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2. Lawson Criterion for Ignition Exceeded in an Inertial Fusion Experiment
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Abu-Shawareb, H, Acree, R, Adams, P, Adams, J, Addis, B, Aden, R, Adrian, P, Afeyan, BB, Aggleton, M, Aghaian, L, Aguirre, A, Aikens, D, Akre, J, Albert, F, Albrecht, M, Albright, BJ, Albritton, J, Alcala, J, Alday, C, Alessi, DA, Alexander, N, Alfonso, J, Alfonso, N, Alger, E, Ali, SJ, Ali, ZA, Alley, WE, Amala, P, Amendt, PA, Amick, P, Ammula, S, Amorin, C, Ampleford, DJ, Anderson, RW, Anklam, T, Antipa, N, Appelbe, B, Aracne-Ruddle, C, Araya, E, Arend, M, Arnold, P, Arnold, T, Asay, J, Atherton, LJ, Atkinson, D, Atkinson, R, Auerbach, JM, Austin, B, Auyang, L, Awwal, AS, Ayers, J, Ayers, S, Ayers, T, Azevedo, S, Bachmann, B, Back, CA, Bae, J, Bailey, DS, Bailey, J, Baisden, T, Baker, KL, Baldis, H, Barber, D, Barberis, M, Barker, D, Barnes, A, Barnes, CW, Barrios, MA, Barty, C, Bass, I, Batha, SH, Baxamusa, SH, Bazan, G, Beagle, JK, Beale, R, Beck, BR, Beck, JB, Bedzyk, M, Beeler, RG, Behrendt, W, Belk, L, Bell, P, Belyaev, M, Benage, JF, Bennett, G, Benedetti, LR, Benedict, LX, Berger, R, Bernat, T, Bernstein, LA, Berry, B, Bertolini, L, Besenbruch, G, Betcher, J, Bettenhausen, R, Betti, R, Bezzerides, B, Bhandarkar, SD, Bickel, R, Biener, J, Biesiada, T, Bigelow, K, Bigelow-Granillo, J, Bigman, V, Bionta, RM, Birge, NW, Bitter, M, Black, AC, Bleile, R, Bleuel, DL, Bliss, E, Blue, B, Boehly, T, Boehm, K, Boley, CD, Bonanno, R, Bond, EJ, Bond, T, Bonino, MJ, Borden, M, Bourgade, J-L, Bousquet, J, Bowers, J, Bowers, M, Boyd, R, Bozek, A, Bradley, DK, Bradley, KS, Bradley, PA, Bradley, L, Brannon, L, Brantley, PS, Braun, D, Braun, T, Brienza-Larsen, K, Briggs, TM, Britten, J, Brooks, ED, Browning, D, Bruhn, MW, Brunner, TA, Bruns, H, Brunton, G, Bryant, B, Buczek, T, Bude, J, Buitano, L, Burkhart, S, Burmark, J, Burnham, A, Burr, R, Busby, LE, Butlin, B, Cabeltis, R, Cable, M, Cabot, WH, Cagadas, B, Caggiano, J, Cahayag, R, Caldwell, SE, Calkins, S, Callahan, DA, Calleja-Aguirre, J, Camara, L, Camp, D, Campbell, EM, Campbell, JH, Carey, B, Carey, R, Carlisle, K, Carlson, L, Carman, L, Carmichael, J, Carpenter, A, Carr, C, Carrera, JA, Casavant, D, Casey, A, Casey, DT, Castillo, A, Castillo, E, Castor, JI, Castro, C, Caughey, W, Cavitt, R, Celeste, J, Celliers, PM, Cerjan, C, Chandler, G, Chang, B, Chang, C, Chang, J, Chang, L, Chapman, R, Chapman, T, Chase, L, Chen, H, Chen, K, Chen, L-Y, Cheng, B, Chittenden, J, Choate, C, Chou, J, Chrien, RE, Chrisp, M, Christensen, K, Christensen, M, Christopherson, AR, Chung, M, Church, JA, Clark, A, Clark, DS, Clark, K, Clark, R, Claus, L, Cline, B, Cline, JA, Cobble, JA, Cochrane, K, Cohen, B, Cohen, S, Collette, MR, Collins, G, Collins, LA, Collins, TJB, Conder, A, Conrad, B, Conyers, M, Cook, AW, Cook, D, Cook, R, Cooley, JC, Cooper, G, Cope, T, Copeland, SR, Coppari, F, Cortez, J, Cox, J, Crandall, DH, Crane, J, Craxton, RS, Cray, M, Crilly, A, Crippen, JW, Cross, D, Cuneo, M, Cuotts, G, Czajka, CE, Czechowicz, D, Daly, T, Danforth, P, Darbee, R, Darlington, B, Datte, P, Dauffy, L, Davalos, G, Davidovits, S, Davis, P, Davis, J, Dawson, S, Day, RD, Day, TH, Dayton, M, Deck, C, Decker, C, Deeney, C, DeFriend, KA, Deis, G, Delamater, ND, Delettrez, JA, Demaret, R, Demos, S, Dempsey, SM, Desjardin, R, Desjardins, T, Desjarlais, MP, Dewald, EL, DeYoreo, J, Diaz, S, Dimonte, G, Dittrich, TR, Divol, L, Dixit, SN, Dixon, J, Dodd, ES, Dolan, D, Donovan, A, Donovan, M, Döppner, T, Dorrer, C, Dorsano, N, Douglas, MR, Dow, D, Downie, J, Downing, E, Dozieres, M, Draggoo, V, Drake, D, Drake, RP, Drake, T, Dreifuerst, G, DuBois, DF, DuBois, PF, Dunham, G, Dylla-Spears, R, Dymoke-Bradshaw, AKL, Dzenitis, B, Ebbers, C, Eckart, M, Eddinger, S, Eder, D, Edgell, D, Edwards, MJ, Efthimion, P, Eggert, JH, Ehrlich, B, Ehrmann, P, Elhadj, S, Ellerbee, C, Elliott, NS, Ellison, CL, Elsner, F, Emerich, M, Engelhorn, K, England, T, English, E, Epperson, P, Epstein, R, Erbert, G, Erickson, MA, Erskine, DJ, Erlandson, A, Espinosa, RJ, Estes, C, Estabrook, KG, Evans, S, Fabyan, A, Fair, J, Fallejo, R, Farmer, N, Farmer, WA, Farrell, M, Fatherley, VE, Fedorov, M, Feigenbaum, E, Feit, M, Ferguson, W, Fernandez, JC, Fernandez-Panella, A, Fess, S, Field, JE, Filip, CV, Fincke, JR, Finn, T, Finnegan, SM, Finucane, RG, Fischer, M, Fisher, A, Fisher, J, Fishler, B, Fittinghoff, D, Fitzsimmons, P, Flegel, M, Flippo, KA, Florio, J, Folta, J, Folta, P, Foreman, LR, Forrest, C, Forsman, A, Fooks, J, Foord, M, Fortner, R, Fournier, K, Fratanduono, DE, Frazier, N, Frazier, T, Frederick, C, Freeman, MS, Frenje, J, Frey, D, Frieders, G, Friedrich, S, Froula, DH, Fry, J, Fuller, T, Gaffney, J, Gales, S, Le Galloudec, B, Le Galloudec, KK, Gambhir, A, Gao, L, Garbett, WJ, Garcia, A, Gates, C, Gaut, E, Gauthier, P, Gavin, Z, Gaylord, J, Geissel, M, Génin, F, Georgeson, J, Geppert-Kleinrath, H, Geppert-Kleinrath, V, Gharibyan, N, Gibson, J, Gibson, C, Giraldez, E, Glebov, V, Glendinning, SG, Glenn, S, Glenzer, SH, Goade, S, Gobby, PL, Goldman, SR, Golick, B, Gomez, M, Goncharov, V, Goodin, D, Grabowski, P, Grafil, E, Graham, P, Grandy, J, Grasz, E, Graziani, F, Greenman, G, Greenough, JA, Greenwood, A, Gregori, G, Green, T, Griego, JR, Grim, GP, Grondalski, J, Gross, S, Guckian, J, Guler, N, Gunney, B, Guss, G, Haan, S, Hackbarth, J, Hackel, L, Hackel, R, Haefner, C, Hagmann, C, Hahn, KD, Hahn, S, Haid, BJ, Haines, BM, Hall, BM, Hall, C, Hall, GN, Hamamoto, M, Hamel, S, Hamilton, CE, Hammel, BA, Hammer, JH, Hampton, G, Hamza, A, Handler, A, Hansen, S, Hanson, D, Haque, R, Harding, D, Harding, E, Hares, JD, Harris, DB, Harte, JA, Hartouni, EP, Hatarik, R, Hatchett, S, Hauer, AA, Havre, M, Hawley, R, Hayes, J, Hayes, S, Hayes-Sterbenz, A, Haynam, CA, Haynes, DA, Headley, D, Heal, A, Heebner, JE, Heerey, S, Heestand, GM, Heeter, R, Hein, N, Heinbockel, C, Hendricks, C, Henesian, M, Heninger, J, Henrikson, J, Henry, EA, Herbold, EB, Hermann, MR, Hermes, G, Hernandez, JE, Hernandez, VJ, Herrmann, MC, Herrmann, HW, Herrera, OD, Hewett, D, Hibbard, R, Hicks, DG, Hill, D, Hill, K, Hilsabeck, T, Hinkel, DE, Ho, DD, Ho, VK, Hoffer, JK, Hoffman, NM, Hohenberger, M, Hohensee, M, Hoke, W, Holdener, D, Holdener, F, Holder, JP, Holko, B, Holunga, D, Holzrichter, JF, Honig, J, Hoover, D, Hopkins, D, Berzak Hopkins, L, Hoppe, M, Hoppe, ML, Horner, J, Hornung, R, Horsfield, CJ, Horvath, J, Hotaling, D, House, R, Howell, L, Hsing, WW, Hu, SX, Huang, H, Huckins, J, Hui, H, Humbird, KD, Hund, J, Hunt, J, Hurricane, OA, Hutton, M, Huynh, KH-K, Inandan, L, Iglesias, C, Igumenshchev, IV, Izumi, N, Jackson, M, Jackson, J, Jacobs, SD, James, G, Jancaitis, K, Jarboe, J, Jarrott, LC, Jasion, D, Jaquez, J, Jeet, J, Jenei, AE, Jensen, J, Jimenez, J, Jimenez, R, Jobe, D, Johal, Z, Johns, HM, Johnson, D, Johnson, MA, Gatu Johnson, M, Johnson, RJ, Johnson, S, Johnson, SA, Johnson, T, Jones, K, Jones, O, Jones, M, Jorge, R, Jorgenson, HJ, Julian, M, Jun, BI, Jungquist, R, Kaae, J, Kabadi, N, Kaczala, D, Kalantar, D, Kangas, K, Karasiev, VV, Karasik, M, Karpenko, V, Kasarky, A, Kasper, K, Kauffman, R, Kaufman, MI, Keane, C, Keaty, L, Kegelmeyer, L, Keiter, PA, Kellett, PA, Kellogg, J, Kelly, JH, Kemic, S, Kemp, AJ, Kemp, GE, Kerbel, GD, Kershaw, D, Kerr, SM, Kessler, TJ, Key, MH, Khan, SF, Khater, H, Kiikka, C, Kilkenny, J, Kim, Y, Kim, Y-J, Kimko, J, Kimmel, M, Kindel, JM, King, J, Kirkwood, RK, Klaus, L, Klem, D, Kline, JL, Klingmann, J, Kluth, G, Knapp, P, Knauer, J, Knipping, J, Knudson, M, Kobs, D, Koch, J, Kohut, T, Kong, C, Koning, JM, Koning, P, Konior, S, Kornblum, H, Kot, LB, Kozioziemski, B, Kozlowski, M, Kozlowski, PM, Krammen, J, Krasheninnikova, NS, Kraus, B, Krauser, W, Kress, JD, Kritcher, AL, Krieger, E, Kroll, JJ, Kruer, WL, Kruse, MKG, Kucheyev, S, Kumbera, M, Kumpan, S, Kunimune, J, Kustowski, B, Kwan, TJT, Kyrala, GA, Laffite, S, Lafon, M, LaFortune, K, Lahmann, B, Lairson, B, Landen, OL, Langenbrunner, J, Lagin, L, Land, T, Lane, M, Laney, D, Langdon, AB, Langer, SH, Langro, A, Lanier, NE, Lanier, TE, Larson, D, Lasinski, BF, Lassle, D, LaTray, D, Lau, G, Lau, N, Laumann, C, Laurence, A, Laurence, TA, Lawson, J, Le, HP, Leach, RR, Leal, L, Leatherland, A, LeChien, K, Lechleiter, B, Lee, A, Lee, M, Lee, T, Leeper, RJ, Lefebvre, E, Leidinger, J-P, LeMire, B, Lemke, RW, Lemos, NC, Le Pape, S, Lerche, R, Lerner, S, Letts, S, Levedahl, K, Lewis, T, Li, CK, Li, H, Li, J, Liao, W, Liao, ZM, Liedahl, D, Liebman, J, Lindford, G, Lindman, EL, Lindl, JD, Loey, H, London, RA, Long, F, Loomis, EN, Lopez, FE, Lopez, H, Losbanos, E, Loucks, S, Lowe-Webb, R, Lundgren, E, Ludwigsen, AP, Luo, R, Lusk, J, Lyons, R, Ma, T, Macallop, Y, MacDonald, MJ, MacGowan, BJ, Mack, JM, Mackinnon, AJ, MacLaren, SA, MacPhee, AG, Magelssen, GR, Magoon, J, Malone, RM, Malsbury, T, Managan, R, Mancini, R, Manes, K, Maney, D, Manha, D, Mannion, OM, Manuel, AM, Mapoles, E, Mara, G, Marcotte, T, Marin, E, Marinak, MM, Mariscal, C, Mariscal, DA, Mariscal, EF, Marley, EV, Marozas, JA, Marquez, R, Marshall, CD, Marshall, FJ, Marshall, M, Marshall, S, Marticorena, J, Martinez, D, Maslennikov, I, Mason, D, Mason, RJ, Masse, L, Massey, W, Masson-Laborde, P-E, Masters, ND, Mathisen, D, Mathison, E, Matone, J, Matthews, MJ, Mattoon, C, Mattsson, TR, Matzen, K, Mauche, CW, Mauldin, M, McAbee, T, McBurney, M, Mccarville, T, McCrory, RL, McEvoy, AM, McGuffey, C, Mcinnis, M, McKenty, P, McKinley, MS, McLeod, JB, McPherson, A, Mcquillan, B, Meamber, M, Meaney, KD, Meezan, NB, Meissner, R, Mehlhorn, TA, Mehta, NC, Menapace, J, Merrill, FE, Merritt, BT, Merritt, EC, Meyerhofer, DD, Mezyk, S, Mich, RJ, Michel, PA, Milam, D, Miller, C, Miller, D, Miller, DS, Miller, E, Miller, EK, Miller, J, Miller, M, Miller, PE, Miller, T, Miller, W, Miller-Kamm, V, Millot, M, Milovich, JL, Minner, P, Miquel, J-L, Mitchell, S, Molvig, K, Montesanti, RC, Montgomery, DS, Monticelli, M, Montoya, A, Moody, JD, Moore, AS, Moore, E, Moran, M, Moreno, JC, Moreno, K, Morgan, BE, Morrow, T, Morton, JW, Moses, E, Moy, K, Muir, R, Murillo, MS, Murray, JE, Murray, JR, Munro, DH, Murphy, TJ, Munteanu, FM, Nafziger, J, Nagayama, T, Nagel, SR, Nast, R, Negres, RA, Nelson, A, Nelson, D, Nelson, J, Nelson, S, Nemethy, S, Neumayer, P, Newman, K, Newton, M, Nguyen, H, Di Nicola, J-MG, Di Nicola, P, Niemann, C, Nikroo, A, Nilson, PM, Nobile, A, Noorai, V, Nora, R, Norton, M, Nostrand, M, Note, V, Novell, S, Nowak, PF, Nunez, A, Nyholm, RA, O'Brien, M, Oceguera, A, Oertel, JA, Okui, J, Olejniczak, B, Oliveira, J, Olsen, P, Olson, B, Olson, K, Olson, RE, Opachich, YP, Orsi, N, Orth, CD, Owen, M, Padalino, S, Padilla, E, Paguio, R, Paguio, S, Paisner, J, Pajoom, S, Pak, A, Palaniyappan, S, Palma, K, Pannell, T, Papp, F, Paras, D, Parham, T, Park, H-S, Pasternak, A, Patankar, S, Patel, MV, Patel, PK, Patterson, R, Patterson, S, Paul, B, Paul, M, Pauli, E, Pearce, OT, Pearcy, J, Pedrotti, B, Peer, A, Pelz, LJ, Penetrante, B, Penner, J, Perez, A, Perkins, LJ, Pernice, E, Perry, TS, Person, S, Petersen, D, Petersen, T, Peterson, DL, Peterson, EB, Peterson, JE, Peterson, JL, 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S, Rosen, M, Rosenberg, M, Ross, G, Ross, JS, Ross, P, Rouse, J, Rovang, D, Rubenchik, AM, Rubery, MS, Ruiz, CL, Rushford, M, Russ, B, Rygg, JR, Ryujin, BS, Sacks, RA, Sacks, RF, Saito, K, Salmon, T, Salmonson, JD, Sanchez, J, Samuelson, S, Sanchez, M, Sangster, C, Saroyan, A, Sater, J, Satsangi, A, Sauers, S, Saunders, R, Sauppe, JP, Sawicki, R, Sayre, D, Scanlan, M, Schaffers, K, Schappert, GT, Schiaffino, S, Schlossberg, DJ, Schmidt, DW, Schmitt, MJ, Schneider, DHG, Schneider, MB, Schneider, R, Schoff, M, Schollmeier, M, Schölmerich, M, Schroeder, CR, Schrauth, SE, Scott, HA, Scott, I, Scott, JM, Scott, RHH, Scullard, CR, Sedillo, T, Seguin, FH, Seka, W, Senecal, J, Sepke, SM, Seppala, L, Sequoia, K, Severyn, J, Sevier, JM, Sewell, N, Seznec, S, Shah, RC, Shamlian, J, Shaughnessy, D, Shaw, M, Shaw, R, Shearer, C, Shelton, R, Shen, N, Sherlock, MW, Shestakov, AI, Shi, EL, Shin, SJ, Shingleton, N, Shmayda, W, Shor, M, Shoup, M, Shuldberg, C, Siegel, L, Silva, FJ, Simakov, AN, Sims, 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AJ, Torres, J, Town, RPJ, Townsend, S, Trenholme, J, Trivelpiece, A, Trosseille, C, Truax, H, Trummer, D, Trummer, S, Truong, T, Tubbs, D, Tubman, ER, Tunnell, T, Turnbull, D, Turner, RE, Ulitsky, M, Upadhye, R, Vaher, JL, VanArsdall, P, VanBlarcom, D, Vandenboomgaerde, M, VanQuinlan, R, Van Wonterghem, BM, Varnum, WS, Velikovich, AL, Vella, A, Verdon, CP, Vermillion, B, Vernon, S, Vesey, R, Vickers, J, Vignes, RM, Visosky, M, Vocke, J, Volegov, PL, Vonhof, S, Von Rotz, R, Vu, HX, Vu, M, Wall, D, Wall, J, Wallace, R, Wallin, B, Walmer, D, Walsh, CA, Walters, CF, Waltz, C, Wan, A, Wang, A, Wang, Y, Wark, JS, Warner, BE, Watson, J, Watt, RG, Watts, P, Weaver, J, Weaver, RP, Weaver, S, Weber, CR, Weber, P, Weber, SV, Wegner, P, Welday, B, Welser-Sherrill, L, Weiss, K, Widmann, K, Wheeler, GF, Whistler, W, White, RK, Whitley, HD, Whitman, P, Wickett, ME, Widmayer, C, Wiedwald, J, Wilcox, R, Wilcox, S, Wild, C, Wilde, BH, Wilde, CH, Wilhelmsen, K, Wilke, MD, Wilkens, H, Wilkins, P, Wilks, SC, Williams, EA, Williams, GJ, Williams, W, Williams, WH, Wilson, DC, Wilson, B, Wilson, E, Wilson, R, Winters, S, Wisoff, J, Wittman, M, Wolfe, J, Wong, A, Wong, KW, Wong, L, Wong, N, Wood, R, Woodhouse, D, Woodruff, J, Woods, DT, Woods, S, Woodworth, BN, Wooten, E, Wootton, A, Work, K, Workman, JB, Wright, J, Wu, M, Wuest, C, Wysocki, FJ, Xu, H, Yamaguchi, M, Yang, B, Yang, ST, Yatabe, J, Yeamans, CB, Yee, BC, Yi, SA, Yin, L, Young, B, Young, CS, Young, CV, Young, P, Youngblood, K, Zacharias, R, Zagaris, G, Zaitseva, N, Zaka, F, Ze, F, Zeiger, B, Zika, M, Zimmerman, GB, Zobrist, T, Zuegel, JD, Zylstra, AB, Indirect Drive ICF Collaboration, Collaboration, Indirect Drive ICF, AWE Plc, Lawrence Livermore National Laboratory, and U.S Department of Energy
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General Physics ,02 Physical Sciences ,General Physics and Astronomy ,Indirect Drive ICF Collaboration ,01 Mathematical Sciences ,09 Engineering - Abstract
For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion.
