FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Shen, HS Dai, GC Luo, MY Duan, CJ Cai, WL Liang, D Wang, XH Zhu, DY Li, WR Qiu, JP AF Shen, Hesong Dai, Guochao Luo, Mingyue Duan, Chaijie Cai, Wenli Liang, Dan Wang, Xinhua Zhu, Dongyun Li, Wenru Qiu, Jianping TI Image Quality and Radiation Dose of CT Coronary Angiography with Automatic Tube Current Modulation and Strong Adaptive Iterative Dose Reduction Three-Dimensional (AIDR3D) SO PLOS ONE LA English DT Article ID FILTERED BACK-PROJECTION; COMPUTED-TOMOGRAPHY; RECONSTRUCTION TECHNIQUES; 3D AB Purpose To investigate image quality and radiation dose of CT coronary angiography (CTCA) scanned using automatic tube current modulation (ATCM) and reconstructed by strong adaptive iterative dose reduction three-dimensional (AIDR3D). Methods Eighty-four consecutive CTCA patients were collected for the study. All patients were scanned using ATCM and reconstructed with strong AIDR3D, standard AIDR3D and filtered back-projection (FBP) respectively. Two radiologists who were blinded to the patients' clinical data and reconstruction methods evaluated image quality. Quantitative image quality evaluation included image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). To evaluate image quality qualitatively, coronary artery is classified into 15 segments based on the modified guidelines of the American Heart Association. Qualitative image quality was evaluated using a 4-point scale. Radiation dose was calculated based on dose-length product. Results Compared with standard AIDR3D, strong AIDR3D had lower image noise, higher SNR and CNR, their differences were all statistically significant (P<0.05); compared with FBP, strong AIDR3D decreased image noise by 46.1%, increased SNR by 84.7%, and improved CNR by 82.2%, their differences were all statistically significant (P<0.05 or 0.001). Segments with diagnostic image quality for strong AIDR3D were 336 (100.0%), 486 (96.4%), and 394 (93.8%) in proximal, middle, and distal part respectively; whereas those for standard AIDR3D were 332 (98.8%), 472 (93.7%), 378 (90.0%), respectively; those for FBP were 217 (64.6%), 173 (34.3%), 114 (27.1%), respectively; total segments with diagnostic image quality in strong AIDR3D (1216, 96.5%) were higher than those of standard AIDR3D (1182, 93.8%) and FBP (504, 40.0%); the differences between strong AIDR3D and standard AIDR3D, strong AIDR3D and FBP were all statistically significant (P<0.05 or 0.001). The mean effective radiation dose was (2.55 +/- 1.21) mSv. Conclusion Compared with standard AIDR3D and FBP, CTCA with ATCM and strong AIDR3D could significantly improve both quantitative and qualitative image quality. C1 [Shen, Hesong; Luo, Mingyue; Liang, Dan; Wang, Xinhua; Zhu, Dongyun; Li, Wenru; Qiu, Jianping] Sun Yat Sen Univ, Affiliated Hosp 6, Dept Radiol, Guangzhou 510275, Guangdong, Peoples R China. [Shen, Hesong] Chongqing Canc Inst, Dept Radiol, Chongqing, Peoples R China. [Dai, Guochao] First Peoples Hosp Kashi Area, Imaging Ctr, Xinjiang, Peoples R China. [Duan, Chaijie] Tsinghua Univ, Grad Sch,Shenzhen, Biomed Engn Res Ctr, Shenzhen, Guangdong, Peoples R China. [Cai, Wenli] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Cai, Wenli] Harvard Univ, Sch Med, Boston, MA USA. RP Luo, MY (reprint author), Sun Yat Sen Univ, Affiliated Hosp 6, Dept Radiol, Guangzhou 510275, Guangdong, Peoples R China. EM myluo720@163.com FU National Natural Science Foundation of China [81230035]; Guangdong Provincial Science and Technology Programs [2013B051000016] FX This study was supported by the National Natural Science Foundation of China (81230035), (http://www.nsfc.gov.cn/); and Guangdong Provincial Science and Technology Programs (2013B051000016), (http://pro.gdstc.gov.cn/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 27 TC 1 Z9 1 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 23 PY 2015 VL 10 IS 11 AR e0142185 DI 10.1371/journal.pone.0142185 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CX7AW UT WOS:000365853900022 PM 26599111 ER PT J AU Slocum, C Gerrard, P Black-Schaffer, R Goldstein, R Singhal, A DiVita, MA Ryan, CM Mix, J Purohit, M Niewczyk, P Kazis, L Zafonte, R Schneider, JC AF Slocum, Chloe Gerrard, Paul Black-Schaffer, Randie Goldstein, Richard Singhal, Aneesh DiVita, Margaret A. Ryan, Colleen M. Mix, Jacqueline Purohit, Maulik Niewczyk, Paulette Kazis, Lewis Zafonte, Ross Schneider, Jeffrey C. TI Functional Status Predicts Acute Care Readmissions from Inpatient Rehabilitation in the Stroke Population SO PLOS ONE LA English DT Article ID HOSPITAL READMISSIONS; COMORBIDITY INDEX; BODY-COMPOSITION; PERFORMANCE; RISK; COMPLICATIONS; VALIDATION; DISCHARGE; HEALTH; INJURY AB Objective Acute care readmission risk is an increasingly recognized problem that has garnered significant attention, yet the reasons for acute care readmission in the inpatient rehabilitation population are complex and likely multifactorial. Information on both medical comorbidities and functional status is routinely collected for stroke patients participating in inpatient rehabilitation. We sought to determine whether functional status is a more robust predictor of acute care readmissions in the inpatient rehabilitation stroke population compared with medical comorbidities using a large, administrative data set. Methods A retrospective analysis of data from the Uniform Data System for Medical Rehabilitation from the years 2002 to 2011 was performed examining stroke patients admitted to inpatient rehabilitation facilities. A Basic Model for predicting acute care readmission risk based on age and functional status was compared with models incorporating functional status and medical comorbidities (Basic-Plus) or models including age and medical comorbidities alone (Age-Comorbidity). C-statistics were compared to evaluate model performance. Findings There were a total of 803,124 patients: 88,187 (11%) patients were transferred back to an acute hospital: 22,247 (2.8%) within 3 days, 43,481 (5.4%) within 7 days, and 85,431 (10.6%) within 30 days. The C-statistics for the Basic Model were 0.701, 0.672, and 0.682 at days 3, 7, and 30 respectively. As compared to the Basic Model, the best-performing Basic-Plus model was the Basic+Elixhauser model with C-statistics differences of +0.011, +0.011, and +0.012, and the best-performing Age-Comorbidity model was the Age+Elixhauser model with C-statistic differences of -0.124, -0.098, and -0.098 at days 3, 7, and 30 respectively. Conclusions Readmission models for the inpatient rehabilitation stroke population based on functional status and age showed better predictive ability than models based on medical comorbidities. C1 [Slocum, Chloe; Gerrard, Paul; Black-Schaffer, Randie; Goldstein, Richard; Zafonte, Ross; Schneider, Jeffrey C.] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02138 USA. [Slocum, Chloe; Gerrard, Paul; Black-Schaffer, Randie; Zafonte, Ross; Schneider, Jeffrey C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Singhal, Aneesh] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [DiVita, Margaret A.; Mix, Jacqueline; Niewczyk, Paulette] Uniform Data Syst Med Rehabil, Amherst, NY USA. [Niewczyk, Paulette] Daemen Coll, Hlth Care Studies Dept, Amherst, NY USA. [Ryan, Colleen M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Sumner Redstone Burn Ctr,Surg Serv, Boston, MA USA. [Ryan, Colleen M.] Shriners Hosp Children Boston, Boston, MA USA. [Purohit, Maulik] Ft Belvoir Community Hosp, Natl Intrepid Ctr Excellence, Intrepid Spirit 1, Neurorehabil & Traumat Brain Injury, Ft Belvoir, VA USA. [Kazis, Lewis] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. RP Schneider, JC (reprint author), Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02138 USA. EM jcschneider@partners.org NR 35 TC 1 Z9 1 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 23 PY 2015 VL 10 IS 11 AR e0142180 DI 10.1371/journal.pone.0142180 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CX7AW UT WOS:000365853900021 PM 26599009 ER PT J AU Chen, HC Ren, SX Clish, C Jain, M Mootha, V McCaffery, JM Chan, DC AF Chen, Hsiuchen Ren, Shuxun Clish, Clary Jain, Mohit Mootha, Vamsi McCaffery, J. Michael Chan, David C. TI Titration of mitochondrial fusion rescues Mff-deficient cardiomyopathy SO JOURNAL OF CELL BIOLOGY LA English DT Article ID DOMINANT OPTIC ATROPHY; CRE RECOMBINASE; PEROXISOMAL FISSION; MAMMALIAN-CELLS; DRP1; HEART; DIFFERENTIATION; RECRUITMENT; HOMEOSTASIS; MUTATIONS AB Defects in mitochondrial fusion or fission are associated with many pathologies, raising the hope that pharmacological manipulation of mitochondrial dynamics may have therapeutic benefit. This approach assumes that organ physiology can be restored by rebalancing mitochondrial dynamics, but this concept remains to be validated. We addressed this issue by analyzing mice deficient in Mff, a protein important for mitochondrial fission. Mff mutant mice die at 13 wk as a result of severe dilated cardiomyopathy leading to heart failure. Mutant tissue showed reduced mitochondrial density and respiratory chain activity along with increased mitophagy. Remarkably, concomitant deletion of the mitochondrial fusion gene Mfn1 completely rescued heart dysfunction, life span, and respiratory chain function. Our results show for the first time that retuning the balance of mitochondrial fusion and fission can restore tissue integrity and mitochondrial physiology at the whole-organ level. Examination of liver, testis, and cerebellum suggest, however, that the precise balance point of fusion and fission is cell type specific. C1 [Chen, Hsiuchen; Chan, David C.] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA. [Ren, Shuxun] Univ Calif Los Angeles, David Geffen Sch Med, Dept Anesthesiol, Los Angeles, CA 90095 USA. [Clish, Clary; Mootha, Vamsi] Broad Inst, Cambridge, MA 02142 USA. [Jain, Mohit; Mootha, Vamsi] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [McCaffery, J. Michael] Johns Hopkins Univ, Dept Biol, Integrated Imaging Ctr, Baltimore, MD 21218 USA. RP Chan, DC (reprint author), CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA. EM dchan@caltech.edu FU [RO1GM062967] FX This work was supported by grant RO1GM062967 (to D.C. Chan). NR 32 TC 6 Z9 6 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0021-9525 EI 1540-8140 J9 J CELL BIOL JI J. Cell Biol. PD NOV 23 PY 2015 VL 211 IS 4 BP 795 EP 805 DI 10.1083/jcb.201507035 PG 11 WC Cell Biology SC Cell Biology GA CX4YY UT WOS:000365708100012 PM 26598616 ER PT J AU Aaltonen, T Albrow, M Amerio, S Amidei, D Anastassov, A Annovi, A Antos, J Apollinari, G Appel, JA Arisawa, T Artikov, A Asaadi, J Ashmanskas, W Auerbach, B Aurisano, A Azfar, F Badgett, W Bae, T Barbaro-Galtieri, A Barnes, VE Barnett, BA Barria, P Bartos, P Bauce, M Bedeschi, F Behari, S Bellettini, G Bellinger, J Benjamin, D Beretvas, A Bhatti, A Bland, KR Blumenfeld, B Bocci, A Bodek, A Bortoletto, D Boudreau, J Boveia, A Brigliadori, L Bromberg, C Brucken, E Budagov, J Budd, HS Burkett, K Busetto, G Bussey, P Butti, P Buzatu, A Calamba, A Camarda, S Campanelli, M Canelli, F Carls, B Carlsmith, D Carosi, R Carrillo, S Casal, B Casarsa, M Castro, A Catastini, P Cauz, D Cavaliere, V Cerri, A Cerrito, L Chen, YC Chertok, M Chiarelli, G Chlachidze, G Cho, K Chokheli, D Clark, A Clarke, C Convery, ME Conway, J Corbo, M Cordelli, M Cox, CA Cox, DJ Cremonesi, M Cruz, D Cuevas, J Culbertson, R d'Ascenzo, N Datta, M de Barbaro, P Demortier, L Deninno, M D'Errico, M Devoto, F Di Canto, A Di Ruzza, B Dittmann, JR Donati, S D'Onofrio, M Dorigo, M Driutti, A Ebina, K Edgar, R Elagin, A Erbacher, R Errede, S Esham, B Farrington, S Ramos, JPF Field, R Flanagan, G Forrest, R Franklin, M Freeman, JC Frisch, H Funakoshi, Y Galloni, C Garfinkel, AF Garosi, P Gerberich, H Gerchtein, E Giagu, S Giakoumopoulou, V Gibson, K Ginsburg, CM Giokaris, N Giromini, P Glagolev, V Glenzinski, D Gold, M Goldin, D Golossanov, A Gomez, G Gomez-Ceballos, G Goncharov, M Lopez, OG Gorelov, I Goshaw, AT Goulianos, K Gramellini, E Grosso-Pilcher, C Group, RC da Costa, JG Hahn, SR Han, JY Happacher, F Hara, K Hare, M Harr, RF Harrington-Taber, T Hatakeyama, K Hays, C Heinrich, J Herndon, M Hocker, A Hong, Z Hopkins, W Hou, S Hughes, RE Husemann, U Hussein, M Huston, J Introzzi, G Iori, M Ivanov, A James, E Jang, D Jayatilaka, B Jeon, EJ Jindariani, S Jones, M Joo, KK Jun, SY Junk, TR Kambeitz, M Kamon, T Karchin, PE Kasmi, A Kato, Y Ketchum, W Keung, J Kilminster, B Kim, DH Kim, HS Kim, JE Kim, MJ Kim, SH Kim, SB Kim, YJ Kim, YK Kimura, N Kirby, M Knoepfel, K Kondo, K Kong, DJ Konigsberg, J Kotwal, AV Kreps, M Kroll, J Kruse, M Kuhr, T Kurata, M Laasanen, AT Lammel, S Lancaster, M Lannon, K Latino, G Lee, HS Lee, JS Leo, S Leone, S Lewis, JD Limosani, A Lipeles, E Lister, A Liu, H Liu, Q Liu, T Lockwitz, S Loginov, A Lucchesi, D Luca, A Lueck, J Lujan, P Lukens, P Lungu, G Lys, J Lysak, R Madrak, R Maestro, P Malik, S Manca, G Manousakis-Katsikakis, A Marchese, L Margaroli, F Marino, P Matera, K Mattson, ME Mazzacane, A Mazzanti, P McNulty, R Mehta, A Mehtala, P Mesropian, C Miao, T Mietlicki, D Mitra, A Miyake, H Moed, S Moggi, N Moon, CS Moore, R Morello, MJ Mukherjee, A Muller, T Murat, P Mussini, M Nachtman, J Nagai, Y Naganoma, J Nakano, I Napier, A Nett, J Neu, C Nigmanov, T Nodulman, L Noh, SY Norniella, O Oakes, L Oh, SH Oh, YD Oksuzian, I Okusawa, T Orava, R Ortolan, L Pagliarone, C Palencia, E Palni, P Papadimitriou, V Parker, W Pauletta, G Paulini, M Paus, C Phillips, TJ Piacentino, G Pianori, E Pilot, J Pitts, K Plager, C Pondrom, L Poprocki, S Potamianos, K Pranko, A Prokoshin, F Ptohos, F Punzi, G Fernandez, IR Renton, P Rescigno, M Rimondi, F Ristori, L Robson, A Rodriguez, T Rolli, S Ronzani, M Roser, R Rosner, JL Ruffini, F Ruiz, A Russ, J Rusu, V Sakumoto, WK Sakurai, Y Santi, L Sato, K Saveliev, V Savoy-Navarro, A Schlabach, P Schmidt, EE Schwarz, T Scodellaro, L Scuri, F Seidel, S Seiya, Y Semenov, A Sforza, F Shalhout, SZ Shears, T Shepard, PF Shimojima, M Shochet, M Shreyber-Tecker, I Simonenko, A Sliwa, K Smith, JR Snider, FD Song, H Sorin, V Denis, RS Stancari, M Stentz, D Strologas, J Sudo, Y Sukhanov, A Suslov, I Takemasa, K Takeuchi, Y Tang, J Tecchio, M Teng, PK Thom, J Thomson, E Thukral, V Toback, D Tokar, S Tollefson, K Tomura, T Tonelli, D Torre, S Torretta, D Totaro, P Trovato, M Ukegawa, F Uozumi, S Vazquez, F Velev, G Vellidis, C Vernieri, C Vidal, M Vilar, R Vizan, J Vogel, M Volpi, G Wagner, P Wallny, R Wang, SM Waters, D Wester, WC Whiteson, D Wicklund, AB Wilbur, S Williams, HH Wilson, JS Wilson, P Winer, BL Wittich, P Wolbers, S Wolfe, H Wright, T Wu, X Wu, Z Yamamoto, K Yamato, D Yang, T Yang, UK Yang, YC Yao, WM Yeh, GP Yi, K Yoh, J Yorita, K Yoshida, T Yu, GB Yu, I Zanetti, AM Zeng, Y Zhou, C Zucchelli, S AF Aaltonen, T. Albrow, M. Amerio, S. Amidei, D. Anastassov, A. Annovi, A. Antos, J. Apollinari, G. Appel, J. A. Arisawa, T. Artikov, A. Asaadi, J. Ashmanskas, W. Auerbach, B. Aurisano, A. Azfar, F. Badgett, W. Bae, T. Barbaro-Galtieri, A. Barnes, V. E. Barnett, B. A. Barria, P. Bartos, P. Bauce, M. Bedeschi, F. Behari, S. Bellettini, G. Bellinger, J. Benjamin, D. Beretvas, A. Bhatti, A. Bland, K. R. Blumenfeld, B. Bocci, A. Bodek, A. Bortoletto, D. Boudreau, J. Boveia, A. Brigliadori, L. Bromberg, C. Brucken, E. Budagov, J. Budd, H. S. Burkett, K. Busetto, G. Bussey, P. Butti, P. Buzatu, A. Calamba, A. Camarda, S. Campanelli, M. Canelli, F. Carls, B. Carlsmith, D. Carosi, R. Carrillo, S. Casal, B. Casarsa, M. Castro, A. Catastini, P. Cauz, D. Cavaliere, V. Cerri, A. Cerrito, L. Chen, Y. C. Chertok, M. Chiarelli, G. Chlachidze, G. Cho, K. Chokheli, D. Clark, A. Clarke, C. Convery, M. E. Conway, J. Corbo, M. Cordelli, M. Cox, C. A. Cox, D. J. Cremonesi, M. Cruz, D. Cuevas, J. Culbertson, R. d'Ascenzo, N. Datta, M. de Barbaro, P. Demortier, L. Deninno, M. D'Errico, M. Devoto, F. Di Canto, A. Di Ruzza, B. Dittmann, J. R. Donati, S. D'Onofrio, M. Dorigo, M. Driutti, A. Ebina, K. Edgar, R. Elagin, A. Erbacher, R. Errede, S. Esham, B. Farrington, S. Fernandez Ramos, J. P. Field, R. Flanagan, G. Forrest, R. Franklin, M. Freeman, J. C. Frisch, H. Funakoshi, Y. Galloni, C. Garfinkel, A. F. Garosi, P. Gerberich, H. Gerchtein, E. Giagu, S. Giakoumopoulou, V. Gibson, K. Ginsburg, C. M. Giokaris, N. Giromini, P. Glagolev, V. Glenzinski, D. Gold, M. Goldin, D. Golossanov, A. Gomez, G. Gomez-Ceballos, G. Goncharov, M. Lopez, O. Gonzalez Gorelov, I. Goshaw, A. T. Goulianos, K. Gramellini, E. Grosso-Pilcher, C. Group, R. C. da Costa, J. Guimaraes Hahn, S. R. Han, J. Y. Happacher, F. Hara, K. Hare, M. Harr, R. F. Harrington-Taber, T. Hatakeyama, K. Hays, C. Heinrich, J. Herndon, M. Hocker, A. Hong, Z. Hopkins, W. Hou, S. Hughes, R. E. Husemann, U. Hussein, M. Huston, J. Introzzi, G. Iori, M. Ivanov, A. James, E. Jang, D. Jayatilaka, B. Jeon, E. J. Jindariani, S. Jones, M. Joo, K. K. Jun, S. Y. Junk, T. R. Kambeitz, M. Kamon, T. Karchin, P. E. Kasmi, A. Kato, Y. Ketchum, W. Keung, J. Kilminster, B. Kim, D. H. Kim, H. S. Kim, J. E. Kim, M. J. Kim, S. H. Kim, S. B. Kim, Y. J. Kim, Y. K. Kimura, N. Kirby, M. Knoepfel, K. Kondo, K. Kong, D. J. Konigsberg, J. Kotwal, A. V. Kreps, M. Kroll, J. Kruse, M. Kuhr, T. Kurata, M. Laasanen, A. T. Lammel, S. Lancaster, M. Lannon, K. Latino, G. Lee, H. S. Lee, J. S. Leo, S. Leone, S. Lewis, J. D. Limosani, A. Lipeles, E. Lister, A. Liu, H. Liu, Q. Liu, T. Lockwitz, S. Loginov, A. Lucchesi, D. Luca, A. Lueck, J. Lujan, P. Lukens, P. Lungu, G. Lys, J. Lysak, R. Madrak, R. Maestro, P. Malik, S. Manca, G. Manousakis-Katsikakis, A. Marchese, L. Margaroli, F. Marino, P. Matera, K. Mattson, M. E. Mazzacane, A. Mazzanti, P. McNulty, R. Mehta, A. Mehtala, P. Mesropian, C. Miao, T. Mietlicki, D. Mitra, A. Miyake, H. Moed, S. Moggi, N. Moon, C. S. Moore, R. Morello, M. J. Mukherjee, A. Muller, Th. Murat, P. Mussini, M. Nachtman, J. Nagai, Y. Naganoma, J. Nakano, I. Napier, A. Nett, J. Neu, C. Nigmanov, T. Nodulman, L. Noh, S. Y. Norniella, O. Oakes, L. Oh, S. H. Oh, Y. D. Oksuzian, I. Okusawa, T. Orava, R. Ortolan, L. Pagliarone, C. Palencia, E. Palni, P. Papadimitriou, V. Parker, W. Pauletta, G. Paulini, M. Paus, C. Phillips, T. J. Piacentino, G. Pianori, E. Pilot, J. Pitts, K. Plager, C. Pondrom, L. Poprocki, S. Potamianos, K. Pranko, A. Prokoshin, F. Ptohos, F. Punzi, G. Redondo Fernandez, I. Renton, P. Rescigno, M. Rimondi, F. Ristori, L. Robson, A. Rodriguez, T. Rolli, S. Ronzani, M. Roser, R. Rosner, J. L. Ruffini, F. Ruiz, A. Russ, J. Rusu, V. Sakumoto, W. K. Sakurai, Y. Santi, L. Sato, K. Saveliev, V. Savoy-Navarro, A. Schlabach, P. Schmidt, E. E. Schwarz, T. Scodellaro, L. Scuri, F. Seidel, S. Seiya, Y. Semenov, A. Sforza, F. Shalhout, S. Z. Shears, T. Shepard, P. F. Shimojima, M. Shochet, M. Shreyber-Tecker, I. Simonenko, A. Sliwa, K. Smith, J. R. Snider, F. D. Song, H. Sorin, V. Denis, R. St. Stancari, M. Stentz, D. Strologas, J. Sudo, Y. Sukhanov, A. Suslov, I. Takemasa, K. Takeuchi, Y. Tang, J. Tecchio, M. Teng, P. K. Thom, J. Thomson, E. Thukral, V. Toback, D. Tokar, S. Tollefson, K. Tomura, T. Tonelli, D. Torre, S. Torretta, D. Totaro, P. Trovato, M. Ukegawa, F. Uozumi, S. Vazquez, F. Velev, G. Vellidis, C. Vernieri, C. Vidal, M. Vilar, R. Vizan, J. Vogel, M. Volpi, G. Wagner, P. Wallny, R. Wang, S. M. Waters, D. Wester, W. C., III Whiteson, D. Wicklund, A. B. Wilbur, S. Williams, H. H. Wilson, J. S. Wilson, P. Winer, B. L. Wittich, P. Wolbers, S. Wolfe, H. Wright, T. Wu, X. Wu, Z. Yamamoto, K. Yamato, D. Yang, T. Yang, U. K. Yang, Y. C. Yao, W. -M. Yeh, G. P. Yi, K. Yoh, J. Yorita, K. Yoshida, T. Yu, G. B. Yu, I. Zanetti, A. M. Zeng, Y. Zhou, C. Zucchelli, S. TI Study of the energy dependence of the underlying event in proton-antiproton collisions SO PHYSICAL REVIEW D LA English DT Article AB We study charged particle production (p(T) > 0.5 GeV/c, vertical bar eta vertical bar < 0.8) in proton-antiproton collisions at total center-of-mass energies root s = 300 GeV, 900 GeV, and 1.96 TeV. We use the direction of the charged particle with the largest transverse momentum in each event to define three regions of eta - phi space: "toward", "away", and "transverse." The average number and the average scalar pT sum of charged particles in the transverse region are sensitive to the modeling of the "underlying event." The transverse region is divided into a MAX and MIN transverse region, which helps separate the "hard component" (initial and final-state radiation) from the "beam-beam remnant" and multiple parton interaction components of the scattering. The center-of-mass energy dependence of the various components of the event is studied in detail. The data presented here can be used to constrain and improve QCD Monte Carlo models, resulting in more precise predictions at the LHC energies of 13 and 14 TeV. C1 [Chen, Y. C.; Hou, S.; Mitra, A.; Teng, P. K.; Wang, S. M.] Acad Sinica, Inst Phys, Taipei 11529, Taiwan. [Auerbach, B.; Nodulman, L.; Wicklund, A. B.] Argonne Natl Lab, Argonne, IL 60439 USA. [Giakoumopoulou, V.; Giokaris, N.; Manousakis-Katsikakis, A.] Univ Athens, GR-15771 Athens, Greece. [Camarda, S.; Ortolan, L.; Sorin, V.] Univ Autonoma Barcelona, ICREA, Inst Fis Altes Energies, E-08193 Bellaterra, Barcelona, Spain. [Bland, K. R.; Dittmann, J. R.; Hatakeyama, K.; Kasmi, A.; Wu, Z.] Baylor Univ, Waco, TX 76798 USA. [Brigliadori, L.; Castro, A.; Deninno, M.; Gramellini, E.; Marchese, L.; Mazzanti, P.; Moggi, N.; Mussini, M.; Rimondi, F.] Ist Nazl Fis Nucl, I-40127 Bologna, Italy. [Brigliadori, L.; Castro, A.; Mussini, M.] Univ Bologna, I-40127 Bologna, Italy. [Chertok, M.; Conway, J.; Cox, C. A.; Cox, D. J.; Erbacher, R.; Forrest, R.; Ivanov, A.; Pilot, J.; Shalhout, S. Z.; Smith, J. R.; Wilbur, S.] Univ Calif Davis, Davis, CA 95616 USA. [Plager, C.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Casal, B.; Cuevas, J.; Gomez, G.; Palencia, E.; Ruiz, A.; Scodellaro, L.; Vilar, R.; Vizan, J.] Univ Cantabria, CSIC, Inst Fis Cantabria, E-39005 Santander, Spain. [Calamba, A.; Jang, D.; Jun, S. Y.; Paulini, M.; Russ, J.] Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. [Boveia, A.; Canelli, F.; Frisch, H.; Grosso-Pilcher, C.; Ketchum, W.; Kim, Y. K.; Rosner, J. L.; Shochet, M.; Tang, J.] Univ Chicago, Enrico Fermi Inst, Chicago, IL 60637 USA. [Antos, J.; Bartos, P.; Lysak, R.; Tokar, S.] Comenius Univ, Bratislava 84248, Slovakia. [Antos, J.; Bartos, P.; Lysak, R.; Tokar, S.] Inst Expt Phys, Kosice 04001, Slovakia. 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[Vizan, J.] Catholic Univ Louvain, B-1348 Louvain La Neuve, Belgium. [Canelli, F.; Kilminster, B.] Univ Zurich, CH-8006 Zurich, Switzerland. [Moore, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Moore, R.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Datta, M.] Hampton Univ, Hampton, VA 23668 USA. [Ketchum, W.] Los Alamos Natl Lab, Los Alamos, NM 87544 USA. [Marchese, L.] Univ Napoli Federico I, I-80138 Naples, Italy. RP Aaltonen, T (reprint author), Univ Helsinki, Dept Phys, Div High Energy Phys, FIN-00014 Helsinki, Finland. RI maestro, paolo/E-3280-2010; Paulini, Manfred/N-7794-2014; Martinez, Mario /I-3549-2015; Chiarelli, Giorgio/E-8953-2012; Prokoshin, Fedor/E-2795-2012; Marino, Pietro/N-7030-2015; Canelli, Florencia/O-9693-2016; Ruiz, Alberto/E-4473-2011; OI Dorigo, Mirco/0000-0002-0681-6946; Brucken, Jens Erik/0000-0001-6066-8756; maestro, paolo/0000-0002-4193-1288; Paulini, Manfred/0000-0002-6714-5787; Devoto, Francesco/0000-0002-3415-7677; Group, Robert/0000-0002-4097-5254; Simonenko, Alexander/0000-0001-6580-3638; Farrington, Sinead/0000-0001-5350-9271; Chiarelli, Giorgio/0000-0001-9851-4816; Prokoshin, Fedor/0000-0001-6389-5399; Marino, Pietro/0000-0003-0554-3066; Canelli, Florencia/0000-0001-6361-2117; Ruiz, Alberto/0000-0002-3639-0368; Robson, Aidan/0000-0002-1659-8284 FU U.S. Department of Energy; National Science Foundation; Italian Istituto Nazionale di Fisica Nucleare; Ministry of Education, Culture, Sports, Science and Technology of Japan; Natural Sciences and Engineering Research Council of Canada; National Science Council of the Republic of China; Swiss National Science Foundation; A. P. Sloan Foundation; Bundesministerium fur Bildung und Forschung, Germany; Korean World Class University Program; National Research Foundation of Korea; Science and Technology Facilities Council; Royal Society, United Kingdom; Russian Foundation for Basic Research; Ministerio de Ciencia e Innovacion; Programa Consolider-Ingenio, Spain; Slovak RD Agency; Academy of Finland; Australian Research Council (ARC); EU community Marie Curie Fellowship [302103] FX We thank the Fermilab staff and the technical staffs of the participating institutions for their vital contributions. This work was supported by the U.S. Department of Energy and National Science Foundation; the Italian Istituto Nazionale di Fisica Nucleare; the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Natural Sciences and Engineering Research Council of Canada; the National Science Council of the Republic of China; the Swiss National Science Foundation; the A. P. Sloan Foundation; the Bundesministerium fur Bildung und Forschung, Germany; the Korean World Class University Program, the National Research Foundation of Korea; the Science and Technology Facilities Council and the Royal Society, United Kingdom; the Russian Foundation for Basic Research; the Ministerio de Ciencia e Innovacion, and Programa Consolider-Ingenio 2010, Spain; the Slovak R&D Agency; the Academy of Finland; the Australian Research Council (ARC); and the EU community Marie Curie Fellowship Contract No. 302103. NR 18 TC 0 Z9 0 U1 2 U2 20 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1550-7998 EI 1550-2368 J9 PHYS REV D JI Phys. Rev. D PD NOV 23 PY 2015 VL 92 IS 9 AR 092009 DI 10.1103/PhysRevD.92.092009 PG 21 WC Astronomy & Astrophysics; Physics, Particles & Fields SC Astronomy & Astrophysics; Physics GA CX2FH UT WOS:000365510800002 ER PT J AU Si, J Lee, S Park, JM Sung, J Ko, G AF Si, Jiyeon Lee, Sunghee Park, Jin Mo Sung, Joohon Ko, GwangPyo TI Genetic associations and shared environmental effects on the skin microbiome of Korean twins SO BMC GENOMICS LA English DT Article DE Skin microbiota; Heritability; Twin study; Host genetics; Common environment effect ID LACTIC-ACID BACTERIA; MOLECULAR ANALYSIS; GUT MICROBIOME; HEALTHY TWIN; DIVERSITY; DISEASE; MELANOGENESIS; COMMUNITIES; POPULATION; ALIGNMENTS AB Background: The skin is the outermost layer of the human body and one of the key sites for host-microbe interactions. Both environmental and host genetic factors influence microbial communities in distinct anatomical niches, but little is known about their interplay in shaping the skin microbiome. Here, we investigate the heritable components of the skin microbiome and their association with host genetic factors. Results: Based on our analysis of the microbiota from 45 individuals including monozygotic and dizygotic twins aged 26-55 years and their mothers, we found that skin microbial diversity was significantly influenced by age and skin pigmentation. Heritability analysis revealed genetic and shared environmental impacts on the skin microbiome. Furthermore, we observed a strong association between the abundance of Corynebacterium jeikeium and single nucleotide polymorphisms (SNPs) in the host FLG gene related to epidermal barrier function. Conclusion: This study reveals an intimate association of the human skin microbiome and host genes, and increases our understanding of the role of human genetic factors in establishing a microbial ecosystem on the body surface. C1 [Si, Jiyeon; Lee, Sunghee; Ko, GwangPyo] Seoul Natl Univ, Sch Publ Hlth, Dept Environm Hlth, Seoul 151742, South Korea. [Park, Jin Mo] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Park, Jin Mo] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Sung, Joohon] Seoul Natl Univ, Sch Publ Hlth, Dept Epidemiol, Seoul 151742, South Korea. RP Sung, J (reprint author), Seoul Natl Univ, Sch Publ Hlth, Dept Epidemiol, 1 Gwanak Ro, Seoul 151742, South Korea. EM jsung@snu.ac.kr; gko@snu.ac.kr FU National Research Foundation of Korea (NRF) grant - Korean government (MEST) [2010-0029113] FX This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (No. 2010-0029113). NR 65 TC 7 Z9 7 U1 3 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD NOV 23 PY 2015 VL 16 AR 992 DI 10.1186/s12864-015-2131-y PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA CW8YM UT WOS:000365285400006 PM 26596276 ER PT J AU Heo, SJ Thorpe, SD Driscoll, TP Duncan, RL Lee, DA Mauck, RL AF Heo, Su-Jin Thorpe, Stephen D. Driscoll, Tristan P. Duncan, Randall L. Lee, David A. Mauck, Robert L. TI Biophysical Regulation of Chromatin Architecture Instills a Mechanical Memory in Mesenchymal Stem Cells SO SCIENTIFIC REPORTS LA English DT Article ID INDUCED OSTEOGENIC DIFFERENTIATION; MECHANOTRANSDUCTION PATHWAY; LINEAGE SPECIFICATION; HISTONE MODIFICATIONS; GENE-EXPRESSION; FLUID-FLOW; NUCLEUS; ATP; CHONDROCYTES; CYTOSKELETON AB Mechanical cues direct the lineage commitment of mesenchymal stem cells (MSCs). In this study, we identified the operative molecular mechanisms through which dynamic tensile loading (DL) regulates changes in chromatin organization and nuclear mechanics in MSCs. Our data show that, in the absence of exogenous differentiation factors, short term DL elicits a rapid increase in chromatin condensation, mediated by acto-myosin based cellular contractility and the activity of the histone-lysine N-methyltransferase EZH2. The resulting change in chromatin condensation stiffened the MSC nucleus, making it less deformable when stretch was applied to the cell. We also identified stretch induced ATP release and purinergic calcium signaling as a central mediator of this chromatin condensation process. Further, we showed that DL, through differential stabilization of the condensed chromatin state, established a 'mechanical memory' in these cells. That is, increasing strain levels and number of loading events led to a greater degree of chromatin condensation that persisted for longer periods of time after the cessation of loading. These data indicate that, with mechanical perturbation, MSCs develop a mechanical memory encoded in structural changes in the nucleus which may sensitize them to future mechanical loading events and define the trajectory and persistence of their lineage specification. C1 [Heo, Su-Jin; Driscoll, Tristan P.; Mauck, Robert L.] Univ Penn, McKay Orthopaed Res Lab, Dept Orthopaed Surg, Perelman Sch Med, Philadelphia, PA 19104 USA. [Heo, Su-Jin; Driscoll, Tristan P.; Mauck, Robert L.] Univ Penn, Dept Bioengn, Sch Engn & Appl Sci, Philadelphia, PA 19104 USA. [Thorpe, Stephen D.; Lee, David A.] Queen Mary Univ London, Inst Bioengn, Sch Engn & Mat Sci, London, England. [Driscoll, Tristan P.; Mauck, Robert L.] Philadelphia VA Med Ctr, Translat Musculoskeletal Res Ctr, Philadelphia, PA USA. [Duncan, Randall L.] Univ Delaware, Dept Biol Sci, Newark, DE USA. RP Mauck, RL (reprint author), Univ Penn, McKay Orthopaed Res Lab, Dept Orthopaed Surg, Perelman Sch Med, Philadelphia, PA 19104 USA. EM lemauck@mail.med.upenn.edu OI Driscoll, Tristan/0000-0002-2426-5551; Thorpe, Stephen/0000-0002-4707-7756 FU National Institutes of Health [R01 AR056624, R01 EB02425, T32 AR007132, P30 AR050950]; Marie Curie Intra European Fellowship (GENOMICDIFF) [301509]; Montague Research Award from the Perelman School of Medicine; University of Pennsylvania University Research Foundation Award FX This work was supported by the National Institutes of Health (R01 AR056624, R01 EB02425, T32 AR007132, and P30 AR050950) and a Marie Curie Intra European Fellowship (GENOMICDIFF, grant No. 301509). Additional support was provided by a Montague Research Award from the Perelman School of Medicine and a University of Pennsylvania University Research Foundation Award. The authors would like to gratefully acknowledge Dr. Woojin Han for assistance in calcium imaging studies. NR 54 TC 6 Z9 6 U1 5 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD NOV 23 PY 2015 VL 5 AR 16895 DI 10.1038/srep16895 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW6EC UT WOS:000365089300001 PM 26592929 ER PT J AU Garg, AD Galluzzi, L Apetoh, L Baert, T Birge, RB Bravo-San Pedro, JM Breckpot, K Brough, D Chaurio, R Cirone, M Coosemans, A Coulie, PG De Ruysscher, D Dini, L de Witte, P Dudek-Peric, AM Faggioni, A Fucikova, J Gaipl, US Golab, J Gougeon, ML Hamblin, MR Hemminki, A Herrmann, M Hodge, JW Kepp, O Kroemer, G Krysko, DV Land, WG Madeo, F Manfredi, AA Mattarollo, SR Maueroder, C Merendino, N Multhoff, G Pabst, T Ricci, JE Riganti, C Romano, E Rufo, N Smyth, MJ Sonnemann, J Spisek, R Stagg, J Vacchelli, E Vandenabeele, P Vandenberk, L Van den Eynde, BJ Van Gool, S Velotti, F Zitvogel, L Agostinis, P AF Garg, Abhishek D. Galluzzi, Lorenzo Apetoh, Lionel Baert, Thais Birge, Raymond B. Bravo-San Pedro, Jose Manuel Breckpot, Karine Brough, David Chaurio, Ricardo Cirone, Mara Coosemans, An Coulie, Pierre G. De Ruysscher, Dirk Dini, Luciana de Witte, Peter Dudek-Peric, Aleksandra M. Faggioni, Alberto Fucikova, Jitka Gaipl, Udo S. Golab, Jakub Gougeon, Marie-Lise Hamblin, Michael R. Hemminki, Akseli Herrmann, Martin Hodge, James W. Kepp, Oliver Kroemer, Guido Krysko, Dmitri V. Land, Walter G. Madeo, Frank Manfredi, Angelo A. Mattarollo, Stephen R. Maueroder, Christian Merendino, Nicolo Multhoff, Gabriele Pabst, Thomas Ricci, Jean-Ehrland Riganti, Chiara Romano, Erminia Rufo, Nicole Smyth, Mark J. Sonnemann, Juergen Spisek, Radek Stagg, John Vacchelli, Erika Vandenabeele, Peter Vandenberk, Lien Van den Eynde, Benoit J. Van Gool, Stefaan Velotti, Francesca Zitvogel, Laurence Agostinis, Patrizia TI Molecular and Translational Classifications of DAMPs in Immunogenic Cell Death SO FRONTIERS IN IMMUNOLOGY LA English DT Article DE anti-tumor immunity; immunogenicity; immunotherapy; molecular dicine; oncoimmunology; patient prognosis; translational medicine ID HUMAN TUMOR-CELLS; HIGH HYDROSTATIC-PRESSURE; APOPTOTIC CALRETICULIN EXPOSURE; ANTICANCER IMMUNE-RESPONSES; ACTIVATING POLYPEPTIDE-II; FORMYL PEPTIDE RECEPTORS; RIBOSOMAL-PROTEIN DIMER; CYTOTOXIC T-LYMPHOCYTES; NEGATIVE BREAST-CANCER; PHOTODYNAMIC THERAPY AB The immunogenicity of malignant cells has recently been acknowledged as a critical determinant of efficacy in cancer therapy. Thus, besides developing direct immunostimulatory regimens, including dendritic cell-based vaccines, checkpoint-blocking therapies, and adoptive T-cell transfer, researchers have started to focus on the overall mmunobiology of neoplastic cells. It is now clear that cancer cells can succumb to some anticancer therapies by undergoing a peculiar form of cell death that is characterized by an increased immunogenic potential, owing to the emission of the so-called "damage-associated molecular patterns" (DAMPs). The emission of DAMPs and other mmunostimulatory factors by cells succumbing to immunogenic cell death (ICD) favors the establishment of a productive interface with the immune system. This results in the elicitation of tumor-targeting immune responses associated with the elimination of residual, treatment-resistant cancer cells, as well as with the establishment of immunological memory. Although ICD has been characterized with increased precision since its discovery, several questions remain to be addressed. Here, we summarize and tabulate the main molecular, immunological, preclinical, and clinical aspects of ICD, in an attempt to capture the essence of this phenomenon, and identify future challenges for this rapidly expanding field of investigation. C1 [Garg, Abhishek D.; Romano, Erminia; Rufo, Nicole; Agostinis, Patrizia] Univ Leuven, KU Leuven, Dept Cellular Mol Med, Cell Death Res & Therapy, Leuven, Belgium. [Galluzzi, Lorenzo; Bravo-San Pedro, Jose Manuel; Vacchelli, Erika] Ctr Rech Cordefiers, Equipe Labelsee Ligue Canc 11, Paris, France. [Galluzzi, Lorenzo; Bravo-San Pedro, Jose Manuel; Vacchelli, Erika] INSERM, U1138, Paris, France. [Galluzzi, Lorenzo; Bravo-San Pedro, Jose Manuel; Vacchelli, Erika] Univ Paris 05, Sorbonne Paris Cite, Paris, France. [Galluzzi, Lorenzo; Bravo-San Pedro, Jose Manuel; Vacchelli, Erika] Univ Paris 06, Paris, France. [Galluzzi, Lorenzo; Bravo-San Pedro, Jose Manuel; Vacchelli, Erika; Van den Eynde, Benoit J.] Gustave Roussy Comprehens Canc Inst, Villejuif, France. [Apetoh, Lionel] INSERM, U866, Dijon, France. [Apetoh, Lionel] Univ Bourgogne, Fac Med, Dijon, France. [Apetoh, Lionel] Ctr Georges Francois Leclerc, Dijon, France. [Baert, Thais; Coosemans, An] UZ Leuven, Dept Gynaecol & Obstet, Leuven, Belgium. [Baert, Thais; Coosemans, An] Katholieke Univ Leuven, Leuven Canc Inst, Dept Oncol, Lab Gynaecol Oncol, Leuven, Belgium. [Birge, Raymond B.] Univ Med & Dent New Jersey, New Jersey Med Sch, Rutgers Canc Inst New Jersey, Univ Hosp Canc Ctr,Dept Microbiol Biochem & Mol G, Newark, NJ 07103 USA. [Breckpot, Karine] Vrije Univ Brussel, Lab Mol & Cellular Therapy, Jette, Belgium. [Brough, David] Univ Manchester, Fac Life Sci, Manchester, Lancs, England. [Chaurio, Ricardo; Herrmann, Martin; Maueroder, Christian] Univ Erlangen Nurnberg, Dept Internal Med Rheumatol & Immunol 3, D-91054 Erlangen, Germany. [Cirone, Mara] Univ Roma La Sapienza, Dept Expt Med, I-00185 Rome, Italy. [Coulie, Pierre G.] Catholic Univ Louvain, Duve Inst, B-1200 Brussels, Belgium. [De Ruysscher, Dirk] Univ Leuven, KU Leuven, Univ Hosp Leuven, Dept Radiat Oncol, Leuven, Belgium. [Dini, Luciana] Univ Salento, Dept Biol & Environm Sci & Technol, Salento, Italy. [de Witte, Peter] Univ Leuven, KU Leuven, Dept Pharmaceut & Pharmacol Sci, Lab Mol Biodiscovery, Leuven, Belgium. [Faggioni, Alberto] Univ Roma La Sapienza, I-00185 Rome, Italy. [Fucikova, Jitka; Spisek, Radek] SOTIO, Prague, Czech Republic. [Fucikova, Jitka; Spisek, Radek] Charles Univ Prague, Univ Hosp Motol, Fac Med 2, Dept Immunol, Prague, Czech Republic. [Gaipl, Udo S.] Univ Klinikum Erlangen, Dept Radiat Oncol, Erlangen, Germany. [Golab, Jakub] Med Univ Warsaw, Dept Immunol, Warsaw, Poland. [Gougeon, Marie-Lise] Inst Pasteur, Biotherapy & Vaccine Unit, Paris, France. [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hemminki, Akseli] Univ Helsinki, Haartman Inst, Transplantat Lab, Canc Gene Therapy Grp, Helsinki, Finland. [Hemminki, Akseli] Helsinki Univ Hosp, Ctr Comprehens Canc, Helsinki, Finland. [Hemminki, Akseli] TILT Biotherapeut Ltd, Helsinki, Finland. [Hodge, James W.] NCI, NIH, Recombinant Vaccine Grp, Lab Tumor Immunol & Biol, Bethesda, MD 20892 USA. [Kepp, Oliver; Kroemer, Guido] Gustave Roussy Comprehens Canc Inst, Metabolom & Cell Biol Platforms, Villejuif, France. [Kroemer, Guido] Hop Europeen Georges Pompidou, AP HP, Pole Biol, Paris, France. [Kroemer, Guido] Karolinska Univ Hosp, Dept Womens & Chlldrens Hlth, Stockholm, Sweden. [Krysko, Dmitri V.; Vandenabeele, Peter] VIB, Inflammat Res Ctr, Mol Signaling & Cell Death Unit, Ghent, Belgium. [Krysko, Dmitri V.; Vandenabeele, Peter] Univ Ghent, Dept Biomed Mol Biol, B-9000 Ghent, Belgium. [Land, Walter G.] Univ Strasbourg, Lab Excellence Transplantex, INSERM UMRS1109, Mol ImmunoRheumatol, Strasbourg, France. [Madeo, Frank] Graz Univ, NAWI Graz, lnst Mol Biosci, Graz, Austria. [Madeo, Frank] BioTechMed Graz, Graz, Austria. [Manfredi, Angelo A.] Univ Vita Salute San Raffaele, IRRCS Ist Sci San Raffaele, Milan, Italy. [Mattarollo, Stephen R.] Univ Queensland, Univ Queensland Diamantina Inst, Translat Res Inst, Woolloongabba, Qld, Australia. [Merendino, Nicolo] Univ Tuscia, Dept Ecol & Biol Sci, Lab Cellular & Mol Nutr, Viterbo, Italy. [Multhoff, Gabriele] Tech Univ Munich, Klinikum Rechts Isar, Dept Radiat Oncol, D-80290 Munich, Germany. [Pabst, Thomas] Univ Hosp, Dept Med Oncol, Bern, Switzerland. [Ricci, Jean-Ehrland] Univ Nice Sophia Antipolis, IAISERM U1065, Ctr Med Med Mol C3M Equipe Controle Metabol Morts, F-06189 Nice, France. [Riganti, Chiara] Univ Turin, Dept Oncol, Turin, Italy. [Smyth, Mark J.] QIMR Berghofer Med Res Inst, Immunol Canc & Infect Lab, Herston, Qld, Australia. [Smyth, Mark J.] Univ Queensland, Sch Med, Herston, Qld, Australia. [Sonnemann, Juergen] Jena Univ Hosp, Childrens Clin, Dept Paediat Haematol & Oncol, Jena, Germany. [Stagg, John] Univ Montreal, Fac Pharm, Inst Canc Montreal, Ctr Rech,Ctr Hosp Univ Montreal, Montreal, PQ, Canada. [Vandenberk, Lien; Van Gool, Stefaan] Univ Leuven, KU Leuven, Dept Microbiol & Immunol, Lab Pediat Immunol, Leuven, Belgium. [Van den Eynde, Benoit J.] Catholic Univ Louvain, Ludwig Inst Canc Res, Duve Inst, B-1200 Brussels, Belgium. [Velotti, Francesca] Univ Tuscia, Dept Ecol & Biol Sci, Viterbo, Italy. [Zitvogel, Laurence] Univ Paris Sud, F-94275 Le Kremlin Bicetre, France. [Zitvogel, Laurence] INSERM, U1015, Villejuif, France. [Zitvogel, Laurence] Ctr Clin Invest Biotherapies Canc CICBT 507, Villejuif, France. RP Garg, AD (reprint author), Univ Leuven, KU Leuven, Dept Cellular Mol Med, Cell Death Res & Therapy, Leuven, Belgium. EM abhishek.garg@med.kuleuven.be; patrizia.agostinis@med.kuleuven.be RI Garg, Abhishek/D-5230-2012; Golab, Jakub/K-6974-2013; Vandenabeele, Peter/C-8597-2009; Maueroder, Christian/H-7412-2016; Krysko, Dmitri/G-9500-2013; Ricci, Jean Ehrland/I-7117-2016; herrmann, martin/A-9597-2013; Apetoh, Lionel/G-3310-2014; Hodge, James/D-5518-2015; OI Garg, Abhishek/0000-0002-9976-9922; Golab, Jakub/0000-0002-2830-5100; Maueroder, Christian/0000-0002-7563-883X; Krysko, Dmitri/0000-0002-9692-2047; Ricci, Jean Ehrland/0000-0003-1585-8117; herrmann, martin/0000-0002-0258-2484; Apetoh, Lionel/0000-0002-2774-438X; Hodge, James/0000-0001-5282-3154; Land, Walter/0000-0002-0090-0629; Bravo-San Pedro, Jose Manuel/0000-0002-5781-1133 FU Fund for Scientific Research Flanders (FWO-Vlaanderen) [G.0661.09, G.0728.10, G.0584.12N]; KU Leuven [GOA/11/009]; Inter university Attraction Poles Programme; Belgian State, Science Policy Office FX We would like to explicitly declare that this manuscript does not aim to describe guidelines for the fields of ICD and DAMP research. Rather, it is meant to be a comprehensive classification and review of relevant literature expressing consensus discussions, opinions, and conclusions endorsed and/or supported by a number of researchers and clinicians investigating ICI) and DAM Ps. We would also like to acknowledge the following colleagues for their support, reading and/or positive appraisal of this manuscript: Wee Han Ang, Vincenzo Barnaba, Marco E. Bianchi, Kariti de Visser, Sandra 0. Gollnick, Peter Henson, Polly Niatzinger, Niarek Michalak, Kodi Ravichandran, and Andrew Thorburn. ADC is a recipient of the FWO postdoctoral fellowship 2013. This work was supported by grants from the Fund for Scientific Research Flanders (FWO-Vlaanderen; (G.0661.09, G.0728.10 and G.0584.12N) and KU Leuven (GOA/11/009) to PA; This paper presents research results of the IAP7/32, funded by the Inter university Attraction Poles Programme, initiated by the Belgian State, Science Policy Office. NR 246 TC 26 Z9 26 U1 5 U2 27 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PD NOV 20 PY 2015 VL 6 AR UNSP 588 DI 10.3389/fimmu.2015.00588 PG 24 WC Immunology SC Immunology GA CY0TW UT WOS:000366120100002 PM 26635802 ER PT J AU Chen, LJ Hambright, WS Na, R Ran, QT AF Chen, Liuji Hambright, William Sealy Na, Ren Ran, Qitao TI Ablation of the Ferroptosis Inhibitor Glutathione Peroxidase 4 in Neurons Results in Rapid Motor Neuron Degeneration and Paralysis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; NONAPOPTOTIC CELL-DEATH; TRANSGENIC MICE; OXIDATIVE DAMAGE; APOPTOSIS; GPX4; GENERATION; PROTECTS; PHGPX AB Glutathione peroxidase 4 (GPX4), an antioxidant defense enzyme active in repairing oxidative damage to lipids, is a key inhibitor of ferroptosis, a non-apoptotic form of cell death involving lipid reactive oxygen species. Here we show that GPX4 is essential for motor neuron health and survival in vivo. Conditional ablation of Gpx4 in neurons of adult mice resulted in rapid onset and progression of paralysis and death. Pathological inspection revealed that the paralyzed mice had a dramatic degeneration of motor neurons in the spinal cord but had no overt neuron degeneration in the cerebral cortex. Consistent with the role of GPX4 as a ferroptosis inhibitor, spinal motor neuron degeneration induced by Gpx4 ablation exhibited features of ferroptosis, including no caspase-3 activation, no TUNEL staining, activation of ERKs, and elevated spinal inflammation. Supplementation with vitamin E, another inhibitor of ferroptosis, delayed the onset of paralysis and death induced by Gpx4 ablation. Also, lipid peroxidation and mitochondrial dysfunction appeared to be involved in ferroptosis of motor neurons induced by Gpx4 ablation. Taken together, the dramatic motor neuron degeneration and paralysis induced by Gpx4 ablation suggest that ferroptosis inhibition by GPX4 is essential for motor neuron health and survival in vivo. C1 [Chen, Liuji; Hambright, William Sealy; Na, Ren; Ran, Qitao] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Ran, Qitao] South Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX 78229 USA. RP Ran, QT (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM ran@uthscsa.edu FU Department of Veterans Affairs; Alzheimer's Association; William and Ella Owens Medical Research Foundation FX Supported by a merit review grant from the Department of Veterans Affairs, a grant from the Alzheimer's Association, and an award from The William and Ella Owens Medical Research Foundation. To whom correspondence should be addressed: Dept. of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229. Tel.: 210-567-3842; Fax: 210-567-6781; E-mail: ran@uthscsa.edu. NR 23 TC 11 Z9 11 U1 4 U2 20 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 20 PY 2015 VL 290 IS 47 BP 28097 EP 28106 DI 10.1074/jbc.M115.680090 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA CX5SD UT WOS:000365761900006 PM 26400084 ER PT J AU Solin, LJ Gray, R Hughes, LL Wood, WC Lowen, MA Badve, SS Baehner, FL Ingle, JN Perez, EA Recht, A Sparano, JA Davidson, NE AF Solin, Lawrence J. Gray, Robert Hughes, Lorie L. Wood, William C. Lowen, Mary Ann Badve, Sunil S. Baehner, Frederick L. Ingle, James N. Perez, Edith A. Recht, Abram Sparano, Joseph A. Davidson, Nancy E. TI Surgical Excision Without Radiation for Ductal Carcinoma in Situ of the Breast: 12-Year Results From the ECOG-ACRIN E5194 Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CONSERVING SURGERY; ADJUVANT BREAST; EUROPEAN ORGANIZATION; RECURRENCE RISK; RADIOTHERAPY; CANCER; TRIAL; DCIS; PROJECT; EXPRESSION AB Purpose To determine the 12-year risk of developing an ipsilateral breast event (IBE) for women with ductal carcinoma in situ (DCIS) of the breast treated with surgical excision (lumpectomy) without radiation. Patients and Methods A prospective clinical trial was performed for women with DCIS who were selected for low-risk clinical and pathologic characteristics. Patients were enrolled onto one of two study cohorts (not randomly assigned): cohort 1: low- or intermediate-grade DCIS, tumor size 2.5 cm or smaller (n = 561); or cohort 2: high-grade DCIS, tumor size 1 cm or smaller (n = 104). Protocol specifications included excision of the DCIS tumor with a minimum negative margin width of at least 3 mm. Tamoxifen (not randomly assigned) was given to 30% of the patients. An IBE was defined as local recurrence of DCIS or invasive carcinoma in the treated breast. Median follow-up time was 12.3 years. Results There were 99 IBEs, of which 51 (52%) were invasive. The IBE and invasive IBE rates increased over time in both cohorts. The 12-year rates of developing an IBE were 14.4% for cohort 1 and 24.6% for cohort 2 (P = .003). The 12-year rates of developing an invasive IBE were 7.5% and 13.4%, respectively (P = .08). On multivariable analysis, study cohort and tumor size were both significantly associated with developing an IBE (P = .009 and P = .03, respectively). Conclusion For patients with DCIS selected for favorable clinical and pathologic characteristics and treated with excision without radiation, the risks of developing an IBE and an invasive IBE increased through 12 years of follow-up, without plateau. These data help inform the treatment decision-making process for patients and their physicians. (C) 2015 by American Society of Clinical Oncology C1 [Solin, Lawrence J.] Albert Einstein Healthcare Network, Philadelphia, PA 19141 USA. [Davidson, Nancy E.] Univ Pittsburgh, Pittsburgh, PA USA. [Gray, Robert] Dana Farber Canc Inst, Boston, MA USA. [Recht, Abram] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Recht, Abram] Harvard Univ, Sch Med, Boston, MA USA. [Lowen, Mary Ann] Baystate Med Ctr, Springfield, MA USA. [Hughes, Lorie L.] Gordon Hosp, Harris Radiat Therapy Ctr, Calhoun, GA USA. [Wood, William C.] Emory Univ, Atlanta, GA 30322 USA. [Badve, Sunil S.] Indiana Univ, Indianapolis, IN 46204 USA. [Baehner, Frederick L.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Ingle, James N.] Mayo Clin, Rochester, MN USA. [Perez, Edith A.] Mayo Clin, Jacksonville, FL 32224 USA. [Sparano, Joseph A.] Montefiore Med Ctr, Bronx, NY 10467 USA. RP Solin, LJ (reprint author), Albert Einstein Healthcare Network, Dept Radiat Oncol, 5501 Old York Rd, Philadelphia, PA 19141 USA. EM solin@einstein.edu FU Public Health Service Grants from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services [CA180820, CA180794, CA189859, CA180864, CA180795, CA180844, CA180802, CA25224]; Breast Cancer Research Foundation FX Supported in part by Public Health Service Grants No. CA180820, CA180794, CA189859, CA180864, CA180795, CA180844, CA180802, CA25224 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, and by the Breast Cancer Research Foundation. NR 32 TC 31 Z9 31 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 20 PY 2015 VL 33 IS 33 BP 3938 EP + DI 10.1200/JCO.2015.60.8588 PG 12 WC Oncology SC Oncology GA CX9JB UT WOS:000366020600017 PM 26371148 ER PT J AU Stein, BL Oh, ST Berenzon, D Hobbs, GS Kremyanskaya, M Rampal, RK Abboud, CN Adler, K Heaney, ML Jabbour, EJ Komrokji, RS Moliterno, AR Ritchie, EK Rice, L Mascarenhas, J Hoffman, R AF Stein, Brady L. Oh, Stephen T. Berenzon, Dmitriy Hobbs, Gabriela S. Kremyanskaya, Marina Rampal, Raajit K. Abboud, Camille N. Adler, Kenneth Heaney, Mark L. Jabbour, Elias J. Komrokji, Rami S. Moliterno, Alison R. Ritchie, Ellen K. Rice, Lawrence Mascarenhas, John Hoffman, Ronald TI Polycythemia Vera: An Appraisal of the Biology and Management 10 Years After the Discovery of JAK2 V617F SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID JAK2V617F ALLELE BURDEN; ORGANIZATION DIAGNOSTIC-CRITERIA; JAK2 EXON-12 MUTATIONS; TYROSINE KINASE JAK2; QUALITY-OF-LIFE; RED-CELL MASS; ESSENTIAL THROMBOCYTHEMIA; MYELOPROLIFERATIVE NEOPLASMS; HIGH-RISK; LEUKEMIC TRANSFORMATION AB Polycythemia vera (PV) is a chronic myeloproliferative neoplasm that is associated with a substantial symptom burden, thrombohemorrhagic complications, and impaired survival. A decade after the seminal discovery of an activating mutation in the tyrosine kinase JAK2 in nearly all patients with PV, new treatment options are finally beginning to emerge, necessitating a critical reappraisal of the underlying pathogenesis and therapeutic modalities available for PV. Herein, we comprehensively review clinical aspects of PV including diagnostic considerations, natural history, and risk factors for thrombosis. We summarize recent studies delineating the genetic basis of PV, including their implications for evolution to myelofibrosis and secondary acute myeloid leukemia. We assess the quality of evidence to support the use of currently available therapies, including aspirin, phlebotomy, hydroxyurea, and interferon. We analyze recent studies evaluating the safety and efficacy of JAK inhibitors, such as ruxolitinib, and evaluate their role in the context of other available therapies for PV. This review provides a framework for practicing hematologists and oncologists to make rational treatment decisions for patients with PV. (C) 2015 by American Society of Clinical Oncology C1 [Stein, Brady L.] Northwestern Feinberg Univ, Sch Med, Chicago, IL USA. [Oh, Stephen T.; Abboud, Camille N.] Washington Univ, Sch Med, St Louis, MO USA. [Berenzon, Dmitriy] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. [Hobbs, Gabriela S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kremyanskaya, Marina; Mascarenhas, John; Hoffman, Ronald] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Rampal, Raajit K.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Heaney, Mark L.] Columbia Univ, Med Ctr, New York, NY 10027 USA. [Ritchie, Ellen K.] Cornell Univ, Sch Med, New York, NY 10021 USA. [Adler, Kenneth] Reg Canc Care Associates, Morristown, NJ USA. [Jabbour, Elias J.] MD Anderson Canc Ctr, Houston, TX USA. [Rice, Lawrence] Cornell Houston Methodist Hosp, Houston, TX USA. [Komrokji, Rami S.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Moliterno, Alison R.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Hoffman, R (reprint author), Icahn Sch Med Mt Sinai, Tisch Canc Inst, One Gustave L Levy Pl,Box 1079, New York, NY 10029 USA. EM ronald.hoffman@mssm.edu OI Hobbs, Gabriela/0000-0002-0199-9333 FU Incyte; Gilead; CTI Biopharma; Pfizer; Merck; Novartis; Sanofi/Genzyme; Cellerant Therapeutics; Celgene; Geron; Roche FX Incyte (Inst), Gilead (Inst), CTI Biopharma (Inst); Incyte; Pfizer (Inst), Merck (Inst), Novartis (Inst), Sanofi/Genzyme (Inst), CTI Biopharma (Inst), Cellerant Therapeutics (Inst); Incyte (Inst), Celgene (Inst); Geron, Incyte, Novartis, Roche NR 84 TC 8 Z9 8 U1 3 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 20 PY 2015 VL 33 IS 33 BP 3953 EP + DI 10.1200/JCO.2015.61.6474 PG 9 WC Oncology SC Oncology GA CX9JB UT WOS:000366020600019 PM 26324368 ER PT J AU Ligibel, JA Alfano, CM Hershman, D Ballard, RM Bruinooge, SS Courneya, KS Daniels, EC Demark-Wahnefried, W Frank, ES Goodwin, PJ Irwin, ML Levit, LA McCaskill-Stevens, W Minasian, LM O'Rourke, MA Pierce, JP Stein, KD Thomson, CA Hudis, CA AF Ligibel, Jennifer A. Alfano, Catherine M. Hershman, Dawn Ballard, Rachel M. Bruinooge, Suanna S. Courneya, Kerry S. Daniels, Elvan C. Demark-Wahnefried, Wendy Frank, Elizabeth S. Goodwin, Pamela J. Irwin, Melinda L. Levit, Laura A. McCaskill-Stevens, Worta Minasian, Lori M. O'Rourke, Mark A. Pierce, John P. Stein, Kevin D. Thomson, Cynthia A. Hudis, Clifford A. TI Recommendations for Obesity Clinical Trials in Cancer Survivors: American Society of Clinical Oncology Statement SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BODY-MASS INDEX; PHYSICAL-ACTIVITY; PROSTATE-CANCER; RANDOMIZED-TRIAL; BREAST; INTERVENTION; METAANALYSIS; WEIGHT; DIET; RECURRENCE C1 [Ligibel, Jennifer A.; Frank, Elizabeth S.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Alfano, Catherine M.; Daniels, Elvan C.; Stein, Kevin D.] Amer Canc Soc, Atlanta, GA 30329 USA. [Hershman, Dawn] Columbia Univ, New York, NY 10027 USA. [Hudis, Clifford A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Ballard, Rachel M.] NIH, Bethesda, MD USA. [McCaskill-Stevens, Worta; Minasian, Lori M.] NCI, Bethesda, MD 20892 USA. [Bruinooge, Suanna S.; Levit, Laura A.] Amer Soc Clin Oncol, Alexandria, VA USA. [Courneya, Kerry S.] Univ Alberta, Edmonton, AB, Canada. [Goodwin, Pamela J.] Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. [Demark-Wahnefried, Wendy] Univ Alabama Birmingham, Birmingham, AL USA. [Irwin, Melinda L.] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [O'Rourke, Mark A.] Greenville Hosp Syst, Greenville, SC USA. [Pierce, John P.] Univ Calif San Diego, Moores Canc Ctr, San Diego, CA 92103 USA. [Thomson, Cynthia A.] Univ Arizona, Tucson, AZ USA. RP Ligibel, JA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM jligibel@partners.org RI Goodwin, Pamela/K-1477-2013 FU NCI NIH HHS [P30 CA008748] NR 38 TC 12 Z9 12 U1 2 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 20 PY 2015 VL 33 IS 33 BP 3961 EP + DI 10.1200/JCO.2015.63.1440 PG 9 WC Oncology SC Oncology GA CX9JB UT WOS:000366020600020 PM 26324364 ER PT J AU Wiener, L Feudtner, C Hinds, P Wolfe, J Mack, J AF Wiener, Lori Feudtner, Chris Hinds, Pamela Wolfe, Joanne Mack, Jennifer TI Deeper Conversations Need Not Wait Until the End SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID OF-LIFE CARE; YOUNG-ADULTS; ADOLESCENTS; DISCUSSIONS; CHILDREN; CANCER C1 [Wiener, Lori] NCI, Bethesda, MD 20892 USA. [Feudtner, Chris] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Hinds, Pamela] Childrens Natl Hlth Syst, Washington, DC USA. [Hinds, Pamela] George Washington Univ, Washington, DC USA. [Wolfe, Joanne; Mack, Jennifer] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wolfe, Joanne; Mack, Jennifer] Boston Childrens Hosp, Boston, MA USA. RP Wiener, L (reprint author), NCI, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 CA999999] NR 10 TC 1 Z9 1 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 20 PY 2015 VL 33 IS 33 BP 3974 EP + DI 10.1200/JCO.2015.62.3405 PG 2 WC Oncology SC Oncology GA CX9JB UT WOS:000366020600023 PM 26282649 ER PT J AU Li, RS Jen, N Wu, L Lee, J Fang, K Quigley, K Lee, K Wang, S Zhou, B Vergnes, L Chen, YR Li, ZP Reue, K Ann, DK Hsiai, TK AF Li, Rongsong Jen, Nelson Wu, Lan Lee, Juhyun Fang, Karen Quigley, Katherine Lee, Katherine Wang, Sky Zhou, Bill Vergnes, Laurent Chen, Yun-Ru Li, Zhaoping Reue, Karen Ann, David K. Hsiai, Tzung K. TI Disturbed Flow Induces Autophagy, but Impairs Autophagic Flux to Perturb Mitochondrial Homeostasis SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID WALL SHEAR-STRESS; OXIDATIVE STRESS; DNA-DAMAGE; ENDOTHELIAL FUNCTION; NADPH OXIDASE; MN-SOD; ATHEROSCLEROSIS; CELLS; DISEASE; PROTEINS AB Aim: Temporal and spatial variations in shear stress are intimately linked with vascular metabolic effects. Autophagy is tightly regulated in intracellular bulk degradation/recycling system for maintaining cellular homeostasis. We postulated that disturbed flow modulates autophagy with an implication in mitochondrial superoxide (mtO(2)(center dot-)) production. Results: In the disturbed flow or oscillatory shear stress (OSS)-exposed aortic arch, we observed prominent staining of p62, a reverse marker of autophagic flux, whereas in the pulsatile shear stress (PSS)-exposed descending aorta, p62 was attenuated. OSS significantly increased (i) microtubule-associated protein light chain 3 (LC3) II to I ratios in human aortic endothelial cells, (ii) autophagosome formation as quantified by green fluorescent protein (GFP)-LC3 dots per cell, and (iii) p62 protein levels, whereas manganese superoxide dismutase (MnSOD) overexpression by recombinant adenovirus, N-acetyl cysteine treatment, or c-Jun N-terminal kinase (JNK) inhibition reduced OSS-mediated LC3-II/LC3-I ratios and mitochondrial DNA damage. Introducing bafilomycin to Earle's balanced salt solution or to OSS condition incrementally increased both LC3-II/LC3-I ratios and p62 levels, implicating impaired autophagic flux. In the OSS-exposed aortic arch, both anti-phospho-JNK and anti-8-hydroxy-2-deoxyguanosine (8-OHdG) staining for DNA damage were prominent, whereas in the PSS-exposed descending aorta, the staining was nearly absent. Knockdown of ATG5 with siRNA increased OSS-mediated mtO(2)(center dot-), whereas starvation or rapamycin-induced autophagy reduced OSS-mediated mtO(2)(center dot-), mitochondrial respiration, and complex II activity. Innovation: Disturbed flow-mediated oxidative stress and JNK activation induce autophagy. Conclusion: OSS impairs autophagic flux to interfere with mitochondrial homeostasis. Antioxid. Redox Signal. 23, 1207-1219. C1 [Li, Rongsong; Wu, Lan; Fang, Karen; Quigley, Katherine; Lee, Katherine; Wang, Sky; Zhou, Bill; Hsiai, Tzung K.] Univ Calif Los Angeles, David Geffen Sch Med, Div Cardiol, Dept Med, Los Angeles, CA 90095 USA. [Jen, Nelson; Lee, Juhyun; Hsiai, Tzung K.] Univ Calif Los Angeles, Dept Bioengn, Henry Samueli Sch Engn & Appl Sci, Los Angeles, CA 90095 USA. [Vergnes, Laurent; Reue, Karen] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. [Chen, Yun-Ru; Ann, David K.] City Hope Natl Med Ctr, Beckman Res Inst, Dept Mol Pharmacol, Duarte, CA 91010 USA. [Li, Zhaoping; Hsiai, Tzung K.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90095 USA. RP Hsiai, TK (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Henry Samueli Sch Engn & Appl Sci, Dept Med Cardiol, Los Angeles, CA 90095 USA. EM thsiai@mednet.ucla.edu FU National Institutes of Health [HL083015, HL118650, HL111437, DE010742, DE014183] FX The authors are grateful to Dr. Junichi Sadoshima from Rutgers New Jersey Medical School for providing recombinant GFP-LC3 adenoviruses. The authors thank Dr. Peixiang Zhang from UCLA for the Seahorse assay. This project was supported by National Institutes of Health, HL083015 (T.K.H.), HL118650 (T.K.H.), HL111437 (T.K.H.), DE010742 (D.K.A.), and DE014183 (D.K.A.). NR 79 TC 6 Z9 6 U1 2 U2 11 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD NOV 20 PY 2015 VL 23 IS 15 BP 1207 EP 1219 DI 10.1089/ars.2014.5896 PG 13 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA CX2HJ UT WOS:000365517400001 PM 26120766 ER PT J AU Joung, JK Voytas, DF Kamens, J AF Joung, J. Keith Voytas, Daniel F. Kamens, Joanne TI Accelerating research through reagent repositories: the genome editing example SO GENOME BIOLOGY LA English DT Editorial Material AB Keith Joung, Dan Voytas and Joanne Kamens share insights into how the genome editing field was advanced by early access to biological resources and the role in this process that plasmid repositories play. C1 [Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Mol Pathol Unit, Charlestown, MA 02129 USA. [Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. [Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Voytas, Daniel F.] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. [Voytas, Daniel F.] Univ Minnesota, Ctr Genome Engn, Minneapolis, MN 55455 USA. [Kamens, Joanne] Addgene, Cambridge, MA 02139 USA. RP Joung, JK (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Mol Pathol Unit, Charlestown, MA 02129 USA. EM jjoung@mgh.harvard.edu; voytas@umn.edu; joanne.kamens@addgene.org NR 0 TC 3 Z9 3 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-6906 EI 1474-760X J9 GENOME BIOL JI Genome Biol. PD NOV 20 PY 2015 VL 16 AR 255 DI 10.1186/s13059-015-0830-y PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA CX3BG UT WOS:000365569900001 PM 26585970 ER PT J AU Tedesco, P Visone, M Parrilli, E Tutino, ML Perrin, E Maida, I Fani, R Ballestriero, F Santos, R Pinilla, C Di Schiavi, E Tegos, G de Pascale, D AF Tedesco, Pietro Visone, Marco Parrilli, Ermenegilda Tutino, Maria Luisa Perrin, Elena Maida, Isabel Fani, Renato Ballestriero, Francesco Santos, Radleigh Pinilla, Clemencia Di Schiavi, Elia Tegos, George de Pascale, Donatella TI Investigating the Role of the Host Multidrug Resistance Associated Protein Transporter Family in Burkholderia cepacia Complex Pathogenicity Using a Caenorhabditis elegans Infection Model SO PLOS ONE LA English DT Article ID CYSTIC-FIBROSIS; VIRULENCE FACTORS; IVERMECTIN RESISTANCE; CENOCEPACIA STRAINS; PSEUDOMALLEI KILLS; FULL VIRULENCE; SP NOV.; EFFLUX; IDENTIFICATION; DIVERSITY AB This study investigated the relationship between host efflux system of the non-vertebrate nematode Caenorhabditis elegans and Burkholderia cepacia complex (Bcc) strain virulence. This is the first comprehensive effort to profile host-transporters within the context of Bcc infection. With this aim, two different toxicity tests were performed: a slow killing assay that monitors mortality of the host by intestinal colonization and a fast killing assay that assesses production of toxins. A Virulence Ranking scheme was defined, that expressed the toxicity of the Bcc panel members, based on the percentage of surviving worms. According to this ranking the 18 Bcc strains were divided in 4 distinct groups. Only the Cystic Fibrosis isolated strains possessed profound nematode killing ability to accumulate in worms' intestines. For the transporter analysis a complete set of isogenic nematode single Multidrug Resistance associated Protein (MRP) efflux mutants and a number of efflux inhibitors were interrogated in the host toxicity assays. The Bcc pathogenicity profile of the 7 isogenic C. elegans MRP knock-out strains functionality was classified in two distinct groups. Disabling host transporters enhanced nematode mortality more than 50% in 5 out of 7 mutants when compared to wild type. In particular mrp-2 was the most susceptible phenotype with increased mortality for 13 out 18 Bcc strains, whereas mrp-3 and mrp-4 knockouts had lower mortality rates, suggesting a different role in toxin-substrate recognition. The use of MRP efflux inhibitors in the assays resulted in substantially increased (>40% on average) mortality of wild-type worms. C1 [Tedesco, Pietro; Visone, Marco; de Pascale, Donatella] CNR, Inst Prot Biochem, I-80131 Naples, Italy. [Tedesco, Pietro; Parrilli, Ermenegilda; Tutino, Maria Luisa] Univ Naples Federico II, Dept Chem Sci, I-80126 Naples, Italy. [Tedesco, Pietro; Parrilli, Ermenegilda; Tutino, Maria Luisa] Univ Naples Federico II, Sch Biotechnol Sci, I-80126 Naples, Italy. [Perrin, Elena; Maida, Isabel; Fani, Renato] Univ Florence, Dept Biol, Lab Microbial & Mol Evolut, I-50019 Florence, Italy. [Ballestriero, Francesco] Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW 2052, Australia. [Ballestriero, Francesco] Univ New S Wales, Ctr Marine Bioinnovat, Sydney, NSW 2052, Australia. [Santos, Radleigh; Pinilla, Clemencia; Tegos, George] Torrey Pines Inst Mol Studies, Port St Lucie, FL 34987 USA. [Santos, Radleigh; Pinilla, Clemencia; Tegos, George] Torrey Pines Inst Mol Studies, San Diego, CA USA. [Di Schiavi, Elia] CNR, Inst Biosci & BioResources, I-80131 Naples, Italy. [Di Schiavi, Elia] CNR, Inst Genet & Biophys, I-80131 Naples, Italy. [Tegos, George] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tegos, George] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Tegos, G (reprint author), Torrey Pines Inst Mol Studies, Port St Lucie, FL 34987 USA. EM gtegos@tpims.org; d.depascale@ibp.cnr.it RI parrilli, ermenegilda/K-4616-2016; Di Schiavi, Elia/B-8046-2015; OI parrilli, ermenegilda/0000-0002-9002-5409; Di Schiavi, Elia/0000-0002-8179-6666; Tutino, Maria Luisa/0000-0002-4978-6839 FU EU-KBBE project PharmaSea [312184]; "Fondazione Adriano Buzzati-Traverso" fellowship FX Funding: This work was supported by the EU-KBBE 2012-2016 project PharmaSea, grant No 312184. Elena Perrin is financially supported by a "Fondazione Adriano Buzzati-Traverso" fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 58 TC 0 Z9 0 U1 4 U2 21 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 20 PY 2015 VL 10 IS 11 AR e0142883 DI 10.1371/journal.pone.0142883 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW8LQ UT WOS:000365251500020 PM 26587842 ER PT J AU Sigova, AA Abraham, BJ Ji, X Molinie, B Hannett, NM Guo, YE Jangi, M Giallourakis, CC Sharp, PA Young, RA AF Sigova, Alla A. Abraham, Brian J. Ji, Xiong Molinie, Benoit Hannett, Nancy M. Guo, Yang Eric Jangi, Mohini Giallourakis, Cosmas C. Sharp, Phillip A. Young, Richard A. TI Transcription factor trapping by RNA in gene regulatory elements SO SCIENCE LA English DT Article ID DIVERGENT TRANSCRIPTION; SUPER-ENHANCERS; HUMAN PROMOTERS; CELL IDENTITY; EXOSOME; YY1; DNA; ACTIVATION; MEDIATOR; DISEASE AB Transcription factors (TFs) bind specific sequences in promoter-proximal and -distal DNA elements to regulate gene transcription. RNA is transcribed from both of these DNA elements, and some DNA binding TFs bind RNA. Hence, RNA transcribed from regulatory elements may contribute to stable TF occupancy at these sites. We show that the ubiquitously expressed TF Yin-Yang 1 (YY1) binds to both gene regulatory elements and their associated RNA species across the entire genome. Reduced transcription of regulatory elements diminishes YY1 occupancy, whereas artificial tethering of RNA enhances YY1 occupancy at these elements. We propose that RNA makes a modest but important contribution to the maintenance of certain TFs at gene regulatory elements and suggest that transcription of regulatory elements produces a positive-feedback loop that contributes to the stability of gene expression programs. C1 [Sigova, Alla A.; Abraham, Brian J.; Ji, Xiong; Hannett, Nancy M.; Guo, Yang Eric; Young, Richard A.] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. [Molinie, Benoit; Giallourakis, Cosmas C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jangi, Mohini; Sharp, Phillip A.; Young, Richard A.] MIT, Dept Biol, Cambridge, MA 02142 USA. [Jangi, Mohini; Sharp, Phillip A.] David H Koch Inst Integrat Canc Res, Cambridge, MA 02140 USA. RP Young, RA (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM young@wi.mit.edu RI Young, Richard/F-6495-2012 OI Young, Richard/0000-0001-8855-8647 FU NIH [HG002668]; Hope Funds for Cancer Research; Cancer Research Institute; Biogen FX We thank D. Orlando, C. Lin, V. Saint-Andre, Z. P. Fan, L. Zhang, and A. Chiu for help with computational analysis and advice. The lentiviral dCas9 and sgRNA expression plasmids are available from Addgene under the Uniform Biological Material Transfer Agreement. This work was supported by NIH grant HG002668 (R.A.Y.), the Hope Funds for Cancer Research (B.J.A.), the Cancer Research Institute (Y.E.G), and Biogen (R.A.Y.). The Whitehead Institute intends to file a patent application that relates to transcription factor trapping by RNA. R.A.Y. is a founder of Syros Pharmaceuticals. NR 24 TC 43 Z9 44 U1 5 U2 42 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD NOV 20 PY 2015 VL 350 IS 6263 BP 978 EP 981 DI 10.1126/science.aad3346 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW4IP UT WOS:000364955200049 PM 26516199 ER PT J AU Doshi, BN Fu, J Oral, E Muratoglu, OK AF Doshi, Brinda N. Fu, Jun Oral, Ebru Muratoglu, Orhun K. TI Vitamin E can be used to hinder scissioning in radiation cross-linked UHMWPE during high-temperature melting SO JOURNAL OF APPLIED POLYMER SCIENCE LA English DT Article DE biomedical applications; irradiation; mechanical properties; morphology; polyolefins ID MOLECULAR-WEIGHT POLYETHYLENE; TOTAL HIP-ARTHROPLASTY; IN-VIVO OXIDATION; MECHANICAL-PROPERTIES; DENSITY POLYETHYLENE; ALPHA-TOCOPHEROL; RESISTANT UHMWPE; FREE-RADICALS; LOW WEAR; LINKING AB High-temperature melting (HTM) of ultrahigh molecular weight polyethylene (UHMWPE) was shown to improve its elongation and toughness. This was believed to be due to increased scissioning and increased diffusion of polymer chains. It was hypothesized here that the toughness of previously radiation cross-linked UHMWPEs could also be improved by HTM. To test this hypothesis, the wear resistance, tensile mechanical properties, and Izod impact strength of radiation cross-linked virgin (no additive) and antioxidant-blended (with vitamin E) UHMWPEs were tested. The results suggested that although the impact strength of cross-linked UHMWPEs could be improved significantly by HTM, the wear resistance was decreased. Thus, this procedure can be optimized to be especially suited in high-stress applications, such as total knee replacements with lessened wear concerns. (c) 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42735. C1 [Doshi, Brinda N.; Fu, Jun; Oral, Ebru; Muratoglu, Orhun K.] Massachusetts Gen Hosp, Harris Orthoped Lab, Boston, MA 02114 USA. [Fu, Jun; Oral, Ebru; Muratoglu, Orhun K.] Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Oral, E (reprint author), Massachusetts Gen Hosp, Harris Orthoped Lab, Boston, MA 02114 USA. EM eoral@partners.org FU Harris Orthopedic Laboratory FX This study was funded by the Harris Orthopedic Laboratory. NR 38 TC 3 Z9 3 U1 4 U2 44 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-8995 EI 1097-4628 J9 J APPL POLYM SCI JI J. Appl. Polym. Sci. PD NOV 20 PY 2015 VL 132 IS 44 AR 42735 DI 10.1002/app.42735 PG 8 WC Polymer Science SC Polymer Science GA CP9NO UT WOS:000360221300015 ER PT J AU Balsa-Martinez, E Puigserver, P AF Balsa-Martinez, Eduardo Puigserver, Pere TI Cancer Cells Hijack Gluconeogenic Enzymes to Fuel Cell Growth SO MOLECULAR CELL LA English DT Editorial Material ID PHOSPHOENOLPYRUVATE CARBOXYKINASE AB In this issue and the October 15th issue of Molecular Cell, studies by Montal et al. (2015) and Vincent et al. (2015) report that certain types of cancer cells utilize the gluconeogenic enzymes phosphoenolpyruvate carboxykinase (PEPCK) and phosphoenolpyruvate carboxykinase 2 (PCK2) to reprogram anabolic metabolism and support cell growth. C1 [Balsa-Martinez, Eduardo; Puigserver, Pere] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Balsa-Martinez, Eduardo; Puigserver, Pere] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Puigserver, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM pere_puigserver@dfci.harvard.edu NR 8 TC 3 Z9 4 U1 5 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 EI 1097-4164 J9 MOL CELL JI Mol. Cell PD NOV 19 PY 2015 VL 60 IS 4 BP 509 EP 511 DI 10.1016/j.molcel.2015.11.005 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DB1SH UT WOS:000368288700001 PM 26590709 ER PT J AU Lau, AN Vander Heiden, MG AF Lau, Allison N. Vander Heiden, Matthew G. TI Stopping the Clock with MYC SO MOLECULAR CELL LA English DT Editorial Material ID CANCER; METABOLISM AB In a recent paper in Cell Metabolism, Altman et al. (2015) report that MYC disrupts the molecular clock in cancer cells and describe a link between oncogenesis, circadian rhythms, and metabolism. C1 [Lau, Allison N.; Vander Heiden, Matthew G.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Vander Heiden, Matthew G.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Vander Heiden, MG (reprint author), MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM mvh@mit.edu NR 10 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 EI 1097-4164 J9 MOL CELL JI Mol. Cell PD NOV 19 PY 2015 VL 60 IS 4 BP 511 EP 513 DI 10.1016/j.molcel.2015.11.008 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DB1SH UT WOS:000368288700002 PM 26590710 ER PT J AU Montal, ED Dewi, R Bhalla, K Ou, LH Hwang, BJ Ropell, AE Gordon, C Liu, WJ DeBerardinis, RJ Sudderth, J Twaddel, W Boros, LG Shroyer, KR Duraisamy, S Drapkin, R Powers, RS Rohde, JM Boxer, MB Wong, KK Girnun, GD AF Montal, Emily D. Dewi, Ruby Bhalla, Kavita Ou, Lihui Hwang, Bor Jang Ropell, Ashley E. Gordon, Chris Liu, Wan-Ju DeBerardinis, Ralph J. Sudderth, Jessica Twaddel, William Boros, Laszlo G. Shroyer, Kenneth R. Duraisamy, Sekhar Drapkin, Ronny Powers, R. Scott Rohde, Jason M. Boxer, Matthew B. Wong, Kwok-Kin Girnun, Geoffrey D. TI PEPCK Coordinates the Regulation of Central Carbon Metabolism to Promote Cancer Cell Growth SO MOLECULAR CELL LA English DT Article ID CYTOSOLIC PHOSPHOENOLPYRUVATE CARBOXYKINASE; GLUTAMINE-METABOLISM; AEROBIC GLYCOLYSIS; COPY NUMBER; AMINO-ACID; GLUCOSE; MTORC1; PROLIFERATION; SURVIVAL; TUMORS AB Phosphoenolpyruvate carboxykinase (PEPCK) is well known for its role in gluconeogenesis. However, PEPCK is also a key regulator of TCA cycle flux. The TCA cycle integrates glucose, amino acid, and lipid metabolism depending on cellular needs. In addition, biosynthetic pathways crucial to tumor growth require the TCA cycle for the processing of glucose and glutamine derived carbons. We show here an unexpected role for PEPCK in promoting cancer cell proliferation in vitro and in vivo by increasing glucose and glutamine utilization toward anabolic metabolism. Unexpectedly, PEPCK also increased the synthesis of ribose from non-carbohydrate sources, such as glutamine, a phenomenon not previously described. Finally, we show that the effects of PEPCK on glucose metabolism and cell proliferation are in part mediated via activation of mTORC1. Taken together, these data demonstrate a role for PEPCK that links metabolic flux and anabolic pathways to cancer cell proliferation. C1 [Montal, Emily D.; Girnun, Geoffrey D.] SUNY Stony Brook, Dept Pharmacol Sci, Stony Brook, NY 11794 USA. [Dewi, Ruby; Bhalla, Kavita; Ou, Lihui; Hwang, Bor Jang; Liu, Wan-Ju] Univ Maryland, Sch Med, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Twaddel, William; Powers, R. Scott] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. [Boros, Laszlo G.] Univ Calif Los Angeles, Los Angeles Sch Med, Los Angeles, CA 90095 USA. [Boros, Laszlo G.] Los Angeles Biomed Res Inst LA BioMed, Torrance, CA 90502 USA. [Boros, Laszlo G.] SIDMAP, Torrance, CA 90502 USA. [Duraisamy, Sekhar; Drapkin, Ronny] Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. [Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Wong, Kwok-Kin] Harvard Univ, Sch Med, Boston, MA 02115 USA. [DeBerardinis, Ralph J.; Sudderth, Jessica] Univ Texas SW Med Ctr Dallas, Childrens Med Ctr, Res Inst, Dallas, TX 75390 USA. [Bhalla, Kavita; Ropell, Ashley E.; Gordon, Chris; Liu, Wan-Ju; Shroyer, Kenneth R.; Girnun, Geoffrey D.] SUNY Stony Brook, Sch Med, Dept Pathol, Stony Brook, NY 11794 USA. [Rohde, Jason M.; Boxer, Matthew B.] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA. RP Girnun, GD (reprint author), SUNY Stony Brook, Dept Pharmacol Sci, Stony Brook, NY 11794 USA. EM geoffrey.girnun@stonybrookmedicine.edu RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 FU NIH [CA169919, DK064685]; Maryland CRF; Stony Brook Research Foundation FX We thank Ms. Mallory for IHC work and Stony Brook Biorepository Core. Richard Hanson (OBM) for the PEPCK construct. This work was supported by NIH Grants CA169919 and DK064685, Maryland CRF and Stony Brook Research Foundation to G.D.G. The authors declare they have no conflict of interest related to the work presented. NR 36 TC 12 Z9 13 U1 3 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 EI 1097-4164 J9 MOL CELL JI Mol. Cell PD NOV 19 PY 2015 VL 60 IS 4 BP 571 EP 583 DI 10.1016/j.molcel.2015.09.025 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DB1SH UT WOS:000368288700008 PM 26481663 ER PT J AU Matthews, GM Mehdipour, P Cluse, LA Falkenberg, KJ Wang, E Roth, M Santoro, F Videos, E Stanley, K House, CM Rusche, JR Vakoc, CR Zuber, J Minucci, S Johnstone, RW AF Matthews, Geoffrey M. Mehdipour, Parinaz Cluse, Leonie A. Falkenberg, Katrina J. Wang, Eric Roth, Mareike Santoro, Fabio Videos, Eva Stanley, Kym House, Colin M. Rusche, James R. Vakoc, Christopher R. Zuber, Johannes Minucci, Saverio Johnstone, Ricky W. TI Functional-genetic dissection of HDAC dependencies in mouse lymphoid and myeloid malignancies SO BLOOD LA English DT Article ID HISTONE DEACETYLASE INHIBITORS; CANCER CELL-PROLIFERATION; MULTIPLE-MYELOMA; DNA-REPLICATION; CYCLE ARREST; COLON-CANCER; PPAR-GAMMA; THERAPY; DIFFERENTIATION; TRANSCRIPTION AB Histone deacetylase (HDAC) inhibitors (HDACis) have demonstrated activity in hematological and solid malignancies. Vorinostat, romidepsin, belinostat, and panobinostat are Food and Drug Administration approved for hematological malignancies and inhibit class II and/or class I HDACs, including HDAC1, 2, 3, and 6. We combined genetic and pharmacological approaches to investigate whether suppression of individual or multiple Hdacs phenocopied broad-acting H DACis in 3 genetically distinct leukemias and lymphomas. Individual Hdacs were depleted in murine acute myeloid leukemias (MLL-AF9;Nras(G12D); PML-RARet acute promyelocytic leukemia [APL] cells) and E mu-Myc lymphoma in vitro and in vivo. Strikingly, Hdac3-depleted cells were selected against in competitive assays for all 3 tumor types. Decreased proliferation following Hdac3 knockdown was not prevented by BCL-2 overexpression, caspase inhibition, or knockout of Cdknl a in ER-Myc lymphoma, and depletion of Hdac3 in vivo significantly reduced tumor burden. Interestingly, APL cells depleted of Hdac3 demonstrated a more differentiated phenotype. Consistent with these genetic studies, the HDAC3 inhibitor RGFP966 reduced proliferation of ER-Myc lymphoma and induced differentiation in APL. Genetic codepletion of Hdac1 with Hdac2 was pro-apoptotic in ER-Myc lymphoma in vitro and in vivo and was phenocopied by the HDAC1/2specific agent RGFP233. This study demonstrates the importance of HDAC3 for the proliferation of leukemia and lymphoma cells, suggesting that HDAC3-selective inhibitors could prove useful for thetreatment of hematological malignancies. Moreover, our results demonstrate that codepletion of Hdacl with Hdac2 mediates a robust pro-apoptotic response. Our integrated genetic and pharmacological approach provides important insights into the individual or combinations of HDACs that could be prioritized for targeting in a range of hematological malignancies. C1 [Matthews, Geoffrey M.; Cluse, Leonie A.; Falkenberg, Katrina J.; Videos, Eva; Stanley, Kym; Johnstone, Ricky W.] Peter Mac Callum Canc Ctr, Canc Therapeut Program, East Melbourne, Vic, Australia. [Matthews, Geoffrey M.; Cluse, Leonie A.; Videos, Eva; Stanley, Kym; House, Colin M.; Johnstone, Ricky W.] Univ Melbourne, Dept Oncol, Sir Peter Mac Callum, Parkville, Vic 3052, Australia. [Mehdipour, Parinaz; Santoro, Fabio; Minucci, Saverio] European Inst Oncol, Dept Expt Oncol, Milan, Italy. [Falkenberg, Katrina J.; Roth, Mareike; Zuber, Johannes] Vienna Bioctr, Res Inst Mol Pathol, Vienna, Austria. [Falkenberg, Katrina J.] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. [Wang, Eric; Vakoc, Christopher R.] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Rusche, James R.] Repligen Corp, Waltham, MA USA. [Minucci, Saverio] European Inst Oncol, Trug Dev Program, Milan, Italy. [Minucci, Saverio] Univ Milan, Dept Biosci, Milan, Italy. RP Matthews, GM (reprint author), Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Dept Med,Med Sch, 450 Brookline Ave,Harvard Inst Med Bldg, Boston, MA 02215 USA. EM geoffreym_matthews@dfci.harvard.edu; saverio.minucci@ieo.eu; rickyjohnstone@petermac.org FU National Health and Medical Research Council (NHMRC) Biomedical Fellowship; Peter MacCallum Cancer Foundation; Fondazione Italiana per la ricerca sul cancro (FIRC); National Institutes of Health [CA 174793]; Burroughs-Wellcome Fund; Alex's Lemonade Stand Foundation "A" Award; NHMRC; Cancer Council Victoria; Leukemia Foundation of Australia; Victorian Cancer Agency; Australian Rotary Health Foundation; ERC [36860]; Special Research Program of the Austrian Science Fund [F4710]; Boehringer Ingelheim; Italian Association for Cancer Research; FIRC; National Research Council; European Community [277899] FX This work was supported by a National Health and Medical Research Council (NHMRC) Biomedical Fellowship and a Peter MacCallum Cancer Foundation Grant (G.M.M.); a Fondazione Italiana per la ricerca sul cancro (FIRC) fellowship (P.M.); National Institutes of Health (grant CA 174793), Burroughs-Wellcome Fund Career Award for Medical Scientists, and Alex's Lemonade Stand Foundation "A" Award (C.R.V.); and NHMRC Program and Project Grants (Senior Principal Research Fellow), Cancer Council Victoria, Leukemia Foundation of Australia, Victorian Cancer Agency, and Australian Rotary Health Foundation (R.W.J.). Laboratory research is funded by an ERC Starting Grant (36860), Special Research Program of the Austrian Science Fund (grant F4710), and Boehringer Ingelheim (J.Z.); the Italian Association for Cancer Research, FIRC, National Research Council Flagship Project Epigen, and European Community (4D Cell Fate Project 277899) (S.M.). NR 64 TC 13 Z9 13 U1 1 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD NOV 19 PY 2015 VL 126 IS 21 BP 2392 EP 2403 DI 10.1182/blood-2015-03-632984 PG 12 WC Hematology SC Hematology GA CY4QY UT WOS:000366394500010 PM 26447190 ER PT J AU Michor, F Beal, K AF Michor, Franziska Beal, Kathryn TI Improving Cancer Treatment via Mathematical Modeling: Surmounting the Challenges Is Worth the Effort SO CELL LA English DT Review ID STAGE BREAST-CANCER; DRUG-RESISTANCE; INTRATUMOR HETEROGENEITY; RADIATION-THERAPY; RANDOMIZED-TRIAL; TUMOR SIZE; CHEMOTHERAPY; EVOLUTION; LEUKEMIA; SURVIVAL AB Drug delivery schedules are key factors in the efficacy of cancer therapies, and mathematical modeling of population dynamics and treatment responses can be applied to identify better drug administration regimes as well as provide mechanistic insights. To capitalize on the promise of this approach, the cancer field must meet the challenges of moving this type of work into clinics. C1 [Michor, Franziska] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Michor, Franziska] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Beal, Kathryn] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10065 USA. RP Michor, F (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. EM michor@jimmy.harvard.edu; bealk@mskcc.org FU NCI NIH HHS [P30 CA008748, U54 CA143798, U54 CA193461] NR 41 TC 7 Z9 7 U1 3 U2 13 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD NOV 19 PY 2015 VL 163 IS 5 BP 1059 EP 1063 DI 10.1016/j.cell.2015.11.002 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CX9SD UT WOS:000366044700007 PM 26590416 ER PT J AU Yeap, LS Hwang, JK Du, Z Meyers, RM Meng, FL Jakubauskaite, A Liu, MY Mani, V Neuberg, D Kepler, TB Wang, JH Alt, FW AF Yeap, Leng-Siew Hwang, Joyce K. Du, Zhou Meyers, Robin M. Meng, Fei-Long Jakubauskaite, Agne Liu, Mengyuan Mani, Vinidhra Neuberg, Donna Kepler, Thomas B. Wang, Jing H. Alt, Frederick W. TI Sequence-Intrinsic Mechanisms that Target AID Mutational Outcomes on Antibody Genes SO CELL LA English DT Article ID CLASS-SWITCH RECOMBINATION; CENTER B-CELLS; SOMATIC HYPERMUTATION; NEUTRALIZING ANTIBODIES; GENOMIC INSTABILITY; DNA; REGION; DELETIONS; TRANSCRIPTION; ACCUMULATION AB In activated B lymphocytes, AID initiates antibody variable (V) exon somatic hypermutation (SHM) for affinity maturation in germinal centers (GCs) and IgH switch (S) region DNA breaks (DSBs) for class-switch recombination (CSR). To resolve long-standing questions, we have developed an in vivo assay to study AID targeting of passenger sequences replacing a V exon. First, we find AID targets SHM hot-spots within V exon and S region passengers at similar frequencies and that the normal SHM process frequently generates deletions, indicating that SHM and CSR employ the same mechanism. Second, AID mutates targets in diverse non-Ig passengers in GC B cells at levels similar to those of V exons, definitively establishing the V exon location as "privileged" for SHM. Finally, Peyer's patch GC B cells generate a reservoir of V exons that are highly mutated before selection for affinity maturation. We discuss the implications of these findings for harnessing antibody diversification mechanisms. C1 [Yeap, Leng-Siew; Hwang, Joyce K.; Du, Zhou; Meyers, Robin M.; Meng, Fei-Long; Jakubauskaite, Agne; Liu, Mengyuan; Mani, Vinidhra; Wang, Jing H.; Alt, Frederick W.] Harvard Univ, Sch Med, Boston Childrens Hosp, Howard Hughes Med Inst,Program Cellular & Mol Med, Boston, MA 02115 USA. [Yeap, Leng-Siew; Hwang, Joyce K.; Du, Zhou; Meyers, Robin M.; Meng, Fei-Long; Jakubauskaite, Agne; Liu, Mengyuan; Mani, Vinidhra; Wang, Jing H.; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Kepler, Thomas B.] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02215 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Boston Childrens Hosp, Howard Hughes Med Inst,Program Cellular & Mol Med, 300 Longwood Ave, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu RI Wang, Jing/M-7813-2015 OI Wang, Jing/0000-0003-4343-2527 FU NIH [R01AI077595, 5UM1AI100645, R21AI110777-01A1, R21CA184707-01A1, R01CA166325-01A1, F30AI114179-01A1]; Dana Farber/Harvard Cancer Center Core Grant [5P30 CA006516]; Boettcher Foundation Webb-Waring Biomedical Research Award; Cancer League of Colorado; American Society of Hematology Scholar Award FX The authors thank Dr. Kefei Yu for the RMCE exchange plasmid, Klaus Rajewsky for the JH targeting construct, Pei-Yi Huang and Yuko Fujiwara for generating the chimeras, Kenneth Ketman and Natasha Barteneva for help with FACS sorting, and Garnett Kelsoe for helpful discussions. This work was supported by NIH grants (R01AI077595 and CHAVI-ID 5UM1AI100645 to F.W.A.; R21AI110777-01A1, R21CA184707-01A1, and R01CA166325-01A1 to J.H.W.). J.K.H. was supported by an NIH grant (F30AI114179-01A1). D.N. is supported by a Dana Farber/Harvard Cancer Center Core Grant (5P30 CA006516). J.H.W. is also supported by a Boettcher Foundation Webb-Waring Biomedical Research Award, an American Society of Hematology Scholar Award, and the Cancer League of Colorado. F.W.A. is an investigator and Z.D. is a postdoctoral fellow of the Howard Hughes Medical Institute. L.S.Y. was a Cancer Research Institute postdoctoral fellow, and F.-L.M. is a Lymphoma Research Foundation postdoctoral fellow. NR 45 TC 21 Z9 21 U1 3 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD NOV 19 PY 2015 VL 163 IS 5 BP 1124 EP 1137 DI 10.1016/j.cell.2015.10.042 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CX9SD UT WOS:000366044700012 PM 26582132 ER PT J AU Ru, H Chambers, MG Fu, TM Tong, AB Liao, MF Wu, H AF Ru, Heng Chambers, Melissa G. Fu, Tian-Min Tong, Alexander B. Liao, Maofu Wu, Hao TI Molecular Mechanism of V(D)J Recombination from Synaptic RAG1-RAG2 Complex Structures SO CELL LA English DT Article ID CHROMOSOMAL TRANSLOCATIONS; CRYSTAL-STRUCTURE; DNA; ORGANIZATION; RAG-1 AB Diverse repertoires of antigen-receptor genes that result from combinatorial splicing of coding segments by V(D)J recombination are hallmarks of vertebrate immunity. The (RAG1-RAG2)(2) recombinase (RAG) recognizes recombination signal sequences (RSSs) containing a heptamer, a spacer of 12 or 23 base pairs, and a nonamer (12-RSS or 23-RSS) and introduces precise breaks at RSS-coding segment junctions. RAG forms synaptic complexes only with one 12-RSS and one 23-RSS, a dogma known as the 12/23 rule that governs the recombination fidelity. We report cryo-electron microscopy structures of synaptic RAG complexes at up to 3.4 angstrom resolution, which reveal a closed conformation with base flipping and base-specific recognition of RSSs. Distortion at RSS-coding segment junctions and base flipping in coding segments uncover the two-metal-ion catalytic mechanism. Induced asymmetry involving tilting of the nonamer-binding domain dimer of RAG1 upon binding of HMGB1-bent 12-RSS or 23-RSS underlies the molecular mechanism for the 12/23 rule. C1 [Ru, Heng; Fu, Tian-Min; Tong, Alexander B.; Wu, Hao] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Ru, Heng; Fu, Tian-Min; Tong, Alexander B.; Wu, Hao] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Chambers, Melissa G.; Liao, Maofu] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Liao, MF (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM maofu_liao@hms.harvard.edu; wu@crystal.harvard.edu FU Cancer Research Institute Irvington Postdoctoral Fellowship FX We thank Dr. Wei Mi for help with sample freezing for cryo-EM studies, Drs. Liron David and Maria Ericsson for help with negative-stain EM experiments, Drs. Yang Li and Wei Ding for suggestions on model building and refinement, and the support of the Cancer Research Institute Irvington Postdoctoral Fellowship (to H.R.). NR 20 TC 14 Z9 14 U1 1 U2 15 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD NOV 19 PY 2015 VL 163 IS 5 BP 1138 EP 1152 DI 10.1016/j.cell.2015.10.055 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CX9SD UT WOS:000366044700013 PM 26548953 ER PT J AU Sparano, JA Gray, RJ Makower, DF Pritchard, KI Albain, KS Hayes, DF Geyer, CE Dees, EC Perez, EA Olson, JA Zujewski, JA Lively, T Badve, SS Saphner, TJ Wagner, LI Whelan, TJ Ellis, MJ Paik, S Wood, WC Ravdin, P Keane, MM Moreno, HLG Reddy, PS Goggins, TF Mayer, IA Brufsky, AM Toppmeyer, DL Kaklamani, VG Atkins, JN Berenberg, JL Sledge, GW AF Sparano, J. A. Gray, R. J. Makower, D. F. Pritchard, K. I. Albain, K. S. Hayes, D. F. Geyer, C. E., Jr. Dees, E. C. Perez, E. A. Olson, J. A., Jr. Zujewski, J. A. Lively, T. Badve, S. S. Saphner, T. J. Wagner, L. I. Whelan, T. J. Ellis, M. J. Paik, S. Wood, W. C. Ravdin, P. Keane, M. M. Gomez Moreno, H. L. Reddy, P. S. Goggins, T. F. Mayer, I. A. Brufsky, A. M. Toppmeyer, D. L. Kaklamani, V. G. Atkins, J. N. Berenberg, J. L. Sledge, G. W. TI Prospective Validation of a 21-Gene Expression Assay in Breast Cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIALS; CLINICAL-PRACTICE; AMERICAN SOCIETY; GENE-EXPRESSION; TUMOR-MARKERS; TAMOXIFEN; RECURRENCE; EFFICACY; WOMEN AB BACKGROUND Prior studies with the use of a prospective-retrospective design including archival tumor samples have shown that gene-expression assays provide clinically useful prognostic information. However, a prospectively conducted study in a uniformly treated population provides the highest level of evidence supporting the clinical validity and usefulness of a biomarker. METHODS We performed a prospective trial involving women with hormone-receptor-positive, human epidermal growth factor receptor type 2 (HER2)-negative, axillary node-negative breast cancer with tumors of 1.1 to 5.0 cm in the greatest dimension (or 0.6 to 1.0 cm in the greatest dimension and intermediate or high tumor grade) who met established guidelines for the consideration of adjuvant chemotherapy on the basis of clinicopathologic features. A reverse-transcriptase-polymerase-chain-reaction assay of 21 genes was performed on the paraffin-embedded tumor tissue, and the results were used to calculate a score indicating the risk of breast-cancer recurrence; patients were assigned to receive endocrine therapy without chemotherapy if they had a recurrence score of 0 to 10, indicating a very low risk of recurrence (on a scale of 0 to 100, with higher scores indicating a greater risk of recurrence). RESULTS Of the 10,253 eligible women enrolled, 1626 women (15.9%) who had a recurrence score of 0 to 10 were assigned to receive endocrine therapy alone without chemotherapy. At 5 years, in this patient population, the rate of invasive disease-free survival was 93.8% (95% confidence interval [CI], 92.4 to 94.9), the rate of freedom from recurrence of breast cancer at a distant site was 99.3% (95% CI, 98.7 to 99.6), the rate of freedom from recurrence of breast cancer at a distant or local-regional site was 98.7% (95% CI, 97.9 to 99.2), and the rate of overall survival was 98.0% (95% CI, 97.1 to 98.6). CONCLUSIONS Among patients with hormone-receptor-positive, HER2-negative, axillary node-negative breast cancer who met established guidelines for the recommendation of adjuvant chemotherapy on the basis of clinicopathologic features, those with tumors that had a favorable gene-expression profile had very low rates of recurrence at 5 years with endocrine therapy alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00310180.) C1 [Sparano, J. A.; Makower, D. F.] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. [Gray, R. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pritchard, K. I.] Sunnybrook Res Inst, Toronto, ON, Canada. [Whelan, T. J.] Juravinski Canc Ctr, Hamilton, ON, Canada. [Albain, K. S.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Wagner, L. I.; Kaklamani, V. G.] Northwestern Univ, Chicago, IL 60611 USA. [Hayes, D. F.] Univ Michigan, Ann Arbor, MI 48109 USA. [Geyer, C. E., Jr.] Virginia Commonwealth Univ, Sch Med, Richmond, NC USA. [Geyer, C. E., Jr.] Massey Canc Ctr, Richmond, NC USA. [Dees, E. C.] Univ N Carolina, Chapel Hill, NC USA. [Olson, J. A., Jr.] Duke Univ, Med Ctr, Durham, NC USA. [Wagner, L. I.] Wake Forest Univ Hlth Serv, Winston Salem, NC USA. [Atkins, J. N.] Southeast Clin Oncol Res Consortium, Goldsboro, NC USA. [Perez, E. A.] Mayo Clin, Jacksonville, FL 32224 USA. [Olson, J. A., Jr.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Zujewski, J. A.; Lively, T.] NIH, Bethesda, MD 20892 USA. [Badve, S. S.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Sledge, G. W.] Indiana Univ Hosp, Indianapolis, IN 46202 USA. [Saphner, T. J.] Vince Lombardi Canc Clin, Two Rivers, WI USA. [Goggins, T. F.] Fox Valley Hematol & Oncol, Appleton, WI USA. [Ellis, M. J.] Baylor Coll Med, Houston, TX 77030 USA. [Ravdin, P.] Univ Texas San Antonio, San Antonio, TX USA. [Ellis, M. J.] Washington Univ, St Louis, MO USA. [Paik, S.] Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. [Brufsky, A. M.] Univ Pittsburgh, Pittsburgh, PA USA. [Paik, S.] Yonsei Univ, Dept Med Oncol, Coll Med, Seoul, South Korea. [Paik, S.] Yonsei Univ, Breast Ctr, Coll Med, Seoul, South Korea. [Wood, W. C.] Emory Univ, Atlanta, GA 30322 USA. [Keane, M. M.] Irish Clin Oncol Res Grp, Dublin, Ireland. [Gomez Moreno, H. L.] Inst Nacl Enfermedades Neoplas, Lima, Peru. [Reddy, P. S.] Canc Ctr Kansas, Wichita, KS USA. [Mayer, I. A.] Vanderbilt Univ, Nashville, TN 37235 USA. [Toppmeyer, D. L.] Rutgers Canc Inst New Jersey, New Brunswick, NJ 08903 USA. [Berenberg, J. L.] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA. [Sledge, G. W.] Stanford Univ, Stanford, CA 94305 USA. RP Sparano, JA (reprint author), Montefiore Med Ctr, Dept Oncol, 1695 Eastchester Rd, Bronx, NY 10461 USA. EM jsparano@montefiore.org RI Whelan, Timothy/D-3185-2017 FU National Cancer Institute FX Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00310180. NR 37 TC 112 Z9 115 U1 8 U2 23 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 19 PY 2015 VL 373 IS 21 BP 2005 EP 2014 DI 10.1056/NEJMoa1510764 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CW4JN UT WOS:000364957700006 PM 26412349 ER PT J AU Stankovic, KM Tan, OT Sadow, PM AF Stankovic, Konstantina M. Tan, Oon T. Sadow, Peter M. TI Case 36-2015: A 27-Year-Old Woman with a Lesion of the Ear Canal SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID T-CELL LYMPHOMA; ANGIOLYMPHOID HYPERPLASIA; EOSINOPHILIA; LASER C1 [Stankovic, Konstantina M.] Massachusetts Gen Hosp, Dept Otolaryngol, Boston, MA 02114 USA. [Sadow, Peter M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Stankovic, Konstantina M.; Sadow, Peter M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Tan, Oon T.] Massachusetts Eye & Ear Infirm, Dept Laser & Reconstruct Surg, Boston, MA 02114 USA. [Stankovic, Konstantina M.; Tan, Oon T.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Sadow, Peter M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Stankovic, KM (reprint author), Massachusetts Gen Hosp, Dept Otolaryngol, Boston, MA 02114 USA. NR 14 TC 0 Z9 0 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 19 PY 2015 VL 373 IS 21 BP 2070 EP 2077 DI 10.1056/NEJMcpc1410941 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA CW4JN UT WOS:000364957700013 PM 26581000 ER PT J AU Kaafarani, HMA AF Kaafarani, Haytham M. A. TI Tension Pneumoperitoneum SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Kaafarani, Haytham M. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kaafarani, HMA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM hkaafarani@mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 19 PY 2015 VL 373 IS 21 BP E24 EP E24 DI 10.1056/NEJMicm1500045 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CW4JN UT WOS:000364957700001 PM 26581011 ER PT J AU Mufson, EJ Mahady, L Waters, D Counts, SE Perez, SE Dekosky, ST Ginsberg, SD Ikonomovic, MD Scheff, SW Binder, LI AF Mufson, E. J. Mahady, L. Waters, D. Counts, S. E. Perez, S. E. Dekosky, S. T. Ginsberg, S. D. Ikonomovic, M. D. Scheff, S. W. Binder, L. I. TI HIPPOCAMPAL PLASTICITY DURING THE PROGRESSION OF ALZHEIMER'S DISEASE SO NEUROSCIENCE LA English DT Article DE hippocampus; Alzheimer's disease; neurotrophins; mild cognitive impairment; plasticity degeneration ID MILD COGNITIVE IMPAIRMENT; NERVE GROWTH-FACTOR; CHOLINERGIC BASAL FOREBRAIN; ENDOSOMAL-LYSOSOMAL SYSTEM; AMYLOID PRECURSOR PROTEIN; POSTSYNAPTIC GLUTAMATERGIC FUNCTION; VITRO AUTORADIOGRAPHIC ANALYSIS; LESION-INDUCED SYNAPTOGENESIS; PERFORANT-PATH TRANSECTION; ENTORHINAL CORTEX NEURONS AB Neuroplasticity involves molecular and structural changes in central nervous system (CNS) throughout life. The concept of neural organization allows for remodeling as a compensatory mechanism to the early pathobiology of Alzheimer's disease (AD) in an attempt to maintain brain function and cognition during the onset of dementia. The hippocampus, a crucial component of the medial temporal lobe memory circuit, is affected early in AD and displays synaptic and intraneuronal molecular remodeling against a pathological background of extracellular amyloid-beta (A beta) deposition and intracellular neurofibrillary tangle (NFT) formation in the early stages of AD. Here we discuss human clinical pathological findings supporting the concept that the hippocampus is capable of neural plasticity during mild cognitive impairment (MCI), a prodromal stage of AD and early stage AD. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Mufson, E. J.; Mahady, L.; Waters, D.] St Josephs Med Ctr, Barrow Neurol Inst, Dept Neurobiol, Phoenix, AZ 85013 USA. [Counts, S. E.; Binder, L. I.] Michigan State Univ, Coll Human Med, Dept Translat Sci & Mol Med, Grand Rapids, MI USA. [Perez, S. E.] Rush Univ, Med Ctr, Div Neurol Sci, Chicago, IL 60612 USA. [Dekosky, S. T.] Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA USA. [Ginsberg, S. D.] NYU, Langone Med Ctr, Ctr Dementia Res, Nathan Kline Inst,Dept Psychiat, Orangeburg, NY USA. [Ginsberg, S. D.] NYU, Langone Med Ctr, Dept Physiol & Neurosci, Orangeburg, NY USA. [Ikonomovic, M. D.] Univ Pittsburgh, Geriatr Res Educ & Clin Ctr, VA Pittsburgh Healthcare Syst, Dept Neurol, Pittsburgh, PA USA. [Ikonomovic, M. D.] Univ Pittsburgh, Geriatr Res Educ & Clin Ctr, VA Pittsburgh Healthcare Syst, Dept Psychiat, Pittsburgh, PA USA. [Scheff, S. W.] Univ Kentucky, Sanders Brown Ctr Aging, Lexington, KY 40536 USA. RP Mufson, EJ (reprint author), Barrow Neurol Inst, Alzheimers Dis Res Lab, 350 W Thomas St, Phoenix, AZ 85013 USA. EM elliott.mufson@dignityhealth.org OI Ginsberg, Stephen/0000-0002-1797-4288 FU National Institute on Aging, National Institutes of Health [PO1AG014449, RO1AG043375, RO1AG042475, PO1AG025204, PO1AG107617, P30AG019610, P30AG10161]; Alzheimer's Association FX This study was supported by grants PO1AG014449, RO1AG043375, RO1AG042475, PO1AG025204, PO1AG107617, P30AG019610 and P30AG10161 from the National Institute on Aging, National Institutes of Health and the Alzheimer's Association. We are indebted to the Catholic nuns, priests, and lay brothers who participated in the Rush Religious Orders Study, the University of Kentucky RADC clinical cohort and to all ADC center participants that provided clinical and pathological data to the various studies discussed in this review. NR 232 TC 16 Z9 16 U1 6 U2 21 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD NOV 19 PY 2015 VL 309 BP 51 EP 67 DI 10.1016/j.neuroscience.2015.03.006 PG 17 WC Neurosciences SC Neurosciences & Neurology GA CV3EV UT WOS:000364142300004 PM 25772787 ER PT J AU Dietrich, J Prust, M Kaiser, J AF Dietrich, J. Prust, M. Kaiser, J. TI CHEMOTHERAPY, COGNITIVE IMPAIRMENT AND HIPPOCAMPAL TOXICITY SO NEUROSCIENCE LA English DT Review DE chemotherapy; neurotoxicity; hippocampus; neural progenitor cells; cognitive dysfunction ID BREAST-CANCER SURVIVORS; ACUTE LYMPHOBLASTIC-LEUKEMIA; CELL-PROLIFERATION; MEMORY DEFICITS; ADJUVANT CHEMOTHERAPY; 5-FLUOROURACIL CHEMOTHERAPY; ADULT NEUROGENESIS; FUNCTIONAL-ROLE; SPATIAL MEMORY; DRUG THIOTEPA AB Cancer therapies can be associated with significant central nervous system (CNS) toxicity. While radiation-induced brain damage has been long recognized both in pediatric and adult cancer patients, CNS toxicity from chemotherapy has only recently been acknowledged. Clinical studies suggest that the most frequent neurotoxic adverse effects associated with chemotherapy include memory and learning deficits, alterations of attention, concentration, processing speed and executive function. Preclinical studies have started to shed light on how chemotherapy targets the CNS both on cellular and molecular levels to disrupt neural function and brain plasticity. Potential mechanisms include direct cellular toxicity, alterations in cellular metabolism, oxidative stress, and induction of pro-inflammatory processes with subsequent disruption of normal cellular and neurological function. Damage to neural progenitor cell populations within germinal zones of the adult CNS has been identified as one of the key mechanisms by which chemotherapy might exert long-lasting and progressive neurotoxic effects. Based on the important role of the hippocampus for maintenance of brain plasticity throughout life, several experimental studies have focused on the study of chemotherapy effects on hippocampal neurogenesis and associated learning and memory. An increasing body of literature from both animal studies and neuroimaging studies in cancer patients suggests a possible relationship between chemotherapy induced hippocampal damage and the spectrum of neurocognitive deficits and mood alterations observed in cancer patients. This review aims to briefly summarize current preclinical and neuroimaging studies that are providing a potential link between the neurotoxic effects of chemotherapy and hippocampal dysfunction, highlighting challenges and future directions in this field of investigation. This article is part of a Special Issue entitled: Hippocampus. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Dietrich, J.] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Sch Med, Boston, MA 02114 USA. [Prust, M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Athinoula A Martinos Ctr Biomed Imaging,Dept Radi, Boston, MA 02114 USA. [Kaiser, J.] Goethe Univ Frankfurt, Fac Med, Inst Med Psychol, D-60528 Frankfurt, Germany. RP Dietrich, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, MGH Canc Ctr, Dept Neurol,Sch Med, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM Dietrich.Jorg@mgh.harvard.edu FU Institutional Research Grant from the American Cancer Society; American Academy of Neurology (AAN) Clinical Research Training Fellowship (CRTF) FX The authors gratefully acknowledge support from an Institutional Research Grant from the American Cancer Society (to JD). JD is a recipient of an American Academy of Neurology (AAN) Clinical Research Training Fellowship (CRTF). This work also has been made possible through philanthropic support and generous donations from R. Tawil and the S. McPhee family foundations. NR 101 TC 11 Z9 11 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD NOV 19 PY 2015 VL 309 BP 224 EP 232 DI 10.1016/j.neuroscience.2015.06.016 PG 9 WC Neurosciences SC Neurosciences & Neurology GA CV3EV UT WOS:000364142300017 PM 26086545 ER PT J AU Lee, Y Xu, CJ Sebastin, M Lee, A Holwell, N Xu, CV Nieves, DM Mu, LY Langer, RS Lin, CP Karp, JM AF Lee, Yuhan Xu, Chenjie Sebastin, Monisha Lee, Albert Holwell, Nathan Xu, Calvin Nieves, David Miranda Mu, Luye Langer, Robert S. Lin, Charles P. Karp, Jeffrey M. TI Bioinspired Nanoparticulate Medical Glues for Minimally Invasive Tissue Repair SO ADVANCED HEALTHCARE MATERIALS LA English DT Article ID PHRAGMATOPOMA-CALIFORNICA FEWKES; HAGEN-POISEUILLE FLOW; MUSSEL ADHESION; SURFACE RECONSTRUCTION; 2-OCTYL CYANOACRYLATE; SANDCASTLE WORM; FIBRIN GLUE; BARNACLE; SURGERY; NEEDLE AB Delivery of tissue glues through small-bore needles or trocars is critical for sealing holes, affixing medical devices, or attaching tissues together during minimally invasive surgeries. Inspired by the granule-packaged glue delivery system of sandcastle worms, a nanoparticulate formulation of a viscous hydrophobic light-activated adhesive based on poly(glycerol sebacate)-acrylate is developed. Negatively charged alginate is used to stabilize the nanoparticulate surface to significantly reduce its viscosity and to maximize injectability through small-bore needles. The nanoparticulate glues can be concentrated to approximate to 30 w/v% dispersions in water that remain localized following injection. With the trigger of a positively charged polymer (e.g., protamine), the nanoparticulate glues can quickly assemble into a viscous glue that exhibits rheological, mechanical, and adhesive properties resembling the native poly(glycerol sebacate)-acrylate based glues. This platform should be useful to enable the delivery of viscous glues to augment or replace sutures and staples during minimally invasive procedures. C1 [Lee, Yuhan; Xu, Chenjie; Sebastin, Monisha; Lee, Albert; Holwell, Nathan; Xu, Calvin; Nieves, David Miranda; Mu, Luye; Karp, Jeffrey M.] Harvard Univ, Sch Med, Harvard MIT Div Hlth Sci & Technol,Harvard Stem C, Dept Med,Ctr Regenerat Therapeut,Brigham & Womens, Cambridge, MA 02139 USA. [Langer, Robert S.] MIT, Harvard Massachusetts Inst Technol, Div HealthSci & Technol,Dept Chem Engn, Inst Med Engn & Sci,David H Koch Inst Integrat Ca, Cambridge, MA 02139 USA. [Lin, Charles P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02140 USA. RP Karp, JM (reprint author), Harvard Univ, Sch Med, Harvard MIT Div Hlth Sci & Technol,Harvard Stem C, Dept Med,Ctr Regenerat Therapeut,Brigham & Womens, 65 Landsdowne St, Cambridge, MA 02139 USA. EM jmkarp@partners.org RI xu, chenjie/E-4075-2012; OI Xu, Chenjie/0000-0002-8278-3912; Holwell, Nathan/0000-0002-6268-2057 FU National Institutes of Health (NIH) [GM086433, DE013023]; Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education of Korea [2012R1A6A3A03041166] FX Y.L. and C.X. contributed equally to this work. Authors thank Maria J.N. Pereira and Sai Chavala for thoughtful discussions. This work was supported by National Institutes of Health (NIH) grant GM086433 to J.M.K., NIH grant DE013023 to R.S.L., and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education of Korea (2012R1A6A3A03041166) to Y.L. J.M.K. and R.S.L. hold equity in Gecko Biomedical, a company that has an option to license IP generated by J.M.K. and R.S.L. and that may benefit financially if the IP is licensed and further validated. The interests of J.M.K and R.S.L. were reviewed and are subject to a management plan overseen by their institutions in accordance with their conflict of interest policies. NR 45 TC 3 Z9 3 U1 13 U2 29 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2192-2640 EI 2192-2659 J9 ADV HEALTHC MATER JI Adv. Healthc. Mater. PD NOV 18 PY 2015 VL 4 IS 16 BP 2587 EP 2596 DI 10.1002/adhm.201500419 PG 10 WC Engineering, Biomedical; Nanoscience & Nanotechnology; Materials Science, Biomaterials SC Engineering; Science & Technology - Other Topics; Materials Science GA DA9PP UT WOS:000368142100016 PM 26227833 ER PT J AU Chrastil, ER Sherrill, KR Hasselmo, ME Stern, CE AF Chrastil, Elizabeth R. Sherrill, Katherine R. Hasselmo, Michael E. Stern, Chantal E. TI There and Back Again: Hippocampus and Retrosplenial Cortex Track Homing Distance during Human Path Integration SO JOURNAL OF NEUROSCIENCE LA English DT Article DE angular gyrus; fMRI; medial prefrontal cortex; navigation; parahippocampal cortex; precuneus ID DIRECTED SPATIAL NAVIGATION; ENTORHINAL CORTEX; PARIETAL CORTEX; HEAD-DIRECTION; NONVISUAL NAVIGATION; TEMPORAL LOBECTOMY; DECISION-MAKING; COGNITIVE MAP; NEURAL BASIS; REPRESENTATION AB Path integration, the updating of position and orientation during movement, often involves tracking a home location. Here, we examine processes that could contribute to successful location tracking in humans. In particular, we investigate a homing vector model of path integration, whereby a navigator continuously tracks a trajectory back to the home location. To examine this model, we developed a loop task for fMRI, in which participants viewed movement that circled back to a home location in a sparse virtual environment. In support of a homing vector system, hippocampus, retrosplenial cortex, and parahippocampal cortex were responsive to Euclidean distance from home. These results provide the first evidence of a constantly maintained homing signal in the human brain. In addition, hippocampus, retrosplenial cortex, and parahippocampal cortex, as well as medial prefrontal cortex, were recruited during successful path integration. These findings suggest that dynamic processes recruit hippocampus, retrosplenial cortex, and parahippocampal cortex in support of path integration, including a homing vector system that tracks movement relative to home. C1 [Chrastil, Elizabeth R.; Sherrill, Katherine R.; Hasselmo, Michael E.; Stern, Chantal E.] Boston Univ, Dept Psychol & Brain Sci, Boston, MA 02215 USA. [Chrastil, Elizabeth R.; Sherrill, Katherine R.; Hasselmo, Michael E.; Stern, Chantal E.] Boston Univ, Ctr Memory & Brain, Boston, MA 02215 USA. [Chrastil, Elizabeth R.; Sherrill, Katherine R.; Stern, Chantal E.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Chrastil, ER (reprint author), Boston Univ, Ctr Memory & Brain, 2 Cummington Mall, Boston, MA 02215 USA. EM chrastil@bu.edu OI Hasselmo, Michael/0000-0002-9925-6377; Chrastil, Elizabeth/0000-0003-2544-0152 FU Office of Naval Research MURI [N000 14-10-1-0936]; NCRR [P41RR14075] FX This work was supported by Office of Naval Research MURI N000 14-10-1-0936. fMRI scanning was completed at the Athinoula A. Martinos Center for Biomedical Imaging (Charlestown, MA), which receives support from NCRR P41RR14075. We thank Andrew Whiteman, Rachel Nauer, and Allen Chang for their assistance; and Sam Ling and Marc Howard for helpful comments. NR 72 TC 7 Z9 7 U1 1 U2 12 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 18 PY 2015 VL 35 IS 46 BP 15442 EP 15452 DI 10.1523/JNEUROSCI.1209-15.2015 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CX9VT UT WOS:000366054500020 PM 26586830 ER PT J AU Hwang, MJ Zsido, RG Song, HJ Pace-Schott, EF Miller, KK Lebron-Milad, K Marin, MF Milad, MR AF Hwang, Moon Jung Zsido, Rachel G. Song, Huijin Pace-Schott, Edward F. Miller, Karen Klahr Lebron-Milad, Kelimer Marin, Marie-France Milad, Mohammed R. TI Contribution of estradiol levels and hormonal contraceptives to sex differences within the fear network during fear conditioning and extinction SO BMC PSYCHIATRY LA English DT Article DE Gonadal hormones; Estrogens; Estradiol; Sex differences; Fear conditioning; Extinction memory; Men; Women; Conditioned response; Unconditioned response; fMRI ID POSTTRAUMATIC-STRESS-DISORDER; MENSTRUAL-CYCLE PHASE; BRAIN ACTIVATION; FEMALE RATS; PREFRONTAL CORTEX; AMYGDALA ACTIVITY; WOMEN; EXPRESSION; ESTROGEN; HUMANS AB Background: Findings about sex differences in the field of fear conditioning and fear extinction have been mixed. At the psychophysiological level, sex differences emerge only when taking estradiol levels of women into consideration. This suggests that this hormone may also influence sex differences with regards to activations of brain regions involved in fear conditioning and its extinction. Importantly, the neurobiological correlates associated with the use of hormonal oral contraceptives in women have not been fully contrasted against men and against naturally cycling women with different levels of estradiol. In this study, we begin to fill these scientific gaps. Methods: We recruited 37 healthy men and 48 healthy women. Of these women, 16 were using oral contraceptives (OC) and 32 were naturally cycling. For these naturally cycling women, a median split was performed on their serum estradiol levels to create a high estradiol (HE) group (n = 16) and a low estradiol (LE) group (n = 16). All participants underwent a 2-day fear conditioning and extinction paradigm in a 3 T MR scanner. Using the 4 groups (men, HE women, LE women, and OC users) and controlling for age and coil type, one-way ANCOVAs were performed to look at significant activations within the nodes of the fear circuit. Using post-hoc analyses, beta-weights were extracted in brain regions showing significant effects in order to unveil the differences based on hormonal status (men, HE, LE, OC). Results: Significant main effect of hormonal status group was found across the different phases of the experiment and in different sub-regions of the insular and cingulate cortices, amygdala, hippocampus, and hypothalamus. During conditioning, extinction and recall, most of the observed differences suggested higher activations among HE women relative to men. During the unconditioned response, however, a different pattern was observed with men showing significantly higher brain activations. Conclusions: Our data further support the important contribution of estradiol levels in the activation of brain regions underlying fear learning and extinction. The results highlight the need to document gonadal hormonal levels, menstrual cycle phase as well as oral contraceptive use in women in order to avoid overlooking sex differences when investigating the neurobiology of emotional regulation. C1 [Hwang, Moon Jung; Zsido, Rachel G.; Song, Huijin; Pace-Schott, Edward F.; Lebron-Milad, Kelimer; Marin, Marie-France; Milad, Mohammed R.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02129 USA. [Hwang, Moon Jung; Zsido, Rachel G.; Song, Huijin; Pace-Schott, Edward F.; Lebron-Milad, Kelimer; Marin, Marie-France; Milad, Mohammed R.] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Miller, Karen Klahr] Massachusetts Gen Hosp, Dept Med, Dept Neuroendocrine Unit, Boston, MA 02114 USA. [Miller, Karen Klahr] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Milad, MR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, CNY 149,13th St,Room 2508, Boston, MA 02129 USA. EM milad@nmr.mgh.harvard.edu FU National Institute of Mental Health (NIMH) [1R01MH097880-001] FX This study was funded by National Institute of Mental Health (NIMH) 1R01MH097880-001 to M.R.M. The authors would like to thank the members of the MGH Behavioral Neuroscience Program for their helpful comments on the manuscript. NR 43 TC 5 Z9 5 U1 3 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-244X J9 BMC PSYCHIATRY JI BMC Psychiatry PD NOV 18 PY 2015 VL 15 AR 295 DI 10.1186/s12888-015-0673-9 PG 12 WC Psychiatry SC Psychiatry GA CX3EO UT WOS:000365578900001 PM 26581193 ER PT J AU Bjorkbom, A Lelyveld, VS Zhang, SL Zhang, WC Tam, CP Blain, JC Szostak, JW AF Bjorkbom, Anders Lelyveld, Victor S. Zhang, Shenglong Zhang, Weicheng Tam, Chun Pong Blain, J. Craig Szostak, Jack W. TI Bidirectional Direct Sequencing of Noncanonical RNA by Two-Dimensional Analysis of Mass Chromatograms SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID ELECTROSPRAY-IONIZATION; LIQUID-CHROMATOGRAPHY; RIBONUCLEIC-ACIDS; NUCLEIC-ACIDS; SPECTROMETRY; OLIGONUCLEOTIDES; IDENTIFICATION; INTERFERENCE; RESOLUTION; DISCOVERY AB Mass spectrometry (MS) is a powerful technique for characterizing noncanonical nucleobases and other chemical modifications in small RNAs, yielding rich chemical information that is complementary to high-throughput indirect sequencing. However, mass spectra are often prohibitively complex when fragment ions are analyzed following either solution phase hydrolysis or gas phase fragmentation. For all but the simplest cases, ions arising from multiple fragmentation events, alternative fragmentation pathways, and diverse salt adducts frequently obscure desired single-cut fragment ions. Here we show that it is possible to take advantage of predictable regularities in liquid chromatographic (LC) separation of optimized RNA digests to greatly simplify the interpretation of complex MS data. A two-dimensional analysis of extracted compound chromatograms permits straightforward and robust de novo sequencing, using a novel Monte Carlo algorithm that automatically generates bidirectional paired-end reads, pinpointing the position of modified nucleotides in a sequence. We demonstrate that these advances permit routine LCMS sequencing of RNAs containing noncanonical nucleotides, and we furthermore examine the applicability of this approach to the study of oligonucleotides containing artificial modifications as well as those commonly observed in post-transcriptionally modified RNAs. C1 [Bjorkbom, Anders; Lelyveld, Victor S.; Zhang, Shenglong; Zhang, Weicheng; Tam, Chun Pong; Blain, J. Craig; Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. [Bjorkbom, Anders; Lelyveld, Victor S.; Zhang, Shenglong; Zhang, Weicheng; Tam, Chun Pong; Blain, J. Craig; Szostak, Jack W.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Zhang, Weicheng; Tam, Chun Pong; Szostak, Jack W.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Bjorkbom, Anders; Lelyveld, Victor S.; Szostak, Jack W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Bjorkbom, Anders] Abo Akad Univ, Dept Biosci, FI-20520 Turku, Finland. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, 185 Cambridge St, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu FU Simons Foundation [290363]; Academy of Finland FX We thank Drs. L. Li, and C. Hentrich for helpful discussions. This work was supported in part by a grant (290363) from the Simons Foundation to J.W.S. AB. is supported by a fellowship from the Academy of Finland. J.W.S. is an investigator of the Howard Hughes Medical Institute. NR 42 TC 3 Z9 3 U1 3 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD NOV 18 PY 2015 VL 137 IS 45 BP 14430 EP 14438 DI 10.1021/jacs.5b09438 PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA CW6ZV UT WOS:000365148500029 PM 26495937 ER PT J AU Miller, MA Gadde, S Pfirschke, C Engblom, C Sprachman, MM Kohler, RH Yang, KS Laughney, AM Wojtkiewicz, G Kamaly, N Bhonagiri, S Pittet, MJ Farokhzad, OC Weissleder, R AF Miller, Miles A. Gadde, Suresh Pfirschke, Christina Engblom, Camilla Sprachman, Melissa M. Kohler, Rainer H. Yang, Katherine S. Laughney, Ashley M. Wojtkiewicz, Gregory Kamaly, Nazila Bhonagiri, Sushma Pittet, Mikael J. Farokhzad, Omid C. Weissleder, Ralph TI Predicting therapeutic nanomedicine efficacy using a companion magnetic resonance imaging nanoparticle SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID IN-VIVO; DRUG-DELIVERY; LIPOSOMAL DOXORUBICIN; VASCULAR-PERMEABILITY; LUNG-CANCER; CELL; TUMORS; SIZE; ACCUMULATION; FERUMOXYTOL AB Therapeutic nanoparticles (TNPs) have shown heterogeneous responses in human clinical trials, raising questions of whether imaging should be used to identify patients with a higher likelihood of NP accumulation and thus therapeutic response. Despite extensive debate about the enhanced permeability and retention (EPR) effect in tumors, it is increasingly clear that EPR is extremely variable; yet, little experimental data exist to predict the clinical utility of EPR and its influence on TNP efficacy. We hypothesized that a 30-nm magnetic NP (MNP) in clinical use could predict colocalization of TNPs by magnetic resonance imaging (MRI). To this end, we performed single-cell resolution imaging of fluorescently labeled MNPs and TNPs and studied their intratumoral distribution in mice. MNPs circulated in the tumor microvasculature and demonstrated sustained uptake into cells of the tumor microenvironment within minutes. MNPs could predictably demonstrate areas of colocalization for a model TNP, poly(D,L-lactic-co-glycolic acid)-b-polyethylene glycol (PLGA-PEG), within the tumor microenvironment with >85% accuracy and circulating within the microvasculature with >95% accuracy, despite their markedly different sizes and compositions. Computational analysis of NP transport enabled predictive modeling of TNP distribution based on imaging data and identified key parameters governing intratumoral NP accumulation and macrophage uptake. Finally, MRI accurately predicted initial treatment response and drug accumulation in a preclinical efficacy study using a paclitaxel-encapsulated NP in tumor-bearing mice. These approaches yield valuable insight into the in vivo kinetics of NP distribution and suggest that clinically relevant imaging modalities and agents can be used to select patients with high EPR for treatment with TNPs. C1 [Miller, Miles A.; Pfirschke, Christina; Engblom, Camilla; Sprachman, Melissa M.; Kohler, Rainer H.; Yang, Katherine S.; Laughney, Ashley M.; Wojtkiewicz, Gregory; Pittet, Mikael J.; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Ctr Syst Biol, Sch Med, Boston, MA 02114 USA. [Miller, Miles A.; Kohler, Rainer H.; Pittet, Mikael J.; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med, Boston, MA 02114 USA. [Gadde, Suresh; Kamaly, Nazila; Bhonagiri, Sushma; Farokhzad, Omid C.] Harvard Univ, Brigham & Womens Hosp, Dept Anesthesiol, Lab Nanomed & Biomat,Sch Med, Boston, MA 02115 USA. [Farokhzad, Omid C.] King Abdulaziz Univ, Jeddah 21413, Saudi Arabia. [Weissleder, Ralph] Harvard Univ, Dept Syst Biol, Sch Med, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Syst Biol, Sch Med, Boston, MA 02114 USA. EM ofarokhzad@bwh.harvard.edu; rweissleder@mgh.harvard.edu RI Gadde, Suresh/B-9483-2012; Kamaly, Nazila/B-6791-2016 OI Gadde, Suresh/0000-0001-9102-3029; Kamaly, Nazila/0000-0002-9716-5121 FU NIH [R01CA164448, U54-CA151884, 5P50CA086355, HL084312]; DoD [PC140318]; David H. Koch-Prostate Cancer Foundation Award in Nanotherapeutics; Deutsche Forschungsgemeinschaft (DFG) [PF809/1-1]; [T32 CA 79443] FX This work was supported in part by the NIH (R01CA164448, U54-CA151884, 5P50CA086355, and HL084312), DoD (PC140318), and the David H. Koch-Prostate Cancer Foundation Award in Nanotherapeutics. M. A. M. was supported by T32 CA 79443. C. P. is in part supported by Deutsche Forschungsgemeinschaft (DFG) PF809/1-1. NR 38 TC 21 Z9 21 U1 11 U2 42 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD NOV 18 PY 2015 VL 7 IS 314 AR 314ra183 DI 10.1126/scitranslmed.aac6522 PG 12 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA CW8GU UT WOS:000365238300005 PM 26582898 ER PT J AU Liberman, MC Liberman, LD Maison, SF AF Liberman, M. Charles Liberman, Leslie D. Maison, Stephane F. TI Chronic Conductive Hearing Loss Leads to Cochlear Degeneration SO PLOS ONE LA English DT Article ID STEM AUDITORY NUCLEI; CHRONIC OTITIS-MEDIA; BRAIN-STEM; TYMPANIC-MEMBRANE; OLIVOCOCHLEAR INNERVATION; AFFERENT INFLUENCES; SYNAPTIC RIBBONS; SERIAL SECTIONS; ACOUSTIC INJURY; OLDER-ADULTS AB Synapses between cochlear nerve terminals and hair cells are the most vulnerable elements in the inner ear in both noise-induced and age-related hearing loss, and this neuropathy is exacerbated in the absence of efferent feedback from the olivocochlear bundle. If age-related loss is dominated by a lifetime of exposure to environmental sounds, reduction of acoustic drive to the inner ear might improve cochlear preservation throughout life. To test this, we removed the tympanic membrane unilaterally in one group of young adult mice, removed the olivocochlear bundle in another group and compared their cochlear function and innervation to age-matched controls one year later. Results showed that tympanic membrane removal, and the associated threshold elevation, was counterproductive: cochlear efferent innervation was dramatically reduced, especially the lateral olivocochlear terminals to the inner hair cell area, and there was a corresponding reduction in the number of cochlear nerve synapses. This loss led to a decrease in the amplitude of the suprathreshold cochlear neural responses. Similar results were seen in two cases with conductive hearing loss due to chronic otitis media. Outer hair cell death was increased only in ears lacking medial olivocochlear innervation following olivocochlear bundle cuts. Results suggest the novel ideas that 1) the olivocochlear efferent pathway has a dramatic use-dependent plasticity even in the adult ear and 2) a component of the lingering auditory processing disorder seen in humans after persistent middle-ear infections is cochlear in origin. C1 [Liberman, M. Charles; Maison, Stephane F.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Liberman, M. Charles; Liberman, Leslie D.; Maison, Stephane F.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Liberman, M. Charles; Maison, Stephane F.] Harvard Program Speech & Hearing Biosci & Technol, Boston, MA USA. RP Maison, SF (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. EM stephane_maison@meei.harvard.edu FU National Institute on Deafness and Other Communication Disorders (NIDCD) [R01 DC 0188, P30 DC 05209] FX The research was supported by grants from the National Institute on Deafness and Other Communication Disorders (NIDCD): R01 DC 0188 (MCL) and P30 DC 05209 (MCL) (http://www.nidcd.nih.gov/Pages/default.aspx). NR 62 TC 3 Z9 3 U1 1 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 18 PY 2015 VL 10 IS 11 AR e0142341 DI 10.1371/journal.pone.0142341 PG 18 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW7CD UT WOS:000365154600046 PM 26580411 ER PT J AU Traverso, G Ciccarelli, G Schwartz, S Hughes, T Boettcher, T Barman, R Langer, R Swiston, A AF Traverso, G. Ciccarelli, G. Schwartz, S. Hughes, T. Boettcher, T. Barman, R. Langer, R. Swiston, A. TI Physiologic Status Monitoring via the Gastrointestinal Tract SO PLOS ONE LA English DT Article ID CORE TEMPERATURE; SYSTEM; PHONOCARDIOGRAM; VALIDATION; EXTRACTION AB Reliable, real-time heart and respiratory rates are key vital signs used in evaluating the physiological status in many clinical and non-clinical settings. Measuring these vital signs generally requires superficial attachment of physically or logistically obtrusive sensors to subjects that may result in skin irritation or adversely influence subject performance. Given the broad acceptance of ingestible electronics, we developed an approach that enables vital sign monitoring internally from the gastrointestinal tract. Here we report initial proof-of-concept large animal (porcine) experiments and a robust processing algorithm that demonstrates the feasibility of this approach. Implementing vital sign monitoring as a stand-alone technology or in conjunction with other ingestible devices has the capacity to significantly aid telemedicine, optimize performance monitoring of athletes, military service members, and first-responders, as well as provide a facile method for rapid clinical evaluation and triage. C1 [Traverso, G.; Barman, R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol, Boston, MA USA. [Traverso, G.; Barman, R.; Langer, R.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Traverso, G.; Barman, R.; Langer, R.] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Ciccarelli, G.; Schwartz, S.; Hughes, T.; Boettcher, T.; Swiston, A.] MIT, Lincoln Lab, Bioengn Syst & Technol, Lexington, MA 02420 USA. RP Langer, R (reprint author), MIT, Dept Chem Engn, Cambridge, MA 02139 USA. EM rlanger@mit.edu; albert.swiston@ll.mit.edu FU Department of the Air Force [FA8721-05-C-0002]; Office of the Assistant Secretary of Defense for Research and Engineering; NIH grant [EB000244, T32DK7191-38-S1] FX The MIT Lincoln Laboratory portion of this work was sponsored by the Department of the Air Force under Air Force Contract #FA8721-05-C-0002. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the United States Government. The MIT Campus portion of this work was sponsored by the Office of the Assistant Secretary of Defense for Research and Engineering. This work was funded in part by NIH grant EB000244 (to R.L.) and NIH grant T32DK7191-38-S1 (to G.T.).; The MIT Lincoln Laboratory portion of this work was sponsored by the Department of the Air Force under Air Force Contract #FA8721-05-C-0002. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the United States Government. The MIT Campus portion of this work was sponsored by the Office of the Assistant Secretary of Defense for Research and Engineering. This work was funded in part by NIH grant EB000244 (to R.L.) and NIH grant T32DK7191-38-S1 (to G.T.). We would like to thank Pentax for providing the endoscopic equipment used for this research, and in particular Mr. Mike Fina for facilitating access to the equipment. We also thank Kari Siegle for her excellent graphics support, and Monica Siddalls and Robert Marini for their excellent veterinary support. NR 19 TC 1 Z9 1 U1 2 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 18 PY 2015 VL 10 IS 11 AR e0141666 DI 10.1371/journal.pone.0141666 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW7CD UT WOS:000365154600018 PM 26580216 ER PT J AU Hedgpeth, DC Zhang, XM Jin, JF Leite, RS Krayer, JW Huang, Y AF Hedgpeth, Dustin C. Zhang, Xiaoming Jin, Junfei Leite, Renata S. Krayer, Joe W. Huang, Yan TI Periodontal CD14 mRNA expression is downregulated in patients with chronic periodontitis and type 2 diabetes SO BMC ORAL HEALTH LA English DT Article DE Periodontitis; CD14; TLR4; Diabetes; Gene expression ID MATRIX METALLOPROTEINASE-1 EXPRESSION; TOLL-LIKE RECEPTORS; UP-REGULATION; CARDIOVASCULAR-DISEASE; BINDING-PROTEIN; LIPOPOLYSACCHARIDE; TLR4; LPS; INFLAMMATION; ENDOTOXIN AB Background: Patients with type 2 diabetes mellitus (T2DM) have increased severity of periodontitis. Toll-like receptor (TLR) 4, its co-receptors CD14 and MD-2, and adaptor MyD88 play pivotal roles in lipopolysaccharide (LPS)-triggered tissue inflammation and periodontitis. This study investigated the effects of T2DM and periodontitis on TLR4, CD14, MD-2 and MyD88 mRNA expression in surgically removed periodontal tissues. Methods: Periodontal tissue specimens were collected from 14 patients without periodontitis and T2DM (Group 1), 15 patients with periodontitis alone (Group 2), and 7 patients with both periodontitis and T2DM (Group 3). The mRNA of TLR4, CD14, MD-2 and MyD88 was quantified using real-time PCR and compared between the groups. Results: Statistical analysis showed that periodontal expression of CD14 mRNA was significantly reduced across Groups 1, 2 and 3 (p = 0.02) whereas the mRNA expression of TLR4, MD-2 and MyD88 was not significantly different among the groups. Furthermore, when patients in Groups 1 and 2 were combined (n = 22), the CD14 mRNA expression was significantly lower than that in patients of Group 1 (p = 0.04). Conclusions: CD14 mRNA expression was downregulated across patients with neither periodontitis nor T2DM, patients with periodontitis alone and patients with both diseases, suggesting that CD14 mRNA expression is associated with a favorable host response or subjected to a negative feedback regulation. C1 [Hedgpeth, Dustin C.; Leite, Renata S.; Krayer, Joe W.] Med Univ S Carolina, James B Edwards Coll Dent Med, Dept Stomatol, Charleston, SC 29425 USA. [Leite, Renata S.] Med Univ S Carolina, James B Edwards Coll Dent Med, Ctr Oral Hlth Res, Charleston, SC 29425 USA. [Zhang, Xiaoming; Jin, Junfei; Huang, Yan] Med Univ S Carolina, Coll Med, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. [Huang, Yan] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. [Jin, Junfei] Guilin Med Univ, Affiliated Hosp, Lab Hepatobiliary & Pancreat Surg, Guilin 541001, Guangxi, Peoples R China. RP Huang, Y (reprint author), Med Univ S Carolina, Coll Med, Dept Med, Div Endocrinol Diabet & Med Genet, 114 Doughty St, Charleston, SC 29425 USA. EM huangyan@musc.edu FU National Institute of Dental and Craniofacial Research (NIDCR)/National Institutes of Health (NIH) [DE016353]; Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development [5I01BX000854] FX This work was supported by National Institute of Dental and Craniofacial Research (NIDCR)/National Institutes of Health (NIH) grant DE016353 and Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development grant 5I01BX000854 (to Y.H.). NR 47 TC 0 Z9 0 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6831 J9 BMC ORAL HEALTH JI BMC Oral Health PD NOV 18 PY 2015 VL 15 AR 145 DI 10.1186/s12903-015-0118-3 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CW4ZM UT WOS:000365005200001 PM 26581717 ER PT J AU Torres, CG Renfrew, M Kenst, K Tan-McGrory, A Betancourt, JR Lopez, L AF Torres, Carlos G. Renfrew, Megan Kenst, Karey Tan-McGrory, Aswita Betancourt, Joseph R. Lopez, Lenny TI Improving transgender health by building safe clinical environments that promote existing resilience: Results from a qualitative analysis of providers SO BMC PEDIATRICS LA English DT Article DE Transgender health; LGBT health; LGBT youth; Transgender youth; Health disparities; Resilience ID CHILDREN; YOUTH; RISK; CARE; ADOLESCENTS; BARRIERS; PARENTS; NEEDS AB Background: Transgender (TG) individuals experience discordance between their sex at birth and their gender identity. To better understand the health care needs and characteristics of TG youth that contribute to resilience, we conducted a qualitative study with clinical and non-clinical providers. Methods: In-depth interviews were conducted of providers (n = 11) of TG youth (ages 13-21). Convenience and purposive sampling were used to recruit participants in the Boston area. All interviews were audio-recorded and transcribed verbatim. An interview guide of 14 open-ended questions was used to guide the discussion. A grounded theory approach was utilized to code and analyze the data, including double-coding to address issues of inter-rater reliability. Results: Five primary themes emerged: 1) resilience of TG youth 2) lack of access to services that influence health, 3) the critical role of social support, 4) challenges in navigating the health care system, and 5) the need for trans-affirming competency training for providers and frontline staff. Conclusion: The findings of this study show that providers recognize multiple barriers and challenges in the care of TG youth. However, they also identify the resilience exhibited by many youth. We propose that providers can further enhance the resilience of TG youth and help them flourish by offering them necessary resources via the creation of safe and welcoming clinical environments. C1 [Torres, Carlos G.; Betancourt, Joseph R.; Lopez, Lenny] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Renfrew, Megan; Betancourt, Joseph R.; Lopez, Lenny] Partners HealthCare, Boston, MA USA. [Kenst, Karey; Tan-McGrory, Aswita; Betancourt, Joseph R.; Lopez, Lenny] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kenst, Karey; Tan-McGrory, Aswita; Betancourt, Joseph R.; Lopez, Lenny] Massachusetts Gen Hosp, Dispar Solut Ctr, Boston, MA 02114 USA. [Lopez, Lenny] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. RP Lopez, L (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM lopezlenny77@gmail.com FU Scholars in Medicine Office at Harvard Medical School; Robert Wood Johnson Foundation; NIDDK [1K23DK098280-01] FX The authors thank all participants who contributed to this study. We greatly appreciated your help, effort, and valuable contribution to our research. This study was supported by a grant from the Scholars in Medicine Office at Harvard Medical School. Dr. Lenny Lopez also acknowledges the support of the Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Program and NIDDK 1K23DK098280-01 NR 38 TC 0 Z9 0 U1 1 U2 19 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2431 J9 BMC PEDIATR JI BMC Pediatr. PD NOV 18 PY 2015 VL 15 AR 187 DI 10.1186/s12887-015-0505-6 PG 10 WC Pediatrics SC Pediatrics GA CW6BT UT WOS:000365082900001 PM 26577820 ER PT J AU Egorova, N Park, J Orr, SP Kirsch, I Gollub, RL Kong, J AF Egorova, Natalia Park, Joel Orr, Scott P. Kirsch, Irving Gollub, Randy L. Kong, Jian TI Not seeing or feeling is still believing: conscious and non-conscious pain modulation after direct and observational learning SO SCIENTIFIC REPORTS LA English DT Article ID SKIN-CONDUCTANCE RESPONSES; VICARIOUS INSTIGATION; CINGULATE CORTEX; PLACEBO; EMPATHY; HYPERALGESIA; OTHERS; AROUSAL; FEAR AB Our experience with the world is shaped not only directly through personal exposure but also indirectly through observing others and learning from their experiences. Using a conditioning paradigm, we investigated how directly and observationally learned information can affect pain perception, both consciously and non-consciously. Differences between direct and observed cues were manifest in higher pain ratings and larger skin conductance responses to directly experienced cues. However, the pain modulation effects produced by conditioning were of comparable magnitude for direct and observational learning. These results suggest that social observation can induce positive and negative pain modulation. Importantly, the fact that cues learned by observation and activated non-consciously still produced a robust conditioning effect that withstood extinction highlights the role of indirect exposure in placebo and nocebo effects. C1 [Egorova, Natalia; Park, Joel; Orr, Scott P.; Gollub, Randy L.; Kong, Jian] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02138 USA. [Kirsch, Irving] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Program Placebo Studies & Therapeut Encounter, Boston, MA 02215 USA. RP Kong, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02138 USA. EM jkong@nmr.mgh.harvard.edu OI Egorova, Natalia/0000-0002-9244-2900 FU NIH [R01AT006364, R01AT008563, R01AT0005280, PO1AT006663] FX This work was supported by NIH R01AT006364 and R01AT008563 ( NCCIH) to Jian Kong, NIH R01AT0005280 to Randy L. Gollub and PO1AT006663 to Bruce Rosen and Randy Gollub. We would like to thank Kalliroi Retzepi, Daniel Ott, Xiaoyan Chen, Domenic Minicucci for help in video preparation and to Rongjun Yu for preparing the visual stimuli. NR 41 TC 2 Z9 2 U1 3 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD NOV 18 PY 2015 VL 5 AR 16809 DI 10.1038/srep16809 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW3OR UT WOS:000364902100001 PM 26578164 ER PT J AU Velazquez, ER Meier, R Dunn, WD Alexander, B Wiest, R Bauer, S Gutman, DA Reyes, M Aerts, HJWL AF Velazquez, Emmanuel Rios Meier, Raphael Dunn, William D., Jr. Alexander, Brian Wiest, Roland Bauer, Stefan Gutman, David A. Reyes, Mauricio Aerts, Hugo J. W. L. TI Fully automatic GBM segmentation in the TCGA-GBM dataset: Prognosis and correlation with VASARI features SO SCIENTIFIC REPORTS LA English DT Article ID QUANTITATIVE VOLUMETRIC-ANALYSIS; HIGH-GRADE GLIOMAS; GLIOBLASTOMA-MULTIFORME; GENE-EXPRESSION; BRAIN-TUMOR; SURVIVAL; IMAGES; IDENTIFICATION; INFORMATION; RADIOMICS AB Reproducible definition and quantification of imaging biomarkers is essential. We evaluated a fully automatic MR-based segmentation method by comparing it to manually defined sub-volumes by experienced radiologists in the TCGA-GBM dataset, in terms of sub-volume prognosis and association with VASARI features. MRI sets of 109 GBM patients were downloaded from the Cancer Imaging archive. GBM sub-compartments were defined manually and automatically using the Brain Tumor Image Analysis (BraTumIA). Spearman's correlation was used to evaluate the agreement with VASARI features. Prognostic significance was assessed using the C-index. Auto-segmented sub-volumes showed moderate to high agreement with manually delineated volumes (range (r): 0.4-0.86). Also, the auto and manual volumes showed similar correlation with VASARI features (auto r = 0.35, 0.43 and 0.36; manual r = 0.17, 0.67, 0.41, for contrast-enhancing, necrosis and edema, respectively). The auto-segmented contrast-enhancing volume and post-contrast abnormal volume showed the highest AUC (0.66, CI: 0.55-0.77 and 0.65, CI: 0.54-0.76), comparable to manually defined volumes (0.64, CI: 0.53-0.75 and 0.63, CI: 0.52-0.74, respectively). BraTumIA and manual tumor sub-compartments showed comparable performance in terms of prognosis and correlation with VASARI features. This method can enable more reproducible definition and quantification of imaging based biomarkers and has potential in high-throughput medical imaging research. C1 [Velazquez, Emmanuel Rios; Alexander, Brian; Aerts, Hugo J. W. L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. [Velazquez, Emmanuel Rios; Alexander, Brian; Aerts, Hugo J. W. L.] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Aerts, Hugo J. W. L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol,Dana Farber Canc Inst, Boston, MA 02115 USA. [Aerts, Hugo J. W. L.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Meier, Raphael; Bauer, Stefan; Reyes, Mauricio] Univ Bern, Inst Surg Technol & Biomech, CH-3012 Bern, Switzerland. [Dunn, William D., Jr.; Gutman, David A.] Emory Univ, Sch Med, Dept Biomed Informat, Atlanta, GA USA. [Wiest, Roland; Bauer, Stefan] Univ Bern, Inselspital, Univ Hosp, Support Ctr Adv Neuroimaging,Inst Diagnost & Inte, CH-3010 Bern, Switzerland. [Wiest, Roland; Bauer, Stefan] Univ Bern, Bern, Switzerland. RP Velazquez, ER (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. EM Emmanuel_Rios@dfci.harvard.edu; Hugo_Aerts@dfci.harvard.edu RI Aerts, Hugo/P-6350-2015 OI Aerts, Hugo/0000-0002-2122-2003 FU National Institute of Health [NIH-USA U24CA194354, NIH-USA U01CA190234]; Swiss Cancer League; Bernese Cancer League; Swiss National Foundation FX The authors acknowledge financial support from the National Institute of Health (NIH-USA U24CA194354 and NIH-USA U01CA190234). European Project FP7 "CHIC" and grants from the Swiss Cancer League, Bernese Cancer League and Swiss National Foundation. CANCER, QUANTITATIVE IMAGING, AUTOMATIC GBM SEGMENTATION, IMAGING BIOMARKERS NR 36 TC 6 Z9 6 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD NOV 18 PY 2015 VL 5 AR 16822 DI 10.1038/srep16822 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW3OZ UT WOS:000364902900001 ER PT J AU Hwang, JW Egorova, N Yang, XQ Zhang, WY Chen, J Yang, XY Hu, LJ Sun, S Tu, Y Kong, J AF Hwang, J. W. Egorova, N. Yang, X. Q. Zhang, W. Y. Chen, J. Yang, X. Y. Hu, L. J. Sun, S. Tu, Y. Kong, J. TI Subthreshold depression is associated with impaired resting-state functional connectivity of the cognitive control network SO TRANSLATIONAL PSYCHIATRY LA English DT Article ID DEFAULT-MODE NETWORK; MAJOR DEPRESSION; EXECUTIVE CONTROL; RATING-SCALES; DISORDER; SYMPTOMS; DYSFUNCTION; WOMEN; METAANALYSIS; IMPAIRMENTS AB Subthreshold depression (StD) is a prevalent condition associated with social morbidity and increased service utilization, as well as a high risk of developing into a major depressive disorder (MDD). The lack of well-defined diagnostic criteria for StD has limited research on this disorder, with very few brain-imaging studies examining the neurobiology of StD. Yet, identifying the neural pathology of StD has the potential to elucidate risk factors and prognostic markers for major depression and is crucial for developing tailored treatments for patients at mild stages of depression. We investigated resting-state functional connectivity (rs-FC) of the cognitive control network (CCN), known to be dysregulated in MDD, using the bilateral dorsolateral prefrontal cortex (DLPFC) as a seed, focusing on two cohorts of StD subjects (young and middle aged) as well as matched controls. Irrespective of age, we found a significant rs-FC decrease in the CCN of the StD subjects, compared with matched controls, particularly between the DLPFC and the brain regions associated with the representation of self and other mental states (temporo-parietal junction (TPJ) and precuneus), as well as salience detection and orienting (insula). The functional connectivity between the DLPFC and the left TPJ was also associated with depressive symptom scores measured by the Center for Epidemiologic Studies Depression Scale. This finding may shed light on the neural pathology of StD, leading to better understanding of mild stages of depression, its diagnosis and the development of new treatments. C1 [Hwang, J. W.; Yang, X. Q.; Zhang, W. Y.; Chen, J.; Yang, X. Y.; Hu, L. J.; Tu, Y.] Beijing Univ Chinese Med, Sch Acupuncture Moxibust & Tuina, Beijing 100029, Peoples R China. [Hwang, J. W.; Egorova, N.; Sun, S.; Kong, J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. RP Tu, Y (reprint author), Beijing Univ Chinese Med, Sch Acupuncture Moxibust & Tuina, Beijing 100029, Peoples R China. EM tuyab@263.net; kongj@nmr.mgh.harvard.edu OI Egorova, Natalia/0000-0002-9244-2900 FU International Collaboration Research Program at Science and Technology of China [2007DFA30780]; NIH (NCCIH) [R01AT006364, PO1-AT002048, R01AT008563] FX This scientific work was supported by an International Collaboration Research Program at Science and Technology of China (2007DFA30780) Grant to YT. JK is supported by R01AT006364, PO1-AT002048 and R01AT008563 from NIH (NCCIH). We are grateful to Shuang Jiao and Suicheng Xin for their help in designing the study. NR 67 TC 6 Z9 6 U1 4 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 2158-3188 J9 TRANSL PSYCHIAT JI Transl. Psychiatr. PD NOV 17 PY 2015 VL 5 AR e683 DI 10.1038/tp.2015.174 PG 6 WC Psychiatry SC Psychiatry GA DA2ZQ UT WOS:000367666100005 PM 26575224 ER PT J AU Cantaert, T Schickel, JN Bannock, JM Ng, YS Massad, C Oe, T Wu, R Lavoie, A Walter, JE Notarangelo, LD Al-Herz, W Kilic, SS Ochs, HD Nonoyama, S Durandy, A Meffre, E AF Cantaert, Tineke Schickel, Jean-Nicolas Bannock, Jason M. Ng, Yen-Shing Massad, Christopher Oe, Tyler Wu, Renee Lavoie, Aubert Walter, Jolan E. Notarangelo, Luigi D. Al-Herz, Waleed Kilic, Sara Sebnem Ochs, Hans D. Nonoyama, Shigeaki Durandy, Anne Meffre, Eric TI Activation-Induced Cytidine Deaminase Expression in Human B Cell Precursors Is Essential for Central B Cell Tolerance SO IMMUNITY LA English DT Article ID CLASS-SWITCH RECOMBINATION; SOMATIC HYPERMUTATION; V(D)J RECOMBINATION; AID EXPRESSION; DEFICIENCY; MECHANISMS; BCL6; P53; TRANSLOCATIONS; RECEPTORS AB Activation-induced cytidine deaminase (AID), the enzyme- mediating class-switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes, is essential for the removal of developing autoreactive B cells. How AID mediates central B cell tolerance remains unknown. We report that AID enzymes were produced in a discrete population of immature B cells that expressed recombination-activating gene 2 (RAG2), suggesting that they undergo secondary recombination to edit autoreactive antibodies. However, most AID(+) immature B cells lacked anti-apoptotic MCL-1 and were deleted by apoptosis. AID inhibition using lentiviral-encoded short hairpin (sh)RNA in B cells developing in humanized mice resulted in a failure to remove autoreactive clones. Hence, B cell intrinsic AID expression mediates central B cell tolerance potentially through its RAG-coupled genotoxic activity in self-reactive immature B cells. C1 [Cantaert, Tineke; Schickel, Jean-Nicolas; Bannock, Jason M.; Ng, Yen-Shing; Massad, Christopher; Oe, Tyler; Wu, Renee; Meffre, Eric] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06511 USA. [Lavoie, Aubert] CHU Quebec, Div Allergy Immunol, Quebec City, PQ G1V 4G2, Canada. [Walter, Jolan E.] Harvard Univ, Massachusetts Gen Hosp, Pediat Allergy & Immunol, Sch Med, Boston, MA 02114 USA. [Walter, Jolan E.] Harvard Univ, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Sch Med, Boston, MA 02114 USA. [Walter, Jolan E.; Notarangelo, Luigi D.] Boston Childrens Hosp, Div Immunol, Boston, MA 02115 USA. [Al-Herz, Waleed] Kuwait Univ, Fac Med, Dept Pediat, Safat 13110, Kuwait. [Kilic, Sara Sebnem] Uludag Univ, Fac Med, Dept Pediat, TR-16285 Gorukle, Turkey. [Ochs, Hans D.] Univ Washington, Seattle Childrens Res Inst, Seattle, WA 98195 USA. [Ochs, Hans D.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Nonoyama, Shigeaki] Natl Def Med Coll, Dept Pediat, Tokorozawa, Saitama 3598513, Japan. [Durandy, Anne] INSERM, UMR 1163, F-75015 Paris, France. RP Meffre, E (reprint author), Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06511 USA. EM eric.meffre@yale.edu RI Notarangelo, Luigi/F-9718-2016; OI Notarangelo, Luigi/0000-0002-8335-0262; Oe, Tyler/0000-0001-7178-7822 FU NIH-NIAID [AI061093, AI071087, AI082713]; INSERM, CEE EUROPAD-contract 7th Framework Program [201549]; Assiociation Contre le Cancer; Rubicon program, Netherlands Organization for Scientific Research FX We are very much indebted to the patients and their families. We thank Dr. L. Devine and C. Wang for cell sorting, Dr. P. Soulas-Sprauel for kindly providing the pTRIP-Ubi-GFP lentiviral vector for shRNA delivery, Dr. J.C. Delpech for help with immunostainings and Dr. D. Schatz for providing the anti-RAG2 antibodies and discussions. We also thank all the members of the Immunodeficiency Clinic of the Centre Hospitalier de l'Universite Laval. This work was supported by Grant Numbers AI061093, AI071087, and AI082713 from NIH-NIAID (to E.M.) and INSERM, CEE EUROPAD-contract 7th Framework Program (#201549), and Assiociation Contre le Cancer (to A.D.). T.C. received support from the Rubicon program, Netherlands Organization for Scientific Research. NR 55 TC 10 Z9 10 U1 2 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD NOV 17 PY 2015 VL 43 IS 5 BP 884 EP 895 DI 10.1016/j.immuni.2015.10.002 PG 12 WC Immunology SC Immunology GA CZ1DM UT WOS:000366846000010 PM 26546282 ER PT J AU Legoux, FP Lim, JB Cauley, AW Dikiy, S Ertelt, J Mariani, TJ Sparwasser, T Way, SS Moon, JJ AF Legoux, Francois P. Lim, Jong-Baeck Cauley, Andrew W. Dikiy, Stanislav Ertelt, James Mariani, Thomas J. Sparwasser, Tim Way, Sing Sing Moon, James J. TI CD4(+) T Cell Tolerance to Tissue-Restricted Self Antigens Is Mediated by Antigen-Specific Regulatory T Cells Rather Than Deletion SO IMMUNITY LA English DT Article ID THYMIC EPITHELIAL-CELLS; PERIPHERAL TOLERANCE; LISTERIA-MONOCYTOGENES; RESPONSE MAGNITUDE; IMMUNE-RESPONSE; CLONAL DELETION; SELECTION; AIRE; PHENOTYPE; FOXP3(+) AB Deletion of self-antigen-specific T cells during thymic development provides protection from autoimmunity. However, it is unclear how efficiently this occurs for tissue-restricted self antigens, or how immune tolerance is maintained for self-antigen-specific T cells that routinely escape deletion. Here we show that endogenous CD4(+) T cells with specificity for a set of tissue-restricted self antigens were not deleted at all. For pancreatic self antigen, this resulted in an absence of steady-state tolerance, while for the lung and intestine, tolerance was maintained by the enhanced presence of thymically-derived antigen-specific Foxp3(+) regulatory T (Treg) cells. Unlike deletional tolerance, Treg cell-mediated tolerance was broken by successive antigen challenges. These findings reveal that for some tissue-restricted self antigens, tolerance relies entirely on nondeletional mechanisms that are less durable than T cell deletion. This might explain why autoimmunity is often tissue-specific, and it offers a rationale for cancer vaccine strategies targeting tissue-restricted tumor antigens. C1 [Legoux, Francois P.; Lim, Jong-Baeck; Cauley, Andrew W.; Moon, James J.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. [Legoux, Francois P.; Lim, Jong-Baeck; Cauley, Andrew W.; Moon, James J.] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Charlestown, MA 02129 USA. [Legoux, Francois P.; Lim, Jong-Baeck; Cauley, Andrew W.; Moon, James J.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Dikiy, Stanislav] Howard Hughes Med Inst, Ludwig Ctr, New York, NY 10065 USA. [Dikiy, Stanislav] Program Immunol, New York, NY 10065 USA. [Dikiy, Stanislav] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Ertelt, James; Way, Sing Sing] Childrens Hosp Res Fdn, Div Infect Dis, Cincinnati, OH 45229 USA. [Ertelt, James; Way, Sing Sing] Perinatal Inst, Cincinnati, OH 45229 USA. [Ertelt, James; Way, Sing Sing] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Mariani, Thomas J.] Div Neonatol, Rochester, NY 14642 USA. [Mariani, Thomas J.] Pediat Mol & Personalized Med Program, Rochester, NY 14642 USA. [Mariani, Thomas J.] Univ Rochester, Rochester, NY 14642 USA. [Sparwasser, Tim] TWINCORE Ctr Expt & Clin Infect Res, D-30625 Hannover, Germany. RP Moon, JJ (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. EM jjmoon@mgh.harvard.edu OI Dikiy, Stanislav/0000-0002-8287-6561 FU National Institutes of Health [R01 AI100934, R01 AI087830, R21 AI112186, U19 AI095261, P30 DK043351, R01 AI107020]; Burroughs Wellcome Fund; William F. Milton Fund; Philippe Foundation FX We thank L. Yen, A. Han, and J. Im for assistance with mice and tetramers, C. Luo and R. Mylvaganam for assistance with flow cytometry, F. Marangoni for advice on irradiation bone marrow chimeras, M. Byrne for advice on quantitative RT-PCR, M. Jenkins and J. Mclachlan for advice on epitope mapping, B. Fife for advice on pancreas preps, M. Pepper for advice on lung preps, A. Rudensky for support with Foxp3Delta CNS1 mouse experiments, and R. Anthony, T. Mempel, and A. Luster for critical review of the manuscript. This work was supported by the National Institutes of Health (R01 AI100934, R01 AI087830, and R21 AI112186 to S.S.W.; U19 AI095261, P30 DK043351, and R01 AI107020 to J.J.M.), the Burroughs Wellcome Fund (to S.S.W.), the William F. Milton Fund (to J.J.M.), and the Philippe Foundation (to F.P.L.). NR 43 TC 25 Z9 25 U1 5 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD NOV 17 PY 2015 VL 43 IS 5 BP 896 EP 908 DI 10.1016/j.immuni.2015.10.011 PG 13 WC Immunology SC Immunology GA CZ1DM UT WOS:000366846000011 PM 26572061 ER PT J AU Andrabi, R Voss, JE Liang, CH Briney, B Mccoy, LE Wu, CY Wong, CH Poignard, P Burton, DR AF Andrabi, Raiees Voss, James E. Liang, Chi-Hui Briney, Bryan Mccoy, Laura E. Wu, Chung-Yi Wong, Chi-Huey Poignard, Pascal Burton, Dennis R. TI Identification of Common Features in Prototype Broadly Neutralizing Antibodies to HIV Envelope V2 Apex to Facilitate Vaccine Design SO IMMUNITY LA English DT Article ID STRUCTURAL BASIS; V1/V2 DOMAIN; RECOGNITION; GP120; PG16; PG9; EPITOPE; TRIMER; MATURATION; IMMUNOGEN AB Broadly neutralizing antibodies (bnAbs) directed to the V2 apex of the HIV envelope (Env) trimer isolated from individual HIV-infected donors potently neutralize diverse HIV strains, but strategies for designing immunogens to elicit bnAbs have not been identified. Here, we compared four prototypes (PG9, CH01, PGT145, and CAP256.VRC26.09) of V2 apex bnAbs and showed that all recognized a core epitope of basic V2 residues and the glycan-N160. Two prototype bnAbs were derived from VH-germlines that were 99% identical and used a common germline D-gene encoded YYD-motif to interact with the V2-epitope. We identified isolates that were neutralized by inferred germline (iGL) versions of three of the prototype bnAbs. Soluble Env derived from one of these isolates was shown to form a well-ordered Env trimer that could serve as an immunogen to initiate a V2-apex bnAb response. These studies illustrate a strategy to transition from panels of bnAbs to vaccine candidates. C1 [Andrabi, Raiees; Voss, James E.; Liang, Chi-Hui; Briney, Bryan; Mccoy, Laura E.; Poignard, Pascal; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Andrabi, Raiees; Voss, James E.; Liang, Chi-Hui; Briney, Bryan; Mccoy, Laura E.; Poignard, Pascal; Burton, Dennis R.] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA. [Andrabi, Raiees; Voss, James E.; Liang, Chi-Hui; Briney, Bryan; Mccoy, Laura E.; Burton, Dennis R.] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA. [Wu, Chung-Yi; Wong, Chi-Huey] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan. [Burton, Dennis R.] MIT, Massachusetts Gen Hosp, Ragon Inst, Cambridge, MA 02114 USA. [Burton, Dennis R.] Harvard Univ, Boston, MA 02114 USA. RP Burton, DR (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. EM burton@scripps.edu RI poignard, pascal/N-6678-2013 FU International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Consortium (NAC) [SFP2120/2121]; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) [UM1AI100663]; Bill and Melinda Gates Foundation Collaboration; American people through USAID; James and Jessie Minor Chair in Immunology FX We thank, John Mascola, Michel Nussenzweig, James Robinson, Miroslaw K. Gorny, and Susan Zolla-Pazner for providing antibodies directly or through the IAVI Neutralizing Antibody Consortium (Scripps) or NIH AIDS Research and Reference Reagent Program (ARRRP). This work was supported by the International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Consortium (NAC) Grant SFP2120/2121 (to D.R.B.) and Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) Grant UM1AI100663 (to D.R.B.). This study was made possible by the generous support of the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery (CAVD) and the American people through USAID. D.R.B. acknowledges the support of the James and Jessie Minor Chair in Immunology. We thank Christina Corbaci for her help in the preparation of figures. NR 38 TC 30 Z9 30 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD NOV 17 PY 2015 VL 43 IS 5 BP 959 EP 973 DI 10.1016/j.immuni.2015.10.014 PG 15 WC Immunology SC Immunology GA CZ1DM UT WOS:000366846000016 PM 26588781 ER PT J AU Scharschmidt, TC Vasquez, KS Truong, HA Gearty, SV Pauli, ML Nosbaum, A Gratz, IK Otto, M Moon, JJ Liese, J Abbas, AK Fischbach, MA Rosenblum, MD AF Scharschmidt, Tiffany C. Vasquez, Kimberly S. Truong, Hong-An Gearty, Sofia V. Pauli, Mariela L. Nosbaum, Audrey Gratz, Iris K. Otto, Michael Moon, James J. Liese, Jan Abbas, Abul K. Fischbach, Michael A. Rosenblum, Michael D. TI A Wave of Regulatory T Cells into Neonatal Skin Mediates Tolerance to Commensal Microbes SO IMMUNITY LA English DT Article ID INTESTINAL MICROBIOTA; HAIR-FOLLICLES; IMMUNITY; DISEASE; INFLAMMATION; DIVERSITY; INFECTION; RESIDENT; BACTERIA; HOST AB The skin is a site of constant dialog between the immune system and commensal bacteria. However, the molecular mechanisms that allow us to tolerate the presence of skin commensals without eliciting destructive inflammation are unknown. Using a model system to study the antigen-specific response to S. epidermidis, we demonstrated that skin colonization during a defined period of neonatal life was required for establishing immune tolerance to commensal microbes. This crucial window was characterized by an abrupt influx of highly activated regulatory T (Treg) cells into neonatal skin. Selective inhibition of this Treg cell wave completely abrogated tolerance. Thus, the host-commensal relationship in the skin relied on a unique Treg cell population that mediated tolerance to bacterial antigens during a defined developmental window. This suggests that the cutaneous microbiome composition in neonatal life is crucial in shaping adaptive immune responses to commensals, and disrupting these interactions might have enduring health implications. C1 [Scharschmidt, Tiffany C.; Vasquez, Kimberly S.; Truong, Hong-An; Gearty, Sofia V.; Pauli, Mariela L.; Nosbaum, Audrey; Rosenblum, Michael D.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. [Gratz, Iris K.] Salzburg Univ, Dept Mol Biol, A-5020 Salzburg, Austria. [Otto, Michael] NIAID, NIH, Bethesda, MD 20892 USA. [Moon, James J.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Pulm & Crit Care Med, Boston, MA 02129 USA. [Moon, James J.] Harvard Univ, Sch Med, Boston, MA 02129 USA. [Liese, Jan] Univ Tubingen Hosp, Inst Med Microbiol & Hyg, D-72076 Tubingen, Germany. [Abbas, Abul K.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. [Fischbach, Michael A.