1,300 results on '"Angus B"'
Search Results
252. Is environmental antimony a potential health problem?
- Author
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Farmer, John G., Cloy, Joanna M., Graham, Margaret C., MacKenzie, Angus B., and Cook, Gordon T.
- Published
- 2006
- Full Text
- View/download PDF
253. High temperature superconducting infrared imaging satellite
- Author
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Angus, B, Covelli, J, Davinic, N, Hailey, J, Jones, E, Ortiz, V, Racine, J, Satterwhite, D, Spriesterbach, T, and Sorensen, D
- Subjects
Spacecraft Design, Testing And Performance - Abstract
A low earth orbiting platform for an infrared (IR) sensor payload is examined based on the requirements of a Naval Research Laboratory statement of work. The experiment payload is a 1.5-meter square by 0.5-meter high cubic structure equipped with the imaging system, radiators, and spacecraft mounting interface. The orbit is circular at 509 km (275 nmi) altitude and 70 deg. inclination. The spacecraft is three-axis stabilized with pointing accuracy of plus or minus 0.5 deg. in each axis. The experiment payload requires two 15-minute sensing periods over two contiguous orbit periods for 30 minutes of sensing time per day. The spacecraft design is presented for launch via a Delta 2 rocket. Subsystem designs include attitude control, propulsion, electric power, telemetry, tracking and command, thermal design, structure, and cost analysis.
- Published
- 1992
254. Comparison of an ordinal endpoint to time-to-event, longitudinal, and binary endpoints for use in evaluating treatments for severe influenza requiring hospitalization
- Author
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Peterson, R, Vock, D, Babiker, A, Powers, J, Hunsberger, S, Angus, B, Paez, A, Neaton, J, and Group, Insight Flu-Ivig Study
- Subjects
medicine.medical_specialty ,Proportional odds model ,Disease ,Severe influenza ,Placebo group ,Article ,Statistical power ,Food and drug administration ,03 medical and health sciences ,Clinical trials ,0302 clinical medicine ,Outcome assessments ,medicine ,030212 general & internal medicine ,Event (probability theory) ,Pharmacology ,lcsh:R5-920 ,business.industry ,General Medicine ,3. Good health ,Clinical trial ,Emergency medicine ,Endpoints ,Ordered logit ,lcsh:Medicine (General) ,business ,030217 neurology & neurosurgery - Abstract
Background/aims: The Food and Drug Administration recommends research into developing well-defined and reliable endpoints to evaluate treatments for severe influenza requiring hospitalization. A novel 6-category ordinal endpoint of patient health status after 7 days that ranges from death to hospital discharge with resumption of normal activities is being used in a randomized placebo-controlled trial of intravenous immunoglobulin (IVIG) for severe influenza (FLU-IVIG). We compare the power of the ordinal endpoint under a proportional odds model to other types of endpoints as a function of various trial parameters. Methods: We used closed-form analysis and empirical simulation to compare the power of the ordinal endpoint to time-to-event, longitudinal, and binary endpoints. In the simulation setting, we varied the treatment effect and the distribution of the placebo group across the follow-up period with consideration of adjustment for baseline health status. Results: In the analytic setting, ordinal endpoints of high granularity provided greater power than time-to-event endpoints when most patients in the placebo group had either naturally progressed to the category of hospital discharge by day 7 or were far from hospital discharge on day 7. In the simulation setting, adjustment for baseline health status universally raised power for the proportional odds model. Across different placebo group distributions of the ordinal endpoint regardless of adjustment for baseline health status, only time-to-event endpoints yielded higher power than the ordinal endpoint for certain treatment effects. Conclusions: In this case study, the FLU-IVIG ordinal endpoint provided greater power than time-to-event, binary, and longitudinal endpoints for most scenarios of the treatment effect and placebo group distribution, including the target population studied for FLU-IVIG. The ordinal endpoint was only surpassed by the time-to-event endpoint when many patients in the placebo group were on the cusp of hospital discharge on day 7 and the follow-up period for the time-to-event endpoint was extended to allow for additional events. Our general approach for evaluating the power of several potential endpoints for an influenza trial can be used for designing other influenza trials with different target populations and for other trials in other disease areas. Keywords: Clinical trials, Endpoints, Outcome assessments, Proportional odds model, Statistical power
- Published
- 2019
- Full Text
- View/download PDF
255. Application of a challenge model to assess the protective efficacy of oral typhoid vaccines in humans
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Darton, T, Pollard, A, Angus, B, Pollard, A, and Angus, B
- Subjects
Vaccines - Abstract
Human infection by Salmonella Typhi has been occurring for the last 50,000 years and still accounts for ∼ 22million new cases each year worldwide. Through faeco-oral transmission, this human-restricted infection disproportionately affects the most impoverished sections of endemic communities where adequate sanitation infrastructure and effective vaccination approaches are lacking. Development of new control measures to accurately measure the burden of disease and to prevent infection with new vaccine candidates are hindered by an incomplete understanding of host-pathogen interactions and of what constitutes a protective human response after exposure. In this thesis I describe the practical application of a recently developed human challenge model of typhoid infection in assessing new control measures, including the evaluation of the oral single-dose vaccine candidate, M01ZH09. In performing a large, double-blind, placebo-controlled study, I was able to measure the direct protective efficacy (PE) of vaccination with either M01ZH09 or 3-dose Ty21a by performing human challenge with 104CFU Salmonella Typhi, Quailes strain, 28-days later. Using clinical and microbiological definitions to confirm typhoid diagnosis during a 14-day period after ingestion, I found insignificant levels of protection afforded by a single dose of M01ZH09 (12.9%), and a low PE after Ty21a vaccination (35%), demonstrating the stringency of the model and the endpoints used. Many additional insights into pathogen dynamics and host responses were found highlighting several important characteristics of oral vaccination. M01ZH09 was highly immunogenic, and both active vaccines significantly reduced bacterial burden (bacteraemia and stool shedding) while having no effect on symptomatic severity of infection in those diagnosed. M01ZH09 receipt resulted in a significantly longer incubation period, suggesting underlying protective responses were being generated. Further findings included the first objective demonstration of primary bacteraemia occurring after typhoid exposure, and frequent asymptomatic infection or stool shedding in those exposed but remaining well. Overall, these data also demonstrated significant protective effects against challenge by anti-Vi antibody status and age at baseline. Taking these factors into account, M01ZH09 and Ty21a vaccination did convey an overall protective advantage against developing typhoid infection, each reducing the risk of diagnosis by ~two-fold during the challenge period.
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- 2015
256. Circulating microRNAs in Sera Correlate with Soluble Biomarkers of Immune Activation but Do Not Predict Mortality in ART Treated Individuals with HIV-1 Infection: A Case Control Study
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Murray, D. D., Suzuki, K., Law, M., Trebicka, J., Neuhaus, J., Wentworth, D., Johnson, M., Vjecha, M. J., Kelleher, A. D., Emery, S., Aagaard, B., Aragon, E., Arnaiz, J., Borup, L., Clotet, B., Dragsted, U., Fau, A., Gey, D., Grarup, J., Hengge, U., Herrero, P., Jansson, P., Jensen, B., Jensen, K., Juncher, H., Lopez, P., Lundgren, J. D., Matthews, C., Mollerup, D., Pearson, M., Phillips, A., Reilev, S., Tillmann, K., Varea, S., Angus, B., Babiker, A., Cordwell, B., Darbyshire, J., Dodds, W., Fleck, S., Horton, J., Hudson, F., Moraes, Y., Pacciarini, F., Palfreeman, A., Paton, N., Smith, N., Van Hooff, F., Bebchuk, J., Collins, G., Denning, E., Duchene, A., Fosdick, L., Harrison, M., Herman-Lamin, K., Krum, E., Larson, G., Neaton, J., Nelson, R., Quan, K., Quan, S., Schultz, T., Thompson, G., Wyman, N., Carey, C., Chan, F., Cooper, D., Courtney-Rodgers, D., Drummond, F., Harrod, M., Jacoby, S., Kearney, L., Lin, E., Pett, S., Robson, R., Seneviratne, N., Stewart, M., Watts, E., Finley, E., Gordin, F., Sanchez, A., Standridge, B., Belloso, W., Davey, R., Duprez, D., Gatell, J., Hoy, J., Lifson, A., Pederson, C., Perez, G., Price, R., Prineas, R., Rhame, F., Sampson, J., Worley, J., Modlin, J., Beral, V., Chaisson, R., Fleming, T., Hill, C., Kim, K., Murray, B., Pick, B., Seligmann, M., Weller, I., Cahill, K., Fox, L., Luzar, M., Martinez, A., Mcnay, L., Pierson, J., Tierney, J., Vogel, S., Costas, V., Eckstrand, J., Brown, S., Abusamra, L., Angel, E., Aquilia, S., Benetucci, J., Bittar, V., Bogdanowicz, E., Cahn, P., Casiro, A., Contarelli, J., Corral, J., Daciuk, L., David, D., Dobrzanski, W., Duran, A., Ebenrstejin, J., Ferrari, I., Fridman, D., Galache, V., Guaragna, G., Ivalo, S., Krolewiecki, A., Lanusse, I., Laplume, H., Lasala, M., Lattes, R., Lazovski, J., Lopardo, G., Losso, M., Lourtau, L., Lupo, S., Maranzana, A., Marson, C., Massera, L., Moscatello, G., Olivia, S., Otegui, I., Palacios, L., Parlante, A., Salomon, H., Sanchez, M., Somenzini, C., Suarez, C., Tocci, M., Toibaro, J., Zala, C., Agrawal, S., Ambrose, P., Anderson, C., Anderson, J., Baker, D., Beileiter, K., Blavius, K., Bloch, M., Boyle, M., Bradford, D., Britton, P., Brown, P., Busic, T., Cain, A., Carrall, L., Carson, S., Chenoweth, I., Chuah, J., Clark, F., Clemons, J., Clezy, K., Cortissos, P., Cunningham, N., Curry, M., Daly, L., D'Arcy-Evans, C., Del Rosario, R., Dinning, S., Dobson, P., Donohue, W., Doong, N., Downs, C., Edwards, E., Edwards, S., Egan, C., Ferguson, W., Finlayson, R., Forsdyke, C., Foy, L., Franic, T., Frater, A., French, M., Gleeson, D., Gold, J., Habel, P., Haig, K., Hardy, S., Holland, R., Hudson, J., Hutchison, R., Hyland, N., James, R., Johnston, C., Kelly, M., King, M., Kunkel, K., Lau, H., Leamy, J., Lester, D., Leung, J., Lohmeyer, A., Lowe, K., Macrae, K., Magness, C., Martinez, O., Maruszak, H., Medland, N., Miller, S., Murray, J., Negus, P., Newman, R., Ngieng, M., Nowlan, C., Oddy, J., Orford, N., Orth, D., Patching, J., Plummer, M., Price, S., Primrose, R., Prone, I., Ree, H., Remington, C., Richardson, R., Robinson, S., Rogers, G., Roney, J., Roth, N., Russell, D., Ryan, S., Sarangapany, J., Schmidt, T., Schneider, K., Shields, C., Silberberg, C., Shaw, D., Skett, J., Smith, D., Soo, T. M., Sowden, D., Street, A., Tee, B. K., Thomson, J., Topaz, S., Vale, R., Villella, C., Walker, A., Watson, A., Wendt, N., Williams, L., Youds, D., Aichelburg, A., Cichon, P., Gemeinhart, B., Rieger, A., Schmied, B., Touzeau-Romer, V., Vetter, N., Colebunders, R., Clumeck, N., Deroo, A., Kabeya, K., O'Doherty, E., De Wit, S., De Salles Amorim, C., Basso, C., Flint, S., Kallas, E., Levi, G., Lewi, D., Pereira, L., Da Silva, M., Souza, T., Toscano, A., Angel, J., Arsenault, M., Bast, M., Beckthold, B., Bouchard, P., Chabot, I., Clarke, R., Cohen, J., Cote, P., Ellis, M., Gagne, C., Gill, J., Houde, M., Johnston, B., Jubinville, N., Kato, C., Lamoureux, N., Latendre-Paquette, J., Lindemulder, A., Mcneil, A., Mcfarland, N., Montaner, J., Morrisseau, C., O'Neill, R., Page, G., Piche, A., Pongracz, B., Preziosi, H., Puri, L., Rachlis, A., Ralph, E., Raymond, I., Rouleau, D., Routy, J. P., Sandre, R., Seddon, T., Shafran, S., Sikora, C., Smaill, F., Stromberg, D., Trottier, S., Walmsley, S., Weiss, K., Williams, K., Zarowny, D., Baadegaard, B., Andersen, A. B., Boedker, K., Collins, P., Gerstoft, J., Jensen, L., Moller, H., Andersen, P. L., Loftheim, I., Mathiesen, L., Nielsen, H., Obel, N., Pedersen, C., Petersen, D., Jensen, L. P., Black, F. T., Aboulker, J. P., Aouba, A., Bensalem, M., Berthe, H., Blanc, C., Bornarel, D., Bouchaud, O., Boue, F., Bouvet, E., Brancon, C., Breaud, S., Brosseau, D., Brunet, A., Capitant, C., Ceppi, C., Chakvetadze, C., Cheneau, C., Chennebault, J. M., De Truchis, P., Delavalle, A. M., Delfraissy, J. F., Dellamonica, P., Dumont, C., Edeb, N., Fabre, G., Ferrando, S., Foltzer, A., Foubert, V., Gastaut, J. A., Gerbe, J., Girard, P. M., Goujard, C., Hoen, B., Honore, P., Hue, H., Hynh, T., Jung, C., Kahi, S., Katlama, C., Lang, J. M., Le Baut, V., Lefebvre, B., Leturque, N., Levy, Y., Loison, J., Maddi, G., Maignan, A., Majerholc, C., De Boever, C., Meynard, J. L., Michelet, C., Michon, C., Mole, M., Netzer, E., Pialoux, G., Poizot-Martin, I., Raffi, F., Ratajczak, M., Ravaux, I., Reynes, J., Salmon-Ceron, D., Sebire, M., Simon, A., Tegna, L., Tisne-Dessus, D., Tramoni, C., Viard, J. P., Vidal, M., Viet-Peaucelle, C., Weiss, L., Zeng, A., Zucman, D., Adam, A., Arasteh, K., Behrens, G., Bergmann, F., Bickel, M., Bittner, D., Bogner, J., Brockmeyer, N., Darrelmann, N., Deja, M., Doerler, M., Esser, S., Faetkenheuer, G., Fenske, S., Gajetzki, S., Goebel, F., Gorriahn, D., Harrer, E., Harrer, T., Hartl, H., Hartmann, M., Heesch, S., Jakob, W., Jager, H., Klinker, H., Kremer, G., Ludwig, C., Mantzsch, K., Mauss, S., Meurer, A., Niedermeier, A., Pittack, N., Plettenberg, A., Potthoff, A., Probst, M., Rittweger, M., Rockstroh, J., Ross, B., Rotty, J., Rund, E., Ruzicka, T., Schmidt, R., Schmutz, G., Schnaitmann, E., Schuster, D., Sehr, T., Spaeth, B., Staszewski, S., Stellbrink, H. J., Stephan, C., Stockey, T., Stoehr, A., Trein, A., Vaeth, T., Vogel, M., Wasmuth, J., Wengenroth, C., Winzer, R., Wolf, E., Mulcahy, F., Reidy, D., Cohen, Y., Drora, G., Eliezer, I., Godo, O., Kedem, E., Magen, E., Mamorsky, M., Pollack, S., Sthoeger, Z., Vered, H., Yust, I., Aiuti, F., Bechi, M., Bergamasco, A., Bertelli, D., Bruno, R., Butini, L., Cagliuso, M., Carosi, G., Casari, S., Chrysoula, V., Cologni, G., Conti, V., Costantini, A., Corpolongo, A., D'Offizi, G., Gaiottino, F., Di