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368 results on '"Mazur, J."'

3. Development And In Vitro Characterization Of Bladder Tumor Cell Targeted Lipid-Coated Polyplex For Dual Delivery Of Plasmids And Small Molecules

Author

Samaddar S, Mazur J, Boehm D, and Thompson DH

Subjects
dual delivery, bladder cancer, gene therapy, Medicine (General), R5-920
Abstract

Shayak Samaddar, Joshua Mazur, Devin Boehm, David H Thompson Department of Chemistry, Purdue University, Bindley Bioscience Center, West Lafayette, Indiana 47906, USACorrespondence: David H ThompsonDepartment of Chemistry, Purdue University, Bindley Bioscience Center, 1203 W. State St., West Lafayette, Indiana 47906, USATel +1 765-494-0386Email davethom@purdue.eduBackground: Bladder cancer is the fourth most common cancer in men and eleventh most common in women. Combination therapy using a gene and chemotherapeutic drug is a potentially useful strategy for treating bladder cancer in cases where a synergistic benefit can be achieved successfully. This approach relies on developing drug combinations using carrier systems that can load both hydrophilic genes and hydrophobic drugs. Ideally, the formulation for carrier system should be free of traditional high shear techniques such as sonication and extrusion to reduce shear-induced nucleic acid strand breakage. Moreover, the system should be able to protect the nucleic acid from enzymatic attack and deliver it specifically to the tumor site.Materials and methods: A dual payload carrier system that was formulated using a simple flow mixing technique to complex anionic plasmid (EGFP-NLS) using a cationic polymer (CD-PEI2.5kD) followed by coating of the polyplex using lipid membranes. The resulting lipid-coated polyplex (LCP) formulations are targeted to bladder cancer cells by employing a bacterial adhesive peptide sequence, RWFV, that targets the LCP to the tumor stroma for efficiently delivering reporter plasmid, EGFP-NLS and a model small molecule drug, pyrene, to the cancer cells.Results: Encapsulation efficiency of the peptide targeted carrier for the plasmid was 50% ± 0.4% and for pyrene it was 16% ± 0.4%. The ability of the targeted LCP to transfect murine bladder cancer cells was 4-fold higher than LCP bearing a scrambled peptide sequence. Fluorescence of cells due to pyrene delivery was highest after 4 hrs using targeted LCP. Finally, we loaded the peptide targeted LCP with anti-cancer agent, curcumin. The targeted formulation of curcumin resulted in only 45% viable cancer cells at a concentration of 5 μg/mL, whereas the empty and non-targeted formulations did not result any significant cell death.Conclusion: These results demonstrate the specificity of the targeting peptide sequence in engaging tumor cells and the utility of the developed carrier platform to deliver a dual payload to bladder tumor cells.Keywords: dual delivery, bladder cancer, gene therapy

Published
2019

9. The relationship between uremic toxins and symptoms in older men and women with advanced chronic kidney disease

Author

Massy Z. A., Chesnaye N. C., Larabi I. A., Dekker F. W., Evans M., Caskey F. J., Torino C., Porto G., Szymczak M., Drechsler C., Wanner C., Jager K. J., Alvarez J. C., Schneider A., Torp A., Iwig B., Perras B., Marx C., Blaser C., Emde C., Krieter D., Fuchs D., Irmler E., Platen E., Schmidt-Gurtler H., Schlee H., Naujoks H., Schlee I., Casar S., Beige J., Rothele J., Mazur J., Hahn K., Blouin K., Neumeier K., Anding-Rost K., Schramm L., Hopf M., Wuttke N., Frischmuth N., Ichtiaris P., Kirste P., Schulz P., Aign S., Biribauer S., Manan S., Roser S., Heidenreich S., Palm S., Schwedler S., Delrieux S., Renker S., Schattel S., Stephan T., Schmiedeke T., Weinreich T., Leimbach T., Stovesand T., Bahner U., Seeger W., Cupisti A., Sagliocca A., Ferraro A., Mele A., Naticchia A., Cosaro A., Ranghino A., Stucchi A., Pignataro A., De Blasio A., Pani A., Tsalouichos A., Bellasi A., Raffaele Di Iorio B., Butti A., Abaterusso C., Somma C., D'Alessandro C., Zullo C., Pozzi C., Bergamo D., Ciurlino D., Motta D., Russo D., Favaro E., Vigotti F., Ansali F., Conte F., Cianciotta F., Giacchino F., Cappellaio F., Pizzarelli F., Greco G., Bigatti G., Marinangeli G., Cabiddu G., Fumagalli G., Caloro G., Piccoli G., Capasso G., Gambaro G., Tognarelli G., Bonforte G., Conte G., Toscano G., Del Rosso G., Capizzi I., Baragetti I., Oldrizzi L., Gesualdo L., Biancone L., Magnano M., Ricardi M., Di Bari M., Laudato M., Luisa Sirico M., Ferraresi M., Provenzano M., Malaguti M., Palmieri N., Murrone P., Cirillo P., Dattolo P., Acampora P., Nigro R., Boero R., Scarpioni R., Sicoli R., Malandra R., Savoldi S., Bertoli S., Borrelli S., Maxia S., Maffei S., Mangano S., Cicchetti T., Rappa T., Palazzo V., De Simone W., Schrander A., Van Dam B., Siegert C., Gaillard C., Beerenhout C., Verburgh C., Janmaat C., Hoogeveen E., Hoorn E., Boots J., Boom H., Eijgenraam J. -W., Kooman J., Rotmans J., Vogt L., Raasveld M., Vervloet M., Van Buren M., Van Diepen M., Leurs P., Voskamp P., Blankestijn P., Van Esch S., Boorsma S., Berger S., Konings C., Aydin Z., Musiala A., Szymczak A., Olczyk E., Augustyniak-Bartosik H., Miskowiec-Wisniewska I., Manitius J., Pondel J., Jedrzejak K., Nowanska K., Nowak L., Durlik M., Dorota S., Nieszporek T., Heleniak Z., Jonsson A., Blom A. -L., Rogland B., Wallquist C., Vargas D., Dimeny E., Sundelin F., Uhlin F., Welander G., Bascaran Hernandez I., Grontoft K. -C., Stendahl M., Svensson M., Heimburger O., Kashioulis P., Melander S., Almquist T., Jensen U., Woodman A., McKeever A., Ullah A., McLaren B., Harron C., Barrett C., O'Toole C., Summersgill C., Geddes C., Glowski D., McGlynn D., Sands D., Roy G., Hirst G., King H., McNally H., Masri-Senghor H., Murtagh H., Rayner H., Turner J., Wilcox J., Berdeprado J., Wong J., Banda J., Jones K., Haydock L., Wilkinson L., Carmody M., Weetman M., Joinson M., Dutton M., Matthews M., Morgan N., Bleakley N., Cockwell P., Roderick P., Mason P., Kalra P., Sajith R., Chapman S., Navjee S., Crosbie S., Brown S., Tickle S., Mathavakkannan S., Kuan Y., Massy, Z. A., Chesnaye, N. C., Larabi, I. A., Dekker, F. W., Evans, M., Caskey, F. J., Torino, C., Porto, G., Szymczak, M., Drechsler, C., Wanner, C., Jager, K. J., Alvarez, J. C., Schneider, A., Torp, A., Iwig, B., Perras, B., Marx, C., Blaser, C., Emde, C., Krieter, D., Fuchs, D., Irmler, E., Platen, E., Schmidt-Gurtler, H., Schlee, H., Naujoks, H., Schlee, I., Casar, S., Beige, J., Rothele, J., Mazur, J., Hahn, K., Blouin, K., Neumeier, K., Anding-Rost, K., Schramm, L., Hopf, M., Wuttke, N., Frischmuth, N., Ichtiaris, P., Kirste, P., Schulz, P., Aign, S., Biribauer, S., Manan, S., Roser, S., Heidenreich, S., Palm, S., Schwedler, S., Delrieux, S., Renker, S., Schattel, S., Stephan, T., Schmiedeke, T., Weinreich, T., Leimbach, T., Stovesand, T., Bahner, U., Seeger, W., Cupisti, A., Sagliocca, A., Ferraro, A., Mele, A., Naticchia, A., Cosaro, A., Ranghino, A., Stucchi, A., Pignataro, A., De Blasio, A., Pani, A., Tsalouichos, A., Bellasi, A., Raffaele Di Iorio, B., Butti, A., Abaterusso, C., Somma, C., D'Alessandro, C., Zullo, C., Pozzi, C., Bergamo, D., Ciurlino, D., Motta, D., Russo, D., Favaro, E., Vigotti, F., Ansali, F., Conte, F., Cianciotta, F., Giacchino, F., Cappellaio, F., Pizzarelli, F., Greco, G., Bigatti, G., Marinangeli, G., Cabiddu, G., Fumagalli, G., Caloro, G., Piccoli, G., Capasso, G., Gambaro, G., Tognarelli, G., Bonforte, G., Conte, G., Toscano, G., Del Rosso, G., Capizzi, I., Baragetti, I., Oldrizzi, L., Gesualdo, L., Biancone, L., Magnano, M., Ricardi, M., Di Bari, M., Laudato, M., Luisa Sirico, M., Ferraresi, M., Provenzano, M., Malaguti, M., Palmieri, N., Murrone, P., Cirillo, P., Dattolo, P., Acampora, P., Nigro, R., Boero, R., Scarpioni, R., Sicoli, R., Malandra, R., Savoldi, S., Bertoli, S., Borrelli, S., Maxia, S., Maffei, S., Mangano, S., Cicchetti, T., Rappa, T., Palazzo, V., De Simone, W., Schrander, A., Van Dam, B., Siegert, C., Gaillard, C., Beerenhout, C., Verburgh, C., Janmaat, C., Hoogeveen, E., Hoorn, E., Boots, J., Boom, H., Eijgenraam, J. -W., Kooman, J., Rotmans, J., Vogt, L., Raasveld, M., Vervloet, M., Van Buren, M., Van Diepen, M., Leurs, P., Voskamp, P., Blankestijn, P., Van Esch, S., Boorsma, S., Berger, S., Konings, C., Aydin, Z., Musiala, A., Szymczak, A., Olczyk, E., Augustyniak-Bartosik, H., Miskowiec-Wisniewska, I., Manitius, J., Pondel, J., Jedrzejak, K., Nowanska, K., Nowak, L., Durlik, M., Dorota, S., Nieszporek, T., Heleniak, Z., Jonsson, A., Blom, A. -L., Rogland, B., Wallquist, C., Vargas, D., Dimeny, E., Sundelin, F., Uhlin, F., Welander, G., Bascaran Hernandez, I., Grontoft, K. -C., Stendahl, M., Svensson, M., Heimburger, O., Kashioulis, P., Melander, S., Almquist, T., Jensen, U., Woodman, A., Mckeever, A., Ullah, A., Mclaren, B., Harron, C., Barrett, C., O'Toole, C., Summersgill, C., Geddes, C., Glowski, D., Mcglynn, D., Sands, D., Roy, G., Hirst, G., King, H., Mcnally, H., Masri-Senghor, H., Murtagh, H., Rayner, H., Turner, J., Wilcox, J., Berdeprado, J., Wong, J., Banda, J., Jones, K., Haydock, L., Wilkinson, L., Carmody, M., Weetman, M., Joinson, M., Dutton, M., Matthews, M., Morgan, N., Bleakley, N., Cockwell, P., Roderick, P., Mason, P., Kalra, P., Sajith, R., Chapman, S., Navjee, S., Crosbie, S., Brown, S., Tickle, S., Mathavakkannan, S., Kuan, Y., Nephrology, ACS - Diabetes & metabolism, Medical Informatics, APH - Methodology, APH - Aging & Later Life, APH - Quality of Care, APH - Global Health, APH - Health Behaviors & Chronic Diseases, and ACS - Pulmonary hypertension & thrombosis

Subjects
Transplantation, Nephrology, uremic toxins, CKD, symptoms, symptom, elderly
Abstract

Background Patients with stage 4/5 chronic kidney disease (CKD) suffer from various symptoms. The retention of uremic solutes is thought to be associated with those symptoms. However, there are relatively few rigorous studies on the potential links between uremic toxins and symptoms in patients with CKD. Methods The EQUAL study is an ongoing observational cohort study of non-dialyzed patients with stage 4/5 CKD. EQUAL patients from Germany, Poland, Sweden and the UK were included in the present study (n = 795). Data and symptom self-report questionnaires were collected between April 2012 and September 2020. Baseline uric acid and parathyroid hormone and 10 uremic toxins were quantified. We tested the association between uremic toxins and symptoms and adjusted P-values for multiple testing. Results Symptoms were more frequent in women than in men with stage 4/5 CKD, while levels of various uremic toxins were higher in men. Only trimethylamine N-oxide (TMAO; positive association with fatigue), p-cresyl sulfate (PCS) with constipation and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (negative association with shortness of breath) demonstrated moderately strong associations with symptoms in adjusted analyses. The association of phenylacetylglutamine with shortness of breath was consistent in both sexes, although it only reached statistical significance in the full population. In contrast, TMAO (fatigue) and PCS and phenylacetylglutamine (constipation) were only associated with symptoms in men, who presented higher serum levels than women. Conclusion Only a limited number of toxins were associated with symptoms in persons with stage 4/5 CKD. Other uremic toxins, uremia-related factors or psychosocial factors not yet explored might contribute to symptom burden.

Published
2022

12. Signatures of volatiles in the lunar proton albedo

Author

Schwadron, N.A., Wilson, J.K., Looper, M.D., Jordan, A.P., Spence, H.E., Blake, J.B., Case, A.W., Iwata, Y., Kasper, J.C., Farrell, W.M., Lawrence, D.J., Livadiotis, G., Mazur, J., Petro, N., Pieters, C., Robinson, M.S., Smith, S., Townsend, L.W., and Zeitlin, C.

Published
2016
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13. Fabrication And Properties Of Silver Based Multiwall Carbon Nanotube Composite Prepared By Spark Plasma Sintering Method

Author

Lis M., Wrona A., Mazur J., Dupont C., Kamińska M., Kopyto D., and Kwarciński M.

Subjects
Spark Plasma Sintering, Composites, Ag - Carbon Nanotubes, Dispersion, Microstructure, Mining engineering. Metallurgy, TN1-997, Materials of engineering and construction. Mechanics of materials, TA401-492
Abstract

The paper presents results of investigations of the obtained nanocomposite materials based on silver with addition of multiwall carbon nanotubes. The powder of carbon nanotubes content from 0.1 to 3 wt. % was produced by application of powder metallurgy methods, through mixing and high-energetic milling, and also chemical methods. Modification of carbon nanotubes included electroless deposition of silver particles on the carbon nanotube active surfaces and chemical reduction with strong reducing agent – sodium borohydride (NaBH4). The obtained powder mixtures were consolidated by SPS – Spark Plasma Sintering method. The formed composites were subjected to tests of relative density, electrical conductivity and electro-erosion properties. Detailed examinations of the structure with application of X-ray microanalysis, with consideration of carbon nanotubes distribution, were also carried out. The effect of manufacturing methods on properties of the obtained composites was observed.

Published
2015
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14. Indoor radon exposure and living conditions in patients with advanced lung cancer in Lublin region, Poland.

Author

GRZYWA-CELIŃSKA, A., KRUSIŃSKI, A., KOZAK, K., MAZUR, J., GRZĄDZIEL, D., SANTOS SZEWCZYK, K. DOS, CHMIELEWSKA, I., and MILANOWSKI, J.

Abstract

OBJECTIVE: Radon (Rn-222) is a noble gas formed in the uranium path (U-238) as a decay product of radium (Ra-226). It is estimated to cause between 3% to 14% of all lung cancers, depending on the national average radon level and smoking prevalence. Radon molecules emit alpha radiation, which is characterized by low permeability through tissues, but due to its remarkably high energy, it has a high potential for DNA damage. The aim of our research was to assess the radon concentration inside the houses of patients with advanced lung cancer and to analyze their socio-economics status. PATIENTS AND METHODS: The measurements of radon concentration were performed in 102 patients with stage 3B or higher lung cancer in the region of Lublin, Poland. One month of radon exposure measurement was performed with alpha-track detectors. In addition, patients filled in a detailed survey about factors that might influence the concentration of radon inside their houses. RESULTS: The average concentration of radon during the exposure of the detector in the residential premises of the respondents was at the level of 69.0 Bq/m3 [37.0-117.0]. A few significant correlations were discovered, e.g., higher levels of radon in countryside houses or in houses equipped with air conditioning. CONCLUSIONS: As radon exposure is a modifiable risk factor for lung cancer, it is extremely important to find factors that may reduce its concentration in dwelling places. Since our research was performed in houses of people with lung cancer, taking corrective actions based on our findings could prevent new lung cancer incidence in patients' flatmates. [ABSTRACT FROM AUTHOR]

Published
2023

16. SAMPEX Observations of the South Atlantic Anomaly Secular Drift During Solar Cycles 22-24

Author

Jones, A. D, Kanekal, S. G, Baker, D. N, Klecker, B, Looper, M.D, Mazur, J. E, and Schiller, Q

Subjects
Geophysics
Abstract

It is observed that charged particle intensities are very high near the South Atlantic anomaly (SAA) and are a potential hazard to spacecraft passing through the region. In this study, we examine the secular drift of the SAA location at approximately 400-600 kilometers altitude over nearly two solar cycles, using particle count rates to trace the geomagnetic field lines in the region near the SAA. We use data from the Low-Energy Ion Composition Analyzer sensor on board the SAMPEX (Solar, Anomalous, and Magnetospheric Particle Explorer) spacecraft to measure both the longitudinal and latitudinal drifts of the SAA. We find that the longitudinal drift rate is 0.20 plus or minus 0.04 degrees west per year and that the latitudinal drift rate is 0.11 plus or minus 0.01 degrees south per year. These measurements are compared with the IGRF12 (International Geomagnetic Reference Field) model calculations based on an analysis of magnetic field minima in the region of the SAA. Our results, which are in good agreement with model results and prior measurements when declining spacecraft altitude is taken into account, have important space weather implications.

Published
2017
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18. Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial