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA. [Fischbach, Michael A.] Univ Calif San Francisco, Calif Inst Quantitat Biosci, San Francisco, CA 94143 USA. RP Rosenblum, MD (reprint author), Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. EM michael.rosenblum@ucsf.edu RI Gratz, Iris /L-6267-2015; OI Gratz, Iris /0000-0001-7470-7277; Otto, Michael/0000-0002-2222-4115; Scharschmidt, Tiffany/0000-0001-5517-089X FU Diabetes Research Center [NIH P30 DK063720]; NIH [5P30CA082103-15, K08-AR062064, R21-AR066821, DP2-AR068130]; Dermatology Foundation Career Development Award; UCSF Department of Dermatology; Intramural Research Program of the NIH National Institute of Allergy and Infectious Diseases; Burroughs Wellcome Fund [CAMS-1010934]; Scleroderma Research Foundation grant; National Psoriasis Foundation Translational Grant FX We thank C. Benetiz for assistance with animal husbandry and Creative Commons author Seans Potato Business for use of the mouse image in Figures S2 and S4 under the Attribution-ShareAlike license (https://creativecommons.org/licenses/by-sa/3.0/legalcode). Flow-cytometry data were generated in the UCSF Parnassus Flow Cytometry Core, which is supported by the Diabetes Research Center grant NIH P30 DK063720. Histology was performed with assistance from the UCSF Mouse Pathology Core, which is supported by NIH 5P30CA082103-15. T.C.S. is supported by a Dermatology Foundation Career Development Award and the UCSF Department of Dermatology. M.O. is supported by the Intramural Research Program of the NIH National Institute of Allergy and Infectious Diseases. This work was primarily funded by grants to M.D.R.: NIH K08-AR062064, Burroughs Wellcome Fund CAMS-1010934, NIH R21-AR066821, NIH DP2-AR068130, a Scleroderma Research Foundation grant, and a National Psoriasis Foundation Translational Grant. NR 54 TC 25 Z9 26 U1 3 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 EI 1097-4180 J9 IMMUNITY JI Immunity PD NOV 17 PY 2015 VL 43 IS 5 BP 1011 EP 1021 DI 10.1016/j.immuni.2015.10.016 PG 11 WC Immunology SC Immunology GA CZ1DM UT WOS:000366846000020 PM 26588783 ER PT J AU Schottle, J Chatterjee, S Volz, C Siobal, M Florin, A Rokitta, D Hinze, Y Dietlein, F Plenker, D Konig, K Albus, K Heuckmann, JM Rauh, D Franz, T Neumaier, B Fuhr, U Heukamp, LC Ullrich, RT AF Schoettle, Jakob Chatterjee, Sampurna Volz, Caroline Siobal, Maike Florin, Alexandra Rokitta, Dennis Hinze, Yvonne Dietlein, Felix Plenker, Dennis Koenig, Katharina Albus, Kerstin Heuckmann, Johannes M. Rauh, Daniel Franz, Thomas Neumaier, Bernd Fuhr, Uwe Heukamp, Lukas C. Ullrich, Roland T. TI Intermittent high-dose treatment with erlotinib enhances therapeutic efficacy in EGFR-mutant lung cancer SO ONCOTARGET LA English DT Article DE lung cancer; NSCLC; EGFR; erlotinib; high-dose scheduling; PET ID GROWTH-FACTOR RECEPTOR; POSITRON-EMISSION-TOMOGRAPHY; ACQUIRED-RESISTANCE; KINASE INHIBITORS; T790M MUTATIONS; IN-VIVO; GEFITINIB; AMPLIFICATION; ADENOCARCINOMAS; CARBOPLATIN AB Treatment with EGFR kinase inhibitors improves progression-free survival of patients with EGFR-mutant lung cancer. However, all patients with initial response will eventually acquire resistance and die from tumor recurrence. We found that intermittent high-dose treatment with erlotinib induced apoptosis more potently and improved tumor shrinkage significantly than the established low doses. In mice carrying EGFR-mutant xenografts intermittent high-dose treatment (200 mg/kg every other day) was tolerable and prolonged progression-free survival and reduced the frequency of acquired resistance. Intermittent EGFR-targeted high-dose schedules induce more profound as well as sustained target inhibition and may afford enhanced therapeutic efficacy. C1 [Schoettle, Jakob; Chatterjee, Sampurna; Volz, Caroline; Ullrich, Roland T.] Univ Cologne, Dept Internal Med 1, Ctr Integrated Oncol Koln Bonn, D-50931 Cologne, Germany. [Schoettle, Jakob; Chatterjee, Sampurna; Volz, Caroline; Ullrich, Roland T.] Univ Cologne, Ctr Mol Med Cologne ZMMK, D-50931 Cologne, Germany. [Schoettle, Jakob; Chatterjee, Sampurna; Volz, Caroline; Siobal, Maike; Neumaier, Bernd; Ullrich, Roland T.] Max Planck Gesell, Klaus Joachim Zulch Labs, Max Planck Inst Metab, Cologne, Germany. [Schoettle, Jakob; Chatterjee, Sampurna; Volz, Caroline; Siobal, Maike; Neumaier, Bernd; Ullrich, Roland T.] Univ Cologne, Fac Med, D-50931 Cologne, Germany. [Schoettle, Jakob; Dietlein, Felix; Plenker, Dennis] Univ Cologne, Dept Translat Genom, Fac Med, D-50931 Cologne, Germany. [Florin, Alexandra; Koenig, Katharina; Albus, Kerstin; Heukamp, Lukas C.] Univ Cologne, Univ Hosp Med Ctr, Dept Pathol, D-50931 Cologne, Germany. [Rokitta, Dennis; Fuhr, Uwe] Univ Cologne, Univ Hosp Med Ctr, Dept Pharmacol, D-50931 Cologne, Germany. [Hinze, Yvonne; Franz, Thomas] Max Planck Inst Ageing, Cologne, Germany. [Heuckmann, Johannes M.; Heukamp, Lukas C.] NEO New Oncol AG, Cologne, Germany. [Rauh, Daniel] Tech Univ Dortmund, D-44221 Dortmund, Germany. [Neumaier, Bernd] Univ Cologne, IREMB, Univ Hosp Med Ctr, D-50931 Cologne, Germany. [Chatterjee, Sampurna] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Ullrich, RT (reprint author), Univ Cologne, Dept Internal Med 1, Ctr Integrated Oncol Koln Bonn, D-50931 Cologne, Germany. EM roland.ullrich@nf.mpg.de FU Deutsche Forschungsgemeinschaft through SFB832; DFG [UL379/1-1]; Nachwuchsforschungsgruppen-NRW [1411ng005] FX This work was supported by the Deutsche Forschungsgemeinschaft through SFB832 (Z2 to R.T. Ullrich and B. Neumaier; TP6 to R.T. Ullrich; TP5 to L.C. Heukamp; and Z1 to L.C. Heukamp), by the DFG (Grant No.: UL379/1-1 to R.T. Ullrich) and by the Nachwuchsforschungsgruppen-NRW (Grant No.: 1411ng005 to R.T. Ullrich). NR 36 TC 4 Z9 4 U1 0 U2 7 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD NOV 17 PY 2015 VL 6 IS 36 BP 38458 EP 38468 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CY0RS UT WOS:000366114000006 PM 26540572 ER PT J AU Liu, YG Qiang, WA Xu, XF Dong, RF Karst, AM Liu, ZJ Kong, BH Drapkin, RI Wei, JJ AF Liu, Yugang Qiang, Wenan Xu, Xiaofei Dong, Ruifen Karst, Alison M. Liu, Zhaojian Kong, Beihua Drapkin, Ronny I. Wei, Jian-Jun TI Role of miR-182 in response to oxidative stress in the cell fate of human fallopian tube epithelial cells SO ONCOTARGET LA English DT Article DE fallopian tube secretory cells; ROS-induced miRNA (ROSmiR); p53; senescence bypass; tumorigenesis ID SEROUS OVARIAN-CANCER; DNA-DAMAGE RESPONSE; FOLLICULAR-FLUID; TRANSCRIPTION FACTOR; CANDIDATE PRECURSOR; MOUSE MODEL; IN-VIVO; CARCINOMA; PATHOGENESIS; EXPRESSION AB High grade serous ovarian carcinoma (HGSC) is a DNA instable tumor and its precursor is commonly found originating from the fimbriated end of the fallopian tube secretory epithelial (FTSE) cells. The local stresses via ovulation and related inflammation are risks for HGSC. In this study, we examined the cellular and molecular responses of FTSE cells to stress. We found that excess intracellular reactive oxygen species (ROS) in normal FTSE cells upregulated a subset of microRNA expression (defined as ROSmiRs). Most ROSmiRs' expression and function were influenced and regulated by p53, and together they drove the cells into stress-induced premature senescence (SIPS). However, ROS-induced miR-182 is regulated by beta-catenin, not by p53. In normal FTSE cells, miR-182 overexpression triggers cellular senescence by p53-mediated upregulation of p21. Conversely, in cells with p53 mutations, miR-182 overexpression no longer enhances p21 but functions as an "Onco-miR". p53 dysfunction is a prerequisite for miR-182-mediated tumorigenesis. In addition, we found that human follicular fluid could significantly induce intracellular ROS in normal FTSE cells. These findings suggest that ROS and p53 mutations may trigger a series of events, beginning with overexpressing miR-182 by ROS and beta-catenin, impairing the DNA damage response, promoting DNA instability, bypassing senescence and eventually leading to DNA instable tumors in FTSE cells. C1 [Liu, Yugang; Qiang, Wenan; Xu, Xiaofei; Dong, Ruifen; Liu, Zhaojian; Wei, Jian-Jun] Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA. [Qiang, Wenan; Wei, Jian-Jun] Northwestern Univ, Feinberg Sch Med, Dept Obstet & Gynecol, Chicago, IL 60611 USA. [Qiang, Wenan; Wei, Jian-Jun] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Karst, Alison M.; Drapkin, Ronny I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. [Kong, Beihua] Shandong Univ, Qilu Hosp, Dept Obstet & Gynecol, Jinan 250100, Shandong, Peoples R China. RP Wei, JJ (reprint author), Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA. EM jianjun-wei@northwestern.edu RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 FU National Cancer Institute at the National Institutes of Health [R21 CA167038] FX This study was supported by National Cancer Institute at the National Institutes of Health (R21 CA167038 to J.W.). NR 49 TC 3 Z9 3 U1 1 U2 5 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD NOV 17 PY 2015 VL 6 IS 36 BP 38983 EP 38998 PG 16 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CY0RS UT WOS:000366114000042 PM 26472020 ER PT J AU Pindyck, T Prochazka, AV AF Pindyck, Talia Prochazka, Allan V. TI Review: Screening identifies women having intimate partner violence, but effects are unclear SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 [Pindyck, Talia; Prochazka, Allan V.] Denver VA Med Ctr, Aurora, CO USA. RP Pindyck, T (reprint author), Denver VA Med Ctr, Aurora, CO USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 17 PY 2015 VL 163 IS 10 BP JC3 EP JC3 DI 10.7326/ACPJC-2015-163-10-003 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CX5MQ UT WOS:000365746400004 PM 26571257 ER PT J AU Wang, R Stone, RL Kaelber, JT Rochat, RH Nick, AM Vijayan, KV Afshar-Kharghan, V Schmid, MF Dong, JF Sood, AK Chiu, W AF Wang, Rui Stone, Rebecca L. Kaelber, Jason T. Rochat, Ryan H. Nick, Alpa M. Vijayan, K. Vinod Afshar-Kharghan, Vahid Schmid, Michael F. Dong, Jing-Fei Sood, Anil K. Chiu, Wah TI Electron cryotomography reveals ultrastructure alterations in platelets from patients with ovarian cancer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE electron; cryotomography; platelet; microtubule; cancer ID CRYOELECTRON TOMOGRAPHY; TUMOR-METASTASIS; THROMBOCYTOSIS; VISUALIZATION; MICROSCOPY; ACQUISITION; CELLS AB Thrombocytosis and platelet hyperreactivity are known to be associated with malignancy; however, there have been no ultrastructure studies of platelets from patients with ovarian cancer. Here, we used electron cryotomography (cryo-ET) to examine frozen-hydrated platelets from patients with invasive ovarian cancer (n = 12) and control subjects either with benign adnexal mass (n = 5) or free from disease (n = 6). Qualitative inspections of the tomograms indicate significant morphological differences between the cancer and control platelets, including disruption of the microtubule marginal band. Quantitative analysis of subcellular features in 120 platelet electron tomograms from these two groups showed statistically significant differences in mitochondria, as well as microtubules. These structural variations in the platelets from the patients with cancer may be correlated with the altered platelet functions associated with malignancy. Cryo-ET of platelets shows potential as a noninvasive biomarker technology for ovarian cancer and other platelet-related diseases. C1 [Wang, Rui; Rochat, Ryan H.; Schmid, Michael F.; Chiu, Wah] Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Grad Program Struct & Computat Biol & Mol Biophys, Houston, TX 77030 USA. [Wang, Rui; Kaelber, Jason T.; Rochat, Ryan H.; Schmid, Michael F.; Chiu, Wah] Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Natl Ctr Macromol Imaging, Houston, TX 77030 USA. [Stone, Rebecca L.; Nick, Alpa M.; Afshar-Kharghan, Vahid; Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. [Kaelber, Jason T.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Vijayan, K. Vinod] Baylor Coll Med, Michael E DeBakey Vet Affair Med Ctr, Dept Med, Houston, TX 77030 USA. [Dong, Jing-Fei] Michael E DeBakey Vet Affair Med Ctr, Ctr Translat Res Inflammat, Houston, TX 77030 USA. [Dong, Jing-Fei] Univ Washington, Sch Med, Dept Med, Puget Sound Blood Ctr, Seattle, WA 98104 USA. [Dong, Jing-Fei] Univ Washington, Sch Med, Dept Med, Div Hematol, Seattle, WA 98104 USA. [Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA. [Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Ctr RNA Interference & Noncoding RNA, Houston, TX 77030 USA. RP Sood, AK (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. EM asood@mdanderson.org; wah@bcm.edu OI Kaelber, Jason/0000-0001-9426-1030 FU NIH [P41GM103832, HL071895, HL085769, HL081613, CA177909]; Department of Defense [OC120547, OC093416]; Ovarian Cancer Research Fund Program Project Development Grant; Bettyann Asche Murray Distinguished Professorship; Baylor College of Medicine; MD Anderson Cancer Center Collaborative Award FX This research has been supported by NIH Grants P41GM103832, HL071895, HL085769, HL081613, and CA177909; Department of Defense Grants OC120547 and OC093416; an Ovarian Cancer Research Fund Program Project Development Grant; the Bettyann Asche Murray Distinguished Professorship; and a Baylor College of Medicine and MD Anderson Cancer Center Collaborative Award. NR 37 TC 6 Z9 6 U1 2 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 17 PY 2015 VL 112 IS 46 BP 14266 EP 14271 DI 10.1073/pnas.1518628112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW7IA UT WOS:000365170400056 PM 26578771 ER PT J AU Tolaney, SM Boucher, Y Duda, DG Martin, JD Seano, G Ancukiewicz, M Barry, WT Goel, S Lahdenrata, J Isakoff, SJ Yeh, ED Jain, SR Golshan, M Brock, J Snuderl, M Winer, EP Krop, IE Jain, RK AF Tolaney, Sara M. Boucher, Yves Duda, Dan G. Martin, John D. Seano, Giorgio Ancukiewicz, Marek Barry, William T. Goel, Shom Lahdenrata, Johanna Isakoff, Steven J. Yeh, Eren D. Jain, Saloni R. Golshan, Mehra Brock, Jane Snuderl, Matija Winer, Eric P. Krop, Ian E. Jain, Rakesh K. TI Role of vascular density and normalization in response to neoadjuvant bevacizumab and chemotherapy in breast cancer patients SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE antiangiogenic therapy; circulating and tissue biomarkers; PAM50 gene signature; cellular proliferation ID INTERSTITIAL HYPERTENSION; ANTIANGIOGENIC THERAPY; GLIOBLASTOMA PATIENTS; RECTAL-CANCER; PRIMARY TUMOR; PATHOLOGICAL RESPONSE; PREDICT SURVIVAL; BLOOD PERFUSION; PHASE-3 TRIAL; SOLID STRESS AB Preoperative bevacizumab and chemotherapy may benefit a subset of breast cancer (BC) patients. To explore potential mechanisms of this benefit, we conducted a phase II study of neoadjuvant bevacizumab (single dose) followed by combined bevacizumab and adriamycin/cyclophosphamide/paclitaxel chemotherapy in HER2-negative BC. The regimen was well-tolerated and showed a higher rate of pathologic complete response (pCR) in triple-negative (TN) BC (11/21 patients or 52%, [95% confidence interval (CI): 30,74]) than in hormone receptor-positive (HR) BC [5/78 patients or 6% (95% CI: 2,14)]. Within the HRBCs, basal-like subtype was significantly associated with pCR (P = 0.007; Fisher exact test). We assessed interstitial fluid pressure (IFP) and tissue biopsies before and after bevacizumab monotherapy and circulating plasma biomarkers at baseline and before and after combination therapy. Bevacizumab alone lowered IFP, but to a smaller extent than previously observed in other tumor types. Pathologic response to therapy correlated with sVEGFR1 postbevacizumab alone in TNBC (Spearman correlation 0.610, P = 0.0033) and pretreatment microvascular density (MVD) in all patients (Spearman correlation 0.465, P = 0.0005). Moreover, increased pericyte-covered MVD, amarker of extent of vascular normalization, after bevacizumab monotherapy was associated with improved pathologic response to treatment, especially in patients with a high pretreatment MVD. These data suggest that bevacizumab prunes vessels while normalizing those remaining, and thus is beneficial only when sufficient numbers of vessels are initially present. This study implicates pretreatment MVD as a potential predictive biomarker of response to bevacizumab in BC and suggests that new therapies are needed to normalize vessels without pruning. C1 [Tolaney, Sara M.; Goel, Shom; Winer, Eric P.; Krop, Ian E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02114 USA. [Tolaney, Sara M.; Boucher, Yves; Duda, Dan G.; Martin, John D.; Seano, Giorgio; Ancukiewicz, Marek; Barry, William T.; Goel, Shom; Lahdenrata, Johanna; Isakoff, Steven J.; Yeh, Eren D.; Jain, Saloni R.; Golshan, Mehra; Brock, Jane; Snuderl, Matija; Winer, Eric P.; Krop, Ian E.; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Boucher, Yves; Duda, Dan G.; Martin, John D.; Seano, Giorgio; Ancukiewicz, Marek; Goel, Shom; Lahdenrata, Johanna; Jain, Saloni R.; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Martin, John D.; Jain, Saloni R.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Barry, William T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02114 USA. [Isakoff, Steven J.] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. [Yeh, Eren D.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02114 USA. [Golshan, Mehra] Brigham & Womens Hosp, Dept Surg, Boston, MA 02114 USA. [Brock, Jane] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02114 USA. [Snuderl, Matija] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Krop, IE (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02114 USA. EM ikrop@partners.org; jain@steele.mgh.harvard.edu RI Martin, John/L-6892-2016; Seano, Giorgio/R-6611-2016; OI Martin, John/0000-0002-9828-8203; Seano, Giorgio/0000-0002-7294-302X; Snuderl, Matija/0000-0003-0752-0917 FU Genentech grant; AVON National Cancer Institute Progress for Patients Program [2P50 CA089393-08S2]; Department of Defense Breast Cancer Research Innovator Award [W81XWH-10-1-0016]; National Cancer Institute [R01CA098706]; Susan G. Komen Foundation [PDF14301739]; Associazione Italiana per la Ricerca sul Cancro Fellowship [13604] FX The authors thank Drs. James Baish, Vikash Chauhan, Kyrre Emblem, Dai Fukumura, Joao Incio, and Triantafyllos Stylianopoulos for their helpful comments on the manuscript and Carolyn Smith for technical assistance. The clinical trial was supported by a Genentech grant (to S.M.T., I.E.K., and E.P.W.) and AVON National Cancer Institute Progress for Patients Program Grant 2P50 CA089393-08S2 (to Dr. Dick J. Iglehart). Correlative studies were funded through Department of Defense Breast Cancer Research Innovator Award W81XWH-10-1-0016 (to R.K.J.), National Cancer Institute Grant R01CA098706 (to Y.B.), Susan G. Komen Foundation Fellowship PDF14301739 (to G.S.), and Associazione Italiana per la Ricerca sul Cancro Fellowship 13604 (to G.S.). NR 56 TC 27 Z9 27 U1 3 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 17 PY 2015 VL 112 IS 46 BP 14325 EP 14330 DI 10.1073/pnas.1518808112 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW7IA UT WOS:000365170400066 PM 26578779 ER PT J AU Sundaravel, S Duggan, R Bhagat, T Ebenezer, DL Liu, H Yu, YT Bartenstein, M Unnikrishnan, M Karmakar, S Liu, TC Torregroza, I Quenon, T Anastasi, J McGraw, KL Pellagatti, A Boultwood, J Yajnik, V Artz, A Le Beau, MM Steidl, U List, AF Evans, T Verma, A Wickrema, A AF Sundaravel, Sriram Duggan, Ryan Bhagat, Tushar Ebenezer, David L. Liu, Hui Yu, Yiting Bartenstein, Matthias Unnikrishnan, Madhu Karmakar, Subhradip Liu, Ting-Chun Torregroza, Ingrid Quenon, Thomas Anastasi, John McGraw, Kathy L. Pellagatti, Andrea Boultwood, Jacqueline Yajnik, Vijay Artz, Andrew Le Beau, Michelle M. Steidl, Ulrich List, Alan F. Evans, Todd Verma, Amit Wickrema, Amittha TI Reduced DOCK4 expression leads to erythroid dysplasia in myelodysplastic syndromes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE erythroid; MDS; DOCK4; signaling; actin ID ACUTE MYELOID-LEUKEMIA; PROGNOSTIC SCORING SYSTEM; PLURIPOTENT STEM-CELLS; PROTEIN-KINASE-C; PROGENITOR CELLS; SIGNALING PATHWAY; TUMOR-SUPPRESSOR; GENE-EXPRESSION; RAC GTPASES; ERYTHROPOIETIN AB Anemia is the predominant clinical manifestation of myelodysplastic syndromes (MDS). Loss or deletion of chromosome 7 is commonly seen in MDS and leads to a poor prognosis. However, the identity of functionally relevant, dysplasia-causing, genes on 7q remains unclear. Dedicator of cytokinesis 4 (DOCK4) is a GTPase exchange factor, and its gene maps to the commonly deleted 7q region. We demonstrate that DOCK4 is underexpressed in MDS bone marrow samples and that the reduced expression is associated with decreased overall survival in patients. We show that depletion of DOCK4 levels leads to erythroid cells with dysplastic morphology both in vivo and in vitro. We established a novel single-cell assay to quantify disrupted F-actin filament network in erythroblasts and demonstrate that reduced expression of DOCK4 leads to disruption of the actin filaments, resulting in erythroid dysplasia that phenocopies the red blood cell (RBC) defects seen in samples from MDS patients. Reexpression of DOCK4 in -7q MDS patient erythroblasts resulted in significant erythropoietic improvements. Mechanisms underlying F-actin disruption revealed that DOCK4 knockdown reduces ras-related C3 botulinum toxin substrate 1 (RAC1) GTPase activation, leading to increased phosphorylation of the actin-stabilizing protein ADDUCIN in MDS samples. These data identify DOCK4 as a putative 7q gene whose reduced expression can lead to erythroid dysplasia. C1 [Sundaravel, Sriram; Duggan, Ryan; Ebenezer, David L.; Liu, Hui; Karmakar, Subhradip; Anastasi, John; Artz, Andrew; Le Beau, Michelle M.; Wickrema, Amittha] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Bhagat, Tushar; Yu, Yiting; Bartenstein, Matthias; Unnikrishnan, Madhu; Steidl, Ulrich; Verma, Amit] Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA. [Liu, Ting-Chun; Torregroza, Ingrid; Quenon, Thomas; Evans, Todd] Weill Cornell Med Coll, Dept Surg, New York, NY 10065 USA. [McGraw, Kathy L.; List, Alan F.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Pellagatti, Andrea; Boultwood, Jacqueline] Univ Oxford, Radcliffe Dept Med, Oxford OX3 9DU, England. [Yajnik, Vijay] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Evans, T (reprint author), Weill Cornell Med Coll, Dept Surg, New York, NY 10065 USA. EM tre2003@med.cornell.edu; amit.verma@einstein.yu.edu; awickrem@medicine.bsd.uchicago.edu OI Bartenstein, Matthias/0000-0002-0908-770X FU NIH [HL16336, HL056183, CA40046]; University of Chicago Comprehensive Cancer Center; Giving Tree Foundation; Harith Foundation; Suhith Wickrema Memorial Cancer Fund; Leukemia & Lymphoma Research of the United Kingdom FX We thank Dr. Velia M. Fowler at the Scripps Research Institute and Dr. Lucy A. Godley for their constructive comments; the personnel in the Flow Cytometry Facility for their expert advice; and Elizabeth M. Davis and Mathew Horch for technical assistance. This work was supported, in part, by NIH Grants HL16336 (to A.V. and A.W.), HL056183 (to T.E.), and CA40046 (to M.M.L.B.); by a University of Chicago Comprehensive Cancer Center Pilot Project Award, the Giving Tree Foundation, Harith Foundation, and Suhith Wickrema Memorial Cancer Fund (A.W.); and by Leukemia & Lymphoma Research of the United Kingdom (A.P. and J.B.). NR 42 TC 2 Z9 2 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 17 PY 2015 VL 112 IS 46 BP E6359 EP E6368 DI 10.1073/pnas.1516394112 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW7IA UT WOS:000365170400015 PM 26578796 ER PT J AU Brucken, A Derwall, M Bleilevens, C Stoppe, C Gotzenich, A Gaisa, NT Weis, J Nolte, KW Rossaint, R Ichinose, F Fries, M AF Bruecken, Anne Derwall, Matthias Bleilevens, Christian Stoppe, Christian Goetzenich, Andreas Gaisa, Nadine T. Weis, Joachim Nolte, Kay Wilhelm Rossaint, Rolf Ichinose, Fumito Fries, Michael TI Brief inhalation of nitric oxide increases resuscitation success and improves 7-day-survival after cardiac arrest in rats: a randomized controlled animal study SO CRITICAL CARE LA English DT Article ID MIGRATION INHIBITORY FACTOR; AMERICAN-HEART-ASSOCIATION; SUCCESSFUL CARDIOPULMONARY-RESUSCITATION; EMERGENCY CARDIOVASCULAR CARE; BRAIN-DAMAGE; INHALED NO; MYOCARDIAL DYSFUNCTION; CLINICAL-OUTCOMES; SURVIVAL; STROKE AB Introduction: Inhaled nitric oxide (iNO) improves outcomes when given post systemic ischemia/reperfusion injury. iNO given during cardiopulmonary resuscitation (CPR) may therefore improve return of spontaneous circulation (ROSC) rates and functional outcome after cardiac arrest (CA). Methods: Thirty male Sprague-Dawley rats were subjected to 10 minutes of CA and at least 3 minutes of CPR. Animals were randomized to receive either 0 (n = 10, Control), 20 (n = 10, 20 ppm), or 40 (n = 10, 40 ppm) ppm iNO during CPR until 30 minutes after ROSC. A neurological deficit score was assessed daily for seven days following the experiment. On day 7, brains, hearts, and blood were sampled for histological and biochemical evaluation. Results: During CPR, 20 ppm iNO significantly increased diastolic arterial pressure (Control: 57 +/- 5.04 mmHg; 20 ppm: 71.57 +/- 57.3 mmHg, p < 0.046) and decreased time to ROSC (Control: 842 +/- 21 s; 20 ppm: 792 +/- 5 s, (p = 0.02)). Thirty minutes following ROSC, 20 ppm iNO resulted in an increase in mean arterial pressure (Control: 83 +/- 4 mmHg; 20 ppm: 98 +/- 4 mmHg, p = 0.035), a less pronounced rise in lactate and inflammatory cytokine levels, and attenuated cardiac damage. Inhalation of NO at 20 ppm improved neurological outcomes in rats 2 to 7 days after CA and CPR. This translated into increases in 7 day survival (Control: 4; 20 ppm: 10; 40 ppm 6, (p = 0.05 20 ppm vs Control and 40 ppm). Conclusions: Our study revealed that breathing NO during CPR markedly improved resuscitation success, 7-day neurological outcomes and survival in a rat model of VF-induced cardiac arrest and CPR. These results support the beneficial effects of NO inhalation after cardiac arrest and CPR. C1 [Bruecken, Anne; Derwall, Matthias; Bleilevens, Christian; Stoppe, Christian; Rossaint, Rolf] Univ Hosp RWTH Aachen, Dept Anesthesiol, D-52074 Aachen, Germany. [Goetzenich, Andreas] Univ Hosp RWTH Aachen, Dept Thorac Cardiac & Vasc Surg, D-52074 Aachen, Germany. [Gaisa, Nadine T.] Univ Hosp RWTH Aachen, Inst Pathol, D-52074 Aachen, Germany. [Weis, Joachim; Nolte, Kay Wilhelm] Univ Hosp RWTH Aachen, Inst Neuropathol, D-52074 Aachen, Germany. [Ichinose, Fumito] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA. [Ichinose, Fumito] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Fries, Michael] St Vincenz Hosp Limburg, Dept Anesthesiol, D-65549 Limburg, Germany. RP Brucken, A (reprint author), Univ Hosp RWTH Aachen, Dept Anesthesiol, Pauwelsstr 30, D-52074 Aachen, Germany. EM abruecken@ukaachen.de OI Stoppe, Christian/0000-0002-2028-2039 NR 56 TC 0 Z9 1 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X EI 1364-8535 J9 CRIT CARE JI Crit. Care PD NOV 17 PY 2015 VL 19 AR 408 DI 10.1186/s13054-015-1128-x PG 13 WC Critical Care Medicine SC General & Internal Medicine GA CW8WM UT WOS:000365280100001 PM 26577797 ER PT J AU Bohula, EA Aylward, PE Bonaca, MP Corbalan, RL Kiss, RG Murphy, SA Scirica, BM White, H Braunwald, E Morrow, DA AF Bohula, Erin A. Aylward, Philip E. Bonaca, Marc P. Corbalan, Ramon L. Kiss, Robert G. Murphy, Sabina A. Scirica, Benjamin M. White, Harvey Braunwald, Eugene Morrow, David A. TI Efficacy and Safety of Vorapaxar With and Without a Thienopyridine for Secondary Prevention in Patients With Previous Myocardial Infarction and No History of Stroke or Transient Ischemic Attack Results from TRA 2 degrees P-TIMI 50 SO CIRCULATION LA English DT Article DE atherosclerosis; receptors; thrombin; thienoypyridine ID ACUTE CORONARY SYNDROMES; ST-SEGMENT ELEVATION; DUAL-ANTIPLATELET THERAPY; ASSOCIATION TASK-FORCE; ATHEROTHROMBOTIC EVENTS; PRACTICE GUIDELINES; AMERICAN-COLLEGE; CLOPIDOGREL; TRIAL; ASPIRIN AB Background-Vorapaxar antagonizes protease-activated receptor 1, the primary receptor for thrombin on human platelets, and reduces recurrent thrombotic events in stable patients with a previous myocardial infarction (MI). We wished to determine whether the efficacy and safety of antiplatelet therapy with vorapaxar was modified by concurrent thienopyridine use. Methods and Results-The Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events-Thrombolysis in Myocardial Infarction 50 (TRA 2 degrees P-TIMI 50) was a randomized, double-blind, placebo-controlled trial of vorapaxar in 26449 patients with previous atherothrombosis. This prespecified analysis included 16897 patients who qualified with a MI in the preceding 2 weeks to 12 months and was restricted to patients without a history of stroke or transient ischemic attack given its contraindication in that population. Randomization was stratified on the basis of planned thienopyridine use. Thienopyridine was planned at randomization in 12410 (73%). Vorapaxar significantly reduced the composite of cardiovascular death, MI, and stroke in comparison with placebo regardless of planned thienopyridine therapy (planned thienopyridine, hazard ratio, 0.80, 0.70-0.91, P<0.001; no planned thienopyridine, hazard ratio, 0.75; 0.60-0.94, P=0.011; P-interaction=0.67). Findings were similar when patients were stratified by actual thienopyridine use at baseline (P-interaction=0.82) and through 18 months (P-interaction=0.44). Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) moderate or severe bleeding risk was increased with vorapaxar and was not significantly altered by planned thienopyridine (planned, hazard ratio, 1.50; 1.18-1.89, P<0.001; no planned, hazard ratio, 1.90, 1.17-3.07, P=0.009; P-interaction=0.37) or actual thienopyridine use (P-interaction=0.24). Conclusions-Vorapaxar reduced cardiovascular death, MI, or stroke in stable patients with a history of previous MI, whether treated concomitantly with a thienopyridine or not. The relative risk of moderate or severe bleeding was similarly increased irrespective of thienopyridine use. C1 [Bohula, Erin A.; Bonaca, Marc P.; Murphy, Sabina A.; Scirica, Benjamin M.; Braunwald, Eugene; Morrow, David A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div,Dept Med, Boston, MA 02115 USA. [Aylward, Philip E.] Flinders Cardiovasc Ctr, Dept Cardiovasc Med, Adelaide, SA, Australia. [Corbalan, Ramon L.] Pontificia Univ Catolica Chile, Div Cardiovasc, Santiago, Chile. [Kiss, Robert G.] Mil Hosp, Dept Cardiol, Budapest, Hungary. [White, Harvey] Auckland City Hosp, Green Lane Cardiovasc Res Unit, Auckland, New Zealand. RP Bohula, EA (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 350 Longwood Ave,First Off Floor, Boston, MA 02115 USA. EM ebohula@partners.org FU Merck and Co. FX The TRA2 degrees P-TIMI 50 Trial was sponsored by Merck and Co. NR 21 TC 11 Z9 12 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 17 PY 2015 VL 132 IS 20 BP 1871 EP 1879 DI 10.1161/CIRCULATIONAHA.114.015042 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CV9UI UT WOS:000364632100005 PM 26338971 ER PT J AU Sager, HB Heidt, T Hulsmans, M Dutta, P Courties, G Sebas, M Wojtkiewicz, GR Tricot, B Iwamoto, Y Sun, Y Weissleder, R Libby, P Swirski, FK Nahrendorf, M AF Sager, Hendrik B. Heidt, Timo Hulsmans, Maarten Dutta, Partha Courties, Gabriel Sebas, Matthew Wojtkiewicz, Gregory R. Tricot, Benoit Iwamoto, Yoshiko Sun, Yuan Weissleder, Ralph Libby, Peter Swirski, Filip K. Nahrendorf, Matthias TI Targeting Interleukin-1 beta Reduces Leukocyte Production After Acute Myocardial Infarction SO CIRCULATION LA English DT Article DE hematopoiesis; hematopoietic stem cells; interleukin-1; myocardial infarction ID HEMATOPOIETIC STEM-CELLS; RECEPTOR ANTAGONIST; PROGENITOR CELLS; HEART-FAILURE; NEURAL STEM; ACUTE-PHASE; IN-VIVO; MICE; ATHEROSCLEROSIS; MACROPHAGES AB Background Myocardial infarction (MI) is an ischemic wound that recruits millions of leukocytes. MI-associated blood leukocytosis correlates inversely with patient survival, yet the signals driving heightened leukocyte production after MI remain incompletely understood. Methods and Results With the use of parabiosis surgery, this study shows that soluble danger signals, among them interleukin-1, increase bone marrow hematopoietic stem cell proliferation after MI. Data obtained in bone marrow reconstitution experiments reveal that interleukin-1 enhances hematopoietic stem cell proliferation by both direct actions on hematopoietic cells and through modulation of the bone marrow's hematopoietic microenvironment. An antibody that neutralizes interleukin-1 suppresses these effects. Anti-interleukin-1 treatment dampens the post-MI increase in hematopoietic stem cell proliferation. Consequently, decreased leukocyte numbers in the blood and infarct reduce inflammation and diminish post-MI heart failure in ApoE(-/-) mice with atherosclerosis. Conclusions The presented insight into post-MI bone marrow activation identifies a mechanistic target for muting inflammation in the ischemically damaged heart. C1 [Sager, Hendrik B.; Heidt, Timo; Hulsmans, Maarten; Dutta, Partha; Courties, Gabriel; Sebas, Matthew; Wojtkiewicz, Gregory R.; Tricot, Benoit; Iwamoto, Yoshiko; Sun, Yuan; Weissleder, Ralph; Swirski, Filip K.; Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Sager, Hendrik B.; Heidt, Timo; Hulsmans, Maarten; Dutta, Partha; Courties, Gabriel; Sebas, Matthew; Wojtkiewicz, Gregory R.; Tricot, Benoit; Iwamoto, Yoshiko; Sun, Yuan; Weissleder, Ralph; Swirski, Filip K.; Nahrendorf, Matthias] Harvard Univ, Sch Med, Boston, MA USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. [Libby, Peter] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. RP Nahrendorf, M (reprint author), Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM mnahrendorf@mgh.harvard.edu FU Novartis; National Institutes of Health [HL117829, HL114477, HL096576, HL080472]; Deutsche Forschungsgemeinschaft [SA1668/2-1, HE-6382/1-1] FX This work was funded in part by grants from Novartis (to Drs Libby, Swirski, and Nahrendorf) and the National Institutes of Health (HL117829, HL114477 and HL096576 to Dr Nahrendorf and HL080472 to Dr Libby). Drs Sager and Heidt were supported by the Deutsche Forschungsgemeinschaft (SA1668/2-1 and HE-6382/1-1). NR 53 TC 17 Z9 17 U1 2 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 17 PY 2015 VL 132 IS 20 BP 1880 EP 1890 DI 10.1161/CIRCULATIONAHA.115.016160 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA CV9UI UT WOS:000364632100006 PM 26358260 ER PT J AU Tong, XJ Hu, ZT Liu, Y Anderson, D Kaplan, JM AF Tong, Xia-Jing Hu, Zhitao Liu, Yu Anderson, Dorian Kaplan, Joshua M. TI A network of autism linked genes stabilizes two pools of synaptic GABA(A) receptors SO ELIFE LA English DT Article ID ELEGANS VULVAL INDUCTION; DE-NOVO MUTATIONS; C. ELEGANS; INHIBITORY SYNAPSES; GLUTAMATERGIC SYNAPSES; AMPA RECEPTORS; QUANTAL TRANSMISSION; ACTIN CYTOSKELETON; DEFICIENT MICE; DIRECT BINDING AB Changing receptor abundance at synapses is an important mechanism for regulating synaptic strength. Synapses contain two pools of receptors, immobilized and diffusing receptors, both of which are confined to post-synaptic elements. Here we show that immobile and diffusing GABA(A) receptors are stabilized by distinct synaptic scaffolds at C. elegans neuromuscular junctions. Immobilized GABA(A) receptors are stabilized by binding to FRM-3/EPB4.1 and LIN-2A/CASK. Diffusing GABA(A) receptors are stabilized by the synaptic adhesion molecules Neurexin and Neuroligin. Inhibitory post-synaptic currents are eliminated in double mutants lacking both scaffolds. Neurexin, Neuroligin, and CASK mutations are all linked to Autism Spectrum Disorders (ASD). Our results suggest that these mutations may directly alter inhibitory transmission, which could contribute to the developmental and cognitive deficits observed in ASD. C1 [Tong, Xia-Jing; Hu, Zhitao; Liu, Yu; Anderson, Dorian; Kaplan, Joshua M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02138 USA. [Tong, Xia-Jing; Hu, Zhitao; Liu, Yu; Anderson, Dorian; Kaplan, Joshua M.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Kaplan, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02138 USA. EM kaplan@molbio.mgh.harvard.edu FU National Institutes of Health (NIH) [R01 NS32196]; Simons Foundation [SF273555] FX National Institutes of Health (NIH) R01 NS32196 Xia-Jing Tong, Zhitao Hu, Dorian Anderson, Joshua M Kaplan; Simons Foundation SF273555 Xia-Jing Tong, Zhitao Hu, Yu Liu, Dorian Anderson, Joshua M Kaplan NR 53 TC 3 Z9 3 U1 7 U2 14 PU ELIFE SCIENCES PUBLICATIONS LTD PI CAMBRIDGE PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND SN 2050-084X J9 ELIFE JI eLife PD NOV 17 PY 2015 VL 4 AR e09648 DI 10.7554/eLife.09648.001 PG 19 WC Biology SC Life Sciences & Biomedicine - Other Topics GA CW2JS UT WOS:000364818800001 PM 26575289 ER PT J AU Boat, TF Buka, SL Perrin, JM AF Boat, Thomas F. Buka, Stephen L. Perrin, James M. TI Children With Mental Disorders Who Receive Disability Benefits A Report From the IOM SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Boat, Thomas F.] Univ Cincinnati, Dept Pediat, Cincinnati, OH USA. [Boat, Thomas F.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Buka, Stephen L.] Brown Univ, Dept Epidemiol, Sch Publ Hlth, Providence, RI 02912 USA. [Perrin, James M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Perrin, James M.] MassGen Hosp Children, Boston, MA USA. RP Boat, TF (reprint author), Cincinnati Childrens Hosp Med Ctr, 3333 Burnet Ave, Cincinnati, OH 45229 USA. EM thomas.boat@cchmc.org NR 6 TC 2 Z9 2 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 17 PY 2015 VL 314 IS 19 BP 2019 EP 2020 DI 10.1001/jama.2015.12445 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CW1PR UT WOS:000364764200011 PM 26361217 ER PT J AU Barry, MJ Hayes, JH AF Barry, Michael J. Hayes, Julia H. TI Evaluating an Elevated Screening PSA Test SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID PROSTATE-SPECIFIC ANTIGEN; CANCER C1 [Barry, Michael J.] Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02114 USA. [Barry, Michael J.] Harvard Univ, Sch Med, Boston, MA USA. [Hayes, Julia H.] Dana Farber Canc Inst, Dept Hematol Oncol, Brighton, MA USA. [Hayes, Julia H.] St Elizabeths Med Ctr, Brighton, MA USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, 50 Staniford St,Ste 802, Boston, MA 02114 USA. EM mbarry@partners.org NR 10 TC 1 Z9 1 U1 3 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 17 PY 2015 VL 314 IS 19 BP 2073 EP 2074 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CW1PR UT WOS:000364764200024 PM 26575065 ER PT J AU Sammon, JD Abdollah, F Choueiri, TK Kantoff, P Nguyen, PL Menon, M Trinh, QD AF Sammon, Jesse D. Abdollah, Firas Choueiri, Toni K. Kantoff, PhilipW. Nguyen, Paul L. Menon, Mani Quoc-Dien Trinh TI Prostate-Specific Antigen Screening After 2012 US Preventive Services Task Force Recommendations SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID CANCER C1 [Sammon, Jesse D.; Quoc-Dien Trinh] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Abdollah, Firas; Menon, Mani] Henry Ford Hlth Syst, VUI Ctr Outcomes Res,Analyt & Evaluat, Detroit, MI USA. [Choueiri, Toni K.; Kantoff, PhilipW.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Nguyen, Paul L.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Sammon, JD (reprint author), Brigham & Womens Hosp, 45 Francis St, Boston, MA 02115 USA. EM jsammon@partners.org NR 5 TC 0 Z9 0 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 17 PY 2015 VL 314 IS 19 BP 2075 EP 2077 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA CW1PR UT WOS:000364764200025 ER PT J AU Pursnani, A Massaro, JM Hoffmann, U AF Pursnani, Amit Massaro, Joseph M. Hoffmann, Udo TI Predicted vs Observed Clinical Event Risk for Cardiovascular Disease Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID CORONARY-ARTERY-DISEASE; OUTCOMES C1 [Pursnani, Amit] NorthShore Univ Hlth Syst, Div Cardiol, Evanston, IL USA. [Massaro, Joseph M.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 100 Charles River Plaza, Boston, MA 02114 USA. EM uhoffmann@mgh.harvard.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 17 PY 2015 VL 314 IS 19 BP 2080 EP 2081 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CW1PR UT WOS:000364764200028 ER PT J AU Bhatt, DL Drozda, JP Shahian, DM Chan, PS Fonarow, GC Heidenreich, PA Jacobs, JP Masoudi, FA Peterson, ED Welke, KF AF Bhatt, Deepak L. Drozda, Joseph P., Jr. Shahian, David M. Chan, Paul S. Fonarow, Gregg C. Heidenreich, Paul A. Jacobs, Jeffrey P. Masoudi, Frederick A. Peterson, Eric D. Welke, Karl F. TI ACC/AHA/STS Statement on the Future of Registries and the Performance Measurement Enterprise SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE ACC/AHA Performance Measures; health policy and outcome research; quality indicators; registries ID QUALITY-OF-CARE; AMERICAN-HEART-ASSOCIATION; ADULT CARDIAC-SURGERY; ACUTE MYOCARDIAL-INFARCTION; PERCUTANEOUS CORONARY INTERVENTION; CARDIOVASCULAR EVENT RATES; TRANSIENT ISCHEMIC ATTACK; BYPASS-GRAFTING SURGERY; TASK-FORCE; HOSPITAL OUTCOMES C1 [Bhatt, Deepak L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Cambridge, MA 02138 USA. [Shahian, David M.] Massachusetts Gen Hosp, Ctr Qual & Safety, Res, Boston, MA 02114 USA. [Chan, Paul S.] Mid Amer Heart Inst, Cardiol, Kansas City, MO 64111 USA. [Fonarow, Gregg C.] Ahmanson UCLA Cardiomyopathy Ctr, Div Cardiol, Los Angeles, CA USA. [Heidenreich, Paul A.] Stanford VA Palo Alto Hlth Care Syst, Med, Stanford, CA USA. [Jacobs, Jeffrey P.] Cardiac Surg Associates, Downers Grove, IL USA. [Masoudi, Frederick A.] Univ Colorado Denver, Div Cardiol, Med, Denver, CO USA. [Peterson, Eric D.] Duke Clin Res Inst, Med, Durham, NC USA. [Welke, Karl F.] Childrens Hosp Illinois, Peoria, IL USA. RP Bhatt, DL (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Cambridge, MA 02138 USA. NR 107 TC 11 Z9 11 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 17 PY 2015 VL 66 IS 20 BP 2230 EP 2245 DI 10.1016/j.jacc.2015.07.010 PG 16 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CV7EH UT WOS:000364434700011 PM 26440214 ER PT J AU Silkoff, PE Strambu, I Laviolette, M Singh, D FitzGerald, JM Lam, S Kelsen, S Eich, A Ludwig-Sengpiel, A Hupp, GC Backer, V Porsbjerg, C Girodet, PO Berger, P Leigh, R Kline, JN Dransfield, M Calhoun, W Hussaini, A Khatri, S Chanez, P Susulic, VS Barnathan, ES Curran, M Das, AM Brodmerkel, C Baribaud, F Loza, MJ AF Silkoff, P. E. Strambu, I. Laviolette, M. Singh, D. FitzGerald, J. M. Lam, S. Kelsen, S. Eich, A. Ludwig-Sengpiel, A. Hupp, G. C. Backer, V. Porsbjerg, C. Girodet, P. O. Berger, P. Leigh, R. Kline, J. N. Dransfield, M. Calhoun, W. Hussaini, A. Khatri, S. Chanez, P. Susulic, V. S. Barnathan, E. S. Curran, M. Das, A. M. Brodmerkel, C. Baribaud, F. Loza, M. J. TI Asthma characteristics and biomarkers from the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) longitudinal profiling study SO RESPIRATORY RESEARCH LA English DT Article DE Asthma; Severity; Phenotypes; Profiling; Biomarkers; Personalized ID EXHALED NITRIC-OXIDE; RESEARCH-PROGRAM; EOSINOPHILIC ASTHMA; PERSISTENT ASTHMA; CLUSTER-ANALYSIS; SPUTUM; INFLAMMATION; PHENOTYPES; ADULTS; LUNG AB Background: Asthma is a heterogeneous disease and development of novel therapeutics requires an understanding of pathophysiologic phenotypes. The purpose of the ADEPT study was to correlate clinical features and biomarkers with molecular characteristics, by profiling asthma (NCT01274507). This report presents for the first time the study design, and characteristics of the recruited subjects. Methods: Patients with a range of asthma severity and healthy non-atopic controls were enrolled. The asthmatic subjects were followed for 12 months. Assessments included history, patient questionnaires, spirometry, airway hyper-responsiveness to methacholine, fractional exhaled nitric oxide (FENO), and biomarkers measured in induced sputum, blood, and bronchoscopy samples. All subjects underwent sputum induction and 30 subjects/cohort had bronchoscopy. Results: Mild (n = 52), moderate (n = 55), severe (n = 51) asthma cohorts and 30 healthy controls were enrolled from North America and Western Europe. Airflow obstruction, bronchodilator response and airways hyperresponsiveness increased with asthma severity, and severe asthma subjects had reduced forced vital capacity. Asthma control questionnaire-7 (ACQ7) scores worsened with asthma severity. In the asthmatics, mean values for all clinical and biomarker characteristics were stable over 12 months although individual variability was evident. FENO and blood eosinophils did not differ by asthma severity. Induced sputum eosinophils but not neutrophils were lower in mild compared to the moderate and severe asthma cohorts. Conclusions: The ADEPT study successfully enrolled asthmatics across a spectrum of severity and non-atopic controls. Clinical characteristics were related to asthma severity and in general asthma characteristics e.g. lung function, were stable over 12 months. Use of the ADEPT data should prove useful in defining biological phenotypes to facilitate personalized therapeutic approaches. C1 [Silkoff, P. E.; Susulic, V. S.; Barnathan, E. S.; Curran, M.; Das, A. M.; Brodmerkel, C.; Baribaud, F.; Loza, M. J.] Janssen Res & Dev LLC, Spring House, PA 19477 USA. [Strambu, I.] Arensia Exploratory Med, Bucharest 050159, Romania. [Laviolette, M.] IUCPQ, Quebec City, PQ G1V 4G5, Canada. [Singh, D.] Univ Manchester, Univ Hosp South Manchester Fdn Trust, Med Evaluat Unit, Manchester M23 9QZ, Lancs, England. [FitzGerald, J. M.; Lam, S.] Inst Heart & Lung Hlth, Lung Ctr, Gordon, ON, Canada. [FitzGerald, J. M.; Lam, S.] Leslie Diamond Hlth Care Ctr, Vancouver, BC V5Z 1M9, Canada. [Kelsen, S.] Temple Univ, Dept Thorac Med & Surg, Sch Med, Philadelphia, PA 19140 USA. [Eich, A.] IKF Pneumol Frankfurt, Inst Klin Forsch Pneumol, Clin Res Ctr Resp Dis, D-360596 Frankfurt, Germany. [Ludwig-Sengpiel, A.] KLB Gesundheitsforsch Lubeck GmbH, D-23552 Lubeck, Germany. [Hupp, G. C.] Yale Univ, Sch Med, Div Pulm & Crit Care & Sleep Med, Yale Ctr Asthma & Airway Dis, New Haven, CT 06520 USA. [Backer, V.; Porsbjerg, C.] Bispebjerg Hosp, Resp Res Unit, Dept Resp Med, DK-2400 Copenhagen NV, Denmark. [Girodet, P. O.; Berger, P.] Univ Bordeaux, Ctr Rech Cardiothorac Bordeaux, INSERM, U1045, F-33000 Bordeaux, France. [Leigh, R.] Univ Calgary, Cumming Sch Med, Calgary, AB T2N 4Z6, Canada. [Kline, J. N.] Univ Iowa, Div Pulm Crit Care & Occupat Med, Iowa City, IA 52242 USA. [Dransfield, M.] Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA. [Dransfield, M.] Birmingham VA Med Ctr, Birmingham, AL 35294 USA. [Calhoun, W.] Univ Texas Med Branch, Galveston, TX 77555 USA. [Hussaini, A.] Parexel Int, Shelton Simmons MD, Brooklyn, MD 21225 USA. [Khatri, S.] Cleveland Clin, Dept Pulm & Crit Care, Cleveland, OH 44195 USA. [Chanez, P.] Aix Marseille Univ, Dept Resp Dis, Marseille, France. [Chanez, P.] Aix Marseille Univ, CNRS 7733, INSERM, UMR U1067,CIC Nord AP HM, Marseille, France. RP Silkoff, PE (reprint author), Janssen Res & Dev LLC, 1400 McKean Rd, Spring House, PA 19477 USA. EM psilkoff@its.jnj.com NR 42 TC 4 Z9 4 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-993X EI 1465-9921 J9 RESP RES JI Respir. Res. PD NOV 17 PY 2015 VL 16 AR 142 DI 10.1186/s12931-015-0299-y PG 15 WC Respiratory System SC Respiratory System GA CW1VS UT WOS:000364780500001 PM 26576744 ER PT J AU Choi, JK Zhu, AJ Jenkins, BG Hattori, S Kil, KE Takagi, T Ishii, S Miyakawa, T Brownell, AL AF Choi, Ji-Kyung Zhu, Aijun Jenkins, Bruce G. Hattori, Satoko Kil, Kun-Eek Takagi, Tsuyoshi Ishii, Shunsuke Miyakawa, Tsuyoshi Brownell, Anna-Liisa TI Combined behavioral studies and in vivo imaging of inflammatory response and expression of mGlu5 receptors in schnurri-2 knockout mice SO NEUROSCIENCE LETTERS LA English DT Article DE Schnurri-2 (Shn-2) knockout (KO) mice; PET; mGluR5; Inflammation; Schizophrenia ID BENZODIAZEPINE-RECEPTOR; PREPULSE INHIBITION; SCHIZOPHRENIA; PET; DEXTROAMPHETAMINE; NEUROINFLAMMATION; BRAIN; DRUG AB Schnurri-2 (Shn-2) knockout (KO) mice have been proposed as a preclinical neuroinflammatory schizophrenia model. We used behavioral studies and imaging markers that can be readily translated to human populations to explore brain effects of inflammation. Shn-2 KO mice and their littermate control mice were imaged with two novel PET ligands; an inflammation marker [C-11]PBR28 and the mGluR5 ligand [F-18]FPEB. Locomotor activity was measured using open field exploration with saline, methamphetamine or amphetamine challenge. A significantly increased accumulation of [C-11]PBR28 was found in the cortex, striatum, hippocampus and olfactory bulb of Shn-2 KO mice. Increased mGluR5 binding was also observed in the cortex and hippocampus of the Shn-2 KO mice. Open field locomotor testing revealed a large increase in novelty-induced hyperlocomotion in Shn-2 KO mice with abnormal (decreased) responses to either methamphetamine or amphetamine. These data provide additional support to demonstrate that the Shn-2 KO mouse model exhibits several behavioral and pathological markers resembling human schizophrenia making it an attractive translational model for the disease. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Choi, Ji-Kyung; Zhu, Aijun; Jenkins, Bruce G.; Kil, Kun-Eek; Brownell, Anna-Liisa] Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Choi, Ji-Kyung; Zhu, Aijun; Jenkins, Bruce G.; Kil, Kun-Eek; Brownell, Anna-Liisa] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Takagi, Tsuyoshi] RIKEN, Tsukuba Inst, Tsukuba, Ibaraki, Japan. [Takagi, Tsuyoshi] Aichi Human Serv Ctr, Inst Dev Res, Kasugai, Aichi, Japan. [Ishii, Shunsuke] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama, Japan. [Hattori, Satoko; Miyakawa, Tsuyoshi] Fujita Hlth Univ, Inst Comprehens Med Sci, Div Syst Med Sci, Toyoake, Aichi, Japan. [Miyakawa, Tsuyoshi] Natl Inst Physiol Sci, Sect Behav Patterns, Ctr Genet Anal Behav, Okazaki, Aichi 444, Japan. [Hattori, Satoko; Miyakawa, Tsuyoshi] Japan Sci & Technol Agcy, CREST, Kawaguchi, Saitama, Japan. RP Brownell, AL (reprint author), Martinos Ctr Biomed Imaging 149 2301, Charlestown, MA 02129 USA. EM abrownell@mgh.harvard.edu OI Miyakawa, Tsuyoshi/0000-0003-0137-8200 FU KAKENHI from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan [24111546, 25116526, 25242078]; CREST of Japan Science and Technology Agency; [NIMH-1R01MH091684-01]; [NIBIB-1R01EB012864]; [NCRR-1S10RR029495]; [NCRR-1S10RR02666] FX This study was supported by NIMH-1R01MH091684-01, NIBIB-1R01EB012864, NCRR-1S10RR029495 and NCRR-1S10RR02666 to ALB and by KAKENHI (24111546, 25116526, 25242078) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan and a grant from CREST of Japan Science and Technology Agency to TM. NR 27 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 EI 1872-7972 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV 16 PY 2015 VL 609 BP 159 EP 164 DI 10.1016/j.neulet.2015.10.037 PG 6 WC Neurosciences SC Neurosciences & Neurology GA CZ0CK UT WOS:000366772500028 PM 26483320 ER PT J AU Gao, CY Xie, R Yu, CY Ma, RS Dong, WJ Meng, H Zhang, Y Si, Y Zhang, Z Novakovic, V Zhang, Y Kou, JJ Bi, YY Li, BX Xie, RJ Gilbert, GE Zhou, J Shi, JL AF Gao, Chunyan Xie, Rui Yu, Chengyuan Ma, Ruishuang Dong, Weijun Meng, Huan Zhang, Yan Si, Yu Zhang, Zhuo Novakovic, Valerie Zhang, Yong Kou, Junjie Bi, Yayan Li, Baoxin Xie, Rujuan Gilbert, Gary E. Zhou, Jin Shi, Jialan TI Thrombotic Role of Blood and Endothelial Cells in Uremia through Phosphatidylserine Exposure and Microparticle Release SO PLOS ONE LA English DT Article ID CHRONIC KIDNEY-DISEASE; CHRONIC-RENAL-FAILURE; CIRCULATING MICROPARTICLES; RISK; APOPTOSIS; MEMBRANES; PROLIFERATION; EPIDEMIOLOGY; HEMODIALYSIS; COAGULATION AB The mechanisms contributing to an increased risk of thrombosis in uremia are complex and require clarification. There is scant morphological evidence of membrane-dependent binding of factor Xa (FXa) and factor Va (FVa) on endothelial cells (EC) in vitro. Our objectives were to confirm that exposed phosphatidylserine (PS) on microparticle (MP), EC, and peripheral blood cell (PBC) has a prothrombotic role in uremic patients and to provide visible and morphological evidence of PS-dependent prothrombinase assembly in vitro. We found that uremic patients had more circulating MP (derived from PBC and EC) than controls. Additionally, patients had more exposed PS on their MPs and PBCs, especially in the hemodialysis group. In vitro, EC exposed more PS in uremic toxins or serum. Moreover, reconstitution experiments showed that at the early stages, PS exposure was partially reversible. Using confocal microscopy, we observed that PS-rich membranes of EC and MP provided binding sites for FVa and FXa. Further, exposure of PS in uremia resulted in increased generation of FXa, thrombin, and fibrin and significantly shortened coagulation time. Lactadherin, a protein that blocks PS, reduced 80% of procoagulant activity on PBC, EC, and MP. Our results suggest that PBC and EC in uremic milieu are easily injured or activated, which exposes PS and causes a release of MP, providing abundant procoagulant membrane surfaces and thus facilitating thrombus formation. Blocking PS binding sites could become a new therapeutic target for preventing thrombosis. C1 [Gao, Chunyan; Shi, Jialan] Harbin Med Univ, Hosp 1, Dept Hematol, Harbin, Peoples R China. [Gao, Chunyan; Ma, Ruishuang; Zhang, Yan; Si, Yu; Zhang, Zhuo; Zhou, Jin] Harbin Med Univ Daqing, Dept Med Lab Sci & Technol, Daqing, Peoples R China. [Xie, Rui; Xie, Rujuan] Harbin Med Univ, Hosp 3, Dept Gastrointestinal Oncol, Harbin, Peoples R China. [Yu, Chengyuan] Harbin Med Univ, Hosp 1, Dept Nephrol, Harbin, Peoples R China. [Dong, Weijun] Harbin Med Univ, Hosp 5, Dept Gen Surg, Harbin, Peoples R China. [Meng, Huan; Kou, Junjie; Bi, Yayan] Harbin Med Univ, Hosp 2, Dept Cardiol, Harbin, Peoples R China. [Zhang, Yong; Li, Baoxin] Harbin Med Univ, Dept Pharmacol, Harbin, Peoples R China. [Novakovic, Valerie; Gilbert, Gary E.; Shi, Jialan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Med Dept,VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Xie, RJ (reprint author), Harbin Med Univ, Hosp 3, Dept Gastrointestinal Oncol, Harbin, Peoples R China. EM hydwkyuliang@yahoo.com.cn; jinzhouh85@163.com; jialan_shi@hms.harvard.edu FU National Natural Science Foundation of China [81470301, 81400097, 81270588]; National Natural Science Foundation of Heilongjiang Province [H2015109]; Heilongjiang Postdoctoral Science Foundation [LBH-Z13153]; China Postdoctoral Science Foundation [2014M550202]; Seed Fund of Harbin Medical University-Daqing [DQ2013-05] FX The study design, data collection, and analysis were supported by grants from the National Natural Science Foundation of China (81470301, 81400097, 81270588). The decision to publish and preparation of the manuscript were surpported by the National Natural Science Foundation of Heilongjiang Province (H2015109), Project Funded by Heilongjiang Postdoctoral Science Foundation (LBH-Z13153), Project Funded by China Postdoctoral Science Foundation (2014M550202), and Seed Fund of Harbin Medical University-Daqing (DQ2013-05). NR 36 TC 2 Z9 2 U1 2 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 16 PY 2015 VL 10 IS 11 AR e0142835 DI 10.1371/journal.pone.0142835 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW5XP UT WOS:000365070700081 PM 26580207 ER PT J AU Libert, T Grande, D Asch, DA AF Libert, Timothy Grande, David Asch, David A. TI What web browsing reveals about your health SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID INFORMATION AB Advertisers can learn a lot from our digital footprints, including about our health. Timothy Libert and colleagues argue that we need to tighten restrictions on such data for marketing purposes while looking at their potential to improve health C1 [Libert, Timothy] Univ Penn, Annenberg Sch Commun, Philadelphia, PA 19104 USA. [Grande, David; Asch, David A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Asch, David A.] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Asch, DA (reprint author), Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. EM asch@wharton.upenn.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BMJ-BRIT MED J JI BMJ-British Medical Journal PD NOV 16 PY 2015 VL 351 AR h5974 DI 10.1136/bmj.h5974 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA CW9XU UT WOS:000365352300004 PM 26572794 ER PT J AU Bainer, R Yui, Y Mumenthaler, S Mallick, P Liu, L Wu, HJ Podlaha, O Michor, F Liphardt, J Licht, J Weaver, V AF Bainer, Russell Yui, Yoshihiro Mumenthaler, Shannon Mallick, Parag Liu, Lin Wu, Hua-Jun Podlaha, Ondrej Michor, Franziska Liphardt, Jan Licht, Jonathan Weaver, Valerie TI Extracellular stiffness cues drive spatial reorganization of the genome to globally constrain RNA abundance SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Computational and Systems Biology of Cancer CY FEB 08-11, 2015 CL San Francisco, CA SP Amer Assoc Canc Res C1 [Bainer, Russell; Yui, Yoshihiro; Weaver, Valerie] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Mumenthaler, Shannon] Univ So Calif, Los Angeles, CA USA. [Mallick, Parag; Liphardt, Jan] Stanford Univ, Stanford, CA 94305 USA. [Liu, Lin; Wu, Hua-Jun; Podlaha, Ondrej; Michor, Franziska] Dana Farber Canc Inst, Boston, MA 02115 USA. [Licht, Jonathan] Northwestern Univ, Evanston, IL USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2015 VL 75 IS 22 SU 2 MA PR09 DI 10.1158/1538-7445.COMPSYSBIO-PR09 PG 1 WC Oncology SC Oncology GA DE9PU UT WOS:000370971000109 ER PT J AU Berger, AH Kim, E Brooks, A Ilic, N Shrestha, Y Tseng, YY Wu, XY Zou, LH Kamburov, A Yang, XP Zhu, C Keskula, P Seepo, S Hong, A Kantoff, P Ligon, KL Garraway, LA Doench, JG Root, DE Meyerson, M Hahn, WC Getz, G Golub, TR Boehm, JS AF Berger, Alice H. Kim, Eejung Brooks, Angela Ilic, Nina Shrestha, Yashaswi Tseng, Yuen-Yi Wu, Xiaoyun Zou, Lihua Kamburov, Atanas Yang, Xiaoping Zhu, Cong Keskula, Paula Seepo, Sara Hong, Andrew Kantoff, Philip Ligon, Keith L. Garraway, Levi A. Doench, John G. Root, David E. Meyerson, Matthew Hahn, William C. Getz, Gad Golub, Todd R. Boehm, Jesse S. TI Towards precision functional genomics via next-generation functional mapping of cancer variants SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Translation of the Cancer Genome CY FEB 07-09, 2015 CL San Francisco, CA SP Amer Assoc Canc Res C1 [Berger, Alice H.; Kim, Eejung; Brooks, Angela; Shrestha, Yashaswi; Tseng, Yuen-Yi; Wu, Xiaoyun; Zou, Lihua; Yang, Xiaoping; Zhu, Cong; Keskula, Paula; Seepo, Sara; Doench, John G.; Root, David E.; Golub, Todd R.; Boehm, Jesse S.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Ilic, Nina; Hong, Andrew; Kantoff, Philip; Ligon, Keith L.; Garraway, Levi A.; Meyerson, Matthew; Hahn, William C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kamburov, Atanas; Getz, Gad] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2015 VL 75 IS 22 SU 1 MA PR07 PG 2 WC Oncology SC Oncology GA DE9QJ UT WOS:000370972600121 ER PT J AU Brooks, AN Ge, YW Chau, K Freeman, SS Saksena, G Pedamallu, CS Meyerson, M AF Brooks, Angela N. Ge, Yawei Chau, Kevin Freeman, Samuel S. Saksena, Gordon Pedamallu, Chandra Sekhar Meyerson, Matthew TI Identification of somatic RNA splicing alterations in human cancers SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Computational and Systems Biology of Cancer CY FEB 08-11, 2015 CL San Francisco, CA SP Amer Assoc Canc Res C1 [Brooks, Angela N.; Freeman, Samuel S.; Saksena, Gordon; Pedamallu, Chandra Sekhar] Broad Inst, Cambridge, MA USA. [Ge, Yawei; Chau, Kevin] Harvard Univ, Sch Med, Boston, MA USA. [Meyerson, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2015 VL 75 IS 22 SU 2 MA B2-21 DI 10.1158/1538-7445.COMPSYSBIO-B2-21 PG 1 WC Oncology SC Oncology GA DE9PU UT WOS:000370971000066 ER PT J AU Broyde, J Simpson, D Wah, DA Giorgi, FM Petrey, D Alvarez, MJ Silkov, A Lachmann, A Hill, DE Vidal, M Jackson, P Honig, B Sweet-Cordero, A Califano, A AF Broyde, Joshua Simpson, David Wah, David A. Giorgi, Federico M. Petrey, Donald Alvarez, Mariano J. Silkov, Antonina Lachmann, Alexander Hill, David E. Vidal, Marc Jackson, Peter Honig, Barry Sweet-Cordero, Alejandro Califano, Andrea TI Systems and structural biology approaches to elucidate new effectors in KRAS mutant tumors SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Computational and Systems Biology of Cancer CY FEB 08-11, 2015 CL San Francisco, CA SP Amer Assoc Canc Res C1 [Broyde, Joshua; Wah, David A.; Giorgi, Federico M.; Petrey, Donald; Alvarez, Mariano J.; Silkov, Antonina; Lachmann, Alexander; Honig, Barry; Califano, Andrea] Columbia Univ, Irving Canc Res Ctr, Dept Syst Biol, New York, NY USA. [Simpson, David; Sweet-Cordero, Alejandro] Stanford Univ, Dept Pediat, Sch Med, Div Hematol Oncol, Stanford, CA 94305 USA. [Hill, David E.; Vidal, Marc] Dana Farber Canc Inst, CCSB, Boston, MA 02115 USA. [Hill, David E.; Vidal, Marc] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Jackson, Peter] Stanford Univ, Dept Microbiol & Immunol, Baxter Lab Stem Cell Biol, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2015 VL 75 IS 22 SU 2 MA PR13 DI 10.1158/1538-7445.COMPSYSBIO-PR13 PG 1 WC Oncology SC Oncology GA DE9PU UT WOS:000370971000112 ER PT J AU Gitlitz, BJ Morosini, D Sable-Hunt, A Addario, BJ Oxnard, GR AF Gitlitz, Barbara J. Morosini, Deborah Sable-Hunt, Alicia Addario, Bonnie J. Oxnard, Geoffrey R. TI The genomics of young lung cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Translation of the Cancer Genome CY FEB 07-09, 2015 CL San Francisco, CA SP Amer Assoc Canc Res C1 [Gitlitz, Barbara J.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Morosini, Deborah] Fdn Med Inc, Cambridge, MA USA. [Sable-Hunt, Alicia] Edwards Hunt Grp LLC, Plantation, FL USA. [Addario, Bonnie J.] Bonnie J Addario Lung Canc Fdn, San Carlos, CA USA. [Oxnard, Geoffrey R.] Dana Farber Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2015 VL 75 IS 22 SU 1 MA A1-36 DI 10.1158/1538-7445.TRANSCAGEN-A1-36 PG 2 WC Oncology SC Oncology GA DE9QJ UT WOS:000370972600032 ER PT J AU Hsieh, CL Botta, G Gao, S Li, TT Van Allen, EM Treacy, DJ Cai, CM He, HH Sweeney, CJ Brown, M Balk, SP Nelson, PS Garraway, LA Kantoff, PW AF Hsieh, Chen-Lin Botta, Ginevra Gao, Shuai Li, Tiantian Van Allen, Eliezer M. Treacy, Daniel J. Cai, Changmeng He, Housheng Hansen Sweeney, Christopher J. Brown, Myles Balk, Steven P. Nelson, Peter S. Garraway, Levi A. Kantoff, Philip W. TI PLZF, a tumor suppressor genetically lost in metastatic castration resistant prostate cancer, is a mediator of resistance to androgen deprivation therapy SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Translation of the Cancer Genome CY FEB 07-09, 2015 CL San Francisco, CA SP Amer Assoc Canc Res C1 [Hsieh, Chen-Lin; Botta, Ginevra; Li, Tiantian; Van Allen, Eliezer M.; Treacy, Daniel J.; Sweeney, Christopher J.; Brown, Myles; Garraway, Levi A.; Kantoff, Philip W.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gao, Shuai; Cai, Changmeng; Balk, Steven P.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [He, Housheng Hansen] Univ Toronto, Toronto, ON, Canada. [Nelson, Peter S.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2015 VL 75 IS 22 SU 1 MA A2-11 DI 10.1158/1538-7445.TRANSCAGEN-A2-11 PG 2 WC Oncology SC Oncology GA DE9QJ UT WOS:000370972600064 ER PT J AU Klco, JM Miller, CA Griffith, M Petti, A Spencer, DH Ketkar-Kulkarni, S Wartman, LD Christopher, M Lamprecht, TL Payton, JE Baty, J Heath, SE Griffith, OL Shen, D Hundal, J Chang, GS Fulton, RS O'laughlin, M Fronick, C Magrini, V Demeter, R Larson, DE Kulkarni, S Ozenberger, BA Welch, JS Walker, MJ Graubert, TA Westervelt, P Radich, JP Link, DC Mardis, ER DiPersio, JF Wilson, RK AF Klco, Jeffery M. Miller, Christopher A. Griffith, Malachi Petti, Allegra Spencer, David H. Ketkar-Kulkarni, Shamika Wartman, Lukas D. Christopher, Matthew Lamprecht, Tamara L. Payton, Jacqueline E. Baty, Jack Heath, Sharon E. Griffith, Obi L. Shen, Dong Hundal, Jasreet Chang, Gue Su Fulton, Robert S. O'laughlin, Michelle Fronick, Catrina Magrini, Vincent Demeter, Ryan Larson, David E. Kulkarni, Shashikant Ozenberger, Bradley A. Welch, John S. Walker, Matthew J. Graubert, Timothy A. Westervelt, Peter Radich, Jerald P. Link, Daniel C. Mardis, Elaine R. DiPersio, John F. Wilson, Richard K. TI Genomic approaches for risk assessment in acute myeloid leukemia SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Translation of the Cancer Genome CY FEB 07-09, 2015 CL San Francisco, CA SP Amer Assoc Canc Res ID MUTATIONS C1 [Klco, Jeffery M.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA. [Miller, Christopher A.; Griffith, Malachi; Petti, Allegra; Griffith, Obi L.; Hundal, Jasreet; Chang, Gue Su; Fulton, Robert S.; O'laughlin, Michelle; Fronick, Catrina; Magrini, Vincent; Demeter, Ryan; Larson, David E.; Ozenberger, Bradley A.; Mardis, Elaine R.; Wilson, Richard K.] Washington Univ, Genome Inst, St Louis, MO USA. [Spencer, David H.; Payton, Jacqueline E.; Kulkarni, Shashikant] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Ketkar-Kulkarni, Shamika; Wartman, Lukas D.; Christopher, Matthew; Heath, Sharon E.; Welch, John S.; Westervelt, Peter; Link, Daniel C.; DiPersio, John F.] Washington Univ, Sch Med, Dept Med, Div Oncol, St Louis, MO 63110 USA. [Lamprecht, Tamara L.] Washington Univ, Dept Pediat, Div Hematol Oncol, St Louis, MO 63130 USA. [Baty, Jack] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. [Shen, Dong] Medimmune AstraZeneca, Gaithersburg, MD USA. [Walker, Matthew J.; Radich, Jerald P.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Graubert, Timothy A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2015 VL 75 IS 22 SU 1 MA PR11 DI 10.1158/1538-7445.TRANSCAGEN-PR11 PG 2 WC Oncology SC Oncology GA DE9QJ UT WOS:000370972600124 ER PT J AU Klco, JM Miller, CA Griffith, M Petti, A Spencer, DH Ketkar-Kulkarni, S Wartman, LD Christopher, M Lamprecht, TL Payton, JE Baty, J Heath, SE Griffith, OL Shen, D Hundal, J Chang, GS Fulton, RS Olaughlin, M Fronick, C Magrini, V Demeter, R Larson, DE Kulkarni, S Ozenberger, BA Welch, JS Walker, MJ Graubert, TA Westervelt, P Radich, JP Link, DC Mardis, ER DiPersio, JF Wilson, RK AF Klco, Jeffery M. Miller, Christopher A. Griffith, Malachi Petti, Allegra Spencer, David H. Ketkar-Kulkarni, Shamika Wartman, Lukas D. Christopher, Matthew Lamprecht, Tamara L. Payton, Jacqueline E. Baty, Jack Heath, Sharon E. Griffith, Obi L. Shen, Dong Hundal, Jasreet Chang, Gue Su Fulton, Robert S. Olaughlin, Michelle Fronick, Catrina Magrini, Vincent Demeter, Ryan Larson, David E. Kulkarni, Shashikant Ozenberger, Bradley A. Welch, John S. Walker, Matthew J. Graubert, Timothy A. Westervelt, Peter Radich, Jerald P. Link, Daniel C. Mardis, Elaine R. DiPersio, John F. Wilson, Richard K. TI Genomic approaches for risk assessment in acute myeloid leukemia SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Computational and Systems Biology of Cancer CY FEB 08-11, 2015 CL San Francisco, CA SP Amer Assoc Canc Res ID MUTATIONS C1 [Klco, Jeffery M.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA. [Miller, Christopher A.; Griffith, Malachi; Petti, Allegra; Griffith, Obi L.; Hundal, Jasreet; Chang, Gue Su; Fulton, Robert S.; Olaughlin, Michelle; Fronick, Catrina; Magrini, Vincent; Demeter, Ryan; Larson, David E.; Ozenberger, Bradley A.; Mardis, Elaine R.; Wilson, Richard K.] Washington Univ, Genome Inst, St Louis, MO USA. [Spencer, David H.; Payton, Jacqueline E.; Kulkarni, Shashikant] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. [Ketkar-Kulkarni, Shamika; Wartman, Lukas D.; Christopher, Matthew; Heath, Sharon E.; Welch, John S.; Westervelt, Peter; Link, Daniel C.; DiPersio, John F.] Washington Univ, Sch Med, Dept Med, Div Oncol, St Louis, MO 63110 USA. [Lamprecht, Tamara L.] Washington Univ, Dept Pediat, Div Hematol Oncol, St Louis, MO 63130 USA. [Baty, Jack] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. [Shen, Dong] Medimmune AstraZeneca, Gaithersburg, MD USA. [Walker, Matthew J.; Radich, Jerald P.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Graubert, Timothy A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2015 VL 75 IS 22 SU 2 MA PR03 DI 10.1158/1538-7445.COMPSYSBIO-PR03 PG 2 WC Oncology SC Oncology GA DE9PU UT WOS:000370971000103 ER PT J AU Kuijjer, ML Glass, K Quackenbush, J AF Kuijjer, Marieke Lydia Glass, Kimberly Quackenbush, John TI Gene regulation by transcription factors and microRNAs in ovarian cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Computational and Systems Biology of Cancer CY FEB 08-11, 2015 CL San Francisco, CA SP Amer Assoc Canc Res C1 [Kuijjer, Marieke Lydia; Quackenbush, John] Dana Farber Canc Inst, Boston, MA 02115 USA. [Glass, Kimberly] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2015 VL 75 IS 22 SU 2 MA B1-20 DI 10.1158/1538-7445.COMPSYSBIO-B1-20 PG 1 WC Oncology SC Oncology GA DE9PU UT WOS:000370971000018 ER PT J AU Nickerson, ML Im, KM Turan, S Guo, GW Moore, LE Theodorescu, D Dean, M AF Nickerson, Michael L. Im, Kate M. Turan, Sevilay Guo, Guangwu Moore, Lee E. Theodorescu, Dan Dean, Michael TI Translational genomics of urologic cancer genes SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Translation of the Cancer Genome CY FEB 07-09, 2015 CL San Francisco, CA SP Amer Assoc Canc Res C1 [Nickerson, Michael L.; Turan, Sevilay; Dean, Michael] NCI, Frederick, MD 21701 USA. [Im, Kate M.] Data Sci Genom, Ellicott City, MD USA. [Guo, Guangwu] Dana Farber Canc Inst, Boston, MA 02115 USA. [Moore, Lee E.] NCI, Rockville, MD USA. [Theodorescu, Dan] Univ Colorado, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2015 VL 75 IS 22 SU 1 MA A1-01 DI 10.1158/1538-7445.TRANSCAGEN-A1-01 PG 2 WC Oncology SC Oncology GA DE9QJ UT WOS:000370972600003 ER PT J AU Place, CS Kim, IK Esmaeli, B Amin-Mansour, A Treacy, DJ Carter, SL Hodis, E Wagle, N Seepo, S Yu, XX Vazquez, F Nickerson, E Cibulskis, K McKenna, A Gabriel, SB Getz, G Van Allen, EM Garraway, LA Woodman, SE AF Place, Chelsea S. Kim, Ivana K. Esmaeli, Bita Amin-Mansour, Ali Treacy, Daniel J. Carter, Scott L. Hodis, Eran Wagle, Nikhil Seepo, Sara Yu, Xiaoxing Vazquez, Francisca Nickerson, Elizabeth Cibulskis, Kristian McKenna, Aaron Gabriel, Stacey B. Getz, Gad Van Allen, Eliezer M. Garraway, Levi A. Woodman, Scott E. TI Systematic genomic characterization of uveal melanoma SO CANCER RESEARCH LA English DT Meeting Abstract CT AACR Special Conference on Translation of the Cancer Genome CY FEB 07-09, 2015 CL San Francisco, CA SP Amer Assoc Canc Res C1 [Place, Chelsea S.; Treacy, Daniel J.; Wagle, Nikhil; Van Allen, Eliezer M.; Garraway, Levi A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kim, Ivana K.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Esmaeli, Bita; Yu, Xiaoxing; Woodman, Scott E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Amin-Mansour, Ali; Carter, Scott L.; Hodis, Eran; Seepo, Sara; Vazquez, Francisca; Nickerson, Elizabeth; Cibulskis, Kristian; McKenna, Aaron; Gabriel, Stacey B.; Getz, Gad] Broad Inst Harvard & MIT, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2015 VL 75 IS 22 SU 1 MA A1-15 DI 10.1158/1538-7445.TRANSCAGEN-A1-15 PG 2 WC Oncology SC Oncology GA DE9QJ UT WOS:000370972600015 ER PT J AU Ciaranello, AL Matthews, LT AF Ciaranello, Andrea L. Matthews, Lynn T. TI Safer Conception Strategies for HIV-Serodiscordant Couples: How Safe Is Safe Enough? SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; EXPOSED UNINFECTED INFANTS; RANDOMIZED CLINICAL-TRIAL; PREEXPOSURE PROPHYLAXIS; ANTIRETROVIRAL THERAPY; AFRICAN WOMEN; RURAL UGANDA; INFECTION; PREVENTION; PREGNANCY C1 [Ciaranello, Andrea L.; Matthews, Lynn T.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Ciaranello, Andrea L.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Matthews, Lynn T.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. RP Ciaranello, AL (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 50 Staniford St,Rm 936, Boston, MA 02114 USA. EM aciaranello@partners.org FU NICHD NIH HHS [R01 HD079214, R01HD079214]; NIMH NIH HHS [K23 MH095655] NR 42 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 15 PY 2015 VL 212 IS 10 BP 1525 EP 1528 DI 10.1093/infdis/jiv275 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA DB7BE UT WOS:000368668600001 PM 26092857 ER PT J AU Delgado, RN Lim, DA AF Delgado, Ryan N. Lim, Daniel A. TI Embryonic Nkx2.1-expressing neural precursor cells contribute to the regional heterogeneity of adult V-SVZ neural stem cells SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Stem cell heterogeneity; Neural stem cells; Adult neurogenesis; V-SVZ; Positional identity; Regional patterning; Nkx2.1 ID OLFACTORY-BULB; MAMMALIAN BRAIN; SUBVENTRICULAR ZONE; NEURONAL MIGRATION; TELENCEPHALON; INTERNEURONS; ORGANIZATION; DIVERSITY; GRANULE; ORIGIN AB The adult ventricular-subventricular zone (V-SVZ) of the lateral ventricle produces several subtypes of olfactory bulb (OB) interneurons throughout life. Neural stem cells (NSCs) within this zone are heterogeneous, with NSCs located in different regions of the lateral ventricle wall generating distinct OB interneuron subtypes. The regional expression of specific transcription factors appears to correspond to such geographical differences in the developmental potential of V-SVZ NSCs. However, the transcriptional definition and developmental origin of V-SVZ NSC regional identity are not well understood. In this study, we found that a population of NSCs in the ventral region of the V-SVZ expresses the transcription factor Nkx2.1 and is derived from Nkx2.1-expressing (Nkx2.1 +) embryonic precursors. To follow the fate of Nkx2.1 + cells and their progeny in vivo, we used mice with an Nkx2.1-CreER "knock-in" allele. Nkx2.1 + V-SVZ NSCs labeled in adult mice generated interneurons for the deep granule cell layer of the OB. Embryonic brain Nkx2.1 + precursors labeled at embryonic day 12.5 gave rise to Nkx2.1 + NSCs of the ventral V-SVZ in postnatal and adult mice. Thus, embryonic Nkx2.1 + neural precursors give rise to a population of Nkx2.1 + NSCs in the ventral V-SVZ where they contribute to the regional heterogeneity of V-SVZ NSCs. Published by Elsevier Inc. C1 [Delgado, Ryan N.; Lim, Daniel A.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Delgado, Ryan N.; Lim, Daniel A.] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA. [Delgado, Ryan N.] Univ Calif San Francisco, Program Biomed Sci, San Francisco, CA 94143 USA. [Delgado, Ryan N.] Univ Calif San Francisco, Med Scientist Training Program, San Francisco, CA 94143 USA. [Lim, Daniel A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. RP Lim, DA (reprint author), Univ Calif San Francisco, Dept Neurol Surg, 35 Med Ctr Way, San Francisco, CA 94143 USA. EM Daniel.Lim@ucsf.edu FU NIH [DP2-OD006505-01]; VA [2101 BX000252-04]; CIRM Predoctoral Fellowship [TG2-01153]; MSTP training grant [2T32GM007618-34] FX We thank L. Fuentealba and A. Alvarez-Buylla for helpful comments and suggestions, R. Andersen for careful review of the manuscript, and M. Bedolli for assisting in the caesarean delivery of tamoxifen-treated embryos. This work was funded by: NIH DP2-OD006505-01, VA 2101 BX000252-04, CIRM Predoctoral Fellowship (TG2-01153), MSTP training grant 2T32GM007618-34.. NR 45 TC 2 Z9 3 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 EI 1095-564X J9 DEV BIOL JI Dev. Biol. PD NOV 15 PY 2015 VL 407 IS 2 BP 265 EP 274 DI 10.1016/j.ydbio.2015.09.008 PG 10 WC Developmental Biology SC Developmental Biology GA CY0AK UT WOS:000366068100008 PM 26387477 ER PT J AU Lavine, JA Kibbe, CR Baan, M Sirinvaravong, S Umhoefer, HM Engler, KA Meske, LM Sacotte, KA Erhardt, DP Davis, DB AF Lavine, Jeremy A. Kibbe, Carly R. Baan, Mieke Sirinvaravong, Sirinart Umhoefer, Heidi M. Engler, Kimberly A. Meske, Louise M. Sacotte, Kaitlyn A. Erhardt, Daniel P. Davis, Dawn Belt TI Cholecystokinin expression in the beta-cell leads to increased beta-cell area in aged mice and protects from streptozotocin-induced diabetes and apoptosis SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE cholecystokinin; islet; beta-cell; apoptosis; aging; streptozotocin ID FAT-FED MICE; INSULIN-SECRETION; GENE-EXPRESSION; MOUSE MODELS; ALPHA-CELLS; IN-VIVO; RECEPTOR; PANCREAS; ISLETS; LOCALIZATION AB Cholecystokinin (CCK) is a peptide hormone produced in the gut and brain with beneficial effects on digestion, satiety, and insulin secretion. CCK is also expressed in pancreatic beta-cells, but only in models of obesity and insulin resistance. Whole body deletion of CCK in obese mice leads to reduced beta-cell mass expansion and increased apoptosis. We hypothesized that islet-derived CCK is important in protection from beta-cell apoptosis. To determine the specific role of beta-cell-derived CCK in beta-cell mass dynamics, we generated a transgenic mouse that expresses CCK in the beta-cell in the lean state (MIP-CCK). Although this transgene contains the human growth hormone minigene, we saw no expression of human growth hormone protein in transgenic islets. We examined the ability of MIP-CCK mice to maintain beta-cell mass when subjected to apoptotic stress, with advanced age, and after streptozotocin treatment. Aged MIP-CCK mice have increased beta-cell area. MIP-CCK mice are resistant to streptozotocin- induced diabetes and exhibit reduced beta-cell apoptosis. Directed CCK overexpression in cultured beta-cells also protects from cytokine-induced apoptosis. We have identified an important new paracrine/autocrine effect of CCK in protection of beta-cells from apoptotic stress. Understanding the role of beta-cell CCK adds to the emerging knowledge of classic gut peptides in intraislet signaling. CCK receptor agonists are being investigated as therapeutics for obesity and diabetes. While these agonists clearly have beneficial effects on body weight and insulin sensitivity in peripheral tissues, they may also directly protect beta-cells from apoptosis. C1 [Lavine, Jeremy A.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Kibbe, Carly R.; Baan, Mieke; Sirinvaravong, Sirinart; Umhoefer, Heidi M.; Engler, Kimberly A.; Meske, Louise M.; Sacotte, Kaitlyn A.; Erhardt, Daniel P.; Davis, Dawn Belt] Univ Wisconsin, Dept Med, Div Endocrinol, Madison, WI USA. [Davis, Dawn Belt] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ Ctr, Madison, WI USA. [Davis, Dawn Belt] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Clin Ctr, Madison, WI USA. RP Davis, DB (reprint author), 4147 MFCB,1685 Highland Ave, Madison, WI 53705 USA. EM dbd@medicine.wisc.edu FU Medical Scientist Training Program [T32 GM-08692]; National Institute on Aging [5T32 AG-000213]; National Institutes of Health [T32 RR-023916, T32 OD-010423]; National Institute of Diabetes and Digestive and Kidney Diseases [DK-083442]; US Department of Veterans Affairs [1I01BX001880]; University of Wisconsin; Wisconsin Partnership Program FX J. A. Lavine was supported by the Medical Scientist Training Program (T32 GM-08692). C. R. Kibbe is funded by National Institute on Aging (5T32 AG-000213). M. Baan was supported by the National Institutes of Health training grants T32 RR-023916 and T32 OD-010423. D. B. Davis has received funding from the National Institute of Diabetes and Digestive and Kidney Diseases (DK-083442), US Department of Veterans Affairs (1I01BX001880), the University of Wisconsin, and the Wisconsin Partnership Program. NR 51 TC 2 Z9 2 U1 1 U2 4 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 NOV 15 PY 2015 VL 309 IS 10 BP E819 EP E828 DI 10.1152/ajpendo.00159.2015 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA CX7JP UT WOS:000365878300001 PM 26394663 ER PT J AU Vu, JP Goyal, D Luong, L Oh, S Sandhu, R Norris, J Parsons, W Pisegna, JR Germano, PM AF Vu, John P. Goyal, Deepinder Luong, Leon Oh, Suwan Sandhu, Ravneet Norris, Joshua Parsons, William Pisegna, Joseph R. Germano, Patrizia M. TI PACAP intraperitoneal treatment suppresses appetite and food intake via PAC1 receptor in mice by inhibiting ghrelin and increasing GLP-1 and leptin SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE pituitary adenylate cyclase-activating peptide; PAC1 receptor; appetite; ghrelin; GLP-1; leptin ID CYCLASE-ACTIVATING POLYPEPTIDE; VASOACTIVE-INTESTINAL-PEPTIDE; STIMULATES ADENYLATE-CYCLASE; GASTRIC-ACID-SECRETION; IN-SITU HYBRIDIZATION; PARAVENTRICULAR NUCLEUS; INSULIN SENSITIVITY; TISSUE DISTRIBUTION; GLUCOSE-TOLERANCE; MOLECULAR-CLONING AB Pituitary adenylate cyclase-activating peptide (PACAP) is expressed within the gastroenteric system, where it has profound physiological effects. PACAP was shown to regulate food intake and thermogenesis centrally; however, PACAP peripheral regulation of appetite and feeding behavior is unknown. Therefore, we studied PACAP's effect on appetite and food intake control by analyzing feeding behavior and metabolic hormones in PAC1-deficient (PAC1-/-) and age-matched wild-type (WT) mice intraperitoneally injected with PACAP(1-38) or PACAP(1-27) before the dark phase of feeding. Food intake and feeding behavior were analyzed using the BioDAQ system. Active ghrelin, glucagon-like peptide-1 (GLP-1), leptin, peptide YY, pancreatic polypeptide, and insulin were measured following PACAP(1-38) administration in fasted WT mice. PACAP(1-38)/PACAP(1-27) injected into WT mice significantly decreased in a dose-dependent manner cumulative food intake and reduced bout and meal feeding parameters. Conversely, PACAP(1-38) injected into PAC1-/- mice failed to significantly change food intake. Importantly, PACAP(1-38) reduced plasma levels of active ghrelin compared with vehicle in WT mice. In PAC1-/- mice, fasting levels of active ghrelin, GLP-1, insulin, and leptin and postprandial levels of active ghrelin and insulin were significantly altered compared with levels in WT mice. Therefore, PAC1 is a novel regulator of appetite/satiety. PACAP(1-38)/PACAP(1-27) significantly reduced appetite and food intake through PAC1. In PAC1-/- mice, the regulation of anorexigenic/orexigenic hormones was abolished, whereas active ghrelin remained elevated even postprandially. PACAP significantly reduced active ghrelin in fasting conditions. These results establish a role for PACAP via PAC1 in the peripheral regulation of appetite/satiety and suggest future studies to explore a therapeutic use of PACAP or PAC1 agonists for obesity treatment. C1 [Vu, John P.; Oh, Suwan; Sandhu, Ravneet; Norris, Joshua; Parsons, William; Pisegna, Joseph R.; Germano, Patrizia M.] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. [Goyal, Deepinder] Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA. [Luong, Leon; Parsons, William; Pisegna, Joseph R.] Univ Calif Los Angeles, Mol Cellular & Integrat Physiol Program, Los Angeles, CA USA. [Pisegna, Joseph R.] Vet Affairs Greater Angeles Healthcare Syst, Div Gastroenterol Hepatol & Parenteral Nutr, Los Angeles, CA USA. [Pisegna, Joseph R.; Germano, Patrizia M.] Univ Calif Los Angeles, Dept Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90024 USA. [Germano, Patrizia M.] Vet Affairs Greater Angeles Healthcare Syst, Div Pulm & Crit Care, Los Angeles, CA USA. RP Germano, PM (reprint author), Univ Calif Los Angeles, Dept Vet Affairs, CURE, Greater Los Angeles Med Ctr, Bldg 115,Rm 313, Los Angeles, CA USA. EM pgermano@ucla.edu FU two Department of Veterans Affairs Merit Review Awards; Department of Veterans Affairs Merit Review Shared Equipment Evaluation Program; National Institute of Diabetes and Digestive and Kidney Diseases [P30 DK-41301] FX This work was supported by two Department of Veterans Affairs Merit Review Awards (to P. Germano and J. R. Pisegna), the Department of Veterans Affairs Merit Review Shared Equipment Evaluation Program (to P. Germano), and National Institute of Diabetes and Digestive and Kidney Diseases Grant P30 DK-41301 (to CURE: Digestive Diseases Research Center, Models of Gastrointestinal Function and Disease Core). NR 62 TC 2 Z9 2 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 EI 1522-1547 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD NOV 15 PY 2015 VL 309 IS 10 BP G816 EP G825 DI 10.1152/ajpgi.00190.2015 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA CX7JL UT WOS:000365877900004 PM 26336928 ER PT J AU Wells, JM Gaggar, A Nicod, LP AF Wells, J. Michael Gaggar, Amit Nicod, Laurent P. TI A Fragment in Time Elastin Peptides and Progression of Emphysema SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID OBSTRUCTIVE PULMONARY-DISEASE; SMOKERS; COPD; CT C1 [Wells, J. Michael; Gaggar, Amit] Univ Alabama Birmingham, Div Pulm Allergy & Crit Care, Birmingham, AL 35233 USA. [Wells, J. Michael; Gaggar, Amit] Univ Alabama Birmingham, Lung Hlth Ctr, Birmingham, AL USA. [Wells, J. Michael; Gaggar, Amit] Birmingham VA Med Ctr, Birmingham, AL USA. [Nicod, Laurent P.] Univ Lausanne Hosp, Serv Pneumol, Lausanne, Switzerland. RP Wells, JM (reprint author), Univ Alabama Birmingham, Div Pulm Allergy & Crit Care, Birmingham, AL 35233 USA. FU NHLBI NIH HHS [K08 HL123940] NR 15 TC 1 Z9 1 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 15 PY 2015 VL 192 IS 10 BP 1141 EP 1143 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CW6XY UT WOS:000365142900001 PM 26568233 ER PT J AU Palevsky, PM AF Palevsky, Paul M. TI High-Volume Hemofiltration in Post-Cardiac Surgery Shock A Heroic Therapy? SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID ACUTE KIDNEY INJURY; RENAL REPLACEMENT THERAPY; RANDOMIZED CONTROLLED-TRIAL; INITIATION; STANDARD; METAANALYSIS; BYPASS C1 [Palevsky, Paul M.] VA Pittsburgh Healthcare Syst, Med Serv, Pittsburgh, PA 15240 USA. [Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Med Serv, Pittsburgh, PA 15240 USA. OI Palevsky, Paul/0000-0002-7334-5400 NR 14 TC 0 Z9 0 U1 2 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 15 PY 2015 VL 192 IS 10 BP 1143 EP 1144 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CW6XY UT WOS:000365142900002 PM 26568234 ER PT J AU Tanner, NT Silvestri, GA AF Tanner, Nichole T. Silvestri, Gerard A. TI What's in a Number? When It Comes to Pulmonary Nodules, It's All About the Number SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID LUNG-CANCER; DIAGNOSTIC EVALUATION; MANAGEMENT; PHYSICIANS; VOLUME C1 [Tanner, Nichole T.] Ralph H Johnson Vet Affairs Hosp, HEROIC, Charleston, SC 29401 USA. [Tanner, Nichole T.; Silvestri, Gerard A.] Med Univ S Carolina, Div Pulm & Crit Care Med, Charleston, SC 29425 USA. RP Tanner, NT (reprint author), Ralph H Johnson Vet Affairs Hosp, HEROIC, Charleston, SC 29401 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 15 PY 2015 VL 192 IS 10 BP 1149 EP 1150 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CW6XY UT WOS:000365142900005 PM 26568237 ER PT J AU Amalakuhan, B Maselli, DJ Martinez-Garcia, MA AF Amalakuhan, Bravein Maselli, Diego J. Martinez-Garcia, Miguel A. TI Update in Bronchiectasis 2014 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID CYSTIC FIBROSIS BRONCHIECTASIS; RANDOMIZED CONTROLLED-TRIAL; AIRWAY EPITHELIAL-CELLS; OF-LIFE QUESTIONNAIRE; LUNG CLEARANCE INDEX; RHEUMATOID-ARTHRITIS; EXACERBATIONS; MACROLIDES; CHILDREN; METAANALYSIS C1 [Amalakuhan, Bravein; Maselli, Diego J.] Univ Texas Hlth Sci Ctr San Antonio, Div Pulm Dis Crit Care Med, Dept Med, San Antonio, TX 78229 USA. [Amalakuhan, Bravein; Maselli, Diego J.] South Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. [Martinez-Garcia, Miguel A.] Univ & Polytech La Fe Hosp, Pneumol Serv, Valencia, Spain. RP Amalakuhan, B (reprint author), South Texas Vet Hlth Care Syst, Audie L Murphy Mem Vet Hosp, Pulm Dis Sect, 5th Floor,7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM amalakuhan@uthscsa.edu NR 49 TC 3 Z9 3 U1 1 U2 8 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 15 PY 2015 VL 192 IS 10 BP 1155 EP 1161 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CW6XY UT WOS:000365142900008 PM 26568240 ER PT J AU Bhavani, S Tsai, CL Perusich, S Hesselbacher, S Coxson, H Pandit, L Corry, DB Kheradmand, F AF Bhavani, Sivasubramanium Tsai, Chu-Lin Perusich, Sarah Hesselbacher, Sean Coxson, Harvey Pandit, Lavannya Corry, David B. Kheradmand, Farrah TI Clinical and Immunological Factors in Emphysema Progression Five-Year Prospective Longitudinal Exacerbation Study of Chronic Obstructive Pulmonary Disease (LES-COPD) SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE emphysema progression; T cells; IFN-gamma; IL-6; IL-17 ID LUNG-CANCER; REFERENCE VALUES; FUNCTION TESTS; SMOKING; MORTALITY; ECLIPSE; POPULATION; DECLINE; SMOKERS; VOLUME AB Rationale: Cross-sectional studies of T-cell responses to self-antigens correlate with baseline emphysema severity. Objectives: We investigated whether clinical and/or immunological factors could predict disease progression, such as emphysema, FEVI, and 6-minute-walk distance (6MWD), in former and active smokers in a 5-year prospective study. Methods: We recruited 224 ever smokers over 40 years of age and with greater than a 15 pack-year smoking history. Measurements and Main Results: Repeated spirometry, 6MWD, and peripheral blood T-cell cytokine responses to lung elastin fragments were measured. Baseline and repeat chest computed tomography (CT) scans (34 to 65 mo apart) were used to quantify emphysema progression. Of the 141 ever-smokers with baseline and repeat CT scans, the mean (SD) annual rate of change in percent emphysema was +0.46 (0.92), ranging from -1.8 to +4.1. In multivariable analyses, the rate of emphysema progression was greater in subjects who had lower body mass index (BMI) (+0.15 per 5-unit decrease in BMI; 95% confidence interval, +0.03 to +0.29). In active smokers, increased IFN-gamma and IL-6 T-cell responses had a positive association with the annual rate of emphysema progression. Male sex and IL-6 T-cell responses to elastin fragments were significantly associated with annual 6MWD decline, whereas IL-13 was associated with an increase in annual 6MWD. Conclusions: The rate of emphysema progression quantified by CT scans among ever-smokers was highly variable; clinical factors and biomarkers explained only some of the variability. Aggressive clinical care that targets active smokers with autoreactive T cells and low BMI may temporize progression of emphysema. C1 [Bhavani, Sivasubramanium; Perusich, Sarah; Hesselbacher, Sean; Pandit, Lavannya; Corry, David B.; Kheradmand, Farrah] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Corry, David B.; Kheradmand, Farrah] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Corry, David B.; Kheradmand, Farrah] Baylor Coll Med, Biol Inflammat Ctr, Houston, TX 77030 USA. [Tsai, Chu-Lin] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Tsai, Chu-Lin] Natl Taiwan Univ Hosp, Dept Emergency Med, Taipei, Taiwan. [Coxson, Harvey] Univ British Columbia, Vancouver Gen Hosp, Dept Radiol, Vancouver, BC V5Z 1M9, Canada. [Pandit, Lavannya; Corry, David B.; Kheradmand, Farrah] Michael E DeBakey Vet Affairs Ctr Translat Res In, Houston, TX USA. RP Kheradmand, F (reprint author), Baylor Coll Med, One Baylor Plaza,Suite 520B, Houston, TX 77030 USA. EM farrahk@bcm.edu RI Coxson, Harvey/A-9861-2017; OI Coxson, Harvey/0000-0001-5750-9711; Kheradmand, Farrah/0000-0001-5343-103X; TSAI, CHU-LIN/0000-0003-4639-1513 FU National Institutes of Health [HL082487, HL110883]; Veterans Affairs merit award; Baylor College of Medicine Cardiovascular Research Institute Pilot Project Award FX Supported by the National Institutes of Health grants HL082487 and HL110883 (F.K. and D.B.C.), a Veterans Affairs merit award, and Baylor College of Medicine Cardiovascular Research Institute Pilot Project Award (F.K.). NR 34 TC 8 Z9 8 U1 1 U2 4 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 15 PY 2015 VL 192 IS 10 BP 1171 EP 1178 DI 10.1164/rccm.201504-0736OC PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CW6XY UT WOS:000365142900010 PM 26241705 ER PT J AU Zazzeron, L Liu, C Franco, W Nakagawa, A Farinelli, WA Bloch, DB Anderson, RR Zapol, WM AF Zazzeron, Luca Liu, Chen Franco, Walfre Nakagawa, Akito Farinelli, William A. Bloch, Donald B. Anderson, R. Rox Zapol, Warren M. TI Pulmonary Phototherapy for Treating Carbon Monoxide Poisoning SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE carbon monoxide; poisoning; carboxyhemoglobin; phototherapy ID HYPERBARIC-OXYGEN; RAT-BRAIN; HELICOBACTER-PYLORI; CLINICAL-TRIAL; CARBOXYHEMOGLOBIN; INTOXICATION; ELIMINATION; THERAPY; HYPOXIA; OXIDASE AB Rationale: Carbon monoxide (CO) exposure is a leading cause of poison-related mortality. CO binds to Hb, forming carboxyhemoglobin (COHb), and produces tissue damage. Treatment of CO poisoning requires rapid removal of CO and restoration of oxygen delivery. Visible light is known to effectively dissociate CO from Hb, with a single photon dissociating one CO molecule. Objectives: To determine whether illumination of the lungs of CO-poisoned mice causes dissociation of COHb from blood transiting the lungs, releasing CO into alveoli and thereby enhancing the rate of CO elimination. Methods: We developed a model of CO poisoning in anesthetized and mechanically ventilated mice to assess the effects of direct lung illumination (phototherapy) on the CO elimination rate. Light at wavelengths between 532 and 690 nm was tested. The effect of lung phototherapy administered during CO poisoning was also studied. To avoid a thoracotomy, we assessed the effect of lung phototherapy delivered to murine lungs via an optical fiber placed in the esophagus. Measurements and Main Results: In CO-poisoned mice, phototherapy of exposed lungs at 532, 570, 592, and 628 nm dissociated CO from Hb and doubled the CO elimination rate. Phototherapy administered during severe CO poisoning limited the blood COHb increase and improved the survival rate. Noninvasive transesophageal phototherapy delivered to murine lungs via an optical fiber increased the rate of CO elimination while avoiding a thoracotomy. Conclusions: Future development and scaling up of lung phototherapy for patients with CO exposure may provide a significant advance for treating and preventing CO poisoning. C1 [Zazzeron, Luca; Liu, Chen; Nakagawa, Akito; Bloch, Donald B.; Zapol, Warren M.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA. [Franco, Walfre; Farinelli, William A.; Anderson, R. Rox] Massachusetts Gen Hosp, Wellman Ctr Photomed, Dept Dermatol, Boston, MA 02114 USA. [Bloch, Donald B.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Zapol, WM (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res, 55 Fruit St, Boston, MA 02114 USA. EM wzapol@mgh.harvard.edu FU Leducq Fondation; National Institutes of Health [R01DK082971] FX Supported by the Leducq Fondation and National Institutes of Health grant R01DK082971 (D.B.B.). NR 40 TC 3 Z9 3 U1 2 U2 5 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 15 PY 2015 VL 192 IS 10 BP 1191 EP 1199 DI 10.1164/rccm.201503-0609OC PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA CW6XY UT WOS:000365142900012 PM 26214119 ER PT J AU Deshmukh, AA Chhatwal, J Chiao, EY Nyitray, AG Das, P Cantor, SB AF Deshmukh, Ashish A. Chhatwal, Jagpreet Chiao, Elizabeth Y. Nyitray, Alan G. Das, Prajnan Cantor, Scott B. TI Long-Term Outcomes of Adding HPV Vaccine to the Anal Intraepithelial Neoplasia Treatment Regimen in HIV-Positive Men Who Have Sex With Men SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE human papillomavirus; quadrivalent human papillomavirus vaccine; secondary/adjunct prevention; anal neoplasia; cost-effectiveness analysis ID HUMAN-PAPILLOMAVIRUS VACCINATION; MULTICENTER AIDS COHORT; ANTIRETROVIRAL THERAPY; COST-EFFECTIVENESS; INFECTED PATIENTS; UNITED-STATES; RISK GROUPS; CANCER; PREVENTION; LESIONS AB Background. Recent evidence shows that quadrivalent human papillomavirus (qHPV) vaccination in men who have sex with men (MSM) who have a history of high-grade anal intraepithelial neoplasia (HGAIN) was associated with a 50% reduction in the risk of recurrent HGAIN. We evaluated the long-term clinical and economic outcomes of adding the qHPV vaccine to the treatment regimen for HGAIN in human immunodeficiency virus (HIV)-positive MSM aged >= 27 years. Methods. We constructed a Markov model based on anal histology in HIV-positive MSM comparing qHPV vaccination with no vaccination after treatment for HGAIN, the current practice. The model parameters, including baseline prevalence, disease transitions, costs, and utilities, were either obtained from the literature or calibrated using a natural history model of anal carcinogenesis. The model outputs included lifetime costs, quality-adjusted life years, and lifetime risk of developing anal cancer. We estimated the incremental cost-effectiveness ratio of qHPV vaccination compared to no qHPV vaccination and decrease in lifetime risk of anal cancer. We also conducted deterministic and probabilistic sensitivity analyses to evaluate the robustness of the results. Results. Use of qHPV vaccination after treatment for HGAIN decreased the lifetime risk of anal cancer by 63% compared with no vaccination. The qHPV vaccination strategy was cost saving; it decreased lifetime costs by $419 and increased quality-adjusted life years by 0.16. Results were robust to the sensitivity analysis. Conclusions. Vaccinating HIV-positive MSM aged >= 27 years with qHPV vaccine after treatment for HGAIN is a cost-saving strategy. Therefore, expansion of current vaccination guidelines to include this population should be a high priority. C1 [Deshmukh, Ashish A.; Cantor, Scott B.] Univ Texas MD Anderson Canc Ctr, Dept Hlth Serv Res, Houston, TX 77230 USA. [Deshmukh, Ashish A.] Univ Texas MD Anderson Canc Ctr, Canc Prevent Training Res Program, Houston, TX 77230 USA. [Das, Prajnan] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77230 USA. [Nyitray, Alan G.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Div Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA. [Chiao, Elizabeth Y.] Baylor Coll Med, Dept Med, Infect Dis Sect, Houston, TX 77030 USA. [Chhatwal, Jagpreet] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Chhatwal, Jagpreet] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Cantor, SB (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Hlth Serv Res, Unit 1444, POB 301402, Houston, TX 77230 USA. EM sbcantor@mdanderson.org FU University of Texas MD Anderson Cancer Center; Janice Davis Gordon Memorial Postdoctoral Fellowship in Colorectal Cancer Prevention; National Institutes of Health through The University of Texas MD Anderson Cancer Center [CA016672]; National Cancer Institute [R01 CA163103] FX This research was supported in part by a fellowship for Ashish A. Deshmukh supported by a grant from The University of Texas MD Anderson Cancer Center, Janice Davis Gordon Memorial Postdoctoral Fellowship in Colorectal Cancer Prevention, the National Institutes of Health through The University of Texas MD Anderson Cancer Center Support Grant [CA016672], and the National Cancer Institute (R01 CA163103). NR 33 TC 3 Z9 3 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 15 PY 2015 VL 61 IS 10 BP 1527 EP 1535 DI 10.1093/cid/civ628 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA CW7EW UT WOS:000365161800007 PM 26223993 ER PT J AU Desai, R Savechenkov, PY Zolkowska, D Le Ge, R Rogawski, MA Bruzik, KS Forman, SA Raines, DE Miller, KW AF Desai, Rooma Savechenkov, Pavel Y. Zolkowska, Dorota Le Ge, Ri Rogawski, Michael A. Bruzik, Karol S. Forman, Stuart A. Raines, Douglas E. Miller, Keith W. TI Contrasting actions of a convulsant barbiturate and its anticonvulsant enantiomer on the alpha(1)beta(3)gamma(2L) GABA(A) receptor account for their in vivo effects SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTORS; RAT HIPPOCAMPAL-NEURONS; KINETIC-PROPERTIES; BINDING-SITE; GLUTAMATE RECEPTORS; INTERMEDIATE STATES; DEPRESSANT DRUGS; CHLORIDE CURRENT; A RECEPTORS; ACID AB Most barbiturates are anaesthetics but a few unexpectedly are convulsants. We recently located the anaesthetic sites on GABA(A) receptors (GABA(A)Rs) by photolabelling with an anaesthetic barbiturate. To apply the same strategy to locate the convulsant sites requires the creation and mechanistic characterization of a suitable agent. We synthesized enantiomers of a novel, photoactivable barbiturate, 1-methyl-5-propyly-5-(m-trifluoromethyldiazirinyl) phenyl barbituric acid (mTFD-MPPB). In mice, S-mTFD-MPPB acted as a convulsant, whereas R-mTFD-MPPB acted as an anticonvulsant. Using patch clamp electrophysiology and fast solution exchange on recombinant human (132L) GABA(A)Rs expressed in HEK cells, we found that S-mTFD-MPPB inhibited GABA-induced currents, whereas R-mTFD-MPPB enhanced them. S-mTFD-MPPB caused inhibition by binding to either of two inhibitory sites on open channels with bimolecular kinetics. It also inhibited closed, resting state receptors at similar concentrations, decreasing the channel opening rate and shifting the GABA concentration-response curve to the right. R-mTFD-MPPB, like most anaesthetics, enhanced receptor gating by rapidly binding to allosteric sites on open channels, initiating a rate-limiting conformation change to stabilized open channel states. These states had slower closing rates, thus shifting the GABA concentration-response curve to the left. Under conditions when most GABA(A)Rs were open, an inhibitory action of R-mTFD-MPPB was revealed that had a similar IC50 to that of S-mTFD-MPPB. Thus, the inhibitory sites are not enantioselective, and the convulsant action of S-mTFD-MPPB results from its negligible affinity for the enhancing, anaesthetic sites. Interactions with these two classes of barbiturate binding sites on GABA(A)Rs underlie the enantiomers' different pharmacological activities in mice. C1 [Desai, Rooma; Le Ge, Ri; Forman, Stuart A.; Raines, Douglas E.; Miller, Keith W.] Massachusetts Gen Hosp, Dept Anaesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Savechenkov, Pavel Y.; Bruzik, Karol S.] Univ Illinois, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA. [Zolkowska, Dorota; Rogawski, Michael A.] Univ Calif Davis, Sch Med, Dept Neurol, Sacramento, CA 95817 USA. [Miller, Keith W.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Miller, KW (reprint author), Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA. EM k_miller@helix.mgh.harvard.edu RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 FU National Institute of General Medical Sciences [GM 58448]; National Institute of Neurological Disorders and Stroke [NS079202]; Department of Anaesthesia, Critical Care and Pain Medicine, MGH FX Funded by grants from the National Institute of General Medical Sciences (GM 58448 to K.W.M.) and the National Institute of Neurological Disorders and Stroke (NS079202 to M.A.R.), and by the Department of Anaesthesia, Critical Care and Pain Medicine, MGH. NR 71 TC 2 Z9 2 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3751 EI 1469-7793 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD NOV 15 PY 2015 VL 593 IS 22 BP 4943 EP 4961 DI 10.1113/JP270971 PG 19 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA CW8RU UT WOS:000365267700009 PM 26378885 ER PT J AU Carroll, BJ Shah, RV Murthy, V McCullough, SA Reza, N Thomas, SS Song, TH Newton-Cheh, CH Camuso, JM MacGillivray, T Sundt, TM Semigran, MJ Lewis, GD Baker, JN Garcia, JP AF Carroll, Brett J. Shah, Ravi V. Murthy, Venkatesh McCullough, Stephen A. Reza, Nosheen Thomas, Sunu S. Song, Tae H. Newton-Cheh, Christopher H. Camuso, Janice M. MacGillivray, Thomas Sundt, Thoralf M. Semigran, Marc J. Lewis, Gregory D. Baker, Joshua N. Garcia, Jose P. TI Clinical Features and Outcomes in Adults With Cardiogenic Shock Supported by Extracorporeal Membrane Oxygenation SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID HOSPITAL CARDIAC-ARREST; LIFE-SUPPORT; PULMONARY-EMBOLISM; CARDIOPULMONARY-RESUSCITATION; PROPENSITY ANALYSIS; SURVIVAL; EXPERIENCE; INTERVENTION; FAILURE; TRENDS AB Extracorporeal membrane oxygenation (ECMO) is an increasingly used supportive measure for patients with refractory cardiogenic shock (CS). Despite its increasing use, there remain minimal data regarding which patients with refractory CS are most likely to benefit from ECMO. We retrospectively studied all patients (n = 123) who underwent initiation of ECMO for CS from February 2009 to September 2014 at a single center. Baseline patient characteristics, including demographics, co-morbid illness, cause of CS, available laboratory values, and patient outcomes were analyzed. Overall, 69 patients (56%) were weaned from ECMO, with 48 patients (39%) surviving to discharge. Survivors were younger (50 vs 60 years; p <= 0.0001), had a lower rate of previous smoking (27 vs 56%; p = 0.01) and chronic kidney disease (2% vs 13%; p = 0.03), and had lower lactate measured soon after ECMO initiation (3.1 vs 10.2 mmol/l; p = 0.01). Patients with pulmonary embolism (odds ratio 8.0, 95% confidence interval 2.00 to 31.99; p = 0.01) and acute cardiomyopathy (odds ratio 7.5, 95% confidence interval 1.69 to 33.27; p = 0.01) had a higher rate of survival than acute myocardial infarction, chronic cardiomyopathy, and miscellaneous etiologies compared to postcardiotomy CS as a referent. In conclusion, survival after ECMO initiation differs based on underlying cause of CS. Survival may be lower in older patients and those with early evidence of persistent hypoperfusion after initiation of ECMO for CS. (C) 2015 Elsevier Inc. All rights reserved. C1 [Carroll, Brett J.; Shah, Ravi V.] Harvard Univ, Beth Israel Deaconess Med Ctr, Div Cardiol, Sch Med, Boston, MA 02215 USA. [Shah, Ravi V.; Thomas, Sunu S.; Newton-Cheh, Christopher H.; Semigran, Marc J.; Lewis, Gregory D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [McCullough, Stephen A.; Reza, Nosheen] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Song, Tae H.; Camuso, Janice M.; MacGillivray, Thomas; Sundt, Thoralf M.; Baker, Joshua N.; Garcia, Jose P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiac Surg, Boston, MA 02115 USA. [Murthy, Venkatesh] Univ Michigan, Div Cardiol, Ann Arbor, MI 48109 USA. RP Garcia, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiac Surg, Boston, MA 02115 USA. EM jgarcia@mgh.harvard.edu RI Murthy, Venkatesh/B-3448-2013 OI Murthy, Venkatesh/0000-0002-7901-1321 FU American Heart Association (Dallas, Texas); Massachusetts General Hospital Cardiology Hassenfield Research Scholar Fund (Boston, Massachusetts) FX Dr. Shah receives funding from an American Heart Association Fellow-to-Faculty Award (Dallas, Texas). Dr. Lewis receives funding provided by the Massachusetts General Hospital Cardiology Hassenfield Research Scholar Fund (Boston, Massachusetts). Dr. Garcia received honoraria from Thoratec Corporation and HeartWare Incorporated and serves as a member of the Data and Safety Monitoring Board for CardiacAssist Incorporated. The other authors have no relevant disclosures. NR 30 TC 4 Z9 5 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 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 15 PY 2015 VL 116 IS 10 BP 1624 EP 1630 DI 10.1016/j.amjcard.2015.08.030 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CW7AU UT WOS:000365151100023 PM 26443560 ER PT J AU Galetta, KM Gilden, D AF Galetta, Kristin M. Gilden, Don TI Zeroing in on zoster: A tale of many disorders produced by one virus SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Review DE Varicella-zoster virus; Infection; Vaccination; Neurologic disease ID ISCHEMIC OPTIC NEUROPATHY; TEMPORAL ARTERY INFECTION; STEM-CELL TRANSPLANTATION; HUMAN TRIGEMINAL GANGLIA; HERPES-ZOSTER; OLDER-ADULTS; LONG-TERM; POSTHERPETIC NEURALGIA; VARICELLA VACCINE; VZV VASCULOPATHY AB While herpes zoster infection has been recognized since antiquity, chickenpox (varicella) was confused with smallpox until the 1800s, when both illnesses became better understood. In the 20th century, varicella zoster virus (VZV) was shown to cause varicella upon primary (first-time) infection and herpes zoster (shingles) after reactivation of latent VZV. Scientific progress over the past 50 years has rapidly advanced the understanding and prevention of disease produced by VZV. Combined imaging and virological studies continue to reveal the protean neurological, ocular and visceral disorders produced by VZV. (C) 2015 Elsevier B.V. All rights reserved. C1 [Galetta, Kristin M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Brigham & Womens Hosp,Dept Neurol, Boston, MA USA. [Gilden, Don] Univ Colorado, Sch Med, Dept Neurol, Aurora, CO 80045 USA. [Gilden, Don] Univ Colorado, Sch Med, Dept Immunol & Microbiol, Aurora, CO 80045 USA. RP Gilden, D (reprint author), Univ Colorado, Sch Med, Dept Neurol, 12700 East 19th Ave,Box B82, Aurora, CO 80045 USA. EM don.gilden@ucdenver.edu FU Public Health Service from the National Institutes of Health [AG032958, NS093716] FX This work was supported in part by Public Health Service grants AG032958 (D.G.) and NS093716 (D.G.) from the National Institutes of Health. The authors thank Marina Hoffman for editorial assistance and Cathy Allen for the word processing and formatting of the manuscript. NR 85 TC 1 Z9 1 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X EI 1878-5883 J9 J NEUROL SCI JI J. Neurol. Sci. PD NOV 15 PY 2015 VL 358 IS 1-2 BP 38 EP 45 DI 10.1016/j.jns.2015.10.004 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA CW5PZ UT WOS:000365050200006 PM 26454371 ER PT J AU Rajamuthiah, R Jayamani, E Majed, H Conery, AL Kim, W Kwon, B Fuchs, BB Kelso, MJ Ausubel, FM Mylonakis, E AF Rajamuthiah, Rajmohan Jayamani, Elamparithi Majed, Hiwa Conery, Annie L. Kim, Wooseong Kwon, Bumsup Fuchs, Beth Burgwyn Kelso, Michael J. Ausubel, Frederick M. Mylonakis, Eleftherios TI Antibacterial properties of 3-(phenylsulfonyl)-2-pyrazinecarbonitrile SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Staphylococcus aureus; MRSA; ESKAPE; C. elegans; High throughput screening; Liquid infection assay; Efflux pump inhibition; Synergism ID PSEUDOMONAS-AERUGINOSA; CAENORHABDITIS-ELEGANS; INTRINSIC RESISTANCE; EFFLUX PUMP(S); INFECTION; PATHOGENS; POLYMYXIN AB The emergence of multidrug-resistant bacterial strains has heightened the need for new antimicrobial agents based on novel chemical scaffolds that are able to circumvent current modes of resistance. We recently developed a whole-animal drug-screening methodology in pursuit of this goal and now report the discovery of 3-(phenylsulfonyl)-2-pyrazinecarbonitrile (PSPC) as a novel antibacterial effective against resistant nosocomial pathogens. The minimum inhibitory concentrations (MIC) of PSPC against Staphylococcus aureus and Enterococcus faecium were 4 mu g/mL and 8 mu g/mL, respectively, whereas the MICs were higher against the Gram-negative bacteria Klebsiella pneumoniae (64 mu g/mL), Acinetobacter baumannii (32 mu g/mL), Pseudomonas aeruginosa (>64 mu g/mL), and Enterobacter spp. (>64 mu g/mL). However, co-treatment of PSPC with the efflux pump inhibitor phenylalanine arginyl beta-naphthylamide (PA beta N) or with sub-inhibitory concentrations of the lipopeptide antibiotic polymyxin B reduced the MICs of PSPC against the Gram-negative strains by >4-fold. A sulfide analog of PSPC (PSPC-1S) showed no antibacterial activity, whereas the sulfoxide analog (PSPC-6S) showed identical activity as PSPC across all strains, confirming structure-dependent activity for PSPC and suggesting a target-based mechanism of action. PSPC displayed dose dependent toxicity to both Caenorhabditis elegans and HEK-293 mammalian cells, culminating with a survival rate of 16% (100 mu g/mL) and 8.5% (64 mu g/mL), respectively, at the maximum tested concentration. However, PSPC did not result in hemolysis of erythrocytes, even at a concentration of 64 mu g/mL. Together these results support PSPC as a new chemotype suitable for further development of new antibiotics against Gram-positive and Gram-negative bacteria. (C) 2015 Elsevier Ltd. All rights reserved. C1 [Rajamuthiah, Rajmohan; Jayamani, Elamparithi; Kim, Wooseong; Fuchs, Beth Burgwyn; Mylonakis, Eleftherios] Brown Univ, Alpert Med Sch, Rhode Isl Hosp, Div Infect Dis, Providence, RI 02903 USA. [Rajamuthiah, Rajmohan; Jayamani, Elamparithi; Conery, Annie L.; Ausubel, Frederick M.; Mylonakis, Eleftherios] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kwon, Bumsup] Brown Univ, Alpert Med Sch, Rhode Isl Hosp, Div Neurol, Providence, RI 02903 USA. [Majed, Hiwa; Kelso, Michael J.] Univ Wollongong, Illawarra Hlth & Med Res Inst, Wollongong, NSW 2522, Australia. [Majed, Hiwa; Kelso, Michael J.] Univ Wollongong, Sch Chem, Wollongong, NSW 2522, Australia. RP Mylonakis, E (reprint author), Brown Univ, Alpert Med Sch, Rhode Isl Hosp, Div Infect Dis, 3rd Floor,Suite 328-330,593 Eddy St, Providence, RI 02903 USA. EM emylonakis@lifespan.org RI Kim, Wooseong/A-9256-2017; OI Kim, Wooseong/0000-0002-4597-8374; Kelso, Michael/0000-0001-7809-6637 FU National Institutes of Health [P01 AI083214]; NIH [R01 AI085581]; Boehringer Ingelheim GmbH (Ridgefield, CT) FX This study was supported by National Institutes of Health Grant P01 AI083214 to E.M. and F.M.A., by NIH Grant R01 AI085581 to F.M.A., and by funding from Boehringer Ingelheim GmbH (Ridgefield, CT) to E.M. and F.M.A. NR 22 TC 3 Z9 3 U1 3 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X EI 1464-3405 J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD NOV 15 PY 2015 VL 25 IS 22 BP 5203 EP 5207 DI 10.1016/j.bmcl.2015.09.066 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA CV8KT UT WOS:000364535000037 PM 26459212 ER PT J AU Deshpande, NA Braun, IM Meyer, FL AF Deshpande, Neha A. Braun, Ilana M. Meyer, Fremonta L. TI Impact of fertility preservation counseling and treatment on psychological outcomes among women with cancer: A systematic review SO CANCER LA English DT Review DE decisional regret; fertility preservation counseling; oncofertility; quality of life; satisfaction ID QUALITY-OF-LIFE; BREAST-CANCER; YOUNG-WOMEN; AMERICAN-SOCIETY; EXPERIENCE; SURVIVORS; ISSUES; UPDATE; NEEDS AB BACKGROUNDFor many female cancer survivors, the preservation of reproductive potential is central to quality of life (QOL), and concerns regarding infertility may affect treatment decisions. Despite the existence of several consensus guidelines supporting routine fertility preservation consultation, to the authors' knowledge little is known regarding psychological outcomes in female cancer patients who undergo fertility preservation counseling/consultation (FPC), with or without fertility preservation (FP). METHODSThis literature review examined the effect of FPC alone, or with FP, on psychological outcomes including satisfaction, decisional regret, and QOL. PubMed and PsychINFO were systematically searched for English-language publications from the earliest available publication date of each database through March 2015. Among 111 unique articles concerning oncofertility, 13 met inclusion criteria: peer-reviewed articles reporting primary data regarding satisfaction and psychological outcomes among women who underwent FPC alone or with FP. RESULTSA majority of women receiving FPC reported that the possibility of FP was instrumental to improved coping. Receiving FPC reduced long-term regret and dissatisfaction concerning fertility, and was associated with improved physical QOL and trends toward improved psychological QOL. Women also desired prompt, standardized, and written information addressing perceived unmet needs specific to oncofertility. Offering FPC was perceived as critical regardless of age or parity. CONCLUSIONSTo the best of the authors' knowledge, little research to date has addressed the impact of FPC alone, or with FP, on QOL in women with cancer. Clinicians should recognize the existing evidence base supporting the psychological benefit of prompt FPC. Future research must be conducted to elucidate the long-term psychosocial effects of FP. Cancer 2015;121:3938-3947. (c) 2015 American Cancer Society. Fertility preservation counseling should be offered to all premenopausal women with a recent cancer diagnosis in a timely manner, regardless of parity. Fertility preservation counseling reduces decisional conflict and regret and may improve long-term quality of life, satisfaction, and mental health. C1 [Deshpande, Neha A.; Braun, Ilana M.; Meyer, Fremonta L.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Deshpande, Neha A.] Hosp Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. [Braun, Ilana M.; Meyer, Fremonta L.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Braun, Ilana M.; Meyer, Fremonta L.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02215 USA. RP Meyer, FL (reprint author), Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, 450 Brookline Ave,DA2016A, Boston, MA 02215 USA. EM fremonta_meyer@dfci.harvard.edu NR 23 TC 9 Z9 9 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD NOV 15 PY 2015 VL 121 IS 22 BP 3938 EP 3947 DI 10.1002/cncr.29637 PG 10 WC Oncology SC Oncology GA CV9ST UT WOS:000364627600006 PM 26264701 ER PT J AU Buchbinder, EI Sosman, JA Lawrence, DP McDermott, DF Ramaiya, NH Van den Abbeele, AD Linette, GP Giobbie-Hurder, A Hodi, FS AF Buchbinder, Elizabeth I. Sosman, Jeffrey A. Lawrence, Donald P. McDermott, David F. Ramaiya, Nikhil H. Van den Abbeele, Annick D. Linette, Gerald P. Giobbie-Hurder, Anita Hodi, F. Stephen TI Phase 2 study of sunitinib in patients with metastatic mucosal or acral melanoma SO CANCER LA English DT Article DE acral melanoma; KIT; mucosal melanoma; sunitinib; vascular endothelial growth factor (VEGF) ID GASTROINTESTINAL STROMAL TUMOR; RENAL-CELL CARCINOMA; IMATINIB MESYLATE; II TRIAL; MALIGNANT-MELANOMA; CLINICAL-EFFICACY; MUTATED MELANOMA; KIT; BEVACIZUMAB; SURVIVAL AB BACKGROUNDPatients with mucosal and acral melanomas have limited treatment options and a poor prognosis. Mutations of the KIT oncogene in these melanoma subtypes provide a potential therapeutic target. METHODSA multicenter phase 2 trial of sunitinib was conducted in patients with unresectable stage III or IV melanoma of a mucosal or acral primary origin. Patients were treated in 2 cohorts: cohort A received sunitinib at a dose of 50 mg daily for 4 weeks of a 6-week cycle, and cohort B received sunitinib at a dose of 37.5 mg daily on a continuous basis. Dose reductions were permitted for treatment-related toxicities, and tumor assessments were performed every 2 months. RESULTSFifty-two patients were enrolled: 21 in cohort A and 31 in cohort B. Four patients had confirmed partial responses, which lasted 5 to 10 months (1 with a KIT mutation). In both cohorts, the proportion of patients alive and progression-free at 2 months was 52% (95% confidence interval, 38%-66%); this was significantly larger than the hypothesized null of 5%. There was no significant difference in response or overall survival between the 25% of patients with a KIT mutation and those without one (response rate, 7.7% vs 9.7%; overall survival, 6.4 vs 8.6 months). The overall disease control rate was 44%, and a high rate of toxicity was associated with the treatment. CONCLUSIONSSunitinib showed activity in the treatment of mucosal and acral melanoma that was not dependent on the presence of a KIT mutation. However, the medication was poorly tolerated, and there were no prolonged responses. Cancer 2015;121:4007-4015. (c) 2015 American Cancer Society. Sunitinib has activity in the treatment of mucosal and acral melanoma that is not dependent on the presence of a KIT mutation. However, the medication is poorly tolerated, and there are no prolonged responses. C1 [Buchbinder, Elizabeth I.; Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Sosman, Jeffrey A.] Vanderbilt Univ, Hematol Oncol, Nashville, TN 37235 USA. [Lawrence, Donald P.] Massachusetts Gen Hosp, Hematol Oncol, Boston, MA 02114 USA. [McDermott, David F.] Beth Israel Deaconess Med Ctr, Hematol Oncol, Boston, MA 02215 USA. [Ramaiya, Nikhil H.] Dana Farber Canc Inst, Radiat Oncol, Boston, MA 02115 USA. [Van den Abbeele, Annick D.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Van den Abbeele, Annick D.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Linette, Gerald P.] Washington Univ, Hematol Oncol, St Louis, MO USA. [Giobbie-Hurder, Anita] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Hodi, FS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM stephen_hodi@dfci.harvard.edu FU Pfizer FX Pfizer provided clinical trial support. NR 40 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD NOV 15 PY 2015 VL 121 IS 22 BP 4007 EP 4015 DI 10.1002/cncr.29622 PG 9 WC Oncology SC Oncology GA CV9ST UT WOS:000364627600014 PM 26264378 ER PT J AU Hoos, A Wolchok, JD Humphrey, RW Hodi, FS AF Hoos, Axel Wolchok, Jedd D. Humphrey, Rachel W. Hodi, F. Stephen TI CCR 20th Anniversary Commentary: Immune-Related Response Criteria-Capturing Clinical Activity in Immuno-Oncology SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID CANCER-IMMUNOTHERAPY; DOUBLE-BLIND; PHASE-II; IPILIMUMAB; COMBINATION; CARBOPLATIN; PACLITAXEL; PARADIGM; BLOCKADE; MELANOMA AB To evaluate antitumor responses to chemotherapeutic agents, investigators would typically rely upon Response Evaluation Criteria in Solid Tumors (RECIST) or modified WHO criteria, which do not comprehensively capture responses with immunotherapeutic agents. In the December 1, 2009, issue of Clinical Cancer Research, Wolchok and colleagues reported their development of novel criteria, designated "Immune-related Response Criteria" (irRC), designed to better capture the response patterns observed with immunotherapies. Broad use of the irRC since then has allowed for a more comprehensive evaluation of immunotherapies in clinical trials, indicating that their concepts can be used in conjunction with either RECIST or WHO, and has shown irRC to be a powerful tool for improved clinical investigation. (C) 2015 AACR. C1 [Hoos, Axel] GlaxoSmithKline, Collegeville, PA 19426 USA. [Hoos, Axel; Wolchok, Jedd D.] Canc Immunotherapy Consortium, New York, NY USA. [Wolchok, Jedd D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Humphrey, Rachel W.] CytomX, San Francisco, CA USA. [Hodi, F. Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hoos, A (reprint author), GlaxoSmithKline, Oncol R&D, 1250 South Collegeville Rd, Collegeville, PA 19426 USA. EM Axel.x.Hoos@gsk.com NR 17 TC 10 Z9 13 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2015 VL 21 IS 22 BP 4989 EP 4991 DI 10.1158/1078-0432.CCR-14-3128 PG 3 WC Oncology SC Oncology GA CV7XB UT WOS:000364488700001 PM 26567357 ER PT J AU Letai, A AF Letai, Anthony TI Cell Death and Cancer Therapy: Don't Forget to Kill the Cancer Cell! SO CLINICAL CANCER RESEARCH LA English DT Article ID ADVANCED BREAST-CANCER; LEUKEMIA GROUP-B; BCL-2 FAMILY; NEOADJUVANT CHEMOTHERAPY; MITOCHONDRIAL APOPTOSIS; PATHOLOGICAL RESPONSE; LYMPHOCYTIC-LEUKEMIA; UNTREATED MELANOMA; PROLIFERATION RATE; SMAC MIMETICS AB In our current age of targeted therapies, there is understandably considerable attention paid to the specific molecular targets of pharmaceutical intervention. For a targeted drug to work, it must bind to a target selectively and impair its function. Monitoring biomarkers of the impaired target function can provide vital in vivo pharmacodynamic information. Moreover, genetic changes to the target are often the source of resistance to targeted agents. However, for the treatment of cancer, it is necessary that the therapy not only provide efficient binding and inhibition of the target, but also that this intervention reliably kills the cancer cell. In this CCR Focus section, four articles make the connection between therapies that target T-cell activation, autophagy, IAP proteins, and BCL-2 and the commitment of cancer cells to cell death. Before addressing those exciting classes of targeted therapies, however, an overview is provided to discuss cell death induced by what is arguably still the most successful set of drugs in the history of medical oncology, conventional chemotherapy. (C) 2015 AACR. C1 [Letai, Anthony] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Letai, A (reprint author), Dana Farber Canc Inst, Mayer 430,450 Brookline Ave, Boston, MA 02215 USA. EM anthony_letai@dfci.harvard.edu FU AbbVie; AstraZeneca; Tetralogic FX A. Letai reports receiving commercial research grants from and is a consultant/advisory board member for AbbVie, AstraZeneca, and Tetralogic, and is listed as a co-inventor on pending patent applications, which are owned by Dana-Farber Cancer Institute, related to BH3 profiling. No other potential conflicts of interest were disclosed. NR 48 TC 1 Z9 1 U1 2 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2015 VL 21 IS 22 BP 5015 EP 5020 DI 10.1158/1078-0432.CCR-15-1204 PG 6 WC Oncology SC Oncology GA CV7XB UT WOS:000364488700008 PM 26567360 ER PT J AU Gibson, CJ Davids, MS AF Gibson, Christopher J. Davids, Matthew S. TI BCL-2 Antagonism to Target the Intrinsic Mitochondrial Pathway of Apoptosis SO CLINICAL CANCER RESEARCH LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; BH3 MIMETIC ABT-199; CELL LUNG-CANCER; RANDOMIZED PHASE-II; MULTIPLE-MYELOMA; OBLIMERSEN SODIUM; ANTISENSE OLIGONUCLEOTIDE; OBATOCLAX MESYLATE; FAMILY INHIBITOR AB Despite significant improvements in treatment, cure rates for many cancers remain suboptimal. The rise of cytotoxic chemotherapy has led to curative therapy for a subset of cancers, though intrinsic treatment resistance is difficult to predict for individual patients. The recent wave of molecularly targeted therapies has focused on druggable-activating mutations, and is thus limited to specific subsets of patients. The lessons learned from these two disparate approaches suggest the need for therapies that borrow aspects of both, targeting biologic properties of cancer that are at once distinct from normal cells and yet common enough to make the drugs widely applicable across a range of cancer subtypes. The intrinsic mitochondrial pathway of apoptosis represents one such promising target for new therapies, and successfully targeting this pathway has the potential to alter the therapeutic landscape of therapy for a variety of cancers. Here, we discuss the biology of the intrinsic pathway of apoptosis, an assay known as BH3 profiling that can interrogate this pathway, early attempts to target BCL-2 clinically, and the recent promising results with the BCL-2 antagonist venetoclax (ABT-199) in clinical trials in hematologic malignancies. (C) 2015 AACR. C1 [Gibson, Christopher J.; Davids, Matthew S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Davids, MS (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM matthew_davids@dfci.harvard.edu FU NIH [T32HL116324]; ASCO Career Development Award FX C.J. Gibson is supported by the NIH under award number T32HL116324. M.S. Davids is supported by an ASCO Career Development Award. NR 69 TC 10 Z9 10 U1 3 U2 14 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2015 VL 21 IS 22 BP 5021 EP 5029 DI 10.1158/1078-0432.CCR-15-0364 PG 9 WC Oncology SC Oncology GA CV7XB UT WOS:000364488700009 PM 26567361 ER PT J AU Schneider, BP Li, L Radovich, M Shen, F Miller, KD Flockhart, DA Jiang, GL Vance, G Gardner, L Vatta, M Bai, SC Lai, DB Koller, D Zhao, FM O'Neill, A Smith, ML Railey, E White, C Partridge, A Sparano, J Davidson, NE Foroud, T Sledge, GW AF Schneider, Bryan P. Li, Lang Radovich, Milan Shen, Fei Miller, Kathy D. Flockhart, David A. Jiang, Guanglong Vance, Gail Gardner, Laura Vatta, Matteo Bai, Shaochun Lai, Dongbing Koller, Daniel Zhao, Fengmin O'Neill, Anne Smith, Mary Lou Railey, Elda White, Carol Partridge, Ann Sparano, Joseph Davidson, Nancy E. Foroud, Tatiana Sledge, George W., Jr. TI Genome-Wide Association Studies for Taxane-Induced Peripheral Neuropathy in ECOG-5103 and ECOG-1199 SO CLINICAL CANCER RESEARCH LA English DT Article ID BREAST-CANCER PATIENTS; CONTAINING REGIMENS; SENSORY NEUROPATHY; PACLITAXEL; ADJUVANT; NEUROTOXICITY; POLYMORPHISMS; REVEALS AB Purpose: Taxane-induced peripheral neuropathy (TIPN) is an important survivorship issue for many cancer patients. Currently, there are no clinically implemented biomarkers to predict which patients might be at increased risk for TIPN. We present a comprehensive approach to identification of genetic variants to predict TIPN. Experimental Design: We performed a genome-wide association study (GWAS) in 3,431 patients from the phase III adjuvant breast cancer trial, ECOG-5103 to compare genotypes with TIPN. We performed candidate validation of top SNPs for TIPN in another phase III adjuvant breast cancer trial, ECOG-1199. Results: When evaluating for grade 3-4 TIPN, 120 SNPs had a P value of <10(-4) from patients of European descent (EA) in ECOG-5103. Thirty candidate SNPs were subsequently tested in ECOG-1199 and SNP rs3125923 was found to be significantly associated with grade 3-4 TIPN (P = 1.7 x 10(-3); OR, 1.8). Race was also a major predictor of TIPN, with patients of African descent (AA) experiencing increased risk of grade 2-4 TIPN (HR, 2.1; P = 5.6 x 10(-16)) and grade 3-4 TIPN(HR, 2.6; P = 1.1 x 10(-11)) compared with others. An SNP in FCAMR, rs1856746, had a trend toward an association with grade 2-4 TIPN in AA patients from the GWAS in ECOG-5103 (OR, 5.5; P = 1.6 x 10(-7)). Conclusions: rs3125923 represents a validated SNP to predict grade 3-4 TIPN. Genetically determined AA race represents the most significant predictor of TIPN. (C) 2015 AACR. C1 [Schneider, Bryan P.; Li, Lang; Radovich, Milan; Shen, Fei; Miller, Kathy D.; Flockhart, David A.; Jiang, Guanglong; Vance, Gail; Gardner, Laura; Vatta, Matteo; Bai, Shaochun; Lai, Dongbing; Koller, Daniel; Foroud, Tatiana] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Zhao, Fengmin; O'Neill, Anne; Partridge, Ann] Dana Farber Canc Inst, Boston, MA 02115 USA. [Smith, Mary Lou; Railey, Elda] Res Advocacy Network, Plano, TX USA. [White, Carol] CB White, Chicago, IL USA. [Sparano, Joseph] Albert Einstein Univ, Montefiore Med Ctr, Bronx, NY USA. [Davidson, Nancy E.] Univ Pittsburgh, Ctr Canc, Pittsburgh, PA USA. [Sledge, George W., Jr.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. RP Schneider, BP (reprint author), Indiana Univ, 535 Barnhill Dr Rt473, Indianapolis, IN 46202 USA. EM bpschnei@iupui.edu FU NIH/NCI [CA23318, CA66636, CA21115, CA49883, CA14958, CA16116, CA39229, CA25224, CA12027, CA32102, CA20319, CA77202]; Susan G. Komen for the Cure; Conquer Cancer Foundation; Breast Cancer Research Foundation FX This study was coordinated by ECOG Group (to R.L. Comis) and supported by NIH/NCI grants CA23318, CA66636, CA21115, CA49883, CA14958, CA16116, CA39229, CA25224, CA12027, CA32102, CA20319, CA77202; Susan G. Komen for the Cure; Conquer Cancer Foundation (to B.P. Schneider); and Breast Cancer Research Foundation (to D. Hayes). NR 29 TC 8 Z9 8 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2015 VL 21 IS 22 BP 5082 EP 5091 DI 10.1158/1078-0432.CCR-15-0586 PG 10 WC Oncology SC Oncology GA CV7XB UT WOS:000364488700016 PM 26138065 ER PT J AU Smith, DH Hicks, RR Johnson, VE Bergstrom, DA Cummings, DM Noble, LJ Hovda, D Whalen, M Ahlers, ST LaPlaca, M Tortella, FC Duhaime, AC Dixon, CE AF Smith, Douglas H. Hicks, Ramona R. Johnson, Victoria E. Bergstrom, Debra A. Cummings, Diana M. Noble, Linda J. Hovda, David Whalen, Michael Ahlers, Stephen T. LaPlaca, Michelle Tortella, Frank C. Duhaime, Ann-Christine Dixon, C. Edward TI Pre-Clinical Traumatic Brain Injury Common Data Elements: Toward a Common Language Across Laboratories SO JOURNAL OF NEUROTRAUMA LA English DT Article DE common data elements; data dictionary; pre-clinical TBI models; traumatic brain injury ID DIFFUSE AXONAL INJURY; CONTROLLED CORTICAL IMPACT; CLOSED-HEAD-INJURY; CEREBRAL BLOOD-FLOW; ACUTE SUBDURAL-HEMATOMA; ADULT-RAT BRAIN; FLUID-PERCUSSION MODEL; LASTING IMPULSE NOISE; ALZHEIMERS-DISEASE; INTRACRANIAL-PRESSURE AB Traumatic brain injury (TBI) is a major public health issue exacting a substantial personal and economic burden globally. With the advent of big data approaches to understanding complex systems, there is the potential to greatly accelerate knowledge about mechanisms of injury and how to detect and modify them to improve patient outcomes. High quality, well-defined data are critical to the success of bioinformatics platforms, and a data dictionary of common data elements (CDEs), as well as unique data elements has been created for clinical TBI research. There is no data dictionary, however, for preclinical TBI research despite similar opportunities to accelerate knowledge. To address this gap, a committee of experts was tasked with creating a defined set of data elements to further collaboration across laboratories and enable the merging of data for meta-analysis. The CDEs were subdivided into a Core module for data elements relevant to most, if not all, studies, and Injury-Model-Specific modules for non-generalizable data elements. The purpose of this article is to provide both an overview of TBI models and the CDEs pertinent to these models to facilitate a common language for preclinical TBI research. C1 [Smith, Douglas H.; Johnson, Victoria E.] Univ Penn, Dept Neurosurg, Philadelphia, PA 19104 USA. [Hicks, Ramona R.] One Mind, Seattle, WA USA. [Hicks, Ramona R.; Bergstrom, Debra A.; Cummings, Diana M.] NINDS, NIH, Bethesda, MD 20892 USA. [Noble, Linda J.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA. [Hovda, David] Univ Calif Los Angeles, Dept Neurosurg, Los Angeles, CA USA. [Whalen, Michael] Massachusetts Gen Hosp, Dept Pediat, Ctr Neurosci, Charlestown, MA USA. [Ahlers, Stephen T.] Naval Med Res Ctr, Operat & Undersea Med Directorate, Silver Spring, MD USA. [LaPlaca, Michelle] Georgia Tech, Dept Biomed Engn, Atlanta, GA USA. [LaPlaca, Michelle] Emory Univ, Atlanta, GA 30322 USA. [Tortella, Frank C.] Walter Reed Army Inst Res, Silver Spring, MD USA. [Duhaime, Ann-Christine] Harvard Univ, Sch Med, Dept Neurosurg, Boston, MA USA. [Dixon, C. Edward] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15260 USA. RP Smith, DH (reprint author), Univ Penn, Dept Neurosurg, 105 Hayden Hall,3320 Smith Walk, Philadelphia, PA 19104 USA. EM smithdou@mail.med.upenn.edu FU U.S. Department of Defense; National Institutes of Health FX We would like to acknowledge the U.S. Department of Defense and the National Institutes of Health who contributed funding for The Federal Interagency Traumatic Brain Injury Research (FIT-BIR) Informatics System. NR 131 TC 11 Z9 11 U1 2 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD NOV 15 PY 2015 VL 32 IS 22 BP 1725 EP 1735 DI 10.1089/neu.2014.3861 PG 11 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA CV6ST UT WOS:000364401500003 PM 26058402 ER PT J AU Stamm, JM Koerte, IK Muehlmann, M Pasternak, O Bourlas, AP Baugh, CM Giwerc, MY Zhu, AN Coleman, MJ Bouix, S Fritts, NG Martin, BM Chaisson, C McClean, MD Lin, AP Cantu, RC Tripodis, Y Stern, RA Shenton, ME AF Stamm, Julie M. Koerte, Inga K. Muehlmann, Marc Pasternak, Ofer Bourlas, Alexandra P. Baugh, Christine M. Giwerc, Michelle Y. Zhu, Anni Coleman, Michael J. Bouix, Sylvain Fritts, Nathan G. Martin, Brett M. Chaisson, Christine McClean, Michael D. Lin, Alexander P. Cantu, Robert C. Tripodis, Yorghos Stern, Robert A. Shenton, Martha E. TI Age at First Exposure to Football Is Associated with Altered Corpus Callosum White Matter Microstructure in Former Professional Football Players SO JOURNAL OF NEUROTRAUMA LA English DT Article DE age at first exposure; American football; corpus callosum; diffusion tensor imaging; repetitive head impacts ID TRAUMATIC BRAIN-INJURY; HEAD IMPACT EXPOSURE; HUMAN CEREBRAL-CORTEX; NEUROPSYCHOMETRIC TESTS; RECURRENT CONCUSSION; UNMYELINATED AXONS; YOUTH FOOTBALL; DIFFUSION; CHILDREN; MILD AB Youth football players may incur hundreds of repetitive head impacts (RHI) in one season. Our recent research suggests that exposure to RHI during a critical neurodevelopmental period prior to age 12 may lead to greater later-life mood, behavioral, and cognitive impairments. Here, we examine the relationship between age of first exposure (AFE) to RHI through tackle football and later-life corpus callosum (CC) microstructure using magnetic resonance diffusion tensor imaging (DTI). Forty retired National Football League (NFL) players, ages 40-65, were matched by age and divided into two groups based on their AFE to tackle football: before age 12 or at age 12 or older. Participants underwent DTI on a 3 Tesla Siemens (TIM-Verio) magnet. The whole CC and five subregions were defined and seeded using deterministic tractography. Dependent measures were fractional anisotropy (FA), trace, axial diffusivity, and radial diffusivity. Results showed that former NFL players in the AFE <12 group had significantly lower FA in anterior three CC regions and higher radial diffusivity in the most anterior CC region than those in the AFE 12 group. This is the first study to find a relationship between AFE to RHI and later-life CC microstructure. These results suggest that incurring RHI during critical periods of CC development may disrupt neurodevelopmental processes, including myelination, resulting in altered CC microstructure. C1 [Stamm, Julie M.; Bourlas, Alexandra P.; Baugh, Christine M.; Fritts, Nathan G.; Chaisson, Christine; Cantu, Robert C.; Tripodis, Yorghos; Stern, Robert A.] Boston Univ, CTE Ctr, Sch Med, Boston, MA 02118 USA. [Stamm, Julie M.; Stern, Robert A.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Bourlas, Alexandra P.; Chaisson, Christine; Tripodis, Yorghos; Stern, Robert A.] Boston Univ, Sch Med, Alzheimers Dis Ctr, Boston, MA 02118 USA. [Cantu, Robert C.; Stern, Robert A.] Boston Univ, Sch Med, Dept Neurosurg, Boston, MA 02118 USA. [Stern, Robert A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Stamm, Julie M.; Koerte, Inga K.; Muehlmann, Marc; Pasternak, Ofer; Giwerc, Michelle Y.; Zhu, Anni; Coleman, Michael J.; Bouix, Sylvain; Lin, Alexander P.; Shenton, Martha E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Psychiat Neuroimaging Lab, Boston, MA 02115 USA. [Lin, Alexander P.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Clin Spect, Boston, MA 02115 USA. [Pasternak, Ofer] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Koerte, Inga K.; Muehlmann, Marc] Univ Munich, Dept Child & Adolescent Psychiat Psychosomat & Ps, Munich, Germany. [Baugh, Christine M.] Harvard Univ, Interfac Initiat Hlth Policy, Boston, MA 02115 USA. [Martin, Brett M.; Chaisson, Christine] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA 02118 USA. [Chaisson, Christine; Tripodis, Yorghos] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. [McClean, Michael D.] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02118 USA. [Cantu, Robert C.] Sports Legacy Inst, Waltham, MA USA. [Cantu, Robert C.] Emerson Hosp, Dept Neurosurg, Concord, MA USA. [Shenton, Martha E.] VA Boston Healthcare Syst, Brockton Div, Brockton, MA USA. RP Stern, RA (reprint author), Boston Univ, CTE Ctr, Sch Med, 72 East Concord St,B7800, Boston, MA 02118 USA. EM bobstern@bu.edu OI Tripodis, Yorghos/0000-0003-2190-7608 FU National Institutes of Health [R01 NS 078337, F31 NS 081957, P30 AG13846, UL1-TR000157, P41 EB015902, T32MH019733]; JetBlue Airlines; National Football League (NFL); NFL Players Association; Else Kroner-Fresenius Foundation, Germany; VA Merit Award FX The authors extend their appreciation to the study participants who make this work possible. This study was supported by the National Institutes of Health (R01 NS 078337; F31 NS 081957 [J.M.S.]; P30 AG13846; UL1-TR000157, P41 EB015902 [O.P.]; T32MH019733 [C.M.B.]), and participant travel was funded by gifts from JetBlue Airlines, the National Football League (NFL), and the NFL Players Association. This study was also partly supported by the Else Kroner-Fresenius Foundation, Germany (I.K., M.M.), and by a VA Merit Award (M.E.S., M.C., L.L., A.Z.). NR 77 TC 11 Z9 11 U1 8 U2 29 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD NOV 15 PY 2015 VL 32 IS 22 BP 1768 EP 1776 DI 10.1089/neu.2014.3822 PG 9 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA CV6ST UT WOS:000364401500007 PM 26200068 ER PT J AU Silva, PPB Bhatnagar, S Herman, SD Zafonte, R Klibanski, A Miller, KK Tritos, NA AF Silva, Paula P. B. Bhatnagar, Saurabha Herman, Seth D. Zafonte, Ross Klibanski, Anne Miller, Karen K. Tritos, Nicholas A. TI Predictors of Hypopituitarism in Patients with Traumatic Brain Injury SO JOURNAL OF NEUROTRAUMA LA English DT Article DE adrenal insufficiency; diabetes insipidus; growth hormone deficiency; hypogonadism; hypopituitarism; hypothyroidism; traumatic brain injury ID ANEURYSMAL SUBARACHNOID HEMORRHAGE; ANTERIOR-PITUITARY FUNCTION; GROWTH-HORMONE DEFICIENCY; INSULIN TOLERANCE-TEST; ADULT GH DEFICIENCY; BODY-MASS INDEX; NEUROENDOCRINE DYSFUNCTION; HEAD TRAUMA; ACUTE-PHASE; PREVALENCE AB Hypopituitarism may often occur in association with traumatic brain injury (TBI). Identification of reliable predictors of pituitary dysfunction is of importance in order to establish a rational testing approach. We searched the records of patients with TBI, who underwent neuroendocrine evaluation in our institution between 2007 and 2013. One hundred sixty-six adults (70% men) with TBI (median age: 41.6 years; range: 18-76) were evaluated at a median interval of 40.4 months (0.2-430.4).Of these, 31% had 1 pituitary deficiency, including 29% of patients with mild TBI and 35% with moderate/severe TBI. Growth hormone deficiency was the most common deficiency (21%); when body mass index (BMI)-dependent cutpoints were used, this was reduced to 15%. Central hypoadrenalism occurred in10%, who were more likely to have suffered a motor vehicle accident (MVA, p=0.04), experienced post-traumatic seizures (p=0.04), demonstrated any intracranial hemorrhage (p=0.05), petechial brain hemorrhages (p=0.017), or focal cortical parenchymal contusions (p=0.02). Central hypothyroidism occurred in 8% and central hypogonadism in 12%; the latter subgroup had higher BMI (p=0.03), were less likely to be working after TBI (p=0.002), and had lower Global Assessment of Functioning (GAF) scores (p=0.03). Central diabetes insipidus (DI) occurred in 6%, who were more likely to have experienced MVA (p<0.001) or sustained moderate/severe TBI (p<0.001). Patients with MVA and those with post-traumatic seizures, intracranial hemorrhage, petechial brain hemorrhages, and/or focal cortical contusions are at particular risk for serious pituitary dysfunction, including adrenal insufficiency and DI, and should be referred for neuroendocrine testing. However, a substantial proportion of patients without these risk factors also developed hypopituitarism. C1 [Silva, Paula P. B.; Klibanski, Anne; Miller, Karen K.; Tritos, Nicholas A.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Bhatnagar, Saurabha; Herman, Seth D.; Zafonte, Ross] Massachusetts Gen Hosp, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Bhatnagar, Saurabha; Herman, Seth D.; Zafonte, Ross] Harvard Univ, Sch Med, Boston, MA USA. RP Tritos, NA (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Zero Emerson Pl 112, Boston, MA 02114 USA. EM ntritos@mgh.harvard.edu FU NIDILRR TBIMS grants [90DP0039-01-02, W81XWH-08-2-0159] FX No conflicting financial interests exist. The work was supported in part by NIDILRR TBIMS grants nos. 90DP0039-01-02 and W81XWH-08-2-0159. NR 35 TC 2 Z9 2 U1 3 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD NOV 15 PY 2015 VL 32 IS 22 BP 1789 EP 1795 DI 10.1089/neu.2015.3998 PG 7 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA CV6ST UT WOS:000364401500009 PM 26413767 ER PT J AU Bazley, FA Liu, CF Yuan, X Hao, HP All, AH Angeles, AD Zambidis, ET Gearhart, JD Kerr, CL AF Bazley, Faith A. Liu, Cyndi F. Yuan, Xuan Hao, Haiping All, Angelo H. De Los Angeles, Alejandro Zambidis, Elias T. Gearhart, John D. Kerr, Candace L. TI Direct Reprogramming of Human Primordial Germ Cells into Induced Pluripotent Stem Cells: Efficient Generation of Genetically Engineered Germ Cells SO STEM CELLS AND DEVELOPMENT LA English DT Article ID EMBRYONAL CARCINOMA-CELLS; HUMAN SOMATIC-CELLS; HUMAN IPS CELLS; GENE-EXPRESSION; SELF-RENEWAL; IN-VITRO; PREIMPLANTATION DEVELOPMENT; TRANSCRIPTION FACTOR; MESSENGER-RNA; MOUSE TESTIS AB Primordial germ cells (PGCs) share many properties with embryonic stem cells (ESCs) and innately express several key pluripotency-controlling factors, including OCT4, NANOG, and LIN28. Therefore, PGCs may provide a simple and efficient model for studying somatic cell reprogramming to induced pluripotent stem cells (iPSCs), especially in determining the regulatory mechanisms that fundamentally define pluripotency. Here, we report a novel model of PGC reprogramming to generate iPSCs via transfection with SOX2 and OCT4 using integrative lentiviral. We also show the feasibility of using nonintegrative approaches for generating iPSC from PGCs using only these two factors. We show that human PGCs express endogenous levels of KLF4 and C-MYC protein at levels similar to embryonic germ cells (EGCs) but lower levels of SOX2 and OCT4. Transfection with both SOX2 and OCT4 together was required to induce PGCs to a pluripotent state at an efficiency of 1.71%, and the further addition of C-MYC increased the efficiency to 2.33%. Immunohistochemical analyses of the SO-derived PGC-iPSCs revealed that these cells were more similar to ESCs than EGCs regarding both colony morphology and molecular characterization. Although leukemia inhibitory factor (LIF) was not required for the generation of PGC-iPSCs like EGCs, the presence of LIF combined with ectopic exposure to C-MYC yielded higher efficiencies. Additionally, the SO-derived PGC-iPSCs exhibited differentiation into representative cell types from all three germ layers in vitro and successfully formed teratomas in vivo. Several lines were generated that were karyotypically stable for up to 24 subcultures. Their derivation efficiency and survival in culture significantly supersedes that of EGCs, demonstrating their utility as a powerful model for studying factors regulating pluripotency in future studies. C1 [Bazley, Faith A.; All, Angelo H.] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA. [Liu, Cyndi F.; Kerr, Candace L.] Johns Hopkins Univ, Sch Med, Dept Genecol & Obstet, Baltimore, MD USA. [Liu, Cyndi F.; Zambidis, Elias T.] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD USA. [Yuan, Xuan] Johns Hopkins Univ, Sch Med, Dept Med, Div Hematol, Baltimore, MD 21205 USA. [Hao, Haiping] Johns Hopkins Univ, High Throughput Biol Ctr, JHMI Deep Sequencing & Microarray Core, Baltimore, MD USA. [De Los Angeles, Alejandro] Childrens Hosp Boston, Div Pediat Hematol Oncol, Stem Cell Transplantat Program, Boston, MA USA. [De Los Angeles, Alejandro] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [De Los Angeles, Alejandro] Harvard Stem Cell Inst, Cambridge, MA USA. [Zambidis, Elias T.] Johns Hopkins Univ, Sch Med, Div Pediat Oncol, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Gearhart, John D.] Univ Penn, Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. [Gearhart, John D.] Univ Penn, Sch Vet Med, Dept Anim Biol, Philadelphia, PA 19104 USA. [Kerr, Candace L.] Univ Maryland, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA. RP Kerr, CL (reprint author), Univ Maryland, Dept Biochem & Mol Biol, 108 North Greene St, Baltimore, MD 21201 USA. EM ckerr@som.umaryland.edu OI Hao, Haiping/0000-0003-2522-7546 FU NICHD [R21 HD057487]; Maryland Stem Cell Research Funds [2007-MSCRFE-0210-01]; [2008-MSCRFE-0129-00] FX This work was graciously supported by NICHD R21 HD057487 (C.L.K.), Maryland Stem Cell Research Funds 2007-MSCRFE-0210-01 (C.L.K.), and by 2008-MSCRFE-0129-00 (C.L.K.). NR 87 TC 5 Z9 5 U1 1 U2 7 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1547-3287 EI 1557-8534 J9 STEM CELLS DEV JI Stem Cells Dev. PD NOV 15 PY 2015 VL 24 IS 22 BP 2634 EP 2648 DI 10.1089/scd.2015.0100 PG 15 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA CV6SM UT WOS:000364400700003 PM 26154167 ER PT J AU Chunharojrith, P Nakayama, Y Jiang, XB Kery, RE Ma, J Ulloa, CSD Zhang, X Zhou, YL Klibanski, A AF Chunharojrith, Paweena Nakayama, Yuki Jiang, Xiaobing Kery, Rachel E. Ma, Jun Ulloa, Cristine S. De la Hoz Zhang, Xun Zhou, Yunli Klibanski, Anne TI Tumor suppression by MEG3 lncRNA in a human pituitary tumor derived cell line SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE MEG3; Long non-coding RNA; p53; Pituitary tumor; Tumor suppression ID NONCODING RNA MEG3; GENE-EXPRESSION; HISTONE DEACETYLASES; GASTRIC-CANCER; P53 EXPRESSION; CLONAL ORIGIN; T-ANTIGEN; ADENOMAS; HYPERMETHYLATION; PROLIFERATION AB Human clinically non-functioning pituitary adenomas (NFAs) account for approximately 40% of diagnosed pituitary tumors. Epigenetic mutations in tumor suppressive genes play an important role in NFA development. Maternally expressed gene 3 (MEG3) is a long non-coding RNA (IncRNA) and we hypothesized that it is a candidate tumor suppressor whose epigenetic silencing is specifically linked to NFA development. In this study, we introduced MEG3 expression into PDFS cells, derived from a human NFA, using both inducible and constitutively active expression systems. MEG3 expression significantly suppressed xenograft tumor growth in vivo in nude mice. When induced in culture, MEG3 caused cell cycle arrest at the G1 phase. In addition, inactivation of p53 completely abolished tumor suppression by MEG3, indicating that MEG3 tumor suppression is mediated by p53. In conclusion, our data support the hypothesis that MEG3 is a IncRNA tumor suppressor in the pituitary and its inactivation contributes to NFA development. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Zhou, Yunli] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Zhou, YL (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,Bulfinch 457, Boston, MA 02114 USA. EM yunli.zhou@mgh.harvard.edu FU National Institutes of Health [R01DK40947]; Guthart Family Foundation; Jarislowsky Foundation FX This work was supported by grants from the National Institutes of Health (A K, R01DK40947), the Guthart Family Foundation, and the Jarislowsky Foundation. NR 57 TC 8 Z9 8 U1 2 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD NOV 15 PY 2015 VL 416 IS C BP 27 EP 35 DI 10.1016/j.mce.2015.08.018 PG 9 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA CV4WS UT WOS:000364267800004 PM 26284494 ER PT J AU Muralidhar, V Chen, MH Reznor, G Moran, BJ Braccioforte, MH Beard, CJ Feng, FY Hoffman, KE Choueiri, TK Martin, NE Sweeney, CJ Trinh, QD Nguyen, PL AF Muralidhar, Vinayak Chen, Ming-Hui Reznor, Gally Moran, Brian J. Braccioforte, Michelle H. Beard, Clair J. Feng, Felix Y. Hoffman, Karen E. Choueiri, Toni K. Martin, Neil E. Sweeney, Christopher J. Trinh, Quoc-Dien Nguyen, Paul L. TI Definition and Validation of "Favorable High-Risk Prostate Cancer": Implications for Personalizing Treatment of Radiation-Managed Patients SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID ANDROGEN-DEPRIVATION THERAPY; RADICAL PROSTATECTOMY; SHORT-TERM; RADIOTHERAPY; TRIAL; SUPPRESSION; DURATION; STRATIFICATION; DISEASE; MEN AB Purpose: To define and validate a classification of favorable high-risk prostate cancer that could be used to personalize therapy, given that consensus guidelines recommend similar treatments for all radiation-managed patients with high-risk disease. Methods and Materials: We studied 3618 patients with cT1-T3aN0M0 high-risk or unfavorable intermediate-risk prostate adenocarcinoma treated with radiation at a single institution between 1997 and 2013. Favorable high-risk was defined as T1c disease with either Gleason 4 + 4 = 8 and prostate-specific antigen <10 ng/mL or Gleason 6 and prostate-specific antigen >20 ng/mL. Competing risks regression was used to determine differences in the risk of prostate cancerespecific mortality (PCSM) after controlling for baseline factors and treatment. Our results were validated in a cohort of 13,275 patients using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Results: Patients with favorable high-risk disease had significantly better PCSM than other men with high-risk disease (adjusted hazard ratio [AHR] 0.42, 95% confidence interval [CI] 0.18-0.996, P = .049) and similar PCSM as men with unfavorable intermediate-risk disease (AHR 1.17, 95% CI 0.50-2.75, P = .710). We observed very similar results within the SEER-Medicare cohort (favorable high-risk vs other high-risk: AHR 0.21, 95% CI 0.11-0.41, P < .001; favorable high-risk vs unfavorable intermediate-risk: AHR 0.67, 95% CI 0.33-1.36, P = .268). Conclusions: Patients with favorable high-risk prostate cancer have significantly better PCSM than other patients with high-risk disease and similar PCSM as those with unfavorable intermediate-risk disease, who are typically treated with shorter-course androgen deprivation therapy. This new classification system may allow for personalization of treatment within high-risk disease, such as consideration of shorter-course androgen deprivation therapy for favorable high-risk disease. (C) 2015 The Authors. Published by Elsevier Inc. C1 [Muralidhar, Vinayak] Harvard Univ, Sch Med, Harvard Mit Div Hlth Sci & Technol, Boston, MA 02115 USA. [Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Reznor, Gally] Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Moran, Brian J.; Braccioforte, Michelle H.] Prostate Canc Fdn Chicago, Westmont, IL USA. [Beard, Clair J.; Martin, Neil E.; Nguyen, Paul L.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Beard, Clair J.; Martin, Neil E.; Nguyen, Paul L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Feng, Felix Y.] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. [Hoffman, Karen E.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Choueiri, Toni K.; Sweeney, Christopher J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Choueiri, Toni K.; Sweeney, Christopher J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Trinh, Quoc-Dien] Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. RP Nguyen, PL (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu RI Martin, Neil/E-2193-2014 OI Martin, Neil/0000-0002-8164-8516 FU Health Sciences and Technology IDEA2 Program; Peter C. Farrell Fund; Prostate Cancer Foundation; Fitz's Cancer Warriors; David and Cynthia Chapin; Hugh Simons in Honor of Frank and Anne Simons; Scott Forbes and Gina Ventre Fund FX This work was supported by grants from the Health Sciences and Technology IDEA2 Program supported by the Peter C. Farrell (1967) Fund, The Prostate Cancer Foundation, Fitz's Cancer Warriors, David and Cynthia Chapin, Hugh Simons in Honor of Frank and Anne Simons, The Scott Forbes and Gina Ventre Fund, and a grant from an anonymous family foundation. NR 30 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 15 PY 2015 VL 93 IS 4 BP 828 EP 835 DI 10.1016/j.ijrobp.2015.07.2281 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CU0EL UT WOS:000363188700013 PM 26530751 ER PT J AU Wagner, FB Eskandar, EN Cosgrove, GR Madsen, JR Blum, AS Potter, NS Hochberg, LR Cash, SS Truccolo, W AF Wagner, Fabien B. Eskandar, Emad N. Cosgrove, G. Rees Madsen, Joseph R. Blum, Andrew S. Potter, N. Stevenson Hochberg, Leigh R. Cash, Sydney S. Truccolo, Wilson TI Microscale spatiotemporal dynamics during neocortical propagation of human focal seizures SO NEUROIMAGE LA English DT Article DE Epilepsy; Collective dynamics; Secondary generalization; Cortical waves; Neural state segmentation ID EPILEPTIFORM ACTIVITY; MOTOR CORTEX; EPILEPSY; TETRAPLEGIA; PATTERNS; EVENTS; EEG AB Some of the most clinically consequential aspects of focal epilepsy, e.g. loss of consciousness, arise from the generalization or propagation of seizures through local and large-scale neocortical networks. Yet, the dynamics of such neocortical propagation remain poorly understood. Here, we studied the microdynamics of focal seizure propagation in neocortical patches (4 x 4 mm) recorded via high-density microelectrode arrays (MEAs) implanted in people with pharmacologically resistant epilepsy. Our main findings are threefold: (1) a newly developed stage segmentation method, applied to local field potentials (LFPs) and multiunit activity (MUA), revealed a succession of discrete seizure stages, each lasting several seconds. These different stages showed characteristic evolutions in overall activity and spatial patterns, which were relatively consistent across seizures within each of the 5 patients studied. Interestingly, segmented seizure stages based on LFPs or MUA showed a dissociation of their spatiotemporal dynamics, likely reflecting different contributions of non-local synaptic inputs and local network activity. (2) As previously reported, some of the seizures showed a peak in MUA that happened several seconds after local seizure onset and slowly propagated across the MEA. However, other seizures had a more complex structure characterized by, for example, several MUA peaks, more consistent with the succession of discrete stages than the slow propagation of a simple wavefront of increased MUA. In both cases, nevertheless, seizures characterized by spike-wave discharges (SWDs, similar to 2-3 Hz) eventually evolved into patterns of phase-locked MUA and LFPs. (3) Individual SWDs or gamma oscillation cycles (25-60 Hz), characteristic of two different types of recorded seizures, tended to propagate with varying degrees of directionality, directions of propagation and speeds, depending on the identified seizure stage. However, no clear relationship was observed between the MUA peak onset time (in seizures where such peak onset occurred) and changes in MUA or LFP propagation patterns. Overall, our findings indicate that the recruitment of neocortical territories into ictal activity undergoes complex spatiotemporal dynamics evolving in slow discrete states, which are consistent across seizures within each patient. Furthermore, ictal states at finer spatiotemporal scales (individual SWDs or gamma oscillations) are organized by slower time scale network dynamics evolving through these discrete stages. (C) 2015 Elsevier Inc. All rights reserved. C1 [Wagner, Fabien B.; Truccolo, Wilson] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Hochberg, Leigh R.] Brown Univ, Sch Engn, Providence, RI 02912 USA. [Blum, Andrew S.; Potter, N. Stevenson] Brown Univ, Alpert Med Sch, Dept Neurol, Providence, RI 02912 USA. [Cosgrove, G. Rees] Brown Univ, Alpert Med Sch, Dept Neurosurg, Providence, RI 02912 USA. [Hochberg, Leigh R.; Truccolo, Wilson] Brown Univ, Inst Brain Sci, Providence, RI 02912 USA. [Cosgrove, G. Rees] Brown Univ, Norman Prince Neurosci Inst, Providence, RI 02912 USA. [Hochberg, Leigh R.; Truccolo, Wilson] US Dept Vet Affairs, Ctr Neurorestorat & Neurotechnol, Providence, RI USA. [Hochberg, Leigh R.; Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Eskandar, Emad N.; Madsen, Joseph R.; Hochberg, Leigh R.; Cash, Sydney S.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Eskandar, Emad N.] Massachusetts Gen Hosp, Nayef Al Rodhan Labs Cellular Neurosurg & Neurosu, Boston, MA 02114 USA. [Madsen, Joseph R.] Childrens Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Madsen, Joseph R.] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Hochberg, Leigh R.] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02114 USA. RP Wagner, FB (reprint author), Brown Univ, Dept Neurosci, Providence, RI 02912 USA. EM fabien.wagner@epfl.ch; wilson_truccolo@brown.edu FU National Institute of Neurological Disorders and Stroke (NINDS) [R01NS079533, R01NS062092]; Department of Veterans Affairs, Merit Review Award [RX000668-01A2] FX We would like to thank the patients who participated in this study, the nursing and medical staff at Massachusetts General and Rhode Island Hospitals, Omar Ahmed and other members of the Cash lab for helping with data recordings, and Michael Rule for suggesting the use of the similarity matrix for seizure segmentation. This research was supported by: the National Institute of Neurological Disorders and Stroke (NINDS), grants R01NS079533 (to WT), R01NS062092 (to SSC); the Department of Veterans Affairs, Merit Review Award RX000668-01A2 (to WT); and the Pablo J. Salame '88 Goldman Sachs endowed Assistant Professorship of Computational Neuroscience (WT). The contents do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. NR 25 TC 2 Z9 2 U1 0 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD NOV 15 PY 2015 VL 122 BP 114 EP 130 DI 10.1016/j.neuroimage.2015.08.019 PG 17 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CT9GO UT WOS:000363125200013 PM 26279211 ER PT J AU Ganz, M Greve, DN Fischl, B Konukoglu, E AF Ganz, Melanie Greve, Douglas N. Fischl, Bruce Konukoglu, Ender CA Alzheimer's Dis Neuroimaging TI Relevant feature set estimation with a knock-out strategy and random forests SO NEUROIMAGE LA English DT Article DE Multivariate pattern analysis; Interpretability; Relevant features; Random forests; Knock-out ID PARTIAL LEAST-SQUARES; SUPPORT VECTOR MACHINES; VOXEL-BASED MORPHOMETRY; IMAGE-BASED PREDICTION; SURFACE-BASED ANALYSIS; CORTICAL THICKNESS; FEATURE-SELECTION; ALZHEIMERS-DISEASE; CEREBRAL-CORTEX; FMRI DATA AB Group analysis of neuroimaging data is a vital tool for identifying anatomical and functional variations related to diseases as well as normal biological processes. The analyses are often performed on a large number of highly correlated measurements using a relatively smaller number of samples. Despite the correlation structure, the most widely used approach is to analyze the data using univariate methods followed by post-hoc corrections that try to account for the data's multivariate nature. Although widely used, this approach may fail to recover from the adverse effects of the initial analysis when local effects are not strong. Multivariate pattern analysis (MVPA) is a powerful alternative to the univariate approach for identifying relevant variations. Jointly analyzing all the measures, MVPA techniques can detect global effects even when individual local effects are too weak to detect with univariate analysis. Current approaches are successful in identifying variations that yield highly predictive and compact models. However, they suffer from lessened sensitivity and instabilities in identification of relevant variations. Furthermore, current methods' user-defined parameters are often unintuitive and difficult to determine. In this article, we propose a novel MVPA method for group analysis of high-dimensional data that overcomes the drawbacks of the current techniques. Our approach explicitly aims to identify all relevant variations using a "knock-out" strategy and the Random Forest algorithm. In evaluations with synthetic datasets the proposed method achieved substantially higher sensitivity and accuracy than the state-of-the-art MVPA methods, and outperformed the univariate approach when the effect size is low. In experiments with real datasets the proposed method identified regions beyond the univariate approach, while other MVPA methods failed to replicate the univariate results. More importantly, in a reproducibility study with the well-known ADNI dataset the proposed method yielded higher stability and power than the univariate approach. (C) 2015 Elsevier Inc. All rights reserved. C1 [Ganz, Melanie] Rigshosp, Neurobiol Res Unit, DK-2100 Copenhagen, Denmark. [Ganz, Melanie] Rigshosp, Ctr Integrated Mol Brain Imaging, DK-2100 Copenhagen, Denmark. [Ganz, Melanie; Greve, Douglas N.; Fischl, Bruce; Konukoglu, Ender] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Boston, MA 02114 USA. [Ganz, Melanie; Greve, Douglas N.; Fischl, Bruce; Konukoglu, Ender] Harvard Univ, Sch Med, Boston, MA USA. [Fischl, Bruce] MIT, Comp Sci & AI Lab, Div Hlth Sci & Technol, Boston, MA USA. RP Konukoglu, E (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Boston, MA 02114 USA. EM melanie.ganz@nru.dk; enderk@nmr.mgh.harvard.edu OI Ganz, Melanie/0000-0002-9120-8098 FU National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health; NIH Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program [S10RR023401, S10RR019307, S10RR019254, S10RR023043]; Alfred Benzon; Lundbeck Foundation; Carlsberg Foundation; Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]; DOD ADNI (Department of Defense) [W81XWH-12-2-0012]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd; Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; Takeda Pharmaceutical Company; Canadian Institutes Rev Health Research; National Institute of Health Center of Biomedical Research Excellence (COBRE) grant [P20 RR021938-01A2]; [P50 AG05681]; [P01 AG03991]; [R01 AG021910]; [P50 MH071616]; [U24 RR021382]; [R01 MH56584]; [P41 RR014075]; [R01 EB000840]; [R01 EB005846]; [R01 EB006841]; [RC1 MH089257] FX This research was carried out in whole or in part at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41EB015896, a P41 Biotechnology Resource Grant supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health. This work also involved the use of instrumentation supported by the NIH Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program; specifically, grant number(s) S10RR023401, S10RR019307, S10RR019254 and S10RR023043. Melanie Ganz' research was also supported by the Alfred Benzon and the Lundbeck Foundation aswell as the Carlsberg Foundation.; Since OASIS data was used we acknowledge the following grants: P50 AG05681, P01 AG03991, R01 AG021910, P50 MH071616, U24 RR021382, R01 MH56584. Additionally, data collection and sharing for this project were funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes Rev December 5, 2013 Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Next, grant support for the MCIC data study was provided by the federal grants P41 RR014075, R01 EB000840, R01 EB005846, R01 EB006841 and RC1 MH089257. Finally, the COBRE imaging data and phenotypic information was collected and shared by the Mind Research Network and the University of New Mexico funded by a National Institute of Health Center of Biomedical Research Excellence (COBRE) grant, P20 RR021938-01A2. NR 80 TC 2 Z9 2 U1 3 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD NOV 15 PY 2015 VL 122 BP 131 EP 148 DI 10.1016/j.neuroimage.2015.08.006 PG 18 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CT9GO UT WOS:000363125200014 PM 26272728 ER PT J AU Ou, YM Gollub, RL Retzepi, K Reynolds, N Pienaar, R Pieper, S Murphy, SN Grant, PE Zollei, L AF Ou, Yangming Gollub, Randy L. Retzepi, Kallirroi Reynolds, Nathaniel Pienaar, Rudolph Pieper, Steve Murphy, Shawn N. Grant, P. Ellen Zoellei, Lilla TI Brain extraction in pediatric ADC maps, toward characterizing neuro-development in multi-platform and multi-institution clinical images SO NEUROIMAGE LA English DT Article ID APPARENT DIFFUSION-COEFFICIENT; MAGNETIC-RESONANCE IMAGES; WHITE-MATTER DEVELOPMENT; ATLAS-BASED SEGMENTATION; 3D MR-IMAGES; PRETERM INFANTS; QUANTITATIVE-EVALUATION; REGISTRATION TECHNIQUES; SPATIAL NORMALIZATION; TISSUE SEGMENTATION AB Apparent Diffusion Coefficient (ADC) maps can be used to characterize myelination and to detect abnormalities in the developing brain. However, given the normal variation in regional ADC with myelination, detection of abnormalities is difficult when based on visual assessment. Quantitative and automated analysis of pediatric ADC maps is thus desired but requires accurate brain extraction as the first step. Currently, most existing brain extraction methods are optimized for structural T1-weighted MR images of fully myelinated brains. Due to differences in age and image contrast, these approaches do not translate well to pediatric ADC maps. To address this problem, we present a multi-atlas brain extraction framework that has 1) specificity: designed and optimized specifically for pediatric ADC maps; 2) generality: applicable to multi-platform and multi-institution data, and to subjects at various neuro-developmental stages across the first 6 years of life; 3) accuracy: highly accurate compared to expert annotations; and 4) consistency: consistently accurate regardless of sources of data and ages of subjects. We show how we achieve these goals, via optimizing major components in a multi-atlas brain extraction framework, and via developing and evaluating new criteria for its atlas ranking component. Moreover, we demonstrate that these goals can be achieved with a fixed set of atlases and a fixed set of parameters, which opens doors for our optimized framework to be used in large-scale and multi-institution neuro-developmental and clinical studies. In a pilot study, we use this framework in a dataset containing scanner-generated ADC maps from 308 pediatric patients collected during the course of routine clinical care. Our framework leads to successful quantifications of the changes in whole-brain volumes and mean ADC values across the first 6 years of life. (C) 2015 Elsevier Inc. All rights reserved. C1 [Ou, Yangming; Gollub, Randy L.; Retzepi, Kallirroi; Reynolds, Nathaniel] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat Neuroimaging,Dept Psychiat, Charlestown, MA 02129 USA. [Ou, Yangming; Gollub, Randy L.; Retzepi, Kallirroi; Reynolds, Nathaniel; Zoellei, Lilla] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Lab Computat Neuroimaging,Med Sch, Charlestown, MA 02129 USA. [Pienaar, Rudolph; Grant, P. Ellen] Harvard Univ, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Childrens Hosp Boston, Sch Med, Boston, MA 02115 USA. [Pieper, Steve] Isomics Inc, Cambridge, MA 02138 USA. [Murphy, Shawn N.] Partners HealthCare, Res Comp, Charlestown, MA 02129 USA. [Murphy, Shawn N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Comp Sci Lab, Boston, MA 02114 USA. RP Ou, YM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 149 13th St,Rm 2301, Charlestown, MA 02129 USA. EM yangming.ou@mgh.harvard.edu OI Reynolds, Nathaniel/0000-0002-6745-2293; Ou, Yangming/0000-0002-7726-6208 FU [1S10RR023401]; [1S10RR019307]; [1S10RR023043] FX The authors would like to thank Katie Murphy for her extensive and careful reviewing of the radiological reports and patient records, which guaranteed that the pediatric subjects in the PD308 cohort were all normative at the time of the scan. We also thank other members of the mi2b2 team, for the support of RPDR and the mi2b2 workbench, which we used to query and retrieve radiological data for this study: Christopher Herrick, Yanbing Wang, Taowei David Wang, Darren Sack, and Katherine P. Andriole. The authors would also like to acknowledge Instrumentation Grants 1S10RR023401, 1S10RR019307, and 1S10RR023043. NR 142 TC 0 Z9 0 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD NOV 15 PY 2015 VL 122 BP 246 EP 261 DI 10.1016/j.neuroimage.2015.08.002 PG 16 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA CT9GO UT WOS:000363125200025 PM 26260429 ER PT J AU Russo, M Mahon, K Shanahan, M Ramjas, E Solon, C Purcell, SM Burdick, KE AF Russo, Manuela Mahon, Katie Shanahan, Megan Ramjas, Elizabeth Solon, Carly Purcell, Shaun M. Burdick, Katherine E. TI The relationship between sleep quality and neurocognition in bipolar disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Sleep disruption; Sleep quality; Neurocognition; Bipolar disorder ID CLOCK GENES; COGNITIVE DYSFUNCTION; CIRCADIAN-RHYTHMS; SOCIAL COGNITION; RATING-SCALE; DEPRESSION; PREFERENCE; RISK; SCHIZOPHRENIA; INDIVIDUALS AB Backgrounds: Sleep and circadian rhythm disruptions are prominent, trait-like features of bipolar disorder (BD) which precede the onset of mood episodes. Neurocognitive impairments also characterize BD not only during acute phases of the illness but also during remission. Although the relationship between these two debilitating aspects of the illness might seem intuitive, very little is known about their relationship. We examined the association between sleep dysfunction and neurocognition in BD. Methods: In a sample of 117 BD patients (mean age =45.0 +/- 10.7; 59.0% (n=69) male), neurocognitive functioning was assessed using the MATRICS Consensus Cognitive Battery (MCCB). Sleep quality data were collected using the Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI). Partial Pearson correlations tested for a relationship between sleep and neurocognition. Path analyses were conducted to examine the hypothesized direct influence of sleep disruption on neurocognition. Results: Higher levels of sleep disruptions were associated with a more severe clinical presentation and poorer performance in social cognition, visual learning and working memory. Social cognition and working memory were directly (negatively) predicted by sleep disruptions. Limitations: The study was limited by a relatively small sample size and the lack of behavioral and biological objectives measure of activity/rest cycles. Conclusions: Our study suggests that in patients with BD, sleep disruptions have a detrimental effect on general level of psychopathology and contribute directly to impaired cognitive functioning in the domains of social cognition and working memory. More research using objective measurement of sleep should be pursued to support these data and to further investigate the causal relationship between these disabling aspects of the illness. Published by Elsevier B.V. C1 [Russo, Manuela; Mahon, Katie; Shanahan, Megan; Ramjas, Elizabeth; Solon, Carly; Purcell, Shaun M.; Burdick, Katherine E.] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. [Russo, Manuela; Mahon, Katie; Shanahan, Megan; Ramjas, Elizabeth; Solon, Carly; Purcell, Shaun M.; Burdick, Katherine E.] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA. [Burdick, Katherine E.] James J Peters VA Med Ctr Bronx, Bronx, NY USA. RP Burdick, KE (reprint author), 1 Gustave L Levy Pl Box 1230, New York, NY 10029 USA. EM Katherine.burdick@mssm.edu FU CSRD VA [I01 CX000995]; NIMH NIH HHS [R01 MH100125, R34 MH101267] NR 46 TC 1 Z9 1 U1 1 U2 35 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD NOV 15 PY 2015 VL 187 BP 156 EP 162 DI 10.1016/j.jad.2015.08.009 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CS1RL UT WOS:000361845300023 PM 26339925 ER PT J AU Baek, JH Heo, JY Fava, M Mischoulon, D Nierenberg, A Hong, JP Roh, S Jeon, HJ AF Baek, Ji Hyun Heo, Jung Yoon Fava, Maurizio Mischoulon, David Nierenberg, Andrew Hong, Jin Pyo Roh, Sungwon Jeon, Hong Jin TI Anxiety symptoms are linked to new-onset suicidal ideation after six months of follow-up in outpatients with major depressive disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Depression; anxiety; Suicide; Phone interview ID VALIDATION; BEHAVIOR; TRIAL; PHQ-9; ANTIDEPRESSANTS; QUESTIONNAIRE; HOPELESSNESS; PERSISTENCE; PREDICTORS; FLUOXETINE AB Background: Suicide risk evaluation is one of the most challenging assessments of patients with major depressive disorder (MDD). Initial risk evaluation might be insufficient in predicting emergence of suicidal ideation during the maintenance period. We aimed to elucidate factors associated with emergence or persistence of suicidal ideation 6 months after initiation of outpatient treatment in patients with MDD. Methods: A total of 300 participants with MDD defined by DSM-IV-TR criteria underwent face-to-face interview at baseline and follow-up phone interview at 6 months later. Severity of depression, suicidal ideation, and anxiety were evaluated. Results: Among participants who did not report any suicidal idea at baseline, 10.9% reported suicidal ideation during the 6-month phone interview, while 28.4% of participants who reported suicidal ideation at baseline reported suicidal ideation during the phone interview. No significant difference in remission rate of depression was observed between the groups, but subjects without suicidal ideation at baseline had a higher rate of symptom improvement at the 6-month phone interview. After controlling for age, sex, baseline severity of suicide risk and depression and lifetime history of suicide attempts, emergence of suicidal ideation was significantly associated with anxiety level at baseline (t=2.127, p=0.039) and severity of depression symptoms at 6 month (t=-3.028, p=0.004); persistence of suicidal ideation was associated with severity of depression symptoms at 6 month (t=-4.962, p < 0.001). Limitation: Follow-up evaluation was done by phone interview. Conclusion: Anxiety at baseline needs to be carefully evaluated in assessing suicide risk of patients with MDD. (C) 2015 Elsevier B.V. All rights reserved C1 [Baek, Ji Hyun; Heo, Jung Yoon; Hong, Jin Pyo; Jeon, Hong Jin] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Psychiat,Depress Ctr, Seoul, South Korea. [Jeon, Hong Jin] SAIHST, Dept Hlth Sci & Technol, Dept Clin Res Design & Evaluat, Seoul, South Korea. [Jeon, Hong Jin] SAIHST, Dept Med Device Management & Res, Seoul, South Korea. [Fava, Maurizio; Mischoulon, David; Jeon, Hong Jin] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA USA. [Baek, Ji Hyun; Nierenberg, Andrew] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA USA. [Roh, Sungwon] Seoul Natl Hosp, Seoul, South Korea. RP Jeon, HJ (reprint author), Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Psychiat,Depress Ctr, Seoul, South Korea. EM jeonhj@skku.edu FU Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology, South Korea [2011-0013064]; Samsung Biomedical Research Institute Grant (SBRI) [C-B1-311]; Samsung Medical Center Clinical Research Development Program (CRDP) [SMO1131461] FX This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology, South Korea (No. 2011-0013064, Principal Investigator: Jeon HJ). This research was also supported by the Samsung Biomedical Research Institute Grant (SBRI) (C-B1-311, Principal Investigator: Jeon HJ) and the Samsung Medical Center Clinical Research Development Program (CRDP) (Grant SMO1131461, Principal Investigator: Jeon HJ). NR 30 TC 7 Z9 8 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD NOV 15 PY 2015 VL 187 BP 183 EP 187 DI 10.1016/j.jad.2015.08.006 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA CS1RL UT WOS:000361845300027 PM 26342171 ER PT J AU Khera, AV Millar, JS Ruotolo, G Wang, MD Rader, DJ AF Khera, Amit V. Millar, John S. Ruotolo, Giacomo Wang, Ming-Dauh Rader, Daniel J. TI Potent peroxisome proliferator-activated receptor-alpha agonist treatment increases cholesterol efflux capacity in humans with the metabolic syndrome SO EUROPEAN HEART JOURNAL LA English DT Article DE Cholesterol efflux capacity; HDL-cholesterol; Lipid metabolism; PPAR-alpha AB Aims Fibrate medications weakly stimulate the nuclear receptor peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and are currently employed clinically in patients with dyslipidaemia. The potent and selective agonist of PPAR-alpha LY518674 is known to substantially increase apolipoprotein A-I (apoA-I) turnover without major impact on steady-state levels of apoA-I or high-density lipoprotein-cholesterol (HDL-C). We sought to determine whether therapy with a PPAR-alpha agonist impacts cholesterol efflux capacity, a marker of HDL function. Methods and results Cholesterol efflux capacity was measured at baseline and after 8 weeks of therapy in a randomized, placebo-controlled trial involving participants with metabolic syndrome treated with either LY518674 100 mg daily (n = 13) or placebo (n = 15). Efflux capacity assessment was quantified using a previously validated ex vivo assay that measures the ability of apolipoprotein-B depleted plasma to mobilize cholesterol from macrophages. LY518674 led to a 15.7% increase from baseline (95% CI 3.3-28.1%; P = 0.02, P vs. placebo = 0.01) in efflux capacity. The change in apoA-I production rate in the active treatment arm was strongly linked to change in cholesterol efflux capacity (r = 0.67, P = 0.01). Conclusions Potent stimulation of PPAR-a leads to accelerated turnover of apoA-I and an increase in cholesterol efflux capacity in metabolic syndrome patients despite no change in HDL-C or apoA-I levels. This finding reinforces the notion that changes in HDL-C levels may poorly predict impact on functionality and thus has implications for ongoing pharmacologic efforts to enhance apoA-I metabolism. C1 [Khera, Amit V.] Massachusetts Gen Hosp, Dept Med, Cardiol Div, Boston, MA 02114 USA. [Millar, John S.; Rader, Daniel J.] Perelman Sch Med, Dept Med, Philadelphia, PA USA. [Millar, John S.; Rader, Daniel J.] Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA USA. [Ruotolo, Giacomo; Wang, Ming-Dauh] Eli Lilly & Co, Cardiovasc Unit, Indianapolis, IN USA. RP Khera, AV (reprint author), Massachusetts Gen Hosp, Dept Med, Cardiol Div, 55 Fruit St,Yawkey 5B, Boston, MA 02114 USA. EM avkhera@mgh.harvard.edu; rader@mail.med.upenn.edu FU Eli Lilly and Company; NIH Public Health Services Research grant [M01-RR00040]; ACCF/Merck Research Fellowship in Cardiovascular Disease FX This work was supported by a grant from Eli Lilly and Company, an NIH Public Health Services Research grant (M01-RR00040 to D.J.R.), and an ACCF/Merck Research Fellowship in Cardiovascular Disease to A.V.K. NR 7 TC 9 Z9 9 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD NOV 14 PY 2015 VL 36 IS 43 BP 3020 EP 3022 DI 10.1093/eurheartj/ehv291 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CY6BO UT WOS:000366492300014 PM 26112886 ER PT J AU Padi, M Quackenbush, J AF Padi, Megha Quackenbush, John TI Integrating transcriptional and protein interaction networks to prioritize condition-specific master regulators SO BMC SYSTEMS BIOLOGY LA English DT Article DE Network modeling; Gene regulation; Regulatory networks; Protein interaction networks; Cancer ID EPITHELIAL-MESENCHYMAL TRANSITION; SACCHAROMYCES-CEREVISIAE GENOME; COLORECTAL-CANCER; HEPATOCELLULAR-CARCINOMA; HEAT-SHOCK; GENES; YEAST; METASTASIS; EXPRESSION; CELLS AB Background: Genome-wide libraries of yeast deletion strains have been used to screen for genes that drive phenotypes such as stress response. A surprising observation emerging from these studies is that the genes with the largest changes in mRNA expression during a state transition are not those that drive that transition. Here, we show that integrating gene expression data with context-independent protein interaction networks can help prioritize master regulators that drive biological phenotypes. Results: Genes essential for survival had previously been shown to exhibit high centrality in protein interaction networks. However, the set of genes that drive growth in any specific condition is highly context-dependent. We inferred regulatory networks from gene expression data and transcription factor binding motifs in Saccharomyces cerevisiae, and found that high-degree nodes in regulatory networks are enriched for transcription factors that drive the corresponding phenotypes. We then found that using a metric combining protein interaction and transcriptional networks improved the enrichment for drivers in many of the contexts we examined. We applied this principle to a dataset of gene expression in normal human fibroblasts expressing a panel of viral oncogenes. We integrated regulatory interactions inferred from this data with a database of yeast two-hybrid protein interactions and ranked 571 human transcription factors by their combined network score. The ranked list was significantly enriched in known cancer genes that could not be found by standard differential expression or enrichment analyses. Conclusions: There has been increasing recognition that network-based approaches can provide insight into critical cellular elements that help define phenotypic state. Our analysis suggests that no one network, based on a single data type, captures the full spectrum of interactions. Greater insight can instead be gained by exploring multiple independent networks and by choosing an appropriate metric on each network. Moreover we can improve our ability to rank phenotypic drivers by combining the information from individual networks. We propose that such integrative network analysis could be used to combine clinical gene expression data with interaction databases to prioritize patient-and disease-specific therapeutic targets. C1 [Padi, Megha; Quackenbush, John] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Padi, Megha] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Quackenbush, John] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Padi, M (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. EM mpadi@jimmy.harvard.edu FU NIH [K25 HG006031, R01 HL111759] FX This study was supported by NIH grant K25 HG006031 to MP and R01 HL111759 to JQ. We thank Kimberly Glass and John Platig for discussions. NR 53 TC 2 Z9 2 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1752-0509 J9 BMC SYST BIOL JI BMC Syst. Biol. PD NOV 14 PY 2015 VL 9 AR 80 DI 10.1186/s12918-015-0228-1 PG 17 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA CX4FC UT WOS:000365653400001 PM 26576632 ER PT J AU Coati, I Fassan, M Farinati, F Graham, DY Genta, RM Rugge, M AF Coati, Irene Fassan, Matteo Farinati, Fabio Graham, David Y. Genta, Robert M. Rugge, Massimo TI Autoimmune gastritis: Pathologist's viewpoint SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Autoimmune gastritis; Metaplasia; Carcinoids; Operative link for gastritis assessment staging ID CHRONIC ATROPHIC GASTRITIS; PYLORIC GLAND ADENOMA; PERNICIOUS-ANEMIA; SYDNEY SYSTEM; T-CELLS; CANCER; METAPLASIA; STOMACH; CLASSIFICATION; PREVALENCE AB Western countries are seeing a constant decline in the incidence of Helicobacter pylori-associated gastritis, coupled with a rising epidemiological and clinical impact of autoimmune gastritis. This latter gastropathy is due to autoimmune aggression targeting parietal cells through a complex interaction of auto-antibodies against the parietal cell proton pump and intrinsic factor, and sensitized T cells. Given the specific target of this aggression, autoimmune gastritis is typically restricted to the gastric corpus-fundus mucosa. In advanced cases, the oxyntic epithelia are replaced by atrophic (and metaplastic) mucosa, creating the phenotypic background in which both gastric neuroendocrine tumors and (intestinal-type) adenocarcinomas may develop. Despite improvements in our understanding of the phenotypic changes or cascades occurring in this autoimmune setting, no reliable biomarkers are available for identifying patients at higher risk of developing a gastric neoplasm. The standardization of autoimmune gastritis histology reports and classifications in diagnostic practice is a prerequisite for implementing definitive secondary prevention strategies based on multidisciplinary diagnostic approaches integrating endoscopy, serology, histology and molecular profiling. C1 [Coati, Irene; Fassan, Matteo; Rugge, Massimo] Univ Padua, Dept Med DIMED, Surg Pathol Unit, I-35121 Padua, Italy. [Farinati, Fabio] Univ Padua, Dept Surg Oncol & Gastroenterol, Gastroenterol Unit, I-35121 Padua, Italy. [Graham, David Y.] Baylor Coll Med, Dept Med, Vet Adm Hosp, Houston, TX 77030 USA. [Genta, Robert M.] Miraca Life Sci Res Inst, Irving, TX 75039 USA. [Genta, Robert M.] VA North Texas Hlth Care Syst, Dept Pathol, Dallas, TX 75390 USA. [Genta, Robert M.] VA North Texas Hlth Care Syst, Dept Med, Dallas, TX 75390 USA. [Genta, Robert M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP Fassan, M (reprint author), Univ Padua, Dept Med DIMED, Pathol, Surg Pathol Unit, Via Gabelli 61, I-35121 Padua, Italy. EM matteo.fassan@unipd.it RI Rugge, Massimo/K-7525-2016 FU Italian Association for Cancer Research (AIRC Regional grant) [6421]; Healthy Stomach Initiative (HIS) FX Supported by A grant from the Italian Association for Cancer Research (partly, AIRC Regional grant 2008 No. 6421); and published under the auspices of the Healthy Stomach Initiative (HIS) NR 60 TC 5 Z9 5 U1 2 U2 6 PU BAISHIDENG PUBLISHING GROUP INC PI PLEASANTON PA 8226 REGENCY DR, PLEASANTON, CA 94588 USA SN 1007-9327 EI 2219-2840 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD NOV 14 PY 2015 VL 21 IS 42 BP 12179 EP 12189 DI 10.3748/wjg.v21.i42.12179 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA CW5HC UT WOS:000365025300026 PM 26576102 ER PT J AU Remfry, A Abrams, H Dudzinski, DM Weiner, RB Bhatia, RS AF Remfry, Andrew Abrams, Howard Dudzinski, David M. Weiner, Rory B. Bhatia, R. Sacha TI Assessment of inpatient multimodal cardiac imaging appropriateness at large academic medical centers SO CARDIOVASCULAR ULTRASOUND LA English DT Article DE Appropriateness use criteria; transthoracic echocardiogram; Cardiac catheterization; transesophageal echocardiogram; Single-photon emission tomography myocardial perfusion imaging ID OF-CARDIOLOGY FOUNDATION; CRITERIA TASK-FORCE; CARDIOVASCULAR COMPUTED-TOMOGRAPHY; AMERICAN-HEART-ASSOCIATION; TRANSTHORACIC ECHOCARDIOGRAPHY; MAGNETIC-RESONANCE; NUCLEAR CARDIOLOGY; DIAGNOSTIC CATHETERIZATION; THORACIC SURGEONS; FAILURE SOCIETY AB Background: Responding to concerns regarding the growth of cardiac testing, the American College of Cardiology Foundation (ACCF) published Appropriate Use Criteria (AUC) for various cardiac imaging modalities. Single modality cardiac imaging appropriateness has been reported but there have been no studies assessing the appropriateness of multiple imaging modalities in an inpatient environment. Methods: A retrospective study of the appropriateness of cardiac tests ordered by the inpatient General Internal Medicine (GIM) and Cardiology services at three Canadian academic hospitals was conducted over two one-month periods. Cardiac tests characterized were transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), single-photon emission tomography myocardial perfusion imaging (SPECT), and diagnostic cardiac catheterization. Results: Overall, 553 tests were assessed, of which 99.8 % were classifiable by AUC. 91 % of all studies were categorized as appropriate, 4 % may be appropriate and 5 % were rarely appropriate. There were high rates of appropriate use of all modalities by GIM and Cardiology throughout. Significantly more appropriate diagnostic catheterizations were ordered by Cardiology than GIM (93 % vs. 82 %, p = <0.01). Cardiology ordered more appropriate studies overall (94 % vs. 88 %, p = 0.03) but there was no difference in the rate of rarely appropriate studies (3 % vs. 6 %, p = 0.23). Conclusion: The ACCF AUC captured the vast majority of clinical scenarios for multiple cardiac imaging modalities in this multi-centered study on Cardiology and GIM inpatients in the acute care setting. The rate of appropriate ordering was high across all imaging modalities. We recommend further work towards improving appropriate utilization of cardiac imaging resources focus on the out-patient setting. C1 [Remfry, Andrew; Abrams, Howard; Bhatia, R. Sacha] Univ Toronto, Sch Med, Toronto, ON M5S 1A8, Canada. [Abrams, Howard; Bhatia, R. Sacha] Toronto Gen Hosp, Peter Munk Cardiac Ctr, Univ Hlth Network, Toronto, ON M5G 2C4, Canada. [Dudzinski, David M.; Weiner, Rory B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bhatia, R. Sacha] Univ Toronto, Womens Coll Hosp, Inst Hlth Syst Solut & Virtual Care, Toronto, ON M5S 1B2, Canada. [Bhatia, R. Sacha] Univ Toronto, Inst Clin Evaluat Sci, Div Cardiol, Univ Hlth Network, Toronto, ON M5S 1B2, Canada. [Bhatia, R. Sacha] Univ Toronto, Womens Coll Hosp, Toronto, ON M5S 1B2, Canada. RP Bhatia, RS (reprint author), Univ Toronto, Sch Med, Med Sci Bldg,1 Kings Coll Circle, Toronto, ON M5S 1A8, Canada. EM sacha.r.bhatia@wchospital.ca NR 21 TC 1 Z9 1 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-7120 J9 CARDIOVASC ULTRASOUN JI Cardiovasc. Ultrasound PD NOV 14 PY 2015 VL 13 AR 44 DI 10.1186/s12947-015-0037-0 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CV9SO UT WOS:000364627100001 PM 26573578 ER PT J AU Dixit, R Kemp, C Kulich, S Seethala, R Chiosea, S Ling, SZ Ha, PK Duvvuri, U AF Dixit, Ronak Kemp, Carolyn Kulich, Scott Seethala, Raja Chiosea, Simion Ling, Shizhang Ha, Patrick K. Duvvuri, Umamaheswar TI TMEM16A/ANO1 is differentially expressed in HPV-negative versus HPV-positive head and neck squamous cell carcinoma through promoter methylation SO SCIENTIFIC REPORTS LA English DT Article ID CANCER GENOMICS; IDENTIFICATION; SCCHN AB Head and neck squamous cell carcinoma (HNSCC) has a variety of causes. Recently, the human papilloma virus (HPV) has been implicated in the rising incidence of oropharyngeal cancer and has led to variety of studies exploring the differences between HPV-positive and HPV-negative HNSCC. The calcium-activated chloride channel TMEM16A is overexpressed in a variety of cancers, including HNSCC, but whether or not it plays different roles in HPV-positive and HPV-negative HNSCC is unknown. Here, we demonstrate that TMEM16A is preferentially overexpressed in HPV-negative HNSCC and that this overexpression of TMEM16A is associated with decreased patient survival. We also show that TMEM16A expression is decreased in HPV-positive HNSCC at the DNA, RNA, and protein levels in patient samples as well as cell lines. We demonstrate that the lower levels of TMEM16A expression in HPV-positive tumors can be attributed to both a combination of copy number alteration and promoter methylation at the DNA level. Additionally, our cellular data show that HPV-negative cell lines are more dependent on TMEM16A for survival than HPV-positive cell lines. Therefore, we suspect that the down-regulation of TMEM16A in HPV-positive HNSCC makes TMEM16A a poor therapeutic target in HPV-positive HNSCC, but a potentially useful target in HPV-negative HNSCC. C1 [Dixit, Ronak; Kemp, Carolyn; Duvvuri, Umamaheswar] Univ Pittsburgh, Dept Otolaryngol, Pittsburgh, PA 15260 USA. [Kulich, Scott; Duvvuri, Umamaheswar] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Seethala, Raja; Chiosea, Simion] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. [Ling, Shizhang; Ha, Patrick K.] Johns Hopkins Univ, Sch Med, Dept Otolaryngol, Baltimore, MD 21205 USA. RP Duvvuri, U (reprint author), Univ Pittsburgh, Dept Otolaryngol, Pittsburgh, PA 15260 USA. EM duvvuriu@upmc.edu FU Department of Veterans Affairs; PNC Foundation; University of Pittsburgh; NIH CCSG [P30 CA047904] FX We would like to acknowledge Alyssa Luvison of the Department of Pathology at the University of Pittsburgh for running the FISH analysis and providing the respective images. This work was funded in part by a Career Development Award from the Department of Veterans Affairs, the PNC Foundation, and the Competitive Medical Research Fund from the University of Pittsburgh (U.D.). We acknowledge support from the NIH CCSG P30 CA047904 for Tissue Core Facilities. This work does not represent the views of US Government or the Department of Veterans Affairs. NR 19 TC 3 Z9 3 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD NOV 13 PY 2015 VL 5 AR 16657 DI 10.1038/srep16657 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW0AU UT WOS:000364652100001 PM 26563938 ER PT J AU Wood, LB Winslow, AR Proctor, EA McGuone, D Mordes, DA Frosch, MP Hyman, BT Lauffenburger, DA Haigis, KM AF Wood, Levi B. Winslow, Ashley R. Proctor, Elizabeth A. McGuone, Declan Mordes, Daniel A. Frosch, Matthew P. Hyman, Bradley T. Lauffenburger, Douglas A. Haigis, Kevin M. TI Identification of neurotoxic cytokines by profiling Alzheimer's disease tissues and neuron culture viability screening SO SCIENTIFIC REPORTS LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; NITRIC-OXIDE; NEUROPATHOLOGIC ASSESSMENT; CEREBRAL-ISCHEMIA; INDUCED APOPTOSIS; INTERFERON-GAMMA; IN-VIVO; VEGF; ASTROCYTES; BRAIN AB Alzheimer's disease (AD) therapeutics based on the amyloid hypothesis have shown minimal efficacy in patients, suggesting that the activity of amyloid beta (A beta) represents only one aspect of AD pathogenesis. Since neuroinflammation is thought to play an important role in AD, we hypothesized that cytokines may play a direct role in promoting neuronal death. Here, we profiled cytokine expression in a small cohort of human AD and control brain tissues. We identified AD-associated cytokines using partial least squares regression to correlate cytokine expression with quantified pathologic disease state and then used neuron cultures to test whether cytokines up-regulated in AD tissues could affect neuronal viability. This analysis identified cytokines that were associated with the pathological severity. Of the top correlates, only TNF-alpha reduced viability in neuron culture when applied alone. VEGF also reduced viability when applied together with A beta, which was surprising because VEGF has been viewed as a neuro-protective protein. We found that this synthetic pro-death effect of VEGF in the context of A beta was commensurate with VEGFR-dependent changes in multiple signaling pathways that govern cell fate. Our findings suggest that profiling of tissues combined with a culture-based screening approach can successfully identify new mechanisms driving neuronal death. C1 [Wood, Levi B.; Proctor, Elizabeth A.; Haigis, Kevin M.] Harvard Univ, Sch Med, Canc Res Inst, Beth Israel Deaconess Canc Ctr, Boston, MA 02215 USA. [Wood, Levi B.; Proctor, Elizabeth A.; Haigis, Kevin M.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. [Winslow, Ashley R.; Frosch, Matthew P.; Hyman, Bradley T.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Winslow, Ashley R.; Frosch, Matthew P.; Hyman, Bradley T.] Mass Gen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. [Proctor, Elizabeth A.; Lauffenburger, Douglas A.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [McGuone, Declan; Mordes, Daniel A.; Frosch, Matthew P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Charlestown, MA 02129 USA. [McGuone, Declan; Mordes, Daniel A.; Frosch, Matthew P.] Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA. [McGuone, Declan; Mordes, Daniel A.; Frosch, Matthew P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. [McGuone, Declan; Mordes, Daniel A.; Frosch, Matthew P.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Haigis, KM (reprint author), Harvard Univ, Sch Med, Canc Res Inst, Beth Israel Deaconess Canc Ctr, Boston, MA 02215 USA. EM khaigis@bidmc.harvard.edu FU National Institutes of Health (NIH) [5R01AG040530]; Institute for Collaborative Biotechnologies from the U.S. Army Research Office [W911NF-09-0001]; NIH [5P50AG005134] FX We thank Jessica Gierut for extensive comments on this work, and Samantha Dale Strasser and Peng Qiu for comments on our PLSR analysis. We also thank Sarah Phillips and Igor Bagayev for technical assistance. This work was supported by a grant from the National Institutes of Health (NIH) (5R01AG040530 to K.M.H.) and by the Institute for Collaborative Biotechnologies through grant W911NF-09-0001 from the U.S. Army Research Office. The content of the information does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred. The Massachusetts Alzheimer's Disease Research Center is supported by NIH grant 5P50AG005134. NR 56 TC 3 Z9 3 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD NOV 13 PY 2015 VL 5 AR 16622 DI 10.1038/srep16622 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CW0AO UT WOS:000364651500001 PM 26564777 ER PT J AU Lucena-Araujo, AR Kim, HT Thome, C Jacomo, RH Melo, RA Bittencourt, R Pasquini, R Pagnano, K Gloria, ABF Chauffaille, MD Athayde, M Chiattone, CS Mito, I Bendlin, R Souza, C Bortolheiro, C Coelho-Silva, JL Schrier, SL Tallman, MS Grimwade, D Ganser, A Berliner, N Ribeiro, RC Lo-Coco, F Lowenberg, B Sanz, MA Rego, EM AF Lucena-Araujo, Antonio R. Kim, Haesook T. Thome, Carolina Jacomo, Rafael H. Melo, Raul A. Bittencourt, Rosane Pasquini, Ricardo Pagnano, Katia Gloria, Ana Beatriz F. Chauffaille, Maria de Lourdes Athayde, Melina Chiattone, Carlos S. Mito, Ingrid Bendlin, Rodrigo Souza, Carmino Bortolheiro, Cristina Coelho-Silva, Juan L. Schrier, Stanley L. Tallman, Martin S. Grimwade, David Ganser, Arnold Berliner, Nancy Ribeiro, Raul C. Lo-Coco, Francesco Lowenberg, Bob Sanz, Miguel A. Rego, Eduardo M. TI High Delta Np73/TAp73 ratio is associated with poor prognosis in acute promyelocytic leukemia SO BLOOD LA English DT Article ID ANTHRACYCLINE-BASED CHEMOTHERAPY; TRANS-RETINOIC ACID; INTERNATIONAL CONSORTIUM; P73 ISOFORMS; OVARIAN-CANCER; FEEDBACK LOOP; IN-VIVO; P53; SURVIVAL; EXPRESSION AB The TP73 gene transcript is alternatively spliced and translated into the transcriptionally active (TAp73) or inactive (Delta Np73) isoforms, with opposite effects on the expression of p53 target genes and on apoptosis induction. The imbalance between Delta Np73 and TAp73 may contribute to tumorigenesis and resistance to chemotherapy in human cancers, including hematologic malignancies. In acute promyelocytic leukemia (APL), both isoforms are expressed, but their relevance in determining response to therapy and contribution to leukemogenesis remains unknown. Here, we provide the first evidence that a higher Delta Np73/TAp73 RNA expression ratio is associated with lower survival, lower disease-free survival, and higher risk of relapse in patients with APL homogeneously treated with all-trans retinoic acid and anthracycline-based chemotherapy, according to the International Consortium on Acute Promyelocytic Leukemia (IC-APL) study. Cox proportional hazards modeling showed that a high Delta Np73/TAp73 ratio was independently associated with shorter overall survival (hazard ratio, 4.47; 95% confidence interval, 1.64-12.2; P = .0035). Our data support the hypothesis that the Delta Np73/TAp73 ratio is an important determinant of clinical response in APL and may offer a therapeutic target for enhancing chemosensitivity in blast cells. C1 [Lucena-Araujo, Antonio R.; Thome, Carolina; Jacomo, Rafael H.; Rego, Eduardo M.] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Internal Med, BR-14048900 Ribeirao Preto, SP, Brazil. [Lucena-Araujo, Antonio R.; Thome, Carolina; Jacomo, Rafael H.; Rego, Eduardo M.] Univ Sao Paulo, Ctr Cell Based Therapy, BR-14048900 Ribeirao Preto, SP, Brazil. [Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Melo, Raul A.] Univ Pernambuco, Dept Internal Med, Recife, PE, Brazil. [Melo, Raul A.] Fundacao HEMOPE, Recife, PE, Brazil. [Bittencourt, Rosane; Mito, Ingrid] Univ Fed Rio Grande do Sul, Div Hematol, Porto Alegre, RS, Brazil. [Pasquini, Ricardo] Univ Fed Parana, Div Hematol, BR-80060000 Curitiba, Parana, Brazil. [Pagnano, Katia] Univ Estadual Campinas, Hematol & Hemotherapy Ctr, Campinas, SP, Brazil. [Gloria, Ana Beatriz F.; Athayde, Melina] Univ Fed Minas Gerais, Div Hematol, Belo Horizonte, MG, Brazil. [Chauffaille, Maria de Lourdes] Univ Fed Sao Paulo, Hematol & Transfus Med, Sao Paulo, Brazil. [Chiattone, Carlos S.; Bortolheiro, Cristina] Santa Casa Med Sch, Div Hematol, Sao Paulo, Brazil. [Coelho-Silva, Juan L.] Univ Fed Pernambuco, Dept Genet, Recife, PE, Brazil. [Schrier, Stanley L.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, Weill Cornell Med Coll, Leukemia Serv, New York, NY 10021 USA. [Grimwade, David] Kings Coll London, Sch Med, Dept Med & Mol Genet, London WC2R 2LS, England. [Ganser, Arnold] Hannover Med Sch, Dept Hematol, Hannover, Germany. [Berliner, Nancy] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. [Ribeiro, Raul C.] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA. [Lo-Coco, Francesco] Univ Roma Tor Vergata, Dept Biopathol, Rome, Italy. [Lo-Coco, Francesco; Lowenberg, Bob] Santa Lucia Fdn, Rome, Italy. [Lowenberg, Bob] Erasmus Univ, Med Ctr, Dept Hematol, Rotterdam, Netherlands. [Sanz, Miguel A.] Univ Valencia, Sch Med, Dept Hematol, Valencia, Spain. RP Rego, EM (reprint author), Univ Sao Paulo, Med Sch Ribeirao Preto, Av Bandeirantes, BR-14048900 Ribeirao Preto, SP, Brazil. EM edumrego@hotmail.com RI Rego, Eduardo/A-1058-2012 OI Rego, Eduardo/0000-0003-1567-4086 FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2013/08135-2]; Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNpQ) [573754/2008-0]; FAPESP [2007/55067-1] FX This work was supported by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP; grant #2013/08135-2) and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNpQ; grant #573754/2008-0). A.R.L.-A. received a fellowship from FAPESP (grant #2007/55067-1). NR 28 TC 3 Z9 3 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD NOV 12 PY 2015 VL 126 IS 20 BP 2302 EP 2306 DI 10.1182/blood-2015-01-623330 PG 5 WC Hematology SC Hematology GA CY4PU UT WOS:000366391400008 PM 26429976 ER PT J AU Bajic, G Degn, SE Thiel, S Andersen, GR AF Bajic, Goran Degn, Soren E. Thiel, Steffen Andersen, Gregers R. TI Complement activation, regulation, and molecular basis for complement-related diseases SO EMBO JOURNAL LA English DT Review DE complement; inflammation; innate immunity; proteolytic regulation; structural biology ID MANNAN-BINDING LECTIN; HUMAN-FACTOR-H; FOLLICULAR DENDRITIC CELLS; HEMOLYTIC-UREMIC SYNDROME; PATTERN-RECOGNITION MOLECULES; MEMBRANE ATTACK COMPLEX; PATHWAY C3 CONVERTASE; COLLECTIN LIVER 1; NLRP3 INFLAMMASOME ACTIVATION; SYSTEMIC-LUPUS-ERYTHEMATOSUS AB The complement system is an essential element of the innate immune response that becomes activated upon recognition of molecular patterns associated with microorganisms, abnormal host cells, and modified molecules in the extracellular environment. The resulting proteolytic cascade tags the complement activator for elimination and elicits a pro-inflammatory response leading to recruitment and activation of immune cells from both the innate and adaptive branches of the immune system. Through these activities, complement functions in the first line of defense against pathogens but also contributes significantly to the maintenance of homeostasis and prevention of autoimmunity. Activation of complement and the subsequent biological responses occur primarily in the extracellular environment. However, recent studies have demonstrated autocrine signaling by complement activation in intracellular vesicles, while the presence of a cytoplasmic receptor serves to detect complement-opsonized intracellular pathogens. Furthermore, breakthroughs in both functional and structural studies now make it possible to describe many of the intricate molecular mechanisms underlying complement activation and the subsequent downstream events, as well as its cross talk with, for example, signaling pathways, the coagulation system, and adaptive immunity. We present an integrated and updated view of complement based on structural and functional data and describe the new roles attributed to complement. Finally, we discuss how the structural and mechanistic understanding of the complement system rationalizes the genetic defects conferring uncontrolled activation or other undesirable effects of complement. C1 [Bajic, Goran; Andersen, Gregers R.] Aarhus Univ, Dept Mol Biol & Genet, Aarhus, Denmark. [Degn, Soren E.; Thiel, Steffen] Aarhus Univ, Dept Biomed, Aarhus, Denmark. [Degn, Soren E.] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. RP Thiel, S (reprint author), Aarhus Univ, Dept Mol Biol & Genet, Aarhus, Denmark. EM st@biomed.au.dk; gra@mbg.au.dk OI Bajic, Goran/0000-0003-0480-4324 FU Danish Science Research Council (GRA); Danish Council for Independent Research, Medical Sciences; Novo-Nordisk Foundation; Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme; LUNA Nanomedicine Center; Lundbeck Foundation FX This work was supported by the LUNA Nanomedicine Center, The Lundbeck Foundation (GRA and ST), the Danish Science Research Council (GRA), and the Danish Council for Independent Research, Medical Sciences (ST). GRA received a Hallas-Moller stipend from the Novo-Nordisk Foundation. SD was supported by a Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme. NR 228 TC 26 Z9 27 U1 11 U2 32 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD NOV 12 PY 2015 VL 34 IS 22 BP 2735 EP 2757 DI 10.15252/embj.201591881 PG 23 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CY7QR UT WOS:000366604300006 PM 26489954 ER PT J AU Fogel, AR Rosenberg, JC Lehmans, FM Kuperberg, GR Patel, AD AF Fogel, Allison R. Rosenberg, Jason C. Lehmans, Frank M. Kuperberg, Gina R. Patel, Aniruddh D. TI Studying Musical and Linguistic Prediction in Comparable Ways: The Melodic Cloze Probability Method SO FRONTIERS IN PSYCHOLOGY LA English DT Article DE music; language; prediction; music cognition; melodic expectation; doze probability ID IMPLICATION-REALIZATION MODEL; LANGUAGE COMPREHENSION; BRAIN POTENTIALS; NEURAL RESPONSES; EXPECTATION; SYNTAX; INTEGRATION; ERP; INFORMATION; COMPLETION AB Prediction or expectancy is thought to play an important role in both music and language processing. However, prediction is currently studied independently in the two domains, limiting research on relations between predictive mechanisms in music and language. One limitation is a difference in how expectancy is quantified. In language, expectancy is typically measured using the close probability task, in which listeners are asked to complete a sentence fragment with the first word that comes to mind. In contrast, previous production-based studies of melodic expectancy have asked participants to sing continuations following only one to two notes. We have developed a melodic close probability task in which listeners are presented with the beginning of a novel tonal melody (5-9 notes) and are asked to sing the note they expect to come next. Half of the melodies had an underlying harmonic structure designed to constrain expectations for the next note, based on an implied authentic cadence (AC) within the melody. Each such 'authentic cadence' melody was matched to a 'non-cadential' (NC) melody matched in terms of length, rhythm and melodic contour, but differing in implied harmonic structure. Participants showed much greater consistency in the notes sung following AC vs. NC melodies on average. However, significant variation in degree of consistency was observed within both AC and NC melodies. Analysis of individual melodies suggests that pitch prediction in tonal melodies depends on the interplay of local factors just prior to the target note (e.g., local pitch interval patterns) and larger-scale structural relationships (e.g., melodic patterns and implied harmonic structure). We illustrate how the melodic close method can be used to test a computational model of melodic expectation. Future uses for the method include exploring the interplay of different factors shaping melodic expectation, and designing experiments that compare the cognitive mechanisms of prediction in music and language. C1 [Fogel, Allison R.; Kuperberg, Gina R.; Patel, Aniruddh D.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Rosenberg, Jason C.] Yale NUS Coll, Dept Arts & Humanities, Singapore, Singapore. [Lehmans, Frank M.] Tufts Univ, Dept Mus, Medford, MA 02155 USA. [Kuperberg, Gina R.] MGH HST Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Kuperberg, Gina R.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. RP Fogel, AR (reprint author), Tufts Univ, Dept Psychol, Medford, MA 02155 USA. EM allison.fogel@tufts.edu FU NICHD NIH HHS [R01 HD082527] NR 78 TC 0 Z9 0 U1 2 U2 9 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-1078 J9 FRONT PSYCHOL JI Front. Psychol. PD NOV 12 PY 2015 VL 6 AR 1718 DI 10.3389/fpsyg.2015.01718 PG 14 WC Psychology, Multidisciplinary SC Psychology GA CW7ZA UT WOS:000365216800001 PM 26617548 ER PT J AU Canver, MC Smith, EC Sher, F Pinello, L Sanjana, NE Shalem, O Chen, DD Schupp, PG Vinjamur, DS Garcia, SP Luc, S Kurita, R Nakamura, Y Fujiwara, Y Maeda, T Yuan, GC Zhang, F Orkin, SH Bauer, DE AF Canver, Matthew C. Smith, Elenoe C. Sher, Falak Pinello, Luca Sanjana, Neville E. Shalem, Ophir Chen, Diane D. Schupp, Patrick G. Vinjamur, Divya S. Garcia, Sara P. Luc, Sidinh Kurita, Ryo Nakamura, Yukio Fujiwara, Yuko Maeda, Takahiro Yuan, Guo-Cheng Zhang, Feng Orkin, Stuart H. Bauer, Daniel E. TI BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis SO NATURE LA English DT Article ID BETA-GLOBIN GENE; HUMAN CELL-TYPES; HISTONE MODIFICATIONS; TRANSCRIPTION FACTORS; LYMPHOID DEVELOPMENT; REGULATORY DNA; GENOME; CAS9; EXPRESSION; DISEASE AB Enhancers, critical determinants of cellular identity, are commonly recognized by correlative chromatin marks and gain-of-function potential, although only loss-of-function studies can demonstrate their requirement in the native genomic context. Previously, we identified an erythroid enhancer of human BCL11A, subject to common genetic variation associated with the fetal haemoglobin level, the mouse orthologue of which is necessary for eiythroid BCL11A expression. Here we develop pooled clustered regularly interspaced paiindromic repeat (CRISPR)-Cas9 guide RNA libraries to perform in situ saturating mutagenesis of the human and mouse enhancers. This approach reveals critical minimal features and discrete vulnerabilities of these enhancers. Despite conserved function of the composite enhancers, their architecture diverges. The crucial human sequences appear to be primate-specific. Through editing of primary human progenitors and mouse transgenesis, we validate the BCL11A erythroid enhancer as a target for fetal haemoglobin reinduction. The detailed enhancer map will inform therapeutic genome editing, and the screening approach described here is generally applicable to functional interrogation of non-coding genomic elements C1 [Canver, Matthew C.; Smith, Elenoe C.; Sher, Falak; Chen, Diane D.; Schupp, Patrick G.; Vinjamur, Divya S.; Luc, Sidinh; Fujiwara, Yuko; Orkin, Stuart H.; Bauer, Daniel E.] Harvard Univ, Boston Childrens Hosp, Dana Farber Canc Inst,Div Hematol Oncol,Med Sch, Harvard Stem Cell Inst,Dept Pediat,Dept Pediat On, Boston, MA 02115 USA. [Pinello, Luca; Garcia, Sara P.; Yuan, Guo-Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Pinello, Luca; Garcia, Sara P.; Yuan, Guo-Cheng] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Sanjana, Neville E.; Shalem, Ophir; Zhang, Feng] MIT, Broad Inst MIT & Harvard, McGovern Inst Brain Res, Dept Brain & Cognit Sci, Cambridge, MA 02142 USA. [Sanjana, Neville E.; Shalem, Ophir; Zhang, Feng] MIT, Dept Biol Engn, Cambridge, MA 02142 USA. [Kurita, Ryo; Nakamura, Yukio] RIKEN BioResource Ctr, Cell Engn Div, Tsukuba, Ibaraki 3050074, Japan. [Nakamura, Yukio] Univ Tsukuba, Comprehens Human Sci, Tsukuba, Ibaraki 3058577, Japan. [Fujiwara, Yuko; Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Maeda, Takahiro] Harvard Univ, Brigham & Womens Hosp, Dept Med, Div Hematol,Med Sch, Boston, MA 02115 USA. RP Bauer, DE (reprint author), Harvard Univ, Boston Childrens Hosp, Dana Farber Canc Inst,Div Hematol Oncol,Med Sch, Harvard Stem Cell Inst,Dept Pediat,Dept Pediat On, Boston, MA 02115 USA. EM zhang@broadinstitute.org; stuart_orkin@dfci.harvard.edu; daniel.bauer@childrens.harvard.edu RI Nakamura, Yukio/A-5263-2016; OI Sanjana, Neville/0000-0002-1504-0027 FU Jane Coffin Childs Memorial Fund for Medical Research Fellowship; NHGRI Career Development Award [K99HG008399]; Simons Center for the Social Brain Postdoctoral Fellowship; NIH NHGRI [K99-HG008171]; Klarman Family Foundation; Leukemia & Lymphoma Society Fellow Award; NIH [R01 A1084905, R01HL119099, R01HG005085]; NIMH [5DP1-MH100706]; NIDDK [5R01-DK097768]; Waterman award from the National Science Foundation; Keck Foundation; McKnight Foundation; Damon Runyon Foundation; Searle Scholars Foundation; Merkin Foundation; Vallee Foundation; Simons Foundation; Bob Metcalfe; Center of Excellence in Molecular Hematology [P01HL032262, P30DK049216]; NIDDK Career Development Award [K08DK093705]; Doris Duke Charitable Foundation Innovations in Clinical Research Award [2013137]; Charles H. Hood Foundation Child Health Research Award; [F30DK103359-01A1] FX We thank J. Hughes and D. Higgs for assistance with analysis of ChIP-seq; R. Mathieu and the Boston Children's Hospital Hematology/Oncology-HSCI Flow Cytometry Research Facility for cell sorting; Z. Herbert and F. Abderazzaq at the Dana-Farber Cancer Institute Molecular Biology Core Facility and Center for Cancer Computational Biology, respectively, for sequencing; J. Doench for providing TALENs; C. Peng for advice with MEL reporter cell generation; F. Godinho and M. Nguyen for technical help with ESCs and transgenic mice; A. Dass, C. Lin and S. Kamran for general technical assistance; C. Brendel and D. Williams for input regarding lentiviral transduction of HSPCs; J. Desimini for graphical assistance; and J. Xu and G. Lettre for insightful discussions. M.C.C. is supported by F30DK103359-01A1. E.C.S. is supported by a Jane Coffin Childs Memorial Fund for Medical Research Fellowship. L.P. is supported by NHGRI Career Development Award K99HG008399. N.E.S. is supported by a Simons Center for the Social Brain Postdoctoral Fellowship and NIH NHGRI award K99-HG008171. O.S. is supported by a fellowship from the Klarman Family Foundation. S.L. is supported by a Leukemia & Lymphoma Society Fellow Award. T.M. is supported by NIH R01 A1084905. G.-C.Y. is supported by NIH R01HL119099 and R01HG005085. F.Z. is supported by the NIMH (5DP1-MH100706) and NIDDK (5R01-DK097768), a Waterman award from the National Science Foundation, the Keck, McKnight, Damon Runyon, Searle Scholars, Merkin, Vallee, and Simons Foundations, and Bob Metcalfe. S.H.O. is supported by P01HL032262 and P30DK049216 (Center of Excellence in Molecular Hematology). D.E.B. is supported by an NIDDK Career Development Award K08DK093705, Doris Duke Charitable Foundation Innovations in Clinical Research Award (2013137), and Charles H. Hood Foundation Child Health Research Award. Computational tools and instructions for designing CRISPR-Cas9 sgRNA libraries for conducting non-coding screening can be found at the Zhang laboratory website http://www.genome-engineering.org. NR 60 TC 86 Z9 88 U1 10 U2 54 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD NOV 12 PY 2015 VL 527 IS 7577 BP 192 EP + DI 10.1038/nature15521 PG 23 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CV6RC UT WOS:000364396700036 PM 26375006 ER PT J AU Hayek, SS Sever, S Ko, YA Trachtman, H Awad, M Wadhwani, S Altintas, MM Wei, CL Hotton, AL French, AL Sperling, LS Lerakis, S Quyyumi, AA Reiser, J AF Hayek, Salim S. Sever, Sanja Ko, Yi-An Trachtman, Howard Awad, Mosaab Wadhwani, Shikha Altintas, Mehmet M. Wei, Changli Hotton, Anna L. French, Audrey L. Sperling, Laurence S. Lerakis, Stamatios Quyyumi, Arshed A. Reiser, Jochen TI Soluble Urokinase Receptor and Chronic Kidney Disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PLASMINOGEN-ACTIVATOR RECEPTOR; CARDIOVASCULAR RISK PREDICTION; GLOMERULAR-DISEASE; GENERAL-POPULATION; CANCER; SUPAR; EXPRESSION; PREVENTION; BIOMARKERS; HIV AB BACKGROUND Relatively high plasma levels of soluble urokinase-type plasminogen activator receptor (suPAR) have been associated with focal segmental glomerulosclerosis and poor clinical outcomes in patients with various conditions. It is unknown whether elevated suPAR levels in patients with normal kidney function are associated with future decline in the estimated glomerular filtration rate (eGFR) and with incident chronic kidney disease. METHODS We measured plasma suPAR levels in 3683 persons enrolled in the Emory Cardiovascular Biobank (mean age, 63 years; 65% men; median suPAR level, 3040 pg per milliliter) and determined renal function at enrollment and at subsequent visits in 2292 persons. The relationship between suPAR levels and the eGFR at baseline, the change in the eGFR over time, and the development of chronic kidney disease (eGFR <60 ml per minute per 1.73 m(2) of body-surface area) were analyzed with the use of linear mixed models and Cox regression after adjustment for demographic and clinical variables. RESULTS A higher suPAR level at baseline was associated with a greater decline in the eGFR during follow-up; the annual change in the eGFR was -0.9 ml per minute per 1.73 m(2) among participants in the lowest quartile of suPAR levels as compared with -4.2 ml per minute per 1.73 m(2) among participants in the highest quartile (P<0.001). The 921 participants with a normal eGFR (>= 90 ml per minute per 1.73 m(2)) at baseline had the largest suPAR-related decline in the eGFR. In 1335 participants with a baseline eGFR of at least 60 ml per minute per 1.73 m(2), the risk of progression to chronic kidney disease in the highest quartile of suPAR levels was 3.13 times as high (95% confidence interval, 2.11 to 4.65) as that in the lowest quartile. CONCLUSIONS An elevated level of suPAR was independently associated with incident chronic kidney disease and an accelerated decline in the eGFR in the groups studied. (Funded by the Abraham J. and Phyllis Katz Foundation and others.) C1 [Hayek, Salim S.; Ko, Yi-An; Awad, Mosaab; Sperling, Laurence S.; Lerakis, Stamatios; Quyyumi, Arshed A.] Emory Univ, Sch Med, Emory Clin Cardiovasc Res Inst, Div Cardiol, Atlanta, GA 30322 USA. [Ko, Yi-An] Emory Univ, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA. [Sever, Sanja] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Sever, Sanja] Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA USA. [Trachtman, Howard] NYU, Dept Pediat, Langone Med Ctr, New York, NY 10016 USA. [Wadhwani, Shikha; Altintas, Mehmet M.; Wei, Changli; French, Audrey L.; Reiser, Jochen] Rush Univ, Med Ctr, Dept Med, Chicago, IL 60612 USA. [Hotton, Anna L.; French, Audrey L.] CORE Ctr Cook Cty, Womens Interagency HIV Study, Chicago, IL USA. RP Reiser, J (reprint author), Rush Univ, Med Ctr, Kellogg Bldg,Suite 1003, Chicago, IL 60612 USA. EM aquyyum@emory.edu; jochen_reiser@rush.edu OI Trachtman, Howard/0000-0001-7447-9489; Altintas, Mehmet/0000-0002-1871-6985 FU Abraham J. and Phyllis Katz Foundation FX Funded by the Abraham J. and Phyllis Katz Foundation and others. NR 38 TC 29 Z9 30 U1 1 U2 6 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 12 PY 2015 VL 373 IS 20 BP 1916 EP 1925 DI 10.1056/NEJMoa1506362 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CV7IL UT WOS:000364445500006 PM 26539835 ER PT J AU Hazar, DB Eneanya, ND Kilcoyne, A Rosales, IA AF Hazar, D. Bora Eneanya, Nwamaka D. Kilcoyne, Aoife Rosales, Ivy A. TI Case 35-2015: A 72-Year-Old Woman with Proteinuria and a Kidney Mass SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RENAL-CELL-CARCINOMA; IDIOPATHIC MEMBRANOUS NEPHROPATHY; FOCAL SEGMENTAL GLOMERULOSCLEROSIS; NEPHROTIC SYNDROME; GLOMERULAR-DISEASES; GLOMERULONEPHRITIS; RECEPTOR; ANTIBODIES; RITUXIMAB; FAILURE C1 [Hazar, D. Bora; Eneanya, Nwamaka D.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Kilcoyne, Aoife] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Rosales, Ivy A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hazar, D. Bora] Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. [Eneanya, Nwamaka D.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Kilcoyne, Aoife] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Rosales, Ivy A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hazar, DB (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 34 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 12 PY 2015 VL 373 IS 20 BP 1959 EP 1968 DI 10.1056/NEJMcpc1505527 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CV7IL UT WOS:000364445500012 ER PT J AU Chen, YB AF Chen, Yi-Bin TI Case 23-2015: A Woman with Headache, Cognitive Impairment, and Weakness Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Chen, YB (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 12 PY 2015 VL 373 IS 20 BP 1983 EP 1983 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA CV7IL UT WOS:000364445500030 PM 26559590 ER PT J AU Hsu, JJ Finkelstein, DM Schoenfeld, DA AF Hsu, Jessie J. Finkelstein, Dianne M. Schoenfeld, David A. TI Outcome-Driven Cluster Analysis with Application to Microarray Data SO PLOS ONE LA English DT Article ID GENE-EXPRESSION PROFILES; REGRESSION SHRINKAGE; VARIABLE SELECTION; MODEL AB One goal of cluster analysis is to sort characteristics into groups (clusters) so that those in the same group are more highly correlated to each other than they are to those in other groups. An example is the search for groups of genes whose expression of RNA is correlated in a population of patients. These genes would be of greater interest if their common level of RNA expression were additionally predictive of the clinical outcome. This issue arose in the context of a study of trauma patients on whom RNA samples were available. The question of interest was whether there were groups of genes that were behaving similarly, and whether each gene in the cluster would have a similar effect on who would recover. For this, we develop an algorithm to simultaneously assign characteristics (genes) into groups of highly correlated genes that have the same effect on the outcome (recovery). We propose a random effects model where the genes within each group (cluster) equal the sum of a random effect, specific to the observation and cluster, and an independent error term. The outcome variable is a linear combination of the random effects of each cluster. To fit the model, we implement a Markov chain Monte Carlo algorithm based on the likelihood of the observed data. We evaluate the effect of including outcome in the model through simulation studies and describe a strategy for prediction. These methods are applied to trauma data from the Inflammation and Host Response to Injury research program, revealing a clustering of the genes that are informed by the recovery outcome. C1 [Hsu, Jessie J.; Finkelstein, Dianne M.; Schoenfeld, David A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Hsu, Jessie J.; Finkelstein, Dianne M.; Schoenfeld, David A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Hsu, Jessie J.] Genentech Inc, San Francisco, CA 94080 USA. RP Finkelstein, DM (reprint author), Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. EM dfinkelstein@mgh.harvard.edu FU National Institute of General Medical Sciences [T32GM074897, 2-U54-GM062119] FX This work was supported by the Joint Interdisciplinary Training Program in 376 Biostatistics and Computational Biology (T32GM074897) and Inflammation and the 377 Host Response to Injury Large-Scale Collaborative Project (2-U54-GM062119) from the 378 National Institute of General Medical Sciences. NR 20 TC 0 Z9 0 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 12 PY 2015 VL 10 IS 11 AR e0141874 DI 10.1371/journal.pone.0141874 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CV7UL UT WOS:000364480900006 PM 26562156 ER PT J AU Bujakowska, KM White, J Place, E Consugar, M Comander, J AF Bujakowska, Kinga M. White, Joseph Place, Emily Consugar, Mark Comander, Jason TI Efficient In Silico Identification of a Common Insertion in the MAK Gene which Causes Retinitis Pigmentosa SO PLOS ONE LA English DT Article ID GENERATION; MUTATIONS; DIVERSITY; VARIANTS; IDENTIFY; DISEASES; ELEMENTS; READS AB Background Next generation sequencing (NGS) offers a rapid and comprehensive method of screening for mutations associated with retinitis pigmentosa and related disorders. However, certain sequence alterations such as large insertions or deletions may remain undetected using standard NGS pipelines. One such mutation is a recently-identified Alu insertion into the Male Germ Cell-Associated Kinase (MAK) gene, which is missed by standard NGS-based variant callers. Here, we developed an in silico method of searching NGS raw sequence reads to detect this mutation, without the need to recalculate sequence alignments or to screen every sample by PCR. Methods The Linux program grep was used to search for a 23 bp "probe" sequence containing the known junction sequence of the insert. A corresponding search was performed with the wildtype sequence. The matching reads were counted and further compared to the known sequences of the full wildtype and mutant genomic loci. (See https://github.com/MEEIBioinformaticsCenter/grepsearch.) Results In a test sample set consisting of eleven previously published homozygous mutants, detection of the MAK-Alu insertion was validated with 100% sensitivity and specificity. As a discovery cohort, raw NGS reads from 1,847 samples (including custom and whole exome selective capture) were searched in similar to 1 hour on a local computer cluster, yielding an additional five samples with MAK-Alu insertions and solving two previously unsolved pedigrees. Of these, one patient was homozygous for the insertion, one compound heterozygous with a missense change on the other allele (c. 46G>A; p. Gly16Arg), and three were heterozygous carriers. Conclusions Using the MAK-Alu grep program proved to be a rapid and effective method of finding a known, disease-causing Alu insertion in a large cohort of patients with NGS data. This simple approach avoids wet-lab assays or computationally expensive algorithms, and could also be used for other known disease-causing insertions and deletions. C1 [Bujakowska, Kinga M.; White, Joseph; Place, Emily; Consugar, Mark; Comander, Jason] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Genom Inst, Boston, MA 02115 USA. RP Comander, J (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Genom Inst, Boston, MA 02115 USA. EM Jason_comander@meei.harvard.edu FU Fleming Family Foundation; NEI [K12 EY016335]; Research to Prevent Blindness FX KMB was supported by a fellowship with the Fleming Family Foundation. JC was supported by NEI K12 EY016335 and a Career Development Award from Research to Prevent Blindness. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 30 TC 0 Z9 0 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 11 PY 2015 VL 10 IS 11 AR e0142614 DI 10.1371/journal.pone.0142614 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CV7DR UT WOS:000364433100101 PM 26558903 ER PT J AU Butt, AA Yan, P Simon, TG Chung, RT Abou-Samra, AB AF Butt, Adeel A. Yan, Peng Simon, Tracey G. Chung, Raymond T. Abou-Samra, Abdul-Badi CA ERCHIVES Study Team TI Changes in circulating lipids level over time after acquiring HCV infection: results from ERCHIVES SO BMC INFECTIOUS DISEASES LA English DT Article DE HCV; Lipid; Cholesterol; LDL; ERCHIVES; Seroconversion ID HEPATITIS-C VIRUS; INSULIN-RESISTANCE; GENOTYPE 3; VETERANS; SURVIVAL; RISK; TRIGLYCERIDE; PREDICTORS; PROTEIN; ANEMIA AB Background: Changes in lipid levels over time after acquiring HCV infection, and how they differ from HCV-uninfected persons are unknown. Methods: We used ERCHIVES to identify those with a known HCV seroconversion window and persistently negative controls. We excluded subjects with HIV and hepatitis B and those who received lipid lowering agents. Total Cholesterol (TC), low-density lipoproteins (LDL), high-density lipoproteins (HDL), triglycerides (TG) and non-HDL cholesterol were retrieved at yearly intervals and plotted over time. Results: Among 1,270 HCV+ and 5,070 HCV-subjects, median age [IQR] was 47[37,53] for HCV+ and 52[47,57] for the HCV-group; 69 % were White and 91 % were males in each group. Mean BMI [SD] was 26.94[6.73] in the HCV+ and 28.15 [5.98] in the HCV-group (P < 0.001). Over a 10-year follow-up period among HCV+ persons, TC decreased by (mean (SD) mg/dL) 12.06(36.95), LDL by 9.22(31.44), TG by 13.58(87.01) and non-HDL-C by 12.55(35.14). Among HCV-persons, TC cholesterol decreased by 4.15(31.21), LDL by 4.16(26.51); TG by 4.42(82.34) and non-HDL-C by 5.78(30.17). Conclusions: After HCV acquisition, TC, LDL, TG and non-HDL-C progressively decline over time independent of BMI and liver fibrosis. Consequences of lipid changes and the need and optimal timing of lipid lowering therapy in HCV+ persons require further study. C1 [Butt, Adeel A.; Yan, Peng] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15213 USA. [Butt, Adeel A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Butt, Adeel A.] Hamad Healthcare Qual Inst, Doha, Qatar. [Butt, Adeel A.; Abou-Samra, Abdul-Badi] Hamad Med Corp, Doha, Qatar. [Simon, Tracey G.; Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Butt, AA (reprint author), VA Pittsburgh Healthcare Syst, 3601 Fifth Ave,Suite 3A, Pittsburgh, PA 15213 USA. EM aabutt@pitt.edu FU Gilead Sciences; AbbVie FX AAB: grants to the institution by Gilead Sciences and AbbVie. PY, TGS, RTC and ABA report no conflict of interest. NR 33 TC 3 Z9 3 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2334 J9 BMC INFECT DIS JI BMC Infect. Dis. PD NOV 11 PY 2015 VL 15 AR 510 DI 10.1186/s12879-015-1268-2 PG 9 WC Infectious Diseases SC Infectious Diseases GA CW8YY UT WOS:000365286600001 PM 26558512 ER PT J AU Jarosiewicz, B Sarma, AA Bacher, D Masse, NY Simeral, JD Sorice, B Oakley, EM Blabe, C Pandarinath, C Gilja, V Cash, SS Eskandar, EN Friehs, G Henderson, JM Shenoy, KV Donoghue, JP Hochberg, LR AF Jarosiewicz, Beata Sarma, Anish A. Bacher, Daniel Masse, Nicolas Y. Simeral, John D. Sorice, Brittany Oakley, Erin M. Blabe, Christine Pandarinath, Chethan Gilja, Vikash Cash, Sydney S. Eskandar, Emad N. Friehs, Gerhard Henderson, Jaimie M. Shenoy, Krishna V. Donoghue, John P. Hochberg, Leigh R. TI Virtual typing by people with tetraplegia using a self-calibrating intracortical brain-computer interface SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID PERFORMANCE NEURAL PROSTHESIS; CORTICAL CONTROL; MOVEMENT; HUMANS; ARM; RECORDINGS; ALGORITHM; MUSCLES; DEVICES; SYSTEM AB Brain-computer interfaces (BCIs) promise to restore independence for people with severe motor disabilities by translating decoded neural activity directly into the control of a computer. However, recorded neural signals are not stationary (that is, can change over time), degrading the quality of decoding. Requiring users to pause what they are doing whenever signals change to perform decoder recalibration routines is time-consuming and impractical for everyday use of BCIs. We demonstrate that signal nonstationarity in an intracortical BCI can be mitigated automatically in software, enabling long periods (hours to days) of self-paced point-and-click typing by people with tetraplegia, without degradation in neural control. Three key innovations were included in our approach: tracking the statistics of the neural activity during self-timed pauses in neural control, velocity bias correction during neural control, and periodically recalibrating the decoder using data acquired during typing by mapping neural activity to movement intentions that are inferred retrospectively based on the user's self-selected targets. These methods, which can be extended to a variety of neurally controlled applications, advance the potential for intracortical BCIs to help restore independent communication and assistive device control for people with paralysis. C1 [Jarosiewicz, Beata; Masse, Nicolas Y.; Donoghue, John P.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Jarosiewicz, Beata; Sarma, Anish A.; Simeral, John D.; Donoghue, John P.; Hochberg, Leigh R.] Dept Vet Affairs Med Ctr, Ctr Neurorestorat & Neurotechnol, Rehabil R&D Serv, Providence, RI 02908 USA. [Jarosiewicz, Beata; Sarma, Anish A.; Bacher, Daniel; Masse, Nicolas Y.; Simeral, John D.; Donoghue, John P.; Hochberg, Leigh R.] Brown Univ, Brown Inst Brain Sci, Providence, RI 02912 USA. [Sarma, Anish A.; Bacher, Daniel; Simeral, John D.; Gilja, Vikash; Donoghue, John P.; Hochberg, Leigh R.] Brown Univ, Sch Engn, Providence, RI 02912 USA. [Simeral, John D.; Sorice, Brittany; Oakley, Erin M.; Cash, Sydney S.; Hochberg, Leigh R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Blabe, Christine; Pandarinath, Chethan; Gilja, Vikash; Henderson, Jaimie M.] Stanford Univ, Dept Neurosurg, Stanford, CA 94305 USA. [Pandarinath, Chethan; Henderson, Jaimie M.; Shenoy, Krishna V.] Stanford Univ, Stanford Neurosci Inst, Stanford, CA 94305 USA. [Pandarinath, Chethan; Gilja, Vikash; Shenoy, Krishna V.] Stanford Univ, Dept Elect Engn, Stanford, CA 94305 USA. [Cash, Sydney S.; Hochberg, Leigh R.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Eskandar, Emad N.] Harvard Univ, Sch Med, Neurosurg, Boston, MA 02115 USA. [Eskandar, Emad N.] Massachusetts Gen Hosp, Boston, MA 02115 USA. [Friehs, Gerhard] Rhode Isl Hosp, Neurosurg, Providence, RI 02903 USA. [Shenoy, Krishna V.] Stanford Univ, Dept Neurobiol, Stanford, CA 94305 USA. [Shenoy, Krishna V.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA. [Shenoy, Krishna V.] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA. RP Jarosiewicz, B (reprint author), Brown Univ, Dept Neurosci, Providence, RI 02912 USA. EM beata@brown.edu OI Pandarinath, Chethan/0000-0003-1241-1432; Blabe, Christine/0000-0003-4623-4251 FU Office of Research and Development, Rehabilitation R&D Service, Department of Veterans Affairs [B6310W, B6453R, B6459L, A6779I]; NIH: National Institute on Deafness and Other Communication Disorders [R01DC009899, R01DC014034]; National Institute of Child Health and Human-National Center for Medical Rehabilitation Research (NICHD-NCMRR) [N01HD53403, N01HD10018]; NICHD [RC1HD063931]; National Institute of Neurological Disorders and Stroke [RO1NS066311-S1]; Doris Duke Charitable Foundation; Massachusetts General Hospital (MGH)-Deane Institute; Joseph Martin Prize for Basic Research; Katie Samson Foundation; Craig H. Neilsen Foundation; Stanford Institute for Neuro-Innovation and Translational Neuroscience; Stanford BioX-NeuroVentures; Garlick Family FX This work was supported by the following: Office of Research and Development, Rehabilitation R&D Service, Department of Veterans Affairs (B6310W, B6453R, B6459L, and A6779I); NIH: National Institute on Deafness and Other Communication Disorders (R01DC009899 and R01DC014034), National Institute of Child Health and Human-National Center for Medical Rehabilitation Research (NICHD-NCMRR) (N01HD53403 and N01HD10018), NICHD (RC1HD063931), National Institute of Neurological Disorders and Stroke (RO1NS066311-S1); Doris Duke Charitable Foundation; Massachusetts General Hospital (MGH)-Deane Institute; Joseph Martin Prize for Basic Research; Katie Samson Foundation; Craig H. Neilsen Foundation; Stanford Institute for Neuro-Innovation and Translational Neuroscience; Stanford BioX-NeuroVentures; and Garlick Family. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Department of Veterans Affairs or the U.S. government. Caution: Investigational device. Limited by Federal Law to Investigational Use. NR 54 TC 17 Z9 17 U1 2 U2 14 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 EI 1946-6242 J9 SCI TRANSL MED JI Sci. Transl. Med. PD NOV 11 PY 2015 VL 7 IS 313 AR 313ra179 DI 10.1126/scitranslmed.aac7328 PG 10 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA CW8GL UT WOS:000365237400004 PM 26560357 ER PT J AU Li, M Tao, Y Shu, YL LaRochelle, JR Steinauer, A Thompson, D Schepartz, A Chen, ZY Liu, DR AF Li, Margie Tao, Yong Shu, Yilai LaRochelle, Jonathan R. Steinauer, Angela Thompson, David Schepartz, Alanna Chen, Zheng-Yi Liu, David R. TI Discovery and Characterization of a Peptide That Enhances Endosomal Escape of Delivered Proteins in Vitro and in Vivo SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID MAMMALIAN-CELLS; ANTIMICROBIAL PEPTIDES; SUPERCHARGED PROTEINS; FUNCTIONAL PROTEINS; GENE-THERAPY; PERMEABILITY; TRANSDUCTION; THERAPEUTICS; REPLACEMENT; MECHANISMS AB The inefficient delivery of proteins into mammalian cells remains a major barrier to realizing the therapeutic potential of many proteins. We and others have previously shown that superpositively charged proteins are efficiently endocytosed and can bring associated proteins and nucleic acids into cells. The vast majority of cargo delivered in this manner, however, remains in endosomes and does not reach the cytosol. In this study we designed and implemented a screen to discover peptides that enhance the endosomal escape of proteins fused to superpositively charged GFP (+36 GFP). From a screen of peptides previously reported to disrupt microbial membranes without known mammalian cell toxicity, we discovered a 13-residue peptide, aurein 1.2, that substantially increases cytosolic protein delivery by up to similar to 5-fold in a cytosolic fractionation assay in cultured cells. Four additional independent assays for nonendosomal protein delivery collectively suggest that aurein 1.2 enhances endosomal escape of associated endocytosed protein cargo. Structure function studies clarified peptide sequence and protein conjugation requirements for endosomal escape activity. When applied to the in vivo delivery of +36 GFP-Cre recombinase fusions into the inner ear of live mice, fusion with aurein 1.2 dramatically increased nonendosomal Cre recombinase delivery potency, resulting in up to 100% recombined inner hair cells and 96% recombined outer hair cells, compared to 0-4% recombined hair cells from +36-GFP-Cre without aurein 1.2. Collectively, these findings describe a genetically encodable, endosome escape-enhancing peptide that can substantially increase the cytoplasmic delivery of cationic proteins in vitro and in vivo. C1 [Li, Margie; Thompson, David; Liu, David R.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Tao, Yong; Shu, Yilai; Chen, Zheng-Yi] Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. [Tao, Yong; Shu, Yilai; Chen, Zheng-Yi] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02114 USA. [Tao, Yong; Shu, Yilai; Chen, Zheng-Yi] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Shu, Yilai] Fudan Univ, Shanghai Med Coll, Eye Ear Nose & Throat Hosp, Dept Otol & Skull Base Survery, Shanghai 200031, Peoples R China. [Shu, Yilai] Minist Hlth, Key Lab Hearing Med, Shanghai 200031, Peoples R China. [LaRochelle, Jonathan R.; Schepartz, Alanna] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA. [Steinauer, Angela; Schepartz, Alanna] Yale Univ, Dept Chem, New Haven, CT 06520 USA. [Liu, David R.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. RP Liu, DR (reprint author), Harvard Univ, Dept Chem & Chem Biol, 12 Oxford St, Cambridge, MA 02138 USA. EM drliu@fas.harvard.edu FU Howard Hughes Medical Institute; NIH/NIGMS [R01 GM095501]; NIH/NIDCD [R01 DC006908]; Harvard CCB; Frederick and Ines Yeatts Hair Cell Regeneration grant; National Nature Science Foundation of China [NSFC81300824] FX This work was supported by the Howard Hughes Medical Institute and the NIH/NIGMS (R01 GM095501) the NIH/NIDCD (R01 DC006908). M.L. was supported by fellowships from Harvard CCB. Y.T. and Y.S were supported by the Frederick and Ines Yeatts Hair Cell Regeneration grant. Y.S. was supported by The National Nature Science Foundation of China (NSFC81300824). Angela Steinauer is a Howard Hughes Medical Institute International Student Research fellow. We are grateful to Thomas Hasaka and Nicola Tolliday of the Broad Institute for assistance with the primary screen. NR 47 TC 14 Z9 14 U1 12 U2 65 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD NOV 11 PY 2015 VL 137 IS 44 BP 14084 EP 14093 DI 10.1021/jacs.5b05694 PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA CW1CQ UT WOS:000364727600020 PM 26465072 ER PT J AU Langdon, CG Wiedemann, N Held, MA Mamillapalli, R Iyidogan, P Theodosakis, N Platt, JT Levy, F Vuagniaux, G Wang, SM Bosenberg, MW Stern, DF AF Langdon, Casey G. Wiedemann, Norbert Held, Matthew A. Mamillapalli, Ramanaiah Iyidogan, Pinar Theodosakis, Nicholas Platt, James T. Levy, Frederic Vuagniaux, Gregoire Wang, Shaomeng Bosenberg, Marcus W. Stern, David F. TI SMAC mimetic Debio 1143 synergizes with taxanes, topoisomerase inhibitors and bromodomain inhibitors to impede growth of lung adenocarcinoma cells SO ONCOTARGET LA English DT Article DE SMAC mimetic; combination therapy; lung adenocarcinoma; high throughput screening; bromodomain inhibitor ID NF-KAPPA-B; ALPHA-DEPENDENT APOPTOSIS; MEDIATED SENSITIZATION; CANCER-CELLS; THERAPEUTIC STRATEGY; MULTIPLE INHIBITOR; DRUG-COMBINATION; ACUTE-LEUKEMIA; KINASE NIK; ACTIVATION AB Targeting anti-apoptotic proteins can sensitize tumor cells to conventional chemotherapies or other targeted agents. Antagonizing the Inhibitor of Apoptosis Proteins (IAPs) with mimetics of the pro-apoptotic protein SMAC is one such approach. We used sensitization compound screening to uncover possible agents with the potential to further sensitize lung adenocarcinoma cells to the SMAC mimetic Debio 1143. Several compounds in combination with Debio 1143, including taxanes, topoisomerase inhibitors, and bromodomain inhibitors, super-additively inhibited growth and clonogenicity of lung adenocarcinoma cells. Co-treatment with Debio 1143 and the bromodomain inhibitor JQ1 suppresses the expression of c-IAP1, c-IAP2, and XIAP. Non-canonical NF-kappa B signaling is also activated following Debio 1143 treatment, and Debio 1143 induces the formation of the ripoptosome in Debio 1143-sensitive cell lines. Sensitivity to Debio 1143 and JQ1 co-treatment was associated with baseline caspase-8 expression. In vivo treatment of lung adenocarcinoma xenografts with Debio 1143 in combination with JQ1 or docetaxel reduced tumor volume more than either single agent alone. As Debio 1143-containing combinations effectively inhibited both in vitro and in vivo growth of lung adenocarcinoma cells, these data provide a rationale for Debio 1143 combinations currently being evaluated in ongoing clinical trials and suggest potential utility of other combinations identified here. C1 [Langdon, Casey G.; Held, Matthew A.; Mamillapalli, Ramanaiah; Iyidogan, Pinar; Theodosakis, Nicholas; Platt, James T.; Bosenberg, Marcus W.; Stern, David F.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. [Langdon, Casey G.; Held, Matthew A.; Mamillapalli, Ramanaiah; Iyidogan, Pinar; Theodosakis, Nicholas; Platt, James T.; Bosenberg, Marcus W.; Stern, David F.] Yale Univ, Sch Med, Yale Canc Ctr, New Haven, CT USA. [Wiedemann, Norbert; Levy, Frederic; Vuagniaux, Gregoire] Debiopharm Int SA, Lausanne, Switzerland. [Platt, James T.] Yale Canc Ctr, Breast Med Oncol Grp, New Haven, CT USA. [Bosenberg, Marcus W.] Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA. [Wang, Shaomeng] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Held, Matthew A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA USA. RP Stern, DF (reprint author), Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. EM df.stern@yale.edu FU Debiopharm International SA; NIH [T32GM007324]; US National Cancer Institute [P30 CA16359] FX This work was supported by Debiopharm International SA. CGL was supported by NIH training grant T32GM007324. Yale Center for Molecular Discovery is supported in part by US National Cancer Institute grant P30 CA16359 awarded to Yale Cancer Center. NR 50 TC 1 Z9 1 U1 0 U2 0 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD NOV 10 PY 2015 VL 6 IS 35 BP 37419 EP 37434 PG 16 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CY0RL UT WOS:000366113200036 ER PT J AU D'Souza, A Dispenzieri, A Wirk, B Zhang, MJ Huang, JX Gertz, MA Kyle, RA Kumar, S Comenzo, RL Gale, RP Lazarus, HM Savani, BN Cornell, RF Weiss, BM Vogl, DT Freytes, CO Scott, EC Landau, HJ Moreb, JS Costa, LJ Ramanathan, M Callander, NS Kamble, RT Olsson, RF Ganguly, S Nishihori, T Kindwall-Keller, TL Wood, WA Mark, TM Hari, P AF D'Souza, Anita Dispenzieri, Angela Wirk, Baldeep Zhang, Mei-Jie Huang, Jiaxing Gertz, Morie A. Kyle, Robert A. Kumar, Shaji Comenzo, Raymond L. Gale, Robert Peter Lazarus, Hillard M. Savani, Bipin N. Cornell, Robert F. Weiss, Brendan M. Vogl, Dan T. Freytes, Cesar O. Scott, Emma C. Landau, Heather J. Moreb, Jan S. Costa, Luciano J. Ramanathan, Muthalagu Callander, Natalie S. Kamble, Rammurti T. Olsson, Richard F. Ganguly, Siddhartha Nishihori, Taiga Kindwall-Keller, Tamila L. Wood, William A. Mark, Tomer M. Hari, Parameswaran TI Improved Outcomes After Autologous Hematopoietic Cell Transplantation for Light Chain Amyloidosis: A Center for International Blood and Marrow Transplant Research Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PRIMARY SYSTEMIC AMYLOIDOSIS; HIGH-DOSE MELPHALAN; AL AMYLOIDOSIS; CARDIAC BIOMARKERS; MULTIPLE-MYELOMA; STAGING SYSTEM; DEXAMETHASONE; BORTEZOMIB; SURVIVAL; CYCLOPHOSPHAMIDE AB Purpose Autologous hematopoietic cell transplantation, or autotransplantation, is effective in light-chain amyloidosis (AL), but it is associated with a high risk of early mortality (EM). In a multicenter randomized comparison against oral chemotherapy, autotransplantation was associated with 24% EM. We analyzed trends in outcomes after autologous hematopoietic cell transplantation for AL in North America. Patients and Methods Between 1995 and 2012, 1,536 patients with AL who underwent autotransplantation at 134 centers were identified in the Center for International Blood and Marrow Transplant Research database. EM and overall survival (OS) were analyzed in three time cohorts: 1995 to 2000 (n = 140), 2001 to 2006 (n = 596), and 2007 to 2012 (n = 800). Hematologic and renal responses and factors associated with EM, relapse and/or progression, progression-free survival and OS were analyzed in more recent subgroups from 2001 to 2006 (n = 197) and from 2007 to 2012 (n = 157). Results Mortality at 30 and 100 days progressively declined over successive time periods from 11% and 20%, respectively, in 1995 to 2000 to 5% and 11%, respectively, in 2001 to 2006, and to 3% and 5%, respectively, in 2007 to 2012. Correspondingly, 5-year OS improved from 55% in 1995 to 2000 to 61% in 2001 to 2006 and to 77% in 2007 to 2012. Hematologic response to transplantation improved in the latest cohort. Renal response rate was 32%. Centers performing more than four AL transplantations per year had superior survival outcomes. In the multivariable analysis, cardiac AL was associated with high EM and inferior progression-free survival and OS. Autotransplantation in 2007 to 2012 and use of higher dosages of melphalan were associated with a lowered relapse risk. A Karnofsky score less than 80 and creatinine levels 2 mg/m(2) or greater were associated with worsened OS. Conclusion Post-transplantation survival in AL has improved, with a dramatic reduction in early post-transplantation mortality and excellent 5-year survival. The risk-benefit ratio for autotransplantation has changed, and randomized comparison with nontransplantation approaches is again warranted. (C) 2015 by American Society of Clinical Oncology C1 [D'Souza, Anita; Zhang, Mei-Jie; Huang, Jiaxing; Hari, Parameswaran] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Zhang, Mei-Jie] Med Coll Wisconsin, Inst Hlth & Soc, Milwaukee, WI 53226 USA. [Callander, Natalie S.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA. [Dispenzieri, Angela; Gertz, Morie A.; Kyle, Robert A.; Kumar, Shaji] Mayo Clin, Rochester, MN USA. [Wirk, Baldeep] Seattle Canc Care Alliance, Seattle, WA USA. [Comenzo, Raymond L.] Tufts Med Ctr, Boston, MA USA. [Ramanathan, Muthalagu] Univ Massachusetts, Mem Med Ctr, Worcester, MA 01605 USA. [Gale, Robert Peter] Univ London Imperial Coll Sci Technol & Med, Hematol Res Ctr, London, England. [Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Cleveland, OH USA. [Savani, Bipin N.; Cornell, Robert F.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Weiss, Brendan M.; Vogl, Dan T.] Univ Penn, Med Ctr, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Freytes, Cesar O.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Kamble, Rammurti T.] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. [Scott, Emma C.] Oregon Hlth & Sci Univ, Knight Canc Inst, Ctr Hematol Malignancies, Portland, OR 97201 USA. [Landau, Heather J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Mark, Tomer M.] Weill Cornell Med Coll, New York, NY USA. [Moreb, Jan S.] Shands HealthCare, Gainesville, FL USA. [Moreb, Jan S.] Univ Florida, Gainesville, FL USA. [Nishihori, Taiga] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Costa, Luciano J.] Univ Alabama Birmingham, Birmingham, AL USA. [Olsson, Richard F.] Karolinska Inst, Stockholm, Sweden. [Olsson, Richard F.] Uppsala Univ, Ctr Clin Res Sormland, Uppsala, Sweden. [Ganguly, Siddhartha] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Kindwall-Keller, Tamila L.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Wood, William A.] Univ N Carolina, Chapel Hill, NC USA. RP D'Souza, A (reprint author), Med Coll Wisconsin, Dept Med, Div Hematol Oncol, 9200 W Wisconsin Ave,Ste C5500, Milwaukee, WI 53226 USA. EM andsouza@mcw.edu OI Hari, Parameswaran/0000-0002-8800-297X; Dispenzieri, Angela/0000-0001-8780-9512 FU Celgene; Millennium Pharmaceuticals; Janssen Oncology; Pfizer; Novartis; Onyx; Millennium; Sanofi Pasteur; Janssen Pharmaceuticals; Prothena; Takeda Pharmaceuticals; Jannsen Pharmaceuticals; Array BioPharma; Karyopharm; Janssen Research Development; Acetylon Pharmaceuticals; GlaxoSmithKline; Calithera Biosciences; Constellation Pharmaceuticals; Merck; Takeda; Pharmacyclics; Gilead Sciences; Sanofi; Celldex; US Biotest FX Celgene (Inst), Millennium Pharmaceuticals (Inst), Janssen Oncology (Inst), Pfizer (Inst); Celgene, Novartis, Onyx, Millennium, Sanofi Pasteur, Janssen Pharmaceuticals; Prothena, Takeda Pharmaceuticals, Jannsen Pharmaceuticals, Array BioPharma, Karyopharm; Prothena, Janssen Research & Development; Millennium Pharmaceuticals, Acetylon Pharmaceuticals, GlaxoSmithKline, Calithera Biosciences, Constellation Pharmaceuticals; Merck; Millennium Pharmaceuticals, Takeda; Onyx, Takeda; Celgene, Gilead Sciences, Millennium Pharmaceuticals, Pharmacyclics; Janssen Pharmaceuticals, Sanofi, Celgene; Celldex, US Biotest; Celgene (Inst), Onyx (Inst); Millennium Pharmaceuticals (Inst), Celgene (Inst) NR 30 TC 14 Z9 14 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 10 PY 2015 VL 33 IS 32 BP 3741 EP + DI 10.1200/JCO.2015.62.4015 PG 12 WC Oncology SC Oncology GA CX9IX UT WOS:000366020100013 PM 26371138 ER PT J AU Kim, YH Tavallaee, M Sundram, U Salva, KA Wood, GS Li, SF Rozati, S Nagpal, S Krathen, M Reddy, S Hoppe, RT Nguyen-Lin, A Weng, WK Armstrong, R Pulitzer, M Advani, RH Horwitz, SM AF Kim, Youn H. Tavallaee, Mahkam Sundram, Uma Salva, Katrin A. Wood, Gary S. Li, Shufeng Rozati, Sima Nagpal, Seema Krathen, Michael Reddy, Sunil Hoppe, Richard T. Nguyen-Lin, Annie Weng, Wen-Kai Armstrong, Randall Pulitzer, Melissa Advani, Ranjana H. Horwitz, Steven M. TI Phase II Investigator-Initiated Study of Brentuximab Vedotin in Mycosis Fungoides and Sezary Syndrome With Variable CD30 Expression Level: A Multi-Institution Collaborative Project SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID STEM-CELL TRANSPLANTATION; LIGHT-CHAIN AMYLOIDOSIS; PRIMARY SYSTEMIC AMYLOIDOSIS; HIGH-DOSE MELPHALAN; AL AMYLOIDOSIS; CARDIAC BIOMARKERS; STAGING SYSTEM; DEXAMETHASONE; BORTEZOMIB; SURVIVAL AB Purpose In contrast to Hodgkin lymphoma and systemic anaplastic large-cell lymphoma, CD30 expression of malignant lymphocytes in mycosis fungoides (MF) and Szary syndrome (SS) is quite variable. Clinical activity and safety of brentuximab vedotin, a CD30 targeting antibody-drug conjugate, was evaluated in MF and SS. Tissue and blood biomarkers of clinical response were explored. Patients and Methods In this phase II study, patients with MF or SS with negligible to 100% CD30 expression levels were treated with brentuximab vedotin (1.8 mg/kg) every 3 weeks for a maximum of sixteen doses. The primary end point was overall global response rate. Secondary end points included correlation of tissue CD30 expression level with clinical response, time to response, duration of response, progression-free and event-free survivals, and safety. Results Of the 32 patients enrolled and treated, 30 patients had available efficacy evaluations. Objective global response was observed in 21 (70%) of 30 patients (90% CI, 53% to 83%). CD30 expression assessed by immunohistochemistry was highly variable, with a median CD30max of 13% (range, 0% to 100%). Those with <5% CD30 expression had a lower likelihood of global response than did those with 5% or greater CD30 expression (P < .005). CD163 positive tumor-associated macrophages, many of which coexpress CD30, were abundant in tissue. Peripheral neuropathy was the most common adverse event. Conclusion Brentuximab vedotin demonstrated significant clinical activity in treatment-refractory or advanced MF or SS with a wide range of CD30 expression levels. Additional biomarker studies may help optimize rational design of combination therapies with brentuximab vedotin. (C) 2015 by American Society of Clinical Oncology C1 [Kim, Youn H.; Tavallaee, Mahkam; Sundram, Uma; Li, Shufeng; Rozati, Sima; Nagpal, Seema; Krathen, Michael; Reddy, Sunil; Hoppe, Richard T.; Nguyen-Lin, Annie; Weng, Wen-Kai; Armstrong, Randall; Advani, Ranjana H.] Stanford Univ, Stanford, CA 94305 USA. [Salva, Katrin A.; Wood, Gary S.] Univ Wisconsin, Madison, WI USA. [Salva, Katrin A.; Wood, Gary S.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Pulitzer, Melissa; Horwitz, Steven M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Kim, YH (reprint author), Stanford Canc Inst, Multidisciplinary Cutaneous Lymphoma Program, 780 Welch Rd,CJ220J, Stanford, CA 94305 USA. EM younkim@stanford.edu FU Seattle Genetics; Haas Family Foundation FX Supported by Seattle Genetics and the Haas Family Foundation. NR 30 TC 24 Z9 25 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 10 PY 2015 VL 33 IS 32 BP 3750 EP + DI 10.1200/JCO.2014.60.3969 PG 11 WC Oncology SC Oncology GA CX9IX UT WOS:000366020100014 PM 26195720 ER PT J AU Enzinger, AC Zhang, BH Schrag, D Prigerson, HG AF Enzinger, Andrea C. Zhang, Baohui Schrag, Deborah Prigerson, Holly G. TI Outcomes of Prognostic Disclosure: Associations With Prognostic Understanding, Distress, and Relationship With Physician Among Patients With Advanced Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID OF-LIFE COMMUNICATION; CARE NEAR-DEATH; LUNG-CANCER; INFORMATION PREFERENCES; PALLIATIVE CARE; END; PERCEPTIONS; ONCOLOGISTS; CHEMOTHERAPY; ILLNESS AB Purpose To determine how prognostic conversations influence perceptions of life expectancy (LE), distress, and the patient-physician relationship among patients with advanced cancer. Patients and Methods This was a multicenter observational study of 590 patients with metastatic solid malignancies with progressive disease after >= one line of palliative chemotherapy, undergoing follow-up to death. At baseline, patients were asked whether their oncologist had disclosed an estimate of prognosis. Patients also estimated their own LE and completed assessments of the patient-physician relationship, distress, advance directives, and end-of-life care preferences. Results Among this cohort of 590 patients with advanced cancer (median survival, 5.4 months), 71% wanted to be told their LE, but only 17.6% recalled a prognostic disclosure by their physician. Among the 299 (51%) of 590 patients willing to estimate their LE, those who recalled prognostic disclosure offered more realistic estimates as compared with patients who did not (median, 12 months; interquartile range, 6 to 36 months v 48 months; interquartile range, 12 to 180 months; P < .001), and their estimates were less likely to differ from their actual survival by > 2 (30.2% v 49.2%; odds ratio [OR], 0.45; 95% CI, 0.14 to 0.82) or 5 years (9.5% v 35.5%; OR, 0.19; 95% CI, 0.08 to 0.47). In adjusted analyses, recall of prognostic disclosure was associated with a 17.2-month decrease (95% CI, 6.2 to 28.2 months) in patients' LE self-estimates. Longer LE self-estimates were associated with lower likelihood of do-not-resuscitate order (adjusted OR, 0.439; 95% CI, 0.296 to 0.630 per 12-month increase in estimate) and preference for life-prolonging over comfort-oriented care (adjusted OR, 1.493; 95% CI, 1.091 to 1.939). Prognostic disclosure was not associated with worse patient-physician relationship ratings, sadness, or anxiety in adjusted analyses. Conclusion Prognostic disclosures are associated with more realistic patient expectations of LE, without decrements to their emotional well-being or the patient-physician relationship. (C) 2015 by American Society of Clinical Oncology C1 [Enzinger, Andrea C.; Schrag, Deborah] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Zhang, Baohui; Prigerson, Holly G.] Weill Cornell Med Coll, New York, NY 10065 USA. RP Prigerson, HG (reprint author), Weill Cornell Med Coll, 525 E 68th St,1404 Baker, New York, NY 10065 USA. EM hgp2001@med.cornell.edu FU National Cancer Institute [CA106370] FX Supported by National Cancer Institute Grant No. CA106370 (H.G.P.). NR 59 TC 19 Z9 19 U1 7 U2 13 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 10 PY 2015 VL 33 IS 32 BP 3809 EP + DI 10.1200/JCO.2015.61.9239 PG 9 WC Oncology SC Oncology GA CX9IX UT WOS:000366020100022 PM 26438121 ER PT J AU San Roman, AK Tovaglieri, A Breault, DT Shivdasani, RA AF San Roman, Adrianna K. Tovaglieri, Alessio Breault, David T. Shivdasani, Ramesh A. TI Distinct Processes and Transcriptional Targets Underlie CDX2 Requirements in Intestinal Stem Cells and Differentiated Villus Cells SO STEM CELL REPORTS LA English DT Article ID ADULT; CRYPT; GENE; LGR5; EXPRESSION; EPITHELIUM; IDENTITY; FATE AB Lgr5-expressing intestinal stem cells (ISCs) renew the adult gut epithelium by producing mature villus cells (VCs); the transcriptional basis for ISC functions remains unclear. RNA sequencing analysis identified transcripts modulated during differentiation of Lgr5(+) ISCs into VCs, with high expression of the intestine-restricted transcription factor (TF) gene Cdx2 in both populations. Cdx2-deleted mouse ISCs showed impaired proliferation and long-term inability to produce mature lineages, revealing essential ISC functions. Chromatin immunoprecipitation sequencing analysis of CDX2 in Lgr5(+) ISCs, coupled with mRNA profiling of control and Cdx2(-/-) ISCs, identified features of CDX2 regulation distinct from VCs. Most CDX2 binding in ISCs occurs in anticipation of future gene expression, but whereas CDX2 primarily activates VC genes, direct ISC targets are activated and repressed. Diverse CDX2 requirements in stem and differentiated cells may reflect the versatility of TFs that specify a tissue in development and control the same tissue in adults. C1 [San Roman, Adrianna K.; Shivdasani, Ramesh A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [San Roman, Adrianna K.; Shivdasani, Ramesh A.] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. [San Roman, Adrianna K.] Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA 02215 USA. [Tovaglieri, Alessio; Breault, David T.] Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Breault, David T.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02215 USA. [Shivdasani, Ramesh A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. [Shivdasani, Ramesh A.] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM ramesh_shivdasani@dfci.harvard.edu FU NIH [R01DK082889, R01DK084056, F31CA180784]; NSF graduate research fellowship FX This work was supported by NIH awards R01DK082889 (R.A.S.), R01DK084056 (D.T.B.), and F31CA180784 (A.K.S.R.) and a NSF graduate research fellowship (A.K.S.R.). We thank S. Robine for Villin-CreERT2 mice; P. Cejas and T.-H. Kim for sharing expertise and reagents; and M. Verzi and N. O'Neill for valuable discussions. NR 26 TC 3 Z9 3 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2213-6711 J9 STEM CELL REP JI Stem Cell Rep. PD NOV 10 PY 2015 VL 5 IS 5 BP 673 EP 681 DI 10.1016/j.stemcr.2015.09.006 PG 9 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA CW4UM UT WOS:000364991000001 PM 26489894 ER PT J AU Xiao, TF Liu, LH Li, HL Sun, Y Luo, HX Li, TP Wang, SH Dalton, S Zhao, RCH Chen, RS AF Xiao, Tengfei Liu, Lihui Li, Hongling Sun, Yu Luo, Huaxia Li, Tangping Wang, Shihua Dalton, Stephen Zhao, Robert Chunhua Chen, Runsheng TI Long Noncoding RNA ADINR Regulates Adipogenesis by Transcriptionally Activating C/EBP alpha SO STEM CELL REPORTS LA English DT Article ID MESENCHYMAL STEM-CELLS; GENE-EXPRESSION; PPAR-GAMMA; IN-VITRO; CHROMATIN; DIFFERENTIATION; METHYLATION; COMPLEXES; REVEALS; MOUSE AB C/EBP alpha is a critical transcriptional regulator of adipogenesis. HowC/EBP alpha transcriptionis itself regulated is poorly understood, however, and remains a key question that needs to be addressed for a complete understanding of adipogenic development. Here, we identify a lncRNA, ADINR(adipogenic differentiation induced noncoding RNA), transcribed from a position similar to 450 bp upstream of the C/EBP alpha gene, that orchestrates C/EBP alpha transcriptionin vivo. Depletion of ADINR leads to a severe adipogenic defect that is rescued by overexpression of C/EBP alpha. Moreover, we reveal that ADINR RNA specifically binds to PA1 and recruits MLL3/4 histone methyl-transferase complexes so as to increase H3K4me3 and decrease H3K27me3 histone modification in the C/EBP alpha locus during adipogenesis. These results show that ADINR plays important roles in regulating the differentiation of human mesenchymal stem cells into adipocytes by modulating C/EBP alpha in cis. C1 [Xiao, Tengfei; Liu, Lihui; Sun, Yu; Luo, Huaxia; Chen, Runsheng] Chinese Acad Sci, Inst Biophys, Key Lab RNA Biol, Beijing 100101, Peoples R China. [Xiao, Tengfei; Liu, Lihui; Sun, Yu; Luo, Huaxia; Chen, Runsheng] Chinese Acad Sci, Inst Biophys, Key Lab Noncoding RNA, Beijing 100101, Peoples R China. [Xiao, Tengfei] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02215 USA. [Li, Hongling; Li, Tangping; Wang, Shihua; Zhao, Robert Chunhua] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Peking Union Med Coll, Ctr Excellence Tissue Engn,Inst Basic Med Sci,Sch, Beijing 100005, Peoples R China. [Liu, Lihui; Sun, Yu; Luo, Huaxia] Chinese Acad Sci, Grad Sch, Beijing 100080, Peoples R China. [Dalton, Stephen] Univ Georgia, Dept Biochem & Mol Biol, Paul D Coverdell Ctr Biomed & Hlth Sci, Athens, GA 30602 USA. RP Zhao, RCH (reprint author), Chinese Acad Med Sci, Peking Union Med Coll Hosp, Peking Union Med Coll, Ctr Excellence Tissue Engn,Inst Basic Med Sci,Sch, Beijing 100005, Peoples R China. EM zhaochunhua@vip.163.com; rschen@ibp.ac.cn FU Chinese Academy of Sciences Strategic Project of Leading Science and Technology [XDA01020402]; National High Technology Research and Development Program ("863" Program) [2012AA020402]; National Natural Science Foundation of China [81370466]; National Collaborative Innovation Program FX We thank Myles Brown and Shirley Liu for helpful discussions and Jianqing Zhao for assistance with microarray data. This work was supported by the Chinese Academy of Sciences Strategic Project of Leading Science and Technology (XDA01020402), the National High Technology Research and Development Program ("863" Program) (2012AA020402), and the National Natural Science Foundation of China (No. 81370466). R.Z. was supported by a National Collaborative Innovation Program grant (for Biotherapy). NR 38 TC 15 Z9 17 U1 5 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2213-6711 J9 STEM CELL REP JI Stem Cell Rep. PD NOV 10 PY 2015 VL 5 IS 5 BP 856 EP 865 DI 10.1016/j.stemcr.2015.09.007 PG 10 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA CW4UM UT WOS:000364991000016 PM 26489893 ER PT J AU Gaziano, JM Peterson, ED Greenland, P AF Gaziano, J. Michael Peterson, Eric D. Greenland, Philip TI Advancing Cardiovascular Science SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 [Gaziano, J. Michael; Peterson, Eric D.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02120 USA. [Gaziano, J. Michael; Peterson, Eric D.] Brigham & Womens Hosp, Div Aging, Boston, MA 02120 USA. [Peterson, Eric D.] Duke Univ, Med Ctr, Durham, NC USA. [Greenland, Philip] Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL USA. RP Gaziano, JM (reprint author), Brigham & Womens Hosp, Div Aging, 1620 Tremont St, Boston, MA 02120 USA. EM jmgaziano@partners.org NR 16 TC 0 Z9 0 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 10 PY 2015 VL 314 IS 18 BP 1924 EP 1925 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CV7XQ UT WOS:000364490700014 PM 26547463 ER PT J AU Voog, JC Efstathiou, JA AF Voog, Justin C. Efstathiou, Jason A. TI Treatment Trends for Prostate Cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID PHASE-3 TRIAL; MANAGEMENT C1 [Voog, Justin C.] Brigham & Womens Hosp, Harvard Radiat Oncol Program, Boston, MA 02115 USA. [Efstathiou, Jason A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Voog, JC (reprint author), Brigham & Womens Hosp, Harvard Radiat Oncol Program, ASBI L2, Boston, MA 02115 USA. EM jvoog@partners.org NR 5 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 10 PY 2015 VL 314 IS 18 BP 1976 EP 1977 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CV7XQ UT WOS:000364490700024 PM 26547472 ER PT J AU Xiang, Y Kiseleva, R Reukov, V Mulligan, J Atkinson, C Schlosser, R Vertegel, A AF Xiang, Yun Kiseleva, Raisa Reukov, Vladimir Mulligan, Jennifer Atkinson, Carl Schlosser, Rodney Vertegel, Alexey TI Relationship between Targeting Efficacy of Liposomes and the Dosage of Targeting Antibody Using Surface Plasmon Resonance SO LANGMUIR LA English DT Article ID DRUG-DELIVERY; IN-VITRO; NANOPARTICLES; BINDING; RECEPTOR; AVIDITY; CELLS; SIZE; IMMUNOLIPOSOMES; NANOCARRIERS AB Surface plasmon resonance (SPR) was used in this research to investigate the targeting efficacy (i.e., the binding affinity) of antibody-modified liposomes. The results indicated that liposomes modified by targeting antibodies exhibited an increase in apparent binding affinity, a result attributed to the avidity effect. More specifically, the targeting effect improved as the surface density of the targeting antibody increased, an increase primarily attributed to the decrease of the dissociation rate. However, this trend stopped when the surface density reached a threshold of approximately 1.5 x 10(8) antibody/mm(2). This surface density was found to be quite consistent regardless of the liposome size and the type of targeting antibody. In addition, a traditional cell binding experiment was conducted to confirm the saturation point obtained from SPR. C1 [Xiang, Yun; Kiseleva, Raisa; Reukov, Vladimir; Vertegel, Alexey] Clemson Univ, Dept Bioengn, Clemson, SC 29634 USA. [Mulligan, Jennifer; Atkinson, Carl; Schlosser, Rodney] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Vertegel, A (reprint author), Clemson Univ, Dept Bioengn, Clemson, SC 29634 USA. EM vertege@clemson.edu FU VA Grant [101 CX000377]; NIH [2P20RR016461-10] FX The authors gratefully acknowledge the assistance from the Biomolecular Interactions Lab and Biomolecular Modeling Lab, Department of Bioengineering, Clemson University. This project was supported by a VA Grant (Merit Award 101 CX000377). Partial support was provided by NIH Grant No. 2P20RR016461-10 (INBRE), awarded to the South Carolina Research Foundation. NR 38 TC 2 Z9 2 U1 3 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0743-7463 J9 LANGMUIR JI Langmuir PD NOV 10 PY 2015 VL 31 IS 44 BP 12177 EP 12186 DI 10.1021/acs.langmuir.5b01386 PG 10 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA CV9NY UT WOS:000364615100027 PM 26484937 ER PT J AU Fung, M Kim, J Marty, FM Schwarzinger, M Koo, S AF Fung, Monica Kim, Jane Marty, Francisco M. Schwarzinger, Michael Koo, Sophia TI Meta-Analysis and Cost Comparison of Empirical versus Pre-Emptive Antifungal Strategies in Hematologic Malignancy Patients with High-Risk Febrile Neutropenia SO PLoS One LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; INVASIVE FUNGAL DISEASE; CELL TRANSPLANT RECIPIENTS; IMMUNOCOMPROMISED PATIENTS; PULMONARY ASPERGILLOSIS; PROSPECTIVE FEASIBILITY; COMPUTED-TOMOGRAPHY; THERAPY; GALACTOMANNAN; INFECTIONS AB Background Invasive fungal disease (IFD) causes significant morbidity and mortality in hematologic malignancy patients with high-risk febrile neutropenia (FN). These patients therefore often receive empirical antifungal therapy. Diagnostic test-guided pre-emptive antifungal therapy has been evaluated as an alternative treatment strategy in these patients. Methods We conducted an electronic search for literature comparing empirical versus pre-emptive antifungal strategies in FN among adult hematologic malignancy patients. We systematically reviewed 9 studies, including randomized-controlled trials, cohort studies, and feasibility studies. Random and fixed-effect models were used to generate pooled relative risk estimates of IFD detection, IFD-related mortality, overall mortality, and rates and duration of antifungal therapy. Heterogeneity was measured via Cochran's Q test, I-2 statistic, and between study tau(2). Incorporating these parameters and direct costs of drugs and diagnostic testing, we constructed a comparative costing model for the two strategies. We conducted probabilistic sensitivity analysis on pooled estimates and one-way sensitivity analyses on other key parameters with uncertain estimates. Results Nine published studies met inclusion criteria. Compared to empirical antifungal therapy, pre-emptive strategies were associated with significantly lower antifungal exposure (RR 0.48, 95% CI 0.27-0.85) and duration without an increase in IFD-related mortality (RR 0.82, 95% CI 0.36-1.87) or overall mortality (RR 0.95, 95% CI 0.46-1.99). The pre-emptive strategy cost $324 less (95% credible interval -$291.88 to $418.65 pre-emptive compared to empirical) than the empirical approach per FN episode. However, the cost difference was influenced by relatively small changes in costs of antifungal therapy and diagnostic testing. Conclusions Compared to empirical antifungal therapy, pre-emptive antifungal therapy in patients with high-risk FN may decrease antifungal use without increasing mortality. We demonstrate a state of economic equipoise between empirical and diagnostic-directed pre-emptive antifungal treatment strategies, influenced by small changes in cost of antifungal therapy and diagnostic testing, in the current literature. This work emphasizes the need for optimization of existing fungal diagnostic strategies, development of more efficient diagnostic strategies, and less toxic and more cost-effective antifungals. C1 [Fung, Monica] Beth Israel Deaconess Med Ctr, Dept Internal Med, Boston, MA 02215 USA. [Fung, Monica; Marty, Francisco M.; Koo, Sophia] Harvard Univ, Sch Med, Boston, MA USA. [Kim, Jane] Harvard Univ, Dept Hlth Policy & Management, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Marty, Francisco M.; Koo, Sophia] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Marty, Francisco M.; Koo, Sophia] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schwarzinger, Michael] Translat Hlth Econ Network, Paris, France. [Schwarzinger, Michael] INSERM, Decis Sci Infect Dis Prevent Control & Care, IAME, Paris, France. [Schwarzinger, Michael] Univ Paris Diderot, IAME, Paris, France. RP Fung, M (reprint author), Beth Israel Deaconess Med Ctr, Dept Internal Med, Boston, MA 02215 USA. EM mfung@bidmc.harvard.edu RI Schwarzinger, Michael/F-7367-2011; OI Koo, Sophia/0000-0002-4973-7439 FU National Institute of Allergy and Infectious Diseases [K23 AI097225]; Translational Health Economics Network FX Sophia Koo is supported by K23 AI097225 from the National Institute of Allergy and Infectious Diseases (http://www.niaid.nih.gov/). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Michael Schwarzinger is employed by the company Translational Health Economics Network. This funder provided support in the form of salary for Dr. Schwarzinger, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of this author are articulated in the author contributions section. NR 39 TC 1 Z9 1 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 10 PY 2015 VL 10 IS 11 AR e0140930 DI 10.1371/journal.pone.0140930 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CV7CT UT WOS:000364430700018 PM 26554923 ER PT J AU Antonucci, L Fagman, JB Kim, JY Todoric, J Gukovsky, I Mackey, M Ellisman, MH Karin, M AF Antonucci, Laura Fagman, Johan B. Kim, Ju Youn Todoric, Jelena Gukovsky, Ilya Mackey, Mason Ellisman, Mark H. Karin, Michael TI Basal autophagy maintains pancreatic acinar cell homeostasis and protein synthesis and prevents ER stress SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE autophagy; ATG7; pancreatitis; protein synthesis ID ENDOPLASMIC-RETICULUM STRESS; OXIDATIVE STRESS; CANCER; MICE; PATHWAY; P53; INFLAMMATION; INVOLVEMENT; ROLES AB Pancreatic acinar cells possess very high protein synthetic rates as they need to produce and secrete large amounts of digestive enzymes. Acinar cell damage and dysfunction cause malnutrition and pancreatitis, and inflammation of the exocrine pancreas that promotes development of pancreatic ductal adenocarcinoma (PDAC), a deadly pancreatic neoplasm. The cellular and molecular mechanisms that maintain acinar cell function and whose dysregulation can lead to tissue damage and chronic pancreatitis are poorly understood. It was suggested that autophagy, the principal cellular degradative pathway, is impaired in pancreatitis, but it is unknown whether impaired autophagy is a cause or a consequence of pancreatitis. To address this question, we generated Atg7(Delta pan) mice that lack the essential autophagy-related protein 7 (ATG7) in pancreatic epithelial cells. Atg7(Delta pan) mice exhibit severe acinar cell degeneration, leading to pancreatic inflammation and extensive fibrosis. Whereas ATG7 loss leads to the expected decrease in autophagic flux, it also results in endoplasmic reticulum (ER) stress, accumulation of dysfunctional mitochondria, oxidative stress, activation of AMPK, and a marked decrease in protein synthetic capacity that is accompanied by loss of rough ER. Atg7(Delta pan) mice also exhibit spontaneous activation of regenerative mechanisms that initiate acinar-to-ductal metaplasia (ADM), a process that replaces damaged acinar cells with duct-like structures. C1 [Antonucci, Laura; Fagman, Johan B.; Kim, Ju Youn; Todoric, Jelena; Karin, Michael] Univ Calif San Diego, Sch Med, Lab Gene Regulat & Signal Transduct, Moores Canc Ctr,Dept Pharmacol, La Jolla, CA 92093 USA. [Antonucci, Laura; Fagman, Johan B.; Kim, Ju Youn; Todoric, Jelena; Karin, Michael] Univ Calif San Diego, Sch Med, Lab Gene Regulat & Signal Transduct, Moores Canc Ctr,Dept Pathol, La Jolla, CA 92093 USA. [Fagman, Johan B.] Univ Gothenburg, Inst Clin Sci, Dept Surg, Sahlgrenska Canc Ctr, SE-41345 Gothenburg, Sweden. [Todoric, Jelena] Med Univ Vienna, Dept Lab Med, A-1090 Vienna, Austria. [Gukovsky, Ilya] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Gukovsky, Ilya] Univ Calif Los Angeles, Los Angeles, CA 90073 USA. [Mackey, Mason; Ellisman, Mark H.] Univ Calif San Diego, Natl Ctr Microscopy & Imaging Res, La Jolla, CA 92093 USA. RP Karin, M (reprint author), Univ Calif San Diego, Sch Med, Lab Gene Regulat & Signal Transduct, Moores Canc Ctr,Dept Pharmacol, La Jolla, CA 92093 USA. EM karinoffice@ucsd.edu FU Istituto Pasteur-Fondazione Cenci Bolognetti; Swedish Research Council [524-2011-6817]; Swedish Society for Medical Research; Superfund Basic Research Project (SBRP) [ES010337]; Austrian Science Fund [J3233]; Austrian Association for Laboratory Medicine and Clinical Chemistry (OGLMKC); Austrian Program for Advanced Research and Technology of the Austrian Academy of Sciences; NIH [AA019730, DK098108, GM103412, GM103426, CA163798, P01 DK098108]; International Community Foundation, San Diego; SBRP [ES010337]; Lustgarten Foundation [RFP-B-007] FX We thank Guy Perkins and Tom Deerinck for advice and helpful suggestions and thank Santa Cruz Biotechnology and Cell Signaling for antibody samples. L.A. was supported by a fellowship from Istituto Pasteur-Fondazione Cenci Bolognetti; J.B.F. was supported by post-doctoral fellowships from the Swedish Research Council (524-2011-6817) and the Swedish Society for Medical Research. J.Y.K. was supported by the Superfund Basic Research Project (SBRP; ES010337); J.T. was supported by the Erwin Schroedinger Fellowship from the Austrian Science Fund (J3233) and Univ. Prof. Dr. 17 Matthias M. Muller Fellowship from the Austrian Association for Laboratory Medicine and Clinical Chemistry (OGLMKC) and the Austrian Program for Advanced Research and Technology of the Austrian Academy of Sciences; I.G. was supported by NIH Grants AA019730 and DK098108; M.M. and M.H.E. were supported by grants from the International Community Foundation, San Diego, the NIH (GM103412 and GM103426). M.K. is an American Cancer Society Research Professor and the Ben and Wanda Hildyard Chair for Mitochondrial and Metabolic Diseases. Research in his lab was supported by grants from the NIH (CA163798), the SBRP (ES010337), the Lustgarten Foundation (RFP-B-007), and NIH Program Project Grant P01 DK098108. NR 44 TC 17 Z9 17 U1 1 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 10 PY 2015 VL 112 IS 45 BP E6166 EP E6174 DI 10.1073/pnas.1519384112 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CV7QY UT WOS:000364470300014 PM 26512112 ER PT J AU Dec, GW AF Dec, G. William TI LCZ696 (Sacubitril/Valsartan) Can We Predict Who Will Benefit? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE neprilysn inhibition; sacubitril/valsartan ID HEART-FAILURE; NEPRILYSIN INHIBITION; RISK SCORE; ENALAPRIL; TRIAL C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Dec, GW (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey 5B,55 Fruit St, Boston, MA 02114 USA. EM gdec@partners.org NR 11 TC 2 Z9 3 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 10 PY 2015 VL 66 IS 19 BP 2072 EP 2074 DI 10.1016/j.jacc.2015.08.877 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CU9MO UT WOS:000363868800002 PM 26541916 ER PT J AU Ong, Q Hochberg, FH Cima, MJ AF Ong, Qunya Hochberg, Fred H. Cima, Michael J. TI Depot delivery of dexamethasone and cediranib for the treatment of brain tumor associated edema in an intracranial rat glioma model SO JOURNAL OF CONTROLLED RELEASE LA English DT Article DE Drug delivery; Depot; Dexamethasone; Cediranib; Brain tumor associated edema ID ENDOTHELIAL-GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; BIODEGRADABLE POLYMERS; MALIGNANT GLIOMA; MUSCLE ATROPHY; LOCAL-DELIVERY; EXPRESSION; RECEPTOR; AZD2171; SURVIVAL AB Treatments of brain tumor associated edema with systemically delivered dexamethasone, the standard of care, and cediranib, a novel anti-edema agent, are associated with systemic toxicities in brain tumor patients. A tunable, reservoir-based drug delivery device was developed to investigate the effects of delivering dexamethasone and cediranib locally in the brain in an intracranial 9 L gliosarcoma rat model. Reproducible, sustained releases of both dexamethasone and solid dispersion of cediranib in polyvinylpyrrolidone (AZD/PVP) from these devices were achieved. The water-soluble AZD/PVP, which exhibited similar bioactivity as cediranib, was developed to enhance the release of cediranib from the device. Local and systemic administration of both dexamethasone and cediranib was equally efficacious in alleviating edema but had no effect on tumor growth. Edema reduction led to modest but significant improvement in survival. Local delivery of dexamethasone prevented dexamethasone-induced weight loss, an adverse effect seen in animals treated with systemic dexamethasone. Local deliveries of dexamethasone and cediranib via these devices used only 2.36% and 0.21% of the systemic doses respectively, but achieved similar efficacy as systemic drug deliveries without the side effects associated with systemic administration. Other therapeutic agents targeting brain tumor can be delivered locally in the brain to provide similar improved treatment outcomes. (c) 2015 Elsevier B.V. All rights reserved. C1 [Ong, Qunya] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. [Ong, Qunya; Cima, Michael J.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Hochberg, Fred H.] Massachusetts Gen Hosp, Neurol, Boston, MA 02114 USA. [Cima, Michael J.] MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. RP Cima, MJ (reprint author), MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave,Bldg 76 Room 653G, Cambridge, MA 02139 USA. EM mjcima@mit.edu NR 39 TC 1 Z9 1 U1 4 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 EI 1873-4995 J9 J CONTROL RELEASE JI J. Control. Release PD NOV 10 PY 2015 VL 217 BP 183 EP 190 DI 10.1016/j.jconrel.2015.08.028 PG 8 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA CU4FC UT WOS:000363481500018 PM 26285064 ER PT J AU Park, KS Charles, RC Ryan, ET Weissleder, R Lee, H AF Park, Ki Soo Charles, Richelle C. Ryan, Edward T. Weissleder, Ralph Lee, Hakho TI Fluorescence Polarization Based Nucleic Acid Testing for Rapid and Cost-Effective Diagnosis of Infectious Disease SO CHEMISTRY-A EUROPEAN JOURNAL LA English DT Article DE aptamer; biosensors; DNA polymerase; infectious disease; nucleic acid testing ID AQUATICUS DNA-POLYMERASE; REAL-TIME PCR; GRAPHENE OXIDE; TYPHOID-FEVER; BACTERIA; BANGLADESH; EXPRESSION; BLOOD; ASSAY; NANOPARTICLES AB A new nucleic acid detection method was developed for a rapid and cost-effective diagnosis of infectious disease. This approach relies on the three unique elements: 1)detection probes that regulate DNA polymerase activity in response to the complementary target DNA; 2)universal reporters conjugated with a single fluorophore; and 3)fluorescence polarization (FP) detection. As a proof-of-concept, the assay was used to detect and sub-type Salmonella bacteria with sensitivities down to a single bacterium in less than three hours. C1 [Park, Ki Soo; Weissleder, Ralph; Lee, Hakho] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Park, Ki Soo; Weissleder, Ralph; Lee, Hakho] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Charles, Richelle C.; Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Charles, Richelle C.; Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. EM rweissleder@mgh.harvard.edu; hlee@mgh.harvard.edu FU NIH [R01L113156, R01EB004626, R01EB010011, HHSN268201000044C, R33100023]; DoD OCRP [W81XWH-14-1-0279]; Basic Science Research Program through the National Research Foundation of Korea - Ministry of Education [2014R1A6A3A03059728] FX This work was supported in part by NIH Grants R01L113156, R01EB004626, R01EB010011, HHSN268201000044C, and R33100023; DoD OCRP Award W81XWH-14-1-0279; Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (2014R1A6A3A03059728). NR 34 TC 5 Z9 5 U1 5 U2 28 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 0947-6539 EI 1521-3765 J9 CHEM-EUR J JI Chem.-Eur. J. PD NOV 9 PY 2015 VL 21 IS 46 BP 16359 EP 16363 DI 10.1002/chem.201502934 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA CW6TY UT WOS:000365132100008 PM 26420633 ER PT J AU Buchy, L Cannon, TD Anticevic, A Lyngberg, K Cadenhead, KS Cornblatt, BA McGlashan, TH Perkins, DO Seidman, LJ Tsuang, MT Walker, EF Woods, SW Bearden, CE Mathalon, DH Addington, J AF Buchy, Lisa Cannon, Tyrone D. Anticevic, Alan Lyngberg, Kristina Cadenhead, Kristin S. Cornblatt, Barbara A. McGlashan, Thomas H. Perkins, Diana O. Seidman, Larry J. Tsuang, Ming T. Walker, Elaine F. Woods, Scott W. Bearden, Carrie E. Mathalon, Daniel H. Addington, Jean TI Evaluating the impact of cannabis use on thalamic connectivity in youth at clinical high risk of psychosis SO BMC PSYCHIATRY LA English DT Article DE Cannabis; Clinical high risk; Functional connectivity; Resting state functional magnetic resonance imaging; Psychosis; Schizophrenia; Thalamus ID BRAIN STRUCTURAL ALTERATIONS; SUBSTANCE USE; 1ST-EPISODE SCHIZOPHRENIA; ADULT PSYCHOSIS; YOUNG-ADULTS; CB1 RECEPTOR; INDIVIDUALS; PEOPLE; VOLUME; DYSCONNECTIVITY AB Background: Disruptions in thalamic functional connectivity have been observed in people with schizophrenia and in youth at clinical high risk (CHR) of psychosis. However, the impact of environmental risk factors for psychosis on thalamic dysconnectivity is poorly understood. We tested whether thalamic dysconnectivity is related to patterns of cannabis use in a CHR sample. Methods: 162 CHR and 105 control participants were assessed on cannabis use severity, frequency, and age at onset of first use as part of the North American Prodrome Longitudinal Study and completed resting-state fMRI scans. Whole-brain thalamic functional connectivity maps were generated using individual subjects' anatomically defined thalamic seeds. Results: Thalamic connectivity did not significantly correlate with current cannabis use severity or frequency in either CHR or controls. In CHR cannabis users, a significant correlation emerged between attenuated thalamic connectivity with left sensory/motor cortex and a younger age at onset of cannabis use. CHR who used cannabis before age 15 did not differ on thalamic connectivity as compared to CHR who used after age 15 or CHR who were cannabis naive. No group differences in thalamic connectivity emerged when comparing CHR separated by moderate/high use frequency, low-frequency or cannabis naive. Conclusions: Although a younger age at onset of cannabis use may be associated with disrupted thalamo-cortical coupling, cannabis use does not appear to be an identifying characteristic for thalamic connectivity in CHR with moderate/high use frequency compared to low-frequency users or CHR who are cannabis naive. C1 [Buchy, Lisa; Addington, Jean] Univ Calgary, Dept Psychiat, Calgary, AB, Canada. [Cannon, Tyrone D.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Anticevic, Alan; McGlashan, Thomas H.; Woods, Scott W.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Lyngberg, Kristina] Univ Calgary, Fac Sci, Dept Neurosci, Calgary, AB, Canada. [Cadenhead, Kristin S.] UCSD, Dept Psychiat, La Jolla, CA USA. [Cornblatt, Barbara A.; Tsuang, Ming T.] Zucker Hillside Hosp, Dept Psychiat, Long Isl City, NY USA. [Perkins, Diana O.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Seidman, Larry J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Walker, Elaine F.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. [Walker, Elaine F.] Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA. [Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Mathalon, Daniel H.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Addington, Jean] Univ Calgary, Mathison Ctr Mental Hlth Res & Educ, Calgary, AB T2N 4Z6, Canada. RP Addington, J (reprint author), Univ Calgary, Dept Psychiat, Calgary, AB, Canada. EM jmadding@ucalgary.ca FU National Institute of Mental Health [U01MH081984, U01 MH081928, P50 MH080272]; Commonwealth of Massachusetts [SCDMH82101008006, R01 MH60720, U01 MH082022, K24 MH76191, U01MH081902, P50 MH066286, U01MH082004, U01MH081988, U01MH082022, UO1 MH081857-05] FX This study was supported by the National Institute of Mental Health (grant U01MH081984 to Dr Addington; grants U01 MH081928; P50 MH080272; Commonwealth of Massachusetts SCDMH82101008006 to Dr Seidman; grants R01 MH60720, U01 MH082022 and K24 MH76191 to Dr Cadenhead; grant U01MH081902 to Dr Cannon; P50 MH066286 (Prodromal Core) to Dr Bearden; grant U01MH082004 to Dr Perkins; grant U01MH081988 to Dr Walker; grant U01MH082022 to Dr Woods; and UO1 MH081857-05 grant to Dr Cornblatt. The NIMH 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 50 TC 0 Z9 0 U1 5 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-244X J9 BMC PSYCHIATRY JI BMC Psychiatry PD NOV 9 PY 2015 VL 15 AR 276 DI 10.1186/s12888-015-0656-x PG 9 WC Psychiatry SC Psychiatry GA CV9RY UT WOS:000364625500002 PM 26553191 ER PT J AU Best, MG Sol, N Kooi, I Tannous, J Westerman, BA Rustenburg, F Schellen, P Verschueren, H Post, E Koster, J Ylstra, B Ameziane, N Dorsman, J Smit, EF Verheul, HM Noske, DP Reijneveld, JC Nilsson, RJA Tannous, BA Wesseling, P Wurdinger, T AF Best, Myron G. Sol, Nik Kooi, Irsan Tannous, Jihane Westerman, Bart A. Rustenburg, Francois Schellen, Pepijn Verschueren, Heleen Post, Edward Koster, Jan Ylstra, Bauke Ameziane, Najim Dorsman, Josephine Smit, Egbert F. Verheul, Henk M. Noske, David P. Reijneveld, Jaap C. Nilsson, R. Jonas A. Tannous, Bakhos A. Wesseling, Pieter Wurdinger, Thomas TI RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics SO CANCER CELL LA English DT Article ID GENE-EXPRESSION SIGNATURES; METASTATIC BREAST-CANCER; MESSENGER-RNA; LUNG-CANCER; TRANSCRIPTIONAL LANDSCAPE; CLINICAL VALIDATION; ANUCLEATE PLATELETS; ACTIVATED PLATELETS; CLASS PREDICTION; PLASMA DNA AB Tumor-educated blood platelets (TEPs) are implicated as central players in the systemic and local responses to tumor growth, thereby altering their RNA profile. We determined the diagnostic potential of TEPs by mRNA sequencing of 283 platelet samples. We distinguished 228 patients with localized and metastasized tumors from 55 healthy individuals with 96% accuracy. Across six different tumor types, the location of the primary tumor was correctly identified with 71% accuracy. Also, MET or HER2-positive, and mutant KRAS, EGFR, or PIK3CA tumors were accurately distinguished using surrogate TEP mRNA profiles. Our results indicate that blood platelets provide a valuable platform for pan-cancer, multiclass cancer, and companion diagnostics, possibly enabling clinical advances in blood-based "liquid biopsies". C1 [Best, Myron G.; Rustenburg, Francois; Ylstra, Bauke; Wesseling, Pieter] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Pathol, NL-1081 HV Amsterdam, Netherlands. [Best, Myron G.; Westerman, Bart A.; Rustenburg, Francois; Schellen, Pepijn; Verschueren, Heleen; Post, Edward; Noske, David P.; Nilsson, R. Jonas A.; Wurdinger, Thomas] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Neurosurg, NL-1081 HV Amsterdam, Netherlands. [Sol, Nik; Reijneveld, Jaap C.] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Neurol, NL-1081 HV Amsterdam, Netherlands. [Kooi, Irsan; Ameziane, Najim; Dorsman, Josephine] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Clin Genet, NL-1081 HV Amsterdam, Netherlands. [Tannous, Jihane; Tannous, Bakhos A.; Wurdinger, Thomas] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Tannous, Jihane; Tannous, Bakhos A.; Wurdinger, Thomas] Harvard Univ, Sch Med, Neurosci Program, Charlestown, MA 02129 USA. [Schellen, Pepijn; Verschueren, Heleen; Post, Edward; Nilsson, R. Jonas A.; Wurdinger, Thomas] thromboDx BV, NL-1098 EA Amsterdam, Netherlands. [Koster, Jan] Univ Amsterdam, Acad Med Ctr, Dept Oncogen, NL-1105 AZ Amsterdam, Netherlands. [Smit, Egbert F.] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Pulm Dis, NL-1081 HV Amsterdam, Netherlands. [Verheul, Henk M.] Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Med Oncol, NL-1081 HV Amsterdam, Netherlands. [Nilsson, R. Jonas A.] Umea Univ, Dept Radiat Sci, S-90185 Umea, Sweden. [Wesseling, Pieter] Radboud Univ Nijmegen, Med Ctr, Dept Pathol, NL-6500 HB Nijmegen, Netherlands. RP Wurdinger, T (reprint author), Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Neurosurg, Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands. EM t.wurdinger@vumc.nl RI Ylstra, Bauke/D-2906-2012; OI Ylstra, Bauke/0000-0001-9479-3010; Wesseling, P./0000-0001-5453-5201 FU European Research Council [E8626, 336540]; Dutch Organisation of Scientific Research [93612003, 91711366]; Dutch Cancer Society; Stichting STOPhersentumoren.nl; NIH/NCI [CA176359, CA069246]; CFF Norrland; Swedish Research Council FX Financial support was provided by European Research Council E8626 (R.J.A.N., E.F.S., and T.W.) and 336540 (T.W.), the Dutch Organisation of Scientific Research 93612003 and 91711366 (T.W.), the Dutch Cancer Society (J.C.R., H.M.V., and T.W.), Stichting STOPhersentumoren.nl (M.G.B. and P.W.), the NIH/NCI CA176359 and CA069246 (BAT.), CFF Norrland (R.J.A.N.), and Swedish Research Council (R.J.A.N.). We are thankful to Esther Drees, Magda Grabowska, Danijela Koppers-Lalic, Michiel Pegtel, Wessel van Wieringen, Phillip de Witt Hamer, and W. Peter Vandertop. NR 68 TC 32 Z9 32 U1 6 U2 35 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 EI 1878-3686 J9 CANCER CELL JI Cancer Cell PD NOV 9 PY 2015 VL 28 IS 5 BP 666 EP 676 DI 10.1016/j.ccell.2015.09.018 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CV9LQ UT WOS:000364609100014 PM 26525104 ER PT J AU Gaudin, R Kirchhausen, T AF Gaudin, Raphael Kirchhausen, Tomas TI Superinfection exclusion is absent during acute Junin virus infection of Vero and A549 cells SO SCIENTIFIC REPORTS LA English DT Article ID HEMORRHAGIC-FEVER; NEW-WORLD; ARENAVIRUSES; PROTEIN; POLYMERASE; EXPRESSION; RESISTANCE; DOMAINS AB Many viruses have evolved strategies of so-called "superinfection exclusion" to prevent re-infection of a cell that the same virus has already infected. Although Old World arenavirus infection results in down-regulation of its viral receptor and thus superinfection exclusion, whether New World arenaviruses have evolved such a mechanism remains unclear. Here we show that acute infection by the New World Junin virus (JUNV) failed to down-regulate the transferrin receptor and did not induce superinfection exclusion. We observed that Vero cells infected by a first round of JUNV (Candid1 strain) preserve an ability to internalize new incoming JUNV particles that is comparable to that of non-infected cells. Moreover, we developed a dual infection assay with the wild-type Candid1 JUNV and a recombinant JUNV-GFP virus to discriminate between first and second infections at the transcriptional and translational levels. We found that Vero and A549 cells already infected by JUNV were fully competent to transcribe viral RNA from a second round of infection. Furthermore, flow cytometry analysis of viral protein expression indicated that viral translation was normal, regardless of whether cells were previously infected or not. We conclude that in acutely infected cells, Junin virus lacks a superinfection exclusion mechanism. C1 [Gaudin, Raphael; Kirchhausen, Tomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Gaudin, Raphael; Kirchhausen, Tomas] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Kirchhausen, Tomas] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Gaudin, R (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 200 Longwood Ave, Boston, MA 02115 USA. EM raphael.gaudin@childrens.harvard.edu; kirchhausen@crystal.harvard.edu FU NIH [U54 AI057159] FX We thank David Cureton for help during the early stages of this project, particularly with the development of the protocol to generate Junin virus; Sean Whelan for the BSR-T7 cells and his advice; Bernard Moss for the recombinant vaccinia T7 virus; and Cesar Albarino for the expression vectors to generate JUNV-GFP viruses. We thank Eric Marino for maintaining the imaging resources in the Kirchhausen laboratory. The mouse monoclonal antibodies LD05 (NR-2569), SA02 (NR-2573), and GB03 (NR-2564) were obtained from BEI Resources, NIAID. This work was supported by NIH grant U54 AI057159 to the New England Regional Center of Excellence in Biodefense and Emerging Infectious Diseases [NERCE BEID]). NR 23 TC 1 Z9 1 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD NOV 9 PY 2015 VL 5 AR 15990 DI 10.1038/srep15990 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CV5EB UT WOS:000364288900001 PM 26549784 ER PT J AU McNamara, AL Schuemann, J Paganetti, H AF McNamara, Aimee L. Schuemann, Jan Paganetti, Harald TI A phenomenological relative biological effectiveness (RBE) model for proton therapy based on all published in vitro cell survival data SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE relative biological effectiveness; proton therapy; cell survival; linear energy transfer ID LOW-ENERGY PROTONS; LOW-DOSE HYPERSENSITIVITY; CHINESE-HAMSTER CELLS; V79 MAMMALIAN-CELLS; OUT BRAGG PEAK; LNL-FACILITY; TUMOR-CELLS; MUTATION-INDUCTION; LET RELATIONSHIP; MELANOMA-CELLS AB Proton therapy treatments are currently planned and delivered using the assumption that the proton relative biological effectiveness (RBE) relative to photons is 1.1. This assumption ignores strong experimental evidence that suggests the RBE varies along the treatment field, i.e. with linear energy transfer (LET) and with tissue type. A recent review study collected over 70 experimental reports on proton RBE, providing a comprehensive dataset for predicting RBE for cell survival. Using this dataset we developed a model to predict proton RBE based on dose, dose average LET (LETd) and the ratio of the linear-quadratic model parameters for the reference radiation (alpha/beta)(x), as the tissue specific parameter. The proposed RBE model is based on the linear quadratic model and was derived from a nonlinear regression fit to 287 experimental data points. The proposed model predicts that the RBE increases with increasing LETd and decreases with increasing (alpha/beta)(x). This agrees with previous theoretical predictions on the relationship between RBE, LETd and (alpha/beta)(x). The model additionally predicts a decrease in RBE with increasing dose and shows a relationship between both alpha and beta with LETd. Our proposed phenomenological RBE model is derived using the most comprehensive collection of proton RBE experimental data to date. Previously published phenomenological models, based on a limited data set, may have to be revised. C1 [McNamara, Aimee L.; Schuemann, Jan; Paganetti, Harald] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP McNamara, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 30 Fruit St, Boston, MA 02114 USA. EM amcnamara2@mgh.harvard.edu RI McNamara, Aimee/C-9432-2009 OI McNamara, Aimee/0000-0001-8792-0464 FU National Institutes of Health [R01 CA-140735]; National Cancer Institute [U19 CA-21239] FX This work was funded by the National Institutes of Health: R01 CA-140735 and the National Cancer Institute under U19 CA-21239. NR 69 TC 14 Z9 14 U1 6 U2 11 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD NOV 7 PY 2015 VL 60 IS 21 BP 8399 EP 8416 DI 10.1088/0031-9155/60/21/8399 PG 18 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA CY0PR UT WOS:000366108500013 PM 26459756 ER PT J AU Krah, N Testa, M Brons, S Jakel, O Parodi, K Voss, B Rinaldi, I AF Krah, N. Testa, M. Brons, S. Jaekel, O. Parodi, K. Voss, B. Rinaldi, I. TI An advanced image processing method to improve the spatial resolution of ion radiographies SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article DE ion beam therapy; imaging; ion radiography; proton radiography; image processing method; spatial resolution ID PROTON COMPUTED-TOMOGRAPHY; MONTE-CARLO SIMULATIONS; CT-HOUNSFIELD UNITS; RANGE TELESCOPE; THERAPY; SYSTEM; PARTICLE; PATIENT; CALIBRATION; DETECTOR AB We present an optimization method to improve the spatial resolution and the water equivalent thickness (WET) accuracy of ion radiographies. The method is designed for imaging systems measuring for each actively scanned beam spot the lateral position of the pencil beam and at the same time the Bragg curve (behind the target) in discrete steps without relying on tracker detectors to determine the ion trajectory before and after the irradiated volume. Specifically, the method was used for an imaging set-up consisting of a stack of 61 parallel-plate ionization chambers (PPIC) interleaved with absorber plates of polymethyl methacrylate (PMMA) working as a range telescope. The method uses not only the Bragg peak position, but approximates the entire measured Bragg curve as a superposition of differently shifted Bragg curves. Their relative weights allow to reconstruct the distribution of thickness around each scan spot of a heterogeneous phantom. The approach also allows merging the ion radiography with the geometric information of a co-registered x-ray radiography in order to increase its spatial resolution. The method was tested using Monte Carlo simulated and experimental proton radiographies of a PMMA step phantom and an anthropomorphic head phantom. For the step phantom, the effective spatial resolution was found to be 6 and 4 times higher than the nominal resolution for the simulated and experimental radiographies, respectively. For the head phantom, a gamma index was calculated to quantify the conformity of the simulated proton radiographies with a digitally reconstructed radiography (DRR) obtained from an x-ray CT and properly converted into WET. For a distance-to-agreement (DTA) of 2.5 mm and a relative WET difference (RWET) of 2.5%, the passing ratio was 100%/85% for the optimized/non-optimized case, respectively. When the optimized proton radiography was merged with the co-registered DRR, the passing ratio was 100% at DTA = 1.3 mm and RWET = 1.3%. A special interpolation method allows to strongly reduce the dose by using a coarser grid of the measured beam spot position with a 5 times larger grid distance. We show that despite a dose reduction of 25 times (leading to a dose of 0.016 mGy for the current imaging set-up), the image quality of the optimized radiographies remains fairly unaffected for both the simulated and experimental case. C1 [Krah, N.] Heidelberg Collaboratory Image Proc, D-69115 Heidelberg, Germany. [Testa, M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Brons, S.; Jaekel, O.; Parodi, K.] Heidelberg Ion Therapy Ctr, D-69120 Heidelberg, Germany. [Jaekel, O.; Rinaldi, I.] Univ Heidelberg Hosp, Dept Radiat Therapy & Oncol, D-69120 Heidelberg, Germany. [Jaekel, O.] German Canc Res Ctr, D-69120 Heidelberg, Germany. [Parodi, K.; Rinaldi, I.] Univ Munich, D-85748 Garching, Germany. [Voss, B.] GSI Helmholtz Ctr Heavy Ion Res, D-64291 Darmstadt, Germany. RP Krah, N (reprint author), Heidelberg Collaboratory Image Proc, Speyerer Str 6, D-69115 Heidelberg, Germany. EM rinaldi@ipnl.in2p3.fr FU German Research Foundation (DFG) within the project 'A novel imaging technique for ion beam therapy: Ion Computed Tomography'; Yonsei University Research Fund; HIT FX The experimental and simulation work of IR was supported by the German Research Foundation (DFG) within the project 'A novel imaging technique for ion beam therapy: Ion Computed Tomography'. MT was partially supported by Yonsei University Research Fund 2015. We would like to thank HIT for supporting the experiments and Dr J Bauer and Dr C Kurz for helping with the x-ray CT measurements at the PET/CT scanner at HIT. We are also grateful to the referees for their useful and constructive comments. NR 39 TC 2 Z9 2 U1 1 U2 4 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD NOV 7 PY 2015 VL 60 IS 21 BP 8525 EP 8547 DI 10.1088/0031-9155/60/21/8525 PG 23 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA CY0PR UT WOS:000366108500020 PM 26485618 ER PT J AU Urayama, A Dohgu, S Robinson, SM Sly, WS Grubb, JH Banks, WA AF Urayama, Akihiko Dohgu, Shinya Robinson, Sandra M. Sly, William S. Grubb, Jeffery H. Banks, William A. TI Alpha Adrenergic Induction of Transport of Lysosomal Enzyme across the Blood-Brain Barrier SO PLoS One LA English DT Article ID MANNOSE 6-PHOSPHATE RECEPTOR; MEDIATED TRANSPORT; INTERNALIZATION; SUBTYPES; STORAGE; VII AB The impermeability of the adult blood-brain barrier (BBB) to lysosomal enzymes impedes the ability to treat the central nervous system manifestations of lysosomal storage diseases. Here, we found that simultaneous stimulation of the alpha1 and alpha2 adrenoreceptor restores in adult mice the high rate of transport for the lysosomal enzyme P-GUS that is seen in neonates but lost with development. Beta adrenergics, other monoamines, and acetylcholine did not restore this transport. A high dose (500 microg/mouse) of clonidine, a strong alpha2 and weak alpha1 agonist, was able to act as monotherapy in the stimulation of P-GUS transport. Neither use of alpha1 plus alpha2 agonists nor the high dose clonidine disrupted the BBB to albumin. In situ brain perfusion and immunohistochemistry studies indicated that adrengerics act on transporters already at the luminal surface of brain endothelial cells. These results show that adrenergic stimulation, including monotherapy with clonidine, could be key for CNS enzyme replacement therapy. C1 [Urayama, Akihiko] Univ Texas Med Sch Houston, Dept Neurol, Houston, TX USA. [Dohgu, Shinya] Fac Pharmaceut Sci, Dept Pharmaceut Care & Hlth Sci, Fukuoka, Japan. [Robinson, Sandra M.] St Louis Univ, Div Geriatr Med, Dept Internal Med, St Louis, MO 63103 USA. [Sly, William S.; Grubb, Jeffery H.] St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO USA. [Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98493 USA. [Banks, William A.] Univ Washington, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. RP Banks, WA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98493 USA. EM wabanks1@uw.edu FU National Institutes of Health [Ro1 NS081134]; Veterans Affairs; Shire; NIH [R01 NS081134] FX National Institutes of Health (WAB) Ro1 NS081134, Veterans Affairs (WAB) (no number), Shire (WAB; WSS) (no number). The funders had no role in the study, design, data collection and analysis, decision to publish, or preparation of the manuscript.; Supported by Veterans Affairs (WAB), Shire, and NIH R01 NS081134 (WAB). The contents do not represent the views of the US Department of Veterans Affairs or the United States Government. NR 25 TC 1 Z9 1 U1 2 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 6 PY 2015 VL 10 IS 11 AR e0142347 DI 10.1371/journal.pone.0142347 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CV6RT UT WOS:000364398700116 PM 26545208 ER PT J AU Mitchell, CJ Getnet, D Kim, MS Manda, SS Kumar, P Huang, TC Pinto, SM Nirujogi, RS Iwasaki, M Shaw, PG Wu, XY Zhong, J Chaerkady, R Marimuthu, A Muthusamy, B Sahasrabuddhe, NA Raju, R Bowman, C Danilova, L Cutler, J Kelkar, DS Drake, CG Prasad, TSK Marchionni, L Murakami, PN Scott, AF Shi, LM Thierry-Mieg, J Thierry-Mieg, D Irizarry, R Cope, L Ishihama, Y Wang, C Gowda, H Pandey, A AF Mitchell, Christopher J. Getnet, Derese Kim, Min-Sik Manda, Srikanth S. Kumar, Praveen Huang, Tai-Chung Pinto, Sneha M. Nirujogi, Raja Sekhar Iwasaki, Mio Shaw, Patrick G. Wu, Xinyan Zhong, Jun Chaerkady, Raghothama Marimuthu, Arivusudar Muthusamy, Babylakshmi Sahasrabuddhe, Nandini A. Raju, Rajesh Bowman, Caitlyn Danilova, Ludmila Cutler, Jevon Kelkar, Dhanashree S. Drake, Charles G. Prasad, T. S. Keshava Marchionni, Luigi Murakami, Peter N. Scott, Alan F. Shi, Leming Thierry-Mieg, Jean Thierry-Mieg, Danielle Irizarry, Rafael Cope, Leslie Ishihama, Yasushi Wang, Charles Gowda, Harsha Pandey, Akhilesh TI A multi-omic analysis of human naive CD4+T cells SO BMC SYSTEMS BIOLOGY LA English DT Article DE Whole genome sequencing; Epigenomics; Transcriptomics; Proteomics; Phosphoproteomics; Integrativeomics; Innate immunity ID SPECTROMETRY-BASED PROTEOMICS; KAPPA-B ACTIVATION; RNA-SEQ DATA; MASS-SPECTROMETRY; T-CELLS; GENE-EXPRESSION; PHOSPHORYLATION; DIFFERENTIATION; TRANSCRIPTOME; LYMPHOCYTES AB Background: Cellular function and diversity are orchestrated by complex interactions of fundamental biomolecules including DNA, RNA and proteins. Technological advances in genomics, epigenomics, transcriptomics and proteomics have enabled massively parallel and unbiased measurements. Such high-throughput technologies have been extensively used to carry out broad, unbiased studies, particularly in the context of human diseases. Nevertheless, a unified analysis of the genome, epigenome, transcriptome and proteome of a single human cell type to obtain a coherent view of the complex interplay between various biomolecules has not yet been undertaken. Here, we report the first multi-omic analysis of human primary naive CD4+ T cells isolated from a single individual. Results: Integrating multi-omics datasets allowed us to investigate genome-wide methylation and its effect on mRNA/protein expression patterns, extent of RNA editing under normal physiological conditions and allele specific expression in naive CD4+ T cells. In addition, we carried out a multi-omic comparative analysis of naive with primary resting memory CD4+ T cells to identify molecular changes underlying T cell differentiation. This analysis provided mechanistic insights into how several molecules involved in T cell receptor signaling are regulated at the DNA, RNA and protein levels. Phosphoproteomics revealed downstream signaling events that regulate these two cellular states. Availability of multi-omics data from an identical genetic background also allowed us to employ novel proteogenomics approaches to identify individual-specific variants and putative novel protein coding regions in the human genome. Conclusions: We utilized multiple high-throughput technologies to derive a comprehensive profile of two primary human cell types, naive CD4+ T cells and memory CD4+ T cells, from a single donor. Through vertical as well as horizontal integration of whole genome sequencing, methylation arrays, RNA-Seq, miRNA-Seq, proteomics, and phosphoproteomics, we derived an integrated and comparative map of these two closely related immune cells and identified potential molecular effectors of immune cell differentiation following antigen encounter. C1 [Mitchell, Christopher J.; Getnet, Derese; Kim, Min-Sik; Huang, Tai-Chung; Shaw, Patrick G.; Wu, Xinyan; Zhong, Jun; Chaerkady, Raghothama; Bowman, Caitlyn; Cutler, Jevon; Scott, Alan F.; Pandey, Akhilesh] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21218 USA. [Manda, Srikanth S.; Kumar, Praveen; Pinto, Sneha M.; Nirujogi, Raja Sekhar; Marimuthu, Arivusudar; Muthusamy, Babylakshmi; Sahasrabuddhe, Nandini A.; Raju, Rajesh; Kelkar, Dhanashree S.; Prasad, T. S. Keshava; Gowda, Harsha; Pandey, Akhilesh] Int Tech Pk, Inst Bioinformat, Bangalore, Karnataka, India. [Iwasaki, Mio; Ishihama, Yasushi] Kyoto Univ, Dept Mol & Cellular BioAnal, Kyoto, Japan. [Murakami, Peter N.] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Danilova, Ludmila; Drake, Charles G.; Marchionni, Luigi; Cope, Leslie] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Shi, Leming] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Thierry-Mieg, Jean; Thierry-Mieg, Danielle] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. [Irizarry, Rafael] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Wang, Charles] Loma Linda Univ, Ctr Genom, Loma Linda, CA 92350 USA. [Wang, Charles] Loma Linda Univ, Div Microbiol & Mol Genet, Loma Linda, CA 92350 USA. [Pandey, Akhilesh] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA. [Pandey, Akhilesh] Johns Hopkins Univ, Sch Med, Dept Pathol & Oncol, Baltimore, MD USA. RP Pandey, A (reprint author), Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21218 USA. EM pandey@jhmi.edu RI Ishihama, Yasushi/B-3101-2016; Kim, Min-Sik/M-3488-2016; Zhong, Jun/D-1662-2010; THIERRY-MIEG, Jean/F-1975-2017; OI Ishihama, Yasushi/0000-0001-7714-203X; Kim, Min-Sik/0000-0001-7317-5360; Zhong, Jun/0000-0003-3148-4143; THIERRY-MIEG, Jean/0000-0002-0396-6789; Huang, Tai-Chung/0000-0002-1625-7295 FU NIH [U54GM103520]; NCI's Clinical Proteomic Tumor Analysis Consortium initiative [U24CA160036]; National Heart, Lung and Blood Institute (NHLBI) [HHSN268201000032C]; Department of Biotechnology (DBT), Government of India FX We thank Dr. Barbara Migeon, Dr. Drew Pardoll, and Dr. Robert Siliciano for helpful discussions. We thank the Proteomics Core Facility at the Johns Hopkins University School of Medicine for data acquisition. This work was supported by a NIH roadmap grant for Technology Centers of Networks and Pathways (TCNP) (U54GM103520), NCI's Clinical Proteomic Tumor Analysis Consortium initiative (U24CA160036) and a contract (HHSN268201000032C) from the National Heart, Lung and Blood Institute (NHLBI). Harsha Gowda is a Wellcome Trust/DBT India Alliance Early Career Fellow. This work is also supported by research grants from the Department of Biotechnology (DBT), Government of India. NR 52 TC 3 Z9 3 U1 3 U2 16 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1752-0509 J9 BMC SYST BIOL JI BMC Syst. Biol. PD NOV 6 PY 2015 VL 9 AR 75 DI 10.1186/s12918-015-0225-4 PG 16 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA CV5BK UT WOS:000364280300001 PM 26542228 ER PT J AU Hu, JZ Zhang, Y Zhao, LJ Frock, RL Du, Z Meyers, RM Meng, FL Schatz, DG Alt, FW AF Hu, Jiazhi Zhang, Yu Zhao, Lijuan Frock, Richard L. Du, Zhou Meyers, Robin M. Meng, Fei-long Schatz, David G. Alt, Frederick W. TI Chromosomal Loop Domains Direct the Recombination of Antigen Receptor Genes SO CELL LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CELL IDENTITY GENES; V(D)J RECOMBINATION; TRANSCRIPTION FACTORS; DNA BREAKS; GENOME; CTCF; MECHANISMS; COMPLEXES; REVEALS AB RAG initiates antibody V(D)J recombination in developing lymphocytes by generating "on-target'' DNA breaks at matched pairs of bona fide recombination signal sequences (RSSs). We employ bait RAG-generated breaks in endogenous or ectopically inserted RSS pairs to identify huge numbers of RAG "off-target'' breaks. Such breaks occur at the simple CAC motif that defines the RSS cleavage site and are largely confined within convergent CTCF-binding element (CBE)-flanked loop domains containing bait RSS pairs. Marked orientation dependence of RAG off-target activity within loops spanning up to 2 megabases implies involvement of linear tracking. In this regard, major RAG off-targets in chromosomal translocations occur as convergent RSS pairs at enhancers within a loop. Finally, deletion of a CBE-based IgH locus element disrupts V(D) J recombination domains and, correspondingly, alters RAG on-and off-target distributions within IgH. Our findings reveal how RAG activity is developmentally focused and implicate mechanisms by which chromatin domains harness biological processes within them. C1 [Hu, Jiazhi; Zhang, Yu; Zhao, Lijuan; Frock, Richard L.; Du, Zhou; Meyers, Robin M.; Meng, Fei-long; Schatz, David G.; Alt, Frederick W.] Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Hu, Jiazhi; Zhang, Yu; Zhao, Lijuan; Frock, Richard L.; Du, Zhou; Meyers, Robin M.; Meng, Fei-long; Alt, Frederick W.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Hu, Jiazhi; Zhang, Yu; Zhao, Lijuan; Frock, Richard L.; Du, Zhou; Meyers, Robin M.; Meng, Fei-long; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Schatz, David G.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA. RP Alt, FW (reprint author), Boston Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu OI Frock, Richard/0000-0001-6963-4931 FU NIH [AI020047, AI032524]; LLS SCOR [7009-12]; Robertson Foundation/Cancer Research Institute Irvington Fellowship; Leukemia and Lymphoma Society; NIH NRSA [AI007512] FX The authors thank the Alt lab members and Richard Young (MIT) and Jay Bradner (DFCI) for stimulating discussions. This work was supported by NIH grant AI020047 and LLS SCOR 7009-12 to F.W.A. and NIH grant AI032524 to D.G.S. F.W.A. and D.G.S. are Howard Hughes Medical Institute Investigators. J.H. is supported by a Robertson Foundation/Cancer Research Institute Irvington Fellowship. Y.Z. is supported by a career development fellowship from the Leukemia and Lymphoma Society. R.L.F. was supported by the NIH NRSA AI007512. F.-L.M. is a Lymphoma Research Foundation postdoctoral fellow. NR 46 TC 28 Z9 28 U1 3 U2 19 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD NOV 5 PY 2015 VL 163 IS 4 BP 947 EP 959 DI 10.1016/j.cell.2015.10.016 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CW2NS UT WOS:000364829700019 PM 26593423 ER PT J AU Nishimura, W Kapoor, A El Khattabi, I Jin, WZ Yasuda, K Bonner-Weir, S Sharma, A AF Nishimura, Wataru Kapoor, Archana El Khattabi, Ilham Jin, Wanzhu Yasuda, Kazuki Bonner-Weir, Susan Sharma, Arun TI Compensatory Response by Late Embryonic Tubular Epithelium to the Reduction in Pancreatic Progenitors SO PLoS One LA English DT Article ID ENDOCRINE CELL-TYPES; BETA-CELLS; EXOCRINE PANCREAS; MOUSE PANCREAS; DUCTAL CELLS; DIFFERENTIATION; BIRTH; REGENERATION; EXPRESSION; NEOGENESIS AB Early in pancreatic development, epithelial cells of pancreatic buds function as primary multipotent progenitor cells (1 degrees MPC) that specify all three pancreatic cell lineages, i.e., endocrine, acinar and duct. Bipotent "Trunk" progenitors derived from 1 degrees MPC are implicated in directly regulating the specification of endocrine progenitors. It is unclear if this specification process is initiated in the 1 degrees MPC where some 1 degrees MPC become competent for later specification of endocrine progenitors. Previously we reported that in Pdx1(tTA/+); tetO(MafA) (bigenic) mice inducing expression of transcription factor MafA in Pdx1-expressing (Pdx1(+)) cells throughout embryonic development inhibited the proliferation and differentiation of 1 degrees MPC cells, resulting in reduced pancreatic mass and endocrine cells by embryonic day (E) 17.5. Induction of the transgene only until E12.5 in Pdx1(+) 1 degrees MPC was sufficient for this inhibition of endocrine cells and pancreatic mass at E17.5. However, by birth (P0), as we now report, such bigenic pups had significantly increased pancreatic and endocrine volumes with endocrine clusters containing all pancreatic endocrine cell types. The increase in endocrine cells resulted from a higher proliferation of tubular epithelial cells expressing the progenitor marker Glut2 in E17.5 bigenic embryos and increased number of Neurog3-expressing cells at E19.5. A BrdU-labeling study demonstrated that inhibiting proliferation of 1 degrees MPC by forced MafA-expression did not lead to retention of those progenitors in E17.5 tubular epithelium. Our data suggest that the forced MafA expression in the 1 degrees MPC inhibits their competency to specify endocrine progenitors only until E17.5, and after that compensatory proliferation of tubular epithelium gives rise to a distinct pool of endocrine progenitors. Thus, these bigenic mice provide a novel way to characterize the competency of 1 degrees MPC for their ability to specify endocrine progenitors, a critical limitation in our understanding of endocrine differentiation. C1 [Nishimura, Wataru; Kapoor, Archana; El Khattabi, Ilham; Jin, Wanzhu; Bonner-Weir, Susan; Sharma, Arun] Joslin Diabet Ctr, Sect Islet Cell & Regenerat Biol, Boston, MA 02215 USA. [Nishimura, Wataru; Kapoor, Archana; El Khattabi, Ilham; Jin, Wanzhu; Bonner-Weir, Susan; Sharma, Arun] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Nishimura, Wataru; Yasuda, Kazuki] Natl Ctr Global Hlth & Med, Res Inst, Diabet Res Ctr, Dept Metab Disorder, Tokyo, Japan. [Nishimura, Wataru] Jichi Univ, Div Anat Bioimaging & Neurocell Sci, Shimotsuke, Tochigi, Japan. RP Sharma, A (reprint author), MedImmune, Cardiovasc & Metab Dis, Gaithersburg, MD 20878 USA. EM arun.sharma@joslin.harvard.edu OI Bonner-Weir, Susan/0000-0003-4682-0656; Nishimura, Wataru/0000-0002-8068-1277 FU NIH [RO1 DK060127]; Juvenile Diabetes Research Foundation (JDRF); American Diabetes Association [1-12-BS-187]; Herbert Graetz Fund; Shirley and William Fleisher Family Foundation; Alexander and Margaret Stewart Trust; JDRF; JSPS [22591022]; Takeda Science Foundation; National Center for Global Health and Medicine; Okinaka Memorial Institute for Medical Research; Japan Diabetes Foundation; Media and Advanced Microscopy Cores of Joslin Diabetes Endocrinology Research Center (NIH) [DK-36836] FX This study was supported by research grants from NIH (RO1 DK060127), Juvenile Diabetes Research Foundation (JDRF), American Diabetes Association grant 1-12-BS-187, the Herbert Graetz Fund, Shirley and William Fleisher Family Foundation, and the Alexander and Margaret Stewart Trust to AS; JDRF postdoctoral fellowship, Mary K. Iacocca Fellowship, and grants from JSPS KAKENHI (22591022), Takeda Science Foundation, National Center for Global Health and Medicine, the Okinaka Memorial Institute for Medical Research and Japan Diabetes Foundation to WN; and Media and Advanced Microscopy Cores of Joslin Diabetes Endocrinology Research Center (NIH DK-36836); and an important group of private donors. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 33 TC 0 Z9 0 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 5 PY 2015 VL 10 IS 11 AR e0142286 DI 10.1371/journal.pone.0142286 PG 20 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CV5IS UT WOS:000364303800075 PM 26540252 ER PT J AU Motzer, RJ Escudier, B McDermott, DF George, S Hammers, HJ Srinivas, S Tykodi, SS Sosman, JA Procopio, G Plimack, ER Castellano, D Choueiri, TK Gurney, H Donskov, F Bono, P Wagstaff, J Gauler, TC Ueda, T Tomita, Y Schutz, FA Kollmannsberger, C Larkin, J Ravaud, A Simon, JS Xu, LA Waxman, IM Sharma, P AF Motzer, R. J. Escudier, B. McDermott, D. F. George, S. Hammers, H. J. Srinivas, S. Tykodi, S. S. Sosman, J. A. Procopio, G. Plimack, E. R. Castellano, D. Choueiri, T. K. Gurney, H. Donskov, F. Bono, P. Wagstaff, J. Gauler, T. C. Ueda, T. Tomita, Y. Schutz, F. A. Kollmannsberger, C. Larkin, J. Ravaud, A. Simon, J. S. Xu, L-A Waxman, I. M. Sharma, P. CA CheckMate 025 Investigators TI Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ANTI-PROGRAMMED DEATH-1; PROGNOSTIC-FACTORS; FOLLOW-UP; CANCER; SURVIVAL; CONFIDENCE; GUIDELINES; SAFETY; B7-H1 AB BACKGROUND Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, was associated with encouraging overall survival in uncontrolled studies involving previously treated patients with advanced renal-cell carcinoma. This randomized, open-label, phase 3 study compared nivolumab with everolimus in patients with renal-cell carcinoma who had received previous treatment. METHODS A total of 821 patients with advanced clear-cell renal-cell carcinoma for which they had received previous treatment with one or two regimens of antiangiogenic therapy were randomly assigned (in a 1: 1 ratio) to receive 3 mg of nivolumab per kilogram of body weight intravenously every 2 weeks or a 10-mg everolimus tablet orally once daily. The primary end point was overall survival. The secondary end points included the objective response rate and safety. RESULTS The median overall survival was 25.0 months (95% confidence interval [CI], 21.8 to not estimable) with nivolumab and 19.6 months (95% CI, 17.6 to 23.1) with everolimus. The hazard ratio for death with nivolumab versus everolimus was 0.73 (98.5% CI, 0.57 to 0.93; P=0.002), which met the prespecified criterion for superiority (P <= 0.0148). The objective response rate was greater with nivolumab than with everolimus (25% vs. 5%; odds ratio, 5.98 [95% CI, 3.68 to 9.72]; P<0.001). The median progression-free survival was 4.6 months (95% CI, 3.7 to 5.4) with nivolumab and 4.4 months (95% CI, 3.7 to 5.5) with everolimus (hazard ratio, 0.88; 95% CI, 0.75 to 1.03; P=0.11). Grade 3 or 4 treatment-related adverse events occurred in 19% of the patients receiving nivolumab and in 37% of the patients receiving everolimus; the most common event with nivolumab was fatigue (in 2% of the patients), and the most common event with everolimus was anemia (in 8%). CONCLUSIONS Among patients with previously treated advanced renal-cell carcinoma, overall survival was longer and fewer grade 3 or 4 adverse events occurred with nivolumab than with everolimus. C1 [Motzer, R. J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [George, S.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Escudier, B.] Inst Gustave Roussy, Villejuif, France. [Ravaud, A.] Hop St Andre, Bordeaux Univ Hosp, Bordeaux, France. [McDermott, D. F.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Choueiri, T. K.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Choueiri, T. K.] Harvard Univ, Sch Med, Boston, MA USA. [Hammers, H. J.] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Srinivas, S.] Stanford Canc Inst, Stanford, CA USA. [Tykodi, S. S.] Univ Washington, Seattle, WA 98195 USA. [Tykodi, S. S.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Sosman, J. A.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Procopio, G.] Fdn Ist Nazl Tumori, Milan, Italy. [Plimack, E. R.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Castellano, D.] Hosp Univ 12 Octubre, Madrid, Spain. [Gurney, H.] Westmead Hosp, Sydney, NSW, Australia. [Gurney, H.] Macquarie Univ, Sydney, NSW 2109, Australia. [Donskov, F.] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. [Bono, P.] Helsinki Univ Cent Hosp, Helsinki, Finland. [Bono, P.] Univ Helsinki, Helsinki, Finland. [Wagstaff, J.] South West Wales Canc Inst, Swansea, W Glam, Wales. [Wagstaff, J.] Swansea Univ, Coll Med, Swansea, W Glam, Wales. [Larkin, J.] Royal Marsden Hosp, London SW3 6JJ, England. [Gauler, T. C.] Univ Duisburg Essen, Univ Hosp Essen, Duisburg, Germany. [Ueda, T.] Chiba Canc Ctr, Chiba 2608717, Japan. [Tomita, Y.] Niigata Univ, Niigata, Japan. [Schutz, F. A.] Hosp Sao Jose, Beneficencia Portuguesa Sao Paulo, Sao Paulo, Brazil. [Kollmannsberger, C.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Simon, J. S.; Waxman, I. M.] Bristol Myers Squibb Co, Lawrenceville, NJ USA. [Xu, L-A] Bristol Myers Squibb Co, Hopewell, NJ USA. [Sharma, P.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Motzer, RJ (reprint author), Mem Hosp, Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. EM motzerr@mskcc.org RI Straume, Oddbjorn/C-2186-2017; Procopio, Giuseppe/K-2072-2016; OI Straume, Oddbjorn/0000-0001-8867-3645; Procopio, Giuseppe/0000-0002-2498-402X; Meiler, Jens/0000-0001-8945-193X FU Bristol-Myers Squibb FX Funded by Bristol-Myers Squibb NR 32 TC 491 Z9 501 U1 12 U2 46 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 5 PY 2015 VL 373 IS 19 BP 1803 EP 1813 DI 10.1056/NEJMoa1510665 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA CV3FK UT WOS:000364144000004 PM 26406148 ER PT J AU Choueiri, TK Escudier, B Powles, T Mainwaring, PN Rini, BI Donskov, F Hammers, H Hutson, TE Lee, JL Peltola, K Roth, BJ Bjarnason, GA Geczi, L Keam, B Maroto, P Heng, DYC Schmidinger, M Kantoff, PW Borgman-Hagey, A Hessel, C Scheffold, C Schwab, GM Tannir, NM Motzer, RJ AF Choueiri, T. K. Escudier, B. Powles, T. Mainwaring, P. N. Rini, B. I. Donskov, F. Hammers, H. Hutson, T. E. Lee, J-L Peltola, K. Roth, B. J. Bjarnason, G. A. Geczi, L. Keam, B. Maroto, P. Heng, D. Y. C. Schmidinger, M. Kantoff, P. W. Borgman-Hagey, A. Hessel, C. Scheffold, C. Schwab, G. M. Tannir, N. M. Motzer, R. J. CA METEOR Investigators TI Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PHASE-III TRIAL; PROGNOSTIC-FACTORS; HGF/C-MET; C-MET; SUNITINIB; TUMORS; METASTASIS; XL184; NEPHRECTOMY; SORAFENIB AB BACKGROUND Cabozantinib is an oral, small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL, each of which has been implicated in the pathobiology of metastatic renal-cell carcinoma or in the development of resistance to antiangiogenic drugs. This randomized, open-label, phase 3 trial evaluated the efficacy of cabozantinib, as compared with everolimus, in patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy. METHODS We randomly assigned 658 patients to receive cabozantinib at a dose of 60 mg daily or everolimus at a dose of 10 mg daily. The primary end point was progression-free survival. Secondary efficacy end points were overall survival and objective response rate. RESULTS Median progression-free survival was 7.4 months with cabozantinib and 3.8 months with everolimus. The rate of progression or death was 42% lower with cabozantinib than with everolimus (hazard ratio, 0.58; 95% confidence interval [CI] 0.45 to 0.75; P<0.001). The objective response rate was 21% with cabozantinib and 5% with everolimus (P<0.001). A planned interim analysis showed that overall survival was longer with cabozantinib than with everolimus (hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P = 0.005) but did not cross the significance boundary for the interim analysis. Adverse events were managed with dose reductions; doses were reduced in 60% of the patients who received cabozantinib and in 25% of those who received everolimus. Discontinuation of study treatment owing to adverse events occurred in 9% of the patients who received cabozantinib and in 10% of those who received everolimus. CONCLUSIONS Progression-free survival was longer with cabozantinib than with everolimus among patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy. C1 [Choueiri, T. K.; Kantoff, P. W.] Dana Farber Canc Inst, Boston, MA 02215 USA. [Escudier, B.] Inst Gustave Roussy, Villejuif, France. [Powles, T.] Queen Mary Univ London, Royal Free NHS Trust, Canc Res UK Expt Canc Med Ctr, Barts Canc Inst, London, England. [Mainwaring, P. N.] Icon Canc Care, South Brisbane, Qld, Australia. [Rini, B. I.] Cleveland Clin, Cleveland, OH USA. [Donskov, F.] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. [Hammers, H.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Hutson, T. E.] Baylor Univ, Charles A Sammons Canc Ctr, Texas Oncol, Dallas, TX USA. [Lee, J-L] Univ Ulsan, Coll Med, Seoul, South Korea. [Keam, B.] Seoul Natl Univ Hosp, Seoul 110744, South Korea. [Peltola, K.] Univ Helsinki, Cent Hosp, Ctr Canc, Helsinki, Finland. [Roth, B. J.] Washington Univ, St Louis, MO 63130 USA. [Bjarnason, G. A.] Sunnybrook Odette Canc Ctr, Toronto, ON, Canada. [Heng, D. Y. C.] Tom Baker Canc Clin, Calgary, AB, Canada. [Geczi, L.] Natl Inst Oncol, Budapest, Hungary. [Maroto, P.] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [Schmidinger, M.] Med Univ Vienna, Vienna, Austria. [Borgman-Hagey, A.; Hessel, C.; Scheffold, C.; Schwab, G. M.] Exelixis, San Francisco, CA USA. [Tannir, N. M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Motzer, R. J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Choueiri, TK (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,DANA 1230, Boston, MA 02215 USA. EM toni_choueiri@dfci.-harvard.edu FU Exelixis FX Funded by Exelixis NR 29 TC 151 Z9 152 U1 6 U2 18 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 5 PY 2015 VL 373 IS 19 BP 1814 EP 1823 DI 10.1056/NEJMoa1510016 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA CV3FK UT WOS:000364144000005 PM 26406150 ER PT J AU Murray, SG Wachter, RM Cho, KC Dhaliwal, G AF Murray, Sara G. Wachter, Robert M. Cho, Kerry C. Dhaliwal, Gurpreet TI A Breakthrough Diagnosis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID BLADDER RUPTURE; URINARY ASCITES; RENAL-FAILURE; MULTIPLE-SCLEROSIS C1 [Murray, Sara G.; Wachter, Robert M.; Cho, Kerry C.; Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Murray, Sara G.; Wachter, Robert M.] Univ Calif San Francisco, Div Hosp Med, San Francisco, CA 94143 USA. [Cho, Kerry C.] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, San Francisco, CA USA. RP Murray, SG (reprint author), Univ Calif San Francisco, 533 Parnassus Ave,U125, San Francisco, CA 94143 USA. EM sara.murray@ucsf.edu FU Governance Institute; Optima Health; QuantiaMD; IPC Healthcare; PatientSafe Solutions; Twine Health; EarlySense; QPID Health; Amino.com FX Dr. Wachter reports receiving fees paid to his institution for his membership on the board of directors and his service as chair of the quality committee for IPC Healthcare, receiving fees for serving on advisory boards for and holding stock options in PatientSafe Solutions, Twine Health, EarlySense, QPID Health, and Amino.com, receiving lecture fees from the Governance Institute and Optima Health, and receiving fees for developing and presenting patient safety educational material from QuantiaMD. No other potential conflict of interest relevant to this article was reported. NR 12 TC 0 Z9 0 U1 1 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 5 PY 2015 VL 373 IS 19 BP 1866 EP 1871 DI 10.1056/NEJMcps1402621 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA CV3FK UT WOS:000364144000012 ER PT J AU Greene, MF Longo, DL AF Greene, Michael F. Longo, Dan L. TI Cautious Optimism for Offspring of Women with Cancer during Pregnancy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Greene, Michael F.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Greene, MF (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 5 PY 2015 VL 373 IS 19 BP 1875 EP 1876 DI 10.1056/NEJMe1512188 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA CV3FK UT WOS:000364144000014 PM 26415086 ER PT J AU Leonard, TK Mikkila, JM Eskandar, EN Gerrard, JL Kaping, D Patel, SR Womelsdorf, T Hoffman, KL AF Leonard, Timothy K. Mikkila, Jonathan M. Eskandar, Emad N. Gerrard, Jason L. Kaping, Daniel Patel, Shaun R. Womelsdorf, Thilo Hoffman, Kari L. TI Sharp Wave Ripples during Visual Exploration in the Primate Hippocampus SO JOURNAL OF NEUROSCIENCE LA English DT Article DE change detection; macaque; natural scenes; search; sleep; theta ID SACCADIC EYE-MOVEMENTS; NONNEGATIVE MATRIX FACTORIZATION; HIGH-FREQUENCY OSCILLATIONS; MEDIAL TEMPORAL-LOBE; SLOW OSCILLATIONS; SPATIAL MEMORY; CORTICAL INTERACTION; THETA-OSCILLATIONS; ENSEMBLE ACTIVITY; BEHAVING RAT AB Hippocampal sharp-wave ripples (SWRs) are highly synchronous oscillatory field potentials that are thought to facilitate memory consolidation. SWRs typically occur during quiescent states, when neural activity reflecting recent experience is replayed. In rodents, SWRs also occur during brief locomotor pauses in maze exploration, where they appear to support learning during experience. In this study, we detected SWRs that occurred during quiescent states, but also during goal-directed visual exploration in nonhuman primates (Macaca mulatta). The exploratory SWRs showed peak frequency bands similar to those of quiescent SWRs, and both types were inhibited at the onset of their respective behavioral epochs. In apparent contrast to rodent SWRs, these exploratory SWRs occurred during active periods of exploration, e. g., while animals searched for a target object in a scene. SWRs were associated with smaller saccades and longer fixations. Also, when they coincided with target-object fixations during search, detection was more likely than when these events were decoupled. Although we observed high gamma-band field potentials of similar frequency to SWRs, only the SWRs accompanied greater spiking synchrony in neural populations. These results reveal that SWRs are not limited to off-line states as conventionally defined; rather, they occur during active and informative performance windows. The exploratory SWR in primates is an infrequent occurrence associated with active, attentive performance, which may indicate a new, extended role of SWRs during exploration in primates. C1 [Leonard, Timothy K.; Mikkila, Jonathan M.; Hoffman, Kari L.] York Univ, Ctr Vis Res, Dept Psychol, Toronto, ON M3J 1P3, Canada. [Kaping, Daniel; Womelsdorf, Thilo; Hoffman, Kari L.] York Univ, Ctr Vis Res, Dept Biol, Toronto, ON M3J 1P3, Canada. [Eskandar, Emad N.; Gerrard, Jason L.; Patel, Shaun R.] Massachusetts Gen Hosp, Dept Neurosurg, Nayef Al Rodhan Labs, Boston, MA 02114 USA. RP Hoffman, KL (reprint author), Ctr Vis Res, Dept Biol, Dept Psychol, Toronto, ON M3J 1P3, Canada. EM khoffman@yorku.ca OI Hoffman, Kari/0000-0003-0560-8157 FU National Science and Engineering Research Council (NSERC) Discovery Grant; NSERC Collaborative Research and Training Experience Vision Science and Applications Program; Alfred P. Sloan Foundation; Ontario Ministry for Research and Innovation Early Researcher Award; Canada Foundation for Innovation; Krembil Foundation; Brain Canada FX This work was supported by a National Science and Engineering Research Council (NSERC) Discovery Grant, the NSERC Collaborative Research and Training Experience Vision Science and Applications Program, the Alfred P. Sloan Foundation, an Ontario Ministry for Research and Innovation Early Researcher Award, the Canada Foundation for Innovation, the Krembil Foundation, and Brain Canada. NR 95 TC 7 Z9 7 U1 3 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 4 PY 2015 VL 35 IS 44 BP 14771 EP 14782 DI 10.1523/JNEUROSCI.0864-15.2015 PG 12 WC Neurosciences SC Neurosciences & Neurology GA CX9VN UT WOS:000366053900009 PM 26538648 ER PT J AU Karaca, E Harel, T Pehlivan, D Jhangiani, SN Gambin, T Akdemir, ZC Gonzaga-Jauregui, C Erdin, S Bayram, Y Campbell, IM Hunter, JV Atik, MM Van Esch, H Yuan, B Wiszniewski, W Isikay, S Yesil, G Yuregir, OO Bozdogan, ST Aslan, H Aydin, H Tos, T Aksoy, A De Vivo, DC Jain, P Geckinli, BB Sezer, O Gul, D Durmaz, B Cogulu, O Ozkinay, F Topcu, V Candan, S Cebi, AH Ikbal, M Gulec, EY Gezdirici, A Koparir, E Ekici, F Coskun, S Cicek, S Karaer, K Koparir, A Duz, MB Kirat, E Fenercioglu, E Ulucan, H Seven, M Guran, T Elcioglu, N Yildirim, MS Aktas, D Alikasifoglu, M Ture, M Yakut, T Overton, JD Yuksel, A Ozen, M Muzny, DM Adams, DR Boerwinkle, E Chung, WK Gibbs, RA Lupski, JR AF Karaca, Ender Harel, Tamar Pehlivan, Davut Jhangiani, Shalini N. Gambin, Tomasz Akdemir, Zeynep Coban Gonzaga-Jauregui, Claudia Erdin, Serkan Bayram, Yavuz Campbell, Ian M. Hunter, Jill V. Atik, Mehmed M. Van Esch, Hilde Yuan, Bo Wiszniewski, Wojciech Isikay, Sedat Yesil, Gozde Yuregir, Ozge O. Bozdogan, Sevcan Tug Aslan, Huseyin Aydin, Hatip Tos, Tulay Aksoy, Ayse De Vivo, Darryl C. Jain, Preti Geckinli, B. Bilge Sezer, Ozlem Gul, Davut Durmaz, Burak Cogulu, Ozgur Ozkinay, Ferda Topcu, Vehap Candan, Sukru Cebi, Alper Han Ikbal, Mevlit Gulec, Elif Yilmaz Gezdirici, Alper Koparir, Erkan Ekici, Fatma Coskun, Salih Cicek, Salih Karaer, Kadri Koparir, Asuman Duz, Mehmet Bugrahan Kirat, Emre Fenercioglu, Elif Ulucan, Hakan Seven, Mehmet Guran, Tulay Elcioglu, Nursel Yildirim, Mahmut Selman Aktas, Dilek Alikasifoglu, Mehmet Ture, Mehmet Yakut, Tahsin Overton, John D. Yuksel, Adnan Ozen, Mustafa Muzny, Donna M. Adams, David R. Boerwinkle, Eric Chung, Wendy K. Gibbs, Richard A. Lupski, James R. TI Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease SO NEURON LA English DT Article ID INTELLECTUAL-DISABILITY SYNDROME; CHROMATIN REMODELING COMPLEX; TRIPLE T COMPLEX; RNA HELICASES; PONTOCEREBELLAR HYPOPLASIA; ALZHEIMERS-DISEASE; SNX14 CAUSE; H-PRUNE; PROTEIN; MUTATIONS AB Development of the human nervous system involves complex interactions among fundamental cellular processes and requires a multitude of genes, many of which remain to be associated with human disease. We applied whole exome sequencing to 128 mostly consanguineous families with neurogenetic disorders that often included brain malformations. Rare variant analyses for both single nucleotide variant (SNV) and copy number variant (CNV) alleles allowed for identification of 45 novel variants in 43 known disease genes, 41 candidate genes, and CNVs in 10 families, with an overall potential molecular cause identified in >85% of families studied. Among the candidate genes identified, we found PRUNE, VARS, and DHX37 in multiple families and homozygous loss-of-function variants in AGBL2, SLC18A2, SMARCA1, UBQLN1, and CPLX1. Neuroimaging and in silico analysis of functional and expression proximity between candidate and known disease genes allowed for further understanding of genetic networks underlying specific types of brain malformations. C1 [Karaca, Ender; Harel, Tamar; Pehlivan, Davut; Jhangiani, Shalini N.; Gambin, Tomasz; Akdemir, Zeynep Coban; Bayram, Yavuz; Campbell, Ian M.; Atik, Mehmed M.; Yuan, Bo; Wiszniewski, Wojciech; Muzny, Donna M.; Gibbs, Richard A.; Lupski, James R.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Jhangiani, Shalini N.; Muzny, Donna M.; Boerwinkle, Eric; Gibbs, Richard A.; Lupski, James R.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Gonzaga-Jauregui, Claudia; Overton, John D.] Regeneron Pharmaceut Inc, Regeneron Genet Ctr, Tarrytown, NY 10591 USA. [Erdin, Serkan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Erdin, Serkan] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA. [Hunter, Jill V.] Texas Childrens Hosp, Dept Pediat Radiol, Houston, TX 77030 USA. [Van Esch, Hilde] Univ Hosp Leuven, Ctr Human Genet, B-3000 Louvain, Belgium. [Isikay, Sedat] Gaziantep Childrens Hosp, Dept Child Neurol, TR-27560 Gaziantep, Turkey. [Yesil, Gozde] Bezmialem Univ, Dept Med Genet, TR-34093 Istanbul, Turkey. [Yuregir, Ozge O.] Ankara Numune Training & Res Hosp, Dept Med Genet, TR-01240 Adana, Turkey. [Bozdogan, Sevcan Tug] Mersin Univ, Dept Med Genet, TR-33343 Mersin, Turkey. [Aslan, Huseyin] Eskisehir Osmangazi Univ, Fac Med, Dept Med Genet, TR-26480 Eskisehir, Turkey. [Aydin, Hatip] Namik Kemal Univ, Fac Med, Dept Med Genet, TR-59100 Tekirdag, Turkey. [Tos, Tulay] Sami Ulus Childrens Hosp, Dept Med Genet, TR-06080 Ankara, Turkey. [Aksoy, Ayse] Sami Ulus Childrens Hosp, Dept Pediat Neurol, TR-06080 Ankara, Turkey. [De Vivo, Darryl C.] Columbia Univ, Med Ctr, Dept Neurol, New York, NY 10032 USA. [Jain, Preti] Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, New York, NY 10032 USA. [Geckinli, B. Bilge] Marmara Univ, Sch Med, Dept Med Genet, TR-34722 Istanbul, Turkey. [Sezer, Ozlem] Samsun Educ & Res Hosp, Dept Med Genet, TR-55100 Samsun, Turkey. [Gul, Davut] Gulhane Mil Med Acad, Dept Med Genet, TR-06010 Ankara, Turkey. [Durmaz, Burak; Cogulu, Ozgur; Ozkinay, Ferda] Ege Univ, Fac Med, Dept Med Genet, TR-35040 Izmir, Turkey. [Topcu, Vehap] Zekai Tahir Burak Womens Hlth Training & Res Hosp, Dept Med Genet, TR-06230 Ankara, Turkey. [Candan, Sukru] Balikesir Ataturk Publ Hosp, Med Genet Sect, TR-10100 Balikesir, Turkey. [Cebi, Alper Han; Ikbal, Mevlit] Karadeniz Tech Univ, Dept Med Genet, TR-61310 Trabzon, Turkey. [Gulec, Elif Yilmaz; Gezdirici, Alper; Koparir, Erkan; Ekici, Fatma] Kanuni Sultan Suleyman Training & Res Hosp, Med Genet Sect, TR-34303 Istanbul, Turkey. [Coskun, Salih] Dicle Univ, Fac Med, Dept Med Genet, TR-21280 Diyarbakir, Turkey. [Cicek, Salih] Konya Numune Training & Res Hosp, Med Genet Sect, TR-42250 Konya, Turkey. [Karaer, Kadri] Intergen Genet Ctr, TR-06700 Ankara, Turkey. [Koparir, Asuman; Duz, Mehmet Bugrahan; Kirat, Emre; Fenercioglu, Elif; Ulucan, Hakan; Seven, Mehmet] Istanbul Univ, Cerrahpasa Med Sch, Dept Med Genet, TR-34098 Istanbul, Turkey. [Guran, Tulay] Marmara Univ Hosp, Dept Pediat Endocrinol & Diabet, TR-34899 Istanbul, Turkey. [Elcioglu, Nursel] Marmara Univ, Fac Med, Dept Pediat Genet, TR-34854 Istanbul, Turkey. [Yildirim, Mahmut Selman] Meram Med Fac, Necmettin Erbakan Univ, Dept Genet, TR-42060 Konya, Turkey. [Aktas, Dilek; Alikasifoglu, Mehmet] Hacettepe Univ, Sch Med, Damagen Genet Diagnost Ctr, TR-06230 Ankara, Turkey. [Aktas, Dilek; Alikasifoglu, Mehmet] Hacettepe Univ, Sch Med, Dept Med Genet, TR-06230 Ankara, Turkey. [Ture, Mehmet; Yakut, Tahsin] Uludag Univ, Fac Med, Dept Med Genet, TR-16120 Bursa, Turkey. [Yuksel, Adnan; Ozen, Mustafa] Biruni Univ, TR-34010 Istanbul, Turkey. [Adams, David R.] NIH, Off Director, Common Fund, Undiagnosed Dis Program, Bethesda, MD 20892 USA. [Boerwinkle, Eric] Univ Texas Houston, Hlth Sci Ctr, Ctr Human Genet, Houston, TX 77030 USA. [Chung, Wendy K.] Columbia Univ, Med Ctr, Dept Pediat & Med, New York, NY 10032 USA. [Lupski, James R.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Lupski, James R.] Texas Childrens Hosp, Houston, TX 77030 USA. RP Lupski, JR (reprint author), Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. EM jlupski@bcm.edu RI Erdin, Serkan/B-4988-2008; ikbal, mevlit/D-5880-2015; Bayram, Cem/D-7403-2013; AYDIN, Hatip/A-2711-2017; Topcu, Vehap/E-5545-2015; Topcu, Vehap/E-5545-2015; OI Erdin, Serkan/0000-0001-6587-2625; Bayram, Cem/0000-0001-8717-4668; Topcu, Vehap/0000-0001-6881-3284; Topcu, Vehap/0000-0001-7224-5697; Gonzaga-Jauregui, Claudia/0000-0002-4667-3679 FU U.S. National Human Genome Research Institute (NHGRI) NHLBI grant [U54HG006542]; NINDS [RO1 NS058529, K23NS078056]; NHGRI [5U54HG003273]; Medical Genetics Research Fellowship Program [T32 GM07526]; Regeneron FX We thank all the family members and collaborators who participated in this study. This work was supported by U.S. National Human Genome Research Institute (NHGRI) NHLBI grant U54HG006542 to the Baylor-Hopkins Center for Mendelian Genomics, NINDS grant RO1 NS058529 to J. R. L., and NHGRI 5U54HG003273 to R. A. G. T. H. is supported by the Medical Genetics Research Fellowship Program (T32 GM07526). W. W. is supported by Career Development Award K23NS078056 from NINDS. The authors would like to thank the ExAC and the groups that provided exome variant data for comparison. A full list of contributing groups can be found at http://exac.broadinstitute.org/about. J.R.L. has stock ownership in 23andMe and Lasergen and is a paid consultant for Regeneron. J. R. L. is also a coinventor on multiple United States and European patents related to molecular diagnostics for inherited neuropathies, eye diseases, and bacterial genomic fingerprinting. The Department of Molecular and Human Genetics at Baylor College of Medicine derives revenue from the chromosomal microarray analysis and clinical exome sequencing offered in the Medical Genetics Laboratory (https://www.bcm.edu/geneticlabs/). W. K. C. is a paid consultant for Regeneron and BioReference Laboratories. C.G.-J. and J. D. O. are employees of the RGC. NR 60 TC 17 Z9 17 U1 3 U2 19 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 EI 1097-4199 J9 NEURON JI Neuron PD NOV 4 PY 2015 VL 88 IS 3 BP 499 EP 513 DI 10.1016/j.neuron.2015.09.048 PG 15 WC Neurosciences SC Neurosciences & Neurology GA CX5TM UT WOS:000365765400011 PM 26539891 ER PT J AU Arsenault, D Coulombe, K Zhu, AJ Gong, CY Kil, KE Choi, JK Poutiainen, P Brownell, AL AF Arsenault, Dany Coulombe, Katherine Zhu, Aijun Gong, Chunyu Kil, Kun-Eek Choi, Ji-Kyung Poutiainen, Pekka Brownell, Anna-Liisa TI Loss of Metabotropic Glutamate Receptor 5 Function on Peripheral Benzodiazepine Receptor in Mice Prenatally Exposed to LPS SO PLOS ONE LA English DT Article ID POSITIVE ALLOSTERIC MODULATOR; MICROGLIAL ACTIVATION; MGLUR5 ANTAGONIST; RAT-BRAIN; PSYCHIATRIC-DISORDERS; MULTIPLE-SCLEROSIS; VIRAL-INFECTION; PROTEIN; SCHIZOPHRENIA; EXPRESSION AB Parental microglial induced neuroinflammation, triggered by bacterial-or viral infections, can induce neuropsychiatric disorders like schizophrenia and autism to offspring in animal models. Recent investigations suggest that microglia, the resident immune cells of the brain, provides a link between neurotransmission, immune cell activation, brain inflammation and neuronal dysfunction seen with the offspring. Relatively little is known about how reduction of brain inflammation and restoration of glial function are associated with diminution of brain degeneration and behavioral deficits in offspring. Increased mGluR5 expression and the long-lasting excitotoxic effects of the neurotoxin during brain development are associated with the glial dysfunctions. We investigated the relationship of mGluR5 and PBR and how they regulate glial function and inflammatory processes in mice prenatally exposed to LPS (120 mu g/kg, between gestational days 15 and 17), an inflammatory model of a psychiatric disorder. Using PET imaging, we showed that pharmacological activation of mGluR5 during 5 weeks reduced expression of classic inflammation marker PBR in many brain areas and that this molecular association was not present in LPS-exposed offspring. The post-mortem analysis revealed that the down regulation of PBR was mediated through activation of mGluR5 in astrocytes. In addition, we demonstrated that this interaction is defective in a mouse model of the psychiatric deficit offering a novel insight of mGluR5 involvement to brain related disorders and PBR related imaging studies. In conclusion, mGluR5 driven glutamatergic activity regulates astrocytic functions associated with PBR (cholesterol transport, neurosteroidogenesis, glial phenotype) during maturation and could be associated with neuropsychiatric disorders in offspring. C1 [Arsenault, Dany; Zhu, Aijun; Gong, Chunyu; Kil, Kun-Eek; Choi, Ji-Kyung; Poutiainen, Pekka; Brownell, Anna-Liisa] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging,Med Sch, Charlestown, MA 02129 USA. [Coulombe, Katherine] Univ Laval, Ctr Rech, CHU Quebec, Axe Neurosci Fac Pharm, Quebec City, PQ, Canada. RP Brownell, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging,Med Sch, Charlestown, MA 02129 USA. EM abrownell@partners.org FU National Institute of Mental Health [1R01MH091684]; Fonds de la Recherche en Sante du Quebec (FRSQ); Orion Farmos Research Foundation; Saastamoinen Foundation; Sigrid Juselius Foundation; Osk Huttunen Foundation; Kuopio University Foundation; National Center of Research Resources [S10RR029495, S10RR026666] FX This work was supported by the National Institute of Mental Health [grant 1R01MH091684]. Dany Arsenault was supported by scholarship from Fonds de la Recherche en Sante du Quebec (FRSQ). The authors would like to express their appreciation of the financial support for PP from The Orion Farmos Research Foundation, Saastamoinen Foundation, Sigrid Juselius Foundation, Osk Huttunen Foundation and Kuopio University Foundation. The used instrumentation in the experiments was supported by the grants from the National Center of Research Resources (grants S10RR029495 and S10RR026666]. NR 76 TC 1 Z9 1 U1 1 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 4 PY 2015 VL 10 IS 11 AR e0142093 DI 10.1371/journal.pone.0142093 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CV5GZ UT WOS:000364298400132 PM 26536027 ER PT J AU Liu, LL Li, F Pao, W Michor, F AF Liu, Lin L. Li, Fei Pao, William Michor, Franziska TI Dose-Dependent Mutation Rates Determine Optimum Erlotinib Dosing Strategies for EGFR Mutant Non-Small Cell Lung Cancer Patients SO PLOS ONE LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; DRUG-INDUCED APOPTOSIS; COMBINATION CHEMOTHERAPY; MATHEMATICAL-MODEL; TARGETED THERAPIES; CLONAL EXPANSION; STOCHASTIC-MODEL; BREAST-CANCER; TUMOR-GROWTH; RESISTANCE AB Background The advent of targeted therapy for cancer treatment has brought about a paradigm shift in the clinical management of human malignancies. Agents such as erlotinib used for EGFR-mutant non-small cell lung cancer or imatinib for chronic myeloid leukemia, for instance, lead to rapid tumor responses. Unfortunately, however, resistance often emerges and renders these agents ineffective after a variable amount of time. The FDA-approved dosing schedules for these drugs were not designed to optimally prevent the emergence of resistance. To this end, we have previously utilized evolutionary mathematical modeling of treatment responses to elucidate the dosing schedules best able to prevent or delay the onset of resistance. Here we expand on our approaches by taking into account dose-dependent mutation rates at which resistant cells emerge. The relationship between the serum drug concentration and the rate at which resistance mutations arise can lead to non-intuitive results about the best dose administration strategies to prevent or delay the emergence of resistance. Methods We used mathematical modeling, available clinical trial data, and different considerations of the relationship between mutation rate and drug concentration to predict the effectiveness of different dosing strategies. Results We designed several distinct measures to interrogate the effects of different treatment dosing strategies and found that a low-dose continuous strategy coupled with high-dose pulses leads to the maximal delay until clinically observable resistance. Furthermore, the response to treatment is robust against different assumptions of the mutation rate as a function of drug concentration. Conclusions For new and existing targeted drugs, our methodology can be employed to compare the effectiveness of different dose administration schedules and investigate the influence of changing mutation rates on outcomes. C1 [Liu, Lin L.; Li, Fei; Michor, Franziska] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Liu, Lin L.; Michor, Franziska] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Pao, William] Vanderbilt Ingram Canc Ctr, Nashville, TN 27232 USA. RP Michor, F (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. EM michor@jimmy.harvard.edu FU Dana-Farber Cancer Institute Physical Sciences-Oncology Center [NCI U54CA143798]; US National Cancer Institute [R01CA121210, P01CA129243] FX The authors acknowledge support from the Dana-Farber Cancer Institute Physical Sciences-Oncology Center (NCI U54CA143798) and from US National Cancer Institute grants R01CA121210 and P01CA129243. NR 51 TC 1 Z9 1 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 4 PY 2015 VL 10 IS 11 AR e0141665 DI 10.1371/journal.pone.0141665 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CV5GZ UT WOS:000364298400075 PM 26536620 ER PT J AU Jena, AB Schoemaker, L Bhattacharya, J Seabury, SA AF Jena, Anupam B. Schoemaker, Lena Bhattacharya, Jay Seabury, Seth A. TI Physician spending and subsequent risk of malpractice claims: observational study SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Article ID DEFENSIVE MEDICINE PRACTICES; ADVERSE EVENTS; DIAGNOSTIC ERROR; CESAREAN-SECTION; NATIONAL-SURVEY; LIABILITY; CARE; LITIGATION; DOCTORS; MORTALITY AB STUDY QUESTION Is a higher use of resources by physicians associated with a reduced risk of malpractice claims? METHODS Using data on nearly all admissions to acute care hospitals in Florida during 2000-09 linked to malpractice history of the attending physician, this study investigated whether physicians in seven specialties with higher average hospital charges in a year were less likely to face an allegation of malpractice in the following year, adjusting for patient characteristics, comorbidities, and diagnosis. To provide clinical context, the study focused on obstetrics, where the choice of caesarean deliveries are suggested to be influenced by defensive medicine, and whether obstetricians with higher adjusted caesarean rates in a year had fewer alleged malpractice incidents the following year. STUDY ANSWER AND LIMITATIONS The data included 24 637 physicians, 154 725 physician years, and 18 352 391 hospital admissions; 4342 malpractice claims were made against physicians (2.8% per physician year). Across specialties, greater average spending by physicians was associated with reduced risk of incurring a malpractice claim. For example, among internists, the probability of experiencing an alleged malpractice incident in the following year ranged from 1.5% (95% confidence interval 1.2% to 1.7%) in the bottom spending fifth ($ 19 725 (12 pound 800; (sic)17 400) per hospital admission) to 0.3% (0.2% to 0.5%) in the top fifth ($39 379 per hospital admission). In six of the specialties, a greater use of resources was associated with statistically significantly lower subsequent rates of alleged malpractice incidents. A principal limitation of this study is that information on illness severity was lacking. It is also uncertain whether higher spending is defensively motivated. WHAT THIS STUDY ADDS Within specialty and after adjustment for patient characteristics, higher resource use by physicians is associated with fewer malpractice claims. C1 [Jena, Anupam B.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Jena, Anupam B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jena, Anupam B.; Bhattacharya, Jay; Seabury, Seth A.] Natl Bur Econ Res, Cambridge, MA 02138 USA. [Schoemaker, Lena; Bhattacharya, Jay] Stanford Univ, Sch Med, Ctr Primary Care & Outcomes Res, Stanford, CA 94305 USA. [Seabury, Seth A.] Univ So Calif, Dept Emergency Med, Los Angeles, CA USA. [Seabury, Seth A.] Univ So Calif, Leonard D Schaeffer Ctr Hlth Policy & Econ, Los Angeles, CA USA. RP Jena, AB (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. EM jena@hcp.med.harvard.edu FU Office of the Director, National Institutes of Health (NIH early independence award) [1DP5OD017897-01]; National Institute of Aging [R37 AG036791] FX This study was supported by the Office of the Director, National Institutes of Health (NIH early independence award, grant 1DP5OD017897-01 to ABJ) and National Institute of Aging (R37 AG036791 to JB). NR 59 TC 8 Z9 8 U1 3 U2 4 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BMJ-BRIT MED J JI BMJ-British Medical Journal PD NOV 4 PY 2015 VL 351 AR h5516 DI 10.1136/bmj.h5516 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CV6OS UT WOS:000364390100005 PM 26538498 ER PT J AU Goel, A Maski, MR Bajracharya, S Wenger, JB Zhang, DS Salahuddin, S Shahul, SS Thadhani, R Seely, EW Karumanchi, SA Rana, S AF Goel, Arvind Maski, Manish R. Bajracharya, Surichhya Wenger, Julia B. Zhang, Dongsheng Salahuddin, Saira Shahul, Sajid S. Thadhani, Ravi Seely, Ellen W. Karumanchi, S. Ananth Rana, Sarosh TI Epidemiology and Mechanisms of De Novo and Persistent Hypertension in the Postpartum Period SO CIRCULATION LA English DT Article DE angiogenesis; hypertension; postpartum; pre-eclampsia; pregnancy; receptors, vascular endothelial growth factor ID ANGIOGENIC FACTORS; GESTATIONAL HYPERTENSION; SOLUBLE ENDOGLIN; BLOOD-PRESSURE; PREECLAMPSIA; RISK; PREGNANCY; MANAGEMENT; ECLAMPSIA; WOMEN AB Background-The pathophysiology of hypertension in the immediate postpartum period is unclear. Methods and Results-We studied 988 consecutive women admitted to a tertiary medical center for cesarean section of a singleton pregnancy. The angiogenic factors soluble fms-like tyrosine kinase 1 and placental growth factor, both biomarkers associated with preeclampsia, were measured on antepartum blood samples. We then performed multivariable analyses to determine factors associated with the risk of developing postpartum hypertension. Of the 988 women, 184 women (18.6%) developed postpartum hypertension. Of the 184 women, 77 developed de novo hypertension in the postpartum period, and the remainder had a hypertensive disorder of pregnancy in the antepartum period. A higher body mass index and history of diabetes mellitus were associated with the development of postpartum hypertension. The antepartum ratio of soluble fms-like tyrosine kinase 1 to placental growth factor positively correlated with blood pressures in the postpartum period (highest postpartum systolic blood pressure [r=0.29, P<0.001] and diastolic blood pressure [r=0.28, P<0.001]). Moreover, the highest tertile of the antepartum ratio of soluble fms-like tyrosine kinase 1 to placental growth factor was independently associated with postpartum hypertension (de novo hypertensive group: odds ratio, 2.25; 95% confidence interval, 1.19-4.25; P=0.01; in the persistent hypertensive group: odds ratio, 2.61; 95% confidence interval, 1.12-6.05; P=0.02) in multivariable analysis. Women developing postpartum hypertension had longer hospitalizations than those who remained normotensive (6.5 +/- 3.5 versus 5.7 +/- 3.4 days; P<0.001). Conclusions-Hypertension in the postpartum period is relatively common and is associated with prolonged hospitalization. Women with postpartum hypertension have clinical risk factors and an antepartum plasma angiogenic profile similar to those found in women with preeclampsia. These data suggest that women with postpartum hypertension may represent a group of women with subclinical or unresolved preeclampsia. C1 [Goel, Arvind; Maski, Manish R.; Zhang, Dongsheng; Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Dept Med, Div Nephrol, Boston, MA 02215 USA. [Bajracharya, Surichhya; Salahuddin, Saira; Karumanchi, S. Ananth; Rana, Sarosh] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02215 USA. [Shahul, Sajid S.] Beth Israel Deaconess Med Ctr, Dept Anesthesiol, Div Crit Care, Boston, MA 02215 USA. [Wenger, Julia B.; Thadhani, Ravi; Seely, Ellen W.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Wenger, Julia B.; Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Seely, Ellen W.] Brigham & Womens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. [Karumanchi, S. Ananth] Howard Hughes Med Inst, Boston, MA 02115 USA. [Rana, Sarosh] Univ Chicago, Dept Obstet & Gynecol, Sect Maternal Fetal Med, Chicago, IL 60637 USA. RP Karumanchi, SA (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave,RN 370D, Boston, MA 02215 USA. EM sananth@bidmc.harvard.edu; srana2@bsd.uchicago.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [K24]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [KO8]; National Heart, Lung, and Blood Institute [R56] FX Dr Thadhani is supported by a K24 award from National Institute of Diabetes and Digestive and Kidney Diseases. Dr Karumanchi is an investigator of the Howard Hughes Medical Institute. Dr Rana is supported by a KO8 award from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr Seely is supported by an R56 award from the National Heart, Lung, and Blood Institute. NR 22 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 3 PY 2015 VL 132 IS 18 BP 1726 EP 1733 DI 10.1161/CIRCULATIONAHA.115.015721 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DJ9PP UT WOS:000374545700014 PM 26416810 ER PT J AU Smith, CS Gerrish, WG Nash, M Fisher, A Brotman, A Smith, D Student, A Green, M Donovan, J Dreffin, M AF Smith, C. Scott Gerrish, Winslow G. Nash, Melanie Fisher, Amber Brotman, Adam Smith, Deborah Student, Ami Green, Melissa Donovan, Jodie Dreffin, Melissa TI Professional equipoise: Getting beyond dominant discourses in an interprofessional team SO JOURNAL OF INTERPROFESSIONAL CARE LA English DT Article DE Education; interprofessional education; interprofessional relations; interprofessional research; qualitative method ID CLINICAL-PSYCHOLOGY; PRIMARY-CARE; EDUCATION; COLLABORATION; PHARMACISTS; AMERICA AB In 2011, the US Department of Veterans Affairs established five Centers of Excellence to study training in the patient-centered medical home clinical microsystem. Early on, our center began a discourse analysis in order to better understand each profession's assumptions about roles, responsibilities, and the basis for truth in clinical care. We discovered that these different discourses were pervasive and led to unhelpful stereotypes of each other. This article describes the evidence we identified that led us to hypothesize these conflicting discourses and stereotypes. Specifically, we report on our attempts to identify the traditional discourses of four post-graduate professionsmedicine, nurse practitioner, psychology, and pharmacy. We also share lessons from our efforts to defuse participants from their identified discursive assumptions, and develop appreciation and value for the discursive contributions of other professionsa process we call professional equipoise. We conclude that we can change these discourses and the professional identity formation of novices if we provide sustained, integrated interprofessional education curriculum. This implies that we need: embedded, longitudinal training; faculty role modeling of inquisitiveness, respectful relationships, and risk taking; and safe and honest discussion about our differences. C1 [Smith, C. Scott; Nash, Melanie; Fisher, Amber; Brotman, Adam; Donovan, Jodie; Dreffin, Melissa] Boise VA Med Ctr, Boise, ID 83702 USA. [Gerrish, Winslow G.] Family Med Residency Idaho, Boise, ID USA. [Smith, Deborah] Gonzaga Univ, Dept Nursing, Spokane, WA 99258 USA. [Student, Ami] San Francisco VA Med Ctr, San Francisco, CA USA. [Green, Melissa] Salt Lake City VA, Salt Lake City, UT USA. RP Smith, CS (reprint author), Boise VA Med Ctr, 500 W Ft St, Boise, ID 83702 USA. EM scott.smith2@va.gov NR 42 TC 0 Z9 0 U1 2 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1356-1820 EI 1469-9567 J9 J INTERPROF CARE JI J. Interprofessional Care PD NOV 3 PY 2015 VL 29 IS 6 BP 603 EP 609 DI 10.3109/13561820.2015.1051216 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CY5LX UT WOS:000366450200015 PM 26652633 ER PT J AU Zhang, W Levi, L Banerjee, P Jain, M Noy, N AF Zhang, Wei Levi, Liraz Banerjee, Pallab Jain, Mukesh Noy, Noa TI Kruppel-like factor 2 suppresses mammary carcinoma growth by regulating retinoic acid signaling SO ONCOTARGET LA English DT Article DE Kruppel-like factor; nuclear receptors; retinoic acid; vitamin A; breast cancer ID BINDING PROTEIN-II; ACTIVATED RECEPTOR-BETA/DELTA; HUMAN COLON-CANCER; CELL-GROWTH; PPAR-BETA/DELTA; TRANSCRIPTION FACTORS; INTERACTION DOMAIN; GENE-EXPRESSION; RAR AGONISTS; IN-VITRO AB The transcription factor Kruppel-like factor 2 (KLF2) displays anticarcinogenic activities but the mechanism that underlies this activity is unknown. We show here that KLF2 is markedly downregulated in human breast cancers and that its expression positively correlates with breast cancer patient survival. We show further that KLF2 suppresses tumor development by controlling the transcriptional activity of the vitamin A metabolite retinoic acid (RA). RA regulates gene transcription by activating two types of nuclear receptors: RA receptors (RARs), which inhibit tumor development, and peroxisome proliferator-activated receptor beta/delta (PPAR beta/delta), which promotes tumorigenesis. The partitioning of RA between these receptors is regulated by two carrier proteins: cellular retinoic acid-binding protein 2 (CRABP2), which delivers RA to RARs, and fatty acid-binding protein 5 (FABP5), which shuttles ligands to PPAR beta/delta. We show that KLF2 induces the expression of CRABP2 and RAR gamma and inhibits the expression FABP5 and PPAR beta/delta thereby shifting RA signaling from the pro-carcinogenic FABP5/PPAR beta/delta to the growth-suppressing CRABP2/RAR path. The data thus reveal that KLF2 suppresses tumor growth by controlling the transcriptional activities of RA. C1 [Zhang, Wei; Levi, Liraz; Noy, Noa] Cleveland Clin Fdn, Dept Cellular & Mol Med, Lerner Res Inst, Cleveland, OH 44195 USA. [Banerjee, Pallab] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jain, Mukesh] Case Western Reserve Univ, Sch Med, Case Cardiovasc Res Inst, Cleveland, OH USA. [Noy, Noa] Case Western Reserve Univ, Sch Med, Dept Nutr, Cleveland, OH USA. RP Noy, N (reprint author), Cleveland Clin Fdn, Dept Cellular & Mol Med, Lerner Res Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM noyn@ccf.org RI Zhang, Wei/G-8229-2016; OI Levi, Liraz/0000-0001-7462-2396 FU NIDDK NIH HHS [R01 DK060684, R01-DK060684, R01-DK088669] NR 49 TC 3 Z9 3 U1 0 U2 1 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD NOV 3 PY 2015 VL 6 IS 34 BP 35830 EP 35842 DI 10.18632/oncotarget.5767 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CY0QZ UT WOS:000366111900063 PM 26416422 ER PT J AU Low, D Subramaniam, R Lin, L Aomatsu, T Mizoguchi, A Ng, A DeGruttola, AK Lee, CG Elias, JA Andoh, A Mino-Kenudson, M Mizoguchi, E AF Low, Daren Subramaniam, Renuka Lin, Li Aomatsu, Tomoki Mizoguchi, Atsushi Ng, Aylwin DeGruttola, Arianna K. Lee, Chun Geun Elias, Jack A. Andoh, Akira Mino-Kenudson, Mari Mizoguchi, Emiko TI Chitinase 3-like 1 induces survival and proliferation of intestinal epithelial cells during chronic inflammation and colitis-associated cancer by regulating S100A9 SO ONCOTARGET LA English DT Article DE mammalian chitinase; colitis-associated cancer; bone marrow chimeras; RAGE; intestinal epithelial cells ID COLORECTAL-CANCER; TISSUE RESPONSES; PROTEINS; CALPROTECTIN; APOPTOSIS; EXPRESSION; MECHANISM; PATHWAY; INJURY; MICE AB Many host-factors are inducibly expressed during the development of inflammatory bowel disease (IBD), each having their unique properties, such as immune activation, bacterial clearance, and tissue repair/remodeling. Dysregulation/imbalance of these factors may have pathogenic effects that can contribute to colitis-associated cancer (CAC). Previous reports showed that IBD patients inducibly express colonic chitinase 3-like 1 (CHI3L1) that is further upregulated during CAC development. However, little is known about the direct pathogenic involvement of CHI3L1 in vivo. Here we demonstrate that CHI3L1 (aka Brp39) knockout (KO) mice treated with azoxymethane (AOM)/dextran sulphate sodium (DSS) developed severe colitis but lesser incidence of CAC as compared to that in wild-type (WT) mice. Highest CHI3L1 expression was found during the chronic phase of colitis, rather than the acute phase, and is essential to promote intestinal epithelial cell (IEC) proliferation in vivo. This CHI3L1-mediated cell proliferation/survival involves partial downregulation of the pro-apoptotic S100A9 protein that is highly expressed during the acute phase of colitis, by binding to the S100A9 receptor, RAGE (Receptor for Advanced Glycation End products). This interaction disrupts the S100A9-associated expression positive feedback loop during early immune activation, creating a CHI3L1(hi) S100A9(low) colonic environment, especially in the later phase of colitis, which promotes cell proliferation/survival of both normal IECs and tumor cells. C1 [Low, Daren; Subramaniam, Renuka; Ng, Aylwin; DeGruttola, Arianna K.; Mizoguchi, Emiko] Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. [Low, Daren; Subramaniam, Renuka; Ng, Aylwin; DeGruttola, Arianna K.; Mino-Kenudson, Mari; Mizoguchi, Emiko] Harvard Univ, Sch Med, Boston, MA USA. [Lin, Li] NIA, Lab Cardiovasc Sci, NIH, Baltimore, MD 21224 USA. [Aomatsu, Tomoki; Andoh, Akira] Shiga Univ Med Sci, Grad Sch, Div Mucosal Immunol, Otsu, Shiga 52021, Japan. [Mizoguchi, Atsushi] Kurume Univ, Sch Med, Dept Immunol, Kurume, Fukuoka 830, Japan. [Lee, Chun Geun; Elias, Jack A.] Brown Univ, Warren Alpert Sch Med, Dept Microbiol & Immunol, Providence, RI 02912 USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Mizoguchi, Emiko] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. RP Mizoguchi, E (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. EM emizoguchi@mgh.harvard.edu FU Intramural NIH HHS; NIAID NIH HHS [R01 AI081807, AI81807]; NIDDK NIH HHS [R01 DK091247, DK91247, R01 DK080070, R01-DK80070] NR 34 TC 7 Z9 8 U1 1 U2 2 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD NOV 3 PY 2015 VL 6 IS 34 BP 36535 EP 36550 DI 10.18632/oncotarget.5440 PG 16 WC Oncology; Cell Biology SC Oncology; Cell Biology GA CY0QZ UT WOS:000366111900113 PM 26431492 ER PT J AU Raja, AS Greenberg, JO Qaseem, A Denberg, TD Fitterman, N Schuur, JD AF Raja, Ali S. Greenberg, Jeffrey O. Qaseem, Amir Denberg, Thomas D. Fitterman, Nick Schuur, Jeremiah D. CA Clinical Guidelines Comm Amer Coll TI Evaluation of Patients With Suspected Acute Pulmonary Embolism: Best Practice Advice From the Clinical Guidelines Committee of the American College of Physicians SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID RULE-OUT CRITERIA; DEEP VENOUS THROMBOSIS; EMERGENCY-DEPARTMENT PATIENTS; ENHANCED COMPUTED-TOMOGRAPHY; CONTRAST-INDUCED NEPHROPATHY; D-DIMER ASSAY; DECISION-SUPPORT; PRETEST PROBABILITY; RANDOMIZED-TRIAL; RADIATION-EXPOSURE AB Description: Pulmonary embolism (PE) can be a severe disease and is difficult to diagnose, given its nonspecific signs and symptoms. Because of this, testing patients with suspected acute PE has increased dramatically. However, the overuse of some tests, particularly computed tomography (CT) and plasma D-dimer measurement, may not improve care while potentially leading to patient harm and unnecessary expense. Methods: The literature search encompassed studies indexed by MEDLINE (1966-2014; English-language only) and included all clinical trials and meta-analyses on diagnostic strategies, decision rules, laboratory tests, and imaging studies for the diagnosis of PE. This document is not based on a formal systematic review, but instead seeks to provide practical advice based on the best available evidence and recent guidelines. The target audience for this paper is all clinicians; the target patient population is all adults, both inpatient and outpatient, suspected of having acute PE. Best Practice Advice 1: Clinicians should use validated clinical prediction rules to estimate pretest probability in patients in whom acute PE is being considered. Best Practice Advice 2: Clinicians should not obtain D-dimer measurements or imaging studies in patients with a low pretest probability of PE and who meet all Pulmonary Embolism Rule-Out Criteria. Best Practice Advice 3: Clinicians should obtain a high-sensitivity D-dimer measurement as the initial diagnostic test in patients who have an intermediate pretest probability of PE or in patients with low pretest probability of PE who do not meet all Pulmonary Embolism Rule-Out Criteria. Clinicians should not use imaging studies as the initial test in patients who have a low or intermediate pretest probability of PE. Best Practice Advice 4: Clinicians should use age-adjusted D-dimer thresholds (age x 10 ng/mL rather than a generic 500 ng/mL) in patients older than 50 years to determine whether imaging is warranted. Best Practice Advice 5: Clinicians should not obtain any imaging studies in patients with a D-dimer level below the age-adjusted cutoff. Best Practice Advice 6: Clinicians should obtain imaging with CT pulmonary angiography (CTPA) in patients with high pretest probability of PE. Clinicians should reserve ventilation-perfusion scans for patients who have a contraindication to CTPA or if CTPA is not available. Clinicians should not obtain a D-dimer measurement in patients with a high pretest probability of PE. C1 [Raja, Ali S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Greenberg, Jeffrey O.; Schuur, Jeremiah D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Qaseem, Amir] Amer Coll Physicians, Philadelphia, PA 19106 USA. [Fitterman, Nick] Hofstra North Shore Long Isl Jewish Sch Med, Huntington, NY 11743 USA. [Denberg, Thomas D.] Caril Clin, Roanoke, VA 24036 USA. RP Qaseem, A (reprint author), Amer Coll Physicians, 190 N Independence Mall West, Philadelphia, PA 19106 USA. FU ACP operating budget FX Financial support for the development of this paper comes exclusively from the ACP operating budget. NR 85 TC 21 Z9 23 U1 0 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 3 PY 2015 VL 163 IS 9 BP 701 EP + DI 10.7326/M14-1772 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA CX3PF UT WOS:000365610600007 PM 26414967 ER PT J AU Grover, S Raesima, M Bvochora-Nsingo, M Chiyapo, SP Balang, D Tapela, N Balogun, O Kayembe, MKA Russell, AH Monare, B Tanyala, S Bhat, J Thipe, K Nchunga, M Mayisela, S Kizito, B Ho-Foster, A Gaolebale, BE Gaolebale, PA Efstathiou, JA Dryden-Peterson, S Zetola, N Hahn, SM Robertson, ES Lin, LL Morroni, C Ramogola-Masire, D AF Grover, Surbhi Raesima, Mmakgomo Bvochora-Nsingo, Memory Chiyapo, Sebathu P. Balang, Dawn Tapela, Neo Balogun, Onyinye Kayembe, Mukendi K. A. Russell, Anthony H. Monare, Barati Tanyala, Senate Bhat, Jailakshmi Thipe, Kealeboga Nchunga, Metlha Mayisela, Susan Kizito, Balladiah Ho-Foster, Ari Gaolebale, Babe Eunice Gaolebale, Ponatshego A. Efstathiou, Jason A. Dryden-Peterson, Scott Zetola, Nicola Hahn, Stephen M. Robertson, Erle S. Lin, Lilie L. Morroni, Chelsea Ramogola-Masire, Doreen TI Cervical cancer in Botswana: current state and future steps for screening and treatment programs SO FRONTIERS IN ONCOLOGY LA English DT Review DE cervical cancer; Botswana; cancer screening; cancer treatment; HIV and cancer ID LOW-RESOURCE SETTINGS; DEVELOPING-COUNTRIES; COST-EFFECTIVENESS; SEE; PREVENTION; STRATEGIES; BENEFITS; BURDEN; TRIAL AB Botswana has a high burden of cervical cancer due to a limited screening program and high HIV prevalence. About 60% of the cervical cancer patients are HIV positive; most present with advanced cervical disease. Through initiatives by the Botswana Ministry of Health and various strategic partnerships, strides have been made in treatment of pre-invasive and invasive cancer. The See and Treat program for cervical cancer is expanding throughout the country. Starting in 2015, school-going girls will be vaccinated against HPV. In regards to treatment of invasive cancer, a multidisciplinary clinic has been initiated at the main oncology hospital to streamline care. However, challenges remain such as delays in treatment, lack of trained human personnel, limited follow-up care, and little patient education. Despite improvements in the care of pre-invasive and invasive cervical cancer patients, for declines in cervical cancer-related morbidity and mortality to be achieved, Botswana needs to continue to invest in decreasing the burden of disease and improving patient outcomes of patients with cervical cancer. C1 [Grover, Surbhi; Zetola, Nicola; Lin, Lilie L.] Univ Penn, Dept Radiat Oncol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Grover, Surbhi; Monare, Barati; Tanyala, Senate; Bhat, Jailakshmi; Thipe, Kealeboga; Nchunga, Metlha; Mayisela, Susan; Kizito, Balladiah; Ho-Foster, Ari; Morroni, Chelsea; Ramogola-Masire, Doreen] Botswana Univ Penn Partnership, Gaborone, Botswana. [Raesima, Mmakgomo] Minist Hlth, Natl Cerv Canc Prevent Programme, Gaborone, Botswana. [Bvochora-Nsingo, Memory; Balang, Dawn] Gaborone Private Hosp, Dept Oncol, Gaborone, Botswana. [Chiyapo, Sebathu P.; Tapela, Neo; Gaolebale, Babe Eunice; Gaolebale, Ponatshego A.] Princess Marina Hosp, Gaborone, Botswana. [Tapela, Neo] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. [Balogun, Onyinye] NYU, Dept Radiat Oncol, Perlmutter Canc Ctr, New York, NY USA. [Kayembe, Mukendi K. A.] Natl Hlth Lab, Gaborone, Botswana. [Russell, Anthony H.; Efstathiou, Jason A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Ho-Foster, Ari; Morroni, Chelsea] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Dryden-Peterson, Scott] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Hahn, Stephen M.] Univ Texas MD Anderson Canc Ctr, Div Radiat Oncol, Houston, TX 77030 USA. [Robertson, Erle S.] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Morroni, Chelsea] Univ Botswana, Sch Med, Gaborone, Botswana. [Morroni, Chelsea] UCL, Inst Womens Hlth, London, England. [Morroni, Chelsea] UCL, Inst Global Hlth, London, England. [Ramogola-Masire, Doreen] Univ Penn, Dept Obstet & Gynecol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Ramogola-Masire, Doreen] Univ Botswana, Fac Med, Dept Obstet & Gynecol, Gaborone, Botswana. RP Grover, S (reprint author), Univ Penn, Dept Radiat Oncol, Perelman Sch Med, Philadelphia, PA 19104 USA. EM surbhi.grover@uphs.upenn.edu FU NIAID NIH HHS [P30 AI045008, K23 AI091434] NR 21 TC 3 Z9 3 U1 1 U2 2 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 2234-943X J9 FRONT ONCOL JI Front. Oncol. PD NOV 3 PY 2015 VL 5 AR 239 DI 10.3389/fonc.2015.00239 PG 5 WC Oncology SC Oncology GA CX6KC UT WOS:000365808600001 PM 26579491 ER PT J AU Knoechel, B Aster, JC AF Knoechel, Birgit Aster, Jon C. TI Metabolic Mechanisms of Drug Resistance in Leukemia SO CELL METABOLISM LA English DT Editorial Material ID ACUTE LYMPHOBLASTIC-LEUKEMIA; C-MYC; NOTCH1; CANCER AB Tumor cells frequently undergo metabolic reprogramming, but it is unknown how these metabolic changes relate to drug resistance. A recent article now demonstrates that PI3K/AKT signaling causes a metabolic switch from glutaminolysis to aerobic glycolysis in Notch-dependent T cell acute lymphoblastic leukemia (T-ALL). C1 [Knoechel, Birgit] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Knoechel, Birgit; Aster, Jon C.] Harvard Univ, Med Ctr, Boston, MA 02115 USA. [Knoechel, Birgit; Aster, Jon C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Aster, Jon C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Aster, JC (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM jaster@partners.org FU NCI NIH HHS [K08 CA191091] NR 9 TC 0 Z9 0 U1 2 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 EI 1932-7420 J9 CELL METAB JI Cell Metab. PD NOV 3 PY 2015 VL 22 IS 5 BP 759 EP 760 DI 10.1016/j.cmet.2015.10.005 PG 2 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA CW7QJ UT WOS:000365193900004 PM 26536486 ER PT J AU Bohr, S Patel, SJ Vasko, R Shen, KY Golberg, A Berthiaume, F Yarmush, ML AF Bohr, Stefan Patel, Suraj J. Vasko, Radovan Shen, Keyue Golberg, Alexander Berthiaume, Francois Yarmush, Martin L. TI The Role of CHI3L1 (Chitinase-3-Like-1) in the Pathogenesis of Infections in Burns in a Mouse Model SO PLOS ONE LA English DT Article ID COLONIC EPITHELIAL-CELLS; CHITIN-BINDING PROTEINS; INFLAMMATORY-BOWEL-DISEASE; NECROSIS-FACTOR-ALPHA; PSEUDOMONAS-AERUGINOSA; GENE-EXPRESSION; SERUM YKL-40; INTESTINAL INFLAMMATION; RHEUMATOID-ARTHRITIS; BACTERIAL ADHESION AB In severe burn injury the unique setting of a depleted, dysfunctional immune system along with a loss of barrier function commonly results in opportunistic infections that eventually proof fatal. Unfortunately, the dynamic sequence of bacterial contamination, colonization and eventually septic invasion with bacteria such as Pseudomonas species is still poorly understood although a limiting factor in clinical decision making. Increasing evidence supports the notion that inhibition of bacterial translocation into the wound site may be an effective alternative to prevent infection. In this context we investigated the role of the mammalian Chitinase-3-Like-1 (CHI3L1) non-enyzmatic protein predominately expressed on epithelial as well as innate immune cells as a potential bacterial-translocation-mediating factor. We show a strong trend that a modulation of chitinase expression is likely to be effective in reducing mortality rates in a mouse model of burn injury with superinfection with the opportunistic PA14 Pseudomonas strain, thus demonstrating possible clinical leverage. C1 [Bohr, Stefan; Patel, Suraj J.; Shen, Keyue; Golberg, Alexander; Yarmush, Martin L.] Harvard Univ, Sch Med, Shriners Hosp Children, Ctr Engn Med, Boston, MA 02138 USA. [Bohr, Stefan; Patel, Suraj J.; Shen, Keyue; Golberg, Alexander; Yarmush, Martin L.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Vasko, Radovan] New York Med Coll, Dept Med, Valhalla, NY 10595 USA. [Berthiaume, Francois; Yarmush, Martin L.] Rutgers State Univ, Dept Biomed Engn, New Brunswick, NJ USA. [Bohr, Stefan] Rhein Westfal TH Aachen, UKA Univ Clin, Dept Plast & Hand Surg, Burn Ctr, D-52062 Aachen, Germany. [Vasko, Radovan] UMG Univ Clin, Dept Nephrol & Rheumatol, Gottingen, Germany. [Golberg, Alexander] Tel Aviv Univ, Porter Sch Environm Studies, IL-69978 Tel Aviv, Israel. RP Bohr, S (reprint author), Harvard Univ, Sch Med, Shriners Hosp Children, Ctr Engn Med, Boston, MA 02138 USA. EM sbohr@ukaachen.de FU Shriners Hospitals for Children; Deutsche Forschungs Gemeinschaft (DFG, Germany) postdoctoral fellowship award [GZ:BO3468/2-1] FX This work was funded by the Shriners Hospitals for Children, https://www.shrinershospitalsforchildren.org/locations/boston. SB is a receipt of a Deutsche Forschungs Gemeinschaft (DFG, Germany) postdoctoral fellowship award (GZ:BO3468/2-1), http://www.dfg.de/en/. NR 67 TC 2 Z9 2 U1 3 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 3 PY 2015 VL 10 IS 11 AR e0140440 DI 10.1371/journal.pone.0140440 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CV1QH UT WOS:000364032600006 PM 26528713 ER PT J AU Chung, YG Seth, A Doyle, C Franck, D Kim, D Cristofaro, V Benowitz, LI Tu, DD Estrada, CR Mauney, JR Sullivan, MP Adam, RM AF Chung, Yeun Goo Seth, Abhishek Doyle, Claire Franck, Debra Kim, Daniel Cristofaro, Vivian Benowitz, Larry I. Tu, Duong D. Estrada, Carlos R. Mauney, Joshua R. Sullivan, Maryrose P. Adam, Rosalyn M. TI Inosine Improves Neurogenic Detrusor Overactivity following Spinal Cord Injury SO PLOS ONE LA English DT Article ID RETINAL GANGLION-CELLS; PURINE-SENSITIVE MECHANISM; ADENOSINE RECEPTORS; PROMOTES RECOVERY; AFFERENT ACTIVITY; BRAIN-INJURY; AXON GROWTH; BLADDER; RATS; MODEL AB Neurogenic detrusor overactivity and the associated loss of bladder control are among the most challenging complications of spinal cord injury (SCI). Anticholinergic agents are the mainstay for medical treatment of detrusor overactivity. However, their use is limited by significant side effects such that a search for new treatments is warranted. Inosine is a naturally occurring purine nucleoside with neuroprotective, neurotrophic and antioxidant effects that is known to improve motor function in preclinical models of SCI. However, its effect on lower urinary tract function has not been determined. The objectives of this study were to determine the effect of systemic administration of inosine on voiding function following SCI and to delineate potential mechanisms of action. Sprague-Dawley rats underwent complete spinal cord transection, or cord compression by application of an aneurysm clip at T8 for 30 sec. Inosine (225 mg/kg) or vehicle was administered daily via intraperitoneal injection either immediately after injury or after a delay of 8 wk. At the end of treatment, voiding behavior was assessed by cystometry. Levels of synaptophysin (SYP), neurofilament 200 (NF200) and TRPV1 in bladder tissues were measured by immunofluorescence imaging. Inosine administration decreased overactivity in both SCI models, with a significant decrease in the frequency of spontaneous non-voiding contractions during filling, compared to vehicle-treated SCI rats (p<0.05), including under conditions of delayed treatment. Immunofluorescence staining demonstrated increased levels of the pan-neuronal marker SYP and the Adelta fiber marker NF200, but decreased staining for the C-fiber marker, TRPV1 in bladder tissues from inosine-treated rats compared to those from vehicle-treated animals, including after delayed treatment. These findings demonstrate that inosine prevents the development of detrusor overactivity and attenuates existing overactivity following SCI, and may achieve its effects through modulation of sensory neurotransmission. C1 [Chung, Yeun Goo; Seth, Abhishek; Doyle, Claire; Franck, Debra; Tu, Duong D.; Estrada, Carlos R.; Mauney, Joshua R.; Adam, Rosalyn M.] Boston Childrens Hosp, Urol Dis Res Ctr, Boston, MA USA. [Chung, Yeun Goo; Seth, Abhishek; Doyle, Claire; Kim, Daniel; Cristofaro, Vivian; Benowitz, Larry I.; Tu, Duong D.; Estrada, Carlos R.; Mauney, Joshua R.; Sullivan, Maryrose P.; Adam, Rosalyn M.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Kim, Daniel; Benowitz, Larry I.] Boston Childrens Hosp, Dept Neurosurg, Boston, MA USA. [Cristofaro, Vivian; Sullivan, Maryrose P.] VA Boston Healthcare Syst, Div Urol, West Roxbury, MA USA. [Cristofaro, Vivian; Sullivan, Maryrose P.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Sullivan, MP (reprint author), Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. EM msullivan@rics.bwh.harvard.edu; rosalyn.adam@childrens.harvard.edu FU Children's Urological Foundation; National Institutes of Health [R01 DK077195, P50 DK65298]; PVA Research Foundation [2909]; Department of Veterans Affairs Medical Research Service [BX001790] FX The authors acknowledge financial support from the Children's Urological Foundation, the National Institutes of Health (R01 DK077195, P50 DK65298, to R.M.A), the PVA Research Foundation (Grant 2909 to R.M.A) and Department of Veterans Affairs Medical Research Service, (BX001790 to M.P.S). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 28 TC 1 Z9 2 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 3 PY 2015 VL 10 IS 11 AR e0141492 DI 10.1371/journal.pone.0141492 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CV1QH UT WOS:000364032600033 PM 26529505 ER PT J AU Kantor, ED Rehm, CD Haas, JS Chan, AT Giovannucci, EL AF Kantor, Elizabeth D. Rehm, Colin D. Haas, Jennifer S. Chan, Andrew T. Giovannucci, Edward L. TI Trends in Prescription Drug Use Among Adults in the United States From 1999-2012 SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ESTROGEN PLUS PROGESTIN; MEDICATION USE; BLOOD-PRESSURE; HEALTH; POPULATION; HYPERTENSION; PREVALENCE; WOMEN; TRIAL AB IMPORTANCE It is important to document patterns of prescription drug use to inform both clinical practice and research. OBJECTIVE To evaluate trends in prescription drug use among adults living in the United States. DESIGN, SETTING, AND PARTICIPANTS Temporal trends in prescription drug use were evaluated using nationally representative data from the National Health and Nutrition Examination Survey (NHANES). Participants included 37 959 noninstitutionalized US adults, aged 20 years and older. Seven NHANES cycles were included (1999-2000 to 2011-2012), and the sample size per cycle ranged from 4861 to 6212. EXPOSURES Calendar year, as represented by continuous NHANES cycle. MAIN OUTCOMES AND MEASURES Within each NHANES cycle, use of prescription drugs in the prior 30 days was assessed overall and by drug class. Temporal trends across cycles were evaluated. Analyses were weighted to represent the US adult population. RESULTS Results indicate an increase in overall use of prescription drugs among US adults between 1999-2000 and 2011-2012 with an estimated 51% of US adults reporting use of any prescription drugs in 1999-2000 and an estimated 59% reporting use of any prescription drugs in 2011-2012 (difference, 8%[95% CI, 3.8%-12%]; P for trend <. 001). The prevalence of polypharmacy (use of >= 5 prescription drugs) increased from an estimated 8.2% in 1999-2000 to 15% in 2011-2012 (difference, 6.6%[95% CI, 4.4%-8.2%]; P for trend <. 001). These trends remained statistically significant with age adjustment. Among the 18 drug classes used by more than 2.5% of the population at any point over the study period, the prevalence of use increased in 11 drug classes including antihyperlipidemic agents, antidepressants, prescription proton-pump inhibitors, and muscle relaxants. CONCLUSIONS AND RELEVANCE In this nationally representative survey, significant increases in overall prescription drug use and polypharmacy were observed. These increases persisted after accounting for changes in the age distribution of the population. The prevalence of prescription drug use increased in the majority of, but not all, drug classes. C1 [Kantor, Elizabeth D.; Giovannucci, Edward L.] Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Kantor, Elizabeth D.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10017 USA. [Rehm, Colin D.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [Rehm, Colin D.] Montefiore Med Ctr, Off Community & Populat Hlth, Bronx, NY 10467 USA. [Haas, Jennifer S.] Brigham & Womens Hosp, Div Gen Internal Med & Primary Care, Boston, MA 02115 USA. [Haas, Jennifer S.] Harvard Univ, Dept Social & Behav Sci, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Chan, Andrew T.; Giovannucci, Edward L.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Chan, Andrew T.] Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA. [Giovannucci, Edward L.] Harvard Univ, Dept Nutr, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. RP Kantor, ED (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 485 Lexington Ave,Second Floor, New York, NY 10017 USA. EM kantore@mskcc.org OI REHM, COLIN/0000-0002-7644-0040 FU National Cancer Institute [T32 CA 009001]; National Institute of Diabetes and Digestive and Kidney Diseases [K24 DK098311]; Harvard Catalyst-The Harvard Clinical and Translational Science Center (National Center for Research Resources); Harvard Catalyst-The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) [UL1 TR001102]; Harvard University FX This work was conducted with support from the National Cancer Institute (support for Kantor, T32 CA 009001) and the National Institute of Diabetes and Digestive and Kidney Diseases (support for Chan, K24 DK098311). Support for Haas: Harvard Catalyst-The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award UL1 TR001102) and financial contributions from Harvard University and its affiliated academic health care centers. NR 40 TC 53 Z9 55 U1 9 U2 19 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 3 PY 2015 VL 314 IS 17 BP 1818 EP 1831 DI 10.1001/jama.2015.13766 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA CV0RO UT WOS:000363960200014 PM 26529160 ER PT J AU Natarajan, P Kohli, P Baber, U Nguyen, KDH Sartori, S Reilly, DF Mehran, R Muntendam, P Fuster, V Rader, DJ Kathiresan, S AF Natarajan, Pradeep Kohli, Puja Baber, Usman Nguyen, Khanh-Dung H. Sartori, Samantha Reilly, Dermot F. Mehran, Roxana Muntendam, Pieter Fuster, Valentin Rader, Daniel J. Kathiresan, Sekar TI Association of APOC3 Loss-of-Function Mutations With Plasma Lipids and Subclinical Atherosclerosis The Multi-Ethnic BioImage Study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Letter ID CORONARY; DISEASE C1 [Kathiresan, Sekar] Massachusetts Gen Hosp, Human Genet Res & Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Natarajan, P (reprint author), Massachusetts Gen Hosp, Human Genet Res & Cardiovasc Res Ctr, 185 Cambridge St,CPZN 5-252, Boston, MA 02114 USA. EM skathiresan1@mgh.harvard.edu RI Fuster, Valentin/H-4319-2015; OI Fuster, Valentin/0000-0002-9043-9986; Natarajan, Pradeep/0000-0001-8402-7435 FU NHLBI NIH HHS [R01HL107816, F32 HL128026, R01 HL107816, R01 HL127564, T32 HL007208, T32 HL116275, T32HL116275] NR 5 TC 9 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 3 PY 2015 VL 66 IS 18 BP 2053 EP 2055 DI 10.1016/j.jacc.2015.08.866 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CU9MM UT WOS:000363868600016 PM 26516010 ER PT J AU Gaspard, N Foreman, BP Alvarez, V Kang, CC Probasco, JC Jongeling, AC Meyers, E Espinera, A Haas, KF Schmitt, SE Gerard, EE Gofton, T Kaplan, PW Lee, JW Legros, B Szaflarski, JP Westover, BM LaRoche, SM Hirsch, LJ AF Gaspard, Nicolas Foreman, Brandon P. Alvarez, Vincent Kang, Christian Cabrera Probasco, John C. Jongeling, Amy C. Meyers, Emma Espinera, Alyssa Haas, Kevin F. Schmitt, Sarah E. Gerard, Elizabeth E. Gofton, Teneille Kaplan, Peter W. Lee, Jong W. Legros, Benjamin Szaflarski, Jerzy P. Westover, Brandon M. LaRoche, Suzette M. Hirsch, Lawrence J. CA Critical Care EEG Monitoring Res C TI New-onset refractory status epilepticus SO NEUROLOGY LA English DT Article ID INTENSIVE-CARE-UNIT; RECEPTOR ENCEPHALITIS; NORSE; PREDICTORS; MANAGEMENT; IMMUNOTHERAPY; ETIOLOGIES; MORTALITY; OUTCOMES; IMPACT AB Objectives: The aims of this study were to determine the etiology, clinical features, and predictors of outcome of new-onset refractory status epilepticus. Methods: Retrospective review of patients with refractory status epilepticus without etiology identified within 48 hours of admission between January 1, 2008, and December 31, 2013, in 13 academic medical centers. The primary outcome measure was poor functional outcome at discharge (defined as a score >3 on the modified Rankin Scale). Results: Of 130 cases, 67 (52%) remained cryptogenic. The most common identified etiologies were autoimmune (19%) and paraneoplastic (18%) encephalitis. Full data were available in 125 cases (62 cryptogenic). Poor outcome occurred in 77 of 125 cases (62%), and 28 (22%) died. Predictors of poor outcome included duration of status epilepticus, use of anesthetics, and medical complications. Among the 63 patients with available follow-up data (median 9 months), functional status improved in 36 (57%); 79% had good or fair outcome at last follow-up, but epilepsy developed in 37% with most survivors (92%) remaining on antiseizure medications. Immune therapies were used less frequently in cryptogenic cases, despite a comparable prevalence of inflammatory CSF changes. Conclusions: Autoimmune encephalitis is the most commonly identified cause of new-onset refractory status epilepticus, but half remain cryptogenic. Outcome at discharge is poor but improves during follow-up. Epilepsy develops in most cases. The role of anesthetics and immune therapies warrants further investigation. C1 [Gaspard, Nicolas; Hirsch, Lawrence J.] Yale Univ, Sch Med, Dept Neurol, Div Epilepsy & Clin Neurophysiol, New Haven, CT 06510 USA. [Gaspard, Nicolas; Hirsch, Lawrence J.] Yale Univ, Sch Med, Comprehens Epilepsy Ctr, New Haven, CT USA. [Gaspard, Nicolas; Legros, Benjamin] Univ Libre Bruxelles, Hop Erasme, Brussels, Belgium. [Foreman, Brandon P.] Univ Cincinnati, Dept Neurol & Rehabil Med, Cincinnati, OH 45221 USA. [Alvarez, Vincent] Hop Sion, Dept Neurol, Sion, Switzerland. [Alvarez, Vincent] CHU Vaudois, Dept Clin Neurosci, CH-1011 Lausanne, Switzerland. [Alvarez, Vincent; Lee, Jong W.] Harvard Univ, Sch Med, Dept Neurol, Brigham & Womens Hosp, Boston, MA 02115 USA. [Kang, Christian Cabrera; LaRoche, Suzette M.] Emory Univ, Sch Med, Atlanta, GA USA. [Probasco, John C.; Kaplan, Peter W.] Johns Hopkins Bayview Med Ctr, Dept Neurol, Baltimore, MD USA. [Probasco, John C.; Kaplan, Peter W.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Jongeling, Amy C.; Meyers, Emma] Columbia Univ, Dept Neurol, New York, NY USA. [Haas, Kevin F.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Schmitt, Sarah E.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Espinera, Alyssa; Gerard, Elizabeth E.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Gofton, Teneille] Univ Western Ontario, London, ON N6A 3K7, Canada. [Szaflarski, Jerzy P.] Univ Alabama Birmingham, Birmingham, AL USA. [Westover, Brandon M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Gaspard, N (reprint author), Yale Univ, Sch Med, Dept Neurol, Div Epilepsy & Clin Neurophysiol, New Haven, CT 06510 USA. EM ngaspard@ulb.ac.be FU American Epilepsy Society's Research Infrastructure Award FX The CCEMRC received funding from the American Epilepsy Society's Research Infrastructure Award. NR 32 TC 19 Z9 19 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD NOV 3 PY 2015 VL 85 IS 18 BP 1604 EP 1613 DI 10.1212/WNL.0000000000001940 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA CV3VP UT WOS:000364194800013 PM 26296517 ER PT J AU McLane, HC Berkowitz, AL Patenaude, BN McKenzie, ED Wolper, E Wahlster, S Fink, G Mateen, FJ AF McLane, Hannah C. Berkowitz, Aaron L. Patenaude, Bryan N. McKenzie, Erica D. Wolper, Emma Wahlster, Sarah Fink, Guenther Mateen, Farrah J. TI Availability, accessibility, and affordability of neurodiagnostic tests in 37 countries SO NEUROLOGY LA English DT Article ID AFRICA AB Objective: To determine the availability, accessibility, and affordability of EEG, EMG, CSF analysis, head CT, and brain MRI for neurologic disorders across countries. Methods: An online, 60-question survey was distributed to neurology practitioners in 2014 to assess the presence, wait time, and cost of each test in private and public health sectors. Data were stratified by World Bank country income group. Affordability was calculated with reference to the World Health Organization's definition of catastrophic health expenditure as health-related out-of-pocket expenditure of >40% of disposable household income, and assessment of providers' perceptions of affordability to the patient. Results: Availability of EEG and EMG is correlated with higher World Bank income group (correlation coefficient 0.38, test for trend p = 0.046; 0.376, p = 0.043); CSF, CT, and MRI did not show statistically significant associations with income groups. Patients in public systems wait longer for neurodiagnostic tests, especially MRI, EEG, and urgent CT (p < 0.0001). The mean cost per test, across all tests, was lower in the public vs private sector (US $55.25 vs $214.62, p < 0.001). Each drop in World Bank income group is associated with a 29% decrease in the estimated share of the population who can afford a given test (95% confidence interval -33.4, 25.2; p < 0.001). In most low-income countries surveyed, only the top 10% or 20% of the population was able to afford tests below catastrophic levels. In surveyed lower-middle-income countries, >40% of the population, on average, could not afford neurodiagnostic tests. Conclusions: Neurodiagnostic tests are least affordable in the lowest income settings. Closing this "diagnostic gap" for countries with the lowest incomes is essential. C1 [McLane, Hannah C.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Berkowitz, Aaron L.; Wahlster, Sarah; Mateen, Farrah J.] Harvard Univ, Sch Med, Boston, MA 02163 USA. [Berkowitz, Aaron L.; Wahlster, Sarah] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Patenaude, Bryan N.; Fink, Guenther] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [McKenzie, Erica D.; Wolper, Emma; Wahlster, Sarah; Mateen, Farrah J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [McKenzie, Erica D.] Queens Univ, Sch Med, Kingston, ON, Canada. [Wolper, Emma] Lesley Univ, Cambridge, MA USA. RP Mateen, FJ (reprint author), Harvard Univ, Sch Med, Boston, MA 02163 USA. EM fmateen@partners.org FU Grand Challenges Canada [338-04]; Government of Canada as part of Canadian Institute of Health Research; International Development Research Council FX Supported by Grand Challenges Canada (338-04). Grand Challenges Canada is funded by the Government of Canada as part of a consortium with the Canadian Institute of Health Research and the International Development Research Council. NR 14 TC 5 Z9 5 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0028-3878 EI 1526-632X J9 NEUROLOGY JI Neurology PD NOV 3 PY 2015 VL 85 IS 18 BP 1614 EP 1622 DI 10.1212/WNL.0000000000002090 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CV3VP UT WOS:000364194800014 PM 26446063 ER PT J AU Ranjbar, S Haridas, V Jasenosky, LD Falvo, JV Goldfeld, AE AF Ranjbar, Shahin Haridas, Viraga Jasenosky, Luke D. Falvo, James V. Goldfeld, Anne E. TI A Role for IFITM Proteins in Restriction of Mycobacterium tuberculosis Infection SO CELL REPORTS LA English DT Article ID INFLUENZA-A VIRUS; GAMMA-INTERFERONS; ALPHA-INTERFERONS; IMMUNE-RESPONSE; GENE-EXPRESSION; DENGUE VIRUS; MACROPHAGES; CELLS; REPLICATION; ATPASE AB The interferon (IFN)-induced transmembrane (IFITM) proteins are critical mediators of the host antiviral response. Here, we expand the role of IFITM proteins to host defense against intracellular bacterial infection by demonstrating that they restrict Mycobacterium tuberculosis (MTb) intracellular growth. Simultaneous knockdown of IFITM1, IFITM2, and IFITM3 by RNAi significantly enhances MTb growth in human monocytic and alveolar/epithelial cells, whereas individual overexpression of each IFITM impairs MTb growth in these cell types. Furthermore, MTb infection, Toll-like receptor 2 and 4 ligands, and several proinflammatory cytokines induce IFITM1-3 gene expression in human myeloid cells. We find that IFITM3 co-localizes with early and, in particular, late MTb phagosomes, and overexpression of IFITM3 enhances endosomal acidification in MTb-infected monocytic cells. These findings provide evidence that the antiviral IFITMs participate in the restriction of mycobacterial growth, and they implicate IFITM-mediated endosomal maturation in its antimycobacterial activity. C1 [Ranjbar, Shahin; Haridas, Viraga; Jasenosky, Luke D.; Falvo, James V.; Goldfeld, Anne E.] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. RP Ranjbar, S (reprint author), Childrens Hosp, Program Cellular & Mol Med, 300 Longwood Ave, Boston, MA 02115 USA. EM shahin.ranjbar@childrens.harvard.edu; anne.goldfeld@childrens.harvard.edu FU Annenberg Foundation; Ragon Institute of Harvard University; National Institute of Allergy and Infectious Diseases (NIAID) [R56128154]; Campbell Foundation FX This work was supported by grants to A.E.G. from the Annenberg Foundation, the Ragon Institute of Harvard University, the National Institute of Allergy and Infectious Diseases (NIAID, R56128154), and a gift from John Moores. S.R. was supported by a grant from the Campbell Foundation. We are grateful to Harry Leung, Michelle Ocana, Lai Ding, and Raphael Gaudin for critical assistance in performing the confocal microscopy and its analysis. We thank Sam Behar for helpful discussions and are indebted to Sabrina Hawthorne, Richard DeMarco, and Natasha Barteneva for invaluable help with IDEAS software and the Imagestream analysis. We also thank Judy Lieberman for helpful comments on the manuscript and Renate Hellmiss for the artwork. NR 58 TC 2 Z9 2 U1 4 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD NOV 3 PY 2015 VL 13 IS 5 BP 874 EP 883 DI 10.1016/j.celrep.2015.09.048 PG 10 WC Cell Biology SC Cell Biology GA CV1BM UT WOS:000363988100002 PM 26565900 ER PT J AU Belenky, P Ye, JD Porter, CBM Cohen, NR Lobritz, MA Ferrante, T Jain, S Korry, BJ Schwarz, EG Walker, GC Collins, JJ AF Belenky, Peter Ye, Jonathan D. Porter, Caroline B. M. Cohen, Nadia R. Lobritz, Michael A. Ferrante, Thomas Jain, Saloni Korry, Benjamin J. Schwarz, Eric G. Walker, Graham C. Collins, James J. TI Bactericidal Antibiotics Induce Toxic Metabolic Perturbations that Lead to Cellular Damage SO CELL REPORTS LA English DT Article ID OXIDATIVE DNA-DAMAGE; ESCHERICHIA-COLI; HYDROGEN-PEROXIDE; REACTIVE OXYGEN; LIPID-PEROXIDATION; MYCOBACTERIUM-TUBERCULOSIS; PROTEIN CARBONYLATION; MOLECULAR-MECHANISMS; INDUCED MUTAGENESIS; NUCLEOTIDE POOL AB Understanding how antibiotics impact bacterial metabolism may provide insight into their mechanisms of action and could lead to enhanced therapeutic methodologies. Here, we profiled the metabolome of Escherichia coli after treatment with three different classes of bactericidal antibiotics (beta-lactams, aminoglycosides, quinolones). These treatments induced a similar set of metabolic changes after 30 min that then diverged into more distinct profiles at later time points. The most striking changes corresponded to elevated concentrations of central carbon metabolites, active breakdown of the nucleotide pool, reduced lipid levels, and evidence of an elevated redox state. We examined potential end-target consequences of these metabolic perturbations and found that antibiotic-treated cells exhibited cytotoxic changes indicative of oxidative stress, including higher levels of protein carbonylation, malondialdehyde adducts, nucleotide oxidation, and double-strand DNA breaks. This work shows that bactericidal antibiotics induce a complex set of metabolic changes that are correlated with the buildup of toxic metabolic by-products. C1 [Belenky, Peter; Ye, Jonathan D.; Jain, Saloni; Schwarz, Eric G.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Belenky, Peter; Ye, Jonathan D.; Jain, Saloni; Schwarz, Eric G.] Boston Univ, Ctr Synthet Biol, Boston, MA 02215 USA. [Belenky, Peter; Korry, Benjamin J.] Brown Univ, Dept Mol Microbiol & Immunol, Providence, RI 02912 USA. [Porter, Caroline B. M.; Cohen, Nadia R.; Lobritz, Michael A.; Jain, Saloni; Collins, James J.] MIT, Dept Biol Engn, Inst Med Engn & Sci, Cambridge, MA 02139 USA. [Porter, Caroline B. M.; Cohen, Nadia R.; Lobritz, Michael A.; Jain, Saloni; Collins, James J.] MIT, Synthet Biol Ctr, Cambridge, MA 02139 USA. [Porter, Caroline B. M.; Lobritz, Michael A.; Collins, James J.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Porter, Caroline B. M.; Cohen, Nadia R.; Lobritz, Michael A.; Ferrante, Thomas; Collins, James J.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA. [Walker, Graham C.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Lobritz, Michael A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02115 USA. RP Belenky, P (reprint author), Boston Univ, Dept Biomed Engn, 36 Cummington Mall, Boston, MA 02215 USA. EM peter_belenky@brown.edu; jimjc@mit.edu FU NIH Director's Pioneer Award Program; Howard Hughes Medical Institute; Wyss Institute for Biologically Inspired Engineering, a Defense Threat Reduction Agency [HDTRA1-15-1-0051]; NIH [R01 CA021615] FX We thank Susan M. Rosenberg for generously providing the GamGFP strain used in this study. This work was supported by the NIH Director's Pioneer Award Program (J.J.C.), the Howard Hughes Medical Institute, the Wyss Institute for Biologically Inspired Engineering, a Defense Threat Reduction Agency grant HDTRA1-15-1-0051 (J.J.C.), and NIH grant R01 CA021615 (G.C.W.). G.C.W. is an American Cancer Society Professor. NR 94 TC 24 Z9 25 U1 9 U2 28 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD NOV 3 PY 2015 VL 13 IS 5 BP 968 EP 980 DI 10.1016/j.celrep.2015.09.059 PG 13 WC Cell Biology SC Cell Biology GA CV1BM UT WOS:000363988100012 PM 26565910 ER PT J AU Legault, JT Strittmatter, L Tardif, J Sharma, R Tremblay-Vaillancourt, V Aubut, C Boucher, G Clish, CB Cyr, D Daneault, C Waters, PJ Vachon, L Morin, C Laprise, C Rioux, JD Mootha, VK Des Rosiers, C AF Legault, Julie Thompson Strittmatter, Laura Tardif, Jessica Sharma, Rohit Tremblay-Vaillancourt, Vanessa Aubut, Chantale Boucher, Gabrielle Clish, Clary B. Cyr, Denis Daneault, Caroline Waters, Paula J. Vachon, Luc Morin, Charles Laprise, Catherine Rioux, John D. Mootha, Vamsi K. Des Rosiers, Christine CA LSFC Consortium TI A Metabolic Signature of Mitochondrial Dysfunction Revealed through a Monogenic Form of Leigh Syndrome SO CELL REPORTS LA English DT Article ID C-OXIDASE DEFICIENCY; ACID BETA-OXIDATION; MASS-SPECTROMETRY; INSULIN-RESISTANCE; 2-HYDROXYBUTYRIC ACID; ALPHA-KETOBUTYRATE; GAS-CHROMATOGRAPHY; DISORDERS; DISEASES; LRPPRC AB A decline in mitochondrial respiration represents the root cause of a large number of inborn errors of metabolism. It is also associated with common age-associated diseases and the aging process. To gain insight into the systemic, biochemical consequences of respiratory chain dysfunction, we performed a case-control, prospective metabolic profiling study in a genetically homogenous cohort of patients with Leigh syndrome French Canadian variant, a mitochondrial respiratory chain disease due to loss-of-function mutations in LRPPRC. We discovered 45 plasma and urinary analytes discriminating patients from controls, including classic markers of mitochondrial metabolic dysfunction (lactate and acylcarnitines), as well as unexpected markers of cardiometabolic risk (insulin and adiponectin), amino acid catabolism linked to NADH status (alpha-hydroxybutyrate), and NAD + biosynthesis (kynurenine and 3-hydroxyanthranilic acid). Our study identifies systemic, metabolic pathway derangements that can lie downstream of primary mitochondrial lesions, with implications for understanding how the organelle contributes to rare and common diseases. C1 [Legault, Julie Thompson; Des Rosiers, Christine] Univ Montreal, Dept Nutr, Montreal, PQ H3C 3J7, Canada. [Rioux, John D.] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. [Legault, Julie Thompson; Boucher, Gabrielle; Daneault, Caroline; Rioux, John D.; Des Rosiers, Christine] Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada. [Mootha, Vamsi K.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. [Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Strittmatter, Laura; Sharma, Rohit; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02445 USA. [Tardif, Jessica; Tremblay-Vaillancourt, Vanessa; Aubut, Chantale; Laprise, Catherine] Univ Quebec Chicoutimi, Dept Sci Fondamentales, Chicoutimi, PQ G7H 2B1, Canada. [Aubut, Chantale; Morin, Charles] Ctr Sante & Serv Sociaux Chicoutimi, Chicoutimi, PQ G7H 5H6, Canada. [Clish, Clary B.; Mootha, Vamsi K.] Broad Inst, Cambridge, MA 02142 USA. [Cyr, Denis; Waters, Paula J.] CHU Sherbrooke, Med Genet Serv, Sherbrooke, PQ J1H 5N4, Canada. [Vachon, Luc] LSFC Consortium, Montreal, PQ, Canada. RP Mootha, VK (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. EM vamsi@hms.harvard.edu; christine.des.rosiers@umontreal.ca RI Rioux, John/A-9599-2015; OI Rioux, John/0000-0001-7560-8326; Bemeur, Chantal/0000-0003-2757-5958 FU Canadian Institutes of Health Research (CIHR) [102168]; NIH [R01DK081457]; Association de l'acidose lactique (AAL); Fonds de la Recherche en Santedu Quebec; Fondation du Grand Defi Pierre Lavoie; Corporation de recherche et d'action sur les maladies hereditaires (COR-AMH) FX This work was supported by the Canadian Institutes of Health Research (CIHR) (grant no. 102168 awarded to C.D.R., C.L., J.D.R., and E.A.S.), NIH (R01DK081457 to V.K.M.), Association de l'acidose lactique (AAL), Fonds de la Recherche en Santedu Quebec, Fondation du Grand Defi Pierre Lavoie, and Corporation de recherche et d'action sur les maladies hereditaires (COR-AMH). V.K.M. is an Investigator of the Howard Hughes Medical Institute. J.D.R. holds the Canada Research Chair in Genetics and Genomic Medicine. R.S. is supported by an NIH T32 grant through the Harvard Medical School Genetics Training Program. We thank B. Maranda for helpful discussions, J. Landry for subject recruitment and sample collection, I. Robillard Frayne for GC-MS expertise, C. Beauchamp for genotyping, S. Cherkaoui for bioinformatics, K.A. Pierce and K. Bullock for metabolic profiling at the Broad Institute, and T. Gagnon at Centre hospitalier universitaire de Sherbrooke. We gratefully acknowledge LSFC patients, their families, and the AAL (http://www.aal.qc.ca). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 72 TC 5 Z9 6 U1 2 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 2211-1247 J9 CELL REP JI Cell Reports PD NOV 3 PY 2015 VL 13 IS 5 BP 981 EP 989 DI 10.1016/j.celrep.2015.09.054 PG 9 WC Cell Biology SC Cell Biology GA CV1BM UT WOS:000363988100013 ER PT J AU Golovko, D Kedrin, D Yilmaz, OH Roper, J AF Golovko, Daniel Kedrin, Dmitriy Yilmaz, Oemer H. Roper, Jatin TI Colorectal cancer models for novel drug discovery SO EXPERT OPINION ON DRUG DISCOVERY LA English DT Review DE colorectal cancer mouse models; intestinal organoid; patient-derived xenograft; transgenic colorectal cancer mouse model ID FAMILIAL ADENOMATOUS POLYPOSIS; MULTIPLE INTESTINAL NEOPLASIA; PATIENT-DERIVED XENOGRAFTS; ENGINEERED MOUSE MODELS; SODIUM-INDUCED COLITIS; IN-VITRO EXPANSION; COLON-CANCER; STEM-CELLS; APC GENE; TUMOR XENOGRAFTS AB Introduction: Despite increased screening rates and advances in targeted therapy, colorectal cancer (CRC) remains the third leading cause of cancer-related mortality. CRC models that recapitulate key features of human disease are essential to the development of novel and effective therapeutics. Classic methods of modeling CRC such as human cell lines and xenograft mice, while useful for many applications, carry significant limitations. Recently developed in vitro and in vivo models overcome some of these deficiencies and thus can be utilized to better model CRC for mechanistic and translational research. Areas covered: The authors review established models of in vitro cell culture and describe advances in organoid culture for studying normal and malignant intestine. They also discuss key features of classic xenograft models and describe other approaches for in vivo CRC research, including patient-derived xenograft, carcinogen-induced, orthotopic transplantation and transgenic mouse models. We also describe mouse models of metastatic CRC. Expert opinion: No single model is optimal for drug discovery in CRC. Genetically engineered models overcome many limitations of xenograft models. Three-dimensional organoids can be efficiently derived from both normal and malignant tissue for large-scale in vitro and in vivo (transplantation) studies and are thus a significant advance in CRC drug discovery. C1 [Golovko, Daniel; Roper, Jatin] Tufts Med Ctr, Div Gastroenterol & Mol Oncol, Res Inst, Boston, MA 02111 USA. [Kedrin, Dmitriy; Yilmaz, Oemer H.; Roper, Jatin] MIT, Dept Biol, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Kedrin, Dmitriy; Yilmaz, Oemer H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kedrin, Dmitriy] Harvard Univ, Sch Med, Div Gastroenterol, Boston, MA 02114 USA. [Yilmaz, Oemer H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Roper, J (reprint author), Tufts Med Ctr, Div Gastroenterol & Mol Oncol, Res Inst, Boston, MA 02111 USA. EM jroper@tuftsmedicalcenter.org OI Roper, Jatin/0000-0002-8851-1352 FU Department of Defense through the Peer Reviewed Cancer Research Program Career Development Award [CA120198]; Tufts University School of Medicine through the Earl P. Charlton Fund Research Award; Tufts University School of Medicine through the Rozan Research Fund Pilot Award; V Scholar Award through the V Foundation for Cancer Research; National Institutes of Health (NIH) through the Center for the Study of Inflammatory Bowl Diseases from the Massachusetts General Hospital [DK043351]; National Institute of Aging [NIA R00 AG045144]; NIH Cancer Center Support (core) grant [P30-CA14051]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) T32 grant [DK007191] FX J Roper was supported by the Department of Defense through the Peer Reviewed Cancer Research Program Career Development Award CA120198 and by the Tufts University School of Medicine through the Earl P. Charlton Fund Research Award and Rozan Research Fund Pilot Award. J Roper and OH Yilmaz are supported with a V Scholar Award through the V Foundation for Cancer Research. OH Yilmaz is supported by a National Institutes of Health (NIH) grant DK043351 through the Center for the Study of Inflammatory Bowl Diseases from the Massachusetts General Hospital as well as National Institute of Aging grant NIA R00 AG045144 and NIH Cancer Center Support (core) grant P30-CA14051. D Kedrin is also supported by a National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) T32 grant DK007191. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 101 TC 1 Z9 1 U1 8 U2 16 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1746-0441 EI 1746-045X J9 EXPERT OPIN DRUG DIS JI Expert. Opin. Drug Discov. PD NOV 2 PY 2015 VL 10 IS 11 BP 1217 EP 1229 DI 10.1517/17460441.2015.1079618 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DD5LX UT WOS:000369966400003 PM 26295972 ER PT J AU de Steiger, RN Muratoglu, O Lorimer, M Cuthbert, AR Graves, SE AF de Steiger, Richard N. Muratoglu, Orhun Lorimer, Michelle Cuthbert, Alana R. Graves, Stephen E. TI Lower prosthesis-specific 10-year revision rate with cross-linked than with non-crosslinked polyethylene in primary total knee arthroplasty 386,104 procedures from the Australian Orthopaedic Association National Joint Replacement Registry SO ACTA ORTHOPAEDICA LA English DT Article ID TOTAL HIP-ARTHROPLASTY; WEAR PERFORMANCE; FOLLOW-UP; SIMULATOR AB Background and purpose - While highly crosslinked polyethylene has shown reduced in vivo wear and lower rates of revision for total hip arthroplasty, there have been few long-term studies on its use in total knee arthroplasty (TKA). We compared the rate of revision of non-crosslinked polyethylene to that of crosslinked polyethylene in patients who underwent TKA for osteoarthritis. Patients and methods - We examined data from the Australian Orthopaedic Association National Joint Replacement Registry on 302,214 primary TKA procedures with non-crosslinked polyethylene and 83,890 procedures with crosslinked polyethylene, all of which were performed for osteoarthritis. The survivorship of the different polyethylenes was estimated using the Kaplan-Meier method and was compared using proportional hazard models. Results - The 10-year cumulative revision rate for non-crosslinked polyethylene was 5.8% (95% CI: 5.7-6.0) and for crosslinked polyethylene it was 3.5% (95% CI: 3.2-3.8) (> 6.5-year HR = 2.2 (1.5-3.1); p < 0.001). There was no effect of surgical volume or method of prosthesis fixation on outcome. There were 4 different TKA designs that had a minimum of 2,500 procedures in at least 1 of the polyethylene groups and a follow-up of 5 years. 2 of these, the NexGen and the Natural Knee II, had a lower rate of revision for crosslinked polyethylene. The Scorpio NRG/Series 7000 and the Triathlon Knee did not show a lower rate of revision for crosslinked polyethylene. Interpretation - There is a lower rate of revision for crosslinked polyethylene in TKA, and this appears to be prosthesis-specific and when it occurs is most evident in patients < 65 years of age. The difference in revision rates was mainly due to revisions because of lysis and loosening. C1 [de Steiger, Richard N.; Graves, Stephen E.] Univ Adelaide, Australian Orthopaed Assoc, Natl Joint Replacement Registry, Discipline Publ Hlth, Adelaide, SA, Australia. [de Steiger, Richard N.] Univ Adelaide, Sch Populat Hlth & Clin Practice, Adelaide, SA, Australia. [Muratoglu, Orhun] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. [Lorimer, Michelle; Cuthbert, Alana R.] Univ Adelaide, Data Management & Anal Ctr, Adelaide, SA, Australia. RP de Steiger, RN (reprint author), Univ Adelaide, Australian Orthopaed Assoc, Natl Joint Replacement Registry, Discipline Publ Hlth, Adelaide, SA, Australia. EM rdesteiger@aoanjrr.org.au NR 12 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1745-3674 EI 1745-3682 J9 ACTA ORTHOP JI Acta Orthop. PD NOV 2 PY 2015 VL 86 IS 6 BP 721 EP 727 DI 10.3109/17453674.2015.1065046 PG 7 WC Orthopedics SC Orthopedics GA CX1VU UT WOS:000365484500015 PM 26119884 ER PT J AU Carpenter, JS Woods, NF Otte, JL Guthrie, KA Hohensee, C Newton, KM Joffe, H Cohen, L Sternfeld, B Lau, RJ Reed, SD LaCroix, AZ AF Carpenter, J. S. Woods, N. F. Otte, J. L. Guthrie, K. A. Hohensee, C. Newton, K. M. Joffe, H. Cohen, L. Sternfeld, B. Lau, R. J. Reed, S. D. LaCroix, A. Z. TI MsFLASH participants' priorities for alleviating menopausal symptoms SO CLIMACTERIC LA English DT Article DE MENOPAUSE; SYMPTOMS; VASOMOTOR SYMPTOMS; SLEEP DISTURBANCES; FATIGUE; COGNITIVE FUNCTIONING ID MIDLIFE WOMENS HEALTH; SLEEP QUALITY INDEX; INSOMNIA SEVERITY INDEX; HOT FLASHES; BREAST-CANCER; TRANSITION; CLUSTERS; POPULATION; EXPERIENCE; DESIGN AB Objective To describe self-reported menopausal symptom priorities and their association with demographics and other symptoms among participants in an intervention trial for vasomotor symptoms (VMS).Methods Cross-sectional study embedded in the MsFLASH 02 trial, a three-by-two factorial design of yoga vs. exercise vs. usual activity and omega-3-fatty acid vs. placebo. At baseline, women (n=354) completed hot flush diaries, a card sort task to prioritize symptoms they would most like to alleviate, and standardized questionnaires.Results The most common symptom priorities were: VMS (n=322), sleep (n=191), concentration (n=140), and fatigue (n=116). In multivariate models, women who chose VMS as their top priority symptom (n=210) reported significantly greater VMS severity (p=0.004) and never smoking (p=0.012), and women who chose sleep as their top priority symptom (n=100) were more educated (p0.001) and had worse sleep quality (p<0.001). ROC curves identified sleep scale scores that were highly predictive of ranking sleep as a top priority symptom.Conclusions Among women entering an intervention trial for VMS and with relatively low prevalence of depression and anxiety, VMS was the priority symptom for treatment. A card sort may be a valid tool for quickly assessing symptom priorities in clinical practice and research. C1 [Carpenter, J. S.; Otte, J. L.] Indiana Univ, Sch Nursing, Sci Nursing Care, Indianapolis, IN 46202 USA. [Woods, N. F.] Univ Washington, Biobehav Nursing, Seattle, WA 98195 USA. [Guthrie, K. A.; Hohensee, C.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Newton, K. M.] Grp Hlth Res Inst, Seattle, WA USA. [Joffe, H.] Harvard Univ, Brigham & Womens Hosp, Dept Psychiat, Sch Med, Boston, MA 02115 USA. [Joffe, H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cohen, L.] Massachusetts Gen Hosp, Ctr Womens Mental Hlth, Boston, MA 02114 USA. [Cohen, L.] Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA 02114 USA. [Sternfeld, B.] Kaiser Permanent Med Program Northern Calif, Div Res, Oakland, CA USA. [Lau, R. J.] Indiana Univ, Sch Med, Dept Obstet & Gynecol, Indianapolis, IN 46202 USA. [Reed, S. D.] Univ Washington, Sch Med, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Reed, S. D.] Univ Washington, Sch Med, Dept Epidemiol, Seattle, WA 98195 USA. [LaCroix, A. Z.] Univ Calif San Diego, Dept Prevent Med, San Diego, CA 92103 USA. RP Carpenter, JS (reprint author), Indiana Univ, Sch Nursing, 1111 Middle Dr NU 340G, Indianapolis, IN 46202 USA. EM carpentj@iu.edu FU National Institutes of Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Center for Complementary and Alternative Medicine (NCCAM); Office of Research on Women's Health (ORWH); NIA [U01 AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, U01AG032700]; Indiana Clinical and Translational Sciences Institute from the NIH, National Center for Research Resources, Clinical and Translational Sciences Award [UL1RR02571] FX This study was funded by the National Institutes of Health as a cooperative agreement issued by the National Institute on Aging (NIA), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Center for Complementary and Alternative Medicine (NCCAM), the Office of Research on Women's Health (ORWH), and grants U01 AG032656, U01AG032659, U01AG032669, U01AG032682, U01AG032699, U01AG032700 from the NIA. At Indiana University, the project was funded in part with support from the Indiana Clinical and Translational Sciences Institute, grant UL1RR02571 from the NIH, National Center for Research Resources, Clinical and Translational Sciences Award. NR 30 TC 2 Z9 2 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1369-7137 EI 1473-0804 J9 CLIMACTERIC JI Climacteric PD NOV 2 PY 2015 VL 18 IS 6 BP 859 EP 866 DI 10.3109/13697137.2015.1083003 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CX3QK UT WOS:000365614000018 PM 26517583 ER PT J AU Goldstein, DP Berkowitz, RS Horowitz, NS AF Goldstein, Donald P. Berkowitz, Ross S. Horowitz, Neil S. TI Optimal management of low-risk gestational trophoblastic neoplasia SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE actinomycin D; EMACO; gestational trophoblastic disease; gestational trophoblastic neoplasia; methotrexate; molar pregnancy; non-metastatic disease; sequential chemotherapy; subsequent pregnancy ID SINGLE-AGENT METHOTREXATE; PREGNANCY FOLLOWING CHEMOTHERAPY; RETROSPECTIVE COHORT SURVEY; LOW-DOSE METHOTREXATE; GERM-CELL TUMORS; ACTINOMYCIN-D; MOLAR PREGNANCY; FOLINIC ACID; DISEASE-CENTER; PULSE METHOTREXATE AB Low-risk gestational trophoblastic neoplasia is a highly curable form of gestational trophoblastic neoplasia that arises largely from molar pregnancy and, on rare occasions, from other types of gestations. Risk is defined as the risk of developing drug resistance as determined by the WHO Prognostic Scoring System. All patients with non-metastatic disease and patients with risk scores <7 are considered to have low-risk disease. The sequential use of methotrexate and actinomycin D is associated with a complete remission rate of 80%. The most commonly utilized regimen for the treatment of patients resistant to single-agent chemotherapy is a multiagent regimen consisting of etoposide, methotrexate, actinomycin D, vincristine and cyclophosphamide. The measurement of human chorionic gonadotropin provides an accurate and reliable tumor marker for diagnosis, monitoring the effects of chemotherapy and follow-up to determine recurrence. Pregnancy is allowed after 12 months of normal serum tumor marker. Pregnancy outcomes are similar to those of normal population. C1 [Goldstein, Donald P.] Dana Farber Canc Inst, Div Gynecol Oncol, New England Trophoblast Dis Ctr, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Goldstein, DP (reprint author), Dana Farber Canc Inst, Div Gynecol Oncol, New England Trophoblast Dis Ctr, Boston, MA 02115 USA. EM dgoldstein@partners.org NR 87 TC 0 Z9 0 U1 2 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1473-7140 EI 1744-8328 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD NOV 2 PY 2015 VL 15 IS 11 BP 1293 EP 1304 DI 10.1586/14737140.2015.1088786 PG 12 WC Oncology SC Oncology GA CW9GB UT WOS:000365305700002 PM 26517533 ER PT J AU Varraso, R Camargo, CA AF Varraso, Raphaelle Camargo, Carlos A., Jr. TI The influence of processed meat consumption on chronic obstructive pulmonary disease SO EXPERT REVIEW OF RESPIRATORY MEDICINE LA English DT Article DE Chronic obstructive pulmonary disease; cured meat; diet; healthy diet; lung function; nutritional factors; processed meat; smoking ID GLYCATION END-PRODUCTS; LUNG-FUNCTION; DIETARY PATTERNS; UNITED-STATES; RISK-FACTORS; US WOMEN; GLOBAL BURDEN; CURED MEATS; VITAMIN-D; COPD AB Although cigarette smoking is the predominant risk factor for chronic obstructive pulmonary disease (COPD), many smokers do not develop COPD. Relatively little attention has been paid to other modifiable factors, such as diet, and how they might affect COPD risk. Recent studies have suggested that processed meat intake may adversely affect lung function and increase risk of developing COPD. However, the role of processed meat in the pathogenesis of COPD is largely unknown and mechanistic studies are lacking. We discuss several areas of future research that would advance our understanding regarding the role of processed meat and, more generally of diet, in the onset and in the clinical evolution of COPD. C1 [Varraso, Raphaelle] INSERM, VIMA Aging & Chron Dis Epidemiol & Publ Hlth Appr, U1168, Villejuif, France. [Varraso, Raphaelle] Univ Versailles St Quentin En Yvelines, UVSQ, UMR S 1168, St Quentin En Yvelines, France. [Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Varraso, R (reprint author), INSERM, VIMA Aging & Chron Dis Epidemiol & Publ Hlth Appr, U1168, Villejuif, France. EM raphaelle.varraso@inserm.fr RI Varraso, Raphaelle/R-8740-2016 OI Varraso, Raphaelle/0000-0002-3338-7825 NR 63 TC 0 Z9 0 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1747-6348 EI 1747-6356 J9 EXPERT REV RESP MED JI Expert Rev. Respir. Med. PD NOV 2 PY 2015 VL 9 IS 6 BP 703 EP 710 DI 10.1586/17476348.2015.1105743 PG 8 WC Respiratory System SC Respiratory System GA CX4RX UT WOS:000365689100001 PM 26503123 ER PT J AU Lucas, DM Ruppert, AS Lozanski, G Dewald, GW Lozanski, A Claus, R Plass, C Flinn, IW Neuberg, DS Paietta, EM Bennett, JM Jelinek, DF Gribben, JG Hussein, MA Appelbaum, FR Larson, RA Moore, DF Tallman, MS Byrd, JC Grever, MR AF Lucas, David M. Ruppert, Amy S. Lozanski, Gerard Dewald, Gordon W. Lozanski, Arletta Claus, Rainer Plass, Christoph Flinn, Ian W. Neuberg, Donna S. Paietta, Elisabeth M. Bennett, John M. Jelinek, Diane F. Gribben, John G. Hussein, Mohamad A. Appelbaum, Frederick R. Larson, Richard A. Moore, Dennis F., Jr. Tallman, Martin S. Byrd, John C. Grever, Michael R. TI Cytogenetic prioritization with inclusion of molecular markers predicts outcome in previously untreated patients with chronic lymphocytic leukemia treated with fludarabine or fludarabine plus cyclophosphamide: a long-term follow-up study of the US intergroup phase III trial E2997 SO LEUKEMIA & LYMPHOMA LA English DT Article DE Fludarabine; cyclophosphamide; chemotherapy; chronic lymphocytic leukemia ID GENE MUTATION STATUS; ZAP-70 EXPRESSION; NOTCH1 MUTATIONS; DISEASE PROGRESSION; INITIAL THERAPY; OPEN-LABEL; METHYLATION; PROGNOSIS; IBRUTINIB; CHLORAMBUCIL AB Fludarabine (F) and cyclophosphamide (C) remain backbones of up-front chemotherapy regimens for chronic lymphocytic leukemia (CLL). We report long-term follow-up of a randomized F vs. FC trial in untreated CLL#. With median follow-up of 88 months, estimated median progression-free survival (PFS) was 19.3 vs. 48.1 months for F (n = 109) and FC (n = 118), respectively (p < 0.0001), and median overall survival (OS) was 88.0 vs. 79.1 months (p = 0.96). In multivariable analyses, variables associated with inferior PFS and OS respectively were age (p = 0.002, p < 0.001), Rai stage (p = 0.006, p = 0.02) and sex (p = 0.03, PFS only). Del(17)(p13.1) predicted shorter PFS and OS (p < 0.0001 for each), as did del(11q)(22.3) (p < 0.0001, p = 0.005, respectively), trisomy 12 with mutated Notch1 (p = 0.003, p = 0.03, respectively) and unmutated IGHV (p = 0.009, p = 0.002, respectively), all relative to patients without these features. These data confirm results from shorter follow-up and further justify targeted therapies for CLL. C1 [Lucas, David M.; Ruppert, Amy S.; Lozanski, Gerard; Lozanski, Arletta; Byrd, John C.; Grever, Michael R.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Dewald, Gordon W.; Jelinek, Diane F.] Mayo Clin, Rochester, MN USA. [Claus, Rainer] Univ Freiburg, Med Ctr, Freiburg, Germany. [Claus, Rainer; Plass, Christoph] German Canc Res Ctr, Heidelberg, Germany. [Flinn, Ian W.] Sarah Cannon Res Inst & Tennessee Oncol, Nashville, TN USA. [Neuberg, Donna S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Paietta, Elisabeth M.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Bennett, John M.] Univ Rochester, Rochester, NY USA. [Gribben, John G.] Queen Mary Univ London, Barts Canc Inst, London, England. [Hussein, Mohamad A.] Celgene Corp, Summit, NJ USA. [Appelbaum, Frederick R.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Larson, Richard A.] Univ Chicago, Chicago, IL 60637 USA. [Moore, Dennis F., Jr.] Canc Ctr Kansas, Wichita, KS USA. [Tallman, Martin S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Lucas, DM (reprint author), Ohio State Univ, Ctr Comprehens Canc, 410 West 12th Ave,Room 455, Columbus, OH 43210 USA. EM david.lucas@osumc.edu RI Lucas, David/E-3555-2011 FU US National Institutes of Health (NIH) [R01 CA88647, P50 CA140158]; NIH [CA23318, CA66636, CA21115, CA180820, CA180794, CA16116, CA180802, CA180791, CA14958, CA11083, CA13650, CA180790, CA35431, CA31946, CA32102, CA20319, CA17145, P01 CA101956]; German Research Society (DFG); German Cancer Aid (Max Eder stipend) [DKH 110461]; German Cancer Research Center; German Cancer Consortium FX The authors would like to thank the patients and physicians who participated in E2997 and contributed samples, and the cooperative groups (ECOG, SWOG and CALGB, now Alliance) that joined in this effort. The correlative studies described here were supported by the US National Institutes of Health (NIH) (R01 CA88647 and P50 CA140158). The E2997 clinical study was coordinated by the ECOG-ACRIN Cancer Research Group (Robert L. Comis and Mitchell D. Schnall, Co-Chairs) and supported in part by NIH grants CA23318, CA66636, CA21115, CA180820, CA180794, CA16116, CA180802, CA180791, CA14958, CA11083, CA13650, CA180790, CA35431, CA31946, CA32102, CA20319 and CA17145. R.C. receives a fellowship from the German Research Society (DFG) and is supported by the German Cancer Aid (Max Eder stipend, DKH 110461). C.P. is supported by the NIH (P01 CA101956), the German Cancer Research Center and the German Cancer Consortium. The content of this paper is solely the responsibility of the authors, and does not necessarily represent the official views of the NIH. NR 43 TC 2 Z9 2 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD NOV 2 PY 2015 VL 56 IS 11 BP 3031 EP 3037 DI 10.3109/10428194.2015.1023800 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA CX2IK UT WOS:000365520200007 PM 25721902 ER PT J AU Zheng, J Wang, L Lin, JH Xiao, JC Liang, SH AF Zheng, Jian Wang, Lu Lin, Jin-Hong Xiao, Ji-Chang Liang, Steven H. TI Difluorocarbene-Derived Trifluoromethylthiolation and [F-18]Trifluoromethylthiolation of Aliphatic Electrophiles SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE carbenes; fluorine; isotopic labeling; positron emission tomography; sulfur ID POSITRON-EMISSION-TOMOGRAPHY; COPPER-CATALYZED TRIFLUOROMETHYLTHIOLATION; ARYL BORONIC ACIDS; ELEMENTAL SULFUR; OXIDATIVE TRIFLUOROMETHYLTHIOLATION; SILVER(I) TRIFLUOROMETHANETHIOLATE; DIFLUOROMETHYLENE PHOSPHOBETAINE; TERMINAL ALKYNES; ARENES; IODIDES AB The first trifluoromethylthiolation and [F-18]trifluoromethylthiolation of alkyl electrophiles with insitu generated difluorocarbene in the presence of elemental sulfur and external (radioactive) fluoride ion is described. This transition-metal-free approach is high yielding, compatible with a variety of functional groups, and operated under mild reaction conditions. The conceptual advantage of this exogenous-fluoride-mediated transformation enables unprecedented syntheses of [F-18]CF3S-labeled molecules from most commonly used [F-18]fluoride ions. The rapid radiochemical reaction time (1min) and high functional-group tolerance allow access to a variety of aliphatic [F-18]CF3S compounds in high yields. C1 [Zheng, Jian; Lin, Jin-Hong; Xiao, Ji-Chang] Chinese Acad Sci, Shanghai Inst Organ Chem, Key Lab Organofluorine Chem, Shanghai 200032, Peoples R China. [Wang, Lu; Liang, Steven H.] Harvard Univ, Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Sch Med, Boston, MA USA. [Wang, Lu; Liang, Steven H.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Xiao, JC (reprint author), Chinese Acad Sci, Shanghai Inst Organ Chem, Key Lab Organofluorine Chem, 345 Lingling Rd, Shanghai 200032, Peoples R China. EM jchxiao@sioc.ac.cn; liang.steven@mgh.harvard.edu FU National Natural Science Foundation [21032006, 21172240, 21421002, 21472222, 21502214]; National Basic Research Program of China [2015CB931900, 2012CBA01200]; Chinese Academy of Sciences [XDA02020105, XDA02020106]; NIH FX This work was financially supported by the National Natural Science Foundation (21032006, 21172240, 21421002, 21472222, 21502214), National Basic Research Program of China (2015CB931900, 2012CBA01200), and the Chinese Academy of Sciences (XDA02020105, XDA02020106). We thank Professor Jinbo Hu for helpful discussion. S.H.L is a recipient of an NIH career development award. NR 100 TC 16 Z9 16 U1 14 U2 46 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 1433-7851 EI 1521-3773 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PD NOV 2 PY 2015 VL 54 IS 45 BP 13236 EP 13240 DI 10.1002/anie.201505446 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA CU7BY UT WOS:000363691500011 PM 26387796 ER PT J AU Yetish, G Kaplan, H Gurven, M Wood, B Pontzer, H Manger, PR Wilson, C McGregor, R Siegel, JM AF Yetish, Gandhi Kaplan, Hillard Gurven, Michael Wood, Brian Pontzer, Herman Manger, Paul R. Wilson, Charles McGregor, Ronald Siegel, Jerome M. TI Natural Sleep and Its Seasonal Variations in Three Pre-industrial Societies SO CURRENT BIOLOGY LA English DT Article ID SKIN-TEMPERATURE; HUNTER-GATHERER; KUNG-SAN; INFECTION; ENTRAINMENT; DURATION; LIGHT; DAWN AB How did humans sleep before the modern era? Because the tools to measure sleep under natural conditions were developed long after the invention of the electric devices suspected of delaying and reducing sleep, we investigated sleep in three preindustrial societies [1-3]. We find that all three show similar sleep organization, suggesting that they express core human sleep patterns, most likely characteristic of pre-modern era Homo sapiens. Sleep periods, the times from onset to offset, averaged 6.9-8.5 hr, with sleep durations of 5.7-7.1 hr, amounts near the low end of those industrial societies [4-7]. There was a difference of nearly 1 hr between summer and winter sleep. Daily variation in sleep duration was strongly linked to time of onset, rather than offset. None of these groups began sleep near sunset, onset occurring, on average, 3.3 hr after sunset. Awakening was usually before sunrise. The sleep period consistently occurred during the night-time period of falling environmental temperature, was not interrupted by extended periods of waking, and terminated, with vasoconstriction, near the nadir of daily ambient temperature. The daily cycle of temperature change, largely eliminated from modern sleep environments, may be a potent natural regulator of sleep. Light exposure was maximal in the morning and greatly decreased at noon, indicating that all three groups seek shade at midday and that light activation of the suprachiasmatic nucleus is maximal in the morning. Napping occurred on <7% of days in winter and <22% of days in summer. Mimicking aspects of the natural environment might be effective in treating certain modern sleep disorders. C1 [Yetish, Gandhi; Kaplan, Hillard] Univ New Mexico, Dept Anthropol, Albuquerque, NM 87131 USA. [Gurven, Michael] Univ Calif Santa Barbara, Dept Anthropol, Santa Barbara, CA 93106 USA. [Wood, Brian] Yale Univ, Dept Anthropol, New Haven, CT 06511 USA. [Pontzer, Herman] CUNY Hunter Coll, Dept Anthropol, New York, NY 10065 USA. [Manger, Paul R.] Univ Witwatersrand, Sch Anat Sci, ZA-2193 Johannesburg, South Africa. [Wilson, Charles] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. [Wilson, Charles] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA. [McGregor, Ronald; Siegel, Jerome M.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Siegel, Jerome M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 91343 USA. [Siegel, Jerome M.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA. RP Siegel, JM (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. EM jsiegel@ucla.edu FU National Research Foundation of South Africa; National Science Foundation [1062879]; NIH/NIA [R01AG024119]; [MH064109]; [DA034748] FX We thank Oma Tsamkgao for translation, assistance with the Actiwatch, and iButton application, and various associated tasks; Adhil Bhagwandin, Leigh-Anne Dell, and Josh Davimes for assistance with setup of studies in Namibia; Alfredo Maito Nose and Basilio Vie Tayo for translation, long hours of hard work, and comprehensive field guidance in Bolivia; Keng-Tee Chew and Ming-Fung Wu for help with data analysis; Eus Van Someren for advice on the use of iButtons; and Craig Heller for advice on ambient temperature recording. J.M.S. was supported by MH064109 and DA034748. M.G., H.K., and G.Y. were supported by NIH/NIA grant no. R01AG024119. P.R.M. was supported by funding from the National Research Foundation of South Africa. B.W. received support from the National Science Foundation grant no. 1062879. An abstract of this work was submitted to the World Federation of Sleep Research Societies meeting on April 6, 2015. NR 37 TC 21 Z9 22 U1 7 U2 32 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0960-9822 EI 1879-0445 J9 CURR BIOL JI Curr. Biol. PD NOV 2 PY 2015 VL 25 IS 21 BP 2862 EP 2868 DI 10.1016/j.cub.2015.09.046 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA CV4UR UT WOS:000364262500031 PM 26480842 ER PT J AU Gradus, JL Smith, BN Vogt, D AF Gradus, Jaimie L. Smith, Brian N. Vogt, Dawne TI Family support, family stress, and suicidal ideation in a combat-exposed sample of Operation Enduring Freedom/Operation Iraqi Freedom veterans SO ANXIETY STRESS AND COPING LA English DT Article DE stress disorders; traumatic; stress; psychological; social support; veterans; suicidal ideation ID SOCIAL SUPPORT; DISORDERS; SYMPTOMS; RISK; HEALTH; PTSD AB Background and Objectives: Deployment-related risk factors for suicidal ideation among Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) veterans have received a great deal of attention. Studies show that mental health symptoms mediate the association between most deployment stressors and suicidal ideation; however, family-related factors during deployment are largely unexplored. We examined posttraumatic stress disorder (PTSD) and depression symptoms as mediators of the associations between deployment family support and stress and post-deployment suicidal ideation in combat-exposed OEF/OIF veterans. Design: National cross-sectional mail survey. Methods: 1046 veterans responded to the survey. The sample for this study was 978 veterans who experienced combat. Regression-based path analyses were conducted. Results: Family support and stress had direct associations with suicidal ideation. When PTSD and depression symptoms were examined as mediators of these associations, results revealed significant indirect paths through these symptoms. Conclusions: This study contributes to the literature on suicidal ideation risk factors among OEF/OIF veterans. Deployment family support and family stress are associated with suicidal ideation; however these associations occur primarily through mental health symptomatology, consistent with findings observed for other deployment factors. This research supports ongoing efforts to treat mental health symptomatology as a means of suicide prevention. C1 [Gradus, Jaimie L.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. Boston Univ, Boston, MA 02130 USA. RP Gradus, JL (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave 116B-3, Boston, MA 02130 USA. EM Jaimie.gradus@va.gov OI Gradus, Jaimie/0000-0003-1459-5327 FU Department of Veterans Affairs, Health Services Research and Development Service "Validation of Modified DRRI Scales in a National Sample of OEF/OIF Veterans" [DHI 09-086] FX This work was supported by the Department of Veterans Affairs, Health Services Research and Development Service "Validation of Modified DRRI Scales in a National Sample of OEF/OIF Veterans" [grant number DHI 09-086], Dawne Vogt, Principal Investigator. NR 29 TC 0 Z9 0 U1 5 U2 25 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1061-5806 EI 1477-2205 J9 ANXIETY STRESS COPIN JI Anxiety Stress Coping PD NOV 2 PY 2015 VL 28 IS 6 BP 706 EP 715 DI 10.1080/10615806.2015.1006205 PG 10 WC Neurosciences; Psychiatry; Psychology, Multidisciplinary SC Neurosciences & Neurology; Psychiatry; Psychology GA CQ4AW UT WOS:000360547400007 PM 25616497 ER PT J AU Mavandadi, S Jacques, N Sayers, SL Oslin, DW AF Mavandadi, Shahrzad Jacques, Natacha Sayers, Steven L. Oslin, David W. TI Health-related social control among older men with depressive symptomatology SO AGING & MENTAL HEALTH LA English DT Article DE social support; depression; age; health behavior ID PSYCHOLOGICAL DISTRESS; MARITAL-STATUS; SHORT-FORM; BEHAVIOR; SUPPORT; GENDER; INFORMATION; RELIABILITY; SYMPTOMS; MARRIAGE AB Objectives: Social control attempts, or attempts by social network members to influence a person's behavior, significantly predict men's health behaviors and psychological well-being. Despite the fact that depression is associated with compromised interpersonal functioning and poor health behaviors, the association between social control processes and depression has not been studied. Thus, this pilot study explored differential vulnerability to spouses' social control attempts among older, male primary care patients with varying levels of depression symptom severity and the degree to which these attempts predicted patients' behavioral and affective responses.Method: Participants included 88 older men referred by their primary care providers for a behavioral health assessment at a Veterans Affairs Medical Center. Data on sociodemographics, depressive symptomatology, health behaviors, spouses' positive and negative social control attempts, and patients' behavioral and affective responses to attempts were collected by telephone.Results: The sample was primarily Caucasian (mean age = 65.3 (SD = 8.1) years). Patients' higher depressive symptoms were significantly associated with positive and negative affective responses to their spouses' social control attempts. The frequency of control attempts and patients' behavioral responses, however, were unrelated to patients' depressive symptoms. Multiple regression models revealed that while spouses' control attempts were unrelated to patients' positive behavioral responses, more frequent negative attempts predicted greater negative behavioral responses (e.g., ignoring spouses' attempts). Moreover, negative control attempts predicted greater negative affective responses (e.g., resentment, sadness).Conclusion: The findings highlight the value of identifying effective social control strategies that maximize positive behavioral change, emotional responses, and health outcomes among older men with depressive symptoms. C1 [Mavandadi, Shahrzad; Jacques, Natacha; Sayers, Steven L.; Oslin, David W.] Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. [Mavandadi, Shahrzad; Sayers, Steven L.; Oslin, David W.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Mavandadi, S (reprint author), Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. EM shahrzad.mavandadi@va.gov FU US Department of Veterans Affairs-VISN 4 Competitive Pilot Project Fund FX This work was supported by the US Department of Veterans Affairs-VISN 4 Competitive Pilot Project Fund. The content of this article does not reflect the views of the VHA or of the Government. NR 38 TC 0 Z9 0 U1 2 U2 11 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1360-7863 EI 1364-6915 J9 AGING MENT HEALTH JI Aging Ment. Health PD NOV 2 PY 2015 VL 19 IS 11 BP 997 EP 1004 DI 10.1080/13607863.2014.986646 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA CP4JR UT WOS:000359848300005 PM 25506653 ER PT J AU Ghasemi-Rad, M Lesha, E Abkhiz, S Mohammadi, A AF Ghasemi-Rad, Mohammad Lesha, Emal Abkhiz, Saeed Mohammadi, Afshin TI PRIMARY HYPERPARATHYROIDISM: COMPARING BETWEEN SOLID AND CYSTIC ADENOMAS AND THE EFFICACY OF ULTRASOUND AND SINGLE-PHOTON EMISSION COMPUTED TOMOGRAPHY IN THEIR DIAGNOSIS SO ENDOCRINE PRACTICE LA English DT Article ID PARATHYROID ADENOMA; PREOPERATIVE LOCALIZATION; SPONTANEOUS RUPTURE; HEMATOMA; CRISIS AB Objective: Primary hyperparathyroidism (PHPT) is a disorder that results from abnormal functioning of the parathyroid glands. The purpose of this study was to compare cystic and solid adenomas by analyzing different variables associated with PHPT and parathyroid adenomas (age, calcium, phosphorus, and parathyroid hormone [PTH] levels, adenoma volume) while comparing the efficacy of ultrasound and single-photon emission computed tomography in differentiating between both types of adenoma. Methods: From 152 patients diagnosed with PHPT between January 2013 and 2014, only 109 patients who had positive ultrasonographic findings for single parathyroid adenoma were included in the study. Results: A total of 26 patients had cystic adenomas and 83 patients had solid adenomas. Sestamibi (MIBI) was negative in 50% of the cystic adenoma group and 27.7% of the solid adenoma group, with an overall technetium-MIBI efficacy of 67%. Age, phosphorus level, and adenoma volume were significantly higher in patients with cystic adenomas (P=.001, P=.02, and P=.02, respectively), whereas calcium and PTH levels were significantly higher in patients with solid adenomas (P=.02, P=.038, respectively). MIBI had a significant correlation with PTH levels (P=.031) and adenoma volume (P=.05) only in patients with solid adenomas. No significant correlation was found between sex and type of parathyroid adenoma. Conclusion: The current study is the first to compare age, PTH levels, and adenoma volume between cystic and solid adenoma patients, providing more information for the poorly understood pathology of cystic adenomas. Our findings showed that age and calcium and PTH levels are significantly higher in patients with solid adenomas, whereas adenoma volume and phosphorus levels are significantly higher in patients with cystic adenomas. C1 [Ghasemi-Rad, Mohammad] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Intervent Radiol, Boston, MA USA. [Lesha, Emal] Univ Massachusetts, Coll Sci & Math, Boston, MA 02125 USA. [Abkhiz, Saeed] Urmia Univ Med Sci, Imam Khomaini Hosp, Dept Neurol, Orumiyeh, West Azarbaijan, Iran. [Mohammadi, Afshin] Urmia Univ Med Sci, Imam Khomaini Hosp, Solid Tumor Res Ctr, Orumiyeh, West Azarbaijan, Iran. RP Mohammadi, A (reprint author), Univ Med Sci, Imam Khomaini Hosp, Solid Tumor Res Ctr, Radiol, Ershad St, Orumiyeh 5716763111, West Azarbaijan, Iran. EM afshin.mohdi@gmail.com OI Lesha, Emal/0000-0002-8902-3537 NR 22 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS PI JACKSONVILLE PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA SN 1530-891X EI 1934-2403 J9 ENDOCR PRACT JI Endocr. Pract. PD NOV PY 2015 VL 21 IS 11 BP 1277 EP 1281 DI 10.4158/EP15789.OR PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DO7MF UT WOS:000377966000010 PM 26307898 ER PT J AU Blanchard, EH Castle, S Cheng, J Roberts, C Ines, E Lee, C AF Blanchard, E. H. Castle, S. Cheng, J. Roberts, C. Ines, E. Lee, C. TI PROMOTING FITNESS AND FUNCTION AS A LIFELONG PROCESS FOR OLDER VETERANS IN GEROFIT SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Blanchard, E. H.; Castle, S.; Cheng, J.; Roberts, C.; Ines, E.; Lee, C.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Castle, S.; Lee, C.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 4 EP 4 PG 1 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222700015 ER PT J AU Dodge, HH Zhu, J Erten-Lyons, D Silbert, L Abner, EL Kryscio, R Schmitt, FA Kaye, J AF Dodge, H. H. Zhu, J. Erten-Lyons, D. Silbert, L. Abner, E. L. Kryscio, R. Schmitt, F. A. Kaye, J. TI RISK OF ALZHEIMER'S DISEASE INCIDENCE ATTRIBUTABLE TO PATHOLOGY-CONFIRMED VASCULAR DISEASE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Dodge, H. H.; Erten-Lyons, D.; Silbert, L.; Kaye, J.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Dodge, H. H.] Univ Michigan, Dept Neurol, Ann Arbor, MI USA. [Zhu, J.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Erten-Lyons, D.; Silbert, L.; Kaye, J.] Portland VA Med Ctr, Portland, OR USA. [Kryscio, R.] Univ Kentucky, Dept Biostat, Lexington, KY USA. [Kryscio, R.] Univ Kentucky, Dept Stat, Lexington, KY USA. [Abner, E. L.] Univ Kentucky, Dept Epidemiol, Lexington, KY USA. [Schmitt, F. A.] Univ Kentucky, Dept Neurol, Lexington, KY 40536 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 6 EP 6 PG 1 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222700026 ER PT J AU Atanous, AM Sherman, A Howe, JL AF Atanous, A. M. Sherman, A. Howe, J. L. TI REFLECTIVE PRACTICE ACROSS DISCIPLINES: STUDENT JOURNALING AS A LEARNING STRATEGY ABOUT THE LIFELONG PROCESS OF AGING SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Atanous, A. M.; Sherman, A.; Howe, J. L.] James J Peters VA Med Ctr, Bronx, NY USA. [Howe, J. L.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 49 EP 49 PG 1 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222700202 ER PT J AU Zhou, Y Chen, Y Musi, N AF Zhou, Y. Chen, Y. Musi, N. TI TRANSCRIPTOMIC AND METABOLOMIC ANALYSIS OF AGING MUSCLE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Zhou, Y.; Musi, N.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Musi, N.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Zhou, Y.; Musi, N.] Sam & Ann Barshop Inst Aging & Longev Studies, San Antonio, TX USA. [Chen, Y.] Greehey Childrens Canc Res Inst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 67 EP 67 PG 1 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222700262 ER PT J AU Quach, L Dugan, E Burr, JA AF Quach, L. Dugan, E. Burr, J. A. TI THE RELATIONSHIP BETWEEN CHRONIC HEALTH CONDITIONS AND FALLS: DO SOCIAL FACTORS MEDIATE THIS RELATIONSHIP AMONG COMMUNITY-DWELLING OLDER ADULTS? SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Quach, L.; Dugan, E.; Burr, J. A.] Univ Massachusettes, Boston, MA USA. [Quach, L.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 75 EP 75 PG 1 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222700286 ER PT J AU Kim, DH Patorno, E Park, Y Huybrechts, KF Levin, R Bateman, B AF Kim, D. H. Patorno, E. Park, Y. Huybrechts, K. F. Levin, R. Bateman, B. TI COMPARATIVE SAFETY OF TYPICAL AND ATYPICAL ANTIPSYCHOTICS AFTER CARDIAC SURGERY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Kim, D. H.] Beth Israel Deaconess Med Ctr, Gerontol, Boston, MA 02215 USA. [Kim, D. H.; Patorno, E.; Huybrechts, K. F.; Levin, R.; Bateman, B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Park, Y.] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Bateman, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 82 EP 82 PG 1 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222700309 ER PT J AU Kang, S Aldwin, CM Choun, S Spiro, A AF Kang, S. Aldwin, C. M. Choun, S. Spiro, A. TI A LIFESPAN/LIFE COURSE PERSPECTIVE ON COMBAT EXPOSURE: FINDINGS FROM THE VA NORMATIVE AGING STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Kang, S.] Korea Mil Acad, Seoul, South Korea. [Aldwin, C. M.; Choun, S.] Oregon State Univ, Human Dev & Family Sci, Corvallis, OR 97331 USA. [Spiro, A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Spiro, A.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Spiro, A.] Boston VA Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 118 EP 118 PG 1 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222700427 ER PT J AU Sullivan, J Shwartz, M Stolzmann, K Burgess, J Afable, M Pekoz, E Christiansen, C Berlowitz, D AF Sullivan, J. Shwartz, M. Stolzmann, K. Burgess, J. Afable, M. Pekoz, E. Christiansen, C. Berlowitz, D. TI A LONGITUDINAL ASSESSMENT OF RESIDENT-CENTERED CARE AND QUALITY IN THE DEPARTMENT OF VETERANS AFFAIRS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Sullivan, J.; Shwartz, M.; Stolzmann, K.; Burgess, J.; Afable, M.; Pekoz, E.; Christiansen, C.; Berlowitz, D.] VA Boston Healthcare Syst, CHOIR, Boston, MA USA. [Sullivan, J.; Burgess, J.; Christiansen, C.; Berlowitz, D.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Shwartz, M.; Pekoz, E.] Boston Univ, Sch Management, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 121 EP 121 PG 1 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222700437 ER PT J AU Carpenter, J Berry, PH Ersek, M AF Carpenter, J. Berry, P. H. Ersek, M. TI POST-DISCHARGE CARE IN NURSING FACILITIES AFTER HOSPITAL BASED PALLIATIVE CARE CONSULT SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Carpenter, J.] Univ Utah, Salt Lake City, UT USA. [Berry, P. H.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Ersek, M.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Ersek, M.] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 172 EP 172 PG 1 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222701089 ER PT J AU Aldwin, CM Choun, S Nath, R Proulx, J Spiro, A AF Aldwin, C. M. Choun, S. Nath, R. Proulx, J. Spiro, A. TI DOES ERYTHROCYTE SEDIMENTATION RATE COVARY WITH STRESS? LONGITUDINAL FINDINGS FROM THE VA NORMATIVE AGING STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Aldwin, C. M.; Choun, S.; Nath, R.; Proulx, J.] Oregon State Univ, Human Dev & Family Sci, Corvallis, OR 97331 USA. [Spiro, A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Spiro, A.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Spiro, A.] Boston VA Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 178 EP 179 PG 2 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222701116 ER PT J AU Lee, L Spiro, A AF Lee, L. Spiro, A. TI CHILDHOOD STRESSFUL LIFE EVENTS AND AGE TRAJECTORIES OF CARDIOMETABOLIC RISK: THE VA NORMATIVE AGING STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Lee, L.; Spiro, A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Lee, L.; Spiro, A.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Lee, L.; Spiro, A.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 179 EP 179 PG 1 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222701119 ER PT J AU Howe, JL Fernandez, H Ko, FC Ganta, N Deering, J Sun, D Dumorne, D Atanous, AM AF Howe, J. L. Fernandez, H. Ko, F. C. Ganta, N. Deering, J. Sun, D. Dumorne, D. Atanous, A. M. TI PREPARING GERIATRICS FELLOWS TO EDUCATE PRIMARY CARE PROVIDERS: A MENTORED E-LEARNING CURRICULUM DEVELOPMENT AND ASSESSMENT TRACK SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Howe, J. L.; Ko, F. C.; Sun, D.; Dumorne, D.; Atanous, A. M.] James J Peters VAMC, Bronx GRECC, Bronx, NY USA. [Howe, J. L.; Fernandez, H.; Ko, F. C.; Ganta, N.; Deering, J.] Icahn Sch Med Mt Sinai, Brookdale Dept Geriatr & Palliat Med, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 191 EP 192 PG 2 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222701158 ER PT J AU Peterson, D Dijkstra, BW Horak, FB AF Peterson, D. Dijkstra, B. W. Horak, F. B. TI THE EFFECTS OF AGE ON POSTURAL MOTOR LEARNING IN COMPENSATORY STEPPING SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Peterson, D.; Horak, F. B.] Portland VA Med Ctr, Portland, OR USA. [Peterson, D.; Horak, F. B.] Oregon Hlth & Sci Univ, Neurol, Portland, OR 97201 USA. [Dijkstra, B. W.] Univ Groningen, Groningen, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 217 EP 217 PG 1 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222701244 ER PT J AU Creekmur, B Cote, S Mitchell, MN Kramer, B AF Creekmur, B. Cote, S. Mitchell, M. N. Kramer, B. TI ACCESS TO VA HOME-BASED PRIMARY CARE EXPANSION PROGRAMS IN COLLABORATION WITH INDIAN HEALTH SERVICE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Creekmur, B.; Cote, S.; Mitchell, M. N.; Kramer, B.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Kramer, B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 256 EP 256 PG 1 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222701375 ER PT J AU Byers, AL Lai, AX Boscardin, J Nelson, JC Arean, PA Yaffe, K AF Byers, A. L. Lai, A. X. Boscardin, J. Nelson, J. C. Arean, P. A. Yaffe, K. TI PREDICTORS OF MENTAL HEALTH SERVICES USE ACROSS THE LIFESPAN SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Byers, A. L.; Boscardin, J.; Nelson, J. C.; Arean, P. A.; Yaffe, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Byers, A. L.; Lai, A. X.; Boscardin, J.; Yaffe, K.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 279 EP 280 PG 2 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222701462 ER PT J AU Rothrock, AG Bearden, D Simmons, E Booth, K Viles, A Sawyer, P Brown, CJ Flood, K AF Rothrock, A. G. Bearden, D. Simmons, E. Booth, K. Viles, A. Sawyer, P. Brown, C. J. Flood, K. TI HOURLY ROUNDING ON OLDER ADULTS IN ACUTE CARE SETTINGS: SIMULATION TRAINING FOR ACUTE CARE PROVIDERS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Rothrock, A. G.; Bearden, D.; Simmons, E.; Booth, K.; Viles, A.; Sawyer, P.; Brown, C. J.; Flood, K.] Univ Alabama Birmingham, Birmingham, AL USA. [Booth, K.; Brown, C. J.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 303 EP 303 PG 1 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222701551 ER PT J AU Hung, WW AF Hung, W. W. TI INTEGRATED CARE: ESTABLISHING CARE PLANS TO MOVE RELEVANT CLINICAL INFORMATION ACROSS SILOS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Hung, W. W.] Mt Sinai Sch Med, Geriatr, New York, NY USA. [Hung, W. W.] James J Peters VA Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 328 EP 328 PG 1 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222701648 ER PT J AU Strong, J Midden, A Mast, BT AF Strong, J. Midden, A. Mast, B. T. TI NEUROPSYCHOLOGICAL FUNCTIONING IN OLDER ADULT MUSICIANS: COGNITIVE BENEFITS OF CONTINUING TO PLAY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Strong, J.; Midden, A.; Mast, B. T.] Univ Louisville, Psychol & Brain Sci, Louisville, KY 40292 USA. [Strong, J.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 415 EP 415 PG 1 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222702130 ER PT J AU Cigolle, C Quinones, AR Nagel, CL AF Cigolle, C. Quinones, A. R. Nagel, C. L. TI INCONSISTENCY IN THE SELF-REPORT OF DIABETES IN PANEL SURVEYS: LIMITATIONS OF MEDICATION DATA IN RESOLVING PROBLEMATIC RESPONSES SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Cigolle, C.] Univ Michigan, Ann Arbor, MI 48109 USA. [Cigolle, C.] VAAAHS, GRECC, Ann Arbor, MI USA. [Quinones, A. R.; Nagel, C. L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Quinones, A. R.] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 522 EP 523 PG 2 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222702513 ER PT J AU Madigan, B Saliba, D Gassoumis, ZD Wilber, KH AF Madigan, B. Saliba, D. Gassoumis, Z. D. Wilber, K. H. TI COLLECTING CAREGIVER DATA DURING UNIVERSAL ASSESSMENT SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Madigan, B.] Univ Calif Los Angeles, VA Geriatr Social Work Educ Consortium, Los Angeles, CA USA. [Saliba, D.] Univ Calif Los Angeles, JH Borun Ctr Gerontol Res, Los Angeles, CA USA. [Saliba, D.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Saliba, D.] RAND Corp, Santa Monica, CA USA. [Gassoumis, Z. D.; Wilber, K. H.] Univ So Calif, Davis Sch Gerontol, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 535 EP 535 PG 1 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222702556 ER PT J AU Ray, LM Wilber, K Newcomer, R Fulbright, KA Saliba, D AF Ray, L. M. Wilber, K. Newcomer, R. Fulbright, K. A. Saliba, D. TI TRANSFORMING EXISTING STATE MODELS INTO AN ASSESSMENT FRAMEWORK AND RECOMMENDATIONS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Ray, L. M.; Saliba, D.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Ray, L. M.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Wilber, K.] Univ So Calif, Davis Sch Gerontol, Los Angeles, CA USA. [Newcomer, R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Fulbright, K. A.; Saliba, D.] Univ Calif Los Angeles, Borun Ctr Gerontol Res, Los Angeles, CA USA. [Saliba, D.] RAND Corp, Santa Monica, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 535 EP 535 PG 1 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222702554 ER PT J AU Wilber, K Gassoumis, ZD Fulbright, KA Ray, LM Saliba, D AF Wilber, K. Gassoumis, Z. D. Fulbright, K. A. Ray, L. M. Saliba, D. TI CALIFORNIA: WHERE ARE WE STARTING FROM? SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Wilber, K.; Gassoumis, Z. D.] Univ So Calif, Davis Sch Gerontol, Los Angeles, CA USA. [Fulbright, K. A.; Saliba, D.] Univ Calif Los Angeles, Borun Ctr Gerontol Res, Los Angeles, CA USA. [Ray, L. M.; Saliba, D.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Ray, L. M.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Saliba, D.] RAND Corp, Santa Monica, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 535 EP 535 PG 1 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222702555 ER PT J AU Allison, TA Ventura, M AF Allison, T. A. Ventura, M. TI HOW ARTS CLASSES CREATE NORMALCY IN THE CONTEXT OF NEURODEGENERATIVE DISEASE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Allison, T. A.; Ventura, M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Allison, T. A.; Ventura, M.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 546 EP 546 PG 1 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222702595 ER PT J AU Bouldin, E Trivedi, R Reiber, GE Nelson, K AF Bouldin, E. Trivedi, R. Reiber, G. E. Nelson, K. TI DO CAREGIVERS IMPROVE SELF-CARE AMONG ADULTS WITH POORLY CONTROLLED DIABETES? SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Bouldin, E.; Reiber, G. E.; Nelson, K.] VA Puget Sound, HSR&D, Seattle, WA USA. [Bouldin, E.; Reiber, G. E.; Nelson, K.] Univ Washington, Seattle, WA 98195 USA. [Trivedi, R.] VA Palo Alto Hlth Care Syst, Menlo Pk, CA USA. [Trivedi, R.] Stanford Univ, Palo Alto, CA 94304 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 652 EP 652 PG 1 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222703156 ER PT J AU LaRocca, MA Scogin, F Lichstein, KL Mieskowski, L Moran, C Woosley, JA DiNapoli, EA Thomas, SJ AF LaRocca, M. A. Scogin, F. Lichstein, K. L. Mieskowski, L. Moran, C. Woosley, J. A. DiNapoli, E. A. Thomas, S. J. TI PREDICTORS OF QUALITY OF LIFE AMONG RURAL OLDER ADULTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [LaRocca, M. A.; Scogin, F.; Lichstein, K. L.; Mieskowski, L.; Moran, C.; Woosley, J. A.] Univ Alabama, Clin Psychol, Tuscaloosa, AL USA. [DiNapoli, E. A.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Thomas, S. J.] AL VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 681 EP 681 PG 1 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222703254 ER PT J AU Kramer, B Frank, JC Creekmur, B Melendez, L Douglas, J Lee, D Mitchell, MN AF Kramer, B. Frank, J. C. Creekmur, B. Melendez, L. Douglas, J. Lee, D. Mitchell, M. N. TI THE IMPACT OF THE VA GERIATRIC SCHOLARS PROGRAM: INTEGRATING GERIATRICS IN PRIMARY CARE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Kramer, B.; Creekmur, B.; Melendez, L.; Douglas, J.; Lee, D.; Mitchell, M. N.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Kramer, B.; Frank, J. C.] Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 716 EP 716 PG 1 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222703371 ER PT J AU Kirn, DR Reid, KF Hau, C Phillips, E Fielding, R AF Kirn, D. R. Reid, K. F. Hau, C. Phillips, E. Fielding, R. TI WHAT IS A CLINICALLY MEANINGFUL CHANGE IN LOWER EXTREMITY POWER FOR MOBILITY-LIMITED OLDER ADULTS? SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Kirn, D. R.; Reid, K. F.; Hau, C.; Phillips, E.; Fielding, R.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Nutr Exercise Physiol & Sarcopenia Lab, Boston, MA 02111 USA. [Phillips, E.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. [Phillips, E.] Joslin Diabet Ctr, Inst Lifestyle Med, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 734 EP 734 PG 1 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222703440 ER PT J AU Huh, J Gould, CE Shah, S Brown, K AF Huh, J. Gould, C. E. Shah, S. Brown, K. TI INCREASING SOCIALIZATION AND REDUCING LONELINESS IN OLDER RURAL VETERANS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Huh, J.; Gould, C. E.] VA Palo Alto Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Palo Alto, CA USA. [Huh, J.; Gould, C. E.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Shah, S.] VA Puget Sound Hlth Care Syst, Tacoma, WA USA. [Brown, K.] Episcopal Senior Communities, Oakland, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 815 EP 816 PG 2 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222704234 ER PT J AU Trivedi, R Slightam, C Piette, JD Nelson, K Rosland, A Heidenreich, P Asch, S Timko, C AF Trivedi, R. Slightam, C. Piette, J. D. Nelson, K. Rosland, A. Heidenreich, P. Asch, S. Timko, C. TI SUCCEED: A PILOT STUDY OF A HEART FAILURE SELF-MANAGEMENT PROGRAM FOR COUPLES SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Trivedi, R.; Slightam, C.; Heidenreich, P.; Asch, S.; Timko, C.] VA Palo Alto Hlth Care Syst, Menlo Pk, CA USA. [Trivedi, R.; Heidenreich, P.; Asch, S.; Timko, C.] Stanford Univ, Stanford, CA 94305 USA. [Piette, J. D.; Rosland, A.] Ann Arbor VA, Ann Arbor, VA USA. [Piette, J. D.; Rosland, A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Nelson, K.] VA Puget Sound HCS, Seattle, WA USA. [Nelson, K.] Univ Washington, Seattle, WA 98195 USA. RI Rosland, Annmarie/B-7750-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 822 EP 823 PG 2 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222704263 ER PT J AU Gerolimatos, LA Page, KS Hinrichs, KL Balestracci, P Concepcion, C AF Gerolimatos, L. A. Page, K. S. Hinrichs, K. L. Balestracci, P. Concepcion, C. TI EVALUATING THE USEFULNESS OF A DEMENTIA CARE TRAINING PROGRAM IN A VA COMMUNITY LIVING CENTER SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Gerolimatos, L. A.; Hinrichs, K. L.; Balestracci, P.; Concepcion, C.] VA Boston Healthcare Syst, Brockton, MA USA. [Page, K. S.] Cheyenne VA Med Ctr, Cheyenne, WY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 BP 828 EP 828 PG 1 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222704287 ER PT J AU Apelo, SA Lamming, D AF Apelo, Sebastian Arriola Lamming, Dudley TI Alternative Rapamycin Treatment Regimens Promote Longevity While Minimizing Side Effects SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Wisconsin, Med, Madison, WI 53706 USA. William S Middleton Mem VA Hosp, Madison, WI USA. [Apelo, Sebastian Arriola; Lamming, Dudley] Univ Wisconsin, William S Middleton Mem Vet Adm Hosp, Med, Madison, WI 53706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 MA 340 PG 1 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222704460 ER PT J AU Cortes, J Shrestha, S Ramos, K Cummings, J Armento, M Kunik, ME Stanley, MA Bush, A AF Cortes, Jose Shrestha, Srijana Ramos, Katherine Cummings, Jeremy Armento, Maria Kunik, Mark E. Stanley, Melinda A. Bush, Amy TI Psychometric Properties of Worry/Anxiety Measures in an Urban, Racially Diverse, Underserved Sample of Older Adults SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Cortes, Jose; Shrestha, Srijana; Armento, Maria; Kunik, Mark E.; Stanley, Melinda A.; Bush, Amy] Baylor Coll Med, Psychiat & Behav Sci, Houston, TX 77030 USA. [Cortes, Jose; Kunik, Mark E.; Stanley, Melinda A.; Bush, Amy] Houston VA Med Ctr, HSR&D, Houston, TX USA. [Shrestha, Srijana] Univ St Thomas, Psychol, St Paul, MN USA. [Ramos, Katherine] Durham VA Med Ctr, GRECC, Durham, NC USA. [Cummings, Jeremy] Southeastern Univ, Lakeland, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 MA 332 PG 1 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222704508 ER PT J AU Perez, K Ramos, K Wilson, NL Bush, A Kunik, ME Stanley, MA AF Perez, Kateri Ramos, Katherine Wilson, Nancy L. Bush, Amy Kunik, Mark E. Stanley, Melinda A. TI Vida Calma: Spanish-adapted CBT intervention for Spanish Elder with GAD SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Perez, Kateri] Univ Houston, Psychol Hlth & Learning Sci, Houston, TX 77004 USA. [Perez, Kateri; Wilson, Nancy L.; Bush, Amy; Kunik, Mark E.; Stanley, Melinda A.] Houston VA Med Ctr, HSR & D, Houston, TX USA. [Perez, Kateri; Wilson, Nancy L.; Bush, Amy; Kunik, Mark E.; Stanley, Melinda A.] Baylor Coll Med, Psychiat & Behav Sci, Houston, TX 77030 USA. [Ramos, Katherine] Durham VA Med Ctr, GRECC, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 MA 359 PG 2 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222704479 ER PT J AU Rogus-Pulia, N Zielinski, JJ Rusche, N Divyak, E Gangnon, R Safdar, N Robbins, J AF Rogus-Pulia, Nicole Zielinski, Jill J. Rusche, Nicole Divyak, Elizabeth Gangnon, Ronald Safdar, Nasia Robbins, Joanne TI Outcomes from the Swallow STRengthening OropharyNGeal (Swallow STRONG) Program and Expansion sites: An Update SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Rogus-Pulia, Nicole; Zielinski, Jill J.; Rusche, Nicole; Divyak, Elizabeth; Safdar, Nasia; Robbins, Joanne] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. [Rogus-Pulia, Nicole; Robbins, Joanne] Univ Wisconsin, Med, Madison, WI 53706 USA. [Gangnon, Ronald] Univ Wisconsin, Biostat & Med Informat, Madison, WI 53706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 MA 342 PG 1 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222704462 ER PT J AU Syme, M Caalaman, E Lichtenberg, PA Moye, J AF Syme, Maggie Caalaman, Erwin Lichtenberg, Peter A. Moye, Jennifer TI Sexuality and Consent in Long-term Care: Assessment Development through Expert Consensus SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Syme, Maggie] Kansas State Univ, Ctr Aging, Manhattan, KS 66506 USA. [Caalaman, Erwin] Univ San Diego, Psychol Sci, San Diego, CA 92110 USA. [Lichtenberg, Peter A.] Wayne State Univ, Detroit, MI 48202 USA. [Moye, Jennifer] VA Boston Healthcare Syst, Boston, MA USA. RI Moye, Jennifer/F-2240-2017 OI Moye, Jennifer/0000-0002-3434-347X NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 MA 338 PG 2 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222704627 ER PT J AU Thorpe, C Fowler, N Zhao, XH Harrigan, K Kang, YH Thorpe, JM Hanlon, JT Gellad, WF AF Thorpe, Carolyn Fowler, Nicole Zhao, Xinhua Harrigan, Katherine Kang, Yihuang Thorpe, Joshua M. Hanlon, Joseph T. Gellad, Walid F. TI Initiation and Discontinuation of Antidementia Drugs in a National Sample of Medicare Beneficiaries SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Thorpe, Carolyn; Harrigan, Katherine; Thorpe, Joshua M.] Univ Pittsburgh, Pharm & Therapeut, Pittsburgh, PA 15260 USA. [Thorpe, Carolyn; Zhao, Xinhua; Thorpe, Joshua M.; Hanlon, Joseph T.; Gellad, Walid F.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Fowler, Nicole] Indiana Univ Sch Med, Gen Internal Med, Indianapolis, IN 46202 USA. [Zhao, Xinhua; Kang, Yihuang; Hanlon, Joseph T.; Gellad, Walid F.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD NOV PY 2015 VL 55 SU 2 MA 343 PG 2 WC Gerontology SC Geriatrics & Gerontology GA DJ5BV UT WOS:000374222704519 ER PT J AU Arias, JJ Pham-Kanter, G Gonzalez, R Campbell, EG AF Arias, Jalayne J. Pham-Kanter, Genevieve Gonzalez, Rosa Campbell, Eric G. TI Trust, vulnerable populations, and genetic data sharing SO JOURNAL OF LAW AND THE BIOSCIENCES LA English DT Article DE Data Sharing; genetic; genomic; research; policy; scientific norms AB Recent policies and proposed regulations, including the Notice of Proposed Rulemaking for the Common Rule and the 2014 NIH Genetic Data Sharing Policy, seek to improve research subject protections. Protections for subjects whose genetic data is shared are critical to reduce risks such as loss of confidentiality, stigma, and discrimination. In the article 'It depends whose data are being shared: considerations for genomic data sharing policies', Robinson et al. provide a response to our article, 'The Growth and Gaps of Genetic Data Sharing Policies'. Robinson et al. highlight the importance of individual and group preferences. In this article, we extend the conversation on models for improving protections which will mitigate consequences for individuals and groups that are vulnerable to stigma and discrimination. C1 [Arias, Jalayne J.; Gonzalez, Rosa] Cleveland Clin, Dept Bioeth, Cleveland, OH 44195 USA. [Pham-Kanter, Genevieve] Drexel Univ, Sch Publ Hlth, Dept Hlth Management & Policy, Philadelphia, PA USA. [Campbell, Eric G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Campbell, Eric G.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Arias, JJ (reprint author), Cleveland Clin, Dept Bioeth, Cleveland, OH 44195 USA. EM ariasj@ccf.org OI Pham-Kanter, Genevieve/0000-0002-3044-7829 FU NHGRI NIH HHS [R01 HG006281] NR 15 TC 0 Z9 0 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 2053-9711 J9 J LAW BIOSCI JI J. Law Biosci. PD NOV PY 2015 VL 2 IS 3 BP 747 EP 753 DI 10.1093/jlb/lsv044 PG 7 WC Law SC Government & Law GA DJ8XO UT WOS:000374497800019 PM 27774227 ER PT J AU Hegazi, R El-Gamal, M Abdel-Hady, N Hamdy, O AF Hegazi, Refaat El-Gamal, Mohamed Abdel-Hady, Nagy Hamdy, Osama TI Epidemiology of and Risk Factors for Type 2 Diabetes in Egypt SO ANNALS OF GLOBAL HEALTH LA English DT Review DE diabetes; Egypt; hepatitis C infection; MENA; obesity; pesticide ID HEPATITIS-C VIRUS; INSULIN-RESISTANCE; DEVELOPMENTAL EXPOSURE; CHLORPYRIFOS; PESTICIDE; MELLITUS; PREVALENCE; METABOLISM; INFECTION; MALATHION AB BACK GROUND Diabetes is a fast-growing health problem in Egypt with a significant impact on morbidity, mortality, and health care resources. Currently, the prevalence of type 2 diabetes (T2D) in Egypt is around 15.6% of all adults aged 20 to 79. OBJECTIVE To describe the epidemiology, principal causes, associated risk factors, cultural aspects, and challenges that may contribute to the rapid rise in T2D in Egypt. METHODS Review of papers in PubMed and relevant gray literature. FINDINGS The International Diabetes Federation (IDF) has identified Egypt as the ninth leading country in the world for the number of patients with T2D. The prevalence of T2D in Egypt was almost tripled over the last 2 decades. This sharp rise could be attributed to either an increased pattern of the traditional risk factors for T2D such as obesity and physical inactivity and change in eating pattern or other risk factors unique to Egypt. These include increased exposure to environmental risk factors like pesticides and increased prevalence of chronic hepatitis C. CONCLUSIONS Prevention, early identification, and effective intervention are integral components of effective T2D care in Egypt. These strategies may reduce the expanding economic burden associated with T2D care. C1 [Hegazi, Refaat] Abbott Nutr Res & Dev, Columbus, OH USA. [El-Gamal, Mohamed] Mansoura Univ, Fac Med, Dept Toxicol, Mansoura, Egypt. [El-Gamal, Mohamed] Mansoura Univ, Med Expt Res Ctr, Mansoura, Egypt. [Abdel-Hady, Nagy] Mansoura Univ, Fac Med, Dept Internal Med, Mansoura, Egypt. [Hamdy, Osama] Joslin Diabet Ctr, Boston, MA 02215 USA. RP Hegazi, R (reprint author), Abbott Nutr Res & Dev, Columbus, OH USA. EM Refaat.Hegazi@abbott.com FU Metagenics Inc FX Osama Hamdy is receiving research support from Metagenics Inc and is on the advisory board of Merck Inc, Astra-Zeneca Inc, Boehringer Ingelheim Inc, and Abbott Nutrition. Refaat Hegazi is a full time employee of Abbott Nutrition Research & Development. The material presented in this article is based on the best-known clinical evidence and is not affected by this financial relationship. NR 29 TC 1 Z9 1 U1 3 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2214-9996 J9 ANN GLOB HEALTH JI Ann. Glob. Health PD NOV-DEC PY 2015 VL 81 IS 6 BP 814 EP 820 DI 10.1016/j.aogh.2015.12.011 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DK9AP UT WOS:000375222200009 PM 27108148 ER PT J AU Braunstein, LZ Chen, MH Dosoretz, DE Salenius, S Katin, M Nanda, A D'Amico, AV AF Braunstein, L. Z. Chen, M. H. Dosoretz, D. E. Salenius, S. Katin, M. Nanda, A. D'Amico, A. V. TI Whole-Pelvis Versus Prostate-Only Radiation Therapy and Androgen Deprivation Therapy: Effects on Mortality Risk SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Braunstein, L. Z.] Harvard Radiat Oncol Program, Boston, MA USA. [Chen, M. H.] Univ Connecticut, Storrs, CT USA. [Dosoretz, D. E.; Salenius, S.; Katin, M.] 21st Century Oncol, Ft Myers, FL USA. [Nanda, A.] Orlando Hlth, UF Hlth Canc Ctr, Orlando, FL USA. [D'Amico, A. V.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2483 BP E190 EP E191 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300483 ER PT J AU Braunstein, SE Gunther, JR Spektor, A Falit, B Mirabeau-Beale, KL Young, K Brower, JV Mancini, BR Ye, JC Rajagopalan, MS Du, KL Rao, YJ Hara, W Currey, AD Jimenez, RB Golden, DW AF Braunstein, S. E. Gunther, J. R. Spektor, A. Falit, B. Mirabeau-Beale, K. L. Young, K. Brower, J. V. Mancini, B. R. Ye, J. C. Rajagopalan, M. S. Du, K. L. Rao, Y. J. Hara, W. Currey, A. D. Jimenez, R. B. Golden, D. W. TI Role of the Resident as a Teacher (RAT) in the Medical Student (MS) Clerkship: A Report From the Radiation Oncology Education Collaborative Study Group SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Braunstein, S. E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Gunther, J. R.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Spektor, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Falit, B.] Harvard Radiat Oncol Program, Boston, MA USA. [Mirabeau-Beale, K. L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Young, K.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Brower, J. V.] Univ Wisconsin, Madison, WI USA. [Mancini, B. R.] Yale Univ, Sch Med, New Haven, CT USA. [Ye, J. C.] Weill Cornell Med Ctr, NewYork Presbyterian, New York, NY USA. [Rajagopalan, M. S.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Du, K. L.] NYU, Langone Med Ctr, New York, NY USA. [Rao, Y. J.] Washington Univ, St Louis, MO USA. [Hara, W.] Stanford Univ, Stanford, CA 94305 USA. [Currey, A. D.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Jimenez, R. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Golden, D. W.] Univ Chicago, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2945 BP E379 EP E379 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301014 ER PT J AU Buzurovic, I Damato, AL Studenski, MT Deufel, CL Huang, J Gaffney, DK Hayeon, K Scanderbeg, DJ Bosch, WR Erickson, BA Viswanathan, AN AF Buzurovic, I. Damato, A. L. Studenski, M. T. Deufel, C. L. Huang, J. Gaffney, D. K. Hayeon, K. Scanderbeg, D. J. Bosch, W. R. Erickson, B. A. Viswanathan, A. N. TI Dosimetric Evaluations of CT and MR-Based Brachytherapy Treatment Plans for Cervical Cancers Using Consensus Contouring Atlases SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Buzurovic, I.; Damato, A. L.; Viswanathan, A. N.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Studenski, M. T.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Deufel, C. L.] Mayo Clin, Rochester, MN USA. [Huang, J.; Gaffney, D. K.] Univ Utah, Huntsman Canc Hosp, Salt Lake City, UT USA. [Hayeon, K.] Univ Pittsburgh, Magee Womens Hosp, Med Ctr, Pittsburgh, PA 15213 USA. [Scanderbeg, D. J.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Bosch, W. R.] Washington Univ, Sch Med, St Louis, MO USA. [Erickson, B. A.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2704 BP E282 EP E283 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300700 ER PT J AU Cahlon, O Ho, AY Siu, CT McCormick, B Recht, A Taghian, AG Powell, SN AF Cahlon, O. Ho, A. Y. Siu, C. T. McCormick, B. Recht, A. Taghian, A. G. Powell, S. N. TI A Phase II Study of Once a Day Partial Breast Irradiation (PBI) for Early-Stage or Noninvasive Breast Cancer: Early Toxicity Outcomes SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Cahlon, O.; Ho, A. Y.; Siu, C. T.; McCormick, B.; Powell, S. N.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Recht, A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Taghian, A. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2036 BP E15 EP E15 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300038 ER PT J AU Cho, LP Manuel, M Damato, AL Lee, LJ Viswanathan, AN AF Cho, L. P. Manuel, M. Damato, A. L. Lee, L. J. Viswanathan, A. N. TI Prognostic Factors in Computed Tomographye-Guided Brachytherapy for Stage I-II Cervical Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Cho, L. P.; Manuel, M.; Damato, A. L.; Lee, L. J.; Viswanathan, A. N.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Cho, L. P.; Manuel, M.; Damato, A. L.; Lee, L. J.; Viswanathan, A. N.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2706 BP E283 EP E284 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300702 ER PT J AU Choi, NC Gainor, J Ackman, J Lim, R Sharp, GC El Fakhri, G Niemierko, A AF Choi, N. C. Gainor, J. Ackman, J. Lim, R. Sharp, G. C. El Fakhri, G. Niemierko, A. TI Improved Local Tumor Control With Supplementary Dose of Radiation Guided by F-18-FDG PET Soon After Standard Dose Radiation Therapy and Concurrent Chemotherapy in Inoperable Stages II and III Non-Small Cell Lung Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Choi, N. C.; Gainor, J.; Ackman, J.; Lim, R.; Sharp, G. C.; El Fakhri, G.; Niemierko, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 3093 BP E438 EP E439 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301161 ER PT J AU Chowdhry, VK Goldberg, S Liu, L Adams, JA Bernstein, K Liebsch, NJ Niemierko, A DeLaney, TF AF Chowdhry, V. K. Goldberg, S. Liu, L. Adams, J. A. Bernstein, K. Liebsch, N. J. Niemierko, A. DeLaney, T. F. TI Thoracolumbar Spinal Cord Tolerance to High-Dose Conformal Proton- Photon Radiation Therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Chowdhry, V. K.; Goldberg, S.; Liu, L.; Adams, J. A.; Bernstein, K.; Niemierko, A.; DeLaney, T. F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Liebsch, N. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 3294 BP E516 EP E517 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301360 ER PT J AU Dagoglu, RN Catalano, PJ Mahadevan, A Martin, NE Hong, TS Wo, JY Nedea, EA Kimmelman, AC Mamon, HJ AF Dagoglu, R. N. Catalano, P. J. Mahadevan, A. Martin, N. E. Hong, T. S. Wo, J. Y. Nedea, E. A. Kimmelman, A. C. Mamon, H. J. TI Lymph Node Retrieval Following Neoadjuvant Therapy in Patients With Rectal Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Dagoglu, R. N.] Istanbul Fac Med, Dept Radiat Oncol, Istanbul, Turkey. [Dagoglu, R. N.; Mahadevan, A.; Nedea, E. A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Catalano, P. J.; Martin, N. E.; Kimmelman, A. C.; Mamon, H. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hong, T. S.; Wo, J. Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2436 BP E171 EP E171 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300436 ER PT J AU Dinh, TKT Fendler, W Chalubinska-Fendler, JP Acharya, SS O'Leary, C Deraska, PV Chowdhury, D D'Andrea, AD Kozono, DE AF Dinh, T. K. T. Fendler, W. Chalubinska-Fendler, J. P. Acharya, S. S. O'Leary, C. Deraska, P. V. Chowdhury, D. D'Andrea, A. D. Kozono, D. E. TI Circulating MicroRNA Profiling for Thoracic Radiation Therapy Biomarkers SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Dinh, T. K. T.; Kozono, D. E.] Harvard Univ, Sch Med, Boston, MA USA. [Dinh, T. K. T.; O'Leary, C.; Deraska, P. V.; Chowdhury, D.; D'Andrea, A. D.; Kozono, D. E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fendler, W.; Chalubinska-Fendler, J. P.] Med Univ Lodz, Lodz, Poland. [Acharya, S. S.; Chowdhury, D.] Harvard Univ, Cambridge, MA 02138 USA. RI Fendler, Wojciech/S-9592-2016 OI Fendler, Wojciech/0000-0002-5083-9168 NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 3277 BP E510 EP E510 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301343 ER PT J AU Elmore, SN Balboni, TA AF Elmore, S. N. Balboni, T. A. TI Symptom Control and Predictors of Survival in Leptomeningeal Carcinomatosis of the Neuroaxis Treated With Radiation Therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Elmore, S. N.; Balboni, T. A.] Harvard Univ, Sch Med, Boston, MA USA. [Balboni, T. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 3195 BP E478 EP E479 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301262 ER PT J AU Golden, DW Spektor, A Gunther, JR Thaker, NG Braunstein, SE Young, K Bornstein, S Hung, AY Brower, JV Mohindra, P Mancini, BR Ye, JC Rajagopalan, MS Du, KL Rao, YJ Gibbs, IC Hara, W Kharofa, JR Currey, AD Jimenez, RB AF Golden, D. W. Spektor, A. Gunther, J. R. Thaker, N. G. Braunstein, S. E. Young, K. Bornstein, S. Hung, A. Y. Brower, J. V. Mohindra, P. Mancini, B. R. Ye, J. C. Rajagopalan, M. S. Du, K. L. Rao, Y. J. Gibbs, I. C. Hara, W. Kharofa, J. R. Currey, A. D. Jimenez, R. B. TI Evaluation of a Multi-institutional Radiation Oncology Clerkship Curriculum: A Report From the Radiation Oncology Education Collaborative Study Group SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Golden, D. W.] Univ Chicago, Chicago, IL 60637 USA. [Spektor, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gunther, J. R.; Thaker, N. G.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Braunstein, S. E.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Young, K.; Bornstein, S.; Hung, A. Y.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Brower, J. V.] Univ Wisconsin, Madison, WI USA. [Mohindra, P.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Mancini, B. R.] Yale Univ, Sch Med, New Haven, CT USA. [Ye, J. C.] Weill Cornell Med Ctr, NewYork Presbyterian, New York, NY USA. [Rajagopalan, M. S.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Du, K. L.] NYU, Langone Med Ctr, New York, NY USA. [Rao, Y. J.] Washington Univ, St Louis, MO USA. [Gibbs, I. C.] Stanford Canc Inst, Stanford, CA USA. [Hara, W.] Stanford Univ, Stanford, CA 94305 USA. [Kharofa, J. R.] Univ Cincinnati, Cincinnati, OH USA. [Currey, A. D.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Jimenez, R. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2937 BP E376 EP E376 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301006 ER PT J AU Goyal, A Carter, J Pashtan, IM Gallotto, S Niemierko, A Ng, AK Winkfield, KM AF Goyal, A. Carter, J. Pashtan, I. M. Gallotto, S. Niemierko, A. Ng, A. K. Winkfield, K. M. TI Low Dose Versus High Dose Radiation Therapy for Indolent Primary Cutaneous B-Cell Lymphomas SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Goyal, A.] Harvard Univ, Sch Med, Boston, MA USA. [Carter, J.; Gallotto, S.; Niemierko, A.; Winkfield, K. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pashtan, I. M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ng, A. K.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 3137 BP E455 EP E455 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301204 ER PT J AU Grassberger, C Manem, V Eaton, BR Yock, TI Paganetti, H AF Grassberger, C. Manem, V. Eaton, B. R. Yock, T. I. Paganetti, H. TI Predicting Secondary Breast and Lung Malignancy Risk After Combined Chemoradiation Treatment SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Grassberger, C.; Manem, V.; Eaton, B. R.; Yock, T. I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Manem, V.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Paganetti, H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 3270 BP E508 EP E508 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301337 ER PT J AU Greenberger, JS Shinde, A Berhane, H Dixon, T Franicola, D Li, S Kagan, V Parmar, K Guinan, E Epperly, M AF Greenberger, J. S. Shinde, A. Berhane, H. Dixon, T. Franicola, D. Li, S. Kagan, V. Parmar, K. Guinan, E. Epperly, M. TI Mitochondrial Localization of GS-Nitroxide JP4-039 Delivered in Intraoral Emulsion Ameliorates Radiation Mucositis in Fanconi Anemia (FA) Fancd2-/- Mice SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Greenberger, J. S.] Univ Pittsburgh, Dept Radiat Oncol, Inst Canc, Pittsburgh, PA USA. [Shinde, A.; Berhane, H.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Dixon, T.; Franicola, D.; Li, S.; Kagan, V.; Epperly, M.] Univ Pittsburgh, Pittsburgh, PA USA. [Parmar, K.; Guinan, E.] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 3356 BP E540 EP E541 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301421 ER PT J AU Gutt, R Malhotra, S Jolly, S Moghanaki, D Cheuk, AV Fosmire, H Kelly, MD Hoffman-Hogg, L Lutz, S Anscher, MS Dawson, GA AF Gutt, R. Malhotra, S. Jolly, S. Moghanaki, D. Cheuk, A. V. Fosmire, H. Kelly, M. D. Hoffman-Hogg, L. Lutz, S. Anscher, M. S. Dawson, G. A. TI Management of Metastatic Spinal Cord Compression Among Veterans Health Administration Radiation Oncologists SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Gutt, R.] Washington DC VA Med Ctr, Washington, DC USA. [Malhotra, S.; Cheuk, A. V.; Dawson, G. A.] James J Peters VA Med Ctr, Bronx, NY USA. [Jolly, S.] Univ Michigan, Ann Arbor, MI 48109 USA. [Moghanaki, D.; Anscher, M. S.] Virginia Commonwealth Univ, Med Ctr, Richmond, VA USA. [Moghanaki, D.] Hunter Holmes McGuire VA Med Ctr, Richmond, VA USA. [Fosmire, H.] Roudebush VA Med Ctr, Indianapolis, IN USA. [Kelly, M. D.] VA New Jersey Hlth Care Syst, E Orange, NJ USA. [Hoffman-Hogg, L.] Albany Stratton VA Med Ctr, Albany, NY USA. [Lutz, S.] Blanchard Valley Reg Canc Ctr, Findlay, OH USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 3189 BP E475 EP E476 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301256 ER PT J AU Holliday, E Wood, LJ Dieckmann, N Thomas, CR AF Holliday, E. Wood, L. J. Dieckmann, N. Thomas, C. R., Jr. TI Relationship Between Fatigue, Sleep Quality, and Cytokines During External Beam Radiation Therapy for Prostate Cancer: A Phase 2 Study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Holliday, E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Wood, L. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dieckmann, N.] Oregon Heath & Sci Univ, Portland, OR USA. [Thomas, C. R., Jr.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2484 BP E191 EP E191 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300484 ER PT J AU Huynh, MA Maire, CL Abazeed, M Adams, D Pelton, K Pinnell, N Ramkissoon, S Korideck, H Van Hummelen, P Thorner, A Wen, P Ligon, AH Schreiber, S Meyerson, M Ligon, KL Alexander, BM AF Huynh, M. A. Maire, C. L. Abazeed, M. Adams, D. Pelton, K. Pinnell, N. Ramkissoon, S. Korideck, H. Van Hummelen, P. Thorner, A. Wen, P. Ligon, A. H. Schreiber, S. Meyerson, M. Ligon, K. L. Alexander, B. M. TI Functional Profiling of a Glioblastoma (GBM) Patient-Derived Cell Line (PDCL) Panel Identifies Cell-Intrinsic Differential Radiation Response That Correlates With TP53 Mutations SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Huynh, M. A.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Maire, C. L.; Pelton, K.; Pinnell, N.; Korideck, H.; Van Hummelen, P.; Thorner, A.; Meyerson, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Abazeed, M.] Cleveland Clin, Cleveland, OH 44106 USA. [Adams, D.; Meyerson, M.] Broad Inst, Cambridge, MA USA. [Ramkissoon, S.; Ligon, A. H.; Ligon, K. L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wen, P.; Alexander, B. M.] Brigham & Womens Canc Ctr, Dana Farber Canc Inst, Boston, MA USA. [Schreiber, S.] MIT, Cambridge, MA 02139 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2232 BP E91 EP E92 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300232 ER PT J AU Hwang, W Marciscano, AE Kim, D Stemmer-Rachamimov, AO Curry, WT Barker, FG Larvie, M Shih, HA AF Hwang, W. Marciscano, A. E. Kim, D. Stemmer-Rachamimov, A. O. Curry, W. T. Barker, F. G., II Larvie, M. Shih, H. A. TI Correlation of Imaging Characteristics With Histopathological WHO Grade in Meningiomas SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Hwang, W.; Kim, D.] Harvard Univ, Sch Med, Boston, MA USA. [Marciscano, A. E.] Johns Hopkins Univ, Baltimore, MD USA. [Stemmer-Rachamimov, A. O.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Curry, W. T.; Barker, F. G., II] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Larvie, M.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Shih, H. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2218 BP E86 EP E86 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300218 ER PT J AU Hyder, J Boggs, H Chuong, MD Suntharalingam, M Burrows, W Horiba, N Zandberg, DP Tyer, TN Cohen, EP Vujaskovic, Z Mohindra, P AF Hyder, J. Boggs, H. Chuong, M. D. Suntharalingam, M. Burrows, W. Horiba, N. Zandberg, D. P. Tyer, T. N. Cohen, E. P. Vujaskovic, Z. Mohindra, P. TI Impact of Incidental Angiotensin Converting Enzyme Inhibitor (ACEi) and Angiotensin Receptor Blocker (ARB) Use on Pathologic Complete Response (pCR) to Neoadjuvant Chemoradiation (NA-CRT) in Esophageal Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Hyder, J.; Boggs, H.; Tyer, T. N.] Univ Maryland, Sch Med, Dept Radiat Oncol, Baltimore, MD 21201 USA. [Chuong, M. D.; Suntharalingam, M.; Burrows, W.; Vujaskovic, Z.; Mohindra, P.