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2. Inflammation and changes in cytokine levels in neurological feline infectious peritonitis

Author

Foley, JE, Rand, C, and Leutenegger, C

Subjects
Infectious Diseases, Neurosciences, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Good Health and Well Being, Animals, Brain, Case-Control Studies, Cats, Chemokine CCL4, Chemokine CCL5, Coronavirus, Feline, Cytokines, DNA Primers, Encephalitis, Feline Infectious Peritonitis, Inflammation, Interleukin-6, Macrophage Inflammatory Proteins, Reverse Transcriptase Polymerase Chain Reaction, Veterinary Sciences
Abstract

Feline infectious peritonitis (FIP) is a progressive, fatal, predominantly Arthus-type immune-mediated disease that is triggered when cats are infected with a mutant enteric coronavirus. The disease presents variably with multiple organ failure, seizures, generalized effusion, or shock. Neurological FIP is clinically and pathologically more homogeneous than systemic 'wet' or 'dry' FIP; thus, comparison of cytokine profiles from cats with neurological FIP, wet FIP, and non-FIP neurological disease may provide insight into some baseline characteristics relating to the immunopathogenesis of neurological FIP. This study characterizes inflammation and changes in cytokines in the brain tissue of FIP-affected cats. Cellular infiltrates in cats with FIP included lymphocytes, plasma cells, neutrophils, macrophages, and eosinophils. IL-1 beta, IL-6, IL-12, IL-18, TNF-alpha, macrophage inhibitory protein (MIP)-1 alpha, and RANTES showed no upregulation in the brains of control cats, moderate upregulation in neurological FIP cats, and very high upregulation in generalized FIP cats. Transcription of IFN-gamma appeared upregulated in cats with systemic FIP and slightly downregulated in neurological FIP. In most cytokines tested, variance was extremely high in generalized FIP and much less in neurological FIP. Principal components analysis was performed in order to find the least number of 'components' that would summarize the cytokine profiles in cats with neurological FIP. A large component of the variance (91.7%) was accounted for by levels of IL-6, MIP-1 alpha, and RANTES. These findings provide new insight into the immunopathogenesis of FIP and suggest targets for immune therapy of this disease.