Author

Ray, K, Colhoun, H, Szarek, M, Baccara-Dinet, M, Bhatt, D, Bittner, V, Budaj, A, Diaz, R, Goodman, S, Hanotin, C, Harrington, R, Jukema, J, Loizeau, V, Lopes, R, Moryusef, A, Murin, J, Pordy, R, Ristic, A, Roe, M, Tunon, J, White, H, Zeiher, A, Schwartz, G, Steg, P, Tricoci, P, Mahaffey, K, Edelberg, J, Lecorps, G, Sasiela, W, Tamby, J, Aylward, P, Drexel, H, Sinnaeve, P, Dilic, M, Gotcheva, N, Prieto, J, Yong, H, Lopez-Jaramillo, P, Pecin, I, Reiner, Z, Ostadal, P, Viigimaa, M, Nieminen, M, Chumburidze, V, Marx, N, Danchin, N, Liberopoulos, E, Montenegro Valdovinos, P, Tse, H, Kiss, R, Xavier, D, Zahger, D, Valgimigli, M, Kimura, T, Kim, H, Kim, S, Erglis, A, Laucevicius, A, Kedev, S, Yusoff, K, Ramos Lopez, G, Alings, M, Halvorsen, S, Correa Flores, R, Morais, J, Dorobantu, M, Karpov, Y, Chua, T, Fras, Z, Dalby, A, de Silva, H, Hagstrom, E, Landmesser, U, Chiang, C, Sritara, P, Guneri, S, Parkhomenko, A, Moriarty, P, Vogel, R, Chaitman, B, Kelsey, S, Olsson, A, Rouleau, J, Simoons, M, Alexander, K, Meloni, C, Rosenson, R, Sijbrands, E, Alexander, J, Armaganijan, L, Bagai, A, Bahit, M, Brennan, J, Clifton, S, Devore, A, Deloatch, S, Dickey, S, Dombrowski, K, Ducrocq, G, Eapen, Z, Endsley, P, Eppinger, A, Harrison, R, Hess, C, Hlatky, M, Jordan, J, Knowles, J, Kolls, B, Kong, D, Leonardi, S, Lillis, L, Maron, D, Marcus, J, Mathews, R, Mehta, R, Mentz, R, Moreira, H, Patel, C, Bernardez-Pereira, S, Perkins, L, Povsic, T, Puymirat, E, Schuyler Jones, W, Shah, B, Sherwood, M, Stringfellow, K, Sujjavanich, D, Toma, M, Trotter, C, Van Diepen, S, Wilson, M, Yan, A, Schiavi, L, Garrido, M, Alvarisqueta, A, Sassone, S, Bordonava, A, Alves De Lima, A, Schmidberg, J, Duronto, E, Caruso, O, Novaretto, L, Hominal, M, Montana, O, Caccavo, A, Gomez Vilamajo, O, Lorenzatti, A, Cartasegna, L, Paterlini, G, Mackinnon, I, Caime, G, Amuchastegui, M, Salomone, O, Codutti, O, Jure, H, Bono, J, Hrabar, A, Vallejos, J, Ahuad Guerrero, R, Novoa, F, Patocchi, C, Zaidman, C, Giuliano, M, Dran, R, Vico, M, Carnero, G, Guzman, P, Medrano Allende, J, Garcia Brasca, D, Bustamante Labarta, M, Nani, S, Blumberg, E, Colombo, H, Liberman, A, Fuentealba, V, Luciardi, H, Waisman, G, Berli, M, Garcia Duran, R, Cestari, H, Luquez, H, Giordano, J, Saavedra, S, Zapata, G, Costamagna, O, Llois, S, Waites, J, Collins, N, Soward, A, Hii, C, Shaw, J, Arstall, M, Horowitz, J, Ninio, D, Rogers, J, Colquhoun, D, Oqueli Flores, R, Roberts-Thomson, P, Raffel, O, Lehman, S, Aroney, C, Coverdale, S, Garrahy, P, Starmer, G, Sader, M, Carroll, P, Dick, R, Zweiker, R, Hoppe, U, Huber, K, Berger, R, Delle-Karth, G, Frey, B, Weidinger, F, Faes, D, Hermans, K, Pirenne, B, Leone, A, Hoffer, E, Vrolix, M, De Wolf, L, Wollaert, B, Castadot, M, Dujardin, K, Beauloye, C, Vervoort, G, Striekwold, H, Convens, C, Roosen, J, Barbato, E, Claeys, M, Cools, F, Terzic, I, Barakovic, F, Midzic, Z, Pojskic, B, Fazlibegovic, E, Kulic, M, Durak-Nalbantic, A, Vulic, D, Muslibegovic, A, Goronja, B, Reis, G, Sousa, L, Nicolau, J, Giorgeto, F, Silva, R, Nigro Maia, L, Rech, R, Rossi, P, Cerqueira, M, Duda, N, Kalil, R, Kormann, A, Abrantes, J, Pimentel Filho, P, Soggia, A, de Santos, M, Neuenschwander, F, Bodanese, L, Michalaros, Y, Eliaschewitz, F, Vidotti, M, Leaes, P, Botelho, R, Kaiser, S, Manenti, E, Precoma, D, Moura Jorge, J, de B Silva, P, Silveira, J, Saporito, W, Marin-Neto, J, Feitosa, G, Ritt, L, de Souza, J, Costa, F, Souza, W, Reis, H, Machado, L, Ayoub, J, Todorov, G, Nikolov, F, Velcheva, E, Tzekova, M, Benov, H, Petranov, S, Tumbev, H, Shehova-Yankova, N, Markov, D, Raev, D, Mollov, M, Kichukov, K, Ilieva-Pandeva, K, Ivanova, R, Gospodinov, M, Mincheva, V, Lazov, P, Dimov, B, Senaratne, M, Stone, J, Kornder, J, Pearce, S, Dion, D, Savard, D, Pesant, Y, Pandey, A, Robinson, S, Gosselin, G, Vizel, S, Hoag, G, Bourgeois, R, Morisset, A, Sabbah, E, Sussex, B, Kouz, S, Macdonald, P, Diaz, A, Michaud, N, Fell, D, Leung, R, Vuurmans, T, Lai, C, Nigro, F, Davies, R, Nogareda, G, Vijayaraghavan, R, Ducas, J, Lepage, S, Mehta, S, Cha, J, Dupuis, R, Fong, P, Lutchmedial, S, Rodes-Cabau, J, Fadlallah, H, Cleveland, D, Huynh, T, Bata, I, Hameed, A, Pincetti, C, Potthoff, S, Acevedo, M, Aguirre, A, Vejar, M, Yanez, M, Araneda, G, Fernandez, M, Perez, L, Varleta, P, Florenzano, F, Huidobro, L, Raffo, C, Olivares, C, Nahuelpan, L, Montecinos, H, Chen, J, Dong, Y, Huang, W, Wang, J, Huang, S, Yao, Z, Li, X, Cui, L, Lin, W, Sun, Y, Li, J, Zhang, X, Zhu, H, Chen, D, Huang, L, Dong, S, Su, G, Xu, B, Su, X, Cheng, X, Lin, J, Zong, W, Li, H, Feng, Y, Xu, D, Yang, X, Ke, Y, Lin, X, Zhang, Z, Zheng, Z, Luo, Z, Chen, Y, Ding, C, Zhong, Y, Zheng, Y, Peng, D, Zhao, S, Li, Y, Liu, X, Wei, M, Liu, S, Yu, Y, Qu, B, Jiang, W, Zhou, Y, Zhao, X, Yuan, Z, Guo, Y, Xu, X, Shi, X, Ge, J, Fu, G, Bai, F, Fang, W, Shou, X, Xiang, M, Lu, Q, Zhang, R, Zhu, J, Xu, Y, Fan, Z, Li, T, Wu, C, Jaramillo, N, Sanchez Vallejo, G, Luna Botia, D, Botero Lopez, R, Molina De Salazar, D, Cadena Bonfanti, A, Cotes Aroca, C, Diego Higuera, J, Blanquicett, M, Barrera Silva, S, Garcia Lozada, H, Coronel Arroyo, J, Accini Mendoza, J, Fernandez Ruiz, R, Quintero Ossa, A, Manzur Jatin, F, Sotomayor Herazo, A, Castellanos Parada, J, Suarez Arambula, R, Urina Triana, M, Fernandez Trujillo, A, Strozzi, M, Car, S, Jeric, M, Milicic, D, Bencic, M, Pintaric, H, Prvulovic, D, Sikic, J, Persic, V, Mileta, D, Stambuk, K, Babic, Z, Tomulic, V, Lukenda, J, Mejic-Krstulovic, S, Starcevic, B, Spinar, J, Horak, D, Velicka, Z, Stasek, J, Alan, D, Machova, V, Linhart, A, Novotny, V, Kaucak, V, Rokyta, R, Naplava, R, Coufal, Z, Adamkova, V, Podpera, I, Zizka, J, Motovska, Z, Marusincova, I, Svab, P, Heinc, P, Kuchar, J, Povolny, P, Matuska, J, Poulsen, S, Raungaard, B, Clemmensen, P, Bang, L, May, O, Bottcher, M, Hove, J, Frost, L, Gislason, G, Larsen, J, Betton Johansen, P, Hald, F, Johansen, P, Jeppesen, J, Nielsen, T, Kristensen, K, Walichiewicz, P, Lomholdt, J, Klausen, I, Nielsen, P, Davidsen, F, Videbaek, 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S., Kumkumian G., Lupovitch S., Purow J., Welka S., Hoffman D., Fischer S., Soroka E., Eagerton D., Pancholy S., Ray M., Erenrich N., Farrar M., Pollock S., French W. J., Diamantis S., Guy D., Gimple L., Neustel M., Schwartz S., Pereira E., Albert S., Spriggs D., Strain J., Mittal S., Vo A., Chane M., Hall J., Vijay N., Lotun K., Lester F. M., Nahhas A., Pope T., Nager P., Vohra R., Sharma M., Bashir R., Ahmed H., Berlowitz M., Fishberg R., Barrucco R., Yang E., Radin M., Sporn D., Stapleton D., Eisenberg S., Landzberg J., Mcgough M., Turk S., Schwartz M., Sundram P. S., Jain D., Zainea M., Bayron C., Karlsberg R., Dohad S., Lui H., Keen W., Westerhausen D., Khurana S., Agarwal H., Birchem J., Penny W., Chang M., Murphy S., Henry J., Schifferdecker B., Gilbert J. M., Chalavarya G., Eaton C., Schmedtje J. F., Christenson S., Dotani I., Denham D., Macdonell A., Gibson P., Rahman A., Al Joundi T., Assi N., Conrad G., Kotha P., Love M., Giesler G., Rubenstein H., Gamil D., Akright L., Krawczyk J., Cobler J., Wells T., Welker J., Foster R., Gilmore R., Anderson J., Jacoby D., Gardner G., Dandillaya R., Vora K., Kostis J., Hunter J., Laxson D., Ball E., Lopes R., Egydio F., Kawakami A., Oliveira J., Wozniak J., Matthews A., Ratky C., Valiris J., Berdan L., Hepditch A., Quintero K., Rorick T., Westbrook M., Pascual A., Rovito C., Bezault M., Drouet E., Simon T., Alsweiler C., Luyten A., Butters J., Griffith L., Shaw M., Grunberg L., Islam S., Bregeault M. -F., Bougon N., Faustino D., Fontecave S., Murphy J., Verrier M., Agnetti V., Andersen D., Badreddine E., Bekkouche M., Bouancheau C., Brigui I., Brocklehurst M., Cianciarulo J., Devaul D., Domokos S., Gache C., Gobillot C., Guillou S., Healy J., Heath M., Jaiwal G., Javierre C., Labeirie J., Monier M., Morales U., Mrabti A., Mthombeni B., Okan B., Smith L., Sheller J., Sopena S., Pellan V., Benbernou F., Bengrait N., Lamoureux M., Kralova K., Scemama M., Bejuit R., Coulange A., Berthou C., Repincay J., Lorenzato C., Etienne A., Gouet V., Normand M., Ourliac A., Rondel C., Adamo A., Beltran P., Barraud P., Dubois-Gache H., Halle B., Metwally L., Mourgues M., Sotty M., Vincendet M., Cotruta R., Chengyue Z., Fournie-Lloret D., Morrello C., Perthuis A., Picault P., Zobouyan I., Dempsey M. 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K., Bhansali P., Borse R., Rahul P., Das S., Kumar V., Abdullakutty J., Saathe S., Palimkar P., Sathe S., Atar S., Shechter M., Mosseri M., Arbel Y., Ehud C., Ofer H., Lotan C., Rosenschein U., Katz A., Henkin Y., Francis A., Klutstein M., Nikolsky E., Zukermann R., Turgeman Y., Halabi M., Marmor A., Kornowski R., Jonas M., Amir O., Hasin Y., Rozenman Y., Fuchs S., Zvi V., Hussein O., Gavish D., Vered Z., Caraco Y., Elias M., Tov N., Wolfovitz E., Lishner M., Elias N., Piovaccari G., De Pellegrin A., Garbelotto R., Guardigli G., Marco V., Licciardello G., Auguadro C., Scalise F., Cuccia C., Salvioni A., Musumeci G., Senni M., Calabro P., Novo S., Faggiano P., Metra M., De Cesare N. B., Berti S., Cavallini C., Puccioni E., Galvani M., Tespili M., Piatti P., Palvarini M., De Luca G., Violini R., De Leo A., Olivari Z., Perrone Filardi P., Ferratini M., Racca V., Dai K., Shimatani Y., Kamiya H., Ando K., Takeda Y., Morino Y., Hata Y., Kimura K., Kishi K., Michishita I., Uehara H., Higashikata T., Hirayama A., Hirooka K., Doi Y., Sakagami S., Taguchi S., Koike A., Fujinaga H., Koba S., Kozuma K., Kawasaki T., Ono Y., Shimizu M., Katsuda Y., Wada A., Shinke T., Ako J., Fujii K., Takahashi T., Sakamoto T., Nakao K., Furukawa Y., Sugino H., Tamura R., Mano T., Uematsu M., Utsu N., Ito K., Haraguchi T., Sato K., Ueda Y., Nishibe A., Fujimoto K., Masutani M., Yoon J. H., Kim H. -L., Park H. S., Chae I. -H., Kim M. H., Jeong M. H., Rha S., Kim C., Kim H. -S., Kim H. Y., Hong T., Tahk S. -J., Kim Y., Busmane A., Pontaga N., Strelnieks A., Mintale I., Sime I., Petrulioniene Z., Kavaliauskiene R., Jurgaitiene R., Sakalyte G., Slapikas R., Norkiene S., Misonis N., Kibarskis A., Kubilius R., Bojovski S., Lozance N., Kjovkaroski A., Doncovska S., Ong T. K., Kasim S., Maskon O., Kandasamy B., Liew H. B., Wan Mohamed W. M. I., Garcia Castillo A., Carrillo Calvillo J., Fajardo Campos P., Nunez Fragoso J. C., Bayram Llamas E. A., Alcocer Gamba M. A., Carranza Madrigal J., Gonzalez Salas L. G., Lopez Rosas E., Gonzalez Diaz B., Salcido Vazquez E., Nacoud Ackar A., Llamas Esperon G. A., Martinez Sanchez C. R., Guerrero De Leon M., Suarez Otero R., Fanghanel Salmon G., Perez Rios J. A., Garza Ruiz J. A., Breedveld R. W., Feenema-Aardema M., Borger-Van Der Burg A., Hoogslag P. A., Suryapranata H., Oomen A., Van Haelst P., Wiersma J. J., Basart D., Van Der Wal R. M., Zwart P., Monraats P., Van Kesteren H., Karalis I., Jukema J., Verdel G. J., Brueren B. R., Troquay R. P., Viergever E. P., Al-Windy N. Y., Bartels G. L., Cornel J. H., Hermans W. R., Herrman J. P., Bos R. J., Groutars R. G., Van Der Zwaan C. C., Kaplan R., Lionarons R., Ronner E., Groenemeijer B. E., Bronzwaer P. N., Liem A. A., Rensing B. J., Bokern M. J., Nijmeijer R., Hersbach F. M., Willems F. F., Gosselink A. T., Rasoul S., Elliott J., Wilkins G., Fisher R., Scott D., Hart H., Stewart R., Harding S., Ternouth I., Fisher N., Wilson S., Aitken D., Anscombe R., Davidson L., Tomala T., Nygard O., Sparby J. A., Andersen K., Gullestad L., Jortveit J., Munk P. S., Singsaas E. G., Hurtig U., Calderon Ticona J. R., Durand Velasquez J. R., Negron Miguel S. A., Sanabria Perez E. S., Carrion Chambilla J. M., Chavez Ayala C. A., Castillo Leon R. P., Vargas Gonzales R. J., Hernandez Zuniga J. D., Camacho Cosavalente L. A., Bravo Mannucci J. E., Heredia Landeo J., Llerena Navarro N. C., Roldan Concha Y. M., Rodriguez Chavez V. E., Anchante Hernandez H. A., Zea Nunez C. A., Mogrovejo Ramos W., Ferrolino A., Sy R. A. G., Tirador L., Sy R. G., Matiga G., Coching R. M., Bernan A., Rogelio G., Morales D. D., Tan E., Sulit D. J., Wlodarczak A., Jaworska K., Skonieczny G., Pawlowicz L., Wojewoda P., Busz-Papiez B., Bednarski J., Goch A., Staneta P., Dulak E., Saminski K., Krasowski W., Sudnik W., Zurakowski A., Skorski M., Miklaszewicz B., Kubica J., Andrzej Lipko J., Kostarska-Srokosz E., Piepiorka M., Drzewiecka A., Stasiewski A., Blicharski T., Bystryk L., Szpajer M., Korol M., Czerski T., Mirek-Bryniarska E., Gniot J., Lubinski A., Gorny J., Franek E., Raczak G., Szwed H., Monteiro P., Mesquita Bastos J., Pereira H. H., Martins D., Seixo F., Mendonca C., Botelho A., Caetano F., Minescu B., Istratoaie O., Tesloianu D. N., Cristian G., Dumitrescu S., Podoleanu C. G., Constantinescu M. C., Bengus C. M., Militaru C., Rosu D., Parepa I. R., Matei A. V., Alexandru T. M., Malis M., Coman I., Stanescu-Cioranu R., Dimulescu D., Shvarts Y., Orlikova O., Kobalava Z., Barbarash O. L., Markov V., Lyamina N., Gordienko A., Zrazhevsky K., Vishnevsky A. Y., Gurevich V., Stryuk R., Lomakin N. V., Bokarev I., Khlevchuk T., Shalaev S., Khaisheva L., Chizhov P., Viktorova I., Osokina N., Shchekotov V., Akatova E., Chumakova G., Libov I., Voevoda M. I., Tretyakova T. V., Baranov E., Shustov S., Yakushin S., Gordeev I., Khasanov N., Reshetko O., Sotnikova T., Molchanova O., Nikolaev K., Gapon L., Baranova E., Shogenov Z., Kosmachova E., Povzun A., Egorova L., Tyrenko V. V., Ivanov I. G., Ilya M., Kanorsky S., Simic D., Ivanovic N., Davidovic G., Tasic N., Asanin M. R., Stojic S., Apostolovic S. R., Ilic S., Putnikovic Tosic B., Stankovic A., Arandjelovic A., Radovanovic S., Todic B., Balinovac J., Dincic D. V., Seferovic P., Karadzic A., Dodic S., Dimkovic S., Jakimov T., Poh K. -K., Ong H. Y., Tang I-Shing J., Micko K., Nociar J., Pella D., Fulop P., Hranai M., Palka J., Mazur J., Majercak I., Dzupina A., Fazekas F., Gonsorcik J., Bugan V., Selecky J., Kamensky G., Strbova J., Smik R., Dukat A., Zuran I., Poklukar J., Cernic Suligoj N., Cevc M., Cyster H. P., Ranjith N., Corbett C., Bayat J., Makotoko E. M., du Toit Theron H., Kapp I. E., de V Basson M. M., Lottering H., Van Aswegen D., Van Zyl L. J., Sebastian P. J., Pillay T., Saaiman J. A., Commerford P. J., Cassimjee S., Riaz G., Ebrahim I. O., Sarvan M., Mynhardt J. H., Reuter H., Moodley R., Vida M., Cequier Fillat A. R., Bodi Peris V., Fuentes Jimenez F., Marin F., Cruz Fernandez J. M., Hidalgo Urbano R. J., Gil-Extremera B., Toledo P., Worner Diz F., Garcia-Dorado D., Iniguez A., Gonzalez-Juanatey J. R., Fernandez Portales J., Civeira Murillo F., Matas Pericas L., Zamorano J. L., De Mora Martin M., Bruguera Cortada J., Alonso Martin J. J., Serrano Antolin J. M., De Berrazueta Fernandez J. R., Vazquez de Prada J. A., Diaz Fernandez J. F., Garcia Lledo J. A., Cosin Sales J., Botas Rodriguez J., Gusi Tragant G., Benedicto A., Gonzalez-Juanatey C., Camprubi Potau M., Plaza Perez I., De La Tassa C. M., Loma-Osorio Rincon P., Balaguer Recena J., Escudier J. M., Payeras A. C., Alonso Orcajo N., Valdivielso P., Constantine G., Haniffa R., Tissera N., Amarasekera S., Ponnamperuma C., Fernando N., Fernando K., Jayawardena J., Wijeyasingam S., Ranasinghe G., Ekanayaka R., Mendis S., Senaratne V., Mayurathan G., Sirisena T., Rajapaksha A., Herath J. I., Amarasena N., Berglund S., Rasmanis G., Vedin O., Witt N., Mourtzinis G., Nicol P., Hansen O., Romeo S., Agergaard Jensen S., Torstensson I., Ahremark U., Sundelin T., Moccetti T., Muller C., Mach F., Binde R., Tsai W. -C., Ueng K. -C., Lai W. -T., Liu M. -E., Hwang J. -J., Yin W. -H., Hsieh I. -C., Hsieh M. -J., Lin W. H., Kuo J. -Y., Huang T. -Y., Fang C. -Y., Kaewsuwanna P., Soonfuang W., Jintapakorn W., Sukonthasarn A., Wongpraparut N., Sastravaha K., Sansanayudh N., Kehasukcharoen W., Piyayotai D., Chotnoparatpat P., Camsari A., Kultursay H., Mutlu B., Ersanli M., Demirtas M., Kirma C., Ural E., Koldas L., Karpenko O., Prokhorov A., Vakaluyk I., Myshanych H., Reshotko D., Batushkin V., Rudenko L., Kovalskyi I., Kushnir M., Tseluyko V., Mostovoy Y., Stanislavchuk M., Kyiak Y., Karpenko Y., Malynovsky Y., Klantsa A., Kutniy O., Amosova E., Tashchuk V., Leshchuk O., Rishko M., Kopytsya M., Yagensky A., Vatutin M., Bagriy A., Barna O. M., Ushakov O., Dzyak G., Goloborodko B., Rudenko A., Zheleznyy V., Trevelyan J., Zaman A., Lee K., Moriarty A., Aggarwal R. K., Clifford P., Wong Y. -K., Iqbal S. M., Subkovas E., Braganza D., Sarkar D., Storey R., Griffiths H., McClure S., Muthusamy R., Smith S., Kurian J., Levy T., Barr C., Kadr H., Gerber R., Simaitis A., Soran H., Mathur A., Brodison A., Ayaz M., Cheema M., Oliver R., Thackray S., Mudawi T., Rahman G., Sultan A., Sharman D., Sprigings D., Butler R., Wilkinson P., Lip G. Y., Halcox J., Gallagher S., Ossei-Gerning N., Vardi G., Baldari D., Brabham D., Treasure II C., Dahl C., Palmer B., Wiseman A., Puri S., Mohart A. E., Ince C., Flores E., Wright S., Cheng S. -C., Rosenberg M., Rogers W., Kosinski E., Forgosh L., Waltman J., Khan M., Shoukfeh M., Dagher G., Cambier P., Lieber I., Kumar P., East C., Krichmar P., Hasan M., White L., Knickelbine T., Haldis T., Gillespie E., Amidon T., Suh D., Arif I., Abdallah M., Akhter F., Carlson E., D'Urso M., El-Ahdab F., Nelson W., Moriarty K., Harris B., Cohen S., Carter L., Doty D., Sabatino K., Haddad T., Malik A., Rao S., Mulkay A., Jovin I., Klancke K., Malhotra V., Devarapalli S. K., Koren M., Chandna H., Dodds III G., Goraya T., Bengston J., Janik M., Moran J., Sumner A., Kobayashi J., Davis W., Yazdani S., Pasquini J., Thakkar M., Vedere A., Leimbach W., Rider J., Fenton S., Singh N., Shah A. V., Janosik D., Pepine C., Berman B., Gelormini J., Daniels C., Richard K., Keating F., Kondo N. I., Shetty S., Levite H., Waider W., Takata T., Abu-Fadel M., Shah V., Aggarwal R., Izzo M., Kumar A., Hattler B., Do R., Link C., Bortnick A., Kinzfogl III G., Ghitis A., Larry J., Teufel E., Kuhlman P., Mclaurin B., Zhang W., Thew S., Abbas J., White M., Islam O., Subherwal S., Ranadive N., Vakili B., Gring C., Henderson D., Schuchard T., Farhat N., Kline G., Mahal S., Whitaker J., Speirs S., Andersen R., Daboul N., Horwitz P., Zahr F., Ponce G., Jafar Z., Mcgarvey J., Panchal V., Voyce S., Blok T., Sheldon W., Azizad M. M., Schmalfuss C., Picone M., Pederson R., Herzog W., Friedman K., Lindsey J., Nowins R., Timothy E., Leonard P., Lepor N., El Shahawy M., Weintraub H., Irimpen A., Alonso A., May W., Christopher D., Galski T., Chu A., Mody F., Ramin E., Hodes Z., Rossi J., Rose G., Fairlamb J., Lambert C., Raisinghani A., Abbate A., Vetrovec G., King M., Carey C., Gerber J., Younis L., Park H. T., Vidovich M., Knutson T., Friedman D., Chaleff F., Loussararian A., Rozeman P., Kimmelstiel C., Kuvin J., Silver K., Foster M., Tonnessen G., Espinoza A., Amlani M., Wali A., Malozzi C., Jong G. T., Massey C., Wattanakit K., O'Donnell P. J., Singal D., Jaffrani N., Banuru S., Fisher D., Xenakis M., Perlmutter N., Bhagwat R., Strader J., Blonder R., Akyea-Djamson A., Labroo A., Marais H. J., Claxton E., Weiss R., Kathryn R., Berk M., Rossi P., Joshi P., Khera A., Khaira A. S., Kumkumian G., Lupovitch S., Purow J., Welka S., Hoffman D., Fischer S., Soroka E., Eagerton D., Pancholy S., Ray M., Erenrich N., Farrar M., Pollock S., French W. J., Diamantis S., Guy D., Gimple L., Neustel M., Schwartz S., Pereira E., Albert S., Spriggs D., Strain J., Mittal S., Vo A., Chane M., Hall J., Vijay N., Lotun K., Lester F. M., Nahhas A., Pope T., Nager P., Vohra R., Sharma M., Bashir R., Ahmed H., Berlowitz M., Fishberg R., Barrucco R., Yang E., Radin M., Sporn D., Stapleton D., Eisenberg S., Landzberg J., Mcgough M., Turk S., Schwartz M., Sundram P. S., Jain D., Zainea M., Bayron C., Karlsberg R., Dohad S., Lui H., Keen W., Westerhausen D., Khurana S., Agarwal H., Birchem J., Penny W., Chang M., Murphy S., Henry J., Schifferdecker B., Gilbert J. M., Chalavarya G., Eaton C., Schmedtje J. F., Christenson S., Dotani I., Denham D., Macdonell A., Gibson P., Rahman A., Al Joundi T., Assi N., Conrad G., Kotha P., Love M., Giesler G., Rubenstein H., Gamil D., Akright L., Krawczyk J., Cobler J., Wells T., Welker J., Foster R., Gilmore R., Anderson J., Jacoby D., Gardner G., Dandillaya R., Vora K., Kostis J., Hunter J., Laxson D., Ball E., Lopes R., Egydio F., Kawakami A., Oliveira J., Wozniak J., Matthews A., Ratky C., Valiris J., Berdan L., Hepditch A., Quintero K., Rorick T., Westbrook M., Pascual A., Rovito C., Bezault M., Drouet E., Simon T., Alsweiler C., Luyten A., Butters J., Griffith L., Shaw M., Grunberg L., Islam S., Bregeault M. -F., Bougon N., Faustino D., Fontecave S., Murphy J., Verrier M., Agnetti V., Andersen D., Badreddine E., Bekkouche M., Bouancheau C., Brigui I., Brocklehurst M., Cianciarulo J., Devaul D., Domokos S., Gache C., Gobillot C., Guillou S., Healy J., Heath M., Jaiwal G., Javierre C., Labeirie J., Monier M., Morales U., Mrabti A., Mthombeni B., Okan B., Smith L., Sheller J., Sopena S., Pellan V., Benbernou F., Bengrait N., Lamoureux M., Kralova K., Scemama M., Bejuit R., Coulange A., Berthou C., Repincay J., Lorenzato C., Etienne A., Gouet V., Normand M., Ourliac A., Rondel C., Adamo A., Beltran P., Barraud P., Dubois-Gache H., Halle B., Metwally L., Mourgues M., Sotty M., Vincendet M., Cotruta R., Chengyue Z., Fournie-Lloret D., Morrello C., Perthuis A., Picault P., Zobouyan I., Dempsey M. A., and McClanahan M. A.

