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13. Eficiencia productiva de la industria venezolana del hierro en la Región Guayana

Author

Jairo J. Pico F. and Hugo R. Martínez C.

Subjects
Political science (General), JA1-92, Social sciences (General), H1-99
Abstract

El objetivo general de la investigación fue analizar la eficiencia productiva de la industria venezolana de Hierro de Reducción Directa (HRD) en la Región Guayana en el periodo 2005 al 2009. La investigación fue explicativa. El método aplicadofue el hipotético deductivo con un diseño no experimental de corte transversal. La recolección de datos fue documental y la población fueron los reactores ubicados en la Región Guayana, ya que allí es donde se concentra toda la producción de HRD de Venezuela. La técnica de análisis de los datos aplicada fue Análisis Envolvente de Datos. Los resultados, indican que la producción de HRD está en descenso por la disminución de oferta de insumos (factores externos) y la ineficiencia del manejo de insumos (factores internos), siendo la más significativa los factores externos que representa un 74% de la producción y una perdida de 17.569 miles de toneladas, lo que significa un descenso de 1,02 miles de Toneladas anuales en los niveles de producción equivale una pérdida de 23.330 miles de toneladas en el lapso 2005-2009, un 38,7% de producción. Se concluye que es ineludible un cambio de actitud con criterio de competitividad en la conducción de la gestión de los procesos de producción de reducción directa de hierro

Published
2014

14. Discerning the Ambiguous Role of Missense TTN Variants in Inherited Arrhythmogenic Syndromes

Author

Martinez-barrios, E., Sarquella-brugada, G., Perez-serra, A., Fernandez-falgueras, A., Cesar, S., Coll, M., Puigmule, M., Iglesias, A., Alcalde, M., Vallverdu-prats, M., Ferrer-costa, C., Del Olmo, B., Pico, F., Lopez, L., Fiol, V., Cruzalegui, J., Hernandez, C., Arbelo, E., Grassi, S., Oliva, Antonio, Toro, R., Brugada, J., Brugada, R., Campuzano, O., Oliva A. (ORCID:0000-0001-7120-616X), Martinez-barrios, E., Sarquella-brugada, G., Perez-serra, A., Fernandez-falgueras, A., Cesar, S., Coll, M., Puigmule, M., Iglesias, A., Alcalde, M., Vallverdu-prats, M., Ferrer-costa, C., Del Olmo, B., Pico, F., Lopez, L., Fiol, V., Cruzalegui, J., Hernandez, C., Arbelo, E., Grassi, S., Oliva, Antonio, Toro, R., Brugada, J., Brugada, R., Campuzano, O., and Oliva A. (ORCID:0000-0001-7120-616X)

Abstract

The titin gene (TTN) is associated with several diseases, including inherited arrhythmias. Most of these diagnoses are attributed to rare TTN variants encoding truncated forms, but missense variants represent a diagnostic challenge for clinical genetics. The proper interpretation of genetic data is critical for translation into the clinical setting. Notably, many TTN variants were classified before 2015, when the American College of Medical Genetics and Genomics (ACMG) published recommendations to accurately classify genetic variants. Our aim was to perform an exhaustive reanalysis of rare missense TTN variants that were classified before 2015, and that have ambiguous roles in inherited arrhythmogenic syndromes. Rare missense TTN variants classified before 2015 were updated following the ACMG recommendations and according to all the currently available data. Our cohort included 193 individuals definitively diagnosed with an inherited arrhythmogenic syndrome before 2015. Our analysis resulted in the reclassification of 36.8% of the missense variants from unknown to benign/likely benign. Of all the remaining variants, currently classified as of unknown significance, 38.3% showed a potential, but not confirmed, deleterious role. Most of these rare missense TTN variants with a suspected deleterious role were identified in patients diagnosed with hypertrophic cardiomyopathy. More than 35% of the rare missense TTN variants previously classified as ambiguous were reclassified as not deleterious, mainly because of improved population frequencies. Despite being inconclusive, almost 40% of the variants showed a potentially deleterious role in inherited arrhythmogenic syndromes. Our results highlight the importance of the periodical reclassification of rare missense TTN variants to improve genetic diagnoses and help increase the accuracy of personalized medicine.

Published
2022

16. Eficiencia y productividad en el comercio del sector manufacturero entre Venezuela y Mercosur

Author

Hugo R. Martínez C. and Jairo J. Pico F.

Subjects
Commerce, HF1-6182, Business, HF5001-6182
Abstract

El objetivo de la investigación fue determinar la eficiencia y la productividad del comercio del sector manufacturero entre Venezuela y el Mercosur durante el 1999-2009. El tipo de investigación fue explicativa con un diseño no experimental de corte transversal. La población estuvo constituida por unidades de decisión, en adelante (DMU) representadas por Venezuela, Brasil, Argentina, Paraguay y Uruguay. La técnica de recolección de datos fue documental. La técnica de análisis de datos utilizada, fue la metodología no paramétrica del Análisis Envolvente de Datos y el método del Índice de Malmquist. Los resultados indican que Venezuela muestra ineficiencia técnica de insumos con tendencia descendente entre 0,7% al 26,3%, Uruguay con 4,9% al 5,7%; Brasil y Paraguay se destacan debido al uso eficiente de recursos, Argentina en menor importancia. Venezuela fue la única que registró pérdidas de productividad en el comercio de manufacturas 0,102%, el resto avanzaron: Argentina crece con 2,13%, Brasil en 0,0234%, Paraguay en 0,2823% y Uruguay en 0,51%. Se concluye como prioridad que el país desarrolle condiciones de eficiencia y productividad para adelantar una mejor posición competitiva en ámbito internacional.

Published
2013

28. Rare variants associated with arrhythmogenic cardiomyopathy: Reclassification five years later

Author

Vallverdu-Prats, M., Alcalde, M., Sarquella-Brugada, G., Cesar, S., Arbelo, E., Fernandez-Falgueras, A., Coll, M., Perez-Serra, A., Puigmule, M., Iglesias, A., Fiol, V., Ferrer-Costa, C., Olmo, B., Pico, F., Lopez, L., Jorda, P., Garcia-alvarez, A., Llano, C. T., Toro, R., Grassi, S., Oliva, Antonio, Brugada, J., Brugada, R., Campuzano, O., Oliva A. (ORCID:0000-0001-7120-616X), Vallverdu-Prats, M., Alcalde, M., Sarquella-Brugada, G., Cesar, S., Arbelo, E., Fernandez-Falgueras, A., Coll, M., Perez-Serra, A., Puigmule, M., Iglesias, A., Fiol, V., Ferrer-Costa, C., Olmo, B., Pico, F., Lopez, L., Jorda, P., Garcia-alvarez, A., Llano, C. T., Toro, R., Grassi, S., Oliva, Antonio, Brugada, J., Brugada, R., Campuzano, O., and Oliva A. (ORCID:0000-0001-7120-616X)

Abstract

Genetic interpretation of rare variants associated with arrhythmogenic cardiomyopathy (ACM) is essential due to their diagnostic implications. New data may relabel previous variant classifications, but how often reanalysis is necessary remains undefined. Five years ago, 39 rare ACM-related variants were identified in patients with features of cardiomyopathy. These variants were classified following the American College of Medical Genetics and Genomics’ guidelines. In the present study, we reevaluated these rare variants including novel available data. All cases carried one rare variant classified as being of ambiguous significance (82.05%) or likely pathogenic (17.95%) in 2016. In our comprehensive reanalysis, the classification of 30.77% of these variants changed, mainly due to updated global frequencies. As in 2016, nowadays most variants were classified as having an uncertain role (64.1%), but the proportion of variants with an uncertain role was significantly decreased (17.95%). The percentage of rare variants classified as potentially del-eterious increased from 17.95% to 23.07%. Moreover, 83.33% of reclassified variants gained cer-tainty. We propose that periodic genetic reanalysis of all rare variants associated with arrhythmo-genic cardiomyopathy should be undertaken at least once every five years. Defining the roles of rare variants may help clinicians obtain a definite diagnosis.

