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677 results on '"Kopelman, R."'

1. Spontaneous Charge aggregation and Polarization Model for Electric Discharges in Clouds

Author

Tsouchnika, M., Kanetidis, M., Argyrakis, P., and Kopelman, R.

Subjects
Physics - Computational Physics, Condensed Matter - Soft Condensed Matter
Abstract

In present models cloud based lightning forms as a consequence of the earth's gravitational and/or electromagnetic fields. Our simplified field-free model probes the random aggregation of a neutral ensemble consisting of a random distribution of equal numbers of equally charged positive and negative "frozen droplets", given a bivariate sticking probability. Over a wide range of parameters, one maximal cluster (called "cloud") is formed, with time-increasing mass, net charge and electric dipole moment, where all relations follow a simple argument, and the only parameter is the fractal dimension of the cloud: In this overall neutral system we find that the net charge of the cloud increases with the square root of the cloud's mass, while the electric dipole moment increases quasi-linearly and even superlinearly. Thus an internal electric field can be self-created by a random process, with a field-strength that increases with time and cloud size, using just a two-dimensional random walk. Potential implications of this toy model on "real life" clouds are discussed, i.e., the electric dipole moment based possibility of having intra-cloud lightning discharges, and the net electric charge based possibility of having extra-cloud lightning discharges, all in the absence of gravitational or other external fields or forces. Possible implications are discussed for both water and dust based clouds, atmospheric and extraterrestrial. Potential applications to biology are also discussed., Comment: 28 pages, 13 pages paper and 15 pages supplemental. 4 figures and 13 supp. figures

Published
2018

2. Combining Active Carbonic Anhydrase with Nanogels: Enzyme Protection and Zinc Sensing

Author

Si D, Nie G, Hurst TK, Fierke CA, and Kopelman R

Subjects
paam hydrogel, nanogel, nanoparticles, carbonic anhydrase, encapsulation, conjugation, zn2+., Medicine (General), R5-920
Abstract

Di Si,1 Guochao Nie,2– 4 Tamiika K Hurst,1 Carol A Fierke,1 Raoul Kopelman1 1Department of Chemistry, University of Michigan, Ann Arbor, MI, USA; 2School of Physics and Telecommunication Engineering, Yulin Normal University, Yulin, People’s Republic of China; 3China-Ukraine Joint Research Center for Nano Carbon Black, Yulin, People’s Republic of China; 4Guangxi Key Laboratory of Agricultural Resources Chemistry and Biotechnology, Yulin, People’s Republic of ChinaCorrespondence: Guochao NieSchool of Physics and Telecommunication Engineering, Yulin Normal University, Yulin, People’s Republic of ChinaEmail bccu518@ylu.edu.cnRaoul KopelmanDepartment of Chemistry, University of Michigan, 930 N University Avenue, Ann Arbor, MI, USAEmail kopelman@umich.eduBackground: Due to its excellent biocompatibility, the polyacrylamide (PAAm) hydrogel has shown great potential for the immobilization of enzymes used in biomedical applications. The major challenge involved is to preserve, during the immobilization process, both the biological activity and the structural integrity of the enzymes. Here we report, for the first time, a proof-of-concept study for embedding active carbonic anhydrase (CA) into polyacrylamide (PAAm) nanogels. By immobilizing CA in these nanogels, we hope to provide important advantages, such as matrix protection of the CA as well as its targeted delivery, and also for potentially using these nanogels as zinc nano-biosensors, both in-vitro and in-vivo.Methods and Results: Two methods are reported here for CA immobilization: encapsulation and surface conjugation. In the encapsulation method, the common process was improved, so as to best preserve the CA, by 1) using a novel biofriendly nonionic surfactant system (Span 80/Tween 80/Brij 30) and 2) using an Al2O3 adsorptive filtration purification procedure. In the surface conjugation method, blank PAAm nanogels were activated by N-hydroxysuccinimide and the CA was cross-linked to the nanogels. The amount of active CA immobilized in the nanoparticles was quantified for both methods. Per 1 g nanogels, the CA encapsulated nanogels contain 11.3 mg active CA, while the CA conjugated nanogels contain 22.5 mg active CA. Also, the CA conjugated nanoparticles successfully measured free Zn2+ levels in solution, with the Zn2+ dissociation constant determined to be 9 pM.Conclusion: This work demonstrates universal methods for immobilizing highly fragile bio-macromolecules inside nanoparticle carriers, while preserving their structural integrity and biological activity. The advantages and limitations are discussed, as well as the potential biomedical applications.Keywords: PAAm hydrogel, nanogels, nanoparticles, carbonic anhydrase, encapsulation, conjugation, Zn2+

Published
2021

4. Magnetic particle biosensors

Author

Li, Y. (Yunzi), Kinnunen, P. (Päivö), Hrin, A. (Alexander), Burns, M. A. (Mark A.), and Kopelman, R. (Raoul)

Abstract

With the recent technological advances in the synthesis and characterization of nano- and microparticles, there has been a growing interest in applying this technology to different areas, such as diagnosis of diseases and detection of pollutants. The use of magnetic particles as biosensors is favored due to the mobility of magnetic particles under magnetic fields and the low magnetic background observed in most biological samples. This chapter briefly discusses the basic ways to modify the surface of magnetic particles to enhance interaction with biological targets, and thoroughly reviews the different applications of magnetic particles as biosensors. The use of magnetic particles is divided into three categories by the functionality of the magnetic particles in these biosensors, namely magnetic particles as carriers for signal intensification, magnetic particles as labels to detect magnetic contents, and bio-sensing based on the dynamics of magnetic particles. The strategy and theory of different magnetic particle biosensors are elucidated in details and illustrated through examples.