Published
2003

6. DIII-D research towards establishing the scientific basis for future fusion reactors

Author

Abadie, L, Abrams, T, Ahn, J, Akiyama, T, Aleynikov, P, Allcock, J, Allen, E, Allen, S, Anderson, J, Ashourvan, A, Austin, M, Bak, J, Barada, K, Barbour, N, Bardoczi, L, Barr, J, Barton, J, Bass, E, Battaglia, D, Baylor, L, Beckers, J, Belli, E, Berkery, J, Bertelli, N, Bialek, J, Boedo, J, Boivin, R, Bonoli, P, Bortolon, A, Boyer, M, Brambila, R, Bray, B, Brennan, D, Briesemeister, A, Bringuier, S, Brookman, M, Brower, D, Brown, B, Brown, W, Buchenauer, D, Burke, M, Burrell, K, Butt, J, Buttery, R, Bykov, I, Candy, J, Canik, J, Cao, N, Carbajal Gomez, L, Carlson, L, Carlstrom, T, Carter, T, Cary, W, Casali, L, Cengher, M, Chan, V, Chen, B, Chen, J, Chen, M, Chen, R, Chen, X, Choi, W, Chrobak, C, Chrystal, C, Churchill, R, Cianciosa, M, Clauser, C, Clement, M, Coburn, J, Collins, C, Cooper, A, Covele, B, Crippen, J, Crocker, N, Crowley, B, Dal Molin, A, Davis, E, Degrassie, J, del-Castillo-Negrete, C, Delgado-Aparicio, L, Diallo, A, Diem, S, Ding, R, Ding, S, Ding, W, Doane, J, Donovan, D, Drake, J, Du, D, Du, H, Du, X, Duarte, V, Duran, J, Eidietis, N, Elder, D, Eldon, D, Elwasif, W, Ely, T, Eng, K, Engelhorn, K, Ennis, D, Erickson, K, Ernst, D, Evans, T, Fenstermacher, M, Ferraro, N, Ferron, J, Finkenthal, D, Fisher, P, Fishler, B, Flanagan, S, Fooks, J, Frassinetti, L, Frerichs, H, Fu, Y, Fulop, T, Gao, Q, Garcia, F, Garofalo, A, Gattuso, A, Giacomelli, L, Giraldez, E, Giroud, C, Glass, F, Gohil, P, Gong, X, Gorelov, Y, Granetz, R, Green, D, Greenfield, C, Grierson, B, Groebner, R, Grosnickle, W, Groth, M, Grunloh, H, Guo, H, Guo, W, Guterl, J, Hager, R, Hahn, S, Halpern, F, Han, H, Hansink, M, Hanson, J, Harris, J, Haskey, S, Hatch, D, Heidbrink, W, Herfindal, J, Hill, D, Hill, M, Hinson, E, Holcomb, C, Holland, C, Holland, L, Hollmann, E, Holm, A, Hong, R, Hoppe, M, Houshmandyar, S, Howard, J, Howard, N, Hu, Q, Hu, W, Huang, H, Huang, J, Huang, Y, Hughes, G, Hughes, J, Humphreys, D, Hyatt, A, Ida, K, Igochine, V, In, Y, Inoue, S, Isayama, A, Isler, R, Izzo, V, Jackson, M, Jarvinen, A, Jeon, Y, Ji, H, Jian, X, Jimenez, R, Johnson, C, Joseph, I, Kaczala, D, Kaplan, D, Kates-Harbeck, J, Kellman, A, Kellman, D, Kessel, C, Khumthong, K, Kim, C, Kim, H, Kim, J, Kim, K, Kim, S, Kimura, W, King, J, Kirk, A, Kleijwegt, K, Knolker, M, Kohn, A, Kolemen, E, Kostuk, M, Kramer, G, Kress, P, Kriete, D, La Haye, R, Laggner, F, Lan, H, Lanctot, M, Lantsov, R, Lao, L, Lasnier, C, Lau, C, Law, K, Lawrence, D, Le, J, Lee, R, Lehnen, M, Leon, R, Leonard, A, Lesher, M, Leuer, J, Li, G, Li, K, Liao, K, Lin, Z, Liu, C, Liu, F, Liu, Y, Liu, Z, Loch, S, Logan, N, Lohr, J, Lore, J, Luce, T, Luhmann, N, Lunsford, R, Luo, C, Luo, Z, Lupin-Jimenez, L, Lvovskiy, A, Lyons, B, Ma, X, Maingi, R, Makowski, M, Mantica, P, Manuel, M, Margo, M, Marinoni, A, Marmar, E, Martin, W, Masline, R, Matsunaga, G, Mauzey, D, Mauzey, P, Mcclenaghan, J, Mckee, G, Mclean, A, Mclean, H, Meier, E, Meitner, S, Menard, J, Meneghini, O, Merlo, G, Meyer, W, Miller, D, Miller, W, Moeller, C, Montes, K, Morales, M, Mordijck, S, Moser, A, Moyer, R, Muller, S, Munaretto, S, Murakami, M, Murphy, C, Muscatello, C, Myers, C, Nagy, A, Navratil, G, Nazikian, R, Neff, A, Neiser, T, Nelson, A, Nguyen, P, Nguyen, R, Nichols, J, Nocente, M, Nygren, R, O'Neill, R, Odstrcil, T, Ohdachi, S, Okabayashi, M, Olofsson, E, Ono, M, Orlov, D, Osborne, T, Pablant, N, Pace, D, Paguio, R, Pajares Martinez, A, Pan, C, Pankin, A, Park, J, Park, Y, Parker, C, Parker, S, Parks, P, Pawley, C, Paz-Soldan, C, Peebles, W, Penaflor, B, Petrie, T, Petty, C, Peysson, Y, Pigarov, A, Piglowski, D, Pinsker, R, Piovesan, P, Piper, N, Pitts, R, Pizzo, J, Podesta, M, Poli, F, Ponce, D, Porkolab, M, Porter, G, Prater, R, Qian, J, Ra, O, Rafiq, T, Raman, R, Rand, C, Randall, G, Rauch, J, Rea, C, Reinke, M, Ren, J, Ren, Q, Ren, Y, Rhodes, T, Rice, J, Rognlien, T, Rost, J, Rowan, W, Rudakov, D, Salmi, A, Sammuli, B, Samuell, C, Sandorfi, A, Sang, C, Sauter, O, Schissel, D, Schmitz, L, Schmitz, O, Schuster, E, Scoville, J, Seltzman, A, Sfiligoi, I, Shafer, M, Shen, H, Shi, T, Shiraki, D, Si, H, Smith, D, Smith, S, Snipes, J, Snyder, P, Solano, E, Solomon, W, Sontag, A, Soukhanovskii, V, Spong, D, Stacey, W, Staebler, G, Stagner, L, Stahl, B, Stangeby, P, Stoltzfus-Dueck, T, Stotler, D, Strait, E, Su, D, Sugiyama, L, Sulyman, A, Sun, Y, Sung, C, Suttrop, W, Suzuki, Y, Svyatkovskiy, A, Sweeney, R, Taimourzadeh, S, Takechi, M, Tala, T, Tan, H, Tang, S, Tang, X, Taussig, D, Taylor, G, Taylor, N, Taylor, T, Teklu, A, Thomas, D, Thomas, M, Thome, K, Thorman, A, Tinguely, R, Tobias, B, Tooker, J, Torreblanca, H, Torrezan De Sousa, A, Trevisan, G, Truong, D, Turco, F, Turnbull, A, Unterberg, E, Vaezi, P, Vail, P, Van Zeeland, M, Velasco Enriquez, M, Venkatesh, M, Victor, B, Volpe, F, Wade, M, Walker, M, Wall, J, Wallace, G, Waltz, R, Wang, G, Wang, H, Wang, Y, Wang, Z, Wang, F, Ward, S, Watkins, J, Watkins, M, Wehner, W, Weiland, M, Weisberg, D, Welander, A, White, A, White, R, Whyte, D, Wijkamp, T, Wilcox, R, Wilks, T, Wilson, H, Wingen, A, Wolfe, E, Wu, M, Wu, W, Wukitch, S, Xia, T, Xiang, N, Xiao, B, Xie, R, Xu, G, Xu, H, Xu, X, Yan, Z, Yang, Q, Yang, X, Yoshida, M, Yu, G, Yu, J, Yu, M, Zamperini, S, Zeng, L, Zhao, B, Zhao, D, Zhao, H, Zhao, Y, Zhu, Y, Zywicki, B, L. Abadie, T. W. Abrams, J. Ahn, T. Akiyama, P. Aleynikov, J. Allcock, E. O. Allen, S. Allen, J. P. Anderson, A. Ashourvan, M. E. Austin, J. Bak, K. K. Barada, N. Barbour, L. Bardoczi, J. Barr, J. L. Barton, E. M. Bass, D. Battaglia, L. R. Baylor, J. Beckers, E. A. Belli, J. W. Berkery, N. Bertelli, J. M. Bialek, J. A. Boedo, R. L. Boivin, P. T. Bonoli, A. Bortolon, M. D. Boyer, R. E. Brambila, B. Bray, D. P. Brennan, A. R. Briesemeister, S. A. Bringuier, M. W. Brookman, D. L. Brower, B. R. Brown, W. D. Brown, D. Buchenauer, M. G. Burke, K. H. Burrell, J. Butt, R. J. Buttery, I. Bykov, J. M. Candy, J. M. Canik, N. M. Cao, L. Carbajal