Pietro, M., Esposito, R., Filice, G., Francesco, M., Gianelli, E., Graziella, C., Magenta, L., Martellotta, F., Maserati, R., Mazzotta, F., Murdaca, G., Nardini, G., Nozza, S., Puppo, F., Pogliaghi, M., Ripamonti, D., Ronchetti, C., Rusconi, S., Rusconi, V., Sacchi, P., Silvia, N., Suter, F., Tambussi, G., Uglietti, A., Vechi, M., Vergani, B., Vichi, F., Vitiello, P., Iwamoto, A., Kikuchi, Y., Miyazaki, N., Mori, M., Nakamura, T., Odawara, T., Oka, S., Shirasaka, T., Tabata, M., Takano, M., Ueta, C., Watanabe, D., Yamamoto, Y., Erradey, I., Himmich, H., El Filali, K. M., Blok, W., Van Boxtel, R., Doevelaar, K. B. H., Van Eeden, A., Grijsen, M., Groot, M., Juttmann, J., Kuipers, M., Ligthart, S., Van Der Meulen, P., Lange, J., Langebeek, N., Reiss, P., Richter, C., Schoemaker, M., Schrijnders-Gudde, L., Septer-Bijleveld, E., Sprenger, H., Vermeulen, J., Ten Kate, R., Van De Ven, B., Bruun, J., Kvale, D., Maeland, A., Bakowska, E., Beniowski, M., Boron-Kaczmarska, A., Gasiorowski, J., Horban, A., Inglot, M., Knysz, B., Mularska, E., Parczewski, M., Pynka, M., Rymer, W., Szymczak, A., Aldir, M., Antunes, F., Baptista, C., Da Conceicao Vera, J., Doroana, M., Mansinho, K., Dos Santos, C. R. A., Valadas, E., Vaz Pinto, I., Chia, E., Foo, E., Karim, F., Lim, P. L., Panchalingam, A., Quek, A., Alcazar-Caballero, R., Arribas, J., Arrizabalaga, J., De Barron, X., Blanco, F., Bouza, E., Bravo, I., Calvo, S., Carbonero, L., Carpena, I., Castro, M., Cortes, L., Del Toro, M., Domingo, P., Elias, M., Espinosa, J., Estrada, V., Fernandez-Cruz, E., Fernandez, P., Freud, H., Fuster, M., Garcia, A., Garcia, G., Garrido, R., Gijon, P., Gonzalez-Garcia, J., Gil, I., Gonzalez, A., Gonzalez-Lahoz, J., Grosso, P. L., Gutierrez, M., Guzman, E., Iribarren, J., Jimenez, M., Jou, A., Juega, J., Lopez, J., Lozano, F., Martin-Carbonero, L., Mata, R., Mateo, G., Menasalvas, A., Mirelles, C., De Miguel Prieto, J., Montes, M., Moreno, A., Moreno, J., Moreno, V., Munoz, R., Ocampo, A., Ortega, E., Ortiz, L., Padilla, B., Parras, A., Paster, A., Pedreira, J., Pena, J., Perea, R., Portas, B., Puig, J., Pulido, F., Rebollar, M., De Rivera, J., Roca, V., Rodriguez-Arrondo, F., Rubio, R., Santos, J., Sanz, J., Sebastian, G., Segovia, M., Soriano, V., Tamargo, L., Viciana, P., Von Wichmann, M., Bratt, G., Hollander, A., Olov Pehrson, P., Petz, I., Sandstrom, E., Sonnerborg, A., Bernasconi, E., Gurtner, V., Ampunpong, U., Auchieng, C., Bowonwatanuwong, C., Chanchai, P., Chetchotisakd, P., Chuenyan, T., Duncombe, C., Horsakulthai, M., Kantipong, P., Laohajinda, K., Phanuphak, P., Pongsurachet, V., Pradapmook, S., Ruxruntham, K., Seekaew, S., Sonjai, A., Suwanagool, S., Techasathit, W., Ubolyam, S., Wankoon, J., Alexander, I., Dockrell, D., Easterbrook, P., Edwards, B., Evans, E., Fisher, M., Fox, R., Gazzard, B., Gilleran, G., Hand, J., Heald, L., Higgs, C., Jebakumar, S., Jendrulek, I., Johnson, S., Kinghorn, G., Kuldanek, K., Leen, C., Maw, R., Mckernan, S., Mclean, L., Morris, S., Murphy, M., O'Farrell, S., Ong, E., Peters, B., Stroud, C., Wansbrough-Jones, M., Weber, J., White, D., Williams, I., Wiselka, M., Yee, T., Adams, S., Allegra, D., Andrews, L., Aneja, B., Anstead, G., Arduino, R., Artz, R., Bailowitz, J., Banks, S., Baxter, J., Baum, J., Benator, D., Black, D., Boh, D., Bonam, T., Brito, M., Brockelman, J., Bruzzese, V., Burnside, A., Cafaro, V., Casey, K., Cason, L., Childress, G., Clark, C., Clifford, D., Climo, M., Cohn, D., Couey, P., Cuervo, H., Deeks, S., Dennis, M., Diaz-Linares, M., Dickerson, D., Diez, M., Di Puppo, J., Dodson, P., Dupre, D., Elion, R., Elliott, K., El-Sadr, W., Estes, M., Fabre, J., Farrough, M., Flamm, J., Follansbee, S., Foster, C., Frank, C., Franz, J., Frechette, G., Freidland, G., Frische, J., Fuentes, L., Funk, C., Geisler, C., Genther, K., Giles, M., Goetz, M., Gonzalez, M., Graeber, C., Graziano, F., Grice, D., Hahn, B., Hamilton, C., Hassler, S., Henson, A., Hopper, S., John, M., Johnson, L., Johnson, R., Jones, R., Kahn, J., Klimas, N., Kolber, M., Koletar, S., Labriola, A., Larsen, R., Lasseter, F., Lederman, M., Ling, T., Lusch, T., Macarthur, R., Machado, C., Makohon, L., Mandelke, J., Mannheimer, S., Markowitz, N., Martinez, M., Martinez, N., Mass, M., Masur, H., Mcgregor, D., Mcintyre, D., Mckee, J., Mcmullen, D., Mettinger, M., Middleton, S., Mieras, J., Mildvan, D., Miller, P., Miller, T., Mitchell, V., Mitsuyasu, R., Moanna, A., Mogridge, C., Moran, F., Murphy, R., Mushatt, D., Nahass, R., Nixon, D., O'Brien, S., Ojeda, J., Okhuysen, P., Olson, M., Osterberger, J., Owen, W., Pablovich, S., Patel, S., Pierone, G., Poblete, R., Potter, A., Preston, E., Rappoport, C., Regevik, N., Reyelt, M., Riney, L., Rodriguez-Barradas, M., Rodriguez, J., Roland, R., Rosmarin-DeStefano, C., Rossen, W., Rouff, J., Saag, M., Santiago, S., Sarria, J., Wirtz, S., Schmidt, U., Scott, C., Sheridan, A., Shin, A., Shrader, S., Simon, G., Slowinski, D., Smith, K., Spotkov, J., Sprague, C., States, D., Suh, C., Sullivan, J., Summers, K., Sweeton, B., Tan, V., Tanner, T., Tedaldi, E., Temesgen, Z., Thomas, D., Thompson, M., Tobin, C., Toro, N., Towner, W., Upton, K., Uy, J., Valenti, S., Van Der Horst, C., Vita, J., Voell, J., Walker, J., Walton, T., Wason, K., Watson, V., Wellons, A., Weise, J., White, M., Whitman, T., Williams, B., Williams, N., Windham, J., Witt, M., Workowski, K., Wortmann, G., Wright, T., Zelasky, C., Zwickl, B., Dietz, D., Chesson, C., Vjecha, M., Schmetter, B., Grue, L., Willoughby, M., Demers, A., Dragsted, U. B., Jensen, K. B., Jansson, P. O., Jensen, B. G., Benfield, T. L., Darbyshire, J. H., Babiker, G., Fleck, S. L., Collaco-Moraes, Y., Wyzydrag, L., Drummond, F. M., Connor, S. A., Satchell, C. S., Gunn, S., Delfino, M. A., Merlin, K., Mcginley, C., Neaton, J. D., Bartsch, G., George, M., Grund, B., Hogan, C., Miller, C., Roediger, M. P., Thackeray, L., Campbell, C., Lahart, C., Perlman, D., Rein, M., Dersimonian, R., Brody, B. A., Daar, E. S., Dubler, N. N., Fleming, T. R., Freeman, D. J., Kahn, J. P., Kim, K. M., Medoff, G., Modlin, J. F., Moellering, R., Murray, B. E., Robb, M. L., Scharfstein, D. O., Sugarman, J., Tsiatis, A., Tuazon, C., Zoloth, L., Klingman, K., Lehrman, S., Belloso, W. H., Losso, M. H., Benetucci, J. A., Bogdanowicz, E. P., Cahn, P. E., Casiro, A. D., Cassetti, I., Contarelli, J. M., Corral, J. A., Crinejo, A., David, D. O., Ishida, M. T., Laplume, H. E., Lasala, M. B., Lupo, S. H., Masciottra, F., Michaan, M., Ruggieri, L., Salazar, E., Hoy, J. F., Rogers, G. D., Allworth, A. M., Anderson, J. S. C., Armishaw, J., Barnes, K., Carr, A., Chiam, A., Chuah, J. C. P., Curry, M. C., Dever, R. L., Donohue, W. A., Doong, N. C., Dwyer, D. E., Dyer, J., Eu, B., Ferguson, V. W., French, M. A. H., Garsia, R. J., Hudson, J. H., Jeganathan, S., Konecny, P., Mccormack, C. L., Mcmurchie, M., Moore, R. J., Moussa, M. B., Piper, M., Read, T., Roney, J. J., Shaw, D. R., Silvers, J., Smith, D. J., Street, A. C., Vale, R. J., Wendt, N. A., Wood, H., Youds, D. W., Zillman, J., Tozeau, V., Dewit, S., De Roo, A., Leonard, P., Lynen, L., Moutschen, M., Pereira, L. C., Souza, T. N. L., Schechter, M., Zajdenverg, R., Almeida, M. M. T. B., Araujo, F., Bahia, F., Brites, C., Caseiro, M. M., Casseb, J., Etzel, A., Falco, G. G., Filho, E. C. J., Flint, S. R., Gonzales, R., Madruga, J. V. R., Passos, L. N., Reuter, T., Sidi, L. C., Toscano, A. L. C., Cherban, E., Conway, B., Dufour, C., Foster, A., Haase, D., Haldane, H., Klein, M., Lessard, B., Martel, A., Martel, C., Paradis, E., Schlech, W., Schmidt, S., Thompson, B., Vezina, S., Reyes, M. J. W., Northland, R., Ostergaard, L., Hergens, L., Loftheim, I. R., Raukas, M., Zilmer, K., Justinen, J., Ristola, M., Landman, R., Abel, S., Abgrall, S., Amat, K., Auperin, L., Barruet, R., Benalycherif, A., Benammar, N., Bentata, M., Besnier, J. M., Blanc, M., Cabie, A., Chavannet, P., Dargere, S., De La Tribonniere, X., Debord, T., Decaux, N., Delgado, J., Dupon, M., Durant, J., Frixon-Marin, V., Genet, C., Gerard, L., Gilquin, J., Jeantils, V., Kouadio, H., Leclercq, P., Lelievre, J. D., Michon, C. P., Nau, P., Pacanowski, J., Piketty, C., Salmon, D., Schmit, J. L., Serini, M. A., Tassi, S., Touam, F., Verdon, R., Weinbreck, P., Yazdanpanah, Y., Yeni, P., Fatkenheuer, G., Bitsch, S., Bogner, J. R., Goebel, F. D., Lehmann, C., Lennemann, T., Wasmuth, J. C., Wiedemeyer, K., Hatzakis, A., Touloumi, G., Antoniadou, A., Daikos, G. L., Dimitrakaki, A., Gargalianos-Kakolyris, P., Giannaris, M., Karafoulidou, A., Katsambas, A., Katsarou, O., Kontos, A. N., Kordossis, T., Lazanas, M. K., Panagopoulos, P., Panos, G., Paparizos, V., Papastamopoulos, V., Petrikkos, G., Sambatakou, H., Skoutelis, A., Tsogas, N., Xylomenos, G., Bergin, C. J., Mooka, B., Mamorksy, M. G., Agmon-Levin, N., Karplus, R., Maayan, S., Shahar, E., Turner, D., Abeli, C., Biglino, A., Bonora, S., De Gioanni, M., Di Perri, G., Montroni, M., Quirino, T., Raise, E., Honda, M., Ishisaka, M., Caplinskas, S., Uzdaviniene, V., Schmit, J. C., Staub, T., Mills, G. D., Blackmore, T., Masters, J. A., Morgan, J., Pithie, A., Brunn, J., Ormassen, V., La Rosa, A., Guerra, O., Espichan, M., Gutierrez, L., Mendo, F., Salazar, R., Knytz, B., Kwiatkowski, J., Castro, R. S., Horta, A., Miranda, A. C., Pinto, I. V., Vera, J., Rakhmanova, A., Vinogradova, E., Yakovlev, A., Zakharova, N., Wood, R., Orrel, C., Arnaiz, J. A., Carrillo, R., Dalmau, D., Jordano, Q., Knobel, H., Larrousse, M., Moreno, J. S., Oretaga, E., Pena, J. N., Hirschel, B., Spycher, R., Battegay, M., Bottone, S., Cavassini, M., Christen, A., Furrer, H. J., Gayet-Ageron, A., Genne, D., Hochstrasser, S., Moens, C., Muller, N., Nuesch, R., Ruxrungtham, K., Pumpradit, W., Dangthongdee, S., Kiertiburanakul, S., Klinbuayaem, V., Mootsikapun, P., Nonenoy, S., Piyavong, B., Prasithsirikul, W., Raksakulkarn, P., Gazzard, B. G., Ainsworth, J. G., Angus, B. J., Barber, T. J., Brook, M. G., Care, C. D., Chadwick, D. R., Chikohora, M., Churchill, D. R., Cornforth, D., Dockrell, D. H., Easterbrook, P. J., Fox, P. A., Gomez, P. A., Gompels, M. M., Harris, G. M., Herman, S., Jackson, A. G. A., Jebakumar, S. P. R., Kinghorn, G. R., Kuldanek, K. A., Larbalestier, N., Lumsden, M., Maher, T., Mantell, J., Muromba, L., Orkin, C. M., Peters, S., Peto, T. E. A., Portsmouth, S. D., Rajamanoharan, S., Ronan, Schwenk, A., Slinn, M. A., Stroud, C. J., Thomas, R. C., Wansbrough-Jones, M. H., Whiles, H. J., White, D. J., Williams, E., Williams, G., Youle, M., Abrams, D. I., Acosta, E. A., Adamski, A., Antoniskis, D., Aragon, D. R., Barnett, B. J., Baroni, C., Barron, M., Baxter, J. D., Beers, D., Beilke, M., Bemenderfer, Bernard, A., Besch, C. L., Bessesen, M. T., Bethel, J. T., Blue, S., Blum, J. D., Boarden, S., Bolan, R. K., Borgman, J. B., Brar, I., Braxton, B. K., Bredeek, U. F., Brennan, R., Britt, D. E., Bulgin-Coleman, D., Bullock, E., Campbell, B., Caras, S., Carroll, J., Casey, K. K., Chiang, F., Cindrich, R. B., Cohen, C., Coley, J., Condoluci, D. V., Contreras, R., Corser, J., Cozzolino, J., Crane, L. R., Daley, L., Dandridge, D., D'Antuono, V., Darcourt Rizo Patron, J. G., Dehovitz, J. A., Dejesus, E., Desjardin, J., Dietrich, C., Dolce, A., Erickson, D., Faber, L. L., Falbo, J., Farrough, M. J., Farthing, C. F., Ferrell-Gonzalez, P., Flynn, H., Frank, M., Freeman, K. F., French, N., Friedland, G., Fujita, N., Gahagan, L., Gilson, I., Goetz, M. B., Goodwin, E., Guity, C. K., Gulick, P., Gunderson, E. R., Hale, C. M., Hannah, K., Henderson, H., Hennessey, K., Henry, W. K., Higgins, T., Hodder, S. L., Horowitz, H. W., Howe-Pittman, M., Hubbard, J., Hudson, R., Hunter, H., Hutelmyer, C., Insignares, M. T., Jackson, L., Jenny, L., Johnson, D. L., Johnson, G., Johnson, J., Kaatz, J., Kaczmarski, J., Kagan, S., Kantor, C., Kempner, T., Kieckhaus, K., Kimmel, N., Klaus, B. M., Koeppe, J. R., Koirala, J., Kopka, J., Kostman, J. R., Kozal, M. J., Kumar, A., Lampiris, H., Lamprecht, C., Lattanzi, K. M., Lee, J., Leggett, J., Long, C., Loquere, A., Loveless, K., Lucasti, C. J., Luskin-Hawk, R., Macveigh, M., Makohon, L. H., Markowitz, N. P., Marks, C., Martorell, C., Mcfeaters, E., Mcgee, B., Mcintyre, D. M., Mcmanus, E., Melecio, L. G., Melton, D., Mercado, S., Merrifield, E., Mieras, J. A., Mogyoros, M., Moran, F. M., Murphy, K., Mutic, S., Nadeem, I., Nadler, J. P., Ognjan, A., O'Hearn, M., O'Keefe, K., Okhuysen, P. C., Oldfield, E., Olson, D., Orenstein, R., Ortiz, R., Parpart, F., Pastore-Lange, V., Paul, S., Pavlatos, A., Pearce, D. D., Pelz, R., Peterson, S., Pitrak, D., Powers, S. L., Pujet, H. C., Raaum, J. W., Ravishankar, J., Reeder, J., Reilly, N. A., Reyelt, C., Riddell, J., Rimland, D., Robinson, M. L., Rodriguez, A. E., Rodriguez Derouen, V., Rosmarin, C., Rossen, W. L., Rouff, J. R., Sands, M., Savini, C., Schrader, S., Schulte, M. M., Scott, R., Seedhom, H., Sension, M., Sheblehall, A., Shuter, J., Slater, L. N., Slotten, R., Smith, M., Snap, S., States, D. M., Stringer, G., Summers, K. K., Swanson, K., Sweeton, I. B., Szabo, S., Tedaldi, E. M., Telzak, E. E., Thompson, M. A., Thompson, S., Bong, C. T. H., Vaccaro, A., Vasco, L. M., Vecino, I., Verlinghieri, G. K., Visnegarwala, F., Wade, H., Weis, S. E., Weise, J. A., Weissman, S., Wilkin, M., Witter, J. H., Wojtusic, L., Wright, T. J., Yeh, V., Young, B., Zeana, C., Zeh, J., Savio, E., Vacarezza, M., and Pacheco, Antonio Guilherme
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Adult ,CD4-Positive T-Lymphocytes ,Male ,General Science & Technology ,Anti-HIV Agents ,T cell ,lcsh:Medicine ,Antiretroviral Therapy ,HIV Infections ,Biology ,Essential hypertension ,Logistic regression ,Malignancy ,Acquired immunodeficiency syndrome (AIDS) ,Clinical Research ,Antiretroviral Therapy, Highly Active ,microRNA ,medicine ,Genetics ,2.1 Biological and endogenous factors ,Humans ,Highly Active ,Aetiology ,lcsh:Science ,Genetic Association Studies ,Multidisciplinary ,lcsh:R ,Case-control study ,Middle Aged ,medicine.disease ,3. Good health ,Circulating MicroRNA ,MicroRNAs ,medicine.anatomical_structure ,Infectious Diseases ,Good Health and Well Being ,INSIGHT ESPRIT and SMART Study Groups ,Immunology ,HIV-1 ,HIV/AIDS ,lcsh:Q ,Female ,Infection ,Biomarkers ,Biotechnology ,Research Article - Abstract
Introduction The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR-145 correlated with nadir CD4+ T cell count. Discussion No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection.