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- 2022
3. Evolocumab and clinical outcomes in patients with cardiovascular disease
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Sabatine, Marc S., Giugliano, Robert P., Keech, Anthony C., Honarpour, Narimon, Wiviott, Stephen D., Murphy, Sabina A., Kuder, Julia F., Wang, Huei, Liu, Thomas, Wasserman, Scott M., Sever, Peter S., Pedersen, Fish MP, Terje R., Abrahamsen, Te, Im, K, Kanevsky, E, Bonaca, Mp, Lira Pineda, A, Hanlon, K, Knusel, B, Somaratne, R, Kurtz, C, Scott, R, Accini Mendoza JL, Amerena, J, Badariene, J, Burgess, L, Ceska, R, Charng, Mj, Choi, D, Cobos, Jl, Dan, Ga, De Ferrari GM, Deedwania, Pc, Chopra, Vk, Erglis, A, Ezhov, Mv, Ferreira, J, Filipová, S, Gaciong, Za, Pasierski, T, Georgiev, Bg, Gonzalez-Galvez, G, Gouni-Berthold, I, Schäufele, T, Hirayama, A, Huber, K, Rammer, M, Kjaerulf Jensen, H, Wermuth, S, Jiang, L, Jukema, Jw, Kraydashenko, O, Leiter, La, Lewis, Bs, López-Miranda, J, Lorenzatti, Aj, Mach, F, Mcadam, B, Nilsson, L, Olsson, Å, Rallidis, L, Rogelio, Gg, Kerr Saraiva JF, Scheen, A, Schiele, F, Scott, Rs, Connolly, D, Siu, Cw, Tay, L, Thorgeirsson, G, Tikkanen, Mj, Tokgozoglu, Sl, 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Tahirkheli, N, Delgado, E, Derian, W, Greenwald, J, Harris, M, Jackson, R, Marhefka, G, Mcelveen, W, Mooss, A, Morris, P, Murray, J, Pearlstein, P, Raisinghani, A, Rezkalla, S, Sakhrani, L, Schreibman, D, Shaoulian, E, Steinsapir, J, Yataco, A, De La Cruz, A, Fredrick, M, Goldenberg, E, Lee, D, Mccullum, K, Mclellan, B, Stephens, L, Wilson, S, Alfieri, A, Mandviwala, M, Orourke, D, Samal, A, Schmedtje, J, Waxman, F, Carhart, R, Clements, B, Dyke, C, Ghali, J, Gruberg, L, Hack, T, Jehle, A, Pogue, B, Schooley, C, and Shifrin, G
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Male ,STATIN THERAPY ,2700 General Medicine ,Disease ,Cardiovascular ,PLACEBO-CONTROLLED TRIAL ,Gastroenterology ,0302 clinical medicine ,Anticholesteremic Agent ,Medicine ,Myocardial infarction ,11 Medical and Health Sciences ,ddc:616 ,Incidence ,Antibodies, Monoclonal ,General Medicine ,Cholesterol ,Cardiovascular Diseases ,Monoclonal ,Drug Therapy, Combination ,Proprotein Convertase 9 ,Antibody ,Aged ,Anticholesteremic Agents ,Atherosclerosis ,Cholesterol, LDL ,Double-Blind Method ,Female ,Follow-Up Studies ,Humans ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Hypercholesterolemia ,Least-Squares Analysis ,Middle Aged ,Medicine (all) ,REDUCING LIPIDS ,Human ,medicine.medical_specialty ,Evinacumab ,Clinical Trials and Supportive Activities ,PCSK9 INHIBITION ,Follow-Up Studie ,LDL ,03 medical and health sciences ,Drug Therapy ,Clinical Research ,LDL-C ,Least-Squares Analysi ,Science & Technology ,Unstable angina ,PCSK9 ,medicine.disease ,chemistry ,Clinical Biochemistry ,030204 cardiovascular system & hematology ,Bococizumab ,FOURIER Steering Committee and Investigators ,Medical and Health Sciences ,chemistry.chemical_compound ,Antibodies monoclonal ,Cardiovascular Disease ,030212 general & internal medicine ,Stroke ,Humanized ,RISK ,biology ,PCSK9 Inhibitors ,10051 Rheumatology Clinic and Institute of Physical Medicine ,Heart Disease ,Atherosclerosi ,6.1 Pharmaceuticals ,Combination ,Cardiology ,Life Sciences & Biomedicine ,Antibodies, Monoclonal, Humanized ,EZETIMIBE ,610 Medicine & health ,Antibodies ,Medicine, General & Internal ,General & Internal Medicine ,Internal medicine ,CORONARY-HEART-DISEASE ,In patient ,Heart Disease - Coronary Heart Disease ,Alirocumab ,Ldl cholesterol ,business.industry ,Evaluation of treatments and therapeutic interventions ,Evolocumab ,Good Health and Well Being ,Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE ,biology.protein ,MODERATE ,Hydroxymethylglutaryl-CoA Reductase Inhibitor ,business - Abstract
Background Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin–kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol levels by approximately 60%. Whether it prevents cardiovascular events is uncertain. Methods We conducted a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or higher who were receiving statin therapy. Patients were randomly assigned to receive evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The median duration of follow-up was 2.2 years. Results At 48 weeks, the least-squares mean percentage reduction in LDL cholesterol levels with evolocumab, as compared with placebo, was 59%, from a median baseline value of 92 mg per deciliter (2.4 mmol per liter) to 30 mg per deciliter (0.78 mmol per liter) (P
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- 2017
4. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes
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Holman, Rr, Bethel, Ma, Mentz, Rj, Thompson, Vp, Lokhnygina, Y, Buse, Jb, Chan, Jc, Choi, J, Gustavson, Sm, Iqbal, N, Maggioni, Ap, Marso, Sp, Öhman, P, Pagidipati, Nj, Poulter, N, Ramachandran, A, Zinman, B, Hernandez, Af, EXSCEL Study Group, : Califf RM, Patel, R, George, J, Sourij, H, Wong, Yw, Hannan, K, Sellers, Ma, Gottlieb, P, Lavender, P, Leloudis, D, Meadows, Y, Larson, D, Anderson, H, Elkins, M, Stone, A, Tisch, A, Perkins, L, Sanders, K, Campbell, C, Kennedy, I, Heal, P, Masterson, M, Darbyshire, J, Mumtaz, L, Athwal, R, Ferch, A, Batra, P, Durborow, L, Vincent, J, Woodall, A, Flanagan, T, Katona, B, Reicher, B, Pozzi, E, Oulhaj, A, Coleman, R, Rouleau, Jl, Pocock, Sj, Gorelick, F, Mcmurray, J, Riddle, M, Gagel, R, Collier, T, Markovic, T, Kong, Aps, Hian, Sk, Scott, R, Panelo, A, Yoon, Kh, Sheu, W, Sritara, P, Linong, J, Pan, C, Yong, H, Schernthaner, G, Mathieu, C, Tankova, T, Widimsky, P, Hanefeld, M, Keltai, M, Wainstein, J, del Prato, S, Pirags, V, Jakuboniene, N, Kooy, A, Dziemidok, P, Veresiu, Ia, Dreval, Av, Murin, J, Torello, Al, Sattar, N, Parkhomenko, O, Omar, M, Diaz, R, Lopes, R, Lanas, F, Urina Triana, M, Leiva-Pons, Jl, Aguliera, D, Bergenstal, R, Goodman, S, Yale, Jf, Caterson, I, Weng, J, Hu, D, Junbo, G, Zannad, F, Anoop, M, Ambrish, M, Gallegos, Ja, Green, Jb, Akerblom, A, Alexander, K, Al-Khatib, S, Armaganijan, L, Barros, P, Batit, M, Bernacki, G, Bernandez, S, Bloomfield, G, Clausen, E, De Souza Brito, F, Devore, A, Dombrowski, K, Eapen, Z, Gellad, Z, George, D, Guimaraes, P, Halim, S, Harrison, R, Hawes, J, Hess, C, Hyland, K, Jackson, L, Jones, S, Jordan, D, Katz, M, Kong, D, Koshizaka, M, Lakey, W, Leblanc, T, Leonardi, S, Luo, N, Mahaffey, K, Mandawat, A, Mehta, R, Melloni, C, Morse, M, Pagidpati, N, Patel, C, Patel, K, Pokorney, S, Posvic, T, Rao, M, Roe, M, Shah, B, Tillmann, H, Truffa, A, Zazula, A, Zeitler, E, Sicer, M, Ulla, Mr, Maffei, L, Klyver, Mi, Calella, P, Alvarisqueta, A, De La Fuente RL, Aizenberg, D, Roque, F, Cruciani, A, Frechtel, G, Gelersztein, E, Villarino, A, Mallagray, M, Nardone, L, Zaidman, C, Novaretto, L, Bartolacci, I, de Salvo, M, Delcourt, C, Crimmins, D, Jackson, R, O’Neal, D, Colman, P, Jeffries, W, Mah, Pm, Wittert, G, Proietto, J, Amerena, J, Marks, S, Tan, R, Colquhoun, D, Pieber, T, Drexel, H, Prager, R, Schnack, C, Hoppichler, F, Fasching, P, Francesconi, C, Luger, A, Schoenherr, Hr, Ebenbichler, C, Paulweber, B, Shernthaner, G, Verhaegen, A, Vanuytsel, J, Thissen, Jp, e Silva P, Barros, Gonzaga, C, Borges, J, Hissa, M, Rea, R, Rossi, P, Chacra, A, Eliaschewitz, F, Garbelini, B, Felicio, J, Rassi, N, Rossi, F, Nunes dos Santos, M, e Farias F, Bandeira, Lisboa, H, e Forti A, Costa, Saraiva, Jk, Kovacheva, S, Levterov, G, Sheinkova, G, Ilieva, E, Lyubenova, L, Damyanova, V, Gushterova, V, Mincheva, L, Illiev, D, Ivanov, V, Bobeva, R, Nikitov, Z, Shumkova, R, Lefterov, In, Zaharieva, S, Videva, V, Yakov, A, Cheung, S, Elliott, T, Mehta, P, Ross, S, Sigal, R, Woo, V, Jaffer, S, Kuritsky, R, Bell, A, Dumas, R, Gosselin, G, Robitaille, Y, Greenspoon, A, Lochnan, H, Tytus, R, Leiter, L, Pandey, A, Punthakee, Z, Dube, F, Sigalas, J, Pearce, M, Woodford, T, Paul, P, Bourgeois, R, Conway, R, Mazza, G, Hatheway, R, Misterski, J, Raffo, C, Olivares, C, Godoy, J, Potthoff, S, Santibañez, C, Larenas Yanez GJ, Gu, W, Shen, F, Ma, J, Guo, X, Li, Q, Du, Y, Hu, J, Ji, L, Li, Y, Deng, H, Feng, Y, Liu, L, Mu, Y, Ma, C, Qu, S, Wang, J, Wang, Y, Yuan, Z, Zhang, L, Zhou, S, Yang, T, Dong, Y, Liu, D, Coronel Arroyo, J, Perez Amador, G, Botero Lopes, R, Jaramilo, C, Orozco Linares, A, Cure Cure CA, Hernandez Triana, E, Molina de Salazar DI, Marin, Cr, Jaramilo Gomez CJ, Kellinerova, I, Adamkova, V, Krami, P, Brychta, T, Havelkova, J, Pantikova, K, Schoper, F, Pohl, W, Schumm-Draeger, Pm, Julius, U, Tschöpe, D, Hamann, A, Seissler, J, Schellong, S, Rose, L, Becker, B, Linn, T, Oerter, Em, Strotmann, Hj, Mölle, A, Pfutzner, A, Forst, T, Schäufele, T, Mugge, A, Lehrke, M, Meyer-Pannwitt, U, Mehling, H, Simon-Wagner, I, Schenkenberger, I, Busch, K, Hermes, S, Milek, K, Landers, B, Grueneberg, M, Braun, M, Nothroff, J, Kamke, W, Hergdt, G, Duengen, Hd, Kleinertz, K, Kuesters, D, Boenninghoff, Ah, Appel, Kf, Schaefer, A, Bieler, T, Ozaki, R, Luk, Aoy, Chu, Dw, Cheung-Wong, Mm, Siu, Dc, Yan, Bpy, Kung, K, Wong, Sys, Tsang, Cc, Yeung, Vt, Cheung, Bm, Tse, Hf, Hodi, G, Nagy, K, Lippai, J, Takacs, J, Fulop, T, Gaal, Z, Pauker, Z, Foldesi, I, Simon, J, Oroszan, T, Futo, L, Bezzegh, K, Nagy, A, Vandorfi, G, Kiss, J, Kesmarki, N, Kis, E, Papp, A, Kovacs, A, Szakal, I, Palinkas, A, Czegany, Z, Voros, P, Reiber, I, Kerenyi, Z, Dezso, E, Wittman, I, Penzes, J, Ples, Z, Taller, A, Farago, K, Kis, Jt, Zilahi, Z, Molnar, M, Barkai, L, Mileder, M, Szentpeteri, I, Peterfai, E, Lovasz, O, Mosenzon, O, Minuchin, O, Jaffe, A, Vishlitsky, V, Shimon, I, Bashkin, A, Stern, N, Elias, N, Bental, T, Butnaru, A, Lewis, B, Adawi, F, Nseir, W, Klainman, E, Herskovits, T, Cignarelli, M, Rotella, Cm, Ambrosio, G, Pozzilli, P, Genovese, S, Cavarape, A, Salvioni, A, Sokolova, J, Strautina, I, Teterovska, D, Stalte, V, Pastare, S, Leitane, I, Lagzdina, L, Andersone, I, Eglite, R, Stelmane, I, Levinger, A, Barsiene, L, Sulskiene, M, Varanauskiene, E, Danyte, E, Urbanaviciene, E, Urbanavicius, V, Zabuliene, L, Juskiene, R, Velaviciene, A, Kakariekiene, V, Augusteniene, A, Velickiene, D, Lasiene, J, Dauksiene, D, Caponis, J, Tan, At, Ramanathan, L, Hassan, Mra, Tan, F, Ong, Tk, Foo, Sh, Ghani, Ra, Cheah, Wk, Sanchez Mijangos JH, Cabrera Jardines, R, Barrientos Perez, M, Sauque Reyna, L, Alcocer Gamba MA, Villeda Espinosa, E, Tamez Perez HE, De La Garza Hernandez NE, Lopes, Sm, Ramirez Diaz SP, Reyes Sanchez, R, Márquez-Rodriguez, E, Köse, V, Voors-Pette, C, Oldenburg-Ligtenberg, Pc, van Kempen WW, Cox, K, Hoogendyk, J, Swinkels-Diepenmaat, L, Rojas-Lingan, G, Kentgens, S, Schipperen, S, de Valk HW, Swart, H, van Bemmel, B, Hoogslag, Pam, Diamant, M, Serné, Eh, Hamer, A, Wilson, S, Fisher, N, Dixon, P, Chaudhri, O, Crawford, V, Quinn, D, Nirmalaraj, K, Dunn, P, Gillies, J, Cutfield, R, Krebs, J, Helm, C, Kerr, J, Pryke, J, Ebo, G, Denopol, M, Ang, E, Uy, N, Jimeno, C, Mirasoi, R, Paz Pacheco, E, Custodio, M, Nicodemus, N Jr, Catindig, Ea, Magno, M, Tirador, L, Cylkowska, B, Stasinksa, T, Silwinska, T, Sroka, M, Piepiorka, M, Korzeniak, R, Mirecka, H, Zaluska, R, Pupek-Musialik, D, Homenda, W, Grabowska, A, Okopien, B, Niegowska, J, Pogorzelska, H, Mikolajczyk-Swatko, A, Sikorski, M, Sowinski, D, Tahk, Sj, Kim, Yn, Nam, Cw, Rim, Sj, Kim, Cj, Choi, Km, Lee, Ik, Kim, Ij, Namgung, J, Moon, Kw, Kim, Ks, Oh, Bh, Lee, Wy, Choi, Sh, Kim, Es, Moon, S, Mindrescu, Nm, Aron, G, Graur, M, Hancu, N, Mlitaru, C, Nafornita, V, Szilagyi, I, Popa, Ar, Angelescu, Lm, Negrisanu, Gd, Zaharie, Dg, Culman, Mi, Vacaru, G, Munteanu, M, Constantinescu, S, Tivadar, S, Dreval, A, Barbarash, O, Strongin, L, Dogadin, S, Suplotova, L, Izmozherova, N, Marasaev, V, Khokhlov, A, Repin, A, Turova, E, Bondar, I, Samoylova, Y, Sherenkov, A, Smolenskaya, O, Zrahevskiy, K, Koshelskaya, O, Obrezan, A, Dzupina, A, Stevlik, J, Buganova, I, Pella, D, Vinanska, D, Jascur, J, Micko, K, Sosovec, D, Philippiova, A, Olexa, P, Fedacko, J, Selecky, J, Nicolau, J, Mediavilla Garcia, J, Botella Serrano, M, Lecube, A, Arguelles, I, Sabán, J, Gómez Cerezo, F, Soto, A, Bellido, D, Sucunza Alfonso, N, Vendrell Ortega, J, Alvarez, L, Garcia Puig, J, Angustias Quesada, M, Contreras Gilbert, J, Almeida, Ca, Tinahones, Fj, Garcia Ortiz, L, Gómez Marcos MA, Aomar, I, Fernández Balsells, M, Distiller, L, Padayachee, T, Badat, A, Ebrahim, I, Naiker, P, Ranjith, N, Kelfkens, Y, Makan, H, Mogashoa, S, Fulat, M, Carim-Ganey, N, Coetzee, K, Govender, T, Nortje, H, Wilhase, A, Seedat, S, Gani, M, Ellis, G, Rheeder, P, Wing, J, Blignaut, S, Kaplan, H, Lottering, H, Pillai, P, Louw, C, Coetzer, T, Sheu, Whh, Chen, Jf, Yang, Cy, Tseng, St, Wang, Cy, Lai, Wt, Hung, Yj, Hsieh, Ic, Su, Sl, Pei, D, Benjasuratwong, Y, Purewal, T, Milward, A, Dimitropoulos, I, Kumar, S, Barber, T, Wiles, P, Dang, C, Adler, A, Philip, S, Bellary, S, Price, D, Oelbaum, R, Heller, S, Sathayapalan, T, Clark, J, Leese, G, Simpson, H, Kilvert, A, Dawson, A, Hall, T, Takhar, A, Bundy, C, Harvey, P, Maxwell, S, Asamoah-Owusu, Nj, Mcknight, J, Chatterjee, S, Calvert, J, Wright, A, Macrury, S, Macfarlane, D, Johnson, A, Litchfield, J, Field, B, Koval, O, Larin, O, Levchenko, O, Martynyuk, L, Maslyanko, V, Rudyk, I, Suprun, Y, Tseluyko, V, Botsyurko, V, Vatutin, M, Fushtey, I, Grishyna, O, Kuskalo, P, Panina, S, Pererva, L, Prysupa, L, Teliatnikova, Z, Sokolova, L, Vlasenko, M, Berenfus, V, Gyrina, O, Kopytsya, M, Vizir, V, Vayda, M, Shanik, M, Headapohl, D, Pahl, J, Aronoff, S, Bartkowiak, A Jr, Chang, A, Gaudiani, L, Kayne, D, Look, M, Patel, N, Moran, J, Stout, E, Tsao, J, Struble, R, Fishman, N, Rodbard, H, Lucas, K, Dugano-Daphnis, P, Merrick, B, Nadar, V, Severa, L, Sorli, C, Chang, M, Reed, J III, Grunberger, G, Bain, C, Bestermann, W Jr, Morawski, E, White, J, Azizad, M, Ukwade, P, Anekwe, A, Jimenez, A, Weiss, D, Green, S, Overcash, J, Eaton, C, Roseman, H, Soler, N, Mikell, F, Manos, P, Levinson, L, Claxton, E Jr, Weiss, R, Argoud, G, Bickel, L, Wilson, J, Short, B, Webster, B, Mcneill, R, Schnall, A, Force, R, Phillips, L, Bybee, K, Forker, A, Denham, D, Vonderhaar, T, Pullman, J, Kruger, D, Whitehouse, F, Wysham, C, Baron, M, Kravitz, A, Dushkin, H, Manning, Mb, Wine, A, Jaffrani, N, Chadha, C, Sperl-Hillen, J, Busch, R, Estevez, R, Robbins, D, Rassouli, N, Garvey, T, Oparil, S, Eckel, R, Mcdermott, M, Rasouli, N, Mcgill, J, Corder, C, Klonoff, D, Mills, R, Earl, J, Kessel, J, Cuddihy, R, Zimmerman, R, Dayamani, P, Oral, E, Zimering, M, Marks, J, Farnsworth, K, Sugimoto, D, Toth, P, Bhargava, A, Mcguire, D, Rohatgi, A, Davies, M, Peden, E, Wyne, K, Alfonso, L, Seyoum, B, Akpunonu, B, Feinglos, M, Reaven, P, Soule, J, Luttrell, L, Schactman, B, Canadas, R, Boggs, B, Abbott, L, Herring, C, Roberts, L, Hage-Korban, E, Schubart, U, Taylon, A, Tannenbaum, A, Kingsley, J, Lenhard, J, Biscoveanu, M, Cohen, J, Donovan, D, Laferrere, B, Thompson, N, Wade, T, Detweiler, R, Henson, B, White, A, Cavale, A, Ravi, C, Thomas, A, Goodman, H, Kalen, V, Fox, D, Dauber, I, Rizvi, S, Marcus, A, Mulford, M, Higgins, A, Chane, M, Bland, V, Osunkoya, A, Suresh, D, Khan, S, Anastasi, L, Bajaj, M, Eisen, H, Mudaliar, Sr, Powell, S, Carr, K, Tripathy, D, Azad, N, Wakefield, P, Acheatel, R, Bressler, P, Dean, J, El Shahawy, M, Gilbert, J, Haque, I, Humiston, D, Ison, R, Karounos, D, Lillestol, M, Ferrier, N, Labroo, A, Vo, A, D’Agostino, R, Dulin, M, Mcwilliams, A, Hargrove, J, Blumberg, E, Jackson, B, Staniloae, C, Salacata, A, Hidalgo, H Jr, Nicol, P, Digiovanna, M, Soufer, J, Mahabadi, V, Akinboboye, O, Arauz-Pacheco, C, Neutel, J, Dungan, K, Benson, M, Powell, T, Gandy, W, Rovner, S, Berk, M, Khan, A, Ledesma, G, Madu, I, Erickson, B, Radbill, M, Graves, M, Kaczmarek, G, Giep, S, Baldauf, C, Golden, G, Lesh, K, Davis, C, Godbole, N, Kirby, W, Razzaque, N, Bhatt, B, Wilson, M., Internal medicine, ACS - Diabetes & metabolism, and ACS - Microcirculation