Published
2021

10. Effect of Cinacalcet on Cardiovascular Disease in Patients Undergoing Dialysis

Author

Chertow GM, Block GA, Correa-Rotter R, Drüeke TB, Floege J, Goodman WG, Herzog CA, Kubo Y, London GM, Mahaffey KW, Mix TC, Moe SM, Trotman ML, Wheeler DC, Parfrey PS., Evolve Team, Chertow G, Parfrey P, Block G, Drüeke T, Goodman W, Herzog C, London G, Mahaffey K, Moe S, Wheeler D, Hennekens C, Baigent C, Brown W, O'Brien P, Anderson S, Hoel J, Szczech L, Patel U, Wampole J, Pun P, Felker M, Inrig J, Shah S, Hernandez A, Patel C, Brennan M, Albizem M, Capper E, Cauchi L, Cheng S, Dehmel B, Dhami K, Durham C, Francioni M, Gadd S, Goodman B, Guimaraes L, Grey N, Hamlin R, Harris C, Harris E, Heavey S, Heiges T, Heiser D, Jaeger P, James M, James P, Karimi S, Kewalramani R, Kraszewski A, Liang J, Maguire J, McCormick K, McFarlane K, Mix C, Modafferi D, Prathikanti R, Ryan C, Santiago N, Schumacher J, Seder C, Shahinfar S, Soares B, Stolman D, Tisher C, Trotman M, Tseng S, Ulias G, Unger P, Vyshenskaya A, Walsh L, White C, Wilde K, Santos J, Zarazaga C, Marin I, Garrote N, Cusumano A, Penalba N, Del Valle E, Juncos L, Saye J, Lef L, Altobelli V, Petraglia G, Rosa-Diez G, Douthat W, Lobo J, Gallart C, Lafalla A, Diez G, Linares B, Lopez N, Ramirez N, Gonzalez R, Valtuille R, Beresan H, Hermida O, Rudolf G, Marchetta N, Rano M, Ramirez M, Garcia N, Gillies A, Jones B, Pedagogos E, Walker R, Talaulikar G, Bannister K, Suranyi M, Kark A, Roger S, Kerr P, Disney A, Mount P, Fraenkel M, Mathew M, Fassett R, Jose M, Hawley C, Lonergan M, Mackie J, Ferrari P, Menahem S, Sabto J, Hutchison B, Langham R, Pollock C, Holzer H, Oberbauer R, Arias I, Graf H, Mayer G, Lhotta K, Neyer U, Klauser-Braun R, Hoerl W, Horn S, Kovarik J, Kramar R, Eigner M, Dhaene M, Billiouw J, De Meester J, Warling X, Cambier-Dwelschauwers P, Evenepoel P, Daelemans R, Dratwa M, Maes B, Stolear J, Dejagere T, Vanwalleghem J, Bouman K, Jadoul M, Peeters J, Vanholder R, Tielemans C, Donck J, Almeida F, de Oliveira J, Burdmann E, Garcia V, Thome F, Deboni L, Bregman R, Lugon J, Araújo S, Ferreira Filho S, Daher Ede F, Baptista M, Carvalho A, d'Avila D, Moyses Neto M, Yu L, Bastos M, Lacativa P, Jorgetti V, Romão Ede A, da Costa JC, Pecoits Filho R, Gordan P, Salgado N, Araújo M, Coelho S, Oliveira I, Moysés R, Vasconcellos L, Batista P, Gross J, Pedrosa A, Cournoyer S, LeBlanc M, Chow S, Karunakaran S, Wong G, Tobe S, Desmeules S, Zimmerman D, Murphy S, Montambault P, Donnelly S, MacRae J, Culleton B, Soroka S, Rabbat C, Jindal K, Vasilevsky M, Michaud M, Wijeyesinghe E, Zacharias J, Lok C, Muirhead N, Verrelli M, Da Roza G, Sapir D, Olgaard K, Daugaard H, Brandi L, Jensen P, Boulechfar H, Ang K, Simon P, Rieu P, Brunet P, Touchard G, Torres P, Combe C, Durrbach A, Ortiz J, Hannedouche T, Vela C, Lionet A, Ryckelynck P, Zaoui P, Choukroun G, Fessi H, Lang P, Stroumza P, Joly D, Mousson C, Laville M, Dellanna F, Erley C, Braun J, Rambausek M, Riegel W, Klingberg M, Schwertfeger E, Wizemann V, Eckardt K, Reichel H, Passauer J, Hübel E, Frischmuth N, Liebl R, Fiedler R, Schwenger V, Voßkühler A, Kunzendorf U, Renders L, Rattensberger D, Rump L, Ketteler M, Neumayer H, Zantvoort F, Stahl R, Ladanyi E, Braun B, Kulcsar I, Mezei I, Csiky B, Rikker C, Arkossy O, Berta K, Szegedi J, Major L, Ferenczi S, Fekete A, Szabo T, Zakar G, Wagner G, Erdelyine S, Borbas B, Eustace J, Reddan D, Capasso G, Locatelli F, Villa G, Cozzolino M, Brancaccio D, Messa P, Bolasco P, Ricciardi B, Malberti F, Moriero E, Cannella G, Ortalda V, Stefoni S, Frascà G, Cappelli G, Albertazzi A, Zoccali C, Farina M, Elli A, Avella F, Ondei P, Mingardi G, Errico R, Losito A, Di Giulio S, Pertosa G, Schena F, Grandaliano G, Gesualdo L, Auricchio M, Bochicchio-Ricardelli T, Correa-Rotter J, Verástegui F, Peña J, Wong A, Cruz-Valdez J, Zamora M, Solis M, Diaz M, Flores M, Sandoval E, van den Dorpel M, Brink H, Van Kuijk W, Vermeij C, Gregoor P, Hagen E, van der Sande F, Klinger M, Nowicki M, Muszytowski M, Bidas K, Bentkowski W, Wiecek A, Ksiazek A, Marczewski K, Ostrowski M, Switalski M, Sulowicz W, Matuszkiewicz-Rowinska J, Mysliwiec M, Durlik M, Rutkowski B, Macario F, Carvalho B, Frazao J, Machado D, Weigert A, Andrusev A, Khrustalev O, Zemtchenkov A, Gurevich K, Staroselsky K, Khadikova N, Rozhinskaya L, Timokhovskaya G, Strokov A, Balkarova O, Ermolenko V, Kolmakova E, Komandenko M, Timofeev M, Shilo V, Shostka G, Smirnov A, Anashkin V, Volgina G, Domashenko O, Gurevich A, Perlin D, García J, Ribes E, Piera E, Lucas M, Galicia M, Prados M, González M, Romero R, de Francisco ÁM, Montenegro J, Santiago C, García F, de La Ossa J, Arrieta J, Pons J, Martín-Malo A, Amigó J, Cases A, Sterner G, Jensen G, Wikström B, Jacobson S, Lund U, Weiss L, Ståhl A, von Albertini B, Burnier M, Meier P, Martin P, Uehlinger D, Dickenmann M, Yaqoob M, Zehnder D, Kalra P, Padmanabhan N, Roe S, Eadington D, Pritchard N, Hutchison A, Davies S, Wilkie M, Davies M, Pai P, Swift P, Kwan J, Goldsmith D, Tomson C, Stratton J, Dasgupta I, Sarkar S, Moustafa M, Gandhi K, Jamal A, Galindo-Ramos