Gomez, L. C. Carlson, T. N. Carlstrom, T. A. Carter, W. Cary, L. Casali, M. Cengher, V. S. Chan, B. Chen, J. Chen, M. Chen, R. Chen, Xi Chen, W. Choi, C. Chrobak, C. Chrystal, R. M. Churchill, M. Cianciosa, C. F. Clauser, M. Clement, J. Coburn, C. S. Collins, A. W. Cooper, B. M. Covele, J. W. Crippen, N. A. Crocker, B. J. Crowley, A. Dal Molin, E. M. Davis, J. S. deGrassie, C. A. del-Castillo-Negrete, L. F. Delgado-Aparicio, A. Diallo, S. J. Diem, R. Ding, S. Ding, W. Ding, J. L. Doane, D. C. Donovan, J. Drake, D. Du, H. Du, X. Du, V. Duarte, J. D. Duran, N. W. Eidietis, D. Elder, D. Eldon, W. Elwasif, T. E. Ely, K. M. Eng, K. Engelhorn, D. Ennis, K. Erickson, D. R. Ernst, T. E. Evans, M. E. Fenstermacher, N. M. Ferraro, J. R. Ferron, D. F. Finkenthal, P. A. Fisher, B. Fishler, S. M. Flanagan, J. A. Fooks, L. Frassinetti, H. G. Frerichs, Y. Fu, T. Fulop, Q. Gao, F. Garcia, A. M. Garofalo, A. Gattuso, L. Giacomelli, E. M. Giraldez, C. Giroud, F. Glass, P. Gohil, X. Gong, Y. A. Gorelov, R. S. Granetz, D. L. Green, C. M. Greenfield, B. A. Grierson, R. J. Groebner, W. H. Grosnickle, M. Groth, H. J. Grunloh, H. Y. Guo, W. Guo, J. Guterl, R. C. Hager, S. Hahn, F. D. Halpern, H. Han, M. J. Hansink, J. M. Hanson, J. Harris, S. R. Haskey, D. R. Hatch, W. W. Heidbrink, J. Herfindal, D. N. Hill, M. D. Hill, E. T. Hinson, C. T. Holcomb, C. G. Holland, L. D. Holland, E. M. Hollmann, A. M. Holm, R. Hong, M. Hoppe, S. Houshmandyar, J. Howard, N. T. Howard, Q. Hu, W. Hu, H. Huang, J. Huang, Y. Huang, G. A. Hughes, J. Hughes, D. A. Humphreys, A. W. Hyatt, K. Ida, V. Igochine, Y. In, S. Inoue, A. Isayama, R. C. Isler, V. A. Izzo, M. R. Jackson, A. E. Jarvinen, Y. Jeon, H. Ji, X. Jian, R. Jimenez, C. A. Johnson, I. Joseph, D. N. Kaczala, D. H. Kaplan, J. Kates-Harbeck, A. G. Kellman, D. H. Kellman, C. E. Kessel, K. Khumthong, C. C. Kim, H. Kim, J. Kim, K. Kim, S. H. Kim, W. Kimura, J. R. King, A. Kirk, K. Kleijwegt, M. Knolker, A. Kohn, E. Kolemen, M. Kostuk, G. J. Kramer, P. Kress, D. M. Kriete, R. J. La Haye, F. M. Laggner, H. Lan, M. J. Lanctot, R. Lantsov, L. L. Lao, C. J. Lasnier, C. Lau, K. Law, D. Lawrence, J. Le, R. L. Lee, M. Lehnen, R. Leon, A. W. Leonard, M. Lesher, J. A. Leuer, G. Li, K. Li, K. T. Liao, Z. Lin, C. Liu, F. Liu, Y. Liu, Z. Liu, S. Loch, N. C. Logan, J. M. Lohr, J. Lore, T. C. Luce, N. C. Luhmann, R. Lunsford, C. Luo, Z. Luo, L. Lupin-Jimenez, A. Lvovskiy, B. C. Lyons, X. Ma, R. Maingi, M. A. Makowski, P. Mantica, M. Manuel, M. W. Margo, A. Marinoni, E. Marmar, W. C. Martin, R. L. Masline, G. K. Matsunaga, D. M. Mauzey, P. S. Mauzey, J. T. Mcclenaghan, G. R. Mckee, A. G. Mclean, H. S. Mclean, E. Meier, S. J. Meitner, J. E. Menard, O. Meneghini, G. Merlo, W. H. Meyer, D. C. Miller, W. J. Miller, C. P. Moeller, K. J. Montes, M. A. Morales, S. Mordijck, A. Moser, R. A. Moyer, S. A. Muller, S. Munaretto, M. Murakami, C. J. Murphy, C. M. Muscatello, C. E. Myers, A. Nagy, G. A. Navratil, R. M. Nazikian, A. L. Neff, T. F. Neiser, A. Nelson, P. Nguyen, R. Nguyen, J. H. Nichols, M. Nocente, R. E. Nygren, R. C. O'Neill, T. Odstrcil, S. Ohdachi, M. Okabayashi, E. Olofsson, M. Ono, D. M. Orlov, T. H. Osborne, N. A. Pablant, D. C. Pace, R. R. Paguio, A. Pajares Martinez, C. Pan, A. Pankin, J. M. Park, J. Park, Y. Park, C. T. Parker, S. E. Parker, P. B. Parks, C. J. Pawley, C. A. Paz-Soldan, W. A. Peebles, B. G. Penaflor, T. W. Petrie, C. C. Petty, Y. Peysson, A. Y. Pigarov, D. A. Piglowski, R. I. Pinsker, P. Piovesan, N. Piper, R. A. Pitts, J. D. Pizzo, M. L. Podesta, F. M. Poli, D. Ponce, M. Porkolab, G. D. Porter, R. Prater, J. Qian, O. Ra, T. Rafiq, R. Raman, C. Rand, G. C. Randall, J. M. Rauch, C. Rea, M. L. Reinke, J. Ren, Q. Ren, Y. Ren, T. L. Rhodes, J. Rice, T. D. Rognlien, J. C. Rost, W. L. Rowan, D. L. Rudakov, A. Salmi, B. S. Sammuli, C. M. Samuell, A. M. Sandorfi, C. Sang, O. J. Sauter, D. P. Schissel, L. Schmitz, O. Schmitz, E. J. Schuster, J. T. Scoville, A. Seltzman, I. Sfiligoi, M. Shafer, H. Shen, T. Shi, D. Shiraki, H. Si, D. R. Smith, S. P. Smith, J. A. Snipes, P. B. Snyder, E. R. Solano, W. M. Solomon, A. C. Sontag, V. A. Soukhanovskii, D. A. Spong, W. M. Stacey, G. M. Staebler, L. Stagner, B. Stahl, P. C. Stangeby, T. J. Stoltzfus-Dueck, D. P. Stotler, E. J. Strait, D. Su, L. E. Sugiyama, A. A. Sulyman, Y. Sun, C. Sung, W. A. Suttrop, Y. Suzuki, A. Svyatkovskiy, R. M. Sweeney, S. Taimourzadeh, M. Takechi, T. Tala, H. Tan, S. Tang, X. Tang, D. Taussig, G. Taylor, N. Z. Taylor, T. S. Taylor, A. Teklu, D. M. Thomas, M. B. Thomas, K. E. Thome, A. R. Thorman, R. A. Tinguely, B. J. Tobias, J. F. Tooker, H. Torreblanca, A. Torrezan De Sousa, G. L. Trevisan, D. Truong, F. Turco, A. D. Turnbull, E. A. Unterberg, P. Vaezi, P. J. Vail, M. A. Van Zeeland, M. Velasco