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Male ,medicine.medical_specialty ,EXSCEL Study Group ,Injections, Subcutaneous ,030209 endocrinology & metabolism ,Type 2 diabetes ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,Placebo ,Article ,Drug Administration Schedule ,GLP1-agonists ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Interquartile range ,Internal medicine ,Diabetes mellitus ,General & Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,Least-Squares Analysis ,Aged ,Glycated Hemoglobin ,business.industry ,Venoms ,Semaglutide ,Incidence ,Type 2 diabetes, GLP1-agonists, exenatide, cardiovascular effects ,General Medicine ,11 Medical And Health Sciences ,Middle Aged ,medicine.disease ,Surgery ,Albiglutide ,Editorial ,Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,Exenatide ,Dulaglutide ,Female ,business ,Peptides ,cardiovascular effects ,medicine.drug - Abstract
BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P
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- 2017
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5. Ezetimibe added to statin therapy after acute coronary syndromes
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Cannon, Christopher P., Blazing, Michael A., Giugliano, Robert P., Mccagg, Amy, White, Jennifer A., Theroux, Pierre, Darius, Harald, Lewis, Basil S., Ophuis, Ton Oude, Jukema, J. Wouter, De Ferrari, Gaetano M., Ruzyllo, Witold, De Lucca, Paul, Kyungah, Im, Bohula, Erin A., Reist, Craig, Wiviott, Stephen D., Tershakovec, Andrew M., Musliner, Thomas A., Braunwald, Eugene, Califf, Musliner T, Robert M., Tershakovec, A, Gurfinkel, E, Aylward, P, Tonkin, A, Maurer, G, Van de Werf, F, Nicolau, Jc, Theroux, P, Genest, J, Armstrong, P, Corbalan, R, Isaza, D, Spinar, J, Grande, P, Voitk, J, Kesaniemi, A, Bassand, Jp, Farnier, M, Darius, H, Keltai, M, Mathur, A, Mittal, S, Reddy, K, Lewis, B, De Ferrari GM, Ophuis, To, Jukema, J, White, H, Pedersen, T, Britto, F, Ruzyllo, W, Carrageta, M, Duris, T, Dalby, A, Seung, Kb, Lopez-Sendon, J, Dellborg, M, Mach, F, Guneri, S, Parkhomenko, A, Brady, A, Cannon, C, Blazing, M, Ballantyne, C, de Lemos, J, Kleiman, N, Mcguire, Dk, Centeno, E, Casalins, M, Cartasegna, L, Beltrano, Mc, Guerrero, R, Fanuele, M, Berra, F, Egido, J, Colombo, H, Dellatorre, M, Terns, P, Blumberg, E, Reges, P, Azize, G, Ramos, H, Fernandez, R, Carlessi, C, Milesi, R, Schmuck, R, Duronto, E, Procopio, G, Carlevaro, O, Maffeo, H, Beloscar, J, Viso, M, Hominal, M, Castoldi, M, Bluguermann, J, Mauro, D, Macin, S, Cocco, N, Ruiz, N, Ricart, J, Lozada, A, Nani, S, Turri, D, Fernandez, H, Caruso, O, Zarandon, R, Bono, J, Arias, V, Allall, O, Marino, J, Cusimano, S, Schygiel, P, Buzetti, C, Penaloza, N, Berli, M, Worthley, S, Roach, A, Chew, D, Wright, T, Leitch, J, Hicks, E, Rankin, J, Venn-Edmonds, C, Lehman, R, Morrison, H, Shaw, J, Mak, V, Hii, C, Smith, K, Cross, D, Lilwall, L, Nelson, G, Loxton, A, Horowitz, J, Rose, J, Steinwender, C, Leisch, F, Kammler, J, Brussee, H, Zweiker, R, Niederl, E, Weihs, W, Giorgio, G, Lang, I, Drexel, H, Zanolin, D, Hoppe, U, Atzenhofer-Baumgartner, K, Pichler, M, Hainzer, D, Eber, B, Pichler, F, Foeger, B, Wechselberger, T, Mayr, H, Hofer, J, Stockenhuber, F, Warlits, B, Huber, K, Egger, F, Weidinger, F, Ziegler, B, Jirak, P, Metzler, B, Pachinger, O, Wanitschek, M, Auer, J, Grabscheit, G, 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E., Cullen, T., Eisenberg, S., Chronos, N., Allen, R.P., Erickson, B., Mahon, K., Kirby, A., Siegel, C., Stroud, L., Johnson, J., Panchal, V., Pearson, A., Abell, T., De Gregorio, M., Boomer, L., Vahdat, O., VanNatta, B., Long, P., Chalavarya, G., Skatrud, L., Carey, C., Wright, W., Mechem, C., Matthews, B., Adams, A., Vora, K., Wead, J., Koren, M., Gregory, D., El Khadra, M., Peacock, G., Kieval, J., Barron, M., Lewis, D., Grice, R., Bobek, M., Moore, C., Nygaard, T., Fischell, T., Salman, W., Schneider, C., Muhlestein, B., Peeler, D., Chang, D., Todd, A., Chilakamarri, V., Hanley, P., Gelormini, J., Iacona, M.A., Effron, B., Mazzurco, S., Mazzella, M., Wyman, P., Orchard, R., Battin, D., Rezkalla, S., Bishop, C., Sharp, S., Gredler, F., Knap, P., Fadel, M., Saucedo, J., Keng, A., Imburgia, M., Blank, E., Effat, M., Khoury, S., Mardis, R., Baldari, D., Tafuri, L., Mascolo, R., Taylor, D., Mandviwala, M., Khan, W., Mumford, T., Mayer, N., Mitchell, B., Oliver, T., Lombardi, W., Zimmerman, T., Rohrbeck, S., Cooke, L., Craig, M., Mego, D., Griffin, B., Perez, J., LeClerc, K., Addington, J., Aboufakher, R., Ahmed, A., Westecott, B., Steel, K., Hawkins, K., Shah, A., Ward, U., McGreevy, M., Goldberg, R., Prashad, R., McDonough, C., Silver, K., Josephson, R., Witsaman, S., Labib, S., Woodhead, G., Schrank, J., Bell, K., Chandna, H., Holly, D., Bethea, C., Fife, B., Gruberg, L., Singer, A., Ramgadoo, M., Lalonde, T., Morin, R., French, W., Barillas, O., Gradner, G., Kahn, Z., Gress, J., Rocco, D., Thew, S., Stifter, W., Fisher, M., McNamara, J., Kupfer, J., Agocha, A., Cush, S., Jones, S., Whitaker, T., Stover, T., Kumkumian, G., Kent, K., Greenberg, A., Pandey, P., Pytlewski, G., Matsumura, M., Kai, W., Sameshima, S., Thomas, J., MacNicholas, D., Pillai, K., Jones, D., Navas, J.P., Laskoe, B., Patel, P., Fini, G., Minor, S., Shipwash, T., Cabrera-Santamaria, A., Rivera, E., Mincher, L., Jafar, M., Yen, M., Finkle, C., Rahimtoola, A., Severson, L., Labroo, A., Jinich, D., Tam, K., Vogel, C., Aggarwal, R., Zakhary, B., Curtis, S., Lyster, M., Humphrey, K., Lavine, P., Fujise, K., Birnbaum, Y., Allen, J., Kesselbrenner, M., Michel, K., Staniloae, C., Liu, M., Sonel, A., Macioce-Caffas, A., Amidon, T., Leggett, J., Yedinak, S., Gudmundsson, G., Sabharwal, J., Dagefoerde, N., Wu, W., Meyerrose, G., Roongsritong, C., Jenkins, L., Lieberman, S., Sokol, S., Gutierrez, C., Nelson, C., Barrett, J., Hotchkiss, D., Farley, A., Atassi, K., Christy, L., Baig, M., Di Fazio, J., Meengs, M., Thomas, K., Surmitis, J., DeVault, S., Farhat, N., Hulyalkar, A., Riddell, L., Rivera, W., Sheynberg, B., Kobayashi, J., Katsaropoulos, J., Jan, M., Krucoff, M., Paterno, C., Chandrasekaran, S., Curry, R., Cassavar, D., Wheeler, M., McGarvey, J., Schwarz, L., Miller, E., Andrea, B., Carswell, B.S., Lurie, M., Patti, J., Bowden, W., Vasiliauskas, T., Latham, R., Schwartz, B., Bradford, L., Mattleman, S., Wertheimer, J., Goulden, D., Khan, M., Hawkins, B., Ostfeld, R., Mueller, H., Ash, Y., Wilson, V., Bayer, M., Marshall, J., Dobies, D., Dawson, G., Osman, A., Saba, F., Costello, T., Fuentes, F., Underwood, C., Vijay, N., Washam, M., Dietz, W., Glasgow, B., Mukherjee, S., Hinchion, N., Speirs, S., Thornley, A., Lee, K., Movahed, M., Strootman, D., Chernick, R., Parrott, C., Flock, C., Marques, V., Syzmanski, E., Rama, P., Domingo, D., Wu, L., Bauer, B., Dionisopoulos, P., Aggarwal, A., Holcomb, R., Foster, R., Hancock, T., Hargrove, J., Fletcher, A., Stine, R., Bullivant, M., Adams, K., Lohman, J., Klepper, V., Kabour, A., Neidhardt, J., Phillips, W., Tardiff, S., Aji, J., Corut, S., Foster, G., Firek, C., St Goar, F., Sumner, R., Davis, T., Schneider, R., Schneider, W., Villa, A., Desai, V., Chhabra, A., Banks, K., Herzog, W., Burley, T., Quyyumi, A., Smiley, W., Manocha, P., Fishbein, G., Weller, C., Coffman, A., Kim, C., Kedia, A., Firth, B., Rizvi, M., Dahiya, R., Foster, B., Balcells, E., Metzger, D.C., Lester, J., Bissett, J., Fahdi, I., Sides, E.A., Azrin, M., Martin, C., Quick, A., Conaway, D., Garg, M., Schallert, G., Lancaster, L., Mckissick, S., Atieh, M., Garbarino, J., Eisenberg, D., Uusinarkaus, K., Wirtemburg, P., Ellis, J., Cristaldi, J., Berglund, R., Negus, B., Pappas, J., Rocha, R., Nguyen, T., Stone, J., Janosik, D., Labovitz, A., Elmore, N., Dave, R., Loffredo, K., Gabriel, G., Snyder, C., Ahmed, O., Stone, H., Kelley, M., Diffenback, M., Friedman, B., Zirkle, J., Severa, L., Sample, S., Dignen, K., Raisinghani, A., Ben-Yehuda, O., Ghannadian, B., Moscoso, R., Mankowski, J., Boliek, W., Rukavina, M., Davis, W., Ledbetter, S., Handel, F., Mastouri, R., Mahenthiran, J., Foltz, J., Malhotra, V., Jonas, J., Berk, M., Singh, V., Nelson, M., Elsner, G., Gall, J., Kondo, N., Frank, S., Chandraratna, P., Ranasinghe, S., Ebrahimi, R., Treadwell, M., Walters, B., Hughes, L., Kramer, J., Kumar, K., Mente, T., Lachterman, B., Schifferdecker, B., Munshi, K., Sease, D., Waldo, D., Chandler, G., Manns, D., Nahhas, A., Kamalesh, M., Williams, V., Reich, D., Desalca, M., Sharma, S., Liston, M., Gupta, K., Costa, M., Altschuller, A., Lemmertz, K., Shanes, J., Hansen, C., Therrien, M., Mendelson, R., Ramnarine, R., Myers, G., Donovan, C., Klein, M., Fine, D., Owens, S., Murray, C., Ketroser, R., Heifetz, S., Darnell, Z., Touchon, R., Taghizadeh, B., Bohle, D., Norwood, D., Forrest, T., Jackson, S., Shumate, K., Bayles, A., Masroor, M., North, W.K., Fishberg, R., Merveil-Ceneus, B., Butcher, R., Menapace, F., Kilbride, S., Ramabadran, R.S., Loukinen, K., Khalil, J., Ramabadran, R., Walsh, S., Gill, S., Cyncar, R., McLachlan, J., Surakanti, V., Rusterholtz, L., Shoukfeh, F., Stephenson, L., Tsang, M., Nolan, V., Gilchrist, I., Jefferson, D., Feldman, T., Reyes, L., Santos, R., Little, W., Wesley, D., Gharib, W., Mendell, A., Esham, G., Kakavas, P., Whitcomb, C., Book, K., Bazzi, A., Alvarez, J., Cohen, Y., Ayres, T., Rhule, V., Labib, A., Schuler, P., Zughaib, M., Telck, K., Bikkina, M., Turnbull, K., Sharma, T., Orosz, S., Shah, R., Petrino, M., Hughes, M., Hershey, J., Hudock, D., Hui, P., Von Bakonyi, A., Arnold, A., Kappel, D., Pennock, G., Cloud, B., Tucker, K., Harp, L., Hoover, C., Eisenhauer, M., Roth, J., Young, C., Thai, H., Escalante, A., Bautista, J., Gazmuri, R., Nyland, J., Cubeddu, L., DeFranco, A., Dias, D., Fielding, M., Reeves, R., Hermany, P., Meissner-Dengler, S., Evans, M., Flores, E., Tannenbaum, A., McGarr, K., Moran, J., Stout, E., Allred, S., Henderson, D., Crandall, L., Strote, J., Voyles, W., Robeson, D., Bedoya, R., Omar, B., Pettyjohn, F., Revere, C., Coy, K., Margolis, J., Sotolongo, C., Scheffel, M., Munir, A., Shirwany, A., Douglas, L., Girala, R., Humphreys, R., Agarwal, J., Bankowski, D., Watson, R., Bishop, B., Klementowicz, P., Blais, D., Cohen, B., Lobur, E., Dimenna, J., Dempsey, K., Izzo, M., Bondi, L., Carell, E., Eaton, C., Saltiel, F., Grewal, G., Connolly, T., Little, T., Wiegman, P., Gips, S., Held, J., Paraschos, A., Quesada, R., Goudreau, E., Sears, M., Istfan, P., Holt, S., McClung, J., Nguyen, N., Quintana, O., Gottlieb, D., Knutson, T., Barringhaus, K., Lester, F., Sullivan, P., Rodriguez-Ospina, L., Cannon, Cp, Blazing, Ma, Giugliano, Rp, Mccagg, A, White, Ja, Theroux, P, Darius, H, Lewis, B, Ophuis, To, Jukema, Jw, De Ferrari, Gm, Ruzyllo, W, De Lucca, P, Im, K, Bohula, Ea, Reist, C, Wiviott, Sd, Tershakovec, Am, Musliner, Ta, Braunwald, E, Califf, Rm, for the IMPROVE-IT, Investigator, Cianflone, D, Cardiovascular Division (SZG), Brigham and Women's Hospital [Boston], College of Information Science and Engineering, Ritsumeikan University, Montreal Heart Institute (MONTREAL HEART INSTITUTE), Laboratoire des Micro-algues toxiques, Institut Louis Malardé [Papeete] (ILM), Institut de Recherche pour le Développement (IRD)-Institut de Recherche pour le Développement (IRD), Interuniversity Cardiology Institute Netherlands, Institute of Cardiology (WARSAW - Cardiology), Institute of Cardiology, Merck Sharp & Dohme Corp., Merck & Co. Inc, DIPARTIMENTO DI MEDICINA SPECIALISTICA, DIAGNOSTICA E SPERIMENTALE, Facolta' di MEDICINA e CHIRURGIA, AREA MIN. 06 - Scienze mediche, Cannon, C.P., Blazing, M.A., Giugliano, R.P., Mccagg, A., White, J.A., Lewis, B.S., Jukema, J.W., De Lucca, P., Im, K., Bohula, E.A., Reist, C., Wiviott, S.D., Tershakovec, A.M., Musliner, T.A., Braunwald, E., Califf, R.M., for the IMPROVE-IT Investigators [.., C. Rapezzi, ], Other departments, Cannon, Christopher P, Blazing, Michael A., Giugliano, Robert P., Mccagg, Amy, White, Jennifer A., Theroux, Pierre, Darius, Harald, Lewis, Basil S., Ophuis, Ton Oude, Jukema, J. Wouter, De Ferrari, Gaetano M., Ruzyllo, Witold, De Lucca, Paul, Kyungah, Im, Bohula, Erin A., Reist, Craig, Wiviott, Stephen D., Tershakovec, Andrew M., Musliner, Thomas A., Braunwald, Eugene, and Califf, Robert M.