E, Tuazon J, Batlle D, Tucker K, Schiller-Moran B, Assefi A, Martinez C, Samuels L, Goldman J, Cangiano-Rivera J, Darwish R, Lee M, Topf J, Kapatkin K, Baer H, Kopelman R, Acharya M, Tharpe D, Bernardo M, Nader P, Guzman-Rivera J, Pergola P, Sekkarie M, Alas E, Zager P, Liss K, Navarro J, Roppolo M, Denu-Ciocca C, Kshirsagar A, El Khatib M, Kant K, Scott D, Murthyr B, Finkelstein F, Keightley G, McCrary R, Pitone J, Cavalieri T, Tsang A, Pellegrino B, Schmidt R, Ahmad S, Brown C, Friedman E, Mittman N, Fadem S, Shapiro W, Reddy M, Goldberger S, Woredekal Y, Agarwal A, Anger M, Haque M, Chidester P, Kohli R, Rubinstein S, Newman G, Gladish R, Ayodeji O, Soman S, Sprague S, Hunt N, Gehr T, Rizk D, Warnock D, Polack D, Pahl M, Fischer D, Dreyer P, James G, Husserl F, Rogers T, Raff A, Sedor J, Silver M, Smith M, Steinberg S, DelGiorno T, Jones E, Cunha P, Cheng J, Pogue V, Blumenthal S, Brown E, Charytan C, Buerkert J, Cook M, Felsenfeld A, Tareen N, Gupta A, Herman T, Diamond S, Hura C, Laski M, MacLaurin J, Plumb T, Brosnahan G, Kumar J, Henriquez M, Poole C, Osanloo E, Matalon A, Sholer C, Arfeen S, Azer M, Belledonne M, Gross M, Dunnigan E, McConnell K, Becker B, Rigolosi R, Spiegel D, Stegman M, Patak R, Streja D, Ranjit U, Youell T, Wooldridge T, Stafford C, Cottiero R, Weinberg M, Schonefeld M, Shahmir E, Hazzan A, Ashfaq A, Bhandari K, Cleveland W, Culpepper M, Golden J, Lai L, Lien Y, Lorica V, Robertson J, Malireddi K, Morse S, Thakur V, Israelit A, Raguram P, Alfred H, Weise W, Al-Saghir F, El Shahawy M, Rastogi A, Nissenson A, Kopyt N, Lynn R, Lea J, McClellan W, Teredesai P, Ong S, Tolkan S, Sugihara J, Minga T, Mehrotra R, Minasian R, Bhatia D, Specter R, Capelli J, Sidhu P, Dalal S, Dykes P, Khan M, Rahim F, Saklayen M, Thomas A, Michael B, Torres M, Al-Bander H, Murray B, Abukurah A, Gupta B, Nosrati S, Raja R, Zeig S, Braun M, Amatya A, Endsley J, Sharon Z, Dolson G, Dumler F, Ntoso K, Rosansky S, Kumar N, Gura V, Thompson N, Goldfarb D, Halligan R, Middleton J, Widerhorn A, Arbeit L, Arruda J, Crouch T, Friedman L, Khokhar S, Mittleman J, Light P, Taparia B, West C, Cotton J, Dhingra R, Kleinman L, Arif F, Lew S, Nammour T, Sterrett J, Williams M, Ramirez J, Rubin J, McCarthy J, Noble S, Chaffin M, Rekhi A., Chertow, Gm, Block, Ga, Correa-Rotter, R, Drüeke, Tb, Floege, J, Goodman, Wg, Herzog, Ca, Kubo, Y, London, Gm, Mahaffey, Kw, Mix, Tc, Moe, Sm, Trotman, Ml, Wheeler, Dc, Parfrey, Ps., Evolve, Team, Chertow, G, Parfrey, P, Block, G, Drüeke, T, Goodman, W, Herzog, C, London, G, Mahaffey, K, Moe, S, Wheeler, D, Hennekens, C, Baigent, C, Brown, W, O'Brien, P, Anderson, S, Hoel, J, Szczech, L, Patel, U, Wampole, J, Pun, P, Felker, M, Inrig, J, Shah, S, Hernandez, A, Patel, C, Brennan, M, Albizem, M, Capper, E, Cauchi, L, Cheng, S, Dehmel, B, Dhami, K, Durham, C, Francioni, M, Gadd, S, Goodman, B, Guimaraes, L, Grey, N, Hamlin, R, Harris, C, Harris, E, Heavey, S, Heiges, T, Heiser, D, Jaeger, P, James, M, James, P, Karimi, S, Kewalramani, R, Kraszewski, A, Liang, J, Maguire, J, Mccormick, K, Mcfarlane, K, Mix, C, Modafferi, D, Prathikanti, R, Ryan, C, Santiago, N, Schumacher, J, Seder, C, Shahinfar, S, Soares, B, Stolman, D, Tisher, C, Trotman, M, Tseng, S, Ulias, G, Unger, P, Vyshenskaya, A, Walsh, L, White, C, Wilde, K, Santos, J, Zarazaga, C, Marin, I, Garrote, N, Cusumano, A, Penalba, N, Del Valle, E, Juncos, L, Saye, J, Lef, L, Altobelli, V, Petraglia, G, Rosa-Diez, G, Douthat, W, Lobo, J, Gallart, C, Lafalla, A, Diez, G, Linares, B, Lopez, N, Ramirez, N, Gonzalez, R, Valtuille, R, Beresan, H, Hermida, O, Rudolf, G, Marchetta, N, Rano, M, Ramirez, M, Garcia, N, Gillies, A, Jones, B, Pedagogos, E, Walker, R, Talaulikar, G, Bannister, K, Suranyi, M, Kark, A, Roger, S, Kerr, P, Disney, A, Mount, P, Fraenkel, M, Mathew, M, Fassett, R, Jose, M, Hawley, C, Lonergan, M, Mackie, J, Ferrari, P, Menahem, S, Sabto, J, Hutchison, B, Langham, R, Pollock, C, Holzer, H, Oberbauer, R, Arias, I, Graf, H, Mayer, G, Lhotta, K, Neyer, U, Klauser-Braun, R, Hoerl, W, Horn, S, Kovarik, J, Kramar, R, Eigner, M, Dhaene, M, Billiouw, J, De Meester, J, Warling, X, Cambier-Dwelschauwers, P, Evenepoel, P, Daelemans, R, Dratwa, M, Maes, B, Stolear, J, Dejagere, T, Vanwalleghem, J, Bouman, K, Jadoul, M, Peeters, J, Vanholder, R, Tielemans, C, Donck, J, Almeida, F, de Oliveira, J, Burdmann, E, Garcia, V, Thome, F, Deboni, L, Bregman, R, Lugon, J, Araújo, S, Ferreira Filho, S, Daher Ede, F, Baptista, M, Carvalho, A, D'Avila, D, Moyses Neto, M, Yu, L, Bastos, M, Lacativa, P, Jorgetti, V, Romão Ede, A, da Costa, Jc, Pecoits Filho, R, Gordan, P, Salgado, N, Araújo, M, Coelho, S, Oliveira, I, Moysés, R, Vasconcellos, L, Batista, P, Gross, J, Pedrosa, A, Cournoyer, S, Leblanc, M, Chow, S, Karunakaran, S, Wong, G, Tobe, S, Desmeules, S, Zimmerman, D, Murphy, S, Montambault, P, Donnelly, S, Macrae, J, Culleton, B, Soroka, S, Rabbat, C, Jindal, K, Vasilevsky, M, Michaud, M, Wijeyesinghe, E, Zacharias, J, Lok, C, Muirhead, N, Verrelli, M, Da