Enriquez, M. C. Venkatesh, B. S. Victor, F. Volpe, M. R. Wade, M. L. Walker, J. R. Wall, G. M. Wallace, R. E. Waltz, G. Wang, H. Wang, Y. Wang, Z. Wang, F. Wang, S. H. Ward, J. G. Watkins, M. Watkins, W. P. Wehner, M. Weiland, D. B. Weisberg, A. S. Welander, A. E. White, R. B. White, D. Whyte, T. A. Wijkamp, R. Wilcox, T. Wilks, H. R. Wilson, A. Wingen, E. Wolfe, M. Wu, W. Wu, S. J. Wukitch, T. Xia, N. Xiang, B. Xiao, R. Xie, G. Xu, H. Xu, X. Xu, Z. Yan, Q. Yang, X. Yang, M. Yoshida, G. Yu, J. H. Yu, M. Yu, S. A. Zamperini, L. Zeng, B. Zhao, D. Zhao, H. Zhao, Y. Zhao, Y. Zhu, B. Zywicki, Abadie, L, Abrams, T, Ahn, J, Akiyama, T, Aleynikov, P, Allcock, J, Allen, E, Allen, S, Anderson, J, Ashourvan, A, Austin, M, Bak, J, Barada, K, Barbour, N, Bardoczi, L, Barr, J, Barton, J, Bass, E, Battaglia, D, Baylor, L, Beckers, J, Belli, E, Berkery, J, Bertelli, N, Bialek, J, Boedo, J, Boivin, R, Bonoli, P, Bortolon, A, Boyer, M, Brambila, R, Bray, B, Brennan, D, Briesemeister, A, Bringuier, S, Brookman, M, Brower, D, Brown, B, Brown, W, Buchenauer, D, Burke, M, Burrell, K, Butt, J, Buttery, R, Bykov, I, Candy, J, Canik, J, Cao, N, Carbajal Gomez, L, Carlson, L, Carlstrom, T, Carter, T, Cary, W, Casali, L, Cengher, M, Chan, V, Chen, B, Chen, J, Chen, M, Chen, R, Chen, X, Choi, W, Chrobak, C, Chrystal, C, Churchill, R, Cianciosa, M, Clauser, C, Clement, M, Coburn, J, Collins, C, Cooper, A, Covele, B, Crippen, J, Crocker, N, Crowley, B, Dal Molin, A, Davis, E, Degrassie, J, del-Castillo-Negrete, C, Delgado-Aparicio, L, Diallo, A, Diem, S, Ding, R, Ding, S, Ding, W, Doane, J, Donovan, D, Drake, J, Du, D, Du, H, Du, X, Duarte, V, Duran, J, Eidietis, N, Elder, D, Eldon, D, Elwasif, W, Ely, T, Eng, K, Engelhorn, K, Ennis, D, Erickson, K, Ernst, D, Evans, T, Fenstermacher, M, Ferraro, N, Ferron, J, Finkenthal, D, Fisher, P, Fishler, B, Flanagan, S, Fooks, J, Frassinetti, L, Frerichs, H, Fu, Y, Fulop, T, Gao, Q, Garcia, F, Garofalo, A, Gattuso, A, Giacomelli, L, Giraldez, E, Giroud, C, Glass, F, Gohil, P, Gong, X, Gorelov, Y, Granetz, R, Green, D, Greenfield, C, Grierson, B, Groebner, R, Grosnickle, W, Groth, M, Grunloh, H, Guo, H, Guo, W, Guterl, J, Hager, R, Hahn, S, Halpern, F, Han, H, Hansink, M, Hanson, J, Harris, J, Haskey, S, Hatch, D, Heidbrink, W, Herfindal, J, Hill, D, Hill, M, Hinson, E, Holcomb, C, Holland, C, Holland, L, Hollmann, E, Holm, A, Hong, R, Hoppe, M, Houshmandyar, S, Howard, J, Howard, N, Hu, Q, Hu, W, Huang, H, Huang, J, Huang, Y, Hughes, G, Hughes, J, Humphreys, D, Hyatt, A, Ida, K, Igochine, V, In, Y, Inoue, S, Isayama, A, Isler, R, Izzo, V, Jackson, M, Jarvinen, A, Jeon, Y, Ji, H, Jian, X, Jimenez, R, Johnson, C, Joseph, I, Kaczala, D, Kaplan, D, Kates-Harbeck, J, Kellman, A, Kellman, D, Kessel, C, Khumthong, K, Kim, C, Kim, H, Kim, J, Kim, K, Kim, S, Kimura, W, King, J, Kirk, A, Kleijwegt, K, Knolker, M, Kohn, A, Kolemen, E, Kostuk, M, Kramer, G, Kress, P, Kriete, D, La Haye, R, Laggner, F, Lan, H, Lanctot, M, Lantsov, R, Lao, L, Lasnier, C, Lau, C, Law, K, Lawrence, D, Le, J, Lee, R, Lehnen, M, Leon, R, Leonard, A, Lesher, M, Leuer, J, Li, G, Li, K, Liao, K, Lin, Z, Liu, C, Liu, F, Liu, Y, Liu, Z, Loch, S, Logan, N, Lohr, J, Lore, J, Luce, T, Luhmann, N, Lunsford, R, Luo, C, Luo, Z, Lupin-Jimenez, L, Lvovskiy, A, Lyons, B, Ma, X, Maingi, R, Makowski, M, Mantica, P, Manuel, M, Margo, M, Marinoni, A, Marmar, E, Martin, W, Masline, R, Matsunaga, G, Mauzey, D, Mauzey, P, Mcclenaghan, J, Mckee, G, Mclean, A, Mclean, H, Meier, E, Meitner, S, Menard, J, Meneghini, O, Merlo, G, Meyer, W, Miller, D, Miller, W, Moeller, C, Montes, K, Morales, M, Mordijck, S, Moser, A, Moyer, R, Muller, S, Munaretto, S, Murakami, M, Murphy, C, Muscatello, C, Myers, C, Nagy, A, Navratil, G, Nazikian, R, Neff, A, Neiser, T, Nelson, A, Nguyen, P, Nguyen, R, Nichols, J, Nocente, M, Nygren, R, O'Neill, R, Odstrcil, T, Ohdachi, S, Okabayashi, M, Olofsson, E, Ono, M, Orlov, D, Osborne, T, Pablant, N, Pace, D, Paguio, R, Pajares Martinez, A, Pan, C, Pankin, A, Park, J, Park, Y, Parker, C, Parker, S, Parks, P, Pawley, C, Paz-Soldan, C, Peebles, W, Penaflor, B, Petrie, T, Petty, C, Peysson, Y, Pigarov, A, Piglowski, D, Pinsker, R, Piovesan, P, Piper, N, Pitts, R, Pizzo, J, Podesta, M, Poli, F, Ponce, D, Porkolab, M, Porter, G, Prater, R, Qian, J, Ra, O, Rafiq, T, Raman, R, Rand, C, Randall, G, Rauch, J, Rea, C, Reinke, M, Ren, J, Ren, Q, Ren, Y, Rhodes, T, Rice, J, Rognlien, T, Rost, J, Rowan, W, Rudakov, D, Salmi, A, Sammuli, B, Samuell, C, Sandorfi, A, Sang, C, Sauter, O, Schissel, D, Schmitz, L, Schmitz, O, Schuster, E, Scoville, J, Seltzman, A, Sfiligoi, I, Shafer, M, Shen, H, Shi, T, Shiraki, D, Si, H, Smith, D, Smith, S, Snipes, J, Snyder, P, Solano, E, Solomon, W, Sontag, A, Soukhanovskii, V, Spong, D, Stacey, W, Staebler, G, Stagner, L, Stahl, B, Stangeby, P, Stoltzfus-Dueck, T, Stotler, D, Strait, E, Su, D, Sugiyama, L, Sulyman, A, Sun, Y, Sung, C, Suttrop, W, Suzuki, Y, Svyatkovskiy, A, Sweeney, R, Taimourzadeh, S, Takechi, M, Tala, T, Tan, H, Tang, S, Tang, X, Taussig, D, Taylor, G, Taylor, N, Taylor, T, Teklu, A, Thomas, D, Thomas, M, Thome, K, Thorman, A, Tinguely, R, Tobias, B, Tooker, J, Torreblanca, H, Torrezan De Sousa, A, Trevisan, G, Truong, D, Turco, F, Turnbull, A, Unterberg, E, Vaezi, P, Vail, P, Van Zeeland, M, Velasco Enriquez, M, Venkatesh, M, Victor, B, Volpe, F, Wade, M, Walker, M, Wall, J, Wallace, G, Waltz, R, Wang, G, Wang, H, Wang, Y, Wang, Z, Wang, F, Ward, S, Watkins, J, Watkins, M, Wehner, W, Weiland, M, Weisberg, D, Welander, A, White, A, White, R, Whyte, D, Wijkamp, T, Wilcox, R, Wilks, T, Wilson, H, Wingen, A, Wolfe, E, Wu, M, Wu, W, Wukitch, S, Xia, T, Xiang, N, Xiao, B, Xie, R, Xu, G, Xu, H, Xu, X, Yan, Z, Yang, Q, Yang, X, Yoshida, M, Yu, G, Yu, J, Yu, M, Zamperini, S, Zeng, L, Zhao, B, Zhao, D, Zhao, H, Zhao, Y, Zhu, Y, Zywicki, B, L. Abadie, T. W. Abrams, J. Ahn, T. Akiyama, P. Aleynikov, J. Allcock, E. O. Allen, S. Allen, J. P. Anderson, A. Ashourvan, M. E. Austin, J. Bak, K. K. Barada, N. Barbour, L. Bardoczi, J. Barr, J. L. Barton, E. M. Bass, D. Battaglia, L. R. Baylor, J. Beckers, E. A. Belli, J. W. Berkery, N. Bertelli, J. M. Bialek, J. A. Boedo, R. L. Boivin, P. T. Bonoli, A. Bortolon, M. D. Boyer, R. E. Brambila, B. Bray, D. P. Brennan, A. R. Briesemeister, S. A. Bringuier, M. W. Brookman, D. L. Brower, B. R. Brown, W. D. Brown, D. Buchenauer, M. G. Burke, K. H. Burrell, J. Butt, R. J. Buttery, I. Bykov, J. M. Candy, J. M. Canik, N. M. Cao, L. Carbajal