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- 2015
257. Development and validation of a risk score for chronic kidney disease in HIV infection using prospective cohort data from the D:A:D study
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Mocroft, Amanda, Lundgren, Jens D., Ross, Michael, Law, Matthew, Reiss, Peter, Kirk, Ole, Smith, Colette, Wentworth, Deborah, Neuhaus, Jacqueline, Fux, Christoph A., Moranne, Olivier, Morlat, Phillipe, Johnson, Margaret A., Ryom, Lene, Lundgren, J. D., Powderly, B., Shortman, N., Moecklinghoff, C., Reilly, G., Franquet, X., Sabin, C. A., Phillips, A., Kirk, O., Reiss, P., Weber, R., Pradier, C., Law, M., d'Arminio Monforte, A., Dabis, F., El-Sadr, W. M., De Wit, S., Ryom, L., Kamara, D., Smith, C., Mocroft, A., Tverland, J., Mansfeld, M., Nielsen, J., Raben, D., Salbøl Brandt, R., Rickenbach, M., Fanti, I., Krum, E., Hillebregt, M., Geffard, S., Sundström, A., Delforge, M., Fontas, E., Torres, F., Mcmanus, H., Wright, S., Kjær, J., Sjøl, A., Meidahl, P., Helweg-Larsen, J., Schmidt Iversen, J., Ross, M., Fux, C. A., Morlat, P., Moranne, O., Kesselring, A. M., Kamara, D. A., Friis-Møller, N., Kowalska, J., Sabin, C., Bruyand, M., Bower, M., Fätkenheuer, G., Donald, A., Grulich, A., Prins, J. M., Kuijpers, T. W., Scherpbier, H. J., van der Meer, J. T. M., Wit, F. W. M. N., Godfried, M. H., van der Poll, T., Nellen, F. J. B., Geerlings, S. E., van Vugt, M., Pajkrt, D., Bos, J. C., Wiersinga, W. J., van der Valk, M., Goorhuis, A., Hovius, J. W., van Eden, J., Henderiks, A., van Hes, A. M. H., Mutschelknauss, M., Nobel, H. E., Pijnappel, F. J. J., Westerman, A. M., Jurriaans, S., Back, N. K. T., Zaaijer, H. L., Berkhout, B., Cornelissen, M. T. E., Schinkel, C. J., Thomas, X. V., van den Berge, M., Stegeman, A., Baas, S., Hage de Looff, L., Versteeg, D., Pronk, M. J. H., Ammerlaan, H. S. M., Korsten-Vorstermans, E. M. H. M., de Munnik, E. S., Jansz, A. R., Tjhie, J., Wegdam, M. C. A., Deiman, B., Scharnhorst, V., van der Plas, A., Weijsenfeld, A. M., van der Ende, M. E., de Vries-Sluijs, T. E. M. S., C. M. van Gorp, E., Schurink, C. A. M., Nouwen, J. 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B., Jensen, K. B., Jansson, P. O., Jensen, B. G., Benfield, T. L., Darbyshire, J. H., Babiker, A. G., Palfreeman, A. J., Fleck, S. L., Collaco-Moraes, Y., Wyzydrag, L., Cooper, D. A., Drummond, F. M., Connor, S. A., Satchell, C. S., Gunn, S., Delfino, M. A., Merlin, K., Mcginley, C., Neaton, J. D., George, M., Grund, B., Hogan, C., Miller, C., Neuhaus, J., Roediger, M. P., Thackeray, L., Campbell, C., Lahart, C., Perlman, D., Rein, M., Dersimonian, R., Brody, B. A., Daar, E. S., Dubler, N. N., Fleming, T. R., Freeman, D. J., Kahn, J. P., Kim, K. M., Medoff, G., Modlin, J. F., Moellering, R., Murray, B. E., Robb, M. L., Scharfstein, D. O., Sugarman, J., Tsiatis, A., Tuazon, C., Zoloth, L., Belloso, W. H., Losso, M. H., Benetucci, J. A., Bogdanowicz, E. P., Cahn, P. E., Casiró, A. D., Cassetti, I., Contarelli, J. M., Corral, J. A., Crinejo, A., David, D. O., Ishida, M. T., Laplume, H. E., Lasala, M. B., Lupo, S. H., Masciottra, F., Michaan, M., Ruggieri, L., Salazar, E., Sánchez, M., Hoy, J. F., Rogers, G. D., Allworth, A. M., Anderson, J. S. C., Armishaw, J., Barnes, K., Chiam, A., Chuah, J. C. P., Curry, M. C., Dever, R. L., Donohue, W. A., Doong, N. C., Dwyer, D. E., Dyer, J., Eu, B., Ferguson, V. W., French, M. A. H., Garsia, R. J., Hudson, J. H., Jeganathan, S., Konecny, P., Mccormack, C. L., Mcmurchie, M., Moore, R. J., Moussa, M. B., Piper, M., Read, T., Roney, J. J., Shaw, D. R., Silvers, J., Smith, D. J., Street, A. C., Vale, R. J., Wendt, N. A., Wood, H., Youds, D. W., Zillman, J., Tozeau, V., de Roo, A., Leonard, P., Lynen, L., Moutschen, M., Pereira, L. C., Souza, T. N. L., Schechter, M., Zajdenverg, R., Almeida, M. M. T. B., Araujo, F., Bahia, F., Brites, C., Caseiro, M. M., Casseb, J., Etzel, A., Falco, G. G., Filho, E. C. J., Flint, S. R., Gonzales, C. R., Madruga, J. V. R., Passos, L. N., Reuter, T., Sidi, L. C., Toscano, A. L. C., Cherban, E., Conway, B., Dufour, C., Foster, A., Haase, D., Haldane, H., Klein, M., Lessard, B., Martel, A., Martel, C., Paradis, E., Schlech, W., Schmidt, S., Thompson, B., Vezina, S., Wolff Reyes, M. J., Northland, R., Hergens, L., Loftheim, I. R., Raukas, M., Justinen, J., Landman, R., Abel, S., Abgrall, S., Amat, K., Auperin, L., Barruet, R., Benalycherif, A., Benammar, N., Bentata, M., Besnier, J. M., Blanc, M., Cabié, A., Chavannet, P., Dargere, S., de la Tribonniere, X., Debord, T., Decaux, N., Delgado, J., Frixon-Marin, V., Genet, C., Gérard, L., Gilquin, J., Jeantils, V., Kouadio, H., Leclercq, P., Lelièvre, J. -D., Levy, Y., Michon, C. P., Nau, P., Pacanowski, J., Piketty, C., Salmon, D., Schmit, J. L., Serini, M. A., Tassi, S., Touam, F., Verdon, R., Weinbreck, P., Yazdanpanah, Y., Yeni, P., Bitsch, S., Bogner, J. R., Goebel, F. D., Lehmann, C., Lennemann, T., Potthof, A., Wasmuth, J. C., Wiedemeyer, K., Hatzakis, A., Touloumi, G., Antoniadou, A., Daikos, G. L., Dimitrakaki, A., Gargalianos-Kakolyris, P., Giannaris, M., Karafoulidou, A., Katsambas, A., Katsarou, O., Kontos, A. N., Kordossis, T., Lazanas, M. K., Panagopoulos, P., Paparizos, V., Papastamopoulos, V., Petrikkos, G., Skoutelis, A., Tsogas, N., Bergin, C. J., Mooka, B., Mamorksy, M. G., Agmon-Levin, N., Karplus, R., Shahar, E., Biglino, A., De Gioanni, M., Montroni, M., Raise, E., Honda, M., Ishisaka, M., Caplinskas, S., Uzdaviniene, V., Schmit, J. C., Mills, G. D., Blackmore, T., Masters, J. A., Morgan, J., Pithie, A., Brunn, J., Ormasssen, V., La Rosa, A., Guerra, O., Espichan, M., Gutierrez, L., Mendo, F., Salazar, R., Knytz, B., Kwiatkowski, J., Castro, R. S., Horta, A., Miranda, A. C., Pinto, I. V., Vera, J., Vinogradova, E., Yakovlev, A., Wood, R., Orrel, C., Arnaiz, J. A., Carrillo, R., Dalmau, D., Jordano, Q., Knobel, H., Larrousse, M., Moreno, J. S., Oretaga, E., Pena, J. N., Spycher, R., Bottone, S., Christen, A., Franc, C., Furrer, H. J., Gayet-Ageron, A., Genné, D., Hochstrasser, S., Moens, C., Nüesch, R., Ruxrungtham, K., Pumpradit, W., Dangthongdee, S., Kiertiburanakul, S., Klinbuayaem, V., Mootsikapun, P., Nonenoy, S., Piyavong, B., Prasithsirikul, W., Raksakulkarn, P., Gazzard, B. G., Ainsworth, J. G., Angus, B. J., Barber, T. J., Brook, M. G., Care, C. D., Chadwick, D. R., Chikohora, M., Churchill, D. R., Cornforth, D., Dockrell, D. H., Easterbrook, P. J., Fox, P. A., Gomez, P. A., Gompels, M. M., Harris, G. M., Herman, S., Jackson, A. G. A., Jebakumar, S. P. R., Kinghorn, G. R., Kuldanek, K. A., Larbalestier, N., Lumsden, M., Maher, T., Mantell, J., Muromba, L., Orkin, C. M., Peters, B. S., Peto, T. E. A., Portsmouth, S. D., Rajamanoharan, S., Ronan, A., Schwenk, A., Slinn, M. A., Stroud, C. J., Thomas, R. C., Wansbrough-Jones, M. H., Whiles, H. J., White, D. J., Williams, E., Williams, I. G., Acosta, E. A., Adamski, A., Antoniskis, D., Aragon, D. R., Barnett, B. J., Baroni, C., Barron, M., Baxter, J. D., Beers, D., Beilke, M., Bemenderfer, D., Bernard, A., Besch, C. L., Bessesen, M. T., Bethel, J. T., Blue, S., Blum, J. D., Boarden, S., Bolan, R. K., Borgman, J. B., Brar, I., Braxton, B. K., Bredeek, U. F., Brennan, R., Britt, D. E., Bulgin-Coleman, D., Bullock, D. E., Campbell, B., Caras, S., Carroll, J., Casey, K. K., Chiang, F., Cindrich, R. B., Clark, C., Cohen, C., Coley, J., Condoluci, D. V., Contreras, R., Corser, J., Cozzolino, J., Daley, L., Dandridge, D., D'Antuono, V., Darcourt Rizo Patron, J. G., Dehovitz, J. A., Dejesus, E., Desjardin, J., Dietrich, C., Dolce, E., Erickson, D., Faber, L. L., Falbo, J., Farrough, M. J., Farthing, C. F., Ferrell-Gonzalez, P., Flynn, H., Frank, M., Freeman, K. F., French, N., Fujita, N., Gahagan, L., Gilson, I., Goetz, M. B., Goodwin, E., Guity, C. K., Gulick, P., Gunderson, E. R., Hale, C. M., Hannah, K., Henderson, H., Hennessey, K., Henry, W. K., Higgins, D. T., Hodder, S. L., Horowitz, H. W., Howe-Pittman, M., Hubbard, J., Hudson, R., Hunter, H., Hutelmyer, C., Insignares, M. T., Jackson, L., Jenny, L., Johnson, D. L., Johnson, G., Johnson, J., Kaatz, J., Kaczmarski, J., Kagan, S., Kantor, C., Kempner, T., Kieckhaus, K., Kimmel, N., Klaus, B. M., Koeppe, J. R., Koirala, J., Kopka, J., Kostman, J. R., Kozal, M. J., Kumar, A., Lampiris, H., Lamprecht, C., Lattanzi, K. M., Lee, J., Leggett, J., Long, C., Loquere, A., Loveless, K., Lucasti, C. J., Macveigh, M., Makohon, L. H., Markowitz, N. P., Marks, C., Martorell, C., Mcfeaters, E., Mcgee, B., Mcintyre, D. M., Mcmanus, E., Melecio, L. G., Melton, D., Mercado, S., Merrifield, E., Mieras, J. A., Mogyoros, M., Moran, F. M., Murphy, K., Mutic, S., Nadeem, I., Nadler, J. P., Ognjan, A., O'Hearn, M., O'Keefe, K., Okhuysen, P. C., Oldfield, E., Olson, D., Orenstein, R., Ortiz, R., Parpart, F., Pastore-Lange, V., Paul, S., Pavlatos, A., Pearce, D. D., Pelz, R., Peterson, S., Pitrak, D., Powers, S. L., Pujet, H. C., Raaum, J. W., Ravishankar, J., Reeder, J., Reilly, N. A., Reyelt, C., Riddell, J., Rimland, D., Robinson, M. L., Rodriguez, A. E., Rodriguez-Barradas, M. C., Rodriguez Derouen, V., Rosmarin, C., Rossen, W. L., Rouff, J. R., Sampson, J. H., Sands, M., Savini, C., Schrader, S., Schulte, M. M., Scott, R., Seedhom, H., Sension, M., Sheble-Hall, A., Shuter, J., Slater, L. N., Slotten, R., Smith, M., Snap, S., States, D. M., Stringer, G., Summers, K. K., Swanson, K., Sweeton, I. B., Szabo, S., Tedaldi, E. M., Telzak, E. E., Thompson, M. A., Thompson, S., Ting Hong Bong, C., Vaccaro, A., Vasco, L. M., Vecino, I., Verlinghieri, G. K., Visnegarwala, F., Wade, B. H., Weis, S. E., Weise, J. A., Weissman, S., Wilkin, A. M., Witter, J. H., Wojtusic, L., Wright, T. J., Yeh, V., Young, B., Zeana, C., Zeh, J., Savio, E., Vacarezza, M., University College of London [London] (UCL), University of Copenhagen = Københavns Universitet (KU), University of New South Wales [Sydney] (UNSW), University of Amsterdam [Amsterdam] (UvA), University of Minnesota [Twin Cities] (UMN), University of Minnesota System, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nice (CHU Nice), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Med Microbiol, Infect Dis & Infect Prev, RS: NUTRIM - R3 - Chronic inflammatory disease and wasting, RS: CAPHRI School for Public Health and Primary Care, RS: CAPHRI - R4 - Health Inequities and Societal Participation, Interne Geneeskunde, Chemical Biology, Mocroft, A, Lundgren, J, Ross, M, Law, M, Reiss, P, Kirk, O, Smith, C, Wentworth, D, Neuhaus, J, Fux, C, Moranne, O, Morlat, P, Johnson, M, Ryom, L, Gori, A, Internal medicine, CCA - Innovative therapy, ICaR - Circulation and metabolism, Medical Microbiology and Infection Prevention, CCA - Disease profiling, CCA - Immuno-pathogenesis, Plastic, Reconstructive and Hand Surgery, Mocroft, Amanda, Lundgren, Jens D., Ross, Michael, Law, Matthew, Reiss, Peter, Kirk, Ole, Smith, Colette, Wentworth, Deborah, Neuhaus, Jacqueline, Fux, Christoph A., Moranne, Olivier, Morlat, Phillipe, Johnson, Margaret A., Ryom, Lene, D:a:d Study, Group, Castagna, Antonella, the Royal Free Hospital Clinic, Cohort, and the, Insight, Smart, and ESPRIT, Study, Clinicum, Department of Medicine, Herrada, Anthony, University of Copenhagen = Københavns Universitet (UCPH), AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, Global Health, Other departments, Infectious diseases, Paediatric Infectious Diseases / Rheumatology / Immunology, General Internal Medicine, Center of Experimental and Molecular Medicine, Graduate School, Gastroenterology and Hepatology, Dermatology, ACS - Amsterdam Cardiovascular Sciences, Other Research, Anesthesiology, and Bartlett, John
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Male ,Adult ,Age Factors ,Anti-HIV Agents ,CD4 Lymphocyte Count ,Clinical Decision-Making ,Comorbidity ,Female ,HIV ,HIV Infections ,HIV Seropositivity ,Humans ,Incidence ,Kidney ,Middle Aged ,Prospective Studies ,Renal Insufficiency, Chronic ,Risk ,Risk Assessment ,Sex Factors ,urologic and male genital diseases ,Biochemistry ,0302 clinical medicine ,ANTIRETROVIRAL THERAPY ,Adult, Age Factors, Anti-HIV Agents, CD4 Lymphocyte Count, Clinical Decision-Making, Comorbidity, Female, HIV, HIV Infections, HIV Seropositivity, Humans, Incidence, Kidney, Male, Middle Aged, Prospective Studies, Renal Insufficiency, Chronic, Risk, Risk Assessment, Sex Factors ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Age Factor ,Chronic ,STAGE RENAL-DISEASE ,PROTEINURIA ,virus diseases ,11 Medical And Health Sciences ,General Medicine ,ASSOCIATION ,6. Clean water ,female genital diseases and pregnancy complications ,3. Good health ,HIV/AIDS ,Medicine ,Infection ,psychological phenomena and processes ,Human ,medicine.medical_specialty ,Renal function ,NEFROPATIAS ,chronic kidney disease ,risk score model ,12. Responsible consumption ,ESPRIT study group ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Clinical Research ,D:A:D study group ,Intensive care medicine ,medicine (all) ,Molecular Biology ,Royal Free Hospital Clinic Cohort ,Prevention ,Anti-HIV Agent ,medicine.disease ,Prospective Studie ,lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] ,Immunology ,Kidney Disease ,PREDICTION ,POSITIVE PERSONS ,030232 urology & nephrology ,Sex Factor ,SDG 3 – Goede gezondheid en welzijn ,Medical and Health Sciences ,GLOMERULAR-FILTRATION-RATE ,[SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology ,INSIGHT study group ,HIV Infection ,LIFE EXPECTANCY ,030212 general & internal medicine ,Renal Insufficiency ,Prospective cohort study ,Framingham Risk Score ,Incidence (epidemiology) ,adult ,age factors ,anti-hiv agents ,CD4 lymphocyte count ,clinical decision-making ,comorbidity ,female ,hiv ,hiv infections ,hiv seropositivity ,humans ,incidence ,kidney ,male ,middle aged ,prospective studies ,renal insufficiency, chronic ,risk ,risk assessment ,sex factors ,SMART study group ,6.1 Pharmaceuticals ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Patient Safety ,Risk assessment ,Biotechnology ,Research Article ,Settore MED/17 - MALATTIE INFETTIVE ,NO ,A:D study group [D] ,General & Internal Medicine ,Diabetes mellitus ,mental disorders ,medicine ,EXPOSURE ,business.industry ,Evaluation of treatments and therapeutic interventions ,Cell Biology ,[SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology ,INDIVIDUALS ,Good Health and Well Being ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,3121 General medicine, internal medicine and other clinical medicine ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,business ,Kidney disease - Abstract
Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with ≥3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR ≤ 60 ml/min/1.73 m2. Poisson regression was used to develop a risk score, externally validated on two independent cohorts. In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7–6.7; median follow-up 6.1 y, range 0.3–9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was −2 (interquartile range –4 to 2). There was a 1:393 chance of developing CKD in the next 5 y in the low risk group (risk score < 0, 33 events), rising to 1:47 and 1:6 in the medium (risk score 0–4, 103 events) and high risk groups (risk score ≥ 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166–3,367); NNTH was 202 (95% CI 159–278) and 21 (95% CI 19–23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506–1462), 88 (95% CI 69–121), and 9 (95% CI 8–10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3–12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6–8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD., Editors’ Summary Background About 35 million people are currently infected with HIV, the virus that causes AIDS. HIV destroys CD4 lymphocytes and other immune system cells, leaving infected individuals susceptible to other infections. HIV infection can be controlled, but not cured, using combination antiretroviral therapy (cART), and, nowadays, the life expectancy of many HIV-positive individuals is similar to that of HIV-negative people. HIV-positive individuals nevertheless experience some illnesses more frequently than HIV-negative people do. For example, up to a third of HIV-positive individuals develop chronic kidney disease (CKD), which is associated with an increased risk of cardiovascular disease and death. Persons with CKD may have an impaired effect of the filtration units in the kidneys that remove waste products and excess water from the blood to make urine, thereby leading to a reduced blood filtration rate (the estimated glomerular filtration rate [eGFR]) and waste product accumulation in the blood. Symptoms of CKD, which rarely occur until the disease is advanced, include tiredness, swollen feet, and frequent urination. Advanced stages of CKD cannot be cured, but its progression can be slowed by, for example, controlling hypertension (high blood pressure) and diabetes (two CDK risk factors) and by adopting a healthy lifestyle. Why Was This Study Done? The burden of CKD may increase among HIV-positive individuals as they age, and clinicians need to know which individuals are at high risk of developing CKD when choosing cART regimens for their patients. In addition, clinicians need to be able to identify those HIV-positive individuals at greatest risk of CKD so that they can monitor them for early signs of kidney disease. Some antiretroviral drugs—for example, tenofovir and atazanavir/ritonavir (a boosted protease inhibitor)—are associated with kidney damage. Clinicians may need to weigh the benefits and risks of giving such potentially nephrotoxic drugs to individuals who already have a high CKD risk. Here, the researchers develop and validate a simple, widely applicable risk score (a risk prediction model) for CKD among HIV-positive individuals and investigate the relationship between CKD and potentially nephrotoxic antiretroviral drugs among individuals with different CKD risk score profiles. What Did the Researchers Do and Find? To develop their CKD risk score, the researchers used clinical and demographic data collected from 17,954 HIV-positive individuals enrolled in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study who had an eGFR > 60 ml/min/1.73 m2 and were not taking a potentially nephrotoxic antiretroviral at baseline. During 103,185 person-years of follow-up, 641 individuals developed CKD. Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease predicted CKD. The researchers included these nine factors in their risk score model (which is available online) and defined three risk groups: low (risk score < 0), medium (risk score 0–4), and high (risk score ≥ 5) risk of CKD development in the next five years. Specifically, there was a 1 in 393, 1 in 47, and 1 in 6 chance of developing CKD in the next five years in the low, medium, and high risk groups, respectively. Because some patients started to use potentially nephrotoxic antiretroviral drugs during follow-up, the researchers were able to use their risk score model to calculate how many patients would have to be treated with one of these drugs for an additional patient to develop CKD over five years in each risk group. This “number needed to harm” (NNTH) for patients starting treatment with tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor was 739, 88, and 9 in the low, medium, and high risk groups, respectively. Finally, the researchers validated the accuracy of their risk score in two independent HIV study groups. What Do These Findings Mean? These findings provide a simple, validated risk score for CKD and indicate that the NNTH when starting potentially nephrotoxic antiretrovirals was low among HIV-positive individuals at the highest risk of CKD (i.e., treating just nine individuals with nephrotoxic antiretroviral drugs will likely lead to an additional case of CKD in five years). Although various aspects of the study, including the lack of data on race, limit the accuracy of these findings, these findings highlight the need for monitoring, screening, and chronic disease prevention to minimize the risk of HIV-positive individuals developing diabetes, hypertension, or cardiovascular disease, or becoming coinfected with hepatitis C, all of which contribute to the CKD risk score. Moreover, the development of a tool for estimating an individual’s five-year risk of developing CKD with or without the addition of potentially nephrotoxic antiretroviral drugs will enable clinicians and patients to weigh the benefits of certain antiretroviral drugs against the risk of CKD and make informed decisions about treatment options. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001809. Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and personal stories about living with AIDS/HIV Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including personal stories about living with HIV/AIDS The World Health Organization provides information on all aspects of HIV/AIDS (in several languages), including its guidelines on the use of ART for treating and preventing HIV infection The UNAIDS World AIDS Day Report 2014 provides up-to-date information about the AIDS epidemic and efforts to halt it The UK National Health Service Choices website provides information for patients on chronic kidney disease, including some personal stories The US National Kidney Foundation, a not-for-profit organization, provides information about chronic kidney disease (in English and Spanish) A tool for calculating the CDK risk score developed in this study is available Additional information about the D:A:D study is available, Amanda Mocroft and colleagues develop and validate a model for determining risk of developing chronic kidney disease for individuals with HIV if treated with different antiretroviral therapies.
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- 2015
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258. Prognostic significance of the estrogen-regulated protein, cathepsin D, in breast cancer: an immunohistochemical study
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Henry, J.A., McCarthy, Anne L., Angus, B., Westley, B.R., May, Felicity E.B., Nicholson, S., Cairns, J., Harris, A.L., and Horne, C.H.W.
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Breast cancer -- Prognosis ,Health - Abstract
Breast cancers are sensitive to the hormone estrogen, and many therapeutic regimens take this fact into account. There is much research interest in elucidating the effect that estrogen has on breast cancer cells, and some of this research has identified cathepsin D as a protein which the cells synthesize in greater quantity when stimulated by estrogen. Cathepsin D is a lysosomal protease, which means it is an enzyme that works to digest other proteins within the lysosome, a recycling location where aging and nonfunctional proteins are dissolved and their component parts are returned to the cell for further use. To determine whether cathepsin D may have clinical significance, tissue specimens from 94 cases of operable breast cancer were examined. Staining of the specimens with antibodies to cathepsin D revealed its presence in 62 of 94 patients. There was no significant difference in cathepsin D staining which could be attributed to patient age or menopausal status. Considered overall, staining for cathepsin D was not significantly associated with increased survival time, but when patients whose cells expressed the estrogen receptor were considered separately, the presence of cathepsin D was prognostic for increased survival. The presence of cathepsin D was unrelated to survival among patients without the estrogen receptor on their cancer cells. Cathepsin D was also associated with increased survival among patients with metastases to the lymph nodes. The reason for the association of cathepsin D with improved prognosis is difficult to explain, especially considering that cathepsin D is thought to aid metastatic cells in the invasion of tissues. It may be that the expression of cathepsin D in these tissues is a marker for estrogen receptor function. Further studies should examine the relationship of cathepsin D to the endocrine response, and evaluate it in relation to other tumor markers and prognostic factors. (Consumer Summary produced by Reliance Medical Information, Inc.)
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- 1990
259. C9ORF72 repeat expansion causes vulnerability of motor neurons to Ca2+-permeable AMPA receptor-mediated excitotoxicity
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Selvaraj, Bhuvaneish T., primary, Livesey, Matthew R., additional, Zhao, Chen, additional, Gregory, Jenna M., additional, James, Owain T., additional, Cleary, Elaine M., additional, Chouhan, Amit K., additional, Gane, Angus B., additional, Perkins, Emma M., additional, Dando, Owen, additional, Lillico, Simon G., additional, Lee, Youn-Bok, additional, Nishimura, Agnes L., additional, Poreci, Urjana, additional, Thankamony, Sai, additional, Pray, Meryll, additional, Vasistha, Navneet A., additional, Magnani, Dario, additional, Borooah, Shyamanga, additional, Burr, Karen, additional, Story, David, additional, McCampbell, Alexander, additional, Shaw, Christopher E., additional, Kind, Peter C., additional, Aitman, Timothy J., additional, Whitelaw, C. Bruce A., additional, Wilmut, Ian, additional, Smith, Colin, additional, Miles, Gareth B., additional, Hardingham, Giles E., additional, Wyllie, David J. A., additional, and Chandran, Siddharthan, additional
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- 2018
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260. Copper selects for siderophore-mediated virulence in Pseudomonas aeruginosa
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Luke Lear, Elze Hesse, Angus Buckling, and Michiel Vos
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Evolution of virulence ,Opportunistic pathogen ,Metal detoxification ,Pyoverdine ,Coincidental selection ,Microbiology ,QR1-502 - Abstract
Abstract Background Iron is essential for almost all bacterial pathogens and consequently it is actively withheld by their hosts. However, the production of extracellular siderophores enables iron sequestration by pathogens, increasing their virulence. Another function of siderophores is extracellular detoxification of non-ferrous metals. Here, we experimentally link the detoxification and virulence roles of siderophores by testing whether the opportunistic pathogen Pseudomonas aeruginosa displays greater virulence after exposure to copper. To do this, we incubated P. aeruginosa under different environmentally relevant copper regimes for either two or twelve days. Subsequent growth in a copper-free environment removed phenotypic effects, before we quantified pyoverdine production (the primary siderophore produced by P. aeruginosa), and virulence using the Galleria mellonella infection model. Results Copper selected for increased pyoverdine production, which was positively correlated with virulence. This effect increased with time, such that populations incubated with high copper for twelve days were the most virulent. Replication of the experiment with a non-pyoverdine producing strain of P. aeruginosa demonstrated that pyoverdine production was largely responsible for the change in virulence. Conclusions We here show a direct link between metal stress and bacterial virulence, highlighting another dimension of the detrimental effects of metal pollution on human health.
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- 2022
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261. Evaluation of the immunogenicity and impact on the latent HIV-1 reservoir of a conserved region vaccine, MVA.HIVconsv, in antiretroviral therapy-treated subjects
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Hancock, G, Morón-López, S, Kopycinski, J, Puertas, MC, Giannoulatou, E, Rose, A, Salgado, M, Hayton, EJ, Crook, A, Morgan, C, Angus, B, Chen, F, Yang, H, Martinez-Picado, J, Hanke, T, Dorrell, L, Hancock, G, Morón-López, S, Kopycinski, J, Puertas, MC, Giannoulatou, E, Rose, A, Salgado, M, Hayton, EJ, Crook, A, Morgan, C, Angus, B, Chen, F, Yang, H, Martinez-Picado, J, Hanke, T, and Dorrell, L
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© 2017 Hancock G et al; licensee International AIDS Society. Introduction: Vaccines may be key components of a curative strategy for HIV-1. We investigated whether a novel immunogen, HIVconsv, designed to re-direct T cell responses to conserved viral epitopes, could impact the HIV-1 reservoir in chronic antiretroviral therapy (ART)-treated subjects when delivered by modified vaccinia virus Ankara (MVA). Methods: Nineteen virologically suppressed individuals were randomized to receive vaccinations with MVA.HIVconsv (5.5 × 107plaque-forming units, pfu, n = 8; 2.2 × 108pfu, n = 7) or placebo (n = 4) at 0, 4 and 12 weeks. Magnitude, breadth and antiviral function of vaccine-induced T cells, cell-associated HIV-1 DNA in circulating CD4+ T cells and residual viremia in plasma were measured before and after vaccination. Results: 90% of subjects completed the vaccine regimen; there were no serious vaccine-related adverse events. The magnitude of HIVconsv-specific IFN-γ-secreting T cells was not significantly boosted in vaccinees when compared with placebos in ex vivo Elispot assays, due to greater than expected variation in HIV-specific T cell responses in the latter during the observation period. Ex vivo CD8+ T cell viral inhibitory capacity was modest but significantly increased post-vaccination with MVA.HIVconsv at the higher dose (p = 0.004) and was positively correlated with the frequency of HIVconsv-specific CD8+ CD107+ IFN-α± T cells (r = 0.57, p = 0.01). Total HIV-1 DNA and residual viral load did not change significantly from baseline in any group. Conclusions: Homologous prime-boost vaccination with MVA.HIVconsv was safe in HIV-positive ART-treated subjects but showed modest immunogenicity and did not significantly change the size of the viral reservoir. MVA.HIVconsv may be more effective when used in a heterologous prime-boost vaccination regimen and when combined with a latency-reversing agent. Clinical Trials Registration NCT01024842
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- 2017
262. Increased Stability and Breakdown of Brain Effective Connectivity During Slow-Wave Sleep: Mechanistic Insights from Whole-Brain Computational Modelling
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Jobst, Beatrice M, Hindriks, Rikkert, Laufs, Helmut, Tagliazucchi, E., Hahn, Gerald, Ponce-Alvarez, Adrián, Stevner, Angus B A, Kringelbach, Morten L, Deco, Gustavo, Jobst, Beatrice M, Hindriks, Rikkert, Laufs, Helmut, Tagliazucchi, E., Hahn, Gerald, Ponce-Alvarez, Adrián, Stevner, Angus B A, Kringelbach, Morten L, and Deco, Gustavo
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Recent research has found that the human sleep cycle is characterised by changes in spatiotemporal patterns of brain activity. Yet, we are still missing a mechanistic explanation of the local neuronal dynamics underlying these changes. We used whole-brain computational modelling to study the differences in global brain functional connectivity and synchrony of fMRI activity in healthy humans during wakefulness and slow-wave sleep. We applied a whole-brain model based on the normal form of a supercritical Hopf bifurcation and studied the dynamical changes when adapting the bifurcation parameter for all brain nodes to best match wakefulness and slow-wave sleep. Furthermore, we analysed differences in effective connectivity between the two states. In addition to significant changes in functional connectivity, synchrony and metastability, this analysis revealed a significant shift of the global dynamic working point of brain dynamics, from the edge of the transition between damped to sustained oscillations during wakefulness, to a stable focus during slow-wave sleep. Moreover, we identified a significant global decrease in effective interactions during slow-wave sleep. These results suggest a mechanism for the empirical functional changes observed during slow-wave sleep, namely a global shift of the brain's dynamic working point leading to increased stability and decreased effective connectivity.
