treated between January 1988 and October 2008 with RP or from the Chicago Prostate Cancer Center or within the 21st Century Oncology establishment (372) treated between August 1991 and November 2005 with CMT. Fine and Gray multivariable regression was used to assess whether the risk of prostate cancer-specific mortality differed after RP as compared with CMT adjusting for age, cardiac comorbidity and year of treatment, and known prostate cancer prognostic factors. RESULTS As of January 2009, with a median (interquartile range) follow-up of 4.62 (2.4-8.2) years, there were 21 prostate cancerspecific deaths. Treatment with RP was not associated with an increased risk of prostate cancer-specific mortality compared with CMT (adjusted hazard ratio [HR] 1.8, 95% confidence interval [CI] 0.6-5.6, P = 0.3). Factors associated with an increased risk of prostate cancer-specific mortality were a PSA concentration of <4 ng/mL (adjusted HR 6.1, 95% CI 2.3-16, P < 0.001) as compared with >= 4 ng/mL, and clinical category T2b, c (adjusted HR 2.9; 95% CI 1.1-7.2; P = 0.03) as compared with T1c, 2a. CONCLUSION Initial treatment with RP as compared with CMT was not associated with an increased risk of prostate cancer-specific mortality in men with Gleason score 8-10 prostate cancer. C1 [Westover, Kenneth; D'Amico, Anthony V.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Westover, Kenneth; D'Amico, Anthony V.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Moul, Judd; Robertson, Cary; Polascik, Thomas] Duke Univ, Med Ctr, Div Urol Surg, Durham, NC USA. [Moul, Judd; Robertson, Cary; Polascik, Thomas] Duke Univ, Med Ctr, Dept Surg, Duke Prostate Ctr, Durham, NC 27710 USA. [Dosoretz, Daniel; Katin, Michael; Salenius, Sharon] 21st Century Oncol, Ft Myers, FL USA. RP Westover, K (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St,L-2 Level, Boston, MA 02115 USA. EM kwestover@partners.org NR 24 TC 18 Z9 19 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 J9 BJU INT JI BJU Int. PD OCT PY 2012 VL 110 IS 8 BP 1116 EP 1121 DI 10.1111/j.1464-410X.2012.11012.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 014RQ UT WOS:000309393800009 PM 22540922 ER PT J AU Dellapasqua, S Bagnardi, V Regan, MM Rotmensz, N Mastropasqua, MG Viale, G Maiorano, E Price, KN Gelber, RD Castiglione-Gertsch, M Goldhirsch, A Colleoni, M AF Dellapasqua, Silvia Bagnardi, Vincenzo Regan, Meredith M. Rotmensz, Nicole Mastropasqua, Mauro G. Viale, Giuseppe Maiorano, Eugenio Price, Karen N. Gelber, Richard D. Castiglione-Gertsch, Monica Goldhirsch, Aron Colleoni, Marco TI A risk score based on histopathological features predicts higher risk of distant recurrence in premenopausal patients with lymph node-negative endocrine-responsive breast cancer SO BREAST LA English DT Article DE Breast cancer; Histopathological features; Risk score; Endocrine therapy; Chemotherapy ID TREATMENT-COVARIATE INTERACTIONS; RANDOMIZED-TRIALS; PREOPERATIVE CHEMOTHERAPY; SURVIVAL ANALYSIS; GENE-EXPRESSION; ADJUVANT; THERAPY; SYSTEM; SAMPLE; MODEL AB Purpose: To develop a Risk Score (RS) to predict distant recurrence among premenopausal women with node-negative endocrine-responsive early breast cancer. Methods: The Cox model was used to develop the RS using clinical and histopathological features from 378 women participating in the IBCSG Trial VIII who received endocrine therapy alone or following chemotherapy. The performance of the resulting model was validated on a cohort of 1005 patients from a single institution who received endocrine therapy alone. Results: In a multivariable analysis, the risk of distant recurrence was associated with tumor size, ER, Ki-67 and peritumoral vascular invasion. In the validation cohort, patients with high RS were at greater risk of distant recurrence compared to patients with low RS (HR, 17.41; 95% CI, 5.72-52.95). Conclusion: In premenopausal women with node-negative endocrine-responsive early breast cancer, the RS identifies patients at higher risk of distant recurrence. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Dellapasqua, Silvia; Colleoni, Marco] European Inst Oncol, Med Senol Res Unit, I-20141 Milan, Italy. [Dellapasqua, Silvia; Colleoni, Marco] European Inst Oncol, Div Med Oncol, Dept Med, I-20141 Milan, Italy. [Bagnardi, Vincenzo] Univ Milano Bicocca, Dept Stat, European Inst Oncol, Div Epidemiol & Biostat, Milan, Italy. [Bagnardi, Vincenzo] Frontier Sci & Technol Res Fdn So Europe, Chiasso, Switzerland. [Regan, Meredith M.] Harvard Univ, Sch Med, Dana Farber Canc Inst,Stat Ctr, Int Breast Canc Study Grp,Dept Biostat & Comp Bio, Boston, MA 02115 USA. [Mastropasqua, Mauro G.; Viale, Giuseppe] Univ Milan, European Inst Oncol, Div Pathol & Lab Med, Milan, Italy. [Mastropasqua, Mauro G.; Viale, Giuseppe] Univ Milan, Int Breast Canc Study Grp, Cent Pathol Off, Milan, Italy. [Maiorano, Eugenio] Univ Bari Aldo Moro, Dept Pathol Anat, Bari, Italy. [Price, Karen N.; Gelber, Richard D.] Frontier Sci & Technol Res Fdn Inc, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Int Breast Canc Study Grp,Stat Ctr, Boston, MA USA. [Castiglione-Gertsch, Monica] Univ Geneva, Dept Med Hop, Unite Oncogynecol Med, CH-0223824 Geneva, Switzerland. [Goldhirsch, Aron] Swiss Ctr Breast Hlth, St Anna Clin, Lugano, Switzerland. RP Dellapasqua, S (reprint author), European Inst Oncol, Med Senol Res Unit, Via Ripamonti 435, I-20141 Milan, Italy. EM silvia.dellapasqua@ieo.it; vincenzo.bagnardi@ieo.it; mregan@jimmy.harvard.edu; nicole.rotmensz@ieo.it; Mauro.Mastropasqua@ieo.it; giuseppe.viale@ieo.it; emaiorano@anatopat.uniba.it; price@jimmy.harvard.edu; gelber@jimmy.harvard.edu; monica.castiglione@bluewin.ch; aron.goldhirsch@ibcsg.org; marco.colleoni@ieo.it RI Maiorano, Eugenio/F-1382-2015; OI Maiorano, Eugenio/0000-0002-0472-5338 FU Cancer Council Australia, Australian New Zealand Breast Cancer Trials Group (NHMRC) [890027, 920875, 950327, 980378, 141710]; Cancer Association of South Africa; Foundation for Clinical Research of Eastern Switzerland (OSKK); Swedish Society for Cancer Research (Cancerfonden); International Breast Cancer Study Group FX We thank the patients, investigators, and researchers involved in the long-term follow-up of this IBCSG trial. We thank the following groups for continuing support for the International Breast Cancer Study Group: The Cancer Council Australia, Australian New Zealand Breast Cancer Trials Group (NHMRC grant numbers 890027, 920875, 950327, 980378, 141710), the Frontier Science and Technology Research Foundation, the Swiss Group for Clinical Cancer Research (SAKK), the Swiss Cancer League, and the United States National Cancer Institute (CA-75362). We also acknowledge support for the Cape Town participants from the Cancer Association of South Africa, for the St. Gallen participants from the Foundation for Clinical Research of Eastern Switzerland (OSKK), and for the Gothenburg participants from the Swedish Society for Cancer Research (Cancerfonden). The study was sponsored by the International Breast Cancer Study Group, and no external organizations were involved in the writing of this paper. NR 21 TC 0 Z9 0 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD OCT PY 2012 VL 21 IS 5 BP 621 EP 628 DI 10.1016/j.breast.2012.06.003 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 020HP UT WOS:000309799900002 PM 22749924 ER PT J AU Larsen, MS Bjerre, K Lykkesfeldt, AE Giobbie-Hurder, A Laenkholm, AV Henriksen, KL Ejlertsen, B Rasmussen, BB AF Larsen, Mathilde S. Bjerre, Karsten Lykkesfeldt, Anne E. Giobbie-Hurder, Anita Laenkholm, Anne-Vibeke Henriksen, Katrine L. Ejlertsen, Bent Rasmussen, Birgitte B. TI Activated HER-receptors in predicting outcome of ER-positive breast cancer patients treated with adjuvant endocrine therapy SO BREAST LA English DT Article DE Breast cancer; ER-positive; Endocrine resistance; HER-receptors; Phosphorylated HER ID GROWTH-FACTOR RECEPTOR; MESSENGER-RNA EXPRESSION; ESTROGEN-RECEPTOR; TAMOXIFEN RESISTANCE; PROGESTERONE-RECEPTOR; AROMATASE INHIBITORS; TISSUE MICROARRAYS; PROGNOSTIC VALUE; CARCINOMAS; FAMILY AB The four human epidermal growth factor receptors (HER1-4) are involved in growth stimulation and may play a role in endocrine resistance. The receptors form dimers, leading to activation by mutual phosphorylation. Our purpose was to explore the role of the activated receptors (pHER1, pHER2 pHER3) in endocrine treated breast cancer in terms of co-expression and association with disease-free survival (DFS) in 1062 patients with ER-positive tumors. Furthermore, HER2 amplification was evaluated. We found positive associations between the phosphorylated receptors. pHER1 and pHER3 were co-expressed with one or two of the other activated receptors in 85% and 89% of tumors, respectively, whereas pHER2 was co-expressed with the other activated receptors in 54% of tumors. Except for HER2, which was associated with poor prognosis, none of the remaining markers were associated with DFS. However, frequent co-expression indicates a role of the other HER-family members in activation of HER2. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Larsen, Mathilde S.; Rasmussen, Birgitte B.] Herlev Hosp, Dept Pathol, DK-2730 Herlev, Denmark. [Larsen, Mathilde S.; Lykkesfeldt, Anne E.; Henriksen, Katrine L.] Danish Canc Soc, Inst Canc Biol, Dept Breast Canc Res, DK-2100 Copenhagen O, Denmark. [Bjerre, Karsten; Ejlertsen, Bent] Rigshosp, Danish Breast Canc Cooperat Grp, DK-2100 Copenhagen O, Denmark. [Giobbie-Hurder, Anita] Dana Farber Canc Inst, IBCSG Stat Ctr, Boston, MA 02115 USA. [Laenkholm, Anne-Vibeke] Odense Univ Hosp, Dept Pathol, DK-5000 Odense C, Denmark. RP Larsen, MS (reprint author), Herlev Hosp, Dept Pathol, Herlev Ringvej 75, DK-2730 Herlev, Denmark. EM mathilde.skaarup.larsen@regionh.dk; kb@dbcg.dk; al@cancer.dk; agiohur@jimmy.harvard.edu; anlae@regionsjaelland.dk; k.weischenfeldt@gmail.com; be@dbcg.dk; birgitte.bruun.rasmussen@regionh.dk FU Breast Friends; Dansk Kraeftforsknings Fond; Danish Agency for Science Technology and Innovation [09-063068, 09-066017]; A Race Against Breast Cancer; US National Institutes of Health [CA-75362] FX We wish to thank "Breast Friends", "Dansk Kraeftforsknings Fond", "Danish Agency for Science Technology and Innovation" (grant nos 09-063068 and 09-066017) and "A Race Against Breast Cancer" for financial support. Partial funding was provided by the US National Institutes of Health (grant no CA-75362). NR 41 TC 3 Z9 3 U1 0 U2 5 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD OCT PY 2012 VL 21 IS 5 BP 662 EP 668 DI 10.1016/j.breast.2012.07.005 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 020HP UT WOS:000309799900009 PM 22854050 ER PT J AU Mandal, CC Ghosh-Choudhury, T Dey, N Choudhury, GG Ghosh-Choudhury, N AF Mandal, Chandi Charan Ghosh-Choudhury, Triparna Dey, Nirmalya Choudhury, Goutam Ghosh Ghosh-Choudhury, Nandini TI miR-21 is targeted by omega-3 polyunsaturated fatty acid to regulate breast tumor CSF-1 expression SO CARCINOGENESIS LA English DT Article ID COLONY-STIMULATING FACTOR; CANCER CELLS; FACTOR-I; GENE-EXPRESSION; GROWTH-FACTOR; PHOSPHATIDYLINOSITOL 3-KINASE; MAMMARY-GLAND; PTEN; MICRORNAS; RECEPTOR AB Increasing evidence shows the beneficial effects of fish oil on breast cancer growth and invasion in vitro and in animal models. Expression of CSF-1 (colony stimulating factor-1) by breast cancer cells acts as potent activator of malignancy and metastasis. In this report, we used two human breast cancer cell lines, MDA-MB-231 and MCF-7, to show that the bioactive fish oil component DHA (docosahexaenoic acid) inhibits expression of CSF-1 and its secretion from these cancer cells. We found that the tumor suppressor protein PTEN regulates CSF-1 expression through PI 3 kinase/Akt signaling via a transcriptional mechanism. The enhanced abundance of microRNA-21 (miR-21) in breast cancer cells contributes to the growth and metastasis. Interestingly, DHA significantly inhibited expression of miR-21. miR-21 Sponge, which derepresses the miR-21 targets, markedly decreased expression of CSF-1 and its secretion. Furthermore, miR-21-induced upregulation of CSF-1 mRNA and its transcription were prevented by expression of PTEN mRNA lacking 3-untranslated region (UTR) and miR-21 recognition sequence. Strikingly, miR-21 reversed DHA-forced reduction of CSF-1 expression and secretion. Finally, we found that expression of miR-21 as well as CSF-1 was significantly attenuated in breast tumors of mice receiving a diet supplemented with fish oil. Our results reveal a novel mechanism for the therapeutic function of fish oil diet that blocks miR-21, thereby increasing PTEN levels to prevent expression of CSF-1 in breast cancer. C1 [Mandal, Chandi Charan; Ghosh-Choudhury, Triparna; Ghosh-Choudhury, Nandini] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. [Choudhury, Goutam Ghosh; Ghosh-Choudhury, Nandini] S Texas Vet Hlth Care Syst, VA Res, San Antonio, TX USA. [Choudhury, Goutam Ghosh] S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. [Dey, Nirmalya; Choudhury, Goutam Ghosh] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. RP Ghosh-Choudhury, N (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. EM choudhuryg@uthscsa.edu; choudhury@uthscsa.edu FU National Institutes of Health [RO1 AR52425, RO1 DK50190]; Cancer Therapy and Research Center; VA Merit review grants; VA Senior Research Career Scientist Award; VA Research Service Merit Review grant; Juvenile Diabetes Research Foundation [1-2008-185]; Cancer Prevention Research Institute of Texas post-doctoral fellowship FX National Institutes of Health (RO1 AR52425), Ronald Williams Orthopedic Award from the Cancer Therapy and Research Center, and VA Merit review grants to N.G.C. supported this work. Part of the work was supported by National Institutes of Health (RO1 DK50190) grant (to G.G.C.).; We thank Dr Anthony Valente, Associate Professor, Department of Medicine, University of Texas Health Science Center, San Antonio, TX, USA, for critically reading the manuscript. G. G. C. is a recipient of VA Senior Research Career Scientist Award and is supported by VA Research Service Merit Review grant and Juvenile Diabetes Research Foundation 1-2008-185 grant. C. C. M. is a recipient of Cancer Prevention Research Institute of Texas post-doctoral fellowship. NR 57 TC 33 Z9 35 U1 1 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 2012 VL 33 IS 10 BP 1897 EP 1908 DI 10.1093/carcin/bgs198 PG 12 WC Oncology SC Oncology GA 018XJ UT WOS:000309700900009 PM 22678116 ER PT J AU Garshick, E Laden, F Hart, JE Davis, ME Eisen, EA Smith, TJ AF Garshick, Eric Laden, Francine Hart, Jaime E. Davis, Mary E. Eisen, Ellen A. Smith, Thomas J. TI Cox Model Setup: Garshick et al. Respond SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter C1 [Garshick, Eric] Harvard Univ, Sch Med, Pulm & Crit Care Med Sect, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Laden, Francine; Hart, Jaime E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med, Boston, MA 02115 USA. [Davis, Mary E.] Tufts Univ, Dept Urban & Environm Policy & Planning, Medford, MA 02155 USA. [Eisen, Ellen A.] Univ Calif Berkeley, Sch Publ Hlth, Environm Hlth Sci Div, Berkeley, CA 94720 USA. [Smith, Thomas J.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program, Boston, MA 02115 USA. RP Garshick, E (reprint author), Harvard Univ, Sch Med, Pulm & Crit Care Med Sect, VA Boston Healthcare Syst, Boston, MA 02115 USA. EM Eric.Garshick@va.gov NR 2 TC 0 Z9 0 U1 0 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 2012 VL 120 IS 10 BP A382 EP A383 DI 10.1289/ehp.1205573R PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 018US UT WOS:000309692600003 ER PT J AU Korvala, J Loija, M Makitie, O Sochett, E Juppner, H Schnabel, D Mora, S Cole, WG Ala-Kokko, L Mannikko, M AF Korvala, Johanna Loija, Marika Makitie, Outi Sochett, Etienne Juppner, Harald Schnabel, Dirk Mora, Stefano Cole, William G. Ala-Kokko, Leena Mannikko, Minna TI Rare variations in WNT3A and DKK1 may predispose carriers to primary osteoporosis SO EUROPEAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE Bone; Osteoporosis; Genetics; DKK1; WNT3A ID OSTEOBLAST DIFFERENTIATION; MULTIPLE-MYELOMA; BONE-DENSITY; MUTATIONS; GENES; INHIBITION; EXPRESSION; MECHANISM; CELLS; WOMEN AB Childhood-onset primary osteoporosis is manifested as reduced bone mineral density, peripheral fractures and/or vertebral compression fractures. Until now, only mutations in LRP5 have been shown to cause the disorder. Candidate gene analyses were performed on 15 patients with primary osteoporosis and 80 healthy controls using CSGE and sequencing. The genes studied included DKK1, DKK2, WNT3A, WNT10B, AXIN1, SOST, TPH1 and 5-HTR1B. Two rare variants in WNT3A (c.152A > G, p.K51R) and DKK1 (c.359G > T, p.R120L) were identified in two patients and their affected family members, but not in control subjects, suggesting a significance for the skeletal phenotype. The in vitro studies of variants showed reduced signaling activity in p. K51R-Wnt3a, while no differences were observed between the WT and variant forms of DKK1. This study addresses the role of other components of the canonical Wnt signaling pathway besides LRP5 in primary osteoporosis, and putatively associates WNT3A and DKK1 variants with the disorder. Future functional studies are needed to elucidate the functional effects of the variants. (C) 2012 Elsevier Masson SAS. All rights reserved. C1 [Korvala, Johanna; Loija, Marika; Ala-Kokko, Leena; Mannikko, Minna] Univ Oulu, Dept Med Biochem & Mol Biol, Inst Biomed, Oulu 90014, Finland. [Korvala, Johanna; Loija, Marika; Ala-Kokko, Leena; Mannikko, Minna] Univ Oulu, Oulu Ctr Cell Matrix Res, Bioctr, Oulu 90014, Finland. [Makitie, Outi] Univ Helsinki, Childrens Hosp, Cent Hosp, Helsinki, Finland. [Juppner, Harald] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Juppner, Harald] Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Schnabel, Dirk] Charite, Dept Pediat Endocrinol & Diabet, Otto Heubner Ctr Kinder & Jugendmed, D-13353 Berlin, Germany. [Mora, Stefano] Ist Sci San Raffaele, Lab Pediat Endocrinol, BoNetwork, Div Metab & Cardiovasc Sci, I-20132 Milan, Italy. [Cole, William G.] Univ Toronto, Hosp Sick Children, Div Orthopaed Surg, Toronto, ON M5G 1X8, Canada. [Ala-Kokko, Leena] Connect Tissue Gene Tests, Allentown, PA USA. RP Korvala, J (reprint author), Univ Oulu, Dept Med Biochem & Mol Biol, Inst Biomed, POB 5000, Oulu 90014, Finland. EM johanna.korvala@oulu.fi RI Mora, Sefano/B-2143-2013; OI Makitie, Outi/0000-0002-4547-001X FU Finnish Cultural Foundation; Academy of Finland; Alma and K.A. Snellman Foundation, Oulu, Finland; Olga and Vilho Linnamo Foundation; Emil Aaltonen Foundation; Orion-Farmos Research Foundation FX We thank all the patients and their family members for participating in this study. We are grateful to Prof. Warman for providing the WT-LRP5 and WT-DKK1 constructs and to Prof. Vainio for the STF and beta-Gal-CMV constructs. The laboratory technicians Aira Erkkila and Helena Satulehto are warmly thanked for their technical assistance. The study was supported by grants from the Finnish Cultural Foundation (to MM, LA-K and JK), the Academy of Finland (LA-K), the Alma and K.A. Snellman Foundation, Oulu, Finland (JK), the Olga and Vilho Linnamo Foundation (JK), the Emil Aaltonen Foundation (JK) and the Orion-Farmos Research Foundation (JK). NR 24 TC 11 Z9 13 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1769-7212 J9 EUR J MED GENET JI Eur. J. Med. Genet. PD OCT PY 2012 VL 55 IS 10 BP 515 EP 519 DI 10.1016/j.ejmg.2012.06.011 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 019MI UT WOS:000309743500003 PM 22789636 ER PT J AU Bumbacea, D Arend, SM Eyuboglu, F Fishman, JA Goletti, D Ison, MG Jones, CE Kampmann, B Kotton, CN Lange, C Ljungman, P Milburn, H Morris, MI Muller, E Munoz, P Nellore, A Rieder, HL Sester, U Theodoropoulos, N Wagner, D Sester, M AF Bumbacea, Dragos Arend, Sandra M. Eyuboglu, Fusun Fishman, Jay A. Goletti, Delia Ison, Michael G. Jones, Christine E. Kampmann, Beate Kotton, Camille N. Lange, Christoph Ljungman, Per Milburn, Heather Morris, Michele I. Muller, Elmi Munoz, Patricia Nellore, Anoma Rieder, Hans L. Sester, Urban Theodoropoulos, Nicole Wagner, Dirk Sester, Martina TI The risk of tuberculosis in transplant candidates and recipients: a TBNET consensus statement SO EUROPEAN RESPIRATORY JOURNAL LA English DT Review DE Guideline; management; Mycobacterium tuberculosis; transplantation; tuberculosis ID GAMMA-RELEASE ASSAYS; MULTIDRUG-RESISTANT TUBERCULOSIS; STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; QUANTIFERON-TB GOLD; OF-THE-LITERATURE; MYCOBACTERIUM-TUBERCULOSIS; LATENT TUBERCULOSIS; ACTIVE TUBERCULOSIS; PULMONARY TUBERCULOSIS AB Tuberculosis (TB) is a possible complication of solid organ and hematopoietic stem cell transplantation. The identification of candidates for preventive chemotherapy is an effective intervention to protect transplant recipients with latent infection with Mycobacterium tuberculosis from progressing to active disease. The best available proxy for diagnosing latent infection with M. tuberculosis is the identification of an adaptive immune response by the tuberculin skin test or an interferon-gamma based ex vivo assay. Risk assessment in transplant recipients for the development of TB depends on, among other factors, the locally expected underlying prevalence of infection with M. tuberculosis in the target population. In areas of high prevalence, preventive chemotherapy for all transplant recipients may be justified without immunodiagnostic testing while in areas of medium and low prevalence, preventive chemotherapy should only be offered to candidates with positive M. tuberculosis-specific immune responses. The diagnosis of TB in transplant recipients can be challenging. Treatment of TB is often difficult due to substantial interactions between anti-TB drugs and immunosuppressive medications. This management guideline summarises current knowledge on the prevention, diagnosis and treatment of TB related to solid organ and hematopoietic stem cell transplantation and provides an expert consensus on questions where scientific evidence is still lacking. C1 [Sester, Martina] Univ Saarland, Dept Transplant & Infect Immunol, D-66421 Homburg, Germany. [Wagner, Dirk] Univ Freiburg, Ctr Chron Immunodeficiency, D-79106 Freiburg, Germany. [Wagner, Dirk] Univ Freiburg, Dept Infect Dis, D-79106 Freiburg, Germany. [Theodoropoulos, Nicole] Northwestern Univ, Feinberg Sch Med, Div Organ Transplantat, Chicago, IL 60611 USA. [Sester, Urban] Univ Saarland, Dept Internal Med 4, D-66421 Homburg, Germany. [Rieder, Hans L.] Univ Zurich, Inst Social & Prevent Med, CH-8006 Zurich, Switzerland. [Rieder, Hans L.] Int Union TB & Lung Dis, Paris, France. [Fishman, Jay A.; Kotton, Camille N.; Nellore, Anoma] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Infect Dis & Compromised Host Progra, Boston, MA USA. [Munoz, Patricia] Univ Complutense Madrid, Dept Med, Hosp Gen Univ Gregorio Maranon, Madrid, Spain. [Muller, Elmi] Groote Schuur Hosp, ZA-7925 Cape Town, South Africa. [Morris, Michele I.] Univ Miami, Miller Sch Med, Div Infect Dis, Miami, FL 33136 USA. [Milburn, Heather] Guys & St Thomas Hosp, Dept Resp Med, London SE1 9RT, England. [Ljungman, Per] Karolinska Inst, Stockholm, Sweden. [Ljungman, Per] Karolinska Univ Hosp, Stockholm, Sweden. [Lange, Christoph] Res Ctr Borstel, Med Clin, Div Clin Infect Dis, Borstel, Germany. [Jones, Christine E.; Kampmann, Beate] Univ London Imperial Coll Sci Technol & Med, London, England. [Ison, Michael G.] Northwestern Univ, Feinberg Sch Med, Div Organ Transplantat, Chicago, IL 60611 USA. [Goletti, Delia] Natl Inst Infect Dis L Spallanzani, Rome, Italy. [Eyuboglu, Fusun] Baskent Univ, Dept Pulm Dis, Sch Med, TR-06490 Ankara, Turkey. [Arend, Sandra M.] Leiden Univ, Dept Infect Dis, Med Ctr, Leiden, Netherlands. [Bumbacea, Dragos] Elias Emergency Univ Hosp, Dept Pneumol, Bucharest, Romania. [Bumbacea, Dragos] Carol Davila Univ Med & Pharm, Bucharest, Romania. RP Sester, M (reprint author), Univ Saarland, Dept Transplant & Infect Immunol, Kirrberger Str, D-66421 Homburg, Germany. EM martina.sester@uks.eu RI Wagner, Dirk/G-4598-2013; Lange, Christoph/J-6289-2012; Muller, Elmi/I-3258-2014; Wagner, Dirk/D-9778-2016; OI Muller, Elmi/0000-0003-4891-5296; Wagner, Dirk/0000-0002-3271-5815; Munoz Garcia, Patricia Carmen/0000-0001-5706-5583; Kampmann, Beate/0000-0002-6546-4709; Goletti, Delia/0000-0001-8360-4376; Sester, Martina/0000-0001-5482-0002 FU CNCSIS- UEFISCSU [PNII-IDEI 1447/2008] FX D. Bumbacea was supported by a grant from CNCSIS- UEFISCSU (grant PNII-IDEI 1447/2008). NR 184 TC 46 Z9 50 U1 3 U2 9 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD OCT PY 2012 VL 40 IS 4 BP 990 EP 1013 DI 10.1183/09031936.00000712 PG 24 WC Respiratory System SC Respiratory System GA 020FX UT WOS:000309795500029 PM 22496318 ER PT J AU Kim, DG Choi, JW Lee, JY Kim, H Oh, YS Lee, JW Tak, YK Song, JM Razin, E Yun, SH Kim, S AF Kim, Dae Gyu Choi, Jin Woo Lee, Jin Young Kim, Hyerim Oh, Young Sun Lee, Jung Weon Tak, Yu Kyung Song, Joon Myong Razin, Ehud Yun, Seok-Hyun Kim, Sunghoon TI Interaction of two translational components, lysyl-tRNA synthetase and p40/37LRP, in plasma membrane promotes laminin-dependent cell migration SO FASEB JOURNAL LA English DT Article DE metastasis; KRS; phosphorylation; 67LR ID PROTEIN-PROTEIN INTERACTIONS; GENE-EXPRESSION; UBIQUITIN LIGASES; CRYSTAL-STRUCTURE; COMPLEX-FORMATION; BINDING PROTEIN; TUMOR-CELLS; RECEPTOR; PHOSPHORYLATION; METASTASIS AB Although human lysyl-tRNA synthetase (KRS), an enzyme for protein synthesis, is often highly expressed in various cancer cells, its pathophysiological implications have not been understood. Here we found that KRS induces cancer cell migration through interaction with the 67-kDa laminin receptor (67LR) that is converted from ribosomal subunit p40. On laminin signal, KRS was phosphorylated at the T52 residue by p38MAPK and dissociated from the cytosolic multi-tRNA synthetase complex for membrane translocation. The importance of T52 phosphorylation for membrane translocation of KRS was confirmed by site-directed mutagenesis. In the membrane, turnover of 67LR was controlled by Nedd4-mediated ubiquitination, and KRS inhibited ubiquitin-dependent degradation of 67LR, thereby enhancing laminin-induced cell migration. This work thus unveiled a unique function of KRS in the control of cell migration and its pathological implication in metastasis.- Kim, D. G., Choi, J. W., Lee, J. Y., Kim, H., Oh, Y. S., Lee, J. W., Tak, Y. K., Song, J. M., Razin, E., Yun, S.-H., Kim, S. Interaction of two translational components, lysyl-tRNA synthetase and p40/37LRP, in plasma membrane promotes laminin-dependent cell migration. FASEB J. 26, 4142-4159 (2012). www.fasebj.org C1 [Kim, Dae Gyu; Choi, Jin Woo; Lee, Jin Young; Kim, Hyerim; Oh, Young Sun; Lee, Jung Weon; Tak, Yu Kyung; Song, Joon Myong; Kim, Sunghoon] Seoul Natl Univ, Med Bioconvergence Res Ctr, Seoul 151742, South Korea. [Kim, Dae Gyu; Lee, Jin Young; Lee, Jung Weon; Kim, Sunghoon] Seoul Natl Univ, Coll Pharm, Seoul 151742, South Korea. [Lee, Jung Weon; Tak, Yu Kyung; Song, Joon Myong; Kim, Sunghoon] Seoul Natl Univ, World Class Univ, Dept Mol Med & Biopharmaceut Sci, Seoul 151742, South Korea. [Razin, Ehud] Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Biochem & Mol Biol, IL-91010 Jerusalem, Israel. [Yun, Seok-Hyun] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. RP Kim, S (reprint author), Seoul Natl Univ, Med Bioconvergence Res Ctr, Seoul 151742, South Korea. EM sungkim@snu.ac.kr RI Lee, Jung Weon/F-9149-2012 FU Global Frontier grant from the National Research Foundation [NRF-M1AXA002-2010-0029785]; Acceleration Research grant from the National Research Foundation [R17-2007-020-01000-0]; 21st Frontier Functional Proteomics Research grant from the National Research Foundation [M108KM010027-08K1301-02710]; Ministry of Education, Science, and Technology of Korea FX This work was supported by Global Frontier (NRF-M1AXA002-2010-0029785), Acceleration Research (R17-2007-020-01000-0), and 21st Frontier Functional Proteomics Research (M108KM010027-08K1301-02710) grants from the National Research Foundation, funded by the Ministry of Education, Science, and Technology of Korea. NR 58 TC 26 Z9 26 U1 0 U2 6 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD OCT PY 2012 VL 26 IS 10 BP 4142 EP 4159 DI 10.1096/fj.12-207639 PG 18 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 018YM UT WOS:000309704000021 PM 22751010 ER PT J AU Golden-Mason, L Stone, AE Bambha, KM Cheng, LL Rosen, HR AF Golden-Mason, Lucy Stone, Amy E. L. Bambha, Kiran M. Cheng, Linling Rosen, Hugo R. TI Race- and gender-related variation in natural killer p46 expression associated with differential anti-hepatitis c virus immunity SO HEPATOLOGY LA English DT Article ID HUMAN NK CELLS; TOLL-LIKE RECEPTORS; DENDRITIC CELLS; CYTOTOXICITY RECEPTORS; INFLUENZA INFECTION; MEDIATED CYTOLYSIS; SURFACE EXPRESSION; VIRAL-INFECTIONS; HCV INFECTION; NKP46 AB Major racial and gender differences have been documented in the natural history and treatment responses of chronic hepatitis C virus (HCV) infection; however, distinct mechanisms have remained enigmatic. We hypothesized that racial- and gender-related differences in natural killer (NK) cell populations may explain altered natural history and treatment responses. Our study cohort consisted of 29 African-American (AA; 55% male) and 29 Caucasian-American (CA; 48% male) healthy uninfected control subjects. Multiparameter flow cytometric analysis was used to characterize levels, phenotype with respect to 14 NK receptors, and lymphokine-activated killing (LAK) function. Gene expression was assessed by real-time reverse-transcriptase polymerase chain reaction after 6-hour in vitro stimulation with Toll-like receptor (TLR) ligands. The ability to control HCV infection was assessed in the Huh-7.5/JFH-1 coculture system. NK expression of natural cytotoxicity receptor NKp46 was strongly associated with CA race and female gender and correlated positively with LAK activity (P = 0.0054). NKp46high NKs were more efficient at controlling HCV than their NKp46low counterparts (P < 0.001). Similarly, ligation of NKp46 on isolated NK cells resulted in a significant reduction in the HCV copy number detected in Huh-7.5/JFH-1 coculture (multiplicity of infection: 0.01) at an effector:target ratio of 5:1 (P < 0.005). After TLR stimulation, genes involved in cytotoxicity, but not cytokine genes, were significantly up-regulated in NKp46high NKs. Cytokine stimulation (interleukin [IL]-12 and IL-15) demonstrated that NKp46high NK cells have significantly higher interferon-gamma production than NKp46low cells. TLR stimulation significantly induced degranulation as well as tumor necrosis factor alpha (TNF-a)-related apoptosis-inducing ligand, Fas, and TNF-a protein expression in NKp46high NKs. NKp46 ligand was induced on HCV-infected hepatocytes. Conclusions: NKp46 expression may contribute to differential HCV responses. NKp46 expression correlates with anti-HCV activity in vitro and thus may prove to be a useful therapeutic target. (HEPATOLOGY 2012) C1 [Golden-Mason, Lucy; Stone, Amy E. L.; Bambha, Kiran M.; Cheng, Linling; Rosen, Hugo R.] Univ Colorado Denver, Div Gastroenterol & Hepatol, Hepatitis Ctr C, Dept Med, Aurora, CO 80045 USA. [Golden-Mason, Lucy; Stone, Amy E. L.; Rosen, Hugo R.] Univ Colorado, Integrated Program Immunol, Denver, CO 80202 USA. [Golden-Mason, Lucy; Stone, Amy E. L.; Rosen, Hugo R.] Natl Jewish Hosp, Denver, CO USA. [Rosen, Hugo R.] Denver VA Med Ctr, Denver, CO USA. RP Rosen, HR (reprint author), Univ Colorado Denver, Div Gastroenterol & Hepatol, Hepatitis Ctr C, Dept Med, B-158,Acad Off Bldg 1,12631 E 17th Ave,Room 7614,, Aurora, CO 80045 USA. EM Hugo.Rosen@UCDENVER.edu FU VA Merit Review Grant; NIH [U19 AI 1066328, K24AI083742] FX This work was supported by VA Merit Review Grant, and NIH grants U19 AI 1066328 and K24AI083742. The authors thank Dr. Takaji Wakita (National Institute of Infectious Diseases) for kindly providing the JFH-1 plasmid. The authors thank the Colorado Center for AIDS Research Laboratory Core for access to FACS sorting. NR 31 TC 26 Z9 26 U1 0 U2 28 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2012 VL 56 IS 4 BP 1214 EP 1222 DI 10.1002/hep.25771 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 018PJ UT WOS:000309673500005 PM 22505144 ER PT J AU O'Neill, SM Kueppenbender, K AF O'Neill, Siobhan M. Kueppenbender, Karsten TI Suicide in Group Therapy: Trauma and Possibility SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Article ID POSTTRAUMATIC GROWTH; GROUP-PSYCHOTHERAPY; COUNTERTRANSFERENCE; LEGACY AB This paper compares and contrasts the experiences of two different long term psychodynamic psychotherapy groups in which a patient suicided. The acute reactions and longer term process of each group is described in detail and discussed. The reactions of the two leaders, married to each other and in a shared supervisory group with the late Anne Alonso, and their own working through of the traumatic losses are explored. Their experiences highlight the importance of open discussion of the suicides in the groups, consultation with senior colleagues, and continual processing of their own reactions as a means of fostering posttraumatic growth. The authors discuss their experience in light of the literature on trauma in groups and the emerging literature on posttraumatic growth and they reflect on implications for the community of group therapists. C1 [O'Neill, Siobhan M.; Kueppenbender, Karsten] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [O'Neill, Siobhan M.; Kueppenbender, Karsten] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Kueppenbender, Karsten] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. RP O'Neill, SM (reprint author), 1130 Massachusetts Ave, Cambridge, MA 02138 USA. EM kkueppenbender@yahoo.com NR 30 TC 1 Z9 1 U1 0 U2 3 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0020-7284 J9 INT J GROUP PSYCHOTH JI Int. J. Group Psychother. PD OCT PY 2012 VL 62 IS 4 BP 587 EP 611 PG 25 WC Psychology, Clinical SC Psychology GA 018CH UT WOS:000309637100005 ER PT J AU Jones, D Duffy, ME Flanagan, J Foster, F AF Jones, Dorothy Duffy, Mary E. Flanagan, Jane Foster, Frances TI Psychometric Evaluation of the Functional Health Pattern Assessment Screening Tool (FHPAST) SO INTERNATIONAL JOURNAL OF NURSING KNOWLEDGE LA English DT Article DE Functional health pattern; instrument development; psychometric testing AB PURPOSE: To report findings of psychometric testing of the Functional Health Pattern Screening Tool (FHPAST). METHODS: Psychometric evaluation including internal consistency and principal components analysis. FINDINGS: The findings indicate that the FHPAST is a reliable, three-component, 57-item valid instrument. CONCLUSIONS: Psychometric testing supports the use of the FHPAST in research. The instrument captures each of the 11 functional health patterns as described by Gordon (1994) and has been translated into, and is available in, several languages. PRACTICE IMPLICATIONS: Continued testing and refinement is needed across populations to support the findings from this investigation and to evaluate the outcomes of patient-centered interventions over time. C1 [Jones, Dorothy; Flanagan, Jane] Boston Coll, William F Connell Sch Nursing, Chestnut Hill, MA 02167 USA. [Jones, Dorothy] Massachusetts Gen Hosp, Yvonne I Munn Ctr Nursing Res, Boston, MA 02114 USA. [Duffy, Mary E.] Boston Coll, Connell Sch Nursing, Chestnut Hill, MA 02167 USA. RP Jones, D (reprint author), Boston Coll, William F Connell Sch Nursing, Chestnut Hill, MA 02167 USA. EM jones@bc.edu NR 20 TC 3 Z9 3 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-3087 J9 INT J NURS KNOWL JI Int. J. Nurs. Knowl. PD OCT PY 2012 VL 23 IS 3 BP 140 EP 145 DI 10.1111/j.2047-3095.2012.01224.x PG 6 WC Nursing SC Nursing GA 017KJ UT WOS:000309588500004 PM 23043653 ER PT J AU Mansbach, JM Piedra, PA Borregaard, N Martineau, AR Neuman, MI Espinola, JA Camargo, CA AF Mansbach, Jonathan M. Piedra, Pedro A. Borregaard, Niels Martineau, Adrian R. Neuman, Mark I. Espinola, Janice A. Camargo, Carlos A., Jr. TI Serum cathelicidin level is associated with viral etiology and severity of bronchiolitis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID VITAMIN-D; INNATE IMMUNITY; PLASMA C1 [Mansbach, Jonathan M.; Neuman, Mark I.] Boston Childrens Hosp, Dept Med, Boston, MA USA. [Piedra, Pedro A.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Borregaard, Niels] Rigshosp, Dept Hematol, DK-2100 Copenhagen, Denmark. [Martineau, Adrian R.] Barts & London Queen Marys Sch Med & Dent, Ctr Primary Care & Publ Hlth, London, England. [Espinola, Janice A.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Mansbach, JM (reprint author), Boston Childrens Hosp, Dept Med, Boston, MA USA. EM jonathan.mansbach@childrens.harvard.edu RI Martineau, Adrian/A-3083-2010 FU NCRR NIH HHS [UL1 RR-025758, UL1 RR025758]; NIAID NIH HHS [K23 AI-77801, K23 AI077801, U01 AI-67693, U01 AI067693] NR 10 TC 9 Z9 10 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD OCT PY 2012 VL 130 IS 4 BP 1007 EP + DI 10.1016/j.jaci.2012.07.044 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA 017MT UT WOS:000309594800031 PM 22944482 ER PT J AU Thurston, RC El Khoudary, SR Sutton-Tyrrell, K Crandall, CJ Sternfeld, B Joffe, H Gold, EB Selzer, F Matthews, KA AF Thurston, Rebecca C. El Khoudary, Samar R. Sutton-Tyrrell, Kim Crandall, Carolyn J. Sternfeld, Barbara Joffe, Hadine Gold, Ellen B. Selzer, Faith Matthews, Karen A. TI Vasomotor Symptoms and Insulin Resistance in the Study of Women's Health Across the Nation SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MENOPAUSAL HOT FLASHES; CARDIAC VAGAL CONTROL; MIDDLE-AGED WOMEN; POSTMENOPAUSAL WOMEN; CARDIOVASCULAR RISK; HORMONE-THERAPY; TRANSITION; ASSOCIATION; FLUSHES; DISEASE AB Context: Emerging research suggests links between menopausal hot flashes and cardiovascular disease risk. The mechanisms underlying these associations are unclear, due to the incomplete understanding of the physiology of hot flashes. Objective and Main Outcome Measures: We examined the associations between hot flashes/night sweats and glucose and insulin resistance over 8 yr, controlling for cardiovascular risk factors and reproductive hormones. Design, Setting, and Participants: Participants in the Study of Women's Health Across the Nation (SWAN) (n = 3075), a longitudinal cohort study, were ages 42-52 yr at entry. Women completed questionnaires (hot flashes, night sweats: none, 1-5 d, >= 6 d, past 2 wk), physical measures (blood pressure, height, weight), and a fasting blood draw [serum glucose, insulin, estradiol (E2), FSH] annually for 8 yr. Hot flashes/night sweats were examined in relation to glucose and the homeostasis model assessment (HOMA) in mixed models, adjusting for demographics, cardiovascular risk factors, medications, and E2/FSH. Results: Compared to no flashes, hot flashes were associated with a higher HOMA(log) index [vs. none; hot flashes, 1-5 d: % difference (95% confidence interval), 2.37 (0.36-4.43), P = 0.02; and >= 6 d: 5.91 (3.17-8.72), P < 0.0001] in multivariable models that included body mass index. Findings persisted adjusting for E2 or FSH, and were similar for night sweats. Findings were statistically significant, yet modest in magnitude, for the outcome glucose. Conclusions: Hot flashes were associated with a higher HOMA index, an estimate of insulin resistance, and to a lesser extent higher glucose. Metabolic factors may be relevant to understanding the link between hot flashes and cardiovascular disease risk. (J Clin Endocrinol Metab 97: 3487-3494, 2012) C1 [Thurston, Rebecca C.; Matthews, Karen A.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. [Thurston, Rebecca C.; El Khoudary, Samar R.; Sutton-Tyrrell, Kim; Selzer, Faith; Matthews, Karen A.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. [Crandall, Carolyn J.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Sternfeld, Barbara] Kaiser Permanente Div Res, Oakland, CA 94612 USA. [Joffe, Hadine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Gold, Ellen B.] Univ Calif Davis, Sch Med, Dept Publ Hlth Sci, Davis, CA 95616 USA. RP Thurston, RC (reprint author), 3811 OHara St, Pittsburgh, PA 15213 USA. EM thurstonrc@upmc.edu OI El Khoudary Abushaban, Samar/0000-0003-2913-0821 FU National Institutes of Health (NIH), Department of Health and Human Services (DHHS), through the National Institute on Aging (NIA); National Institute of Nursing Research (NINR); NIH Office of Research on Women's Health (ORWH) [NR004061, AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495]; NIH [AG029216] FX SWAN has grant support from the National Institutes of Health (NIH), Department of Health and Human Services (DHHS), through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR), and the NIH Office of Research on Women's Health (ORWH) (Grants NR004061, AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, AG012495). This work was also supported by NIH grant AG029216 (to R.C.T.). NR 34 TC 28 Z9 29 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT 1 PY 2012 VL 97 IS 10 BP 3487 EP 3494 DI 10.1210/jc.2012-1410 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 018MH UT WOS:000309664400042 PM 22851488 ER PT J AU Schafer, AL Sellmeyer, DE Palermo, L Hietpas, J Eastell, R Shoback, DM Black, DM AF Schafer, Anne L. Sellmeyer, Deborah E. Palermo, Lisa Hietpas, Jean Eastell, Richard Shoback, Dolores M. Black, Dennis M. TI Six Months of Parathyroid Hormone (1-84) Administered Concurrently Versus Sequentially with Monthly Ibandronate Over Two Years: The PTH and Ibandronate Combination Study (PICS) Randomized Trial SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BONE-MINERAL DENSITY; POSTMENOPAUSAL WOMEN; OSTEOPOROSIS; ALENDRONATE; TERIPARATIDE; THERAPY; TURNOVER; MARKERS; MEN AB Context: PTH therapy improves bone mineral density (BMD) and decreases fractures in postmenopausal osteoporosis, but cost and the burden of daily injections limit its use. Objective: We evaluated two novel approaches to the use of 6 months of PTH therapy over 2 yr. Design, Setting, Participants, and Interventions: We conducted a randomized, double-blinded trial of two combinations of daily PTH(1-84) and monthly ibandronate in 44 postmenopausal women with low bone mass. Participants received either 6 months of concurrent PTH and ibandronate, followed by 18 months of ibandronate (concurrent) or two sequential courses of 3 months of PTH followed by 9 months of ibandronate (sequential) over 2 yr. Main Outcome Measures: Bone turnover markers were measured. Areal and volumetric BMD were assessed by dual-energy x-ray absorptiometry and quantitative computed tomography, respectively. Results: Over 2 yr, areal BMD at the spine and hip increased similarly in both groups, with 7.5 and 8.2% increases in spine BMD in the concurrent and sequential arms, respectively (difference -0.6%, 95% confidence interval = -3.4-2.1%). Volumetric BMD also increased similarly between groups. With concurrent therapy, mean N-propeptide of type I collagen increased 75% between baseline and month 1 and then declined. With sequential therapy, the second 3-month PTH course increased N-propeptide of type I collagen markedly (209%), although to a lesser absolute degree than the first. Conclusions: Six months of PTH(1-84), used over 2 yr with a bisphosphonate in either of our dosing regimens increased BMD substantially. Short PTH courses may provide the benefits of anabolic osteoporosis therapy with reduced burden for patients. (J Clin Endocrinol Metab 97: 3522-3529, 2012) C1 [Schafer, Anne L.; Shoback, Dolores M.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Palermo, Lisa; Hietpas, Jean; Black, Dennis M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Schafer, Anne L.; Shoback, Dolores M.] San Francisco VA Med Ctr, Endocrine Res Unit, San Francisco, CA 94121 USA. [Sellmeyer, Deborah E.] Johns Hopkins Univ, Dept Med, Baltimore, MD 21224 USA. [Eastell, Richard] Univ Sheffield, Dept Human Metab, Sheffield S10 2RX, S Yorkshire, England. RP Schafer, AL (reprint author), 4150 Clement St,111N, San Francisco, CA 94121 USA. EM anne.schafer@ucsf.edu FU Genentech, Inc.; Amgen; Novartis; Lilly; Warner Chilcott; AstraZeneca; Merck; Roche FX The PICS trial was supported by an investigator-initiated grant (to D. M. B.) from Genentech, Inc., a member of the Roche group. The sponsor was involved in study design and the decision to approve the final article, but it was not involved in the collection, analysis, or interpretation of data or in the writing of the article. Study drugs were supplied by NPS Pharmaceuticals, Inc. [PTH(1-84)], Genentech (ibandronate), and Bayer (calcium citrate and D3). Reagents for bone turnover marker assays were provided by Roche Diagnostics. The authors have full control of all primary data. Additional support was provided by the Department of Veterans Affairs, through the Research Enhancement Award Program (to A. L. S. and D. M. S.) and a Career Development Award (to A. L. S.).; A. L. S. and J.H. have nothing to disclose. D. E. S. has received research support from Amgen and Novartis. L. P. has consulted for NPS and Nycomed. R. E. has received research support from Amgen, Lilly, Warner Chilcott, and AstraZeneca and has consulted for Amgen, AstraZeneca, GSK, Medtronics, Nastech, Nestle, Fonterra Brands, Novartis, Ono Pharma, Osteologix, Pfizer, Lilly, Sanofi Aventis, Tethys, Unilever, Unipath, and Inverness Medical. D. M. S. has received research support from NPS and has consulted for Lilly. D. M. B. has received research support from Amgen, Merck, Novartis, and Roche and has consulted for Nycomed. NR 20 TC 17 Z9 17 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT 1 PY 2012 VL 97 IS 10 BP 3522 EP 3529 DI 10.1210/jc.2012-1844 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 018MH UT WOS:000309664400046 PM 22791766 ER PT J AU Moin, T Bergsneider, M Vespa, P Heaney, AP AF Moin, Tannaz Bergsneider, Marvin Vespa, Paul Heaney, Anthony P. TI Pituitary Function in Patients with Normal Pressure Hydrocephalus before and after Neurosurgical Correction SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HYPOPITUITARISM; CHILDREN AB Introduction: Little is known about pituitary function in patients with normal pressure hydrocephalus (NPH). This study evaluated pituitary function in a large series of patients awaiting neurosurgical correction for NPH. We also sought to ascertain whether surgical correction of hydrocephalus would result in improvement of any noted pituitary dysfunction. Methods: Patients with NPH referred for neurosurgical evaluation between February 2010 and January 2011 were eligible for recruitment. Pituitary endocrine evaluation including serum prolactin, free thyroid hormone, TSH, IGF-I, FSH, LH, estradiol, testosterone, cortisol, and ACTH was preformed at baseline and 1 and 3 months after surgery. Results: Of the 63 patients referred for possible NPH, 32 met study criteria, 20 could provide informed consent, and laboratory evaluation was obtainable in 16. The mean age of these patients was 62 +/- 14 yr, and 75% were men. The overall incidence of NPH-associated pituitary dysfunction was 31% (five of 16 patients) at baseline laboratory assessment. Hypogonadism was the most common type of pituitary dysfunction detected. Conclusion: NPH is associated with pituitary dysfunction, observed in a significant proportion (31%) of patients. As such, we recommend that pituitary screening should be considered in all NPH patients. In two patients with hypogonadism, surgical correction of NPH was associated with improved testosterone levels. Therefore, not all patients with NPH-associated pituitary dysfunction will require hormone replacement therapy because surgical correction may correct pituitary deficiencies in some instances. (J Clin Endocrinol Metab 97: 3545-3549, 2012) C1 [Moin, Tannaz] Vet Affairs Greater Los Angeles, Dept Med, Los Angeles, CA 90073 USA. [Moin, Tannaz] Vet Affairs Greater Los Angeles, Hlth Serv Res & Dev Ctr Excellence, Study Healthcare Provider Behav, Los Angeles, CA 90073 USA. [Moin, Tannaz; Heaney, Anthony P.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Bergsneider, Marvin; Vespa, Paul; Heaney, Anthony P.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurosurg, Los Angeles, CA 90095 USA. RP Heaney, AP (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. EM aheaney@mednet.ucla.edu FU VA Office of Academic Affiliations, Health Services Research and Development through the Health Services Fellowship Training Program, VA Greater Los Angeles [TPM 65-000] FX T.M. was an endocrinology fellow in the UCLA Department of Medicine, Division of Endocrinology, Diabetes, and Hypertension during data collection and initial analysis of this study. She completed manuscript preparation and submission as a health services research fellow supported by VA Office of Academic Affiliations, Health Services Research and Development through the Health Services Fellowship Training Program (TPM 65-000), VA Greater Los Angeles. NR 11 TC 4 Z9 4 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT 1 PY 2012 VL 97 IS 10 BP 3545 EP 3549 DI 10.1210/jc.2012-1978 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 018MH UT WOS:000309664400049 PM 22821894 ER PT J AU Kaess, BM Enserro, DM McManus, DD Xanthakis, V Chen, MH Sullivan, LM Ingram, C O'Donnell, CJ Keaney, JF Vasan, RS Glazer, NL AF Kaess, Bernhard M. Enserro, Danielle M. McManus, David D. Xanthakis, Vanessa Chen, Ming-Huei Sullivan, Lisa M. Ingram, Cheryl O'Donnell, Christoper J. Keaney, John F. Vasan, Ramachandran S. Glazer, Nicole L. TI Cardiometabolic Correlates and Heritability of Fetuin-A, Retinol-Binding Protein 4, and Fatty-Acid Binding Protein 4 in the Framingham Heart Study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INSULIN-RESISTANCE; METABOLIC SYNDROME; RETINOL-BINDING-PROTEIN-4; SERUM; ASSOCIATION; BIOMARKER; OBESITY; RISK; NULL; MICE AB Context: Fetuin-A, retinol-binding protein 4 (RBP4), and fatty-acid binding protein 4 (FABP4) are novel biomarkers that may link adiposity to insulin resistance and the metabolic syndrome (MetSyn). Objective: The aim of this study was to investigate the correlates of these three adiposity biomarkers in a large community-based sample. Design, Setting, Participants, and Outcomes: Serum concentrations of fetuin-A, RBP4, and FABP4 were assayed in 3658 participants of the Third Generation Framingham Heart Study cohort (mean age 40 yr, 54% women). We used multivariable regression to cross-sectionally relate biomarkers to insulin resistance, cardiovascular risk factors, and the MetSyn. The genetic contribution to inter-individual variation in biomarker levels was assessed using variance-components analysis. Results: All three biomarkers exhibited sexual dimorphisms (levels higher in women for fetuin-A and FABP4 but greater in men for RBP4) and were associated positively with insulin resistance assessed using the homeostasis model, with high-sensitivity C-reactive protein, and with prevalent MetSyn (P < 0.01 for all). The biomarkers showed distinct patterns of association with metabolic risk factors. RBP4 levels were correlated with body mass index only in unadjusted but not in adjusted models. None of the biomarkers were associated with prevalent diabetes in multivariable models. Circulating fetuin-A, RBP4, and FABP4 levels showed modest heritability, ranging from 15-44% (all P < 0.0001). Conclusions: In our large young- to middle-aged community-based sample, we observed that circulating levels of fetuin-A, RBP4, and FABP4 are associated with insulin resistance and with distinct components of MetSyn consistent with the multifactorial pathogenesis of metabolic dysregulation. (J Clin Endocrinol Metab 97: E1943-E1947, 2012) C1 [Glazer, Nicole L.] Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. [Kaess, Bernhard M.; O'Donnell, Christoper J.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Kaess, Bernhard M.] Univ Hosp Regensburg, Klin & Poliklin Innere Med 2, D-93042 Regensburg, Germany. [McManus, David D.; Ingram, Cheryl; Keaney, John F.] Univ Massachusetts, Sch Med, Worcester, MA 01655 USA. [Enserro, Danielle M.; Xanthakis, Vanessa; Sullivan, Lisa M.; Glazer, Nicole L.] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. [O'Donnell, Christoper J.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Glazer, NL (reprint author), Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, 801 Massachusetts Ave, Boston, MA 02118 USA. EM nlglazer@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970; Sullivan, Lisa/0000-0003-0726-7149 FU National Institutes of Health [NO1-HC 25195, R01-DK-080739-01] FX This work was supported through National Institutes of Health contract NO1-HC 25195 and R01-DK-080739-01 (to R.S.V.). NR 20 TC 25 Z9 25 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT 1 PY 2012 VL 97 IS 10 BP E1943 EP E1947 DI 10.1210/jc.2012-1458 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 018MH UT WOS:000309664400015 PM 22855337 ER PT J AU Lawson, EA Holsen, LM Santin, M Meenaghan, E Eddy, KT Becker, AE Herzog, DB Goldstein, JM Klibanski, A AF Lawson, Elizabeth A. Holsen, Laura M. Santin, McKale Meenaghan, Erinne Eddy, Kamryn T. Becker, Anne E. Herzog, David B. Goldstein, Jill M. Klibanski, Anne TI Oxytocin Secretion Is Associated with Severity of Disordered Eating Psychopathology and Insular Cortex Hypoactivation in Anorexia Nervosa SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MELANOCYTE-STIMULATING HORMONE; QUESTIONNAIRE EDE-Q; FOOD-INTAKE; PARAVENTRICULAR NUCLEUS; NEURAL CIRCUITRY; RECEPTOR GENE; WEIGHT-GAIN; BRAIN; RATS; NEURONS AB Context: Animal data suggest that oxytocin is a satiety hormone. We have demonstrated that anorexia nervosa (anorexia), a disorder characterized by food restriction, low weight, and hypoleptinemia, is associated with decreased nocturnal oxytocin secretion. We have also reported functional magnetic resonance imaging (fMRI) hypoactivation in anorexia in brain regions involved in food motivation. The relationships between oxytocin, food-motivation neurocircuitry, and disordered eating psychopathology have not been investigated in humans. Objective: The objective of the study was to determine whether the oxytocin response to feeding in anorexia differs from healthy women and to establish the relationship between oxytocin secretion and disordered eating psychopathology and food-motivation neurocircuitry. Design: This was a cross-sectional study. Setting: The study was conducted at a clinical research center. Participants: Participants included 35 women: 13 anorexia (AN), nine weight-recovered anorexia (ANWR), and 13 healthy controls (HC). Measures: Peripheral oxytocin and leptin levels were measured fasting and 30, 60, and 120 min after a standardized mixed meal. The Eating Disorder Examination-Questionnaire was used to assess disordered eating psychopathology. fMRI was performed during visual processing of food and nonfood stimuli to measure brain activation before and after the meal. Results: Mean oxytocin levels were higher in AN than HC at 60 and 120 min and lower in ANWR than HC at 0, 30, and 120 min and AN at all time points. Mean oxytocin area under the curve (AUC) was highest in AN, intermediate in HC, and lowest in ANWR. Mean leptin levels at all time points and AUC were lower in AN than HC and ANWR. Oxytocin AUC was associated with leptin AUC in ANWR and HC but not in AN. Oxytocin AUC was associated with the severity of disordered eating psychopathology in AN and ANWR, independent of leptin secretion, and was associated with between-group variance in fMRI activation in food motivation brain regions, including the hypothalamus, amygdala, hippocampus, orbitofrontal cortex, and insula. Conclusions: Oxytocin may be involved in the pathophysiology of anorexia. (J Clin Endocrinol Metab 97: E1898-E1908, 2012) C1 [Lawson, Elizabeth A.; Santin, McKale; Meenaghan, Erinne; Klibanski, Anne] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Eddy, Kamryn T.; Becker, Anne E.; Herzog, David B.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Holsen, Laura M.; Goldstein, Jill M.] Brigham & Womens Hosp, Div Womens Hlth, Boston, MA 02120 USA. [Holsen, Laura M.; Goldstein, Jill M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02120 USA. [Holsen, Laura M.; Goldstein, Jill M.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02120 USA. Harvard Univ, Sch Med, Boston, MA 02120 USA. RP Lawson, EA (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St, Boston, MA 02114 USA. EM ealawson@partners.org FU Harvard Catalyst; Harvard Clinical and Translational Science Center (National Institutes of Health) [UL1 RR025758]; National Institutes of Health Office of Research in Women's Health [K12 HD051959]; National Institutes of Health [K23 MH092560] FX This work was supported by Harvard Catalyst, The Harvard Clinical and Translational Science Center (National Institutes of Health Award UL1 RR025758); Harvard Grant K12 HD051959 from the Building Interdisciplinary Research Careers in Women's Health Program supported by the National Institutes of Health Office of Research in Women's Health; and National Institutes of Health Grant K23 MH092560. NR 46 TC 34 Z9 36 U1 1 U2 33 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT 1 PY 2012 VL 97 IS 10 BP E1898 EP E1908 DI 10.1210/jc.2012-1702 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 018MH UT WOS:000309664400009 PM 22872688 ER PT J AU Mannstadt, M Magen, D Segawa, H Stanley, T Sharma, A Sasaki, S Bergwitz, C Mounien, L Boepple, P Thorens, B Zelikovic, I Juppner, H AF Mannstadt, Michael Magen, Daniella Segawa, Hiroko Stanley, Takara Sharma, Amita Sasaki, Shohei Bergwitz, Clemens Mounien, Lourdes Boepple, Paul Thorens, Bernhard Zelikovic, Israel Jueppner, Harald TI Fanconi-Bickel Syndrome and Autosomal Recessive Proximal Tubulopathy with Hypercalciuria (ARPTH) Are Allelic Variants Caused by GLUT2 Mutations SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HEREDITARY HYPOPHOSPHATEMIC RICKETS; GLUCOSE-TRANSPORTER; VITAMIN-D; COTRANSPORTER; DEFICIENCY; SLC34A3; GENE AB Context: Many inherited disorders of calcium and phosphate homeostasis are unexplained at the molecular level. Objective: The objective of the study was to identify the molecular basis of phosphate and calcium abnormalities in two unrelated, consanguineous families. Patients: The affected members in family 1 presented with rickets due to profound urinary phosphate-wasting and hypophosphatemic rickets. In the previously reported family 2, patients presented with proximal renal tubulopathy and hypercalciuria yet normal or only mildly increased urinary phosphate excretion. Methods: Genome-wide linkage scans and direct nucleotide sequence analyses of candidate genes were performed. Transport of glucose and phosphate by glucose transporter 2 (GLUT2) was assessed using Xenopus oocytes. Renal sodium-phosphate cotransporter 2a and 2c (Npt2a and Npt2c) expressions were evaluated in transgenically rescued Glut2-null mice (tgGlut2(-/-)). Results: In both families, genetic mapping and sequence analysis of candidate genes led to the identification of two novel homozygous mutations (IVS4-2A>G and R124S, respectively) in GLUT2, the gene mutated in Fanconi-Bickel syndrome, a rare disease usually characterized by renal tubulopathy, impaired glucose homeostasis, and hepatomegaly. Xenopus oocytes expressing the [R124S] GLUT2 mutant showed a significant reduction in glucose transport, but neither wild-type nor mutant GLUT2 facilitated phosphate import or export; tgGlut2(-/-) mice demonstrated a profound reduction of Npt2c expression in the proximal renal tubules. Conclusions: Homozygous mutations in the facilitative glucose transporter GLUT2, which cause Fanconi-Bickel syndrome, can lead to very different clinical and biochemical findings that are not limited to mild proximal renal tubulopathy but can include significant hypercalciuria and highly variable degrees of urinary phosphate-wasting and hypophosphatemia, possibly because of the impaired proximal tubular expression of Npt2c. (J Clin Endocrinol Metab 97: E1978-E1986, 2012) C1 [Mannstadt, Michael; Segawa, Hiroko; Bergwitz, Clemens; Jueppner, Harald] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Stanley, Takara; Boepple, Paul] Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. [Sharma, Amita; Jueppner, Harald] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. [Magen, Daniella; Zelikovic, Israel] Rambam Hlth Care Campus, Pediat Nephrol Unit, IL-31096 Haifa, Israel. Technion Israel Inst Technol, Rappaport Fac Med, IL-31096 Haifa, Israel. Technion Israel Inst Technol, Res Inst, IL-31096 Haifa, Israel. [Mounien, Lourdes; Thorens, Bernhard] Univ Lausanne, Dept Physiol, CH-1015 Lausanne, Switzerland. [Mounien, Lourdes; Thorens, Bernhard] Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland. [Segawa, Hiroko; Sasaki, Shohei] Univ Tokushima, Grad Sch, Dept Mol Nutr, Tokushima 7708503, Japan. RP Mannstadt, M (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 1051,55 Fruit St, Boston, MA 02114 USA. EM mmannstadt@partners.org FU National Institute of Diabetes and Digestive and Kidney Disease [K08-DK081669-01, RO1-46718-19] FX This work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Disease [Grants K08-DK081669-01 (to M.M.) and RO1-46718-19 (to H.J.)]. NR 20 TC 5 Z9 5 U1 2 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT 1 PY 2012 VL 97 IS 10 BP E1978 EP E1986 DI 10.1210/jc.2012-1279 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 018MH UT WOS:000309664400019 PM 22865906 ER PT J AU Elmer, J Sajed, D AF Elmer, Jonathan Sajed, Dana TI RECTAL INTUSSUSCEPTION SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID ADULT INTUSSUSCEPTION C1 [Elmer, Jonathan] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sajed, Dana] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Elmer, J (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD OCT PY 2012 VL 43 IS 4 BP 706 EP 707 DI 10.1016/j.jemermed.2010.11.050 PG 2 WC Emergency Medicine SC Emergency Medicine GA 017FY UT WOS:000309576700050 PM 21459543 ER PT J AU Buijze, GA Prommersberger, KJ del Pino, JG Fernandez, DL Jupiter, JB AF Buijze, Geert A. Prommersberger, Karl-Josef del Pino, Juan Gonzalez Fernandez, Diego L. Jupiter, Jesse B. TI Corrective Osteotomy for Combined Intra- and Extra-articular Distal Radius Malunion SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Corrective osteotomy; distal radius; malunion; deformity ID INTERNAL-FIXATION; FRACTURES; WRIST; END; OUTCOMES; ADULTS AB Purpose This study evaluated the functional outcome of corrective osteotomy for combined intra- and extra-articular malunions of the distal radius using multiple outcome scores. Methods We evaluated 18 skeletally mature patients at an average of 78 months after corrective osteotomy for a combined intra- and extra-articular malunion of the distal part of the radius. The indication for osteotomy in all patients was the combination of an extra-articular deformity (>= 15 degrees volar or >= 10 degrees dorsal angulation or >= 3 mm radial shortening) and intra-articular incongruity of 2 mm or greater (maximum stepoff or gap), as measured on lateral and posteroanterior radiographs. The average interval from the injury to the osteotomy was 9 months. The average maximum stepoff or gap of the articular surface before surgery was 4 mm. Results All 18 patients healed uneventfully and the final articular incongruity was reduced to 2 mm or less. Final range of motion and grip strength significantly improved, averaging 89% and 84% of the uninjured side and 185% and 241% of the preoperative measures, respectively. The rate of excellent or good results was 72% according to the validated rating system Mayo Modified Wrist Score, and 89% according to the unvalidated system of Gartland and Werley. The mean Disabilities of the Arm, Shoulder, and Hand score was 11, which corresponds to mild perceived disability. Of the 18 cases, 11 normalized upper limb function. Five patients had complications; all were successfully treated. According to the rating system of Knirk and Jupiter, 4 had grade 1 and 1 had grade 2 osteoarthritis of the radiocarpal joint on radiographs. Two of those patients reported occasional mild pain. Radiographic osteoarthritis did not correlate with strength, motion, and wrist scores. Conclusions Outcomes of corrective osteotomy for combined Ultra- and extra-articular malunions were comparable to those of osteotomy for isolated intra- and extra-articular malunions. A successful corrective osteotomy for the treatment of complex intra- and extra-articular distal radius malunions can improve wrist function. (J Hand Surg 2012:37A:2041-2049. Copyright (C) 2012 by the American Society for Surgery of the Hand. All rights reserved.) Type of study/level of evidence Therapeutic IV. C1 [Buijze, Geert A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, Boston, MA 02114 USA. Rhon Klinikum, Klin Handchirurg, Bad Neustadt an der Saale, Germany. Santa Cristina Univ Hosp, Dept Orthopaed Surg, Unit Hand Surg, Madrid, Spain. Univ Bern, Lindenhof Hosp, Facharzt FMH Orthopad Chirurg & Handchirurg, Bern, Switzerland. RP Buijze, GA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM g.a.buijze@amc.nl FU Netherlands Organisation for Scientific Research (NWO) FX The authors thank Dr. E. Gonzalez-Hernandez for schematic drawings of the presented case. G.A.B thanks the Netherlands Organisation for Scientific Research (NWO) for their financial support of this research in the form of a PhD fellowship grant. NR 29 TC 4 Z9 5 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD OCT PY 2012 VL 37A IS 10 BP 2041 EP 2049 DI 10.1016/j.jhsa.2012.07.013 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 020WG UT WOS:000309846700014 PM 22939826 ER PT J AU Peacock, ZS Afshar, S Lukas, SJ Kaban, LB AF Peacock, Zachary S. Afshar, Salim Lukas, Saylan J. Kaban, Leonard B. TI Customized Repair of Fractured Mandibular Reconstruction Plates SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID ABLATIVE TUMOR SURGERY; NOTCH SENSITIVITY; TITANIUM; RESECTION; SYSTEM AB Purpose: To describe a novel technique using custom prostheses to repair fractured mandibular reconstruction plates spanning discontinuity defects. Materials and Methods: This is a retrospective case series reviewing the design, rapid manufacture, and use of a novel method to repair fractured plates. Three patients who could not undergo autogenous bone grafting procedures or replacement of the entire plate for medical or socioeconomic factors were treated by this method. Results: Three patients with fractured reconstruction plates were treated with a custom prosthesis engaging the reconstruction plate. Continuity and function were restored with a minimally invasive operation and short hospital stay. The custom prosthesis remained in place with stable occlusion in all 3 patients at a minimum of 9 months' follow-up. Conclusions: A technique using a custom prosthesis to quickly and less invasively restore continuity and function of the mandible after fracture of a reconstruction plate is described. (C) 2012 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 70:e563-e573, 2012 C1 [Peacock, Zachary S.; Kaban, Leonard B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Lukas, Saylan J.] Biomet Microfixat, Jacksonville, FL USA. RP Peacock, ZS (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Warren 1201,55 Fruit St, Boston, MA 02114 USA. EM zpeacock@partners.org NR 14 TC 4 Z9 4 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD OCT PY 2012 VL 70 IS 10 BP E563 EP E573 DI 10.1016/j.joms.2012.06.002 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 018NZ UT WOS:000309669200007 PM 22871312 ER PT J AU Urdaneta, RA Leary, J Lubelski, W Emanuel, KM Chuang, SK AF Urdaneta, Rainier A. Leary, Joseph Lubelski, William Emanuel, Kimberly M. Chuang, Sung-Kiang TI The Effect of Implant Size 5 x 8 mm on Crestal Bone Levels Around Single-Tooth Implants SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE Bone regeneration; dental implants; mandible; risk factors ID FINITE-ELEMENT-ANALYSIS; LOCKING-TAPER IMPLANTS; DENTAL IMPLANTS; EDENTULOUS PATIENTS; STRESS-DISTRIBUTION; ALVEOLAR CREST; RISK-FACTORS; PROSTHESES; DIAMETER; LENGTH AB Background: There is substantial evidence supporting the strain-induced biologic response of bone to mechanical load. Stress-related factors, such as implant size, have been associated with changes in crestal bone levels on dental implants. The purpose of this study is to evaluate the effect of an implant size, specifically 5 mm wide x 8 mm long (5 x 8), on pen-implant bone levels. Methods: A retrospective cohort study was conducted. The cohort was composed of patients who had >= 1 plateau root-form implant. Descriptive statistics, univariate and multivariate mixed-effects regression models, adjusted for multiple implants in the same patient were used to evaluate the correlation between 5 x 8 implants and other clinically relevant factors on crestal bone levels after insertion of single-tooth replacements. Results: The cohort was composed of 81 individuals who received 326 implants. The average change in crestal bone levels (AvBL) for 5 x 8 maxillary and mandibular implants after 5.9 years of follow-up were -0.36 and -0.04 mm, respectively. In contrast, AvBL for mandibular implants not measuring 5 x 8 was -0.51 mm. Of several different local and systemic factors evaluated, including 10 different implant sizes, 5 x 8 mandibular implants were found to be significantly less likely to lose bone when compared with mandibular implants not measuring 5 x 8 (P = 0.047). Conclusions: Implants measuring 5 x 8 demonstrated statistically significantly less pen-implant bone loss in the posterior mandible. This finding indicated that a specific implant size may be involved in mandibular bone preservation. However, prospective multicenter clinical trials are needed to validate these findings. J Periodontol 2012;83:1235-1244. C1 [Lubelski, William] Soft Artisans, Boston, MA USA. [Chuang, Sung-Kiang] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Chuang, Sung-Kiang] Harvard Univ, Sch Med, Boston, MA USA. RP Urdaneta, RA (reprint author), 25 Prairie Ave, Auburndale, MA 02466 USA. EM rainieru@yahoo.com NR 33 TC 6 Z9 6 U1 0 U2 6 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD OCT PY 2012 VL 83 IS 10 BP 1235 EP 1244 DI 10.1902/jop.2012.110299 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 020FG UT WOS:000309793800005 PM 22309172 ER PT J AU Colombo, APV Bennet, S Cotton, SL Goodson, JM Kent, R Haffajee, AD Socransky, SS Hasturk, H Van Dyke, TE Dewhirst, FE Paster, BJ AF Colombo, Ana Paula V. Bennet, Susan Cotton, Sean L. Goodson, J. Max Kent, Ralph Haffajee, Anne D. Socransky, Sigmund S. Hasturk, Hatice Van Dyke, Thomas E. Dewhirst, Floyd E. Paster, Bruce J. TI Impact of Periodontal Therapy on the Subgingival Microbiota of Severe Periodontitis: Comparison Between Good Responders and Individuals With Refractory Periodontitis Using the Human Oral Microbe Identification Microarray SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE Anti-infective agents; microbiology; oligonucleotide array sequence analysis ID GENERALIZED AGGRESSIVE PERIODONTITIS; SUPRAGINGIVAL PLAQUE CONTROL; LONG-TERM; MICROBIOLOGICAL PARAMETERS; BACTEROIDES-FORSYTHUS; SYSTEMIC ANTIBIOTICS; TOOTH LOSS; DISEASE; METRONIDAZOLE; PROFILES AB Background: This study compares the changes to the subgingival microbiota of individuals with "refractory" periodontitis (RP) or treatable periodontitis (good responders [GR]) before and after periodontal therapy by using the Human Oral Microbe Identification Microarray (HOMIM) analysis. Methods: Individuals with chronic periodontitis were classified as RP (n = 17) based on mean attachment loss (AL) and/or >3 sites with AL >= 2.5 mm after scaling and root planing, surgery, and systemically administered amoxicillin and metronidazole or as GR (n = 30) based on mean attachment gain and no sites with AL >= 2.5 mm after treatment. Subgingival plaque samples were taken at baseline and 15 months after treatment and analyzed for the presence of 300 species by HOMIM analysis. Significant differences in taxa before and post-therapy were sought using the Wilcoxon test. Results: The majority of species evaluated decreased in prevalence in both groups after treatment; however, only a small subset of organisms was significantly affected. Species that increased or persisted in high frequency in RP but were significantly reduced in GR included Bacteroidetes sp., Porphyromonas endodontails, Porphyromonas gingivalis, Preuotella spp., Tannerella forsythia, Dialister spp., Selenomonas spp., Catonella morbi, Eubacterium spp., Filifactor alocis, Paruimonas micra, Peptostreptococcus sp. OT113, Fusobacterium sp. OT203, Pseudoramibacter alactolyticus, Streptococcus intermedius or Streptococcus constellatus, and Shuttlesworthia satelles. In contrast, Capnocytophaga sputigena, Cardiobacterium hominis, Gemella haemolysans, Haemophilus parainfluenzae, Kingella oralis, Lautropia mirabilis, Neisseria elongata, Rothia dentocariosa, Streptococcus australis, and Veillonella spp. were more associated with therapeutic success. Conclusion: Persistence of putative and novel periodontal pathogens, as well as low prevalence of beneficial species was associated with chronic refractory periodontitis. J Periodontol 2012;83:1279-1287. C1 [Colombo, Ana Paula V.] Univ Fed Rio de Janeiro, Inst Microbiol, Dept Med Microbiol, BR-21941902 Rio De Janeiro, RJ, Brazil. [Bennet, Susan; Cotton, Sean L.; Dewhirst, Floyd E.; Paster, Bruce J.] Forsyth Inst, Dept Mol Genet, Cambridge, MA USA. [Goodson, J. Max; Hasturk, Hatice; Van Dyke, Thomas E.] Forsyth Inst, Ctr Clin & Translat Res, Dept Periodontol, Cambridge, MA USA. [Kent, Ralph] Forsyth Inst, Dept Biostat, Cambridge, MA USA. [Dewhirst, Floyd E.; Paster, Bruce J.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Colombo, APV (reprint author), Univ Fed Rio de Janeiro, Inst Microbiol Paulo de Goes, Bloco 1,Lab 12-03,Av Carlos Chagas Filho,373 Cida, BR-21941902 Rio De Janeiro, RJ, Brazil. EM apcolom-bo@micro.ufrj.br RI Inbeb, Inct/K-2317-2013 FU National Institute of Dental and Craniofacial Research [DE11443, RR025771]; National Council for Scientific and Technological Development, Brazil FX This work was supported by National Institute of Dental and Craniofacial Research Grants DE11443 and RR025771 and by National Council for Scientific and Technological Development, Brazil. The authors report no conflicts of interest related to this study. NR 47 TC 49 Z9 53 U1 2 U2 21 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD OCT PY 2012 VL 83 IS 10 BP 1279 EP 1287 DI 10.1902/jop.2012.110566 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 020FG UT WOS:000309793800010 PM 22324467 ER PT J AU Kozono, D Kang, J D'Andrea, AD AF Kozono, David Kang, Josephine D'Andrea, Alan D. TI Re: A DNA Repair Pathway-Focused Score for Prediction of Outcomes in Ovarian Cancer Treated with Platinum-Based Chemotherapy Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID BRCA2 MUTATIONS; SURVIVAL; ASSOCIATION C1 [Kozono, David; D'Andrea, Alan D.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. [Kang, Josephine] Harvard Univ, Radiat Oncol Program, Boston, MA 02115 USA. RP Kozono, D (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM dkozono@lroc.harvard.edu NR 6 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT PY 2012 VL 104 IS 19 BP 1514 EP 1515 DI 10.1093/jnci/djs364 PG 3 WC Oncology SC Oncology GA 018MZ UT WOS:000309666300010 ER PT J AU Burstein, HJ AF Burstein, Harold J. TI Assuring Access to Academic Cancer Centers SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material C1 [Burstein, Harold J.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Burstein, Harold J.] Dana Farber Canc Inst, Boston, MA USA. [Burstein, Harold J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Burstein, Harold J.] Dana Farber, Boston, MA USA. [Burstein, Harold J.] St Gallen Breast Canc Panel, St Gallen, Switzerland. RP Burstein, HJ (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD OCT PY 2012 VL 10 IS 10 BP 1177 EP 1178 PG 2 WC Oncology SC Oncology GA 021RB UT WOS:000309901900001 PM 23054871 ER PT J AU Abrahm, JL AF Abrahm, Janet L. TI Integrating Palliative Care Into Comprehensive Cancer Care SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID CELL LUNG-CANCER; COMMUNICATION-SKILLS; DISCUSSING PROGNOSIS; CLINICAL ONCOLOGY; AMERICAN SOCIETY; PHYSICIANS; LIFE; TALKING; TEAM; WANT AB While there are operational, financial, and workforce barriers to integrating oncology with palliative care, part of the problem lies in ourselves, not in our systems. First, there is oncologists' "learned helplessness" from years of practice without effective medications to manage symptoms or training in how to handle the tough communication challenges every oncologist faces. Unless they and the fellows they train have had the opportunity to work with a palliative care team, they are unlikely to be fully aware of what palliative care has to offer to their patients at the time of diagnosis, during active therapy, or after developing advanced disease, or may believe that, "I already do that." The second barrier to better integration is the compassion fatigue many oncologists develop from caring for so many years for patients who, despite the oncologists' best efforts, suffer and die. The cumulative grief oncologists experience may go unnamed and unacknowledged, contributing to this compassion fatigue and burnout, both of which inhibit the integration of oncology and palliative care. Solutions include training fellows and practicing oncologists in palliative care skills (eg, in symptom management, psychological disorders, communication), preventing and treating compassion fatigue, and enhancing collaboration with palliative care specialists in caring for patients with refractory distress at any stage of disease. As more oncologists develop these skills, process their grief, and recognize the breadth of additional expertise offered by their palliative care colleagues, palliative care will become integrated into comprehensive cancer care. (JNCCN 2012;10:1192-1198) C1 [Abrahm, Janet L.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Abrahm, Janet L.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Abrahm, Janet L.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Abrahm, JL (reprint author), Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, 450 Brookline Ave, Boston, MA 02115 USA. EM janet_abrahm@dfci.harvard.edu NR 47 TC 17 Z9 17 U1 1 U2 16 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD OCT PY 2012 VL 10 IS 10 BP 1192 EP 1198 PG 7 WC Oncology SC Oncology GA 021RB UT WOS:000309901900003 PM 23054873 ER PT J AU Anderson, KC Alsina, M Bensinger, W Biermann, JS Cohen, AD Devine, S Djulbegovic, B Faber, EA Gasparetto, C Hernandez-Ilizaliturri, F Huff, CA Kassim, A Krishnan, AY Medeiros, BC Meredith, R Raje, N Schriber, J Singhal, S Somlo, G Stockerl-Goldstein, K Treon, SP Tricot, G Weber, DM Yahalom, J Yunus, F Kumar, R Shead, DA AF Anderson, Kenneth C. Alsina, Melissa Bensinger, William Biermann, J. Sybil Cohen, Adam D. Devine, Steven Djulbegovic, Benjamin Faber, Edward A., Jr. Gasparetto, Christine Hernandez-Ilizaliturri, Francisco Huff, Carol Ann Kassim, Adetola Krishnan, Amrita Y. Medeiros, Bruno C. Meredith, Ruby Raje, Noopur Schriber, Jeffrey Singhal, Seema Somlo, George Stockerl-Goldstein, Keith Treon, Steven P. Tricot, Guido Weber, Donna M. Yahalom, Joachim Yunus, Furhan Kumar, Rashmi Shead, Dorothy A. TI Waldenstrom's Macroglobulinemia/Lymphoplasmacytic Lymphoma, Version 2.2013 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID CONSENSUS PANEL RECOMMENDATIONS; 2ND INTERNATIONAL WORKSHOP; PHASE-II TRIAL; WEEKLY BORTEZOMIB; IMMUNOGLOBULIN-M; CLINICAL-TRIAL; MACROGLOBULINEMIA; RITUXIMAB; THERAPY; IGM AB These NCCN Guidelines Insights highlight the important updates/changes specific to the management of Waldenstrom's Macroglobulinemia/Lymphoplasmacytic Lymphoma. These include the addition of regimens containing novel agents as primary and salvage therapy options, inclusion of the updated summary of response categories and criteria from the sixth international workshop on Waldenstrom's Macroglobulinemia, and a section on management of peripheral neuropathy in the accompanying discussion. (JNCCN 2012;10:1211-1218) C1 [Alsina, Melissa; Djulbegovic, Benjamin] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Bensinger, William] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA USA. [Biermann, J. Sybil] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Cohen, Adam D.] Fox Chase Canc Ctr, Philadelphia, PA USA. [Devine, Steven] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Devine, Steven] Ohio State Univ, Ctr Comprehens Canc, Solove Res Inst, Columbus, OH 43210 USA. [Faber, Edward A., Jr.] Univ Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Hernandez-Ilizaliturri, Francisco] Roswell Pk Canc Inst, Buffalo, NY USA. [Huff, Carol Ann] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Kassim, Adetola] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Krishnan, Amrita Y.; Somlo, George] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Medeiros, Bruno C.] Stanford Canc Inst, Stanford, CA USA. [Meredith, Ruby] Univ Alabama, Birmingham Comprehens Canc Ctr, Tuscaloosa, AL 35487 USA. [Raje, Noopur] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Schriber, Jeffrey; Weber, Donna M.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Singhal, Seema] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Stockerl-Goldstein, Keith] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Stockerl-Goldstein, Keith] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Tricot, Guido] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Yahalom, Joachim] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Yunus, Furhan] Univ Tennessee, St Jude Childrens Res Hosp, Inst Canc, Knoxville, TN 37996 USA. RI Djulbegovic, Benjamin/I-3661-2012 OI Djulbegovic, Benjamin/0000-0003-0671-1447 NR 32 TC 18 Z9 21 U1 0 U2 4 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD OCT PY 2012 VL 10 IS 10 BP 1211 EP 1219 PG 9 WC Oncology SC Oncology GA 021RB UT WOS:000309901900005 PM 23054875 ER PT J AU Ettinger, DS Akerley, W Borghaei, H Chang, AC Cheney, RT Chirieac, LR D'Amico, TA Demmy, TL Ganti, AKP Govindan, R Grannis, FW Horn, L Jahan, TM Jahanzeb, M Kessinger, A Komaki, R Kong, FM Kris, MG Krug, LM Lennes, IT Loo, BW Martins, R O'Malley, J Osarogiagbon, RU Otterson, GA Patel, JD Pinder-Schenck, MC Pisters, KM Reckamp, K Riely, GJ Rohren, E Swanson, SJ Wood, DE Yang, SC Hughes, M Gregory, KM AF Ettinger, David S. Akerley, Wallace Borghaei, Hossein Chang, Andrew C. Cheney, Richard T. Chirieac, Lucian R. D'Amico, Thomas A. Demmy, Todd L. Ganti, Apar Kishor P. Govindan, Ramaswamy Grannis, Frederic W., Jr. Horn, Leora Jahan, Thierry M. Jahanzeb, Mohammad Kessinger, Anne Komaki, Ritsuko Kong, Feng-Ming (Spring) Kris, Mark G. Krug, Lee M. Lennes, Inga T. Loo, Billy W., Jr. Martins, Renato O'Malley, Janis Osarogiagbon, Raymond U. Otterson, Gregory A. Patel, Jyoti D. Pinder-Schenck, Mary C. Pisters, Katherine M. Reckamp, Karen Riely, Gregory J. Rohren, Eric Swanson, Scott J. Wood, Douglas E. Yang, Stephen C. Hughes, Miranda Gregory, Kristina M. CA NCCN Non-Small Cell Lung TI Non-Small Cell Lung Cancer SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID GROWTH-FACTOR-RECEPTOR; PHASE-III TRIAL; CLINICAL-PRACTICE GUIDELINE; TYROSINE KINASE INHIBITORS; DIAGNOSED BRAIN METASTASES; BODY RADIATION-THERAPY; RESECTED STAGE-II; POSITRON-EMISSION-TOMOGRAPHY; RANDOMIZED CONTROLLED-TRIAL; ANAPLASTIC LYMPHOMA KINASE AB Most patients with non small cell lung cancer (NSCLC) are diagnosed with advanced cancer. These guidelines only include information about stage IV NSCLC. Patients with widespread metastatic disease (stage IV) are candidates for systemic therapy, clinical trials, and/or palliative treatment. The goal is to identify patients with metastatic disease before initiating aggressive treatment, thus sparing these patients from unnecessary futile treatment. If metastatic disease is discovered during surgery, then extensive surgery is often aborted. Decisions about treatment should be based on multidisciplinary discussion. (JNCCN 2012;10:1236-1271) C1 [Ettinger, David S.; Yang, Stephen C.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Akerley, Wallace] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Borghaei, Hossein] Fox Chase Canc Ctr, Philadelphia, PA USA. [Chang, Andrew C.; Kong, Feng-Ming (Spring)] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Cheney, Richard T.; Demmy, Todd L.] Roswell Pk Canc Inst, Buffalo, NY USA. [Chirieac, Lucian R.; Swanson, Scott J.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Ganti, Apar Kishor P.; Kessinger, Anne] Univ Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Govindan, Ramaswamy] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Govindan, Ramaswamy] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Grannis, Frederic W., Jr.; Reckamp, Karen] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Horn, Leora] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Jahan, Thierry M.] Univ Calif San Francisco, Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Jahanzeb, Mohammad; Osarogiagbon, Raymond U.] Univ Tennessee, St Jude Childrens Res Hosp, Inst Canc, Knoxville, TN 37996 USA. [Komaki, Ritsuko; Pisters, Katherine M.; Rohren, Eric] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Kris, Mark G.; Krug, Lee M.; Riely, Gregory J.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Lennes, Inga T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Loo, Billy W., Jr.] Stanford Canc Inst, Stanford, CA USA. [Martins, Renato; Wood, Douglas E.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Pinder-Schenck, Mary C.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Patel, Jyoti D.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Otterson, Gregory A.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Otterson, Gregory A.] Ohio State Univ, Ctr Comprehens Canc, Solove Res Inst, Columbus, OH 43210 USA. [O'Malley, Janis] Univ Alabama, Birmingham Comprehens Canc Ctr, Tuscaloosa, AL 35487 USA. RP Ettinger, DS (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. NR 234 TC 138 Z9 153 U1 2 U2 15 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD OCT PY 2012 VL 10 IS 10 BP 1236 EP 1271 PG 36 WC Oncology SC Oncology GA 021RB UT WOS:000309901900007 PM 23054877 ER PT J AU Levy, MH Adolph, MD Back, A Block, S Codada, SN Dalal, S Deshields, TL Dexter, E Dy, SM Knight, SJ Misra, S Ritchie, CS Sauer, TM Smith, T Spiegel, D Sutton, L Taylor, RM Temel, J Thomas, J Tickoo, R Urba, SG Von Roenn, JH Weems, JL Weinstein, SM Freedman-Cass, DA Bergman, MA AF Levy, Michael H. Adolph, Michael D. Back, Anthony Block, Susan Codada, Shirley N. Dalal, Shalini Deshields, Teresa L. Dexter, Elisabeth Dy, Sydney M. Knight, Sara J. Misra, Sumathi Ritchie, Christine S. Sauer, Todd M. Smith, Thomas Spiegel, David Sutton, Linda Taylor, Robert M. Temel, Jennifer Thomas, Jay Tickoo, Roma Urba, Susan G. Von Roenn, Jamie H. Weems, Joseph L. Weinstein, Sharon M. Freedman-Cass, Deborah A. Bergman, Mary Anne CA NCCN Palliative Care Panel TI Palliative Care SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID CELL LUNG-CANCER; OF-LIFE CARE; CENTRAL ANTICHOLINERGIC SYNDROME; UNREALISTIC EXPECTATIONS; SUPPORTIVE ONCOLOGY; CLINICAL ONCOLOGY; AMERICAN SOCIETY; CONTROLLED-TRIAL; PROSTATE-CANCER; DEATH RATTLE AB These guidelines were developed and updated by an interdisciplinary group of experts based on clinical experience and available scientific evidence. The goal of these guidelines is to help patients with cancer experience the best quality of life possible throughout the illness trajectory by providing guidance for the primary oncology team for symptom screening, assessment, palliative care interventions, reassessment, and afterdeath care. Palliative care should be initiated by the primary oncology team and augmented by collaboration with an interdisciplinary team of palliative care experts. (JNCCN 2012;10:1284-1309) C1 [Levy, Michael H.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Adolph, Michael D.; Taylor, Robert M.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Adolph, Michael D.; Taylor, Robert M.] Ohio State Univ, Ctr Comprehens Canc, Solove Res Inst, Columbus, OH 43210 USA. [Back, Anthony] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA USA. [Block, Susan] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Codada, Shirley N.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Dalal, Shalini] Univ Texas MD Anderson Canc Ctr, Houston, TX USA. [Deshields, Teresa L.] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Deshields, Teresa L.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA. [Dexter, Elisabeth] Roswell Pk Canc Inst, Buffalo, NY USA. [Dy, Sydney M.; Smith, Thomas] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Knight, Sara J.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Misra, Sumathi] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Ritchie, Christine S.] Univ Alabama, Birmingham Comprehens Canc Ctr, Tuscaloosa, AL 35487 USA. [Sauer, Todd M.] Univ Nebraska Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE USA. [Weinstein, Sharon M.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Weems, Joseph L.] Univ Tennessee, St Jude Childrens Res Hosp, Inst Canc, Knoxville, TN 37996 USA. [Von Roenn, Jamie H.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Urba, Susan G.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Tickoo, Roma] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Thomas, Jay] City Hope Comprehens Canc Ctr, Duarte, CA USA. [Temel, Jennifer] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Spiegel, David] Stanford Canc Inst, Stanford, CA USA. [Sutton, Linda] Duke Canc Inst, Durham, NC USA. RP Levy, MH (reprint author), Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RI Adolph, Michael/C-1155-2009; Taylor, Robert/E-4181-2011 FU Roswell Park Cancer Institute; Competitive Technologies, Inc.; National Cancer Institute; National Center for Complementary and Alternative Medicine; GW Pharma; Archstone Foundation; City of Hope Eisai Inc. FX Clinical Research Support: Roswell Park Cancer Institute, Competitive Technologies, Inc. National Cancer Institute; and National Center for Complementary and Alternative Medicine GW Pharma Archstone Foundation; City of Hope Eisai Inc. NR 99 TC 34 Z9 35 U1 1 U2 14 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD OCT PY 2012 VL 10 IS 10 BP 1284 EP 1309 PG 26 WC Oncology SC Oncology GA 021RB UT WOS:000309901900009 PM 23054879 ER PT J AU Geller, AC Balk, SJ Fisher, DE AF Geller, Alan C. Balk, Sophie J. Fisher, David E. TI Stemming the Tanning Bed Epidemic: Time for Action SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material ID UNITED-STATES; INDOOR; ADOLESCENTS; MELANOMA; EXPOSURE; CHILDREN; DEVICES; RISK; US C1 [Geller, Alan C.; Fisher, David E.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Balk, Sophie J.] Childrens Hosp Montefiore, New York, NY USA. [Balk, Sophie J.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Balk, Sophie J.] Community Based Hlth Ctr, Bronx, NY USA. [Balk, Sophie J.] Amer Acad Pediat AAP Comm, Elk Grove Village, IL USA. [Fisher, David E.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. [Fisher, David E.] Massachusetts Gen Hosp, Melanoma Ctr, Boston, MA 02114 USA. [Fisher, David E.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Fisher, David E.] Dana Farber Canc Inst, Melanoma Program, Boston, MA USA. RP Geller, AC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Cambridge, MA 02138 USA. NR 13 TC 5 Z9 5 U1 0 U2 4 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD OCT PY 2012 VL 10 IS 10 BP 1311 EP 1314 PG 4 WC Oncology SC Oncology GA 021RB UT WOS:000309901900010 PM 23054880 ER PT J AU Hasan, T AF Hasan, Tayyaba TI Using Cellular Mechanisms to Develop Effective Combinations of Photodynamic Therapy and Targeted Therapies SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID OVARIAN-CANCER; IN-VIVO; GROWTH-FACTOR; CELLS AB The bond between the research laboratory and the clinic is especially strong in the field of photomedicine. Much is learned in preclinical animal models, which is translated to the clinic for investigation, and then refinements in theory and technique are explored back in the laboratory. With many cancers becoming resistant to treatment, photodynamic therapy (PDT) offers a mechanistically distinct alternative. Studies have shown that PDT not only mitigates chemoresistance but also synergizes with chemotherapy and molecularly targeted therapies. From the world of biochemistry comes this unique look at 2 approaches to maximize the photodynamic effect through PDT combinations with targeted therapies: 1) using the molecular response after PDT to guide the selection of targeted agents and 2) preconditioning cancer cells to modulate nuclear molecular targets before PDT. (JNCCN 2012;10[Suppl 2]:S23-S26) C1 Harvard Univ, Sch Med, Wellman Ctr Photomed, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hasan, T (reprint author), Harvard Univ, Sch Med, Wellman Ctr Photomed, Massachusetts Gen Hosp, 40 Blossom St,BAR314, Boston, MA 02114 USA. EM thasan@partners.org NR 13 TC 5 Z9 5 U1 0 U2 4 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD OCT PY 2012 VL 10 SU 2 BP S23 EP S26 PG 4 WC Oncology SC Oncology GA 020ZG UT WOS:000309854500006 PM 23055209 ER PT J AU Capodanno, D Bhatt, DL Goto, S O'Donoghue, ML Moliterno, DJ Tamburino, C Angiolillo, DJ AF Capodanno, D. Bhatt, D. L. Goto, S. O'Donoghue, M. L. Moliterno, D. J. Tamburino, C. Angiolillo, D. J. TI Safety and efficacy of protease-activated receptor-1 antagonists in patients with coronary artery disease: a meta-analysis of randomized clinical trials SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE atopaxar; PAR-1 antagonists; vorapaxar ID CONTROLLED PHASE-II; PROCOAGULANT ACTIVITY; DOUBLE-BLIND; PLATELET; THROMBOSIS; CLOPIDOGREL; ATOPAXAR; ATHEROTHROMBOSIS; TOLERABILITY; GENERATION AB . Background: Thrombin receptor antagonists blocking protease-activated receptor-1 (PAR-1) on platelets represent a new class of oral antiplatelet agents for patients with atherothrombotic disease manifestations. Objectives: We investigated the safety and efficacy of PAR-1 antagonists in patients with coronary artery disease (CAD). Patients/Methods: Randomized, placebo-controlled trials of the PAR-1 antagonists atopaxar or vorapaxar in CAD patients were identified. The primary safety endpoint was the composite of Thrombolysis In Myocardial Infarction (TIMI) clinically significant bleeding. The primary efficacy endpoint was the composite of death, myocardial infarction (MI) or stroke. Results: A total of 41 647 patients from eight trials were included. PAR-1 antagonists were associated with higher risks of TIMI clinically significant (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.391.57, P < 0.001), major (OR 1.46, 95% CI 1.281.67, P < 0.001) and minor (OR 1.67, 95% CI 1.402.00, P < 0.001) bleeding than placebo in the fixed-effects model. PAR-1 antagonists reduced the composite of death, MI or stroke as compared with placebo (OR 0.87, 95% CI 0.810.92, P < 0.001), driven by a lower risk of MI (OR 0.85, 95% CI 0.780.92, P < 0.001). Conversely, PAR-1 antagonists and placebo did not differ in terms of risk of death (OR 0.99, 95% CI 0.901.09, P = 0.81) or stroke (OR 0.96, 95% CI 0.841.10, P = 0.59). Conclusions: PAR-1 antagonists decrease ischemic events in patients with CAD as compared with placebo, mainly driven by a reduction in MI, at the cost of an increased risk of clinically significant bleeding. C1 [Capodanno, D.; Angiolillo, D. J.] Univ Florida, Coll Med Jacksonville, Jacksonville, FL 32209 USA. [Capodanno, D.; Tamburino, C.] Ferrarotto Hosp, Catania, Italy. [Capodanno, D.; Tamburino, C.] ETNA Fdn, Catania, Italy. [Bhatt, D. L.] VA Boston Healthcare Syst, Boston, MA USA. [Bhatt, D. L.; O'Donoghue, M. L.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Bhatt, D. L.; O'Donoghue, M. L.] Harvard Univ, Sch Med, Boston, MA USA. [Goto, S.] Tokai Univ, Sch Med, Div Cardiol, Hiratsuka, Kanagawa 25912, Japan. [Moliterno, D. J.] Univ Kentucky, Lexington, KY USA. RP Angiolillo, DJ (reprint author), Univ Florida, Coll Med Jacksonville, 655 W 8th St, Jacksonville, FL 32209 USA. EM dominick.angiolillo@jax.ufl.edu OI TAMBURINO, Corrado/0000-0002-4940-9742; Capodanno, Davide/0000-0002-5156-7723 FU Bristol-Myers Squibb; Sanofi-Aventis; Eli Lilly; Daiichi Sankyo; Medicines Company; Portola; Novartis; Medicure; Accumetrics; Arena Pharmaceuticals; Merck; AstraZeneca; Bristol Myers Squibb; GlaxoSmithKline; Otsuka; Boston Scientific; Merck-Schering-Plough; Astra Zeneca; Eisai; Johnson Johnson; Amarin; Ethicon; Medtronic; Sanofi Aventis FX D. J. Angiolillo (corresponding author) reports honoraria for lectures from Bristol Myers Squibb, Sanofi-Aventis, Eli Lilly, Daiichi Sankyo, and Astra Zeneca, consulting fees from Bristol-Myers Squibb, Sanofi-Aventis, Eli Lilly, Daiichi Sankyo, The Medicines Company, Portola, Novartis, Medicure, Accumetrics, Arena Pharmaceuticals, Merck, and AstraZeneca, and research grants from Bristol Myers Squibb, Sanofi-Aventis, GlaxoSmithKline, Otsuka, Boston Scientific, Eli Lilly, Daiichi Sankyo, The Medicines Company, Portola, Accumetrics, Merck-Schering-Plough, Astra Zeneca, Eisai, and Johnson & Johnson. D. L. Bhatt discloses the following relationships: Advisory Board, Medscape Cardiology; Board of Directors, Boston VA Research Institute, Society of Chest Pain Centers; Chair, American Heart Association Get With The Guidelines Science Subcommittee; Honoraria from the American College of Cardiology (Editor, Clinical Trials, Cardiosource), Duke Clinical Research Institute (clinical trial steering committees), Slack Publications (Chief Medical Editor, Cardiology Today Intervention), and WebMD (CME steering committees); Senior Associate Editor, Journal of Invasive Cardiology; research grants from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Medtronic, Sanofi Aventis, The Medicines Company; and unfunded research for FlowCo, PLx Pharma, Takeda. S. Goto has received research grants and honoraria from Sanofi-aventis, Eisai, and Otsuka, and consulting fees from Merck and Eisai. M. L. O'Donoghue receives research grants from GlaxoSmithKline and Eisai, and honoraria from Eli Lilly and Daiichi Sankyo (continuing medical education only). D. J. Moliterno has received honoraria, consulting fees and research grant funding from Merck-Schering-Plough. The other authors state that they have no conflict of interest. NR 23 TC 18 Z9 18 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD OCT PY 2012 VL 10 IS 10 BP 2006 EP 2015 DI 10.1111/j.1538-7836.2012.04869.x PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 015QU UT WOS:000309461900004 PM 22845871 ER PT J AU Kaimal, AJ Kuppermann, M AF Kaimal, Anjali J. Kuppermann, Miriam TI Decision Making for Primary Cesarean Delivery: The Role of Patient and Provider Preferences SO SEMINARS IN PERINATOLOGY LA English DT Review DE cesarean delivery; patient-provider communication; shared decision making ID MATERNAL REQUEST; PREGNANT-WOMEN; VAGINAL BIRTH; HEALTH-CARE; SECTION; PHYSICIAN; LABOR; RATES; MODE; OBSTETRICIANS AB Primary cesarean delivery requires both the clinical assessment and judgment of the provider performing the procedure and the consent of the patient. The interaction between patient and provider and the relative weight and influence of patient preferences and provider recommendations may vary depending on whether a cesarean delivery is planned or unplanned, elective or indicated; understanding the range of contexts in which decision making takes place and the interplay of patient and provider factors in each of these situations is crucial to identifying ways to impact the cesarean rate that are safe and acceptable to both patients and providers. We conducted a review of the literature on patient and provider preferences and obstetrical decision making in the context of primary cesarean delivery, and offer recommendations for future research directions, including potential interventions that may impact the patient and provider factors affecting the primary cesarean rate. Semin Perinatol 36:384-389 (C) 2012 Elsevier Inc. All rights reserved. C1 [Kuppermann, Miriam] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. [Kaimal, Anjali J.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Kuppermann, Miriam] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Kuppermann, M (reprint author), Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, 3333 Calif St,Suite 335, San Francisco, CA 94143 USA. EM kuppermannm@obgyn.ucsf.edu NR 38 TC 7 Z9 8 U1 1 U2 14 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0146-0005 J9 SEMIN PERINATOL JI Semin. Perinatol. PD OCT PY 2012 VL 36 IS 5 BP 384 EP 389 DI 10.1053/j.semperi.2012.04.024 PG 6 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 017ZE UT WOS:000309628900014 PM 23009973 ER PT J AU Brett-Fleegler, M Rudolph, J Eppich, W Monuteaux, M Fleegler, E Cheng, A Simon, R AF Brett-Fleegler, Marisa Rudolph, Jenny Eppich, Walter Monuteaux, Michael Fleegler, Eric Cheng, Adam Simon, Robert TI Debriefing Assessment for Simulation in Healthcare Development and Psychometric Properties SO SIMULATION IN HEALTHCARE LA English DT Article DE Medical education; Health care education; Assessment; Debriefing; Simulation; Psychometrics; Behaviorally anchored rating scale ID ANCHORED RATING-SCALES; MEDICAL-EDUCATION; TRAINING-PROGRAM; PERFORMANCE; PEDIATRICS; FEEDBACK; SAFETY; EXPECTATIONS; TECHNOLOGY; CHECKLISTS AB Introduction: This study examined the reliability of the scores of an assessment instrument, the Debriefing Assessment for Simulation in Healthcare (DASH), in evaluating the quality of health care simulation debriefings. The secondary objective was to evaluate whether the instrument's scores demonstrate evidence of validity. Methods: Two aspects of reliability were examined, interrater reliability and internal consistency. To assess interrater reliability, intraclass correlations were calculated for 114 simulation instructors enrolled in webinar training courses in the use of the DASH. The instructors reviewed a series of 3 standardized debriefing sessions. To assess internal consistency, Cronbach alpha was calculated for this cohort. Finally, 1 measure of validity was examined by comparing the scores across 3 debriefings of different quality. Results: Intraclass correlation coefficients for the individual elements were predominantly greater than 0.6. The overall intraclass correlation coefficient for the combined elements was 0.74. Cronbach alpha was 0.89 across the webinar raters. There were statistically significant differences among the ratings for the 3 standardized debriefings (P < 0.001). Conclusions: The DASH scores showed evidence of good reliability and preliminary evidence of validity. Additional work will be needed to assess the generalizability of the DASH based on the psychometrics of DASH data from other settings. (Sim Healthcare 7:288-294, 2012) C1 [Brett-Fleegler, Marisa; Monuteaux, Michael; Fleegler, Eric] Childrens Hosp, Div Emergency Med, Boston, MA 02115 USA. [Brett-Fleegler, Marisa; Rudolph, Jenny; Monuteaux, Michael; Fleegler, Eric; Simon, Robert] Harvard Univ, Sch Med, Boston, MA USA. [Rudolph, Jenny; Simon, Robert] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Rudolph, Jenny; Simon, Robert] Ctr Med Simulat, Cambridge, MA USA. [Eppich, Walter] Northwestern Univ, Feinberg Sch Med, Div Emergency Med, Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. [Cheng, Adam] Univ Calgary, Alberta Childrens Hosp, KidSIM Aspire Simulat Res Program, Div Emergency Med, Calgary, AB, Canada. RP Brett-Fleegler, M (reprint author), Childrens Hosp, Div Emergency Med, 300 Longwood Ave, Boston, MA 02115 USA. EM marisa.brett@childrens.harvard.edu OI fleegler, eric/0000-0002-3563-6258 FU American Heart Association FX The Debriefing Assessment for Simulation in Healthcare (DASH) was developed by the Center for Medical Simulation (CMS) with no outside funding. The Examining Pediatric Resuscitation Education using Simulation and Scripting study was supported by a grant from the American Heart Association. To support reliability, DASH rater training is recommended by the developers although not required for DASH use or access to DASH documents. The CMS charges tuition for rater training sessions to defray the costs of the half-day training; this tuition yields no personal profit to authors J. R. and R. S. of the CMS. This training is 1 small component of the many educational activities of the CMS, which is a nonprofit, educational, charitable foundation. NR 64 TC 36 Z9 36 U1 6 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-2332 J9 SIMUL HEALTHC JI Simul. Healthc. PD OCT PY 2012 VL 7 IS 5 BP 288 EP 294 DI 10.1097/SIH.0b013e3182620228 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 018JM UT WOS:000309656400004 PM 22902606 ER PT J AU Blackstock, OJ Beach, MC Korthuis, PT Cohn, JA Sharp, VL Moore, RD Saha, S AF Blackstock, Oni J. Beach, Mary Catherine Korthuis, P. Todd Cohn, Jonathan A. Sharp, Victoria L. Moore, Richard D. Saha, Somnath TI HIV Providers' Perceptions of and Attitudes Toward Female Versus Male Patients SO AIDS PATIENT CARE AND STDS LA English DT Article ID INFECTED DRUG-USERS; ANTIRETROVIRAL THERAPY; UNITED-STATES; PHYSICIANS PERCEPTIONS; GENDER-DIFFERENCES; PROTEASE INHIBITORS; CARE; ADHERENCE; DISPARITIES; WOMEN AB As a first step in understanding the role that health care providers may play in observed gender disparities in HIV care in the United States, we sought to examine whether HIV providers' perceptions of and attitudes toward female and male patients differ. We used data from the Enhancing Communication to Improve HIV Outcomes (ECHO) study, a multisite, cross-sectional study focused on the role of the patient-provider relationship in disparities in HIV care conducted from October 2006 to June 2007. Using separate scales, we assessed HIV providers' perceptions about their patients (e.g., intelligence, compliance, responsibility) as well as providers' attitudes toward their patients (e.g., like, respect, frustrate). We used multivariable linear regression with generalized estimating equations to compare provider scores for female and male patients. Our sample comprised 37 HIV providers and 317 patients. Compared with male patients, HIV-infected females were less likely to be highly educated or employed, and more likely to report nonadherence to antiretroviral medications and depressive symptoms. In unadjusted and adjusted analyses, there was a significant difference in providers' perceptions of female and male patients, with providers having more negative perceptions of female patients. However, there was no significant difference in HIV providers' attitudes toward female and male patients in unadjusted or adjusted analyses. Further study is needed to elucidate the role of providers' perceptions and attitudes about female and male patients in observed gender disparities in HIV care. C1 [Blackstock, Oni J.] Montefiore Med Ctr, Albert Einstein Coll Med, Div Gen Internal Med, Dept Med, Bronx, NY 10467 USA. [Beach, Mary Catherine] Johns Hopkins Univ, Sch Med, Dept Med, Div Gen Internal Med, Baltimore, MD 21205 USA. [Korthuis, P. Todd; Saha, Somnath] Oregon Hlth & Sci Univ, Dept Med, Div Gen Internal Med & Geriatr, Portland, OR 97201 USA. [Cohn, Jonathan A.] Wayne State Univ, Sch Med, Dept Med, Div Infect Dis, Detroit, MI 48201 USA. [Sharp, Victoria L.] Columbia Univ, St Lukes Roosevelt Hosp Ctr, Ctr Comprehens Care, New York, NY USA. [Moore, Richard D.] Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis & Clin Pharmacol, Baltimore, MD 21205 USA. [Saha, Somnath] Portland VA Med Ctr, Gen Internal Med Sect, Portland, OR USA. RP Blackstock, OJ (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, Div Gen Internal Med, Dept Med, 3514 Dekalb Ave, Bronx, NY 10467 USA. EM oblackst@montefiore.org FU Health Resources Service Administration; Agency for Healthcare Research and Quality (AHRQ) [290-01-0012]; Department of Veterans Affairs; Agency for Healthcare Research and Quality [K08 HS013903-05]; Robert Wood Johnson Generalist Physician Faculty Scholars Awards; National Institutes of Health, National Institute on Drug Abuse [K23DA019809]; NIH [K24DA00432, R01DA11602, R01AA16893] FX This research was supported by a contract from the Health Resources Service Administration and the Agency for Healthcare Research and Quality (AHRQ 290-01-0012). Dr. Saha is supported by the Department of Veterans Affairs. Dr. Beach was supported by the Agency for Healthcare Research and Quality (K08 HS013903-05) and both Drs. Beach and Saha were supported by Robert Wood Johnson Generalist Physician Faculty Scholars Awards. Dr. Korthius was supported by the National Institutes of Health, National Institute on Drug Abuse (K23DA019809). Dr. Moore was supported by NIH (K24DA00432, R01DA11602, R01AA16893). The views expressed in this article are those of the authors, and no official endorsement by the Agency for Healthcare Research and Quality or the US Department of Health and Human Services is intended or should be inferred. NR 32 TC 4 Z9 4 U1 2 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD OCT PY 2012 VL 26 IS 10 BP 582 EP 588 DI 10.1089/apc.2012.0159 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 015XF UT WOS:000309479000003 PM 22978375 ER PT J AU Thames, AD Moizel, J Panos, SE Patel, SM Byrd, DA Myers, HF Wyatt, GE Hinkin, CH AF Thames, April D. Moizel, Jennifer Panos, Stella E. Patel, Sapna M. Byrd, Desiree A. Myers, Hector F. Wyatt, Gail E. Hinkin, Charles H. TI Differential Predictors of Medication Adherence in HIV: Findings from a Sample of African American and Caucasian HIV-Positive Drug-Using Adults SO AIDS PATIENT CARE AND STDS LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HEALTH-CARE-SYSTEM; COGNITIVE IMPAIRMENT; RACIAL-DIFFERENCES; INFECTED ADULTS; SOCIAL SUPPORT; SELF-EFFICACY; UNITED-STATES; VIRAL LOAD; HIV/AIDS AB Modest or even occasional nonadherence to combined antiretroviral therapy (cART) can result in adverse clinical outcomes. African Americans demonstrate lower rates of adherence than Caucasians or Latinos. Identifying factors that influence medication adherence among African Americans is a critical step toward reducing HIV/ AIDS disease progression and mortality. In a sample of 181 African American (n = 144) and Caucasian (n = 37) HIV-positive drug-using individuals [age (M = 42.31; SD = 6.6) education (M = 13.41; SD = 2.1)], we examined the influence of baseline drug use, literacy, neurocognition, depression, treatment-specific social support, and patient satisfaction with health care provider on medication adherence averaged over the course of 6 months (study dates 2002-2006). Our findings suggest differential baseline predictors of medication adherence for African Americans and Caucasians, such that patient satisfaction with provider was the strongest predictor of follow-up medication adherence for African Americans whereas for Caucasians depressive symptoms and treatment-specific social support were predictive of medication adherence (after controlling for duration of drug use). C1 [Thames, April D.; Panos, Stella E.; Patel, Sapna M.; Myers, Hector F.; Wyatt, Gail E.; Hinkin, Charles H.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Myers, Hector F.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. [Moizel, Jennifer] Alliant Int Univ Angeles, Dept Clin Psychol, Los Angeles, CA USA. [Byrd, Desiree A.] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. [Thames, April D.; Panos, Stella E.; Patel, Sapna M.; Hinkin, Charles H.] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. RP Thames, AD (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza,C8-746, Los Angeles, CA 90095 USA. EM athames@mednet.ucla.edu RI Thames, April/K-1964-2014 OI Thames, April/0000-0001-8414-7189 FU National Institute of Mental Health [RO1 MH58552, T32 19535] FX This study was funded by the National Institute of Mental Health (RO1 MH58552) awarded to Charles Hinkin, Ph.D. Dr. Thames is supported under a National Institute of Mental Health training grant (T32 19535; PI: C. Hinkin). NR 61 TC 21 Z9 21 U1 5 U2 16 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD OCT PY 2012 VL 26 IS 10 BP 621 EP 630 DI 10.1089/apc.2012.0157 PG 10 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 015XF UT WOS:000309479000007 PM 22889235 ER PT J AU Bandeali, SJ Kayani, WT Lee, VV Pan, W Elayda, MAA Nambi, V Jneid, HM Alam, M Wilson, JM Birnbaum, Y Ballantyne, CM Virani, SS AF Bandeali, Salman J. Kayani, Waleed T. Lee, Vei-Vei Pan, Wei Elayda, Mac Arthur A. Nambi, Vijay Jneid, Hani M. Alam, Mahboob Wilson, James M. Birnbaum, Yochai Ballantyne, Christie M. Virani, Salim S. TI Outcomes of Preoperative Angiotensin-Converting Enzyme Inhibitor Therapy in Patients Undergoing Isolated Coronary Artery Bypass Grafting SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ATRIAL-FIBRILLATION; CARDIAC-SURGERY; CARDIOVASCULAR-SURGERY; MYOCARDIAL-INFARCTION; RISK PATIENTS; EVENTS; SYSTEM; TRIAL; METAANALYSIS; PREVENTION AB The association between preoperative use of angiotensin-converting enzyme (ACE) inhibitors and outcomes after coronary artery bypass grafting (CABG) remain controversial. Our aim was to study in-hospital outcomes after isolated CABG in patients on preoperative ACE inhibitors. A retrospective analysis of 8,889 patients who underwent isolated CABG from 2000 through 2011 was conducted. The primary outcome of interest was the incidence of major adverse events (MAEs) defined as a composite of mortality, postoperative renal dysfunction, myocardial infarction, stroke, and atrial fibrillation during index hospitalization. The secondary outcome was the incidence of individual outcomes included in MAEs. Logistic regression analyses were performed. Of 8,889 patients, 3,983 (45%) were on preoperative ACE inhibitors and 4,906 (55%) were not. Overall incidence of MAEs was 38.1% (n = 1,518) in the ACE inhibitor group compared to 33.6% (n = 1,649) in the no-ACE inhibitor group. Preoperative use of ACE inhibitors was independently associated with MAEs (odds ratio 1.13, 95% confidence interval 1.03 to 1.24), most of which was driven by a statistically significant increase in postoperative renal dysfunction (odds ratio 1.18, 95% confidence interval 1.03 to 1.36) and atrial fibrillation (odds ratio 1.15, 95% confidence interval 1.05 to 1.27). In-hospital mortality, postoperative myocardial infarction, and stroke were not significantly associated with preoperative ACE inhibitor use. Analyses performed after excluding patients with low ejection fractions yielded similar results. In conclusion, preoperative ACE inhibitor use was associated with an increased risk of MAEs after CABG, in particular postoperative renal dysfunction and atrial fibrillation. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;110:919-923) C1 [Bandeali, Salman J.; Nambi, Vijay; Jneid, Hani M.; Birnbaum, Yochai; Ballantyne, Christie M.; Virani, Salim S.] Baylor Coll Med, Dept Med, Cardiol Sect, Houston, TX 77030 USA. [Virani, Salim S.] Hlth Serv Res & Dev Ctr Excellence, Hlth Policy & Qual Program, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. [Lee, Vei-Vei; Elayda, Mac Arthur A.] St Lukes Episcopal Hosp, Texas Heart Inst, Dept Epidemiol & Biostat, Houston, TX USA. [Wilson, James M.] St Lukes Episcopal Hosp, Texas Heart Inst, Cardiol Sect, Houston, TX USA. [Pan, Wei] Texas Heart Inst, Dept Cardiovasc Anesthesiol, Houston, TX 77025 USA. [Nambi, Vijay; Ballantyne, Christie M.; Virani, Salim S.] Baylor Coll Med, Dept Med, Sect Cardiovasc Res, Houston, TX 77030 USA. [Nambi, Vijay; Ballantyne, Christie M.; Virani, Salim S.] Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Dis Prevent, Houston, TX USA. [Jneid, Hani M.; Virani, Salim S.] Michael E DeBakey VA Med Ctr, Cardiol Sect, Dept Med, Houston, TX USA. [Alam, Mahboob] Memphis Vet Affairs Med Ctr, Cardiol Sect, Dept Med, Memphis, TN USA. RP Bandeali, SJ (reprint author), Baylor Coll Med, Dept Med, Cardiol Sect, Houston, TX 77030 USA. EM bandeali@bcm.edu OI Virani, Salim/0000-0001-9541-6954 FU Department of Veterans Affairs Health Services Research and Development Service Career Development Award FX Dr. Virani is supported by a Department of Veterans Affairs Health Services Research and Development Service Career Development Award. NR 28 TC 17 Z9 17 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 1 PY 2012 VL 110 IS 7 BP 919 EP 923 DI 10.1016/j.amjcard.2012.05.021 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015ZO UT WOS:000309487100001 PM 22727178 ER PT J AU Yonetsu, T Kim, JS Kato, K Kim, SJ Xing, L Yeh, RW Sakhuja, R McNulty, I Lee, H Zhang, SS Uemura, S Yu, B Kakuta, T Jang, IK AF Yonetsu, Taishi Kim, Jung-Sun Kato, Koji Kim, Soo-Joong Xing, Lei Yeh, Robert W. Sakhuja, Rahul McNulty, Iris Lee, Hang Zhang, Shaosong Uemura, Shiro Yu, Bo Kakuta, Tsunekazu Jang, Ik-Kyung TI Comparison of Incidence and Time Course of Neoatherosclerosis Between Bare Metal Stents and Drug-Eluting Stents Using Optical Coherence Tomography SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ATHEROSCLEROTIC PLAQUES; IMPLANTATION; NEOVASCULARIZATION; RESTENOSIS; LESIONS AB Recent studies have reported the development of neoatherosclerosis inside stents and subsequent acute coronary syndrome secondary to disruption of neointimal hyperplasia. The aim of the study was to compare the characteristics of neointimal hyperplasia and its time course between bare metal stents (BMSs) and drug-eluting stents (DESs) using optical coherence tomography. A total of 138 stents were divided into 3 groups according to the follow-up period: early phase, <9 months (25 BMSs and 27 DESs); intermediate phase, >= 9 and <48 months (18 BMSs and 43 DESs); and delayed phase, >= 48 months (13 BMSs and 12 DESs). Optical coherence tomographic analysis included the presence of lipid-laden intima, percentage of lipid-rich plaque, and signal attenuation. The optical coherence tomographic findings were compared between the BMSs and DESs in each period, and the difference between the periods was also determined. In the early phase, a greater incidence of lipid-laden plaque (37% vs 8%, p = 0.02) and a greater percentage of lipid-rich plaque (12.9 +/- 25.1% vs 1.2 +/- 4.3%, p = 0.01) were found in the DESs than in the BMSs. In the intermediate phase, the DES group continuously showed a significantly greater incidence of lipid-laden plaque (63% vs 28%, p = 0.03) and greater percentage of lipid-rich plaque (24.8 +/- 28.1% vs 4.1 +/- 7.3%, p < 0.01). In addition, signal attenuation was greater in the DES group, suggesting early changes in neointimal hyperplasia properties. In the delayed phase, lipid-laden plaque was the predominant type in both groups. In conclusion, lipid-rich neoatherosclerosis develops inside stents earlier in DESs than in BMSs. After 48 months, most restenotic stents will have developed lipid-laden neointima in both groups. (C) 2012 Published by Elsevier Inc. (Am J Cardiol 2012;110: 933-939) C1 [Yonetsu, Taishi; Kato, Koji; Kim, Soo-Joong; Yeh, Robert W.; McNulty, Iris; Jang, Ik-Kyung] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Yonetsu, Taishi; Kato, Koji; Kim, Soo-Joong; Yeh, Robert W.; McNulty, Iris; Jang, Ik-Kyung] Harvard Univ, Sch Med, Boston, MA USA. [Lee, Hang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA USA. [Kim, Jung-Sun] Yonsei Univ, Coll Med, Seoul, South Korea. [Kim, Jung-Sun] Severance Hosp, Div Cardiol, Dept Internal Med, Seoul, South Korea. [Kim, Soo-Joong] Kyung Hee Univ, Div Cardiol, Coll Med, Seoul, South Korea. [Xing, Lei; Yu, Bo] Harbin Med Univ, Dept Cardiol, Affiliated Hosp 2, Key Labs,Educ Minist Myocardial Ischemia Mech & T, Harbin, Peoples R China. [Sakhuja, Rahul] Wellmont CVA Heart Inst, Div Cardiovasc Med Intervent & Struct Heart Dis, Kingsport, TN USA. [Uemura, Shiro] Nara Med Univ, Dept Med 1, Nara, Japan. [Kakuta, Tsunekazu] Tsuchiura Kyodo Gen Hosp, Div Cardiol, Ibaraki, Japan. [Zhang, Shaosong] LightLab Imaging, Westford, MA USA. [Zhang, Shaosong] Harbin Med Univ, Harbin, Peoples R China. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. EM ijang@partners.org FU St. Jude Medical (St. Paul, Minnesota); Division of Cardiology, Massachusetts General Hospital (Boston, Massachusetts); Light Lab Imaging (Westford, Massachusetts)/St. Jude Medical (St. Paul, Minnesota) FX This study was supported by research grants from St. Jude Medical (St. Paul, Minnesota), Division of Cardiology, Massachusetts General Hospital (Boston, Massachusetts), and Dr. John Nam.; Dr. Jang received a research grant and consulting fee from Light Lab Imaging (Westford, Massachusetts)/St. Jude Medical (St. Paul, Minnesota) and Dr. Zhang is an employee of Light Lab Imaging (Westford, Massachusetts)/St. Jude Medical (St. Paul, Minnesota). NR 19 TC 36 Z9 40 U1 0 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 1 PY 2012 VL 110 IS 7 BP 933 EP 939 DI 10.1016/j.amjcard.2012.05.027 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 015ZO UT WOS:000309487100003 PM 22727183 ER PT J AU Tran, TT Beyda, ND Biehle, LR Cottreau, JE Echevarria, K Musick, WL Perez, KK Schilling, AN AF Tran, Truc T. Beyda, Nicholas D. Biehle, Lauren R. Cottreau, Jessica E. Echevarria, Kelly Musick, William L. Perez, Katherine K. Schilling, Amy N. CA Houston Infect Dis Network TI Significant publications on infectious diseases pharmacotherapy in 2011 SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; CLOSTRIDIUM-DIFFICILE INFECTION; HEPATITIS-C VIRUS; CLINICAL-PRACTICE GUIDELINES; MINIMUM INHIBITORY CONCENTRATION; BLOOD-STREAM INFECTIONS; GENOTYPE 1 INFECTION; ACUTE OTITIS-MEDIA; DOUBLE-BLIND; NAIVE ADULTS AB Purpose. Important articles on topics pertinent to infectious diseases (ID) pharmacotherapy published in prominent peer-reviewed journals in 2011 are summarized. Summary. Pharmacists, physicians, and researchers from the Houston Infectious Diseases Network were asked to nominate articles published in 2011 that they perceived as having a significant impact on the field of ID pharmacotherapy. The resulting list, comprising 10 articles related to human immunodeficiency virus (HIV) disease or acquired immune deficiency syndrome (AIDS) and 38 articles on a broad range of other ID-related topics, was sent to members of the Society of Infectious Diseases Pharmacists (SIDP) for evaluation via an Internet survey. The survey participants were asked to select 10 articles from the list of general ID articles and 1 article from the HIV- or AIDS-related articles that they viewed as having the most impact on the field. Of the 328 SIDP members surveyed, 120 (37%) ranked the non-HIV-related papers and 55 (17%) ranked the HIV-related papers. The 12 highest-ranked items-including 3 guidelines-are summarized here. Conclusion. Due to the increasing number of articles published each year, it is difficult to maintain a current knowledge of significant publications in the field of ID pharmacotherapy. This review of the key articles in 2011 may be helpful to the nonspecialist clinician by lessening this burden. Am J Health-Syst Pharm. 2012; 69:1671-81 C1 [Musick, William L.; Perez, Katherine K.] Methodist Hosp, Dept Pharm, Houston, TX 77030 USA. [Tran, Truc T.; Beyda, Nicholas D.; Biehle, Lauren R.; Cottreau, Jessica E.] Univ Houston, Coll Pharm, Dept Clin Sci & Adm, Houston, TX 77030 USA. [Biehle, Lauren R.] Cardinal Hlth, Houston, TX USA. [Echevarria, Kelly] S Texas Vet Hlth Care Syst, Dept Pharm, San Antonio, TX USA. [Schilling, Amy N.] Univ Texas Galveston, Med Branch, Galveston, TX 77550 USA. RP Musick, WL (reprint author), Methodist Hosp, Dept Pharm, 6565 Fannin St,MB1-09, Houston, TX 77030 USA. EM wmusick@tmhs.org NR 78 TC 2 Z9 2 U1 0 U2 2 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD OCT 1 PY 2012 VL 69 IS 19 BP 1671 EP 1681 DI 10.2146/ajhp120151 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 015ZF UT WOS:000309486200015 PM 22997121 ER PT J AU Tai, HC Serrano-Pozo, A Hashimoto, T Frosch, MP Spires-Jones, TL Hyman, BT AF Tai, Hwan-Ching Serrano-Pozo, Alberto Hashimoto, Tadafumi Frosch, Matthew P. Spires-Jones, Tara L. Hyman, Bradley T. TI The Synaptic Accumulation of Hyperphosphorylated Tau Oligomers in Alzheimer Disease Is Associated With Dysfunction of the Ubiquitin-Proteasome System SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID PAIRED HELICAL FILAMENTS; AMYLOID-BETA; HIPPOCAMPAL-NEURONS; PROTEIN-DEGRADATION; DENDRITIC SPINES; AGGREGATION; PATHOLOGY; BRAIN; NEURODEGENERATION; COLOCALIZATION AB In Alzheimer disease (AD), deposition of neurofibrillary tangles and loss of synapses in the neocortex and limbic system each correlate strongly with cognitive impairment. Tangles are composed of misfolded hyperphosphorylated tau proteins; however, the link between tau abnormalities and synaptic dysfunction remains unclear. We examined the location of tau in control and AD cortices using biochemical and morphologic methods. We found that, in addition to its well-described axonal localization, normal tau is present at both presynaptic and postsynaptic terminals in control human brains. In AD, tau becomes hyperphosphorylated and misfolded at both presynaptic and postsynaptic terminals, and this abnormally posttranslationally modified tau is enriched in synaptoneurosomal fractions. Synaptic tau seems to be hyperphosphorylated and ubiquitinated, and forms stable oligomers resistant to SDS denaturation. The accumulation of hyperphosphorylated tau oligomers at human AD synapses is associated with increased ubiquitinated substrates and increased proteasome components, consistent with dysfunction of the ubiquitin-proteasome system. Our findings suggest that synaptic hyperphosphorylated tau oligomers may be an important mediator of the proteotoxicity that disrupts synapses in AD. (Am J Pathol 2012, 181:1426-1435; http://dx.doi.org/10.1016/j.ajpath.2012.06.033) C1 [Tai, Hwan-Ching; Serrano-Pozo, Alberto; Hashimoto, Tadafumi; Spires-Jones, Tara L.; Hyman, Bradley T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MassGen Inst Neurodegenerat Dis, Boston, MA USA. [Frosch, Matthew P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, CS Kubik Lab Neuropathol, Boston, MA USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, 114 16th St, Charlestown, MA 02129 USA. EM bhyman@partners.org RI Hashimoto, Tadafumi/A-7723-2013; SERRANO-POZO, ALBERTO/F-5119-2013; OI Spires-Jones, Tara/0000-0003-2530-0598; TAI, HWAN-CHING/0000-0003-0668-9163; SERRANO-POZO, ALBERTO/0000-0003-0899-7530 FU Alzheimer Research Fellowship from the American Health Assistance Foundation; Fundacion Alfonso Martin Escudero (Madrid, Spain); NIH [AG033670, AG08487, P50 AG005134] FX Supported by an Alzheimer Research Fellowship from the American Health Assistance Foundation (H.C.T.); Fundacion Alfonso Martin Escudero (Madrid, Spain) (A.S.P.); and grants AG033670 (T.S.J.), and AG08487 and P50 AG005134 from NIH (B.T.H.). NR 47 TC 100 Z9 102 U1 1 U2 23 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 2012 VL 181 IS 4 BP 1426 EP 1435 DI 10.1016/j.ajpath.2012.06.033 PG 10 WC Pathology SC Pathology GA 017DK UT WOS:000309570100032 PM 22867711 ER PT J AU Ravenell, RL Kamen, DL Spence, JD Hollis, BW Fleury, TJ Janech, MG Almeida, JS Shaftman, SR Oates, JC AF Ravenell, Roneka L. Kamen, Diane L. Spence, J. David Hollis, Bruce W. Fleury, Thomas J. Janech, Michael G. Almeida, Jonas S. Shaftman, Stephanie R. Oates, Jim C. TI Premature Atherosclerosis Is Associated With Hypovitaminosis D and Angiotensin-Converting Enzyme Inhibitor Non-use in Lupus Patients SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Systemic lupus erythematosus; Atherosclerosis; Vitamin D deficiency; Angiotensin-converting enzyme inhibitors; Hypercholesterolemia ID CORONARY-ARTERY-DISEASE; CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; CAROTID PLAQUE; RISK-FACTORS; VITAMIN-D; ERYTHEMATOSUS; 25-HYDROXYVITAMIN-D; PREVALENCE; ULTRASOUND AB The ultimate goal is to identify and target modifiable risk factors that will reduce major cardiovascular events in African American lupus patients. As a first step toward achieving this goal, this study was designed to explore risk factor models of preclinical atherosclerosis in a predominantly African American group of patients with systemic lupus erythematosus (SLE) using variables historically associated with endothelial function in nonlupus populations. Fifty-one subjects with SLE but without a history of clinical cardiovascular events were enrolled. At entry, a Framingham risk factor history and medication list were recorded. Sera and plasma samples were analyzed for lipids, lupus activity markers and total 25-hydroxyvitamin D (25 (OH)D levels. Carotid ultrasound measurements were performed to determine total plaque area (TPA) in both carotids. Cases had TPA values above age-matched controls from a vascular prevention clinic population. Logistic regression and machine learning analyses were performed to create predictive models. 25(OH) D levels were significantly lower, and SLE disease duration was significantly higher in cases. 25(OH) D levels inversely correlated with age-adjusted TPA. Angiotensin-converting enzyme (ACE) inhibitor nonuse associated with case status. Logistic regression models containing ACE inhibitor use, 25(OH) D levels and low-density lipoprotein levels had a diagnostic accuracy of 84% for predicting accelerated atherosclerosis. Similar results were obtained with machine learning models, but hydroxychloroquine use associated with controls in these models. This is the first study to demonstrate an association between atherosclerotic burden and 25(OH) D insufficiency or ACE inhibitor nonuse in lupus patients. These findings provide strong rationale for the study of ACE inhibitors and vitamin D replenishment as preventive therapies in this high-risk population. C1 [Ravenell, Roneka L.; Kamen, Diane L.; Fleury, Thomas J.; Oates, Jim C.] Med Univ S Carolina, Dept Med, Div Rheumatol, Charleston, SC 29425 USA. [Spence, J. David] Univ Western Ontario, Robarts Res Inst, Stroke Prevent & Atherosclerosis Res Ctr, London, ON, Canada. [Hollis, Bruce W.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Janech, Michael G.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Almeida, Jonas S.] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA. [Shaftman, Stephanie R.] Med Univ S Carolina, Dept Med, Div Biostat & Epidemiol, Charleston, SC 29425 USA. [Oates, Jim C.] Ralph H Johnson VA Med Ctr, Med Serv, Charleston, SC USA. RP Oates, JC (reprint author), Med Univ S Carolina, Dept Med, Div Rheumatol, Clin Sci Bldg,Suite 912,MSC 637, Charleston, SC 29425 USA. EM oatesjc@musc.edu RI Spence, J. David/K-6396-2013; OI Spence, J. David/0000-0001-7478-1098; Janech, Michael/0000-0002-3202-4811 FU NIH/NCRR MUSC-SCTR [UL1 RR029882]; NIH/NIAMS [K23 AR052364]; MUSC General and Clinical Research Center [M01RR001070]; VA Research Enhancement Award Program; Lupus Foundation FX This study was supported by NIH/NCRR MUSC-SCTR grant number UL1 RR029882, NIH/NIAMS grant number K23 AR052364 and the MUSC General and Clinical Research Center (M01RR001070). This study was also supported by an award from the VA Research Enhancement Award Program and a grant from the Lupus Foundation. NR 31 TC 24 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD OCT PY 2012 VL 344 IS 4 BP 268 EP 273 DI 10.1097/MAJ.0b013e31823fa7d9 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 016UL UT WOS:000309544900004 PM 22222338 ER PT J AU Wagner, SL Tanzi, RE Mobley, WC Galasko, D AF Wagner, Steven L. Tanzi, Rudolph E. Mobley, William C. Galasko, Douglas TI Potential Use of gamma-Secretase Modulators in the Treatment of Alzheimer Disease SO ARCHIVES OF NEUROLOGY LA English DT Article AB Although significant progress has occurred in the past 20 years regarding our understanding of Alzheimer disease pathogenesis, we have yet to identify disease-modifying therapeutics capable of substantially altering the clinical course of this prevalent neurodegenerative disease. In this short review, we discuss 2 approaches that are currently being tested clinically (gamma-secretase inhibition and gamma-secretase modulation) and emphasize the significant differences between these 2 therapeutic approaches. We also discuss certain genetic- and biomarker-based translational and clinical trial paradigms that may assist in developing a useful therapeutic agent. Arch Neurol. 2012;69(10):1255-1258. Published online July 16, 2012. doi:10.1001/archneurol.2012.540 C1 [Wagner, Steven L.; Mobley, William C.; Galasko, Douglas] Univ Calif San Diego, Sch Med, Dept Neurosci, La Jolla, CA 92093 USA. [Tanzi, Rudolph E.] Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, Charlestown, MA USA. RP Wagner, SL (reprint author), Univ Calif San Diego, Sch Med, Dept Neurosci, MTF 150,9500 Gilman Dr,Ste 0624, La Jolla, CA 92093 USA. EM slwagner@ucsd.edu FU NIA NIH HHS [R21 AG047484]; NINDS NIH HHS [U01 NS074501] NR 9 TC 12 Z9 12 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD OCT PY 2012 VL 69 IS 10 BP 1255 EP 1258 DI 10.1001/archneurol.2012.540 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 016TC UT WOS:000309541400003 PM 22801784 ER PT J AU Jun, G Vardarajan, BN Buros, J Yu, CE Hawk, MV Dombroski, BA Crane, PK Larson, EB Mayeux, R Haines, JL Lunetta, KL Pericak-Vance, MA Schellenberg, GD Farrer, LA AF Jun, Gyungah Vardarajan, Badri N. Buros, Jacqueline Yu, Chang-En Hawk, Michele V. Dombroski, Beth A. Crane, Paul K. Larson, Eric B. Mayeux, Richard Haines, Jonathan L. Lunetta, Kathryn L. Pericak-Vance, Margaret A. Schellenberg, Gerard D. Farrer, Lindsay A. CA Alzheimers Dis Genetics Consortium TI Comprehensive Search for Alzheimer Disease Susceptibility Loci in the APOE Region SO ARCHIVES OF NEUROLOGY LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; GENOME-WIDE ASSOCIATION; HUMAN APOLIPOPROTEIN-E; GENETIC ASSOCIATION; COMMON VARIANTS; TOMM40; ALLELE; RISK; AGE; METAANALYSIS AB Objective: To evaluate the association of risk and age at onset (AAO) of Alzheimer disease (AD) with single-nucleotide polymorphisms (SNPs) in the chromosome 19 region including apolipoprotein E (APOE) and a repeat-length polymorphism in TOMM40 (poly-T, rs10524523). Design: Conditional logistic regression models and survival analysis. Setting: Fifteen genome-wide association study data sets assembled by the Alzheimer's Disease Genetics Consortium. Participants: Eleven thousand eight hundred forty AD cases and 10 931 cognitively normal elderly controls. Main Outcome Measures: Association of AD risk and AAO with genotyped and imputed SNPs located in an 800-Mb region including APOE in the entire Alzheimer's Disease Genetics Consortium data set and with the TOMM40 poly-T marker genotyped in a subset of 1256 cases and 1605 controls. Results: In models adjusting for APOE epsilon 4, no SNPs in the entire region were significantly associated with AAO at P < .001. Rs10524523 was not significantly associated with AD or AAO in models adjusting for APOE genotype or within the subset of epsilon 3/epsilon 3 subjects. Conclusions: APOE alleles epsilon 2, epsilon 3, and epsilon 4 account for essentially all the inherited risk of AD associated with this region. Other variants including a poly-T track in TOMM40 are not independent risk or AAO loci. C1 [Jun, Gyungah; Vardarajan, Badri N.; Buros, Jacqueline; Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Med Biomed Genet, Boston, MA 02118 USA. [Jun, Gyungah; Lunetta, Kathryn L.; Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA. [Jun, Gyungah; Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02118 USA. [Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Jun, Gyungah; Vardarajan, Badri N.; Buros, Jacqueline; Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Med Biomed Genet, Boston, MA USA. [Jun, Gyungah; Lunetta, Kathryn L.; Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Jun, Gyungah; Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Ophthalmol, Boston, MA USA. [Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Neurol, Boston, MA USA. [Yu, Chang-En; Crane, Paul K.; Larson, Eric B.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Yu, Chang-En] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Larson, Eric B.] Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA. [Hawk, Michele V.; Dombroski, Beth A.; Schellenberg, Gerard D.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Mayeux, Richard] Columbia Univ, Gertrude H Sergievsky Ctr, New York, NY 10027 USA. [Mayeux, Richard] Columbia Univ, Dept Neurol, Taub Inst Alzheimers Dis & Aging Brain, New York, NY USA. [Haines, Jonathan L.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. [Haines, Jonathan L.] Vanderbilt Univ, Vanderbilt Ctr Human Genet Res, Nashville, TN USA. [Pericak-Vance, Margaret A.] Univ Miami, John P Hussman Inst Human Genom, Miami, FL USA. [Pericak-Vance, Margaret A.] Univ Miami, Dr John T Macdonald Fdn, Dept Human Genet, Miami, FL USA. RP Farrer, LA (reprint author), 72 E Concord St, Boston, MA 02118 USA. EM farrer@bu.edu RI Haines, Jonathan/C-3374-2012; Myers, Amanda/B-1796-2010; Kowall, Neil/G-6364-2012; Saykin, Andrew/A-1318-2007; Crane, Paul/C-8623-2014; Tsuang, Debby/L-7234-2016; OI Myers, Amanda/0000-0002-3100-9396; Kowall, Neil/0000-0002-6624-0213; Saykin, Andrew/0000-0002-1376-8532; Tsuang, Debby/0000-0002-4716-1894; Valladares, Otto/0000-0001-8055-2187; Farrer, Lindsay/0000-0001-5533-4225; Reisberg, Barry/0000-0002-9104-7423; Buros, Jacqueline/0000-0001-9588-4889; Crane, Paul/0000-0003-4278-7465; Ferris, Steven/0000-0001-8641-6223 FU GlaxoSmithKline; Kronos Science; Northern California Institute for Research and Education; Abbott; AstraZeneca AB; Bayer Schering Pharma AG; Bristol-Myers Squibb; Eisai Global Clinical Development; Elan Corporation; Genentech; GE Healthcare; Innogenetics; Johnson Johnson; Eli Lilly and Co; Medpace Inc; Merck and Co Inc; Novartis AG; Pfizer Inc; F. Hoffman-La Roche; Schering-Plough; Synarc Inc.; National Institutes of Health NIA; National Institutes of Health NIA through ADGC [U01 AG032984, RC2 AG036528]; National Institutes of Health NIA through National Alzheimer's Coordinating Center [U01 AG016976]; National Institutes of Health NIA through National Cell Repository for Alzheimer's Disease [U24 AG021886]; National Institutes of Health NIA through NIA Late-Onset Alzheimer's Disease Study [U24 AG026395, U24 AG026390]; National Institutes of Health NIA through Banner Sun Health Research Institute [P30 AG019610]; National Institutes of Health NIA through Boston University [P30 AG013846, U01 AG10483, R01 CA129769, R01 MH080295, R01 AG017173, R01 AG025259, R01 AG33193]; National Institutes of Health NIA through Columbia University [P50 AG008702, R37 AG015473]; National Institutes of Health NIA through Duke University [P30 AG028377, R01 AG05128, R01 NS39764, R01 MH60451]; National Institutes of Health NIA through Emory University [AG025688]; National Institutes of Health NIA through Group Health Research Institute [UO1 AG06781, UO1 HG004610]; National Institutes of Health NIA through Indiana University [P30 AG10133]; National Institutes of Health NIA through Johns Hopkins University [P50 AG005146, R01 AG020688]; National Institutes of Health NIA through Massachusetts General Hospital [P50 AG005134]; National Institutes of Health NIA through Mayo Clinic [P50 AG016574]; National Institutes of Health NIA through Mount Sinai School of Medicine [P50 AG005138, P01 AG002219]; National Institutes of Health NIA through New York University [P30 AG08051, MO1 RR00096, UL1 RR029893]; National Institutes of Health NIA through Northwestern University [P30 AG013854]; National Institutes of Health NIA through Oregon Health & Science University [P30 AG008017, R01 AG026916]; National Institutes of Health NIA through Rush University [P30 AG010161, R01 AG019085, R01 AG15819, R01 AG17917, R01 AG30146]; National Institutes of Health NIA through Translational Genomics Research Institute [R01 NS059873, R01 AG034504]; National Institutes of Health NIA through University of Alabama at Birmingham [P50 AG016582, UL1 RR02777]; National Institutes of Health NIA through University of Arizona [R01 AG031581]; National Institutes of Health NIA through University of California, Davis [P30 AG010129]; National Institutes of Health NIA through University of California, Irvine [P50 AG016573, P50 AG016575, P50 AG016576, P50 AG016577]; National Institutes of Health NIA through University of California, Los Angeles [P50 AG016570]; National Institutes of Health NIA through University of California, San Diego [P50 AG005131]; National Institutes of Health NIA through University of California, San Francisco [P50 AG023501, P01 AG019724]; National Institutes of Health NIA through University of Kentucky [P30 AG028383, AG05144]; National Institutes of Health NIA through University of Michigan [P50 AG008671]; National Institutes of Health NIA through University of Pennsylvania [P30 AG010124]; National Institutes of Health NIA through University of Pittsburgh [P50 AG005133, AG030653]; National Institutes of Health NIA through University of Southern California [P50 AG005142]; National Institutes of Health NIA through University of Texas Southwestern [P30 AG012300]; National Institutes of Health NIA through University of Miami [R01 AG027944, AG010491, AG027944, AG021547, AG019757]; National Institutes of Health NIA through University of Washington [P50 AG005136]; National Institutes of Health NIA through Vanderbilt University [R01 AG019085]; National Institutes of Health NIA through Washington University [P50 AG005681, P01 AG03991]; NIA [U24 AG21886, U01 AG024904, RC2 AG036535, K01 AG030514]; Banner Alzheimer's Foundation; Johnnie B. Byrd Sr Alzheimer's Center & Research Institute; Medical Research Council; state of Arizona; local National Health Service trusts; Newcastle University; Higher Education Funding Council for England; Alzheimer's Research Trust; BRACE; North Bristol NHS Trust Research and Innovation Department; DeNDRoN; Stichting MS Research; BrainNet Europe; Hersenstichting Nederland Breinbrekend Werk; International Parkinson Fonds; Internationale Stiching Alzheimer Onderzoek; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Dana Foundation; National Institute of Biomedical Imaging and Bioengineering; Alzheimer's Association [IIRG-08-89720, IIRG-05-14147]; US Department of Veterans Affairs Administration; Office of Research and Development; Biomedical Laboratory Research Program; Wellcome Trust; Howard Hughes Medical Institute; Canadian Institute of Health Research FX The Kathleen Price Bryan Brain Bank at Duke University Medical Center is funded by GlaxoSmithKline. Genotyping of the Translational Genomics Research Institute series 2 cohort was supported by Kronos Science. Funding for ADNI is through the Northern California Institute for Research and Education by grants from Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson & Johnson, Eli Lilly and Co, Medpace Inc, Merck and Co Inc, Novartis AG, Pfizer Inc, F. Hoffman-La Roche, Schering-Plough, and Synarc Inc.; The National Institutes of Health NIA supported this work through the following grants: ADGC, U01 AG032984 and RC2 AG036528; National Alzheimer's Coordinating Center, U01 AG016976; National Cell Repository for Alzheimer's Disease, U24 AG021886; NIA Late-Onset Alzheimer's Disease Study, U24 AG026395 and U24 AG026390; Banner Sun Health Research Institute, P30 AG019610; Boston University, P30 AG013846, U01 AG10483, R01 CA129769, R01 MH080295, R01 AG017173, R01 AG025259, and R01 AG33193; Columbia University, P50 AG008702 and R37 AG015473; Duke University, P30 AG028377, R01 AG05128, R01 NS39764, and R01 MH60451; Emory University, AG025688; Group Health Research Institute, UO1 AG06781 and UO1 HG004610; Indiana University, P30 AG10133; Johns Hopkins University, P50 AG005146 and R01 AG020688; Massachusetts General Hospital, P50 AG005134; Mayo Clinic, P50 AG016574; Mount Sinai School of Medicine, P50 AG005138 and P01 AG002219; New York University, P30 AG08051, MO1 RR00096, and UL1 RR029893; Northwestern University, P30 AG013854; Oregon Health & Science University, P30 AG008017 and R01 AG026916; Rush University, P30 AG010161, R01 AG019085, R01 AG15819, R01 AG17917, and R01 AG30146; Translational Genomics Research Institute, R01 NS059873 and R01 AG034504; University of Alabama at Birmingham, P50 AG016582 and UL1 RR02777; University of Arizona, R01 AG031581; University of California, Davis, P30 AG010129; University of California, Irvine, P50 AG016573, P50 AG016575, P50 AG016576, and P50 AG016577; University of California, Los Angeles, P50 AG016570; University of California, San Diego, P50 AG005131; University of California, San Francisco, P50 AG023501 and P01 AG019724; University of Kentucky, P30 AG028383 and AG05144; University of Michigan, P50 AG008671; University of Pennsylvania, P30 AG010124; University of Pittsburgh, P50 AG005133 and AG030653; University of Southern California, P50 AG005142; University of Texas Southwestern, P30 AG012300; University of Miami, R01 AG027944, AG010491, AG027944, AG021547, and AG019757; University of Washington, P50 AG005136; Vanderbilt University, R01 AG019085; and Washington University, P50 AG005681 and P01 AG03991. Samples from the National Cell Repository for Alzheimer's Disease, which receives government support under cooperative agreement grant U24 AG21886 awarded by the NIA, were used in this study. The Translational Genomics Research Institute series was also funded by the Banner Alzheimer's Foundation, the Johnnie B. Byrd Sr Alzheimer's Center & Research Institute, the Medical Research Council, and the state of Arizona and also includes samples from the following sites: Newcastle Brain Tissue Resource (funding via the Medical Research Council, local National Health Service trusts, and Newcastle University), MRC London Brain Bank for Neurodegenerative Diseases (funding via the Medical Research Council), South West Dementia Brain Bank (funding via numerous sources including the Higher Education Funding Council for England, Alzheimer's Research Trust, and BRACE as well as North Bristol NHS Trust Research and Innovation Department and DeNDRoN), the Netherlands Brain Bank (funding via numerous sources including Stichting MS Research, BrainNet Europe, Hersenstichting Nederland Breinbrekend Werk, International Parkinson Fonds, and Internationale Stiching Alzheimer Onderzoek), Institut de Neuropatologia, Servei Anatomia Patologica, and Universitat de Barcelona.; Funding for ADNI is through the Northern California Institute for Research and Education by grants from the Alzheimer's Association, Alzheimer's Drug Discovery Foundation, the Dana Foundation, and the National Institute of Biomedical Imaging and Bioengineering and NIA grants U01 AG024904, RC2 AG036535, and K01 AG030514. Support was also from Alzheimer's Association grants IIRG-08-89720 (Dr Farrer) and IIRG-05-14147 (Dr Pericak-Vance) and the US Department of Veterans Affairs Administration, Office of Research and Development, Biomedical Laboratory Research Program. Dr St George-Hyslop is supported by Wellcome Trust, Howard Hughes Medical Institute, and the Canadian Institute of Health Research. NR 37 TC 30 Z9 30 U1 0 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD OCT PY 2012 VL 69 IS 10 BP 1270 EP 1279 DI 10.1001/archneurol.2012.2052 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 016TC UT WOS:000309541400005 PM 22869155 ER PT J AU Gao, X Simon, KC Schwarzschild, MA Ascherio, A AF Gao, Xiang Simon, Kelly C. Schwarzschild, Michael A. Ascherio, Alberto TI Age, Statin Use, and the Risk for Incident Parkinson Disease reply SO ARCHIVES OF NEUROLOGY LA English DT Letter C1 [Gao, Xiang; Ascherio, Alberto] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. [Gao, Xiang; Ascherio, Alberto] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Gao, Xiang; Simon, Kelly C.; Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Ascherio, Alberto] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Schwarzschild, Michael A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Gao, X (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM xiang.gao@channing.harvard.edu NR 6 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD OCT PY 2012 VL 69 IS 10 BP 1381 EP 1381 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 016TC UT WOS:000309541400025 PM 23754004 ER PT J AU Stone, JH Khosroshahi, A Deshpande, V Chan, JKC Heathcote, JG Aalberse, R Azumi, A Bloch, DB Brugge, WR Carruthers, MN Cheuk, W Cornell, L Fernandez-Del Castillo, C Ferry, JA Forcione, D Kloppel, G Hamilos, DL Kamisawa, T Kasashima, S Kawa, S Kawano, M Masaki, Y Notohara, K Okazaki, K Ryu, JK Saeki, T Sahani, D Sato, Y Smyrk, T Stone, JR Takahira, M Umehara, H Webster, G Yamamoto, M Yi, E Yoshino, T Zamboni, G Zen, Y Chari, S AF Stone, John H. Khosroshahi, Arezou Deshpande, Vikram Chan, John K. C. Heathcote, J. Godfrey Aalberse, Rob Azumi, Atsushi Bloch, Donald B. Brugge, William R. Carruthers, Mollie N. Cheuk, Wah Cornell, Lynn Fernandez-Del Castillo, Carlos Ferry, Judith A. Forcione, David Kloeppel, Guenter Hamilos, Daniel L. Kamisawa, Terumi Kasashima, Satomi Kawa, Shigeyuki Kawano, Mitsuhiro Masaki, Yasufumi Notohara, Kenji Okazaki, Kazuichi Ryu, Ji Kon Saeki, Takako Sahani, Dushyant Sato, Yasuharu Smyrk, Thomas Stone, James R. Takahira, Masayuki Umehara, Hisanori Webster, George Yamamoto, Motohisa Yi, Eunhee Yoshino, Tadashi Zamboni, Giuseppe Zen, Yoh Chari, Suresh TI Recommendations for the nomenclature of IgG4-related disease and its individual organ system manifestations SO ARTHRITIS AND RHEUMATISM LA English DT Article ID IMMUNOGLOBULIN G4-ASSOCIATED CHOLANGITIS; AUTOIMMUNE PANCREATITIS; SCLEROSING DISEASE; SERUM IGG4; CLINICOPATHOLOGICAL CHARACTERISTICS; TUBULOINTERSTITIAL NEPHRITIS; LYMPHOPLASMACYTIC AORTITIS; RETROPERITONEAL FIBROSIS; FEATURES; INFILTRATION C1 [Stone, John H.] Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. [Chan, John K. C.; Cheuk, Wah] Queen Elizabeth Hosp, Hong Kong, Hong Kong, Peoples R China. [Heathcote, J. Godfrey] Dalhousie Univ, Halifax, NS, Canada. [Aalberse, Rob] Univ Amsterdam, Amsterdam, Netherlands. [Azumi, Atsushi] Kobe Univ, Grad Sch Med, Kobe, Hyogo 657, Japan. [Azumi, Atsushi] Kobe Kaisei Hosp, Kobe, Hyogo, Japan. [Cornell, Lynn; Smyrk, Thomas; Yi, Eunhee; Chari, Suresh] Mayo Clin Fdn, Rochester, MN USA. [Kloeppel, Guenter] Tech Univ Munich, Munich, Germany. [Kamisawa, Terumi] Tokyo Metropolitan Komagome Hosp, Tokyo, Japan. [Kasashima, Satomi] Kanazawa Med Ctr, Kanazawa, Ishikawa, Japan. [Kawa, Shigeyuki] Shinshu Univ, Matsumoto, Nagano 390, Japan. [Kawano, Mitsuhiro; Takahira, Masayuki] Kanazawa Univ, Grad Sch Med Sci, Kanazawa, Ishikawa, Japan. [Masaki, Yasufumi; Umehara, Hisanori] Kanazawa Med Univ, Uchinada, Ishikawa 92002, Japan. [Notohara, Kenji] Kurashiki Cent Hosp, Kurashiki, Okayama, Japan. [Okazaki, Kazuichi] Kansai Med Univ, Hirakata, Osaka, Japan. [Ryu, Ji Kon] Seoul Natl Univ, Coll Med, Seoul, South Korea. [Saeki, Takako] Nagaoka Red Cross Hosp, Nagaoka, Niigata, Japan. [Sato, Yasuharu; Yoshino, Tadashi] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Okayama, Japan. [Webster, George] UCL, London, England. [Webster, George] Univ Coll London Hosp, London, England. [Yamamoto, Motohisa] Sapporo Med Univ, Sch Med, Sapporo, Hokkaido, Japan. [Zamboni, Giuseppe] Univ Verona, I-37100 Verona, Italy. [Zen, Yoh] Kings Coll London, London WC2R 2LS, England. [Zen, Yoh] Kings Coll Hosp London, London, England. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, 55 Fruit St,Yawkey 2, Boston, MA 02114 USA. EM jhstone@partners.org RI Ryu, Ji Kon/J-5462-2012; Giuseppe, Zamboni/A-5991-2016; OI Giuseppe, Zamboni/0000-0001-7428-4673; Kloppel, Gunter/0000-0002-6688-086X FU NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases) [R13-AR-061254]; Genentech; Biogen Idec; Genzyme; RedPath FX The International Symposium on IgG4-Related Disease was funded by the NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases grant R13-AR-061254) and by grants from Genentech, Biogen Idec, and Genzyme.; Dr. J. H. Stone has received consulting fees from Genentech and Biogen Idec (less than $10,000 each). Dr. Brugge has received consulting fees, speaking fees, and/or honoraria from RedPath (less than $10,000). NR 46 TC 202 Z9 222 U1 4 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 BP 3061 EP 3067 DI 10.1002/art.34593 PG 7 WC Rheumatology SC Rheumatology GA 014VE UT WOS:000309403000001 PM 22736240 ER PT J AU Chung, SA Xie, G Roshandel, D Sherva, R Edberg, JC Kravitz, M Dellaripa, PF Hoffman, GS Mahr, AD Seo, P Specks, U Spiera, RF St Clair, EW Stone, JH Plenge, RM Siminovitch, KA Merkel, PA Monach, PA AF Chung, Sharon A. Xie, Gang Roshandel, Delnaz Sherva, Richard Edberg, Jeffrey C. Kravitz, Megan Dellaripa, Paul F. Hoffman, Gary S. Mahr, Alfred D. Seo, Philip Specks, Ulrich Spiera, Robert F. St Clair, E. William Stone, John H. Plenge, Robert M. Siminovitch, Katherine A. Merkel, Peter A. Monach, Paul A. TI Meta-analysis of genetic polymorphisms in granulomatosis with polyangiitis (Wegener's) reveals shared susceptibility loci with rheumatoid arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID GENOME-WIDE ASSOCIATION; SYSTEMIC-LUPUS-ERYTHEMATOSUS; SINGLE-NUCLEOTIDE POLYMORPHISMS; TYPE-1 DIABETES RISK; ULCERATIVE-COLITIS; AUTOIMMUNE-DISEASES; CROHNS-DISEASE; MULTIPLE-SCLEROSIS; COMMON VARIANTS; REPLICATION AB Objective To examine the association of previously identified autoimmune disease susceptibility loci with granulomatosis with polyangiitis (Wegener's) (GPA), and to determine whether the genetic susceptibility profiles of other autoimmune diseases are associated with those of GPA. Methods Genetic data from 2 cohorts were meta-analyzed. Genotypes for 168 previously identified single-nucleotide polymorphisms (SNPs) associated with susceptibility to different autoimmune diseases were ascertained in a total of 880 patients with GPA and 1,969 control subjects of European descent. Single-marker associations were identified using additive logistic regression models. Associations of multiple SNPs with GPA were assessed using genetic risk scores based on susceptibility loci for Crohn's disease, type 1 diabetes, systemic lupus erythematosus, rheumatoid arthritis (RA), celiac disease, and ulcerative colitis. Adjustment for population substructure was performed in all analyses, using ancestry-informative markers and principal components analysis. Results Genetic polymorphisms in CTLA4 were significantly associated with GPA in the single-marker meta-analysis (odds ratio [OR] 0.79, 95% confidence interval [95% CI] 0.700.89, P = 9.8 x 10-5). The genetic risk score for RA susceptibility markers was significantly associated with GPA (OR 1.05 per 1-unit increase in genetic risk score, 95% CI 1.021.08, P = 5.1 x 10-5). Conclusion RA and GPA may arise from a similar genetic predisposition. Aside from CTLA4, other loci previously found to be associated with common autoimmune diseases were not statistically significantly associated with GPA in this study. C1 [Sherva, Richard; Kravitz, Megan; Mahr, Alfred D.; Merkel, Peter A.; Monach, Paul A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Xie, Gang; Roshandel, Delnaz; Siminovitch, Katherine A.] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Chung, Sharon A.] Univ San Francisco, San Francisco, CA 94117 USA. [Edberg, Jeffrey C.] Univ Alabama Birmingham, Birmingham, AL USA. [Dellaripa, Paul F.; Plenge, Robert M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hoffman, Gary S.] Cleveland Clin, Cleveland, OH 44106 USA. [Mahr, Alfred D.] Univ Paris 07, Paris, France. [Mahr, Alfred D.] Hop St Louis, AP HP, Paris, France. [Seo, Philip] Johns Hopkins Univ, Baltimore, MD USA. [Specks, Ulrich] Mayo Clin, Coll Med, Rochester, MN USA. [Spiera, Robert F.] Hosp Special Surg, New York, NY 10021 USA. [St Clair, E. William] Duke Univ, Durham, NC USA. [Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Monach, PA (reprint author), Boston Univ, Sch Med, 72 E Concord St,E-533, Boston, MA 02118 USA. EM pmonach@bu.edu RI Siminovitch, Katherine/K-1475-2013 FU Rosalind Russell Medical Research Center for Arthritis; NIH [5 KL2-RR-024130, R01-AR-047799, U54-RR-019497]; Vasculitis Foundation (US); Ontario Research Fund [RE01-061]; Societe Nationale Francaise de Medecine Interne; Arthritis Foundation; NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases [K24-AR-02224]; Vasculitis Foundation (Canada) FX Supported by the Rosalind Russell Medical Research Center for Arthritis (grant to Dr. Chung), the NIH (grant 5 KL2-RR-024130 to Dr. Chung, grant R01-AR-047799 to Drs. Edberg and Merkel, grant U54-RR-019497 to Dr. Merkel with fellowship support to Dr. Mahr), the Vasculitis Foundation (US and Canada, grant to Dr. Siminovitch), the Ontario Research Fund (grant RE01-061 to Dr. Siminovitch), the Societe Nationale Francaise de Medecine Interne (grant to Dr. Mahr), and the Arthritis Foundation (Arthritis Investigator Award to Dr. Monach). Dr. Siminovitch holds a Canada Research Chair in the Mechanisms Regulating Immunologic Disease at the University of Toronto and the Sherman Family Chair in Genomic Medicine at Mount Sinai Hospital. Dr. Merkel is recipient of an NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases Mid-Career Development Award in Clinical Investigation (grant K24-AR-02224). NR 69 TC 12 Z9 12 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2012 VL 64 IS 10 BP 3463 EP 3471 DI 10.1002/art.34496 PG 9 WC Rheumatology SC Rheumatology GA 014VE UT WOS:000309403000044 PM 22508400 ER PT J AU Thornton, E Howard, SA Jagannathan, J Krajewski, KM Shinagare, AB O'Regan, K Cleary, JM Ramaiya, NH AF Thornton, E. Howard, S. A. Jagannathan, J. Krajewski, K. M. Shinagare, A. B. O'Regan, K. Cleary, J. M. Ramaiya, N. H. TI Imaging features of bowel toxicities in the setting of molecular targeted therapies in cancer patients SO BRITISH JOURNAL OF RADIOLOGY LA English DT Review ID BEVACIZUMAB; PERFORATION; ERLOTINIB; TRIAL AB Molecular targeted therapies are becoming ubiquitous in cancer treatment. These drugs may cause gastrointestinal toxicities including perforation, pneumatosis, enteritis, colitis and fistula formation. Knowledge of these complications and their management enables early radiological identification and appropriate intervention, reducing patient morbidity and mortality. C1 [Thornton, E.; Howard, S. A.; Jagannathan, J.; Krajewski, K. M.; Shinagare, A. B.; O'Regan, K.; Cleary, J. M.; Ramaiya, N. H.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. RP Shinagare, AB (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM ashinagare@partners.org NR 13 TC 9 Z9 9 U1 0 U2 0 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PD OCT PY 2012 VL 85 IS 1018 BP 1420 EP 1426 DI 10.1259/bjr/19815818 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 018OE UT WOS:000309669800036 PM 22674709 ER PT J AU Yang, M Sun, T Zhou, YF Wang, L Liu, L Zhang, XJ Tang, XH Zhou, M Kuang, PQ Tan, W Li, H Yuan, QP Yu, DK AF Yang, Ming Sun, Tong Zhou, Yifeng Wang, Li Liu, Li Zhang, Xiaojiao Tang, Xiaohu Zhou, Mo Kuang, Pengqun Tan, Wen Li, Hui Yuan, Qipeng Yu, Dianke TI The functional cytotoxic T lymphocyte-associated Protein 4 49G-to-A genetic variant and risk of pancreatic cancer SO CANCER LA English DT Article DE pancreatic cancer; CTLA-4; single-nucleotide polymorphism; susceptibility; association study ID CTLA-4 BLOCKADE; PROSTATE-CANCER; IMMUNE-SYSTEM; CYTOTOXIC-T-LYMPHOCYTE-ANTIGEN-4; IMMUNOTHERAPY; POLYMORPHISMS; CD28; POPULATION; DEATH AB BACKGROUND: Antitumor T lymphocytes play an essential part in immune surveillance of cancer cells. Cytotoxic T lymphocyteassociated Protein 4 (CTLA-4) is a negative regulator of T cell activation and proliferation and therefore influences immune surveillance of carcinogenesis of pancreas. Thus, this study examined the association between functional CTLA-4 49G-to-A (49G>A) single-nucleotide polymorphism and pancreatic cancer risk. METHODS: Genotypes were determined in 368 patients with pancreatic cancer and 926 controls, and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. RESULTS: A significant increased risk of pancreatic cancer was found to be associated with the CTLA-4 49G>A single-nucleotide polymorphism. Compared with noncarriers, the OR of developing pancreatic cancer for CTLA-4 49 GA or AA carriers was 1.75 (95% CI = 1.34-2.30, P = 4.83 X 10-5) or 2.54 (95% CI = 1.67-3.87, P = 1.36 X 10-5), respectively. In stratified analyses, the association was more pronounced in GA and AA carriers aged =60 years (OR = 3.10, 95% CI = 2.15-4.47, Pinteraction = .002), smokers with GA and AA genotypes (OR = 3.92, 95% CI = 2.39-6.43, Pinteraction = .037), and drinkers with GA and AA genotypes (OR = 4.55, 95% CI = 2.65-7.82, Pinteraction = .042), compared with GG carriers. Moreover, a supermultiplicative interaction between the CTLA-4 49AA genotype and smoking plus drinking was also evident in intensifying risk of pancreatic cancer (Pinteraction = 5.64 X 10-12). CONCLUSIONS: These results suggest that CTLA-4 49G>A polymorphism is involved in susceptibility to developing pancreatic cancer, alone and in a geneenvironment interaction manner. Cancer 2012. (c) 2012 American Cancer Society. C1 [Yang, Ming; Liu, Li; Zhang, Xiaojiao; Tang, Xiaohu; Zhou, Mo; Kuang, Pengqun; Yuan, Qipeng] Beijing Univ Chem Technol, Coll Life Sci & Technol, Beijing 100029, Peoples R China. [Tan, Wen; Yu, Dianke] Chinese Acad Med Sci, Dept Etiol & Carcinogenesis, Canc Inst & Hosp, Beijing 100730, Peoples R China. [Wang, Li; Tan, Wen; Li, Hui; Yu, Dianke] Peking Union Med Coll, Beijing 100021, Peoples R China. [Wang, Li; Li, Hui] Chinese Acad Med Sci, Inst Basic Med Sci, Dept Epidemiol, Beijing 100730, Peoples R China. [Sun, Tong] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sun, Tong] Harvard Univ, Sch Med, Boston, MA USA. [Zhou, Yifeng] Soochow Univ, Lab Canc Mol Genet, Sch Basic Med & Biol Sci, Coll Med, Suzhou, Peoples R China. RP Yang, M (reprint author), Beijing Univ Chem Technol, Coll Life Sci & Technol, POB 53, Beijing 100029, Peoples R China. EM yangm@mail.buct.edu.cn; yudianking@163.com RI Yang, Ming/G-4705-2012 OI Yang, Ming/0000-0002-7722-7487 FU Beijing Nova Program [2010B013]; Fundamental Research Funds for the Central Universities [ZZ1234]; National Natural Science Foundation of China [81000872]; PhD Programs Foundation of Chinese Ministry of Education [20101106120011] FX Supported by the Beijing Nova Program (grant 2010B013 to M. Yang), the Fundamental Research Funds for the Central Universities (grant ZZ1234 to M. Yang), National Natural Science Foundation of China (grant 81000872 to D. Yu), and the PhD Programs Foundation of the Chinese Ministry of Education (grant 20101106120011 to D. Yu). NR 30 TC 20 Z9 21 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD OCT 1 PY 2012 VL 118 IS 19 BP 4681 EP 4686 DI 10.1002/cncr.27455 PG 6 WC Oncology SC Oncology GA 008BK UT WOS:000308931900008 PM 22359319 ER PT J AU Ross, RW Galsky, MD Febbo, P Barry, M Richie, JP Xie, WL Fennessy, FM Bhatt, RS Hayes, J Choueiri, TK Tempany, CM Kantoff, PW Taplin, ME Oh, WK AF Ross, Robert W. Galsky, Matthew D. Febbo, Phil Barry, Marc Richie, Jerome P. Xie, Wanling Fennessy, Fiona M. Bhatt, Rupal S. Hayes, Julia Choueiri, Toni K. Tempany, Clare M. Kantoff, Philip W. Taplin, Mary E. Oh, William K. TI Phase 2 study of neoadjuvant docetaxel plus bevacizumab in patients with high-risk localized prostate cancer SO CANCER LA English DT Article DE prostate cancer; neoadjuvant; docetaxel; bevacizumab; high-risk localized ID COMPARING RADICAL PROSTATECTOMY; LEUKEMIA GROUP-B; ANDROGEN BLOCKADE; II TRIAL; MITOXANTRONE; PREDNISONE; ESTRAMUSTINE; THERAPY; THALIDOMIDE; DISEASE AB BACKGROUND: Treatment of high-risk localized prostate cancer remains inadequate. The authors performed a phase 2 multicenter trial of neoadjuvant docetaxel plus bevacizumab before radical prostatectomy. METHODS: Eligibility included any of the following: prostate-specific antigen (PSA) >20 ng/mL or PSA velocity >2 ng/mL/y, cT3 disease, any biopsy Gleason score 8 to 10, and Gleason score 7 with T3 disease by endorectal magnetic resonance imaging (MRI) at 1.5 T. Also, those with =50% biopsy cores involved and either Gleason score 7, PSA >10, or cT2 disease were eligible. Patients were treated with docetaxel 70 mg/m2 every 3 weeks for 6 cycles and bevacizumab 15 mg/m2 every 3 weeks for 5 cycles. The primary endpoint was partial response by endorectal MRI. RESULTS: Forty-one patients were treated. Median age was 55 years (range, 40-66 years). Baseline characteristics included: median PSA, 10.1 ng/mL; cT2, 49%, cT3, 32%; and Gleason score 8 to 10, 73%. Thirty-eight of 41 (93%) patients completed all 6 cycles. Grade =3 adverse events were rare, although 3 of 41 (7%) experienced febrile neutropenia. Twelve patients (29%; 95% confidence interval [CI], 16%-45%) achieved a >50% reduction in tumor volume, and 9 patients (22%; 95% CI, 11%-38%) achieved a >50% post-treatment decline in PSA. Thirty-seven of the 41 patients underwent radical prostatectomy; there were no complete pathologic responses. CONCLUSIONS: Neoadjuvant docetaxel and bevacizumab is safe, and results in reductions in both tumor volume and serum PSA, in men with high-risk localized prostate cancer. The role of neoadjuvant chemotherapy in prostate cancer, and perioperative antiangiogenic therapy in general, requires further elucidation through ongoing and planned trials. Cancer 2012. (c) 2012 American Cancer Society. C1 [Galsky, Matthew D.] Mt Sinai Sch Med, Dept Med, Div Hematol Oncol, Tisch Canc Inst, New York, NY 10029 USA. [Ross, Robert W.; Xie, Wanling; Fennessy, Fiona M.; Choueiri, Toni K.; Tempany, Clare M.; Kantoff, Philip W.; Taplin, Mary E.; Oh, William K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Febbo, Phil] Duke Univ, Med Ctr, Dept Med, Div Hematol Oncol, Raleigh, NC USA. [Barry, Marc] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA. [Richie, Jerome P.] Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. [Bhatt, Rupal S.] Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Boston, MA 02215 USA. RP Oh, WK (reprint author), Mt Sinai Sch Med, Dept Med, Div Hematol Oncol, Tisch Canc Inst, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM william.oh@mssm.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 FU Genentech; Sanofi-Aventis FX Supported by Genentech and Sanofi-Aventis. NR 31 TC 27 Z9 28 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD OCT 1 PY 2012 VL 118 IS 19 BP 4777 EP 4784 DI 10.1002/cncr.27416 PG 8 WC Oncology SC Oncology GA 008BK UT WOS:000308931900018 PM 22282219 ER PT J AU Katz, ML Archer, LE Peppercorn, JM Kereakoglow, S Collyar, DE Burstein, HJ Schilsky, RL Partridge, AH AF Katz, Mira L. Archer, Laura E. Peppercorn, Jeffrey M. Kereakoglow, Sandra Collyar, Deborah E. Burstein, Harold J. Schilsky, Richard L. Partridge, Ann H. TI Patient advocates' role in clinical trials SO CANCER LA English DT Article DE cancer; clinical trials; patient advocate; cooperative groups; communication ID PARTNERSHIP AB BACKGROUND: Patient advocates are increasingly involved in cooperative group trials, single-institution cancer programs, and peer-review of research applications. The purpose of this study was to evaluate the role and value of patient advocates from the perspective of Cancer and Leukemia Group B (CALGB) advocates and investigators. METHODS: An online survey was sent to current and past (within 5 years) patient advocates and investigators. RESULTS. Response rates were 72.7% (16 of 22) for advocates and 56.4% (102 of 181) for investigators. Patient advocates were more likely than investigators to report the following: the clinical trial process benefited from advocate involvement on committees (100% of advocates vs 72.1% of investigators; P < .05), advocates contribute to protocol development (92.8% vs 33.8%, respectively; P < .001), the cultural appropriateness of protocols (21.4% vs 10.4%, respectively; P < .05), advocates assist with patient accrual (78.6% vs 23.4%, respectively; P < .001), and advocates add value to concept development and protocol review (100% vs 63.2%, respectively; P < .001). Over half of advocates and investigators reported gaps in patient advocate knowledge and suggested that additional clinical trials training was needed. To improve clinical trials, advocates suggested their earlier involvement in protocol development and increased support from investigators. CALGB investigators recommended improving patient advocate selection and communication skills training: CONCLUSIONS: The majority of patient advocates and investigators perceived benefits from advocate involvement in the clinical trials process; patient advocates placed more value on their role than investigators. The current results indicated that strategies to improve advocacy training and advocate-investigator communication may further enhance the role of patient advocates, and future studies that clarify the role of advocates in the prioritization and development of protocol, consent, and education materials, and on patient accrual, are warranted. Cancer 2012. (c) 2012 American Cancer Society. C1 [Katz, Mira L.] Ohio State Univ, Coll Publ Hlth, Div Hlth Behav & Hlth Promot, Columbus, OH 43201 USA. [Archer, Laura E.] Duke Univ, Med Ctr, Canc & Leukemia Grp B, Ctr Stat, Durham, NC USA. [Peppercorn, Jeffrey M.] Duke Univ, Med Ctr, Div Med Oncol, Durham, NC USA. [Kereakoglow, Sandra] Dana Farber Canc Inst, Div Womens Canc, Boston, MA 02115 USA. [Collyar, Deborah E.] Patient Advocates Res, Danville, CA USA. [Burstein, Harold J.; Partridge, Ann H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Schilsky, Richard L.] Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA. RP Katz, ML (reprint author), Ohio State Univ, Coll Publ Hlth, Div Hlth Behav & Hlth Promot, Suite 525,1590 N High St, Columbus, OH 43201 USA. EM mira.katz@osumc.edu RI Katz, Mira/B-6957-2012 NR 11 TC 5 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD OCT 1 PY 2012 VL 118 IS 19 BP 4801 EP 4805 DI 10.1002/cncr.27485 PG 5 WC Oncology SC Oncology GA 008BK UT WOS:000308931900021 PM 22392584 ER PT J AU Viswanath, K Nagler, RH Bigman-Galimore, CA McCauley, MP Jung, M Ramanadhan, S AF Viswanath, K. Nagler, Rebekah H. Bigman-Galimore, Cabral A. McCauley, Michael P. Jung, Minsoo Ramanadhan, Shoba TI The Communications Revolution and Health Inequalities in the 21st Century: Implications for Cancer Control SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SERVICES TASK-FORCE; INFORMATION-SEEKING; PERCEIVED AMBIGUITY; PREVENTION RECOMMENDATIONS; UNITED-STATES; RISK; PERCEPTIONS; BREAST; PROSTATE; SOCIETY AB The radical and transformative developments in information and communication technologies (ICT) offer unprecedented opportunities to promote cancer control and enhance population and individual health. However, the current context in which these technologies are being deployed-where cancer incidence and mortality and communication are characterized by inequalities among different racial/ethnic and socioeconomic status groups-raises important questions for cancer communication research, policy, and practice. Drawing on illustrative data, this essay characterizes the communications revolution and elucidates its implications for cancer control, with a particular focus on communication inequalities and cancer disparities. Cancer Epidemiol Biomarkers Prev; 21(10); 1701-8. (c) 2012 AACR. C1 [Viswanath, K.; Nagler, Rebekah H.; Bigman-Galimore, Cabral A.; McCauley, Michael P.] Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Viswanath, K.; Nagler, Rebekah H.; Bigman-Galimore, Cabral A.; McCauley, Michael P.; Jung, Minsoo; Ramanadhan, Shoba] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Viswanath, K (reprint author), Harvard Univ, Sch Publ Hlth, 450 Brookline Ave LW601, Boston, MA 02215 USA. EM vish_viswanath@dfci.harvard.edu RI McCauley, Michael/C-3642-2014; OI McCauley, Michael/0000-0003-3851-1765; Jung, Minsoo/0000-0003-3317-6507 FU NIH [R01 CA122894, R01CA132651-05, R25 CA057713] FX This work was supported by grants from the NIH: R01 CA122894, R01CA132651-05, and R25 CA057713. NR 66 TC 36 Z9 38 U1 1 U2 13 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2012 VL 21 IS 10 BP 1701 EP 1708 DI 10.1158/1055-9965.EPI-12-0852 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 017FS UT WOS:000309576100012 PM 23045545 ER PT J AU Warren, H Dudbridge, F Fletcher, O Orr, N Johnson, N Hopper, JL Apicella, C Southey, MC Mahmoodi, M Schmidt, MK Broeks, A Cornelissen, S Braaf, LM Muir, KR Lophatananon, A Chaiwerawattana, A Wiangnon, S Fasching, PA Beckmann, MW Ekici, AB Schulz-Wendtland, R Sawyer, EJ Tomlinson, I Kerin, M Burwinkel, B Marme, F Schneeweiss, A Sohn, C Guenel, P Truong, T Laurent-Puig, P Mulot, C Bojesen, SE Nielsen, SF Flyger, H Nordestgaard, BG Milne, RL Benitez, J Arias-Perez, JI Zamora, MP Anton-Culver, H Ziogas, A Bernstein, L Dur, CC Brenner, H Muller, H Arndt, V Langheinz, A Meindl, A Golatta, M Bartram, CR Schmutzler, RK Brauch, H Justenhoven, C Bruning, T Chang-Claude, J Wang-Gohrke, S Eilber, U Dork, T Schurmann, P Bremer, M Hillemanns, P Nevanlinna, H Muranen, TA Aittomaki, K Blomqvist, C Bogdanova, N Antonenkova, N Rogov, Y Bermisheva, M Prokofyeva, D Zinnatullina, G Khusnutdinova, E Lindblom, A Margolin, S Mannermaa, A Kosma, VM Hartikainen, JM Kataja, V Chenevix-Trench, G Beesley, J Chen, XQ Lambrechts, D Smeets, A Paridaens, R Weltens, C Flesch-Janys, D Buck, K Behrens, S Peterlongo, P Bernard, L Manoukian, S Radice, P Couch, FJ Vachon, C Wang, XS Olson, J Giles, G Baglietto, L McLean, CA Severi, G John, EM Miron, A Winqvist, R Pylkas, K Jukkola-Vuorinen, A Grip, M Andrulis, IL Knight, JA Mulligan, AM Weerasooriya, N Devilee, P Tollenaar, RAEM Martens, JWM Seynaeve, CM Hooning, MJ Hollestelle, A Jager, A Tilanus-Linthorst, MMA Hall, P Czene, K Liu, JJ Li, JM Cox, A Cross, SS Brock, IW Reed, MWR Pharoah, P Blows, FM Dunning, AM Ghous-saini, M Ashworth, A Swerdlow, A Jones, M Schoemaker, M Easton, DF Humphreys, M Wang, Q Peto, J dos-Santos-Silva, I AF Warren, Helen Dudbridge, Frank Fletcher, Olivia Orr, Nick Johnson, Nichola Hopper, John L. Apicella, Carmel Southey, Melissa C. Mahmoodi, Maryam Schmidt, Marjanka K. Broeks, Annegien Cornelissen, Sten Braaf, Linda M. Muir, Kenneth R. Lophatananon, Artitaya Chaiwerawattana, Arkom Wiangnon, Surapon Fasching, Peter A. Beckmann, Matthias W. Ekici, Arif B. Schulz-Wendtland, Ruediger Sawyer, Elinor J. Tomlinson, Ian Kerin, Michael Burwinkel, Barbara Marme, Frederik Schneeweiss, Andreas Sohn, Christof Guenel, Pascal Therese Truong Laurent-Puig, Pierre Mulot, Claire Bojesen, Stig E. Nielsen, Sune F. Flyger, Henrik Nordestgaard, Borge G. Milne, Roger L. Benitez, Javier Arias-Perez, Jose-Ignacio Pilar Zamora, M. Anton-Culver, Hoda Ziogas, Argyrios Bernstein, Leslie Dur, Christina Clarke Brenner, Hermann Mueller, Heiko Arndt, Volker Langheinz, Anne Meindl, Alfons Golatta, Michael Bartram, Claus R. Schmutzler, Rita K. Brauch, Hiltrud Justenhoven, Christina Bruening, Thomas Chang-Claude, Jenny Wang-Gohrke, Shan Eilber, Ursula Doerk, Thilo Schuermann, Peter Bremer, Michael Hillemanns, Peter Nevanlinna, Heli Muranen, Taru A. Aittomaki, Kristiina Blomqvist, Carl Bogdanova, Natalia Antonenkova, Natalia Rogov, Yuriy Bermisheva, Marina Prokofyeva, Darya Zinnatullina, Guzel Khusnutdinova, Elza Lindblom, Annika Margolin, Sara Mannermaa, Arto Kosma, Veli-Matti Hartikainen, Jaana M. Kataja, Vesa Chenevix-Trench, Georgia Beesley, Jonathan Chen, Xiaoqing Lambrechts, Diether Smeets, Ann Paridaens, Robert Weltens, Caroline Flesch-Janys, Dieter Buck, Katharina Behrens, Sabine Peterlongo, Paolo Bernard, Loris Manoukian, Siranoush Radice, Paolo Couch, Fergus J. Vachon, Celine Wang, Xianshu Olson, Janet Giles, Graham Baglietto, Laura McLean, Cariona A. Severi, Gianluca John, Esther M. Miron, Alexander Winqvist, Robert Pylkas, Katri Jukkola-Vuorinen, Arja Grip, Mervi Andrulis, Irene L. Knight, Julia A. Mulligan, Anna Marie Weerasooriya, Nayana Devilee, Peter Tollenaar, Robert A. E. M. Martens, John W. M. Seynaeve, Caroline M. Hooning, Maartje J. Hollestelle, Antoinette Jager, Agnes Tilanus-Linthorst, Madeleine M. A. Hall, Per Czene, Kamila Liu, Jianjun Li, Jingmei Cox, Angela Cross, Simon S. Brock, Ian W. Reed, Malcolm W. R. Pharoah, Paul Blows, Fiona M. Dunning, Alison M. Ghous-saini, Maya Ashworth, Alan Swerdlow, Anthony Jones, Michael Schoemaker, Minouk Easton, Douglas F. Humphreys, Manjeet Wang, Qin Peto, Julian dos-Santos-Silva, Isabel CA GENICA Network KConFab Investigators Australian Ovarian Canc Study Grp TI 9q31.2-rs865686 as a Susceptibility Locus for Estrogen Receptor-Positive Breast Cancer: Evidence from the Breast Cancer Association Consortium SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENOME-WIDE ASSOCIATION; CONFER SUSCEPTIBILITY; COMMON VARIANTS; GENETIC RISK; IDENTIFIES 2; POPULATION; MENARCHE; ALLELES; LINKAGE; 5P12 AB Background: Our recent genome-wide association study identified a novel breast cancer susceptibility locus at 9q31.2 (rs865686). Methods: To further investigate the rs865686-breast cancer association, we conducted a replication study within the Breast Cancer Association Consortium, which comprises 37 case-control studies (48,394 cases, 50,836 controls). Results: This replication study provides additional strong evidence of an inverse association between rs865686 and breast cancer risk [study-adjusted per G-allele OR, 0.90; 95% confidence interval (CI), 0.88; 0.91, P = 2.01 x 10(-29)] among women of European ancestry. There were ethnic differences in the estimated minor (G)-allele frequency among controls [0.09, 0.30, and 0.38 among, respectively, Asians, Eastern Europeans, and other Europeans; P for heterogeneity (P-het) -1.3 x 10(-143)], but no evidence of ethnic differences in per allele OR (P-het = 0.43). rs865686 was associated with estrogen receptor-positive (ER+) disease (per G-allele OR, 0.89; 95% CI, 0.86-0.91; P = 3.13 x 10(-22)) but less strongly, if at all, with ER-negative (ER+) disease (OR, 0.98; 95% CI, 0.941.02; P = 0.26; P-het = 1.16 x 10(-6)), with no evidence of independent heterogeneity by progesterone receptor or HER2 status. The strength of the breast cancer association decreased with increasing age at diagnosis, with case-only analysis showing a trend in the number of copies of the Gallele with increasing age at diagnosis (P for linear trend = 0.0095), but only among women with ER+ tumors. Conclusions: This study is the first to show that rs865686 is a susceptibility marker for ER+ breast cancer. Impact: The findings further support the view that genetic susceptibility varies according to tumor subtype. Cancer Epidemiol Biomarkers Prev; 21(10); 1783-91. (c) 2012 AACR. C1 [Warren, Helen; Dudbridge, Frank; Jager, Agnes; Peto, Julian; dos-Santos-Silva, Isabel] Univ London London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, London WC1E 7HT, England. [Fletcher, Olivia; Orr, Nick; Johnson, Nichola; Ashworth, Alan] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. [Sawyer, Elinor J.] Kings Coll London, Guys & St Thomas NHS Fdn Trust, NIHR Comprehens Biomed Res Ctr, Div Canc Studies, London WC2R 2LS, England. [Hopper, John L.; Apicella, Carmel; Giles, Graham; Baglietto, Laura; Severi, Gianluca] Univ Melbourne, Ctr Mol Envi onm Genet & Analyt Epidemiol, Sch Populat Hlth, Melbourne, Vic, Australia. [Southey, Melissa C.; Mahmoodi, Maryam] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia. [KConFab Investigators] Peter MacCallum Canc Ctr, Kathleen Cuningham Consortium Res Familial Breast, Div Res, Melbourne, Vic, Australia. [Giles, Graham; Baglietto, Laura; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [McLean, Cariona A.] Alfred Hosp, Melbourne, Vic, Australia. [Schmidt, Marjanka K.] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands. [Schmidt, Marjanka K.; Broeks, Annegien; Cornelissen, Sten; Braaf, Linda M.] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Mol Pathol, Amsterdam, Netherlands. [Muir, Kenneth R.; Lophatananon, Artitaya] Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England. [Chaiwerawattana, Arkom] Natl Canc Inst Thailand, Minist Publ Hlth, Dept Acad Support, Nonthaburi, Thailand. [Wiangnon, Surapon] Khon Kaen Univ, Sch Med, Dept Pediat, Khon Kaen, Thailand. [Fasching, Peter A.; Beckmann, Matthias W.] Univ Breast Ctr Franconia, Dept Gynecol & Obstet, Brest, France. [Schulz-Wendtland, Ruediger] Univ Hosp Erlangen, Inst Diagnost Radiol, Erlangen, Germany. [Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany. [Tomlinson, Ian] Univ Oxford, Welcome Trust Ctr Human Genet, Oxford, England. [Tomlinson, Ian] Univ Oxford, Oxford Biomed Res Ctr, Oxford, England. [Kerin, Michael] Univ Hosp Galway, Inst Clin Sci, Galway, Ireland. [Burwinkel, Barbara; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Langheinz, Anne; Golatta, Michael] Univ Heidelberg Hosp, Dept Obstet & Gynecol, Heidelberg, Germany. [Marme, Frederik; Schneeweiss, Andreas] Univ Heidelberg, Natl Ctr Tumor Dis, D-6900 Heidelberg, Germany. [Bartram, Claus R.] Univ Heidelberg, Inst Human Genet, D-6900 Heidelberg, Germany. [Guenel, Pascal; Therese Truong] INSERM, CESP Ctr Res Epidemiol & Populat Hlth, U1018, F-75654 Paris 13, France. [Guenel, Pascal; Therese Truong] Univ Paris Sud, UMRS1018, Villejuif, France. [Laurent-Puig, Pierre; Mulot, Claire] Univ Paris 05, INSERM, UMR EPIGENETEC S775, Paris, France. [Bojesen, Stig E.; Nielsen, Sune F.; Nordestgaard, Borge G.] Herlev Hosp, Dept Clin Biochem, Copenhagen Gen Populat Study, Copenhagen, Denmark. [Bojesen, Stig E.; Nielsen, Sune F.; Nordestgaard, Borge G.] Copenhagen Univ Hosp, Herlev Hosp, Fac Hlth Sci, Copenhagen, Denmark. [Flyger, Henrik] Copenhagen Univ Hosp, Herlev Hosp, Dept Breast Surg, Copenhagen, Denmark. [Milne, Roger L.] Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain. [Benitez, Javier] Spanish Natl Canc Res Ctr CNIO, Human Genet Grp, Human Canc Genet Programme, Madrid, Spain. [Arias-Perez, Jose-Ignacio] Hosp Monte Naranco, Serv Cirugia Gen & Especialidades, Oviedo, Spain. [Pilar Zamora, M.] Hosp Univ La Paz, Med Oncol Serv, Madrid, Spain. [Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Dur, Christina Clarke; John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA. [Meindl, Alfons] Tech Univ Munich, Div Gynaecol & Obstet, Munich, Germany. [Schmutzler, Rita K.] Univ Hosp Cologne, Ctr Mol Med Cologne CMMC, Dept Obstet & Gynaecol, Div Mol Gynecooncol, Cologne, Germany. [Brauch, Hiltrud; Justenhoven, Christina] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-7000 Stuttgart, Germany. [Brauch, Hiltrud; Justenhoven, Christina] Univ Tubingen, Tubingen, Germany. [Bruening, Thomas] Inst Prevent & Occupat Med German Social Accident, Bochum, Germany. Johanniter Krankenhaus, Evangel Kliniken Bonn gGmbH, Dept Internal Med, Bonn, Germany. Univ Bonn, Inst Pathol, Fac Med, Bonn, Germany. [GENICA Network] Univ Saarland, Fac Med, Med Ctr, Inst & Outpatient Clin Occupat Med, D-6650 Homburg, Germany. [Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynecol, Ulm, Germany. [Bremer, Michael; Bogdanova, Natalia] Hannover Med Sch, Clin Radiat Oncol OE 8240, D-3000 Hannover, Germany. [Hillemanns, Peter] Hannover Med Sch, Clin Obstet & Gynaecol OE 6410, D-3000 Hannover, Germany. [Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.] Biomedicum Helsinki, Dept Obstet & Gynecol, Helsinki, Finland. [Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.] Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland. [Rogov, Yuriy] Belarussian Med Acad Postgrad Educ, Dept Pathol, Minsk, Byelarus. [Bermisheva, Marina; Prokofyeva, Darya; Khusnutdinova, Elza] Russian Acad Sci, Ufa Sci Ctr, Inst Biochem & Genet, Moscow 117901, Russia. [Zinnatullina, Guzel] Oncol Clin Republ Bashkortostan, Ufa, Russia. [Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. [Hall, Per; Czene, Kamila] Karolinska Inst, Dept Med Biostat & Epidemiol, Stockholm, Sweden. [Margolin, Sara] Karolinska Univ Hosp, Dept Oncol & Pathol, Stockholm, Sweden. [Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.] Univ Eastern Finland, Canc Ctr Eastern Finland, Inst Clin Med Pathol & Forens Med, Bioctr Kuopio, Kuopio, Finland. [Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.] Kuopio Univ Hosp, Dept Clin Pathol, Imaging Ctr, Kuopio, Finland. [Kataja, Vesa] Univ Eastern Finland, Ctr Canc, Kuopio Univ Hosp, Inst Clin Med, Kuopio, Finland. [Chenevix-Trench, Georgia; Beesley, Jonathan; Chen, Xiaoqing; Australian Ovarian Canc Study Grp] Royal Brisbane Hosp, Queensland Inst Med Res, Brisbane, Qld 4029, Australia. [Lambrechts, Diether] VIB, Vesalius Res Ctr, Brussels, Belgium. [Smeets, Ann; Paridaens, Robert; Weltens, Caroline] Katholieke Univ Leuven, Hosp Gasthuisberg, Leuven Multidisciplinary Breast Ctr LMBC, Louvain, Belgium. [Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Dept Canc Epidemiol, Clin Canc Registry, Hamburg, Germany. [Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, Hamburg, Germany. [Manoukian, Siranoush] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predict Med, Tumori, Italy. [Bernard, Loris] Consortium Genom Technol Cogentech, Milan, Italy. [Couch, Fergus J.; Wang, Xianshu] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Couch, Fergus J.; Vachon, Celine; Wang, Xianshu; Olson, Janet] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Miron, Alexander] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Jukkola-Vuorinen, Arja] Univ Oulu, Oulu Univ Hosp, Dept Oncol, Oulu, Finland. [Grip, Mervi] Univ Oulu, Oulu Univ Hosp, Dept Surg, Oulu, Finland. [Andrulis, Irene L.; Knight, Julia A.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Taipei, Taiwan. [Andrulis, Irene L.] Univ Toronto, Dalla Lana Sch Publ Hlth, Dept Mol Genet, Toronto, ON M5S 1A1, Canada. [Mulligan, Anna Marie] Univ Toronto, Dalla Lana Sch Publ Hlth, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A1, Canada. [Knight, Julia A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON M5S 1A1, Canada. [Mulligan, Anna Marie] St Michaels Hosp, Li Ka Shing Knowledge Inst, Dept Lab Med, Toronto, ON, Canada. [Mulligan, Anna Marie] St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Toronto, ON, Canada. [Weerasooriya, Nayana] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Devilee, Peter] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands. [Devilee, Peter] Leiden Univ, Med Ctr, Dept Pathol, Leiden, Netherlands. [Tollenaar, Robert A. E. M.] Leiden Univ, Med Ctr, Dept Surg Oncol, Leiden, Netherlands. [Martens, John W. M.; Hollestelle, Antoinette] Erasmus Univ, Med Ctr, Dept Med Oncol, Josephine Nefkens Inst, NL-3000 DR Rotterdam, Netherlands. [Seynaeve, Caroline M.] Erasmus MC, Dr Daniel Den Hoed Canc Ctr, Rotterdam Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands. [Hooning, Maartje J.; Jager, Agnes] Erasmus Univ, Med Ctr, Family Canc Clin, Dept Med Oncol, NL-3000 DR Rotterdam, Netherlands. [Tilanus-Linthorst, Madeleine M. A.] Erasmus Univ, Med Ctr, Family Canc Clin, Dept Surg Oncol, NL-3000 DR Rotterdam, Netherlands. [Liu, Jianjun; Li, Jingmei] Genome Inst Singapore, Singapore, Singapore. [Cox, Angela; Brock, Ian W.; Reed, Malcolm W. R.] Univ Sheffield, Dept Oncol, Sheffield, S Yorkshire, England. [Cross, Simon S.] Univ Sheffield, Dept Neurosci, Sheffield, S Yorkshire, England. [Pharoah, Paul; Blows, Fiona M.; Dunning, Alison M.; Ghous-saini, Maya] Univ Cambridge, Dept Oncol, Cambridge, England. [Humphreys, Manjeet; Wang, Qin] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England. [Swerdlow, Anthony; Jones, Michael; Schoemaker, Minouk] Inst Canc Res, Div Genet & Epidemiol, Sutton, Surrey, England. RP dos-Santos-Silva, I (reprint author), Univ London London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, Keppel St, London WC1E 7HT, England. EM isabel.silva@lshtm.ac.uk RI Bruning, Thomas/G-8120-2015; Khusnutdinova, Elza/A-4810-2013; Brenner, Hermann/B-4627-2017; manoukian, siranoush/E-7132-2017; Verdrengh, Evelien/H-4571-2012; truong, therese/A-2837-2013; Hartikainen, Jaana/E-6256-2015; Li, Jingmei/I-2904-2012; laurent-puig, pierre/B-2226-2013; Bowtell, David/H-1007-2016; Kerin, Michael/D-6748-2013; Ekici, Arif/C-3971-2013; Andrulis, Irene/E-7267-2013; Radice, Paolo/O-3119-2013; Knight, Julia/A-6843-2012; Dork, Thilo/J-8620-2012; Bernard, Loris/K-5953-2014 OI Muranen, Taru/0000-0002-5895-1808; Nevanlinna, Heli/0000-0002-0916-2976; dos Santos Silva, Isabel/0000-0002-6596-8798; Cox, Angela/0000-0002-5138-1099; Dunning, Alison Margaret/0000-0001-6651-7166; Giles, Graham/0000-0003-4946-9099; Arndt, Volker/0000-0001-9320-8684; Bruning, Thomas/0000-0001-9560-5464; Brenner, Hermann/0000-0002-6129-1572; manoukian, siranoush/0000-0002-6034-7562; Hollestelle, Antoinette/0000-0003-1166-1966; Schoemaker, Minouk/0000-0001-8403-2234; Golatta, Michael/0000-0002-2605-0060; Czene, Kamila/0000-0002-3233-5695; Cross, Simon/0000-0003-2044-1754; Li, Jingmei/0000-0001-8587-7511; laurent-puig, pierre/0000-0001-8475-5459; Bowtell, David/0000-0001-9089-7525; FU ABCFS: National Health and Medical Research Council of Australia; New South Wales Cancer Council; Victorian Health Promotion Foundation (Australia); United States (US) National Cancer Institute, NIH [RFA CA 06 503]; University of Melbourne [U01 CA69638]; ABCS: Dutch Cancer Society [NKI 2001-2423, 2007-3839]; Dutch National Genomics Initiative; ACP: Breast Cancer Research Trust, UK; BBCC: ELAN program of the University Hospital of Erlangen; Cancer Research UK [C150/A5660, C1178/A3947]; NHS; UK Medical Research Council [G0801414]; BCAC: Cancer Research UK [C1287/A10118, C1287/A12014]; European Community's Seventh Framework Programme [223175, HEALTH-F2-2009-223175]; European Union COST program [BM0606]; BIGGS: NIHR Comprehensive Biomedical Research Centre; Guy's & St. Thomas' NHS Foundation Trust in partnership with King's College London; Oxford Biomedical Research Centre; BSUCH: Helmholtz Society; German Cancer Research Center; Dietmar-Hopp Foundation; CECILE: Fondation de France [2004012618, 2007005156]; Institut National du Cancer (INCa) [2007-1/SPC2, 2008-1-CP-4, 2009-1-SHS/SP-04]; Association pour la Recherche contre le Cancer (ARC) [2008-1-CP-4]; Agence Francaise de Securite Sanitaire de l'Environnement et du Travail (AFSSET - ANSES) [ST-2005-003, EST2008/1/26, VS-2009-21]; Ligue contre le Cancer Grand Ouest; Agence Nationale de la Recherche (ANR) [00047-05]; CGPS: Herlev Hospital; Chief Physician Johan Boserup; Lise Boserup's Fund; CNIO-BCS: Genome Spain Foundation; Red Tematica de Investigacion Cooperativa en Cancer; Asociacion Espanola Contra el Cancer; Fondo de Investigacion Sanitario [PI081583, PI081120]; CTS: California Breast Cancer Act; NIH [R01 CA77398]; Lon V Smith Foundation [LVS39420]; California Breast Cancer Research Fund [97-10500]; California Department of Public Health; Deutsche Krebshilfe (German Cancer Aid); GESBC: Deutsche Krebshilfe e.V. [70492]; Baden-Wurttemberg through the Medical Faculty of the University of Ulm [P.685]; GC-HBOC: Deutsche Krebshilfe [107054]; Helmholtz society; German Cancer Research Centre (DKFZ); GENICA: Federal Ministry of Education and Research (BMBF) Germany [01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114]; Robert Bosch Foundation, Stuttgart; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg; Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn; Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum, Germany; HABCS: Rudolf Bartling Foundation; HEBCS: Helsinki University Central Hospital Research Fund, Academy of Finland [132473]; Finnish Cancer Society; Nordic Cancer Union; Sigrid Juselius Foundation; HMBCS: Hannelore Munke Stipend; HUBCS: German Federal Ministry for Research and Education [RUS 08/017]; KARBAC: Swedish Cancer Society; Stockholm Cancer Society; Gustav V Jubilee Foundation; KBCP: Finnish Cancer Society; Academy of Finland [127220]; Government Funding (EVO) of Kuopio University Hospital [5654113, 5501]; University of Eastern Finland; KConFab-AOCS: National Breast Cancer Foundation; National Health and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria, Tasmania and South Australia; Cancer Foundation of Western Australia; NHMRC [145684, 288704, 454508, 199600]; US Army Medical Research and Materiel Command [DAMD17-01-1-0729]; Cancer Council of Tasmania; LMBC: 'Stichting tegen Kanker' [232-2008, 196-2010]; MARIE: Deutsche Krebshilfe e.V. [70-2892-BR 1]; Hamburg Society; Federal Ministry of Education and Research (BMBF) Germany [01KH0402]; MBCSG: Ministero della Salute (Extraordinary National Cancer Program "Alleanza contro il Cancro"); MBCSG: Ministero della Salute (Extraordinary National Cancer Program "Progetto Tumori Femminili"); Ministero dell'Universita e Ricerca (RBLAO3-BETH); Fondazione Italiana per la Ricerca sul Cancro (Special Project "Hereditary tumors"); Associazione Italiana per la Ricerca sul Cancro [4017]; Fondazione IRCCS Istituto Nazionale Tumori; MCBCS: NIH [CA122340]; Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]; Komen Foundation for the Cure; Breast Cancer Research Foundation (BCRF); MCCS: Australian National Health and Medical Research Council [209057, 251533, 396414, 504711]; Cancer Council Victoria; VicHealth; NC-BCFR: US National Cancer Institute, NIH [RFA-CA-06-503]; Cancer Care Ontario [U01 CA69467]; Cancer Prevention Institute of California [U01 CA69417]; OBCS: Finnish Cancer Foundation; Academy of Finland; University of Oulu; Oulu University Hospital; OFBCR: US National Cancer Institute, NIH [RFA-CA-06503]; Northern California Cancer Center [U01 CA69417]; Cancer Care Ontario; ORIGO: Dutch Cancer Society [RUL 1997-1505]; Biobanking and Biomolecular Resources Research Infrastructure [BBMRI-NL CP16]; RBCS: Dutch Cancer Society [DDHK 2004-3124, DDHK 2009-4318]; SASBAC: NIH [RO1 CA58427]; Agency for Science, Technology and Research (A *STAR; Singapore); SBCS: Yorkshire Cancer Research; Breast Cancer Campaign; SEARCH: Programme grant from Cancer Research UK [C490/A10124]; UCIBCS: US NIH [CA58860, CA92044]; UKBGS: Breakthrough Breast Cancer FX This work was supported by the following sources - ABCFS: National Health and Medical Research Council of Australia, the New South Wales Cancer Council; the Victorian Health Promotion Foundation (Australia); the United States (US) National Cancer Institute, NIH [RFA CA 06 503]; and through cooperative agreements with members of the Breast Cancer Family Registry (CFR) and principal investigators. The University of Melbourne [U01 CA69638] contributed data to this study. ABCS: Dutch Cancer Society [NKI 2001-2423, 2007-3839] and Dutch National Genomics Initiative. ACP: Breast Cancer Research Trust, UK. BBCC: ELAN program of the University Hospital of Erlangen. BBCS: Cancer Research UK [C150/A5660 and C1178/A3947]; Break through Breast Cancer; and NHS funding to the NIHR Biomedical Research Centre and the National Cancer Research Network (NCRN). H. Warren is funded by the UK Medical Research Council [G0801414]. BCAC: Cancer Research UK [C1287/A10118, C1287/A12014] and the European Community's Seventh Framework Programme under grant agreement no. 223175 (HEALTH-F2-2009-223175) (COGS). BCAC meetings have been funded by the European Union COST program [BM0606]. BIGGS: NIHR Comprehensive Biomedical Research Centre, Guy's & St. Thomas' NHS Foundation Trust in partnership with King's College London [to E.J. Sawyer]; Oxford Biomedical Research Centre (to I. Tomlinson]. BSUCH: Helmholtz Society; German Cancer Research Center; and Dietmar-Hopp Foundation. CECILE: Fondation de France [2004012618, 2007005156]; Institut National du Cancer (INCa) [2007-1/SPC2, 2008-1-CP-4, 2009-1-SHS/SP-04]; Association pour la Recherche contre le Cancer (ARC) [2008-1-CP-4]; Agence Francaise de Securite Sanitaire de l'Environnement et du Travail (AFSSET - ANSES) [ST-2005-003, EST2008/1/26, and VS-2009-21]; Ligue contre le Cancer Grand Ouest; and Agence Nationale de la Recherche (ANR) [00047-05]. CGPS: Herlev Hospital; Chief Physician Johan Boserup; and Lise Boserup's Fund. CNIO-BCS: Genome Spain Foundation; the Red Tematica de Investigacion Cooperativa en Cancer and grants from the Asociacion Espanola Contra el Cancer; and the Fondo de Investigacion Sanitario [PI081583, PI081120]. CTS: California Breast Cancer Act of 1993; NIH [R01 CA77398]; the Lon V Smith Foundation [LVS39420]; and the California Breast Cancer Research Fund [contract 97-10500]. Collection of cancer incidence data used in this study was supported by the California Department of Public Health as part of the statewide cancer-reporting program mandated by California Health and Safety Code Section 103885. ESTHER: Baden-Wurttemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study that was supported by a grant from the Deutsche Krebshilfe (German Cancer Aid). GESBC: Deutsche Krebshilfe e.V. [70492]; and genotyping in part by the state of Baden-Wurttemberg through the Medical Faculty of the University of Ulm [P.685]. GC-HBOC: Deutsche Krebshilfe [107054]; the Dietmar-Hopp Foundation; the Helmholtz society; and the German Cancer Research Centre (DKFZ). GENICA: Federal Ministry of Education and Research (BMBF) Germany [01KW9975/5, 01KW9976/8, 01KW9977/0, 01KW0114]; Robert Bosch Foundation, Stuttgart; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg; Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn; Institute for Prevention and Occupational Medicine of the German Social Accident Insurance (IPA), Bochum, Germany. HABCS: Rudolf Bartling Foundation.; HEBCS: Helsinki University Central Hospital Research Fund, Academy of Finland [132473]; Finnish Cancer Society; Nordic Cancer Union; and Sigrid Juselius Foundation. HMBCS: Hannelore Munke Stipend [to N. Bogdanova]. HUBCS: German Federal Ministry for Research and Education [RUS 08/017]. KARBAC: Swedish Cancer Society; Stockholm Cancer Society; and Gustav V Jubilee Foundation. KBCP: Finnish Cancer Society; Academy of Finland [127220], special Government Funding (EVO) of Kuopio University Hospital [5654113, 5501]; and strategic funding from the University of Eastern Finland. KConFab-AOCS: National Breast Cancer Foundation; National Health and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer Councils of New South Wales, Victoria, Tasmania and South Australia; and the Cancer Foundation of Western Australia. The kConFab Clinical Follow Up Study was funded by the NHMRC [145684, 288704, 454508]. Financial support for the AOCS was provided by the US Army Medical Research and Materiel Command [DAMD17-01-1-0729], the Cancer Council of Tasmania and Cancer Foundation of Western Australia and the NHMRC [199600]. G. Chenevix-Trench and P. Webb are supported by the NHMRC. LMBC: 'Stichting tegen Kanker' [232-2008, 196-2010]. MARIE: Deutsche Krebshilfe e.V. [70-2892-BR 1]; Hamburg Society; German Cancer Research Center; and the genotype work in part by the Federal Ministry of Education and Research (BMBF) Germany [01KH0402]. MBCSG: Ministero della Salute (Extraordinary National Cancer Program 2006 "Alleanza contro il Cancro", and "Progetto Tumori Femminili") (to P. Radice); Ministero dell'Universita e Ricerca (RBLAO3-BETH; to P. Radice); Fondazione Italiana per la Ricerca sul Cancro (Special Project "Hereditary tumors"); Associazione Italiana per la Ricerca sul Cancro (4017; to P. Peterlongo) and by funds from Italian citizens who allocated the 5/1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional strategic projects "5 x 1000"). MCBCS: NIH [CA122340]; Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]; the Komen Foundation for the Cure; and the Breast Cancer Research Foundation (BCRF). MCCS: Australian National Health and Medical Research Council [209057, 251533, 396414, 504711], with infrastructure support provided by the Cancer Council Victoria, and cohort recruitment partly funded by VicHealth. NC-BCFR: US National Cancer Institute, NIH [RFA-CA-06-503] and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators, including Cancer Care Ontario [U01 CA69467], the Cancer Prevention Institute of California [U01 CA69417], and The University of Melbourne [U01 CA69638]. Samples from the NC-BCFR were processed and distributed by the Coriell Institute for Medical Research. OBCS: Finnish Cancer Foundation; Academy of Finland; University of Oulu; and Oulu University Hospital. OFBCR: US National Cancer Institute, NIH [RFA-CA-06503] and through cooperative agreements with members of the Breast Cancer Family Registry (BCFR) and Principal Investigators, including Cancer Care Ontario [U01 CA69467], Northern California Cancer Center [U01 CA69417], and University of Melbourne [U01 CA69638] and by Cancer Care Ontario. ORIGO: Dutch Cancer Society [RUL 1997-1505]; and Biobanking and Biomolecular Resources Research Infrastructure [BBMRI-NL CP16]. RBCS: Dutch Cancer Society [DDHK 2004-3124, DDHK 2009-4318]. SASBAC: NIH [RO1 CA58427] [to P. Hillemanns and J.; Liu]; and the Agency for Science, Technology and Research (A *STAR; Singapore). SBCS: Yorkshire Cancer Research; and Breast Cancer Campaign. SEARCH: Programme grant from Cancer Research UK [C490/A10124]. UCIBCS: US NIH [CA58860, CA92044] and the Lon V Smith Foundation [LVS39420]. UKBGS: Breakthrough Breast Cancer. NR 26 TC 11 Z9 11 U1 2 U2 24 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2012 VL 21 IS 10 BP 1783 EP 1791 DI 10.1158/1055-9965.EPI-12-0526 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 017FS UT WOS:000309576100022 PM 22859399 ER PT J AU Phipps, AI Buchanan, DD Makar, KW Burnett-Hartman, AN Coghill, AE Passarelli, MN Baron, JA Ahnen, DJ Win, AK Potter, JD Newcomb, PA AF Phipps, Amanda I. Buchanan, Daniel D. Makar, Karen W. Burnett-Hartman, Andrea N. Coghill, Anna E. Passarelli, Michael N. Baron, John A. Ahnen, Dennis J. Win, Aung Ko Potter, John D. Newcomb, Polly A. TI BRAF Mutation Status and Survival after Colorectal Cancer Diagnosis According to Patient and Tumor Characteristics SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ISLAND METHYLATOR PHENOTYPE; MICROSATELLITE INSTABILITY; COLON-CANCER; MISMATCH REPAIR; V600E MUTATION; POOR SURVIVAL; MOLECULAR-FEATURES; STAGE-II; RISK; IMMUNOHISTOCHEMISTRY AB Background: BRAF mutations in colorectal cancer (CRC) are disproportionately observed in tumors exhibiting microsatellite instability (MSI) and are associated with other prognostic factors. The independent association between BRAF mutation status and CRC survival, however, remains unclear. Methods: We evaluated the association between the BRAF c.1799T>A (p.V600E) mutation and survival in individuals with incident invasive CRC diagnosed between 1997 and 2007 in Western Washington State. Tumor specimens were tested for this BRAF mutation and MSI status. We used Cox regression to estimate HRs and 95% confidence intervals (CI) for the association between BRAF mutation status and disease-specific and overall survival. Stratified analyses were conducted by age, sex, tumor site, stage, and MSI status. Results: Among 1,980 cases tested, 12% were BRAF c.1799T>A(p.V600E) mutation-positive (n = 247). BRAF-mutated CRC was associated with poorer disease-specific survival adjusting for age, sex, time from diagnosis to enrollment, stage, and MSI status (HR, 1.43; 95% CI, 1.05-1.95). This association was limited to cases diagnosed at ages <50 (HR, 3.06; 95% CI, 1.70-5.52) and was not evident in cases with MSI-high tumors (HR, 0.94; 95% CI, 0.44-2.03). Associations with overall survival were similar. Conclusions: Our results show that the prevalence of BRAF mutations in CRC differs by patient and tumor characteristics and suggest that the association between BRAF status and CRC survival may differ by some of these factors. Impact: The presence of a BRAF c.1799T>A (p.V600E) mutation is associated with significantly poorer prognosis after CRC diagnosis among subgroups of patients. Cancer Epidemiol Biomarkers Prev; 21(10); 1792-8. (c) 2012 AACR. C1 [Phipps, Amanda I.; Makar, Karen W.; Burnett-Hartman, Andrea N.; Coghill, Anna E.; Passarelli, Michael N.; Potter, John D.; Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Buchanan, Daniel D.] Queensland Inst Med Res, Familial Canc Lab, Brisbane, Qld 4006, Australia. [Baron, John A.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Ahnen, Dennis J.] Univ Colorado, Sch Med, Denver Vet Affairs Med Ctr, Denver, CO USA. [Win, Aung Ko] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Parkville, Vic 3052, Australia. [Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand. RP Phipps, AI (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,M4-B402, Seattle, WA 98109 USA. EM aphipps@fhcrc.org OI Potter, John/0000-0001-5439-1500; Win, Aung Ko/0000-0002-2794-5261; Buchanan, Daniel/0000-0003-2225-6675 FU National Cancer Institute (NCI), NIH [U01CA74794, R01CA076366]; NCI [R25-CA94880, K05 CA152715] FX This work was supported by the National Cancer Institute (NCI), NIH (U01CA74794, R01CA076366), and through cooperative agreements with members of the Colon Cancer Family Registry and Principal Investigators. This publication was also supported by the NCI grant R25-CA94880 and NCI grant K05 CA152715. NR 48 TC 54 Z9 55 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2012 VL 21 IS 10 BP 1792 EP 1798 DI 10.1158/1055-9965.EPI-12-0674 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 017FS UT WOS:000309576100023 PM 22899730 ER PT J AU Chan, JM Litwack-Harrison, S Bauer, SR Daniels, NA Wilt, TJ Shannon, J Bauer, DC AF Chan, June M. Litwack-Harrison, Stephanie Bauer, Scott R. Daniels, Nicholas A. Wilt, Timothy J. Shannon, Jackilen Bauer, Douglas C. TI Statin Use and Risk of Prostate Cancer in the Prospective Osteoporotic Fractures in Men (MrOS) Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID POPULATION AB Background: Statins are a common medication for cholesterol control that may also have effects on cancer-related pathways. The evidence of an association between statins and prostate cancer risk remains ambiguous. Methods: We examined statin use in a prospective cohort of 5,069 elderly U.S. men and the risk of incident total, low/high stage, and low/high grade prostate cancer diagnosed between 2000 and 2008. We used multivariate logistic regression models to estimate relative risks and 95% confidence intervals, adjusting for demographic and lifestyle characteristics. Results: There was no evidence of an association between statin use and any of the prostate cancer endpoints (total, low/high stage, low/high grade prostate cancer), adjusting for age, study site, race, body mass index, marital status, family history of prostate cancer, number of comorbidities, physical activity, and smoking history. Conclusions and Impact: In this study of elderly U. S. men, we observed a null association between statin use and risk of prostate cancer. Cancer Epidemiol Biomarkers Prev; 21(10); 1886-8. (c) 2012 AACR. C1 [Chan, June M.; Bauer, Scott R.; Wilt, Timothy J.; Bauer, Douglas C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94158 USA. [Chan, June M.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94158 USA. [Litwack-Harrison, Stephanie; Daniels, Nicholas A.; Bauer, Douglas C.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94158 USA. [Shannon, Jackilen] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Shannon, Jackilen] Portland VA Med Ctr, Portland, OR USA. RP Chan, JM (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, 1450 3rd St,MC 3110, San Francisco, CA 94158 USA. EM june.chan@ucsf.edu FU National Institutes of Health; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Institute on Aging (NIA); National Center for Research Resources (NCRR); NIH Roadmap for Medical Research [U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, UL1 RR024140]; Prostate Cancer Foundation; Steven & Christine Burd-Safeway Endowment FX The MrOS Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute on Aging (NIA), the National Center for Research Resources (NCRR), and NIH Roadmap for Medical Research under the following grant numbers: U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, and UL1 RR024140. Dr. Chan and Mr. S. Bauer also receive support from the Prostate Cancer Foundation and the Steven & Christine Burd-Safeway Endowment. NR 8 TC 5 Z9 5 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2012 VL 21 IS 10 BP 1886 EP 1888 DI 10.1158/1055-9965.EPI-12-0816 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 017FS UT WOS:000309576100034 PM 22879205 ER PT J AU Mendez, E AF Mendez, Eduardo TI Biomarkers of HPV Infection in Oropharyngeal Carcinomas: Can We Find Simplicity in the Puzzle of Complexity? SO CANCER RESEARCH LA English DT Review ID SQUAMOUS-CELL CARCINOMA; ONCOGENIC HUMAN-PAPILLOMAVIRUS; UNITED-STATES; COPY NUMBER; NECK-CANCER; ORAL-CAVITY; HEAD; SURVIVAL; P16(INK4A); PREVALENCE C1 [Mendez, Eduardo] Univ Washington, Fred Hutchinson Canc Res Ctr, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98109 USA. [Mendez, Eduardo] VA Puget Sound Hlth Care Syst, Surg & Perioperat Care Serv, Seattle, WA USA. [Mendez, Eduardo] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. RP Mendez, E (reprint author), Univ Washington, Fred Hutchinson Canc Res Ctr, Dept Otolaryngol Head & Neck Surg, 1100 Fairview Ave N,Mail Stop D5-390, Seattle, WA 98109 USA. EM edmendez@uw.edu NR 22 TC 3 Z9 3 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2012 VL 72 IS 19 BP 4896 EP 4898 DI 10.1158/0008-5472.CAN-12-3285 PG 3 WC Oncology SC Oncology GA 016LY UT WOS:000309521200004 PM 22991303 ER PT J AU Liang, CH Marsit, CJ McClean, MD Nelson, HH Christensen, BC Haddad, RI Clark, JR Wein, RO Grillone, GA Houseman, EA Halec, G Waterboer, T Pawlita, M Krane, JF Kelsey, KT AF Liang, Caihua Marsit, Carmen J. McClean, Michael D. Nelson, Heather H. Christensen, Brock C. Haddad, Robert I. Clark, John R. Wein, Richard O. Grillone, Gregory A. Houseman, E. Andres Halec, Gordana Waterboer, Tim Pawlita, Michael Krane, Jeffrey F. Kelsey, Karl T. TI Biomarkers of HPV in Head and Neck Squamous Cell Carcinoma SO CANCER RESEARCH LA English DT Article ID HUMAN-PAPILLOMAVIRUS INFECTION; GLUTATHIONE-S-TRANSFERASE; PROGNOSTIC-SIGNIFICANCE; OROPHARYNGEAL CANCER; CERVICAL-CARCINOMA; NATURAL-HISTORY; SEXUAL-BEHAVIOR; ORAL-CANCER; P16 PROTEIN; ROC CURVES AB Human papillomavirus (HPV) is an accepted cause of head and neck squamous cell carcinoma (HNSCC), and patients with HPV-associated HNSCC have a favorable prognosis. Currently, there is no general guidance on the most appropriate biomarkers for clinical assessment of HPV in these malignancies. We compared PCR-based and serologic HPV assays, as well as p16 immunohistochemistry, individually and in combination in a single population-based study to assess their associations with overall survival among patients with HNSCC, and thus their potential value as biomarkers. HPV16 serology was determined for 488 patients; immunohistochemical detection of p16 expression in tumors was conducted in a subset of 233 cases, and PCR-based methods to assess the presence of HPV16 DNA in a subset of 179 cases of tumors. Considering each biomarker individually in the subset of patients studied for all endpoints, seropositivity for the E6 and E7 proteins was significantly associated with enhanced all-cause survival in oropharyngeal disease [HRE6/E7+ = 0.1, 95% confidence interval (CI) = 0.02-0.3]. Neither the presence of HPV16 DNA nor p16 immunostaining was associated with significant enhanced overall survival in oropharyngeal disease (HRDNA = 0.9, 95% CI = 0.3-2.9; HRp16 = 0.3, 95% CI = 0.1-1.1). However, the combination of HPV-positive DNA and E6 or E7 serology was associated with enhanced overall survival in oropharyngeal disease (HRDNA+/E6/E7+ = 0.1, 95% CI = 0.02-1.0), whereas E6/E7 seronegative patients with evidence of HPV in tumor DNA did not show any evidence of favorable survival (HRDNA+/E6-/E7- = 3.4, 95% CI = 0.6-18.1). Furthermore, patients with p16 staining and E6 or E7 seropositivity had favorable survival from oropharyngeal disease (HRp16+/E6/E7+ = 0.1, 95% CI = 0.02-0.4), whereas patients who were p16 positive and E6/E7 seronegative had significantly increased hazard of all causes of death (HRp16+/E6-/E7- = 3.1, 95% CI = 1.2-7.7). A stronger association of HPV presence with prognosis (assessed by all-cause survival) is observed when "HPV-associated" HNSCC is defined using tumor status (HPV DNA status or P16) and HPV E6/E7 serology in combination rather using tumor HPV status alone. Cancer Res; 72(19); 5004-13. (C)2012 AACR. C1 [Liang, Caihua; Kelsey, Karl T.] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA. [Kelsey, Karl T.] Brown Univ, Dept Pathol & Lab Med, Div Biol & Med, Providence, RI 02912 USA. [Marsit, Carmen J.; Christensen, Brock C.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Pharmacol & Toxicol, Hanover, NH 03756 USA. [Marsit, Carmen J.; Christensen, Brock C.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH 03756 USA. [McClean, Michael D.] Boston Univ, Dept Environm Hlth, Sch Publ Hlth, Boston, MA 02215 USA. [Haddad, Robert I.] Dana Farber Canc Inst, Dept Med Oncol Solid Tumor Oncol, Boston, MA USA. [Clark, John R.] Massachusetts Gen Hosp, Dept Med Hematol Oncol, Boston, MA 02114 USA. [Wein, Richard O.] Tufts Med Ctr, Dept Otolaryngol Head & Neck Surg, Boston, MA USA. [Grillone, Gregory A.] Boston Univ, Dept Otolaryngol Head & Neck Surg, Med Ctr, Boston, MA USA. [Krane, Jeffrey F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Nelson, Heather H.] Univ Minnesota, Masonic Canc Ctr, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Houseman, E. Andres] Oregon State Univ, Coll Publ Hlth & Human Sci, Corvallis, OR 97331 USA. [Halec, Gordana; Waterboer, Tim; Pawlita, Michael] Deutsch Krebsforschungszentrum, Infect & Canc Program, German Canc Res Ctr, D-6900 Heidelberg, Germany. RP Kelsey, KT (reprint author), Brown Univ, Dept Epidemiol, Providence, RI 02912 USA. EM Karl_Kelsey@brown.edu RI Pawlita, Labor/C-9720-2011; Kelsey, Karl/I-1252-2014; McClean, Michael/J-2934-2015; Waterboer, Tim/G-1252-2010; OI Pawlita, Michael/0000-0002-4720-8306; Marsit, Carmen/0000-0003-4566-150X; McClean, Michael/0000-0002-3902-8823; Houseman, Eugene Andres/0000-0003-0703-1830 FU NIH [CA078609, CA100679]; Flight Attendants Medical Research Institute FX This work was supported by the NIH [CA078609 and CA100679] and Flight Attendants Medical Research Institute. NR 50 TC 58 Z9 58 U1 1 U2 12 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2012 VL 72 IS 19 BP 5004 EP 5013 DI 10.1158/0008-5472.CAN-11-3277 PG 10 WC Oncology SC Oncology GA 016LY UT WOS:000309521200015 PM 22991304 ER PT J AU Counter, SA Buchanan, LH Ortega, F AF Counter, S. Allen Buchanan, Leo H. Ortega, Fernando TI Association of hemoglobin levels and brainstem auditory evoked responses in lead-exposed children SO CLINICAL BIOCHEMISTRY LA English DT Article DE Hemoglobin; Brainstem auditory evoked responses; Anemia; Lead exposure ID ANDEAN CHILDREN; BLOOD LEAD; ZINC PROTOPORPHYRIN; ANEMIA; POTENTIALS; INFANTS; NEWBORN; WORKERS; IRON AB Objectives: Decreased blood hemoglobin (HbB) levels and anemia have been associated with abnormal brainstem auditory evoked responses (BAER). Lead (Pb) exposure has also been associated with anemia and aberrant BAER. This study investigated the relationship between HbB level and BAER wave latency and amplitude in Pb-exposed Andean children. Design and methods: Sixty-six children aged 2 to 15 years (mean age: 9.1; SD: 3.3) living in Pb-contaminated villages were screened for HbB levels, blood Pb (PbB) levels and BAER latencies and amplitudes. Results:The mean HbB level observed in the study group was 11.9 g/dL (SD: 1.4; range: 8.6-14.8 g/dL). The mean HbB level corrected for altitude was 10.3 g/dL (SD: 1.4; range: 6.9-13.1 g/dL), and suggestive of anemia. The mean PbB level was 49.3 mu g/dL (SD: 30.1; range: 4.4-119.1 mu g/dL) and indicative of Pb poisoning. Spearman rho correlation analyses revealed significant associations between the BAER absolute latencies and HbB level, indicating that as the HbB level decreased, the BAER wave latency increased. Children with low HbB levels (<= 11 g/dL) showed significantly prolonged absolute latencies of waves I,II,III, IV and V compared to the children with normal HbB levels. Although a significant relationship between HbB and BAER waves was observed, no significant associations between PbB level and BAER parameters were found. Conclusion: Low hemoglobin levels may diminish auditory sensory-neural function, and is therefore an important variable to consider when assessing BAER in children with anemia and/or Pb exposure. (C) 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. C1 [Counter, S. Allen] Harvard Univ, Sch Med, Dept Neurol, Biol Labs, Cambridge, MA 02138 USA. [Counter, S. Allen] Massachusetts Gen Hosp, Dept Neurophysiol, Boston, MA 02114 USA. [Buchanan, Leo H.] Univ Massachusetts, Sch Med, Eunice Kennedy Shriver Ctr, Dept Pediat, Waltham, MA USA. [Buchanan, Leo H.] Harvard Univ, Hlth Serv, Dept Otolaryngol, Cambridge, MA 02138 USA. [Ortega, Fernando] Univ San Francisco Quito, Coll Hlth Sci, Integrated Community Dev Dept, Quito, Ecuador. RP Counter, SA (reprint author), Harvard Univ, Sch Med, Dept Neurol, Biol Labs, 16 Divin Ave, Cambridge, MA 02138 USA. EM allen_counter@harvard.edu FU Harvard Biological Laboratories; Harvard University Health Services FX The authors thank Dr. Mauricio Espinel, Dean of Universidad San Francisco de Quito Medical School, Dr. Jose Izurieta, Director of Health, Cotopaxi Province, Dr. Galo Tapia, Director, Pujili Hospital, Dr. Cecilia Zambrano, Director, La Victoria Subcentro de Salud, Ms. Gladys Pacheco, Nurse, Subcentro de Salud, La Victoria, and the Universidad San Francisco de Quito Medical School for continued support of this project. The authors are also grateful to Dr. Nader Rifai, Ms. Patricia Nolan Hoover and Mr. Gary Bradwin, Boston Children's Hospital Medical Laboratories for laboratory support. Anthony B. Jacobs is thanked for excellent technical assistance. The authors are grateful to Dr. Merilee Grindle, Director of the David Rockefeller Center for Latin American Studies at Harvard; Dr. Jeremy Bloxham, Dean of Science, Harvard University; Harvard Biological Laboratories and Harvard University Health Services for support. NR 28 TC 7 Z9 7 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0009-9120 J9 CLIN BIOCHEM JI Clin. Biochem. PD OCT PY 2012 VL 45 IS 15 BP 1197 EP 1201 DI 10.1016/j.clinbiochem.2012.06.020 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 017ZZ UT WOS:000309631000015 PM 22735387 ER PT J AU Ibrahimi, OA Bangash, H Green, L Alam, M Armstrong, AW Eisen, DB AF Ibrahimi, Omar A. Bangash, Haider Green, Lawrence Alam, Murad Armstrong, April W. Eisen, Daniel B. TI Perceptions of Expertise in Cutaneous Surgery and Cosmetic Procedures: What Primary Care Physicians Think SO DERMATOLOGIC SURGERY LA English DT Article ID PHOTOTHERMOLYSIS AB Background Primary care physician (PCP) perceptions regarding expertise in cutaneous surgery and cosmetic procedures are unknown. Methods An internet-based survey was administered to physicians in primary care medicine residency programs in the United States. Respondents were asked to select the specialist most qualified to perform different cutaneous cosmetic and surgical procedures. Results Five hundred sixty-one PCPs undertook the survey. Dermatologists were identified as the most qualified specialist to evaluate and biopsy worrisome lesions on the face (95%), perform skin cancer surgery (56%), inject botulinum toxin (61%), inject fillers (55%), and perform laser procedures (75%). Seventy percent of respondents correctly defined Mohs micrographic surgery (MMS), and 60% of respondents selected a fellowship-trained dermatologist as the best physician to perform MMS. U.S. medical school graduates were more likely than foreign medical school graduates to select a Mohs fellowshiptrained dermatologist as the most qualified physician to perform MMS (adjusted odds ratio (AOR) = 1.52, 95% confidence interval (CI) = 1.052.21). PCPs without exposure to dermatology in medical school were about half as likely those with exposure to correctly define MMS (AOR = 0.51, 95% CI = 0.300.89). Conclusions Dermatologists are recognized as the most qualified specialist to perform a variety of cutaneous cosmetic and surgical procedures, including skin cancer surgery, botulinum toxin injections, filler injections, and laser procedures. Mohs fellowshiptrained dermatologists were viewed as more qualified to perform MMS than other dermatologists, plastic surgeons, otolaryngologists, or ophthalmologists. C1 [Ibrahimi, Omar A.] Connecticut Skin Inst, Stamford, CT USA. [Ibrahimi, Omar A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Bangash, Haider] Univ Connecticut, Ctr Hlth, Dept Internal Med, Farmington, CT USA. [Green, Lawrence] George Washington Univ, Sch Med, Dept Dermatol, Washington, DC USA. [Alam, Murad] Northwestern Univ, Dept Dermatol, Chicago, IL 60611 USA. [Armstrong, April W.; Eisen, Daniel B.] Univ Calif Davis, Dept Dermatol, Sacramento, CA 95817 USA. RP Ibrahimi, OA (reprint author), 999 Summer St, Stamford, CT 06905 USA. EM omar.ibrahimi@gmail.com OI Eisen, Daniel/0000-0001-6741-3182 FU American Society for Dermatologic Surgery FX This study was supported by a Cutting Edge Research Grant from the American Society for Dermatologic Surgery. NR 11 TC 12 Z9 12 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD OCT PY 2012 VL 38 IS 10 BP 1645 EP 1651 DI 10.1111/j.1524-4725.2012.02577.x PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 015PZ UT WOS:000309459700008 PM 22958115 ER PT J AU Ortiz, AE Avram, MM AF Ortiz, Arisa E. Avram, Mathew M. TI Redistribution of Ink After Laser Tattoo Removal SO DERMATOLOGIC SURGERY LA English DT Editorial Material C1 [Avram, Mathew M.] Massachusetts Gen Hosp, Dermatol Laser & Cosmet Ctr, Boston, MA 02114 USA. [Ortiz, Arisa E.] Univ Calif Irvine, Dept Dermatol, Irvine, CA 92717 USA. RP Avram, MM (reprint author), Massachusetts Gen Hosp, Dermatol Laser & Cosmet Ctr, 50 Staniford St,Suite 250, Boston, MA 02114 USA. EM mavram@partners.org NR 3 TC 3 Z9 3 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1076-0512 EI 1524-4725 J9 DERMATOL SURG JI Dermatol. Surg. PD OCT PY 2012 VL 38 IS 10 BP 1730 EP 1731 DI 10.1111/j.1524-4725.2012.02560.x PG 2 WC Dermatology; Surgery SC Dermatology; Surgery GA 015PZ UT WOS:000309459700023 PM 22913481 ER PT J AU Messlinger, K Lennerz, JK Eberhardt, M Fischer, MJM AF Messlinger, Karl Lennerz, Jochen K. Eberhardt, Mirjam Fischer, Michael J. M. TI CGRP and NO in the Trigeminal System: Mechanisms and Role in Headache Generation SO HEADACHE LA English DT Review DE calcitonin gene-related peptide; nitric oxide; headache; dura mater; trigeminal ganglion; trigeminal nucleus ID GENE-RELATED PEPTIDE; NITRIC-OXIDE SYNTHASE; RAT DURA-MATER; TENSION-TYPE HEADACHE; MENINGEAL BLOOD-FLOW; RECEPTOR ANTAGONIST BIBN4096BS; ACTIVITY-MODIFYING PROTEIN-1; INDUCED MIGRAINE ATTACK; NERVE-FIBERS; SUBSTANCE-P AB Calcitonin gene-related peptide (CGRP) and metabolic products of nitric oxide (NO) are increased in jugular venous plasma during migraine attacks and other primary headaches. Patients suffering from primary headaches are particularly sensitive to CGRP and NO donors responding with delayed headaches to an infusion of either of these substances. Accordingly, both CGRP and NO are considered as key mediators in migraine, and clinical trials have shown that inhibitors of CGRP receptors and NO synthase are effective in treating migraine. There is an implicit understanding that CGRP and NO systems interact, and here, we review the body of preclinical work on these systems focusing on the trigeminovascular system in migraine. NO derives from various cell types via 3 isoforms of NO synthase, whereas CGRP is produced from a subset of trigeminal afferents. In rodents, NO donors cause activity alterations on different levels of the trigeminal system including enhancement of CGRP release, which in turn results in arterial vasodilatation and possibly mast cell degranulation in the meninges. The activity of spinal trigeminal neurons, which is a sensitive integrative measure for trigeminal activity, is partly under the control of CGRP and NO. Both mediators facilitate nociceptive transmission, possibly via presynaptic mechanisms. These functions are supported by immunolocalization of CGRP receptor components on 3 trigeminovascular levels: cranial dura mater, trigeminal ganglion, and spinal trigeminal nucleus. Current data support a relationship of CGRP and NO actions on all levels of the trigeminovascular system and emphasize central CGRP receptors as possible therapeutic targets. C1 [Messlinger, Karl; Eberhardt, Mirjam; Fischer, Michael J. M.] Univ Erlangen Nurnberg, Inst Physiol & Pathophysiol, D-91054 Erlangen, Germany. [Lennerz, Jochen K.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Lennerz, Jochen K.] Univ Ulm, Inst Pathol, Ulm, Germany. [Fischer, Michael J. M.] Univ Cambridge, Dept Pharmacol, Cambridge CB2 1QJ, England. RP Messlinger, K (reprint author), Univ Erlangen Nurnberg, Inst Physiol & Pathophysiol, Univ Str 17, D-91054 Erlangen, Germany. FU Federal Ministry of Education and Research of the Federal Republic of Germany (German Headache Consortium); German Research Foundation [995/3-1]; Else-Kroner-Fresenius Foundation; University of Erlangen-Nurnberg (Emerging Fields Initiative Medicinal Redox Inorganic Chemistry) FX This review is based on projects supported by the Federal Ministry of Education and Research of the Federal Republic of Germany (German Headache Consortium) and the German Research Foundation (M.E. 995/3-1). The Else-Kroner-Fresenius Foundation supported J.K.L., and the University of Erlangen-Nurnberg (Emerging Fields Initiative Medicinal Redox Inorganic Chemistry) supported M.E. NR 132 TC 44 Z9 44 U1 1 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-8748 J9 HEADACHE JI Headache PD OCT PY 2012 VL 52 IS 9 BP 1411 EP 1427 DI 10.1111/j.1526-4610.2012.02212.x PG 17 WC Clinical Neurology SC Neurosciences & Neurology GA 015LE UT WOS:000309446600009 PM 22788114 ER PT J AU Seepersaud, R Bensing, BA Yen, YT Sullam, PM AF Seepersaud, Ravin Bensing, Barbara A. Yen, Yihfen T. Sullam, Paul M. TI The Accessory Sec Protein Asp2 Modulates GlcNAc Deposition onto the Serine-Rich Repeat Glycoprotein GspB SO JOURNAL OF BACTERIOLOGY LA English DT Article ID STREPTOCOCCUS-GORDONII; STRUCTURE PREDICTION; SURFACE PROTEIN; HUMAN PLATELETS; BINDING; GLYCOSYLATION; SYSTEM; EXPORT; ADHESIN; BIOGENESIS AB The accessory Sec system is a specialized transport system that exports serine-rich repeat (SRR) glycoproteins of Gram-positive bacteria. This system contains two homologues of the general secretory (Sec) pathway (SecA2 and SecY2) and several other essential proteins (Asp1 to Asp5) that share no homology to proteins of known function. In Streptococcus gordonii, Asp2 is required for the transport of the SRR adhesin GspB, but its role in export is unknown. Tertiary structure predictions suggest that the carboxyl terminus of Asp2 resembles the catalytic region of numerous enzymes that function through a Ser-Asp-His catalytic triad. Sequence alignment of all Asp2 homologues identified a highly conserved pentapeptide motif (Gly-X-Ser(362)-X-Gly) typical of most Ser-Asp-His catalytic triads, where Ser forms the reactive residue. Site-directed mutagenesis of residues comprising the predicted catalytic triad of Asp2 of S. gordonii had no effect upon GspB transport but did result in a marked change in the electrophoretic mobility of the protein. Lectin-binding studies and monosaccharide content analysis of this altered glycoform revealed an increase in glucosamine deposition. Random mutagenesis of the Asp2 region containing this catalytic domain also disrupted GspB transport. Collectively, our findings suggest that Asp2 is a bifunctional protein that is essential for both GspB transport and correct glycosylation. The catalytic domain may be responsible for controlling the glycosylation of GspB, while other surrounding regions are functionally required for glycoprotein transport. C1 [Sullam, Paul M.] San Francisco VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Sullam, PM (reprint author), San Francisco VA Med Ctr, San Francisco, CA USA. EM paul.sullam@ucsf.edu FU U.S. Department of Veteran Affairs; Northern California Institute for Research and Education; National Institutes of Health [R01 AI41513, R01 AI057433] FX This study was supported by the U.S. Department of Veteran Affairs, the Northern California Institute for Research and Education, and grants R01 AI41513 and R01 AI057433 from the National Institutes of Health. NR 47 TC 9 Z9 9 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD OCT PY 2012 VL 194 IS 20 BP 5564 EP 5575 DI 10.1128/JB.01000-12 PG 12 WC Microbiology SC Microbiology GA 016AV UT WOS:000309490600009 PM 22885294 ER PT J AU Lyman, GH Burstein, HJ Buzdar, AU D'Agostino, R Ellis, PA AF Lyman, Gary H. Burstein, Harold J. Buzdar, Aman U. D'Agostino, Ralph Ellis, Paul A. TI Making Genuine Progress Against Metastatic Breast Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID FREE SURVIVAL; ONCOLOGY PRODUCTS; PLUS DOCETAXEL; PHASE-III; BEVACIZUMAB; APPROVAL; AVASTIN; TIME C1 [Lyman, Gary H.] Duke Univ, Sch Med, Durham, NC 27706 USA. [Lyman, Gary H.] Duke Canc Inst, Durham, NC USA. [Burstein, Harold J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Buzdar, Aman U.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [D'Agostino, Ralph] Boston Univ, Boston, MA 02215 USA. [Ellis, Paul A.] Kings Coll London, London WC2R 2LS, England. [Ellis, Paul A.] Guys Hosp, London SE1 9RT, England. RP Lyman, GH (reprint author), Duke Univ, Sch Med, Durham, NC 27706 USA. NR 31 TC 8 Z9 8 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2012 VL 30 IS 28 BP 3448 EP 3451 DI 10.1200/JCO.2012.43.6931 PG 4 WC Oncology SC Oncology GA 016KS UT WOS:000309517700008 PM 22927527 ER PT J AU Asgharzadeh, S Salo, JA Ji, LY Oberthuer, A Fischer, M Berthold, F Hadjidaniel, M Liu, CWY Metelitsa, LS Pique-Regi, R Wakamatsu, P Villablanca, JG Kreissman, SG Matthay, KK Shimada, H London, WB Sposto, R Seeger, RC AF Asgharzadeh, Shahab Salo, Jill A. Ji, Lingyun Oberthuer, Andre Fischer, Matthias Berthold, Frank Hadjidaniel, Michael Liu, Cathy Wei-Yao Metelitsa, Leonid S. Pique-Regi, Roger Wakamatsu, Peter Villablanca, Judith G. Kreissman, Susan G. Matthay, Katherine K. Shimada, Hiroyuki London, Wendy B. Sposto, Richard Seeger, Robert C. TI Clinical Significance of Tumor-Associated Inflammatory Cells in Metastatic Neuroblastoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HIGH-RISK NEUROBLASTOMA; BONE-MARROW; 13-CIS-RETINOIC ACID; FAVORABLE PROGNOSIS; MYCN AMPLIFICATION; ONCOLOGY-GROUP; TASK-FORCE; CANCER; EXPRESSION; SURVIVAL AB Purpose Children diagnosed at age >= 18 months with metastatic MYCN-nonamplified neuroblastoma (NBL-NA) are at high risk for disease relapse, whereas those diagnosed at age < 18 months are nearly always cured. In this study, we investigated the hypothesis that expression of genes related to tumor-associated inflammatory cells correlates with the observed differences in survival by age at diagnosis and contributes to a prognostic signature. Methods Tumor-associated macrophages (TAMs) in localized and metastatic neuroblastomas (n = 71) were assessed by immunohistochemistry. Expression of 44 genes representing tumor and inflammatory cells was quantified in 133 metastatic NBL-NAs to assess age-dependent expression and to develop a logistic regression model to provide low-and high-risk scores for predicting progression-free survival (PFS). Tumors from high-risk patients enrolled onto two additional studies (n = 91) served as independent validation cohorts. Results Metastatic neuroblastomas had higher infiltration of TAMs than locoregional tumors, and metastatic tumors diagnosed in patients at age >= 18 months had higher expression of inflammation-related genes than those in patients diagnosed at age < 18 months. Expression of genes representing TAMs (CD33/CD16/IL6R/IL10/FCGR3) contributed to 25% of the accuracy of a novel 14-gene tumor classification score. PFS at 5 years for children diagnosed at age > 18 months with NBL-NA with a low-versus high-risk score was 47% versus 12%, 57% versus 8%, and 50% versus 20% in three independent clinical trials, respectively. Conclusion These data suggest that interactions between tumor and inflammatory cells may contribute to the clinical metastatic neuroblastoma phenotype, improve prognostication, and reveal novel therapeutic targets. J Clin Oncol 30:3525-3532. (C) 2012 by American Society of Clinical Oncology C1 [Asgharzadeh, Shahab; Salo, Jill A.; Hadjidaniel, Michael; Liu, Cathy Wei-Yao; Wakamatsu, Peter; Villablanca, Judith G.; Shimada, Hiroyuki; Sposto, Richard; Seeger, Robert C.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Asgharzadeh, Shahab; Salo, Jill A.; Hadjidaniel, Michael; Liu, Cathy Wei-Yao; Wakamatsu, Peter; Villablanca, Judith G.; Shimada, Hiroyuki; Sposto, Richard; Seeger, Robert C.] Saban Res Inst, Los Angeles, CA USA. [Asgharzadeh, Shahab; Ji, Lingyun; Villablanca, Judith G.; Shimada, Hiroyuki; Sposto, Richard; Seeger, Robert C.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Matthay, Katherine K.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Matthay, Katherine K.] Univ Calif San Francisco, Benioff Childrens Hosp, San Francisco, CA 94143 USA. [London, Wendy B.] Childrens Oncol Grp, Arcadia, CA USA. [London, Wendy B.] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Oberthuer, Andre; Fischer, Matthias; Berthold, Frank] Univ Cologne, Childrens Hosp, D-50931 Cologne, Germany. [Oberthuer, Andre; Fischer, Matthias; Berthold, Frank] Ctr Mol Med Cologne, Cologne, Germany. [Metelitsa, Leonid S.] Baylor Coll Med, Houston, TX 77030 USA. [Pique-Regi, Roger] Univ Chicago, Chicago, IL 60637 USA. [Kreissman, Susan G.] Duke Univ, Med Ctr, Durham, NC USA. RP Asgharzadeh, S (reprint author), 4650 Sunset Blvd,MS 57, Los Angeles, CA 90027 USA. EM sasgharzadeh@chla.usc.edu RI Pique-Regi, Roger/A-4110-2009 OI Pique-Regi, Roger/0000-0002-1262-2275 FU National Cancer Institute [2R01 CA60104-16]; Amgen; National Institute of Child Health and Human Development [K12-CA60104]; Alex's Lemonade Stand Foundation; St Baldrick's Foundation; Nautica Malibu Triathlon; Bogart Pediatric Cancer Research Program FX Supported by Grant No. 2R01 CA60104-16 from the National Cancer Institute (R. C. S.), a grant from Amgen (J.A.S.), Grant No. K12-CA60104 from the National Institute of Child Health and Human Development, grants from Alex's Lemonade Stand Foundation and St Baldrick's Foundation (S. A.), and grants from the Nautica Malibu Triathlon and Bogart Pediatric Cancer Research Program (S.A., R.C.S.). NR 54 TC 57 Z9 57 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2012 VL 30 IS 28 BP 3525 EP 3532 DI 10.1200/JCO.2011.40.9169 PG 8 WC Oncology SC Oncology GA 016KS UT WOS:000309517700018 PM 22927533 ER PT J AU Choe, KS Cowan, JE Chan, JM Carroll, PR D'Amico, AV Liauw, SL AF Choe, Kevin S. Cowan, Janet E. Chan, June M. Carroll, Peter R. D'Amico, Anthony V. Liauw, Stanley L. TI Aspirin Use and the Risk of Prostate Cancer Mortality in Men Treated With Prostatectomy or Radiotherapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PREVENT COLORECTAL ADENOMAS; DEEP-VEIN THROMBOSIS; RANDOMIZED-TRIAL; PULMONARY-EMBOLISM; MEDIATED APOPTOSIS; RADIATION-THERAPY; BONE METASTASIS; LARGE COHORT; INHIBITION AB Purpose Experimental evidence suggests that anticoagulants (ACs) may inhibit cancer growth and metastasis, but clinical data have been limited. We investigated whether use of ACs was associated with the risk of death from prostate cancer. Patients and Methods This study comprised 5,955 men in the Cancer of the Prostate Strategic Urologic Research Endeavor database with localized adenocarcinoma of the prostate treated with radical prostatectomy (RP) or radiotherapy (RT). Of them, 2,175 (37%) were receiving ACs (warfarin, clopidogrel, enoxaparin, and/or aspirin). The risk of prostate cancer-specific mortality (PCSM) was compared between the AC and non-AC groups. Results After a median follow-up of 70 months, risk of PCSM was significantly lower in the AC group compared with the non-AC group (3% v 8% at 10 years; P < .01). The risks of disease recurrence and bone metastasis were also significantly lower. In a subgroup analysis by clinical risk category, the reduction in PCSM was most prominent in patients with high-risk disease (4% v 19% at 10 years; P < .01). The benefit from AC was present across treatment modalities (RT or RP). Analysis by type of AC medication suggested that the PCSM reduction was primarily associated with aspirin. Multivariable analysis indicated that aspirin use was independently associated with a lower risk of PCSM (adjusted hazard ratio, 0.43; 95% CI, 0.21 to 0.87; P = .02). Conclusion AC therapy, particularly aspirin, was associated with a reduced risk of PCSM in men treated with RT or RP for prostate cancer. The association was most prominent in patients with high-risk disease. J Clin Oncol 30:3540-3544. (C) 2012 by American Society of Clinical Oncology C1 [Choe, Kevin S.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Cowan, Janet E.; Chan, June M.; Carroll, Peter R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [D'Amico, Anthony V.] Brigham & Womens Hosp, Boston, MA 02115 USA. [D'Amico, Anthony V.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Liauw, Stanley L.] Univ Chicago, Chicago, IL 60637 USA. RP Liauw, SL (reprint author), Univ Chicago Hosp, Dept Radiat & Cellular Oncol, 5758 S Maryland Ave,MC 9006, Chicago, IL 60637 USA. EM sliauw@radonc.uchicago.edu FU National Institutes of Health/National Cancer Institute [5RC1CA146596]; Agency for Healthcare Research and Quality [1U01CA88160] FX The Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) is supported by an unrestricted educational gift from Abbott Laboratories (Chicago, IL), by the National Institutes of Health/National Cancer Institute (Grant No. 5RC1CA146596), and by the Agency for Healthcare Research and Quality (Grant No. 1U01CA88160). NR 35 TC 42 Z9 42 U1 1 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2012 VL 30 IS 28 BP 3540 EP 3544 DI 10.1200/JCO.2011.41.0308 PG 5 WC Oncology SC Oncology GA 016KS UT WOS:000309517700020 PM 22927523 ER PT J AU Xu, YP Simon, JE Ferruzzi, MG Ho, L Pasinetti, GM Wu, QL AF Xu, Yanping Simon, James E. Ferruzzi, Mario G. Ho, Lap Pasinetti, Giulio Maria Wu, Qingli TI Quantification of anthocyanidins in the grapes and grape juice products with acid assisted hydrolysis using LC/MS SO JOURNAL OF FUNCTIONAL FOODS LA English DT Article DE Grape; LC-MS; Polyphenols; Anthocyanins; Anthocyanidins; Acidic hydrolysis ID ANTIOXIDANT ACTIVITY; RED WINES; CAPACITY; IDENTIFICATION; STRESS AB A simple and precise acid-assisted hydrolysis method was established for the quantification of anthocyanidins in 15 grape juice samples, four grape berries and four grape skins using LC/MS. Under optimized conditions, five major anthocyanidins including delphinidin, cyanidin, petunidin, peonidin and malvidin in the hydrolyzed grape extracts were successfully separated within 25 mm and quantified individually. The results revealed that the total concentration of anthocyanidins was not symmetrically distributed in the different grape juice products. While quantitative distribution of anthocyanidins in grape berries and skins are quite similar, anthocyanidin concentration in grape skins was found to be four to eight times higher than their corresponding berries. The precision of this method was validated by recovery percentages of five anthocyanidins, ranging from 98.59% to 103.20% with the relative standard deviation (RSD) less than 5.03%. This quantitative method provides a rapid and accurate tool to quantitatively study individual anthocyanidins in grapes or grape juice samples for quality control and to facilitate the evaluation and comparison of new commercial grapes or grape juices products in the market. (c) 2012 Elsevier Ltd. All rights reserved. C1 [Xu, Yanping; Simon, James E.; Wu, Qingli] Rutgers State Univ, Dept Plant Biol & Pathol, New Use Agr & Nat Plant Prod Program, New Brunswick, NJ 08901 USA. [Xu, Yanping; Simon, James E.; Wu, Qingli] Rutgers State Univ, Ernest Mario Sch Pharm, Dept Med Chem, Piscataway, NJ 08854 USA. [Ferruzzi, Mario G.] Purdue Univ, Dept Food Sci, W Lafayette, IN 47907 USA. [Ho, Lap; Pasinetti, Giulio Maria] Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. [Pasinetti, Giulio Maria] James J Peters Vet Affairs Med Ctr, GRECC, Bronx, NY 10468 USA. RP Wu, QL (reprint author), Rutgers State Univ, Dept Plant Biol & Pathol, New Use Agr & Nat Plant Prod Program, 59 Dudley Rd, New Brunswick, NJ 08901 USA. EM qlwu@aesop.rutgers.edu FU New Use Agriculture and Natural Plant Products Program; NIH [1 PO1 AT004511-01] FX This work was supported by the New Use Agriculture and Natural Plant Products Program and was conducted as part of the Core B Research Program in CERC with funds provided by NIH Award 1 PO1 AT004511-01. Many thanks to Stephen T. Talcott, Texas A&M University for isolating juice polyphenolic preparations; JoLynne Wrightman, Welch's Inc., for providing the Concord Grape Juice and their helpful discussions. NR 22 TC 11 Z9 12 U1 3 U2 54 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1756-4646 J9 J FUNCT FOODS JI J. Funct. Food. PD OCT PY 2012 VL 4 IS 4 BP 710 EP 717 DI 10.1016/j.jff.2012.04.010 PG 8 WC Food Science & Technology SC Food Science & Technology GA 017CZ UT WOS:000309569000002 ER PT J AU Wright, DE Hunt, DP AF Wright, Douglas E. Hunt, Daniel P. TI Core competency review: Aortic stenosis and noncardiac surgery SO JOURNAL OF HOSPITAL MEDICINE LA English DT Review ID INTRAOPERATIVE TRANSESOPHAGEAL ECHOCARDIOGRAPHY; BALLOON VALVULOPLASTY; CARDIAC RISK; PRACTICE GUIDELINES; VALVE STENOSIS; PREDICTION; MANAGEMENT; COMPLICATIONS; PATIENT; ADULTS AB Aortic stenosis (AS) poses a risk of adverse cardiac events for patients undergoing surgical procedures. Perioperative mortality for patients with severe AS is as high as 14%. This review examines the accuracy of the history and physical examination in detecting AS and, subsequently, in assessing severity. The utility of echocardiography is addressed, and the relevant pathophysiology of AS is summarized. We also summarize what is known about perioperative risk for patients with AS. Journal of Hospital Medicine 2012;. (c) 2012 Society of Hospital Medicine C1 [Wright, Douglas E.; Hunt, Daniel P.] Massachusetts Gen Hosp, Inpatient Clinician Educ Serv, Boston, MA 02114 USA. [Wright, Douglas E.; Hunt, Daniel P.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Hunt, DP (reprint author), Massachusetts Gen Hosp, Inpatient Clinician Educ Serv, 50 Staniford St,Suite 503B, Boston, MA 02114 USA. EM dphunt@partners.org NR 34 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD OCT PY 2012 VL 7 IS 8 BP 655 EP 660 DI 10.1002/jhm.1952 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 015NQ UT WOS:000309453600012 PM 22733448 ER PT J AU Joshi, A Ringman, JM Lee, AS Juarez, KO Mendez, MF AF Joshi, Aditi Ringman, John M. Lee, Albert S. Juarez, Kevin O. Mendez, Mario F. TI Comparison of clinical characteristics between familial and non-familial early onset Alzheimer's disease SO JOURNAL OF NEUROLOGY LA English DT Article DE Dementia; Early onset Alzheimer's disease; Familial Alzheimer's disease; PSEN1 gene ID PRESENILIN-1 MUTATION CARRIERS; POSTERIOR CORTICAL ATROPHY; AMYLOID DEPOSITION; DIAGNOSIS; PATHOLOGY; SEIZURES; FEATURES; PLAQUES; VARIANT; RISK AB Although familial Alzheimer's disease (FAD) is an early onset AD (EAD), most patients with EAD do not have a familial disorder. Recent guidelines recommend testing for genes causing FAD only in those EAD patients with two first-degree relatives. However, some patients with FAD may lack a known family history or other indications for suspecting FAD but might nonetheless be carriers of FAD mutations. The study was aimed to identify clinical features that distinguish FAD from non-familial EAD (NF-EAD). A retrospective review of a university-based cohort of 32 FAD patients with PSEN1-related AD and 81 with NF-EAD was conducted. The PSEN1 patients, compared to the NF-EAD patients, had an earlier age of disease onset (41.8 +/- A 5.2 vs. 55.9 +/- A 4.8 years) and, at initial assessment, a longer disease duration (5.1 +/- A 3.4 vs. 3.3 +/- A 2.6 years) and lower MMSE scores (10.74 +/- A 8.0 vs. 20.95 +/- A 5.8). Patients with NF-EAD were more likely to present with non-memory deficits, particularly visuospatial symptoms, than were FAD patients. When age, disease duration, and MMSE scores were controlled in a logistical regression model, FAD patients were more likely to have significant headaches, myoclonus, gait abnormality, and pseudobulbar affect than those with NF-EAD. In addition to a much younger age of onset, FAD patients with PSEN1 mutations differed from those with NF-EAD by a history of headaches and pseudobulbar affect, as well as myoclonus and gait abnormality on examination. These may represent differences in pathophysiology between FAD and NF-EAD and in some contexts such findings should lead to genetic counseling and appropriate recommendations for genetic testing for FAD. C1 [Joshi, Aditi; Juarez, Kevin O.; Mendez, Mario F.] VA Greater Los Angeles Healthcare Ctr, Neurol Sect, Neurobehav Unit 691 116AF, Los Angeles, CA 90073 USA. [Joshi, Aditi; Ringman, John M.; Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Ringman, John M.; Mendez, Mario F.] Univ Calif Los Angeles, Mary S Easton Ctr Alzheimers Dis Res, Los Angeles, CA USA. [Lee, Albert S.; Mendez, Mario F.] Western Univ Hlth Sci, Pomona, CA USA. RP Joshi, A (reprint author), VA Greater Los Angeles Healthcare Ctr, Neurol Sect, Neurobehav Unit 691 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM aditijoshi@mednet.ucla.edu FU VA Merit Review; Alzheimer's Disease Research Center [NIA P50 AG-16570]; PHS [K08 AG-22228]; California DHS [04-35522]; California Alzheimer's Disease Center [09-11408]; Easton Consortium for Alzheimer's Disease Drug Discovery and Biomarkers; [R01AG034499-03] FX This work was supported by grant #R01AG034499-03 and a VA Merit Review (A. Joshi, A. Lee, K. O. Juarez, and M. F. Mendez), Alzheimer's Disease Research Center Grant NIA P50 AG-16570 ( M. F. Mendez, J.M. Ringman). Dr. Ringman receives additional support from PHS K08 AG-22228, California DHS #04-35522, California Alzheimer's Disease Center Grant 09-11408, and the Easton Consortium for Alzheimer's Disease Drug Discovery and Biomarkers. NR 39 TC 13 Z9 14 U1 2 U2 21 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD OCT PY 2012 VL 259 IS 10 BP 2182 EP 2188 DI 10.1007/s00415-012-6481-y PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 017BD UT WOS:000309562800022 PM 22460587 ER PT J AU Beadell, NC Thompson, EM Delashaw, JB Cetas, JS AF Beadell, Noah C. Thompson, Eric M. Delashaw, Johnny B. Cetas, Justin S. TI The deleterious effects of methamphetamine use on initial presentation and clinical outcomes in aneurysmal subarachnoid hemorrhage SO JOURNAL OF NEUROSURGERY LA English DT Article DE methamphetamine; subarachnoid hemorrhage; aneurysm; outcome; vascular disorders; vasospasm ID INTRACEREBRAL HEMORRHAGE; YOUNG-ADULTS; CEREBRAL VASOSPASM; ORAL AMPHETAMINE; ISCHEMIC-STROKE; ABUSE; COCAINE; COMPLICATIONS; INHALATION; ANGIITIS AB Object. The objective of this study was to retrospectively look at methamphetamine (MA) use in patients with aneurysmal subarachnoid hemorrhage (SAH) to determine if MA use affects clinical presentation and outcomes after aneurysmal SAH. Methods. A retrospective review of patients admitted to the Oregon Health & Science University neurosurgical service with aneurysmal SAH during the past 6 years was undertaken. Variables analyzed included MA use, age, sex, cigarette use, Hunt and Hess grade, Fisher grade, admission blood pressure, aneurysm characteristics, occurrence of vasospasm, hospital length of stay (LOS), cerebral infarction, aneurysm treatment, and Glasgow Outcome Scale (GOS) score. Data differences between MA users and nonusers were statistically analyzed using multivariate logistic regression analysis. A separate comparison with randomly selected age-matched nonuser controls was also performed. Results. Twenty-eight (7%) of 374 patients with aneurysmal SAH were identified as MA users. Methamphetamine users were younger than nonusers (45.2 vs 55.9 years, respectively; p < 0.001). Despite a younger age, MA users had significantly higher Hunt and Hess grades than nonusers (3.0 vs 2.5, respectively; p < 0.020) and age-matched controls (3.0 vs 2.0, respectively; p < 0.001). Earliest available mean arterial pressure was significantly higher in MA users (122.1 vs 109.7, respectively; p = 0.005) than all nonusers but not age-matched controls. Methamphetamine users had significantly higher vasospasm rates than nonusers (92.9% vs 71.1%, respectively; p = 0.008) but similar rates as age-matched controls (92.9% vs 89.3%, respectively; p = 0.500). Glasgow Outcome Scale score did not differ significantly between users and nonusers (3 vs 4, respectively; p = 0.170), but users had significantly lower GOS scores than age-matched controls (3 vs 5, respectively; p < 0.001). There was no statistically significant difference in the LOS between users and nonusers (18 days vs 16 days, respectively; p = 0.431) or users and age-matched controls (18 days vs 14 days, respectively; p = 0.250). In the multivariate analysis, MA use (OR 3.777, p = 0.018), age (p < 0.001), Fisher grade (p = 0.011), Hunt and Hess grade (p < 0.001), and cerebral infarction (p < 0.001) were predictors of poor GOS score. The only predictor of vasospasm was age (p < 0.001), although a strong predictive trend in MA use (p = 0.149) was found. Predictors of a hospital LOS > 15 days included age (p = 0.002), Fisher grade (p = 0.002), Hunt and Hess grade (p < 0.001). and cerebral infarction (p < 0.001). Predictors of cerebral infarction include male sex (p = 0.022) and Hunt and Hess grade (p = 0.006), with vasospasm demonstrating a strong trend (p = 0.056). Conclusions. A history of MA use may predict poorer outcomes in patients who present with aneurysmal SAH. Methamphetamine users have significantly worse presentations and outcomes when compared with age-matched controls. (http://thejns.org/doi/abs/10.3171/2012.7.JNS12396) C1 [Thompson, Eric M.; Delashaw, Johnny B.; Cetas, Justin S.] Oregon Hlth & Sci Univ, Dept Neurol Surg, Portland, OR 97239 USA. [Beadell, Noah C.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. [Cetas, Justin S.] Portland VA Med Ctr, Portland, OR USA. RP Cetas, JS (reprint author), Oregon Hlth & Sci Univ, Dept Neurol Surg, Mail Code L472,3303 Bond Ave SW, Portland, OR 97239 USA. EM cetasj@ohsu.edu NR 38 TC 4 Z9 4 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD OCT PY 2012 VL 117 IS 4 BP 781 EP 786 DI 10.3171/2012.7.JNS12396 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 015YZ UT WOS:000309485600033 PM 22920957 ER PT J AU Cheng, G Alavi, A AF Cheng, Gang Alavi, Abass TI The Value of F-18-FDG PET/CT in the Assessment of Cardiac Malignancy Remains to Be Defined SO JOURNAL OF NUCLEAR MEDICINE LA English DT Letter ID LOW-CARBOHYDRATE-DIET; HIGH-FAT; MYOCARDIAL UPTAKE; FDG UPTAKE; SUPPRESSION; DIAGNOSIS; HEART C1 [Cheng, Gang] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Cheng, G (reprint author), Philadelphia VA Med Ctr, 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM gangcheng99@yahoo.com NR 8 TC 1 Z9 1 U1 0 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD OCT PY 2012 VL 53 IS 10 BP 1657 EP 1657 DI 10.2967/jnumed.112.109611 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 015FS UT WOS:000309432400027 PM 22915158 ER PT J AU Angel, TE Jacobs, JM Smith, RP Pasternack, MS Elias, S Gritsenko, MA Shukla, A Gilmore, EC McCarthy, C Camp, DG Smith, RD Warren, HS AF Angel, Thomas E. Jacobs, Jon M. Smith, Robert P. Pasternack, Mark S. Elias, Susan Gritsenko, Marina A. Shukla, Anil Gilmore, Edward C. McCarthy, Carol Camp, David G., II Smith, Richard D. Warren, H. Shaw TI Cerebrospinal Fluid Proteome of Patients with Acute Lyme Disease SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE proteomics; mass spectrometry; Lyme disease; cerebrospinal fluid; Lyme neuroborreliosis ID BORRELIA-BURGDORFERI; NEUROBORRELIOSIS; PATHOGENESIS; INFLAMMATION; DEGRADATION; BIOMARKERS; INFECTION; PROTEINS; CD44; MASS AB During acute Lyme disease, bacteria can disseminate to the central nervous system (CNS), leading to the development of meningitis and other neurologic symptoms. Here we have analyzed pooled cerebrospinal fluid (CSF) allowing a deep view into the proteome for patients diagnosed with early disseminated Lyme disease and CSF inflammation. Additionally, we analyzed individual patient samples and quantified differences in protein abundance employing label-free quantitative mass spectrometry-based methods. We identified 108 proteins that differ significantly in abundance in patients with acute Lyme disease from controls. Comparison between infected patients and control subjects revealed differences in proteins in the CSF associated with cell death localized to brain synapses and others that likely originate from brain parenchyma. C1 [Angel, Thomas E.; Jacobs, Jon M.; Gritsenko, Marina A.; Shukla, Anil; Camp, David G., II; Smith, Richard D.] Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA. [Smith, Robert P.; Elias, Susan; McCarthy, Carol] Maine Med Ctr, Res Inst, Vector Borne Dis Lab, Portland, ME 04106 USA. [Pasternack, Mark S.; Warren, H. Shaw] Massachusetts Gen Hosp, Dept Pediat, Infect Dis Unit, Boston, MA 02114 USA. [Pasternack, Mark S.; Warren, H. Shaw] Massachusetts Gen Hosp, Dept Med, Infect Dis Unit, Boston, MA 02114 USA. [Gilmore, Edward C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Smith, RD (reprint author), Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA. EM RDS@pnnl.gov RI Smith, Richard/J-3664-2012 OI Smith, Richard/0000-0002-2381-2349 FU National Center for Research Resources [5P41RR018522-10]; National Institute of General Medical Sciences from the National Institutes of Health [8 P41 GM103493-10]; NIH [AI059010]; Shriners Hospital for Crippled Children [87200]; U.S. Department of Energy [DE-AC05-76RLO 1830] FX This research was supported by grants from the National Center for Research Resources (5P41RR018522-10) and the National Institute of General Medical Sciences (8 P41 GM103493-10) from the National Institutes of Health to R.D.S.), and by NIH grant AI059010 and grant 87200 from the Shriners Hospital for Crippled Children to H.S.W. The analytical work was performed in the Environmental Molecular Sciences Laboratory, U.S. Department of Energy Office of Biological and Environmental Research national scientific user facility located at Pacific Northwest National Laboratory in Richland, Washington. Pacific Northwest National Laboratory is operated by Battelle for the U.S. Department of Energy under Contract No. DE-AC05-76RLO 1830. Additional support for clinical sample acquisition was provided by the Maine Medical Center Neuroscience Institute. The authors acknowledge the assistance of Drs. Mark Eggena and Cheryl Liechty in provision of Penobscot Bay Medical Center, Rockland Maine in the provision of cerebrospinal fluid samples. NR 45 TC 4 Z9 4 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD OCT PY 2012 VL 11 IS 10 BP 4814 EP 4822 DI 10.1021/pr300577p PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 015JA UT WOS:000309441000005 PM 22900834 ER PT J AU Urbanoski, KA Kelly, JF Hoeppner, BB Slaymaker, V AF Urbanoski, Karen A. Kelly, John F. Hoeppner, Bettina B. Slaymaker, Valerie TI The role of therapeutic alliance in substance use disorder treatment for young adults SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE Young adults; Substance use treatment; Therapeutic alliance; Motivation ID ALCOHOL-USE DISORDER; ABUSE TREATMENT; WORKING ALLIANCE; SINGLE-ITEM; TREATMENT OUTCOMES; SELF-EFFICACY; INVENTORY; MISUSE; VALIDATION; CLIENTS AB The therapeutic alliance is deemed to be integral to psychotherapeutic interventions, yet little is known about the nature of its role in treatment for substance use disorders (SUD), especially among young people. We investigated baseline predictors of the therapeutic alliance measured midtreatment and tested whether the alliance influenced during-treatment changes in key process variables (psychological distress, motivation, self-efficacy, coping skills, and commitment to Alcoholics Anonymous/Narcotics Anonymous [AA/NA]) independent of these baseline influences. Young adults in residential treatment (N = 303; age 18-24 years) were assessed at intake, midtreatment, and discharge. Older age and higher baseline levels of motivation, self-efficacy, coping skills, and commitment to AA/NA predicted a stronger alliance. Independent of these influences, participants who developed a stronger alliance achieved greater reductions in distress during treatment. Findings clarify a role for alliance in promoting during-treatment changes through reducing distress. (C) 2012 Elsevier Inc. All rights reserved. C1 [Urbanoski, Karen A.; Kelly, John F.; Hoeppner, Bettina B.] Massachusetts Gen Hosp, Ctr Addict Med, Boston, MA 02114 USA. [Urbanoski, Karen A.; Kelly, John F.; Hoeppner, Bettina B.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Slaymaker, Valerie] Hazelden Fdn, Butler Ctr Res, Ctr City, MN 55012 USA. RP Kelly, JF (reprint author), Massachusetts Gen Hosp, Ctr Addict Med, Boston, MA 02114 USA. EM jkelly11@partners.org OI Urbanoski, Karen/0000-0001-7287-7176 FU NIAAA NIH HHS [R21 AA018185-01A2, R21 AA018185-02, R21AA018185, R21 AA018185]; NIDA NIH HHS [L30 DA025511, K01 DA027097, K01DA027097] NR 48 TC 11 Z9 11 U1 4 U2 29 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD OCT PY 2012 VL 43 IS 3 BP 344 EP 351 DI 10.1016/j.jsat.2011.12.013 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 017DS UT WOS:000309570900010 PM 22285833 ER PT J AU Eagan, MJ Zuk, PA Zhao, KW Bluth, BE Brinkmann, EJ Wu, BM McAllister, DR AF Eagan, Michael J. Zuk, Patricia A. Zhao, Ke-Wei Bluth, Benjamin E. Brinkmann, Elyse J. Wu, Benjamin M. McAllister, David R. TI The suitability of human adipose-derived stem cells for the engineering of ligament tissue SO JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE LA English DT Article DE ASCs; adipose-derived stem cells; ligament engineering; collagen type 1; tissue engineering; adult stem cells ID ANTERIOR CRUCIATE LIGAMENT; MEDIAL COLLATERAL LIGAMENT; MARROW STROMAL CELLS; GROWTH-FACTORS; TENASCIN-C; IN-VITRO; MATRIX SYNTHESIS; PATELLAR TENDON; SILK SCAFFOLD; RABBIT MODEL AB Rupture of the anterior cruciate ligament (ACL) is the one of the most common sports-related injuries. With its poor healing capacity, surgical reconstruction using either autografts or allografts is currently required to restore function. However, serious complications are associated with graft reconstructions and the number of such reconstructions has steadily risen over the years, necessitating the search for an alternative approach to ACL repair. Such an approach may likely be tissue engineering. Recent engineering approaches using ligament-derived fibroblasts have been promising, but the slow growth rate of such fibroblasts in vitro may limit their practical application. More promising results are being achieved using bone marrow mesenchymal stem cells (MSCs). The adipose-derived stem cell (ASC) is often proposed as an alternative choice to the MSC and, as such, may be a suitable stem cell for ligament engineering. However, the use of ASCs in ligament engineering still remains relatively unexplored. Therefore, in this study, the potential use of human ASCs in ligament tissue engineering was initially explored by examining their ability to express several ligament markers under growth factor treatment. ASC populations treated for up to 4?weeks with TGF beta 1 or IGF1 did not show any significant and consistent upregulation in the expression of collagen types 1 and 3, tenascin C and scleraxis. While treatment with EGF or bFGF resulted in increased tenascin C expression, increased expression of collagens 1 and 3 were never observed. Therefore, simple in vitro treatment of human ASC populations with growth factors may not stimulate their ligament differentiative potential. Copyright (c) 2011 John Wiley & Sons, Ltd. C1 [Zhao, Ke-Wei; McAllister, David R.] VA Greater Los Angeles Healthcare Syst, Orthoped Tissue Engn Lab, W Los Angeles Healthcare Ctr, Los Angeles, CA 90073 USA. [Eagan, Michael J.; McAllister, David R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Orthoped Surg, Ctr Hlth Sci, Los Angeles, CA 90095 USA. [Zuk, Patricia A.; Bluth, Benjamin E.] Univ Calif Los Angeles, David Geffen Sch Med, Div Plast Surg, Dept Surg,Ctr Hlth Sci, Los Angeles, CA 90095 USA. [Brinkmann, Elyse J.; Wu, Benjamin M.] Univ Calif Los Angeles, Dept Biomed Engn, Henry Samueli Sch Engn & Appl Sci, Los Angeles, CA 90095 USA. RP McAllister, DR (reprint author), VA Greater Los Angeles Healthcare Syst, Orthoped Tissue Engn Lab, W Los Angeles Healthcare Ctr, Room E3-201,Bldg 304,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM pzuk@mednet.ucla.edu FU VA Rehabilitation RRD grant FX This study was supported by a VA Rehabilitation RR&D grant. NR 63 TC 10 Z9 10 U1 4 U2 29 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1932-6254 J9 J TISSUE ENG REGEN M JI J. Tissue Eng. Regen. Med. PD OCT PY 2012 VL 6 IS 9 BP 702 EP 709 DI 10.1002/term.474 PG 8 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Engineering, Biomedical SC Cell Biology; Biotechnology & Applied Microbiology; Engineering GA 015QH UT WOS:000309460500004 PM 21953999 ER PT J AU Dawson, SL AF Dawson, Steven L. TI Evaluation of the Orcamp Hybrid High-fidelity Environment for Simulation Training SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Imaging, Boston, MA 02114 USA. RP Dawson, SL (reprint author), Massachusetts Gen Hosp, Dept Imaging, 55 Fruit St, Boston, MA 02114 USA. EM mghrad79@gmail.com NR 7 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD OCT PY 2012 VL 23 IS 10 BP 1367 EP 1368 DI 10.1016/j.jvir.2012.07.016 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 015YT UT WOS:000309484900023 PM 22999757 ER PT J AU Nolan, BW De Martino, RR Goodney, PP Schanzer, A Stone, DH Butzel, D Kwolek, CJ Cronenwett, JL AF Nolan, Brian W. De Martino, Randall R. Goodney, Philip P. Schanzer, Andres Stone, David H. Butzel, David Kwolek, Christopher J. Cronenwett, Jack L. CA Vasc Study Grp New England TI Comparison of carotid endarterectomy and stenting in real world practice using a regional quality improvement registry SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID NORTHERN NEW-ENGLAND; VASCULAR-SURGERY; CARDIAC TROPONIN; RISK-FACTORS; STENOSIS; DEATH; STROKE; MORTALITY; EVENTS; TRIAL AB Objective: Carotid artery stenting (CAS) vs endarterectomy (CEA) remains controversial and has been the topic of recent randomized controlled trials. The purpose of this study was to compare the practice and outcomes of CAS and CEA in a real world setting. Methods: This is a retrospective analysis of 7649 CEA and 430 CAS performed at 17 centers from 2003 to 2010 within the Vascular Study Group of New England (VSGNE). The primary outcome measures were (1) any in-hospital stroke or death and (2) any stroke, death, or myocardial infarction (MI). Patients undergoing CEA in conjunction with cardiac surgery were excluded. Multivariate logistic regression was performed to identify predictors of stroke or death in patients undergoing CAS. Results: CEA was performed in 17 centers by 111 surgeons, while CAS was performed in 6 centers by 30 surgeons and 8 interventionalists. Patient characteristics varied by procedure. Patients undergoing CAS had a higher prevalence of coronary artery disease, congestive heart failure, diabetes, and prior ipsilateral CEA. Embolic protection was used in 97% of CAS. Shunts were used in 48% and patches in 86% of CEA. The overall in-hospital stroke or death rate was higher among patients undergoing CAS (2.3% vs 1.1%; P = .03). Overall stroke, death, or MI (2.8% CAS vs 2.1% CEA; P = .32) were not different. Asymptomatic patients had similar rates of stroke or death (CAS 0.73% vs CEA 0.89%; P = .78) and stroke, death, or MI (CAS 1.1% vs CEA 1.8%; P = .40). Symptomatic patients undergoing CAS had higher rates of stroke or death (5.1% vs 1.6%; P = .001), and stroke, death, or MI (5.8% vs 2.7%; P = .02). By multivariate analysis, major stroke (odds ratio, 4.5; 95% confidence interval [CI], 1.9-10.8), minor stroke (2.7; CI, 1.5-4.8), prior ipsilateral CEA (3.2, CI, 1.7-6.1), age > 80 (2.1; CI, 1.3-3.4), hypertension (2.6; CI, 1.0-6.3), and a history of chronic obstructive pulmonary disease (1.6; CI, 1.0-2.4) were predictors of stroke or death in patients undergoing carotid revascularization. Conclusions: In our regional vascular surgical practices, the overall outcomes of CAS and CEA are similar for asymptomatic patients. However, symptomatic patients treated with CAS are at a higher risk for stroke or death. (J Vasc Surg 2012;56:990-6.) C1 [Nolan, Brian W.; De Martino, Randall R.; Goodney, Philip P.; Stone, David H.; Cronenwett, Jack L.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Schanzer, Andres] Univ Massachusetts, Mem Med Ctr, Worcester, MA 01605 USA. [Butzel, David] Maine Med Ctr, Portland, ME 04102 USA. [Kwolek, Christopher J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Nolan, BW (reprint author), Vasc Surg Sect 3V, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM brian.nolan@hitchcock.org FU NHLBI NIH HHS [K08 HL105676]; NIMHD NIH HHS [L32 MD006323] NR 20 TC 14 Z9 15 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD OCT PY 2012 VL 56 IS 4 BP 990 EP 996 DI 10.1016/j.jvs.2012.03.009 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 016IV UT WOS:000309512300014 PM 22579135 ER PT J AU Cambria, RP AF Cambria, Richard P. TI Commentary regarding "Lower-extremity endovascular interventions for Medicare beneficiaries: Comparative effectiveness as a function of provider specialty" by Zafar et al. J Vasc Interv Radiol 2012;23:3-9 SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID TRENDS C1 Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. RP Cambria, RP (reprint author), Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. NR 7 TC 1 Z9 1 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD OCT PY 2012 VL 56 IS 4 BP 1105 EP 1106 DI 10.1016/j.jvs.2012.08.046 PG 2 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 016IV UT WOS:000309512300031 PM 23026422 ER PT J AU Kakarala, K Emerick, KS Lin, DT Rocco, JW Deschler, DG AF Kakarala, Kiran Emerick, Kevin S. Lin, Derrick T. Rocco, James W. Deschler, Daniel G. TI Free flap reconstruction in 1999 and 2009: Changing case characteristics and outcomes SO LARYNGOSCOPE LA English DT Article DE Microvascular; free flap; head and neck; reconstruction ID FREE-TISSUE TRANSFER; NECK RECONSTRUCTION; HEAD; COMPLICATIONS; DEFECTS AB Objectives/Hypothesis: To compare free flap reconstructive cases from 1999 and 2009 with respect to patient characteristics, surgical characteristics, outcomes, and complications; and to discuss the evolution in free flap reconstruction at a single institution during this time period. Study Design: Retrospective cohort comparison. Methods: Free flap reconstruction cases from 1999 and 2009 were collected into two cohorts. Retrospective chart review was performed to extract patient characteristics, surgical characteristics, and outcomes. Cohorts were compared with respect to extracted data with statistical significance set at P < .05. Results: There were 39 free flap reconstructions performed in 1999 and 81 performed in 2009. Patients in the 2009 cohort had higher American Society of Anesthesiologists scores and incidence of cardiovascular disease (P = .009 and .0045, respectively). Median operative time decreased from 12 hours in 1999 to 9 hours in 2009 (P < .0001). Median length of stay decreased from 14 to 9 days (P = .0006). The rate of perioperative return to the operating room to manage complications decreased from 30% to 17% (P = .103). There were five unsalvaged flap failures in 1999 (12.8%) compared to two failures in 2009 (2.5%) (P = .036). Conclusions: Patients undergoing free flap reconstruction are increasingly older and have more medical comorbidities. Despite these challenges, increased efficiency and teamwork stemming from accumulated institutional experience have led to decreased operative times, length of stay, and complication rates and increased overall success rates. C1 [Kakarala, Kiran; Emerick, Kevin S.; Lin, Derrick T.; Rocco, James W.; Deschler, Daniel G.