Published
2021

30. Global Impact of COVID-19 on Stroke Care and IV Thrombolysis

Author

Nogueira, R.G. Qureshi, M.M. Abdalkader, M. Martins, S.O. Yamagami, H. Qiu, Z. Mansour, O.Y. Sathya, A. Czlonkowska, A. Tsivgoulis, G. Aguiar de Sousa, D. Demeestere, J. Mikulik, R. Vanacker, P. Siegler, J.E. Kõrv, J. Biller, J. Liang, C.W. Sangha, N.S. Zha, A.M. Czap, A.L. Holmstedt, C.A. Turan, T.N. Ntaios, G. Malhotra, K. Tayal, A. Loochtan, A. Ranta, A. Mistry, E.A. Alexandrov, A.W. Huang, D.Y. Yaghi, S. Raz, E. Sheth, S.A. Mohammaden, M.H. Frankel, M. Bila Lamou, E.G. Aref, H.M. Elbassiouny, A. Hassan, F. Menecie, T. Mustafa, W. Shokri, H.M. Roushdy, T. Sarfo, F.S. Alabi, T.O. Arabambi, B. Nwazor, E.O. Sunmonu, T.A. Wahab, K. Yaria, J. Mohammed, H.H. Adebayo, P.B. Riahi, A.D. Sassi, S.B. Gwaunza, L. Ngwende, G.W. Sahakyan, D. Rahman, A. Ai, Z. Bai, F. Duan, Z. Hao, Y. Huang, W. Li, G. Li, W. Liu, G. Luo, J. Shang, X. Sui, Y. Tian, L. Wen, H. Wu, B. Yan, Y. Yuan, Z. Zhang, H. Zhang, J. Zhao, W. Zi, W. Leung, T.W. Chugh, C. Huded, V. Menon, B. Pandian, J.D. Sylaja, P.N. Usman, F.S. Farhoudi, M. Hokmabadi, E.S. Horev, A. Reznik, A. Sivan Hoffmann, R. Ohara, N. Sakai, N. Watanabe, D. Yamamoto, R. Doijiri, R. Tokuda, N. Yamada, T. Terasaki, T. Yazawa, Y. Uwatoko, T. Dembo, T. Shimizu, H. Sugiura, Y. Miyashita, F. Fukuda, H. Miyake, K. Shimbo, J. Sugimura, Y. Yagita, Y. Takenobu, Y. Matsumaru, Y. Yamada, S. Kono, R. Kanamaru, T. Yamazaki, H. Sakaguchi, M. Todo, K. Yamamoto, N. Sonoda, K. Yoshida, T. Hashimoto, H. Nakahara, I. Kondybayeva, A. Faizullina, K. Kamenova, S. Zhanuzakov, M. Baek, J.-H. Hwang, Y. Lee, J.S. Lee, S.B. Moon, J. Park, H. Seo, J.H. Seo, K.-D. Sohn, S.I. Young, C.J. Ahdab, R. Wan Zaidi, W.A. Aziz, Z.A. Basri, H.B. Chung, L.W. Ibrahim, A.B. Ibrahim, K.A. Looi, I. Tan, W.Y. Yahya, N.W. Groppa, S. Leahu, P. Al Hashmi, A.M. Imam, Y.Z. Akhtar, N. Pineda-Franks, M.C. Co, C.O. Kandyba, D. Alhazzani, A. Al-Jehani, H. Tham, C.H. Mamauag, M.J. Venketasubramanian, N. Chen, C.-H. Tang, S.-C. Churojana, A. Akil, E. Aykaç, Ö. Ozdemir, A.O. Giray, S. Hussain, S.I. John, S. Le Vu, H. Tran, A.D. Nguyen, H.H. Nhu Pham, T. Nguyen, T.H. Nguyen, T.Q. Gattringer, T. Enzinger, C. Killer-Oberpfalzer, M. Bellante, F. De Blauwe, S. Vanhooren, G. De Raedt, S. Dusart, A. Lemmens, R. Ligot, N. Pierre Rutgers, M. Yperzeele, L. Alexiev, F. Sakelarova, T. Bedeković, M.R. Budincevic, H. Cindric, I. Hucika, Z. Ozretic, D. Saric, M.S. Pfeifer, F. Karpowic, I. Cernik, D. Sramek, M. Skoda, M. Hlavacova, H. Klecka, L. Koutny, M. Vaclavik, D. Skoda, O. Fiksa, J. Hanelova, K. Nevsimalova, M. Rezek, R. Prochazka, P. Krejstova, G. Neumann, J. Vachova, M. Brzezanski, H. Hlinovsky, D. Tenora, D. Jura, R. Jurák, L. Novak, J. Novak, A. Topinka, Z. Fibrich, P. Sobolova, H. Volny, O. Krarup Christensen, H. Drenck, N. Klingenberg Iversen, H. Simonsen, C.Z. Truelsen, T.C. Wienecke, T. Vibo, R. Gross-Paju, K. Toomsoo, T. Antsov, K. Caparros, F. Cordonnier, C. Dan, M. Faucheux, J.-M. Mechtouff, L. Eker, O. Lesaine, E. Ondze, B. Peres, R. Pico, F. Piotin, M. Pop, R. Rouanet, F. Gubeladze, T. Khinikadze, M. Lobjanidze, N. Tsiskaridze, A. Nagel, S. Ringleb, P.A. Rosenkranz, M. Schmidt, H. Sedghi, A. Siepmann, T. Szabo, K. Thomalla, G. Palaiodimou, L. Sagris, D. Kargiotis, O. Klivenyi, P. Szapary, L. Tarkanyi, G. Adami, A. Bandini, F. Calabresi, P. Frisullo, G. Renieri, L. Sangalli, D. Pirson, A. Uyttenboogaart, M. van den Wijngaard, I. Kristoffersen, E.S. Brola, W. Fudala, M. Horoch-Lyszczarek, E. Karlinski, M. Kazmierski, R. Kram, P. Rogoziewicz, M. Kaczorowski, R. Luchowski, P. Sienkiewicz-Jarosz, H. Sobolewski, P. Fryze, W. Wisniewska, A. Wiszniewska, M. Ferreira, P. Ferreira, P. Fonseca, L. Marto, J.P. Pinho E Melo, T. Nunes, A.P. Rodrigues, M. Tedim Cruz, V. Falup-Pecurariu, C. Krastev, G. Mako, M. de Leciñana, M.A. Arenillas, J.F. Ayo-Martin, O. Cruz Culebras, A. Tejedor, E.D. Montaner, J. Pérez-Sánchez, S. Tola Arribas, M.A. Rodriguez Vasquez, A. Mayza, M. Bernava, G. Brehm, A. Machi, P. Fischer, U. Gralla, J. Michel, P.L. Psychogios, M.-N. Strambo, D. Banerjee, S. Krishnan, K. Kwan, J. Butt, A. Catanese, L. Demchuk, A.M. Field, T. Haynes, J. Hill, M.D. Khosravani, H. Mackey, A. Pikula, A. Saposnik, G. Scott, C.A. Shoamanesh, A. Shuaib, A. Yip, S. Barboza, M.A. Barrientos, J.D. Portillo Rivera, L.I. Gongora-Rivera, F. Novarro-Escudero, N. Blanco, A. Abraham, M. Alsbrook, D. Altschul, D. Alvarado-Ortiz, A.J. Bach, I. Badruddin, A. Barazangi, N. Brereton, C. Castonguay, A. Chaturvedi, S. Chaudry, S.A. Choe, H. Choi, J.H. Dharmadhikari, S. Desai, K. Devlin, T.G. Doss, V.T. Edgell, R. Etherton, M. Farooqui, M. Frei, D. Gandhi, D. Grigoryan, M. Gupta, R. Hassan, A.E. Helenius, J. Kaliaev, A. Kaushal, R. Khandelwal, P. Khawaja, A.M. Khoury, N.N. Kim, B.S. Kleindorfer, D.O. Koyfman, F. Lee, V.H. Leung, L.Y. Linares, G. Linfante, I. Lutsep, H.L. Macdougall, L. Male, S. Malik, A.M. Masoud, H. McDermott, M. Mehta, B.P. Min, J. Mittal, M. Morris, J.G. Multani, S.S. Nahab, F. Nalleballe, K. Nguyen, C.B. Novakovic-White, R. Ortega-Gutierrez, S. Rahangdale, R.H. Ramakrishnan, P. Romero, J.R. Rost, N. Rothstein, A. Ruland, S. Shah, R. Sharma, M. Silver, B. Simmons, M. Singh, A. Starosciak, A.K. Strasser, S.L. Szeder, V. Teleb, M. Tsai, J.P. Voetsch, B. Balaguera, O. Pujol Lereis, V.A. Luraschi, A. Almeida, M.S. Cardoso, F.B. Conforto, A. De Deus Silva, L. Varrone Giacomini, L. Oliveira Lima, F. Longo, A.L. Magalhães, P.S.C. Martins, R.T. Mont'alverne, F. Mora Cuervo, D.L. Costa Rebello, L. Valler, L. Zetola, V.F. Lavados, P.M. Navia, V. Olavarría, V.V. Almeida Toro, J.M. Amaya, P.F.R. Bayona, H. Corredor, A. Rivera Ordonez, C.E. Mantilla Barbosa, D.K. Lara, O. Patiño, M.R. Diaz Escobar, L.F. Dejesus Melgarejo Fariña, D.E. Cardozo Villamayor, A. Zelaya Zarza, A.J. Barrientos Iman, D.M. Rodriguez Kadota, L. Campbell, B. Hankey, G.J. Hair, C. Kleinig, T. Ma, A. Tomazini Martins, R. Sahathevan, R. Thijs, V. Salazar, D. Yuan-Hao Wu, T. Haussen, D.C. Liebeskind, D. Yavagal, D.R. Jovin, T.G. Zaidat, O.O. Nguyen, T.N. SVIN COVID-19 Global Stroke Registry SVIN COVID-19 Global Stroke Registry

Abstract

OBJECTIVE: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods. METHODS: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. RESULTS: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] -11.7 to -11.3, p < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI -13.8 to -12.7, p < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI -13.7 to -10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2-9.8, p < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions. CONCLUSIONS: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months. © 2021 American Academy of Neurology.

Published
2021

32. Natural genetic variation of Arabidopsis thaliana is geographically structured in the Iberian peninsula

Author

Pico, F. Xavier, Mendez-Vigo, Belen, Martinez-Zapater, Jose M., and Alonso-Blanco, Carlos

Subjects
Iberian Peninsula -- Environmental aspects, Arabidopsis thaliana -- Genetic aspects, Arabidopsis thaliana -- Distribution, Genetic variation -- Evaluation, Genetic research, Company distribution practices, Biological sciences
Abstract

To understand the demographic history of Arabidopsis thaliana within its native geographical range, we have studied its genetic structure in the Iberian Peninsula region. We have analyzed the amount and spatial distribution of A. thaliana genetic variation by genotyping 268 individuals sampled in 100 natural populations from the Iberian Peninsula. Analyses of 175 individuals from 7 of these populations, with 20 chloroplast and nuclear microsatellite loci and 109 common single nucleotide polymorphisms, show significant population differentiation and isolation by distance. In addition, analyses of one genotype from 100 populations detected significant isolation by distance over the entire Iberian Peninsula, as well as among six Iberian subregions. Analyses of these 100 genotypes with different model-based clustering algorithms inferred four genetic clusters, which show a clear-cut geographical differentiation pattern. On the other hand, clustering analysis of a worldwide sample showed a west-east Eurasian longitudinal spatial gradient of the commonest Iberian genetic cluster. These results indicate that A. thaliana genetic variation displays significant regional structure and consistently support the hypothesis that Iberia has been a glacial refugium for A. thaliana. Furthermore, the Iberian geographical structure indicates a complex regional population dynamics, suggesting that this region contained multiple Pleistocene refugia with a different contribution to the postglacial colonization of Europe.