Gomez, L. C. Carlson, T. N. Carlstrom, T. A. Carter, W. Cary, L. Casali, M. Cengher, V. S. Chan, B. Chen, J. Chen, M. Chen, R. Chen, Xi Chen, W. Choi, C. Chrobak, C. Chrystal, R. M. Churchill, M. Cianciosa, C. F. Clauser, M. Clement, J. Coburn, C. S. Collins, A. W. Cooper, B. M. Covele, J. W. Crippen, N. A. Crocker, B. J. Crowley, A. Dal Molin, E. M. Davis, J. S. deGrassie, C. A. del-Castillo-Negrete, L. F. Delgado-Aparicio, A. Diallo, S. J. Diem, R. Ding, S. Ding, W. Ding, J. L. Doane, D. C. Donovan, J. Drake, D. Du, H. Du, X. Du, V. Duarte, J. D. Duran, N. W. Eidietis, D. Elder, D. Eldon, W. Elwasif, T. E. Ely, K. M. Eng, K. Engelhorn, D. Ennis, K. Erickson, D. R. Ernst, T. E. Evans, M. E. Fenstermacher, N. M. Ferraro, J. R. Ferron, D. F. Finkenthal, P. A. Fisher, B. Fishler, S. M. Flanagan, J. A. Fooks, L. Frassinetti, H. G. Frerichs, Y. Fu, T. Fulop, Q. Gao, F. Garcia, A. M. Garofalo, A. Gattuso, L. Giacomelli, E. M. Giraldez, C. Giroud, F. Glass, P. Gohil, X. Gong, Y. A. Gorelov, R. S. Granetz, D. L. Green, C. M. Greenfield, B. A. Grierson, R. J. Groebner, W. H. Grosnickle, M. Groth, H. J. Grunloh, H. Y. Guo, W. Guo, J. Guterl, R. C. Hager, S. Hahn, F. D. Halpern, H. Han, M. J. Hansink, J. M. Hanson, J. Harris, S. R. Haskey, D. R. Hatch, W. W. Heidbrink, J. Herfindal, D. N. Hill, M. D. Hill, E. T. Hinson, C. T. Holcomb, C. G. Holland, L. D. Holland, E. M. Hollmann, A. M. Holm, R. Hong, M. Hoppe, S. Houshmandyar, J. Howard, N. T. Howard, Q. Hu, W. Hu, H. Huang, J. Huang, Y. Huang, G. A. Hughes, J. Hughes, D. A. Humphreys, A. W. Hyatt, K. Ida, V. Igochine, Y. In, S. Inoue, A. Isayama, R. C. Isler, V. A. Izzo, M. R. Jackson, A. E. Jarvinen, Y. Jeon, H. Ji, X. Jian, R. Jimenez, C. A. Johnson, I. Joseph, D. N. Kaczala, D. H. Kaplan, J. Kates-Harbeck, A. G. Kellman, D. H. Kellman, C. E. Kessel, K. Khumthong, C. C. Kim, H. Kim, J. Kim, K. Kim, S. H. Kim, W. Kimura, J. R. King, A. Kirk, K. Kleijwegt, M. Knolker, A. Kohn, E. Kolemen, M. Kostuk, G. J. Kramer, P. Kress, D. M. Kriete, R. J. La Haye, F. M. Laggner, H. Lan, M. J. Lanctot, R. Lantsov, L. L. Lao, C. J. Lasnier, C. Lau, K. Law, D. Lawrence, J. Le, R. L. Lee, M. Lehnen, R. Leon, A. W. Leonard, M. Lesher, J. A. Leuer, G. Li, K. Li, K. T. Liao, Z. Lin, C. Liu, F. Liu, Y. Liu, Z. Liu, S. Loch, N. C. Logan, J. M. Lohr, J. Lore, T. C. Luce, N. C. Luhmann, R. Lunsford, C. Luo, Z. Luo, L. Lupin-Jimenez, A. Lvovskiy, B. C. Lyons, X. Ma, R. Maingi, M. A. Makowski, P. Mantica, M. Manuel, M. W. Margo, A. Marinoni, E. Marmar, W. C. Martin, R. L. Masline, G. K. Matsunaga, D. M. Mauzey, P. S. Mauzey, J. T. Mcclenaghan, G. R. Mckee, A. G. Mclean, H. S. Mclean, E. Meier, S. J. Meitner, J. E. Menard, O. Meneghini, G. Merlo, W. H. Meyer, D. C. Miller, W. J. Miller, C. P. Moeller, K. J. Montes, M. A. Morales, S. Mordijck, A. Moser, R. A. Moyer, S. A. Muller, S. Munaretto, M. Murakami, C. J. Murphy, C. M. Muscatello, C. E. Myers, A. Nagy, G. A. Navratil, R. M. Nazikian, A. L. Neff, T. F. Neiser, A. Nelson, P. Nguyen, R. Nguyen, J. H. Nichols, M. Nocente, R. E. Nygren, R. C. O'Neill, T. Odstrcil, S. Ohdachi, M. Okabayashi, E. Olofsson, M. Ono, D. M. Orlov, T. H. Osborne, N. A. Pablant, D. C. Pace, R. R. Paguio, A. Pajares Martinez, C. Pan, A. Pankin, J. M. Park, J. Park, Y. Park, C. T. Parker, S. E. Parker, P. B. Parks, C. J. Pawley, C. A. Paz-Soldan, W. A. Peebles, B. G. Penaflor, T. W. Petrie, C. C. Petty, Y. Peysson, A. Y. Pigarov, D. A. Piglowski, R. I. Pinsker, P. Piovesan, N. Piper, R. A. Pitts, J. D. Pizzo, M. L. Podesta, F. M. Poli, D. Ponce, M. Porkolab, G. D. Porter, R. Prater, J. Qian, O. Ra, T. Rafiq, R. Raman, C. Rand, G. C. Randall, J. M. Rauch, C. Rea, M. L. Reinke, J. Ren, Q. Ren, Y. Ren, T. L. Rhodes, J. Rice, T. D. Rognlien, J. C. Rost, W. L. Rowan, D. L. Rudakov, A. Salmi, B. S. Sammuli, C. M. Samuell, A. M. Sandorfi, C. Sang, O. J. Sauter, D. P. Schissel, L. Schmitz, O. Schmitz, E. J. Schuster, J. T. Scoville, A. Seltzman, I. Sfiligoi, M. Shafer, H. Shen, T. Shi, D. Shiraki, H. Si, D. R. Smith, S. P. Smith, J. A. Snipes, P. B. Snyder, E. R. Solano, W. M. Solomon, A. C. Sontag, V. A. Soukhanovskii, D. A. Spong, W. M. Stacey, G. M. Staebler, L. Stagner, B. Stahl, P. C. Stangeby, T. J. Stoltzfus-Dueck, D. P. Stotler, E. J. Strait, D. Su, L. E. Sugiyama, A. A. Sulyman, Y. Sun, C. Sung, W. A. Suttrop, Y. Suzuki, A. Svyatkovskiy, R. M. Sweeney, S. Taimourzadeh, M. Takechi, T. Tala, H. Tan, S. Tang, X. Tang, D. Taussig, G. Taylor, N. Z. Taylor, T. S. Taylor, A. Teklu, D. M. Thomas, M. B. Thomas, K. E. Thome, A. R. Thorman, R. A. Tinguely, B. J. Tobias, J. F. Tooker, H. Torreblanca, A. Torrezan De Sousa, G. L. Trevisan, D. Truong, F. Turco, A. D. Turnbull, E. A. Unterberg, P. Vaezi, P. J. Vail, M. A. Van Zeeland, M. Velasco Enriquez, M. C. Venkatesh, B. S. Victor, F. Volpe, M. R. Wade, M. L. Walker, J. R. Wall, G. M. Wallace, R. E. Waltz, G. Wang, H. Wang, Y. Wang, Z. Wang, F. Wang, S. H. Ward, J. G. Watkins, M. Watkins, W. P. Wehner, M. Weiland, D. B. Weisberg, A. S. Welander, A. E. White, R. B. White, D. Whyte, T. A. Wijkamp, R. Wilcox, T. Wilks, H. R. Wilson, A. Wingen, E. Wolfe, M. Wu, W. Wu, S. J. Wukitch, T. Xia, N. Xiang, B. Xiao, R. Xie, G. Xu, H. Xu, X. Xu, Z. Yan, Q. Yang, X. Yang, M. Yoshida, G. Yu, J. H. Yu, M. Yu, S. A. Zamperini, L. Zeng, B. Zhao, D. Zhao, H. Zhao, Y. Zhao, Y. Zhu, and B. Zywicki