Roza, G, Sapir, D, Olgaard, K, Daugaard, H, Brandi, L, Jensen, P, Boulechfar, H, Ang, K, Simon, P, Rieu, P, Brunet, P, Touchard, G, Torres, P, Combe, C, Durrbach, A, Ortiz, J, Hannedouche, T, Vela, C, Lionet, A, Ryckelynck, P, Zaoui, P, Choukroun, G, Fessi, H, Lang, P, Stroumza, P, Joly, D, Mousson, C, Laville, M, Dellanna, F, Erley, C, Braun, J, Rambausek, M, Riegel, W, Klingberg, M, Schwertfeger, E, Wizemann, V, Eckardt, K, Reichel, H, Passauer, J, Hübel, E, Frischmuth, N, Liebl, R, Fiedler, R, Schwenger, V, Voßkühler, A, Kunzendorf, U, Renders, L, Rattensberger, D, Rump, L, Ketteler, M, Neumayer, H, Zantvoort, F, Stahl, R, Ladanyi, E, Braun, B, Kulcsar, I, Mezei, I, Csiky, B, Rikker, C, Arkossy, O, Berta, K, Szegedi, J, Major, L, Ferenczi, S, Fekete, A, Szabo, T, Zakar, G, Wagner, G, Erdelyine, S, Borbas, B, Eustace, J, Reddan, D, Capasso, G, Locatelli, F, Villa, G, Cozzolino, M, Brancaccio, D, Messa, P, Bolasco, P, Ricciardi, B, Malberti, F, Moriero, E, Cannella, G, Ortalda, V, Stefoni, S, Frascà, G, Cappelli, G, Albertazzi, A, Zoccali, C, Farina, M, Elli, A, Avella, F, Ondei, P, Mingardi, G, Errico, R, Losito, A, Di Giulio, S, Pertosa, G, Schena, F, Grandaliano, G, Gesualdo, L, Auricchio, M, Bochicchio-Ricardelli, T, Correa-Rotter, J, Verástegui, F, Peña, J, Wong, A, Cruz-Valdez, J, Zamora, M, Solis, M, Diaz, M, Flores, M, Sandoval, E, van den Dorpel, M, Brink, H, Van Kuijk, W, Vermeij, C, Gregoor, P, Hagen, E, van der Sande, F, Klinger, M, Nowicki, M, Muszytowski, M, Bidas, K, Bentkowski, W, Wiecek, A, Ksiazek, A, Marczewski, K, Ostrowski, M, Switalski, M, Sulowicz, W, Matuszkiewicz-Rowinska, J, Mysliwiec, M, Durlik, M, Rutkowski, B, Macario, F, Carvalho, B, Frazao, J, Machado, D, Weigert, A, Andrusev, A, Khrustalev, O, Zemtchenkov, A, Gurevich, K, Staroselsky, K, Khadikova, N, Rozhinskaya, L, Timokhovskaya, G, Strokov, A, Balkarova, O, Ermolenko, V, Kolmakova, E, Komandenko, M, Timofeev, M, Shilo, V, Shostka, G, Smirnov, A, Anashkin, V, Volgina, G, Domashenko, O, Gurevich, A, Perlin, D, García, J, Ribes, E, Piera, E, Lucas, M, Galicia, M, Prados, M, González, M, Romero, R, de Francisco, Ám, Montenegro, J, Santiago, C, García, F, de La Ossa, J, Arrieta, J, Pons, J, Martín-Malo, A, Amigó, J, Cases, A, Sterner, G, Jensen, G, Wikström, B, Jacobson, S, Lund, U, Weiss, L, Ståhl, A, von Albertini, B, Burnier, M, Meier, P, Martin, P, Uehlinger, D, Dickenmann, M, Yaqoob, M, Zehnder, D, Kalra, P, Padmanabhan, N, Roe, S, Eadington, D, Pritchard, N, Hutchison, A, Davies, S, Wilkie, M, Davies, M, Pai, P, Swift, P, Kwan, J, Goldsmith, D, Tomson, C, Stratton, J, Dasgupta, I, Sarkar, S, Moustafa, M, Gandhi, K, Jamal, A, Galindo-Ramos, E, Tuazon, J, Batlle, D, Tucker, K, Schiller-Moran, B, Assefi, A, Martinez, C, Samuels, L, Goldman, J, Cangiano-Rivera, J, Darwish, R, Lee, M, Topf, J, Kapatkin, K, Baer, H, Kopelman, R, Acharya, M, Tharpe, D, Bernardo, M, Nader, P, Guzman-Rivera, J, Pergola, P, Sekkarie, M, Alas, E, Zager, P, Liss, K, Navarro, J, Roppolo, M, Denu-Ciocca, C, Kshirsagar, A, El Khatib, M, Kant, K, Scott, D, Murthyr, B, Finkelstein, F, Keightley, G, Mccrary, R, Pitone, J, Cavalieri, T, Tsang, A, Pellegrino, B, Schmidt, R, Ahmad, S, Brown, C, Friedman, E, Mittman, N, Fadem, S, Shapiro, W, Reddy, M, Goldberger, S, Woredekal, Y, Agarwal, A, Anger, M, Haque, M, Chidester, P, Kohli, R, Rubinstein, S, Newman, G, Gladish, R, Ayodeji, O, Soman, S, Sprague, S, Hunt, N, Gehr, T, Rizk, D, Warnock, D, Polack, D, Pahl, M, Fischer, D, Dreyer, P, James, G, Husserl, F, Rogers, T, Raff, A, Sedor, J, Silver, M, Smith, M, Steinberg, S, Delgiorno, T, Jones, E, Cunha, P, Cheng, J, Pogue, V, Blumenthal, S, Brown, E, Charytan, C, Buerkert, J, Cook, M, Felsenfeld, A, Tareen, N, Gupta, A, Herman, T, Diamond, S, Hura, C, Laski, M, Maclaurin, J, Plumb, T, Brosnahan, G, Kumar, J, Henriquez, M, Poole, C, Osanloo, E, Matalon, A, Sholer, C, Arfeen, S, Azer, M, Belledonne, M, Gross, M, Dunnigan, E, Mcconnell, K, Becker, B, Rigolosi, R, Spiegel, D, Stegman, M, Patak, R, Streja, D, Ranjit, U, Youell, T, Wooldridge, T, Stafford, C, Cottiero, R, Weinberg, M, Schonefeld, M, Shahmir, E, Hazzan, A, Ashfaq, A, Bhandari, K, Cleveland, W, Culpepper, M, Golden, J, Lai, L, Lien, Y, Lorica, V, Robertson, J, Malireddi, K, Morse, S, Thakur, V, Israelit, A, Raguram, P, Alfred, H, Weise, W, Al-Saghir, F, El Shahawy, M, Rastogi, A, Nissenson, A, Kopyt, N, Lynn, R, Lea, J, Mcclellan, W, Teredesai, P, Ong, S, Tolkan, S, Sugihara, J, Minga, T, Mehrotra, R, Minasian, R, Bhatia, D, Specter, R, Capelli, J, Sidhu, P, Dalal, S, Dykes, P, Khan, M, Rahim, F, Saklayen, M, Thomas, A, Michael, B, Torres, M, Al-Bander, H, Murray, B, Abukurah, A, Gupta, B, Nosrati, S, Raja, R, Zeig, S, Braun, M, Amatya, A, Endsley, J, Sharon, Z, Dolson, G, Dumler, F, Ntoso, K, Rosansky, S, Kumar, N, Gura, V, Thompson, N, Goldfarb, D, Halligan, R, Middleton, J, Widerhorn, A, Arbeit, L, Arruda, J, Crouch, T, Friedman, L, Khokhar, S, Mittleman, J, Light, P, Taparia, B, West, C, Cotton, J, Dhingra, R, Kleinman, L, Arif, F, Lew, S, Nammour, T, Sterrett, J, Williams, M, Ramirez, J, Rubin, J, Mccarthy, J, Noble, S, Chaffin, M, and Rekhi, A.