Abstract

Background: After acute coronary syndrome, diabetes conveys an excess risk of ischaemic cardiovascular events. A reduction in mean LDL cholesterol to 1·4–1·8 mmol/L with ezetimibe or statins reduces cardiovascular events in patients with an acute coronary syndrome and diabetes. However, the efficacy and safety of further reduction in LDL cholesterol with an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) after acute coronary syndrome is unknown. We aimed to explore this issue in a prespecified analysis of the ODYSSEY OUTCOMES trial of the PCSK9 inhibitor alirocumab, assessing its effects on cardiovascular outcomes by baseline glycaemic status, while also assessing its effects on glycaemic measures including risk of new-onset diabetes. Methods: ODYSSEY OUTCOMES was a randomised, double-blind, placebo-controlled trial, done at 1315 sites in 57 countries, that compared alirocumab with placebo in patients who had been admitted to hospital with an acute coronary syndrome (myocardial infarction or unstable angina) 1–12 months before randomisation and who had raised concentrations of atherogenic lipoproteins despite use of high-intensity statins. Patients were randomly assigned (1:1) to receive alirocumab or placebo every 2 weeks; randomisation was stratified by country and was done centrally with an interactive voice-response or web-response system. Alirocumab was titrated to target LDL cholesterol concentrations of 0·65–1·30 mmol/L. In this prespecified analysis, we investigated the effect of alirocumab on cardiovascular events by glycaemic status at baseline (diabetes, prediabetes, or normoglycaemia)—defined on the basis of patient history, review of medical records, or baseline HbA1c or fasting serum glucose—and risk of new-onset diabetes among those without diabetes at baseline. The primary endpoint was a composite of death from coronary heart disease, non-fatal myocardial infarction, fatal or non-fatal ischaemic stroke, or unstable angina requiring

Published
2019

19. Reconstructing lower Bajocian carbon cycle perturbations using phosphorus content, carbon isotopes and sediments accumulation rates

Author

Suchéras-Marx, Baptiste, Suan, Guillaume, Giraud, Fabienne, Mattioli, Emanuela, Khozyem, Hassan, Mazur, Jean-Charles, Mazur, J. C., Fantasias, Alicia, Adatte, Thierry, Centre européen de recherche et d'enseignement des géosciences de l'environnement (CEREGE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de Géologie de Lyon - Terre, Planètes, Environnement (LGL-TPE), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut national des sciences de l'Univers (INSU - CNRS)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences de la Terre (ISTerre), Institut national des sciences de l'Univers (INSU - CNRS)-Institut de recherche pour le développement [IRD] : UR219-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Gustave Eiffel-Université Grenoble Alpes (UGA), Université de Lausanne = University of Lausanne (UNIL), Aarhus University [Aarhus], and Suchéras-Marx, Baptiste

Subjects
[SDU.STU.ST]Sciences of the Universe [physics]/Earth Sciences/Stratigraphy, [SDU.STU.ST] Sciences of the Universe [physics]/Earth Sciences/Stratigraphy, [SDU.STU.PG] Sciences of the Universe [physics]/Earth Sciences/Paleontology, [SDU.STU.PG]Sciences of the Universe [physics]/Earth Sciences/Paleontology
Abstract

International audience; The lower Bajocian (Middle Jurassic) deposits record two successive carbon isotopes excursions (CIE) with a negative ~0.5‰ CIE near the Aalenian-Bajocian boundary followed by a more protracted positive ~1.5‰ CIE ending at the base of upper Bajocian deposits. Both events are observed in both northern and southern Tethys and have been attributed to a global carbon cycle perturbation. In order to constrain the possible cause of the lower Bajocian CIEs, we present new geochemical and sedimentological data from Chaudon-Norante (France) and Murtinheira (Portugal) sections. We have measured δ13Corg values and phosphorus content and calculated CaCO3, siliciclastics, organic matter and phosphorus accumulation rates using published astronomical age models. In the sections studied, there is no carbonate crisis as opposed to south Tethyan localities, pointing to a strong geographical control of calcium carbonate accumulation in the western Tethys during the Bajocian. Both sites record an increase in siliciclastics and phosphorus AR but relatively constant organic matter AR. The δ13Cbulk carbonate vs δ13Corg stratigraphic variations suggest that both negative and positive CIEs were likely caused by an increase in phosphorus and weathered carbon riverine input. Together, our new results suggest that this event was triggered by an increase in productivity and organic carbon burial. However, there are no recurrent black shales nor organic-rich deposits identified for this time interval in western Tethys. In summary, the lower Bajocian carbon cycle perturbation bears many similarities with the Valanginian event and direct comparison between both events may help to refine current hypotheses about the causes of Mesozoic positive CIEs.

Published
2020

20. Revising the self-report Strengths and Difficulties Questionnaire for Cross-Country Comparisons of Adolescent Mental Health Problems: The SDQ-R

Author

Duinhof, E.L., Lek, K.M., de Looze, M.E., Cosma, A.P., Mazur, J., Gobina, I., Wustner, A., Vollebergh, W.A.M., Stevens, G.W.J.M., Duinhof, E.L., Lek, K.M., de Looze, M.E., Cosma, A.P., Mazur, J., Gobina, I., Wustner, A., Vollebergh, W.A.M., and Stevens, G.W.J.M.

Abstract

Aims The Strengths and Difficulties Questionnaire (SDQ) has been used in many epidemiological studies to assess adolescent mental health problems, but cross-country comparisons of the self-report SDQ are scarce and so far failed to find a good-fitting, common, invariant measurement model across countries. The present study aims to evaluate and establish a version of the self-report SDQ that allows for a valid cross-country comparison of adolescent self-reported mental health problems. Methods Using the Health Behaviour in School-aged Children study, the measurement model and measurement invariance of the 20 items of the self-report SDQ measuring adolescent mental health problems were evaluated. Nationally representative samples of 11-, 13- and 15-year old adolescents (n = 33 233) from seven countries of different regions in Europe (Bulgaria, Germany, Greece, the Netherlands, Poland, Romania, Slovenia) were used. Results In order to establish a good-fitting and common measurement model, the five reverse worded items of the self-report SDQ had to be removed. Using this revised version of the self-report SDQ, the SDQ-R, partial measurement invariance was established, indicating that latent factor means assessing conduct problems, emotional symptoms, peer relationships problems and hyperactivity-inattention problems could be validly compared across the countries in this study. Results showed that adolescents in Greece scored relatively low on almost all problem subscales, whereas adolescents in Poland scored relatively high on almost all problem subscales. Adolescents in the Netherlands reported the most divergent profile of mental health problems with the lowest levels of conduct problems, low levels of emotional symptoms and peer relationship problems, but the highest levels of hyperactivity-inattention problems. Conclusions With six factor loadings being non-invariant, partial measurement invariance was established, indicati

Published
2020

21. Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error

Author

Fan, Q., Pozarickij, A., Tan, N.Y.Q., Guo, X., Verhoeven, V.J.M., Vitart, V., Guggenheim, J.A., Miyake, M., Tideman, J.W.L., Khawaja, A.P., Zhang, L., MacGregor, S., Hohn, R., Chen, P., Biino, G., Wedenoja, J., Saffari, S.E., Tedja, M.S., Xie, J, Lanca, C., Wang, Y.X., Sahebjada, S., Mazur, J., Mirshahi, A., Martin, N.G., Yazar, S., Pennell, C.E., Yap, M., Haarman, A.E.G., Enthoven, C.A., Polling, J., Hewitt, A.W., Jaddoe, V.W.V., Duijn, C.M. van, Hayward, C., Polasek, O., Tai, E.S., Yoshikatsu, H., Hysi, P.G., Young, T.L., Tsujikawa, A., Wang, J.J., Mitchell, P., Pfeiffer, N., Parssinen, O., Foster, P.J., Fossarello, M., Yip, S.P., Williams, C., Hammond, C.J., Jonas, J.B., He, M., Mackey, D.A., Wong, T.Y., Klaver, C.C.W., Saw, S.M., Baird, P.N., Cheng, C.Y., Fan, Q., Pozarickij, A., Tan, N.Y.Q., Guo, X., Verhoeven, V.J.M., Vitart, V., Guggenheim, J.A., Miyake, M., Tideman, J.W.L., Khawaja, A.P., Zhang, L., MacGregor, S., Hohn, R., Chen, P., Biino, G., Wedenoja, J., Saffari, S.E., Tedja, M.S., Xie, J, Lanca, C., Wang, Y.X., Sahebjada, S., Mazur, J., Mirshahi, A., Martin, N.G., Yazar, S., Pennell, C.E., Yap, M., Haarman, A.E.G., Enthoven, C.A., Polling, J., Hewitt, A.W., Jaddoe, V.W.V., Duijn, C.M. van, Hayward, C., Polasek, O., Tai, E.S., Yoshikatsu, H., Hysi, P.G., Young, T.L., Tsujikawa, A., Wang, J.J., Mitchell, P., Pfeiffer, N., Parssinen, O., Foster, P.J., Fossarello, M., Yip, S.P., Williams, C., Hammond, C.J., Jonas, J.B., He, M., Mackey, D.A., Wong, T.Y., Klaver, C.C.W., Saw, S.M., Baird, P.N., and Cheng, C.Y.

Abstract

Contains fulltext : 218869.pdf (publisher's version ) (Open Access), Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.

Published
2020

22. Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error

Author

Fan, Q. (Qiao), Pozarickij, A. (Alfred), Tan, N.Y.Q. (Nicholas Y. Q.), Guo, X. (Xiaobo), Verhoeven, V.J.M. (Virginie), Vitart, V. (Veronique), Guggenheim, J. (Jean), Miyake, M. (Masahiro), Tideman, J.W.L. (Willem), Khawaja, A.P. (Anthony), Zhang, L. (Liang), MacGregor, S. (Stuart), Höhn, R. (René), Chen, P. (Peng), Biino, G. (Ginevra), Wedenoja, J. (Juho), Saffari, S.E. (Seyed Ehsan), Tedja, M. (Milly), Xie, J. (Jing), Lanca, C. (Carla), Wang, Y.X. (Ya Xing), Sahebjada, S. (Srujana), Mazur, J. (Johanna), Mirshahi, A. (Alireza), Martin, N.G. (Nicholas), Yazar, S. (Seyhan), Pennell, C.E. (Craig), Yap, M.K.H. (Maurice K. H.), Haarman, A.E.G. (Annechien E. G.), Enthoven, C.A. (Clair A.), Polling, J.R. (Jan Roelof), Bailey-Wilson, J.E. (Joan E.), Veluchamy, A.B. (Amutha Barathi), Burdon, K.P. (Kathryn P.), Campbell, H. (Harry), Chen, L.J. (Li Jia), Chew, E.Y. (Emily Y.), Craig, J.E. (Jamie), Cumberland, P.M. (Phillippa M.), DeAngelis, M.M. (Margaret), Delcourt, C. (Cécile), Ding, X. (Xiaohu), Evans, D.M. (David M.), Gharahkhani, P. (Puya), Iglesias, A.I. (Adriana I.), Haller, T. (Toomas), Han, X. (Xikun), Hoang, Q. (Quan), Igo Jr., R.P. (Robert), Iyengar, S.K. (Sudha), Kähönen, M. (Mika), Kaprio, J. (Jaakko), Klein, B.E. (Barbara E.), Klein, R. (Ronald), Lass Jr., J.H. (Jonathan), Lee, K. (Kris), Lehtimäki, T. (Terho), Lewis, D.D. (Deyana D.), Li, Q. (Qing), Li, S.-M. (Shi-Ming), Lyytikäinen, L.-P. (Leo-Pekka), Meguro, A. (Akira), Metspalu, A. (Andres), Middlebrooks, C.D. (Candace D.), Mizuki, N. (Nobuhisa), Musolf, A.M. (Anthony M.), Nickels, S. (Stefan), Oexle, K. (Konrad), Pang, C.P. (Chi Pui), Paterson, A.D. (Andrew), Rahi, J.S. (Jugnoo S.), Raitakari, O. (Olli), Rudan, I. (Igor), Stambolian, D.E. (Dwight), Simpson, C.L. (Claire), Wang, N. (Ningli), Bin Wei, W. (Wen), Williams, K.M. (Katie M.), Wilson, J.F. (James), Wojciechowski, R. (Robert), Yamashiro, K. (Kenji), Yam, J.C.S. (Jason C. S.), Zhou, X. (Xiangtian), Aslam, T. (Tariq), Barman, S.A. (Sarah A.), Barrett, J.H. (Jenny H.), Bishop, P.N. (Paul), Blows, P. (Peter), Bunce, C. (Catey), Carare, R.O. (Roxana O.), Chakravarthy, U. (Usha), Chan, M. (Michelle), Chua, S.Y.L. (Sharon Y. L.), Crabb, D.P. (David), Cumberland, P.M. (Philippa M.), Day, A. (Alexander), Desai, P. (Parul), Dhillon, B. (Bal), Dick, A.D. (Andrew D.), Egan, C. (Cathy), Ennis, S. (Sarah), Fruttiger, M. (Marcus), Gallacher, J. (John), Garway-Heath, D.F. (David F.), Gibson, J. (Jane), Gore, D. (Dan), Hardcastle, A. (Alison), Harding, S.P. (Simon), Hogg, R. (Ruth), Keane, P.A. (Pearse A.), Khaw, S.P.T. (Sir Peng T.), Lascaratos, G. (Gerassimos), Lotery, A.J. (Andrew), Macgillivray, T. (Tom), Mackie, S. (Sarah), Martin, K. (Keith), McGaughey, M. (Michelle), McGuinness, B. (Bernadette), McKay, G.J. (Gareth), McKibbin, M. (Martin), Mitry, D. (Danny), Moore, T. (Tony), Morgan, J.E. (James E.), Muthy, Z.A. (Zaynah A.), O’Sullivan, E. (Eoin), Owen, C.G. (Chris G.), Patel, P. (Praveen), Paterson, E. (Euan), Peto, T. (Tünde), Petzold, A. (Axel), Rudnikca, A.R. (Alicja R.), Self, J. (Jay), Sivaprasad, S., Steel, D. (David), Stratton, I. (Irene), Strouthidis, N. (Nicholas), Sudlow, C. (Cathie), Thomas, D. (Dhanes), Trucco, E. (Emanuele), Tufail, A. (Adnan), Vernon, S.A. (Stephen A.), Viswanathan, A.C. (Ananth C.), Williams, K. (Katie), Woodside, J.V. (J.), Yates, M.M. (Max M.), Yip, J. (Jennifer), Zheng, Y. (Yalin), Hewit, A.W. (Alex), Jaddoe, V.W.V. (Vincent), Duijn, C.M. (Cornelia) van, Hayward, C. (Caroline), Polasek, O. (Ozren), Tai, E.S. (Shyong), Yoshikatsu, H. (Hosoda), Hysi, P.G. (Pirro G.), Young, T.L. (Terri L.), Tsujikawa, A. (Akitaka), Wang, J.J. (Jie Jing), Mitchell, P. (Paul), Pfeiffer, A.F.H. (Andreas), Pärssinen, O. (Olavi), Foster, P.J. (Paul), Fossarello, M. (Maurizio), Yip, S.P. (Shea Ping), Williams, C. (Cathy), Hammond, C.J. (Christopher), Jonas, J.B., He, M. (Mingguang), Mackey, D.A. (David), Wong, T.-Y. (Tien-Yin), Klaver, C.C.W. (Caroline), Saw, S-M. (Seang-Mei), Baird, P.N. (Paul), Cheng, C.-Y. (Ching-Yu), Fan, Q. (Qiao), Pozarickij, A. (Alfred), Tan, N.Y.Q. (Nicholas Y. Q.), Guo, X. (Xiaobo), Verhoeven, V.J.M. (Virginie), Vitart, V. (Veronique), Guggenheim, J. (Jean), Miyake, M. (Masahiro), Tideman, J.W.L. (Willem), Khawaja, A.P. (Anthony), Zhang, L. (Liang), MacGregor, S. (Stuart), Höhn, R. (René), Chen, P. (Peng), Biino, G. (Ginevra), Wedenoja, J. (Juho), Saffari, S.E. (Seyed Ehsan), Tedja, M. (Milly), Xie, J. (Jing), Lanca, C. (Carla), Wang, Y.X. (Ya Xing), Sahebjada, S. (Srujana), Mazur, J. (Johanna), Mirshahi, A. (Alireza), Martin, N.G. (Nicholas), Yazar, S. (Seyhan), Pennell, C.E. (Craig), Yap, M.K.H. (Maurice K. H.), Haarman, A.E.G. (Annechien E. G.), Enthoven, C.A. (Clair A.), Polling, J.R. (Jan Roelof), Bailey-Wilson, J.E. (Joan E.), Veluchamy, A.B. (Amutha Barathi), Burdon, K.P. (Kathryn P.), Campbell, H. (Harry), Chen, L.J. (Li Jia), Chew, E.Y. (Emily Y.), Craig, J.E. (Jamie), Cumberland, P.M. (Phillippa M.), DeAngelis, M.M. (Margaret), Delcourt, C. (Cécile), Ding, X. (Xiaohu), Evans, D.M. (David M.), Gharahkhani, P. (Puya), Iglesias, A.I. (Adriana I.), Haller, T. (Toomas), Han, X. (Xikun), Hoang, Q. (Quan), Igo Jr., R.P. (Robert), Iyengar, S.K. (Sudha), Kähönen, M. (Mika), Kaprio, J. (Jaakko), Klein, B.E. (Barbara E.), Klein, R. (Ronald), Lass Jr., J.H. (Jonathan), Lee, K. (Kris), Lehtimäki, T. (Terho), Lewis, D.D. (Deyana D.), Li, Q. (Qing), Li, S.-M. (Shi-Ming), Lyytikäinen, L.-P. (Leo-Pekka), Meguro, A. (Akira), Metspalu, A. (Andres), Middlebrooks, C.D. (Candace D.), Mizuki, N. (Nobuhisa), Musolf, A.M. (Anthony M.), Nickels, S. (Stefan), Oexle, K. (Konrad), Pang, C.P. (Chi Pui), Paterson, A.D. (Andrew), Rahi, J.S. (Jugnoo S.), Raitakari, O. (Olli), Rudan, I. (Igor), Stambolian, D.E. (Dwight), Simpson, C.L. (Claire), Wang, N. (Ningli), Bin Wei, W. (Wen), Williams, K.M. (Katie M.), Wilson, J.F. (James), Wojciechowski, R. (Robert), Yamashiro, K. (Kenji), Yam, J.C.S. (Jason C. S.), Zhou, X. (Xiangtian), Aslam, T. (Tariq), Barman, S.A. (Sarah A.), Barrett, J.H. (Jenny H.), Bishop, P.N. (Paul), Blows, P. (Peter), Bunce, C. (Catey), Carare, R.O. (Roxana O.), Chakravarthy, U. (Usha), Chan, M. (Michelle), Chua, S.Y.L. (Sharon Y. L.), Crabb, D.P. (David), Cumberland, P.M. (Philippa M.), Day, A. (Alexander), Desai, P. (Parul), Dhillon, B. (Bal), Dick, A.D. (Andrew D.), Egan, C. (Cathy), Ennis, S. (Sarah), Fruttiger, M. (Marcus), Gallacher, J. (John), Garway-Heath, D.F. (David F.), Gibson, J. (Jane), Gore, D. (Dan), Hardcastle, A. (Alison), Harding, S.P. (Simon), Hogg, R. (Ruth), Keane, P.A. (Pearse A.), Khaw, S.P.T. (Sir Peng T.), Lascaratos, G. (Gerassimos), Lotery, A.J. (Andrew), Macgillivray, T. (Tom), Mackie, S. (Sarah), Martin, K. (Keith), McGaughey, M. (Michelle), McGuinness, B. (Bernadette), McKay, G.J. (Gareth), McKibbin, M. (Martin), Mitry, D. (Danny), Moore, T. (Tony), Morgan, J.E. (James E.), Muthy, Z.A. (Zaynah A.), O’Sullivan, E. (Eoin), Owen, C.G. (Chris G.), Patel, P. (Praveen), Paterson, E. (Euan), Peto, T. (Tünde), Petzold, A. (Axel), Rudnikca, A.R. (Alicja R.), Self, J. (Jay), Sivaprasad, S., Steel, D. (David), Stratton, I. (Irene), Strouthidis, N. (Nicholas), Sudlow, C. (Cathie), Thomas, D. (Dhanes), Trucco, E. (Emanuele), Tufail, A. (Adnan), Vernon, S.A. (Stephen A.), Viswanathan, A.C. (Ananth C.), Williams, K. (Katie), Woodside, J.V. (J.), Yates, M.M. (Max M.), Yip, J. (Jennifer), Zheng, Y. (Yalin), Hewit, A.W. (Alex), Jaddoe, V.W.V. (Vincent), Duijn, C.M. (Cornelia) van, Hayward, C. (Caroline), Polasek, O. (Ozren), Tai, E.S. (Shyong), Yoshikatsu, H. (Hosoda), Hysi, P.G. (Pirro G.), Young, T.L. (Terri L.), Tsujikawa, A. (Akitaka), Wang, J.J. (Jie Jing), Mitchell, P. (Paul), Pfeiffer, A.F.H. (Andreas), Pärssinen, O. (Olavi), Foster, P.J. (Paul), Fossarello, M. (Maurizio), Yip, S.P. (Shea Ping), Williams, C. (Cathy), Hammond, C.J. (Christopher), Jonas, J.B., He, M. (Mingguang), Mackey, D.A. (David), Wong, T.-Y. (Tien-Yin), Klaver, C.C.W. (Caroline), Saw, S-M. (Seang-Mei), Baird, P.N. (Paul), and Cheng, C.-Y. (Ching-Yu)

Abstract

Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.