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Horiba, N.; Zandberg, D. P.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Cohen, E. P.] Med Coll Wisconsin, Dept Nephrol, Milwaukee, WI 53226 USA. [Cohen, E. P.] US Dept Vet Affairs, Milwaukee, WI USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2390 BP E153 EP E154 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300390 ER PT J AU Jiang, G Balboni, TA Taylor, A Viswanathan, AN Lee, LJ AF Jiang, G. Balboni, T. A. Taylor, A. Viswanathan, A. N. Lee, L. J. TI Clinical Predictors of Response to Palliative Radiation Therapy for Recurrent Ovarian Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Jiang, G.; Balboni, T. A.; Lee, L. J.] Harvard Univ, Sch Med, Boston, MA USA. [Balboni, T. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Taylor, A.; Viswanathan, A. N.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lee, L. J.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2671 BP E269 EP E270 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300669 ER PT J AU Kabolizadeh, P Chen, YLE Liebsch, NJ Hornicek, FJ Schwab, J Choy, E Rosenthal, DI DeLaney, TF AF Kabolizadeh, P. Chen, Y. L. E. Liebsch, N. J. Hornicek, F. J. Schwab, J. Choy, E. Rosenthal, D. I. DeLaney, T. F. TI Analysis of Tumor Response in Mobile Spine and Sacral Chordoma Treated With Definitive High Dose Photon/Proton Radiation Therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Kabolizadeh, P.; Chen, Y. L. E.; Liebsch, N. J.; Hornicek, F. J.; Schwab, J.; Choy, E.; Rosenthal, D. I.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [DeLaney, T. F.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 3596 BP E636 EP E637 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301658 ER PT J AU Kamran, SC Mueller, B Paetzold, P Dunlap, J Bortfeld, T Willers, H Craft, D AF Kamran, S. C. Mueller, B. Paetzold, P. Dunlap, J. Bortfeld, T. Willers, H. Craft, D. TI Multicriteria Optimization (MCO) Achieves Superior Normal Tissue Sparing By Intensity Modulated Radiation Therapy (IMRT) in Lung Cancer Patients Using RTOG 1308 Guidelines SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Kamran, S. C.] Harvard Univ, Radiat Oncol Program, Boston, MA 02115 USA. [Mueller, B.] Tech Univ Munich, Klinikum Rechts Isar, Dept Radiat Oncol, D-80290 Munich, Germany. [Mueller, B.] Tech Univ Munich, Phys Dept, D-80290 Munich, Germany. [Paetzold, P.; Dunlap, J.; Bortfeld, T.; Craft, D.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Willers, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 3398 BP E556 EP E557 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301462 ER PT J AU Kamran, SC Russo, AL Borger, DR Szymonifka, J Kwak, EL Clark, JW Blaszkowsky, LS Ryan, DP Allen, JN Wo, JY Zhu, AX Iafrate, A Haigis, KM Hong, TS AF Kamran, S. C. Russo, A. L. Borger, D. R. Szymonifka, J. Kwak, E. L. Clark, J. W. Blaszkowsky, L. S. Ryan, D. P. Allen, J. N. Wo, J. Y. Zhu, A. X. Iafrate, A. Haigis, K. M. Hong, T. S. TI Influence of Body Mass Index (BMI) on Colorectal Cancer Mutation Status SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Kamran, S. C.] Harvard Radiat Oncol Program, Boston, MA USA. [Russo, A. L.; Borger, D. R.; Szymonifka, J.; Kwak, E. L.; Clark, J. W.; Blaszkowsky, L. S.; Ryan, D. P.; Allen, J. N.; Zhu, A. X.; Iafrate, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wo, J. Y.; Hong, T. S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Haigis, K. M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2393 BP E155 EP E155 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300393 ER PT J AU Keane, FK Wo, JY Wolfgang, JA Goyal, L Blaszkowsky, LS Zhu, AX Hong, TS AF Keane, F. K. Wo, J. Y. Wolfgang, J. A. Goyal, L. Blaszkowsky, L. S. Zhu, A. X. Hong, T. S. TI Outcomes After Liver Directed Radiation Therapy for Hepatocellular Carcinoma With Tumor Venous Thrombosis SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Keane, F. K.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA USA. [Wo, J. Y.; Wolfgang, J. A.; Hong, T. S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Goyal, L.; Blaszkowsky, L. S.; Zhu, A. X.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2417 BP E163 EP E164 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300417 ER PT J AU Keane, FK Wo, JY Ferrone, CR Lillemoe, KD Clark, J Blaszkowsky, LS Allen, JN Kwak, EL Ryan, DP Warshaw, AL Fernandez-del Castillo, C Hong, TS AF Keane, F. K. Wo, J. Y. Ferrone, C. R. Lillemoe, K. D. Clark, J. Blaszkowsky, L. S. Allen, J. N. Kwak, E. L. Ryan, D. P. Warshaw, A. L. Fernandez-del Castillo, C. Hong, T. S. TI Clinical Predictors and Outcomes of Superior Mesenteric Vein or Portal Vein Thrombosis in the Setting of Neoadjuvant Therapy for Borderline Resectable or Locally Advanced Pancreatic Adenocarcinoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Keane, F. K.] Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA USA. [Wo, J. Y.; Hong, T. S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Ferrone, C. R.; Lillemoe, K. D.; Warshaw, A. L.; Fernandez-del Castillo, C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Clark, J.; Blaszkowsky, L. S.; Allen, J. N.; Kwak, E. L.; Ryan, D. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2356 BP E141 EP E141 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300356 ER PT J AU Kishan, AU Moningi, S Kumar, R Ancukiewicz, M Ahuja, N Gearhart, SL Efron, JE Herman, JM Hong, TS AF Kishan, A. U. Moningi, S. Kumar, R. Ancukiewicz, M. Ahuja, N. Gearhart, S. L. Efron, J. E. Herman, J. M. Hong, T. S. TI Standard Fractionation External Beam Radiation Therapy With and Without Intraoperative Radiation Therapy for Patients With Locally Recurrent Rectal Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Kishan, A. U.] Univ Calif Los Angeles, Los Angeles, CA USA. [Moningi, S.; Herman, J. M.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Kumar, R.] Banner Hlth, Gilbert, AZ USA. [Ancukiewicz, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ahuja, N.; Gearhart, S. L.; Efron, J. E.] Johns Hopkins Univ, Baltimore, MD USA. [Hong, T. S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2368 BP E145 EP E145 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300368 ER PT J AU Kittel, J Funchain, P Chute, D Woody, NM Hammerman, P Koyfman, S Abazeed, M AF Kittel, J. Funchain, P. Chute, D. Woody, N. M. Hammerman, P. Koyfman, S. Abazeed, M. TI Comprehensive Functional Genomic Profiling of HPV Unassociated Head and Neck Squamous Cell Cancer Identifies Neomorphic Mutations That Confer Resistance to Therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Kittel, J.; Funchain, P.; Chute, D.; Woody, N. M.; Koyfman, S.; Abazeed, M.] Cleveland Clin, Cleveland, OH 44106 USA. [Hammerman, P.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 3350 BP E538 EP E538 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301416 ER PT J AU Kovtun, K Penzkofer, T Agrawal, N Kapur, T Andriy, F Cormack, R D'Amico, AV Tempany, CM Nguyen, PL AF Kovtun, K. Penzkofer, T. Agrawal, N. Kapur, T. Andriy, F. Cormack, R. D'Amico, A. V. Tempany, C. M. Nguyen, P. L. TI Location of Local Recurrence After MRI-Guided Partial Prostate Brachytherapy Targeting Only the Peripheral Zone: Implications for Focal Therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Kovtun, K.; Penzkofer, T.; Agrawal, N.; Kapur, T.; Andriy, F.; Cormack, R.; D'Amico, A. V.; Tempany, C. M.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Kovtun, K.] Harvard Radiat Oncol Program, Boston, MA USA. [Penzkofer, T.; Agrawal, N.; Kapur, T.; Andriy, F.; Cormack, R.; D'Amico, A. V.; Tempany, C. M.; Nguyen, P. L.] Harvard Univ, Sch Med, Boston, MA USA. [Nguyen, P. L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nguyen, P. L.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2493 BP E195 EP E195 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300493 ER PT J AU Lin, CC Bruinooge, S Kirkwood, K Hershman, DL Jemal, A Yu, JB Guadagnolo, BA Hopkins, S Goldstein, M Bajorin, D Giordano, S Kosty, M Arnone, A Hanley, A Stevens, S Olsen, CC AF Lin, C. C. Bruinooge, S. Kirkwood, K. Hershman, D. L. Jemal, A. Yu, J. B. Guadagnolo, B. A. Hopkins, S. Goldstein, M. Bajorin, D. Giordano, S. Kosty, M. Arnone, A. Hanley, A. Stevens, S. Olsen, C. C. TI Association Between Geographic Access and Receipt of Radiation Therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Lin, C. C.; Jemal, A.] Amer Canc Soc, Atlanta, GA 30329 USA. [Bruinooge, S.; Kirkwood, K.; Hanley, A.] Amer Soc Clin Oncol, Alexandria, VA USA. [Hershman, D. L.] Columbia Univ, New York, NY USA. [Yu, J. B.] Yale Univ, Sch Med, New Haven, CT USA. [Guadagnolo, B. A.; Giordano, S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Hopkins, S.] William R Bliss Canc Ctr, Des Moines, IA USA. [Goldstein, M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Bajorin, D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Kosty, M.] Scripps Clin, La Jolla, CA 92037 USA. [Arnone, A.; Stevens, S.] Amer Soc Radiat Oncol, Fairfax, VA USA. [Olsen, C. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2915 BP E367 EP E367 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300910 ER PT J AU Ling, DC Chapman, BV Kim, J Choby, G Kabolizadeh, P Clump, DA Ferris, RL Kim, S Beriwal, S Heron, DE Duvvuri, U AF Ling, D. C. Chapman, B. V. Kim, J. Choby, G. Kabolizadeh, P. Clump, D. A., II Ferris, R. L. Kim, S. Beriwal, S. Heron, D. E. Duvvuri, U. TI Oncologic Outcomes and Patient-Reported Quality of Life in Patients With Oropharyngeal Squamous Cell Carcinoma Treated With Primary Transoral Robotic Surgery Versus Definitive Chemoradiation SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Ling, D. C.; Chapman, B. V.; Clump, D. A., II; Beriwal, S.; Heron, D. E.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Kim, J.; Choby, G.; Ferris, R. L.; Kim, S.; Duvvuri, U.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Kabolizadeh, P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2813 BP E327 EP E328 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300809 ER PT J AU Liu, Y Alexander, BM Chen, YH Horvath, MC Aizer, AA Claus, EB Dunn, IF Golby, AJ Johnson, MD Friesen, S Mannarino, E Wagar, M Hacker, FL Arvold, ND AF Liu, Y. Alexander, B. M. Chen, Y. H. Horvath, M. C. Aizer, A. A. Claus, E. B. Dunn, I. F. Golby, A. J. Johnson, M. D. Friesen, S. Mannarino, E. Wagar, M. Hacker, F. L. Arvold, N. D. TI Need for Salvage Whole-Brain Radiation Therapy or Stereotactic Radiosurgery in Patients With 1-4 Brain Metastases Receiving Upfront Stereotactic Radiosurgery SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Liu, Y.; Alexander, B. M.; Horvath, M. C.] Dana Farber Canc Inst, Brigham & Womens Canc Ctr, Boston, MA 02115 USA. [Chen, Y. H.; Claus, E. B.; Golby, A. J.; Johnson, M. D.; Friesen, S.; Mannarino, E.; Wagar, M.; Hacker, F. L.] Brigham & Womens Canc Ctr, Dana Farber, Boston, MA USA. [Aizer, A. A.; Dunn, I. F.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Aizer, A. A.; Dunn, I. F.] Brigham & Womens Canc Ctr, Boston, MA USA. [Arvold, N. D.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2144 BP E58 EP E58 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300145 ER PT J AU Logie, N Jimenez, RB Pulenzas, N Linden, K Ciafone, D Ghosh, S Xu, Y Lefresne, S Wong, E Son, C Shih, HA Wong, WW Dennis, K Chow, E Fairchild, AM AF Logie, N. Jimenez, R. B. Pulenzas, N. Linden, K. Ciafone, D. Ghosh, S. Xu, Y. Lefresne, S. Wong, E. Son, C. Shih, H. A. Wong, W. W. Dennis, K. Chow, E. Fairchild, A. M. TI Outcomes After Whole-Brain Reirradiation for Multiple Brain Metastases: Total Dose Is Associated With Improved Overall Survival SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Logie, N.; Ghosh, S.; Fairchild, A. M.] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. [Jimenez, R. B.; Shih, H. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pulenzas, N.; Wong, E.] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Linden, K.; Xu, Y.; Dennis, K.] Ottawa Canc Ctr, Ottawa, ON, Canada. [Ciafone, D.; Wong, W. W.] Mayo Clin, Phoenix, AZ USA. [Lefresne, S.] BC Canc Agcy, Surrey, BC, Canada. [Son, C.] Univ Chicago, Chicago, IL 60637 USA. [Chow, E.] Univ Toronto, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 3207 BP E483 EP E483 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301274 ER PT J AU Mahal, BA Muralidhar, V Dinh, KT Chen, YW Nezolosky, MD Choueiri, TK Hoffman, KE Hu, JC Sweeney, CJ Yu, JB Trinh, QD Nguyen, PL AF Mahal, B. A. Muralidhar, V. Dinh, K. T. Chen, Y. W. Nezolosky, M. D. Choueiri, T. K. Hoffman, K. E. Hu, J. C. Sweeney, C. J. Yu, J. B. Trinh, Q. D. Nguyen, P. L. TI Gleason 5+3=8 Prostate Cancer: Much More like Gleason 9? SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Mahal, B. A.; Muralidhar, V.; Dinh, K. T.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Y. W.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Nezolosky, M. D.; Nguyen, P. L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Choueiri, T. K.; Sweeney, C. J.; Trinh, Q. D.; Nguyen, P. L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hoffman, K. E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Hu, J. C.] Univ Calif Los Angeles, Los Angeles, CA USA. [Yu, J. B.] Yale Univ, Sch Med, New Haven, CT USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2579 BP E232 EP E233 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300577 ER PT J AU Mak, KS Van Bommel, ACM Stowell, C Abrahm, JL Baker, M Baldotto, C Baldwin, DR Borthwick, D Carbone, DP Chen, AB Haswell, T Koczywas, M Kozower, BD Mehran, RJ Schramel, FM Senan, S Stirling, RG van Meerbeeck, JP Wouters, MWJM Peake, MD AF Mak, K. S. Van Bommel, A. C. M. Stowell, C. Abrahm, J. L. Baker, M. Baldotto, C. Baldwin, D. R. Borthwick, D. Carbone, D. P. Chen, A. B. Haswell, T. Koczywas, M. Kozower, B. D. Mehran, R. J. Schramel, F. M. Senan, S. Stirling, R. G. van Meerbeeck, J. P. Wouters, M. W. J. M. Peake, M. D. TI Defining a Standard Set of Patient Centered Outcomes for Patients With Lung Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Mak, K. S.] Harvard Radiat Oncol Program, Boston, MA USA. [Mak, K. S.; Van Bommel, A. C. M.; Stowell, C.] Int Consortium Hlth Outcomes Measurement, Cambridge, MA USA. [Abrahm, J. L.; Chen, A. B.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Baker, M.] Patient Representat, Manchester, Lancs, England. [Baldotto, C.] Clin Oncol Integradas, Rio De Janeiro, Brazil. [Baldwin, D. R.] Univ Nottingham Hosp, Nottingham NG7 2UH, England. [Borthwick, D.] Edinburgh Canc Res Ctr, Edinburgh, Midlothian, Scotland. [Carbone, D. P.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Haswell, T.] Patient Representat, Glasgow, Lanark, Scotland. [Koczywas, M.] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Kozower, B. D.] Univ Virginia Hlth Syst, Charlottesville, VA USA. [Mehran, R. J.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Schramel, F. M.] St Antonius Hosp, Nieuwegein, Netherlands. [Senan, S.] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands. [Stirling, R. G.] Monash Univ, Alfred Hosp, Melbourne, Vic 3181, Australia. [van Meerbeeck, J. P.] Univ Antwerp Hosp, Edegem, Belgium. [Wouters, M. W. J. M.] Netherlands Canc Inst, Amsterdam, Netherlands. [Wouters, M. W. J. M.] Dutch Inst Clin Auditing, Leiden, Netherlands. [Peake, M. D.] Univ Hosp Leicester, Leicester, Leics, England. [Peake, M. D.] Publ Hlth England, NCIN, London, England. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 3004 BP E403 EP E403 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301073 ER PT J AU Mancias, J Biancur, DE Korideck, H Berbeco, RI Makrigiorgos, G Kimmelman, AC AF Mancias, J. Biancur, D. E. Korideck, H. Berbeco, R. I. Makrigiorgos, G. Kimmelman, A. C. TI Image Guided Radiation Therapy of a Kras-Driven Genetically Engineered Mouse Model of Pancreatic Ductal Adenocarcinoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Mancias, J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Mancias, J.; Biancur, D. E.; Korideck, H.; Kimmelman, A. C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Berbeco, R. I.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Berbeco, R. I.] Harvard Univ, Sch Med, Boston, MA USA. [Makrigiorgos, G.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 3367 BP E545 EP E545 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301432 ER PT J AU Manuel, M Cho, LP Damato, AL Lee, LJ Viswanathan, AN AF Manuel, M. Cho, L. P. Damato, A. L. Lee, L. J. Viswanathan, A. N. TI Are Clinical Outcomes Improved With Image Guided Interstitial Brachytherapy for Vaginal Cancer? SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Manuel, M.; Cho, L. P.; Damato, A. L.; Lee, L. J.; Viswanathan, A. N.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Manuel, M.; Cho, L. P.; Damato, A. L.; Lee, L. J.; Viswanathan, A. N.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2711 BP E285 EP E286 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300707 ER PT J AU Margalit, DN Catalano, PJ Annino, DJ Goguen, LA Haddad, RI Lorch, J Limaye, SA Norris, CM Schoenfeld, JD Sher, DJ Tishler, RB AF Margalit, D. N. Catalano, P. J. Annino, D. J. Goguen, L. A. Haddad, R. I. Lorch, J. Limaye, S. A. Norris, C. M. Schoenfeld, J. D. Sher, D. J. Tishler, R. B. TI Patterns of Failure After Reirradiation (reRT) With Intensity Modulated Radiation Therapy (IMRT): Not Just a Local Issue SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Margalit, D. N.; Annino, D. J.; Goguen, L. A.; Norris, C. M.; Schoenfeld, J. D.; Tishler, R. B.] Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. [Catalano, P. J.; Haddad, R. I.; Lorch, J.; Limaye, S. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sher, D. J.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2844 BP E340 EP E340 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300840 ER PT J AU Mayo, C Moran, JM Xiao, Y Bosch, WR Matuszak, MM Marks, LB Miller, RC Wu, QRJ Yock, TI Popple, R McNutt, TR Brown, N Molineu, A Purdie, TG Yorke, ED Santanam, L Gabriel, P Michalski, JM Moore, J Richardson, S Siochi, RAC Napolitano, M Feng, M Fitzgerald, T Ulin, K Verbakel, WFAR Siddiqui, MSU Martel, MK Archambault, Y Morgas, T Purcy, J Adams, JA Ladra, M Lansing, B Ruo, R Fogliata, A Hurkmans, C AF Mayo, C. Moran, J. M. Xiao, Y. Bosch, W. R. Matuszak, M. M. Marks, L. B. Miller, R. C. Wu, Q. R. J. Yock, T. I. Popple, R. McNutt, T. R. Brown, N. Molineu, A. Purdie, T. G. Yorke, E. D. Santanam, L. Gabriel, P. Michalski, J. M. Moore, J. Richardson, S. Siochi, R. A. C. Napolitano, M. Feng, M. Fitzgerald, T. Ulin, K. Verbakel, W. F. A. R. Siddiqui, M. S. U. Martel, M. K. Archambault, Y. Morgas, T. Purcy, J. Adams, J. A. Ladra, M. Lansing, B. Ruo, R. Fogliata, A. Hurkmans, C. TI AAPM Task Group 263: Tackling Standardization of Nomenclature for Radiation Therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Mayo, C.] Mayo Clin, Rochester, MN USA. [Moran, J. M.; Matuszak, M. M.; Feng, M.] Univ Michigan, Ann Arbor, MI 48109 USA. [Xiao, Y.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Bosch, W. R.; Santanam, L.; Michalski, J. M.] Washington Univ, Sch Med, St Louis, MO USA. [Marks, L. B.] UNC Sch Med, Chapel Hill, NC USA. [Miller, R. C.] Mayo Clin, Jacksonville, FL 32224 USA. [Wu, Q. R. J.] Duke Univ, Med Ctr, Durham, NC USA. [Yock, T. I.; Adams, J. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Popple, R.] Univ Alabama Birmingham, Birmingham, AL USA. [McNutt, T. R.; Moore, J.] Johns Hopkins Univ, Baltimore, MD USA. [Brown, N.] Baptist Med Ctr, Jacksonville, FL USA. [Molineu, A.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Purdie, T. G.] Princess Margaret Hosp, Toronto, ON, Canada. [Yorke, E. D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Gabriel, P.] Univ Penn, Philadelphia, PA 19104 USA. [Richardson, S.] Swedish Canc Inst, Seattle, WA USA. [Siochi, R. A. C.] W Virginia Univ, Morgantown, WV 26506 USA. [Napolitano, M.] Independent, Suwanee, GA USA. [Fitzgerald, T.] Univ Massachusetts, Med Ctr, Worcester, MA USA. [Ulin, K.] Univ Massachusetts, Mem Med Ctr, Worcester, MA 01605 USA. [Verbakel, W. F. A. R.] Vrije Univ Amsterdam Med Ctr, NL-1007 MB Amsterdam, Netherlands. [Siddiqui, M. S. U.] Henry Ford Hlth Syst, Detroit, MI USA. [Martel, M. K.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Archambault, Y.; Morgas, T.] Varian Med Syst, Palo Alto, CA USA. [Purcy, J.] Elekta Med Syst, St Louis, MO USA. [Ladra, M.] Provis Ctr Proton Therapy, Knoxville, TN USA. [Lansing, B.] Elekta, Maryland Hts, MD USA. [Ruo, R.] Montreal Gen Hosp, Montreal, PQ H3G 1A4, Canada. [Fogliata, A.] Ist Clin Humanitas IRCCS Milano, Milan, Italy. [Hurkmans, C.] Catharina Hosp, Eindhoven, Netherlands. NR 0 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2955 BP E383 EP E384 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301024 ER PT J AU Muralidhar, V Tucker-Seeley, RD Nguyen, PL AF Muralidhar, V. Tucker-Seeley, R. D. Nguyen, P. L. TI Recent Financial Hardship and Decreased Survival Following a Cancer Diagnosis SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Muralidhar, V.] Harvard Univ, Sch Med, Boston, MA USA. [Tucker-Seeley, R. D.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Nguyen, P. L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nguyen, P. L.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2883 BP E355 EP E355 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300879 ER PT J AU Muralidhar, V Mahal, BA Ziehr, DR Chen, YW Nezolosky, MD Viswanathan, VB Beard, CJ Devlin, PM Martin, NE Orio, P Nguyen, PL AF Muralidhar, V. Mahal, B. A. Ziehr, D. R. Chen, Y. W. Nezolosky, M. D. Viswanathan, V. B. Beard, C. J. Devlin, P. M. Martin, N. E. F Orio, P., III Nguyen, P. L. TI Shifting Brachytherapy Monotherapy Case Mix Toward Intermediate-Risk Prostate Cancer: Implications for Future Directions of Research SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Muralidhar, V.; Mahal, B. A.; Ziehr, D. R.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Y. W.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Nezolosky, M. D.; Viswanathan, V. B.; Devlin, P. M.; F Orio, P., III; Nguyen, P. L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Beard, C. J.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Martin, N. E.; Nguyen, P. L.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2882 BP E354 EP E355 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300878 ER PT J AU Muralidhar, V Mahal, BA Nguyen, PL AF Muralidhar, V. Mahal, B. A. Nguyen, P. L. TI Conditional Cancer-Specific Survival in Prostate Cancer Patients With Very-High-Risk Features: Implications for Long-Term Prognosis SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Muralidhar, V.; Mahal, B. A.] Harvard Univ, Sch Med, Boston, MA USA. [Nguyen, P. L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nguyen, P. L.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2514 BP E204 EP E204 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300514 ER PT J AU Muralidhar, V Ziehr, DR Mahal, BA Chen, YW Nezolosky, MD Viswanathan, VB Choueiri, TK Sweeney, CJ Trinh, QD Nguyen, PL AF Muralidhar, V. Ziehr, D. R. Mahal, B. A. Chen, Y. W. Nezolosky, M. D. Viswanathan, V. B. Choueiri, T. K. Sweeney, C. J. Trinh, Q. D. Nguyen, P. L. TI Older Age and Increasing Gleason Score: Implications for Prostate Cancer Screening SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Muralidhar, V.; Ziehr, D. R.; Mahal, B. A.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Y. W.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Nezolosky, M. D.; Viswanathan, V. B.; Nguyen, P. L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Choueiri, T. K.; Sweeney, C. J.; Trinh, Q. D.; Nguyen, P. L.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2502 BP E199 EP E199 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300502 ER PT J AU Muralidhar, V Dinh, KT Mahal, BA Ziehr, DR Chen, YW Viswanathan, VB Nezolosky, MD Choueiri, TK Hoffman, KE Hu, JC Sweeney, CJ Trinh, QD Nguyen, PL AF Muralidhar, V. Dinh, K. T. Mahal, B. A. Ziehr, D. R. Chen, Y. W. Viswanathan, V. B. Nezolosky, M. D. Choueiri, T. K. Hoffman, K. E. Hu, J. C. Sweeney, C. J. Trinh, Q. D. Nguyen, P. L. TI Differential Postprostatectomy Cancer-Specific Mortality of Occult T3 Versus Clinical T3 Prostate Cancer: Implications for Radiation Managed Patients Upstaged on Prostate MRI SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Muralidhar, V.; Dinh, K. T.; Mahal, B. A.; Ziehr, D. R.] Harvard Univ, Sch Med, Boston, MA USA. [Chen, Y. W.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Viswanathan, V. B.; Nezolosky, M. D.; Nguyen, P. L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Choueiri, T. K.; Sweeney, C. J.; Trinh, Q. D.; Nguyen, P. L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hoffman, K. E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Hu, J. C.] Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2501 BP E199 EP E199 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300501 ER PT J AU Nezolosky, MD Dinh, KT Muralidhar, V Nguyen, PL AF Nezolosky, M. D. Dinh, K. T. Muralidhar, V. Nguyen, P. L. TI Significant Increase in Prostatectomy for Clinical T3 Prostate Cancer From 1995 to 2011 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Nezolosky, M. D.; Nguyen, P. L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Dinh, K. T.; Muralidhar, V.] Harvard Univ, Sch Med, Boston, MA USA. [Nguyen, P. L.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2621 BP E250 EP E250 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300619 ER PT J AU Niu, NN Catalano, PJ Enzinger, PC Bueno, R King, BL Martin, NE Kimmelman, AC Hong, TS Wo, JY Mamon, HJ AF Niu, N. N. Catalano, P. J. Enzinger, P. C. Bueno, R. King, B. L. Martin, N. E. Kimmelman, A. C. Hong, T. S. Wo, J. Y. Mamon, H. J. TI A Retrospective Comparison of Neoadjuvant Chemoradiation Therapy Regimens for Locally Advanced Esophageal Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Niu, N. N.] Harvard Radiat Oncol Program, Boston, MA USA. [Catalano, P. J.; Enzinger, P. C.; Bueno, R.; King, B. L.; Martin, N. E.; Kimmelman, A. C.; Mamon, H. J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bueno, R.; King, B. L.; Martin, N. E.; Kimmelman, A. C.; Mamon, H. J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hong, T. S.; Wo, J. Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2352 BP E139 EP E139 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300352 ER PT J AU Okwan-Duodu, D Patel, K Zhong, J Prabhu, RS Eaton, BR Olson, J Shu, HKG Curran, WJ Crocker, IR AF Okwan-Duodu, D. Patel, K. Zhong, J. Prabhu, R. S. Eaton, B. R. Olson, J. Shu, H. K. G. Curran, W. J., Jr. Crocker, I. R. TI Impact of Angiotensin Blockade on Symptomatic Radiation Necrosis Following Stereotactic Radiosurgery SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Okwan-Duodu, D.; Patel, K.; Olson, J.; Curran, W. J., Jr.; Crocker, I. R.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Zhong, J.] Emory Univ, Atlanta, GA 30322 USA. [Zhong, J.] Winship Canc Inst, Atlanta, GA USA. [Prabhu, R. S.] Levine Canc Inst, Southeast Radiat Oncol Grp, Charlotte, NC USA. [Eaton, B. R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2896 BP E360 EP E360 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300891 ER PT J AU Patel, SA Tan, T Chin, JY Lu, HM Depauw, N Kooy, HM Taghian, AG Scherrer-Crosbie, M Passeri, J MacDonald, S AF Patel, S. A. Tan, T. Chin, J. Y. Lu, H. M. Depauw, N. Kooy, H. M. Taghian, A. G. Scherrer-Crosbie, M. Passeri, J. MacDonald, S. TI Assessment of Cardiac Function Following Proton Radiation in a Cohort of Postmastectomy Patients with Locally Advanced Breast Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Patel, S. A.; Chin, J. Y.] Harvard Radiat Oncol Program, Boston, MA USA. [Tan, T.; Scherrer-Crosbie, M.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Lu, H. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Depauw, N.; Kooy, H. M.; Taghian, A. G.; MacDonald, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Passeri, J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2127 BP E52 EP E52 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300129 ER PT J AU Phillips, J Mak, KS Barysauskas, C Vanbenthuysen, L Mannarino, E DeLaney, TF Baldini, EH AF Phillips, J. Mak, K. S. Barysauskas, C. Vanbenthuysen, L. Mannarino, E. DeLaney, T. F. Baldini, E. H. TI Updated Analysis of Bowel Bag (BB) Dose Volume Parameters and Acute Gastrointestinal (GI) Toxicity During Preoperative (Preop) Radiation Therapy (RT) for Retroperitoneal Sarcoma (RPS) SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Phillips, J.; Mak, K. S.] Harvard Univ, Radiat Oncol Program, Boston, MA 02115 USA. [Barysauskas, C.] DFCI Biostat & Computat Biol, Boston, MA USA. [Vanbenthuysen, L.; DeLaney, T. F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mannarino, E.] Brigham & Womens Hosp, Fall River, MA USA. [Baldini, E. H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Baldini, E. H.] BWH, Boston, MA USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 3590 BP E634 EP E634 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301652 ER PT J AU Phillips, J Schoenfeld, JD Shui, I Batista, J Margalit, DN Nguyen, PL Mucci, L AF Phillips, J. Schoenfeld, J. D. Shui, I. Batista, J. Margalit, D. N. Nguyen, P. L. Mucci, L. TI Association Between Single Nucleotide Polymorphisms (SNPs) in Inflammation Related Genes and Quality of Life (QOL) after Radiation Therapy (RT) for Prostate Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Phillips, J.] Harvard Radiat Oncol Program, Boston, MA USA. [Schoenfeld, J. D.; Margalit, D. N.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Shui, I.; Batista, J.; Mucci, L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Nguyen, P. L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nguyen, P. L.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 3301 BP E520 EP E520 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301367 ER PT J AU Phillips, J Gueorguiev, G Grassberger, C Choi, NC Paganetti, H Sharp, GC AF Phillips, J. Gueorguiev, G. Grassberger, C. Choi, N. C. Paganetti, H. Sharp, G. C. TI Effects of Excess Breathing Motion on Proton Dose Coverage SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Phillips, J.; Gueorguiev, G.; Grassberger, C.; Choi, N. C.; Sharp, G. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Paganetti, H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 3084 BP E435 EP E435 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301152 ER PT J AU Przybysz, D Hill, EK Dizon, DS AF Przybysz, D. Hill, E. K. Dizon, D. S. TI Sexual Dysfunction After Cancer: Findings From the Program in Women's Oncology Center for Sexuality, Intimacy, and Fertility SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Przybysz, D.; Dizon, D. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Przybysz, D.] Harvard Univ, Sch Med, Boston, MA USA. [Hill, E. K.] Brown Univ, Warren Alpert Med Sch, Dudley, RI USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 3216 BP E487 EP E487 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301283 ER PT J AU Raldow, A Zhang, D Chen, MH Braccioforte, MH Moran, BJ D'Amico, AV AF Raldow, A. Zhang, D. Chen, M. H. Braccioforte, M. H. Moran, B. J. D'Amico, A. V. TI Risk Group and Death From Prostate Cancer Among Men Undergoing Brachytherapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Raldow, A.] Harvard Radiat Oncol Program, Boston, MA USA. [Zhang, D.; Chen, M. H.] Univ Connecticut, Storrs, CT USA. [Braccioforte, M. H.; Moran, B. J.] Prostate Canc Fdn Chicago, Westmont, IL USA. [D'Amico, A. V.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2532 BP E212 EP E212 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300532 ER PT J AU Rose, B Jee, KW Niemierko, A Murphy, JE Blaszkowsky, LS Allen, JN Lee, LK Wang, Y Drapek, LC Hong, TS Wo, JY AF Rose, B. Jee, K. W. Niemierko, A. Murphy, J. E. Blaszkowsky, L. S. Allen, J. N. Lee, L. K. Wang, Y. Drapek, L. C. Hong, T. S. Wo, J. Y. TI Irradiation of FDG-PET Defined-Active Bone Marrow Subregions and Acute Hematologic Toxicity in Anal Cancer Patients Undergoing Chemoradiation SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Rose, B.] Harvard Radiat Oncol Program, Boston, MA USA. [Jee, K. W.; Niemierko, A.; Murphy, J. E.; Blaszkowsky, L. S.; Allen, J. N.; Lee, L. K.; Wang, Y.; Drapek, L. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hong, T. S.; Wo, J. Y.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2441 BP E173 EP E173 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300441 ER PT J AU Royce, TJ Kosak, TK Cerrato, CM Greer, L McKay, A Broudo, M Napolitano, BN Busse, PM Hong, TS Wolfgang, JA AF Royce, T. J. Kosak, T. K. Cerrato, C. M. Greer, L. McKay, A. Broudo, M. Napolitano, B. N. Busse, P. M. Hong, T. S. Wolfgang, J. A. TI Eliminating Treatment Planning Delays With a Web-Based Tracking and Communication System SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Royce, T. J.; Cerrato, C. M.; Greer, L.; McKay, A.; Broudo, M.; Napolitano, B. N.; Busse, P. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kosak, T. K.; Hong, T. S.; Wolfgang, J. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 3234 BP E494 EP E494 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301301 ER PT J AU Russo, AL Turcotte, JC Rochet, N Russell, AH AF Russo, A. L. Turcotte, J. C. Rochet, N. Russell, A. H. TI Whole-Abdominal Irradiation Using Intensity Modulated Radiation Therapy for Select Patients With Regionally Advanced or Recurrent Uterine Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Russo, A. L.; Turcotte, J. C.; Russell, A. H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rochet, N.] Heidelberg Univ, Heidelberg, Germany. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2708 BP E284 EP E285 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300704 ER PT J AU Tanguturi, S Niemierko, A Wo, JY Nguyen, KN Prichard, H Wolfgang, JA Hong, TS AF Tanguturi, S. Niemierko, A. Wo, J. Y. Nguyen, K. N. Prichard, H. Wolfgang, J. A. Hong, T. S. TI Gallbladder Toxicity and High Dose Ablative Intent Radiation for Liver Tumors: Should We Constrain the Dose? SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Tanguturi, S.] Harvard Radiat Oncol Program, Boston, MA USA. [Niemierko, A.; Nguyen, K. N.; Prichard, H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wo, J. Y.; Wolfgang, J. A.; Hong, T. S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2318 BP E125 EP E125 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300319 ER PT J AU Tanguturi, S Kambadakone, A Niemierko, A Nguyen, KN Wo, JY Blaszkowsky, LS Goyal, L Wolfgang, JA Zhu, AX Hong, TS AF Tanguturi, S. Kambadakone, A. Niemierko, A. Nguyen, K. N. Wo, J. Y. Blaszkowsky, L. S. Goyal, L. Wolfgang, J. A. Zhu, A. X. Hong, T. S. TI Early Response Assessment After Hypofractionated Proton Radiation Therapy for Primary Liver Tumors SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Tanguturi, S.] Harvard Radiat Oncol Program, Boston, MA USA. [Kambadakone, A.; Niemierko, A.; Nguyen, K. N.; Blaszkowsky, L. S.; Goyal, L.; Zhu, A. X.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wo, J. Y.; Wolfgang, J. A.; Hong, T. S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2317 BP E125 EP E125 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300318 ER PT J AU Tanguturi, S Lyatskaya, Y Chen, YH Catalano, PJ Truong, LT Yeh, M Yeo, WP Orlina, LA Wong, JS Punglia, RS Bellon, JR AF Tanguturi, S. Lyatskaya, Y. Chen, Y. H. Catalano, P. J. Truong, L. T. Yeh, M. Yeo, W. P. Orlina, L. A. Wong, J. S. Punglia, R. S. Bellon, J. R. TI Prospective Assessment of Deep Inspiration Breath Hold Using 3-Dimensional Surface Tracking for Irradiation of Left-Sided Breast Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Tanguturi, S.] Harvard Radiat Oncol Program, Boston, MA USA. [Lyatskaya, Y.; Truong, L. T.; Yeo, W. P.; Orlina, L. A.; Wong, J. S.; Punglia, R. S.; Bellon, J. R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Chen, Y. H.; Catalano, P. J.; Yeh, M.; Wong, J. S.; Punglia, R. S.; Bellon, J. R.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2009 BP E4 EP E4 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300011 ER PT J AU Wang, EH Corso, C Rutter, CE Park, HSM Chen, AB Kim, AW Wilson, LD Decker, RH Yu, JB AF Wang, E. H. Corso, C. Rutter, C. E. Park, H. S. M. Chen, A. B. Kim, A. W. Wilson, L. D. Decker, R. H. Yu, J. B. TI Postoperative Radiation Therapy Is Associated With Improved Overall Survival in Incompletely Resected Stage II and III Non- Small Cell Lung Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Wang, E. H.; Rutter, C. E.; Park, H. S. M.; Kim, A. W.; Wilson, L. D.; Decker, R. H.; Yu, J. B.] Yale Univ, Sch Med, New Haven, CT USA. [Corso, C.] Yale Univ, New Haven, CT USA. [Chen, A. B.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2968 BP E388 EP E389 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301037 ER PT J AU Wang, EH Corso, C Park, HSM Chen, AB Kim, AW Wilson, LD Decker, RH Yu, JB AF Wang, E. H. Corso, C. Park, H. S. M. Chen, A. B. Kim, A. W. Wilson, L. D. Decker, R. H. Yu, J. B. TI Association Between Radiation Dose and Outcomes With Postoperative Radiation Therapy for N0-N1 Non-Small Cell Lung Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Wang, E. H.; Park, H. S. M.; Kim, A. W.; Wilson, L. D.; Decker, R. H.; Yu, J. B.] Yale Univ, Sch Med, New Haven, CT USA. [Corso, C.] Yale Univ, New Haven, CT USA. [Chen, A. B.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2966 BP E387 EP E388 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301035 ER PT J AU Warren, L Kim, M Martin, NE Shih, HA AF Warren, L. Kim, M. Martin, N. E. Shih, H. A. TI An Analysis of After Hours Patient Phone Calls in Two Academic Radiation Oncology Departments: An Opportunity for Safety and Quality Improvement SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Warren, L.; Kim, M.] Harvard Radiat Oncol Program, Boston, MA USA. [Martin, N. E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Shih, H. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 3243 BP E497 EP E498 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301310 ER PT J AU Winkfield, KM Gallotto, S Niemierko, A Adams, JA Tarbell, NJ Chen, YL AF Winkfield, K. M. Gallotto, S. Niemierko, A. Adams, J. A. Tarbell, N. J. Chen, Y. L. TI Proton Therapy for Mediastinal Lymphomas: An 8-year Single-institution Report SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Winkfield, K. M.; Gallotto, S.; Niemierko, A.; Adams, J. A.; Chen, Y. L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tarbell, N. J.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 3152 BP E461 EP E461 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301219 ER PT J AU Wong, JS Chen, YH Truong, T Bellon, JR Punglia, RS Moreau, JM Chun, YS Hergrueter, CA AF Wong, J. S. Chen, Y. H. Truong, T. Bellon, J. R. Punglia, R. S. Moreau, J. M. Chun, Y. S. Hergrueter, C. A. TI Effects of Postmastectomy Radiation Therapy on Immediate Tissue Expander and Acellular Dermal Matrix Reconstruction SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Wong, J. S.; Chen, Y. H.; Bellon, J. R.; Punglia, R. S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wong, J. S.; Truong, T.; Bellon, J. R.; Punglia, R. S.; Moreau, J. M.; Chun, Y. S.; Hergrueter, C. A.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 2026 BP E11 EP E11 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215300028 ER PT J AU Zairis, S Margalit, DN Powlis, WD Tishler, RB Schoenfeld, JD AF Zairis, S. Margalit, D. N. Powlis, W. D. Tishler, R. B. Schoenfeld, J. D. TI Prospective Analysis of Radiation Oncology Peer Review for Head and Neck Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Zairis, S.] Columbia Univ, New York, NY USA. [Margalit, D. N.; Tishler, R. B.; Schoenfeld, J. D.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Powlis, W. D.] Brigham & Womens Canc Ctr, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 3232 BP E493 EP E493 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301299 ER PT J AU Abazeed, M Adams, D Hammerman, P Tamayo, P Yard, B Meyerson, M Schreiber, S AF Abazeed, M. Adams, D. Hammerman, P. Tamayo, P. Yard, B. Meyerson, M. Schreiber, S. TI Systematic Investigation of Genetic Vulnerabilities Across Cancer Cell Lines Reveals Lineage Specific Radiotherapeutic Determinants SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Abazeed, M.; Yard, B.] Cleveland Clin, Cleveland, OH 44106 USA. [Adams, D.; Tamayo, P.] Broad Inst, Cambridge, MA USA. [Hammerman, P.; Meyerson, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schreiber, S.] Harvard Univ, Cambridge, MA 02138 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 326 BP S143 EP S144 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215302022 ER PT J AU Agarwal, I Makar, M Noveroske, S Krishnan, MS Taylor, A Gorman, D Balboni, TA AF Agarwal, I. Makar, M. Noveroske, S. Krishnan, M. S. Taylor, A. Gorman, D. Balboni, T. A. TI Impact of a Dedicated Palliative Radiation Oncology Service on the Use of Single-Fraction and Hypofractionated Radiation Therapy Among Patients With Bone Metastases SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Agarwal, I.; Balboni, T. A.] Harvard Univ, Sch Med, Boston, MA USA. [Makar, M.; Krishnan, M. S.; Taylor, A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Noveroske, S.; Gorman, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 141 BP S63 EP S64 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301812 ER PT J AU Agrawal, S Pisansky, TM Hamstra, DA Liauw, S Koontz, BF Efstathiou, JA Michalski, JM Feng, FY Abramowitz, MC Pollack, A Anscher, MS Moghanaki, D Den, RB Stephans, KL Kattan, M Stephenson, AJ Tendulkar, RD AF Agrawal, S. Pisansky, T. M. Hamstra, D. A. Liauw, S. Koontz, B. F. Efstathiou, J. A. Michalski, J. M. Feng, F. Y. Abramowitz, M. C. Pollack, A. Anscher, M. S. Moghanaki, D. Den, R. B. Stephans, K. L. Kattan, M. Stephenson, A. J. Tendulkar, R. D. TI Dose Response for Salvage Radiation Therapy After Radical Prostatectomy in Margin-Positive Prostate Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Agrawal, S.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Pisansky, T. M.] Mayo Clin, Rochester, MN USA. [Hamstra, D. A.; Feng, F. Y.] Univ Michigan, Ann Arbor, MI 48109 USA. [Liauw, S.] Univ Chicago, Chicago, IL 60637 USA. [Koontz, B. F.] Duke Univ, Med Ctr, Durham, NC USA. [Efstathiou, J. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Michalski, J. M.] Washington Univ, Sch Med, St Louis, MO USA. [Abramowitz, M. C.; Pollack, A.] Univ Miami, Miami, FL USA. [Anscher, M. S.; Moghanaki, D.] Virginia Commonwealth Univ, Med Ctr, Richmond, VA USA. [Den, R. B.; Stephans, K. L.] Thomas Jefferson Univ, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA. [Kattan, M.; Stephenson, A. J.; Tendulkar, R. D.] Cleveland Clin, Cleveland, OH 44106 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 303 BP S132 EP S133 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301974 ER PT J AU Aizer, AA Abedalthagafi, M Bi, L Horvath, MC Ligon, AH Arvold, ND Dunn, IF Santagata, S Alexander, B AF Aizer, A. A. Abedalthagafi, M. Bi, L. Horvath, M. C. Ligon, A. H. Arvold, N. D. Dunn, I. F. Santagata, S. Alexander, B. TI A Prognostic Molecular Scoring System to Guide the Adjuvant Management of Patients With Gross Totally Resected Atypical Meningioma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Aizer, A. A.; Arvold, N. D.; Dunn, I. F.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Aizer, A. A.; Arvold, N. D.; Dunn, I. F.] Brigham & Womens Canc Ctr, Boston, MA USA. [Abedalthagafi, M.; Bi, L.; Ligon, A. H.; Santagata, S.; Alexander, B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Horvath, M. C.] Brigham & Womens Canc Ctr, Dana Farber Canc Inst, Boston, MA USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 1028 BP S167 EP S167 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215302081 ER PT J AU Alcorn, SR Bojechko, C Rubo, RA Chen, MJ Dieckmann, K Ermoian, RP Ford, EC MacDonald, S McNutt, TR Nechesnyuk, A Nilsson, K Sjoestrand, HC Smith, KS Tryggestad, EJ Villar, RC Winey, B Terezakis, SA AF Alcorn, S. R. Bojechko, C. Rubo, R. A. Chen, M. J. Dieckmann, K. Ermoian, R. P. Ford, E. C. MacDonald, S. McNutt, T. R. Nechesnyuk, A. Nilsson, K. Sjoestrand, H. C. Smith, K. S. Tryggestad, E. J. Villar, R. C. Winey, B. Terezakis, S. A. TI Predictors of Setup Accuracy in Image Guided CNS Radiation Therapy: Final Analysis From a Prospective Low-Dose Cone Beam CT Protocol From a Multinational Pediatrics Consortium SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Alcorn, S. R.; McNutt, T. R.; Terezakis, S. A.] Johns Hopkins Univ, Baltimore, MD USA. [Bojechko, C.; Ford, E. C.] Univ Washington, Seattle, WA 98195 USA. [Rubo, R. A.; Villar, R. C.] Ctr Infantil Boldrini, Campinas, SP, Brazil. [Chen, M. J.] AC Camargo Canc Ctr, Sao Paulo, Brazil. [Dieckmann, K.] Univ Klin Strahlentherapie & Strahlenbiol, Vienna, Austria. [Ermoian, R. P.] Univ Washington, Med Ctr, Seattle, WA 98195 USA. [MacDonald, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Nechesnyuk, A.] Fed Sci Clin Ctr Childrens Hematol & Immunol, Moscow, Russia. [Nilsson, K.; Sjoestrand, H. C.] Akad Sjukhuset, Uppsala, Sweden. [Smith, K. S.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Tryggestad, E. J.] Mayo Clin, Eau Claire, WI USA. [Winey, B.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 1096 BP S196 EP S197 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215302149 ER PT J AU Braunstein, LZ Liu, Y Horvath, MC Alexander, BM Arvold, ND AF Braunstein, L. Z. Liu, Y. Horvath, M. C. Alexander, B. M. Arvold, N. D. TI Incidence of Late Brain Metastases After Upfront Stereotactic Radiosurgery: Implications for Duration of MRI Surveillance Among Survivors SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Braunstein, L. Z.] Harvard Radiat Oncol Program, Boston, MA USA. [Liu, Y.; Horvath, M. C.; Alexander, B. M.] Brigham & Womens Canc Ctr, Dana Farber Canc Inst, Boston, MA USA. [Arvold, N. D.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 1052 BP S178 EP S178 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215302105 ER PT J AU Buscariollo, D Clayman, RH Galland, S Feldman, AS Dahl, DM McGovern, FJ Olumi, A Eidelman, A Niemierko, A Shipley, WU Zietman, AL Efstathiou, JA AF Buscariollo, D. Clayman, R. H. Galland, S. Feldman, A. S. Dahl, D. M. McGovern, F. J. Olumi, A. Eidelman, A. Niemierko, A. Shipley, W. U. Zietman, A. L. Efstathiou, J. A. TI Long-term Results of Early Salvage Versus Adjuvant Postprostatectomy Radiation: A Large Institutional Experience SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Buscariollo, D.; Clayman, R. H.; Feldman, A. S.; Dahl, D. M.; McGovern, F. J.; Olumi, A.; Eidelman, A.; Niemierko, A.; Shipley, W. U.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Galland, S.] Bordeaux Hosp Univ, Bordeaux, Aquitaine, France. [Zietman, A. L.; Efstathiou, J. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 302 BP S132 EP S132 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301973 ER PT J AU Chen, YL Yoon, SS Choy, E Hornicek, FJ Mullen, JT DeLaney, TF AF Chen, Y. L. Yoon, S. S. Choy, E. Hornicek, F. J. Mullen, J. T. DeLaney, T. F. TI Long-term Follow-up of Preoperative Bevacizumab and Radiation in Soft Tissue Sarcomas SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Chen, Y. L.; Mullen, J. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yoon, S. S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Choy, E.; Hornicek, F. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [DeLaney, T. F.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 61 BP S28 EP S28 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301732 ER PT J AU Chie, EK Hearn, JWD Adams, D Tamayo, P Hammerman, P Abazeed, M AF Chie, E. K. Hearn, J. W. D. Adams, D. Tamayo, P. Hammerman, P. Abazeed, M. TI Comprehensive Genomic Profiling Identifies BRAF Mutations as Novel Radiotherapeutic Targets in Lung Adenocarcinoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Chie, E. K.; Hearn, J. W. D.; Abazeed, M.] Cleveland Clin, Cleveland, OH 44106 USA. [Adams, D.; Tamayo, P.] Broad Inst, Cambridge, MA USA. [Hammerman, P.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 332 BP S146 EP S146 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215302028 ER PT J AU Christodouleas, JP Baumann, BC Bosch, WR Bahl, A Birtle, A Breau, R Challapalli, A Chang, AJ Choudhury, A Daneshmand, S Feldman, AS Guzzo, T Hilman, S Jani, A Malkowicz, B Master, VA Mitra, A Porten, S Efstathiou, JA Eapen, L AF Christodouleas, J. P. Baumann, B. C. Bosch, W. R. Bahl, A. Birtle, A. Breau, R. Challapalli, A. Chang, A. J. Choudhury, A. Daneshmand, S. Feldman, A. S. Guzzo, T. Hilman, S. Jani, A. Malkowicz, B. Master, V. A. Mitra, A. Porten, S. Efstathiou, J. A. Eapen, L. TI Development and Validation of Contouring Guidelines for Postcystectomy Adjuvant Radiation of Bladder Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Christodouleas, J. P.; Baumann, B. C.; Guzzo, T.; Malkowicz, B.] Univ Penn, Philadelphia, PA 19104 USA. [Bosch, W. R.] Washington Univ, Sch Med, St Louis, MO USA. [Bahl, A.] UHBristol NHS Fdn Trust, Bristol, Avon, England. [Birtle, A.] Royal Preston Hosp, Preston, Lancs, England. [Breau, R.; Eapen, L.] Ottawa Hosp, Ottawa, ON, Canada. [Challapalli, A.] Univ London Imperial Coll Sci Technol & Med, London, England. [Chang, A. J.; Porten, S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Choudhury, A.] Christie NHS Fdn Trust, Manchester, Lancs, England. [Daneshmand, S.] Univ So Calif, Los Angeles, CA USA. [Feldman, A. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hilman, S.] Weston Gen Hosp, Weston Super Mare, Somerset, England. [Jani, A.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Master, V. A.] Emory Univ, Atlanta, GA 30322 USA. [Mitra, A.] UCL, London, England. [Efstathiou, J. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 53 BP S24 EP S25 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301724 ER PT J AU Eaton, BR Kuhlthau, K Goldberg, S Srichankij, S Grieco, J Pulsifer, M MacDonald, S Tarbell, NJ Yock, TI AF Eaton, B. R. Kuhlthau, K. Goldberg, S. Srichankij, S. Grieco, J. Pulsifer, M. MacDonald, S. Tarbell, N. J. Yock, T. I. TI Prospective Assessment of Health Related Quality of Life and School Functioning Among Children Who Received Proton Radiation Therapy for a Brain Tumor at <= 3 Years Old SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Eaton, B. R.; Kuhlthau, K.; Goldberg, S.; Srichankij, S.; Grieco, J.; Pulsifer, M.; MacDonald, S.; Yock, T. I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tarbell, N. J.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 73 BP S33 EP S33 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301744 ER PT J AU Giacalone, NJ Clayman, RH Efstathiou, JA Niemierko, A Heney, NM Michaelson, MD McGovern, FJ Kaufman, DS Zietman, AL Shipley, WU AF Giacalone, N. J. Clayman, R. H. Efstathiou, J. A. Niemierko, A. Heney, N. M. Michaelson, M. D. McGovern, F. J. Kaufman, D. S. Zietman, A. L. Shipley, W. U. TI Long-term Outcomes After Bladder-Preserving Combined Modality Therapy for Patients With Muscle-Invasive Bladder Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Giacalone, N. J.] Harvard Radiat Oncol Program, Boston, MA USA. [Clayman, R. H.; Niemierko, A.; Heney, N. M.; Michaelson, M. D.; McGovern, F. J.; Kaufman, D. S.; Shipley, W. U.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Efstathiou, J. A.; Zietman, A. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 49 BP S22 EP S23 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301720 ER PT J AU Giantsoudi, D Kim, V Adams, JA MacDonald, S Paganetti, H AF Giantsoudi, D. Kim, V. Adams, J. A. MacDonald, S. Paganetti, H. TI LET Versus Dose-Sparing of the Brainstem in Proton Radiation Therapy: Treatment Technique Comparison for Posterior Fossa Tumors Based on Variable RBE SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Giantsoudi, D.; Paganetti, H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Kim, V.; Adams, J. A.; MacDonald, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 1097 BP S197 EP S197 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215302150 ER PT J AU Grieco, J Eaton, BR Pulsifer, B Evans, C Kuhlthau, K MacDonald, S Tarbell, NJ Yock, TI Pulsifer, M AF Grieco, J. Eaton, B. R. Pulsifer, B. Evans, C. Kuhlthau, K. MacDonald, S. Tarbell, N. J. Yock, T. I. Pulsifer, M. TI Developmental and Behavioral Functioning in Very Young Children Following Proton Radiation Therapy for Brain Tumors SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Grieco, J.; Eaton, B. R.; Pulsifer, B.; Evans, C.; Kuhlthau, K.; MacDonald, S.; Yock, T. I.; Pulsifer, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tarbell, N. J.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 1091 BP S194 EP S194 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215302144 ER PT J AU Hong, TS Wo, JY McDonnell, EI Yeap, B Drapek, LC Wolfgang, JA Blaszkowsky, LS Kwak, EL Clark, J Tanguturi, S Goyal, L Allen, JN Ryan, DP Arellano, R Mullen, JT Mamon, HJ DeLaney, TF Zhu, AX AF Hong, T. S. Wo, J. Y. McDonnell, E. I. Yeap, B. Drapek, L. C. Wolfgang, J. A. Blaszkowsky, L. S. Kwak, E. L. Clark, J. Tanguturi, S. Goyal, L. Allen, J. N. Ryan, D. P. Arellano, R. Mullen, J. T. Mamon, H. J. DeLaney, T. F. Zhu, A. X. TI A Single Arm Phase 2 Study of Individualized Proton-Based Stereotactic Body Radiation Therapy (P-SBRT) of Liver Metastases SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Hong, T. S.; Wo, J. Y.; Wolfgang, J. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [McDonnell, E. I.; Yeap, B.; Drapek, L. C.; Blaszkowsky, L. S.; Kwak, E. L.; Clark, J.; Goyal, L.; Allen, J. N.; Ryan, D. P.; Arellano, R.; Mullen, J. T.; DeLaney, T. F.; Zhu, A. X.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tanguturi, S.] Harvard Radiat Oncol Program, Boston, MA USA. [Mamon, H. J.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 254 BP S112 EP S112 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301925 ER PT J AU Jagsi, R Griffith, KA Bellon, JR Woodward, WA Horton, JK Ho, AY Schott, A Pierce, LJ AF Jagsi, R. Griffith, K. A. Bellon, J. R. Woodward, W. A. Horton, J. K. Ho, A. Y. Schott, A. Pierce, L. J. TI TBCRC 024 Initial Results: A Multicenter Phase 1 Study of Veliparib Administered Concurrently With Chest Wall and Nodal Radiation Therapy in Patients With Inflammatory or Locoregionally Recurrent Breast Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Jagsi, R.; Griffith, K. A.; Schott, A.; Pierce, L. J.] Univ Michigan, Ann Arbor, MI 48109 USA. [Bellon, J. R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Woodward, W. A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Horton, J. K.] Duke Univ, Med Ctr, Durham, NC USA. [Ho, A. Y.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 312 BP S137 EP S137 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215302008 ER PT J AU Johung, KL Yeh, N Desai, NB Williams, TM Lautenschlaeger, T Arvold, ND Ning, M Attia, A Lovly, CM Goldberg, S Beal, K Yu, JB Kavanagh, BD Chiang, VL Camidge, DR Contessa, JN AF Johung, K. L. Yeh, N. Desai, N. B. Williams, T. M. Lautenschlaeger, T. Arvold, N. D. Ning, M. Attia, A. Lovly, C. M. Goldberg, S. Beal, K. Yu, J. B. Kavanagh, B. D. Chiang, V. L. Camidge, D. R. Contessa, J. N. TI Extended Survival and Prognostic Factors for Patients With ALK Rearranged NSCLC and Brain Metastasis SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Johung, K. L.; Goldberg, S.; Chiang, V. L.; Contessa, J. N.] Yale Univ, Sch Med, New Haven, CT USA. [Yeh, N.; Kavanagh, B. D.] Univ Colorado, Ctr Comprehens Canc, Aurora, CO USA. [Desai, N. B.; Beal, K.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Williams, T. M.] Ohio State Univ, Columbus, OH 43210 USA. [Arvold, N. D.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ning, M.; Lovly, C. M.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Attia, A.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Yu, J. B.] Yale Univ, Sch Med, New Haven, CT USA. [Camidge, D. R.] Univ Colorado, Aurora, CO USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 1050 BP S177 EP S177 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215302103 ER PT J AU Lee, JY Scarlett, S Daignault-Newton, S Sanda, MG Michalski, JM Sandler, HM Kuban, DA Zietman, AL Ciezki, JP Kaplan, ID McLaughlin, W Mantz, CA Finkelstein, SE Suy, S Collins, SP Hamstra, DA AF Lee, J. Y. Scarlett, S. Daignault-Newton, S. Sanda, M. G. Michalski, J. M. Sandler, H. M. Kuban, D. A. Zietman, A. L. Ciezki, J. P. Kaplan, I. D. McLaughlin, W. Mantz, C. A. Finkelstein, S. E. Suy, S. Collins, S. P. Hamstra, D. A. TI Impact of Rectal Bleeding on Quality of Life Measures After Prostate Radiation Therapy: Comparison of the EPIC-26 and EPIC-CP Instruments SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Lee, J. Y.; Scarlett, S.; Daignault-Newton, S.; Hamstra, D. A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Sanda, M. G.] Emory Univ, Atlanta, GA 30322 USA. [Michalski, J. M.] Washington Univ, Sch Med, St Louis, MO USA. [Sandler, H. M.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Kuban, D. A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Zietman, A. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Ciezki, J. P.] Cleveland Clin, Cleveland, OH 44106 USA. [Kaplan, I. D.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [McLaughlin, W.] Univ Michigan, Ann Arbor, MI 48109 USA. [Mantz, C. A.] 21st Century Oncol, Ft Myers, FL USA. [Finkelstein, S. E.] 21st Century Oncol, Scottsdale, AZ USA. [Suy, S.; Collins, S. P.] Georgetown Univ Hosp, Washington, DC 20007 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 1106 BP S201 EP S201 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215302159 ER PT J AU Li, PC Liebsch, NJ Niemierko, A Lessell, S Shih, HA AF Li, P. C. Liebsch, N. J. Niemierko, A. Lessell, S. Shih, H. A. TI Radiation Tolerance of the Optic Pathway After Fractionated Proton Radiation Therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Li, P. C.] Harvard Univ, Sch Med, Boston, MA USA. [Liebsch, N. J.; Niemierko, A.; Shih, H. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lessell, S.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 1032 BP S169 EP S169 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215302085 ER PT J AU Logie, N Jimenez, RB Pulenzas, N Linden, K Ciafone, D Ghosh, S Xu, Y Lefresne, S Wong, E Son, C Shih, HA Wong, WW Dennis, K Chow, E Fairchild, AM AF Logie, N. Jimenez, R. B. Pulenzas, N. Linden, K. Ciafone, D. Ghosh, S. Xu, Y. Lefresne, S. Wong, E. Son, C. Shih, H. A. Wong, W. W. Dennis, K. Chow, E. Fairchild, A. M. TI Recursive Partioning Analysis to Predict Survival for Patients Receiving Cranial Re-irradiation for Brain Metastases SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Logie, N.; Ghosh, S.; Fairchild, A. M.] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. [Jimenez, R. B.; Shih, H. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pulenzas, N.; Wong, E.] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Linden, K.; Xu, Y.; Dennis, K.] Ottawa Canc Ctr, Ottawa, ON, Canada. [Ciafone, D.; Wong, W. W.] Mayo Clin, Phoenix, AZ USA. [Lefresne, S.] BC Canc Agcy, Surrey, BC, Canada. [Son, C.] Univ Chicago, Chicago, IL 60637 USA. [Chow, E.] Univ Toronto, Toronto, ON, Canada. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 139 BP S62 EP S63 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301810 ER PT J AU Mak, KS Smith, AB Eidelman, A Clayman, RH Cheng, JS Matthews, J Niemierko, A Nielsen, ME Feldman, AS Lee, RJ Zietman, AL Shipley, WU Chen, RC Milowsky, MI Efstathiou, JA AF Mak, K. S. Smith, A. B. Eidelman, A. Clayman, R. H. Cheng, J. S. Matthews, J. Niemierko, A. Nielsen, M. E. Feldman, A. S. Lee, R. J. Zietman, A. L. Shipley, W. U. Chen, R. C. Milowsky, M. I. Efstathiou, J. A. TI Quality of Life in Long-term Survivors of Muscle-Invasive Bladder Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Mak, K. S.] Harvard Radiat Oncol Program, Boston, MA USA. [Smith, A. B.; Matthews, J.; Nielsen, M. E.; Milowsky, M. I.] Univ N Carolina, Chapel Hill, NC USA. [Eidelman, A.; Clayman, R. H.; Cheng, J. S.; Niemierko, A.; Feldman, A. S.; Lee, R. J.; Shipley, W. U.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Zietman, A. L.; Efstathiou, J. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Chen, R. C.] Univ N Carolina, Sch Med, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 50 BP S23 EP S23 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301721 ER PT J AU Miyamoto, DT Zheng, Y Wittner, B Lee, RJ Zhu, H Broderick, K Desai, R Brannigan, B Arora, K Dahl, DM Sequist, L Smith, MR Kapur, R Wu, CL Shioda, T Ramaswamy, S Ting, D Toner, M Maheswaran, S Haber, D AF Miyamoto, D. T. Zheng, Y. Wittner, B. Lee, R. J. Zhu, H. Broderick, K. Desai, R. Brannigan, B. Arora, K. Dahl, D. M. Sequist, L. Smith, M. R. Kapur, R. Wu, C. L. Shioda, T. Ramaswamy, S. Ting, D. Toner, M. Maheswaran, S. Haber, D. TI Single Cell RNA Profiling of Circulating Tumor Cells in Patients With Prostate Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Miyamoto, D. T.; Zheng, Y.; Wittner, B.; Lee, R. J.; Zhu, H.; Broderick, K.; Desai, R.; Brannigan, B.; Arora, K.; Dahl, D. M.; Sequist, L.; Smith, M. R.; Kapur, R.; Wu, C. L.; Shioda, T.; Ramaswamy, S.; Ting, D.; Toner, M.; Maheswaran, S.; Haber, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI bebarta, vikhyat/K-3476-2015 NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 237 BP S104 EP S104 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301908 ER PT J AU Mouw, K Amin-Mansour, A Braunstein, LZ Pike, J Damish, A Hornick, J D'Andrea, AD Van Allen, E Mamon, HJ AF Mouw, K. Amin-Mansour, A. Braunstein, L. Z. Pike, J. Damish, A. Hornick, J. D'Andrea, A. D. Van Allen, E. Mamon, H. J. TI Genomic Analysis of Chemoradiation Therapy Response in Anal Carcinoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Mouw, K.; Van Allen, E.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Amin-Mansour, A.; Van Allen, E.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Braunstein, L. Z.] Harvard Radiat Oncol Program, Boston, MA USA. [Pike, J.; Damish, A.; D'Andrea, A. D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hornick, J.; Mamon, H. J.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 284 BP S124 EP S125 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301955 ER PT J AU Paly, JJ Gray, PJ Lin, CC Sineshaw, H Jemal, A Efstathiou, JA AF Paly, J. J. Gray, P. J. Lin, C. C. Sineshaw, H. Jemal, A. Efstathiou, J. A. TI Management and Outcomes of Clinical Stage II A/B Seminoma: Results From the National Cancer Data Base SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Paly, J. J.; Gray, P. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lin, C. C.; Sineshaw, H.; Jemal, A.] Amer Canc Soc, Atlanta, GA 30329 USA. [Efstathiou, J. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 56 BP S26 EP S26 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301727 ER PT J AU Park, YK Sharp, GC Ye, SJ Winey, B AF Park, Y. K. Sharp, G. C. Ye, S. J. Winey, B. TI Early Experience in Cone Beam Projection Image Streaming for Real-Time Intrafractional Motion Monitoring Using a Conventional Linear Accelerator SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Park, Y. K.; Sharp, G. C.; Winey, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ye, S. J.] Seoul Natl Univ Hosp, Seoul 110744, South Korea. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 262 BP S115 EP S115 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301933 ER PT J AU Patel, VL Millington, T Sharp, GC Niemierko, A Yock, TI Choi, NC Hong, TS Mathisen, DJ Willers, H Gaissert, HA AF Patel, V. L. Millington, T. Sharp, G. C. Niemierko, A. Yock, T. I. Choi, N. C. Hong, T. S. Mathisen, D. J. Willers, H. Gaissert, H. A. TI Neoadjuvant IMRT with Chemotherapy for Esophageal Cancer Allows Cardiac Sparing Without Increasing Postoperative Pulmonary Complications SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Patel, V. L.; Millington, T.; Sharp, G. C.; Niemierko, A.; Yock, T. I.; Choi, N. C.; Mathisen, D. J.; Willers, H.; Gaissert, H. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hong, T. S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 31.5 BP S14 EP S15 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301702 ER PT J AU Prabhu, RS Feng, Y Landry, JC Cohen, SJ Staley, CA Whittington, R Sigurdson, ER Nimeiri, H Verma, U Benson, AB AF Prabhu, R. S. Feng, Y. Landry, J. C. Cohen, S. J. Staley, C. A. Whittington, R. Sigurdson, E. R. Nimeiri, H. Verma, U. Benson, A. B. TI Phase 2 Trial of Preoperative Radiation With Concurrent Capecitabine, Oxaliplatin, and Bevacizumab Followed by Surgery and Postoperative 5-FU, Leucovorin, Oxaliplatin (FOLFOX), and Bevacizumab in Patients With Locally Advanced Rectal Cancer: ECOG 3204 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Prabhu, R. S.] Levine Canc Inst, Southeast Radiat Oncol Grp, Charlotte, NC USA. [Feng, Y.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Landry, J. C.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Cohen, S. J.; Sigurdson, E. R.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Staley, C. A.] Winship Canc Inst, Atlanta, GA USA. [Whittington, R.] VA New Jersey Hlth Care Syst, E Orange, NJ USA. [Nimeiri, H.; Benson, A. B.] Northwestern Univ, Chicago, IL 60611 USA. [Verma, U.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 289 BP S126 EP S127 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301960 ER PT J AU Racsa, M Jones, JA Dharmarajan, KV Spektor, A Noveroske, S Wei, RL Balboni, TA AF Racsa, M. Jones, J. A. Dharmarajan, K. V. Spektor, A. Noveroske, S. Wei, R. L. Balboni, T. A. TI Palliative Care Training in Radiation Oncology: A National Survey SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Racsa, M.; Spektor, A.; Noveroske, S.; Balboni, T. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jones, J. A.] Univ Penn, Philadelphia, PA 19104 USA. [Dharmarajan, K. V.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Wei, R. L.] Univ Calif Irvine, Orange, CA 92668 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 137 BP S61 EP S62 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301808 ER PT J AU Raldow, A Recht, A Sher, DJ Punglia, RS AF Raldow, A. Recht, A. Sher, D. J. Punglia, R. S. TI Cost-Effectiveness of the Oncotype DX DCIS Score SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Raldow, A.] Harvard Radiat Oncol Program, Boston, MA USA. [Recht, A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Sher, D. J.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Punglia, R. S.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 204 BP S90 EP S91 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301876 ER PT J AU Schuemann, JP Lin, Y Paganetti, H McMahon, SJ AF Schuemann, J. P. Lin, Y. Paganetti, H. McMahon, S. J. TI Effects of Gold Nanoparticles for Radiation Therapy Enhancement SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Schuemann, J. P.; Lin, Y.; McMahon, S. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Paganetti, H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 95 BP S43 EP S43 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301766 ER PT J AU Sperduto, PW Yang, TJ Beal, K Pan, HY Brown, PD Ho, YY Yeh, N Gaspar, LE Braunstein, SE Sneed, PK Boyle, JM Kirkpatrick, JP Mak, KS Shih, HA Engelman, A Roberge, D Arvold, ND Yu, JB Hardie, JG Mehta, MP AF Sperduto, P. W. Yang, T. J. Beal, K. Pan, H. Y. Brown, P. D. Ho, Y. Y. Yeh, N. Gaspar, L. E. Braunstein, S. E. Sneed, P. K. Boyle, J. M. Kirkpatrick, J. P. Mak, K. S. Shih, H. A. Engelman, A. Roberge, D. Arvold, N. D. Yu, J. B. Hardie, J. G. Mehta, M. P. TI The Effect of Gene Mutations on Survival in Patients With Adenocarcinoma of the Lung Following the Development of Brain Metastases SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Sperduto, P. W.] Minneapolis Radiat Oncol PA, Minneapolis, MN USA. [Sperduto, P. W.] Univ Minnesota, Med Ctr, Gamma Knife Ctr, Minneapolis, MN 55455 USA. [Yang, T. J.; Beal, K.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Pan, H. Y.; Brown, P. D.; Ho, Y. Y.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Ho, Y. Y.] Univ Minnesota, Minneapolis, MN USA. [Yeh, N.] Univ Colorado, Ctr Comprehens Canc, Aurora, CO USA. [Gaspar, L. E.] Univ Colorado Denver, Aurora, CO USA. [Braunstein, S. E.; Sneed, P. K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Boyle, J. M.; Kirkpatrick, J. P.] Duke Univ, Med Ctr, Durham, NC USA. [Mak, K. S.; Shih, H. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Engelman, A.] Univ Maryland, Baltimore, MD 21201 USA. [Roberge, D.] Ctr Hosp Univ Montreal, Montreal, PQ, Canada. [Arvold, N. D.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Yu, J. B.] Yale Univ, New Haven, CT USA. [Hardie, J. G.] Mayo Clin, Rochester, MN USA. [Mehta, M. P.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 83 BP S37 EP S38 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301754 ER PT J AU Taghian, AG Ferguson, C Swaroop, M Horick, N Skolny, M Miller, C Brunelle, C Jammallo, L O'Toole, J Specht, M AF Taghian, A. G. Ferguson, C. Swaroop, M. Horick, N. Skolny, M. Miller, C. Brunelle, C. Jammallo, L. O'Toole, J. Specht, M. TI Impact of Ipsilateral Blood Pressure Measurements, Blood Draws, Infusions, and Air Travel on the Risk of Lymphedema for Patients Treated for Breast Cancer: A Prospective Study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Taghian, A. G.; Ferguson, C.; Swaroop, M.; Horick, N.; Skolny, M.; Miller, C.; Brunelle, C.; Jammallo, L.; O'Toole, J.; Specht, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 241 BP S106 EP S106 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301912 ER PT J AU Tanguturi, S Ramkissoon, S Horvath, MC Reardon, DA Lindeman, N Ligon, AH Trippa, L Wen, P Ligon, KL Alexander, BM AF Tanguturi, S. Ramkissoon, S. Horvath, M. C. Reardon, D. A. Lindeman, N. Ligon, A. H. Trippa, L. Wen, P. Ligon, K. L. Alexander, B. M. TI Survival Outcomes in Genetic Subgroups of Glioblastoma: Implications for Trial Design SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Tanguturi, S.] Harvard Radiat Oncol Program, Boston, MA USA. [Ramkissoon, S.; Lindeman, N.; Ligon, A. H.; Ligon, K. L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Horvath, M. C.; Reardon, D. A.; Trippa, L.; Wen, P.; Alexander, B. M.] Brigham & Womens Canc Ctr, Dana Farber Canc Inst, Boston, MA USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 323 BP S142 EP S142 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215302019 ER PT J AU Tao, R Krishnan, S Bhosale, P Javle, M Shroff, R Kaseb, A Jensen, G Bishop, AJ Swanick, CW Koay, EJ Thames, HD Hong, TS Das, P Crane, CH AF Tao, R. Krishnan, S. Bhosale, P. Javle, M. Shroff, R. Kaseb, A. Jensen, G. Bishop, A. J. Swanick, C. W. Koay, E. J. Thames, H. D. Hong, T. S. Das, P. Crane, C. H. TI Ablative Radiation Therapy Doses Lead to a Substantial Prolongation of Survival in Patients With Inoperable Intrahepatic Cholangiocarcinoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Tao, R.; Krishnan, S.; Bhosale, P.; Javle, M.; Shroff, R.; Kaseb, A.; Jensen, G.; Bishop, A. J.; Swanick, C. W.; Koay, E. J.; Thames, H. D.; Das, P.; Crane, C. H.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Hong, T. S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 256 BP S113 EP S113 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301927 ER PT J AU Tendulkar, RD Agrawal, S Efstathiou, JA Pisansky, TM Michalski, JM Koontz, BF Hamstra, DA Feng, FY Liauw, S Abramowitz, MC Pollack, A Anscher, MS Moghanaki, D Den, RB Stephans, KL Kattan, M Stephenson, AJ AF Tendulkar, R. D. Agrawal, S. Efstathiou, J. A. Pisansky, T. M. Michalski, J. M. Koontz, B. F. Hamstra, D. A. Feng, F. Y. Liauw, S. Abramowitz, M. C. Pollack, A. Anscher, M. S. Moghanaki, D. Den, R. B. Stephans, K. L. Kattan, M. Stephenson, A. J. TI Contemporary Update of a Multi-institutional Predictive Nomogram for Salvage Radiation Therapy After Prostatectomy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Tendulkar, R. D.; Stephans, K. L.; Kattan, M.; Stephenson, A. J.] Cleveland Clin, Cleveland, OH 44106 USA. [Agrawal, S.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA. [Efstathiou, J. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Pisansky, T. M.] Mayo Clin, Rochester, MN USA. [Michalski, J. M.] Washington Univ, Sch Med, St Louis, MO USA. [Koontz, B. F.] Duke Univ, Med Ctr, Durham, NC USA. [Hamstra, D. A.; Feng, F. Y.] Univ Michigan, Ann Arbor, MI 48109 USA. [Liauw, S.] Univ Chicago, Chicago, IL 60637 USA. [Abramowitz, M. C.; Pollack, A.] Univ Miami, Miami, FL USA. [Anscher, M. S.; Moghanaki, D.] Virginia Commonwealth Univ, Med Ctr, Richmond, VA USA. [Den, R. B.] Thomas Jefferson Univ, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 300 BP S131 EP S131 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301971 ER PT J AU Underwood, TSA Giantsoudi, D Moteabbed, M Zietman, AL Efstathiou, JA Paganetti, H Lu, HM AF Underwood, T. S. A. Giantsoudi, D. Moteabbed, M. Zietman, A. L. Efstathiou, J. A. Paganetti, H. Lu, H. M. TI Protons for Prostate: Seeking Benefit via Anterior Beam Angles SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Underwood, T. S. A.; Giantsoudi, D.; Moteabbed, M.; Zietman, A. L.; Efstathiou, J. A.; Paganetti, H.; Lu, H. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Underwood, T. S. A.] UCL, London, England. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 1144 BP S215 EP S215 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215302195 ER PT J AU Vatner, R Shin, S Legault, G Rosman, M Weyman, E Chan, S Yeh, BK MacDonald, S Tarbell, NJ Allen, J Yock, TI AF Vatner, R. Shin, S. Legault, G. Rosman, M. Weyman, E. Chan, S. Yeh, B. K. MacDonald, S. Tarbell, N. J. Allen, J. Yock, T. I. TI Comparison of Endocrine Dysfunction and Dosimetry in Pediatric Patients Treated With Proton Versus Photon Radiation Therapy for Medulloblastoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Vatner, R.; Shin, S.; Rosman, M.; Yeh, B. K.] NYU, Sch Med, New York, NY USA. [Shin, S.; Yeh, B. K.; Allen, J.] New York Univ, Langone Med Ctr, New York, NY USA. [Legault, G.] Montreal Childrens Hosp, Montreal, PQ H3H 1P3, Canada. [Legault, G.] CHU Sherbrooke, Sherbrooke, PQ J1H 5N4, Canada. [Weyman, E.; Chan, S.; MacDonald, S.; Yock, T. I.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Tarbell, N. J.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 72 BP S32 EP S33 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301743 ER PT J AU Vega, RM Formenti, SC MacDonald, S AF Vega, R. Mailhot Formenti, S. C. MacDonald, S. TI Cost-Effective Analysis of Proton Therapy for Breast Irradiation SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Vega, R. Mailhot; Formenti, S. C.] NYU, Sch Med, New York, NY USA. [MacDonald, S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 205 BP S91 EP S91 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301877 ER PT J AU Vieira, BL Kosak, TK Belkacemi, Y Wo, JY Zhu, AX Hong, TS Wolfgang, JA AF Vieira, B. Lavajo Kosak, T. K. Belkacemi, Y. Wo, J. Y. Zhu, A. X. Hong, T. S. Wolfgang, J. A. TI Interfractional and Immobilization Related Respiratory Motion Variability for Treatment of Liver Tumors SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Vieira, B. Lavajo; Belkacemi, Y.] AROME Assoc Radiotherapy & Oncol Mediterranean A, Paris, France. [Vieira, B. Lavajo; Kosak, T. K.; Wo, J. Y.; Zhu, A. X.; Hong, T. S.; Wolfgang, J. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Belkacemi, Y.] Henri Mondor Univ Hosp, Creteil, France. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 263 BP S115 EP S116 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301934 ER PT J AU Warren, L Guo, H Regan, MM Nakhlis, F Yeh, ED Jacene, HA Hirshfield-Bartik, J Overmoyer, BA Bellon, JR AF Warren, L. Guo, H. Regan, M. M. Nakhlis, F. Yeh, E. D. Jacene, H. A. Hirshfield-Bartik, J. Overmoyer, B. A. Bellon, J. R. TI Inflammatory Breast Cancer and Brain Metastases: Risk Factors and Outcomes SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Warren, L.] Harvard Radiat Oncol Program, Boston, MA USA. [Guo, H.; Regan, M. M.; Nakhlis, F.; Yeh, E. D.; Jacene, H. A.; Hirshfield-Bartik, J.; Overmoyer, B. A.; Bellon, J. R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nakhlis, F.; Yeh, E. D.; Jacene, H. A.; Hirshfield-Bartik, J.; Overmoyer, B. A.; Bellon, J. R.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 1167 BP S224 EP S224 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215302217 ER PT J AU Warren, L Ligibel, JA Chen, YH Catalano, PJ Bellon, JR AF Warren, L. Ligibel, J. A. Chen, Y. H. Catalano, P. J. Bellon, J. R. TI The Impact of Body Mass Index on Locoregional Recurrence in Women With Early-Stage Breast Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Warren, L.] Harvard Radiat Oncol Program, Boston, MA USA. [Ligibel, J. A.; Chen, Y. H.; Catalano, P. J.; Bellon, J. R.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 311 BP S137 EP S137 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215302007 ER PT J AU Wei, X Komaki, RU Choi, NC O'Reilly, MS Fossella, FV Chang, JY Gomez, DR Nguyen, Q Pisters, KM Tsao, A Massarelli, E Zhuang, Y Xu, T Hernandez, M Mohan, R Liao, Z AF Wei, X. Komaki, R. U. Choi, N. C. O'Reilly, M. S. Fossella, F. V. Chang, J. Y. Gomez, D. R. Nguyen, Q. Pisters, K. M. Tsao, A. Massarelli, E. Zhuang, Y. Xu, T. Hernandez, M. Mohan, R. Liao, Z. TI Radiation Dose-Escalation to the Gross Tumor Volume Using Simultaneous Integrated Boost Intensity Modulated Photon or Proton Therapy With Concurrent Chemotherapy for Stage II-III Non-Small Cell Lung Cancer: A Preliminary Report of a Phase 1 Protocol SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Wei, X.; Komaki, R. U.; O'Reilly, M. S.; Fossella, F. V.; Chang, J. Y.; Gomez, D. R.; Nguyen, Q.; Pisters, K. M.; Tsao, A.; Massarelli, E.; Zhuang, Y.; Xu, T.; Hernandez, M.; Mohan, R.; Liao, Z.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Choi, N. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 199 BP S88 EP S88 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301870 ER PT J AU Winey, B Al-Halabi, H DeLaney, TF Guckenberger, M Mantel, F Sheehan, JP Schlesinger, D Quan, K Gerszten, PC Flickinger, JC Shin, J Oh, KS AF Winey, B. Al-Halabi, H. DeLaney, T. F. Guckenberger, M. Mantel, F. Sheehan, J. P. Schlesinger, D. Quan, K. Gerszten, P. C. Flickinger, J. C., Sr. Shin, J. Oh, K. S. TI Variability of Spinal Cord Definition Using MR T2 Versus CT Myelography for Spine Radiosurgery SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Winey, B.; DeLaney, T. F.; Shin, J.; Oh, K. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Winey, B.; DeLaney, T. F.; Shin, J.; Oh, K. S.] Harvard Univ, Sch Med, Boston, MA USA. [Al-Halabi, H.] Montreal Gen Hosp, Montreal, PQ H3G 1A4, Canada. [Al-Halabi, H.] McGill Univ, Montreal, PQ, Canada. [Guckenberger, M.] Univ Zurich, Zurich, Switzerland. [Mantel, F.] Univ Hosp Wurzburg, Wurzburg, Germany. [Sheehan, J. P.; Schlesinger, D.] Univ Virginia, Charlottesville, VA USA. [Quan, K.; Flickinger, J. C., Sr.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. [Gerszten, P. C.] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 1008 BP S159 EP S160 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215302061 ER PT J AU Wo, JY Zhu, AX McDonnell, EI Yeap, B Borger, DR Iafrate, A Drapek, LC Blaszkowsky, LS Kwak, EL Clark, J Goyal, L Allen, JN Ryan, DP Arellano, R Wolfgang, JA Mullen, JT Mamon, HJ DeLaney, TF Hong, TS AF Wo, J. Y. Zhu, A. X. McDonnell, E. I. Yeap, B. Borger, D. R. Iafrate, A. Drapek, L. C. Blaszkowsky, L. S. Kwak, E. L. Clark, J. Goyal, L. Allen, J. N. Ryan, D. P. Arellano, R. Wolfgang, J. A. Mullen, J. T. Mamon, H. J. DeLaney, T. F. Hong, T. S. TI Clinical and Molecular Predictors of Local Failure After SBRT for Liver Metastases: A Secondary Analysis of a Prospective Phase II Trial SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Wo, J. Y.; Wolfgang, J. A.; Hong, T. S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Zhu, A. X.; McDonnell, E. I.; Yeap, B.; Borger, D. R.; Iafrate, A.; Drapek, L. C.; Blaszkowsky, L. S.; Kwak, E. L.; Clark, J.; Goyal, L.; Allen, J. N.; Ryan, D. P.; Arellano, R.; Mullen, J. T.; DeLaney, T. F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mamon, H. J.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 253 BP S111 EP S112 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301924 ER PT J AU Yang, TJ Wang, DG Pauli, C Loughran, RM Kim, H Zhang, T Annamalai, D Emerling, BM Powell, SN Gray, NS Cantley, LC AF Yang, T. J. Wang, D. G. Pauli, C. Loughran, R. M. Kim, H. Zhang, T. Annamalai, D. Emerling, B. M. Powell, S. N. Gray, N. S. Cantley, L. C. TI Inhibition of Phosphatidylinositol-5-Phosphate 4-Kinases (PI5P4K alpha and beta) Inhibits Proliferation and Radiosensitizes Triple Negative Breast Cancer Cells Harboring p53 Mutations SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Yang, T. J.; Annamalai, D.; Powell, S. N.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Wang, D. G.; Pauli, C.; Loughran, R. M.; Emerling, B. M.; Cantley, L. C.] Weill Cornell Med Coll, New York, NY USA. [Kim, H.] Harvard Univ, Sch Med, Boston, MA USA. [Zhang, T.; Gray, N. S.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 110 BP S49 EP S50 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301781 ER PT J AU Yip, S Coroller, T Niu, NN Mamon, HJ Aerts, H Berbeco, RI AF Yip, S. Coroller, T. Niu, N. N. Mamon, H. J. Aerts, H. Berbeco, R. I. TI Local Textural Feature Changes as Predictors of Pathologic Response in Esophageal Cancer Patients SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Yip, S.; Coroller, T.; Aerts, H.; Berbeco, R. I.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Yip, S.; Coroller, T.; Aerts, H.; Berbeco, R. I.] Harvard Univ, Sch Med, Boston, MA USA. [Niu, N. N.] Harvard Radiat Oncol Program, Boston, MA USA. [Mamon, H. J.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 91 BP S41 EP S41 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215301762 ER PT J AU Zhao, SG Jackson, W Kothari, V Schipper, M Erho, N Evans, JR Speers, C Hamstra, DA Niknafs, YS Nguyen, PL Schaeffer, EM Ross, AE Den, RB Klein, EA Jenkins, RB Davicioni, E Feng, FY AF Zhao, S. G. Jackson, W. Kothari, V. Schipper, M. Erho, N. Evans, J. R. Speers, C. Hamstra, D. A. Niknafs, Y. S. Nguyen, P. L. Schaeffer, E. M. Ross, A. E. Den, R. B. Klein, E. A. Jenkins, R. B. Davicioni, E. Feng, F. Y. TI High- Throughput Transcriptomic Analysis Nominates Proteasomal Genes As Age Specific Biomarkers and Therapeutic Targets in Prostate Cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) CY OCT 18-21, 2015 CL San Antonio, TX SP Amer Soc Radiat Oncol C1 [Zhao, S. G.; Jackson, W.; Kothari, V.; Schipper, M.; Evans, J. R.; Hamstra, D. A.; Niknafs, Y. S.; Feng, F. Y.] Univ Michigan, Ann Arbor, MI 48109 USA. [Erho, N.; Davicioni, E.] GenomeDx Biosci, Vancouver, BC, Canada. [Speers, C.] Univ Michigan, Ann Arbor, MI 48109 USA. [Nguyen, P. L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nguyen, P. L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Schaeffer, E. M.] Johns Hopkins Univ, Baltimore, MD USA. [Ross, A. E.] Johns Hopkins Sch Med, Baltimore, MD USA. [Den, R. B.] Thomas Jefferson Univ, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA. [Klein, E. A.] Cleveland Clin, Cleveland, OH 44106 USA. [Jenkins, R. B.] Mayo Clin, Rochester, MN USA. NR 0 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2015 VL 93 IS 3 SU S MA 325 BP S143 EP S143 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DI0VL UT WOS:000373215302021 ER PT J AU Alterovitz, G Warner, J Zhang, PJ Chen, YS Ullman-Cullere, M Kreda, D Kohane, IS AF Alterovitz, Gil Warner, Jeremy Zhang, Peijin Chen, Yishen Ullman-Cullere, Mollie Kreda, David Kohane, Isaac S. TI SMART on FHIR Genomics: facilitating standardized clinico-genomic apps SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article DE genomics; data sharing; clinicogenomics; data warehouse; i2b2; SMART; FHIR; HL7; standards; EMR; EHR ID NOMENCLATURE; CONSORTIUM AB Background Supporting clinical decision support for personalized medicine will require linking genome and phenome variants to a patient's electronic health record (EHR), at times on a vast scale. Clinico-genomic data standards will be needed to unify how genomic variant data are accessed from different sequencing systems. Methods A specification for the basis of a clinic-genomic standard, building upon the current Health Level Seven International Fast Healthcare Interoperability Resources (FHIRA (R)) standard, was developed. An FHIR application protocol interface (API) layer was attached to proprietary sequencing platforms and EHRs in order to expose gene variant data for presentation to the end-user. Three representative apps based on the SMART platform were built to test end-to-end feasibility, including integration of genomic and clinical data. Results Successful design, deployment, and use of the API was demonstrated and adopted by HL7 Clinical Genomics Workgroup. Feasibility was shown through development of three apps by various types of users with background levels and locations. Conclusion This prototyping work suggests that an entirely data (and web) standards-based approach could prove both effective and efficient for advancing personalized medicine. C1 [Alterovitz, Gil; Kohane, Isaac S.] Childrens Hosp Informat Program, Boston, MA USA. [Alterovitz, Gil; Kreda, David; Kohane, Isaac S.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA USA. [Alterovitz, Gil; Kohane, Isaac S.] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Warner, Jeremy] Vanderbilt Univ, Dept Biomed Informat, 221 Kirkland Hall, Nashville, TN 37235 USA. [Warner, Jeremy] Vanderbilt Univ, Dept Med, Div Hematol Oncol, Nashville, TN USA. [Zhang, Peijin] Carnegie Mellon Univ, Dept Comp Sci, Pittsburgh, PA 15213 USA. [Chen, Yishen] Univ Illinois, Dept Comp Sci, Champaign, IL USA. [Ullman-Cullere, Mollie] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Alterovitz, G (reprint author), 10 Shattuck St,311B, Boston, MA 02115 USA. EM ga@alum.mit.edu FU Strategic Health IT Advanced Research Projects Award from Office of the National Coordinator of Health Information Technology [90TR000101] FX This work was supported by the Strategic Health IT Advanced Research Projects Award 90TR000101 from the Office of the National Coordinator of Health Information Technology. NR 16 TC 12 Z9 12 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1067-5027 EI 1527-974X J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD NOV PY 2015 VL 22 IS 6 BP 1173 EP 1178 DI 10.1093/jamia/ocv045 PG 6 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA DI8AF UT WOS:000373722400013 PM 26198304 ER PT J AU Shirts, BH Salama, JS Aronson, SJ Chung, WK Gray, SW Hindorff, LA Jarvik, GP Plon, SE Stoffel, EM Tarczy-Hornoch, PZ Van Allen, EM Weck, KE Chute, CG Freimuth, RR Grundmeier, RW Hartzler, AL Li, RL Peissig, PL Peterson, JF Rasmussen, LV Starren, JB Williams, MS Overby, CL AF Shirts, Brian H. Salama, Joseph S. Aronson, Samuel J. Chung, Wendy K. Gray, Stacy W. Hindorff, Lucia A. Jarvik, Gail P. Plon, Sharon E. Stoffel, Elena M. Tarczy-Hornoch, Peter Z. Van Allen, Eliezer M. Weck, Karen E. Chute, Christopher G. Freimuth, Robert R. Grundmeier, Robert W. Hartzler, Andrea L. Li, Rongling Peissig, Peggy L. Peterson, Josh F. Rasmussen, Luke V. Starren, Justin B. Williams, Marc S. Overby, Casey L. TI CSER and eMERGE: current and potential state of the display of genetic information in the electronic health record SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article DE genetics; electronic health records; translational research; clinical decision support; survey ID CLINICAL DECISION-SUPPORT; GENOMIC DATA; INDIVIDUALIZED MEDICINE; PERSONALIZED MEDICINE; TECHNICAL DESIDERATA; IMPLEMENTATION; PHARMACOGENOMICS; INTEGRATION; CHALLENGES; ATTITUDES AB Objective Clinicians' ability to use and interpret genetic information depends upon how those data are displayed in electronic health records (EHRs). There is a critical need to develop systems to effectively display genetic information in EHRs and augment clinical decision support (CDS). Materials and Methods The National Institutes of Health (NIH)-sponsored Clinical Sequencing Exploratory Research and Electronic Medical Records & Genomics EHR Working Groups conducted a multiphase, iterative process involving working group discussions and 2 surveys in order to determine how genetic and genomic information are currently displayed in EHRs, envision optimal uses for different types of genetic or genomic information, and prioritize areas for EHR improvement. Results There is substantial heterogeneity in how genetic information enters and is documented in EHR systems. Most institutions indicated that genetic information was displayed in multiple locations in their EHRs. Among surveyed institutions, genetic information enters the EHR through multiple laboratory sources and through clinician notes. For laboratory-based data, the source laboratory was the main determinant of the location of genetic information in the EHR. The highest priority recommendation was to address the need to implement CDS mechanisms and content for decision support for medically actionable genetic information. Conclusion Heterogeneity of genetic information flow and importance of source laboratory, rather than clinical content, as a determinant of information representation are major barriers to using genetic information optimally in patient care. Greater effort to develop interoperable systems to receive and consistently display genetic and/or genomic information and alert clinicians to genomic-dependent improvements to clinical care is recommended. C1 [Shirts, Brian H.] Univ Washington, Dept Lab Med, Box 357110,1959 NE Pacific St,NW120, Seattle, WA 98195 USA. [Salama, Joseph S.; Jarvik, Gail P.] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. [Aronson, Samuel J.] Partners Healthcare, Personalized Med, Boston, MA USA. [Chung, Wendy K.] Columbia Univ, Dept Pediat, Med Ctr, New York, NY 10027 USA. [Gray, Stacy W.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Gray, Stacy W.; Van Allen, Eliezer M.] Dana Farber Canc Inst, Boston, MA USA. [Hindorff, Lucia A.; Li, Rongling] NHGRI, NIH, Rockville, MD USA. [Jarvik, Gail P.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Plon, Sharon E.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Stoffel, Elena M.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Tarczy-Hornoch, Peter Z.] Univ Washington, Dept Biomed Informat & Med Educ, Seattle, WA 98195 USA. [Van Allen, Eliezer M.] Broad Inst MIT & Harvard, Cambridge, MA USA. [Weck, Karen E.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC USA. [Weck, Karen E.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Chute, Christopher G.; Freimuth, Robert R.] Mayo Clin, Div Biomed Stat & Informat, Dept Hlth Sci Res, Rochester, MN USA. [Freimuth, Robert R.] Childrens Hosp Philadelphia, Dept Biomed & Hlth Informat, Philadelphia, PA 19104 USA. [Hartzler, Andrea L.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Peissig, Peggy L.] Marshfield Clin Res Fdn, Biomed Informat Res Ctr, Marshfield, WI USA. [Peterson, Josh F.] Dept Biomed Informat, Nashville, TN USA. [Rasmussen, Luke V.; Starren, Justin B.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Div Hlth & Biomed Informat, Chicago, IL 60611 USA. [Williams, Marc S.; Overby, Casey L.] Geisinger Med Ctr, Genome Med Inst, Danville, PA 17822 USA. [Overby, Casey L.] Univ Maryland, Sch Med, Program Personalized & Genom Med, Dept Med, Baltimore, MD 21201 USA. [Overby, Casey L.] Univ Maryland, Sch Med, Ctr Health Related Informat & Bioimaging, Baltimore, MD 21201 USA. RP Shirts, BH (reprint author), Univ Washington, Dept Lab Med, Box 357110,1959 NE Pacific St,NW120, Seattle, WA 98195 USA. EM shirtsb@uw.edu OI Rasmussen, Luke/0000-0002-4497-8049; Overby, Casey/0000-0001-9302-5968; Tarczy-Hornoch, Peter/0000-0003-1047-179X FU NHGRI; NCI [U01 HG006485, U01 HG006500, U01 HG006546, R01 HG006600, U01 HG006492, UM1 HG007301, UM1 HG007292, UM1 HG006508, U01 HG006487, U01 HG006507, U01 HG007307]; National Human Genome Research Institute [U01HG006828, U01HG006830, U01HG006389, U01HG006382, U01HG006375, U01HG006379, U01HG006380, U01HG006388, U01HG006378, U01HG006385] FX CSER: The Clinical Sequencing Exploratory Research Program (CSER) was initiated and funded by NHGRI and the NCI through the following grants: U01 HG006485 (Baylor College of Medicine); U01 HG006500 (Brigham & Women's Hospital); U01 HG006546 (Children's Hospital of Philadelphia); R01 HG006600 (Columbia University); U01 HG006492 (Dana-Farber Cancer Institute); UM1 HG007301 (HudsonAlpha Institute); UM1 HG007292 (Kaiser Permanente); UM1 HG006508 (University of Michigan); U01 HG006487 (University of North Carolina); U01 HG006507 (University of Washington); and U01 HG007307 (University of Washington serving as the Coordinating Center).; eMERGE: The eMERGE Network was initiated and funded by National Human Genome Research Institute through the following grants: U01HG006828 (Cincinnati Children's Hospital Medical Center/Boston Children's Hospital); U01HG006830 (Children's Hospital of Philadelphia); U01HG006389 (Essentia Institute of Rural Health); U01HG006382 (Geisinger Clinic); U01HG006375 (Group Health Cooperative); U01HG006379 (Mayo Clinic); U01HG006380 (Icahn School of Medicine at Mount Sinai); U01HG006388 (Northwestern University); U01HG006378 (Vanderbilt University Medical Center); and U01HG006385 (Vanderbilt University Medical Center serving as the Coordinating Center). NR 35 TC 9 Z9 9 U1 4 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1067-5027 EI 1527-974X J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD NOV PY 2015 VL 22 IS 6 BP 1231 EP 1242 DI 10.1093/jamia/ocv065 PG 12 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics SC Computer Science; Health Care Sciences & Services; Information Science & Library Science; Medical Informatics GA DI8AF UT WOS:000373722400021 PM 26142422 ER PT J AU Aaronson, EL Wittels, KA Nadel, ES Schuur, JD AF Aaronson, Emily L. Wittels, Kathleen A. Nadel, Eric S. Schuur, Jeremiah D. TI Morbidity and Mortality Conference in Emergency Medicine Residencies and the Culture of Safety SO WESTERN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID ERRORS; SYSTEM AB Introduction: Morbidity and mortality conferences (M+M) are a traditional part of residency training and mandated by the Accreditation Counsel of Graduate Medical Education. This study's objective was to determine the goals, structure, and the prevalence of practices that foster strong safety cultures in the M+Ms of U.S. emergency medicine (EM) residency programs. Methods: The authors conducted a national survey of U.S. EM residency program directors. The survey instrument evaluated five domains of M+M (Organization and Infrastructure; Case Finding; Case Selection; Presentation; and Follow up) based on the validated Agency for Healthcare Research & Quality Safety Culture survey. Results: There was an 80% (151/188) response rate. The primary objectives of M+M were discussing adverse outcomes (53/151, 35%), identifying systems errors (47/151, 31%) and identifying cognitive errors (26/151, 17%). Fifty-six percent (84/151) of institutions have anonymous case submission, with 10% (15/151) maintaining complete anonymity during the presentation and 21% (31/151) maintaining partial anonymity. Forty-seven percent (71/151) of programs report a formal process to follow up on systems issues identified at M+M. Forty-four percent (67/151) of programs report regular debriefing with residents who have had their cases presented. Conclusion: The structure and goals of M+Ms in EM residencies vary widely. Many programs lack features of M+M that promote a non-punitive response to error, such as anonymity. Other programs lack features that support strong safety cultures, such as following up on systems issues or reporting back to residents on improvements. Further research is warranted to determine if M+M structure is related to patient safety culture in residency programs. C1 [Aaronson, Emily L.; Wittels, Kathleen A.; Nadel, Eric S.; Schuur, Jeremiah D.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. [Aaronson, Emily L.; Nadel, Eric S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Wittels, Kathleen A.; Nadel, Eric S.; Schuur, Jeremiah D.] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA USA. RP Aaronson, EL (reprint author), Massachusetts Gen Hosp, Zero Emerson Pl,Suite 3B, Boston, MA 02114 USA. EM eaaronson@partners.org NR 21 TC 0 Z9 0 U1 0 U2 0 PU WESTJEM PI ORANGE PA C/O SHAHRAM LOTFIPOUR, MD, MPH, 333 CITY BLVD W STE 640, RT 128-01, ORANGE, CA 92868 USA SN 1936-900X EI 1936-9018 J9 WEST J EMERG MED JI West. J. Emerg. Med. PD NOV PY 2015 VL 16 IS 6 SI SI BP 810 EP 817 DI 10.5811/westjem.2015.8.26559 PG 8 WC Emergency Medicine SC Emergency Medicine GA DH9OG UT WOS:000373124900004 PM 26594271 ER PT J AU Bentley, S Mudan, G Strother, C Wong, N AF Bentley, Suzanne Mudan, Gurpreet Strother, Christopher Wong, Nelson TI Are Live Ultrasound Models Replaceable? Traditional versus Simulated Education Module for FAST Exam SO WESTERN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID MILESTONES; EXPERIENCE; TRAUMA AB Introduction: The focused assessment with sonography for trauma (FAST) is a commonly used and life-saving tool in the initial assessment of trauma patients. The recommended emergency medicine (EM) curriculum includes ultrasound and studies show the additional utility of ultrasound training for medical students. EM clerkships vary and often do not contain formal ultrasound instruction. Time constraints for facilitating lectures and hands-on learning of ultrasound are challenging. Limitations on didactics call for development and inclusion of novel educational strategies, such as simulation. The objective of this study was to compare the test, survey, and performance of ultrasound between medical students trained on an ultrasound simulator versus those trained via traditional, hands-on patient format. Methods: This was a prospective, blinded, controlled educational study focused on EM clerkship medical students. After all received a standardized lecture with pictorial demonstration of image acquisition, students were randomized into two groups: control group receiving traditional training method via practice on a human model and intervention group training via practice on an ultrasound simulator. Participants were tested and surveyed on indications and interpretation of FAST and training and confidence with image interpretation and acquisition before and after this educational activity. Evaluation of FAST skills was performed on a human model to emulate patient care and practical skills were scored via objective structured clinical examination (OSCE) with critical action checklist. Results: There was no significant difference between control group (N=54) and intervention group (N=39) on pretest scores, prior ultrasound training/education, or ultrasound comfort level in general or on FAST. All students (N=93) showed significant improvement from pre-to post-test scores and significant improvement in comfort level using ultrasound in general and on FAST (p<0.001). There was no significant difference between groups on OSCE scores of FAST on a live model. Overall, no differences were demonstrated between groups trained on human models versus simulator. Discussion: There was no difference between groups in knowledge based ultrasound test scores, survey of comfort levels with ultrasound, and students' abilities to perform and interpret FAST on human models. Conclusion: These findings suggest that an ultrasound simulator is a suitable alternative method for ultrasound education. Additional uses of ultrasound simulation should be explored in the future. C1 [Bentley, Suzanne; Mudan, Gurpreet; Strother, Christopher] Icahn Sch Med Mt Sinai, Dept Emergency Med, New York, NY 10029 USA. [Bentley, Suzanne] Elmhurst Hosp Ctr, Dept Emergency Med, Elmhurst, NY USA. [Wong, Nelson] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Bentley, S (reprint author), 7901 Broadway, Elmhurst, NY 11373 USA. EM bentleys@nychhc.org NR 13 TC 1 Z9 1 U1 0 U2 1 PU WESTJEM PI ORANGE PA C/O SHAHRAM LOTFIPOUR, MD, MPH, 333 CITY BLVD W STE 640, RT 128-01, ORANGE, CA 92868 USA SN 1936-900X EI 1936-9018 J9 WEST J EMERG MED JI West. J. Emerg. Med. PD NOV PY 2015 VL 16 IS 6 SI SI BP 818 EP 822 DI 10.5811/westjem.2015.9.27276 PG 5 WC Emergency Medicine SC Emergency Medicine GA DH9OG UT WOS:000373124900005 PM 26594272 ER PT J AU LeBaron, VT Blonquist, TM Hong, FX Halpenny, B Berry, DL AF LeBaron, Virginia T. Blonquist, Traci M. Hong, Fangxin Halpenny, Barbara Berry, Donna L. TI Screening for Pain in the Ambulatory Cancer Setting: Is 0-10 Enough? SO JOURNAL OF ONCOLOGY PRACTICE LA English DT Article ID SELF-REPORT ASSESSMENT; ADVANCED-STAGE CANCER; OPTIMAL CUT POINTS; MODERATE; QUALITY; DISTRESS; MILD; VARIABILITY; PATIENT; CARE AB Purpose: The purpose of this study was to explore concordance between patient self-reports of pain on validated questionnaires and discussions of pain in the ambulatory oncology setting. Methods: Adult, ambulatory patients (N = 452) with all stages of cancer were included. Three pain measures were evaluated: two items from the Symptom Distress Scale (frequency [SDSF] and intensity [SDSI]) and the Pain Intensity Numeric Scale (PINS). Relevant pain was defined as: (1) scores 3 of 5 on SDSF or SDSI or 5 of 10 on the (PINS); or (2) discussion of existing pain in an audio-recorded clinic visit. For each scale, McNemar's test assessed concordance of patient self-reports of relevant pain with discussions of relevant pain in the audio-recorded clinic visit. Sensitivity, specificity, and accuracy were calculated and a receiver operating characteristic analysis evaluated thresholds on self-report pain questionnaires to best identify relevant pain discussed in clinic. Results: Identification of relevant pain by self-report was discordant (P < .001) with discussed pain coded in audio-recorded visits for all three measures. Specificity was higher for intensity (SDSI, 0.94; PINS, 0.97) than frequency (SDSF, 0.87); sensitivity was higher for frequency (SDSF, 0.35) than intensity (SDSI, 0.24; PINS, 0.12). Accuracy was higher for the SDS pain items (SDSF, 0.57; SDSI, 0.54) than for PINS (0.48). Receiver operating characteristic analysis curves suggest that lower threshold scores may improve the identification of relevant pain. Conclusion: Self-report pain screening measures favored specificity over sensitivity. Asking about pain frequency (in addition to intensity) and reconsidering threshold scores on pain intensity scales may be practical strategies to more accurately identify patients with cancer who have relevant pain. C1 [LeBaron, Virginia T.] Univ Virginia, Sch Nursing, McLeod Hall,202 Jeanette Lancaster Way, Charlottesville, VA 22903 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Phyllis Cantor Ctr Res Nursing & Patient Care Ser, Boston, MA 02115 USA. RP LeBaron, VT (reprint author), Univ Virginia, Sch Nursing, McLeod Hall,202 Jeanette Lancaster Way, Charlottesville, VA 22903 USA. EM vlebaron@virginia.edu FU NCI NIH HHS [U54 CA156732, U54CA156732]; NINR NIH HHS [R01 NR008726, R01NR008726-04] NR 38 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 1554-7477 EI 1935-469X J9 J ONCOL PRACT JI J. Oncol. Pract. PD NOV PY 2015 VL 11 IS 6 BP 435 EP + DI 10.1200/JOP.2015.004077 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DG5CS UT WOS:000372091100002 PM 26306620 ER PT J AU Choi, JW Kim, JK Yang, YJ Kim, P Yoon, KH Yun, SH AF Choi, Jin Woo Kim, Jun Ki Yang, Yun Jung Kim, Pilhan Yoon, Kwon-Ha Yun, Seok Hyun TI Urokinase Exerts Antimetastatic Effects by Dissociating Clusters of Circulating Tumor Cells SO CANCER RESEARCH LA English DT Article ID INDUCED PLATELET-AGGREGATION; EXPERIMENTAL METASTASIS; FIBRINOGEN INFLUX; CANCER METASTASIS; PERIPHERAL-BLOOD; BREAST-CANCER; SIZE; THROMBOSIS; SYSTEM; STROMA AB Clusters of circulating tumor cells (CTC) exhibit more robust metastatic properties than single CTC. Thus, understanding the distinct behaviors of CTC clusters and how CTC clustering is regulated may offer new insights into how to limit metastasis. In this study, we utilized an in vivo confocal system to observe the clustering behavior of CTC in real time, finding that the number of clusters increased proportionally with the growth of the primary tumor. Our experiments also indicated that the flow rate of the CTC clusters in blood vessels was relatively slower than single CTC due to increased vessel wall adhesion. Depending on disease stage, 5% to 10% of total CTC in circulation were in clusters, with this proportion increasing to >24% within lung metastases examined. Notably, in the 4T1 mouse model of breast cancer metastasis, we found that injecting host animals with urokinase-type plasminogen activator, a clinical thrombolytic agent, was effective at preventing the assembly of CTC clusters and prolonging overall host survival by approximately 20% relative to control animals. Our results suggest a tractable approach to limit metastasis by suppressing the formation or stability of CTC clusters circulating in the blood of cancer patients. (C) 2015 AACR. C1 [Choi, Jin Woo; Yang, Yun Jung] Wonkwang Univ, Sch Dent, Wonkwang Inst Integrat Biomed Sci, Iksan, Chonbuk, South Korea. [Choi, Jin Woo; Yang, Yun Jung] Wonkwang Univ, Sch Dent, Dent Res Ctr, Iksan, Chonbuk, South Korea. [Choi, Jin Woo; Yoon, Kwon-Ha] Wonkwang Univ, Imaging Sci Based Lung & Bone Dis Res Ctr, Iksan, Cheonbuk, South Korea. [Choi, Jin Woo] Seoul Natl Univ, Adv Inst Convergence Technol, Suwon, Gyenggi Do, South Korea. [Kim, Jun Ki] Asan Med Ctr, Asan Inst Life Sci, Ctr Biomed Engn, Seoul, South Korea. [Kim, Jun Ki] Univ Ulsan, Coll Med, Seoul, South Korea. [Kim, Pilhan] Korea Adv Inst Sci & Technol, Grad Sch Nanosci & Technol, Daejeon, South Korea. [Yoon, Kwon-Ha] Wonkwang Univ, Sch Med, Dept Radiol, Iksan, Jeonbuk, South Korea. [Yun, Seok Hyun] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02115 USA. RP Choi, JW (reprint author), Wonkwang Univ, Iksan 570711, Cheonbuk, South Korea. EM jinwoochoi@wku.ac.kr; khy1646@wku.ac.kr; syun@hms.harvard.edu RI Kim, Pilhan/C-1836-2011 OI Kim, Pilhan/0000-0001-8388-1840 FU National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning [2014R1A1A1002431, NRF-2013M3A6A4072626]; Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea [HI12C0110] FX This work was supported by Basic Science Research Program (2014R1A1A1002431) and Global Frontier Project grants (NRF-2013M3A6A4072626), through the National Research Foundation of Korea (NRF), and funded by the Ministry of Science, ICT & Future Planning. This work was also supported by a grant (HI12C0110) from Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea. NR 47 TC 4 Z9 4 U1 7 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2015 VL 75 IS 21 BP 4474 EP 4482 DI 10.1158/0008-5472.CAN-15-0684 PG 9 WC Oncology SC Oncology GA DE9LX UT WOS:000370960100001 PM 26527605 ER PT J AU Tsai, J Mota, NP Pietrzak, RH AF Tsai, Jack Mota, Natalie P. Pietrzak, Robert H. TI US Female Veterans Who Do and Do Not Rely on VA Health Care: Needs and Barriers to Mental Health Treatment SO PSYCHIATRIC SERVICES LA English DT Article ID WOMEN VETERANS; AFGHANISTAN VETERANS; ADMINISTRATION CARE; UNINSURED VETERANS; INSURANCE-COVERAGE; PERCEIVED STIGMA; NATIONAL-HEALTH; SAMPLE; IRAQ; PSYCHOTHERAPY AB Objectives: To determine mental health service utilization and barriers among female veterans, this study examined the prevalence of U.S. female veterans who identified the U.S. Department of Veterans Affairs (VA) as their main source of health care. Methods: This observational study used data from a nationally representative sample of 1,202 veterans who completed a Web-based survey. The analysis compared sociodemographic and clinical characteristics, mental health service use, and perceived barriers to mental health care among female veterans who do and do not use the VA as their main source of health care and male veterans who mainly use VA health care. Results: By gender, 23.4% of female veterans and 19.6% of male veterans identified the VA as their main source of health care, which was not significantly different. Compared with male VA patients, women were more likely to be single, younger, and from a racial-ethnic minority group and to screen positive for depression and posttraumatic stress disorder (PTSD), but they were less likely to have a substance use disorder. Compared with female veterans who did not mainly use VA care, female VA patients were more likely to be on a low income, not employed, from racial-ethnic minority groups, and combat veterans, and they were more likely to have a disability, to screen positive for PTSD, and to report poorer mental health-related functioning. There were no group differences in mental health service use, and the most frequently endorsed barriers to using mental health care across veteran groups were "high treatment costs" and "being seen as weak." Conclusions: These findings highlight the health care needs of female VA service users and support efforts to dispel misconceptions and stigma related to mental health care. C1 [Tsai, Jack] US Dept Vet Affairs, Dept Psychiat, Connecticut Healthcare Syst, West Haven, CT USA. [Tsai, Jack; Mota, Natalie P.; Pietrzak, Robert H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. RP Tsai, J (reprint author), US Dept Vet Affairs, Dept Psychiat, Connecticut Healthcare Syst, West Haven, CT USA. EM jack.tsai@yale.edu NR 44 TC 3 Z9 3 U1 3 U2 7 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 NOV PY 2015 VL 66 IS 11 BP 1200 EP 1206 DI 10.1176/appi.ps.201400550 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA DE7WD UT WOS:000370846500014 PM 26174948 ER PT J AU Vick, CW AF Vick, C. Whitley TI My first RSNA meeting: A wacky memoir SO APPLIED RADIOLOGY LA English DT Editorial Material C1 [Vick, C. Whitley] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Vick, C. Whitley] Yale Univ, Ultrasound, New Haven, CT 06520 USA. [Vick, C. Whitley] Virginia Commonwealth Univ Med Coll Virginia, Richmond, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ANDERSON PUBLISHING, INC PI SCOTCH PLAINS PA 180 GLENSIDE AVE, SCOTCH PLAINS, NJ 07076 USA SN 0160-9963 EI 1879-2898 J9 APPL RADIOL JI Appl. Radiol. PD NOV PY 2015 VL 44 IS 11 BP 6 EP + PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DE4QV UT WOS:000370615600001 ER PT J AU Kamalian, S Kamalian, S Boulter, DJ Lev, MH Gonzalez, RG Schaefer, PW AF Kamalian, Shahmir Kamalian, Shervin Boulter, Daniel J. Lev, Michael H. Gonzalez, R. Gilberto Schaefer, Pamela W. TI Stroke differential diagnosis and mimics: Part 1 SO APPLIED RADIOLOGY LA English DT Article ID DIFFUSION-WEIGHTED MR; CREUTZFELDT-JAKOB-DISEASE; TRANSIENT GLOBAL AMNESIA; PARTIAL STATUS EPILEPTICUS; HERPES-SIMPLEX-ENCEPHALITIS; OF-THE-LITERATURE; CENTRAL PONTINE MYELINOLYSIS; ACUTE HEPATIC-ENCEPHALOPATHY; CEREBRAL VENOUS THROMBOSIS; IMAGING FINDINGS C1 [Kamalian, Shahmir] Univ Massachusetts, Sch Med, Dept Radiol, Worcester, MA USA. [Kamalian, Shervin] Mt Auburn Hosp, Dept Radiol, Cambridge, MA 02238 USA. [Boulter, Daniel J.] Ohio State Univ, Dept Radiol, Columbus, OH 43210 USA. [Lev, Michael H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Emergency Imaging, Boston, MA USA. [Lev, Michael H.; Gonzalez, R. Gilberto; Schaefer, Pamela W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Radiol, Boston, MA USA. [Gonzalez, R. Gilberto; Schaefer, Pamela W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroradiol, Boston, MA USA. RP Kamalian, S (reprint author), Univ Massachusetts, Sch Med, Dept Radiol, Worcester, MA USA. NR 133 TC 0 Z9 0 U1 0 U2 0 PU ANDERSON PUBLISHING, INC PI SCOTCH PLAINS PA 180 GLENSIDE AVE, SCOTCH PLAINS, NJ 07076 USA SN 0160-9963 EI 1879-2898 J9 APPL RADIOL JI Appl. Radiol. PD NOV PY 2015 VL 44 IS 11 BP 26 EP + PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DE4QV UT WOS:000370615600003 ER PT J AU Kamalian, S Kamalian, S Boulter, DJ Lev, MH Gonzalez, RG Schaefer, PW AF Kamalian, Shahmir Kamalian, Shervin Boulter, Daniel J. Lev, Michael H. Gonzalez, R. Gilberto Schaefer, Pamela W. TI Stroke differential diagnosis and mimics: Part 2 SO APPLIED RADIOLOGY LA English DT Article ID CEREBRAL VASOCONSTRICTION SYNDROMES; REVERSIBLE ENCEPHALOPATHY SYNDROME; DIFFUSION-WEIGHTED MRI; AUTOSOMAL-DOMINANT ARTERIOPATHY; MARCHIAFAVA-BIGNAMI-DISEASE; FAT-EMBOLISM SYNDROME; MULTIPLE-SCLEROSIS; IMAGING FINDINGS; CORPUS-CALLOSUM; AXONAL INJURY C1 [Kamalian, Shahmir] Univ Massachusetts, Sch Med, Dept Radiol, Worcester, MA USA. [Kamalian, Shervin] Mt Auburn Hosp, Dept Radiol, Cambridge, MA 02238 USA. [Boulter, Daniel J.] Ohio State Univ, Dept Radiol, Columbus, OH 43210 USA. [Lev, Michael H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Emergency Imaging, Boston, MA USA. [Lev, Michael H.; Gonzalez, R. Gilberto; Schaefer, Pamela W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Radiol, Boston, MA USA. [Gonzalez, R. Gilberto; Schaefer, Pamela W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroradiol, Boston, MA USA. RP Kamalian, S (reprint author), Univ Massachusetts, Sch Med, Dept Radiol, Worcester, MA USA. NR 57 TC 0 Z9 0 U1 0 U2 0 PU ANDERSON PUBLISHING, INC PI SCOTCH PLAINS PA 180 GLENSIDE AVE, SCOTCH PLAINS, NJ 07076 USA SN 0160-9963 EI 1879-2898 J9 APPL RADIOL JI Appl. Radiol. PD NOV PY 2015 VL 44 IS 11 BP 39A EP 39I PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DE4QV UT WOS:000370615600005 ER PT J AU Mahesh, M Tanenbaum, LN Sahani, DV Hellinger, JC AF Mahesh, Mahadevappa Tanenbaum, Lawrence N. Sahani, Dushyant V. Hellinger, Jeffrey C. TI Enhancing Patient Safety in Today's Healthcare Environment: Radiation Dose and Contrast Optimization in CT Imaging SO APPLIED RADIOLOGY LA English DT Editorial Material ID HIGH-IODINE; PERFUSION; QUALITY; BRAIN C1 [Mahesh, Mahadevappa] Johns Hopkins Med, Radiol & Radiol Sci, Baltimore, MD USA. [Tanenbaum, Lawrence N.] RadNet Inc, East Reg, Los Angeles, CA USA. [Tanenbaum, Lawrence N.] RadNet Inc, CT MR & Adv Imaging, Los Angeles, CA USA. [Sahani, Dushyant V.] Massachusetts Gen Hosp, Radiol, Boston, MA 02114 USA. [Sahani, Dushyant V.] Massachusetts Gen Hosp, Comp Tomog, Boston, MA 02114 USA. [Hellinger, Jeffrey C.] Lenox Hill Radiol & Med Imaging Associates, New York, NY USA. RP Mahesh, M (reprint author), Johns Hopkins Med, Radiol & Radiol Sci, Baltimore, MD USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU ANDERSON PUBLISHING, INC PI SCOTCH PLAINS PA 180 GLENSIDE AVE, SCOTCH PLAINS, NJ 07076 USA SN 0160-9963 EI 1879-2898 J9 APPL RADIOL JI Appl. Radiol. PD NOV PY 2015 VL 44 IS 11 BP 56 EP 60 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DE4QV UT WOS:000370615600009 ER PT J AU Bassett, IV Wilson, D Taaffe, J Freedberg, KA AF Bassett, Ingrid V. Wilson, David Taaffe, Jessica Freedberg, Kenneth A. TI Financial incentives to improve progression through the HIV treatment cascade SO CURRENT OPINION IN HIV AND AIDS LA English DT Review DE financial incentives; HIV care cascade; HIV prevention ID CONDITIONAL ECONOMIC INCENTIVES; CLUSTER RANDOMIZED-TRIAL; CASH TRANSFERS; SOUTH-AFRICA; SMOKING-CESSATION; ADHERENCE; CARE; RISK; PROGRAM; INTERVENTIONS AB Purpose of review We reviewed recent literature on conditional and unconditional financial incentives for their impact on improving movement through the HIV care cascade and HIV prevention. Recent findings Concepts from behavioral economics may help improve engagement in HIV care by addressing upstream structural risk factors for HIV, such as poverty, or providing conditional rewards for immediate, measurable outcomes related to HIV care. Incentives have been shown to increase uptake of HIV testing. Yet, few studies to date focus on linkage to care: one large USA-based randomized trial failed to show an effect of incentives; and a smaller trial showed improved linkage to care among drug users, but no difference in virologic suppression. Several small USA-based studies have shown an impact of financial incentives on antiretroviral therapy adherence, but without durability beyond the incentive period. HIV prevention has the most robust evidence for decreasing HIV risk-taking behavior among adolescents and may serve as a model for research on the care cascade. Summary Financial incentives show promise for improving engagement in HIV testing, care, and prevention. Understanding the durability, scalability, ease of implementation, and cost-effectiveness of these different approaches will be critical for maximizing the impact of incentives in curtailing the HIV epidemic. C1 [Bassett, Ingrid V.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, 50 Staniford St, Boston, MA 02140 USA. [Bassett, Ingrid V.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02140 USA. [Bassett, Ingrid V.; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02140 USA. [Bassett, Ingrid V.; Freedberg, Kenneth A.] Harvard Univ, Harvard Ctr AIDS Res, Boston, MA 02115 USA. [Wilson, David; Taaffe, Jessica] World Bank, Global AIDS Program, 1818 H St NW, Washington, DC 20433 USA. [Freedberg, Kenneth A.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Bassett, IV (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 50 Staniford St, Boston, MA 02140 USA. EM ibassett@partners.org FU National Institutes of Health [R21 AI110264, R01AI058736] FX This work was supported by the National Institutes of Health: R21 AI110264 and R01AI058736. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 37 TC 8 Z9 8 U1 4 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1746-630X EI 1746-6318 J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD NOV PY 2015 VL 10 IS 6 BP 451 EP 463 DI 10.1097/COH.0000000000000196 PG 13 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA DD1YI UT WOS:000369718800009 PM 26371461 ER PT J AU Bor, J Geldsetzer, P Venkataramani, A Barnighausen, T AF Bor, Jacob Geldsetzer, Pascal Venkataramani, Atheendar Baernighausen, Till TI Quasi-experiments to establish causal effects of HIV care and treatment and to improve the cascade of care SO CURRENT OPINION IN HIV AND AIDS LA English DT Review DE cascade of care; causal inference; HIV/AIDS; natural experiment; quasi-experiment ID REGRESSION DISCONTINUITY DESIGNS; ANTIRETROVIRAL THERAPY; NATURAL EXPERIMENT; SOUTH-AFRICA; ARV TREATMENT; SCALE-UP; IMPACT; MORTALITY; KENYA; AIDS AB Purpose of review Randomized, population-representative trials of clinical interventions are rare. Quasi-experiments have been used successfully to generate causal evidence on the cascade of HIV care in a broad range of real-world settings. Recent findings Quasi-experiments exploit exogenous, or quasi-random, variation occurring naturally in the world or because of an administrative rule or policy change to estimate causal effects. Well designed quasi-experiments have greater internal validity than typical observational research designs. At the same time, quasi-experiments may also have potential for greater external validity than experiments and can be implemented when randomized clinical trials are infeasible or unethical. Quasi-experimental studies have established the causal effects of HIV testing and initiation of antiretroviral therapy on health, economic outcomes and sexual behaviors, as well as indirect effects on other community members. Recent quasi-experiments have evaluated specific interventions to improve patient performance in the cascade of care, providing causal evidence to optimize clinical management of HIV. Summary Quasi-experiments have generated important data on the real-world impacts of HIV testing and treatment and on interventions to improve the cascade of care. With the growth in large-scale clinical and administrative data, quasi-experiments enable rigorous evaluation of policies implemented in real-world settings. C1 [Bor, Jacob] Boston Univ, Sch Publ Hlth, Dept Global Hlth, Boston, MA USA. [Bor, Jacob] Univ Witwatersrand, Hlth Econ & Epidemiol Res Off, Johannesburg, South Africa. [Geldsetzer, Pascal; Baernighausen, Till] Harvard Univ, TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. [Venkataramani, Atheendar] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Baernighausen, Till] Africa Ctr Hlth & Populat Studies, Mtubatuba, South Africa. RP Bor, J (reprint author), 801 Massachusetts Ave,3rd Floor, Boston, MA 02118 USA. EM jbor@bu.edu FU National Institutes of Health [1K01MH105320-01A1] FX This work was supported in part by National Institutes of Health grant 1K01MH105320-01A1 (J.B.). NR 60 TC 2 Z9 2 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1746-630X EI 1746-6318 J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD NOV PY 2015 VL 10 IS 6 BP 495 EP 501 DI 10.1097/COH.0000000000000191 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA DD1YI UT WOS:000369718800014 PM 26371463 ER PT J AU Adler, AR Charnin, JA Quraishi, SA AF Adler, Alexandra R. Charnin, Jonathan A. Quraishi, Sadeq A. TI Serotonin Syndrome: The Potential for a Severe Reaction Between Common Perioperative Medications and Selective Serotonin Reuptake Inhibitors SO A & A CASE REPORTS LA English DT Article ID METHYLENE-BLUE; TOXICITY; PARATHYROIDECTOMY; PERIOD AB Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed to patients of all ages. Although generally considered safe, therapy with SSRIs can be complicated by serotonin syndrome (SS), a life-threatening condition. We present a case of SS that developed in a young man who was receiving a stable dose of fluoxetine and then received several commonly used medications during an emergent appendectomy. Because polypharmacy in the perioperative setting may trigger SS, it is important for anesthesiologists to be cognizant of the interactions between SSRIs and common perioperative medications to formulate anesthetic plans that optimize patient safety. C1 [Adler, Alexandra R.] Cambridge Hlth Alliance, Dept Med, 1493 Cambridge St, Cambridge, MA 02139 USA. [Charnin, Jonathan A.; Quraishi, Sadeq A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Charnin, Jonathan A.; Quraishi, Sadeq A.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. RP Adler, AR (reprint author), Cambridge Hlth Alliance, Dept Med, 1493 Cambridge St, Cambridge, MA 02139 USA. EM aliradler@gmail.com NR 27 TC 1 Z9 1 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2325-7237 J9 A A CASE REP JI A A Case Rep. PD NOV 1 PY 2015 VL 5 IS 9 BP 156 EP 159 DI 10.1213/XAA.0000000000000217 PG 4 WC Anesthesiology SC Anesthesiology GA DC7SR UT WOS:000369421200003 PM 26528701 ER PT J AU William, JH Gilbert, AL Rosas, SE AF William, Jeffrey H. Gilbert, Aubrey L. Rosas, Sylvia E. TI Keeping an eye on dialysis: the association of hemodialysis with intraocular hypertension SO CLINICAL NEPHROLOGY LA English DT Article DE hemodialysis; disequilibrium; ocular ophthalmology ID OCULAR PERFUSION; PRESSURE; PREVENTION; ELEVATION; GLAUCOMA; GLUCOSE; PATIENT AB Intraocular hypertension is common during hemodialysis. Dialysis disequilibrium syndrome and intraocular hypertension occur via similar pathophysiologic mechanisms. These mechanisms may contribute to the development of glaucoma and cataracts in a patient population already at high risk for ocular abnormalities, given the common risk factors for chronic kidney disease and impaired aqueous humor outflow. We describe a patient with complicated diabetes mellitus, end-stage renal disease, and recent cataract surgery who developed severe intraocular hypertension during hemodialysis. We recommend increased awareness of the symptoms of intraocular hypertension and subsequent ophthalmologic surveillance in order to prevent long-term visual complications. C1 [William, Jeffrey H.; Rosas, Sylvia E.] Beth Israel Deaconess Med Ctr, Div Nephrol, Boston, MA 02215 USA. [Gilbert, Aubrey L.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Rosas, Sylvia E.] Joslin Diabet Ctr, Kidney & Hypertens Sect, Boston, MA 02215 USA. RP William, JH (reprint author), 185 Pilgrim Rd,Farr 8, Boston, MA 02215 USA. EM jhwillia@bidmc.harvard.edu NR 19 TC 0 Z9 1 U1 1 U2 4 PU DUSTRI-VERLAG DR KARL FEISTLE PI DEISENHOFEN-MUENCHEN PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD NOV PY 2015 VL 84 IS 5 BP 307 EP 310 DI 10.5414/CN108477 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA DC5FT UT WOS:000369247600009 PM 26042412 ER PT J AU Nigwekar, SU AF Nigwekar, Sagar U. TI Multidisciplinary approach to calcific uremic arteriolopathy SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review DE calcific uremic arteriolopathy; calciphylaxis; sodium thiosulfate; vitamin K ID STAGE RENAL-DISEASE; SODIUM THIOSULFATE THERAPY; HYPERBARIC-OXYGEN THERAPY; CASE SERIES; VASCULAR CALCIFICATION; HEMODIALYSIS-PATIENT; CUTANEOUS CALCIPHYLAXIS; SYSTEMIC CALCIPHYLAXIS; SKIN NECROSIS; RISK-FACTORS AB Purpose of review Calcific uremic arteriolopathy (CUA), as known as calciphylaxis, is a rare and poorly understood disease seen predominantly in end stage renal disease patients. A collaborative multidisciplinary approach to develop and implement treatment and prevention methods is described. Recent findings Overall, the scientific literature on CUA is largely restricted to case reports and case series. Recent reports indicate that the incidence of CUA may be on the rise and emphasize an association with vitamin K antagonist therapy, obesity, and diabetes mellitus. Serum calcium, phosphorous, and parathyroid hormone levels have been reported to be quite variable in patients with CUA and may reflect the heterogeneity of study designs. A multidisciplinary and multimodal approach that incorporates wound and pain management, sodium thiosulfate, optimization of mineral bone parameters, bisphosphonates, and avoidance of risk factors such as vitamin K antagonist has been advocated in the latest reports. Sodium thiosulfate although used frequently to treat CUA has unclear efficacy requiring further examination. Summary This review describes the recent literature in the field of CUA including its limitations. It provides a summary of a multidisciplinary approach to CUA management. C1 [Nigwekar, Sagar U.] Massachusetts Gen Hosp, Div Nephrol, Dept Med, Boston, MA 02114 USA. RP Nigwekar, SU (reprint author), 165 Cambridge St,Suite 302, Boston, MA 02114 USA. EM snigwekar@mgh.harvard.edu FU National Kidney Foundation's Young Investigator Award; Fund for Medical Discovery Award from the Massachusetts General Hospital's Executive Committee on Research [R00000000007190]; American Heart Association's NCRP Summer Mentored Clinical and Population Research Award [15CRP22900008]; American Heart Association's NCRP Winter Fellow-to-Faculty Transition Award [15FTF25980003] FX S.U.N. is supported by the National Kidney Foundation's Young Investigator Award, the Fund for Medical Discovery Award from the Massachusetts General Hospital's Executive Committee on Research (R00000000007190), the American Heart Association's NCRP Summer 2014 Mentored Clinical and Population Research Award (15CRP22900008), and by the American Heart Association's NCRP Winter 2015 Fellow-to-Faculty Transition Award (15FTF25980003). NR 89 TC 5 Z9 5 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1062-4821 EI 1473-6543 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD NOV PY 2015 VL 24 IS 6 BP 531 EP 537 DI 10.1097/MNH.0000000000000175 PG 7 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA DD0MH UT WOS:000369613600010 PM 26371529 ER PT J AU Vodopivec, I Matiello, M Prasad, S AF Vodopivec, Ivana Matiello, Marcelo Prasad, Sashank TI Treatment of neuromyelitis optica SO CURRENT OPINION IN OPHTHALMOLOGY LA English DT Review DE antiaquaporin-4 antibodies; myelitis; neuromyelitis optica; optic neuritis; treatment ID EXTENSIVE TRANSVERSE MYELITIS; MULTIPLE-SCLEROSIS; SPECTRUM DISORDER; PLASMA-EXCHANGE; AQUAPORIN 4; RETROSPECTIVE ANALYSIS; THERAPEUTIC APHERESIS; RHEUMATOID-ARTHRITIS; CLINICAL PREDICTORS; NATALIZUMAB THERAPY AB Purpose of review Neuromyelitis optica (NMO) is an antibody-mediated inflammatory disease of the central nervous system with a predilection for the optic nerves, spinal cord and certain brain regions. It has a distinct pathogenesis relating to aquaporin-4 autoimmunity and complement-mediated injury. This knowledge has translated into targeted efforts to develop novel, disease-specific treatments. In this review, we discuss evidence supporting the use of currently available treatments for acute exacerbations and for long-term disease modification. We also discuss the risks and benefits of available and emerging immunotherapies. Recent findings Early, accurate diagnosis of NMO with appropriate acute and long-term immunosuppressive treatment is of prime importance for the prevention of disability associated with this disease. Standard measures for the management of acute exacerbations include intravenous methylprednisolone and plasmapheresis. First-line, long-term immunotherapies for NMO include azathioprine, mycophenolate mofetil and rituximab. Three randomized controlled treatment trials evaluating these agents are currently being conducted. In addition, there are numerous emerging therapies that are based upon current understanding of the disease immunopathogenesis. Summary NMO is an autoimmune disease that is separate from multiple sclerosis. Better understanding of its antibody and complement-dependent pathophysiology has proven to be critical for the formulation of current and future treatment strategies. C1 [Vodopivec, Ivana; Matiello, Marcelo; Prasad, Sashank] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Vodopivec, Ivana; Matiello, Marcelo] Massachusetts Gen Hosp, Dept Neurol, 15 Parkman St, Boston, MA 02114 USA. [Matiello, Marcelo; Prasad, Sashank] Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. RP Vodopivec, I (reprint author), Massachusetts Gen Hosp, Dept Neurol, 15 Parkman St, Boston, MA 02114 USA. EM ivodopivec@partners.org NR 92 TC 2 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-8738 EI 1531-7021 J9 CURR OPIN OPHTHALMOL JI Curr. Opin. Ophthalmol. PD NOV PY 2015 VL 26 IS 6 BP 476 EP 483 DI 10.1097/ICU.0000000000000202 PG 8 WC Ophthalmology SC Ophthalmology GA DD0HA UT WOS:000369599800007 PM 26367088 ER PT J AU Rao, R MacIntosh, PW Yoon, MK Lefebvre, DR AF Rao, Rohini MacIntosh, Peter W. Yoon, Michael K. Lefebvre, Daniel R. TI Current trends in the management of thyroid eye disease SO CURRENT OPINION IN OPHTHALMOLOGY LA English DT Review DE dysthyroid optic neuropathy; orbital decompression; orbital radiation therapy; thyroid eye disease ID ENDOSCOPIC ORBITAL DECOMPRESSION; COMPRESSIVE OPTIC NEUROPATHY; SEVERE GRAVES ORBITOPATHY; CONTROLLED-TRIAL; STEROID-THERAPY; OPHTHALMOPATHY; RITUXIMAB; RETRACTION; EFFICACY; SAFETY AB Purpose of review The present review summarizes the body of literature concerning the medical and surgical treatment of thyroid eye disease (TED) from 1 January 2014 through 30 March 2015. Recent findings Corticosteroids continue to be the primary medical therapy for TED. Recent research has offered insight into potential differences between oral corticosteroid and intravenous corticosteroid treatment regimens in terms of efficacy and side-effect profiles. Steroid-sparing medications, for example, rituximab and others, are an area of active study. There has been renewed interest in the role of radiation therapy as a nonmedical treatment for TED with some promising data. The use of balanced orbital decompression techniques have become popular, although the data regarding postoperative diplopia are mixed, and ` fat decompression' offers an alternative or an augmentation to bony decompression. Stereotactic image guidance is a useful adjunct to orbital decompression surgery. Summary TED continues to be a difficult condition for the patient to cope with and for the clinician to treat, and recent research builds on the present foundation of knowledge and treatments, but unfortunately does not offer paradigm-shifting information at the present time. C1 [Rao, Rohini; MacIntosh, Peter W.; Yoon, Michael K.; Lefebvre, Daniel R.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. [MacIntosh, Peter W.; Yoon, Michael K.; Lefebvre, Daniel R.] Massachusetts Eye & Ear Infirm, Ophthalm Plast Surg, Boston, MA 02114 USA. RP Lefebvre, DR (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM daniel_lefebvre@meei.harvard.edu NR 52 TC 4 Z9 4 U1 4 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-8738 EI 1531-7021 J9 CURR OPIN OPHTHALMOL JI Curr. Opin. Ophthalmol. PD NOV PY 2015 VL 26 IS 6 BP 484 EP 490 DI 10.1097/ICU.0000000000000203 PG 7 WC Ophthalmology SC Ophthalmology GA DD0HA UT WOS:000369599800008 PM 26397888 ER PT J AU Glass, LRD Freitag, SK AF Glass, Lora R. Dagi Freitag, Suzanne K. TI Management of orbital IgG4-related disease SO CURRENT OPINION IN OPHTHALMOLOGY LA English DT Review DE corticosteroid; orbital IgG4-related disease; radiation therapy; rituximab ID AUTOIMMUNE PANCREATITIS; INFLAMMATORY DISEASE; SYSTEMIC-DISEASE; INVOLVEMENT; DACRYOADENITIS; EXPERIENCE; RITUXIMAB; MYOSITIS; JAPAN AB Purpose of review IgG4-related disease (IgG4-RD) is a systemic process that can cause significant orbital disease. It can affect both sexes and all ages, with irreversible consequences if left untreated. Diagnosis is currently based upon a combination of clinical and imaging evidence of tissue swelling or mass, serum evidence of elevated IgG4 levels and histopathologic evidence of inappropriate IgG4 presence. The cause of IgG4-RD is as of yet unclear; this lack of understanding and the dearth of prospective studies have limited our ability to manage patients effectively. In this review, we discuss the most recent published evidence regarding best-practice management of IgG4-related orbital disease. Recent findings Recent literature remains retrospective, and has focused on the use of corticosteroid therapy as a first-line treatment. Rituximab infusions have also received significant attention, among other second-line agents. Radiation therapy has been reported to be effective. Long-term monitoring for relapse, involvement of other organ systems and potential neoplastic transformation is required. Summary The management of orbital IgG4-RD will gain from more targeted therapy in the future as the underlying cause is better understood. In the meantime, randomized, controlled trials of varying treatment regimens would be of benefit. C1 [Glass, Lora R. Dagi; Freitag, Suzanne K.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ophthalm Plast Surg Serv, Boston, MA 02115 USA. RP Freitag, SK (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM eyelid@meei.harvard.edu NR 36 TC 4 Z9 4 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-8738 EI 1531-7021 J9 CURR OPIN OPHTHALMOL JI Curr. Opin. Ophthalmol. PD NOV PY 2015 VL 26 IS 6 BP 491 EP 497 DI 10.1097/ICU.0000000000000204 PG 7 WC Ophthalmology SC Ophthalmology GA DD0HA UT WOS:000369599800009 PM 26367090 ER PT J AU Martires, J Zeidler, M AF Martires, Joanne Zeidler, Michelle TI The value of mindfulness meditation in the treatment of insomnia SO CURRENT OPINION IN PULMONARY MEDICINE LA English DT Review DE cognitive behavioral therapy for insomnia (CBT-I); insomnia; mindfulness-based stress reduction (MBSR); mindfulness-based therapy for insomnia (MBTI) ID RANDOMIZED CONTROLLED-TRIAL; COGNITIVE-BEHAVIORAL THERAPY; STRESS REDUCTION; BREAST-CANCER; ANXIETY DISORDERS; CLINICAL-TRIAL; SLEEP DISTURBANCE; OLDER-ADULTS; QUALITY; PHARMACOTHERAPY AB Purpose of review Insomnia is the most common reported sleep disorder with limited treatment options including pharmacotherapy and cognitive behavioral therapy for insomnia. Pharmacotherapy can be complicated by tolerance and significant side-effects and cognitive behavioral therapy for insomnia providers are limited in number. This article reviews mindfulness meditation as an additional therapy for insomnia. Recent findings Both mindfulness-based stress reduction (MBSR) and mindfulness-based therapy for insomnia (MBTI) have been studied in the treatment of insomnia. Randomized controlled studies of MBSR and MBTI have shown overall reduction in sleep latency and total wake time and increase in total sleep time after mindfulness therapy using both patient reported outcome and quantitative measures of sleep. Mindfulness techniques have been shown to be well accepted by patients with long-lasting effects. A three-arm randomized study with MBSR, MBTI, and self-monitoring showed similar improvement in insomnia between the MBSR and MBTI groups, with possibly longer duration of efficacy in the MBTI group. Recent data show that MBTI is also an effective and accepted treatment for insomnia in older patients. Summary Increasing evidence shows that mindfulness meditation, delivered either via MBSR or MBTI, can be successfully used for the treatment of insomnia with good patient acceptance and durable results. C1 [Martires, Joanne; Zeidler, Michelle] Greater Angeles VA Healthcare Syst, Los Angeles, CA USA. RP Zeidler, M (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Greater Los Angeles VA Healthcare Syst, 11301 Wilshire Blvd,111Q, Los Angeles, CA 90073 USA. EM mzeidler@mednet.ucla.edu NR 40 TC 1 Z9 1 U1 15 U2 64 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1070-5287 EI 1531-6971 J9 CURR OPIN PULM MED JI Curr. Opin. Pulm. Med. PD NOV PY 2015 VL 21 IS 6 BP 547 EP 552 DI 10.1097/MCP.0000000000000207 PG 6 WC Respiratory System SC Respiratory System GA DC5GG UT WOS:000369248900001 PM 26390335 ER PT J AU Elson, L Dounchis, J Illgen, R Marchand, RC Padgett, DE Bragdon, CR Malchau, H AF Elson, Leah Dounchis, Jon Illgen, Richard Marchand, Robert C. Padgett, Douglas E. Bragdon, Charles R. Malchau, Henrik TI Precision of acetabular cup placement in robotic integrated total hip arthroplasty SO HIP INTERNATIONAL LA English DT Article DE Arthroplasty; Hip; Acetabular cup positioning; Robotic-arm ID COMPONENT POSITION; DISLOCATION; VOLUME; NAVIGATION; THA AB Aims: The aim of this study was to assess the efficacy of stereotactic-arm assisted acetabular component placement during total hip arthroplasty (THA). Methods: 120 patients underwent primary THA at 4 different medical centres. A preoperative pelvic CT protocol was used to plan socket placement followed by robotic-arm assisted acetabular preparation and cup insertion. Intraoperative cup position was recorded and postoperative placement measured using Martell suite analysis software. Results: Using a 95% predictive intervals, robotic-arm cup placement was within +/-4 degrees of planned position in 95% of cases. Applying these data to the so-called safe zone, 96% of sockets were within the defined safe zone. Our data confirms that intraoperative robotic assistance improves the precision of preparation and position of the acetabular cup during total hip arthroplasty. C1 [Elson, Leah; Bragdon, Charles R.; Malchau, Henrik] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. [Dounchis, Jon] Creekside Med Ctr, Naples, FL USA. [Illgen, Richard] Univ Wisconsin, Madison, WI USA. [Marchand, Robert C.] South Cty Hosp, Wakefield, RI USA. [Padgett, Douglas E.] Hosp Special Surg, 535 E 70th St, New York, NY 10021 USA. RP Bragdon, CR (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRJ 1122, Boston, MA 02114 USA. EM cbragdon@partners.org FU MAKO Surgical Inc, Fort Lauderdale FL, USA FX Funding for this study was provided by MAKO Surgical Inc, Fort Lauderdale FL, USA. NR 20 TC 1 Z9 1 U1 1 U2 1 PU WICHTIG PUBL PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 1120-7000 EI 1724-6067 J9 HIP INT JI Hip Int. PD NOV-DEC PY 2015 VL 25 IS 6 BP 531 EP 536 DI 10.5301/hipint.5000289 PG 6 WC Orthopedics SC Orthopedics GA DC9GN UT WOS:000369529300006 PM 26391264 ER PT J AU Stone, GS Aruasa, W Tarus, T Shikanga, M Biwott, B Ngetich, T Andale, T Cheriro, B AF Stone, Geren S. Aruasa, Wilson Tarus, Titus Shikanga, Mainard Biwott, Benson Ngetich, Thomas Andale, Thomas Cheriro, Betsy TI The relationship of weekend admission and mortality on the public medical wards at a Kenyan referral hospital SO INTERNATIONAL HEALTH LA English DT Article DE Africa; Health services; Hospital admissions; Hospital medicine ID WEEKDAY ADMISSION AB Background: Research has demonstrated disparities in the outcomes of patients admitted to hospital on weekends in high-income countries. No published research has evaluated if any similar discrepancy exists in low-resource settings. Methods: To determine if any difference in mortality exists between weekend and weekday admissions on the public medical wards at a Kenyan referral hospital, we performed a retrospective observational study of inpatients over a 3-month study period. Results: During the study period, 261 (27.3%) of the 956 patients were admitted over the weekend. The mortality rates for patients admitted on weekends and weekdays did not differ with 156 (22.4%) of the 695 patients admitted on weekdays dying compared to 55 (21.1%) of the 261 patients admitted on weekends. After adjusting for age, insurance status, co-morbid illness, HIV status, employment, referral status and gender, still no association existed between weekend admission and mortality. Conclusions: Among adult patients on the medical wards, patients admitted on weekends had similar mortality rates to those admitted on weekdays. This similarity may reflect a stable level of care or a generalized shortage of resources and staffing that subsumes any impact of weekly variations. Future research examining optimal staffing and resource levels is needed in such settings. C1 [Stone, Geren S.] Massachusetts Gen Hosp, Dept Med, Ctr Global Hlth, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. [Stone, Geren S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Stone, Geren S.] Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA. [Stone, Geren S.] Moi Univ, Coll Hlth Sci, Sch Med, Dept Med, Eldoret 030100, Kenya. [Aruasa, Wilson; Tarus, Titus; Shikanga, Mainard; Biwott, Benson; Ngetich, Thomas; Andale, Thomas; Cheriro, Betsy] Moi Teaching & Referral Hosp, Eldoret 030100, Kenya. RP Stone, GS (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, 100 Cambridge St,15th Floor, Boston, MA 02114 USA. EM gstone@partners.org NR 17 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1876-3413 EI 1876-3405 J9 INT HEALTH JI Int. Health PD NOV PY 2015 VL 7 IS 6 BP 433 EP 437 DI 10.1093/inthealth/ihu100 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DC7AI UT WOS:000369370300011 PM 25602084 ER PT J AU Reddy, AT Andersen, RM Gelberg, L AF Reddy, Anjani T. Andersen, Ronald M. Gelberg, Lillian TI Clinicians' Beliefs and Practices Regarding Drug Use Care of Their Community Health Center Patients SO JOURNAL OF ADDICTION MEDICINE LA English DT Article DE clinicians; drug use; intervention; screening ID BRIEF INTERVENTION; NATIONAL-SURVEY; ILLICIT DRUG; ALCOHOL-USE; TRIAL; SETTINGS; PHYSICIANS; DISORDERS AB Objectives: Integration of behavioral health including substance use problems into primary care is an essential benefit that federally qualified health centers (FQHCs) will offer as part of the Affordable Care Act. This study explores FQHC primary care clinicians' beliefs and practices regarding illicit drug use assessment and treatment. Methods: We administered a 10-minute questionnaire to 68 primary care clinicians of 5 FQHCs in Los Angeles. Results: Clinicians expressed limited confidence in their ability to address patients' illicit drug use, scoring on average 3.31 on a 5-point Likert scale. Two thirds reported that they assess for drug use routinely "at every visit'' and/or "at annual visits.'' When asked how often they counsel regarding drug use (on a 5-point Likert scale from "never'' to "always''), the median response was 4 ("usually''). Regarding their perspectives on the best practical resource for addressing drug use in their clinics, 45.6% named primary care clinicians. A minority (29.4%) of clinicians had completed a clinical rotation dealing with substance use, and 27.2% reported receiving more than 10 hours of training regarding substance use problems. Having a substance use rotation was associated with greater confidence in drug use assessment and treatment (P < 0.01). More hours of substance use training was associated with greater confidence (P = 0.01) and routinely addressing substance use in their patients (P = 0.04). Conclusions: Although two thirds of the surveyed clinicians assess for drug use routinely, and on average, report that they usually address drug use, clinicians' confidence in substance use care seems to be suboptimal, but both confidence and routinely addressing substance use are associated with increased substance use education. Improving clinicians' training and integrating drug use care in FQHCs may improve confidence in substance use care and facilitate the Affordable Care Act's mandate to integrate behavioral health into routine FQHC primary care. C1 [Reddy, Anjani T.; Gelberg, Lillian] Univ Calif Los Angeles, Dept Family Med, David Geffen Sch Med, Los Angeles, CA 90024 USA. [Reddy, Anjani T.; Gelberg, Lillian] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Reddy, Anjani T.; Gelberg, Lillian] Vet Affairs Greater Los Angeles Healthcare Syst, Bldg 402,11301 Wilshire Ave, Los Angeles, CA 90037 USA. [Andersen, Ronald M.] Univ Calif Los Angeles, Dept Hlth Policy & Management, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Andersen, Ronald M.] Univ Calif Los Angeles, Dept Sociol, Los Angeles, CA 90024 USA. RP Reddy, AT (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Bldg 402,11301 Wilshire Ave, Los Angeles, CA 90037 USA. EM areddy@mednet.ucla.edu FU National Research Service Award Fellowship; NIDA [R01DA022445] FX Dr Reddy's work was supported by her National Research Service Award Fellowship. The NIDA Grant R01DA022445 funded the larger study, Quit Using Drugs Intervention Trial, that this work was part of. NR 20 TC 1 Z9 1 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1932-0620 EI 1935-3227 J9 J ADDICT MED JI J. Addict. Med. PD NOV-DEC PY 2015 VL 9 IS 6 BP 447 EP 453 DI 10.1097/ADM.0000000000000158 PG 7 WC Substance Abuse SC Substance Abuse GA DC9CR UT WOS:000369519000005 PM 26441402 ER PT J AU Gordon, AJ Lo-Ciganic, WH Cochran, G Gellad, WF Cathers, T Kelley, D Donohue, JM AF Gordon, Adam J. Lo-Ciganic, Wei-Hsuan Cochran, Gerald Gellad, Walid F. Cathers, Terri Kelley, David Donohue, Julie M. TI Patterns and Quality of Buprenorphine Opioid Agonist Treatment in a Large Medicaid Program SO JOURNAL OF ADDICTION MEDICINE LA English DT Article DE buprenorphine; health services; Medicaid; opioid-related disorders; opioid substitution treatment ID OFFICE-BASED TREATMENT; SUBSTANCE USE DISORDERS; DEPENDENCE; NALOXONE; PREVALENCE; METHADONE; TRENDS; PHYSICIANS; ADDICTION; DIVERSION AB Objectives: Use of buprenorphine - an effective treatment for opioid use disorders (OUDs) - has increased rapidly in recent years and is often financed by Medicaid. We investigated predictors of buprenorphine treatment, patterns of care, and quality of care in a large state Medicaid program. Methods: Data from Pennsylvania Medicaid from 2007 to 2012 provided information regarding diagnoses, demographic characteristics, enrollment, and use of inpatient and outpatient services, and prescription drugs. We identified adult enrollees using buprenorphine, and examined prevalence of OUD diagnosis and patterns of use (duration and dose) and quality of care (physician visits, receipt of behavioral health counseling, urine drug screens, and other prescription drug use). We use a mixed logistic regression model to examine enrollee characteristics associated with buprenorphine use. Results: The share of enrollees with OUD filling prescriptions for buprenorphine increased from 2985 (9.8%) to 12,691 (25.2%) from 2007 to 2012. Between 26.2 and 32.0% of enrollees using buprenorphine had no diagnosis of OUD, depending on the year. Only 60.1% of enrollees with buprenorphine use received at least one urine drug screen, 41.0% had behavioral health counseling services, and 34.7 and 38.0% had other opioid and benzodiazepine claims, respectively, concomitant with buprenorphine use. Quality of care was lower among those with no OUD diagnosis recorded. The mean daily doses of buprenorphine decreased over time. We found wide variation in likelihood of buprenorphine use among those with OUD based upon age, sex, and race. Conclusions: Increases in buprenorphine treatment in a Medicaid population were observed across time; however, increases varied by age, sex, and rate, and the quality of care received seemed to be generally poor. The quality of the provision of buprenorphine treatment occurring in Medicaid populations should be further explored. C1 [Gordon, Adam J.; Cochran, Gerald; Gellad, Walid F.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15240 USA. [Gordon, Adam J.; Gellad, Walid F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Gordon, Adam J.; Lo-Ciganic, Wei-Hsuan; Cochran, Gerald; Gellad, Walid F.; Donohue, Julie M.] Univ Pittsburgh, Ctr Pharmaceut Policy & Prescribing, Pittsburgh, PA 15240 USA. [Donohue, Julie M.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA 15240 USA. [Lo-Ciganic, Wei-Hsuan] Univ Arizona, Coll Pharm, Tucson, AZ 85721 USA. [Cochran, Gerald] Univ Pittsburgh, Sch Social Work, Pittsburgh, PA 15260 USA. [Cathers, Terri; Kelley, David] Penn Dept Human Serv, Philadelphia, PA USA. RP Gordon, AJ (reprint author), Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Bldg 30 151-C,Room 2a133,Univ Dr C, Pittsburgh, PA 15240 USA. EM adam.gordon@va.gov OI Donohue, Julie/0000-0003-2418-6017 FU Pennsylvania Department of Human Services; University of Pittsburgh; NIH, CDC [U01-CE002496]; VA; VA HSR&D Career Development Award [09-207] FX This work was supported in part by an intergovernmental agreement between the Pennsylvania Department of Human Services and the University of Pittsburgh. Authors (A.J.G., G.C., W.F.G., J.M.D.) are currently receiving grant support from the NIH, CDC (U01-CE002496), and/or the VA. W.G. is supported by a VA HSR&D Career Development Award (09-207). The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government. No other substantial conflicts of interest occur from the authors for the work contained within this manuscript. NR 39 TC 4 Z9 4 U1 4 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1932-0620 EI 1935-3227 J9 J ADDICT MED JI J. Addict. Med. PD NOV-DEC PY 2015 VL 9 IS 6 BP 470 EP 477 DI 10.1097/ADM.0000000000000164 PG 8 WC Substance Abuse SC Substance Abuse GA DC9CR UT WOS:000369519000009 PM 26517324 ER PT J AU Mao, JR AF Mao, Jianren TI Clinical Diagnosis of Opioid-Induced Hyperalgesia SO REGIONAL ANESTHESIA AND PAIN MEDICINE LA English DT Editorial Material ID THERAPY; PAIN C1 [Mao, Jianren] Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, MGH Ctr Translat Pain Res,Div Pain Med,Sch Med, Boston, MA 02114 USA. RP Mao, JR (reprint author), Harvard Univ, Sch Med, Dept Anesthesia Crit Care & Pain Med, Massachusetts Gen Hosp, 15 Parkman St,WACC 324, Boston, MA 02114 USA. EM jmao@mgh.harvard.edu FU NIDA NIH HHS [R01 DA036564] NR 5 TC 1 Z9 2 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1098-7339 EI 1532-8651 J9 REGION ANESTH PAIN M JI Region. Anesth. Pain Med. PD NOV-DEC PY 2015 VL 40 IS 6 BP 663 EP 664 DI 10.1097/AAP.0000000000000317 PG 2 WC Anesthesiology SC Anesthesiology GA DD0OG UT WOS:000369618700001 PM 26488079 ER PT J AU Jain, S Keys, D Ljubanovic, D Edelstein, CL Jani, A AF Jain, Swati Keys, Daniel Ljubanovic, Danica Edelstein, Charles L. Jani, Alkesh TI Protection Against Cold Storage-Induced Renal Tubular Cell Apoptosis SO TRANSPLANTATION LA English DT Article ID SERINE-PROTEASE ACTIVITY; DELAYED GRAFT FUNCTION; OMI/HTRA2 PROTEASE; CEREBRAL ISCHEMIA/REPERFUSION; RISK-FACTORS; DEATH; INHIBITOR; KIDNEY; REPERFUSION; ISCHEMIA AB Background. Prolonged cold storage (CS) of donor kidneys is associated with tubular cell apoptosis and caspase-3 activation. We have previously shown that pancaspase inhibition prevents CS-associated tubular apoptosis. Because of the nonspecific nature of pancaspase inhibitors, which block all caspases including proinflammatory caspase-1, the effect of specific caspase-3 inhibition during CS is unknown. X-linked inhibitor of apoptosis (XIAP) is the most potent naturally occurring specific inhibitor of caspase-3. We hypothesized that prolonged CS would decrease XIAP, whereas upregulation of XIAP with the novel compound UCF-101 would protect against caspase-3 activation and tubular cell apoptosis. Methods. LLC-PK1 tubular cells and whole kidneys from C57BL/6 mice were subjected to prolonged CS with or without UCF-101, and examined for XIAP, caspase-3, and tubular apoptosis. Results. Tubular cells subjected to prolonged CS in vitro demonstrated significantly decreased XIAP and significantly increased apoptosis, caspase-3 protein and activity. UCF-101 treatment significantly increased XIAP, significantly decreased capsase-3 protein and activity, and protected against apoptosis. To determine the therapeutic significance, whole kidneys were subjected to prolonged CS with UCF-101. UCF-101 significantly increased XIAP in donor kidneys and protected against apoptosis. Conclusions. Prolonged CS of tubular cells in vitro and whole mouse kidneys ex vivo is associated with loss of XIAP and subsequent tubular cell apoptosis. UCF-101 protects against the loss of XIAP during prolonged CS both in vitro and ex vivo, and is associated with significantly reduced tubular cell apoptosis. UCF-101 may represent an attractive approach to improve organ preservation. C1 [Jain, Swati; Keys, Daniel; Edelstein, Charles L.; Jani, Alkesh] Univ Colorado, Dept Renal Dis & Hypertens, Denver, CO 80202 USA. [Edelstein, Charles L.; Jani, Alkesh] Denver Vet Affairs Med Ctr, Renal Sect, Denver, CO USA. [Ljubanovic, Danica] Univ Zagreb, Hosp Dubrava, SOM, Dept Pathol, Zagreb 41000, Croatia. RP Jani, A (reprint author), Univ Colorado Denver, Div Renal Dis & Hypertens, 12700 East 19th Ave,C281, Aurora, CO 80045 USA. EM Alkesh.jani@ucdenver.edu FU BLRD VA [I01 BX001737]; NIDDK NIH HHS [1 R03 DK96151-01, R03 DK096151, T32 DK007135] NR 28 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD NOV PY 2015 VL 99 IS 11 BP 2311 EP 2316 DI 10.1097/TP.0000000000000774 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DC2ZJ UT WOS:000369087800025 PM 26177086 ER PT J AU Keating, BJ van Setten, J Jacobson, PA Holmes, MV Verma, SS Chandrupatla, HR Nair, N Gao, H Li, YR Chang, BL Wong, C Phillips, R Cole, BS Mukhtar, E Zhang, WJ Cao, HZ Mohebnasab, M Hou, CP Lee, T Steel, L Shaked, O Garifallou, J Miller, MB Karczewski, KJ Akdere, A Gonzalez, A Lloyd, KM McGinn, D Michaud, Z Colasacco, A Lek, M Fu, Y Pawashe, M Guettouche, T Himes, A Perez, L Guan, WH Wu, BL Schladt, D Menon, M Zhang, ZY Tragante, V de Jonge, N Otten, HG de Weger, RA van de Graaf, EA Baan, CC Manintveld, OC De Vlaminck, I Piening, BD Strehl, C Shaw, M Snieder, H Klintmalm, GB O'Leary, JG Amaral, S Goldfarb, S Rand, E Rossano, JW Kohli, U Heeger, P Stahl, E Christie, JD Fuentes, MH Levine, JE Aplenc, R Schadt, EE Stranger, BE Kluin, J Potena, L Zuckermann, A Khush, K Alzahrani, AJ Al-Muhanna, FA Al-Ali, AK Al-Ali, R Al-Rubaish, AM Al-Mueilo, S Byrne, EM Miller, D Alexander, SI Onengut-Gumuscu, S Rich, SS Suthanthiran, M Tedesco, H Saw, CL Ragoussis, J Kfoury, AG Horne, B Carlquist, J Gerstein, MB Reindl-Schwaighofer, R Oberbauer, R Wijmenga, C Palmer, S Pereira, AC Segovia, J Alonso-Pulpon, LA Comez-Bueno, M Vilches, C Jaramillo, N de Borst, MH Naesens, M Hao, K MacArthur, D Balasubramanian, S Conlon, PJ Lord, GM Ritchie, MD Snyder, M Olthoff, KM Moore, JH Petersdorf, EW Kamoun, M Wang, J Monos, DS de Bakker, PIW Hakonarson, H Murphy, B Lankree, MB Garcia-Pavia, P Oetting, WS Birdwell, KA Bakker, SJL Israni, AK Shaked, A Asselbergs, FW AF Keating, Brendan J. van Setten, Jessica Jacobson, Pamala A. Holmes, Michael V. Verma, Shefali S. Chandrupatla, Hareesh R. Nair, Nikhil Gao, Hui Li, Yun R. Chang, Bao-Li Wong, Chanel Phillips, Randy Cole, Brian S. Mukhtar, Eyas Zhang, Weijia Cao, Hongzhi Mohebnasab, Maede Hou, Cuiping Lee, Takesha Steel, Laura Shaked, Oren Garifallou, James Miller, Michael B. Karczewski, Konrad J. Akdere, Abdullah Gonzalez, Ana Lloyd, Kelsey M. McGinn, Daniel Michaud, Zach Colasacco, Abigail Lek, Monkol Fu, Yao Pawashe, Mayur Guettouche, Toumy Himes, Aubree Perez, Leat Guan, Weihua Wu, Baolin Schladt, David Menon, Madhav Zhang, Zhongyang Tragante, Vinicius de Jonge, Nicolaas Otten, Henny G. de Weger, Roel A. van de Graaf, Ed A. Baan, Carla C. Manintveld, Olivier C. De Vlaminck, Iwijn Piening, Brian D. Strehl, Calvin Shaw, Mary Snieder, Harold Klintmalm, Goran B. O'Leary, Jacqueline G. Amaral, Sandra Goldfarb, Samuel Rand, Elizabeth Rossano, Joseph W. Kohli, Utkarsh Heeger, Peter Stahl, Eli Christie, Jason D. Fuentes, Maria Hernandez Levine, John E. Aplenc, Richard Schadt, Eric E. Stranger, Barbara E. Kluin, Jolanda Potena, Luciano Zuckermann, Andreas Khush, Kiran Alzahrani, Alhusain J. Al-Muhanna, Fahad A. Al-Ali, Amein K. Al-Ali, Rudaynah Al-Rubaish, Abdullah M. Al-Mueilo, Samir Byrne, Edna M. Miller, David Alexander, Stephen I. Onengut-Gumuscu, Suna Rich, Stephen S. Suthanthiran, Manikkam Tedesco, Helio Saw, Chee L. Ragoussis, Jiannis Kfoury, Abdallah G. Horne, Benjamin Carlquist, John Gerstein, Mark B. Reindl-Schwaighofer, Roman Oberbauer, Rainer Wijmenga, Cisca Palmer, Scott Pereira, Alexandre C. Segovia, Javier Alonso-Pulpon, Luis A. Comez-Bueno, Manuel Vilches, Carlos Jaramillo, Natalia de Borst, Martin H. Naesens, Maarten Hao, Ke MacArthur, DanielG. Balasubramanian, Suganthi Conlon, Peter J. Lord, Graham M. Ritchie, Marylyn D. Snyder, Michael Olthoff, Kim M. Moore, Jason H. Petersdorf, Effie W. Kamoun, Malek Wang, Jun Monos, Dimitri S. de Bakker, Paul I. W. Hakonarson, Hakon Murphy, Barbara Lankree, Matthew B. Garcia-Pavia, Pablo Oetting, William S. Birdwell, Kelly A. Bakker, Stephan J. L. Israni, Ajay K. Shaked, Abraham Asselbergs, Folkert W. CA Int Genetics & Translational Res T TI Design and Implementation of the International Genetics and Translational Research in Transplantation Network SO TRANSPLANTATION LA English DT Article ID GENOME-WIDE ASSOCIATION; ELECTRONIC MEDICAL-RECORDS; KIDNEY ALLOGRAFT FUNCTION; PRIMARY GRAFT DYSFUNCTION; CARDIAC TRANSPLANTATION; DONOR; POLYMORPHISM; RECIPIENTS; VARIANTS; GENOTYPE AB Background. Genetic association studies of transplantation outcomes have been hampered by small samples and highly complex multifactorial phenotypes, hindering investigations of the genetic architecture of a range of comorbidities which significantly impact graft and recipient life expectancy. We describe here the rationale and design of the International Genetics & Translational Research in Transplantation Network. The network comprises 22 studies to date, including 16 494 transplant recipients and 11 669 donors, of whom more than 5000 are of non-European ancestry, all of whom have existing genomewide genotype data sets. Methods. We describe the rich genetic and phenotypic information available in this consortium comprising heart, kidney, liver, and lung transplant cohorts. Results. We demonstrate significant power in International Genetics & Translational Research in Transplantation Network to detect main effect association signals across regions such as the MHC region as well as genomewide for transplant outcomes that span all solid organs, such as graft survival, acute rejection, new onset of diabetes after transplantation, and for delayed graft function in kidney only. Conclusions. This consortium is designed and statistically powered to deliver pioneering insights into the genetic architecture of transplant-related outcomes across a range of different solid-organ transplant studies. The study design allows a spectrum of analyses to be performed including recipient-only analyses, donor-recipient HLA mismatches with focus on loss-of-function variants and nonsynonymous single nucleotide polymorphisms. C1 [Keating, Brendan J.; Holmes, Michael V.; Chandrupatla, Hareesh R.; Nair, Nikhil; Gao, Hui; Chang, Bao-Li; Wong, Chanel; Phillips, Randy; Cole, Brian S.; Mukhtar, Eyas; Mohebnasab, Maede; Lee, Takesha; Steel, Laura; Shaked, Oren; Akdere, Abdullah; Gonzalez, Ana; Lloyd, Kelsey M.; McGinn, Daniel; Michaud, Zach; Colasacco, Abigail; Himes, Aubree; Perez, Leat; Shaw, Mary; Olthoff, Kim M.; Shaked, Abraham] Hosp Univ Penn, Penn Transplant Inst, Philadelphia, PA 19104 USA. [Keating, Brendan J.] Univ Penn, Dept Pediat, Perleman Sch Med, Philadelphia, PA 19104 USA. [Keating, Brendan J.; Chandrupatla, Hareesh R.; Nair, Nikhil; Gao, Hui; Li, Yun R.; Chang, Bao-Li; Wong, Chanel; Mukhtar, Eyas; Hou, Cuiping; Lee, Takesha; Steel, Laura; Garifallou, James; Guettouche, Toumy; Himes, Aubree; Monos, Dimitri S.; Hakonarson, Hakon] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [van Setten, Jessica; Tragante, Vinicius; de Jonge, Nicolaas; Asselbergs, Folkert W.] Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands. [Jacobson, Pamala A.] Univ Minnesota, Coll Pharm, Minneapolis, MN 55455 USA. [Verma, Shefali S.; Ritchie, Marylyn D.] Penn State Univ, Ctr Syst Genom, University Pk, PA 16802 USA. [Li, Yun R.] Univ Penn, Perelman Sch Med, Med Scientist Training Program, Philadelphia, PA 19104 USA. [Cole, Brian S.] Univ Penn, Perelman Sch Med, Inst Biomed Informat, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Zhang, Weijia; Menon, Madhav] Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, New York, NY 10029 USA. [Cao, Hongzhi; Wang, Jun] BGI Shenzhen, Shenzhen, Peoples R China. [Cao, Hongzhi] Univ Copenhagen, Dept Biol, Copenhagen, Denmark. [Miller, Michael B.] Univ Minnesota, Dept Psychol, Minneapolis, MN USA. [Karczewski, Konrad J.; Lek, Monkol] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Karczewski, Konrad J.; Lek, Monkol; MacArthur, DanielG.] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Karczewski, Konrad J.; Lek, Monkol; MacArthur, DanielG.] MIT, Cambridge, MA 02139 USA. [Fu, Yao; Balasubramanian, Suganthi] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT USA. [Pawashe, Mayur; Balasubramanian, Suganthi] Yale Univ, Dept Biochem & Mol Biophys, New Haven, CT USA. [Guan, Weihua; Wu, Baolin] Univ Minnesota, Div Biostat, Minneapolis, MN USA. [Schladt, David] Hennepin Cty Med Ctr, Minneapolis Med Res Fdn, Minneapolis, MN 55415 USA. [Zhang, Zhongyang] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Otten, Henny G.] Univ Med Ctr, Dept Immunol, Utrecht, Netherlands. [de Weger, Roel A.] Univ Med Ctr, Dept Pathol, Utrecht, Netherlands. [van de Graaf, Ed A.] Univ Med Ctr Utrecht, Dept Pulm Dis, Utrecht, Netherlands. [Baan, Carla C.] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands. [Manintveld, Olivier C.] Erasmus Univ, Med Ctr, Dept Cardiol, Rotterdam, Netherlands. [De Vlaminck, Iwijn] Stanford Univ, Dept Bioengn & Appl Phys, Stanford, CA 94305 USA. [De Vlaminck, Iwijn; Piening, Brian D.] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA. [Piening, Brian D.; Strehl, Calvin; Khush, Kiran; Snyder, Michael] Stanford Univ, Sch Med, Stanford Cardiovasc Inst, Stanford, CA 94305 USA. [Snieder, Harold] Univ Groningen, Univ Med Ctr Groningen, Unit Genet Epidemiol & Bioinformat, Dept Epidemiol, NL-9700 AB Groningen, Netherlands. [Klintmalm, Goran B.] Baylor Univ, Med Ctr, Baylor Simmons Transplant Inst, Dallas, TX USA. [O'Leary, Jacqueline G.] Baylor Univ, Med Ctr, Div Hepatol, Annette C & Harold C Simmons Transplant Inst, Dallas, TX USA. [Amaral, Sandra] Childrens Hosp Philadelphia, Div Nephrol, Philadelphia, PA 19104 USA. [Amaral, Sandra] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Goldfarb, Samuel] Childrens Hosp Philadelphia, Div Pulm Med, Philadelphia, PA 19104 USA. [Rand, Elizabeth] Univ Penn, Perelman Sch Med, Div Gastroenterol, Philadelphia, PA 19104 USA. [Rossano, Joseph W.; Kohli, Utkarsh] Childrens Hosp Philadelphia, Div Pediat Cardiol, Philadelphia, PA 19104 USA. [Heeger, Peter] Icahn Sch Med Mt Sinai, Div Nephrol, New York, NY 10029 USA. [Heeger, Peter; Murphy, Barbara] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA. [Stahl, Eli; Schadt, Eric E.; Hao, Ke] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA. [Christie, Jason D.] Univ Penn, Div Pulm Allergy & Crit Care, Philadelphia, PA 19104 USA. [Fuentes, Maria Hernandez; Lord, Graham M.] Kings Coll London, London WC2R 2LS, England. [Levine, John E.] Univ Michigan, Blood & Marrow Transplant Program, Ann Arbor, MI 48109 USA. [Aplenc, Richard] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. [Stranger, Barbara E.] Univ Chicago, Med Genet Sect, Chicago, IL 60637 USA. [Kluin, Jolanda] Univ Med Ctr Utrecht, Dept Cardiothorac Surg, Utrecht, Netherlands. [Potena, Luciano] Univ Bologna, Cardiovasc Dept, Heart Failure & Heart Transplant Unit, I-40126 Bologna, Italy. [Zuckermann, Andreas] Med Univ Vienna, Dept Cardiac Surg, Vienna, Austria. [Alzahrani, Alhusain J.] King Saud Univ, Coll Appl Med Sci, Riyadh, Saudi Arabia. [Al-Muhanna, Fahad A.; Al-Ali, Amein K.; Al-Rubaish, Abdullah M.; Al-Mueilo, Samir] Univ Dammam, Coll Med, Dammam, Saudi Arabia. [Al-Ali, Rudaynah] Univ Dammam, King Fahd Hosp, Dept Internal Med, Dammam, Saudi Arabia. [Byrne, Edna M.; Gerstein, Mark B.] Univ Queensland, Brisbane, Qld, Australia. [Miller, David] Univ Queensland, IMB, Queensland Ctr Med Genom, Brisbane, Qld 4072, Australia. [Miller, David] St Vincents Hosp, Garvan Inst Med Res, Kinghorn Ctr Clin Gen, Darlinghurst, NSW 2010, Australia. [Alexander, Stephen I.] Univ Sydney, Childrens Hosp Westmead, Ctr Kidney Res, Sydney, NSW 2006, Australia. [Onengut-Gumuscu, Suna; Rich, Stephen S.; Moore, Jason H.] Univ Virginia, Dept Publ Hlth Sci, Ctr Publ Hlth Gen, Charlottesville, VA 22903 USA. [Suthanthiran, Manikkam] Weill Cornell Med Coll, Dept Med, Div Nephrol & Hypertens, New York, NY USA. [Tedesco, Helio] Hosp Rim & Hipertensao, Div Nephrol, Sao Paulo, Brazil. [Saw, Chee L.] McGill Univ, Ctr Hlth, Div Hematol, HLA Lab, Montreal, PQ, Canada. [Ragoussis, Jiannis] McGill Univ, Montreal, PQ, Canada. [Ragoussis, Jiannis] Genome Quebec Innovat Ctr, Montreal, PQ, Canada. [Kfoury, Abdallah G.; Horne, Benjamin; Carlquist, John; Gerstein, Mark B.] Intermt Heart Inst, Murray, UT USA. [Reindl-Schwaighofer, Roman; Oberbauer, Rainer] Univ Vienna, Dept Internal Med 3, Div Nephrol Dialysis, A-1010 Vienna, Austria. [Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. [Palmer, Scott] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA. [Pereira, Alexandre C.] Univ Sao Paulo, Sch Med, Heart Inst InCor, Lab Genet & Mol Cardiol, Sao Paulo, Brazil. [Segovia, Javier; Alonso-Pulpon, Luis A.; Comez-Bueno, Manuel; Jaramillo, Natalia; Garcia-Pavia, Pablo] Hosp Univ Puerta Hierro Majadahonda, Dept Cardiol, Heart Transplant Unit, Madrid, Spain. [Vilches, Carlos] Hosp Univ Puerta Hierro Majadahonda, Dept Immunol, Madrid, Spain. [de Borst, Martin H.; Bakker, Stephan J. L.] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Div Nephrol, Groningen, Netherlands. [Naesens, Maarten] Univ Hosp Leuven, Dept Nephrol & Renal Transplantat, Leuven, Belgium. [MacArthur, DanielG.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Conlon, Peter J.] Beaumont Hosp, Dept Transplantat & Renal Med, Dublin 9, Ireland. [Snyder, Michael] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. [Petersdorf, Effie W.] Washington Univ, Sch Med Seattle, Fred Hutchinson Canc Res Ctr, Div Med Oncol, St Louis, MO 63130 USA. [Kamoun, Malek; Monos, Dimitri S.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Ctr Mol Med, Dept Med Genet, Utrecht, Netherlands. [de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, Utrecht, Netherlands. [Murphy, Barbara] Icahn Sch Med Mt Sinai, Div Nephrol, New York, NY 10029 USA. [Lankree, Matthew B.] McMaster Univ, Dept Med, Hamilton, ON, Canada. [Oetting, William S.] Univ Minnesota, Expt & Clin Pharmacol, Minneapolis, MN USA. [Birdwell, Kelly A.] Vanderbilt Univ, Ctr Med, Dept Med, Nashville, TN 37232 USA. [Israni, Ajay K.] Univ Minnesota, Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. [Asselbergs, Folkert W.] UCL, Inst Cardiovasc Sci, London, England. [Asselbergs, Folkert W.] ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands. RP Keating, BJ (reprint author), Hosp Univ Penn, Div Transplantat, 2 Dulles,3400 Spruce St, Philadelphia, PA 19104 USA. EM bkeating@mail.med.upenn.edu; isran001@umn.edu; Abraham.Shaked@uphs.upenn.edu; F.W.Asselbergs@umcutrecht.nl RI Vilches, Carlos/G-1471-2012; Hernandez-Fuentes, Maria/B-5011-2010; Wijmenga, Cisca/D-2173-2009 OI Birdwell, Kelly/0000-0002-7996-3947; Vilches, Carlos/0000-0002-0300-9225; Hernandez-Fuentes, Maria/0000-0002-7558-9441; De Vlaminck, Iwijn/0000-0001-6085-7311; Stranger, Barbara/0000-0001-9021-7331; NR 52 TC 0 Z9 0 U1 4 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD NOV PY 2015 VL 99 IS 11 BP 2401 EP 2412 DI 10.1097/TP.0000000000000913 PG 12 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DC2ZJ UT WOS:000369087800037 ER PT J AU Zanchi, D Brody, AL Montandon, ML Kopel, R Emmert, K Preti, MG Van de Ville, D Haller, S AF Zanchi, Davide Brody, Arthur L. Montandon, Marie-Louise Kopel, Rotem Emmert, Kirsten Preti, Maria Giulia Van de Ville, Dimitri Haller, Sven TI Cigarette smoking leads to persistent and dose-dependent alterations of brain activity and connectivity in anterior insula and anterior cingulate SO ADDICTION BIOLOGY LA English DT Article DE Craving; nicotine; smoking ID SUSTAINED-RELEASE BUPROPION; SUBJECT DIFFUSION DATA; FUNCTIONAL CONNECTIVITY; NICOTINE ABSTINENCE; SPATIAL STATISTICS; VOXELWISE ANALYSIS; NEURAL ACTIVITY; SMOKERS; CESSATION; MOTION AB Although many smokers try to quit smoking, only about 20-25 percent will achieve abstinence despite 6months or more of gold-standard treatment. This low success rate suggests long-term changes in the brain related to smoking, which remain poorly understood. We compared ex-smokers to both active smokers and non-smokers using functional magnetic resonance imaging (fMRI) to explore persistent modifications in brain activity and network organization. This prospective and consecutive study includes 18 non-smokers (29.5 +/- 6.7years of age, 11 women), 14 smokers (10 cigarettes a day >2years of smoking, 29.3 +/- 6.0years of age, 10 women) and 14 ex-smokers (>1year of quitting 30.5 +/- 5.7years of age, 10 women). Participants underwent a block-design fMRI study contrasting smoking cue with control (neutral cue) videos. Data analyses included task-related general linear model, seed-based functional connectivity, voxel-based morphometry (VBM) of gray matter and tract-based spatial statistics (TBSS) of white matter. Smoking cue videos versus control videos activated the right anterior insula in ex-smokers compared with smokers, an effect correlating with cumulative nicotine intake (pack-years). Moreover, ex-smokers had a persistent decrease in functional connectivity between right anterior insula and anterior cingulate cortex (ACC) compared with control participants, but similar to active smokers. Potentially confounding alterations in gray or white matter were excluded in VBM and TBSS analyses. In summary, ex-smokers with long-term nicotine abstinence have persistent and dose-dependent brain network changes notably in the right anterior insula and its connection to the ACC. C1 [Zanchi, Davide; Montandon, Marie-Louise; Kopel, Rotem; Emmert, Kirsten; Preti, Maria Giulia; Van de Ville, Dimitri] Univ Hosp Geneva, Dept Imaging & Med Informat, Geneva, Switzerland. [Zanchi, Davide; Montandon, Marie-Louise; Kopel, Rotem; Emmert, Kirsten; Preti, Maria Giulia; Van de Ville, Dimitri] Univ Geneva, Fac Med, CH-1211 Geneva 4, Switzerland. [Brody, Arthur L.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 USA. [Brody, Arthur L.] VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. [Brody, Arthur L.] VA Greater Los Angeles Healthcare Syst, Dept Res, Los Angeles, CA USA. [Kopel, Rotem; Preti, Maria Giulia; Van de Ville, Dimitri] Ecole Polytech Fed Lausanne, Inst Bioengn, CH-1015 Lausanne, Switzerland. [Haller, Sven] Univ Geneva, Fac Med, CH-1211 Geneva 4, Switzerland. [Haller, Sven] Uppsala Univ, Dept Surg Sci, Radiol, Uppsala, Sweden. [Haller, Sven] Univ Hosp Freiburg, Dept Neuroradiol, Freiburg, Germany. [Haller, Sven] Affidea Ctr Diagnost Radiol Carouge CDRC, Geneva, Switzerland. RP Haller, S (reprint author), Affidea Ctr Diagnost Radiol Carouge CDRC, Geneva, Switzerland. EM sven.haller@me.com OI Van De Ville, Dimitri/0000-0002-2879-3861; Haller, Sven/0000-0001-7433-0203 FU Swiss National Foundation [320030_147126/1, 320030_127079/1, SNF PP00P2-146318]; Fonds Startup du Departement de Radiologie et Informatique Medicale in Geneva, Switzerland; National Institute on Drug Abuse [R01 DA20872]; Department of Veterans Affairs, Office of Research and Development (CSR&D Merit Review Award) [I01 CX000412]; Tobacco-Related Disease Research Program [23XT-0002] FX We want to thank all volunteers for their participation in the study. We also thank Prof. Dr. Christian Luscher for his constructive help during the manuscript preparation. The study was supported by Swiss National Foundation grants SNF project 320030_147126/1, SNF project 320030_127079/1 and SNF PP00P2-146318 as well as the Fonds Startup du Departement de Radiologie et Informatique Medicale in Geneva, Switzerland. Dr. Brody is supported by grants from the National Institute on Drug Abuse (R01 DA20872), the Department of Veterans Affairs, Office of Research and Development (CSR&D Merit Review Award I01 CX000412) and the Tobacco-Related Disease Research Program (no. 23XT-0002). NR 49 TC 4 Z9 4 U1 5 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1355-6215 EI 1369-1600 J9 ADDICT BIOL JI Addict. Biol. PD NOV PY 2015 VL 20 IS 6 BP 1033 EP 1041 DI 10.1111/adb.12292 PG 9 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA DC1QN UT WOS:000368991600004 PM 26303184 ER PT J AU Lax, T Long, AD Banerji, A AF Lax, Timothy Long, Aidan Banerji, Aleena TI Skin Testing in the Evaluation and Management of Carboplatin-Related Hypersensitivity Reactions SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE LA English DT Review DE Carboplatin; Hypersensitivity reaction; Allergy; Skin testing; Predictive value; Timing; Management ID GYNECOLOGIC MALIGNANCIES; RISK STRATIFICATION; COMPLEX SALTS; DESENSITIZATION; CHEMOTHERAPY; ALLERGY; CANCER; CISPLATIN; PLATINUM; PROTOCOL AB Carboplatin-induced hypersensitivity reactions (HSRs) are a frequent occurrence in patients being retreated for malignancy. The most common and severe reactions are thought to be IgE mediated. Currently, skin testing is the only method used clinically to identify individuals sensitized to carboplatin. Despite almost 20 years of clinical use, a standardized approach to skin testing and its use in the management of carboplatin HSRs has not been well established. We review the utility of carboplatin skin testing and discuss factors that influence the interpretation of skin testing results. A risk stratification strategy using skin testing and desensitization to manage patients with carboplatin HSRs is proposed. (C) 2015 American Academy of Allergy, Asthma & Immunology C1 [Lax, Timothy; Long, Aidan; Banerji, Aleena] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol,Dept Med, Boston, MA USA. RP Lax, T (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, 55 Fruit St, Boston, MA 02114 USA. EM tlax@partners.org NR 35 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2198 EI 2213-2201 J9 J ALLER CL IMM-PRACT JI J. Allergy Clin. Immunol.-Pract. PD NOV-DEC PY 2015 VL 3 IS 6 BP 856 EP 862 DI 10.1016/j.jaip.2015.07.003 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA DB7AH UT WOS:000368666300004 PM 26432514 ER PT J AU Leung, J Mehrzad, R Hundal, NV Alejos, A Hesterberg, PE Katz, AJ Yuan, Q Shreffler, WG AF Leung, John Mehrzad, Raman Hundal, Navneet Virk Alejos, Alexandra Hesterberg, Paul E. Katz, Aubrey J. Yuan, Qian Shreffler, Wayne G. TI Longitudinal Perspective on Managing Refractory Eosinophilic Esophagitis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE LA English DT Article DE Eosinophilic esophagitis; Management; Treatment; Refractory ID ELIMINATION DIET; CHILDREN; MILK AB BACKGROUND: One half to one third of the patients with eosinophilic esophagitis (EoE) do not achieve histological remission on initial treatment. We wondered whether these treatment failure patients are a distinct clinical subset. OBJECTIVE: To analyze EoE treatment outcomes in a predominantly pediatric population. METHODS: We reviewed 100 serial EoE cases at Massachusetts General Hospital starting from 2007. We defined histological remission as peak esophageal eosinophil count of less than 10/hpf. RESULTS: Ninety-seven patients with EoE underwent initial treatments: 54 of 81 (67%) responded to dietary therapy, and 9 of 16 (56%) responded to topical glucocorticoids. Of the 34 who failed initial treatment, 24 underwent various second treatment regimens and 54% (13 of 24) responded. Eight of the remaining 11 who failed second treatment underwent additional treatments and 2 ultimately responded. The overall response rate by intent-to-treat analysis increased from 65% (63 of 97) with initial treatment to 78% (76 of 97) with rescue treatment, and further to 80% (78 of 97) with multiple treatments. On a per-protocol basis, the overall response rate was 93% (78 of 84); however, patients who failed the first 2 rounds of therapy had only a 20% response rate. Patients who responded to initial treatment were found to have more symptoms and endoscopic abnormalities. Comparison of patients who failed both initial and rescue therapy with those who responded to rescue therapy did not identify any differentiating clinical features. CONCLUSIONS: More than half of the patients who failed initial EoE treatment could still achieve histological remission with individualized rescue treatments. No clinical features could predict response to rescue treatment. (C) 2015 American Academy of Allergy, Asthma & Immunology C1 [Leung, John; Mehrzad, Raman; Hundal, Navneet Virk; Alejos, Alexandra; Hesterberg, Paul E.; Katz, Aubrey J.; Yuan, Qian; Shreffler, Wayne G.] Massachusetts Gen Hosp, Food Allergy Ctr, Boston, MA 02114 USA. [Leung, John; Hundal, Navneet Virk; Shreffler, Wayne G.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, 55 Fruit St,CPZS 557, Boston, MA 02114 USA. [Leung, John] Tufts Med Ctr, Food Allergy Ctr, Boston, MA USA. [Leung, John] Floating Hosp, Boston, MA USA. [Katz, Aubrey J.; Yuan, Qian] MassGen Hosp Children, Pediat Gastroenterol, Boston, MA USA. RP Shreffler, WG (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, 55 Fruit St,CPZS 557, Boston, MA 02114 USA. EM wshreffler@mgh.harvard.edu FU Demarest Lloyd Jr Foundation FX This study was supported by the Demarest Lloyd Jr Foundation. NR 13 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2198 EI 2213-2201 J9 J ALLER CL IMM-PRACT JI J. Allergy Clin. Immunol.-Pract. PD NOV-DEC PY 2015 VL 3 IS 6 BP 951 EP 956 DI 10.1016/j.jaip.2015.06.024 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA DB7AH UT WOS:000368666300022 PM 26342740 ER PT J AU Otani, IM Kuhlen, JL Blumenthal, KG Guyer, A Banerji, A AF Otani, Iris M. Kuhlen, James L., Jr. Blumenthal, Kimberly G. Guyer, Autumn Banerji, Aleena TI A role for vancomycin epicutaneous skin testing in the evaluation of perioperative anaphylaxis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE LA English DT Letter ID ANESTHESIA; ALLERGY C1 [Otani, Iris M.; Kuhlen, James L., Jr.; Blumenthal, Kimberly G.; Banerji, Aleena] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Cox 201 Allergy Associates, Boston, MA 02114 USA. [Otani, Iris M.; Kuhlen, James L., Jr.; Blumenthal, Kimberly G.; Banerji, Aleena] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Blumenthal, Kimberly G.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Guyer, Autumn] Beth Israel Deaconess Med Ctr, Dept Med, Div Allergy & Inflammat, Boston, MA 02215 USA. RP Otani, IM (reprint author), Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Cox 201 Allergy Associates, Boston, MA 02114 USA. EM iotani@partners.org FU NHLBI NIH HHS [T32 HL116275] NR 11 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2198 EI 2213-2201 J9 J ALLER CL IMM-PRACT JI J. Allergy Clin. Immunol.-Pract. PD NOV-DEC PY 2015 VL 3 IS 6 BP 984 EP 985 DI 10.1016/j.jaip.2015.06.017 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA DB7AH UT WOS:000368666300033 PM 26246124 ER PT J AU Chowdhury, F Mather, AE Begum, YA Asaduzzaman, M Baby, N Sharmin, S Biswas, R Uddin, MI LaRocque, RC Harris, JB Calderwood, SB Ryan, ET Clemens, JD Thomson, NR Qadri, F AF Chowdhury, Fahima Mather, Alison E. Begum, Yasmin Ara Asaduzzaman, Muhammad Baby, Nabilah Sharmin, Salma Biswas, Rajib Uddin, Muhammad Ikhtear LaRocque, Regina C. Harris, Jason B. Calderwood, Stephen B. Ryan, Edward T. Clemens, John D. Thomson, Nicholas R. Qadri, Firdausi TI Vibrio cholerae Serogroup O139: Isolation from Cholera Patients and Asymptomatic Household Family Members in Bangladesh between 2013 and 2014 SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID AQUATIC ENVIRONMENT; SYNONYM BENGAL; EL-TOR; EPIDEMIC; TRANSMISSION; CONTACTS; SEQUENCE; STRAIN; DHAKA; TOOL AB Background Cholera is endemic in Bangladesh, with outbreaks reported annually. Currently, the majority of epidemic cholera reported globally is El Tor biotype Vibrio cholerae isolates of the serogroup O1. However, in Bangladesh, outbreaks attributed to V. cholerae serogroup O139 isolates, which fall within the same phylogenetic lineage as the O1 serogroup isolates, were seen between 1992 and 1993 and in 2002 to 2005. Since then, V. cholerae serogroup O139 has only been sporadically isolated in Bangladesh and is now rarely isolated elsewhere. Methods Here, we present case histories of four cholera patients infected with V. cholerae serogroup O139 in 2013 and 2014 in Bangladesh. We comprehensively typed these isolates using conventional approaches, as well as by whole genome sequencing. Phenotypic typing and PCR confirmed all four isolates belonging to the O139 serogroup. Findings Whole genome sequencing revealed that three of the isolates were phylogenetically closely related to previously sequenced El Tor biotype, pandemic 7, toxigenic V. cholerae O139 isolates originating from Bangladesh and elsewhere. The fourth isolate was a non-toxigenic V. cholerae that, by conventional approaches, typed as O139 serogroup but was genetically divergent from previously sequenced pandemic 7 V. cholerae lineages belonging to the O139 or O1 serogroups. Conclusion These results suggest that previously observed lineages of V. cholerae O139 persist in Bangladesh and can cause clinical disease and that a novel disease-causing non-toxigenic O139 isolate also occurs. C1 [Chowdhury, Fahima; Begum, Yasmin Ara; Asaduzzaman, Muhammad; Baby, Nabilah; Sharmin, Salma; Biswas, Rajib; Uddin, Muhammad Ikhtear; Clemens, John D.; Qadri, Firdausi] Int Ctr Diarrhoeal Dis Res, Icddr B, Dhaka, Bangladesh. [Mather, Alison E.; Thomson, Nicholas R.] Wellcome Trust Sanger Inst, Cambridge, England. [LaRocque, Regina C.; Harris, Jason B.; Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [LaRocque, Regina C.; Calderwood, Stephen B.; Ryan, Edward T.] Harvard Univ, Sch Med, Boston, MA USA. [Clemens, John D.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Los Angeles, CA USA. [Thomson, Nicholas R.] London Sch Hyg & Trop Med, Dept Pathogen Mol Biol, London WC1, England. RP Chowdhury, F (reprint author), Int Ctr Diarrhoeal Dis Res, Icddr B, Dhaka, Bangladesh. EM fqadri@icddrb.org OI Asaduzzaman, Muhammad/0000-0001-9048-7980 FU Bill & Melinda Gates Foundation [OPP50419]; National Institutes of Health [U01A1077883, R01AI106878, U01AI058935]; Government of Australia; Government of Bangladesh; Government of Canada; Government of Sweden; Government of UK; Wellcome Trust [098051]; Biotechnology and Biological Sciences Research Council [BB/M014088/1] FX This study was supported by a Grant OPP50419 from the Bill & Melinda Gates Foundation and National Institutes of Health (U01A1077883, R01AI106878 and U01AI058935). Additionally, the study was supported by the core grants of icddr, b. icddr, b is thankful to the Governments of Australia, Bangladesh, Canada, Sweden and the UK for providing core/unrestricted support. AEM and NRT were supported by Wellcome Trust grant 098051. AEM is supported by Biotechnology and Biological Sciences Research Council grant BB/M014088/1. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 0 Z9 0 U1 1 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD NOV PY 2015 VL 9 IS 11 AR e0004183 DI 10.1371/journal.pntd.0004183 PG 11 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA DB2NA UT WOS:000368344400016 PM 26562418 ER PT J AU Miller, M Wang, Y Moon, JJ Chong, AS Alegre, ML AF Miller, Michelle Wang, Ying Moon, James J. Chong, Anita S. Alegre, Maria-Luisa TI ENDOGENOUS GRAFT-SPECIFIC T CELL POPULATIONS EXHIBIT DISTINCT TCR AVIDITY PROFILES DURING ACUTE REJECTION AND TOLERANCE. SO TRANSPLANTATION LA English DT Meeting Abstract CT 14th Transplantation Science Symposium of the Transplantation-Society (TSS) CY NOV 11-13, 2015 CL Lorne, AUSTRALIA SP Transplantat Soc C1 [Miller, Michelle; Wang, Ying; Alegre, Maria-Luisa] Univ Chicago, Rheumatol Sect, Med, Chicago, IL 60637 USA. [Moon, James J.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Chong, Anita S.] Univ Chicago, Surg, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD NOV PY 2015 VL 99 IS 11 SU 1 MA 125 BP S3 EP S3 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DB6LG UT WOS:000368625900007 ER PT J AU Tena, A Sachs, DH Mallard, C Yang, YG Tasaki, M Farkash, E Colvin, R Leonard, DA Hawley, R AF Tena, Aseda Sachs, David H. Mallard, Christopher Yang, Yong-Guang Tasaki, Masayuki Farkash, Evan Colvin, Robert Leonard, David A. Hawley, Robert TI PROLONGED SURVIVAL OF PORCINE SKIN ON BABOONS FOLLOWING ADMINISTRATION OF PORCINE CELLS EXPRESSING HUMAN CD47. SO TRANSPLANTATION LA English DT Meeting Abstract CT 14th Transplantation Science Symposium of the Transplantation-Society (TSS) CY NOV 11-13, 2015 CL Lorne, AUSTRALIA SP Transplantat Soc C1 [Tena, Aseda; Sachs, David H.; Mallard, Christopher; Tasaki, Masayuki; Leonard, David A.; Hawley, Robert] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Farkash, Evan; Colvin, Robert] Massachusetts Gen Hosp, Pathol, Boston, MA 02114 USA. [Yang, Yong-Guang] Columbia Univ, Columbia Ctr Translat Immunol, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD NOV PY 2015 VL 99 IS 11 SU 1 MA 314 BP S46 EP S46 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DB6LG UT WOS:000368625900084 ER PT J AU Drain, PK AF Drain, Paul K. TI Implications of Repealing the Cuban Embargo for US Medicine and Public Health SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 [Drain, Paul K.] Univ Washington, Sch Med, Dept Global Hlth, Seattle, WA USA. [Drain, Paul K.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Drain, Paul K.] Univ Washington, Sch Med, Dept Epidemiol, Seattle, WA USA. [Drain, Paul K.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [Drain, Paul K.] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Drain, PK (reprint author), 325 Ninth Ave,UW Box 359927, Seattle, WA 98104 USA. EM pkdrain@uw.edu NR 6 TC 1 Z9 1 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 2015 VL 105 IS 11 BP 2210 EP 2211 DI 10.2105/AJPH.2015.302894 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DB2KJ UT WOS:000368336700021 PM 26378862 ER PT J AU Jacoby, GA Corcoran, MA Hooper, DC AF Jacoby, George A. Corcoran, Marian A. Hooper, David C. TI Protective Effect of Qnr on Agents Other than Quinolones That Target DNA Gyrase SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ANTIBIOTIC SIMOCYCLINONE D8; ESCHERICHIA-COLI; TOPOISOMERASE-IV; MICROCIN B17; IN-VITRO; STREPTOMYCES-ANTIBIOTICUS; STAPHYLOCOCCUS-AUREUS; KLEBSIELLA-PNEUMONIAE; CRYSTAL-STRUCTURE; BACTERIAL-GROWTH AB Qnr is a plasmid-encoded and chromosomally determined protein that protects DNA gyrase and topoisomerase IV from inhibition by quinolones. Despite its prevalence worldwide and existence prior to the discovery of quinolones, its native function is not known. Other synthetic compounds and natural products also target bacterial topoisomerases. A number were studied as molecular probes to gain insight into how Qnr acts. Qnr blocked inhibition by synthetic compounds with somewhat quinolone-like structure that target the GyrA subunit, such as the 2-pyridone ABT-719, the quinazoline-2,4-dione PD 0305970, and the spiropyrimidinetrione pyrazinyl-alkynyl-tetrahydroquinoline (PAT), indicating that Qnr is not strictly quinolone specific, but Qnr did not protect against GyrA-targeting simocyclinone D8 despite evidence that both simocyclinone D8 and Qnr affect DNA binding to gyrase. Qnr did not affect the activity of tricyclic pyrimidoindole or pyrazolopyridones, synthetic inhibitors of the GyrB subunit, or nonsynthetic GyrB inhibitors, such as coumermycin A1, novobiocin, gyramide A, or microcin B17. Thus, in this set of compounds the protective activity of Qnr was confined to those that, like quinolones, trap gyrase on DNA in cleaved complexes. C1 [Jacoby, George A.; Corcoran, Marian A.] Lahey Hosp & Med Ctr, Burlington, MA 01805 USA. [Hooper, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jacoby, GA (reprint author), Lahey Hosp & Med Ctr, Burlington, MA 01805 USA. EM gajacoby50@gmail.com FU U.S. Public Health Service, National Institutes of Health [R01 AI057576] FX This work was supported by grant R01 AI057576 from the U.S. Public Health Service, National Institutes of Health, to D.C.H. and G.A.J. NR 61 TC 4 Z9 4 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD NOV PY 2015 VL 59 IS 11 BP 6689 EP 6695 DI 10.1128/AAC.01292-15 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA DB0ZR UT WOS:000368238100003 PM 26239981 ER PT J AU Lapointe, HR Dong, W Lee, GQ Bangsberg, DR Martin, JN Mocello, AR Boum, Y Karakas, A Kirkby, D Poon, AFY Harrigan, PR Brumme, CJ AF Lapointe, H. R. Dong, W. Lee, G. Q. Bangsberg, D. R. Martin, J. N. Mocello, A. R. Boum, Y. Karakas, A. Kirkby, D. Poon, A. F. Y. Harrigan, P. R. Brumme, C. J. TI HIV Drug Resistance Testing by High-Multiplex "Wide" Sequencing on the MiSeq Instrument SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ANTIRETROVIRAL-NAIVE INDIVIDUALS; REVERSE-TRANSCRIPTASE; GENOTYPING SYSTEM; ANALYSIS TOOL; WHOLE-BLOOD; THERAPY; MUTATIONS; SPOTS; TECHNOLOGIES; PERFORMANCE AB Limited access to HIV drug resistance testing in low-and middle-income countries impedes clinical decision-making at the individual patient level. An efficient protocol to address this issue must be established to minimize negative therapeutic outcomes for HIV-1-infected individuals in such settings. This is an observational study to ascertain the potential of newer genomic sequencing platforms, such as the Illumina MiSeq instrument, to provide accurate HIV drug resistance genotypes for hundreds of samples simultaneously. Plasma samples were collected from Canadian patients during routine drug resistance testing (n = 759) and from a Ugandan study cohort (n = 349). Amplicons spanning HIV reverse transcriptase codons 90 to 234 were sequenced with both MiSeq sequencing and conventional Sanger sequencing methods. Sequences were evaluated for nucleotide concordance between methods, using coverage and mixture parameters for quality control. Consensus sequences were also analyzed for disparities in the identification of drug resistance mutations. Sanger and MiSeq sequencing was successful for 881 samples (80%) and 892 samples (81%), respectively, with 832 samples having results from both methods. Most failures were for samples with viral loads of <3.0 log(10) HIV RNA copies/ml. Overall, 99.3% nucleotide concordance between methods was observed. MiSeq sequencing achieved 97.4% sensitivity and 99.3% specificity in detecting resistance mutations identified by Sanger sequencing. Findings suggest that the Illumina MiSeq platform can yield high-quality data with a high-multiplex "wide" sequencing approach. This strategy can be used for multiple HIV subtypes, demonstrating the potential for widespread individual testing and annual population surveillance in resource-limited settings. C1 [Lapointe, H. R.; Dong, W.; Lee, G. Q.; Karakas, A.; Kirkby, D.; Poon, A. F. Y.; Harrigan, P. R.; Brumme, C. J.] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada. [Bangsberg, D. R.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Bangsberg, D. R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bangsberg, D. R.; Boum, Y.] Mbarara Univ Sci Technol, Mbarara, Uganda. [Martin, J. N.; Mocello, A. R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Poon, A. F. Y.; Harrigan, P. R.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. RP Harrigan, PR (reprint author), British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada. EM prharrigan@cfenet.ubc.ca; cbrumme@cfenet.ubc.ca RI Lee, Guinevere/D-4436-2017; OI Lee, Guinevere/0000-0002-9412-886X; Brumme, Chanson/0000-0003-2722-5288; Poon, Art/0000-0003-3779-154X FU Large-Scale Applied Research Project grant from Genome Canada FX This study was funded by a Large-Scale Applied Research Project grant from Genome Canada to P.R.H. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. NR 43 TC 6 Z9 6 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD NOV PY 2015 VL 59 IS 11 BP 6824 EP 6833 DI 10.1128/AAC.01490-15 PG 10 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA DB0ZR UT WOS:000368238100019 PM 26282425 ER PT J AU Chen, CH Villet, R Jacoby, GA Hooper, DC AF Chen, Chunhui Villet, Regis Jacoby, George A. Hooper, David C. TI Functions of a GyrBA Fusion Protein and Its Interaction with QnrB and Quinolones SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID COLI DNA GYRASE; ESCHERICHIA-COLI; TOPOISOMERASE; RESISTANCE; REPLICATION; STRAND AB In order to study the interactions between Escherichia coli DNA gyrase and the gyrase interacting protein QnrB in vivo, we constructed a gyrB-gyrA fusion and validated its ability to correct the temperature-sensitive growth of gyrA and gyrB mutants. Like wild-type gyrA, the gyrB-gyrA fusion complemented a quinolone-resistant gyrA mutant to increase susceptibility. It functioned as an active type II topoisomerase, catalyzed negative supercoiling of DNA, was inhibited by quinolone, and was protected by QnrB. C1 [Chen, Chunhui; Villet, Regis; Hooper, David C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Chen, Chunhui] Fudan Univ, Huashan Hosp, Inst Antibiot, Shanghai 200433, Peoples R China. [Chen, Chunhui] Natl Hlth & Family Planning Commiss, Key Lab Clin Pharmacol Antibiot, Shanghai, Peoples R China. [Jacoby, George A.] Lahey Hosp & Med Ctr, Burlington, MA USA. RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM dhooper@mgh.harvard.edu FU U.S. Public Health Service; National Institutes of Health [R01 AI057576]; China Scholarship Council [201306100049] FX This work was funded in part by a grant from the U.S. Public Health Service, National Institutes of Health (no. R01 AI057576) (to D.C.H. and G.A.J.). This work was also supported by a scholarship from the China Scholarship Council (no. 201306100049) (to C.C.). NR 17 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD NOV PY 2015 VL 59 IS 11 BP 7124 EP 7127 DI 10.1128/AAC.01845-15 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA DB0ZR UT WOS:000368238100061 PM 26324265 ER PT J AU Kradin, RL AF Kradin, Richard L. TI Honeycomb Lung Time for a Change SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID IDIOPATHIC PULMONARY-FIBROSIS AB The recent introduction of new US Food and Drug Administration-approved medications for the treatment of idiopathic pulmonary fibrosis/usual interstitial pneumonia raises important concerns about the accuracy of diagnosis. The term honeycomb lung, used widely by radiologists and pathologists in the diagnosis of usual interstitial pneumonia, represents a late stage of the disease and conveys no biological information. A new conception of end-stage lung disease in usual interstitial pneumonia, based on the dying back of the pulmonary acinus, is proposed, which may improve the sensitivity and specificity of the diagnosis and provide an understanding of its pathogenesis. C1 [Kradin, Richard L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kradin, Richard L.] Massachusetts Gen Hosp, Dept Pulm & Crit Care Med, Boston, MA 02114 USA. [Kradin, Richard L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Kradin, RL (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 253, Boston, MA 02114 USA. EM rkradin@partners.org NR 7 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 EI 1543-2165 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD NOV PY 2015 VL 139 IS 11 BP 1398 EP 1399 DI 10.5858/arpa.2015-0065-SA PG 2 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA DB3OT UT WOS:000368421700010 PM 26516937 ER PT J AU Robboy, SJ Gupta, S Crawford, JM Cohen, MB Karcher, DS Leonard, DGB Magnani, B Novis, DA Prystowsky, MB Powell, SZ Gross, DJ Black-Schaffer, WS AF Robboy, Stanley J. Gupta, Saurabh Crawford, James M. Cohen, Michael B. Karcher, Donald S. Leonard, Debra G. B. Magnani, Barbarajean Novis, David A. Prystowsky, Michael B. Powell, Suzanne Z. Gross, David J. Black-Schaffer, W. Stephen TI The Pathologist Workforce in the United States II. An Interactive Modeling Tool for Analyzing Future Qualitative and Quantitative Staffing Demands for Services SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID HEALTH-CARE WORKFORCE; ANATOMIC PATHOLOGY; BIOSPECIMENS; MANAGEMENT; CONSENSUS; EDUCATION; WORKLOAD; REDESIGN AB Context.-Pathologists are physicians who make diagnoses based on interpretation of tissue and cellular specimens (surgical/cytopathology, molecular/genomic pathology, autopsy), provide medical leadership and consultation for laboratory medicine, and are integral members of their institutions' interdisciplinary patient care teams. Objective.-To develop a dynamic modeling tool to examine how individual factors and practice variables can forecast demand for pathologist services. Design.-Build and test a computer-based software model populated with data from surveys and best estimates about current and new pathologist efforts. Results.-Most pathologists' efforts focus on anatomic (52%), laboratory (14%), and other direct services (8%) for individual patients. Population-focused services (12%) (eg, laboratory medical direction) and other professional responsibilities (14%) (eg, teaching, research, and hospital committees) consume the rest of their time. Modeling scenarios were used to assess the need to increase or decrease efforts related globally to the Affordable Care Act, and specifically, to genomic medicine, laboratory consolidation, laboratory medical direction, and new areas where pathologists' expertise can add value. Conclusions.-Our modeling tool allows pathologists, educators, and policy experts to assess how various factors may affect demand for pathologists' services. These factors include an aging population, advances in biomedical technology, and changing roles in capitated, value-based, and team-based medical care systems. In the future, pathologists will likely have to assume new roles, develop new expertise, and become more efficient in practicing medicine to accommodate new value-based delivery models. C1 [Robboy, Stanley J.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [Gupta, Saurabh] Smart Cube, Noida, India. [Crawford, James M.] North Shore Long Isl Jewish Hlth Syst, Dept Pathol & Lab Med, Manhasset, NY USA. [Cohen, Michael B.] Univ Utah, Dept Pathol, Huntsman Canc Hosp, Salt Lake City, UT USA. [Karcher, Donald S.] George Washington Univ, Dept Pathol, Washington, DC USA. [Leonard, Debra G. B.] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. [Magnani, Barbarajean] Tufts Univ, Sch Med, Dept Pathol, Boston, MA 02111 USA. [Novis, David A.] Novis Consulting, Lee, NH USA. [Prystowsky, Michael B.] Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10467 USA. [Prystowsky, Michael B.] Montefiore Med Ctr, Bronx, NY 10467 USA. [Powell, Suzanne Z.] Methodist Hosp, Dept Pathol & Genom Med, Houston, TX 77030 USA. [Gross, David J.] Coll Amer Pathologists, Policy Roundtable, Washington, DC USA. [Black-Schaffer, W. Stephen] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Black-Schaffer, W. Stephen] Harvard Univ, Sch Med, Boston, MA USA. RP Robboy, SJ (reprint author), Duke Univ, Med Ctr, Dept Pathol, Davison Bldg,Room 227M,DUMC 3712, Durham, NC 27710 USA. EM stanley.robboy@duke.edu NR 73 TC 0 Z9 0 U1 1 U2 1 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 NOV PY 2015 VL 139 IS 11 BP 1413 EP 1430 DI 10.5858/arpa.2014-0559-OA PG 18 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA DB3OT UT WOS:000368421700012 PM 26516939 ER PT J AU Norwitz, ER Bonney, EA Snegovskikh, VV Williams, MA Phillippe, M Park, JS Abrahams, VM AF Norwitz, Errol R. Bonney, Elizabeth A. Snegovskikh, Victoria V. Williams, Michelle A. Phillippe, Mark Park, Joong Shin Abrahams, Vikki M. TI Molecular Regulation of Parturition: The Role of the Decidual Clock SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID SPONTANEOUS PRETERM BIRTH; MATERNAL-FETAL INTERFACE; SEXUALLY-TRANSMITTED INFECTIONS; CORTICOTROPIN-RELEASING HORMONE; TOLL-LIKE RECEPTOR-4; T-CELL ACCESS; HUMAN-PREGNANCY; BACTERIAL VAGINOSIS; VIRAL-INFECTION; STROMAL CELLS AB The timing of birth is a critical determinant of perinatal outcome. Despite intensive research, the molecular mechanisms responsible for the onset of labor both at term and preterm remain unclear. It is likely that a "parturition cascade" exists that triggers labor at term, that preterm labor results from mechanisms that either prematurely stimulate or short-circuit this cascade, and that these mechanisms involve the activation of proinflammatory pathways within the uterus. It has long been postulated that the fetoplacental unit is in control of the timing of birth through a "placental clock." We suggest that it is not a placental clock that regulates the timing of birth, but rather a "decidual clock." Here, we review the evidence in support of the endometrium/decidua as the organ primarily responsible for the timing of birth and discuss the molecular mechanisms that prime this decidual clock. C1 [Norwitz, Errol R.] Tufts Med Ctr, Dept Obstet & Gynecol, Boston, MA 02111 USA. [Norwitz, Errol R.] Tufts Univ, Sch Med, Mother Infant Res Inst MIRI, Boston, MA 02110 USA. [Bonney, Elizabeth A.] Univ Vermont, Dept Obstet Gynecol & Reprod Sci, Burlington, VT 05405 USA. [Snegovskikh, Victoria V.] Women & Infants Hosp Rhode Isl, Dept Obstet & Gynecol, Div Reprod Endocrinol, Providence, RI 02905 USA. [Phillippe, Mark] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Phillippe, Mark] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. [Park, Joong Shin] Seoul Natl Univ, Coll Med, Dept Obstet & Gynecol, Seoul 110799, South Korea. [Abrahams, Vikki M.] Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, 333 Cedar St, New Haven, CT 06510 USA. RP Norwitz, ER (reprint author), Tufts Med Ctr, Dept Obstet & Gynecol, Boston, MA 02111 USA.; Norwitz, ER (reprint author), Tufts Univ, Sch Med, Mother Infant Res Inst MIRI, Boston, MA 02110 USA. EM enorwitz@tuftsmedicalcenter.org FU National Institutes of Health NIH/NICHD; March of Dimes Grants [21-FY05-1250, 21-FY06-574]; NIH/NICHD [RO1HD049446, PO1HD054713]; [P20 RR021905] FX This work was supported in part by the National Institutes of Health NIH/NICHD-sponsored Reproductive Scientist Development Program (to E.R.N.) and March of Dimes Grants (21-FY05-1250 to E.R.N. and 21-FY06-574 to E.A.B.). E.A.B. is also supported by a P20 RR021905 Grant to the Vermont Center for Immunology and Infectious Disease. V.M.A. is also supported by NIH/NICHD Grants (RO1HD049446 and PO1HD054713). NR 160 TC 1 Z9 1 U1 3 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 2157-1422 J9 CSH PERSPECT MED JI Cold Spring Harb. Perspect. Med. PD NOV PY 2015 VL 5 IS 11 AR a023143 DI 10.1101/cshperspect.a023143 PG 20 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DB6BL UT WOS:000368598000010 ER PT J AU Saha, D Ahmed, SS Rabkin, SD AF Saha, D. Ahmed, S. S. Rabkin, S. D. TI EXPLORING THE ANTITUMOR EFFECT OF VIRUS IN MALIGNANT GLIOMA SO DRUGS OF THE FUTURE LA English DT Review DE Oncolytic virus; Virotherapy; Glioblastoma; Glioma; Malignant neoplasms ID HERPES-SIMPLEX-VIRUS; VESICULAR STOMATITIS-VIRUS; RETROVIRAL REPLICATING VECTOR; LONG-TERM SURVIVAL; CANCER STEM-CELLS; PHASE-I TRIAL; INTERGENERIC POLIOVIRUS RECOMBINANTS; RECURRENT GLIOBLASTOMA-MULTIFORME; CONVECTION-ENHANCED DELIVERY; NEWCASTLE-DISEASE VIRUS AB Malignant gliomas are the most common type of primary malignant brain tumor with no effective treatments. Current conventional therapies (surgical resection, radiation therapy, temozolomide and bevacizumab administration) typically fail to eradicate the tumors resulting in the recurrence of treatment-resistant tumors. Therefore, novel approaches are needed to improve therapeutic outcomes. Oncolytic viruses (OVs) are excellent candidates as a more effective therapeutic strategy for aggressive cancers like malignant gliomas since OVs have a natural preference or have been genetically engineered to selectively replicate in and kill cancer cells. OVs have been used in numerous preclinical studies in malignant glioma, and a large number of clinical trials using OVs have been completed or are underway that have demonstrated safety, as well as provided indications of effective antiglioma activity. In this review, we will focus on those OVs that have been used in clinical trials for the treatment of malignant gliomas (herpes simplex virus, adenovirus, parvovirus, reovirus, poliovirus, Newcastle disease virus, measles virus and retrovirus) and OVs examined preclinically (vesicular stomatitis virus and myxoma virus), and describe how these agents are being used. C1 Massachusetts Gen Hosp, Brain Tumor Res Ctr, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Rabkin, SD (reprint author), Massachusetts Gen Hosp, Brain Tumor Res Ctr, 185 Cambridge St,CPZN 3800, Boston, MA 02114 USA. EM rabkin@mgh.harvard.edu FU National Cancer Institute; National Institutes of Neurological Disorders and Stroke; Thomas A. Pappas Chair in Neurosciences FX The authors thank past and current members of the laboratory for contributing to our research, which has been supported by grants from the National Cancer Institute, National Institutes of Neurological Disorders and Stroke, and the Thomas A. Pappas Chair in Neurosciences (to S.D. Rabkin). NR 139 TC 4 Z9 4 U1 7 U2 10 PU PROUS SCIENCE, SAU-THOMSON REUTERS PI BARCELONA PA 398 PROVENCA, 08025 BARCELONA, SPAIN SN 0377-8282 EI 2013-0368 J9 DRUG FUTURE JI Drug Future PD NOV PY 2015 VL 40 IS 11 BP 739 EP 749 DI 10.1358/dof.2015.040.11.2383070 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DB3MQ UT WOS:000368416100004 PM 26855472 ER PT J AU Lee, YJ Liu, CL Liao, MY Sukhova, GK Shirakawa, J Abdennour, M Iamarene, K Andre, S Inouye, K Clement, K Kulkarni, RN Banks, AS Libby, P Shi, GP AF Lee, Yun-Jung Liu, Conglin Liao, Mengyang Sukhova, Galina K. Shirakawa, Jun Abdennour, Meriem Iamarene, Karine Andre, Sebastien Inouye, Karen Clement, Karine Kulkarni, Rohit N. Banks, Alexander S. Libby, Peter Shi, Guo-Ping TI Deficiency of Fc epsilon R1 Increases Body Weight Gain but Improves Glucose Tolerance in Diet-Induced Obese Mice SO ENDOCRINOLOGY LA English DT Article ID MAST-CELLS; INSULIN-RESISTANCE; ADIPOCYTE DIFFERENTIATION; GUT INFLAMMATION; IMMUNOGLOBULIN-E; ADIPOSE-TISSUE; C/EBP-ALPHA; PPAR-GAMMA; T-CELLS; ASTHMA AB Prior studies demonstrated increased plasma IgE in diabetic patients, but the direct participation of IgE in diabetes or obesity remains unknown. This study found that plasma IgE levels correlated inversely with body weight, body mass index, and body fat mass among a population of randomly selected obese women. IgE receptor Fc is an element of R1-deficient (Fcer1a(-/-)) mice and diet-induced obesity (DIO) mice demonstrated that Fc is an element of R1 deficiency in DIO mice increased food intake, reduced energy expenditure, andincreased body weight gain but improved glucose tolerance an dglucose-induced insulin secretion. White adipose tissue from Fcer1a(-/-) mice showed an increased expression of phospho-AKT, CCAAT/enhancer binding protein-alpha, peroxisome proliferator-activated receptor-gamma, glucose transporter-4 (Glut4), and B-cell lymphoma 2 (Bcl2) but reduced uncoupling protein 1 (UCP1) and phosphorylated c-Jun N-terminal kinase (JNK) expression, tissue macrophage accumulation, and apoptosis, suggesting that IgE reduces adipogenesis and glucose uptake but induces energy expenditure, adipocyte apoptosis, and white adipose tissue inflammation. In 3T3-L1 cells, IgE inhibited the expression of CCAAT/enhancer binding protein-alpha and peroxisome proliferator activated receptor-gamma, and preadipocyte adipogenesis and induced adipocyte apoptosis. IgE reduced the 3T3-L1 cell expression of Glut4, phospho-AKT, and glucose uptake, which concurred with improved glucose tolerance in Fcer1a(-/-) mice. This study established two novel pathways of IgE in reducing body weight gain in DIO mice by suppressing adipogenesis and inducing adipocyte apoptosis while worsening glucose tolerance by reducing Glut4 expression, glucose uptake, and insulin secretion. C1 [Lee, Yun-Jung; Liu, Conglin; Liao, Mengyang; Sukhova, Galina K.; Iamarene, Karine; Banks, Alexander S.; Libby, Peter; Shi, Guo-Ping] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Iamarene, Karine] Harvard Univ, Sch Med, Dept Genet & Complex Dis, Boston, MA 02115 USA. [Shirakawa, Jun; Kulkarni, Rohit N.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Shirakawa, Jun; Kulkarni, Rohit N.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. [Liu, Conglin] Zhengzhou Univ, Affiliated Hosp 1, Dept Cardiol, Inst Clin Med, Zhengzhou 450003, Peoples R China. [Liao, Mengyang] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Inst Cardiol, Wuhan 430072, Peoples R China. [Abdennour, Meriem; Andre, Sebastien; Clement, Karine] Univ Paris 06, Inst Cardiometab & Nutr, NutriOm Team, INSERM,U1166,Unite Mixte Rech Sante, F-75013 Paris, France. [Abdennour, Meriem; Andre, Sebastien; Clement, Karine] Univ Paris 06, NutriOm Team, F-75013 Paris, France. RP Shi, GP (reprint author), Brigham & Womens Hosp, Dept Cardiovasc Med, 77 Ave Louis Pasteur,NRB-7, Boston, MA 02115 USA. EM gshi@rics.bwh.harvard.edu FU National Institutes of Health [HL60942, 1HL81090, 1HL88547, 1HL48743, 1HL080472, 1DK67536]; Programme Hospitalier de Recherche Clinique [0276]; Bar-Institute of Cardiometabolism and Nutrition project [1ANR-10-IAHU-05] FX This work was supported by National Institutes of Health Grants HL60942, zgn; 1HL81090, zgn; 1HL88547 (to G.-P.S.), zgn; 1HL48743, zgn; 1HL080472 (to P.L.), and zgn; 1DK67536 (to R.N.K.). The clinical work performed in France was supported by Programme Hospitalier de Recherche Clinique 0276 (adiposity signals, Ethical Agreement zgn; 1CPP No 1, Hotel-Dieu Hospital) and by Bar-Institute of Cardiometabolism and Nutrition project as part of Investment for the Future Grant zgn; 1ANR-10-IAHU-05. NR 46 TC 0 Z9 1 U1 1 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2015 VL 156 IS 11 BP 4047 EP 4058 DI 10.1210/en.2015-1184 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DB3JV UT WOS:000368408100019 PM 26295369 ER PT J AU Pei, PP Weinstein, MC Li, XC Hughes, MD Paltiel, AD Hou, T Parker, RA Gaynes, MR Sax, PE Freedberg, KA Schackman, BR Walensky, RP AF Pei, Pamela P. Weinstein, Milton C. Li, X. Cynthia Hughes, Michael D. Paltiel, A. David Hou, Taige Parker, Robert A. Gaynes, Melanie R. Sax, Paul E. Freedberg, Kenneth A. Schackman, Bruce R. Walensky, Rochelle P. TI Prioritizing HIV comparative effectiveness trials based on value of information: generic versus brand-name ART in the US SO HIV CLINICAL TRIALS LA English DT Article DE Value of information; HIV; Generic drugs; Cost-effectiveness analysis; Decision modeling ID COST-EFFECTIVENESS ANALYSIS; WILLINGNESS-TO-PAY; ADJUSTED LIFE-YEAR; MULTIPLE VIROLOGICAL FAILURES; ANTIRETROVIRAL-NAIVE ADULTS; ATAZANAVIR PLUS RITONAVIR; CARE RESOURCE-ALLOCATION; ONCE-DAILY DOLUTEGRAVIR; DOUBLE-BLIND; INITIAL TREATMENT AB Background: Value of Information (VOI) analysis examines whether to acquire information before making a decision. We introduced VOI to the HIV audience, using the example of generic antiretroviral therapy (ART) in the US. Methods and Findings: We used a mathematical model and probabilistic sensitivity analysis (PSA) to generate probability distributions of survival (in quality-adjusted life years, QALYs) and cost for three potential first-line ART regimens: three-pill generic, two-pill generic, and single-pill branded. These served as input for a comparison of two hypothetical two-arm trials: three-pill generic versus single-pill branded; and two-pill generic versus single-pill branded. We modeled pre-trial uncertainty by defining probability distributions around key inputs, including 24-week HIV-RNA suppression and subsequent ART failure. We assumed that, without a trial, patients received the single-pill branded strategy. Post-trial, we assumed that patients received the most cost-effective strategy. For both trials, we quantified the probability of changing to a generic-based regimen upon trial completion and the expected VOI in terms of improved health outcomes and costs. Assuming a willingness to pay (WTP) threshold of $100 000/QALY, the three-pill trial led to more treatment changes (84%) than the two-pill trial (78%). Estimated VOI was $48 000 (three-pill trial) and $35 700 (two-pill trial) per future patient initiating ART. Conclusions: A three-pill trial of generic ART is more likely to lead to post-trial treatment changes and to provide more value than a two-pill trial if policy decisions are based on cost-effectiveness. Value of Information analysis can identify trials likely to confer the greatest impact and value for HIV care. C1 [Pei, Pamela P.; Li, X. Cynthia; Hou, Taige; Parker, Robert A.; Gaynes, Melanie R.; Freedberg, Kenneth A.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Weinstein, Milton C.; Hughes, Michael D.; Freedberg, Kenneth A.] Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. [Weinstein, Milton C.; Parker, Robert A.; Sax, Paul E.; Freedberg, Kenneth A.; Walensky, Rochelle P.] Harvard Univ, Sch Med, Boston, MA USA. [Paltiel, A. David] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Parker, Robert A.] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA. [Sax, Paul E.; Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Schackman, Bruce R.] Weill Cornell Med Coll, Dept Healthcare Policy & Res, New York, NY USA. [Freedberg, Kenneth A.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Walensky, RP (reprint author), Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM rwalensky@partners.org FU National Institute of Allergy and Infectious Diseases of the National Institutes of Health [R01 AI093269, R37 AI42006] FX Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Numbers R01 AI093269 and R37 AI42006. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 1 Z9 1 U1 0 U2 1 PU MANEY PUBLISHING PI LEEDS PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND SN 1528-4336 EI 1945-5771 J9 HIV CLIN TRIALS JI HIV Clin. Trials PD NOV PY 2015 VL 16 IS 6 BP 207 EP 218 DI 10.1179/1945577115Y.0000000009 PG 12 WC Infectious Diseases; Pharmacology & Pharmacy SC Infectious Diseases; Pharmacology & Pharmacy GA DB7QM UT WOS:000368710700001 PM 26651525 ER PT J AU Calarge, CA Ziegler, EE Del Castillo, N Aman, M McDougle, CJ Scahill, L McCracken, JT Arnold, LE AF Calarge, Chadi A. Ziegler, Ekhard E. Del Castillo, Nicole Aman, Michael McDougle, Christopher J. Scahill, Lawrence McCracken, James T. Arnold, L. Eugene TI Iron Homeostasis During Risperidone Treatment in Children and Adolescents SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article DE Antipsychotics; Child and Adolescent Psychiatry ID PERVASIVE DEVELOPMENTAL DISORDERS; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT-HYPERACTIVITY DISORDER; DIAGNOSTIC INTERVIEW; FERRITIN; INFANTS; VERSION; SUPPLEMENTATION; INFLAMMATION; PREDICTORS AB Objective: Previous cross-sectional evidence has linked antipsychotic-related weight gain to reduced body iron concentration. Using longitudinal data, we examined the association between changes in weight following risperidone initiation or discontinuation and ferritin concentration. Method: Study 1: Between April 2004 and September 2007, participants were enrolled from outpatient settings in a prospective randomized clinical trial comparing the efficacy of risperidone monotherapy to the combination of risperidone and behavior therapy in targeting disruptive behavior in 4- to 13-year-old children with DSM-IV-TR-based autism spectrum disorder. Study 2: Medically healthy 7- to 17-year-old participants in long-term open-label risperidone treatment at study entry returned for follow-up 1.5 years later, between July 2007 and July 2011. Available blood samples were used to measure ferritin. Linear multivariable regression analysis tested the association between ferritin concentration and change in age-sex-specific body mass index (BMI) z score between study entry and endpoint, adjusting for relevant confounders. Results: Study 1 sample consisted of 73 participants (85% males, mean age: 7.7 +/- 2.4 years). After 18.0 +/- 2.0 weeks on risperidone, their BMI z score increased by 0.93 +/- 0.70 points and ferritin concentration declined by 6.8 +/- 13.3 mu g/L. After adjusting for age and sex, change in BMI z score was inversely correlated with percent change in ferritin concentration (beta = -18.3, P < .003). Study 2 participants had all been receiving risperidone at study entry. At follow-up, 1.5 +/- 0.3 years later, risperidone was discontinued in 26 of the 96 who were included in the analysis. Neither change in BMI z score nor in ferritin concentration was different between those who continued versus discontinued risperidone. However, a reduction in BMI z score between study entry and follow-up was associated with higher ferritin concentration at follow-up in participants who discontinued risperidone compared to those who continued it (P = .01). Conclusions: Risperidone-related weight gain is associated with a reduction in body iron reserves, which appears to improve with weight loss following risperidone discontinuation. Preliminary evidence suggests that risperidone may also directly inhibit iron absorption. (C) Copyright 2015 Physicians Postgraduate Press, Inc. C1 [Calarge, Chadi A.; Del Castillo, Nicole] Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA. [Calarge, Chadi A.; Ziegler, Ekhard E.] Univ Iowa, Dept Pediat, Carver Coll Med, Iowa City, IA 52242 USA. [Aman, Michael; Arnold, L. Eugene] Ohio State Univ, Dept Psychiat, Columbus, OH 43210 USA. [McDougle, Christopher J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat & Pediat, Cambridge, MA 02138 USA. [Scahill, Lawrence] Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA. [McCracken, James T.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. RP Calarge, CA (reprint author), Texas Childrens Hosp, Baylor Coll Med, 1102 Bates Ave,Suite 790, Houston, TX 77030 USA. EM chadi.calarge@bcm.edu FU NARSAD Young Investigator Award; National Institutes of Health [RR024979, R21MH080968, K23MH085005, U10MH66768] FX This study was funded by a 2005 and a 2007 NARSAD Young Investigator Award and by the National Institutes of Health (RR024979, R21MH080968, K23MH085005, and U10MH66768). NR 35 TC 2 Z9 2 U1 2 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD NOV PY 2015 VL 76 IS 11 BP 1500 EP 1505 DI 10.4088/JCP.14m09258 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DB2QF UT WOS:000368353400017 PM 26301448 ER PT J AU Wozniak, J Faraone, SV Chan, J Tarko, L Hernandez, M Davis, J Woodworth, KY Biederman, J AF Wozniak, Janet Faraone, Stephen V. Chan, James Tarko, Laura Hernandez, Mariely Davis, Jacqueline Woodworth, K. Yvonne Biederman, Joseph TI A Randomized Clinical Trial of High Eicosapentaenoic Acid Omega-3 Fatty Acids and Inositol as Monotherapy and in Combination in the Treatment of Pediatric Bipolar Spectrum Disorders: A Pilot Study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article DE Bipolar Disorder; Child and Adolescent Psychiatry; Complementary and Alternative Medicines ID RATING-SCALE; DEPRESSIVE DISORDER; MYOINOSITOL LEVELS; LITHIUM TREATMENT; CHILDREN; ADOLESCENTS; CHILDHOOD; RESONANCE; AUGMENTATION; SPECTROSCOPY AB Objective: We conducted a 12-week, randomized, double-blind, controlled clinical trial to evaluate the effectiveness and tolerability of high eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) omega-3 fatty acids and inositol as monotherapy and in combination in children with bipolar spectrum disorders. Method: Participants were children 5-12 years of age meeting DSM-IV diagnostic criteria for bipolar spectrum disorders (bipolar I or II disorder or bipolar disorder not otherwise specified [NOS]) and displaying mixed, manic, or hypomanic symptoms. Subjects with severe illness were excluded. Subjects were randomized to 1 of 3 treatment arms: inositol plus placebo, omega-3 fatty acids plus placebo, and the combined active treatment of omega-3 fatty acids plus inositol. Data were collected from February 2012 to November 2013. Results: Twenty-four subjects were exposed to treatment (>= 1 week of study completed) (inositol [n = 7], omega-3 fatty acids [n = 7], and omega-3 fatty acids plus inositol [n = 10]). Fifty-four percent of the subjects completed the study. Subjects randomized to the omega-3 fatty acids plus inositol arm had the largest score decrease comparing improvement from baseline to end point with respect to the Young Mania Rating Scale (P < .05). Similar results were found for the Children's Depression Rating Scale (P < .05) and the Brief Psychiatric Rating Scale (P < .05). Conclusions: Results of this pilot randomized, double-blind, controlled trial suggest that the combined treatment of omega-3 fatty acids plus inositol reduced symptoms of mania and depression in prepubertal children with mild to moderate bipolar spectrum disorders. Results should be interpreted in light of limitations, which include exclusion of severely ill subjects, 54% completion rate, and small sample size. (C) Copyright 2015 Physicians Postgraduate Press, Inc. C1 [Wozniak, Janet; Chan, James; Tarko, Laura; Hernandez, Mariely; Davis, Jacqueline; Woodworth, K. Yvonne; Biederman, Joseph] Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. [Wozniak, Janet; Biederman, Joseph] Harvard Univ, Sch Med, Boston, MA USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, 55 Fruit St YAW 6A, Boston, MA 02114 USA. EM jbiederman@partners.org FU Cantor Colburn; Merck; UCB; Xenoport; UCB Pharma; Purdue; NeuroMetrix; Pfizer; Ironshore; Shire; Akili Interactive Laboratories; Alcobra; VAYA Pharma; Neurovance; National Institutes of Health (NIH); Otsuka; McNeil; Janssen; Novartis; Eli Lilly; Department of Defense; Vaya Pharma/Enzymotec; NIH; Massachusetts General Hospital (MGH) Psychiatry Academy; Ingenix; Prophase; Bracket Global Sunovion; Theravance; APSARD; ElMindA; MGH Psychiatry Academy FX From 2014 to 2015, Dr Wozniak received no outside income or research support. She is the author of the book Is Your Child Bipolar, published May 2008, Bantam Books. From 2014 to 2015, her spouse, John Winkelman, MD, PhD, received royalties from Cambridge University Press and UptoDate; received consultation fees from Cantor Colburn, Merck, UCB, and Xenoport; and received research support from UCB Pharma, Purdue, and NeuroMetrix. In the past year, Dr Faraone received income, travel expenses, and/or research support from Pfizer, Ironshore, Shire, Akili Interactive Laboratories, Alcobra, VAYA Pharma, and Neurovance and research support from the National Institutes of Health (NIH). His institution is seeking a patent for the use of sodium-hydrogen exchange inhibitors in the treatment of attention-deficit/hyperactivity disorder (ADHD). In previous years, he received consulting fees or was on advisory boards or participated in continuing medical education programs sponsored by Shire, Alcobra, Otsuka, McNeil, Janssen, Novartis, Pfizer, and Eli Lilly. He receives royalties from books published by Guilford Press, Straight Talk about Your Child's Mental Health, and Oxford University Press, Schizophrenia: The Facts. Dr Biederman is currently receiving research support from the Department of Defense, Ironshore, Vaya Pharma/Enzymotec, and NIH. In 2014, he received honoraria from the Massachusetts General Hospital (MGH) Psychiatry Academy for tuition-funded CME courses. He has a US patent application pending (provisional number #61/233,686) through MGH corporate licensing on a method to prevent stimulant abuse. He received departmental royalties from a copyrighted rating scale used for ADHD diagnoses, paid to the Department of Psychiatry at MGH by Ingenix, Prophase, Shire, Bracket Global Sunovion, and Theravance. In 2013, he received an honorarium from the MGH Psychiatry Academy for a tuition-funded CME course. He received research support from APSARD, ElMindA, McNeil, and Shire. He received departmental royalties from a copyrighted rating scale used for ADHD diagnoses, paid to the Department of Psychiatry at MGH by Shire and Sunovion. Mr Chan and Mss Tarko, Hernandez, Davis, and Woodworth report no financial or other relationship relevant to the subject of this article. NR 32 TC 1 Z9 1 U1 6 U2 8 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD NOV PY 2015 VL 76 IS 11 BP 1548 EP 1555 DI 10.4088/JCP.14m09267 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA DB2QF UT WOS:000368353400024 PM 26646031 ER PT J AU Ho, AK Thorpe, CT Pandhi, N Palta, M Smith, MA Johnson, HM AF Ho, Aaron K. Thorpe, Carolyn T. Pandhi, Nancy Palta, Mari Smith, Maureen A. Johnson, Heather M. TI Association of anxiety and depression with hypertension control: a US multidisciplinary group practice observational study SO JOURNAL OF HYPERTENSION LA English DT Article DE anxiety; depression; diagnosis; hypertension; Kaplan-Meier estimate; retrospective studies; United States ID HEALTH-CARE UTILIZATION; MIDDLE-AGED MEN; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; GENERALIZED ANXIETY; CLINICAL INERTIA; UNITED-STATES; YOUNG-ADULTS; RISK-FACTOR; DISORDERS AB Objective:The presence of a mental health disorder with hypertension is associated with higher cardiovascular disease mortality than hypertension alone. Although earlier detection of hypertension has been demonstrated in patients with anxiety and depression, the relationship of mental health disorders to hypertension control is unknown. Our objective was to evaluate rates and predictors of incident hypertension control among patients with anxiety and/or depression compared with patients without either mental health diagnosis.Methods:A 4-year retrospective analysis included 4362 patients, at least 18 years old, who received primary care in a large academic group practice from 2008 to 2011. Patients met The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure criteria and had a hypertension diagnosis. Kaplan-Meier analysis estimated the probability of achieving control for patients with and without anxiety and/or depression. Cox proportional hazard models were fit to identify predictors of time to control.Results:Overall, 13% (n=573) had a baseline diagnosis of anxiety and/or depression. Those with anxiety and/or depression demonstrated more primary care and specialty visits than those without either condition. After adjustment, patients with anxiety and/or depression had faster rates of hypertension control (hazard ratio [HR] 1.22; 1.07-1.39] than patients without either diagnosis. Other associations of faster hypertension control included female gender (HR 1.32; 1.20-1.44), absence of tobacco use (HR 1.17; 1.03-1.33), Medicaid use (HR 1.27; 1.09-1.49), and a higher Adjusted Clinical Group Risk Score (HR 1.13; 1.10-1.17), a measure of healthcare utilization.Conclusion:Greater healthcare utilization among patients with anxiety and/or depression may contribute to faster hypertension control. C1 [Ho, Aaron K.; Johnson, Heather M.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA. [Thorpe, Carolyn T.] Univ Pittsburgh, Ctr Hlth Equ Res & Promot, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Thorpe, Carolyn T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [Pandhi, Nancy; Smith, Maureen A.; Johnson, Heather M.] Univ Wisconsin, Sch Med & Publ Hlth, Hlth Innovat Program, Madison, WI USA. [Pandhi, Nancy; Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Family Med, Madison, WI USA. [Palta, Mari; Smith, Maureen A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA. [Palta, Mari] Univ Wisconsin, Sch Med & Publ Hlth, Dept Biostat & Med Informat, Madison, WI USA. [Smith, Maureen A.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI USA. RP Johnson, HM (reprint author), Div Cardiovasc Med, H4-512 CSC,MC 3248,600 Highland Ave, Madison, WI 53792 USA. EM hm2@medicine.wisc.edu FU Clinical and Translational Science Award program [NCRR - UL1RR025011]; National Center for Advancing Translational Sciences of the National Institutes of Health (N.I.H.) [UL1TR000427]; National Heart, Lung, and Blood Institute of the NIH [K23HL112907]; University of Wisconsin Centennial Scholars Program of the University of Wisconsin School of Medicine and Public Health; National Institute on Aging of the N.I.H [K08AG029527]; University of Wisconsin Health Innovation Program; University of Wisconsin School of Medicine and Public Health from The Wisconsin Partnership Program FX This original research was supported by the Clinical and Translational Science Award program, previously through the National Center for Research Resources (NCRR - UL1RR025011), and now by the National Center for Advancing Translational Sciences of the National Institutes of Health (N.I.H.) under award number UL1TR000427. H.M.J. is supported by the National Heart, Lung, and Blood Institute of the NIH (K23HL112907), and also by the University of Wisconsin Centennial Scholars Program of the University of Wisconsin School of Medicine and Public Health. N.P. is supported by the National Institute on Aging of the N.I.H. (K08AG029527). The content is solely the responsibility of the authors and does not necessarily represent the official views of the N.I.H.; Additional funding for this project was provided by the University of Wisconsin Health Innovation Program and the University of Wisconsin School of Medicine and Public Health from The Wisconsin Partnership Program. NR 41 TC 3 Z9 4 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0263-6352 EI 1473-5598 J9 J HYPERTENS JI J. Hypertens. PD NOV PY 2015 VL 33 IS 11 BP 2215 EP 2222 DI 10.1097/HJH.0000000000000693 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA DB4OE UT WOS:000368491800008 PM 26259121 ER PT J AU Chadwick, EJ Yang, DP Filbin, MG Mazzola, E Sun, Y Behar, O Pazyra-Murphy, MF Goumnerova, L Ligon, KL Stiles, CD Segal, RA AF Chadwick, Emily J. Yang, David P. Filbin, Mariella G. Mazzola, Emanuele Sun, Yu Behar, Oded Pazyra-Murphy, Maria F. Goumnerova, Liliana Ligon, Keith L. Stiles, Charles D. Segal, Rosalind A. TI A Brain Tumor/Organotypic Slice Co-culture System for Studying Tumor Microenvironment and Targeted Drug Therapies SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Medicine; Issue 105; Tumor; Brain; Microenvironment; Treatment; Mouse; Astrocytoma; Slice; Co-Culture ID CELLS AB Brain tumors are a major cause of cancer-related morbidity and mortality. Developing new therapeutics for these cancers is difficult, as many of these tumors are not easily grown in standard culture conditions. Neurosphere cultures under serum-free conditions and orthotopic xenografts have expanded the range of tumors that can be maintained. However, many types of brain tumors remain difficult to propagate or study. This is particularly true for pediatric brain tumors such as pilocytic astrocytomas and medulloblastomas. This protocol describes a system that allows primary human brain tumors to be grown in culture. This quantitative assay can be used to investigate the effect of microenvironment on tumor growth, and to test new drug therapies. This protocol describes a system where fluorescently labeled brain tumor cells are grown on an organotypic brain slice from a juvenile mouse. The response of tumor cells to drug treatments can be studied in this assay, by analyzing changes in the number of cells on the slice over time. In addition, this system can address the nature of the microenvironment that normally fosters growth of brain tumors. This brain tumor organotypic slice co-culture assay provides a propitious system for testing new drugs on human tumor cells within a brain microenvironment. C1 [Chadwick, Emily J.; Yang, David P.; Sun, Yu; Behar, Oded; Pazyra-Murphy, Maria F.; Stiles, Charles D.; Segal, Rosalind A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. [Filbin, Mariella G.] Childrens Hosp, Dept Pediat, Boston, MA 02215 USA. [Mazzola, Emanuele] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Behar, Oded] Hebrew Univ Jerusalem, Dept Dev Biol & Canc Res, IL-91905 Jerusalem, Israel. [Goumnerova, Liliana] Childrens Hosp, Dept Neurosurg, Boston, MA 02215 USA. [Ligon, Keith L.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Mol Oncol Pathol, Boston, MA 02215 USA. RP Segal, RA (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA. EM rosalind_segal@dfci.harvard.edu FU NIH [P01CA142536, T32CA009361]; Pediatric Low Grade Astrocytoma foundation FX This work is supported by grants from the NIH (P01CA142536 to RAS, T32CA009361 to DPY) and the Pediatric Low Grade Astrocytoma foundation. NR 11 TC 0 Z9 0 U1 2 U2 3 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD NOV PY 2015 IS 105 AR e53304 DI 10.3791/53304 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB5SM UT WOS:000368573900053 PM 26575352 ER PT J AU Chao, W Kolski-Andreaco, A AF Chao, Wendy Kolski-Andreaco, Aaron TI November 2015: This Month in JoVE SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE This Month in JoVE; Issue 105 AB Here's a look at what's coming up in the November 2015 issue of JoVE: The Journal of Visualized Experiments. In JoVE Neuroscience, we know that fruit flies (Drosophila melanogaster) are a lot like humans in many ways-especially because they like their personal space. And in fruit flies, this preferred social distance can be measured using the social space assay. McNiel et al. demonstrate this straightforward protocol, which requires only simple equipment and experimental setups. Flies are blown into a social chamber and forced to form a tight group. Then they're allowed to take their preferred distance from one another. These distances are measured and processed with free online software (ImageJ). This social space assay provides a simple yet powerful paradigm for analyzing the underlying neurogenetics and environmental factors of social behavior. In JoVE Behavior, humans have a natural ability to acquire new motor skills, and this ability is crucial for upper limb amputees as they learn the complex control schemes for advanced multifunctional prosthetics. This month, Roche et al. present a case study of a structured rehabilitation method, which aims to improve multifunctional prosthetic control. Their subject underwent a structured protocol of imitation, repetition, and reinforcement learning. The subject demonstrated improvement in a widely used hand function test. This study suggests that a structured rehabilitation method may facilitate proficiency for multifunctional prosthetic control, and provides basis for larger clinical studies. Stress is a major concept in JoVE Behavior, and comprises various physiological responses to challenges. Among other responses, stress increases body temperature, which provides a quantitative measure of this response. However, the very act of measuring body temperature can be stressful to subjects, especially if they're wild animals. So Jerem et al. present a protocol for noninvasively measuring temperature in wild birds using infrared thermography. Their set-up is equipped with bird food and an infrared camera. This takes a thermal video of the bird before and after the researcher remotely closes the box, which acts as a mild acute stressor. The skin around the bird's eye is the warmest area in the image, and this protocol provides a time series of eye-region temperature with fine temporal resolution. With further validation, this method may prove valuable for studying the dynamics of the stress response for a wide range of researchers from environmental science to medicine. You've just had a sneak peek of the November 2015 issue of JoVE. Visit the website to see the full-length articles, plus many more, in JoVE: The Journal of Visualized Experiments. C1 [Chao, Wendy] Massachusetts Eye & Ear, Dept Ophthalmol, Boston, MA 02114 USA. [Chao, Wendy; Kolski-Andreaco, Aaron] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Kolski-Andreaco, Aaron] JoVE Content Prod, Boston, MA USA. RP Kolski-Andreaco, A (reprint author), JoVE Content Prod, Boston, MA USA. EM aaron.kolski-andreaco@jove.com NR 0 TC 0 Z9 0 U1 1 U2 3 PU JOURNAL OF VISUALIZED EXPERIMENTS PI CAMBRIDGE PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA SN 1940-087X J9 JOVE-J VIS EXP JI J. Vis. Exp. PD NOV PY 2015 IS 105 AR e5758 DI 10.3791/5758 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DB5SM UT WOS:000368573900072 ER PT J AU Levin, VA Tonge, PJ Gallo, JM Birtwistle, MR Dar, AC Iavarone, A Paddison, PJ Heffron, TP Elmquist, WF Lachowicz, JE Johnson, TW White, FM Sul, J Smith, QR Shen, W Sarkaria, JN Samala, R Wen, PY Berry, DA Petter, RC AF Levin, Victor A. Tonge, Peter J. Gallo, James M. Birtwistle, Marc R. Dar, Arvin C. Iavarone, Antonio Paddison, Patrick J. Heffron, Timothy P. Elmquist, William F. Lachowicz, Jean E. Johnson, Ted W. White, Forest M. Sul, Joohee Smith, Quentin R. Shen, Wang Sarkaria, Jann N. Samala, Ramakrishna Wen, Patrick Y. Berry, Donald A. Petter, Russell C. TI CNS Anticancer Drug Discovery and Development Conference White Paper SO NEURO-ONCOLOGY LA English DT Article DE brain metastasis; chemotherapy; glioma; medulloblastoma; pharmacokinetics; pharmacology ID PHASE-II TRIAL; RECURRENT GLIOBLASTOMA-MULTIFORME; BRAIN-TUMOR CONSORTIUM; CENTRAL-NERVOUS-SYSTEM; HIGH-DOSE METHOTREXATE; CANCER-TREATMENT GROUP; HIGH-GRADE GLIOMAS; FRACTIONATION RADIATION-THERAPY; RADIOTHERAPY PLUS PROCARBAZINE; PROGRESSION-FREE SURVIVAL AB Following the first CNS Anticancer Drug Discovery and Development Conference, the speakers from the first 4 sessions and organizers of the conference created this White Paper hoping to stimulate more and better CNS anticancer drug discovery and development. The first part of the White Paper reviews, comments, and, in some cases, expands on the 4 session areas critical to new drug development: pharmacological challenges, recent drug approaches, drug targets and discovery, and clinical paths. Following this concise review of the science and clinical aspects of new CNS anticancer drug discovery and development, we discuss, under the rubric "Accelerating Drug Discovery and Development for Brain Tumors," further reasons why the pharmaceutical industry and academia have failed to develop new anticancer drugs for CNS malignancies and what it will take to change the current status quo and develop the drugs so desperately needed by our patients with malignant CNS tumors. While this White Paper is not a formal roadmap to that end, it should be an educational guide to clinicians and scientists to help move a stagnant field forward. C1 [Levin, Victor A.] Kaiser Permanente, Redwood City, CA USA. [Levin, Victor A.; Berry, Donald A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Levin, Victor A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Tonge, Peter J.] SUNY Stony Brook, Stony Brook, NY 11794 USA. [Gallo, James M.; Birtwistle, Marc R.; Dar, Arvin C.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Iavarone, Antonio] Columbia Univ, Inst Canc Genet, New York, NY USA. [Paddison, Patrick J.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Heffron, Timothy P.] Genentech Inc, San Francisco, CA 94080 USA. [Elmquist, William F.] Univ Minnesota, Sch Pharm, Minneapolis, MN USA. [Lachowicz, Jean E.] Angiochem Inc, Montreal, PQ, Canada. [Johnson, Ted W.] Pfizer Oncol, San Diego, CA USA. [White, Forest M.] MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Sul, Joohee] US FDA, Silver Spring, MD USA. [Smith, Quentin R.; Samala, Ramakrishna] Texas Tech Univ, Sch Pharm, Amarillo, TX USA. [Shen, Wang] NewGen Therapeut Inc, Menlo Pk, CA USA. [Sarkaria, Jann N.] Mayo Clin, Rochester, MN USA. [Wen, Patrick Y.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Petter, Russell C.] Celgene Avil Res, Bedford, MA USA. RP Levin, VA (reprint author), Kaiser Permanente, Redwood City, CA USA. EM vlevin11@gmail.com FU Genentech; American Brain Tumor Association; Society for Neuro-Oncology; Bristol-Myers Squibb; Celgene; Novartis FX This manuscript was the product of the first CNS Anticancer Drug Discovery and Development Conference, which was supported by Genentech (a member of the Roche Group), the American Brain Tumor Association, the Society for Neuro-Oncology, Bristol-Myers Squibb, Celgene, and Novartis. NR 201 TC 3 Z9 3 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2015 VL 17 SU 6 BP 1 EP 26 DI 10.1093/neuonc/nov169 PG 26 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DB3OH UT WOS:000368420500001 ER PT J AU Curry, WT Lim, M AF Curry, William T. Lim, Michael TI Immunomodulation: checkpoint blockade etc. SO NEURO-ONCOLOGY LA English DT Article DE biomarker; checkpoint blockade; clinical trial; glioblastoma; immunotherapy ID CELL LUNG-CANCER; CTLA-4 BLOCKADE; MONOCLONAL-ANTIBODIES; IPILIMUMAB; MELANOMA; RADIATION; KINETICS; PD-1; IMMUNOTHERAPY; PEMBROLIZUMAB AB The immune microenvironment is considered a major obstacle to generating an effective antitumor immune response. Checkpoint inhibitors manipulate the co-stimulatory response between antigen-presenting cells and immune cells-or between the tumor and immune cells-to elicit an antitumor immune response that would have otherwise been suppressed. Checkpoint inhibitors have shown great promise in the clinics, and some inhibitors such as anti-CTLA-4 antibodies and anti-PD-1 antibodies have gained FDA approval for certain tumors. Here we will discuss the current state of checkpoint inhibitors, biomarker strategies, and management of associated toxicities in glioblastoma. C1 [Curry, William T.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. [Curry, William T.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Lim, Michael] Johns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD 21287 USA. RP Lim, M (reprint author), Johns Hopkins Univ, Sch Med, 600 North Wolfe St,Phipps Bldg Rm 123, Baltimore, MD 21287 USA. EM mlim3@jhmi.edu NR 34 TC 5 Z9 5 U1 3 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2015 VL 17 SU 7 BP 26 EP 31 DI 10.1093/neuonc/nov174 PG 6 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DB3OO UT WOS:000368421200006 PM 26516223 ER PT J AU Reardon, DA Gilbert, MR Wick, W Liau, LD AF Reardon, David A. Gilbert, Mark R. Wick, Wolfgang Liau, Linda TI Immunotherapy for neuro-oncology: the critical rationale for combinatorial therapy SO NEURO-ONCOLOGY LA English DT Article DE glioblastoma; immunotherapy; immune checkpoint; programmed-death 1; vaccine ID REGULATORY T-CELLS; ENDOTHELIAL GROWTH-FACTOR; ANTITUMOR IMMUNE-RESPONSES; PULSED DENDRITIC CELLS; LYMPHOCYTE-ASSOCIATED ANTIGEN-4; TUMOR-INFILTRATING LYMPHOCYTES; HUMAN GLIOBLASTOMA-MULTIFORME; NEWLY-DIAGNOSED GLIOBLASTOMA; CANCER-IMMUNOTHERAPY; SUPPRESSOR-CELLS AB A successful therapeutic paradigm established historically in oncology involves combining agents with potentially complementary mechanisms of antitumor activity into rationally designed regimens. For example, cocktails of cytotoxic agents, which were carefully designed based on mechanisms of action, dose, and scheduling considerations, have led to dramatic improvements in survival including cures for childhood leukemia, Hodgkin's lymphoma, and several other complex cancers. Outcome for glioblastoma, the most common primary malignant CNS cancer, has been more modest, but nonetheless our current standard of care derives from confirmation that combination therapy surpasses single modality therapy. Immunotherapy has recently come of age for medical oncology with exciting therapeutic benefits achieved by several types of agents including vaccines, adoptive T cells, and immune checkpoint inhibitors against several types of cancers. Nonetheless, most benefits are relatively short, while others are durable but are limited to a minority of treated patients. Critical factors limiting efficacy of immunotherapeutics include insufficient immunogenicity and/or inadequate ability to overcome immunosuppressive factors exploited by tumors. The paradigm of rationally designed combinatorial regimens, originally established by cytotoxic therapy for oncology, may also prove relevant for immunotherapy. Realization of the true therapeutic potential of immunotherapy for medical oncology and neuro-oncology patients may require development of combinatorial regimens that optimize immunogenicity and target tumor adaptive immunosuppressive factors. C1 [Reardon, David A.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. [Reardon, David A.] Dana Farber Brigham & Womens Canc Ctr, Dept Med Oncol, Boston, MA USA. [Gilbert, Mark R.] NCI, Neurol Clin, Bethesda, MD 20892 USA. [Gilbert, Mark R.] NCI, Natl Ctr Canc Res, Bethesda, MD 20892 USA. [Wick, Wolfgang] Heidelberg Univ, Neurol Clin, Heidelberg, Germany. [Wick, Wolfgang] Heidelberg Univ, Natl Ctr Tumor Dis, Heidelberg, Germany. [Wick, Wolfgang] German Canc Res Ctr, German Consortium Translat Canc Res DKTK, Heidelberg, Germany. [Liau, Linda] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurosurg, Brain Tumor Program, Los Angeles, CA 90095 USA. RP Reardon, DA (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, 450 Brookline Ave,D2134, Boston, MA 02215 USA. EM david_reardon@dfci.harvard.edu RI Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 FU Celldex Pharmaceuticals; Incyte, Inc.; GlaxoSmithKline; Genentech; Apogenix [APG101]; Boehringer Ingelheim; Eli Lilly; immatics; MSD; Roche; Northwest Biotherapeutics, Inc. FX David A. Reardon, MD, has served as a speakers' bureau member for Merck and Genentech/Roche and has received research support from Celldex Pharmaceuticals and Incyte, Inc. He has also served on advisory boards for Abbvie, Amgen, Cavion, EMD Serono, Genentech/Roche, Merck, Midatech, Momenta Pharmaceuticals, Novocure, Novartis, Regeneron, and Stemline Therapeutics.; Mark R. Gilbert, MD, has served on advisory boards for Abbvie, EMD Serono, Genentech/Roche, Merck, and Cell Medica. He has received research support from GlaxoSmithKline and Genentech.; Wolfgang Wick, MD, has received research grants from Apogenix, Boehringer Ingelheim, Eli Lilly, immatics, MSD, and Roche as well as honoraria for lectures or advisory board participation from MSD and Roche. He is or has been the coordinating investigator for sponsored clinical trials evaluating APG101 (Apogenix), bevacizumab (Roche), galunisertib (Eli Lilly), temozolomide (MSD), and temsirolimus (Pfizer).; Linda Liau, MD, PhD, has received research funding from Northwest Biotherapeutics, Inc. NR 133 TC 3 Z9 3 U1 2 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD NOV PY 2015 VL 17 SU 7 BP 32 EP 40 DI 10.1093/neuonc/nov178 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA DB3OO UT WOS:000368421200007 PM 26516225 ER PT J AU Tseng, CW Biancotti, JC Berg, BL Gate, D Kolar, SL Muller, S Rodriguez, MD Rezai-Zadeh, K Fan, XM Beenhouwer, DO Town, T Liu, GY AF Tseng, Ching Wen Biancotti, Juan Carlos Berg, Bethany L. Gate, David Kolar, Stacey L. Mueller, Sabrina Rodriguez, Maria D. Rezai-Zadeh, Kavon Fan, Xuemo Beenhouwer, David O. Town, Terrence Liu, George Y. TI Increased Susceptibility of Humanized NSG Mice to Panton-Valentine Leukocidin and Staphylococcus aureus Skin Infection SO PLOS PATHOGENS LA English DT Article ID SCID IL2R-GAMMA(NULL) MICE; HUMAN C5A RECEPTORS; TOXINS; INFLAMMATION; SPECIFICITY; ANTAGONISTS; INJURY; MODEL; CB AB Staphylococcus aureus is a leading cause of skin and soft-tissue infections worldwide. Mice are the most commonly used animals for modeling human staphylococcal infections. However a supra-physiologic S. aureus inoculum is required to establish gross murine skin pathology. Moreover, many staphylococcal factors, including Panton-Valentine leukocidin (PVL) elaborated by community-associated methicillin-resistant S. aureus (CA-MRSA), exhibit selective human tropism and cannot be adequately studied in mice. To overcome these deficiencies, we investigated S. aureus infection in non-obese diabetic (NOD)/severe combined immune deficiency (SCID)/IL2r gamma(null) (NSG) mice engrafted with human CD34(+) umbilical cord blood cells. These "humanized" NSG mice require one to two log lower inoculum to induce consistent skin lesions compared with control mice, and exhibit larger cutaneous lesions upon infection with PVL+ versus isogenic PVL-S. aureus. Neutrophils appear important for PVL pathology as adoptive transfer of human neutrophils alone to NSG mice was sufficient to induce dermonecrosis following challenge with PVL+ S. aureus but not PVL-S. aureus. PMX53, a human C5aR inhibitor, blocked PVL-induced cellular cytotoxicity in vitro and reduced the size difference of lesions induced by the PVL+ and PVL-S. aureus, but PMX53 also reduced recruitment of neutrophils and exacerbated the infection. Overall, our findings establish humanized mice as an important translational tool for the study of S. aureus infection and provide strong evidence that PVL is a human virulence factor. C1 [Tseng, Ching Wen; Berg, Bethany L.; Kolar, Stacey L.; Mueller, Sabrina; Rodriguez, Maria D.; Liu, George Y.] Cedars Sinai Med Ctr, Div Pediat Infect Dis, Los Angeles, CA 90048 USA. [Tseng, Ching Wen; Berg, Bethany L.; Kolar, Stacey L.; Mueller, Sabrina; Rodriguez, Maria D.; Liu, George Y.] Cedars Sinai Med Ctr, Immunobiol Res Inst, Los Angeles, CA 90048 USA. [Tseng, Ching Wen; Berg, Bethany L.; Kolar, Stacey L.; Mueller, Sabrina; Rodriguez, Maria D.; Liu, George Y.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. [Biancotti, Juan Carlos; Gate, David; Town, Terrence] Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Zilkha Neurogenet Inst, Los Angeles, CA 90033 USA. [Gate, David; Rezai-Zadeh, Kavon] Cedars Sinai Med Ctr, Dept Biomed Sci, Los Angeles, CA 90048 USA. [Fan, Xuemo] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. [Beenhouwer, David O.] Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA USA. [Beenhouwer, David O.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Tseng, CW (reprint author), Cedars Sinai Med Ctr, Div Pediat Infect Dis, Los Angeles, CA 90048 USA. EM dolorsas@gmail.com; George.Liu@cshs.org FU US National Institutes of Health [R01: AI074832]; California Institute for Regenerative Medicine [RM1-01735] FX This work was supported by a grant from a US National Institutes of Health to GYL (R01: AI074832) and a grant from the California Institute for Regenerative Medicine to TT. (RM1-01735). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 35 TC 3 Z9 3 U1 1 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD NOV PY 2015 VL 11 IS 11 AR e1005292 DI 10.1371/journal.ppat.1005292 PG 17 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA DB2IR UT WOS:000368332000039 PM 26618545 ER PT J AU McLoud, TC AF McLoud, Theresa C. TI Invited Commentary on "American Thoracic Society-European Respiratory Society Classification of the Idiopathic Interstitial Pneumonias" SO RADIOGRAPHICS LA English DT Editorial Material ID INFILTRATIVE LUNG-DISEASE; PULMONARY-FIBROSIS; EMPHYSEMA; CT; SURVIVAL C1 [McLoud, Theresa C.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP McLoud, TC (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 14 TC 0 Z9 0 U1 1 U2 1 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 NOV-DEC PY 2015 VL 35 IS 7 BP 1872 EP 1873 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DB2MX UT WOS:000368344100002 ER PT J AU Fintelmann, FJ Bernheim, A Digumarthy, SR Lennes, IT Kalra, MK Gilman, MD Sharma, A Flores, EJ Muse, VV Shepard, JAO AF Fintelmann, Florian J. Bernheim, Adam Digumarthy, Subba R. Lennes, Inga T. Kalra, Mannudeep K. Gilman, Matthew D. Sharma, Amita Flores, Efren J. Muse, Victorine V. Shepard, Jo-Anne O. TI The 10 Pillars of Lung Cancer Screening: Rationale and Logistics of a Lung Cancer Screening Program SO RADIOGRAPHICS LA English DT Article ID COMPUTED-TOMOGRAPHY SCANS; PULMONARY NODULES; CT; VARIABILITY; TRIAL; PROBABILITY; PERFORMANCE; STATEMENT; DECISION; ISSUES AB On the basis of the National Lung Screening Trial data released in 2011, the U.S. Preventive Services Task Force made lung cancer screening (LCS) with low-dose computed tomography (CT) a public health recommendation in 2013. The Centers for Medicare and Medicaid Services (CMS) currently reimburse LCS for asymptomatic individuals aged 55-77 years who have a tobacco smoking history of at least 30 pack-years and who are either currently smoking or had quit less than 15 years earlier. Commercial insurers reimburse the cost of LCS for individuals aged 55-80 years with the same smoking history. Effective care for the millions of Americans who qualify for LCS requires an organized step-wise approach. The 10-pillar model reflects the elements required to support a successful LCS program: eligibility, education, examination ordering, image acquisition, image review, communication, referral network, quality improvement, reimbursement, and research frontiers. Examination ordering can be coupled with decision support to ensure that only eligible individuals undergo LCS. Communication of results revolves around the Lung Imaging Reporting and Data System (Lung-RADS) from the American College of Radiology. Lung-RADS is a structured decision-oriented reporting system designed to minimize the rate of false-positive screening examination results. With nodule size and morphology as discriminators, Lung-RADS links nodule management pathways to the variety of nodules present on LCS CT studies. Tracking of patient outcomes is facilitated by a CMS-approved national registry maintained by the American College of Radiology. (C) RSNA, 2015 C1 [Fintelmann, Florian J.; Bernheim, Adam; Digumarthy, Subba R.; Kalra, Mannudeep K.; Gilman, Matthew D.; Sharma, Amita; Flores, Efren J.; Muse, Victorine V.; Shepard, Jo-Anne O.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Lennes, Inga T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Fintelmann, FJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 202, Boston, MA 02114 USA. EM fintelmann@mgh.harvard.edu NR 50 TC 6 Z9 6 U1 0 U2 1 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 NOV-DEC PY 2015 VL 35 IS 7 BP 1894 EP 1909 DI 10.1148/rg.2015150079 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DB2MX UT WOS:000368344100004 PM 26495797 ER PT J AU Anvari, A Forsberg, F Samir, AE AF Anvari, Arash Forsberg, Flemming Samir, Anthony E. TI A Primer on the Physical Principles of Tissue Harmonic Imaging SO RADIOGRAPHICS LA English DT Article ID FOCAL HEPATIC-LESIONS; B-MODE SONOGRAPHY; MEDICAL ULTRASOUND; GRAY-SCALE; CONVENTIONAL SONOGRAPHY; NONLINEAR PROPAGATION; BREAST SONOGRAPHY; INVERSION; US; ULTRASONOGRAPHY AB Tissue harmonic imaging (THI) is a routinely used component of diagnostic ultrasonography (US). In this method, higher-frequency harmonic waves produced by nonlinear fundamental US wave propagation are used to generate images that contain fewer artifacts than those seen on conventional fundamental wave US tissue imaging. Harmonic frequencies are integer multiples of the fundamental frequency. The majority of current clinical US systems use second harmonic echoes for THI image formation. Image processing techniques (ie, bandwidth receive filtering, pulse inversion, side-by-side phase cancellation, and pulse-coded harmonics) are used to eliminate the fundamental frequency echoes, and the remaining harmonic frequency data are used to generate the diagnostic image. Advantages of THI include improved signal-to-noise ratio and reduced artifacts produced by side lobes, grating lobes, and reverberation. THI has been accepted in US practice, and variations of the technology are available on most US systems typically used for diagnostic imaging in radiologic practice. Differential THI is a further improvement that combines the advantages of THI, including superior tissue definition and reduced speckle artifact, with the greater penetration of lower frequency US, which permits high-quality harmonic imaging at greater depth than could previously be performed with conventional THI. (C) RSNA, 2015 C1 [Anvari, Arash; Samir, Anthony E.] Harvard Univ, Sch Med, Dept Radiol, Ultra Sound Div,Massachusetts Gen Hosp, Boston, MA 02114 USA. [Forsberg, Flemming] Thomas Jefferson Univ, Dept Radiol, Ultrasound Div, Philadelphia, PA 19107 USA. RP Samir, AE (reprint author), Harvard Univ, Sch Med, Dept Radiol, Ultra Sound Div,Massachusetts Gen Hosp, 55 Fruit St,White 270, Boston, MA 02114 USA. EM asamir@mgh.harvard.edu RI Anvari, Arash/B-4329-2014 OI Anvari, Arash/0000-0001-5887-581X FU National Institutes of Health; Department of Defense; Toshiba; General Electric FX F.F. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: grants from the National Institutes of Health, the Department of Defense, and Toshiba; personal fees from General Electric and Toshiba; and nonfinancial support from General Electric, Toshiba, and Siemens. Other activities: disclosed no relevant relationships. NR 50 TC 1 Z9 1 U1 0 U2 4 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 NOV-DEC PY 2015 VL 35 IS 7 BP 1956 EP 1965 DI 10.1148/rg.2015140338 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DB2MX UT WOS:000368344100009 PM 26562232 ER PT J AU Abramson, ZR Peacock, ZS Cohen, HL Choudhri, AF AF Abramson, Zachary R. Peacock, Zachary S. Cohen, Harris L. Choudhri, Asim F. TI Radiology of Cleft Lip and Palate: Imaging for the Prenatal Period and throughout Life SO RADIOGRAPHICS LA English DT Article ID OBSTRUCTIVE SLEEP-APNEA; MAXILLARY ADVANCEMENT; STICKLER-SYNDROME; ROBIN-SEQUENCE; DIAGNOSIS; SURGERY; MRI; EPIDEMIOLOGY; ULTRASOUND; CHILDREN AB Recent advances in prenatal imaging have made possible the in utero diagnosis of cleft lip and palate and associated deformities. Postnatal diagnosis of cleft lip is made clinically, but imaging still plays a role in detection of associated abnormalities, surgical treatment planning, and screening for or surveillance of secondary deformities. This article describes the clinical entities of cleft lip with or without cleft palate (CLP) and isolated cleft palate and documents their prenatal and postnatal appearances at radiography, ultrasonography (US), magnetic resonance (MR) imaging, and computed tomography (CT). Imaging protocols and findings for prenatal screening, detection of associated anomalies, and evaluation of secondary deformities throughout life are described and illustrated. CLP and isolated cleft palate are distinct entities with shared radiologic appearances. Prenatal US and MR imaging can depict clefting of the lip or palate and associated anomalies. While two- and three-dimensional US often can depict cleft lip, visualization of cleft palate is more difficult, and repeat US or fetal MR imaging should be performed if cleft palate is suspected. Postnatal imaging can assist in identifying associated abnormalities and dentofacial deformities. Dentofacial sequelae of cleft lip and palate include missing and supernumerary teeth, oronasal fistulas, velopharyngeal insufficiency, hearing loss, maxillary growth restriction, and airway abnormalities. Secondary deformities can often be found incidentally at imaging performed for other purposes, but detection is necessary because they may have considerable implications for the patient. (C) RSNA, 2015. C1 [Abramson, Zachary R.] Univ Tennessee, Ctr Hlth Sci, Coll Med, Memphis, TN 38163 USA. [Peacock, Zachary S.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Cohen, Harris L.; Choudhri, Asim F.] Le Bonheur Childrens Hosp, Dept Radiol, Memphis, TN 38103 USA. RP Choudhri, AF (reprint author), Le Bonheur Childrens Hosp, Dept Radiol, 848 Adams Ave,Room G216, Memphis, TN 38103 USA. EM achoudhri@uthsc.edu NR 56 TC 0 Z9 0 U1 2 U2 5 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 NOV-DEC PY 2015 VL 35 IS 7 BP 2054 EP 2064 DI 10.1148/rg.2015150050 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DB2MX UT WOS:000368344100015 PM 26562237 ER PT J AU Matalon, SA Mamon, HJ Fuchs, CS Doyle, LA Tirumani, H Ramaiya, NH Rosenthal, MH AF Matalon, Shanna A. Mamon, Harvey J. Fuchs, Charles S. Doyle, Leona A. Tirumani, Sree Harsha Ramaiya, Nikhil H. Rosenthal, Michael H. TI Anorectal Cancer: Critical Anatomic and Staging Distinctions That Affect Use of Radiation Therapy SO RADIOGRAPHICS LA English DT Article ID CIRCUMFERENTIAL RESECTION MARGIN; PRIMARY RECTAL-CANCER; ANAL CANCER; COLORECTAL-CANCER; HISTOPATHOLOGIC FINDINGS; RISK-FACTORS; FDG-PET/CT; CARCINOMA; MANAGEMENT; METAANALYSIS AB Although rectal and anal cancers are anatomically close, they are distinct entities with different histologic features, risk factors, staging systems, and treatment pathways. Imaging is at the core of initial clinical staging of these cancers and most commonly includes magnetic resonance imaging for local-regional staging and computed tomography for evaluation of metastatic disease. The details of the primary tumor and involvement of regional lymph nodes are crucial in determining if and how radiation therapy should be used in treatment of these cancers. Unfortunately, available imaging modalities have been shown to have imperfect accuracy for identification of nodal metastases and imaging features other than size. Staging of nonmetastatic rectal cancers is dependent on the depth of invasion (T stage) and the number of involved regional lymph nodes (N stage). Staging of nonmetastatic anal cancers is determined according to the size of the primary mass and the combination of regional nodal sites involved; the number of positive nodes at each site is not a consideration for staging. Patients with T3 rectal tumors and/or involvement of perirectal, mesenteric, and internal iliac lymph nodes receive radiation therapy. Almost all anal cancers warrant use of radiation therapy, but the extent and dose of the radiation fields is altered on the basis of both the size of the primary lesion and the presence and extent of nodal involvement. The radiologist must recognize and report these critical anatomic and staging distinctions, which affect use of radiation therapy in patients with anal and rectal cancers. (C) RSNA, 2015 C1 [Matalon, Shanna A.; Tirumani, Sree Harsha; Ramaiya, Nikhil H.; Rosenthal, Michael H.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Mamon, Harvey J.] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. [Doyle, Leona A.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Mamon, Harvey J.; Fuchs, Charles S.; Doyle, Leona A.; Tirumani, Sree Harsha; Ramaiya, Nikhil H.; Rosenthal, Michael H.] Harvard Univ, Sch Med, Boston, MA USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Tirumani, Sree Harsha; Ramaiya, Nikhil H.; Rosenthal, Michael H.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. RP Matalon, SA (reprint author), Mellins Lib, 75 Francis St, Boston, MA 02115 USA. EM smatalon@partners.org FU National Institutes of Health [5P50CA127003, R01CA149222, R01CA118553]; National Cancer Institute [5P30CA06516] FX C.S.F. supported by the National Institutes of Health [grant numbers 5P50CA127003, R01CA149222, R01CA118553] and the National Cancer Institute [grant number 5P30CA06516]. NR 65 TC 1 Z9 1 U1 2 U2 2 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 NOV-DEC PY 2015 VL 35 IS 7 BP 2091 EP 2108 DI 10.1148/rg.2015150037 PG 18 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DB2MX UT WOS:000368344100018 PM 26562239 ER PT J AU Samir, AE Dhyani, M Anvari, A Prescott, J Halpern, EF Faquin, WC Stephen, A AF Samir, Anthony E. Dhyani, Manish Anvari, Arash Prescott, Jason Halpern, Elkan F. Faquin, William C. Stephen, Antonia TI Shear-Wave Elastography for the Preoperative Risk Stratification of Follicular-patterned Lesions of the Thyroid: Diagnostic Accuracy and Optimal Measurement Plane SO RADIOLOGY LA English DT Article ID FINE-NEEDLE-ASPIRATION; GENE-EXPRESSION CLASSIFIER; TIME ULTRASOUND ELASTOGRAPHY; DIFFERENTIAL-DIAGNOSIS; PROSPECTIVE MULTICENTER; INDETERMINATE CYTOLOGY; SERUM THYROGLOBULIN; BETHESDA SYSTEM; FROZEN-SECTION; NODULES AB Purpose: To evaluate the diagnostic accuracy of shear-wave elastography (SWE) for the diagnosis of malignancy in follicular lesions and to identify the optimal SWE measurement plane. Materials and Methods: The institutional review board approved this HIPAA-compliant, single-institution, prospective pilot study. Subjects scheduled for surgery after a previous fine-needle aspiration report of "atypia of undetermined significance" or "follicular lesion of undetermined significance," "suspicion for follicular neoplasm," or "suspicion for Hurthle cell neoplasm," were enrolled after obtaining informed consent. Subjects underwent conventional ultrasonography (US), Doppler evaluation, and SWE preoperatively, and their predictive value for thyroid malignancy was evaluated relative to the reference standard of surgical pathologic findings. Results: Thirty-five patients (12 men, 23 women) with a mean age of 55 years (range, 23-85 years) and a fine-needle aspiration diagnosis of atypia of undetermined significance or follicular lesion of undetermined significance (n = 16), suspicion for follicular neoplasm (n = 14), and suspicion for Hurthle cell neoplasm (n = 5) were enrolled in the study. Male sex was a statistically significant (P = .02) predictor of malignancy, but age was not. No sonographic morphologic parameter, including nodule size, microcalcification, macrocalcification, halo sign, taller than wide dimension, or hypoechogenicity, was associated with malignancy. Similarly, no Doppler feature, including intranodular vascularity, pulsatility index, resistive index, or peak-systolic velocity, was associated with malignancy. Higher median SWE tissue Young modulus estimates from the transverse insonation plane were associated with malignancy, yielding an area under the receiver operating characteristic curve of 0.81 (95% confidence interval: 0.62, 1.00) for differentiation of malignant from benign nodules. At a cutoff value of 22.3 kPa, sensitivity, specificity, positive predictive value, and negative predictive value of 82%, 88%, 75%, and 91%, respectively, were observed. Conclusion: This prospective pilot study indicates that SWE may be a valuable tool in preoperative malignancy risk assessment of follicular-patterned thyroid nodules. (C) RSNA, 2015 C1 [Samir, Anthony E.; Dhyani, Manish; Anvari, Arash] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Halpern, Elkan F.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Faquin, William C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Stephen, Antonia] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Prescott, Jason] Johns Hopkins Sch Med, Dept Surg, Baltimore, MD USA. RP Samir, AE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM asamir@mgh.harvard.edu RI Anvari, Arash/B-4329-2014; OI Anvari, Arash/0000-0001-5887-581X; Dhyani, Manish/0000-0002-2651-1859 NR 64 TC 12 Z9 12 U1 2 U2 4 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 NOV PY 2015 VL 277 IS 2 BP 565 EP 573 DI 10.1148/radiol.2015141627 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DB3TQ UT WOS:000368435100033 PM 25955578 ER PT J AU Barkai, U Avni, Y Ludwig, B Colton, CC Weir, GC Zimermann, B Maimon, S Steffen, A Goldman, T de Vos, P Borenstein, SR Rotem, A AF Barkai, Uriel Avni, Yuval Ludwig, Barbara Colton, Clark C. Weir, Gordon C. Zimermann, Baruch Maimon, Shiri Steffen, Anja Goldman, Tali de Vos, Paul Borenstein, Stefan R. Rotem, Avi TI COMPOSITE MEMBRANE PROTECTING IMPLANTED ISLETS FROM ALLOGENIC AND XENOGENEIC HOST IMMUNE SYSTEM. SO TRANSPLANTATION LA English DT Meeting Abstract CT Joint Congress of the International-Pancreas-and-Islet-Transplantation-Association, International-Xenotransplantation-Association and Cell-Transplant-Society CY NOV 15-19, 2015 CL Melbourne, AUSTRALIA SP Int Pancreas & Islet Transplantat Assoc, Int Xenotransplantat Assoc, Cell Transplant Soc C1 [Barkai, Uriel; Avni, Yuval; Zimermann, Baruch; Maimon, Shiri; Goldman, Tali; Rotem, Avi] Beta O2 Technol, Rosh Haayin, Israel. [Ludwig, Barbara; Steffen, Anja; Borenstein, Stefan R.] Paul Langerhans Inst, Clin Carl Gus Carus TU, Dresden, Germany. [Colton, Clark C.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [de Vos, Paul] Univ Med Ctr Groningen, Dept Pathol, NL-9713 AV Groningen, Netherlands. [Weir, Gordon C.] Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD NOV PY 2015 VL 99 IS 11 SU 2 MA 580 BP S150 EP S150 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DB6LE UT WOS:000368625700213 ER PT J AU Carrico, R Fridell, J Odorico, J Yeh, H Tyler, K Niederhaus, S AF Carrico, Robert Fridell, Jonathan Odorico, Jon Yeh, Heidi Tyler, Kristina Niederhaus, Silke TI WHY ARE PANCREAS TRANSPLANT VOLUMES IN THE UNITED STATES DECLINING? SO TRANSPLANTATION LA English DT Meeting Abstract CT Joint Congress of the International-Pancreas-and-Islet-Transplantation-Association, International-Xenotransplantation-Association and Cell-Transplant-Society CY NOV 15-19, 2015 CL Melbourne, AUSTRALIA SP Int Pancreas & Islet Transplantat Assoc, Int Xenotransplantat Assoc, Cell Transplant Soc C1 [Carrico, Robert; Tyler, Kristina] United Network Organ Sharing, Res, Richmond, VA USA. [Fridell, Jonathan] Indiana Univ, Surg, Indianapolis, IN 46204 USA. [Odorico, Jon] Univ Wisconsin, Surg, Madison, WI USA. [Yeh, Heidi] Massachusetts Gen Hosp, Surg, Boston, MA 02114 USA. [Niederhaus, Silke] Univ Maryland, Surg, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD NOV PY 2015 VL 99 IS 11 SU 2 MA 265 BP S26 EP S26 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DB6LE UT WOS:000368625700037 ER PT J AU Colton, C Evron, Y Ludwig, B Weir, GC Zimmerman, B Maimon, S Neufield, T Shalev, N Goldman, T Leon, A Yavriyants, K Shabtay, N Rozenshtein, T DiIenno, AR Stefan, A Vardi, P Bloch, K de Vos, P Bornstein, SR Barkai, U Rotem, A AF Colton, Clark Evron, Y. Ludwig, B. Weir, G. C. Zimmerman, B. Maimon, S. Neufield, T. Shalev, N. Goldman, T. Leon, A. Yavriyants, K. Shabtay, N. Rozenshtein, T. DiIenno, A. R. Stefan, A. Vardi, P. Bloch, K. de Vos, P. Bornstein, S. R. Barkai, U. Rotem, A. TI ENHANCED OXYGEN SUPPLY TO ISLETS ENCAPSULATED AT HIGH DENSITY LEADS TO LONG-TERM NORMOGLYCENIA IN DIABETIC RATS AND FACILITATES DEVELOPMENT OF SMALLER DEVICES. SO TRANSPLANTATION LA English DT Meeting Abstract CT Joint Congress of the International-Pancreas-and-Islet-Transplantation-Association, International-Xenotransplantation-Association and Cell-Transplant-Society CY NOV 15-19, 2015 CL Melbourne, AUSTRALIA SP Int Pancreas & Islet Transplantat Assoc, Int Xenotransplantat Assoc, Cell Transplant Soc C1 [Colton, Clark; DiIenno, A. R.; Barkai, U.; Rotem, A.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Evron, Y.; Zimmerman, B.; Maimon, S.; Neufield, T.; Shalev, N.; Goldman, T.; Leon, A.; Yavriyants, K.; Shabtay, N.; Rozenshtein, T.] Beta O2 Technol, Rosh Haain, Israel. [Ludwig, B.; Stefan, A.; Bornstein, S. R.] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Med 3, D-01062 Dresden, Germany. [Weir, G. C.] Joslin Diabet Ctr, Div Res, Sect Islet Trasnplantat & Cell Biol 4, Boston, MA 02215 USA. [Vardi, P.; Bloch, K.] Tel Aviv Univ, Sackler Sch Med, Feisenstein Med Res Ctr, Petah Tiqwa, Israel. [de Vos, P.] Univ Med Ctr Groningen, Dept Pathol & Lab Med, NL-9713 AV Groningen, Netherlands. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD NOV PY 2015 VL 99 IS 11 SU 2 MA 535 BP S127 EP S127 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DB6LE UT WOS:000368625700182 ER PT J AU Salama, A Conchon, S Perota, A Martinet, B Judor, JP Evanno, G Bernardet, SL Le Berre, L Hervouet, J Minault, D Concordet, JP Dugast, E Vanhove, B Abadie, J Gaide, N Lagutina, I Duchi, R Lazzari, G Floch, R Duvaux, O Toutain, PL Maillasson, M Sachs, DH Gauthier, O Brouard, S Cozzi, E Blancho, G Perreault, H Bach, JM Galli, C Soulillou, JP AF Salama, Apolline Conchon, Sophie Perota, Andrea Martinet, Bernard Judor, Jean-Paul Evanno, Gwenaelle Bernardet, Stephanie Le-Bas Le Berre, Ludmilla Hervouet, Jeremy Minault, David Concordet, Jean-Paul Dugast, Emilie Vanhove, Bernard Abadie, Jerome Gaide, Nicolas Lagutina, Irina Duchi, Roberto Lazzari, Giovanna Floch, Robert Duvaux, Odile Toutain, Pierre-Louis Maillasson, Mike Sachs, David H. Gauthier, Olivier Brouard, Sophie Cozzi, Emanuele Blancho, Gilles Perreault, Helene Bach, Jean-Marie Galli, Cesare Soulillou, Jean-Paul TI IMMUNE PHENOTYPE AND IGG CHARACTERISTICS OF NEU5GC AND ALPHA-1-3-GAL DOUBLE KNOCK-OUT PIGS. SO TRANSPLANTATION LA English DT Meeting Abstract CT Joint Congress of the International-Pancreas-and-Islet-Transplantation-Association, International-Xenotransplantation-Association and Cell-Transplant-Society CY NOV 15-19, 2015 CL Melbourne, AUSTRALIA SP Int Pancreas & Islet Transplantat Assoc, Int Xenotransplantat Assoc, Cell Transplant Soc C1 [Salama, Apolline; Conchon, Sophie; Martinet, Bernard; Judor, Jean-Paul; Evanno, Gwenaelle; Bernardet, Stephanie Le-Bas; Le Berre, Ludmilla; Hervouet, Jeremy; Minault, David; Dugast, Emilie; Vanhove, Bernard; Brouard, Sophie; Blancho, Gilles; Soulillou, Jean-Paul] Univ Nantes, CHU Nantes, INSERM, Inst Transplantat Urol Nephrol,UMR 1064, Nantes, France. [Salama, Apolline] Soc Accelerat Transfert Technol Ouest Valorisat, Rennes, France. [Perota, Andrea; Lagutina, Irina; Duchi, Roberto; Lazzari, Giovanna; Galli, Cesare] Avantea, Lab Reprod Technol, Cremona, Italy. [Evanno, Gwenaelle; Floch, Robert; Duvaux, Odile] Xenothera, Nantes, France. [Concordet, Jean-Paul] MNHN USM503, CNRS, INSERM, U565,UMR7196, Paris, France. [Abadie, Jerome; Gaide, Nicolas] ONIRIS Nantes Atlantic Coll Vet Med & Food Sci, AMaROC, Nantes, France. [Toutain, Pierre-Louis] UMR 1331 INRA ENVT, Toulouse, France. [Toutain, Pierre-Louis] Ecole Natl Vet Toulouse, Toulouse, France. [Maillasson, Mike] Univ Nantes, CRCNA UMR INSERM 892, Plateforme IMPACT Biogenouest, Nantes, France. [Sachs, David H.] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Ctr Transplantat Sci, Boston, MA 02114 USA. [Gauthier, Olivier] ONIRIS, Ctr Rech & Invest Preclin, Nantes, Italy. [Cozzi, Emanuele] Padua Hosp, Padua, Italy. [Cozzi, Emanuele] Consortium Res Organ Transplantat, Padua, Italy. [Perreault, Helene] Univ Manitoba, Dept Chem, Winnipeg, MB R3T 2N2, Canada. [Bach, Jean-Marie] Univ Nantes, ONIRIS INRA USC1383, ONIRIS, IECM,EA4644, Nantes, France. [Galli, Cesare] Univ Bologna, Dept Vet Med Sci, Bologna, Italy. RI Toutain, Pierre-Louis/G-4540-2011; concordet, jean-paul/C-3417-2015 OI Toutain, Pierre-Louis/0000-0002-8846-8892; NR 0 TC 0 Z9 0 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD NOV PY 2015 VL 99 IS 11 SU 2 MA 348 BP S61 EP S61 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DB6LE UT WOS:000368625700083 ER PT J AU Schuetz, C Yi, P Markmann, JF AF Schuetz, Christian Yi, Peng Markmann, James F. TI THE INSULIN RECEPTOR ANTAGONIST S961 INDUCES MINIMAL PROLIFERATION OF PANCREATIC BETA CELLS IN NON-HUMAN PRIMATES SO TRANSPLANTATION LA English DT Meeting Abstract CT Joint Congress of the International-Pancreas-and-Islet-Transplantation-Association, International-Xenotransplantation-Association and Cell-Transplant-Society CY NOV 15-19, 2015 CL Melbourne, AUSTRALIA SP Int Pancreas & Islet Transplantat Assoc, Int Xenotransplantat Assoc, Cell Transplant Soc C1 [Schuetz, Christian; Markmann, James F.] Massachusetts Gen Hosp, Transplant Surg, Boston, MA 02114 USA. [Yi, Peng] Joslin Diabet Ctr, Islet Cell & Regenerat Biol Sec, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD NOV PY 2015 VL 99 IS 11 SU 2 MA 919 BP S297 EP S297 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DB6LE UT WOS:000368625700435 ER PT J AU Tena, A Sachs, DH Mallard, C Yang, YG Tasaki, M Farkash, E Colvin, RB Leonard, DA Hawley, R AF Tena, Aseda Sachs, David H. Mallard, Christopher Yang, Yong-Guang Tasaki, Masayuki Farkash, Evan Colvin, Robert B. Leonard, David A. Hawley, Robert TI PROLONGED SURVIVAL OF PORCINE SKIN ON BABOONS FOLLOWING ADMINISTRATION OF PORCINE CELLS EXPRESSING HUMAN CD47. SO TRANSPLANTATION LA English DT Meeting Abstract CT Joint Congress of the International-Pancreas-and-Islet-Transplantation-Association, International-Xenotransplantation-Association and Cell-Transplant-Society CY NOV 15-19, 2015 CL Melbourne, AUSTRALIA SP Int Pancreas & Islet Transplantat Assoc, Int Xenotransplantat Assoc, Cell Transplant Soc C1 [Tena, Aseda; Sachs, David H.; Mallard, Christopher; Tasaki, Masayuki; Leonard, David A.; Hawley, Robert] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. [Yang, Yong-Guang; Farkash, Evan; Colvin, Robert B.] Columbia Univ, Columbia Ctr Translat Immunol, New York, NY USA. Massachusetts Gen Hosp, Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD NOV PY 2015 VL 99 IS 11 SU 2 MA 376 BP S73 EP S73 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DB6LE UT WOS:000368625700104 ER PT J AU Wang, LJ Kin, T O'Gorman, D Shapiro, AMJ Naziruddin, B Takita, M Levy, MF Posselt, A Szot, G Savari, O Barbaro, B McGarrigle, J Yeh, CC Oberholzer, J Lei, J Chen, T Markmann, JF Kim, JI Alvarez, A Linetsky, E Ricordi, C Balamurugan, AN Loganathan, G Wilhelm, JJ Hering, BJ Bottino, R Trucco, M Liu, CY Min, Z Li, YJ Naji, A Fernandez, LA Ziemelis, M Danobeitia, JS Millis, JM Wikowski, P AF Wang, Ling-jia Kin, Tatsuya O'Gorman, Doug Shapiro, A. M. James Naziruddin, Bashoo Takita, Morihito Levy, Marlon F. Posselt, Andrew Szot, Gregory Savari, Omid Barbaro, Barbara McGarrigle, James Yeh, Chun Chieh Oberholzer, Jose Lei, Ji Chen, Tao Markmann, James F. Kim, James I. Alvarez, Alejandro Linetsky, Elina Ricordi, Camillo Balamurugan, A. N. Loganathan, Gopalakrishnan Wilhelm, Joshua J. Hering, Bernard. J. Bottino, Rita Trucco, Massimo Liu, Chengyang Min, Zaw Li, Yanjing Naji, Ali Fernandez, Luis A. Ziemelis, Marty Danobeitia, Juan S. Millis, J. Michael Wikowski, Piotr TI NORTH AMERICA ISLET DONOR SCORE IN DONOR PANCREAS SELECTION FOR SUCCESSFUL ISLET ISOLATION FOR TRANSPLANTATION - A MULTICENTER STUDY. SO TRANSPLANTATION LA English DT Meeting Abstract CT Joint Congress of the International-Pancreas-and-Islet-Transplantation-Association, International-Xenotransplantation-Association and Cell-Transplant-Society CY NOV 15-19, 2015 CL Melbourne, AUSTRALIA SP Int Pancreas & Islet Transplantat Assoc, Int Xenotransplantat Assoc, Cell Transplant Soc C1 [Kin, Tatsuya; O'Gorman, Doug; Shapiro, A. M. James] Univ Alberta, Clin Islet Transplant Program, Edmonton, AB, Canada. [Kin, Tatsuya; O'Gorman, Doug; Shapiro, A. M. James] Alberta Hlth Serv, Edmonton, AB, Canada. [Naziruddin, Bashoo; Takita, Morihito; Levy, Marlon F.] Baylor Simmons Transplant Inst, Dallas, TX USA. [Posselt, Andrew; Szot, Gregory] Univ Calif San Francisco, UCSF Transplantat Surg, San Francisco, CA 94143 USA. [Wang, Ling-jia; Savari, Omid; Millis, J. Michael; Wikowski, Piotr] Univ Chicago, Dept Surg, Sect Transplantat, 5841 S Maryland Ave, Chicago, IL 60637 USA. [Wang, Ling-jia; Barbaro, Barbara; McGarrigle, James; Yeh, Chun Chieh; Oberholzer, Jose] Univ Illinois, UIC Cell Isolat Program, Chicago, IL USA. [Lei, Ji; Chen, Tao; Markmann, James F.; Kim, James I.] Massachusetts Gen Hosp, Ctr Transplantat Sci, Boston, MA 02114 USA. [Alvarez, Alejandro; Linetsky, Elina; Ricordi, Camillo] Univ Miami, Miller Sch Med, Diabet Res Inst, cGMP Cell Proc Facil, Miami, FL 33136 USA. [Balamurugan, A. N.; Loganathan, Gopalakrishnan; Wilhelm, Joshua J.; Hering, Bernard. J.] Univ Minnesota, Schulze Diabet Inst, Minneapolis, MN USA. [Bottino, Rita; Trucco, Massimo] Allegheny Hlth Network, Inst Cellular Therapeut, Pittsburgh, PA USA. [Liu, Chengyang; Min, Zaw; Li, Yanjing; Naji, Ali] Univ Penn, Div Transplantat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Fernandez, Luis A.; Ziemelis, Marty; Danobeitia, Juan S.] Univ Wisconsin, Div Organ Transplantat, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD NOV PY 2015 VL 99 IS 11 SU 2 MA 1043 BP S317 EP S317 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DB6LE UT WOS:000368625700466 ER PT J AU Weitlauf, JC LaCroix, AZ Bird, CE Woods, NF Washington, DL Katon, JG LaMonte, MJ Goldstein, MK Bassuk, SS Sarto, GE Stefanick, ML AF Weitlauf, Julie C. LaCroix, Andrea Z. Bird, Chloe E. Woods, Nancy F. Washington, Donna L. Katon, Jodie G. LaMonte, Michael J. Goldstein, Mary K. Bassuk, Shari S. Sarto, Gloria E. Stefanick, Marcia L. TI Prospective Analysis of Health and Mortality Risk in Veteran and Non-Veteran Participants in the Women's Health Initiative SO WOMENS HEALTH ISSUES LA English DT Article ID VIETNAM-ERA VETERANS; MILITARY SERVICE; HIP FRACTURE; US MILITARY; CANCER; PATTERNS; VALIDITY; DEATH; RATES; PLUS AB Background: The health of postmenopausal women veterans is a neglected area of study. A stronger empirical evidence base is needed, and would inform the provision of health care for the nearly 1 million U.S. women veterans currently 50 years of age or older. To this end, the present work compares salient health outcomes and risk of all-cause mortality among veteran and non-veteran participants of the Women's Health Initiative (WHI). Methods: This study features prospective analysis of long-term health outcomes and mortality risk (average follow-up, 8 years) among the 3,706 women veterans and 141,009 non-veterans who participated in the WHI Observational Study or Clinical Trials. Outcome measurements included confirmed incident cases of cardiovascular disease (CVD), cancer, diabetes, hip fractures, and all-cause mortality. Results: We identified 17,968 cases of CVD, 19,152 cases of cancer, 18,718 cases of diabetes, 2,817 cases of hip fracture, and 13,747 deaths. In Cox regression models adjusted for age, sociodemographic variables, and health risk factors, veteran status was associated with significantly increased risk of all-cause mortality (hazard ratio [HR], 1.13; 95% CI, 1.03-1.23), but not with risk of CVD (HR, 1.00; 95% CI, 0.90-1.11), cancer (HR, 1.04; 95% CI, 0.95-1.14), hip fracture (HR, 1.16; 95% CI, 0.94-1.43), or diabetes (HR, 1.00; 95% CI, 0.89-1.1). Conclusions: Women veterans' postmenopausal health, particularly risk for all-cause mortality, warrants further consideration. In particular, efforts to identify and address modifiable risk factors associated with all-cause mortality are needed. Published by Elsevier Inc. on behalf of the Jacobs Institute of Women's Health. C1 [Weitlauf, Julie C.] VA Palo Alto Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Palo Alto, CA USA. [Weitlauf, Julie C.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [LaCroix, Andrea Z.] Univ Calif San Diego, Div Epidemiol Family & Prevent Med, La Jolla, CA 92093 USA. [Bird, Chloe E.] RAND Corp, Santa Monica, CA USA. [Bird, Chloe E.] Pardee RAND Grad Sch, Santa Monica, CA USA. [Woods, Nancy F.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [Washington, Donna L.] VA Greater Los Angeles Hlth Care Syst, Ctr Study Healthcare Innovat Implementat & Policy, Los Angeles, CA USA. [Washington, Donna L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Katon, Jodie G.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Katon, Jodie G.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [LaMonte, Michael J.] SUNY Buffalo, Dept Epidemiol & Environm Hlth, Sch Publ Hlth & Hlth Profess, Buffalo, NY 14260 USA. [Goldstein, Mary K.] VA Palo Alto Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Palo Alto, CA USA. [Goldstein, Mary K.] Stanford Univ, Dept Med, Ctr Primary Care & Outcomes Res, Sch Med, Stanford, CA 94305 USA. [Bassuk, Shari S.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Sarto, Gloria E.] Univ Wisconsin, Dept Obstet & Gynecol, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Stefanick, Marcia L.] Stanford Univ, Dept Med, Sch Med, Stanford Ctr Prevent Res, Stanford, CA 94305 USA. RP Weitlauf, JC (reprint author), VA Palo Alto Hlth Care Syst 151 Y, 3801 Miranda Ave, Palo Alto, CA 94304 USA. EM wjulie1@stanford.edu FU National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100 004C, HHSN271201100004C]; Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development Division, Career Development Award [CD206035] FX The Women's Health Initiative (WHI) program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100 004C, and HHSN271201100004C.; Dr. Weitlauf's contribution to this work was supported in part by the Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development Division, Career Development Award [CD206035 2 to J.W.]. To the extent that the funding agencies associated with this project played no role (beyond financial support) in the development or execution of the study described, all investigators (authors) are independent from the sources of study funding. NR 46 TC 11 Z9 11 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD NOV-DEC PY 2015 VL 25 IS 6 BP 649 EP 657 DI 10.1016/j.whi.2015.08.006 PG 9 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA DB1DH UT WOS:000368247700010 PM 26432346 ER PT J AU Wagner, C Dichter, ME Mattocks, K AF Wagner, Clara Dichter, Melissa E. Mattocks, Kristin TI Women Veterans' Pathways to and Perspectives on Veterans Affairs Health Care SO WOMENS HEALTH ISSUES LA English DT Article ID CENTERED MEDICAL HOME; PATIENT SATISFACTION; QUALITY; PERCEPTIONS; PREDICTORS; GENDER AB Background: We examined Veterans Affairs (VA) health care experiences among contemporary women veteran patients receiving care at a VA medical center. Specifically, we examined women veteran patients' satisfaction with VA care along dimensions in line with patient-centered medical home (patient-aligned care teams [PACT] in VA) priorities, and pathways through which women initially accessed VA care. Methods: We used a mixed methods research design. First, 249 racially diverse women (ages 22-64) who were past-year users of primary care at a VA medical center completed interviewer-administered surveys in 2012 assessing ratings of satisfaction with care in the past year. We then conducted in-depth qualitative interviews of a subset of women surveyed (n = 25) to gain a deeper understanding of perspectives and experiences that shaped satisfaction with care and to explore women's initial pathways to VA care. Results: Ratings of satisfaction with VA care were generally high, with some variation by demographic characteristics. Qualitative interviews revealed perceptions of care centered on the following themes: 1) barriers to care delay needed medical care, while innovative care models facilitate access, 2) women value communication and coordination of care, and 3) personalized context of VA care, including gender sensitive care shapes women's perceptions. Pathways to VA care were characterized by initial delays, often attributable to lack of knowledge or negative perceptions of VA care. Informal social networks were instrumental in helping women to overcome barriers. Conclusions: Findings highlight convergence of women's preferences with PACT priorities of timely access to care, provider communication, and coordination of care, and suggest areas for improvement. Outreach is needed to address gaps in knowledge and negative perceptions. Initiatives to enhance women veterans' social networks may provide an information-sharing resource. Published by Elsevier Inc. on behalf of the Jacobs Institute of Women's Health. C1 [Wagner, Clara; Dichter, Melissa E.] Philadelphia VA Med Ctr, CHERP, Philadelphia, PA 19104 USA. [Mattocks, Kristin] VA Cent Western Massachusetts Healthcare Syst, Leeds, MA USA. [Mattocks, Kristin] Univ Massachusetts, Sch Med, Quantitat Hlth Sci & Psychiat, Worcester, MA USA. RP Wagner, C (reprint author), Philadelphia VA Med Ctr, CHERP, 4100 Chester Ave,Suite 202, Philadelphia, PA 19104 USA. EM Clara.Wagner@va.gov FU VA HSR&D Career Development Award [CDA 10-202]; VA VISN 4 Center for Evaluation of Patient Aligned Care Teams [CEPACT 12-005] FX This research was supported by a VA HSR&D Career Development Award (CDA 10-202) to Melissa Dichter and the VA VISN 4 Center for Evaluation of Patient Aligned Care Teams (CEPACT 12-005; PI: Dichter). The contents of this article do not necessarily represent the views of the U.S. Department of Veterans Affairs or the United States Government. NR 33 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 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD NOV-DEC PY 2015 VL 25 IS 6 BP 658 EP 665 DI 10.1016/j.whi.2015.06.009 PG 8 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA DB1DH UT WOS:000368247700011 PM 26341566 ER PT J AU Battaglia, TA Gunn, CM McCoy, ME Mu, HH Baranoski, AS Chiao, EY Kachnic, LA Stier, EA AF Battaglia, Tracy A. Gunn, Christine M. McCoy, Molly E. Mu, Helen H. Baranoski, Amy S. Chiao, Elizabeth Y. Kachnic, Lisa A. Stier, Elizabeth A. TI Beliefs About Anal Cancer among HIV-Infected Women: Barriers and Motivators to Participation in Research SO WOMENS HEALTH ISSUES LA English DT Article ID SQUAMOUS INTRAEPITHELIAL LESIONS; AFRICAN-AMERICAN PARTICIPATION; CHILDHOOD SEXUAL-ABUSE; HUMAN-PAPILLOMAVIRUS; CLINICAL-TRIALS; PTSD CHECKLIST; SELF-EFFICACY; HEALTH; VALIDATION; TRAUMA AB Background: Infection with the human immunodeficiency virus (HIV) remains associated with a greater risk of anal cancer, despite widespread use of combination antiretroviral therapy. Evidence concerning the acceptability of anal cancer screening gives little attention to women. Because HIV-infected women have a high prevalence of depression and history of sexual trauma, understanding acceptability among this group is critical. Purpose: We sought to assess barriers and motivators to participation in anal cancer screening research among a racial/ethnically diverse HIV-infected female population. Methods: We conducted a survey based on the Health Belief Model to identify characteristics of women willing to participate in anal cancer screening research (n = 200). Bivariate analyses examined associations between willingness to participate and sociodemographics, clinical characteristics, and health beliefs. Logistic regression modeled willingness to participate in research. Main Findings: Of the women who participated, 37% screened positive for depression, 43% reported a high trauma history, and 36% screened positive for posttraumatic stress disorder. Overall, 65% reported willingness to participate in research. Those likely to participate were older, reported intravenous drug use as their HIV risk factor, and had a history of prior high-resolution anoscopy (HRA) compared with those unwilling to participate. The most commonly reported barrier to anal Pap testing was fear of pain. In adjusted analyses, a lack of fear of pain and prior experience with HRA significantly predicted willingness to participate. Conclusions: Findings suggest that, to increase participation in anal Pap and HRA-related research for HIV-infected women, a single approach may not be adequate. Rather, we must harness patients' previous experiences and address psychosocial and financial concerns to overcome barriers to participation. Copyright (C) 2015 by the Jacobs Institute of Women's Health. Published by Elsevier Inc. C1 [Battaglia, Tracy A.; Gunn, Christine M.; McCoy, Molly E.] Boston Univ, Sch Med, Gen Internal Med Sect, Womens Hlth Unit, Boston, MA 02118 USA. [Battaglia, Tracy A.; Gunn, Christine M.; McCoy, Molly E.; Kachnic, Lisa A.] Boston Med Ctr, Boston, MA USA. [Mu, Helen H.; Stier, Elizabeth A.] Boston Univ, Med Ctr, Dept Obstet & Gynecol, Boston, MA USA. [Baranoski, Amy S.] Drexel Univ, Coll Med, Div Infect Dis & HIV Med, Philadelphia, PA 19104 USA. [Chiao, Elizabeth Y.] Baylor Coll Med, Dept Med, Michael E DeBakey Vet Affairs Med Ctr, Houston Hlth Serv Res & Dev Ctr Excellence, Houston, TX 77030 USA. [Kachnic, Lisa A.] Boston Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02118 USA. RP Gunn, CM (reprint author), Womens Hlth Unit, 801 Massachusetts Ave,First Floor, Boston, MA 02118 USA. EM Christine.Gunn@bmc.org OI Gunn, Christine/0000-0003-3340-2834 FU National Cancer Institute [U10 CA139519-02S]; National Cancer Institute Center [NCI U01 CA116892-0551]; Boston Medical Center Minority-Based Community Clinical Oncology Program [NCI 1U-10CA129519-01A1]; AIDS Malignancy Consortium [U01 CA121947]; Houston Health Services Research and Development Center for Excellence [FP90-020] FX This work was supported by the National Cancer Institute under Grant U10 CA139519-02S; National Cancer Institute Center to Reduce Cancer Health Disparities under Grant NCI U01 CA116892-0551; Boston Medical Center Minority-Based Community Clinical Oncology Program under Grant NCI 1U-10CA129519-01A1; the AIDS Malignancy Consortium under Grant U01 CA121947; and the Houston Health Services Research and Development Center for Excellence under Grant FP90-020. NR 49 TC 0 Z9 0 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 EI 1878-4321 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD NOV-DEC PY 2015 VL 25 IS 6 BP 720 EP 726 DI 10.1016/j.whi.2015.06.008 PG 7 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA DB1DH UT WOS:000368247700019 PM 26253825 ER PT J AU Singh, P Arora, S Lal, S Strand, TA Makharia, GK AF Singh, Prashant Arora, Shubhangi Lal, Suman Strand, Tor A. Makharia, Govind K. TI Risk of Celiac Disease in the First- and Second-Degree Relatives of Patients With Celiac Disease: A Systematic Review and Meta-Analysis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID GLUTEN-SENSITIVE ENTEROPATHY; 1ST-DEGREE RELATIVES; FOLLOW-UP; AT-RISK; FAMILIAL PREVALENCE; SEROLOGICAL MARKERS; CLINICAL PRESENTATION; DIAGNOSTIC-ACCURACY; UNITED-STATES; HLA-DQ AB OBJECTIVES: First-degree relatives (FDRs) of patients with celiac disease (CD) are at high risk for CD and prevalence among them varies from 1.6 to 38%. The risk of having CD among FDRs if the FDR is sister, brother, mother, father, son, or daughter of index patient with CD is not known. We conducted a meta-analysis and calculated pooled prevalence of CD among FDRs, second-degree relatives (SDRs), and specific relations with index patient. METHODS: On search of literature, 2,259 articles appeared of which 54 articles were included in this metaanalysis. Diagnosis of CD was based on standard criteria. RESULTS: Pooled prevalence of CD was 7.5% (95% confidence interval (CI) 6.3%, 8.8%) in 10,252 FDRs and 2.3% (95% CI 1.3%, 3.8%) in 642 SDRs. Pooled prevalence of CD was highest in siblings (8.9%), followed by offsprings (7.9%) and parents (3.0%). Female FDRs had higher prevalence than male FDRs (8.4% vs. 5.2%, P = 0.047). While sisters and daughters of index patient had the highest risk of having CD (1 in 7 and 1 in 8, respectively), the risk was 1 in 13 in sons, 1 in 16 in brothers, 1 in 32 in mothers, and 1 in 33 in fathers. There were also differences in the pooled prevalence of CD in FDRs according to their geographic location. CONCLUSIONS: Pooled prevalence of CD among FDRs is 7.5% and varies considerably with their relationship with the index patient. The risk of CD in FDRs also varies according to gender and geographical location. C1 [Singh, Prashant] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Arora, Shubhangi] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Lal, Suman] Max Healthcare, Gurgaon, India. [Strand, Tor A.] Innlandet Hosp Trust, Med Serv Div, Lillehammer, Norway. [Makharia, Govind K.] All India Inst Med Sci, Dept Gastroenterol & Human Nutr, New Delhi 110029, India. RP Makharia, GK (reprint author), All India Inst Med Sci, Dept Gastroenterol & Human Nutr, New Delhi 110029, India. EM govindmakharia@gmail.com RI Strand, Tor/D-9836-2016 OI Strand, Tor/0000-0002-4038-151X NR 87 TC 6 Z9 6 U1 6 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 EI 1572-0241 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD NOV PY 2015 VL 110 IS 11 BP 1539 EP 1548 DI 10.1038/ajg.2015.296 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DB1LO UT WOS:000368269900009 PM 26416192 ER PT J AU Hamilos, DL AF Hamilos, Daniel L. TI Pediatric chronic rhinosinusitis SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article ID ENDOSCOPIC SINUS SURGERY; REFRACTORY CHRONIC RHINOSINUSITIS; BACTERIAL BIOFILMS; NITRIC-OXIDE; ATOPIC-DERMATITIS; PARANASAL SINUSES; CHILDREN; MANAGEMENT; EXPRESSION; OUTCOMES AB The goal of this review is to elucidate the pathogenic factors, histopathologic features, and special considerations that relate to pediatric versus adult chronic rhinosinusitis (CRS) and to emphasize differences and similarities between the adult and pediatric conditions. Emphasis is placed on understanding of the differences in pathogenic mechanisms, host-microbial interactions, potential defects in innate antimicrobial immunity, and the role of biofilm formation in pediatric versus adult CRS and how these translate to different approaches toward both medical and surgical management. Pediatric CRS can be viewed as evolving from acute bacterial rhinosinusitis into an uncomplicated "early" stage of CRS, later evolving into a persistent stage and, in some cases, evolving into a late "maladaptive-eosinophilic" stage disease. Given this potential evolution toward more irreversible disease, a plea can be made for improved recognition of and more aggressive early intervention for pediatric CRS, it is hoped, to prevent these long-term consequences. For the primary care physician, this may necessitate enlisting the support of a sinus specialist before the symptoms of CRS have persisted for months or years. It may also necessitate, in some cases, the use of sinus computed tomography imaging to demonstrate that sinus abnormalities have resolved. Other arguments can be made for prompt and comprehensive management of pediatric CRS, including the need to reduce the burden of illness, reduce health care costs, avoid unnecessary antibiotic use and its attendant effects toward promoting antibiotic resistant infections and, potentially, to reduce the development of important comorbidities, e.g., asthma. C1 [Hamilos, Daniel L.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Hamilos, DL (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, 55 Fruit St,Bulfinch 422, Boston, MA 02114 USA. EM dhamilos@partners.org NR 80 TC 2 Z9 2 U1 0 U2 1 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 EI 1945-8932 J9 AM J RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD NOV-DEC PY 2015 VL 29 IS 6 BP 414 EP 420 DI 10.2500/ajra.2015.29.4238 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA DB2LQ UT WOS:000368340500018 PM 26637579 ER PT J AU Polnaszek, B Mirr, J Roiland, R Gilmore-Bykovskyi, A Hovanes, M Kind, A AF Polnaszek, Brock Mirr, Jacquelyn Roiland, Rachel Gilmore-Bykovskyi, Andrea Hovanes, Melissa Kind, Amy TI Omission of Physical Therapy Recommendations for High-Risk Patients Transitioning From the Hospital to Subacute Care Facilities SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Communication; Delivery of health care; Patient discharge; Patient discharge summaries; Patient readmission; Patient safety; Physical therapy specialty; Physicians; Rehabilitation; Subacute care ID SKILLED NURSING FACILITY; QUALITY-OF-LIFE; OLDER-ADULTS; DISCHARGE; STROKE; OUTCOMES; COMMUNICATION; CONTINUITY; PROGRAM; HAZARDS AB Objectives: To assess the quality and explore the potential impact of the communication of physical therapy (PT) recommendations in hospital discharge summaries/orders for high-risk subacute care populations, specifically targeting recommendations for (1) maintenance of patient safety, (2) assistance required for mobility, and (3) use of assistive devices. Design: Medical record abstraction of retrospective cohort comparing discharge recommendations made by inpatient PT to orders included in written hospital discharge summaries/orders, the primary form of hospital-to-subacute care communication. Data were linked to Medicare outcomes from corresponding years for all Medicare beneficiaries in the cohort. Setting: Academic hospital. Participants: All hospitalized patients (N = 613 overall) 18 years and older with primary diagnoses of stroke or hip fracture, with an inpatient PT consultation and discharged to subacute care during the years 2006 to 2008; 366 of these were Medicare beneficiaries. Interventions: Not applicable. Main Outcome Measures: Combined rehospitalization, emergency department visit, and/or death within 30 days of discharge. Results: Omission of recommendations for maintaining patient safety occurred in 54% (316/584) of patients; for assistance required for mobility, in approximately 100% (535/537); and for use of assistive devices, in 77% (409/532). As compared with those without patient safety restriction/precaution omissions, Medicare beneficiaries with such omissions demonstrated a trend toward more negative 30-day outcomes (26% vs 18%, P = .10). Similar, albeit nonsignificant, outcome trends were observed in the other omission categories. Conclusions: PT recommendations made during a hospital stay in high-risk patients are routinely omitted from hospital discharge communications to subacute care facilities. Interventions to reliably improve this communication are needed. (C) 2015 by the American Congress of Rehabilitation Medicine C1 [Polnaszek, Brock; Mirr, Jacquelyn; Hovanes, Melissa; Kind, Amy] Univ Wisconsin, Dept Med, Div Geriatr, Sch Med & Publ Hlth, Madison, WI USA. [Mirr, Jacquelyn; Roiland, Rachel; Gilmore-Bykovskyi, Andrea; Hovanes, Melissa; Kind, Amy] William S Middleton Hosp, Geriatr Res Educ & Clin Ctr, US Dept Vet Affairs, Madison, WI USA. [Roiland, Rachel; Gilmore-Bykovskyi, Andrea; Kind, Amy] Univ Wisconsin, Sch Nursing, Madison, WI USA. [Kind, Amy] Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA. RP Kind, A (reprint author), William S Middleton VA Hosp GRECC, 2500 Overlook Terrace, Madison, WI 53705 USA. EM ajk@medicine.wisc.edu RI Vila, Vanessa/B-4982-2014 FU National Institute on Aging and American Federation for Aging Research Medical Student Training in Aging Research Program; National Institute on Aging Beeson Career Development Award [K23AG034551]; National Institute on Aging, American Federation for Aging Research; John A. Hartford Foundation; Atlantic Philanthropies; Madison Veteran Affairs Geriatrics Research Education and Clinical Center [2014-25]; University of Wisconsin School of Medicine and Public Health's Community-Academic Partnerships core of University of Wisconsin Institute for Clinical and Translational Research [1UL1RR025011]; University of Wisconsin School of Medicine and Public Health from Wisconsin Partnership Program; National Hartford Centers of Gerontological Nursing Excellence FX Supported by the National Institute on Aging and American Federation for Aging Research Medical Student Training in Aging Research Program; a National Institute on Aging Beeson Career Development Award (award no. K23AG034551, funded by National Institute on Aging, American Federation for Aging Research, John A. Hartford Foundation, Atlantic Philanthropies, and Start Foundation); and in part by the Madison Veteran Affairs Geriatrics Research Education and Clinical Center (manuscript no. 2014-25); the University of Wisconsin School of Medicine and Public Health's Community-Academic Partnerships core of the University of Wisconsin Institute for Clinical and Translational Research (grant no. 1UL1RR025011); the University of Wisconsin School of Medicine and Public Health from the Wisconsin Partnership Program; and the National Hartford Centers of Gerontological Nursing Excellence. NR 36 TC 1 Z9 1 U1 3 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD NOV PY 2015 VL 96 IS 11 BP 1966 EP U239 DI 10.1016/j.apmr.2015.07.013 PG 10 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA DB1YX UT WOS:000368306600004 PM 26253350 ER PT J AU Hughes, AJ Hartoonian, N Parmenter, B Haselkorn, JK Lovera, JF Bourdette, D Turner, AP AF Hughes, Abbey J. Hartoonian, Narineh Parmenter, Brett Haselkorn, Jodie K. Lovera, Jesus F. Bourdette, Dennis Turner, Aaron P. TI Cognitive Impairment and Community Integration Outcomes in Individuals Living With Multiple Sclerosis SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Community integration; Multiple sclerosis; Neurobehavioral manifestations; Rehabilitation ID QUALITY-OF-LIFE; TRAUMATIC BRAIN-INJURY; INFORMATION-PROCESSING SPEED; BECK DEPRESSION INVENTORY; FATIGUE SEVERITY SCALE; MEMORY IMPAIRMENT; GINKGO-BILOBA; QUESTIONNAIRE; DISABILITY; VALIDITY AB Objectives: To determine the association between unique domains of cognitive impairment and community integration in individuals with multiple sclerosis (MS), and to determine the contributions of cognitive impairment to community integration beyond the influence of demographic and clinical variables. Design: Cross-sectional analysis of objective neuropsychological assessment and self-report data. Data were collected during baseline assessment of a randomized, multisite controlled trial of ginkgo biloba for cognitive impairment in MS. Hierarchical regression analyses examined the association between subjective and objective measures of cognitive impairment and 3 domains of community integration, adjusting for relevant covariates. Setting: Two Veterans Affairs medical center MS clinics. Participants: Adults (N = 121; ages 24-65y) with a confirmed MS diagnosis. Interventions: Not applicable. Main Outcome Measures: Primary outcomes were scores on the Home Integration (CIQ-H), Social Integration (CIQ-S), and Productivity (CIQ-P) domains of the Community Integration Questionnaire (CIQ). Results: Cognitive impairment was associated with lower scores on the CIQ-H and CIQ-S, but not the CIQ-P. Greater levels of subjective cognitive impairment were associated with lower scores on the CIQ-H and CIQ-S. Greater levels of objective cognitive impairment, specifically slower processing speed and poorer inhibitory control, were related to lower CIQ-S scores. Subjective and objective measures of cognitive impairment were significantly and independently associated with CIQ-S. Conclusions: Objective cognitive impairment may interfere with participation in social activities. Subjective cognitive impairment is also important to assess, because individuals who perceive themselves to be cognitively impaired may be less likely to participate in both home and social activities. Clinical interventions to enhance community integration in individuals with MS may benefit from addressing objective and subjective cognitive impairment by integrating cognitive rehabilitation approaches with self-efficacy enhancing strategies. (C) 2015 by the American Congress of Rehabilitation Medicine C1 [Hughes, Abbey J.; Hartoonian, Narineh; Haselkorn, Jodie K.; Turner, Aaron P.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Multiple Sclerosis Ctr Excellence West, Seattle, WA USA. [Hughes, Abbey J.; Haselkorn, Jodie K.; Turner, Aaron P.] Univ Washington, Dept Rehabil Med, Seattle, WA 98104 USA. [Parmenter, Brett] Vet Affairs Puget Sound Hlth Care Syst, Amer Lake Div, Tacoma, WA USA. [Haselkorn, Jodie K.] Univ Washington, Dept Epidemiol, Seattle, WA 98104 USA. [Lovera, Jesus F.] Louisiana State Univ, Hlth Sci Ctr, Dept Neurol, New Orleans, LA USA. [Bourdette, Dennis] Vet Affairs Portland Hlth Care Syst, Multiple Sclerosis Ctr Excellence West, Portland, OR USA. [Bourdette, Dennis] Oregon Hlth & Sci Univ, Dept Neurol, Sch Med, Portland, OR 97201 USA. RP Hughes, AJ (reprint author), Univ Washington, Dept Rehabil Med, 325 Ninth Ave,Box 359612, Seattle, WA 98104 USA. EM ajhughes@uw.edu RI Hughes, Abbey/K-8861-2015 OI Hughes, Abbey/0000-0002-7612-6887 FU Department of Veterans Affairs, Office of Research and Development, Rehabilitation Research and Development [B4368R]; National Multiple Sclerosis Society [MB 0026] FX Supported by the Department of Veterans Affairs, Office of Research and Development, Rehabilitation Research and Development (grant no. B4368R), and by a mentor-based fellowship grant from the National Multiple Sclerosis Society (grant no. MB 0026). The contents of this paper do not represent the view of the Department of Veterans Affairs of the U.S. Government. NR 52 TC 2 Z9 2 U1 1 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 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD NOV PY 2015 VL 96 IS 11 BP 1973 EP 1979 DI 10.1016/j.apmr.2015.07.003 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA DB1YX UT WOS:000368306600005 PM 26189203 ER PT J AU Sawyer, K Bell, KR Ehde, DM Temkin, N Dikmen, S Williams, RM Dillworth, T Hoffman, JM AF Sawyer, Kathryn Bell, Kathleen R. Ehde, Dawn M. Temkin, Nancy Dikmen, Sureyya Williams, Rhonda M. Dillworth, Tiara Hoffman, Jeanne M. TI Longitudinal Study of Headache Trajectories in the Year After Mild Traumatic Brain Injury: Relation to Posttraumatic Stress Disorder Symptoms SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Headache; Rehabilitation; Stress disorders; post-traumatic ID COMORBID CHRONIC PAIN; US SOLDIERS; VETERANS; PTSD; DEPRESSION; SEVERITY; MODERATE; HEALTH AB Objective: To examine headache trajectories among persons with mild traumatic brain injury (MTBI) in the year after injury and the relation of headache trajectory to posttraumatic stress disorder (PTSD) at 1 year postinjury. Design: Prospective, longitudinal study. Setting: Participants were recruited through a university medical center and participated in follow-up assessments by telephone. Participants: Prospectively enrolled individuals (N=212) within 1 week of MTBI who were hospitalized for observation or other system injuries. Participants were assessed at baseline and 3, 6, and 12 months postinjury. Interventions: Not applicable. Main Outcome Measures: Participants rated average headache pain intensity using the 0 to 10 numerical rating scale at each assessment period. The PTSD Checklist-Civilian Version was completed at 12 months postinjury. Results: Latent class growth analysis produced a 4-trajectory group model, with groups labeled resolved, worsening, improving, and chronic. Multivariate regression modeling revealed that younger age and premorbid headache correlated with membership in the worse trajectory groups (worsening and chronic; P<.001). Univariate regression revealed a significant association between PTSD and membership in the worse trajectory groups (P<.001). Conclusions: Headache is common in the year after MTBI, with younger people, persons who previously had headaches, and persons with PTSD more likely to report chronic or worsening headache. Further research is needed to examine whether PTSD symptoms exacerbate headaches or whether problematic headache symptoms exacerbate PTSD. (C) 2015 by the American Congress of Rehabilitation Medicine C1 [Sawyer, Kathryn; Ehde, Dawn M.; Temkin, Nancy; Dikmen, Sureyya; Williams, Rhonda M.; Dillworth, Tiara; Hoffman, Jeanne M.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Bell, Kathleen R.] Univ Texas SW Med Ctr Dallas, Dept Phys Med & Rehabil, Dallas, TX 75390 USA. [Temkin, Nancy; Dikmen, Sureyya] Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA. [Temkin, Nancy] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Dikmen, Sureyya] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Williams, Rhonda M.] Vet Affairs Puget Sound Healthcare Syst, Seattle, WA USA. RP Sawyer, K (reprint author), Univ Washington, Sch Med, Box 359612, Seattle, WA 98195 USA. EM kasawyer@uw.edu FU Department of Education, National Institute on Disability and Rehabilitation Research [H133G090022]; Department of Defense Congressionally Directed Medical Research Programs [W81XWH-12-2-0109] FX Supported by the Department of Education, National Institute on Disability and Rehabilitation Research (grant no. H133G090022) and Department of Defense Congressionally Directed Medical Research Programs (grant no. W81XWH-12-2-0109). NR 32 TC 2 Z9 2 U1 1 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 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD NOV PY 2015 VL 96 IS 11 BP 2000 EP 2006 DI 10.1016/j.apmr.2015.07.006 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA DB1YX UT WOS:000368306600009 PM 26220236 ER PT J AU Huang, W Wang, B Li, XY Kang, JX AF Huang, Wei Wang, Bin Li, Xiangyong Kang, Jing X. TI Endogenously elevated n-3 polyunsaturated fatty acids alleviate acute ethanol-induced liver steatosis SO BIOFACTORS LA English DT Article DE n-3 PUFA; alcoholic liver steatosis; fat-1 mice; lipid metabolism; oxidative stress ID HEPATIC STEATOSIS; DISEASE PATHOGENESIS; LIPID-PEROXIDATION; OXIDATIVE STRESS; GENE-EXPRESSION; TRANSGENIC MICE; FAT-1 MICE; TNF-ALPHA; OMEGA-3-FATTY-ACIDS; ACTIVATION AB Effective means for the prevention of alcohol-induced liver disease, a global health problem, have yet to be developed. We evaluated whether the high endogenous levels of omega-3 polyunsaturated acids (n-3 PUFA) in fat-1 transgenic mice could protect them against acute ethanol-induced liver steatosis. We induced alcoholic liver steatosis in 9-week-old male heterozygous fat-1 mice and their wild-type (WT) male littermates through three oral gavages of 60% ethanol at 4.7 g/kg body weight. Hepatic lipid accumulation was significantly increased in both alcohol treatment groups, but by much less in the fat-1 group compared with the WT group. Fat-1 mice exhibited significantly lower levels of total hepatic/plasma TG and plasma alanine aminotransferase activity. Accordingly, hepatic expression of lipogenesis-related genes (e.g., SREBP-1c, FAS, and SCD-1) and plasma levels of inflammatory cytokines (e.g., IL-6, TNF-alpha, and MCP-1) were reduced in the fat-1 mice. Furthermore, decreased hepatic expression of cytochrome P450 2E1 (CYP2E1) and increased hepatic levels of PPAR-alpha and HO-1 were observed in the fat-1 mice, compared to the WT mice. These findings show that elevated tissue n-3 PUFA protect against acute ethanol-induced liver steatosis in fat-1 mice, possibly through the down-regulation of hepatic lipogenesis, inflammatory response, and oxidative stress. (c) 2015 BioFactors, 41(6):453-462, 2015 C1 [Huang, Wei; Wang, Bin; Li, Xiangyong; Kang, Jing X.] Massachusetts Gen Hosp, Lab Lipid Med & Technol, Dept Med, Boston, MA 02129 USA. [Huang, Wei; Wang, Bin; Li, Xiangyong; Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA USA. [Huang, Wei] Third Mil Med Univ, Biomed Anal Ctr, Chongqing, Peoples R China. [Wang, Bin] Third Mil Med Univ, Inst Mil Prevent Med, Res Ctr Nutr & Food Safety, Chongqing, Peoples R China. RP Kang, JX (reprint author), Massachusetts Gen Hosp, Lab Lipid Med & Technol, 149-13th St,Room 4001, Boston, MA 02129 USA. EM kang.jing@mgh.harvard.edu FU Sansun Life Sciences; Fortune Education Foundation FX This study was supported by the generous funding from Sansun Life Sciences and the Fortune Education Foundation. The authors are also grateful to Marina Kang for her editorial assistance. NR 44 TC 2 Z9 2 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0951-6433 EI 1872-8081 J9 BIOFACTORS JI Biofactors PD NOV-DEC PY 2015 VL 41 IS 6 BP 453 EP 462 DI 10.1002/biof.1246 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA DB0JJ UT WOS:000368194100008 PM 26637972 ER PT J AU Satwani, P Ahn, KW Carreras, J Abdel-Azim, H Cairo, MS Cashen, A Chen, AI Cohen, JB Costa, LJ Dandoy, C Fenske, TS Freytes, CO Ganguly, S Gale, RP Ghosh, N Hertzberg, MS Hayashi, RJ Kamble, RT Kanate, AS Keating, A Kharfan-Dabaja, MA Lazarus, HM Marks, DI Nishihori, T Olsson, RF Prestidge, TD Rolon, JM Savani, BN Vose, JM Wood, WA Inwards, DJ Bachanova, V Smith, SM Maloney, DG Sureda, A Hamadani, M AF Satwani, P. Ahn, K. W. Carreras, J. Abdel-Azim, H. Cairo, M. S. Cashen, A. Chen, A. I. Cohen, J. B. Costa, L. J. Dandoy, C. Fenske, T. S. Freytes, C. O. Ganguly, S. Gale, R. P. Ghosh, N. Hertzberg, M. S. Hayashi, R. J. Kamble, R. T. Kanate, A. S. Keating, A. Kharfan-Dabaja, M. A. Lazarus, H. M. Marks, D. I. Nishihori, T. Olsson, R. F. Prestidge, T. D. Rolon, J. M. Savani, B. N. Vose, J. M. Wood, W. A. Inwards, D. J. Bachanova, V. Smith, S. M. Maloney, D. G. Sureda, A. Hamadani, M. TI A prognostic model predicting autologous transplantation outcomes in children, adolescents and young adults with Hodgkin lymphoma SO BONE MARROW TRANSPLANTATION LA English DT Article ID STEM-CELL TRANSPLANTATION; HIGH-DOSE CHEMOTHERAPY; EVENT-FREE SURVIVAL; SALVAGE THERAPY; CONDITIONING REGIMEN; DISEASE; INTENSITY; RECURRENT; CYCLOPHOSPHAMIDE; MANAGEMENT AB Autologous hematopoietic cell transplantation (AutoHCT) is a potentially curative treatment modality for relapsed/ refractory Hodgkin lymphoma (HL). However, no large studies have evaluated pretransplant factors predictive of outcomes of AutoHCT in children, adolescents and young adults (CAYA, age < 30 years). In a retrospective study, we analyzed 606 CAYA patients (median age 23 years) with relapsed/refractory HL who underwent AutoHCT between 1995 and 2010. The probabilities of PFS at 1, 5 and 10 years were 66% (95% confidence interval (CI): 62-70), 52% (95% CI: 48-57) and 47% (95% CI: 42-51), respectively. Multivariate analysis for PFS demonstrated that at the time of AutoHCT patients with Karnofsky/Lansky score >= 90, no extranodal involvement and chemosensitive disease had significantly improved PFS. Patients with time from diagnosis to first relapse of < 1 year had a significantly inferior PFS. A prognostic model for PFS was developed that stratified patients into low-, intermediate-and high-risk groups, predicting for 5-year PFS probabilities of 72% (95% CI: 64-80), 53% (95% CI: 47-59) and 23% (95% CI: 9-36), respectively. This large study identifies a group of CAYA patients with relapsed/refractory HL who are at high risk of progression after AutoHCT. Such patients should be targeted for novel therapeutic and/or maintenance approaches post-AutoHCT. C1 [Satwani, P.] Columbia Univ, Dept Pediat, Med Ctr, Div Pediat Hematol Oncol & Stem Cell Transplantat, New York, NY 10027 USA. [Ahn, K. W.; Carreras, J.; Hamadani, M.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Ahn, K. W.] Med Coll Wisconsin, Inst Hlth & Soc, Div Biostat, Milwaukee, WI 53226 USA. [Abdel-Azim, H.] Univ So Calif, Keck Sch Med, Childrens Hosp Los Angeles, Div Hematol Oncol & Blood & Marrow Transplantat, Los Angeles, CA 90033 USA. [Cairo, M. S.] New York Med Coll, Pediat Hematol Oncol & Stem Cell Transplantat, New York, NY USA. [Cashen, A.] Washington Univ, Sch Med, Div Oncol, St Louis, MO USA. [Chen, A. I.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Cohen, J. B.] Emory Univ, Sch Med, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA USA. [Costa, L. J.] Univ Alabama Birmingham, Dept Med, Div Hematol Oncol, Birmingham, AL 35294 USA. [Dandoy, C.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Fenske, T. S.] Med Coll Wisconsin, Div Hematol & Oncol, Milwaukee, WI 53226 USA. [Freytes, C. O.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Freytes, C. O.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Ganguly, S.] Univ Kansas, Med Ctr, Div Hematol & Oncol, Blood & Marrow Transplantat, Kansas City, KS 66103 USA. [Gale, R. P.] Univ London Imperial Coll Sci Technol & Med, Dept Med, Div Expt Med, Hematol Res Ctr, London, England. [Ghosh, N.] Carolinas Healthcare Syst, Levine Canc Inst, Dept Hematol Oncol & Blood Disorders, Charlotte, NC USA. [Hertzberg, M. S.] Prince Wales Hosp, Dept Haematol, Randwick, NSW 2031, Australia. [Hayashi, R. J.] Washington Univ, Dept Pediat, Sch Med St Louis, Div Pediat Hematol Oncol, St Louis, MO 63130 USA. [Kamble, R. T.] Baylor Coll Med, Ctr Cell & Gene Therapy, Div Hematol & Oncol, Houston, TX 77030 USA. [Kanate, A. S.] W Virginia Univ, Osborn Hematopoiet Malignancy & Transplantat Prog, Morgantown, WV 26506 USA. [Kharfan-Dabaja, M. A.; Nishihori, T.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL 33612 USA. [Lazarus, H. M.] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Cleveland, OH USA. [Marks, D. I.] Univ Hosp Bristol NHS Trust, Pediat Bone Marrow Transplant, Bristol, Avon, England. [Olsson, R. F.] Karolinska Inst, Dept Lab Med, Div Therapeut Immunol, Stockholm, Sweden. [Olsson, R. F.] Uppsala Univ, Ctr Clin Res Sormland, Uppsala, Sweden. [Prestidge, T. D.] Starship Childrens Hosp, Blood & Canc Ctr, Auckland, New Zealand. [Rolon, J. M.] FUNDALEU, Bone Marrow Transplante Unit, Buenos Aires, DF, Argentina. [Savani, B. N.] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, Nashville, TN 37235 USA. [Vose, J. M.] Nebraska Med Ctr, Dept Internal Med, Omaha, NE USA. [Wood, W. A.] Univ N Carolina, Dept Med, Div Hematol Oncol, Chapel Hill, NC USA. [Inwards, D. J.] Mayo Clin, Div Hematol, Rochester, MN USA. [Bachanova, V.] Univ Minnesota, Med Ctr, Bone & Marrow Transplant Program, Minneapolis, MN 55455 USA. [Smith, S. M.] Univ Chicago, Sect Hematol Oncol, Chicago, IL 60637 USA. [Maloney, D. G.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Sureda, A.] Hosp Duran & Reynals, Inst Catala Oncol, Serv Hematol, Barcelona, Spain. RP Hamadani, M (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, 9200W Wisconsin Ave,Suite C5500, Milwaukee, WI 53226 USA. EM mhamadani@mcw.edu FU Public Health Service from the National Cancer Institute (NCI) [U24-CA076518]; National Heart, Lung and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases (NIAID); NHLBI [5U10HL069294]; NCI; Health Resources and Services Administration (HRSA/DHHS) [HHSH250201200016C]; Office of Naval Research [N00014-12-1-0142, N00014-13-1-0039]; Actinium Pharmaceuticals; Allos Therapeutics, Inc.; Amgen, Inc.; Ariad; Be the Match Foundation; Blue Cross and Blue Shield Association; Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc.; Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; Leukemia & Lymphoma Society; Medac GmbH; Medical College of Wisconsin; Merck Co, Inc.; Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; Remedy Informatics; Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix Pharmaceuticals; TerumoBCT; Teva Neuroscience, Inc.; THERAKOS, Inc.; University of Minnesota; University of Utah; Wellpoint, Inc. FX We thank the patients and centers reporting to CIBMTR and CIBMTR Lymphoma. We also thank the following committee members for their scientific input: Baldeep Wirk, Basem M William, Harry C Schouten, Nishitha M Reddy, David Rizzieri, Mahmoud Aljurf, Reinhold Munker, Brandon Hayes-Lattin, Victor A Lewis, and Maggie M Simaytis for administrative support. The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U10HL069294 from NHLBI and NCI; a contract HHSH250201200016C with Health Resources and Services Administration (HRSA/DHHS); two Grants N00014-12-1-0142 and N00014-13-1-0039 from the Office of Naval Research; and grants from *Actinium Pharmaceuticals; Allos Therapeutics, Inc.; *Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Ariad; Be the Match Foundation; *Blue Cross and Blue Shield Association; *Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America, Inc.; *Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; *Gentium SpA; Genzyme Corporation; GlaxoSmithKline; Health Research, Inc.; Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH; The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The Takeda Oncology Co.; *Milliman USA, Inc.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Perkin Elmer, Inc.; *Remedy Informatics; *Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.; Stemsoft Software, Inc.; Swedish Orphan Biovitrum; *Tarix Pharmaceuticals; *TerumoBCT; *Teva Neuroscience, Inc.; *THERAKOS, Inc.; University of Minnesota; University of Utah; and *Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration (HRSA) or any other agency of the US Government. *Corporate Members. NR 38 TC 4 Z9 4 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 EI 1476-5365 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD NOV PY 2015 VL 50 IS 11 BP 1416 EP 1423 DI 10.1038/bmt.2015.177 PG 8 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA DB1PU UT WOS:000368281800004 PM 26237164 ER PT J AU Thibaut, A Di Perri, C Chatelle, C Bruno, MA Bahri, MA Wannez, S Piarulli, A Bernard, C Martial, C Heine, L Hustinx, R Laureys, S AF Thibaut, Aurore Di Perri, Carol Chatelle, Camille Bruno, Marie-Aurelie Bahri, Mohamed Ali Wannez, Sarah Piarulli, Andrea Bernard, Claire Martial, Charlotte Heine, Lizette Hustinx, Roland Laureys, Steven TI Clinical Response to tDCS Depends on Residual Brain Metabolism and Grey Matter Integrity in Patients With Minimally Conscious State SO BRAIN STIMULATION LA English DT Article DE Transcranial direct current stimulation; Disorders of consciousness; Treatment; Magnetic resonance imaging; Voxel-based morphometry; Positron emission tomography; Minimally conscious state ID DIRECT-CURRENT STIMULATION; VOXEL-BASED MORPHOMETRY; HUMAN MOTOR CORTEX; TRANSCRANIAL DC-STIMULATION; VEGETATIVE STATE; WORKING-MEMORY; PARKINSONS-DISEASE; DAMAGED PATIENTS; FUNCTIONAL MRI; CONNECTIVITY AB Background: Transcranial direct current stimulation (tDCS) was recently shown to promote recovery of voluntary signs of consciousness in some patients in minimally conscious state (MCS). However, it remains unclear why clinical improvement is only observed in a subgroup of patients. Objectives: In this retrospective study, we investigated the relationship between tDCS responsiveness and neuroimaging data from MCS patients. Methods: Structural Magnetic Resonance Imaging (MRI), Fluorodeoxyglucose Positron emission tomography (FDG-PET) and clinical electroencephalography (EEG) were acquired in 21 sub-acute and chronic MCS patients (8 tDCS responders) who subsequently (<48 h) received left dorsolateral prefrontal (DLPF) tDCS in a double-blind randomized cross-over trial. The behavioral data have been published elsewhere (Thibaut et al., Neurology, 2014). Results: Grey matter atrophy was observed in non-responders as compared with responders in the left DLPF cortex, the medial-prefrontal cortex, the cingulate cortex, the hippocampi, part of the rolandic regions, and the left thalamus. FDG-PET showed hypometabolism in non-responders as compared with responders in the left DLPF cortex, the medial-prefrontal cortex, the precuneus, and the thalamus. EEG did not show any difference between the two groups. Conclusion: Our findings suggest that the transient increase of signs of consciousness following left DLPF tDCS in patients in MCS require grey matter preservation and residual metabolic activity in cortical and subcortical brain areas known to be involved in attention and working memory. These results further underline the critical role of long-range cortico-thalamic connections in consciousness recovery, providing important information for guidelines on the use of tDCS in disorders of consciousness. (C) 2015 Elsevier Inc. All rights reserved. C1 [Thibaut, Aurore; Di Perri, Carol; Bruno, Marie-Aurelie; Wannez, Sarah; Piarulli, Andrea; Martial, Charlotte; Heine, Lizette; Laureys, Steven] GIGA Res, Cyclotron Res Ctr, Coma Sci Grp, B-4000 Liege, Belgium. [Thibaut, Aurore; Di Perri, Carol; Bruno, Marie-Aurelie; Wannez, Sarah; Piarulli, Andrea; Martial, Charlotte; Heine, Lizette; Laureys, Steven] Univ & Univ Hosp Liege, Dept Neurol, Liege, Belgium. [Chatelle, Camille] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Neurorehabil Lab,Dept Phys Med & Rehabil, Boston, MA USA. [Chatelle, Camille] Massachusetts Gen Hosp, Lab NeuroImaging Coma & Consciousness, Boston, MA 02114 USA. [Bahri, Mohamed Ali] Univ Liege, Cyclotron Res Ctr, Liege, Belgium. [Piarulli, Andrea] Scuola Normale Super Pisa, PERCRO Lab, Pisa, Italy. [Bernard, Claire; Hustinx, Roland] Univ Hosp Liege, Dept Nucl Med, Liege, Belgium. RP Thibaut, A (reprint author), GIGA Res, Cyclotron Res Ctr, Coma Sci Grp, Ave Hop 1, B-4000 Liege, Belgium. EM athibaut@ulg.ac.be RI Laureys, Steven/A-3349-2011; OI Martial, Charlotte/0000-0001-6291-3460 FU National Funds for Scientific Research (FNRS); Action de Recherche Concertee (ARC); Fonds Leon Fredericq; James S. McDonnell Foundation; Mind Science Foundation; University of Liege; Belgian American Educational Foundation (BAEF); Federation Wallonie Bruxelles International (WBI); Belgian interuniversity attraction pole FX This study was supported by the National Funds for Scientific Research (FNRS), Action de Recherche Concertee (ARC), Fonds Leon Fredericq, James S. McDonnell Foundation, Mind Science Foundation, University of Liege, the Belgian American Educational Foundation (BAEF), the Federation Wallonie Bruxelles International (WBI) and the Belgian interuniversity attraction pole. NR 70 TC 4 Z9 4 U1 2 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1935-861X EI 1876-4754 J9 BRAIN STIMUL JI Brain Stimul. PD NOV-DEC PY 2015 VL 8 IS 6 BP 1116 EP 1123 DI 10.1016/j.brs.2015.07.024 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DA8WO UT WOS:000368087700015 PM 26471400 ER PT J AU Lai, PS Sheehan, WJ Gaffin, JM Petty, CR Coull, BA Gold, DR Phipatanakul, W AF Lai, Peggy S. Sheehan, William J. Gaffin, Jonathan M. Petty, Carter R. Coull, Brent A. Gold, Diane R. Phipatanakul, Wanda TI School Endotoxin Exposure and Asthma Morbidity in Inner-city Children SO CHEST LA English DT Article ID ION-CHARGING DEVICE; AIRBORNE ALLERGENS; DESIGN; DUST; HEALTH; HOMES AB BACKGROUND: Endotoxin exposure is associated with airway inflammation. Children spend 6 to 8 h/d in school, yet the effect of school-specific endotoxin exposure on asthma morbidity is not well understood. METHODS: In this longitudinal cohort study, 248 students with asthma, from 38 inner-city schools, underwent baseline phenotyping and follow-up. Clinical outcomes were evaluated throughout the academic school year and linked to classroom-specific dust and air endotoxin levels as well as home dust endotoxin levels. The primary outcome was maximum asthma symptom-days per 2-week period. RESULTS: Classrooms had higher settled dust endotoxin levels compared with homes (14.3 endotoxin unit/mg vs 11.3 endotoxin unit/mg; P = .02), Airborne endotoxin levels exceeding recommended occupational exposure limits for adults were recorded in 22.0% of classrooms. Classroom air endotoxin levels were independently associated with increased maximum symptom-days in children with nonatopic asthma, but not in those with atopic asthma (interaction P = .03). Adjusting for home exposures, classroom endotoxin exposure was independently associated with a dose-dependent increase in asthma symptom-days for children with nonatopic asthma (adjusted incidence rate ratio, 1.16 [95% CI, 1,03-1.311; P = .02). In these subjects, maximum symptom-days increased by 1,3 days for each 14-day period when comparing students in classrooms with the lowest endotoxin levels compared with average measured levels. CONCLUSIONS: Inner-city children with asthma are exposed to high levels of airborne endotoxin at school, resulting in increased asthma symptoms in children with nonatopic asthma. Mitigation of school-related exposures may represent a strategy to decrease asthma morbidity in this population. C1 [Lai, Peggy S.] Massachusetts Gen Hosp, Div Pulm & Crit Care, Boston, MA 02114 USA. [Lai, Peggy S.; Gold, Diane R.