Published
2008

33. A Comparison of Two LDL Cholesterol Targets after Ischemic Stroke

Author

Amarenco P, Kim J, Labreuche J, Charles H, Abtan J, Bejot Y, Cabrejo L, Cha J, Ducrocq G, Giroud M, Guidoux C, Hobeanu C, Kim Y, Lapergue B, Lavallee P, Lee B, Lee K, Leys D, Mahagne M, Meseguer E, Nighoghossian N, Pico F, Samson Y, Sibon I, Steg P, Sung S, Touboul P, Touze E, Varenne O, Vicaut E, Yelles N, Bruckert E, Treat Stroke Target Investigators, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Asan Medical Center [Seoul], University of Ulsan, Santé Publique : épidémiologie et qualité des soins (EA 2694), Faculté de Médecine Henri Warembourg - Université de Lille-Centre d'Etudes et de Recherche en Informatique Médicale [Lille] (CERIM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université de Bourgogne (UB), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Catholic University of Korea, Hôpital Foch [Suresnes], Hallym University Sacred Heart Hospital [Anyang, South Korea] (HUS2H), Soonchunhyang University [Asan], CHU Lille, Hôpital Pasteur [Nice] (CHU), Hospices Civils de Lyon (HCL), Centre Hospitalier de Versailles André Mignot (CHV), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Pusan National University Hospital, Physiopathologie et imagerie des troubles neurologiques (PhIND), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), GIP Cyceron (Cyceron), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Cardiologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559 (LNFP), Université de Picardie Jules Verne (UPJV), CHU Amiens-Picardie, and Treat Stroke to Target Investigators: Pierre Amarenco, Eric Bruckert, Maurice Giroud, Jong S Kim, Julien Labreuche, Byung-Chul Lee, Marie-Hélène Mahagne, Norbert Nighoghossian, Philippe Gabriel Steg, Pierre-Jean Touboul, Eric Vicaut, Didier Leys, Philippa Lavallée, Gregory Ducrocq, Jérémy Abtan, Olivier Varenne, Agnes Kemmel, Fausta Syana, Manele Ledra, Tharani Nagasara, Mervette Ledjeroud, Bahous Samia, Hafirassou Hadia, Benyoub Hazare, Ikrame El Jaghouni, Nessima Yelles, Sofia Zemouri, Mervette Ladjeroud, Salim Kerai, YunJeong In, Elena Meseguer, Philippa C Lavallée, Cristina Hobeanu, Celine Guidoux, Lucie Cabrejo, Jaime Gonzalez-Valcarcel, Ricardo Rigual, Gaia Sirimarco, Anna Martin-Bechet, Elena Viedma, Ioan Avram, Yves Samson, Charlotte Rosso, Sophie Crozier, Sara Leder, Anne Léger, Sandrine Deltour, Chiara Zavanone, Flore Baronnet, Christine Pires, Bertrand Lapergue, Adrien Wang, Serge Evrard, Maya Tchikviladze, Frédéric Bourdain, Delphine Lopez, Fernando Pico, Laetitia Bayon de la Tour, Marie-Laure Chadenat, Duc Long Duong, Solène Genty, Catherine Hirel, Gurkan Mutlu, Chantal Nifle, Jérôme Servan, Daniela Stanciu, Veronica Sudacevschi, Mélissa Tir, Anne-Cécile Troussière, Jennifer Yeung, Anne-Céline Zeghoudi, Ikram Tidafi-Bayou, Sylvain Lachaud, Tae-Hee Cho, Laura Mechtouff, Thomas Ritzenthaller, Laurent Derex, Carlo Albanesi, Elodie Ong, Amandine Benoit, Nadia Berhoune, Sandra Felix, Maud Esteban-Mader, Igor Sibon, Annabelle Kazadi, François Rouanet, Pauline Renou, Sabrina Debruxelles, Mathilde Poli, Sharmila Sagnier, Jean-Louis Mas, Valérie Domigo, Catherine Lamy, Eric Bodiguel, Jérôme Grimaud, Valentin Bohotin, Michael Obadia, Candice Sabben, Erwan Morvan, Gilles Rodier, Wilfried Vadot, Hilde Hénon, Charlotte Cordonnier, Frédéric Dumont, Marie Bodenant, Christian Lucas, Solène Moulin, Nelly Dequatre, Sonia Alamowitch, Jean-Paul Muresan, Thomas Drouet, Magalie Gallea, Marie-Amélie Dalloz, Stephen Delorme, Marion Yger, Yannick Béjot, Philippe Loisel, Carine Bonnin, Virginie Bernigal, Guy Victor Osseby, Marie Hervieu-BègueMarsac, Pierre Garnier, Sandrine Accassat, Magali Epinat, Jérôme Varvat, Doïna Marinescu, Aude Triquenot-Bagan, Ozlem Ozkul-Wermester, Frédéric Philippeau, Angel Olaru, Anne Vieillart, Annie Lannuzel, Alice Demoly, Valérie Wolff, Mihaela Diaconu, Francisco Macian Montoro, Frédéric Faugeras, Laeticia Gimenez, Françoise Abdallah-Lebeau, Serge Timsit, Irina Viakhireva-Dovganyuk, Anne Tirel-Badets, François-Mathias Merrien, Philippe Goas, François Rouhart, Aurore Jourdain, Benoit Guillon, Fanny Hérissson, Mathieu Sevin-Allouet, Nathalie Nasr, Jean-Marc Olivot, Alderic Lecluse, Guillaume Marc, Emmanuel Touzé, Vincent de la Sayette, Marion Apoil, Li Lin, Julien Cogez, Sophie Guettier, Olivier Godefroy, Chantal Lamy, Jean-Marc Bugnicourt, Grégory Taurin, Marc Mérienne, Julien Gere, Anne-Marie Chessak, Tarik Habet, Anna Ferrier, Nathalie Bourgois, Dominique Minier, Marie Caillier-Minier, Fabienne Contégal-Callier, Philippe Vion, Yvan Vaschalde, Mohammed El Amrani, Mathieu Zuber, Marie Bruandet, Claire Join-Lambert, Pierre-Yves Garcia, Isabelle Serre, Jean-Marc Faucheux, Fatia Radji, Elena Leca-Radu, Thomas Debroucker, Rodica Cumurcuc, Serkan Cakmak, Stéphane Peysson, Emmanuel Ellie, Patricia Bernady, Thierry Moulin, Paola Montiel, Eugeniu Revenco, Pierre Decavel, Elisabeth Medeiros, Myriam Bouveret, Pierre Louchart, Claudia Vaduva, Grégory Couvreur, Eric Sartori, Adam Amer Alnajar-Carpentier, Michèle Levasseur, Pierre Louchart, Jean-Philippe Neau, Xavier Vandamme, Isabelle Meresse, Marc Bataillard, Canan Ozsancak, Katell Beauvais, Pascal Auzou, Joséphine Amevigbe, Francis Vuillemet, Marie-Hélène Dugay-Arentz, Gabriela Carelli, Mikel Martinez, Marcel Maillet-Vioud, Jean-Pierre Escaillas, Stéphane Chapuis, Jean Tardy, Eric Manchon, Olivier Varnet, Yong-Jae Kim, Yoonkyung Chang, Tae-Jin Song, Jong Sung Kim, Jung-Hoon Han, Kyung Chul Noh, Eun-Jae Lee, Dong-Wha Kang, Sun Uck Kwon, Boseoung Kwon, Seongho Park, Dongwhane Lee, Hyuk Sung Kwon, Daeun Jeong, MinHwan Lee, Joonggoo Kim, Hanbin Lee, Hyo Jung Nam, Sang Hun Lee, Bum Joon Kim, Jae-Kwan Cha, DaeHyun Kim, Rae Young Kim, Sang Wuk Sohn, Dong-Hyun Shim, Hyungjin Lee, Hyun-Wook Nah, Sang Min Sung, Kyung Bok Lee, Jeong Yoon Lee, Jee Eun Yoon, Eung-Gyu Kim, Jung Hwa Seo, Yong-Won Kim, Yangha Hwang, Man Seok Park, Joon-Tae Kim, Kang-Ho Choi, Hyo Suk Nam, Ji Hoe Heo, Young Dae Kim, In Gun Hwang, Hyung Jong Park, Kyoung Sub Kim, Jang Hyun Baek, Dong Beom Song, Joon Sang Yoo, Jong-Moo Park, Ohyun Kwon, Woong-Woo Lee, Jung-Ju Lee, Kyusik Kang, Byung Kun Kim, Jae-Sung Lim, Mi Sun Oh, Kyung-Ho Yu, Bora Hong, Mihoon Jang, Seyoung Jang, Jung Eun Jin, Jei Kim, Hye Seon Jeong, Keun Sik Hong, Hong Kyun Park, Yong Jin Cho, Oh Young Bang, Woo-Keun Seo, Jongwon Chung

Subjects
Adult, Male, medicine.medical_specialty, Statin, medicine.drug_class, [SDV]Life Sciences [q-bio], MEDLINE, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Brain Ischemia, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Text mining, Pharmacotherapy, Randomized controlled trial, law, Internal medicine, Humans, Medicine, cardiovascular diseases, 030212 general & internal medicine, Aged, Intention-to-treat analysis, business.industry, Cholesterol, Anticholesteremic Agents, Cholesterol, LDL, General Medicine, Middle Aged, Atherosclerosis, Ezetimibe, Intention to Treat Analysis, Stroke, chemistry, Cardiovascular Diseases, Ischemic Attack, Transient, Ischemic stroke, Drug Therapy, Combination, Female, lipids (amino acids, peptides, and proteins), Hydroxymethylglutaryl-CoA Reductase Inhibitors, business
Abstract

International audience; BACKGROUND: The use of intensive lipid-lowering therapy by means of statin medications is recommended after transient ischemic attack (TIA) and ischemic stroke of atherosclerotic origin. The target level for low-density lipoprotein (LDL) cholesterol to reduce cardiovascular events after stroke has not been well studied. METHODS: In this parallel-group trial conducted in France and South Korea, we randomly assigned patients with ischemic stroke in the previous 3 months or a TIA within the previous 15 days to a target LDL cholesterol level of less than 70 mg per deciliter (1.8 mmol per liter) (lower-target group) or to a target range of 90 mg to 110 mg per deciliter (2.3 to 2.8 mmol per liter) (higher-target group). All the patients had evidence of cerebrovascular or coronary-artery atherosclerosis and received a statin, ezetimibe, or both. The composite primary end point of major cardiovascular events included ischemic stroke, myocardial infarction, new symptoms leading to urgent coronary or carotid revascularization, or death from cardiovascular causes. RESULTS: A total of 2860 patients were enrolled and followed for a median of 3.5 years; 1430 were assigned to each LDL cholesterol target group. The mean LDL cholesterol level at baseline was 135 mg per deciliter (3.5 mmol per liter), and the mean achieved LDL cholesterol level was 65 mg per deciliter (1.7 mmol per liter) in the lower-target group and 96 mg per deciliter (2.5 mmol per liter) in the higher-target group. The trial was stopped for administrative reasons after 277 of an anticipated 385 end-point events had occurred. The composite primary end point occurred in 121 patients (8.5%) in the lower-target group and in 156 (10.9%) in the higher-target group (adjusted hazard ratio, 0.78; 95% confidence interval, 0.61 to 0.98; P = 0.04). The incidence of intracranial hemorrhage and newly diagnosed diabetes did not differ significantly between the two groups. CONCLUSIONS: After an ischemic stroke or TIA with evidence of atherosclerosis, patients who had a target LDL cholesterol level of less than 70 mg per deciliter had a lower risk of subsequent cardiovascular events than those who had a target range of 90 mg to 110 mg per deciliter. (Funded by the French Ministry of Health and others; Treat Stroke to Target ClinicalTrials.gov number, NCT01252875.).

Published
2020

34. Sudden Cardiac Death and Copy Number Variants: What Do We Know after 10 Years of Genetic Analysis?

Author

Mates, J., Mademont-Soler, I., Fernandez-Falgueras, A., Sarquella-Brugada, G., Cesar, S., Arbelo, E., Garcia-Alvarez, A., Jorda, P., Toro, R., Coll, M., Fiol, V., Iglesias, A., Perez-Serra, A., Olmo, B. D., Alcalde, M., Puigmule, M., Pico, F., Lopez, L., Ferrer, C., Tiron, C., Grassi, S., Oliva, Antonio, Brugada, J., Brugada, R., Campuzano, O., Oliva A. (ORCID:0000-0001-7120-616X), Mates, J., Mademont-Soler, I., Fernandez-Falgueras, A., Sarquella-Brugada, G., Cesar, S., Arbelo, E., Garcia-Alvarez, A., Jorda, P., Toro, R., Coll, M., Fiol, V., Iglesias, A., Perez-Serra, A., Olmo, B. D., Alcalde, M., Puigmule, M., Pico, F., Lopez, L., Ferrer, C., Tiron, C., Grassi, S., Oliva, Antonio, Brugada, J., Brugada, R., Campuzano, O., and Oliva A. (ORCID:0000-0001-7120-616X)

Abstract

Over the last ten years, analysis of copy number variants has increasingly been applied to the study of arrhythmogenic pathologies associated with sudden death, mainly due to significant advances in the field of massive genetic sequencing. Nevertheless, few published reports have focused on the prevalence of copy number variants associated with sudden cardiac death. As a result, the frequency of these genetic alterations in arrhythmogenic diseases as well as their genetic interpretation and clinical translation has not been established. This review summarizes the current available data concerning copy number variants in sudden cardiac death-related diseases.

Published
2020

35. Ramet demography of a nurse bromeliad in Brazilian restingas

Author

Sampaio, Michelle C., Pico, F. Xavier, and Scarano, Fabio R.

Subjects
Plant life cycles -- Research, Plant population genetics -- Analysis, Bromeliaceae -- Research, Biological sciences
Abstract

Restingas are sandy coastal plains that stand between the sea and the Brazilian Atlantic forest mountains. The predominant restinga vegetation type in northern Rio de Janeiro, Brazil, is characterized by the formation of islands that begins with colonization by some pioneer herbs and/or woody plants. Pioneer plants are stress-resistant and nurse many other less-resistant plant species. Determining the spatiotemporal variation in the dynamics of nurse plants is essential to understand the ecological functioning of restingas as a whole. The goal of this study was to analyze the spatiotemporal variation in population dynamics of the nurse bromeliad Aechmea nudicaulis. We monitored A. nudicaulis ramets in different habitats, microhabitats, and years. We analyzed the spatiotemporal variation in demographic traits and in population growth rate. Results showed young ramet traits were more variable at the microhabitat level, and when variable, vegetative ramet traits varied at all spatiotemporal scales. Overall, [lambda] values indicated that A. nudicaulis basically remained spatiotemporally stable as most of the h values did not significantly differ from unity. Hence, the stability of A. nudicaulis in different microhabitats and habitats in the restinga may create several settlement opportunities for many other less-resistant species. Key words: Aechmea nudicaulis; Brazil; Bromeliaceae; life-cycle traits; nurse plants; population dynamics; restinga.