Subjects
Adult, Male, Dialysis, Cinacalcet, Cardiovascular Disease, medicine.medical_specialty, Calcimimetic, medicine.medical_treatment, Naphthalenes, Coronary artery disease, Renal Dialysis, Internal medicine, Odds Ratio, medicine, Humans, Intensive care medicine, Aged, Etelcalcetide, Hyperparathyroidism, Hypocalcemia, business.industry, General Medicine, Middle Aged, medicine.disease, Intention to Treat Analysis, Cardiovascular Diseases, Parathyroid Hormone, Cinacalcet Hydrochloride, Kidney Failure, Chronic, Female, Hyperparathyroidism, Secondary, Secondary hyperparathyroidism, business, medicine.drug
Abstract

Disorders of mineral metabolism, including secondary hyperparathyroidism, are thought to contribute to extraskeletal (including vascular) calcification among patients with chronic kidney disease. It has been hypothesized that treatment with the calcimimetic agent cinacalcet might reduce the risk of death or nonfatal cardiovascular events in such patients.In this clinical trial, we randomly assigned 3883 patients with moderate-to-severe secondary hyperparathyroidism (median level of intact parathyroid hormone, 693 pg per milliliter [10th to 90th percentile, 363 to 1694]) who were undergoing hemodialysis to receive either cinacalcet or placebo. All patients were eligible to receive conventional therapy, including phosphate binders, vitamin D sterols, or both. The patients were followed for up to 64 months. The primary composite end point was the time until death, myocardial infarction, hospitalization for unstable angina, heart failure, or a peripheral vascular event. The primary analysis was performed on the basis of the intention-to-treat principle.The median duration of study-drug exposure was 21.2 months in the cinacalcet group, versus 17.5 months in the placebo group. The primary composite end point was reached in 938 of 1948 patients (48.2%) in the cinacalcet group and 952 of 1935 patients (49.2%) in the placebo group (relative hazard in the cinacalcet group vs. the placebo group, 0.93; 95% confidence interval, 0.85 to 1.02; P=0.11). Hypocalcemia and gastrointestinal adverse events were significantly more frequent in patients receiving cinacalcet.In an unadjusted intention-to-treat analysis, cinacalcet did not significantly reduce the risk of death or major cardiovascular events in patients with moderate-to-severe secondary hyperparathyroidism who were undergoing dialysis. (Funded by Amgen; EVOLVE ClinicalTrials.gov number, NCT00345839.).

Published
2012
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12. Cinacalcet, fibroblast growth factor-23, and cardiovascular disease in hemodialysis: The evaluation of cinacalcet HCl therapy to lower cardiovascular events (EVOLVE) trial