Abstract

DIII-D research is addressing critical challenges in preparation for ITER and the next generation of fusion devices through focusing on plasma physics fundamentals that underpin key fusion goals, understanding the interaction of disparate core and boundary plasma physics, and developing integrated scenarios for achieving high performance fusion regimes. Fundamental investigations into fusion energy science find that anomalous dissipation of runaway electrons (RE) that arise following a disruption is likely due to interactions with RE-driven kinetic instabilities, some of which have been directly observed, opening a new avenue for RE energy dissipation using naturally excited waves. Dimensionless parameter scaling of intrinsic rotation and gyrokinetic simulations give a predicted ITER rotation profile with significant turbulence stabilization. Coherence imaging spectroscopy confirms near sonic flow throughout the divertor towards the target, which may account for the convection-dominated parallel heat flux. Core-boundary integration studies show that the small angle slot divertor achieves detachment at lower density and extends plasma cooling across the divertor target plate, which is essential for controlling heat flux and erosion. The Super H-mode regime has been extended to high plasma current (2.0 MA) and density to achieve very high pedestal pressures (∼30 kPa) and stored energy (3.2 MJ) with H 98y2 ≈ 1.6-2.4. In scenario work, the ITER baseline Q = 10 scenario with zero injected torque is found to have a fusion gain metric independent of current between q 95 = 2.8-3.7, and a lower limit of pedestal rotation for RMP ELM suppression has been found. In the wide pedestal QH-mode regime that exhibits improved performance and no ELMs, the start-up counter torque has been eliminated so that the entire discharge uses ≈0 injected torque and the operating space is more ITER-relevant. Finally, the high- (3.8) hybrid scenario has been extended to the high-density levels ne

Published
2019

7. Inhaler technique mastery and maintenance in healthcare professionals trained on different devices

Author

Bosnic-Anticevich, S., Callan, C., Chrystyn, H., Lavorini, F., Nikolaou, V., Kritikos, V., Dekhuijzen, P.N.R., Roche, N., Bjermer, L., Rand, C., Zwar, N., Price, D.B., Bosnic-Anticevich, S., Callan, C., Chrystyn, H., Lavorini, F., Nikolaou, V., Kritikos, V., Dekhuijzen, P.N.R., Roche, N., Bjermer, L., Rand, C., Zwar, N., and Price, D.B.

Abstract

Item does not contain fulltext, OBJECTIVE: Healthcare professionals (HCPs) are required to assess and train patients in the correct use of inhalers but are often unable to demonstrate correct technique themselves. We sought to assess the level of training required for HCPs to master and maintain device mastery when using two different dry powder inhalers (DPIs). METHODS: We conducted a randomized, un-blinded, crossover study in undergraduate HCPs who undertook a six-step training procedure (intuitive use, patient information leaflet, instructional video, individual tuition from expert, then two repeats of individual tuition) for the use of Turbuhaler(R) (an established device) and Spiromax(R) (a newer device, reportedly easier to use). Device mastery (absence of errors) was evaluated by expert assessors at each training step. Maintenance of mastery was assessed 4 +/- 1 week (visit 2) and 8 +/- 2 weeks (visit 3) after initial training (visit 1). RESULTS: Of 516 eligible participants, 113 (22%) demonstrated device mastery prior to training on Spiromax(R) compared with 20 (4%) on Turbuhaler(R) (p < 0.001). The median number of training steps required to achieve mastery was 2 (interquartile range [IQR] 2-4) for Spiromax(R) and 3 (IQR 2-4) for Turbuhaler(R) (p < 0.001). A higher number of participants maintained mastery with Spiromax(R) compared with Turbuhaler(R), at visits 2 and 3 (64% vs 41% and 79% vs 65%, respectively; p < 0.001). CONCLUSIONS: There are significant differences in the nature and extent of training required to achieve and maintain mastery for Spiromax(R) and Turbuhaler(R) devices. The implications on clinical practice, device education delivery, and patient outcomes require further evaluation.

Published
2018

8. Letters to the Editor

Author

Hedges, Kenneth, Rozovsky, L.E., Rozovsky, F.A., Davis, J. B., Rand, C. G., and Chambers, Larry W.

Published
1982

16. C-B4-03: Promoting Adherence to Improve Effectiveness of Cardiovascular Disease Therapies (PATIENT): Implementing a Medication Adherence Intervention Using Health Information Technology

Author

Vollmer, W., primary, Williams, A., additional, Vupputuri, S., additional, Rand, C., additional, Smith, D., additional, Feldstein, A., additional, Ditmer, D., additional, Tom, J., additional, Laws, R., additional, Schneider, J., additional, Waterbury, A., additional, Owen-Smith, A., additional, and Yonehara, C., additional

Published
2011
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19. Cancer Diagnostic Assessment Programs: Standards for the Organization of Care in Ontario

Author

Brouwers, M., primary, Oliver, T. K., additional, Crawford, J., additional, Ellison, P., additional, Evans, W. K., additional, Gagliardi, A., additional, Lacourciere, J., additional, Lo, D., additional, Mai, V., additional, McNair, S., additional, Minuk, T., additional, Rabeneck, L., additional, Rand, C., additional, Ross, J., additional, Smylie, J., additional, Srigley, J., additional, Stern, H., additional, and Trudeau, M., additional

Published
2009
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27. Europe

Author

RAND C. LEWIS

Subjects
Sociology and Political Science, General Social Sciences
Published
1992

28. COCOM: An International Attempt to Control Technology

Author

DEFENSE INST OF SECURITY ASSISTANCE MANAGEMENT WRIGHT-PATTERSON AFB OH, Lewis, Rand C., DEFENSE INST OF SECURITY ASSISTANCE MANAGEMENT WRIGHT-PATTERSON AFB OH, and Lewis, Rand C.

Abstract

The changes in Eastern Europe have precipitated a rapid re-evaluation of export control efforts on the part of the Western Allies. This is best evidenced by recent high level meetings in Paris between the participants of the Coordination Committee for Multilateral Export Controls (COCOM). The results of these meetings are extremely important to the future of multi-national methods of technology control. COCOM was established in 1949 as a response by members of NATO to the growing Soviet threat. Seven western European nations, plus the United States, determined there was a need for the multilateral control of military technology available to the Soviets and their surrogate East Bloc states. The concept was to deny the export of strategic technology to the Warsaw Pact in order to deny access to technologies that increased the effectiveness of their respective militaries.1, Pub in The DISAM Journal, v13 Issue 1 p.66-73, Fall 1990.

Published
1990

36. Hybrid incoherent optical pattern recognition system

Author

Sherman, Rand C., Grieser, Daniel, Gamble, F. Trevor, Verber, Carl M., and Dolash, Thomas

Abstract

A pattern recognition system that uses incoherent spatial filtering to recognize images directly from a narrowband phosphor television monitor is described. Images of real objects are captured with a television camera. These images are then edge-enhanced electronically and displayed on the TV monitor. The monitor output is used directly as the input to a holographic correlator. An optical multichannel analyzer at the correlation plane is used to analyze the shape of the correlation function and to determine the position of its peak. Experimental results agree well with theory. Concepts for handling rotation, aspect angle, and scale variations of the input are discussed.

Published
1983

37. A method for the epidemiologic study of early diabetes

Author

Rand, C. G., Jackson, R. J. D., and Mackie, C. C.

Subjects
Adult, Blood Glucose, Male, Ontario, Surveys and Questionnaires, Diabetes Mellitus, Humans, Mass Screening, Female, Original Articles, Glucose Tolerance Test, Middle Aged, Aged
Abstract

A diabetic survey was conducted among 4048 subjects well enough to report for work, using a questionnaire covering past, present, family and obstetric history, and a capillary blood glucose determination at least 1(1/2) hours after eating. A "positive screen" was obtained in 267 individuals, in 67 on the basis of elevated blood glucose value alone, in 179 on the basis of questionnaire responses alone, and in 21 by both criteria. Glucose tolerance tests were performed on 130 subjects (49% of eligible individuals) and yielded diabetic curves in 18, 6 and 33% respectively for the three categories of positive screening tests.It is suggested that the magnitude of the group with positive history only is such that future natural history studies must take this subsample into consideration.