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Head & Neck Surg, Boston, MA 02114 USA. [Kakarala, Kiran; Emerick, Kevin S.; Lin, Derrick T.; Rocco, James W.; Deschler, Daniel G.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Deschler, DG (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM daniel_deschler@meei.harvard.edu OI Kakarala, Kiran/0000-0002-1003-8024 NR 10 TC 9 Z9 9 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 2012 VL 122 IS 10 BP 2160 EP 2163 DI 10.1002/lary.23457 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 009XZ UT WOS:000309060200009 PM 22674647 ER PT J AU Berkowitz, LR AF Berkowitz, Lori R. TI Focused teaching in menopause: the time is now SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID WOMENS HEALTH C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Berkowitz, LR (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 9 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD OCT PY 2012 VL 19 IS 10 BP 1072 EP 1073 DI 10.1097/gme.0b013e31826cd9a3 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 016ZQ UT WOS:000309558800006 PM 23014138 ER PT J AU Foo, JP Mantzoros, CS AF Foo, Joo-Pin Mantzoros, Christos S. TI Leptin in congenital or HIV-associated lipodystrophy and metabolic syndrome: A need for more mechanistic studies and large, randomized, placebo-controlled trials SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Editorial Material ID ACTIVE ANTIRETROVIRAL THERAPY; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; REVERSES INSULIN-RESISTANCE; VIRUS-INFECTED PATIENTS; RECOMBINANT HUMAN LEPTIN; HORMONE-RELEASING FACTOR; MYOCARDIAL-INFARCTION; PROTEASE-INHIBITOR; DOUBLE-BLIND; REPLACEMENT THERAPY C1 [Foo, Joo-Pin; Mantzoros, Christos S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab,Dept Internal Med, Boston, MA 02215 USA. [Mantzoros, Christos S.] Harvard Univ, Dept Internal Med, Sch Med, VA Boston Healthcare Syst,Sect Endocrinol, Boston, MA USA. RP Foo, JP (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Endocrinol Diabet & Metab,Dept Internal Med, Boston, MA 02215 USA. EM cmantzor@bidmc.harvard.edu NR 65 TC 10 Z9 10 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD OCT PY 2012 VL 61 IS 10 BP 1331 EP 1336 DI 10.1016/j.metabol.2012.04.013 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 017YA UT WOS:000309625900001 PM 22592129 ER PT J AU Meyer, CA Tang, QZ Liu, XS AF Meyer, Clifford A. Tang, Qianzi Liu, X. Shirley TI Minireview: Applications of Next-Generation Sequencing on Studies of Nuclear Receptor Regulation and Function SO MOLECULAR ENDOCRINOLOGY LA English DT Review ID DNA METHYLATION; GENE-EXPRESSION; TRANSCRIPTION FACTORS; HUMAN GENOME; CHROMOSOME CONFORMATION; RNA-SEQ; CHROMATIN ACCESSIBILITY; PROSTATE-CANCER; THYROID-HORMONE; RETINOIC ACID AB Next-generation sequencing technologies have expanded the experimental possibilities for studying the genome-wide regulation of transcription by nuclear receptors, their collaborating transcription factors, and coregulators. These technologies allow investigators to obtain abundance and DNA sequence information in a single experiment. In this review, we highlight proven and potential uses of next-generation sequencing in the study of gene regulation by nuclear receptors. We also provide suggestions on how to effectively leverage this technology in a collaborative environment. (Molecular Endocrinology 26: 1651-1659, 2012) C1 [Meyer, Clifford A.; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Tang, Qianzi] Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R China. RP Liu, XS (reprint author), Harvard Univ, Sch Publ Hlth Biostat & Computat Biol, Dana Farber Canc Inst, 450 Brookline St, Boston, MA 02215 USA. EM xsliu@jimmy.harvard.edu FU United States National Institutes of Health [HG4069]; National Natural Science Foundation of China [31028011] FX This work was supported by the United States National Institutes of Health (HG4069) and the National Natural Science Foundation of China (31028011). NR 85 TC 6 Z9 6 U1 0 U2 8 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD OCT PY 2012 VL 26 IS 10 BP 1651 EP 1659 DI 10.1210/me.2012-1150 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 016HW UT WOS:000309509500003 PM 22930692 ER PT J AU Holt, JR Vandenberghe, LH AF Holt, Jeffrey R. Vandenberghe, Luk H. TI Gene Therapy for Deaf Mice Goes Viral SO MOLECULAR THERAPY LA English DT Editorial Material ID PROGRESS; HEARING; VGLUT3 C1 [Holt, Jeffrey R.] Harvard Univ, Sch Med, Boston Childrens Hosp, FM Kirby Neurobiol Ctr,Dept Otolaryngol,Ctr Life, Boston, MA 02115 USA. [Vandenberghe, Luk H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. [Vandenberghe, Luk H.] Harvard Univ, Dept Ophthalmol, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. RP Holt, JR (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, FM Kirby Neurobiol Ctr,Dept Otolaryngol,Ctr Life, 300 Longwood Ave, Boston, MA 02115 USA. EM jeffrey.holt@childrens.harvard.edu; luk_vandenberghe@meei.harvard.edu RI Vandenberghe, Luk/B-4678-2008 OI Vandenberghe, Luk/0000-0002-3508-4924 FU NIDCD NIH HHS [R01 DC005439] NR 8 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD OCT PY 2012 VL 20 IS 10 BP 1836 EP 1837 DI 10.1038/mt.2012.196 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 016LE UT WOS:000309519000002 PM 23023054 ER PT J AU Fonseca, SG Urano, F Weir, GC Gromada, J Burcin, M AF Fonseca, Sonya G. Urano, Fumihiko Weir, Gordon C. Gromada, Jesper Burcin, Mark TI Wolfram syndrome 1 and adenylyl cyclase 8 interact at the plasma membrane to regulate insulin production and secretion (Retracted article. See vol. 17, pg. 105, 2015) SO NATURE CELL BIOLOGY LA English DT Article; Retracted Publication ID PANCREATIC BETA-CELLS; ENDOPLASMIC-RETICULUM STRESS; GLUCOSE; CAMP; WFS1; GENE; APOPTOSIS; GLP-1; MICE; EXOCYTOSIS AB Endoplasmic reticulum (ER) stress causes pancreatic beta-cell dysfunction and contributes to beta-cell loss and the progression of type 2 diabetes(1,2). Wolfram syndrome 1 (WFS1) has been shown to be an important regulator of the ER stress signalling pathway(3); however, its role in beta-cell function remains unclear. Here we provide evidence that WFS1 is essential for glucose-and glucagon-like peptide 1 (GLP-1)-stimulated cyclic AMP production and regulation of insulin biosynthesis and secretion. Stimulation with glucose causes WFS1 translocation from the ER to the plasma membrane, where it forms a complex with adenylyl cyclase 8 (AC8), an essential cAMP-generating enzyme in the beta-cell that integrates glucose and GLP-1 signalling(4). ER stress and mutant WFS1 inhibit complex formation and activation of AC8, reducing cAMP synthesis and insulin secretion. These findings reveal that an ER-stress-related protein has a distinct role outside the ER regulating both insulin biosynthesis and secretion. The reduction of WFS1 protein on the plasma membrane during ER stress is a contributing factor for beta-cell dysfunction and progression of type 2 diabetes. C1 [Fonseca, Sonya G.; Gromada, Jesper; Burcin, Mark] Novartis Inst BioMed Res, Cardiovasc & Metab Dis Area, Cambridge, MA 02139 USA. [Urano, Fumihiko] Washington Univ, Sch Med, Dept Med, Div Endocrinol Metab & Lipid Res, St Louis, MO 63110 USA. [Weir, Gordon C.] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Fonseca, SG (reprint author), Novartis Inst BioMed Res, Cardiovasc & Metab Dis Area, Cambridge, MA 02139 USA. EM sonya.fonseca@novartis.com FU NIH [DK067493, DK016746, P60 DK020579, RR024992, UL1 TR000448]; JDRF [11-2011-40] FX We thank M. Hara, Y. Adachi, Y. Murakami, L. Leahy, K. Sargent, B. O'Sullivan-Murphy, J. Hollister-Lock, J. Brown, K. Lipson, D. Ahern-Ridlon and X. Wang, for expert technical support; and C. Fonseca, S. Bonner-Weir and G. Waters for data discussions and comments on the manuscript. This work was supported by grants from the NIH (DK067493, DK016746, P60 DK020579, RR024992 and UL1 TR000448) and JDRF (11-2011-40) to F.U. NR 28 TC 36 Z9 36 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 EI 1476-4679 J9 NAT CELL BIOL JI Nat. Cell Biol. PD OCT PY 2012 VL 14 IS 10 BP 1105 EP + DI 10.1038/ncb2578 PG 15 WC Cell Biology SC Cell Biology GA 016UA UT WOS:000309543800019 PM 22983116 ER PT J AU Goldhirsch, A Gelber, RD AF Goldhirsch, Aron Gelber, Richard D. TI BREAST CANCER Anastrozole and fulvestrant-combination to unlock efficacy SO NATURE REVIEWS CLINICAL ONCOLOGY LA English DT Editorial Material ID TRIAL C1 [Goldhirsch, Aron] European Inst Oncol, Dept Med, I-20141 Milan, Italy. [Goldhirsch, Aron] St Anna Clin, Swiss Ctr Breast Hlth, CH-6924 Lugano, Switzerland. [Gelber, Richard D.] Dana Farber Canc Inst, IBCSG Stat Ctr, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Goldhirsch, A (reprint author), European Inst Oncol, Dept Med, Via Ripamonti 435, I-20141 Milan, Italy. EM aaron.goldhirsch@ieo.it NR 7 TC 2 Z9 2 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-4774 J9 NAT REV CLIN ONCOL JI Nat. Rev. Clin. Oncol. PD OCT PY 2012 VL 9 IS 10 BP 556 EP 557 DI 10.1038/nrclinonc.2012.155 PG 3 WC Oncology SC Oncology GA 016WP UT WOS:000309550800006 PM 22949048 ER PT J AU Armstrong, TS Wen, PY Gilbert, MR Schiff, D AF Armstrong, Terri S. Wen, Patrick Y. Gilbert, Mark R. Schiff, David TI Management of treatment-associated toxicites of anti-angiogenic therapy in patients with brain tumors SO NEURO-ONCOLOGY LA English DT Article DE brain tumors; chemotherapy; toxicity ID PHASE-II TRIAL; ENDOTHELIAL GROWTH-FACTOR; RECURRENT GLIOBLASTOMA-MULTIFORME; NEWLY-DIAGNOSED GLIOBLASTOMA; POSTERIOR LEUKOENCEPHALOPATHY SYNDROME; PATIENTS RECEIVING BEVACIZUMAB; SINGLE-AGENT BEVACIZUMAB; HIGH-GRADE GLIOMAS; VENOUS THROMBOEMBOLISM; MALIGNANT GLIOMA AB Anti-angiogenic therapies, including bevacizumab, are being used with increasing frequency in the management of malignant glioma. Common clinically significant toxicities include hypertension and proteinuria, poor wound healing, and the potential for thromboembolic events. Literature related to the use of bevacizumab in malignant glioma, reported toxicities in this patient population, and management of these toxicities was reviewed. Recommendations for assessment and management are provided. Anti-angiogenic therapies will continue to have a role in the treatment of malignant glioma. Further studies of the prevention, assessment, and management of these toxicities are warranted. C1 [Armstrong, Terri S.] Univ Texas MD Anderson Canc Ctr, Dept Integrat Nursing Care, UTHSC SON, Houston, TX 77030 USA. [Armstrong, Terri S.; Gilbert, Mark R.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. [Wen, Patrick Y.] Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. [Wen, Patrick Y.] Brigham & Womens Hosp, Div Neurooncol, Dept Neurol, Boston, MA 02115 USA. [Schiff, David] Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Schiff, David] Univ Virginia, Dept Neurol Surg, Charlottesville, VA USA. [Schiff, David] Univ Virginia, Dept Med Hematol Oncol, Charlottesville, VA USA. RP Armstrong, TS (reprint author), ANP BC, 6901 Bertner Ave, Houston, TX 77030 USA. EM terri.s.armstrong@uth.tmc.edu RI Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 NR 86 TC 27 Z9 27 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD OCT PY 2012 VL 14 IS 10 BP 1203 EP 1214 DI 10.1093/neuonc/nor223 PG 12 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 015RX UT WOS:000309464900002 PM 22307472 ER PT J AU Wong, ES Wang, BCM Alfonso-Cristancho, R Flum, DR Sullivan, SD Garrison, LP Arterburn, DE AF Wong, Edwin S. Wang, Bruce C. M. Alfonso-Cristancho, Rafael Flum, David R. Sullivan, Sean D. Garrison, Louis P. Arterburn, David E. TI BMI Trajectories Among the Severely Obese: Results From an Electronic Medical Record Population SO OBESITY LA English DT Article ID UNITED-STATES; CHILDHOOD OBESITY; SOCIOECONOMIC POSITION; OVERWEIGHT PREVALENCE; WEIGHT-GAIN; TRENDS; ADULTS; RACE/ETHNICITY; DISPARITIES; EPIDEMIC AB Epidemiological studies have documented the growing prevalence of severe obesity during the past three decades. The primary goal of this study was to estimate the trajectory of BMI change over 5+ years in a cohort of subjects identified as severely obese (BMI >= 35). We conducted a retrospective cohort study among adults enrolled in Group Health (GH) in Washington State. We tracked 11,735 subjects with at least one BMI measure of 35 or greater in the calendar year 2005 through April 2010. Population averaged BMI trajectories were estimated as a quadratic function of time using a marginal regression model, adjusting for gender and baseline BMI and age. For the average male in GH, the estimated BMI trajectory exhibited a slightly inverted U-shaped pattern and a 0.17 increase in BMI over the sample period. For the average female, the BMI trajectory was slightly U-shaped with BMI decreasing 0.03 units over the sample period. We found a high degree of heterogeneity in the shape of estimated trajectories across baseline characteristics with larger 5-year BMI increases among younger subjects with a lower initial BMI. We conclude that BMI changes over 5 years among individuals classified as severely obese are generally small and consistent with studies documenting BMI changes for individuals in other lower BMI categories. Our results also suggest that once the 35 BMI threshold is reached, individuals will continue to remain severely obese, especially at younger ages. C1 [Wong, Edwin S.; Wang, Bruce C. M.; Alfonso-Cristancho, Rafael; Sullivan, Sean D.; Garrison, Louis P.] Univ Washington, Pharmaceut Outcomes Res & Policy Program, Seattle, WA 98195 USA. [Wong, Edwin S.] VA Puget Sound Hlth Care Syst, NW Ctr Outcomes Res Older Adults, Seattle, WA USA. [Flum, David R.] Univ Washington, Surg Outcomes Res Ctr, Seattle, WA 98195 USA. [Arterburn, David E.] Grp Hlth Res Inst, Seattle, WA USA. RP Wong, ES (reprint author), Univ Washington, Pharmaceut Outcomes Res & Policy Program, Seattle, WA 98195 USA. EM eswong@uw.edu FU HQ Air Force [FA7014-08-2-0002]; Department of Veterans Affairs, Health Services Research, and Development Post-Doctoral Fellowship [TPP 61-024] FX This paper was written for the Bariatric Obesity Outcome Modeling Collaborative. Members are listed in Supplementary Appendix online. This work was supported by the HQ Air Force Surgeon General under Award No. FA7014-08-2-0002. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the U. S. Air Force. E. S. W. was supported by the Department of Veterans Affairs, Health Services Research, and Development Post-Doctoral Fellowship TPP 61-024. The authors thank Sebastien Haneuse, Matthew Maciejewski, Andy Bogart, Valerie Smith, Maren Olsen, Allyson Littman for their valuable input and suggestions. NR 24 TC 2 Z9 2 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD OCT PY 2012 VL 20 IS 10 BP 2107 EP 2112 DI 10.1038/oby.2012.29 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 016IH UT WOS:000309510700020 PM 22314622 ER PT J AU Parameswaran, S Spaeth-Rublee, B Huynh, PT Pincus, HA AF Parameswaran, Sharat Spaeth-Rublee, Brigitta Phuong Trang Huynh Pincus, Harold Alan TI Comparison of National Mental Health Quality Assessment Programs Across the Globe SO PSYCHIATRIC SERVICES LA English DT Article ID OUTCOME MEASUREMENT; IMPROVEMENT; CARE; PREVALENCE; DISORDERS AB Objective: This study by the International Initiative for Mental Health Leadership Clinical Leaders Project sought to describe ongoing or soon-to-be-established national-level mental health quality measurement programs in 12 participating countries, in order to understand the nature and structure of these programs. Methods: A survey was distributed to representatives from the participating countries (Australia, Canada, England, Germany, Ireland, Japan, the Netherlands, New Zealand, Norway, Scotland, Taiwan, and the United States). Data included descriptions of qualifying programs and the organizations responsible for them, quality indicators used, entities assessed, sources and means of the programs' data collection, the level at which data are reported, and how the data are used. Participants were asked to identify which quality domains and subdomains were represented by indicators in each program. Results were analyzed with descriptive statistics. Results: Thirty-eight programs were identified. Most programs were administered by governmental organizations, focused on hospital care, and used encounter or utilization databases as sources of information. Programs used different methods to identify indicators. Program data were used for various purposes. A wide range of domains of quality were represented in the programs reported, although most commonality was seen in domains associated with high-acuity care, with fewer programs assessing recovery-related domains. Conclusions: This study found wide variation among established quality assessment programs, which may reflect a focus on local priorities. The goal of this project is to work toward establishing an international framework for mental health quality assessment and thus a means to compare key measures of performance across countries. (Psychiatric Services 63:982,988, 2012; doi: 10.1176/appi.ps.201100382) C1 [Parameswaran, Sharat] Univ Calif Los Angeles, Robert Wood Johnson Fdn Clin Scholars, Los Angeles, CA 90024 USA. [Parameswaran, Sharat] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Clin Psychiat, Los Angeles, CA USA. [Spaeth-Rublee, Brigitta; Phuong Trang Huynh] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Pincus, Harold Alan] Columbia Univ, Dept Psychiat, New York, NY USA. RP Parameswaran, S (reprint author), Univ Calif Los Angeles, Robert Wood Johnson Fdn Clin Scholars, 10940 Wilshire Blvd,Suite 710-18, Los Angeles, CA 90024 USA. EM sharu@ucla.edu OI Iyer, Sharat/0000-0002-8576-7010 FU National Institute of Mental Health [R25 MH086466]; American Psychiatric Press FX Funding was provided by grant R25 MH086466 from the National Institute of Mental Health. Additional funding came from government and nongovernment organizations of the countries participating in the IIMHL project (Australia, Canada, England, Germany, Ireland, japan, the Netherlands, New Zealand, Norway, Scotland, Taiwan, and the United States). The authors thank the members of the IIMHL for their assistance with this project. Dr. Parameswaran is the recipient of an unrestricted educational grant from the American Psychiatric Institute for Research and Education and Janssen Pharmaceuticals.; Dr. Pincus receives travel support as a consultant for Value Options and publication royalties from the American Psychiatric Press and from Lippincott, Williams and Wilkins. The other authors report no competing interests. NR 21 TC 5 Z9 5 U1 6 U2 15 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 OCT PY 2012 VL 63 IS 10 BP 982 EP 988 DI 10.1176/appi.ps.201100382 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 015ZX UT WOS:000309488100006 ER PT J AU Kulkarni, NM Uppot, RN Eisner, BH Sahani, DV AF Kulkarni, Naveen M. Uppot, Raul N. Eisner, Brian H. Sahani, Dushyant V. TI Radiation Dose Reduction at Multidetector CT with Adaptive Statistical Iterative Reconstruction for Evaluation of Urolithiasis: How Low Can We Go? SO RADIOLOGY LA English DT Article ID UNENHANCED HELICAL CT; ACUTE FLANK PAIN; COMPUTED-TOMOGRAPHY; URETERAL CALCULI; INTRAVENOUS UROGRAPHY; UNITED-STATES; CANCER-RISKS; STONES; EPIDEMIOLOGY; FEASIBILITY AB Purpose: To evaluate the performance of computed tomographic (CT) examinations at 80 and 100 kV with tube current-time products of 75-150 mA and the effect of adaptive statistical iterative reconstruction (ASIR) on CT image quality in patients with urinary stone disease. Materials and Methods: In this HIPAA-compliant institutional review board-approved study, verbal consent for prospective low-dose CT and waivers of consent for retrospective review of CT scans were obtained. Between November 2010 and April 2011, 25 patients (15 men, 10 women; mean age, 35 years) with urolithiasis underwent 64-section multidetector CT with 75-150 mA and noise index of 30. Modified protocol was based on body weight (<200 lb [90 kg], 80 kV; >200 lb [90 kg], 100 kV). Images of 5-mm section thickness were reconstructed with filtered back projection (FBP) and 60% and 80% ASIR techniques, with 3-mm coronal and sagittal reformations. Two readers independently reviewed FBP and ASIR data sets for image quality (scale, 1-5), noise (scale, 1-3), and calculi (number, size, location). Confidence levels for urolithiaisis and alternate diagnoses were rated (scale, 1-3). In 13 patients, FBP CT images acquired with the reference standard departmental protocol were available for comparison. Radiation dose was compared between imaging series. Statistical analysis was performed with Wilcoxon signed rank and paired t tests. Results: Modified-protocol FBP images showed low image quality (score, 2.5), with improvement on modified-protocol ASIR images (score, 3.4) (P = .03). All 33 stones (mean diameter, 6.1 mm; range, 2-28 mm) at modified-protocol CT were diagnosed by both readers. In 20 of 25 patients (80%), ASIR images were rated adequate for rendering other diagnoses in the abdomen (score, 2.0), as opposed to FBP images (score, 1.3). Mean radiation dose for modified-protocol CT was 1.8 mGy (1.3 mGy for patients < 200 lb; 2.3 mGy for patients > 200 lb) in comparison with 9.9 mGy for reference-protocol CT (P = .001). Conclusion: Image quality improvements with ASIR at reduced radiation dose of 1.8 mGy enabled effective evaluation of urinary calculi without substantially affecting diagnostic confidence. (C) RSNA, 2012 C1 [Kulkarni, Naveen M.; Uppot, Raul N.; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Eisner, Brian H.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org FU AJR/ARRS Figley Fellowship; GE Healthcare; SGR FX N.M.K. No potential conflicts of interest to disclose. R.N.U. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: received payment as an expert reviewer on a legal case by Robison, Curphey & O'Connell; received a grant for study on quantifying abdominal fat from SGR and received the AJR/ARRS Figley Fellowship. Other relationships: none to disclose. B. H. E. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: none to disclose. Other relationships: is a consultant for Boston Scientific, PercSys, Olympus/ACMI Owner, Ravine Group. D. V. S. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: received payment for consultancy from Bracco Diagnostics; institution received grants from GE Healthcare for dualenergy CT pilot study and from BD for CM extravasations in CT; received royalties from Elsevier for textbook. Other relationships: none to disclose. NR 32 TC 62 Z9 67 U1 1 U2 10 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2012 VL 265 IS 1 BP 158 EP 166 DI 10.1148/radiol.12112470 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 016KR UT WOS:000309517600019 PM 22891359 ER PT J AU In, H Greenberg, CC AF In, Haejin Greenberg, Caprice C. TI Lack of Uniformity in Levels of Evidence and Recommendation Grades in Surgical Oncology Guidelines SO WORLD JOURNAL OF SURGERY LA English DT Editorial Material ID QUALITY C1 [In, Haejin] Univ Chicago, Dept Surg, Med Ctr, Chicago, IL 60637 USA. [In, Haejin; Greenberg, Caprice C.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Dept Surg, Boston, MA 02115 USA. [In, Haejin] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Greenberg, Caprice C.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med Oncol, Boston, MA 02115 USA. RP In, H (reprint author), Univ Chicago, Dept Surg, Med Ctr, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM Haejin.In@uchospitals.edu FU NCI NIH HHS [R25 CA092203, L30 CA123695] NR 10 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD OCT PY 2012 VL 36 IS 10 BP 2273 EP 2275 DI 10.1007/s00268-012-1630-0 PG 3 WC Surgery SC Surgery GA 017AA UT WOS:000309559800001 PM 22543721 ER PT J AU Colman, RJ Beasley, TM Allison, DB Weindruch, R AF Colman, Ricki J. Beasley, T. Mark Allison, David B. Weindruch, Richard TI Skeletal effects of long-term caloric restriction in rhesus monkeys SO AGE LA English DT Article DE Caloric restriction; Bone; Aging; Osteoporosis; Dietary restriction; Dual-energy x-ray absorptiometry ID BONE-MINERAL DENSITY; DIETARY RESTRICTION; FOOD RESTRICTION; BODY-COMPOSITION; MACACA-MULATTA; TENNIS PLAYERS; ADULT MALE; WOMEN; AGE; OSTEOPOROSIS AB Age-related bone loss is well established in humans and is known to occur in nonhuman primates. There is little information, however, on the effect of dietary interventions, such as caloric restriction (CR), on age-related bone loss. This study examined the effects of long-term, moderate CR on skeletal parameters in rhesus monkeys. Thirty adult male rhesus monkeys were subjected to either a restricted (R, n = 15) or control (C, n = 15) diet for 20 years and examined throughout for body composition and biochemical markers of bone turnover. Total body, spine, and radius bone mass and density were assessed by dual-energy X-ray absorptiometry. Assessment of biochemical markers of bone turnover included circulating serum levels of osteocalcin, carboxyterminal telopeptide of type I collagen, cross-linked aminoterminal telopeptide of type I collagen, parathyroid hormone, and 25(OH)vitamin D. Overall, we found that bone mass and density declined over time with generally higher levels in C compared to R animals. Circulating serum markers of bone turnover were not different between C and R with nonsignficant diet-by-time interactions. We believe the lower bone mass in R animals reflects the smaller body size and not pathological osteopenia. C1 [Colman, Ricki J.] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA. [Beasley, T. Mark; Allison, David B.] Univ Alabama Birmingham, Dept Biostat, Birmingham, AL 35294 USA. [Weindruch, Richard] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53706 USA. [Weindruch, Richard] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI 53705 USA. RP Colman, RJ (reprint author), Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA. EM rcolman@primate.wisc.edu OI Allison, David/0000-0003-3566-9399 FU National Institutes of Health [P01 AG-11915, P51 RR000167]; Research Facilities Improvement Program [RR15459-01, RR020141-01] FX We acknowledge the excellent technical assistance provided by S. Baum, J. Christensen, J. A. Adriansjach, C. E. Armstrong, and the Animal Care and Veterinary Staff of the WNPRC. This work was supported by National Institutes of Health grants P01 AG-11915 and P51 RR000167. This research was conducted in part at the WNPRC, which received support from Research Facilities Improvement Program grant numbers RR15459-01 and RR020141-01. This research was supported in part by facilities and resources at the Wm. S. Middleton Memorial Veterans Hospital. NR 70 TC 6 Z9 6 U1 0 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0161-9152 J9 AGE JI Age PD OCT PY 2012 VL 34 IS 5 BP 1133 EP 1143 DI 10.1007/s11357-011-9354-x PG 11 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 011NB UT WOS:000309170600007 PM 22189911 ER PT J AU Ackerson, LK Ramanadhan, S Arya, M Viswanath, K AF Ackerson, Leland K. Ramanadhan, Shoba Arya, Monisha Viswanath, Kasisomayajula TI Social Disparities, Communication Inequalities, and HIV/AIDS-Related Knowledge and Attitudes in India SO AIDS AND BEHAVIOR LA English DT Article DE AIDS; Health communication; HIV; India; Socioeconomic status; Communication inequalities ID MASS-MEDIA; HIV; HEALTH; CAMPAIGNS; STIGMA; METAANALYSIS; BEHAVIOR; PEOPLE; STATES; WOMEN AB Promoting awareness, increasing knowledge, and eliminating stigma is important for stopping the spread of HIV/AIDS. The relation of social determinants and communication inequalities with HIV/AIDS-related cognitive processes has not been studied previously in India. Gender-stratified Poisson regression models of 123,459 women and 73,908 men in the 2005-2006 National Family Health Survey were used to calculate relative risk estimates and 95% confidence intervals for these associations. Results indicated that there are significant inequalities in mass media use among different social classes. Education and wealth are strongly and positively associated with awareness of HIV/AIDS and knowledge about prevention and transmission of AIDS and negatively associated with HIV/AIDS-related stigma. These associations attenuated when use of various mass media types were added to the models with television showing the strongest effect. Mass media may be helpful in reducing social disparities in HIV/AIDS outcomes. C1 [Ackerson, Leland K.] Univ Massachusetts, Dept Community Hlth & Sustainabil, Lowell, MA 01854 USA. [Ramanadhan, Shoba; Viswanath, Kasisomayajula] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Arya, Monisha] Baylor Coll Med, Infect Dis Sect, Houston, TX 77030 USA. [Viswanath, Kasisomayajula] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Ackerson, LK (reprint author), Univ Massachusetts, Dept Community Hlth & Sustainabil, 3 Solomont Way,Suite 3, Lowell, MA 01854 USA. EM Leland_Ackerson@uml.edu FU NCI NIH HHS [U01 CA114644-05, R01 CA122894-01] NR 45 TC 6 Z9 7 U1 3 U2 13 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS Behav. PD OCT PY 2012 VL 16 IS 7 BP 2072 EP 2081 DI 10.1007/s10461-011-0031-y PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 012GC UT WOS:000309223000040 PM 21870161 ER PT J AU Freedman, A AF Freedman, Arnold TI Follicular lymphoma: 2012 update on diagnosis and management SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Review ID NON-HODGKINS-LYMPHOMA; STEM-CELL TRANSPLANTATION; HIGH-DOSE THERAPY; TERM-FOLLOW-UP; ANTI-CD20 MONOCLONAL-ANTIBODY; RANDOMIZED CONTROLLED-TRIAL; PROGRESSION-FREE SURVIVAL; INDOLENT B-CELL; PHASE-II TRIAL; INTERNATIONAL PROGNOSTIC INDEX AB Disease overview: Follicular lymphoma (FL) is generally an indolent B-cell lymphoproliferative disorder of transformed follicular center B cells. FL is characterized by diffuse lymphoadenopathy, involvement of bone marrow, splenomegaly, and less commonly other extranodal sites of involvement. In general, cytopenias can occur but constitutional symptoms of fever, nightsweats, and weight loss are uncommon. Diagnosis: Diagnosis is based on histology of preferably a biopsy of a lymph node. Immunohistochemical staining is positive in virtually all cases for cell surface CD19, CD20, CD10, and monoclonal immunoglobulin, as well as cytoplasmic expression of bcl-2 protein. The overwhelming majority of cases have the characteristic t(14;18) translocation involving the IgH/bcl-2 genes. Risk stratification: The FL International Prognostic Index prognostic model for FL uses five independent predictors of inferior survival: age > 60 years, hemoglobin < 12 g/dL, serum lactate dehydrogenase > normal, Ann Arbor stage III/IV, number of involved nodal areas > 4. The presence of 0, 1, 2, and = 3 adverse factors defines low, intermediate, and high-risk disease with median 10-year survivals in the pre-rituximab era of 71, 51, and 36 months, respectively. With the use of more modern therapies, specifically anti-CD20 monoclonal antibody, the outcome has improved. Risk-adapted therapy: Observation continues to be adequate for asymptomatic patients with low bulk disease and no cytopenias. For patients needing therapy, most patients are treated with chemotherapy plus rituximab, which has improved response rates, duration of response, and overall survival. Randomized studies have shown additional benefit for maintenance rituximab both following chemotherapy-rituximab and single-agent rituximab. Autologous stem cell transplantation (SCT) has not shown a survival benefit in first remission patients. SCT including both autologous and allogeneic SCT or experimental agent therapy is considered for recurrent disease. Am. J. Hematol. (c) 2012 Wiley Periodicals, Inc. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Freedman, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM afreedman@partners.org NR 117 TC 24 Z9 28 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD OCT PY 2012 VL 87 IS 10 BP 988 EP 995 DI 10.1002/ajh.23313 PG 8 WC Hematology SC Hematology GA 010AB UT WOS:000309065700086 PM 23001911 ER PT J AU Hart, JE Wu, TY Laden, F Garshick, E AF Hart, Jaime E. Wu, Tianying Laden, Francine Garshick, Eric TI Plasma fluorescent oxidation products and short-term occupational particulate exposures SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE vehicle emissions; biomarkers; oxidative stress; trucking industry; diesel ID US TRUCKING INDUSTRY; CAUSE-SPECIFIC MORTALITY; CITY BUS DRIVERS; AIR-POLLUTION; DNA-DAMAGE; MYOCARDIAL-INFARCTION; LIPID-PEROXIDATION; STRESS MARKERS; INFLAMMATORY MARKERS; SEASONAL VARIABILITY AB Background Evidence suggests that fine particulate air pollution results in oxidative induced tissue damage. Methods A global fluorescent oxidation products (FLOx) assay (fluorescent intensity (FI) units per milliliter of plasma) was measured in blood samples collected from 236 nonsmoking, Caucasian, male trucking industry workers either prior to, during, or after their work shifts. Occupational exposures to particulate matter (PM)2.5 were based on job-specific area-level sampling. Generalized linear models were used to determine associations between FLOx levels and PM2.5, adjusted for age, time since last meal, alcohol consumption, aspirin, and cholesterol medications. Results The mean (standard deviation) level of FLOx was 265.9 FI/ml (96.0). Levels of FLOx were higher among older individuals and lower among those who had consumed alcohol in the past 24 hr. However, no associations were observed between FLOx and PM2.5. Conclusions Our results indicate no association between occupational PM2.5 exposure and this marker of global oxidative stress. Am. J. Ind. Med. 55:953960, 2012. (C) 2012 Wiley Periodicals, Inc. C1 [Hart, Jaime E.; Laden, Francine; Garshick, Eric] Harvard Univ, Sch Med, Boston, MA USA. [Hart, Jaime E.; Laden, Francine; Garshick, Eric] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Hart, Jaime E.; Laden, Francine] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Wu, Tianying] Univ Cincinnati, Med Ctr, Dept Environm Hlth, Div Epidemiol & Biostat, Cincinnati, OH 45267 USA. [Laden, Francine] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program, Boston, MA 02115 USA. [Garshick, Eric] VA Boston Healthcare Syst, Med Serv, Pulm & Crit Care Med Sect, Boston, MA USA. RP Hart, JE (reprint author), 181 Longwood Ave, Boston, MA 02115 USA. EM jaime.hart@channing.harvard.edu OI Yang, Shuman/0000-0002-9638-0890 FU National Institutes of Health (NIH)/NIEHS [R21 ES013726, P30 ES00002, T32 ES007069-29] FX We thank Marina Jacobson Canner for programming assistance and Serena Hon, Andrew Blicharz, Kirby Matthess, and Kelly Stolzmann for assistance in field collection. This study was supported by National Institutes of Health (NIH)/NIEHS grant R21 ES013726, NIH/NIEHS Center grant P30 ES00002, and NIH/NIEHS T32 ES007069-29 (Dr. Hart). NR 60 TC 1 Z9 1 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD OCT PY 2012 VL 55 IS 10 BP 953 EP 960 DI 10.1002/ajim.22073 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 003SP UT WOS:000308631900010 PM 22618714 ER PT J AU Liu, JR Zhang, W Chuang, GC Hill, HS Tian, L Fu, YC Moellering, DR Garvey, WT AF Liu, Jiarong Zhang, Wei Chuang, Gin C. Hill, Helliner S. Tian, Ling Fu, Yuchang Moellering, Douglas R. Garvey, W. Timothy TI Role of TRIB3 in regulation of insulin sensitivity and nutrient metabolism during short-term fasting and nutrient excess SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE tribbles 3; glucose oxidation; nutrient sensor; skeletal muscle; adipose tissue; adipocyte; mitochondria; glucose transport; glucose oxidation ID SKELETAL-MUSCLE; GENE-EXPRESSION; MITOCHONDRIAL BIOGENESIS; OXIDATIVE STRESS; DIABETIC COMPLICATIONS; TRIBBLES HOMOLOG; MESSENGER-RNA; CELL-FUNCTION; TRB3; INDUCTION AB Liu J, Zhang W, Chuang GC, Hill HS, Tian L, Fu Y, Moellering DR, Garvey WT. Role of TRIB3 in regulation of insulin sensitivity and nutrient metabolism during short-term fasting and nutrient excess. Am J Physiol Endocrinol Metab 303: E908-E916, 2012. First published July 31, 2012; doi:10.1152/ajpendo.00663.2011.-We have suggested previously that Tribbles homolog 3 (TRIB3), a negative regulator of Akt activity in insulin-sensitive tissues, could mediate glucose-induced insulin resistance in muscle under conditions of chronic hyperglycemia (Liu J, Wu X, Franklin JL, Messina JL, Hill HS, Moellering DR, Walton RG, Martin M, Garvey WT. Am J Physiol Endocrinol Metab 298: E565-E576, 2010). In the current study, we have assessed short-term physiological regulation of TRIB3 in skeletal muscle and adipose tissues by nutrient excess and fasting as well as TRIB3's ability to modulate glucose transport and mitochondrial oxidation. In Sprague-Dawley rats, we found that short-term fasting enhanced insulin sensitivity concomitantly with decrements in TRIB3 mRNA (66%, P < 0.05) and protein (81%, P < 0.05) in muscle and increments in TRIB3 mRNA (96%, P < 0.05) and protein (similar to 10-fold, P < 0.05) in adipose tissue compared with nonfasted controls. On the other hand, rats fed a Western diet for 7 days became insulin resistant concomitantly with increments in TRIB3 mRNA (155%, P < 0.05) and protein (69%, P = 0.0567) in muscle and a decrease in the mRNA (76%, P < 0.05) and protein (70%, P < 0.05) in adipose. In glucose transport and mitochondria oxidation studies using skeletal muscle cells, we found that stable TRIB3 overexpression impaired insulin-stimulated glucose uptake without affecting basal glucose transport and increased both basal glucose oxidation and the maximal uncoupled oxygen consumption rate. With stable knockdown of TRIB3, basal and insulin-stimulated glucose transport rates were increased, whereas basal glucose oxidation and the maximal uncoupled oxygen consumption rate were decreased. In conclusion, TRIB3 impacts glucose uptake and oxidation oppositely in muscle and fat according to levels of nutrient availability. The above data for the first time implicate TRIB3 as a potent physiological regulator of insulin sensitivity and mitochondrial glucose oxidation under conditions of nutrient deprivation and excess. C1 [Zhang, Wei; Tian, Ling; Moellering, Douglas R.; Garvey, W. Timothy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA. [Liu, Jiarong; Chuang, Gin C.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA. [Chuang, Gin C.; Moellering, Douglas R.] Univ Alabama Birmingham, Comprehens Diabet Ctr, Diabet Res & Training Ctr, Birmingham, AL USA. [Chuang, Gin C.; Moellering, Douglas R.] Univ Alabama Birmingham, Bioanalyt Redox Biol Core, Birmingham, AL USA. [Hill, Helliner S.] Novo Nordisk, Field Med Affairs Diabet, Princeton, NJ USA. [Garvey, W. Timothy] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Garvey, WT (reprint author), Univ Alabama Birmingham, Dept Nutr Sci, 1675 Univ Blvd, Birmingham, AL 35294 USA. EM garveyt@uab.edu RI Chuang, Gin/J-6510-2012 OI Chuang, Gin/0000-0003-3919-1820 FU National Institute of Diabetes and Digestive and Kidney Diseases [DK-038765, DK-083562]; Merit Review Program of the Department of Veterans Affairs; University of Alabama at Birmingham Diabetes Research and Training Center [P60 DK-079626] FX This work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (DK-038765, DK-083562) and by the Merit Review Program of the Department of Veterans Affairs.; We acknowledge support from core facilities of the University of Alabama at Birmingham Diabetes Research and Training Center (P60 DK-079626). NR 50 TC 9 Z9 9 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 EI 1522-1555 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD OCT PY 2012 VL 303 IS 7 BP E908 EP E916 DI 10.1152/ajpendo.00663.2011 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 016HF UT WOS:000309507700011 PM 22850683 ER PT J AU Inoue, T Wang, JH Higashiyama, M Rudenkyy, S Higuchi, K Guth, PH Engel, E Kaunitz, JD Akiba, Y AF Inoue, Takuya Wang, Joon-Ho Higashiyama, Masaaki Rudenkyy, Sergiy Higuchi, Kazuhide Guth, Paul H. Engel, Eli Kaunitz, Jonathan D. Akiba, Yasutada TI Dipeptidyl peptidase IV inhibition potentiates amino acid- and bile acid-induced bicarbonate secretion in rat duodenum SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE glucagon-like peptide-2; L cells; TGR5; monosodium glutamate; taste receptor ID GLUCAGON-LIKE PEPTIDE-1; L CELLS; ABSORPTION; RECEPTORS; INTESTINE; PROTEIN; MUCOSA; EPAC; RAP1; PIGS AB Inoue T, Wang JH, Higashiyama M, Rudenkyy S, Higuchi K, Guth PH, Engel E, Kaunitz JD, Akiba Y. Dipeptidyl peptidase IV inhibition potentiates amino acid-and bile acid-induced bicarbonate secretion in rat duodenum. Am J Physiol Gastrointest Liver Physiol 303: G810-G816, 2012. First published July 19, 2012; doi:10.1152/ajpgi.00195.2012.-Intestinal endocrine cells release gut hormones, including glucagon-like peptides (GLPs), in response to luminal nutrients. Luminal L-glutamate (L-Glu) and 5'-inosine monophosphate (IMP) synergistically increases duodenal HCO3- secretion via GLP-2 release. Since L cells express the bile acid receptor TGR5 and dipeptidyl peptidase (DPP) IV rapidly degrades GLPs, we hypothesized that luminal amino acids or bile acids stimulate duodenal HCO3- secretion via GLP-2 release, which is enhanced by DPPIV inhibition. We measured HCO3- secretion with pH and CO2 electrodes using a perfused rat duodenal loop under isoflurane anesthesia. L-Glu (10 mM) and IMP (0.1 mM) were luminally coperfused with or without luminal perfusion (0.1 mM) or intravenous (iv) injection (3 mu mol/kg) of the DPPIV inhibitor NVP728. The loop was also perfused with a selective TGR5 agonist betulinic acid (BTA, 10 mu M) or the non-bile acid type TGR5 agonist 3-(2-chlorophenyl)-N-(4-chlorophenyl)-N,5-dimethylisoxazole-4-carboxamide (CCDC; 10 mu M). DPPIV activity visualized by use of the fluorogenic substrate was present on the duodenal brush border and submucosal layer, both abolished by the incubation with NVP728 (0.1 mM). An iv injection of NVP728 enhanced L-Glu/IMP-induced HCO3- secretion, whereas luminal perfusion of NVP728 had no effect. BTA or CCDC had little effect on HCO3- secretion, whereas NVP728 iv markedly enhanced BTA- or CCDC-induced HCO3- secretion, the effects inhibited by a GLP-2 receptor antagonist. Coperfusion of the TGR5 agonist enhanced L-Glu/IMP-induced HCO3 secretion with the enhanced GLP-2 release, suggesting that TGR5 activation amplifies nutrient sensing signals. DPPIV inhibition potentiated luminal L-Glu/IMP-induced and TGR5 agonist-induced HCO3- secretion via a GLP-2 pathway, suggesting that the modulation of the local concentration of the endogenous secretagogue GLP-2 by luminal compounds and DPPIV inhibition helps regulate protective duodenal HCO3- secretion. C1 [Rudenkyy, Sergiy; Guth, Paul H.; Kaunitz, Jonathan D.; Akiba, Yasutada] Univ Calif Los Angeles, Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. [Inoue, Takuya; Wang, Joon-Ho; Higashiyama, Masaaki; Kaunitz, Jonathan D.; Akiba, Yasutada] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. [Kaunitz, Jonathan D.; Akiba, Yasutada] Univ Calif Los Angeles, Dept Biomath, Los Angeles, CA USA. [Kaunitz, Jonathan D.; Akiba, Yasutada] Brentwood Biomed Res Inst, Los Angeles, CA USA. [Inoue, Takuya; Higuchi, Kazuhide] Osaka Med Coll, Dept Internal Med 2, Osaka, Japan. RP Akiba, Y (reprint author), W Los Angeles VA Med Ctr, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM yakiba@mednet.ucla.edu FU Ajinomoto, Japan; Department of Veterans Affairs Merit Review Award; NIH-NIDDK [R01 DK54221, P30 DK0413] FX This research was supported by a research grant from Ajinomoto, Japan (Y. Akiba), Department of Veterans Affairs Merit Review Award, NIH-NIDDK R01 DK54221 (J. Kaunitz), and the animal core of NIH-NIDDK P30 DK0413 (J. E. Rozengurt). NR 40 TC 12 Z9 12 U1 0 U2 13 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD OCT PY 2012 VL 303 IS 7 BP G810 EP G816 DI 10.1152/ajpgi.00195.2012 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 016HJ UT WOS:000309508100004 PM 22821947 ER PT J AU Gallagher, PJ Castro, V Fava, M Weilburg, JB Murphy, SN Gainer, VS Churchill, SE Kohane, IS Iosifescu, DV Smoller, JW Perlis, RH AF Gallagher, Patience J. Castro, Victor Fava, Maurizio Weilburg, Jeffrey B. Murphy, Shawn N. Gainer, Vivian S. Churchill, Susanne E. Kohane, Isaac S. Iosifescu, Dan V. Smoller, Jordan W. Perlis, Roy H. TI Antidepressant Response in Patients With Major Depression Exposed to NSAIDs: A Pharmacovigilance Study SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ELECTRONIC MEDICAL-RECORDS; ILLNESS RATING-SCALE; COMORBIDITY; VALIDATION; ENTERPRISE; DISORDER; BURDEN; SSRIS; CARE AB Objective: It has been suggested that there is a mechanism by which nonsteroidal anti-inflammatory drugs (NSAIDs) may interfere with antidepressant response, and poorer outcomes among NSAID-treated patients were reported in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. To attempt to confirm this association in an independent population-based treatment cohort and explore potential confounding variables, the authors examined use of NSAIDs and related medications among 1,528 outpatients in a New England health care system. Method: Treatment outcomes were classified using a validated machine learning tool applied to electronic medical records. Logistic regression was used to examine the association between medication exposure and treatment outcomes, adjusted for potential confounding variables. To further elucidate confounding and treatment specificity of the observed effects, data from the STAR*D study were reanalyzed. Results: NSAID exposure was associated with a greater likelihood of depression classified as treatment resistant compared with depression classified as responsive to selective serotonin reuptake inhibitors (odds ratio=1.55, 95% CI=1.21-2.00). This association was apparent in the NSAIDs-only group but not in those using other agents with NSAID-like mechanisms (cyclooxygenase-2 inhibitors and salicylates). Inclusion of age, sex, ethnicity, and measures of comorbidity and health care utilization in regression models indicated confounding; association with outcome was no longer significant in fully adjusted models. Reanalysis of STAR*D results likewise identified an association in NSAIDs but not NSAID-like drugs, with more modest effects persisting after adjustment for potential confounding variables. Conclusions: These results support an association between NSAID use and poorer antidepressant outcomes in major depressive disorder but indicate that some of the observed effect may be a result of confounding. (Am J Psychiatry 2012; 169:1065-1072) C1 [Perlis, Roy H.] Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. Partners HealthCare Syst, Partners Res Comp, Boston, MA USA. Massachusetts Gen Hosp, Depress Clin, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Partners HealthCare Syst, Informat Syst, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Massachusetts Gen Hosp, Dept Psychiat, Res Program, Boston, MA 02114 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. EM rperlis@partners.org RI Kohane, Isaac Kohane/K-3716-2012 OI Kohane, Isaac Kohane/0000-0003-2192-5160 FU Abbott Laboratories; Alkermes; Aspect Medical Systems; AstraZeneca; Bristol-Myers Squibb; Cephalon; Eli Lilly; Forest Pharmaceuticals; GlaxoSmithKline; J & J Pharmaceuticals; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Novartis; Organon; PamLab; Pfizer; Pharmavite; Roche; Sanofi/Synthelabo; Solvay Pharmaceuticals; Wyeth-Ayerst Laboratories; Bayer AG; Biovail Pharmaceuticals; BrainCells; Compellis; Cypress Pharmaceuticals; Dov Pharmaceuticals; EPIX Pharmaceuticals; Fabre-Kramer Pharmaceuticals; Grunenthal GmBH; Janssen Pharmaceutica; Jazz Pharmaceuticals; Knoll Pharmaceutical Company; Lundbeck; MedAvante; Neuronetics; Nutrition 21; PharmaStar; Sepracor; Somaxon; Somerset Pharmaceuticals; Boehringer-Ingelheim; Forest Laboratories; Janssen Pharmaceuticals; NARSAD; NIH; Proteus Biomedical; Genomind; RidVentures; National Library of Medicine [U54LM008748]; NIMH [R01MH-086026] FX Dr. Fava has received research support from Abbott Laboratories, Alkermes, Aspect Medical Systems, AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest Pharmaceuticals, GlaxoSmithKline, J & J Pharmaceuticals, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, Novartis, Organon, PamLab, Pfizer, Pharmavite, Roche, Sanofi/Synthelabo, Solvay Pharmaceuticals, and Wyeth-Ayerst Laboratories; he has received advisory/consulting fees from Aspect Medical Systems, AstraZeneca, Bayer AG, Biovail Pharmaceuticals, BrainCells, Bristol-Myers Squibb, Cephalon, Compellis, Cypress Pharmaceuticals, Dov Pharmaceuticals, Eli Lilly, EPIX Pharmaceuticals, Fabre-Kramer Pharmaceuticals, Forest Pharmaceuticals, GlaxoSmithKline, Grunenthal GmBH, Janssen Pharmaceutica, Jazz Pharmaceuticals, J & J Pharmaceuticals, Knoll Pharmaceutical Company, Lundbeck, MedAvante, Neuronetics, Novartis, Nutrition 21, Organon, PamLab, Pfizer, PharmaStar, Pharmavite, Roche, Sanofi/Synthelabo, Sepracor, Solvay Pharmaceuticals, Somaxon, Somerset Pharmaceuticals, and Wyeth-Ayerst Laboratories; and he has received speaking fees from AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest Pharmaceuticals, GlaxoSmithKline, Novartis, Organon, Pfizer, PharmaStar, and Wyeth-Ayerst Laboratories. Dr. Iosifescu has served as a consultant to CNS Response; he has received grant support from Aspect Medical Systems, Forest Laboratories, Janssen Pharmaceuticals, NARSAD, and NIH; he has received speaker's honoraria from Eli Lilly, Pfizer, Forest Laboratories, and Reed Medical Education. Dr. Perlis has received research support from Proteus Biomedical; he has received advisory/consulting fees from Eli Lilly, Genomind, Proteus Biomedical, and RidVentures; and he has equity holdings and patents with Concordant Rater Systems. The other authors report no financial relationships with commercial interests.; Supported by the National Library of Medicine award U54LM008748 (to Dr. Kohane) and NIMH grant R01MH-086026 (to Dr. Perlis). NR 21 TC 26 Z9 27 U1 1 U2 14 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD OCT PY 2012 VL 169 IS 10 BP 1065 EP 1072 DI 10.1176/appi.ajp.2012.11091325 PG 8 WC Psychiatry SC Psychiatry GA 015HS UT WOS:000309437600012 PM 23032386 ER PT J AU Wilk, JB Shrine, NRG Loehr, LR Zhao, JH Manichaikul, A Lopez, LM Smith, AV Heckbert, SR Smolonska, J Tang, WB Loth, DW Curjuric, I Hui, J Cho, MH Latourelle, JC Henry, AP Aldrich, M Bakke, P Beaty, TH Bentley, AR Borecki, IB Brusselle, GG Burkart, KM Chen, TH Couper, D Crapo, JD Davies, G Dupuis, J Franceschini, N Gulsvik, A Hancock, DB Harris, TB Hofman, A Imboden, M James, AL Khaw, KT Lahousse, L Launer, LJ Litonjua, A Liu, YM Lohman, KK Lomas, DA Lumley, T Marciante, KD McArdle, WL Meibohm, B Morrison, AC Musk, AW Myers, RH North, KE Postma, DS Psaty, BM Rich, SS Rivadeneira, F Rochat, T Rotter, JI Artigas, MS Starr, JM Uitterlinden, AG Wareham, NJ Wijmenga, C Zanen, P Province, MA Silverman, EK Deary, IJ Palmer, LJ Cassano, PA Gudnason, V Barr, RG Loos, RJF Strachan, DP London, SJ Boezen, HM Probst-Hensch, N Gharib, SA Hall, IP O'Connor, GT Tobin, MD Stricker, BH AF Wilk, Jemma B. Shrine, Nick R. G. Loehr, Laura R. Zhao, Jing Hua Manichaikul, Ani Lopez, Lorna M. Smith, Albert Vernon Heckbert, Susan R. Smolonska, Joanna Tang, Wenbo Loth, Daan W. Curjuric, Ivan Hui, Jennie Cho, Michael H. Latourelle, Jeanne C. Henry, Amanda P. Aldrich, Melinda Bakke, Per Beaty, Terri H. Bentley, Amy R. Borecki, Ingrid B. Brusselle, Guy G. Burkart, Kristin M. Chen, Ting-hsu Couper, David Crapo, James D. Davies, Gail Dupuis, Josee Franceschini, Nora Gulsvik, Amund Hancock, Dana B. Harris, Tamara B. Hofman, Albert Imboden, Medea James, Alan L. Khaw, Kay-Tee Lahousse, Lies Launer, Lenore J. Litonjua, Augusto Liu, Yongmei Lohman, Kurt K. Lomas, David A. Lumley, Thomas Marciante, Kristin D. McArdle, Wendy L. Meibohm, Bernd Morrison, Alanna C. Musk, Arthur W. Myers, Richard H. North, Kari E. Postma, Dirkje S. Psaty, Bruce M. Rich, Stephen S. Rivadeneira, Fernando Rochat, Thierry Rotter, Jerome I. Artigas, Maria Soler Starr, John M. Uitterlinden, Andre G. Wareham, Nicholas J. Wijmenga, Cisca Zanen, Pieter Province, Michael A. Silverman, Edwin K. Deary, Ian J. Palmer, Lyle J. Cassano, Patricia A. Gudnason, Vilmundur Barr, R. Graham Loos, Ruth J. F. Strachan, David P. London, Stephanie J. Boezen, H. Marike Probst-Hensch, Nicole Gharib, Sina A. Hall, Ian P. O'Connor, George T. Tobin, Martin D. Stricker, Bruno H. TI Genome-Wide Association Studies Identify CHRNA5/3 and HTR4 in the Development of Airflow Obstruction SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE chronic obstructive pulmonary disease; single-nucleotide polymorphism; genes ID NICOTINIC ACETYLCHOLINE-RECEPTOR; PULMONARY-DISEASE; LUNG-CANCER; SUSCEPTIBILITY LOCUS; SMOKING-BEHAVIOR; 15Q25 LOCUS; RISK; EXPRESSION; VARIANTS; COPD AB Rationale: Genome-wide association studies (GWAS) have identified loci influencing lung function, but fewer genes influencing chronic obstructive pulmonary disease (COPD) are known. Objectives: Perform meta-analyses of GWAS for airflow obstruction, a key pathophysiologic characteristic of COPD assessed by spirometry, in population-based cohorts examining all participants, ever smokers, never smokers, asthma-free participants, and more severe cases. Methods: Fifteen cohorts were studied for discovery (3,368 affected; 29,507 unaffected), and a population-based family study and a meta-analysis of case-control studies were used for replication and regional follow-up (3,837 cases; 4,479 control subjects). Airflow obstruction was defined as FEV1 and its ratio to FVC (FEV1/FVC) both less than their respective lower limits of normal as determined by published reference equations. Measurements and Main Results: The discovery meta-analyses identified one region on chromosome 15q25.1 meeting genome-wide significance in ever smokers that includes AGPHD1, IREB2, and CHRNA5/CHRNA3 genes. The region was also modestly associated among never smokers. Gene expression studies confirmed the presence of CHRNA5/3 in lung, airway smooth muscle, and bronchial epithelial cells. A single-nucleotide polymorphism in HTR4, a gene previously related to FEV1/FVC, achieved genome-wide statistical significance in combined meta-analysis. Top single-nucleotide polymorphisms in ADAM19, RARB, PPAP2B, and ADAMTS19 were nominally replicated in the COPD meta-analysis. Conclusions: These results suggest an important role for the CHRNA5/3 region as a genetic risk factor for airflow obstruction that may be independent of smoking and implicate the HTR4 gene in the etiology of airflow obstruction. C1 [Wilk, Jemma B.] Brigham & Womens Hosp, Div Aging, Dept Med, Boston, MA 02120 USA. [Wilk, Jemma B.; Cho, Michael H.; Litonjua, Augusto; Silverman, Edwin K.] Harvard Univ, Sch Med, Boston, MA USA. [Wilk, Jemma B.; Dupuis, Josee; O'Connor, George T.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Shrine, Nick R. G.; Artigas, Maria Soler; Tobin, Martin D.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England. [Shrine, Nick R. G.; Artigas, Maria Soler; Tobin, Martin D.] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England. [Loehr, Laura R.; Franceschini, Nora; North, Kari E.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Zhao, Jing Hua; Wareham, Nicholas J.; Loos, Ruth J. F.] Addenbrookes Hosp, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England. [Manichaikul, Ani; Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Manichaikul, Ani] Univ Virginia, Dept Publ Hlth Sci, Div Biostat & Epidemiol, Charlottesville, VA USA. [Lopez, Lorna M.; Davies, Gail; Starr, John M.; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland. [Lopez, Lorna M.; Davies, Gail; Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland. [Smith, Albert Vernon; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland. [Smith, Albert Vernon; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland. [Heckbert, Susan R.; Marciante, Kristin D.; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Smolonska, Joanna; Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. [Tang, Wenbo; Cassano, Patricia A.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. [Loth, Daan W.; Hofman, Albert; Lahousse, Lies; Rivadeneira, Fernando; Uitterlinden, Andre G.; Stricker, Bruno H.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Loth, Daan W.; Stricker, Bruno H.] Inspectorate Healthcare, The Hague, Netherlands. [Curjuric, Ivan; Imboden, Medea; Probst-Hensch, Nicole] Swiss Trop & Publ Hlth Inst SwissTPH, Basel, Switzerland. [Curjuric, Ivan; Imboden, Medea; Probst-Hensch, Nicole] Univ Basel, Basel, Switzerland. [Hui, Jennie; James, Alan L.; Musk, Arthur W.] Sir Charles Gairdner Hosp, Busselton Populat Med Res Inst, Nedlands, WA 6009, Australia. [Hui, Jennie] QEII Med Ctr, PathW Lab Med Western Australia, Nedlands, WA, Australia. [Hui, Jennie] Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia. [Hui, Jennie; Musk, Arthur W.] Univ Western Australia, Sch Populat Hlth, Nedlands, WA 6009, Australia. [Cho, Michael H.; Litonjua, Augusto; Silverman, Edwin K.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02120 USA. [Cho, Michael H.; Litonjua, Augusto; Silverman, Edwin K.] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02120 USA. [Latourelle, Jeanne C.; Myers, Richard H.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Henry, Amanda P.; Hall, Ian P.] Univ Nottingham, Div Therapeut & Mol Med, Nottingham NG7 2RD, England. [Aldrich, Melinda] Vanderbilt Univ, Med Ctr, Dept Thorac Surg, Nashville, TN USA. [Aldrich, Melinda] Vanderbilt Univ, Med Ctr, Div Epidemiol, Nashville, TN USA. [Bakke, Per; Gulsvik, Amund] Univ Bergen, Haukeland Univ Hosp, Dept Thorac Med, Bergen, Norway. [Bakke, Per; Gulsvik, Amund] Univ Bergen, Inst Med, Bergen, Norway. [Beaty, Terri H.] Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. [Bentley, Amy R.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. [Borecki, Ingrid B.; Province, Michael A.] Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA. [Brusselle, Guy G.; Lahousse, Lies] Ghent Univ Hosp, Dept Resp Med, Ghent, Belgium. [Burkart, Kristin M.; Barr, R. Graham] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. [Chen, Ting-hsu] Vet Adm Boston Healthcare Syst, Dept Med, Pulm & Crit Care Med Sect, Boston, MA USA. [Chen, Ting-hsu; O'Connor, George T.] Boston Univ, Sch Med, Dept Med, Sect Pulm Allergy & Crit Care Med, Boston, MA 02118 USA. [Couper, David] Univ N Carolina, Dept Biostat, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Crapo, James D.] Natl Jewish Hlth, Denver, CO USA. [Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Hancock, Dana B.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA. [Hancock, Dana B.] Res Triangle Inst Int, Behav Hlth Epidemiol Program, Res Triangle Pk, NC USA. [Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. [Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.; Stricker, Bruno H.] NCHA, NGI, Leiden, Netherlands. [James, Alan L.] Sir Charles Gairdner Hosp, Dept Pulm Physiol & Sleep Med, Nedlands, WA 6009, Australia. [James, Alan L.; Musk, Arthur W.] Univ Western Australia, Sch Med & Pharmacol, Nedlands, WA 6009, Australia. [Khaw, Kay-Tee] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Liu, Yongmei] Wake Forest Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC USA. [Lohman, Kurt K.] Wake Forest Sch Med, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC USA. [Lomas, David A.] Univ Cambridge, Cambridge Inst Med Res, Cambridge, England. [Lumley, Thomas] Univ Auckland, Dept Stat, Auckland 1, New Zealand. [McArdle, Wendy L.] Univ Bristol, ALSPAC Lab, Sch Social & Community Med, Bristol, Avon, England. [Meibohm, Bernd] Univ Tennessee, Ctr Hlth Sci, Coll Pharm, Memphis, TN 38163 USA. [Morrison, Alanna C.] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX USA. [Musk, Arthur W.] Sir Charles Gairdner Hosp, Dept Resp Med, Nedlands, WA 6009, Australia. [Postma, Dirkje S.] Univ Groningen, Univ Med Ctr Groningen, Dept Pulmonol, Groningen, Netherlands. [Postma, Dirkje S.; Boezen, H. Marike] Univ Groningen, Univ Med Ctr Groningen, Groningen Res Inst Asthma, Groningen, Netherlands. [Postma, Dirkje S.; Boezen, H. Marike] Univ Groningen, Univ Med Ctr Groningen, COPD, Groningen, Netherlands. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Unit, Seattle, WA USA. [Rivadeneira, Fernando; Uitterlinden, Andre G.; Stricker, Bruno H.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands. [Rochat, Thierry] Univ Hosp Geneva, Div Pulm Med, Geneva, Switzerland. [Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Starr, John M.] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland. [Zanen, Pieter] Univ Med Ctr Utrecht, Div Heart & Lungs, Utrecht, Netherlands. [Palmer, Lyle J.] Ontario Inst Canc Res, Toronto, ON, Canada. [Palmer, Lyle J.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada. [Cassano, Patricia A.] Weill Cornell Med Coll, Dept Publ Hlth, New York, NY USA. [Barr, R. Graham] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Strachan, David P.] Univ London, Div Populat Hlth Sci & Educ, London, England. [Boezen, H. Marike] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands. [Gharib, Sina A.] Univ Washington, Dept Med, Div Pulm & Crit Care Med, Ctr Lung Biol, Seattle, WA USA. [Stricker, Bruno H.] Erasmus MC, Dept Med Informat, Rotterdam, Netherlands. RP Wilk, JB (reprint author), Brigham & Womens Hosp, Div Aging, Dept Med, 1620 Tremont St,3rd Floor, Boston, MA 02120 USA. EM jwilk@rics.bwh.harvard.edu RI Deary, Ian/C-6297-2009; Wijmenga, Cisca/D-2173-2009; Palmer, Lyle/K-3196-2014; Gudnason, Vilmundur/K-6885-2015; Rivadeneira, Fernando/O-5385-2015; Soler Artigas, Maria/L-6529-2013; Smith, Albert/K-5150-2015; OI Shrine, Nick/0000-0003-3641-4371; Manichaikul, Ani/0000-0002-5998-795X; Hancock, Dana/0000-0003-2240-3604; Dupuis, Josee/0000-0003-2871-3603; Wijmenga, Cisca/0000-0002-5635-1614; Hall, Ian/0000-0001-9933-3216; Lahousse, Lies/0000-0002-3494-4363; London, Stephanie/0000-0003-4911-5290; Litonjua, Augusto/0000-0003-0422-5875; Palmer, Lyle/0000-0002-1628-3055; Gudnason, Vilmundur/0000-0001-5696-0084; Rivadeneira, Fernando/0000-0001-9435-9441; Soler Artigas, Maria/0000-0002-3213-1107; Smith, Albert/0000-0003-1942-5845; O'Connor, George/0000-0002-6476-3926; Latourelle, Jeanne/0000-0002-4218-9572; Myers, Richard/0000-0002-8365-2674 FU Flight Attendant Medical Research Institute; NHLBI's Framingham Heart Study [N01-HC-25195]; Affymetrix, Inc. [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center; National Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694]; National Human Genome Research Institute [U01HG004402]; National Institutes of Health [HHSN268200625226C, UL1RR025005]; NIH Roadmap for Medical Research; Division of Intramural Research, National Institute of Environmental Health [ZO1 ES43012]; NHLBI [N01-HC-85239, N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HL080295, HL075366, HL087652, HL105756, N01HR76101, N01HR76102]; National Institute of Neurological Disorders and Stroke; National Institute on Aging (NIA) [AG-023629, AG-15928, AG-20098, AG-027058]; Cedars-Sinai Board of Govemors' Chair in Medical Genetics; National Center for Research Resources CTSI grant [UL 1RR033176]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]; European Union [201379]; Medical Research Council [G0000934]; Wellcome Trust [068545/Z/02, 076113/B104/Z]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases, National Human Genome Research Institute, National Institute of Child Health and Human Development; Juvenile Diabetes Research Foundation International (IDRFI); JDRFI; National Institute for Health Research Cambridge Biomedical Research Centre; European Commission Framework Program 6 [018996]; French Ministry of Research; Cancer Research UK; Medical Research Council; NIH [N01-AG-12100]; NIA Intramural Research Program; Hjartavernd (the Icelandic Heart Association),; Althingi (the Icelandic Parliament); Swiss National Science Foundation [33CS30-134276/1, 33CSCO-108796, 3247BO-104283, 3247BO-104288, 3247BO-104284, 3247-065896, 3100-059302, 3200-052720, 3200-042532, 4026-028099, 3233-054996, PDFMP3-12317I]; Federal Office for Forest, Environment, and Landscape; Federal Office of Public Health; Federal Office of Roads and Transport; canton's government of Aargau, Basel-Stadt, Basel-Land, Geneva, Luzern; Ticino, Valais, Zurich, the Swiss Lung League, the canton's Lung League of Basel Stadt/Basel Landschaft, Geneva, Ticin; Valais and Zurich, Schweizerische Unfallversicherungsanstalt (SUVA), Freiwillige Akademische Gesellschaft, UBS Wealth Foundation; Talecris Biotherapeutics GmbH; Abbott Diagnostics; Healthways, Western Australia; Great Wine Estates of the Margaret River region of Western Australia; AXA Research Fund; Biotechnology and Biological Sciences Research Council (BBSRC) [BB/F019394/1]; Research Into Ageing [LBC1936]; Age UK (Disconnected Mind; cross council Lifelong Health and Wellbeing Initiative [G0700704/84698]; BBSRC; Engineering and Physical Sciences Research Council; Economic and Social Research Council; Medical Research Council (MRC); U.S. NIH [R01 HL075478, R01 HL084323, P01 HL083069, 1101 HL089856, K12HL089990, K08 HL097029, U01 HL089897]; Centers for Medicare and Medicaid Services; Agency for Healthcare Research and Quality; Cooperative Studies Program/ERIC of the U.S. Department of Veterans Affairs; GlaxoSmithKline; COPD Foundation; Intramural Research Programs of the NIH, the National Institute of Environmental Health Sciences [Z01ES043012]; CHARGE Consortium; U.K. MRC Senior Clinical Fellowship [G0902313]; MRC [G1000861]; [U01 DK062418]; [N01HR76103]; [N01HR76104]; [N01HR76105]; [N01HR76106]; [N01HR76107]; [N01HR76108]; [N01HR76109]; [N01 HR76110]; [N01HR76111]; [N01HR76112]; [N01HR76113]; [N01HR76114]; [N01HR76115]; [N01HR76116]; [N01HR76118]; [N01HR76119] FX J.B.W. is supported by a Young Clinical Scientist Award from the Flight Attendant Medical Research Institute. Research was conducted in part using data and resources from the Framingham Heart Study of the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) and Boston University School of Medicine. The analyses reflect intellectual input and resource development from the Framingham investigators participating in the SNP Health Association Resource (SHARe) project. This work was partially supported by the NHLBI's Framingham Heart Study (contract N01-HC-25195) and its contract with Affymetrix, Inc. for genotyping services (contract N02-HL-6-4278). A portion of this research used the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center.; The Atherosclerosis Risk in Communities Study is performed as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. Infrastructure was partly supported by grant number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. Work was supported in part by the Division of Intramural Research, National Institute of Environmental Health Sciences ZO1 ES43012.; This CHS research was supported by NHLBI contracts N01-HC-85239, N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133 and NHLBI grants HL080295, HL075366, HL087652, HL105756 with additional contribution from National Institute of Neurological Disorders and Stroke. Additional support was provided through AG-023629, AG-15928, AG-20098, and AG-027058 from the National Institute on Aging (NIA) and the Cedars-Sinai Board of Govemors' Chair in Medical Genetics (P.R.). DNA handling and genotyping was supported in part by National Center for Research Resources CTSI grant UL 1RR033176 and National Institute of Diabetes and Digestive and Kidney Diseases grant DK063491 to the Southern California Diabetes Endocrinology Research Center.; COPACETIC (i.e., COPD Pathology: Addressing Critical gaps, Early Treatment and diagnosis and Innovative Concepts) is funded by the European Union FP7 program, grant agreement number 201379.; We acknowledge use of phenotype and genotype data from the British 1958 Birth Cohort DNA collection, funded by the Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02. (http://www.b58cgene.sgul.ac.uk/). Genotyping for the B58C-VVTCCC subset was funded by the Wellcome Trust grant 076113/B104/Z. The B58C-T1DGC genotyping used resources provided by the Type 1 Diabetes Genetics Consortium, a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Allergy and Infectious Diseases, National Human Genome Research Institute, National Institute of Child Health and Human Development, and Juvenile Diabetes Research Foundation International (IDRFI) and supported by U01 DK062418. B58C-T1DGC GWAS data were deposited by the Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research (CIMR), University of Cambridge, which is funded by JDRFI, the Wellcome Trust, and the National Institute for Health Research Cambridge Biomedical Research Centre; the CIMR is in receipt of a Wellcome Trust Strategic Award (079895). The B58C-GABRIEL genotyping was supported by a contract from the European Commission Framework Program 6 (018996) and grants from the French Ministry of Research.; The EPIC-Norfolk is supported by research program grant funding from Cancer Research UK and the Medical Research Council.; The AGES-Reykjavik Study is funded by NIH contract N01-AG-12100, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament).; The Health, Aging, and Body Composition Study was supported by NIA contracts N01AG62101, N01AG2103, and N01AG62106 and in part by the Intramural Research Program of the NIA, NIH. The genome-wide association study was funded by NIA grant 1R01AG032098-01A1 to Wake Forest Health Sciences, and genotyping services were provided by the Center for Inherited Disease Research, which is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C. This research was further supported by RC1AG035835.; The Rotterdam Studies were funded by the Netherlands Organization of Scientific Research NWO Investments, nr. 175.010.2005.011, 911-03-012, Research Institute for Diseases in the Elderly, 014-93-015; RIDE2, the Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) project nr. 050-060-810, the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII) Municipality of Rotterdam.; SAPALDIA was supported by the Swiss National Science Foundation (grants no 33CS30-134276/1, 33CSCO-108796, 3247BO-104283, 3247BO-104288, 3247BO-104284, 3247-065896, 3100-059302, 3200-052720, 3200-042532, 4026-028099, 3233-054996, PDFMP3-12317I), the Federal Office for Forest, Environment, and Landscape, the Federal Office of Public Health, the Federal Office of Roads and Transport, the canton's government of Aargau, Basel-Stadt, Basel-Land, Geneva, Luzern, Ticino, Valais, Zurich, the Swiss Lung League, the canton's Lung League of Basel Stadt/Basel Landschaft, Geneva, Ticino, Valais and Zurich, Schweizerische Unfallversicherungsanstalt (SUVA), Freiwillige Akademische Gesellschaft, UBS Wealth Foundation, Talecris Biotherapeutics GmbH, Abbott Diagnostics. Genotyping in the GABRIEL framework was supported by grants European Commission 018996 and Wellcome Trust WT 084703MA.; The 1994 Busse Iton follow-up Health Study was supported by Healthways, Western Australia. The Busse Iton Health Study is supported by The Great Wine Estates of the Margaret River region of Western Australia. The study gratefully acknowledges the assistance of the Western Australian DNA Bank (NHMRC Enabling Facility) with DNA samples and the support provided by The Ark at University of Western Australia for this study.; L.M.L. is the beneficiary of a postdoctoral grant from the AXA Research Fund. The Lothian Birth Cohort 1936 (LBC1936) whole genome association study was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) (ref. BB/F019394/1). The LBC1936 research was initially supported by a program grant from Research Into Ageing (ref. 251) and continues with program grants from Age UK (Disconnected Mind). The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (ref. G0700704/84698). Funding from the BBSRC, Engineering and Physical Sciences Research Council, Economic and Social Research Council, and Medical Research Council (MRC) is gratefully acknowledged.; The COPD cohorts meta-analysis was supported by U.S. NIH grants R01 HL075478, R01 HL084323, P01 HL083069, 1101 HL089856 (E.K.S.); K12HL089990 and K08 HL097029 (M.H.C); and U01 HL089897 (J.D.C.). The National Emphysema Treatment Trial was supported by the National Heart, Lung, and Blood Institute, the Centers for Medicare and Medicaid Services, and the Agency for Healthcare Research and Quality. The National Emphysema Treatment Trial was supported by NHLBI contracts N01HR76101, N01HR76102, N01HR76103, N01HR76104, N01HR76105, N01HR76106, N01HR76107, N01HR76108, N01HR76109, N01 HR76110, N01HR76111, N01HR76112, N01HR76113, N01HR76114, N01HR76115, N01HR76116, N01HR76118, and N01HR76119. The Normative Aging Study is supported by the Cooperative Studies Program/ERIC of the U.S. Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center. The Norway GenKOLS study (Genetics of Chronic Obstructive Lung Disease, GSK code RES11080) and the ECLIPSE study (clinicaltrials.gov identifier NCT00292552; GSK code SC0104960) are funded by GlaxoSmithKline. The COPDGene project is also supported by the COPD Foundation through contributions made to an Industry Advisory comprised of AstraZeneca, Boehringer Ingelheim, Novartis, and Sepracor.; This work was supported, in part, by Intramural Research Programs of the NIH, the National Institute of Environmental Health Sciences (Z01ES043012). The CHARGE Pulmonary Working Group acknowledges funding from the NHLBI (HL105756) and the CHARGE Consortium's organizational support.; Martin D. Tobin is supported by U.K. MRC Senior Clinical Fellowship G0902313. I.P.H. is supported by MRC (G1000861).; The Family Heart Study (FamHS) was supported by NIH grants R01-HL-087700 and R01-HL-088215 (MAP., PI) from NHLBI; and R01-DK-8925601 and R01DK-075681 (I.B.B, PI) from NIDDK.; MESA was supported by contracts N01-HC-95159 through N01-HC-95169 from the NHLBI and RR-024156. The MESA Lung study was supported by grants R01HL077612 and RC1-HL100543 from the NHLBI. Funding for SHARe genotyping was provided by NHLBI contract N02-HL-6-4278. NR 41 TC 68 Z9 70 U1 1 U2 20 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT 1 PY 2012 VL 186 IS 7 BP 622 EP 632 DI 10.1164/rccm.201202-0366OC PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 014NV UT WOS:000309383600013 PM 22837378 ER PT J AU Weaver, TE Mancini, C Maislin, G Cater, J Staley, B Landis, JR Ferguson, KA George, CFP Schulman, DA Greenberg, H Rapoport, DM Walsleben, JA Lee-Chiong, T Gurubhagavatula, I Kuna, ST AF Weaver, Terri E. Mancini, Cristina Maislin, Greg Cater, Jacqueline Staley, Bethany Landis, J. Richard Ferguson, Kathleen A. George, Charles F. P. Schulman, David A. Greenberg, Harly Rapoport, David M. Walsleben, Joyce A. Lee-Chiong, Teofilo Gurubhagavatula, Indira Kuna, Samuel T. TI Continuous Positive Airway Pressure Treatment of Sleepy Patients with Milder Obstructive Sleep Apnea Results of the CPAP Apnea Trial North American Program (CATNAP) Randomized Clinical Trial SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE continuous positive airway pressure; obstructive sleep apnea; daytime sleepiness; randomized clinical trial; functional status ID BREATHING DISORDERS; DAYTIME SLEEPINESS; PRACTICE PARAMETERS; PLACEBO; HEALTH; ADULTS; PERFORMANCE; POPULATION; MODAFINIL; THERAPY AB Rationale: Twenty-eight percent of people with mild to moderate obstructive sleep apnea experience daytime sleepiness, which interferes with daily functioning. It remains unclear whether treatment with continuous positive airway pressure improves daytime function in these patients. Objectives: To evaluate the efficacy of continuous positive airway pressure treatment to improve functional status in sleepy patients with mild and moderate obstructive sleep apnea. Methods: Patients with self-reported daytime sleepiness (Epworth Sleepiness Scale score >10) and an apnea-hypopnea index with 3% desaturation and from 5 to 30 events per hour were randomized to 8 weeks of active or sham continuous positive airway pressure treatment. After the 8-week intervention, participants in the sham arm received 8 weeks of active continuous positive airway pressure treatment. Measurements and Main Results: The Total score on the Functional Outcomes of Sleep Questionnaire was the primary outcome measure. intervention was 0.89 for the active group (n = 113) and 0.06 for the placebo group (n = 110) (P= 0.006). The group difference in mean change corresponded to an effect size of 0.41 (95% confidence interval, 0.14-0.67). The mean (SD) improvement in Functional Outcomes of Sleep Questionnaire Total score from the beginning to the end of the crossover phase (n = 91) was 1.73 +/- 2.50 (t[90] = 6.59; P < 0.00001) with an effect size of 0.69. Conclusions: Continuous positive airway pressure treatment improves the functional outcome of sleepy patients with mild and moderate obstructive sleep apnea. Clinical trial registered with www.clinicaltrials.gov (NCT 00127348). C1 [Weaver, Terri E.] Univ Illinois, Coll Nursing, Dept Biobehav Hlth Sci, Chicago, IL 60612 USA. [Weaver, Terri E.; Mancini, Cristina] Univ Penn, Sch Nursing, Biobehav & Hlth Sci Div, Philadelphia, PA 19104 USA. [Weaver, Terri E.; Maislin, Greg; Cater, Jacqueline; Staley, Bethany; Gurubhagavatula, Indira; Kuna, Samuel T.] Univ Penn, Sch Med, Ctr Sleep & Circadian Neurobiol, Div Sleep Med,Dept Med, Philadelphia, PA 19104 USA. [Maislin, Greg; Cater, Jacqueline] Biostat Consulting, Wynnewood, PA USA. [Landis, J. Richard] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Ferguson, Kathleen A.; George, Charles F. P.] Univ Western Ontario, Schulich Sch Med & Dent, Div Respirol, London, ON, Canada. [Schulman, David A.] Emory Univ, Emory Univ Hosp, Div Pulm Allergy & Crit Care Med, Atlanta, GA 30322 USA. [Greenberg, Harly] N Shore Long Isl Jewish Hlth Syst, Div Pulm Crit Care & Sleep Med, New Hyde Pk, NY USA. [Rapoport, David M.; Walsleben, Joyce A.] NYU, Sleep Disorder Ctr, Sch Med, Dept Med,Div Pulm & Crit Care & Sleep Med, New York, NY USA. [Lee-Chiong, Teofilo] Natl Jewish Hlth, Dept Med, Denver, CO USA. [Kuna, Samuel T.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Weaver, TE (reprint author), Univ Illinois, Coll Nursing, Dept Biobehav Hlth Sci, 845 S Damen Ave MC 802, Chicago, IL 60612 USA. EM teweaver@uic.edu OI Rapoport, David/0000-0002-4855-2600 FU National Institutes for Health National Heart, Lung, and Blood Institute [R01 HL076101]; Sleep Medicine Education and Research Foundation (American Academy of Sleep Medicine); Respironics Sleep and Respiratory Research Foundation; Cephalon, Inc. FX Supported by National Institutes for Health National Heart, Lung, and Blood Institute, R01 HL076101 (T.E.W., C.M., B.S., J.R.L., K.A.F., C.F.P.G., D.A.S., H.G., D.M.R., JAW., S.T.K.); Sleep Medicine Education and Research Foundation (American Academy of Sleep Medicine) (T.E.W.); Respironics Sleep and Respiratory Research Foundation (T.E.W.); and Cephalon, Inc. (T.E.W., CM.). Equipment provided by Philips Respironics, Inc., ProTech Services, Inc., and Embla. NR 32 TC 66 Z9 67 U1 1 U2 7 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT 1 PY 2012 VL 186 IS 7 BP 677 EP 683 DI 10.1164/rccm.201202-0200OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 014NV UT WOS:000309383600019 PM 22837377 ER PT J AU Abecassis, M Bridges, ND Clancy, CJ Dew, MA Eldadah, B Englesbe, MJ Flessner, MF Frank, JC Friedewald, J Gill, J Gries, C Halter, JB Hartmann, EL Hazzard, WR Horne, FM Hosenpud, J Jacobson, P Kasiske, BL Lake, J Loomba, R Malani, PN Moore, TM Murray, A Nguyen, MH Powe, NR Reese, PP Reynolds, H Samaniego, MD Schmader, KE Segev, DL Shah, AS Singer, LG Sosa, JA Stewart, ZA Tan, JC Williams, WW Zaas, DW High, KP AF Abecassis, M. Bridges, N. D. Clancy, C. J. Dew, M. A. Eldadah, B. Englesbe, M. J. Flessner, M. F. Frank, J. C. Friedewald, J. Gill, J. Gries, C. Halter, J. B. Hartmann, E. L. Hazzard, W. R. Horne, F. M. Hosenpud, J. Jacobson, P. Kasiske, B. L. Lake, J. Loomba, R. Malani, P. N. Moore, T. M. Murray, A. Nguyen, M. -H. Powe, N. R. Reese, P. P. Reynolds, H. Samaniego, M. D. Schmader, K. E. Segev, D. L. Shah, A. S. Singer, L. G. Sosa, J. A. Stewart, Z. A. Tan, J. C. Williams, W. W. Zaas, D. W. High, K. P. TI Solid-Organ Transplantation in Older Adults: Current Status and Future Research SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Review DE Aging; elderly; heart; kidney; liver; lung; transplantation ID QUALITY-OF-LIFE; LIVING KIDNEY DONORS; RENAL-TRANSPLANTATION; LONG-TERM; LIVER-TRANSPLANTATION; HEART-TRANSPLANTATION; LUNG TRANSPLANTATION; COGNITIVE IMPAIRMENT; ELDERLY-PATIENTS; ALLOGRAFT SURVIVAL AB An increasing number of patients older than 65 years are referred for and have access to organ transplantation, and an increasing number of older adults are donating organs. Although short-term outcomes are similar in older versus younger transplant recipients, older donor or recipient age is associated with inferior long-term outcomes. However, age is often a proxy for other factors that might predict poor outcomes more strongly and better identify patients at risk for adverse events. Approaches to transplantation in older adults vary across programs, but despite recent gains in access and the increased use of marginal organs, older patients remain less likely than other groups to receive a transplant, and those who do are highly selected. Moreover, few studies have addressed geriatric issues in transplant patient selection or management, or the implications on health span and disability when patients age to late life with a transplanted organ. This paper summarizes a recent trans-disciplinary workshop held by ASP, in collaboration with NHLBI, NIA, NIAID, NIDDK and AGS, to address issues related to kidney, liver, lung, or heart transplantation in older adults and to propose a research agenda in these areas. C1 [High, K. P.] Wake Forest Sch Med, Winston Salem, NC USA. [Abecassis, M.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA. [Abecassis, M.] Northwestern Univ, Feinberg Sch Med, Dept Microbiol Immunol, Chicago, IL 60611 USA. [Bridges, N. D.] NIAID, Transplantat Immunobiol Branch, Bethesda, MD 20892 USA. [Bridges, N. D.] NIAID, Clin Transplantat Sect, Bethesda, MD 20892 USA. [Dew, M. A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Eldadah, B.] NIA, Div Geriatr & Clin Gerontol, Bethesda, MD 20892 USA. [Englesbe, M. J.] Univ Michigan, Sch Med, Dept Surg, Div Transplantat, Ann Arbor, MI USA. [Flessner, M. F.] NIDDK, Div Kidney Urol & Hematol Dis, Bethesda, MD USA. [Frank, J. C.] Univ Calif Los Angeles, Geffen Sch Med, Los Angeles, CA USA. [Friedewald, J.] Northwestern Univ, Dept Med, Chicago, IL 60611 USA. [Gill, J.] Univ British Columbia, Div Nephrol, Vancouver, BC V5Z 1M9, Canada. [Gries, C.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Halter, J. B.] Univ Michigan, Sch Med, Div Geriatr & Palliat Med, Ann Arbor, MI USA. [Hartmann, E. L.] Piedmont Transplant Inst, Atlanta, GA USA. [Hazzard, W. R.] Univ Washington, Div Gerontol & Geriatr Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Horne, F. M.] Assoc Specialty Prof, Alexandria, VA USA. [Hosenpud, J.] Mayo Clin, Dept Heart Transplant, Jacksonville, FL 32224 USA. [Jacobson, P.] Univ Minnesota, Dept Expt & Clin Pharmacol, Minneapolis, MN USA. [Kasiske, B. L.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Lake, J.] Univ Minnesota, Liver Transplant Program, Minneapolis, MN USA. [Loomba, R.] Univ Calif San Diego, San Diego Sch Med, San Diego, CA 92103 USA. [Malani, P. N.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. [Moore, T. M.; Reynolds, H.] NHLBI, Bethesda, MD 20892 USA. [Murray, A.] Univ Minnesota, Div Geriatr, Minneapolis, MN USA. [Powe, N. R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Reese, P. P.] Univ Penn, Philadelphia, PA 19104 USA. [Schmader, K. E.] Duke Univ, Sch Med, GRECC, Durham VA Med Ctr, Durham, NC USA. [Schmader, K. E.] Duke Univ, Sch Med, Div Geriatr Med, Durham, NC USA. [Segev, D. L.] Johns Hopkins Univ, Sch Med, Div Transplant Surg, Baltimore, MD USA. [Shah, A. S.] Johns Hopkins Univ, Sch Med, Div Cardiac Surg, Baltimore, MD USA. [Singer, L. G.] Univ Toronto, Toronto Lung Transplant Program, Toronto, ON, Canada. [Sosa, J. A.] Yale Univ, Sch Med, Dept Surg, Div Endocrine Surg, New Haven, CT 06510 USA. [Sosa, J. A.] Yale Univ, Sch Med, Dept Surg, Div Surg Oncol, New Haven, CT 06510 USA. [Stewart, Z. A.] Univ Iowa, Carver Coll Med, Iowa City, IA USA. [Tan, J. C.] Stanford Univ, Adult Kidney & Pancreas Transplant Program, Palo Alto, CA 94304 USA. [Williams, W. W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zaas, D. W.] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA. RP High, KP (reprint author), Wake Forest Sch Med, Winston Salem, NC USA. EM khigh@wakehealth.edu OI Englesbe, Michael/0000-0001-8691-9111; Shah, Ashish/0000-0002-1821-9110; Friedewald, John/0000-0002-9344-9928 FU National Institute on Aging [1 U13 AG040938-01]; John A. Hartford Foundation FX This workshop was supported by generous grants to ASP from the National Institute on Aging (1 U13 AG040938-01) and the John A. Hartford Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIA or the National Institutes of Health. In addition, the views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention by trade names, commercial practices, or organizations imply endorsement by the U.S. Government. NR 138 TC 38 Z9 38 U1 1 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD OCT PY 2012 VL 12 IS 10 BP 2608 EP 2622 DI 10.1111/j.1600-6143.2012.04245.x PG 15 WC Surgery; Transplantation SC Surgery; Transplantation GA 011QN UT WOS:000309180000009 PM 22958872 ER PT J AU Li, L Khatri, P Sigdel, TK Tran, T Ying, L Vitalone, MJ Chen, A Hsieh, S Dai, H Zhang, M Naesens, M Zarkhin, V Sansanwal, P Chen, R Mindrinos, M Xiao, W Benfield, M Ettenger, RB Dharnidharka, V Mathias, R Portale, A McDonald, R Harmon, W Kershaw, D Vehaskari, VM Kamil, E Baluarte, HJ Warady, B Davis, R Butte, AJ Salvatierra, O Sarwal, MM AF Li, L. Khatri, P. Sigdel, T. K. Tran, T. Ying, L. Vitalone, M. J. Chen, A. Hsieh, S. Dai, H. Zhang, M. Naesens, M. Zarkhin, V. Sansanwal, P. Chen, R. Mindrinos, M. Xiao, W. Benfield, M. Ettenger, R. B. Dharnidharka, V. Mathias, R. Portale, A. McDonald, R. Harmon, W. Kershaw, D. Vehaskari, V. M. Kamil, E. Baluarte, H. J. Warady, B. Davis, R. Butte, A. J. Salvatierra, O. Sarwal, M. M. TI A Peripheral Blood Diagnostic Test for Acute Rejection in Renal Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Acute allograft rejection; biomarker; bioinformatics; renal allograft rejection; renal transplantation; transplantation; transplantation genomics; transplant rejection; translational research ID ANTIBODY-MEDIATED REJECTION; REGULATORY T-CELLS; ALLOGRAFT-REJECTION; LOGISTIC-REGRESSION; INFLAMMATION; RECRUITMENT; DYSFUNCTION; MONOCYTES; INJURY AB Monitoring of renal graft status through peripheral blood (PB) rather than invasive biopsy is important as it will lessen the risk of infection and other stresses, while reducing the costs of rejection diagnosis. Blood gene biomarker panels were discovered by microarrays at a single center and subsequently validated and cross-validated by QPCR in the NIH SNSO1 randomized study from 12 US pediatric transplant programs. A total of 367 unique human PB samples, each paired with a graft biopsy for centralized, blinded phenotype classification, were analyzed (115 acute rejection (AR), 180 stable and 72 other causes of graft injury). Of the differentially expressed genes by microarray, Q-PCR analysis of a five gene-set (DUSP1, PBEF1, PSEN1, MAPK9 and NKTR) classified AR with high accuracy. A logistic regression model was built on independent training-set (n = 47) and validated on independent test-set (n = 198)samples, discriminating AR from STA with 91% sensitivity and 94% specificity and AR from all other non-AR phenotypes with 91% sensitivity and 90% specificity. The 5-gene set can diagnose AR potentially avoiding the need for invasive renal biopsy. These data support the conduct of a prospective study to validate the clinical predictive utility of this diagnostic tool. C1 [Li, L.; Sigdel, T. K.; Tran, T.; Vitalone, M. J.; Hsieh, S.; Dai, H.; Sansanwal, P.; Sarwal, M. M.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94115 USA. [Li, L.; Khatri, P.; Sigdel, T. K.; Tran, T.; Ying, L.; Vitalone, M. J.; Chen, A.; Hsieh, S.; Dai, H.; Zhang, M.; Naesens, M.; Zarkhin, V.; Chen, R.; Butte, A. J.; Salvatierra, O.; Sarwal, M. M.] Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. [Salvatierra, O.] Stanford Univ, Dept Surg, Stanford, CA 94305 USA. [Mindrinos, M.; Davis, R.] Stanford Univ, Dept Biochem, Stanford, CA 94305 USA. [Xiao, W.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Benfield, M.] Univ Alabama Birmingham, Birmingham, AL USA. [Ettenger, R. B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Div Nephrol,UCLA Childrens Hlth Ctr, Los Angeles, CA 90024 USA. [Dharnidharka, V.] Univ Florida, Coll Med, Dept Pediat Nephrol, Gainesville, FL USA. [Dharnidharka, V.] Shands Childrens Hosp, Gainesville, FL USA. [Mathias, R.] Nemours Childrens Clin, Orlando, FL USA. [Portale, A.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA. [McDonald, R.] Childrens Hosp & Reg Med Ctr, Seattle, WA USA. [Harmon, W.] Harvard Univ, Dept Pediat, Cambridge, MA 02138 USA. [Kershaw, D.] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. [Kamil, E.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Baluarte, H. J.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Warady, B.] Childrens Mercy Hosp, Kansas City, MO 64108 USA. RP Sarwal, MM (reprint author), Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94115 USA. EM sarwalm@cpmcri.org RI Naesens, Maarten/J-4766-2015; OI Naesens, Maarten/0000-0002-5625-0792; xiao, wenzhong/0000-0003-4944-6380 FU NIH [UO1AI055795, RO1AI061739]; ARRA within the Cooperative Clinical Trials in Pediatric Transplantation Consortium [3UO1 AI077821-0351]; Bristol Meyers Squibb; Genentech; Astellas; Johnson Johnson; Genstruct; Lilly; Lilly and Tercica; Siemens FX We deeply appreciate the participation of patients at Stanford University and the NIH funded multicenter randomized study of steroid-avoidance versus steroid-based immunosuppression (SNSO1). We also are indebted to the support with patient recruitment and sample collections from transplant patients in the SNSO1 multicenter study centers. We thank Nancy Bridges and Daniel Rotrosen from NIH/NIAID for their continuous support and advice on the SNSO1 study. We thank Nikki Williams for the support throughout the manuscript preparation. The authors are grateful to Dr. Neeraja Kambham from Stanford University for her centralized, blinded reads of graft pathology and to Dr. Allan Kirk from Emory University for his support and suggestions to make the manuscript more meaningful. We are thankful to David Ikle, Michael Riggs, and Katie Poole in the validation phase of this project. Support from for this project was funded by NIH grants UO1AI055795 (OS awarded within the Cooperative Clinical Trials in Pediatric Transplantation Consortium), RO1AI061739 (MS), and ARRA funding 3UO1 AI077821-0351 (AK) awarded within the Cooperative Clinical Trials in Pediatric Transplantation Consortium.; Dr. Sarwal receives consulting and lecture fees from Bristol Meyers Squibb, Genentech and Astellas and has equity/ownership stock in Organ-I; Dr. Butte receives consulting fees from Johnson & Johnson, Genstruct, Lilly and Tercica, lecture fees from Siemens and Lilly and equity ownership/stock from Genstruct and NuMedii; Dr. Davis has equity ownership/stock in Affymetrix and Organ-I. VRD has received consulting fees from Bristol-Myers-Squibb and honoraria from Genzyme and Alexion. NR 33 TC 42 Z9 42 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD OCT PY 2012 VL 12 IS 10 BP 2710 EP 2718 DI 10.1111/j.1600-6143.2012.04253.x PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA 011QN UT WOS:000309180000018 PM 23009139 ER PT J AU Jonker, FHW Trimarchi, S Rampoldi, V Patel, HJ O'Gara, P Peterson, MD Fattori, R Moll, FL Voehringer, M Pyeritz, RE Hutchison, S Montgomery, D Isselbacher, EM Nienaber, CA Eagle, KA Gomes, WJ AF Jonker, Frederik H. W. Trimarchi, Santi Rampoldi, Vincenzo Patel, Himanshu J. O'Gara, Patrick Peterson, Mark D. Fattori, Rossella Moll, Frans L. Voehringer, Matthias Pyeritz, Reed E. Hutchison, Stuart Montgomery, Daniel Isselbacher, Eric M. Nienaber, Christoph A. Eagle, Kim A. Gomes, Walter J. CA Int Registry Acute Aortic TI Aortic Expansion After Acute Type B Aortic Dissection SO ANNALS OF THORACIC SURGERY LA English DT Article ID INTERNATIONAL REGISTRY; FALSE LUMEN; IRAD; ANEURYSMS; INSIGHTS; PREDICTORS; PROGNOSIS; DIAMETER; SURGERY; CM AB Background. A considerable number of patients with acute type B aortic dissection (ABAD) treated with medical management alone will exhibit aortic enlargement during follow-up, which could lead to aortic aneurysm and rupture. The purpose of this study was to investigate predictors of aortic expansion among ABAD patients enrolled in the International Registry of Acute Aortic Dissection. Methods. We analyzed 191 ABAD patients treated with medical therapy alone enrolled in the registry between 1996 and 2010, with available descending aortic diameter measurements at admission and during follow-up. The annual aortic expansion rate was calculated for all patients, and multivariate regression analysis was used to investigate factors affecting the expansion rate. Results. Aortic expansion was observed in 59% of ABAD patients; mean expansion rate was 1.7 +/- 7 mm/y. In multivariate analysis, white race (regression coefficient [RC], 4.6; 95% confidence interval [CI], 1.4 to 7.7) and an initial aortic diameter less than 4.0 cm (RC, 6.3; 95% CI, 4.0 to 8.6) were associated with increased aortic expansion. Female sex (RC, -3.8; 95% CI, -6.1 to -1.4), intramural hematoma (RC, -3.8; 95% CI, -6.5 to -1.1), and use of calcium-channel blockers (RC, -3.8; 95% CI, -6.2 to -1.3) were associated with decreased aortic expansion. Conclusions. White race and a small initial aortic diameter were associated with increased aortic expansion during follow-up, and decreased aortic expansion was observed among women, patients with intramural hematoma, and those on calcium-channel blockers. These data raise the possibility that the use of calcium-channel blockers after ABAD may reduce the rate of aortic expansion, and therefore further investigation is warranted. (Ann Thorac Surg 2012; 94: 1223-9) (C) 2012 by The Society of Thoracic Surgeons C1 [Jonker, Frederik H. W.] Maasstad Hosp Rotterdam, Dept Surg, NL-3011 AB Rotterdam, Netherlands. Policlin San Donato IRCCS, Milan, Italy. Univ Michigan Hlth Syst, Ann Arbor, MI USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Toronto, Toronto, ON, Canada. S Orsola Univ Hosp, Bologna, Italy. Univ Med Ctr Utrecht, Utrecht, Netherlands. Robert Bosch Krankenhaus, Stuttgart, Germany. Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. Univ Calgary, Calgary, AB, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Rostock, Rostock, Germany. [Gomes, Walter J.] Univ Fed Sao Paulo, Cardiovasc Surg Discipline, Escola Paulista Med, BR-04023900 Sao Paulo, Brazil. RP Jonker, FHW (reprint author), Maasstad Hosp Rotterdam, Dept Surg, Bulgersteyn 1C, NL-3011 AB Rotterdam, Netherlands. EM jonkerf@maasstadziekenhuis.nl; wjgomes.dcir@epm.br RI Trimarchi, Santi/J-7361-2016 OI Trimarchi, Santi/0000-0001-5996-3264 FU University of Michigan Health System; Varbedian Fund for Aortic Research; Mardigian Foundation; Gore Medical Inc (Flagstaff, AZ) FX The IRAD is supported by grants from the University of Michigan Health System, the Varbedian Fund for Aortic Research, the Mardigian Foundation, and Gore Medical Inc (Flagstaff, AZ). NR 26 TC 25 Z9 25 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD OCT PY 2012 VL 94 IS 4 BP 1223 EP 1229 DI 10.1016/j.athoracsur.2012.05.040 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 016OJ UT WOS:000309528300037 PM 22776085 ER PT J AU Lipsky, LM Nansel, TR Haynie, DL Mehta, SN Laffel, LMB AF Lipsky, L. M. Nansel, T. R. Haynie, D. L. Mehta, S. N. Laffel, L. M. B. TI Associations of food preferences and household food availability with dietary intake and quality in youth with type 1 diabetes SO APPETITE LA English DT Article DE Preference; Availability; Dietary intake; Dietary quality; Youth; Type 1 Diabetes ID VEGETABLE CONSUMPTION; HOME AVAILABILITY; PROJECT EAT; FRUIT; ADOLESCENTS; CHILDREN; JUICE; VALIDITY; BEHAVIOR; SCHOOLCHILDREN AB The objective of this study was to examine associations of food preferences and availability with dietary intake in youth with type 1 diabetes, for whom dietary intake and quality are essential to disease management. Youth (n = 252, age 13.2 +/- 2.8 y, diabetes duration 6.3 +/- 3.4 y) reported preferences and parents reported household availability for 61 food items categorized as fruit, vegetables, whole grains, refined grains and fats/sweets. Youth energy-adjusted daily servings of food groups, Healthy Eating Index-2005 and Nutrient Rich Foods 9.3 scores were calculated from 3-day diet records. Associations of dietary intake and quality variables with preference and availability of all food groups were evaluated by linear regressions adjusted for sociodemographic characteristics. Fruit and whole grain intake were positively related to corresponding preference and availability; whole grain intake and refined grain availability were inversely related. Vegetable, refined grain and fats/sweets intake were unrelated to preference and availability. Diet quality measures were related positively to fruit preference and whole grain availability and inversely to refined grains availability. Findings indicate associations of dietary intake with food preference and availability vary by food group in youth with type 1 diabetes. Measures of overall dietary quality were more consistently associated with food group availability than preferences. Published by Elsevier Ltd. C1 [Lipsky, L. M.; Nansel, T. R.; Haynie, D. L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Mehta, S. N.; Laffel, L. M. B.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Genet & Epidemiol,Pediat Adolescent & Young, Boston, MA 02215 USA. RP Lipsky, LM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, NIH, Dept Hlth & Human Serv, 6100 Execut Blvd,Suite 7B13, Rockville, MD 20852 USA. EM lipskylm@mail.nih.gov OI Nansel, Tonja/0000-0002-8298-7595; Haynie, Denise/0000-0002-8270-6079 FU National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development [HHSN267200703434C] FX This research was supported by the intramural research program of the National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Contract Number HHSN267200703434C. NR 46 TC 5 Z9 5 U1 0 U2 8 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0195-6663 EI 1095-8304 J9 APPETITE JI Appetite PD OCT PY 2012 VL 59 IS 2 BP 218 EP 223 DI 10.1016/j.appet.2012.05.005 PG 6 WC Behavioral Sciences; Nutrition & Dietetics SC Behavioral Sciences; Nutrition & Dietetics GA 013MR UT WOS:000309310000004 PM 22595289 ER PT J AU Byers, AL Vittinghoff, E Lui, LY Hoang, T Blazer, DG Covinsky, KE Ensrud, KE Cauley, JA Hillier, TA Fredman, L Yaffe, K AF Byers, Amy L. Vittinghoff, Eric Lui, Li-Yung Hoang, Tina Blazer, Dan G. Covinsky, Kenneth E. Ensrud, Kristine E. Cauley, Jane A. Hillier, Teresa A. Fredman, Lisa Yaffe, Kristine TI Twenty-Year Depressive Trajectories Among Older Women SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID LATE-LIFE DEPRESSION; NATIONAL-COMORBIDITY-SURVEY; PRIMARY-CARE PATIENTS; LATENT CLASS ANALYSIS; PHYSICAL-ACTIVITY; MAJOR DEPRESSION; COMMUNITY SAMPLE; FUTURE-RESEARCH; SYMPTOMS; ADULTS AB Context: Despite the frequent occurrence of depressive symptoms among older adults, especially women, little is known about the long-term course of late-life depressive symptoms. Objective: To characterize the natural course of depressive symptoms among older women (from the young old to the oldest old) followed up for almost 20 years. Design: Using latent-class growth-curve analysis, we analyzed women enrolled in an ongoing prospective cohort study (1988 through 2009). Setting: Clinic sites in Baltimore, Maryland; Minneapolis, Minnesota; the Monongahela Valley near Pittsburgh, Pennsylvania; and Portland, Oregon. Participants: We studied 7240 community-dwelling women 65 years or older. Main Outcome Measure: The Geriatric Depression Scale short form (score range, 0-15) was used to routinely assess depressive symptoms during the follow-up period. Results: Among older women, we identified 4 latent classes during 20 years, with the predicted probabilities of group membership totaling 27.8% with minimal depressive symptoms, 54.0% with persistently low depressive symptoms, 14.8% with increasing depressive symptoms, and 3.4% with persistently high depressive symptoms. In an adjusted model for latent class membership, odds ratios (ORs) for belonging in the increasing depressive symptoms and persistently high depressive symptoms classes, respectively, compared with a group having minimal depressive symptoms were substantially and significantly (P < .05) elevated for the following variables: baseline smoking (ORs, 4.69 and 7.97), physical inactivity (ORs, 2.11 and 2.78), small social network (ORs, 3.24 and 6.75), physical impairment (ORs, 8.11 and 16.43), myocardial infarction (ORs, 2.09 and 2.41), diabetes mellitus (ORs, 2.98 and 3.03), and obesity (ORs, 1.86 and 2.90). Conclusions: During 20 years, almost 20% of older women experienced persistently high depressive symptoms or increasing depressive symptoms. In addition, these women had more comorbidities, physical impairment, and negative lifestyle factors at baseline. These associations support the need for intervention and prevention strategies to reduce depressive symptoms into the oldest-old years. Arch Gen Psychiatry. 2012;69(10):1073-1079 C1 [Byers, Amy L.; Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Vittinghoff, Eric; Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Covinsky, Kenneth E.] Univ Calif San Francisco, Div Geriatr, Dept ofMedicine, San Francisco, CA 94121 USA. [Byers, Amy L.; Hoang, Tina; Covinsky, Kenneth E.; Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. [Lui, Li-Yung] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Blazer, Dan G.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. [Ensrud, Kristine E.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Ensrud, Kristine E.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Ensrud, Kristine E.] Minneapolis Vet Affairs Med Ctr, Minneapolis, MN USA. [Cauley, Jane A.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Hillier, Teresa A.] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. [Fredman, Lisa] Boston Univ, Dept Epidemiol, Boston, MA 02215 USA. RP Byers, AL (reprint author), Univ Calif San Francisco, Dept Psychiat, 4150 Clement St,Mail Code 116H, San Francisco, CA 94121 USA. EM Amy.Byers@ucsf.edu OI Cauley, Jane A/0000-0003-0752-4408 FU National Institute of Mental Health [R01 MH086498, MH079093]; National Institute on Aging [AG031155]; Public Health Service from the National Institute of Arthritis and Musculoskeletal and Skin Diseases [2 R01 AG027574-22A1, R01 AG005407, R01 AG027576-22, 2 R01 AG005394-22A1, AG05407, AG05394, AR35582, AR35583, AR35584, AG026720, R01 AG18037, R01 AG028144-01A1]; National Institute on Aging FX This work was supported by grants R01 MH086498 from the National Institute of Mental Health (Dr Yaffe), which was administered by the Northern California Institute for Research and Education and with resources of the San Francisco Veterans Affairs Medical Center, K01 Career Development Award MH079093 from the National Institute of Mental Health (Dr Byers), and K24 Midcareer Investigator Award AG031155 from the National Institute on Aging (Dr Yaffe). The Study of Osteoporotic Fractures was supported by Public Health Service grants 2 R01 AG027574-22A1, R01 AG005407, R01 AG027576-22, 2 R01 AG005394-22A1, AG05407, AG05394, AR35582, AR35583, AR35584, AG026720, R01 AG18037, and R01 AG028144-01A1 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute on Aging. NR 48 TC 40 Z9 42 U1 4 U2 17 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD OCT PY 2012 VL 69 IS 10 BP 1073 EP 1079 PG 7 WC Psychiatry SC Psychiatry GA 014YV UT WOS:000309412800010 PM 23026957 ER PT J AU Schumacher, HR Evans, RR Saag, KG Clower, J Jennings, W Weinstein, SP Yancopoulos, GD Wang, J Terkeltaub, R AF Schumacher, H. Ralph, Jr. Evans, Robert R. Saag, Kenneth G. Clower, James Jennings, William Weinstein, Steven P. Yancopoulos, George D. Wang, Jian Terkeltaub, Robert TI Rilonacept (interleukin-1 trap) for prevention of gout flares during initiation of uric acid-lowering therapy: Results from a phase III randomized, double-blind, placebo-controlled, confirmatory efficacy study SO ARTHRITIS CARE & RESEARCH LA English DT Article ID HEALTH-CARE UTILIZATION; IL-1 INHIBITION; RENAL-DISEASE; ARTHRITIS; MANAGEMENT; ANAKINRA; INFLAMMATION; ALLOPURINOL; PREVALENCE; ADHERENCE AB Objective To evaluate the efficacy and safety of the interleukin-1 inhibitor rilonacept (interleukin-1 Trap) for gout flare prevention during initiation of uric acidlowering therapy (ULT). Methods In total, 241 adult patients with gout, =2 gout flares within the past year, and a serum urate level =7.5 mg/dl were initiated on allopurinol 300 mg daily and randomly allocated in a 1:1:1 ratio to receive 16 once-weekly subcutaneous injections of placebo, rilonacept 80 mg, or rilonacept 160 mg, with a double (loading) dose on day 1. Allopurinol was titrated to achieve a serum urate level of <6.0 mg/dl. The study was powered for the primary efficacy end point, the number of gout flares per patient through week 16. Results More patients in the rilonacept groups (80.0% in the rilonacept 80 mg group, 86.4% in the rilonacept 160 mg group) completed the study than in the placebo group (72.5%; P < 0.05 for the rilonacept 160 mg group versus the placebo group). Over 16 weeks, the mean number of gout flares per patient was significantly reduced by rilonacept treatment (placebo: 1.06, rilonacept 80 mg: 0.29 [P < 0.001], rilonacept 160 mg: 0.21 [P < 0.001]). Significantly lower proportions of patients reported =1 gout flares with rilonacept 80 mg (18.8%) and rilonacept 160 mg (16.3%) relative to placebo (46.8%; P < 0.001 for both). Except for injection site reactions (1.3% in the placebo group versus 8.8% in the rilonacept 80 mg group [P = 0.0635, post hoc analysis] and 19.8% in the rilonacept 160 mg group [P = 0.0001, post hoc analysis]), the incidence of adverse events was generally balanced among the treatment groups. Conclusion Rilonacept markedly reduced the occurrence of gout flares associated with the initiation of ULT. The efficacy and safety profile suggests that rilonacept may have the potential to improve long-term disease control for some patients by improving adherence to ULT by reducing flares during the first months after ULT initiation. C1 [Schumacher, H. Ralph, Jr.] Univ Penn, Philadelphia, PA 19104 USA. [Schumacher, H. Ralph, Jr.] VA Med Ctr, Philadelphia, PA USA. [Evans, Robert R.; Weinstein, Steven P.; Yancopoulos, George D.; Wang, Jian] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. [Clower, James] Westside Ctr Clin Res & Baptist Primary Care, Jacksonville, FL USA. [Jennings, William] Radiant Res, San Antonio, TX USA. [Terkeltaub, Robert] Univ Calif San Diego, San Diego, CA 92103 USA. [Terkeltaub, Robert] VA Healthcare Syst San Diego, San Diego, CA USA. [Saag, Kenneth G.] Univ Alabama Birmingham, Birmingham, AL USA. RP Schumacher, HR (reprint author), Philadelphia VA Med Ctr, 151K,Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM schumacr@mail.med.upenn.edu FU Regeneron Pharmaceuticals; Regeneron; Takeda; Novartis; Ardea; Pfizer; Savient; URL FX Supported by Regeneron Pharmaceuticals.; Dr. Schumacher has received consultancy fees, speaking fees, and/or honoraria (less than $10,000 each) from Regeneron, Takeda, Novartis, Ardea, and Pfizer. Dr. Evans owns stock or stock options in Regeneron. Dr. Saag has received consultancy fees, speaking fees, and/or honoraria (less than $10,000 each) from Takeda, Novartis, Ardea, and Savient. Dr. Weinstein owns stock or stock options in Regeneron and holds a patent licensed to Regeneron for Arcalyst (rilonacept). Dr. Yancopoulos owns stock or stock options in Regeneron and holds a patent licensed to Regeneron for Arcalyst (rilonacept). Dr. Wang owns stock or stock options in Regeneron. Dr. Terkeltaub has received consultancy fees, speaking fees, and/or honoraria (less than $10,000 each) from Regeneron, Novartis, URL, Takeda, Ardea, and Pfizer, and has served as a paid consultant to Leerink Swann Investment Banking Group. NR 48 TC 43 Z9 44 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD OCT PY 2012 VL 64 IS 10 BP 1462 EP 1470 DI 10.1002/acr.21690 PG 9 WC Rheumatology SC Rheumatology GA 014QV UT WOS:000309391700003 PM 22549879 ER PT J AU Carroll, L Perumal, M Vasdev, N Robins, E Aboagye, EO AF Carroll, Laurence Perumal, Meg Vasdev, Neil Robins, Edward Aboagye, Eric O. TI Radiosynthesis and in vivo tumor uptake of 2-deoxy-2-[F-18]fluoro-myo-inositol SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Fluorine-18; Inositol; Cancer; PET Imaging ID PET; FLUORINATION; CELLS AB Inositols play an important role in membrane lipid metabolism and mitogenic signaling of most cancer cells. There is paucity of data on the distribution of radiolabelled inositols. Based on work previously carried out on 1-deoxy-1-[F-18]fluoro-scyllo-inositol ([F-18]2), we began a program of work to label myo-inositol (2-deoxy-2-[F-18]fluoro-myo-inositol, [F-18]1), the most abundant inositol in cells. Fluorination of a triflate precursor 4 afforded the desired [F-18]1 following deprotection with a radiochemical yield of 8% n.d.c. [F-18]1 showed higher uptake in vivo in a human breast cancer xenograft model, MDA-MB-231, compared to [F-18]2. Thus, we have developed a new inositol radiotracer that could have utility for studying inositol uptake in tumors. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Carroll, Laurence; Perumal, Meg; Aboagye, Eric O.] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, Comprehens Canc Imaging Ctr, London W12 0NN, England. [Vasdev, Neil] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Vasdev, Neil] Massachusetts Gen Hosp, Dept Nucl Med & Mol Imaging, Boston, MA 02114 USA. [Robins, Edward] GE Healthcare Immanet, London W12 0NN, England. RP Aboagye, EO (reprint author), Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, Comprehens Canc Imaging Ctr, Hammersmith Campus, London W12 0NN, England. EM eric.aboagye@imperial.ac.uk FU CR-UK&EPSRC Cancer Imaging Centre at Imperial College London; MRC; Department of Health (England) [C2536/A10337]; UK Medical Research Council [U.1200.02.005.00001.01] FX Funding provided by CR-UK&EPSRC Cancer Imaging Centre at Imperial College London, in association with the MRC and Department of Health (England) Grant C2536/A10337 and UK Medical Research Council core funding grant U.1200.02.005.00001.01. We would also like to thank Dr. Mark Nitz for providing a sample of compound 3. NR 13 TC 4 Z9 4 U1 0 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD OCT 1 PY 2012 VL 22 IS 19 BP 6148 EP 6150 DI 10.1016/j.bmcl.2012.08.022 PG 3 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 010OZ UT WOS:000309105200022 PM 22944120 ER PT J AU Miller, CL Specht, MC Skolny, MN Jammallo, LS Horick, N O'Toole, J Coopey, SB Hughes, K Gadd, M Smith, BL Taghian, AG AF Miller, Cynthia L. Specht, Michelle C. Skolny, Melissa N. Jammallo, Lauren S. Horick, Nora O'Toole, Jean Coopey, Suzanne B. Hughes, Kevin Gadd, Michele Smith, Barbara L. Taghian, Alphonse G. TI Sentinel lymph node biopsy at the time of mastectomy does not increase the risk of lymphedema: implications for prophylactic surgery SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Prophylactic mastectomy; Breast cancer-related lymphedema; Sentinel lymph node biopsy; Bilateral mastectomy; Arm swelling ID QUALITY-OF-LIFE; BREAST-CANCER PATIENTS; STANDARD AXILLARY TREATMENT; ARM MORBIDITY; GROUP TRIAL; DISSECTION; WOMEN; COMPLICATIONS; CARCINOMA; EFFICACY AB Women diagnosed with or at high risk for breast cancer increasingly choose prophylactic mastectomy. It is unknown if adding sentinel lymph node biopsy (SLNB) to prophylactic mastectomy increases the risk of lymphedema. We sought to determine the risk of lymphedema after mastectomy with and without nodal evaluation. 117 patients who underwent bilateral mastectomy were prospectively screened for lymphedema. Perometer arm measurements were used to calculate weight-adjusted arm volume change at each follow-up. Of 234 mastectomies performed, 15.8 % (37/234) had no axillary surgery, 63.7 % (149/234) had SLNB, and 20.5 % (48/234) had axillary lymph node dissection (ALND). 88.0 % (103/117) of patients completed the LEFT-BC questionnaire evaluating symptoms associated with lymphedema. Multivariate analysis was used to assess clinical characteristics associated with increased weight-adjusted arm volume and patient-reported lymphedema symptoms. SLNB at the time of mastectomy did not result in an increased mean weight-adjusted arm volume compared to mastectomy without axillary surgery (p = 0.76). Mastectomy with ALND was associated with a significantly greater mean weight-adjusted arm volume change compared to mastectomy with SLNB (p < 0.0001) and without axillary surgery (p = 0.0028). Patients who underwent mastectomy with ALND more commonly reported symptoms associated with lymphedema compared to those with SLNB or no axillary surgery (p < 0.0001). Patients who underwent mastectomy with SLNB or no axillary surgery reported similar lymphedema symptoms. Addition of SLNB to mastectomy is not associated with a significant increase in measured or self-reported lymphedema rates. Therefore, SLNB may be performed at the time of prophylactic mastectomy without an increased risk of lymphedema. C1 [Specht, Michelle C.; Coopey, Suzanne B.; Hughes, Kevin; Gadd, Michele; Smith, Barbara L.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Miller, Cynthia L.; Skolny, Melissa N.; Jammallo, Lauren S.; Taghian, Alphonse G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Horick, Nora] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [O'Toole, Jean] Massachusetts Gen Hosp, Dept Phys & Occupat Therapy, Boston, MA 02114 USA. RP Specht, MC (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, 55 Fruit St, Boston, MA 02114 USA. EM mspecht@partners.org OI Hughes, Kevin/0000-0003-4084-6484 FU National Cancer Institute [R01CA139118, P50CA089393] FX The project described was supported by Award Number R01CA139118 (AGT), Award Number P50CA089393 (AGT) from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 49 TC 6 Z9 6 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD OCT PY 2012 VL 135 IS 3 BP 781 EP 789 DI 10.1007/s10549-012-2231-1 PG 9 WC Oncology SC Oncology GA 003ZB UT WOS:000308648800015 PM 22941538 ER PT J AU Freedman, RA Virgo, KS Labadie, J He, YL Partridge, AH Keating, NL AF Freedman, Rachel A. Virgo, Katherine S. Labadie, Julia He, Yulei Partridge, Ann H. Keating, Nancy L. TI Receipt of locoregional therapy among young women with breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Young women; Locoregional therapy; Radiation ID ADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIAL; OLDER WOMEN; POSTMASTECTOMY RADIOTHERAPY; POSTOPERATIVE RADIOTHERAPY; CONSERVATIVE SURGERY; RADIATION-THERAPY; PROGNOSTIC-FACTOR; INSURANCE STATUS; UNITED-STATES AB Although younger women with breast cancer have the most to gain from receipt of optimal care, few data are available regarding their receipt of locoregional breast cancer treatments. We identified 317,596 women aged 18-64 who were diagnosed with invasive breast cancer at hospitals reporting to the National Cancer Database, a large national cancer registry, during 2004-2008. We used multivariable logistic regression to assess the association of patient age with mastectomy versus breast-conserving surgery (BCS), radiation with BCS, and postmastectomy radiation therapy (PMRT) with varying indications, adjusting for patient, clinical, and facility characteristics. Overall, 4 % of women were 35 years old or younger and 7 % were 36-40 years old. Women a parts per thousand currency signage 40 were significantly more likely to have mastectomy than BCS compared with older women (57 % for age a parts per thousand currency sign35 and 52 % for ages 36-40 vs. 35 % for ages 61-64, adjusted odds ratio [OR] for age a parts per thousand currency sign35 = 2.03; 95 % confidence interval (CI) 1.93-2.14 and OR for ages 36-40 = 1.76; 95 % CI 1.69-1.84). Younger women were less likely to receive radiation if BCS was performed (69 and 73 vs. 80 %, OR for age a parts per thousand currency sign35 = 0.69; 95 % CI 0.65-0.74 and OR for ages 36-40 = 0.74; 95 % CI 0.70-0.78). For those who underwent mastectomy, overall rates of PMRT were low, although women a parts per thousand currency signage 35 and ages 36-40 (vs. ages 61-64) were more likely to receive PMRT regardless of clinical indications. Our study suggests that young women with breast cancer may not be receiving optimal locoregional therapy. Efforts are needed to confirm these findings, further understand barriers to care, and increase the receipt of appropriate adjuvant radiation therapy among young women to improve their disease-free and overall survival. C1 [Freedman, Rachel A.; Partridge, Ann H.] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. [Virgo, Katherine S.; Labadie, Julia] Amer Canc Soc, Hlth Serv Res Program, Intramural Res Dept, Natl Home Off, Atlanta, GA 30329 USA. [He, Yulei; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02215 USA. [Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. RP Freedman, RA (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM rafreedman@partners.org FU Susan G. Komen for the Cure Foundation; American Cancer Society FX We thank the National Cancer Data Base staff and American Cancer Society for their collaboration on this study and for their ongoing development, maintenance, and improvement of this registry. This study was funded by the Susan G. Komen for the Cure Foundation and American Cancer Society Intramural Research Funding. NR 57 TC 12 Z9 12 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD OCT PY 2012 VL 135 IS 3 BP 893 EP 906 DI 10.1007/s10549-012-2156-8 PG 14 WC Oncology SC Oncology GA 003ZB UT WOS:000308648800027 PM 22949130 ER PT J AU Young, P Kim, B Malin, JL AF Young, Patricia Kim, Benjamin Malin, Jennifer L. TI Preoperative breast MRI in early-stage breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Magnetic resonance imaging, Functional; Decision analysis; Technology; Assessment ID RANDOMIZED CONTROLLED-TRIAL; 20-YEAR FOLLOW-UP; COST-EFFECTIVENESS; RADIATION-THERAPY; CONSERVATIVE SURGERY; SURGICAL-MANAGEMENT; CONSERVING SURGERY; MASTECTOMY; IMPACT; CARCINOMA AB Rapid uptake of new imaging technology is a major contributor to rising healthcare costs. Preoperative breast magnetic resonance imaging (MRI) for patients with early-stage breast cancer has dramatically increased in use without the evidence of improved outcomes compared to standard assessment and is associated with higher rates of mastectomy. A decision analytic model was developed to evaluate the impact of adding breast MRI to the preoperative evaluation of women with early-stage breast cancer who were candidates for breast-conserving therapy on patient outcomes measured in quality-adjusted life years (QALYs). Model inputs, including survival, recurrence rates, and health utilities, were obtained from a comprehensive literature review. One-way sensitivity analyses were performed to estimate threshold values for key parameters at which adding MRI would become the optimal imaging strategy over standard assessment. Preoperative MRI resulted in 17.77 QALYs compared to 17.86 QALYs with standard assessment, a decrease of 0.09 QALYs or 34 days. In sensitivity analyses, standard assessment was associated with better patient outcomes than preoperative breast MRI across all plausible probabilities for mastectomy, local recurrence, and health utilities. For routine preoperative breast MRI to become the optimal strategy, the conversion rate to mastectomy after preoperative MRI would need to be < 1 % (versus the range of 3.6-33 % reported in the literature). Routine preoperative breast MRI appears to confer no advantage over the standard diagnostic evaluations for early-stage breast cancer and may lead to worse patient outcomes. C1 [Young, Patricia] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Young, Patricia; Malin, Jennifer L.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Kim, Benjamin] UCSF Sch Med, Div Hematol Oncol, Dept Med, San Francisco, CA USA. [Kim, Benjamin; Malin, Jennifer L.] RAND Corp, Santa Monica, CA USA. [Malin, Jennifer L.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. [Malin, Jennifer L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Young, P (reprint author), Cedars Sinai Med Ctr, 8700 Beverly Blvd,Suite 5512, Los Angeles, CA 90048 USA. EM pyoung@mednet.ucla.edu NR 42 TC 7 Z9 8 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD OCT PY 2012 VL 135 IS 3 BP 907 EP 912 DI 10.1007/s10549-012-2207-1 PG 6 WC Oncology SC Oncology GA 003ZB UT WOS:000308648800028 PM 22923237 ER PT J AU Cserti-Gazdewich, CM Dhabangi, A Musoke, C Ssewanyana, I Ddungu, H Nakiboneka-Ssenabulya, D Nabukeera-Barungi, N Mpimbaza, A Dzik, WH AF Cserti-Gazdewich, Christine M. Dhabangi, Aggrey Musoke, Charles Ssewanyana, Isaac Ddungu, Henry Nakiboneka-Ssenabulya, Deborah Nabukeera-Barungi, Nicolette Mpimbaza, Arthur Dzik, Walter H. TI Cytoadherence in paediatric malaria: ABO blood group, CD36, and ICAM1 expression and severe Plasmodium falciparum infection SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE Malaria; ABO; Anaemia; Platelet; CD36; ICAM1 ID SICKLE-CELL TRAIT; PLATELET GLYCOPROTEIN IV; GROUP-A ANTIGEN; CEREBRAL MALARIA; ENDOTHELIAL-CELLS; MICROVASCULAR SEQUESTRATION; PARASITIZED ERYTHROCYTES; TRANSMISSION AREA; AFRICAN CHILDREN; INNATE IMMUNITY AB As a leading cause of childhood mortality worldwide, selection pressure by Plasmodium falciparum continues to shape the human genome. Severe disturbances within the microcirculation result from the adhesion of infected erythrocytes to host receptors on monocytes, platelets, and endothelium. In this prospective study, we compared expression of all major host cytoadhesion receptors among Ugandan children presenting with uncomplicated malaria (n = 1078) versus children with severe malaria (n = 855), including cerebral malaria (n = 174), severe anaemia (n = 522), and lactic acidosis (n = 154). We report a significant survival advantage attributed to blood group O and increased monocyte expression of CD36 and ICAM1 (CD54). The high case fatality rate syndromes of cerebral malaria and lactic acidosis were associated with high platelet CD36 expression and thrombocytopenia, and severe malaria anaemia was characterized by low ICAM1 expression. In a logistic regression model of disease severity, odds ratios for the mitigating effects of blood group O, CD36, and ICAM1 phenotypes were greater than that of sickle haemoglobin. Host genetic adaptations to Plasmodium falciparum suggest new potential malaria treatment strategies. C1 [Cserti-Gazdewich, Christine M.] Univ Toronto, Univ Hlth Network, Toronto, ON, Canada. [Dhabangi, Aggrey; Musoke, Charles; Ddungu, Henry; Nakiboneka-Ssenabulya, Deborah; Nabukeera-Barungi, Nicolette; Mpimbaza, Arthur] Makerere Univ, Coll Hlth Sci, Mulago Hosp, Kampala, Uganda. [Ssewanyana, Isaac] CPHL, Kampala, Uganda. [Ddungu, Henry] APCA, Kampala, Uganda. [Ddungu, Henry] Uganda Canc Inst, Kampala, Uganda. [Nakiboneka-Ssenabulya, Deborah] London Sch Hyg & Trop Med, London WC1, England. [Dzik, Walter H.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA USA. RP Cserti-Gazdewich, CM (reprint author), Toronto Gen Hosp, Dept Med, Dept Lab Hematol, Blood Transfus Med Lab, 3EC-306,200 Elizabeth St, Toronto, ON M5G 2C4, Canada. EM christine.cserti@uhn.ca FU International Society of Blood Transfusion Foundation (ISBT); National Blood Foundation (NBF); University of Toronto; Robert and Evelyn Luick Fund FX Grant support was provided by the International Society of Blood Transfusion Foundation (ISBT), the National Blood Foundation (NBF), the University of Toronto Dean's Fund for New Faculty, and the Robert and Evelyn Luick Fund. We are grateful to all the paediatric patients and their families who agreed to participate in this study, the staff of the MU-UCSF MoLab, the staff of the JCRC Flow Cytometry Lab, the director of the Uganda National Blood Transfusion Service (Dr Dorothy Kyeyune), biostatistical support (Dr Brian Healy, Massachusetts General Hospital), and our web design and database support (Eileen Selogie). Support for reagents and equipment was provided by Beckman Coulter Corporation, Becton Dickinson [BD Biosciences], Masimo Corporation, Whatman Corporation, Bayer, Nonin Medical, and Heart to Heart International. NR 57 TC 10 Z9 10 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2012 VL 159 IS 2 BP 223 EP 236 DI 10.1111/bjh.12014 PG 14 WC Hematology SC Hematology GA 012NC UT WOS:000309242000014 PM 22909232 ER PT J AU Holmgren, SC Goren, EM Wood, BL Becker, PS Taylor, JA AF Holmgren, Sigrid C. Goren, Emily M. Wood, Brent L. Becker, Pamela S. Taylor, Jason A. TI Immune defects in a mouse model of Fanconi anaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter DE Fanconi anaemia; vaccination; immune defects; human papillomavirus ID HEAD C1 [Holmgren, Sigrid C.; Goren, Emily M.; Taylor, Jason A.] Portland VA Med Ctr, Portland, OR USA. [Wood, Brent L.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Wood, Brent L.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Becker, Pamela S.] Univ Washington, Div Hematol, Seattle, WA 98195 USA. [Taylor, Jason A.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Holmgren, SC (reprint author), Portland VA Med Ctr, Portland, OR USA. EM taylojas@ohsu.edu NR 9 TC 2 Z9 2 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2012 VL 159 IS 2 BP 246 EP 250 DI 10.1111/bjh.12012 PG 5 WC Hematology SC Hematology GA 012NC UT WOS:000309242000018 PM 22897682 ER PT J AU Smith, MA Schnellmann, RG AF Smith, Matthew A. Schnellmann, Rick G. TI Calpains, mitochondria, and apoptosis SO CARDIOVASCULAR RESEARCH LA English DT Review DE Calpains; Apoptosis; Mitochondria; Cardiovascular system ID RENAL-CELL DEATH; MYOFIBRILLAR PROTEIN TURNOVER; CALCIUM-DEPENDENT PROTEASE; REDUCES INFARCT SIZE; MU-CALPAIN; ENDOTHELIAL-CELLS; PERMEABILITY TRANSITION; SKELETAL-MUSCLE; CA-2&-ACTIVATED PROTEASE; SIGNALING PATHWAYS AB Mitochondrial activity is critical for efficient function of the cardiovascular system. In response to cardiovascular injury, mitochondrial dysfunction occurs and can lead to apoptosis and necrosis. Calpains are a 15-member family of Ca-2-activated cysteine proteases localized to the cytosol and mitochondria, and several have been shown to regulate apoptosis and necrosis. For example, in endothelial cells, Ca-2 overload causes mitochondrial calpain 1 cleavage of the Na/Ca-2 exchanger leading to mitochondrial Ca-2 accumulation. Also, activated calpain 1 cleaves Bid, inducing cytochrome c release and apoptosis. In renal cells, calpains 1 and 2 promote apoptosis and necrosis by cleaving cytoskeletal proteins, which increases plasma membrane permeability and cleavage of caspases. Calpain 10 cleaves electron transport chain proteins, causing decreased mitochondrial respiration and excessive activation, or inhibition of calpain 10 activity induces mitochondrial dysfunction and apoptosis. In cardiomyocytes, calpain 1 activates caspase 3 and poly-ADP ribose polymerase during tumour necrosis factor--induced apoptosis, and calpain 1 cleaves apoptosis-inducing factor after Ca-2 overload. Many of these observations have been elucidated with calpain inhibitors, but most calpain inhibitors are not specific for calpains or a specific calpain family member, creating more questions. The following review will discuss how calpains affect mitochondrial function and apoptosis within the cardiovascular system. C1 [Smith, Matthew A.; Schnellmann, Rick G.] Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Ctr Cell Death Injury & Regenerat, Charleston, SC 29425 USA. [Schnellmann, Rick G.] Ralph Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Schnellmann, RG (reprint author), Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Ctr Cell Death Injury & Regenerat, 280 Calhoun St,MSC140, Charleston, SC 29425 USA. EM schnell@musc.edu FU NIH [GM 084147, ES-012239, C06 RR-015455]; NIH/NIEHS Training Program in Environmental Stress Signaling [T32ES012878-05]; Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs FX This study was supported by NIH Grant (GM 084147), the NIH Grant (ES-012239), the NIH/NIEHS Training Program in Environmental Stress Signaling (T32ES012878-05), and by the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs. Animal facilities were funded by NIH grant (C06 RR-015455). NR 113 TC 74 Z9 81 U1 1 U2 68 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD OCT 1 PY 2012 VL 96 IS 1 BP 32 EP 37 DI 10.1093/cvr/cvs163 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 010CS UT WOS:000309072700007 PM 22581845 ER PT J AU Sauls, K de Vlaming, A Harris, BS Williams, K Wessels, A Levine, RA Slaugenhaupt, SA Goodwin, RL Pavone, LM Merot, J Schott, JJ Le Tourneau, T Dix, T Jesinkey, S Feng, YY Walsh, C Zhou, B Baldwin, S Markwald, RR Norris, RA AF Sauls, Kimberly de Vlaming, Annemarieke Harris, Brett S. Williams, Katherine Wessels, Andy Levine, Robert A. Slaugenhaupt, Susan A. Goodwin, Richard L. Pavone, Luigi Michele Merot, Jean Schott, Jean-Jacques Le Tourneau, Thierry Dix, Thomas Jesinkey, Sean Feng, Yuanyi Walsh, Christopher Zhou, Bin Baldwin, Scott Markwald, Roger R. Norris, Russell A. TI Developmental basis for filamin-A-associated myxomatous mitral valve disease SO CARDIOVASCULAR RESEARCH LA English DT Article DE Filamin-A; Serotonin; Myxomatous valve disease; Transglutaminase-2; Valve maturation ID CARDIAC VALVULAR DYSTROPHY; SIGNAL-TRANSDUCTION; HEART-DISEASE; SEROTONIN; GENE; 5-HYDROXYTRYPTAMINE; VALVULOPATHY; PROTEIN; MICE; SEROTONYLATION AB We hypothesized that the structure and function of the mature valves is largely dependent upon how these tissues are built during development, and defects in how the valves are built can lead to the pathological progression of a disease phenotype. Thus, we sought to uncover potential developmental origins and mechanistic underpinnings causal to myxomatous mitral valve disease. We focus on how filamin-A, a cytoskeletal binding protein with strong links to human myxomatous valve disease, can function as a regulatory interface to control proper mitral valve development. Filamin-A-deficient mice exhibit abnormally enlarged mitral valves during foetal life, which progresses to a myxomatous phenotype by 2 months of age. Through expression studies, in silico modelling, 3D morphometry, biochemical studies, and 3D matrix assays, we demonstrate that the inception of the valve disease occurs during foetal life and can be attributed, in part, to a deficiency of interstitial cells to efficiently organize the extracellular matrix (ECM). This ECM organization during foetal valve gestation is due, in part, to molecular interactions between filamin-A, serotonin, and the cross-linking enzyme, transglutaminase-2 (TG2). Pharmacological and genetic perturbations that inhibit serotonin-TG2-filamin-A interactions lead to impaired ECM remodelling and engender progression to a myxomatous valve phenotype. These findings illustrate a molecular mechanism by which valve interstitial cells, through a serotonin, TG, and filamin-A pathway, regulate matrix organization during foetal valve development. Additionally, these data indicate that disrupting key regulatory interactions during valve development can set the stage for the generation of postnatal myxomatous valve disease. C1 [Sauls, Kimberly; de Vlaming, Annemarieke; Harris, Brett S.; Williams, Katherine; Wessels, Andy; Markwald, Roger R.; Norris, Russell A.] Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Sch Med, Cardiovasc Dev Biol Ctr,Childrens Res Inst, Charleston, SC 29425 USA. [Levine, Robert A.] Massachusetts Gen Hosp, Dept Med, Noninvas Cardiac Lab, Boston, MA 02114 USA. [Slaugenhaupt, Susan A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Goodwin, Richard L.] Univ S Carolina, Sch Med, Dept Cell Biol & Anat, Columbia, SC 29209 USA. [Pavone, Luigi Michele] Univ Naples Federico II, Dept Biochem & Med Biotechnol, I-80131 Naples, Italy. [Merot, Jean; Schott, Jean-Jacques; Le Tourneau, Thierry] Inst Thorax, INSERM, UMR915, F-44007 Nantes, France. [Dix, Thomas; Jesinkey, Sean] S Carolina Coll Pharm, Dept Pharmaceut & Biomed Sci, Charleston, SC 29425 USA. [Feng, Yuanyi] Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA. [Walsh, Christopher] Harvard Univ, Sch Med, Dept Pediat & Neurol, Howard Hughes Med Inst,Div Genet,Childrens Hosp, Boston, MA 02115 USA. [Zhou, Bin] Yeshiva Univ Albert Einstein Coll Med, Dept Genet, Bronx, NY 10461 USA. [Baldwin, Scott] Vanderbilt Univ, Dept Pediat, Nashville, TN 37232 USA. RP Norris, RA (reprint author), Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Sch Med, Cardiovasc Dev Biol Ctr,Childrens Res Inst, 171 Ashley Ave, Charleston, SC 29425 USA. EM norrisra@musc.edu RI Schott, jean-Jacques/F-8842-2013; Pavone, Luigi Michele/H-3403-2012; Le Tourneau, Thierry/D-5428-2015; MEROT, Jean/D-5741-2015; OI Pavone, Luigi Michele/0000-0002-5145-7428 FU National Institutes of Health from the Extramural Research Facilities Program of the National Center for Research Resources [C06 RR018823]; National Heart Lung and Blood Institute [R01-HL078881, R01-HL07881S, R21-HL111770, R01HL084285, RO1-HL33756, R01HL086856]; NIH [C06 RR018823, C06 RR015455, COBRE P20RR016434-07, P20RR016434-09S1]; American Heart Association [09GRNT2060075, 11SDG5270006, SDG-0435128N]; National Science Foundation [EPS-0902795]; Foundation Leducq (Paris, France) Transatlantic Mitral Network of Excellence grant [07CVD04] FX This work was conducted in a facility constructed with support from the National Institutes of Health, Grant Number C06 RR018823 from the Extramural Research Facilities Program of the National Center for Research Resources. Other funding sources: National Heart Lung and Blood Institute: R01-HL078881 (B.Z.), R01-HL07881S (B.Z.), and R21-HL111770 (B.Z.), R01HL084285 (A.W.), RO1-HL33756 (R.R.M.), R01HL086856 (R.L.G.); NIH: C06 RR018823 (B.Z.), C06 RR015455 (B.Z.), COBRE P20RR016434-07 (R.R.M., A.W., R.A.N., B.S.H.), P20RR016434-09S1 (R.R.M. and R.A.N.); American Heart Association: 09GRNT2060075 (A.W.), 11SDG5270006 (R.A.N.), SDG-0435128N (B.Z.); National Science Foundation: EPS-0902795 (R.R.M. and R.A.N.); The Foundation Leducq (Paris, France) Transatlantic Mitral Network of Excellence grant 07CVD04 (R.A.N., R.R.M., R.A.L., S.A.S., J.M., J.J.S.). NR 42 TC 18 Z9 18 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD OCT 1 PY 2012 VL 96 IS 1 BP 109 EP 119 DI 10.1093/cvr/cvs238 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 010CS UT WOS:000309072700016 PM 22843703 ER PT J AU Nakai, H Kaku, K Takeuchi, M Otani, K Yoshitani, H Haruki, N Tamura, M Okazaki, M Abe, H Tsutsumi, A Levine, RA Otsuji, Y AF Nakai, Hiromi Kaku, Kyoko Takeuchi, Masaaki Otani, Kyoko Yoshitani, Hidetoshi Haruki, Nobuhiko Tamura, Masahito Okazaki, Masahiro Abe, Haruhiko Tsutsumi, Akizumi Levine, Robert A. Otsuji, Yutaka TI Different Influences of Left Ventricular Remodeling on Anterior and Posterior Mitral Leaflet Tethering-3-D Echocardiography Quantitative Analysis - SO CIRCULATION JOURNAL LA English DT Article DE Echocardiography; Heart failure; Mitral valve ID 3-DIMENSIONAL ECHOCARDIOGRAPHY; DILATED CARDIOMYOPATHY; PAPILLARY-MUSCLE; REGURGITATION; ANNULOPLASTY; INSIGHTS; REPAIR; DETERMINANTS; DYSFUNCTION; MECHANISM AB Background: Different influences of left ventricular (LV) remodeling on anterior and posterior mitral leaflet (AML and PML) tethering in ischemic mitre! regurgitation (MR) has not been fully investigated. We hypothesized that progressive outward displacement of papillary muscles, including posterior vector, may cause greater tethering to PML compared to AML. Methods and Results: In 79 patients with LV ejection fraction <50% and 20 controls, LV sphericity, AML and PML tethering angles, apical and posterior displacement of coaptation, mitral annular area, and severity of MR (vena contracta width) were measured using 3-D echocardiography. To examine different influences of LV remodeling on AML and PML tethering, interaction between AML/PML and LV sphericity was tested using multiple regression analysis. Both AML and PML tethering significantly increased with increased LV sphericity (r=0.59 and 0.65, P<0.001). Multiple regression yielded a significant interaction term between AML vs. LV sphericity and PML vs. LV sphericity (1=3.69, P<0.001), indicating greater influence from LV remodeling on PML compared to that for the AML. Multivariate analysis demonstrated independent contributions to MR severity from PML tethering primarily along with posterior and apical displacement of coaptation. Conclusions: LV remodeling augments tethering of both AML and PML, with greater influence on PML. (Circ J 2012; 76: 2481-2487) C1 [Otsuji, Yutaka] Univ Occupat & Environm Hlth, Sch Med, Dept Internal Med 2, Yahatanishi Ku, Kitakyushu, Fukuoka 8078555, Japan. [Tamura, Masahito] Univ Occupat & Environm Hlth, Sch Med, Kidney Ctr, Kitakyushu, Fukuoka 8078555, Japan. [Tsutsumi, Akizumi] Kitasato Univ, Sch Med, Dept Publ Hlth, Sagamihara, Kanagawa 228, Japan. [Levine, Robert A.] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Otsuji, Y (reprint author), Univ Occupat & Environm Hlth, Sch Med, Dept Internal Med 2, Yahatanishi Ku, Kitakyushu, Fukuoka 8078555, Japan. EM otsujiy@med.uoeh-u.ac.jp FU Japan Society for the Promoting of Science, Tokyo, Japan [21500458, 24500562, 19590972, 23500574, 23500632, 20590851] FX Y.O. was supported by Grant-in-Aids for Scientific Research 21500458 and 24500562, M. Tamura was supported by a Grant-in-Aid for Scientific Research 19590972, M. Takeuchi was supported by a Grant-in-Aid for Scientific Research 23500574, H.Y. was supported by a Grant-in-Aid for Scientific Research 23500632, and H.A. was supported by a Grant-in-Aid for Scientific Research 20590851 from Japan Society for the Promoting of Science, Tokyo, Japan. NR 29 TC 8 Z9 10 U1 0 U2 2 PU JAPANESE CIRCULATION SOC PI KYOTO PA KINKI INVENTION CENTER, 14 YOSHIDA KAWAHARACHO, SAKYO-KU, KYOTO, 606-8305, JAPAN SN 1346-9843 J9 CIRC J JI Circ. J. PD OCT PY 2012 VL 76 IS 10 BP 2481 EP 2487 DI 10.1253/circj.CJ-11-1527 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 013UM UT WOS:000309331400028 PM 22785152 ER PT J AU Yeung, AS Jing, YH Brenneman, SK Chang, TE Baer, L Hebden, T Kalsekar, I McQuade, RD Kurlander, J Siebenaler, J Fava, M AF Yeung, Albert S. Jing, Yonghua Brenneman, Susan K. Chang, Trina E. Baer, Lee Hebden, Tony Kalsekar, Iftekhar McQuade, Robert D. Kurlander, Jonathan Siebenaler, Jean Fava, Maurizio TI CLINICAL OUTCOMES IN MEASUREMENT-BASED TREATMENT (COMET): A TRIAL OF DEPRESSION MONITORING AND FEEDBACK TO PRIMARY CARE PHYSICIANS SO DEPRESSION AND ANXIETY LA English DT Article DE depressive disorder; primary health care; self report; questionnaires ID STAR-ASTERISK-D; TREATMENT-RESISTANT DEPRESSION; MENTAL-HEALTH-CARE; UNITED-STATES; COLLABORATIVE MANAGEMENT; ANTIDEPRESSANT TREATMENT; IMPROVE TREATMENT; RANDOMIZED-TRIAL; BLOOD-PRESSURE; SEVERITY AB Background Despite the availability of effective treatments for depression, many patients under the care of primary care physicians do not achieve remission. Clinical Outcomes in Measurement-based Treatment (COMET) was designed to assess whether communicating patient-reported depression symptom severity to primary care physicians affects patient outcomes at 6 months. Methods Nine hundred fifteen patients (intervention: n = 503; control: n = 412) diagnosed with major depressive disorder were enrolled in a prospective trial in which physician practice sites were assigned to either the intervention or control study arm. Only patients who were prescribed an antidepressant by their physician were eligible, but medication type was independent of the study protocol. Intervention-arm physicians received monthly updates on their patients depression severity, which was determined with the nine-item Patient Health Questionnaire (PHQ-9) administered during telephone interviews. Remission was defined as a PHQ-9 score <5 at 6 months; response was defined as a score reduction =50%. Results Among patients with baseline PHQ-9 score =5, 45.0% achieved remission (46.7% intervention versus 42.8% control) and 63.9% responded (67.0% intervention versus 59.7% control) at 6 months. After adjusting for baseline demographic and clinical variables, odds of remission (odds ratio [OR], 1.59 [95% CI, 1.072.37]) or response (OR, 2.02 [95% CI, 1.363.02]) were significantly greater for the intervention group than for control patients. Conclusions This study demonstrated that regular patient symptom monitoring with feedback to physicians improved outcomes of depression treatment in the primary care setting. Determining reasons for the high observed nonremission rates requires further investigation. C1 [Yeung, Albert S.; Chang, Trina E.; Baer, Lee; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Jing, Yonghua; Hebden, Tony; Kalsekar, Iftekhar] Bristol Myers Squibb Co, Plainsboro, NJ USA. [Brenneman, Susan K.; Kurlander, Jonathan] OptumInsight, Eden Prairie, MN USA. [Chang, Trina E.; Baer, Lee; Fava, Maurizio] Massachusetts Gen Hosp, Clin Trials Network & Inst, Boston, MA 02114 USA. [McQuade, Robert D.] Otsuka Pharmaceut Dev & Commercializat Inc, Princeton, NJ USA. [Siebenaler, Jean] OptumInsight, Cincinnati, OH USA. RP Yeung, AS (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 1 Bowdoin Sq,6th Fl, Boston, MA 02114 USA. EM ayeung@partners.org FU Alkermes; AstraZeneca; Euthymics; CeNeRx; Forest; GlaxoSmithKline; Johnson Johnson; Pfizer; Abbott Laboratories; Affectis Pharmaceuticals AG; Alkermes, Inc.; Amarin Pharma, Inc.; Aspect Medical Systems; Auspex Pharmaceuticals; Bayer AG; Best Practice Project Management, Inc.; BioMarin Pharmaceuticals, Inc.; Biovail Corporation; Bristol-Myers Squibb; Cephalon, Inc.; Clinical Trials Solutions; CNS Response, Inc.; Compellis Pharmaceuticals; Covance; Cypress Pharmaceutical, Inc.; DiagnoSearch Life Sciences (P) Ltd.; Dinippon Sumitomo Pharma Co., Inc.; Dov Pharmaceuticals, Inc.; Edgemont Pharmaceuticals, Inc.; Eisai, Inc.; Eli Lilly and Company; EnVivo; ePharmaSolutions; EPIX Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Fabre-Kramer Pharmaceuticals, Inc.; Forest Pharmaceuticals, Inc.; Ganeden; GenOmind, LLC; Grunenthal GmbH; i3 Innovus/Ingenix; Janssen Pharmaceutica; Jazz Pharmaceuticals, Inc.; Knoll Pharmaceuticals Corp.; Labopharm, Inc.; Lorex Pharmaceuticals; Lundbeck, Inc.; Lundbeck/Takeda; MedAvante, Inc.; Merck Co., Inc.; MSI Methylation Sciences, Inc.; Naurex, Inc.; NCCAM; Neuronetics, Inc.; NextWave Pharmaceuticals; NIDA; NIH; NIMH; Novartis; Nutrition 21; Orexigen Therapeutics, Inc.; Organon Pharmaceuticals; Otsuka Pharmaceuticals; PamLab, LLC; Pfizer, Inc.; PharmaStar; PsychoGenics; Psylin; Roche; Sanofi-Aventis; Scherring-Plough; Transcept; Otsuka Pharmaceutical Co., Ltd.; BrainCells, Inc.; Bristol-Myers Squibb (Princeton, NJ); Otsuka Pharmaceutical Co., Ltd. (Tokyo, Japan) FX Dr. Yeung and Dr. Baer have no financial relationships that pose a conflict of interest. Dr. Jing, Dr. Hebden, and Dr. Kalsekar are employees of Bristol-Myers Squibb and Dr. McQuade is an employee of Otsuka Pharmaceutical Co., Ltd. Dr. Brenneman, Dr. Siebenaler, and Mr. Kurlander are employees of OptumInsight (formerly Innovus), an independent research organization contracted by Bristol-Myers Squibb to conduct the study. Dr. Chang and Dr. Fava have relationships with companies with an interest in depression treatment, although no specific products are discussed in the manuscript. Dr. Chang has received lifetime research support from Alkermes, AstraZeneca, Euthymics, CeNeRx, Forest, GlaxoSmithKline, Johnson & Johnson, and Pfizer and has received travel reimbursement from Bristol-Myers Squibb. Dr. Fava has received research support from or served as a consultant to or on the board of numerous companies, including Abbott Laboratories; Affectis Pharmaceuticals AG; Alkermes, Inc.; Amarin Pharma, Inc.; Aspect Medical Systems; AstraZeneca; Auspex Pharmaceuticals; Bayer AG; Best Practice Project Management, Inc.; BioMarin Pharmaceuticals, Inc.; Biovail Corporation; BrainCells, Inc.; Bristol-Myers Squibb; CeneRx; Cephalon, Inc.; Clinical Trials Solutions; CNS Response, Inc.; Compellis Pharmaceuticals; Covance; Cypress Pharmaceutical, Inc.; DiagnoSearch Life Sciences (P) Ltd.; Dinippon Sumitomo Pharma Co., Inc.; Dov Pharmaceuticals, Inc.; Edgemont Pharmaceuticals, Inc.; Eisai, Inc.; Eli Lilly and Company; EnVivo; ePharmaSolutions; EPIX Pharmaceuticals, Inc.; Euthymics Bioscience, Inc.; Fabre-Kramer Pharmaceuticals, Inc.; Forest Pharmaceuticals, Inc.; Ganeden; GenOmind, LLC; GlaxoSmithKline; Grunenthal GmbH; i3 Innovus/Ingenix; Janssen Pharmaceutica; Jazz Pharmaceuticals, Inc.; Johnson & Johnson; Knoll Pharmaceuticals Corp.; Labopharm, Inc.; Lorex Pharmaceuticals; Lundbeck, Inc.; Lundbeck/Takeda; MedAvante, Inc.; Merck & Co., Inc.; MSI Methylation Sciences, Inc.; Naurex, Inc.; NCCAM; Neuronetics, Inc.; NextWave Pharmaceuticals; NIDA; NIH; NIMH; Novartis; Nutrition 21; Orexigen Therapeutics, Inc.; Organon Pharmaceuticals; Otsuka Pharmaceuticals; PamLab, LLC; Pfizer, Inc.; PharmaStar; PsychoGenics; Psylin; Roche; Sanofi-Aventis; Scherring-Plough; and Transcept.; Contract grant sponsor: Bristol-Myers Squibb; Contract grant sponsor: Otsuka Pharmaceutical Co., Ltd.; This study was funded by Bristol-Myers Squibb (Princeton, NJ) and Otsuka Pharmaceutical Co., Ltd. (Tokyo, Japan). The authors thank Angela K. Watkins, M. A. (OptumInsight), Elizabeth J. Davis, Ph.D. (medical writing, OptumInsight), Mia Eisenbart (OptumInsight Site Management Center), Ross Baker, Ph.D. (Otsuka Pharmaceutical), Edward Kim, M. D. (formerly of Bristol-Myers Squibb), Kurt Kroenke, MD (Regenstrief Institute, Inc.; Indiana University School of Medicine), and Michael Klinkman, M. S., M. D. (University of Michigan Department of Family Medicine). Findings were presented in part at NCDEU 2011, Boca Raton, June 13-16, 2011. NR 52 TC 16 Z9 16 U1 2 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD OCT PY 2012 VL 29 IS 10 BP 865 EP 873 DI 10.1002/da.21983 PG 9 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 014RY UT WOS:000309394600005 PM 22807244 ER PT J AU Mantovani, A Pavlicova, M Avery, D Nahas, Z McDonald, WM Wajdik, CD Holtzheimer, PE George, MS Sackeim, HA Lisanby, SH AF Mantovani, Antonio Pavlicova, Martina Avery, David Nahas, Ziad McDonald, William M. Wajdik, Chandra D. Holtzheimer, Paul E., III George, Mark S. Sackeim, Harold A. Lisanby, Sarah H. TI LONG-TERM EFFICACY OF REPEATED DAILY PREFRONTAL TRANSCRANIAL MAGNETIC STIMULATION (TMS) IN TREATMNT-RESISTANT DEPRESSION SO DEPRESSION AND ANXIETY LA English DT Article DE transcranial magnetic stimulation; efficacy; follow-up; treatment-resistant; depression ID MAJOR DEPRESSION; OPEN-LABEL; ELECTROCONVULSIVE-THERAPY; ANTIDEPRESSANT EFFICACY; RELAPSE; METAANALYSIS; MULTISITE; TRIAL; RTMS; PHARMACOTHERAPY AB Background A few studies have examined the durability of transcranial magnetic stimulation (TMS) antidepressant benefit once patients remitted. This study examined the long-term durability of clinical benefit from TMS using a protocol-specified TMS taper and either continuation pharmacotherapy or naturalistic follow-up. Methods Patients were remitters from an acute double-blind sham-controlled trial of TMS (n=18), or from an open-label extension in patients who did not respond to the acute trial (n=43). Long-term durability of TMS acute effect was examined in remitters over a 12-week follow-up. Relapse, defined as 24-item Hamilton Depression Rating Scale (HDRS-24) =20, was the primary outcome. Results Of 61 remitters in the acute trial, five entered naturalistic follow-up and 50 entered the TMS taper. Thirty-two patients completed TMS taper and 1-, 2-, and 3-month follow-up. At 3-month visit, 29 of 50 (58%) were classified as in remission (HDRS-24 =10), two of 50 (4%) as partial responders (30%= HDRS-24 reduction <50% from baseline), and one of 50 (2%) met criteria for relapse. During the entire 3-month follow-up, five of the 37 patients relapsed (relapse rate=13.5%), but four of them regained remission by the end of the study. The average time to relapse in these five patients was 7.2 +/- 3.3 weeks. Patients who relapsed had higher depression scores at 1 month. Conclusions While one third of the sample was lost to follow-up, our results demonstrate that most patients contributing to observations experienced persistence of benefit from TMS followed by pharmacotherapy or no medication. Longer follow-up and more rigorous studies are needed to explore the true long-term durability of remission produced by TMS. C1 [Mantovani, Antonio] Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Div Expt Therapeut, Dept Psychiat, New York, NY 10032 USA. [Mantovani, Antonio] Univ Siena, Div Psychiat, Dept Neurosci, I-53100 Siena, Italy. [Avery, David; Wajdik, Chandra D.] Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. [Nahas, Ziad] Amer Univ Beirut, Dept Psychiat, Beirut, Lebanon. [McDonald, William M.] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. [Holtzheimer, Paul E., III] Dartmouth Hitchcock Med Ctr, Dept Psychiat, Lebanon, NH 03766 USA. [George, Mark S.] Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. [George, Mark S.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Lisanby, Sarah H.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. RP Mantovani, A (reprint author), Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Div Expt Therapeut, Dept Psychiat, 1051 Riverside Dr,Unit 21, New York, NY 10032 USA. EM am2518@columbia.edu RI Holtzheimer, Paul/B-6212-2015 OI Holtzheimer, Paul/0000-0002-3552-3296 FU National Institute of Mental Health [5R01MH069929, 5R01MH069887, 5R01MH069896, 5R01MH069895, 5R01MH069886]; Eli Lilly and Company; Forest Pharmaceuticals; Northstar Neuroscience; Neuronetics Inc; Performance Plus; Takeda; Avanir Pharmaceutical; Aventis Pharmaceutical; Cyberonics Inc; Hope for Depression Research Foundation; Integra; Medtronic Inc; National Alliance of Research on Schizophrenia and Depression; National Institute of Mental Health; Neuropace; Neuronetics; St. Jude Medical Neuromodulation FX We thank the following, who were either compensated or uncompensated (u): Minnie Dobbins, MEd, MUSC (general administrative support), Judith E. Kiersky, Ph.D., Columbia University (external expert rater), and Elaine M. Dillingham, B. A., Columbia University (coordinated the expert rater tapes/ratings and the neuropsychological administration and scoring); Wenle Zhao, Ph.D. and Catherine Dillon from the MUSC Data Coordinating Center; data and safety monitoring board members: Scott L. Rauch, M. D., chairman, McLean Hospital, Belmont, Massachusetts; Eric Wassermann, M. D.(u), National Institute of Neurological Disorders and Stroke, Bethesda, Maryland; Cynthia Wainscott, Robert G. Robinson, M. D., The University of Iowa; and Hongbin Gu, Ph.D., University of North Carolina, Chapel Hill; MUSC site investigators, raters, and coordinators, including Xingbao Li, M. D., Samet Kose, M. D., Jeffrey J. Borckardt, Ph.D., Kevin Johnson, RN, Ph.D.; Columbia University site investigators, raters, and coordinators, including Linda Fitzsimons, M. S., R.N.C., Nancy Turret, L. C. S. W., Seth Disner, B. A., Austin Harrison, B. A., Matthew Truesdale, B. S., and Teresa Ngyuen, B. S.; Emory University site investigators, raters, and coordinators, including Sinead Quinn, Mustafa A. Mufti, M. D., Adriana P. Hermida, M. D., Boadie Dunlop, M. D., Charles M. Epstein, M. D., Ronald Chismar, R.N., Kimberly McWhorter, J. D., MPH, and Halima N. Garba; and University of Washington site investigators, raters, and coordinators, including Daniel Krashin, M. D., Tobias Dang, M. D., Chul Jin Shin, M. D., Rita Navarro, M. D., Wang-Ku Rho, M. D., Susan Bentley, M. D., David R. Haynor, M. D., Emily Rosenberger, B. A., Angela Ghesquiere, M. S. W., and Peter Roy-Byrne, M. D. This study was presented in abstract form at the American Psychiatric Association annual meeting, May 23, 2010; New Orleans, Louisiana. This study was supported by the National Institute of Mental Health funded Optimization of TMS for the Treatment of Depression Study (OPT-TMS) study involving grants 5R01MH069929 (Dr. Avery), 5R01MH069887 (Dr. George), 5R01MH069896 (Dr. George), 5R01MH069895 (Dr. Lisanby), and 5R01MH069886 (Dr. McDonald). Following a competitive bid and request involving all TMS manufacturers at the time of trial initiation, Neuronetics Inc. was selected and loaned the TMS devices, head holders, and coils for the trial and allowed use of the safety Investigational Device Exemption for their device.; Drs. Mantovani and Pavlikova have no financial interest to disclose. Dr. Avery reports research grants, speaking fees, or advisory board work with Eli Lilly and Company, Forest Pharmaceuticals, Northstar Neuroscience, Neuronetics Inc, Performance Plus, and Takeda. Dr. Nahas reports past and current research grants, speaking fees, or consulting work with Avanir Pharmaceutical, Aventis Pharmaceutical, Cyberonics Inc, Eli Lilly and Company, Hope for Depression Research Foundation, Integra, Medtronic Inc, National Alliance of Research on Schizophrenia and Depression, National Institute of Mental Health, Neuronetics Inc, and Neuropace (unpaid consultant). Dr. McDonald has received past research funding from Neuronetics. Dr. McDonald is also an unpaid consultant for NeuroStim. Dr. McDonald is on the faculty at Emory University which holds a patent on a TMS device. He receives no payment or royalties on this device. Chandra Wajdik has no financial interest to disclose. Dr. Holtzheimer has received consulting fees from St. Jude Medical Neuromodulation. Dr. George has been an unpaid advisor to Brainsonix, Brainsway, Neuronetics, Neostim and Neosync (as they make products related to TMS), and a paid advisor to Puretech ventures. The full amount of his advisory income has never been more than 10% of his university salary. MUSC has two patent applications in Dr. George's name on combining TMS with MRI imaging. He has no equity investment in any device or pharmaceutical company. Dr. Sackeim has served as a consultant to Cyberonics, Inc., Magstim Inc., MECTA Corp., and Neuronetics, Inc. Dr. Lisanby has served as PI on industry-sponsored research grants to Columbia/RFMH or Duke (Neuronetics (past), Brainsway, ANS/St. Jude, Cyberonics (past)); equipment loans to Columbia or Duke (Magstim, MagVenture); is co-inventor on a patent application for TMS technology not the topic of study here; and has no consultancies, speakers bureau memberships, board affiliations, or equity holdings in related industries. NR 29 TC 18 Z9 19 U1 3 U2 24 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD OCT PY 2012 VL 29 IS 10 BP 883 EP 890 DI 10.1002/da.21967 PG 8 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 014RY UT WOS:000309394600007 PM 22689290 ER PT J AU Steidtmann, D Manber, R Arnow, BA Klein, DN Markowitz, JC Rothbaum, BO Thase, ME Kocsis, JH AF Steidtmann, Dana Manber, Rachel Arnow, Bruce A. Klein, Daniel N. Markowitz, John C. Rothbaum, Barbara O. Thase, Michael E. Kocsis, James H. TI PATIENT TREATMENT PREFERENCE AS A PREDICTOR OF RESPONSE AND ATTRITION IN TREATMENT FOR CHRONIC DEPRESSION SO DEPRESSION AND ANXIETY LA English DT Article DE treatment outcome; treatment engagement ID BEHAVIORAL ANALYSIS SYSTEM; PRIMARY-CARE; MAJOR DEPRESSION; CHRONIC FORMS; PSYCHOTHERAPY; DISORDER; TRIAL; SYMPTOMATOLOGY AB Background Findings regarding the relationship between patient treatment preference and treatment outcome are mixed. This is a secondary data analysis investigating the relationship between treatment preference, and symptom outcome and attrition in a large two-phase depression treatment trial. Methods Patients met DSM-IV criteria for chronic forms of depression. Phase I was a 12-week, nonrandomized, open-label trial in which all participants (n = 785) received antidepressant medication(s) (ADM). Phase I nonremitters were randomized to Phase II, in which they received 12 weeks of either cognitive-behavioral system of psychotherapy (CBASP) + ADM (n = 193), brief supportive psychotherapy (BSP) + ADM (n = 187), or ADM only (n = 93). Participants indicated their treatment preference (medication only, combined treatment or no preference) at study entry. Symptoms were measured at 2-week intervals with the 24-item Hamilton Rating Scale for Depression (HAM-D). Results A large majority of patients reported a preference for combined treatment. Patients who preferred medication only were more likely to endorse a chemical imbalance explanation for depression, whereas those desiring combined treatment were more likely to attribute their depression to stressful experiences. In Phase I, patients who expressed no treatment preference showed greater rates of HAM-D symptom reduction than those with any preference, and patients with a preference for medication showed higher attrition than those preferring combined treatment. In Phase II, baseline treatment preference was not associated with symptom reduction or attrition. Conclusions Treatment preferences may moderate treatment response and attrition in unexpected ways. Research identifying factors associated with differing preferences may enable improved treatment retention and response. C1 [Steidtmann, Dana; Manber, Rachel; Arnow, Bruce A.] Stanford Univ, Dept Psychiat & Behav Sci, Sch Med, Stanford, CA 94305 USA. [Klein, Daniel N.] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. [Markowitz, John C.] Columbia Univ, New York State Psychiat Inst, New York, NY USA. [Rothbaum, Barbara O.] Emory Univ, Sch Med, Atlanta, GA USA. [Thase, Michael E.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Kocsis, James H.] Weill Cornell Med Coll, Dept Psychiat, New York, NY USA. RP Steidtmann, D (reprint author), Stanford Univ, Dept Psychiat & Behav Sci, Sch Med, 401 Quarry Rd, Stanford, CA 94305 USA. EM dsteidt@stanford.edu FU NIMH [UO1 MH62475, UO1 MH61587, UO1 MH62546, UO1 MH61562, UO1 MH63481, U01 MH62465, UO1 MH61590, UO1 MH61504, T32 MH019938, U01 MH62491, 5T32MH019938-18] FX Contract grant sponsor: NIMH; Contract grant numbers: UO1 MH62475 (James H. Kocsis), UO1 MH61587 (Michael E. Thase), UO1 MH62546 (Daniel N. Klein), UO1 MH61562 (Madhukar Trivedi), UO1 MH63481 (Philip Ninan and Barbara O. Rothbaum), U01 MH62465 (Alan J. Gelenberg), UO1 MH61590 (Martin B. Keller), UO1 MH61504 and T32 MH019938 (Alan F. Schatzberg), U01 MH62491 (James P. McCullough, Jr.); This work was supported by NIMH grants to Cornell University (UO1 MH62475; James H. Kocsis); University of Pittsburgh (UO1 MH61587; Michael E. Thase); Stony Brook University (UO1 MH62546; Daniel N. Klein); University of Texas Southwestern Medical Center (UO1 MH61562; Madhukar Trivedi); Emory University (UO1 MH63481; Philip Ninan and Barbara O. Rothbaum); University of Arizona (U01 MH62465; Alan J. Gelenberg); BrownUniversity (UO1 MH61590; Martin B. Keller); Stanford University (UO1 MH61504 and 5T32MH019938-18; Alan F. Schatzberg); and Virginia Commonwealth University (U01 MH62491; James P. McCullough, Jr.). All medications for this study were donated by Forest Laboratories, GlaxoSmithKline, Organon Pharmaceuticals Inc., Pfizer Inc., and Wyeth Pharmaceuticals. NR 32 TC 19 Z9 22 U1 1 U2 23 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1091-4269 J9 DEPRESS ANXIETY JI Depress. Anxiety PD OCT PY 2012 VL 29 IS 10 BP 896 EP 905 DI 10.1002/da.21977 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 014RY UT WOS:000309394600009 PM 22767424 ER PT J AU Hennings, JC Picard, N Huebner, AK Stauber, T Maier, H Brown, D Jentsch, TJ Vargas-Poussou, R Eladari, D Hubner, CA AF Hennings, J. Christopher Picard, Nicolas Huebner, Antje K. Stauber, Tobias Maier, Hannes Brown, Dennis Jentsch, Thomas J. Vargas-Poussou, Rosa Eladari, Dominique Huebner, Christian A. TI A mouse model for distal renal tubular acidosis reveals a previously unrecognized role of the V-ATPase a4 subunit in the proximal tubule SO EMBO MOLECULAR MEDICINE LA English DT Article DE deafness; distal renal tubular acidosis; H+-ATPase; kidney; proteinuria ID VACUOLAR H+-ATPASE; INTERCALATED CELLS; CL-/HCO3-EXCHANGER; PENDRED-SYNDROME; DENTS-DISEASE; MICE LACKING; B1 SUBUNIT; TARGETED DISRUPTION; METABOLIC-ACIDOSIS; PLASMA-MEMBRANE AB The V-ATPase is a multisubunit complex that transports protons across membranes. Mutations of its B1 or a4 subunit are associated with distal renal tubular acidosis and deafness. In the kidney, the a4 subunit is expressed in intercalated cells of the distal nephron, where the V-ATPase controls acid/base secretion, and in proximal tubule cells, where its role is less clear. Here, we report that a4 KO mice suffer not only from severe acidosis but also from proximal tubule dysfunction with defective endocytic trafficking, proteinuria, phosphaturia and accumulation of lysosomal material and we provide evidence that these findings may be also relevant in patients. In the inner ear, the a4 subunit co-localized with pendrin at the apical side of epithelial cells lining the endolymphatic sac. As a4 KO mice were profoundly deaf and displayed enlarged endolymphatic fluid compartments mirroring the alterations in pendrin KO mice, we propose that pendrin and the proton pump co-operate in endolymph homeostasis. Thus, our mouse model gives new insights into the divergent functions of the V-ATPase and the pathophysiology of a4-related symptoms. C1 [Hennings, J. Christopher; Huebner, Antje K.; Huebner, Christian A.] Univ Klinikum Jena, Inst Humangenet, Jena, Germany. [Picard, Nicolas; Eladari, Dominique] Univ Paris 05, Fac Med, Paris, France. [Picard, Nicolas; Eladari, Dominique] Ctr Rech Cordeliers, INSERM UMRS 872, Paris, France. [Stauber, Tobias; Jentsch, Thomas J.] Leibniz Inst Mol Pharmakol FMP, Berlin, Germany. [Stauber, Tobias; Jentsch, Thomas J.] Max Delbruck Ctr Mol Med MDC, Berlin, Germany. [Maier, Hannes] Hannover Med Sch, Klin Hals Nasen Ohrenheilkunde, Inst Audioneurotechnol, D-30623 Hannover, Germany. [Maier, Hannes] Hannover Med Sch, Klin Hals Nasen Ohrenheilkunde, Abt Expt Ohrenheilkunde, D-30623 Hannover, Germany. [Vargas-Poussou, Rosa] Harvard Univ, Massachusetts Gen Hosp, Simches Res Ctr, Sch Med,Ctr Syst Biol,Program Membrane Biol,Div N, Boston, MA USA. [Eladari, Dominique] Hop Europeen Georges Pompidou, AP HP, Serv Genet, Paris, France. RP Hubner, CA (reprint author), Univ Klinikum Jena, Inst Humangenet, Jena, Germany. EM dominique.eladari@crc.jussieu.fr; christian.huebner@mti.uni-jena.de RI Picard, Nicolas/B-6677-2012; Stauber, Tobias/E-4005-2010; Hannes, Maier/A-9457-2012; Hubner, Christian/A-2950-2017; OI Picard, Nicolas/0000-0002-1695-3389; Stauber, Tobias/0000-0003-0727-6109; Hannes, Maier/0000-0001-8457-5327; Hubner, Christian/0000-0002-1030-4943; Jentsch, Thomas/0000-0002-3509-2553 FU DFG [Hu 800/7-1]; INSERM; CNRS; l'Agence Nationale de la Recherche (ANR) [ANR BLANC 2010-R10164DD]; association pour l'information et la recherche sur les maladies renales genetiques (AIRG); l'ANR; La Societe Francaise d'Hypertension Arterielle (SFHTA); National Institutes of Health [DK42956]; Boston Area Diabetes and Endocrinology Research Center [NIH DK-57521]; Center for the Study of Inflammatory Bowel Disease [NIH DK-43351]; French Ministry of Health; European Community [201590]; French Tubulopathy Network FX We thank Katrin Schorr for excellent technical assistance and blastocyst injection, Peg McLaughlin for expert help with the immunogold EM and Robert Tyszkowski and Nicole Kronke for help with the immunofluorescence. This study was mainly funded by a grant of the DFG to CAH (Hu 800/7-1). Dominique Eladari is funded by INSERM, CNRS, by grant "HYPERCLO" ANR BLANC 2010-R10164DD from l'Agence Nationale de la Recherche (ANR) and by the grant 'subvention de recherche 2011' from the 'association pour l'information et la recherche sur les maladies renales genetiques (AIRG)'. Nicolas Picard is funded by a postdoctoral fellowship from l'ANR and by a grant 'subvention de Recherche 2011' from La Societe Francaise d'Hypertension Arterielle (SFHTA). This study was further supported by a grant from the National Institutes of Health to DB (DK42956). The Microscopy Core Facility of the Program in Membrane Biology receives additional support from the Boston Area Diabetes and Endocrinology Research Center (NIH DK-57521) and from the Center for the Study of Inflammatory Bowel Disease (NIH DK-43351). Rosa Vargas-Poussou was supported by funds from The French Ministry of Health (Plan Maladies Rares), and the European Community FP7 (EUNEFRON, 201590). We thank the French Tubulopathy Network for support and Carsten Wagner for providing antibodies. NR 65 TC 23 Z9 24 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1757-4676 J9 EMBO MOL MED JI EMBO Mol. Med. PD OCT PY 2012 VL 4 IS 10 BP 1057 EP 1071 DI 10.1002/emmm.201201527 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 015LA UT WOS:000309446200005 PM 22933323 ER PT J AU Kang, KJ Kim, KM Kim, JJ Rhee, PL Lee, JH Min, BH Rhee, JC Kushima, R Lauwers, GY AF Kang, K. J. Kim, K. -M. Kim, J. J. Rhee, P. -L. Lee, J. H. Min, B. -H. Rhee, J. C. Kushima, R. Lauwers, G. Y. TI Gastric extremely well-differentiated intestinal-type adenocarcinoma: a challenging lesion to achieve complete endoscopic resection SO ENDOSCOPY LA English DT Editorial Material ID CANCER AB Extremely well-differentiated tubular adenocarcinomas (EWDAs) of the stomach are characterized by surface maturation and their mimicking of intestinal metaplasia. Endoscopically, intramucosal EWDAs are frequently ill defined with indistinct borders due to the pallor of the neoplastic mucosa and the lack of contrast against the background atrophic and metaplastic mucosa. We evaluated the effectiveness of endoscopic resection for EWDAs after endoscopic submucosal dissection (ESD). Among 872 patients with early gastric cancer, 17 EWDAs were identified (1.9%). Endoscopically, the flat or depressed type was significantly more common among EWDAs (88.2%) than among early gastric cancers of other histologies (37.8%; P < 0.01). The discrepancy between endoscopically estimated tumor size and tumor size as confirmed in pathology reports was significantly greater among EWDAs (18.4 +/- 22.0 mm) than among others (5.8 +/- 7.5 mm). Involvement of the lateral resection margin was more common (29.4% vs. 2.5%; P < 0.05), and complete resection was achieved less often in EWDAs (47.1% vs. 80.4%; P = 0.01) compared to the others. EWDAs are associated with higher rates of incomplete resection after ESD, especially along the lateral margins. Pathologists should alert endoscopists when this diagnosis is made, with its associated risks; and endoscopists should pay particular attention to the extent of these tumors during resection. C1 [Kang, K. J.; Kim, J. J.; Rhee, P. -L.; Lee, J. H.; Min, B. -H.; Rhee, J. C.] Sungkyunkwan Univ, Dept Med, Samsung Med Ctr, Sch Med, Seoul 135710, South Korea. [Kim, K. -M.] Sungkyunkwan Univ, Dept Pathol, Samsung Med Ctr, Sch Med, Seoul 135710, South Korea. [Kushima, R.] Natl Canc Ctr, Clin Lab Div, Tokyo, Japan. [Lauwers, G. Y.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Kim, JJ (reprint author), Sungkyunkwan Univ, Dept Med, Samsung Med Ctr, Sch Med, 50 Irwon Dong, Seoul 135710, South Korea. EM jjkim@skku.edu; glauwers@partners.org NR 14 TC 5 Z9 5 U1 0 U2 2 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD OCT PY 2012 VL 44 IS 10 BP 949 EP 952 DI 10.1055/s-0032-1310161 PG 4 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 009XJ UT WOS:000309058400011 PM 22987215 ER PT J AU Albutt, K Bailen, L Fernandez-del Castillo, C AF Albutt, Katherine Bailen, Laurence Fernandez-del Castillo, Carlos TI A Patient With Recurrent Pancreatitis SO GASTROENTEROLOGY LA English DT Editorial Material C1 [Albutt, Katherine] Harvard Univ, Sch Med, William B Castle Soc, Boston, MA 02115 USA. [Bailen, Laurence] Newton Wellesley Hosp, Dept Gastroenterol, Newton, MA USA. [Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fernandez-del Castillo, Carlos] Pancreas & Biliary Surg Program, Boston, MA USA. RP Albutt, K (reprint author), Harvard Univ, Sch Med, William B Castle Soc, Boston, MA 02115 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2012 VL 143 IS 4 BP 896 EP + DI 10.1053/j.gastro.2012.04.019 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 014FY UT WOS:000309361800021 PM 22906398 ER PT J AU Falk, GW Buttar, NS Foster, NR Ziegler, KLA Demars, CJ Romero, Y Marcon, NE Schnell, T Corley, DA Sharma, P Cruz-Correa, MR Hur, C Fleischer, DE Chak, A Devault, KR Weinberg, DS Della'Zanna, G Richmond, E Smyrk, TC Mandrekar, SJ Limburg, PJ AF Falk, Gary W. Buttar, Navtej S. Foster, Nathan R. Ziegler, Katie L. Allen Demars, Catherine J. Romero, Yvonne Marcon, Norman E. Schnell, Thomas Corley, Douglas A. Sharma, Prateek Cruz-Correa, Marcia R. Hur, Chin Fleischer, David E. Chak, Amitabh Devault, Kenneth R. Weinberg, David S. Della'Zanna, Gary Richmond, Ellen Smyrk, Thomas C. Mandrekar, Sumithra J. Limburg, Paul J. CA Canc Prevention Network TI A Combination of Esomeprazole and Aspirin Reduces Tissue Concentrations of Prostaglandin E-2 in Patients With Barrett's Esophagus SO GASTROENTEROLOGY LA English DT Article DE Esophageal Cancer; NSAIDs; Inflammation; Esophagus ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RANDOMIZED-TRIAL; URSODEOXYCHOLIC ACID; CELL-PROLIFERATION; ADENOCARCINOMA; CYCLOOXYGENASE-2; PROGRESSION; CANCER; RISK; CHEMOPREVENTION AB BACKGROUND& AIMS: Proton pump inhibitors and nonsteroidal anti-inflammatory drugs might prevent esophageal adenocarcinoma in patients with Barrett's esophagus (BE), but there are limited data from clinical trials to support this concept. We conducted a randomized, double-blind, placebo-controlled, phase 2 trial to assess the effects of the combination of aspirin (3 different doses) and esomeprazole on tissue concentrations of prostaglandin (PG) E-2 in patients with BE with no dysplasia or low-grade dysplasia. METHODS: Participants were recruited through the multicenter Cancer Prevention Network and randomly assigned to groups that were given 40 mg esomeprazole twice daily in combination with an aspirin placebo once daily (arm A; n = 30), with 81 mg aspirin once daily (arm B; n = 47), or with 325 mg aspirin once daily (arm C; n = 45) for 28 days. We collected esophageal biopsy specimens before and after the intervention period to determine the absolute change in mean concentration of PGE(2) (the primary end point). RESULTS: Based on data from 114 patients, baseline characteristics were similar among groups. The absolute mean tissue concentration of PGE(2) was reduced by 67.6 +/- 229.68 pg/mL in arm A, 123.9 +/- 284.0 pg/mL in arm B (P = .10 vs arm A), and 174.9 +/- 263.62 pg/mL in arm C (P = .02 vs arm A). CONCLUSIONS: In combination with esomeprazole, short-term administration of higher doses of aspirin, but not lower doses or no aspirin, significantly reduced tissue concentrations of PGE(2) in patients with BE with either no dysplasia or low-grade dysplasia. These data support further evaluation of higher doses of aspirin and esomeprazole to prevent esophageal adenocarcinoma in these patients. Clinical trial registration number NCT00474903. C1 [Falk, Gary W.] Hosp Univ Penn, Div Gastroenterol, Philadelphia, PA 19104 USA. [Buttar, Navtej S.; Foster, Nathan R.; Ziegler, Katie L. Allen; Demars, Catherine J.; Romero, Yvonne; Smyrk, Thomas C.; Mandrekar, Sumithra J.; Limburg, Paul J.] Mayo Clin, Rochester, MN USA. [Marcon, Norman E.] St Michaels Hosp, Toronto, ON M5B 1W8, Canada. [Schnell, Thomas] Hines Vet Adm, Hines, IL USA. [Corley, Douglas A.] Kaiser Permanente Med Grp, San Francisco, CA USA. [Sharma, Prateek] Kansas City VA Med Ctr, Kansas City, MO USA. [Cruz-Correa, Marcia R.] Univ Puerto Rico, Ctr Canc, San Juan, PR 00936 USA. [Hur, Chin] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fleischer, David E.] Mayo Clin Arizona, Scottsdale, AZ USA. [Chak, Amitabh] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Devault, Kenneth R.] Mayo Clin Florida, Jacksonville, FL USA. [Weinberg, David S.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Della'Zanna, Gary; Richmond, Ellen] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. RP Falk, GW (reprint author), Hosp Univ Penn, Div Gastroenterol, Penn Tower,9th Floor,1 Convent Ave, Philadelphia, PA 19104 USA. EM gary.falk@uphs.upenn.edu OI Falk, Gary/0000-0002-7143-1436; Hur, Chin/0000-0002-2819-7576 FU National Cancer Institute [N01CN35000]; AstraZeneca; [M01-RR00585] FX The authors thank the staff of the Mayo Clinic Clinical Research Unit (supported by grant M01-RR00585); Drs Wilma Lingle, Schuyler Sanderson, Tsung-Teh Wu, and Kenneth Wang as well as Mary Fredericksen, Deb Geno, Colleen Garvey, Sharon Kaufman, and Maria Resner for their assistance with study design, administration, and manuscript preparation; and the dedicated study coordinators at the member organizations: Denise Buonocore-Sassano, Trish O'Brien, Sally Melloy, Jolanda DeBoer, April Higbee, Zehra Omer, Michael Lee, Barbara Berg, Maria Cirocco, Nancy Bassett, Beth Bednarchik, and Jessica Hernandez.; Supported by a contract from the National Cancer Institute (N01CN35000). Research support (equipment and drug supplies) was also provided by AstraZeneca, Bayer, and Boston Scientific.; The authors disclose the following: Dr Limburg served as a consultant for Genomic Health, Inc, from August 12, 2008, to April 19, 2010. Mayo Clinic has licensed Dr Limburg's intellectual property to Exact Sciences, and he and Mayo Clinic have contractual rights to receive royalties through this agreement. Dr Romero receives funding from AstraZeneca for Mayo Clinic Barrett's esophagus registry and tissue bank. The remaining authors disclose no conflicts. NR 42 TC 18 Z9 18 U1 0 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2012 VL 143 IS 4 BP 917 EP + DI 10.1053/j.gastro.2012.06.044 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 014FY UT WOS:000309361800023 PM 22796132 ER PT J AU Raina, A Papachristou, GI AF Raina, Amit Papachristou, Georgios I. TI A Rare Cause of Anemia SO GASTROENTEROLOGY LA English DT Editorial Material ID PANCREATITIS C1 [Raina, Amit] Univ Pittsburgh, Sch Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15260 USA. Vet Affairs Pittsburgh Hlth Syst, Pittsburgh, PA USA. RP Raina, A (reprint author), Univ Pittsburgh, Sch Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15260 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2012 VL 143 IS 4 BP E1 EP E2 DI 10.1053/j.gastro.2012.03.004 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 014FY UT WOS:000309361800001 PM 22921527 ER PT J AU Pinter, SF Sadreyev, RI Yildirim, E Jeon, Y Ohsumi, TK Borowsky, M Lee, JT AF Pinter, Stefan F. Sadreyev, Ruslan I. Yildirim, Eda Jeon, Yesu Ohsumi, Toshiro K. Borowsky, Mark Lee, Jeannie T. TI Spreading of X chromosome inactivation via a hierarchy of defined Polycomb stations SO GENOME RESEARCH LA English DT Article ID EMBRYONIC STEM-CELLS; XIST RNA; CHROMATIN-STRUCTURE; LINE-1 ELEMENTS; SAF-A; GENE; MOUSE; REPEAT; METHYLATION; EXPRESSION AB X chromosome inactivation (XCI) achieves dosage balance in mammals by repressing one of two X chromosomes in females. During XCI, the long noncoding Xist RNA and Polycomb proteins spread along the inactive X (Xi) to initiate chromosome-wide silencing. Although inactivation is known to commence at the X-inactivation center (Xic), how it propagates remains unknown. Here, we examine allele-specific binding of Polycomb repressive complex 2 (PRC2) and chromatin composition during XCI and generate a chromosome-wide profile of Xi and Xa (active X) at nucleosome-resolution. Initially, Polycomb proteins are localized to similar to 150 strong sites along the X and concentrated predominantly within bivalent domains coinciding with CpG islands ("canonical sites"). As XCI proceeds, similar to 4000 noncanonical sites are recruited, most of which are intergenic, nonbivalent, and lack CpG islands. Polycomb sites are depleted of LINE repeats but enriched for SINEs and simple repeats. Noncanonical sites cluster around the similar to 150 strong sites, and their H3K27me3 levels reflect a graded concentration originating from strong sites. This suggests that PRC2 and H3K27 methylation spread along a gradient unique to XCI. We propose that XCI is governed by a hierarchy of defined Polycomb stations that spread H3K27 methylation in cis. C1 [Pinter, Stefan F.; Sadreyev, Ruslan I.; Yildirim, Eda; Jeon, Yesu; Lee, Jeannie T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. [Pinter, Stefan F.; Sadreyev, Ruslan I.; Yildirim, Eda; Jeon, Yesu; Ohsumi, Toshiro K.; Borowsky, Mark; Lee, Jeannie T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. [Pinter, Stefan F.; Sadreyev, Ruslan I.; Yildirim, Eda; Jeon, Yesu; Ohsumi, Toshiro K.; Borowsky, Mark; Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Lee, JT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu OI Yildirim, Eda/0000-0002-4796-3854; Pinter, Stefan/0000-0003-4750-1403 FU German Research Foundation DFG; MGH ECOR Fund; Korean Research Foundation; NIH [RO1-GM090278] FX We thank members of our laboratory and the Bernstein laboratory for many valuable discussions. We also thank B.A. Chapman for bioinformatics suggestions. This work was supported by the German Research Foundation DFG (S.F.P.), the MGH ECOR Fund (E. V., Y.J.), a Korean Research Foundation grant (Y.J.), and the NIH (RO1-GM090278, J.T.L.). J.T.L. is an Investigator of the Howard Hughes Medical Institute. NR 42 TC 56 Z9 58 U1 3 U2 9 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD OCT PY 2012 VL 22 IS 10 BP 1864 EP 1876 DI 10.1101/gr.133751.111 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 013SJ UT WOS:000309325900004 PM 22948768 ER PT J AU Kulich, RJ Stone, M AF Kulich, Ronald J. Stone, Melissa TI Risk Stratification With Opioid Therapy SO HEADACHE LA English DT Article DE opioid; risk; assessment; headache ID REFRACTORY DAILY HEADACHE; CHRONIC NONCANCER PAIN; PRACTICE GUIDE; PRESCRIPTION; MANAGEMENT; TRENDS; ABUSE; TROUP; ANALGESICS; VALIDATION AB The use of chronic opioid therapy for persistent headache remains controversial because of limited supporting data and potential risks. In addition to possible individual risks for the patient, society risks associated with diversion and substance abuse are well documented. Few studies directly address risk stratification for opioid therapy where a diagnosis of headache is present, making it necessary to extrapolate from other pain research when developing recommendations for screening and patient management. Considering the historical framework of opioid prescribing, relevant studies assessing risk stratification of chronic opioid therapy are reviewed. Specific risk factors that may lead to a problematic course with chronic opioid therapy are outlined. Both clinical experience and the limited empirical research underscore the need for multiple assessment tools and ongoing patient monitoring in the evaluation of these risk factors. C1 [Kulich, Ronald J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Pain Med,Pain Ctr, Boston, MA 02129 USA. [Kulich, Ronald J.] Tufts Univ, Sch Dent Med, Boston, MA 02111 USA. [Stone, Melissa] Massachusetts Sch Profess Psychol, Boston, MA USA. RP Kulich, RJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Pain Med,Pain Ctr, 3rd Floor,Wang Bldg, Boston, MA 02129 USA. NR 38 TC 0 Z9 0 U1 1 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-8748 J9 HEADACHE JI Headache PD OCT PY 2012 VL 52 SU 2 SI SI BP 88 EP 93 DI 10.1111/j.1526-4610.2012.02236.x PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 015LI UT WOS:000309447000008 PM 23030538 ER PT J AU Underhill, ML Kiviniemi, MT AF Underhill, Meghan L. Kiviniemi, Marc T. TI The Association of Perceived Provider-Patient Communication and Relationship Quality With Colorectal Cancer Screening SO HEALTH EDUCATION & BEHAVIOR LA English DT Article DE cancer prevention and screening; health communications; health promotion; patient education; quantitative methods ID NATIONAL TRENDS SURVEY; CONSUMER ASSESSMENT; UNITED-STATES; SURVEY HINTS; SOCIETY GUIDELINES; HEALTH PLANS; CARE; BARRIERS; ISSUES; ADULTS AB Background. Two-thirds of adults aged 50 years and older are adherent to recommendations for colorectal cancer screening. Provider-patient communication and characteristics of the patient-provider relationship may relate to screening behavior. Methods. The association of provider communication quality, relationship, and colorectal cancer screening was examined within data from the 2007 Health Information National Trends Survey. Results. Perceived provider communication and relationship quality were associated with both adherence to colonoscopy and with ever having been screened. Predictive margins analyses indicated that increasing perceptions from lowest to highest levels of communication and relationship quality would be associated with increases in screening rates approaching 16 percentage points. Conclusion. Improving provider-patient communication and relationship quality could potentially improve colorectal cancer screening behaviors among adults aged 50 years and older. Future research and clinical practice should focus on understanding the role of these factors in screening behavior and enhance the provider-patient interaction. C1 [Underhill, Meghan L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kiviniemi, Marc T.] SUNY Buffalo, Buffalo, NY 14260 USA. RP Underhill, ML (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM meghanl_underhill@dfci.harvard.edu RI Kiviniemi, Marc/B-8513-2013 OI Kiviniemi, Marc/0000-0002-1299-8416 FU NCI NIH HHS [K07CA106225, K07 CA106225] NR 40 TC 15 Z9 15 U1 0 U2 10 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD OCT PY 2012 VL 39 IS 5 BP 555 EP 563 DI 10.1177/1090198111421800 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 014DB UT WOS:000309354200007 PM 21986241 ER PT J AU Yeh, DD Kutcher, ME Knudson, MM Tang, JF AF Yeh, Daniel Dante Kutcher, Matthew E. Knudson, M. Margaret Tang, Julin F. TI Epidural analgesia for blunt thoracic injury-Which patients benefit most? SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE Rib fractures; Epidural analgesia; Blunt thoracic injury ID MULTIPLE RIB FRACTURES; POSTOPERATIVE ANALGESIA; PARAVERTEBRAL INFUSION; ELDERLY-PATIENTS; TRAUMA PATIENTS; PAIN-CONTROL; MORTALITY; MORBIDITY; BUPIVACAINE; THORACOTOMY AB Introduction: Epidural analgesia for blunt thoracic injury has been demonstrated to be beneficial for pulmonary function, analgesia, and subjective pain; however the optimal patient selection and timing of thoracic epidural placement have not been well studied. We hypothesised that early (<48 h) epidural analgesia (EA) as compared with usual care involving oral and intravenous narcotics delivered by patient-controlled analgesia (PCA) in patients with blunt thoracic trauma (>3 ribs fractured) is associated with fewer pulmonary complications and lower resource utilisation as measured by ICU and hospital length of stay. Methods: This is a retrospective review of all non-intubated patients suffering from blunt thoracic injury with 3 or more rib fractures requiring hospital admission for >24 h over a recent 5-year period. Pulmonary complications were defined as pneumonia, empyema, hypoxia, and need for delayed intubation. Logistic regression was utilised to analyse patient and injury characteristics associated with pulmonary complications. Results: 187 patients were included in the analysis; early thoracic epidural was utilised in 18% (n = 34). There was no difference in age, ISS, ICU length of stay (LOS), or pulmonary complications between patients who received an epidural (EPI) compared with those who did not (NO EPI). A significantly increased incidence of pulmonary complications was noted in patients who required tube thoracostomy (p = 0.017). Conclusion: In our experience, insertion of a thoracic epidural catheter early post-injury failed to reduce the incidence of pulmonary complications, ICU and hospital LOS. However, since pulmonary complications are more frequent in patients requiring tube thoracostomy, the cost-effectiveness of epidural analgesia in these patients warrants further investigation. (c) 2012 Elsevier Ltd. All rights reserved. C1 [Yeh, Daniel Dante] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Kutcher, Matthew E.] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Surg, San Francisco, CA 94143 USA. [Knudson, M. Margaret] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Surg, San Francisco, CA 94110 USA. RP Yeh, DD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 165 Cambridge St 810, Boston, MA 02114 USA. EM dyeh2@partners.org; matthew.kutcher@ucsfmedctr.org; pknudson@sfghsurg.ucsf.edu; tangj@anesthesia.ucsf.edu NR 34 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 J9 INJURY JI Injury-Int. J. Care Inj. PD OCT PY 2012 VL 43 IS 10 BP 1667 EP 1671 DI 10.1016/j.injury.2012.05.022 PG 5 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA 014OU UT WOS:000309386200008 PM 22704784 ER PT J AU Merlin, JS Westfall, AO Raper, JL Zinski, A Norton, WE Willig, JH Gross, R Ritchie, CS Saag, MS Mugavero, MJ AF Merlin, Jessica S. Westfall, Andrew O. Raper, James L. Zinski, Anne Norton, Wynne E. Willig, James H. Gross, Robert Ritchie, Christine S. Saag, Michael S. Mugavero, Michael J. TI Pain, Mood, and Substance Abuse in HIV: Implications for Clinic Visit Utilization, Antiretroviral Therapy Adherence, and Virologic Failure SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; pain; psychiatric illness; substance abuse; ART adherence; health care utilization ID OPIOID-PRESCRIBING PRACTICES; HUMAN-IMMUNODEFICIENCY-VIRUS; PATIENT-REPORTED OUTCOMES; PRIMARY-CARE; VIRAL LOAD; PSYCHIATRIC-DISORDERS; DISEASE PROGRESSION; INFECTED PATIENTS; MENTAL-HEALTH; PREVALENCE AB Background: Cooccurring pain, mood disorders, and substance abuse are common in HIV-infected patients. Our objective was to investigate the relationship between pain, alone and in the context of mood disorders and substance abuse, on clinic utilization, antiretroviral therapy adherence, and virologic suppression. Methods: Pain, mood disorders, and substance abuse were assessed at the first visit. No-show and urgent visits were measured over a 1-year period. Models were adjusted for age, race, sex, insurance status, CD4(+) T-lymphocyte count, and HIV risk factor. Results: Among 1521 participants, 509 (34%) reported pain, 239 (16%) had pain alone, 189 (13%) had pain and a mood disorder, and 30 (2%) had pain and substance abuse. In univariate models, participants with pain, mood disorders, and substance abuse had higher odds of a no-show visit than those without these conditions [odds ratio (OR), 1.4; 95% confidence interval (CI), 1.1-1.8; OR, 1.5; 95% CI, 1.2-1.9; OR, 2.0; 95% CI, 1.4-2.8, respectively]. In the multivariable model, pain increased the odds of a no-show visit only in participants without substance abuse (OR, 1.5; 95% CI, 1.1-1.9) and pain reduced the odds of a no-show visit in participants with substance abuse (OR, 0.5; 95% CI, 0.2-0.9; P for interaction = 0.0022). Conclusions: In this study, pain increased the odds of no-show visits but only for participants without substance abuse. Because pain, mood disorders, and substance abuse are highly prevalent in HIV-infected patients, our findings have implications for HIV treatment success. Interventions that incorporate pain management may be important for improving health outcomes in patients living with HIV infection. C1 [Merlin, Jessica S.; Westfall, Andrew O.; Raper, James L.; Zinski, Anne; Willig, James H.; Saag, Michael S.; Mugavero, Michael J.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. [Merlin, Jessica S.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Med, Div Gerontol Geriatr & Palliat Care, Birmingham, AL 35294 USA. [Westfall, Andrew O.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Biostat, Birmingham, AL 35294 USA. [Norton, Wynne E.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Hlth Behav, Birmingham, AL 35294 USA. [Gross, Robert] Univ Penn, Dept Med, Div Infect Dis, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Gross, Robert] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Ritchie, Christine S.] Univ Calif San Francisco, Dept Med, Div Geriatr, Jewish Home San Francisco Ctr Res Aging, San Francisco, CA USA. RP Merlin, JS (reprint author), BBRB 222,1530 3rd Ave S, Birmingham, AL 35294 USA. EM jmerlin@uab.edu OI Westfall, Andrew/0000-0002-0468-4695 FU Definicaire LLC.; Penn Center for AIDS Research (CFAR) [P30 AI 045008]; NIA [7K07AG031779]; Merck Foundation; Bristol-Myers Squibb; Gilead Sciences; Tibotec Therapeutics; Pfizer, Inc; Definicare, LLC.; [K23MH082641] FX A. O. Westfall has received consulting fees from Definicaire LLC. R. Gross is supported by the Penn Center for AIDS Research (CFAR) (P30 AI 045008). C. S. Ritchie is supported by 7K07AG031779 (NIA). M. J. Mugavero is supported by K23MH082641 and has received consulting fees (advisory board) from Merck Foundation, Bristol-Myers Squibb, and Gilead Sciences, and grant support to UAB from Tibotec Therapeutics, Pfizer, Inc, Bristol-Myers Squibb, and Definicare, LLC. For the remaining authors, no conflicts of interest were disclosed. NR 62 TC 31 Z9 31 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD OCT 1 PY 2012 VL 61 IS 2 BP 164 EP 170 DI 10.1097/QAI.0b013e3182662215 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 012EQ UT WOS:000309218700013 PM 22766967 ER PT J AU Korthuis, PT Fiellin, DA McGinnis, KA Skanderson, M Justice, AC Gordon, AJ Doebler, DA Asch, SM Fiellin, LE Bryant, K Gibert, CL Crystal, S Goetz, MB Rimland, D Rodriguez-Barradas, MC Kraemer, KL AF Korthuis, P. Todd Fiellin, David A. McGinnis, Kathleen A. Skanderson, Melissa Justice, Amy C. Gordon, Adam J. Doebler, Donna Almario Asch, Steven M. Fiellin, Lynn E. Bryant, Kendall Gibert, Cynthia L. Crystal, Stephen Goetz, Matthew Bidwell Rimland, David Rodriguez-Barradas, Maria C. Kraemer, Kevin L. TI Unhealthy Alcohol and Illicit Drug Use Are Associated With Decreased Quality of HIV Care SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE alcohol; quality of health care; HIV; quality indicators; health care; opioid-related disorders ID HUMAN-IMMUNODEFICIENCY-VIRUS; SUBSTANCE-ABUSE TREATMENT; ACTIVE ANTIRETROVIRAL THERAPY; HEALTH-CARE; UNITED-STATES; OF-CARE; TREATMENT OUTCOMES; PERFORMANCE-MEASURES; INFECTED PERSONS; MEDICAL-CARE AB Background: HIV-infected patients with substance use experience suboptimal health outcomes, possibly because of variations in care. Objectives: To assess the association between substance use and the quality of HIV care (QOC) received. Research Design: Retrospective cohort study. Subjects: HIV-infected patients enrolled in the Veterans Aging Cohort Study. Measures: We collected self-report substance use data and abstracted 9 HIV quality indicators (QIs) from medical records. Independent variables were unhealthy alcohol use (AUDIT-C score >= 4) and illicit drug use (self-report of stimulants, opioids, or injection drug use in past year). Main outcome was the percentage of QIs received, if eligible. We estimated associations between substance use and QOC using multivariable linear regression. Results: The majority of the 3410 patients were male (97.4%) and black (67.0%) with a mean age of 49.1 years (SD = 8.8). Overall, 25.8% reported unhealthy alcohol use, 22% illicit drug use, and participants received 81.5% (SD - 18.9) of QIs. The mean percentage of QIs received was lower for those with unhealthy alcohol use versus not (59.3% vs. 70.0%, P < 0.001) and those using illicit drugs vs. not (57.8% vs. 70.7%, P < 0.001). In multivariable models, unhealthy alcohol use (adjusted beta -2.74; 95% confidence interval: -4.23 to -1.25) and illicit drug use (adjusted beta -3.51; 95% CI: -4.99 to -2.02) remained inversely associated with the percentage of QIs received. Conclusions: Although the overall QOC for these HIV-infected Veteran patients was high, gaps persist for those with unhealthy alcohol and illicit drug use. Interventions that address substance use in HIV-infected patients may improve the QOC received. C1 [Korthuis, P. Todd] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA. [Korthuis, P. Todd] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA. [Fiellin, David A.; Justice, Amy C.; Fiellin, Lynn E.] Yale Univ, Sch Med, Dept Gen Med, New Haven, CT USA. [Fiellin, David A.; Justice, Amy C.; Fiellin, Lynn E.] Yale Univ, Sch Med, Dept Publ Hlth, Div Gen Internal Med, New Haven, CT 06510 USA. [Fiellin, David A.; Justice, Amy C.; Fiellin, Lynn E.] Yale Univ, Sch Med, Ctr Interdisciplinary Res AIDS, New Haven, CT USA. [McGinnis, Kathleen A.; Skanderson, Melissa; Gordon, Adam J.; Doebler, Donna Almario] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Justice, Amy C.] VA Connecticut Healthcare Syst, Vet Aging Cohort Study Coordinating Ctr, Dept Gen Med, West Haven, CT USA. [Justice, Amy C.] VA Connecticut Healthcare Syst, Vet Aging Cohort Study Coordinating Ctr, Dept Publ Hlth, West Haven, CT USA. [Gordon, Adam J.; Doebler, Donna Almario; Kraemer, Kevin L.] Univ Pittsburgh, Dept Med, Ctr Res Hlth Care, Pittsburgh, PA USA. [Asch, Steven M.] Stanford Univ, VA Greater Palo Alto Healthcare Syst, Palo Alto, CA 94304 USA. [Bryant, Kendall] NIAAA, HIV AIDS Res, Rockville, MD 20852 USA. [Gibert, Cynthia L.] VA Med Ctr, Washington, DC USA. [Gibert, Cynthia L.] George Washington Univ, Med Ctr, Washington, DC 20037 USA. [Crystal, Stephen] Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, New Brunswick, NJ 08903 USA. [Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA 90095 USA. [Rimland, David] VA Med Ctr, Dept Med, Atlanta, GA USA. [Rimland, David] Emory Univ, Sch Med, Atlanta, GA USA. [Rodriguez-Barradas, Maria C.] Michael E DeBakey VA Med Ctr, Dept Med, Infect Dis Sect, Houston, TX USA. [Rodriguez-Barradas, Maria C.] Baylor Coll Med, Houston, TX 77030 USA. RP Korthuis, PT (reprint author), Oregon Hlth & Sci Univ, Dept Med, 3181 SW Sam Jackson Pk Rd,Mail Code L-475, Portland, OR 97239 USA. EM korthuis@ohsu.edu OI Goetz, Matthew/0000-0003-4542-992X; Fiellin, David/0000-0002-4006-010X FU National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism [U10AA013566]; National Institutes of Health, National Institute on Drug Abuse [K23 DA019809] FX Supported by the National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism Grant U10AA013566; National Institutes of Health, National Institute on Drug Abuse Grant K23 DA019809 (to Dr Korthuis). NR 53 TC 12 Z9 12 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD OCT 1 PY 2012 VL 61 IS 2 BP 171 EP 178 DI 10.1097/QAI.0b013e31826741aa PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 012EQ UT WOS:000309218700014 PM 22820808 ER PT J AU Weiser, SD Gupta, R Tsai, AC Frongillo, EA Grede, N Kumbakumba, E Kawuma, A Hunt, PW Martin, JN Bangsberg, DR AF Weiser, Sheri D. Gupta, Reshma Tsai, Alexander C. Frongillo, Edward A. Grede, Nils Kumbakumba, Elias Kawuma, Annet Hunt, Peter W. Martin, Jeffrey N. Bangsberg, David R. TI Changes in Food Insecurity, Nutritional Status, and Physical Health Status After Antiretroviral Therapy Initiation in Rural Uganda SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE food insecurity; antiretroviral treatment; HIV; Uganda; nutrition; physical health status ID QUALITY-OF-LIFE; HIV-INFECTED INDIVIDUALS; PERCEIVED PERSONAL DISPARITY; SOUTH-AFRICAN HOUSEHOLDS; DAR-ES-SALAAM; SOCIAL SUPPORT; MEDICAL OUTCOMES; ECONOMIC-IMPACT; SAN-FRANCISCO; HIV/AIDS AB Objective: To investigate whether time on antiretroviral therapy (ART) is associated with improvements in food security and nutritional status, and the extent to which associations are mediated by improved physical health status. Design: The Uganda AIDS Rural Treatment Outcomes study, a prospective cohort of HIV-infected adults newly initiating ART in Mbarara, Uganda. Methods: Participants initiating ART underwent quarterly structured interview and blood draws. The primary explanatory variable was time on ART, constructed as a set of binary variables for each 3-month period. Outcomes were food insecurity, nutritional status, and PHS. We fit multiple regression models with cluster-correlated robust estimates of variance to account for within-person dependence of observations over time, and analyses were adjusted for clinical and sociodemographic characteristics. Results: Two hundred twenty-eight ART-naive participants were followed for up to 3 years, and 41% were severely food insecure at baseline. The mean food insecurity score progressively declined (test for linear trend P < 0.0001), beginning with the second quarter (b = -1.6; 95% confidence interval: -2.7 to -0.45) and ending with the final quarter (b = -6.4; 95% confidence interval: -10.3 to -2.5). PHS and nutritional status improved in a linear fashion over study follow-up (P < 0.001). Inclusion of PHS in the regression model attenuated the relationship between ART duration and food security. Conclusions: Among HIV-infected individuals in Uganda, food insecurity decreased and nutritional status and PHS improved over time after initiation of ART. Changes in food insecurity were partially explained by improvements in PHS. These data support early initiation of ART in resource-poor settings before decline in functional status to prevent worsening food insecurity and its detrimental effects on HIV treatment outcomes. C1 [Weiser, Sheri D.; Hunt, Peter W.] Univ Calif San Francisco, Div HIV AIDS, San Francisco Gen Hosp, Dept Med, San Francisco, CA 94110 USA. [Gupta, Reshma] Univ Washington, Dept Internal Med, Sch Med, Seattle, WA USA. [Tsai, Alexander C.] Harvard Univ, Robert Wood Johnson Hlth & Soc Scholars Program, Cambridge, MA 02138 USA. [Tsai, Alexander C.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Frongillo, Edward A.] Univ S Carolina, Arnold Sch Publ Hlth, Dept Hlth Promot Educ & Behav, Columbia, SC 29208 USA. [Grede, Nils] United Nations World Food Programme, Rome, Italy. [Kumbakumba, Elias; Kawuma, Annet; Bangsberg, David R.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Martin, Jeffrey N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Bangsberg, David R.] MIT, Ragon Inst MGH, Boston, MA USA. [Bangsberg, David R.] Harvard Univ, Boston, MA 02115 USA. RP Weiser, SD (reprint author), Univ Calif San Francisco, Div HIV AIDS, San Francisco Gen Hosp, Dept Med, POB 0874, San Francisco, CA 94110 USA. EM sheri.weiser@ucsf.edu OI Tsai, Alexander/0000-0001-6397-7917 FU National Institutes of Health [K23 MH079713 MH79713-03S1, R01 MH54907, P30 AI27763]; Tim and Jane Meyer Family Foundation; World Food Programme; Burke Family Foundation; Robert Wood Johnson Health and Society Scholars Program; [K24 MH87227] FX Supported by National Institutes of Health Grants K23 MH079713 MH79713-03S1, R01 MH54907, P30 AI27763 (UCSF-Gladstone Institute Center for AIDS Research), and the Tim and Jane Meyer Family Foundation. Additional funding for study analyses was provided by the World Food Programme. The authors acknowledge the following additional sources of salary support: the Burke Family Foundation (to Dr S. D. Weiser), K24 MH87227 (to Dr D. R. Bangsberg), and the Robert Wood Johnson Health and Society Scholars Program (to Dr. A. C. Tsai). NR 67 TC 18 Z9 19 U1 3 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD OCT 1 PY 2012 VL 61 IS 2 BP 179 EP 186 DI 10.1097/QAI.0b013e318261f064 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 012EQ UT WOS:000309218700015 PM 22692093 ER PT J AU Winter, L Parks, SM AF Winter, Laraine Parks, Susan M. TI Elders' Preferences for Life-Prolonging Treatment and Their Proxies' Substituted Judgment: Influence of the Elders' Current Health SO JOURNAL OF AGING AND HEALTH LA English DT Article DE end of life; families; physical function ID SURROGATE DECISION-MAKING; SUSTAINING MEDICAL TREATMENTS; OF-LIFE; ADVANCE DIRECTIVES; PROSPECT-THEORY; OLDER-ADULTS; GENDER-DIFFERENCES; END; ACCURACY; CARE AB Objectives: People in poor health tend to view life-prolonging treatments (e.g., tube feeding) as more acceptable than do healthier people. Do proxies' substituted judgments reveal a similar tendency, showing greater acceptance when the elder is in worse health? Method: In a cross-sectional telephone-based survey of 202 elderly individuals and their proxies, preferences for 4 life-prolonging treatments in 7 health prospects were examined in relation to the elder's current health status, operationalized as number of deficits in activities of daily living. Results: Stronger preferences for life-prolonging treatments in worse-health prospects were expressed by both elders and proxies when the elders' current health was relatively poor. The interaction effect was at least as pronounced for proxies' substituted judgment as for elders' own preferences. Discussion: Findings provide important insight into proxy decision making and have particular implications for proxy decision making on behalf of elders with dementia or other causes of decisional incapacity. C1 [Winter, Laraine; Parks, Susan M.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. RP Winter, L (reprint author), Philadelphia VA Med Ctr, 3900 Woodland Ave,Room B904, Philadelphia, PA 19104 USA. EM laraine.winter@gmail.com FU NINR NIH HHS [R21NR010263] NR 55 TC 3 Z9 3 U1 7 U2 16 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0898-2643 J9 J AGING HEALTH JI J. Aging Health PD OCT PY 2012 VL 24 IS 7 BP 1157 EP 1178 DI 10.1177/0898264312454572 PG 22 WC Gerontology; Health Policy & Services SC Geriatrics & Gerontology; Health Care Sciences & Services GA 007IV UT WOS:000308882900004 PM 22869900 ER PT J AU Baliram, R Sun, L Cao, J Li, JH Latif, R Huber, AK Yuen, T Blair, HC Zaidi, M Davies, TF AF Baliram, Ramkumarie Sun, Li Cao, Jay Li, Jianhua Latif, Rauf Huber, Amanda K. Yuen, Tony Blair, Harry C. Zaidi, Mone Davies, Terry F. TI Hyperthyroid-associated osteoporosis is exacerbated by the loss of TSH signaling SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID THYROID-STIMULATING HORMONE; BONE-MINERAL DENSITY; SERUM TSH; POSTMENOPAUSAL WOMEN; THYROXINE THERAPY; RECOMBINANT TSH; OSTEOPROTEGERIN; POLYMORPHISM; FRACTURES; REGULATOR AB The osteoporosis associated with human hyperthyroidism has traditionally been attributed to elevated thyroid hormone levels. There is evidence, however, that thyroid-stimulating hormone (TSH), which is low in most hyperthyroid states, directly affects the skeleton. Importantly, Tshr-knockout mice are osteopenic. In order to determine whether low TSH levels contribute to bone loss in hyperthyroidism, we compared the skeletal phenotypes of wild-type and Tshr-knockout mice that were rendered hyperthyroid. We found that hyperthyroid mice lacking TSHR had greater bone loss and resorption than hyperthyroid wild-type mice, thereby demonstrating that the absence of TSH signaling contributes to bone loss. Further, we identified a TSH-like factor that may confer osteoprotection. These studies suggest that therapeutic suppression of TSH to very low levels may contribute to bone loss in people. C1 [Sun, Li; Li, Jianhua; Yuen, Tony; Zaidi, Mone] Mt Sinai Sch Med, Mt Sinai Bone Program, Dept Med, New York, NY 10029 USA. [Sun, Li; Li, Jianhua; Yuen, Tony; Zaidi, Mone] James J Peters VA Med Ctr, New York, NY USA. [Baliram, Ramkumarie; Latif, Rauf; Huber, Amanda K.; Davies, Terry F.] Mt Sinai Sch Med, Thyroid Res Unit, New York, NY 10029 USA. [Cao, Jay] ARS, USDA, Human Nutr Res Ctr, Grand Forks, ND USA. [Blair, Harry C.] Univ Pittsburgh, Dept Pathol & Cell Biol, Pittsburgh, PA USA. [Blair, Harry C.] Pittsburgh VA Med Ctr, Pittsburgh, PA USA. RP Zaidi, M (reprint author), Mt Sinai Sch Med, Mt Sinai Bone Program, Dept Med, Box 1050,1 Gustave L Levy Pl, New York, NY 10029 USA. EM mone.zaidi@mssm.edu FU NIH [DK080459, DK069713, DK052464, AG23186, DK70526]; VA Merit Review Program; USDA ARS CRIS Program [5450-51000-046-00D] FX This work was supported in part by DK080459 (to M. Zaidi, L. Sun, and T.F. Davies), DK069713 and DK052464 (to T.F. Davies), and AG23186 and DK70526 (to M. Zaidi) from the NIH and by the VA Merit Review Program (to T.F. Davies and H.C. Blair). J. Cao is supported by the USDA ARS CRIS Program (5450-51000-046-00D). NR 32 TC 32 Z9 34 U1 2 U2 10 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2012 VL 122 IS 10 BP 3737 EP 3741 DI 10.1172/JCI63948 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 013VK UT WOS:000309333800042 PM 22996689 ER PT J AU Karlin, BE Brown, GK Trockel, M Cunning, D Zeiss, AM Taylor, CB AF Karlin, Bradley E. Brown, Gregory K. Trockel, Mickey Cunning, Darby Zeiss, Antonette M. Taylor, C. Barr TI National Dissemination of Cognitive Behavioral Therapy for Depression in the Department of Veterans Affairs Health Care System: Therapist and Patient-Level Outcomes SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE dissemination; cognitive behavioral therapy; depression; psychotherapy training; veterans ID POSTTRAUMATIC-STRESS-DISORDER; WORKING ALLIANCE INVENTORY; PSYCHOMETRIC PROPERTIES; ANTIDEPRESSANT MEDICATION; PSYCHOLOGICAL TREATMENTS; MOOD DISORDERS; COMPETENCE; TRIAL; COMORBIDITY; SCALE AB Objective: The Department of Veterans Affairs (VA) health care system is nationally disseminating and implementing cognitive behavioral therapy for depression (CBT-D). The current article evaluates therapist and patient-level outcomes associated with national training in and implementation of CBT-D in the VA health care system. Method: Therapist competencies were assessed with the Cognitive Therapy Rating Scale (CTRS). Patient outcomes were assessed with the Beck Depression Inventory-II and the World Health Organization Quality of Life-BREF. Therapeutic alliance was assessed with the Working Alliance Inventory -Short Revised. Two-hundred twenty-one therapists have received training, and 356 veteran patients have received treatment through the VA CBT-D Training Program. Results: Of therapists who have participated in the program, 182 (82%) completed all training requirements and achieved competency, reflected by a score of 40 on the CTRS. Of 356 patients, nearly 70% completed 10 or more sessions or improved sufficiently to stop therapy before the 10th session. Mean depression scores decreased by approximately 40% from initial to later treatment phase. Effect sizes of changes ranged from d = 0.39 to d = 0.74 for quality of life and from d = 0.47 to d = 0.66 for therapeutic alliance measures. Conclusion: National training in and implementation of CBT-D within the VA health care system is associated with significant, positive therapist training outcomes, as evidenced by increases in CBT core competencies. The implementation of the protocol by newly trained CBT-D therapists is associated with significantly improved patient outcomes, as evidenced by large decreases in depression and improvements in quality of life. C1 [Karlin, Bradley E.; Zeiss, Antonette M.] US Dept Vet Affairs Cent Off, Off Mental Hlth Serv, Washington, DC 20420 USA. [Brown, Gregory K.] Philadelphia Vet Affairs Med Ctr, VISN Mental Illness Res Educ & Clin Ctr 4, Philadelphia, PA USA. [Brown, Gregory K.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Trockel, Mickey; Cunning, Darby; Taylor, C. Barr] Stanford Univ, Med Ctr, Dept Psychiat, Palo Alto, CA 94304 USA. [Trockel, Mickey; Cunning, Darby; Taylor, C. Barr] Vet Affairs Palo Alto Hlth Care Syst, Sierra Pacific Mental Illness Res Educ & Clin Ctr, Palo Alto, CA USA. RP Karlin, BE (reprint author), US Dept Vet Affairs Cent Off, Off Mental Hlth Serv 10P4M, 810 Vermont Ave NW, Washington, DC 20420 USA. EM bradley.karlin2@va.gov NR 71 TC 39 Z9 39 U1 1 U2 18 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD OCT PY 2012 VL 80 IS 5 BP 707 EP 718 DI 10.1037/a0029328 PG 12 WC Psychology, Clinical SC Psychology GA 013NP UT WOS:000309312400001 PM 22823859 ER PT J AU Morgenstern, J Kuerbis, AN Chen, AC Kahler, CW Bux, DA Kranzler, HR AF Morgenstern, Jon Kuerbis, Alexis N. Chen, Andrew C. Kahler, Christopher W. Bux, Donald A., Jr. Kranzler, Henry R. TI A Randomized Clinical Trial of Naltrexone and Behavioral Therapy for Problem Drinking Men Who Have Sex With Men SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article DE problem drinkers; men who have sex with men; naltrexone; cognitive-behavior therapy; moderation ID PLACEBO-CONTROLLED TRIAL; SUBSTANCE USE DISORDERS; ALCOHOL DEPENDENCE; PROBLEM DRINKERS; MOTIVATIONAL ENHANCEMENT; TARGETED NALTREXONE; ABUSE TREATMENT; HIV-INFECTION; DOUBLE-BLIND; DRUG-USE AB Objective: This study tested the comparative effectiveness of modified behavioral self-control therapy (MBSCT) and naltrexone (NIX), as well as the added benefit of combining the 2, in problem drinking men who have sex with men (MSM) seeking to reduce but not quit drinking. Method: Participants (N = 200) were recruited and urn randomized to 1 of 2 medication conditions, NTX or placebo (PBO), and either MSBCT or no behavioral intervention, yielding 4 conditions: PBO, NTX, MSBCT, and NIX + MSBCT. In addition, all participants received a brief medication compliance intervention. Participants were treated for 12 weeks and assessed 1 week after treatment completion. Two primary outcomes-sum of standard drinks and number of heavy drinking days and 1 secondary outcome percentage of those drinking in a nonhazardous manner (NoH)-were selected a priori. Results: There was a significant main effect for MBSCT (all ps < .01) but not NTX on all 3 outcomes. In addition, the combination of NTX and MBSCT was not more effective than either MSCBT or PBO. There was a significant interaction effect on NoH, such that NIX significantly increased the likelihood (odds ratio = 3.3) of achieving a nonhazardous drinking outcome relative to PBO. In addition, NIX was significantly more effective than PBO on a descriptive outcome: negative consequences of drinking. Conclusions: There was no advantage to adding NIX to MBSCT. In addition, MBSCT showed stronger evidence of efficacy than NIX. At the same time, NIX delivered in the context of a minimal medication compliance intervention was significantly more effective than PBO on an important clinical indicator. Results provide new information to guide the treatment of problem drinking, including in primary care settings. C1 [Morgenstern, Jon; Kuerbis, Alexis N.; Chen, Andrew C.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. [Kahler, Christopher W.] Brown Univ, Dept Behav & Social Sci, Providence, RI 02912 USA. [Kahler, Christopher W.] Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. [Kranzler, Henry R.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kranzler, Henry R.] Philadelphia VA Med Ctr, MIRECC VISN4, Philadelphia, PA USA. RP Morgenstern, J (reprint author), Columbia Univ, Coll Phys & Surg, Dept Psychiat, 180 Ft Washington Ave,HP-240, New York, NY 10032 USA. EM jm977@columbia.edu FU NIAAA NIH HHS [5 RO1 AA015553, K24 AA013736, K23 AA018696, R01 AA015553] NR 65 TC 14 Z9 14 U1 4 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD OCT PY 2012 VL 80 IS 5 BP 863 EP 875 DI 10.1037/a0028615 PG 13 WC Psychology, Clinical SC Psychology GA 013NP UT WOS:000309312400015 PM 22612306 ER PT J AU Gorman, A Kaye, EK Nunn, M Garcia, RI AF Gorman, A. Kaye, E. K. Nunn, M. Garcia, R. I. TI Changes in Body Weight and Adiposity Predict Periodontitis Progression in Men SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE overweight; obesity; body mass index; waist circumference; adiposity; periodontal disease ID EXAMINER AGREEMENT; RISK INDICATORS; DISEASE; OBESITY; ADULTS; ASSOCIATION; OVERWEIGHT; HEALTH; YOUNG AB Most studies linking obesity and periodontal disease have been cross-sectional in design. We examined whether gains in body weight, waist circumference, and arm fat area are associated with periodontitis progression in 893 non-diabetic men followed for up to four decades in the prospective VA Dental Longitudinal Study. Probing pocket depth (PPD) was measured by calibrated examiners. Repeated-measures generalized linear models estimated the mean cumulative numbers of teeth with PPD events (PPD > 3 mm) at each dental examination and the slopes associated with increasing numbers of affected teeth over time. Means were adjusted for baseline PPD, education, and cigarette pack-years, and time-dependent values of age, mean plaque score, cigarette packs/day, brushing, and flossing. Men who were overweight at baseline and gained weight most rapidly (> 0.19 kg/yr or similar to 15 lb during follow-up) had significantly more PPD events than men in the lowest tertile of weight gain (<= -0.05 kg/yr). Overweight men whose waist circumference increased > 0.14-0.39 or > 0.39 cm/yr experienced more PPD events than men in the lowest tertile (<= 0.14 cm/yr). Increase in arm fat area was associated with disease progression in normal-weight men. These results suggest that tracking adiposity changes with easily obtained anthropometric measures may help predict risk of periodontitis progression. C1 [Gorman, A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Kaye, E. K.; Garcia, R. I.] Boston Univ, Henry M Goldman Sch Dent Med, Dept Hlth Policy & Hlth Serv Res, Boston, MA 02215 USA. [Nunn, M.] Creighton Univ, Sch Dent, Dept Periodont, Omaha, NE 68178 USA. [Garcia, R. I.] VA Boston Healthcare Syst, Boston, MA USA. RP Gorman, A (reprint author), Boston Univ, Sch Med, 72 E Concord St, Boston, MA 02118 USA. EM ago-rman@Lifespan.org OI Garcia, Raul/0000-0003-2153-4629; Kaye, Elizabeth/0000-0001-7529-2501 FU National Institute of Dental and Craniofacial Research [R01 DE019833, K24 DE00419]; US Department of Veterans Affairs; VA HSRD Service FX This work was supported by National Institute of Dental and Craniofacial Research R01 DE019833 and K24 DE00419. The Dental Longitudinal Study and Normative Aging Study are components of the Massachusetts Veterans Epidemiology Research and Information Center, which is supported by the US Department of Veterans Affairs Cooperative Studies Program. Dr. Garcia was a recipient of a Veterans Affairs Career Development Award in Health Services Research from the VA HSRD Service. Views expressed in this paper are those of the authors and do not necessarily represent the views of the US Department of Veterans Affairs. The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. NR 23 TC 14 Z9 14 U1 1 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD OCT PY 2012 VL 91 IS 10 BP 921 EP 926 DI 10.1177/0022034512457372 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 007HH UT WOS:000308878900005 PM 22895511 ER PT J AU Shaddox, LM Huang, H Lin, T Hou, W Harrison, PL Aukhil, I Walker, CB Klepac-Ceraj, V Paster, BJ AF Shaddox, L. M. Huang, H. Lin, T. Hou, W. Harrison, P. L. Aukhil, I. Walker, C. B. Klepac-Ceraj, V. Paster, B. J. TI Microbiological Characterization in Children with Aggressive Periodontitis SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE localized aggressive periodontitis; diagnosis; microbiology; Aggregatibacter actinomycetemcomitans; HOMIM; subgingival microbiota ID HIGHLY TOXIC CLONE; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; JUVENILE PERIODONTITIS; PERIODONTOPATHIC BACTERIA; PREVALENCE; CLASSIFICATION; IDENTIFICATION; SEROTYPES; THERAPY; MARKERS AB The objective of this study was to characterize the subgingival microbiota of African-American children with Localized Aggressive Periodontitis (LAP). Fifty-one children were included. Subgingival plaque samples were taken from diseased (DD) and healthy sites (DH) in LAP and from healthy sites in HS and HC and analyzed by 16S rRNA-based microarrays. Aggregatibacter actinomycetemcomitans (Aa) was the only species found to be both more prevalent (OR = 8.3, p = 0.0025) and abundant (p < 0.01) in DD. Filifactor alocis (Fa) was also found to be more prevalent in DD (OR 2.31, CI 1.06-5.01, p = 0.03). Most prevalent species in healthy sites were Selenomonas spp, Veillonella spp, Streptococcus spp, Bergeyella sp, and Kingella oralis. Overall, Streptococcus spp, Campylobacter gracilis, Capnocytophaga granulosa, Haemophilus parainfluenzae, and Lautropia mirabilis were most abundant in healthy children, while Aa, Fa, Tannerella sp, Solobacterium moorei, Parvimonas micra, and Capnocytophaga sp were most abundant in LAP. Based on a comprehensive analysis with 16S rRNA-based microarrays, Aa was strongly associated and site-specific in LAP. In contrast, other species were found to be associated with healthy sites and individuals (ClinicalTrials.gov number CT01330719). C1 [Shaddox, L. M.; Huang, H.; Harrison, P. L.; Aukhil, I.] Univ Florida, Coll Dent, Dept Periodontol, Gainesville, FL 32610 USA. [Lin, T.; Hou, W.] St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38105 USA. [Walker, C. B.] Univ Florida, Coll Dent, Dept Oral Biol, Gainesville, FL 32610 USA. [Paster, B. J.] Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. [Klepac-Ceraj, V.; Paster, B. J.] Forsyth Inst, Cambridge, MA USA. RP Shaddox, LM (reprint author), Univ Florida, Coll Dent, Dept Periodontol, Gainesville, FL 32610 USA. EM lshad-dox@dental.ufl.edu RI Lin, Tong/G-4105-2012; OI Klepac-Ceraj, Vanja/0000-0001-5387-5706; Harrison, Peter/0000-0001-7526-4834 FU NIH/NIDCR [R01DE019456] FX The authors thank the doctors and staff in Leon County Dental Clinic for their assistance in coordinating our visits to the clinic, patient care, and their dental needs. We acknowledge financial support of NIH/NIDCR (R01DE019456). The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. NR 30 TC 33 Z9 35 U1 0 U2 16 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD OCT PY 2012 VL 91 IS 10 BP 927 EP 933 DI 10.1177/0022034512456039 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 007HH UT WOS:000308878900006 PM 22863892 ER PT J AU Beniash, E Simmer, JP Margolis, HC AF Beniash, E. Simmer, J. P. Margolis, H. C. TI Structural Changes in Amelogenin upon Self-assembly and Mineral Interactions SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE enamel; hydroxyapatite; protein self-assembly; protein-mineral interactions; biomineralization; intrinsically disordered protein ID IN-VITRO; CONFORMATIONAL-CHANGES; SECONDARY STRUCTURE; PROTEIN ADSORPTION; ENAMEL MATRIX; NANOSPHERES; BIOMINERALIZATION; ORGANIZATION; AGGREGATION; SURFACES AB Amelogenin, the major protein of forming dental enamel, plays a crucial role in the biomineralization of this tissue. Amelogenin is soluble at low pH and self-assembles to form higher order structures at physiological pH. To understand the mechanisms of its assembly and interactions with calcium phosphate mineral, we conducted FTIR spectroscopy (FTIRS) studies of pH-triggered assembly of recombinant porcine amelogenin rP172 and its interactions with mature hydroxyapatite and apatitic mineral formed in situ. Analysis of our data indicated that rP172 at pH 3.0 exists in an unfolded disordered state, while increases in pH led to structural ordering, manifested by increases in intra- and intermolecular beta-sheet structures and a decrease in random coil and beta-turns. Amelogenin assembled at pH 7.2 was also found to contain large portions of extended intramolecular beta-sheet and PPII. These FTIRS findings are consistent with those previously obtained with other techniques, thus verifying the validity of our experimental approach. Interestingly, interactions with mineral led to a reduction in protein structural organization. The findings obtained show that amelogenin has intrinsic structural flexibility to accommodate interactions with both forming and mature calcium phosphate mineral phases, providing new insights into the potential importance of amelogenin-mineral interactions in enamel biomineralization. C1 [Beniash, E.] Univ Pittsburgh, Sch Dent Med, Dept Oral Biol,Swanson Sch Engn, Ctr Craniofacial Regenerat,McGowan Inst Regenerat, Pittsburgh, PA 15261 USA. [Simmer, J. P.] Univ Michigan, Sch Dent, Ann Arbor, MI 48109 USA. [Margolis, H. C.] Forsyth Inst, Dept Biomineralizat, Cambridge, MA USA. RP Beniash, E (reprint author), Univ Pittsburgh, Sch Dent Med, Dept Oral Biol,Swanson Sch Engn, Ctr Craniofacial Regenerat,McGowan Inst Regenerat, 589 Salk Hall,3501 Terrace St, Pittsburgh, PA 15261 USA. EM ebeniash@pitt.edu FU NIH [R01DE016376] FX This work was supported by the NIH (grant R01DE016376 to H. C. M.). The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. NR 32 TC 15 Z9 15 U1 1 U2 32 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD OCT PY 2012 VL 91 IS 10 BP 967 EP 972 DI 10.1177/0022034512457371 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 007HH UT WOS:000308878900012 PM 22933608 ER PT J AU Tavares, WLF de Brito, LCN Henriques, LCF Teles, FRF Teles, RP Vieira, LQ Sobrinho, APR AF Fonseca Tavares, Warley Luciano Neves de Brito, Luciana Carla Feitosa Henriques, Luiz Carlos Teles, Flavia Rocha Fonseca Teles, Ricardo Palmier Vieira, Leda Quercia Ribeiro Sobrinho, Antonio Paulino TI Effects of Calcium Hydroxide on Cytokine Expression in Endodontic Infections SO JOURNAL OF ENDODONTICS LA English DT Article DE Calcium hydroxide; cytokine expression; root canal infection ID ROOT-CANAL INSTRUMENTATION; NECROSIS-FACTOR-ALPHA; PERIAPICAL GRANULOMAS; APICAL PERIODONTITIS; IN-VITRO; INTERLEUKIN-1-BETA; OBTURATION; LESIONS; CELLS; TEETH AB Introduction: The use of calcium hydroxide is an effective step in killing bacteria that remain after cleaning and shaping procedures. It also induces hard-tissue formation and is effective for stopping inflammatory exudates. Methods: The aim of this study was to assay and to compare the influence of calcium hydroxide on periapical interstitial fluid from human root canals. The mRNA expression levels of the cytokines interferon (IFN)-gamma, tumor necrosis factor-a, interleukin (IL)-1 beta, IL-17A, and IL-10 as well as the chemokine MCP-1 were assayed by real-time polymerase chain reaction immediately after root canal cleaning and 15 days later. Results: Levels of IL-1 beta, IFN-gamma, IL-10, and the chemokine CCL2/MCP-1 were increased in teeth without endodontic dressings. With calcium hydroxide interappointment dressings, no statistically significant changes were observed in cytokine mRNA expression. However, when comparing teeth that received the medication with those that did not, expression levels of IL-1 beta, IFN-gamma, and IL-10 were statistically lower in those teeth that received calcium hydroxide. Conclusions: Analyses of cytokines and the chemokine CCL-2/MCP-1 demonstrated the benefits of calcium hydroxide as a root canal dressing because it impedes the increase of all mediators during the experimental time. (J Endod 2012;38:1368-1371) C1 [Fonseca Tavares, Warley Luciano; Neves de Brito, Luciana Carla; Feitosa Henriques, Luiz Carlos; Ribeiro Sobrinho, Antonio Paulino] Univ Fed Minas Gerais, Sch Dent, BR-30350190 Belo Horizonte, MG, Brazil. [Vieira, Leda Quercia] Univ Fed Minas Gerais, Inst Biol Sci, BR-30350190 Belo Horizonte, MG, Brazil. [Teles, Flavia Rocha Fonseca; Teles, Ricardo Palmier] Forsyth Inst, Dept Periodontol, Boston, MA USA. [Teles, Flavia Rocha Fonseca; Teles, Ricardo Palmier] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Sobrinho, APR (reprint author), Univ Fed Minas Gerais, Sch Dent, R Abre Campo 193,APT 402 Santo, BR-30350190 Belo Horizonte, MG, Brazil. EM sobrinho.bhz@terra.com.br RI 3, INCT/H-4497-2013; Redoxoma, Inct/H-9962-2013; Vieira, Leda/G-7487-2014 FU Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG); Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES); Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) FX Supported by Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG), Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq). NR 38 TC 7 Z9 8 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0099-2399 J9 J ENDODONT JI J. Endod. PD OCT PY 2012 VL 38 IS 10 BP 1368 EP 1371 DI 10.1016/j.joen.2012.06.036 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 014LK UT WOS:000309377000013 PM 22980179 ER PT J AU Wang, VJ Cavagnaro, CS Clark, S Camargo, CA Mansbach, JM AF Wang, Vincent J. Cavagnaro, Christopher S. Clark, Sunday Camargo, Carlos A., Jr. Mansbach, Jonathan M. TI Altitude and Environmental Climate Effects on Bronchiolitis Severity Among Children Presenting to the Emergency Department SO JOURNAL OF ENVIRONMENTAL HEALTH LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; CHILDHOOD ASTHMA; TRACT INFECTIONS; HUMIDITY; TEMPERATURE; ADMISSIONS; HOSPITALIZATION; TRANSMISSION; PARAMETERS; MANAGEMENT AB Bronchiolitis, a respiratory illness, is the leading cause of hospitalization for infants. The authors examined whether environmental factors contributed to the severity of the bronchiolitis illness. They compiled environmental data (temperature, dew point, wind speed, precipitation, altitude, and barometric pressure) to augment clinical data from a 30-center prospective cohort study of emergency department patients with bronchiolitis. They analyzed these data using multivariable logistic regression. Higher altitude was modestly associated with increased retractions (odds ratio [OR] = 1.6; 95% confidence interval [CI] = 1.1-2.1; p < .001) and decreased air entry (OR = 2.0; 95% CI = 1.6-2.6; p < .001). Increasing wind speed had a minor association with more severe retractions (OR = 1.3; 95% CI = 1.1-1.7; p = .02). Higher dew points had a minor association with lower admission rates (OR = 0.9; 95% CI = 0.8-0.996; p = .04). Altitude and environmental climate variables appear to have modest associations with the severity of bronchiolitis in the emergency department. Further studies need to be conducted, however, on limiting exposure to these environmental variables or increasing humidity before making broad recommendations. C1 [Wang, Vincent J.] Childrens Hosp Los Angeles, Div Emergency Med, Los Angeles, CA 90027 USA. [Cavagnaro, Christopher S.] Childrens Hosp Montefiore, Div Pediat Emergency Med, New York, NY USA. [Clark, Sunday] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. [Clark, Sunday] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Mansbach, Jonathan M.] Childrens Hosp Boston, Dept Med, Boston, MA USA. RP Wang, VJ (reprint author), Childrens Hosp Los Angeles, Div Emergency Med, 4650 Sunset Blvd,Mailstop 113, Los Angeles, CA 90027 USA. EM vwang@chla.usc.edu NR 36 TC 4 Z9 4 U1 0 U2 1 PU NATL ENVIRON HEALTH ASSOC PI DENVER PA 720 S COLORADO BLVD SUITE 970, SOUTH TOWER, DENVER, CO 80246 USA SN 0022-0892 J9 J ENVIRON HEALTH JI J. Environ. Health PD OCT PY 2012 VL 75 IS 3 BP 8 EP 15 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 013PF UT WOS:000309316600002 PM 23091965 ER PT J AU Bamboat, ZM Kinnier, C Dursun, A Ferrone, CR Shellito, PC Berger, DL Bordeianou, L AF Bamboat, Zubin M. Kinnier, Christine Dursun, Abdulmetin Ferrone, Cristina R. Shellito, Paul C. Berger, David L. Bordeianou, Liliana TI Short-term Outcomes in Obese Patients after Colectomy for Adenocarcinoma at a Bariatric Center SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE Colon cancer; Obesity; Body mass index; Colectomy ID BODY-MASS INDEX; COLORECTAL-CANCER; SURGERY; CHEMOTHERAPY; PREDICTORS; IMPACT; RISK AB Obesity (body mass index a parts per thousand yen30) is associated with worse outcomes after colon cancer surgery. Most research, however, has been performed outside bariatric centers of excellence. We sought to determine the relationship between obesity and outcomes after colon cancer resection when performed at a center with bariatric expertise. We performed a retrospective review of 245 consecutive patients undergoing elective colectomy for adenocarcinoma at a single institution from 2008 to 2009. Body mass index, major and minor postoperative complications, tumor characteristics, lymph node yield, type of resection, and operating times were determined. Complication rates, operative times, and lymph node counts were all similar between the two weight groups. Obese patients had similar tumor characteristics at all stages when compared with nonobese patients. On multivariate analysis, obesity did not correlate with tumor size, tumor differentiation, or presence of lymphovascular or perineural invasion. We conclude that obese patients undergoing colon cancer resection at a bariatric center of excellence have similar tumor characteristics and equivalent short-term outcomes as do nonobese patients. C1 [Bamboat, Zubin M.; Kinnier, Christine; Dursun, Abdulmetin; Ferrone, Cristina R.; Shellito, Paul C.; Berger, David L.; Bordeianou, Liliana] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gastrointestinal Surg,Colon & Rectal Surg Pro, Boston, MA 02114 USA. RP Bordeianou, L (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gastrointestinal Surg,Colon & Rectal Surg Pro, 15 Parkman St,WAC 460, Boston, MA 02114 USA. EM lbordeianou@partners.org NR 28 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD OCT PY 2012 VL 16 IS 10 BP 1923 EP 1928 DI 10.1007/s11605-012-1978-3 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 008KF UT WOS:000308955100015 PM 22847573 ER PT J AU Conway, KL Goel, G Sokol, H Manocha, M Mizoguchi, E Terhorst, C Bhan, AK Gardet, A Xavier, RJ AF Conway, Kara L. Goel, Gautam Sokol, Harry Manocha, Monika Mizoguchi, Emiko Terhorst, Cox Bhan, Atul K. Gardet, Agnes Xavier, Ramnik J. TI p40(phox) Expression Regulates Neutrophil Recruitment and Function during the Resolution Phase of Intestinal Inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; EPITHELIAL WOUND REPAIR; POPULATION-BASED COHORT; CROHNS-DISEASE; BOWEL-DISEASE; GENE-EXPRESSION; CYSTIC-FIBROSIS; EXPERIMENTAL COLITIS; POLYMORPHONUCLEAR LEUKOCYTES; SUSCEPTIBILITY LOCI AB NADPH oxidase is a multisubunit complex that assembles during phagocytosis to generate reactive oxygen species. Several components of this complex have been implicated in chronic granulomatous disease and Crohn's disease, highlighting the importance of reactive oxygen species in regulating host immune response. In this study, we use genetically deficient mice to elucidate how p40(phox), one subunit of the NADPH oxidase complex, functions during intestinal inflammation. We show that p40(phox) deficiency enhances inflammation in both dextran sulfate sodium-induced and innate immune-mediated murine colitis models. This inflammation is characterized by severe colonic tissue injury, increased proinflammatory cytokines, and increased neutrophil recruitment. We demonstrate that neutrophils are essential during the recovery phase of intestinal inflammation and that p40(phox) expression is necessary for this restitution. Lastly, using an integrative bioinformatic approach, we show that p40(phox) deficiency leads to upregulation of chemokine receptor 1 and downregulation of enzymes involved in glycan modifications, including fucosyltransferases and sialyltransferases, during inflammation. We propose that p40(phox) deficiency enhances intestinal inflammation through the dysregulation of these two pathways in neutrophils. The Journal of Immunology, 2012, 189: 3631-3640. C1 [Conway, Kara L.; Goel, Gautam; Sokol, Harry; Gardet, Agnes; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol,Richard B Simches Re, Boston, MA 02114 USA. [Conway, Kara L.; Sokol, Harry; Manocha, Monika; Mizoguchi, Emiko; Terhorst, Cox; Bhan, Atul K.; Gardet, Agnes; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Conway, Kara L.; Sokol, Harry; Mizoguchi, Emiko; Gardet, Agnes; Xavier, Ramnik J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Sokol, Harry] St Antoine Hosp, Dept Gastroenterol, F-75571 Paris, France. [Sokol, Harry] Univ Paris 06, Publ Assistance Hosp Paris, F-75571 Paris, France. [Bhan, Atul K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Manocha, Monika; Terhorst, Cox] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Immunol, Boston, MA 02215 USA. [Conway, Kara L.; Goel, Gautam; Gardet, Agnes; Xavier, Ramnik J.] Broad Inst Massachusetts Inst Technol, Cambridge, MA 02142 USA. [Conway, Kara L.; Goel, Gautam; Gardet, Agnes; Xavier, Ramnik J.] Harvard Univ, Cambridge, MA 02142 USA. RP Xavier, RJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Computat & Integrat Biol,Richard B Simches Re, 185 Cambridge St, Boston, MA 02114 USA. EM xavier@molbio.mgh.harvard.edu OI sokol, harry/0000-0002-2914-1822 FU National Institutes of Health [DK060049, DK086502, DK043351, AI062773, DK52510]; Leona M. and Harry B. Helmsley Charitable Trust; French Society of Gastroenterology; Bettencourt Schueller Foundation; Philippe Foundation; Arthur Sachs Scholarship FX This work was supported by National Institutes of Health Grants DK060049, DK086502, DK043351, AI062773 (to R.J.X.), and DK52510 (to C. T.) and by the Leona M. and Harry B. Helmsley Charitable Trust (to R.J.X.). H. S. was supported by grants from the French Society of Gastroenterology, the Bettencourt Schueller Foundation, the Philippe Foundation, and the Arthur Sachs Scholarship. NR 60 TC 17 Z9 17 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2012 VL 189 IS 7 BP 3631 EP 3640 DI 10.4049/jimmunol.1103746 PG 10 WC Immunology SC Immunology GA 011KT UT WOS:000309164300040 PM 22914050 ER PT J AU Duhaime, AC AF Duhaime, Ann-Christine TI Traumatic brain injury in KIDs SO JOURNAL OF NEUROSURGERY-PEDIATRICS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Pediat Neurosurg, Boston, MA 02114 USA. RP Duhaime, AC (reprint author), Massachusetts Gen Hosp, Dept Pediat Neurosurg, Boston, MA 02114 USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1933-0707 J9 J NEUROSURG-PEDIATR JI J. Neurosurg.-Pediatr. PD OCT PY 2012 VL 10 IS 4 BP 255 EP 256 DI 10.3171/2012.4.PEDS12143 PG 2 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA 015YX UT WOS:000309485300001 PM 22900486 ER PT J AU Sherwood, M Hage, FG Heo, J Shaw, LJ Cerqueira, MD Iskandrian, AE AF Sherwood, Melody Hage, Fadi G. Heo, Jack Shaw, Leslee J. Cerqueira, Manuel D. Iskandrian, Ami E. TI SPECT myocardial perfusion imaging as an endpoint SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Editorial Material ID QUANTITATIVE-ANALYSIS; NUCLEAR CARDIOLOGY; QUANTIFICATION; IMAGES; TRIAL C1 [Sherwood, Melody; Heo, Jack; Iskandrian, Ami E.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Hage, Fadi G.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Shaw, Leslee J.] Emory Univ, Sch Med, Atlanta, GA USA. [Cerqueira, Manuel D.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP Iskandrian, AE (reprint author), Univ Alabama Birmingham, 318 LHRB, Birmingham, AL 35294 USA. EM aiskand@uab.edu OI Hage, Fadi/0000-0002-1397-4942 NR 15 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD OCT PY 2012 VL 19 IS 5 BP 891 EP 894 DI 10.1007/s12350-012-9583-0 PG 4 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 014AV UT WOS:000309348300005 PM 22669737 ER PT J AU Shaw, LJ Hage, FG Berman, DS Hachamovitch, R Iskandrian, A AF Shaw, Leslee J. Hage, Fadi G. Berman, Daniel S. Hachamovitch, Rory Iskandrian, Ami TI Prognosis in the era of comparative effectiveness research: Where is nuclear cardiology now and where should it be? SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article ID CORONARY-ARTERY-DISEASE; EMISSION COMPUTED-TOMOGRAPHY; MYOCARDIAL-PERFUSION SPECT; HEART-RATE RESPONSE; CARDIOVASCULAR-MAGNETIC-RESONANCE; LEFT-VENTRICULAR DYSFUNCTION; ACUTE CHEST-PAIN; RANDOMIZED CONTROLLED-TRIAL; ALL-CAUSE MORTALITY; OPTIMAL MEDICAL THERAPY C1 [Shaw, Leslee J.] Emory Univ, Sch Med, Emory Clin Cardiovasc Res Inst, Atlanta, GA 30324 USA. [Hage, Fadi G.; Iskandrian, Ami] Univ Alabama Birmingham, Birmingham, AL USA. [Hage, Fadi G.; Iskandrian, Ami] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Berman, Daniel S.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Hachamovitch, Rory] Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP Shaw, LJ (reprint author), Emory Univ, Sch Med, Emory Clin Cardiovasc Res Inst, 1462 Clifton Rd NE,Room529, Atlanta, GA 30324 USA. EM lshaw3@emory.edu NR 159 TC 61 Z9 61 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD OCT PY 2012 VL 19 IS 5 BP 1026 EP 1043 DI 10.1007/s12350-012-9593-y PG 18 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 014AV UT WOS:000309348300020 PM 22760523 ER PT J AU Shaw, LJ Hage, FG Berman, DS Hachamovitch, R Iskandrian, A AF Shaw, Leslee J. Hage, Fadi G. Berman, Daniel S. Hachamovitch, Rory Iskandrian, Ami TI Prognosis in the era of comparative effectiveness research: Where is nuclear cardiology now and where should it be? (vol 19, pg 1026, 2012) SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Correction ID CORONARY FLOW RESERVE C1 [Shaw, Leslee J.] Emory Univ, Sch Med, Emory Clin Cardiovasc Res Inst, Atlanta, GA 30324 USA. [Hage, Fadi G.; Iskandrian, Ami] Univ Alabama Birmingham, Birmingham, AL USA. [Hage, Fadi G.; Iskandrian, Ami] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Berman, Daniel S.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Hachamovitch, Rory] Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP Shaw, LJ (reprint author), Emory Univ, Sch Med, Emory Clin Cardiovasc Res Inst, 1462 Clifton Rd NE,Room 529, Atlanta, GA 30324 USA. EM lshaw3@emory.edu NR 3 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD OCT PY 2012 VL 19 IS 5 BP 1092 EP 1093 DI 10.1007/s12350-012-9605-y PG 2 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 014AV UT WOS:000309348300028 ER PT J AU McKinney, JS Masjuan, J Purroy, F Calvet, D Ay, H Cucchiara, BL AF McKinney, James S. Masjuan, Jaime Purroy, Francisco Calvet, David Ay, Hakan Cucchiara, Brett L. TI Safety of Thrombolytic Therapy for Acute Ischemic Stroke after Recent Transient Ischemic Attack SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES LA English DT Article DE Hemorrhage; stroke; thrombolysis; tissue plasminogen activator; transient ischemic attack ID TISSUE-PLASMINOGEN ACTIVATOR; PERIPHERAL-VASCULAR-DISEASE; CARDIOVASCULAR-RADIOLOGY; LESION VOLUME; RISK; PREDICTORS; TRIAL; TIA; INTERVENTION; VALIDATION AB Background: The objective of this study was to assess the rate of symptomatic intracerebral hemorrhage (SICH) in patients given thrombolytic therapy for acute ischemic stroke (AIS) after recent transient ischemic attack (TIA). Methods: This was a multicenter study of patients with confirmed TIA within 7 days before an AIS that was treated with intravenous (IV), intra-arterial (IA), or mechanical thrombolysis. A total of 23 cases were identified. Results: The median time interval between index TIA and AIS was 9 hours. The median National Institutes of Health Stroke Scale score at the time of AIS was 12. The median time interval between stroke onset and thrombolytic treatment was 90 minutes. Thrombolytic therapies included IV thrombolysis (70%), IA thrombolysis (17%), IA and mechanical thrombolysis (9%), and IV followed by IA and mechanical thrombolysis (4%). The rate of postthrombolysis SICH in this group was 8.6% (2/23). Conclusions: The rate of SICH in our cohort appears similar to overall postthrombolysis hemorrhage rates. C1 [McKinney, James S.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, New Brunswick, NJ 08901 USA. [Masjuan, Jaime] Hosp Univ Ramon y Cajal, Dept Neurol, Madrid, Spain. [Purroy, Francisco] Univ Lleida, Dept Neurol, Lleida, Spain. [Calvet, David] Ctr Hosp St Anne, Dept Neurol, Paris, France. [Ay, Hakan] Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. [Ay, Hakan] Massachusetts Gen Hosp, AA Martinos Ctr Imaging, Dept Neurol, Boston, MA 02114 USA. [Ay, Hakan] Massachusetts Gen Hosp, AA Martinos Ctr Imaging, Dept Radiol, Boston, MA 02114 USA. [Cucchiara, Brett L.] Hosp Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. RP McKinney, JS (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, 125 Paterson St,2nd Floor, New Brunswick, NJ 08901 USA. EM mckinnjs@umdnj.edu OI Purroy, Francisco/0000-0002-1808-5968 FU NINDS NIH HHS [R01 NS059710] NR 19 TC 4 Z9 4 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD OCT PY 2012 VL 21 IS 7 BP 551 EP 554 DI 10.1016/j.jstrokecerebrovasdis.2010.12.008 PG 4 WC Neurosciences; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 015FC UT WOS:000309429900007 PM 21295996 ER PT J AU Phitayakorn, R Mchenry, CR AF Phitayakorn, Roy Mchenry, Christopher R. TI Perioperative considerations in patients with adrenal tumors SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Review DE perioperative management; adrenal tumors; pheochromocytoma; adrenal carcinoma; aldosteronoma; Cushing's syndrome ID CUSHINGS-SYNDROME; PRIMARY ALDOSTERONISM; ADRENOCORTICAL CARCINOMA; LAPAROSCOPIC ADRENALECTOMY; PREOPERATIVE MANAGEMENT; TYROSINE-HYDROXYLASE; PROGNOSTIC-FACTORS; CLINICAL-FEATURES; ANGIOTENSIN-II; PHEOCHROMOCYTOMA AB In this article the pre-operative, intraoperative, and post-operative management of patients with pheochromocytoma, aldosterone-producing adenoma, cortisol-producing tumors, and adrenal cortical carcinoma are reviewed. A detailed plan for pre-operative assessment and medical optimization is discussed. The potential intraoperative and post-operative complications that occur in patients with an adrenal tumor are reviewed with emphasis on recognition, treatment and prevention. Recommendations for anesthetic management, intraoperative and post-operative monitoring, blood pressure management, laboratory analysis and medication adjustments are presented. J. Surg. Oncol. 2012; 106:604610. (C) 2012 Wiley Periodicals, Inc. C1 [Phitayakorn, Roy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Phitayakorn, Roy] Harvard Univ, Sch Med, Boston, MA USA. [Mchenry, Christopher R.] MetroHlth Med Ctr, Dept Surg, Cleveland, OH 44109 USA. [Mchenry, Christopher R.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. RP Mchenry, CR (reprint author), MetroHlth Med Ctr, Dept Surg, H 918,2500 MetroHlth Dr, Cleveland, OH 44109 USA. EM cmchenry@metrohealth.org OI Phitayakorn, Roy/0000-0002-8327-1484 NR 81 TC 1 Z9 1 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-4790 EI 1096-9098 J9 J SURG ONCOL JI J. Surg. Oncol. PD OCT PY 2012 VL 106 IS 5 SI SI BP 604 EP 610 DI 10.1002/jso.23129 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA 007FC UT WOS:000308873200013 PM 22513507 ER PT J AU Zimmerman, RM Kim, JM Jupiter, JB AF Zimmerman, Ryan M. Kim, Jaehon M. Jupiter, Jesse B. TI Arthritis of the Distal Radioulnar Joint: From Darrach to Total Joint Arthroplasty SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Review ID SAUVE-KAPANDJI PROCEDURE; TRIANGULAR FIBROCARTILAGE COMPLEX; ONE-BONE FOREARM; RHEUMATOID-ARTHRITIS; MALUNITED FRACTURES; RADIUS FRACTURES; ULNA; RECONSTRUCTION; INSTABILITY; DISORDERS AB The distal radioulnar joint (DRUJ) is a complex structure that contributes to full, painless forearm rotation and weight bearing. Stability requires adequate bony architecture and robust soft-tissue support. Arthritis of the DRUJ between the sigmoid notch of the distal radius and the ulnar head can be caused by traumatic, inflammatory, congenital, and degenerative processes. Initial management of symptomatic DRUJ arthritis is nonsurgical. Surgery is reserved for patients with refractory pain. Although outcomes typically are positive following excision of the distal ulna, serious potential postoperative complications include instability and potentially painful impingement of the residual distal ulnar stump. Procedures used to manage the unstable residual ulna include soft-tissue stabilization techniques and DRUJ implant arthroplasty. C1 [Zimmerman, Ryan M.; Kim, Jaehon M.; Jupiter, Jesse B.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Zimmerman, RM (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. NR 54 TC 10 Z9 10 U1 0 U2 2 PU AMER ACAD ORTHOPAEDIC SURGEONS PI ROSEMENT PA 6300 N RIVER ROAD, ROSEMENT, IL 60018-4262 USA SN 1067-151X J9 J AM ACAD ORTHOP SUR JI J. Am. Acad. Orthop. Surg. PD OCT PY 2012 VL 20 IS 10 BP 623 EP 632 DI 10.5435/JAAOS-20-10-623 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 016AK UT WOS:000309489400002 PM 23027692 ER PT J AU D'Adamo, D AF D'Adamo, David TI Is adjuvant chemotherapy useful for soft-tissue sarcomas? SO LANCET ONCOLOGY LA English DT Editorial Material ID GASTROINTESTINAL STROMAL TUMOR; TRIAL; METAANALYSIS; SURVIVAL; IMATINIB C1 Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02215 USA. RP D'Adamo, D (reprint author), Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Brookline Ave,Dana 1212, Boston, MA 02215 USA. EM david_dadamo@dfci.harvard.edu NR 12 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD OCT PY 2012 VL 13 IS 10 BP 968 EP 970 DI 10.1016/S1470-2045(12)70390-X PG 4 WC Oncology SC Oncology GA 016IG UT WOS:000309510600028 PM 22954505 ER PT J AU Camidge, DR Bang, YJ Kwak, EL Iafrate, AJ Varella-Garcia, M Fox, SB Riely, GJ Solomon, B Ou, SHI Kim, DW Salgia, R Fidias, P Engelman, JA Gandhi, L Janne, PA Costa, DB Shapiro, GI LoRusso, P Ruffner, K Stephenson, P Tang, YY Wilner, K Clark, JW Shaw, AT AF Camidge, D. Ross Bang, Yung-Jue Kwak, Eunice L. Iafrate, A. John Varella-Garcia, Marileila Fox, Stephen B. Riely, Gregory J. Solomon, Benjamin Ou, Sai-Hong I. Kim, Dong-Wan Salgia, Ravi Fidias, Panagiotis Engelman, Jeffrey A. Gandhi, Leena Jaenne, Pasi A. Costa, Daniel B. Shapiro, Geoffrey I. LoRusso, Patricia Ruffner, Katherine Stephenson, Patricia Tang, Yiyun Wilner, Keith Clark, Jeffrey W. Shaw, Alice T. TI Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study SO LANCET ONCOLOGY LA English DT Article ID EML4-ALK FUSION GENE; ANAPLASTIC LYMPHOMA; INHIBITOR CRIZOTINIB; ACQUIRED-RESISTANCE; CLINICAL-FEATURES; KINASE INHIBITORS; KRAS MUTATIONS; SOLID TUMORS; C-MET; EGFR AB Background ALK fusion genes occur in a subset of non-small-cell lung cancers (NSCLCs). We assessed the tolerability and activity of crizotinib in patients with NSCLC who were prospectively identified to have an ALK fusion within the first-in-man phase 1 crizotinib study. Methods In this phase 1 study, patients with ALK-positive stage III or IV NSCLC received oral crizotinib 250 mg twice daily in 28-day cycles. Endpoints included tumour responses, duration of response, time to tumour response, progression-free survival (PFS), overall survival at 6 and 12 months, and determination of the safety and tolerability and characterisation of the plasma pharmacokinetic profile of crizotinib after oral administration. Responses were analysed in evaluable patients and PFS and safety were analysed in all patients. This study is registered with ClinicalTrials.gov, number NCT00585195. Findings Between Aug 27, 2008, and June 1, 2011, 149 ALK-positive patients were enrolled, 143 of whom were included in the response-evaluable population. 87 of 143 patients had an objective response (60.8%, 95% CI 52.3-68.9), including three complete responses and 84 partial responses. Median time to first documented objective response was 7.9 weeks (range 2.1-39.6) and median duration of response was 49.1 weeks (95% CI 39.3-75.4). The response rate seemed to be largely independent of age, sex, performance status, or line of treatment. Median PFS was 9.7 months (95% CI 7.7-12.8). Median overall survival data are not yet mature, but estimated overall survival at 6 and 12 months was 87.9% (95% CI 81.3-92.3) and 74.8% (66.4-81.5), respectively. 39 patients continued to receive crizotinib for more than 2 weeks after progression because of perceived ongoing clinical benefit from the drug (12 for at least 6 months from the time of their initial investigator-defined disease progression). Overall, 144 (97%) of 149 patients experienced treatment-related adverse events, which were mostly grade 1 or 2. The most common adverse events were visual effects, nausea, diarrhoea, constipation, vomiting, and peripheral oedema. The most common treatment-related grade 3 or 4 adverse events were neutropenia (n=9), raised alanine aminotransferase (n=6), hypophosphataemia (n=6), and lymphopenia (n=6). Interpretation Crizotinib is well tolerated with rapid, durable responses in patients with ALK-positive NSCLC. There seems to be potential for ongoing benefit after initial disease progression in this population, but a more formal definition of ongoing benefit in this context is needed. C1 [Bang, Yung-Jue; Kim, Dong-Wan] Seoul Natl Univ, Coll Med, Seoul, South Korea. [Kwak, Eunice L.; Iafrate, A. John; Fidias, Panagiotis; Engelman, Jeffrey A.; Clark, Jeffrey W.; Shaw, Alice T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fox, Stephen B.; Solomon, Benjamin] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Riely, Gregory J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Ou, Sai-Hong I.] Univ Calif Irvine, Irvine, CA USA. [Salgia, Ravi] Univ Chicago, Chicago, IL 60637 USA. [Costa, Daniel B.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [LoRusso, Patricia] Karmanos Canc Inst, Detroit, MI USA. [Ruffner, Katherine; Tang, Yiyun; Wilner, Keith] Pfizer Oncol, La Jolla, CA USA. [Stephenson, Patricia] Rho, Chapel Hill, NC USA. [Gandhi, Leena; Jaenne, Pasi A.; Shapiro, Geoffrey I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Camidge, D. Ross; Varella-Garcia, Marileila] Univ Colorado Denver, Aurora, CO USA. RP Camidge, DR (reprint author), Univ Colorado, Div Med Oncol, Anschutz Med Campus,Mailstop F704,Room ACP 1058, Aurora, CO 80045 USA. EM ross.camidge@ucdenver.edu RI Kim, Dong-Wan/J-5391-2012; Bang, Yung Jue/J-2759-2012; OI Costa, Daniel/0000-0002-0689-395X; Gandhi, Leena/0000-0002-2398-9179; Fox, Stephen/0000-0002-7648-8896 FU Pfizer; Abbott Molecular; Chugai; Boehringer Ingelheim; Bristol-Myers Squibb; GlaxoSmithKline; Infinity Pharmaceuticals; Merck; Daiichi; Tragara; Novartis; Ariad; Genentech; AstraZeneca; Roche; National Cancer Institute [P50-CA090578]; American Society of Clinical Oncology Conquer Cancer Foundation; Massachusetts General Hospital Cancer Center and Pathology Department FX DRC, Y-JB, ELK, AJI, BS, S-HIO, D-WK, PAJ, DBC, PLR, and ATS received honoraria or consulting fees from Pfizer. ELK, GJR, BS, and JWC received research funding from Pfizer. AJI, MV-G, and GJR received honoraria or consulting fees from Abbott Molecular. GJR, LG, and ATS received honoraria or consulting fees from Chugai. GJR received research funding from Chugai, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Infinity Pharmaceuticals, and Merck; and honoraria or consulting fees from Daiichi and Tragara. GJR and ATS received honoraria or consulting fees from Novartis and Ariad and research funding from Novartis. PF received honoraria or consulting fees from Genentech. DBC received honoraria or consulting fees from AstraZeneca and Roche. KR, YT, and KW are employees and stockholders of Pfizer. ATS received research funding from AstraZeneca. SBF, RS, JAE, GIS, and PS declare that they have no conflicts of interest.; We thank all the participating patients, their families, and the network of investigators, research nurses, study coordinators, and operations staff. The phase 1 clinical trial was sponsored by Pfizer. Investigators were supported in part by the National Cancer Institute P50-CA090578 (PAJ, DBC), the American Society of Clinical Oncology Conquer Cancer Foundation (DBC), and by internal funds from the Massachusetts General Hospital Cancer Center and Pathology Department (ATS, AJI). Editorial assistance was provided by Martin Quinn at Acumed (Tytherington, UK) and was funded by Pfizer. NR 45 TC 502 Z9 544 U1 12 U2 63 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD OCT PY 2012 VL 13 IS 10 BP 1011 EP 1019 DI 10.1016/S1470-2045(12)70344-3 PG 9 WC Oncology SC Oncology GA 016IG UT WOS:000309510600038 PM 22954507 ER PT J AU Lips, ES Cornelisse, LN Toonen, RF Min, JL Hultman, CM Holmans, PA O'Donovan, MC Purcell, SM Smit, AB Verhage, M Sullivan, PF Visscher, PM Posthuma, D AF Lips, E. S. Cornelisse, L. N. Toonen, R. F. Min, J. L. Hultman, C. M. Holmans, P. A. O'Donovan, M. C. Purcell, S. M. Smit, A. B. Verhage, M. Sullivan, P. F. Visscher, P. M. Posthuma, D. CA Int Schizophrenia Consortium TI Functional gene group analysis identifies synaptic gene groups as risk factor for schizophrenia SO MOLECULAR PSYCHIATRY LA English DT Article DE GWAS; ISC; GAIN; gene group analysis; synapse; genome-wide association ID GENOME-WIDE ASSOCIATION; VARIANTS CONFERRING RISK; COMMON VARIANTS; PATHWAY ANALYSIS; LINKAGE; CONVERGENCE; ROBUSTNESS; ORGANELLE; PROTEINS; DISORDER AB Schizophrenia is a highly heritable disorder with a polygenic pattern of inheritance and a population prevalence of similar to 1%. Previous studies have implicated synaptic dysfunction in schizophrenia. We tested the accumulated association of genetic variants in expert-curated synaptic gene groups with schizophrenia in 4673 cases and 4965 healthy controls, using functional gene group analysis. Identifying groups of genes with similar cellular function rather than genes in isolation may have clinical implications for finding additional drug targets. We found that a group of 1026 synaptic genes was significantly associated with the risk of schizophrenia (P = 7.6 x 10(-11)) and more strongly associated than 100 randomly drawn, matched control groups of genetic variants (P < 0.01). Subsequent analysis of synaptic subgroups suggested that the strongest association signals are derived from three synaptic gene groups: intracellular signal transduction (P = 2.0 x 10(-4)), excitability (P = 9.0 x 10(-4)) and cell adhesion and trans-synaptic signaling (P = 2.4 x 10(-3)). These results are consistent with a role of synaptic dysfunction in schizophrenia and imply that impaired intracellular signal transduction in synapses, synaptic excitability and cell adhesion and trans-synaptic signaling play a role in the pathology of schizophrenia. Molecular Psychiatry (2012) 17, 996-1006; doi:10.1038/mp.2011.117; published online 20 September 2011 C1 [Lips, E. S.; Cornelisse, L. N.; Toonen, R. F.; Min, J. L.; Verhage, M.; Posthuma, D.] Vrije Univ Amsterdam, CNCR, Dept Funct Genom, NL-1081 HV Amsterdam, Netherlands. [Hultman, C. M.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Hultman, C. M.] Uppsala Univ, Dept Neurosci, Uppsala, Sweden. [Holmans, P. A.; O'Donovan, M. C.] Cardiff Univ, Sch Med, Dept Psychol Med, Cardiff, Wales. [Purcell, S. M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Purcell, S. M.] Harvard Univ, Sch Med, Boston, MA USA. [Purcell, S. M.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Purcell, S. M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Sullivan, P. F.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Visscher, P. M.] Queensland Inst Med Res, Queensland Stat Genet Lab, Brisbane, Qld 4006, Australia. [Posthuma, D.] Vrije Univ Amsterdam Med Ctr, Dept Med Genom, Amsterdam, Netherlands. RP Posthuma, D (reprint author), Vrije Univ Amsterdam, CNCR, Dept Funct Genom, De Boelelaan 1085, NL-1081 HV Amsterdam, Netherlands. EM danielle.posthuma@cncr.vu.nl RI Holmans, Peter/F-4518-2015; OI Holmans, Peter/0000-0003-0870-9412; O'Donovan, Michael/0000-0001-7073-2379; verhage, matthijs/0000-0002-6085-7503; Toonen, Ruud/0000-0002-9900-4233; Visscher, Peter/0000-0002-2143-8760 FU Netherlands Scientific Organization [NWO 480-05-003]; NWO/VIDI [452-05-318]; TOP ZonMW [40-00812-98-07-032]; NWO-ALW Pilot grant [051.07.004]; Eurospin consortium [FP7 HEALTH-F2-2009-241498]; Neuroscience Campus Amsterdam; European Union Seventh Framework Program [HEALTHF2-2009-242167]; Centre for Medical Systems Biology (CMSB); Australian National Health and Medical Research Council (NHMRC) [389892, 613672]; Royal Netherlands Academy of Arts and Sciences (KNAW) FX Statistical analyses were carried out on the Genetic Cluster Computer (http://www.geneticcluster.org), which is financially supported by the Netherlands Scientific Organization (NWO 480-05-003). The genotyping of the samples was provided through the Genetic Association Information Network (GAIN). The data set(s) used for the analyses described in this manuscript were obtained from the GAIN Database found at http://view.ncbi.nlm.nih.gov/dbgap, controlled through dbGaP accession number phs000021.v2.p1. Samples and associated phenotype data for the genome-wide association of schizophrenia study were provided by the Molecular Genetics of Schizophrenia Collaboration (PI: PV Gejman, Evanston Northwestern Healthcare (ENH) and Northwestern University, Evanston, IL, USA). We gratefully acknowledge financial support of the NWO/VIDI (452-05-318 to DP), TOP ZonMW (40-00812-98-07-032 to LNC and MV), NWO-ALW Pilot grant (051.07.004 to MV), FP7 HEALTH-F2-2009-241498 (Eurospin consortium), Neuroscience Campus Amsterdam and the European Union Seventh Framework Program under grant agreement no. HEALTHF2-2009-242167 ('SynSys' project). ABS and MV are supported by the Centre for Medical Systems Biology (CMSB). PMV acknowledges funding from the Australian National Health and Medical Research Council (NHMRC grants 389892 and 613672). Collaboration between DP and PMV was supported through a Visiting Professorship grant from the Royal Netherlands Academy of Arts and Sciences (KNAW). NR 35 TC 59 Z9 59 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD OCT PY 2012 VL 17 IS 10 BP 996 EP 1006 DI 10.1038/mp.2011.117 PG 11 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 012DB UT WOS:000309214500005 PM 21931320 ER PT J AU Schwartz, CE Kunwar, PS Greve, DN Kagan, J Snidman, NC Bloch, RB AF Schwartz, C. E. Kunwar, P. S. Greve, D. N. Kagan, J. Snidman, N. C. Bloch, R. B. TI A phenotype of early infancy predicts reactivity of the amygdala in male adults SO MOLECULAR PSYCHIATRY LA English DT Article DE amygdala; anxiety; infant; novelty; sex differences; temperament ID POSTTRAUMATIC-STRESS-DISORDER; FACIAL EMOTION DISCRIMINATION; GENERALIZED ANXIETY DISORDER; LONG-TERM POTENTIATION; SEX-DIFFERENCES; SOCIAL ANXIETY; BEHAVIORAL-INHIBITION; FEAR EXTINCTION; PANIC DISORDER; FUNCTIONAL MRI AB One of the central questions that has occupied those disciplines concerned with human development is the nature of continuities and discontinuities from birth to maturity. The amygdala has a central role in the processing of novelty and emotion in the brain. Although there is considerable variability among individuals in the reactivity of the amygdala to novel and emotional stimuli, the origin of these individual differences is not well understood. Four-month old infants called high reactive (HR) demonstrate a distinctive pattern of vigorous motor activity and crying to specific unfamiliar visual, auditory and olfactory stimuli in the laboratory. Low-reactive infants show the complementary pattern. Here, we demonstrate that the HR infant phenotype predicts greater amygdalar reactivity to novel faces almost two decades later in adults. A prediction of individual differences in brain function at maturity can be made on the basis of a single behavioral assessment made in the laboratory at 4 months of age. This is the earliest known human behavioral phenotype that predicts individual differences in patterns of neural activity at maturity. These temperamental differences rooted in infancy may be relevant to understanding individual differences in vulnerability and resilience to clinical psychiatric disorder. Males who were HR infants showed particularly high levels of reactivity to novel faces in the amygdala that distinguished them as adults from all other sex/temperament subgroups, suggesting that their amygdala is particularly prone to engagement by unfamiliar faces. These findings underline the importance of taking gender into account when studying the developmental neurobiology of human temperament and anxiety disorders. The genetic study of behavioral and biologic intermediate phenotypes (or 'endophenotypes') indexing anxiety-proneness offers an important alternative to examining phenotypes based on clinically defined disorder. As the HR phenotype is characterized by specific patterns of reactivity to elemental visual, olfactory and auditory stimuli, well before complex social behaviors such as shyness or fearful interaction with strangers can be observed, it may be closer to underlying neurobiological mechanisms than behavioral profiles observed later in life. This possibility, together with the fact that environmental factors have less time to impact the 4-month phenotype, suggests that this temperamental profile may be a fruitful target for high-risk genetic studies. Molecular Psychiatry (2012) 17, 1042-1050; doi:10.1038/mp.2011.96; published online 6 September 2011 C1 [Schwartz, C. E.] Massachusetts Gen Hosp, Psychiat Neurosci Program, Dept Psychiat, Dev Neuroimaging & Psychopathol Lab, Boston, MA 02114 USA. [Schwartz, C. E.; Kunwar, P. S.; Greve, D. N.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Schwartz, C. E.; Greve, D. N.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Greve, D. N.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Kagan, J.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Snidman, N. C.] Childrens Hosp, Child Dev Unit, Boston, MA 02115 USA. RP Schwartz, CE (reprint author), Massachusetts Gen Hosp, Psychiat Neurosci Program, Dept Psychiat, Dev Neuroimaging & Psychopathol Lab, Bldg 149-2627, Boston, MA 02114 USA. EM carl_schwartz@hms.harvard.edu FU National Institutes of Mental Health [R01MH071467, R01MH074848]; Center for Functional Neuroimaging Technologies [P41RR14075]; Biomedical Technology Program of the National Center for Research Resources (NCRR), National Institutes of Health FX We thank the families and children who have stayed with the study over 18 years. This study was supported by the National Institutes of Mental Health R01MH071467 and R01MH074848 (CES). This research was carried out in part at the Athinoula A Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41RR14075, a P41 Regional Resource supported by the Biomedical Technology Program of the National Center for Research Resources (NCRR), National Institutes of Health. NR 90 TC 26 Z9 26 U1 6 U2 22 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD OCT PY 2012 VL 17 IS 10 BP 1042 EP 1050 DI 10.1038/mp.2011.96 PG 9 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 012DB UT WOS:000309214500010 PM 21894151 ER PT J AU Simon, J AF Simon, Jack TI Very early MS - insights from MRI SO MULTIPLE SCLEROSIS JOURNAL LA English DT Review DE Clinically isolated syndrome; multiple sclerosis; magnetic resonance imaging; atrophy; gray matter ID CLINICALLY ISOLATED SYNDROMES; GRAY-MATTER ATROPHY; RADIOLOGICALLY ISOLATED SYNDROME; EARLY MULTIPLE-SCLEROSIS; GREY-MATTER; DIAGNOSTIC-CRITERIA; WHITE-MATTER; FOLLOW-UP; LESIONS; CONVERSION AB Magnetic resonance imaging (MRI) is likely to play an increasing role in efforts to understand the earliest changes in multiple sclerosis (MS) and narrowing the gap to new insights provided by the recent pathology literature showing early meningeal and cortical inflammatory disease and cortical gray matter demyelination. Much of the insight into early MS already comes from MRI as it evaluates patients at the time of a clinically isolated syndrome (CIS). Series show transition of tissue from normal to abnormal, and now often reveal gray matter more so than white matter pathology, deep gray more than cortical gray, and quantitative MRI changes preceding atrophy in early MS. But the CIS population is heterogeneous, likely including patients with many years' duration, as well as relatively recent onset disease. Efforts to evaluate earlier disease, possibly sub-populations of CIS, patients at risk for MS with strict criteria for a radiologically isolated syndrome, and tumefactive MS, combined with advanced MRI technology, may bring us closer to in vivo insight into truly early or earliest MS. C1 Portland VA Med Ctr, Portland, OR 97239 USA. RP Simon, J (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM jack.simon3@va.gov NR 29 TC 6 Z9 6 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD OCT PY 2012 VL 18 IS 10 BP 1372 EP 1376 DI 10.1177/1352458512452925 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 014EW UT WOS:000309359000002 PM 22760097 ER PT J AU Bove, RM Healy, B Augustine, A Musallam, A Gholipour, T Chitnis, T AF Bove, Riley M. Healy, Brian Augustine, Ann Musallam, Alexander Gholipour, Taha Chitnis, Tanuja TI Effect of gender on late-onset multiple sclerosis SO MULTIPLE SCLEROSIS JOURNAL LA English DT Article DE multiple sclerosis; geriatrics; progression; disability; female; menopause ID CLINICAL CHARACTERISTICS; SEX-RATIO; AGE; DISABILITY; BRAIN; RISK; ENHANCEMENT; POPULATION; IMPAIRMENT; PREDICTORS AB Objectives: We aimed to examine the incidence and disease course of late-onset multiple sclerosis (LOMS) compared with adult-onset MS (AOMS) in our clinic cohort, stratified based on gender and race, since both have been reported as important modifiers of disease outcomes in MS. Methods: Patients with LOMS and AOMS were compared in terms of demographic characteristics and disease course characteristics. Combined effects were investigated with a logistic regression model. Time from disease onset to sustained Expanded Disability Status Scale (EDSS) score of 6 was investigated using an extension of log-rank test appropriate for interval-censored data. Results: Some 7.96% of 4273 patients studied had an onset of MS after the age of 50 years (LOMS), and 1.33% experienced an onset after age 60. Progressive onset was more common in LOMS relative to AOMS. The proportion of women with progressive-onset disease was similar in AOMS and LOMS. Time to EDSS 6 was delayed in AOMS females compared with males; however, it was similar between males and females in the LOMS group. Conclusions: Women with LOMS have a different trajectory in terms of disease progression than women with AOMS. The effect of menopause combined with race/ethnicity on the MS disease course requires further investigation. C1 [Bove, Riley M.; Healy, Brian; Augustine, Ann; Musallam, Alexander; Gholipour, Taha; Chitnis, Tanuja] Brigham & Womens Hosp, Partners Multiple Sclerosis Ctr, Brookline, MA 02445 USA. [Healy, Brian] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. RP Chitnis, T (reprint author), Brigham & Womens Hosp, Partners Multiple Sclerosis Ctr, 1 Brookline Pl,Suite 602, Brookline, MA 02445 USA. EM tchitnis@partners.org FU National Multiple Sclerosis Society [RG 4256A 4/2] FX This work was supported by the National Multiple Sclerosis Society (RG 4256A 4/2 to T. Chitnis). NR 51 TC 23 Z9 23 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1352-4585 J9 MULT SCLER J JI Mult. Scler. J. PD OCT PY 2012 VL 18 IS 10 BP 1472 EP 1479 DI 10.1177/1352458512438236 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 014EW UT WOS:000309359000017 PM 22383227 ER PT J AU Kwong, LN Costello, JC Liu, HY Jiang, S Helms, TL Langsdorf, AE Jakubosky, D Genovese, G Muller, FL Jeong, JH Bender, RP Chu, GC Flaherty, KT Wargo, JA Collins, JJ Chin, LD AF Kwong, Lawrence N. Costello, James C. Liu, Huiyun Jiang, Shan Helms, Timothy L. Langsdorf, Aliete E. Jakubosky, David Genovese, Giannicola Muller, Florian L. Jeong, Joseph H. Bender, Ryan P. Chu, Gerald C. Flaherty, Keith T. Wargo, Jennifer A. Collins, James J. Chin, Lynda TI Oncogenic NRAS signaling differentially regulates survival and proliferation in melanoma SO NATURE MEDICINE LA English DT Article ID KINASE KINASE-1/2 INHIBITOR; EXPRESSION PROFILES; TUMOR PROGRESSION; BRAF INHIBITORS; MEK INHIBITION; PHASE-I; K-RAS; PATHWAY; CANCER; NETWORKS AB The discovery of potent inhibitors of the BRAF proto-oncogene has revolutionized therapy for melanoma harboring mutations in BRAF, yet NRAS-mutant melanoma remains without an effective therapy. Because direct pharmacological inhibition of the RAS proto-oncogene has thus far been unsuccessful, we explored systems biology approaches to identify synergistic drug combination(s) that can mimic RAS inhibition. Here, leveraging an inducible mouse model of NRAS-mutant melanoma, we show that pharmacological inhibition of mitogen-activated protein kinase kinase (MEK) activates apoptosis but not cell-cycle arrest, which is in contrast to complete genetic neuroblastoma RAS homolog (NRAS) extinction, which triggers both of these effects. Network modeling pinpointed cyclin-dependent kinase 4 (CDK4) as a key driver of this differential phenotype. Accordingly, combined pharmacological inhibition of MEK and CDK4 in vivo led to substantial synergy in therapeutic efficacy. We suggest a gradient model of oncogenic NRAS signaling in which the output is gated, resulting in the decoupling of discrete downstream biological phenotypes as a result of incomplete inhibition. Such a gated signaling model offers a new framework to identify nonobvious coextinction target(s) for combined pharmacological inhibition in NRAS-mutant melanomas. C1 [Kwong, Lawrence N.; Liu, Huiyun; Jiang, Shan; Langsdorf, Aliete E.; Jakubosky, David; Genovese, Giannicola; Muller, Florian L.; Jeong, Joseph H.; Bender, Ryan P.; Chu, Gerald C.; Chin, Lynda] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kwong, Lawrence N.; Jiang, Shan; Helms, Timothy L.; Genovese, Giannicola; Muller, Florian L.; Chin, Lynda] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA. [Costello, James C.; Collins, James J.] Howard Hughes Med Inst, Dept Biomed Engn, Boston, MA 02115 USA. [Costello, James C.; Collins, James J.] Boston Univ, Ctr BioDynam, Boston, MA 02215 USA. [Chu, Gerald C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Flaherty, Keith T.] Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. [Wargo, Jennifer A.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. [Collins, James J.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Chin, Lynda] Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Houston, TX 77030 USA. RP Chin, LD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM lchin@mdanderson.org FU American Cancer Society [117842-PF-09-261-01-TBG]; US National Institutes of Health Director's Pioneer Award Program; Howard Hughes Medical Institute; US National Institutes of Health [U01 CA141508]; Abby S. and Howard P. Milstein Innovation Award for Melanoma and Skin Cancer Research FX We thank G. Mills, Y. Lu and N. Shih at the MD Anderson Reverse Phase Protein Array core facility; E. Fox at the Dana-Farber Cancer Institute Microarray core facility; S. Zhou for mouse husbandry; R. DePinho and G. Draetta and members of the laboratory, including S. Quayle, M. Chen, A. Blanchette and J. Kamara, for insightful discussions; R. Kwong for manuscript proofreading; D. Camacho for helping develop the TRAP algorithm; and M. Bar-Eli (University of Texas MD Anderson Cancer Center, Houston, Texas) for the SB-2 cell line. L. N. K. is supported by the Postdoctoral Fellowship (117842-PF-09-261-01-TBG) from the American Cancer Society. J. J. C. is supported by the US National Institutes of Health Director's Pioneer Award Program and the Howard Hughes Medical Institute. This work was supported by funding from the US National Institutes of Health to L. C. (U01 CA141508). L. C. is a recipient of the Abby S. and Howard P. Milstein 2009 Innovation Award for Melanoma and Skin Cancer Research and a CPRIT (Cancer Prevention Research Institute of Texas) Scholar in Cancer Research. NR 45 TC 113 Z9 113 U1 1 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 2012 VL 18 IS 10 BP 1503 EP U96 DI 10.1038/nm.2941 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 017JZ UT WOS:000309587500028 PM 22983396 ER PT J AU Huang, H Kong, D Byun, KH Ye, CP Koda, S Lee, DH Oh, BC Lee, SW Lee, B Zabolotny, JM Kim, MS Bjorbaek, C Lowell, BB Kim, YB AF Huang, Hu Kong, Dong Byun, Kyung Hee Ye, Chianping Koda, Shuichi Lee, Dae Ho Oh, Byung-Chul Lee, Sam W. Lee, Bonghee Zabolotny, Janice M. Kim, Min Seon Bjorbaek, Christian Lowell, Bradford B. Kim, Young-Bum TI Rho-kinase regulates energy balance by targeting hypothalamic leptin receptor signaling SO NATURE NEUROSCIENCE LA English DT Article ID PROOPIOMELANOCORTIN MESSENGER-RNA; BODY-WEIGHT; POMC NEURONS; FOOD-INTAKE; ARCUATE NUCLEUS; GLUCOSE-HOMEOSTASIS; IN-VIVO; INSULIN; MICE; ROCK1 AB Leptin regulates energy balance. However, knowledge of the critical intracellular transducers of leptin signaling remains incomplete. We found that Rho-kinase 1 (ROCK1) regulates leptin action on body weight homeostasis by activating JAK2, an initial trigger of leptin receptor signaling. Leptin promoted the physical interaction of JAK2 and ROCK1, thereby increasing phosphorylation of JAK2 and downstream activation of Stat3 and FOXO1. Mice lacking ROCK1 in either pro-opiomelanocortin (POMC) or agouti-related protein neurons, mediators of leptin action, displayed obesity and impaired leptin sensitivity. In addition, deletion of ROCK1 in the arcuate nucleus markedly enhanced food intake, resulting in severe obesity. Notably, ROCK1 was a specific mediator of leptin, but not insulin, regulation of POMC neuronal activity. Our data identify ROCK1 as a key regulator of leptin action on energy homeostasis. C1 [Huang, Hu; Kong, Dong; Ye, Chianping; Koda, Shuichi; Lee, Dae Ho; Zabolotny, Janice M.; Bjorbaek, Christian; Lowell, Bradford B.; Kim, Young-Bum] Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. [Huang, Hu; Kong, Dong; Ye, Chianping; Koda, Shuichi; Lee, Dae Ho; Zabolotny, Janice M.; Bjorbaek, Christian; Lowell, Bradford B.; Kim, Young-Bum] Harvard Univ, Sch Med, Boston, MA USA. [Byun, Kyung Hee; Oh, Byung-Chul; Lee, Bonghee; Kim, Young-Bum] Gachon Univ Med & Sci, Grad Sch Med, Lee Gil Ya Canc & Diabet Inst, Inchon, South Korea. [Lee, Sam W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Lee, Sam W.] Harvard Univ, Sch Med, Charlestown, MA USA. [Kim, Min Seon] Univ Ulsan, Coll Med, Asan Inst Life Sci, Dept Internal Med, Seoul, South Korea. RP Kim, YB (reprint author), Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. EM ykim2@bidmc.harvard.edu FU US National Institutes of Health [1R01DK083567, 5R01CA127247, P30DK05752]; American Diabetes Association [1-09-RA-87] FX We would like to thank B. Kahn and T. Flier for valuable suggestions; L. Huo, S.D. Ha, S. Bayer, S. Yee, T. Liu, S.-M. Hong, N. Wang, D. Kim, B. Enkhjargal for technical assistance, and L. Wei for DN-Rockl cDNA. This work was supported by grants from the US National Institutes of Health (1R01DK083567 to Y.-B.K., 5R01CA127247 to S.W.L. and P30DK05752 Ito D.K.) and the American Diabetes Association (1-09-RA-87 to Y.-B.K.). NR 34 TC 30 Z9 31 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD OCT PY 2012 VL 15 IS 10 BP 1391 EP 1398 DI 10.1038/nn.3207 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 013VZ UT WOS:000309335300019 PM 22941110 ER PT J AU Rudinskiy, N Hawkes, JM Betensky, RA Eguchi, M Yamaguchi, S Spires-Jones, TL Hyman, BT AF Rudinskiy, Nikita Hawkes, Jonathan M. Betensky, Rebecca A. Eguchi, Megumi Yamaguchi, Shun Spires-Jones, Tara L. Hyman, Bradley T. TI Orchestrated experience-driven Arc responses are disrupted in a mouse model of Alzheimer's disease SO NATURE NEUROSCIENCE LA English DT Article ID PROTEIN TRANSGENIC MICE; LONG-TERM POTENTIATION; AMYLOID-BETA; SYNAPTIC PLASTICITY; IN-VIVO; VISUAL-CORTEX; CORTICAL-NEURONS; COGNITIVE FUNCTION; GENE-EXPRESSION; SENILE PLAQUES AB Experience-induced expression of immediate-early gene Arc (also known as Arg3.1) is known to be important for consolidation of memory. Using in vivo longitudinal multiphoton imaging, we found orchestrated activity-dependent expression of Arc in the mouse extrastriate visual cortex in response to a structured visual stimulation. In wild-type mice, the amplitude of the Arc response in individual neurons strongly predicted the probability of reactivation by a subsequent presentation of the same stimulus. In a mouse model of Alzheimer's disease, this association was markedly disrupted in the cortex, specifically near senile plaques. Neurons in the vicinity of plaques were less likely to respond, but, paradoxically, there were stronger responses in those few neurons around plaques that did respond. To the extent that the orchestrated pattern of Arc expression reflects nervous system responses to and physiological consolidation of behavioral experience, the disruption in Arc patterns reveals plaque-associated interference with neural network integration. C1 [Rudinskiy, Nikita; Hawkes, Jonathan M.; Spires-Jones, Tara L.; Hyman, Bradley T.] Harvard Univ, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Alzheimers Dis Res Lab,Dept Neurol,Sch Med, Charlestown, MA USA. [Hawkes, Jonathan M.] Northeastern Univ, Behav Neurosci Program, Boston, MA 02115 USA. [Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Eguchi, Megumi; Yamaguchi, Shun] Gifu Univ, Grad Sch Med, Div Morphol Neurosci, Gifu, Japan. RP Hyman, BT (reprint author), Harvard Univ, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Alzheimers Dis Res Lab,Dept Neurol,Sch Med, Charlestown, MA USA. EM bhyman@partners.org OI Spires-Jones, Tara/0000-0003-2530-0598 FU Swiss National Science Foundation; Swiss Foundation for Grants in Biology and Medicine; Gilbert fund; US National Institutes of Health [AG033670, AG08487]; Harvard NeuroDiscovery Center FX We thank A. Muzikansky (Harvard), B. Urbanc and B. Cohen (Drexel) for their help with statistical analysis. We also thank all the members of the Hyman laboratory for their input, discussions and help with the equipment. N.R. is supported by the fellowships from the Swiss National Science Foundation and the Swiss Foundation for Grants in Biology and Medicine. This research is supported by a gift from the Gilbert fund, grants from the US National Institutes of Health (AG033670 to T.L.S.-J. and AG08487 to B.T.H.) and a grant from the Harvard NeuroDiscovery Center to R.A.B. NR 50 TC 31 Z9 31 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD OCT PY 2012 VL 15 IS 10 BP 1422 EP 1429 DI 10.1038/nn.3199 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 013VZ UT WOS:000309335300023 PM 22922786 ER PT J AU Yiu, G Young, LH AF Yiu, Glenn Young, Lucy H. TI Progressive Outer Retinal Necrosis Presenting as Cherry Red Spot SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Letter DE Progressive outer retinal necrosis; PORN; Cherry red spot; Herpes zoster ID OPTIC NEURITIS; AIDS; PATIENT AB Purpose: To report a case of progressive outer retinal necrosis (PORN) presenting as a cherry red spot. Methods: Case report. Results: A 53-year-old woman with recently diagnosed HIV and varicella-zoster virus (VZV) aseptic meningitis developed rapid sequential vision loss in both eyes over 2 months. Her exam showed a "cherry red spot" in both maculae with peripheral atrophy and pigmentary changes, consistent with PORN. Due to her late presentation and the rapid progression of her condition, she quickly developed end-stage vision loss in both eyes. Conclusions: PORN should be considered within the differential diagnosis of a "cherry red spot." Immune-deficient patients with a history of herpetic infection who present with visual loss warrant prompt ophthalmological evaluation. C1 [Yiu, Glenn; Young, Lucy H.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, Boston, MA 02114 USA. RP Yiu, G (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, Boston, MA 02114 USA. EM glenn_yiu@meei.harvard.edu NR 6 TC 0 Z9 0 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD OCT PY 2012 VL 20 IS 5 BP 384 EP 386 DI 10.3109/09273948.2012.710705 PG 3 WC Ophthalmology SC Ophthalmology GA 015UM UT WOS:000309471900014 PM 22957726 ER PT J AU Metsis, V Huang, H Andronesi, OC Makedon, F Tzika, A AF Metsis, Vangelis Huang, Heng Andronesi, Ovidiu C. Makedon, Fillia Tzika, Aria TI Heterogeneous data fusion for brain tumor classification SO ONCOLOGY REPORTS LA English DT Article DE data fusion; gene selection; bioinformatics; magnetic resonance spectroscopy ID MAGNETIC-RESONANCE SPECTROSCOPY; GENE-EXPRESSION; PHOSPHOLIPID-METABOLISM; GLIOBLASTOMA-MULTIFORME; MALIGNANT GLIOMAS; FEATURE-SELECTION; SURVIVAL AB Current research in biomedical informatics involves analysis of multiple heterogeneous data sets. This includes patient demographics, clinical and pathology data, treatment history, patient outcomes as well as gene expression, DNA sequences and other information sources such as gene ontology. Analysis of these data sets could lead to better disease diagnosis, prognosis, treatment and drug discovery. In this report, we present a novel machine learning framework for brain tumor classification based on heterogeneous data fusion of metabolic and molecular datasets, including state-of-the-art high-resolution magic angle spinning (HRMAS) proton (H-1) magnetic resonance spectroscopy and gene transcriptome profiling, obtained from intact brain tumor biopsies. Our experimental results show that our novel framework outperforms any analysis using individual dataset. C1 [Metsis, Vangelis] Univ Texas Arlington, Dept Comp Sci & Engn, Heracleia Human Ctr Comp Lab, Arlington, TX 76019 USA. [Andronesi, Ovidiu C.; Tzika, Aria] Massachusetts Gen Hosp, Dept Surg, NMR Surg Lab, Boston, MA 02114 USA. [Andronesi, Ovidiu C.; Tzika, Aria] Harvard Univ, Sch Med, Shriners Burn Inst, Boston, MA 02114 USA. [Andronesi, Ovidiu C.; Tzika, Aria] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Metsis, V (reprint author), Univ Texas Arlington, Dept Comp Sci & Engn, Heracleia Human Ctr Comp Lab, 500 UTA Blvd, Arlington, TX 76019 USA. EM vmetsis@uta.edu NR 23 TC 2 Z9 2 U1 2 U2 9 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD OCT PY 2012 VL 28 IS 4 BP 1413 EP 1416 DI 10.3892/or.2012.1931 PG 4 WC Oncology SC Oncology GA 013OT UT WOS:000309315400041 PM 22842996 ER PT J AU Duigenan, S Anupindi, SA Nimkin, K AF Duigenan, Shauna Anupindi, Sudha A. Nimkin, Katherine TI Imaging of multifocal hepatic lesions in pediatric patients SO PEDIATRIC RADIOLOGY LA English DT Review DE Pediatric; Multifocal; Liver ID RADIOLOGIC-PATHOLOGICAL CORRELATION; FOCAL NODULAR HYPERPLASIA; CAT-SCRATCH DISEASE; BUDD-CHIARI-SYNDROME; OF-THE-LITERATURE; UNDIFFERENTIATED EMBRYONAL SARCOMA; HEPATOCELLULAR-CARCINOMA; PELIOSIS HEPATIS; MR FINDINGS; HEPATOBILIARY TUBERCULOSIS AB Imaging plays a vital role in detection and characterization of multifocal liver lesions in children. Numerous causes for these lesions exist, including benign and malignant neoplasms, infectious lesions, and congenital and inflammatory conditions. The imaging spectrum of multifocal liver lesions in children is presented with emphasis on key imaging features, differential diagnoses and helpful relevant clinical features. C1 [Duigenan, Shauna; Nimkin, Katherine] Massachusetts Gen Hosp, Div Pediat Radiol, Boston, MA 02114 USA. [Anupindi, Sudha A.] Childrens Hosp Philadelphia, Dept Radiol, Philadelphia, PA 19104 USA. RP Duigenan, S (reprint author), Ottawa Gen Hosp, Dept Med Imaging, 501 Smyth Rd,Gen Campus, Ottawa, ON K1H 8L6, Canada. EM sduigenan@toh.on.ca NR 91 TC 1 Z9 1 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD OCT PY 2012 VL 42 IS 10 BP 1155 EP 1168 DI 10.1007/s00247-012-2400-8 PG 14 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA 014BW UT WOS:000309351100001 PM 22565297 ER PT J AU Duval, S Massaro, JM Jaff, MR Boden, WE Alberts, MJ Califf, RM Eagle, KA D'Agostino, RB Pedley, A Fonarow, GC Murabito, JM Steg, PG Bhatt, DL Hirsch, AT AF Duval, Sue Massaro, Joseph M. Jaff, Michael R. Boden, William E. Alberts, Mark J. Califf, Robert M. Eagle, Kim A. D'Agostino, Ralph B., Sr. Pedley, Alison Fonarow, Gregg C. Murabito, Joanne M. Steg, P. Gabriel Bhatt, Deepak L. Hirsch, Alan T. CA REACH Registry Investigators TI An evidence-based score to detect prevalent peripheral artery disease (PAD) SO VASCULAR MEDICINE LA English DT Review DE ankle-brachial index; peripheral artery disease; prevalence; registry; risk score ID RISK SCORE; CARDIOVASCULAR-DISEASE; MANAGEMENT; PATHOPHYSIOLOGY; INDIVIDUALS; PROBABILITY; VALIDATION; PREDICTION; DERIVATION; PROFILE AB Detection of peripheral artery disease (PAD) typically entails collection of medical history, physical examination, and noninvasive imaging, but whether a risk factor-based model has clinical utility in population screening is unclear. Our objective was to derive and validate a new score for estimating PAD probability in individuals or populations. PAD presence was determined by a history of previous or current intermittent claudication associated with an ankle-brachial index (ABI) of < 0.9 or previous lower extremity arterial intervention. Multivariable stepwise logistic regression identified cross-sectional correlates of PAD from demographic, clinical, and laboratory variables. Analyses were derived from 18,049 US REACH (REduction of Atherothrombosis for Continued Health) Registry outpatients with a complete baseline risk factor profile (enrolled from December 2003 to June 2004). Model performance was assessed internally using 10-fold cross validation, and effect estimates were used to generate the score. The model was externally validated using the Framingham Offspring Study. Age, sex, smoking, diabetes mellitus, body mass index, hypertension stage, and history of heart failure, coronary artery disease, and cerebrovascular disease were predictive of PAD prevalence. The model had reasonable discrimination on derivation and internal validation (c-statistic = 0.61 and 0.60, respectively) and external validation (c-statistic = 0.63 [ABI < 0.9] or 0.64 [clinical PAD]). The model-estimated PAD prevalence varied more than threefold from lowest to highest decile (range, 4.5-16.7) and corresponded closely with actual PAD prevalence in each population. In conclusion, this new tool uses clinical variables to estimate PAD prevalence. While predictive power may be limited, it may improve PAD detection in vulnerable, at-risk populations. C1 [Duval, Sue] Univ Minnesota, Sch Med, Lillehei Clin Res Unit, Div Cardiovasc, Minneapolis, MN 55455 USA. [Massaro, Joseph M.; D'Agostino, Ralph B., Sr.; Pedley, Alison] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Massaro, Joseph M.; D'Agostino, Ralph B., Sr.; Pedley, Alison] Harvard Clin Res Inst, Boston, MA USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Boden, William E.] Samuel S Stratton VA Med Ctr, Albany, NY USA. [Boden, William E.] Albany Med Ctr, Dept Med, Albany, NY USA. [Alberts, Mark J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Califf, Robert M.] Duke Univ, Med Ctr, Durham, NC USA. [Califf, Robert M.] Duke Translat Med Inst, Durham, NC USA. [Eagle, Kim A.] Univ Michigan, Ctr Cardiovasc, Ann Arbor, MI 48109 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Steg, P. Gabriel] Univ Paris 07, INSERM, U698, Paris, France. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Hirsch, Alan T.] Univ Minnesota, Sch Publ Hlth, Div Cardiovasc, Minneapolis, MN 55455 USA. RP Duval, S (reprint author), Univ Minnesota, Sch Med, Lillehei Clin Res Unit, Div Cardiovasc, 420 Delaware St SE,MMC 508, Minneapolis, MN 55455 USA. EM duval002@umn.edu OI Murabito, Joanne/0000-0002-0192-7516; Massaro, Joseph/0000-0002-2682-4812 FU Bristol-Myers Squibb; sanofi-aventis; Waksman Foundation (Tokyo, Japan); Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership; Abbott Laboratories; Biosite; Cardiac Sciences; Blue Cross Blue Shield of Michigan; Hewlett Foundation; Mardigian Fund; Pfizer; Varbedian Fund; Servier; AstraZeneca; Eisai; Amarin; Ethicon; Medtronic; Medicines Company; National Heart, Lung, and Blood Institute; Cytokinetics; Abbott Vascular FX The REACH Registry is endorsed by the World Heart Federation. Financial support is provided by Bristol-Myers Squibb, sanofi-aventis, and the Waksman Foundation (Tokyo, Japan). Editorial support was funded by the Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership. The statistical support provided by Drs D'Agostino Sr, Massaro, and Pedley was also funded by this partnership.; SD had a consultancy relationship with Abbott Vascular and Summit Doppler. JM (Dr Massaro) and AP had support from sanofi-aventis for the submitted work. MJ had a consultancy relationship with Abbott Vascular, Arsenal Medical, AtheroMed, Baxter Healthcare, Boston Scientific, Cordis Endovascular, LC Sciences, Medtronic, Micell Technologies, Nexeon MedSystems, and Takeda Pharmaceuticals. MJ has held stock/stock options in Access Closure, Hotspur Technologies, ICON Interventional, Setagon, Inc., Square One, TMI Group, and Vascular Therapies LLC. MJ has been a board member of VIVA Physicians. WB had a consultancy relationship with Gilead Scientific. WB has received grants/grants pending from Abbott Laboratories. WB has received payment for lectures including service on speakers' bureaus from Abbott Laboratories, Gilead Scientific, and sanofi-aventis. WB has received payment for development of educational presentations from Gilead Scientific and sanofi-aventis. WB has had travel/accommodations/meeting expenses unrelated to activities listed with Abbott Laboratories, Gilead Scientific, and sanofi-aventis. RC had support from sanofi-aventis for the submitted work. RC had a consultancy relationship and travel/accommodations/meeting expenses unrelated to activities listed with sanofi-aventis. KE has received grant/research support from Biosite, Bristol-Myers Squibb, Cardiac Sciences, Blue Cross Blue Shield of Michigan, Hewlett Foundation, Mardigian Fund, Pfizer, sanofi-aventis, and the Varbedian Fund. KE had a consultancy relationship with the National Institutes of Health, the National Heart, Lung, and Blood Institute, Pfizer, sanofi-aventis, and the Robert Wood Johnson Foundation. GF had a consultancy relationship with and received payment for lectures including service on speaker's bureaus with Bristol-Myers Squibb and sanofi-aventis. PGS had support from sanofi-aventis for the submitted work. PGS had a consultancy relationship with Astellas Pharma, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Inc./Eli Lilly alliance, GlaxoSmithKline, Medtronic, Merck, Otsuka Pharmaceutical, Roche, sanofi-aventis, Servier, and The Medicines Company. PGS has received grants/grants pending from Servier. PGS has received payment for development of educational presentations including service on speakers' bureaus from AstraZeneca, Boehringer Ingelheim, Merck, Pfizer, Roche, and Servier. PGS has held stock/stock options with Aterovax. DB had support from sanofi-aventis for the submitted work. DB has received grants/grants pending from AstraZeneca, Bristol-Myers Squibb, Eisai, sanofi-aventis, Amarin, Ethicon, Medtronic, and The Medicines Company. AH had support from Bristol-Myers Squibb and sanofi-aventis for the submitted work. AH had a consultancy relationship with Summit Doppler, ev3, and Talecris. AH has received grants from the National Heart, Lung, and Blood Institute, Cytokinetics, and Abbott Vascular. NR 23 TC 7 Z9 7 U1 0 U2 7 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1358-863X J9 VASC MED JI Vasc. Med. PD OCT PY 2012 VL 17 IS 5 BP 342 EP 351 DI 10.1177/1358863X12445102 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 014EV UT WOS:000309358900008 PM 22711750 ER PT J AU Gupta, S Vij, A Cafiero, E Bloom, D Agarwal, S Donelan, K Kopans, D Saini, S AF Gupta, Supriya Vij, Abhinav Cafiero, Elizabeth Bloom, David Agarwal, Sheela Donelan, Karen Kopans, Daniel Saini, Sanjay TI Retail Venue Based Screening Mammography: Assessment of Women's Preferences SO ACADEMIC RADIOLOGY LA English DT Article DE Screening mammography; retail venue mammography; women preferences ID BREAST-CARCINOMA MORTALITY; UNITED-STATES; IMPACT AB Rationale and Objectives: The aim of this study was to explore women's interest and preferences in undergoing screening mammography in a retail health care setting. Materials and Methods: Self-administered surveys were distributed to 400 mammography patients in May to June 2009. All of the women who were asked were eligible for screening (age >40 years, no abnormal mammographic findings in the recent past). Three hundred eighty-six screening-eligible women filled out and returned the self-administered survey. Results: The average respondent age was 57 years. Three hundred ten of the patients (80.3%) had college or postgraduate educations. Two hundred three (52.6%) reported annual incomes >$60,000. Two hundred forty-one respondents (62.4%) had been undergoing screening mammography for >10 years, while this was the first examination for eight patients (2%). More than half of the patients (n = 21 5 (55.7%]) affirmed their interest in undergoing annual screening mammography in a private area within a retail shopping facility. Most preferred a pharmacy (77%) over Wal-Mart or a grocery store. Appealing factors about a retail setting were proximity to home (90%), free parking (62%), and operating hours (48.8%). Conclusions: There is interest among women in undergoing screening mammography at retail health care clinics, preferably pharmacies. The provision of services at a convenient location can increase adherence to guidelines for screening mammography. C1 [Gupta, Supriya; Vij, Abhinav; Agarwal, Sheela; Kopans, Daniel; Saini, Sanjay] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. [Cafiero, Elizabeth; Bloom, David] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Donelan, Karen] Mongan Inst Hlth Policy, Boston, MA USA. RP Gupta, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, White 270,55 Fruit St, Boston, MA 02114 USA. EM riya10.in@gmail.com NR 16 TC 2 Z9 4 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD OCT PY 2012 VL 19 IS 10 BP 1268 EP 1272 DI 10.1016/j.acra.2012.04.022 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 011VF UT WOS:000309193700014 PM 22958721 ER PT J AU Jang, YC Liu, YH Hayworth, CR Bhattacharya, A Lustgarten, MS Muller, FL Chaudhuri, A Qi, WB Li, Y Huang, JY Verdin, E Richardson, A Van Remmen, H AF Jang, Young C. Liu, Yuhong Hayworth, Christopher R. Bhattacharya, Arunabh Lustgarten, Michael S. Muller, Florian L. Chaudhuri, Asish Qi, Wenbo Li, Yan Huang, Jing-Yi Verdin, Eric Richardson, Arlan Van Remmen, Holly TI Dietary restriction attenuates age-associated muscle atrophy by lowering oxidative stress in mice even in complete absence of CuZnSOD SO AGING CELL LA English DT Article DE Aging; calorie restriction; mice; mitochondria; oxidative stress; reactive oxygen species; sarcopenia; skeletal muscle ID RAT SKELETAL-MUSCLE; CALORIC RESTRICTION; NEUROMUSCULAR-JUNCTION; MITOCHONDRIAL-FUNCTION; SUPEROXIDE-DISMUTASE; MOTOR-NEURONS; PROTON LEAK; SARCOPENIA; DEGENERATION; ACETYLATION AB Age-related loss of muscle mass and function, sarcopenia, has a major impact on the quality of life in the elderly. Among the proposed causes of sarcopenia are mitochondrial dysfunction and accumulated oxidative damage during aging. Dietary restriction (DR), a robust dietary intervention that extends lifespan and modulates age-related pathology in a variety of species, has been shown to protect from sarcopenia in rodents. Although the mechanism(s) by which DR modulates aging are still not defined, one potential mechanism is through modulation of oxidative stress and mitochondrial dysfunction. To directly test the protective effect of DR against oxidative stressinduced muscle atrophy in vivo, we subjected mice lacking a key antioxidant enzyme, CuZnSOD (Sod1) to DR (60% of ad libitum fed diet). We have previously shown that the Sod1-/- mice exhibit an acceleration of sarcopenia associated with high oxidative stress, mitochondrial dysfunction, and severe neuromuscular innervation defects. Despite the dramatic atrophy phenotype in the Sod1-/- mice, DR led to a reversal or attenuation of reduced muscle function, loss of innervation, and muscle atrophy in these mice. DR improves mitochondrial function as evidenced by enhanced Ca2+ regulation and reduction of mitochondrial reactive oxygen species (ROS). Furthermore, we show upregulation of SIRT3 and MnSOD in DR animals, consistent with reduced mitochondrial oxidative stress and reduced oxidative damage in muscle tissue measured as F2-isoprostanes. Collectively, our results demonstrate that DR is a powerful mediator of mitochondrial function, mitochondrial ROS production, and oxidative damage, providing a solid protection against oxidative stressinduced neuromuscular defects and muscle atrophy in vivo even under conditions of high oxidative stress. C1 [Jang, Young C.; Liu, Yuhong; Bhattacharya, Arunabh; Muller, Florian L.; Qi, Wenbo; Li, Yan; Richardson, Arlan; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Jang, Young C.; Liu, Yuhong; Bhattacharya, Arunabh; Lustgarten, Michael S.; Muller, Florian L.; Chaudhuri, Asish; Qi, Wenbo; Li, Yan; Richardson, Arlan; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Hayworth, Christopher R.] Univ Texas Austin, Neurobiol Sect, Austin, TX 78712 USA. [Hayworth, Christopher R.] Univ Texas Austin, Inst Neurosci, Austin, TX 78712 USA. [Lustgarten, Michael S.] Univ Texas Hlth Sci Ctr San Antonio, Dept Physiol, San Antonio, TX 78229 USA. [Chaudhuri, Asish] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. [Chaudhuri, Asish; Qi, Wenbo; Li, Yan; Richardson, Arlan; Van Remmen, Holly] S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX 78229 USA. [Huang, Jing-Yi; Verdin, Eric] Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94158 USA. RP Van Remmen, H (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, 15355 Lambda Dr, San Antonio, TX 78245 USA. EM vanremmen@uthscsa.edu OI Verdin, Eric/0000-0003-3703-3183 FU UTHSCSA; NIH-NCI [P30 CA54174]; NIH-NIA [P01AG19316]; American Federation for Aging Research; [P01AG020591] FX We would like to thank Dr. Ting Ting Huang for providing Sod1 null breeders, Dr. Noah Weisleder and Dr. Pei Lin for their help with in vivo electroporation, and Marian Sabia, Amanda Jernigan, Barbara Hunter, Vivian Diaz, Jimmy Wewer, and Dr. Victoria Frohlich for their technical support. Some of the images were generated in the Core Optical Imaging Facility and EM Facility, which are supported by UTHSCSA, NIH-NCI P30 CA54174 (CTRC at UTHSCSA), and NIH-NIA P01AG19316. Also supported by P01AG020591 (HVR, AR) and a Julie Martin Mid-Career grant from the American Federation for Aging Research (HVR). NR 41 TC 27 Z9 27 U1 0 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1474-9718 J9 AGING CELL JI Aging Cell PD OCT PY 2012 VL 11 IS 5 BP 770 EP 782 DI 10.1111/j.1474-9726.2012.00843.x PG 13 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 007EK UT WOS:000308871400006 PM 22672615 ER PT J AU Maguilnik, I Neumann, WL Sonnenberg, A Genta, RM AF Maguilnik, I. Neumann, W. L. Sonnenberg, A. Genta, R. M. TI Reactive gastropathy is associated with inflammatory conditions throughout the gastrointestinal tract SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; COLLAGENOUS COLITIS; BILE REFLUX; LYMPHOCYTIC COLITIS; GASTRIC-MUCOSA; DIFFERENTIAL-DIAGNOSIS; CLINICAL-SIGNIFICANCE; OPERATED STOMACH; PEPTIC-ULCER; FEATURES AB Background The epidemiology of reactive gastropathy and its relationship with other conditions of the gastrointestinal tract associated with NSAID use have not been evaluated. Aims To test the hypothesis that if reactive gastropathy shares common aetiological factors with these conditions, the analysis of a large cohort would unveil associations. Methods We queried a national pathology database for subjects with a diagnosis of reactive gastropathy; controls were patients with normal gastric biopsies. We also extracted diagnoses of H. pylori infection, intestinal metaplasia, duodenal lymphocytosis, duodenitis, ileitis, microscopic colitis and focal colitis. Results Of 504 011 patients with gastric biopsies, 69 101 had oesophageal, 166 134 duodenal, 13 010 ileal and 83 334 colonic biopsies. Reactive gastropathy was diagnosed in 15.6% of patients, H. pylori infection in 10.3% and normal gastric mucosa in 16.3%. Reactive gastropathy was evenly distributed across the US and increased from 2.0% in the first decade of life to >20% in octogenarians. Compared with controls, reactive gastropathy was significantly associated with Barrett's mucosa (OR 1.21 95% CI 1.16129); duodenitis (OR 1.36; 95% CI 1.281.44); duodenal intraepithelial lymphocytosis (OR 1.25; 95% CI 1.131.39); active ileitis (OR 1.88; 95% CI 1.472.40); focal active colitis (OR 1.57; 95% CI 1.331.86); and collagenous colitis (OR 1.50; 95% CI 1.122.03). Conclusions Reactive gastropathy, a common histopathological feature of the stomach, shows an age-dependent rise and is associated with changes of the digestive tract believed to be caused by NSAID use or duodenogastric reflux. However, a large fraction of reactive gastropathy remains unexplained; its frequent occurrence merits further efforts at elucidating its aetiology. C1 [Maguilnik, I.] Univ Fed Rio Grande do Sul, Porto Alegre, RS, Brazil. [Neumann, W. L.; Genta, R. M.] Miraca Life Sci, Miraca Res Inst, Irving, TX 75039 USA. [Neumann, W. L.; Genta, R. M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Sonnenberg, A.] Portland VA Med Ctr, Portland, OR USA. [Genta, R. M.] Dallas VA Med Ctr, Dallas, TX USA. RP Genta, RM (reprint author), Miraca Life Sci, Miraca Res Inst, 6655 N MacArthur Blvd, Irving, TX 75039 USA. EM robert.genta@utsouthwestern.edu FU Miraca Life Sciences, Irving TX FX Dr Neumann's gastrointestinal pathology fellowship was partially funded by Miraca Life Sciences, Irving TX. Dr Genta is an employee of Miraca Life Sciences, Irving TX. NR 38 TC 7 Z9 7 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD OCT PY 2012 VL 36 IS 8 BP 736 EP 743 DI 10.1111/apt.12031 PG 8 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 007KT UT WOS:000308887900005 PM 22928604 ER PT J AU Zhang, XH Lee, JE Ma, J Je, YJ Wu, KN Willett, WC Fuchs, CS Giovannucci, EL AF Zhang, Xuehong Lee, Jung Eun Ma, Jing Je, Youjin Wu, Kana Willett, Walter C. Fuchs, Charles S. Giovannucci, Edward L. TI Prospective cohort studies of vitamin B-6 intake and colorectal cancer incidence: modification by time? SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; COLON-CANCER; FOLIC-ACID; RISK; PLASMA; FOLATE; HEALTH; REPRODUCIBILITY; VALIDITY; WOMEN AB Background: The relation between vitamin B-6 intake and colorectal cancer risk remains uncertain. Objective: We prospectively evaluated whether a higher vitamin B-6 intake in the remote past is more strongly associated with a lower risk of colorectal cancer than is an intake in the recent past in the Nurses' Health Study and the Health Professionals Follow-Up Study. Design: We assessed vitamin B-6 intake every 4 y by using validated food-frequency questionnaires and followed 86,440 women and 44,410 men for <= 28 y. Cox proportional hazards regression was used to estimate multivariable RRs and 95% CIs. Results: The total vitamin B-6 intake was significantly associated with an similar to 20-30% lower risk of colorectal cancer in age-adjusted results, but this association became attenuated and nonsignificant after additional adjustment for nondietary and dietary factors. When the highest to lowest quintiles of cumulative total vitamin B-6 intake were compared, RRs (95% CIs) for colorectal cancer were 0.99 (0.80, 1.24; P-trend = 0.55) for women and 0.95 (0.73, 1.23; P-trend = 0.75) for men. For the same comparison, RRs were 0.92 (0.73, 1.16) for total vitamin B-6 intake 0-4 y before diagnosis, 0.99 (0.78, 1.26) for intake 4-8 y before diagnosis, 0.92 (0.71, 1.21) for intake 8-12 y before diagnosis, and 0.93 (0.69, 1.26) for intake 12-16 y before diagnosis in women. Corresponding RRs for men were 0.86 (0.63, 1.17), 0.96 (0.70, 1.32), 0.90 (0.63, 1.29), and 1.16 (0.75, 1.79). Results did not differ by cancer subsite, source of vitamin B-6 (food or supplement), alcohol consumption, or folate intake. Conclusion: Our data do not support a strong role of adulthood vitamin B-6 intake in colorectal carcinogenesis in these US health professionals. Am J Clin Nutr 2012;96:874-81. C1 [Zhang, Xuehong; Ma, Jing; Willett, Walter C.; Fuchs, Charles S.; Giovannucci, Edward L.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Zhang, Xuehong; Ma, Jing; Willett, Walter C.; Fuchs, Charles S.; Giovannucci, Edward L.] Harvard Univ, Sch Med, Boston, MA USA. [Lee, Jung Eun] Sookmyung Womens Univ, Dept Food & Nutr, Seoul, South Korea. [Je, Youjin; Wu, Kana; Willett, Walter C.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Willett, Walter C.; Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Zhang, XH (reprint author), Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. EM xuehong.zhang@channing.harvard.edu OI Lee, Jung Eun/0000-0003-1141-878X FU American Institute of Cancer Research; NIH [CA87969, CA55075] FX Supported by a grant from the American Institute of Cancer Research and by NIH grants CA87969 and CA55075. NR 28 TC 10 Z9 10 U1 0 U2 3 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 2012 VL 96 IS 4 BP 874 EP 881 DI 10.3945/ajcn.112.037267 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 008SN UT WOS:000308977000022 PM 22875713 ER PT J AU de Jesus-Gonzalez, N Robinson, E Penchev, R von Mehren, M Heinrich, MC Tap, W Wang, Q Demetri, G George, S Humphreys, BD AF de Jesus-Gonzalez, Nilka Robinson, Emily Penchev, Radostin von Mehren, Margaret Heinrich, Michael C. Tap, William Wang, Qian Demetri, George George, Suzanne Humphreys, Benjamin D. TI Regorafenib Induces Rapid and Reversible Changes in Plasma Nitric Oxide and Endothelin-1 SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE antiangiogenic therapy; blood pressure; endothelin-1; hypertension; nitric oxide ID RENAL-CELL CARCINOMA; INHIBITOR SUNITINIB; COLORECTAL-CANCER; BLOOD-PRESSURE; HYPERTENSION; BEVACIZUMAB; BIOMARKER; PATHWAY; ANGIOGENESIS; METAANALYSIS AB BACKGROUND Hypertension is a toxicity of antiangiogenic therapies and a possible biomarker that identifies patients with superior cancer outcomes. Understanding its mechanism will aid in treatment and could lead to the development of other biomarkers for predicting toxicity and anticancer efficacy. Recent evidence implicates nitric oxide (NO) suppression and endothelin-1 (ET-1) stimulation as potential mechanisms leading to antiangiogenic therapy-induced hypertension. The aim of this study was to evaluate the effects of regorafenib, a novel broad-spectrum kinase inhibitor with activity against multiple targets, including vascular endothelial growth factor receptor 2 inhibition, on NO and ET-1 levels. METHODS Regorafenib was administered to 32 subjects with gastrointestinal stromal tumor on a 3-week-on, 1-week-off basis. Plasma levels of NO and ET-1 were measured at baseline, 2, 4, and 6 weeks of therapy. Data analysis was by Wilcoxon rank-sum and paired t-tests. RESULTS Twenty subjects (63%) developed regorafenib-induced hypertension. Two weeks after starting regorafenib therapy, plasma ET-1 levels increased (25% increase, P < 0.05) and NO was suppressed (20% decrease, P < 0.05). These normalized after 1-week washout but ET-1 rose again by 30% (P < 0.05) and NO fell by 50% (P < 0.05) after restarting regorafenib. CONCLUSIONS These findings indicate that regorafenib induces a coordinated and reversible suppression of NO and stimulation of ET-1. Whether NO and ET-1 might predict therapeutic efficacy in these patients requires further study. C1 [Robinson, Emily; Penchev, Radostin; Humphreys, Benjamin D.] Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. [de Jesus-Gonzalez, Nilka] Boston Childrens Hosp, Dept Med, Div Nephrol, Boston, MA USA. [von Mehren, Margaret] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA. [Heinrich, Michael C.] Oregon Hlth & Sci Univ, Knight Canc Inst, Div Hematol Oncol, Portland, OR 97201 USA. [Tap, William] Mem Sloan Kettering Canc Ctr, Div Solid Tumors, Melanoma Sarcoma Serv, New York, NY 10021 USA. [Wang, Qian; Demetri, George; George, Suzanne] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Humphreys, Benjamin D.] Dana Farber Canc Inst, Lance Armstrong Fdn Adult Survivorship Clin, Boston, MA 02115 USA. RP Humphreys, BD (reprint author), Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA. EM bhumphreys@partners.org FU National Institutes of Health [T32-DK007726-27S1, DK088923]; Department of Veterans Affairs; Bayer; Novartis; AROG Pharmaceuticals; Bayer (Clinical Trials); MolecularMD; Pfizer; Glaxo-Smith-Kline; Johnson and Johnson; Bristol-Myers Squibb; Infinity Pharmaceuticals FX This work was supported by the National Institutes of Health Training Grant T32-DK007726-27S1 (to N.D.G) and DK088923 (to B.D.H.) and by a Merit Review from the Department of Veterans Affairs (to M.C.H.), and Bayer (to S.G.).; Nilka de Jesus-Gonzalez, none. Emily Robinson, none. Radostin Penchev, none. Michael Heinrich, research funding: Novartis, AROG Pharmaceuticals, Bayer (Clinical Trials), equity interest, MolecularMD. Margaret von Mehren, none. William Tap, none. Qian Wang, none. George Demetri, research funding, Novartis, Pfizer, Glaxo-Smith-Kline, Bayer, Johnson and Johnson, Bristol-Myers Squibb, Infinity Pharmaceuticals, consultant, Novartis, Pfizer, Glaxo-Smith-Kline, Bayer, Johnson and Johnson, Infinity Pharmaceuticals, honoraria, Novartis, Pfizer. Suzanne George, none. Benjamin D. Humphreys, none. NR 33 TC 9 Z9 10 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD OCT PY 2012 VL 25 IS 10 BP 1118 EP 1123 DI 10.1038/ajh.2012.97 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 006UU UT WOS:000308845500013 PM 22785409 ER PT J AU Felsenfeld, AJ Levine, BS AF Felsenfeld, Arnold J. Levine, Barton S. TI Approach to Treatment of Hypophosphatemia SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Hypophosphatemia; adenosine triphosphate (ATP); 2,3-diphosphoglycerate (2,3-DPG); fibroblast growth factor 23 (FGF-23) ID INTENSIVE-CARE-UNIT; INTRAVENOUS PHOSPHORUS THERAPY; KIDNEY-TRANSPLANT RECIPIENTS; ACUTE RESPIRATORY-FAILURE; ADENOSINE-TRIPHOSPHATE; MYOCARDIAL PERFORMANCE; SERUM PHOSPHORUS; PHOSPHATE; REPLACEMENT; 2,3-DIPHOSPHOGLYCERATE AB Hypophosphatemia can be acute or chronic. Acute hypophosphatemia with phosphate depletion is common in the hospital setting and results in significant morbidity and mortality. Chronic hypophosphatemia, often associated with genetic or acquired renal phosphate-wasting disorders, usually produces abnormal growth and rickets in children and osteomalacia in adults. Acute hypophosphatemia may be mild (phosphorus level, 2-2.5 mg/dL), moderate (1-1.9 mg/dL), or severe (<1 mg/dL) and commonly occurs in clinical settings such as refeeding, alcoholism, diabetic ketoacidosis, malnutrition/starvation, and after surgery (particularly after partial hepatectomy) and in the intensive care unit. Phosphate replacement can be given either orally, intravenously, intradialytically, or in total parenteral nutrition solutions. The rate and amount of replacement are empirically determined, and several algorithms are available. Treatment is tailored to symptoms, severity, anticipated duration of illness, and presence of comorbid conditions, such as kidney failure, volume overload, hypo-or hypercalcemia, hypo- or hyperkalemia, and acid-base status. Mild/moderate acute hypophosphatemia usually can be corrected with increased dietary phosphate or oral supplementation, but intravenous replacement generally is needed when significant comorbid conditions or severe hypophosphatemia with phosphate depletion exist. In chronic hypophosphatemia, standard treatment includes oral phosphate supplementation and active vitamin D. Future treatment for specific disorders associated with chronic hypophosphatemia may include cinacalcet, calcitonin, or dypyrimadole. Am J Kidney Dis. 60(4):655-661. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. C1 VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Levine, BS (reprint author), Nephrol Sect 111L, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM blevine@ucla.edu NR 43 TC 11 Z9 12 U1 0 U2 32 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD OCT PY 2012 VL 60 IS 4 BP 655 EP 661 DI 10.1053/j.ajkd.2012.03.024 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 010QO UT WOS:000309109400024 PM 22863286 ER PT J AU Bekris, LM Millard, S Lutz, F Li, G Galasko, DR Farlow, MR Quinn, JF Kaye, JA Leverenz, JB Tsuang, DW Yu, CE Peskind, ER AF Bekris, Lynn M. Millard, Steve Lutz, Franziska Li, Gail Galasko, Doug R. Farlow, Martin R. Quinn, Joseph F. Kaye, Jeffrey A. Leverenz, James B. Tsuang, Debby W. Yu, Chang-En Peskind, Elaine R. TI Tau phosphorylation pathway genes and cerebrospinal fluid tau levels in Alzheimer's disease SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE FYN; PPP2R4; MAPT; AD; CSF ID PROTEIN-TYROSINE KINASE; FYN KINASE; COGNITIVE IMPAIRMENTS; POLYMORPHISMS; ASSOCIATION; DIAGNOSIS; PATHOLOGY; BIOMARKER; PP2A AB Alzheimer's disease (AD) is characterized by the presence in the brain of amyloid plaques, consisting predominately of the amyloid beta peptide (A beta), and neurofibrillary tangles, consisting primarily of tau. Hyper-phosphorylated-tau (p-tau) contributes to neuronal damage, and both p-tau and total-tau (t-tau) levels are elevated in AD cerebrospinal fluid (CSF) compared to cognitively normal controls. Our hypothesis was that increased ratios of CSF phosphorylated-tau levels relative to total-tau levels correlate with regulatory region genetic variation of kinase or phosphatase genes biologically associated with the phosphorylation status of tau. Eighteen SNPs located within 5' and 3' regions of 5 kinase and 4 phosphatase genes, as well as two SNPs within regulatory regions of the MAPT gene were chosen for this analysis. The study sample consisted of 101 AD patients and 169 cognitively normal controls. Rs7768046 in the FYN kinase gene and rs913275 in the PPP2R4 phosphatase gene were both associated with CSF p-tau and t-tau levels in AD. These SNPs were also differentially associated with either CSF t-tau (rs7768046) or CSF p-tau (rs913275) relative to t-tau levels in AD compared to controls. These results suggest that rs7768046 and rs913275 both influence CSF tau levels in an AD-associated manner. (c) 2012 Wiley Periodicals, Inc. C1 [Bekris, Lynn M.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98108 USA. [Bekris, Lynn M.; Lutz, Franziska; Yu, Chang-En] VA Puget Sound Hlth Care Syst, GRECC, Seattle, WA USA. [Millard, Steve; Leverenz, James B.; Tsuang, Debby W.; Peskind, Elaine R.] VA Puget Sound Hlth Care Syst, NW Network VISN Mental Illness Res Educ & Clin Ct, Seattle, WA USA. [Leverenz, James B.] Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98108 USA. [Galasko, Doug R.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Galasko, Doug R.] VA Med Ctr San Diego, San Diego, CA USA. [Farlow, Martin R.] Indiana Univ Sch Med, Dept Neurol, Indianapolis, IN USA. [Quinn, Joseph F.; Kaye, Jeffrey A.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Quinn, Joseph F.; Kaye, Jeffrey A.] Portland VA Med Ctr, Portland, OR USA. [Leverenz, James B.] Parkinsons Dis Res Educ & Clin Ctr PADRECC, NW Network VISN 20, Roseburg, OR USA. RP Bekris, LM (reprint author), Univ Washington, Dept Med, Div Gerontol & Geriatr Med, VAPSHCS GRECC S182B,1660 S Columbian Way, Seattle, WA 98108 USA. EM lbekris@u.washington.edu RI Tsuang, Debby/L-7234-2016; OI Tsuang, Debby/0000-0002-4716-1894; Kaye, Jeffrey/0000-0002-9971-3478 FU U.S. Department of Veterans Affairs, Office of Research and Development Clinical Research and Development Program; Biomedical Laboratory Research Program; NIH [2P50AG005136-27, 1P50NS062684-01A1, K99AG034214-02]; University of Washington Alzheimer's Disease Research Center NIH [P50-AB005136]; University of California San Diego Alzheimer's Disease Research Center [AGO 5131] FX Grant sponsor: U.S. Department of Veterans Affairs, Office of Research and Development Clinical Research and Development Program; Grant sponsor: Biomedical Laboratory Research Program; Grant sponsor: NIH; Grant numbers: 2P50AG005136-27, 1P50NS062684-01A1, K99AG034214-02; Grant sponsor: University of Washington Alzheimer's Disease Research Center NIH; Grant number: P50-AB005136; Grant sponsor: University of California San Diego Alzheimer's Disease Research Center; Grant number: AGO 5131. NR 40 TC 8 Z9 8 U1 1 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT PY 2012 VL 159B IS 7 BP 874 EP 883 DI 10.1002/ajmg.b.32094 PG 10 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 007HR UT WOS:000308879900015 PM 22927204 ER PT J AU Yeung, A Lepoutre, V Wayne, P Yeh, G Slipp, LE Fava, M Denninger, JW Benson, H Fricchione, GL AF Yeung, Albert Lepoutre, Veronique Wayne, Peter Yeh, Gloria Slipp, Lauren E. Fava, Maurizio Denninger, John W. Benson, Herbert Fricchione, Gregory L. TI Tai Chi Treatment for Depression in Chinese Americans A Pilot Study SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Depression; Chinese; Tai Chi; Mind-Body Intervention; Randomized Clinical Trial ID RANDOMIZED CONTROLLED-TRIAL; PERCEIVED SOCIAL SUPPORT; PSYCHOMETRIC CHARACTERISTICS; MULTIDIMENSIONAL SCALE; RATING-SCALE; PRIMARY-CARE; EXERCISE; OUTCOMES; STRESS; DESIGN AB Yeung A, Lepoutre V, Wayne P, Yeh G, Slipp LE, Fava M, Denninger JW, Benson H: Tai chi treatment for depression in Chinese Americans: a pilot study. Am J Phys Med Rehabil 2012; 91: 863-870. Objective: This study examined the feasibility, safety, and efficacy of using tai chi for treating major depressive disorder. Design: Thirty-nine Chinese Americans with major depressive disorder were randomized into a 12-wk tai chi intervention or a waitlisted control group in a 2: 1 ratio. The key outcome measurement was the 17-item Hamilton Rating Scale for Depression. Positive response was defined as a decrease of 50% or more on the 17-item Hamilton Rating Scale for Depression, and remission was defined as a score of 7 or lower on the 17-item Hamilton Rating Scale for Depression. Results: Of the participants (n = 39), 77% were women, and mean (SD) age was 55 (10) years. There were 26 (67%) participants in the tai chi intervention group and 13 (33%) in the control group. Of the participants in the tai chi group, 73% completed the intervention; no adverse events were reported. We observed trends toward improvement in the tai chi intervention group, compared with the control group, in positive treatment-response rate (24% vs. 0%) and remission rate (19% vs. 0%), although the differences in our small sample did not reach statistical significance. Conclusions: A randomized controlled trial of tai chi is feasible and safe in Chinese American patients with major depressive disorder. These promising pilot study results inform the design of a more definitive trial. C1 [Yeung, Albert; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Yeung, Albert; Lepoutre, Veronique; Slipp, Lauren E.; Denninger, John W.; Benson, Herbert; Fricchione, Gregory L.] Massachusetts Gen Hosp, Benson Henry Inst, Boston, MA 02114 USA. [Yeung, Albert; Fava, Maurizio; Denninger, John W.; Fricchione, Gregory L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Wayne, Peter] Harvard Univ, Sch Med, Osher Ctr Integrat Med, Boston, MA USA. [Wayne, Peter] Brigham & Womens Hosp, Boston, MA 02115 USA. [Yeh, Gloria] Beth Israel Deaconess Med Ctr, Dept Med, Div Gen Med & Primary Care, Boston, MA 02215 USA. RP Yeung, A (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 1 Bowdoin Sq,6-F, Boston, MA 02114 USA. FU CDC [5R01DP000339] FX Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article. Supported by CDC grant 5R01DP000339. An abstract presenting these findings has been accepted for presentation at the American Psychiatric Association's 2012 Annual Meeting. NR 34 TC 17 Z9 17 U1 4 U2 30 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD OCT PY 2012 VL 91 IS 10 BP 863 EP 870 DI 10.1097/PHM.0b013e31825f1a67 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 012FU UT WOS:000309222100006 PM 22790795 ER PT J AU Filippi, CG Carlson, M Johnson, JM Burbank, HN Alsofrom, GF Andrews, T AF Filippi, Christopher G. Carlson, Morgan Johnson, Jason M. Burbank, Heather N. Alsofrom, Gary F. Andrews, Trevor TI Improvements in Lumbar Spine MRI at 3 T Using Parallel Transmission SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE 3-T MRI; lumbar spine MRI; parallel transmission MRI ID FIELD INHOMOGENEITY; B-1 INHOMOGENEITY; RF TRANSMISSION; NOISE; COILS; ACQUISITION; IMAGES AB OBJECTIVE. Parallel transmission MRI at 3 T improves image quality by reducing dielectric effects with radiofrequency shimming. The purpose of this study was to determine whether parallel transmission MRI improves signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in lumbar spine MRI at 3 T. MATERIALS AND METHODS. Ten healthy volunteers underwent T1-weighted MRI and nine healthy volunteers underwent T2-weighted MRI of the lumbar spine. Sagittal and axial T1- and T2-weighted images were acquired using parallel transmission MRI and conventional MRI. The percentage improvements in SNR and CNR were calculated, and statistical significance was determined using a two-tailed Student t test with p < 0.05 for significance. RESULTS. The CNR and SNR showed statistically significant improvements at all levels of the lumbar spine except SNR at T11 on axial T2-weighted imaging. For sagittal T1-weighted imaging, the average improvement with parallel transmission MRI was 53% in CNR and 19% in SNR. For axial T1-weighted imaging, the average improvement was 48% in CNR and 23% in SNR. For sagittal T2-weighted imaging, the average CNR improvement was 38% and the average SNR improvement, 20%. For axial T2-weighted scans, the average percentage improvement in CNR was greater than 100% and the average SNR improvement was 18% with parallel transmission MRI. CONCLUSION. The parallel transmission sequence improves image quality of lumbar spine MRI at 3 T, which is quantitatively supported by statistically significant improvements in SNR and CNR. C1 [Filippi, Christopher G.; Burbank, Heather N.; Alsofrom, Gary F.; Andrews, Trevor] Univ Vermont, Sch Med, Fletcher Allen Hlth Care, Dept Radiol, Burlington, VT 05401 USA. [Carlson, Morgan] Univ Washington, Sch Med, Dept Phys Rehabil & Med, Seattle, WA USA. [Johnson, Jason M.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Andrews, Trevor] Philips Healthcare, Cleveland, OH USA. RP Filippi, CG (reprint author), Univ Vermont, Sch Med, Fletcher Allen Hlth Care, Dept Radiol, 111 Colchester Ave,Patrick 1, Burlington, VT 05401 USA. EM christopher.filippi@vtmednet.org OI Andrews, Trevor/0000-0003-0331-1798 FU Department of Energy grant [SC 0001753] FX Some of the equipment used in this study is supported by Department of Energy grant SC 0001753. NR 19 TC 4 Z9 4 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 2012 VL 199 IS 4 BP 861 EP 867 DI 10.2214/AJR.11.8139 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 010TP UT WOS:000309117300039 PM 22997379 ER PT J AU Kung, JW Yablon, C Huang, ES Hennessey, H Wu, JS AF Kung, Justin W. Yablon, Corrie Huang, Edward S. Hennessey, Hooman Wu, Jim S. TI Clinical and Radiologic Predictive Factors of Septic Hip Arthritis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE hip aspiration; septic hip arthritis ID CONTRAST-MEDIA; TRANSIENT SYNOVITIS; BACTERIAL ARTHRITIS; PROSTHESIS; ASPIRATION; JOINT; ARTHROPLASTY; INFECTION; DIAGNOSIS; REVISION AB OBJECTIVE. The purpose of our study was to identify the clinical and radiologic factors associated with a positive culture during image-guided hip joint aspiration. MATERIALS AND METHODS. We performed a retrospective analysis of 167 consecutive hip aspirations for septic arthritis at a large tertiary medical center. Chart review was performed on the following clinical factors: serum WBC count >= 11 x 10(3) /mu L, serum erythrocyte sedimentation rate (ESR) >= 20 mm/h, C-reactive protein (CRP) >= 100 mg/ L, synovial fluid WBC count, synovial fluid polymorphonuclear (PMN) leukocytes >= 90%, fever, immunosuppression, antibiotic use, diabetes, presence of a prosthesis, and IV drug use (IVDU). Radiologic studies were reviewed for the following imaging and technical factors: presence of a sinus tract, fluid turbidity, volume of fluid (mL) aspirated, and whether the fluid analyzed was primarily aspirated or reaspirated after lavage. Logistic regression was used to calculate odds ratio (OR) and 95% CI. RESULTS. Of the 167 aspirations, 29 (17.4%) had positive cultures; 6 of 29 (20.7%) positive cultures occurred in reaspirated lavage fluid. On multivariate analysis using logistic regression with stepwise backward elimination, the significant clinical and radiologic predictors were elevated WBC (OR, 4.4; 95% CI, 1.1-17.3), high percentage of synovial fluid PMN leukocytes (OR, 10.6; 95% CI, 2.9-39.8), IVDU (OR, 9.0; 95% CI, 1.3-64.7), and fluid turbidity (OR, 20.5; 95% CI, 6.9-61.4). CONCLUSION. Positive hip cultures are associated with elevated serum WBC, IVDU, high percentage of synovial fluid PMN leukocytes, and fluid aspirate turbidity. Reaspiration of lavage fluid with either nonbacteriostatic saline or contrast material can yield positive cultures. C1 [Kung, Justin W.; Yablon, Corrie; Wu, Jim S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiol, Boston, MA 02215 USA. [Huang, Edward S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Hennessey, Hooman] McGill Univ, Fac Med, Ctr Hlth, Montreal, PQ, Canada. RP Kung, JW (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiol, 330 Brookline Ave, Boston, MA 02215 USA. EM jkung@bidmc.harvard.edu NR 25 TC 8 Z9 9 U1 3 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 2012 VL 199 IS 4 BP 868 EP 872 DI 10.2214/AJR.10.6273 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 010TP UT WOS:000309117300040 PM 22997380 ER PT J AU Duigenan, S Gee, MS AF Duigenan, Shauna Gee, Michael S. TI Imaging of Pediatric Patients With Inflammatory Bowel Disease SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE children; Crohn disease; CT enterography; inflammatory bowel disease; MR enterography ID MAGNETIC-RESONANCE ENTEROCLYSIS; CROHNS-DISEASE; CT ENTEROGRAPHY; ORAL CONTRAST; MR ENTEROGRAPHY; SMALL-INTESTINE; FOLLOW-THROUGH; TRANSABDOMINAL ULTRASONOGRAPHY; CONVENTIONAL ENTEROCLYSIS; COMPUTED-TOMOGRAPHY AB OBJECTIVE. The goal of this review is to examine the current imaging literature and develop basic imaging guidelines for evaluation of children with inflammatory bowel disease (IBD). The three following typical clinical scenarios in the imaging evaluation of IBD are considered: patient with an initial diagnosis of suspected IBD, the goals being to determine disease extent and severity and to differentiate Crohn disease from ulcerative colitis; patient with known IBD presenting with new acute symptoms (fever, peritonitis, leukocytosis) requiring urgent evaluation; and patient with known IBD presenting with nonacute symptomatic recurrence (abdominal pain, diarrhea), the goals being to assess the efficacy of the current treatment and to evaluate the possible need for additional medical or surgical intervention. CONCLUSION. Imaging of pediatric patients with IBD must balance considerations of diagnostic accuracy against concerns about patient exposure to ionizing radiation and tolerance of the imaging technique. The imaging modality chosen depends on the clinical presentation and expected pathologic finding. C1 [Gee, Michael S.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Gee, Michael S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Duigenan, Shauna] Ottawa Hosp, Dept Med Imaging, Ottawa, ON, Canada. RP Gee, MS (reprint author), Harvard Univ, Sch Med, Dept Radiol, 55 Fruit St,Ellison 237, Boston, MA 02114 USA. EM msgee@mgh.harvard.edu NR 69 TC 25 Z9 26 U1 0 U2 7 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 2012 VL 199 IS 4 BP 907 EP 915 DI 10.2214/AJR.11.7966 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 010TP UT WOS:000309117300046 PM 22997386 ER PT J AU Niell, B Specht, M Gerade, B Rafferty, E AF Niell, Bethany Specht, Michelle Gerade, Beverly Rafferty, Elizabeth TI Is Excisional Biopsy Required After a Breast Core Biopsy Yields Lobular Neoplasia? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE breast cancer; breast imaging; lobular carcinoma in situ; lobular neoplasia; pleomorphic lobular carcinoma in situ ID CARCINOMA-IN-SITU; MAMMOGRAPHIC FOLLOW-UP; FLAT EPITHELIAL ATYPIA; NEEDLE-BIOPSY; SURGICAL EXCISION; CLINICAL-SIGNIFICANCE; DUCTAL CARCINOMA; HYPERPLASIA; LESIONS; RISK AB OBJECTIVE. The management of lobular neoplasia (LN) on percutaneous core breast biopsies remains controversial. Published upgrade rates after surgical excision vary widely. This study aims to determine the frequency of malignancy following excision in patients with LN found on core biopsy. SUBJECTS AND METHODS. Our study identified patients from December 2005 through December 2010 with LN as the highest-risk lesion on core biopsy. Patients with flat epithelial atypia on core biopsy were not excluded. Per institutional policy, excision was routinely recommended. An upgrade from the core biopsy of LN was defined as excisional biopsy pathology that revealed ductal carcinoma in situ ( DCIS), invasive ductal carcinoma (IDC), or invasive lobular carcinoma (ILC). RESULTS. Between December 2005 and December 2010, 4472 percutaneous breast biopsies were performed, with 71 patients (1.5%) having LN as the highest-risk lesion on core biopsy. Sixty-seven patients (94%) underwent excision. The upgrade rate on excisional biopsy was 16% (11/67 patients), with the type of malignancy on excisional biopsy pathology as follows: DCIS, 36% (4/11); IDC, 18% (2/11); and ILC, 45% (5/11). All patients with pleomorphic lobular carcinoma in situ on core biopsy who proceeded to excision were upgraded to malignancy. After excluding patients with discordant results, patients with pleomorphic lobular carcinoma in situ, and patients with flat epithelial atypia on core biopsy, the upgrade rate of pure LN on excisional biopsy was 9%. CONCLUSION. LN on core biopsy warrants excisional biopsy given the upgrade rate to malignancy. C1 [Niell, Bethany; Specht, Michelle; Gerade, Beverly; Rafferty, Elizabeth] Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Boston, MA 02114 USA. RP Niell, B (reprint author), Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Wang Bldg,Ste 240, Boston, MA 02114 USA. EM bniell@partners.org NR 36 TC 22 Z9 22 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 2012 VL 199 IS 4 BP 929 EP 935 DI 10.2214/AJR.11.8447 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 010TP UT WOS:000309117300049 PM 22997389 ER PT J AU Salazar, GM Abujudeh, H AF Salazar, Gloria M. Abujudeh, Hani TI Quality Assurance in Interventional Radiology SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE complication threshold; interventional radiology; quality assurance; quality improvement; reporting systems ID VASC INTERV RADIOL; IMPROVEMENT GUIDELINES; COMPLICATIONS C1 [Salazar, Gloria M.; Abujudeh, Hani] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Abujudeh, H (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,GRB 290, Boston, MA 02114 USA. EM habujudeh@partners.org NR 13 TC 0 Z9 0 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 2012 VL 199 IS 4 BP W441 EP W443 DI 10.2214/AJR.11.8145 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 010TP UT WOS:000309117300002 PM 22997392 ER PT J AU Chiang, S Yip, S Betensky, RA Batten, JM Misdraji, J Iafrate, AJ AF Chiang, Sarah Yip, Stephen Betensky, Rebecca A. Batten, Julie M. Misdraji, Joseph Iafrate, A. John TI Identification of Tissue Contamination by Polymorphic Deletion Probe Fluorescence In Situ Hybridization SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE tissue misidentification; tissue contamination; laboratory error; polymorphism ID PARAFFIN-EMBEDDED TISSUE; SURGICAL PATHOLOGY; MICROSATELLITE MARKERS; EXTRANEOUS TISSUE; MIX-UPS; IDENTITY; PROVENANCE; SPECIMENS; DIAGNOSIS; SECTIONS AB Potential sources of error in surgical pathology include specimen misidentification, unidentified tissue, and tissue contamination of paraffin blocks and slides. Current molecular approaches to characterize unidentified or misidentified tissue include fluorescence in situ hybridization identification of sex chromosomes (XY FISH) and microsatellite analysis. Polymorphic deletion probe (PDP) FISH, a novel FISH assay based on copy number variants, can distinguish between cells and tissues from 2 individuals in situ, independent of gender. Using a panel of 3 PDPs, we compared the genotypes of potential tissue contaminants (n = 19) and unidentified tissues (n = 6) with patient tissues to determine the utility of PDP FISH in resolving specimen identity. XY FISH was added to increase the informative potential of the assay, and microsatellite analysis was used as a gold standard to confirm PDP FISH results. PDP FISH distinguished between putative contaminants and patient tissues in 13 of 14 cases and indicated a high likelihood of 2 tissues originating from the same source in 11 of 11 cases. The assay has a sensitivity and specificity of 86% [6/7, exact 95% confidence interval (CI): 42%, 97%] and 100% (9/9, exact 1-sided 97.5% CI: 68%, 100%), respectively, and a positive predictive value and negative predictive value of 100% (6/6, exact 1-sided 97.5% CI: 54%, 100%) and 90% (9/10, exact 95% CI: 55%, 98%), respectively. PDP FISH is an accurate and practical molecular assay for the genetic characterization of potential tissue contaminants and unidentified tissues, especially in the setting of small sample size, and permits concomitant assessment of morphology. C1 [Chiang, Sarah; Batten, Julie M.; Misdraji, Joseph; Iafrate, A. John] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Betensky, Rebecca A.] Harvard Univ, Sch Med, Dept Biostat, Boston, MA 02114 USA. [Yip, Stephen] BC Canc Agcy, Vancouver, BC, Canada. RP Iafrate, AJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Jackson 1015A, Boston, MA 02114 USA. EM aiafrate@partners.org NR 14 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 2012 VL 36 IS 10 BP 1464 EP 1471 DI 10.1097/PAS.0b013e31826247a2 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 010ST UT WOS:000309115100005 PM 22982889 ER PT J AU Kaplan, JS Schnitt, SJ Collins, LC Wang, YH Garber, JE Montgomery, K West, RB Krag, K Fetten, K Lincoln, A Tung, NM AF Kaplan, Jennifer S. Schnitt, Stuart J. Collins, Laura C. Wang, Yihong Garber, Judy E. Montgomery, Kelli West, Robert B. Krag, Karen Fetten, Katharina Lincoln, Anne Tung, Nadine M. TI Pathologic Features and Immunophenotype of Estrogen Receptor-positive Breast Cancers in BRCA1 Mutation Carriers SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE breast cancer; BRCA1; estrogen receptor ID BASAL EPITHELIAL PHENOTYPE; GERMLINE MUTATIONS; WOMEN; GRADE; POPULATION; CARCINOMAS; EXPRESSION; AGE AB Although most breast cancers in BRCA1 mutation carriers are estrogen receptor negative (ER-)with a basal-like phenotype, up to one third are ER positive (ER+). Little is known about the characteristics of this subgroup. To address this, we compared histologic and immunophenotypic features of 60 BRCA1-related ER+ breast cancers with those of 85 BRCA1-related ER- cancers and 174 matched ER+ sporadic cancers. ER+ BRCA1-related cancers were significantly less likely than ER- BRCA1-related cancers to be of pure invasive ductal type (P < 0.001) and to be of histologic grade 3 (P < 0.001), and less frequently to have a highmitotic rate (P < 0.001), pushing (or unknown) margins (P < 0.001), a moderate/marked lymphocytic infiltrate (P = 0.003), or geographic necrosis/fibrotic focus (P < 0.001). In addition, ER+ BRCA1-related cancers less often expressed CK5/6 (P < 0.0001), CK14 (P < 0.0001), and epidermal growth factor receptor (P < 0.0001) and more often expressed progesterone receptor (P < 0.0001). In contrast, when compared with ER+ sporadic cancers, ER+ BRCA1-related cancers were significantly more often of invasive ductal type (P = 0.005) and of histologic grade 3 (P = 0.006), more frequently had a high mitotic rate (P = 0.0003), and were more often CK14+ (P = 0.03). On unsupervised cluster analysis, some ER+ BRCA1 cancers clustered more closely with sporadic ER+ cancers, whereas others clustered more closely with ER- BRCA1-related cancers. Nuclear expression levels of poly(ADP) ribose polymerase 1 in ER+ BRCA1-related cancers were similar to those in ER- BRCA1-related cancers but significantly higher than in ER+ sporadic cancers. We conclude that ER+ BRCA1-related breast cancers show several morphologic and immunophenotypic differences from ER+ sporadic breast cancers as well as some similarities to ER- BRCA1-related cancers. C1 [Kaplan, Jennifer S.; Schnitt, Stuart J.; Collins, Laura C.; Wang, Yihong] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. [Fetten, Katharina; Lincoln, Anne; Tung, Nadine M.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. [Garber, Judy E.] Dana Farber Canc Inst, Div Populat Sci & Adult Oncol, Boston, MA 02115 USA. [Kaplan, Jennifer S.; Schnitt, Stuart J.; Collins, Laura C.; Wang, Yihong; Garber, Judy E.; Tung, Nadine M.] Harvard Univ, Sch Med, Boston, MA USA. [Krag, Karen] N Shore Med Ctr, Program Oncol, Danvers, MA USA. [Montgomery, Kelli; West, Robert B.] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA. RP Schnitt, SJ (reprint author), Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave, Boston, MA 02215 USA. EM sschnitt@bidmc.harvard.edu FU Breast Cancer Research Foundation FX Supported in part by a grant from the Breast Cancer Research Foundation to S.J.S. and N.M.T. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. NR 25 TC 7 Z9 7 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 2012 VL 36 IS 10 BP 1483 EP 1488 DI 10.1097/PAS.0b013e31825789ed PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 010ST UT WOS:000309115100008 PM 22613997 ER PT J AU Lee, CH Ali, RH Rouzbahman, M Marino-Enriquez, A Zhu, MJ Guo, XQ Brunner, AL Chiang, S Leung, S Nelnyk, N Huntsman, DG Gilks, CB Nielsen, TO Dal Cin, P van de Rijn, M Oliva, E Fletcher, JA Nucci, MR AF Lee, Cheng-Han Ali, Rola H. Rouzbahman, Marjan Marino-Enriquez, Adrian Zhu, Meijun Guo, Xiangqian Brunner, Alayne L. Chiang, Sarah Leung, Samuel Nelnyk, Nataliya Huntsman, David G. Gilks, C. Blake Nielsen, Torsten O. Dal Cin, Paola van de Rijn, Matt Oliva, Esther Fletcher, Jonathan A. Nucci, Marisa R. TI Cyclin D1 as a Diagnostic Immunomarker for Endometrial Stromal Sarcoma With YWHAE-FAM22 Rearrangement SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE endometrial stromal sarcoma; YWHAE-FAM22; cyclin D1; JAZF1-SUZ12; uterine sarcoma ID PRIMITIVE NEUROECTODERMAL TUMOR; JAZF1-JJAZ1 GENE FUSION; SMOOTH-MUSCLE DIFFERENTIATION; MANTLE CELL LYMPHOMA; HIGH-GRADE SARCOMAS; REGULATORY PROTEINS; BETA-CATENIN; PROGNOSTIC-SIGNIFICANCE; EXPRESSION; UTERUS AB Endometrial stromal sarcoma (ESS) characterized by YWHAE-FAM22 genetic fusion is histologically higher grade and clinically more aggressive than ESS with JAZF1-SUZ12 or equivalent genetic rearrangements, hence it is clinically important to recognize this subset of ESS. To identify diagnostic immunomarkers for this biologically defined ESS subset, we compared gene expression profiles between YWHAE-FAM22 ESS and JAZF1-rearranged ESS. These studies showed consistent upregulation of cyclin D1 in YWHAE-FAM22 ESS compared with JAZF1-SUZ12 ESS. Immunohistochemically, the high-grade round cell component of all 12 YWHAE-FAM22 ESS demonstrated diffuse (>= 70%) moderate to strong nuclear cyclin D1 staining, and this diffuse positivity was not seen in 34 ESSs with JAZF1 and equivalent genetic rearrangements or in 21 low-grade ESS with no demonstrable genetic rearrangements. In a series of 243 non-ESS pure uterine mesenchymal and mixed epithelial-mesenchymal tumors, only 2 of 8 undifferentiated endometrial sarcomas with nuclear uniformity and 1 of 80 uterine leiomyosarcomas demonstrate diffuse cyclin D1 immunoreactivity. Both cyclin D1-positive undifferentiated endometrial sarcomas showed diffuse strong CD10 staining, which is consistently absent in the high-grade round cell component of YWHAE-FAM22 ESS. The low-grade spindle cell component of YWHAE-FAM22 ESS showed a spatially heterogenous cyclin D1 staining pattern that was weaker and less diffuse overall. Our findings indicate that cyclin D1 is a sensitive and specific diagnostic immunomarker for YWHAE-FAM22 ESS. When evaluating high-grade uterine sarcomas, cyclin D1 can be included in the immunohistochemical panel as an indicator of YWHAE-FAM22 ESS. C1 [Lee, Cheng-Han; Ali, Rola H.; Leung, Samuel; Gilks, C. Blake; Nielsen, Torsten O.] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada. [Lee, Cheng-Han] Vancouver Gen Hosp, Genet Pathol Evaluat Ctr, Dept Pathol & Lab Med, Vancouver, BC V5Z 4E3, Canada. [Nelnyk, Nataliya; Huntsman, David G.] British Columbia Canc Agcy, CTAG, Vancouver, BC V5Z 4E6, Canada. [Marino-Enriquez, Adrian; Zhu, Meijun; Dal Cin, Paola; Fletcher, Jonathan A.; Nucci, Marisa R.] Toronto Gen Hosp, Dept Pathol, Toronto, ON, Canada. [Rouzbahman, Marjan; Nucci, Marisa R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Chiang, Sarah; Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Guo, Xiangqian; Brunner, Alayne L.; van de Rijn, Matt] Stanford Univ, Med Ctr, Dept Pathol, Stanford, CA 94305 USA. RP Nucci, MR (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St,Amory 3, Boston, MA 02115 USA. EM mnucci@partners.org OI Ali, Rola/0000-0001-5747-8900 FU Department of Pathology and Laboratory Medicine at the University of British Columbia; Fundacion Alfonso Martin Escudero, Madrid, Spain; NIH [CA112270] FX C-H.L. is supported by funds from the Department of Pathology and Laboratory Medicine at the University of British Columbia. A.M-E. is supported by a research grant from Fundacion Alfonso Martin Escudero, Madrid, Spain. The gene expression analysis is supported by NIH grant CA112270. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. NR 40 TC 52 Z9 55 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 2012 VL 36 IS 10 BP 1562 EP 1570 DI 10.1097/PAS.0b013e31825fa931 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 010ST UT WOS:000309115100018 PM 22982899 ER PT J AU Stahl, D Eikermann, M AF Stahl, D. Eikermann, M. TI Is the Blood Loss Score universally acceptable? Reply SO ANAESTHESIA LA English DT Letter C1 [Stahl, D.; Eikermann, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Stahl, D (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM dstahl@partners.org NR 3 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0003-2409 J9 ANAESTHESIA JI Anaesthesia PD OCT PY 2012 VL 67 IS 10 BP 1180 EP 1181 DI 10.1111/j.1365-2044.2012.07324.x PG 2 WC Anesthesiology SC Anesthesiology GA 000PG UT WOS:000308398500029 ER PT J AU Wambua, DM Tannous, BA Chiu, NHL AF Wambua, Dickson M. Tannous, Bakhos A. Chiu, Norman H. L. TI Creating mass signatures for the detection of microRNA SO ANALYTICAL METHODS LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CANCER; SPECTROMETRY; DEREGULATION; MIRBASE; SINGLE; RNAS AB MicroRNAs (miRNAs) play a crucial role in the post-transcriptional regulation of gene expression, and have already been associated with 160+ diseases. With the small sizes of miRNAs (19-25 nt) and the increasing number of human miRNAs (>2000) being reported, the accurate detection of a specific miRNA has continued to be a challenging issue. In this report, a new concept for improving the accuracy of direct mass spectrometric (MS) measurements of miRNAs is introduced. The concept aims at creating a unique signature in the mass spectrum of miRNA. To achieve this goal, one way is to capture a specific miRNA by using a complementary DNA probe. The miRNA is then eluted and digested with a specific endonuclease. The digested miRNA fragments are directly measured by using MS. The multiple peaks that correspond to the digested miRNA fragments are collectively defined as a mass signature of the miRNA being analyzed. Since the peak pattern is dependent on the intrinsic property, i.e. RNA sequence, of a specific miRNA, it is referred to as an intrinsic mass signature. Alternatively, a unique mass signature can be created by incorporating one or more extra nucleotides into the 30 end of miRNA and the extended miRNA is measured by using MS. The molecular mass of the extended miRNA, which is defined as an extended mass signature, is expected to be different from the other miRNAs within the same sample. In comparison to matching the measured molecular mass of an undigested or unextended miRNA molecule to the expected molecular mass, the two different approaches to create a unique mass signature can improve the accuracy on qualitative MS detection of a specific miRNA. C1 [Wambua, Dickson M.; Chiu, Norman H. L.] Univ N Carolina, Dept Chem & Biochem, Greensboro, NC 27412 USA. [Tannous, Bakhos A.] Massachusetts Gen Hosp, Mol Neurogenet Unit, Dept Neurol, Boston, MA 02129 USA. [Tannous, Bakhos A.] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Chiu, Norman H. L.] Joint Sch Nanosci & Nanoengn, Dept Nanosci, Greensboro, NC 27401 USA. RP Chiu, NHL (reprint author), Univ N Carolina, Dept Chem & Biochem, 410 Patricia A Sullivan Sci Bldg,301 McIver St, Greensboro, NC 27412 USA. EM prof.chiu@gmail.com FU NSF GK-12 program; Department of Chemistry and Biochemistry at UNCG; NSF Major Research Instrumentation Grant [0420292] FX The authors wish to thank the NSF GK-12 program and the Department of Chemistry and Biochemistry at UNCG for the financial support. The MALDI-TOF MS instrument was purchased with a NSF Major Research Instrumentation Grant (award #0420292). NR 27 TC 3 Z9 4 U1 1 U2 13 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1759-9660 J9 ANAL METHODS-UK JI Anal. Methods PD OCT PY 2012 VL 4 IS 10 BP 3453 EP 3459 DI 10.1039/c2ay25504a PG 7 WC Chemistry, Analytical; Food Science & Technology; Spectroscopy SC Chemistry; Food Science & Technology; Spectroscopy GA 012LS UT WOS:000309238300059 ER PT J AU Colombo, C Ronellenfitsch, U Yuxin, Z Rutkowski, P Miceli, R Bylina, E Hohenberger, P Raut, CP Gronchi, A AF Colombo, C. Ronellenfitsch, U. Yuxin, Z. Rutkowski, P. Miceli, R. Bylina, E. Hohenberger, P. Raut, C. P. Gronchi, A. TI Clinical, Pathological and Surgical Characteristics of Duodenal Gastrointestinal Stromal Tumor and Their Influence on Survival: A Multi-Center Study SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID IMATINIB MESYLATE; ADJUVANT IMATINIB; RANDOMIZED-TRIAL; COX REGRESSION; MANAGEMENT; LIKELIHOOD; DIAGNOSIS; RISK AB The duodenum is a rare site of primary gastrointestinal stromal tumor (GIST). Overall (OS) and disease-free survival (DFS) after limited resection (LR) versus pancreaticoduodenectomy (PD) were studied. All patients who underwent surgery for primary, localized duodenal GIST between 2000 and 2011 were identified from four prospective institutional databases. OS and DFS were calculated by Kaplan-Meier method. Univariate analysis was performed. Eighty-four patients (median follow-up 42 months) underwent LR (n = 56, 67 %) or PD (n = 28, 33 %). Patients in the PD group had a larger median tumor size (7 cm vs. 5 cm, p = 0.024) and higher mitotic count (39 % vs. 19 % > 5/50 high-power fields, p = 0.05). Complications were observed in five patients (9 %) in the LR group and ten patients (36 %) in the PD group. OS and DFS for the entire cohort were 89 % and 64 % at 5 years, respectively. No difference in outcome between LR and PD were observed. Eleven patients were treated with preoperative IM. A major RECIST response was obtained in nine (80 %), whereas two had stable disease. Twenty-three patients received postoperative Imatinib (IM). A trend toward a better OS in IM-treated patients could be detected only in the high-risk group. Type of duodenal resection does not impact outcome. The choice should be determined by duodenal site of origin and tumor size. IM may be considered in cases at high risk of recurrence; in neoadjuvant setting, IM might facilitate resection and possibly increase the chance of preserving normal biliary and pancreatic anatomy. C1 [Colombo, C.; Gronchi, A.] Fdn IRCCS Ist Nazl Tumori, Dept Surg, Sarcoma Serv, Milan, Italy. [Ronellenfitsch, U.; Hohenberger, P.] Mannheim Univ Med, Div Surg Oncol & Thorac Surg, Mannheim, Germany. [Yuxin, Z.; Raut, C. P.] Brigham & Womens Hosp, Dept Surg, Ctr Sarcoma & Bone Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Yuxin, Z.; Raut, C. P.] Harvard Univ, Sch Med, Boston, MA USA. [Yuxin, Z.] Chinese Acad Med Sci, Dept Surg, Canc Hosp, Beijing 100730, Peoples R China. [Rutkowski, P.; Bylina, E.] Maria Sklodowska Curie Mem Canc Ctr & Inst Oncol, Dept Soft Tissue Bone Sarcoma & Melanoma, Warsaw, Poland. [Miceli, R.] Fdn IRCCS Ist Nazl Tumori, Unit Med Stat Biometry & Bioinformat, Milan, Italy. RP Colombo, C (reprint author), Fdn IRCCS Ist Nazl Tumori, Dept Surg, Sarcoma Serv, Milan, Italy. EM alessandro.gronchi@istitutotumori.mi.it RI Miceli, Rosalba/C-1215-2017; Colombo, Chiara/C-4303-2017; OI Miceli, Rosalba/0000-0003-0954-375X; Colombo, Chiara/0000-0001-8031-5528; Gronchi, Alessandro/0000-0002-4703-3534; Rutkowski, Piotr/0000-0002-8920-5429 NR 24 TC 15 Z9 18 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD OCT PY 2012 VL 19 IS 11 BP 3361 EP 3367 DI 10.1245/s10434-012-2559-0 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA 005FY UT WOS:000308737100012 PM 22843188 ER PT J AU Ito, T Hiramatsu, K Tomasz, A de Lencastre, H Perreten, V Holden, MTG Coleman, DC Goering, R Giffard, PM Skov, RL Zhang, KY Westh, H O'Brien, F Tenover, FC Oliveira, DC Boyle-Vavra, S Laurent, F Kearns, AM Kreiswirth, B Ko, KS Grundmann, H Sollid, JE John, JF Daum, R Soderquist, B Buist, G AF Ito, Teruyo Hiramatsu, Keiichi Tomasz, Alexander de Lencastre, Herminia Perreten, Vincent Holden, Matthew T. G. Coleman, David C. Goering, Richard Giffard, Philip M. Skov, Robert L. Zhang, Kunyan Westh, Henrik O'Brien, Frances Tenover, Fred C. Oliveira, Duarte C. Boyle-Vavra, Susan Laurent, Frederic Kearns, Angela M. Kreiswirth, Barry Ko, Kwan Soo Grundmann, Hajo Sollid, Johanna E. John, Joseph F., Jr. Daum, Robert Soderquist, Bo Buist, Girbe CA Int Working Grp Classification Sta TI Guidelines for Reporting Novel mecA Gene Homologues SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Editorial Material ID RESISTANT STAPHYLOCOCCUS-AUREUS; PENICILLIN-BINDING PROTEIN; METHICILLIN-RESISTANT; SEQUENCE ALIGNMENT; MOLECULAR-CLONING; SCIURI; DETERMINANTS; NOMENCLATURE; EVOLUTION; STRAINS C1 [Ito, Teruyo; Hiramatsu, Keiichi] Juntendo Univ, Dept Bacteriol, Tokyo, Japan. [Tomasz, Alexander; de Lencastre, Herminia] Rockefeller Univ, New York, NY 10021 USA. [de Lencastre, Herminia; Oliveira, Duarte C.] Univ Nova Lisboa, Inst Tecnol Quim & Biol, Oeiras, Portugal. [Perreten, Vincent] Univ Bern, Inst Vet Bacteriol, Bern, Switzerland. [Holden, Matthew T. G.] Wellcome Trust Sanger Inst, Hinxton, Cambs, England. [Coleman, David C.] Univ Dublin, Dublin Dent Univ Hosp, Trinity Coll Dublin, Dublin, Ireland. [Goering, Richard] Creighton Univ, Med Ctr, Omaha, NE USA. [Giffard, Philip M.] Charles Darwin Univ, Menzies Sch Hlth Res, Darwin, NT 0909, Australia. [Skov, Robert L.] Statens Serum Inst, DK-2300 Copenhagen, Denmark. [Zhang, Kunyan] Univ Calgary, Calgary, AB, Canada. [Westh, Henrik] Univ Copenhagen, Fac Hlth, Copenhagen, Denmark. [Westh, Henrik] Univ Copenhagen, Hvidovre Hosp, Copenhagen, Denmark. [O'Brien, Frances] Curtin Univ Technol, Perth, WA, Australia. [Tenover, Fred C.] Cepheid, Sunnyvale, CA USA. [Oliveira, Duarte C.] Univ Nova Lisboa, Fac Ciencias & Tecnol, Dept Life Sci, CREM, Caparica, Portugal. [Boyle-Vavra, Susan; Daum, Robert] Univ Chicago, Chicago, IL 60637 USA. [Laurent, Frederic] Hosp Civils Lyon, French Natl Reference Ctr Staphylococci, Lyon, France. [Kearns, Angela M.] Hlth Protect Agcy, Staphylococcus Reference Unit, London, England. [Kreiswirth, Barry] Publ Hlth Res Inst, New York, NY USA. [Ko, Kwan Soo] Sungkyunkwan Univ, Sch Med, Seoul, South Korea. [Grundmann, Hajo] Natl Inst Publ Hlth & Environm, Utrecht, Netherlands. [Sollid, Johanna E.] Univ Tromso, Tromso, Norway. [John, Joseph F., Jr.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Soderquist, Bo] Orebro Univ Hosp, Orebro, Sweden. [Buist, Girbe] Univ Groningen, Groningen, Netherlands. [Buist, Girbe] Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. RP Ito, T (reprint author), Juntendo Univ, Dept Bacteriol, Tokyo, Japan. EM teruybac@juntendo.ac.jp RI Coleman, David/C-2008-2009; Giffard, Philip/N-2293-2013; Staves, Peter/C-8219-2014; Laurent, Frederic/M-4719-2014; Holden, Matthew/K-6449-2014; OI Ko, Kwan Soo/0000-0002-0978-1937; Coleman, David/0000-0003-1797-2888; Holden, Matthew/0000-0002-4958-2166; de Lencastre, Herminia/0000-0001-6816-8932; Westh, Henrik/0000-0001-5681-647X; Oliveira, Duarte/0000-0002-9591-1039; Goering, Richard/0000-0001-7502-7185; Tomasz, Alexander/0000-0003-1520-1983 FU NIAID NIH HHS [R01 AI045738] NR 21 TC 67 Z9 71 U1 1 U2 18 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 2012 VL 56 IS 10 BP 4997 EP 4999 DI 10.1128/AAC.01199-12 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 006GQ UT WOS:000308807900001 PM 22869575 ER PT J AU Inamoto, Y Martin, PJ Chai, XY Jagasia, M Palmer, J Pidala, J Cutler, C Pavletic, SZ Arora, M Jacobsohn, D Carpenter, PA Flowers, MED Khera, N Vogelsang, GB Weisdorf, D Storer, BE Lee, SJ AF Inamoto, Yoshihiro Martin, Paul J. Chai, Xiaoyu Jagasia, Madan Palmer, Jeanne Pidala, Joseph Cutler, Corey Pavletic, Steven Z. Arora, Mukta Jacobsohn, David Carpenter, Paul A. Flowers, Mary E. D. Khera, Nandita Vogelsang, Georgia B. Weisdorf, Daniel Storer, Barry E. Lee, Stephanie J. CA Chronic GVHD Consortium TI Clinical Benefit of Response in Chronic Graft-versus-Host Disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Allogeneic; Hematopoietic cell transplantation; National Institutes of Health; Response criteria ID QUALITY-OF-LIFE; CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; BONE-MARROW-TRANSPLANTATION; CELL TRANSPLANTATION; CHRONIC GVHD; EXTRACORPOREAL PHOTOPHERESIS; END-POINTS; CRITERIA; TRIALS AB To determine whether changes in objective response measures proposed by the National Institutes of Health correlate with clinical benefit, such as symptom burden, quality of life, and survival outcomes, we analyzed data from a multicenter prospective cohort of 283 patients with chronic graft-versus-host disease requiring systemic treatment. The median follow-up time of survivors was 25.1 months (range, 5.4-47.7 months) after enrollment. Symptom measures included the Lee symptom scale and 10-point patient-reported symptoms. Quality-of-life measures included the Short Form-36, Functional Assessment of Cancer Therapy Bone Marrow Transplantation, and Human Activities Profile. Overall and organ-specific responses were calculated by comparing manifestations at the 6-month visit and those at the enrollment visit using a provisional algorithm. Complete or partial responses were considered "response," and stable or progressive disease was considered "no response." Overall response rate at 6 months was 32%. Organ-specific response rates were 45% for skin, 23% for eyes, 32% for mouth, and 51% for gastrointestinal tract. Response at 6 months, as calculated according to the provisional response algorithm, was correlated with changes in symptom burden in patients with newly diagnosed chronic graft-versus-host disease, but not with changes in quality of life or survival outcomes. Modification of the algorithm or validation of other more meaningful clinical endpoints is warranted for future clinical trials of treatment for chronic graft-versus-host disease. Biol Blood Marrow Transplant 18: 1517-1524 (2012) (C) 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved. C1 [Inamoto, Yoshihiro; Martin, Paul J.; Chai, Xiaoyu; Carpenter, Paul A.; Flowers, Mary E. D.; Khera, Nandita; Storer, Barry E.; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Jagasia, Madan] Vanderbilt Univ, Med Ctr, Hematol & Stem Cell Transplant Program, Nashville, TN USA. [Palmer, Jeanne] Med Coll Wisconsin, Div Hematol Oncol, Milwaukee, WI 53226 USA. [Pidala, Joseph] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pavletic, Steven Z.] NCI, Bethesda, MD 20892 USA. [Arora, Mukta; Weisdorf, Daniel] Univ Minnesota, Blood & Marrow Transplant Program, Minneapolis, MN USA. [Jacobsohn, David] Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Div Blood & Marrow Transplantat, Washington, DC 20010 USA. [Vogelsang, Georgia B.] Johns Hopkins Univ Hosp, Dept Oncol, Baltimore, MD 21287 USA. RP Inamoto, Y (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, D5-290,1100 Fairview Ave N, Seattle, WA 98109 USA. EM yinamoto@fhcrc.org FU National Institutes of Health [CA118953, CA163438]; Japan Society for the Promotion of Science FX This work was supported by National Institutes of Health grants CA118953 and CA163438. Y.I. is a recipient of a Japan Society for the Promotion of Science Postdoctoral Fellowship for Research Abroad. The authors have no conflicts of interest to disclose. NR 37 TC 15 Z9 16 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD OCT PY 2012 VL 18 IS 10 BP 1517 EP 1524 DI 10.1016/j.bbmt.2012.05.016 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 013OG UT WOS:000309314100008 PM 22683612 ER PT J AU Castellarin, P Stevenson, K Biasotto, M Yuan, A Woo, SB Treister, NS AF Castellarin, Paolo Stevenson, Kristen Biasotto, Matteo Yuan, Anna Woo, Sook-Bin Treister, Nathaniel Simon TI Extensive Dental Caries in Patients with Oral Chronic Graft-versus-Host Disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Oral cavity; Stem cell transplantation; Oral complications ID BONE-MARROW-TRANSPLANTATION; SALIVARY-GLAND INVOLVEMENT; HEMATOPOIETIC-CELL TRANSPLANTATION; FOLLOW-UP; RECIPIENTS; COMPLICATIONS; DIAGNOSIS; LEUKEMIA AB The oral cavity is one of the sites most frequently affected by chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic cell transplantation (alloHCT) and can be a significant source of patient morbidity due to both mucosal and salivary gland involvement. The development of dental decay is a potentially devastating oral complication that has only rarely been reported in the transplantation literature. The purpose of this study was to comprehensively characterize a cohort of patients with cGVHD who subsequently developed extensive dental caries. A retrospective case-record review was conducted for patients who had undergone alloHCT at Dana-Farber/Brigham and Women's Cancer Center between 1990 and 2010 and developed cGVHD-associated rampant dental decay. All patients underwent dental evaluation, involving soft and hard tissue examination and dental radiography, before and after alloHCT. Any dental caries diagnosed at the pre-alloHCT evaluation were treated definitively, such that all patients were considered free of caries at the time of admission for alloHCT. A total of 21 patients were identified, with a median time of cGVHD onset of 5.4 months (range, 2.2-18.5 months) after alloHCT. All patients were diagnosed with oral cGVHD, with 90% demonstrating mucosal involvement and 95% demonstrating salivary gland involvement. Post-alloHCT dental evaluation was performed at a median of 22 months (range, 4-81) after alloHCT, when 10 patients were diagnosed with gross caries and 8 patients had 4 or more affected teeth. Cervical and interproximal patterns of dental caries were frequently diagnosed. The proportions of patients with gross caries, one surface caries, and more than one surface caries (classified as 0, 1-3, and >= 4, respectively) were significantly higher after alloHCT than before alloHCT, with at least 50% of patients experiencing an increase. Patients with oral cGVHD who were free of caries at the time of transplantation developed extensive areas of cervical decay at a median of less than 2 years after alloHCT. This is the first comprehensive characterization of this severe late complication of alloHCT and oral cGVHD. Greater awareness by transplantation oncologists and dentists, as well as more aggressive preventive measures, are needed, as are further prospective studies to better elucidate the incidence of this complication, identify risk factors, and evaluate the effectiveness of preventive interventions. Biol Blood Marrow Transplant IS: 1573-1579 (2012) (C) 2012 American Society for Blood and Marrow Transplantation C1 [Yuan, Anna; Woo, Sook-Bin; Treister, Nathaniel Simon] Brigham & Womens Hosp, Div Oral Med & Dent, Boston, MA 02120 USA. [Castellarin, Paolo; Biasotto, Matteo] Univ Trieste, Dept Dent Sci, Trieste, Italy. [Stevenson, Kristen] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Woo, Sook-Bin; Treister, Nathaniel Simon] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Treister, NS (reprint author), Brigham & Womens Hosp, Div Oral Med & Dent, 1620 Tremont St,BC-3-028, Boston, MA 02120 USA. EM ntreister@partners.org OI BIASOTTO, Matteo/0000-0001-6024-6115 NR 28 TC 10 Z9 11 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD OCT PY 2012 VL 18 IS 10 BP 1573 EP 1579 DI 10.1016/j.bbmt.2012.04.009 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 013OG UT WOS:000309314100014 PM 22516054 ER PT J AU McDermott, DF Drake, CG Sznol, M Choueiri, TK Powderly, JD Smith, DC Wigginton, JM Kollia, G Gupta, A Atkins, MB AF McDermott, D. F. Drake, C. G. Sznol, M. Choueiri, T. K. Powderly, J. D. Smith, D. C. Wigginton, J. M. Kollia, G. Gupta, A. Atkins, M. B. TI Clinical activity and safety of anti-programmed death-1 (PD-1) (BMS-936558/MDX-1106/ONO-4538) in patients (pts) with previously treated, metastatic renal cell carcinoma (mRCC) SO BJU INTERNATIONAL LA English DT Meeting Abstract CT 11th International Kidney Cancer Symposium CY OCT 05-06, 2012 CL Chicago, IL C1 [McDermott, D. F.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Drake, C. G.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Sznol, M.] Yale Canc Ctr, New Haven, CT USA. [Choueiri, T. K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol,Brigham & Womens Hos, Boston, MA 02115 USA. [Powderly, J. D.] Carolina Biooncol Inst, Huntersville, NC USA. [Smith, D. C.] Univ Michigan, Ann Arbor, MI 48109 USA. [Wigginton, J. M.; Kollia, G.; Gupta, A.] Bristol Myers Squibb Co, Princeton, NJ USA. [Atkins, M. B.] Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 J9 BJU INT JI BJU Int. PD OCT PY 2012 VL 110 SU 2 SI SI MA 09 BP 4 EP 4 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 008BO UT WOS:000308932400010 ER PT J AU Ehrlich, PF Cost, NG Khanna, G Mullen, EA Gratias, EJ Naranjo, A Dome, JS Perlman, EJ Geller, JI AF Ehrlich, P. F. Cost, N. G. Khanna, G. Mullen, E. A. Gratias, E. J. Naranjo, A. Dome, J. S. Perlman, E. J. Geller, J. I. TI A description of the surgical experience in children, adolescents and young adults with renal cell carcinoma: a report from the Children's Oncology Group Study AREN 03B2 SO BJU INTERNATIONAL LA English DT Meeting Abstract CT 11th International Kidney Cancer Symposium CY OCT 05-06, 2012 CL Chicago, IL C1 [Ehrlich, P. F.] Univ Michigan, CS Mott Childrens Hosp, Dept Surg, Sect Pediat Surg,Sch Med, Ann Arbor, MI 48109 USA. [Cost, N. G.] Cincinnati Childrens Hosp Med Ctr, Div Pediat Urol, Cincinnati, OH USA. [Khanna, G.] Washington Univ, Sch Med, Edward Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. [Mullen, E. A.] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Gratias, E. J.] Univ Tennessee, Coll Med Chattanooga, TC Thompson Childrens Hosp, Div Pediat Hematol Oncol, Chattanooga, TN USA. [Naranjo, A.] Univ Florida, Childrens Oncol Grp Stat & Data Ctr, Dept Biostat, Gainesville, FL USA. [Dome, J. S.] Childrens Natl Med Ctr, Div Pediat Oncol, Washington, DC 20010 USA. [Perlman, E. J.] Northwestern Univ, Dept Pathol, Feinberg Sch Med, Dept Pathol,Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. [Geller, J. I.] Cincinnati Childrens Hosp Med Ctr, Div Pediat Oncol, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1464-4096 J9 BJU INT JI BJU Int. PD OCT PY 2012 VL 110 SU 2 SI SI MA 39 BP 18 EP 18 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 008BO UT WOS:000308932400040 ER PT J AU Erickson, MA Hansen, K Banks, WA AF Erickson, Michelle A. Hansen, Kim Banks, William A. TI Inflammation-induced dysfunction of the low-density lipoprotein receptor-related protein-1 at the blood-brain barrier: Protection by the antioxidant N-acetylcysteine SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE Amyloid beta; Alzheimer's disease; Neuroinflammation; Oxidative stress; Lipopolysaccharide; LRP-1; Pgp; N-acetylcysteine ID AMYLOID-BETA-PEPTIDE; MICROVASCULAR ENDOTHELIAL-CELLS; MILD COGNITIVE IMPAIRMENT; P-GLYCOPROTEIN FUNCTION; NECROSIS-FACTOR-ALPHA; ACETYL-L-CYSTEINE; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; METABOLIC SYNDROME; SYSTEMIC INFLAMMATION AB Impairment in two blood-brain barrier (BBB) efflux transporters, p-glycoprotein (Pgp) and low-density lipoprotein receptor-related protein-1 (LRP-1) are thought to contribute to the progression of Alzheimer's disease (AD) by resulting in the brain accumulation of their substrate amyloid beta peptide (A beta). The initial cause of impaired efflux, however, is unknown. We have shown that induction of systemic inflammation by intraperitoneal administration of lipopolysaccharide impairs the efflux of A beta from the brain, suggesting that systemic inflammation could be one such initiator. In this study, we determined whether pre-administration of the antioxidant N-aceytlcysteine (Nac) has a protective effect against LPS-induced A beta transporter dysfunction. Our findings were that Nac protected against LPS-induced A beta transport dysfunction at the BBB through an LRP-1-dependent and Pgp-independent mechanism. This was associated with Nac exerting antioxidant effects in the periphery but not the brain, despite an increased rate of entry of Nac into the brain following LPS. We also found that Nac pre-administration resulted in lower blood levels of the cytokines and chemokines interferon-gamma, interleukin-10, CCL2, CCL4, and CCL5, but only lowered CCL4 in the cerebral cortex and hippocampus. Finally, we observed that hippocampal cytokine responses to LPS were decreased compared to cortex. These findings demonstrate a novel mechanism by which antioxidants prevent A beta accumulation in the brain caused by inflammation, and therefore protect against AD. (c) 2012 Elsevier Inc. All rights reserved. C1 [Erickson, Michelle A.] St Louis Univ, Dept Physiol & Pharmacol, St Louis, MO 63103 USA. [Erickson, Michelle A.; Hansen, Kim; Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, GRECC, Seattle, WA USA. [Hansen, Kim; Banks, William A.] Univ Washington, Sch Med, Dept Internal Med, Div Gerontol & Geriatr Med, Seattle, WA USA. RP Banks, WA (reprint author), Bldg 1,Rm 810A,1660 Columbian Way, Seattle, WA 98108 USA. EM mericks9@slu.edu; nesnah@washington.edu; wabanks1@uw.edu FU NIA NIH HHS [R01 AG029839] NR 73 TC 30 Z9 31 U1 3 U2 20 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1591 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD OCT PY 2012 VL 26 IS 7 BP 1085 EP 1094 DI 10.1016/j.bbi.2012.07.003 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 007PC UT WOS:000308899600011 PM 22809665 ER PT J AU Bender, BC Schaedeli-Stark, F Koch, R Joshi, A Chu, YW Rugo, H Krop, IE Girish, S Friberg, LE Gupta, M AF Bender, Brendan C. Schaedeli-Stark, Franziska Koch, Reinhold Joshi, Amita Chu, Yu-Waye Rugo, Hope Krop, Ian E. Girish, Sandhya Friberg, Lena E. Gupta, Manish TI A population pharmacokinetic/pharmacodynamic model of thrombocytopenia characterizing the effect of trastuzumab emtansine (T-DM1) on platelet counts in patients with HER2-positive metastatic breast cancer SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Trastuzumab emtansine; T-DM1; Thrombocytopenia; Population pharmacokinetic/pharmacodynamic model; Semimechanistic; Cumulative TCP ID PHASE-I; CANTUZUMAB MERTANSINE; MYELOSUPPRESSION; CHEMOTHERAPY; CARBOPLATIN; TOXICITY; ANTIGEN AB Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate in the development for the treatment of human epidermal growth factor receptor 2-positive cancers. Thrombocytopenia (TCP) is the dose-limiting toxicity of T-DM1. A semimechanistic population pharmacokinetic/pharmacodynamic (PK/PD) model was developed to characterize the effect of T-DM1 on patient platelet counts. A PK/PD model with transit compartments that mimic platelet development and circulation was fit to concentration-platelet-time course data from two T-DM1 single-agent studies (TDM3569g; N = 52 and TDM4258g; N = 112). NONMEMA (R) 7 software was used for model development. Data from a separate phase II study (TDM4374g; N = 110) were used for model evaluation. Patient baseline characteristics were evaluated as covariates of model PD parameters. The model described the platelet data well and predicted the incidence of grade a parts per thousand yen3 TCP. The model predicted that with T-DM1 3.6 mg/kg given every 3 weeks (q3w), the lowest platelet nadir would occur after the first dose. Also predicted was a patient subgroup (46 %) having variable degrees of downward drifting platelet-time profiles, which were predicted to stabilize by the eighth treatment cycle to platelet counts above grade 3 TCP. Baseline characteristics were not significant covariates of PD parameters in the model. This semimechanistic PK/PD model accurately captures the cycle 1 platelet nadir, the downward drift noted in some patient platelet-time profiles, and the similar to 8 % incidence of grade a parts per thousand yen3 TCP with T-DM1 3.6 mg/kg q3w. This model supports T-DM1 3.6 mg/kg q3w as a well-tolerated dose with minimal dose delays or reductions for TCP. C1 [Bender, Brendan C.; Joshi, Amita; Chu, Yu-Waye; Girish, Sandhya; Gupta, Manish] Genentech Inc, San Francisco, CA 94080 USA. [Bender, Brendan C.; Friberg, Lena E.] Uppsala Univ, Dept Pharmaceut Biosci, Uppsala, Sweden. [Schaedeli-Stark, Franziska; Koch, Reinhold] F Hoffman La Roche Ltd, Basel, Switzerland. [Rugo, Hope] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Krop, Ian E.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Girish, S (reprint author), Genentech Inc, San Francisco, CA 94080 USA. EM brendan.bender@farmbio.uu.se; girish.sandhya@gene.com FU Genentech, Inc. FX The study was funded by Genentech, Inc. Support for third-party writing assistance was provided by Genentech, Inc. NR 24 TC 27 Z9 27 U1 0 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD OCT PY 2012 VL 70 IS 4 BP 591 EP 601 DI 10.1007/s00280-012-1934-7 PG 11 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 011YF UT WOS:000309201500013 PM 22886072 ER PT J AU Li, J Zeng, W Huang, Y Zhang, Q Hu, P Rabkin, SD Liu, R AF Li, J. Zeng, W. Huang, Y. Zhang, Q. Hu, P. Rabkin, S. D. Liu, R. TI Treatment of breast cancer stem cells with oncolytic herpes simplex virus SO CANCER GENE THERAPY LA English DT Article DE breast cancer; cancer stem cells; HSV; oncolytic virus ID SIDE POPULATION; PHASE-I; THERAPY; VECTOR; MUTANT; ASSOCIATION; FIBROBLASTS; EXPRESSION; RESISTANCE; TRIAL AB Cancer stem cells have recently been isolated from several different solid tumors. In breast cancer, the CD44(+)CD24(-/low) population is considered to comprise stem-like cells. The identification of cancer stem cells has provided new targets for the development of therapeutics. Oncolytic herpes simplex viruses (oHSVs) are an effective strategy for killing breast cancer cells and treating breast tumors in preclinical models. Here, we examined the efficacy of the oHSV G47 Delta in killing breast cancer stem cells. Human breast cancer cell line SK-BR-3 and human primary breast cancer cells were cultured in suspension under conditions conducive to the growth of stem cells. They generated mammospheres, which had cancer stem cell properties. The proportion of CD44(+)CD24(-/low) cells in these mammospheres exceeded 95%, as determined by flow cytometry. The mammospheres were found to be highly tumorigenic when implanted subcutaneously in nude BALB/c mice. G47 Delta contains the LacZ gene, and X-gal staining of infected cells in vitro and in vivo showed the replication and spread of the virus. G47 Delta was found to be highly cytotoxic to the CD44(+)CD24(-/low) population in vitro, even when injected at low multiplicities of infection, and G47 Delta treatment in vivo significantly inhibited tumor growth compared with mock treatment. This study demonstrates that oHSV is effective against breast cancer stem cells and could be a beneficial strategy for treating breast cancer patients. C1 [Li, J.; Zeng, W.; Huang, Y.; Hu, P.; Liu, R.] Sun Yat Sen Univ, Affiliated Hosp 3, Breast Canc Ctr, Guangzhou 510630, Guangdong, Peoples R China. [Li, J.] Sichuan Prov Canc Hosp, Dept Breast Surg, Chengdu, Peoples R China. [Zhang, Q.] Sun Yat Sen Univ, Affiliated Hosp 3, Cent Lab, Guangzhou 510630, Guangdong, Peoples R China. [Rabkin, S. D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurosurg Lab, Boston, MA USA. RP Liu, R (reprint author), Sun Yat Sen Univ, Affiliated Hosp 3, Breast Canc Ctr, Guangzhou 510630, Guangdong, Peoples R China. EM liur@vip.163.com NR 35 TC 11 Z9 12 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD OCT PY 2012 VL 19 IS 10 BP 707 EP 714 DI 10.1038/cgt.2012.49 PG 8 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 006UT UT WOS:000308845400006 PM 22898897 ER PT J AU Young, MR AF Young, M. Rita TI Endothelial cells in the eyes of an immunologist SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Review DE Endothelial cells; Cancer; Immunoregulation; Immune trafficking ID T-CELLS; VIRUS-INFECTION; EXPRESSION; ACTIVATION; SECRETION; IMMUNITY; PROLIFERATION; MACROPHAGES; RECRUITMENT; RESPONSES AB Endothelial cell activation in the process of tumor angiogenesis and in various aspects of vascular biology has been extensively studied. However, endothelial cells also function in other capacities, including in immune regulation. Compared to the more traditional immune regulatory populations (Th1, Th2, Treg, etc.), endothelial cells have received far less credit as being immune regulators. Their regulatory capacity is multifaceted. They are critical in both limiting and facilitating the trafficking of various immune cell populations, including T cells and dendritic cells, out of the vasculature and into tissue. They also can be induced to stimulate immune reactivity or to be immune inhibitory. In each of these parameters (trafficking, immune stimulation and immune inhibition), their role can be physiological, whereby they have an active role in maintaining health. Alternatively, their role can be pathological, whereby they contribute to disease. In theory, endothelial cells are in an ideal location to recruit cells that can mediate immune reactivity to tumor tissue. Furthermore, they can activate the immune cells as they transmigrate across the endothelium into the tumor. However, what is seen is the absence of these protective effects of endothelial cells and, instead, the endothelial cells succumb to the defense mechanisms of the tumor, resulting in their acquisition of a tumor-protective role. To understand the immune regulatory potential of endothelial cells in protecting the host versus the tumor, it is useful to better understand the other circumstances in which endothelial cells modulate immune reactivities. Which of the multitude of immune regulatory roles that endothelial cells can take on seems to rely on the type of stimulus that they are encountering. It also depends on the extent to which they can be manipulated by potential dangers to succumb and contribute toward attack on the host. This review will explore the physiological and pathological roles of endothelial cells as they regulate immune trafficking, immune stimulation and immune inhibition in a variety of conditions and will then apply this information to their role in the tumor environment. Strategies to harness the immune regulatory potential of endothelial cells are starting to emerge in the non-tumor setting. Results from such efforts are expected to be applicable to being able to skew endothelial cells from having a tumor-protective role to a host-protective role. C1 [Young, M. Rita] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29401 USA. [Young, M. Rita] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29401 USA. [Young, M. Rita] Med Univ S Carolina, Dept Med, Charleston, SC 29401 USA. RP Young, MR (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29401 USA. EM rita.young@va.gov FU Department of Veterans Affairs [CX000100]; National Institutes of Health [RO1 CA128837, RO1 DE018268] FX This work was supported by the Department of Veterans Affairs through a Clinical Sciences Research & Development award (CX000100) and a Senior Research Career Scientist award, and by grants RO1 CA128837 and RO1 DE018268 from the National Institutes of Health. NR 38 TC 5 Z9 5 U1 2 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 EI 1432-0851 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD OCT PY 2012 VL 61 IS 10 BP 1609 EP 1616 DI 10.1007/s00262-012-1335-0 PG 8 WC Oncology; Immunology SC Oncology; Immunology GA 010CO UT WOS:000309072300001 PM 22903347 ER PT J AU Ganguli, S Kalva, S Oklu, R Walker, TG Datta, N Grabowski, EF Wicky, S AF Ganguli, Suvranu Kalva, Sanjeeva Oklu, Rahmi Walker, T. Gregory Datta, Neil Grabowski, Eric F. Wicky, Stephan TI Efficacy of Lower-Extremity Venous Thrombolysis in the Setting of Congenital Absence or Atresia of the Inferior Vena Cava SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE Inferior vena cava atresia; Pharmacomechanical catheter-directed thrombolysis; Lower-extremity deep vein thrombosis; Postthrombotic syndrome ID DEEP-VEIN THROMBOSIS; POSTTHROMBOTIC SYNDROME; RISK-FACTOR; ENDOVASCULAR TREATMENT; INTERRUPTION; CHILDREN; CLASSIFICATION; POPULATION; ANOMALIES; SECONDARY AB A rare but described risk factor for deep venous thrombosis (DVT), predominately in the young, is congenital agenesis or atresia of the inferior vena cava (IVC). The optimal management for DVT in this subset of patients is unknown. We evaluated the efficacy of pharmacomechanical catheter-directed thrombolysis (PCDT) followed by systemic anticoagulation in the treatment of acute lower-extremity DVT in the setting of congenital IVC agenesis or atresia. Between November of 2005 and May of 2010, six patients (three women [average age 21 years]) were referred to our department with acute lower-extremity DVT and subsequently found to have IVC agenesis or atresia on magnetic resonance imaging. A standardized technique for PCDT (the Angiojet Rheolytic Thrombectomy System followed by the EKOS Microsonic Accelerated Thrombolysis System) was used for all subjects. Successful thrombolysis was followed by systemic heparinization with transition to Coumadin or low molecular-weight heparin and compression stockings. Subjects were followed-up at 1, 3, and then every 6 months after the procedure with clinical assessment and bilateral lower-extremity venous ultrasound. All PCDT procedures were technically successful. No venous stenting or angioplasty was performed. The average thrombolysis time was 28.6 h (range 12-72). Two patients experienced heparin-induced thrombocytopenia, and one patient developed a self-limited knee hemarthrosis, No patients were lost to follow-up. The average length of follow-up was 25.8 +/- A 20.2 months (range 3.8-54.8). No incidence of recurrent DVT was identified. There were no manifestations of postthrombotic syndrome. PCDT followed by systemic anticoagulation and the use of compression stockings appears to be safe and effective in relatively long-term follow-up treatment of patients who present with acute DVT and IVC agenesis or atresia. C1 [Ganguli, Suvranu; Kalva, Sanjeeva; Oklu, Rahmi; Walker, T. Gregory; Datta, Neil; Wicky, Stephan] Massachusetts Gen Hosp, Dept Imaging, Div Vasc Imaging & Intervent, Boston, MA 02114 USA. [Ganguli, Suvranu; Kalva, Sanjeeva; Oklu, Rahmi; Walker, T. Gregory; Datta, Neil; Grabowski, Eric F.; Wicky, Stephan] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Grabowski, Eric F.] Massachusetts Gen Hosp, Dept Pediat, Div Hematol & Oncol, Boston, MA 02114 USA. RP Ganguli, S (reprint author), Massachusetts Gen Hosp, Dept Imaging, Div Vasc Imaging & Intervent, 55 Fruit St,GRB 290, Boston, MA 02114 USA. EM sganguli@partners.org NR 24 TC 6 Z9 7 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0174-1551 J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD OCT PY 2012 VL 35 IS 5 BP 1053 EP 1058 DI 10.1007/s00270-011-0247-2 PG 6 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 008II UT WOS:000308950200011 PM 21847709 ER PT J AU d'Othee, BJ Walker, TG Waltman, AC Greenfield, AJ Koizumi, J AF d'Othee, Bertrand Janne Walker, T. Gregory Waltman, Arthur C. Greenfield, Alan J. Koizumi, Jun TI Reply to Letter Re: Management of Gastric Varices SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Letter C1 [d'Othee, Bertrand Janne] Univ Maryland, Sch Med, Dept Diagnost Radiol & Nucl Med, Div Vasc & Intervent Radiol, Baltimore, MD 21021 USA. [d'Othee, Bertrand Janne; Walker, T. Gregory; Waltman, Arthur C.; Greenfield, Alan J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Koizumi, Jun] Tokai Univ, Sch Med, Dept Diagnost Radiol, Tokyo 151, Japan. RP d'Othee, BJ (reprint author), Univ Maryland, Sch Med, Dept Diagnost Radiol & Nucl Med, Div Vasc & Intervent Radiol, 22 S Greene St, Baltimore, MD 21021 USA. EM bjannedothee@umm.edu; tgwalker@partners.org; awaltman@partners.org; agreenfield@partners.org; jkoizumi@is.icc.u-tokai.ac.jp RI Janne d'Othee, Bertrand/E-8467-2010 NR 2 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0174-1551 J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD OCT PY 2012 VL 35 IS 5 BP 1254 EP 1254 DI 10.1007/s00270-011-0251-6 PG 1 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 008II UT WOS:000308950200042 ER PT J AU Touchan, J Levy, MS Laham, RJ AF Touchan, Jean Levy, Michael S. Laham, Roger J. TI Percutaneous retrieval of fractured bird's nest IVC filter penetrating into aorta SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE complications adult cath; intervention; thrombosis; peripheral vascular disease ID VENA-CAVA FILTER AB Inferior vena cava filters can provide lifesaving protections in patients with recurrent venous thromboembolic disease that are not candidates for anticoagulation. They are, however, associated with short- and long-term complications necessitating frequent follow-up. The authors report, in this article, a case of migration of Bird's Nest filter strut into the descending aorta and its percutaneous retrieval by snaring and capture. This case also underscores the trend to use retrievable filters to avoid longer-term complications. (c) 2012 Wiley Periodicals, Inc. C1 [Touchan, Jean; Levy, Michael S.; Laham, Roger J.] Harvard Univ, Sch Med, BIDMC, Div Cardiol, Boston, MA 02215 USA. RP Laham, RJ (reprint author), Harvard Univ, Sch Med, BIDMC, Div Cardiol, 330 Brookline Ave, Boston, MA 02215 USA. EM rlaham@bidmc.harvard.edu NR 11 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD OCT 1 PY 2012 VL 80 IS 4 BP 657 EP 660 DI 10.1002/ccd.24304 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 008AN UT WOS:000308929600031 PM 22488685 ER PT J AU Manthripragada, G Schainfeld, R AF Manthripragada, Gopi Schainfeld, Robert TI An olympic challenge: Deconstructing a once useful "Bird's Nest" SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material ID VENA-CAVA FILTERS C1 Massachusetts Gen Hosp, Sect Vasc Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Schainfeld, R (reprint author), Massachusetts Gen Hosp, 52 2nd Ave,Suite 2100, Waltham, MA 02451 USA. EM rschainfeld@partners.org NR 5 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD OCT 1 PY 2012 VL 80 IS 4 BP 661 EP 662 DI 10.1002/ccd.24612 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 008AN UT WOS:000308929600032 PM 22996929 ER PT J AU Isvilanonda, V Dengler, E Iaquinto, JM Sangeorzan, BJ Ledoux, WR AF Isvilanonda, Vara Dengler, Evan Iaquinto, Joseph M. Sangeorzan, Bruce J. Ledoux, William R. TI Finite element analysis of the foot: Model validation and comparison between two common treatments of the clawed hallux deformity SO CLINICAL BIOMECHANICS LA English DT Article DE Modified Jones; FHL tendon transfer; Foot; Finite element analysis; Clawed hallux deformity ID MEDIAL LONGITUDINAL-ARCH; METATARSOPHALANGEAL JOINT; DIABETIC-PATIENTS; JONES PROCEDURE; TENDON TRANSFER; TOE DEFORMITY; PLANTAR; CARTILAGE; PRESSURE; FORCE AB Background: Clawed hallux is defined by first metatarsophalangeal joint extension and first interphalangeal joint flexion: it can increase plantar pressures and ulceration risk. We investigated two corrective surgical techniques, the modified Jones and flexor hallucis longus tendon transfer. Methods: A finite element foot model was modified to generate muscle overpulls, including extensor hallucis longus, flexor hallucis longus and peroneus longus. Both corrective procedures were simulated, predicting joint angle and plantar pressure changes. Findings: The clawed hallux deformity was generated by overpulling: 1) extensor hallucis longus, 2) peroneus longus + extensor hallucis longus, 3) extensor hallucis longus + flexor hallucis longus and 4) all three together. The modified Jones reduced metatarsophalangeal joint angles, but acceptable hallux pressure was found only when there was no flexor hallucis longus overpull. The flexor hallucis longus tendon transfer reduced deformity at the metatarsophalangeal and interphalangeal joints but may extended the hallux due to the unopposed extensor hallucis longus. Additionally, metatarsal head pressure increased with overpulling of the extensor hallucis longus + flexor hallucis longus, and all three muscles together. Interpretation: The modified Jones was effective in correcting clawed hallux deformity involving extensor hallucis longus overpull without flexor hallucis longus overpull. The flexor hallucis longus tendon transfer was effective in correcting clawed hallux deformity resulting from the combined overpull of both extensor and flexor hallucis longus, but not with isolated extensor hallucis longus overpull. An additional procedure to reduce the metatarsal head pressure may be required concomitant to the flexor hallucis longus tendon transfer. However this procedure avoids interphalangeal joint fusion. Published by Elsevier Ltd C1 [Isvilanonda, Vara; Dengler, Evan; Iaquinto, Joseph M.; Sangeorzan, Bruce J.; Ledoux, William R.] US Dept Vet Affairs, RR&D Ctr Excellence Limb Loss Prevent & Prosthet, Seattle, WA USA. [Isvilanonda, Vara; Dengler, Evan; Ledoux, William R.] Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. [Sangeorzan, Bruce J.; Ledoux, William R.] Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA. RP Ledoux, WR (reprint author), VA Puget Sound, Ms 151,1660 S Columbian Way, Seattle, WA 98108 USA. EM wrledoux@u.washington.edu RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714 FU VA Grants [A0806C, A2661C, A4843C, A6973R] FX This work is supported by the VA Grants A0806C, A2661C, A4843C and A6973R. The study sponsors played no role in the study design; in the collection, analysis and interpretation of data; in the writing of the manuscript: and in the decision to submit the manuscript for publication. The authors would also like to thank Daniel L A. Camacho and Joanna J. Blevins for their work on early versions of the foot model. NR 59 TC 16 Z9 16 U1 0 U2 25 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0268-0033 J9 CLIN BIOMECH JI Clin. Biomech. PD OCT PY 2012 VL 27 IS 8 BP 837 EP 844 DI 10.1016/j.clinbiomech.2012.05.005 PG 8 WC Engineering, Biomedical; Orthopedics; Sport Sciences SC Engineering; Orthopedics; Sport Sciences GA 006WP UT WOS:000308850800016 PM 22694884 ER PT J AU Kasckow, J Appelt, C Haas, GL Huegel, S Fox, L Gurklis, J Zickmund, S Daley, D AF Kasckow, J. Appelt, C. Haas, G. L. Huegel, S. Fox, L. Gurklis, J. Zickmund, S. Daley, D. TI Development of a Recovery Manual for Suicidal Patients with Schizophrenia: Consumer Feedback SO COMMUNITY MENTAL HEALTH JOURNAL LA English DT Article DE Schizophrenia; Suicide; Manual; Prevention; Recovery; Qualitative research ID HEALTH AB A recovery-oriented manual was developed for patients with schizophrenia and suicidality. It included psychoeducational information, vignettes, "workbook" sections and was reviewed by experts in suicidology, recovery, patient education, manual development and psychosocial interventions. The revised version was tested in 22 consumers with schizophrenia and a history of suicidality. Consumer-based focus groups yielded five key themes which were used to further refine the manual. A satisfaction survey indicated that 85% stated the manual was 'somewhat easy', 'easy' or 'very easy to read.' All stated it was 'very useful', 'useful' or 'somewhat useful. Thus, the manual appears to be acceptable and useful. C1 [Kasckow, J.; Haas, G. L.; Daley, D.] UPMC, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. [Kasckow, J.] VA Pittsburgh Hlth Care Syst MIRECC, Behav Hlth, Pittsburgh, PA 15206 USA. [Kasckow, J.; Zickmund, S.] Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Huegel, S.; Gurklis, J.] VA Pittsburgh Hlth Care Syst, Behav Hlth, Pittsburgh, PA 15206 USA. [Zickmund, S.] UPMC, Dept Med, Pittsburgh, PA 15213 USA. RP Kasckow, J (reprint author), UPMC, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. EM Kasckowjw@upmc.edu FU NIMH NIH HHS [T32 MH015169, T32 MH15169] NR 15 TC 0 Z9 0 U1 1 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0010-3853 J9 COMMUNITY MENT HLT J JI Community Ment. Health J. PD OCT PY 2012 VL 48 IS 5 BP 564 EP 567 DI 10.1007/s10597-011-9477-7 PG 4 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 013XK UT WOS:000309339200004 PM 22187086 ER PT J AU Malinoski, DJ Patel, MS Daly, MC Oley-Graybill, C Salim, A AF Malinoski, Darren J. Patel, Madhukar S. Daly, Michael C. Oley-Graybill, Chrystal Salim, Ali CA UNOS Region 5 DMG Workgrp TI The impact of meeting donor management goals on the number of organs transplanted per donor: Results from the United Network for Organ Sharing Region 5 prospective donor management goals study SO CRITICAL CARE MEDICINE LA English DT Article DE donor management goals; checklist; organ donation; critical care; catastrophic brain injury guidelines ID POTENTIAL HEART; BRAIN-DEATH; DONATION; RETRIEVAL; INCREASES; OUTCOMES; THERAPY; YIELDS AB Objective: Many organ procurement organizations have implemented critical care end points as donor management goals in efforts to increase organs transplanted per donor after neurologic determination of death. Although retrospective studies have demonstrated an association between meeting donor management goals and organ yield, prospective studies are lacking. Design: In June 2008, nine donor management goals were prospectively implemented as a checklist and every donor after neurologic determination of death was managed to meet them. The donor management goals represented normal cardiovascular, pulmonary, renal, and endocrine end points. Data were collected for 7 months. Donor management goals "met" was defined a priori as achieving any seven of the nine donor management goals, and this was recorded at the time of consent, 12-18 hrs later, and prior to organ recovery. The primary outcome measure was >= 4 organs transplanted per donor, and binary logistic regression was used to identify independent predictors of this outcome with a p < .05. Setting: All eight organ procurement organizations in the five Southwestern United States (United Network for Organ Sharing Region 5). Subjects: All standard criteria donors after neurologic determination of deaths. Intervention: Prospective implementation of a donor management goal checklist. Measurements and Main Results: There were 380 standard criteria donors with 3.6 +/- 1.7 organs transplanted per donor. Fifteen percent had donor management goals met at the time of consent, 33% at 12-18 hrs, and 38% prior to organ recovery. Forty-eight percent had >= 4 organs transplanted per donor. Donors with >= 4 organs transplanted per donor had significantly more individual donor management goals met at all three time points. Independent predictors of >= 4 organs transplanted per donor were age (odds ratio =0.95 per year), final creatinine (odds ratio = 0.75 per 1-unit increase), donor management goals "met" at consent (odds ratio = 2.03), donor management goals "met" prior to organ recovery (odds ratio = 2.34), and a change in the number of donor management goals achieved from consent to 12-18 hrs later (odds ratio = 1.13 per additional donor management goal). Conclusions: Meeting donor management goals prior to consent and prior to organ recovery were both associated with achieving = 4 organs transplanted per donor. However, only 15% of donors have donor management goals met at the time of consent. The donor hospital management of patients with catastrophic brain injuries, before the intent to donate organs is known, affects outcomes and should remain a priority in the intensive care unit. (Crit Care Med 2012; 40:2773-2780) C1 [Malinoski, Darren J.; Salim, Ali] Cedars Sinai Med Ctr, Dept Surg, Los Angeles, CA 90048 USA. [Daly, Michael C.] Univ Calif Irvine, Dept Surg, Orange, CA 92668 USA. [Patel, Madhukar S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Oley-Graybill, Chrystal] United Network Organ Sharing, Richmond, VA USA. RP Malinoski, DJ (reprint author), Portland VA Med Ctr, Sect Surg Crit Care, POB 1034,Mail Code P3ANES, Portland, OR 97207 USA. EM malinosk@ohsu.edu FU Health Resources and Services Administration [234-2005-37011C] FX Supported, in part, by Health Resources and Services Administration contract 234-2005-37011C. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. The authors have not disclosed any potential conflicts of interest. NR 24 TC 32 Z9 33 U1 2 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD OCT PY 2012 VL 40 IS 10 BP 2773 EP 2780 DI 10.1097/CCM.0b013e31825b252a PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 007XB UT WOS:000308920600005 PM 22846779 ER PT J AU Sloan, SR Steiner, ME Stowell, CP Assmann, SF Delaney, M Triulzi, D AF Sloan, Steven R. Steiner, Marie E. Stowell, Christopher P. Assmann, Susan F. Delaney, Meghan Triulzi, Darrell TI Current randomized clinical trials of red cell storage duration and patient outcomes SO CRITICAL CARE MEDICINE LA English DT Letter ID BLOOD-CELLS; DESIGN; FRESH; AGE C1 [Sloan, Steven R.] Childrens Hosp Boston, Boston, MA USA. [Sloan, Steven R.; Stowell, Christopher P.] Harvard Univ, Sch Med, Boston, MA USA. [Steiner, Marie E.] Univ Minnesota, Minneapolis, MN USA. [Stowell, Christopher P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Assmann, Susan F.] New England Res Inst, Watertown, MA 02172 USA. [Delaney, Meghan] Univ Washington, Seattle, WA 98195 USA. [Delaney, Meghan] Puget Sound Blood Ctr, Seattle, WA 98104 USA. [Triulzi, Darrell] Univ Pittsburgh, Pittsburgh, PA USA. RP Sloan, SR (reprint author), Childrens Hosp Boston, Boston, MA USA. NR 5 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD OCT PY 2012 VL 40 IS 10 BP 2927 EP 2927 DI 10.1097/CCM.0b013e31825f7aa3 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 007XB UT WOS:000308920600045 PM 22986676 ER PT J AU Merfeld, DM Lewis, RF AF Merfeld, Daniel M. Lewis, Richard F. TI Replacing semicircular canal function with a vestibular implant SO CURRENT OPINION IN OTOLARYNGOLOGY & HEAD AND NECK SURGERY LA English DT Review DE neural implant; neural prosthesis; prosthesis; sensory replacement; spatial orientation; VOR ID ELECTRICAL-STIMULATION; EYE-MOVEMENTS; PROSTHESIS; NERVE; ADAPTATION; RESPONSES; SYSTEM AB Purpose of review To summarize the recent progress in the development of vestibular implants. The review is timely because of the recent advances in the field and because MED-EL has recently announced that they are developing a vestibular implant for clinical applications. Recent findings The handicap experienced by patients suffering from bilateral vestibulopathy has a strong negative impact on physical and social functioning that appears to justify a surgical intervention. Two different surgical approaches to insert electrodes to stimulate ampullary neurons have been shown to be viable. The three-dimensional vestibulo-ocular reflex in rhesus monkeys produced with a three-dimensional vestibular implant showed gains that were relatively normal during acute stimulation. Rotation cues provided by an implant interact with otolith cues in a qualitatively normal manner. The brain appears to adapt plastically to the cues provided via artificial electrical stimulation. Summary Research to date includes just a few human studies, but available data from both humans and animals support the technological and physiological feasibility of vestibular implants. Although vestibular implant users should not expect normal vestibular function - any more than cochlear implant users should expect normal hearing - data suggest that significant functional improvements are possible. C1 [Merfeld, Daniel M.; Lewis, Richard F.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. [Merfeld, Daniel M.; Lewis, Richard F.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Lewis, Richard F.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. RP Merfeld, DM (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Jenks Vestibular Physiol Lab, MEEI Room 421,243 Charles St, Boston, MA 02114 USA. EM dan_merfeld@meei.harvard.edu FU NIH/NIDCD [DC-08362]; EU [225929, 'CLONS']; MED-EL; Massachusetts Eye and Ear Infirmary FX The authors receive salary support for vestibular implant research funded by the NIH/NIDCD (DC-08362), the EU (225929, 'CLONS'), and MED-EL via grants with the Massachusetts Eye and Ear Infirmary. NR 46 TC 18 Z9 18 U1 2 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9508 J9 CURR OPIN OTOLARYNGO JI Curr. Opin. Otolaryngol. Head Neck Surg. PD OCT PY 2012 VL 20 IS 5 BP 386 EP 392 DI 10.1097/MOO.0b013e328357630f PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 006PO UT WOS:000308831500008 PM 22886037 ER PT J AU Chang, SY Chen, YW Zhao, XP Chenier, I Tran, S Sauve, A Ingelfinger, JR Zhang, SL AF Chang, Shiao-Ying Chen, Yun-Wen Zhao, Xin-Ping Chenier, Isabelle Tran, Stella Sauve, Alexandre Ingelfinger, Julie R. Zhang, Shao-Ling TI Catalase Prevents Maternal Diabetes-Induced Perinatal Programming via the Nrf2-HO-1 Defense System SO DIABETES LA English DT Article ID URETERAL BUD MORPHOGENESIS; PROXIMAL TUBULAR CELLS; TRANSGENIC MICE; IMMUNOHISTOCHEMICAL LOCALIZATION; OXIDATIVE STRESS; EPITHELIAL-CELLS; ANGIOTENSIN-II; EXPRESSION; KIDNEY; PREGNANCY AB We investigated whether overexpression of catalase (CAT) in renal proximal tubular cells (RPTCs) could prevent the programming of hypertension and kidney disease in the offspring of dams with maternal diabetes. Male offspring of nondiabetic and diabetic dams from two transgenic (Tg) lines (Hoxb7-green fluorescent protein [GFP]-Tg [controls] and Hoxb7/CAT-GFP-Tg, which over-express CAT in RPTCs) were studied from the prenatal period into adulthood. Nephrogenesis, systolic blood pressure, renal hyper-filtration, kidney injury, and reactive oxygen species (ROS) generation were assessed. Gene expression of transforming growth factor-beta 1 (TGF-beta 1), nuclear factor erythroid 2p45-related factor-2 (Nrf2), and heme oxygenase-1 (HO-1) was tested in both in vitro and in vivo studies. Renal dysmorphogenesis was observed in offspring of Hoxb7-GFP-Tg dams with severe maternal diabetes; the affected male offspring displayed higher renal ROS generation and developed hypertension and renal hyperfiltration as well as renal injury with heightened TGF-beta 1 expression in adulthood. These changes were ameliorated in male offspring of diabetic Hoxb7/CAT-GFP-Tg dams via the Nrf2-HO-1 defense system. CAT promoted Nrf2 nuclear translocation and HO-1 gene expression, seen in both in vitro and in vivo studies. In conclusion, CAT overexpression in the RPTCs ameliorated maternal diabetes-induced perinatal programming, mediated, at least in part, by triggering the Nrf2-HO-1 defense system. Diabetes 61:2565-2574, 2012 C1 [Chang, Shiao-Ying; Chen, Yun-Wen; Zhao, Xin-Ping; Chenier, Isabelle; Tran, Stella; Sauve, Alexandre; Zhang, Shao-Ling] Univ Montreal, CRCHUM, Hop Hotel Dieu, Montreal, PQ, Canada. [Ingelfinger, Julie R.] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. [Ingelfinger, Julie R.] Harvard Univ, Sch Med, Boston, MA USA. RP Zhang, SL (reprint author), Univ Montreal, CRCHUM, Hop Hotel Dieu, Montreal, PQ, Canada. EM shao.ling.zhang@umontreal.ca FU Canadian Institutes of Health Research [MOP115025]; American Society of Nephrology; Bourse de Chercheure-Boursier Juniors 2-Fonds de Recherche en Sante du Quebec FX This project was supported by grants to S.-L.Z. from the Canadian Institutes of Health Research (MOP115025), the American Society of Nephrology (Carl W. Gottschalk Research Scholar), and the Bourse de Chercheure-Boursier Juniors 2-Fonds de Recherche en Sante du Quebec. NR 50 TC 13 Z9 13 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2012 VL 61 IS 10 BP 2565 EP 2574 DI 10.2337/db12-0248 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 013KP UT WOS:000309304600021 PM 22733796 ER PT J AU Lo, CS Chang, SY Chenier, I Filep, JG Ingelfinger, JR Zhang, SL Chan, JSD AF Lo, Chao-Sheng Chang, Shiao-Ying Chenier, Isabelle Filep, Janos G. Ingelfinger, Julie R. Zhang, Shao Ling Chan, John S. D. TI Heterogeneous Nuclear Ribonucleoprotein F Suppresses Angiotensinogen Gene Expression and Attenuates Hypertension and Kidney Injury in Diabetic Mice SO DIABETES LA English DT Article ID PROXIMAL TUBULAR CELLS; PROTEIN-KINASE PATHWAY; TRANSGENIC MICE; MESSENGER-RNA; HIGH GLUCOSE; HNRNP-F; BINDING PROTEIN; TRANSFORMING GROWTH-FACTOR-BETA-1; TRANSCRIPTION FACTOR; RESPONSIVE ELEMENT AB We investigated the impact of heterogeneous nuclear ribonucleoprotein F (hnRNP F) overexpression on angiotensinogen (Agt) gene expression, hypertension, and renal proximal tubular cell (RPTC) injury in high-glucose milieu both in vivo and in vitro. Diabetic Akita transgenic (Tg) mice specifically overexpressing hnRNP F in their RPTCs were created, and the effects on systemic hypertension, Agt gene expression, renal hypertrophy, and interstitial fibrosis were studied. We also examined immortalized rat RPTCs stably transfected with control plasmid or plasmid containing hnRNP F cDNA in vitro. The results showed that hnRNP F overexpression attenuated systemic hypertension, suppressed Agt and transforming growth factor-beta 1 (TGF-beta 1) gene expression, and reduced urinary Agt and angiotensin II levels, renal hypertrophy, and glomerulotubular fibrosis in Akita hnRNP F-Tg mice. In vitro, hnRNP F overexpression prevented the high-glucose stimulation of Agt and TGF-beta 1 mRNA expression and cellular hypertrophy in RPTCs. These data suggest that hnRNP F plays a modulatory role and can ameliorate hypertension, renal hypertrophy, and interstitial fibrosis in diabetes. The underlying mechanism is mediated, at least in part, via the suppression of intrarenal Agt gene expression in vivo. hnRNP F may be a potential target in the treatment of hypertension and kidney injury in diabetes. Diabetes 61:2597-2608, 2012 C1 [Lo, Chao-Sheng; Chang, Shiao-Ying; Chenier, Isabelle; Zhang, Shao Ling; Chan, John S. D.] Univ Montreal, Hop Hotel Dieu, Ctr Rech, Ctr Hosp Univ Montreal, Montreal, PQ, Canada. [Filep, Janos G.] Hop Maison Neuve Rosemont, Res Ctr, Montreal, PQ H1T 2M4, Canada. [Ingelfinger, Julie R.] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. RP Chan, JSD (reprint author), Univ Montreal, Hop Hotel Dieu, Ctr Rech, Ctr Hosp Univ Montreal, Montreal, PQ, Canada. EM john.chan@umontreal.ca FU Canadian Institutes of Health Research [MOP-84363, MOP-93650, MOP-16088, MOP-86450, MOP-64283]; Heart and Stroke Foundation of Canada; National Institutes of Health [HL-48455] FX This work was supported by grants from the Canadian Institutes of Health Research (MOP-84363, MOP-93650, and MOP-16088 to J.S.D.C., MOP-86450 to S.L.Z., and MOP-64283 to J.G.F.), the Heart and Stroke Foundation of Canada (to J.S.D.C.), and the National Institutes of Health (HL-48455 to J.R.I.). NR 43 TC 6 Z9 6 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2012 VL 61 IS 10 BP 2597 EP 2608 DI 10.2337/db11-1349 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 013KP UT WOS:000309304600025 PM 22664958 ER PT J AU Kaunitz, JD AF Kaunitz, Jonathan D. TI From Bedside to Bench: Reverse Engineering Medical Progress SO DIGESTIVE DISEASES AND SCIENCES LA English DT Editorial Material ID HISTAMINE C1 [Kaunitz, Jonathan D.] W Los Angeles VAMC, Los Angeles, CA 90073 USA. [Kaunitz, Jonathan D.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90073 USA. RP Kaunitz, JD (reprint author), W Los Angeles VAMC, Bldg 114,Room 217E, Los Angeles, CA 90073 USA. EM jdkaunitz@gmail.com FU BLRD VA [I01 BX001245]; NIDDK NIH HHS [R01 DK054221] NR 8 TC 0 Z9 0 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD OCT PY 2012 VL 57 IS 10 BP 2481 EP 2483 DI 10.1007/s10620-012-2386-y PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 012HQ UT WOS:000309227300001 PM 22983560 ER PT J AU Welters, HJ El Ouaamari, A Kawamori, D Meyer, J Hu, J Smith, DM Kulkarni, RN AF Welters, Hannah J. El Ouaamari, Abdelfattah Kawamori, Dan Meyer, John Hu, Jiang Smith, David M. Kulkarni, Rohit N. TI Rosiglitazone Promotes PPAR gamma-Dependent and -Independent Alterations in Gene Expression in Mouse Islets SO ENDOCRINOLOGY LA English DT Article ID ACTIVATED-RECEPTOR-GAMMA; PANCREATIC BETA-CELLS; STIMULATED INSULIN-SECRETION; IN-VIVO; GLUCOSE-HOMEOSTASIS; RESPONSE ELEMENT; DIABETIC MICE; PIOGLITAZONE; MASS; RAT AB The glitazone class of insulin-sensitizing agents act, in part, by the activation of peroxisome proliferator-activated receptor (PPAR)-gamma in adipocytes. However, it is unclear whether the expression of PPAR gamma in the islets is essential for their potential beta-cell-sparing properties. To investigate the in vivo effects of rosiglitazone on beta-cell biology, we used an inducible, pancreatic and duodenal homeobox-1 enhancer element-driven, Cre recombinase to knockout PPAR gamma expression specifically in adult beta-cells (PPARgKO). Subjecting the PPARgKO mice to a chow diet led to virtually undetectable changes in glucose or insulin sensitivity, which was paralleled by minimal changes in islet gene expression. Similarly, challenging the mutant mice with a high-fat diet and treatment with rosiglitazone did not alter insulin sensitivity, glucose-stimulated insulin secretion, islet size, or proliferation in the knockout mice despite PPAR gamma-dependent and -independent changes in islet gene expression. These data suggest that PPAR gamma expression in the beta-cells is unlikely to be directly essential for normal beta-cell function or the insulin-sensitizing actions of rosiglitazone. (Endocrinology 153: 4593-4599, 2012) C1 [Welters, Hannah J.; El Ouaamari, Abdelfattah; Kawamori, Dan; Meyer, John; Hu, Jiang; Kulkarni, Rohit N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Cell Biol & Regenerat Med, Boston, MA 02115 USA. [Smith, David M.] AstraZeneca, Cardiovasc & Gastrointestinal Innovat Med, Macclesfield SK10 4TG, Cheshire, England. [Welters, Hannah J.] Univ Exeter, Peninsula Coll Med & Dent, Inst Biomed & Clin Sci, Exeter EX1 2LU, Devon, England. [Kawamori, Dan] Osaka Univ, Grad Sch Med, Med Educ Ctr, Suita, Osaka 5650871, Japan. [Kawamori, Dan] Osaka Univ, Grad Sch Med, Dept Metab Med, Suita, Osaka 5650871, Japan. RP Welters, HJ (reprint author), Univ Exeter, Peninsula Coll Med & Dent, Exeter EX2 5DW, Devon, England. EM hannah.welters@pcmd.ac.uk FU National Institutes of Health [RO1 DK67536]; AstraZeneca FX This work was supported by National Institutes of Health Grant RO1 DK67536 and a grant from AstraZeneca. NR 36 TC 11 Z9 12 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 2012 VL 153 IS 10 BP 4593 EP 4599 DI 10.1210/en.2012-1243 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 012BK UT WOS:000309210200001 PM 22807489 ER PT J AU Monk, BJ Herzog, TJ Kaye, SB Krasner, CN Vermorken, JB Muggia, FM Pujade-Lauraine, E Park, YC Parekh, TV Poveda, AM AF Monk, Bradley J. Herzog, Thomas J. Kaye, Stanley B. Krasner, Carolyn N. Vermorken, Jan B. Muggia, Franco M. Pujade-Lauraine, Eric Park, Youn C. Parekh, Trilok V. Poveda, Andres M. TI Trabectedin plus pegylated liposomal doxorubicin (PLD) versus PLD in recurrent ovarian cancer: Overall survival analysis SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE Trabectedin; Pegylated liposomal doxorubicin; Recurrent ovarian cancer ID LONG-TERM SURVIVAL; PHASE-III; STAGE-III; PACLITAXEL; CARCINOMA; CISPLATIN; CARBOPLATIN; TOPOTECAN; TRIAL; CHEMOTHERAPY AB Aim: Trabectedin in combination with pegylated liposomal doxorubicin (PLD) improves progression-free survival (PFS) compared to PLD alone in recurrent ovarian cancer (J Clin Oncol 2010; 28: 3107-14). Methods: Women, stratified by performance status (0-1 versus 2) and platinum sensitivity (platinum-free interval [PFI] < 6 versus >= 6 months), were randomly assigned to receive PLD 30 mg/m(2) IV followed by a 3-h infusion of trabectedin 1.1 mg/m(2) every 3 weeks or PLD 50 mg/m(2) every 4 weeks. The study was powered to show a 33% increase in overall survival (OS) after 520 deaths had occurred. Results: After a median follow-up of 47.4 months, there were 522 deaths among 672 subjects. The median OS for trabectedin + PLD and PLD arms was 22.2 and 18.9 months, respectively (hazard ratio [HR] = 0.86; 95% confidence interval [CI]: 0.72-1.02; p = 0.0835). An unexpected but significant imbalance in the PFI favouring the PLD arm (mean PFI: PLD = 13.3 months, trabectedin + PLD = 10.6 months) was identified. On the basis of this finding, an unplanned hypothesis generating analysis adjusting for the PFI imbalance and other prognostic factors suggested an improvement in OS associated with the trabectedin + PLD arm (HR = 0.82; 95% CI: 0.69-0.98; p = 0.0285). In another unplanned exploratory analysis, the subset of patients with a PFI of 6-12 months had the largest difference in OS (HR = 0.64; 95% CI: 0.47-0.86; p = 0.0027). Conclusions: The final OS analysis did not meet the protocol-defined criterion for statistical significance. Despite stratification on platinum sensitivity, there was an imbalance in mean platinum free interval that had an effect on OS. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Monk, Bradley J.] Creighton Univ, St Josephs Hosp & Med Ctr, Sch Med, Div Gynecol Oncol,Dept Obstet & Gynecol, Phoenix, AZ 85013 USA. [Herzog, Thomas J.] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Kaye, Stanley B.] Royal Marsden Hosp, Surrey, England. [Krasner, Carolyn N.] Massachusetts Gen Hosp, Gillette Ctr Womens Studies, Boston, MA 02114 USA. [Vermorken, Jan B.] Univ Antwerp Hosp, Edegem, Belgium. [Muggia, Franco M.] NYU, Langone Med Ctr, New York, NY USA. [Pujade-Lauraine, Eric] Univ Paris 05, Hop Univ Paris Ctr Site Hotel Dieu, APHP, Paris, France. [Park, Youn C.; Parekh, Trilok V.] Johnson & Johnson Pharmaceut Res & Dev LLC, Raritan, NJ USA. [Poveda, Andres M.] Inst Valenciano Oncol, Valencia, Spain. RP Monk, BJ (reprint author), Creighton Univ, St Josephs Hosp & Med Ctr, Sch Med, Div Gynecol Oncol,Dept Obstet & Gynecol, 500 W Thomas Rd,Suite 600, Phoenix, AZ 85013 USA. EM Bradley.Monk@chw.edu OI Muggia, Franco/0000-0003-0703-9146 FU Johnson & Johnson Pharmaceutical Research & Development, L.L.C.; PharmaMar, S.A. FX Johnson & Johnson Pharmaceutical Research & Development, L.L.C. and PharmaMar, S.A. funded the clinical trial and provided the investigational product. NR 25 TC 28 Z9 28 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD OCT PY 2012 VL 48 IS 15 BP 2361 EP 2368 DI 10.1016/j.ejca.2012.04.001 PG 8 WC Oncology SC Oncology GA 012VT UT WOS:000309265400009 PM 22541893 ER PT J AU Lim, K Merfeld, DM AF Lim, Koeun Merfeld, Daniel M. TI Signal detection theory and vestibular perception: II. Fitting perceptual thresholds as a function of frequency SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE Detection theory; Vestibular perception; Threshold; Psychophysics; Generalized linear model ID QUALITATIVELY DIFFERENT MECHANISMS; INNERVATING SEMICIRCULAR CANALS; SELF-MOTION PERCEPTION; EARTH-VERTICAL AXIS; VELOCITY STORAGE; PSYCHOMETRIC FUNCTIONS; SQUIRREL MONKEY; WHOLE-BODY; VOR; TRANSLATION AB Vestibular perceptual thresholds are defined by a dynamic sensory system. To capture these dynamics, thresholds were previously fit as a function of frequency. In this paper, we compare fits using two published models with two new models. Furthermore, a new fitting method that utilizes vestibular perceptual dynamics is developed to improve fit quality and overcome problems associated with the conventional approach. Combinations of the four models and two fitting methods are tested using both simulated data and previously published experimental data. Simulations reveal that the conventional approach underestimates thresholds when the number of trials at each frequency is limited (circa 50); this underestimation is reduced fivefold by the new fitting method that simultaneously utilizes data across frequencies. The new fitting method also scored best for goodness of fit for both the simulations and experimental data. In fact, the new approach of fitting simultaneously across frequencies proved more accurate, more precise, more robust, and more efficient than the conventional approach of fitting the responses at each frequency individually and then fitting these threshold data across frequency. The revised fit of published yaw rotation threshold data shows that these are best fit by a first-order high-pass filter having a plateau of 0.5A degrees/s (roughly a factor of 4 higher than the motion platform vibration) at frequencies above the cutoff frequency of 0.26 Hz, which is well above the cutoff frequency of the semicircular canals (circa 0.03 Hz). This dynamic analysis suggests the contributions of a velocity leakage mechanism to human yaw rotation thresholds. C1 [Lim, Koeun; Merfeld, Daniel M.] Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. [Merfeld, Daniel M.] Harvard Univ, Sch Med, Boston, MA USA. RP Merfeld, DM (reprint author), Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, 243 Charles S,Suite 421, Boston, MA 02114 USA. EM koeunlim@mit.edu; dan_merfeld@meei.harvard.edu FU NIDCD NIH HHS [R01 DC004158] NR 43 TC 5 Z9 5 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD OCT PY 2012 VL 222 IS 3 BP 303 EP 320 DI 10.1007/s00221-012-3217-2 PG 18 WC Neurosciences SC Neurosciences & Neurology GA 010DE UT WOS:000309073900012 PM 22923225 ER PT J AU Campbell, EJ Krishnaraj, A Harris, M Saini, S Richter, JM AF Campbell, Emily J. Krishnaraj, Arun Harris, Mitchell Saini, Sanjay Richter, James M. TI Automated before-procedure electronic health record screening to assess appropriateness for GI endoscopy and sedation SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID COLORECTAL PROCEDURES; AGING POPULATION; OPEN-ACCESS; INFORMATION; MEANINGFUL; DEMAND; SEARCH; IMPACT AB Background: Endoscopists are performing greater numbers of procedures, often on patients with complex conditions, in ambulatory settings because of changing patient demographics and referral patterns. To assist with the pre-procedure assessment of such patients, we deployed an advanced electronic health record tool, the Queriable Patient Inference Dossier (QPID), to review clinical histories and generate e-mail alerts to providers, based on clinical guidelines. Objective: Study the feasibility of an automated pre-procedure alert system for outpatient endoscopy. Design: We retrospectively reviewed 5 physicians' use of the application and their responses to the alerts. Setting: A hospital-based endoscopy unit and its two satellite outpatient clinics, Boston area, Massachusetts. Patients: Adult outpatients referred for endoscopy with moderate sedation. Intervention: Pre-procedure alerts automatically sent 7 days before the procedure, highlighting any conditions/clinical history that may affect management of the patient. Main Outcome Measurements: Physician use of the pre-procedure alert system and its effect on patient management. Results: We studied 1682 procedures that met inclusion criteria for review by QPID and 364 alerts (1.6% of the eligible procedures). Nearly 80% of the alerts were reviewed and responded to by the physicians, and 70 total alerts resulted in a change in patient management (4.2% of eligible procedures). Limitations: The small size of the study group and the low rate of adverse events during the study period limit our findings. We thus plan to conduct a larger follow-up study to demonstrate changes in safety and efficiency. Conclusion: Use of advanced electronic health record technologies, such as QPID, may improve provider efficiency and patient outcomes in endoscopy units. (Gastrointest Endosc 2012;76:786-92.) C1 [Campbell, Emily J.; Richter, James M.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. [Krishnaraj, Arun; Harris, Mitchell; Saini, Sanjay] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Richter, JM (reprint author), Massachusetts Gen Hosp, Dept Gastroenterol, Blake 4, Boston, MA 02114 USA. EM jrichter@partners.org NR 27 TC 5 Z9 5 U1 1 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD OCT PY 2012 VL 76 IS 4 BP 786 EP 792 DI 10.1016/j.gie.2012.06.003 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 010QB UT WOS:000309108100013 PM 22901989 ER PT J AU Graetz, I Reed, M Fung, V Dow, WH Newhouse, JP Hsu, J AF Graetz, Ilana Reed, Mary Fung, Vicki Dow, William H. Newhouse, Joseph P. Hsu, John TI COBRA ARRA Subsidies: Was the Carrot Enticing Enough? SO HEALTH SERVICES RESEARCH LA English DT Article DE Premium subsidy; COBRA; individual mandate; care access ID ACUTE MYOCARDIAL-INFARCTION; HEALTH-CARE; UNINSURED ADULTS; INSURANCE-COVERAGE; INDIVIDUAL MANDATE; KNOWLEDGE; BENEFITS; REFORM; NEEDS AB Objective To help preserve continuity of health insurance coverage during the recent recession, the American Recovery and Reinvestment Act provided a 65 percent Consolidated Omnibus Budget Reconciliation Act (COBRA) premium subsidy for workers laid off in 20082010. We examined COBRA enrollment levels with the subsidy and the health, access, and financial consequences of enrollment decisions. Study Design/Data Collection Telephone interviews linked with health system databases for 561 respondents who were laid off in 2009 and eligible for the COBRA subsidy (80 percent response rate). Principal Findings Overall, 38 percent reported enrolling in COBRA and 54 percent reported having some gaps in insurance coverage since being laid off. After adjustments, we found that those who had higher cost-sharing, who had higher incomes, were older, or were sicker were more likely to enroll in COBRA. COBRA enrollees less frequently reported access problems or that their health suffered because of poor access, but they reported greater financial stress due to health care spending. Conclusion Despite the substantial subsidy, a majority of eligible individuals did not enroll in COBRA, and many reported insurance coverage gaps. Nonenrollees reported more access problems and that their health worsened. Without a mandate, subsidies may need to be widely publicized and larger to encourage health insurance enrollment among individuals who suffer a negative income shock. C1 [Graetz, Ilana; Reed, Mary] Kaiser Permanente, Div Res, Oakland, CA 94612 USA. [Graetz, Ilana; Dow, William H.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Fung, Vicki] Mid Atlantic Permanente Res Inst, Mid Atlantic Permanente Med Grp, Rockville, MD USA. [Newhouse, Joseph P.; Hsu, John] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Newhouse, Joseph P.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Newhouse, Joseph P.] Harvard Univ, Kennedy Sch, Boston, MA 02115 USA. [Hsu, John] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. RP Reed, M (reprint author), Kaiser Permanente, Div Res, 2000 Broadway,3rd Floor, Oakland, CA 94612 USA. EM mary.e.reed@kp.org RI Graetz, Ilana/N-1189-2016; OI Graetz, Ilana/0000-0003-3664-5815; Dow, William/0000-0002-4080-1668 FU Kaiser Foundation Research Institute FX This research was supported by Kaiser Foundation Research Institute. Newhouse is a director of and holds equity in Aetna, which sells COBRA eligible health plans. NR 35 TC 1 Z9 1 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD OCT PY 2012 VL 47 IS 5 BP 1980 EP 1998 DI 10.1111/j.1475-6773.2012.01409.x PG 19 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 008PR UT WOS:000308969500012 PM 22515835 ER PT J AU Tian, JW Hou, JB Xing, L Kim, SJ Yonetsu, T Kato, K Lee, H Zhang, SS Yu, B Jang, IK AF Tian, Jinwei Hou, Jingbo Xing, Lei Kim, Soo-Joong Yonetsu, Taishi Kato, Koji Lee, Hang Zhang, Shaosong Yu, Bo Jang, Ik-Kyung TI Significance of intraplaque neovascularisation for vulnerability: optical coherence tomography study SO HEART LA English DT Article ID CORONARY ATHEROSCLEROTIC PLAQUES; CAROTID PLAQUE; INTRAVASCULAR ULTRASOUND; CARDIOVASCULAR-DISEASE; ANGIOGENESIS; PROGRESSION; MICROVESSELS; INFLAMMATION; HEMORRHAGE; SYMPTOMS AB Objectives This study aimed to investigate the role of intraplaque neovascularisation (NV) in culprit lesions and non-culprit lesions of unstable angina pectoris (UAP) and in lesions of stable angina pectoris (SAP) using optical coherence tomography (OCT). Design This study was a retrospective study. Setting The significance of NV for culprit and non-culprit plaques remains unclear. Participants A total of 356 plaques from 92 UAP patients and 25 SAP patients who underwent OCT imaging were divided into three groups: culprit lesions in UAP (92), non-culprit lesions in UAP (203) and lesions of SAP (61). Main outcome measures NV and plaque characteristics were examined by OCT and plaques with and without NV were compared. Results Among UAP culprit lesions, plaques with NV had significantly higher incidence of thin cap fibroatheroma (81% vs 47%, p=0.002) compared with those without NV. In addition, the fibrous cap was thinner (56 +/- 20 mu m vs 75 +/- 30 mu m, p<0.001), lipid arc was greater (254 +/- 66 degrees vs 222 +/- 65 degrees, p=0.024) and lipid core length was longer (13 +/- 5 mm vs 10 +/- 6 mm, p=0.007). No significant difference was observed between non-culprit lesions of UAP with and without NV, and between lesions of SAP with and without NV. Conclusion In patients with UAP, the culprit plaques with NV had vulnerable features such as thinner fibrous cap, greater lipid arc, longer lipid core length and more frequent thin cap fibroatheroma compared with those without NV. In both non-culprit lesions of UAP patients and in lesions of SAP patients NV was not associated with vulnerable plaque characteristics. C1 [Tian, Jinwei; Hou, Jingbo; Xing, Lei; Yu, Bo] Harbin Med Univ, Affiliated Hosp 2, Minist Myocardial Ischemia Mechanism & Treatment, Dept Cardiol,Key Labs Educ, Harbin 150086, Peoples R China. [Kim, Soo-Joong; Yonetsu, Taishi; Kato, Koji; Jang, Ik-Kyung] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Lee, Hang] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA USA. [Zhang, Shaosong] St Jude Med, Clin Affairs, LightLab Imaging, Westford, MA USA. RP Yu, B (reprint author), Harbin Med Univ, Affiliated Hosp 2, Minist Myocardial Ischemia Mechanism & Treatment, Dept Cardiol,Key Labs Educ, Harbin 150086, Peoples R China. EM yubodr@163.com FU National Natural Science Foundation of China [81171430/H1816]; Science and Technology Key Project of Heilongjiang Province, China [GC10C305-3]; LightLab Imaging/St. Jude Medical FX This study was supported by grant 81171430/H1816 from the National Natural Science Foundation of China, and grant GC10C305-3 from the Science and Technology Key Project of Heilongjiang Province, China.; SZ is an employee of LightLab Imaging/St. Jude Medical. IKJ received a research grant for the MGH Registry from LightLab Imaging/St. Jude Medical. JT, BY, JH, LX, SJK, TY, KK and HL report no conflicts. NR 30 TC 20 Z9 23 U1 0 U2 5 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD OCT PY 2012 VL 98 IS 20 BP 1504 EP 1509 DI 10.1136/heartjnl-2012-302445 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 010TI UT WOS:000309116600008 PM 22869676 ER PT J AU Sinner, MF Porthan, K Noseworthy, PA Havulinna, AS Tikkanen, JT Muller-Nurasyid, M Peloso, G Ulivi, S Beckmann, BM Brockhaus, AC Cooper, RR Gasparini, P Hengstenberg, C Hwang, SJ Iorio, A Junttila, MJ Klopp, N Kahonen, M Laaksonen, MA Lehtimaki, T Lichtner, P Lyytikainen, LP Martens, E Meisinger, C Meitinger, T Merchant, FM Nieminen, MS Peters, A Pietila, A Perz, S Oikarinen, L Raitakari, O Reinhard, W Silander, K Thorand, B Wichmann, HE Sinagra, G Viikari, J O'Donnell, CJ Ellinor, PT Huikuri, HV Kaab, S Newton-Cheh, C Salomaa, V AF Sinner, Moritz F. Porthan, Kimmo Noseworthy, Peter A. Havulinna, Aki S. Tikkanen, Jani T. Mueller-Nurasyid, Martina Peloso, Gina Ulivi, Sheila Beckmann, Britt Maria Brockhaus, A. Catharina Cooper, Rebecca R. Gasparini, Paolo Hengstenberg, Christian Hwang, Shih-Jen Iorio, Annamaria Junttila, M. Juhani Klopp, Norman Kahonen, Mika Laaksonen, Maarit A. Lehtimaki, Terho Lichtner, Peter Lyytikainen, Leo-Pekka Martens, Eimo Meisinger, Christa Meitinger, Thomas Merchant, Faisal M. Nieminen, Markku S. Peters, Annette Pietila, Arto Perz, Siegfried Oikarinen, Lasse Raitakari, Olli Reinhard, Wibke Silander, Kaisa Thorand, Barbara Wichmann, H. -Erich Sinagra, Gianfranco Viikari, Jorma O'Donnell, Christopher J. Ellinor, Patrick T. Huikuri, Heikki V. Kaeaeb, Stefan Newton-Cheh, Christopher Salomaa, Veikko TI A meta-analysis of genome-wide association studies of the electrocardiographic early repolarization pattern SO HEART RHYTHM LA English DT Article DE Early repolarization; Sudden cardiac death; Arrhythmia; GWAS; Meta-analysis; Electrocardiogram ID TRANSIENT OUTWARD CURRENT; QT INTERVAL DURATION; J-POINT ELEVATION; J-WAVE SYNDROMES; ATRIAL-FIBRILLATION; COMMON VARIANTS; VENTRICULAR-FIBRILLATION; CHANNEL; KV4.3; MUTATIONS AB BACKGROUND The early repolarization pattern (ERP) is common and associated with risk of sudden cardiac death. ERP is heritable, and mutations have been described in syndromatic cases. OBJECTIVE To conduct a meta-analysis of genome-wide association studies to identify common genetic variants influencing ERP. METHODS We ascertained ERP on the basis of electrocardiograms in 3 large community-based cohorts from Europe and the United States: the Framingham Heart Study, the Health 2000 Study, and the KORA F4 Study. We analyzed genome-wide association studies in participants with and without ERP by logistic regression assuming an additive genetic model and meta-analyzed individual cohort results. We then sought to strengthen support for findings that reached P <= 1 x 10(-5) in independent individuals by direct genotyping or in-silico analysis of genome-wide data. We meta-analyzed the results from both stages. RESULTS Of 7482 individuals in the discovery stage, 452 showed ERP (ERP positive: mean age 46.9 +/- 8.9 years, 30.3% women; ERP negative: 47.5 +/- 9.4 years, 54.2% women). After meta-analysis, 8 single nucleotide polymorphisms reached P <= 1 x 10(-5): The most significant finding was intergenic rs11653989 (odds ratio 0.47; 95% confidence interval 0.36-0.61; P = 6.9 x 10(-9)). The most biologically relevant finding was intronic to KCND3: rs17029069 (odds ratio 1.46; 95% confidence interval 1.25-1.69; P = 8.5 x 10(-7)). In the replication step (7151 individuals), none of the 8 variants replicated, and combined meta-analysis results failed to reach genome-wide significance. CONCLUSIONS In a genome-wide association study, we were not able to reliably identify genetic variants predisposing to ERP, presumably due to insufficient statistical power and phenotype heterogeneity. The reported heritability of ERP warrants continued investigation in larger well-phenotyped populations. C1 [Sinner, Moritz F.; Noseworthy, Peter A.; Cooper, Rebecca R.; Merchant, Faisal M.; Ellinor, Patrick T.; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. [Peloso, Gina; Ellinor, Patrick T.; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Charlestown, MA USA. [Sinner, Moritz F.; Noseworthy, Peter A.; Peloso, Gina; Hwang, Shih-Jen; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Sinner, Moritz F.; Noseworthy, Peter A.; Peloso, Gina; Hwang, Shih-Jen; O'Donnell, Christopher J.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Sinner, Moritz F.; Mueller-Nurasyid, Martina; Beckmann, Britt Maria; Brockhaus, A. Catharina; Martens, Eimo; Kaeaeb, Stefan] Univ Munich, Dept Med 1, Univ Hosp Grosshadern, Munich, Germany. [Porthan, Kimmo; Nieminen, Markku S.; Oikarinen, Lasse] Univ Helsinki, Cent Hosp, Div Cardiol, Dept Med, Helsinki, Finland. [Havulinna, Aki S.; Pietila, Arto; Silander, Kaisa; Salomaa, Veikko] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Laaksonen, Maarit A.] Natl Inst Hlth & Welf, Dept Hlth Funct Capac & Welf, Helsinki, Finland. [Tikkanen, Jani T.; Junttila, M. Juhani; Huikuri, Heikki V.] Univ Oulu, Dept Internal Med, Inst Clin Med, SF-90220 Oulu, Finland. [Mueller-Nurasyid, Martina; Brockhaus, A. Catharina] German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany. [Klopp, Norman] German Res Ctr Environm Hlth, Inst Mol Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany. [Meisinger, Christa; Wichmann, H. -Erich] German Res Ctr Environm Hlth, Inst Epidemiol 1, Helmholtz Zentrum Munchen, Neuherberg, Germany. [Peters, Annette; Thorand, Barbara] German Res Ctr Environm Hlth, Inst Epidemiol 2, Helmholtz Zentrum Munchen, Neuherberg, Germany. [Perz, Siegfried] German Res Ctr Environm Hlth, Inst Biol & Med Imaging, Helmholtz Zentrum Munchen, Neuherberg, Germany. [Mueller-Nurasyid, Martina; Wichmann, H. -Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Epidemiol, Munich, Germany. [Mueller-Nurasyid, Martina] Univ Munich, Chair Genet Epidemiol, Munich, Germany. [Kahonen, Mika] Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland. [Kahonen, Mika] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland. [Lehtimaki, Terho; Lyytikainen, Leo-Pekka] Univ Tampere, Dept Clin Chem, Fimlab Ltd, FIN-33101 Tampere, Finland. [Ulivi, Sheila; Gasparini, Paolo] IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy. [Hengstenberg, Christian; Reinhard, Wibke] Univ Klinikum Regensburg, Klin & Poliklin Innere Med 2, Regensburg, Germany. [Lichtner, Peter; Meitinger, Thomas] German Res Ctr Environm Hlth, Inst Human Genet, Helmholtz Zentrum Munchen, Neuherberg, Germany. [Meitinger, Thomas; Peters, Annette; Kaeaeb, Stefan] Munich Heart Alliance, Munich, Germany. [Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol, FIN-20520 Turku, Finland. [Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. [Silander, Kaisa] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland. [Wichmann, H. -Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany. [Viikari, Jorma] Turku Univ Hosp, Dept Med, FIN-20520 Turku, Finland. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Ctr Human Genet Res, Cardiovasc Res Ctr, Div Cardiol, Boston, MA 02114 USA. [Iorio, Annamaria; Sinagra, Gianfranco] Azienda Osped Univ Univ Trieste, Cardiovasc Dept, Trieste, Italy. [Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. RP Newton-Cheh, C (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Cardiovasc Res Ctr, Div Cardiol, 185 Cambridge St,CPZN 5-242, Boston, MA 02114 USA. EM cnewtoncheh@partners.org RI Kaab, Stefan/H-3915-2012; Ulivi, Sheila/H-3700-2013; Meisinger, Christine/B-5358-2014; Thorand, Barbara/B-5349-2014; Meitinger, Thomas/O-1318-2015; Peters, Annette/A-6117-2011; Lyytikainen, Leo-Pekka/C-8544-2016; OI Ulivi, Sheila/0000-0003-3606-835X; Thorand, Barbara/0000-0002-8416-6440; Lyytikainen, Leo-Pekka/0000-0002-7200-5455; Meisinger, Christa/0000-0002-9026-6544; SINAGRA, GIANFRANCO/0000-0003-2700-8478 FU German Heart Foundation; Finnish Foundation for Cardiovascular Research; Orion-Farmos Research Foundation; Max Schaldach Fellowship in Cardiac Pacing and Electrophysiology; National Institutes of Health [RO1HL092577, 5R21DA027021, 1RO1HL104156, 1K24HL10578]; German National Genome Research Network NGFN-Plus [01GS0838]; German Federal Ministry for Education and Research (BMBF)/French Agence National de la Recherche (ANR) [SCD-Gene: 01KU0907]; BMBF cluster of excellence "personalized medicine M4"; National Institutes of Health; Burroughs Wellcome Fund; Academy of Finland [129494, 139635, 134309, 126925, 121584, 124282, 129378, 117787, 41071]; Affymetrix, Inc [N02-HL-6-4278]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine; Boston Medical Center; NHLBI Division of Intramural Research; National Institute for Health and Welfare; Finnish Centre for Pensions; Social Insurance Institution of Finland; Local Government Pensions Institution; Wellcome Trust Sanger Institute; BMBF; state of Bavaria; BMBF in the context of NGFN plus [01GS0838]; LMU Excellence Initiative; Munich Center of Health Sciences (MC Health) as part of LMUinnovativ; Social Insurance Institution of Finland, Kuopio, Tampere; Turku University Hospital Medical Funds [9M048, 9N035]; Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation of Cardiovascular Research; Finnish Cultural Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; project of "Genetic Park of FVG"; Regione FVG [L.26.2008]; Associazione Amici del Cuore FX This study was supported by the German Heart Foundation (to Dr Sinner), the Finnish Foundation for Cardiovascular Research (to Dr Porthan and Dr Oikarinen), the Orion-Farmos Research Foundation (to Dr Porthan), the Max Schaldach Fellowship in Cardiac Pacing and Electrophysiology (to Dr Noseworthy), National Institutes of Health grants RO1HL092577, 5R21DA027021, 1RO1HL104156, and 1K24HL10578 (to Dr Ellinor), the German National Genome Research Network NGFN-Plus (01GS0838) (to Dr Kaab), the German Federal Ministry for Education and Research (BMBF)/French Agence National de la Recherche (ANR) (SCD-Gene: 01KU0907) (to Dr Kaab), the BMBF cluster of excellence "personalized medicine M4" (to Dr Kaab), the National Institutes of Health and the Burroughs Wellcome Fund (to Dr Newton-Cheh), and the Academy of Finland grants 129494 and 139635 (to Dr Salomaa). This research used data and resources from the NHLBI's and Boston University School of Public Health's Framingham Heart Study (N01-HC-25195), its contract with Affymetrix, Inc, for genotyping services (contract number N02-HL-6-4278), and involved researchers participating in the SNP Health Association Resource (SHARe) project utilizing the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. Funding for analyses was provided by the NHLBI Division of Intramural Research (to Dr. O'Donnell, Dr Peloso, and Dr Hwang). The Health 2000 Study was funded by the National Institute for Health and Welfare (THL), the Finnish Centre for Pensions (ETK), The Social Insurance Institution of Finland (KELA), The Local Government Pensions Institution (KEVA), and other organizations listed on the Web site of the survey (http://www.terveys2000.fi). GWAS genotyping was supported by the Wellcome Trust Sanger Institute. The MONICA/KORA Augsburg studies were financed by the Helmholtz Zentrum Munchen, German Research Center for Environmental Health, Neuherberg, Germany, and supported by grants from the BMBF and the state of Bavaria. Additional support was provided from the BMBF in the context of NGFN plus (01GS0838), the LMU Excellence Initiative, and the Munich Center of Health Sciences (MC Health) as part of LMUinnovativ. The Young Finns Study was financed by the Academy of Finland: grants 134309 (Eye), 126925, 121584, 124282, and 129378 (Salve), 117787 (Gendi), and 41071 (Skidi), the Social Insurance Institution of Finland, Kuopio, Tampere, and Turku University Hospital Medical Funds (grants 9M048 and 9N035 for TeLeht), Juho Vainio Foundation, Paavo Nurmi Foundation, Finnish Foundation of Cardiovascular Research and Finnish Cultural Foundation, Tampere Tuberculosis Foundation, and Emil Aaltonen Foundation (TL). The project of "Genetic Park of FVG" was supported by Regione FVG (L.26.2008) and the Associazione Amici del Cuore. Dr Newton-Cheh reports to be on the scientific advisory board of Merck, Inc. Address for reprint requests and correspondence: Dr Christopher Newton-Cheh, MD, MPH, Center for Human Genetic Research, Cardiovascular Research Center, Massachusetts General Hospital, 185 Cambridge St, CPZN 5.242, Boston, MA 02114. E-mail address: cnewtoncheh@partners.org. NR 32 TC 20 Z9 21 U1 1 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD OCT PY 2012 VL 9 IS 10 BP 1627 EP 1634 DI 10.1016/j.hrthm.2012.06.008 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 013FZ UT WOS:000309292600011 PM 22683750 ER PT J AU Ajiboye, AB Simeral, JD Donoghue, JP Hochberg, LR Kirsch, RF AF Ajiboye, A. Bolu Simeral, John D. Donoghue, John P. Hochberg, Leigh R. Kirsch, Robert F. TI Prediction of Imagined Single-Joint Movements in a Person With High-Level Tetraplegia SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Brain-computer interface (BCI); BrainGate; local field potential (LFP); motor imagery; paralysis; spike ID LOCAL-FIELD POTENTIALS; PRIMARY MOTOR CORTEX; BRAIN-MACHINE INTERFACE; FREE ARM MOVEMENTS; NEURONAL POPULATION; 3-DIMENSIONAL SPACE; GRASP KINEMATICS; CORTICAL-NEURONS; SPIKING ACTIVITY; VISUAL TARGETS AB Cortical neuroprostheses for movement restoration require developing models for relating neural activity to desired movement. Previous studies have focused on correlating single-unit activities (SUA) in primary motor cortex to volitional arm movements in able-bodied primates. The extent of the cortical information relevant to arm movements remaining in severely paralyzed individuals is largely unknown. We record intracortical signals using a microelectrode array chronically implanted in the precentral gyrus of a person with tetraplegia, and estimate positions of imagined single-joint arm movements. Using visually guided motor imagery, the participant imagined performing eight distinct single-joint arm movements, while SUA, multispike trains (MSP), multiunit activity, and local field potential time (LFPrms), and frequency signals (LFPstft) were recorded. Using linear system identification, imagined joint trajectories were estimated with 20-60% variance explained, with wrist flexion/extension predicted the best and pronation/supination the poorest. Statistically, decoding of MSP and LFPstft yielded estimates that equaled those of SUA. Including multiple signal types in a decoder increased prediction accuracy in all cases. We conclude that signals recorded from a single restricted region of the precentral gyrus in this person with tetraplegia contained useful information regarding the intended movements of upper extremity joints. C1 [Ajiboye, A. Bolu; Kirsch, Robert F.] Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA. [Ajiboye, A. Bolu; Kirsch, Robert F.] Dept Vet Affairs Cleveland VA Med Ctr, RR&D, FES Ctr Excellence, Cleveland, OH 44106 USA. [Simeral, John D.; Donoghue, John P.; Hochberg, Leigh R.] Providence VA Med Ctr, Dept Vet Affairs Rehabil Res & Dev Serv, Providence, RI 02908 USA. [Simeral, John D.] Brown Univ, Sch Engn, Providence, RI 02912 USA. [Donoghue, John P.] Brown Univ, Inst Brain Sci Program, Dept Neurosci, Providence, RI 02912 USA. [Hochberg, Leigh R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Massachusetts Gen Hosp,Dept Neurol, Boston, MA 02114 USA. [Hochberg, Leigh R.] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Boston, MA 02114 USA. [Hochberg, Leigh R.] Brown Univ, Dept Neurosci Brain Sci Program, Providence, RI 02912 USA. RP Ajiboye, AB (reprint author), Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA. EM aba20@case.edu; john_simeral@brown.edu; john_donoghue@brown.edu; leigh_hochberg@brown.edu; rfk3@case.edu FU Department of Veterans Affairs Rehabilitation Research and Development Service (RRD); National Institute of Health (NIH) through the Eunice Kennedy Shriver National Institute on Child Health and Human Development (NICHD) [N01-HD-53403]; RR&D, Office of Research and Development, Department of Veterans Affairs [B6453R, A6779I]; NIH through the NICHD [RC1HD063931]; NIH through the National Institute on Neurological Disorders and Stroke [R01NS-25074]; NIH through the National Institute of Biomedical Imaging and Bioengineering [R01EB007401-01]; NIH through the National Institute on Deafness and Other Communication Disorders [R01DC009899]; NIH through the National Center for Research Resources [C06-16549-01A1]; Doris Duke Charitable Foundation; MGH-Deane Institute of Integrated Research on Atrial Fibrillation and Stroke; Katie Samson Foundation FX The work of A. B. Ajiboye was supported by a Career Development Award-1 through the Department of Veterans Affairs Rehabilitation Research and Development Service (RR&D). This work was primarily supported by the National Institute of Health (NIH) through the Eunice Kennedy Shriver National Institute on Child Health and Human Development (NICHD, N01-HD-53403). This study was enabled through additional support for the BrainGate2 pilot clinical trial by RR&D, Office of Research and Development, Department of Veterans Affairs (Merit Review Awards: B6453R and A6779I) and by the NIH through the NICHD (RC1HD063931), the National Institute on Neurological Disorders and Stroke (R01NS-25074), the National Institute of Biomedical Imaging and Bioengineering (R01EB007401-01), the National Institute on Deafness and Other Communication Disorders (R01DC009899), and the National Center for Research Resources (C06-16549-01A1). This work was also supported in part by the Doris Duke Charitable Foundation, the MGH-Deane Institute of Integrated Research on Atrial Fibrillation and Stroke, and the Katie Samson Foundation. Asterisk indicates corresponding author. NR 53 TC 14 Z9 16 U1 1 U2 12 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD OCT PY 2012 VL 59 IS 10 BP 2755 EP 2765 DI 10.1109/TBME.2012.2209882 PG 11 WC Engineering, Biomedical SC Engineering GA 008XD UT WOS:000308989000008 PM 22851229 ER PT J AU Citi, L Brown, EN Barbieri, R AF Citi, Luca Brown, Emery N. Barbieri, Riccardo TI A Real-Time Automated Point-Process Method for the Detection and Correction of Erroneous and Ectopic Heartbeats SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Arrhythmias; ectopic beats; erroneous R-R intervals; heart rate variability; point processes ID RATE-VARIABILITY; SPECTRAL-ANALYSIS; INTERBEAT INTERVALS; TIMING SIGNAL; MODEL; ARRHYTHMIA; ARTIFACT AB The presence of recurring arrhythmic events (also known as cardiac dysrhythmia or irregular heartbeats), as well as erroneous beat detection due to low signal quality, significantly affects estimation of both time and frequency domain indices of heart rate variability (HRV). A reliable, real-time classification and correction of ECG-derived heartbeats is a necessary prerequisite for an accurate online monitoring of HRV and cardiovascular control. We have developed a novel point-process-based method for real-time R-R interval error detection and correction. Given an R-wave event, we assume that the length of the next R-R interval follows a physiologically motivated, time-varying inverse Gaussian probability distribution. We then devise an instantaneous automated detection and correction procedure for erroneous and arrhythmic beats by using the information on the probability of occurrence of the observed beat provided by the model. We test our algorithm over two datasets from the PhysioNet archive. The Fantasia normal rhythm database is artificially corrupted with known erroneous beats to test both the detection procedure and correction procedure. The benchmark MIT-BIH Arrhythmia database is further considered to test the detection procedure of real arrhythmic events and compare it with results from previously published algorithms. Our automated algorithm represents an improvement over previous procedures, with best specificity for the detection of correct beats, as well as highest sensitivity to missed and extra beats, artificially misplaced beats, and for real arrhythmic events. A near-optimal heartbeat classification and correction, together with the ability to adapt to time-varying changes of heartbeat dynamics in an online fashion, may provide a solid base for building a more reliable real-time HRV monitoring device. C1 [Citi, Luca; Brown, Emery N.; Barbieri, Riccardo] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02115 USA. [Citi, Luca; Brown, Emery N.; Barbieri, Riccardo] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Citi, L (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02115 USA. EM lciti@neurostat.mit.edu; enb@neurostat.mit.edu; barbieri@neurostat.mit.edu RI Citi, Luca/G-2270-2011; OI Citi, Luca/0000-0001-8702-5654; Barbieri, Riccardo/0000-0001-9381-3833 FU National Institutes of Health (NIH) [R01-HL084502, DP1-OD003646] FX The work of R. Barbieri was supported by the National Institutes of Health (NIH) under Grant R01-HL084502. The work of E. N. Brown was supported by the NIH under Grant DP1-OD003646. Asterisk indicates corresponding author. NR 40 TC 17 Z9 17 U1 0 U2 9 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD OCT PY 2012 VL 59 IS 10 BP 2828 EP 2837 DI 10.1109/TBME.2012.2211356 PG 10 WC Engineering, Biomedical SC Engineering GA 008XD UT WOS:000308989000016 PM 22875239 ER PT J AU Kim, CH Ahn, JH Lee, KB Jung, C Park, HG Choi, YK AF Kim, Chang-Hoon Ahn, Jae-Hyuk Lee, Kyung-Bok Jung, Cheulhee Park, Hyun Gyu Choi, Yang-Kyu TI A New Sensing Metric to Reduce Data Fluctuations in a Nanogap-Embedded Field-Effect Transistor Biosensor SO IEEE TRANSACTIONS ON ELECTRON DEVICES LA English DT Article DE Coefficient of variation (CV); drain current; field-effect transistor (FET)-based biosensor; impact ionization; label free; nanogap; nanogap-embedded FET; peptide nucleic acid (PNA); reliability; substrate current; threshold voltage ID SILICON NANOWIRE BIOSENSORS; ELECTRICAL DETECTION; HYBRIDIZATION; SENSORS AB A new sensing metric is proposed for a field-effect transistor (FET)-based biosensor. As proof of concept, a nanogap-embedded FET is studied to reduce data fluctuations that originate from process variations during FET fabrication and environmental variations stemming from bioexperiments. The new sensing metric utilizes a crucial gate voltage (V-G@I-sub,I-max), which induces the maximum substrate current. The new sensing metric shows higher immunity against variations of the nanogap length, compared with the commonly used metric that relies on threshold voltage or drain current. The proposed metric also shows smaller fluctuation, which is caused by environmental variation coming from biotreatment steps. This analysis is verified experimentally and proved by device simulations. For simple analysis, the effect of external charge of the biomolecules is eliminated by using peptide nucleic acid, which is an electrically neutral biomolecule. Thus, by using such biomolecules, the permittivity effect rising from the biomolecules within the nanogap of the gate dielectric is investigated. C1 [Kim, Chang-Hoon; Ahn, Jae-Hyuk; Jung, Cheulhee; Park, Hyun Gyu; Choi, Yang-Kyu] Korea Adv Inst Sci & Technol, Taejon 305701, South Korea. [Lee, Kyung-Bok] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Kim, CH (reprint author), Korea Adv Inst Sci & Technol, Taejon 305701, South Korea. EM ykchoi@ee.kaist.ac.kr RI PARK, HYUN GYU/C-1597-2011; Jung, Cheulhee/D-2726-2017 FU National Research and Development Program [2012-0001131]; Center for Integrated Smart Sensors; Basic Science Research Program through the National Research Foundation of Korea; Ministry of Education, Science, and Technology [CISS-2011-0031845, 2009-008062] FX Manuscript received October 4, 2011; revised May 21, 2012; accepted July 13, 2012. Date of publication August 15, 2012; date of current version September 18, 2012. This work was supported in part by the National Research and Development Program under Grant 2012-0001131 for the development of biomedical function monitoring biosensors and by the Center for Integrated Smart Sensors and the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology under Grant CISS-2011-0031845 and Grant 2009-008062, respectively. The review of this paper was arranged by Editor A. M. Ionescu. NR 18 TC 5 Z9 5 U1 1 U2 21 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9383 J9 IEEE T ELECTRON DEV JI IEEE Trans. Electron Devices PD OCT PY 2012 VL 59 IS 10 BP 2825 EP 2831 DI 10.1109/TED.2012.2209650 PG 7 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA 010ZD UT WOS:000309132200037 ER PT J AU Ferguson, ND Fan, E Camporota, L Antonelli, M Anzueto, A Beale, R Brochard, L Brower, R Esteban, A Gattinoni, L Rhodes, A Slutsky, AS Vincent, JL Rubenfeld, GD Thompson, BT Ranieri, VM AF Ferguson, Niall D. Fan, Eddy Camporota, Luigi Antonelli, Massimo Anzueto, Antonio Beale, Richard Brochard, Laurent Brower, Roy Esteban, Andres Gattinoni, Luciano Rhodes, Andrew Slutsky, Arthur S. Vincent, Jean-Louis Rubenfeld, Gordon D. Thompson, B. Taylor Ranieri, V. Marco TI The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material SO INTENSIVE CARE MEDICINE LA English DT Article DE Diagnosis; International cooperation; Prognosis; Respiration, artificial; Respiratory distress syndrome, adult; Risk factors ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; EUROPEAN CONSENSUS CONFERENCE; PROTECTIVE VENTILATION; PULMONARY-ARTERY; CLINICAL-TRIAL; VARIABILITY; TOMOGRAPHY; OUTCOMES; BIOPSY AB Our objective was to revise the definition of acute respiratory distress syndrome (ARDS) using a conceptual model incorporating reliability and validity, and a novel iterative approach with formal evaluation of the definition. The European Society of Intensive Care Medicine identified three chairs with broad expertise in ARDS who selected the participants and created the agenda. After 2 days of consensus discussions a draft definition was developed, which then underwent empiric evaluation followed by consensus revision. The Berlin Definition of ARDS maintains a link to prior definitions with diagnostic criteria of timing, chest imaging, origin of edema, and hypoxemia. Patients may have ARDS if the onset is within 1 week of a known clinical insult or new/worsening respiratory symptoms. For the bilateral opacities on chest radiograph criterion, a reference set of chest radiographs has been developed to enhance inter-observer reliability. The pulmonary artery wedge pressure criterion for hydrostatic edema was removed, and illustrative vignettes were created to guide judgments about the primary cause of respiratory failure. If no risk factor for ARDS is apparent, however, objective evaluation (e.g., echocardiography) is required to help rule out hydrostatic edema. A minimum level of positive end-expiratory pressure and mutually exclusive PaO2/FiO(2) thresholds were chosen for the different levels of ARDS severity (mild, moderate, severe) to better categorize patients with different outcomes and potential responses to therapy. This panel addressed some of the limitations of the prior ARDS definition by incorporating current data, physiologic concepts, and clinical trials results to develop the Berlin definition, which should facilitate case recognition and better match treatment options to severity in both research trials and clinical practice. C1 [Ferguson, Niall D.; Fan, Eddy] Univ Hlth Network, Interdept Div Crit Care Med, Toronto, ON M5G 1X5, Canada. [Ferguson, Niall D.] Univ Hlth Network, Dept Med, Div Respirol, Toronto, ON M5G 1X5, Canada. [Ferguson, Niall D.; Fan, Eddy] Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Camporota, Luigi; Beale, Richard] Kings Coll London, Div Asthma Allergy & Lung Biol, London WC2R 2LS, England. [Camporota, Luigi; Beale, Richard] Guys & St Thomas NHS Fdn Trust, Dept Adult Crit Care, Kings Hlth Partners, London, England. [Antonelli, Massimo] Univ Cattolica Sacro Cuore, Dipartimento Anestesia & Rianimaz, Rome, Italy. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA. [Anzueto, Antonio] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Brochard, Laurent] Hop Cantonal Univ Geneva, Med Surg Intens Care Unit, Geneva, Switzerland. [Brower, Roy] Johns Hopkins Univ, Div Pulm & Crit Care Med, Baltimore, MD USA. [Esteban, Andres] Hosp Univ Getafe, Serv Cuidados Intens, Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. [Gattinoni, Luciano] Univ Milan, Ist Anestesiol & Rianimaz, Milan, Italy. [Rhodes, Andrew] St Georges Healthcare NHS Trust, Dept Intens Care Med, London, England. [Slutsky, Arthur S.] Univ Toronto, St Michaels Hosp, Li KaShing Knowledge Inst, Interdept Div Crit Care Med,Keenan Res Ctr, Toronto, ON M5B 1W8, Canada. [Vincent, Jean-Louis] Univ Libre Brussels, Erasme Univ Hosp, Dept Intens Care, Brussels, Belgium. [Thompson, B. Taylor] Massachusetts Gen Hosp, Dept Med, Pulm Crit Care Unit, Boston, MA 02114 USA. [Thompson, B. Taylor] Harvard Univ, Sch Med, Boston, MA USA. [Ranieri, V. Marco] Univ Turin, Dept Anesthesia & Intens Care Med, Turin, Italy. RP Ferguson, ND (reprint author), Univ Hlth Network, Interdept Div Crit Care Med, 600 Univ Ave,Suite 18-206, Toronto, ON M5G 1X5, Canada. EM n.ferguson@utoronto.ca RI Beale, Richard/J-7831-2013; Antonelli, Massimo/K-9915-2016; OI Antonelli, Massimo/0000-0003-3007-1670; Ferguson, Niall/0000-0002-6213-5264 FU European Society of Intensive Care Medicine (ESICM); Canadian Institutes of Health Research (Ottawa, Canada); National Institutes of Health (Bethesda, USA) [R01HL067939] FX All authors have completed and submitted disclosure forms regarding their potential conflicts of interest. The meeting was convened and supported financially by the European Society of Intensive Care Medicine (ESICM). Dr. Ferguson is supported by a Canadian Institutes of Health Research New Investigator Award (Ottawa, Canada). Dr. Fan is supported by a Canadian Institutes of Health Research Fellowship Award (Ottawa, Canada). Dr. Rubenfeld is supported by the National Institutes of Health grant R01HL067939 (Bethesda, USA). None of the funding organizations or sponsors had any role in the design and conduct of the study; the collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript. NR 48 TC 237 Z9 276 U1 5 U2 47 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD OCT PY 2012 VL 38 IS 10 BP 1573 EP 1582 DI 10.1007/s00134-012-2682-1 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 008LA UT WOS:000308957300001 PM 22926653 ER PT J AU Ferguson, ND Fan, E Camporota, L Antonelli, M Anzueto, A Beale, R Brochard, L Brower, R Esteban, A Gattinoni, L Rhodes, A Slutsky, AS Vincent, JL Rubenfeld, GD Thompson, BT Ranieri, VM AF Ferguson, Niall D. Fan, Eddy Camporota, Luigi Antonelli, Massimo Anzueto, Antonio Beale, Richard Brochard, Laurent Brower, Roy Esteban, Andres Gattinoni, Luciano Rhodes, Andrew Slutsky, Arthur S. Vincent, Jean-Louis Rubenfeld, Gordon D. Thompson, B. Taylor Ranieri, V. Marco TI The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material (vol 38, pg 1573, 2012) SO INTENSIVE CARE MEDICINE LA English DT Correction C1 [Ferguson, Niall D.; Fan, Eddy] Univ Hlth Network, Interdept Div Crit Care Med, Toronto, ON M5G 1X5, Canada. [Ferguson, Niall D.] Univ Hlth Network, Dept Med, Div Respirol, Toronto, ON M5G 1X5, Canada. [Ferguson, Niall D.; Fan, Eddy] Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Camporota, Luigi; Beale, Richard] Kings Coll London, Div Asthma Allergy & Lung Biol, London WC2R 2LS, England. [Camporota, Luigi; Beale, Richard] Kings Hlth Partners, Guys & St Thomas NHS Fdn Trust, Dept Adult Crit Care, London, England. [Antonelli, Massimo] Univ Cattolica Sacro Cuore, Dipartimento Anestesia & Rianimaz, Rome, Italy. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Anzueto, Antonio] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Brochard, Laurent] Hop Univ Geneve, Med Surg Intens Care Unit, Geneva, Switzerland. [Brower, Roy] Johns Hopkins Univ, Div Pulm & Crit Care Med, Baltimore, MD USA. [Esteban, Andres] Hosp Univ Getafe, Inst Salud Carlos III, CIBER Enfermedades Resp, Serv Cuidados Intens, Madrid, Spain. [Gattinoni, Luciano] Univ Milan, Ist Anestesiol & Rianimaz, Milan, Italy. [Rhodes, Andrew] St Georges Healthcare NHS Trust, Dept Intens Care Med, London, England. [Slutsky, Arthur S.] St Michaels Hosp, Li KaShing Knowledge Inst, Keenan Res Ctr, Toronto, ON M5B 1W8, Canada. [Slutsky, Arthur S.; Rubenfeld, Gordon D.] Univ Toronto, Interdept Div Crit Care Med, Toronto, ON, Canada. [Vincent, Jean-Louis] Univ Libre Brussels, Erasme Univ Hosp, Dept Intens Care, Brussels, Belgium. [Thompson, B. Taylor] Massachusetts Gen Hosp, Dept Med, Pulm Crit Care Unit, Boston, MA 02114 USA. [Thompson, B. Taylor] Harvard Univ, Sch Med, Boston, MA USA. [Ranieri, V. Marco] Univ Turin, Dept Anesthesia & Intens Care Med, Turin, Italy. RP Ferguson, ND (reprint author), Univ Hlth Network, Interdept Div Crit Care Med, 600 Univ Ave,Suite 18-206, Toronto, ON M5G 1X5, Canada. EM n.ferguson@utoronto.ca RI Beale, Richard/J-7831-2013 NR 1 TC 5 Z9 7 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD OCT PY 2012 VL 38 IS 10 BP 1731 EP 1732 DI 10.1007/s00134-012-2698-6 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 008LA UT WOS:000308957300027 ER PT J AU Saunders, GH Forsline, A AF Saunders, Gabrielle H. Forsline, Anna TI Hearing-aid counseling: Comparison of single-session informational counseling with single-session performance-perceptual counseling SO INTERNATIONAL JOURNAL OF AUDIOLOGY LA English DT Article DE Hearing aids; rehabilitation of hearing impaired; counseling ID MEDICAL INFORMATION; REPORTED HANDICAP; OLDER-PEOPLE; ADULTS; USERS; IMPAIRMENT; OUTCOMES; PROGRAM; MEMORY; INVENTORY AB Objective: Hearing-aid counseling can improve outcome but programs are often too resource-intensive to be clinically practical. Here we examined the effectiveness of single-session informational counseling with single-session performance-perceptual counseling. Design: Two forms of counseling were compared: informational counseling (IC) and performance-perceptual counseling (PPC). IC focused on discussing communication strategies and tips for hearing-aid use. PPC addressed the discrepancy between measured and perceived ability to understand speech. Outcomes were measured eight-to-ten weeks post-counseling using quantitative and qualitative measures: Hearing handicap inventory, abbreviated profile of hearing aid benefit, psychosocial impact of assistive devices scale (PIADS), international outcome inventory for hearing aids, and a semi-structured exit interview. Study sample: Seventy-four hearing aid-users with symmetrical sensorineural hearing loss participated. Results: Scores on the hearing questionnaires showed no change following either form of counseling. Scores on the PIADS improved for participants as a whole, and the semi-structured interview revealed increased hearing-aid use, better understanding and acceptance of hearing loss, increased use of communication strategies, and improved ability to explain hearing difficulties to others. Conclusions: A single session of hearing-aid counseling can improve hearing-aid use and satisfaction. Open-ended interview and/or quality of life measures are more sensitive to these benefits than hearing questionnaires. C1 [Saunders, Gabrielle H.] Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, Portland, OR 97239 USA. [Forsline, Anna] Portland VA Med Ctr, Dept Audiol & Speech Pathol, Portland, OR 97239 USA. RP Saunders, GH (reprint author), Portland VA Med Ctr, Natl Ctr Rehabil Auditory Res, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM gabrielle.saunders@va.gov FU Department of Veterans Affairs Health Administration, Rehabilitation Research and Development Grant [C3951R]; National Center for Rehabilitative Auditory Research, Portland VA Medical Center, Portland, Oregon FX The research reported here was supported by the Department of Veterans Affairs Health Administration, Rehabilitation Research and Development Grant # C3951R and the National Center for Rehabilitative Auditory Research, Portland VA Medical Center, Portland, Oregon. We thank Mark Caldwell and ShienPei Silverman for their participation with data collection and administrative support. Data from this work have been presented at the 2008 International Hearing Aid Research Conference (IHCON), Lake Tahoe, USA August 13-15, 2008; and at the 5th International Adult Aural Rehabilitation Conference, Tampa Florida, USA, March 16-19, 2009. NR 45 TC 7 Z9 7 U1 0 U2 12 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1499-2027 J9 INT J AUDIOL JI Int. J. Audiol. PD OCT PY 2012 VL 51 IS 10 BP 754 EP 764 DI 10.3109/14992027.2012.699200 PG 11 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 010NZ UT WOS:000309102500007 PM 22812927 ER PT J AU Liersch, R Shin, JW Bayer, M Schwoppe, C Schliemann, C Berdel, WE Mesters, R Detmar, M AF Liersch, Ruediger Shin, Jay W. Bayer, Michael Schwoeppe, Christian Schliemann, Chrstoph Berdel, Wolfgang E. Mesters, Rolf Detmar, Michael TI Analysis of a novel highly metastatic melanoma cell line identifies osteopontin as a new lymphangiogenic factor SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE lymphatic endothelial cells; osteopontin; lymphangiogenesis; metastasis; cancer ID LYMPH-NODE LYMPHANGIOGENESIS; PROMOTES TUMOR-METASTASIS; PROGNOSTIC-FACTORS; BREAST-CANCER; EXPRESSION; GROWTH; MIGRATION; GENES; ANGIOGENESIS; PROGRESSION AB Tumor cell invasion and metastasis are hallmarks of malignancy. Despite recent advances in the understanding of lymphatic spread, the mechanisms by which tumors metastasize to sentinel/distant lymph nodes and beyond are poorly understood. To gain new insights into this complex process, we established highly metastatic melanoma cell lines by in vivo passaging the B16 parental cell line through the lymphatic system. In this study we characterized morphology, rate of cell proliferation, colony formation, migration, tumorigenicity, lymph flow, and capacities to induce tumor- and sentinel lymph node-lymphangiogenesis. Furthermore, microarray-based comparative analysis between parental and passaged cell lines was performed to identify specific gene expression profiles. The most differentially expressed gene was SPP (osteopontin), a secreted glycophosphoprotein which is known to be involved in cancer metastasis. Overexpression of osteopontin in B16 F1-variant was confirmed by western blot analysis and quantitative RT-PCR. Treatment of cultured lymphatic endothelial cells (LECs) with osteopontin promoted cell migration mediated by the integrin alpha 9 pathway. Our results identify osteopontin as a novel lymphangiogenic factor. C1 [Liersch, Ruediger; Bayer, Michael; Schwoeppe, Christian; Schliemann, Chrstoph; Berdel, Wolfgang E.; Mesters, Rolf] Univ Hosp Muenster, Dept Med Hematol & Oncol, D-48129 Muenster, Germany;. [Shin, Jay W.; Detmar, Michael] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Shin, Jay W.; Detmar, Michael] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Swiss Fed Inst Technol, Inst Pharmaceut Sci, CH-8092 Zurich, Switzerland. RP Liersch, R (reprint author), Univ Munster, Dept Med Hematol & Oncol, Albert Schweitzer Campus 1, D-48149 Munster, Germany. EM rliersch@uni-muenster.de FU NIH [CA69184, CA86410, CA92644]; American Cancer Society Research [99-23901]; Swiss National Science Foundation [3100A0-108207, 31003A_130627]; Krebsliga Schweiz; Krebsliga Zurich; Fonds fur wissenschaftliche Forderung grant [S9408-B11]; Deutsche Krebshilfe; Deutsche Forschungsgemeinschaft (DFG) [SPPI190] FX We thank J. Zielinski, L. Janes, L. Nguyen, N. Fehrmann and M. Raedel for expert technical assistance. This study was supported by NIH grants CA69184, CA86410, CA92644 (MD), American Cancer Society Research Project Grant 99-23901 (MD), Swiss National Science Foundation grants 3100A0-108207 and 31003A_130627, Krebsliga Schweiz, Krebsliga Zurich, Fonds fur wissenschaftliche Forderung grant S9408-B11 (MD), and by the Deutsche Krebshilfe (RL). RL was supported by the Deutsche Forschungsgemeinschaft (DFG) -SPPI190. NR 41 TC 7 Z9 7 U1 0 U2 5 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD OCT PY 2012 VL 41 IS 4 BP 1455 EP 1463 DI 10.3892/ijo.2012.1548 PG 9 WC Oncology SC Oncology GA 013IA UT WOS:000309297900032 PM 22797548 ER PT J AU Pedamallu, CS Ozdamar, L Akar, H Weber, GW Ozsoy, A AF Pedamallu, Chandra Sekhar Ozdamar, Linet Akar, Hanife Weber, Gerhard-Wilhelm Ozsoy, Aysegul TI Investigating academic performance of migrant students: A system dynamics perspective with an application to Turkey SO INTERNATIONAL JOURNAL OF PRODUCTION ECONOMICS LA English DT Article DE Developing countries; Emigration; Poverty; Government policy; Education; Systems dynamics; Operational Research ID CROSS-IMPACT ANALYSIS; MIGRATION AB The system dynamics approach is a holistic way of solving problems in real-time scenarios. This is a powerful methodology of modern Operational Research for framing, analyzing, and discussing complex issues and problems. System dynamics modeling is often the background of a systemic thinking approach and has become a management and organizational development paradigm. This paper proposes a system dynamics model for studying the factors that impact the academic performance of 1st to 8th grade primary school students residing in poor migrant neighborhoods. The data used in the model are based upon the perception of teachers who are the subjects of a survey conducted in public schools located mainly in the inner squatter and outer squatter districts of Turkish cities. Squatter districts are subjected to large shifts of population as a result of interregional and urban-rural migration, and they pose educational, social and behavioral challenges. The system dynamics model proposed here builds up relationships between variables that affect academic performance of migrant students. The goal of the model is to identify best government policies that might improve the system state in the minimum time span. System simulation results show that the government should implement policies that target many aspects of the system concurrently in order to improve student academic quality. (c) 2011 Elsevier B.V. All rights reserved. C1 [Weber, Gerhard-Wilhelm] Middle E Tech Univ, Inst Appl Math, TR-06531 Ankara, Turkey. [Pedamallu, Chandra Sekhar] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Pedamallu, Chandra Sekhar] Broad Inst MIT & Harvard, Cambridge, MA USA. [Ozdamar, Linet] Yeditepe Univ, Dept Syst Engn, TR-34755 Istanbul, Turkey. [Akar, Hanife; Ozsoy, Aysegul] Middle E Tech Univ, Dept Educ Sci, TR-06531 Ankara, Turkey. RP Weber, GW (reprint author), Middle E Tech Univ, Inst Appl Math, TR-06531 Ankara, Turkey. EM pcs.murali@gmail.com; ozdamar@yeditepe.edu.tr; hanif@metu.edu.tr; gweber@metu.edu.tr; misirli@metu.edu.tr.tr RI Lin, yu/H-5022-2014 NR 38 TC 1 Z9 1 U1 1 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-5273 J9 INT J PROD ECON JI Int. J. Prod. Econ. PD OCT PY 2012 VL 139 IS 2 BP 422 EP 430 DI 10.1016/j.ijpe.2011.03.016 PG 9 WC Engineering, Industrial; Engineering, Manufacturing; Operations Research & Management Science SC Engineering; Operations Research & Management Science GA 001GS UT WOS:000308449200006 ER PT J AU Ellis, C Grubaugh, AL Egede, LE AF Ellis, Charles Grubaugh, Anouk L. Egede, Leonard E. TI The association between major depression, health behaviors, and quality of life in adults with stroke SO INTERNATIONAL JOURNAL OF STROKE LA English DT Article DE depression; quality of life; stroke ID RISK-FACTOR SURVEY; POSTSTROKE DEPRESSION; FOLLOW-UP; SURVIVORS; SATISFACTION; SYMPTOMS; CAREGIVERS; REHABILITATION; RELIABILITY; POPULATION AB Aim The study aims to examine the association between major depression, healthcare behaviors, and quality of life indices among adults with stroke. Methods Data from 5869 participants with stroke in the 2006 Behavioral Risk Factor Surveillance Survey were examined. Multiple logistic regression was used to assess the independent association between depression status, self-care and preventive health behaviors, and quality of life indices, after accounting for relevant covariates. Results In multivariate models, individuals with major depression were less likely to engage in physical activity (odds ratio 0.41; 95% confidence interval 0.29, 0.56) than those without major depression. Women with major depression were also less likely to have received a mammogram in the past two-years (odds ratio 0.61; 95% confidence interval 0.40, 0.96 for women?=?age 40 and odds ratio 0.58; 95% confidence interval 0.36, 0.72 for women?=?age 50) and a pap smear in the past three-years (odds ratio 0.40; 95% CI 0.22, 0.72). In comparisons of quality of life, individuals with major depression were less likely to perceive their health as excellent/very good/good (odds ratio 0.36; 95% confidence interval 0.25, 0.53), to report being satisfied with life (odds ratio 0.13; 95% confidence interval 0.08, 0.20), and to report receiving needed social support (odds ratio 0.42; 95% confidence interval 0.28, 0.63). Individuals who were depressed were also more likely to report one or more poor physical and poor mental health days in the past 30 days (odds ratio 4.56; 95% confidence interval 3.08, 6.76 and odds ratio 10.97; 95% confidence interval 7.75, 15.52, respectively). Conclusions In adults with stroke, major depression is associated with decreased engagement in stroke-specific and gender-specific self-care and preventive health behaviors, as well as a broad range of quality of life indices. C1 [Ellis, Charles] Med Univ S Carolina, Coll Hlth Profess, Dept Hlth Sci & Res, Charleston, SC 29425 USA. [Ellis, Charles; Grubaugh, Anouk L.; Egede, Leonard E.] Ralph H Johnson VA Med Ctr, VA Ctr Dis Prevent & Hlth Intervent Div Populat, Charleston, SC USA. [Grubaugh, Anouk L.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Egede, Leonard E.] Med Univ S Carolina, Dept Med, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. RP Ellis, C (reprint author), Med Univ S Carolina, Coll Hlth Profess, Dept Hlth Sci & Res, 77 President St,MSC 700, Charleston, SC 29425 USA. EM ellisc@musc.edu FU Charleston, SC HSR& D Funded Center for Disease Prevention and Health Interventions for Diverse Populations [REA 08-261]; Veterans Health Administration Health Services Research and Development program [07-012-3, 07-015-2] FX (1) This work represents work supported by the use of facilities at the Charleston, SC HSR& D Funded Center for Disease Prevention and Health Interventions for Diverse Populations (REA 08-261).; (2) Dr Ellis is supported by a career development award (CDA# 07-012-3) from the Veterans Health Administration Health Services Research and Development program.; (3) Dr Grubaugh is supported by a career development award (CDA2 # 07-015-2) from the Veterans Health Administration Health Services Research and Development program. NR 40 TC 4 Z9 5 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1747-4930 J9 INT J STROKE JI Int. J. Stroke PD OCT PY 2012 VL 7 IS 7 BP 536 EP 543 DI 10.1111/j.1747-4949.2011.00708.x PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 008PD UT WOS:000308968100011 PM 22151696 ER PT J AU Goldvasser, D Noz, ME Maguire, GQ Olivecrona, H Bragdon, CR Makhau, H AF Goldvasser, Dov Noz, Marilyn E. Maguire, G. Q., Jr. Olivecrona, Henrik Bragdon, Charles R. Makhau, Henrik TI A New Technique for Measuring Wear in Total Hip Arthroplasty Using Computed Tomography SO JOURNAL OF ARTHROPLASTY LA English DT Article DE hip phantom; polyethylene wear; high-resolution CT scanners; error measurement; precision measurement ID FEMORAL-HEAD PENETRATION; POLYETHYLENE WEAR; CT; REPLACEMENT AB Accurately estimating polyethylene wear in 3 dimensions, without the need for additional procedures or equipment, is of significant interest. We investigated the use of a high-resolution clinical computed tomographic (CT) scanner to estimate femoral head displacement relative to the cup as an indirect method of estimating polyethylene wear. A hip phantom was used to simulate the 3-dimensional displacement of a femoral head. The phantom was imaged in a high-resolution CT scanner. The mean difference between the true phantom displacement as positioned by micrometers and the calculated displacement based on the CT images was as follows: for the x-axis, 0 mm (SD, 0.213; SE, 0.058); y-axis, 0.039 mm (SD, 0.035; SE, 0.026); and z-axis, 0.039 mm (SD, 0.051; SE, 0.020). C1 [Goldvasser, Dov] Massachusetts Gen Hosp, Harris Orthopaed Labs, Boston, MA 02114 USA. [Goldvasser, Dov; Olivecrona, Henrik] Karolinska Inst, Dept Mol Med & Surg, Sect Orthopaed & Sport Med, Stockholm, Sweden. [Noz, Marilyn E.] NYU, Dept Radiol, New York, NY 10016 USA. [Maguire, G. Q., Jr.] KTH Royal Inst Technol, Sch Informat & Commun Technol, Kista, Sweden. RP Goldvasser, D (reprint author), Massachusetts Gen Hosp, Harris Orthopaed Labs, 55 Fruit St, Boston, MA 02114 USA. RI Maguire, Gerald/G-4584-2011; OI Maguire, Gerald/0000-0002-6066-746X; Malchau, Henrik/0000-0002-4291-2441 NR 16 TC 5 Z9 5 U1 0 U2 4 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 EI 1532-8406 J9 J ARTHROPLASTY JI J. Arthroplast. PD OCT PY 2012 VL 27 IS 9 BP 1636 EP 1640 DI 10.1016/j.arth.2012.03.053 PG 5 WC Orthopedics SC Orthopedics GA 013WA UT WOS:000309335400010 PM 22658429 ER PT J AU Severson, EP Singh, JA Browne, JA Trousdale, RT Sarr, MG Lewallen, DG AF Severson, Erik P. Singh, Jasvinder A. Browne, James A. Trousdale, Robert T. Sarr, Michael G. Lewallen, David G. TI Total Knee Arthroplasty in Morbidly Obese Patients Treated With Bariatric Surgery A Comparative Study SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total knee arthroplasty; morbidly obese; bariatric surgery; outcomes ID TOTAL JOINT ARTHROPLASTY; WEIGHT-LOSS; GASTRIC BYPASS; BONE TURNOVER; TOTAL HIP; COMPLICATIONS; REPLACEMENT; MECHANISMS; MARKERS AB Our objective was to compare outcomes (anesthesia time, total operative time, tourniquet time, duration of hospital stay, 90-day complication rate, and transfusion rates) of patients with total knee arthroplasty (TKA) who underwent bariatric surgery before or after TKA. One hundred twenty-five patients were included: TKA before bariatric surgery (group 1; n = 39), TKA within 2 years of bariatric surgery (group 2; n = 25), and TKA more than 2 years after bariatric surgery (group 3; n = 61). Patients with TKA more than 2 years after bariatric surgery had shorter anesthesia and total operative and tourniquet times than other groups; differences were significant between groups. Ninety-day complication and transfusion rates approached but did not meet statistical significance. Ninety-day complication rates and duration of hospital stay did not differ significantly between the 3 groups. The level of evidence was level II (cohort study). C1 [Singh, Jasvinder A.] Univ Alabama Birmingham, Fac Off, Sch Publ Hlth, Dept Med, Birmingham, AL 35294 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USA. [Severson, Erik P.] Minnesota Ctr Orthopaed, Crosby, MN USA. [Severson, Erik P.; Singh, Jasvinder A.; Trousdale, Robert T.; Lewallen, David G.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham VA Med Ctr, C SMART, Birmingham, AL USA. [Browne, James A.] Univ Virginia, Dept Orthopaed Surg, Charlottesville, VA USA. [Sarr, Michael G.] Mayo Clin, Coll Med, Dept Surg, Rochester, MN USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Fac Off, Sch Publ Hlth, Dept Med, Tower 805B,510 20th St S, Birmingham, AL 35294 USA. OI singh, jasvinder/0000-0003-3485-0006 FU NCRR NIH HHS [KL2 RR024151, KL2 RR024151-01] NR 28 TC 27 Z9 27 U1 2 U2 7 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD OCT PY 2012 VL 27 IS 9 BP 1696 EP 1700 DI 10.1016/j.arth.2012.03.005 PG 5 WC Orthopedics SC Orthopedics GA 013WA UT WOS:000309335400019 PM 22554730 ER PT J AU Zhao, WN Cheng, CL Theriault, KM Sheridan, SD Tsai, LH Haggarty, SJ AF Zhao, Wen-Ning Cheng, Chialin Theriault, Kraig M. Sheridan, Steven D. Tsai, Li-Huei Haggarty, Stephen J. TI A High-Throughput Screen for Wnt/beta-Catenin Signaling Pathway Modulators in Human iPSC-Derived Neural Progenitors SO JOURNAL OF BIOMOLECULAR SCREENING LA English DT Article DE induced pluripotent stem cell (iPSC); neural progenitor cell (NPC); Wnt/beta-catenin signaling; neuropsychiatric disorders; human neurons ID PLURIPOTENT STEM-CELLS; DRUG DISCOVERY; DEFINED FACTORS; LITHIUM; SCHIZOPHRENIA; INTEGRATION; PROLIFERATION; NEUROGENESIS; BEHAVIORS; ASSAYS AB Wnt/beta-catenin signaling has emerged as a central player in pathways implicated in the pathophysiology and treatment of neuropsychiatric disorders. To identify potential novel therapeutics for these disorders, high-throughput screening (HTS) assays reporting on Wnt/beta-catenin signaling in disease-relevant contexts are needed. The use of human patient-derived induced pluripotent stem cell (iPSC) models provides ideal disease-relevant context if these stem cell cultures can be adapted for HTS-compatible formats. Here, we describe a sensitive, HTS-compatible Wnt/beta-catenin signaling reporter system generated in homogeneous, expandable neural progenitor cells (NPCs) derived from human iPSCs. We validated this system by demonstrating dose-responsive stimulation by several known Wnt/beta-catenin signaling pathway modulators, including Wnt3a, a glycogen synthase kinase-3 (GSK3) inhibitor, and the bipolar disorder therapeutic lithium. These responses were robust and reproducible over time across many repeated assays. We then conducted a screen of similar to 1500 compounds from a library of Food and Drug Administration-approved drugs and known bioactives and confirmed the HTS hits, revealing multiple chemical and biological classes of novel small-molecule probes of Wnt/beta-catenin signaling. Generating these type of pathway-selective, cell-based phenotypic assays in human iPSC-derived neural cells will advance the field of human experimental neurobiology toward the goal of identifying and validating targets for neuropsychiatric disorders. C1 [Zhao, Wen-Ning; Cheng, Chialin; Theriault, Kraig M.; Sheridan, Steven D.; Haggarty, Stephen J.] Harvard Univ, Sch Med, Ctr Human Genet Res, Dept Neurol, Boston, MA 02114 USA. [Zhao, Wen-Ning; Cheng, Chialin; Theriault, Kraig M.; Sheridan, Steven D.; Haggarty, Stephen J.] Harvard Univ, Dept Psychiat, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zhao, Wen-Ning; Tsai, Li-Huei; Haggarty, Stephen J.] Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Tsai, Li-Huei] MIT, Howard Hughes Med Inst, Picower Inst Learning & Memory, Cambridge, MA USA. RP Haggarty, SJ (reprint author), Harvard Univ, Sch Med, Ctr Human Genet Res, Dept Neurol, 185 Cambridge St, Boston, MA 02114 USA. EM haggarty@chgr.mgh.harvard.edu OI Haggarty, Stephen J./0000-0002-7872-168X FU National Institutes of Health (NIH) [R33MH087896, R01MH091115]; National Institute of Mental Health (NIMH); FRAXA Research Foundation; Marigold Foundation; Stanley Medical Research Institute FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The project described was supported by grant numbers R33MH087896 (SJH) and R01MH091115 (LHT) from the National Institutes of Health (NIH) and National Institute of Mental Health (NIMH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health. Funding support was also provided in part by the FRAXA Research Foundation and Marigold Foundation (SJH) and the Stanley Medical Research Institute (LHT, SJH). NR 30 TC 26 Z9 27 U1 2 U2 15 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0571 J9 J BIOMOL SCREEN JI J. Biomol. Screen PD OCT PY 2012 VL 17 IS 9 SI SI BP 1252 EP 1263 DI 10.1177/1087057112456876 PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry GA 014CG UT WOS:000309352100015 PM 22923789 ER PT J AU Nielson, CM Klein, RF Orwoll, ES AF Nielson, Carrie M. Klein, Robert F. Orwoll, Eric S. TI Sex and the single nucleotide polymorphism: Exploring the genetic causes of skeletal sex differences SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID BONE-MINERAL DENSITY; ESTROGEN-RECEPTOR-ALPHA; EXPRESSION; DIMORPHISM; GENDER; MASS; OSTEOPOROSIS; METAANALYSIS; OSTEOCLASTS; STRENGTH C1 [Klein, Robert F.; Orwoll, Eric S.] Oregon Hlth & Sci Univ, Dept Med, Bone & Mineral Unit, Portland, OR 97239 USA. [Klein, Robert F.] Portland VA Med Ctr, Portland, OR USA. RP Orwoll, ES (reprint author), Oregon Hlth & Sci Univ, Bone & Mineral Unit CR 113, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM orwoll@ohsu.edu OI Orwoll, Eric/0000-0002-8520-7355 FU NIAMS NIH HHS [K01 AR062655] NR 32 TC 1 Z9 2 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2012 VL 27 IS 10 BP 2047 EP 2050 DI 10.1002/jbmr.1723 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 007ZB UT WOS:000308925800002 PM 22991137 ER PT J AU Kim, SW Pajevic, PD Selig, M Barry, KJ Yang, JY Shin, CS Baek, WY Kim, JE Kronenberg, HM AF Kim, Sang Wan Pajevic, Paola Divieti Selig, Martin Barry, Kevin J. Yang, Jae-Yeon Shin, Chan Soo Baek, Wook-Young Kim, Jung-Eun Kronenberg, Henry M. TI Intermittent parathyroid hormone administration converts quiescent lining cells to active osteoblasts SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE OSTEOBLASTS; PTH; LINING CELLS; LINEAGE TRACING STUDY; INDUCIBLE TRANSGENE SYSTEM ID BONE-FORMATION; IN-VIVO; EXPRESSION; DIFFERENTIATION; RECEPTOR; RATS; PTH AB Intermittent administration of parathyroid hormone (PTH) increases bone mass, at least in part, by increasing the number of osteoblasts. One possible source of osteoblasts might be conversion of inactive lining cells to osteoblasts, and indirect evidence is consistent with this hypothesis. To better understand the possible effect of PTH on lining cell activation, a lineage tracing study was conducted using an inducible gene system. Dmp1-CreERt2 mice were crossed with ROSA26R reporter mice to render targeted mature osteoblasts and their descendents, lining cells and osteocytes, detectable by 5-bromo-4-chloro-3-indolyl-beta-d-galactopyranoside (X-gal) staining. Dmp1-CreERt2(+):ROSA26R mice were injected with 0.25 mg 4-OH-tamoxifen (4-OHTam) on postnatal days 3, 5, 7, 14, and 21. The animals were euthanized on postnatal day 23, 33, or 43 (2, 12, or 22 days after the last 4-OHTam injection). On day 43, mice were challenged with a subcutaneous injection of human PTH (134, 80?mu g/kg) or vehicle once daily for 3 days. By 22 days after the last 4-OHTam injection, most X-gal (+) cells on the periosteal surfaces of the calvaria and the tibia were flat. Moreover, bone formation rate and collagen I(a1) mRNA expression were decreased at day 43 compared to day 23. After 3 days of PTH injections, the thickness of X-gal (+) cells increased, as did their expression of osteocalcin and collagen I(a1) mRNA. Electron microscopy revealed X-galassociated chromogen particles in thin cells prior to PTH administration and in cuboidal cells following PTH administration. These data support the hypothesis that intermittent PTH treatment can increase osteoblast number by converting lining cells to mature osteoblasts in vivo. (c) 2012 American Society for Bone and Mineral Research. C1 [Kim, Sang Wan; Pajevic, Paola Divieti; Barry, Kevin J.; Kronenberg, Henry M.] Harvard Univ, Massachusetts Gen Hosp, Endocrine Unit, Sch Med, Boston, MA 02114 USA. [Kim, Sang Wan] Seoul Natl Univ, Boramae Hosp, Dept Internal Med, Seoul, South Korea. [Selig, Martin] Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Sch Med, Boston, MA 02114 USA. [Kim, Sang Wan; Yang, Jae-Yeon; Shin, Chan Soo] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea. [Baek, Wook-Young; Kim, Jung-Eun] Kyungpook Natl Univ, Sch Med, Dept Mol Med, Cell & Matrix Res Inst, Taegu, South Korea. RP Kronenberg, HM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Endocrine Unit, Sch Med, Thier 1101,50 Blossom St, Boston, MA 02114 USA. EM hkronenberg@partners.org RI Kim, Sang Wan/J-5399-2012; Shin, Chan Soo/I-7320-2012; OI Shin, Chan Soo/0000-0002-5829-4465; Kim, Sang Wan/0000-0001-9561-9110 FU NIH [DK11794, DK079161]; National Research Foundation of Korea (NRF); Korea government (MEST) [2010-0003236]; Seoul National University Hospital [2010-0420] FX This work was supported by NIH grants DK11794 and DK079161, by a National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2010-0003236), and by a grant from Seoul National University Hospital (No. 2010-0420). NR 24 TC 50 Z9 52 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 2012 VL 27 IS 10 BP 2075 EP 2084 DI 10.1002/jbmr.1665 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 007ZB UT WOS:000308925800005 PM 22623172 ER PT J AU Murphy, CM Linehan, EL Reyner, JC Musser, PH Taft, CT AF Murphy, Christopher M. Linehan, Erin L. Reyner, Jacqueline C. Musser, Peter H. Taft, Casey T. TI Moderators of Response to Motivational Interviewing for Partner-violent Men SO JOURNAL OF FAMILY VIOLENCE LA English DT Article DE Intimate partner violence; Perpetrators; Treatment; Motivational interviewing; Stages of change ID THERAPY OUTCOME RESEARCH; HOMEWORK COMPLIANCE; WORKING ALLIANCE; BATTERERS; VALIDATION; READINESS; CONFLICT; SCALES; TRIAL AB Careful attention to motivation for change may enhance the effects of interventions for partner-violent men. The present study tested predictions about differential response to a two-session motivational intake (MI) for partner-violent men, which was compared to a structured intake (SI) control. For those who were initially reluctant to change, MI produced greater forward movement in stage of change. For those who claimed to have already solved their problems with partner abuse, MI produced greater backward movement in stage of change and greater homework compliance in subsequent group cognitive-behavioral therapy (CBT). MI led to a stronger collaborative working alliance for those high in contemplation of change, and greater group session attendance for those with high trait anger. Contrary to hypotheses, analyses of post-CBT partner assault revealed a differentially greater benefit of MI for participants with lower levels of pretreatment contemplation and trait anger. The findings provide qualified support for the expectation that MI has the greatest beneficial effects on those who appear initially reluctant to change. C1 [Murphy, Christopher M.; Linehan, Erin L.; Reyner, Jacqueline C.; Musser, Peter H.] Univ Maryland Baltimore Cty, Dept Psychol, Baltimore, MD 21250 USA. [Taft, Casey T.] VA Boston Healthcare Syst, Boston, MA USA. [Taft, Casey T.] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Murphy, CM (reprint author), Univ Maryland Baltimore Cty, Dept Psychol, 1000 Hilltop Circle, Baltimore, MD 21250 USA. EM chmurphy@umbc.edu NR 42 TC 2 Z9 2 U1 2 U2 14 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7482 J9 J FAM VIOLENCE JI J. Fam. Violence PD OCT PY 2012 VL 27 IS 7 BP 671 EP 680 DI 10.1007/s10896-012-9460-2 PG 10 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 011YC UT WOS:000309201200006 ER PT J AU Smith, AK Lo, B AF Smith, Alexander K. Lo, Bernard TI The Problem with Actually Tattooing DNR across Your Chest SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID PREFERENCES C1 [Smith, Alexander K.] Univ Calif San Francisco, Div Geriatr, Dept Med, San Francisco, CA 94941 USA. [Smith, Alexander K.] San Francisco VA Med Ctr, San Francisco, CA USA. [Lo, Bernard] Greenwall Fdn, New York, NY USA. [Lo, Bernard] Univ Calif San Francisco, Div Gen Internal Med, Dept Med, San Francisco, CA 94941 USA. RP Smith, AK (reprint author), Univ Calif San Francisco, Div Geriatr, Dept Med, 4150 Clement St 181 G, San Francisco, CA 94941 USA. EM aksmith@ucsf.edu NR 7 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2012 VL 27 IS 10 BP 1238 EP 1239 DI 10.1007/s11606-012-2134-1 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 008PL UT WOS:000308968900004 PM 22810355 ER PT J AU Zhang, YT Gellad, WF Zhou, L Lin, YJ Lave, JR AF Zhang, Yuting Gellad, Walid F. Zhou, Lei Lin, Yi-Jen Lave, Judith R. TI Access to and Use of $4 Generic Programs in Medicare SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE Medicare; low-cost generic drugs; pharmaceuticals ID QUALITY AB Although four-dollar programs ($4 per 30-day supply for selected generic drugs) have become important options for seniors to obtain affordable medications, little is known about access to these programs and the characteristics of those who use them. We quantify access to $4 programs based on driving distance; evaluate factors affecting the program use and potential cost-savings associated with switching to $4 programs in Medicare. Observational study. US Medicare Part D data, 5% random sample, 2007 347,653 elderly beneficiaries without Medicaid coverage or low-income subsidies. We evaluated how use of $4 programs was affected by driving distance to the store and the beneficiary's demographic and socioeconomic status, insurance coverage, health status, comorbidities, and medication use. For those who did not use the $4 programs, we calculated potential savings from switching to $4 generics. Eighty percent of seniors in Medicare Part D filled prescriptions for generic drugs that were commonly available at $4 programs. Among them, only 16.3% filled drugs through $4 programs. Beneficiaries who lived in poor areas, had less insurance, more co-morbidities, and used more drugs and lived closer to $4 generic retail pharmacies, were more likely to use these programs. Blacks were less likely to use the program relative to Whites (15.0% vs. 16.4%; OR = 0.75, 95% CI 0.71-0.80). While 53.2% of nonusers would save by switching to $4 program after incorporating travelling costs, 58% of those who could save would have net annual out-of-pocket savings of less than $20. The take-up rate of $4 programs was low in 2007 among Medicare beneficiaries. As more stores offer $4 programs and increasing numbers of drugs become generic, more beneficiaries could potentially benefit, as could the Medicare program. C1 [Zhang, Yuting; Zhou, Lei; Lave, Judith R.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA 15261 USA. [Gellad, Walid F.] Univ Pittsburgh, Sch Med, Div Gen Med, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA. [Gellad, Walid F.] RAND Corp, Pittsburgh, PA USA. [Zhou, Lei] PharmaNet i3, Indianapolis, IN USA. [Lin, Yi-Jen] Univ Pittsburgh, Grad Sch Publ & Int Affairs, Pittsburgh, PA 15261 USA. RP Zhang, YT (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA 15261 USA. EM ytzhang@pitt.edu OI Zhang, Yuting/0000-0002-6460-6779 FU RAND-University of Pittsburgh Health Institute (RUPHI); University of Pittsburgh School of the Health Sciences; National Center for Research Resources, National Institutes of Health (NIH) [UL1 RR024153]; NIH Roadmap for Medical Research; NIMH [RC1 MH088510]; AHRQ [R01 HS018657]; Highmark Inc. FX The RAND University of Pittsburgh Health Institute and the Clinical and Translational Science Institute: Translating Research into Practice Program. This project was supported in part by the RAND-University of Pittsburgh Health Institute (RUPHI), a formal collaboration between the RAND Corporation, RAND Health, and the University of Pittsburgh School of the Health Sciences. This publication was made possible by grant UL1 RR024153 from the National Center for Research Resources, a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. During the study period, Dr. Zhang was also supported by NIMH RC1 MH088510 and AHRQ R01 HS018657.; Dr. Gellad has received an honorarium from Vindico Medical Education for preparation of a continuing medical education (CME) activity focused on improving medication adherence. Drs. Zhang and Lave were investigators for a contact (2008-2009) to evaluate the effects of high-deductible health plans funded by Highmark Inc., which sells Part D plans. NR 13 TC 13 Z9 13 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2012 VL 27 IS 10 BP 1251 EP 1257 DI 10.1007/s11606-012-1993-9 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 008PL UT WOS:000308968900009 PM 22311333 ER PT J AU Riess, H Kelley, JM Bailey, RW Dunn, EJ Phillips, M AF Riess, Helen Kelley, John M. Bailey, Robert W. Dunn, Emily J. Phillips, Margot TI Empathy Training for Resident Physicians: A Randomized Controlled Trial of a Neuroscience-Informed Curriculum SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE empathy; randomized controlled trial; communication skills; graduate medical education; patient-physician relationship ID COMMUNICATION-SKILLS; PATIENT SATISFACTION; MEDICAL-EDUCATION; NEURAL MECHANISMS; PROGRAM; DECLINE AB Physician empathy is an essential attribute of the patient-physician relationship and is associated with better outcomes, greater patient safety and fewer malpractice claims. We tested whether an innovative empathy training protocol grounded in neuroscience could improve physician empathy as rated by patients. Randomized controlled trial. We randomly assigned residents and fellows from surgery, medicine, anesthesiology, psychiatry, ophthalmology, and orthopedics (N = 99, 52% female, mean age 30.6 +/- 3.6) to receive standard post-graduate medical education or education augmented with three 60-minute empathy training modules. Patient ratings of physician empathy were assessed within one-month pre-training and between 1-2 months post-training with the use of the Consultation and Relational Empathy (CARE) measure. Each physician was rated by multiple patients (pre-mean = 4.6 +/- 3.1; post-mean 4.9 +/- 2.5), who were blinded to physician randomization. The primary outcome was change score on the patient-rated CARE. The empathy training group showed greater changes in patient-rated CARE scores than the control (difference 2.2; P = 0.04). Trained physicians also showed greater changes in knowledge of the neurobiology of empathy (difference 1.8; P < 0.001) and in ability to decode facial expressions of emotion (difference 1.9; P < 0.001). A brief intervention grounded in the neurobiology of empathy significantly improved physician empathy as rated by patients, suggesting that the quality of care in medicine could be improved by integrating the neuroscience of empathy into medical education. C1 [Riess, Helen] Harvard Univ, Massachusetts Gen Hosp, Empathy & Relat Sci Program, Sch Med,Dept Psychiat, Boston, MA 02114 USA. [Kelley, John M.] Endicott Coll, Beverly, MA USA. RP Riess, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Empathy & Relat Sci Program, Sch Med,Dept Psychiat, Wang ACC Suite 812, Boston, MA 02114 USA. EM HRiess@Partners.Org RI Dunn, Emily/J-2350-2014 OI Dunn, Emily/0000-0003-4057-4538 FU Arnold P. Gold Foundation; David Judah Fund; Josiah Macy, Jr. Foundation; Risk Management Foundation FX We are grateful to the following foundations for their generous support: The Arnold P. Gold Foundation, The David Judah Fund, The Josiah Macy, Jr. Foundation, and The Risk Management Foundation. The funding agencies played no role in the design and conduct of this study, including analysis and interpretation of data, and preparation, review, and approval of the manuscript. NR 41 TC 47 Z9 51 U1 3 U2 44 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2012 VL 27 IS 10 BP 1280 EP 1286 DI 10.1007/s11606-012-2063-z PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 008PL UT WOS:000308968900013 PM 22549298 ER PT J AU Lin, OS Kozarek, RA Gluck, M Jiranek, GC Koch, J Kowdley, KV Irani, S Nguyen, M Dominitz, JA AF Lin, Otto S. Kozarek, Richard A. Gluck, Michael Jiranek, Geoffrey C. Koch, Johannes Kowdley, Kris V. Irani, Shayan Nguyen, Matthew Dominitz, Jason A. TI Preference for Colonoscopy Versus Computerized Tomographic Colonography: A Systematic Review and Meta-analysis of Observational Studies SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Review DE colorectal cancer; adenoma; screening; colonoscopy; computerized tomographic colonography ID LIMITED BOWEL PREPARATION; CANCER SCREENING COMPLIANCE; PRIMARY-CARE PATIENTS; CT COLONOGRAPHY; COLORECTAL-CANCER; PATIENT ACCEPTANCE; CONVENTIONAL COLONOSCOPY; VIRTUAL COLONOSCOPY; MR COLONOGRAPHY; OPTICAL COLONOSCOPY AB In recent years, colorectal cancer (CRC) screening using computerized tomographic colonography (CTC) has attracted considerable attention. In order to better understand patient preferences for CTC versus colonoscopy, we performed a systematic review and meta-analysis of the available literature. Data sources included published studies, abstracts and book chapters, in any language, with publication dates from 1995 through February 2012, and with prospective or retrospective enrollment of diagnostic or screening patients who had undergone both procedures and explicit assessment of their preference for colonoscopy versus CTC. A predefined algorithm identified eligible studies using computer and hand searches performed by two independent investigators. We used a mixed effects model to pool preference differences (defined as the proportion of subjects who preferred CTC minus the proportion who preferred colonoscopy for each study). Twenty-three studies met inclusion criteria, totaling 5616 subjects. In 16 of these studies, patients preferred CTC over colonoscopy, while colonoscopy was preferred in three studies. Due to the high degree of heterogeneity, an overall pooled preference difference was not calculated. Stratified analysis revealed that studies published in radiology journals (preference difference 0.590 [95 % CI 0.485, 0.694]) seemed more likely than studies in gastroenterology (0.218 [-0.015-0.451]) or general medicine journals (-0.158 [-0.389-0.072]) to report preference for CTC (p < 0.001). Studies by radiology authors showed a trend towards stronger preference for CTC compared with studies by gastroenterology authors. Symptomatic patients expressed no preference, but screening patients preferred CTC. There was no difference in preferences between studies using "masked" and "unmasked" preference ascertainment methods. Three studies featuring limited bowel preparations for CTC reported marked preference for CTC. There was no evidence of publication bias, while cumulative and exclusion analysis did not show any temporal trend or dominant study. Limitations included data heterogeneity and preference ascertainment limitations. In conclusion, most included studies reported preference for CTC. On stratified analysis, screening patients preferred CTC while diagnostic patients showed no preference. Studies published in radiology journals showed significantly stronger preference for CTC compared with studies in gastroenterology or general medicine journals. C1 [Lin, Otto S.; Kozarek, Richard A.; Gluck, Michael; Jiranek, Geoffrey C.; Koch, Johannes; Kowdley, Kris V.; Irani, Shayan; Nguyen, Matthew] Virginia Mason Med Ctr, Gastroenterol Sect, Seattle, WA 98101 USA. [Dominitz, Jason A.] VA Puget Sound Hlth Care Syst, Div Gastroenterol, Seattle, WA USA. [Dominitz, Jason A.] Univ Washington, Seattle, WA 98195 USA. RP Lin, OS (reprint author), Virginia Mason Med Ctr, Gastroenterol Sect, 1100 9th Ave, Seattle, WA 98101 USA. EM otto.lin@vmmc.org OI Dominitz, Jason/0000-0002-8070-7086 FU Cumberland Pharmaceuticals FX None of the authors have any financial conflicts of interest to report, with the following exceptions: 1) A research grant from Cumberland Pharmaceuticals to Dr. Otto Lin, for a pilot study assessing the efficacy and safety of crystalline lactulose as a colonoscopy bowel preparation agent; 2) Consultancies for Epigenomics Inc. and Salix Pharmaceuticals for Dr. Jason Dominitz. NR 72 TC 17 Z9 18 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2012 VL 27 IS 10 BP 1349 EP 1360 DI 10.1007/s11606-012-2115-4 PG 12 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 008PL UT WOS:000308968900021 PM 22700393 ER PT J AU Elwyn, G Frosch, D Thomson, R Joseph-Williams, N Lloyd, A Kinnersley, P Cording, E Tomson, D Dodd, C Rollnick, S Edwards, A Barry, M AF Elwyn, Glyn Frosch, Dominick Thomson, Richard Joseph-Williams, Natalie Lloyd, Amy Kinnersley, Paul Cording, Emma Tomson, Dave Dodd, Carole Rollnick, Stephen Edwards, Adrian Barry, Michael TI Shared Decision Making: A Model for Clinical Practice SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE shared decision making; patient centered care ID PATIENT-CENTERED CARE; COMMUNICATION; PHYSICIAN; AID; ENCOUNTER; AUTONOMY; RISKS AB The principles of shared decision making are well documented but there is a lack of guidance about how to accomplish the approach in routine clinical practice. Our aim here is to translate existing conceptual descriptions into a three-step model that is practical, easy to remember, and can act as a guide to skill development. Achieving shared decision making depends on building a good relationship in the clinical encounter so that information is shared and patients are supported to deliberate and express their preferences and views during the decision making process. To accomplish these tasks, we propose a model of how to do shared decision making that is based on choice, option and decision talk. The model has three steps: a) introducing choice, b) describing options, often by integrating the use of patient decision support, and c) helping patients explore preferences and make decisions. This model rests on supporting a process of deliberation, and on understanding that decisions should be influenced by exploring and respecting "what matters most" to patients as individuals, and that this exploration in turn depends on them developing informed preferences. C1 [Elwyn, Glyn; Joseph-Williams, Natalie; Lloyd, Amy; Kinnersley, Paul; Cording, Emma; Rollnick, Stephen; Edwards, Adrian] Cardiff Univ, Cochrane Inst Primary Care & Publ Hlth, Cardiff CF14 4XN, S Glam, Wales. [Elwyn, Glyn] Dartmouth Coll, Dartmouth Ctr Hlth Care Delivery Sci, Hanover, NH 03755 USA. [Frosch, Dominick] Palo Alto Med Res Fdn, Res Inst, Dept Hlth Serv Res, Palo Alto, CA 94301 USA. [Frosch, Dominick] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Thomson, Richard] Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Tomson, Dave] New York Surg, Collingwood Hlth Grp, N Shields, England. [Dodd, Carole] Newcastle Upon Tyne Hosp NHS Fdn Trust, Clin Governance & Risk Dept, Newcastle Upon Tyne, Tyne & Wear, England. [Barry, Michael] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Barry, Michael] Informed Med Decis Fdn, Boston, MA USA. RP Elwyn, G (reprint author), Cardiff Univ, Cochrane Inst Primary Care & Publ Hlth, Heath Pk, Cardiff CF14 4XN, S Glam, Wales. EM glynelwyn@gmail.com RI Elwyn, G./L-4292-2015; OI Elwyn, Glyn/0000-0002-0917-6286 FU Health Foundation FX We acknowledge the Health Foundation, who commissioned work on shared decision making in the UK (Making Good Decisions in Collaboration: MAGIC), which provided the stimulus for this article. NR 50 TC 306 Z9 311 U1 7 U2 72 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2012 VL 27 IS 10 BP 1361 EP 1367 DI 10.1007/s11606-012-2077-6 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 008PL UT WOS:000308968900022 PM 22618581 ER PT J AU Pierce, JMR Estrada, CA Mathews, RE AF Pierce, J. Matthew R. Estrada, Carlos A. Mathews, Ronnie E., Jr. TI Buyers Beware: Lead Poisoning due to Ayurvedic Medicine SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE dietary supplements; lead; India; medicine; Ayurvedic; Phytotherapy; plant extracts/chemistry AB A 29-year-old man, who recently emigrated from India, presented with a 2-week history of abdominal pain, as well as nausea, constipation, and fatigue. He underwent removal of a parathyroid adenoma 6 weeks prior to admission and received a locally made Indian traditional medicine (Ayurveda) for pain control; however, this information was not initially available. He was instructed to take approximately 15 g/day. Initial evaluation revealed a normocytic anemia, but other workup including imaging and endoscopy was unrevealing. Given his recent use of Ayurvedic medicines, we tested for lead poisoning and found a blood lead level of 72 mcg/dl. We sent his medicine for analysis and found it had a high lead concentration of 36,000 mcg/g, which is over 25,000 times the maximum daily dose. He improved with cessation of the medicine and treatment with succimer. Lead poisoning can present with a variety of nonspecific signs and symptoms, including abdominal pain and anemia. Ayurvedic medicines, as well as traditional medicines from other cultures, may be a source of lead or other heavy metals. It is essential for physicians to be aware of adverse effects of Ayurvedic medicines as they are easily available and increasing in popularity. C1 [Estrada, Carlos A.] Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. [Estrada, Carlos A.] Vet Affairs Natl Qual Scholars Program, Birmingham, AL USA. RP Estrada, CA (reprint author), Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, FOT 732,510 20th St S, Birmingham, AL 35294 USA. EM cestrada@uab.edu NR 12 TC 1 Z9 1 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2012 VL 27 IS 10 BP 1384 EP 1386 DI 10.1007/s11606-012-2048-y PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 008PL UT WOS:000308968900026 PM 22476953 ER PT J AU Hoggatt, KJ Flores, M Solorio, R Wilhelm, M Ritz, B AF Hoggatt, Katherine J. Flores, Marie Solorio, Rosa Wilhelm, Michelle Ritz, Beate TI The "Latina Epidemiologic Paradox" Revisited: The Role of Birthplace and Acculturation in Predicting Infant Low Birth Weight for Latinas in Los Angeles, CA SO JOURNAL OF IMMIGRANT AND MINORITY HEALTH LA English DT Article DE Low birth weight; Latina, Hispanic; US-born, foreign-born; Acculturation; Two-phase analysis ID UNITED-STATES; PREGNANCY OUTCOMES; MORTALITY DIFFERENTIALS; MEXICAN-AMERICANS; PERINATAL HEALTH; PRETERM BIRTH; WOMEN; POPULATION; CALIFORNIA; ETHNICITY AB The "Latina epidemiologic paradox" refers to the observation that despite socioeconomic disadvantages, Latina mothers in the United States (US) have a similar or lower risk for delivering an infant with low birth weight (LBW) compared to non-Latina White mothers. An analogous paradox may exist between foreign-born (FB) and US-born (USB) Latinas. Our goal was to assess differences in LBW in USB Latinas, FB Latinas, and non-Latina Whites in Los Angeles County in 2003 using birth records and survey data. Using logistic regression, we estimated associations between LBW and birthplace/ethnicity in a birth cohort and nested survey responder group and between LBW and acculturation in responders to a follow-up survey. USB Latinas and FB Latinas had a higher prevalence of LBW infants compared to Whites (odds ratio [OR] = 1.34, 95% confidence interval [CI] = (1.17, 1.53) and OR = 1.32, 95% CI = (1.18, 1.49), respectively); when we adjusted for additional maternal risk factors these point estimates were attenuated, and interval estimates were consistent with a modest positive or inverse association. Among Latinas only, LBW was more common for high-acculturated FB and USB Latinas compared to low-acculturated FB Latinas, and there was limited evidence that environmental or behavior risk factors had less impact in low-acculturated Latinas. In summary, adjusting only for demographics, Latinas in our study were more likely to have LBW infants compared to Whites, in contrast to the Latina paradox hypothesis. Furthermore, adjusting for environmental or behavioral factors attenuated the positive association, but there was little evidence that Latinas had a lower prevalence of LBW regardless of the variables included in the models. Finally, among Latinas, there was limited evidence that associations between known risk factors and LBW were modified by acculturation. C1 [Hoggatt, Katherine J.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90095 USA. [Hoggatt, Katherine J.] VA Greater Los Angeles, HSR&D Ctr Excellence, Study Healthcare Provider Behav, Los Angeles, CA 91343 USA. [Flores, Marie] Univ Utah, Sch Med, Salt Lake City, UT USA. [Solorio, Rosa] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Wilhelm, Michelle; Ritz, Beate] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RP Hoggatt, KJ (reprint author), Univ Calif Los Angeles, Sch Publ Hlth, Box 951772, Los Angeles, CA 90095 USA. EM khoggatt@ucla.edu RI Ritz, Beate/E-3043-2015 FU NIEHS NIH HHS [5 P30 ES07048, P30 ES007048, R01 ES010960]; NINR NIH HHS [R21 NR010856] NR 40 TC 11 Z9 11 U1 0 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1912 J9 J IMMIGR MINOR HEALT JI J. Immigr. Minor. Health PD OCT PY 2012 VL 14 IS 5 BP 875 EP 884 DI 10.1007/s10903-011-9556-4 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 004BX UT WOS:000308656200019 PM 22160842 ER PT J AU Chou, SHY Feske, SK Atherton, J Konigsberg, RG De Jager, PL Du, R Ogilvy, CS Lo, EH Ning, MM AF Chou, Sherry H. -Y. Feske, Steven K. Atherton, Juli Konigsberg, Rachael G. De Jager, Philip L. Du, Rose Ogilvy, Christopher S. Lo, Eng H. Ning, MingMing TI Early Elevation of Serum Tumor Necrosis Factor-alpha Is Associated With Poor Outcome in Subarachnoid Hemorrhage SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article DE biomarker; subarachnoid hemorrhage; tumor necrosis factor alpha; inflammation ID BRAIN-INJURY; CEREBRAL VASOSPASM; ADHESION MOLECULES; CYTOKINES; INFLAMMATION; INTERLEUKIN-6; ISCHEMIA; CELL AB Objective: Subarachnoid hemorrhage (SAH) is associated with inflammation that may mediate poor outcome in SAH. We hypothesize that elevated serum tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) are associated with vasospasm and poor outcome in SAH. Methods: In 52 consecutive SAH subjects, we compared TNF-alpha and IL-6 levels on post-SAH days 0 to 1, 2 to 3, 4 to 5, 6 to 8, and 10 to 14 with respect to vasospasm and to poor outcome at 3 and 6 months. Vasospasm was defined as more than 50% reduction in vessel caliber on angiography. Poor outcome was defined as modified Rankin score greater than 2. Results: Elevated TNF-alpha on post-SAH days 2 to 3 was associated with poor 3-month outcome (P = 0.0004). Global elevation of TNF-alpha over time (post-SAH days 0-14) was independently associated with poor 3-month outcome after adjusting for Hunt-and-Hess grade and age (P = 0.02). Neither cross-sectional nor IL-6 levels over time were associated with outcome. Neither TNF-alpha nor IL-6 levels were associated with vasospasm. Conclusions: Elevation in serum TNF-alpha on post-SAH days 2 to 3 and global elevation of TNF-alpha over time are associated with poor outcome but not with angiographic vasospasm in this small cohort. Future studies are needed to define the role of TNF-alpha in SAH-related brain injury and its potential as a SAH outcome biomarker. C1 [Ogilvy, Christopher S.; Lo, Eng H.; Ning, MingMing] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. [Chou, Sherry H. -Y.; Feske, Steven K.; Konigsberg, Rachael G.; De Jager, Philip L.] Harvard Univ, Sch Med, Dept Neurol, Brigham & Womens Hosp, Boston, MA 02114 USA. [Atherton, Juli] Univ Quebec, Dept Math, Montreal, PQ H3C 3P8, Canada. [Du, Rose] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. RP Lo, EH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 15 Parkman St, Boston, MA 02114 USA. EM lo@helix.mgh.harvard.edu; ning@hms.harvard.edu RI Du, Rose/I-5402-2012; Chou, Sherry/G-5779-2015 OI Du, Rose/0000-0003-2641-6496; FU Department of Neurology, Brigham and Women's Hospital; American Heart Association [10CRP2610341]; Harvard Clinical Translational Research Center [5KL2RR025757]; American Federation for Medical Research (AFMR); United States National Institute of Health-National Institute of Neurological Disorders and Stroke [K23-NS073806, R37-NS37074, P01-NS55104, R21-NS52498, R01-NS48422] FX The authors thank Drs FA Sorond and GV Henderson (Department of Neurology, Brigham and Women's Hospital) for subject recruitment, Dr AH Ropper (Department of Neurology, Brigham and Women's Hospital) for advice and funding support, Dr Elizabeth Secor for statistical consultation, Dr JW Lee (Department of Neurology, Brigham and Women's Hospital) for editorial advice, and the Harvard Clinical Translational Science Center (Harvard Catalyst) for supporting biomarker analysis.; Supported by American Heart Association (10CRP2610341, Chou), Harvard Clinical Translational Research Center (5KL2RR025757, Chou), The American Federation for Medical Research (AFMR Scholar Award, Chou), and the United States National Institute of Health-National Institute of Neurological Disorders and Stroke (K23-NS073806, R37-NS37074, Lo; P01-NS55104, Lo; R21-NS52498, Ning; R01-NS48422, Ning). NR 19 TC 21 Z9 23 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD OCT PY 2012 VL 60 IS 7 BP 1054 EP 1058 PG 5 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 012FI UT WOS:000309220700017 PM 22918199 ER PT J AU Blagrove, M Fouquet, NC Baird, AL Pace-Schott, EF Davies, AC Neuschaffer, JL Henley-Einion, JA Weidemann, CT Thome, J McNamara, P Turnbull, OH AF Blagrove, Mark Fouquet, Nathalie C. Baird, Alison L. Pace-Schott, Edward F. Davies, Anna C. Neuschaffer, Jennifer L. Henley-Einion, Josephine A. Weidemann, Christoph T. Thome, Johannes McNamara, Patrick Turnbull, Oliver H. TI Association of salivary-assessed oxytocin and cortisol levels with time of night and sleep stage SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE Sleep; REM sleep; N2 sleep; Oxytocin; Cortisol; Emotional attachment; Behavioural attachment; Memory consolidation ID MEMORY CONSOLIDATION; REM-SLEEP; NEUROHYPOPHYSEAL HORMONES; SOCIAL-BEHAVIOR; SECRETION; HUMANS; PLASMA; PITUITARY; NEUROPEPTIDES; VASOPRESSIN AB There have been proposals for REM to have a function of emotional memory consolidation, and also for REM sleep to be involved in the promotion of attachment behaviour. The hormones cortisol and oxytocin, respectively, may be involved in these proposed REM sleep functions. However, there are conflicting reports on whether levels of cortisol differ between sleep stages when time since sleep onset (SSO) is controlled, and virtually no literature on whether levels of oxytocin differ between sleep stages. This study thus investigated the changes in levels of oxytocin (OT) and cortisol (CT) across the night, and whether these levels differ between REM and N2 sleep when time SSO is controlled. 20 participants (10 males, 10 females, mean age = 20.45, SD = 2.01) were awakened 10 min into REM and N2 sleep periods in the sleep laboratory and gave saliva samples which were assayed for OT and CT. Levels of OT were relatively constant across the night, whereas CT increased significantly. REM and N2 did not differ significantly neither for OT nor for CT. The study has implications for models of sleep-dependent memory consolidation that incorporate the late sleep increase in cortisol as a functional component of memory consolidation, and also for the medical diagnostic assaying of OT during sleep. C1 [Blagrove, Mark; Fouquet, Nathalie C.; Davies, Anna C.; Neuschaffer, Jennifer L.; Henley-Einion, Josephine A.; Weidemann, Christoph T.; Thome, Johannes] Swansea Univ, Dept Psychol, Coll Human & Hlth Sci, Swansea SA2 8PP, W Glam, Wales. [Baird, Alison L.] Kings Coll London, Inst Psychiat, London WC2R 2LS, England. [Pace-Schott, Edward F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Thome, Johannes] Univ Rostock, Dept Psychiat, Rostock, Germany. [McNamara, Patrick] Boston Univ, Boston, MA 02215 USA. [Turnbull, Oliver H.] Bangor Univ, Bangor, Gwynedd, Wales. RP Blagrove, M (reprint author), Swansea Univ, Dept Psychol, Coll Human & Hlth Sci, Swansea SA2 8PP, W Glam, Wales. EM m.t.blagrove@swansea.ac.uk RI Weidemann, Christoph/E-8857-2011; OI Weidemann, Christoph T./0000-0002-4280-2744 FU Wales Institute for Cognitive Neuroscience FX Study was funded by the Wales Institute for Cognitive Neuroscience. NR 65 TC 11 Z9 11 U1 1 U2 11 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PD OCT PY 2012 VL 119 IS 10 SI SI BP 1223 EP 1232 DI 10.1007/s00702-012-0880-1 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 011RS UT WOS:000309183200017 PM 22911329 ER PT J AU Korrapati, MC Shaner, BE Neely, BA Alge, JL Arthur, JM Schnellmann, RG AF Korrapati, Midhun C. Shaner, Brooke E. Neely, Benjamin A. Alge, Joseph L. Arthur, John M. Schnellmann, Rick G. TI Diabetes-Induced Renal Injury in Rats Is Attenuated by Suramin SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GELATINASE-ASSOCIATED LIPOCALIN; KAPPA-B ACTIVATION; TGF-BETA; OBSTRUCTIVE NEPHROPATHY; PROTEOMIC ANALYSIS; SIGNALING PATHWAY; STATISTICAL-MODEL; GENE-EXPRESSION; EARLY BIOMARKER; KIDNEY-DISEASE AB Progression of hyperglycemia-induced renal injury is a contributing factor for diabetic nephropathy (DN)-induced end-stage renal disease (ESRD), and development of novel therapeutic strategies that act early to prevent progression of DN and ESRD are important. We examined the efficacy and mechanism(s) of suramin on hyperglycemia-induced renal injury before development of overt histological damage. Two groups of male Sprague-Dawley rats received streptozotocin (STZ) and one group received saline. Three weeks later, one STZ group received suramin (10 mg/kg). All animals were euthanized 1 week later (4 weeks). Although there was a decrease in creatinine clearance between control and STZ +/- suramin rats, there was no difference in creatinine clearance between STZ rats +/- suramin intervention. Liquid chromatography-tandem mass spectroscopy-based analysis revealed increases in urinary proteins that are early indicators of DN (e.g., cystatin C, clusterin, cathepsin B, retinol binding protein 4, and peroxiredoxin-1) in the STZ group, which were blocked by suramin. Endothelial intracellular adhesion molecule-1 (ICAM-1) activation, leukocyte infiltration, and inflammation; transforming growth factor-beta 1 (TGF-beta 1) signaling; TGF-beta 1/SMAD-3-activated fibrogenic markers fibronectin-1, alpha-smooth muscle actin, and collagen 1A2; activation of proinflammatory and profibrotic transcription factors nuclear factor-kappa B (NF-kappa B) and signal transducer and activator of transcription factor-3 (STAT-3), respectively, were all increased in STZ rats and suramin blocked these changes. In conclusion, delayed administration of suramin attenuated 1) urinary markers of DN, 2) inflammation by blocking NF-kappa B activation and ICAM-1-mediated leukocyte infiltration, and 3) fibrosis by blocking STAT-3 and TGF-beta 1/SMAD-3 signaling. These results support the potential use of suramin in DN. C1 [Korrapati, Midhun C.; Shaner, Brooke E.; Schnellmann, Rick G.] Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Div Nephrol, Charleston, SC 29425 USA. [Neely, Benjamin A.; Alge, Joseph L.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Arthur, John M.; Schnellmann, Rick G.] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. RP Schnellmann, RG (reprint author), Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Div Nephrol, 280 Calhoun St,MSC140, Charleston, SC 29425 USA. EM schnell@musc.edu OI Neely, Benjamin/0000-0001-6120-7695; Alge, Joseph/0000-0002-2491-1066 FU National Institutes of Health National Institute of General Medical Sciences [GM084147]; National Institutes of Health National Center for Research Resources [UL1-RR029882, C06-RR015455]; Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs; South Carolina Clinical and Translational Research Institute; Medical University of South Carolina FX This work was supported by the National Institutes of Health National Institute of General Medical Sciences [Grant GM084147]; the National Institutes of Health National Center for Research Resources [Grant UL1-RR029882]; the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs; the South Carolina Clinical and Translational Research Institute, with an academic home at the Medical University of South Carolina. Animal facilities were funded by National Institutes of Health National Center for Research Resources [Grant C06-RR015455]. NR 61 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD OCT PY 2012 VL 343 IS 1 BP 34 EP 43 DI 10.1124/jpet.112.196964 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 009AK UT WOS:000308997500004 PM 22736507 ER PT J AU Sher, L Grunebaum, MF Sullivan, GM Burke, AK Cooper, TB Mann, JJ Oquendo, MA AF Sher, Leo Grunebaum, Michael F. Sullivan, Gregory M. Burke, Ainsley K. Cooper, Thomas B. Mann, J. John Oquendo, Maria A. TI Testosterone levels in suicide attempters with bipolar disorder SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Testosterone; Bipolar disorder; Depression; Suicide; Smoking ID GENDER-DIFFERENCES; PERSONALITY DIMENSIONS; AGGRESSIVE-BEHAVIOR; PLASMA TESTOSTERONE; DEPRESSED-PATIENTS; VIOLENT OFFENDERS; ADOLESCENT MALES; CONTROLLED-TRIAL; DOUBLE-BLIND; STEROID USE AB Objective: The best known neurobehavioral effects of testosterone are on sexual function and aggression. However, testosterone and other androgens may be involved in the pathophysiology of mood disorders and suicidal behavior. This is the first study to examine whether there is a relation between testosterone levels and clinical parameters in bipolar suicide attempters. Methods: Patients with a DSM-IV diagnosis of a bipolar disorder (16 males and 51 females), in a depressive or mixed episode with at least one past suicide attempt were enrolled. Demographic and clinical parameters, including lifetime suicidal behavior, were assessed and recorded. Plasma testosterone was assayed using a double antibody radioimmunoassay procedure. Results: The number of major depressive episodes, the maximum lethality of suicide attempts, and the testosterone levels were higher in men compared to women. Current suicidal ideation scores were higher in women compared to men. Controlling for sex, we found that testosterone levels positively correlated with the number of manic episodes and the number of suicide attempts. Conclusion: Our findings are consistent with previous observations of the association between testosterone levels and parameters of mood and behavior. This study suggests that testosterone levels may be related to the course of bipolar disorder and suicidal behavior. Further studies of the role of testosterone in the neurobiology of mood disorders and suicidal behavior are merited. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Sher, Leo] James J Peters Vet Adm Med Ctr, Bronx, NY 10468 USA. [Sher, Leo; Grunebaum, Michael F.; Sullivan, Gregory M.; Burke, Ainsley K.; Cooper, Thomas B.; Mann, J. John; Oquendo, Maria A.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Sher, Leo; Grunebaum, Michael F.; Sullivan, Gregory M.; Burke, Ainsley K.; Cooper, Thomas B.; Mann, J. John; Oquendo, Maria A.] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Sher, Leo] Mt Sinai Sch Med, New York, NY USA. RP Sher, L (reprint author), James J Peters Vet Adm Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Leo.Sher@mssm.edu FU NIH [R01 MH59710, P50 MH62185, R01 MH48514] FX This research study supported by grants R01 MH59710, P50 MH62185, and R01 MH48514 from the NIH. The NIH had no further role in study design; in the collection, analysis, and interpretation of the data; in the writing of the report; and in the decision to submit the paper for publication. NR 62 TC 18 Z9 19 U1 0 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD OCT PY 2012 VL 46 IS 10 BP 1267 EP 1271 DI 10.1016/j.jpsychires.2012.06.016 PG 5 WC Psychiatry SC Psychiatry GA 013GU UT WOS:000309294700003 PM 22858352 ER PT J AU Jahshan, C Wynn, JK Breitmeyer, BG Green, MF AF Jahshan, Carol Wynn, Jonathan K. Breitmeyer, Bruno G. Green, Michael F. TI Nonconscious and conscious color priming in schizophrenia SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE Schizophrenia; Visual processing; Color priming; Nonconscious; Feed forward ID PSYCHIATRIC RATING-SCALE; VISUAL BACKWARD-MASKING; PARVOCELLULAR CONTRIBUTIONS; CONTRAST SENSITIVITY; QUALITY-ASSURANCE; ATTENTION; FORM; DYSFUNCTION; POTENTIALS; TRANSIENT AB Deficits in visual processing are well established in schizophrenia. However, there is conflicting evidence about whether these deficits start before the formation of percepts because visual processing studies in schizophrenia have typically examined the processing of consciously registered stimuli. In this study, we used nonconscious color priming to evaluate the very early visual processing stages in schizophrenia. Nonconscious and conscious color priming was assessed in 148 schizophrenia patients and 54 healthy control subjects. In both conditions, subjects identified the color of a ring preceded by a disk (prime) in the same color (congruent) or a different color (incongruent). The ring rendered the disk invisible in the nonconscious condition (SOA of 62.5 ms) or did not mask the disk (SOA of 200 ms) in the conscious condition. Schizophrenia patients exhibited a color priming effect (longer reaction times in the incongruent vs. congruent trials) that was similar to healthy controls in both the nonconscious and conscious priming conditions. Healthy controls had a significantly larger priming effect in the nonconscious vs. conscious condition, but patients did not show a significant difference in priming effects between the two conditions. Our results indicate that schizophrenia patients do not have deficits at the nonconscious, pre-perceptual stages of visual processing, suggesting that the feed forward sweep of information processing (from retina to V1) might be intact in schizophrenia. These results imply that the welldocumented visual processing deficits in this illness likely occur at later, percept-dependent stages of processing. Published by Elsevier Ltd. C1 [Jahshan, Carol; Wynn, Jonathan K.; Green, Michael F.] VA Greater Los Angeles Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 22, Los Angeles, CA 90073 USA. [Wynn, Jonathan K.; Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Breitmeyer, Bruno G.] Univ Houston, Dept Psychol, Houston, TX USA. [Breitmeyer, Bruno G.] Univ Houston, Ctr Neuroengn & Cognit Sci, Houston, TX USA. RP Jahshan, C (reprint author), VA Greater Los Angeles Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 22, Bldg 210,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM caroljahshan@hotmail.com RI Wynn, Jonathan/H-3749-2014 OI Wynn, Jonathan/0000-0002-1763-8540 FU NIH [MH043292, MH065707] FX Funding for this study was provided by NIH Grants MH043292 and MH065707 (MFG). The NIH had no further role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 47 TC 8 Z9 10 U1 2 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIATR RES JI J. Psychiatr. Res. PD OCT PY 2012 VL 46 IS 10 BP 1312 EP 1317 DI 10.1016/j.jpsychires.2012.06.009 PG 6 WC Psychiatry SC Psychiatry GA 013GU UT WOS:000309294700010 PM 22785333 ER PT J AU Kimball, AB Wu, EQ Guerin, A Yu, AP Tsaneva, M Gupta, SR Bao, YJ Mulani, PM AF Kimball, Alexa B. Wu, Eric Q. Guerin, Annie Yu, Andrew P. Tsaneva, Magda Gupta, Shiraz R. Bao, Yanjun Mulani, Parvez M. TI Risks of developing psychiatric disorders in pediatric patients with psoriasis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE anxiety; comorbidity; depression; pediatrics; psoriasis; psychotropic medications ID DEPRESSION; CHILDHOOD; ALCOHOL; ADOLESCENTS; POPULATION; DISTRESS; ANXIETY; ACNE AB Background: Symptoms of psoriasis can be embarrassing and distressing, and may increase risk of developing psychiatric disorders in young people. Objective: We sought to compare incidences of psychiatric disorders between pediatric patients with psoriasis and psoriasis-free control subjects. Methods: Patients (<18 years) with continuous health plan enrollment 6 months before and after first psoriasis diagnosis (index date) were selected (Thomson Reuters MarketScan database, 2000-2006 [Thomson Reuters, New York, NY]). Patients with psoriasis (N = 7404) were matched 1: 5 on age and sex to psoriasis-free control subjects (N = 37,020). Patients were followed from index date to first diagnosis of a psychiatric disorder (ie, alcohol/drug abuse, depression, anxiety disorder, bipolar disorder, suicidal ideation, eating disorder), end of data availability, or disenrollment. Patients with psychiatric diagnoses or psychotropic medication use before the index date were excluded. Cox proportional hazard models controlling for age, sex, and comorbidities were used to estimate the effect of psoriasis on risks of developing psychiatric disorders. Results: Patients with psoriasis were significantly more at risk of developing psychiatric disorders versus control subjects (5.13% vs 4.07%; P=.0001; hazard ratio = 1.25; P=.0001), especially depression(3.01% vs 2.42%; P=.0036; hazard ratio = 1.25; P=.0053) and anxiety (1.81% vs 1.35%; P=.0048; hazard ratio = 1.32; P=.0045). Limitations: Retrospective, observational studies of medical claims data are typically limited by overall quality and completeness of data and accuracy of coding for diagnoses and procedures. Conclusions: Pediatric patients with psoriasis had an increased risk of developing psychiatric disorders, including depression and anxiety, compared with psoriasis-free control subjects. (J Am Acad Dermatol 2012;67:651-7.) C1 [Kimball, Alexa B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Kimball, Alexa B.] Harvard Univ, Clin Unit Res Trials Skin, Boston, MA 02114 USA. [Wu, Eric Q.; Guerin, Annie; Yu, Andrew P.; Tsaneva, Magda] Anal Grp Inc, Boston, MA USA. [Gupta, Shiraz R.; Bao, Yanjun; Mulani, Parvez M.] Abbott Labs, Abbott Pk, IL 60064 USA. RP Kimball, AB (reprint author), Harvard Univ, Massachusetts Gen & Brigham & Womens Hosp, Sch Med, 50 Staniford St,246, Boston, MA 02114 USA. EM harvardskinstudies@partners.org FU Abbott Laboratories; Abbott Park, IL; Centocor FX Funded in full by Abbott Laboratories, Abbott Park, IL. Data were analyzed by Analysis Group Inc. Medical writing and editing support was provided by Cathryn M. Carter, MS, of Arbor Communications Inc, Ann Arbor, MI. This support was funded by Abbott Laboratories, Abbott Park, IL.; Dr Kimball has served as investigator and consultant for Amgen, Centocor, and Abbott and has received grants from Centocor. Dr Wu, Ms Guerin, Dr Yu, and Ms Tsaneva are employees of Analysis Group Inc, under contract with Abbott Laboratories. Drs Gupta, Bao, and Mulani are employees of Abbott and hold stock in Abbott. NR 28 TC 29 Z9 29 U1 1 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD OCT PY 2012 VL 67 IS 4 BP 651 EP U263 DI 10.1016/j.jaad.2011.11.948 PG 9 WC Dermatology SC Dermatology GA 011JF UT WOS:000309160200047 PM 22243764 ER PT J AU Hawryluk, EB Sober, AJ Piris, A Nazarian, RM Hoang, MP Tsao, H Mihm, MC Duncan, LM AF Hawryluk, Elena B. Sober, Arthur J. Piris, Adriano Nazarian, Rosalynn M. Hoang, Mai P. Tsao, Hensin Mihm, Martin C., Jr. Duncan, Lyn M. TI Histologically challenging melanocytic tumors referred to a tertiary care pigmented lesion clinic SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE consensus; dermatopathology; melanocytic tumors; melanoma; pigmented lesions ID PRIMARY CUTANEOUS MELANOMA; AMERICAN JOINT COMMITTEE; MALIGNANT-MELANOMA; MITOTIC RATE; HISTOPATHOLOGIC DIAGNOSIS; OBSERVER VARIATION; DYSPLASTIC NEVI; INTEROBSERVER VARIABILITY; PROGNOSTIC-SIGNIFICANCE; PATHOLOGISTS AB Background: The histopathologic diagnosis of some melanocytic tumors is extraordinarily difficult. With this in mind, melanocytic tumors from patients referred to the Massachusetts General Hospital (MGH) Pigmented Lesion Clinic (PLC) are routinely reviewed in the MGH Dermatopathology Unit. Objective: We sought to determine the frequency of diagnostically challenging cases from patients treated at the MGH PLC, as measured by a change in the diagnosis upon review of the referral materials. Methods: We retrospectively reviewed the MGH and referral pathology reports for 478 consecutive cutaneous melanocytic tumors: 126 from 1996-1997 and 352 from 2010-2011. Differences in diagnosis and in therapeutic impact were evaluated. Results: Changes in diagnosis occurred in 168 of 478 cases (35%), more frequently when the original diagnostician was a general pathologist (P = .003). A similar fraction of diagnoses were changed from malignant to benign or vice versa, in both historic and contemporary cohorts. In 64 patients (13%), changes in diagnosis led to a change in therapy. Changes in stage or grading led to the most changes in therapy (78%; 50/64) versus changes from benign to malignant or vice versa (22%; 14/64). Limitations: This is a retrospective study with the bias of a tertiary-care referral center. Conclusions: These findings demonstrate the diagnostic difficulty of a subset of melanocytic tumors and highlight the utility of review by more than one pathologist; patient treatment is affected in more than 10% of cases. Identification of melanoma prognostic factors and melanocytic nevus grading led to clinically significant changes in diagnosis leading to a change in patient management. (J Am Acad Dermatol 2012;67:727-35.) C1 [Piris, Adriano; Nazarian, Rosalynn M.; Hoang, Mai P.; Duncan, Lyn M.] Massachusetts Gen Hosp, Dermatopathol Unit, Pathol Serv, Boston, MA 02114 USA. [Hawryluk, Elena B.; Sober, Arthur J.; Tsao, Hensin] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Mihm, Martin C., Jr.] Harvard Univ, Sch Med, Dept Dermatol, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Duncan, LM (reprint author), Massachusetts Gen Hosp, Dermatopathol Unit, Pathol Serv, 55 Fruit St,Warren 825, Boston, MA 02114 USA. EM duncan@helix.mgh.harvard.edu OI Nazarian, Rosalynn/0000-0003-4003-7193 NR 36 TC 6 Z9 6 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD OCT PY 2012 VL 67 IS 4 BP 727 EP 735 DI 10.1016/j.jaad.2012.02.036 PG 9 WC Dermatology SC Dermatology GA 011JF UT WOS:000309160200058 PM 22521204 ER PT J AU Alikhan, A Ibrahimi, OA Eisen, DB AF Alikhan, Ali Ibrahimi, Omar A. Eisen, Daniel B. TI Congenital melanocytic nevi: Where are we now? Part I. Clinical presentation, epidemiology, pathogenesis, histology, malignant transformation, and neurocutaneous melanosis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE congenital nevus; imaging; malignant melanoma; neurocutaneous melanosis; neuromelanosis; tethered spinal cord ID GIANT PIGMENTED NEVUS; DANDY-WALKER COMPLEX; NEUROLOGICALLY ASYMPTOMATIC CHILDREN; CEREBRIFORM INTRADERMAL NEVUS; INTERNET-BASED REGISTRY; FACTOR SCATTER FACTOR; ONE IDENTICAL TWIN; OF-THE-LITERATURE; CUTANEOUS MELANOMA; NEVOCYTIC NEVI AB Congenital melanocytic nevi (CMN) are present at birth or arise during the first few weeks of life. They are quite common, may have a heritable component, and can present with marked differences in size, shape, color, and location. Histologic and dermatoscopic findings may help suggest the diagnosis, but they are not entirely specific. CMN are categorized based on size, and larger lesions can have a significant psychosocial impact and other complications. They are associated with a variety of dermatologic lesions, ranging from benign to malignant. The risk of malignant transformation varies, with larger CMN carrying a significantly higher risk of malignant melanoma (MM), although with an absolute risk that is lower than is commonly believed. They may also be associated with neuromelanosis, which may be of greater concern than cutaneous MM. The information presented herein aims to help dermatologists determine when it is prudent to obtain a biopsy specimen or excise these lesions, to obtain radiographic imaging, and to involve other specialists (eg, psychiatrists and neurologists) in the patient's care. (J Am Acad Dermatol 2012;67:495.e1-17.) C1 [Eisen, Daniel B.] Univ Calif Davis, Sch Med, Dept Dermatol, Med Ctr, Sacramento, CA 95816 USA. [Alikhan, Ali] Mayo Clin, Dept Dermatol, Rochester, MN USA. [Ibrahimi, Omar A.] Univ Connecticut, Ctr Hlth, Dept Dermatol, Farmington, CT USA. [Ibrahimi, Omar A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed,Dept Dermatol, Boston, MA USA. RP Eisen, DB (reprint author), Univ Calif Davis, Sch Med, Dept Dermatol, Med Ctr, 3301 C St,Ste 1400, Sacramento, CA 95816 USA. EM dbeisen@ucdavis.edu OI Eisen, Daniel/0000-0001-6741-3182 NR 196 TC 1 Z9 1 U1 2 U2 12 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD OCT PY 2012 VL 67 IS 4 AR 495.e1 DI 10.1016/j.jaad.2012.06.023 PG 17 WC Dermatology SC Dermatology GA 011JF UT WOS:000309160200029 PM 22980258 ER PT J AU Ibrahimi, OA Alikhan, A Eisen, DB AF Ibrahimi, Omar A. Alikhan, Ali Eisen, Daniel B. TI Congenital melanocytic nevi: Where are we now? Part II. Treatment options and approach to treatment SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID Q-SWITCHED RUBY; GIANT PIGMENTED NEVI; OF-THE-LITERATURE; ERBIUM-YAG LASER; SELECTIVE PHOTOTHERMOLYSIS; NEVOMELANOCYTIC-NEVI; SERIAL EXCISION; MELANOMA-CELLS; ALEXANDRITE-LASERS; PULSED RADIATION AB Treatment of congenital melanocytic nevi (CMN) is generally undertaken for 2 reasons: (1) to reduce the chances of cutaneous malignant melanoma and (2) for cosmetic reasons. Over the past century, a large number of treatments for CMN have been described in the literature. These include excision, dermabrasion, curettage, chemical peels, radiation therapy, cryotherapy, electrosurgery, and lasers. Only low-level evidence supporting these approaches is available, and large randomized controlled trials have not been published. This article explores therapeutic controversies and makes recommendations based on the best available evidence. (J Am Acad Dermatol 2012;67:515.e1-13.) C1 [Eisen, Daniel B.] Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. [Ibrahimi, Omar A.] Univ Connecticut, Ctr Hlth, Dept Dermatol, Farmington, CT USA. [Ibrahimi, Omar A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Alikhan, Ali] Mayo Clin, Dept Dermatol, Rochester, MN USA. RP Eisen, DB (reprint author), Univ Calif Davis, Sch Med, Dept Dermatol, 3301 C St,Ste 1400, Sacramento, CA 95816 USA. EM dbeisen@ucdavis.edu OI Eisen, Daniel/0000-0001-6741-3182 NR 87 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD OCT PY 2012 VL 67 IS 4 AR 515.e1 DI 10.1016/j.jaad.2012.06.022 PG 13 WC Dermatology SC Dermatology GA 011JF UT WOS:000309160200030 PM 22980259 ER PT J AU Braunwald, E Sabatine, MS AF Braunwald, Eugene Sabatine, Marc S. TI The Thrombolysis in Myocardial Infarction (TIMI) Study Group experience SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID ACUTE CORONARY SYNDROMES; RANDOMIZED CONTROLLED-TRIAL; ORAL ANTIPLATELET THERAPY; ST-SEGMENT-ELEVATION; DIABETES-MELLITUS; TROPONIN-I; CONSERVATIVE STRATEGIES; NATRIURETIC PEPTIDE; ISCHEMIC EVENTS; UNSTABLE ANGINA AB The Thrombolysis in Myocardial Infarction (TIMI) study group, an academic research organization, was formed in 1984 with initial support from the National Heart, Lung, and Blood Institute. Its initial goal was to compare the effects of the then-new thrombolytic agent, recombinant tissue plasminogen activator, with streptokinase. The TIMI study group has remained active since then and has completed 50 multicenter clinical trials. The TIMI network now collaborates with more than 1000 separate sites in 45 countries on 5 continents. In addition to thrombolytic agents, TIMI has studied antithrombotic, antiplatelet, anti-ischemic, lipid lowering, and anti-inflammatory drugs. TIMI has also established robust biomarker and pharmacogenetics programs, and has devised a panel of risk assessment scores that are widely used. TIMI is currently conducting 7 large trials worldwide on novel agents designed to reduce the morbidity and mortality of a variety of cardiovascular disorders. (J Thorac Cardiovasc Surg 2012; 144: 762-70) C1 [Braunwald, Eugene] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Braunwald, E (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA. EM ebraunwald@partners.org RI bashzar, salman/R-5748-2016 FU Abbott; Astra Zeneca; Amgen; Bayer Healthcare; Bristol Myers Squibb; Daiichi Sanko; Eli Lilly; GlaxoSmithKline; Merck (SPRI); Pfizer; Roche (Diagnostics); Sanofi Aventis; Johnson Johnson FX The TIMI Study Group has received research grants from Abbott, Astra Zeneca, Amgen, Bayer Healthcare, Bristol Myers Squibb, Daiichi Sanko, Eli Lilly, GlaxoSmithKline, Merck (SPRI), Pfizer, Roche (Diagnostics), Sanofi Aventis, and Johnson & Johnson. NR 42 TC 5 Z9 5 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD OCT PY 2012 VL 144 IS 4 BP 762 EP 770 DI 10.1016/j.jtcvs.2012.07.001 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 010RK UT WOS:000309111600008 PM 22901500 ER PT J AU Thomas, M Li, Z Cook, DJ Greason, KL Sundt, TM AF Thomas, Mathew Li, Zhuo Cook, David J. Greason, Kevin L. Sundt, Thoralf M. TI Contemporary results of open aortic arch surgery SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID HYPOTHERMIC CIRCULATORY ARREST; SELECTIVE CEREBRAL PERFUSION; HIGH-RISK PATIENTS; ONE-STAGE REPAIR; BRAIN TEMPERATURE; HYBRID PROCEDURES; REPLACEMENT; ANEURYSMS; PRESERVATION; DYSFUNCTION AB Objectives: The success of endovascular therapies for descending thoracic aortic disease has turned attention toward stent graft options for repair of aortic arch aneurysms. Defining the role of such techniques demands understanding of contemporary results of open surgery. Methods: The outcomes of open arch procedures performed on a single surgical service from July 1, 2001 to August 30, 2010, were examined as defined per The Society of Thoracic Surgeons national database. Results: During the study period, 209 patients (median age, 65 years; range, 26-88) underwent arch operations, of which 159 were elective procedures. In 65 the entire arch was replaced, 22 of whom had portions of the descending thoracic aorta simultaneously replaced via bilateral thoracosternotomy. Antegrade cerebral perfusion was used in 78 patients and retrograde cerebral perfusion in 1. Operative mortality was 2.5% in elective circumstances and 10% in emergency cases (P = .04). The stroke rate was 5.0% when procedures were performed electively and 11.8% when on an emergency basis (P = .11). Procedure-specific mortality rates were 5.5% for elective and 10% for emergency procedures with total arch replacement, and 1.0% for elective and 10% for emergency procedures with hemiarch replacement. Stratified by extent, neurologic event rates were 5.5% for elective and 10% for emergency procedures with total arch and 4.8% for elective and 12.5% for emergency procedures with hemiarch replacement. Conclusions: Open aortic arch replacement can be performed with low operative mortality and stroke rates, especially in elective circumstances, by a team with particular focus on the procedure. The results of novel endovascular therapies should be benchmarked against contemporary open series performed in such a setting. (J Thorac Cardiovasc Surg 2012; 144: 838-44) C1 [Sundt, Thoralf M.] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. [Thomas, Mathew; Li, Zhuo; Greason, Kevin L.] Mayo Clin, Div Cardiovasc Surg, Rochester, MN USA. [Cook, David J.] Mayo Clin, Div Cardiovasc Anesthesia, Rochester, MN USA. RP Sundt, TM (reprint author), Massachusetts Gen Hosp, Div Cardiac Surg, 55 Fruit St,Cox 652, Boston, MA 02114 USA. EM tsundt@partners.org NR 42 TC 16 Z9 16 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD OCT PY 2012 VL 144 IS 4 BP 838 EP 844 DI 10.1016/j.jtcvs.2011.09.069 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 010RK UT WOS:000309111600017 PM 22177097 ER PT J AU Brasky, TM Baik, CS Slatore, CG Alvarado, M White, E AF Brasky, Theodore M. Baik, Christina S. Slatore, Christopher G. Alvarado, Mariela White, Emily TI Prediagnostic Nonsteroidal Anti-Inflammatory Drug Use and Lung Cancer Survival in the VITAL Study SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Aspirin; Ibuprofen; Nonsteroidal anti-inflammatory drugs; Lung Cancer; Histology; Survival ID C-REACTIVE PROTEIN; LOW-DOSE ASPIRIN; COLORECTAL-CANCER; WOMENS HEALTH; LARGE COHORT; RISK; TRIAL; INFLAMMATION; CELECOXIB; CHEMOTHERAPY AB Introduction: Inflammation is important for lung oncogenesis. Use of nonsteroidal anti-inflammatory drugs (NSAIDs) has been shown to improve colorectal cancer survival. However, few studies have examined the association in lung cancer patients. Methods: The VITamins And Lifestyle (VITAL) cohort includes Washington State residents, aged 50 to 76 years, who completed a baseline questionnaire between 2000 and 2002. Participants responded on the frequency and duration of use of individual NSAIDs in the previous 10 years. Subjects of this study were 785 members of the cohort, who were identified with incident lung cancer from baseline through 2007 through linkage to a population-based cancer registry. Participants were followed for lung cancer death through linkage to state records of death through 2009. Adjusted proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association between NSAIDs and lung cancer death. Results: Five hundred and twenty-two participants (66%) died from lung cancer. Relative to nonuse, high (>= 4 days/week and >= 4 years) prediagnostic use of regular-strength or low-dose aspirin (HR 0.99, 95% CI: 0.74-1.33 and HR 0.89, 95% CI: 0.67-1.17, respectively) or total nonaspirin NSAIDs (HR 1.20, 95% CI: 0.79-1.83) did not reduce lung cancer death. However, high use of ibuprofen was associated with a 62% increased risk of lung cancer death (HR 1.62, 95% CI: 1.01-2.58). Conclusions: Long-term, prediagnostic NSAID use does not improve lung cancer survival overall. Use of ibuprofen may reduce survival from lung cancer. Our results underscore the need for further study of the mechanisms of action for individual NSAIDs with regard to cancer survival. C1 [Brasky, Theodore M.] Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med, Div Canc Prevent & Control,Coll Med, Columbus, OH 43201 USA. [Brasky, Theodore M.; Baik, Christina S.; White, Emily] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. [Slatore, Christopher G.] Portland VA Med Ctr, Portland, OR USA. [Slatore, Christopher G.] Oregon Hlth & Sci Univ, Div Pulm & Crit Care Med, Portland, OR 97201 USA. [Alvarado, Mariela] Bastyr Univ, Dept Nat Med, Kenmore, WA USA. RP Brasky, TM (reprint author), Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med, Div Canc Prevent & Control,Coll Med, 1590 N High St,Suite 525, Columbus, OH 43201 USA. EM theodore.brasky@osumc.edu OI Slatore, Christopher/0000-0003-0958-8122 FU National Institutes of Health [R25-CA094880, K05-CA154337]; VA HSRD Career Development Award FX This work was supported by National Institutes of Health grants R25-CA094880 (National Cancer Institute) and K05-CA154337 (National Cancer Institute and Office of Dietary Supplements). Dr. Slatore is a recipient of a VA HSRD Career Development Award and is supported by resources from the Portland VA Medical Center. The Department of Veterans Affairs did not have a role in the conduct of the study, in the collection, management, analysis, or interpretation of data, or in the preparation of the article. 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 US Government. NR 39 TC 6 Z9 6 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD OCT PY 2012 VL 7 IS 10 BP 1503 EP 1512 DI 10.1097/JTO.0b013e3182641bdc PG 10 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 007WP UT WOS:000308919400010 PM 22982651 ER PT J AU Wakelee, HA Lee, JW Hanna, NH Traynor, AM Carbone, DP Schiller, JH AF Wakelee, Heather A. Lee, Ju-Whei Hanna, Nasser H. Traynor, Anne M. Carbone, David P. Schiller, Joan H. TI A Double-Blind Randomized Discontinuation Phase-II Study of Sorafenib (BAY 43-9006) in Previously Treated Non-Small-Cell Lung Cancer Patients Eastern Cooperative Oncology Group Study E2501 SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Non-small-cell lung cancer; Sorafenib; Randomized discontinuation trial ID REFRACTORY SOLID TUMORS; FACTOR RECEPTOR INHIBITOR; RAF KINASE; HEPATOCELLULAR-CARCINOMA; ANTITUMOR-ACTIVITY; TRIAL; BAY-43-9006; ERLOTINIB; MUTATIONS; THERAPY AB Introduction: Sorafenib is a raf kinase and angiogenesis inhibitor with activity in multiple cancers. This phase-II study in heavily pretreated non-small-cell lung cancer (NSCLC) patients (>= 2 prior therapies) used a randomized discontinuation design. Methods: Patients received 400 mg of sorafenib orally twice daily for two cycles (2 months) (step 1). Responding patients on step 1 continued on sorafenib; progressing patients went off study, and patients with stable disease were randomized to placebo or sorafenib (step 2), with crossover from placebo allowed upon progression. The primary endpoint of this study was the proportion of patients having stable or responding disease 2 months after randomization. Results: There were 299 patients evaluated for step 1; of these, 81 eligible patients were randomized on step 2 and received sorafenib (n = 50) or placebo (n = 31). The 2-month disease control rates after randomization were 54% and 23% for patients initially receiving sorafenib and placebo, respectively, p = 0.005. The hazard ratio for progression on step 2 was 0.51 (95% [confidence interval] CI 0.30, 0.87, p = 0.014) favoring sorafenib. A trend in favor of overall survival with sorafenib was also observed (13.7 versus 9.0 months from time of randomization), hazard ratio 0.67 (95% CI 0.40-1.11), p = 0.117. A dispensing error occurred, which resulted in the unblinding of some patients, but not before completion of the 8-week initial step 2 therapy. Toxicities were manageable and as expected. Conclusions: The results of this randomized discontinuation trial suggest that sorafenib has single-agent activity in a heavily pretreated, enriched patient population with advanced NSCLC. These results support further investigation with sorafenib as a single agent in larger, randomized studies in NSCLC. C1 [Wakelee, Heather A.] Stanford Univ, Stanford Canc Inst, Dept Med, Div Oncol, Stanford, CA 94305 USA. [Lee, Ju-Whei] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Hanna, Nasser H.] Indiana Univ Canc Ctr, Dept Med, Div Hematol Oncol, Indianapolis, IN USA. [Traynor, Anne M.] Univ Wisconsin, Dept Med, Div Med Oncol, Madison, WI USA. [Carbone, David P.] Vanderbilt Univ, Dept Med, Div Oncol, Nashville, TN USA. [Schiller, Joan H.] Univ Texas SW Med Ctr Dallas, Simmons Comprehens Canc Ctr, Dept Med, Div Hematol & Oncol, Dallas, TX 75390 USA. RP Wakelee, HA (reprint author), Stanford Univ, Stanford Canc Inst, Dept Med, Div Oncol, 875 Blake Wilbur Dr, Stanford, CA 94305 USA. EM hwakelee@stanford.edu FU Public Health Service [CA23318, CA66636, CA21115, CA49883, CA21076, CA49957]; National Cancer Institute, National Institutes of Health; Department of Health and Human Services FX This study was conducted by the Eastern Cooperative Oncology Group (Robert L. Comis, M. D., Chair) and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA49883, CA21076, and CA49957 and grants from the National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 31 TC 29 Z9 30 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD OCT PY 2012 VL 7 IS 10 BP 1574 EP 1582 DI 10.1097/JTO.0b013e31826149ba PG 9 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 007WP UT WOS:000308919400020 PM 22982658 ER PT J AU Foo, J Chmielecki, J Pao, W Michor, F AF Foo, Jasmine Chmielecki, Juliann Pao, William Michor, Franziska TI Effects of Pharmacokinetic Processes and Varied Dosing Schedules on the Dynamics of Acquired Resistance to Erlotinib in EGFR-Mutant Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE EGFR-mutant lung cancer; Erlotinib; Evolutionary cancer modeling; Pharmacokinetic modeling; Acquired resistance; EGFR T790M mutation ID CHRONIC MYELOID-LEUKEMIA; TYROSINE KINASE; GEFITINIB; MUTATION; SENSITIVITY; INHIBITOR; THERAPY; MODELS AB Introduction: Erlotinib (Tarceva) is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, which effectively targets EGFR-mutant driven non-small-cell lung cancer. However, the evolution of acquired resistance because of a second-site mutation (T790M) within EGFR remains an obstacle to successful treatment. Methods: We used mathematical modeling and available clinical trial data to predict how different pharmacokinetic parameters (fast versus slow metabolism) and dosing schedules (low dose versus high dose; missed doses with and without make-up doses) might affect the evolution of T790M-mediated resistance in mixed populations of tumor cells. Results: We found that high-dose pulses with low-dose continuous therapy impede the development of resistance to the maximum extent, both pre- and post-emergence of resistance. The probability of resistance is greater in fast versus slow drug metabolizers, suggesting a potential mechanism, unappreciated to date, influencing acquired resistance in patients. In case of required dose modifications because of toxicity, little difference is observed in terms of efficacy and resistance dynamics between the standard daily dose (150 mg/d) and 150 mg/d alternating with 100 mg/d. Missed doses are expected to lead to resistance faster, even if make-up doses are attempted. Conclusions: For existing and new kinase inhibitors, this novel framework can be used to rationally and rapidly design optimal dosing strategies to minimize the development of acquired resistance. C1 [Michor, Franziska] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Foo, Jasmine] Univ Minnesota, Sch Math, Minneapolis, MN 55455 USA. [Foo, Jasmine] Mason Canc Ctr, Minneapolis, MN USA. [Chmielecki, Juliann] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Pao, William] Vanderbilt Univ, Dept Med, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. RP Michor, F (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave, Boston, MA 02115 USA. EM william.pao@vanderbilt.edu; michor@jimmy.harvard.edu FU National Institutes of Health/National Cancer Institute [R01-CA121210, P01-CA129243]; Dana-Farber Cancer Institute Physical Sciences-Oncology Center [U54-CA143798]; Vanderbilt-Ingram Cancer Center Core grant [P30-CA68485] FX The authors acknowledge support from the National Institutes of Health/National Cancer Institute grants R01-CA121210 (William Pao), P01-CA129243 (William Pao), and the Dana-Farber Cancer Institute Physical Sciences-Oncology Center U54-CA143798 (Jasmine Foo, William Pao, and Franziska Michor). William Pao also received additional support from the Vanderbilt-Ingram Cancer Center Core grant (P30-CA68485). NR 24 TC 33 Z9 34 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD OCT PY 2012 VL 7 IS 10 BP 1583 EP 1593 DI 10.1097/JTO.0b013e31826146ee PG 11 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 007WP UT WOS:000308919400021 PM 22982659 ER PT J AU Papadimitrakopoulou, VA Soria, JC Jappe, A Jehl, V Klimovsky, J Johnson, BE AF Papadimitrakopoulou, Vassiliki A. Soria, Jean-Charles Jappe, Annette Jehl, Valentine Klimovsky, Judith Johnson, Bruce E. TI Everolimus and Erlotinib as Second- or Third-Line Therapy in Patients with Advanced Non-Small-Cell Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Dose-limiting toxicity; Erlotinib; Everolimus; Non-small-cell lung cancer; Phase I ID RAPAMYCIN INHIBITOR EVEROLIMUS; CLINICAL-PRACTICE GUIDELINES; ADVANCED SOLID TUMORS; MAMMALIAN TARGET; EGFR INHIBITORS; FOLLOW-UP; GEFITINIB; TRIAL; CHEMOTHERAPY; STAGE AB Introduction: The epidermal growth factor receptor inhibitor erlotinib is an approved treatment for chemotherapy-refractory advanced non-small-cell lung cancer (NSCLC). Because activated epidermal growth factor receptor signals through the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (mTOR) pathway, adding the oral mTOR inhibitor everolimus to erlotinib may improve efficacy by blocking multiple components of the same pathway. We conducted a phase I study to determine feasible dosages of combination therapy with erlotinib and everolimus for previously treated metastatic or unresectable NSCLC. Methods: Participants had advanced NSCLC progressing after two or less previous chemotherapy regimens. Feasibility of daily/weekly everolimus plus daily erlotinib was determined using a 6 + 6 dose-escalation design based on the rate of dose-limiting toxicities. Antitumor activity was assessed by the Response Evaluation Criteria In Solid Tumors study. Results: Of the 94 patients enrolled, 90% had stage IV NSCLC, 19% never smoked, and 15% were current smokers. Eighty-nine patients experienced one or more adverse events possibly related to any study medication. The most common dose-limiting toxicities were stomatitis (n = 5), rash (n = 4), and diarrhea (n = 3). Maximum tolerated doses were everolimus 5 mg per day or 50 mg per week plus erlotinib 150 mg per day. In daily everolimus cohorts (n = 74), nine patients achieved a complete/partial response and 28 had stable disease (median duration disease control, 9.3 months). In weekly everolimus cohorts (n = 20), no tumor response was observed; seven patients had stable disease (median duration, 9.6 months). Conclusions: Combination therapy with everolimus 5 mg per day or 50 mg per week and erlotinib 150 mg per day provided acceptable tolerability and disease control. A randomized phase II study evaluating this combination in comparison with erlotinib alone is complete and is being analyzed. C1 [Papadimitrakopoulou, Vassiliki A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Soria, Jean-Charles] Inst Gustave Roussy, Villejuif, France. [Soria, Jean-Charles] Univ Paris 11, Villejuif, France. [Jappe, Annette; Jehl, Valentine; Klimovsky, Judith] Novartis Pharmaceut, Basel, Switzerland. [Jappe, Annette; Jehl, Valentine; Klimovsky, Judith] Novartis Pharmaceut, Florham Pk, NJ USA. [Johnson, Bruce E.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Papadimitrakopoulou, VA (reprint author), Univ Texas MD Anderson Canc Ctr, 1515 Holcombe Blvd,Box 432, Houston, TX 77030 USA. EM vpapadim@mdanderson.org FU Novartis Pharmaceuticals Corporation FX This study was supported by Novartis Pharmaceuticals Corporation. NR 31 TC 16 Z9 16 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD OCT PY 2012 VL 7 IS 10 BP 1594 EP 1601 DI 10.1097/JTO.0b013e3182614835 PG 8 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 007WP UT WOS:000308919400022 PM 22968184 ER PT J AU Goldberg, SB Supko, JG Neal, JW Muzikansky, A Digumarthy, S Fidias, P Temel, JS Heist, RS Shaw, AT McCarthy, PO Lynch, TJ Sharma, S Settleman, JE Sequist, LV AF Goldberg, Sarah B. Supko, Jeffrey G. Neal, Joel W. Muzikansky, Alona Digumarthy, Subba Fidias, Panos Temel, Jennifer S. Heist, Rebecca S. Shaw, Alice T. McCarthy, Patricia O. Lynch, Thomas J. Sharma, Sreenath Settleman, Jeffrey E. Sequist, Lecia V. TI A Phase I Study of Erlotinib and Hydroxychloroquine in Advanced Non-Small-Cell Lung Cancer SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE Non-small-cell lung cancer; Erlotinib; Hydroxychloroquine ID GLIOBLASTOMA-MULTIFORME; RHEUMATOID-ARTHRITIS; DOUBLE-BLIND; GEFITINIB; AUTOPHAGY; RECEPTOR; GROWTH; ADENOCARCINOMA; CHLOROQUINE; RETREATMENT AB Introduction: This investigator-initiated study explores the safety, maximum tolerated dose, clinical response, and pharmacokinetics of hydroxychloroquine (HCQ) with and without erlotinib in patients with advanced non-small-cell lung cancer. Methods: Patients with prior clinical benefit from an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor were randomized to HCQ or HCQ plus erlotinib in a 3 + 3 dose-escalation schema. Results: Twenty-seven patients were treated, eight with HCQ (arm A) and 19 with HCQ plus erlotinib (arm B). EGFR mutations were detected in 74% of the patients and 85% had received two or more prior therapies. Arm A had no dose-limiting toxicities, but the maximum tolerated dose was not reached as this arm closed early to increase overall study accrual. In arm B, one patient each experienced grade 3 rash, nail changes, skin changes, nausea, dehydration, and neutropenia; one had grade 4 anemia; and one developed fatal pneumonitis, all considered unrelated to HCQ. There were no dose-limiting toxicities, therefore the highest tested dose for HCQ with erlotinib 150 mg was 1000 mg daily. One patient had a partial response to erlotinib/HCQ, for an overall response rate of 5% (95% confidence interval, 1-25). This patient had an EGFR mutation and remained on therapy for 20 months. Administration of HCQ did not alter the pharmacokinetics of erlotinib. Conclusions: HCQ with or without erlotinib was safe and well tolerated. The recommended phase 2 dose of HCQ was 1000 mg when given in combination with erlotinib 150 mg. C1 [Goldberg, Sarah B.; Supko, Jeffrey G.; Fidias, Panos; Temel, Jennifer S.; Heist, Rebecca S.; Shaw, Alice T.; McCarthy, Patricia O.; Settleman, Jeffrey E.; Sequist, Lecia V.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Goldberg, Sarah B.; Supko, Jeffrey G.; Muzikansky, Alona; Digumarthy, Subba; Fidias, Panos; Temel, Jennifer S.; Heist, Rebecca S.; Shaw, Alice T.; McCarthy, Patricia O.; Sequist, Lecia V.] Harvard Univ, Sch Med, Boston, MA USA. [Muzikansky, Alona] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Digumarthy, Subba] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Neal, Joel W.] Stanford Canc Inst, Stanford, CA USA. [Lynch, Thomas J.] Yale Univ, Sch Med, New Haven, CT USA. [Lynch, Thomas J.] Yale Canc Ctr, New Haven, CT USA. [Sharma, Sreenath] Novartis Inst Biomed Res, Cambridge, MA USA. [Settleman, Jeffrey E.] Genentech Inc, Dept Discovery Oncol, San Francisco, CA 94080 USA. RP Sequist, LV (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Profess Off Bldg,Room 212, Boston, MA 02114 USA. EM lvsequist@partners.org FU Genentech; Dana-Farber/Harvard Cancer Center SPORE in Lung Cancer, National Cancer Institute [P50 CA090578]; LUNGevity Foundation & Goldman Philanthropic Partnerships FX This work was supported by Genentech and the Dana-Farber/Harvard Cancer Center SPORE in Lung Cancer, National Cancer Institute P50 CA090578 (JES).; Joel Neal received research funding from Genentech. Panos Fidias is on the advisory board for Genentech. Alice Shaw has consulted for Pfizer, Ariad, Chugai, Novartis, Millenium, and Daiichi. Thomas Lynch is a consultant for Merck, Supergen, and Boehringer-Ingelheim, is on the Board of Directors for Infinity, and is a joint holder for a patent for EGFR mutation testing. Sreenath Sharma received a grant from the LUNGevity Foundation & Goldman Philanthropic Partnerships, consulted for Concert Pharmaceuticals, and is employed by Norvartis. Jeffrey Settleman is employed by Genentech. Lecia Sequist received a grant from Genentech and is on the advisory boards for Clovis Oncology, Celgene, GSK, Daiichi Sankyo, and Merrimack. The remaining authors declare no conflict of interest. NR 28 TC 38 Z9 40 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD OCT PY 2012 VL 7 IS 10 BP 1602 EP 1608 DI 10.1097/JTO.0b013e318262de4a PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 007WP UT WOS:000308919400023 PM 22878749 ER PT J AU Freudiger, CW Pfannl, R Orringer, DA Saar, BG Ji, MB Zeng, Q Ottoboni, L Ying, W Waeber, C Sims, JR De Jager, PL Sagher, O Philbert, MA Xu, XY Kesari, S Xie, XS Young, GS AF Freudiger, Christian W. Pfannl, Rolf Orringer, Daniel A. Saar, Brian G. Ji, Minbiao Zeng, Qing Ottoboni, Linda Ying, Wei Waeber, Christian Sims, John R. De Jager, Philip L. Sagher, Oren Philbert, Martin A. Xu, Xiaoyin Kesari, Santosh Xie, X. Sunney Young, Geoffrey S. TI Multicolored stain-free histopathology with coherent Raman imaging SO LABORATORY INVESTIGATION LA English DT Article DE CARS; Coherent anti-stokes Raman scattering; histology; in vivo microscopy; SRS; stimulated Raman scattering ID SCATTERING MICROSCOPY; IN-VIVO; 2ND-HARMONIC GENERATION; HIGH-SENSITIVITY; CARS MICROSCOPE; TISSUES; BRAIN; RESOLUTION; MYELIN; FLUORESCENCE AB Conventional histopathology with hematoxylin & eosin (H&E) has been the gold standard for histopathological diagnosis of a wide range of diseases. However, it is not performed in vivo and requires thin tissue sections obtained after tissue biopsy, which carries risk, particularly in the central nervous system. Here we describe the development of an alternative, multicolored way to visualize tissue in real-time through the use of coherent Raman imaging (CRI), without the use of dyes. CRI relies on intrinsic chemical contrast based on vibrational properties of molecules and intrinsic optical sectioning by nonlinear excitation. We demonstrate that multicolor images originating from CH2 and CH3 vibrations of lipids and protein, as well as two-photon absorption of hemoglobin, can be obtained with subcellular resolution from fresh tissue. These stain-free histopathological images show resolutions similar to those obtained by conventional techniques, but do not require tissue fixation, sectioning or staining of the tissue analyzed. Laboratory Investigation (2012) 92, 1492-1502; doi:10.1038/labinvest.2012.109; published online 20 August 2012 C1 [Zeng, Qing; Xu, Xiaoyin; Young, Geoffrey S.] Harvard Univ, Dept Radiol, Sch Med, Boston, MA 02115 USA. [Freudiger, Christian W.; Saar, Brian G.; Ji, Minbiao; Xie, X. Sunney] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Pfannl, Rolf] Tufts Med Ctr, Dept Pathol & Lab Med, Boston, MA USA. [Orringer, Daniel A.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Orringer, Daniel A.] Harvard Univ, Dept Neurosurg, Sch Med, Boston, MA 02115 USA. [Orringer, Daniel A.; Sagher, Oren] Univ Michigan, Sch Med, Dept Neurosurg, Ann Arbor, MI USA. [Ottoboni, Linda; De Jager, Philip L.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Ying, Wei; Waeber, Christian; Sims, John R.] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. [De Jager, Philip L.] Harvard Univ, Dept Neurol, Sch Med, Boston, MA 02115 USA. [De Jager, Philip L.] Broad Inst Harvard Univ & MIT, Boston, MA USA. [Philbert, Martin A.] Univ Michigan, Dept Environm & Hlth Sci, Ann Arbor, MI 48109 USA. [Kesari, Santosh] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kesari, Santosh] Univ Calif San Diego, Dept Neurosci, Moores Canc Ctr, San Diego, CA 92103 USA. [Young, Geoffrey S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Young, GS (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. EM xie@chemistry.harvard.edu; gsyoung@partners.org RI Kesari, Santosh/E-8461-2013; Waeber, Christian/A-8333-2009; Ji, Minbiao/C-7793-2011; OI Waeber, Christian/0000-0001-6078-0027; Ji, Minbiao/0000-0002-9066-4008; OTTOBONI, LINDA/0000-0001-5412-7785 FU Boehringer Ingelheim Fonds; Army Research Office; Italian Society of Multiple Sclerosis (FISM) [Cod 2008/B/5]; NIH [R01NS049263]; NSF [0958345]; NIH/NIBIB [1R01EB010244-01] FX We thank Dr John Sims for the mouse stroke model, Chrissy Rooney for the invasive glioma model, Dr Fa-Ke Lu and Srinjan Basu for the cell images, and Dr Anita Huettner for early pathology work. Funding: CWF and BUS thank Boehringer Ingelheim Fonds for a Ph.D. Fellowship and the Army Research Office for a National Defense Science and Engineering Graduate Fellowship, respectively. LO acknowledges the Italian Society of Multiple Sclerosis (FISM, Cod 2008/B/5). PLD is a Harry Weaver neuroscience scholar of the National Multiple Sclerosis society and CW acknowledges NIH (R01NS049263). The work of X Xu was supported by the NSF award 0958345. This work was supported by the NIH Directors Pioneer Award (to XSX) and NIH/NIBIB T-R01 (grant 1R01EB010244-01). NR 42 TC 41 Z9 41 U1 3 U2 41 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD OCT PY 2012 VL 92 IS 10 BP 1492 EP 1502 DI 10.1038/labinvest.2012.109 PG 11 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 013RX UT WOS:000309324600011 PM 22906986 ER PT J AU Yeung, CK Chan, NPY Shek, SYN Chan, HHL AF Yeung, Chi K. Chan, Nicola P. Y. Shek, Samantha Y. N. Chan, Henry H. L. TI Evaluation of combined fractional radiofrequency and fractional laser treatment for acne scars in Asians SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE acne scar; fractional radiofrequency; laser; Asian; post-inflammatory hyperpigmentation ID SKIN REJUVENATION; DIODE-LASER; YAG LASER; PHOTOTHERMOLYSIS; COMPLICATIONS; IMPROVEMENT; TECHNOLOGY; EXPERIENCE; SYSTEM; IV AB Background and Objectives Fractionated radiofrequency (RF) induces deep dermal heating and leaves the epidermis less affected. We studied the efficacy and safety of bipolar RF and fractional diode laser followed by fractional RF in Asians with acne scars. Materials and Methods Twenty-four patients (skin types III and IV) with acne scars received up to five treatments of combined fractional 915-nm laser and bipolar RF using a Matrix IR applicator (Syneron Medical Ltd, Yokneam, Israel) with fluence ranging from 50 to 70?J/cm2, RF at 70100?J/cm3, double passes followed by full-face bipolar fractional RF treatment using Matrix RF at energy ranging from 50 to 62?mJ/pin, at 4-week intervals. Changes in acne scars, skin texture, pore size, pigmentation irregularity, and complications were assessed up to 3 months post-treatment by standardized photographs obtained with Canfield Visia-CR system (R). Subjective improvement and patient satisfaction were assessed by questionnaire. Results Twenty patients (age 27.7?+/-?8.4 years) completed the study. Modest but statistically significant improvement was noted in acne scars, with the mean grade decreased by 29% (P? 20 providers per practice (the lower bound for current CMP practice surveys). Results: Among primary care physicians (n = 350,350), only 2.1% of practices consisted of > 20 providers. Among behavioral health practitioners (n = 146,992) and psychiatrists (n = 44,449), 1.3% and 1.0% of practices, respectively, had > 20 providers. Sensitivity analysis excluding single-physician practices as "secondary" confirmed findings, with primary care and psychiatrist practices of > 20 providers comprising, respectively, only 19.4% and 8.8% of practices (difference: P < 0.0001). In secondary analyses, bipolar disorder was used as a tracer condition to estimate practice census for a high-complexity, high-cost behavioral health condition; only 1.3-18 patients per practice had claims for this condition. Conclusions: The tax identification number method for estimating practice size has strengths and limitations that complement those of survey methods. The proportion of practices below the lower bound of prior CMP studies is substantial, and care models and policies will need to address the needs of such practices and their patients. Achieving a critical mass of patients for disorder-specific CMPs will require coordination across multiple small practices. C1 [Bauer, Mark S.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02130 USA. [Bauer, Mark S.] VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. [Leader, Deane; Un, Hyong] Aetna Inc, Aetna Behav Hlth, Blue Bell, PA USA. [Lai, Zongshan; Kilbourne, Amy M.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Lai, Zongshan; Kilbourne, Amy M.] VA Ann Arbor HSR&D Ctr Excellence, Ann Arbor, MI USA. RP Bauer, MS (reprint author), Harvard Univ, Sch Med, Dept Psychiat, VA Boston Healthcare Syst 152 M,150 S Huntingting, Boston, MA 02130 USA. EM mark.bauer@va.gov FU NIMH [R-01-MH079994]; VA Health Services Research and Development Center of Excellence; Center for Organization, Leadership, & Management Research (COLMR) FX Supported in part by NIMH Grant R-01-MH079994 (AMK) as well as the VA Health Services Research and Development Center of Excellence, The Center for Organization, Leadership, & Management Research (COLMR) (MSB). NR 48 TC 7 Z9 7 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD OCT PY 2012 VL 50 IS 10 BP 843 EP 848 DI 10.1097/MLR.0b013e31825f2864 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 009XM UT WOS:000309058700004 PM 22814854 ER PT J AU Koo, S Sutton, DA Yeh, WW Thompson, EH Sigler, L Shearer, JF Hofstra, DE Wickes, BL Marty, FM AF Koo, Sophia Sutton, Deanna A. Yeh, Wendy W. Thompson, Elizabeth H. Sigler, Lynne Shearer, Judy F. Hofstra, Deborah E. Wickes, Brian L. Marty, Francisco M. TI Invasive Mycoleptodiscus fungal cellulitis and myositis SO MEDICAL MYCOLOGY LA English DT Article DE Mycoleptodiscus; invasive fungal disease; dematiaceous; temozolomide ID PATIENTS RECEIVING TEMOZOLOMIDE; GLIOBLASTOMA-MULTIFORME; DOSE TEMOZOLOMIDE; INDICUS INFECTION; PHEOHYPHOMYCOSIS; LYMPHOPENIA; MELANOMA; THERAPY AB We report progressive necrotizing fungal cellulitis and myositis in the leg of a patient with glioblastoma multiforme treated with temozolomide and corticosteroids. While the morphologic appearance of the isolate and its ability to grow at temperatures greater than 32 degrees C were suggestive of Mycoleptodiscus indicus, some of the conidia were atypical for this species in that they had single septa and occasional lateral appendages. Furthermore, the isolate was different from M. indicus based on the sequencing analysis of two rDNA regions. This is the first case of Mycoleptodiscus invasive fungal disease in which the causative agent could not be resolved at the species level because of inconsistencies between morphological and molecular data. C1 [Koo, Sophia; Yeh, Wendy W.; Marty, Francisco M.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Koo, Sophia; Yeh, Wendy W.; Marty, Francisco M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Koo, Sophia; Yeh, Wendy W.; Marty, Francisco M.] Harvard Univ, Sch Med, Boston, MA USA. [Sutton, Deanna A.; Thompson, Elizabeth H.; Wickes, Brian L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, Fungus Testing Lab, San Antonio, TX 78229 USA. [Sigler, Lynne] Univ Alberta Microfungus Collect & Herbarium, Devonian Bot Garden, Edmonton, AB, Canada. [Shearer, Judy F.] USA, Corps Engineers, Engn Res & Dev Ctr, Vicksburg, MS 39180 USA. [Hofstra, Deborah E.] Natl Inst Water & Atmospher Res, Hamilton, New Zealand. RP Koo, S (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St,PBB-A4, Boston, MA 02115 USA. EM skoo@partners.org OI Koo, Sophia/0000-0002-4973-7439 NR 26 TC 1 Z9 1 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD OCT PY 2012 VL 50 IS 7 BP 740 EP 745 DI 10.3109/13693786.2012.656717 PG 6 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 008HV UT WOS:000308948900008 PM 22332907 ER PT J AU Healy, BC Schoenfeld, D AF Healy, Brian C. Schoenfeld, David TI COMPARISON OF ANALYSIS APPROACHES FOR PHASE III CLINICAL TRIALS IN AMYOTROPHIC LATERAL SCLEROSIS SO MUSCLE & NERVE LA English DT Article DE amyotrophic lateral sclerosis; clinical trial; longitudinal analysis; sample size calculations; survival analysis ID PLACEBO-CONTROLLED TRIAL; FUNCTIONAL RATING-SCALE; LONGITUDINAL DATA; ALS; MODELS; MULTICENTER AB Introduction: In this study we explore several methods for incorporating survival information in the analysis of Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) scores. Methods: ALSFRS scores and patient survival times were simulated based on estimates from a recent clinical trial. Six analysis approaches were applied to the data. Each approach was based on ALSFRS scores, the survival time, or a combination of the 2. The power of each approach to detect potential treatment effects was estimated. Results: When the treatment acted solely on the change in ALSFRS, the shared parameter model provided the most power, although all of the models based on random effects were similar. As the effect on survival increased, rank-based analysis showed potential gains in power. Survival analysis was superior under a small effect on ALSFRS and a larger effect on mortality. Conclusions: The shared parameter model and rank-based approach can offer improvements in power over traditional approaches. Muscle Nerve 46: 506-511, 2012 C1 [Healy, Brian C.; Schoenfeld, David] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Healy, Brian C.] Brigham & Womens Hosp, Partners MS Ctr, Brookline, MA USA. [Schoenfeld, David] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Healy, BC (reprint author), Massachusetts Gen Hosp, Ctr Biostat, 50 Staniford St,Suite 560, Boston, MA 02114 USA. EM bchealy@partners.org NR 17 TC 11 Z9 11 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0148-639X EI 1097-4598 J9 MUSCLE NERVE JI Muscle Nerve PD OCT PY 2012 VL 46 IS 4 BP 506 EP 511 DI 10.1002/mus.23392 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 007FR UT WOS:000308874700005 PM 22987690 ER PT J AU Kim, KS Kim, S Beack, S Yang, JA Yun, SH Hahn, SK AF Kim, Ki Su Kim, Seonghoon Beack, Songeun Yang, Jeong-A Yun, Seok Hyun Hahn, Sei Kwang TI In vivo real-time confocal microscopy for target-specific delivery of hyaluronic acid-quantum dot conjugates SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Article DE Hyaluronic acid; Quantum dots; Confocal microscopy; Bioimaging; Drug delivery ID ENDOCYTOSIS; RECEPTOR; COMPLEX AB Hyaluronic acid (HA), which is a biocompatible, biodegradable, and linear polysaccharide in the body, has been widely used for various biomedical applications. In this work, real-time bioimaging for target-specific delivery of HA derivatives was carried out using quantum dots (QDs). In vitro confocal microscopy of HA-QD conjugates confirmed the intracellular delivery of HA derivatives to B16F1 cells with HA receptors by HA-receptor-mediated endocytosis. Furthermore in vivo real-time confocal microscopy of HA-QD conjugates successfully visualized the target specific delivery and accumulation of HA-QD conjugates from the fluorescence-labeled blood vessels to the liver tissues. The authors could confirm the feasibility of HA derivatives as a target-specific intracellular drug-delivery carrier for the treatment of liver diseases and the in vivo real-time confocal microscopy as a new bioimaging tool for various drug-delivery applications. From the Clinical Editor: This study demonstrates the possibility of labeling hyaluronic acid with quantum dots for visualization and for targeted intracellular drug delivery in liver disease models. (C) 2012 Elsevier Inc. All rights reserved. C1 [Kim, Ki Su; Beack, Songeun; Yang, Jeong-A; Hahn, Sei Kwang] Pohang Univ Sci & Technol Pohang, Dept Mat Sci & Engn, Pohang, South Korea. [Kim, Seonghoon; Yun, Seok Hyun] Korea Adv Inst Sci & Technol, Grad Sch Nanosci & Technol, Taejon, South Korea. [Yun, Seok Hyun; Hahn, Sei Kwang] Harvard Univ, Sch Med, Wellman Ctr Photomed, Cambridge, MA 02138 USA. [Yun, Seok Hyun; Hahn, Sei Kwang] Massachusetts Gen Hosp, Cambridge, MA USA. RP Hahn, SK (reprint author), Pohang Univ Sci & Technol Pohang, Dept Mat Sci & Engn, Pohang, South Korea. EM skhanb@postech.ac.kr FU Convergence Research Center Program; Mid-career Researcher Program; National Research Foundation (NRF) of Korea; Ministry of Education, Science and Technology [2009-0081871, 2009-0084578, R31-2008-000-10071-0] FX This research was supported by the Convergence Research Center Program, Mid-career Researcher Program and the WCU Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Education, Science and Technology (2009-0081871, 2009-0084578 and R31-2008-000-10071-0). NR 10 TC 11 Z9 11 U1 7 U2 44 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD OCT PY 2012 VL 8 IS 7 BP 1070 EP 1073 DI 10.1016/j.nano.2012.05.014 PG 4 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 012DS UT WOS:000309216300003 PM 22687895 ER PT J AU Anastasiou, D Yu, YM Israelsen, WJ Jiang, JK Boxer, MB Hong, BS Tempel, W Dimov, S Shen, M Jha, A Yang, H Mattaini, KR Metallo, CM Fiske, BP Courtney, KD Malstrom, S Khan, TM Kung, C Skoumbourdis, AP Veith, H Southall, N Walsh, MJ Brimacombe, KR Leister, W Lunt, SY Johnson, ZR Yen, KE Kunii, K Davidson, SM Christofk, HR Austin, CP Inglese, J Harris, MH Asara, JM Stephanopoulos, G Salituro, FG Jin, SF Dang, L Auld, DS Park, HW Cantley, LC Thomas, CJ Heiden, MGV AF Anastasiou, Dimitrios Yu, Yimin Israelsen, William J. Jiang, Jian-Kang Boxer, Matthew B. Hong, Bum Soo Tempel, Wolfram Dimov, Svetoslav Shen, Min Jha, Abhishek Yang, Hua Mattaini, Katherine R. Metallo, Christian M. Fiske, Brian P. Courtney, Kevin D. Malstrom, Scott Khan, Tahsin M. Kung, Charles Skoumbourdis, Amanda P. Veith, Henrike Southall, Noel Walsh, Martin J. Brimacombe, Kyle R. Leister, William Lunt, Sophia Y. Johnson, Zachary R. Yen, Katharine E. Kunii, Kaiko Davidson, Shawn M. Christofk, Heather R. Austin, Christopher P. Inglese, James Harris, Marian H. Asara, John M. Stephanopoulos, Gregory Salituro, Francesco G. Jin, Shengfang Dang, Lenny Auld, Douglas S. Park, Hee-Won Cantley, Lewis C. Thomas, Craig J. Heiden, Matthew G. Vander TI Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis SO NATURE CHEMICAL BIOLOGY LA English DT Article ID CANCER-CELL METABOLISM; TUMOR-GROWTH; NUCLEAR TRANSLOCATION; THYROID-HORMONE; BINDING PROTEIN; ISOFORM; FRUCTOSE-1,6-BISPHOSPHATE; ISOZYME; INHIBITION; CONVERSION AB Cancer cells engage in a metabolic program to enhance biosynthesis and support cell proliferation. The regulatory properties of pyruvate kinase M2 (PKM2) influence altered glucose metabolism in cancer. The interaction of PKM2 with phosphotyrosine-containing proteins inhibits enzyme activity and increases the availability of glycolytic metabolites to support cell proliferation. This suggests that high pyruvate kinase activity may suppress tumor growth. We show that expression of PKM1, the pyruvate kinase isoform with high constitutive activity, or exposure to published small-molecule PKM2 activators inhibits the growth of xenograft tumors. Structural studies reveal that small-molecule activators bind PKM2 at the subunit interaction interface, a site that is distinct from that of the endogenous activator fructose-1,6-bisphosphate (FBP). However, unlike FBP, binding of activators to PKM2 promotes a constitutively active enzyme state that is resistant to inhibition by tyrosine-phosphorylated proteins. These data support the notion that small-molecule activation of PKM2 can interfere with anabolic metabolism. C1 [Anastasiou, Dimitrios; Courtney, Kevin D.; Christofk, Heather R.; Asara, John M.; Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Dept Med, Div Signal Transduct, Boston, MA 02215 USA. [Anastasiou, Dimitrios; Courtney, Kevin D.; Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Yu, Yimin; Israelsen, William J.; Mattaini, Katherine R.; Fiske, Brian P.; Malstrom, Scott; Khan, Tahsin M.; Lunt, Sophia Y.; Johnson, Zachary R.; Davidson, Shawn M.; Heiden, Matthew G. Vander] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Jiang, Jian-Kang; Boxer, Matthew B.; Shen, Min; Skoumbourdis, Amanda P.; Veith, Henrike; Southall, Noel; Walsh, Martin J.; Brimacombe, Kyle R.; Leister, William; Austin, Christopher P.; Inglese, James; Auld, Douglas S.; Thomas, Craig J.] Natl Ctr Adv Translat Sci, NIH, Chem Genom Ctr, Bethesda, MD USA. [Hong, Bum Soo; Tempel, Wolfram; Dimov, Svetoslav; Park, Hee-Won] Univ Toronto, Struct Genom Consortium, Toronto, ON, Canada. [Jha, Abhishek; Stephanopoulos, Gregory] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Yang, Hua; Kung, Charles; Yen, Katharine E.; Kunii, Kaiko; Salituro, Francesco G.; Jin, Shengfang; Dang, Lenny] Agios Pharmaceut, Cambridge, MA USA. [Metallo, Christian M.] Univ Calif San Diego, Dept Bioengn, San Diego, CA 92103 USA. [Courtney, Kevin D.; Heiden, Matthew G. Vander] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Harris, Marian H.] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. [Asara, John M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Park, Hee-Won] Univ Toronto, Dept Pharmacol, Toronto, ON, Canada. RP Anastasiou, D (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Signal Transduct, Boston, MA 02215 USA. EM mvh@mit.edu RI Cantley, Lewis/D-1800-2014; Southall, Noel/H-8991-2012; OI Cantley, Lewis/0000-0002-1298-7653; Southall, Noel/0000-0003-4500-880X; Lunt, Sophia/0000-0003-4522-6065 FU Canadian Institutes of Health Research; Howard Hughes Medical Institute; Intramural NIH HHS; NCI NIH HHS [5P01CA120964, 5P30CA006516, 5P30CA1405141, P01 CA120964, P30 CA006516]; NIGMS NIH HHS [R01 GM056203, R01 GM56203, T32 GM007287]; NIMH NIH HHS [R03 MH085679, R03MH085679]; Wellcome Trust NR 43 TC 177 Z9 180 U1 5 U2 59 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 EI 1552-4469 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD OCT PY 2012 VL 8 IS 10 BP 839 EP 847 DI 10.1038/NCHEMBIO.1060 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 009WN UT WOS:000309056200009 PM 22922757 ER PT J AU Lin, CX Jungmann, R Leifer, AM Li, C Levner, D Church, GM Shih, WM Yin, P AF Lin, Chenxiang Jungmann, Ralf Leifer, Andrew M. Li, Chao Levner, Daniel Church, George M. Shih, William M. Yin, Peng TI Submicrometre geometrically encoded fluorescent barcodes self-assembled from DNA SO NATURE CHEMISTRY LA English DT Article ID SUPERRESOLUTION MICROSCOPY; NANOSCALE SHAPES; GENE-EXPRESSION; FUSION PROTEINS; FOLDING DNA; ORIGAMI; MOLECULES; CELLS; SYSTEM; GUIDE AB The identification and differentiation of a large number of distinct molecular species with high temporal and spatial resolution is a major challenge in biomedical science. Fluorescence microscopy is a powerful tool, but its multiplexing ability is limited by the number of spectrally distinguishable fluorophores. Here, we used (deoxy) ribonucleic acid (DNA)-origami technology to construct submicrometre nanorods that act as fluorescent barcodes. We demonstrate that spatial control over the positioning of fluorophores on the surface of a stiff DNA nanorod can produce 216 distinct barcodes that can be decoded unambiguously using epifluorescence or total internal reflection fluorescence microscopy. Barcodes with higher spatial information density were demonstrated via the construction of super-resolution barcodes with features spaced by similar to 40 nm. One species of the barcodes was used to tag yeast surface receptors, which suggests their potential applications as in situ imaging probes for diverse biomolecular and cellular entities in their native environments. C1 [Lin, Chenxiang; Jungmann, Ralf; Li, Chao; Levner, Daniel; Church, George M.; Shih, William M.; Yin, Peng] Harvard Univ, Wyss Inst Biologically Inspired Engn, Boston, MA 02115 USA. [Lin, Chenxiang; Shih, William M.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Lin, Chenxiang; Shih, William M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Jungmann, Ralf; Yin, Peng] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Leifer, Andrew M.] Harvard Univ, Program Biophys, Cambridge, MA 02138 USA. [Li, Chao; Levner, Daniel; Church, George M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Lin, CX (reprint author), Harvard Univ, Wyss Inst Biologically Inspired Engn, Boston, MA 02115 USA. EM william_shih@dfci.harvard.edu; py@hms.harvard.edu RI Lin, Chenxiang/G-2303-2010; Jungmann, Ralf/A-6357-2015 OI Jungmann, Ralf/0000-0003-4607-3312 FU National Institutes of Health (NIH) [1DP2OD007292, 1DP2OD004641]; National Science Foundation [CCF1054898]; Office of Naval Research [N000141110914, N000141010827]; Wyss Institute for Biologically Engineering Faculty; Wyss Institute for Biologically Inspired Engineering Faculty; National Human Genome Research Institute, Centers of Excellence in Genomic Science; Alexander von Humboldt-Foundation FX We thank C. Steinhauer and S. P. Laurien for help with super-resolution microscopy software development, the Harvard Center for Biological Imaging, as well as the Nikon Imaging Center at Harvard Medical School, for the use of their microscopes and S. M. Douglas for providing the transmission electron microscopy images used in Supplementary Fig. S5. This work is supported by a National Institutes of Health (NIH) Director's New Innovator Award (1DP2OD007292), a National Science Foundation Faculty Early Career Development Award (CCF1054898), an Office of Naval Research Young Investigator Program Award (N000141110914), an Office of Naval Research grant (N000141010827) and a Wyss Institute for Biologically Engineering Faculty Startup Fund to P.Y., and an NIH Director's New Innovator Award (1DP2OD004641) and a Wyss Institute for Biologically Inspired Engineering Faculty Award to W. M. S. C. Li, D. L. and G. M. C. acknowledge support from the National Human Genome Research Institute, Centers of Excellence in Genomic Science. R.J. acknowledges support from the Alexander von Humboldt-Foundation through a Feodor Lynen fellowship. NR 50 TC 77 Z9 78 U1 7 U2 130 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1755-4330 J9 NAT CHEM JI Nat. Chem. PD OCT PY 2012 VL 4 IS 10 BP 832 EP 839 DI 10.1038/NCHEM.1451 PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 011HC UT WOS:000309154700016 PM 23000997 ER PT J AU Fu, WX Ergun, A Lu, T Hill, JA Haxhinasto, S Fassett, MS Gazit, R Adoro, S Glimcher, L Chan, S Kastner, P Rossi, D Collins, JJ Mathis, D Benoist, C AF Fu, Wenxian Ergun, Ayla Lu, Ting Hill, Jonathan A. Haxhinasto, Sokol Fassett, Marlys S. Gazit, Roi Adoro, Stanley Glimcher, Laurie Chan, Susan Kastner, Philippe Rossi, Derrick Collins, James J. Mathis, Diane Benoist, Christophe TI A multiply redundant genetic switch 'locks in' the transcriptional signature of regulatory T cells SO NATURE IMMUNOLOGY LA English DT Article ID LINEAGE IN-VIVO; FACTOR FOXP3; SUPPRESSIVE FUNCTION; DIFFERENTIATION; EXPRESSION; T(H)17; SPECIFICATION; POPULATION; GENERATION; RESPONSES AB The transcription factor Foxp3 participates dominantly in the specification and function of Foxp3(+)CD4(+) regulatory T cells (T-reg cells) but is neither strictly necessary nor sufficient to determine the characteristic T-reg cell signature. Here we used computational network inference and experimental testing to assess the contribution of other transcription factors to this. Enforced expression of Helios or Xbp1 elicited distinct signatures, but Eos, IRF4, Satb1, Lef1 and GATA-1 elicited exactly the same outcome, acting in synergy with Foxp3 to activate expression of most of the T-reg cell signature, including key transcription factors, and enhancing occupancy by Foxp3 at its genomic targets. Conversely, the T-reg cell signature was robust after inactivation of any single cofactor. A redundant genetic switch thus 'locked in' the T-reg cell phenotype, a model that would account for several aspects of T-reg cell physiology, differentiation and stability. C1 [Ergun, Ayla; Lu, Ting; Collins, James J.] Boston Univ, Howard Hughes Med Inst, Dept Biomed Engn, Boston, MA 02215 USA. [Fu, Wenxian; Ergun, Ayla; Hill, Jonathan A.; Haxhinasto, Sokol; Fassett, Marlys S.; Mathis, Diane; Benoist, Christophe] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA 02115 USA. [Ergun, Ayla; Lu, Ting; Collins, James J.] Boston Univ, Ctr BioDynam, Boston, MA 02215 USA. [Lu, Ting] Univ Illinois, Dept Bioengn, Urbana, IL USA. [Gazit, Roi; Rossi, Derrick] Childrens Hosp, Immune Dis Inst, Program Cellular & Mol Med, Boston, MA 02115 USA. [Adoro, Stanley; Glimcher, Laurie] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. [Chan, Susan; Kastner, Philippe] Inst Genet & Biol Mol & Cellulaire, Illkirch Graffenstaden, France. RP Mathis, D (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Div Immunol, Boston, MA 02115 USA. EM cbdm@hms.harvard.edu; cbdm@hms.harvard.edu OI Gazit, Roi/0000-0002-0548-2147 FU US National Institutes of Health [AI051530, AI072073, T32 DK7260, 3R24AI072073-03S1]; GlaxoSmithKline; Damon Runyon Cancer Research Foundation; American Diabetes Association [7-07-BETA-14]; Canadian Institutes of Health Research FX We thank R. Samstein and A. Rudensky for the unpublished ChIP-seq data; S. Smale (University of California, Los Angeles) for mouse cDNA encoding Helios; M. Calderwood and the Center for Cancer Systems Biology for expression cDNA; P. Rahl for advice on ChIP-Seq; J. Ericson, S. Davis, H. Paik and R. Cruse for genomic data analysis; H. Chen and Q. Cai for experimental support; and J. LaVecchio and G. Buruzala for sorting. This work benefited from public data generated by the Immunological Genome Project consortium. Supported by the US National Institutes of Health (AI051530 to C.B. and D.M.; AI072073 to C.B., D.M. and J.C.; training grant T32 DK7260 for support of M.S.F.; and 3R24AI072073-03S1 for support of A.E.), GlaxoSmithKline, the Damon Runyon Cancer Research Foundation (S.H.), the American Diabetes Association (7-07-BETA-14 to W.F.) and the Canadian Institutes of Health Research (J.H.). NR 47 TC 98 Z9 100 U1 3 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD OCT PY 2012 VL 13 IS 10 BP 972 EP 980 DI 10.1038/ni.2420 PG 9 WC Immunology SC Immunology GA 009PV UT WOS:000309038600013 PM 22961053 ER PT J AU Cavender, MA Ellis, SG AF Cavender, Matthew A. Ellis, Stephen G. TI INTERVENTIONAL CARDIOLOGY Stent choice and the hidden consequences of cost savings SO NATURE REVIEWS CARDIOLOGY LA English DT Editorial Material ID BARE METAL STENTS; PERCUTANEOUS CORONARY INTERVENTION; DRUG-ELUTING STENTS; SIRIUS TRIAL; RESTENOSIS; SAFETY; RISK AB Amin and colleagues have attempted to estimate the cost savings to the US health-care system if drug-eluting coronary stents were more selectively used in patients at low risk of restenosis. Their results and conclusions raise statistical, societal, and ethical issues that need to be considered before this approach should be widely embraced. C1 [Ellis, Stephen G.] Cleveland Clin, Inst Heart & Vasc, Cleveland, OH 44195 USA. [Cavender, Matthew A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp,Div Cardiovasc Med,Dept Med, Boston, MA 02115 USA. RP Ellis, SG (reprint author), Cleveland Clin, Inst Heart & Vasc, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM elliss@ccf.org NR 10 TC 1 Z9 1 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1759-5002 J9 NAT REV CARDIOL JI Nat. Rev. Cardiol. PD OCT PY 2012 VL 9 IS 10 BP 559 EP 560 DI 10.1038/nrcardio.2012.124 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 012CB UT WOS:000309211900003 PM 22922596 ER PT J AU Ben-Ari, Y Khalilov, I Kahle, KT Cherubini, E AF Ben-Ari, Yehezkel Khalilov, Ilgam Kahle, Kristopher T. Cherubini, Enrico TI The GABA Excitatory/Inhibitory Shift in Brain Maturation and Neurological Disorders SO NEUROSCIENTIST LA English DT Article DE GABA; excitation/inhibition; neonatal neurons; epilepsies; bumetanide; NKCC1; KCC2; phenobarbital; diazepam; GABA-acting antiepileptic drugs ID NEONATAL-RAT HIPPOCAMPUS; GIANT DEPOLARIZING POTENTIALS; TEMPORAL-LOBE EPILEPSY; LONG-TERM POTENTIATION; K-CL COTRANSPORTER; NEURONAL CHLORIDE ACCUMULATION; IN-VITRO; DEVELOPING NEOCORTEX; NETWORK ACTIVITY; EXCITATORY ACTIONS AB Ionic currents and the network-driven patterns they generate differ in immature and adult neurons: The developing brain is not a "small adult brain." One of the most investigated examples is the developmentally regulated shift of actions of the transmitter GABA that inhibit adult neurons but excite immature ones because of an initially higher intracellular chloride concentration [Cl-](i), leading to depolarizing and often excitatory actions of GABA instead of hyperpolarizing and inhibitory actions. The levels of [Cl-](i) are also highly labile, being readily altered transiently or persistently by enhanced episodes of activity in relation to synaptic plasticity or a variety of pathological conditions, including seizures and brain insults. Among the plethora of channels, transporters, and other devices involved in controlling [Cl-](i), two have emerged as playing a particularly important role: the chloride importer NKCC1 and the chloride exporter KCC2. Here, the authors stress the importance of determining how [Cl-](i) is dynamically regulated and how this affects brain operation in health and disease. In a clinical perspective, agents that control [Cl-](i) and reinstate inhibitory actions of GABA open novel therapeutic perspectives in many neurological disorders, including infantile epilepsies, autism spectrum disorders, and other developmental disorders. C1 [Ben-Ari, Yehezkel; Khalilov, Ilgam] INSERM, INMED, U901, F-13258 Marseille, France. [Ben-Ari, Yehezkel; Khalilov, Ilgam] Neurochlore, Marseille, France. [Kahle, Kristopher T.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Kahle, Kristopher T.] Harvard Univ, Sch Med, Boston, MA USA. [Cherubini, Enrico] Int Sch Adv Studies SISSA, Trieste, Italy. RP Ben-Ari, Y (reprint author), INMED & CEO Neurochlore, INMED Campus Sci Luminy,163 Route Luminy, F-13273 Marseilles 09, France. EM ben-ari@inmed.univ-mrs.fr RI Khalilov, Ilgam/B-5267-2015 OI Khalilov, Ilgam/0000-0002-9468-4778 FU French Medical Research council (INSERM); French Medical Research (FRM) association; French Federation of Brain Research (FRC); European Union grants (EU No); Ministero Universita e Ricerca (MIUR, Italy); telethon grant [GGP11043] FX The authors disclosed receipt of the following financial support for the research and/or authorship of this article: This work was supported by the French Medical Research council (INSERM), the French Medical Research (FRM) association, the French Federation of Brain Research (FRC), European Union grants (EU No), Ministero Universita e Ricerca (MIUR, Italy), and telethon grant GGP11043. NR 142 TC 127 Z9 129 U1 10 U2 46 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-8584 EI 1089-4098 J9 NEUROSCIENTIST JI Neuroscientist PD OCT PY 2012 VL 18 IS 5 BP 467 EP 486 DI 10.1177/1073858412438697 PG 20 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 011IC UT WOS:000309157300005 PM 22547529 ER PT J AU Meehan, WP Zhang, J Mannix, R Whalen, MJ AF Meehan, William P., III Zhang, Jimmy Mannix, Rebekah Whalen, Michael J. TI Increasing Recovery Time Between Injuries Improves Cognitive Outcome After Repetitive Mild Concussive Brain Injuries in Mice SO NEUROSURGERY LA English DT Article DE Cell death; Concussion; Mice; Mild traumatic brain injury; Morris water maze; Repeated traumatic brain injury; Sport-related concussion ID FLUID-PERCUSSION INJURY; CEREBRAL CONCUSSION; UNITED-STATES; HEAD-INJURIES; BLOOD-FLOW; SPORTS; PERFORMANCE; FOOTBALL; IMPACT; RATS AB BACKGROUND: Although previous evidence suggests that the cognitive effects of concussions are cumulative, the effect of time interval between repeat concussions is largely unknown. OBJECTIVE: To determine the effect of time interval between repeat concussions on the cognitive function of mice. METHODS: We used a weight-drop model of concussion to subject anesthetized mice to 1, 3, 5, or 10 concussions, each a day apart. Additional mice were subjected to 5 concussions at varying time intervals: daily, weekly, and monthly. Morris water maze performance was measured 24 hours, 1 month, and 1 year after final injury. RESULTS: After 1 concussion, injured and sham-injured mice performed similarly in the Morris water maze. As the number of concussions increased, injured mice performed worse than sham-injured mice. Mice sustaining 5 concussions either 1 day or 1 week apart performed worse than sham-injured mice. When 5 concussions were delivered at 1-month time intervals, no difference in Morris water maze performance was observed between injured and sham-injured mice. After a 1-month recovery period, mice that sustained 5 concussions at daily and weekly time intervals continued to perform worse than sham-injured mice. One year after the final injury, mice sustaining 5 concussions at a daily time interval still performed worse than sham-injured mice. CONCLUSION: When delivered within a period of vulnerability, the cognitive effects of multiple concussions are cumulative, persistent, and may be permanent. Increasing the time interval between concussions attenuates the effects on cognition. When multiple concussions are sustained by mice daily, the effects on cognition are long term. C1 [Meehan, William P., III] Harvard Univ, Sch Med, Childrens Hosp Boston, Sports Concuss Clin,Div Sports Med,Dept Orthoped, Boston, MA 02115 USA. [Meehan, William P., III; Mannix, Rebekah] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Emergency Med,Dept Med, Boston, MA 02115 USA. [Meehan, William P., III; Mannix, Rebekah] Harvard Univ, Sch Med, Childrens Hosp Boston, Brain Injury Ctr, Boston, MA 02115 USA. [Meehan, William P., III; Zhang, Jimmy; Mannix, Rebekah; Whalen, Michael J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Neurosci, Boston, MA 02114 USA. [Whalen, Michael J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Meehan, William P., III] Micheli Ctr Sports Injury Prevent, Boston, MA USA. RP Meehan, WP (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Sports Concuss Clin,Div Sports Med,Dept Orthoped, 319 Longwood Ave, Boston, MA 02115 USA. EM concussion.sportsmed@childrens.harvard.edu; mwhalen@partners.org FU NICHD [T32 HD040128-06]; National Football League Charities; NINDS [5RO1NS047447, 1R21NS075226] FX This work was supported by grants from the NICHD T32 HD040128-06 (Dr Meehan), National Football League Charities (Drs Meehan, Mannix, and Whalen), and NINDS 5RO1NS047447 (Dr Whalen) and 1R21NS075226 (Dr Whalen). The authors have no personal financial or institutional interest in any of the drugs, materials, or devices described in this article. NR 45 TC 45 Z9 45 U1 2 U2 23 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD OCT PY 2012 VL 71 IS 4 BP 885 EP 891 DI 10.1227/NEU.0b013e318265a439 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 010TO UT WOS:000309117200045 PM 22743360 ER PT J AU Myers, AP Cantley, LC AF Myers, Andrea P. Cantley, Lewis C. TI Sugar free, cancer free? SO NUTRITION LA English DT Editorial Material ID INSULIN C1 [Myers, Andrea P.] Beth Israel Deaconess Med Ctr, Dana Farber Canc Inst, Dept Med Oncol, Div Signal Transduct, Boston, MA 02215 USA. [Cantley, Lewis C.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Signal Transduct,Dept Syst Biol, Boston, MA 02215 USA. RP Myers, AP (reprint author), Beth Israel Deaconess Med Ctr, Dana Farber Canc Inst, Dept Med Oncol, Div Signal Transduct, Boston, MA 02215 USA. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIGMS NIH HHS [R01 GM041890] NR 4 TC 4 Z9 4 U1 0 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-9007 J9 NUTRITION JI Nutrition PD OCT PY 2012 VL 28 IS 10 BP 1036 EP 1036 DI 10.1016/j.nut.2012.07.004 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 013QJ UT WOS:000309319600015 PM 22925542 ER PT J AU York-Best, CM Ecker, JL AF York-Best, Carey M. Ecker, Jeffrey L. TI Pelvic Examinations Under Anesthesia A Teachable Moment SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material C1 [York-Best, Carey M.; Ecker, Jeffrey L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Mem Obstet Serv, Boston, MA 02115 USA. RP York-Best, CM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Mem Obstet Serv, Boston, MA 02115 USA. EM cyorkbest@partners.org; jecker@partners.org NR 4 TC 1 Z9 1 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD OCT PY 2012 VL 120 IS 4 BP 741 EP 742 DI 10.1097/AOG.0b013e31826ce689 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 012FN UT WOS:000309221200001 PM 22996088 ER PT J AU Friedlander, AH Chang, TI Chantra, PK Aghazadehsanai, N Harada, ND Garrett, NR AF Friedlander, Arthur H. Chang, Tina I. Chantra, Prem K. Aghazadehsanai, Nona Harada, Nancy D. Garrett, Neal R. TI Do carotid atheromas on panoramic images prognosticate arterial calcifications on mammograms: acknowledged markers of future adverse cardiovascular events? SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY LA English DT Article ID CORONARY-HEART-DISEASE; SCREENING MAMMOGRAPHY; VASCULAR CALCIFICATIONS; INCREASED RISK; WOMEN; ASSOCIATION; RADIOGRAPHY; ATHEROSCLEROSIS; POPULATION; PREVALENCE AB Objective. The aim of this study was to evaluate the relationship between calcified carotid artery plaque (CCAP) on panoramic images and breast arterial calcifications (BAC) on mammograms, a validated independent risk indicator of fatal myocardial infarctions and strokes. Materials and Methods. Women >= 55 years old having CCAP diagnosed by their dentists had their mammograms evaluated for BAC by a physician. Other study variables were age, ethnicity, body mass index, and medications for hypertension, diabetes, and dyslipidemia. Descriptive and bivariate statistics and logistic regression were computed. Results. Researchers identified 40 women (mean age 62.2 +/- 6.2 years old) with CCAP, of whom 9 (prevalence rate 22.5%) also had BAC. The women with BAC tended to be older (65.1 vs 61.3 years old), more frequently hypertensive (100% vs 80.6%), and more frequently black than those without BAC, although these differences were not statistically significant (P > 0.10). Conclusions. CCAP on panoramic images of women is unrelated to the presence of BAC on mammograms. (Oral Surg Oral Med Oral Pathol Oral Radiol 2012;114:526-532) C1 [Friedlander, Arthur H.; Chang, Tina I.; Chantra, Prem K.; Aghazadehsanai, Nona] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Friedlander, Arthur H.; Chang, Tina I.; Garrett, Neal R.] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. [Chantra, Prem K.; Harada, Nancy D.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Friedlander, AH (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM arthur.friedlander@va.gov FU National Center for Research Resources, National Institutes of Health [CO6 Rr-14529-01]; Department of Veterans Affairs; University of California FX Elements of this investigation were conducted in a faciligy constructed with support from Research Facilities Improvement Program grant no. CO6 Rr-14529-01 from the National Center for Research Resources, National Institutes of Health.; None of the authors reports commercial associations with products and services described in this publication that might pose a potential, perceived, or real conflict of interest. All authors are full-time, salaried employees of either the Department of Veterans Affairs or the University of California. NR 36 TC 0 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2212-4403 J9 OR SURG OR MED OR PA JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. PD OCT PY 2012 VL 114 IS 4 BP 526 EP 532 DI 10.1016/j.oooo.2012.05.008 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 012AT UT WOS:000309208500028 PM 22986249 ER PT J AU Quesnel, AM Seton, M Merchant, SN Halpin, C McKenna, MJ AF Quesnel, Alicia M. Seton, Margaret Merchant, Saumil N. Halpin, Christopher McKenna, Michael J. TI Third-Generation Bisphosphonates for Treatment of Sensorineural Hearing Loss in Otosclerosis SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Bisphosphonates; Otosclerosis; Sensorineural hearing loss ID SODIUM-FLUORIDE TREATMENT; POSTMENOPAUSAL OSTEOPOROSIS; COCHLEAR OTOSCLEROSIS; OTOSPONGIOSIS; FRACTURES; BLIND AB Objective: To evaluate hearing outcomes in patients treated with third generation bisphosphonates for otosclerosis-related sensorineural hearing loss (SNHL). Hypothesis: Otosclerosis is a disease of abnormal bone remodeling in the otic capsule. In recent years, third generation bisphosphonates, with more powerful anti-resorptive properties and increased bone affinity, have demonstrated effectiveness in the treatment of osteoporosis and other metabolic bone diseases. We hypothesized that newer generation bisphosphonates, such as risedronate and zoledronate, would be effective in slowing the progression of SNHL in patients with otosclerosis. Study Design: Retrospective review. Setting: Tertiary referral center, ambulatory care. Interventions: Risedronate or zoledronate administration. Main Outcome Measures: Bone conduction pure tone threshold averages (PTAs) and word recognition (WR) scores were examined for each ear before and after bisphosphonate treatment. Criteria for significant change were defined as greater than 10 decibels in PTA or between 4% and 18% in WR based on binomial variance. Results: All 10 patients had audiometric progression of SNHL in the pretreatment monitoring interval and 12 ears met criteria for significant progression. All 10 patients (19 ears) showed at least no significant progression of SNHL (i.e., stabilization) at an average follow-up of 13 months. Two patients (3 ears) showed improvement by defined audiometric criteria. There were no major complications. Conclusion: Treatment with zoledronate or risedronate stabilized progressive SNHL related to otosclerosis in this small group of patients. Further evaluation of third-generation bisphosphonate treatments is warranted. C1 [Quesnel, Alicia M.; Merchant, Saumil N.; McKenna, Michael J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Quesnel, Alicia M.; Merchant, Saumil N.; Halpin, Christopher; McKenna, Michael J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Seton, Margaret] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA USA. [Halpin, Christopher] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA. RP McKenna, MJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM michael_mckenna@meei.harvard.edu FU National Institutes of Health [1R01DC009837-01A1, U24DC011943] FX This work was supported by National Institutes of Health grants 1R01DC009837-01A1 (MJM) and U24DC011943 (S. N. M.) NR 32 TC 15 Z9 15 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD OCT PY 2012 VL 33 IS 8 BP 1308 EP 1314 DI 10.1097/MAO.0b013e318268d1b3 PG 7 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 010SH UT WOS:000309113900008 PM 22935809 ER PT J AU Loggia, ML Edwards, RR Kim, J Vangel, MG Wasan, AD Gollub, RL Harris, RE Park, K Napadow, V AF Loggia, Marco L. Edwards, Robert R. Kim, Jieun Vangel, Mark G. Wasan, Ajay D. Gollub, Randy L. Harris, Richard E. Park, Kyungmo Napadow, Vitaly TI Disentangling linear and nonlinear brain responses to evoked deep tissue pain SO PAIN LA English DT Article DE Cuff pain algometry; Psychophysics; Neuroimaging; BOLD fMRI; Default mode network; Human ID PRIMARY SOMATOSENSORY CORTEX; NOXIOUS THERMAL-STIMULATION; SURFACE-BASED ANALYSIS; BLOOD-FLOW CHANGES; SINGLE-TRIAL FMRI; SELECTIVE ATTENTION; STIMULUS-INTENSITY; CORTICAL-NEURONS; NEURAL RESPONSES; CUFF ALGOMETRY AB Pain stimuli evoke widespread responses in the brain. However, our understanding of the physiological significance underlying heterogeneous response within different pain-activated and -deactivated regions is still limited. Using functional magnetic resonance imaging, we evaluated brain responses to a wide range of stimulus intensity levels (1 innocuous, 7 painful) in order to estimate region-specific stimulus-response functions, which we hypothesized could illuminate that region's functional relationship to pain. Linear and nonlinear brain responses to pain were estimated through independent Legendre polynomial transformations of pain ratings within a general linear model. This approach identified at least 5 different, regionally specific activity profiles in the brain. Linearly increasing (eg, primary somatosensory/motor cortex, insulae) and intensity-independent (eg, secondary somatosensory cortex) activation was noted in traditional pain-processing areas, potentially reflecting sensory encoding and all-or-none salience responses, respectively. Multiple activity profiles were seen in areas of the default mode network (DMN): intensity-independent deactivation (eg, posterior cingulate cortex), linearly decreasing (eg, contralateral inferior parietal lobule), and quadratic (U-shaped; eg, medial prefrontal cortex). The latter observation suggests that: (1) different DMN subregions exhibit functional heterogeneity and (2) some DMN subregions respond in a percept-related manner to pain, suggesting closer linkage between the DMN and pain processing than previously thought. Future studies should apply a similar approach using innocuous stimuli of multiple intensities to evaluate whether the response profiles reported here can also be generalized to nonpainful somatosensory processing. (C) 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Loggia, Marco L.; Edwards, Robert R.; Wasan, Ajay D.; Napadow, Vitaly] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. [Loggia, Marco L.; Gollub, Randy L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Loggia, Marco L.; Kim, Jieun; Vangel, Mark G.; Gollub, Randy L.; Park, Kyungmo; Napadow, Vitaly] MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. [Edwards, Robert R.; Wasan, Ajay D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Harris, Richard E.] Univ Michigan, Dept Anesthesiol, Chron Pain & Fatigue Res Ctr, Ann Arbor, MI 48109 USA. [Park, Kyungmo] Kyung Hee Univ, Dept Biomed Engn, Yongin, South Korea. [Napadow, Vitaly] Logan Coll Chiropract, Dept Radiol, Chesterfield, MO USA. RP Loggia, ML (reprint author), Massachusetts Gen Hosp, Bldg 120,Suite 101E, Charlestown, MA 02129 USA. EM marco@nmr.mgh.harvard.edu OI Gollub, Randy L./0000-0002-9434-4044 FU National Institutes of Health [K01-AT002166, R01-AT004714, P01-AT002048, F05-AT003770, 1K23DA020681-01A1]; National Center for Research Resources [P41RR14075, CRC 1 UL1 RR025758]; Institute of Information Technology Advancement, Korea [IITA-2008-(C1090-0801-0002)]; American College of Rheumatology; Arthritis Foundation FX We would like to thank the National Institutes of Health for funding support (V.N.: K01-AT002166, R01-AT004714, P01-AT002048; K. P.: F05-AT003770; A. W.: 1K23DA020681-01A1), the National Center for Research Resources (P41RR14075; CRC 1 UL1 RR025758, Harvard Clinical and Translational Science Center). Dr. Park was also supported by the Institute of Information Technology Advancement, Korea IITA-2008-(C1090-0801-0002). Dr. Edwards received support for this study from the American College of Rheumatology and the Arthritis Foundation. The authors would like to thank Drs. Irving Kirsch and Doug Greve for helpful comments on the manuscript. The content is solely the responsibility of the authors and does not necessarily represent the official views of our sponsors. NR 86 TC 23 Z9 23 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD OCT PY 2012 VL 153 IS 10 BP 2140 EP 2151 DI 10.1016/j.pain.2012.07.014 PG 12 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 009WG UT WOS:000309055500023 PM 22883925 ER PT J AU Dima, SO Tanase, C Albulescu, R Herlea, V Chivu-Economescu, M Purnichescu-Purtan, R Dumitrascu, T Duda, DG Popescu, I AF Dima, Simona O. Tanase, Cristiana Albulescu, Radu Herlea, Vlad Chivu-Economescu, Mihaela Purnichescu-Purtan, Raluca Dumitrascu, Traian Duda, Dan G. Popescu, Irinel TI An Exploratory Study of Inflammatory Cytokines as Prognostic Biomarkers in Patients With Ductal Pancreatic Adenocarcinoma SO PANCREAS LA English DT Article DE pancreatic ductal adenocarcinoma; inflammatory cytokines; angiogenic factors; prognostic biomarkers ID NECROSIS-FACTOR-ALPHA; STELLATE CELLS; SERUM-LEVELS; ANTIANGIOGENIC THERAPY; CANCER PATIENTS; INTERLEUKIN-8; METASTASIS; CARCINOMA; PROGRESSION; GROWTH AB Objectives: We measured the serum concentration of a panel of inflammatory cytokines and evaluated their association with circulating proangiogenic biomarkers and with outcome in patients with pancreatic ductal adenocarcinoma (PDAC). Methods: We collected serum samples from 36 patients with PDAC, 9 patients with chronic pancreatitis, and 22 healthy volunteers as a control. Inflammatory cytokines and proangiogenic biomarkers were measured using the multianalyte xMAP array and carcinoembryonic antigen (CEA) and carbohydrate 19-9 by immunoassay. Results: Patients with PDAC had higher circulating levels of interleukin 6 (IL-6) than those of patients with pancreatitis or healthy individuals and higher levels of IL-10 and tumor necrosis factor alpha (TNF-alpha) compared with those of healthy individuals. In patients with PDAC, circulating IL-6, TNF-alpha, IL-1 beta, and IL-10 correlated with serum concentrations of vascular endothelial growth factor and basic fibroblast growth factor; circulating IL-6, IL-1 beta, and TNF-alpha correlated with carbohydrate 19-9; and IL-8, IL-10, and TNF-alpha correlated with CEA levels. Circulating IL-8, TNF-alpha, and CEA; tumor stage; and lymph node metastases were associated with a poor outcome. Conclusions: The results of this exploratory study indicate that inflammatory cytokines should be pursued as potential prognostic biomarkers as well as targets for therapy in larger studies in PDAC. C1 [Dima, Simona O.; Herlea, Vlad; Dumitrascu, Traian; Popescu, Irinel] Fundeni Clin Inst, Ctr Digest Dis & Liver Transplantat, Bucharest 022328, Romania. [Tanase, Cristiana; Albulescu, Radu] Victor Babes Natl Inst Pathol, Dept Biochem & Prote, Bucharest, Romania. [Chivu-Economescu, Mihaela] Stefan S Nicolau Inst Virol, Bucharest, Romania. [Purnichescu-Purtan, Raluca] Univ Politehn Bucuresti, Dept Math, Fac Sci Appl, Bucharest, Romania. [Duda, Dan G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Popescu, I (reprint author), Fundeni Clin Inst, Ctr Digest Dis & Liver Transplantat, Sos Fundeni 258,Sect 2, Bucharest 022328, Romania. EM irinel.popescu220@gmail.com RI Chivu , Mihaela/B-4323-2011; POPESCU, IRINEL/B-3048-2008; Dima, Simona Olimpia/B-8822-2017; Tanase, Cristiana/C-2473-2011 OI Chivu , Mihaela/0000-0001-7512-4700; FU Romanian Ministry of Education-National Council for Scientific Research [PN II 41-024/2007, RU-TE100/2010, POSDRU/89/1.5/S/60746, POS CCE 685/2010] FX This study was supported by grants from the Romanian Ministry of Education-National Council for Scientific Research (PN II 41-024/2007 and RU-TE100/2010, POSDRU/89/1.5/S/60746 and POS CCE 685/2010). NR 60 TC 21 Z9 21 U1 4 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD OCT PY 2012 VL 41 IS 7 BP 1001 EP 1007 DI 10.1097/MPA.0b013e3182546e13 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 006HU UT WOS:000308810900003 PM 22722257 ER PT J AU Kida, K Minamishima, S Wang, HF Ren, JQ Yigitkanli, K Nozari, A Mandeville, JB Liu, PK Liu, CH Ichinose, F AF Kida, Kotaro Minamishima, Shizuka Wang, Huifang Ren, JiaQian Yigitkanli, Kazim Nozari, Ala Mandeville, Joseph B. Liu, Philip K. Liu, Christina H. Ichinose, Fumito TI Sodium sulfide prevents water diffusion abnormality in the brain and improves long term outcome after cardiac arrest in mice SO RESUSCITATION LA English DT Article DE Cardiac arrest; Resuscitation; Hydrogen sulfide; Magnetic resonance imaging; Matrix metalloproteinase 9; Blood brain barrier ID EMERGENCY CARDIOVASCULAR CARE; HEART-ASSOCIATION GUIDELINES; ISCHEMIA-REPERFUSION INJURY; HYDROGEN-SULFIDE; CARDIOPULMONARY-RESUSCITATION; CEREBRAL-ISCHEMIA; MATRIX METALLOPROTEINASES; MATRIX-METALLOPROTEINASE-9; HYPOTHERMIA; INHIBITION AB Aim of the study: Sudden cardiac arrest (CA) is one of the leading causes of death worldwide. Previously we demonstrated that administration of sodium sulfide (Na2S), a hydrogen sulfide (H2S) donor, markedly improved the neurological outcome and survival rate at 24 h after CA and cardiopulmonary resuscitation (CPR) in mice. In this study, we sought to elucidate the mechanism responsible for the neuroprotective effects of Na2S and its impact on the long-term survival after CA/CPR in mice. Methods: Adult male mice were subjected to potassium-induced CA for 7.5 min at 37 degrees C whereupon CPR was performed with chest compression and mechanical ventilation. Mice received Na2S (0.55 mg kg(-1) i.v.) or vehicle 1 min before CPR. Results: Mice that were subjected to CA/CPR and received vehicle exhibited a poor 10-day survival rate (4/12) and depressed neurological function. Cardiac arrest and CPR induced abnormal water diffusion in the vulnerable regions of the brain, as demonstrated by hyperintense diffusion-weighted imaging (DWI) 24 h after CA/CPR. Extent of hyperintense DWI was associated with matrix metalloproteinase 9 (MMP-9) activation, worse neurological outcomes, and poor survival rate at 10 days after CA/CPR. Administration of Na2S prevented the development of abnormal water diffusion and MMP-9 activation and markedly improved neurological function and long-term survival (9/12, P < 0.05 vs. Vehicle) after CA/CPR. Conclusion: These results suggest that administration of Na2S 1 min before CPR improves neurological function and survival rate at 10 days after CA/CPR by preventing water diffusion abnormality in the brain potentially via inhibiting MMP-9 activation early after resuscitation. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Kida, Kotaro; Minamishima, Shizuka; Nozari, Ala; Ichinose, Fumito] Massachusetts Gen Hosp, Dept Anaesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Kida, Kotaro; Minamishima, Shizuka; Wang, Huifang; Ren, JiaQian; Yigitkanli, Kazim; Nozari, Ala; Mandeville, Joseph B.; Liu, Philip K.; Liu, Christina H.; Ichinose, Fumito] Harvard Univ, Sch Med, Boston, MA USA. [Wang, Huifang; Ren, JiaQian; Yigitkanli, Kazim; Mandeville, Joseph B.; Liu, Philip K.; Liu, Christina H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Yigitkanli, Kazim] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Ichinose, F (reprint author), Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, 149 13th St,4315, Charlestown, MA 02129 USA. EM fichinose@partners.org OI Liu, Christina/0000-0002-5723-177X FU NIH [R21AT004974, DA026108, EB013768, DA029889, AHA 09GRNT2060416, HL101930, GM79360] FX This work was supported by grants from NIH R21AT004974 for Dr. Ren, DA026108, EB013768 and DA029889 (EUREKA award) and AHA 09GRNT2060416 to Dr. Liu, and NIH HL101930 and GM79360 to Dr. Ichinose. The authors thank Ikaria Inc. for generously providing IK-1001. NR 31 TC 17 Z9 20 U1 0 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-9572 J9 RESUSCITATION JI Resuscitation PD OCT PY 2012 VL 83 IS 10 BP 1292 EP 1297 DI 10.1016/j.resuscitation.2012.02.020 PG 6 WC Critical Care Medicine; Emergency Medicine SC General & Internal Medicine; Emergency Medicine GA 009UL UT WOS:000309050600033 PM 22370005 ER PT J AU Wo, JY Hong, TS Kachnic, LA AF Wo, Jennifer Y. Hong, Theodore S. Kachnic, Lisa A. TI Impact of Age and Comorbidities on the Treatment of Gastrointestinal Malignancies SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID ADVANCED PANCREATIC-CANCER; PHASE-III TRIAL; SQUAMOUS-CELL CARCINOMA; RANDOMIZED CONTROLLED-TRIAL; COMBINED-MODALITY THERAPY; ADJUVANT CHEMOTHERAPY USE; HIGH-DOSE RADIATION; ESOPHAGEAL CANCER; ELDERLY-PATIENTS; RECTAL-CANCER AB Gastrointestinal malignancies are generally considered diseases that affect older patients, with a peak in incidence in the sixth and seventh decades. Age has often been a surrogate to screen patients who may have more difficulty in tolerating treatment and the related side effects; however, chronologic age does not necessarily correlate with physiological organ impairment or poor performance status, both of which can vary substantially between individuals. Therefore, the assessment of candidacy for the ability to tolerate optimal cancer treatment should focus on the assessment of the extent of comorbidity and functional status. The review aims at providing a broad overview of the published literature regarding the tolerability and efficacy of standard treatment approaches for the most common gastrointestinal malignancies, including esophageal, pancreatic, and colorectal cancer, among elderly patients. Semin Radiat Oncol 22:311-320 (C) 2012 Elsevier Inc. All rights reserved. C1 [Wo, Jennifer Y.; Hong, Theodore S.; Kachnic, Lisa A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Kachnic, Lisa A.] Boston Univ, Sch Med, Boston Med Ctr, Dept Radiat Oncol, Boston, MA 02118 USA. RP Wo, JY (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox Pharmaceut 3, Boston, MA 02114 USA. EM jwo@partners.org NR 81 TC 7 Z9 7 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1053-4296 EI 1532-9461 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD OCT PY 2012 VL 22 IS 4 BP 311 EP 320 DI 10.1016/j.semradonc.2012.05.008 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 013HK UT WOS:000309296300008 PM 22985814 ER PT J AU Luo, YC Dallaglio, K Chen, Y Robinson, WA Robinson, SE McCarter, MD Wang, JB Gonzalez, R Thompson, DC Norris, DA Roop, DR Vasiliou, V Fujita, M AF Luo, Yuchun Dallaglio, Katiuscia Chen, Ying Robinson, William A. Robinson, Steven E. McCarter, Martin D. Wang, Jianbin Gonzalez, Rene Thompson, David C. Norris, David A. Roop, Dennis R. Vasiliou, Vasilis Fujita, Mayumi TI ALDH1A Isozymes are Markers of Human Melanoma Stem Cells and Potential Therapeutic Targets SO STEM CELLS LA English DT Article DE Melanoma; Cancer stem cells; Tumor-initiating cells; Aldehyde dehydrogenase; Microarray analysis; Molecular targeted therapy ID ALDEHYDE DEHYDROGENASE-ACTIVITY; INITIATING CELLS; PHASE-II; METASTATIC MELANOMA; FUNCTIONAL MARKER; BREAST-CANCER; LUNG-CANCER; IDENTIFICATION; CD133; CHEMOTHERAPY AB Although the concept of cancer stem cells (CSCs) is well-accepted for many tumors, the existence of such cells in human melanoma has been the subject of debate. In this study, we demonstrate the existence of human melanoma cells that fulfill the criteria for CSCs (self-renewal and differentiation) by serially xenotransplanting cells into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. These cells possess high aldehyde dehydrogenase (ALDH) activity with ALDH1A1 and ALDH1A3 being the predominant ALDH isozymes. ALDH-positive melanoma cells are more tumorigenic than ALDH-negative cells in both NOD/SCID mice and NSG mice. Biological analyses of the ALDH-positive melanoma cells reveal the ALDH isozymes to be key molecules regulating the function of these cells. Silencing ALDH1A by siRNA or shRNA leads to cell cycle arrest, apoptosis, decreased cell viability in vitro, and reduced tumorigenesis in vivo. ALDH-positive melanoma cells are more resistant to chemotherapeutic agents and silencing ALDH1A by siRNA sensitizes melanoma cells to drug-induced cell death. Furthermore, we, for the first time, examined the molecular signatures of ALDH-positive CSCs from patient-derived tumor specimens. The signatures of melanoma CSCs include retinoic acid (RA)-driven target genes with RA response elements and genes associated with stem cell function. These findings implicate that ALDH isozymes are not only biomarkers of CSCs but also attractive therapeutic targets for human melanoma. Further investigation of these isozymes and genes will enhance our understanding of the molecular mechanisms governing CSCs and reveal new molecular targets for therapeutic intervention of cancer. STEM Cells2012;30:21002113 C1 [Luo, Yuchun; Dallaglio, Katiuscia; Norris, David A.; Roop, Dennis R.; Fujita, Mayumi] Univ Colorado Denver, Dept Dermatol, Aurora, CO 80045 USA. [Dallaglio, Katiuscia; Roop, Dennis R.; Fujita, Mayumi] Univ Colorado Denver, Charles C Gates Ctr Regenerat Med & Stem Cell Bio, Aurora, CO 80045 USA. [Chen, Ying; Vasiliou, Vasilis] Univ Colorado Denver, Dept Pharmaceut Sci, Aurora, CO 80045 USA. [Robinson, William A.; Robinson, Steven E.; Gonzalez, Rene] Univ Colorado Denver, Div Med Oncol, Dept Med, Aurora, CO 80045 USA. [McCarter, Martin D.] Univ Colorado Denver, Dept Surg, Aurora, CO 80045 USA. [Wang, Jianbin] Univ Colorado Denver, Dept Biochem & Mol Genet, Aurora, CO 80045 USA. [Norris, David A.; Fujita, Mayumi] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Fujita, M (reprint author), Univ Colorado Denver, Dept Dermatol, Mail Stop 8127,12801 E 17th Ave,Rm 4124, Aurora, CO 80045 USA. EM mayumi.fujita@ucdenver.edu RI Luo, Yuchun/B-8683-2014; Wang, Jianbin/B-8973-2016 OI Wang, Jianbin/0000-0003-3155-894X FU NIH [CA125833]; Veterans Affairs Merit Review Award; UCCC; Wendy Will Case Cancer Fund; Tadamitsu Cancer Research Fund; NEI [EY11490, EY17963] FX We thank the University of Colorado Denver melanoma tissue bank for providing human melanoma samples, the University of Colorado Cancer Center (UCCC) flow core (Alistaire S. Acosta and Karen Helm) for helping with FACS sorting, the Mind Research Network from New Mexico (Marilee Morgan and Kent Hutchison) for helping with microarray analysis, and Garrick Talmage for assisting with experiments. We also thank Miki Tanioka, M. D., Ph.D. (Department of Dermatology, Kyoto University) and J Daniel Jensen, M. D. (Sacred Heart Medical Center from Spokane, WA) for critically reviewing the manuscript. This work was supported by an NIH Grant CA125833 (to M. F.), Veterans Affairs Merit Review Award (to M. F.), a grant from the UCCC (to M. F.), Wendy Will Case Cancer Fund (to M. F.), Tadamitsu Cancer Research Fund (to M. F.), and NEI Grants EY17963 and EY11490 (to V.V.). NR 53 TC 83 Z9 84 U1 2 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD OCT PY 2012 VL 30 IS 10 BP 2100 EP 2113 DI 10.1002/stem.1193 PG 14 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 008AA UT WOS:000308928300004 PM 22887839 ER PT J AU Mutabaruka, J Sejourne, N Bui, E Birmes, P Chabrol, H AF Mutabaruka, Jean Sejourne, Nathalene Bui, Eric Birmes, Philippe Chabrol, Henri TI Traumatic Grief and Traumatic Stress in Survivors 12?Years after the Genocide in Rwanda SO STRESS AND HEALTH LA English DT Article DE complicated grief; PTSD; trauma ID PERITRAUMATIC DISTRESS INVENTORY; BEREAVEMENT-RELATED DEPRESSION; MOTOR-VEHICLE ACCIDENT; COMPLICATED GRIEF; INDUSTRIAL DISASTER; DISORDER DISTINCT; CHILDREN VICTIMS; PTSD; SYMPTOMS; VALIDATION AB The relationship between exposure to traumatic events and traumatic grief and the role of mediating and moderating variables [peritraumatic distress, post traumatic stress disorder (PTSD) symptoms and symptoms of depression] were studied in survivors of the genocide of Batutsi in Rwanda in 1994. One hundred and two survivors (70 women, mean age 45?+/-?7.53?years) participated in this retrospective study. All of them had lost a member of their family. The severity of traumatic exposure (Comprehensive Trauma Inventory), peritraumatic distress (Peritraumatic Distress Inventory), current PTSD symptoms (PTSD Checklist), depressive symptoms (Beck Depression Inventory) and traumatic grief symptoms (Inventory of Traumatic Grief) was evaluated. A hierarchical multiple regression analysis was then conducted to examine the relative contribution of each variable to the symptoms of traumatic grief. The severity of traumatic exposure was related to traumatic grief symptoms (B?=?0.06, R?=?0.6, R2?=?0.36 and beta?=?0.6, t?=?7.54, p?=?0.00). The Baron and Kenny procedure (1986) (including three separate regressions), along with the Sobel test, was used to test mediation effects. Peritraumatic distress and PTSD symptoms may be mediating variables between traumatic exposure and traumatic grief. Traumatic grief is a complex but assessable entity, where previous distress and suffering result from both psychological trauma and the loss of a loved one. Copyright (c) 2011 John Wiley & Sons, Ltd. C1 [Birmes, Philippe] Univ Toulouse, UPS, CHU Toulouse, Hop Casselardit,LST,EA 4560, F-31059 Toulouse 9, France. [Mutabaruka, Jean; Sejourne, Nathalene; Chabrol, Henri] Univ Toulouse, Ctr Etud & Rech Psychopathol, F-31059 Toulouse 9, France. [Bui, Eric] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bui, Eric] Harvard Univ, Sch Med, Boston, MA USA. RP Birmes, P (reprint author), Univ Toulouse, UPS, CHU Toulouse, Hop Casselardit,LST,EA 4560, 170 Av Casselardit,TSA 40031, F-31059 Toulouse 9, France. EM birmes.p@chu-toulouse.fr RI Bui, Eric/J-8347-2015 OI Bui, Eric/0000-0002-1413-6473 NR 49 TC 2 Z9 2 U1 0 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1532-3005 J9 STRESS HEALTH JI Stress Health PD OCT PY 2012 VL 28 IS 4 BP 289 EP 296 DI 10.1002/smi.1429 PG 8 WC Psychology, Applied; Psychiatry; Psychology SC Psychology; Psychiatry GA 011RR UT WOS:000309183000004 PM 22282057 ER PT J AU Tjarnlund-Wolf, A Brogren, H Lo, EH Wang, XY AF Tjarnlund-Wolf, Anna Brogren, Helen Lo, Eng H. Wang, Xiaoying TI Plasminogen Activator Inhibitor-1 and Thrombotic Cerebrovascular Diseases SO STROKE LA English DT Article DE fibrinolysis; plasminogen activator inhibitor-1; stroke; thrombotic cerebrovascular diseases ID BETA-INDUCIBLE ELEMENTS; ISCHEMIC BRAIN-INJURY; METABOLIC SYNDROME; MULTICENTER EVALUATION; INSULIN-RESISTANCE; DIABETES-MELLITUS; ENDOTHELIAL-CELLS; HUMAN ASTROCYTES; STROKE PATIENTS; HEART-DISEASE C1 [Tjarnlund-Wolf, Anna; Lo, Eng H.; Wang, Xiaoying] Harvard Univ, Dept Neurol, Neuroprotect Res Lab, Massachusetts Gen Hosp,Med Sch, Charlestown, MA 02129 USA. [Tjarnlund-Wolf, Anna; Lo, Eng H.; Wang, Xiaoying] Harvard Univ, Dept Radiol, Neuroprotect Res Lab, Massachusetts Gen Hosp,Med Sch, Charlestown, MA 02129 USA. [Tjarnlund-Wolf, Anna] Univ Gothenburg, Sahlgrenska Acad, Sect Clin Neurosci & Rehabil, Inst Neurosci & Physiol, Gothenburg, Sweden. [Brogren, Helen] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Wallenberg Lab Cardiovasc Res, Gothenburg, Sweden. RP Wang, XY (reprint author), Harvard Univ, Dept Neurol, Neuroprotect Res Lab, Massachusetts Gen Hosp,Med Sch, 149 13th St,Room 2411A, Charlestown, MA 02129 USA. EM wangxi@helix.mgh.harvard.edu FU Swedish Research Council [524-2011-7563]; Swedish Society of Medicine; Goteborg Foundation for Neurological Research; Rune and Ulla Amlov Foundation; Edit Jacobson Foundation; Ake Wiberg Foundation; Swedish Heart-Lung Foundation; Magn Bergvalls Foundation; National Institute of Health [R37-NS37074, R01-NS065998] FX The present study was supported in part by the Swedish Research Council (grant 524-2011-7563), the Swedish Society of Medicine, the Goteborg Foundation for Neurological Research, the Rune and Ulla Amlov, Edit Jacobson and Ake Wiberg Foundations (to A.T.-W.); the Swedish Heart-Lung Foundation and Magn Bergvalls Foundation (to B. H.); National Institute of Health grants R37-NS37074 (to E. H. L.) and R01-NS065998 (to X.W.). NR 71 TC 24 Z9 24 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 2012 VL 43 IS 10 BP 2833 EP 2839 DI 10.1161/STROKEAHA.111.622217 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 012TG UT WOS:000309258900061 PM 22879095 ER PT J AU Ross, S Rosemurgy, A Albrink, M Choung, E Dapri, G Gallagher, S Hernandez, J Horgan, S Kelley, W Kia, M Marks, J Martinez, J Mintz, Y Oleynikov, D Pryor, A Rattner, D Rivas, H Roberts, K Rubach, E Schwaitzberg, S Swanstrom, L Sweeney, J Wilson, E Zemon, H Zundel, N AF Ross, Sharona Rosemurgy, Alexander Albrink, Michael Choung, Edward Dapri, Giovanni Gallagher, Scott Hernandez, Jonathan Horgan, Santiago Kelley, William Kia, Michael Marks, Jeffrey Martinez, Jose Mintz, Yoav Oleynikov, Dmitry Pryor, Aurora Rattner, David Rivas, Homero Roberts, Kurt Rubach, Eugene Schwaitzberg, Steven Swanstrom, Lee Sweeney, John Wilson, Erik Zemon, Harry Zundel, Natan TI Consensus statement of the consortium for LESS cholecystectomy SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article DE Cholecystectomy; LESS; Laparoendoscopic single site ID LAPAROENDOSCOPIC SINGLE-SITE; LAPAROSCOPIC CHOLECYSTECTOMY; PORT CHOLECYSTECTOMY; SAFE AB Many surgeons attempting Laparo-Endoscopic Single Site (LESS) cholecystectomy have found the operation difficult, which is inconsistent with our experience. This article is an attempt to promote a standardized approach that we feel surgeons with laparoscopic skills can perform safely and efficiently. This is a four-trocar approach consistent with the four incisions utilized in conventional laparoscopic cholecystectomy. After administration of general anesthesia, marcaine is injected at the umbilicus and a 12-mm vertical incision is made through the already existing anatomical scar of the umbilicus. A single four-trocar port is inserted. A 5-mm deflectable-tip laparoscope is placed through the trocar at the 8 o'clock position, a bariatric length rigid grasper is inserted through the trocar at the 4 o'clock position (to grasp the fundus), and a rigid bent grasper is placed through the 10-mm port (to grasp the infundibulum). This arrangement of the instruments promotes minimal internal and external instrument clashing with simultaneous optimization of the operative view. This orientation allows retraction of the gallbladder in a cephalad and lateral direction, development of a window between the gallbladder and the liver which promotes the "critical view" of the cystic duct and artery, and provides triangulation with excellent visualization of the operative field. The operation is concluded with diaphragmatic irrigation of marcaine solution to minimize postoperative pain. Standardization of LESS cholecystectomy will speed adoption, reduce intraoperative complications, and improve the efficiency and safety of the approach. C1 [Ross, Sharona; Rosemurgy, Alexander] Florida Hosp Tampa, HPB & Foregut Adv Laparoscop & Robot Surg, Tampa, FL 33613 USA. [Albrink, Michael] Univ S Florida, Tampa Gen Hosp, Dept Gen Surg, Coll Med, Tampa, FL 33606 USA. [Choung, Edward] Tampa Gen Hosp, Tampa Gen Med Grp, Dept Surg, Tampa, FL 33606 USA. [Dapri, Giovanni] Hop Univ St Pierre, Dept Gastrointestinal Surg, B-1000 Brussels, Belgium. [Gallagher, Scott] Forsyth Med Ctr, Dept Surg, Winston Salem, NC 27103 USA. [Hernandez, Jonathan] Univ S Florida, Coll Med, Dept Gen Surg, Tampa, FL USA. [Horgan, Santiago] UC San Diego Med Ctr, Div Minimally Invas Surg, San Diego, CA USA. [Kelley, William] HCA Virginia Hlth Syst, Richmond Surg, Dept Gen Surg, Richmond, VA USA. [Kia, Michael] McLaren Flint Reg Med Ctr, Flint, MI 48532 USA. [Marks, Jeffrey] Univ Hosp Case Med Ctr, Dept Surg, Cleveland, OH USA. [Martinez, Jose] Univ Miami, Miller Sch Med, Dept Surg, Miami, FL 33136 USA. [Mintz, Yoav] Hebrew Univ Jerusalem, Med Ctr, Dept Surg, Jerusalem, Israel. [Oleynikov, Dmitry] Univ Nebraska Med Ctr, Dept Surg, Omaha, NE 68198 USA. [Pryor, Aurora] SUNY Stony Brook, Dept Surg, Div Gen Surg, Med Ctr, Stony Brook, NY 11794 USA. [Rattner, David] Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. [Rivas, Homero] Stanford Univ, Sch Med, Dept Surg, Palo Alto, CA 94304 USA. [Roberts, Kurt] Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA. [Rubach, Eugene] St Francis Hosp, Manhasset, NY 11030 USA. [Schwaitzberg, Steven] Cambridge Hlth Alliance, Dept Surg, Cambridge, MA USA. [Swanstrom, Lee] Oregon Clin, Portland, OR 97213 USA. [Sweeney, John] Emory Univ Hosp, Dept Surg, Atlanta, GA 30322 USA. [Wilson, Erik] Univ Texas Houston, Med Sch Houston, Dept Surg, Houston, TX 77030 USA. [Zemon, Harry] Northshore Long Isl Jewish Univ Hosp, Dept Surg, Hyde Pk, NY 11040 USA. [Zundel, Natan] Florida Int Univ, Coll Med, Miami, FL 33199 USA. RP Ross, S (reprint author), Florida Hosp Tampa, HPB & Foregut Adv Laparoscop & Robot Surg, 3100 E Fletcher Ave,Suite 310, Tampa, FL 33613 USA. EM sharona.ross@yahoo.com RI Roberts, Kurt/I-2226-2012; OI Oleynikov, Dmitry/0000-0002-0656-6596 FU Virtual Ports; EasyLap; EasyNotes; Eon Surgical; Silenseed; MST; Lumenis; Ethicon Endo-Surgery; Storz Endoscopy; Olympus; Johnson Johnson; Covidien FX Sharona Ross, MD, is a consultant for Covidien and Olympus. Alex Rosemurgy, MD, is a consultant for Covidien and Olympus. Santiago Horgan, MD, is a stockholder for USGI, Apollo, Valentx, Virtual Ports, and Eon Surgical. Dr. Horgan is also a speaker for Ethicon Endo-Surgery, Stryker, Intuitive, Olympus, and Gore. William Kelley, MD, has been a speaker for Covidien and is on the scientific advisory board for TransEnterics with some stock options. Michael Kia, MD, is a consultant for Olympus, Ethicon, and Cardinal. Jeffrey Marks, MD, is a consultant for Covidien, Olympus, and Gore. Dr. Marks is also on the advisory council for Apollo Endosurgery. Jose Martinez, MD, has received honoraria from Boston Scientific, Olympus, and Lifecell. Yoav Mintz, MD, is a consultant and receives consulting fees from Virtual Ports, EasyLap, EasyNotes, Eon Surgical, Silenseed, MST, and Lumenis. Dr. Mintz also received an educational grant from Ethicon Endo-Surgery and Storz Endoscopy. Dr. Aurora Pryor, MD, is a consultant with Olympus and Gore, in addition to being a speaker for Covidien. Dr. Pryor also has ownership interest with Transenterix and Barosense. David Rattner, MD, is a consultant with Olympus and is on the scientific advisory board with Transenterix. Homero Rivas, MD, has been a lecturer for Covidien. Kurt Roberts, MD, is a consultant for and receives consulting fees from Olympus. Dr. Roberts also have ownership interest with NovaTract. Eugene Rubach, MD, is a consultant for and holds a research grant with Johnson & Johnson, a research grant with Covidien, and is a speaker with Gore. Steven Schwaitzberg, MD, is a consultant with Endocore, Olympus, Stryker, Surgiquest, Neatstitch, Combridge Endo, and Acuity Bio. Erik Wilson, MD, has taught at, proctored at, and consulted with Ethicon Endo, Intuitive Surgical, Gore, and Olympus. Harry Zemon, MD, is a consultant with Olympus, and Nathan Zundel, MD, is a consultant with Olympus, Covidien, Apollo, and Ethicon. In addition, Dr. Zundel is a speaker for Ethicon and CibeMed. Michael Albrink, MD, Edward Choung, MD, Giovanni Dapri, MD, Scott Gallagher, MD, Jonathan Hernandez, MD, Dmitry Oleynikov, MD, Lee Swanstrom, MD, and John Sweeney, MD, have no conflicts of interest or financial ties to disclose. NR 13 TC 21 Z9 24 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD OCT PY 2012 VL 26 IS 10 BP 2711 EP 2716 DI 10.1007/s00464-012-2478-y PG 6 WC Surgery SC Surgery GA 011OR UT WOS:000309175200002 PM 22936433 ER PT J AU Makar, RS Powers, A Stowell, CP AF Makar, Robert S. Powers, Amy Stowell, Christopher P. TI Reducing Transfusion-Related Acute Lung Injury Risk: Evidence for and Approaches to Transfusion-Related Acute Lung Injury Mitigation SO TRANSFUSION MEDICINE REVIEWS LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; PULMONARY HYPERSENSITIVITY REACTION; RESPIRATORY-DISTRESS-SYNDROME; BRAIN NATRIURETIC PEPTIDE; WHITE CELL-REDUCTION; AMERICAN-RED-CROSS; BLOOD-DONORS; LEUKOCYTE ANTIBODIES; CIRCULATORY OVERLOAD; CONSENSUS CONFERENCE AB Transfusion-related acute lung injury (TRALI) is a major cause of transfusion-related morbidity and mortality. Although the pathogenesis of TRALI is incompletely understood, substantial data from hemovigilance systems, large case series, clinical trials, and animal models have identified antileukocyte antibodies as a major precipitant and have contributed to the development of concrete interventions to reduce the risk of TRALI. This review presents the clinical data supporting specific donor management strategies to reduce TRALI risk and their observed clinical efficacy. Novel strategies that use the donor health questionnaire combined with testing are discussed, and important challenges that remain going forward are explored. (C) 2012 Elsevier Inc. All rights reserved. C1 [Makar, Robert S.] Massachusetts Gen Hosp, Blood Transfus Serv, Dept Pathol, Boston, MA 02114 USA. Queens Med Ctr, Dept Pathol, Honolulu, HI USA. RP Makar, RS (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, Dept Pathol, 55 Fruit St,GRJ-2-206C, Boston, MA 02114 USA. EM rmakar@partners.org NR 84 TC 6 Z9 6 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0887-7963 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD OCT PY 2012 VL 26 IS 4 BP 305 EP 320 DI 10.1016/j.tmrv.2012.03.001 PG 16 WC Hematology SC Hematology GA 013GY UT WOS:000309295100002 PM 22520553 ER PT J AU Janoff, EN Gustafson, C Frank, DN AF Janoff, Edward N. Gustafson, Claire Frank, Daniel N. TI The world within: living with our microbial guests and guides SO TRANSLATIONAL RESEARCH LA English DT Editorial Material ID INFLAMMATORY-BOWEL-DISEASE; INTESTINAL MICROBIOTA; GUT MICROBIOTA; COMMENSAL BACTERIA; IMMUNE-RESPONSES; DENDRITIC CELLS; INDUCTION; IGA; ENVIRONMENT; MICROFLORA C1 [Janoff, Edward N.] Univ Colorado Denver, Sch Med, Div Infect Dis, Dept Med, Aurora, CO 80045 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Univ Colorado Denver, Sch Med, Microbiome Res Consortium, Aurora, CO USA. RP Janoff, EN (reprint author), Univ Colorado Denver, Sch Med, Div Infect Dis, Dept Med, 12700 E 19th Ave,Box B-168, Aurora, CO 80045 USA. EM Edward.Janoff@ucdenver.edu FU NHGRI NIH HHS [R21HG005964]; NIAID NIH HHS [R21 AI083615, R21AI083615]; NICHD NIH HHS [R01 HD059527, R01HD059527] NR 47 TC 6 Z9 6 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1931-5244 J9 TRANSL RES JI Transl. Res. PD OCT PY 2012 VL 160 IS 4 BP 239 EP 245 DI 10.1016/j.trsl.2012.05.005 PG 7 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA 013IM UT WOS:000309299100001 PM 22732305 ER PT J AU Tomblyn, M Chen, M Kukreja, M Aljurf, MD Al Mohareb, F Bolwell, BJ Cahn, JY Carabasi, MH Gale, RP Gress, RE Gupta, V Hale, GA Ljungman, P Maziarz, RT Storek, J Wingard, JR Young, JAH Horowitz, MM Ballen, KK AF Tomblyn, M. Chen, M. Kukreja, M. Aljurf, M. D. Al Mohareb, F. Bolwell, B. J. Cahn, J. -Y. Carabasi, M. H. Gale, R. P. Gress, R. E. Gupta, V. Hale, G. A. Ljungman, P. Maziarz, R. T. Storek, J. Wingard, J. R. Young, J. -A. H. Horowitz, M. M. Ballen, K. K. TI No increased mortality from donor or recipient hepatitis B- and/or hepatitis C-positive serostatus after related-donor allogeneic hematopoietic cell transplantation SO TRANSPLANT INFECTIOUS DISEASE LA English DT Article DE allogeneic transplantation; hepatitis B; hepatitis C ID BONE-MARROW-TRANSPLANTATION; VIRUS-INFECTION; SURFACE-ANTIGEN; VIRAL REACTIVATION; HOST DISEASE; FOLLOW-UP; LAMIVUDINE; LIVER; RISK; THERAPY AB Limited data exist on allogeneic transplant outcomes in recipients receiving hematopoietic cells from donors with prior or current hepatitis B (HBV) or C virus (HCV) infection (seropositive donors), or for recipients with prior or current HBV or HCV infection (seropositive recipients). Transplant outcomes are reported for 416 recipients from 121 centers, who received a human leukocyte antigen-identical related-donor allogeneic transplant for hematologic malignancies between 1995 and 2003. Of these, 33 seronegative recipients received grafts from seropositive donors and 128 recipients were seropositive. The remaining 256 patients served as controls. With comparable median follow-up (cases, 5.9 years; controls, 6.7 years), the incidence of treatment-related mortality, survival, graft-versus-host disease, and hepatic toxicity, appears similar in all cohorts. The frequencies of hepatic toxicities as well as causes of death between cases and controls were similar. Prior exposure to HBV or HCV in either the donor or the recipient should not be considered an absolute contraindication to transplant. C1 [Tomblyn, M.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Tomblyn, M.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplantat, Milwaukee, WI 53226 USA. [Chen, M.; Kukreja, M.; Horowitz, M. M.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Aljurf, M. D.; Al Mohareb, F.] King Faisal Specialist Hosp & Res Ctr, Riyadh 11211, Saudi Arabia. [Bolwell, B. J.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Cahn, J. -Y.] CHU Grenoble, Hop A Michallon, Serv Hematol, F-38043 Grenoble, France. [Carabasi, M. H.] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. [Gale, R. P.] Celgene Corp, Clin Res, Summit, NJ USA. [Gress, R. E.] NIH, Bethesda, MD 20892 USA. [Gupta, V.] Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. [Hale, G. A.] Univ S Florida, All Childrens Hosp, Blood & Marrow Transplant Program, St Petersburg, FL 33701 USA. [Ljungman, P.] Karolinska Univ Hosp, Karolinska Inst, Ctr Allogene Stem Cell Transplantat, Stockholm, Sweden. [Maziarz, R. T.] Oregon Hlth & Sci Univ, Ctr Hematol Malignancies, Portland, OR 97201 USA. [Storek, J.] Univ Calgary, Tom Baker Canc Ctr, Bone Marrow Transplant Program, Calgary, AB T2N 1N4, Canada. [Wingard, J. R.] Univ Florida, Shands Hosp, Gainesville, FL USA. [Young, J. -A. H.] Univ Minnesota, Masonic Canc Ctr, Clin Trials Off, Minneapolis, MN USA. [Ballen, K. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Tomblyn, M (reprint author), 12902 Magnolia Dr,FOB 3, Tampa, FL 33612 USA. EM marcie.tomblyn@moffitt.org RI Young, Jo-Anne/G-2617-2013; Cahn, Jean-Yves/M-6493-2014 OI Young, Jo-Anne/0000-0003-4182-341X; FU Public Health Service from the National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases (NIAID); NHLBI [5U01HL069294]; NCI; Health Resources and Services Administration (HRSA/DHHS); Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; AABB; Aetna; American Society for Blood and Marrow Transplantation; Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Astellas Pharma US, Inc.; Baxter International, Inc.; Bayer HealthCare Pharmaceuticals; Be the Match Foundation; Biogen IDEC; BioMarin Pharmaceutical, Inc.; Biovitrum AB; Blood-Center of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Buchanan Family Foundation; Canadian Blood and Marrow Transplant Group; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Centers for Disease Control and Prevention; Children's Leukemia Research Association; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Cubist Pharmaceuticals; Cylex Inc.; CytoTherm; DOR BioPharma, Inc.; Dynal Biotech; Invitrogen Company; Eisai, Inc.; Enzon Pharmaceuticals, Inc.; European Group for Blood and Marrow Transplantation; Gamida Cell, Ltd.; GE Healthcare; Genentech, Inc.; Genzyme Corporation; Histogenetics, Inc.; HKS Medical Information Systems; Hospira, Inc.; Infectious Diseases Society of America; Kiadis Pharma; Kirin Brewery Co., Ltd.; Leukemia & Lymphoma Society; Merck Company; Medical College of Wisconsin; MGI Pharma, Inc.; Michigan Community Blood Centers; Millennium Pharmaceuticals, Inc.; Miller Pharmacal Group; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Nature Publishing Group; New York Blood Center; Novartis Oncology; Oncology Nursing Society; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Pall Life Sciences; Pfizer Inc; Saladax Biomedical, Inc.; Schering Corporation; Society for Healthcare Epidemiology of America; Soligenix, Inc.; StemCyte, Inc.; StemSoft Software, Inc.; Sysmex America, Inc.; THER-AKOS, Inc.; Thermogenesis Corporation; Vidacare Corporation; Vion Pharmaceuticals, Inc.; ViraCor Laboratories; ViroPharma, Inc.; Wellpoint, Inc.; [HHSH234200637015C] FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI; a contract HHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from AABB; Aetna; American Society for Blood and Marrow Transplantation; Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Astellas Pharma US, Inc.; Baxter International, Inc.; Bayer HealthCare Pharmaceuticals; Be the Match Foundation; Biogen IDEC; BioMarin Pharmaceutical, Inc.; Biovitrum AB; Blood-Center of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Buchanan Family Foundation; Canadian Blood and Marrow Transplant Group; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Centers for Disease Control and Prevention; Children's Leukemia Research Association; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Cubist Pharmaceuticals; Cylex Inc.; CytoTherm; DOR BioPharma, Inc.; Dynal Biotech, an Invitrogen Company; Eisai, Inc.; Enzon Pharmaceuticals, Inc.; European Group for Blood and Marrow Transplantation; Gamida Cell, Ltd.; GE Healthcare; Genentech, Inc.; Genzyme Corporation; Histogenetics, Inc.; HKS Medical Information Systems; Hospira, Inc.; Infectious Diseases Society of America; Kiadis Pharma; Kirin Brewery Co., Ltd.; The Leukemia & Lymphoma Society; Merck & Company; The Medical College of Wisconsin; MGI Pharma, Inc.; Michigan Community Blood Centers; Millennium Pharmaceuticals, Inc.; Miller Pharmacal Group; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Nature Publishing Group; New York Blood Center; Novartis Oncology; Oncology Nursing Society; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Pall Life Sciences; Pfizer Inc; Saladax Biomedical, Inc.; Schering Corporation; Society for Healthcare Epidemiology of America; Soligenix, Inc.; StemCyte, Inc.; StemSoft Software, Inc.; Sysmex America, Inc.; THER-AKOS, Inc.; Thermogenesis Corporation; Vidacare Corporation; Vion Pharmaceuticals, Inc.; ViraCor Laboratories; ViroPharma, Inc.; and Wellpoint, Inc. NR 30 TC 5 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-2273 J9 TRANSPL INFECT DIS JI Transpl. Infect. Dis. PD OCT PY 2012 VL 14 IS 5 BP 468 EP 478 DI 10.1111/j.1399-3062.2012.00732.x PG 11 WC Immunology; Infectious Diseases; Transplantation SC Immunology; Infectious Diseases; Transplantation GA 012ME UT WOS:000309239500020 PM 22548788 ER PT J AU Richter, JM Barrett, J Oster, G AF Richter, J. M. Barrett, J. Oster, G. TI Letter: real-life management of new onset ulcerative colitis and proctitis - authors' reply SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article C1 [Richter, J. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Richter, J. M.] Harvard Univ, Sch Med, Boston, MA USA. [Oster, G.] Policy Anal Inc, Brookline, MA USA. RP Richter, JM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM goster@pai2.com NR 2 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD OCT PY 2012 VL 36 IS 7 BP 686 EP 686 DI 10.1111/apt.12024 PG 1 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 003TB UT WOS:000308633100016 ER PT J AU Bangalore, S Fonarow, GC Peterson, ED Hellkamp, AS Hernandez, AF Laskey, W Peacock, WF Cannon, CP Schwamm, LH Bhatt, DL AF Bangalore, Sripal Fonarow, Gregg C. Peterson, Eric D. Hellkamp, Anne S. Hernandez, Adrian F. Laskey, Warren Peacock, W. Frank Cannon, Christopher P. Schwamm, Lee H. Bhatt, Deepak L. CA Get Guidelines Steering Comm Inves TI Age and Gender Differences in Quality of Care and Outcomes for Patients with ST-segment Elevation Myocardial Infarction SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Gender; Myocardial infarction; Prognosis; Young ID ACUTE CORONARY SYNDROMES; YOUNG-PATIENTS; ANGIOGRAPHIC FEATURES; RISK-FACTORS; SEX-DIFFERENCES; WOMEN; EXPERIENCE; MEN; VARIABLES; REGISTRY AB BACKGROUND: Young patients (aged <= 45 years) presenting with ST-segment elevation myocardial infarction present unique challenges. The quality of care and in-hospital outcomes may differ from their older counterparts. METHODS: A total of 31,544 patients presenting with ST-segment elevation myocardial infarction and enrolled in the American Heart Association's Get With the Guidelines Coronary Artery Disease registry were analyzed. The cohort was divided into those aged 45 years or less and those aged more than 45 years. RESULTS: Young patients accounted for 10.3% of all ST-segment elevation myocardial infarction cases. Compared with older patients, younger patients were less likely to have traditional cardiovascular risk factors and had similar or better quality/performance measures with lower in-hospital mortality (unadjusted rate 1.6 vs 6.5%, P < .0001; adjusted odds ratio [OR], 0.37; 95% confidence interval [CI], 0.29-0.46). Time trend analysis (2002-2008) suggested an increase over time in the "all or none" composite performance measure in both the younger and older patients (68%-97% and 69%-96%, respectively). However, there was significantly lower quality of care and worse outcomes in women (vs men) and in the very young (<= 35 vs 36-45 years). Significant interaction was seen between age and gender for in-hospital death, such that the gender difference was greater in the younger cohort. Similar interaction was seen for door-to-thrombolytic time such that the gender delay was greater in the younger cohort (women: men ratio of means = 1.73, 95% CI, 1.21-2.45 [younger] vs 1.08, 95% CI, 1.00-1.18 [older]; P interaction = .0031). CONCLUSION: Young patients aged 45 years or less presenting with ST-segment elevation myocardial infarction overall had similar quality of care and in-hospital outcomes as older counterparts. However, quality of care was significantly lower and mortality was higher in young women (vs young men) and the very young (<= 35 vs 36-45 years). (c) 2012 Elsevier Inc. All rights reserved. circle The American Journal of Medicine (2012) 125, 1000-1009 C1 [Bangalore, Sripal] NYU, Sch Med, Cardiac Catheterizat Lab, Leon H Charney Div Cardiol,Med Ctr, New York, NY 10016 USA. [Fonarow, Gregg C.] Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA. [Peterson, Eric D.; Hellkamp, Anne S.; Hernandez, Adrian F.] Duke Clin Res Inst, Durham, NC USA. [Laskey, Warren] Univ New Mexico, Albuquerque, NM 87131 USA. [Peacock, W. Frank] Cleveland Clin, Cleveland, OH 44106 USA. [Cannon, Christopher P.] TIMI Study Grp, Boston, MA USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. RP Bangalore, S (reprint author), NYU, Sch Med, Cardiac Catheterizat Lab, Leon H Charney Div Cardiol,Med Ctr, New York, NY 10016 USA. EM sripal.bangalore@nyumc.org RI Bangalore, Sripal/B-6246-2013; Hernandez, Adrian F./A-7818-2016; OI Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616; Bangalore, Sripal/0000-0001-9485-0652 FU American Heart Association Pharmaceutical Roundtable; Merck FX The Get With The Guidelines-Coronary Artery Disease (GWTG-CAD) program was provided by the American Heart Association. The GWTG-CAD program was supported in part through the American Heart Association Pharmaceutical Roundtable and an unrestricted educational grant from Merck. NR 26 TC 35 Z9 35 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT PY 2012 VL 125 IS 10 BP 1000 EP 1009 DI 10.1016/j.amjmed.2011.11.016 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 010UR UT WOS:000309120400030 PM 22748404 ER PT J AU Baker, JF Mehta, NN Baker, DG Toedter, G Shults, J Von Feldt, JM Leonard, MB AF Baker, Joshua F. Mehta, Nehal N. Baker, Daniel G. Toedter, Gary Shults, Justine Von Feldt, Joan Marie Leonard, Mary B. TI Vitamin D, Metabolic Dyslipidemia, and Metabolic Syndrome in Rheumatoid Arthritis SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Lipoproteins; Metabolic syndrome; Rheumatoid arthritis; Triglycerides; Vitamin D ID BETA-CELL DYSFUNCTION; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; D DEFICIENCY; 25-HYDROXYVITAMIN D; HYPOVITAMINOSIS-D; RISK; ASSOCIATION; CHOLESTEROL; PREVALENCE AB PURPOSE: Vitamin D deficiency is a potential risk factor for cardiometabolic disease. We investigated the associations between vitamin D and dyslipidemia and the metabolic syndrome in patients with rheumatoid arthritis, a group at high risk for cardiovascular disease. METHODS: Serum 25(OH) vitamin D and lipoprotein levels were measured at baseline in a random sample of 499 participants, ages 18-85 years, enrolled in a randomized trial of golimumab (GOlimumab Before Employing methotrexate as the First-line Option in the treatment of Rheumatoid arthritis of Early onset or GO-BEFORE Trial). Participants had rheumatoid arthritis with active disease, and were naive to methotrexate and biologic therapies. Multivariable linear regression was performed to assess associations between vitamin D levels and lipoprotein fractions. Multivariable logistic regression was performed to determine the odds of hyperlipidemia and the metabolic syndrome in participants with vitamin D deficiency (<20 ng/mL). RESULTS: In multivariable linear regression, vitamin D levels (per 10 ng/mL) were associated inversely with low-density lipoprotein (beta: -0.029 [-0.049, -0.0091], P = .004) and triglyceride (beta: -0.094 [-0.15, -0.039] P = .001) levels, adjusted for demographic, cardiovascular, and disease-specific variables. Vitamin D and high-density lipoprotein levels were not associated in univariate or multivariate analyses. Vitamin D deficiency was associated independently with an increased odds of hyperlipidemia (odds ratio 1.72; 95% confidence interval, 1.10-2.45; P = .014) and metabolic syndrome (odds ratio 3.45; 95% confidence interval, 1.75-6.80; P < .001) in adjusted models. CONCLUSIONS: In conclusion, vitamin D deficiency was associated with the metabolic syndrome and dyslipidemia in rheumatoid arthritis, suggesting a potential role in cardiovascular disease risk. Large-scale, prospective studies are needed to determine if vitamin D supplementation improves lipoprotein levels and reduces cardiovascular risk in rheumatoid arthritis. (C) 2012 Elsevier Inc. All rights reserved. The American Journal of Medicine (2012) 125, 1036.e9-1036.e15 C1 [Baker, Joshua F.] Univ Penn, Dept Med, Div Rheumatol, Philadelphia, PA 19104 USA. [Mehta, Nehal N.; Shults, Justine; Leonard, Mary B.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Mehta, Nehal N.] Univ Penn, Dept Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA. [Baker, Daniel G.] Centocor Res & Dev, Clin Immunol, Malvern, PA USA. [Toedter, Gary] Centocor Res & Dev, Biomarker, Malvern, PA USA. [Von Feldt, Joan Marie] Vet Affairs Med Ctr, Div Rheumatol, Philadelphia, PA USA. [Leonard, Mary B.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA. RP Baker, JF (reprint author), Hosp Univ Penn, Dept Med, Div Rheumatol, 8 Penn Tower Bldg,1 Convent Ctr Blvd, Philadelphia, PA 19104 USA. EM bakerjo@uphs.upenn.edu NR 36 TC 5 Z9 5 U1 1 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT PY 2012 VL 125 IS 10 AR 1036.e9 DI 10.1016/j.amjmed.2012.01.025 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 010UR UT WOS:000309120400036 PM 22800875 ER PT J AU Greenup, RA Camp, MS Taghian, AG Buckley, J Coopey, SB Gadd, M Hughes, K Specht, M Smith, BL AF Greenup, Rachel A. Camp, Melissa S. Taghian, Alphonse G. Buckley, Julliette Coopey, Suzanne B. Gadd, Michele Hughes, Kevin Specht, Michelle Smith, Barbara L. TI Cost Comparison of Radiation Treatment Options After Lumpectomy for Breast Cancer SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID CARCINOMA-IN-SITU; 20-YEAR FOLLOW-UP; CONSERVING SURGERY; RANDOMIZED TRIAL; IRRADIATION; RADIOTHERAPY; MASTECTOMY; THERAPY; EXCISION; IMPACT AB Radiation therapy (RT) after lumpectomy for breast cancer can be delivered with several different regimens. We evaluated a cost-minimization strategy to select among RT options. An institutional review board (IRB)-approved retrospective review identified a sample of 100 women who underwent lumpectomy for invasive or in situ breast cancer during 2009. Post lumpectomy RT options included: no radiation in women a parts per thousand yen70 years [T1N0, estrogen receptor (ER)+] per Cancer and Leukemia Group B (CALGB) 9343 (no-RT), accelerated external-beam partial-breast irradiation (APBI), and Canadian fractionation (C-RT), as alternatives to standard whole-breast radiation therapy (WBRT). Eligibility for RT regimens was based on published criteria. RT costs were estimated using the 2011 US Medicare Physician Fee Schedule and average Current Procedural Terminology (CPT) codes billed per regimen at our institution. Costs were modeled in a 1,000-patient theoretical cohort. Median patient age was 56.5 years (range 32-93 years). Tumor histology included invasive ductal cancer (78 %), ductal carcinoma in situ (DCIS) (15 %), invasive lobular cancer (6 %), and mixed histology (1 %). Median tumor size was 1 cm (range 0.2-5 cm). Estimated per-patient cost of radiation was US$5,341.81 for APBI, US$9,121.98 for C-RT, and US$13,358.37 for WBRT. When patients received the least expensive radiation regimen for which they were eligible, 14 % received no-RT, 44 % received APBI, 7 % received C-RT, and 35 % defaulted to WBRT. Using a cost-minimization strategy, estimated RT costs were US$7.67 million, versus US$13.36 million had all patients received WBRT, representing cost savings of US$5.69 million per 1,000 patients treated. A cost-minimization strategy results in a 43 % reduction in estimated radiation costs among women undergoing breast conservation. C1 [Greenup, Rachel A.; Camp, Melissa S.; Taghian, Alphonse G.; Buckley, Julliette; Coopey, Suzanne B.; Gadd, Michele; Hughes, Kevin; Specht, Michelle; Smith, Barbara L.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. RP Greenup, RA (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. EM Blsmith1@partners.org OI Hughes, Kevin/0000-0003-4084-6484 NR 26 TC 20 Z9 21 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD OCT PY 2012 VL 19 IS 10 BP 3275 EP 3281 DI 10.1245/s10434-012-2546-5 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA 003VG UT WOS:000308638900025 PM 22851048 ER PT J AU Mueller, M Celik, S Biener, M Vafaie, M Schwoebel, K Wollert, KC Januzzi, JL Katus, HA Giannitsis, E AF Mueller, M. Celik, S. Biener, M. Vafaie, M. Schwoebel, K. Wollert, K. C. Januzzi, J. L. Katus, H. A. Giannitsis, E. TI Diagnostic and prognostic performance of a novel high-sensitivity cardiac troponin T assay compared to a contemporary sensitive cardiac troponin I assay in patients with acute coronary syndrome SO CLINICAL RESEARCH IN CARDIOLOGY LA English DT Article DE High-sensitivity troponin; Acute coronary syndrome; Prognosis; Early diagnosis ID ELEVATION MYOCARDIAL-INFARCTION; EARLY INVASIVE STRATEGY; CLINICAL-PERFORMANCE; 99TH PERCENTILE; ARTERY DISEASE; RISK; OUTCOMES; TRIAL AB The study sought to compare the clinical performance of two more sensitive cardiac troponin (cTn) assays, a novel high-sensitivity (hs) troponin T assay and a contemporary cTnI assay. We measured hs-cTnT (Roche TnThs) and cTnI (Siemens Centaur Ultra) on presentation in 1,384 patients with suspected acute coronary syndrome (ACS) who underwent early invasive strategy within 24 h after presentation. Kaplan-Meier, Cox proportional hazards, and receiver-operating characteristic (ROC) analysis was used to compare their prognostic performance for the prediction of all-cause death and death/MI (myocardial infarction) after a median of 271 days. We also compared the diagnostic performance of these assays on presentation for early diagnosis of non-STEMI. Both hs-cTnT and cTnI were independently predictive of long-term death (OR 3.51 vs. 2.19) and the composite of death/MI (OR 9.24 vs. 3.61), across the spectrum of ACS and in patients without ACS. When used as a continuous variable, ROC analysis demonstrated significantly higher areas under the curve (AUC) for hs-cTnT as compared to cTnI for the prediction of death/MI (0.721 vs. 0.672, P = 0.024), a trend to better prediction of all-cause death (0.721 vs. 0.672, P = 0.093) and significantly higher AUC for early diagnosis of non-STEMI (0.965 vs. 0.901, P < 0.001). Using the 99th percentile cutoff for hs-cTnT and cTnI, both assays enable prediction of adverse long-term outcomes and earlier diagnosis of non-STEMI. Used as a continuous variable, the hs-cTnT assay showed superior performance compared to the cTnI assay, especially in regard to prognosis. C1 [Mueller, M.; Celik, S.; Biener, M.; Vafaie, M.; Schwoebel, K.; Katus, H. A.; Giannitsis, E.] Univ Klinikum Heidelberg, Med Klin, Abt Innere Med 3, D-69120 Heidelberg, Germany. [Wollert, K. C.] Hannover Med Sch, Klin Kardiol & Angiol, D-30623 Hannover, Germany. [Januzzi, J. L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Giannitsis, E (reprint author), Univ Klinikum Heidelberg, Med Klin, Abt Innere Med 3, Neuenheimer Feld 410, D-69120 Heidelberg, Germany. EM evangelos.giannitsis@med.uni-heidelberg.de RI Katus, Hugo/P-1712-2016 FU Roche Diagnostics, Germany; Roche Diagnostics FX EG has received financial support for clinical trials from Roche Diagnostics, Germany. He is consultant to Roche Diagnostics and receives honoraria for lectures from Roche Diagnostics. JLJ has received grant support from Roche Diagnostics, and has received honoraria for lectures from Roche Diagnostics. HAK has developed the cTnT assay and holds a patent jointly with Roche Diagnostics. He has received grants and research support from several companies, and has received honoraria for lectures from Roche Diagnostics. NR 23 TC 31 Z9 31 U1 0 U2 5 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1861-0684 J9 CLIN RES CARDIOL JI Clin. Res. Cardiol. PD OCT PY 2012 VL 101 IS 10 BP 837 EP 845 DI 10.1007/s00392-012-0469-6 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 008OS UT WOS:000308967000007 PM 22627889 ER PT J AU Levkovitz, Y Alpert, JE Brintz, CE Mischoulon, D Papakostas, GI AF Levkovitz, Y. Alpert, J. E. Brintz, C. E. Mischoulon, D. Papakostas, G. I. TI Effects of S-adenosylmethionine augmentation of serotonin-reuptake inhibitor antidepressants on cognitive symptoms of major depressive disorder SO EUROPEAN PSYCHIATRY LA English DT Article DE Pharmacotherapy; Major depression; S-adenosylmethionine; Cognitive function; One-carbon cycle ID ADENOSYL-L-METHIONINE; ALZHEIMERS-DISEASE; MUSCARINIC RECEPTORS; RISK-FACTORS; NICOTINAMIDE; DEFICITS; RATS AB Major depressive disorder (MDD) is often accompanied by significant cognitive impairment, and there are limited interventions specific to this particular symptom. S-adenosylmethionine (SAMe), a naturally occurring molecule which serves as a major methyl-donor in human cellular metabolism, is required for the synthesis and maintenance of several neurotransmitters that have been implicated in the pathophysiology and treatment of cognitive dysfunction in MDD. Objectives: This study is a secondary analysis of a clinical trial involving the use of adjunctive SAMe for MDD. Methods: Forty-six serotonin-reuptake inhibitor (SRI) non-responders with MDD enrolled in a 6-week, double-blind, randomized trial of adjunctive oral SAMe were administered the self-rated cognitive and physical symptoms questionnaire (CPFQ), a validated measure of cognitive as well as physical symptoms of MDD, before and after treatment. Results: There was a greater improvement in the ability to recall information (P = 0.04) and a trend towards statistical significance for greater improvement in word-finding (P = 0.09) for patients who received adjunctive SAMe than placebo. None of the remaining five items reached statistical significance. Conclusions: These preliminary data suggest that SAMe can improve memory-related cognitive symptoms in depressed patients, and warrant replication. (C) 2011 Elsevier Masson SAS. All rights reserved. C1 [Levkovitz, Y.] Tel Aviv Univ, Shalvata Mental Hlth Ctr, Dept Psychiat, IL-69978 Tel Aviv, Israel. [Levkovitz, Y.; Alpert, J. E.; Brintz, C. E.; Mischoulon, D.; Papakostas, G. I.