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Coull, Brent A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Lai, Peggy S.; Sheehan, William J.; Gaffin, Jonathan M.; Gold, Diane R.; Phipatanakul, Wanda] Harvard Univ, Sch Med, Boston Childrens Hosp, Boston, MA USA. [Sheehan, William J.; Gaffin, Jonathan M.; Petty, Carter R.; Gold, Diane R.; Phipatanakul, Wanda] Boston Childrens Hosp, Boston, MA 02115 USA. [Gold, Diane R.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. RP Phipatanakul, W (reprint author), Boston Childrens Hosp, Div Immunol & Allergy, 300 Longwood Ave,Fegan 6, Boston, MA 02115 USA. EM wanda.phipatanakul@childrens.harvard.edu FU US National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases [U01 AI 110397, R01 AI 073964, K24 AI 106822, K23 AI104780, K23 AI106945]; NIH National Institute of Environmental Health Sciences [K23ES023700, P30 ES000002]; Harvard Catalyst/The Harvard Clinical and Translational Science Center [NIH] [8UL1TR000170]; American College of Allergy, Asthma, and Immunology Young Faculty Award; Division of Immunology Clinical Research Advisory Group Research Grant; American Lung Association/American Academy of Allergy, Asthma, and Immunology Respiratory Diseases Faculty Award; Deborah Munroe Noonan Memorial Award FX This study was funded by US National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases [U01 AI 110397, R01 AI 073964, K24 AI 106822, K23 AI104780, and K23 AI106945] and NIH National Institute of Environmental Health Sciences [K23ES023700 and P30 ES000002]. This work was also conducted with support from Harvard Catalyst/The Harvard Clinical and Translational Science Center [NIH award 8UL1TR000170]; American College of Allergy, Asthma, and Immunology Young Faculty Award; Division of Immunology Clinical Research Advisory Group Research Grant; American Lung Association/American Academy of Allergy, Asthma, and Immunology Respiratory Diseases Faculty Award; and the Deborah Munroe Noonan Memorial Award. NR 26 TC 6 Z9 6 U1 1 U2 5 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 2015 VL 148 IS 5 BP 1251 EP 1258 DI 10.1378/chest.15-0098 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DB1MZ UT WOS:000368273600034 PM 26087201 ER PT J AU Chaddha, A Eagle, KA Braverman, AC Kline-Rogers, E Hirsch, AT Brook, R Jackson, EA Woznicki, EM Housholder-Hughes, S Pitler, L Franklin, BA AF Chaddha, Ashish Eagle, Kim A. Braverman, Alan C. Kline-Rogers, Eva Hirsch, Alan T. Brook, Robert Jackson, Elizabeth A. Woznicki, Elise M. Housholder-Hughes, Susan Pitler, Linda Franklin, Barry A. TI Exercise and Physical Activity for the Post-Aortic Dissection Patient: The Clinician's Conundrum SO CLINICAL CARDIOLOGY LA English DT Editorial Material ID ACUTE AORTIC DISSECTION; LONG-TERM SURVIVAL; BLOOD-PRESSURE; PROPRANOLOL; METOPROLOL; REPAIR; REST; COMBINATION; REGISTRY; BLOCKER AB Despite the paucity of evidence, it is often presumed, and is physiologically plausible, that sudden, acute elevations in blood pressure may transiently increase the risk of recurrent aortic dissection (AD) or rupture in patients with a prior AD, because a post-dissection aorta is almost invariably dilated and may thus experience greater associated wall stress as compared with a nondilated aorta. Few data are available regarding the specific types and intensities of exercise that may be both safe and beneficial for this escalating patient population. The purpose of this editorial/commentary is to further explore this conundrum for clinicians caring for and counseling AD survivors. Moderate-intensity cardiovascular activity may be cardioprotective in this patient cohort. It is likely that severe physical activity restrictions may reduce functional capacity and quality of life in post-AD patients and thus be harmful, underscoring the importance of further exploring the role of physical activity and/or structured exercise in this at-risk patient population. C1 [Chaddha, Ashish; Eagle, Kim A.; Kline-Rogers, Eva; Jackson, Elizabeth A.; Woznicki, Elise M.; Housholder-Hughes, Susan] Univ Michigan, Ctr Cardiovasc, Ann Arbor, MI 48106 USA. [Braverman, Alan C.] Washington Univ, Div Cardiovasc, St Louis, MO USA. [Pitler, Linda] Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA 02114 USA. [Hirsch, Alan T.] Univ Minnesota Phys Heart Practice, Div Cardiovasc, Minneapolis, MN USA. [Franklin, Barry A.] William Beaumont Hosp, Beaumont Hlth Ctr, Prevent Cardiol & Cardiac Rehabil, Royal Oak, MI 48072 USA. RP Chaddha, A (reprint author), Univ Michigan, Ctr Cardiovasc, Michigan Cardiovasc Outcomes Res & Reporting Prog, 24 Frank Lloyd Wright Dr,Lobby A-3201, Ann Arbor, MI 48106 USA. EM achaddha@umich.edu NR 30 TC 2 Z9 2 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0160-9289 EI 1932-8737 J9 CLIN CARDIOL JI Clin. Cardiol. PD NOV PY 2015 VL 38 IS 11 BP 647 EP 651 DI 10.1002/clc.22481 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DB1OR UT WOS:000368278500002 PM 26769698 ER PT J AU Ducroq, G Schulte, PJ Becker, RC Cannon, CP Hanington, RA Held, C Himmelmann, A Lassila, R Storey, RF Sorbets, E Wallentin, L Steg, PG AF Ducroq, Gregory Schulte, Phillip J. Becker, Richard C. Cannon, Christopher P. Hanington, Robert A. Held, Claes Himmelmann, Anders Lassila, Riitta Storey, Robert F. Sorbets, Emmanuel Wallentin, Lars Steg, Philippe Gabriel TI Association of spontaneous and procedure-related bleeds with short- and long-term mortality after acute coronary syndromes: an analysis from the PLATO trial SO EUROINTERVENTION LA English DT Article DE acute coronary syndromes; haemorrhage; mortality ID ELEVATION MYOCARDIAL-INFARCTION; ACADEMIC RESEARCH CONSORTIUM; TRITON-TIMI 38; RANDOMIZED EVALUATION; PLATELET INHIBITION; CLINICAL-OUTCOMES; PROGNOSTIC VALUE; INTERVENTION; IMPACT; CLOPIDOGREL AB Aims: We sought to describe the differential effect of bleeding events in acute coronary syndromes (ACS) on short- and long-term mortality according to their type and severity. Methods and results: The PLATO trial randomised 18,624 ACS patients to clopidogrel or ticagrelor. Post-randomisation bleeding events were captured according to bleeding type (spontaneous or procedure-related), with PLATO, TIMI, and GUSTO definitions. The association of bleeding events with subsequent short-term (<30 days) and long-term (>30 days) all-cause mortality was assessed using time-dependent Cox proportional hazard models. A model was fitted to compare major and minor bleeding for mortality prediction. Of 18,624 patients, 2,189 (11.8%) had at least one PLATO major bleed (mean follow-up 272.2 +/- 123.5 days). Major bleeding was associated with higher short-term mortality (adjusted hazard ratio [HR] 9.28; 95% confidence interval [CI]: 7.50-11.48) but not with long-term mortality (adjusted HR 1.28; 95% CI: 0.93-1.75). Spontaneous bleeding was associated with short-term (adjusted HR 14.59; 95% CI: 11.14-19.11) and long-term (adjusted HR 3.38; 95% CI: 2.26-5.05) mortality. Procedure-related bleeding was associated with short-term mortality (adjusted HR 5.29; 95% CI: 4.06-6.87): CABG-related and non-coronary-procedure-related bleeding were associated with a higher short-term mortality, whereas PCI or angiography-related bleeding was not associated with either short- or long-term mortality. Similar results were obtained using the GUSTO and TIMI bleeding definitions. Conclusions: Major bleeding is associated with high subsequent mortality in ACS. However, this association is much stronger in the first 30 days and is strongest for spontaneous (vs. procedure-related) bleeding. C1 [Ducroq, Gregory; Steg, Philippe Gabriel] Hop Bichat Claude Bernard, Dept Hosp Univ FIRE, AP HP, F-75018 Paris, France. [Ducroq, Gregory; Sorbets, Emmanuel; Steg, Philippe Gabriel] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France. [Ducroq, Gregory; Steg, Philippe Gabriel] INSERM, U1148, Paris, France. [Schulte, Phillip J.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Becker, Richard C.] Acad Hlth Ctr, Heart Lung & Vasc Inst, Div Cardiovas Hlth & Dis, Cincinnati, OH USA. [Cannon, Christopher P.] Brigham & Womens Hosp, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA. [Cannon, Christopher P.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hanington, Robert A.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Held, Claes; Wallentin, Lars] Uppsala Univ, Dept Med Sci, Cardiol & Uppsala Clin Res Ctr, Uppsala, Sweden. [Himmelmann, Anders] AstraZeneca Res & Dev, Molndal, Sweden. [Lassila, Riitta] Univ Helsinki, Cent Hosp, Coagulat Disorders, Div Hematol & Lab Serv, Helsinki, Finland. [Storey, Robert F.] Univ Sheffield, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England. [Sorbets, Emmanuel] Hop Bichat Claude Bernard, AP HP, Nucl Med Serv, F-75018 Paris, France. [Steg, Philippe Gabriel] Univ London Imperial Coll Sci Technol & Med, Royal Brompton Hosp, ICMS, NHLI, London, England. RP Steg, PG (reprint author), Hop Bichat Claude Bernard, 46 Rue Henri Huchard, F-75018 Paris, France. EM gabriel.steg@bch.aphp.fr FU AstraZeneca FX Editorial support was provided by Sophie Rushton-Smith, PhD (MedLink Healthcare Communications), and was funded by the authors. Publication management was provided by Ebba Bergman, PhD (Uppsala Clinical Research Center), and was funded by AstraZeneca. NR 24 TC 8 Z9 8 U1 0 U2 0 PU EUROPA EDITION PI TOULOUSE CEDEX 6 PA 19 ALLEES JEAN JAURES B P 61508, TOULOUSE CEDEX 6, 31015, FRANCE SN 1774-024X EI 1969-6213 J9 EUROINTERVENTION JI EuroIntervention PD NOV PY 2015 VL 11 IS 7 BP 737 EP 745 DI 10.4244/EIJY14M09_11 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DB0RB UT WOS:000368214100005 PM 25254357 ER PT J AU Yee, KMP Feener, EP Madigan, M Jackson, NJ Gao, BB Ross-Cisneros, FN Provis, J Aiello, LP Sadun, AA Sebag, J AF Yee, Kenneth M. P. Feener, Edward P. Madigan, Michele Jackson, Nicholas J. Gao, Ben-Bo Ross-Cisneros, Fred N. Provis, Jan Aiello, Lloyd Paul Sadun, Alfredo A. Sebag, J. TI Proteomic Analysis of Embryonic and Young Human Vitreous SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE vitreous; proteomics; embryology; vascular development ID PROLIFERATIVE DIABETIC-RETINOPATHY; VASCULAR SYSTEM REGRESSION; MASS-SPECTROMETRY; VITREORETINAL DISEASES; GEL-ELECTROPHORESIS; SOLUBLE-PROTEINS; ANGIOGENESIS; NEOVASCULARIZATION; CATALOG; MODEL AB PURPOSE. The proteomic profile of vitreous from second-trimester human embryos and young adults was characterized using mass spectrometry and analyzed for changes in protein levels that may relate to structural changes occurring during this time. This vitreous proteome was compared to previous reports to confirm proteins already identified and reveal novel ones. METHODS. Vitreous from 17 human embryos aged 14 to 20 weeks gestation (WG) and from a 12-, a 14-, a 15-, and a 28-year-old was individually analyzed using tandem mass spectrometry-based proteomics. Peptide spectral count associations with embryonic age were assessed using a general linear model of fold changes and Spearman's rank correlation. Differences between embryonic and young adult vitreous proteomes were also compared. Immunohistochemistry was used to evaluate three proteins in five additional fetal (10-18 WG) human eyes. RESULTS. There were 1217 proteins identified in fetal and young adult human vitreous, 206 after quantile normalization and variance filtering. In embryos, the peptide counts of 37 proteins changed significantly from 14 to 20 WG: 75.7% increased, 24.3% decreased. Immunohistochemistry confirmed the absence of clusterin and cadherin in 10 and 14 WG eyes and their presence at 18 WG. Comparing embryonic to young adult vitreous, 47 proteins were significantly higher or lower. A total of 768 proteins not previously identified in the literature are presented. CONCLUSIONS. Proteins previously unreported in the human vitreous were identified. The human vitreous proteome undergoes significant changes during embryogenesis and young adulthood. A number of protein levels change considerably during the second trimester, with the majority decreasing. C1 [Yee, Kenneth M. P.; Sebag, J.] VMR Inst Vitreous Macula Retina, Huntington Beach, CA 92647 USA. [Yee, Kenneth M. P.; Ross-Cisneros, Fred N.; Sadun, Alfredo A.; Sebag, J.] Doheny Eye Inst, Los Angeles, CA 90033 USA. [Feener, Edward P.; Gao, Ben-Bo; Aiello, Lloyd Paul] Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. [Madigan, Michele] Univ New S Wales, Sch Optometry & Vis Sci, Sydney, NSW, Australia. [Madigan, Michele] Univ Sydney, Save Sight Inst, Sydney, NSW 2006, Australia. [Jackson, Nicholas J.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med Stat Core, Los Angeles, CA 90095 USA. [Provis, Jan] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2601, Australia. [Provis, Jan] Australian Natl Univ, Canberra, ACT, Australia. [Aiello, Lloyd Paul] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Sadun, Alfredo A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA. RP Sebag, J (reprint author), VMR Inst Vitreous Macula Retina, 7677 Ctr Ave,Suite 400, Huntington Beach, CA 92647 USA. EM jsebag@VMRinstitute.com OI Sebag, J/0000-0001-8648-5747 FU NIDDK NIH HHS [P30 DK036836] NR 45 TC 2 Z9 2 U1 1 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 2015 VL 56 IS 12 BP 7036 EP 7042 DI 10.1167/iovs.15-16809 PG 7 WC Ophthalmology SC Ophthalmology GA DB0ZS UT WOS:000368238200005 PM 26529037 ER PT J AU Kheirkhah, A Darabad, RR Cruzat, A Hajrasouliha, AR Witkin, D Wong, N Dana, R Hamrah, P AF Kheirkhah, Ahmad Darabad, Raheleh Rahimi Cruzat, Andrea Hajrasouliha, Amir Reza Witkin, Deborah Wong, Nadia Dana, Reza Hamrah, Pedram TI Corneal Epithelial Immune Dendritic Cell Alterations in Subtypes of Dry Eye Disease: A Pilot In Vivo Confocal Microscopic Study SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE dry eye disease; in vivo confocal microscopy; inflammation; dendritic cells ID ANTIGEN-PRESENTING CELLS; OCULAR-SURFACE; SJOGRENS-SYNDROME; NERVE MORPHOLOGY; KERATITIS; DENSITY; CLASSIFICATION AB PURPOSE. To evaluate density and morphology of corneal epithelial immune dendritic cells (DCs) in different subtypes of dry eye disease (DED) using in vivo confocal microscopy (IVCM). METHODS. This retrospective study included 59 eyes of 37 patients with DED and 40 eyes of 20 age-matched healthy controls. Based on clinical tests, eyes with DED were categorized into two subtypes: aqueous-deficient (n = 35) and evaporative (n = 24). For all subjects, images of laser scanning in vivo confocal microscopy (IVCM) of the central cornea were analyzed for DC density and DC morphology (DC size, number of dendrites, and DC field). These DC parameters were compared among all dry eye and control groups. RESULTS. Compared with the controls, patients with DED had significantly higher DC density, larger DC size, higher number of dendrites, and larger DC field (all P < 0.001). Comparison between aqueous-deficient and evaporative subtypes demonstrated that DC density was significantly higher in aqueous-deficient subtype (189.8 +/- 36.9 vs. 58.9 +/- 9.4 cells/mm(2), P = 0.001). However, there were no significant differences in morphologic parameters between DED subtypes. When aqueous-deficient DED with underlying systemic immune disease (Sjogren's syndrome and graft versus host disease) were compared with nonimmune conditions, the immunologic subgroup showed significantly higher DC density, DC size, and number of dendrites (all P < 0.05). CONCLUSIONS. Corneal IVCM demonstrated differential changes in DC density and morphologic DC parameters between subtypes of DED. These changes, which reflect the degree of immune activation and inflammation in DED, can be used for clinical practice and endpoints in clinical trials. C1 [Kheirkhah, Ahmad; Darabad, Raheleh Rahimi; Cruzat, Andrea; Hajrasouliha, Amir Reza; Witkin, Deborah; Wong, Nadia; Hamrah, Pedram] Harvard Univ, Sch Med, Ocular Surface Imaging Ctr, Boston, MA USA. [Cruzat, Andrea] Pontificia Univ Chile, Dept Ophthalmol, Santiago, Chile. [Cruzat, Andrea] Harvard Univ, Sch Med, Dept Ophthalmol, Cornea Serv,Massachusetts Eye & Ear Infirm, Boston, MA USA. [Dana, Reza; Hamrah, Pedram] Tufts Univ, Boston Image Reading Ctr, Sch Med, Boston, MA 02111 USA. [Hamrah, Pedram] Tufts Univ, Cornea Serv, Sch Med, New England Eye Ctr,Tufts Med Ctr,Dept Ophthalmol, Boston, MA 02111 USA. RP Hamrah, P (reprint author), Tufts Univ, Boston Image Reading Ctr, Sch Med, 800 Washington St, Boston, MA 02111 USA. EM phamrah@tuftsmedicalcenter.org FU NEI NIH HHS [K08 EY020575, K08-EY020575] NR 41 TC 6 Z9 6 U1 2 U2 6 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 2015 VL 56 IS 12 BP 7179 EP 7185 DI 10.1167/iovs.15-17433 PG 7 WC Ophthalmology SC Ophthalmology GA DB0ZS UT WOS:000368238200023 PM 26540656 ER PT J AU Adler, JT Yeh, H AF Adler, Joel T. Yeh, Heidi TI Identification of Race and Ethnicity in Large Databases SO JAMA SURGERY LA English DT Letter ID DIALYSIS C1 [Adler, Joel T.; Yeh, Heidi] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Adler, JT (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,GRB 425, Boston, MA 02114 USA. EM jtadler@mgh.harvard.edu OI Adler, Joel/0000-0001-8190-3444 NR 4 TC 0 Z9 0 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6254 EI 2168-6262 J9 JAMA SURG JI JAMA Surg. PD NOV PY 2015 VL 150 IS 11 BP 1099 EP 1099 DI 10.1001/jamasurg.2015.2228 PG 1 WC Surgery SC Surgery GA DA7MA UT WOS:000367987100025 PM 26287810 ER PT J AU Peacock, ZS Tricomi, BJ Faquin, WC Magill, JC Murphy, BA Kaban, LB Troulis, MJ AF Peacock, Zachary S. Tricomi, Brad J. Faquin, William C. Magill, John C. Murphy, Brian A. Kaban, Leonard B. Troulis, Maria J. TI Bilateral Continuous Automated Distraction Osteogenesis: Proof of Principle SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Article DE Automated continuous distraction osteogenesis; distraction wound; mandibular distraction osteogenesis; regenerate ID BONE DISTRACTION; HISTOMORPHOMETRIC ANALYSIS; MANDIBULAR DEFORMITIES; CLINICAL-APPLICATION; DEVICE; FREQUENCY; MINIPIGS; TISSUES; REGENERATION; MYOCYTES AB The purpose of this study was to demonstrate that automated, continuous, curvilinear distraction osteogenesis (DO) in a minipig model is effective when performed bilaterally, at rates up to 3mm/day, to achieve clinically relevant lengthening.A Yucatan minipig in the mixed dentition phase underwent bilaterally, at a continuous DO at a rate of 2mm/day at the center of rotation; 1.0 and 3.0mm/day at the superior and inferior regions, respectively. The distraction period was 13 days with no latency period. Vector and rate of distraction were remotely monitored without radiographs, using the device sensor. After fixation and euthanasia, the mandible and digastric muscles were harvested. The ex vivo appearance, stability, and radiodensity of the regenerate were evaluated using a semiquantitative scale. Percent surface area (PSA) occupied by bone, fibrous tissue, cartilage, and hematoma were calculated using histomorphometrics. The effects of DO on the digastric muscles and mandibular condyles were assessed via microscopy, and degenerative changes were quantified.The animal was distracted to 21mm and 24mm on the right and left sides, respectively. Clinical appearance, stability, and radiodensity were scored as 3 bilaterally indicating osseous union. The total PSA occupied by bone (right=75.532.19%; left PSA=73.11 +/- 2.18%) approached that of an unoperated mandible (84.67 +/- 0.86%). Digastric muscles and condyles showed negligible degenerative or abnormal histologic changes.This proof of principle study is the first report of osseous healing with no ill-effect on associated soft tissue and the mandibular condyle using bilateral, automated, continuous, and curvilinear DO at rates up to 3mm/day. The model approximates potential human application of continuous automated distraction with a semiburied device. C1 [Peacock, Zachary S.; Kaban, Leonard B.] Dept Oral & Maxillofacial Surg, Boston, MA USA. [Tricomi, Brad J.] Univ Massachusetts, Boston, MA 02125 USA. [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Magill, John C.; Murphy, Brian A.] Phys Sci Inc, Andover, MA 01810 USA. [Troulis, Maria J.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Peacock, ZS (reprint author), Massachusetts Gen Hosp, Warren Bldg 1201,55 Fruit St, Boston, MA 02114 USA. EM zpeacock@partners.org FU NIH/NIDCR SBIR grant [5R44DE019047-03]; Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund; Hanson Foundation (Boston, MA) FX This work was funded by NIH/NIDCR SBIR grant (5R44DE019047-03), the Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund, and the Hanson Foundation (Boston, MA). NR 36 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1049-2275 EI 1536-3732 J9 J CRANIOFAC SURG JI J. Craniofac. Surg. PD NOV PY 2015 VL 26 IS 8 BP 2320 EP 2324 DI 10.1097/SCS.0000000000001996 PG 5 WC Surgery SC Surgery GA DA7XC UT WOS:000368017700021 PM 26594967 ER PT J AU Tse, JY Adisa, M Goldberg, LJ Nazarian, RM AF Tse, Julie Y. Adisa, Morayo Goldberg, Lynne J. Nazarian, Rosalynn M. TI Dermatopathologic manifestations of intravenous drug use SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article DE heroin; intravenous drug use; necrobiosis lipoidica; pigment deposition; vasculitis ID CUTANEOUS MANIFESTATIONS; NECROBIOSIS LIPOIDICA; NECROTIZING ANGIITIS; SKIN-LESIONS; ABUSE; INJECTIONS; VASCULITIS; COMPLICATIONS; ADDICTION; DIAGNOSIS AB Background The rate of intravenous drug use (IVDU) has been increasing nationally; however, cutaneous manifestations of IVDU have infrequently been investigated. We report a series of the clinicopathological correlation of IVDU in the skin. Methods A search of surgical pathology files between the years 2000 and 2014 was performed for cutaneous specimens from patients with a reported history of IVDU for which the histopathological findings could not be attributed to another etiology. Ten cases for which slides were available were included in the study. Results Patients had an average age of 39.7 years and had active or recent history of IVDU. Clinical impressions included ulcer, granulomatous dermatitis, vasculitis, pyoderma gangrenosum and hyperpigmentation at injection sites. Histopathology revealed leukocytoclastic vasculitis (n = 2), dermal pigment deposition (n = 3), non-specific ulceration/scarring (n = 4) and necrobiosis lipoidica-like dermatitis (n = 1). No infectious etiology or polarizable foreign material was identified in any case. Conclusions Cutaneous manifestations of IVDU should be considered in the differential as an etiology for dermatopathologic findings in high-risk patients. We report histopathological findings beyond the scope of those most commonly associated with IVDU. We aim to raise awareness of the cutaneous manifestations of IVDU to improve clinicopathological correlation and patient management in light of the ongoing epidemic. C1 [Tse, Julie Y.; Adisa, Morayo; Nazarian, Rosalynn M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Tse, Julie Y.; Adisa, Morayo; Nazarian, Rosalynn M.] Harvard Univ, Sch Med, Boston, MA USA. [Goldberg, Lynne J.] Boston Med Ctr, Dept Dermatol, Boston, MA USA. [Goldberg, Lynne J.] Boston Med Ctr, Dept Pathol & Lab Med, Boston, MA USA. RP Nazarian, RM (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 829A, Boston, MA 02114 USA. EM rmnazarian@partners.org NR 26 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0303-6987 EI 1600-0560 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD NOV PY 2015 VL 42 IS 11 BP 815 EP 823 DI 10.1111/cup.12622 PG 9 WC Dermatology; Pathology SC Dermatology; Pathology GA DB1UA UT WOS:000368293300004 PM 26345172 ER PT J AU Gaudin, R AF Gaudin, Raphal TI Enhancing our single molecule experience using CRISPR SO M S-MEDECINE SCIENCES LA French DT News Item ID CLATHRIN-COATED PIT C1 [Gaudin, Raphal] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Gaudin, Raphal] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. RP Gaudin, R (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, WAB 136,200 Longwood Ave, Boston, MA 02115 USA. EM raphael.gaudin@childrens.harvard.edu NR 9 TC 3 Z9 3 U1 2 U2 2 PU EDP SCIENCES S A PI LES ULIS CEDEX A PA 17, AVE DU HOGGAR, PA COURTABOEUF, BP 112, F-91944 LES ULIS CEDEX A, FRANCE SN 0767-0974 J9 M S-MED SCI JI M S-Med. Sci. PD NOV PY 2015 VL 31 IS 11 BP 959 EP 961 DI 10.1051/medsci/20153111007 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DB1FT UT WOS:000368254200007 PM 26576600 ER PT J AU Carley, JA Karp, JF Gentili, A Marcum, ZA Reid, MC Rodriguez, E Rossi, MI Shega, J Thielke, S Weiner, DK AF Carley, Joseph A. Karp, Jordan F. Gentili, Angela Marcum, Zachary A. Reid, M. Carrington Rodriguez, Eric Rossi, Michelle I. Shega, Joseph Thielke, Stephen Weiner, Debra K. TI Deconstructing Chronic Low Back Pain in the Older Adult: Step by Step Evidence and Expert-Based Recommendations for Evaluation and Treatment SO PAIN MEDICINE LA English DT Article DE Aged; Assessment; Depression; Chronic Pain; Elderly; Low Back Pain; Primary Care ID COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; MAJOR DEPRESSIVE DISORDER; PRIMARY-CARE PATIENTS; STAR-ASTERISK-D; LATE-LIFE; PSYCHOSOCIAL INTERVENTIONS; MEDICATION USE; HEALTH-CARE; OUTCOMES AB Objective. To present the fourth in a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults. The series presents CLBP as a syndrome, a final common pathway for the expression of multiple contributors rather than a disease localized exclusively to the lumbosacral spine. Each article addresses one of twelve important contributors to pain and disability in older adults with CLBP. This article focuses on depression. Methods. The evaluation and treatment algorithm, a table articulating the rationale for the individual algorithm components, and stepped-care drug recommendations were developed using a modified Delphi approach. The Principal Investigator, a three-member content expert panel, and a nine-member primary care panel were involved in the iterative development of these materials. The algorithm was developed keeping in mind medications and other resources available within Veterans Health Administration (VHA) facilities. As panelists were not exclusive to the VHA, the materials can be applied in both VHA and civilian settings. The illustrative clinical case was taken from one of the contributor's clinical practice. Results. We present an algorithm and supportive materials to help guide the care of older adults with depression, an important contributor to CLBP. The case illustrates an example of a complex clinical presentation in which depression was an important contributor to symptoms and disability in an older adult with CLBP. Conclusions. Depression is common and should be evaluated routinely in the older adult with CLBP so that appropriately targeted treatments can be planned and implemented. C1 [Carley, Joseph A.; Karp, Jordan F.; Weiner, Debra K.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Karp, Jordan F.; Weiner, Debra K.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA USA. [Karp, Jordan F.; Weiner, Debra K.] Univ Pittsburgh, Clin & Translat Sci Inst, Pittsburgh, PA USA. [Gentili, Angela] Hunter Holmes McGuire VA Med Ctr, Richmond, VA USA. [Gentili, Angela] Virginia Commonwealth Univ Hlth Syst, Richmond, VA USA. [Marcum, Zachary A.] Univ Washington, Sch Pharm, Seattle, WA 98195 USA. [Reid, M. Carrington] Weill Cornell Med Coll, Div Geriatr & Palliat Med, New York, NY USA. [Rodriguez, Eric] Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA USA. [Rossi, Michelle I.] VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA USA. [Shega, Joseph] VITAS Healthcare, Miami, FL USA. [Thielke, Stephen] Puget Sound VA Med Ctr, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Thielke, Stephen] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Rossi, Michelle I.; Weiner, Debra K.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Rossi, Michelle I.; Weiner, Debra K.] Univ Pittsburgh, Dept Med, Div Geriatr Med, Pittsburgh, PA USA. RP Karp, JF (reprint author), Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA. EM karpjf@upmc.edu FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development Service; ADAPT Project: Addressing Depression and Pain Together [AG033575] FX This material is based on work supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development Service. Dr. Karp would like to acknowledge grant AG033575 (the ADAPT Project: Addressing Depression and Pain Together), which provided support for his work on this article. The contents of this report do not represent the views of the Department of Veterans Affairs or the US government. The authors thank Dave Newman for his thoughtful review of the manuscript. NR 68 TC 3 Z9 3 U1 3 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1526-2375 EI 1526-4637 J9 PAIN MED JI Pain Med. PD NOV PY 2015 VL 16 IS 11 BP 2098 EP 2108 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA DB1VH UT WOS:000368296600007 PM 26539754 ER PT J AU Yamada, Y Rex, NS Hotta, K Ohura, T Boskovic, S Madsen, J Colvin, R Benichou, G Cosimi, B Kawai, T AF Yamada, Yohei Rex, Neal Smith Hotta, Kiyohiko Ohura, Tetsu Boskovic, Svjetlan Madsen, Joren Colvin, Robert Benichou, Gilles Cosimi, Ben Kawai, Tatsuo TI CONTINUOUS IL-2 EXPOSURE BREAKS RENAL ALLOGRAFT TOLERANCE INDUCED VIA MIXED CHIMERISM PROTOCOL IN NONHUMAN PRIMATES SO TRANSPLANT INTERNATIONAL LA English DT Meeting Abstract C1 [Yamada, Yohei] Keio Univ, Sch Med, Dept Pediat Surg, Tokyo 108, Japan. [Rex, Neal Smith; Colvin, Robert] Massachusetts Gen Hosp, Pathol, Boston, MA 02114 USA. [Hotta, Kiyohiko; Ohura, Tetsu; Boskovic, Svjetlan; Madsen, Joren; Benichou, Gilles; Cosimi, Ben; Kawai, Tatsuo] Massachusetts Gen Hosp, Tranplant Surg, Boston, MA 02114 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 0934-0874 EI 1432-2277 J9 TRANSPL INT JI Transpl. Int. PD NOV PY 2015 VL 28 SU 4 SI SI MA O341 BP 124 EP 124 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA DA3VE UT WOS:000367726700337 ER PT J AU Harvey, LD Yin, Y Attarwala, IY Begum, G Deng, J Yan, HQ Dixon, CE Sun, DD AF Harvey, Lloyd D. Yin, Yan Attarwala, Insiya Y. Begum, Gulnaz Deng, Julia Yan, Hong Q. Dixon, C. Edward Sun, Dandan TI Administration of DHA Reduces Endoplasmic Reticulum Stress-Associated Inflammation and Alters Microglial or Macrophage Activation in Traumatic Brain Injury SO ASN NEURO LA English DT Article DE cortical contusion injury; docosahexaenoic acid; microglial polarization; neuroinflammation; nuclear factor kappa-light-chain-enhancer of activated B cells; secondary injury ID MICROGLIA/MACROPHAGE POLARIZATION DYNAMICS; DOCOSAHEXAENOIC ACID; OXIDATIVE STRESS; FATTY-ACID; ER STRESS; RESPONSES; IMPACT; RAT; EXPRESSION; DISEASES AB We investigated the effects of the administration of docosahexaenoic acid (DHA) post-traumatic brain injury (TBI) on reducing neuroinflammation. TBI was induced by cortical contusion injury in Sprague Dawley rats. Either DHA (16mg/kg in dimethyl sulfoxide) or vehicle dimethyl sulfoxide (1ml/kg) was administered intraperitonially at 5min after TBI, followed by a daily dose for 3 to 21 days. TBI triggered activation of microglia or macrophages, detected by an increase of Iba1 positively stained microglia or macrophages in peri-lesion cortical tissues at 3, 7, and 21 days post-TBI. The inflammatory response was further characterized by expression of the proinflammatory marker CD16/32 and the anti-inflammatory marker CD206 in Iba1(+) microglia or macrophages. DHA-treated brains showed significantly fewer CD16/32(+) microglia or macrophages, but an increased CD206(+) phagocytic microglial or macrophage population. Additionally, DHA treatment revealed a shift in microglial or macrophage morphology from the activated, amoeboid-like state into the more permissive, surveillant state. Furthermore, activated Iba1(+) microglial or macrophages were associated with neurons expressing the endoplasmic reticulum (ER) stress marker CHOP at 3 days post-TBI, and the administration of DHA post-TBI concurrently reduced ER stress and the associated activation of Iba1(+) microglial or macrophages. There was a decrease in nuclear translocation of activated nuclear factor kappa-light-chain-enhancer of activated B cells protein at 3 days in DHA-treated tissue and reduced neuronal degeneration in DHA-treated brains at 3, 7, and 21 days after TBI. In summary, our study demonstrated that TBI mediated inflammatory responses are associated with increased neuronal ER stress and subsequent activation of microglia or macrophages. DHA administration reduced neuronal ER stress and subsequent association with microglial or macrophage polarization after TBI, demonstrating its therapeutic potential to ameliorate TBI-induced cellular pathology. C1 [Harvey, Lloyd D.; Attarwala, Insiya Y.; Begum, Gulnaz; Deng, Julia; Sun, Dandan] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. [Yin, Yan] Dalian Med Univ, Hosp 2, Dept Neurol, Dalian, Peoples R China. [Yan, Hong Q.; Dixon, C. Edward] Univ Pittsburgh, Brain Trauma Res Ctr, Dept Neurosurg, Pittsburgh, PA 15213 USA. [Yan, Hong Q.; Dixon, C. Edward; Sun, Dandan] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Sun, DD (reprint author), Univ Pittsburgh, Med Ctr, Dept Neurol, S-598 South Biomed Sci Tower,3500 Terrace St, Pittsburgh, PA 15213 USA. EM sund@upmc.edu OI Harvey, Lloyd/0000-0001-5934-9934; Yin, Yan/0000-0002-5982-7462 FU University of Pittsburgh Neurology Departmental start-up funds; UPMC Endowed Chair Professorship on Brain Disorder Research; National Institutes of Health [R01NS089051]; United States Department of Veterans Aairs VA [RRD#B6761R]; Brackenridge Summer and Fall Research Fellowships; Chancellor's Undergraduate Research Fellowship; Honors College-Health Sciences Research Fellowship; James V. Kunkel, M.D. Translational Research Fellowship; Chinese Dalian Municipal Bureau Study Abroad Research Award FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported in part by University of Pittsburgh Neurology Departmental start-up funds, a UPMC Endowed Chair Professorship on Brain Disorder Research, and the National Institutes of Health [R01NS089051] (DS) and the United States Department of Veterans Aairs VA [RR&D#B6761R] (CED). LDH was supported by the Brackenridge Summer and Fall Research Fellowships, the Chancellor's Undergraduate Research Fellowship, the Honors College-Health Sciences Research Fellowship, and the James V. Kunkel, M.D. Translational Research Fellowship. YY was supported by the Chinese Dalian Municipal Bureau Study Abroad Research Award. NR 37 TC 6 Z9 6 U1 1 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1759-0914 J9 ASN NEURO JI ASN Neuro PD NOV-DEC PY 2015 VL 7 IS 6 DI 10.1177/1759091415618969 PG 15 WC Neurosciences SC Neurosciences & Neurology GA DA2EH UT WOS:000367607600003 ER PT J AU Dhar, M Wong, J Karimi, A Che, J Renier, C Matsumoto, M Triboulet, M Garon, EB Goldman, JW Rettig, MB Jeffrey, SS Kulkarni, RP Sollier, E Di Carlo, D AF Dhar, Manjima Wong, Jessica Karimi, Armin Che, James Renier, Corinne Matsumoto, Melissa Triboulet, Melanie Garon, Edward B. Goldman, Jonathan W. Rettig, Matthew B. Jeffrey, Stefanie S. Kulkarni, Rajan P. Sollier, Elodie Di Carlo, Dino TI High efficiency vortex trapping of circulating tumor cells SO BIOMICROFLUIDICS LA English DT Article ID METASTATIC BREAST-CANCER; HETEROGENEITY; SIZE; SEPARATION; CAPTURE; SYSTEM; CHIP AB Circulating tumor cells (CTCs) are important biomarkers for monitoring tumor dynamics and efficacy of cancer therapy. Several technologies have been demonstrated to isolate CTCs with high efficiency but achieve a low purity from a large background of blood cells. We have previously shown the ability to enrich CTCs with high purity from large volumes of blood through selective capture in microvortices using the Vortex Chip. The device consists of a narrow channel followed by a series of expansion regions called reservoirs. Fast flow in the narrow entry channel gives rise to inertial forces, which direct larger cells into trapping vortices in the reservoirs where they remain circulating in orbits. By studying the entry and stability of particles following entry into reservoirs, we discover that channel cross sectional area plays an important role in controlling the size of trapped particles, not just the orbital trajectories. Using these design modifications, we demonstrate a new device that is able to capture a wider size range of CTCs from clinical samples, uncovering further heterogeneity. This simple biophysical method opens doors for a range of downstream interventions, including genetic analysis, cell culture, and ultimately personalized cancer therapy. (C) 2015 AIP Publishing LLC. C1 [Dhar, Manjima; Wong, Jessica; Karimi, Armin; Che, James; Matsumoto, Melissa; Di Carlo, Dino] Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA 90095 USA. [Dhar, Manjima; Karimi, Armin; Che, James; Di Carlo, Dino] Calif NanoSyst Inst, Los Angeles, CA 90095 USA. [Renier, Corinne; Sollier, Elodie] Vortex Biosci Inc, Menlo Labs, Menlo Pk, CA 94025 USA. [Triboulet, Melanie; Jeffrey, Stefanie S.] Stanford Univ, Sch Med, Dept Surg, Stanford, CA 94305 USA. [Garon, Edward B.; Goldman, Jonathan W.] Univ Calif Los Angeles, Med Ctr, Div Hematol Oncol, Los Angeles, CA 90095 USA. [Rettig, Matthew B.] Univ Calif Los Angeles, Med Ctr, Dept Urol, Los Angeles, CA 90095 USA. [Rettig, Matthew B.] VA Greater Los Angeles Healthcare Syst, Div Hematol Oncol, Los Angeles, CA 90073 USA. [Kulkarni, Rajan P.] Univ Calif Los Angeles, Med Ctr, Div Dermatol, Los Angeles, CA 90095 USA. RP Sollier, E (reprint author), Vortex Biosci Inc, Menlo Labs, 1455 Adams Dr,Suite 2010, Menlo Pk, CA 94025 USA. EM elodie@vortexbiosciences.com; dicarlo@ucla.edu FU Vortex Biosciences, Inc.; Office of Naval Research Young Investigator Program [N000141210847] FX The authors thank Dr. Oladunni Adeyiga, clinical coordinators, nurses, and all donors for their contributions toward blood sample collection. We thank Edward Pao for the PSA staining and Clementine Lemaire for the Vimentin/N-Cadherin staining optimization. This work was funded by Vortex Biosciences, Inc., and Office of Naval Research Young Investigator Program (Grant No. N000141210847). We would like to disclose the following conflicts of interest: The University of California, Los Angeles, D. Di Carlo, E. Sollier, and C. Renier have financial interests in Vortex Biosciences. NR 33 TC 4 Z9 5 U1 4 U2 10 PU AMER INST PHYSICS PI MELVILLE PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA SN 1932-1058 J9 BIOMICROFLUIDICS JI Biomicrofluidics PD NOV PY 2015 VL 9 IS 6 AR 064116 DI 10.1063/1.4937895 PG 12 WC Biochemical Research Methods; Biophysics; Nanoscience & Nanotechnology; Physics, Fluids & Plasmas SC Biochemistry & Molecular Biology; Biophysics; Science & Technology - Other Topics; Physics GA DA5CZ UT WOS:000367821100020 PM 26697126 ER PT J AU Arias, SA Sullivan, AF Miller, I Camargo, CA Boudreaux, ED AF Arias, Sarah A. Sullivan, Ashley F. Miller, Ivan Camargo, Carlos A., Jr. Boudreaux, Edwin D. TI Implementation and use of a crisis hotline during the treatment as usual and universal screening phases of a suicide intervention study SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Crisis hotlines; Suicide risk; Research safety protocol; Public health ID CALLERS AB Background: Although research suggests that crisis hotlines are an effective means of mitigating suicide risk, lack of empirical evidence may limit the use of this method as a research safety protocol. Purpose: This study describes the use of a crisis hotline to provide clinical backup for research assessments. Methods: Data were analyzed from participants in the Emergency Department Safety and Follow-up Evaluation (ED-SAFE) study (n = 874). Socio-demographics, call completion data, and data available on suicide attempts occurring in relation to the crisis counseling call were analyzed. Pearson chi-squared statistic for differences in proportions were conducted to compare characteristics of patients receiving versus not receiving crisis counseling. P <0.05 was considered statistically significant. Results: Overall, there were 163 counseling calls (6% of total assessment calls) from 135 (16%) of the enrolled subjects who were transferred to the crisis line because of suicide risk identified during the research assessment. For those transferred to the crisis line, the median age was 40 years (interquartile range 27-48) with 67% female, 80% white, and 11% Hispanic. Conclusions: Increasing demand for suicide interventions in diverse healthcare settings warrants consideration of crisis hotlines as a safety protocol mechanism. Our findings provide background on how a crisis hotline was implemented as a safety measure, as well as the type of patients who may utilize this safety protocol. (C) 2015 Elsevier Inc. All rights reserved. C1 [Arias, Sarah A.; Miller, Ivan] Butler Hosp, Providence, RI 02906 USA. [Arias, Sarah A.; Miller, Ivan] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Sullivan, Ashley F.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Emergency Med, Worcester, MA USA. [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA. RP Arias, SA (reprint author), Butler Hosp, Dept Psychiat & Human Behav, 345 Blackstone Blvd, Providence, RI 02906 USA. EM sarias@butler.org OI Arias, Sarah/0000-0003-1832-8824 FU National Institute on Mental Health [U01MH088278] FX The project described was supported by Award Number U01MH088278 from the National Institute on Mental Health. 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. None of the authors have financial conflicts of interest to disclose. NR 9 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 EI 1559-2030 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD NOV PY 2015 VL 45 BP 147 EP 150 DI 10.1016/j.cct.2015.08.015 PN B PG 4 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA DA4FJ UT WOS:000367755200001 PM 26341724 ER PT J AU Pigeon, WR Heffner, KL Crean, H Gallegos, AM Walsh, P Seehuus, M Cerulli, C AF Pigeon, Wilfred R. Heffner, Kathi L. Crean, Hugh Gallegos, Autumn M. Walsh, Patrick Seehuus, Martin Cerulli, Catherine TI Responding to the need for sleep among survivors of interpersonal violence: A randomized controlled trial of a cognitive-behavioral insomnia intervention followed by PTSD treatment SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Sleep; Insomnia; Posttraumatic stress disorder; Depression; Interpersonal violence; Cognitive-behavioral therapy; Community-based participatory research ID POSTTRAUMATIC-STRESS-DISORDER; INTIMATE PARTNER VIOLENCE; MAJOR DEPRESSIVE DISORDER; MISSING DATA; PRIMARY-CARE; PSYCHIATRIC-DISORDERS; PHYSICAL HEALTH; SEXUAL ASSAULT; THERAPY; CLINICIAN AB Sleep disturbance is a common feature of posttraumatic stress disorder (PTSD), but is not a focus of standard PTSD treatments. Psychological trauma exposure is associated with considerable physical and mental health morbidity, possibly due to the alterations in neuroendocrine function and inflammation observed in trauma exposed individuals. Although PTSD treatments are efficacious, they are associated with high drop-out rates in clinical trials and clinical practice. Finally, individuals with PTSD stemming from exposure to interpersonal violence represent an especially under-treated population with significant sleep disturbance. Community-based participatory research was utilized to design and prepare a clinical trial that randomizes recent survivors of interpersonal violence who have PTSD, depression, and insomnia to receive either: (1) Cognitive Behavioral Therapy for Insomnia (CBTi) followed by Cognitive Processing Therapy (CPT) for trauma, or (2) attention control followed by CPT. Outcome measures include subjective and objective measures of sleep, clinician-administered PTSD and depression scales, inflammatory cytokines, and salivary cortisol. Assessments are conducted at baseline, following the sleep or control intervention, and again following CPT. The design allows for: (1) the first test of a sleep intervention in this population; (2) the comparison of sequenced CBTi and CPT to attention control followed by CPT, and (3) assessing the roles of neuroendocrine function, inflammatory processes, and objective sleep markers in mediating treatment outcomes. The study's overarching hypothesis is that treating insomnia will produce reduction in insomnia, PTSD, and depression severity, allowing patients to more fully engage in, and derive optimal benefits from, cognitive processing therapy. Published by Elsevier Inc. C1 [Pigeon, Wilfred R.; Heffner, Kathi L.; Gallegos, Autumn M.; Walsh, Patrick; Seehuus, Martin] Univ Rochester, Sleep & Neurophysiol Res Lab, Med Ctr, Dept Psychiat, Rochester, NY 14642 USA. [Pigeon, Wilfred R.] US Dept Vet Affairs, Ctr Excellence Suicide Prevent, Canandaigua VA Med Ctr, Canandaigua, NY USA. [Crean, Hugh] Univ Rochester, Sch Nursing, Med Ctr, Rochester, NY 14642 USA. [Cerulli, Catherine] Univ Rochester, Susan B Anthony Ctr, Med Ctr, Rochester, NY 14642 USA. [Cerulli, Catherine] Univ Rochester, Lab Interpersonal Violence & Victimizat, Med Ctr, Rochester, NY 14642 USA. RP Pigeon, WR (reprint author), Univ Rochester, Sleep & Neurophysiol Res Lab, Med Ctr, 300 Crittenden Blvd Box PSYCH, Rochester, NY 14642 USA. EM Wilfred_pigeon@urmc.rochester.edu OI Heffner, Kathi/0000-0003-1095-1873; Crean, Hugh/0000-0001-7292-7700 FU National Institute of Nursing Research at the National Institute of Health [R01NR013909] FX The work presented here was funded by the National Institute of Nursing Research at the National Institute of Health (R01NR013909). The trial is registered with clinical trilas.gov (NCT01743339). NR 70 TC 0 Z9 0 U1 7 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 EI 1559-2030 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD NOV PY 2015 VL 45 BP 252 EP 260 DI 10.1016/j.cct.2015.08.019 PN B PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA DA4FJ UT WOS:000367755200017 PM 26343743 ER PT J AU Moy, ML Wayne, PM Litrownik, D Beach, D Klings, ES Davis, RB Yeh, GY AF Moy, Marilyn L. Wayne, Peter M. Litrownik, Daniel Beach, Douglas Klings, Elizabeth S. Davis, Roger B. Yeh, Gloria Y. TI Long-term Exercise After Pulmonary Rehabilitation (LEAP): Design and rationale of a randomized controlled trial of Tai Chi SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Pulmonary rehabilitation; Exercise; Physical activity; Mind-body therapies; Chronic obstructive pulmonary disease ID CHRONIC HEART-FAILURE; QUALITY-OF-LIFE; RESPIRATORY SOCIETY STATEMENT; OBSTRUCTIVE LUNG-DISEASE; ALL-CAUSE MORTALITY; DAILY STEP COUNTS; PHYSICAL-ACTIVITY; CARDIORESPIRATORY FUNCTION; UNITED-STATES; CHUAN PRACTITIONERS AB Background: Persons with chronic obstructive pulmonary disease (COPD) have reduced exercise capacity and levels of physical activity. Supervised, facility-based pulmonary rehabilitation programs improve exercise capacity and reduce dyspnea, but novel long-term strategies are needed to maintain the benefits gained. Mind-body modalities such as Tai Chi which combine aerobic activity, coordination of breathing, and cognitive techniques that alleviate the physical inactivity, dyspnea, and anxiety and depression that are the hallmarks of COPD are promising strategies. Methods/Design: We have designed a randomized controlled study to examine whether Tai Chi will maintain exercise capacity in persons with COPD who have recently completed a supervised pulmonary rehabilitation program, compared to standard care. The primary outcome is 6-min walk test distance at 6 months. Secondary outcomes include health-related quality of life, dyspnea, mood, occurrence of acute exacerbations, engagement in physical activity, exercise self-efficacy, and exercise adherence. Simultaneously, we are conducting a pilot study of group walking. We will enroll 90 persons who will be randomized to one of three arms in a 2:2:1 ratio: Tai Chi, standard care, or group-based walking. Discussion: The Long-term Exercise After Pulmonary Rehabilitation (LEAP) study is a novel and clinically relevant trial. We will enroll a well-characterized cohort of persons with COPD and will comprehensively assess physiological and psychosocial outcomes. Results of this study will provide the evidence base for persons with COPD to engage in Tai Chi as a low-cost, long-term modality to sustain physical activity in persons who have completed a standard short-term pulmonary rehabilitation program. Published by Elsevier Inc. C1 [Moy, Marilyn L.] Vet Adm Boston Healthcare Syst, Dept Med, Pulm & Crit Care Med Sect, Boston, MA USA. [Wayne, Peter M.] Brigham & Womens Hosp, Osher Ctr Integrat Med, Boston, MA 02115 USA. [Wayne, Peter M.] Harvard Univ, Sch Med, Boston, MA USA. [Wayne, Peter M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. [Litrownik, Daniel; Davis, Roger B.; Yeh, Gloria Y.] Beth Israel Deaconess Med Ctr, Dept Med, Div Gen Med & Primary Care, Brookline, MA USA. [Beach, Douglas] Beth Israel Deaconess Med Ctr, Dept Med, Div Pulm Sleep & Crit Care Med, Boston, MA 02215 USA. [Klings, Elizabeth S.] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. RP Moy, ML (reprint author), Pulm & Crit Care Sect, VA Boston Healthcare Syst, 1400 VFW Pkwy,Mail Code 111PI, West Roxbury, MA 02132 USA. EM marilyn.moy@va.gov; pwayne@partners.org; dlitrown@bidmc.harvard.edu; dbeach@bidmc.harvard.edu; klingon@bu.edu; rdavis@bidmc.harvard.edu; gyeh@hms.harvard.edu FU National Center for Complementary and Integrative Health, National Institutes of Health [R01AT006358] FX This study was supported by an award from the National Center for Complementary and Integrative Health, National Institutes of Health (Moy and Yeh, R01AT006358). NR 104 TC 1 Z9 2 U1 9 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 EI 1559-2030 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD NOV PY 2015 VL 45 BP 458 EP 467 DI 10.1016/j.cct.2015.09.004 PN B PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA DA4FJ UT WOS:000367755200044 PM 26362690 ER PT J AU Coronado, K AF Coronado, Kristine TI Comment on "Emergency Nurses' Perceptions of Discharge Processes for Patients Receiving Schedule II and III Medications for Pain Management in the Emergency Department" SO JOURNAL OF EMERGENCY NURSING LA English DT Editorial Material C1 [Coronado, Kristine] South Texas Vet Hlth Care Syst, Emergency Dept, San Antonio, TX 78229 USA. RP Coronado, K (reprint author), South Texas Vet Hlth Care Syst, Emergency Dept, San Antonio, TX 78229 USA. EM chickriss@yahoo.com NR 2 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 0099-1767 EI 1527-2966 J9 J EMERG NURS JI J. Emerg. Nurs. PD NOV PY 2015 VL 41 IS 6 BP 468 EP 469 DI 10.1016/j.jen.2015.08.001 PG 4 WC Emergency Medicine; Nursing SC Emergency Medicine; Nursing GA DA1TJ UT WOS:000367578100007 PM 26546544 ER PT J AU Stewart, MW Traylor, AC Bratzke, LC AF Stewart, Mara W. Traylor, Abigail C. Bratzke, Lisa C. TI Nutrition and Cognition in Older Adults With Heart Failure A Systematic Review SO JOURNAL OF GERONTOLOGICAL NURSING LA English DT Review ID DIETARY-FAT INTAKE; IMPAIRMENT; PERFORMANCE; RISK; DEMENTIA; DYSFUNCTION; ASSOCIATION; POPULATION; DECLINE; HEALTH AB Cognitive impairment is commonly observed in older adults with heart failure; nutrition is a possible contributing factor. The purpose of the current systematic review is to examine the relationship between nutrition and cognition in older adults with heart failure. A literature review was performed through August 2015 that examined published, peer-reviewed studies from PubMed, PsycINFO, CINAHL, and Web of Science. Four articles were selected for inclusion. Findings revealed that poorer nutritional habits were associated with poorer attention, executive functioning, and memory in older adults with heart failure. Nutritional biomarkers, including anemia, hyponatremia, hypokalemia, hyperglycemia, and hypoalbuminemia, were also associated with cognitive impairment. More research is needed to explore the relationship between nutrition and cognition in this population. Descriptive studies will inform scientists as they design and test nutritional interventions to optimize cognitive function in older adults with heart failure. C1 [Stewart, Mara W.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. [Traylor, Abigail C.] Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. [Bratzke, Lisa C.] Univ Wisconsin, Sch Nursing, Madison, WI USA. RP Stewart, MW (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace,Unit 2B, Madison, WI 53705 USA. EM Mara.Stewart@VA.gov OI Bratzke, Lisa/0000-0002-0321-4501 FU National Institute of Nursing Research of the National Institutes of Health (NIH) [R00NR012773] FX The authors have disclosed no potential conflicts of interest, financial or otherwise. Research reported in this article was supported by the National Institute of Nursing Research of the National Institutes of Health (NIH; award number R00NR012773 [L. C. Bratzke]). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 71 TC 1 Z9 1 U1 1 U2 3 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0098-9134 EI 1938-243X J9 J GERONTOL NURS JI J. Gerontol. Nurs. PD NOV PY 2015 VL 41 IS 11 BP 50 EP 59 DI 10.3928/00989134-20151015-06 PG 10 WC Geriatrics & Gerontology; Gerontology; Nursing SC Geriatrics & Gerontology; Nursing GA DA3JO UT WOS:000367693200007 PM 26505248 ER PT J AU Fanti, P Giustarini, D Rossi, R Cunningham, SED Folli, F Khazim, K Cornell, J Matteucci, E Bansal, S AF Fanti, Paolo Giustarini, Daniela Rossi, Ranieri Cunningham, Sue E. D. Folli, Franco Khazim, Khaled Cornell, John Matteucci, Elena Bansal, Shweta TI Dietary Intake of Proteins and Calories Is Inversely Associated With The Oxidation State of Plasma Thiols in End-Stage Renal Disease Patients SO JOURNAL OF RENAL NUTRITION LA English DT Article ID GELATINASE-ASSOCIATED LIPOCALIN; CHRONIC KIDNEY-DISEASE; MAINTENANCE HEMODIALYSIS-PATIENTS; SULFUR AMINO-ACIDS; METHIONINE RESTRICTION; OXIDANT STRESS; CARDIOVASCULAR-DISEASE; SKELETAL-MUSCLE; INFLAMMATION; FAILURE AB Objectives: Oxidative stress contributes to the pathogenesis of protein-energy wasting in maintenance hemodialysis (MHD) patients, but knowledge of specific effectors and mechanisms remains fragmented. Aim of the study was to define whether and how food intake is involved in the causal relationship between oxidative stress and protein-energy wasting. Methods: Seventy-one adult MHD patients and 24 healthy subjects (control) were studied cross-sectionally with analyses of diet record and of oxidative stress, as measured by a battery of plasma thiols including the protein sulfhydryl (-SH) group (PSH) levels (a marker of total protein-SH reducing capacity), the protein thiolation index (PTI, the ratio between disulfide, i.e., oxidized and reduced -SH groups in proteins), low molecular mass (LMM) thiols, LMM disulfides, and mixed LMM-protein disulfides. In addition, interleukin-6 (IL-6), albumin, C-reactive protein, and neutrophil gelatinase-associated lipocalin (NGAL) were measured as markers of inflammation. Results: The patients showed low energy (22.0 +/- 8.4 kcal/kg/day) and adequate protein (1.0 +/- 0.4 g/kg/day) intakes, high levels of cystine (CySS; patients vs. control: 113.5 [90.9-132.8] vs. 68.2 [56.2-75.7] mu M), cysteinylated proteins (CySSP; 216.0 [182.8-254.0] vs. 163.5 [150.0-195.5] mu M), and high PTI (0.76 [0.61-0.88] vs. 0.43 [0.40-0.54]; P < .001 in all comparisons). In patients, variation of CySSP was explained by a standard regression model (R = 0.775; P = .00001) that included significant contributions of protein intake (beta = -0.361), NGAL (beta = 0.387), age (beta = 0.295), and albumin (beta = 0.457). In the same model, variation of PTI (R = 0.624; P = .01) was explained by protein intake (beta = -0.384) and age (beta = 0.326) and NGAL (beta = 0.311). However, when PSH was entered as dependent variable (R = 0.730; P = .0001), only serum albumin (beta = 0.495) and age (beta = -0.280), but not dietary intake or NGAL, contributed to the model. Conclusions: In MHD, markers of thiol oxidation including CySSP and PTI show independent association with dietary intake and NGAL, whereas PSH, a marker of thiol-reducing capacity, did not associate with these same variables. The mechanism(s) responsible for inverse association between oxidative stress and food intake in MHD remain undefined. (C) 2015 by the National Kidney Foundation, Inc. All rights reserved. C1 [Fanti, Paolo; Bansal, Shweta] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. [Fanti, Paolo] South Texas Vet Hlth Care Syst, Renal Sect Med Serv, San Antonio, TX USA. [Giustarini, Daniela; Rossi, Ranieri] Univ Siena, Lab Pharmacol & Toxicol, Dept Life Sci, I-53100 Siena, Italy. [Cunningham, Sue E. D.] Univ Texas Hlth Sci Ctr San Antonio, Sch Hlth Profess, San Antonio, TX 78229 USA. [Folli, Franco] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Diabet, San Antonio, TX 78229 USA. [Khazim, Khaled] Western Galilee Hosp, Nephrol & Hypertens Unit, Nahariyya, Israel. [Cornell, John] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. [Matteucci, Elena] Univ Pisa, Dept Med, Pisa, Italy. RP Fanti, P (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Nephrol, 7703 Floyd Curl Dr,MSC 7882, San Antonio, TX 78229 USA. EM fanti@uthscsa.edu OI Giustarini, Daniela/0000-0003-4929-5316; folli, franco/0000-0001-9824-5222 FU CSRD VA [I01 CX000264]; NCATS NIH HHS [1UL TR001120, UL1 TR001120]; NCCIH NIH HHS [AT004490, R21 AT004490] NR 49 TC 2 Z9 2 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 1051-2276 EI 1532-8503 J9 J RENAL NUTR JI J. Renal Nutr. PD NOV PY 2015 VL 25 IS 6 BP 494 EP 503 DI 10.1053/j.jrn.2015.06.003 PG 10 WC Nutrition & Dietetics; Urology & Nephrology SC Nutrition & Dietetics; Urology & Nephrology GA DA0UC UT WOS:000367512000008 PM 26235932 ER PT J AU Sanchez, E Martin-Carreras, T Bornstein, G Wasyliw, CW Scherer, KF Bancroft, LW AF Sanchez, Edward Martin-Carreras, Teresa Bornstein, Gerald Wasyliw, Christopher W. Scherer, Kurt F. Bancroft, Laura W. TI Osteosarcoma of the Foot SO ORTHOPEDICS LA English DT Editorial Material ID TUMOR C1 [Sanchez, Edward] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Martin-Carreras, Teresa] Riverside Hosp, Newport News, VA USA. [Bornstein, Gerald] Florida Hosp, Orlando, FL USA. [Wasyliw, Christopher W.; Scherer, Kurt F.; Bancroft, Laura W.] Univ Cent Florida, Coll Med, Orlando, FL 32803 USA. RP Bancroft, LW (reprint author), Univ Cent Florida, Coll Med, 601 E Rollins, Orlando, FL 32803 USA. EM laura_bancroft.md@flhosp.org NR 18 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0147-7447 EI 1938-2367 J9 ORTHOPEDICS JI Orthopedics PD NOV PY 2015 VL 38 IS 11 BP 708 EP 711 DI 10.3928/01477447-20151016-02 PG 4 WC Orthopedics SC Orthopedics GA DA5JT UT WOS:000367840100019 ER PT J AU Maltz, JS Tison, GH Alley, HF Budinger, TF Owens, CD Olgin, J AF Maltz, Jonathan S. Tison, Geoffrey H. Alley, Hugh F. Budinger, Thomas F. Owens, Christopher D. Olgin, Jeffrey TI Measurement of brachial artery endothelial function using a standard blood pressure cuff SO PHYSIOLOGICAL MEASUREMENT LA English DT Article DE endothelial function; arterial function; cardiovascular disease; smooth muscle; reactive hyperemia; atherosclerosis ID FLOW-MEDIATED DILATION; SMOOTH-MUSCLE RELAXATION; CARDIOVASCULAR EVENTS; NITRIC-OXIDE; CORONARY ATHEROSCLEROSIS; DEPENDENT DILATION; VASCULAR-DISEASE; EUROPEAN-SOCIETY; PREDICTIVE-VALUE; TRANSIT TIMES AB The integrity of endothelial function in major arteries (EFMA) is a powerful independent predictor of heart attack and stroke. Existing ultrasound-based non-invasive assessment methods are technically challenging and suitable only for laboratory settings. EFMA, like blood pressure (BP), is both acutely and chronically affected by factors such as lifestyle and medication. Consequently, laboratory-based measurements cannot fully gauge the effects of medical interventions on EFMA. EFMA and BP have, arguably, comparable (but complementary) value in the assessment of cardiovascular health. Widespread deployment of EFMA assessment is thus a desirable clinical goal. To this end, we propose a device based on modifying the measurement protocol of a standard electronic sphygmomanometer. The protocol involves inflating the cuff to sub-diastolic levels to enable recording of the pulse waveform before and after vasodilatory stimulus. The mechanical unloading of the arterial wall provided by the cuff amplifies the distension that occurs with each pulse, which is measured as a pressure variation in the cuff. We show that the height of the rising edge of each pulse is proportional to the change in lumen area between diastole and systole. This allows the effect of vasodilatory stimuli on the artery to be measured with high sensitivity. We compare the proposed cuff flow-mediated dilation (cFMD) method to ultrasound flow-mediated dilation (uFMD). We find significant correlation (r = 0.55, p = 0.003, N = 27) between cFMD- and uFMD-based metrics obtained when the release of a 5 min cuff occlusion is employed to induce endothelial stimulus via reactive hyperemia. cFMD is approximately proportional to the square of uFMD, representing a typical increase in sensitivity to vasodilation of 300-600%. This study illustrates the potential for an individual to conveniently measure his/her EFMA by using a low-cost reprogrammed home sphygmomanometer. C1 [Maltz, Jonathan S.; Budinger, Thomas F.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Dept Struct Biol & Imaging, Berkeley, CA 94720 USA. [Tison, Geoffrey H.; Olgin, Jeffrey] Univ Calif San Francisco, Div Cardiol, San Francisco, CA 94143 USA. [Tison, Geoffrey H.; Olgin, Jeffrey] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Alley, Hugh F.; Owens, Christopher D.] San Francisco VA Med Ctr, Div Vasc & Endovasc Surg, San Francisco, CA 94143 USA. [Alley, Hugh F.; Owens, Christopher D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Maltz, JS (reprint author), Cyclotron Rd,Mail Stop 55R0121, Berkeley, CA 94720 USA. EM jon@eecs.berkeley.edu FU US Department of Energy [DE-AC02-05CH11231]; Berkeley Lab Innovation Grant; Office of Science, Office of Basic Energy Sciences of the US Department of Energy [DE-AC02-05CH11231]; United States Government FX Funding for this work was provided, in part, by a Berkeley Lab Innovation Grant. The support and advice of Pam Seidenman and Bill Shelander of the Innovation and Partnerships Office is greatly appreciated.; This work was supported by the Director, Office of Science, Office of Basic Energy Sciences, of the US Department of Energy under Contract No. DE-AC02-05CH11231.; this document was prepared as an account of work sponsored by the United States Government. While this document is believed to contain correct information, neither the United States Government nor any agency thereof, nor the Regents of the University of California, nor any of their employees, makes any warranty, express or implied, or assumes any legal responsibility for the accuracy, completeness, or usefulness of any information, apparatus, product, or process disclosed, or represents that its use would not infringe privately owned rights. Reference herein to any specific commercial product, process, or service by its trade name, trademark, manufacturer, or otherwise, does not necessarily constitute or imply its endorsement, recommendation, or favoring by the United States Government or any agency thereof, or the Regents of the University of California. The views and opinions of authors expressed herein do not necessarily state or reflect those of the United States Government or any agency thereof or the Regents of the University of California.; This manuscript has been authored by an author at Lawrence Berkeley National Laboratory under Contract No. DE-AC02-05CH11231 with the US Department of Energy. The US Government retains, and the publisher, by accepting the article for publication, acknowledges, that the US Government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or reproduce the published form of this manuscript, or allow others to do so, for US Government purposes. NR 50 TC 0 Z9 0 U1 0 U2 4 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0967-3334 EI 1361-6579 J9 PHYSIOL MEAS JI Physiol. Meas. PD NOV PY 2015 VL 36 IS 11 BP 2247 EP 2268 DI 10.1088/0967-3334/36/11/2247 PG 22 WC Biophysics; Engineering, Biomedical; Physiology SC Biophysics; Engineering; Physiology GA DA5LK UT WOS:000367844400003 PM 26393958 ER PT J AU Ponce, J Nguyen, NT Hutter, M Sudan, R Morton, JM AF Ponce, Jaime Nguyen, Ninh T. Hutter, Matthew Sudan, Ranjan Morton, John M. TI American Society for Metabolic and Bariatric Surgery estimation of bariatric surgery procedures in the United States, 2011-2014 SO SURGERY FOR OBESITY AND RELATED DISEASES LA English DT Article DE Bariatric surgery numbers; ASMBS ID OBESITY C1 [Ponce, Jaime] Chattanooga Bariatr, Chattanooga, TN USA. [Nguyen, Ninh T.] Univ Calif Irvine, Irvine Med Ctr, Dept Surg, Orange, CA 92668 USA. [Hutter, Matthew] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Sudan, Ranjan] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Morton, John M.] Stanford Univ, Dept Surg, Palo Alto, CA 94304 USA. RP Ponce, J (reprint author), 7405 Shallowford Rd,Suite 160, Chattanooga, TN 37421 USA. EM JPonceMD@gmail.com NR 7 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1550-7289 EI 1878-7533 J9 SURG OBES RELAT DIS JI Surg. Obes. Relat. Dis. PD NOV-DEC PY 2015 VL 11 IS 6 BP 1199 EP 1200 DI 10.1016/j.soard.2015.08.496 PG 2 WC Surgery SC Surgery GA CZ9KK UT WOS:000367416300001 PM 26476493 ER PT J AU Schreuder, WH Peacock, ZS AF Schreuder, Willem H. Peacock, Zachary S. TI ORAL AND MAXILLOFACIAL SURGERY Antiplatelet therapy and exodontia SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article DE Tooth extraction; exodontia; antiplatelet; aspirin; NSAID; thienopyridine; clopidogrel; dipyridamole; postoperative bleeding ID LOW-DOSE ASPIRIN; PERCUTANEOUS CORONARY INTERVENTION; CLINICAL-PRACTICE GUIDELINES; INVASIVE DENTAL TREATMENT; ED AMERICAN-COLLEGE; CONTROLLED-TRIAL; PREMATURE DISCONTINUATION; ANTITHROMBOTIC THERAPY; SECONDARY PREVENTION; PLATELET-FUNCTION AB Background. This is a review of the management considerations regarding exodontia for patients taking antithrombotic medications that affect platelet function or aggregation. Methods. The authors reviewed the literature, focusing on the indications and mechanisms of antiplatelet therapy and the perioperative management of patients taking these agents who require exodontia or other dentoalveolar surgery. Results. Dentists making management decisions regarding patients taking antiplatelet therapy should consider the patient's risk of experiencing perioperative hemorrhage against the risk of experiencing complications associated with thromboembolic events. The risk of perioperative bleeding complications is low for patients taking single or dual antiplatelet therapy. Intraoperative and postoperative bleeding can be controlled with local hemostatic measures. Conclusion. For patients taking antiplatelet medication, bleeding risk for exodontia is generally lower than the risk of experiencing thromboembolic events owing to cessation of therapy. Practical Implications. Dentists can safely complete exodontia in patients who continue taking antiplatelet therapy. The dentist should consult the patient's prescribing physician before considering altering the patient's antiplatelet therapy regimen. C1 [Schreuder, Willem H.; Peacock, Zachary S.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Schreuder, Willem H.; Peacock, Zachary S.] Harvard Univ, Sch Dent Med, Boston, MA 02114 USA. RP Peacock, ZS (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St, Boston, MA 02114 USA. NR 47 TC 0 Z9 0 U1 2 U2 8 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 EI 1943-4723 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD NOV PY 2015 VL 146 IS 11 BP 851 EP 856 DI 10.1016/j.adaj.2015.04.024 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA CZ8HO UT WOS:000367341000017 PM 26514891 ER PT J AU Kaye, AD Manchikanti, L Abdi, S Atluri, S Bakshi, S Benyamin, R Boswell, MV Buenaventura, R Candido, KD Cordner, HJ Datta, S Doulatram, G Gharibo, CG Grami, V Gupta, S Jha, S Kaplan, ED Malla, Y Mann, DP Nampiaparampil, DE Racz, G Raj, P Rana, MV Sharma, ML Singh, V Soin, A Staats, PS Vallejo, R Wargo, BW Hirsch, JA AF Kaye, Alan D. Manchikanti, Laxmaiah Abdi, Salahadin Atluri, Sairam Bakshi, Sanjay Benyamin, Ramsin Boswell, Mark V. Buenaventura, Ricardo Candido, Kenneth D. Cordner, Harold J. Datta, Sukdeb Doulatram, Gulshan Gharibo, Christopher G. Grami, Vahid Gupta, Sanjeeva Jha, Sachin Kaplan, Eugene D. Malla, Yogesh Mann, Dharam P. Nampiaparampil, Devi E. Racz, Gabor Raj, Prithvi Rana, Maunak V. Sharma, Manohar Lal Singh, Vijay Soin, Amol Staats, Peter S. Vallejo, Ricardo Wargo, Bradley W. Hirsch, Joshua A. TI Efficacy of Epidural Injections in Managing Chronic Spinal Pain: A Best Evidence Synthesis SO PAIN PHYSICIAN LA English DT Review DE Chronic pain; spinal pain; epidural injections; local anesthetic; steroids; interlaminar epidural injections; caudal epidural injections; transforaminal epidural injections ID LOW-BACK-PAIN; LUMBAR RADICULAR PAIN; ACTIVE-CONTROL TRIAL; 2-YEAR FOLLOW-UP; RANDOMIZED-CONTROLLED-TRIAL; CLINICALLY IMPORTANT DIFFERENCE; BONE-MINERAL DENSITY; DOUBLE-BLIND TRIAL; EXTRADURAL CORTICOSTEROID INJECTION; PREVENT NEUROLOGIC COMPLICATIONS AB Background: Epidural injections have been used since 1901 in managing low back pain and sciatica. Spinal pain, disability, health, and economic impact continue to increase, despite numerous modalities of interventions available in managing chronic spinal pain. Thus far, systematic reviews performed to assess the efficacy of epidural injections in managing chronic spinal pain have yielded conflicting results. Objective: To evaluate and update the clinical utility of the efficacy of epidural injections in managing chronic spinal pain. Study Design: A systematic review of randomized controlled trials of epidural injections in managing chronic spinal pain. Methods: In this systematic review, randomized trials with a placebo control or an active-control design were included. The outcome measures were pain relief and functional status improvement. The quality of each individual article was assessed by Cochrane review criteria, as well as the Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB). Best evidence synthesis was conducted based on the qualitative level of evidence (Level I to V). Data sources included relevant literature identified through searches of PubMed for a period starting in 1966 through August 2015; Cochrane reviews; and manual searches of the bibliographies of known primary and review articles. Results: A total of 52 trials met inclusion criteria. Meta-analysis was not feasible. The evidence in managing lumbar disc herniation or radiculitis is Level II for long-term improvement either with caudal, interlaminar, or transforaminal epidural injections with no significant difference among the approaches. The evidence is Level II for long-term management of cervical disc herniation with interlaminar epidural injections. The evidence is Level II to III in managing thoracic disc herniation with an interlaminar approach. The evidence is Level II for caudal and lumbar interlaminar epidural injections with Level III evidence for lumbar transforaminal epidural injections for lumbar spinal stenosis. The evidence is Level II for cervical spinal stenosis management with an interlaminar approach. The evidence is Level II for axial or discogenic pain without facet arthropathy or disc herniation treated with caudal or lumbar interlaminar injections in the lumbar region; whereas it is Level II in the cervical region treated with cervical interlaminar epidural injections. The evidence for post lumbar surgery syndrome is Level II with caudal epidural injections and for post cervical surgery syndrome it is Level II with cervical interlaminar epidural injections. Limitations: Even though this is a large systematic review with inclusion of a large number of randomized controlled trials, the paucity of high quality randomized trials literature continues to confound the evidence. Conclusion: This systematic review, with an assessment of the quality of manuscripts and outcome parameters, shows the efficacy of epidural injections in managing a multitude of chronic spinal conditions. C1 [Kaye, Alan D.] LSU Hlth Sci Ctr, New Orleans, LA USA. [Manchikanti, Laxmaiah; Malla, Yogesh] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah; Boswell, Mark V.] Univ Louisville, Louisville, KY 40292 USA. [Abdi, Salahadin] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Atluri, Sairam] Tristate Spine Care Inst, Cincinnati, OH USA. [Bakshi, Sanjay] Manhattan Spine & Pain Med, New York, NY USA. [Benyamin, Ramsin; Vallejo, Ricardo] Millennium Pain Ctr, Bloomington, IL USA. [Benyamin, Ramsin] Univ Illinois, Urbana, IL 61801 USA. [Buenaventura, Ricardo] Pain Relief Dayton, Centerville, OH USA. [Buenaventura, Ricardo] Wright State Univ, Sch Med, Dayton, OH USA. [Candido, Kenneth D.] Advocate Illinois Mason Med Ctr, Chicago, IL USA. [Candido, Kenneth D.] Univ Illinois, Coll Med, Chicago, IL USA. [Cordner, Harold J.] Florida Pain Management Associates, Sebastian, FL USA. [Datta, Sukdeb] Datta Endoscop Back Surg & Pain Ctr, New York, NY USA. [Datta, Sukdeb] Mt Sinai Sch Med, New York, NY USA. [Doulatram, Gulshan] Univ Texas Med Branch, Galveston, TX 77555 USA. [Gharibo, Christopher G.] NYU Sch Med, NYU Langone Hosp Joint Dis, New York, NY USA. [Grami, Vahid] Geisinger Med Ctr, Intervent Pain Ctr Woodbine, Danville, PA 17822 USA. [Gupta, Sanjeeva] Bradford Teaching Hosp NHS Fdn Trust, Bradford, W Yorkshire, England. [Jha, Sachin] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Kaplan, Eugene D.] Optimum Hlth Med Grp, Clifton Pk, NY USA. [Kaplan, Eugene D.] Kaplan Headache & Facial Pain Ctr, Clifton Pk, NY USA. [Kaplan, Eugene D.] Comprehens Intervent Pain Management Ctr, Clifton Pk, NY USA. [Mann, Dharam P.] Garden State Pain Management, Whiting, NJ USA. [Nampiaparampil, Devi E.] NYU, Sch Med, New York, NY USA. [Racz, Gabor; Raj, Prithvi] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA. [Rana, Maunak V.] Advocate Illinois Mason Med Ctr, Chicago, IL USA. [Rana, Maunak V.] Univ Illinois, Chicago, IL USA. [Sharma, Manohar Lal] Walton Ctr Neurol & Neurosurg NHS Fdn Trust, Liverpool, Merseyside, England. [Singh, Vijay] Spine Pain Diagnost Associates, Niagara, WI USA. [Soin, Amol] Ohio Pain Clin, Centerville, OH USA. [Staats, Peter S.] Premier Pain Ctr, Shrewsbury, NJ USA. [Staats, Peter S.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Vallejo, Ricardo] Illinois State Univ, Normal, IL 61761 USA. [Wargo, Bradley W.] Mary Greeley Med Ctr, Dept Pain Med, McFarland Clin, Ames, IA USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Univ, Sch Med, Boston, MA USA. RP Kaye, AD (reprint author), LSU Sch Med T6M5, Dept Anesthesiol, 1542 Tulane Ave,Room 656, New Orleans, LA 70112 USA. EM alankaye44@hotmail.com FU Sucampo Pharmaceuticals; Boston Scientific; St Jude; Spinal Modulation; Vertos FX Dr. Benyamin is a consultant and lecturer for Boston Scientific and Kimberly Clark. Dr. Datta receives research support from Sucampo Pharmaceuticals and an honorarium from Smith and Nephew Dr. Gupta has been paid honorarium for presenting at meetings and teaching on the interventional pain medicine cadaver courses and by pharmaceutical companies for presenting to health care professionals. Pharmaceutical companies and companies that manufacture equipment used in pain medicine have supported meetings organized by Dr S Gupta. Dr. Alan Kaye is a speaker for Depomed, Inc. Dr. Manchikanti has provided limited consulting services to Semnur Pharmaceuticals, Incorporated, which is developing nonparticulate steroids. Dr. Racz is a Consultant for and has family ownership of Epimed International, is a Consultant to Cosman RF company, and has Medtronic patent issues. Dr Staats Is a Consultant for Medtronic, Boston Scientific, St Jude, Electrocore Medical, Currently is involved in research funded by Boston Scientific, St Jude, Spinal Modulation, Vertos. NR 267 TC 15 Z9 15 U1 6 U2 13 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD NOV-DEC PY 2015 VL 18 IS 6 BP E939 EP E1004 PG 66 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA DA0ZD UT WOS:000367525200001 PM 26606031 ER PT J AU Danne, T Laffel, L Domenger, C Pilorget, V Candelas, C Phillip, M Mazza, C Anderson, B Hanas, R Waldron, S Beck, R Mathieu, C Calvi-Gries, F AF Danne, Thomas Laffel, Lori Domenger, Catherine Pilorget, Valerie Candelas, Christophe Phillip, Moshe Mazza, Carmen Anderson, Barbara Hanas, Ragnar Waldron, Sheridan Beck, Roy Mathieu, Chantal Calvi-Gries, Francoise TI Treatment Characteristics and Diabetes Management of 5960 Children, Youngsters and young Adults with Type-1-Diabetes (T1D): the world wide TEENS-Study SO WIENER KLINISCHE WOCHENSCHRIFT LA German DT Meeting Abstract C1 [Danne, Thomas] Auf Bult, Kinder & Jugendkrankenhaus, Hannover, Germany. [Laffel, Lori] Joslin Diabet Ctr, Boston, MA 02215 USA. [Domenger, Catherine] Sanofi, Paris, France. [Pilorget, Valerie; Candelas, Christophe] Sanofi, Chilly Mazarin, France. [Phillip, Moshe] Schneider Childrens Med Ctr Israel, Petah Tiqwa, Israel. [Mazza, Carmen] Hosp Pediat JP Garrahen, Buenos Aires, DF, Argentina. [Anderson, Barbara] Baylor Coll Med, Houston, TX 77030 USA. [Hanas, Ragnar] Gothenburg Univ, Gothenburg, Sweden. [Waldron, Sheridan] West Midlands Strateg Clin Network, Birmingham, W Midlands, England. [Beck, Roy] Jaeb Ctr Hlth Res, Tampa, FL USA. [Mathieu, Chantal] Univ Hosp ZU, Leuven, Belgium. [Calvi-Gries, Francoise] AtlanStat, Nantes, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0043-5325 EI 1613-7671 J9 WIEN KLIN WOCHENSCHR JI Wien. Klin. Wochen. PD NOV PY 2015 VL 127 SU 4 BP S139 EP S139 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA DA0BK UT WOS:000367461500019 ER PT J AU Laffel, L Domenger, C Pilorget, V Candelas, C Danne, T Phillip, M Mazza, C Anderson, B Hanas, R Waldron, S Beck, R Mathieu, C AF Laffel, Lori Domenger, Catherine Pilorget, Valerie Candelas, Christophe Danne, Thomas Phillip, Moshe Mazza, Carmen Anderson, Barbara Hanas, Ragnar Waldron, Sheridan Beck, Roy Mathieu, Chantal TI Acute Complications and Blood Sugar Control in Children, Youngsters and young Adults with Type-1-Diabetes (T1D): the world wide TEENS- Study SO WIENER KLINISCHE WOCHENSCHRIFT LA German DT Meeting Abstract C1 [Laffel, Lori] Joslin Diabet Ctr, Boston, MA 02215 USA. [Domenger, Catherine] Sanofi, Paris, France. [Pilorget, Valerie; Candelas, Christophe] Sanofi, Chilly Mazarin, France. [Danne, Thomas] Auf Bult, Kinder & Jugendkrankenhaus, Hannover, Germany. [Phillip, Moshe] Schneider Childrens Med Ctr Israel, Petah Tiqwa, Israel. [Mazza, Carmen] Hosp Pediat JP Garrahan, Buenos Aires, DF, Argentina. [Anderson, Barbara] Baylor Coll Med, Houston, TX 77030 USA. [Hanas, Ragnar] Gothenburg Univ, Gothenburg, Sweden. [Waldron, Sheridan] West Midlands Strateg Clin Network, Birmingham, W Midlands, England. [Beck, Roy] Jaeb Ctr Hlth Res, Tampa, FL USA. [Mathieu, Chantal] Univ Hosp ZU, Leuven, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0043-5325 EI 1613-7671 J9 WIEN KLIN WOCHENSCHR JI Wien. Klin. Wochen. PD NOV PY 2015 VL 127 SU 4 BP S140 EP S140 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA DA0BK UT WOS:000367461500020 ER PT J AU Phillip, M Laffel, L Domenger, C Pilorget, V Candelas, C Danne, T Mazza, C Anderson, B Hanas, R Waldron, S Beck, R Mathieu, C AF Phillip, Moshe Laffel, Lori Domenger, Catherine Pilorget, Valerie Candelas, Christophe Danne, Thomas Mazza, Carmen Anderson, Barbara Hanas, Ragnar Waldron, Sheridan Beck, Roy Mathieu, Chantal TI Results of the Europe Subgroup: Disease Management and Results in Children, Youngsters and young Adults with Type-1-Diabetes (T1D): the world wide TEENS-Study SO WIENER KLINISCHE WOCHENSCHRIFT LA German DT Meeting Abstract C1 [Phillip, Moshe] Schneider Childrens Med Ctr Israel, Petah Tiqwa, Israel. [Laffel, Lori] Joslin Diabet Ctr, Boston, MA 02215 USA. [Domenger, Catherine] Sanofi, Paris, France. [Pilorget, Valerie; Candelas, Christophe] Sanofi, Chilly Mazarin, France. [Danne, Thomas] Auf Bult, Kinder & Jugendkrankenhaus, Hannover, Germany. [Mazza, Carmen] Hosp Pediat JP Garrahan, Buenos Aires, DF, Argentina. [Anderson, Barbara] Baylor Coll Med, Houston, TX 77030 USA. [Hanas, Ragnar] Gothenburg Univ, Gothenburg, Sweden. [Waldron, Sheridan] West Midlands Strateg Clin Network, Birmingham, W Midlands, England. [Beck, Roy] Jaeb Ctr Hlth Res, Tampa, FL USA. [Mathieu, Chantal] Univ Hosp ZU, Leuven, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0043-5325 EI 1613-7671 J9 WIEN KLIN WOCHENSCHR JI Wien. Klin. Wochen. PD NOV PY 2015 VL 127 SU 4 BP S140 EP S140 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA DA0BK UT WOS:000367461500021 ER PT J AU Kimball, AB Schenfeld, J Accortt, NA Anthony, MS Rothman, KJ Pariser, D AF Kimball, A. B. Schenfeld, J. Accortt, N. A. Anthony, M. S. Rothman, K. J. Pariser, D. TI Cohort study of malignancies and hospitalized infectious events in treated and untreated patients with psoriasis and a general population in the United States SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID CANCER-RISK; RATES; METAANALYSIS; ARTHRITIS; MORTALITY; LYMPHOMA; SAFETY; CARE AB Background Psoriasis is associated with risk of malignancy. Some psoriasis treatments may increase the risk of hospitalized infectious events (HIEs). Objectives To evaluate rates of malignancies and HIEs in patients with psoriasis. Methods This retrospective cohort study utilized data from MarketScan (R) databases. Cohorts included adult general population (GP), patients with psoriasis, and patients with psoriasis treated with nonbiologics, adalimumab, etanercept, infliximab or phototherapy. Outcomes included incidence rates (IRs) per 10 000 person-years observation (PYO) for all malignancies excluding nonmelanoma skin cancer (NMSC), lymphoma, NMSC, and per 10 000 person-years of exposure (PYE) for HIEs. Results Incidence rates [95% confidence interval (CI)] for all malignancies except NMSC were 129 (127-130) and 142 (135-149) for GP (PYO = 51 071 587) and psoriasis (PYO = 119 432) cohorts, respectively; 10.9 (10.5-11.3) and 12.9 (10.9-14.8) for lymphoma; and 145 (144-147) and 180 (173-188) for NMSC. Rates for all malignancies excluding NMSC were similar among treatments but variable for lymphoma and NMSC. IRs (95% CI) for HIEs were 332 (256-408) for the nonbiologic cohort (PYE = 3528); 288 (206-370) for etanercept (PYE = 6563); 325 (196-455) for adalimumab (PYE = 2772); 521 (278-765) for infliximab (PYE = 1058); and 334 (242-427) for phototherapy (PYE = 1797). IRs for HIEs were lowest for etanercept and higher in patients on baseline systemic corticosteroids across treatment cohorts. Conclusions Malignancy rates were higher in patients with psoriasis than the GP, but these treatments did not appear to increase malignancy risk. C1 [Kimball, A. B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Schenfeld, J.] DOCS Global Inc, N Wales, PA USA. [Accortt, N. A.; Anthony, M. S.] Amgen Inc, Thousand Oaks, CA 91320 USA. [Rothman, K. J.] RTI Int, Res Triangle Pk, NC USA. [Pariser, D.] Eastern Virginia Med Sch, Norfolk, VA 23501 USA. [Pariser, D.] Virginia Clin Res Inc, Norfolk, VA USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 50 Staniford St 240, Boston, MA 02114 USA. EM harvardskinstudies@partners.org FU Immunex of Amgen Inc. FX This study was funded by Immunex, a wholly owned subsidiary of Amgen Inc. Amgen was involved in data collection, data analysis, and medical writing assistance. NR 28 TC 2 Z9 2 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD NOV PY 2015 VL 173 IS 5 BP 1183 EP 1190 PG 8 WC Dermatology SC Dermatology GA CX7VD UT WOS:000365910100024 PM 26265015 ER PT J AU Liu, H Li, W Rose, ME Hickey, RW Chen, J Uechi, GT Balasubramani, M Day, BW Patel, KV Graham, SH AF Liu, H. Li, W. Rose, M. E. Hickey, R. W. Chen, J. Uechi, G. T. Balasubramani, M. Day, B. W. Patel, K. V. Graham, S. H. TI The point mutation UCH-L1 C152A protects primary neurons against cyclopentenone prostaglandin-induced cytotoxicity: implications for post-ischemic neuronal injury SO CELL DEATH & DISEASE LA English DT Article ID TERMINAL HYDROLASE L1; PARKINSONS-DISEASE SUSCEPTIBILITY; MUTANT LOX SITES; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); ENDOGENOUS ELECTROPHILE; CELLULAR-PROTEINS; CARDIAC-ARREST; UCHL1; GENE; CELLS AB Cyclopentenone prostaglandins (CyPGs), such as 15-deoxy-Delta(12,14)-prostaglandin J(2) (15dPGJ2), are reactive prostaglandin metabolites exerting a variety of biological effects. CyPGs are produced in ischemic brain and disrupt the ubiquitin-proteasome system (UPS). Ubiquitin-C-terminal hydrolase L1 (UCH-L1) is a brain-specific deubiquitinating enzyme that has been linked to neurodegenerative diseases. Using tandem mass spectrometry (MS) analyses, we found that the C152 site of UCH-L1 is adducted by CyPGs. Mutation of C152 to alanine (C152A) inhibited CyPG modification and conserved recombinant UCH-L1 protein hydrolase activity after 15dPGJ2 treatment. A knock-in (KI) mouse expressing the UCH-L1 C152A mutation was constructed with the bacterial artificial chromosome (BAC) technique. Brain expression and distribution of UCH-L1 in the KI mouse was similar to that of wild type (WT) as determined by western blotting. Primary cortical neurons derived from KI mice were resistant to 15dPGJ2 cytotoxicity compared with neurons from WT mice as detected by the WST-1 cell viability assay and caspase-3 and poly ADP ribose polymerase (PARP) cleavage. This protective effect was accompanied with significantly less ubiquitinated protein accumulation and aggregation as well as less UCH-L1 aggregation in C152A KI primary neurons after 15dPGJ2 treatment. Additionally, 15dPGJ2-induced axonal injury was also significantly attenuated in KI neurons as compared with WT. Taken together, these studies indicate that UCH-L1 function is important in hypoxic neuronal death, and the C152 site of UCH-L1 has a significant role in neuronal survival after hypoxic/ischemic injury. C1 [Liu, H.; Li, W.; Rose, M. E.; Graham, S. H.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA 15240 USA. [Liu, H.; Li, W.; Rose, M. E.; Chen, J.; Patel, K. V.; Graham, S. H.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Hickey, R. W.] Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15261 USA. [Uechi, G. T.; Balasubramani, M.; Day, B. W.] Univ Pittsburgh, Genom & Prote Core Labs, Pittsburgh, PA USA. [Day, B. W.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. RP Graham, SH (reprint author), VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Res Off Bldg 30,Mail Code 151,Univ Dr, Pittsburgh, PA 15240 USA. EM Steven.Graham@va.gov FU VA Merit Review program; National Institutes of Health NINDS [R01NS37549]; Cancer Center Support Grant, National Cancer Institute [P30CA047904] FX This work was supported by the VA Merit Review program (SHG) and National Institutes of Health NINDS R01NS37549 (SHG). Work performed by the Biomedical Mass Spectrometry Center was supported in part by the Cancer Center Support Grant P30CA047904, National Cancer Institute. NR 55 TC 6 Z9 6 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-4889 J9 CELL DEATH DIS JI Cell Death Dis. PD NOV PY 2015 VL 6 AR e1966 DI 10.1038/cddis.2015.323 PG 11 WC Cell Biology SC Cell Biology GA CZ5PU UT WOS:000367155300005 PM 26539913 ER PT J AU Matsumoto, H Murakami, Y Kataoka, K Notomi, S Mantopoulos, D Trichonas, G Miller, JW Gregory, MS Ksander, BR Marshak-Rothstein, A Vavvas, DG AF Matsumoto, H. Murakami, Y. Kataoka, K. Notomi, S. Mantopoulos, D. Trichonas, G. Miller, J. W. Gregory, M. S. Ksander, B. R. Marshak-Rothstein, A. Vavvas, D. G. TI Membrane-bound and soluble Fas ligands have opposite functions in photoreceptor cell death following separation from the retinal pigment epithelium SO CELL DEATH & DISEASE LA English DT Article ID APOPTOSIS-INDUCING FACTOR; EXPERIMENTAL-MODEL; CD95 LIGAND; IN-VIVO; DETACHMENT; MACROPHAGES; DEGENERATION; ACTIVATION; RECEPTOR; PATHWAY AB Fas ligand (FasL) triggers apoptosis of Fas-positive cells, and previous reports described FasL-induced cell death of Fas-positive photoreceptors following a retinal detachment. However, as FasL exists in membrane-bound (mFasL) and soluble (sFasL) forms, and is expressed on resident microglia and infiltrating monocyte/macrophages, the current study examined the relative contribution of mFasL and sFasL to photoreceptor cell death after induction of experimental retinal detachment in wild-type, knockout (FasL -/-), and mFasL-only knock-in (Delta CS) mice. Retinal detachment in FasL -/- mice resulted in a significant reduction of photoreceptor cell death. In contrast, Delta CS mice displayed significantly more apoptotic photoreceptor cell death. Photoreceptor loss in Delta CS mice was inhibited by a subretinal injection of recombinant sFasL. Thus, Fas/FasL-triggered cell death accounts for a significant amount of photoreceptor cell loss following the retinal detachment. The function of FasL was dependent upon the form of FasL expressed: mFasL triggered photoreceptor cell death, whereas sFasL protected the retina, indicating that enzyme-mediated cleavage of FasL determines, in part, the extent of vision loss following the retinal detachment. Moreover, it also indicates that treatment with sFasL could significantly reduce photoreceptor cell loss in patients with retinal detachment. C1 [Matsumoto, H.; Murakami, Y.; Kataoka, K.; Notomi, S.; Mantopoulos, D.; Trichonas, G.; Miller, J. W.; Vavvas, D. G.] Harvard Univ, Sch Med, Dept Ophthalmol, Angiogenesis Lab,Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Gregory, M. S.; Ksander, B. R.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm,Schepens Eye Res I, Boston, MA 02114 USA. [Marshak-Rothstein, A.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. RP Vavvas, DG (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, 325 Cambridge St, Boston, MA 02114 USA. EM vavvas@meei.harvard.edu RI Kataoka, Keiko/B-2806-2016 OI Kataoka, Keiko/0000-0002-8795-6536 FU Foundation Lions Eye Research Fund; Yeatts Family Foundation; Loefffler Family Foundation; Macula Society; Bausch & Lomb Vitreoretinal Fellowship; Japan Society for the Promotion of Science; Novartis Pharma K.K. Tokyo, Japan; RPB Physician Scientist Award; Research to Prevent Blindness Foundation; NEI [R21EY023079-01/A1, EY014104] FX We thank Wendy Chao for her support in critical review. This work was supported by Foundation Lions Eye Research Fund (DGV); The Yeatts Family Foundation (DGV and JWM); The Loefffler Family Foundation (DGV and JWM); 2013 Macula Society Research Grant award (DGV); Bausch & Lomb Vitreoretinal Fellowship (HM); Grant-in-Aid for Young Scientists (B) from Japan Society for the Promotion of Science (HM); Grant-in-Aid from Novartis Pharma K.K. Tokyo, Japan (HM); a RPB Physician Scientist Award (DGV) and unrestricted grant (JWM) from the Research to Prevent Blindness Foundation; NEI R21EY023079-01/A1 (DGV) and NEI grant EY014104 (MEEI Core Grant). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Eye Institute or the National Institutes of Health. NR 51 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-4889 J9 CELL DEATH DIS JI Cell Death Dis. PD NOV PY 2015 VL 6 AR e1986 DI 10.1038/cddis.2015.334 PG 9 WC Cell Biology SC Cell Biology GA CZ5PU UT WOS:000367155300022 PM 26583327 ER PT J AU Azadbakht, H Parkes, LM Haroon, HA Augath, M Logothetis, NK de Crespigny, A D'Arceuil, HE Parker, GJM AF Azadbakht, Hojjatollah Parkes, Laura M. Haroon, Hamied A. Augath, Mark Logothetis, Nikos K. de Crespigny, Alex D'Arceuil, Helen E. Parker, Geoffrey J. M. TI Validation of High-Resolution Tractography Against In Vivo Tracing in the Macaque Visual Cortex SO CEREBRAL CORTEX LA English DT Article DE diffusion imaging; macaque; tractography; validation; visual cortex ID DIFFUSION-WEIGHTED MRI; WHITE-MATTER; FIBER TRACKING; FUNCTIONAL MRI; SPHERICAL DECONVOLUTION; CEREBRAL-CORTEX; TENSOR; BRAIN; CONNECTIONS; PHANTOM AB Diffusion magnetic resonance imaging (MRI) allows for the noninvasive in vivo examination of anatomical connections in the human brain, which has an important role in understanding brain function. Validation of this technique is vital, but has proved difficult due to the lack of an adequate gold standard. In this work, the macaque visual system was used as a model as an extensive body of literature of in vivo and postmortem tracer studies has established a detailed understanding of the underlying connections. We performed probabilistic tractography on high angular resolution diffusion imaging data of 2 ex vivo, in vitro macaque brains. Comparisons were made between identified connections at different thresholds of probabilistic connection "strength," and with various tracking optimization strategies previously proposed in the literature, and known connections from the detailed visual system wiring map described by Felleman and Van Essen (1991; FVE91). On average, 74% of connections that were identified by FVE91 were reproduced by performing the most successfully optimized probabilistic diffusion MRI tractography. Further comparison with the results of a more recent tracer study (Markov et al. 2012) suggests that the fidelity of tractography in estimating the presence or absence of interareal connections may be greater than this. C1 [Azadbakht, Hojjatollah; Parkes, Laura M.; Haroon, Hamied A.; Logothetis, Nikos K.; Parker, Geoffrey J. M.] Univ Manchester, Ctr Imaging Sci, Fac Med & Human Sci, Manchester Acad Hlth Sci Ctr, Manchester M13 9PT, Lancs, England. [Augath, Mark; Logothetis, Nikos K.] Max Planck Inst Biol Cybernet, D-72076 Tubingen, Germany. [de Crespigny, Alex; D'Arceuil, Helen E.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Charlestown, MA USA. RP Parkes, LM (reprint author), Univ Manchester, Ctr Imaging Sci, Stopford Bldg,Oxford Rd, Manchester M13 9PT, Lancs, England. EM laura.parkes@manchester.ac.uk RI Haroon, Hamied/D-7732-2015; OI Haroon, Hamied/0000-0002-3506-8430; Parkes, Laura/0000-0001-6488-507X; Parker, Geoffrey/0000-0003-2934-2234 FU UK's BBSRC [BB/E002226/1]; CONNECT consortium; EU FP7 framework; RCUK grant FX This work was supported by the UK's BBSRC (grant BB/E002226/1) and the CONNECT consortium, and funded by the future and emerging technologies (FET) program of the EU FP7 framework. Funding to pay the Open Access publication charges for this article was provided by an RCUK grant to the University of Manchester. NR 63 TC 8 Z9 8 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD NOV PY 2015 VL 25 IS 11 BP 4299 EP 4309 DI 10.1093/cercor/bhu326 PG 11 WC Neurosciences SC Neurosciences & Neurology GA CY5QW UT WOS:000366463300024 PM 25787833 ER PT J AU Manian, FA AF Manian, Farrin A. TI End-Stage Kidney Disease: The Author Reply SO HEALTH AFFAIRS LA English DT Letter C1 [Manian, Farrin A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Manian, FA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV PY 2015 VL 34 IS 11 DI 10.1377/hlthaff.2015.1228 PG 1 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA CY9JU UT WOS:000366724000044 PM 26526270 ER PT J AU Allegra, CJ Yothers, G O'Connell, MJ Beart, RW Wozniak, TF Pitot, HC Shields, AF Landry, JC Ryan, DP Arora, A Evans, LS Bahary, N Soori, G Eakle, JF Robertson, JM Moore, DF Mullane, MR Marchello, BT Ward, PJ Sharif, S Roh, MS Wolmark, N AF Allegra, Carmen J. Yothers, Greg O'Connell, Michael J. Beart, Robert W. Wozniak, Timothy F. Pitot, Henry C. Shields, Anthony F. Landry, Jerome C. Ryan, David P. Arora, Amit Evans, Lisa S. Bahary, Nathan Soori, Gamini Eakle, Janice F. Robertson, John M. Moore, Dennis F., Jr. Mullane, Michael R. Marchello, Benjamin T. Ward, Patrick J. Sharif, Saima Roh, Mark S. Wolmark, Norman TI Neoadjuvant 5-FU or Capecitabine Plus Radiation With or Without Oxaliplatin in Rectal Cancer Patients: A Phase III Randomized Clinical Trial SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID METASTATIC COLORECTAL-CANCER; ORAL CAPECITABINE; COLON-CANCER; PREOPERATIVE CHEMORADIOTHERAPY; ADJUVANT THERAPY; DOSE LEUCOVORIN; FLUOROURACIL; 5-FLUOROURACIL; CHEMOTHERAPY; INFUSION AB Background: National Surgical Adjuvant Breast and Bowel Project R-04 was designed to determine whether the oral fluoropyrimidine capecitabine could be substituted for continuous infusion 5-FU in the curative setting of stage II/III rectal cancer during neoadjuvant radiation therapy and whether the addition of oxaliplatin could further enhance the activity of fluoropyrimidine-sensitized radiation. Methods: Patients with clinical stage II or III rectal cancer undergoing preoperative radiation were randomly assigned to one of four chemotherapy regimens in a 2x2 design: CVI 5-FU or oral capecitabine with or without oxaliplatin. The primary endpoint was local-regional tumor control. Time-to-event endpoint distributions were estimated using the Kaplan-Meier method. Hazard ratios were estimated from Cox proportional hazard models. All statistical tests were two-sided. Results: Among 1608 randomized patients there were no statistically significant differences between regimens using 5-FU vs capecitabine in three-year local-regional tumor event rates (11.2% vs 11.8%), 5-year DFS (66.4% vs 67.7%), or 5-year OS (79.9% vs 80.8%); or for oxaliplatin vs no oxaliplatin for the three endpoints of local-regional events, DFS, and OS (11.2% vs 12.1%, 69.2% vs 64.2%, and 81.3% vs 79.0%). The addition of oxaliplatin was associated with statistically significantly more overall and grade 3-4 diarrhea (P < .0001). Three-year rates of local-regional recurrence among patients who underwent R0 resection ranged from 3.1 to 5.1% depending on the study arm. Conclusions: Continuous infusion 5-FU produced outcomes for local-regional control, DFS, and OS similar to those obtained with oral capecitabine combined with radiation. This study establishes capecitabine as a standard of care in the pre-operative rectal setting. Oxaliplatin did not improve the local-regional failure rate, DFS, or OS for any patient risk group but did add considerable toxicity. C1 [Allegra, Carmen J.; Yothers, Greg; O'Connell, Michael J.; Beart, Robert W.; Wozniak, Timothy F.; Pitot, Henry C.; Shields, Anthony F.; Landry, Jerome C.; Ryan, David P.; Arora, Amit; Evans, Lisa S.; Bahary, Nathan; Soori, Gamini; Eakle, Janice F.; Robertson, John M.; Moore, Dennis F., Jr.; Mullane, Michael R.; Marchello, Benjamin T.; Ward, Patrick J.; Sharif, Saima; Roh, Mark S.; Wolmark, Norman] NRG Oncol Natl Surg Adjuvant Breast & Bowel Proje, Pittsburgh, PA USA. [Allegra, Carmen J.] Univ Florida Hlth, Dept Med, Gainesville, FL 32610 USA. [Yothers, Greg] NRG Oncol, Pittsburgh, PA USA. [Yothers, Greg] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. [Beart, Robert W.] Glendale Mem Hosp, Glendale, CA USA. [Wozniak, Timothy F.] CCOP Christiana Care Hlth Syst, Newark, DE USA. [Pitot, Henry C.] Mayo Clin, Rochester, MN USA. [Pitot, Henry C.; Ryan, David P.] ALLIANCE, Boston, MA USA. [Shields, Anthony F.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Shields, Anthony F.] SWOG, San Antonio, TX USA. [Landry, Jerome C.] Emory Univ, Dept Radiat Oncol, Atlanta, GA 30322 USA. [Landry, Jerome C.] ECOG ACRIN, Rochester, MN USA. [Ryan, David P.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Arora, Amit] Kaiser Permanente, Fremont, CA USA. [Evans, Lisa S.] Novant Hlth Forsyth Med Ctr, Winston Salem, NC USA. [Bahary, Nathan] Univ Pittsburgh, Pittsburgh, PA USA. [Soori, Gamini] Missouri Valley Canc Consortium CCOP, Omaha, NE USA. [Eakle, Janice F.] Florida Canc Specialists, Ft Myers, FL USA. [Robertson, John M.] Beaumont Hosp Syst, Royal Oak, MI USA. [Moore, Dennis F., Jr.] Canc Ctr Kansas, Wichita, KS USA. [Mullane, Michael R.] Stroger Hosp Chicago MU NCORP, Chicago, IL USA. [Marchello, Benjamin T.] Montana Canc Consortium, Billings, MT USA. [Ward, Patrick J.] Oncol & Hematol Care, Cincinnati, OH USA. [Roh, Mark S.] UF Hlth Canc Ctr, Orlando, FL USA. [Wolmark, Norman] Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA. RP Allegra, CJ (reprint author), Univ Florida Hlth, Dept Med, 1600 SW Archer Rd, Gainesville, FL 32610 USA. EM carmen.allegra@medicine.ufl.edu FU US National Cancer Institute at National Institutes of Health; US Department of Health and Human Services, Public Health Service grants [U10-CA180868, U10-CA180822, UG1-CA189867, U10-CA180888, U10-CA180820, U10-CA180821] FX This work was supported by the US National Cancer Institute at the National Institutes of Health, US Department of Health and Human Services, Public Health Service grants (grant numbers U10-CA180868, U10-CA180822, UG1-CA189867, U10-CA180888, U10-CA180820, and U10-CA180821). The National Surgical Adjuvant Breast and Bowel Project is now a member of NRG Oncology. NR 33 TC 7 Z9 7 U1 1 U2 4 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 NOV PY 2015 VL 107 IS 11 AR djv248 DI 10.1093/jnci/djv248 PG 8 WC Oncology SC Oncology GA CZ2YZ UT WOS:000366972300001 ER PT J AU Gupta, S Artomov, M Goggins, W Daly, M Tsao, H AF Gupta, Sameer Artomov, Mykyta Goggins, William Daly, Mark Tsao, Hensin TI Gender Disparity and Mutation Burden in Metastatic Melanoma SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CUTANEOUS MELANOMA; CELL-CARCINOMA; MEN; SEX AB Gender differences in melanoma incidence and outcome have been consistently observed but remain biologically unexplained. We hypothesized that tumors are genetically distinct between men and women and analyzed the mutation spectra in 266 metastatic melanomas (102 women and 164 men) from The Cancer Genome Atlas (TCGA). We found a statistically significantly greater burden of missense mutations among men (male median 298 vs female median = 211.5; male-to-female ratio [M:F] = 1.85, 95% confidence interval [CI] = 1.44 to 2.39). We validated these initial findings using available data from a separate melanoma exome cohort (n = 95) and found a similar increase in missense mutations among men (male median 393 vs female median 259; M: F = 1.59, 95% CI = 1.12 to 2.27). In addition, we found improved survival with increasing log-transformed missense mutation count (univariate hazard ratio = 0.82, 95% CI = 0.69 to 0.98) for TCGA samples. Our analyses demonstrate for the first time a gender difference in mutation burden in cutaneous melanoma. C1 [Gupta, Sameer; Tsao, Hensin] Harvard Univ, Sch Med, Dept Dermatol, Wellman Ctr Photomed,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Artomov, Mykyta; Daly, Mark] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Artomov, Mykyta; Daly, Mark] Broad Inst, Cambridge, MA USA. [Artomov, Mykyta] Harvard Univ, Chem & Chem Biol Dept, Cambridge, MA 02138 USA. [Goggins, William] Chinese Univ Hong Kong, Sch Publ Hlth & Primary Care, Hong Kong, Hong Kong, Peoples R China. RP Tsao, H (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Wellman Ctr Photomed,Massachusetts Gen Hosp, Boston, MA 02115 USA. EM htsao@partners.org FU National Institutes of Health [K24 CA149202]; Melanoma Research Foundation FX This work was supported by the National Institutes of Health (K24 CA149202 to HT), the Melanoma Research Foundation (Medical Student Award to SG), and the generous donors to the Massachusetts General Hospital on behalf of melanoma research. NR 16 TC 2 Z9 2 U1 1 U2 1 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 NOV PY 2015 VL 107 IS 11 AR djv221 DI 10.1093/jnci/djv221 PG 4 WC Oncology SC Oncology GA CZ2YZ UT WOS:000366972300012 ER PT J AU Hung, RJ Ulrich, CM Goode, EL Brhane, Y Muir, K Chan, AT Le Marchand, L Schildkraut, J Witte, JS Eeles, R Boffetta, P Spitz, MR Poirier, JG Rider, DN Fridley, BL Chen, ZH Haiman, C Schumacher, F Easton, DF Landi, MT Brennan, P Houlston, R Christiani, DC Field, JK Bickeboller, H Risch, A Kote-Jarai, Z Wiklund, F Gronberg, H Chanock, S Berndt, SI Kraft, P Lindstrom, S Al Olama, AA Song, HL Phelan, C Wentzensen, N Peters, U Slattery, ML Sellers, TA Casey, G Gruber, SB Hunter, DJ Amos, CI Henderson, B AF Hung, Rayjean J. Ulrich, Cornelia M. Goode, Ellen L. Brhane, Yonathan Muir, Kenneth Chan, Andrew T. Le Marchand, Loic Schildkraut, Joellen Witte, John S. Eeles, Rosalind Boffetta, Paolo Spitz, Margaret R. Poirier, Julia G. Rider, David N. Fridley, Brooke L. Chen, Zhihua Haiman, Christopher Schumacher, Fredrick Easton, Douglas F. Landi, Maria Teresa Brennan, Paul Houlston, Richard Christiani, David C. Field, John K. Bickeboeller, Heike Risch, Angela Kote-Jarai, Zsofia Wiklund, Fredrik Gronberg, Henrik Chanock, Stephen Berndt, Sonja I. Kraft, Peter Lindstrom, Sara Al Olama, Ali Amin Song, Honglin Phelan, Catherine Wentzensen, Nicholas Peters, Ulrike Slattery, Martha L. Sellers, Thomas A. Casey, Graham Gruber, Stephen B. Hunter, David J. Amos, Christopher I. Henderson, Brian CA GECCO FOCI CORECT DRIVE GAME-ON Network TI Cross Cancer Genomic Investigation of Inflammation Pathway for Five Common Cancers: Lung, Ovary, Prostate, Breast, and Colorectal Cancer SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; TELOMERE DYSFUNCTION; GENOTYPE IMPUTATION; TERT-CLPTM1L LOCUS; SEQUENCE VARIANTS; GENETIC-VARIATION; INNATE IMMUNITY; IDENTIFIES 2; RISK LOCI AB Background: Inflammation has been hypothesized to increase the risk of cancer development as an initiator or promoter, yet no large-scale study of inherited variation across cancer sites has been conducted. Methods: We conducted a cross-cancer genomic analysis for the inflammation pathway based on 48 genome-wide association studies within the National Cancer Institute GAME-ON Network across five common cancer sites, with a total of 64 591 cancer patients and 74 467 control patients. Subset-based meta-analysis was used to account for possible disease heterogeneity, and hierarchical modeling was employed to estimate the effect of the subcomponents within the inflammation pathway. The network was visualized by enrichment map. All statistical tests were two-sided. Results: We identified three pleiotropic loci within the inflammation pathway, including one novel locus in Ch12q24 encoding SH2B3 (rs3184504), which reached GWAS significance with a P value of 1.78 x 10(-8), and it showed an association with lung cancer (P = 2.01 x 10(-6)), colorectal cancer (GECCO P = 6.72x10(-6); CORECT P = 3.32x10(-5)), and breast cancer (P = .009). We also identified five key subpathway components with genetic variants that are relevant for the risk of these five cancer sites: inflammatory response for colorectal cancer (P = .006), inflammation related cell cycle gene for lung cancer (P = 1.35x10(-6)), and activation of immune response for ovarian cancer (P = .009). In addition, sequence variations in immune system development played a role in breast cancer etiology (P = .001) and innate immune response was involved in the risk of both colorectal (P = .022) and ovarian cancer (P = .003). Conclusions: Genetic variations in inflammation and its related subpathway components are keys to the development of lung, colorectal, ovary, and breast cancer, including SH2B3, which is associated with lung, colorectal, and breast cancer. C1 [Hung, Rayjean J.; Brhane, Yonathan; Poirier, Julia G.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5T 3L9, Canada. [Ulrich, Cornelia M.; Risch, Angela] Natl Ctr Tumor Dis, Heidelberg, Germany. [Ulrich, Cornelia M.; Risch, Angela] German Canc Res Ctr, Heidelberg, Germany. [Goode, Ellen L.; Rider, David N.] Mayo Clin, Rochester, MN USA. [Muir, Kenneth] Univ Warwick, Coventry CV4 7AL, W Midlands, England. [Chan, Andrew T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA. [Schildkraut, Joellen] Duke Univ, Durham, NC USA. [Witte, John S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Eeles, Rosalind; Houlston, Richard; Kote-Jarai, Zsofia] Inst Canc Res, London SW3 6JB, England. [Boffetta, Paolo] Mt Sinai Sch Med, New York, NY USA. [Spitz, Margaret R.] Baylor Coll Med, Houston, TX 77030 USA. [Fridley, Brooke L.] Univ Kansas, Med Ctr, Dept Biostat, Kansas City, KS 66103 USA. [Chen, Zhihua; Phelan, Catherine; Sellers, Thomas A.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Haiman, Christopher; Schumacher, Fredrick; Casey, Graham; Gruber, Stephen B.; Henderson, Brian] Univ South Calif, Los Angeles, CA USA. [Easton, Douglas F.; Al Olama, Ali Amin; Song, Honglin] Univ Cambridge, Cambridge, England. [Landi, Maria Teresa; Chanock, Stephen; Berndt, Sonja I.; Wentzensen, Nicholas] NCI, Bethesda, MD 20892 USA. [Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France. [Christiani, David C.; Kraft, Peter; Lindstrom, Sara; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Field, John K.] Univ Liverpool, Liverpool L69 3BX, Merseyside, England. [Bickeboeller, Heike] Univ Gottingen, Sch Med, D-37073 Gottingen, Germany. [Wiklund, Fredrik; Gronberg, Henrik] Karolinska Inst, Stockholm, Sweden. [Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Ulrich, Cornelia M.; Slattery, Martha L.] Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA. [Ulrich, Cornelia M.; Slattery, Martha L.] Huntsman Canc Inst, Salt Lake City, UT USA. [Amos, Christopher I.] Dartmouth Coll, Geisel Sch Med, Lebanon, NH 03756 USA. RP Hung, RJ (reprint author), Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, 60 Murray St, Toronto, ON M5T 3L9, Canada. EM rayjean.hung@lunenfeld.ca RI Hung, Rayjean/A-7439-2013; Risch, Angela/H-2669-2013 OI Eeles, Rosalind/0000-0002-3698-6241; Risch, Angela/0000-0002-8026-5505 FU TRICL (Transdisciplinary Research for Cancer of Lung); International Lung Cancer Consortium (ILCCO): National Institute of Health [U19 CA148127-01]; Canadian Cancer Society Research Institute [020214]; DRIVE (Discovery, Biology, and Risk of Inherited Variants in Breast Cancer): National Institute of Health [U19 CA148065]; CORECT (ColoRectal Transdisciplinary Study): National Institute of Health [U19 CA148107, R01 CA81488, P30 CA014089]; GAME-ON U19 initiative for prostate cancer (ELLIPSE) [U19 CA148537]; FOCI (Transdisciplinary Cancer Genetic Association and Interacting Studies): National Institutes of Health [U19 CA148112-01, R01-CA122443, P50-CA136393, P30-CA15083]; Cancer Research UK [C490/A8339, C490/A16561, C490/A10119, C490/A10124]; GECCO (Genetics and Epidemiology of Colorectal Cancer Consortium): National Cancer Institute, National Institutes of Health, US Department of Health and Human Services [U01 CA137088, R01 CA059045]; ASTERISK: a Hospital Clinical Research Program (PHRC); Regional Council of Pays de la Loire; Groupement des Entreprises Francaises dans la Lutte contre le Cancer (GEFLUC); Association Anne de Bretagne Genetique; Ligue Regionale Contre le Cancer (LRCC); DACHS: German Research Council (Deutsche Forschungsgemeinschaft) [BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1]; German Federal Ministry of Education and Research [01KH0404, 01ER0814]; DALS: National Institutes of Health [R01 CA48998]; National Institutes of Health [P01 CA 055075, UM1 CA167552, R01 137178, R01 CA 151993, R01 CA137178, P01 CA 087969, R01 CA151993, P50 CA 127003, R01 CA042182, R01 CA076366, K05 CA154337]; OFCCR: National Institutes of Health [U01 CA074783]; Ontario Ministry of Research and Innovation; Division of Cancer Prevention, National Cancer Institute, NIH, DHHS; National Institutes of Health (NIH); Genes, Environment, and Health Initiative (GEI) [Z01 CP 010200]; NIH [U01 HG004446, GEI U01 HG 004438]; National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, HHSN271201100004C] FX TRICL (Transdisciplinary Research for Cancer of Lung) and International Lung Cancer Consortium (ILCCO): National Institute of Health U19 CA148127-01 (PI: Amos), Canadian Cancer Society Research Institute (no. 020214, PI: Hung).; DRIVE (Discovery, Biology, and Risk of Inherited Variants in Breast Cancer): National Institute of Health U19 CA148065.; CORECT (ColoRectal Transdisciplinary Study): National Institute of Health U19 CA148107; R01 CA81488, P30 CA014089.; ELLIPSE (ELLIPSE, Elucidating Loci in Prostate Cancer Susceptibility): This work was support by the GAME-ON U19 initiative for prostate cancer (ELLIPSE), U19 CA148537.; FOCI (Transdisciplinary Cancer Genetic Association and Interacting Studies): National Institutes of Health U19 CA148112-01 (PI: Sellers), R01-CA122443, P50-CA136393, P30-CA15083 (PI: Goode), Cancer Research UK (C490/A8339, C490/A16561, C490/A10119, C490/A10124 [PI: Pharoah]).; GECCO (Genetics and Epidemiology of Colorectal Cancer Consortium): National Cancer Institute, National Institutes of Health, US Department of Health and Human Services (U01 CA137088; R01 CA059045). ASTERISK: a Hospital Clinical Research Program (PHRC) and supported by the Regional Council of Pays de la Loire, the Groupement des Entreprises Francaises dans la Lutte contre le Cancer (GEFLUC), the Association Anne de Bretagne Genetique and the Ligue Regionale Contre le Cancer (LRCC). DACHS: German Research Council (Deutsche Forschungsgemeinschaft, BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, and CH 117/1-1), and the German Federal Ministry of Education and Research (01KH0404 and 01ER0814). DALS: National Institutes of Health (R01 CA48998 to MLS); HPFS is supported by the National Institutes of Health (P01 CA 055075, UM1 CA167552, R01 137178, R01 CA 151993, and P50 CA 127003), NHS by the National Institutes of Health (R01 CA137178, P01 CA 087969, R01 CA151993, and P50 CA 127003), and PHS by the National Institutes of Health (R01 CA042182). OFCCR: National Institutes of Health, through funding allocated to the Ontario Registry for Studies of Familial Colorectal Cancer (U01 CA074783); see CFR section. Additional funding toward genetic analyses of OFCCR includes the Ontario Research Fund, the Canadian Institutes of Health Research, and the Ontario Institute for Cancer Research, through generous support from the Ontario Ministry of Research and Innovation. PLCO: Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. Additionally, a subset of control samples were genotyped as part of the Cancer Genetic Markers of Susceptibility (CGEMS) Prostate Cancer GWAS (Yeager M, et al. Nat Genet. 2007;39(5):645-649), Colon CGEMS pancreatic cancer scan (PanScan) (Amundadottir L, et al. Nat Genet. 2009;41(9):986-990 and Petersen GM, et al. Nat Genet. 2010;42(3):224-228), and the Lung Cancer and Smoking study. The prostate and PanScan study datasets were accessed with appropriate approval through the dbGaP online resource (http://cgems.cancer.gov/data/) accession numbers phs000207.v1.p1 and phs000206.v3.p2, respectively, and the lung datasets were accessed from the dbGaP website (http://www.ncbi.nlm.nih.gov/gap) through accession number phs000093.v2.p2. Funding for the Lung Cancer and Smoking study was provided by National Institutes of Health (NIH), Genes, Environment, and Health Initiative (GEI) Z01 CP 010200, NIH U01 HG004446, and NIH GEI U01 HG 004438. For the lung study, the GENEVA Coordinating Center provided assistance with genotype cleaning and general study coordination, and the Johns Hopkins University Center for Inherited Disease Research conducted genotyping. PMH: National Institutes of Health (R01 CA076366 to PA Newcomb). VITAL: National Institutes of Health (K05 CA154337). WHI: The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. NR 90 TC 5 Z9 6 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD NOV PY 2015 VL 107 IS 11 AR djv246 DI 10.1093/jnci/djv246 PG 10 WC Oncology SC Oncology GA CZ2YZ UT WOS:000366972300014 ER PT J AU Han, BK Rigsby, CK Hlavacek, A Leipsic, J Nicol, ED Siegel, MJ Bardo, D Abbara, S Ghoshhajra, B Lesser, JR Raman, S Crean, AM AF Han, B. Kelly Rigsby, Cynthia K. Hlavacek, Anthony Leipsic, Jonathon Nicol, Edward D. Siegel, Marilyn J. Bardo, Dianna Abbara, Suhny Ghoshhajra, Brian Lesser, John R. Raman, Subha Crean, Andrew M. TI Computed Tomography Imaging in Patients with Congenital Heart Disease Part I: Rationale and Utility. An Expert Consensus Document of the Society of Cardiovascular Computed Tomography (SCCT) SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY LA English DT Article DE Computed tomography imaging; Congenital heart disease ID DUAL-SOURCE CT; ARTERIAL SWITCH OPERATION; PULMONARY VENOUS CONNECTION; CARDIAC MAGNETIC-RESONANCE; MULTIDETECTOR-ROW CT; VENTRICULAR SEPTAL-DEFECT; OUTFLOW TRACT OBSTRUCTION; RIGHT CORONARY-ARTERY; SURGICALLY REPAIRED TETRALOGY; SINGLE-CENTER EXPERIENCE AB This is an expert consensus document created to provide information about the current use of cardiovascular computed tomography (CT) in patients of all ages with proven or suspected congenital heart disease (CHD). The discussion and recommendations are based on available literature and the judgment of a diverse group of subspecialists with extensive experience in the use of CT imaging in CHD. The field of CHD CT imaging is evolving rapidly with the availability of new scanner technology. In addition, the prevalence of palliated CHD has increased with marked improvements in patient survival. We believe it is important to review the clinical indications, strengths, limitations, and risks of cardiovascular CT in this patient population. This is the first of two complementary documents. It will concentrate on the disease entities and circumstances in which CT may be used. The second document will focus on recommendations for the technical performance of cardiovascular CT in patients with CHD. Successful cardiovascular CT imaging of CHD requires an in depth understanding of the core teaching elements of both cardiology and radiology. The ability to perform and interpret high quality congenital cardiovascular CT in a clinical context requires focused time and effort regardless of the previous background of the cardiac imager. This is reflected by a writing committee that consists of pediatric and adult radiologists and cardiologists, all whom have extensive experience in performing CT in this patient population. Cardiovascular CT is complementary to other imaging modalities and its optimal use will be in centers where all diagnostic modalities are available. The choice of modality for an individual patient should be determined by age, diagnosis, clinical condition, clinical question and patient preference.(1-4) Use of CT in CHD should be reserved for situations in which it is expected to provide unique diagnostic information for the individual patient or clinical indication, and/or less risk than other modalities. This multi-disciplinary document is intended to guide the optimal selection of CHD patients for cardiovascular CT. The goals of this document apply to both pediatric and adult CHD patients and are to: 1) Review the current use of cardiovascular CT. 2) Assess the most up to date information on risks, benefits, as well as limitations of cardiovascular CT. 3) Provide disease-specific indications for cardiovascular CT imaging. 4) Outline a consensus opinion on the essential skills and knowledge needed to optimally perform and interpret cardiovascular CT. (C) 2015 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved. C1 [Han, B. Kelly] Childrens Hosp & Clin Minnesota, Childrens Heart Clin, Minneapolis Heart Inst, Minneapolis, MN 55454 USA. [Rigsby, Cynthia K.] Northwestern Univ Feinberg, Sch Med, Chicago, IL USA. [Rigsby, Cynthia K.] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. [Hlavacek, Anthony] Med Univ S Carolina, Charleston, SC 29425 USA. [Leipsic, Jonathon] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Nicol, Edward D.] Royal Brompton Hosp, London SW3 6LY, England. [Siegel, Marilyn J.] Washington Univ, Sch Med, St Louis, MO USA. [Bardo, Dianna] Phoenix Childrens Hosp, Phoenix, AZ USA. [Abbara, Suhny] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Ghoshhajra, Brian] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lesser, John R.] Minneapolis Heart Inst, Minneapolis, MN USA. [Raman, Subha] Ohio State Univ, Columbus, OH 43210 USA. [Crean, Andrew M.] Toronto Gen Hosp, Toronto, ON, Canada. RP Han, BK (reprint author), Childrens Hosp & Clin Minnesota, Childrens Heart Clin, Minneapolis Heart Inst, Minneapolis, MN 55454 USA. EM khan@chc-pa.org OI Hlavacek, Anthony/0000-0002-8281-1522 NR 395 TC 3 Z9 3 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-5925 J9 J CARDIOVASC COMPUT JI J. Cardiovasc. Comput. Tomogr. PD NOV-DEC PY 2015 VL 9 IS 6 BP 475 EP 492 DI 10.1016/j.jcct.2015.07.004 PG 18 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CZ2RJ UT WOS:000366952000001 PM 26272851 ER PT J AU Han, BK Rigsby, CK Leipsic, J Bardo, D Abbara, S Ghoshhajra, B Lesser, JR Raman, SV Crean, AM Nicol, ED Siegel, MJ Hlavacek, A AF Han, B. Kelly Rigsby, Cynthia K. Leipsic, Jonathon Bardo, Dianna Abbara, Suhny Ghoshhajra, Brian Lesser, John R. Raman, Subha V. Crean, Andrew M. Nicol, Edward D. Siegel, Marilyn J. Hlavacek, Anthony TI Computed Tomography Imaging in Patients with Congenital Heart Disease, Part 2: Technical Recommendations. An Expert Consensus Document of the Society of Cardiovascular Computed Tomography (SCCT) SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY LA English DT Article ID CORONARY CT ANGIOGRAPHY; DUAL-SOURCE CT; CARDIAC MAGNETIC-RESONANCE; LEFT-VENTRICULAR FUNCTION; KILOVOLTAGE SELECTION; REPAIRED TETRALOGY; FONTAN OPERATION; CONTRAST-MEDIUM; PEDIATRIC CT; 256-SLICE CT C1 [Han, B. Kelly] Childrens Hosp & Clin Minnesota, Childrens Heart Clin, Minneapolis Heart Inst, Minneapolis, MN 55454 USA. [Rigsby, Cynthia K.] Northwestern Univ Feinberg, Sch Med, Chicago, IL USA. [Rigsby, Cynthia K.] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA. [Leipsic, Jonathon] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Bardo, Dianna] Phoenix Childrens Hosp, Phoenix, AZ USA. [Abbara, Suhny] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Ghoshhajra, Brian] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lesser, John R.] Minneapolis Heart Inst, Minneapolis, MN USA. [Raman, Subha V.] Ohio State Univ, Columbus, OH 43210 USA. [Crean, Andrew M.] Toronto Gen Hosp, Toronto, ON, Canada. [Nicol, Edward D.] Royal Brompton Hosp, London SW3 6LY, England. [Siegel, Marilyn J.] Washington Univ, Sch Med, St Louis, MO USA. [Hlavacek, Anthony] Med Univ S Carolina, Charleston, SC 29425 USA. RP Han, BK (reprint author), Childrens Hosp & Clin Minnesota, Childrens Heart Clin, Minneapolis Heart Inst, Minneapolis, MN 55454 USA. EM khan@chc-pa.org OI Hlavacek, Anthony/0000-0002-8281-1522 NR 97 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-5925 J9 J CARDIOVASC COMPUT JI J. Cardiovasc. Comput. Tomogr. PD NOV-DEC PY 2015 VL 9 IS 6 BP 493 EP 513 DI 10.1016/j.jcct.2015.07.007 PG 21 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CZ2RJ UT WOS:000366952000002 PM 26679548 ER PT J AU Ferencik, M Mayrhofer, T Puchner, SB Lu, MT Maurovich-Horvat, P Liu, T Ghemigian, K Kitslaar, P Broersen, A Bamberg, F Truong, QA Schlett, CL Hoffmann, U AF Ferencik, Maros Mayrhofer, Thomas Puchner, Stefan B. Lu, Michael T. Maurovich-Horvat, Pal Liu, Ting Ghemigian, Khristine Kitslaar, Pieter Broersen, Alexander Bamberg, Fabian Truong, Quynh A. Schlett, Christopher L. Hoffmann, Udo TI Computed tomography-based high-risk coronary plaque score to predict acute coronary syndrome among patients with acute chest pain - Results from the ROMICAT II trial SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY LA English DT Article DE Coronary computed tomography angiography; Acute coronary syndrome; Coronary atherosclerotic plaque; Acute chest pain; Risk score ID ELEVATION MYOCARDIAL-INFARCTION; DUAL-SOURCE CT; INTRAVASCULAR ULTRASOUND; NONINVASIVE ASSESSMENT; VIRTUAL HISTOLOGY; CULPRIT LESIONS; ARTERY-DISEASE; DIAGNOSTIC PERFORMANCE; ATHEROSCLEROTIC PLAQUE; ANGIOGRAPHY AB Background: Coronary computed tomography angiography (CTA) can be used to detect and quantitatively assess high-risk plaque features. Objective: To validate the ROMICAT score, which was derived using semi-automated quantitative measurements of high-risk plaque features, for the prediction of ACS. Material and methods: We performed quantitative plaque analysis in 260 patients who presented to the emergency department with suspected ACS in the ROMICAT II trial. The readers used a semi-automated software (QAngio, Medis medical imaging systems BV) to measure high-risk plaque features (volume of <60HU plaque, remodeling index, spotty calcium, plaque length) and diameter stenosis in all plaques. We calculated a ROMICAT score, which was derived from the ROMICAT I study and applied to the ROMICAT II trial. The primary outcome of the study was diagnosis of an ACS during the index hospitalization. Results: Patient characteristics (age 57 +/- 8 vs. 56 +/- 8 years, cardiovascular risk factors) were not different between those with and without ACS (prevalence of ACS 7.8%). There were more men in the ACS group (84% vs. 59%, p = 0.005). When applying the ROMICAT score derived from the ROMICAT I trial to the patient population of the ROMICAT II trial, the ROMICAT score (OR 2.9, 95% Cl 1.4-6.0, p = 0.003) was a predictor of ACS after adjusting for gender and >= 50% stenosis. The AUC of the model containing ROMICAT score, gender, and >= 50% stenosis was 0.91 (95% CI 0.86-0.96) and was better than with a model that included only gender and >= 50% stenosis (AUC 0.85, 95%CI 0.77-0.92; p = 0.002). Conclusions: The ROMICAT score derived from semi-automated quantitative measurements of high-risk plaque features was an independent predictor of ACS during the index hospitalization and was incremental to gender and presence of >50% stenosis. (C) 2015 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved. C1 [Ferencik, Maros] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Portland, OR 97239 USA. [Ferencik, Maros; Mayrhofer, Thomas; Puchner, Stefan B.; Lu, Michael T.; Liu, Ting; Ghemigian, Khristine; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Ferencik, Maros; Mayrhofer, Thomas; Puchner, Stefan B.; Lu, Michael T.; Liu, Ting; Ghemigian, Khristine; Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA USA. [Ferencik, Maros; Mayrhofer, Thomas; Puchner, Stefan B.; Lu, Michael T.; Liu, Ting; Ghemigian, Khristine; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Puchner, Stefan B.] Med Univ Vienna, Dept Biomed Imaging & Image Guided Therapy, Vienna, Austria. [Maurovich-Horvat, Pal] Semmelweis Univ, Heart & Vasc Ctr, MTA SE Lendiilet Cardiovasc Imaging Res Grp, H-1085 Budapest, Hungary. [Liu, Ting] China Med Univ, Affiliated Hosp 1, Dept Radiol, Shenyang 110001, Peoples R China. [Kitslaar, Pieter; Broersen, Alexander] Leiden Univ, Med Ctr, Div Image Proc, Dept Radiol, Leiden, Netherlands. [Kitslaar, Pieter] Medis Med Imaging Syst BV, Leiden, Netherlands. [Bamberg, Fabian] Univ Tubingen, Dept Radiol, Tubingen, Germany. [Truong, Quynh A.] New York Presbyterian Hosp, Dalio Inst Cardiovasc Imaging, New York, NY USA. [Truong, Quynh A.] Weill Cornell Med Coll, New York, NY USA. [Schlett, Christopher L.] Univ Heidelberg Hosp, Diagnost & Intervent Radiol, Heidelberg, Germany. RP Ferencik, M (reprint author), Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, 3180 SW Sam Jackson Pk Rd,Mail Code UHN62, Portland, OR 97239 USA. EM ferencik@ohsu.edu FU National Heart, Lung, and Blood Institute [U01HL092040, U01HL092022]; American Heart Association [13FTF16450001]; NIH [U01HL092040, U01HL092022]; Siemens Medical Solutions; Heart Flow Inc.; NIH/NHLBI [K23HL098370, L30HL093896]; St. Jude Medical; American College of Radiology Imaging Network; Duke Clinical Research Institute FX This work was supported by grants from the National Heart, Lung, and Blood Institute (U01HL092040 and U01HL092022). Dr. Ferencik received support from the American Heart Association (13FTF16450001). Dr. Hoffmann received research grant support from NIH (U01HL092040, U01HL092022), Siemens Medical Solutions and Heart Flow Inc. and consultant/advisory board support from Heart Flow Inc. Pieter Kitslaar is an employee of Medis medical imaging systems B.V. Dr. Truong received support from the NIH/NHLBI K23HL098370 and L30HL093896, St. Jude Medical, American College of Radiology Imaging Network, and Duke Clinical Research Institute. NR 46 TC 7 Z9 7 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-5925 J9 J CARDIOVASC COMPUT JI J. Cardiovasc. Comput. Tomogr. PD NOV-DEC PY 2015 VL 9 IS 6 BP 538 EP 545 DI 10.1016/j.jcct.2015.07.003 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA CZ2RJ UT WOS:000366952000006 PM 26229036 ER PT J AU Lee, SY Gertler, FB Goldberg, MB AF Lee, Soo Young Gertler, Frank B. Goldberg, Marcia B. TI Vasodilator-stimulated phosphoprotein restricts cell-to-cell spread of Shigella flexneri at the cell periphery SO MICROBIOLOGY-SGM LA English DT Article ID ACTIN-BASED MOTILITY; PROTEIN-KINASE PHOSPHORYLATION; LISTERIA-MONOCYTOGENES; ENA/VASP PROTEINS; EPITHELIAL-CELLS; ARP2/3 COMPLEX; BURKHOLDERIA-PSEUDOMALLEI; RICKETTSIA-CONORII; BARBED END; IN-VITRO AB Shigella spp. are intracellular bacterial pathogens that cause diarrhoeal disease in humans. Shigella utilize the host actin cytoskeleton to enter cells, move through the cytoplasm of cells and pass into adjacent cells. Ena/VASP family proteins are highly conserved proteins that participate in actin-dependent dynamic cellular processes. We tested whether Ena/VASP family members VASP (vasodilator-stimulated phosphoprotein), Mena (mammalian-enabled) or EVL (Ena-VASP-like) contribute to Shigella flexneri spread through cell monolayers. VASP and EVL restricted cell-to-cell spread without significantly altering actin-based motility, whereas Mena had no effect on these processes. Phosphorylation of VASP on Ser153, Ser235 and Thr274 regulated its subcellular distribution and function. VASP derivatives that lack the Ena/VASP homology 1 (EVH1) domain or contain a phosphoablative mutation of Ser153 were defective in restricting S. flexneri spread, indicating that the EVH1 domain and phosphorylation on Ser153 are required for this process. The EVH1 domain and Ser153 of VASP were required for VASP localization to focal adhesions, and localization of VASP to focal adhesions and/or the leading edge was required for restriction of spread. The contribution of the EVH1 domain was from both the donor and the recipient cell, whereas the contribution of Ser153 phosphorylation was only from the donor cell. Thus, unlike host proteins characterized in Shigella pathogenesis that promote bacterial spread, VASP and EVL function to limit it. The ability of VASP and EVL to limit spread highlights the critical role of focal adhesion complexes and/or the leading edge in bacterial passage between cells. C1 [Lee, Soo Young; Goldberg, Marcia B.] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA. [Gertler, Frank B.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Goldberg, Marcia B.] Massachusetts Gen Hosp, Div Infect Dis, Cambridge, MA 02139 USA. RP Goldberg, MB (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02115 USA. EM marcia.goldberg@mgh.harvard.edu FU National Institutes of Health [R01AI081724, R21AI103676, R01GM58801]; Ludwig Center for Molecular Oncology at MIT FX This work was supported by the National Institutes of Health [R01AI081724 (to M. B. G.), R21AI103676 (to M. B. G.) and R01GM58801 (to F. B. G.)] and the Ludwig Center for Molecular Oncology at MIT (to F. B. G.). NR 56 TC 0 Z9 0 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD NOV PY 2015 VL 161 BP 2149 EP 2160 DI 10.1099/mic.0.000173 PN 11 PG 12 WC Microbiology SC Microbiology GA CZ6LP UT WOS:000367213100010 PM 26358985 ER PT J AU Chua, AS Glanz, BI Guarino, AJ Cook, SL Greeke, EE Little, GE Chitnis, T Healy, BC AF Chua, Alicia S. Glanz, Bonnie I. Guarino, Anthony J. Cook, Sandra L. Greeke, Emily E. Little, Grace E. Chitnis, Tanuja Healy, Brian C. TI Patient-reported outcomes in multiple sclerosis: Relationships among existing scales and the development of a brief measure SO MULTIPLE SCLEROSIS AND RELATED DISORDERS LA English DT Article DE Multiple sclerosis; Social support; Depression; Fatigue; Quality of life; Patient-reported outcomes ID QUALITY-OF-LIFE; PSYCHOMETRIC PROPERTIES; PROMIS DEPRESSION; HEALTH; QUESTIONNAIRE; DISABILITY; FATIGUE; INSTRUMENTS; CRITERIA; DISEASE AB Several patient-reported outcome (PRO) measures are commonly used in multiple sclerosis (MS) research, but the relationship among items across measures is uncertain. We proposed to evaluate the associations between items from a standard battery of PRO measures used in MS research and to develop a brief, reliable and valid instrument measure by combining these items into a single measure. Subjects (N=537) enrolled in CLIMB complete a PRO battery that includes the Center for Epidemiologic Studies Depression Scale, Medical Outcomes Study Modified Social Support Survey, Modified Fatigue Impact Scale and Multiple Sclerosis Quality of Life-54. Subjects were randomly divided into two samples: calibration (n=269) and validation (n=268). In the calibration sample, an Exploratory Factor Analysis (EFA) was used to identify latent constructs within the battery. The model constructed based on the EFA was evaluated in the validation sample using Confirmatory Factor Analysis (CFA), and reliability and validity were assessed for the final measure. The EFA in the calibration sample revealed an eight factor solution, and a final model with one second-order factor along with the eight first-order factors provided the best fit. The model combined items from each of the four parent measures, showing important relationships among the parent measures. When the model was fit using the validation sample, the results confirmed the validity and reliability of the model. A brief PRO for MS (BPRO-MS) that combines MS-related psychosocial and quality of life domains can be used to assess overall functioning in mildly disabled MS patients. (C) 2015 Elsevier B.V. All rights reserved. C1 [Chua, Alicia S.; Glanz, Bonnie I.; Cook, Sandra L.; Greeke, Emily E.; Little, Grace E.; Chitnis, Tanuja; Healy, Brian C.] Brigham & Womens Hosp, Partners Multiple Sclerosis Ctr, Boston, MA 02115 USA. [Glanz, Bonnie I.; Chitnis, Tanuja; Healy, Brian C.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Healy, Brian C.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Guarino, Anthony J.] Massachusetts Gen Hosp, Inst Hlth Profess, Ctr Intetprofess Studies & Innovat, Boston, MA 02114 USA. RP Healy, BC (reprint author), Partners MS Ctr, 1 Brookline Pl,Suite 602, Brookline, MA 02445 USA. EM bchealy@partners.org FU Nancy Davis Foundation; Merck Serono S.A. FX The CLIMB study is funded in part by the Nancy Davis Foundation and Merck Serono S.A. NR 38 TC 1 Z9 1 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2211-0348 EI 2211-0356 J9 MULT SCLER RELAT DIS JI Mult. Scler. Relat. Disord. PD NOV PY 2015 VL 4 IS 6 BP 598 EP 606 DI 10.1016/j.msard.2015.09.004 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA CZ2QL UT WOS:000366949600019 PM 26590669 ER PT J AU Chen, WL Wu, Y Shimizu, A Lian, YL Tasaki, M Villani, V Moran, S Xia, JJ Yamada, K Qi, ZQ AF Chen, WeiLi Wu, Yuan Shimizu, Akira Lian, YinLong Tasaki, Masayuki Villani, Vincenzo Moran, Shannon Xia, JunJie Yamada, Kazuhiko Qi, ZhongQuan TI Rat-to-Chinese tree shrew heart transplantation is a novel small animal model to study non-Gal-mediated discordant xenograft humoral rejection SO XENOTRANSPLANTATION LA English DT Article DE animal model; cardiac transplantation; Chinese tree shrews; xenograft rejection; xenotransplantation ID HUMAN NATURAL ANTIBODIES; CARDIAC XENOGRAFTS; ENDOTHELIAL-CELLS; NUCLEAR TRANSFER; KNOCKOUT PIGS; BONE-MARROW; BABOONS; ANTIGENS; ENGRAFTMENT; EXPRESSION AB Since -1,3-galactosyltransferase knockout (GalT-KO) pigs became available, there has been an increasing interest in non-Gal natural antibody (nAb)-mediated xenograft rejection. To better understand mechanisms of non-Gal nAb-mediated rejection, a simple small animal model without gene manipulation would be extremely valuable. Here, we tested whether the Chinese tree shrew (CTS), which is a small-sized mammal that is phylogenetically close to primates, could serve as a model for discordant xenograft rejection. MethodsStudy 1: Expression of -Gal antigens in hearts and kidneys of CTSs and rats was assessed by IB4 lectin binding. Presence of anti-Gal and anti-non-Gal IgM and IgG nAb in CTS sera was tested by FACS using Gal+ and GalTKO PBMC as well as BSA-ELISA. Study 2: Rat hearts were transplanted into CTS recipients (group 1, n = 7), and CTS hearts were transplanted in rats [n = 10; seven received no immunosuppression (group 2) and three received FK506 + leflunomide (group 3)]. ResultsStudy 1: Both CTSs and rats had -Gal expression in hearts and kidneys. ELISA showed CTSs do not have anti-Gal nAb, and flow cytometry indicated CTSs have anti-non-Gal IgM and IgG nAb in serum. Study 2: Rat hearts in CTSs were uniformly rejected within 35 mins, while CTS hearts in rats continued beating until day 5 without immunosuppression, and up to day 8 with immunosuppression. ConclusionRat-to-CTS heart transplantation is a discordant xenotransplant model, CTS-to-Rat heart transplantation is a concordant xenotransplant model. CTSs are valuable small animals to study mechanisms and strategies to avoid non-Gal nAb-mediated xenograft rejection. C1 [Chen, WeiLi; Wu, Yuan; Lian, YinLong; Xia, JunJie; Qi, ZhongQuan] Xiamen Univ, Organ Transplantat Inst, Xiamen, Fujian Province, Peoples R China. [Shimizu, Akira; Tasaki, Masayuki; Villani, Vincenzo; Moran, Shannon; Yamada, Kazuhiko] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. [Yamada, Kazuhiko] Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, New York, NY 10032 USA. [Yamada, Kazuhiko] Kagoshima Univ, Ctr Adv Biomed Sci & Swine Res, Organ Replacement & Xenotransplantat Surg, Kagoshima 890, Japan. RP Yamada, K (reprint author), Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, Surg Res, 650 W,168 St,BB1706E,168th St, New York, NY 10032 USA. EM ky2323@cumc.columbia.edu; oti@xmu.edu.cn RI Xia, Junjie/C-9726-2012 FU Kagoshima University; MGH Swine Facility grant [C06 RR020135673]; Major State Scientific Research Program of China [2012CBA01303]; National Natural Science Foundation of China [81441047, 31271038] FX The authors would like to thank Dr. Isabel Hanekamp for her helpful advice and review of this manuscript. We thank Dr. David H. Sachs to provide blood from MGH GalT-KO miniature swine. This research was supported by Kagoshima University research support funding (KY), the MGH Swine Facility grant C06 RR020135673 (DHS), the Major State Scientific Research Program of China 2012CBA01303 and the National Natural Science Foundation of China 81441047, 31271038 (ZQQ). NR 37 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0908-665X EI 1399-3089 J9 XENOTRANSPLANTATION JI Xenotransplantation PD NOV-DEC PY 2015 VL 22 IS 6 BP 468 EP 475 DI 10.1111/xen.12211 PG 8 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA CZ4GQ UT WOS:000367061900007 PM 26589781 ER PT J AU Xiang, M Nguyen, PL AF Xiang, Michael Nguyen, Paul L. TI Significant association of brachytherapy boost with reduced prostate cancer-specific mortality in contemporary patients with localized, unfavorable-risk prostate cancer SO BRACHYTHERAPY LA English DT Article DE Prostate cancer; Brachytherapy; Radiation therapy ID EXTERNAL-BEAM RADIATION; DOSE-RATE BRACHYTHERAPY; ANDROGEN-DEPRIVATION THERAPY; PERMANENT INTERSTITIAL BRACHYTHERAPY; RANDOMIZED CONTROLLED-TRIAL; BIOCHEMICAL FAILURE; ESCALATION TRIAL; RADIOTHERAPY; INTERMEDIATE; COMBINATION AB PURPOSE: A randomized trial recently found that adding brachytherapy (BT) boost to external beam radiation therapy (EBRT) improves biochemical recurrence-free survival but not prostate cancer-specific mortality (PCSM). We investigated the relationship between BT boost and PCSM in a modern cohort from a large population-based database. METHODS AND MATERIALS: We conducted an analysis of patients in Surveillance, Epidemiology, and End Results diagnosed with intermediate-or high-risk prostate cancer in 2004-2011, treated with EBRT only or EBRT + BT. The cumulative incidence of PCSM was evaluated in the presence of other-cause mortality as a competing risk. Propensity score matching and multivariable Fine and Gray proportional hazard models were used to evaluate the association of combined modality RT on PCSM. RESULTS: A total of 52,535 patients were identified, of which 19.6% were treated with EBRT + BT. One-third of cases were high-risk. On multivariable analysis, the adjusted hazard ratio (AHR) of PCSM for EBRT + BT vs. EBRT alone was 0.69 (95% confidence interval [CI], 0.55-0.87, p = 0.002), and the adjusted incidence of PCSM was 1.8% vs. 2.7% at 8 years, respectively. In subgroup analyses, the AHR for PCSM was also significantly reduced with EBRT + BT for high-risk disease (AHR 0.70; 95% CI, 0.52-0.94, p = 0.02; adjusted incidence of PCSM at 8 years, 5.4% vs. 7.6%), but not for intermediate-risk disease. CONCLUSIONS: BT boost was associated with a moderate reduction to PCSM in men with localized unfavorable-risk prostate cancer. Those most likely to benefit are younger patients with high-risk disease. (C) 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. C1 [Xiang, Michael; Nguyen, Paul L.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Xiang, M (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM michael.xiang@post.harvard.edu FU National Institute of General Medical Sciences [T32GM007753] FX This work was supported by award number T32GM007753 from the National Institute of General Medical Sciences. NR 34 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-4721 EI 1873-1449 J9 BRACHYTHERAPY JI Brachytherapy PD NOV-DEC PY 2015 VL 14 IS 6 BP 773 EP 780 DI 10.1016/j.brachy.2015.09.004 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CY6SV UT WOS:000366540000006 PM 26489921 ER PT J AU Raldow, AC Zhang, DJ Chen, MH Braccioforte, MH Moran, BJ D'Amico, AV AF Raldow, Ann C. Zhang, Danjie Chen, Ming-Hui Braccioforte, Michelle H. Moran, Brian J. D'Amico, Anthony V. TI Short-course androgen deprivation therapy and the risk of death from high-risk prostate cancer in men undergoing external beam radiation therapy and brachytherapy SO BRACHYTHERAPY LA English DT Article DE Prostate cancer; Androgen deprivation therapy; Brachytherapy; Survival ID COMPETING RISK; TRIAL; TERM; RADIOTHERAPY; FAILURE; AGE AB PURPOSE: We estimated the risks of prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) in men with high-risk prostate cancer (PC) undergoing external beam radiation therapy and brachytherapy with short-course androgen deprivation therapy (ADT) (median 4 months) as compared with men with more favorable-risk PC undergoing standard of care as per the National Comprehensive Cancer Network guidelines. METHODS AND MATERIALS: The prospective study cohort comprised 6595 consecutively treated men with T1-4 N0M0 PC whose treatment included brachytherapy between October 16, 1997, and May 28, 2013. Fine and Gray competing risk regression and Cox regression analyses were used to assess the risks of PCSM and ACM in men with high, unfavorable intermediate, and favorable intermediate risk as compared with low-risk PC. RESULTS: After median followup of 7.76 years, 820 men died (12.43%): 72 of PC (8.78%). Men with favorable intermediate-risk PC did not have significantly increased PCSM risk as compared with men with low-risk PC (adjusted hazard ratio [AHR], 1.26; 95% confidence interval [CI] 0.56, 2.88; p-Value 0.58), whereas men with high-risk PC (AHR, 3.74; 95% CI 1.12, 12.53; p-Value 0.032) and unfavorable intermediate-risk PC (AHR, 3.10; 95% CI 1.43, 6.72; p-Value 0.004) did. Based on 10-year adjusted point estimates of PCSM and ACM for men with high-risk PC being 6.01% (95% CI 3.79%, 8.94%) and 21.30% (95% CI 17.45%, 25.42%), respectively, PCSM comprised 28% of ACM. CONCLUSIONS: In the setting of external beam radiation therapy and brachytherapy, men with high-risk PC have low absolute adjusted estimates of PCSM (similar to 6%) during the first decade after treatment despite receiving only short-course ADT. Whether long-term ADT can lower PCSM and improve survival in these men requires additional study. (C) 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. C1 [Raldow, Ann C.] Harvard Radiat Oncol Program, Boston, MA USA. [Zhang, Danjie; Chen, Ming-Hui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. [Braccioforte, Michelle H.; Moran, Brian J.] Prostate Canc Fdn Chicago, Westmont, IL USA. [Raldow, Ann C.; D'Amico, Anthony V.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Raldow, AC (reprint author), Brigham & Womens Hosp, Harvard Radiat Oncol Program, 75 Francis St, Boston, MA 02115 USA. EM araldow@partners.org NR 30 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 1538-4721 EI 1873-1449 J9 BRACHYTHERAPY JI Brachytherapy PD NOV-DEC PY 2015 VL 14 IS 6 BP 781 EP 787 DI 10.1016/j.brachy.2015.08.004 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CY6SV UT WOS:000366540000007 PM 26361718 ER PT J AU Bair, RJ Bair, E Viswanathan, AN AF Bair, Ryan J. Bair, Eric Viswanathan, Akila N. TI A radiopaque polymer hydrogel used as a fiducial marker in gynecologic-cancer patients receiving brachytherapy SO BRACHYTHERAPY LA English DT Article DE Fiducial; Radiopaque polymer hydrogel; Brachytherapy ID CHRONIC HEPATITIS-C; PEGYLATED INTERFERONS; RADIATION-THERAPY; PLACEMENT; SPACER; COMPLICATIONS; VARIABILITY; PARAMETERS; TRACKING; SEALANT AB PURPOSE: We assessed a novel Food and Drug Administration approved hydrogel, synthesized as absorbable iodinated particles, in gynecologic-cancer patients undergoing computed tomography (CT) or magnetic resonance (MR) based brachytherapy after external beam radiation. METHODS AND MATERIALS: Nineteen patients underwent CT-guided (n = 13) or MR-Incguided (n = 6) brachytherapy for gynecologic cancers. Seventy-seven hydrogel injections were placed. The hydrogel material was injected into gross residual disease and/or key anatomic landmarks in amounts ranging from 0.1 to 0.4 mL. The visibility of the tracer was scored on CT and on MR images using a 5-point scoring scale. A Cohen's kappa statistic was calculated to assess interobserver agreement. To assess the unadjusted effects of baseline parameters on hydrogel visibility, we modeled visibility using a linear mixed-effect model. RESULTS: Injections were without complication. The kappa statistic was 0.77 (95% confidence interval [CI], 0.68-0.87). The volume of hydrogel injected was significantly associated with visibility on both CT (p = 0.032) and magnetic resonance imaging (p = 0.016). We analyzed visibility by location, controlling for amount. A 0.1-cc increase in volume injected was associated with increases of 0.54 (95% CI = 0.05-1.03) in the CT visibility score and 0.83 (95% CI = 0.17-1.49) in the MR visibility score. Injection of 0.4 cc or more was required for unequivocal visibility on CT or MR. No statistically significant correlation was found between tumor type, tumor location, or anatomical location of injection and visibility on either CT or magnetic resonance imaging. CONCLUSIONS: In this first report of an injectable radiopaque hydrogel, targets were visualized to assist with three-dimensional-based brachytherapy in gynecologic malignancies. This marker has potential for several applications, is easy to inject and visualize, and caused no acute complications. (C) 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. C1 [Bair, Ryan J.; Viswanathan, Akila N.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Bair, Ryan J.; Viswanathan, Akila N.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bair, Eric] Univ N Carolina, Dept Endodont, Chapel Hill, NC USA. [Bair, Eric] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. RP Viswanathan, AN (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, ASB1,L2,75 Francis St, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu FU NIH [R21 CA167800]; Boerner Family Fund FX Dr. A.N.V. receives support from the NIH R21 CA167800 (PI: Viswanathan) and the Boerner Family Fund. The TraceIT Tissue Marker was supplied by Augmenix, Inc., (Waltham, MA). NR 27 TC 0 Z9 0 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-4721 EI 1873-1449 J9 BRACHYTHERAPY JI Brachytherapy PD NOV-DEC PY 2015 VL 14 IS 6 BP 876 EP 880 DI 10.1016/j.brachy.2015.08.008 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA CY6SV UT WOS:000366540000018 PM 26481393 ER PT J AU Braunwald, E de Bold, AJ AF Braunwald, Eugene de Bold, A. J. TI Adolfo J. de Bold PhD OC FRSC: a pioneer in cardiovascular medicine SO EUROPEAN HEART JOURNAL LA English DT Editorial Material AB Eugene Braunwald MD discusses the discovery of the Natriuretic Peptide System by A J de Bold, which as a consequence, made it possible for the Federal Drug Administration to approve the first ARNi on 7 July 2015 C1 [Braunwald, Eugene] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. RP Braunwald, E (reprint author), Brigham & Womens Hosp, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD NOV 1 PY 2015 VL 36 IS 41 SI SI BP 2760 EP 2760 DI 10.1093/eurheartj/ehv445 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CY6AM UT WOS:000366489500004 PM 26224078 ER PT J AU Upadhyay, GA Singh, JP AF Upadhyay, Gaurav A. Singh, Jagmeet P. TI Cause of death and CRT device selection: striving for certitude? SO EUROPEAN HEART JOURNAL LA English DT Editorial Material ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; CARDIAC-RESYNCHRONIZATION THERAPY; HEART-FAILURE; EJECTION FRACTION; TRIAL; MORTALITY; SHOCKS; MODE C1 [Upadhyay, Gaurav A.] Univ Chicago Hosp, Heart Rhythm Ctr, Chicago, IL 60637 USA. [Singh, Jagmeet P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Singh, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv,Heart Ctr, Boston, MA 02114 USA. EM jsingh@mgh.harvard.edu NR 11 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD NOV 1 PY 2015 VL 36 IS 41 SI SI BP 2777 EP 2779 DI 10.1093/eurheartj/ehv474 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CY6AM UT WOS:000366489500009 PM 26374850 ER PT J AU Chatterjee, NA Roka, A Lubitz, SA Gold, MR Daubert, C Linde, C Steffel, J Singh, JP Mela, T AF Chatterjee, Neal A. Roka, Attila Lubitz, Steven A. Gold, Michael R. Daubert, Claude Linde, Cecilia Steffel, Jan Singh, Jagmeet P. Mela, Theofanie TI Reduced appropriate implantable cardioverter-defibrillator therapy after cardiac resynchronization therapy-induced left ventricular function recovery: a meta-analysis and systematic review SO EUROPEAN HEART JOURNAL LA English DT Article DE Resynchronization; Ventricular tachyarrhythmia; Meta-analysis ID CARE-HF TRIAL; HEART-FAILURE; EJECTION FRACTION; SUPER-RESPONDERS; ITALIAN REGISTRY; PREVENTION; ARRHYTHMIAS; SURVIVAL; REVERSE; DEATH AB Aims For patients undergoing cardiac resynchronization therapy (CRT) with implantable cardioverter-defibrillator (ICD; CRT-D), the effect of an improvement in left ventricular ejection fraction (LVEF) on appropriate ICD therapy may have significant implications regarding management at the time of ICD generator replacement. Methods and results We conducted a meta-analysis to determine the effect of LVEF recovery following CRT on the incidence of appropriate ICD therapy. A search of multiple electronic databases identified 709 reports, of which 6 retrospective cohort studies were included (n = 1740). In patients with post-CRT LVEF >= 35% (study n = 4), the pooled estimated rate of ICD therapy (5.5/100 person-years) was significantly lower than patients with post-CRT LVEF,35% [incidence rate difference (IRD): 26.5/100 person-years, 95% confidence interval (95% CI): 28.8 to 24.2, P < 0.001]. Similarly, patients with post-CRT LVEF = 45% (study n = 4) demonstrated lower estimated rates of ICD therapy (2.3/100 person-years) compared with patients without such recovery (IRD: 25.8/100 person-years, 95% CI: 27.6 to 24.0, P < 0.001). Restricting analysis to studies discounting ICD therapies during LVEF recovery (study n = 3), patients with LVEF recovery (= 35 or >= 45%) had significantly lower rates of ICD therapy compared with patients without such recovery (P for both,0.001). Patients with primary prevention indication for ICD, regardless of LVEF recovery definition, had very low rates of ICD therapy (0.4 to 0.8/100-person years). Conclusion Recovery of LVEF post-CRT is associated with significantly reduced appropriate ICD therapy. Patients with improvement of LVEF >= 45% and those with primary prevention indication for ICD appear to be at lowest risk. C1 [Chatterjee, Neal A.; Roka, Attila; Lubitz, Steven A.; Singh, Jagmeet P.; Mela, Theofanie] Massachusetts Gen Hosp, Ctr Heart, Dept Med, Boston, MA 02411 USA. [Chatterjee, Neal A.; Roka, Attila; Lubitz, Steven A.; Singh, Jagmeet P.; Mela, Theofanie] Massachusetts Gen Hosp, Ctr Heart, Cardiac Arrhythmia Serv, Boston, MA 02411 USA. [Gold, Michael R.] Med Univ S Carolina, Div Cardiol, Charleston, SC 29425 USA. [Daubert, Claude] Rennes Univ Hosp, Div Cardiol, Rennes, France. [Linde, Cecilia] Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden. [Steffel, Jan] Univ Zurich Hosp, Dept Cardiol, CH-8091 Zurich, Switzerland. RP Mela, T (reprint author), Massachusetts Gen Hosp, Ctr Heart, Dept Med, GRB 109,55 Fruit St, Boston, MA 02411 USA. EM tmela@mgh.harvard.edu FU NIH/NHLBI Career Development Award [K23HL114724]; Doris Duke Charitable Foundation Clinical Scientist Development Award [2014105]; Medtronic; Boston Scientific; St. Jude Medical; Swedish Heart Lung Foundation [20080498, 20110406]; Stockholm County Council [20090376, 20110610]; Cardio3; Novartis; Amgen; Astra-Zeneca; Atricure and Zoll Medical; Bayer; Biotronik; Biosense Webster; Boehringer-Ingelheim; Bristol-Myers Squibb; Daiichi-Sankyo; Cook Medical; Pfizer; Roche; Sanofi-Aventis; Sorin FX N.A.C. and A.R. report no disclosures. S.A.L. is supported by an NIH/NHLBI Career Development Award (K23HL114724) and a Doris Duke Charitable Foundation Clinical Scientist Development Award (2014105). M.R.G. is a consultant and receives lecture fees from Medtronic, Boston Scientific, and St. Jude Medical. C.D. receives speaker honoraria and consulting fees from Medtronic and St. Jude Medical. C.L. is supported by the Swedish Heart Lung Foundation [grants 20080498 and 20110406] and the Stockholm County Council [grants 20090376 and 20110610]. C.L. receives research grants, speaker honoraria, and consulting fees from Medtronic, speaker honoraria and consulting fees from St. Jude Medical, and consulting fees from Cardio3 and Novartis. J.S. has received consultant and/or speaker fees from Amgen, Astra-Zeneca, Atricure and Zoll Medical, Bayer, Biotronik, Biosense Webster, Boehringer-Ingelheim, Boston Scientific, Bristol-Myers Squibb, Daiichi-Sankyo, Cook Medical, Medtronic, Novartis, Pfizer, Roche, Sanofi-Aventis, Sorin and St. Jude Medical, and is co-director of CorXL LLC. He reports grant support through his institution from Bayer Healthcare, Biotronik, Daiichi Sankyo, Medtronic, and St. Jude Medical. J.P.S. is a consultant and receives lecture fees from Biotronik, Boston Scientific, Medtronic, Sorin Group, and St. Jude Medical, and is also a consultant for CardioInsight Inc, Thoratec Inc., and Biosense Webster. T.M. received speaker's honoraria from Medtronic, Biotronik, and Boston Scientific. NR 41 TC 9 Z9 10 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD NOV 1 PY 2015 VL 36 IS 41 SI SI BP 2780 EP 2789 DI 10.1093/eurheartj/ehv373 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CY6AM UT WOS:000366489500011 PM 26264552 ER PT J AU Teixeira, A Parenica, J Park, JJ Ishihara, S AlHabib, KF Laribi, S Maggioni, A Miro, O Sato, N Kajimoto, K Cohen-Solal, A Fairman, E Lassus, J Mueller, C Peacock, WF Januzzi, JL Choi, DJ Plaisance, P Spinar, J Mebazaa, A Gayat, E AF Teixeira, Antonio Parenica, Jiri Park, Jin Joo Ishihara, Shiro AlHabib, Khalid F. Laribi, Said Maggioni, Aldo Miro, Oscar Sato, Naoki Kajimoto, Katsuya Cohen-Solal, Alain Fairman, Enrique Lassus, Johan Mueller, Christian Peacock, William F. Januzzi, James L., Jr. Choi, Dong-Ju Plaisance, Patrick Spinar, Jindrich Mebazaa, Alexandre Gayat, Etienne CA GREAT Global Res Acute Conditions TI Clinical presentation and outcome by age categories in acute heart failure: results from an international observational cohort SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Heart failure; Heart failure with reduced ejection fraction; Elderly; Cardiac risk factors and prevention; Diabetes; Heart failure with preserved ejection fraction ID CONVERTING-ENZYME-INHIBITORS; ELDERLY-PATIENTS; OLDER-ADULTS; EMERGENCY-DEPARTMENT; EUROPEAN-SOCIETY; NATIONAL-SURVEY; PROTECT TRIAL; PREVALENCE; ASSOCIATION; MORTALITY AB Aims To assess, according to age groups, patients' characteristics according to region of origin, the chronic therapeutic management, prognostic utility of clinical variables, and natriuretic peptides. Methods and results The GREAT registry consisted of patients identified as presenting with acute heart failure at the emergency department. Four groups of patients were defined according to age: the young patient group (<65 years); 'middle-old' (65-74 years), 'old-old' (75-84 years) and the 'oldest-old' (85-94 years). Follow-up at 1 year was performed via personal contact or national data registries at 1 year. Dataset consisted of 14 758 patients aged up to 95 years, with the 'oldest-old' group being more prevalent in North America and Western Europe. The 30-day mortality rate were, respectively, 8.1%, 8.9%, 10.3%, and 16.3% among the four age groups and 1-year mortality rates were, respectively, 3.1%, 17.1%, 24.7%, and 39.9%. Chronic heart failure treatment was less frequently administered with age (percentage of the 'fully treated' group was 14% in the 'young' compared with 2% in the 'oldest-old' patient group). Reduced left ventricular ejection fraction was present in 70%, 62.3%, 52.5%, and 46.8% among the four age groups, respectively. The prognostic utility of most variables for short-and long-term outcome was attenuated with age, with the exception of natriuretic peptides. Conclusion This study found a large heterogeneity in age among geographic regions and that the eldest are less likely to be treated in accordance with recommendations of current heart failure guidelines. Natriuretic peptide concentrations retained prognostic value in patients across age strata. C1 [Teixeira, Antonio; Mebazaa, Alexandre] Hop Univ St Louis Lariboisiere, AP HP, Dept Geriatry, Paris, France. [Teixeira, Antonio; Laribi, Said; Cohen-Solal, Alain; Plaisance, Patrick; Mebazaa, Alexandre; Gayat, Etienne] Univ Paris Diderot, Paris, France. [Teixeira, Antonio; Ishihara, Shiro; Cohen-Solal, Alain; Plaisance, Patrick; Mebazaa, Alexandre; Gayat, Etienne] Univ Paris Diderot, Paris, France. [Teixeira, Antonio; Laribi, Said; Cohen-Solal, Alain; Mebazaa, Alexandre; Gayat, Etienne] INSERM, UMR S 942, Paris, France. [Parenica, Jiri; Spinar, Jindrich] Masaryk Univ, Fac Med, Brno, Czech Republic. [Park, Jin Joo; Choi, Dong-Ju] Seoul Natl Univ, Bundang Hosp, Dept Internal Med, Div Cardiol,Cardiovasc Ctr, Seoul 151, South Korea. [Ishihara, Shiro; Sato, Naoki] Nippon Med Sch, Musashi Kosugi Hosp, Tokyo, Japan. [AlHabib, Khalid F.] King Saud Univ, Coll Med, Dept Cardiac Sci, King Fahad Cardiac Ctr, Riyadh 11461, Saudi Arabia. [Laribi, Said; Plaisance, Patrick] Hop Univ St Louis Lariboisiere, AP HP, Emergency Dept, Paris, France. [Maggioni, Aldo] ANMCO Res Ctr, Florence, Italy. [Miro, Oscar] Hosp Clin Barcelona, Emergency Dept, Emergency Med Invest Grp Emergency Care Proc & Di, IDIBAPS, Barcelona, Spain. [Kajimoto, Katsuya] Towa Hosp, Div Cardiol, Tokyo, Japan. [Cohen-Solal, Alain] Hop Univ St Louis Lariboisiere, AP HP, Dept Cardiol, Paris, France. [Fairman, Enrique] Soc Argentina Cardiol, Area Invest SAC Azcuenaga, Buenos Aires, DF, Argentina. [Lassus, Johan] Univ Helsinki, Cent Hosp, Dept Med, Helsinki, Finland. [Mueller, Christian] Univ Basel Hosp, Dept Internal Med, CH-4031 Basel, Switzerland. [Peacock, William F.] Cleveland Clin, Emergency Med Inst, Cleveland, OH 44106 USA. [Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Gayat, Etienne] Hop Univ St Louis Lariboisiere, AP HP, Dept Anesthesiol & Crit Care Med, Paris, France. RP Gayat, E (reprint author), Hop Univ St Louis Lariboisiere Fernand Widal, AP HP, INSERM UMR S 942, Dept Anesthesiol & Intens Care Med, 2 Rue Ambroise Pare, F-75010 Paris, France. EM etienne.gayat@lrb.aphp.fr RI Laribi, said/S-3693-2016; OI Miro Andreu, Oscar/0000-0001-8127-166X FU Siemens; Singulex; Thermo Fisher; Novartis; Medicine Company; Bayer Health Care; Thermofisher; Orion-Pharma; Instituto de Salud Carlos III of Spanish Ministry of Health; FEDER [PI11/01021]; Catalonia Govern for Consolidated Groups of Investigation [GRC 2009/1385, 2014/0313]; Actelion; Ipsen; Sorin; Abbott; Alere; Pfizer; Vifor; Amgen; Servier; Bayer; Sanofi; Boehringer Ingelheim; Cardiorentis; Adrenomed; MyCartis; Critical Diagnostics FX Conflicts of interests: J.L.J. Jr reports receiving grants from Siemens, Singulex, and Thermo Fisher, and consulting income from Roche, Critical Diagnostics, Amgen, Novartis, and Sphingotec. O.M. received advisory/consulting fees from Novartis and The Medicine Company, research funding from Bayer Health Care, Thermofisher, Novartis, and Orion-Pharma, and was the recipient of Grants from Instituto de Salud Carlos III of Spanish Ministry of Health and FEDER (PI11/01021), and from the Catalonia Govern for Consolidated Groups of Investigation (GRC 2009/1385 and 2014/0313). A.C.S. received speaker and consulting fees from Actelion, Ipsen, Sorin, Abbott, Novartis, Thermofisher, Alere, Pfizer, Vifor, Amgen, Servier, Bayer, Sanofi, and Boehringer Ingelheim. A.M. received speaker's honoraria from The Medicines Company, Novartis, Orion, Roche, Servier, and Vifor Pharma, and received a fee as member of advisory board and/or Steering Committee from Cardiorentis, The Medicine Company, Adrenomed, MyCartis, and Critical Diagnostics. All other authors have no conflict of interest relevant to the contents of this paper. NR 35 TC 15 Z9 15 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD NOV PY 2015 VL 17 IS 11 BP 1114 EP 1123 DI 10.1002/ejhf.330 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CY4YP UT WOS:000366415100006 PM 26419908 ER PT J AU Cotter, G Voors, AA Prescott, MF Felker, GM Filippatos, G Greenberg, BH Pang, PS Ponikowski, P Milo, O Hua, TA Qian, M Severin, TM Teerlink, JR Metra, M Davison, BA AF Cotter, Gad Voors, Adriaan A. Prescott, Margaret F. Felker, G. Michael Filippatos, Gerasimos Greenberg, Barry H. Pang, Peter S. Ponikowski, Piotr Milo, Olga Hua, Tsushung A. Qian, Min Severin, Thomas M. Teerlink, John R. Metra, Marco Davison, Beth A. TI Growth differentiation factor 15 (GDF-15) in patients admitted for acute heart failure: results from the RELAX-AHF study SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Article DE Acute heart failure; GDF-15; RELAX-AHF study ID BETA SUPERFAMILY MEMBER; TROPONIN-T; INJURY; TRIAL AB Background Growth differentiation factor 15 (GDF-15) was found to be upregulated in patients with chronic heart failure (HF) and associated with disease severity, however, data on patients with acute heart failure (AHF) is lacking. Methods and results Levels of GDF-15 were measured at pre-specified time-points (baseline and at days 2, 5, 14, and 60) in patients enrolled in the placebo-controlled RELAXin in Acute Heart Failure (RELAX-AHF) study, which examined the effect of serelaxin in 1161 patients with AHF, systolic blood pressure >125 mmHg, and mild to moderate renal impairment. Neither baseline nor changes in GDF-15 were associated with the degree of dyspnoea or dyspnoea relief. After adjustment for baseline characteristics, baseline GDF-15 was not associated with the composite endpoint of heart failure or renal failure (HF/RF) readmission at 60 days/cardiovascular (CV) death or CV death at 180 days. In contrast, larger increases in GDF-15 levels at days 2 and 14 were associated with a greater risk of 60-day HF/RF rehospitalizations/CV death and CV death at 180 days. Serelaxin treatment was associated with significantly larger decreases of GDF-15 at days 2 and 5 than placebo. Conclusions In AHF patients enrolled in the RELAX-AHF study, increases in GDF-15 levels, but not baseline measurements, were associated with a greater likelihood of adverse outcomes. Serelaxin administration was associated with greater decreases in GDF-15 compared with placebo. C1 [Cotter, Gad; Milo, Olga; Davison, Beth A.] Momentum Res Inc, Durham, NC 27707 USA. [Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Prescott, Margaret F.; Hua, Tsushung A.; Severin, Thomas M.] Novartis Pharmaceut, New Hanover, NJ USA. [Felker, G. Michael] Duke Clin Res Inst, Durham, NC USA. [Filippatos, Gerasimos] Athens Univ Hosp, Athens, Greece. [Greenberg, Barry H.] Univ Calif San Diego, San Diego, CA 92103 USA. [Pang, Peter S.