Published
1974

38. Study of the Twophoton Photorefractive Effect in Lithium Niobate

Author

BATTELLE COLUMBUS LABS OH, Wood,Van E, Verber,Carl M, Sherman,Rand C, Hartman,Nile F, BATTELLE COLUMBUS LABS OH, Wood,Van E, Verber,Carl M, Sherman,Rand C, and Hartman,Nile F

Abstract

The dynamics and wavelength dependence of recording and optical erasure of thick phase gratings produced photorefractively were studied in undoped and in iron-doped lithium niobate. Properties of gratings formed at high incident power densities via two-photon absorption were compared with those of gratings formed at shorter wavelengths by the usual one-photon mechanism. Gratings formed by the two-photon mechanism in undoped crystals exhibit a distinctive two-exponential time dependence of optical erasure not observed in other circumstances. This shows that the nature of final trap states, as well as absorption and charge transfer characteristics, is important in controlling photorefractive sensitivity. A method was discovered for producing high diffraction efficiency gratings at infrared frequencies in titanium-diffused optical waveguides on lithium niobate. (Author)

Published
1981

39. Optical Waveguide Scattering Reduction. II.

Author

BATTELLE COLUMBUS LABS OH, Vahey,David W, Hartman,Nile F, Sherman,Rand C, BATTELLE COLUMBUS LABS OH, Vahey,David W, Hartman,Nile F, and Sherman,Rand C

Abstract

The goal of this program was the reduction of scattering in optical waveguides to levels commensurate with 40 dB dynamic range for an integrated optical spectrum analyzer. Waveguides formed by thermal diffusion of Ti films into LiNbO3 substrates were emphasized. Nine potential sources of scattering in such waveguides were identified and discussed. Diagnostic methods and optical scattering experiments useful for studying the sources of scattering were described and experimental results for non-scattering experiments were presented. An analysis of the effects of Rayleigh, Rayleigh-Gans-Debye, and Mie scattering on spectrum analyzer dynamic range was performed. Formulas for differential scattering cross sections were derived, and parameter values for various sources of scattering were inserted to obtain estimates of spectrum-analyzer performance for each scattering mechanism. Rayleigh-Gans-Debye scattering centers from surface roughness and surface compounds (probably Li-Ti-O compounds) were found to lead to the largest predicted scattering. Experimental in-plane scattered-energy distributions were complicated by the effects of prism-enhanced scattering, which was theoretically investigated. Data were obtained using either end-fire input coupling or by comparing the scattering generated using two different input-output coupling-prism separations. The best performance achieved was consistent with scattering from either surface roughness or surface-compound formation. The performance was consistent with a spectrum-analyzer dynamic range of only 27 dB.

Published
1980

40. Numerical Modeling of Contaminant Transport with Rate-Limited Sorption/Desorption in an Aquifer.

Author

AIR FORCE INST OF TECH WRIGHT-PATTERSON AFB OH SCHOOL OF ENGINEERING, Huso, Rand C, AIR FORCE INST OF TECH WRIGHT-PATTERSON AFB OH SCHOOL OF ENGINEERING, and Huso, Rand C

Abstract

Years of accidental or deliberate dumping of petroleum products and hazardous waste materials has resulted in polluted groundwater. The Department of Defense is engaged in a massive program, known as the Installation Restoration Program, to cleanup these polluted environments on military installations, and the Environmental Protection Agency is funding research to help in the cleanup efforts. These cleanup efforts often involve drilling wells in the vicinity of the contaminated area and evacuating water until the concentration of pollutant is reasonably low. The planners at these remediation sites use tools to estimate how long the wells must operate based on some initial sample data and sound judgement. (jes)

Published
1989

41. TULARÆMIA

Author

Rand, C. G.

Subjects
Humans, Articles, Tularemia
Published
1949

43. Normal distributions

Author

Rand, C G

Subjects
Correspondence, General Engineering, General Earth and Planetary Sciences, General Medicine, General Environmental Science
Published
1976

45. Comparison of pharmacy-based measures of medication adherence

Author

Vollmer William M, Xu Maochao, Feldstein Adrianne, Smith David, Waterbury Amy, and Rand Cynthia

Subjects
Asthma, Inhaled corticosteroids, Adult, Medication adherence, Randomized clinical trial, Methodology, Public aspects of medicine, RA1-1270
Abstract

Abstract Background Pharmacy databases are commonly used to assess medication usage, and a number of measures have been developed to measure patients’ adherence to medication. An extensive literature now supports these measures, although few studies have systematically compared the properties of different adherence measures. Methods As part of an 18-month randomized clinical trial to assess the impact of automated telephone reminders on adherence to inhaled corticosteroids (ICS) among 6903 adult members of a managed care organization, we computed eight pharmacy-based measures of ICS adherence using outpatient pharmacy dispensing records obtained from the health plan’s electronic medical record. We used simple descriptive statistics to compare the relative performance characteristics of these measures. Results Comparative analysis found a relative upward bias in adherence estimates for those measures that require at least one dispensing event to be calculated. Measurement strategies that require a second dispensing event evidence even greater upward bias. These biases are greatest with shorter observation times. Furthermore, requiring a dispensing to be calculated meant that these measures could not be defined for large numbers of individuals (17-32 % of participants in this study). Measurement strategies that do not require a dispensing event to be calculated appear least vulnerable to these biases and can be calculated for everyone. However they do require additional assumptions and data (e.g., pre-intervention dispensing data) to support their validity. Conclusions Many adherence measures require one, or sometimes two, dispensings in order to be defined. Since such measures assume all dispensed medication is used as directed, they have a built in upward bias that is especially pronounced when they are calculated over relatively short timeframes (< 9 months). Less biased measurement strategies that do not require a dispensing event are available, but require additional data to support their validity. Trial registration The study was funded by grant R01HL83433 from the National Heart, Lung and Blood Institute (NHLBI) and is filed as study NCT00414817 in the clinicaltrials.gov database.

Published
2012
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46. Effective interventions to facilitate the uptake of breast, cervical and colorectal cancer screening: an implementation guideline

Author

Brouwers Melissa C, De Vito Carol, Bahirathan Lavannya, Carol Angela, Carroll June C, Cotterchio Michelle, Dobbins Maureen, Lent Barbara, Levitt Cheryl, Lewis Nancy, McGregor S Elizabeth, Paszat Lawrence, Rand Carol, and Wathen Nadine

Subjects
Medicine (General), R5-920
Abstract

Abstract Background Appropriate screening may reduce the mortality and morbidity of colorectal, breast, and cervical cancers. Several high-quality systematic reviews and practice guidelines exist to inform the most effective screening options. However, effective implementation strategies are warranted if the full benefits of screening are to be realized. We developed an implementation guideline to answer the question: What interventions have been shown to increase the uptake of cancer screening by individuals, specifically for breast, cervical, and colorectal cancers? Methods A guideline panel was established as part of Cancer Care Ontario's Program in Evidence-based Care, and a systematic review of the published literature was conducted. It yielded three foundational systematic reviews and an existing guidance document. We conducted updates of these reviews and searched the literature published between 2004 and 2010. A draft guideline was written that went through two rounds of review. Revisions were made resulting in a final set of guideline recommendations. Results Sixty-six new studies reflecting 74 comparisons met eligibility criteria. They were generally of poor to moderate quality. Using these and the foundational documents, the panel developed a draft guideline. The draft report was well received in the two rounds of review with mean quality scores above four (on a five-point scale) for each of the items. For most of the interventions considered, there was insufficient evidence to support or refute their effectiveness. However, client reminders, reduction of structural barriers, and provision of provider assessment and feedback were recommended interventions to increase screening for at least two of three cancer sites studied. The final guidelines also provide advice on how the recommendations can be used and future areas for research. Conclusion Using established guideline development methodologies and the AGREE II as our methodological frameworks, we developed an implementation guideline to advise on interventions to increase the rate of breast, cervical and colorectal cancer screening. While advancements have been made in these areas of implementation science, more investigations are warranted.