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Male ,Simvastatin ,acute coronary syndrome ,aged ,anticholesteremic agents ,azetidines ,cardiovascular diseases ,cholesterol, ldl ,double-blind method ,drug therapy, combination ,ezetimibe ,female ,humans ,hydroxymethylglutaryl-coa reductase inhibitors ,kaplan-meier estimate ,male ,middle aged ,simvastatin ,triglycerides ,medicine (all ,[SDV]Life Sciences [q-bio] ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,Bococizumab ,Triglyceride ,chemistry.chemical_compound ,0302 clinical medicine ,Azetidine ,Cardiovascular Disease ,Anticholesteremic Agent ,Acute Coronary Syndrome ,Aged ,Anticholesteremic Agents ,Azetidines ,Cardiovascular Diseases ,Cholesterol, LDL ,Double-Blind Method ,Drug Therapy, Combination ,Female ,Humans ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Middle Aged ,Triglycerides ,030212 general & internal medicine ,Medicine (all) ,Research Support, Non-U.S. Gov't ,Hazard ratio ,General Medicine ,Acute Coronary Syndrome, Aged ,Anticholesteremic Agents, Azetidines, Cardiovascular Diseases ,Ezetimibe, Female, Humans ,Male, Middle Aged ,3. Good health ,Multicenter Study ,Editorial ,Cholesterol ,Randomized Controlled Trial ,Combination ,Ezetimibe ,lipids (amino acids, peptides, and proteins) ,Human ,medicine.drug ,medicine.medical_specialty ,Acute Coronary Syndroms ,Urology ,Acute Coronary Syndrome/drug therapy ,Anticholesteremic Agents/adverse effects ,Anticholesteremic Agents/therapeutic use ,Azetidines/adverse effects ,Azetidines/therapeutic use ,Cardiovascular Diseases/epidemiology ,Cardiovascular Diseases/mortality ,Cardiovascular Diseases/prevention & control ,Cholesterol, LDL/blood ,Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects ,Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ,Simvastatin/therapeutic use ,Triglycerides/blood ,NO ,LDL ,03 medical and health sciences ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Drug Therapy ,Internal medicine ,Journal Article ,medicine ,Comparative Study ,Alirocumab ,business.industry ,PCSK9 ,ta3121 ,Lomitapide ,DOENÇAS CARDIOVASCULARES ,Endocrinology ,chemistry ,Statin Therapy ,Hydroxymethylglutaryl-CoA Reductase Inhibitor ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
BACKGROUND: Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known.METHODS: We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke. The median follow-up was 6 years.RESULTS: The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (PCONCLUSIONS: When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit. (Funded by Merck; IMPROVE-IT ClinicalTrials.gov number, NCT00202878.).
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- 2015
6. Interfering with the Chronic Immune Response Rescues Chronic Degeneration After Traumatic Brain Injury
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Erturk, A., primary, Mentz, S., additional, Stout, E. E., additional, Hedehus, M., additional, Dominguez, S. L., additional, Neumaier, L., additional, Krammer, F., additional, Llovera, G., additional, Srinivasan, K., additional, Hansen, D. V., additional, Liesz, A., additional, Scearce-Levie, K. A., additional, and Sheng, M., additional
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- 2016
- Full Text
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7. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes.
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IMPROVE-IT Investigators, Musliner, T., Tershakovec, A., Gurfinkel, E., Aylward, P., Tonkin, A., Maurer, G., Van de Werf, F., Nicolau, J.C., Theroux, P., Genest, J., Armstrong, P., Corbalan, R., Isaza, D., Spinar, J., Grande, P., Voitk, J., Kesaniemi, A., Bassand, J.P., Farnier, M., Darius, H., Keltai, M., Mathur, A., Mittal, S., Reddy, K., Lewis, B., De Ferrari, G.M., Ophuis, T.O., Jukema, J., White, H., Pedersen, T., Britto, F., Ruzyllo, W., Carrageta, M., Duris, T., Dalby, A., Seung, K.B., Lopez-Sendon, J., Dellborg, M., Mach, F., Guneri, S., Parkhomenko, A., Brady, A., Cannon, C., Blazing, M., Ballantyne, C., de Lemos, J., Kleiman, N., McGuire, D.K., Centeno, E., Casalins, M., Cartasegna, L., Beltrano, M.C., Guerrero, R., Fanuele, M., Berra, F., Egido, J., Colombo, H., Dellatorre, M., Terns, P., Blumberg, E., Reges, P., Azize, G., Ramos, H., Fernandez, R., Carlessi, C., Milesi, R., Schmuck, R., Duronto, E., Procopio, G., Carlevaro, O., Maffeo, H., Beloscar, J., Viso, M., Hominal, M., Castoldi, M., Bluguermann, J., Mauro, D., Macin, S., Cocco, N., Ruiz, N., Ricart, J., Lozada, A., Nani, S., Turri, D., Fernandez, H., Caruso, O., Zarandon, R., Bono, J., Arias, V., Allall, O., Marino, J., Cusimano, S., Schygiel, P., Buzetti, C., Penaloza, N., Berli, M., Worthley, S., Roach, A., Chew, D., Wright, T., Leitch, J., Hicks, E., Rankin, J., Venn-Edmonds, C., Lehman, R., Morrison, H., Shaw, J., Mak, V., Hii, C., Smith, K., Cross, D., Lilwall, L., Nelson, G., Loxton, A., Horowitz, J., Rose, J., Steinwender, C., Leisch, F., Kammler, J., Brussee, H., Zweiker, R., Niederl, E., Weihs, W., Giorgio, G., Lang, I., Drexel, H., Zanolin, D., Hoppe, U., Atzenhofer-Baumgartner, K., Pichler, M., Hainzer, D., Eber, B., Pichler, F., Foeger, B., Wechselberger, T., Mayr, H., Hofer, J., Stockenhuber, F., Warlits, B., Huber, K., Egger, F., Weidinger, F., Ziegler, B., Jirak, P., Metzler, B., Pachinger, O., Wanitschek, M., Auer, J., Grabscheit, G., Podczeck-Schweighofer, A., Priesnitz, T., Frank, H., El Allaf, D., Marechal, P., Roosen, J., Joly, E., Lefebvre, P., Arend, C., Sinnaeve, P., De Velder, L., Hellemans, S., Vanhauwaert, B., Van Dorpe, A., Heyse, A., Vantomme, C., Striekwold, H., Van Den Broeck, D., Lancellotti, P., Schoors, D., Lemoine, I., Taeymans, Y., De Wolf, L., Brike, C., Vercauteren, S., Tahon, S., Vervoort, G., Mestdagh, I., Pirenne, B., Cardinal, F., Lips, S., Dujardin, K., Debrouwer, K., Dhooghe, G., Holvoet, G., van de Borne, P., Renard, M., De Clippel, M., Lesseliers, H., Van Miert, N., Saraiva, J., Vicente, C., Rossi, P., Dos Santos, L.B., Duda, N., Tognon, A.P., Serrano, C., Gomes, F.L., Manenti, E.R., Silveira, D.S., Maia, L., Mouco, O.M., Paiva, M., Antonangelo, A., de Souza, J., Lino, E.A., Leães, P., Blacher, M.G., Kormann, A., Ultramari, F.T., Dutra, O., Mendelski, A.M., Morgado, S., Ardito, W., Greque, G., Ardito, R.V., Pimentel Filho, P., Zucchetti, C., Alves, A., Seabra, A.M., Mattos, M., Miranda, L.F., Silva, D., Uehara, R.M., Marin Neto, J., Schmidt, A., Braga, J., Rodrigues, A., Abrantes, J., Pinheiro, L., Bodanese, L., Magedanz, É.H., Piegas, L., Dos Santos, E.S., Wainstein, M., Ribeiro, J., Stein, R., Marino, R., Machado, V.M., Moraes Junior, J., Guimarães, S., da Costa, F.A., Ferraz, R.F., Albuquerque, D., Rocha, R.M., de Carvalho Moreira, R., Dohmann, H., Costantini, C., Tarastchuk, J.C., Coelho, O., Cirillo, W., Sousa, A., Almeira, A.S., Stefanini, E., Silva, F., Teixeira, M., da Cunha, C., Précoma, D., Facchi, T.L., Rupka, D., Thiessen, S., Warnica, J., Smith, B., Della Siega, A., Klinke, P., Nelson, S., Dion, D., Gilbert, N., Hui, W., Kvill, L., Sussex, B., Luther, A., Dupuis, R., Ouimet, F., Pandey, A., Clarus, S., Senaratne, M., Ferdinandis, H., Mukherjee, A., Bozek, B., Vizel, S., Markov, G., Zimmermann, R., Stephens, W., Tremblay, B., Wong, G., Uchida, N., Brossoit, R., Peck, C., Van Kieu, C., Forgione, M., Bata, I., Cossett, J., Kostuk, W., Arnold, M., Bone, C., Grondin, F., Bilodeau, N., Gosselin, G., David, M., Giannoccaro, J., Beresford, P., Polasek, P., Roberts, P., Doucet, M., Beaudry, M., Cheung, S., Cleveland, T., Bhargava, R., McCallum, A., Ma, P., Morrissette, J., Cleveland, D., Chadwyn, D., Nigro, F., Weeks, A., Cryderman, C., Leader, R., Houde, G., Rousseau, S., Pearce, M., Radyk, M., Lonn, E., Magi, A., Lefkowitz, C., Sandrin, F., Coffin, N., Lubelsky, B., Coldwell, J., Habot, J., McPherson, C., De Larochelliere, R., Roy, M., Haichin, R., Barber, C., Bhesania, T., Kitagawa, H., To, T., Donnelly, B., Tymchak, W., Harris, L., Kouz, S., Huynh, T., St Jacques, B., Lamy, A., Rizzo, A., Stein, J., Childs, C., Wong, B., Poirier, R., Gupta, M., Dela Cruz, C., Constance, C., Gauthier, M., Ervin, F., Ouellette, M., Kokis, A., Lemay, C., Kwok, K., Leung, C., Lee, D., Nesmith, J., Renton, J., Syan, G., Turek, M., Hogan, D., Griffin, P., Lipson, A., Winestock, J., Abramson, B., Fogel, A., Gagne, C., Bergeron, J., Clarke, A., Slipp, S., Darcel, I., Carling-Chambers, L., Kannampuzha, P., Pallie, S., Krekorian, S., Vertes, G., Roth, S., Lai, K., Heath, J., Perez, L., Arriagada, G., Castro, P., Villa, F., Rodríguez, M., Ramos, G., Baraona, F., Núñez, A., García, M., Jofre, C., Silva, P., Lamich, R., Yovaniniz, P., Escobar, E., Dussaubat, A., Segura, E., Ramirez, M., Lapostol, C., Palma, A., Encina, L., Zapata, M., Baeza, N., Varela, P., Pérez, L., Jaramillo, C., Ruiz, S., Sanchez, G., Perdomo, I., Manzur, F., Cohen, L.E., Velasquez, J., Arana, C., Alvarez, Y., Triana, M., Balaguera, J., de Salazar, D., Rendon, N., Botero, R., Ruiz, A., Saaibi, J., Medina, J., Jaramillo, M., Calderón, M.J., Delgado, J., Bohorquez, R., Medina, M.F., Herrera, M., Rosales, D., Mendoza, F., Martinez, S., Ternera, A., Castro, R., Baiz, A., Martinez, M., Orozco, A., Suarez, M., Fonseca, Y., Beltran, R., Cepeda, M., Jaramillo, N., Valenzuela, C., Gutierrez, M., Sanchez, A., Vitovec, J., Hlinomaz, O., Poloczek, M., Mayer, O., Veselka, J., Vejvoda, J., Soucek, M., Spac, J., Novobilsky, K., Srp, V., Francek, L., Branny, M., Sknouril, L., Motovska, Z., Rohac, F., Stankova, A., Fiala, T., Holub, M., Zeman, K., Pohludkova, L., Pospisilova, E., Tuma, P., Cihalik, C., Oral, I., Podpera, I., Stepanovova, R., Uricar, M., Solar, M., Pelouch, R., Porzer, M., Grussmannova, K., Stipal, R., Reichert, P., Hradec, J., Kral, J., Sejkova, B., Janek, B., Pitha, J., Linhart, A., Polacek, P., Koeber, L., Clemmensen, P., Hebin, C.H., Schmidt, E., Pedersen, M.S., Roseva-Nielsen, N., Kristensen, K., Bang-Hansen, T., Jensen, J., Laage-Petersen, J., Nielsen, H., Stokholm, E., Thayssen, P., Cappelen, H., Jensen, T., Winther-Friis, B., Klausen, I., Hedegaard, B., May, O., Andersen, M., Bottzauw, J., Lush, A., Markenvard, J., Vestager, K.M., Bronnum-Schou, J., Hempel, H., Petersen, J., Nielsen, A.J., Thomsen, K., Nielsen, T., Nygaard, A., Sykulski, R., Jensen, B.S., Ralfkiaer, N., Gottschalck, H., Rasmussen, S., Pedersen, L.R., Dodt, K., Skovsbøl, M., Andersen, O., Tuxen, C., Meier, A.W., Kristensen, T., Rasmussen, O., Lopez, J., Salazar, D., Sanchez, L., Rosero, F., Penaherrera, E., Duarte, Y.C., Marmol, R., Andrade, G., Guzman, E., Morillo, A., Aug, L., Loogna, I., Laanmets, P., Mustonen, J., Mäntylä, P., Kesäniemi, A., Ukkola, O., Kervinen, H., Juhela, S., Juvonen, J., Toppinen, A., Jarvenpaa, J., Syvanne, M., Svahn, T., Voutilainen, S., Huotari, A., Nikkila, M., Raiskinmäki, S., Kotila, M., Rajala, A., Laukkanen, J., Hiltunen, P., Melin, J., Nyman, K., Luukkonen, J., Kosonen, P., Huttunen, M., Seppänen, V., Airaksinen, J., Juonala, M., Lehto, S., Savolainen, K., Halkosaari, M., Sia, J., Palomaki, A., Luoma, J., Utriainen, S., Valpas, S., Tiensuu, T., Lilleberg, J., Kainulainen, R., Schiele, F., Bassand, J., Meneveau, N., Galinier, M., Jean, M., Martelet, M., Mouallem, J., Elbaz, M., Puel, J., Carrié, D., Coisne, D., Varroud-Vial, N., Jaboureck, O., Dujardin, J., Leroy, F., Mansourati, J., Funck, F., Jourdain, P., Guillard, N., Coviaux, F., Gay, A., Dourmap-Collas, C., Froger-Bompas, C., Paillard, F., Tricot, O., Maquin-Mavier, I., Dubois-Rande, J.L., Pongas, D., Paris, A.P., Delahaye, F., Ovize, M., Benyahya, L., Bonnet, J., Belle, L., Mangin, L., Lafitte, B., Zemour, G., Doux, N., Agraou, B., El Mansour, N., Traisnel, G., El Jarroudi, M., Ohlmann, P., Diadema, B., Escande, M., Legros, G., Demarcq, J.M., Haftel, Y., Alsagheer, S., Dambrine, P., Cottin, Y., Ghostine, S., Caussin, C., Gacem, A., Bouvier, J.M., Poulard, J., Davy, J., Furber, A., Prunier, F., Muenzel, T., Genth-Zotz, S., Appel, K., Kretzschmar, D., Ferrari, M., Terres, W., Uher, T., Schulze, H., Ochs, H., Morbach, S., Duengen, H., Gross, M., Oezcelik, C., Tahirovic, E., Heuer, H., Laschewski, B., Kadel, C., Rahn, G., Steiner, S., Kreuzer, J., Tsoy, I., Zeiher, A., Muegge, A., Hanefeld, C., Boehm, S., Boudriot, E., Hodenberg, E., Lippe, B., Hausdorf, C., Sydow, K., Baldus, S., Schlesner, C., Tiroch, K., Haltern, G., Guelker, H., Wilhelm, J., Dietz, S., Ebelt, H., Buerke, M., Rupprecht, H., Rittgen, J., Schaeufele, T., Meinhardt, G., Schieber, M., Honold, M., Sieprath, S., Nienaber, C., Hacker, J., Butter, C., Lapp, H., Hirn, S., Pauschinger, M., Zahn, R., Scheffler, U., Schaefer, A., Schieffer, B., Tebbe, U., Kriete, M., Mudra, H., Raeder, T., Braun, P., Zeymer, U., Kouraki, K., Reppel, M., Schunkert, H., Weil, J., Olbrich, H., Schwaiger, P., Mueller, O., Blessing, E., Buss, I., Bohlscheid, V., Kaddatz, J., Skowasch, D., Nickenig, G., Twelker, K., Osterhues, H., Varghese, T., Burghard, S., Kaeaeb, S., Klauss, V., Sohn, H.Y., Hauptmann, K., Schulze, M., Gall, K., Felix, S., Doerr, M., Mante, J., Gulba, D., Freick, M., Werner, G., Kleinertz, K., Hobbach, H.P., Halbach, M., Mueller-Ehmsen, J., Mueller, M.E., Mitrovic, V., Peil, A., Laufs, U., vom Dahl, J., Baumanns, S., Scholtz, W., Wiemer, M., Haude, M., Van de