Published
2005

36. Short QT Syndrome: A Comprehensive Genetic Interpretation and Clinical Translation of Rare Variants

Author

Campuzano O, Fernandez-Falgueras A, Lemus X, Sarquella-Brugada G, César, S., Coll M, Mates J, Arbelo E, Jordà P, Perez-Serra A, Del Olmo B, Ferrer-Costa C, Iglesias A, Fiol JV, Puigmulé M, Lopez L, Pico F, Brugada-Terradellas J, and Brugada R

Subjects
short QT syndrome, pathogenicity, genetics, sudden cardiac death
Abstract

Short QT syndrome, one of the most lethal entities associated with sudden cardiac death, is a rare genetic disease characterized by short QT intervals detected by electrocardiogram. Several genetic variants are causally linked to the disease, but there has yet to be a comprehensive analysis of variants among patients with short QT syndrome. To fill this gap, we performed an exhaustive study of variants currently catalogued as deleterious in short QT syndrome according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Analysis of the 32 variants described in the literature determined that only nine (28.12%) have a conclusive pathogenic role. All definitively pathogenic variants are located in KCNQ1, KCNH2, or KCNJ2; three genes encoding potassium channels. Other variants located in genes encoding calcium or sodium channels are associated with electrical alterations concomitant with shortened QT intervals but do not guarantee a diagnosis of short QT syndrome. We recommend caution regarding previously reported variants classified as pathogenic. An exhaustive re-analysis is necessary to clarify the role of each variant before routinely translating genetic findings to the clinical setting.

Published
2019

37. Rivaroxaban for stroke prevention after embolic stroke of undetermined source

Author

Hart, Robert G, Sharma, Mukul, Mundl, Hardi, Kasner, Scott E, Bangdiwala, Shrikant I, Berkowitz, Scott D, Swaminathan, Balakumar, Lavados, Pablo, Wang, Yongjun, Wang, Yilong, Davalos, Antonio, Shamalov, Nikolay, Mikulik, Robert, Cunha, Luis, Lindgren, Arne, Arauz, Antonio, Lang, Wilfried, Czlonkowska, Anna, Eckstein, Jens, Gagliardi, Rubens J, Amarenco, Pierre, Ameriso, Sebastian F, Tatlisumak, Turgut, Veltkamp, Roland, Hankey, Graeme J, Toni, Danilo, Bereczki, Daniel, Uchiyama, Shinichiro, Ntaios, George, Yoon, Byung-Woo, Brouns, Raf, Endres, Matthias, Muir, Keith W, Bornstein, Natan, Ozturk, Serefnur, O'Donnell, Martin J, De Vries Basson, Matthys M, Pare, Guillaume, Pater, Calin, Kirsch, Bodo, Sheridan, Patrick, Peters, Gary, Weitz, Jeffrey I, Peacock, W Frank, Shoamanesh, Ashkan, Benavente, Oscar R, Joyner, Campbell, Themeles, Ellison, Connolly, Anderson DC, Stuart J., Demets, Dl, Kaste, M, Norrving, B, Wyse, Dg, Alet, M, Allende, G, Beinlich, A, Berrios, W, Bruera, G, Castro, D, Chialvo, L, Claverie, S, Contardo, L, Couto, J, Deganutto, R, Diaz, R, Dossi, D, Esnaola, M, Falco, M, Fernandez Pirrone, P, Ferrari, J, Firstenfeld, A, Galli Giqueauk, E, Gilli, M, Gonzalez, L, Gonzalez Toledo, M, Grecco, M, Halac, B, Hawkes, M, Ioli, P, Jure, L, Klein, F, Lepera, S, Lujan, S, Mackinnon, F, Marroquin, M, Martin, J, Parisi, V, Perez Leguizamon, P, Persi, G, Povedano, P, Povedano, G, Pujol Lereis, V, Radrizzani, L, Reich, E, Repetto, M, Rodriguez Lucci, F, Romano, M, Saredo, G, Schneider, M, Simonsini, C, Sumay, G, Thomson, A, Toledo, W, Torres, C, Vila, A, Abdul Rasheed, N, Anderson, C, Bailey, P, Blacker, D, Carcel, C, Clissold, B, Delcourt, C, Field, D, Gangadharan, S, Ghia, D, Kleinig, T, Leyden, J, Ly, J, Ma, H, Mackey, E, Mishra, S, Moey, A, Musuka, T, Pepper, E, Phan, T, Sabet, A, Saw, J, Singh, B, Tryambake, D, Tu, H, Wijeratne, T, Wong, A, Augustin, S, Esterbauer, M, Garnauf, M, Gasiorek, K, Gasser, S, Gaugg, M, Greisenegger, S, Harrasser, M, Heine, M, Huber, B, Joachim, B, Kapeller, P, Krebs, S, Kreuzpointer, R, Kunzmann, J, Lechner, H, Lohninger, B, Luschin, G, Macher, S, Marko, M, Matosevic, B, Mayr, A, Mismas, A, Mitrovic, N, Mutzenbach, J, Oberndorfer, S, Obmann, S, Raffelsberger, T, Roesler, C, Salletmayr, T, Serles, W, Stadler, K, Tinchon, A, Tolino, M, Verocai, V, Vigl, M, Voglsperger, B, Weber, J, Werner, P, Windt, J, Winkler, A, Wurzinger, H, Zelenka, I, Cras, P, Crols, R, De Keyser, J, De Klippel, N, De Pauw, A, De Smedt, A, Dhollander, I, Hermans, S, Ligot, N, Maqueda, V, Maqueda Maqueda, V, Naeije, G, Seynaeve, L, Soors, P, Van Daele, W, Vanacker, P, Vanderschueren, G, Willems, C, Yperzeele, L, Avelar, W, Bacellar, A, Batista, C, Bazan, R, Braga, G, Cardoso, F, Dagnino, M, Fabio, S, Ferreira Junior, G, Freitas, G, Friedrich, M, Gomes Neto, A, Guarda, S, Katsurayama, M, Machado, M, Martins, S, Meira, F, Minelli, C, Morais, R, Moro, C, Neto, O, Polin, M, Silva, D, Weiss, G, Basile, V, Beaudry, M, Berlingieri, J, Blacquiere, D, Buck, B, Chan, R, Coutts, S, Das, S, Desai, J, Ehrensperger, E, Field, T, Gladstone, D, Hachinski, V, Hassan, A, Hegedus, J, Hill, M, Jin, A, Khaw, A, Mackey, A, Maclean, G, Mandzia, J, Mann, S, Mehdiratta, M, Murphy, C, Ng, K, Oczkowski, W, Penn, A, Perera, K, Perez, Y, Pesant, Y, Phillips, S, Poppe, A, Sahlas, J, Shuaib, A, Spence, D, Sposato, L, Stotts, G, Tamayo, A, Teal, P, Wilson, L, Winder, T, Yegappan, C, Yip, S, Andreu, D, Araya, P, Bustamante, G, Figueroa, C, Gasic, K, Herrero, D, Matamala, G, Munoz, S, Olavarria, V, Pasten, J, Polanco, J, Reyes, P, Roldan, A, Salamanca, P, Silva, P, Toloza, C, Verdugo, M, Cai, K, Che, C, Chen, J, Chen, Z, Chen, T, Chen, H, Chen, X, Chen, B, Chen, G, Chen, L, Chu, F, Cui, L, Dai, C, Ding, N, Ding, J, Du, P, Du, J, Fang, L, Feng, J, Gao, Y, Geng, J, Guan, J, Hao, L, Huang, D, Huang, H, Jin, X, Jing, P, Ke, K, Li, G, Li, M, Li, S, Li, J, Liang, Z, Lin, H, Liu, K, Liu, X, Lu, Z, Ma, C, Pei, H, Qiu, J, Qu, X, Shen, W, Sun, X, Tian, J, Tong, L, Tong, Z, Wang, J, Wang, L, Wang, X, Wang, W, Wang, N, Wang, D, Wang, H, Wen, G, Weng, G, Wu, W, Wu, S, Xiao, B, Xiaopeng, W, Xiong, L, Xiong, Y, Xu, Y, Xu, J, Xu, Z, Yang, L, Yang, Y, Yang, X, Yang, J, Yang, Q, Yang, B, Zhang, C, Zhang, B, Zhang, Y, Zhang, S, Zhang, M, Zhang, X, Zhang, J, Zhao, L, Zhou, L, Bar, M, Barteys, M, Bartolottiova, T, Carek, M, Ferencova, K, Fiksa, J, Gallo, J, Goldemund, D, Hanouskova, L, Herzig, R, Hon, P, Jankovych, J, Jura, R, Kadlcikova, J, Kemlink, D, Kopecky, S, Krajickova, D, Kral, M, Krejci, V, Pavlik, O, Peisker, T, Pernicka, M, Peska, S, Rapantova, P, Reif, M, Rekova, P, Sanak, D, Sebejova, M, Skoda, O, Slonkova, J, Stetkarova, I, Tenora, D, Tumova, R, Vaclavik, D, Vasko, P, Veverka, T, Vitkova, E, Volna, J, Andersen, G, Christensen, H, Christensen, T, Damgaard, D, Iversen, H, Krarup Hansen, C, Kruuse, C, Martinussen, M, Modrau, B, Murtuzova, A, Ovesen, C, Papina, M, Svaneborg, N, Von Weitzel-Mudersbach, P, Curtze, S, Fanta, S, Huhtakangas, J, Keskinarkaus, I, Kivioja, R, Koivu, M, Korpela, J, Larjo, T, Linna, M, Marinkovic, I, Martinez-Majander, N, Nieminen, T, Nikkanen, M, Numminen, H, Ortiz, R, Österlund-Tauriala, E, Roine, R, Roine, S, Ruuskanen, J, Saarinen, J, Shulga, A, Sibolt, G, Tapanainen, A, Tapiola, T, Tiainen, M, Tomppo, L, Tumpula, O, Tuomainen, P, Tynkkynen, J, Vainikka, S, Valpas, J, Virta, J, Ylikallio, E, Ylikotila, P, Accassat, S, Aniculaesei, A, Baronnet, F, Bejot, Y, Bindila, D, Birchenall, J, Blanc-Labarre, C, Bodiguel, E, Bouly, S, Cabrejo, L, Calvet, D, Corlobe, A, Crozier, S, Delpont, B, Deltour, S, Diaconu, M, Domigo, V, Epinat, M, Ferreira, A, Fisselier, M, Garnier, P, Gimenez, L, Gueguen, A, Guidoux, C, Guillon, B, Guiraudg, V, Hervieu-Begue, M, Hobeanu, M, Khoumri, C, Lamy, C, Lauer, V, Le Bouc, R, Lecouturier, K, Leder, S, Leger, A, Macian-Montoro, F, Meseguer, E, Morar-Precup, D, Morvan, T, Morvan, E, Obadia, M, Osseby, G, Philippi, S, Pico, F, Quenardelle, V, Reiner, P, Rigual, R, Rosso, C, 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Wester, P, Arnold, M, Baumgartner, P, Beer, J, Bicker, H, Boos, L, Cereda, C, Chaloulos-Iakovidis, P, Christian, L, Engelter, S, Fisch, L, Fischer, U, Frey, S, Frick, M, Hauk, M, Hoffmann, M, Kahles, T, Manno, C, Medlin, F, Mircea, D, Nedeltchev, K, Panos, L, Polymeris, A, Schillinger, N, Stocker, R, Sztajzel, R, Alaydin, H, Batur Caglayan, H, Colakoglu, S, Demirci, N, Duman, T, Eren, F, Gokce, M, Inanc, Y, Nazliel, B, Ongun, G, Ozcekic Demirhan, S, Ozyurt, E, Selcuk, D, Sorgun, M, Tezcan, S, Togay Isikay, C, Tokgoz, O, Ulku Acar, R, Uluduz Ugurlu, D, Abdul-Saheb, M, Ahmad, N, Ali, A, Alwis, L, Balogun, I, Bathula, R, Behnam, Y, Bhandari, M, Bhargavah, M, Black, T, Blank, C, Bruce, D, Burn, M, Canepa, C, Chakrabarti, A, Chandrasena, D, Chembala, J, Cheripelli, B, Clarke, R, Cohen, D, Collas, D, Constantin, C, Dani, K, Del Giudice, A, Dennis, M, Devine, J, Dima, S, Doubal, F, Duodu, Y, Dutta, D, El Ta Wil, S, Elyas, S, Evans, N, Eveson, D, Fotherby, K, France, E, Furnace, J, Grabowski, S, Gunathilagan, G, Gutierrez, R, Guyler, P, Hargroves, D, Harkness, K, Harvey, M, Hayhoe, H, Hicken, L, Hussain, M, Kelly, S, Lam, M, Lindert, R, Louw, S, Luder, R, Macleod, M, Majid, A, Mangion, D, Markova, S, Markus, H, Marsh, R, Mcarthur, K, Menon, N, Metcalf, K, Minhas, J, Minns, M, Mistri, A, Moreton, F, Mpelembue, M, Muddegowda, G, Mudhar, O, Musarrat, K, Myint, M, Natarajan, I, Naylor, D, Ngeh, J, Papavasileiou, V, Perry, R, Piechowski-Jozwiak, B, Pradhan, M, Rani, A, Rashed, K, Robinson, T, Roffe, C, Saksena, R, Sattar, N, Sekaran, L, Selvarajah, J, Shah, S, Sinha, D, Sivakumar, R, Sztriha, L, Walters, D, Webb, T, Werring, D, Whiteley, W, Whiting, R, Abdelhamid, N, Abdul Rahman, D, Amin, H, Androulakis, M, Babikian, V, Baker, M, Barker Trejo, S, Benjamin, A, Birnbaum, L, Burke, J, Chen, S, Clark, W, Coull, B, De Havenon, A, Dearborn, J, Degeorgia, M, Essa, B, Fares, M, Favate, A, Furlan, A, Gebreyohanns, M, Goddeau, R, Green, D, Greer, D, Haralur Sreekantaiah, Y, Hasan, R, Hedna, V, Henninger, N, Holmstedt, C, Ishida, K, Jagolino, A, Johnson, M, Jun-Oconnell, A, Kaur, S, Khanna, A, Kirshner, H, Kittner, S, Kleindorfer, D, Leira, E, Loomis, C, Lord, A, Lowenkopf, T, Lutsep, H, Magadan, A, Majjhoo, A, Maud, A, Mayasi, Y, Mccullough, L, Mckinney, J, Mehta, S, Mehta, D, Mehta, B, Messe, S, Miller, B, Milling, T, Moonis, M, Navaratnam, D, Okpala, M, Patel, N, Pettigrew, L, Phinney, T, Ramos-Estebanez, C, Rasmussen, J, Rodriguez, G, Rybinnik, I, Santiago, P, Sarraj, A, Savitz, S, Sawyer, R, Scandura, T, Schindler, J, Sen, S, Shang, T, Sharrief, A, Sila, C, Simpkins, A, Sundararajan, S, Talahma, M, Tayal, A, Thaler, D, Tirschwell, D, Torres, J, Vora, N, Warnack, W, Waters, M, Wilson, C, Xiong, W, Zweifler, R, Zanferrari, C., St Marys Development Trust, Servicio de Neurologia (SANTIAGO - Neurologie), Universidad del Desarrollo, Department of Neurology (Dep Neuro - BEIJING), Tiantan Hospital, Neurology department, Universidade de Coimbra [Coimbra], Department of Internal Medicine, University Hospital Basel [Basel], Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Neurological Sciences, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Department of Neurology, Seoul National University Hospital, Institute of Neurosciences and Psychology [Glasgow], University of Glasgow, Neurology Department, Ichilov Medical Center, CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, Yperzeele, Laetitia, NAVIGATE ESUS Investigators, and Selçuk Üniversitesi