Published
2020
Full Text
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23. Revising the self-report Strengths and Difficulties Questionnaire for Cross-Country Comparisons of Adolescent Mental Health Problems: The SDQ-R

Author

Leerstoel Finkenauer, Leerstoel Schoot, Leerstoel Vollebergh, Youth in Changing Cultural Contexts, Duinhof, E.L., Lek, K.M., de Looze, M.E., Cosma, A.P., Mazur, J., Gobina, I., Wustner, A., Vollebergh, W.A.M., Stevens, G.W.J.M., Leerstoel Finkenauer, Leerstoel Schoot, Leerstoel Vollebergh, Youth in Changing Cultural Contexts, Duinhof, E.L., Lek, K.M., de Looze, M.E., Cosma, A.P., Mazur, J., Gobina, I., Wustner, A., Vollebergh, W.A.M., and Stevens, G.W.J.M.

Published
2020

24. Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error

Author

Fan, Q, Pozarickij, A, Tan, NYQ, Guo, X, Verhoeven, VJM, Vitart, V, Guggenheim, JA, Miyake, M, Tideman, JWL, Khawaja, AP, Zhang, L, MacGregor, S, Hoehn, R, Chen, P, Biino, G, Wedenoja, J, Saffari, SE, Tedja, MS, Xie, J, Lanca, C, Wang, YX, Sahebjada, S, Mazur, J, Mirshahi, A, Martin, NG, Yazar, S, Pennell, CE, Yap, M, Haarman, AEG, Enthoven, CA, Polling, J, Hewitt, AW, Jaddoe, VWV, van Duijn, CM, Hayward, C, Polasek, O, Tai, E-S, Yoshikatsu, H, Hysi, PG, Young, TL, Tsujikawa, A, Wang, JJ, Mitchell, P, Pfeiffer, N, Parssinen, O, Foster, PJ, Fossarello, M, Yip, SP, Williams, C, Hammond, CJ, Jonas, JB, He, M, Mackey, DA, Wong, T-Y, Klaver, CCW, Saw, S-M, Baird, PN, Cheng, C-Y, Fan, Q, Pozarickij, A, Tan, NYQ, Guo, X, Verhoeven, VJM, Vitart, V, Guggenheim, JA, Miyake, M, Tideman, JWL, Khawaja, AP, Zhang, L, MacGregor, S, Hoehn, R, Chen, P, Biino, G, Wedenoja, J, Saffari, SE, Tedja, MS, Xie, J, Lanca, C, Wang, YX, Sahebjada, S, Mazur, J, Mirshahi, A, Martin, NG, Yazar, S, Pennell, CE, Yap, M, Haarman, AEG, Enthoven, CA, Polling, J, Hewitt, AW, Jaddoe, VWV, van Duijn, CM, Hayward, C, Polasek, O, Tai, E-S, Yoshikatsu, H, Hysi, PG, Young, TL, Tsujikawa, A, Wang, JJ, Mitchell, P, Pfeiffer, N, Parssinen, O, Foster, PJ, Fossarello, M, Yip, SP, Williams, C, Hammond, CJ, Jonas, JB, He, M, Mackey, DA, Wong, T-Y, Klaver, CCW, Saw, S-M, Baird, PN, and Cheng, C-Y

Abstract

Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.

Published
2020

25. AN INTERNATIONAL COOPERATION BY USING AN ALL-ENCOMPASSING PASSIVE RADON MONITOR

Author

Tommasino, L., Chen, J., Falcolmer, R., DeFelice, F., Cardellini, F., Trevisi, R., Leonardi, F., Magnoni, M., Chiaberto, E., Agnesod, G., Faure, Ragani M., Espinosa, G., Golzarri, J., Kozak, K., and Mazur, J.

Abstract

The recently developed radon film-badge makes it possible to measure radon indoors, in soil, in water and/or in aqueous media (e.g. mud). As a result of its wide response linearity, this monitor has been successfully used to measure radon in-water with concentrations from 10 to ~10 000 Bq/L. By exploiting the unique characteristics of this badge, a mini-survey has been carried out by Health Canada in which radon in water was measured from 12 private wells, as well as in tap water originating from the Ottawa River. Due to the widespread interest of different laboratories in using these passive monitors, laboratories were provided with plastic films to construct their own badges by using in-house CR-39 detectors. Monitors were then irradiated by a known radon concentration at the National Institute of Radiation Metrology (ENEA)’s radon chamber and sent back to each laboratory for processing and counting. Even though these laboratories have been using different etching- and counting-procedures, the film-badge responses varied only within ~12%.

Published
2018

28. Revising the self-report strengths and difficulties questionnaire for cross-country comparisons of adolescent mental health problems: the SDQ-R

Author

Duinhof, E.L., Lek, K.M., de Looze, M.E., Cosma, A.P., Mazur, J., Gobina, I., Wustner, A., Vollebergh, W.A.M., Stevens, G.W.J.M., Leerstoel Finkenauer, Leerstoel Schoot, Leerstoel Vollebergh, and Youth in Changing Cultural Contexts

Subjects
Conduct Disorder, Cross-Cultural Comparison, Male, medicine.medical_specialty, Adolescent, Epidemiology, Emotions, Slovenia, Adolescents, Peer Group, minority issues and cross cultural psychiatry, 03 medical and health sciences, 0302 clinical medicine, Germany, Surveys and Questionnaires, Comparative research, medicine, Humans, Interpersonal Relations, 0501 psychology and cognitive sciences, Measurement invariance, 030212 general & internal medicine, Bulgaria, Child, Netherlands, Cross country, Greece, Romania, Mental Disorders, Self, 05 social sciences, Public Health, Environmental and Occupational Health, Reproducibility of Results, Original Articles, Strengths and Difficulties Questionnaire, Mental health, Test (assessment), Psychiatry and Mental health, Attention Deficit Disorder with Hyperactivity, validation study, Female, Poland, Self Report, Psychology, mental health, 050104 developmental & child psychology, Clinical psychology
Abstract

Aims The Strengths and Difficulties Questionnaire (SDQ) has been used in many epidemiological studies to assess adolescent mental health problems, but cross-country comparisons of the self-report SDQ are scarce and so far failed to find a good-fitting, common, invariant measurement model across countries. The present study aims to evaluate and establish a version of the self-report SDQ that allows for a valid cross-country comparison of adolescent self-reported mental health problems. Methods Using the Health Behaviour in School-aged Children study, the measurement model and measurement invariance of the 20 items of the self-report SDQ measuring adolescent mental health problems were evaluated. Nationally representative samples of 11-, 13- and 15-year old adolescents (n = 33 233) from seven countries of different regions in Europe (Bulgaria, Germany, Greece, the Netherlands, Poland, Romania, Slovenia) were used. Results In order to establish a good-fitting and common measurement model, the five reverse worded items of the self-report SDQ had to be removed. Using this revised version of the self-report SDQ, the SDQ-R, partial measurement invariance was established, indicating that latent factor means assessing conduct problems, emotional symptoms, peer relationships problems and hyperactivity-inattention problems could be validly compared across the countries in this study. Results showed that adolescents in Greece scored relatively low on almost all problem subscales, whereas adolescents in Poland scored relatively high on almost all problem subscales. Adolescents in the Netherlands reported the most divergent profile of mental health problems with the lowest levels of conduct problems, low levels of emotional symptoms and peer relationship problems, but the highest levels of hyperactivity-inattention problems. Conclusions With six factor loadings being non-invariant, partial measurement invariance was established, indicating that the 15-item SDQ-R could be used in our cross-country comparison of adolescent mental health problems. To move the field of internationally comparative research on adolescent mental health forward, studies should test the applicability of the SDQ-R in other countries in- and outside Europe, continue to develop the SDQ-R as a cross-country invariant measure of adolescent mental health, and examine explanations for the found country differences in adolescent mental health problems.

Published
2019

29. Effects of Alirocumab on Cardiovascular Events After Coronary Bypass Surgery

Author

Szarek, M, Bhatt, DL, Bittner, VA, Diaz, R, Edelberg, JM, Hanotin, C, Harrington, RA, Jukema, JW, Letierce, A, Moryusef, A, Pordy, R, Lopez, GAR, Roe, MT, White, HD, Zeiher, AM, Steg, PG, Schwartz, GG, Aylward, PE, Drexel, H, Sinnaeve, P, Dilic, M, Goodman, SG, Prieto, JC, Yong, H, Lopez-Jaramillo, P, Pecin, I, Reiner, Z, Ostadal, P, Poulsen, SH, Viigimaa, M, Nieminen, MS, Danchin, N, Chumburidze, V, Tse, HF, Xavier, D, Zahger, D, Valgimigli, M, Kimura, T, Kim, HS, Kim, SH, Erglis, A, Laucevicius, A, Kedev, S, Yusoff, K, Alings, M, Halvorsen, S, Flores, RMC, Sy, RG, Budaj, A, Morais, J, Dorobantu, M, Karpov, Y, Ristic, AD, Chua, T, Murin, J, Fras, Z, Tunon, J, de Silva, HA, Muller, C, Ray, KK, Vogel, R, Chaitman, B, Kelsey, SF, Olsson, AG, Rouleau, JL, Simoons, ML, Alexander, K, Meloni, C, Rosenson, R, Sijbrands, EJG, Alexander, JH, Armaganijan, L, Bagai, A, Bahit, MC, Brennan, JM, Clifton, S, DeVore, AD, Deloatch, S, Dickey, S, Dombrowski, K, Ducrocq, G, Eapen, Z, Endsley, P, Eppinger, A, Hess, CN, Hlatky, MA, Jordan, JD, Knowles, JW, Kolls, BJ, Kong, DF, Leonardi, S, Lillis, L, Maron, DJ, Marcus, J, Mathews, R, Mehta, RH, Mentz, RJ, Moreira, HG, Patel, CB, Pereira, SB, Perkins, L, Povsic, TJ, Puymirat, E, Jones, WS, Shah, BR, Sherwood, MW, Stringfellow, K, Sujjavanich, D, Toma, M, Trotter, C, van Diepen, SFP, Wilson, MD, Yan, ATK, Schiavi, LB, Garrido, M, Alvarisqueta, AF, Sassone, SA, Bordonava, AP, De Lima, AEA, Schmidberg, JM, Duronto, EA, Caruso, OC, Novaretto, LP, Hominal, MA, Montana, OR, Caccavo, A, Vilamajo, OAG, Lorenzatti, AJ, Cartasegna, LR, Paterlini, GA, Mackinnon, IJ, Caime, GD, Amuchastegui, M, Codutti, OR, Jure, HO, Bono, JOE, Hrabar, AD, Vallejos, JA, Rodolfo, AAG, Novoa, F, Patocchi, CA, Zaidman, CJ, Giuliano, ME, Dran, RD, Vico, ML, Carnero, GS, Guzman, PN, Allende, JCM, Brasca, DFG, Labarta, MHB, Nani, S, Blumberg, EDS, Colombo, HR, Liberman, A, Luciardi, HL, Waisman, GD, Berli, MA, Duran, ROG, Cestari, HG, Luquez, HA, Giordano, JA, Saavedra, SS, Waites, JH, Collins, N, Soward, A, Hii, CLS, Shaw, J, Arstall, MA, Horowitz, J, Rogers, JF, Colquhoun, D, Flores, REO, Roberts-Thomson, P, Raffel, O, Lehman, SJ, Coverdale, SGM, Garrahy, PJ, Starmer, G, Sader, M, Carroll, PA, Zweiker, R, Hoppe, U, Huber, K, Berger, R, Weidinger, F, Faes, D, Hermans, K, Pirenne, B, Leone, A, Hoffer, E, Vrolix, MCM, De Wolf, L, Wollaert, B, Castadot, M, Dujardin, K, Beauloye, C, Vervoort, G, Striekwold, H, Convens, C, Roosen, J, Barbato, E, Claeys, M, Cools, F, Terzic, I, Barakovic, F, Midzic, Z, Pojskic, B, Fazlibegovic, E, Durak-Nalbantic, A, Vulic, D, Muslibegovic, A, Reis, G, Sousa, L, Nicolau, JC, Giorgeto, FE, Silva, RP, Maia, LN, Rech, R, Rossi, PRF, Cerqueira, MJAG, Duda, N, Kalil, R, Kormann, A, Abrantes, JAM, Pimentel, P, Soggia, AP, de Santos, MON, Neuenschwander, F, Bodanese, LC, Michalaros, YL, Eliaschewitz, FG, Vidotti, MH, Leaes, PE, Botelho, RV, Kaiser, S, Manenti, ERFF, Precoma, DB, Jorge, JCM, Silva, PGMD, Silveira, JA, 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Fishberg, R, Barrucco, R, Yang, E, Radin, M, Sporn, D, Eisenberg, S, Landzberg, J, Mcgough, M, Turk, S, Schwartz, M, Sundram, PS, Jain, D, Zainea, M, Bayron, C, Karlsberg, R, Lui, H, Keen, W, Westerhausen, D, Khurana, S, Agarwal, H, Birchem, J, Penny, W, Chang, M, Gilbert, JM, Chalavarya, G, Eaton, C, Schmedtje, JF, Christenson, S, Denham, D, Macdonell, A, Gibson, P, Rahman, A, Al Joundi, T, Conrad, G, Kotha, P, Love, M, Giesler, G, Rubenstein, H, Akright, L, Schifferdecker, B, Krawczyk, J, Wells, T, Welker, J, Foster, R, Gilmore, R, Anderson, J, Jacoby, D, Gardner, G, Dandillaya, R, Vora, K, Kostis, J, Hunter, J, Laxson, D, Ball, E, İÜC, and Ege Üniversitesi

Subjects
Male, medicine.medical_specialty, Acute coronary syndrome, alirocumab, 030204 cardiovascular system & hematology, Antibodies, Monoclonal, Humanized, lipids, PCSK9, 03 medical and health sciences, 0302 clinical medicine, Postoperative Complications, Double-Blind Method, coronary artery bypass graft, Internal medicine, medicine, Humans, Cardiac and Cardiovascular Systems, 030212 general & internal medicine, Myocardial infarction, cardiovascular diseases, Acute Coronary Syndrome, Coronary Artery Bypass, Alirocumab, Aged, Kardiologi, business.industry, Unstable angina, Hazard ratio, cholesterol, Middle Aged, medicine.disease, surgical procedures, operative, Bypass surgery, Cardiovascular Diseases, Cardiology, Drug Therapy, Combination, Female, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine, business, Mace
Abstract

Sherwood, Matthew/0000-0002-4305-5883; Taskinen, Marja-Riitta/0000-0002-6229-3588; Leonardi, Sergio/0000-0002-4800-6132; Raffel, Owen C/0000-0001-5470-7050; Muenzel, Thomas/0000-0001-5503-4150; Ersanli, Murat/0000-0003-1847-3087; Gislason, Gunnar H/0000-0002-0548-402X; bastos, jose/0000-0002-9526-3123; Abbate, Antonio/0000-0002-1930-785X; Chumakova, Galina A/0000-0002-2810-6531; Nikolaev, Konstantin/0000-0003-4601-6203; Tse, Hung Fat/0000-0002-9578-7808; Keskin, Kudret/0000-0002-9049-1530; Reshetko, Olga/0000-0003-3107-7636; Podoleanu, Cristian/0000-0001-9987-2519; Aylward, Philip/0000-0002-5358-8552; LETIERCE, Alexia/0000-0001-6679-5772, WOS: 000483334800002, PubMed: 31466614, BACKGROUND Patients with acute coronary syndrome (ACS) and history of coronary artery bypass grafting (CABG) are at high risk for recurrent cardiovascular events and death. OBJECTIVES This study sought to determine the clinical benefit of adding alirocumab to statins in ACS patients with prior CABG in a pre-specified analysis of ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab). METHODS Patients (n = 18,924) 1 to 12 months post-ACS with elevated atherogenic lipoprotein levels despite high-intensity statin therapy were randomized to alirocumab or placebo subcutaneously every 2 weeks. Median follow-up was 2.8 years. the primary composite endpoint of major adverse cardiovascular events (MACE) comprised coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint. Patients were categorized by CABG status: no CABG (n = 16,896); index CABG after qualifying ACS, but before randomization (n = 1,025); or CABG before the qualifying ACS (n = 1,003). RESULTS in each CABG category, hazard ratios (95% confidence intervals) for MACE (no CABG 0.86 [0.78 to 0.95], index CABG 0.85 [0.54 to 1.35], prior CABG 0.77 [0.61 to 0.98]) and death (0.88 [ 0.75 to 1.03], 0.85 [0.46 to 1.59], 0.67 [0.44 to 1.01], respectively) were consistent with the overall trial results (0.85 [ 0.78 to 0.93] and 0.85 [0.73 to 0.98], respectively). Absolute risk reductions (95% confidence intervals) differed across CABG categories for MACE (no CABG 1.3% [0.5% to 2.2%], index CABG 0.9% [-2.3% to 4.0%], prior CABG 6.4% [0.9% to 12.0%]) and for death (0.4% [-0.1% to 1.0%], 0.5% [-1.9% to 2.9%], and 3.6% [0.0% to 7.2%]). CONCLUSIONS Among patients with recent ACS and elevated atherogenic lipoproteins despite intensive statin therapy, alirocumab was associated with large absolute reductions in MACE and death in those with CABG preceding the ACS event. (ODYSSEY OUTCOMES: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402) (C) 2019 by the American College of Cardiology Foundation., Fondation Assistance Publique-Hopitaux de Paris, Paris, France, The authors thank the patients, study coordinators, and investigators who participated in this trial. Sophie Rushton-Smith, PhD (MedLink Healthcare Communications, London) provided editorial assistance in the preparation of the manuscript (limited to editing for style, referencing, and figure and table editing) and was funded by Fondation Assistance Publique-Hopitaux de Paris, Paris, France.

Published
2019

30. In‐situ data and effect correlation during September 2017 solar particle event

Author

Jiggens, P. (P.), Clavie, C. (C.), Evans, H. (H.), O’Brien, T. (T.P.), Witasse, O. (O.), Mishev, A. (A.L.), Nieminen, P. (P.), Daly, E. (E.), Kalegaev, V. (V.), Vlasova, N. (N.), Borisov, S. (S.), Benck, S. (S.), Poivey, C. (C.), Cyamukungu, M. (M.), Mazur, J. (J.), Heynderickx, D. (D.), Sandberg, I. (I.), Berger, T. (T.), Usoskin, I. (I.G.), Paassilta, M. (M.), Vainio, R. (R.), Straube, U. (U.), Müller, D. (D.), Sánchez-Cano, B. (B.), Hassler, D. (D.), Praks, J. (J.), Niemelä, P. (P.), Leppinen, H. (H.), Punkkinen, A. (A.), Aminalragia-Giamini, S. (S.), and Nagatsuma, T. (T.)

Subjects
radiation, SEEs, SEP, GLE, Physics::Space Physics, dose, SPE
Abstract

Solar energetic particles are one of the main sources of particle radiation seen in space. In the first part of September 2017 the most active solar period of cycle 24 produced four large X‐class flares and a series of (interplanetary) coronal mass ejections, which gave rise to radiation storms seen over all energies and at the ground by neutron monitors. This paper presents comprehensive cross comparisons of in situ radiation detector data from near‐Earth satellites to give an appraisal on the state of present data processing for monitors of such particles. Many of these data sets have been the target of previous cross calibrations, and this event with a hard spectrum provides the opportunity to validate these results. As a result of the excellent agreement found between these data sets and the use of neutron monitor data, this paper also presents an analytical expression for fluence spectrum for the event. Derived ionizing dose values have been computed to show that although there is a significant high‐energy component, the event was not particularly concerning as regards dose effects in spacecraft electronics. Several sets of spacecraft data illustrating single event effects are presented showing a more significant impact in this regard. Such a hard event can penetrate thick shielding; human dose quantities measured inside the International Space Station and derived through modeling for aircraft altitudes are also presented. Lastly, simulation results of coronal mass ejection propagation through the heliosphere are presented along with data from Mars‐orbiting spacecraft in addition to data from the Mars surface.