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- 2017
263. Mapping the Milky Way in 5D with 170 Million Stars
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Joshua S. Speagle, Catherine Zucker, Ana Bonaca, Phillip A. Cargile, Benjamin D. Johnson, Angus Beane, Charlie Conroy, Douglas P. Finkbeiner, Gregory M. Green, Harshil M. Kamdar, Rohan Naidu, Hans-Walter Rix, Edward F. Schlafly, Aaron Dotter, Gwendolyn Eadie, Daniel J. Eisenstein, Alyssa A. Goodman, Jiwon Jesse Han, Andrew K. Saydjari, Yuan-Sen Ting, and Ioana A. Zelko
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Stellar distance ,the Milky Way ,Sky surveys ,Photometry ,Parallax ,Astrophysics ,QB460-466 - Abstract
We present Augustus , a catalog of distance, extinction, and stellar parameter estimates for 170 million stars from 14 mag < r < 20 mag and with ∣ b ∣ > 10° drawing on a combination of optical to near-infrared photometry from Pan-STARRS, 2MASS, UKIDSS, and unWISE along with parallax measurements from Gaia DR2 and 3D dust extinction maps. After applying quality cuts, we find 125 million objects have “high-quality” posteriors with statistical distance uncertainties of ≲10% for objects with well-constrained stellar types. This is a substantial improvement over the distance estimates derived from Gaia parallaxes alone and in line with the recent results from Anders et al. We find the fits are able to reproduce the dereddened Gaia color–magnitude diagram accurately, which serves as a useful consistency check of our results. We show that we are able to detect large, kinematically coherent substructures in our data clearly relative to the input priors, including the Monoceros Ring and the Sagittarius Stream, attesting to the quality of the catalog. Our results are publicly available at doi:10.7910/DVN/WYMSXV. An accompanying interactive visualization can be found at http://allsky.s3-website.us-east-2.amazonaws.com .
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- 2024
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264. The most relevant human brain regions for functional connectivity:Evidence for a dynamical workspace of binding nodes from whole-brain computational modelling
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Tim J. van Hartevelt, Henrique M. Fernandes, Gustavo Deco, Morten L. Kringelbach, and Angus B. A. Stevner
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0301 basic medicine ,Theoretical computer science ,Computer science ,Cognitive Neuroscience ,Models, Neurological ,Workspace ,Interconnectivity ,Measure (mathematics) ,Sistema nerviós -- Malalties -- Diagnòstic ,03 medical and health sciences ,0302 clinical medicine ,Encoding (memory) ,Neural Pathways ,Connectome ,Image Processing, Computer-Assisted ,medicine ,Humans ,business.industry ,Functional connectivity ,Cognitive flexibility ,Brain ,Cognition ,Human brain ,Magnetic Resonance Imaging ,Diagnòstic per la imatge ,Diffusion Magnetic Resonance Imaging ,Diffusion Tensor Imaging ,030104 developmental biology ,Order (biology) ,medicine.anatomical_structure ,Neurology ,Artificial intelligence ,business ,030217 neurology & neurosurgery ,Diffusion MRI - Abstract
In order to promote survival through flexible cognition and goal-directed behaviour, the brain has to optimize segregation and integration of information into coherent, distributed dynamical states. Certain organizational features of the brain have been proposed to be essential to facilitate cognitive flexibility, especially hub regions in the so-called rich club which show dense interconnectivity. These structural hubs have been suggested to be vital for integration and segregation of information. Yet, this has not been evaluated in terms of resulting functional temporal dynamics. A complementary measure covering the temporal aspects of functional connectivity could thus bring new insights into a more complete picture of the integrative nature of brain networks. Here, we use causal whole-brain computational modelling to determine the functional dynamical significance of the rich club and compare this to a new measure of the most functionally relevant brain regions for binding information over time (“dynamical workspace of binding nodes”). We found that removal of the iteratively generated workspace of binding nodes impacts significantly more on measures of integration and encoding of information capability than the removal of the rich club regions. While the rich club procedure produced almost half of the binding nodes, the remaining nodes have low degree yet still play a significant role in the workspace essential for binding information over time and as such goes beyond a description of the structural backbone. GD was supported by the ERC Advanced Grant: DYSTRUCTURE (n. 295129), by the Spanish Research Project SAF2010-16085 and the FP7-ICT BrainScales. MLK was supported by the ERC Consolidator Grant: CAREGIVING (n. 615539), TrygFonden Charitable Foundation and by Center for Music in the Brain, funded by the Danish National Research Foundation (DNRF117).
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- 2016
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265. Single or Multi-Frequency generators in on-going brain activity: a mechanistic whole-brain model of empirical MEG data
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Joana Cabral, Mark W. Woolrich, Tim J. van Hartevelt, Morten L. Kringelbach, Angus B. A. Stevner, and Gustavo Deco
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Hopf bifurcation ,Physics ,0303 health sciences ,Signal generator ,Steady state (electronics) ,Quantitative Biology::Neurons and Cognition ,Brain activity and meditation ,Fundamental frequency ,Stability (probability) ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,symbols ,Statistical physics ,030217 neurology & neurosurgery ,030304 developmental biology ,Network model ,Envelope (waves) - Abstract
During rest, envelopes of band-limited on-going MEG signals co-vary across the brain in consistent patterns, which have been related to resting-state networks measured with fMRI. To investigate the genesis of such envelope correlations, we consider a whole-brain network model assuming two distinct fundamental scenarios: one where each brain area generates oscillations in a single frequency, and a novel one where each brain area can generate oscillations in multiple frequency bands. The models share, as a common generator of damped oscillations, the normal form of a supercritical Hopf bifurcation operating at the critical border between the steady state and the oscillatory regime. The envelopes of the simulated signals are compared with empirical MEG data using new methods to analyse the envelope dynamics in terms of their phase coherence and stability across the spectrum of carrier frequencies.Considering the whole-brain model with a single frequency generator in each brain area, we obtain the best fit with the empirical MEG data when the fundamental frequency is tuned at 12Hz. However, when multiple frequency generators are placed at each local brain area, we obtain an improved fit of the spatio-temporal structure of on-going MEG data across all frequency bands. Our results indicate that the brain is likely to operate on multiple frequency channels during rest, introducing a novel dimension for future models of large-scale brain activity.
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- 2016
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266. Uncovering the underlying mechanisms and whole-brain dynamics of therapeutic deep brain stimulation for Parkinsons disease
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Gustavo Deco, Alexander L. Green, Angus B. A. Stevner, Joshua Kahan, Henrique M. Fernandes, Marwan Hariz, Tipu Z. Aziz, Morten L. Kringelbach, Tim J. van Hartevelt, Laura Mancini, Tarek A. Yousry, Thomas Foltynie, John S. Thornton, Patricia Limousin, Victor M. Saenger, Karl J. Friston, and Ludvic Zrinzo
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0303 health sciences ,Parkinson's disease ,Deep brain stimulation ,Resting state fMRI ,business.industry ,medicine.medical_treatment ,Stimulation ,Disease ,medicine.disease ,behavioral disciplines and activities ,3. Good health ,nervous system diseases ,03 medical and health sciences ,0302 clinical medicine ,surgical procedures, operative ,nervous system ,medicine ,Effective treatment ,business ,Neuroscience ,therapeutics ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
Deep brain stimulation (DBS) for Parkinson's disease is a highly effective treatment in controlling otherwise debilitating symptoms yet the underlying brain mechanisms are currently not well understood. We used whole-brain computational modeling to disclose the effects of DBS ON and OFF during collection of resting state fMRI in ten Parkinson's Disease patients. Specifically, we explored the local and global impact of DBS in creating asynchronous, stable or critical oscillatory conditions using a supercritical bifurcation model. We found that DBS shifts the global brain dynamics of patients nearer to that of healthy people by significantly changing the bifurcation parameters in brain regions implicated in Parkinson's Disease. We also found higher communicability and coherence brain measures during DBS ON compared to DBS OFF. Finally, by modeling stimulation we identified possible novel DBS targets. These results offer important insights into the underlying effects of DBS, which may in time offer a route to more efficacious treatments.
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- 2016
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267. An unusual cutaneous complication of BCG immunotherapy
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Lloyd-Lavery, A, Ali, I, Espinosa, O, Angus, B, and Turner, RJ
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- 2016
268. Predictors of bacterial pneumonia in Evaluation of Subcutaneous Interleukin-2 in a Randomized International Trial (ESPRIT)
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Pett, SL, Carey, C, Lin, E, Wentworth, D, Lazovski, J, Miró, JM, Gordin, F, Angus, B, Rodriguez-Barradas, M, Rubio, R, Tambussi, G, Cooper, DA, and Emery, S
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BACKGROUND AND OBJECTIVES: Bacterial pneumonia still contributes to morbidity/mortality in HIV infection despite effective combination antiretroviral therapy (cART). Evaluation of Subcutaneous Interleukin-2 in a Randomized International Trial (ESPRIT), a trial of intermittent recombinant interleukin-2 (rIL-2) with cART vs. cART alone (control arm) in HIV-infected adults with CD4 counts ≥300cells/μL, offered the opportunity to explore associations between bacterial pneumonia and rIL-2, a cytokine that increases the risk of some bacterial infections. METHODS: Baseline and time-updated factors associated with first-episode pneumonia on study were analysed using multivariate proportional hazards regression models. Information on smoking/pneumococcal vaccination history was not collected. RESULTS: IL-2 cycling was most intense in years 1-2. Over ≈7 years, 93 IL-2 [rate 0.67/100 person-years (PY)] and 86 control (rate 0.63/100 PY) patients experienced a pneumonia event [hazard ratio (HR) 1.06; 95% confidence interval (CI) 0.79, 1.42; P=0.68]. Median CD4 counts prior to pneumonia were 570cells/μL (IL-2 arm) and 463cells/μL (control arm). Baseline risks for bacterial pneumonia included older age, injecting drug use, detectable HIV viral load (VL) and previous recurrent pneumonia; Asian ethnicity was associated with decreased risk. Higher proximal VL (HR for 1 log(10) higher VL 1.28; 95% CI 1.11, 1.47; P
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- 2016
269. Pharmacokinetic-pharmacodynamic evaluation of ceftazidime continuous infusion vs intermittent bolus injection in septicaemic melioidosis
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Angus, B. J., Smith, M. D., Suputtamongkol, Y., Mattie, H., Walsh, A. L., Wuthiekanun, V., Chaowagul, W., and Nicholas White
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Errata - Abstract
AIMS: Experimental studies have suggested that constant intravenous infusion would be preferable to conventional intermittent bolus administration of beta-lactam antibiotics for serious Gram-negative infections. Severe melioidosis (Burkholderia pseudomallei infection) carries a mortality over 40% despite treatment with high dose ceftazidime. The aim of this study was to measure the pharmacokinetic and pharmacodynamic effects of continuous infusion of ceftazidime vs intermittent bolus dosing in septicaemic melioidosis. METHODS: Patients with suspected septicaemic melioidosis were randomised to receive ceftazidime 40 mg kg(-1) 8 hourly by bolus injection or 4 mg kg(-1) h(-1) by constant infusion following a 12 mg kg(-1) priming dose and pharmacokinetic and pharmacodynamic parameters were compared. RESULTS: Of the 34 patients studied 16 (59%) died. Twenty patients had cultures positive for B. pseudomallei of whom 12 (60%) died. The median MIC90 of B. pseudomallei was 2 mg l(-1), giving a minimum target concentration (4*MIC) of 8 mg l(-1). The median (range) estimated total apparent volume of distribution, systemic clearance and terminal elimination half-lives of ceftazidime were 0.468 (0.241-0. 573) l kg(-1), 0.058 (0.005-0.159) l kg(-1) h(-1) and 7.74 (1.95-44.71) h, respectively. Clearance of ceftazidime and creatinine clearance were correlated closely (r = 0.71; P < 0.001) and there was no evidence of significant nonrenal clearance. CONCLUSIONS: Simulations based on these data and the ceftazidime sensitivity of the B. pseudomallei isolates indicated that administration by constant infusion would allow significant dose reduction and cost saving. With conventional 8 h intermittent dosing to patients with normal renal function, plasma ceftazidime concentrations could fall below the target concentration but this would be unlikely with a constant infusion. Correction for renal failure, which is common in patients with meliodosis is Clearance = k(*) creatinine clearance where k = 0.72. Calculation of a loading dose gives median (range) values of loading dose, DL of 18.7 mg kg(-1) (9.5-23) and infusion rate I = 3.5 mg k(-1) h(-1) (0.4-13) (which equals 84 mg kg(-1) day(-1)). A nomogram for adjustment in renal failure is given.
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- 2016
270. Topics in international health: Malaria CD-Rom
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Angus, B
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- 2016
271. Comprehensive Cardiac Magnetic Resonance Reveals HIV is Associated with High Burden of Myocardial Disease
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Holloway, C, Ntusi, N, Suttie, J, Mahmod, M, Clutton, G, Hancock, G, Wainwright, E, Angus, B, Asaad, M, Beak, P, Clarke, K, Neubauer, S, and Dorrell, L
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- 2016
272. One hundred and twelve infected arthroplasties treated with 'DAIR' (debridement, antibiotics and implant retention): antibiotic duration and outcome (vol 63, pg 1264, 2009)
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Byren, I, Bejon, P, Atkins, BL, Angus, B, Masters, S, McLardy-Smith, P, Gundle, R, and Berendt, A
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- 2016
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273. What Makes Good Teaching?
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Cameron, Angus B.
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- 1919
274. S-R Bonds
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McAffee, Boyd, Harmon, Millard, Hall, Gertrude M., Crow, Lester D., Mayer, Frederick, Dennis, Charles M., Morrison, J. Cayce, Lerner, Arthur, Campbell, Carl, Henrich, Louis J., Current, F. B., Howe, Ino, Rothwell, Angus B., McKibben, Robert T., and Menke, Robert F.
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- 1954
275. A Union of Hearts and Hands
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Rothwell, Angus B.