Author

Moe S. M., Chertow G. M., Parfrey P. S., Kubo Y., Block G. A., Correa-Rotter R., Drueke T. B., Herzog C. A., London G. M., Mahaffey K. W., Wheeler D. C., Stolina M., Dehmel B., Goodman W. G., Floege J., Santos J., Najun Zarazaga C., Marin I., Garrote N., Cusumano A., Penalba N., Del Valle E., Juncos L., Martinez Saye J., Lef L., Altobelli V., Petraglia G., Rosa Diez G., Douthat W., Lobo J., Gallart C., Lafalla A., Diez G., Linares B., Lopez N., Ramirez N., Gonzalez R., Valtuille R., Beresan H., Hermida O., Rudolf G., Marchetta N., Rano M., Ramirez M., Garcia N., Gillies A., Jones B., Pedagogos E., Walker R., Talaulikar G., Bannister K., Suranyi M., Kark A., Roger S., Kerr P., Disney A., Mount P., Fraenkel M., Mathew M., Fassett R., Jose M., Hawley C., Lonergan M., Mackie J., Ferrari P., Menahem S., Sabto J., Hutchison B., Langham R., Pollock C., Holzer H., Oberbauer R., Arias I., Graf H., Mayer G., Lhotta K., Neyer U., Klauser R., Hoerl W., Horn S., Kovarik J., Kramar R., Eigner M., Dhaene M., Billiouw J., De Meester J., Warling X., Cambier-Dwelschauwers P., Evenepoel P., Daelemans R., Dratwa M., Maes B., Stolear J., Dejagere T., Vanwalleghem J., Bouman K., Jadoul M., Peeters J., Vanholder R., Tielemans C., Donck J., Almeida F., Picollo De Oliveira J., Burdmann E., Garcia V., Saldanha Thome F., Deboni L., Bregman R., Lugon J., Araujo S., Ferreira Filho S., De Francesco Daher E., Sperto Baptista M., Carvalho A., D'Avila D., Moyses Neto M., Yu L., Bastos M., Sampaio Lacativa P., Jorgetti V., De Almeida Romao E., Cardeal Da Costa J., Pecoits Filho R., Gordan P., Salgado N., Teixeira Araujo M., Neiva Coelho S., Oliveira I., Moyses R., Vasconcellos L., Batista P., Luiz Gross J., Pedrosa A., Cournoyer S., LeBlanc M., Chow S., Karunakaran S., Wong G., Tobe S., Desmeules S., Zimmerman D., Murphy S., Montambault P., Donnelly S., MacRae J., Culleton B., Soroka S., Rabbat C., Jindal K., Vasilevsky M., Michaud M., Wijeyesinghe E., Zacharias J., Lok C., Muirhead N., Verrelli M., Da Roza G., Sapir D., Olgaard K., Daugaard H., Brandi L., Jensen P., Boulechfar H., Ang K., Simon P., Rieu P., Brunet P., Touchard G., Urena Torres P., Combe C., Durrbach A., Ortiz J., Hannedouche T., Vela C., Lionet A., Ryckelynck P., Zaoui P., Choukroun G., Fessi H., Lang P., Stroumza P., Joly D., Mousson C., Laville M., Dellanna F., Erley C., Braun J., Rambausek M., Riegel W., Klingberg M., Schwertfeger E., Wizemann V., Eckardt K., Reichel H., Passauer J., Hubel E., Frischmuth N., Liebl R., Fiedler R., Schwenger V., Vosskuhler A., Kunzendorf U., Renders L., Rattensberger D., Rump L., Ketteler M., Neumayer H., Zantvoort F., Stahl R., Ladanyi E., Kulcsar I., Mezei I., Csiky B., Rikker C., Arkossy O., Berta K., Szegedi J., Major L., Ferenczi S., Fekete A., Szabo T., Zakar G., Wagner G., Kazup Erdelyine S., Borbas B., Eustace J., Reddan D., Capasso G., Locatelli F., Villa G., Cozzolino M., Brancaccio D., Messa P., Bolasco P., Ricciardi B., Malberti F., Moriero E., Cannella G., Ortalda V., Stefoni S., Frasca G., Cappelli G., Albertazzi A., Zoccali C., Farina M., Elli A., Avella F., Ondei P., Mingardi G., Errico R., Losito A., Di Giulio S., Pertosa G., Schena F., Grandaliano G., Gesualdo L., Auricchio M., Bochicchio-Ricardelli T., Aranda Verastegui F., Pena J., Chew Wong A., Cruz-Valdez J., Torres Zamora M., Solis M., Sebastian Diaz M., Vital Flores M., Alvarez Sandoval E., Van Den Dorpel M., Brink H., Van Kuijk W., Vermeij C., Smak Gregoor P., Hagen E., Van Der Sande F., Klinger M., Nowicki M., Muszytowski M., Bidas K., Bentkowski W., Wiecek A., Ksiazek A., Marczewski K., Ostrowski M., Switalski M., Sulowicz W., Matuszkiewicz-Rowinska J., Mysliwiec M., Durlik M., Rutkowski B., Macario F., Carvalho B., Frazao J., Machado D., Weigert A., Andrusev A., Khrustalev O., Zemtchenkov A., Gurevich K., Staroselsky K., Khadikova N., Rozhinskaya L., Timokhovskaya G., Strokov A., Balkarova O., Ermolenko V., Kolmakova E., Komandenko M., Timofeev M., Shilo V., Shostka G., Smirnov A., Anashkin V., Volgina G., Domashenko O., Gurevich A., Perlin D., Martinez Garcia J., Andres Ribes E., Coll Piera E., Fernandez Lucas M., Galicia M., Prados M., Gonzalez M., Romero R., Martin de Francisco A., Montenegro J., Santiago C., Garcia F., Alcazar De La Ossa J., Arrieta J., Pons J., Martin-Malo A., Soler Amigo J., Cases A., Sterner G., Jensen G., Wikstrom B., Jacobson S., Lund U., Weiss L., Stahl A., Von Albertini B., Burnier M., Meier P., Martin P., Uehlinger D., Dickenmann M., Yaqoob M., Zehnder D., Kalra P., Padmanabhan N., Roe S., Eadington D., Pritchard N., Hutchison A., Davies S., Wilkie M., Davies M., Pai P., Swift P., Kwan J., Goldsmith D., Tomson C., Stratton J., Dasgupta I., Sarkar S., Moustafa M., Gandhi K., Jamal A., Galindo-Ramos E., Tuazon J., Batlle D., Tucker K., Schiller-Moran B., Assefi A., Martinez C., Samuels L., Goldman J., Cangiano-Rivera J., Darwish R., Lee M., Topf J., Kapatkin K., Baer H., Kopelman R., Acharya M., Tharpe D., Bernardo M., Nader P., Guzman-Rivera J., Pergola P., Sekkarie M., Alas E., Zager P., Liss K., Navarro J., Roppolo M., Denu-Ciocca C., Kshirsagar A., El Khatib M., Kant K., Scott D., Murthyr B., Finkelstein F., Keightley G., McCrary R., Pitone J., Cavalieri T., Tsang A., Pellegrino B., Schmidt R., Ahmad S., Brown C., Friedman E., Mittman N., Fadem S., Shapiro W., Reddy M., Goldberger S., Woredekal Y., Agarwal A., Anger M., Haque M., Chidester P., Kohli R., Rubinstein S., Newman G., Gladish R., Ayodeji O., Soman S., Sprague S., Hunt N., Gehr T., Rizk D., Warnock D., Polack D., Pahl M., Fischer D., Dreyer P., James G., Husserl F., Rogers T., Raff A., Sedor J., Silver M., Smith M., Steinberg S., DelGiorno T., Jones E., Cunha P. D., Cheng J., Pogue V., Blumenthal S., Brown E., Charytan C., Buerkert J., Cook M., Felsenfeld A., Tareen N., Gupta A., Herman T., Diamond S., Hura C., Laski M., MacLaurin J., Plumb T., Brosnahan G., Kumar J., Henriquez M., Poole C., Osanloo E., Matalon A., Sholer C., Arfeen S., Azer M., Belledonne M., Gross M., Dunnigan E., McConnell K., Becker B., Skinner F., Rigolosi R., Spiegel D., Stegman M., Patak R., Streja D., Ranjit U., Youell T., Wooldridge T., Stafford C., Cottiero R., Weinberg M., Schonefeld M., Shahmir E., Hazzan A., Ashfaq A., Bhandari K., Cleveland W., Culpepper M., Golden J., Lai L., Lien Y., Lorica V., Robertson J., Malireddi K., Morse S., Thakur V., Israelit A., Raguram P., Alfred H., Weise W., Al-Saghir F., El Shahawy M., Rastogi A., Nissenson A., Kopyt N., Lynn R., Lea J., McClellan W., Teredesai P., Ong S., Tolkan S., Sugihara J., Minga T., Mehrotra R., Minasian R., Bhatia D., Specter R., Capelli J., Sidhu P., Dalal S., Dykes P., Khan M., Rahim F., Saklayen M., Thomas A., Michael B., Torres M., Al-Bander H., Murray B., Abukurah A., Gupta B., Nosrati S., Raja R., Zeig S., Braun M., Amatya A., Endsley J., Sharon Z., Dolson G., Dumler F., Ntoso K., Rosansky S., Kumar N., Gura V., Thompson N., Goldfarb D., Halligan R., Middleton J., Widerhorn A., Arbeit L., Arruda J., Crouch T., Friedman L., Khokhar S., Mittleman J., Light P., Taparia B., West C., Cotton J., Dhingra R., Kleinman L., Arif F., Lew S., Nammour T., Sterrett J., Williams M., Ramirez J., Rubin J., McCarthy J., Noble S., Chaffin M., Rekhi A., Moe, S. M., Chertow, G. M., Parfrey, P. S., Kubo, Y., Block, G. A., Correa-Rotter, R., Drueke, T. B., Herzog, C. A., London, G. M., Mahaffey, K. W., Wheeler, D. C., Stolina, M., Dehmel, B., Goodman, W. G., Floege, J., Santos, J., Najun Zarazaga, C., Marin, I., Garrote, N., Cusumano, A., Penalba, N., Del