Published
2019

31. Effect of Alirocumab on Mortality After Acute Coronary Syndromes An Analysis of the ODYSSEY OUTCOMES Randomized Clinical Trial

Author

Steg, PG, Szarek, M, Bhatt, DL, Bittner, VA, Bregeault, M-F, Dalby, AJ, Diaz, R, Edelberg, JM, Goodman, SG, Hanotin, C, Harrington, RA, Jukema, JW, Lecorps, G, Mahaffey, KW, Moryusef, A, Ostadal, P, Parkhomenko, A, Pordy, R, Roe, MT, Tricoci, P, Vogel, R, White, HD, Zeiher, AM, Schwartz, GG, Sasiela, WJ, Tamby, J-F, Aylward, PE, Drexel, H, Sinnaeve, P, Dilic, M, Gotcheva, NN, Prieto, J-C, Yong, H, Lopez-Jaramillo, P, Pecin, I, Reiner, Z, Poulsen, SH, Viigimaa, M, Nieminen, MS, Danchin, N, Chumburidze, V, Marx, N, Liberopoulos, E, Valdovinos, PCM, Tse, H-F, Kiss, RG, Xavier, D, Zahger, D, Valgimigli, M, Kimura, T, Kim, HS, Kim, S-H, Kedev, S, Erglis, A, Laucevicius, A, Yusoff, K, Lopez, R, Ramos Lopez, GA, Alings, M, Halvorsen, S, Correa Flores, RM, Sy, RG, Budaj, A, Morais, J, Dorobantu, M, Karpov, Y, Ristic, AD, Chua, T, Murin, J, Fras, Z, Tunon, J, De Silva, HA, Hagstrom, E, Muller, C, Chiang, C-E, Sritara, P, Guneri, S, Ray, KK, Moriarty, PM, Chaitman, B, Kelsey, SF, Olsson, AG, Rouleau, J-L, Simoons, ML, Alexander, K, Meloni, C, Rosenson, R, Sijbrands, EJG, Alexander, JH, Armaganijan, L, Bagai, A, Bahit, MC, Brennan, JM, Clifton, S, DeVore, AD, Deloatch, S, Dickey, S, Dombrowski, K, Ducrocq, G, Eapen, Z, Endsley, P, Eppinger, A, Harrison, RW, Hess, CN, Hlatky, MA, Jordan, JD, Knowles, JW, Kolls, BJ, Kong, DF, Leonardi, S, Lillis, L, Maron, DJ, Marcus, J, Mathews, R, Mehta, RH, Mentz, RJ, Moreira, HG, Patel, CB, Pereira, SB, Perkins, L, Povsic, TJ, Puymirat, E, Jones, WS, Shah, BR, Sherwood, MW, Stringfellow, K, Sujjavanich, D, Toma, M, Van Diepen, SFP, Wilson, MD, Yan, AT-K, Lopes, RD, Trotter, C, Schiavi, LB, Garrido, M, Alvarisqueta, AF, Sassone, SA, Bordonava, AP, Alves De Lima, AE, Schmidberg, JM, Duronto, EA, Caruso, OC, Novaretto, LP, Angel Hominal, M, Montana, OR, Caccavo, A, Gomez Vilamajo, OA, Lorenzatti, AJ, Cartasegna, LR, Paterlini, GA, Mackinnon, IJ, Caime, GD, Amuchastegui, M, Salomone, R, Codutti, OR, Jure, HO, Bono, JOE, Hrabar, AD, Vallejos, JA, Ahuad Guerrero, RA, Novoa, F, Patocchi, CA, Zaidman, CJ, Giuliano, ME, Dran, RD, Vico, ML, Carnero, GS, Guzman, PN, Medrano Allende, JC, Garcia Brasca, DF, Bustamante Labarta, MH, Nani, S, Blumberg, EDS, Colombo, HR, Liberman, A, Luciardi, HL, Waisman, GD, Berli, MA, Duran, ROG, Cestari, HG, Luquez, HA, Giordano, JA, Saavedra, SS, Zapata, G, Costamagna, O, Llois, S, Waites, JH, Collins, N, Soward, A, Hii, CLS, Shaw, J, Arstall, MA, Horowitz, J, Rogers, JF, Colquhoun, D, Oqueli Flores, RE, Roberts-Thomson, P, Raffel, O, Lehman, SJ, Aroney, C, Coverdale, SGM, Garrahy, PJ, Starmer, G, Sader, M, Carroll, PA, Dick, R, Zweiker, R, Hoppe, U, Huber, K, Berger, R, Weidinger, F, Faes, D, Hermans, K, Pirenne, B, Leone, A, Hoffer, E, Vrolix, MCM, De Wolf, L, Wollaert, B, Castadot, M, Dujardin, K, Beauloye, C, Vervoort, G, Striekwold, H, Convens, C, Roosen, J, Barbato, E, Claeys, M, Cools, F, Terzic, I, Barakovic, F, Midzic, Z, Pojskic, B, Fazlibegovic, E, Durak-Nalbantic, A, Vulic, D, Muslibegovic, A, Goronja, B, Reis, G, Sousa, L, Nicolau, JC, Giorgeto, FE, Silva, RP, Maia, LN, Rech, R, Rossi, PRF, Cerqueira, MJAG, Duda, N, Kalil, R, Kormann, A, Abrantes, JAM, Pimentel Filho, P, Soggia, AP, De Santos, MON, Neuenschwander, F, Bodanese, LC, Michalaros, YL, Eliaschewitz, FG, Vidotti, MH, Leaes, PE, Botelho, RV, Kaiser, S, Fernandes Manenti, ERF, Precoma, DB, Moura Jorge, JC, Silva, PGMDB, Silveira, JA, Saporito, W, Marin Neto, JA, Feitosa, GS, Ritt, LEF, De Souza, JA, Costa, F, Souza, WKSB, Reis, HJL, Machado, L, Aidar Ayoub, JC, Todorov, GV, Nikolov, FP, Velcheva, ES, Tzekova, ML, Benov, HO, Petranov, SL, Tumbev, HS, Shehova-Yankova, NS, Markov, DT, Raev, DH, Mollov, MN, Kichukov, KN, Ilieva-Pandeva, KA, Ivanova, R, Mincheva, VM, Lazov, PV, Dimov, BI, Senaratne, M, Stone, J, Kornder, J, Pearce, S, Dion, D, Savard, D, Pesant, Y, Pandey, A, Robinson, S, Gosselin, G, Vizel, S, Hoag, G, Bourgeois, R, Morisset, A, Sabbah, E, Sussex, B, Kouz, S, MacDonald, P, Diaz, A, Michaud, N, Fell, D, Leung, R, Vuurmans, T, Lai, C, Nigro, F, Davies, R, Nogareda, G, Vijayaraghavan, R, Ducas, J, Lepage, S, Mehta, S, Cha, J, Dupuis, R, Fong, P, Rodes-Cabau, J, Fadlallah, H, Cleveland, D, Thao, H, Bata, I, Hameed, A, Pincetti, C, Potthoff, S, Prieto, JC, Acevedo, M, Aguirre, A, Vejar, M, Yanez, M, Araneda, G, Fernandez, M, Perez, L, Varleta, P, Florenzano, F, Huidobro, L, Raffo, CA, Olivares, C, Nahuelpan, L, Montecinos, H, Chen, J, Dong, Y, Huang, W, Wang, J, Huang, S, Yao, Z, Li, X, Cui, L, Lin, W, Sun, Y, Li, J, Zhang, X, Zhu, H, Chen, D, Huang, L, Dong, S, Su, G, Xu, B, Su, X, Cheng, X, Lin, J, Zong, W, Li, H, Feng, Y, Xu, D, Yang, X, Ke, Y, Lin, X, Zhang, Z, Zheng, Z, Luo, Z, Chen, Y, Ding, C, Zheng, Y, Peng, D, Li, Y, Wei, M, Liu, S, Yu, Y, Qu, B, Jiang, W, Zhou, Y, Zhao, X, Yuan, Z, Guo, Y, Xu, X, Shi, X, Ge, J, Fu, G, Bai, F, Fang, W, Shou, X, Lu, Q, Zhang, R, Zhu, J, Xu, Y, Fan, Z, Li, T, Wu, C, Jaramillo, N, Vallejo, GS, Botia, DCL, Lopez, RB, De Salazar, DIM, Bonfanti, AJC, Higuera, JD, Silva, SIB, Lozada, HJG, Arroyo, JAC, Mendoza, JLA, Ruiz, RLF, Jatin, FGM, Herazo, AS, Parada, JC, Triana, MAU, Strozzi, M, Car, S, Milicic, D, Bencic, ML, Pintaric, H, Prvulovic, D, Sikic, J, Persic, V, Mileta, D, Stambuk, K, Zdravko, B, Tomulic, V, Krstulovic, SM, Starcevic, B, Spinar, J, Horak, D, Stasek, J, Alan, D, Machova, V, Linhart, A, Novotny, V, Kaucak, V, Rokyta, R, Naplava, R, Coufal, Z, Adamkova, V, Podpera, I, Zizka, J, Motovska, Z, Marusincova, I, Svab, P, Heinc, P, Kuchar, J, Povolny, P, Matuska, J, Raungaard, B, Clemmensen, P, Bang, LE, May, O, Bottcher, M, Hove, JD, Frost, L, Gislason, G, Larsen, J, Johansen, PB, Hald, F, Jeppesen, J, Nielsen, T, Kristensen, KS, Walichiewicz, PM, Lomholdt, JD, Klausen, IC, Nielsen, PK, Davidsen, F, Videbaek, L, Soots, M, Vahula, V, Hedman, A, Soopold, U, Martsin, K, Kristjan, A, Taskinen, M-R, Porthan, K, Airaksinen, JK, Juonala, M, Kiviniemi, T, Vikman, S, Posio, P, Taurio, J, Huikuri, H, Kaikkonen, K, Coste, P, Ferrari, E, Morel, O, Montalescot, G, Barone-Rochette, G, Mansourati, J, Cottin, Y, Leclercq, F, Belhassane, A, Delarche, N, Boccara, F, Paganelli, F, Clerc, J, Schiele, F, Aboyans, V, Probst, V, Berland, J, Lefevre, T, Citron, B, Khintibidze, I, Shaburishvili, T, Pagava, Z, Ghlonti, R, Lominadze, Z, Khabeishvili, G, Hemetsberger, R, Rauch-Kroehnert, U, Stratmann, M, Appel, K-F, Schmidt, E, Omran, H, Stellbrink, C, Dorsel, T, Lianopoulos, E, Marx, R, Zirlik, A, Schellenberg, D, Heitzer, T, Laufs, U, Gielen, S, Winkelmann, B, Behrens, S, Sydow, K, Simonis, G, Muenzel, T, Werner, N, Leggewie, S, Boecker, D, Braun-Dullaeus, R, Toursarkissian, N, Jeserich, M, Weissbrodt, M, Schaeufele, T, Weil, J, Voeller, H, Waltenberger, J, Natour, M, Schmitt, S, Steiner, S, Heidenreich, L, Gremmler, U, Killat, H, Rieker, W, Patsilinakos, S, Kartalis, A, Manolis, A, Sionis, D, Skoumas, I, Athyros, V, Vardas, P, Parthenakis, F, Alexopoulos, D, Hahalis, G, Lekakis, J, Hatzitolios, A, Ovando, SRF, Benecke, JLA, De Leon, ERR, Yan, BPY, Siu, DCW, Turi, T, Merkely, B, Ungi, I, Lupkovics, G, Nagy, L, Katona, A, Edes, I, Muller, G, Horvath, I, Kapin, T, Falukozy, J, Kumbla, M, Sandhu, M, Annam, S, Proddutur, NR, Premchand, RK, Mahajan, A, Abhyanakar, AD, Kerkar, P, Govinda, RA, Oomman, A, Sinha, D, Patil, SN, Kahali, D, Sawhney, J, Joshi, AB, Chaudhary, S, Harkut, P, Guha, S, Porwal, S, Jujjuru, S, Pothineni, RB, Monteiro, MR, Khan, A, Iyengar, SS, Grewal, JS, Chopda, M, Fulwani, MC, Patange, A, Chopra, VK, Goyal, NK, Shinde, R, Manakshe, GV, Patki, N, Sethi, S, Munusamy, V, Karna, S, Adhyapak, S, Pandurangi, U, Mathur, R, Kalashetti, S, Bhagwat, A, Raghuraman, B, Yerra, SK, Bhansali, P, Borse, R, Das, S, Abdullakutty, J, Saathe, S, Palimkar, P, Abdullkutty, J, Sathe, S, Atar, S, Shechter, M, Mosseri, M, Arbel, Y, Lotan, C, Rosenschein, U, Katz, A, Henkin, Y, Francis, A, Klutstein, M, Nikolsky, E, Turgeman, Y, Halabi, M, Kornowski, R, Jonas, M, Amir, O, Rozenman, Y, Fuchs, S, Hussein, O, Gavish, D, Vered, Z, Caraco, Y, Elias, M, Tov, N, Lishner, M, Elias, N, Piovaccari, G, De Pellegrin, A, Guardigli, G, Licciardello, G, Auguadro, C, Cuccia, C, Salvioni, A, Musumeci, G, Calabro, P, Novo, S, Faggiano, P, De Cesare, NB, Berti, S, Cavallini, C, Puccioni, E, Galvani, M, Tespili, M, Piatti, P, Palvarini, M, De Luca, G, Violini, R, De Leo, A, Filardi, PP, Ferratini, M, Ricca, V, Dai, K, Kamiya, H, Ando, K, Takeda, Y, Morino, Y, Hata, Y, Kimura, K, Kishi, K, Michishita, I, Uehara, H, Higashikata, T, Hirayama, A, Hirooka, K, Sakagami, S, Taguchi, S, Koike, A, Fujinaga, H, Koba, S, Kozuma, K, Kawasaki, T, Ono, Y, Shimizu, M, Katsuda, Y, Wada, A, Shinke, T, Ako, J, Fujii, K, Takahashi, T, Sakamoto, T, Furukawa, Y, Sugino, H, Mano, T, Utsu, N, Ito, K, Haraguchi, T, Ueda, Y, Nishibe, A, Fujimoto, K, Masutani, M, Yoon, JH, Park, HS, Chae, I-H, Kim, MH, Jeong, MH, Rha, S, Kim, C, Kim, H-S, Hong, T, Tahk, S-J, Kim, Y, Busmane, A, Pontaga, N, Strelnieks, A, Mintale, I, Sime, I, Petrulioniene, Z, Kavaliauskiene, R, Jurgaitiene, R, Sakalyte, G, Slapikas, R, Norkiene, S, Misonis, N, Kibarskis, A, Kubilius, R, Bojovski, S, Lozance, N, Kjovkaroski, A, Doncovska, S, Ong, TK, Kasim, S, Maskon, O, Kandasamy, B, Liew, HB, Mohamed, WMIW, Garcia Castillo, A, Carrillo Calvillo, J, Fajardo Campos, P, Nunez Fragoso, JC, Bayram Llamas, EA, Alcocer Gamba, MA, Carranza Madrigal, J, Gonzalez Salas, LG, Lopez Rosas, E, Gonzalez Diaz, B, Salcido Vazquez, E, Nacoud Ackar, A, Llamas Esperon, GA, Martinez Sanchez, CR, Guerrero De Leon, M, Suarez Otero, R, Fanghanel Salmon, G, Perez Rios, JA, Garza Ruiz, JA, Breedveld, RW, Hoogslag, PAM, Suryapranata, H, Oomen, A, Wiersma, JJ, Van Der Wal, RMA, Van Huysduynen-Monraats, PSH, Karalis, I, Verdel, GJE, Brueren, BRG, Troquay, RP, Viergever, EP, Al-Windy, NYY, Bartels, GL, Cornel, JH, Hermans, WRM, Herrman, JPR, Bos, RJ, Groutars, RGEJ, Van Der Zwaan, CC, Kaplan, R, Ronner, E, Groenemeijer, BE, Bronzwaer, PNA, Liem, AAH, Rensing, BJWM, Bokern, MJJA, Nijmeijer, R, Hersbach, FMRJ, Willems, FF, Gosselink, ATM, Elliott, J, Wilkins, G, Fisher, R, Scott, D, Hart, H, Stewart, R, Harding, S, Ternouth, I, Fisher, N, Aitken, D, Anscombe, R, Davidson, L, Tomala, T, Nygard, O, Sparby, JA, Andersen, K, Gullestad, L, Jortveit, J, Munk, PS, Singsaas, EG, Hurtig, U, Calderon Ticona, JR, Durand Velasquez, JR, Negron Miguel, SA, Sanabria Perez, ES, Carrion Chambilla, JM, Chavez Ayala, CA, Castillo Leon, RP, Vargas Gonzales, RJ, Hernandez Zuniga, JD, Camacho Cosavalente, LA, Bravo Mannucci, JE, Heredia Landeo, J, Llerena Navarro, NC, Roldan Concha, YM, Rodriguez Chavez, V-CE, Anchante Hernandez, HA, Zea Nunez, CA, Mogrovejo Ramos, W, Ferrolino, A, Sy, RAG, Tirador, L, Matiga, G, Coching, RM, Bernan, A, Rogelio, G, Morales, DD, Tan, E, Sulit, DJ, Wlodarczak, A, Jaworska, K, Skonieczny, G, Pawlowicz, L, Wojewod, P, Busz-Papiez, B, Bednarski, J, Goch, A, Staneta, P, Dulak, E, Saminsk, K, Krasowski, W, Sudnik, W, Zurakowski, A, Skorski, M, Lysek, R, Miklaszewicz, B, Kubica, J, Lipko, JA, Kostarska-Srokosz, E, Piepiorka, M, Drzewiecka, A, Sciborski, R, Stasiewski, A, Blicharski, T, Bystryk, L, Szpajer, M, Korol, M, Czerski, T, Mirek-Bryniarska, E, Gniot, J, Lubinski, A, Gorny, J, Franek, E, Raczak, G, Szwed, H, Monteiro, P, Bastos, JM, Pereira, HH, Martins, D, Seixo, F, Mendonca, C, Botelho, A, Minescu, B, Istratoaie, O, Tesloianu, DN, Cristian, G, Podoleanu, CGC, Constantinescu, MCA, Bengus, CM, Militaru, C, Rosu, D, Parepa, IR, Matei, AV, Alexandru, TM, Coman, I, Cioranu, RS, Dimulescu, D, Shvarts, Y, Orlikova, O, Kobalava, Z, Barbarash, OL, Markov, V, Lyamina, N, Gordienko, A, Zrazhevsky, K, Vishnevsky, AY, Gurevich, V, Stryuk, R, Lomakin, NV, Bokarev, I, Shalaev, S, Khaisheva, L, Chizhov, P, Viktorova, I, Osokina, N, Akatova, E, Chumakova, G, Libov, I, Voevoda, MI, Tretyakova, TV, Baranov, E, Shustov, S, Yakushin, S, Gordeev, I, Khasanov, N, Reshetko, O, Sotnikova, T, Molchanova, O, Nikolaev, K, Gapon, L, Baranova, E, Shogenov, Z, Kosmachova, E, Povzun, A, Egorova, L, Tyrenko, VV, Ivanov, IG, Kanorsky, S, Simic, D, Ivanovic, N, Davidovic, G, Tasic, N, Asanin, MR, Stojic, S, Apostolovic, SR, Ilic, S, Putnikovic, B, Stankovic, A, Arandjelovic, A, Radovanovic, S, Balinovac, J, Dincic, DV, Seferovic, P, Dodic, S, Dimkovic, S, Poh, K-K, Ong, HY, Micko, K, Nociar, J, Pella, D, Fulop, P, Hranai, M, Palka, J, Mazur, J, Majercak, I, Dzupina, A, Fazekas, F, Gonsorcik, J, Bugan, V, Selecky, J, Kamensky, G, Strbova, J, Smik, R, Dukat, A, Olexa, P, Zuran, I, Poklukar, J, Suligoj, NC, Cevc, M, Cyster, HP, Ranjith, N, Corbett, C, Bayat, J, Makotoko, EM, Kapp, IE, Basson, MMDV, Lottering, H, Van Zyl, LJ, Sebastian, PJ, Pillay, T, Saaiman, JA, Commerford, PJ, Cassimjee, S, Ebrahim, IO, Sarvan, M, Mynhardt, JH, Reuter, H, Moodley, R, Vida, M, Cequier Fillat, AR, Peris, VB, Jimenez, FF, Marin, F, Cruz Fernandez, JM, Gil-Extremera, B, Diz, FW, Garcia-Dorado, D, Iniguez, A, Tunon Fernandez, J, 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Mclaurin, B, Zhang, W, Thew, S, Abbas, J, White, M, Ranadive, N, Gring, C, Henderson, D, Schuchard, T, Farhat, N, Kline, G, Mahal, S, Whitaker, J, Speirs, S, Andersen, R, Daboul, N, Horwitz, P, Ponce, G, Jafar, Z, Mcgarvey, J, Panchal, V, Voyce, S, Blok, T, Sheldon, W, Azizad, MM, Schmalfuss, C, Picone, M, Herzog, W, Lindsey, J, Nowins, R, Lepor, N, El Shahawy, M, Weintraub, H, Irimpen, A, May, W, Galski, T, Chu, A, Mody, F, Hodes, Z, Rose, G, Fairlamb, J, Lambert, C, Raisinghani, A, Abbate, A, King, M, Carey, C, Gerber, J, Younis, L, Park, HT, Vidovich, M, Knutson, T, Friedman, D, Chaleff, F, Loussararian, A, Rozeman, P, Kimmelstiel, C, Silver, K, Foster, M, Tonnessen, G, Amlani, M, Wali, A, Malozzi, C, Wattanakit, K, O'Donnell, PJ, Singal, D, Jaffrani, N, Banuru, S, Fisher, D, Xenakis, M, Perlmutter, N, Bhagwat, R, Strader, J, Akyea-Djamson, A, Labroo, A, Marais, HJ, Claxton, E, Berk, M, Rossi, P, Joshi, P, Khaira, AS, Kumkumian, G, Lupovitch, S, Purow, J, Welka, S, Hoffman, D, Fischer, S, Soroka, E, Eagerton, D, Pancholy, S, Ray, M, Farrar, M, Pollock, S, French, WJ, Diamantis, S, Gimple, L, Neustel, M, Schwartz, S, Pereira, E, Spriggs, D, Strain, J, Vo, A, Chane, M, Hall, J, Vijay, N, Lotun, K, Lester, FM, Nahhas, A, Pope, T, Nager, P, Vohra, R, Bashir, R, Ahmed, H, Berlowitz, M, Fishberg, R, Barrucco, R, Yang, E, Radin, M, Sporn, D, Eisenberg, S, Landzberg, J, Mcgough, M, Turk, S, Schwartz, M, Sundram, PS, Jain, D, Zainea, M, Bayron, C, Karlsberg, R, Lui, H, Keen, W, Westerhausen, D, Khurana, S, Agarwal, H, Birchem, J, Penny, W, Chang, M, Murphy, S, Schifferdecker, B, Gilbert, JM, Chalavarya, G, Eaton, C, Schmedtje, JF, Christenson, S, Denham, D, Macdonell, A, Gibson, P, Rahman, A, Al Joundi, T, Conrad, G, Kotha, P, Love, M, Giesler, G, Rubenstein, H, Akright, L, Krawczyk, J, Wells, T, Welker, J, Foster, R, Gilmore, R, Anderson, J, Jacoby, D, Gardner, G, Dandillaya, R, Vora, K, Kostis, J, Hunter, J, Laxson, D, Ball, E, Camp, A, Lopes, R, Egydio, F, Kawakami, A, Oliveira, J, Wozniak, J, Matthews, A, Ratky, C, Valiris, J, Berdan, L, Hepditch, A, Quintero, K, Rorick, T, Westbrook, M, Pascual, A, Rovito, C, Bezault, M, Drouet, E, Simon, T, Alsweiler, C, Luyten, A, Aylward, P, Butters, J, Griffith, L, Shaw, M, Grunberg, L, Islam, S, Bougon, N, Faustino, D, Fontecave, S, Murphy, J, Verrier, M, Agnetti, V, Andersen, D, Badreddine, E, Bekkouche, M, Bouancheau, C, Brigui, I, Brocklehurst, M, Cianciarulo, J, Devaul, D, Domokos, S, Gache, C, Gobillot, C, Guillou, S, Healy, J, Heath, M, Jaiwal, G, Javierre, C, Labeirie, J, Monier, M, Morales, U, Mrabti, A, Mthombeni, B, Okan, B, Smith, L, Sheller, J, Sopena, S, Pellan, V, Benbernou, F, Bengrait, N, Lamoureux, M, Kralova, K, Scemama, M, Bejuit, R, Coulange, A, Berthou, C, Repincay, J, Lorenzato, C, Etienne, A, Gouet, V, Loizeau, V, Normand, M, Ourliac, A, Rondel, C, Adamo, A, Beltran, P, Barraud, P, Dubois-Gache, H, Halle, B, Metwally, L, Mourgues, M, Sotty, M, Vincendet, M, Cotruta, R, Zhu, C, Fournie-Lloret, D, Morrello, C, Perthuis, A, Picault, P, Zobouyan, I, ODYSSEY OUTCOMES Comm, İÜC, Ege Üniversitesi, Rushton-Smith, Sophie, and ODYSSEY OUTCOMES Committees and Investigators