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- 1953
276. Host and disease factors are associated with cognitive function in European HIV-infected adults prior to initiation of antiretroviral therapy
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Winston, A, Stohr, W, Antinori, A, Arenas Pinto, A, Llibre, J, Amieva, H, Cabie, A, Williams, I, Di Perri, G, Tellez, M, Rockstroh, J, Babiker, A, Pozniak, A, Raffi, F, Richert, L, Dedes, N, Chene, G, Allavena, C, Autran, B, Bucciardini, R, Vella, S, Horban, A, Arribas, J, Boffito, M, Pillay, D, Franquet, X, Schwarze, S, Grarup, J, Fischer, A, Wallet, C, Diallo, A, Molina, J, Saillard, J, Moecklinghoff, C, Stellbrink, H, Leeuwen, R, Gatell, J, Sandstrom, E, Flepp, M, Ewings, F, George, E, Hudson, F, Pearce, G, Quercia, R, Rogatto, F, Leavitt, R, Nguyen, B, Goebel, F, Marcotullio, S, Kaur, N, Sasieni, P, Spencer Drake, C, Peto, T, Miller, V, Arnault, F, Boucherie, C, Jean, D, Paniego, V, Rouch, E, Schwimmer, C, Soussi, M, Taieb, A, Termote, M, Touzeau, G, Cursley, A, Dodds, W, Hoppe, A, Kummeling, I, Pacciarini, F, Paton, N, Russell, C, Taylor, K, Ward, D, Aagaard, B, Eid, M, Gey, D, Jensen, B, Jakobsen, M, Jansson, P, Jensen, K, Joensen, Z, Larsen, E, Pahl, C, Pearson, M, Nielsen, B, Reilev, S, Christ, I, Lathouwers, D, Manting, C, Mendy, B, Metro, A, Couffin Cadiergues, S, Knellwolf, A, Palmisiano, L, Aznar, E, Barea, C, Cotarelo, M, Esteban, H, Girbau, I, Moyano, B, Ramirez, M, Saiz, C, Sanchez, I, Yllescas, M, Binelli, A, Colasanti, V, Massella, M, Anagnostou, O, Gioukari, V, Touloumi, G, Schmied, B, Rieger, A, Vetter, N, Wit, S, Florence, E, Vandekerckhove, L, Gerstoft, J, Mathiesen, L, Katlama, C, Cheret, A, Dupon, M, Ghosn, J, Girard, P, Goujard, C, Levy, Y, Morlat, P, Neau, D, Obadia, M, Perre, P, Piroth, L, Reynes, J, Tattevin, P, Ragnaud, J, Weiss, L, Yazdan, Y, Yeni, P, Zucman, D, Behrens, G, Esser, S, Fatkenheuer, G, Hoffmann, C, Jessen, H, Schmidt, R, Stephan, C, Unger, S, Hatzakis, A, Daikos, G, Papadopoulos, A, Skoutelis, A, Banhegyi, D, Mallon, P, Mulcahy, F, Andreoni, M, Bonora, S, Castelli, F, Monforte, A, Galli, M, Lazzarin, A, Mazzotta, F, Carlo, T, Vullo, V, Prins, J, Richter, C, Verhagen, D, Eeden, A, Doroana, M, Antunes, F, Maltez, F, Sarmento Castro, R, Garcia, J, Aldeguer, J, Clotet, B, Domingo, P, Knobel, H, Marquez, M, Miralles, M, Portilla, J, Soriano, V, Thalme, A, Blaxhult, A, Gisslen, M, Fox, J, Gompels, M, Herieka, E, Johnson, M, Leen, C, Teague, A, Boyd, M, Moller, N, Frosig, E, Moing, V, Wit, F, Kowalska, J, Berenguer, J, Moreno, S, Muhller, N, Torok, E, Post, F, Angus, B, Calvez, V, Boucher, C, Collins, S, Dunn, D, Lambert, S, Marcelin, A, Perno, Cf, White, E, Ammassari, A, Stoehr, W, Odermarsky, M, Smith, C, Thiebaut, R, Laserna, B, Castagna, A, Furrer, H, Mocroft, A, Reiss, P, Fragola, V, Lauriola, M, Murri, R, Nieuwkerk, P, Spire, B, Volny Anne, A, West, B, Maria, J, Braggion, M, Foca, E, Amsterdam institute for Infection and Immunity, Infectious diseases, Global Health, Amsterdam Public Health, Medical Psychology, Winston, A., Stohr, W., Antinori, A., Arenas-Pinto, A., Llibre, J. M., Amieva, H., Cabie, A., Williams, I., Di Perri, G., Tellez, M. J., Rockstroh, J., Babiker, A., Pozniak, A., Raffi, F., Richert, L., on beahlf of NEAT 001/Agence Nationale de Recherche sur le SIDA (ANRS) 143 Study, Group, and Castagna, A.
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Gerontology ,Male ,Antiretroviral naïve ,antiretroviral naïve ,HIV Infections ,0302 clinical medicine ,HIV ,antiretroviral naïve ,cognitive ,neuropsychological tests ,Interquartile range ,Verbal fluency test ,HIV Infection ,Pharmacology (medical) ,030212 general & internal medicine ,Sida ,Psychomotor learning ,education.field_of_study ,biology ,NEAT 001/Agence Nationale de Recherche sur le SIDA (ANRS) 143 Study Group ,Health Policy ,Cognition ,Middle Aged ,Settore MED/07 - Microbiologia e Microbiologia Clinica ,Cognitive test ,Cognitive ,Neuropsychological tests ,Infectious Diseases ,Europe ,Anti-Retroviral Agents ,Population study ,Female ,Human ,Adult ,medicine.medical_specialty ,Population ,03 medical and health sciences ,Virology ,Internal medicine ,medicine ,Humans ,Cognitive Dysfunction ,Psychological Tests ,education ,business.industry ,1103 Clinical Sciences ,biology.organism_classification ,Psychological Test ,neuropsychological test ,Anti-Retroviral Agent ,business ,030217 neurology & neurosurgery - Abstract
OBJECTIVES: Deficits in cognitive function remain prevalent in HIV-infected individuals. The aim of this European multicentre study was to assess factors associated with cognitive function in antiretroviral therapy (ART)-naive HIV-infected subjects at the time of enrolment in the NEAT 001/Agence Nationale de Recherche sur le SIDA (ANRS) 143 study.METHODS: Prior to starting ART, seven cognitive tests exploring domains including episodic memory, verbal fluency, executive function and psychomotor speed were administered with scores standardized to z-score using the study population sample mean and standard deviation. The primary measure was overall z-score average (NPZ). We assessed associations between baseline factors and test results using multivariable regression models.RESULTS: Of 283 subjects with baseline cognitive assessments, 90% were male and 12% of black ethnicity. Median (interquartile range) age, years of education, years of known HIV infection, baseline CD4 count and baseline HIV RNA were 39 (31, 47) years, 13 (11, 17) years, 1 (0, 4) years, 344 (279, 410) cells/μL and 4.74 (4.28, 5.14) log10 HIV-1 RNA copies/mL, respectively. Forty per cent were current smokers. Factors significantly associated with poorer overall cognitive performance in multivariable models included older age, shorter duration of education, black ethnicity, lower height, and lower plasma HIV RNA.CONCLUSIONS: In this large, European-wide, ART-naive population with relatively preserved immunity and early HIV infection, cognitive function scores at the time of ART initiation were associated with demographic and HIV-disease factors. (Less)
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- 2016
277. Analytical and sampling constraints in 210Pb dating
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Angus B. MacKenzie, John G. Farmer, S.M.L. Hardie, Lorna J. Eades, and Ian D. Pulford
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Grande bretagne ,Empirical data ,Environmental Engineering ,Ecology ,Sampling (statistics) ,Magnitude (mathematics) ,Geophysics ,Pollution ,Age bias ,Constant rate ,Environmental Chemistry ,Waste Management and Disposal ,Sediment core ,Royaume uni ,Geology - Abstract
210Pb dating provides a valuable, widely used means of establishing recent chronologies for sediments and other accumulating natural deposits. The Constant Rate of Supply (CRS) model is the most versatile and widely used method for establishing 210Pb chronologies but, when using this model, care must be taken to account for limitations imposed by sampling and analytical factors. In particular, incompatibility of finite values for empirical data, which are constrained by detection limit and core length, with terms in the age calculation, which represent integrations to infinity, can generate erroneously old ages for deeper sections of cores. The bias in calculated ages increases with poorer limit of detection and the magnitude of the disparity increases with age. The origin and magnitude of this effect are considered below, firstly for an idealised, theoretical 210Pb profile and secondly for a freshwater lake sediment core. A brief consideration is presented of the implications of this potential artefact for sampling and analysis.
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- 2011
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278. Investigation of lead and zinc dispersion from an abandoned mine site at Tyndrum, Scotland, using tree bark measurements
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Mansor, Nurlidia, Pulford, Ian D., and MacKenzie, Angus B.
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- 2006
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279. Determining depleted uranium (DU) contamination in soils and salt marsh sediments in the vicinity of DU munitions testing sites in SW Scotland and NW England, UK
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Oliver, Ian W., MacKenzie, Angus B., Ellam, Rob M., Graham, Margaret C., and Farmer, John G.
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- 2006
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280. Associations and mobility of uranium in soils near a depleted uranium (DU) weapons testing site, SW Scotland
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Graham, Margaret C., Farmer, John G., Oliver, Ian W., MacKenzie, Angus B., and Ellam, Robert M.
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- 2006
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281. Climate variability over the last two millennia in the North American Monsoon region, recorded in laminated lake sediments from Laguna de Juanacatlán, Mexico
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Anders Noren, Sarah E. Metcalfe, Angus B. MacKenzie, Sarah J. Davies, and Matthew Jones
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Archeology ,Global and Planetary Change ,Ecology ,North American Monsoon ,Paleontology ,Climate change ,Monsoon ,Oceanography ,Paleoclimatology ,Precipitation ,Quaternary ,Cenozoic ,Geology ,Holocene ,Earth-Surface Processes - Abstract
High-resolution titanium (Ti) data obtained using an ITRAX XRF core scanner from a laminated sediment core from the Laguna de Juanacatlán, western central Mexico yield a unique high-resolution record of runoff (precipitation) change for the last 2000 years. In the absence of reliable, long-term meteorological records, comparison of the Ti data with information from the rich Spanish colonial period archives and the post-Independence period, confirms that Ti is a proxy for runoff. This interpretation is supported by comparison with other high-resolution archives from the surrounding region, primarily tree rings and other lake sediment sequences. The Juanacatlán Ti record is therefore a proxy for summer, monsoonal rainfall. The record provides new evidence from the Pacific margin of tropical North America of the occurrence of dry conditions through much of the Classic period ( c. AD 300—900), and wetter conditions during the later Medieval period ( c. AD 1200—1350). The period commonly known as the ‘Little Ice Age’ (LIA) shows considerable variability, with dry conditions in the early part ( c. AD 1400—1600) and wetter conditions, punctuated by multiyear droughts through the eighteenth century. A notable feature of the record is the apparent decoupling of lacustrine sedimentation from the climate since the mid-twentieth century, possibly resulting from anthropogenic disturbance. Preliminary interpretations of the Ti record indicate that patterns are consistent with changes in monsoon strength associated with ENSO and solar forcing over the last two millennia.
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- 2010
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282. The character, volume and implications of sediment impounded in mill dams in Scotland: the case of the Baldernock Mill dam in East Dunbartonshire
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Paul Bishop, Ian D. Pulford, Esperanza Muñoz-Salinas, Angus B. MacKenzie, and Jan McKibbin
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Hydrology ,geography ,geography.geographical_feature_category ,Flood myth ,Bedrock ,Sediment ,Stratigraphic section ,General Earth and Planetary Sciences ,Mill ,Historical maps ,Glacial period ,Geology ,General Environmental Science ,Chronology - Abstract
Reservoir sedimentation provides a valuable source of data on sediment flux. This paper assesses the record of sedimentation in the Baldernock Mill dam, a small mill dam in western Scotland. That record is based on the volume of sediment in the dam, and the detailed analysis of a continuously sampled stratigraphic section through the impounded sediment, with a chronology for mill dam construction and subsequent breaching based on historical maps and the impounded sediment’s content of 137Cs and lead isotopes. The mill dam was constructed in c. 1820, was initially partially breached in the late nineteenth or early twentieth century and then fully breached by about the mid 1920s. The dam trapped relatively low volumes of sediment and the correspondingly low rate of sediment flux indicated by the volume of impounded sediment reflects the dam’s very low trap efficiency. The basal Unit 1 in the impounded sediments was deposited between dam construction and the initial breaching of the wall. The unit consists of repeated ‘triplets’ of a basal sand (flood deposit) grading upwards into a mud deposit (post-flood deposition), which is in turn overlain by an organic-rich layer of leaves and twigs (the subsequent autumn leaf fall). Unit 2 is similar to Unit 1 but lacks the organic layer, indicating the lack of ongoing standing water to trap the autumn leaf fall, and Unit 3 was deposited after full breaching of the wall. Mill dams in Scotland generally impound small steep bedrock channels – the latter reflecting a strong glacial legacy in Scotland – and are only small structures designed to ensure water for mills during dry periods in a climate of otherwise generally moderate to high and reliable rainfall. The small sizes of these dams and their low wall heights mean that they trap relatively low volumes of sediment that have minimal to minor downstream impacts if the dams fail.
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- 2010
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283. Detecting the near-surface redox front in crystalline bedrock using fracture mineral distribution, geochemistry and U-series disequilibrium
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Henrik Drake, Eva-Lena Tullborg, and Angus B. MacKenzie
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Calcite ,Radionuclide ,Goethite ,Fracture (mineralogy) ,Geochemistry ,Radioactive waste ,Mineralogy ,engineering.material ,Pollution ,Redox ,chemistry.chemical_compound ,chemistry ,Geochemistry and Petrology ,visual_art ,visual_art.visual_art_medium ,engineering ,Environmental Chemistry ,Pyrite ,Groundwater ,Geology - Abstract
Oxidizing conditions normally prevail in surface waters and near-surface groundwaters, but there is usually a change to reducing conditions in groundwater at greater depth. Dissolved O2 originally present is consumed through biogenic and inorganic reactions along the flow paths. Fracture minerals participate in these reactions and the fracture mineralogy and geochemistry can be used to trace the redox front. An important task in the safety assessment of a potential repository for the disposal of nuclear waste in crystalline bedrock, at an approximate depth of 500 m in Sweden, is to demonstrate that reducing conditions can be maintained for a long period of time. Oxygen may damage the Cu canisters that host nuclear waste; additionally, in the event of a canister failure, oxidizing conditions may increase the mobility of some radionuclides. The present study of the near-surface redox front is based on mineralogical (redox-sensitive minerals), geochemical (redox-sensitive elements) and U-series disequilibrium investigations of mineral coatings along open fractures. The fractures have been sampled along drill cores from closely spaced, 100 m deep boreholes, which were drilled during the site investigation work in the Laxemar area, south-eastern Sweden, carried out by the Swedish Nuclear Fuel and Waste Management Co. (SKB). The distribution of the redox-sensitive minerals pyrite and goethite in open fractures shows that the redox front (switch from mainly goethite to mainly pyrite in the fractures) generally occurs at about 15–20 m depth. Calcite leaching by recharging water is indicated in the upper 20–30 m and positive Ce-anomalies suggest oxidation of Ce down to 20 m depth. The U-series radionuclides show disequilibrium in most of the samples, indicating mobility of U during the last 1 Ma. In the upper 20 m, U is mainly removed (due to oxidation) or has experienced complex removal and/or deposition. At depths of 35–55 m, both deposition and removal of U are indicated. Below 55 m, recent deposition of U is generally indicated which suggests removal of U near surface (oxidation) and deposition of U below the redox front. Scattered goethite occurrences below the general redox front (down to ca 80 m) and signs of U removal at 35–55 m mostly correlate with sections of high transmissivity (and/or high fracture frequencies). This shows that highly transmissive fractures are generally required to allow oxygenated groundwaters at depth greater than ca 30 m. Removal of U (oxidation) below 55 m within the last 300 ka is not observed. Although penetration of glacial waters to great depths has been confirmed in the study area, their potential O2 load seems to have been reduced near the surface.
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- 2009
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284. Source term characterisation using concentration trends and geochemical associations of Pb and Zn in river sediments in the vicinity of a disused mine site: Implications for contaminant metal dispersion processes
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Angus B. MacKenzie, Laura Hastings, Shane Donatello, and Ian D. Pulford
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Pollution ,Geologic Sediments ,Health, Toxicology and Mutagenesis ,media_common.quotation_subject ,Sorting (sediment) ,Industrial Waste ,Fractionation ,Toxicology ,Dispersion (geology) ,Mining ,chemistry.chemical_compound ,Rivers ,Soil Pollutants ,Aqua regia ,Water pollution ,media_common ,Hydrology ,Sediment ,General Medicine ,Zinc ,Lead ,Scotland ,chemistry ,Environmental chemistry ,Environmental science ,Water quality ,Water Pollutants, Chemical ,Environmental Monitoring - Abstract
River sediment at a disused lead–zinc mine was analysed to provide an understanding of the chemical nature of the source term for contaminated sediment exported from the site. Changes in concentration and geochemical associations of Pb and Zn were measured using aqua regia digestion and the BCR sequential extraction procedure. Sediment in the immediate vicinity of the mine was highly contaminated with Pb (max. c. 11,000 mg kg −1 ) and Zn (max. c. 30,000 mg kg −1 ), but these values declined rapidly within 1 km of the mine due to dilution and hydraulic sorting. Lead fractionation changed from being predominantly in the reducible fraction to being in the acetic acid-extractable fraction, whereas Zn was predominantly in the residual fraction. This material is transported as fine sediment in the river system.