Loo, A., Pistorius, K., Schaefer, J., Schwinger, R., Goeing, O., Jung, W., Birkemeyer, R., Lee, W., Kong, S., Yu, C., Chui, K., Merkely, B., Szelényi, Z., Polgár, P., Svab, S., Herczeg, B., Bajcsi, É., Vértes, A., Davidovits, S., Nagy, A., Király, C., Lupkovics, G., Kenéz, A., Poór, F., Takács, J., Kirschner, R., Simonyi, G., Koncz, J., Édes, I., Gergely, S., Katona, A., Nagy, E., Kovács, Z., Gyetvai, I., Salamon, C., Kolman, É., Sitkei, É., Csapó, K., Molnar, K., Mező, I., Sereg, M., Reddy, P., Manjunath, C., Narayanappa, S., Kumar, S., Sinha, N., Kapoor, A., Christopher, J., Reddy, G., Rani, M., Oomman, A., Ramamurthee, K., Kumar, N., Pasha, S.S., Rao, C., Murty, G.S., Chopra, A., Kapila, D., Bali, H., Chattree, K., Hasan, O., Suryaprakash, G., Rao, D., Babu, R., Bhargavi, M., Naik, S., Khan, S., Chopra, V., Sapra, R., Kaul, U., Ghose, T., Menon, R., Battikadi, S., Mullasari, A., Subban, V.K., Dani, S., Iby, M., Chandra, P., Sethi, S., Bhargava, M., Arora, P., Tyagi, G., Padmanabhan, T., Malhotra, S., Talwar, K., Shafiq, N., Kasliwal, R., Bansal, M., Eldar, M., Berger, M., Shechter, M., Atar, S., Roguin, N., Kilimnik, M., Hayek, T., Hamoud, S., Katz, A., Plaev, T., Shotan, A., Vazan, A., Weiss, A., Leibowitz, D., Zimlichman, R., Ben-Aharon, J., Hammerman, H., Dragu, R., Rozenman, Y., Witzling, V., Tzivoni, D., Moriel, M., Halkin, A., Sheps, D., Bogomolny, N., Mosseri, M., Khudyak, Y., Halabi, S., Uziel-Iunger, K., Yuval, R., Shimoni, S., Caspi, A., Botwin, S., Gavish, D., Sandler, A., Pollak, A., Kreisberg, B., Hussein, O., Jabal, K., Henkin, Y., Grosbard, A., Rosenschein, U., Rivlin, E., Zeltser, D., Platner, N., Porter, A., Harel, N., Lishner, M., Elis, A., Karny, M., Fuchs, S., Stein, G., Grossman, E., Gealel, Z., Schlaeffer, F., Liberty, I., Golik, A., Tzuman, O., De Ferrari, G., Pavesi, C., Poggio, L., Damiano, S., Pazzano, A.S., Mennuni, M., Paloscia, L., Mascellanti, M., Piovaccari, G., Grosseto, D., Mascia, F., Vetrano, A., Zingarelli, A., Mazzantini, S., Visconti, L., Terzi, G., Senni, M., Gavazzi, A., Scuri, P., Carmelo, M., De Caterina, R., Conti, M., Novo, S., Graceffa, A., Arvigo, L., Lunetta, M., Filardi, P., Chiariello, M., Scala, O., Pirozzi, E., Musella, F., Moretti, L., Testa, M., Vicentini, A., De Feo, S., Biasucci, L., Cardillo, M.T., Puccioni, E., Galli, M., Menegato, A., Margheri, M., Maresta, A., Gatti, C., Guarini, P., Damiano, M., Golino, P., Porcu, M., Fele, N., Gensini, G., Lombardi, A., Ciuti, G., Bernardi, D., Mariani, P., Paolini, E., Marenzi, G., Moltrasio, M., Terrosu, P., Chessa, P., Guglielmino, G., Miccoli, F., Oldoino, E., Ragni, M., Poli, M., Basso, V., Rapezzi, C., Branzi, A., Gallelli, I., Perna, G., Guazzarotti, F., Marra, S., Usmiani, T., Olivari, Z., Calzolari, D., Santoro, G., Minneci, C., Achilli, A., Nassiacos, D., Sommariva, L., Romeo, F., Fedele, F., Foschi, M.L., Bruno, N., Centurion, C., Patrizi, G., De Maria, E., Gonnelli, S., Vichi, V., Cassadonte, F., Rotella, G., Capucci, A., Villani, G., Gaspardone, A., Ferrante, R., Scollo, V., Pancaldi, L., Saccà, S., Gabrielli, D., Ciliberti, D., Savini, E., Binaghi, G., Di Biase, M., Ieva, R., Fattore, L., Cicia, G., Cavallini, C., Tamburino, C., Sacco, A., Mafrici, A., Di Pasquale, G., Pavesi, P.C., Scioli, R., Lioy, E., Occhiuzzi, E., Matino, M.G., Russo, V., Moscogiuri, M.G., Cuccia, C., Forgione, C., Volpe, M., Palano, F., Branca, G., Rossi, R., Modena, M., Olaru, I.A., Zanini, R., Cianflone, D., Cristell, N., Pantaleoni, M., Guiducci, U., Menozzi, C., Gaddi, O., Fasulo, A., Indolfi, C., Emanuele, V., Guerra, F., Iliceto, S., Marotta, C., Morocutti, G., Presbitero, P., Rossi, M., Bonatti, S., Grieco, A., Chiodi, L., Betti, I., Zuppiroli, A., Fanelli, R., Stanco, G., Azzolini, P., Ruggieri, C., Bocconcelli, P., Airoldi, F., Tavano, D., Brunelli, C., Caso, P., Scalzone, A., Ghigliotti, G., Facciorusso, A., Sim, K., Kiam, O., Chee, K., Bin Ismail, O., Zambahari, R., Ophuis, T., van Nes, E., Werter, C.J., Ophuis, A.J., Troquay, R.P., Hamer, B.J., Lenderink, T., Feld, R.J., van Hessen, M.W., Viergever, E.P., van der Sluis, A., Lok, D.J., Badings, E.A., Nierop, P.R., Danse, I.Y., Hermans, W.R., Holwerda, N.J., Thijssen, H.J., Theunissen, L.J., van der Zwaan, C., Van Den Berg, B.J., Hendriks, I.H., Ronner, E., Withagen, A.J., Dijkshoorn-Giesen, A.H., Ezechiels, J.P., Kuijper, A.F., Den Hartog, F.R., Van Kalmthout, P.M., Buijs, E.M., van der Zeijst, M., Zwart, P.A., Zuidgeest, J.A., van Eck, M., Daniels, M.C., van der Ven-Elzebroek, N., Van 't Hof, A., van Boven, A.J., van der Weerdt, A., Dunselman, P.H., Alings, M.A., van Es, R.F., The, S.H., Gurlek, C., Liem, A.H., van Lennep, H.W., Van Vlies, B., Kalkman, C., Swart, H.P., van der Bij, P., Taverne, R., Ciampricotti, R., van Dam, C., Spierenburg, H., van Ruijven, I., van Kempen, L.H., Willems, F.F., Dirkali, A., Stoel, I., Plomp, J., Veldmeijer, S., Tjeerdsma, G., Nijmeijer, R., Van Hal, J.M., Bartels, G.L., Posma, J.L., Linssen, G.C., Fauser, C.G., Waalewijn, R.A., Groenemeijer, B.E., Pos, L., Fast, J.H., Droste, H.T., Westenburg, J., Veenstra, W., Koolen, J., van Loo, L.W., Smits, W., Milhous, J.G., van Rossum, P., Stuij, S., Scott, R., Richards, A.M., Morrison, Z., Devlin, G., Fisher, R., Stewart, R., Benetar, J., Voss, J., Wong, S., Scott, D., Luke, R., Tang, E., Davidson, L., Hamer, A., Wilson, S., Price, R., Hart, H., Turner, A., Jortveit, J., Calic, S., Gundersen, T., Brunvand, H., Fosse, L., Nygaard, O., Gjellefall, B., Gravdal, S.A., Ringstad, R., Atar, D., Clausen, H., Hysing, J., Arvesen, K., Topper, M., Flagstad, E., Graven, T., Haug, H.H., Dalin, L., Al-Ani, R., Otterstad, J., Ausen, K., Aaser, E., Olufsen, M., Halvorsen, S., Gullestad, L., Stueflotten, W., Waage, K., Stødle, R.M., Hall, C., Aase, O., Nordeng, J., Soyland, E., Fageraas, E.R., Lied, A., Aske, R., Raouf, N., Johansson, J., Herrscher, T., Skogrand, E., Bjornstad, H., Aagnes, I., Arntsen, B.I., Vegsundvaag, J., Skjold, M.E., Velle, H., Aambakk, M.B., Skjetne, O., Byfuglien, A., Rodriguez, J., Galvez, D., Medina, F., Hernandez, H.A., Chavez, V., Morales, R., Huapalla, E., Velasquez, D., Torres, F., Aguirre, O., Yanez, L., Andrade, M., Campos, C., Arce, R., Mogrovejo, W., Osores, F., Bustamante, G., Rodriguez, M., Berrospi, P., Garcia, C., Talledo, M., Navarro, P., Horna, M., Herrera, V., Kadziela, J., Rybicka-Musialik, A., Trusz-Gluza, M., Berger-Kucza, A., Musial, W., Tycinska, A., Gil, R., Gziut, A., Gorny, J., Tyllo, M., Reszka, Z., Mickiewicz-Pawlowska, M., Wrzosek, B., Kosior, J., Staneta, P., Korzeniak, R., Kalarus, Z., Markowicz, E., Miekus, P., Konarzewski, M., Kleinrok, A., Puzniak, M., Grajek, S., Janus, M., Krzyzanowski, M., Hoffmann, A., Muzalewski, P., Polonski, L., Kazik, A., Nowalany-Kozielska, E., Wojciechowska, C., Ponikowski, P., Nawrocka, S., Filipiak, K., Serafin, A., Dubiel, J., Mielecki, W., Ogorek, M., Kopcik, D., Jaworska, K., Skonieczny, G., Kawecka-Jaszcz, K., Bryniarski, L., Tracz, W., Lesniak-Sobelga, A., Jankielewicz, J., Zaluska, R., Trojnar, R., Kawalek, P., Gaciong, Z., Pulkowski, G., Anaszewicz, M., Samul, W., Adamus, J., Cholewa, M., Kubik, L., Szczechowicz, R., Rekosz, J., Kwiatkowska, D., Gajek, J., Mazurek, W., Kominek, M., Siminiak, T., Guzniczak, E., Monteiro, P., Providencia, L., Monteiro, S., Pinho, T., Gavina, C., Sousa, C., Loureiro, J., Ferreira, A.R., Cardoso, A., Araujo, J., Rebolo, I., Catarino, C., Santos, J., Nunes, L.P., Mimoso, J., Marques, N., Leitao, M., Pais, J., Fernandes, A., Diogo, A., Nóbrega, J., Moreira, J.I., Mateus, P., Oliveira, J., Selas, M., Ribeiro, V., Albuquerque, A., Reis, R., Ramos, A., Salazar, F., Nair, D., Ng, C.K., Yeo, D., Wong, A., Funiak, S., Belicova, M., Striezova, I., Krajci, P., Sojka, G., Herman, O., Zemberova, A., Pella, D., Fedacko, J., Banikova, A., Micko, K., Macek, V., Moscovic, M., Vahala, P., Vykoukalova, T., Dzupina, A., Marusakova, M., Stevlik, J., Akubzanova, E., Hatalova, K., Burgess, L., Coetzee, C., Mabin, T., Roos, J., Mohamed, Z., Pillay, T., Corbett, C., Bodenstein, W., Tayob, F., Ebrahim, I., Bolsman, C., Horak, A., Lloyd, E., Pretorius, M., Commerford, P., De 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H., Kelley, M., Diffenback, M., Friedman, B., Zirkle, J., Severa, L., Sample, S., Dignen, K., Raisinghani, A., Ben-Yehuda, O., Ghannadian, B., Moscoso, R., Mankowski, J., Boliek, W., Rukavina, M., Davis, W., Ledbetter, S., Handel, F., Mastouri, R., Mahenthiran, J., Foltz, J., Malhotra, V., Jonas, J., Berk, M., Singh, V., Nelson, M., Elsner, G., Gall, J., Kondo, N., Frank, S., Chandraratna, P., Ranasinghe, S., Ebrahimi, R., Treadwell, M., Walters, B., Hughes, L., Kramer, J., Kumar, K., Mente, T., Lachterman, B., Schifferdecker, B., Munshi, K., Sease, D., Waldo, D., Chandler, G., Manns, D., Nahhas, A., Kamalesh, M., Williams, V., Reich, D., Desalca, M., Sharma, S., Liston, M., Gupta, K., Costa, M., Altschuller, A., Lemmertz, K., Shanes, J., Hansen, C., Therrien, M., Mendelson, R., Ramnarine, R., Myers, G., Donovan, C., Klein, M., Fine, D., Owens, S., Murray, C., Ketroser, R., Heifetz, S., Darnell, Z., Touchon, R., Taghizadeh, B., Bohle, D., Norwood, D., Forrest, T., Jackson, S., Shumate, 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IMPROVE-IT Investigators, Musliner, T., Tershakovec, A., Gurfinkel, E., Aylward, P., Tonkin, A., Maurer, G., Van de Werf, F., Nicolau, J.C., Theroux, P., Genest, J., Armstrong, P., Corbalan, R., Isaza, D., Spinar, J., Grande, P., Voitk, J., Kesaniemi, A., Bassand, J.P., Farnier, M., Darius, H., Keltai, M., Mathur, A., Mittal, S., Reddy, K., Lewis, B., De Ferrari, G.M., Ophuis, T.O., Jukema, J., White, H., Pedersen, T., Britto, F., Ruzyllo, W., Carrageta, M., Duris, T., Dalby, A., Seung, K.B., Lopez-Sendon, J., Dellborg, M., Mach, F., Guneri, S., Parkhomenko, A., Brady, A., Cannon, C., Blazing, M., Ballantyne, C., de Lemos, J., Kleiman, N., McGuire, D.K., Centeno, E., Casalins, M., Cartasegna, L., Beltrano, M.C., Guerrero, R., Fanuele, M., Berra, F., Egido, J., Colombo, H., Dellatorre, M., Terns, P., Blumberg, E., Reges, P., Azize, G., Ramos, H., Fernandez, R., Carlessi, C., Milesi, R., Schmuck, R., Duronto, E., Procopio, G., Carlevaro, O., Maffeo, H., Beloscar, J., Viso, M., Hominal, M., Castoldi, M., Bluguermann, J., Mauro, D., Macin, S., Cocco, N., Ruiz, N., Ricart, J., Lozada, A., Nani, S., Turri, D., Fernandez, H., Caruso, O., Zarandon, R., Bono, J., Arias, V., Allall, O., Marino, J., Cusimano, S., Schygiel, P., Buzetti, C., Penaloza, N., Berli, M., Worthley, S., Roach, A., Chew, D., Wright, T., Leitch, J., Hicks, E., Rankin, J., Venn-Edmonds, C., Lehman, R., Morrison, H., Shaw, J., Mak, V., Hii, C., Smith, K., Cross, D., Lilwall, L., Nelson, G., Loxton, A., Horowitz, J., Rose, J., Steinwender, C., Leisch, F., Kammler, J., Brussee, H., Zweiker, R., Niederl, E., Weihs, W., Giorgio, G., Lang, I., Drexel, H., Zanolin, D., Hoppe, U., Atzenhofer-Baumgartner, K., Pichler, M., Hainzer, D., Eber, B., Pichler, F., Foeger, B., Wechselberger, T., Mayr, H., Hofer, J., Stockenhuber, F., Warlits, B., Huber, K., Egger, F., Weidinger, F., Ziegler, B., Jirak, P., Metzler, B., Pachinger, O., Wanitschek, M., Auer, J., Grabscheit, G., Podczeck-Schweighofer, A., Priesnitz, T., Frank, H., El Allaf, D., Marechal, P., Roosen, J., Joly, E., Lefebvre, P., Arend, C., Sinnaeve, P., De Velder, L., Hellemans, S., Vanhauwaert, B., Van Dorpe, A., Heyse, A., Vantomme, C., Striekwold, H., Van Den Broeck, D., Lancellotti, P., Schoors, D., Lemoine, I., Taeymans, Y., De Wolf, L., Brike, C., Vercauteren, S., Tahon, S., Vervoort, G., Mestdagh, I., Pirenne, B., Cardinal, F., Lips, S., Dujardin, K., Debrouwer, K., Dhooghe, G., Holvoet, G., van de Borne, P., Renard, M., De Clippel, M., Lesseliers, H., Van Miert, N., Saraiva, J., Vicente, C., Rossi, P., Dos Santos, L.B., Duda, N., Tognon, A.P., Serrano, C., Gomes, F.L., Manenti, E.R., Silveira, D.S., Maia, L., Mouco, O.M., Paiva, M., Antonangelo, A., de Souza, J., Lino, E.A., Leães, P., Blacher, M.G., Kormann, A., Ultramari, F.T., Dutra, O., Mendelski, A.M., Morgado, S., Ardito, W., Greque, G., Ardito, R.V., Pimentel Filho, P., Zucchetti, C., Alves, A., Seabra, A.M., Mattos, M., Miranda, L.F., Silva, D., Uehara, R.M., Marin Neto, 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Ieva, R., Fattore, L., Cicia, G., Cavallini, C., Tamburino, C., Sacco, A., Mafrici, A., Di Pasquale, G., Pavesi, P.C., Scioli, R., Lioy, E., Occhiuzzi, E., Matino, M.G., Russo, V., Moscogiuri, M.G., Cuccia, C., Forgione, C., Volpe, M., Palano, F., Branca, G., Rossi, R., Modena, M., Olaru, I.A., Zanini, R., Cianflone, D., Cristell, N., Pantaleoni, M., Guiducci, U., Menozzi, C., Gaddi, O., Fasulo, A., Indolfi, C., Emanuele, V., Guerra, F., Iliceto, S., Marotta, C., Morocutti, G., Presbitero, P., Rossi, M., Bonatti, S., Grieco, A., Chiodi, L., Betti, I., Zuppiroli, A., Fanelli, R., Stanco, G., Azzolini, P., Ruggieri, C., Bocconcelli, P., Airoldi, F., Tavano, D., Brunelli, C., Caso, P., Scalzone, A., Ghigliotti, G., Facciorusso, A., Sim, K., Kiam, O., Chee, K., Bin Ismail, O., Zambahari, R., Ophuis, T., van Nes, E., Werter, C.J., Ophuis, A.J., Troquay, R.P., Hamer, B.J., Lenderink, T., Feld, R.J., van Hessen, M.W., Viergever, E.P., van der Sluis, A., Lok, D.J., Badings, E.A., Nierop, P.R., 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- Abstract
Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known. We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke. The median follow-up was 6 years. The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (P<0.001). The Kaplan-Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin-ezetimibe group, as compared with 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P=0.016). Rates of prespecified muscle, gallbladder, and hepatic adverse effects and cancer were similar in the two groups. When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benef
- Published
- 2015
8. Cytotoxic effects on tumour cell lines of fatty acids from the marine sponge S copalina ruetzleri
- Author
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Biegelmeyer, Renata, primary, Schröder, Rafael, additional, Rambo, Douglas F, additional, Dresch, Roger R, additional, Stout, E Paige, additional, Carraro, João L F, additional, Mothes, Beatriz, additional, Moreira, José C F, additional, Molinski, Tadeusz F, additional, da Frota Junior, Mário L C, additional, and Henriques, Amélia T, additional