Subjects
Male, Cardiac & Cardiovascular Systems, MONOCLONAL-ANTIBODY, alirocumab, Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage, law.invention, PCSK9, chemistry.chemical_compound, Randomized controlled trial, law, Cardiac and Cardiovascular Systems, 1102 Cardiorespiratory Medicine and Haematology, Hypercholesterolemia/blood, Kardiologi, Hazard ratio, Middle Aged, Treatment Outcome, SAFETY, Cardiology, Female, Drug Therapy, Combination, Cholesterol, LDL/antagonists & inhibitors, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, REDUCING LIPIDS, Akutes Koronarsyndrom, acute coronary syndrome, cholesterol, mortality, PCSK9 protein, Antibodies, Monoclonal, Humanized/administration & dosage, medicine.medical_specialty, Acute coronary syndrome, Injections, Subcutaneous, Hypercholesterolemia, Placebo, Antibodies, Monoclonal, Humanized, 1117 Public Health and Health Services, Sterblichkeit, Double-Blind Method, Physiology (medical), Internal medicine, medicine, Humans, ddc:610, Alirocumab, Aged, Science & Technology, Cholesterol, business.industry, EVOLOCUMAB, 1103 Clinical Sciences, Cholesterol, LDL, medicine.disease, EFFICACY, Increased risk, chemistry, Peripheral Vascular Disease, Cardiovascular System & Hematology, Cardiovascular System & Cardiology, Acute Coronary Syndrome/blood, Cholesterin, Human medicine, Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, Follow-Up Studies
Abstract

bastos, jose/0000-0002-9526-3123; Manakshe, Gajendra/0000-0002-4983-4271; Tse, Hung Fat/0000-0002-9578-7808; Gislason, Gunnar H/0000-0002-0548-402X; Taskinen, Marja-Riitta/0000-0002-6229-3588; Racca, Vittorio/0000-0002-4465-3789; Keskin, Kudret/0000-0002-9049-1530; Sherwood, Matthew/0000-0002-4305-5883; Sandhu, Manjinder/0000-0003-2538-2079; Nikolaev, Konstantin/0000-0003-4601-6203; Ersanli, Murat/0000-0003-1847-3087; Raffel, Owen C/0000-0001-5470-7050; Abbate, Antonio/0000-0002-1930-785X; Muenzel, Thomas/0000-0001-5503-4150; Leonardi, Sergio/0000-0002-4800-6132; Chumakova, Galina A/0000-0002-2810-6531; Podoleanu, Cristian/0000-0001-9987-2519; Pereira, Helder/0000-0001-8656-4883; Reshetko, Olga/0000-0003-3107-7636, WOS: 000476768100007, PubMed: 31117810, Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. in a prespecified analysis of 8242 patients eligible for >= 3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P= 100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; P-interaction=0.007). in the alirocumab group, all-cause death declined with achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for >= 3 years, if baseline LDL-C is >= 100 mg/dL, or if achieved LDL-C is low., Sanofi; Regeneron Pharmaceuticals, Inc., The trial was funded by Sanofi and Regeneron Pharmaceuticals, Inc.

Published
2019

32. Alirocumab Reduces Total Hospitalizations and Increases Days Alive and Out of Hospital in the ODYSSEY OUTCOMES Trial

Author

DiCenso, D, Gotcheva, N, Sourdille, T, White, HD, Schwartz, GG, Steg, PG, Bhatt, DL, Bittner, VA, Diaz, R, Harrington, RA, Jukema, JW, Szarek, M, Zeiher, AM, Tricoci, P, Mahaffey, KW, Edelberg, JM, Hanotin, C, Lecorps, G, Moryusef, A, Pordy, R, Sasiela, WJ, Drexel, H, Sinnaeve, P, Dilic, M, Gotcheva, NN, Goodman, SG, Prieto, JC, Yong, H, Lopez-Jaramillo, P, Pecin, I, Reiner, Z, Poulsen, SH, Viigimaa, M, Nieminen, MS, Danchin, N, Chumburidze, V, Tse, HF, Xavier, D, Zahger, D, Valgimigli, M, Kim, HS, Erglis, A, Laucevicius, A, Lopez, R, Lopez, GAR, Alings, M, Chua, T, Murin, J, Fras, Z, Dalby, AJ, Tunon, J, De Silva, HA, Chiang, CE, Sritara, P, Guneri, S, Parkhomenko, A, Ray, KK, Moriarty, PM, Roe, MT, Chaitman, B, Kelsey, SF, Olsson, AG, Rouleau, JL, Simoons, ML, Alexander, K, Meloni, C, Rosenson, R, Sijbrands, EJG, Alexander, JH, Armaganijan, L, Bagai, A, Bahit, MC, Brennan, JM, Clifton, S, DeVore, AD, Deloatch, S, Dickey, S, Dombrowski, K, Ducrocq, G, Eapen, Z, Endsley, P, Eppinger, A, Harrison, RW, Hess, CN, Hlatky, MA, Jordan, JD, Knowles, JW, Kolls, BJ, Kong, DF, Leonardi, S, Lillis, L, Maron, DJ, Marcus, J, Mathews, R, Mehta, RH, Mentz, RJ, Moreira, HG, Patel, CB, Pereira, SB, Perkins, L, Povsic, TJ, Puymirat, E, Jones, WS, Shah, BR, Sherwood, MW, Stringfellow, K, Sujjavanich, D, Toma, M, Van Diepen, SFP, Wilson, MD, Yan, ATK, Lopes, RD, Trotter, C, Schiavi, LB, Garrido, M, Alvarisqueta, AF, Sassone, SA, Bordonava, AP, De Lima, AEA, Schmidberg, JM, Duronto, EA, Caruso, OC, Novaretto, LP, Hominal, MA, Montana, OR, Caccavo, A, Vilamajo, OAG, Lorenzatti, AJ, Cartasegna, LR, Paterlini, GA, Mackinnon, IJ, Caime, GD, Amuchastegui, M, Salomone, R, Codutti, OR, Jure, HO, Bono, JOE, Hrabar, AD, Vallejos, JA, Guerrero, RAA, Novoa, F, Patocchi, CA, Zaidman, CJ, Giuliano, ME, Dran, RD, Vico, ML, Carnero, GS, Guzman, PN, Allende, JCM, Brasca, DFG, Labarta, MHB, Nani, S, Blumberg, EDS, Colombo, HR, Liberman, A, Luciardi, HL, Waisman, GD, Berli, MA, Duran, ROG, Cestari, HG, 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A, King, M, Carey, C, Gerber, J, Younis, L, Park, H, Vidovich, M, Knutson, T, Friedman, D, Chaleff, F, Loussararian, A, Rozeman, P, Kimmelstiel, C, Silver, K, Foster, M, Tonnessen, G, Amlani, M, Wali, A, Malozzi, C, Wattanakit, K, O'Donnell, PJ, Singal, D, Jaffrani, N, Banuru, S, Fisher, D, Xenakis, M, Perlmutter, N, Bhagwat, R, Strader, J, Akyea-Djamson, A, Labroo, A, Marais, HJ, Claxton, E, Berk, M, Rossi, P, Joshi, P, Khaira, AS, Kumkumian, G, Lupovitch, S, Purow, J, Welka, S, Hoffman, D, Fischer, S, Soroka, E, Eagerton, D, Pancholy, S, Ray, M, Farrar, M, Pollock, S, French, WJ, Diamantis, S, Gimple, L, Neustel, M, Schwartz, S, Pereira, E, Spriggs, D, Strain, J, Vo, A, Chane, M, Hall, J, Vijay, N, Lotun, K, Lester, FM, Nahhas, A, Pope, T, Nager, P, Vohra, R, Bashir, R, Ahmed, H, Berlowitz, M, Fishberg, R, Barrucco, R, Yang, E, Radin, M, Sporn, D, Eisenberg, S, Landzberg, J, Mcgough, M, Turk, S, Schwartz, M, Sundram, PS, Jain, D, Zainea, M, Bayron, C, Karlsberg, R, Lui, H, Keen, W, 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Domokos, S, Gache, C, Gobillot, C, Guillou, S, Healy, J, Heath, M, Jaiwal, G, Javierre, C, Labeirie, J, Monier, M, Morales, U, Mrabti, A, Mthombeni, B, Okan, B, Smith, L, Sheller, J, Sopena, S, Pellan, V, Benbernou, F, Bengrait, N, Lamoureux, M, Kralova, K, Scemama, M, Bejuit, R, Coulange, A, Berthou, C, Repincay, J, Lorenzato, C, Etienne, A, Gouet, V, Loizeau, V, Normand, M, Ourliac, A, Rondel, C, Adamo, A, Beltran, P, Barraud, P, Dubois-Gache, H, Halle, B, Metwally, L, Mourgues, M, Sotty, M, Vincendet, M, Cotruta, R, Zhu, CY, Fournie-Lloret, D, Morrello, C, Perthuis, A, Picault, P, Zobouyan, I, ODYSSEY OUTCOMES Comm Inve, Ege Üniversitesi, Cardiology, and Internal Medicine

Subjects
medicine.medical_specialty, Acute coronary syndrome, Time Factors, acute coronary syndrome, alirocumab, global burden of disease, hospitalization, myocardial infarction, PCSK9, 030204 cardiovascular system & hematology, Antibodies, Monoclonal, Humanized, Placebo, Patient Readmission, Risk Assessment, 03 medical and health sciences, Patient Admission, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Angina, Unstable, Hospital Mortality, 030212 general & internal medicine, Myocardial infarction, 03.02. Klinikai orvostan, Dyslipidemias, Alirocumab, Out of hospital, business.industry, Anticholesteremic Agents, Cholesterol, HDL, Cholesterol hdl, Cholesterol, LDL, medicine.disease, Treatment Outcome, Drug Therapy, Combination, Human medicine, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiology and Cardiovascular Medicine, business, Cardiovascular outcomes, Biomarkers
Abstract

Sherwood, Matthew/0000-0002-4305-5883; Abbate, Antonio/0000-0002-1930-785X; Moris, Cesar/0000-0002-2871-190X; Ersanli, Murat/0000-0003-1847-3087; Taskinen, Marja-Riitta/0000-0002-6229-3588; bastos, jose/0000-0002-9526-3123; Reshetko, Olga/0000-0003-3107-7636; Nikolaev, Konstantin/0000-0003-4601-6203; Leonardi, Sergio/0000-0002-4800-6132; Raffel, Owen C/0000-0001-5470-7050; Racca, Vittorio/0000-0002-4465-3789; Podoleanu, Cristian/0000-0001-9987-2519; Gislason, Gunnar H/0000-0002-0548-402X; Muenzel, Thomas/0000-0001-5503-4150; Tse, Hung Fat/0000-0002-9578-7808; Chumakova, Galina A/0000-0002-2810-6531, WOS: 000502609000004, PubMed: 31707826, Background: in ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), alirocumab was compared with placebo, added to high-intensity or maximum tolerated statin treatment after acute coronary syndrome in 18924 patients. Alirocumab reduced first occurrence of the primary composite end point-coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or hospitalization for unstable angina-as well as total nonfatal cardiovascular events and all-cause deaths. the present analysis determined whether alirocumab reduced total (first and subsequent) hospitalizations and death and increased days alive and out of hospital (DAOH) and percent DAOH in ODYSSEY OUTCOMES. Methods and Results: in prespecified analyses, hazard functions for total hospitalizations and death were jointly estimated by a semiparametric model, while in post hoc analyses, DAOH and percent DAOH were compared between treatment groups with Poisson regression and one-inflated beta regression, respectively. With 16629 total hospitalizations and 726 deaths, 331 fewer hospitalizations, and 58 fewer deaths were observed with alirocumab compared with placebo, translating to 15.6 total hospitalizations or deaths avoided with alirocumab per 1000 patient-years of assigned treatment. Alirocumab reduced total hospitalizations (hazard ratio, 0.96 [95% CI, 0.92-1.00]; P=0.04) and increased DAOH relative to placebo (rate ratio, 1.003 [95% CI, 1.000-1.007]; P=0.05), primarily through a reduction in days dead (rate ratio, 0.847 [95% CI, 0.728-0.986]; P=0.03). Patients randomized to alirocumab were also more likely to survive to the end of the study without hospitalization (odds ratio, 1.06 [95% CI, 1.00-1.13]; P=0.03). Conclusions: Alirocumab reduced total hospitalizations with corresponding small increases in DAOH and percent DAOH. These outcomes provide alternative patient-centered metrics to capture the totality of alirocumab clinical efficacy after acute coronary syndrome. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01663402., Fondation Assistance Publique-Hopitaux de Paris, Paris, France, We thank the patients, study coordinators, and investigators who participated in this trial. Sophie Rushton-Smith, PhD (MedLink Healthcare Communications, London) provided editorial assistance in the preparation of the article (limited to editing for style, referencing, and figure and table editing) and was funded by Fondation Assistance Publique-Hopitaux de Paris, Paris, France.

Published
2019

33. Right to Access Information as a Collective-Based Approach to the GDPR’s Right to Explanation in European Law

Author

Mazur, J. (Johanna) and Mazur, J. (Johanna)

Abstract

This article presents a perspective which focuses on the right to access information as a mean to ensure a non-discriminatory character of algorithms by providing an alternative to the right to explanation implemented in the General Data Protection Regulation (GDPR). I adopt the evidence-based assumption that automated decision-making technologies have an inherent discriminatory potential. The example of a regulatory means which to a certain extent addresses this problem is the approach based on privacy protection in regard to the right to explanation. The Articles 13-15 and 22 of the GDPR provide individual users with certain rights referring to the automated decision-making technologies. However, the right to explanation not only may have a very limited impact, but it also focuses on individuals thus overlooking potentially discriminated groups. Because of this, the article offers an alternative approach on the basis of the right to access information. It explores the possibility of using this right as a tool to receive information on the algorithms determining automated decision-making solutions. Tracking an evolution of the interpretation of Article 10 of the Convention for the Protection of Human Right and Fundamental Freedoms in the relevant case law aims to illustrate how the right to access information may become a collective- based approach towards the right to explanation. I consider both, the potential of this approach, such as its more collective character e.g. due to the unique role played by the media and NGOs in enforcing the right to access information, as well as its limitations.

Published
2019
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34. Evolocumab and clinical outcomes in patients with cardiovascular disease

Author

Sabatine, Marc S., Giugliano, Robert P., Keech, Anthony C., Honarpour, Narimon, Wiviott, Stephen D., Murphy, Sabina A., Kuder, Julia F., Wang, Huei, Liu, Thomas, Wasserman, Scott M., Sever, Peter S., Pedersen, Fish MP, Terje R., Abrahamsen, Te, Im, K, Kanevsky, E, Bonaca, Mp, Lira Pineda, A, Hanlon, K, Knusel, B, Somaratne, R, Kurtz, C, Scott, R, Accini Mendoza JL, Amerena, J, Badariene, J, Burgess, L, Ceska, R, Charng, Mj, Choi, D, Cobos, Jl, Dan, Ga, De Ferrari GM, Deedwania, Pc, Chopra, Vk, Erglis, A, Ezhov, Mv, Ferreira, J, Filipová, S, Gaciong, Za, Pasierski, T, Georgiev, Bg, Gonzalez-Galvez, G, Gouni-Berthold, I, Schäufele, T, Hirayama, A, Huber, K, Rammer, M, Kjaerulf Jensen, H, Wermuth, S, Jiang, L, Jukema, Jw, Kraydashenko, O, Leiter, La, Lewis, Bs, López-Miranda, J, Lorenzatti, Aj, Mach, F, Mcadam, B, Nilsson, L, Olsson, Å, Rallidis, L, Rogelio, Gg, Kerr Saraiva JF, Scheen, A, Schiele, F, Scott, Rs, Connolly, D, Siu, Cw, Tay, L, Thorgeirsson, G, Tikkanen, Mj, Tokgozoglu, Sl, 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Tahirkheli, N, Delgado, E, Derian, W, Greenwald, J, Harris, M, Jackson, R, Marhefka, G, Mcelveen, W, Mooss, A, Morris, P, Murray, J, Pearlstein, P, Raisinghani, A, Rezkalla, S, Sakhrani, L, Schreibman, D, Shaoulian, E, Steinsapir, J, Yataco, A, De La Cruz, A, Fredrick, M, Goldenberg, E, Lee, D, Mccullum, K, Mclellan, B, Stephens, L, Wilson, S, Alfieri, A, Mandviwala, M, Orourke, D, Samal, A, Schmedtje, J, Waxman, F, Carhart, R, Clements, B, Dyke, C, Ghali, J, Gruberg, L, Hack, T, Jehle, A, Pogue, B, Schooley, C, and Shifrin, G

Subjects
Male, STATIN THERAPY, 2700 General Medicine, Disease, Cardiovascular, PLACEBO-CONTROLLED TRIAL, Gastroenterology, 0302 clinical medicine, Anticholesteremic Agent, Medicine, Myocardial infarction, 11 Medical and Health Sciences, ddc:616, Incidence, Antibodies, Monoclonal, General Medicine, Cholesterol, Cardiovascular Diseases, Monoclonal, Drug Therapy, Combination, Proprotein Convertase 9, Antibody, Aged, Anticholesteremic Agents, Atherosclerosis, Cholesterol, LDL, Double-Blind Method, Female, Follow-Up Studies, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypercholesterolemia, Least-Squares Analysis, Middle Aged, Medicine (all), REDUCING LIPIDS, Human, medicine.medical_specialty, Evinacumab, Clinical Trials and Supportive Activities, PCSK9 INHIBITION, Follow-Up Studie, LDL, 03 medical and health sciences, Drug Therapy, Clinical Research, LDL-C, Least-Squares Analysi, Science & Technology, Unstable angina, PCSK9, medicine.disease, chemistry, Clinical Biochemistry, 030204 cardiovascular system & hematology, Bococizumab, FOURIER Steering Committee and Investigators, Medical and Health Sciences, chemistry.chemical_compound, Antibodies monoclonal, Cardiovascular Disease, 030212 general & internal medicine, Stroke, Humanized, RISK, biology, PCSK9 Inhibitors, 10051 Rheumatology Clinic and Institute of Physical Medicine, Heart Disease, Atherosclerosi, 6.1 Pharmaceuticals, Combination, Cardiology, Life Sciences & Biomedicine, Antibodies, Monoclonal, Humanized, EZETIMIBE, 610 Medicine & health, Antibodies, Medicine, General & Internal, General & Internal Medicine, Internal medicine, CORONARY-HEART-DISEASE, In patient, Heart Disease - Coronary Heart Disease, Alirocumab, Ldl cholesterol, business.industry, Evaluation of treatments and therapeutic interventions, Evolocumab, Good Health and Well Being, Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, biology.protein, MODERATE, Hydroxymethylglutaryl-CoA Reductase Inhibitor, business
Abstract

Background Evolocumab is a monoclonal antibody that inhibits proprotein convertase subtilisin–kexin type 9 (PCSK9) and lowers low-density lipoprotein (LDL) cholesterol levels by approximately 60%. Whether it prevents cardiovascular events is uncertain. Methods We conducted a randomized, double-blind, placebo-controlled trial involving 27,564 patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or higher who were receiving statin therapy. Patients were randomly assigned to receive evolocumab (either 140 mg every 2 weeks or 420 mg monthly) or matching placebo as subcutaneous injections. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The median duration of follow-up was 2.2 years. Results At 48 weeks, the least-squares mean percentage reduction in LDL cholesterol levels with evolocumab, as compared with placebo, was 59%, from a median baseline value of 92 mg per deciliter (2.4 mmol per liter) to 30 mg per deciliter (0.78 mmol per liter) (P

Published
2017

35. Signatures of volatiles in the lunar proton albedo

Author

A., Schwadron N., K., Wilson J., D., Looper M., P., Jordan A., E., Spence H., B., Blake J., W., Case A., C., Kasper J., M., Farrell W., J., Lawrence D., Lovadiotis, G., Mazur, J., Petro, N., Pieters, C., S., Robinson M., Smith, S., and W., Townsend L.

Subjects
Astrophysics::High Energy Astrophysical Phenomena, Physics::Space Physics, Astrophysics::Instrumentation and Methods for Astrophysics, Astrophysics::Earth and Planetary Astrophysics, Nuclear Experiment
Abstract

We find evidence for hydrated material in the lunar regolith using “albedo protons” measured with the Cosmic Ray Telescope for the Effects of Radiation (CRaTER) on the Lunar Reconnaissance Orbiter (LRO). Fluxes of these albedo protons, which are emitted from the regolith due to steady bombardment by high energy radiation (Galactic Cosmic Rays), are observed to peak near the poles, and are inconsistent with the latitude trends of heavy element enrichment (e.g., enhanced Fe abundance). The latitudinal distribution of albedo protons anti-correlates with that of epithermal or high energy neutrons. The high latitude enhancement may be due to the conversion of upward directed secondary neutrons from the lunar regolith into tertiary protons due to neutron–proton collisions in hydrated regolith that is more prevalent near the poles. The CRaTER instrument may thus provide important measurements of volatile distributions within regolith at the Moon and potentially, with similar sensors and observations, at other bodies within the Solar System.