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- 2009
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285. Randomized controlled trials in neurosurgery: an observational analysis of trial discontinuation and publication outcome
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Jamjoom, Aimun A. B., primary, Gane, Angus B., additional, and Demetriades, Andreas K., additional
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- 2017
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286. Uncovering the underlying mechanisms and whole-brain dynamics of deep brain stimulation for Parkinson’s disease
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Saenger, Victor M., primary, Kahan, Joshua, additional, Foltynie, Tom, additional, Friston, Karl, additional, Aziz, Tipu Z., additional, Green, Alexander L., additional, van Hartevelt, Tim J., additional, Cabral, Joana, additional, Stevner, Angus B. A., additional, Fernandes, Henrique M., additional, Mancini, Laura, additional, Thornton, John, additional, Yousry, Tarek, additional, Limousin, Patricia, additional, Zrinzo, Ludvic, additional, Hariz, Marwan, additional, Marques, Paulo, additional, Sousa, Nuno, additional, Kringelbach, Morten L., additional, and Deco, Gustavo, additional
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- 2017
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287. Increased Stability and Breakdown of Brain Effective Connectivity During Slow-Wave Sleep: Mechanistic Insights from Whole-Brain Computational Modelling
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Jobst, Beatrice M., primary, Hindriks, Rikkert, additional, Laufs, Helmut, additional, Tagliazucchi, Enzo, additional, Hahn, Gerald, additional, Ponce-Alvarez, Adrián, additional, Stevner, Angus B. A., additional, Kringelbach, Morten L., additional, and Deco, Gustavo, additional
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- 2017
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288. The host phylogeny determines viral infectivity and replication across Staphylococcus host species.
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Sarah K Walsh, Ryan M Imrie, Marta Matuszewska, Gavin K Paterson, Lucy A Weinert, Jarrod D Hadfield, Angus Buckling, and Ben Longdon
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
Virus host shifts, where a virus transmits to and infects a novel host species, are a major source of emerging infectious disease. Genetic similarity between eukaryotic host species has been shown to be an important determinant of the outcome of virus host shifts, but it is unclear if this is the case for prokaryotes where anti-virus defences can be transmitted by horizontal gene transfer and evolve rapidly. Here, we measure the susceptibility of 64 strains of Staphylococcaceae bacteria (48 strains of Staphylococcus aureus and 16 non-S. aureus species spanning 2 genera) to the bacteriophage ISP, which is currently under investigation for use in phage therapy. Using three methods-plaque assays, optical density (OD) assays, and quantitative (q)PCR-we find that the host phylogeny explains a large proportion of the variation in susceptibility to ISP across the host panel. These patterns were consistent in models of only S. aureus strains and models with a single representative from each Staphylococcaceae species, suggesting that these phylogenetic effects are conserved both within and among host species. We find positive correlations between susceptibility assessed using OD and qPCR and variable correlations between plaque assays and either OD or qPCR, suggesting that plaque assays alone may be inadequate to assess host range. Furthermore, we demonstrate that the phylogenetic relationships between bacterial hosts can generally be used to predict the susceptibility of bacterial strains to phage infection when the susceptibility of closely related hosts is known, although this approach produced large prediction errors in multiple strains where phylogeny was uninformative. Together, our results demonstrate the ability of bacterial host evolutionary relatedness to explain differences in susceptibility to phage infection, with implications for the development of ISP both as a phage therapy treatment and as an experimental system for the study of virus host shifts.
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- 2023
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289. Antagonistic Mobile Genetic Elements Can Counteract Each Other’s Effects on Microbial Community Composition
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Meaghan Castledine, Arthur Newbury, Rai Lewis, Christian Hacker, Sean Meaden, and Angus Buckling
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bacteriophages ,indirect interactions ,“kill the winner” dynamics ,microbial communities ,mobile genetic elements ,plasmids ,Microbiology ,QR1-502 - Abstract
ABSTRACT Bacteriophages (“phages”) are hypothesized to be key drivers of bacterial population dynamics, driving microbial community composition, but empirical support for this is mixed. One reason why phages may have a less-than-expected impact on community composition is that many different phages and other mobile genetic elements (MGEs) interact with each bacterium. For instance, the same phage may have higher or lower costs to different bacterial strains or species. Assuming that resistance or susceptibility to MGE infection is not consistent across all MGEs, a simple prediction is that the net effect of MGEs on each bacterial taxon may converge with an increasing number of interactions with different MGEs. We formalized this prediction using in silico population dynamics simulations and then carried out experiments using three bacterial species, one generalist conjugative plasmid, and three species-specific phages. While the presence of only phages or only the plasmid altered community structure, these differential effects on community structure canceled out when both were together. The effects of MGEs were largely indirect and could not be explained by simple pairwise bipartite interactions (i.e., between each MGE and each bacterial species). Our results suggest that the effects of MGEs may be overestimated by studies that focus on a single MGE and not on interactions among multiple MGEs. IMPORTANCE While bacteriophages (“phages”) are often cited as some of the key drivers of microbial diversity, evidence for this is greatly mixed. We demonstrate, in silico and experimentally, that the impact of phages, an example of a mobile genetic element (MGE), on community structure can diminish with increasing MGE diversity. This is because MGEs can have diverse effects on host fitness, and therefore as diversity increases, their individual effects cancel out, returning communities back to an MGE-free state. In addition, interactions in mixed-species and MGE communities could not be predicted from simple pairwise interactions, highlighting the difficulty in generalizing a MGE’s effect from pairwise studies.
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- 2023
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290. 129I/127I ratios in surface waters of the English Lake District
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Angus B. MacKenzie, Rob M. Ellam, Stewart P.H.T. Freeman, Colin Maden, Mariko Atarashi-Andoh, Hans-Arno Synal, Sheng Xu, A. Dougans, Valerie Olive, C. Schnabel, and Gordon Cook
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Shore ,Hydrology ,geography ,medicine.medical_specialty ,geography.geographical_feature_category ,Range (biology) ,Pollution ,Radioecology ,Oceanography ,Geochemistry and Petrology ,medicine ,Environmental Chemistry ,Environmental science ,Seawater ,Energy source ,Effluent ,Surface water ,Accelerator mass spectrometry - Abstract
Accelerator Mass Spectrometry (AMS) was used to measure 129 I/ 127 I ratios in surface sea, lake, and river water samples collected in 2004 and 2005 from the English Lake District and from SW Scotland, areas which are in relatively close proximity to the Sellafield nuclear fuel reprocessing plant in NW England. The 129 I/ 127 I ratios in surface water collected from the shore of the Irish Sea were in the range 2.8 × 10 −6 to 8.2 × 10 −6 . These ratios are one order of magnitude higher than that of seawater collected from the Irish Sea in 1992, correlating with the increase in 129 I content of the Sellafield liquid effluent discharge over the last decade. The 129 I/ 127 I ratios in lakes in the Lake District were in the range 0.7 × 10 −6 to 6.4 × 10 −6 and decreased exponentially as a function of distance from Sellafield. Consideration of the relative variation of stable I concentrations and 129 I/ 127 I ratios suggests that Sellafield gaseous discharges may be the dominant source of 129 I to the lakes.
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- 2007
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291. Evidence for a Caregiving Instinct: Rapid Differentiation of Infant from Adult Vocalizations Using Magnetoencephalography
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Katherine S, Young, Christine E, Parsons, Else-Marie, Jegindoe Elmholdt, Mark W, Woolrich, Tim J, van Hartevelt, Angus B A, Stevner, Alan, Stein, and Morten L, Kringelbach
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Adult ,Male ,magnetoencephalography ,vocalization ,caregiving ,Brain ,Infant ,Crying ,Original Articles ,Awareness ,Neuropsychological Tests ,Time ,Young Adult ,Acoustic Stimulation ,Caregivers ,Pattern Recognition, Physiological ,Auditory Perception ,Humans ,Female ,orbitofrontal cortex ,Evoked Potentials - Abstract
Crying is the most salient vocal signal of distress. The cries of a newborn infant alert adult listeners and often elicit caregiving behavior. For the parent, rapid responding to an infant in distress is an adaptive behavior, functioning to ensure offspring survival. The ability to react rapidly requires quick recognition and evaluation of stimuli followed by a co-ordinated motor response. Previous neuroimaging research has demonstrated early specialized activity in response to infant faces. Using magnetoencephalography, we found similarly early (100–200 ms) differences in neural responses to infant and adult cry vocalizations in auditory, emotional, and motor cortical brain regions. We propose that this early differential activity may help to rapidly identify infant cries and engage affective and motor neural circuitry to promote adaptive behavioral responding, before conscious awareness. These differences were observed in adults who were not parents, perhaps indicative of a universal brain-based “caregiving instinct.”
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- 2015
292. Evidence for a caregiving instinct: rapid differentiation of infant from adult vocalizations using magnetoencephalography
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Young, Katherine S, Parsons, Christine E, Jegindoe Elmholdt, Else-Marie, Woolrich, Mark W, van Hartevelt, Tim J, Stevner, Angus B A, Stein, Alan, and Kringelbach, Morten L
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Adult ,Male ,Research Support, Non-U.S. Gov't ,Brain ,Infant ,Magnetoencephalography ,Crying ,Awareness ,Neuropsychological Tests ,Time ,Young Adult ,Acoustic Stimulation ,Caregivers ,Pattern Recognition, Physiological ,Auditory Perception ,Journal Article ,Humans ,Female ,Evoked Potentials - Abstract
Crying is the most salient vocal signal of distress. The cries of a newborn infant alert adult listeners and often elicit caregiving behavior. For the parent, rapid responding to an infant in distress is an adaptive behavior, functioning to ensure offspring survival. The ability to react rapidly requires quick recognition and evaluation of stimuli followed by a co-ordinated motor response. Previous neuroimaging research has demonstrated early specialized activity in response to infant faces. Using magnetoencephalography, we found similarly early (100-200 ms) differences in neural responses to infant and adult cry vocalizations in auditory, emotional, and motor cortical brain regions. We propose that this early differential activity may help to rapidly identify infant cries and engage affective and motor neural circuitry to promote adaptive behavioral responding, before conscious awareness. These differences were observed in adults who were not parents, perhaps indicative of a universal brain-based "caregiving instinct."
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- 2015
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293. Feature- versus rule-based generalization in rats, pigeons and humans
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Stephen E. G. Lea, Elisa Maes, Jan De Houwer, Tom Beckers, Rudi D'Hooge, Guido De Filippo, Andy J. Wills, Angus B. Inkster, R&D centraal, Neurology, and Klinische Psychologie (Psychologie, FMG)
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Male ,Matching to sample ,COLUMBA-LIVIA ,REASONING RATS ,Generalization ,Associative models ,Social Sciences ,HOMO-SAPIENS ,Experimental and Cognitive Psychology ,Rats/physiology ,MATCHING-TO-SAMPLE ,CONNECTIONIST MODEL ,Stimulus (physiology) ,Generalization, Psychological ,Rats sprague dawley ,Discrimination Learning ,Rats, Sprague-Dawley ,Animals ,Humans ,Discrimination learning ,Columbidae/physiology ,Columbidae ,Ecology, Evolution, Behavior and Systematics ,Associative property ,Medicine(all) ,Original Paper ,Communication ,LESIONS ,business.industry ,Generalization (Psychology) ,Association Learning ,Rule-based system ,Rats ,Rule-based ,Pattern Recognition, Visual ,STIMULI ,DISCRIMINATION ,SIMILARITY ,young adult ,Pigeons ,Female ,Artificial intelligence ,business ,Psychology ,RHESUS-MONKEYS - Abstract
Humans can spontaneously create rules that allow them to efficiently generalize what they have learned to novel situations. An enduring question is whether rule-based generalization is uniquely human or whether other animals can also abstract rules and apply them to novel situations. In recent years, there have been a number of high-profile claims that animals such as rats can learn rules. Most of those claims are quite weak because it is possible to demonstrate that simple associative systems (which do not learn rules) can account for the behavior in those tasks. Using a procedure that allows us to clearly distinguish feature-based from rule-based generalization (the Shanks–Darby procedure), we demonstrate that adult humans show rule-based generalization in this task, while generalization in rats and pigeons was based on featural overlap between stimuli. In brief, when learning that a stimulus made of two components (“AB”) predicts a different outcome than its elements (“A” and “B”), people spontaneously abstract an opposites rule and apply it to new stimuli (e.g., knowing that “C” and “D” predict one outcome, they will predict that “CD” predicts the opposite outcome). Rats and pigeons show the reverse behavior—they generalize what they have learned, but on the basis of similarity (e.g., “CD” is similar to “C” and “D”, so the same outcome is predicted for the compound stimulus as for the components). Genuinely rule-based behavior is observed in humans, but not in rats and pigeons, in the current procedure. Electronic supplementary material The online version of this article (doi:10.1007/s10071-015-0895-8) contains supplementary material, which is available to authorized users.
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- 2015
294. Anomalous 14C enrichments in the eastern UK coastal environment
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Muir, Graham K. P., Cook, Gordon T., MacKenzie, Angus B., MacKinnon, Gillian, and Gulliver, Pauline
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QD - Abstract
During the period from 1995 to 2011, 14C measurements from the coast around Hartlepool in NE England have revealed anomalous enrichments in seawater, sediment and marine biota. These cannot be explained on the basis of atomic weapons testing or authorised nuclear industry discharges, including those from the nearby Advanced Gas-cooled Reactor. Enhanced 14C specific activities have also been observed since 2005 in biota during routine monitoring at Hartlepool by the Food Standards Agency, but are reported as ‘likely’ originating from a ‘nearby non-nuclear source’. Studies undertaken in Hartlepool and Teesmouth during 2005 and 2011 suggest that the 14C discharges are in the vicinity of Greatham Creek, with activity levels in biota analogous to those measured at Sellafield, which discharges TBq activities of 14C per annum. However, if the discharges are into Greatham Creek or even the River Tees, it is proposed that they would be much smaller than those at Sellafield and the high specific activities would be due to much smaller dilution factors. The discharge form of the 14C remains unclear. The activity patterns in biota are similar to those at Sellafield, suggesting that initial inputs are dissolved inorganic carbon (DI14C). However, the mussel/seaweed ratios are more akin to those found around Amersham International, Cardiff, which is known to discharge 14C in an organic form. 14C analysis of a sediment core from Seal Sands demonstrated excess 14C to the base of the core (43 – 44 cm). 210Pb dating of the core (0 – 32 cm) produced an accumulation rate of 0.7 g cm-2 y-1, implying that 14C discharges have occurred from the 1960s until the present day.
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- 2015
295. Self-reported childhood maltreatment, lifelong traumatic events and mental disorders in fibromyalgia syndrome: a comparison of US and German outpatients
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Häuser, Winfried, Hoffmann, Eva-Maria, Wolfe, Frederick, Worthing, Angus B., Stahl, Neil, Rothenberg, Russell, and Walitt, Brian
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Adult ,Cross-Cultural Comparison ,Male ,Fibromyalgia ,Emotions ,Anxiety ,Article ,Life Change Events ,Stress Disorders, Post-Traumatic ,Disability Evaluation ,Predictive Value of Tests ,Risk Factors ,Germany ,Outpatients ,Humans ,Child Abuse ,Child ,Pain Measurement ,Cultural Characteristics ,Depression ,Mental Disorders ,Syndrome ,Middle Aged ,United States ,Female ,Self Report ,Stress, Psychological - Abstract
The robustness of findings on retrospective self-reports of childhood maltreatment and lifetime traumatic experiences of adults with fibromyalgia syndrome (FMS) has not been demonstrated by transcultural studies. This is the first transcultural study to focus on the associations between FMS, childhood maltreatment, lifetime psychological traumas, and potential differences between countries adjusting for psychological distress.71 age-and sex-matched US and German FMS outpatients were compared. Childhood maltreatment were assessed by the Childhood Trauma Questionnaire and potential, traumatic experiences by the trauma list of the Munich Composite International Diagnostic Interview. Potential posttraumatic stress disorder (PTSD) was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders IV-TR symptom criteria by the Posttraumatic Diagnostic Scale. Potential depressive and anxiety disorder were assessed by the Patient Health Questionnaire PHQ 4.US and German patients did not significantly differ in the amount of self-reported childhood maltreatment (emotional, physical and sexual abuse or neglect) or in the frequency of lifetime traumatic experiences. No differences in the frequency of potential anxiety, depression, and PTSD were seen. Psychological distress fully accounted for group differences in emotional and sexual abuse and emotional and physical neglect.The study demonstrated the transcultural robustness of findings on the association of adult FMS with self-reports of childhood maltreatment and lifelong traumatic experiences. These associations are mainly explained by current psychological distress.