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Levkovitz, Y (reprint author), Tel Aviv Univ, Shalvata Mental Hlth Ctr, Dept Psychiat, Hamargoa 4,POB 94, IL-69978 Tel Aviv, Israel. EM levkovit@netvision.net.il RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X FU Abbott Laboratories; Alkermes; Lichtwer Pharma GmbH; Lorex Pharmaceuticals; Aspect Medical Systems; Astra-Zeneca; Bristol-Myers Squibb Company; Cephalon; Cyberonics; Eli Lilly Company; Forest Pharmaceuticals Inc.; GlaxoSmithkline; J & J Pharmaceuticals; Novartis; Organon Inc.; PamLab; LLC; Pfizer Inc.; Pharmavite; Roche; Sanofi/Synthelabo; Solvay Pharmaceuticals, Inc.; Wyeth-Ayerst Laboratories; Laxdale (Amarin); Nordic Naturals; Ganeden; SwissMedica; MGH Psychiatry Academy through Independent Medical Education (IME); Forest Pharmaceuticals; National Institute of Mental Health; PAMLAB LLC; Precision Human Biolaboratories FX J.E.A. has received research support from: Abbott Laboratories, Alkermes, Lichtwer Pharma GmbH, Lorex Pharmaceuticals; Aspect Medical Systems, Astra-Zeneca, Bristol-Myers Squibb Company, Cephalon, Cyberonics, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithkline, J & J Pharmaceuticals, Novartis, Organon Inc., PamLab, LLC, Pfizer Inc., Pharmavite, Roche, Sanofi/Synthelabo, Solvay Pharmaceuticals, Inc., and Wyeth-Ayerst Laboratories. He has participated on advisory boards for or consulted to: Eli Lilly & Company, Pamlab LLC, and Pharmavite LLC. He has received speakers' honoraria from: Eli Lilly & Company, Janssen, Organon, Reed Medical Education. He has no relevant equity holdings, patents or royalties.; D. M. has received support from the following companies during the past 3 years. He has research support (usually as donated medications for clinical trials) from Laxdale (Amarin), Nordic Naturals, Ganeden, SwissMedica. He has participated on advisory boards for or consulted to Bristol-Meyers Squibb Company, PamLab. He has received speakers' honoraria from Pamlab, Virbac; Nordic Naturals. He has received support from Pamlab for writing. He has no relevant equity holdings. He has patents/royalties from Back Bay Scientific for PMS Escape (patent application pending). He receives receive honoraria from Reed Medical Education (a company working as a logistics collaborator for the MGH Psychiatry Academy). The education programs conducted by the MGH Psychiatry Academy were supported through Independent Medical Education (IME) grants from pharmaceutical companies co-supporting programs along with participant tuition. Commercial entities currently supporting the MGH Psychiatry Academy are listed on the Academy's website http://www.mghcme.org. No payment from any individual entity or company has exceeded $10,000 per year.; Dr Papakostas has received research support from Bristol-Myers Squibb Company, Forest Pharmaceuticals, the National Institute of Mental Health, PAMLAB LLC, Pfizer Inc., and Ridge Diagnostics (formerly known as Precision Human Biolaboratories). NR 31 TC 4 Z9 4 U1 0 U2 5 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PD OCT PY 2012 VL 27 IS 7 BP 518 EP 521 DI 10.1016/j.eurpsy.2011.03.006 PG 4 WC Psychiatry SC Psychiatry GA 010OX UT WOS:000309105000008 PM 21665441 ER PT J AU Lee, LJ Viswanathan, AN AF Lee, Larissa J. Viswanathan, Akila N. TI Combined chemotherapy and radiation improves survival for node-positive endometrial cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE FIGO IIIC endometrial cancer; Node-positive endometrial cancer; Radiation therapy; Endometrioid histology ID GYNECOLOGIC-ONCOLOGY-GROUP; ADJUVANT CHEMOTHERAPY; FAILURE PATTERNS; STAGE-I; CARCINOMA; THERAPY; TRIAL; RISK; RADIOTHERAPY; METASTASIS AB Objective. To evaluate the clinical outcomes for women with node-positive endometrioid adenocarcinoma of the uterus Methods. Records were reviewed for 66 patients with Stage IIIC endometrioid adenocarcinoma diagnosed between 1/1995 and 12/2009. Study inclusion required TAH, BSO and negative chest imaging. Papillary serous and clear cell histologies were excluded. Adjuvant treatment was external beam radiation (RT) alone in 18 patients (27%), combined chemotherapy and RT in 44 (67%), chemotherapy alone in 1 (2%), and no adjuvant therapy in 3 (5%). The median follow-up was 48 months. Results. Of 66 patients, 56 (85%) had positive pelvic nodes only, 5 (8%) had positive para-aortic nodes only, and 5 (8%) had both. Of the 62 patients who received adjuvant RT, only 4 (6%) had an in-field recurrence, including 2 with residual disease after surgery. Disease-free (DFS) and overall (OS) survival rates at 5 years were 71% and 81%, respectively. By adjuvant treatment modality, 5-year DFS and OS rates were 63% and 67% for RT alone and 79% and 90% for combined modality therapy (p=0.15 and p<0.01). On multivariate analysis, combined modality therapy significantly improved DFS (HR 0.12, 95% CI 0.03-0.49, p<0.01) and OS (HR 0.20, 95% CI 0.05-0.75, p=0.02) compared to adjuvant RT alone. Conclusions. Compared to RT alone, combined modality therapy decreased recurrence and improved survival in patients with node-positive endometrioid adenocarcinoma of the uterus. In addition, external beam RT resulted in excellent local and regional control. Future studies are needed to define the optimal chemotherapy regimen, sequencing, and radiation fields. (C) 2012 Elsevier Inc. All rights reserved. C1 [Lee, Larissa J.; Viswanathan, Akila N.] Harvard Univ, Dept Radiat Oncol, Dana Farber Canc Inst, Brigham & Womens Hosp,Med Sch, Boston, MA 02115 USA. RP Viswanathan, AN (reprint author), Harvard Univ, Dept Radiat Oncol, Dana Farber Canc Inst, Brigham & Womens Hosp,Med Sch, 75 Francis St L2, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu FU NCI NIH HHS [K07 CA117979] NR 22 TC 16 Z9 16 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD OCT PY 2012 VL 127 IS 1 BP 32 EP 37 DI 10.1016/j.ygyno.2012.06.026 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 005XQ UT WOS:000308783800007 PM 22735786 ER PT J AU Esselen, KM Rodriguez, N Growdon, W Krasner, C Horowitz, NS Campos, S AF Esselen, Katharine M. Rodriguez, Noah Growdon, Whitfield Krasner, Carolyn Horowitz, Neil S. Campos, Susana TI Patterns of recurrence in advanced epithelial ovarian, fallopian tube and peritoneal cancers treated with intraperitoneal chemotherapy SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ovarian; Fallopian tube; Peritoneal; Recurrence; Intraperitoneal chemotherapy ID SECONDARY CYTOREDUCTIVE SURGERY; CARCINOMA; CISPLATIN; PACLITAXEL AB Objectives. To examine the distribution and outcomes of recurrent disease in patients with ovarian, fallopian tube and peritoneal cancers after optimal cytoreduction and adjuvant intraperitoneal (IP) chemotherapy. Methods. All patients diagnosed with ovarian, fallopian tube, or peritoneal cancer between 2004 and 2009 who underwent optimal cytoreductive surgery and received adjuvant intravenous (IV) and IP chemotherapy with paclitaxel and a platinum-based agent were eligible. Age, performance status, tumor origin, stage, and grade were recorded. First recurrences were identified using CA125 values, radiographic studies, operative notes, and pathology reports. Sites of recurrence were classified as intraperitoneal (IP), extraperitoneal (EP) or distant. Kaplan-Meier estimates and Cox multivariate regression models were used to assess the associations between recurrent disease distribution and progression-free survival (PFS) and overall survival (OS). Results. One hundred forty-three patients met the criteria for inclusion. The majority were Stage III (86%) and serous histology (77%). Eighty-four (58.7%) received IV/IP paclitaxel/cisplatin per GOG-172 and 59 (41.3%) received IV/IP paclitaxel/carboplatin. Seventy-two percent completed 6 cycles. Ninety (62.9%) patients manifested a recurrence. One-hundred twelve sites of recurrence were identified with 70 (62.5%) IP and 42 (37.5%) EP and distant sites. Nineteen (21%) recurred in more than one site, i.e. both IP and EP locations. Site of recurrence did not impact OS, however, patients who recurred in multiples sites had significantly worse OS (p<0.001). Conclusion. Approximately 40% of patients treated with IP chemotherapy have a first recurrence outside the peritoneal cavity. Though site of recurrence did not affect OS those with multi-focal recurrence demonstrate worse survival. (C) 2012 Elsevier Inc. All rights reserved. C1 [Horowitz, Neil S.; Campos, Susana] Dana Farber Canc Inst, Boston, MA 02215 USA. [Esselen, Katharine M.; Rodriguez, Noah; Horowitz, Neil S.] Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02115 USA. [Esselen, Katharine M.; Growdon, Whitfield] Massachusetts Gen Hosp, Div Gynecol Oncol, Dept Obstet & Gynecol, Boston, MA 02114 USA. [Krasner, Carolyn] Massachusetts Gen Hosp, Dept Med, Div Gynecol Oncol, Boston, MA 02114 USA. [Campos, Susana] Brigham & Womens Hosp, Dept Med, Div Gynecol Oncol, Boston, MA 02115 USA. RP Campos, S (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM kesselen@partners.org; NORodriguez@llu.edu; wgrowdon@partners.org; cnkrasner@partners.org; nhorowitz@partners.org; Susana_campos@dfci.harvard.edu NR 9 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD OCT PY 2012 VL 127 IS 1 BP 51 EP 54 DI 10.1016/j.ygyno.2012.05.026 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 005XQ UT WOS:000308783800011 PM 22659193 ER PT J AU Matulonis, UA Sharma, S Ghamande, S Gordon, MS Del Prete, SA Ray-Coquard, I Kutarska, E Liu, H Fingert, H Zhou, XF Danaee, H Schilder, RJ AF Matulonis, Ursula A. Sharma, Sudarshan Ghamande, Sharad Gordon, Michael S. Del Prete, Salvatore A. Ray-Coquard, Isabelle Kutarska, Elzbieta Liu, Hua Fingert, Howard Zhou, Xiaofei Danaee, Hadi Schilder, Russell J. TI Phase II study of MLN8237 (alisertib), an investigational Aurora A kinase inhibitor, in patients with platinum-resistant or -refractory epithelial ovarian, fallopian tube, or primary peritoneal carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Aurora A kinase; Ovarian cancer; MLN8237; Platinum-refractory; Platinum-resistant ID PEGYLATED LIPOSOMAL DOXORUBICIN; CANCER PATIENTS; A KINASE; TRIAL; OVEREXPRESSION; CELL; TUMORS AB Objectives. Aurora A kinase (AAK), a key mitotic regulator, is implicated in the pathogenesis of several tumors, including ovarian cancer. This single-arm phase II study assessed single-agent efficacy and safety of the investigational AAK inhibitor MLN8237 (alisertib), in patients with platinum-refractory or -resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. Methods. Adult women with malignant, platinum-treated disease received MLN8237 50 mg orally twice daily for 7 days plus 14 days' rest (21-day cycles). The primary endpoint was combined objective tumor response rate per Response Evaluation Criteria in Solid Tumors (RECIST) and/or CA-125 criteria. Secondary endpoints included response duration, clinical benefit rate, progression-free survival (PFS), time-to-progression (TTP), and safety. Results. Thirty-one patients with epithelial ovarian (n=25), primary peritoneal (n=5), and fallopian tube carcinomas (n=1) were enrolled. Responses of 6.9-11.1 month duration were observed in 3 (10%) patients with platinum-resistant ovarian cancer. Sixteen (52%) patients achieved stable disease with a mean duration of response of 2.86 months and which was durable for >= 3 months in 6 (19%). Median PFS and TTP were 1.9 months. Most common drug-related grade >= 3 adverse events were neutropenia (42%), leukopenia (23%), stomatitis, and thrombocytopenia (each 19%); 6% reported febrile neutropenia. Conclusions. These data suggest that MLN8237 has modest single-agent antitumor activity and may produce responses and durable disease control in some patients with platinum-resistant ovarian cancer. MLN8237 is currently undergoing evaluation in a phase I/II trial with paclitaxel in recurrent ovarian cancer. (C) 2012 Published by Elsevier Inc. C1 [Matulonis, Ursula A.] Yawkey Ctr Canc Care, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. [Sharma, Sudarshan] Hinsdale Hosp, Hinsdale, IL USA. [Ghamande, Sharad] Med Coll Georgia, Augusta, GA 30912 USA. [Gordon, Michael S.] Pinnacle Oncol Hematol, Scottsdale, AZ USA. [Del Prete, Salvatore A.] Bennett Canc Ctr, Stamford, CT USA. [Ray-Coquard, Isabelle] Ctr Leon Berard, F-69373 Lyon, France. [Ray-Coquard, Isabelle] EAM 4129 Sante Individu Soc, Lyon, France. [Kutarska, Elzbieta] Lublin Oncol Ctr, Lublin, Poland. [Liu, Hua; Fingert, Howard; Zhou, Xiaofei; Danaee, Hadi] Millennium Pharmaceut Inc, Cambridge, MA USA. [Schilder, Russell J.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Matulonis, UA (reprint author), Yawkey Ctr Canc Care, Dept Med Oncol, Dana Farber Canc Inst, 450 Brookline Ave,14th Floor, Boston, MA 02215 USA. EM Ursula_Matulonis@dfci.harvard.edu FU Millennium Pharmaceuticals, Inc. FX Research support: Millennium Pharmaceuticals, Inc. NR 30 TC 53 Z9 53 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD OCT PY 2012 VL 127 IS 1 BP 63 EP 69 DI 10.1016/j.ygyno.2012.06.040 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 005XQ UT WOS:000308783800013 PM 22772063 ER PT J AU Horowitz, NS Olawaiye, AB Borger, DR Growdon, WB Krasner, CN Matulonis, UA Liu, JF Lee, J Brard, L Dizon, DS AF Horowitz, N. S. Olawaiye, A. B. Borger, D. R. Growdon, W. B. Krasner, C. N. Matulonis, U. A. Liu, J. F. Lee, J. Brard, L. Dizon, D. S. TI Phase II trial of erlotinib in women with squamous cell carcinoma of the vulva SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Vulvar carcinoma; Chemotherapy; Erlotinib ID GROWTH-FACTOR RECEPTOR; GENE COPY NUMBER; GYNECOLOGIC-ONCOLOGY-GROUP; LUNG-CANCER PATIENTS; CLINICAL-RESPONSE; TYROSINE KINASE; EGFR; RECURRENT; EXPRESSION; CISPLATIN AB Objective. To evaluate the efficacy and toxicity of erlotinib in the management of sguamous cell carcinoma (SCC) of the vulva. Methods. Patients with vulvar lesions amenable to surgery or chemoradiation (cohort 1) or those with metastatic measurable disease (cohort 2) received erlotinib 150 mg daily. Patients were monitored for toxicity. Responses were determined by digital photography or RECIST 1.1. Cohort 1 underwent pre and post treatment biopsies. EGFR immunohistochemistry (IHC), fluorescence in-situ hybridization (FISH), and mutational analysis were performed. Results. 41 patients were enrolled: 17 in cohort 1 and 24 in cohort 2. Notable grade 3 or 4 toxicities included allergic reaction (1), diarrhea/electrolyte abnormalities (3), ischemic colitis (1), and renal failure (3) and electrolyte abnormalities (n = 2). Mean number of cycles for cohort 2 was 3.3. Overall clinical benefit rate was 67.5% with 11 (27.5%) partial responses (PR), 16 (40.0%) stable disease (SD), and 7 (17.5%) progressive disease. Responses were of short duration. All pre and post treatment biopsies exhibited 2-3 + EGFR staining. 5 of 14 patients (35%) were found to have EGFR amplification (n = 3) or high polysomy/trisomy (n = 2). These five patients had either a PR (n = 3) or SD (n = 2). Gain of function mutations were not been identified. Conclusions. This is the first reported controlled trial evaluating erlotinib for the management of vulvar carcinoma. Toxicities were acceptable given the lack of treatment options for these patients. Given the observed clinical benefits erlotinib may represent one of the most active agents available to treat vulvar SCC. (C) 2012 Elsevier Inc. All rights reserved. C1 [Horowitz, N. S.; Matulonis, U. A.; Liu, J. F.; Lee, J.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Olawaiye, A. B.; Borger, D. R.; Growdon, W. B.; Krasner, C. N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Brard, L.; Dizon, D. S.] Brown Univ, Sch Med, Women & Infants Hosp Rhode Isl, Providence, RI 02912 USA. RP Horowitz, NS (reprint author), Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. EM nhorowitz@partners.org OI Brard, Laurent/0000-0003-0065-1826 NR 38 TC 21 Z9 21 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD OCT PY 2012 VL 127 IS 1 BP 141 EP 146 DI 10.1016/j.ygyno.2012.06.028 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 005XQ UT WOS:000308783800027 PM 22750258 ER PT J AU Krasner, CN Poveda, A Herzog, TJ Vermorken, JB Kaye, SB Nieto, A Claret, PL Park, YC Parekh, T Monk, BJ AF Krasner, Carolyn N. Poveda, Andres Herzog, Thomas J. Vermorken, Jan B. Kaye, Stanley B. Nieto, Antonio Lardelli Claret, Pilar Park, Youn Choi Parekh, Trilok Monk, Bradley J. TI Patient-reported outcomes in relapsed ovarian cancer: Results from a randomized Phase III study of trabectedin with pegylated liposomal doxorubicin (PLD) versus PLD Alone SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Trabectedin; Yondelis (R); Pegylated liposomal doxorubicin; DOXIL (R); Relapsed ovarian cancer; Patient-reported outcome ID QUALITY-OF-LIFE; GYNECOLOGIC-ONCOLOGY-GROUP; CLINICAL-TRIALS; QUESTIONNAIRE MODULE; 1ST-LINE TREATMENT; STAGE-III; PACLITAXEL; CISPLATIN; CHEMOTHERAPY; CYCLOPHOSPHAMIDE AB Objective. Trabectedin in combination with PLD improves progression-free suivival (PFS) and overall response rate (ORR) in comparison to PLD alone in patients with relapsed ovarian cancer (J Clin Oncol; 2010 28:3107-14). Here we report the impact of the treatment combination on patient-reported functional status and symptoms. Methods. Patient-reported outcome (PRO) questionnaires, EORTC-QLQ C30, OV28, and EQ-5D were completed by patients at screening and on Day 1 of every other treatment cycle starting with Cycle 1, and at the end-of-treatment visit. Results. Of the 672 patients randomized in this study, 663 treated patients completed at least one of the baseline questionnaires. Median cycles of treatment was 6 (131 days) for the combination arm and 5 (143 days) for the monotherapy arm. Longitudinal data analyses showed no significant differences between the treatment arms for any of the pre-specified scales. Similar analyses of other scales, including Health Index scores and Health State on the Visual Analog Scale, support these findings. Start of subsequent therapy was significantly delayed in the combination arm compared with the monotherapy arm (p = 0.0032). Conclusions. The addition of trabectedin to PLD led to little or no decrement in patient-reported functional status and symptoms in patients with relapsed ovarian cancer, as compared to treatment with PLD alone. The combination led to manageable and non-cumulative overall toxicity with a fewer PLD-associated adverse events, and a significant improvement in PFS and ORR compared to single agent. (C) 2012 Elsevier Inc. All rights reserved. C1 [Krasner, Carolyn N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Poveda, Andres] Fdn Inst Valenciano Oncol, Valencia, Spain. [Herzog, Thomas J.] Columbia Univ, Med Ctr, New York, NY USA. [Vermorken, Jan B.] Univ Ziekenhuis Antwerpen, Edegem, Belgium. [Kaye, Stanley B.] Royal Marsden Hosp, Sutton, Surrey, England. [Nieto, Antonio; Lardelli Claret, Pilar] SA, PharmaMar, Madrid, Spain. [Park, Youn Choi; Parekh, Trilok] Janssen Res & Dev LLC, Raritan, NJ USA. [Monk, Bradley J.] Creighton Univ, Sch Med, St Josephs Hosp & Med Ctr, Phoenix, AZ USA. RP Krasner, CN (reprint author), Massachusetts Gen Hosp, 100 Blossom St Cox 5, Boston, MA 02114 USA. EM cnkrasner@partners.org FU Janssen Research & Development, L.L.C.; PharmaMar, S.A.; Janssen Research Development FX Supported by Janssen Research & Development, L.L.C. and PharmaMar, S.A.; Dr Krasner and Dr Poveda declare that there are no conflicts of interest Dr Herzog has been a consultant for Roche, Merck, Nektar, Morphotek, and J&J. Dr. Vermorken received honoraria from Pharmamar. Dr. Kaye serves as a clinical advisory board member for Janssen R&D. Drs Nieto and Lardelli Claret are employees of Pharmamar and have stock ownership in Zeltia. Drs. Parekh and Park are employees of Janssen Research & Development and have stock ownership in Johnson & Johnson. Dr. Monk received honoraria and research funding from Janssen Research & Development. NR 29 TC 13 Z9 13 U1 0 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD OCT PY 2012 VL 127 IS 1 BP 161 EP 167 DI 10.1016/j.ygyno.2012.06.034 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 005XQ UT WOS:000308783800030 PM 22765965 ER PT J AU Oh, JS Jang, JH Jung, WH Kang, DH Choi, JS Choi, CH Kubicki, M Shenton, ME Kwon, JS AF Oh, Jungsu S. Jang, Joon Hwan Jung, Wi Hoon Kang, Do-Hyung Choi, Jung-Seok Choi, Chi-Hoon Kubicki, Marek Shenton, Martha E. Kwon, Jun Soo TI Reduced fronto-callosal fiber integrity in unmedicated OCD patients: A diffusion tractography study SO HUMAN BRAIN MAPPING LA English DT Article DE obsessive-compulsive disorder; corpus callosum; diffusion tractography; orbitofrontal; dorsolateral prefrontal; fiber integrity ID OBSESSIVE-COMPULSIVE DISORDER; HUMAN CORPUS-CALLOSUM; WHITE-MATTER ABNORMALITIES; TENSOR TRACTOGRAPHY; SEX-DIFFERENCES; HUMAN BRAIN; SCHIZOPHRENIA; CONNECTIVITY; CORTEX; SCALE AB It is widely accepted that abnormalities in the frontal area of the brain underpin the pathophysiology of obsessive-compulsive disorder (OCD). Fundamental to this investigation is the delineation of frontal white matter tracts including dorsal and ventral frontal projections of interhemispheric connections. While previous investigations of OCD have examined the dorsal and ventral frontal regions, the corresponding callosal connections have not been investigated, despite their importance. We recruited twenty patients with OCD (15 drug-naive and 5 currently unmedicated) and demographically similar healthy controls, and conducted fiber tractography and post hoc quantitative analysis using diffusion tensor imaging. We extracted fractional anisotropy (FA) of the fronto-callosal fibers along the entire length of the tract. Function-specific [by the Brodmann area region-of-interest (ROI) approach] and region-specific (by the length-parameterization approach) tracts were defined. In addition, we devised a new index of dorsal-ventral imbalance (DVII) of fiber integrity. Significant FA decreases were observed in orbitofrontal and dorsolateral prefrontal projections of the corpus callosum (P < 0.05, false discovery rate-corrected) with higher function/region sensitivity than voxel-based or ROI-based approaches. Importantly, OCD patients also exhibited significantly higher ventral-greater-than-dorsal asymmetry of FA values than normal controls (P < 0.05, FDR-corrected). This study is the first to investigate fiber integrity in the dorsal/ventral frontal parts of the callosal tractography in unmedicated OCD patients. Using a more quantitative method in terms of functional and regional specificity than previous studies, we report abnormalities in interhemispheric connectivity of both dorsal and ventral networks in the pathophysiology of OCD. Hum Brain Mapp 33:24412452, 2012. (c) 2011 Wiley Periodicals, Inc. C1 [Oh, Jungsu S.; Jang, Joon Hwan; Jung, Wi Hoon; Kang, Do-Hyung; Choi, Jung-Seok; Kwon, Jun Soo] Seoul Natl Univ, Dept Psychiat, Coll Med, Seoul 110744, South Korea. [Oh, Jungsu S.] Asan Med Ctr, Dept Nucl Med, Seoul, South Korea. [Choi, Chi-Hoon] Natl Med Ctr, Dept Radiol, Seoul, South Korea. [Kubicki, Marek; Shenton, Martha E.] Harvard Univ, Clin Neurosci Div, Lab Neurosci, Dept Psychiat,VA Boston Healthcare Syst, Brockton, MA 02401 USA. [Kubicki, Marek; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Psychiat Neuroimaging Lab, Sch Med, Boston, MA 02115 USA. [Kwon, Jun Soo] Seoul Natl Univ, Brain & Cognit Sci WCU Program, Coll Nat Sci, Seoul 110744, South Korea. RP Kwon, JS (reprint author), Seoul Natl Univ, Dept Psychiat, Coll Med, 101 Daehak No, Seoul 110744, South Korea. EM kwonjs@snu.ac.kr RI Kwon, Jun Soo/J-2734-2012; Kang, Do-Hyung/J-5358-2012; OI JUNG, WI HOON/0000-0002-8697-9584; Oh, Jungsu/0000-0002-1925-8103 FU Brain & Cognitive Science (World Class University program) through the Korea Science and Engineering Foundation [R32-10142]; Ministry of Education, Science, and Technology FX Contract grant sponsors: Brain & Cognitive Science (World Class University program-R32-10142) through the Korea Science and Engineering Foundation funded by the Ministry of Education, Science, and Technology. NR 66 TC 11 Z9 11 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD OCT PY 2012 VL 33 IS 10 BP 2441 EP 2452 DI 10.1002/hbm.21372 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 003DW UT WOS:000308589400015 PM 21922600 ER PT J AU Rosen, D Kathy-Hoffstadter-Thal Bao, R Tomaino, J Ceballos, C Russell, GJM Benkov, KJ AF Rosen, Danya Kathy-Hoffstadter-Thal Bao, Ruijin Tomaino, Juli Ceballos, Clare Russell, Gary J. M. Benkov, Keith J. TI Analysis of current treatments used in clinical practice in a pediatric summer camp population for children with inflammatory bowel disease SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE pediatrics; Crohn's disease; general clinical; ulcerative colitis; general clinical ID QUALITY-OF-LIFE; CROHNS-DISEASE; ULCERATIVE-COLITIS; THERAPY; AZATHIOPRINE; PREVALENCE; MANAGEMENT; INFLIXIMAB AB Background: Many treatment options exist for children with inflammatory bowel disease (IBD), yet the lack of clinical guidelines for management has lead to great variation in care. The purpose of this project was to evaluate current treatment modalities in children from the Northeast US who applied to the 2010 session of Camp Oasis, a Crohn's and Colitis Foundation of America (CCFA)-sponsored camp for children ages 817 with medically stable IBD. Methods: Patient demographics, medical history, and current medications were entered into the camp database. The subjects were divided into two groups; Crohn's disease (CD) or ulcerative colitis/indeterminate colitis (UC/IC). In all, 164 applicants were included, 121 (74%) with CD and 43 (26%) with UC/IC. Results: There were no significant differences between the two groups with respect to median age at the time of camp, median age at diagnosis, or median length of illness. Of the 121 applicants with CD, 13 (10.7%) were on an antibiotic, 56 (46.3%) were on a 5-aminosalicylate (5-ASA), 10 (8.3%) were on corticosteroids, 57 (47.1%) were on immunomodulators, and 44 (36.4%) were on a biologic agent. Six (5%) were on both an immunomodulator and a biologic agent. Of the 43 subjects with UC/IC, 27 (62.7%) were on a 5-ASA, two (4.7%) were on corticosteroids, 13 (30.2%) were on an immunomodulator, and four (9.3%) were on a biologic agent. The groups were similar with regard to surgery (20.7% for CD and 18.6% for UC/IC). Conclusions: Identifying current treatment patterns may serve to highlight variations in care among this pediatric IBD population. (Inflamm Bowel Dis 2012) C1 [Rosen, Danya; Kathy-Hoffstadter-Thal; Bao, Ruijin; Tomaino, Juli; Ceballos, Clare; Benkov, Keith J.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Russell, Gary J. M.] Mass Gen Hosp, Boston, MA USA. RP Benkov, KJ (reprint author), Mt Sinai Med Ctr, 1 Gustave L Levy Pl,Box 1656, New York, NY 10029 USA. EM keith.benkov@mssm.edu NR 20 TC 3 Z9 4 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD OCT PY 2012 VL 18 IS 10 BP 1818 EP 1824 DI 10.1002/ibd.22837 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 004YE UT WOS:000308716600003 PM 22069120 ER PT J AU Gregor, K Borrelli, B AF Gregor, Kristin Borrelli, Belinda TI Barriers to quitting smoking among medically ill smokers SO JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE Smoking cessation; Barriers to cessation; Medically ill smokers; Depressed mood; Motivation to quit smoking ID FAGERSTROM TOLERANCE QUESTIONNAIRE; NICOTINE DEPENDENCE; TRANSTHEORETICAL MODEL; CESSATION PROGRAM; CIGARETTE-SMOKING; PERCEIVED STRESS; MAJOR DEPRESSION; SELF-QUITTERS; YOUNG-ADULT; PREDICTORS AB Few studies examine predictors of smoking cessation among medically ill smokers, despite their high smoking prevalence. We prospectively examined barriers to smoking cessation in medically ill smokers, with age as a hypothesized moderator. Participants were smokers (N = 237, M (age) = 56.1, 53.6% females) receiving home-based nursing care. Baseline self-report questionnaires assessed barriers to cessation (demographics, smoking history, psychosocial, and medical factors). Smoking status was biochemically verified at 2- and 6-months post-intervention. Compared with younger smokers, older smokers had significantly lower levels of nicotine dependence, stress, and depressed mood and a greater prevalence of smoking-related diseases. Older smokers were more likely to achieve biochemically verified abstinence at 6-month follow-up (7.8%) than younger smokers (3.1%) though this difference was not significant. Higher levels of depressed mood and lower levels of perceived stress were associated with a greater likelihood of cessation at both follow-up points, but only for younger smokers. For younger smokers, higher self-efficacy to quit and the presence of a smoking-related disease increased the odds of abstinence. These findings could help guide treatment development for this high-risk group of smokers. C1 [Gregor, Kristin] VA Boston Healthcare Syst, Brockton, MA 02301 USA. [Borrelli, Belinda] Brown Univ, Brown Med Sch, Warren Alpert Med Sch, Ctr Behav & Prevent Med, Providence, RI 02903 USA. RP Gregor, K (reprint author), VA Boston Healthcare Syst, 940 Belmont St, Brockton, MA 02301 USA. EM Kristin.Gregor@va.gov OI Borrelli, Belinda/0000-0002-0859-796X FU NCI NIH HHS [R01 CA74553] NR 43 TC 5 Z9 5 U1 1 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0160-7715 J9 J BEHAV MED JI J. Behav. Med. PD OCT PY 2012 VL 35 IS 5 BP 484 EP 491 DI 10.1007/s10865-011-9376-y PG 8 WC Psychology, Clinical SC Psychology GA 004BK UT WOS:000308654900002 PM 21850514 ER PT J AU Traeger, L O'Cleirigh, C Skeer, MR Mayer, KH Safren, SA AF Traeger, Lara O'Cleirigh, Conall Skeer, Margie R. Mayer, Kenneth H. Safren, Steven A. TI Risk factors for missed HIV primary care visits among men who have sex with men SO JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE HIV; Missed appointments; Adherence; Depression; PTSD; Patient perceptions ID ACTIVE ANTIRETROVIRAL THERAPY; POSTTRAUMATIC-STRESS-DISORDER; HUMAN-IMMUNODEFICIENCY-VIRUS; APPOINTMENT ATTENDANCE; BEHAVIORAL-INHIBITION; INFECTED PATIENTS; SELF-MANAGEMENT; UNITED-STATES; HEALTH-STATUS; MEDICAL-CARE AB Benefits of anti-retroviral therapy (ART) depend on consistent HIV care attendance. However, appointment non-adherence (i.e. missed appointments) is common even in programs that reduce financial barriers. Demographic, health/treatment, and psychosocial contributors to appointment non-adherence were examined among men who have sex with men (MSM) attending HIV primary care. Participants (n = 503) completed questionnaires, and HIV biomarker data were extracted from medical records. At 12 months, records were reviewed to assess HIV primary care appointment non-adherence. Among MSM, 31.2% missed without cancellation at least one appointment during 12-month study period. Independent predictors (P < 0.05) were: low income (OR = 1.87); African American (OR = 3.00) and Hispanic/Latino (OR = 4.31) relative to non-Hispanic White; depression (OR = 2.01); and low expectancy for appointments to prevent/treat infection (OR = 2.38), whereas private insurance (OR = 0.48) and older age (OR = 0.94) predicted lower risk. Low self-efficacy predicted marginal risk (OR = 2.74, P = 0.10). The following did not independently predict risk for non-adherence: education, relationship status, general health, time since HIV diagnosis, ART history, post-traumatic stress disorder, HIV stigma, or supportive clinic staff. Appointment non-adherence is prevalent, particularly among younger and racial/ethnic minority MSM. Socioeconomic barriers, depression and low appointment expectancy and self-efficacy may be targets to increase care engagement. C1 [Traeger, Lara; O'Cleirigh, Conall; Safren, Steven A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Behav Med Serv, Boston, MA 02114 USA. [O'Cleirigh, Conall; Skeer, Margie R.; Mayer, Kenneth H.; Safren, Steven A.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Skeer, Margie R.; Mayer, Kenneth H.] Brown Univ, Sch Med, Providence, RI 02912 USA. RP Traeger, L (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Behav Med Serv, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM LTRAEGER@partners.org FU NIMH NIH HHS [5R01MH068746-05, K24 MH094214, R01 MH068746, R01 MH068746-05, K24MH094214-01]; PHS HHS [H97HA01293] NR 58 TC 19 Z9 19 U1 5 U2 17 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0160-7715 J9 J BEHAV MED JI J. Behav. Med. PD OCT PY 2012 VL 35 IS 5 BP 548 EP 556 DI 10.1007/s10865-011-9383-z PG 9 WC Psychology, Clinical SC Psychology GA 004BK UT WOS:000308654900009 PM 22068878 ER PT J AU White, DL Tavakoli-Tabasi, S Kuzniarek, J Ramsey, DJ El-Serag, HB AF White, Donna L. Tavakoli-Tabasi, Shahriar Kuzniarek, Jill Ramsey, David J. El-Serag, Hashem B. TI Racial Differences in the Association Between Adiposity Measures and the Risk of Hepatitis C-related Liver Disease SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE epidemiology; veterans; infectious diseases; anthropometry; insulin resistance; cirrhosis; obesity; hepatology ID BIOELECTRICAL-IMPEDANCE ANALYSIS; APPENDICULAR BODY-COMPOSITION; NONALCOHOLIC FATTY LIVER; AFRICAN-AMERICANS; BIOCHEMICAL MARKERS; INSULIN-RESISTANCE; VIRUS-INFECTION; PROSPECTIVE MULTICENTER; INTERETHNIC DIFFERENCES; BIOIMPEDANCE ANALYSIS AB Background: African Americans have lower reported likelihood of hepatitis C virus-related cirrhosis than whites. It is unknown whether relative differences in the distribution of adipose tissue, lean mass, and other anthropometric measurements may explain these observed interethnic differences in disease risk. Aim: To evaluate the association between anthropometric measurements and advanced liver disease in a cross-sectional study of African American and white male veterans. Methods: We used the validated FibroSURE-ActiTest to assess hepatic pathology, and direct segmental multichannel bioelectric impedance analysis for anthropometric measurements. Race-stratified logistic regression was employed to evaluate risk of high fibrosis progression rate (FPR) and advanced inflammation (A2 to A3). Results: Among 330 eligible males (59% African American), there were 43 white and 57 African American males with high FPR, and 70 African American and 59 white with advanced inflammation. Percentage body fat (%BF) was a stronger predictor of high FPR risk than was a high body mass index in African Americans [odds ratio (OR)(adj) = 2.08; 95% confidence interval (CI), 0.83-5.23 for highest %BF vs. lowest tertile and ORadj = 1.50; 95% CI, 0.60-3.75 for obese vs. normal body mass index, respectively], but not in whites. Highest lean leg mass was associated with a nonsignificant increased risk of both high FPR and advanced inflammation in African Americans (ORhighFPRadj = 1.73; 95% CI, 0.73-4.10; ORAdvancedinflammationAdj = 1.65; 95% CI, 0.76-3.56) versus a decreased risk of both in whites (ORhighFPRadj = 0.62; 95% CI, 0.21-1.79; ORAdvancedinflammationAdj = 0.58; 95% CI, 0.22-1.48). Conclusions: Interethnic differences in nontraditional anthropometric measurements like %BF suggests their potential role in understanding interethnic differences in hepatitis C virus-related liver disease risk in males. C1 [White, Donna L.; Kuzniarek, Jill; Ramsey, David J.; El-Serag, Hashem B.] Michael E DeBakey VA Med Ctr, Clin Epidemiol & Outcomes Program, Houston VA Hlth Serv Res & Dev Ctr Excellence, Houston, TX USA. [White, Donna L.; El-Serag, Hashem B.] Baylor Coll Med, Dept Med, Sect Gastroenterol & Hepatol, Houston, TX 77030 USA. [White, Donna L.; Kuzniarek, Jill; Ramsey, David J.; El-Serag, Hashem B.] Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Michael E DeBakey Vet Med Ctr, Houston, TX 77030 USA. [Tavakoli-Tabasi, Shahriar] Baylor Coll Med, Dept Med, Sect Infect Dis, Michael E DeBakey Vet Med Ctr, Houston, TX 77030 USA. [Tavakoli-Tabasi, Shahriar] Michael E DeBakey VA Med Ctr, Hepatitis Clin C, Infect Dis Sect, Houston, TX USA. RP White, DL (reprint author), Michael E DeBakey VA Med Ctr, 2002 Holcombe Blvd,MS 152, Houston, TX 77030 USA. EM dwhite1@bcm.edu FU VA Clinical Research and Development Merit Review Award [H-22934]; NIH/National Institute of Diabetes and Digestive and Kidney Diseases [K24 DK081736-01, K01 DK078154-03]; Texas Medical Center Digestive Disease Center [P30 DK56338]; Houston VA HSR&D Center of Excellence FX Supported in part by a VA Clinical Research and Development Merit Review Award (H-22934, PI: H.B.E.-S.), the NIH/National Institute of Diabetes and Digestive and Kidney Diseases (K24 DK081736-01, K01 DK078154-03, PIs, El-Serag and White, respectively), Texas Medical Center Digestive Disease Center (P30 DK56338), and the Houston VA HSR&D Center of Excellence. NR 49 TC 0 Z9 0 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD OCT PY 2012 VL 46 IS 9 BP 779 EP 788 DI 10.1097/MCG.0b013e318266f6eb PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 004TD UT WOS:000308703100013 PM 22955261 ER PT J AU Zhu, AL Sonnenberg, A AF Zhu, Amy L. Sonnenberg, Amnon TI Is Gastric Cancer Again Rising? SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Letter ID HELICOBACTER-PYLORI; TRENDS C1 [Zhu, Amy L.] Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Portland, OR USA. RP Zhu, AL (reprint author), Portland VA Med Ctr, Portland, OR USA. NR 6 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD OCT PY 2012 VL 46 IS 9 BP 804 EP 806 DI 10.1097/MCG.0b013e3182604254 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 004TD UT WOS:000308703100018 PM 22914346 ER PT J AU Waters, JD Sanchez, C Sahin, A Futalan, D Gonda, DD Scheer, JK Akers, J Palanichamy, K Waterman, P Chakravarti, A Weissleder, R Morse, B Marsh, N Furfine, E Chen, CC Carvajal, I Carter, BS AF Waters, J. Dawn Sanchez, Carlos Sahin, Ayguen Futalan, Diahnn Gonda, David D. Scheer, Justin K. Akers, Johnny Palanichamy, Kamalakannan Waterman, Peter Chakravarti, Arnab Weissleder, Ralph Morse, Brent Marsh, Nick Furfine, Eric Chen, Clark C. Carvajal, Irvith Carter, Bob S. TI CT322, a VEGFR-2 antagonist, demonstrates anti-glioma efficacy in orthotopic brain tumor model as a single agent or in combination with temozolomide and radiation therapy SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Glioblastoma; CT322; Vascular endothelial growth factor; Xenograft; Temozolomide; Adnectin (TM) ID ENDOTHELIAL GROWTH-FACTOR; ANTIANGIOGENIC THERAPY; ADNECTIN INHIBITOR; FACTOR RECEPTOR; HUMAN GLIOMAS; IN-VIVO; ANGIOGENESIS; GLIOBLASTOMA; EXPRESSION; CANCER AB Glioblastomas are among the most aggressive human cancers, and prognosis remains poor despite presently available therapies. Angiogenesis is a hallmark of glioblastoma, and the resultant vascularity is associated with poor prognosis. The proteins that mediate angiogenesis, including vascular endothelial growth factor (VEGF) signaling proteins, have emerged as attractive targets for therapeutic development. Since VEGF receptor-2 (VEGFR-2) is thought to be the primary receptor mediating angiogenesis, direct inhibition of this receptor may produce an ideal therapeutic effect. In this context, we tested the therapeutic effect of CT322, a selective inhibitor of VEGFR-2. Using an intracranial murine xenograft model (U87-EGFRvIII-luciferase), we demonstrate that CT322 inhibited glioblastoma growth in vivo and prolonged survival. Of note, the anti-neoplastic effect of CT322 is augmented by the incorporation of temozolomide or temozolomide with radiation therapy. Immunohistochemical analysis of CT322 treated tumors revealed decreased CD31 staining, suggesting that the tumoricidal effect is mediated by inhibition of angiogenesis. These pre-clinical results provide the foundation to further understand long term response and tumor escape mechanisms to anti-angiogenic treatments on EGFR over-expressing glioblastomas. C1 [Waters, J. Dawn; Futalan, Diahnn; Gonda, David D.; Scheer, Justin K.; Akers, Johnny; Chen, Clark C.; Carter, Bob S.] Univ Calif San Diego, Div Neurosurg, La Jolla, CA 92093 USA. [Sanchez, Carlos; Sahin, Ayguen] MGH, MGH HMS Ctr Nervous Syst Repair, Dept Neurosurg, Boston, MA 02114 USA. [Palanichamy, Kamalakannan; Chakravarti, Arnab] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Waterman, Peter; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Mol Imaging, Charlestown, MA 02129 USA. [Morse, Brent; Marsh, Nick; Furfine, Eric; Carvajal, Irvith] Adnexus, Waltham, MA 02453 USA. RP Waters, JD (reprint author), Univ Calif San Diego, Div Neurosurg, 3855 Hlth Sci Dr,0987, La Jolla, CA 92093 USA. EM j.dawn.waters@gmail.com; bobcarter@ucsd.edu RI Chen, Clark/C-8714-2013; Waha, Andreas/J-2950-2014; Palanichamy, Kamalakannan/E-3807-2011 OI Chen, Clark/0000-0001-6258-9277; FU Adnexus, a Bristol-Myers Squibb RD Company FX Grant Support: Adnexus, a Bristol-Myers Squibb R&D Company. NR 36 TC 7 Z9 7 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD OCT PY 2012 VL 110 IS 1 BP 37 EP 48 DI 10.1007/s11060-012-0948-7 PG 12 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 004CA UT WOS:000308656500005 PM 22875706 ER PT J AU Chi, AS Batchelor, TT Dias-Santagata, D Borger, D Stiles, CD Wang, DL Curry, WT Wen, PY Ligon, KL Ellisen, L Louis, DN Iafrate, AJ AF Chi, Andrew S. Batchelor, Tracy T. Dias-Santagata, Dora Borger, Darrell Stiles, Charles D. Wang, Daphne L. Curry, William T. Wen, Patrick Y. Ligon, Keith L. Ellisen, Leif Louis, David N. Iafrate, A. John TI Prospective, high-throughput molecular profiling of human gliomas SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Tumor genotyping; Molecular profiling; Biomarker; Glioblastoma; Glioma ID INTEGRATED GENOMIC ANALYSIS; GIANT-CELL GLIOBLASTOMAS; LUNG-CANCER; ACTIVATING MUTATIONS; SOMATIC MUTATIONS; TYROSINE KINASE; HUMAN BRAIN; GENE; AMPLIFICATION; TEMOZOLOMIDE AB Gliomas consist of multiple histologic and molecular subtypes with different clinical phenotypes and responsiveness to treatment. However, enrollment criteria for clinical trials still largely do not take into account these underlying molecular differences. We have incorporated a high-throughput tumor genotyping program based on the ABI SNaPshot platform as well as other molecular diagnostic tests into the standard evaluation of glioma patients in order to assess whether prospective molecular profiling would allow rational patient selection onto clinical trials. From 218 gliomas we prospectively collected SNaPshot genotyping data on 68 mutated loci from 15 key cancer genes along with data from clinical assays for gene amplification (EGFR, PDGFRA, MET), 1p/19q co-deletion and MGMT promoter methylation. SNaPshot mutations and focal gene amplifications were detected in 38.5 and 47.1 % of glioblastomas, respectively. Genetic alterations in EGFR, IDH1 and PIK3CA closely matched frequencies reported in recent studies. In addition, we identified events that are rare in gliomas although are known driver mutations in other cancer types, such as mutations of AKT1, BRAF and KRAS. Patients with genetic alterations that activate signaling pathways were enrolled onto genetically selective clinical trials for malignant glioma as well as for other solid cancers. High-throughput molecular profiling incorporated into the routine clinical evaluation of glioma patients may enable the rational selection of patients for targeted therapy clinical trials and thereby improve the likelihood that such trials succeed. C1 [Chi, Andrew S.; Batchelor, Tracy T.; Wang, Daphne L.] Massachusetts Gen Hosp, Dept Neurol, Stephen E & Catherine Pappas Ctr Neurooncol, Ctr Canc, Boston, MA 02114 USA. [Dias-Santagata, Dora; Borger, Darrell; Ellisen, Leif; Iafrate, A. John] Massachusetts Gen Hosp, Ctr Canc, Translat Res Lab, Boston, MA 02114 USA. [Dias-Santagata, Dora; Louis, David N.; Iafrate, A. John] Massachusetts Gen Hosp, Ctr Canc, Dept Pathol, Boston, MA 02114 USA. [Stiles, Charles D.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Curry, William T.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Wen, Patrick Y.] Brigham & Womens Hosp, Ctr Neurooncol, Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. [Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Ligon, Keith L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Mol Oncol Pathol,Dana Farber Canc Inst, Boston, MA 02115 USA. [Ligon, Keith L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Chi, AS (reprint author), Massachusetts Gen Hosp, Dept Neurol, Stephen E & Catherine Pappas Ctr Neurooncol, Ctr Canc, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM chi.andrew@mgh.harvard.edu FU Joan Ambriz American Brain Tumor Association Basic Research Fellowship; Ben and Catherine Ivy Foundation FX Preliminary data of this manuscript was presented at the 2011 American Association of Neurology Annual Meeting in Honolulu, Hawaii. Andrew S. Chi is supported by a Joan Ambriz American Brain Tumor Association Basic Research Fellowship and an Early Career research award from the Ben and Catherine Ivy Foundation. Ethical Standards: All results were obtained from the medical record of patients and collected in an IRB-approved patient database. Molecular testing was performed as part of routine medical care in CLIA-certified clinical laboratories. All molecular tests comply with the current laws of the USA. NR 36 TC 23 Z9 24 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD OCT PY 2012 VL 110 IS 1 BP 89 EP 98 DI 10.1007/s11060-012-0938-9 PG 10 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 004CA UT WOS:000308656500010 PM 22821383 ER PT J AU Cipriani, S Desjardins, CA Burdett, TC Xu, YH Xu, K Schwarzschild, MA AF Cipriani, Sara Desjardins, Cody A. Burdett, Thomas C. Xu, Yuehang Xu, Kui Schwarzschild, Michael A. TI Protection of dopaminergic cells by urate requires its accumulation in astrocytes SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE cell viability; HPLC; MES 23; 5 cells; transgenic; transporter; uricase ID ORGANIC ANION TRANSPORTERS; PARKINSONS-DISEASE; URIC-ACID; ABLUMINAL MEMBRANE; METABOLITES; NEURONS; PREDICTOR; TOXICITY; DAMAGE; MODEL AB Urate is the end product of purine metabolism and a major antioxidant circulating in humans. Recent data link higher levels of urate with a reduced risk of developing Parkinsons disease and with a slower rate of its progression. In this study, we investigated the role of astrocytes in urate-induced protection of dopaminergic cells in a cellular model of Parkinsons disease. In mixed cultures of dopaminergic cells and astrocytes oxidative stress-induced cell death and protein damage were reduced by urate. By contrast, urate was not protective in pure dopaminergic cell cultures. Physical contact between dopaminergic cells and astrocytes was not required for astrocyte-dependent rescue as shown by conditioned medium experiments. Urate accumulation in dopaminergic cells and astrocytes was blocked by pharmacological inhibitors of urate transporters expressed differentially in these cells. The ability of a urate transport blocker to prevent urate accumulation into astroglial (but not dopaminergic) cells predicted its ability to prevent dopaminergic cell death. Transgenic expression of uricase reduced urate accumulation in astrocytes and attenuated the protective influence of urate on dopaminergic cells. These data indicate that urate might act within astrocytes to trigger release of molecule(s) that are protective for dopaminergic cells. C1 [Cipriani, Sara; Desjardins, Cody A.; Burdett, Thomas C.; Xu, Yuehang; Xu, Kui; Schwarzschild, Michael A.] Massachusetts Gen Hosp, Mol Neurobiol Lab, MassGen Inst Neurodegenerat Dis, Boston, MA 02129 USA. RP Cipriani, S (reprint author), Massachusetts Gen Hosp, Mol Neurobiol Lab, MassGen Inst Neurodegenerat Dis, 114 16th St, Boston, MA 02129 USA. EM pattona80@hotmail.com FU American Parkinson Disease Association; US National Institutes of Health [R21NS058324, K24NS060991]; US Department of Defense [W81XWH-11-1-0150] FX This work was supported by the American Parkinson Disease Association, US National Institutes of Health grants R21NS058324, K24NS060991 and the US Department of Defense grant W81XWH-11-1-0150. MES 23.5 cells, transgenic UOx mice and technical advice were kindly provided by Weidong Le, Ken Rock, and Hajime Kono. We would like to thank Dr. Mount from Brigham and Women's Hospital, Boston, for his thoughtful comments regarding urate transporter experiments. The authors declare no competing financial interests. NR 39 TC 13 Z9 14 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 2012 VL 123 IS 1 BP 172 EP 181 DI 10.1111/j.1471-4159.2012.07820.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 003SO UT WOS:000308631800015 PM 22671773 ER PT J AU Collins, EG Halabi, S Langston, M Schnell, T Tobin, MJ Laghi, F AF Collins, Eileen G. Halabi, Sahar Langston, Mathew Schnell, Timothy Tobin, Martin J. Laghi, Franco TI Sexual Dysfunction in Men with COPD: Impact on Quality of Life and Survival SO LUNG LA English DT Article DE Endocrine; Erectile dysfunction; Testosterone; Sexuality; Aging; Outcome ID OBSTRUCTIVE PULMONARY-DISEASE; ERECTILE DYSFUNCTION; DEPRESSIVE SYMPTOMS; INTERNATIONAL INDEX; CARDIOVASCULAR-DISEASE; TOTAL TESTOSTERONE; PENILE ERECTION; PREVALENCE; IMPOTENCE; VALIDATION AB Most patients with chronic obstructive pulmonary disease (COPD) are middle-aged or older, and by definition all have a chronic illness. Aging and chronic illness decrease sexual interest, sexual function, and testosterone levels. To date, researchers have not simultaneously explored prevalence, risk factors, and impact of sexual dysfunctions on quality of life and survival in men with COPD. We tested three hypotheses: First, sexual dysfunctions, including erectile dysfunction, are highly prevalent and impact negatively the quality of life of those with COPD. Second, gonadal state is a predictor of erectile dysfunction. Third, erectile dysfunction, a potential maker of systemic atherosclerosis, is a risk factor for mortality in men with COPD. In this prospective study, sexuality was assessed in 90 men with moderate-to-severe COPD (40 hypogonadal) by questionnaire. Testosterone levels, comorbidities, dyspnea, depressive symptoms, and survival (4.8 years median follow-up) were recorded. Seventy-four percent of patients had at least one sexual dysfunction, with erectile dysfunction being the most common (72 %). Most were dissatisfied with their current and expected sexual function. Severity of COPD was equivalent in patients with and without erectile dysfunction. Low testosterone, depressive symptoms, and presence of partner were independently associated with erectile dysfunction. Severity of lung disease and comorbidities, but not erectile dysfunction, were independently associated with mortality (p = 0.006). Sexual dysfunctions, including erectile dysfunction, were highly prevalent and had a negative impact on quality of life in men with COPD. In addition, gonadal state was an independent predictor of erectile dysfunction. Finally, erectile dysfunction was not associated with all-cause mortality. C1 [Halabi, Sahar; Langston, Mathew; Schnell, Timothy; Tobin, Martin J.; Laghi, Franco] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. [Collins, Eileen G.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv, Hines, IL 60141 USA. [Collins, Eileen G.] Univ Illinois, Coll Nursing, Chicago, IL USA. [Langston, Mathew; Schnell, Timothy; Tobin, Martin J.; Laghi, Franco] Loyola Univ, Div Pulm & Crit Care Med, Maywood, IL 60153 USA. RP Laghi, F (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, 111 N 5th Ave & Roosevelt Rd, Hines, IL 60141 USA. EM flaghi@lumc.edu FU AMVETS; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development Rehabilitation Research and Development Service FX This work was supported in part by grants from AMVETS and the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development Rehabilitation Research and Development Service. NR 64 TC 12 Z9 14 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0341-2040 J9 LUNG JI Lung PD OCT PY 2012 VL 190 IS 5 BP 545 EP 556 DI 10.1007/s00408-012-9398-4 PG 12 WC Respiratory System SC Respiratory System GA 008PG UT WOS:000308968400010 PM 22752718 ER PT J AU Bryant, A Fernandez-Lamothe, A Kuppermann, M AF Bryant, Allison Fernandez-Lamothe, Ana Kuppermann, Miriam TI Attitudes Toward Birth Spacing Among Low-Income, Postpartum Women: A Qualitative Analysis SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Article DE Birth spacing; Low income; Postpartum; Qualitative research ID INTERPREGNANCY INTERVAL; PERINATAL OUTCOMES; UNITED-STATES; RISK; DEPLETION; PREGNANCIES; HEALTH; WHITE AB To explore attitudes about birth spacing among low-income, recently postpartum women, using qualitative methods, seven focus groups among postpartum women were conducted, probing knowledge and attitudes related to desired birth spacing. Transcripts of the discussions were reviewed and coded for salient themes using a Grounded Theory approach. In regards to whether to pursue pregnancy in the future, major themes included the availability of adequate resources, current family composition and the role of partners. With respect to when to have a next pregnancy, themes centered around the desire for particular intervals between siblings. Discussions of the effect of spacing on the health of the mother or child did not emerge frequently. Themes underlying postpartum women's desire for particular birth spacing are varied, but social and family considerations seem to predominate over concerns or knowledge about potential health effects. Improving women's knowledge about these consequences could lead to lowering the incidence of short interpregnancy intervals, known to be associated with adverse perinatal outcomes. C1 [Bryant, Allison] Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA. [Fernandez-Lamothe, Ana; Kuppermann, Miriam] Univ Calif San Francisco, Dept Obstet, San Francisco, CA 94118 USA. [Fernandez-Lamothe, Ana; Kuppermann, Miriam] Univ Calif San Francisco, Dept Gynecol, San Francisco, CA 94118 USA. [Fernandez-Lamothe, Ana; Kuppermann, Miriam] Univ Calif San Francisco, Dept Reprod Sci, San Francisco, CA 94118 USA. [Kuppermann, Miriam] Univ Calif San Francisco, Med Effectiveness Res Ctr Div Populat, San Francisco, CA 94118 USA. RP Bryant, A (reprint author), Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, 55 Fruit St,Founders 4, Boston, MA 02114 USA. EM abryant@partners.org FU NCRR NIH HHS [KL2 RR024130] NR 21 TC 8 Z9 8 U1 0 U2 9 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1092-7875 J9 MATERN CHILD HLTH J JI Matern. Child Health J. PD OCT PY 2012 VL 16 IS 7 BP 1440 EP 1446 DI 10.1007/s10995-011-0911-9 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 006LT UT WOS:000308821400011 PM 22057657 ER PT J AU Pipa, G Chen, Z Neuenschwander, S Lima, B Brown, EN AF Pipa, Gordon Chen, Zhe Neuenschwander, Sergio Lima, Bruss Brown, Emery N. TI Mapping of Visual Receptive Fields by Tomographic Reconstruction SO NEURAL COMPUTATION LA English DT Article ID TIME-RESCALING THEOREM; CATS STRIATE CORTEX; TRAIN DATA-ANALYSIS; MACAQUE V1; DIRECTION SELECTIVITY; NEURAL SPIKING; NEURONS; CELLS; ORIENTATION; PLASTICITY AB The moving bar experiment is a classic paradigm for characterizing the receptive field (RF) properties of neurons in primary visual cortex (V1). Current approaches for analyzing neural spiking activity recorded from these experiments do not take into account the point-process nature of these data and the circular geometry of the stimulus presentation. We present a novel analysis approach to mapping V1 receptive fields that combines point-process generalized linear models (PPGLM) with tomographic reconstruction computed by filtered-back projection. We use the method to map the RF sizes and orientations of 251 V1 neurons recorded from two macaque monkeys during a moving bar experiment. Our cross-validated goodness-of-fit analyses show that the PPGLM provides a more accurate characterization of spike train data than analyses based on rate functions computed by the methods of spike-triggered averages or first-order Wiener-Volterra kernel. Our analysis leads to a new definition of RF size as the spatial area over which the spiking activity is significantly greater than baseline activity. Our approach yields larger RF sizes and sharper orientation tuning estimates. The tomographic reconstruction paradigm further suggests an efficient approach to choosing the number of directions and the number of trials per direction in designing moving bar experiments. Our results demonstrate that standard tomographic principles for image reconstruction can be adapted to characterize V1 RFs and that two fundamental properties, size and orientation, may be substantially different from what is currently reported. C1 [Pipa, Gordon; Chen, Zhe; Brown, Emery N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. [Pipa, Gordon] Univ Osnabruck, Inst Cognit Sci, D-49074 Osnabruck, Germany. [Pipa, Gordon; Neuenschwander, Sergio; Lima, Bruss] Max Planck Inst Brain Res, D-60528 Frankfurt, Germany. [Chen, Zhe; Brown, Emery N.] MIT, Harvard Mit Div Hlth Sci & Technol, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Pipa, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. EM gpipa@uos.de; zhechen@mit.edu; neuenschwand@mpih-frankfurt.mpg.de; lima@mpih-frankfurt.mpg.de; enb@neurostat.mit.edu RI Pipa, Gordon/M-1813-2014; Lima, Bruss/I-9164-2016; OI Pipa, Gordon/0000-0002-3416-2652; Lima, Bruss/0000-0001-6865-2900; Chen, Zhe/0000-0002-6483-6056 FU U.S. National Institutes of Health [DP1-OD003646]; European Union [240763] FX We thank two anonymous reviewers for valuable comments. This work was supported by the U.S. National Institutes of Health, grant DP1-OD003646 (to E.N.B.), and the European Union, FP7-1CT, grant 240763 (to G.P.). Some preliminary results were presented in COSYNE'09, Salt Lake City, Utah (Pipa, Chen, Neuenschwander, Lima, & Brown, 2009). NR 54 TC 3 Z9 3 U1 0 U2 7 PU MIT PRESS PI CAMBRIDGE PA ONE ROGERS ST, CAMBRIDGE, MA 02142-1209 USA SN 0899-7667 EI 1530-888X J9 NEURAL COMPUT JI Neural Comput. PD OCT PY 2012 VL 24 IS 10 BP 2543 EP 2578 DI 10.1162/NECO_a_00334 PG 36 WC Computer Science, Artificial Intelligence; Neurosciences SC Computer Science; Neurosciences & Neurology GA 000XG UT WOS:000308423500001 PM 22734491 ER PT J AU Hansen, L Press, N Rosenkranz, SJ Baggs, JG Kendall, J Kerber, A Williamson, A Chesnutt, MS AF Hansen, Lissi Press, Nancy Rosenkranz, Susan J. Baggs, Judith Gedney Kendall, Judith Kerber, Amanda Williamson, Angel Chesnutt, Mark S. TI Life-sustaining treatment decisions in the ICU for patients with ESLD: A prospective investigation SO RESEARCH IN NURSING & HEALTH LA English DT Article DE intensive care; qualitative research; decision-making; liver diseases; life support care ID INTENSIVE-CARE-UNIT; CRITICALLY-ILL; QUALITATIVE DESCRIPTION; FAMILY SATISFACTION; PALLIATIVE CARE; END; SUPPORT; WITHDRAWAL; COMMUNICATION; PERSPECTIVES AB We conducted a prospective study in the ICU of life-sustaining treatment and comfort care decisions over time in patients with end-stage liver disease (ESLD) from the perspectives of patients, family members, and healthcare professionals. Six patients with ESLD, 19 family members, and 122 professionals participated. The overarching theme describing the decision-making process was on the train. Four sub-themes positioned patients and family members as passengers with limited control, unable to fully understand the decision-making process. Findings suggest that including patients and family members in non-immediate life-saving decisions and verifying early on their understanding may help to improve the decision-making process. (c) 2012 Wiley Periodicals, Inc. Res Nurs Health 35:518532, 2012 C1 [Hansen, Lissi; Press, Nancy; Rosenkranz, Susan J.; Baggs, Judith Gedney; Kendall, Judith; Kerber, Amanda; Williamson, Angel; Chesnutt, Mark S.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Chesnutt, Mark S.] Portland VA Med Ctr, Portland, OR USA. RP Hansen, L (reprint author), Oregon Hlth & Sci Univ, SN 6S,3455 SWUS Vet Hosp Rd, Portland, OR 97239 USA. FU National Institute of Nursing Research [R21 NR009845]; Portland VA Medical Center, Portland, Oregon FX The study was funded by grant R21 NR009845 from the National Institute of Nursing Research, Lissi Hansen (PI). This study is the result of work supported by resources from the Portland VA Medical Center, Portland, Oregon. Neither the NIH nor the Department of Veterans Affairs had a role in the conduct of the study, in the collection, management, analysis, or interpretation of data, or in the preparation of the manuscript. 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 U.S. Government. The authors thank the patients, family members, and healthcare professionals for participating in the study and sharing their perspectives and the different specialties for their support of the study. NR 58 TC 3 Z9 3 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-6891 J9 RES NURS HEALTH JI Res. Nurs. Health PD OCT PY 2012 VL 35 IS 5 BP 518 EP 532 DI 10.1002/nur.21488 PG 15 WC Nursing SC Nursing GA 004YO UT WOS:000308717600008 PM 22581585 ER PT J AU Kikinis, Z Asami, T Bouix, S Finn, CT Ballinger, T Tworog-Dube, E Kucherlapati, R Kikinis, R Shenton, ME Kubicki, M AF Kikinis, Z. Asami, T. Bouix, S. Finn, C. T. Ballinger, T. Tworog-Dube, E. Kucherlapati, R. Kikinis, R. Shenton, M. E. Kubicki, M. TI Reduced fractional anisotropy and axial diffusivity in white matter in 22q11.2 deletion syndrome: A pilot study SO SCHIZOPHRENIA RESEARCH LA English DT Article DE 22q11.2 deletion syndrome (22q11.2DS); Schizophrenia; Diffusion Tensor Magnetic Resonance Imaging (DT-MRI); Fractional anisotropy (FA); Axial and radial diffusivity; Tract-Based Spatial Statistics (TBSS) ID CARDIO-FACIAL SYNDROME; RADIAL DIFFUSIVITY; VELOCARDIOFACIAL SYNDROME; SPATIAL-STATISTICS; VOXELWISE ANALYSIS; SCHIZOPHRENIA; TENSOR; ADULTS; BRAIN; CONNECTIVITY AB Individuals with 22q11.2 deletion syndrome (22q11.2DS) evince a 30% incidence of schizophrenia. We compared the white matter (WM) of 22q11.2DS patients without schizophrenia to a group of matched healthy controls using Tract-Based-Spatial-Statistics (TBSS). We found localized reduction of Fractional Anisotropy (FA) and Axial Diffusivity (AD; measure of axonal integrity) in WM underlying the left parietal lobe. No changes in Radial Diffusivity (RD; measure of myelin integrity) were observed. Of note, studies in chronic schizophrenia patients report reduced FA, no changes in AD, and increases in RD in WM. Our findings suggest different WM microstructural pathology in 22q11.2DS than in patients with schizophrenia. (C) 2012 Elsevier B.V. All rights reserved. C1 [Kikinis, Z.; Asami, T.; Bouix, S.; Ballinger, T.; Shenton, M. E.; Kubicki, M.] Harvard Univ, Psychiat Neuroimaging Lab, Dept Psychiat, Brigham & Womens Hosp,Med Sch, Boston, MA 02115 USA. [Finn, C. T.] Dartmouth Hitchcock Med Ctr, Dept Psychiat, Lebanon, NH 03766 USA. [Tworog-Dube, E.] Harvard Univ, Dept Med, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Kikinis, R.; Shenton, M. E.; Kubicki, M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Surg Planning Lab,Dept Radiol, Boston, MA 02115 USA. [Shenton, M. E.; Kubicki, M.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Clin Neurosci Div,Lab Neurosci,Dept Psychiat, Brockton, MA 02401 USA. RP Kikinis, Z (reprint author), Harvard Univ, Psychiat Neuroimaging Lab, Dept Psychiat, Brigham & Womens Hosp,Med Sch, 1249 Boylston St, Boston, MA 02115 USA. EM zora@bwh.harvard.edu FU NARSAD Young Investigator Award; Department of Veterans Affairs Merit Awards; VA Schizophrenia Center grant; National Institute of Mental Health [R01 MH 50740, K05 MH 070047, R01MH082918]; NIH Mental Health Centers for Interventional Development and Applied Research-CIDAR [P50 MH 080272]; National Alliance for Medical Image Computing [NAMIC - U54 EB005149]; Neuroimage Analysis Center (NAC) [P41 RR 13218]; Department of Radiology at BWH; NCRR FX This work was supported, in part, by a NARSAD Young Investigator Award (ZK), by the Department of Veterans Affairs Merit Awards (MES), by a VA Schizophrenia Center grant (MES), by grants from the National Institute of Mental Health, including a Career Reentry Supplement (ZK) on R01 MH 50740 (MES), a K05 MH 070047 (MES), R01MH082918 (SB), and a NIH Mental Health Centers for Interventional Development and Applied Research-CIDAR-P50 MH 080272 (MES, MK), and, finally, by the National Alliance for Medical Image Computing (NAMIC - U54 EB005149 (RK, also MK, MES)), and a Neuroimage Analysis Center (NAC) P41 RR 13218 grant (RK) funded by NCRR. The funding source had no role in the study design, nor in the collection, analysis or interpretation of data, writing of the paper, or in the decision for publication.; We thank Dr. Ferenc Jolesz and the Department of Radiology at BWH for providing some of the funding for images for this pilot study. NR 52 TC 16 Z9 16 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 2012 VL 141 IS 1 BP 35 EP 39 DI 10.1016/j.schres.2012.06.032 PG 5 WC Psychiatry SC Psychiatry GA 004VK UT WOS:000308709100007 PM 22863550 ER PT J AU Zhang, XY Chen, DC Xiu, MH Hui, L Liu, HB Luo, XG Zuo, LJ Zhang, HP Kosten, TA Kosten, TR AF Zhang, Xiang Yang Chen, Da Chun Xiu, Mei Hong Hui, Li Liu, Haibo Luo, Xingguang Zuo, Lingjun Zhang, Huiping Kosten, Therese A. Kosten, Thomas R. TI Association of functional dopamine-beta-hydroxylase (DBH) 19 bp insertion/deletion polymorphism with smoking severity in male schizophrenic smokers SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Dopamine beta-hydroxylase; Smoking; Nicotine; Genotype; Association ID YOUNG-WOMEN SMOKE; TOBACCO SMOKING; GENE DBH; PSYCHOLOGICAL CHARACTERISTICS; NICOTINE DEPENDENCE; METABOLIC ENZYMES; CONSUMPTION; BEHAVIOR; LINKAGE; VARIANT AB Recent evidence suggests that a dopamine beta-hydroxylase (DBH) polymorphism may play a role in determining an individual's predisposition to developing nicotine dependence. The mechanism for such an association may reflect nicotine's mediation of drug reward in the brain through actions on dopamine, a key mediator of drug reward. Because schizophrenia patients have usually high rates of nicotine use, they are a model group to study such an association. In this study, we hypothesized that the functional polymorphism of DBH (D beta H5'-Ins/Del) was associated with smoking in patients with schizophrenia. This polymorphism was genotyped in 636 chronic male schizophrenia (smoker/nonsmoker=490/146) and 396 male controls (smoker/nonsmoker=231/165) using a case-control design. The cigarettes smoked per day (CPD) and smoking behaviors were evaluated by clinician-administered questionnaires and the Fagerstrom Test for Nicotine Dependence (FTND). The results showed no significant differences in DBH 5'-Ins/Del genotype and allele distributions between the patients and healthy controls or between smokers and nonsmokers in either patients or healthy controls alone. However, schizophrenic smokers with the Del allele smoked fewer cigarettes each day and had lower FTND score than those with Ins/Ins genotype. These results suggest that the DBH 5'-Ins/Del polymorphism may influence smoking severity among schizophrenic smokers. (C) 2012 Elsevier B.V. All rights reserved. C1 [Zhang, Xiang Yang] Chinese Acad Sci, Inst Psychol, Beijing 100101, Peoples R China. [Zhang, Xiang Yang; Kosten, Therese A.; Kosten, Thomas R.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Zhang, Xiang Yang; Chen, Da Chun; Xiu, Mei Hong; Hui, Li; Liu, Haibo; Kosten, Thomas R.] Peking Univ, Ctr Biol Psychiat, Beijing HuiLongGuan Hosp, Beijing 100871, Peoples R China. [Luo, Xingguang; Zuo, Lingjun; Zhang, Huiping] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. RP Zhang, XY (reprint author), VA Med Ctr, Res Bldg 109,Room 130,2002 Holcombe Blvd, Houston, TX 77030 USA. EM xyzhang@bcm.edu; kosten@bcm.edu FU Stanley Medical Research Institute [03T-459, 05T-726]; Department of Veterans Affairs [VISN 16]; Mental Illness Research, Education and Clinical Center (MIRECC); United States National Institute of Health [P50-DA18827, K05-DA0454, U01-MH79639] FX Funding for this study was provided by grants from the Stanley Medical Research Institute (03T-459 and 05T-726), and the Department of Veterans Affairs, VISN 16, Mental Illness Research, Education and Clinical Center (MIRECC), United States National Institute of Health K05-DA0454, P50-DA18827 and U01-MH79639. These sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 47 TC 5 Z9 6 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 2012 VL 141 IS 1 BP 48 EP 53 DI 10.1016/j.schres.2012.07.011 PG 6 WC Psychiatry SC Psychiatry GA 004VK UT WOS:000308709100009 PM 22871345 ER PT J AU Francis, AN Seidman, LJ Jabbar, GA Mesholam-Gately, R Thermenos, HW Juelich, R Proal, AC Shenton, M Kubicki, M Mathew, I Keshavan, M DeLisi, LE AF Francis, Alan N. Seidman, Larry J. Jabbar, Gul A. Mesholam-Gately, Raquelle Thermenos, Heidi W. Juelich, Richard Proal, Ashley C. Shenton, Martha Kubicki, Marek Mathew, Ian Keshavan, Matcheri DeLisi, Lynn E. TI Alterations in brain structures underlying language function in young adults at high familial risk for schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Familial high risk; Brain anatomy; Language; Asymmetry ID INFERIOR FRONTAL GYRUS; PREFRONTAL CORTEX; GENETIC RISK; 1ST-EPISODE SCHIZOPHRENIA; WORD RECOGNITION; VERBAL FLUENCY; RELATIVES; MATTER; FMRI; MRI AB Introduction: Neuroanatomical and cognitive alterations typical of schizophrenia (SZ) patients are observed to a lesser extent in their adolescent and adult first-degree relatives, likely reflecting neurodevelopmental abnormalities associated with genetic risk for the illness. The anatomical pathways for language are hypothesized to be abnormal and to underlie the positive symptoms of schizophrenia. Examining non-psychotic relatives at high familial risk (FHR) for schizophrenia may clarify if these deficits represent trait markers associated with genetic vulnerability, rather than specific markers resulting from the pathological process underlying schizophrenia. Methods: T1 MRI scans from a 3T Siemens scanner of young adult FHR subjects (N=46) and controls with no family history of illness (i.e. at low genetic risk LRC; N=31) were processed using FreeSurfer 5.0. We explored volumetric and lateralization alterations in regions associated with language processing. An extensive neuropsychological battery of language measures was administered. Results: No significant differences were observed between groups on any language measures. Controlling intra-cranial volume, significantly smaller left pars triangularis (PT) (p<0.01) and right pars orbitalis (PO) (p<0.01) volumes and reversal of the L> R pars orbitalis (p<0.001) lateralization were observed in FHR subjects. In addition, the L pars triangularis and R pars orbitalis correlated with performance on tests of linguistic function in the FHR group. Conclusions: Reduced volume and reversed structural asymmetry in language-related regions hypothesized to be altered in SZ are also found in first degree relatives at FHR, despite normal language performance. To clarify if these findings are endophenotypes for Sz, future studies would need to be performed of ill and well family members no longer within the age range of risk for illness to show these deficits segregate with schizophrenia within families. Moreover, measures of complex language need to be studied to determine if FHR individuals manifest impairments in some aspects of language function. Published by Elsevier B.V. C1 [Jabbar, Gul A.; Proal, Ashley C.; Shenton, Martha; Kubicki, Marek; DeLisi, Lynn E.] Boston Healthcare Syst, Brockton, MA USA. [Francis, Alan N.; Seidman, Larry J.; Mesholam-Gately, Raquelle; Thermenos, Heidi W.; Mathew, Ian; Keshavan, Matcheri] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. [Seidman, Larry J.; Thermenos, Heidi W.; Juelich, Richard] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Shenton, Martha; Kubicki, Marek] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP DeLisi, LE (reprint author), VA Boston Healthcare Syst, Bldg 2 2-2-B,940 Belmont Ave, Brockton, MA USA. EM DeLisi76@AOL.com FU Commonwealth Research Center of the Massachusetts Department of Mental Health [SCDMH82101008006]; [NIMH-R21MH083205]; [MH 64023]; [MH78113] FX This project was funded by NIMH-R21MH083205 (LED), MH 64023 and MH78113 (MSK), and the Commonwealth Research Center of the Massachusetts Department of Mental Health, SCDMH82101008006 (LJS). NR 61 TC 18 Z9 18 U1 1 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 2012 VL 141 IS 1 BP 65 EP 71 DI 10.1016/j.schres.2012.07.015 PG 7 WC Psychiatry SC Psychiatry GA 004VK UT WOS:000308709100012 PM 22892286 ER PT J AU Tarbox, SI Brown, LH Haas, GL AF Tarbox, Sarah I. Brown, Leslie H. Haas, Gretchen L. TI Diagnostic specificity of poor premorbid adjustment: Comparison of schizophrenia, schizoaffective disorder, and mood disorder with psychotic features SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Development; First-episode; Prediction; Psychosis; Schizophrenia-spectrum; Social functioning ID 1ST-EPISODE SCHIZOPHRENIA; VALIDITY; SCALE AB Individuals with schizophrenia have significant deficits in premorbid social and academic adjustment compared to individuals with non-psychotic diagnoses. However, it is unclear how severity and developmental trajectory of premorbid maladjustment compare across psychotic disorders. This study examined the association between premorbid functioning (in childhood, early adolescence, and late adolescence) and psychotic disorder diagnosis in a first-episode sample of 105 individuals: schizophrenia (n = 68), schizoaffective disorder (n = 22), and mood disorder with psychotic features (n = 15). Social and academic maladjustment was assessed using the Cannon-Spoor Premorbid Adjustment Scale. Worse social functioning in late adolescence was associated with higher odds of schizophrenia compared to odds of either schizoaffective disorder or mood disorder with psychotic features, independently of child and early adolescent maladjustment. Greater social dysfunction in childhood was associated with higher odds of schizoaffective disorder compared to odds of schizophrenia. Premorbid decline in academic adjustment was observed for all groups, but did not predict diagnosis at any stage of development. Results suggest that social functioning is disrupted in the premorbid phase of both schizophrenia and schizoaffective disorder, but remains fairly stable in mood disorders with psychotic features. Disparities in the onset and time course of social dysfunction suggest important developmental differences between schizophrenia and schizoaffective disorder. (C) 2012 Elsevier B.V. All rights reserved. C1 [Tarbox, Sarah I.; Brown, Leslie H.; Haas, Gretchen L.] Univ Pittsburgh, Western Psychiat Inst & Clin, Med Ctr, Pittsburgh, PA 15213 USA. [Haas, Gretchen L.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr MIRECC VISN4, Pittsburgh, PA USA. RP Tarbox, SI (reprint author), Connecticut Mental Hlth Ctr, PRIME Res Clin, 34 Pk St,B-38, New Haven, CT 06519 USA. EM sarah.tarbox@yale.edu FU NIH/NCRR/GCRC [M01 RR00056]; [MH45156]; [MH84053]; [MH48492]; [c UL1 RR024153] FX This work was supported by MH45156 and MH84053 (PI: D. Lewis), MH48492 (PI: G. L. Haas), and the c UL1 RR024153 and NIH/NCRR/GCRC Grant M01 RR00056. We thank Drs. Raymond Cho, MD, Gretchen Haas PhD, and Konasale Prasad, MD, and the clinical core staff of the Center for the Neuroscience of Mental Disorders (MH45156, MH084053, David Lewis, MD, Director) for their assistance in diagnostic, psychosocial, and psychopathological assessments. We thank James Luther, MA, and Barbara Hanusa, PhD, for their statistical consultation and assistance with parameter estimation for the logistic regression models. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. NR 21 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 2012 VL 141 IS 1 BP 91 EP 97 DI 10.1016/j.schres.2012.07.008 PG 7 WC Psychiatry SC Psychiatry GA 004VK UT WOS:000308709100016 PM 22858353 ER PT J AU Abbs, B Achalia, RM Adelufosi, AO Aktener, AY Beveridge, NJ Bhakta, SG Blackman, RK Bora, E Byun, MS Cabanis, M Carrion, R Castellani, CA Chow, TJ Dmitrzak-Weglarz, M Gayer-Anderson, C Gomes, FV Haut, K Hori, H Kantrowitz, JT Kishimoto, T Lee, FHF Lin, A Palaniyappan, L Quan, MN Rubio, MD de Azua, SR Sahoo, S Strauss, GP Szczepankiewicz, A Thompson, AD Trotta, A Tully, LM Uchida, H Velthorst, E Young, JW O'Shea, A DeLisi, LE AF Abbs, Brandon Achalia, Rashmin M. Adelufosi, Adegoke O. Aktener, Ahmet Yigit Beveridge, Natalie J. Bhakta, Savita G. Blackman, Rachael K. Bora, Emre Byun, M. S. Cabanis, Maurice Carrion, Ricardo Castellani, Christina A. Chow, Tze Jen Dmitrzak-Weglarz, M. Gayer-Anderson, Charlotte Gomes, Felipe V. Haut, Kristen Hori, Hiroaki Kantrowitz, Joshua T. Kishimoto, Taishiro Lee, Frankie H. F. Lin, Ashleigh Palaniyappan, Lena Quan, Meina Rubio, Maria D. de Azua, Sonia Ruiz Sahoo, Saddichha Strauss, Gregory P. Szczepankiewicz, Aleksandra Thompson, Andrew D. Trotta, Antonella Tully, Laura M. Uchida, Hiroyuki Velthorst, Eva Young, Jared W. O'Shea, Anne DeLisi, Lynn E. TI The 3rd Schizophrenia International Research Society Conference, 14-18 April 2012, Florence, Italy: Summaries of oral sessions SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Genetics; Gene-environment interaction; Brain imaging; Treatment; Conference ID COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; PSYCHOTIC-LIKE EXPERIENCES; PLACEBO-CONTROLLED-TRIAL; BIPOLAR DISORDER; DOPAMINE RELEASE; 1ST-EPISODE SCHIZOPHRENIA; PATERNAL AGE; DOUBLE-BLIND; CANNABIS USE AB The 3rd Schizophrenia International Research Society Conference was held in Florence, Italy, April 14-18, 2012 and this year had as its emphasis, "The Globalization of Research". Student travel awardees served as rapporteurs for each oral session and focused their summaries on the most significant findings that emerged and the discussions that followed. The following report is a composite of these summaries. We hope that it will provide an overview for those who were present, but could not participate in all sessions, and those who did not have the opportunity to attend, but who would be interested in an update on current investigations ongoing in the field of schizophrenia research. (C) 2012 Elsevier B.V. All rights reserved. C1 [Quan, Meina; DeLisi, Lynn E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Lab Neurosci,Dept Psychiat, Brockton, MA 02301 USA. [Quan, Meina] Harvard Univ, Sch Med, Brigham & Womens Hosp, Psychiat Neuroimaging Lab,Dept Psychiat, Boston, MA 02215 USA. [Rubio, Maria D.] Univ Alabama Birmingham, Dept Psychiat & Behav Neurobiol, Birmingham, AL 35233 USA. [de Azua, Sonia Ruiz] Univ Basque Country, Univ Hosp Alava, CIBERSAM Biomed Res Ctr Mental Hlth Net, Vitoria 01004, Spain. [Sahoo, Saddichha] Univ British Columbia, Dept Psychiat, Vancouver, BC V6T 1Z3, Canada. [Strauss, Gregory P.] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. [Szczepankiewicz, Aleksandra] Poznan Univ Med Sci, Dept Psychiat Genet, Lab Mol & Cell Biol, PL-60572 Poznan, Poland. [Thompson, Andrew D.] Orygen Youth Hlth Res Ctr, Parkville, Vic 3052, Australia. [Trotta, Antonella] Kings Coll London, Inst Psychiat, London, England. [Tully, Laura M.] Harvard Univ, Cambridge, MA 02138 USA. [Uchida, Hiroyuki] Keio Univ, Sch Med, Dept Neuropsychiat, Shinjuku Ku, Tokyo 1608582, Japan. [Velthorst, Eva] Univ Amsterdam, Acad Med Ctr, Dept Early Psychosis, NL-1105 AZ Amsterdam, Netherlands. [Young, Jared W.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Abbs, Brandon] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Connors Ctr Womens Hlth,Dept Psychiat, Boston, MA 02120 USA. [Abbs, Brandon] Govt Med Coll, Dept Psychiat, Aurangabad, Maharashtra, India. [Adelufosi, Adegoke O.] Ladoke Akintola Univ, Teaching Hosp LAUTECH, Dept Psychiat, Ogbomosho, Oyo State, Nigeria. [Aktener, Ahmet Yigit] Goksun State Hosp, Goksun, Kahramanmaras, Turkey. [Beveridge, Natalie J.] Univ Newcastle, Schizophrenia Res Inst, Sch Biomed Sci & Pharm, Callaghan, NSW 2308, Australia. [Bhakta, Savita G.] Zucker Hillside Hosp, Hofstra NSLIJHS Sch Med, Glen Oaks, NY 11004 USA. [Blackman, Rachael K.] Univ Minnesota, Dept Neurosci, Minneapolis, MN USA. [Blackman, Rachael K.] Brain Sci Ctr VA Med Ctr, Minneapolis, MN USA. [Bora, Emre] Melbourne Hlth, Melbourne, Vic, Australia. [Bora, Emre] Univ Melbourne, Dept Psychiat, Melbourne Neuropsychiat Ctr, Melbourne, Vic 3010, Australia. [Byun, M. S.] Seoul Natl Univ, Coll Med, Dept Psychiat, Seoul, South Korea. [Cabanis, Maurice] Univ Marburg, Dept Psychiat & Psychotherapy, D-35039 Marburg, Germany. [Carrion, Ricardo] NS LIJHS, Zucker Hillside Hosp, Div Psychiat Res, Glen Oaks, NY USA. [Carrion, Ricardo] N Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Ctr Psychiat Neurosci, Manhasset, NY 11030 USA. [Castellani, Christina A.] Univ Western Ontario, Dept Biol, Mol Genet Unit, London, ON, Canada. [Chow, Tze Jen] Univ Tunku Abdul Rahman, Kuala Lumpur 53300, Malaysia. [Dmitrzak-Weglarz, M.] Poznan Univ Med Sci, Dept Psychiat, Psychiat Genet Unit, PL-60572 Poznan, Poland. [Gayer-Anderson, Charlotte] Kings Coll London, Inst Psychiat, London SE5 8AF, England. [Gomes, Felipe V.] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, BR-14049900 Ribeirao Preto, SP, Brazil. [Haut, Kristen] Univ Calif Los Angeles, Los Angeles, CA 90095 USA. [Hori, Hiroaki] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Mental Disorder Res, Kodaira, Tokyo 1878502, Japan. [Kantrowitz, Joshua T.] Nathan S Kline Inst Psychiat Res, New York State Psychiat Inst, New York, NY 10023 USA. [Kishimoto, Taishiro] Zucker Hillside Hosp, Glen Oaks, NY 11004 USA. [Kishimoto, Taishiro] Keio Univ, Sch Med, Shinjuku Ku, Tokyo, Japan. [Lee, Frankie H. F.] Ctr Addict & Mental Hlth, Toronto, ON M5T 1R8, Canada. [Lee, Frankie H. F.] Univ Toronto, Dept Pharmacol, Toronto, ON M5S 1A8, Canada. [Lin, Ashleigh] Univ Birmingham, Sch Psychol, Edgbaston B15 2TT, England. [Palaniyappan, Lena] Univ Nottingham, Inst Mental Hlth, Div Psychiat, Nottingham NG7 2TU, England. RP DeLisi, LE (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Lab Neurosci,Dept Psychiat, 940 Belmont St, Brockton, MA 02301 USA. EM babbs@partners.org; rashminachalia@gmail.com; ozotee@gmail.com; ahmet.aktener@deu.edu.tr; natalie.beveridge@newcastle.edu.au; sbhakta@nshs.edu; black343@umn.edu; ibora@unimelb.edu.au; bminsoo@gmail.com; cabanis@med.uni-marburg.de; RCarrion@NSHS.edu; ccastel3@uwo.ca; tzejenchow@yahoo.co.uk; mweglarz@ump.edu.pl; charlotte.gayer-anderson@kcl.ac.uk; gomesfv@usp.br; haut005@umn.edu; hori@ncnp.go.jp; jk3380@columbia.edu; taishiro-k@mti.biglobe.ne.jp; frankie.lee@utoronto.ca; a.lin@bham.ac.uk; Lena.Palaniyappan@nottingham.ac.uk; meina@bwh.harvard.edu; mrubio@uab.edu; sonia.ruizdeazuagarcia@osakidetza.net; saddichha@gmail.com; gstrauss@mprc.umaryland.edu; alszczep@gmail.com; andyt@unimelb.edu.au; antonella.a.trotta@kcl.ac.uk; ltully@fas.harvard.edu; mcn41320@biglobe.ne.jp; e.velthorst@amc.uva.nl; jaredyoung@ucsd.edu; anne_o'shea@hms.harvard.edu; DeLisi76@aol.com RI Young, Jared/G-9601-2012; Gomes, Felipe/C-3151-2013; Palaniyappan, Lena/L-8911-2016; Thompson, Andrew/F-3153-2012; bora, emre/D-4123-2009; Uchida, Hiroyuki/I-4867-2015; Sahoo, Saddichha/K-8380-2015 OI Trotta, Antonella/0000-0001-7538-6145; Tully, Laura/0000-0002-2751-9887; RUIZ DE AZUA GARCIA, SONIA/0000-0002-9876-2526; Palaniyappan, Lena/0000-0003-1640-7182; Castellani, Christina/0000-0003-2737-0549; bora, emre/0000-0002-1598-6832; Achalia, Rashmin/0000-0003-3822-4379; Carrion, Ricardo/0000-0002-6393-392X; Thompson, Andrew/0000-0002-0567-6013; Uchida, Hiroyuki/0000-0002-0628-7036; Sahoo, Saddichha/0000-0001-7351-6313 FU NIMH [MHR13MH082446] FX The early investigator program was funded by NIMH (MHR13MH082446). The information in these reports and the accuracy of each statement were the sole responsibility of each rapporteur and is based on personal interpretations of what was heard. Where possible speakers from all sessions were contacted by the rapporteurs to verify statements made. Please note that the speakers' professorial status was not indicated as they varied from Professor, to Doctor, to trainee. NR 163 TC 5 Z9 5 U1 8 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 2012 VL 141 IS 1 BP E1 EP E24 DI 10.1016/j.schres.2012.07.024 PG 24 WC Psychiatry SC Psychiatry GA 004VK UT WOS:000308709100001 PM 22910407 ER PT J AU Yagi, M Sobel, M AF Yagi, Mayumi Sobel, Michael TI Response to: Heparin and platelet activation, Jagroop-Dearing & Mikhailidis SO THROMBOSIS RESEARCH LA English DT Letter C1 [Yagi, Mayumi; Sobel, Michael] VA Puget Sound HCS, Seattle, WA 98108 USA. RP Yagi, M (reprint author), VA Puget Sound HCS, 1660 S Columbian Way, Seattle, WA 98108 USA. EM myagi@uw.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD OCT PY 2012 VL 130 IS 4 BP 686 EP 686 DI 10.1016/j.thromres.2012.07.015 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 007WQ UT WOS:000308919500031 ER PT J AU Bogoch, II Andrews, JR Ephraim, RK Utzinger, J AF Bogoch, Isaac I. Andrews, Jason R. Dadzie Ephraim, Richard K. Utzinger, Juerg TI Simple questionnaire and urine reagent strips compared to microscopy for the diagnosis of Schistosoma haematobium in a community in northern Ghana SO TROPICAL MEDICINE & INTERNATIONAL HEALTH LA English DT Article DE schistosomiasis; Schistosoma haematobium; diagnosis; questionnaire; urine reagent strip; microscopy; Ghana; schistosomiase; Schistosoma haematobium; diagnostic; questionnaire; bandelette reactive urinaire; microscopie; Ghana; esquistosomiasis; Schistosoma haematobium; diagnostico; cuestionario; tira reactiva de orina; microscopia; Ghana ID NEGLECTED TROPICAL DISEASES; SUB-SAHARAN AFRICA; UPPER EAST REGION; HEMATOBIUM INFECTION; SCHOOL-CHILDREN; REPORTED BLOOD; HEMATURIA; PERFORMANCE; PREVALENCE; INDICATORS AB Objectives To evaluate the utility of a simple questionnaire and urine reagent strip testing for the rapid diagnosis of Schistosoma haematobium in rural northern Ghana. Methods Cross-sectional parasitological and questionnaire survey in a community in northern Ghana. Participants provided two urine specimens that were examined under a microscope using a centrifugation method. The first urine sample was additionally subjected to reagent strip testing. A short questionnaire was administered to all participants. Results Microscopy of urine samples obtained from 208 individuals aged 177 years revealed an S. haematobium prevalence of 6.8%. The presence of any blood or protein on a urine reagent strip was 100% and 42% sensitive, and 93% and 80% specific for S. haematobium diagnosis. Questionnaires were completed by 198 individuals. Self-reported haematuria showed a sensitivity of 53% and a specificity of 85%. A dichotomous two-question panel was helpful in S. haematobium diagnosis, with working and playing near the river significantly associated with S. haematobium infection (P < 0.001). Conclusion The use of urine reagent strips, coupled with questions pertaining to water contact patterns, might be considered for point-of-contact diagnosis of S. haematobium where microscopy is unavailable. C1 [Bogoch, Isaac I.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Bogoch, Isaac I.] Univ Hlth Network, Div Infect Dis, Trop Med Unit, Toronto, ON, Canada. [Bogoch, Isaac I.] Univ Hlth Network, Div Gen Internal Med, Toronto, ON, Canada. [Bogoch, Isaac I.; Andrews, Jason R.] Harvard Univ, Sch Med, Boston, MA USA. [Dadzie Ephraim, Richard K.] Tamale Teaching Hosp, Div Lab Med, Tamale, Ghana. [Utzinger, Juerg] Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland. [Utzinger, Juerg] Univ Basel, Basel, Switzerland. RP Bogoch, II (reprint author), Massachusetts Gen Hosp, Div Infect Dis, COX 5,55 Fruit St, Boston, MA 02114 USA. EM isaac.bogoch@utoronto.ca OI Andrews, Jason/0000-0002-5967-251X NR 26 TC 13 Z9 14 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1360-2276 J9 TROP MED INT HEALTH JI Trop. Med. Int. Health PD OCT PY 2012 VL 17 IS 10 BP 1217 EP 1221 DI 10.1111/j.1365-3156.2012.03054.x PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 004XG UT WOS:000308714200007 PM 22863035 ER PT J AU Reish, RG Damjanovic, B Colwell, AS AF Reish, Richard G. Damjanovic, Branimir Colwell, Amy S. TI Deep Venous Thrombosis Prophylaxis in Body Contouring 105 Consecutive Patients SO ANNALS OF PLASTIC SURGERY LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the Northeastern-Society-of-Plastic-Surgeons (NESPS) CY OCT 20-23, 2011 CL Amelia Island, FL SP NE Soc Plast Surg (NESPS) DE body contouring; abdominoplasty; venous thromboembolism; DVT; PE; prophylaxis; prevention; plastic surgery ID PLASTIC-SURGERY PATIENTS; THROMBOEMBOLISM; PREVENTION; REDUCTION; EFFICACY AB Body contouring has a higher rate of thromboembolism than traditional plastic surgery procedures. Although risk stratification protocols exist, few offer specific therapeutic guidelines for deep venous thrombosis prevention. This single surgeon series classifies 105 consecutive patients into low, moderate, high, and highest risk groups. The respective thromboembolism prevention treatment included pneumatic compression devices alone, postoperative low-dose unfractionated heparin (LDUH), preoperative and 2 doses of postoperative LDUH, and preoperative and postoperative LDUH/low-dose molecular weight heparin for 7 days. Complications included 1 reoperation for bleeding. There were no clinically detected deep venous thromboses. In conclusion, this treatment algorithm for thromboembolism prevention results in a low rate of bleeding and thrombosis. Further studies are warranted to determine optimal timing and duration of chemoprophylaxis in plastic surgery patients. C1 [Reish, Richard G.; Damjanovic, Branimir; Colwell, Amy S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA 02114 USA. RP Colwell, AS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA 02114 USA. EM acolwell@partners.org NR 12 TC 8 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD OCT PY 2012 VL 69 IS 4 BP 412 EP 414 DI 10.1097/SAP.0b013e31824a45e0 PG 3 WC Surgery SC Surgery GA 007CN UT WOS:000308866500019 PM 22964679 ER PT J AU Craft, RO Damjanovic, B Colwell, AS AF Craft, Randall O. Damjanovic, Branimir Colwell, Amy S. TI Evidence-Based Protocol for Infection Control in Immediate Implant-Based Breast Reconstruction SO ANNALS OF PLASTIC SURGERY LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the Northeastern-Society-of-Plastic-Surgeons (NESPS) CY OCT 20-23, 2011 CL Amelia Island, FL SP NE Soc Plast Surg (NESPS) DE breast; infection; implant reconstruction ID SURGICAL-SITE INFECTIONS; STAPHYLOCOCCUS-AUREUS INFECTIONS; POVIDONE-IODINE IRRIGATION; INTRANASAL MUPIROCIN; PATIENT SATISFACTION; CAPSULAR CONTRACTURE; KNEE ARTHROPLASTY; POCKET IRRIGATION; NASAL CARRIAGE; COMPLICATIONS AB Immediate breast implant reconstruction has among the highest incidence of infections in plastic surgery. A literature search returned key articles that showed a significant decrease in surgical-site infections by performing nasal swab evaluation to treat methicillin-sensitive and methicillin-resistant Staphylococcus aureus before surgery with mupirocin nasal ointment and 5 days of chlorhexidine scrub to the surgical area. Additional Level 1 data supported the use of chlorhexidine-alcohol over povidone-iodine solutions for skin preparation. Intraoperative data on breast pocket irrigation showed the benefits of povidone-iodine as well as a triple antibiotic solution. Nasal swabs from 120 patients showed no methicillin-resistant S. aureus but did identify 10 patients with methicillin-sensitive S. aureus, 1 with streptococcus, and 3 with gram-negative rods, which changed perioperative antibiotic management. On the basis of the previously mentioned data, an evidence-based protocol for infection control was developed to potentially decrease infection rates. Further cost and efficacy data are warranted. C1 [Craft, Randall O.; Damjanovic, Branimir; Colwell, Amy S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA 02114 USA. RP Craft, RO (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA 02114 USA. EM rcraft@partners.org NR 36 TC 10 Z9 10 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD OCT PY 2012 VL 69 IS 4 BP 446 EP 450 DI 10.1097/SAP.0b013e31824a215a PG 5 WC Surgery SC Surgery GA 007CN UT WOS:000308866500029 PM 22964685 ER PT J AU Kirkham, JC Lee, JH Medina, MA McCormack, MC Randolph, MA Austen, WG AF Kirkham, John C. Lee, Jeffrey H. Medina, Miguel A., III McCormack, Michael C. Randolph, Mark A. Austen, William G., Jr. TI The Impact of Liposuction Cannula Size on Adipocyte Viability SO ANNALS OF PLASTIC SURGERY LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the Northeastern-Society-of-Plastic-Surgeons (NESPS) CY OCT 20-23, 2011 CL Amelia Island, FL SP NE Soc Plast Surg (NESPS) DE fat graft; fat transfer; autologous fat graft; autologous fat transfer; liposuction; nude mouse; animal model; adipocyte; adipose; histology ID ADIPOSE-TISSUE; FAT; CELLS; MODEL AB Purpose: Autologous fat transfer ("fat grafting") is widely used in cosmetic and reconstructive surgery, but long-term outcomes remain inconsistent. Each step in the transfer process can cause mechanical damage to the graft tissue. In particular, liposuction breaks aspirated adipose tissue into distinct globules and subjects it to shear forces, both of which can impact subsequent fat graft viability. The optimal size of the liposuction cannula for use in fat grafting is not known. Methods and Techniques: Controlled lipoaspirate samples were collected from adult female patients undergoing elective liposuction of the abdomen and flanks with uniform aspiration pressure (-25 in Hg) and either a 3- or 5-mm standard blunt-tip liposuction cannula. Individual grafts of 1.00 +/- (0.01) gram were prepared and injected into the bilateral flanks of nude mice with a 14-gauge catheter. After six weeks, these grafts were explanted and analyzed by weight and histology. Results: At six weeks, fat lobules in the 5-mm group retained 25% more weight than those in the 3-mm group [mean (SD), 0.70 (0.07) vs 0.56 (0.09) g, n = 24/group, P < 0.01). Histologic analysis revealed more intact, nucleated adipocytes in the 5-mm group than in the 3-mm group [4.42 (0.92) vs 3.10 (0.56) on a 1-5 rating scale]. The 5-mm group exhibited both less infiltrate [1.58 (0.17) vs 3.13 (0.70)] and less fibrosis [1.67 (0.45) vs 3.13 (0.89)] than the 3-mm group. Conclusions: In this controlled model of fat grafting with either a 5- or 3-mm aspiration cannula, the use of a larger aspiration cannula led to improved graft retention and quality. This finding has important implications for clinical applications of fat grafting. C1 [Kirkham, John C.; Lee, Jeffrey H.; Medina, Miguel A., III; McCormack, Michael C.; Randolph, Mark A.; Austen, William G., Jr.] Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. RP Kirkham, JC (reprint author), Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, 15 Parkman St, Boston, MA 02114 USA. EM jkirkham@partners.org NR 9 TC 17 Z9 17 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD OCT PY 2012 VL 69 IS 4 BP 479 EP 481 DI 10.1097/SAP.0b013e31824a459f PG 3 WC Surgery SC Surgery GA 007CN UT WOS:000308866500036 PM 22964677 ER PT J AU Fox, MD Buckner, RL White, MP Greicius, MD Pascual-Leone, A AF Fox, Michael D. Buckner, Randy L. White, Matthew P. Greicius, Michael D. Pascual-Leone, Alvaro TI Efficacy of Transcranial Magnetic Stimulation Targets for Depression Is Related to Intrinsic Functional Connectivity with the Subgenual Cingulate SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Depression; dorsolateral prefrontal cortex; intrinsic connectivity; MRI; resting state functional connectivity; subgenual; TMS; transcranial magnetic stimulation ID DORSOLATERAL PREFRONTAL CORTEX; TREATMENT-RESISTANT DEPRESSION; CEREBRAL-BLOOD-FLOW; GLOBAL SIGNAL REGRESSION; DEEP BRAIN-STIMULATION; ANTERIOR CINGULATE; MAJOR DEPRESSION; PARIETAL CORTEX; GLUCOSE-METABOLISM; CLINICAL-RESPONSE AB Background: Transcranial magnetic stimulation (TMS) to the left dorsolateral prefrontal cortex (DLPFC) is used clinically for the treatment of depression. However, the antidepressant mechanism remains unknown and its therapeutic efficacy remains limited. Recent data suggest that some left DLPFC targets are more effective than others; however, the reasons for this heterogeneity and how to capitalize on this information remain unclear. Methods: Intrinsic (resting state) functional magnetic resonance imaging data from 98 normal subjects were used to compute functional connectivity with various left DLPFC TMS targets employed in the literature. Differences in functional connectivity related to differences in previously reported clinical efficacy were identified. This information was translated into a connectivity-based targeting strategy to identify optimized left DLPFC TMS coordinates. Results in normal subjects were tested for reproducibility in an independent cohort of 13 patients with depression. Results: Differences in functional connectivity were related to previously reported differences in clinical efficacy across a distributed set of cortical and limbic regions. Dorsolateral prefrontal cortex TMS sites with better clinical efficacy were more negatively correlated (anticorrelated) with the subgenual cingulate. Optimum connectivity-based stimulation coordinates were identified in Brodmann area 46. Results were reproducible in patients with depression. Conclusions: Reported antidepressant efficacy of different left DLPFC TMS sites is related to the anticorrelation of each site with the subgenual cingulate, potentially lending insight into the antidepressant mechanism of TMS and suggesting a role for intrinsically anticorrelated networks in depression. These results can be translated into a connectivity-based targeting strategy for focal brain stimulation that might be used to optimize clinical response. C1 [Fox, Michael D.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fox, Michael D.; Pascual-Leone, Alvaro] Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Boston, MA 02215 USA. [Fox, Michael D.; Buckner, Randy L.] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Buckner, Randy L.] Harvard Univ, Dept Psychol, Ctr Brain Sci, Cambridge, MA 02138 USA. [White, Matthew P.] Stanford Univ, Dept Psychiat & Behav Sci, Sch Med, Stanford, CA 94305 USA. [Greicius, Michael D.] Stanford Univ, Dept Neurol & Neurol Sci, Sch Med, Funct Imaging Neuropsychiat Disorders Lab, Stanford, CA 94305 USA. [Pascual-Leone, Alvaro] Univ Autonoma Barcelona, Inst Guttmann, Inst Univ, Hosp Neurorehabil, E-08193 Barcelona, Spain. RP Fox, MD (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Massachusetts Gen Hosp, WACC 8-835,55 Fruit St, Boston, MA 02114 USA. EM foxmdphd@gmail.com FU National Institutes of Health [R25NS065743]; National Center for Research Resources: Harvard Clinical and Translational Science Center [UL1 RR025758]; Howard Hughes Medical Institute; Dana Foundation FX MDF was supported by National Institutes of Health Grant R25NS065743. Work on this study was also supported by grants from the National Institutes of Health and National Center for Research Resources: Harvard Clinical and Translational Science Center (UL1 RR025758), the Howard Hughes Medical Institute, and the Dana Foundation. NR 73 TC 116 Z9 119 U1 3 U2 25 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 1 PY 2012 VL 72 IS 7 BP 595 EP 603 DI 10.1016/j.biopsych.2012.04.028 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 004XE UT WOS:000308714000014 PM 22658708 ER PT J AU Saeidi, N Karmelek, KP Paten, JA Zareian, R DiMasi, E Ruberti, JW AF Saeidi, Nima Karmelek, Kathryn P. Paten, Jeffrey A. Zareian, Ramin DiMasi, Elaine Ruberti, Jeffrey W. TI Molecular crowding of collagen: A pathway to produce highly-organized collagenous structures SO BIOMATERIALS LA English DT Article DE Collagen; Molecular crowding; Extracellular matrix; Organized matrix; Corneal tissue engineering ID LUMICAN-NULL MICE; CORNEAL STROMA; EXTRACELLULAR-MATRIX; INTERVERTEBRAL DISC; CELL LOCOMOTION; HYALURONIC-ACID; TENDON; FIBRIL; MORPHOGENESIS; FIBROBLASTS AB Collagen in vertebrate animals is often arranged in alternating lamellae or in bundles of aligned fibrils which are designed to withstand in vivo mechanical loads. The formation of these organized structures is thought to result from a complex, large-area integration of individual cell motion and locally-controlled synthesis of fibrillar arrays via cell-surface fibripositors (direct matrix printing). The difficulty of reproducing such a process in vitro has prevented tissue engineers from constructing clinically useful load-bearing connective tissue directly from collagen. However, we and others have taken the view that long-range organizational information is potentially encoded into the structure of the collagen molecule itself, allowing the control of fibril organization to extend far from cell (or bounding) surfaces. We here demonstrate a simple, fast, cell-free method capable of producing highly-organized, anistropic collagen fibrillar lamellae de novo which persist over relatively long-distances (tens to hundreds of microns). Our approach to nanoscale organizational control takes advantage of the intrinsic physiochemical properties of collagen molecules by inducing collagen association through molecular crowding and geometric confinement. To mimic biological tissues which comprise planar, aligned collagen lamellae (e.g. cornea, lamellar bone or annulus fibrosus), type I collagen was confined to a thin, planar geometry, concentrated through molecular crowding and polymerized. The resulting fibrillar lamellae show a striking resemblance to native load-bearing lamellae in that the fibrils are small, generally aligned in the plane of the confining space and change direction en masse throughout the thickness of the construct. The process of organizational control is consistent with embryonic development where the bounded planar cell sheets produced by fibroblasts suggest a similar confinement/concentration strategy. Such a simple approach to nanoscale organizational control of structure not only makes de novo tissue engineering a possibility, but also suggests a clearer pathway to organization for fibroblasts than direct matrix printing. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Karmelek, Kathryn P.; Paten, Jeffrey A.; Zareian, Ramin; Ruberti, Jeffrey W.] Northeastern Univ, Dept Mech & Ind Engn, Boston, MA 02115 USA. [Saeidi, Nima] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. [DiMasi, Elaine] Brookhaven Natl Lab, Photon Sci Div, Upton, NY 11973 USA. RP Ruberti, JW (reprint author), Northeastern Univ, Dept Mech & Ind Engn, 360 Huntington Ave,334 Snell Engn, Boston, MA 02115 USA. EM nsaeidi@partners.org; kkarmelek@gmail.com; patenaude.je@neu.edu; zareian.r@neu.edu; dimasi@bnl.gov; j.ruberti@neu.edu FU NIH/NEI [1R01 EY015500-01]; USDOE [DE-AC02-98CH10886] FX This investigation was supported by NIH/NEI 1R01 EY015500-01. Work performed at Brookhaven National Laboratory is supported under USDOE Contract DE-AC02-98CH10886. The authors would like to thank Dr. Ahmed Busnaina and Dr. Sivasubramanian Samu from Center for High-rate Nanomanufacturing, Northeastern University for providing the SWNTs and assisting with the imaging. NR 66 TC 29 Z9 31 U1 1 U2 57 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD OCT PY 2012 VL 33 IS 30 BP 7366 EP 7374 DI 10.1016/j.biomaterials.2012.06.041 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 002HZ UT WOS:000308524000006 PM 22846420 ER PT J AU Kong, WH Sung, DK Kim, KS Jung, HS Gho, EJ Yun, SH Hahn, SK AF Kong, Won Ho Sung, Dong Kyung Kim, Ki Su Jung, Ho Sang Gho, Eun Ji Yun, Seok Hyun Hahn, Sei Kwang TI Self-assembled complex of probe peptide - E. Coli RNA I conjugate and nano graphene oxide for apoptosis diagnosis SO BIOMATERIALS LA English DT Article DE Graphene oxide; Caspase; pi-pi stacking; Apoptosis; Diagnosis ID RESONANCE ENERGY-TRANSFER; LIVE CELLS; CASPASE-3 ACTIVATION; REAL-TIME; DNA; ISCHEMIA AB Caspase-3 plays an important role in the initiation and propagation of apoptosis which is involved in various kinds of diseases including neurodegenerative diseases and inflammatory diseases. The capase-3 cleavable site of Asp-Glu-Val-Asp (DEVD) connected to a partial sequence of Escherichia coli RNAI was labeled with tetramethyl-6-carboxyrhodamine (TAMRA) as an optical probe. Graphene oxide (GO) was synthesized by a modified Hummer's method and exploited for the preparation of nano-sized GO (NGO) conjugated with polyethylene glycol (PEG). After binding the NGO-PEG by pi-pi stacking, the quenched fluorescence of TAMRA-DEVD-single stranded DNA (ssDNA) conjugate was recovered via the enzymatic cleavage by caspase-3 in live A549 cells. The comparative study with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay clearly confirmed the specific detection of apoptosis by the non-covalent TAMRA-DEVD-ssDNA/NGO-PEG complex. Furthermore, the self-assembled NGO complex was successfully exploited for in vivo diagnosis of apoptosis-related diseases like hypoxic-ischemic encephalopathy (HIE) and liver cirrhosis. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Kong, Won Ho; Kim, Ki Su; Jung, Ho Sang; Gho, Eun Ji; Hahn, Sei Kwang] Pohang Univ Sci & Technol POSTECH, Dept Mat Sci & Engn, Pohang 790784, Kyungbuk, South Korea. [Sung, Dong Kyung] Samsung Biomed Res Inst, Seoul 135710, South Korea. [Yun, Seok Hyun; Hahn, Sei Kwang] Harvard Univ, Sch Med, Wellman Ctr Photomed, Cambridge, MA 02139 USA. [Yun, Seok Hyun; Hahn, Sei Kwang] Massachusetts Gen Hosp, Cambridge, MA 02139 USA. RP Hahn, SK (reprint author), Pohang Univ Sci & Technol POSTECH, Dept Mat Sci & Engn, San 31 Hyoja Dong, Pohang 790784, Kyungbuk, South Korea. EM skhanb@postech.ac.kr FU Converging Research Center Program through the National Research Foundation of Korea (NRF); Ministry of Education, Science and Technology [2009-0081871]; POSCO [4.0007652.09]; NRF; MEST [2009-0084578] FX This work was financially supported by the Converging Research Center Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0081871). This work was also financially supported by POSCO (#4.0007652.09). This study was also supported by Mid-career Researcher Program through NRF grant funded by the MEST (No. 2009-0084578). NR 29 TC 10 Z9 10 U1 3 U2 86 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 EI 1878-5905 J9 BIOMATERIALS JI Biomaterials PD OCT PY 2012 VL 33 IS 30 BP 7556 EP 7564 DI 10.1016/j.biomaterials.2012.06.086 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 002HZ UT WOS:000308524000025 PM 22818651 ER PT J AU Ackerman, KE Putman, M Guereca, G Taylor, AP Pierce, L Herzog, DB Klibanski, A Bouxsein, M Misra, M AF Ackerman, Kathryn E. Putman, Melissa Guereca, Gabriela Taylor, Alexander P. Pierce, Lisa Herzog, David B. Klibanski, Anne Bouxsein, Mary Misra, Madhusmita TI Cortical microstructure and estimated bone strength in young amenorrheic athletes, eumenorrheic athletes and non-athletes SO BONE LA English DT Article DE Athletes; Adolescents; Bone strength; Stiffness; Failure load ID QUANTITATIVE COMPUTED-TOMOGRAPHY; FINITE-ELEMENT-ANALYSIS; TRABECULAR STRUCTURE-ANALYSIS; INDUCED FLUID-FLOW; PANEL VOLUME CT; VIVO HR-PQCT; DISTAL RADIUS; POSTMENOPAUSAL WOMEN; ADOLESCENT GIRLS; MINERAL DENSITY AB Context: Lower bone density in young amenorrheic athletes (AA) compared to eumenorrheic athletes (EA) and non-athletes may increase fracture risk during a critical time of bone accrual. Finite element analysis (FEA) is a unique tool to estimate bone strength in vivo, and the contribution of cortical microstructure to bone strength in young athletes is not well understood. Objective: We hypothesized that FEA-estimated stiffness and failure load are impaired in AA at the distal radius and tibia compared to EA and non-athletes despite weight-bearing exercise. Design and setting: Cross-sectional study; Clinical Research Center Subjects: 34 female endurance athletes involved in weight-bearing sports (17 AA, 17 EA) and 16 non-athletes (14-21 years) of comparable age, maturity and BMI Outcome measures: We used HR-pQCT images to assess cortical microarchitecture and FEA to estimate bone stiffness and failure load. Results: Cortical perimeter, porosity and trabecular area at the weight-bearing tibia were greater in both groups of athletes than non-athletes, whereas the ratio (%) of cortical to total area was lowest in AA. Despite greater cortical porosity in EA, estimated tibial stiffness and failure load was higher than in non-athletes. However, this advantage was lost in AA. At the non-weight-bearing radius, failure load and stiffness were lower in AA than non-athletes. After controlling for lean mass and menarchal age, athletic status accounted for 5-9% of the variability in stiffness and failure load, menarchal age for 8-23%, and lean mass for 12-37%. Conclusion: AA have lower FEA-estimated bone strength at the distal radius than non-athletes, and lose the advantage of weight-bearing exercise seen in EA at the distal tibia. (C) 2012 Elsevier Inc. All rights reserved. C1 [Ackerman, Kathryn E.; Guereca, Gabriela; Pierce, Lisa; Klibanski, Anne; Misra, Madhusmita] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Ackerman, Kathryn E.] Boston Childrens Hosp, Div Sports Med, Boston, MA 02115 USA. [Putman, Melissa; Taylor, Alexander P.; Bouxsein, Mary] Massachusetts Gen Hosp, Div Endocrine, Boston, MA 02114 USA. [Herzog, David B.] Massachusetts Gen Hosp, Harris Ctr, Boston, MA 02114 USA. [Misra, Madhusmita] Mass Gen Hosp Children, Pediat Endocrine Unit, Boston, MA 02114 USA. [Ackerman, Kathryn E.; Putman, Melissa; Guereca, Gabriela; Taylor, Alexander P.; Pierce, Lisa; Herzog, David B.; Klibanski, Anne; Bouxsein, Mary; Misra, Madhusmita] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Ackerman, KE (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457B,55 Fruit St, Boston, MA 02114 USA. EM keackerman@partners.org FU NCRR NIH HHS [S10 RR 023405, 1 UL1 RR025758-01, UL1 RR025758]; NICHD NIH HHS [1 R01 HD060827-01A1, R01 HD060827]; NIDDK NIH HHS [T32 DK007529, P30 DK040561] NR 51 TC 19 Z9 19 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD OCT PY 2012 VL 51 IS 4 BP 680 EP 687 DI 10.1016/j.bone.2012.07.019 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 005DH UT WOS:000308730200007 PM 22878154 ER PT J AU Verhoeven, JS Rommel, N Prodi, E Leemans, A Zink, I Vandewalle, E Noens, I Wagemans, J Steyaert, J Boets, B de Winckel, AV De Cock, P Lagae, L Sunaert, S AF Verhoeven, Judith S. Rommel, Nathalie Prodi, Elena Leemans, Alexander Zink, Inge Vandewalle, Ellen Noens, Ilse Wagemans, Johan Steyaert, Jean Boets, Bart de Winckel, Ann Van De Cock, Paul Lagae, Lieven Sunaert, Stefan TI Is There a Common Neuroanatomical Substrate of Language Deficit between Autism Spectrum Disorder and Specific Language Impairment? SO CEREBRAL CORTEX LA English DT Article DE autism spectrum disorder; diffusion tensor imaging; specific language impairment; superior longitudinal fascicle ID WHITE-MATTER MATURATION; COMPARATIVE FOLLOW-UP; DIAGNOSTIC INTERVIEW; READING ABILITIES; INFANTILE-AUTISM; CHROMOSOME 7Q; HUMAN BRAIN; CHILDREN; CHILDHOOD; LINKAGE AB Discussion of an overlap between specific language impairment (SLI) and autism spectrum disorder (ASD) is on going. The most intriguing overlap between both phenotypes is the similarity in the observed language deficits described in SLI and a subgroup of ASD with co-occurring linguistic impairment, ASD-LI. Examining whether a similar neuroanatomical substrate underlies this phenotypical linguistic overlap, we studied the white matter microstructural properties of the superior longitudinal fascicle (SLF) of 19 ASD-LI adolescents (mean age 13.8 +/- 1.6 years) and 21 age-matched controls and compared them with 13 SLI children (mean age 10.1 +/- 0.4 years) and 12 age-matched controls. A linguistic profile assessment and a diffusion tensor imaging analysis of the SLF were performed. Linguistic testing revealed a mixed receptive-expressive disorder profile in both groups, confirming their overlap at phenotypical level. At neuroanatomical level, no significant differences in mean SLF fractional anisotropy (FA) and mean SLF apparent diffusion coefficient values between ASD-LI participants and controls were seen. By contrast, the mean SLF FA was significantly reduced in the SLI children as compared with their controls. The observation of structural SLF disturbances in SLI but not in ASD-LI suggests the existence of a different neuroanatomical substrate for the language deficits in both disorders. C1 [Verhoeven, Judith S.; Prodi, Elena; Sunaert, Stefan] Catholic Univ Louvain, Univ Hosp, Dept Radiol, B-3000 Louvain, Belgium. [Rommel, Nathalie; Zink, Inge; Vandewalle, Ellen] Catholic Univ Louvain, Univ Hosp, Dept Neurosci, Exp ORL, B-3000 Louvain, Belgium. [Verhoeven, Judith S.; Noens, Ilse; Wagemans, Johan; Steyaert, Jean; Boets, Bart; De Cock, Paul; Sunaert, Stefan] Catholic Univ Louvain, Leuven Autism Res Consortium, B-3000 Louvain, Belgium. [Verhoeven, Judith S.; De Cock, Paul; Lagae, Lieven] Catholic Univ Louvain, Univ Hosp, Dept Pediat, B-3000 Louvain, Belgium. [Prodi, Elena] Univ Milan, Dept Radiol, Ist Neurol Carlo Besta, Milan, Italy. [Leemans, Alexander] Univ Med Ctr Utrecht, Dept Radiol, Image Sci Inst, Utrecht, Netherlands. [Noens, Ilse; Boets, Bart] Univ Louvain, Dept Educ Sci, Parenting & Special Educ Res Grp, Louvain, Belgium. [Noens, Ilse] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Wagemans, Johan] Univ Louvain, Lab Expt Psychol, Louvain, Belgium. [Steyaert, Jean; Boets, Bart] Catholic Univ Louvain, Univ Hosp, Dept Child & Adolescent Psychiat, B-3000 Louvain, Belgium. [Steyaert, Jean] Univ Maastricht, Dept Clin Genet, Maastricht, Netherlands. [de Winckel, Ann Van] Catholic Univ Louvain, Univ Hosp, Ctr Dev Disabil, B-3000 Louvain, Belgium. [De Cock, Paul] Univ Louvain, Fac Kinesiol & Rehabil Sci, Dept Rehabil Sci, Louvain, Belgium. RP Sunaert, S (reprint author), Catholic Univ Louvain, Univ Hosp, Dept Radiol, Herestr 49, B-3000 Louvain, Belgium. EM Stefan.sunaert@uzleuven.be RI Leemans, Alexander/A-1784-2011; Rommel, Nathalie/D-6721-2014; Steyaert, Jean/B-5326-2015; OI Steyaert, Jean/0000-0003-2512-4694; Leemans, Alexander/0000-0002-9306-6126 FU Fund for Scientific Research-Flanders," FWO, Belgium [G.0354.06]; IUAP-KUL (FWO fellowship) [asp/07]; Research Council [IDO/08/013] FX "Fund for Scientific Research-Flanders," FWO, Belgium (G.0354.06); IUAP-KUL (FWO fellowship asp/07 to J.S.V.); the Research Council (IDO/08/013). NR 65 TC 30 Z9 30 U1 3 U2 37 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD OCT PY 2012 VL 22 IS 10 BP 2263 EP 2271 DI 10.1093/cercor/bhr292 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 002KI UT WOS:000308530500005 PM 22047968 ER PT J AU Tafti, BA Shaba, W Li, YX Yevdayev, E Berenji, GR AF Tafti, Bashir Akhavan Shaba, Wisam Li, Yuxin Yevdayev, Ella Berenji, Gholam Reza TI Staging and Follow-up of Lacrimal Gland Carcinomas by F-18-FDG PET/CT Imaging SO CLINICAL NUCLEAR MEDICINE LA English DT Editorial Material DE PET/CT; lacrimal gland; transitional cell carcinoma; tumor staging ID POSITRON-EMISSION-TOMOGRAPHY; NECK-CANCER; HEAD; MANAGEMENT; PATIENT; TUMORS C1 [Tafti, Bashir Akhavan; Shaba, Wisam; Li, Yuxin; Yevdayev, Ella; Berenji, Gholam Reza] Vet Adm Greater Los Angeles Hlth Care Syst, Dept Nucl Med, Los Angeles, CA 90073 USA. RP Berenji, GR (reprint author), Vet Adm Greater Los Angeles Hlth Care Syst, Dept Nucl Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM gholam.berenji@va.gov NR 13 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-9762 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD OCT PY 2012 VL 37 IS 10 BP E249 EP E252 DI 10.1097/RLU.0b013e31825ae11b PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 007BW UT WOS:000308864800003 PM 22899198 ER PT J AU Overs, S Hughes, CM Haselkorn, JK Turner, AP AF Overs, Shannon Hughes, Christina M. Haselkorn, Jodie K. Turner, Aaron P. TI Modifiable Comorbidities and Disability in Multiple Sclerosis SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Review DE Multiple sclerosis; Comorbid; Chronic illness; Hypertension; Diabetes; Obesity; Smoking; Clinical trials; Clinical care ID LIFE-STYLE FACTORS; CIGARETTE-SMOKING; COGNITIVE IMPAIRMENT; ORAL-CONTRACEPTIVES; DISEASE PROGRESSION; ALCOHOL-CONSUMPTION; INSULIN-RESISTANCE; CHRONIC ILLNESS; PRIMARY-CARE; RISK-FACTOR AB Multiple sclerosis is a common neurological disease that results in disability in early adulthood that may progress through a relatively normal lifespan. Other comorbid health conditions can increase the likelihood of progression of MS and independently contribute to limitations in activities and social participation. We examine common modifiable health conditions and behaviors, including hypertension, obesity, diabetes mellitus, alcohol, and smoking to determine their impacts on MS and disability. Appropriate identification and treatment can improve health status, diminish disability, and improve quality of life. C1 [Hughes, Christina M.; Haselkorn, Jodie K.; Turner, Aaron P.] VA Puget Sound Hlth Care Syst, Rehabil Care Serv, S RCS 117, Seattle, WA 98108 USA. [Overs, Shannon] Portland VA Med Ctr, Dept Neurol, Portland, OR 97239 USA. [Hughes, Christina M.; Haselkorn, Jodie K.; Turner, Aaron P.] Univ Washington, Dept Rehabil Med, Seattle, WA 98105 USA. [Haselkorn, Jodie K.] Univ Washington, Dept Epidemiol, Seattle, WA 98105 USA. RP Turner, AP (reprint author), VA Puget Sound Hlth Care Syst, Rehabil Care Serv, S RCS 117, 1660 S Columbian Way, Seattle, WA 98108 USA. EM Aaron.Turner@va.gov OI Turner, Aaron/0000-0001-6897-8003 NR 87 TC 7 Z9 8 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1528-4042 EI 1534-6293 J9 CURR NEUROL NEUROSCI JI Curr. Neurol. Neurosci. Rep. PD OCT PY 2012 VL 12 IS 5 BP 610 EP 617 DI 10.1007/s11910-012-0293-4 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 001DG UT WOS:000308439700014 PM 22791240 ER PT J AU Sayer, GT Baker, JN Parks, KA AF Sayer, Gabriel T. Baker, Joshua N. Parks, Kimberly A. TI Heart rescue: the role of mechanical circulatory support in the management of severe refractory cardiogenic shock SO CURRENT OPINION IN CRITICAL CARE LA English DT Review DE cardiogenic shock; mechanical circulatory support; percutaneous ventricular assist device; severe refractory shock ID VENTRICULAR ASSIST DEVICE; EXTRACORPOREAL MEMBRANE-OXYGENATION; ACUTE MYOCARDIAL-INFARCTION; OUTCOMES; TRIAL; BRIDGE; COUNTERPULSATION; EXPERIENCE; RECOVERY; SURVIVAL AB Purpose of review Cardiogenic shock is present in 3.5% of patients presenting with acute decompensated heart failure. Despite advances in therapy, mortality remains high, approaching 70% in some settings. Recent management strategies have incorporated the use of mechanical circulatory support (MCS), which has been associated with better survival in nonrandomized trials. MCS is increasingly used in the acute setting and has become an important treatment modality for cardiogenic shock. Recent findings Small studies have demonstrated improved survival when MCS is instituted early in the management of cardiogenic shock. Numerous case reports support the benefit of MCS for various causes of cardiogenic shock, including acute myocardial infarction, cardiac allograft rejection, myocarditis and refractory arrhythmias. Summary This article will review novel strategies in the management of cardiogenic shock including percutaneous MCS (intra-aortic balloon pump, Impella, TandemHeart, venoarterial extracorporeal membrane oxygenation) and surgically implanted devices (CentriMag) that are used for short-term management. We will review the mechanisms involved in cardiogenic shock and discuss management and device selection strategies. C1 [Sayer, Gabriel T.; Parks, Kimberly A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Adv Heart Failure Serv,Div Cardiol, Boston, MA 02114 USA. [Baker, Joshua N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mech Circulatory Support Serv,Div Cardiothorac Su, Boston, MA 02114 USA. RP Parks, KA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Adv Heart Failure Serv,Div Cardiol, 55 Fruit St,GB 800, Boston, MA 02114 USA. EM kaparks@partners.org FU Vortex Medical Inc.; Biotronik FX G.T S. has no disclosures. J.N.B. has received consulting fees from Vortex Medical Inc. K.A.P. has received consulting fees from Thoratec Inc. and speaking fees from Biotronik. NR 33 TC 16 Z9 19 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-5295 J9 CURR OPIN CRIT CARE JI Curr. Opin. Crit. Care PD OCT PY 2012 VL 18 IS 5 BP 409 EP 416 DI 10.1097/MCC.0b013e328357f1e6 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 004HF UT WOS:000308671400001 PM 22895213 ER PT J AU Greyson, CR AF Greyson, Clifford R. TI Right heart failure in the intensive care unit SO CURRENT OPINION IN CRITICAL CARE LA English DT Review DE cor pulmonale; pulmonary hypertension; right ventricle; ventricular assist device ID RIGHT-VENTRICULAR FAILURE; PULMONARY ARTERIAL-HYPERTENSION; RESPIRATORY-DISTRESS-SYNDROME; JUGULAR VENOUS DISTENSION; PRESSURE-OVERLOAD; ASSIST DEVICE; ATRIAL SEPTOSTOMY; SYSTOLIC FUNCTION; DYSFUNCTION; FLOW AB Purpose of review This review summarizes the approach to and recent developments in the evaluation and treatment of acute right heart failure in the ICU. Right heart failure, defined as failure of the right ventricle to provide sufficient blood flow through the pulmonary circulation at normal central venous pressure, is a common problem caused by a combination of increased right-ventricular afterload and right-ventricular contractile dysfunction. Recent findings Management of acute right heart failure continues to be challenging because of insufficient understanding of its pathophysiology, a lack of guidelines, and few available tools. Recent research has contributed to an improved understanding of its mechanisms, helping to guide therapy and suggest future options. Right-ventricular assist devices are emerging as a promising approach to treatment when optimization of hemodynamics and conventional medical therapy fail. Summary Right heart failure causes venous congestion and systemic hypoperfusion. Once right heart failure is identified, the primary goal is to alleviate any reversible cause of excessive load or right-ventricular contractile failure. When the underlying abnormalities cannot be alleviated, trials of diuretic, vasodilator, or inotropic therapy may be required. Invasive monitoring helps guide therapy. Medically refractory right heart failure may potentially be treated with right-ventricular assist devices. C1 [Greyson, Clifford R.] Dept Vet Affairs Med Ctr, Denver, CO USA. [Greyson, Clifford R.] Univ Colorado, Sch Med, Denver, CO USA. RP Greyson, CR (reprint author), Denver VAMC, 1055 Clermont St, Denver, CO 80220 USA. EM Clifford.Greyson@UCDenver.edu FU Department of Veterans Affairs Medical Research Service FX Supported by the Department of Veterans Affairs Medical Research Service. NR 46 TC 6 Z9 7 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-5295 J9 CURR OPIN CRIT CARE JI Curr. Opin. Crit. Care PD OCT PY 2012 VL 18 IS 5 BP 424 EP 431 DI 10.1097/MCC.0b013e3283577070 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 004HF UT WOS:000308671400003 PM 22889868 ER PT J AU Bartzokis, G Lu, P Couvrette, A Raven, E DeTore, N Altshuler, L Mintz, J Ventura, J Casaus, L Luo, J Subotnik, K Nuechterlein, K AF Bartzokis, George Lu, Po Couvrette, Alexander Raven, Erika DeTore, Nicole Altshuler, Lori Mintz, Jim Ventura, Joseph Casaus, Laurie Luo, John Subotnik, Kenneth Nuechterlein, Keith TI The mechanism of action of antipsychotics and intracortical myelination in schizophrenia SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Meeting Abstract C1 [Bartzokis, George; Lu, Po; Couvrette, Alexander; Raven, Erika; DeTore, Nicole; Altshuler, Lori; Ventura, Joseph; Casaus, Laurie; Luo, John; Subotnik, Kenneth; Nuechterlein, Keith] Univ Calif Los Angeles, Los Angeles, CA USA. [Bartzokis, George] Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. [Mintz, Jim] Univ Texas Hlth Sci Ctr, San Antonio, TX USA. RI Bartzokis, George/K-2409-2013; Mintz, Jim/N-7385-2014 OI Mintz, Jim/0000-0002-8299-5851 NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1751-7885 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD OCT PY 2012 VL 6 SU 1 SI SI BP 8 EP 8 PG 1 WC Psychiatry SC Psychiatry GA 003AI UT WOS:000308580100030 ER PT J AU Mathalon, DH AF Mathalon, Daniel H. CA NAPLS Consortium TI Neurophysiological abnormalities during processing of stimulus deviance in youth at clinical high risk for psychosis: an interim analysis of the NAPLS-2 data SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Meeting Abstract C1 [Mathalon, Daniel H.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Mathalon, Daniel H.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1751-7885 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD OCT PY 2012 VL 6 SU 1 SI SI BP 9 EP 9 PG 1 WC Psychiatry SC Psychiatry GA 003AI UT WOS:000308580100036 ER PT J AU Loewy, RL Pearson, R Schlosser, D Stuart, B Mathalon, D Vinogradov, S AF Loewy, Rachel L. Pearson, Rahel Schlosser, Danielle Stuart, Barbara Mathalon, Daniel Vinogradov, Sophia TI Childhood trauma, cortisol secretion and risk for psychosis SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Meeting Abstract C1 [Loewy, Rachel L.; Pearson, Rahel; Schlosser, Danielle; Stuart, Barbara; Mathalon, Daniel; Vinogradov, Sophia] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Mathalon, Daniel; Vinogradov, Sophia] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 3 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1751-7885 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD OCT PY 2012 VL 6 SU 1 SI SI BP 12 EP 12 PG 1 WC Psychiatry SC Psychiatry GA 003AI UT WOS:000308580100048 ER PT J AU Hill, M Crumlish, N Whitty, P Clarke, M Browne, S Gervin, M Macklin, E Kinsella, A Larkin, C Waddington, J O'Callaghan, E AF Hill, Michele Crumlish, Niall Whitty, Peter Clarke, Mary Browne, Stephen Gervin, Maurice Macklin, Eric Kinsella, Anthony Larkin, Conall Waddington, John O'Callaghan, Eadbhard TI Prospective relationship of duration of untreated psychosis to psychopathology and functional outcome over 12 years SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Meeting Abstract C1 [Hill, Michele; Macklin, Eric] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hill, Michele; Macklin, Eric] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RI Macklin, Eric/E-2955-2013 OI Macklin, Eric/0000-0003-1618-3502 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1751-7885 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD OCT PY 2012 VL 6 SU 1 SI SI BP 21 EP 21 PG 1 WC Psychiatry SC Psychiatry GA 003AI UT WOS:000308580100081 ER PT J AU Fulford, D Niendam, T Floyd, E Miskovich, T Carter, C Mathalon, D Vinogradov, S Loewy, R AF Fulford, Daniel Niendam, Tara Floyd, Erin Miskovich, Tara Carter, Cameron Mathalon, Daniel Vinogradov, Sophia Loewy, Rachel TI Symptom dimensions in early psychosis: examining the unique contributions of depression and anxiety on functional outcomes SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Meeting Abstract C1 [Fulford, Daniel; Mathalon, Daniel; Vinogradov, Sophia; Loewy, Rachel] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Niendam, Tara; Floyd, Erin; Miskovich, Tara; Carter, Cameron] Univ Calif Davis, Davis, CA 95616 USA. [Mathalon, Daniel; Vinogradov, Sophia] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1751-7885 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD OCT PY 2012 VL 6 SU 1 SI SI BP 33 EP 33 PG 1 WC Psychiatry SC Psychiatry GA 003AI UT WOS:000308580100121 ER PT J AU Seidman, LJ Goldstein, J Cherkerzian, S Agnew-Blais, J Tsuang, MT Buka, SL AF Seidman, Larry J. Goldstein, Jill Cherkerzian, Sara Agnew-Blais, Jessica Tsuang, Ming T. Buka, Stephen L. TI Was Kraepelin right? A 30-year follow-up of neurocognitive deterioration in schizophrenia versus bipolar psychosis SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Meeting Abstract C1 [Seidman, Larry J.; Goldstein, Jill; Tsuang, Ming T.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Cambridge, MA 02138 USA. [Seidman, Larry J.; Goldstein, Jill] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. [Goldstein, Jill; Cherkerzian, Sara] Brigham & Womens Hosp, Boston, MA 02115 USA. [Agnew-Blais, Jessica; Tsuang, Ming T.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Tsuang, Ming T.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Buka, Stephen L.] Brown Univ, Providence, RI 02912 USA. RI Buka, Stephen/H-7335-2014; Agnew-Blais, Jessica/L-9236-2015 OI Buka, Stephen/0000-0002-8578-9308; Agnew-Blais, Jessica/0000-0002-0755-6867 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1751-7885 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD OCT PY 2012 VL 6 SU 1 SI SI BP 33 EP 33 PG 1 WC Psychiatry SC Psychiatry GA 003AI UT WOS:000308580100124 ER PT J AU Yohannes, S Fulford, D Hardy, K Mathalon, D Vinogradov, S Loewy, R AF Yohannes, Seghel Fulford, Daniel Hardy, Kate Mathalon, Daniel Vinogradov, Sophia Loewy, Rachel TI Exploring the relationship between ethnicity and interviewer-rated symptom severity in early psychosis SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Meeting Abstract C1 [Yohannes, Seghel; Fulford, Daniel; Hardy, Kate; Mathalon, Daniel; Vinogradov, Sophia; Loewy, Rachel] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Fulford, Daniel; Vinogradov, Sophia] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1751-7885 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD OCT PY 2012 VL 6 SU 1 SI SI BP 81 EP 81 PG 1 WC Psychiatry SC Psychiatry GA 003AI UT WOS:000308580100300 ER PT J AU Amano, JE Subotnik, KL Ventura, J Gretchen-Doorly, D Casaus, LR Luo, JS Marder, SR Hellemann, GS Dunn, W Nuechterlein, KH AF Amano, Joshua E. Subotnik, Kenneth L. Ventura, Joseph Gretchen-Doorly, Denise Casaus, Laurie R. Luo, John S. Marder, Stephen R. Hellemann, Gerhard S. Dunn, Walter Nuechterlein, Keith H. TI Oral and long-acting injectable risperidone: Relationships among medication plasma levels, adherence, and clinical outcome in schizophrenia patients shortly after the initial psychotic episode SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Meeting Abstract C1 [Subotnik, Kenneth L.; Ventura, Joseph; Gretchen-Doorly, Denise; Casaus, Laurie R.; Luo, John S.; Marder, Stephen R.; Hellemann, Gerhard S.; Dunn, Walter; Nuechterlein, Keith H.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Amano, Joshua E.; Nuechterlein, Keith H.] Univ Calif Los Angeles, Los Angeles UCLA, Los Angeles, CA 90024 USA. [Marder, Stephen R.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1751-7885 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD OCT PY 2012 VL 6 SU 1 SI SI BP 101 EP 101 PG 1 WC Psychiatry SC Psychiatry GA 003AI UT WOS:000308580100380 ER PT J AU Woodberry, KA Mesholam-Gately, RI Wojcik, JD Cousins, A Gnong-Granato, A Friedman-Yakoobian, M Rodenhiser-Hill, J Serur, RA Hornbach, S Francis, G Min, G Tucker, L AF Woodberry, Kristen A. Mesholam-Gately, Raquelle I. Wojcik, Joanne D. Cousins, Ann Gnong-Granato, Andrea Friedman-Yakoobian, Michelle Rodenhiser-Hill, Janine Serur, Rachael A. Hornbach, Sarah Francis, Grace Min, Grace Tucker, Lynda TI Childhood onset of symptoms as reported by first episode schizophrenia and clinical high risk youth SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Meeting Abstract C1 [Woodberry, Kristen A.; Mesholam-Gately, Raquelle I.; Wojcik, Joanne D.; Cousins, Ann; Gnong-Granato, Andrea; Friedman-Yakoobian, Michelle; Rodenhiser-Hill, Janine; Serur, Rachael A.; Hornbach, Sarah; Francis, Grace; Min, Grace; Tucker, Lynda] Beth Israel Deaconess Med Ctr, Brockton, MA USA. [Mesholam-Gately, Raquelle I.; Wojcik, Joanne D.; Cousins, Ann; Gnong-Granato, Andrea; Friedman-Yakoobian, Michelle; Rodenhiser-Hill, Janine; Serur, Rachael A.; Hornbach, Sarah; Francis, Grace; Min, Grace; Tucker, Lynda] Harvard Univ, Sch Med, Brockton, MA 02401 USA. Brigham & Womens Hosp, Brockton, MA USA. Massachusetts Gen Hosp, Brockton, MA USA. Vet Adm Boston Healthcare, Brockton, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1751-7885 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD OCT PY 2012 VL 6 SU 1 SI SI BP 120 EP 120 PG 1 WC Psychiatry SC Psychiatry GA 003AI UT WOS:000308580100456 ER PT J AU Stuart, BK Fulford, D Vertinski, M McPherson, M Vinogradov, S Loewy, RL AF Stuart, Barbara K. Fulford, Daniel Vertinski, Mary McPherson, Meagan Vinogradov, Sophia Loewy, Rachel L. TI The discrepancy between the experience and expression of emotion as a risk marker for conversion to psychotic disorder SO EARLY INTERVENTION IN PSYCHIATRY LA English DT Meeting Abstract C1 [Stuart, Barbara K.; Fulford, Daniel; Vinogradov, Sophia; Loewy, Rachel L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Vertinski, Mary] Univ Nevada, Las Vegas, NV 89154 USA. [Vinogradov, Sophia] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1751-7885 J9 EARLY INTERV PSYCHIA JI Early Interv. Psychiatry PD OCT PY 2012 VL 6 SU 1 SI SI BP 122 EP 122 PG 1 WC Psychiatry SC Psychiatry GA 003AI UT WOS:000308580100464 ER EF