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [Ponikowski, Piotr] Med Univ, Clin Mil Hosp, Wroclaw, Poland. [Qian, Min] Columbia Univ, New York, NY USA. [Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. [Metra, Marco] Univ Brescia, Brescia, Italy. RP Cotter, G (reprint author), Momentum Res Inc, 3100 Tower Blvd, Durham, NC 27707 USA. EM gadcotter@momentum-research.com FU Novartis Pharmaceuticals Inc. FX This study was funded by Novartis Pharmaceuticals Inc. NR 17 TC 9 Z9 9 U1 2 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1388-9842 EI 1879-0844 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD NOV PY 2015 VL 17 IS 11 BP 1133 EP 1143 DI 10.1002/ejhf.331 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CY4YP UT WOS:000366415100008 PM 26333529 ER PT J AU Styer, AK Gaskins, AJ Brady, PC Sluss, PM Chavarro, JE Hauser, RB Toth, TL AF Styer, Aaron K. Gaskins, Audrey J. Brady, Paula C. Sluss, Patrick M. Chavarro, Jorge E. Hauser, Russ B. Toth, Thomas L. TI Dynamic antimullerian hormone levels during controlled ovarian hyperstimulation predict in vitro fertilization response and pregnancy outcomes SO FERTILITY AND STERILITY LA English DT Article DE Antimullerian hormone; assisted reproductive technology; controlled ovarian hyperstimulation; in vitro fertilization ID ANTI-MULLERIAN-HORMONE; ASSISTED REPRODUCTIVE TECHNOLOGY; INHIBIN-B; MENSTRUAL-CYCLE; LIVE-BIRTH; STIMULATED CYCLES; SPERM INJECTION; AGE WOMEN; ASSAYS; FSH AB Objective: To evaluate the patterns of change in serum antimullerian hormone (AMH) during controlled ovarian hyperstimulation (COH) and their relation to concurrent response and in vitro fertilization (IVF) pregnancy outcomes. Design: Prospective cohort study. Setting: Academic medical center. Patient(s): A total of 113 consecutive fresh IVF embryo transfer cycles from September 1, 2012 through January 1, 2013. Intervention(s): Serial serum AMH measurements were analyzed on each day that serum estradiol (E-2) was drawn during COH. Main Outcome Measure(s): Relationship between the rate of COH AMH change [Delta ng/mL per day] (stratified into tertiles), and ovarian response, and pregnancy outcomes. Result(s): During COH, AMH declined. Age and ovarian reserve testing were associated with the rate of AMH decline (RAD). Women with intermediate and minimal RAD had statistically significantly fewer follicles >= 12 mm, lower peak serum E-2, fewer oocytes, and inferior early embryo development compared with women with the greatest RAD. Compared with patients with the lowest RAD, clinical pregnancy was more likely in patients with the greatest RAD in the total population (adjusted odds ratio 3.51; 95% confidence interval, 1.03, 11.94) and among patients older than 35 years (adjusted odds ratio 6.95; 95% confidence interval, 1.09, 44.1). Conclusion(s): The rate of COH AMH decline was associated with ovarian reserve testing, oocyte yield, embryo progression, and clinical pregnancy rates, particularly in women older than 35 years. These results suggest that dynamic AMH levels may provide a novel intracycle approach to predict response and treatment outcomes after IVF. (C) 2015 by American Society for Reproductive Medicine. C1 [Styer, Aaron K.; Brady, Paula C.; Hauser, Russ B.; Toth, Thomas L.] Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Vincent Reprod Med & IVF, Boston, MA 02114 USA. [Styer, Aaron K.; Brady, Paula C.; Hauser, Russ B.; Toth, Thomas L.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Gaskins, Audrey J.; Chavarro, Jorge E.] Harvard Univ, Dept Nutr, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Sluss, Patrick M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Chavarro, Jorge E.; Hauser, Russ B.] Harvard Univ, Dept Epidemiol, TH Chan Sch Publ Hlth, Boston, MA USA. [Chavarro, Jorge E.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA. [Chavarro, Jorge E.] Harvard Univ, Harvard Med Sch, Boston, MA USA. [Hauser, Russ B.] Harvard Univ, Dept Environm Hlth, TH Chan Sch Publ Hlth, Boston, MA USA. RP Styer, AK (reprint author), Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Vincent Reprod Med & IVF, Yaw 10A,55 Fruit St, Boston, MA 02114 USA. EM astyer@mgh.harvard.edu OI Brady, Paula/0000-0002-2225-1148 FU National Institutes of Health FX A.K.S. has a patent pending. A.J.G. has nothing to disclose. P.C.B. has nothing to disclose. P.M.S. has a patent pending. J.E.C. has received a grant from the National Institutes of Health. R.B.H. has nothing to disclose. T.L.T. has a patent pending. NR 38 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD NOV PY 2015 VL 104 IS 5 BP 1153 EP + DI 10.1016/j.fertnstert.2015.07.1161 PG 16 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CY5ZK UT WOS:000366486400020 PM 26315051 ER PT J AU Vila, G Akerblad, AC Mattsson, AF Riedl, M Webb, SM Hana, V Nielsen, EH Biller, BMK Luger, A AF Vila, Greisa Akerblad, Ann-Charlotte Mattsson, Anders F. Riedl, Michaela Webb, Susan M. Hana, Vaclav Nielsen, Eigil H. Biller, Beverly M. K. Luger, Anton TI Pregnancy outcomes in women with growth hormone deficiency SO FERTILITY AND STERILITY LA English DT Article DE Growth hormone; hormone replacement therapy; pituitary deficiency; pituitary tumors; pregnancy ID DISEASE; SYSTEM; REPLACEMENT; ADULTS; GH AB Objective: To study pregnancies in a large group of patients with growth hormone deficiency and hypopituitarism; and to investigate potential factors determining pregnancy outcomes and pregnancy complications. Design: We analyzed pregnancies reported in KIMS, the Pfizer International Metabolic Database, of adult patients with growth hormone deficiency treated with growth hormone. Setting: Outpatient clinics. Patient(s): A total of 201 pregnancies were reported: 173 in female patients and 28 in partners of male patients. Intervention(s): Growth hormone replacement therapy (GHRT) was prescribed according to the local clinical practice. Main Outcome Measure(s): Pregnancy outcomes (live births, gestational week at delivery, and birth weight), pregnancy complications, and their relationship to use of GHRT during pregnancy were analyzed with regression models. Result(s): Two-thirds of women underwent fertility treatment to achieve pregnancy. Growth hormone replacement therapy was stopped before pregnancy in 7.5% of the female patients, as soon as pregnancy was confirmed in 40.1%, and at the end of the second trimester in 24.7% of the patients, whereas 27.6% continued GHRT throughout pregnancy. Birth of a healthy child was reported in 79% of the female pregnancies, nonelective abortions occurred mainly in the first trimester, and one fetal malformation (cystic hygroma) was diagnosed in the second trimester. Pregnancy outcomes and pregnancy complications were not related to GHRT treatment patterns, method of conception, or number of additional pituitary deficiencies. Conclusion(s): These data on pregnancy outcomes in a large group of women with hypopituitarism revealed no relationship between GHRT regimens and pregnancy outcomes. (C) 2015 by American Society for Reproductive Medicine. C1 [Vila, Greisa; Riedl, Michaela; Luger, Anton] Med Univ Vienna, Dept Internal Med 3, Div Endocrinol & Metab, Vienna, Austria. [Akerblad, Ann-Charlotte; Mattsson, Anders F.] Pfizer Endocrine Care, Sollentuna, Sweden. [Webb, Susan M.] Univ Autonoma Barcelona, Hosp St Pau, IIB St Pau, E-08193 Barcelona, Spain. [Webb, Susan M.] Univ Autonoma Barcelona, Hosp St Pau, Ctr Invest Biomed Enfermedades Raras CIBER ER, Dept Med,Unidad 747,Serv Endocrinol, E-08193 Barcelona, Spain. [Hana, Vaclav] Charles Univ Prague, Fac Med 1, Dept Internal Med 3, Prague, Czech Republic. [Nielsen, Eigil H.] Aalborg Univ Hosp, Dept Endocrinol, Aalborg, Denmark. [Biller, Beverly M. K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. RP Vila, G (reprint author), Med Univ Vienna, Dept Internal Med 3, Div Endocrinol & Metab, Vienna, Austria. EM greisa.vila@meduniwien.ac.at OI Webb, Susan/0000-0001-7052-6436; Vila, Greisa/0000-0003-1918-1959 FU Pfizer; OPKO FX G.V. is a speaker and receives occasional consulting honoraria from Pfizer and Novartis. A.-C. A. is a permanent employee at Pfizer Endocrine Care. A.F.M is a permanent employee at Pfizer Endocrine Care. M.R. receives speaker honoraria from Novo Nordisk. S.M.W. is a speaker and receives consulting honoraria from Pfizer. V.H. receives occasional consulting honoraria from Pfizer and speaker honoraria from Ipsen and Novartis. E.H.N. has nothing to disclose. B.M.K.B. receives occasional consulting honoraria from Pfizer, Versartis, and Novo Nordisk, and is principal investigator on a research grant to Massachusetts General Hospital from OPKO. A.L. is a speaker and receives consulting honoraria from Pfizer, Novo Nordisk, Ipsen, and Merck Serono.; KIMS is supported by Pfizer. NR 22 TC 3 Z9 3 U1 4 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD NOV PY 2015 VL 104 IS 5 BP 1210 EP + DI 10.1016/j.fertnstert.2015.07.1132 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA CY5ZK UT WOS:000366486400028 PM 26256649 ER PT J AU Maeng, LY Milad, MR AF Maeng, Lisa Y. Milad, Mohammed R. TI Sex differences in anxiety disorders: Interactions between fear, stress, and gonadal hormones SO HORMONES AND BEHAVIOR LA English DT Article DE Sex difference; Anxiety; Fear extinction; Fear conditioning; PTSD; Estrogen; Testosterone; Progesterone; Stress; Psychiatric disorders ID MEDIAL PREFRONTAL CORTEX; NATIONAL-COMORBIDITY-SURVEY; LONG-TERM POTENTIATION; ESTROGEN-RECEPTOR-BETA; PITUITARY-ADRENAL AXIS; CORTICOTROPIN-RELEASING-FACTOR; PROLONGED EXPOSURE THERAPY; GENDER-DIFFERENCES; MENSTRUAL-CYCLE; CONDITIONED FEAR AB This article is part of a Special Issue "SBN 2014". Women are more vulnerable to stress- and fear-based disorders, such as anxiety and post-traumatic stress disorder. Despite the growing literature on this topic, the neural basis of these sex differences remains unclear, and the findings appear inconsistent The neurobiological mechanisms of fear and stress in learning and memory processes have been extensively studied, and the crosstalk between these systems is beginning to explain the disproportionate incidence and differences in symptomatology and remission within these psychopathologies. In this review, we discuss the intersect between stress and fear mechanisms and their modulation by gonadal hormones and discuss the relevance of this information to sex differences in anxiety and fear-based disorders. Understanding these converging influences is imperative to the development of more effective, individualized treatments that take sex and hormones into account. Published by Elsevier Inc. C1 [Maeng, Lisa Y.; Milad, Mohammed R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. RP Milad, MR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, 149 13th St, Charlestown, MA 02129 USA. EM lmaeng@mgh.harvard.edu; milad@nmr.mgh.harvard.edu FU [1R01MH097880-001] FX We appreciate the helpful and thoughtful comments on this manuscript from the members of the Behavioral Neuroscience Program in the Department of Psychiatry at Massachusetts General Hospital. Special thanks to Dr. Marie-France Marin and Kara K. Cover for editorial assistance. MRM is supported by 1R01MH097880-001. NR 218 TC 13 Z9 13 U1 16 U2 35 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0018-506X EI 1095-6867 J9 HORM BEHAV JI Horm. Behav. PD NOV PY 2015 VL 76 SI SI BP 106 EP 117 DI 10.1016/j.yhbeh.2015.04.002 PG 12 WC Behavioral Sciences; Endocrinology & Metabolism SC Behavioral Sciences; Endocrinology & Metabolism GA CY6TC UT WOS:000366540700012 PM 25888456 ER PT J AU Batista, EK Klauss, J Fregni, F Nitsche, MA Nakamura-Palacios, EM AF Batista, Edson Kruger Klauss, Jaisa Fregni, Felipe Nitsche, Michael A. Nakamura-Palacios, Ester Miyuki TI A Randomized Placebo-Controlled Trial of Targeted Prefrontal Cortex Modulation with Bilateral tDCS in Patients with Crack-Cocaine Dependence SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Article DE tDCS; crack-cocaine; dorsolateral prefrontal cortex; craving; quality of life ID DIRECT-CURRENT STIMULATION; COMPULSIVE DRINKING SCALE; SELF-RATED INSTRUMENT; HUMAN MOTOR CORTEX; ALCOHOL DEPENDENCE; COGNITIVE CONTROL; DOUBLE-BLIND; WHOQOL-BREF; ADDICTION; NEUROBIOLOGY AB Background: Transcranial direct current stimulation over the dorsolateral prefrontal cortex has been shown to be clinically useful in the treatment of drug addiction. Methods: We conducted a double-blind randomized clinical trial aiming to assess the effects of bilateral dorsolateral prefrontal cortex transcranial direct current stimulation (left cathodal/right anodal) on crack-cocaine addiction. We defined craving as the primary outcome, and other clinical measurements, including depressive and anxiety symtoms, and quality of life, as secondary outcomes. Seventeen male crack-cocaine users (mean age 30.4 +/- 9.8 SD) were randomized to receive 5 sessions of active transcranial direct current stimulation (2 mA, 35 cm(2), for 20 minutes), every other day, and 19 males (mean age 30.3 +/- 8.4 SD) to receive sham-transcranial direct current stimulation (placebo) as control group. Results: Craving scores were significantly reduced in the transcranial direct current stimulation group after treatment when compared with sham-transcranial direct current stimulation (P =.028) and baseline values (P =.003), and decreased linearly over 4 weeks (before, during, and after treatment) in the transcranial direct current stimulation group only (P =.047). Changes of anxiety scores towards increase in the sham-transcranial direct current stimulation and decrease in the transcranial direct current stimulation group (P =.03), and of the overall perception of quality of life (P =.031) and of health (P =.048) towards decrease in the sham-transcranial direct current stimulation group and increase in the transcranial direct current stimulation group differed significantly between groups. Conclusions: Repetitive bilateral transcranial direct current stimulation over the dorsolateral prefrontal cortex reduced craving for crack-cocaine use, decreased anxiety, and improved quality of life. We hypothesize that transcranial direct current stimulation effects may be associated with increased prefrontal processing and regulation of craving behavior. C1 [Batista, Edson Kruger; Klauss, Jaisa; Nakamura-Palacios, Ester Miyuki] Univ Fed Espirito Santo, Program Post Grad Physiol Sci, Lab Cognit Sci & Neuropsychopharmacol, BR-29043900 Vitoria, ES, Brazil. [Fregni, Felipe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Spaulding Neuromodulat Ctr,Dept Phys Med & Rehabi, Boston, MA USA. [Fregni, Felipe] Harvard Univ, Sch Med, Dept Neurol, Berenson Allen Ctr Noninvas Brain Stimulat,Beth I, Boston, MA 02115 USA. [Nitsche, Michael A.] Univ Gottingen, Dept Clin Neurophysiol, Univ Med Ctr, Lab Neuroplast, D-37073 Gottingen, Germany. [Nitsche, Michael A.] Leibniz Res Ctr Working Environm & Human Resource, Dortmund, Germany. [Nitsche, Michael A.] Univ Med Hosp Bergmannsheil, Dept Neurol, Bochum, Germany. RP Nakamura-Palacios, EM (reprint author), Univ Fed Espirito Santo, Ctr Ciencias Saude, Programa Pos Grad Ciencias Fisiol, Ave Marechal Campos 1468, BR-29043900 Vitoria, ES, Brazil. EM emnpalacios@gmail.com FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [475232/2013-5, 443824/2014-2, 466650/2014-0]; Fundacao de Amparo a Pesquisa do Espirito Santo; CNPq; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior FX We want to thank the patients and families who agreed to participate in this study. We thank the Greenhouse Clinic team, especially Dr. Luis Henrique Casagrande, who allowed us to conduct this study in patients from this Clinic for Treatment of Mental Disorders and Drug Dependence, to use its facilities, and made all effort to help us. This work was supported by Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) (grant nos. 475232/2013-5, 443824/2014-2, and 466650/2014-0 to E.M.N.P.). E.M.N.P. received a researcher fellowship from Fundacao de Amparo a Pesquisa do Espirito Santo. E.K.B. and J.K. were recipients of student fellowships from CNPq and Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior. NR 56 TC 6 Z9 7 U1 3 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1461-1457 EI 1469-5111 J9 INT J NEUROPSYCHOPH JI Int. J. Neuropsychopharmacol. PD NOV PY 2015 VL 18 IS 12 AR UNSP pyv066 DI 10.1093/ijnp/pyv066 PG 11 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA CY6DV UT WOS:000366499000004 ER PT J AU Ekser, B Markmann, JF Tector, AJ AF Ekser, Burcin Markmann, James F. Tector, A. Joseph TI Current status of pig liver xenotransplantation SO INTERNATIONAL JOURNAL OF SURGERY LA English DT Review DE Acute liver failure; Liver; Pig; Nonhuman primate; Xenotransplantation ID PHAGOCYTOSIS IN-VITRO; NONHUMAN PRIMATE; HUMAN PLATELETS; BABOON; THROMBOCYTOPENIA; SURVIVAL; TRANSPLANTATION; XENOPERFUSION; RECEPTOR; TRANSFERASE AB The shortage of organs from deceased human donors is a major problem limiting the number of organs transplanted each year and results in the death of thousands of patients on the waiting list. Pigs are currently the preferred species for clinical organ xenotransplantation. Progress in genetically-engineered (GE) pig liver xenotransplantation increased graft and recipient survival from hours with unmodified pig livers to up to 9 days with normal to near-normal liver function. Deletion of genes such as GGTA1 (Gal-knockout pigs) or adding genes such as human complement regulatory proteins (hCD55, hCD46 expressing pigs) enabled hyperacute rejection to be overcome. Although survival up to 9 days was recorded, extended pig graft survival was not achieved due to lethal thrombocytopenia. The current status of GE pig liver xenotransplantation with world experience, potential factors causing thrombocytopenia, new targets on pig endothelial cells, and novel GE pigs with more genes deletion to avoid remaining antibody response, such as beta1,4-N-acetyl galactosaminyl transferase 2 (beta 4GalNT2), are discussed. (C) 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved. C1 [Ekser, Burcin; Tector, A. Joseph] Indiana Univ Sch Med, Dept Surg, Transplant Div, Indianapolis, IN 46202 USA. [Markmann, James F.] Massachusetts Gen Hosp, Dept Surg, Div Transplantat, Boston, MA 02114 USA. RP Ekser, B (reprint author), Indiana Univ Sch Med, Dept Surg, Transplant Div, 550 Univ Blvd,Room 4601, Indianapolis, IN 46202 USA. EM bekser@iupui.edu NR 33 TC 3 Z9 3 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1743-9191 EI 1743-9159 J9 INT J SURG JI Int. J. Surg. PD NOV PY 2015 VL 23 SI SI BP 240 EP 246 DI 10.1016/j.ijsu.2015.06.083 PN B PG 7 WC Surgery SC Surgery GA CY8ME UT WOS:000366661900009 PM 26190837 ER PT J AU Meier, RPH Navarro-Alvarez, N Morel, P Schuurman, HJ Strom, S Buhler, LH AF Meier, Raphael P. H. Navarro-Alvarez, Nalu Morel, Philippe Schuurman, Henk-Jan Strom, Stephen Buhler, Leo H. TI Current status of hepatocyte xenotransplantation SO INTERNATIONAL JOURNAL OF SURGERY LA English DT Review DE Acute liver failure; Alcoholic hepatitis; Animal models of liver failure; Cell transplantation; Innate immunity; Physiologic species incompatibilities; Porcine hepatocytes; Xenotransplantation ID ACUTE LIVER-FAILURE; GLYCOL) HYBRID MICROSPHERES; PORCINE HEPATOCYTES; XENOGENEIC HEPATOCYTES; CELL MICROENCAPSULATION; IMMUNODEFICIENT MICE; BIOARTIFICIAL LIVER; ENDOTHELIAL-CELLS; NONHUMAN-PRIMATES; TRANSPLANTATION AB The treatment of acute liver failure, a condition with high mortality, comprises optimal clinical care, and in severe cases liver transplantation. However, there are limitations in availability of organ donors. Hepatocyte transplantation is a promising alternative that could fill the medical need, in particular as the bridge to liver transplantation. Encapsulated porcine hepatocytes represent an unlimited source that could function as a bioreactor requiring minimal immunosuppression. Besides patients with acute liver failure, patients with alcoholic hepatitis who are unresponsive to a short course of corticosteroids are a target for hepatocyte transplantation. In this review we present an overview of the innate immune barriers in hepatocyte xenotransplantation, including the role of complement and natural antibodies; the role of phagocytic cells and ligands like CD47 in the regulation of phagocytic cells; and the role of Natural Killer cells. We present also some illustrations of physiological species incompatibilities in hepatocyte xenotransplantation, such as incompatibilities in the coagulation system. An overview of the methodology for cell microencapsulation is presented, followed by proof-of-concept studies in rodent and nonhuman primate models of fulminant liver failure: these studies document the efficacy of microencapsulated porcine hepatocytes which warrants progress towards clinical application. Lastly, we present an outline of a provisional clinical trial, that upon completion of preclinical work could start within the upcoming 2-3 years. (C) 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved. C1 [Meier, Raphael P. H.; Morel, Philippe; Schuurman, Henk-Jan; Buhler, Leo H.] Univ Hosp Geneva, Dept Surg, Visceral & Transplantat Surg, CH-1211 Geneva 14, Switzerland. [Meier, Raphael P. H.; Morel, Philippe; Schuurman, Henk-Jan; Buhler, Leo H.] Fac Med, CH-1211 Geneva 14, Switzerland. [Navarro-Alvarez, Nalu] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Transplantat Sci, Boston, MA USA. [Strom, Stephen] Karolinska Inst, Dept Lab Med, Cell Transplantat & Regenerat Med, Pathol, Stockholm, Sweden. RP Meier, RPH (reprint author), Univ Hosp Geneva, Dept Surg, Visceral & Transplantat Surg, 4 Rue Gabrielle Perret Gentil, CH-1211 Geneva 14, Switzerland. EM Raphael.meier@hcuge.ch NR 67 TC 3 Z9 3 U1 4 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1743-9191 EI 1743-9159 J9 INT J SURG JI Int. J. Surg. PD NOV PY 2015 VL 23 SI SI BP 273 EP 279 DI 10.1016/j.ijsu.2015.08.077 PN B PG 7 WC Surgery SC Surgery GA CY8ME UT WOS:000366661900014 PM 26361861 ER PT J AU Vagefi, PA Shah, JA Sachs, DH AF Vagefi, Parsia A. Shah, Jigesh A. Sachs, David H. TI Progress towards inducing tolerance of pig-to-primate xenografts SO INTERNATIONAL JOURNAL OF SURGERY LA English DT Review DE Transplant tolerance; Xenotransplantation; Animal models ID HEMATOPOIETIC-CELL TRANSPLANTATION; NONLETHAL PREPARATIVE REGIMEN; THYMIC LOBE TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; SWINE LEUKOCYTE ANTIGENS; NATURAL ANTIBODIES; MINIATURE SWINE; XENOGENEIC BARRIER; MIXED CHIMERISM; COMPOSITE THYMOKIDNEYS AB Xenotransplantation remains the best near-term solution to the shortage of transplantable organs that currently limits the field of transplantation. However, because the immune response to xenografts is considerably stronger than it is to allografts, the amount of non-specific immunosuppression required to avoid xenograft rejection may limit clinical applicability. For this reason, we consider it likely that the success of clinical xenotransplantation will depend on finding ways of safely inducing tolerance across xenogeneic barriers rather than relying entirely on non-specific immunosuppressive agents. In this laboratory, two approaches are being studied for the induction of pig-to-primate tolerance: a) the simultaneous transplantation of vascularized thymus and solid organs; and b) mixed hematopoietic chimerism. A summary of the development of these two approaches and their current status is the subject of this review. (C) 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved. C1 [Vagefi, Parsia A.; Shah, Jigesh A.; Sachs, David H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Transplantat Sci, Boston, MA USA. RP Sachs, DH (reprint author), Massachusetts Gen Hosp MGH East, Transplantat Biol Res Ctr, Ctr Transplantat Sci, Bldg 149,13th St,Suite 9008, Charlestown, MA 02129 USA. EM David.Sachs@tbrc.mgh.harvard.edu OI Shah, Jigesh/0000-0003-2097-0656 NR 42 TC 1 Z9 1 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1743-9191 EI 1743-9159 J9 INT J SURG JI Int. J. Surg. PD NOV PY 2015 VL 23 SI SI BP 291 EP 295 DI 10.1016/j.ijsu.2015.07.720 PN B PG 5 WC Surgery SC Surgery GA CY8ME UT WOS:000366661900017 PM 26296932 ER PT J AU Guercio, BJ Sato, K Niedzwiecki, D Ye, X Saltz, LB Mayer, RJ Mowat, RB Whittom, R Hantel, A Benson, A Atienza, D Messino, M Kindler, H Venook, A Hu, FB Ogino, S Wu, KN Willett, WC Giovannucci, EL Meyerhardt, JA Fuchs, CS AF Guercio, Brendan J. Sato, Kaori Niedzwiecki, Donna Ye, Xing Saltz, Leonard B. Mayer, Robert J. Mowat, Rex B. Whittom, Renaud Hantel, Alexander Benson, Al Atienza, Daniel Messino, Michael Kindler, Hedy Venook, Alan Hu, Frank B. Ogino, Shuji Wu, Kana Willett, Walter C. Giovannucci, Edward L. Meyerhardt, Jeffrey A. Fuchs, Charles S. TI Coffee Intake, Recurrence, and Mortality in Stage III Colon Cancer: Results From CALGB 89803 (Alliance) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FOOD-FREQUENCY QUESTIONNAIRE; PLASMA C-PEPTIDE; TYPE-2 DIABETES-MELLITUS; DIETARY GLYCEMIC LOAD; TOTAL-ENERGY-INTAKE; GROWTH-FACTOR-I; COLORECTAL-CANCER; DECAFFEINATED COFFEE; PROSPECTIVE COHORT; CHLOROGENIC ACID AB Purpose Observational studies have demonstrated increased colon cancer recurrence in states of relative hyperinsulinemia, including sedentary lifestyle, obesity, and increased dietary glycemic load. Greater coffee consumption has been associated with decreased risk of type 2 diabetes and increased insulin sensitivity. The effect of coffee on colon cancer recurrence and survival is unknown. Patients and Methods During and 6 months after adjuvant chemotherapy, 953 patients with stage III colon cancer prospectively reported dietary intake of caffeinated coffee, decaffeinated coffee, and nonherbal tea, as well as 128 other items. We examined the influence of coffee, nonherbal tea, and caffeine on cancer recurrence and mortality using Cox proportional hazards regression. Results Patients consuming 4 cups/d or more of total coffee experienced an adjusted hazard ratio (HR) for colon cancer recurrence or mortality of 0.58 (95% CI, 0.34 to 0.99), compared with never drinkers (P-trend = .002). Patients consuming 4 cups/d or more of caffeinated coffee experienced significantly reduced cancer recurrence or mortality risk compared with abstainers (HR, 0.48; 95% CI, 0.25 to 0.91; P-trend = .002), and increasing caffeine intake also conferred a significant reduction in cancer recurrence or mortality (HR, 0.66 across extreme quintiles; 95% CI, 0.47 to 0.93; P-trend = .006). Nonherbal tea and decaffeinated coffee were not associated with patient outcome. The association of total coffee intake with improved outcomes seemed consistent across other predictors of cancer recurrence and mortality. Conclusion Higher coffee intake may be associated with significantly reduced cancer recurrence and death in patients with stage III colon cancer. (C) 2015 by American Society of Clinical Oncology C1 [Guercio, Brendan J.; Ogino, Shuji; Giovannucci, Edward L.] Harvard Univ, Sch Med, Boston, MA USA. [Sato, Kaori; Mayer, Robert J.; Ogino, Shuji; Meyerhardt, Jeffrey A.; Fuchs, Charles S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hu, Frank B.; Ogino, Shuji; Wu, Kana; Willett, Walter C.; Giovannucci, Edward L.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. [Ogino, Shuji; Giovannucci, Edward L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Saltz, Leonard B.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Mowat, Rex B.] Toledo Community Hosp, Oncol Program, Toledo, OH USA. [Whittom, Renaud] Hop Sacre Coeur, Montreal, PQ H4J 1C5, Canada. [Hantel, Alexander] Loyola Univ, Stritch Sch Med, Naperville, IL USA. [Benson, Al] Northwestern Univ, Chicago, IL 60611 USA. [Kindler, Hedy] Univ Chicago, Chicago, IL 60637 USA. [Atienza, Daniel] Virginia Oncol Associates, Norfolk, VA USA. [Niedzwiecki, Donna; Ye, Xing] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Messino, Michael] Mission Hosp, Southeast Canc Control Consortium, Asheville, NC USA. [Venook, Alan] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. RP Fuchs, CS (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Room D1220, Boston, MA 02115 USA. EM charles_fuchs@dfci.harvard.edu OI Saltz, Leonard/0000-0001-8353-4670 FU National Cancer Institute of the National Institutes of Health [U10CA180821, U10CA180882, CA31946, CA33601, CA180820]; National Institutes of Health [CA32291, CA77651, CA45808, CA60138]; Perry S. Levy Fund for Gastrointestinal Cancer Research; Pfizer Oncology; National Cancer Institute [R01-CA118553, R01-CA149222, R01-CA169141, P50-CA127003] FX Supported by the National Cancer Institute of the National Institutes of Health Grants No. U10CA180821 and U10CA180882 to the Alliance for Clinical Trials in Oncology, CA31946 and CA33601 to the legacy Cancer and Leukemia Group B, and CA180820 to the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network. Additional support was provided by Grants No. CA32291, CA77651, CA45808, and CA60138 from National Institutes of Health, by a grant from the Perry S. Levy Fund for Gastrointestinal Cancer Research, and by Pharmacia & Upjohn Company, now Pfizer Oncology. C.S.F. and J.A.M. are supported in part by the National Cancer Institute (Grants No. R01-CA118553, R01-CA149222, R01-CA169141, and P50-CA127003). NR 59 TC 2 Z9 2 U1 3 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 1 PY 2015 VL 33 IS 31 BP 3598 EP + DI 10.1200/JCO.2015.61.5062 PG 13 WC Oncology SC Oncology GA CX9IU UT WOS:000366019800016 PM 26282659 ER PT J AU Keenan, T Moy, B Mroz, EA Ross, K Niemierko, A Rocco, JW Isakoff, S Ellisen, LW Bardia, A AF Keenan, Tanya Moy, Beverly Mroz, Edmund A. Ross, Kenneth Niemierko, Andrzej Rocco, James W. Isakoff, Steven Ellisen, Leif W. Bardia, Aditya TI Comparison of the Genomic Landscape Between Primary Breast Cancer in African American Versus White Women and the Association of Racial Differences With Tumor Recurrence SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID INTRATUMOR GENETIC-HETEROGENEITY; CHEMOTHERAPY INITIATION; UNITED-STATES; SURVIVAL; DISPARITIES; DIAGNOSIS; RACE; SUBTYPES; STAGE; RACE/ETHNICITY AB Purpose African American women are more likely to die as a result of breast cancer than white women. The influence of somatic genomic profiles on this racial disparity is unclear. We aimed to compare the racial distribution of tumor genomic characteristics and breast cancer recurrence. Methods We assessed white and African American women with stage I to III breast cancer diagnosed from 1988 to 2013 and primary tumors submitted to The Cancer Genome Atlas from 2010 to 2014. We used Cox proportional hazards models to evaluate the association of race and genetic traits with tumor recurrence. Results We investigated exome sequencing and gene expression data in 663 and 711 white and 105 and 159 African American women, respectively. African Americans had more TP53 mutations (42.9% v 27.6%; P = .003) and fewer PIK3CA mutations (20.0% v 33.9%; P = .008). Intratumor genetic heterogeneity was greater in African American than white tumors overall by 5.1 units (95% CI, 2.4 to 7.7) and within triple-negative tumors by 4.1 units (95% CI, 1.4 to 6.8). African Americans had more basal tumors by the 50-gene set predictor using the predication analysis of microarray method (PAM50; 39.0% v 18.6%; P < .001) and fewer PAM50 luminal A tumors (17.0% v 34.7%; P < .001). Among triple-negative subtypes, African Americans had more basal-like 1 and mesenchymal stem-like tumors. African Americans had a higher risk of tumor recurrence than whites (hazard ratio, 2.22; 95% CI, 1.05 to 4.67). Racial differences in TP53 mutation, PAM50 basal subtype, and triple-negative tumor prevalence but not intratumor genetic heterogeneity influenced the magnitude and significance of the racial disparity in tumor recurrence. Conclusion African Americans had greater intratumor genetic heterogeneity and more basal gene expression tumors, even within triple-negative breast cancer. This pattern suggests more aggressive tumor biology in African Americans than whites, which could contribute to racial disparity in breast cancer outcome. (C) 2015 by American Society of Clinical Oncology C1 [Keenan, Tanya; Moy, Beverly; Ross, Kenneth; Niemierko, Andrzej; Isakoff, Steven; Ellisen, Leif W.; Bardia, Aditya] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Mroz, Edmund A.; Rocco, James W.] Ohio State Univ, Wexner Med Ctr, Columbus, OH 43210 USA. [Mroz, Edmund A.; Rocco, James W.] Ohio State Univ, James Canc Ctr, Columbus, OH 43210 USA. RP Bardia, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Profess Off Bldg 214,10 N Grove St, Boston, MA 02114 USA. EM bardia.aditya@mgh.harvard.edu FU Jerry Younger Grant for Clinical and Translational Breast Cancer Research FX Supported in part by a Jerry Younger Grant for Clinical and Translational Breast Cancer Research. NR 36 TC 15 Z9 15 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 1 PY 2015 VL 33 IS 31 BP 3621 EP + DI 10.1200/JCO.2015.62.2126 PG 8 WC Oncology SC Oncology GA CX9IU UT WOS:000366019800019 PM 26371147 ER PT J AU Singh, H Longo, DL Chabner, BA AF Singh, Harshabad Longo, Dan L. Chabner, Bruce A. TI Improving Prospects for Targeting RAS SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CELL LUNG-CANCER; SYNTHETIC LETHAL INTERACTION; TRANSFERASE INHIBITOR R115777; METASTATIC COLORECTAL-CANCER; ADVANCED PANCREATIC-CANCER; ONCOGENIC K-RAS; PHASE-II; MUTANT RAS; GM-CSF; PROTEIN TRANSFERASE AB RAS mutations are among the most common oncogenic drivers in human cancers, affecting nearly a third of all solid tumors and around a fifth of common myeloid malignancies, but they have evaded therapeutic interventions, despite being the focus of intense research over the last three decades. Recent discoveries lend new understanding about the structure, function, and signaling of RAS and have opened new avenues for development of much needed new therapies. We discuss the various approaches under investigation to target mutant RAS proteins. The recent development of direct RAS inhibitors specific to KRAS G12C mutations represents a landmark discovery that promises to change the perception about RAS's druggability. Multiple clinical trials targeting synthetically lethal partners and/or downstream signaling partners of RAS are underway. Novel inhibitors targeting various arms of RAS processing and signaling have yielded encouraging results in the laboratory, but refinement of the drug-like properties of these molecules is required before they will be ready for the clinic. (C) 2015 by American Society of Clinical Oncology C1 [Singh, Harshabad; Chabner, Bruce A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Singh, Harshabad] Dana Farber Canc Inst, Boston, MA 02115 USA. [Longo, Dan L.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Chabner, BA (reprint author), Massachusetts Gen Hosp, Ctr Canc, 10 North Grove St, Boston, MA 02114 USA. EM bchabner@partners.org NR 102 TC 12 Z9 13 U1 2 U2 16 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 1 PY 2015 VL 33 IS 31 BP 3650 EP + DI 10.1200/JCO.2015.62.1052 PG 11 WC Oncology SC Oncology GA CX9IU UT WOS:000366019800023 PM 26371146 ER PT J AU Robson, ME Bradbury, AR Arun, B Domchek, SM Ford, JM Hampel, HL Lipkin, SM Syngal, S Wollins, DS Lindor, NM AF Robson, Mark E. Bradbury, Angela R. Arun, Banu Domchek, Susan M. Ford, James M. Hampel, Heather L. Lipkin, Stephen M. Syngal, Sapna Wollins, Dana S. Lindor, Noralane M. TI American Society of Clinical Oncology Policy Statement Update: Genetic and Genomic Testing for Cancer Susceptibility SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID INCIDENTAL FINDINGS; COLORECTAL-CANCER; RISK; RECOMMENDATIONS; PANEL; MORTALITY AB The American Society of Clinical Oncology (ASCO) has long affirmed that the recognition and management of individuals with an inherited susceptibility to cancer are core elements of oncology care. ASCO released its first statement on genetic testing in 1996 and updated that statement in 2003 and 2010 in response to developments in the field. In 2014, the Cancer Prevention and Ethics Committees of ASCO commissioned another update to reflect the impact of advances in this area on oncology practice. In particular, there was an interest in addressing the opportunities and challenges arising from the application of massively parallel sequencingalso known as next-generation sequencingto cancer susceptibility testing. This technology introduces a new level of complexity into the practice of cancer risk assessment and management, requiring renewed effort on the part of ASCO to ensure that those providing care to patients with cancer receive the necessary education to use this new technology in the most effective, beneficial manner. The purpose of this statement is to explore the challenges of new and emerging technologies in cancer genetics and provide recommendations to ensure their optimal deployment in oncology practice. Specifically, the statement makes recommendations in the following areas: germline implications of somatic mutation profiling, multigene panel testing for cancer susceptibility, quality assurance in genetic testing, education of oncology professionals, and access to cancer genetic services. (C) 2015 by American Society of Clinical Oncology C1 [Robson, Mark E.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA. [Robson, Mark E.; Lipkin, Stephen M.] Weill Cornell Med Coll, New York, NY USA. [Bradbury, Angela R.; Domchek, Susan M.] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Arun, Banu] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Ford, James M.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Hampel, Heather L.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Syngal, Sapna] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wollins, Dana S.] Amer Soc Clin Oncol, Alexandria, VA USA. [Lindor, Noralane M.] Mayo Clin, Scottsdale, AZ USA. RP Robson, ME (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA. EM robsonm@mskcc.org OI Robson, Mark/0000-0002-3109-1692 FU AstraZeneca; AbbVie; Myriad Genetics; Biomarin; Hill-Rom; Susan G. Komen for the Cure; Clovis Oncology; InVitae; Varian Medical Systems; Natera FX AstraZeneca (Inst), AbbVie (Inst), Myriad Genetics (Inst), Biomarin (Inst); Myriad Genetics, Hill-Rom (I); Susan G. Komen for the Cure; AstraZeneca (Inst), Clovis Oncology (Inst), AbbVie (Inst); Myriad Genetics (Inst), InVitae (Inst), Varian Medical Systems (Inst), Natera (Inst); Myriad Genetics NR 28 TC 46 Z9 47 U1 5 U2 10 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 1 PY 2015 VL 33 IS 31 BP 3660 EP + DI 10.1200/JCO.2015.63.0996 PG 10 WC Oncology SC Oncology GA CX9IU UT WOS:000366019800024 PM 26324357 ER PT J AU Grosz, PG Patel-Grosz, P Fedorenko, E Gibson, E AF Grosz, Patrick G. Patel-Grosz, Pritty Fedorenko, Evelina Gibson, Edward TI Constraints on Donkey Pronouns SO JOURNAL OF SEMANTICS LA English DT Article ID REFERENCE RESOLUTION; TIME-COURSE; INFORMATION; BINDING; SENTENCES; ANAPHORA AB This article reports on an experimental study of donkey pronouns, pronouns (e.g. it) whose meaning covaries with that of a non-pronominal noun phrase (e.g. a donkey) even though they are not in a structural relationship that is suitable for quantifier-variable binding. We investigate three constraints, (i) the preference for the presence of an overt NP antecedent that is not part of another word, (ii) the salience of the position of an antecedent that is part of another word, and (iii) the uniqueness of an intended antecedent (in terms of world knowledge). We compare constructions in which intended antecedents occur in a context such as who owns an N / who is an N-owner with constructions of the type who was without an N / who was N-less. Our findings corroborate the existence of the overt NP antecedent constraint, and also show that the salience of an unsuitable antecedent's position matters. Furthermore, our findings show that uniqueness only matters in the N-less type construction and not in the N-owner type construction; we conclude that this supports a potential approach in terms of dynamic semantics over a competing e-type approach. C1 [Grosz, Patrick G.] Univ Tubingen, Deutsch Seminar, D-72074 Tubingen, Germany. [Patel-Grosz, Pritty] Univ Tubingen, SFB833, D-72074 Tubingen, Germany. [Fedorenko, Evelina] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Gibson, Edward] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Grosz, PG (reprint author), Univ Tubingen, Deutsch Seminar, Wilhelmstr 50, D-72074 Tubingen, Germany. EM patrick.grosz@uni-tuebingen.de; pritty.patel-grosz@uni-tuebingen.de; efedoren@nmr.mgh.harvard.edu; egibson@mit.edu FU Daimler and Benz Foundation [32-01/12]; University of Tubingen [09021401] FX The authors would like to thank Adam Albright, Luis Alonso-Ovalle, Mark Baltin, Daniel Buering, Sigrid Beck, Paula Menendez-Benito, Jeroen van Craenenbroeck, Gennaro Chierchia, Kai von Fintel, Danny Fox, Bart Geurts, Martin Hackl, Irene Heim, Sabine Iatridou, Florian Jaeger, Kyle Johnson, Nathan Klinedinst, Tom Leu, Alec Marantz, Rick Nouwen, Steve Piantadosi, David Pesetsky, Masha Polinsky, Uli Sauerland, Philippe Schlenker, Florian Schwarz, Anna Szabolcsi, Igor Yanovich, two anonymous Journal of Semantics reviewers, and the audiences at the 22nd CUNY Conference on Human Sentence Processing, CUNY Syntax Supper, MIT Ling-Lunch, MIT LF-RG, SNEWS UMass Amherst and Sinn und Bedeutung 14. During later stages of this research, Patrick Grosz was partially funded by grant 32-01/12 from the Daimler and Benz Foundation and by grant 09021401 from the University of Tubingen. NR 60 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0167-5133 EI 1477-4593 J9 J SEMANT JI J. Semant. PD NOV PY 2015 VL 32 IS 4 BP 619 EP 648 DI 10.1093/jos/ffu009 PG 30 WC Linguistics; Language & Linguistics SC Linguistics GA CY8AP UT WOS:000366631100002 ER PT J AU Marutani, E Yamada, M Ida, T Tokuda, K Ikeda, K Kai, S Shirozu, K Hayashida, K Kosugi, S Hanaoka, K Kaneki, M Akaike, T Ichinose, F AF Marutani, Eizo Yamada, Marina Ida, Tomoaki Tokuda, Kentaro Ikeda, Kohei Kai, Shinichi Shirozu, Kazuhiro Hayashida, Kei Kosugi, Shizuko Hanaoka, Kenjiro Kaneki, Masao Akaike, Takaaki Ichinose, Fumito TI Thiosulfate Mediates Cytoprotective Effects of Hydrogen Sulfide Against Neuronal Ischemia SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE apoptosis; cerebral ischemia; hydrogen sulfide; sulfidation; thiosulfate ID SODIUM THIOSULFATE; IMPROVES SURVIVAL; CARDIAC-ARREST; MICE; BRAIN; PERSULFIDES; GENERATION; CASPASE-3; SULFUR; DAMAGE AB Background-Hydrogen sulfide (H2S) exhibits protective effects in various disease models including cerebral ischemia-reperfusion (I/R) injury. Nonetheless, mechanisms and identity of molecules responsible for neuroprotective effects of H2S remain incompletely defined. In the current study, we observed that thiosulfate, an oxidation product of H2S, mediates protective effects of an H2S donor compound sodium sulfide (Na2S) against neuronal I/R injury. Methods and Results-We observed that thiosulfate in cell culture medium is not only required but also sufficient to mediate cytoprotective effects of Na2S against oxygen glucose deprivation and reoxygenation of human neuroblastoma cell line (SH-SY5Y) and murine primary cortical neurons. Systemic administration of sodium thiosulfate (STS) improved survival and neurological function of mice subjected to global cerebral I/R injury. Beneficial effects of STS, as well as Na2S, were associated with marked increase of thiosulfate, but not H2S, in plasma and brain tissues. These results suggest that thiosulfate is a circulating "carrier" molecule of beneficial effects of H2S. Protective effects of thiosulfate were associated with inhibition of caspase-3 activity by persulfidation at Cys163 in caspase-3. We discovered that an SLC13 family protein, sodium sulfate cotransporter 2 (SLC13A4, NaS-2), facilitates transport of thiosulfate, but not sulfide, across the cell membrane, regulating intracellular concentrations and thus mediating cytoprotective effects of Na2S and STS. Conclusions-The protective effects of H2S are mediated by thiosulfate that is transported across cell membrane by NaS-2 and exerts antiapoptotic effects via persulfidation of caspase-3. Given the established safety track record, thiosulfate may be therapeutic against ischemic brain injury. C1 [Marutani, Eizo; Yamada, Marina; Tokuda, Kentaro; Ikeda, Kohei; Kai, Shinichi; Shirozu, Kazuhiro; Hayashida, Kei; Kosugi, Shizuko; Kaneki, Masao; Ichinose, Fumito] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA 02129 USA. [Marutani, Eizo; Yamada, Marina; Tokuda, Kentaro; Ikeda, Kohei; Kai, Shinichi; Shirozu, Kazuhiro; Hayashida, Kei; Kosugi, Shizuko; Kaneki, Masao; Ichinose, Fumito] Harvard Univ, Sch Med, Boston, MA USA. [Yamada, Marina; Kaneki, Masao] Shriners Hosp Children, Boston, MA USA. [Ida, Tomoaki; Akaike, Takaaki] Tohoku Univ, Grad Sch Med, Dept Environm Hlth Sci & Mol Toxicol, Sendai, Miyagi 980, Japan. [Hanaoka, Kenjiro] Univ Tokyo, Grad Sch Pharmaceut Sci, Tokyo 1138654, Japan. RP Marutani, E (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 149 13th St,4309, Charlestown, MA 02129 USA. EM emarutani@mgh.harvard.edu FU National Institutes of Health [HL101930] FX This work was supported by National Institutes of Health grant HL101930 to Dr Ichinose. NR 37 TC 6 Z9 6 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD NOV PY 2015 VL 4 IS 11 AR e002125 DI 10.1161/JAHA.115.002125 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CY7UU UT WOS:000366615600005 ER PT J AU Shi, HT Wang, XJ Li, J Song, GF Huang, ZY Guo, XY Guo, JJ Lv, ZY Li, HW Ge, JB Cui, J Qi, GM AF Shi, Hong-tao Wang, Xiao-jing Li, Jun Song, Gui-fang Huang, Zhe-yong Guo, Xiang-yu Guo, Jun-jie Lv, Zhi-yang Li, Hong-wei Ge, Jun-bo Cui, Jie Qi, Guan-ming TI Association of Left Ventricular Hypertrophy With a Faster Rate of Renal Function Decline in Elderly Patients With Non-End-Stage Renal Disease SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE chronic kidney disease; left ventricular hypotrophy; left ventricular mass index; non-end-stage renal disease; rapid kidney function decline ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; ECHOCARDIOGRAPHIC-ASSESSMENT; GENERAL-POPULATION; CLINICAL-PRACTICE; BLOOD-PRESSURE; RISK-FACTORS; PATHOGENESIS; GEOMETRY AB Background-Several studies have indicated that chronic kidney disease is independently associated with the presence of left ventricular hypertrophy (LVH). However, little clinical data are currently available regarding the detailed correlation between LVH and renal function in elderly patients with non-end-stage renal disease. Methods and Results-A total of 300 in-and outpatients (more than 60 years of age, non-end-stage renal disease), 251 with LVH and 49 without LVH, seen at Beijing Friendship Hospital from January 2000 to December 2010 were included in this retrospective study. One observation period of 12 months was used to detect rapid kidney function decline. The evaluations of cardiac structure and function were performed via echocardiography. The multivariable logistic analysis showed patients with LVH had a much higher risk of rapid kidney function decline than those without LVH. Additionally, the baseline left ventricular mass index was 140 (125-160) g/m(2) in the non-chronic kidney disease group, 152 (130-175) g/m(2) in the mild chronic kidney disease group (estimated glomerular filtration rate (eGFR)>= 60 ml/min/1.73 m(2)), and 153 (133-183) g/m(2) in the severe chronic kidney disease group (eGFR<60 ml/min/1.73 m(2)), with a significant difference (P=0.009). Conclusions-Our data demonstrate that a high rate of renal function decline contributes to pathological LVH in non-end-stage renal disease elderly patients and that LVH is positively associated with renal function decline followed by an increased risk of rapid kidney function decline. C1 [Shi, Hong-tao; Wang, Xiao-jing; Li, Hong-wei; Qi, Guan-ming] Capital Med Univ, Beijing Friendship Hosp, Dept Cardiol, Beijing 100050, Peoples R China. [Guo, Xiang-yu] Capital Med Univ, Sch Pharmaceut Sci, Beijing 100050, Peoples R China. [Shi, Hong-tao; Huang, Zhe-yong; Guo, Jun-jie; Ge, Jun-bo] Fudan Univ, Zhongshan Hosp, Shanghai Inst Cardiovasc Dis, Dept Cardiol, Shanghai 200433, Peoples R China. [Li, Jun; Song, Gui-fang] Qingdao Univ, Qingdao Med Coll, Yuhuangding Hosp, Dept Cardiol, Yantai, Shandong, Peoples R China. [Guo, Jun-jie] Qingdao Univ, Affiliated Hosp, Dept Cardiol, Qingdao 266071, Shandong, Peoples R China. [Lv, Zhi-yang] China Three Gorges Univ, Inst Cardiovasc Dis, Yichang Cent Peoples Hosp, Dept Cardiol, Yichang, Hubei Province, Peoples R China. [Cui, Jie] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Nephrol, Boston, MA USA. RP Qi, GM (reprint author), Capital Med Univ, Beijing Friendship Hosp, 95 Yongan Rd, Beijing 100050, Peoples R China. EM jbge@zs-hospital.sh.cn; JCUI2@mgh.harvard.edu; guanming_qi@126.com FU National Natural Science Foundation of China [81300121, 81370003, 81570223, 81400263]; Basic-Clinical Cooperation Project of Chinese Capital Medical University [13JL59] FX This work was supported by National Natural Science Foundation of China (81300121, 81370003, 81570223, and 81400263) and Basic-Clinical Cooperation Project of Chinese Capital Medical University (13JL59). NR 28 TC 0 Z9 0 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD NOV PY 2015 VL 4 IS 11 AR e002213 DI 10.1161/JAHA.115.002213 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CY7UU UT WOS:000366615600008 ER PT J AU Day, FR Bulik-Sullivan, B Hinds, DA Finucane, HK Murabito, JM Tung, JY Ong, KK Perry, JRB AF Day, Felix R. Bulik-Sullivan, Brendan Hinds, David A. Finucane, Hilary K. Murabito, Joanne M. Tung, Joyce Y. Ong, Ken K. Perry, John R. B. TI Shared genetic aetiology of puberty timing between sexes and with health-related outcomes SO NATURE COMMUNICATIONS LA English DT Article ID GENOME-WIDE ASSOCIATION; RETINOID-X-RECEPTOR; LIFE-COURSE; BODY-MASS; MENARCHE; LOCI; AGE; METAANALYSIS; OBESITY; VARIANTS AB Understanding of the genetic regulation of puberty timing has come largely from studies of rare disorders and population-based studies in women. Here, we report the largest genomic analysis for puberty timing in 55,871 men, based on recalled age at voice breaking. Analysis across all genomic variants reveals strong genetic correlation (0.74, P = 2.7 x 10(-70)) between male and female puberty timing. However, some loci show sex-divergent effects, including directionally opposite effects between sexes at the SIM1/MCHR2 locus (P-heterogeneity = 1.6 x 10(-12)). We find five novel loci for puberty timing (P<5 x 10(-8)), in addition to nine signals in men that were previously reported in women. Newly implicated genes include two retinoic acid-related receptors, RORB and RXRA, and two genes reportedly disrupted in rare disorders of puberty, LEPR and KAL1. Finally, we identify genetic correlations that indicate shared aetiologies in both sexes between puberty timing and body mass index, fasting insulin levels, lipid levels, type 2 diabetes and cardiovascular disease. C1 [Day, Felix R.; Ong, Ken K.; Perry, John R. B.] Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Inst Metab Sci, Cambridge CB2 0QQ, England. [Bulik-Sullivan, Brendan] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Bulik-Sullivan, Brendan] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Bulik-Sullivan, Brendan] Broad Inst, Med & Populat Genet, Cambridge, MA 02142 USA. [Hinds, David A.; Tung, Joyce Y.] 23andMe Inc, Mountain View, CA 94041 USA. [Finucane, Hilary K.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Finucane, Hilary K.] MIT, Dept Math, Cambridge, MA 02139 USA. [Murabito, Joanne M.] NHLBIs & Boston Univ Framingham Heart Study, Framingham, MA 01702 USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA. [Ong, Ken K.] Univ Cambridge, Dept Paediat, Cambridge CB2 0QQ, England. RP Perry, JRB (reprint author), Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Inst Metab Sci, Box 285,Cambridge Biomed Campus, Cambridge CB2 0QQ, England. EM john.perry@mrc-epid.cam.ac.uk FU Medical Research Council [U106179472, MC_U106179472, U106179471, MC_U106179471]; National Human Genome Research Institute of the National Institutes of Health [R44HG006981]; Fannie and John Hertz Foundation FX This work was supported by the Medical Research Council [U106179472; MC_U106179472; U106179471; MC_U106179471] and the National Human Genome Research Institute of the National Institutes of Health (grant number R44HG006981 to 23andMe). We thank the research participants and employees of 23andMe for making this work possible. HKF is supported by the Fannie and John Hertz Foundation. NR 29 TC 5 Z9 5 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD NOV PY 2015 VL 6 AR 8842 DI 10.1038/ncomms9842 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA CY3GC UT WOS:000366295800009 PM 26548314 ER PT J AU Scales, CD Bergman, J Carter, S Jack, G Saigal, CS Litwin, MS AF Scales, Charles D., Jr. Bergman, Jonathan Carter, Stacey Jack, Gregory Saigal, Christopher S. Litwin, Mark S. CA NIDDK Urologic Dis Amer Project TI Quality of Acute Care for Patients With Urinary Stones in the United States SO UROLOGY LA English DT Article ID KIDNEY-STONES; RADIATION-EXPOSURE; CT SCANS; RISK; UROLITHIASIS; PREVALENCE; MANAGEMENT; PATTERNS; CALCULI; TRENDS AB OBJECTIVE To describe guideline adherence for patients with suspected upper tract stones. PATIENTS AND METHODS We performed a cross-sectional analysis of visits recorded by the National Hospital Ambulatory Medical Care Survey (emergency department [ED] component) in 2007-2010 (most recent data). We assessed adherence to clinical guidelines for diagnostic laboratory testing, imaging, and pharmacologic therapy. Multivariable regression models controlled for important covariates. RESULTS An estimated 4,956,444 ED visits for patients with suspected kidney stones occurred during the study period. Guideline adherence was highest for diagnostic imaging, with 3,122,229 (63%) visits providing optimal imaging. Complete guideline-based laboratory testing occurred in only 2 of every 5 visits. Pharmacologic therapy to facilitate stone passage was prescribed during only 17% of eligible visits. In multivariable analysis of guideline adherence, we found little variation by patient, provider, or facility characteristics. CONCLUSION Guideline-recommended care was absent from a substantial proportion of acute care visits for patients with suspected kidney stones. These failures of care delivery likely increase costs and temporary disability. Targeted interventions to improve guideline adherence should be designed and evaluated to improve care for patients with symptomatic kidney stones. Published by Elsevier Inc. C1 Univ Calif Los Angeles, Robert Wood Johnson Fdn, Clin Scholars Program, Los Angeles, CA USA. US Dept Vet Affairs, Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Family Med, Los Angeles, CA 90095 USA. RAND Corp, Santa Monica, CA USA. Univ Calif Los Angeles, Dept Hlth Policy & Management, Fielding Sch Publ Hlth, Los Angeles, CA USA. RP Scales, CD (reprint author), Duke Clin Res Inst, Div Urol Surg, DUMC 3707, Durham, NC 27710 USA. EM Chuck.scales@duke.edu FU Robert Wood Johnson Foundation Clinical Scholars program; U.S. Department of Veterans Affairs; Urologic Diseases in America Project, through the National Institute of Diabetes and Digestive and Kidney Diseases; National Library of Medicine [HHSN276201200016C] FX Charles D. Scales and Jonathan Bergman were supported by the Robert Wood Johnson Foundation Clinical Scholars program and the U.S. Department of Veterans Affairs during conduct of this research. Christopher S. Saigal and Mark S. Litwin were supported by the Urologic Diseases in America Project, through the National Institute of Diabetes and Digestive and Kidney Diseases and the National Library of Medicine (HHSN276201200016C). NR 27 TC 1 Z9 1 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD NOV PY 2015 VL 86 IS 5 BP 914 EP 921 DI 10.1016/j.urology.2015.07.040 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA CY5RZ UT WOS:000366466400016 PM 26335495 ER PT J AU Byun, S Namba, T Lee, SW AF Byun, Sanguine Namba, Takushi Lee, Sam W. TI Losing p53 loosens up ER-stress SO AGING-US LA English DT Editorial Material DE p53; ER stress ID ENDOPLASMIC-RETICULUM C1 [Lee, Sam W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Lee, Sam W.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Lee, SW (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM swlee@mgh.harvard.edu NR 7 TC 0 Z9 0 U1 0 U2 0 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1945-4589 J9 AGING-US JI Aging-US PD NOV PY 2015 VL 7 IS 11 BP 895 EP 896 PG 2 WC Cell Biology SC Cell Biology GA CY4HR UT WOS:000366369700002 PM 26584019 ER PT J AU Ross, C Salmon, A Strong, R Fernandez, E Javors, M Richardson, A Tardif, S AF Ross, Corinna Salmon, Adam Strong, Randy Fernandez, Elizabeth Javors, Marty Richardson, Arlan Tardif, Suzette TI Metabolic consequences of long-term rapamycin exposure on common marmoset monkeys (Callithrix jacchus) SO AGING-US LA English DT Article DE nonhuman primate; antiaging; longevity; healthspan; animal models; sirolimus ID HIGH-FAT DIET; INDUCED INSULIN-RESISTANCE; LIFE-SPAN; GLUCOSE-INTOLERANCE; TRANSPLANT RECIPIENTS; MAMMALIAN TARGET; NONHUMAN PRIMATE; MTOR INHIBITION; FOOD-INTAKE; MALE-MICE AB Rapamycin has been shown to extend lifespan in rodent models, but the effects on metabolic health and function have been widely debated in both clinical and translational trials. Prior to rapamycin being used as a treatment to extend both lifespan and healthspan in the human population, it is vital to assess the side effects of the treatment on metabolic pathways in animal model systems, including a closely related non-human primate model. In this study, we found that long-term treatment of marmoset monkeys with orally-administered encapsulated rapamycin resulted in no overall effects on body weight and only a small decrease in fat mass over the first few months of treatment. Rapamycin treated subjects showed no overall changes in daily activity counts, blood lipids, or significant changes in glucose metabolism including oral glucose tolerance. Adipose tissue displayed no differences in gene expression of metabolic markers following treatment, while liver tissue exhibited suppressed G6Pase activity with increased PCK and GPI activity. Overall, the marmosets revealed only minor metabolic consequences of chronic treatment with rapamycin and this adds to the growing body of literature that suggests that chronic and/or intermittent rapamycin treatment results in improved health span and metabolic functioning. The marmosets offer an interesting alternative animal model for future intervention testing and translational modeling. C1 [Ross, Corinna] Texas A&M Univ, Dept Arts & Sci, San Antonio, TX 78224 USA. [Ross, Corinna; Salmon, Adam; Strong, Randy; Fernandez, Elizabeth; Javors, Marty; Tardif, Suzette] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78224 USA. [Salmon, Adam; Fernandez, Elizabeth; Javors, Marty] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78224 USA. [Richardson, Arlan] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK 73104 USA. [Richardson, Arlan] Oklahoma City VA Med Ctr, Oklahoma City, OK 73104 USA. [Tardif, Suzette] Southwest Natl Primate Res Ctr, Texas Biomed Res Inst, San Antonio, TX 78224 USA. RP Ross, C (reprint author), Texas A&M Univ, Dept Arts & Sci, San Antonio, TX 78224 USA. EM cnross@tamusa.tamus.edu FU Barshop Institute for Longevity and Aging Studies; Glenn Foundation; San Antonio Nathan Shock Center of Excellence in the Basic Biology of Aging; Southwest National Primate Research Center [P51-OD-13986] FX This research was financially supported by the Barshop Institute for Longevity and Aging Studies, the Glenn Foundation, the San Antonio Nathan Shock Center of Excellence in the Basic Biology of Aging and the Southwest National Primate Research Center (P51-OD-13986). NR 52 TC 5 Z9 5 U1 2 U2 2 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1945-4589 J9 AGING-US JI Aging-US PD NOV PY 2015 VL 7 IS 11 BP 964 EP 973 PG 10 WC Cell Biology SC Cell Biology GA CY4HR UT WOS:000366369700011 PM 26568298 ER PT J AU Kaul, S Kirchhoff, AC Morden, NE Vogeli, CS Campbell, EG AF Kaul, Sapna Kirchhoff, Anne C. Morden, Nancy E. Vogeli, Christine S. Campbell, Eric G. TI Physician Response to Patient Request for Unnecessary Care SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID US HEALTH-CARE; QUALITY IMPROVEMENT; PROFESSIONALISM; PERCEPTIONS; PERFORMANCE; WASTE; COST; REFERRALS; MEDICARE; INDUSTRY AB Objectives: Evaluating unnecessary US medical practices, and the strategies that reduce them, are increasingly recognized as crucial to healthcare financing sustainability. Provider factors are known to affect unnecessary medical practices, yet little is known about how physician responses to patient requests for unnecessary care affect these practices. Among primary care physicians (PCPs), we investigated 2 types of unnecessary medical practices triggered by patient requests: a) unnecessary specialty referrals and b) prescriptions for brand-name drugs when generic alternatives are available. Study Design: We used data from a survey of a nationally representative sample of 840 US PCPs in 2009. Response rates for family practice (n = 274), internal medicine (n = 257), and pediatrics (n = 309) were 67.5%, 60.8%, and 72.7%, respectively. Results: In response to patient requests, 51.9% of PCPs reported making unnecessary specialty referrals and 38.7% prescribed brand-name drugs. Family physicians (odds ratio [OR], 2.77; 95% CI, 1.77-4.34) and internal medicine physicians (OR, 4.51; 95% CI, 2.87-7.06) were more likely than pediatricians to prescribe brandname drugs. PCP specialty was similarly associated with unnecessary referrals. Other predictors of acquiescence to patient requests included interactions with drug/ device representatives, more years of clinical experience, seeing fewer safety net patients, and solo/2-person practice organizations. Area-level Medicare spending was not associated with the 2 unnecessary practices. Conclusions: Many PCPs reported acquiescing to patient requests for unnecessary care. Provider and organizational factors predicted this behavior. Policies aimed at reducing such practice could improve care quality and lower cost. Patient and physician incentives that can potentially reduce unnecessary medical practices warrant exploration. C1 [Kaul, Sapna] Univ Texas Med Branch, Dept Prevent Med & Community Hlth, Galveston, TX 77555 USA. [Kirchhoff, Anne C.] Univ Utah, Dept Pediat, Huntsman Canc Inst, Salt Lake City, UT USA. [Morden, Nancy E.] Dartmouth Inst Hlth Policy & Clin Practice, Lebanon, NH USA. [Vogeli, Christine S.; Campbell, Eric G.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Boston, MA 02114 USA. [Campbell, Eric G.] Harvard Univ, Sch Med, Boston, MA USA. RP Kaul, S (reprint author), Univ Texas Med Branch, Dept Prevent Med & Community Hlth, 301 Univ Blvd, Galveston, TX 77555 USA. EM sakaul@UTMB.EDU FU Institute on Medicine as a Profession at Columbia University, New York, NY FX This study was funded by the Institute on Medicine as a Profession at Columbia University, New York, NY. NR 34 TC 1 Z9 1 U1 3 U2 7 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD NOV PY 2015 VL 21 IS 11 BP 823 EP 832 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA CX8ZN UT WOS:000365994500007 PM 26633255 ER PT J AU Likosky, DS Wallace, AS Prager, RL Jacobs, JP Zhang, M Harrington, SD Saha-Chaudhuri, P Theurer, PF Fishstrom, A Dokholyan, RS Shahian, DM Rankin, JS AF Likosky, Donald S. Wallace, Amelia S. Prager, Richard L. Jacobs, Jeffrey P. Zhang, Min Harrington, Steven D. Saha-Chaudhuri, Paramita Theurer, Patricia F. Fishstrom, Astrid Dokholyan, Rachel S. Shahian, David M. Rankin, J. Scott CA Michigan Soc Thoracic Cardiovasc S TI Sources of Variation in Hospital-Level Infection Rates After Coronary Artery Bypass Grafting: An Analysis of The Society of Thoracic Surgeons Adult Heart Surgery Database SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 51st Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 24-28, 2015 CL San Diego, CA SP Soc Thorac Surg ID LONG-TERM SURVIVAL; CARDIAC-SURGERY; BLOOD CONSERVATION; QUALITY; MORTALITY; COMPLICATIONS; MEDIASTINITIS; TRANSFUSION; IMPROVEMENT; COSTS AB Background. Patients undergoing coronary artery bypass grafting (CABG) are at risk for a variety of infections. Investigators have focused on predictors of these adverse sequelae, but less attention has been focused on characterizing hospital-level variability in these outcomes. Methods. Between July 2011 and December 2013, The Society of Thoracic Surgeons Adult Cardiac Surgery Database shows 365,686 patients underwent isolated CABG in 1,084 hospitals. Hospital-acquired infections (HAIs) were defined as pneumonia, sepsis/septicemia, deep sternal wound infection/mediastinitis, vein harvest/cannulation site infection, or thoracotomy infection. Hospitals were ranked by their HAI rate as low(<= 10th percentile), medium (10th to 90th percentile), and high (>90th percentile). Differences in perioperative factors and composite morbidity and mortality end points across these groups were determined using the Wilcoxon rank sum and chi(2) tests. Results. HAIs occurred among 3.97% of patients overall, but rates varied across hospital groups (low: <0.84%, medium: 0.84% to 8.41%, high: >8.41%). Pneumonia (2.98%) was the most common HAI, followed by sepsis/septicemia (0.84%). Patients at high-rate hospitals more often smoked, had diabetes, chronic lung disease, New York Heart Association Functional Classification III to IV, and received blood products (p < 0.001); however, they less often were prescribed the appropriate antibiotics (p < 0.001). Major morbidity and mortality occurred among 12.3% of patients, although this varied by hospital group (low: 8.6%, medium: 12.3%, high: 17.9%; p < 0.001). Conclusions. Substantial hospital-level variation exists in postoperative HAIs among patients undergoing CABG, driven predominantly by pneumonia. Given the relatively small absolute differences in comorbidities across hospital groups, our findings suggest factors other than case mix may explain the observed variation in HAI rates. (C) 2015 by The Society of Thoracic Surgeons C1 Univ Michigan, Dept Cardiac Surg, Sect Hlth Serv Res & Qual, Ann Arbor, MI USA. Michigan Soc Thorac & Cardiovasc Surg Qual Collab, Ann Arbor, MI USA. Univ Michigan, Dept Cardiac Surg, Ann Arbor, MI USA. Duke Univ, Duke Clin Res Inst, Durham, NC USA. Johns Hopkins Univ, Sch Med, Dept Surg, Div Cardiac Surg, Baltimore, MD 21205 USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Henry Ford Macomb Hosp, Inst Heart & Vasc, Dept Cardiac Surg, Clinton Township, MI USA. Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Cardiac Surg, Boston, MA USA. Vanderbilt Univ, Nashville, TN 37235 USA. RP Likosky, DS (reprint author), Frankel Cardiovasc Ctr, Dept Cardiac Surg, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM likosky@umich.edu OI Saha Chaudhuri, Paramita/0000-0003-1987-320X FU AHRQ HHS [R01-HS-022535, R03 HS022909, R03-HS-022909, R01 HS022535] NR 24 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD NOV PY 2015 VL 100 IS 5 BP 1570 EP 1576 DI 10.1016/j.athoracsur.2015.05.015 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CX6OM UT WOS:000365820400022 PM 26321440 ER PT J AU Goldberg, J Paugh, TA Dickinson, TA Fuller, J Paone, G Theurer, PF Shann, KG Sundt, TM Prager, RL Likosky, DS AF Goldberg, Joshua Paugh, Theron A. Dickinson, Timothy A. Fuller, John Paone, Gaetano Theurer, Patty F. Shann, Kenneth G. Sundt, Thoralf M. Prager, Richard L. Likosky, Donald S. CA PERForm Registry Michigan Soc Thoracic Cardiovasc S TI Greater Volume of Acute Normovolemic Hemodilution May Aid in Reducing Blood Transfusions After Cardiac Surgery SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 51st Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 24-28, 2015 CL San Diego, CA SP Soc Thorac Surg ID CARDIOPULMONARY BYPASS; CELL; METAANALYSIS; MORBIDITY; MORTALITY AB Background. Perioperative red blood cell transfusions (RBC) are associated with increased morbidity and mortality after cardiac surgery. Acute normovolemic hemodilution (ANH) is recommended to reduce perioperative transfusions; however, supporting data are limited and conflicting. We describe the relationship between ANH and RBC transfusions after cardiac surgery using a multi-center registry. Methods. We analyzed 13,534 patients undergoing cardiac surgery between 2010 and 2014 at any of the 26 hospitals participating in a prospective cardiovascular perfusion database. The volume of ANH (no ANH, <400 mL, 400 to 799 mL, >= 800 mL) was recorded and linked to each center's surgical data. We report adjusted relative risks reflecting the association between the use and amount of ANH and the risk of perioperative RBC transfusion. Results were adjusted for preoperative risk factors, procedure, body surface area, preoperative hematocrit, and center. Results. The ANH was used in 17% of the patients. ANH was associated with a reduction in RBC transfusions (RRadj [adjusted risk ratio] 0.74, p < 0.001). Patients having 800 mL or greater of ANH had the most profound reduction in RBC transfusions (RRadj 0.57, p < 0.001). Platelet and plasma transfusions were also significantly lower with ANH. The ANH population had superior postoperative morbidity and mortality compared with the no ANH population. Conclusions. There is a significant association between ANH and reduced perioperative RBC transfusion in cardiac surgery. Transfusion reduction is most profound with larger volumes of ANH. Our findings suggest the volume of ANH, rather than just its use, may be an important feature of a center's blood conservation strategy. (C) 2015 by The Society of Thoracic Surgeons C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Michigan, Dept Cardiac Surg, Ann Arbor, MI 48109 USA. Specialty Care, Nashville, TN USA. St John Providence Hlth Syst Detroit Hosp, Detroit, MI USA. Henry Ford Hosp, Div Cardiac Surg, Detroit, MI 48202 USA. RP Likosky, DS (reprint author), Univ Michigan, Sch Med, Dept Cardiac Surg, Sect Hlth Serv Res & Qual, Ann Arbor, MI 48109 USA. EM likosky@med.umich.edu FU AHRQ HHS [R01 HS022535, R01HS022535, R03 HS022909, R03HS022909] NR 15 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD NOV PY 2015 VL 100 IS 5 BP 1581 EP 1587 DI 10.1016/j.athoracsur.2015.04.135 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CX6OM UT WOS:000365820400024 PM 26206721 ER PT J AU Paugh, TA Dickinson, TA Martin, JR Hanson, EC Fuller, J Heung, M Zhang, M Shann, KG Prager, RL Likosky, DS AF Paugh, Theron A. Dickinson, Timothy A. Martin, James R. Hanson, Eric C. Fuller, John Heung, Michael Zhang, Min Shann, Kenneth G. Prager, Richard L. Likosky, Donald S. CA Michigan Soc Thoracic Cardiovasc S PERForm Registry TI Impact of Ultrafiltration on Kidney Injury After Cardiac Surgery: The Michigan Experience SO ANNALS OF THORACIC SURGERY LA English DT Article ID CARDIOPULMONARY BYPASS; BLOOD CONSERVATION; HEMOFILTRATION; HEMATOCRIT; MORBIDITY; MORTALITY; OUTCOMES; RISK AB Background. This study examines the relationship between the use and volume of conventional ultrafiltration (CUF) and the risk of acute kidney injury (AKI) after isolated on-pump coronary artery bypass graft surgery. Methods. A total of 6,407 consecutive patients underwent isolated on-pump coronary artery bypass graft surgery between 2010 and 2013 at 21 medical centers participating in the PERFusion Measures and Outcomes (PERForm) registry. We assessed the effect of CUF use on AKI and other postoperative sequelae using a generalized linear mixed-effect model with a logit link. We also modeled the effect of increasing volume of CUF per weight on AKI, and tested for any modification by a patient's preoperative kidney function. Results. Patients having CUF were more likely to have diabetes, vascular disease, chronic obstructive pulmonary disease, congestive heart failure, history of a myocardial infarction, or an intraaortic balloon pump (p < 0.05). They had lower preoperative and nadir hematocrits, creatinine clearance, and ejection fraction (p < 0.05). Patients exposed to CUF had higher adjusted risk of AKI (adjusted odds ratio, 1.36; p = 0.002), although similar rates of death, stroke, and reoperation for bleeding (p > 0.05). The risk of AKI was modified by a patient's preoperative kidney function (p < 0.0004). Among patients with a creatinine clearance of less than 99.6 mL/min (95% confidence interval, 67.6 to 137.5), increasing volume of CUF was associated with a higher risk of AKI. Conclusions. Patients exposed to CUF had a higher adjusted risk of AKI. Clinical teams should consider lower volumes of CUF among patients with low creatinine clearance to minimize the risk of AKI. (C) 2015 by The Society of Thoracic Surgeons C1 Univ Michigan, Dept Cardiac Surg, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Specialty Care, Nashville, TN USA. St John Macomb Oakland Hosp, Warren, MI USA. William Beaumont Hosp, Troy, MI USA. St John Providence Hlth Syst Detroit Hosp, Detroit, MI USA. Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. RP Likosky, DS (reprint author), Univ Michigan, Sch Med, Sect Hlth Serv Res & Qual, Dept Cardiac Surg, Ann Arbor, MI 48109 USA. EM likosky@med.umich.edu NR 16 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD NOV PY 2015 VL 100 IS 5 BP 1683 EP 1688 DI 10.1016/j.athoracsur.2015.04.120 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CX6OM UT WOS:000365820400037 PM 26209495 ER PT J AU Thourani, VH Jensen, HA Babaliaros, V Suri, R Vemulapalli, S Dai, D Brennan, JM Rumsfeld, J Edwards, F Tuzcu, EM Svensson, L Szeto, WY Herrmann, H Kirtane, AJ Kodali, S Cohen, DJ Lerakis, S Devireddy, C Sarin, E Carroll, J Holmes, D Grover, FL Williams, M Maniar, H Shahian, D Mack, M AF Thourani, Vinod H. Jensen, Hanna A. Babaliaros, Vasilis Suri, Rakesh Vemulapalli, Sreekanth Dai, David Brennan, J. Matthew Rumsfeld, John Edwards, Fred Tuzcu, E. Murat Svensson, Lars Szeto, Wilson Y. Herrmann, Howard Kirtane, Ajay J. Kodali, Susheel Cohen, David J. Lerakis, Stamatios Devireddy, Chandan Sarin, Eric Carroll, John Holmes, David Grover, Frederick L. Williams, Mathew Maniar, Hersh Shahian, David Mack, Michael TI Transapical and Transaortic Transcatheter Aortic Valve Replacement in the United States SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 51st Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 24-28, 2015 CL San Diego, CA SP Soc Thorac Surg ID ACADEMIC RESEARCH CONSORTIUM; END-POINT DEFINITIONS; HIGH-RISK PATIENTS; CLINICAL-OUTCOMES; IMPLANTATION; STENOSIS; REGURGITATION; EXPERIENCE; MANAGEMENT; SURGERY AB Background. When transcatheter aortic valve replacement (TAVR) cannot be carried out through transfemoral access, alternative access TAVR is indicated. The purpose of this study was to explore inhospital and 1-year outcomes of patients undergoing alternative access TAVR through the transapical (TA) or transaortic (TAo) techniques in the United States. Methods. Clinical records of 4,953 patients undergoing TA (n = 4,085) or TAo (n = 868) TAVR from 2011 to 2014 in The Society of Thoracic Surgeons (STS)/American College of Cardiology Transcatheter Valve Therapy Registry were linked to Centers for Medicare and Medicaid Services hospital claims. Inhospital and 1-year clinical outcomes were stratified by operative risk; and the risk-adjusted association between access route and mortality, stroke, and heart failure repeat hospitalization was explored. Results. Mean age for all patients was 82.8 +/- 6.8 years. The median STS predicted risk of mortality was significantly higher among patients undergoing TAo (8.8 versus 7.4, p < 0.001). When compared with TA, TAo was associated with an increased risk of unadjusted 30-day mortality (10.3% versus 8.8%) and 1-year mortality (30.3% versus 25.6%, p = 0.006). There were no significant differences between TAo and TA for inhospital stroke rate (2.2%), major vascular complications (0.3%), and 1-year heart failure rehospitalizations (15.7%). Examination of high-risk and inoperable subgroups showed that 1-year mortality was significantly higher for TAo patients classified as inoperable (p = 0.012). Conclusions. Patients undergoing TAo TAVR are older, more likely female, and have significantly higher STS predicted risk of mortality scores than patients operated on by TA access. There were no risk-adjusted differences between TA and TAo access in mortality, stroke, or readmission rates as long as 1 year after TAVR. (C) 2015 by The Society of Thoracic Surgeons C1 Emory Univ, Atlanta, GA 30322 USA. Mayo Clin, Rochester, MN USA. Duke Univ, Sch Med, Durham, NC USA. Duke Clin Res Inst, Durham, NC USA. Univ Colorado, Sch Med, Aurora, CO USA. Denver VA Med Ctr, Denver, CO USA. Univ Florida, Jacksonville, FL USA. Cleveland Clin, Cleveland, OH 44106 USA. Univ Penn, Philadelphia, PA 19104 USA. Columbia Univ, New York, NY USA. Univ Missouri, Sch Med, St Lukes Mid Amer Heart Inst, Kansas City, MO 64108 USA. New York Univ Langone Med Ctr, New York, NY USA. Washington Univ, St Louis, MO USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Heart Hosp, Plano, TX USA. RP Thourani, VH (reprint author), Emory Midtown Hosp, 550 Peachtree St NE,Med Off Tower,6th Flr, Atlanta, GA 30308 USA. EM vthoura@emory.edu NR 31 TC 10 Z9 11 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD NOV PY 2015 VL 100 IS 5 BP 1718 EP 1727 DI 10.1016/j.athoracsur.2015.05.010 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CX6OM UT WOS:000365820400042 PM 26233276 ER PT J AU Wang, HF Wright, CD Wain, JC Ott, HC Mathisen, DJ AF Wang, Haifeng Wright, Cameron D. Wain, John C. Ott, Harald C. Mathisen, Douglas J. TI Idiopathic Subglottic Stenosis: Factors Affecting Outcome After Single-Stage Repair SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 51st Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 24-28, 2015 CL San Diego, CA SP Soc Thorac Surg ID LARYNGOTRACHEAL STENOSIS; TRACHEAL STENOSIS; RECONSTRUCTION; RESECTION AB Background. Idiopathic subglottic stenosis is a rare inflammatory condition affecting the subglottic larynx. We have treated 263 patients (only 2 were male) with this condition. The purpose of this study is to determine factors affecting outcome and predisposing to complications. Methods. Information was gathered from chart reviews, surveys, and a prospective database. Results. Median time from diagnosis to surgery was 24 months. Antinuclear antibodies when measured were positive in 76 patients (47%). Prior tracheal procedures were done in 58 patients (22%), and 184 patients (70%) had prior endoscopic procedures. Resection of the posterior cricoid mucosa with tracheal membranous wall flap was done in 150 patients (57%). Tailored cricoplasty was performed in 105 patients (40%). Extubation in the operating room was achieved in 247 patients (94%). Steroid therapy for edema was required in 63 patients (24%). Anastomotic complications occurred in 30 patients, 17 granulations and 7 subcutaneous air. Twenty-three patients (8.7%) have recurrence (14 mild, 9 recalcitrant) requiring dilation. Risk factors for anastomotic complications and recurrence were edema requiring steroids, use of mitomycin C, and prior tracheostomy, stents, and vocal cord involvement. Follow-up was available for 227 patients. Follow-up survey of 180 patients revealed, on a 10-point scale, effectiveness 9.4, satisfaction 9.4, and symptom improvement 9.4. A normal voice was present in 82 patients (45%); 96 patients (54%) had change in voice; and 121 patients (67%) had difficulty projecting their voice. Conclusions. Single-stage reconstructive surgery resulted in 96% good-to-excellent results. Recalcitrant stenosis developed in 4% of patients. Stents, post-operative edema, mitomycin use, and vocal cord involvement are risks for recurrence. Recurrence was related to reactivation of disease in 14 patients and to technical problems in 6 patients. (C) 2015 by The Society of Thoracic Surgeons C1 [Mathisen, Douglas J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Tongji Univ, Sch Med, Shanghai Pulm Hosp, Shanghai 200092, Peoples R China. RP Mathisen, DJ (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM dmathisen@partners.org NR 9 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD NOV PY 2015 VL 100 IS 5 BP 1804 EP 1811 DI 10.1016/j.athoracsur.2015.05.079 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CX6OM UT WOS:000365820400053 PM 26296271 ER PT J AU Tchantchaleishvili, V Lapar, DJ Odell, DD Stein, W Aftab, M Berfield, KS Eilers, AL Groth, SS Lazar, JF Robich, MP Shah, AA Smith, DA Stephens, EH Stock, CT DeNino, WF Nguyen, TC AF Tchantchaleishvili, Vakhtang LaPar, Damien J. Odell, David D. Stein, William Aftab, Muhammad Berfield, Kathleen S. Eilers, Amanda L. Groth, Shawn S. Lazar, John F. Robich, Michael P. Shah, Asad A. Smith, Danielle A. Stephens, Elizabeth H. Stock, Cameron T. DeNino, Walter F. Nguyen, Tom C. TI Predictors of Career Choice Among Cardiothoracic Surgery Trainees SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 51st Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 24-28, 2015 CL San Diego, CA SP Soc Thorac Surg ID RESIDENTS; PROGRAMS AB Background. The impact of factors influencing career choice by cardiothoracic surgery (CTS) trainees remains poorly defined in the modern era. We sought to examine the associations between CTS trainee characteristics and future career aspirations. Methods. The 2012 Thoracic Surgery In-Training Examination survey results were used to categorize responders according to career interest: congenital, adult cardiac, mixed cardiac/thoracic, and general thoracic surgery. Univariate and multivariable analyses were used to identify and analyze characteristics associated with career interest categories. Results. With a 100% response rate, 300 responses from trainees in programs accredited by the Accreditation Council for Graduate Medical Education were included in the analysis. Multinomial logistic regression identified three factors associated with career choice in CTS: level of training (p < 0.001), type of training pathway (p < 0.001), and primary motivating factor to pursue CTS (p = 0.002). Trainees interested in general thoracic surgery were more likely to commit to CTS during their senior years of general surgery training and were more likely to enroll in 2-year or 3-year traditional fellowships, whereas individuals pursuing adult or congenital cardiac surgery were more likely to commit earlier during training and were more commonly interested in 6-year integrated or joint training pathways. Moreover, trainees interested in general thoracic surgery were predominantly influenced by early mentorship (p = 0.025 vs adult cardiac), and trainees interested in adult cardiac surgery were more likely to be influenced by types of operations (p = 0.047 vs general thoracic). Conclusions. Career choice in CTS appears strongly associated with level of training, exposure to mentors, and training paradigm. These results demonstrate the importance of maintaining all four currently approved training pathways to retain balance and diversity in future CTS practices. (C) 2015 by The Society of Thoracic Surgeons C1 Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Univ Virginia, Charlottesville, VA USA. Univ Pittsburgh, Pittsburgh, PA USA. Emory Univ, Atlanta, GA 30322 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Washington, Seattle, WA 98195 USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. Baylor Coll Med, Houston, TX 77030 USA. Pinnacle Hlth Cardiovasc Inst, Harrisbsurg, PA USA. Duke Univ, Med Ctr, Durham, NC USA. Northwestern Univ, Chicago, IL 60611 USA. Columbia Univ, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Texas Houston, Sch Med, Mem Hermann Hosp, Inst Heart & Vasc, Houston, TX USA. RP Nguyen, TC (reprint author), Univ Texas Houston Mem Hermann, Houston, TX 77030 USA. EM tom.c.nguyen@gmail.com NR 14 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 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD NOV PY 2015 VL 100 IS 5 BP 1849 EP 1854 DI 10.1016/j.athoracsur.2015.04.073 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CX6OM UT WOS:000365820400059 PM 26163358 ER PT J AU Bhatt, DL Drozda, JP Shahian, DM Chan, PS Fonarow, GC Heidenreich, PA Jacobs, JP Masoudi, FA Peterson, ED Welke, KF AF Bhatt, Deepak L. Drozda, Joseph P., Jr. Shahian, David M. Chan, Paul S. Fonarow, Gregg C. Heidenreich, Paul A. Jacobs, Jeffrey P. Masoudi, Frederick A. Peterson, Eric D. Welke, Karl F. CA Writing Committee TI ACC/AHA/STS Statement on the Future of Registries and the Performance Measurement Enterprise: A Report of the American College of Cardiology/American Heart Association Task Force on Performance Measures and The Society of Thoracic Surgeons SO ANNALS OF THORACIC SURGERY LA English DT Article ID QUALITY-OF-CARE; ADULT CARDIAC-SURGERY; ACUTE MYOCARDIAL-INFARCTION; PERCUTANEOUS CORONARY INTERVENTION; BYPASS-GRAFTING SURGERY; CARDIOVASCULAR EVENT RATES; TRANSIENT ISCHEMIC ATTACK; HOSPITAL OUTCOMES; GUIDELINES-STROKE; SCIENTIFIC STATEMENT C1 [Bhatt, Deepak L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Cambridge, MA 02138 USA. [Drozda, Joseph P., Jr.] Mercy Hlth, Outcomes Res, Philadelphia, PA 19143 USA. [Shahian, David M.] Massachusetts Gen Hosp, Ctr Qual & Safety, Res, Boston, MA 02114 USA. [Chan, Paul S.] Mid Amer Heart Inst, Cardiol, Kansas City, MO 64111 USA. [Fonarow, Gregg C.] Ahmanson UCLA Cardiomyopathy Ctr, Div Cardiol, Los Angeles, CA USA. [Heidenreich, Paul A.] Stanford VA Palo Alto Hlth Care Syst, Med, Palo Alto, CA USA. [Masoudi, Frederick A.] Univ Colorado Denver, Med, Div Cardiol, Denver, CO USA. [Peterson, Eric D.] Duke Clin Res Inst, Med, Durham, NC USA. [Welke, Karl F.] Childrens Hosp Illinois, Peoria, IL USA. RP Bhatt, DL (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Cambridge, MA 02138 USA. NR 110 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD NOV PY 2015 VL 100 IS 5 BP 1926 EP 1941 DI 10.1016/j.athoracsur.2015.07.078 PG 16 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA CX6OM UT WOS:000365820400085 PM 26438978 ER PT J AU Boots, EA Schultz, SA Almeida, RP Oh, JM Koscik, RL Dowling, MN Gallagher, CL Carlsson, CM Rowley, HA Bendlin, BB Asthana, S Sager, MA Hermann, BP Johnson, SC Okonkwo, OC AF Boots, Elizabeth A. Schultz, Stephanie A. Almeida, Rodrigo P. Oh, Jennifer M. Koscik, Rebecca L. Dowling, Maritza N. Gallagher, Catherine L. Carlsson, Cynthia M. Rowley, Howard A. Bendlin, Barbara B. Asthana, Sanjay Sager, Mark A. Hermann, Bruce P. Johnson, Sterling C. Okonkwo, Ozioma C. TI Occupational Complexity and Cognitive Reserve in a Middle-Aged Cohort at Risk for Alzheimer's Disease SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE Alzheimer's disease; Occupation; Cognitive reserve; Hippocampus; Cognition; Imaging ID SURFACE-BASED ANALYSIS; PITTSBURGH COMPOUND-B; LIFETIME OCCUPATION; EMISSION-TOMOGRAPHY; WISCONSIN-REGISTRY; BRAIN VOLUME; EDUCATION; DECLINE; DEMENTIA; ADULTS AB Higher occupational attainment has previously been associated with increased Alzheimer's disease (AD) neuropathology when individuals are matched for cognitive function, indicating occupation could provide cognitive reserve. We examined whether occupational complexity (OCC) associates with decreased hippocampal volume and increased whole-brain atrophy given comparable cognitive function in middle-aged adults at risk for AD. Participants (n = 323) underwent structural MRI, cognitive evaluation, and work history assessment. Three complexity ratings (work with data, people, and things) were obtained, averaged across up to 3 reported jobs, weighted by years per job, and summed to create a composite OCC rating. Greater OCC was associated with decreased hippocampal volume and increased whole-brain atrophy when matched for cognitive function; results remained substantively unchanged after adjusting for several demographic, AD risk, vascular, mental health, and socioeconomic characteristics. These findings suggest that, in people at risk for AD, OCC may confer resilience to the adverse effects of neuropathology on cognition. C1 [Boots, Elizabeth A.; Schultz, Stephanie A.; Almeida, Rodrigo P.; Oh, Jennifer M.; Gallagher, Catherine L.; Carlsson, Cynthia M.; Bendlin, Barbara B.; Asthana, Sanjay; Johnson, Sterling C.; Okonkwo, Ozioma C.] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI 53705 USA. [Boots, Elizabeth A.; Schultz, Stephanie A.; Almeida, Rodrigo P.; Oh, Jennifer M.; Dowling, Maritza N.; Gallagher, Catherine L.; Carlsson, Cynthia M.; Rowley, Howard A.; Bendlin, Barbara B.; Asthana, Sanjay; Sager, Mark A.; Hermann, Bruce P.; Johnson, Sterling C.; Okonkwo, Ozioma C.] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Dis Res Ctr, Madison, WI 53792 USA. [Almeida, Rodrigo P.] Univ Fed Fluminense, BR-24220 Niteroi, RJ, Brazil. [Koscik, Rebecca L.; Bendlin, Barbara B.; Asthana, Sanjay; Sager, Mark A.; Hermann, Bruce P.; Johnson, Sterling C.; Okonkwo, Ozioma C.] Univ Wisconsin, Sch Med & Publ Hlth, Wisconsin Alzheimers Inst, Madison, WI 53705 USA. [Dowling, Maritza N.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Biostat & Med Informat, Madison, WI 53792 USA. [Gallagher, Catherine L.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Neurol, Madison, WI 53705 USA. [Rowley, Howard A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Radiol, Madison, WI 53792 USA. RP Okonkwo, OC (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI 53792 USA. EM ozioma@medicine.wisc.edu OI Schultz, Stephanie/0000-0001-8460-4415 FU NCATS NIH HHS [UL1 TR000427]; NCRR NIH HHS [UL1RR025011]; NIA NIH HHS [R01 AG037639, K23AG045957, P50 AG033514, P50 AG033514-S1, R01 AG021155, R01 AG027161] NR 40 TC 4 Z9 4 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 EI 1873-5843 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD NOV PY 2015 VL 30 IS 7 BP 634 EP 642 DI 10.1093/arclin/acv041 PG 9 WC Psychology, Clinical; Psychology SC Psychology GA CY4GQ UT WOS:000366367000005 PM 26156334 ER PT J AU Alegret, M Valero, S Ortega, G Espinosa, A Sanabria, A Hernandez, I Rodriguez, O Rosende-Roca, M Mauleon, A Vargas, L Martin, E Ruiz, A Tarraga, L Amariglio, RE Rentz, DM Boada, M AF Alegret, Montserrat Valero, Sergi Ortega, Gemma Espinosa, Ana Sanabria, Angela Hernandez, Isabel Rodriguez, Octavio Rosende-Roca, Maitee Mauleon, Ana Vargas, Liliana Martin, Elvira Ruiz, Agustin Tarraga, Lluis Amariglio, Rebecca E. Rentz, Dorene M. Boada, Merce TI Validation of the Spanish Version of the Face Name Associative Memory Exam (S-FNAME) in Cognitively Normal Older Individuals SO ARCHIVES OF CLINICAL NEUROPSYCHOLOGY LA English DT Article DE FNAME; Episodic memory; Preclinical Alzheimer's disease; Instrument validation ID MINI-MENTAL STATE; EDUCATION; DEMENTIA; AGE AB The Face Name Associative Memory Exam (FNAME) is a paired associative memory test that has demonstrated sensitivity to amyloid burden in cognitively normal individuals, a biomarker of preclinical Alzheimer's disease. Normative data adjusted for age were reported in American healthy individuals older than 57. We aimed to report the psychometric characteristics of a Spanish version ofFNAME(S-FNAME) when administered to Spanish-speaking people. We sought to investigate convergent validity of S-FNAME with another memory measure and to identify which demographic characteristics might be associated with performance on S-FNAME. We administered the S-FNAME to 110 literate, cognitively normal, Spanish individuals older than 49 years from the Memory Clinic Fundacio ACE. Construct validity of S-FNAME showed 2 components: face-name and face-occupation. A significant correlation between S-FNAME and Word List from the WMS-III supported convergent validity. The S-FNAME was also associated with age and gender. Thus, we provide normative data for age and gender. C1 [Alegret, Montserrat; Valero, Sergi; Ortega, Gemma; Espinosa, Ana; Sanabria, Angela; Hernandez, Isabel; Rodriguez, Octavio; Rosende-Roca, Maitee; Mauleon, Ana; Vargas, Liliana; Martin, Elvira; Ruiz, Agustin; Tarraga, Lluis; Boada, Merce] Fundacio ACE, Inst Catala Neurociencies Aplicades, Memory Clin, Barcelona, Spain. [Valero, Sergi] Univ Autonoma Barcelona, CIBERSAM, Hosp Univ Vall DHebron, Dept Psychiat, E-08193 Barcelona, Spain. [Amariglio, Rebecca E.; Rentz, Dorene M.] Brigham & Womens Hosp, Dept Neurol, Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA. [Amariglio, Rebecca E.; Rentz, Dorene M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Alegret, M (reprint author), Fundacio ACE, Inst Catala Neurociencies Aplicades, C Gran Via Carles 3,85 Bis, Barcelona 08028, Spain. EM malegret@fundacioace.com FU NIA NIH HHS [P50 AG005134] NR 25 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0887-6177 EI 1873-5843 J9 ARCH CLIN NEUROPSYCH JI Arch. Clin. Neuropsychol. PD NOV PY 2015 VL 30 IS 7 BP 712 EP 720 DI 10.1093/arclin/acv050 PG 9 WC Psychology, Clinical; Psychology SC Psychology GA CY4GQ UT WOS:000366367000011 PM 26289054 ER PT J AU Vaickus, LJ Wilbur, DC Sweeney, BJ Renshaw, AA AF Vaickus, Louis J. Wilbur, David C. Sweeney, Brenda J. Renshaw, Andrew A. TI Young Investigator Challenge: Comparison of 2 Different Methods of Manual Slide Screening in Semiautomated Gynecologic Cytology SO CANCER CYTOPATHOLOGY LA English DT Article DE full manual slide review; gynecologic oncology; human papillomavirus; manual screening; manual slide review; Papanicolaou (Pap) smear; quality assurance; semiautomated ID INCREASING CYTOTECHNOLOGIST WORKLOAD; PAPILLOMAVIRUS; CANCER AB BACKGROUND: Negative gynecologic cytology cases (ie, those diagnosed as negative for intraepithelial lesion or malignancy) are manually reviewed by 2 methods using semiautomated screening: 1) immediate full slide review (FSR) after fields-of-view analysis (FOV) (FOV 1 FSR), and 2) quality-assurance/high-risk, quintile-directed full manual review (FMR). Data supporting current guidelines were limited. The authors investigated FMR, FOV 1 FSR, and the review process in general. METHODS: Gynecologic cytology cases from 2009 to 2014 at Massachusetts General Hospital were analyzed. The data comprised 93,169 patients, 194,656 specimens, and 49,979 human papillomavirus (HPV) tests. RESULTS: In patients who underwent FMR, the epithelial cell abnormality (ECA) rate was correlated with the HPV-positive rate (correlation coefficient [r(2)] = 0.82; Y = 0.19X + 0.02), and both rates decreased with age. For patients who underwent FOV 1 FSR, the ECA rate was also related to the HPV-positive rate (r(2) + 0.86; Y = 0.39X + 0.11), and both rates decreased with age. The FMR group had similar HPV-positive rates compared to the FOV 1 FSR group (2%-52% vs 9%-68%, respectively). HPV-positive patients had a higher risk of ECA than HPV-negative patients (40% vs 8%; P < .0001). Currently, manual review allocates resources inefficiently, to older, HPV-negative patients as compared to younger, HPV-positive patients. Additionally, too many patients who have HPV-positive specimens with ECA proceed from primary screening to FMR. This imbalance can be observed in the slope of the line comparing the FMR ECA rate with the HPV-positive rate (which might serve as a surrogate marker for adequacy of FOV 1 FSR screening). Therefore, laboratories should try to reduce the number of HPV-positive cases that reach FMR. CONCLUSIONS: Current review procedures devote too few resources to younger patients. FMR should be assigned according to HPV status and age. The slope of the line comparing the FMR ECA rate with the FMR HPV-positive rate might be a useful surrogate marker of screening accuracy. (C) 2015 American Cancer Society. C1 [Vaickus, Louis J.; Sweeney, Brenda J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wilbur, David C.] Massachusetts Gen Hosp, Pathol Associates, Boston, MA 02114 USA. [Renshaw, Andrew A.] Baptist Hosp Miami, Dept Pathol, Miami, FL USA. RP Vaickus, LJ (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM lvaickus@mgh.harvard.edu NR 6 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X EI 1934-6638 J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD NOV PY 2015 VL 123 IS 11 BP 650 EP 658 DI 10.1002/cncy.21581 PG 9 WC Oncology; Pathology SC Oncology; Pathology GA CY6DP UT WOS:000366498300005 PM 26769586 ER PT J AU Lawrenson, K Iversen, ES Tyrer, J Weber, RP Concannon, P Hazelett, DJ Li, QY Marks, JR Berchuck, A Lee, JM Aben, KKH Anton-Culver, H Antonenkova, N Bandera, EV Bean, Y Beckmann, MW Bisogna, M Bjorge, L Bogdanova, N Brinton, LA Brooks-Wilson, A Bruinsma, F Butzow, R Campbell, IG Carty, K Chang-Claude, J Chenevix-Trench, G Chen, A Chen, ZH Cook, LS Cramer, DW Cunningham, JM Cybulski, C Plisiecka-Halasa, J Dennis, J Dicks, E Doherty, JA Dork, T du Bois, A Eccles, D Easton, DT Edwards, RP Eilber, U Ekici, AB Fasching, PA Fridley, BL Gao, YT Gentry-Maharaj, A Giles, GG Glasspool, R Goode, EL Goodman, MT Gronwald, J Harter, P Hasmad, HN Hein, A Heitz, F Hildebrandt, MAT Hillemanns, P Hogdall, E Hogdall, C Hosono, S Jakubowska, A Paul, J Jensen, A Karlan, BY Kjaer, SK Kelemen, LE Kellar, M Kelley, JL Kiemeney, LA Krakstad, C Lambrechts, D Lambrechts, S Le, ND Lee, AW Cannioto, R Leminen, A Lester, J Levine, DA Liang, D Lissowska, J Lu, KR Lubinski, J Lundvall, L Massuger, LFAG Matsuo, K McGuire, V McLaughlin, JR Nevanlinna, H McNeish, I Menon, U Modugno, F Moysich, KB Narod, SA Nedergaard, L Ness, RB Azmi, MAN Odunsi, K Olson, SH Orlow, I Orsulic, S Pearce, CL Pejovic, T Pelttari, LM Permuth-Wey, J Phelan, CM Pike, MC Poole, EM Ramus, SJ Risch, HA Rosen, B Rossing, MA Rothstein, JH Rudolph, A Runnebaum, IB Rzepecka, IK Salvesen, HB Budzilowska, A Sellers, TA Shu, XO Shvetsov, YB Siddiqui, N Sieh, W Song, HL Southey, MC Sucheston, L Tangen, IL Teo, SH Terry, KL Thompson, PJ Timorek, A Tworoger, SS Van Nieuwenhuysen, E Vergote, I Vierkant, RA Wang-Gohrke, S Walsh, C Wentzensen, N Whittemore, AS Wicklund, KG Wilkens, LR Woo, YL Wu, XF Wu, AH Yang, HN Zheng, W Ziogas, A Coetzee, GA Freedman, ML Monteiro, ANA Moes-Sosnowska, J Kupryjanczyk, J Pharoah, PD Gayther, SA Schildkraut, JM AF Lawrenson, Kate Iversen, Edwin S. Tyrer, Jonathan Weber, Rachel Palmieri Concannon, Patrick Hazelett, Dennis J. Li, Qiyuan Marks, Jeffrey R. Berchuck, Andrew Lee, Janet M. Aben, Katja K. H. Anton-Culver, Hoda Antonenkova, Natalia Bandera, Elisa V. Bean, Yukie Beckmann, Matthias W. Bisogna, Maria Bjorge, Line Bogdanova, Natalia Brinton, Louise A. Brooks-Wilson, Angela Bruinsma, Fiona Butzow, Ralf Campbell, Ian G. Carty, Karen Chang-Claude, Jenny Chenevix-Trench, Georgia Chen, Ann Chen, Zhihua Cook, Linda S. Cramer, Daniel W. Cunningham, Julie M. Cybulski, Cezary Plisiecka-Halasa, Joanna Dennis, Joe Dicks, Ed Doherty, Jennifer A. Doerk, Thilo du Bois, Andreas Eccles, Diana Easton, Douglas T. Edwards, Robert P. Eilber, Ursula Ekici, Arif B. Fasching, Peter A. Fridley, Brooke L. Gao, Yu-Tang Gentry-Maharaj, Aleksandra Giles, Graham G. Glasspool, Rosalind Goode, Ellen L. Goodman, Marc T. Gronwald, Jacek Harter, Philipp Hasmad, Hanis Nazihah Hein, Alexander Heitz, Florian Hildebrandt, Michelle A. T. Hillemanns, Peter Hogdall, Estrid Hogdall, Claus Hosono, Satoyo Jakubowska, Anna Paul, James Jensen, Allan Karlan, Beth Y. Kjaer, Susanne Kruger Kelemen, Linda E. Kellar, Melissa Kelley, Joseph L. Kiemeney, Lambertus A. Krakstad, Camilla Lambrechts, Diether Lambrechts, Sandrina Le, Nhu D. Lee, Alice W. Cannioto, Rikki Leminen, Arto Lester, Jenny Levine, Douglas A. Liang, Dong Lissowska, Jolanta Lu, Karen Lubinski, Jan Lundvall, Lene Massuger, Leon F. A. G. Matsuo, Keitaro McGuire, Valerie McLaughlin, John R. Nevanlinna, Heli McNeish, Iain Menon, Usha Modugno, Francesmary Moysich, Kirsten B. Narod, Steven A. Nedergaard, Lotte Ness, Roberta B. Azmi, Mat Adenan Noor Odunsi, Kunle Olson, Sara H. Orlow, Irene Orsulic, Sandra Pearce, Celeste L. Pejovic, Tanja Pelttari, Liisa M. Permuth-Wey, Jennifer Phelan, Catherine M. Pike, Malcolm C. Poole, Elizabeth M. Ramus, Susan J. Risch, Harvey A. Rosen, Barry Rossing, Mary Anne Rothstein, Joseph H. Rudolph, Anja Runnebaum, Ingo B. Rzepecka, Iwona K. Salvesen, Helga B. Budzilowska, Agnieszka Sellers, Thomas A. Shu, Xiao-Ou Shvetsov, Yurii B. Siddiqui, Nadeem Sieh, Weiva Song, Honglin Southey, Melissa C. Sucheston, Lara Tangen, Ingvild L. Teo, Soo-Hwang Terry, Kathryn L. Thompson, Pamela J. Timorek, Agnieszka Tworoger, Shelley S. Van Nieuwenhuysen, Els Vergote, Ignace Vierkant, Robert A. Wang-Gohrke, Shan Walsh, Christine Wentzensen, Nicolas Whittemore, Alice S. Wicklund, Kristine G. Wilkens, Lynne R. Woo, Yin-Ling Wu, Xifeng Wu, Anna H. Yang, Hannah Zheng, Wei Ziogas, Argyrios Coetzee, Gerhard A. Freedman, Matthew L. Monteiro, Alvaro N. A. Moes-Sosnowska, Joanna Kupryjanczyk, Jolanta Pharoah, Paul D. Gayther, Simon A. Schildkraut, Joellen M. CA Australian Canc Study Ovarian Canc Australian Ovarian Canc Study Grp TI Common variants at the CHEK2 gene locus and risk of epithelial ovarian cancer SO CARCINOGENESIS LA English DT Article ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; GERMLINE MUTATIONS; FALLOPIAN-TUBE; REPAIR GENES; DNA-DAMAGE; IN-VITRO; BREAST; BRCA1; CELLS AB Genome-wide association studies have identified 20 genomic regions associated with risk of epithelial ovarian cancer (EOC), but many additional risk variants may exist. Here, we evaluated associations between common genetic variants [single nucleotide polymorphisms (SNPs) and indels] in DNA repair genes and EOC risk. We genotyped 2896 common variants at 143 gene loci in DNA samples from 15 397 patients with invasive EOC and controls. We found evidence of associations with EOC risk for variants at FANCA, EXO1, E2F4, E2F2, CREB5 and CHEK2 genes (P = 0.001). The strongest risk association was for CHEK2 SNP rs17507066 with serous EOC (P = 4.74 x 10(-7)). Additional genotyping and imputation of genotypes from the 1000 genomes project identified a slightly more significant association for CHEK2 SNP rs6005807 (r(2) with rs17507066 = 0.84, odds ratio (OR) 1.17, 95% CI 1.11-1.24, P = 1.1 x 10(-7)). We identified 293 variants in the region with likelihood ratios of less than 1: 100 for representing the causal variant. Functional annotation identified 25 candidate SNPs that alter transcription factor binding sites within regulatory elements active in EOC precursor tissues. In The Cancer Genome Atlas dataset, CHEK2 gene expression was significantly higher in primary EOCs compared to normal fallopian tube tissues (P = 3.72 x 10(-8)). We also identified an association between genotypes of the candidate causal SNP rs12166475 (r(2) = 0.99 with rs6005807) and CHEK2 expression (P = 2.70 x 10(-8)). These data suggest that common variants at 22q12.1 are associated with risk of serous EOC and CHEK2 as a plausible target susceptibility gene. C1 [Lee, Janet M.; Lee, Alice W.; Ramus, Susan J.; Wu, Anna H.] Univ So Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Iversen, Edwin S.; Anton-Culver, Hoda; Pike, Malcolm C.] Duke Univ, Dept Stat Sci, Durham, NC 27708 USA. [Tyrer, Jonathan; Song, Honglin; Pharoah, Paul D.] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Dept Oncol, Cambridge CB2 1TN, England. [Weber, Rachel Palmieri; Schildkraut, Joellen M.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. [Concannon, Patrick; du Bois, Andreas] Univ Florida, Genet Inst, Gainesville, FL 32611 USA. [Concannon, Patrick; du Bois, Andreas] Univ Florida, Dept Pathol Immunol & Lab Med, Gainesville, FL 32611 USA. [Hazelett, Dennis J.; Coetzee, Gerhard A.] Univ So Calif, Keck Sch Med, Norris Canc Ctr, Dept Urol, Los Angeles, CA 90089 USA. [Hazelett, Dennis J.; Coetzee, Gerhard A.] Univ So Calif, Keck Sch Med, Norris Canc Ctr, Dept Prevent Med, Los Angeles, CA 90089 USA. [Li, Qiyuan] Xiamen Univ, Sch Med, Xiamen 361000, Peoples R China. [Marks, Jeffrey R.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Berchuck, Andrew] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. [Aben, Katja K. H.] Dept Hlth Evidence, NL-6500 HB Nijmegen, Netherlands. [Aben, Katja K. H.; Ziogas, Argyrios] Ctr Comprehens Canc, NL-3542 EG Utrecht, Netherlands. [Anton-Culver, Hoda] Univ Calif Irvine, Sch Med, Genet Epidemiol Res Inst, Dept Epidemiol, Irvine, CA 92697 USA. [Antonenkova, Natalia] Byelorussian Inst Oncol & Med Radiol Aleksandrov, Minsk 223052, Byelarus. [Australian Canc Study Ovarian Canc] QIMR Berghofer Med Res Inst, Canc Div, Brisbane, Qld 4006, Australia. [Australian Ovarian Canc Study Grp] Peter MacCallum Canc Inst, East Melbourne, Vic 3002, Australia. [Bandera, Elisa V.] Rutgers Canc Inst New Jersey, Canc Prevent & Control, New Brunswick, NJ 08903 USA. [Bean, Yukie; Kellar, Melissa; Pejovic, Tanja] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97239 USA. [Bean, Yukie; Pejovic, Tanja] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA. [Beckmann, Matthias W.; Fasching, Peter A.; Hein, Alexander] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Comprehens Canc Ctr Erlangen EMN, Dept Gynecol & Obstet, D-91054 Erlangen, Germany. [Bisogna, Maria; Levine, Douglas A.] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10065 USA. [Bjorge, Line; Krakstad, Camilla; Salvesen, Helga B.; Tangen, Ingvild L.] Haukeland Hosp, Dept Gynecol & Obstet, N-5021 Bergen, Norway. [Bjorge, Line; Krakstad, Camilla; Salvesen, Helga B.; Tangen, Ingvild L.] Univ Bergen, Ctr Canc Biomarkers, Dept Clin Sci, N-5020 Bergen, Norway. [Bogdanova, Natalia; Doerk, Thilo] Hannover Med Sch, Gynaecol Res Unit, D-30625 Hannover, Germany. [Brinton, Louise A.; Wentzensen, Nicolas; Yang, Hannah] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20852 USA. [Brooks-Wilson, Angela] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada. [Brooks-Wilson, Angela] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada. [Bruinsma, Fiona; Giles, Graham G.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3004, Australia. [Butzow, Ralf; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M.] Univ Helsinki, Dept Obstet & Gynecol, Helsinki 00029, Finland. [Butzow, Ralf; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M.] Univ Helsinki, Cent Hosp, Helsinki 00029, Finland. [Butzow, Ralf] Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki 00029, Finland. [Campbell, Ian G.] Peter MacCallum Canc Ctr, Div Res, Canc Genet Lab, Melbourne, Vic 8006, Australia. [Campbell, Ian G.; Southey, Melissa C.] Univ Melbourne, Dept Pathol, Parkville, Vic 3002, Australia. [Campbell, Ian G.; Paul, James] Univ Melbourne, Dept Oncol, Sir Peter MacCallum Dept Oncol, Parkville, Vic 3002, Australia. Beatson West Scotland Canc Ctr, Canc Res UK Clin Trials Unit, Glasgow G12 0YN, Lanark, Scotland. [Chang-Claude, Jenny; Eilber, Ursula; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, D-69009 Heidelberg, Germany. [Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Canc Div, Brisbane, Qld 4029, Australia. [Chen, Ann; Chen, Zhihua] H Lee Moffitt Canc Ctr & Res Inst, Dept Biostat, Tampa, FL 33612 USA. [Cook, Linda S.] Univ New Mexico, Dept Internal Med, Div Epidemiol & Biostat, Albuquerque, NM 87131 USA. [Cramer, Daniel W.; Terry, Kathryn L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Cramer, Daniel W.; Terry, Kathryn L.] Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. [Cramer, Daniel W.; Terry, Kathryn L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Cunningham, Julie M.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. Pomeranian Med Univ, Dept Genet & Pathol, PL-70115 Szczecin, Poland. [Plisiecka-Halasa, Joanna; Lissowska, Jolanta; Budzilowska, Agnieszka; Moes-Sosnowska, Joanna; Kupryjanczyk, Jolanta] Maria Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, PL-02781 Warsaw, Poland. [Plisiecka-Halasa, Joanna; Lissowska, Jolanta; Budzilowska, Agnieszka; Moes-Sosnowska, Joanna; Kupryjanczyk, Jolanta] Inst Oncol, PL-02781 Warsaw, Poland. [Dennis, Joe; Dicks, Ed; Easton, Douglas T.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England. [Doherty, Jennifer A.] Geisel Sch Med Dartmouth, Sect Biostat & Epidemiol, Dept Community & Family Med, Lebanon, NH 03756 USA. [Harter, Philipp; Heitz, Florian] Kliniken Essen Mitte, Dept Gynecol & Gynecol Oncol, D-45136 Essen, Germany. [du Bois, Andreas; Harter, Philipp; Heitz, Florian] Dr Horst Schmidt Kliniken Wiesbaden, Dept Gynecol & Gynecol Oncol, D-65199 Wiesbaden, Germany. [Eccles, Diana; Edwards, Robert P.] Princess Anne Hosp, Wessex Clin Genet Serv, Southampton SO16 5YA, Hants, England. [Edwards, Robert P.; Cannioto, Rikki; Modugno, Francesmary] Univ Pittsburgh, Ovarian Canc Ctr Excellence, Pittsburgh, PA 15222 USA. [Ekici, Arif B.] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Inst Human Genet, D-91054 Erlangen, Germany. [Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol & Oncol, Dept Med, Los Angeles, CA 90095 USA. [Fridley, Brooke L.] Univ Kansas, Med Ctr, Biostat & Informat Shared Resource, Kansas City, KS 66160 USA. [Gao, Yu-Tang] Shanghai Canc Inst, Shanghai 200032, Peoples R China. [Gentry-Maharaj, Aleksandra; Menon, Usha] UCL, Inst Womens Hlth, Dept Womens Canc, London W1T 7DN, England. [Giles, Graham G.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic 3010, Australia. [Goode, Ellen L.; Vierkant, Robert A.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [Goodman, Marc T.; Thompson, Pamela J.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Canc Prevent & Control, Los Angeles, CA 90048 USA. [Goodman, Marc T.; Thompson, Pamela J.] Cedars Sinai Med Ctr, Community & Populat Hlth Res Inst, Dept Biomed Sci, Los Angeles, CA 90048 USA. [Hasmad, Hanis Nazihah] Canc Res Initiat Fdn, Sime Darby Med Ctr, Subang Jaya 47500, Malaysia. [Hildebrandt, Michelle A. T.; Teo, Soo-Hwang; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Hillemanns, Peter] Hannover Med Sch, Dept Obstet, D-30625 Hannover, Germany. [Hillemanns, Peter] Hannover Med Sch, Dept Gynaecol, D-30625 Hannover, Germany. [Hogdall, Estrid] Danish Canc Soc, Inst Canc Epidemiol, DK-2100 Copenhagen, Denmark. [Hogdall, Estrid] Univ Copenhagen, Herlev Hosp, Dept Pathol, Mol Unit, DK-2100 Copenhagen, Denmark. Univ Copenhagen, Rigshosp, Gyn Clin, DK-2100 Copenhagen, Denmark. [Hosono, Satoyo] Aichi Canc Ctr Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi 4648681, Japan. [Jensen, Allan; Kjaer, Susanne Kruger] Danish Canc Soc Res Ctr, Dept Virus Lifestyle & Genes, DK-2100 Copenhagen, Denmark. [Karlan, Beth Y.; Lester, Jenny; Orsulic, Sandra; Walsh, Christine] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA. [Kjaer, Susanne Kruger] Univ Copenhagen, Rigshosp, Dept Gynecol, DK-2100 Copenhagen, Denmark. [Kelemen, Linda E.; Kellar, Melissa] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC USA. [Kelley, Joseph L.] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15222 USA. [Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Hlth Evidence, NL-6500 HB Nijmegen, Netherlands. [Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6500 HB Nijmegen, Netherlands. [Lambrechts, Diether] VIB, Vesalius Res Ctr, B-3000 Leuven, Belgium. [Lambrechts, Diether] Univ Leuven, Dept Oncol, Lab Translat Genet, B-3000 Louvain, Belgium. [Lambrechts, Sandrina; Van Nieuwenhuysen, Els; Vergote, Ignace] Univ Hosp Leuven, Dept Oncol, Div Gynecol Oncol, B-3000 Louvain, Belgium. [Le, Nhu D.] BC Canc Agcy, Canc Control Res, Vancouver, BC V5Z 1L3, Canada. [Moysich, Kirsten B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [Liang, Dong; Sucheston, Lara] Texas So Univ, Coll Pharm & Hlth Sci, Houston, TX 77004 USA. [Lu, Karen] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. [Massuger, Leon F. A. G.] Radboud Univ Nijmegen, Med Ctr, Dept Gynaecol, NL-6500 HB Nijmegen, Netherlands. [Matsuo, Keitaro] Kyushu Univ, Fac Med Sci, Dept Prevent Med, Fukuoka 8128582, Japan. [McGuire, Valerie; Rothstein, Joseph H.; Sieh, Weiva; Whittemore, Alice S.] Stanford Univ, Sch Med, Dept Hlth Res & Policy Epidemiol, Stanford, CA 94305 USA. [McLaughlin, John R.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada. [McNeish, Iain] Univ Glasgow, Wolfson Wohl Canc Res Ctr, Beatson Inst Canc Res, Inst Canc Sci, Glasgow G61 1QH, Lanark, Scotland. [Modugno, Francesmary] Magee Womens Res Inst, Womens Canc Res Program, Pittsburgh, PA 15222 USA. [Modugno, Francesmary] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15222 USA. [Modugno, Francesmary] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15222 USA. [Modugno, Francesmary] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15222 USA. [Narod, Steven A.] Womens Coll Res Inst, Toronto, ON M5G 1N8, Canada. [Nedergaard, Lotte] Univ Copenhagen, Rigshosp, Dept Pathol, DK-2100 Copenhagen, Denmark. [Ness, Roberta B.] Univ Texas Houston, Sch Publ Hlth, Houston, TX 77225 USA. [Azmi, Mat Adenan Noor; Woo, Yin-Ling] Univ Malaya, Med Ctr, Dept Obstet & Gynaecol, Kuala Lumpur 50603, Malaysia. [Odunsi, Kunle] Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA. [Olson, Sara H.; Orlow, Irene; Pike, Malcolm C.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA. [Pearce, Celeste L.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Permuth-Wey, Jennifer; Phelan, Catherine M.; Sellers, Thomas A.] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL 33612 USA. [Poole, Elizabeth M.; Tworoger, Shelley S.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA. [Poole, Elizabeth M.; Tworoger, Shelley S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Poole, Elizabeth M.; Tworoger, Shelley S.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Risch, Harvey A.] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT 06520 USA. [Rosen, Barry] Princess Margaret Hosp, Dept Gynecol Oncol, Toronto, ON M5G 1X6, Canada. [Rosen, Barry] Univ Toronto, Fac Med, Dept Obstet & Gynecol, Toronto, ON M5G 1X6, Canada. [Rossing, Mary Anne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98109 USA. [Rossing, Mary Anne; Wicklund, Kristine G.] Univ Washington, Dept Epidemiol, Seattle, WA 98109 USA. [Runnebaum, Ingo B.] Univ Jena, Jena Univ Hosp, Dept Gynaecol, D-07743 Jena, Germany. [Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Sch Med, Div Epidemiol, Dept Med,Vanderbilt Epidemiol Ctr, Nashville, TN 37203 USA. [Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37203 USA. [Shvetsov, Yurii B.; Wilkens, Lynne R.] Univ Hawaii, Ctr Canc, Canc Epidemiol Program, Honolulu, HI 96826 USA. [Siddiqui, Nadeem] Glasgow Royal Infirm, Dept Gynaecol Oncol, Glasgow G4 0SF, Lanark, Scotland. [Teo, Soo-Hwang; Woo, Yin-Ling] Univ Malaya, Canc Res Inst, Fac Med, Med Ctr, Kuala Lumpur 50603, Malaysia. [Timorek, Agnieszka] Med Univ Warsaw, IInd Fac Med, Dept Obstet Gynecol & Oncol, PL-03242 Warsaw, Poland. [Timorek, Agnieszka] Brodnowski Hosp, PL-03242 Warsaw, Poland. [Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynecol, D-89075 Ulm, Germany. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Monteiro, Alvaro N. A.] H Lee Moffitt Canc Ctr & Res Inst, Div Populat Sci, Canc Epidemiol Program, Tampa, FL 33612 USA. [Monteiro, Alvaro N. A.] Res Inst, Tampa, FL 33612 USA. [Schildkraut, Joellen M.] Duke Canc Inst, Canc Control & Populat Sci, Durham, NC 27710 USA. RP Schildkraut, JM (reprint author), Duke Canc Inst, Canc Control & Populat Sci, Durham, NC 27710 USA. EM jms2yf@virginia.edu RI U-ID, Kyushu/C-5291-2016; Teo, Soo-hwang/H-2353-2014; Hein, Alexander/F-6999-2010; Bandera, Elisa/M-4169-2014; Brooks-Wilson, Angela/E-9399-2012; Aben, Katja/G-9686-2016; Bowtell, David/H-1007-2016; Dork, Thilo/J-8620-2012; Gronwald, Jacek/A-4576-2017; Bjorge, Line/C-1307-2017; salvesen, Helga/C-1187-2017; OI Orlow, Irene/0000-0001-6234-6961; Krakstad, Camilla/0000-0002-0174-8139; Hein, Alexander/0000-0003-2601-3398; Bandera, Elisa/0000-0002-8789-2755; Brooks-Wilson, Angela/0000-0003-1009-6408; Aben, Katja/0000-0002-0214-2147; Bowtell, David/0000-0001-9089-7525; Gronwald, Jacek/0000-0002-3643-2871; Bjorge, Line/0000-0002-0240-2770; salvesen, Helga/0000-0002-4438-8831; Glasspool, Rosalind/0000-0002-5000-1680 FU Genetic Associations and Mechanisms in Oncology (GAME-ON): a NCI Cancer Post-GWAS Initiative [U19-CA148112]; COGS project through a European Commission's Seventh Framework Programme grant [223175-HEALTH-F2-2009-223175]; Ovarian Cancer Research Fund [PPD/RPCI.07]; Department of Defense Award [W81XWH-12-1-0561, W81XWH-07-0449]; National Institutes of Health [K07-CA080668, K07-CA095666, K07-CA143047, K22-CA138563]; Department of Defense [W81XWH-12-1-0561, DAMD17-02-1-0666, DAMD17-02-1-0669, W81XWH-10-1-02802]; California Cancer Research Program [00-01389V-20170, 2II0200]; Cancer Prevention Institute of California; Fred C. and Katherine B. Andersen Foundation; Lon V Smith Foundation [LVS-39420]; Mayo Foundation; Minnesota Ovarian Cancer Alliance; National Center for Research Resources/General Clinical Research Center [M01-RR000056, N01-CN025403, N01-CN55424, N01-PC67001, N01-PC67010, P01-CA17054, P30-CA14089, P30-CA15083, P30-CA072720, P50-CA105009, P50-CA136393, P50-CA159981, R01-CA058860, R01-CA074850, R01-CA080742, R01-CA092044, R01-CA112523, R01-CA122443, R01-CA126841, R01-CA16056]; Rutgers Cancer Institute of New Jersey; US Public Health Service [PSA-042205]; National Cancer Institute [1K99CA184415-01]; National Health and Medical Research Council; National Center for Advancing Translational Sciences (NCATS) [UL1TR000124]; National Center for Research Resources / General Clinical Research Center [R01-CA54419, R01-CA58598, R01-CA61132, R01-CA76016, R01-CA83918, R01-CA87538, R01-CA95023, R01-CA063678, R01 CA114343, R03-CA113148, R03-CA115195, U01-CA69417, U01-CA71966, UM1-CA182910] FX The scientific development and funding for this project were supported by the following: the Genetic Associations and Mechanisms in Oncology (GAME-ON): a NCI Cancer Post-GWAS Initiative (U19-CA148112); the COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175-HEALTH-F2-2009-223175); the Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07); and Department of Defense Award (W81XWH-12-1-0561, W81XWH-07-0449). F.M. was supported by National Institutes of Health K07-CA080668; S.S.T. and E.M.P. were supported in part by Department of Defense Award W81XWH-12-1-0561. Funding of the constituent studies was provided by: California Cancer Research Program (00-01389V-20170, 2II0200); Cancer Prevention Institute of California; Department of Defense (DAMD17-02-1-0666, DAMD17-02-1-0669, W81XWH-10-1-02802); Fred C. and Katherine B. Andersen Foundation; Lon V Smith Foundation grant LVS-39420; Mayo Foundation; Minnesota Ovarian Cancer Alliance; National Institutes of Health (K07-CA095666, K07-CA143047, K22-CA138563); National Center for Research Resources/General Clinical Research Center grant M01-RR000056, N01-CN025403, N01-CN55424, N01-PC67001, N01-PC67010, P01-CA17054, P30-CA14089, P30-CA15083, P30-CA072720, P50-CA105009, P50-CA136393, P50-CA159981, R01-CA058860, R01-CA074850, R01-CA080742, R01-CA092044, R01-CA112523, R01-CA122443, R01-CA126841, R01-CA16056, R01-CA54419, R01-CA58598, R01-CA61132, R01-CA76016, R01-CA83918, R01-CA87538, R01-CA95023, R01-CA063678, R01 CA114343, R03-CA113148, R03-CA115195, U01-CA69417, U01-CA71966), UM1-CA182910; Rutgers Cancer Institute of New Jersey; and the US Public Health Service (PSA-042205). Personal support: K.L is supported by a K99/R00 grant from the National Cancer Institute (Grant number 1K99CA184415-01). D.F.E. is a Principal Research Fellow of Cancer Research UK. G.C.-T. and P.M.W. are supported by the National Health and Medical Research Council. B.K. holds an American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124. NR 51 TC 5 Z9 5 U1 2 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 2015 VL 36 IS 11 BP 1341 EP 1353 DI 10.1093/carcin/bgv138 PG 13 WC Oncology SC Oncology GA CY4OF UT WOS:000366386800011 PM 26424751 ER PT J AU Flowers, CR Brown, JR Rosenthal, H Stock, W Katzen, HI Cohen, JB Sinha, R Lakhanpal, S Leis, JF Waller, EK Jaye, DL AF Flowers, Christopher R. Brown, Jennifer R. Rosenthal, Hilary Stock, Wendy Katzen, Harvey I. Cohen, Jonathon B. Sinha, Rajni Lakhanpal, Shailendra Leis, Jose F. Waller, Edmund K. Jaye, David L. TI A Phase 2 Trial of Fludarabine Combined With Subcutaneous Alemtuzumab for the Treatment of Relapsed/Refractory B-Cell Chronic Lymphocytic Leukemia SO CLINICAL LYMPHOMA MYELOMA & LEUKEMIA LA English DT Article DE Alemtuzumab; Chronic lymphocytic leukemia; Fludarabine; Minimal residual disease; Small lymphocytic lymphoma ID THERAPY; CYCLOPHOSPHAMIDE; RITUXIMAB AB We evaluated alemtuzumab in combination with fludarabine for patients with relapsed chronic lymphocytic leukemia. Sixty patients were enrolled onto this phase 2 study; the complete response rate was 8.3%, with an overall response rate of 28.3%. Although many patients developed cytomegalovirus reactivation, these episodes were manageable. This regimen should be considered only for fit patients refractory to available therapies. Background: Alemtuzumab is effective in fludarabine-refractory patients with chronic lymphocytic leukemia. We performed a phase 2 study of alemtuzumab in combination with fludarabine in patients with relapsed disease. Patients and Methods: Patients received alemtuzumab and fludarabine daily on days 1 to 5 of a 28-day cycle for up to 6 cycles with the primary objective of determining the rate of complete response. Of 60 enrolled patients, 51 had previously received fludarabine, and 60% had received 3 or more prior therapies. Results: Five patients experienced complete response (8.3%) and 12 experienced partial response, yielding an overall response rate of 28.3% for the intention-to-treat population. Among the 41 patients who completed at least 4 cycles of therapy, the complete response rate was 20%. Median progression-free survival was 211 days. Forty-seven percent of patients experienced cytomegalovirus viremia, including 4 patients with symptomatic cytomegalovirus disease. All patients responded to antiviral therapy. Conclusion: Despite some evidence of efficacy in this setting, the primary end point for the study was not met. In the era of targeted agents that are well tolerated, the combination of fludarabine and alemtuzumab should be used rarely for a select group of fit patients who are refractory to standard therapies. C1 [Flowers, Christopher R.; Rosenthal, Hilary; Cohen, Jonathon B.; Sinha, Rajni; Waller, Edmund K.; Jaye, David L.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Stock, Wendy] Univ Chicago, Med Ctr & Hosp, Chicago, IL 60637 USA. [Katzen, Harvey I.] Oncol Hematol Associates, Clinton, MD USA. [Lakhanpal, Shailendra] Birmingham Hematol & Oncol Associates LLC, Birmingham, AL USA. [Leis, Jose F.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Flowers, CR (reprint author), Emory Univ, Winship Canc Inst, 1365 Clifton Rd NE,Suite B4300, Atlanta, GA 30322 USA. EM crflowe@emory.edu RI Flowers, Christopher/F-1953-2010 OI Flowers, Christopher/0000-0002-9524-3990 FU Berlex FX Support for the conduct of this study was provided by Berlex. NR 17 TC 0 Z9 1 U1 0 U2 1 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 2152-2650 EI 2152-2669 J9 CL LYMPH MYELOM LEUK JI Clin. Lymphoma Myeloma Leuk. PD NOV PY 2015 VL 15 IS 11 BP 694 EP 698 DI 10.1016/j.clml.2015.07.640 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA CY1EA UT WOS:000366148300009 PM 26385641 ER PT J AU Walker, RJ Smalls, BL Egede, LE AF Walker, Rebekah J. Smalls, Brittany L. Egede, Leonard E. TI Social determinants of health in adults with type 2 diabetes-Contribution of mutable and immutable factors SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE Diabetes; Social determinants; Socioeconomic; Psychological; Built environment ID OF-THE-LITERATURE; GLYCEMIC CONTROL; SELF-CARE; PSYCHOMETRIC PROPERTIES; PSYCHOLOGICAL DISTRESS; SOCIOECONOMIC POSITION; MEDICATION ADHERENCE; DEPRESSION; MANAGEMENT; METAANALYSIS AB Aims: Socioeconomic, psychosocial, and neighborhood factors influence clinical outcomes and self-care behaviors in diabetes; however, few studies simultaneously assessed the impact of multiple social determinant of health factors on glycemic control. We used an explanatory model to examine the differential contribution of social determinants and clinical factors on glycemic control. Secondarily, we examined the contribution of mutable and immutable factors to identify meaningful future interventions. Methods: Six hundred and fifteen adults with type 2 diabetes in the southeastern United States were recruited. A hierarchical model was run with HbA1c as the dependent variable and independent variables entered in blocks: demographics (block 1), socioeconomic (block 2), psychosocial (block 3), built environment (block 4), clinical (block 5), and knowledge/selfcare (block 6). Results: Significant associations for HbA1c included self-efficacy (beta = -0.10, p < 0.001), social support (beta = 0.01, p < 0.05), comorbidity (beta = -0.09, p < 0.05), insulin use (beta = 0.95, p < 0.001), medication adherence (beta = -0.11, p < 0.05), and being a former smoker (beta = 0.34, p < 0.05); accounting for 24.4% of the variance. Conclusions: Important factors that drive glycemic control are mutable, and amenable to health interventions. Greater attention should be given to interventions that increase self-efficacy and social support, reduce the burden of comorbidities, and enhance medication adherence and smoking cessation. (C) 2015 Elsevier Ireland Ltd. All rights reserved. C1 [Walker, Rebekah J.; Egede, Leonard E.] Ralph H Johnson VAMC, Charleston VA HSR&D COIN, Hlth Equ & Rural Outreach Innovat Ctr HEROIC, Charleston, SC USA. [Walker, Rebekah J.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. [Smalls, Brittany L.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Egede, Leonard E.] Med Univ S Carolina, Dept Med, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280,POB 250593, Charleston, SC 29425 USA. EM egedel@musc.edu FU National Institute of Diabetes and Digestive and Kidney Disease [K24DK093699-01] FX This study was supported by Grant K24DK093699-01 from The National Institute of Diabetes and Digestive and Kidney Disease (PI: Leonard Egede). NR 48 TC 1 Z9 1 U1 11 U2 21 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8227 EI 1872-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD NOV PY 2015 VL 110 IS 2 BP 193 EP 201 DI 10.1016/j.diabres.2015.09.007 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA CY3NS UT WOS:000366317100011 PM 26411692 ER PT J AU Huang, RY Wei, YY Hung, RJ Liu, G Su, L Zhang, RY Zong, XC Zhang, ZF Morgenstern, H Bruske, I Heinrich, J Hong, YC Kim, JH Cote, M Wenzlaff, A Schwartz, AG Stucker, I Mclaughlin, LJ Marcus, MW Davies, MPA Liloglou, T Field, JK Matsuo, K Barnett, M Thornquist, M Goodman, G Wang, Y Chen, SZ Yang, P Duell, EJ Andrew, AS Lazarus, P Muscat, J Woll, P Horsman, J Teare, MD Flugelman, A Rennert, G Zhang, Y Brenner, H Stegmaier, C van der Heijden, EHFM Aben, K Kiemeney, L Barros-Dios, J Perez-Rios, M Ruano-Ravina, A Caporaso, NE Bertazzi, PA Landi, MT Dai, JC Shen, HB Fernandez-Tardon, G Rodriguez-Suarez, M Tardon, A Christiani, DC AF Huang, Ruyi Wei, Yongyue Hung, Rayjean J. Liu, Geoffrey Su, Li Zhang, Ruyang Zong, Xuchen Zhang, Zuo-Feng Morgenstern, Hal Brueske, Irene Heinrich, Joachim Hong, Yun-Chul Kim, Jin Hee Cote, Michele Wenzlaff, Angela Schwartz, Ann G. Stucker, Isabelle Mclaughlin, L. John Marcus, Michael W. Davies, Michael P. A. Liloglou, Triantafillos Field, John K. Matsuo, Keitaro Barnett, Matt Thornquist, Mark Goodman, Gary Wang, Yi Chen, Size Yang, Ping Duell, Eric J. Andrew, Angeline S. Lazarus, Philip Muscat, Joshua Woll, Penella Horsman, Janet Teare, M. Dawn Flugelman, Anath Rennert, Gad Zhang, Yan Brenner, Hermann Stegmaier, Christa van der Heijden, Erik H. F. M. Aben, Katja Kiemeney, Lambertus Barros-Dios, Juan Perez-Rios, Monica Ruano-Ravina, Alberto Caporaso, Neil E. Bertazzi, Pier Alberto Landi, Maria Teresa Dai, Juncheng Shen, Hongbing Fernandez-Tardon, Guillermo Rodriguez-Suarez, Marta Tardon, Adonina Christiani, David C. TI Associated Links Among Smoking, Chronic Obstructive Pulmonary Disease, and Small Cell Lung Cancer: A Pooled Analysis in the International Lung Cancer Consortium SO EBIOMEDICINE LA English DT Article DE Smoking behaviors; Chronic obstructive pulmonary disease; Small cell lung cancer risk; Multicenter pooling; Causal mediation analysis ID GENETIC SUSCEPTIBILITY; RESIDENTIAL RADON; HEAVY SMOKERS; DNA-REPAIR; RISK; POPULATION; COPD; COHORT; VARIANTS; HEALTH AB Background: The high relapse and mortality rate of small-cell lung cancer (SCLC) fuels the need for epidemiologic study to aid in its prevention. Methods: We included 24 studies from the ILCCO collaboration. Random-effects panel logistic regression and cubic spline regression were used to estimate the effects of smoking behaviors on SCLC risk and explore their non-linearity. Further, we explored whether the risk of smoking on SCLC was mediated through COPD. Findings: Significant dose-response relationships of SCLC risk were observed for all quantitative smoking variables. Smoking pack-years were associated with a sharper increase of SCLC risk for pack-years ranged 0 to approximately 50. The former smokers with longer cessation showed a 43%(quit_for_5-9 years) to 89%(quit_for_>= 20 years) declined SCLC risk vs. subjects who had quit smoking <5 years. Compared with non-COPD subjects, smoking behaviors showed a significantly higher effect on SCLC risk among COPD subjects, and further, COPD patients showed a 1.86-fold higher risk of SCLC. Furthermore, smoking behaviors on SCLC risk were significantly mediated through COPD which accounted for 0.70% to 7.55% of total effects. Interpretation: This is the largest pooling study that provides improved understanding of smoking on SCLC, and further demonstrates a causal pathway through COPD that warrants further experimental study. (C) 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). C1 [Huang, Ruyi; Wei, Yongyue; Su, Li; Zhang, Ruyang; Christiani, David C.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Huang, Ruyi] E Da Hosp, Dept Med Educ, Kaohsiung, Taiwan. [Huang, Ruyi] I Shou Univ, Kaohsiung, Taiwan. [Hung, Rayjean J.; Zong, Xuchen] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Liu, Geoffrey] Univ Toronto, Princess Margaret Canc Ctr, Univ Hlth Network, Toronto, ON, Canada. [Zhang, Zuo-Feng] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Jonsson Comprehens Canc Ctr, Dept Epidemiol, Los Angeles, CA USA. [Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA. [Brueske, Irene; Heinrich, Joachim] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 1, Neuherberg, Germany. [Hong, Yun-Chul] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 151, South Korea. [Kim, Jin Hee] Seoul Natl Univ, Grad Sch Publ Hlth, Dept Environm Hlth, Seoul, South Korea. [Cote, Michele; Wenzlaff, Angela; Schwartz, Ann G.] Wayne State Univ, Barbara Ann Karmanos Canc Inst, Detroit, MI USA. [Cote, Michele; Wenzlaff, Angela; Schwartz, Ann G.] Wayne State Univ, Dept Oncol, Detroit, MI USA. [Stucker, Isabelle] French Inst Hlth & Med Res, Ctr Res Epidemiol & Populat Hlth, Villejuif, France. [Mclaughlin, L. John] Publ Hlth Ontario, Toronto, ON, Canada. [Marcus, Michael W.; Davies, Michael P. A.; Liloglou, Triantafillos; Field, John K.] Univ Liverpool, Inst Translat Med, Dept Mol & Clin Canc Med, Liverpool L69 3BX, Merseyside, England. [Matsuo, Keitaro] Aichi Canc Ctr, Res Inst, Div Mol Med, Nagoya, Aichi 464, Japan. [Barnett, Matt; Thornquist, Mark; Goodman, Gary] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Wang, Yi; Chen, Size; Yang, Ping] Mayo Clin, Dept Hlth Sci Res, Div Epidemiol, Rochester, MN USA. [Wang, Yi] Wenzhou Med Univ, Sch Environm Sci & Publ Hlth, Wenzhou, Peoples R China. [Chen, Size] Guangdong Pharmaceut Univ, Affiliated Hosp 1, Dept Oncol, Guangzhou, Guangdong, Peoples R China. [Duell, Eric J.] Catalan Inst Oncol ICO IDIBELL, Unit Nutr & Canc, Barcelona, Spain. [Andrew, Angeline S.] Dartmouth Coll, Norris Cotton Canc Ctr, Geisel Sch Med, Lebanon, NH 03756 USA. [Lazarus, Philip; Muscat, Joshua] Penn State Coll Med, Hershey, PA USA. [Woll, Penella; Horsman, Janet; Teare, M. Dawn] Univ Sheffield, Sheffield Sch Hlth & Related Res, Expt Canc Med Ctr, Sheffield, S Yorkshire, England. [Flugelman, Anath; Rennert, Gad] Carmel Hosp, Clalit Natl Israeli Canc Control Ctr, Haifa, Israel. [Flugelman, Anath; Rennert, Gad] Technion Israel Inst Technol, IL-32000 Haifa, Israel. [Zhang, Yan; Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany. [Brenner, Hermann] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany. [Stegmaier, Christa] Saarland Canc Registry, Saarbrucken, Germany. [van der Heijden, Erik H. F. M.; Aben, Katja; Kiemeney, Lambertus] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, NL-6525 ED Nijmegen, Netherlands. [Aben, Katja] Netherlands Comprehens Canc Org, Utrecht, Netherlands. [Barros-Dios, Juan; Perez-Rios, Monica; Ruano-Ravina, Alberto] Univ Hosp Complex Santiago Compostela, Serv Prevent Med, Santiago De Compostela, Spain. [Caporaso, Neil E.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [Bertazzi, Pier Alberto; Landi, Maria Teresa] Osped Maggiore Policlin, Fdn IRCCS Ca Granda, Epidemiol Unit, Milan, Italy. [Bertazzi, Pier Alberto; Landi, Maria Teresa] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy. [Wei, Yongyue; Zhang, Ruyang; Dai, Juncheng; Shen, Hongbing] Nanjing Med Univ, Collaborat Innovat Ctr Canc Personalized Med, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Dept Epidemiol & Biostat,Sch Publ Hlth, Nanjing, Jiangsu, Peoples R China. [Fernandez-Tardon, Guillermo; Tardon, Adonina; Christiani, David C.] Univ Oviedo, Dept Prevent Med & Publ Hlth, Spanish Consortium Res Epidemiol & Publ Hlth CIBE, Oviedo, Spain. [Rodriguez-Suarez, Marta] CSIC, Dept Conservat Biol, Estn Biol Donana, E-41080 Seville, Spain. [Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Div,Dept Med, Boston, MA USA. [Wei, Yongyue; Zhang, Ruyang] Nanjing Med Univ, Sch Publ Hlth, Joint Lab Hlth & Environm Risk Assessment HERA, Nanjing, Jiangsu, Peoples R China. RP Christiani, DC (reprint author), 665 Huntington Ave,Bldg 1 Room, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu RI van der Heijden, H.F.M. (Erik)/D-3774-2009; Hung, Rayjean/A-7439-2013; Aben, Katja/G-9686-2016; CSIC, EBD Donana/C-4157-2011; bertazzi, pietro alberto/D-5039-2017; OI van der Heijden, H.F.M. (Erik)/0000-0003-3596-518X; Aben, Katja/0000-0002-0214-2147; CSIC, EBD Donana/0000-0003-4318-6602; bertazzi, pietro alberto/0000-0003-3475-2449; Huang, Ruyi/0000-0001-6867-7171 FU Intramural NIH HHS; NCI NIH HHS [CA060691, CA074386, CA090578, CA09142, CA092824, CA167462, CA68384, CA77954, CA80127, CA84354, CA90833, CA96134, P30 CA022453, P30 CA023108, P30CA022453, R35 CA197449, U01 CA063673, UM1 CA167462]; NIDA NIH HHS [DA11386]; NIEHS NIH HHS [ES00002, ES011667]; PHS HHS [HHSN261201000028C] NR 71 TC 6 Z9 6 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2352-3964 J9 EBIOMEDICINE JI EBioMedicine PD NOV PY 2015 VL 2 IS 11 BP 1677 EP 1685 DI 10.1016/j.ebiom.2015.09.031 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA CX8OA UT WOS:000365962100033 PM 26870794 ER PT J AU Kim, HL Halabi, S Li, P Mayhew, G Simko, J Nixon, AB Small, EJ Rini, B Morris, MJ Taplin, ME George, D AF Kim, Hyung L. Halabi, Susan Li, Ping Mayhew, Greg Simko, Jeff Nixon, Andrew B. Small, Eric J. Rini, Brian Morris, Michael J. Taplin, Mary-Ellen George, Daniel CA Alliance Clinical Trials Oncology TI A Molecular Model for Predicting Overall Survival in Patients with Metastatic Clear Cell Renal Carcinoma: Results from CALGB 90206 (Alliance) SO EBIOMEDICINE LA English DT Article DE Renal cell carcinoma; Prognostic markers; Prognostic signature; Expression profile ID GENE-EXPRESSION; INTERFERON-ALPHA; KIDNEY CANCER; MARKERS; TUMOR; PATHWAY; PCR AB Background:Prognosis associated with metastatic renal cell carcinoma (mRCC) can vary widely. Methods:This study used pretreatment nephrectomy specimens from a randomized phase III trial. Expression levels of candidate genes were determined from archival tumors using the OpenArray (R) platform for TaqMan (R) RT-qPCR. The dataset was randomly divided at 2:1 ratio into training (n = 221) and testing (n = 103) sets to develop a multigene prognostic signature. Findings:Gene expressions were measured in 324 patients. In the training set, multiple models testing 424 candidate genes identified a prognostic signature containing 8 genes plus MSKCC clinical risk factors. In the testing set, the time dependent (td) AUC for a prognostic model containing the 8 genes with and without MSKCC risk factors were 0.72 and 0.69, respectively. The tdAUC for the clinical risk factors alone was 0.61. Additional primary mRCCs from patients with mRCC (n = 12) were sampled in multiple sites and standard deviations of gene expressions within a tumor were used as a measure of heterogeneity. All 8 genes in the final prognostic model met our criteria for minimal heterogeneity. Conclusions:A molecular prognostic signature based on 8 genes was developed and is ready for external validation in this patient population and other related settings such as nonmetastatic RCC. (C) 2015 The Authors. Published by Elsevier B.V. C1 [Kim, Hyung L.; Li, Ping] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Halabi, Susan; George, Daniel] Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA. [Halabi, Susan; George, Daniel] Duke Univ, Alliance Stat & Data Ctr, Durham, NC USA. [Mayhew, Greg; Nixon, Andrew B.] GeneCentr Diagnost, Durham, NC USA. [Simko, Jeff; Small, Eric J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Rini, Brian] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Morris, Michael J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Taplin, Mary-Ellen] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kim, HL (reprint author), Cedars Sinai Med Ctr, 8700 Beverly Blvd, Los Angeles, CA 90048 USA. EM kimhl@cshs.org OI Morris, Michael J./0000-0002-9454-0096 FU NCI NIH HHS [R01 CA133072] NR 34 TC 5 Z9 5 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2352-3964 J9 EBIOMEDICINE JI EBioMedicine PD NOV PY 2015 VL 2 IS 11 BP 1814 EP 1820 DI 10.1016/j.ebiom.2015.09.012 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA CX8OA UT WOS:000365962100046 PM 26870806 ER PT J AU Moura, LMVR Mendez, DY De Jesus, J Andrade, RA Weissman, JS Vickrey, BG Hoch, DB AF Moura, Lidia M. V. R. Mendez, Diego Yacaman De Jesus, Jonathan Andrade, Rogger A. Weissman, Joel S. Vickrey, Barbara G. Hoch, Daniel B. TI Association of adherence to epilepsy quality standards with seizure control SO EPILEPSY RESEARCH LA English DT Article DE Epilepsy care; Epilepsy quality measures; Seizure control ID AMERICAN ACADEMY; ILAE COMMISSION; OF-CARE; DEFINITION; NEUROLOGY; PATIENT; ADULTS; SUBCOMMITTEE; IMPROVEMENT; FREQUENCY AB Objective: We assessed the relationship between adherence to epilepsy quality measures (EQM) and seizure control over 2-3 years in a retrospective cohort study. Methods: 6150 patients were identified at two large academic medical centers with a primary or secondary diagnosis of epilepsy, were 18-85 years old and seen in outpatient general neurology or epilepsy units between June 2011 and May 2014. Patients were included if: their initial visit was between June 2011 and June 2012, treatment was with >= 1 anti-seizure drug, there was >= 1 visit per year during the timeframe, and seizure frequency was documented at initial and final visits, yielding 162 patients/1055 visits from which socio-demographic, clinical and care quality data were abstracted. Quality care was assessed as (1) percent adherence to up to 8 eligible EQM, and (2) defect-free care (DFC: adherence to all eligible EQM). Seizure control (SC) was defined as >= 50% reduction in average seizures/month between initial and final visits. Chi-square and t-test compared care quality with seizure control. Logistic regression was used to assess the relationships between SC, quality of care and subspecialist involvement. Results: Care quality, reflected by documentation of seizure frequency, addressing therapeutic interventions, and referral to a comprehensive epilepsy center, all exceeded 80% adherence. Care quality as reflected by documentation of seizure type, etiology or syndrome; assessment of side effects, counseling about epilepsy safety and women's issues, and screening for psychiatric disorders ranged from 40 to 57%. Mean EQM adherence across all applicable measures was associated with greater seizure control (p=0.0098). DFC was low (=8%) and did not covarsr with seizure control (p = 0.55). The SC and non-SC groups only differed on epilepsy etiology (p = 0.04). Exploratory analysis showed that mean quality scores are associated with seizure control (OR = 4.9 [1.3-18.5], p = 0.017) while controlling for the effect of subspecialty involvement as a possible confounding variable. Conclusions: Average quality of care but not defect-free care was associated with seizure control in this retrospective cohort. (C) 2015 Elsevier B.V. All rights reserved. C1 [Moura, Lidia M. V. R.; Mendez, Diego Yacaman; De Jesus, Jonathan; Andrade, Rogger A.; Hoch, Daniel B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Weissman, Joel S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02120 USA. [Weissman, Joel S.] Harvard Univ, Dept Hlth Policy & Management, T Chan Sch Publ Hlth, Boston, MA 02115 USA. [Vickrey, Barbara G.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. [Vickrey, Barbara G.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Moura, LMVR (reprint author), Massachusetts Gen Hosp, Wang Neurol 720, 55 Fruit St, Boston, MA 02114 USA. EM lidia.moura@mgh.harvard.edu; dymendez@partners.org; jdejesus5@partners.org; raandrade@partners.org; jweissman@partners.org; bvickrey@ucla.edu; dhoch@partners.org FU Eisai, Inc through a Epilepsy Foundation Research Training Fellowship for Clinicians FX This study is supported by Eisai, Inc through a 2014 Epilepsy Foundation Research Training Fellowship for Clinicians. NR 41 TC 3 Z9 3 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 EI 1872-6844 J9 EPILEPSY RES JI Epilepsy Res. PD NOV PY 2015 VL 117 BP 35 EP 41 DI 10.1016/j.eplepsyres.2015.08.008 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA CY2ID UT WOS:000366231100007 PM 26370916 ER PT J AU Gersner, R Ekstein, D Dhamne, SC Schachter, SC Rotenberg, A AF Gersner, R. Ekstein, D. Dhamne, S. C. Schachter, S. C. Rotenberg, A. TI Huperzine A prophylaxis against pentylenetetrazole-induced seizures in rats is associated with increased cortical inhibition SO EPILEPSY RESEARCH LA English DT Article DE Huperzine A; PTZ; Rat; Cortical inhibition; Paired-pulse TMS ID TRANSCRANIAL MAGNETIC STIMULATION; GENERALIZED EPILEPSY; ALZHEIMERS-DISEASE; ANESTHETIZED RATS; EXCITABILITY; RECEPTORS; TRANSMISSION; MECHANISM; BRAIN; MODEL AB Huperzine A (HupA) is a naturally occurring compound found in the firmoss Huperzia serrata. While HupA is a potent acetylcholinesterase inhibitor, its full pharmacologic profile is incompletely described. Since previous works suggested a capacity for HupA to prophylax against seizures, we tested the HupA antiepileptic potential in pentylenetetrazole (PTZ) rat epilepsy model and explored its mechanism of action by spectral EEG analysis and by paired-pulse transcranial magnetic stimulation (ppTMS), a measure of GABA-mediated intracortical inhibition. We tested whether HupA suppresses seizures in the rat PTZ acute seizure model, and quantified latency to first myoclonus and to generalized tonic-clonic seizure, and spike frequency on EEG. Additionally, we measured power in the EEG gamma frequency band which is associated with GABAergic cortical interneuron activation. Then, as a step toward further examining the HupA antiepileptic mechanism of action, we tested long-interval intracortical inhibition (LICI) using ppTMS coupled with electromyography to assess whether HupA augments GABA-mediated paired-pulse inhibition of the motor evoked potential. We also tested whether the HupA effect on paired-pulse inhibition was central or peripheral by comparison of outcomes following administration of HupA or the peripheral acetylcholinesterase inhibitor pyridostigmine. We also tested whether the HupA effect was dependent on central muscarinic or GABA(A) receptors by co-administration of HupA and atropine or PTZ, respectively. In tests of antiepileptic potential, HupA suppressed seizures and epileptic spikes on EEG. Spectral EEG analysis also revealed enhanced gamma frequency band power with HupA treatment. By ppTMS we found that HupA increases intracortical inhibition and blocks PTZ-induced cortical excitation. Atropine co-administration with HupA did not alter HupA-induced intracortical inhibition suggesting independent of muscarinic acetylcholine receptors mechanism in this model. Last, pyridostigmine did not affect the ppTMS-measured cortical inhibition suggesting that HupA-induced effect is centrally-mediated. Our data support antiepileptic HupA applications, and suggest that such activity may be via enhancement of GABAergic intracortical inhibition. (C) 2015 Elsevier B.V. All rights reserved. C1 [Gersner, R.; Dhamne, S. C.; Rotenberg, A.] Harvard Univ, Sch Med, Dept Neurol, FM Kirby Neurobiol Ctr,Boston Childrens Hosp, Boston, MA 02115 USA. [Gersner, R.; Dhamne, S. C.; Rotenberg, A.] Harvard Univ, Sch Med, Dept Neurol, Neuromodulat Program,Boston Childrens Hosp, Boston, MA 02115 USA. [Ekstein, D.] Hadassah Hebrew Univ, Med Ctr, Agnes Ginges Ctr Human Neurogenet, Dept Neurol, Jerusalem, Israel. [Schachter, S. C.] Harvard Univ, Sch Med, Dept Neurol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Schachter, S. C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Rotenberg, A (reprint author), Boston Childrens Hosp, Dept Neurol, 300 Longwood Ave,Fegan 9, Boston, MA 02115 USA. EM alexander.rotenberg@childrens.harvard.edu FU Center for Integration of Medicine and Innovative Technology (CIMIT), Translational Research Program (TRP), Boston Children's Hospital; Neuromodulation Program, Boston Children's Hospital FX This study was supported financially by the Center for Integration of Medicine and Innovative Technology (CIMIT), Translational Research Program (TRP), Boston Children's Hospital and the Neuromodulation Program, Boston Children's Hospital. NR 35 TC 5 Z9 5 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 EI 1872-6844 J9 EPILEPSY RES JI Epilepsy Res. PD NOV PY 2015 VL 117 BP 97 EP 103 DI 10.1016/j.eplepsyres.2015.08.012 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA CY2ID UT WOS:000366231100017 PM 26432930 ER PT J AU Januszkiewicz, L Vegh, E Borgquist, R Bose, A Sharma, A Orencole, M Mela, T Singh, JP Parks, KA AF Januszkiewicz, Lukasz Vegh, Eszter Borgquist, Rasmus Bose, Abhishek Sharma, Ajay Orencole, Mary Mela, Theofanie Singh, Jagmeet P. Parks, Kimberly A. TI Prognostic implication of baseline PR interval in cardiac resynchronization therapy recipients SO HEART RHYTHM LA English DT Article DE Cardiac resynchronization therapy; PR interval; First-degree atrioventricular block; Biventricular pacemaker; Heart failure ID CHRONIC HEART-FAILURE; 1ST-DEGREE ATRIOVENTRICULAR-BLOCK; ATRIAL-FIBRILLATION; OUTCOMES; TRIAL; REGURGITATION; PREDICTORS; FLOW; CARE; ECG AB BACKGROUND Prolongation of the baseline ECG PR interval is frequently encountered among cardiac resynchronization therapy (CRT) recipients. There are conflicting data regarding the association of a prolonged PR interval with long-term clinical outcome in this patient group. OBJECTIVE The purpose of this study was to compare clinical outcomes and response to CRT in patients with normal (<200 ms) vs prolonged (>= 200 ms) baseline PR interval. METHODS In this study, 283 patients (normal PR interval: n = 158; prolonged PR interval: n = 125) with documented baseline intrinsic PR interval were followed for 3 years after CRT implantation. The study population consisted of 24.7% women (mean age 66 +/- 13 years, left ventricular ejection fraction 24% +/- 7%). RESULTS A Cox proportional hazard model identified baseline PR interval as a predictor of the composite end-point (all-cause mortality, heart failure hospitalization, left ventricular assist device implantation, and heart transplantation) in univariate analysis (hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.02-2.17, P = .04) but not in multivariate analysis. It also predicted heart failure hospitalization in univariate (HR 1.6, 95% CI 1.1-2.4, P = .02) and multivariate analysis (HR 1.6, 95% CI 1.0-2.3, P = .03). A prolonged PR interval was associated with lower probability of reverse remodeling defined as > 10% improvement in ejection fraction (64% vs 77%, P = .057), especially in patients with non-left bundle branch block ECG morphology (41% vs 68%, P = .03). CONCLUSION Among patients with CRT, a prolonged baseline PR interval is an independent predictor of worse prognosis and Lower probability of reverse remodeling, especially for patients with nonleft bundle branch block morphology on ECG. C1 [Januszkiewicz, Lukasz; Vegh, Eszter; Borgquist, Rasmus; Bose, Abhishek; Sharma, Ajay; Orencole, Mary; Mela, Theofanie; Singh, Jagmeet P.; Parks, Kimberly A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02459 USA. [Januszkiewicz, Lukasz] Med Univ Warsaw, Dept Cardiol 1, Warsaw, Poland. RP Parks, KA (reprint author), Harvard Univ, Resynchronizat & Adv Cardiac Therapeut Program, Massachusetts Gen Hosp, Sch Med, Boston, MA 02459 USA. EM KAParks@Partners.org FU Worldwide Institute Supporting Exchange scholarship; governmental funding of clinical research within the Swedish National Health Service; Maggie Stephens Foundation; Swedish Medical Society; Biotronik; Boston Scientific; Medtronic; Sorin Group; St. Jude Medical FX Drs. Januszkiewicz and Vegh contributed equally to this work as first co-authors. Ibis work was supported in part by the Worldwide Institute Supporting Exchange scholarship. Dr. Borgquist was supported by governmental funding of clinical research within the Swedish National Health Service, the Maggie Stephens Foundation, and the Swedish Medical Society. Dr. Singh receives research grants, and lecture and consulting fees from Biotronik, Boston Scientific, Medtronic, Sorin Group, and St. Jude Medical. Dr. Parks has received lecture honoraria and consulting fees from Biotronik, Medtronic, and St. Jude Medical. NR 30 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 EI 1556-3871 J9 HEART RHYTHM JI Heart Rhythm PD NOV PY 2015 VL 12 IS 11 BP 2256 EP 2262 DI 10.1016/j.hrthm.2015.06.016 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA CY0RG UT WOS:000366112600011 PM 26066291 ER PT J AU Halaney, DL Zahedivash, A Phipps, JE Wang, TY Dwelle, J Le Saux, CJ Asmis, R Milner, TE Feldman, MD AF Halaney, David L. Zahedivash, Aydin Phipps, Jennifer E. Wang, Tianyi Dwelle, Jordan Le Saux, Claude Jourdan Asmis, Reto Milner, Thomas E. Feldman, Marc D. TI Differences in forward angular light scattering distributions between M1 and M2 macrophages SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE macrophage; M1 M2; angular light scattering ID LOW-COHERENCE INTERFEROMETRY; MITOCHONDRIAL MEMBRANE FRAGMENTS; TUMOR-ASSOCIATED MACROPHAGES; IN-SITU; MONONUCLEAR PHAGOCYTES; BIOLOGICAL CELLS; RAT-LIVER; ATHEROSCLEROSIS; POLARIZATION; DIFFERENTIATION AB The ability to distinguish macrophage subtypes noninvasively could have diagnostic potential in cancer, atherosclerosis, and diabetes, where polarized M1 and M2 macrophages play critical and often opposing roles. Current methods to distinguish macrophage subtypes rely on tissue biopsy. Optical imaging techniques based on light scattering are of interest as they can be translated into biopsy-free strategies. Because mitochondria are relatively strong subcellular light scattering centers, and M2 macrophages are known to have enhanced mitochondrial biogenesis compared to M1, we hypothesized that M1 and M2 macrophages may have different angular light scattering profiles. To test this, we developed an in vitro angle-resolved forward light scattering measurement system. We found that M1 and M2 macrophage monolayers scatter relatively unequal amounts of light in the forward direction between 1.6 deg and 3.2 deg with M2 forward scattering significantly more light than M1 at increasing angles. The ratio of forward scattering can be used to identify the polarization state of macrophage populations in culture. (C) 2015 Society of Photo-Optical Instrumentation Engineers (SPIE) C1 [Halaney, David L.; Phipps, Jennifer E.; Le Saux, Claude Jourdan; Feldman, Marc D.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Cardiol, San Antonio, TX 78229 USA. [Halaney, David L.; Dwelle, Jordan; Feldman, Marc D.] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX 78229 USA. [Zahedivash, Aydin; Wang, Tianyi; Dwelle, Jordan; Milner, Thomas E.] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA. [Asmis, Reto] Univ Texas Hlth Sci Ctr San Antonio, Dept Clin Lab Sci, San Antonio, TX 78229 USA. [Asmis, Reto] Univ Texas Hlth Sci Ctr San Antonio, Dept Biochem, San Antonio, TX 78229 USA. RP Feldman, MD (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Cardiol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM feldmanm@uthscsa.edu OI Halaney, David/0000-0003-4437-0516 FU Veterans Health Administration Merit Grant [I01 BX000397]; Janey and Dolph Briscoe Center for Cardiovascular Research (San Antonio, Texas); Clayton Foundation for Biomedical Research (Houston, Texas); National Institutes of Health [T32 HL007446]; American Society for Laser, Medicine, and Surgery Research Grant; American Heart Association Post-doctoral Award [13POST17080074] FX This work was supported by the Veterans Health Administration Merit Grant I01 BX000397; the Janey and Dolph Briscoe Center for Cardiovascular Research (San Antonio, Texas); the Clayton Foundation for Biomedical Research (Houston, Texas); the National Institutes of Health (T32 HL007446); an American Society for Laser, Medicine, and Surgery 2013-2014 Research Grant; and an American Heart Association Post-doctoral Award (13POST17080074). NR 59 TC 1 Z9 1 U1 1 U2 4 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD NOV PY 2015 VL 20 IS 11 AR 115002 DI 10.1117/1.JBO.20.11.115002 PG 9 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA CX9IA UT WOS:000366017500026 PM 26538329 ER PT J AU Khaleghi, M Guignard, J Furlong, C Rosowski, JJ AF Khaleghi, Morteza Guignard, Jeremie Furlong, Cosme Rosowski, John J. TI Simultaneous full-field 3-D vibrometry of the human eardrum using spatial-bandwidth multiplexed holography SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE three-dimensional displacement measurements; digital holography; image registration; multiplexed holography; tympanic membrane ID TYMPANIC MEMBRANE; DIGITAL HOLOGRAPHY; SAMPLING THEOREM; ZERO-ORDER; MOTION; EAR; REGISTRATION; TRANSFORM; EXTENSION; VIBRATION AB Holographic interferometric methods typically require the use of three sensitivity vectors in order to obtain three-dimensional (3-D) information. Methods based on multiple directions of illumination have limited applications when studying biological tissues that have temporally varying responses such as the tympanic membrane (TM). Therefore, to measure 3-D displacements in such applications, the measurements along all the sensitivity vectors have to be done simultaneously. We propose a multiple-illumination directions approach to measure 3-D displacements from a single-shot hologram that contains displacement information from three sensitivity vectors. The hologram of an object of interest is simultaneously recorded with three incoherently superimposed pairs of reference and object beams. The incident off-axis angles of the reference beams are adjusted such that the frequency components of the multiplexed hologram are completely separate. Because of the differences in the directions and wavelengths of the reference beams, the positions of each reconstructed image corresponding to each sensitivity vector are different. We implemented a registration algorithm to accurately translate individual components of the hologram into a single global coordinate system to calculate 3-D displacements. The results include magnitudes and phases of 3-D sound-induced motions of a human cadaveric TM at several excitation frequencies showing modal and traveling wave motions on its surface. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI. C1 [Khaleghi, Morteza; Furlong, Cosme] Worcester Polytech Inst, Dept Mech Engn, Ctr Holog Studies & Laser MicromechaTron CHSLT, Worcester, MA 01609 USA. [Guignard, Jeremie; Furlong, Cosme; Rosowski, John J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Guignard, Jeremie; Furlong, Cosme; Rosowski, John J.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Khaleghi, M (reprint author), Worcester Polytech Inst, Dept Mech Engn, Ctr Holog Studies & Laser MicromechaTron CHSLT, Worcester, MA 01609 USA. EM mkm@wpi.edu FU National Institute on Deafness and other Communication Disorders (NIDCD); Massachusetts Eye and Ear Infirmary (MEEI); Swiss National Science Foundation (SNSF); Mechanical Engineering Department at Worcester Polytechnic Institute FX This work was supported by the National Institute on Deafness and other Communication Disorders (NIDCD), Massachusetts Eye and Ear Infirmary (MEEI), the Swiss National Science Foundation (SNSF), and the Mechanical Engineering Department at Worcester Polytechnic Institute. We also acknowledge the support of all the members of the CHSLT labs at WPI and Eaton-Peabody labs at MEEI, in particular Ellery Harrington and Jeffrey Tao Cheng. NR 35 TC 4 Z9 4 U1 0 U2 10 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD NOV PY 2015 VL 20 IS 11 AR 111202 DI 10.1117/1.JBO.20.11.111202 PG 11 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA CX9IA UT WOS:000366017500008 PM 25984986 ER PT J AU Nagle, KF Eadie, TL Yorkston, KM AF Nagle, Kathleen F. Eadie, Tanya L. Yorkston, Kathryn M. TI Everyday listeners' impressions of speech produced by individuals with adductor spasmodic dysphonia SO JOURNAL OF COMMUNICATION DISORDERS LA English DT Article DE Adductor spasmodic dysphonia; Overall severity; Everyday listeners; Perceptual rating ID QUALITY-OF-LIFE; VOICE DISORDERS; PERCEPTIONS; SPEAKERS; CHILDREN; PERSONALITY; RATINGS; DISEASE AB Individuals with adductor spasmodic dysphonia (ADSD) have reported that unfamiliar communication partners appear to judge them as sneaky, nervous or not intelligent, apparently based on the quality of their speech; however, there is minimal research into the actual everyday perspective of listening to ADSD speech. The purpose of this study was to investigate the impressions of listeners hearing ADSD speech for the first time using a mixed-methods design. Everyday listeners were interviewed following sessions in which they made ratings of ADSD speech. A semi-structured interview approach was used and data were analyzed using thematic content analysis. Three major themes emerged: (1) everyday listeners make judgments about speakers with ADSD; (2) ADSD speech does not sound normal to everyday listeners; and (3) rating overall severity is difficult for everyday listeners. Participants described ADSD speech similarly to existing literature; however, some listeners inaccurately extrapolated speaker attributes based solely on speech samples. Listeners may draw erroneous conclusions about individuals with ADSD and these biases may affect the communicative success of these individuals. Results have implications for counseling individuals with ADSD, as well as the need for education and awareness about ADSD. (C) 2015 Elsevier Inc. All rights reserved. C1 [Nagle, Kathleen F.; Eadie, Tanya L.; Yorkston, Kathryn M.] Seton Hall Univ, Sch Hlth & Med Sci, Dept Speech Language Pathol, S Orange, NJ 07079 USA. RP Nagle, KF (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. FU University of Washington Department of Speech & Hearing Sciences FX This study was funded in part by the University of Washington Department of Speech & Hearing Sciences. We are grateful to Katie Smith for transcribing the interviews and to the speakers and listeners for their time and effort. NR 47 TC 1 Z9 1 U1 4 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0021-9924 EI 1873-7994 J9 J COMMUN DISORD JI J. Commun. Disord. PD NOV-DEC PY 2015 VL 58 BP 1 EP 13 DI 10.1016/j.jcomdis.2015.07.001 PG 13 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA CX8DT UT WOS:000365933500001 PM 26209746 ER PT J AU Luke, B Stern, JE Kotelchuck, M Declercq, ER Cohen, B Diop, H AF Luke, Barbara Stern, Judy E. Kotelchuck, Milton Declercq, Eugene R. Cohen, Bruce Diop, Hafsatou TI Birth Outcomes by Infertility Diagnosis Analyses of the Massachusetts Outcomes Study of Assisted Reproductive Technologies (MOSART) SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE assisted reproductive technologies; cesarean section; diagnosis; infertility; outcome and process assessment (health care); pregnancy complications; pregnancy outcomes; reproductive technology assisted ID SART CORS DATABASE; UNITED-STATES; PERINATAL OUTCOMES; PREGNANCY OUTCOMES; WEIGHT; WOMEN; SURVEILLANCE; FERTILIZATION; SUBFERTILITY; COLLECTION AB OBJECTIVE: To evaluate assisted reproductive technology (ART) pregnancy outcomes by infertility diagnosis. STUDY DESIGN: ART data on women who were treated and gave birth in Massachusetts were linked to vital records and hospital utilization data. Live births were categorized by 8 mutually exclusive ART diagnoses. Risks of prematurity, low birthweight (LBW), small-for-gestational age (SGA),large-for-gestational age (LGA), pregnancy hypertension, gestational diabetes, prenatal hospitalizations, and primary cesarean delivery were modeled using logistic regression, adjusted for parental characteristics; treatment parameters, and plurality (adjusted odds ratios [AORs] and 95% confidence intervals); the reference group were pregnancies with the diagnosis of malefactor. RESULTS: Among the 7,354 singleton and twin pregnancies, there were nonsignificant differences in the risks for LBW, SGA, or LGA. Significantly increased risks included gestational diabetes (ovulation disorders, AOR 1.80, 1.35-2.41), prematurity (ovulation disorders, AOR 1.36, 1.08-1.71; other factors, AOR 1.33, 1.05-1.67), prenatal hospital admissions (endometriosis, tubal and other factors, ovulation disorders, and uterine factors, AORs ranging from 1.662.68), and primary cesarean section (uterine factors, AOR 1.96, 1.15-3.36). CONCLUSION: Although the infant outcomes of LBW, SGA, and LGA were generally similar across diagnosis groups, specific diagnoses had greater risks for prematurity, gestational diabetes, prenatal hospital utilization, and primary cesarean delivery. C1 Michigan State Univ, Dept Obstet Gynecol & Reprod Biol, E Lansing, MI 48824 USA. Geisel Sch Med Dartmouth, Dept Obstet & Gynecol, Lebanon, NH USA. Harvard Univ, Sch Med, MassGen Hosp Children, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Community Hlth Sci, Boston, MA USA. Massachusetts Dept Publ Hlth, Boston, MA USA. RP Luke, B (reprint author), Michigan State Univ, Dept Obstet & Gynecol & Reprod Biol, 965 Fee Rd,East Fee Hall,Room 628, E Lansing, MI 48824 USA. EM lukeb@msu.edu FU National Institute of Child Health and Human Development [R01HD064595, R01HD067270] FX Supported by Award Numbers R01HD064595 and R01HD067270 from the National Institute of Child Health and Human Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Child Health and Human Development or the National Institutes of Health. NR 41 TC 3 Z9 3 U1 0 U2 4 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 EI 1943-3565 J9 J REPROD MED JI J. Reprod. Med. PD NOV-DEC PY 2015 VL 60 IS 11-12 BP 480 EP 490 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA CY2MU UT WOS:000366243600004 PM 26775455 ER EF