Valle, E., Juncos, L., Martinez Saye, J., Lef, L., Altobelli, V., Petraglia, G., Rosa Diez, G., Douthat, W., Lobo, J., Gallart, C., Lafalla, A., Diez, G., Linares, B., Lopez, N., Ramirez, N., Gonzalez, R., Valtuille, R., Beresan, H., Hermida, O., Rudolf, G., Marchetta, N., Rano, M., Ramirez, M., Garcia, N., Gillies, A., Jones, B., Pedagogos, E., Walker, R., Talaulikar, G., Bannister, K., Suranyi, M., Kark, A., Roger, S., Kerr, P., Disney, A., Mount, P., Fraenkel, M., Mathew, M., Fassett, R., Jose, M., Hawley, C., Lonergan, M., Mackie, J., Ferrari, P., Menahem, S., Sabto, J., Hutchison, B., Langham, R., Pollock, C., Holzer, H., Oberbauer, R., Arias, I., Graf, H., Mayer, G., Lhotta, K., Neyer, U., Klauser, R., Hoerl, W., Horn, S., Kovarik, J., Kramar, R., Eigner, M., Dhaene, M., Billiouw, J., De Meester, J., Warling, X., Cambier-Dwelschauwers, P., Evenepoel, P., Daelemans, R., Dratwa, M., Maes, B., Stolear, J., Dejagere, T., Vanwalleghem, J., Bouman, K., Jadoul, M., Peeters, J., Vanholder, R., Tielemans, C., Donck, J., Almeida, F., Picollo De Oliveira, J., Burdmann, E., Garcia, V., Saldanha Thome, F., Deboni, L., Bregman, R., Lugon, J., Araujo, S., Ferreira Filho, S., De Francesco Daher, E., Sperto Baptista, M., Carvalho, A., D'Avila, D., Moyses Neto, M., Yu, L., Bastos, M., Sampaio Lacativa, P., Jorgetti, V., De Almeida Romao, E., Cardeal Da Costa, J., Pecoits Filho, R., Gordan, P., Salgado, N., Teixeira Araujo, M., Neiva Coelho, S., Oliveira, I., Moyses, R., Vasconcellos, L., Batista, P., Luiz Gross, J., Pedrosa, A., Cournoyer, S., Leblanc, M., Chow, S., Karunakaran, S., Wong, G., Tobe, S., Desmeules, S., Zimmerman, D., Murphy, S., Montambault, P., Donnelly, S., Macrae, J., Culleton, B., Soroka, S., Rabbat, C., Jindal, K., Vasilevsky, M., Michaud, M., Wijeyesinghe, E., Zacharias, J., Lok, C., Muirhead, N., Verrelli, M., Da Roza, G., Sapir, D., Olgaard, K., Daugaard, H., Brandi, L., Jensen, P., Boulechfar, H., Ang, K., Simon, P., Rieu, P., Brunet, P., Touchard, G., Urena Torres, P., Combe, C., Durrbach, A., Ortiz, J., Hannedouche, T., Vela, C., Lionet, A., Ryckelynck, P., Zaoui, P., Choukroun, G., Fessi, H., Lang, P., Stroumza, P., Joly, D., Mousson, C., Laville, M., Dellanna, F., Erley, C., Braun, J., Rambausek, M., Riegel, W., Klingberg, M., Schwertfeger, E., Wizemann, V., Eckardt, K., Reichel, H., Passauer, J., Hubel, E., Frischmuth, N., Liebl, R., Fiedler, R., Schwenger, V., Vosskuhler, A., Kunzendorf, U., Renders, L., Rattensberger, D., Rump, L., Ketteler, M., Neumayer, H., Zantvoort, F., Stahl, R., Ladanyi, E., Kulcsar, I., Mezei, I., Csiky, B., Rikker, C., Arkossy, O., Berta, K., Szegedi, J., Major, L., Ferenczi, S., Fekete, A., Szabo, T., Zakar, G., Wagner, G., Kazup Erdelyine, S., Borbas, B., Eustace, J., Reddan, D., Capasso, G., Locatelli, F., Villa, G., Cozzolino, M., Brancaccio, D., Messa, P., Bolasco, P., Ricciardi, B., Malberti, F., Moriero, E., Cannella, G., Ortalda, V., Stefoni, S., Frasca, G., Cappelli, G., Albertazzi, A., Zoccali, C., Farina, M., Elli, A., Avella, F., Ondei, P., Mingardi, G., Errico, R., Losito, A., Di Giulio, S., Pertosa, G., Schena, F., Grandaliano, G., Gesualdo, L., Auricchio, M., Bochicchio-Ricardelli, T., Aranda Verastegui, F., Pena, J., Chew Wong, A., Cruz-Valdez, J., Torres Zamora, M., Solis, M., Sebastian Diaz, M., Vital Flores, M., Alvarez Sandoval, E., Van Den Dorpel, M., Brink, H., Van Kuijk, W., Vermeij, C., Smak Gregoor, P., Hagen, E., Van Der Sande, F., Klinger, M., Nowicki, M., Muszytowski, M., Bidas, K., Bentkowski, W., Wiecek, A., Ksiazek, A., Marczewski, K., Ostrowski, M., Switalski, M., Sulowicz, W., Matuszkiewicz-Rowinska, J., Mysliwiec, M., Durlik, M., Rutkowski, B., Macario, F., Carvalho, B., Frazao, J., Machado, D., Weigert, A., Andrusev, A., Khrustalev, O., Zemtchenkov, A., Gurevich, K., Staroselsky, K., Khadikova, N., Rozhinskaya, L., Timokhovskaya, G., Strokov, A., Balkarova, O., Ermolenko, V., Kolmakova, E., Komandenko, M., Timofeev, M., Shilo, V., Shostka, G., Smirnov, A., Anashkin, V., Volgina, G., Domashenko, O., Gurevich, A., Perlin, D., Martinez Garcia, J., Andres Ribes, E., Coll Piera, E., Fernandez Lucas, M., Galicia, M., Prados, M., Gonzalez, M., Romero, R., Martin de Francisco, A., Montenegro, J., Santiago, C., Garcia, F., Alcazar De La Ossa, J., Arrieta, J., Pons, J., Martin-Malo, A., Soler Amigo, J., Cases, A., Sterner, G., Jensen, G., Wikstrom, B., Jacobson, S., Lund, U., Weiss, L., Stahl, A., Von Albertini, B., Burnier, M., Meier, P., Martin, P., Uehlinger, D., Dickenmann, M., Yaqoob, M., Zehnder, D., Kalra, P., Padmanabhan, N., Roe, S., Eadington, D., Pritchard, N., Hutchison, A., Davies, S., Wilkie, M., Davies, M., Pai, P., Swift, P., Kwan, J., Goldsmith, D., Tomson, C., Stratton, J., Dasgupta, I., Sarkar, S., Moustafa, M., Gandhi, K., Jamal, A., Galindo-Ramos, E., Tuazon, J., Batlle, D., Tucker, K., Schiller-Moran, B., Assefi, A., Martinez, C., Samuels, L., Goldman, J., Cangiano-Rivera, J., Darwish, R., Lee, M., Topf, J., Kapatkin, K., Baer, H., Kopelman, R., Acharya, M., Tharpe, D., Bernardo, M., Nader, P., Guzman-Rivera, J., Pergola, P., Sekkarie, M., Alas, E., Zager, P., Liss, K., Navarro, J., Roppolo, M., Denu-Ciocca, C., Kshirsagar, A., El Khatib, M., Kant, K., Scott, D., Murthyr, B., Finkelstein, F., Keightley, G., Mccrary, R., Pitone, J., Cavalieri, T., Tsang, A., Pellegrino, B., Schmidt, R., Ahmad, S., Brown, C., Friedman, E., Mittman, N., Fadem, S., Shapiro, W., Reddy, M., Goldberger, S., Woredekal, Y., Agarwal, A., Anger, M., Haque, M., Chidester, P., Kohli, R., Rubinstein, S., Newman, G., Gladish, R., Ayodeji, O., Soman, S., Sprague, S., Hunt, N., Gehr, T., Rizk, D., Warnock, D., Polack, D., Pahl, M., Fischer, D., Dreyer, P., James, G., Husserl, F., Rogers, T., Raff, A., Sedor, J., Silver, M., Smith, M., Steinberg, S., Delgiorno, T., Jones, E., Cunha, P. D., Cheng, J., Pogue, V., Blumenthal, S., Brown, E., Charytan, C., Buerkert, J., Cook, M., Felsenfeld, A., Tareen, N., Gupta, A., Herman, T., Diamond, S., Hura, C., Laski, M., Maclaurin, J., Plumb, T., Brosnahan, G., Kumar, J., Henriquez, M., Poole, C., Osanloo, E., Matalon, A., Sholer, C., Arfeen, S., Azer, M., Belledonne, M., Gross, M., Dunnigan, E., Mcconnell, K., Becker, B., Skinner, F., Rigolosi, R., Spiegel, D., Stegman, M., Patak, R., Streja, D., Ranjit, U., Youell, T., Wooldridge, T., Stafford, C., Cottiero, R., Weinberg, M., Schonefeld, M., Shahmir, E., Hazzan, A., Ashfaq, A., Bhandari, K., Cleveland, W., Culpepper, M., Golden, J., Lai, L., Lien, Y., Lorica, V., Robertson, J., Malireddi, K., Morse, S., Thakur, V., Israelit, A., Raguram, P., Alfred, H., Weise, W., Al-Saghir, F., El Shahawy, M., Rastogi, A., Nissenson, A., Kopyt, N., Lynn, R., Lea, J., Mcclellan, W., Teredesai, P., Ong, S., Tolkan, S., Sugihara, J., Minga, T., Mehrotra, R., Minasian, R., Bhatia, D., Specter, R., Capelli, J., Sidhu, P., Dalal, S., Dykes, P., Khan, M., Rahim, F., Saklayen, M., Thomas, A., Michael, B., Torres, M., Al-Bander, H., Murray, B., Abukurah, A., Gupta, B., Nosrati, S., Raja, R., Zeig, S., Braun, M., Amatya, A., Endsley, J., Sharon, Z., Dolson, G., Dumler, F., Ntoso, K., Rosansky, S., Kumar, N., Gura, V., Thompson, N., Goldfarb, D., Halligan, R., Middleton, J., Widerhorn, A., Arbeit, L., Arruda, J., Crouch, T., Friedman, L., Khokhar, S., Mittleman, J., Light, P., Taparia, B., West, C., Cotton, J., Dhingra, R., Kleinman, L., Arif, F., Lew, S., Nammour, T., Sterrett, J., Williams, M., Ramirez, J., Rubin, J., Mccarthy, J., Noble, S., Chaffin, M., Rekhi, A., and Clinical sciences