Subjects
Stroke/etiology, Male, [SDV]Life Sciences [q-bio], Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Brain Ischemia, Brain ischemia, 0302 clinical medicine, DESIGN, Rivaroxaban, Hemorrhage/chemically induced, Secondary Prevention, Medicine, Factor Xa Inhibitors/adverse effects, Stroke, Rivaroxaban/adverse effects, ComputingMilieux_MISCELLANEOUS, 11 Medical and Health Sciences, Aspirin, Atrial fibrillation, General Medicine, FORAMEN OVALE CLOSURE, Middle Aged, TRIALS, Intracranial Embolism, SAFETY, Aged, Factor Xa Inhibitors, Female, Hemorrhage, Humans, Platelet Aggregation Inhibitors, Medicine (all), Cardiology, Foramen ovale closure, Platelet aggregation inhibitor, Settore MED/26 - Neurologia, Life Sciences & Biomedicine, medicine.drug, medicine.medical_specialty, Platelet Aggregation Inhibitors/adverse effects, ANTITHROMBOTIC THERAPY, Aspirin/adverse effects, WARFARIN, 03 medical and health sciences, Secondary Prevention/methods, Medicine, General & Internal, Internal medicine, Intracranial Embolism/drug therapy, General & Internal Medicine, NAVIGATE ESUS Investigators, METAANALYSIS, Science & Technology, CRYPTOGENIC STROKE, business.industry, Warfarin, medicine.disease, EFFICACY, ATRIAL-FIBRILLATION, Human medicine, business, Brain Ischemia/prevention & control, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

WOS: 000434263000007, PubMed: 29766772, BACKGROUND Embolic strokes of undetermined source represent 20% of ischemic strokes and are associated with a high rate of recurrence. Anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, may result in a lower risk of recurrent stroke than aspirin. METHODS We compared the efficacy and safety of rivaroxaban (at a daily dose of 15 mg) with aspirin (at a daily dose of 100 mg) for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism but without arterial stenosis, lacune, or an identified cardioembolic source. The primary efficacy outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis; the primary safety outcome was the rate of major bleeding. RESULTS A total of 7213 participants were enrolled at 459 sites; 3609 patients were randomly assigned to receive rivaroxaban and 3604 to receive aspirin. Patients had been followed for a median of 11 months when the trial was terminated early because of a lack of benefit with regard to stroke risk and because of bleeding associated with rivaroxaban. The primary efficacy outcome occurred in 172 patients in the rivaroxaban group (annualized rate, 5.1%) and in 160 in the aspirin group (annualized rate, 4.8%) (hazard ratio, 1.07; 95% confidence interval [CI], 0.87 to 1.33; P=0.52). Recurrent ischemic stroke occurred in 158 patients in the rivaroxaban group (annualized rate, 4.7%) and in 156 in the aspirin group (annualized rate, 4.7%). Major bleeding occurred in 62 patients in the rivaroxaban group (annualized rate, 1.8%) and in 23 in the aspirin group (annualized rate, 0.7%) (hazard ratio, 2.72; 95% CI, 1.68 to 4.39; P, BayerBayer AG; Janssen Research and Development, Supported by Bayer and Janssen Research and Development.