- Published
- 2015
- Full Text
- View/download PDF
9. The Off-Treatment Effects of Olpasiran on Lipoprotein(a) Lowering: OCEAN(a)-DOSE Extension Period Results.
- Author
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O'Donoghue ML, Rosenson RS, López JAG, Lepor NE, Baum SJ, Stout E, Gaudet D, Knusel B, Kuder JF, Murphy SA, Wang H, Wu Y, Shah T, Wang J, Wilmanski T, Sohn W, Kassahun H, and Sabatine MS
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Treatment Outcome, Double-Blind Method, Atherosclerosis drug therapy, Atherosclerosis blood, Dicarboxylic Acids, Fatty Acids, Lipoprotein(a) blood, RNA, Small Interfering administration & dosage, Dose-Response Relationship, Drug
- Abstract
Background: Olpasiran, a small interfering RNA (siRNA), blocks lipoprotein(a) (Lp(a)) production by preventing translation of apolipoprotein(a) mRNA. In phase 2, higher doses of olpasiran every 12 weeks (Q12W) reduced circulating Lp(a) by >95%., Objectives: This study sought to assess the timing of return of Lp(a) to baseline after discontinuation of olpasiran, as well as longer-term safety., Methods: OCEAN(a)-DOSE (Olpasiran Trials of Cardiovascular Events And LipoproteiN[a] Reduction-DOSE Finding Study) was a phase 2, dose-finding trial that enrolled 281 participants with atherosclerotic cardiovascular disease and Lp(a) >150 nmol/L to 1 of 4 active doses of olpasiran vs placebo (10 mg, 75 mg, 225 mg Q12W, or an exploratory dose of 225 mg Q24W given subcutaneously). The last dose of olpasiran was administered at week 36; after week 48, there was an extended off-treatment follow-up period for a minimum of 24 weeks., Results: A total of 276 (98.2%) participants entered the off-treatment follow-up period. The median study exposure (treatment combined with off-treatment phases) was 86 weeks (Q1-Q3: 79-99 weeks). For the 75 mg Q12W dose, the off-treatment placebo-adjusted mean percent change from baseline in Lp(a) was -76.2%, -53.0%, -44.0%, and -27.9% at 60, 72, 84, and 96 weeks, respectively (all P < 0.001). The respective off-treatment changes in Lp(a) for the 225 mg Q12W dose were -84.4%, -61.6%, -52.2%, and -36.4% (all P < 0.001). During the extension follow-up phase, no new safety concerns were identified., Conclusions: Olpasiran is a potent siRNA with prolonged effects on Lp(a) lowering. Participants receiving doses ≥75 mg Q12W sustained a ∼40% to 50% reduction in Lp(a) levels close to 1 year after the last dose. (Olpasiran Trials of Cardiovascular Events And LipoproteiN[a] Reduction-DOSE Finding Study [OCEAN(a)-DOSE]; NCT04270760)., Competing Interests: Funding Support and Author Disclosures The OCEAN(a)-DOSE study was funded by Amgen. Dr O’Donoghue has received grant funding through Brigham and Women’s Hospital from Novartis, Amgen, AstraZeneca, and Janssen; and has received honoraria from Novartis, Amgen, AstraZeneca, and Janssen. Dr Rosenson has received institutional grant funding from Amgen, Arrowhead, Lilly, Novartis, and Regeneron; has received consulting fees from Amgen, Arrowhead, CRISPER Therapeutics, Lilly, Novartis, Precision Biosciences, Regeneron, and Ultragenyx; has received nonpromotional speaker fees from Amgen and Kowa; and has held stock in MediMergent. Dr López is an employee of Amgen; and/or has owned Amgen stock or stock options. Dr Lepor has received grant support from Amgen, Novartis, Regeneron, New Amsterdam, Merck, Arrowhead, and AstraZeneca; and has received speaker and/or consulting fees from Amgen, Novartis, Regeneron, Merck, AstraZeneca, and Boehringer Ingelheim. Dr Baum has received consulting fees from Altimmune, Amgen, Axcella, Boehringer Ingelheim, Lilly, Esperion, Ionis, Madrigal, Merck, Novartis, and Regeneron; and has received speaker fees from Amgen, Lilly, and Regeneron. Dr Gaudet has received grants and personal fees from Amgen during the conduct of the study; has received grants from Acasti, Kowa, Uniqure, Sanofi, Aegerion, Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Ceapro, Dalcor, Esperion, Arrowhead, Regeneron, Akcea, Allergan, Amryt, Ionis, Novartis, Novo Nordisk, Pfizer, Lilly, and The Medicine Company, outside the submitted work; and has received personal fees from Arrowhead, Regeneron, Akcea, Allergan, Amryt, Ionis, Novartis, Novo Nordisk, Pfizer, Lilly, CRISPR Therapeutics, Saliogen, and Ceapro, outside the submitted work. Dr Knusel is an employee of Amgen; and/or has owned Amgen stock or stock options. Ms Kuder has served as a member of the TIMI Study Group, which has received institutional research grant support through Brigham and Women’s Hospital from Abbott, Amgen, Anthos Therapeutics, AstraZeneca, Bayer HealthCare Pharmaceuticals, Daiichi-Sankyo, Eisai, Intarcia, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron, Roche, Siemens Healthcare Diagnostics, The Medicines Company, and Zora Biosciences. Ms Murphy has served as a member of the TIMI Study Group, which has received institutional research grant support through Brigham and Women’s Hospital from Abbott, Amgen, Anthos Therapeutics, AstraZeneca, Bayer HealthCare Pharmaceuticals, Daiichi-Sankyo, Eisai, Intarcia, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron, Roche, Siemens Healthcare Diagnostics, The Medicines Company, and Zora Biosciences. Dr H. Wang is an employee of Amgen; and/or has owned Amgen stock or stock options. Dr Wu is an employee of Amgen; and/or has owned Amgen stock or stock options. Dr Shah is an employee of Amgen; and has owned Amgen stock. Dr J. Wang is an employee of Amgen; and has owned Amgen stock. Dr Wilmanski is an employee of Amgen; and has owned Amgen stock. Dr Sohn is an employee of Amgen; and/or has owned Amgen stock or stock options; and has existing or pending patents related to olpasiran. Dr Kassahun is an employee of Amgen; and/or has owned Amgen stock or stock options; and has existing or pending patents related to olpasiran. Dr Sabatine has received research grant support through Brigham and Women’s Hospital from Abbott, Amgen, Anthos Therapeutics, Inc, AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Ionis, Merck, Novartis, Pfizer, Saghmos Therapeutics, and Verve Therapeutics; has served as a consultant for Amgen, AMPEL BioSolutions, Anthos Therapeutics, Inc, AstraZeneca, Beren Therapeutics, Boehringer Ingelheim, Dr Reddy’s Laboratories, Fibrogen, Merck, Moderna, Novo Nordisk, Precision BioSciences, and Silence Therapeutics; and has served as a member of the TIMI Study Group, which has also received institutional research grant support through Brigham and Women’s Hospital from ARCA Biopharma, Janssen Research and Development, Siemens Healthcare Diagnostics, Softcell Medical Limited, Regeneron, Roche, and Zora Biosciences. Dr Stout has reported that he has no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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10. Achievement of Target Gain Larger than Unity in an Inertial Fusion Experiment.
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Abu-Shawareb H, Acree R, Adams P, Adams J, Addis B, Aden R, Adrian P, Afeyan BB, Aggleton M, Aghaian L, Aguirre A, Aikens D, Akre J, Albert F, Albrecht M, Albright BJ, Albritton J, Alcala J, Alday C, Alessi DA, Alexander N, Alfonso J, Alfonso N, Alger E, Ali SJ, Ali ZA, Allen A, Alley WE, Amala P, Amendt PA, Amick P, Ammula S, Amorin C, Ampleford DJ, Anderson RW, Anklam T, Antipa N, Appelbe B, Aracne-Ruddle C, Araya E, Archuleta TN, Arend M, Arnold P, Arnold T, Arsenlis A, Asay J, Atherton LJ, Atkinson D, Atkinson R, Auerbach JM, Austin B, Auyang L, Awwal AAS, Aybar N, Ayers J, Ayers S, Ayers T, Azevedo S, Bachmann B, Back CA, Bae J, Bailey DS, Bailey J, Baisden T, Baker KL, Baldis H, Barber D, Barberis M, Barker D, Barnes A, Barnes CW, Barrios MA, Barty C, Bass I, Batha SH, Baxamusa SH, Bazan G, Beagle JK, Beale R, Beck BR, Beck JB, Bedzyk M, Beeler RG, Beeler RG, Behrendt W, Belk L, Bell P, Belyaev M, Benage JF, Bennett G, Benedetti LR, Benedict LX, Berger RL, Bernat T, Bernstein LA, Berry B, Bertolini L, Besenbruch G, Betcher J, Bettenhausen R, Betti R, Bezzerides B, Bhandarkar SD, Bickel R, Biener J, Biesiada T, Bigelow K, Bigelow-Granillo J, Bigman V, Bionta RM, Birge NW, Bitter M, Black AC, Bleile R, Bleuel DL, Bliss E, Bliss E, Blue B, Boehly T, Boehm K, Boley CD, Bonanno R, Bond EJ, Bond T, Bonino MJ, Borden M, Bourgade JL, Bousquet J, Bowers J, Bowers M, Boyd R, Boyle D, Bozek A, Bradley DK, Bradley KS, Bradley PA, Bradley L, Brannon L, Brantley PS, Braun D, Braun T, Brienza-Larsen K, Briggs R, Briggs TM, Britten J, Brooks ED, Browning D, Bruhn MW, Brunner TA, Bruns H, Brunton G, Bryant B, Buczek T, Bude J, Buitano L, Burkhart S, Burmark J, Burnham A, Burr R, Busby LE, Butlin B, Cabeltis R, Cable M, Cabot WH, Cagadas B, Caggiano J, Cahayag R, Caldwell SE, Calkins S, Callahan DA, Calleja-Aguirre J, Camara L, Camp D, Campbell EM, Campbell JH, Carey B, Carey R, Carlisle K, Carlson L, Carman L, Carmichael J, Carpenter A, Carr C, Carrera JA, Casavant D, Casey A, Casey DT, Castillo A, Castillo E, Castor JI, Castro C, Caughey W, Cavitt R, Celeste J, Celliers PM, Cerjan C, Chandler G, Chang B, Chang C, Chang J, Chang L, Chapman R, Chapman TD, Chase L, Chen H, Chen H, Chen K, Chen LY, Cheng B, Chittenden J, Choate C, Chou J, Chrien RE, Chrisp M, Christensen K, Christensen M, Christiansen NS, Christopherson AR, Chung M, Church JA, Clark A, Clark DS, Clark K, Clark R, Claus L, Cline B, Cline JA, Cobble JA, Cochrane K, Cohen B, Cohen S, Collette MR, Collins GW, Collins LA, Collins TJB, Conder A, Conrad B, Conyers M, Cook AW, Cook D, Cook R, Cooley JC, Cooper G, Cope T, Copeland SR, Coppari F, Cortez J, Cox J, Crandall DH, Crane J, Craxton RS, Cray M, Crilly A, Crippen JW, Cross D, Cuneo M, Cuotts G, Czajka CE, Czechowicz D, Daly T, Danforth P, Danly C, Darbee R, Darlington B, Datte P, Dauffy L, Davalos G, Davidovits S, Davis P, Davis J, Dawson S, Day RD, Day TH, Dayton M, Deck C, Decker C, Deeney C, DeFriend KA, Deis G, Delamater ND, Delettrez JA, Demaret R, Demos S, Dempsey SM, Desjardin R, Desjardins T, Desjarlais MP, Dewald EL, DeYoreo J, Diaz S, Dimonte G, Dittrich TR, Divol L, Dixit SN, Dixon J, Do A, Dodd ES, Dolan D, Donovan A, Donovan M, Döppner T, Dorrer C, Dorsano N, Douglas MR, Dow D, Downie J, Downing E, Dozieres M, Draggoo V, Drake D, Drake RP, Drake T, Dreifuerst G, Drury O, DuBois DF, DuBois PF, Dunham G, Durocher M, Dylla-Spears R, Dymoke-Bradshaw AKL, Dzenitis B, Ebbers C, Eckart M, Eddinger S, Eder D, Edgell D, Edwards MJ, Efthimion P, Eggert JH, Ehrlich B, Ehrmann P, Elhadj S, Ellerbee C, Elliott NS, Ellison CL, Elsner F, Emerich M, Engelhorn K, England T, English E, Epperson P, Epstein R, Erbert G, Erickson MA, Erskine DJ, Erlandson A, Espinosa RJ, Estes C, Estabrook KG, Evans S, Fabyan A, Fair J, Fallejo R, Farmer N, Farmer WA, Farrell M, Fatherley VE, Fedorov M, Feigenbaum E, Fehrenbach T, Feit M, Felker B, Ferguson W, Fernandez JC, Fernandez-Panella A, Fess S, Field JE, Filip CV, Fincke JR, Finn T, Finnegan SM, Finucane RG, Fischer M, Fisher A, Fisher J, Fishler B, Fittinghoff D, Fitzsimmons P, Flegel M, Flippo KA, Florio J, Folta J, Folta P, Foreman LR, Forrest C, Forsman A, Fooks J, Foord M, Fortner R, Fournier K, Fratanduono DE, Frazier N, Frazier T, Frederick C, Freeman MS, Frenje J, Frey D, Frieders G, Friedrich S, Froula DH, Fry J, Fuller T, Gaffney J, Gales S, Le Galloudec B, Le Galloudec KK, Gambhir A, Gao L, Garbett WJ, Garcia A, Gates C, Gaut E, Gauthier P, Gavin Z, Gaylord J, Geddes CGR, Geissel M, Génin F, Georgeson J, Geppert-Kleinrath H, Geppert-Kleinrath V, Gharibyan N, Gibson J, Gibson C, Giraldez E, Glebov V, Glendinning SG, Glenn S, Glenzer SH, Goade S, Gobby PL, Goldman SR, Golick B, Gomez M, Goncharov V, Goodin D, Grabowski P, Grafil E, Graham P, Grandy J, Grasz E, Graziani FR, Greenman G, Greenough JA, Greenwood A, Gregori G, Green T, Griego JR, Grim GP, Grondalski J, Gross S, Guckian J, Guler N, Gunney B, Guss G, Haan S, Hackbarth J, Hackel L, Hackel R, Haefner C, Hagmann C, Hahn KD, Hahn S, Haid BJ, Haines BM, Hall BM, Hall C, Hall GN, Hamamoto M, Hamel S, Hamilton CE, Hammel BA, Hammer JH, Hampton G, Hamza A, Handler A, Hansen S, Hanson D, Haque R, Harding D, Harding E, Hares JD, Harris DB, Harte JA, Hartouni EP, Hatarik R, Hatchett S, Hauer AA, Havre M, Hawley R, Hayes J, Hayes J, Hayes S, Hayes-Sterbenz A, Haynam CA, Haynes DA, Headley D, Heal A, Heebner JE, Heerey S, Heestand GM, Heeter R, Hein N, Heinbockel C, Hendricks C, Henesian M, Heninger J, Henrikson J, Henry EA, Herbold EB, Hermann MR, Hermes G, Hernandez JE, Hernandez VJ, Herrmann MC, Herrmann HW, Herrera OD, Hewett D, Hibbard R, Hicks DG, Higginson DP, Hill D, Hill K, Hilsabeck T, Hinkel DE, Ho DD, Ho VK, Hoffer JK, Hoffman NM, Hohenberger M, Hohensee M, Hoke W, Holdener D, Holdener F, Holder JP, Holko B, Holunga D, Holzrichter JF, Honig J, Hoover D, Hopkins D, Berzak Hopkins LF, Hoppe M, Hoppe ML, Horner J, Hornung R, Horsfield CJ, Horvath J, Hotaling D, House R, Howell L, Hsing WW, Hu SX, Huang H, Huckins J, Hui H, Humbird KD, Hund J, Hunt J, Hurricane OA, Hutton M, Huynh KH, Inandan L, Iglesias C, Igumenshchev IV, Ivanovich I, Izumi N, Jackson M, Jackson J, Jacobs SD, James G, Jancaitis K, Jarboe J, Jarrott LC, Jasion D, Jaquez J, Jeet J, Jenei AE, Jensen J, Jimenez J, Jimenez R, Jobe D, Johal Z, Johns HM, Johnson D, Johnson MA, Gatu Johnson M, Johnson RJ, Johnson S, Johnson SA, Johnson T, Jones K, Jones O, Jones M, Jorge R, Jorgenson HJ, Julian M, Jun BI, Jungquist R, Kaae J, Kabadi N, Kaczala D, Kalantar D, Kangas K, Karasiev VV, Karasik M, Karpenko V, Kasarky A, Kasper K, Kauffman R, Kaufman MI, Keane C, Keaty L, Kegelmeyer L, Keiter PA, Kellett PA, Kellogg J, Kelly JH, Kemic S, Kemp AJ, Kemp GE, Kerbel GD, Kershaw D, Kerr SM, Kessler TJ, Key MH, Khan SF, Khater H, Kiikka C, Kilkenny J, Kim Y, Kim YJ, Kimko J, Kimmel M, Kindel JM, King J, Kirkwood RK, Klaus L, Klem D, Kline JL, Klingmann J, Kluth G, Knapp P, Knauer J, Knipping J, Knudson M, Kobs D, Koch J, Kohut T, Kong C, Koning JM, Koning P, Konior S, Kornblum H, Kot LB, Kozioziemski B, Kozlowski M, Kozlowski PM, Krammen J, Krasheninnikova NS, Krauland CM, Kraus B, Krauser W, Kress JD, Kritcher AL, Krieger E, Kroll JJ, Kruer WL, Kruse MKG, Kucheyev S, Kumbera M, Kumpan S, Kunimune J, Kur E, Kustowski B, Kwan TJT, Kyrala GA, Laffite S, Lafon M, LaFortune K, Lagin L, Lahmann B, Lairson B, Landen OL, Land T, Lane M, Laney D, Langdon AB, Langenbrunner J, Langer SH, Langro A, Lanier NE, Lanier TE, Larson D, Lasinski BF, Lassle D, LaTray D, Lau G, Lau N, Laumann C, Laurence A, Laurence TA, Lawson J, Le HP, Leach RR, Leal L, Leatherland A, LeChien K, Lechleiter B, Lee A, Lee M, Lee T, Leeper RJ, Lefebvre E, Leidinger JP, LeMire B, Lemke RW, Lemos NC, Le Pape S, Lerche R, Lerner S, Letts S, Levedahl K, Lewis T, Li CK, Li H, Li J, Liao W, Liao ZM, Liedahl D, Liebman J, Lindford G, Lindman EL, Lindl JD, Loey H, London RA, Long F, Loomis EN, Lopez FE, Lopez H, Losbanos E, Loucks S, Lowe-Webb R, Lundgren E, Ludwigsen AP, Luo R, Lusk J, Lyons R, Ma T, Macallop Y, MacDonald MJ, MacGowan BJ, Mack JM, Mackinnon AJ, MacLaren SA, MacPhee AG, Magelssen GR, Magoon J, Malone RM, Malsbury T, Managan R, Mancini R, Manes K, Maney D, Manha D, Mannion OM, Manuel AM, Manuel MJ, Mapoles E, Mara G, Marcotte T, Marin E, Marinak MM, Mariscal DA, Mariscal EF, Marley EV, Marozas JA, Marquez R, Marshall CD, Marshall FJ, Marshall M, Marshall S, Marticorena J, Martinez JI, Martinez D, Maslennikov I, Mason D, Mason RJ, Masse L, Massey W, Masson-Laborde PE, Masters ND, Mathisen D, Mathison E, Matone J, Matthews MJ, Mattoon C, Mattsson TR, Matzen K, Mauche CW, Mauldin M, McAbee T, McBurney M, Mccarville T, McCrory RL, McEvoy AM, McGuffey C, Mcinnis M, McKenty P, McKinley MS, McLeod JB, McPherson A, Mcquillan B, Meamber M, Meaney KD, Meezan NB, Meissner R, Mehlhorn TA, Mehta NC, Menapace J, Merrill FE, Merritt BT, Merritt EC, Meyerhofer DD, Mezyk S, Mich RJ, Michel PA, Milam D, Miller C, Miller D, Miller DS, Miller E, Miller EK, Miller J, Miller M, Miller PE, Miller T, Miller W, Miller-Kamm V, Millot M, Milovich JL, Minner P, Miquel JL, Mitchell S, Molvig K, Montesanti RC, Montgomery DS, Monticelli M, Montoya A, Moody JD, Moore AS, Moore E, Moran M, Moreno JC, Moreno K, Morgan BE, Morrow T, Morton JW, Moses E, Moy K, Muir R, Murillo MS, Murray JE, Murray JR, Munro DH, Murphy TJ, Munteanu FM, Nafziger J, Nagayama T, Nagel SR, Nast R, Negres RA, Nelson