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- 2015
296. Bone mineral density and inflammatory and bone biomarkers after darunavir-ritonavir combined with either raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults with HIV-1: a substudy of the NEAT001/ANRS143 randomised trial
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Bernardino, J. I., Mocroft, A., Mallon, P. W., Wallet, C., Gerstoft, J., Russell, C., Reiss, P., Katlama, C., De Wit, S., Richert, L., Babiker, A., Buno, A., Castagna, A., Girard, P. -M., Chene, G., Raffi, F., Arribas, J. R., Dedes, N, Chene, G, Richert, L, Allavena, C, Raffi, F, Autran, B, Antinori, A, Bucciardini, R, Vella, S, Horban, A, Arribas, J, Babiker, Ag, Boffito, M, Pillay, D, Pozniak, A, Franquet, X, Schwarze, S, Grarup, J, Fischer, A, Wallet, C, Diallo, A, Molina, Jm, Saillard, J, Moecklinghoff, C, Stellbrink, Hj, Van Leeuwen, R, Gatell, J, Sandstrom, E, Flepp, M, Ewings, F, George, Ec, Hudson, F, Pearce, G, Quercia, R, Rogatto, F, Leavitt, R, Nguyen, By, Goebel, F, Marcotullio, S, Babiker, A, Kaur, N, Sasieni, P, Spencer-Drake, C, Peto, T, Miller, V, Chêne, G, Arnault, F, Boucherie, C, Jean, D, Paniego, V, Paraina, F, Rouch, E, Schwimmer, C, Soussi, M, Taieb, A, Termote, M, Touzeau, G, Cursley, A, Dodds, W, Hoppe, A, Kummeling, I, Pacciarini, F, Paton, N, Russell, C, Taylor, K, Ward, D, Aagaard, B, Eid, M, Gey, D, Jensen, Bg, Jakobsen, Ml, Jansson, Po, Jensen, K, Joensen, Zm, Larsen, Em, Pahl, C, Pearson, M, Nielsen, Br, Reilev, Ss, Christ, I, Lathouwers, D, Mendy, By, Metro, A, Couffin-Cadiergues, S, Knellwolf, Al, Palmisiano, L, Aznar, E, Barea, C, Cotarelo, M, Esteban, H, Girbau, I, Moyano, B, Ramirez, M, Saiz, C, Sanchez, I, Yllescas, M, Binelli, A, Colasanti, V, Massella, M, Anagnostou, O, Gioukari, V, Touloumi, G, Schmied, B, Rieger, A, Vetter, N, De Wit, S, Florence, E, Vandekerckhove, L, Gerstoft, J, Mathiesen, L, Katlama, C, Cabie, A, Cheret, A, Dupon, M, Ghosn, J, Girard, Pm, Goujard, C, Lévy, Y, Morlat, P, Neau, D, Obadia, M, Perre, P, Piroth, L, Reynes, J, Tattevin, P, Ragnaud, Jm, Weiss, L, Yazdan, Y, Yeni, P, Zucman, D, Behrens, G, Esser, S, Fätkenheuer, G, Hoffmann, C, Jessen, H, Rockstroh, J, Schmidt, R, Stephan, C, Unger, S, Hatzakis, A, Daikos, Gl, Papadopoulos, A, Skoutelis, A, Banhegyi, D, Mallon, P, Mulcahy, F, Andreoni, M, Bonora, S, Castelli, F, Monforte, Ad, Di Perri, G, Galli, M, Lazzarin, A, Mazzotta, F, Carlo, T, Vullo, V, Prins, J, Richter, C, Verhagen, D, Van Eeden, A, Doroana, M, Antunes, F, Maltez, F, Sarmento-Castro, R, Gonzalez Garcia, J, López Aldeguer, J, Clotet, B, Domingo, P, Gatell, Jm, Knobel, H, Marquez, M, Pilar Miralles, M, Portilla, J, Soriano, V, Tellez, Mj, Thalme, A, Blaxhult, A, Gisslen, M, Winston, A, Fox, J, Gompels, M, Herieka, E, Johnson, M, Leen, C, Teague, A, Williams, I, Boyd, Ma, Møller, Nf, Frøsig, E, Larsen, M, Le Moing, V, Wit, Fw, Kowalska, J, Berenguer, J, Moreno, S, Müller, Nj, Török, E, Post, F, Angus, B, Calvez, V, Boucher, C, Collins, S, Dunn, D, Lambert, S, Marcelin, Ag, Perno, Cf, White, E, Ammassari, A, Stoehr, W, Schmidt, Re, Odermarsky, M, Smith, C, Thiébaut, R, De La Serna JI, Castagna, A, Furrer, Hj, Mocroft, A, Reiss, P, Fragola, V, Lauriola, M, Murri, R, Nieuwkerk, P, Spire, B, Volny-Anne, A, West, B, Amieva, H, Codina, Jm, Braggion, Marco, Focà, E, Bernardino Jose, I., Mocroft, Amanda, Mallon Patrick, W., Wallet, Cedrick, Gerstoft, Jan, Russell, Charlotte, Reiss, Peter, Katlama, Christine, De Wit, Stephane, Richert, Laura, Babiker, Abdel, Buno, Antonio, Castagna, Antonella, Girard Pierre, Marie, Chene, Genevieve, Raffi, Francoi, Arribas Jose, R., AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, Global Health, Infectious diseases, and Medical Psychology
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Male ,Bone density ,Epidemiology ,Infectious Diseases ,Immunology ,Virology ,Osteoporosis ,HIV Infections ,Comorbidity ,Absorptiometry, Photon ,Bone Density ,Emtricitabine ,Darunavir ,Middle Aged ,Viral Load ,Photon ,Europe ,Osteopetrosis ,Combination ,Drug Therapy, Combination ,Female ,Bone Diseases ,medicine.drug ,Adult ,medicine.medical_specialty ,Anti-HIV Agents ,Biomarkers ,Bone Diseases, Metabolic ,CD4 Lymphocyte Count ,Humans ,Inflammation ,Raltegravir Potassium ,Ritonavir ,Tenofovir ,Tenofovir alafenamide ,Drug Therapy ,Internal medicine ,medicine ,Absorptiometry ,business.industry ,Abacavir/Lamivudine ,Raltegravir ,medicine.disease ,Surgery ,Osteopenia ,Regimen ,Metabolic ,business - Abstract
Osteopenia, osteoporosis, and low bone mineral density are frequent in patients with HIV. We assessed the 96 week loss of bone mineral density associated with a nucleoside or nucleotide reverse transcriptase inhibitor (NtRTI)-sparing regimen. Antiretroviral-naive adults with HIV were enrolled in 78 clinical sites in 15 European countries into a randomised (1:1), open-label, non-inferiority trial (NEAT001/ANRS143) assessing the efficacy and safety of darunavir (800 mg once per day) and ritonavir (100 mg once per day) plus either raltegravir (400 mg twice per day; NtRTI-sparing regimen) or tenofovir (245 mg once per day) and emtricitabine (200 mg once per day; standard regimen). For this bone-health substudy, 20 of the original sites in six countries participated, and any patient enrolled at one of these sites who met the following criteria was eligible: plasma viral loads greater than 1000 HIV RNA copies per mL and CD4 cell counts of fewer than 500 cells per μL, except in those with symptomatic HIV infection. Exclusion criteria included treatment for malignant disease, testing positive for hepatitis B virus surface antigen, pregnancy, creatinine clearance less than 60 mL per min, treatment for osteoporosis, systemic steroids, or oestrogen-replacement therapy. The two primary endpoints were the mean percentage changes in lumbar spine and total hip bone mineral density at week 48, assessed by dual energy x-ray absorptiometry (DXA) scans. We did the analysis with an intention-to-treat-exposed approach with antiretroviral modifications ignored. The parent trial is registered with ClinicalTrials.gov, number NCT01066962, and is closed to new participants. Between Aug 2, 2010, and April 18, 2011, we recruited 146 patients to the substudy, 70 assigned to the NtRTI-sparing regimen and 76 to the standard regimen. DXA data were available for 129, 121 and 107 patients at baseline, 48 and 96 weeks respectively. At week 48, the mean percentage loss in bone mineral density in the lumbar spine was greater in the standard group than in the NtRTI-sparing group (mean percentage change -2.49% vs -1.00%, mean percentage difference -1.49, 95% CI -2.94 to -0.04; p=0.046). Total hip bone mineral density loss was similarly greater at week 48 in the standard group than in the NtRTI-sparing group (mean percentage change -3.30% vs -0.73%; mean percentage difference -2.57, 95% CI -3.75 to -1.35; p
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- 2015
297. Manmade and natural radionuclides in north east Atlantic shelf and slope sediments: Implications for rates of sedimentary processes and for contaminant dispersion
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D J Ellet, A Stewart, L Mitchell, Gordon Cook, Angus B. MacKenzie, and Colin Griffiths
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Radioactive Fallout ,Radioisotopes ,Geologic Sediments ,Water Pollutants, Radioactive ,geography ,Environmental Engineering ,geography.geographical_feature_category ,Continental shelf ,Sediment ,Context (language use) ,Sedimentation ,Pollution ,Oceanography ,Radioactive Waste ,Environmental Chemistry ,Seawater ,Sedimentary rock ,Atlantic Ocean ,Waste Management and Disposal ,Holocene ,Geology ,Environmental Monitoring ,Nuclear Warfare - Abstract
Results are presented for a study of manmade and natural radionuclides in north east Atlantic continental shelf and slope sediments to the west of Scotland. The data are interpreted in the context of sediment mixing and accumulation processes and are used to establish the westward extent of contamination of the sediment system. Offshore shelf and slope sediments were found to have post-glacial sedimentation rates of the order of 1 cm ky(-1) but nearshore sediments had much higher accumulation rates of the order of 0.1 cm y(-1). Surface mixed layer depths of up to 6 cm were observed and non-local mixing affected most of the slope sediments, resulting in advective transport of surface sediment to depths of up to 10 cm. Biodiffusion coefficients for offshore shelf and slope sediments were dominantly in the range 10(-8) to 10(-9) cm2 s(-1). The study confirmed that seawater contaminated with Sellafield waste radionuclides is dominantly entrained to the east of 7 degrees W and, consistent with this, higher levels of Sellafield derived radionuclides were confined to nearshore sediments, with lower levels to the west of 7 degrees W. 238Pu/(239,240)Pu data indicated that Sellafield contributed 75-91% of the total plutonium in coastal sediment but only about 4-8% of the total in slope sediments. By analogy, it can be concluded that a similar situation will apply to other contaminants in seawater entering the north east Atlantic via the North Channel.
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- 2006
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298. Use of 206Pb/207Pb ratios to investigate the surface integrity of peat cores used to study the recent depositional history and geochemical behaviour of inorganic elements in peat bogs
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C. Yafa, Angus B. MacKenzie, John G. Farmer, Margaret C. Graham, A. J. Freeman, and Joanna M. Cloy
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Global and Planetary Change ,Radionuclide ,geography ,Peat ,geography.geographical_feature_category ,Phosphorus ,chemistry.chemical_element ,Ombrotrophic ,Soil science ,Oceanography ,Coring ,Sedimentary depositional environment ,Deposition (aerosol physics) ,chemistry ,Mining engineering ,Bog ,Geology - Abstract
The well characterised temporal trend in the 206 Pb/ 207 Pb atom ratio of atmospheric lead deposition in Scotland during the 20th century was used to investigate the surface integrity of several cores collected by different methods from Flanders Moss ombrotrophic peat bog, central Scotland, during 1996–2001. Based on 206 Pb/ 207 Pb profile comparisons, in conjunction with identified 210 Pb radionuclide inventory deficits for two of the cores, it was deduced that 25 ± 7 yrs worth of material was missing from the more seriously affected core. After allowing for an appropriate vertical offset based on 206 Pb/ 207 Pb profile matching, the subsequent matching of profiles of titanium, lead, sulfur, arsenic, iron, phosphorus and manganese in three cores for which total concentration data were available was excellent. Without such offset correction, erroneous conclusions could have been drawn concerning the recent historical record of anthropogenic lead and arsenic deposition, the position of the redox boundary, which controls geochemical cycling and enrichment of iron, and the nutrient recycling status of manganese and phosphorus in the near-surface vegetation. Topographic, vegetative and coring (both device and operator) influences may have been responsible, thus endorsing the use of reliable, multiple core sampling and the use of lead isotope ratio profiles, supplemented by appropriate radionuclide data, in both assessing and ensuring the surface integrity of peat cores.
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- 2006
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299. An overview of a natural analogue study of the Tono Uranium Deposit, central Japan
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Randolph C. Arthur, Eiji Sasao, Angus B. MacKenzie, Michael J. Stenhouse, Kunio Ota, Tadafumi Niizato, Hiroyasu Takase, Richard Metcalfe, Wei Zhou, and Teruki Iwatsuki
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geography ,geography.geographical_feature_category ,Human environment ,Hydrogeology ,Geochemistry ,Radioactive waste ,General Chemistry ,Numerical models ,Fault (geology) ,Natural (archaeology) ,Geological Phenomena ,Mining engineering ,Geochemistry and Petrology ,General Earth and Planetary Sciences ,Geology ,General Environmental Science ,Uranium deposit - Abstract
The basic concept of deep geological disposal of high-level radioactive waste is to isolate the waste from the human environment for the long term. Because the Japanese islands are located in a geologically active area, geological phenomena such as exhumation and fault activity must be considered by any safety assessment connected with deep geological disposal. The Tono Uranium Deposit, central Japan, has been affected by such geological phenomena during the interval since its formation, and so it is a suitable analogue for evaluating how this might be done. The present natural analogue study of the Tono Uranium Deposit (Tono Natural Analogue Project) was started in 2001 with the main aim of studying a so-called ‘worst-case scenario’ for performance assessment (PA). The project involved characterizing the geology, hydrogeology, geochemistry and microbiology of the deposit and obtaining quantitative information about specific times in the past, as a means for developing, and building confidence in, conceptual and numerical models. This project applied systems analysis, which has been widely undertaken in PAs of deep geological isolation. Systems analysis involves a systematic identification, classification and screening of features, events and process (FEPs) that occur or have occurred in and around the deposit. Based on the site data, important FEPs were identified.
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- 2006
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300. A system model for the origin and evolution of the Tono Uranium Deposit, Japan
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Hiroyasu Takase, Michael J. Stenhouse, Richard Metcalfe, Randolph C. Arthur, Kunio Ota, Angus B. MacKenzie, Eiji Sasao, Teruki Iwatsuki, and Wei Zhou
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Geochemistry ,chemistry.chemical_element ,Radioactive waste ,Subsidence ,General Chemistry ,Uranium ,Deposition (geology) ,chemistry ,Geochemistry and Petrology ,Genetic model ,General Earth and Planetary Sciences ,Sedimentary rock ,Precipitation ,Geology ,Groundwater ,General Environmental Science - Abstract
Data from the Tono Uranium Deposit of central Japan were used to develop an improved approach for simulating uranium migration and retardation, while taking into account both long-term environmental changes and uncertainties in data. Based upon extensive field and laboratory investigations, conceptual and numerical models for environmental perturbations, including uplift, subsidence and faulting, were constructed. Model development was based on a novel adaptation of a safety assessment methodology that previously has been applied to radioactive waste repositories. A ‘reference scenario’ was developed using a systems analysis approach. This scenario is a best estimate of how the geological system and the uranium deposit reached their present states and includes descriptions of all major environmental perturbations. Uranium is mobilized from the uppermost Toki granite under relatively oxidizing conditions, and is then transported by groundwater into overlying sedimentary rocks. There, reducing conditions promote uranium deposition. A specially designed numerical model simulated the main features of this scenario. Many simulations were performed to identify key uncertainties to which the timing of ore deposition and uranium distribution are sensitive. A key finding is that retardation of U by processes other than precipitation of discrete U minerals, most probably sorption on solid phases, contributes significantly to the stability of the ore deposit. Sorption could potentially be important for confining the U within the sedimentary rocks in spite of environmental changes such as exhumation and seismic pumping. The approach could be used elsewhere, to assess the safety of deep geological high-level radioactive waste (HLW) disposal. A related application would be at potential future waste disposal sites, to prioritize site characterization so that the most safety-relevant uncertainties are reduced. There are also possible applications in other fields, most notably to assess the implications of alternative ore genetic models.
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- 2006
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