Published
2018

38. Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial

Author

Kasner, S. E., Swaminathan, B., Lavados, P., Sharma, M., Muir, K., Veltkamp, R., Ameriso, S. F., Endres, M., Lutsep, H., Messe, S. R., Spence, J. D., Nedeltechev, K., Perera, K., Santo, G., Olavarria, V., Lindgren, A., Bangdiwala, S., Shoamanesh, A., Berkowitz, S. D., Mundl, H., Connolly, S. J., Hart, R. G., Abdelhamid, N., Abdul Rahman, D., Abdul-Saheb, M., Abreu, P., Abroskina, M., Abu Ahmad, F., Accassat, S., Acciaresi, M., Adami, A., Ahmad, N., Ahmed, F., Alberto Hawkes, M., Alemseged, F., Ali, A., Altavilla, R., Alwis, L., Amarenco, P., Amaro, S., Amaya Sanchez, L. E., Amelia Pinto, A., Amin, H., Amino, T., Amjad, A. K., Anagnostou, E., Andersen, G., Anderson, C., Anderson, D. C., Andrea Falco, M., Andres Mackinnon, F., Andreu, D., Androulakis, M., Angel Gamero, M., Angel Saredo, G., Angeles Diaz, R., Angels Font, M., Anticoli, S., Arauz, A., Arauz Gongora, A. A., Araya, P., Arenillas Lara, J. F., Arias Rivas, S., Arnold, M., Augustin, S., Avelar, W., Azevedo, E., Babikian, V., Bacellar, A., Badalyan, K., Bae, H. J., Baez Martinez, E. M., Bagelmann, H., Bailey, P., Bak, Z., Baker, M., Balazs, A., Baldaranov, D., Balogun, I., Balueva, T., Bankuti, Z., Bar, M., Baranowska, A., Bardutzky, J., Barker Trejo, S., Barlinn, J., Baronnet, F., Barroso, C., Barteys, M., Bartolottiova, T., Barulin, A., Bas, M., Bashir, S., Basile, V., Bathe-Peters, R., Bathula, R., Batista, C., Batur Caglayan, H., Baumgartner, P., Bazan, R., Bazhenova, O., Beaudry, M., Beer, J., Behnam, Y., Beilei, C., Beinlich, A., Bejot, Y., Belkin, A., Benavente, O. R., Benjamin, A., Berardi, V., Bereczki, D., Berlingieri, J., Berrios, W., Berrouschot, J., Bhandari, M., Bhargavah, M., Bicker, H., Bicsak, T., Bilik, M., Bindila, D., Birchenall, J., Birnbaum, L., Black, T., Blacker, D., Blacquiere, D., Blanc-Labarre, C., Blank, C., Blazejewska-Hyzorek, B., Bloch, S., Bodiguel, E., Bogdanov, E., Boos, L., Borcsik, L., Bornstein, N., Bouly, S., Braga, G., Bragado, I., Bravi, M. C., Brokalaki, C., Brola, W., Brouns, R., Bruce, D., Brzoska-Mizgalska, J., Buck, B., Buksinska-Lisik, M., Burke, J., Burn, M., Bustamante, G., Cabrejo, L., Cai, K., Cajaraville, S., Calejo, M., Calvet, D., Campillo, J., Campos Costa, E., Camps, P., Can Alaydin, H., Candeloro, E., Canepa, C., Cantu Brito, C. G., Cappellari, M., Carcel, C., Cardona Portela, P., Cardoso, F., Carek, M., Carletti, M., Carlos Portilla, J., Caruso, P., Casado-Naranjo, I., Castellini, P., Castro, D., Castro Meira, F., Cavallini, A., Cayuela Caudevilla, N., Cenciarelli, S., Cereda, C., Cerrone, P., Chakrabarti, A., Chaloulos-Iakovidis, P., Chamorro, A., Chandrasena, D., Chang, D. I., Che, C., Chembala, J., Chen, J., Chen, Z., Chen, T., Chen, H., Chen, X., Chen, G., Chen, L., Chen, S., Cheripelli, B., Chin, M., Chiquete Anaya, E., Chorazy, M., Christensen, H., Christensen, T., Christian, L., Chu, F., Chung, C. S., Clark, W., Clarke, R., Claverie, S., Clemente Agostoni, E., Clissold, B., Coelho, J., Cohen, D., Colakoglu, S., Collas, D., Condurso, R., Consoli, D., Constantin, C., Constantino Silva, A. 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R., Benjamin, A., Berardi, V., Bereczki, D., Berlingieri, J., Berrios, W., Berrouschot, J., Bhandari, M., Bhargavah, M., Bicker, H., Bicsak, T., Bilik, M., Bindila, D., Birchenall, J., Birnbaum, L., Black, T., Blacker, D., Blacquiere, D., Blanc-Labarre, C., Blank, C., Blazejewska-Hyzorek, B., Bloch, S., Bodiguel, E., Bogdanov, E., Boos, L., Borcsik, L., Bornstein, N., Bouly, S., Braga, G., Bragado, I., Bravi, M. C., Brokalaki, C., Brola, W., Brouns, R., Bruce, D., Brzoska-Mizgalska, J., Buck, B., Buksinska-Lisik, M., Burke, J., Burn, M., Bustamante, G., Cabrejo, L., Cai, K., Cajaraville, S., Calejo, M., Calvet, D., Campillo, J., Campos Costa, E., Camps, P., Can Alaydin, H., Candeloro, E., Canepa, C., Cantu Brito, C. G., Cappellari, M., Carcel, C., Cardona Portela, P., Cardoso, F., Carek, M., Carletti, M., Carlos Portilla, J., Caruso, P., Casado-Naranjo, I., Castellini, P., Castro, D., Castro Meira, F., Cavallini, A., Cayuela Caudevilla, N., Cenciarelli, S., Cereda, C., Cerrone, P., Chakrabarti, A., Chaloulos-Iakovidis, P., Chamorro, A., Chandrasena, D., Chang, D. I., Che, C., Chembala, J., Chen, J., Chen, Z., Chen, T., Chen, H., Chen, X., Chen, G., Chen, L., Chen, S., Cheripelli, B., Chin, M., Chiquete Anaya, E., Chorazy, M., Christensen, H., Christensen, T., Christian, L., Chu, F., Chung, C. S., Clark, W., Clarke, R., Claverie, S., Clemente Agostoni, E., Clissold, B., Coelho, J., Cohen, D., Colakoglu, S., Collas, D., Condurso, R., Consoli, D., Constantin, C., Constantino Silva, A. B., Contardo, L., Corlobe, A., Correia, M., Correia, C., Cortijo Garcia, E., Coull, B., Coutts, S., Coveney, S., Cras, P., Crols, R., Crozier, S., Csanyi, A., Csiba, L., Csontos, K., Csuha, R., Cui, L., Cunha, L., Curtze, S., Czerska, M., Czlonkowska, A., Czurko, M., Czuryszkiewicz, M., Dagnino, M., Dai, C., Daineko, A., Dalek, G., Damgaard, D., Danese, A., Dani, K., Danku, V., Dario Toledo, W., Davalos, A., De Havenon, A., De Keyser, J., De Klippel, N., De La Torre, J., De Pauw, A., De Smedt, A., De Torres, R., De Vries Basson, M. M., Dearborn, J., Deganutto, R., Degeorgia, M., Deguchi, I., Del Giudice, A., Delcourt, C., Delgado-Mederos, R., Della Marca, Giacomo, Delpont, B., Deltour, S., Demets, D. L., Dennis, M., Desai, J., Devine, J., Dhollander, I., Di Mascio, M. T., Diaconu, M., Diaz Otero, F., Dietzel, J., Diez-Tejedor, E., Ding, N., Ding, J., Diomedi, M., Dioszeghy, P., Distefano, M., Domigo, V., Dorodnicov, E., Dossi, D., Doubal, F., Druzenko, I., Du, P., Du, J., Duman, T., Duodu, Y., Dutta, D., Dylewicz, L., Eckstein, J., Ehrensperger, E., Ehrlich, S., Einer Allende, G., Elena Halac, B., Elyas, S., Engelbrecht, J. M., Engelter, S., Epinat, M., Eren, F., Esbjornsson, M., Escribano, B., Escudero, I., Esisi, B., Essa, B., Esterbauer, M., Evans, N., Eveson, D., Fabio, S., Fang, L., Fanta, S., Fares, M., Fatar, M., Faust, K., Favate, A., Fazekas, F., Federica Denaro, M., Fedin, A., Felipe Amaya, P., Feng, J., Ferencova, K., Fernanda Gilli, M., Fernandez, M. D., Fernandez Pirrone, P. 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S., Heine, M., Held, V., Hellwig, S., Henkner, J., Henninger, N., Hermans, S., Hernandez, J., Herrero, D., Hervieu-Begue, M., Herzig, R., Hicken, L., Hieber, M., Hill, M., Hirose, M., Hobeanu, M. C., Hobson, B., Hochstetter, M., Hoe Heo, J., Hoffmann, M., Holmstedt, C., Hon, P., Hong, K. S., Honma, Y., Horev, A., Horgan, G., Horvath, L., Horvath, M., Hoyer, C., Huang, D., Huang, H., Huber, B., Huhtakangas, J., Hussain, M., Igarashi, S., Iglesias Mohedano, A. M., Ignacio Tembl, J., Impellizzeri, M., Inanc, Y., Ioli, P., Irina Aniculaesei, A., Ishida, K., Itabashi, R., Iversen, H., Jagolino, A., Jakab, K., Jander, S., Janka, H., Jankovych, J., Jansen, J., Jasek, L., Javier Alet, M., Javor, L., Jin, X., Jing, P., Joachim, B., Joan Macleod, M., Johnson, M., Jose Martin, J., Joyner, C., Judit Szabo, K., Jun-Oconnell, A., Jura, R., Kaczorowska, B., Kadlcikova, J., Kahles, T., Kakaletsis, N., Kakuk, I., Kalinowska, K., Kaminska, K., Kaneko, C., Kanellos, I., Kapeller, P., Kapica-Topczewska, K., Karasz, O., Karlinski, M., Karlsson, J. E., Kasa, K., Kashaeva, E., Kaste, M., Kasza, J., Katalin Iljicsov, A., Katsurayama, M., Kaur, S., Kawanishi, M., Kaygorodtseva, S., Ke, K., Kei, A., Keilitz, J., Kellner, J., Kelly, P., Kelly, S., Kemlink, D., Kerekgyarto, M., Keskinarkaus, I., Khairutdinova, D., Khanna, A., Khaw, A., Kholopov, M., Khoumri, C., Kirpicheva, S., Kirshner, H., Kitagawa, K., Kittner, S., Kivioja, R., Klein, F., Kleindorfer, D., Kleinig, T., Klivenyi, P., Knecht, S., Kobayashi, Y., Kobayashi, A., Koch, M., Koehler, L., Koivu, M., Kolianov, V., Koltsov, I., Kondo, T., Konkov, I., Kopecky, S., Korompoki, E., Korpela, J., Kosarz-Lanczek, K., Koutroubi, A., Kovacs, K., Kovacs, T., Kovacs, H., Kowalczyk, K., Kowalska, M., Krajickova, D., Kral, M., Krarup Hansen, C., Kraska, J., Krebs, S., Krejci, V., Kremer, C., Kreuzpointer, R., Krzyzanowska, M., Kucken, D., Kulakowska, A., Kunzmann, J., Kurenkova, N., Kuris, A., Kurkowska-Jastrzebska, I., Kurtenkova, N., Kurushina, O., Kusnick, G., Kustova, M., Kuwashiro, T., Kwan Cha, J., Lago, A., Lagutenko, M., Lajos, B., Lambeck, J., Lamy, C., Landolfi, A., Lanfranconi, S., Lang, W., Lara Lezama, L. B., Lara Rodriguez, B., Largo, T., Lasek-Bal, A., Latte, L., Lauer, V., Le Bouc, R., Leal Cantu, R., Lechner, H., Lecouturier, K., Leder, S., Lee, J., Lee, B. C., Leger, A., Leira, E., Leisse, I., Leker, R., Lembo, G., Lenskaya, L., Leyden, J., Li, G., Li, M., Li, S., Li, J., Liamis, G., Liang, H., Liang, Z., Ligot, N., Lin, H., Lindert, R., Linna, M., Litwin, T., Liu, K., Liu, X., Llull, L., Lohninger, B., Longoni, M., Loomis, C., Lopes, D., Lopez Fernandez, M., Lopez Garza, N., Lord, A., Louw, S., Lovasz, R., Lowenkopf, T., Lu, Z., Lubke-Detring, S. C., Luder, R., Lujan, S., Luo, B., Lupinogina, L., Luschin, G., Lvova, A., Ly, J., Grosse, G. M., Ma, H., Ma, C., Machado, M., Machado, C., Macher, S., Machetanz, J., Macian-Montoro, F., Mackey, E., Mackey, A., Maclean, G., Maestre-Moreno, J., Magadan, A., Magyar, T., Mahagney, A., Majid, A., Majjhoo, A., Makaritsis, K., Mandzia, J., Mangas Guijarro, M., Mangion, D., Manios, E., Mann, S., Manning, L., Manno, C., Manuel Garcia, J., Maqueda, V., Mar Castellanos, M., Mar Freijo, M., Marando, C., Marcela Lepera, S., Marcos Couto, J., Maria Bruera, G., Maria Greco, L., Maria Lorenzo, A., Maria Obmann, S., Maria Roa, A., Marini, C., Marinkovic, I., Mario Sumay, G., Mario Torres, C., Marko, M., Markova, S., Markus, H., Marsh, R., Marsili, E., Marta Esnaola, M., Marta Moreno, J., Marti-Fabregas, J., Martina Angelocola, S., Martinez Sanchez, P., Martinez-Majander, N., Martins, S., Marzelik, O., Mastrocola, S., Matamala, G., Matoltsy, A., Matosevic, B., Matsumoto, S., Maud, A., Mauri Cabdevila, G., May, Z., Mayasi, Y., Mayr, A., Mazzoli, T., Mcarthur, K., Mccullough, L., Medina Pech, C. 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W., Munoz, S., Murphy, C., Murphy, S., Murtuzova, A., Musuka, T., Mutzenbach, J., Myint, M., Mysliwy, W., Naccarato, M., Naeije, G., Nagakane, Y., Natarajan, I., Navaratnam, D., Nave, A., Nazliel, B., Nedeltchev, K., Nel, J., Nell, H., Nemeth, R., Nemeth, L., Neto, O., Ng, K., Ngeh, J., Nicolas Chialvo, L., Nieminen, T., Nikkanen, M., Nikl, J., Nikoforova, M., Nishino, S., Nishiyama, Y., Njovane, X., Nogawa, S., Nombela, F., Norrving, B., Nosek, K., Nowak, B., Nowakowska-Sledz, E., Ntaios, G., Numminen, H., Nunez, F., Obadia, M., Oberndorfer, S., Obrezan, A., Ochiai, J., Oczkowski, W., O'Donnell, M. 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F., Penn, A., Pentek, S., Pepper, E., Pereira, L., Perez, Y., Perez, S., Perez Leguizamon, P., Pernicka, M., Perry, R., Persico, A., Pesant, Y., Peska, S., Peters, D., Peters, G., Pettigrew, L., Phan, T., Philippi, S., Phinney, T., Pico, F., Pidal, A., Piechowski-Jozwiak, B., Pieroni, A., Pineiro, S., Piras, V., Pizova, N., Polanco, J., Polin, M., Polyakov, A., Polychronopoulou, E., Polymeris, A., Popov, D., Poppe, A., Postorino, P., Pozzerese, C., Pradhan, M., Prats, L., Prazdnichkova, E., Prendl, B., Pretorius, M., Profice, P., Prokopenko, S., Pudov, E., Pujol Lereis, V., Punzo Bravo, G., Purroy, F., Qiu, J., Qu, X., Quenardelle, V., Quesada Garcia, H., Radrizzani, L., Radtke, A., Raffelsberger, T., Ramirez Moreno, J. M., Ramos-Estebanez, C., Rani, A., Rapantova, P., Rashed, K., Rasheed Nihara, A., Rasmussen, J., Redondo Robles, L., Reif, M., Reiner, P., Rekova, P., Renu, A., Repetto, M., Reyes, P., Reyes Morales, S., Rha, J. H., Ribeiro, J., Ricci, S., Richard, C., Rigual, R., Rinaldi, C., Riveira Rodriguez, C., Rizzato, B., Robinson, T. G., Rocco, A., Rodrigues, M., Rodriguez, G., Rodriguez Campello, A., Rodriguez Lucci, F., Rodriguez Yanez, M., Roesler, C., Roffe, C., Roine, R., Roine, S., Roldan, A., Romana Pezzella, F., Romano, M., Roos, J. S., Rosso, C., Rostrup Kruuse, C., Roth, Y., Roukens, R., Roveri, L., Rozanski, D., Rozniecki, J., Rozsa, C., Rudilosso, S., Ruiz Ares, G., Ruiz Franco, A., Rum, G., Ruuskanen, J., Rybinnik, I., Ryota, K., Saarinen, J., Saavedra, V., Sabben, C., Sabet, A., Sagris, D., Sahlas, J., Sakai, N., Salamanca, P., Salgado, P., Salig, S., Salletmayr, T., Salnikov, M., Samoshkina, O., Samson, Y., Sanak, D., Sanchez Ceron, M., Santalucia, P., Santamaria Cadavid, M., Santiago, P., Sanz Cuesta, B., Sargento, J., Sarraj, A., Sas, K., Sas, A., Satoshi, O., Satsoglou, S., Sattar, N., Savitz, S., Savopoulos, C., Saw, J., Sawicka, M., Sawyer, R., Scandura, T., Schillinger, N., Schindler, J., Schlachetzki, F., Schneider, I., Schuppner, R., Schurig, J., Schwarzbach, C. 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I., Soldatov, M., Solganov, I., Soloveva, L., Solovyeva, E., Sonntag, N., Soors, P., Sorgun, M., Soriano, C., Spence, D., Spengos, K., Sposato, L., Staaf, G., Stadler, K., Stakhovskaya, L., Stamatelopoulos, K., Steinert, S., Stetkarova, I., Stiehm, M., Stocker, R., Stoinski, J., Stoll, A., Stotts, G., Stumpp, A., Sucapane, P., Suenaga, T., Sun, X., Sundararajan, S., Sung Kim, J., Suzuki, H., Svaneborg, N., Szasz, G., Szczuchniak, W., Szczyrba, S., Szegedi, N., Szekely, A., Szewczyk, Z., Szilagyi, G., Szlufik, S., Szoboszlai, K., Szpisjak, L., Sztajzel, R., Sztriha, L., Ta Wil, S. E., Taggeselle, J., Takamatsu, K., Takao, M., Taki, W., Takizawa, S., Talahma, M., Tamayo, A., Tan, J., Tanne, D., Tapanainen, A., Tapiola, T., Tarasiuk, J., Tatlisumak, T., Tayal, A., Tcvetkova, S., Teal, P., Tejada Garcia, J., Tejada Meza, H., Tenora, D., Terceno, M., Terentiou, A., Tezcan, S., Thaler, D., Thomson, A., Thouvenot, E., Tiainen, M., Timberg, I., Timsit, S., Tinchon, A., Tirschwell, D., Togay Isikay, C., Tokunaga, K., Tolino, M., Toloza, C., Tomelleri, G., Tomoyuki, K., Tomppo, L. M., Tong, Z., Tong, L., Toni, D., Torres, J., Tossavainen, C., Toth, G., Tountopoulou, A., Touze, E., Tovar, M., Toyoda, K., Trillo, S., Trommer, A., Tropepi, D., Tryambake, D., Tu, H., Tuetuencue, S., Tumova, R., Tumpula, O., Turc, G., Tutaj, A., Tynkkynen, J., Uchiyama, S., Uchwat, U., Uhrinyakova, L., Ulku Acar, R., Uluduz Ugurlu, D., Urra, X., Urui, S., Usero Ruiz, M., Vaclavik, D., Vahedi, K., Valikovics, A., Valpas, J., Van Acker, P., Van Daele, W., Vanderschueren, G., Vanina Jure, L., Varela, R., Varga, Z., Varvat, J., Varvyanskaya, N., Vasco Salgado, A., Vasko, P., Vass, L., Vassilopoulou, S., Vastagh, I., Vazquez, P., Vecsei, L., Venti, M., Verdugo, M., Verocai, V., Veronica Marroquin, M., Veronica Simonsini, C., Veverka, T., Vigl, M., Vila, A., Vilar, C., Villanueva Osorio, J. A., Virta, J., Vitkova, E., Voglsperger, B., Volna, J., Von Weitzel-Mudersbach, P. A., Vora, N., Voznyuk, I., Wach-Klink, A., Wacongne, A., Walters, D., Wang, Y., Wang, J., Wang, L., Wang, X., Wang, W., Wang, N., Wang, D., Wang, H., Warnack, W., Wartenberg, K., Waters, R., Waters, M., Webb, T., Weber, J., Weiss, G., Weissenborn, K., Weitz, J. I., Weller, B., Wen, G., Weng, G., Werner, P., Werring, D., Wester, P., Whiteley, W., Whiting, R., Wijeratne, T., Willems, C., Wilson, L., Wilson, C., Winder, T., Windt, J., Winkler, A., Winska-Tereszkiewicz, A., Wisniewska, A., Wittayer, M., Wlodek, A., Wojnarowska-Arendt, A., Wolf, M., Wolff, V., Wolter, C., Wong, A., Wook Nah, H., Worthmann, H., Wu, W., Wu, S., Wunderlich, S., Wurzinger, H., Wyse, D. G., Xiao, B., Xiaopeng, W., Ximenez-Carrillo, A., Xiong, L., Xiong, Y., Xiong, W., Xu, Y., Xu, J., Xu, Z., Yalo, B., Yamada, T., Yamasaki, M., Yang, L., Yang, Y., Yang, X., Yang, Q., Yang, B., Yang, J., Yasuhiro, I., Yee Lam, M., Yegappan, C., Yip, S., Ylikallio, E., Ylikotila, P., Yongwon Jin, A., Yoon, B. W., Yoshida, Y., Yperzeele, L., Yuan, H., Yuasa, H., Zalewska, J., Zanferrari, C., Zapata, E., Zboznovits, D., Zelenka, I., Zhang, C., Zhang, B., Zhang, S., Zhang, M., Zhang, X., Zhang, J., Zhao, L., Zhirnova, O., Zhou, L., Zielinska-Turek, J., Zinchenko, I., Ziomek, M., Zitzmann, A., Zweifler, R., Zwiernik, J., and Della Marca G. (ORCID:0000-0001-6914-799X)