A, Nelson D, Nelson J, Nelson S, Nemethy S, Neumayer P, Newman K, Newton M, Nguyen H, Di Nicola JG, Di Nicola P, Niemann C, Nikroo A, Nilson PM, Nobile A, Noorai V, Nora RC, Norton M, Nostrand M, Note V, Novell S, Nowak PF, Nunez A, Nyholm RA, O'Brien M, Oceguera A, Oertel JA, Oesterle AL, Okui J, Olejniczak B, Oliveira J, Olsen P, Olson B, Olson K, Olson RE, Opachich YP, Orsi N, Orth CD, Owen M, Padalino S, Padilla E, Paguio R, Paguio S, Paisner J, Pajoom S, Pak A, Palaniyappan S, Palma K, Pannell T, Papp F, Paras D, Parham T, Park HS, Pasternak A, Patankar S, Patel MV, Patel PK, Patterson R, Patterson S, Paul B, Paul M, Pauli E, Pearce OT, Pearcy J, Pedretti A, Pedrotti B, Peer A, Pelz LJ, Penetrante B, Penner J, Perez A, Perkins LJ, Pernice E, Perry TS, Person S, Petersen D, Petersen T, Peterson DL, Peterson EB, Peterson JE, Peterson JL, Peterson K, Peterson RR, Petrasso RD, Philippe F, Phillion D, Phipps TJ, Piceno E, Pickworth L, Ping Y, Pino J, Piston K, Plummer R, Pollack GD, Pollaine SM, Pollock BB, Ponce D, Ponce J, Pontelandolfo J, Porter JL, Post J, Poujade O, Powell C, Powell H, Power G, Pozulp M, Prantil M, Prasad M, Pratuch S, Price S, Primdahl K, Prisbrey S, Procassini R, Pruyne A, Pudliner B, Qiu SR, Quan K, Quinn M, Quintenz J, Radha PB, Rainer F, Ralph JE, Raman KS, Raman R, Rambo PW, Rana S, Randewich A, Rardin D, Ratledge M, Ravelo N, Ravizza F, Rayce M, Raymond A, Raymond B, Reed B, Reed C, Regan S, Reichelt B, Reis V, Reisdorf S, Rekow V, Remington BA, Rendon A, Requieron W, Rever M, Reynolds H, Reynolds J, Rhodes J, Rhodes M, Richardson MC, Rice B, Rice NG, Rieben R, Rigatti A, Riggs S, Rinderknecht HG, Ring K, Riordan B, Riquier R, Rivers C, Roberts D, Roberts V, Robertson G, Robey HF, Robles J, Rocha P, Rochau G, Rodriguez J, Rodriguez S, Rosen MD, Rosenberg M, Ross G, Ross JS, Ross P, Rouse J, Rovang D, Rubenchik AM, Rubery MS, Ruiz CL, Rushford M, Russ B, Rygg JR, Ryujin BS, Sacks RA, Sacks RF, Saito K, Salmon T, Salmonson JD, Sanchez J, Samuelson S, Sanchez M, Sangster C, Saroyan A, Sater J, Satsangi A, Sauers S, Saunders R, Sauppe JP, Sawicki R, Sayre D, Scanlan M, Schaffers K, Schappert GT, Schiaffino S, Schlossberg DJ, Schmidt DW, Schmit PF, Smidt JM, Schneider DHG, Schneider MB, Schneider R, Schoff M, Schollmeier M, Schroeder CR, Schrauth SE, Scott HA, Scott I, Scott JM, Scott RHH, Scullard CR, Sedillo T, Seguin FH, Seka W, Senecal J, Sepke SM, Seppala L, Sequoia K, Severyn J, Sevier JM, Sewell N, Seznec S, Shah RC, Shamlian J, Shaughnessy D, Shaw M, Shaw R, Shearer C, Shelton R, Shen N, Sherlock MW, Shestakov AI, Shi EL, Shin SJ, Shingleton N, Shmayda W, Shor M, Shoup M, Shuldberg C, Siegel L, Silva FJ, Simakov AN, Sims BT, Sinars D, Singh P, Sio H, Skulina K, Skupsky S, Slutz S, Sluyter M, Smalyuk VA, Smauley D, Smeltser RM, Smith C, Smith I, Smith J, Smith L, Smith R, Smith R, Schölmerich M, Sohn R, Sommer S, Sorce C, Sorem M, Soures JM, Spaeth ML, Spears BK, Speas S, Speck D, Speck R, Spears J, Spinka T, Springer PT, Stadermann M, Stahl B, Stahoviak J, Stanley J, Stanton LG, Steele R, Steele W, Steinman D, Stemke R, Stephens R, Sterbenz S, Sterne P, Stevens D, Stevers J, Still CH, Stoeckl C, Stoeffl W, Stolken JS, Stolz C, Storm E, Stone G, Stoupin S, Stout E, Stowers I, Strauser R, Streckart H, Streit J, Strozzi DJ, Stutz J, Summers L, Suratwala T, Sutcliffe G, Suter LJ, Sutton SB, Svidzinski V, Swadling G, Sweet W, Szoke A, Tabak M, Takagi M, Tambazidis A, Tang V, Taranowski M, Taylor LA, Telford S, Theobald W, Thi M, Thomas A, Thomas CA, Thomas I, Thomas R, Thompson IJ, Thongstisubskul A, Thorsness CB, Tietbohl G, Tipton RE, Tobin M, Tomlin N, Tommasini R, Toreja AJ, Torres J, Town RPJ, Townsend S, Trenholme J, Trivelpiece A, Trosseille C, Truax H, Trummer D, Trummer S, Truong T, Tubbs D, Tubman ER, Tunnell T, Turnbull D, Turner RE, Ulitsky M, Upadhye R, Vaher JL, VanArsdall P, VanBlarcom D, Vandenboomgaerde M, VanQuinlan R, Van Wonterghem BM, Varnum WS, Velikovich AL, Vella A, Verdon CP, Vermillion B, Vernon S, Vesey R, Vickers J, Vignes RM, Visosky M, Vocke J, Volegov PL, Vonhof S, Von Rotz R, Vu HX, Vu M, Wall D, Wall J, Wallace R, Wallin B, Walmer D, Walsh CA, Walters CF, Waltz C, Wan A, Wang A, Wang Y, Wark JS, Warner BE, Watson J, Watt RG, Watts P, Weaver J, Weaver RP, Weaver S, Weber CR, Weber P, Weber SV, Wegner P, Welday B, Welser-Sherrill L, Weiss K, Wharton KB, Wheeler GF, Whistler W, White RK, Whitley HD, Whitman P, Wickett ME, Widmann K, Widmayer C, Wiedwald J, Wilcox R, Wilcox S, Wild C, Wilde BH, Wilde CH, Wilhelmsen K, Wilke MD, Wilkens H, Wilkins P, Wilks SC, Williams EA, Williams GJ, Williams W, Williams WH, Wilson DC, Wilson B, Wilson E, Wilson R, Winters S, Wisoff PJ, Wittman M, Wolfe J, Wong A, Wong KW, Wong L, Wong N, Wood R, Woodhouse D, Woodruff J, Woods DT, Woods S, Woodworth BN, Wooten E, Wootton A, Work K, Workman JB, Wright J, Wu M, Wuest C, Wysocki FJ, Xu H, Yamaguchi M, Yang B, Yang ST, Yatabe J, Yeamans CB, Yee BC, Yi SA, Yin L, Young B, Young CS, Young CV, Young P, Youngblood K, Yu J, Zacharias R, Zagaris G, Zaitseva N, Zaka F, Ze F, Zeiger B, Zika M, Zimmerman GB, Zobrist T, Zuegel JD, and Zylstra AB
- Abstract
On December 5, 2022, an indirect drive fusion implosion on the National Ignition Facility (NIF) achieved a target gain G_{target} of 1.5. This is the first laboratory demonstration of exceeding "scientific breakeven" (or G_{target}>1) where 2.05 MJ of 351 nm laser light produced 3.1 MJ of total fusion yield, a result which significantly exceeds the Lawson criterion for fusion ignition as reported in a previous NIF implosion [H. Abu-Shawareb et al. (Indirect Drive ICF Collaboration), Phys. Rev. Lett. 129, 075001 (2022)PRLTAO0031-900710.1103/PhysRevLett.129.075001]. This achievement is the culmination of more than five decades of research and gives proof that laboratory fusion, based on fundamental physics principles, is possible. This Letter reports on the target, laser, design, and experimental advancements that led to this result.
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- 2024
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11. Small Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease.
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O'Donoghue ML, Rosenson RS, Gencer B, López JAG, Lepor NE, Baum SJ, Stout E, Gaudet D, Knusel B, Kuder JF, Ran X, Murphy SA, Wang H, Wu Y, Kassahun H, and Sabatine MS
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- Humans, Cardiovascular Diseases drug therapy, Double-Blind Method, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Liver drug effects, Liver metabolism, PCSK9 Inhibitors therapeutic use, Ezetimibe therapeutic use, Anticholesteremic Agents administration & dosage, Anticholesteremic Agents adverse effects, Anticholesteremic Agents pharmacology, Anticholesteremic Agents therapeutic use, Atherosclerosis drug therapy, Hypercholesterolemia drug therapy, Lipoprotein(a) analysis, Lipoprotein(a) antagonists & inhibitors, RNA, Small Interfering administration & dosage, RNA, Small Interfering adverse effects, RNA, Small Interfering pharmacology, RNA, Small Interfering therapeutic use
- Abstract
Background: Lipoprotein(a) is a presumed risk factor for atherosclerotic cardiovascular disease. Olpasiran is a small interfering RNA that reduces lipoprotein(a) synthesis in the liver., Methods: We conducted a randomized, double-blind, placebo-controlled, dose-finding trial involving patients with established atherosclerotic cardiovascular disease and a lipoprotein(a) concentration of more than 150 nmol per liter. Patients were randomly assigned to receive one of four doses of olpasiran (10 mg every 12 weeks, 75 mg every 12 weeks, 225 mg every 12 weeks, or 225 mg every 24 weeks) or matching placebo, administered subcutaneously. The primary end point was the percent change in the lipoprotein(a) concentration from baseline to week 36 (reported as the placebo-adjusted mean percent change). Safety was also assessed., Results: Among the 281 enrolled patients, the median concentration of lipoprotein(a) at baseline was 260.3 nmol per liter, and the median concentration of low-density lipoprotein cholesterol was 67.5 mg per deciliter. At baseline, 88% of the patients were taking statin therapy, 52% were taking ezetimibe, and 23% were taking a proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor. At 36 weeks, the lipoprotein(a) concentration had increased by a mean of 3.6% in the placebo group, whereas olpasiran therapy had significantly and substantially reduced the lipoprotein(a) concentration in a dose-dependent manner, resulting in placebo-adjusted mean percent changes of -70.5% with the 10-mg dose, -97.4% with the 75-mg dose, -101.1% with the 225-mg dose administered every 12 weeks, and -100.5% with the 225-mg dose administered every 24 weeks (P<0.001 for all comparisons with baseline). The overall incidence of adverse events was similar across the trial groups. The most common olpasiran-related adverse events were injection-site reactions, primarily pain., Conclusions: Olpasiran therapy significantly reduced lipoprotein(a) concentrations in patients with established atherosclerotic cardiovascular disease. Longer and larger trials will be necessary to determine the effect of olpasiran therapy on cardiovascular disease. (Funded by Amgen; OCEAN[a]-DOSE ClinicalTrials.gov number, NCT04270760.)., (Copyright © 2022 Massachusetts Medical Society.)
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- 2022
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12. Supporting a public health approach to suicide prevention: Recommendations for state infrastructure.
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Quinlan K, Nickerson K, Ebin J, Humphries-Wadsworth T, Stout E, and Frankini E
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- Humans, Leadership, Public Health, Suicide Prevention
- Abstract
The U.S. National Strategy for Suicide Prevention calls for states to identify supportive structures that encourage efficient, effective, and sustainable suicide prevention programming at the state, territorial, tribal, and local levels (HHS & Action Alliance, 2012). To meet this objective, the Suicide Prevention Resource Center (SPRC) completed a literature review and environmental scan, convened an advisory panel of suicide prevention experts, and conducted interviews with suicide prevention and policy experts to identify six essential state-level infrastructure elements: Authorize-Designate a lead organization for suicide prevention in the state and give it the resources to put a state plan into practice. Lead-Maintain a dedicated leadership and core staff positions in order to enact the plan. Create collaboration within state government. Partner-Ensure a state-level public-private partnership with a shared vision for suicide prevention. Examine-Encourage the collection and analysis of high-quality suicide data. Build-Support a multifaceted lifespan approach to suicide prevention across the state. Guide-Build state and local capacity for prevention. In this commentary, we recommend a framework for organizing an emerging evidence base on the infrastructure and systems that are needed to support an effective, sustainable, public health approach to suicide prevention., (© 2020 The American Association of Suicidology.)
- Published
- 2021
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13. Carbon dioxide (CO 2 ) laser ablation treatment of a peri-urethral genital wart: A case report.
- Author
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Gutierrez P, Garza J, Gandhi K, Voice A, Stout E, and Ventolini G
- Abstract
Background: Visible genital warts are caused by the nearly 100 recognized strains of human papillomavirus (HPV). HPV infections caused by high-risk strains are associated with significant morbidity and mortality rates. Genital warts are diagnosed by visual inspection and treated by three major methods: topical agents, systemic agents, and surgical therapies. CO
2 laser ablation is the best treatment option for warts that present as refractory, thick, extensive lesions. CO2 ablation offers benefits such as a painless procedure, increased clearance rate, lesser side-effects and decreased pain., Case Presentation: An 18-year old patient was referred to the obstetric/gynecology clinic and presented with severe urinary complications. She complained of dysuria, frequency, vaginal irritation, and spraying while voiding. Physical exam was within normal limits; however, genital examination revealed a 3 cm fungating mass corresponding to a large genital wart at the urethral meatus and peri-urethral area. Due to her progressing symptomatology, CO2 laser ablation therapy was advised., Discussion: HPV directly impacts the public health system, affecting 1% of the US population with an estimated 10-20% prevalence rate. Treatment options such as CO2 laser ablation offers complete removal for most patients with limited side-effects. Accurate follow-up is necessary to monitor proper recovery., Conclusion: CO2 laser ablation is considered an effective form of therapy in cases where immediate removal is desired and surgical excision is not recommended. CO2 laser ablation provides high clearance rates and minimal instances of recurrence, as well as superior aesthetic outcome., (© 2020 The Authors. Published by Elsevier B.V.)- Published
- 2020
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14. EVALUATION OF A PARTIALLY REVERSIBLE IMMOBILIZATION PROTOCOL USING MEDETOMIDINE, BUTORPHANOL, ZOLAZEPAM-TILETAMINE, AND KETAMINE IN FREE-RANGING WARTHOGS ( PHACOCHOERUS AFRICANUS ) IN KRUGER NATIONAL PARK, SOUTH AFRICA.
- Author
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Hewlett J, Buss P, Olea-Popelka F, Koeppel K, Neiffer D, Hausler G, Rossouw L, Manamela T, Stout E, and Miller M
- Subjects
- Anesthesia methods, Animals, Animals, Wild, Butorphanol administration & dosage, Drug Combinations, Female, Ketamine administration & dosage, Male, Medetomidine administration & dosage, Parks, Recreational, South Africa, Tiletamine administration & dosage, Zolazepam administration & dosage, Analgesics administration & dosage, Anesthesia veterinary, Anesthetics administration & dosage, Immobilization veterinary, Swine physiology
- Abstract
Twenty-one free-ranging warthogs ( Phacochoerus africanus ) in the Kruger National Park, South Africa, were immobilized with a combination of medetomidine (0.07 ± 0.01 mg/kg), butorphanol (0.26 ± 0.04 mg/kg), tiletamine-zolazepam (0.69 ± 0.15 mg/kg), and ketamine (1.43 ± 0.21 mg/kg) administered intramuscularly by dart. Induction, immobilization, and recovery characteristics were evaluated using a standardized scoring system. In the immobilized warthogs, physiological variables were measured every 5 min and arterial blood gases were analyzed at 15-min intervals. At 45 min after initial drug administration, atipamezole (0.34 ± 0.050 mg/kg) and naltrexone (0.53 ± 0.079 mg/kg) were administered intravenously. Overall, induction quality after darting was scored as excellent and the mean time to safe handling was 5.9 ± 2.0 min. Based on muscle relaxation, and loss of palpebral and pedal reflexes, most subjects (17 out of 21) reached a plane of surgical anesthesia by 10 and 15 min; 20 out of 21 warthogs were in this plane for the duration of the monitoring period. In the immobilized warthogs the overall mean heart rate was 65 ± 15.3 beats per minute, mean respiratory rate was 14.7 ± 5.6 breaths per minute, and the mean rectal temperature was 37.9 ± 1.4°C during the 40 min. Arterial blood gas results showed hypoxemia (mean PaO
2 62.1 ± 16.2 mmHg), hypercapnia (mean PaCO2 47.1 ± 5.1 mmHg), and acidemia (mean pH = 7.36 ± 0.04). Values for PaO2 and pH improved over the immobilization period. After antagonist administration, overall recovery quality from immobilization was scored as good, with animals standing at a mean time of 7.3 ± 4.9 min. The drug combination proved to be effective in the immobilization of free-ranging warthogs with rapid induction, good anesthesia, and limited cardiorespiratory changes. This anesthetic protocol produces effective, safe, and partially reversible immobilization in warthogs.- Published
- 2020
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15. Deaf ACCESS: Adapting Consent Through Community Engagement and State-of-the-Art Simulation.