Published
2016

36. Solar modulation of the deep space galactic cosmic ray lineal energy spectrum measured by CRaTER, 2009-2014

Author

W., Case A., A., Schwadron N., E., Spence H., E., Mazur J., J., Joyce C., D., Looper M., Jordan, A., R., Rios R., W., Townsend L., C., Kasper J., B., Blake J., Smith, S., and Wilson, J.

Subjects
Astrophysics::High Energy Astrophysical Phenomena, Physics::Space Physics, Astrophysics::Solar and Stellar Astrophysics, Astrophysics::Earth and Planetary Astrophysics
Abstract

The Cosmic Ray Telescope for the Effects of Radiation (CRaTER) is an energetic particle detector flying aboard the Lunar Reconnaissance Orbiter. Since arriving at the Moon in 2009, CRaTER has observed the deep solar minimum of solar cycle 23, the ascending phase of cycle 24, the very weak maximum of cycle 24, and in recent months, what appears to be the start of the descending phase of cycle 24. In earlier work, we presented lineal energy spectra of galactic cosmic rays (GCRs) at solar minimum for different shielding depths. The long period of CRaTER observations allows us to study the evolution of these spectra as a function of solar modulation. As solar modulation increases, the total flux of GCRs decreases, and lower-energy ions are preferentially removed from the spectrum of ions that arrive in the inner heliosphere. These effects lead to modest variations in the lineal energy spectrum as a function of time. GCR fluxes at the 2009/2010 solar minimum were high by historical standards and at solar maximum remained high compared to earlier maxima.

Published
2016

40. In Situ Data and Effect Correlation During September 2017 Solar Particle Event

Author

Jiggens, P., primary, Clavie, C., additional, Evans, H., additional, O'Brien, T. P., additional, Witasse, O., additional, Mishev, A. L., additional, Nieminen, P., additional, Daly, E., additional, Kalegaev, V., additional, Vlasova, N., additional, Borisov, S., additional, Benck, S., additional, Poivey, C., additional, Cyamukungu, M., additional, Mazur, J., additional, Heynderickx, D., additional, Sandberg, I., additional, Berger, T., additional, Usoskin, I. G., additional, Paassilta, M., additional, Vainio, R., additional, Straube, U., additional, Müller, D., additional, Sánchez‐Cano, B., additional, Hassler, D., additional, Praks, J., additional, Niemelä, P., additional, Leppinen, H., additional, Punkkinen, A., additional, Aminalragia‐Giamini, S., additional, and Nagatsuma, T., additional

Published
2019
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42. Impact of Spontaneous Extracranial Bleeding Events on Health State Utility in Patients with Atrial Fibrillation: Results from the ENGAGE AF‐TIMI 48 Trial

Author

Senior, R., Paul, J., McKnight, T., Formoso, I., Saravia Toledo, S., Codutti, O., Sanjurjo, M., Bowen, L., Sanchez, A., Alvarez, M., Rodriguez, M., Navarrete, S., Ramos, H., Venturini, C., Prado, A., Fernandez, E., Pozzer, D., Casares, E., Povedano, G., Tommasi, A., Piskorz, D., Verdini, E., Nul, D., Gandur, H., Muntaner, J., Funes, I., Marino, J., Calderon, M., Manuale, O., Carne, M., Mackinnon, I., Raimondi, G., Lotti, J., Shatsky, K., Rodkey, K., Lorente, C., Vignau, S., Llanos, J., Nigro, A., Litvak, B., Iglesias, M., Liniado, G., Belcuore, M., Lanternier, G., Monaco, F., Kevorkian, R., Jure, D., Jure, H., Bianchini, M., Avery, D., Hominal, M., von Wulffen, M., McKenzie, M., Miranda, J., Wright, L., Pye, M., Flint, L., Newby, D., Andrews, A., Goicoechea, R., Huerta, M., Giannaula, R., Eden, M., Giacomi, G., Ceirano, C., Garrido, M., Perlo, D., Garcia Duran, R., Meiller, F., Gant Lopez, J., Zanotti, A., Fuselli, J., Arrieta, M., Femenia, F., Falu, E., Facello, M., Facello, A., Murdoch, D., Helliwell, L., More, R., Isted, C., Maxwell, T., Jones, D., Marazzi, P., McGhee, C., MacLeod, M., Ebano, P., MacCallum, P., Davolos, M., Estol, C., Moreno, V., Dran, R., Cendali, G., D'Amico, A., Bocanera, M., Cuneo, C., Rosell, M., Cuello, J., Morandini, M., Colombo, H., Brown, R., Saa Zarandon, R., Caruso, O., Novas, V., Cartasegna, L., Fracaro, V., Caccavo, A., Saravia, M., Bustamante Labarta, G., Valle, M., Budassi, N., Lip, G., Finlayson, M., Linker, N., McGuire, K., Atkinson, C., Lindsay, S., Ramasamy, V., Lie, F., Dickinson, D., Douglas, H., D'Costa, D., Wilmott, R., Cohen, A., Duff, J., Choy, A., Davies, D., Chapman, O., Dougal, K., Camm, J., Price, R., Blagden, M., Schwarz, L., McGarvey, J., Stubbs, L., McCartney, M., Hicks, T., Massin, E., Bedenko, E., Marenberg, M., Rabadi-Marar, D., Dunn, S., Beeton, I., Smith, S., Aggarwal, R., Marar, I., Hernandez, S., Berli, M., Petrucci, J., Beloscar, J., Caceres, M., Amuchastegui, M., Ameriso, P., Ameriso, S., Garcia, M., Alvarez, C., Reguero, M., Allall, O., Rosales, E., Albisu, J., Ahuad Guerrero, R., Gonzalez, C., Vogelmann, O., Magnuson, Elizabeth A., Cohen, David J., Giugliano, Robert P., Mandviwala, M., Casas, R., Makam, S., Lisiecki, B., Mainigi, S., Doctor, A., Magee, A., Bush, D., Macomber, J., Edelstein, J., Lurie, M., Wright, H., Lui, H., Ault, S., Looby, R., Davids, M., Lone, B., Shah, D., Lomnitz, D., Wofford, E., Littlefield, R., Murphy, R., Ling, L., Miller, D., Lillestol, M., Bonds, C., Lewis, D., Hartley, L., Lesser, M., Smith, D., Lentz, M., Royse, H., Ledbetter, L., Faucett, S., Langevin, E., Simmons, T., Lang, J., Ferguson, D., Landau, C., Coyle, G. Stagi, Lambert, C., Jauregui, V., Laliotis, A., Marquez, D., Krichmar, P., Watts, S., Kozlowski, J., Sanchez, E., Kotha, P., Godfrey, C., Korpas, D., Averett, P., Kindman, L., Khan, G., Khan, M., Binns, M., Khan, B., DiCorcia, L., Kesselbrenner, M., Buhler, A., Kersh, R., Bartholomaus, D., Kerkering, M., Keller, J., Keller, R., Davis, C., Kastelic, R., Behm, K., Karunaratne, H., Ruggiero, M., Kapoor, A., Cook, S., Kaplan, K., Kostedt, G., Kandath, D., Dugal, J., Kai, W., Coombs, V., Kahn, B., Royes, A., Judson, P., Nichols, M., Jovin, I., Hughett, G., Jones, R., Phillips, T., Johnson, F., Andresen, T., Jardula, M., Butcher, S., Ison, R., Tambawala, M., Hussain, M., Garza, M., Hurst, P., Battistelli, E., Hunter, J., Truva, C., Huang, P., Craft, D., Howard, L., Hays, D., Howard, V., Adams, K., Houchin, V., Turner, N., Hotchkiss, D., Sloss, D., Horton, K., Homayouni, A., Homan, J., Young, C., Hoekstra, J., Dutter, S., Hippert, R., Vieira, P., Hinchman, D., Carey, G., Herson, S., Miranda, D., Herrod, J., Batchell, K., Hermany, P., Harkins, V., Henry, S., Millard, D., Henderson, D., Dandekar, U., Heiman, M., Krater, C., Hearne, S., Bobade, M., Harris, J., Cavanna, L., Han, M., Bentivenga, L., Hamroff, G., Morelli, L., Hack, T., McLean, R., Gvora, T., Felsman, D., Guthrie, R., Foster, B., Guerrero, Guerrero, Fisher, M., Guarnieri, T., Gabela, W., Guarino, J., Mabe, K., Grove, D., Davis, A., Grossman, C., Goodman, V., Griffin, J., Aull, L., Griffin, S., Bonora, M., Graham, S., Rafala, E., Gowda, S., Goldstein, M., Latteri, J., Goldscher, D., Ewing, B., Gogia, H., Keane-Richmond, P., Gillespie, E., Hinchion, N., Gerber, J., Valentine, H., George, F., Garb, J., Jones, J., Gaffney, M., Smith, K., Friedlander, I., Morales, C., French, W., Gentry, P., Franco, M., Thrope, C., Frais, M., Solis, A., Forman, S., Slayton, C., Flores, E., Donahue, S., Fishbein, G., Drew, B., Fischell, T., Lim, G., Finkelstein, S., Shriver, D., Finkel, M., Calvo, M., Fialkow, J., Prior, J., Felten, W., Tang, N., Feldman, J., Tameron, A., Feld, L., Watkins, D., Fahmy, R., DeSalle, D., Everhart, B., Shipp, A., Ettinger, N., O'Brien, J., Johnson, C., Erenrich, N., Cristaldi, J., Ellis, J., Quick, R., Eldadah, Z., Dunn, K., Eade, J., Cullen, T., D'Souza, A., Habibi, S., Drozdiak, R., Olson, A., Dotani, I., Rodriguez, L., Donovan, D., Tisdale, L., DiGiovanna, M., Ucik, S., Dhar, S., Briscoe, C., Devenport, S., Waters, L., Desire, A., Steward, A., Desai, A., Carey, J., DeGarmo, R., Warmack, D., Dean, J., Debes, C., De Lemos, J., Ebreo, N., Davuluri, A., Dave, B., Dave, K., Wulf, A., Datta, S., Leka, G., Daniels, S., Morgan, T., Dang, N., Sarpola, N., Curtis, B., Nelson, L., Cowan, L., Masson, E., Cottiero, R., Mullinax, K., Cossu, S., Svadbik, L., Corbett, B., Martinez, E., Concha, M., Cole, J., Salpas, S., Colan, D., Bossaers, J., Cohen, R., Dutka, C., McClelland, M., Clay, A., Clapp, T., Bagby, J., Ciaramita, J., Sawaya, K., Chaturvedi, S., Tamayo, M., Charlat, M., Hatfield, G., Chang, M., Phan, D., Carr, K., Jameson, L., Caplan, J., Hartranft, E., Canosa, R., Canaday, D., Morton, S., Cader, C., Al-Maliky, T., Bybee, K., Triano, A., Brown, H., Frey, W., Brilakis, E., Terry, P., Bradley, A., Ziegler, K., Bowden, W., Wade, W., Bouchard, A., Hickenbotham, D., Borsheim, M., Vernon, M., Blue, B., Bloomberg, K., Bloomberg, R., Ensminger, E., Blonder, R., Talbot-Lawson, C., Block, T., Antonino, M., Bingham, S., Langone, L., Bilazarian, S., Preston, S., Bilal, B., Eldred, R., Bernard, J., Ibarra, M., Berk, M., Garman, V., Bensimhon, D., Swaim, D., Beinart, S., Craig, M., Bedwell, N., Luis-Valdes, M., Bedoya, R., Hoffman, T., Beasley, R., Benton, J., Bartkowiak, A., Gordon, L., Barrington, P., Faircloth, C., Barker, T., Altonen, D., Barber, M., Campbell, G., Baman, R., Batista, M., Baine, S., Thompson, B., Ayesu, K., Baldwin, E., Awasty, V., Cobos, D., Aude, Y., Strickland, S., Attanti, S., Rasmussen, L., Arouni, A., Shoaf, R., Arnold, T., York, T., Anderson, J., Persechino, F., Amin, M., Khetarpal, S., Amin, K., Lane, B., Alsheikh, T., MacDonald, H., Almquist, A., Biscardi, R., Allison, J., Godsey, W., Aliyar, P., Genova-Peeva, E., Alexander, J., Brubaker, S., Akhter, F., Ahmadpour, H., Hussain, A., Ahmad, A., Beck, P., Reiling, S., Adler, P., Barash, B., Adler, J., Lohman, J., Panella, M., Abi-Mansour, P., Roberts, J., Mackin, A., Moriarty, A., Green, M., Shandra, T., Zhurba, S., Logvinov, Y., Zharinov, O., Mudruk, I., Yena, L., Nahrebetskyy, V., Yagensky, A., Serik, S., Volkov, V., Goncharov, O., Vizir, V., Sklyanna, O., Vatutin, M., Drapchak, I., Vakaliuk, I., Tykhonova, S., Kuznetsov, I., Tseluyko, V., Lyzohub, S., Sychov, O., Perebetiuk, L., Stanislavchuk, M., Sirenko, Y., Zamlynskyy, M., Shvetz, N., Goncharova, I., Shcherbak, V., Ishchuk, V., Shatilo, V., Rudyk, I., Chendey, T., Rishko, M., Gamachek, O., Rebrov, B., Leonidova, V., Prokhorov, O., Nekrasa, A., Potapenko, P., Dovgan, N., Parkhomenko, A., Ushakova-Sokolova, L., Ostrovska, L., Fedotov, S., Malynovsky, Y., Gorna, O., Lizogub, V., Kyyak, Y., Kupnovytska, I., Stets, R., Kraydashenko, O., Usan, N., Kraiz, I., Kaplan, P., Koval', O., Ohirko, O., Koval, V., Dvoieglazova, M., Kotseruba, V., Petyunina, O., Kopytsya, M., Vasylets, V., Kolomyyits, S., Gerasimenko, N., Kaydashev, I., Blihar, O., Karpenko, Y., Nevolina, I., Karpenko, O., Samburg, Y., Godlevska, O., Husyev, V., Horbach, L., Dzublik, Y., Gavrysyuk, V., Sorokivskyy, M., Faynyk, A., Vasilyeva, L., Dzyak, G., Kulynych, R., Dotsenko, S., Lebedynskaya, M., Bereznyakov, I., Vlasyuk, Z., Bazylevych, A., Azhdari, M., Batushkin, V., Zoghi, M., Yigit, Z., Yigit, F., Tandogan, I., Turgut, O., Oto, A., Kanadasi, M., Kabul, K., Ermis, C., Erdogan, D., Ceyhan, C., Cayli, M., Calik, A., Cakmak, N., Bayata, S., Ata, N., Demir, H., Akilli, H., Acikel, M., Puripun, E., Vorasettakarnkij, Y., Mekara, W., Sukonthasarn, A., Panpunuan, P., Sritara, P., Sripracha, A., Piyayotai, D., Bamrungpong, P., Laothavorn, P., Sriprasert, S., Kiatchoosakun, S., Sinthusopa, W., Kaewsuwanna, P., Pornchaiyasit, K., Jirasirirojanakorn, K., Kuo, J. Y., Yeh, H. I., Tsai, W. C., Lee, S. C., Ueng, K. C., Pan, Y. F., Tseng, W. K., Chiu, C. Z., Shyu, K. G., Lin, K. H., Pai, P. Y., Lee, J. T., Lin, T. H., Lai, W. T., Wang, C. L., Kuo, C. T., Chen, Y. F., Huang, J. L., Chen, Y. P., Hsia, C. H., Yeh, T. C., Chiou, C. W., Wu, Y. W., Chiang, F. T., Yu, W. C., Chiang, C. E., Wu, W. S., Cheng, C. C., Slater, I. Petrova, Moccetti, T., Broberg, M., Thulin, J., Gunnarsson, A., Stenberg, A., Sundholm, C., Ronn, F., Johansson, M., Rautio, A., Moodh, J., Randers, F., Eriksson, G., Malmqvist, L., Edlund, M., Kozak, P., Hakansson, E., Koskinen, P., Jernhed, H., Juul-Moller, S., Winberg, L., Herlitz, J., Karlsson, L., Engdahl, J., Ostberg, S., Dettmann, S., Bengtsson, A. Stener, Carlsson, T., Persson, L., Blomstrom, P., Andersson, R., Blom, K. Berndtsson, Akerberg, A., Appelros, P., Astier, L., Villuendas, R., Dachs Delgado, M., Terns, M., Fernandez Alvarez, R., Fernandez, M., Arias, J., Diaz-Pintado, M., Merino, J., Blanco Abril, S., Manzano, L., Barquero, R., Lopez Garcia-Aranda, V., Delgado, A., Hernandez Madrid, A., Moure, M., Gonzalez Juanatey, J., Perez Guevara, M., Diez Tejedor, E., Asensio, A., De Arce Borda, A., Calvo, G., Calvo, C., Cabero, P., Bruguera Cortada, J., Puertas, I., Blanco Coronado, J., Manzanal Rey, A., Arcocha Torres, M., Kim, J. Y., Rim, S. J., Na, J. O., Rha, S. W., Kwak, J. J., Namgung, J., Shin, D. G., Lee, S. H., Joung, B. Y., Lee, M. H., Chun, M. Y., Kim, Y. J., Seo, J. B., Kim, S. H., Park, S. J., Kim, J. S., Park, J. H., Kim, J. H., Park, M. S., Kim, J. T., Cha, M. J., Kim, H. S., Seo, J. S., Kim, D. S., Jin, E. S., Kim, C. J., Choi, K. J., Kang, D. H., Lee, J. M., Jeon, H. K., Jung, J. W., Hyon, M. S., Lee, H. W., Hong, T. J., Lee, K. H., Han, S. H., Oh, Y. S., Chung, W. S., Hong, K. 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J., Romero-Colon, J., Michlin, B., Slaby, J., Reichert, P., Jirsova, E., Podrazil, P., Pisova, J., Havlova, I., Petrova, I., Peterka, K., Olsr, J., Nechanicky, R., Melichar, M., Krocova, E., Machova, V., Ludka, O., Cajulis, C., Kvasnicka, J., Kuchar, R., Kovar, P., Kosek, Z., Kostkova, G., Kochrt, M., Kobza, R., Jirmar, R., Jerabek, O., Jelinek, Z., Jarkovsky, P., Jandik, J., Hubac, J., Honkova, M., Gregor, P., Golan, L., Francek, L., Florian, J., Ferkl, R., Elbl, L., Cermak, O., Burianova, H., Brtko, M., Kunkelova, V., Berka, L., Brodova, P., Bar, M., Bergovec, M., Vrazic, H., Bakliza, Z., Sutalo, K., Kirner, D., Steiner, R., Cvitkusic Lukenda, K., Samardzic, P., Buksa, B., Knezevic, A., Jaksic Jurinjak, S., Jelic, V., Makar Ausperger, K., Francetic, I., Romic, I., Ferri Certic, J., Tusek, S., Ciglenecki, N., Jeric, M., Car, S., Carevic, V., Bagatin, J., Perdomo Mejia, I., Sanchez Vallejo, G., Gonzales, C., Quintero, A., Fonseca, J., Orozco Linares, L., Lopez Giraldo, D., Moncada Corredor, M., Rivera Rodriguez, E., Manzur, F., Builes, A., Jaramillo Munoz, C., Delgado, P., Hernandez, H., Aldana Diaz, I., Fernandez Ruiz, R., Arroyave, C., Delgado Restrepo, J., Leon Pineda, L., Cano, N., Accini, M., Accini, J., Zhang, Y. L., Zhou, S. X., Li, B. G., Zheng, Z. Q., Wang, J. Q., Zhao, X. L., Han, R. J., Zhao, R. P., Kang, H., Zhang, Z., Lin, Y. N., Zhang, H. Q., Qiang, H., Yuan, Z. Y., Li, L. L., Yu, B., Xu, Y. P., Yin, Y. H., Gao, M., Zheng, Y., Zheng, X., Yang, Y. J., Li, A. Y., Yang, K., Liang, Y. Z., Xu, Y. M., Gu, J. Y., Xu, J. H., Li, Y. E., Wu, S. L., Huang, D., Wei, M., Shi, X. J., Wang, G. P., Qi, S. Y., Wang, D. M., Yang, Z. Y., Ma, S. M., Lu, Z. H., Liu, L., Gu, X. J., Liao, D. N., Liu, Y., Li, Z. Q., Liu, B., Li, W. M., Kong, Y. Q., Li, T. F., Liu, H., Li, L., Qu, Z., Jiang, X. J., Qiu, Y., Hong, L., You, Z. G., Hong, K., Zhang, P., Fu, G. S., Feng, C., Dong, Y. G., Zhang, X., Chen, X. P., Xie, X. D., Chen, J. Z., Xu, G. L., Bai, F., Grandon Azua, M., Yovaniniz, P., Lara Lara, C., Stockins, B., Campisto, Y., Zapata Staub, J., Potthoff, S., Torres Carrasco, G., Pincetti, C., Carmona Perez, M., Opazo, M., Romero Llamas, R., Martinez, D., Manriquez Silva, L., Manriquez, L., Rebolledo, C., Lopetegui, M., Arratia Diaz, P., Florenzano, F., Parada, A., Corbalan, R., Obreque, C., Cobos, J., Mondaca Mondaca, P., Bugueno, C., Retamal Matus, L., Balboa, W., Mabee, J., Woodford, T., Caterini, T., Wharton, S., Morley, A., Wahby, R., Giesbrecht, L., Velthuysen, G., Teitelbaum, J., Teitelbaum, I., Tremblay, M., Talbot, P., David, D., Talajic, M., Bobbie, C., Syan, G., Kailey, P., Sussman, J., St-Hilaire, R., Silverio, G., Shu, D., Marchand, C., Rupka, D., Bozek, B., Ricci, J., Nethercott, C., Qureshi, A., Mercado, A., Cervellione, K., Mendelson, R., Turri, L., Polasek, P., Sardin, V., Pesant, Y., Carroll, L., Parkash, R., Bolton, R., O'Mahony, W., Banville, P., O'Hara, G., Nicholson, R., Lamoureux, U., Najarali, A., Krider, J., Mucha, M., Roth, M., Morrison, D., Morely, A., Mawji, A., Studenikow, E., Maranda, C., Vaillancourt, T., Malette, P., Matthews, J., MacCallum, C., Seib, M., Ma, P., Douglas, S., Luton, R., Roberts, P., Lichtenstein, T., Lam, H., Lam, S., St-Germain, L., Lainesse, A., Dewar, C., Labonte, R., Roy, M., Kouz, S., Perkins, L., Huynh, T., Standring, R., Hoag, G., Ho, V., Ho, K., Scott, L., Heath, J., Hatheway, R., Houbraken, D., Viau, C., Fortin, C., Zondag, M., Eikelboom, J., Dufresne, M., Kubanska, A., du Preez, M., Denis, I., Coutu, B., Masson, C., Costi, P., Gauthier, M., Constance, C., Valley, S., Cleveland, D., Vansickle, L., Chilvers, M., Lepage, C., Chehayeb, R., Otis, J., Cha, J., Hundseth, M., Bose, S., Stafford, C., Bhargava, R., Antle, S., Archibald, J., Manoylov, E., Kitova, M., Tzekova, M., Tumbeva, D., Tumbev, H., Nyagina, M., Todorov, G., Momchilova-Lozeva, D., Staneva, A., Vasilev, I., Popov, A., Milusheva, T., Petranov, S., Kostov, K., Pencheva, G., Vasilev, D., Nikolov, F., Stoyanovski, V., Mincheva, V., Miteva, B., Mihov, A., Manolova, A., Kamenova, P., Hergeldjieva, V., Kinova, E., Goudev, A., Kostova, E., Georgiev, B., Wall, J., Gergova, V., Donova, T., Milcheva, N., Denchev, S., Parishev, G., Chompalova, B., Zimmermann, E. Burger, Zimmermann, S., Almeida, M., Boas, F. Villas, Lustosa, E., Sobral Filho, D., Carraro, A., Simoes, M., Vicente, C., Saraiva, J., do Val, R., Sampaio, R., Pagnan, L. Goncalves, dos Santos, F. Rossi, Rodrigues, D., Rodrigues, A., Rocha, M. Rubia, Rodrigues, L., Barros, R., Rocha, J., Leipelt, J., Katz Weiand, L. Reis, Avellar, K., Reis, G., Gozalo, A., Almeida, J. Pimenta, Luiz, R. Osorio, Leaes, P., Morales, K., Sebba Barroso de Souza, W. Kunz, Radaelli, G., Kalil, C., Almeida, A., Kaiser, S., Cury, C., Jorge, J., Pereira, L., Jaeger, C., Ninho, L., Guimaraes, A., Gomes, A., Gomes, M., Pereira, G., Gagliardi, R., Daitz, C., Finimundi, H., Araujo, E., Ferreira, L., Seroqui, M., Saporito, W. Faustino, Morgado, S., Dutra, O., Laimer, R., Duda, N., Pereira, V., De Patta, M., Barroso, D., Costantini, C., Silva, J., Chaves Junior, H., Fleck, N., Brondani, R., Cunha, S., Botelho, R., Sehnem, E., Precoma, D. Bertolim, Ferraz, R. Franchin, Alves da Costa, F. Augusto, Motta, C., Atie, J., de Melo, R. Ferreira, Lotufo, P. Andrade, Coutinho, E., Vincenzo de Paola, A. Amato, Denie, D., Wollaert, B., Beerts, C., Vrolix, M., Mestdagh, I., Vervoort, G., van Welden, J., Vanwelden, J., Derycker, K., Vandekerckhove, Y., Jacobs, C., Mehrle, A., Skinner, J., Meholick, A., Marti, J., Mega, J., Lack, A., Stockman, D., Huyberechts, D., Scavee, C., Clinckemaille, N., Parque, J., Raepers, M., Mairesse, G., Malmendier, D., Herzet, J., Meeusen, K., Heidbuchel, H., Tincani, G., Desfontaines, P., De Bruyne, L., De Tollenaere, M., de Koning, K., De Bleecker, J., Banaeian, F., Capiau, L., O'Shea, V., Szto, G., Perrett, L., Purnell, P., Batta, C., Paul, V., Li, J., McKeirnan, M., Morrison, H., Wright, J., Wright, A., Chung, A., Watkin, R., Gilchrist, M., Venkataraman, A., Lehman, R., Jones, S., Gates, P., Flecknoe-Brown, S., Silver, G., Davis, S., Kay, S., Dart, A., Slattery, A., Crimmins, D., Price-Smith, S., Colquhoun, D., Hoffmann, B., Arstall, M., Paraskevaidis, T., Anderson, C., Morell, Y., Vico, M., Teves, M., Sosa Liprandi, M., Morara, P., Severino, P., Buzzetti, C., Schygiel, P., Walker, M., Turner, W., Bridge, C., Storey, R., Goloboulicz, A., Schmidberg, J., Kennard, S., Sopher, M., McLaurin, B., Young, G., Kwong, Winghan J., Antman, Elliott M., Ruff, Christian T., Wang, J. H., Iriarte, M., Morissette, A., Wang, Kaijun, Li, Haiyan, and Yalcin, R.