Subjects
Adult, Male, Fibroblast growth factor 23, medicine.medical_specialty, Cinacalcet, Calcimimetic, medicine.medical_treatment, Naphthalenes, Hyperthyroidism, Gastroenterology, ventricular remodeling, Renal Dialysis, Cinacalcet Hydrochloride, Physiology (medical), Internal medicine, medicine, Humans, renal insufficiency, chronic, Aged, Etelcalcetide, calcium, business.industry, Research Support, Non-U.S. Gov't, death, sudden, cardiac, Middle Aged, arrhythmias, cardiac, Cardiovascular Diseases, Female, Fibroblast Growth Factors, Cardiology and Cardiovascular Medicine, medicine.disease, Fibroblast Growth Factor-23, Endocrinology, Randomized Controlled Trial, Secondary hyperparathyroidism, Hemodialysis, business, medicine.drug, Kidney disease
Abstract

Background— Patients with kidney disease have disordered bone and mineral metabolism, including elevated serum concentrations of fibroblast growth factor-23 (FGF23). These elevated concentrations are associated with cardiovascular and all-cause mortality. The objective was to determine the effects of the calcimimetic cinacalcet (versus placebo) on reducing serum FGF23 and whether changes in FGF23 are associated with death and cardiovascular events. Methods and Results— This was a secondary analysis of a randomized clinical trial comparing cinacalcet to placebo in addition to conventional therapy (phosphate binders/vitamin D) in patients receiving hemodialysis with secondary hyperparathyroidism (intact parathyroid hormone ≥300 pg/mL). The primary study end point was time to death or a first nonfatal cardiovascular event (myocardial infarction, hospitalization for angina, heart failure, or a peripheral vascular event). This analysis included 2985 patients (77% of randomized) with serum samples at baseline and 2602 patients (67%) with samples at both baseline and week 20. The results demonstrated that a significantly larger proportion of patients randomized to cinacalcet had ≥30% (68% versus 28%) reductions in FGF23. Among patients randomized to cinacalcet, a ≥30% reduction in FGF23 between baseline and week 20 was associated with a nominally significant reduction in the primary composite end point (relative hazard, 0.82; 95% confidence interval, 0.69–0.98), cardiovascular mortality (relative hazard, 0.66; 95% confidence interval, 0.50–0.87), sudden cardiac death (relative hazard, 0.57; 95% confidence interval, 0.37–0.86), and heart failure (relative hazard, 0.69; 95% confidence interval, 0.48–0.99). Conclusions— Treatment with cinacalcet significantly lowers serum FGF23. Treatment-induced reductions in serum FGF23 are associated with lower rates of cardiovascular death and major cardiovascular events. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00345839.

Published
2015

46. Reaction kinetics on clusters and islands.

Author

Newhouse, J. S. and Kopelman, R.

Subjects
*MONTE Carlo method, *NUCLEAR physics, *CHEMICAL reactions, *DYNAMICS, *CLUSTER theory (Nuclear physics)
Abstract

States that Monte Carlo simulations yield anomalous high reaction orders for elementary binary reactions on finite percolation clusters and monodisperse island ensembles. Exciton fusion reactions on naphthalene percolation clusters in isotopic mixed crystals; Nonclassical behavior.

Published
1986
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