- Author
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Anderson ML, Riker T, Hakulin S, Meehan J, Gagne K, Higgins T, Stout E, Pici-D'Ottavio E, Cappetta K, and Wolf Craig KS
- Subjects
- Adult, Biomedical Research ethics, Biomedical Research methods, Female, Focus Groups, Humans, Male, Middle Aged, Patient Selection ethics, Pilot Projects, Research Personnel education, Community Participation methods, Community Participation psychology, Deafness psychology, Informed Consent psychology
- Abstract
One of the most understudied health disparity populations in the United States is the Deaf community, a sociolinguistic minority group of more than 500,000 individuals who communicate via American Sign Language. Research on Deaf health disparities is lacking due to inaccessible recruitment, sampling, and data collection procedures, as well as the fundamental disconnect between medical and cultural views of Deaf people. A potential starting place for addressing inaccessible research methods and mistrust of the biomedical research community is the careful reconsideration of the traditional informed consent process, often a Deaf individual's first point of contact with the research world. Yet, most Deaf individuals experience obstacles to engaging in informed consent due to differences in language and development compared to hearing individuals. In response to these issues, our team led a three-phase, formative, community-engaged approach to adapt the informed consent process and train research staff in the updated method so that all required components are properly communicated and understood. The goals of our work were to promote Deaf engagement in research about the Deaf community, increase the number of Deaf individuals who participate in general population biomedical research, and generalize our findings to improve research accessibility for the general population., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2020
- Full Text
- View/download PDF
16. CLINICAL CONDITIONS FOUND RADIOGRAPHICALLY IN THE FRONT FEET OF RETICULATED GIRAFFE ( GIRAFFA CAMELOPARDALIS RETICULATA ) IN A SINGLE ZOO.
- Author
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Dadone L, Olea-Popelka F, Stout E, Foxworth S, Klaphake E, Johnston MS, Han S, and Barrett M
- Subjects
- Aging, Animals, Animals, Zoo, Foot Diseases diagnostic imaging, Fractures, Bone diagnostic imaging, Fractures, Bone veterinary, Osteitis diagnostic imaging, Osteitis veterinary, Foot Diseases veterinary, Giraffes
- Abstract
Front foot radiographs from 22 giraffe ( Giraffa camelopardalis reticulata ) at one zoo were analyzed to better understand causes of lameness in this giraffe population. The herd had a history of front hoof overgrowth and intermittent lameness. Radiographic findings included distal interphalangeal joint osteoarthritis (OA), distal phalangeal bone (P3) osteitis, P3 fractures, P3 rotation, and sesamoid bone cysts. OA of the distal interphalangeal joint occurred in at least one front foot of 73% (16/22 giraffe) of the herd, and all giraffe had OA by 7 yr of age. Pedal osteitis was present in at least one front foot in 86% (19/22) of the giraffe, starting in animals as young as 1 yr old. P3 fractures were present in 36% (8/22) of the herd. These fractures were near the site of the deep digital flexor attachment and were diagnosed in giraffe as young as 10 yr old. The presence of severe osteitis was associated with the presence of P3 fractures. This study is unique in that a large herd was trained to participate in voluntary front foot radiographs so multiple causes of foot disease could be diagnosed antemortem and without anesthesia. Although the underlying causes of these lesions are likely multifactorial and currently unknown to us, the high prevalence of foot disease in relatively young animals warrants further investigation across zoos. In this study, OA, osteitis, and P3 fractures were common radiographic findings among giraffe that were limping. Subsequent monitoring and management changes suggest that proactive management of foot health can decrease morbidity and mortality in zoo giraffe.
- Published
- 2019
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17. MYCOBACTERIUM BOVIS IN FREE-RANGING LIONS ( PANTHERA LEO ) - EVALUATION OF SEROLOGICAL AND TUBERCULIN SKIN TESTS FOR DETECTION OF INFECTION AND DISEASE.
- Author
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Miller MA, Buss P, Sylvester TT, Lyashchenko KP, deKlerk-Lorist LM, Bengis R, Hofmeyr M, Hofmeyr J, Mathebula N, Hausler G, Helden PV, Stout E, Parsons SDC, and Olea-Popelka F
- Subjects
- Animals, Prevalence, Seroepidemiologic Studies, South Africa epidemiology, Tuberculin Test veterinary, Tuberculosis diagnosis, Tuberculosis epidemiology, Lions, Mycobacterium bovis isolation & purification, Tuberculosis veterinary
- Abstract
Bovine tuberculosis (bTB), caused by Mycobacterium bovis infection, causes morbidity and mortality in free-ranging lions in bTB-endemic areas of South Africa. However, the only currently used diagnostic test is the tuberculin skin test (TST). This test is logistically challenging to perform because it requires immobilization of lions twice in a 72-hr period. Blood-based diagnostic tests, such as serological assays, have been previously reported for M. bovis detection in lion populations, and have the advantage of only requiring a single immobilization. In addition, serological assays can be used for retrospective testing. Therefore, the aim of this study was to test free-ranging lions with the STAT-PAKt (Chembio Diagnostics Systems, Medford, NY 11763, USA) and DPPt VetTB (Chembio Diagnostics Systems) serological assays and compare those results with the tuberculin skin test. The serological assays were also used to determine prevalence in bTB-endemic and uninfected lion populations. The results showed that the serological assays could distinguish between M. bovis culture-positive and -negative lions. In addition, antigen-specific humoral responses were present in lions that had clinical signs of bTB disease or were shedding M. bovis antemortem. Although the seroprevalence of M. bovis infection in Kruger National Park lions was similar to that obtained from antemortem mycobacterial culture (4.8 and 3.3%, respectively), it was less than that estimated by the TST (72%). These findings support the hypothesis that assays based on cell-mediated immune responses are more sensitive than serology is in detecting M. bovis infection in lions. However, serological assays can have a role in bTB disease detection in lions and are especially useful for retrospective studies., (© 2019 by American Association of Zoo Veterinarians.)
- Published
- 2019
- Full Text
- View/download PDF
18. Specific Labeling and Lineage Tracing of Periportal Hepatocytes Using Two-Step Genetic Recombination.
- Author
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de Prisco N, Stout E, and Font-Burgada J
- Subjects
- Animals, Cell Differentiation, Cell Lineage, Cell Proliferation, Disease Models, Animal, Down-Regulation, Female, Hepatocytes metabolism, Liver cytology, Liver metabolism, Liver Regeneration, Male, Mice, Stem Cells metabolism, Hepatocytes cytology, Liver injuries, Recombination, Genetic, SOX9 Transcription Factor metabolism, Stem Cells cytology
- Abstract
The liver is unmatched in regenerative capacity. However, when exhausted, the liver is predisposed to various diseases based on injury types and causal agents. Although hepatocytes have been proposed to be the main source of new hepatocytes during regeneration, the existence of specialized liver stem cells has been long debated. In mice, oval cells or ductal cells have been postulated as such stem/progenitor pool. Exhaustive works from different laboratories have shown that in genetically unmodified mice, oval cells, or by extension ductal cells, only contribute marginally in producing new hepatocytes during liver regeneration, thus indicating that hepatocytes are the main regenerative cell source. In this debated context, we identified a new population of periportal hepatocytes in the normal mouse liver. These cells we termed hybrid hepatocytes (HybHP) express low levels of the transcription factor Sox9. Using complementary lineage tracing tools, we demonstrated that HybHP regenerate the liver after chronic hepatocyte depleting injuries. Here, we describe the two-step genetic recombination method that allowed us to study HybHP's lineage in two established models of liver injury.
- Published
- 2019
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- View/download PDF
19. Deaf Qualitative Health Research: Leveraging Technology to Conduct Linguistically and Sociopolitically Appropriate Methods of Inquiry.
- Author
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Anderson ML, Riker T, Gagne K, Hakulin S, Higgins T, Meehan J, Stout E, Pici-D'Ottavio E, Cappetta K, and Wolf Craig KS
- Subjects
- Cultural Competency, Health Literacy, Humans, Politics, Sign Language, Socioeconomic Factors, United States, Community-Based Participatory Research organization & administration, Persons With Hearing Impairments, Qualitative Research, Research Design
- Abstract
One of the most understudied health disparity populations in the United States is the Deaf community-a sociolinguistic minority group of at least 500,000 individuals who communicate using American Sign Language. Research within this population is lacking, in part, due to researchers' use of methodologies that are inaccessible to Deaf sign language users. Traditional qualitative methods were developed to collect and analyze participants' spoken language. There is, therefore, a paradigm shift that must occur to move from an auditory data schema to one that prioritizes the collection and analysis of visual data. To effectively navigate this shift when working with Deaf sign language users, there are unique linguistic and sociopolitical considerations that should be taken into account. The current article explores these considerations and outlines an emerging method of conducting qualitative analysis that, we argue, has the potential to enhance qualitative researchers' work regardless of the population of focus.
- Published
- 2018
- Full Text
- View/download PDF
20. Human axial progenitors generate trunk neural crest cells in vitro.
- Author
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Frith TJ, Granata I, Wind M, Stout E, Thompson O, Neumann K, Stavish D, Heath PR, Ortmann D, Hackland JO, Anastassiadis K, Gouti M, Briscoe J, Wilson V, Johnson SL, Placzek M, Guarracino MR, Andrews PW, and Tsakiridis A
- Subjects
- Biomarkers, Cells, Cultured, Humans, Cell Differentiation, Neural Crest physiology, Pluripotent Stem Cells physiology
- Abstract
The neural crest (NC) is a multipotent embryonic cell population that generates distinct cell types in an axial position-dependent manner. The production of NC cells from human pluripotent stem cells (hPSCs) is a valuable approach to study human NC biology. However, the origin of human trunk NC remains undefined and current in vitro differentiation strategies induce only a modest yield of trunk NC cells. Here we show that hPSC-derived axial progenitors, the posteriorly-located drivers of embryonic axis elongation, give rise to trunk NC cells and their derivatives. Moreover, we define the molecular signatures associated with the emergence of human NC cells of distinct axial identities in vitro. Collectively, our findings indicate that there are two routes toward a human post-cranial NC state: the birth of cardiac and vagal NC is facilitated by retinoic acid-induced posteriorisation of an anterior precursor whereas trunk NC arises within a pool of posterior axial progenitors., Competing Interests: TF, IG, MW, ES, OT, KN, DS, PH, DO, JH, KA, MG, JB, VW, SJ, MP, MG, PA, AT No competing interests declared, (© 2018, Frith et al.)
- Published
- 2018
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21. Characterizing the activity of abundant, diverse and active CRISPR-Cas systems in lactobacilli.
- Author
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Crawley AB, Henriksen ED, Stout E, Brandt K, and Barrangou R
- Subjects
- Bacteriophages genetics, Gene Expression Profiling, Genetic Variation, Genome, Bacterial, Plasmids, RNA, Guide, CRISPR-Cas Systems genetics, CRISPR-Cas Systems, Lactobacillus enzymology, Lactobacillus genetics, Recombination, Genetic
- Abstract
CRISPR-Cas systems provide immunity against phages and plasmids in bacteria and archaea. Despite the popularity of CRISPR-Cas9 based genome editing, few endogenous systems have been characterized to date. Here, we sampled 1,262 publically available lactobacilli genomes found them to be enriched with CRISPR-Cas adaptive immunity. While CRISPR-Cas is ubiquitous in some Lactobacillus species, CRISPR-Cas content varies at the strain level in most Lactobacillus species. We identified that Type II is the most abundant type across the genus, with II-A being the most dominant sub-type. We found that many Type II-A systems are actively transcribed, and encode spacers that efficiently provide resistance against plasmid uptake. Analysis of various CRISPR transcripts revealed that guide sequences are highly diverse in terms of crRNA and tracrRNA length and structure. Interference assays revealed highly diverse target PAM sequences. Lastly, we show that these systems can be readily repurposed for self-targeting by expressing an engineered single guide RNA. Our results reveal that Type II-A systems in lactobacilli are naturally active in their native host in terms of expression and efficiently targeting invasive and genomic DNA. Together, these systems increase the possible Cas9 targeting space and provide multiplexing potential in native hosts and heterologous genome editing purpose.
- Published
- 2018
- Full Text
- View/download PDF
22. Postinduction butorphanol administration alters oxygen consumption to improve blood gases in etorphine-immobilized white rhinoceros.
- Author
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Buss P, Miller M, Fuller A, Haw A, Stout E, Olea-Popelka F, and Meyer L
- Subjects
- Animals, Blood Gas Analysis veterinary, Immobilization adverse effects, Immobilization methods, Injections, Intramuscular veterinary, Male, Respiration drug effects, Butorphanol pharmacology, Etorphine pharmacology, Hypnotics and Sedatives pharmacology, Immobilization veterinary, Narcotic Antagonists pharmacology, Oxygen Consumption drug effects, Perissodactyla blood, Perissodactyla metabolism
- Abstract
Objective: To investigate the effects of postinduction butorphanol administration in etorphine-immobilized white rhinoceros on respiration and blood gases., Study Design: Randomized crossover study., Animals: A group of six sub-adult male white rhinoceros., Methods: Etorphine, or etorphine followed by butorphanol 12 minutes after recumbency, was administered intramuscularly [2.5 mg etorphine, 25 mg butorphanol (1000-1250 kg), or 3.0 mg etorphine, 30 mg butorphanol (1250-1500 kg)]. Sampling started at 10 minutes after initial recumbency, and was repeated at 5 minute intervals for 25 minutes. Arterial blood gases, limb muscle tremors, expired minute ventilation and respiratory frequency were measured at each sampling point. Calculated values included alveolar-arterial oxygen gradient [ [Formula: see text] ], expected respiratory minute volume (V˙e), tidal volume (Vt), oxygen consumption ( [Formula: see text] ) and carbon dioxide production ( [Formula: see text] )., Results: Etorphine administration resulted in an initial median (range) hypoxaemia [arterial partial pressure of oxygen 25.0 (23.0-28.0) mmHg], hypercapnia [arterial partial pressure of carbon dioxide 76.2 (67.2-81.2) mmHg], increased [Formula: see text] [41.7 (36.6-45.1) mmHg, [Formula: see text] [11.1 (10.0-12.0) L minute
-1 ] and muscle tremors. Butorphanol administration was followed by rapid, although moderate, improvements in arterial partial pressure of oxygen [48.5 (42.0-51.0) mmHg] and arterial partial pressure of carbon dioxide [62.8 (57.9-75.2) mmHg]. In rhinoceros administered butorphanol, [Formula: see text] [4.4 (3.6-5.1) L minute-1 ] and [Formula: see text] [4.2 (3.8-4.4) L minute-1 ] were lower than in those not administered butorphanol. Increased arterial oxygen tension was associated with lower oxygen consumption (p=0.002) which was positively associated with lower muscle tremor scores (p<0.0001)., Conclusions and Clinical Relevance: Hypoxaemia and hypercapnia in etorphine-immobilized rhinoceros resulted from an increased [ [Formula: see text] ] and increased [Formula: see text] and [Formula: see text] associated with muscle tremors. Rather than being associated with changes in V˙e, it appears that improved blood gases following butorphanol administration were a consequence of decreased [Formula: see text] associated with reduced muscle tremoring., (Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)- Published
- 2018
- Full Text
- View/download PDF
23. Can an Infusion of Federal Funds Result in Sustainable Projects? An Evaluation of Suicide Prevention Programs.
- Author
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Apsler R, Formica SW, Stout E, and Carr C
- Subjects
- Humans, Program Evaluation, Retrospective Studies, Financial Management organization & administration, Financing, Government, Suicide Prevention
- Abstract
Our study evaluated the sustainability of programs in early cohorts of the Garrett Lee Smith (GLS) Memorial Act suicide prevention initiative, a major source of federal funding for youth suicide prevention among states, tribes, and institutions of higher education. We sought to: (1) determine whether suicide prevention activities initiated with federal support continued after funding ended, and (2) identify factors associated with sustainment. Thirty-three sites between 1 and 4 years beyond the end of their GLS grant participated in a retrospective online survey assessing their level of suicide prevention activity 1 year before, during (during-GLS), and 1 year after funding (after-GLS). We found that, on average, sites experienced a 6% decrease in their overall level of activity from during- to after-GLS. Twenty-two (67% of responding sites) exhibited either an increase in activity level or no more than a 10% decline from during- to after-GLS periods. After-GLS scores for the 11 remaining sites declined between 11 and 30% from their during-GLS levels. We conducted semi-structured follow-up interviews with 13 sites that successfully continued their activities to explore factors associated with sustainability. Our findings indicate that program actions in the during-GLS period associated with sustainability included: maintaining a sustainability mindset, developing and nurturing partnerships and relationships, embedding services in parent organizations, pursuing new and diversified funding, and implementing cost-reduction efficiencies. Actions in the after-GLS period associated with sustainability included: obtaining funding from other sources, reconfiguring, and maintaining continuous leadership.
- Published
- 2017
- Full Text
- View/download PDF
24. CRISPR-Cas Technologies and Applications in Food Bacteria.
- Author
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Stout E, Klaenhammer T, and Barrangou R
- Subjects
- Bacterial Vaccines, Bacteriophages genetics, Food Industry, Gene Editing, Genes, Bacterial, Interspersed Repetitive Sequences, Probiotics, Bacteria genetics, Bacteria immunology, CRISPR-Cas Systems, Food Microbiology
- Abstract
Clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins form adaptive immune systems that occur in many bacteria and most archaea. In addition to protecting bacteria from phages and other invasive mobile genetic elements, CRISPR-Cas molecular machines can be repurposed as tool kits for applications relevant to the food industry. A primary concern of the food industry has long been the proper management of food-related bacteria, with a focus on both enhancing the outcomes of beneficial microorganisms such as starter cultures and probiotics and limiting the presence of detrimental organisms such as pathogens and spoilage microorganisms. This review introduces CRISPR-Cas as a novel set of technologies to manage food bacteria and offers insights into CRISPR-Cas biology. It primarily focuses on the applications of CRISPR-Cas systems and tools in starter cultures and probiotics, encompassing strain-typing, phage resistance, plasmid vaccination, genome editing, and antimicrobial activity.
- Published
- 2017
- Full Text
- View/download PDF
25. Cytotoxic effects on tumour cell lines of fatty acids from the marine sponge Scopalina ruetzleri.
- Author
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Biegelmeyer R, Schröder R, Rambo DF, Dresch RR, Stout EP, Carraro JL, Mothes B, Moreira JC, Molinski TF, da Frota Junior ML, and Henriques AT
- Subjects
- Animals, Antineoplastic Agents chemistry, Antioxidants chemistry, Antioxidants pharmacology, Cell Line, Tumor, Fatty Acids chemistry, Fatty Acids toxicity, Humans, Antineoplastic Agents pharmacology, Cell Survival drug effects, Fatty Acids pharmacology, Porifera chemistry
- Abstract
Objectives: Marine sponges are among the most promising sources of chemically diversified fatty acids (FAs). In addition, several studies have shown the effect of polyunsaturated FAs on cancer therapy. This research carried out a biological and chemical evaluation of the sponge Scopalina ruetzleri collected on the South Brazilian coastline., Methods: Bioassay-guided fractionation of S. ruetzleri was performed in human glioma (U87) and neuroblastoma (SH-SY5Y) cell lines, and the in-vitro effects on free radicals were evaluated., Key Findings: The ethyl acetate fraction of S. ruetzleri showed promising cytotoxic effects in cancer cell lines, with IC50 < 20 μg/ml. Fingerprint (1) H Nuclear Magnetic Resonance (NMR) analysis showed that this fraction is mainly constituted of FAs. Through FA methyl ester analysis, it was possible to identify 32 FAs. In addition, some minor unusual FAs for the marine biosphere were identified. The results of conjugated dienes method showed that FAs fraction, at concentrations above 50 μg/ml, has a pro-oxidant effect, indicating that lipid peroxidation may be partially responsible for the mechanism of cytotoxicity on cancer cells., Conclusion: This work also contributes to studies that focus on the application of FAs on cancer therapy as a new adjuvant to radio or chemotherapy, or as a chemotherapeutic agent., (© 2015 Royal Pharmaceutical Society.)
- Published
- 2015
- Full Text
- View/download PDF
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