Abstract

Background: Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial. Methods: NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS. For this prespecified subgroup analysis, cohorts with and without PFO were defined on the basis of transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE). The primary efficacy outcome was time to recurrent ischaemic stroke between treatment groups. The primary safety outcome was major bleeding, according to the criteria of the International Society of Thrombosis and Haemostasis. The primary analyses were based on the intention-to-treat population. Additionally, we did a systematic review and random-effects meta-analysis of studies in which patients with cryptogenic stroke and PFO were randomly assigned to receive anticoagulant or antiplatelet therapy. Findings: Between Dec 23, 2014, and Sept 20, 2017, 7213 participants were enrolled and assigned to receive rivaroxaban (n=3609) or aspirin (n=3604). Patients were followed up for a mean of 11 months because of early trial termination. PFO was reported as present in 534 (7·4%) patients on the basis of either TTE or TOE. Patients with PFO assigned to receive aspirin had a recurrent ischaemic stroke rate of 4·8 events per 100 person-years compared with 2·6 events per 100 person-years in those treated with rivaroxaban. Among patients with known PFO, there was insufficient evidence to support a difference in risk o

Published
2018

40. Sudden Arrhythmic Death During Exercise: A Post-Mortem Genetic Analysis

Author

Campuzano O, Sanchez-Molero O, Fernández A, Mademont-Soler I, Coll M, Perez-Serra A, Mates J, Del Olmo B, Pico F, Nogue-Navarro L, Sarquella-Brugada G, Iglesias A, Cesar S, Esther Carro Fernandez, Borondo JC, Brugada-Terradellas J, Castellà J, Medallo J, and Brugada R

Subjects
Rare Variant, Human Gene Mutation Database, Catecholaminergic Polymorphic Ventricular Tachycardia, Sudden Cardiac Death, Brugada Syndrome
Abstract

BACKGROUND: Sudden cardiac death is a natural and unexpected death that occurs within 1 h of the first symptom. Most sudden cardiac deaths occur during exercise, mostly as a result of myocardial infarction. After autopsy, some cases, especially in the young, are diagnosed as cardiomyopathies or remain without a conclusive cause of death. In both situations, genetic alterations may explain the arrhythmia. OBJECTIVE: Our aim was to identify a genetic predisposition to sudden cardiac death in a cohort of post-mortem cases of individuals who died during exercise, with a structurally normal heart, and were classified as arrhythmogenic death. METHODS: We analyzed a cohort of 52 post-mortem samples from individuals

Published
2017

41. Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's

Author

Liu, Ganqiang, Boot, Brendon, Cormier-Dequaire, Florence, Corvol, Jean-Christophe, Barker, Roger A, Heutink, Peter, Marinus, Johan, Williams-Gray, Caroline H, Scherzer, Clemens R, Progression, International Genetics of Parkinson Disease, Scherzer, C., Hyman, B. T., Locascio, Joseph J, Ivinson, A. J., Trisini-Lipsanopoulos, A., Franco, D., Burke, K., Sudarsky, L. R., Hayes, M. T., Umeh, C. C., Growdon, J. H., Schwarzschild, M. A., Hung, A. Y., Jansen, Iris E, Flaherty, A. W., Wills, A-M, Mejia, N. I., Gomperts, S. N., Khurana, V., Selkoe, D. J., Yi, T., Page, K., Liao, Z., Barker, R., Winder-Rhodes, Sophie, Foltynie, T., Williams-Gray, C. H., Mason, S., Winder-Rhodes, S., Breen, D., Cummins, G., Evans, J., Eberly, Shirley, Corvol, J-C, Brice, A., Elbaz, A., Mallet, A., Vidailhet, M., Bonnet, A-M, Bonnet, C., Grabli, D., Hartmann, A., Klebe, S., Elbaz, Alexis, Lacomblez, L., Mangone, G., Bourdain, F., Brandel, J-P, Derkinderen, P., Durif, F., Mesnage, V., Pico, F., Rascol, O., Forlani, S., Brice, Alexis, Lesage, S., Tahiri, K., van Hilten, J. J., Marinus, J., Duong, K., Ravina, Bernard, Dong, X., Hutten, S. J., Amr, S. S., Shoulson, I., Tanner, C. M., Lang, A. E., Nalls, M. A., van Hilten, Jacobus J, Human genetics, Amsterdam Neuroscience - Neurodegeneration, Neuro-Psycho Pharmacologie des Systèmes Dopimanégiques sous-corticaux (NPsy-Sydo), CHU Clermont-Ferrand-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Neurologie et thérapeutique expérimentale, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hertie Institute for Clinical Brain Research [Tubingen], University of Tübingen, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, 0301 basic medicine, Oncology, medicine.medical_specialty, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Disease, medicine.disease_cause, genetics [Glucosylceramidase], etiology [Cognitive Dysfunction], 03 medical and health sciences, 0302 clinical medicine, Parkinson Disease/complications, genetics [Parkinson Disease], Internal medicine, Genetic variation, medicine, Humans, Cognitive Dysfunction/etiology, ddc:610, Longitudinal Studies, Cognitive decline, Allele, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Genetics, genetics [Gaucher Disease], Mutation, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Proportional hazards model, [SCCO.NEUR]Cognitive science/Neuroscience, Hazard ratio, genetics [Cognitive Dysfunction], [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, Middle Aged, Confidence interval, 3. Good health, 030104 developmental biology, Neurology, Glucosylceramidase/genetics, Disease Progression, Glucosylceramidase, Female, Neurology (clinical), complications [Gaucher Disease], complications [Parkinson Disease], Gaucher Disease/complications, Psychology, 030217 neurology & neurosurgery
Abstract