Subjects
Male, medicine.medical_specialty, Complications, Time Factors, Pyridines, Health Status, Embolism, Hemorrhage, Arrhythmias, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Risk Factors, Surveys and Questionnaires, Internal medicine, Atrial Fibrillation, Humans, Medicine, In patient, Prospective Studies, 030212 general & internal medicine, anticoagulation, Blood Coagulation, Original Research, Aged, Aged, 80 and over, Quality and Outcomes, business.industry, Anticoagulants, Atrial fibrillation, Middle Aged, bleeding, medicine.disease, Stroke, Thiazoles, Treatment Outcome, quality of life, utility, Physical therapy, Cardiology, Female, Warfarin, Gastrointestinal Hemorrhage, Cardiology and Cardiovascular Medicine, business, TIMI, Health Services and Outcomes Research, Factor Xa Inhibitors
Abstract

Background The impact of different types of extracranial bleeding events on health‐related quality of life and health‐state utility among patients with atrial fibrillation is not well understood. Methods and Results The ENGAGE AF ‐ TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48) Trial compared edoxaban with warfarin with respect to the prevention of stroke or systemic embolism in atrial fibrillation. Data from the EuroQol‐5D ( EQ ‐5D‐3L) questionnaire, prospectively collected at 3‐month intervals for up to 48 months, were used to estimate the impact of different categories of bleeding events on health‐state utility over 12 months following the event. Longitudinal mixed‐effect models revealed that major gastrointestinal bleeds and major nongastrointestinal bleeds were associated with significant immediate decreases in utility scores (−0.029 [−0.044 to −0.014; P P =0.001], respectively). These effects decreased in magnitude over time, and were no longer significant for major nongastrointestinal bleeds at 9 months, but remained borderline significant for major gastrointestinal bleeds at 12 months. Clinically relevant nonmajor and minor bleeds were associated with smaller but measurable immediate impacts on utility (−0.010 [−0.016 to −0.005] and −0.016 [−0.024 to −0.008]; P Conclusions All categories of bleeding events were associated with negative impacts on health‐state utility in patients with atrial fibrillation. Major bleeds were associated with relatively large immediate decreases in utility scores that gradually diminished over 12 months; clinically relevant nonmajor and minor bleeds were associated with smaller immediate decreases in utility that persisted over 12 months. Clinical Trial Registration URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT00781391.

Published
2017

43. Towards a new proxy of continental atmospheric humidity: the triple oxygen isotopic composition of plant biosilica

Author

Alexandre, A., Pauchet, S, Landais, A, Piel, C, Devidal, S., Roy, J, Vallet-Coulomb, C, Sonzogni, C, Pasturel, M, Cornuault, P, Xin, J, Mazur, J. C., Prié, F, Bentaleb, I, Centre européen de recherche et d'enseignement des géosciences de l'environnement (CEREGE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Écotron Européen de Montpellier, Centre National de la Recherche Scientifique (CNRS), and Université de Montpellier (UM)

Subjects
[SDU.STU]Sciences of the Universe [physics]/Earth Sciences, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2016

44. Revising the self-report strengths and difficulties questionnaire for cross-country comparisons of adolescent mental health problems: the SDQ-R.

Author

Duinhof, E. L., Lek, K. M., de Looze, M. E., Cosma, A., Mazur, J., Gobina, I., Wüstner, A., Vollebergh, W. A. M., and Stevens, G. W. J. M.

Subjects
MENTAL health, CHILDREN with intellectual disabilities, ADOLESCENT health, HEALTH behavior, INVARIANT measures, PSYCHIATRIC research, TEENAGERS
Abstract

Aims: The Strengths and Difficulties Questionnaire (SDQ) has been used in many epidemiological studies to assess adolescent mental health problems, but cross-country comparisons of the self-report SDQ are scarce and so far failed to find a good-fitting, common, invariant measurement model across countries. The present study aims to evaluate and establish a version of the self-report SDQ that allows for a valid cross-country comparison of adolescent self-reported mental health problems. Methods: Using the Health Behaviour in School-aged Children study, the measurement model and measurement invariance of the 20 items of the self-report SDQ measuring adolescent mental health problems were evaluated. Nationally representative samples of 11-, 13- and 15-year old adolescents (n = 33 233) from seven countries of different regions in Europe (Bulgaria, Germany, Greece, the Netherlands, Poland, Romania, Slovenia) were used. Results: In order to establish a good-fitting and common measurement model, the five reverse worded items of the self-report SDQ had to be removed. Using this revised version of the self-report SDQ, the SDQ-R, partial measurement invariance was established, indicating that latent factor means assessing conduct problems, emotional symptoms, peer relationships problems and hyperactivity-inattention problems could be validly compared across the countries in this study. Results showed that adolescents in Greece scored relatively low on almost all problem subscales, whereas adolescents in Poland scored relatively high on almost all problem subscales. Adolescents in the Netherlands reported the most divergent profile of mental health problems with the lowest levels of conduct problems, low levels of emotional symptoms and peer relationship problems, but the highest levels of hyperactivity-inattention problems. Conclusions: With six factor loadings being non-invariant, partial measurement invariance was established, indicating that the 15-item SDQ-R could be used in our cross-country comparison of adolescent mental health problems. To move the field of internationally comparative research on adolescent mental health forward, studies should test the applicability of the SDQ-R in other countries in- and outside Europe, continue to develop the SDQ-R as a cross-country invariant measure of adolescent mental health, and examine explanations for the found country differences in adolescent mental health problems. [ABSTRACT FROM AUTHOR]

Published
2020
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47. Update on the Worsening Particle Radiation Environment Observed by CRaTER and Implications for Future Human Deep‐Space Exploration

Author

Schwadron, N. A., primary, Rahmanifard, F., additional, Wilson, J., additional, Jordan, A. P., additional, Spence, H. E., additional, Joyce, C. J., additional, Blake, J. B., additional, Case, A. W., additional, de Wet, W., additional, Farrell, W. M., additional, Kasper, J. C., additional, Looper, M. D., additional, Lugaz, N., additional, Mays, L., additional, Mazur, J. E., additional, Niehof, J., additional, Petro, N., additional, Smith, C. W., additional, Townsend, L. W., additional, Winslow, R., additional, and Zeitlin, C., additional

Published
2018
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48. Haplotype reference consortium panel: Practical implications of imputations with large reference panels

Author

Iglesias, A.I., Lee, S.J. van der, Bonnemaijer, P.W.M., Hohn, R., Nag, A., Gharahkhani, P., Khawaja, A.P., Broer, L., Foster, P.J., Hammond, C.J., Hysi, P.G., Leeuwen, E.M. van, MacGregor, S., Mackey, D.A., Mazur, J., Nickels, S., Uitterlinden, A.G., Klaver, C.C.W., Amin, N., Duijn, C.M. van, Iglesias, A.I., Lee, S.J. van der, Bonnemaijer, P.W.M., Hohn, R., Nag, A., Gharahkhani, P., Khawaja, A.P., Broer, L., Foster, P.J., Hammond, C.J., Hysi, P.G., Leeuwen, E.M. van, MacGregor, S., Mackey, D.A., Mazur, J., Nickels, S., Uitterlinden, A.G., Klaver, C.C.W., Amin, N., and Duijn, C.M. van

Abstract

Contains fulltext : 177754.pdf (Publisher’s version ) (Open Access), Recently, the Haplotype Reference Consortium (HRC) released a large imputation panel that allows more accurate imputation of genetic variants. In this study, we compared a set of directly assayed common and rare variants from an exome array to imputed genotypes, that is, 1000 genomes project (1000GP) and HRC. We showed that imputation using the HRC panel improved the concordance between assayed and imputed genotypes at common, and especially, low-frequency variants. Furthermore, we performed a genome-wide association meta-analysis of vertical cup-disc ratio, a highly heritable endophenotype of glaucoma, in four cohorts using 1000GP and HRC imputations. We compared the results of the meta-analysis using 1000GP to the meta-analysis results using HRC. Overall, we found that using HRC imputation significantly improved P values (P = 3.07 x 10-61 ), particularly for suggestive variants. Both meta-analyses were performed in the same sample size, yet we found eight genome-wide significant loci in the HRC-based meta-analysis versus seven genome-wide significant loci in the 1000GP-based meta-analysis. This study provides supporting evidence of the new avenues for gene discovery and fine mapping that the HRC imputation panel offers.

Published
2017

49. Haplotype reference consortium panel: Practical implications of imputations with large reference panels

Author

Iglesias González, A.I. (Adriana), Lee, S.J. (Sven) van der, Bonnemaijer, P.W. (Pieter W.M.), Höhn, R. (René), Nag, A. (Abhishek), Gharahkhani, P. (Puya), Khawaja, A.P. (Anthony P.), Broer, L. (Linda), Foster, P.J. (Paul J.), Hammond, C.J. (Christopher J.), Hysi, P.G. (Pirro), Leeuwen, E.M. (Elisa) van, Macgregor, S. (Stuart), Mackey, D.A. (David), Mazur, J. (Johanna), Nickels, S. (Stefan), Uitterlinden, A.G. (André), Klaver, C.C.W. (Caroline), Amin, N. (Najaf), Duijn, C.M. (Cornelia) van, Iglesias González, A.I. (Adriana), Lee, S.J. (Sven) van der, Bonnemaijer, P.W. (Pieter W.M.), Höhn, R. (René), Nag, A. (Abhishek), Gharahkhani, P. (Puya), Khawaja, A.P. (Anthony P.), Broer, L. (Linda), Foster, P.J. (Paul J.), Hammond, C.J. (Christopher J.), Hysi, P.G. (Pirro), Leeuwen, E.M. (Elisa) van, Macgregor, S. (Stuart), Mackey, D.A. (David), Mazur, J. (Johanna), Nickels, S. (Stefan), Uitterlinden, A.G. (André), Klaver, C.C.W. (Caroline), Amin, N. (Najaf), and Duijn, C.M. (Cornelia) van

Abstract

Recently, the Haplotype Reference Consortium (HRC) released a large imputation panel that allows more accurate imputation of genetic variants. In this study, we compared a set of directly assayed common and rare variants from an exome array to imputed genotypes, that is, 1000 genomes project (1000GP) and HRC. We showed that imputation using the HRC panel improved the concordance between assayed and imputed genotypes at common, and especially, low-frequency variants. Furthermore, we performed a genome-wide association meta-analysis of vertical cup-disc ratio, a highly heritable endophenotype of glaucoma, in four cohorts using 1000GP and HRC imputations. We compared the results of the meta-analysis using 1000GP to the meta-analysis results using HRC. Overall, we found that using HRC imputation significantly improved P values (P = 3.07 × 10-61), particularly for suggestive variants. Both meta-analyses were performed in the same sample size, yet we found eight genome-wide significant loci in the HRC-based meta-analysis versus seven genome-wide significant loci in the 1000GP-based meta-analysis. This study provides supporting evidence of the new avenues for gene discovery and fine mapping that the HRC imputation panel offers.

Published
2017
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50. Comparison of HapMap and 1000 genomes reference panels in a large-scale genome-wide association study

Author

Vries, P.S. (Paul) de, Sabater-Lleal, M. (Maria), Chasman, D.I. (Daniel), Trompet, S. (Stella), Ahluwalia, T.S. (Tarunveer Singh), Teumer, A. (Alexander), Kleber, M.E. (Marcus), Chen, M.-H. (Ming-Huei), Wang, J.J. (Jie Jin), Attia, J. (John), Marioni, R.E. (Riccardo), Steri, M. (Maristella), Weng, L.-C. (Lu-Chen), Pool, R. (Reńe), Grossmann, V. (Vera), Brody, J.A. (Jennifer A.), Venturini, C. (Cristina), Tanaka, T. (Toshiko), Rose, L.M. (Lynda), Oldmeadow, C. (Christopher), Mazur, J. (Johanna), Basu, S. (Saonli), Frånberg, M. (Mattias), Yang, Q. (Qiong), Ligthart, S. (Symen), Hottenga, J.J. (Jouke Jan), Rumley, A. (Ann), Mulas, A. (Antonella), Craen, A.J. (Anton) de, Grotevendt, A. (Anne), Taylor, K.D. (Kent D.), Delgado, G., Kifley, A. (Annette), Lopez, L.M. (Lorna), Berentzen, T.L. (Tina L.), Mangino, M. (Massimo), Bandinelli, S. (Stefania), Morrison, A.C. (Alanna C.), Hamsten, A. (Anders), Tofler, G.H. (Geoffrey), Maat, M.P.M. (Moniek) de, Draisma, G. (Gerrit), Lowe, G.D. (Gordon D.), Zoledziewska, M. (Magdalena), Sattar, N. (Naveed), Lackner, K.J. (Karl J.), Völker, U. (Uwe), McKnight, B. (Barbara), Huang, J. (Jian), Holliday, E.G. (Elizabeth), McEvoy, M.A. (Mark A.), Starr, J.M. (John), Hysi, P.G. (Pirro), Hernandez, D.G. (Dena), Guan, W. (Weihua), Rivadeneira Ramirez, F. (Fernando), McArdle, W.L. (Wendy), Slagboom, P.E. (Eline), Zeller, T. (Tanja), Psaty, B.M. (Bruce), Uitterlinden, A.G. (André), Geus, E.J.C. (Eco) de, Stott, D.J. (David J.), Binder, H. (Harald), Hofman, A. (Albert), Franco, O.H. (Oscar), Rotter, J.I. (Jerome I.), Ferrucci, L. (Luigi), Spector, T.D. (Tim D.), Deary, I.J. (Ian), März, W. (Winfried), Greinacher, A. (Andreas), Wild, P.S. (Philipp S.), Cucca, F. (Francesco), Boomsma, D.I. (Dorret), Watkins, H. (Hugh), Tang, W. (Weihong), Ridker, P.M. (Paul), Jukema, J.W., Scott, R.J. (Rodney J.), Mitchell, P. (Paul), Hansen, T. (T.), O'Donnell, C.J. (Christopher J.), Smith, N.L. (Nicholas L.), Strachan, D.P. (David P.), Dehghan, A. (Abbas), Vries, P.S. (Paul) de, Sabater-Lleal, M. (Maria), Chasman, D.I. (Daniel), Trompet, S. (Stella), Ahluwalia, T.S. (Tarunveer Singh), Teumer, A. (Alexander), Kleber, M.E. (Marcus), Chen, M.-H. (Ming-Huei), Wang, J.J. (Jie Jin), Attia, J. (John), Marioni, R.E. (Riccardo), Steri, M. (Maristella), Weng, L.-C. (Lu-Chen), Pool, R. (Reńe), Grossmann, V. (Vera), Brody, J.A. (Jennifer A.), Venturini, C. (Cristina), Tanaka, T. (Toshiko), Rose, L.M. (Lynda), Oldmeadow, C. (Christopher), Mazur, J. (Johanna), Basu, S. (Saonli), Frånberg, M. (Mattias), Yang, Q. (Qiong), Ligthart, S. (Symen), Hottenga, J.J. (Jouke Jan), Rumley, A. (Ann), Mulas, A. (Antonella), Craen, A.J. (Anton) de, Grotevendt, A. (Anne), Taylor, K.D. (Kent D.), Delgado, G., Kifley, A. (Annette), Lopez, L.M. (Lorna), Berentzen, T.L. (Tina L.), Mangino, M. (Massimo), Bandinelli, S. (Stefania), Morrison, A.C. (Alanna C.), Hamsten, A. (Anders), Tofler, G.H. (Geoffrey), Maat, M.P.M. (Moniek) de, Draisma, G. (Gerrit), Lowe, G.D. (Gordon D.), Zoledziewska, M. (Magdalena), Sattar, N. (Naveed), Lackner, K.J. (Karl J.), Völker, U. (Uwe), McKnight, B. (Barbara), Huang, J. (Jian), Holliday, E.G. (Elizabeth), McEvoy, M.A. (Mark A.), Starr, J.M. (John), Hysi, P.G. (Pirro), Hernandez, D.G. (Dena), Guan, W. (Weihua), Rivadeneira Ramirez, F. (Fernando), McArdle, W.L. (Wendy), Slagboom, P.E. (Eline), Zeller, T. (Tanja), Psaty, B.M. (Bruce), Uitterlinden, A.G. (André), Geus, E.J.C. (Eco) de, Stott, D.J. (David J.), Binder, H. (Harald), Hofman, A. (Albert), Franco, O.H. (Oscar), Rotter, J.I. (Jerome I.), Ferrucci, L. (Luigi), Spector, T.D. (Tim D.), Deary, I.J. (Ian), März, W. (Winfried), Greinacher, A. (Andreas), Wild, P.S. (Philipp S.), Cucca, F. (Francesco), Boomsma, D.I. (Dorret), Watkins, H. (Hugh), Tang, W. (Weihong), Ridker, P.M. (Paul), Jukema, J.W., Scott, R.J. (Rodney J.), Mitchell, P. (Paul), Hansen, T. (T.), O'Donnell, C.J. (Christopher J.), Smith, N.L. (Nicholas L.), Strachan, D.P. (David P.), and Dehghan, A. (Abbas)

Abstract

An increasing number of genome-wide association (GWA) studies are now using the higher resolution 1000 Genomes Project reference panel (1000G) for imputation, with the expectation that 1000G imputation will lead to the discovery of additional associated loci when compared to HapMap imputation. In order to assess the improvement of 1000G over HapMap imputation in identifying associated loci, we compared the results of GWA studies of circulating fibrinogen based on the two reference panels. Using both HapMap and 1000G imputation we performed a meta-analysis of 22 studies comprising the same 91,953 individuals. We identified six additional signals using 1000G imputation, while 29 loci were associated using both HapMap and 1000G imputation. One locus identified using HapMap imputation was not significant using 1000G imputation. The genome-wide significance threshold of 5×10-8 is based on the number of independent statistical tests using HapMap imputation, and 1000G imputation may lead to further independent tests that should be corrected for. When using a stricter Bonferroni correction for the 1000G GWA study (P-value < 2.5×10-8), the number of loci significant only using HapMap imputation increased to 4 while the number of loci significant only using 1000G decreased to 5. In conclusion, 1000G imputation enabled the identification of 20% more loci than HapMap imputation, although the advantage of 1000G imputation became less clear when a stricter Bonferroni correction was used. More generally, our results provide insights that are applicable to the implementation of other dense reference panels that are under development.

Published
2017
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