Published
2011
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47. What implementation interventions increase cancer screening rates? a systematic review

Author

Lent Barbara, Dobbins Maureen, Cotterchio Michelle, Carroll June C, Carol Angela, Bahirathan Lavannya, De Vito Carol, Brouwers Melissa C, Levitt Cheryl, Lewis Nancy, McGregor S Elizabeth, Paszat Lawrence, Rand Carol, and Wathen Nadine

Subjects
Medicine (General), R5-920
Abstract

Abstract Background Appropriate screening may reduce the mortality and morbidity of colorectal, breast, and cervical cancers. However, effective implementation strategies are warranted if the full benefits of screening are to be realized. As part of a larger agenda to create an implementation guideline, we conducted a systematic review to evaluate interventions designed to increase the rate of breast, cervical, and colorectal cancer (CRC) screening. The interventions considered were: client reminders, client incentives, mass media, small media, group education, one-on-one education, reduction in structural barriers, reduction in out-of-pocket costs, provider assessment and feedback interventions, and provider incentives. Our primary outcome, screening completion, was calculated as the overall median post-intervention absolute percentage point (PP) change in completed screening tests. Methods Our first step was to conduct an iterative scoping review in the research area. This yielded three relevant high-quality systematic reviews. Serving as our evidentiary foundation, we conducted a formal update. Randomized controlled trials and cluster randomized controlled trials, published between 2004 and 2010, were searched in MEDLINE, EMBASE and PSYCHinfo. Results The update yielded 66 studies new eligible studies with 74 comparisons. The new studies ranged considerably in quality. Client reminders, small media, and provider audit and feedback appear to be effective interventions to increase the uptake of screening for three cancers. One-on-one education and reduction of structural barriers also appears effective, but their roles with CRC and cervical screening, respectively, are less established. More study is required to assess client incentives, mass media, group education, reduction of out-of-pocket costs, and provider incentive interventions. Conclusion The new evidence generally aligns with the evidence and conclusions from the original systematic reviews. This review served as the evidentiary foundation for an implementation guideline. Poor reporting, lack of precision and consistency in defining operational elements, and insufficient consideration of context and differences among populations are areas for additional research.

Published
2011
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48. Study design and participant characteristics of a randomized controlled trial of directly administered antiretroviral therapy in opioid treatment programs

Author

Glass Sheldon, McCaul Mary E, Galai Noya, Rand Cynthia, Moore Richard D, Cook Katie, Mullen Bernadette, Oursler Krisann K, and Lucas Gregory M

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background HIV-infected drug users are at higher risk of non-adherence and poor treatment outcomes than HIV-infected non-drug users. Prior work from our group and others suggests that directly administered antiretroviral therapy (DAART) delivered in opioid treatment programs (OTPs) may increase rates of viral suppression. Methods/Design We are conducting a randomized trial comparing DAART to self-administered therapy (SAT) in 5 OTPs in Baltimore, Maryland. Participants and investigators are aware of treatment assignments. The DAART intervention is 12 months. The primary outcome is HIV RNA < 50 copies/mL at 3, 6, and 12 months. To assess persistence of any study arm differences that emerge during the active intervention, we are conducting an 18-month visit (6 months after the intervention concludes). We are collecting electronic adherence data for 2 months in both study arms. Of 457 individuals screened, a total of 107 participants were enrolled, with 56 and 51 randomly assigned to DAART and SAT, respectively. Participants were predominantly African American, approximately half were women, and the median age was 47 years. Active use of cocaine and other drugs was common at baseline. HIV disease stage was advanced in most participants. The median CD4 count at enrollment was 207 cells/mm3, 66 (62%) had a history of an AIDS-defining opportunistic condition, and 21 (20%) were antiretroviral naïve. Conclusions This paper describes the rationale, methods, and baseline characteristics of subjects enrolled in a randomized clinical trial comparing DAART to SAT in opioid treatment programs. Trial Registration ClinicalTrials.gov: NCT00279110

Published
2011
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49. Improved adherence with once-daily versus twice-daily dosing of mometasone furoate administered via a dry powder inhaler: a randomized open-label study

Author

Rand Cynthia, Bullen Kevin, Robertson Anne, Price David, Horne Rob, and Staudinger Heribert

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Abstract Background Poor adherence with prescribed asthma medication is a major barrier to positive treatment outcomes. This study was designed to determine the effect of a once-daily administration of mometasone furoate administered via a dry powder inhaler (MF-DPI) on treatment adherence compared with a twice-daily administration. Methods This was a 12-week open-label study designed to mimic an actual clinical setting in patients ≥12 years old with mild-to-moderate persistent asthma. Patients were randomized to receive MF-DPI 400 μg once-daily in the evening or MF-DPI 200 μg twice-daily. Adherence was assessed primarily using the number of actual administered doses reported from the device counter divided by the number of scheduled doses. Self-reports were also used to determine adherence. Health-related quality of life, healthcare resource utilization, and days missed from work or school were also reported. Results 1233 patients were randomized. The mean adherence rates, as measured by the automatic dose counter, were significantly better (P < 0.001) with MF-DPI 400 μg once-daily in the evening (93.3%) than with MF-DPI 200 μg twice-daily (89.5%). Mean adherence rates based on self-reports were also significantly better (P < 0.001) with MF-DPI 400 μg QD PM (97.2%) than with MF-DPI 200 μg twice-daily (95.3%). Adherence rates were lower in adolescents (12-17 years old). Health-related quality of life improved by 20% in patients using MF-DPI once-daily in the evening and by 14% in patients using MF-DPI twice-daily. Very few ( Conclusion Mean adherence rates were greater with a once-daily dosing regimen of MF-DPI than with a twice-daily dosing regimen. This trial was completed prior to the ISMJE requirements for trial registration.

Published
2010
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50. A cohort study of possible risk factors for over-reporting of antihypertensive adherence

Author

Lee Mei-Ling Ting, Inui Thomas S, Rand Cynthia S, Choo Peter W, Canning Claire, and Platt Richard

Subjects
Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Background The identification of poor medicinal adherence is difficult because direct observation of medication use is usually impractical. Up to 50% of individuals on chronic therapies may not be taking their medication as prescribed. This study is one of the first to explore possible risk factors for over-reporting of antihypertensive adherence using electronic medication monitoring. Methods The adherence of 286 individuals on single-drug antihypertensive therapy in a large managed care organization was electronically monitored for approximately three months. Questionnaires on socioeconomic background, adherence to therapy, health beliefs, and social support before and after adherence monitoring were completed. Over-reporting of antihypertensive adherence was assessed by comparing the self-reported frequency of noncompliance with that determined from electronic dosing records. Risk factors for over-reporting were identified by contingency table analysis and step-wise logistic regression. Results Although only 21% of participants acknowledged missing doses on one or more days per week, electronic monitoring documented nonadherence at this or a higher level in 42% of participants. The following variables were associated with over-reporting: >1 versus 1 daily dose (OR = 2.58; 95% CI = 1.50–4.41; p = .0006), lower perceived health risk from nonadherence (OR = 1.35; 95% CI = 1.10–1.64; p = .0035), and annual household income of $30,000 (OR = 2.64; 95% CI = 1.13–6.18; p = .025). Conclusions Over-reporting of adherence may be affected by factors related to dosing frequency, health beliefs and socioeconomic status. This topic deserves further investigation in other patient populations to elucidate possible underlying behavioral explanations.

Published
2001
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