OBJECTIVE: We hypothesized that specific mutations in the β-glucocerebrosidase gene (GBA) causing neuropathic Gaucher's disease (GD) in homozygotes lead to aggressive cognitive decline in heterozygous Parkinson's disease (PD) patients, whereas non-neuropathic GD mutations confer intermediate progression rates.METHODS: A total of 2,304 patients with PD and 20,868 longitudinal visits for up to 12.8 years (median, 4.1) from seven cohorts were analyzed. Differential effects of four types of genetic variation in GBA on longitudinal cognitive decline were evaluated using mixed random and fixed effects and Cox proportional hazards models.RESULTS: Overall, 10.3% of patients with PD and GBA sequencing carried a mutation. Carriers of neuropathic GD mutations (1.4% of patients) had hazard ratios (HRs) for global cognitive impairment of 3.17 (95% confidence interval [CI], 1.60-6.25) and a hastened decline in Mini-Mental State Exam scores compared to noncarriers (p = 0.0009). Carriers of complex GBA alleles (0.7%) had an HR of 3.22 (95% CI, 1.18-8.73; p = 0.022). By contrast, the common, non-neuropathic N370S mutation (1.5% of patients; HR, 1.96; 95% CI, 0.92-4.18) or nonpathogenic risk variants (6.6% of patients; HR, 1.36; 95% CI, 0.89-2.05) did not reach significance.INTERPRETATION: Mutations in the GBA gene pathogenic for neuropathic GD and complex alleles shift longitudinal cognitive decline in PD into "high gear." These findings suggest a relationship between specific types of GBA mutations and aggressive cognitive decline and have direct implications for improving the design of clinical trials. Ann Neurol 2016;80:674-685.

Published
2016

42. EFFICIENCY AND PRODUCTIVITY IN VENEZUELAN INDUSTRY DIRECT REDUCTION IRON IN GUAYANA REGION

Author

Jairo J. Pico F. and Hugo R. Martínez C.

Subjects
Productividad, Análisis Envolvente de Datos (DEA-Rusell), Producción Hierro Reducción Directa, Eficiencia técnica, lcsh:Business, Índice Malmquist Hicks-Moorsteen, lcsh:HF5001-6182
Abstract

The overall objective of the research was to analyze the efficiency and productivity in the industry Venezuelan Direct Reduced Iron (DRI) in the Guayana region during 2005 to 2009. The methodology used was Data Envelopment Analysis DEA-Malmquist Index and Russell Hicks-Moorsteen. The results indicate an efficiency of 98% input and a waste of the installed capacity in the industry of 48%. It also reduces the overall productivity of 80.8% on average, and 2009-2011, there is a tendency to lower it, reaching a value of 60%

Published
2013

43. EVALUACIÓN DE LA COMPOSICIÓN NUTRICIONAL, ANTINUTRICIONAL Y BIODISPONIBILIDAD IN VITRO DE DIFERENTES EXTRACTOS FOLIARES

Author

Teresa Sanchez, Paola Imbachí N, Darwin Ortiz, Helena Pachón, Sayda Milena Pico F, Andrés Escobar S, Ingrid Aragón G, and Dayron Gutiérrez

Subjects
componentes antinutricionales, concentrado de hoja, Nutrition and Dietetics, biodisponibilidad in vitro, Chemistry, componentes nutricionales, Composition (visual arts), Food science, Extracto foliar, In vitro, Food Science, Bioavailability
Abstract

Los extractos foliares (EF) son utilizados como complemento nutricional en países como Nicaragua y Tanzania. Se evaluaron hojas y EF de yuca, fríjol, batata y alfalfa, y se cuantificó los componentes nutricionales, antinutricionales y biodisponibilidad por métodos in vitro. En promedio (DE), el EF de fríjol tiene una elevada concentración de hierro (1006,23 (8,49) mg/kg); el EF de yuca tiene alta concentración de zinc (110,65 (6,72) mg/ kg) y proteína soluble (34,23 (3,81) g/kg). Así mismo, la digestibilidad in vitro de proteína en los EFs de yuca, fríjol y alfalfa fueron superiores a 71,18%; hierro dializable in vitro menor a 2,29%; la relación molar fitato:zinc inferior a 0,08 y la bioaccesibilidad all-trans-β -caroteno superior a 23,85%. Estos valores sugieren una alta asimilación de proteína, zinc y all-trans-β -caroteno, y una baja asimilabilidad de hierro. Los EFs pueden ser una alternativa nutricional en la alimentación en países que carecen de diversificación alimentaria.

Published
2011

44. Estimated GFR and the Effect of Intensive Blood Pressure Lowering after Acute Intracerebral Hemorrhage.

Author

Fischer R., Gama G., Fonseca L., Moreira G., Veloso L.M., Pinheiro D., Paredes L., Rozeira C., Gregorio T., Segura Martin T., Ayo O., Garcia-Garcia J., Feria Vilar I., Gomez Fernandez I., Amaro S., Urra X., Obach V., Cervera A., Silva Y., Serena J., Castellanos M., Terceno M., Van Eendenburg C., Weck A., Findling O., Ludi R., Warburton E.A., Day D., Butler N., Bumanlag E., Caine S., Steele A., Osborn M., Dodd E., Murphy P., Esisi B., Brown E., Hayman R., Baliga V.K.V., Minphone M., Kennedy J., Reckless I., Pope G., Teal R., Michael K., Manawadu D., Kalra L., Lewis R., Mistry B., Cattermole E., Hassan A., Mandizvidza L., Bamford J., Brooks H., Bedford C., Whiting R., Baines P., Hussain M., Harvey M., Fotherby K., McBride S., Bourke P., Morgan D., Jennings-Preece K., Price C., Huntley S., Riddell V.E., Storey G., Lakey R.L., Subramanian G., Jenkinson D., Kwan J., David O., Tiwari D., James M., Keenan S., Eastwood H., Shaw L., Kaye P., Button D., Madigan B., Williamson D., Dixit A., Davis J., Hossain M.O., Ford G.A., Parry-Jones A., O'Loughlin V., Jarapa R., Naing Z., Lovelock C., O'Reilly J., Khan U., Bhalla A., Rudd A., Birns J., Werring D.J., Law R., Perry R., Jones I., Erande R., Roffe C., Natarajan I., Ahmad N., Finney K., Lucas J., Mistri A., Eveson D., Marsh R., Haunton V., Fugate J.E., Lepore S.W., Zheng D., Sato S., Arima H., Heeley E., Delcourt C., Cao Y., Chalmers J., Anderson C.S., Davis S., Huang Y., Lavados P., Neal B., Parsons M.W., Lindley R., Morgenstern L., Robinson T., Stapf C., Tzourio C., Wang J.G., Chen S., Chen X.Y., Cui L., Liu Z., Lu C., Wang J., Wu S., Xu E., Yang Q., Zhang C., Zhang J., Beer R., Schmutzhard E., Redondo P., Kaste M., Soinne L., Tatlisumak T., Wartenberg K., Ricci S., Klijn K., Azevedo E., Chamorro A., Arnold M., Fischer U., Kaul S., Pandian J., Boyini H., Singh S., Rabinstein A.A., Estol C., Silva G., Olavarria V.V., Robinson T.G., Simes R.J., Bousser M.-G., Hankey G., Jamrozik K., Johnston S.C., Li S., Bailey K., Cheung T., Chintapatla S., Ducasse E., Erho T., Hata J., Holder B., Knight E., Leroux M., Sasse T., Odgers E., Walsh R., Wolfowicz Z., Chen G., Fuentes S., Peng B., Schneble H.-M., Wang M.-X., Billot L., Heritier S., Li Q., Woodward M., Abimbola S., Anderson S., Chan E., Cheng G., Chmielnik P., Leighton S., Liu J.-Y., Rasmussen B., Saxena A., Tripathy S., Armenis M., Baig M.A., Naidu B., Starzec G., Steley S., Moles A., Ruiz A., Zimmermann M., Marinho J., Alves S., Angelim R., Araujo J., Kawakami L., Bustos C., Gonzalez F., Munoz Venturelli P., Chen X., Jia R., Li N., Qu S., Shu Y., Song A., Sun J., Xiao J., Zhao Y., Huang Q., Vicaut E., Chamam A., Viaud M.-C., Dert C., Fiedler U., Jovis V., Kabla S., Marchand S., Pena A., Mallikarjuna K., Hasan N., Berge E., Sandset E.C., Forarsveen A.S., Richardson D., Kumar T., Lewin S., Poulter N., Field J., Anjum A., Wilson A., Perelmuter H., Agarie A.M., Barboza A.G., Recchia L.A., Miranda I.F., Rauek S.G., Duplessis R.J., Dewey H., Walker L., Petrolo S., Bladin C., Sturm J., Crimmins D., Griffiths D., Schutz A., Zenteno V., Miteff F., Spratt N., Kerr E., Levi C.R., Phan T.G., Ma H., Sanders L., Moran C., Wong K., Read S., Henderson R., Wong A., Hull R., Skinner G., Hand P., Yan B., Tu H., Campbell B., Blacker D.J., Wijeratne T., Pathirage M., Jasinararchchi M., Matkovic Z., Celestino S., Gruber F., Vosko M.R., Diabl E., Rathmaier S., Pfausler B., Helbok R., Fazekas F., Poltrum B., Zechner B., Trummer U., Rutgers M.P., Peeters A., Dusart A., Duray M.-C., Parmentier C., Ferrao-Santos S., Brouns R., De Raedt S., De Smedt A., Vanhooff R.-J., De Keyser J., Martins S.C.O., De Almeida A.G., Broudani R., Titton N.F., De Freitas G.R., Cardoso F.M., Giesel L.M., Lima N.A., Ferraz De Almeida A.C., Gomes R.B., Borges Dos Santos T.S., Veloso Soares E.M., Neto O.L.A., Silva G.S., Gomes D.L., De Carvalho F.A., Miranda M., Marques A., Zetola V.F., De Matia G., Lange M.C., Montes J., Reccius A., Soto A., Rivas R., Klapp C., Illanes S., Aguilera C., Castro A., Figueroa C., Benavides J., Salamanca P., Concha M.C., Pajarito J., Araya P., Guerra F., Li Y., Liu G., Wang B., Chong Y., He M., Wang L., Liu J., Zhang X., Lai C., Jiang H., Cui S., Tao Q., Zhang Y., Yao S., Xu M., Xiao H., Hu J., Tang J., Ji H., Jiang M., Yu F., Yang X., Guo X., Wang Y., Wu L., Gao Y., Sun D., Huang X., Liu L., Li P., Jiang Y., Li H., Lu H., Zhou J., Yuan C., Qi X., Qiu F., Qian H., Wang W., Sun W., Li F., Liu R., Peng Q., Ren Z., Fan C., Wang H., Wang T., Shi F., Duan C., Chen Z., Tan X., Zhao Z., Chen J., Han T., Zhang L., Hu Q., Hou Q., Zhao X., Zeng G., Ma L., Wang F., Guo Z., Fu Y., Song Y., Tai L., Liu X., Su X., Yang Y., Dong R., Xu Y., Tian S., Cheng S., Su L., Xie X., Xu T., Geng D., Yan X., Fan H., Zhao N., Wang S., Yang J., Yan M., Li L., Li Z., Xu X., Lian Y., Sun H., Liu D., Wang N., Tang Q., Han Z., Feng L., Cui Y., Tian J., Chang H., Sun X., Liu C., Wen Z., Lin Q., Sun L., Hu B., Zou M., Bao Q., Lin X., Zhao L., Tian X., Wang X., Li X., Hao L., Duan Y., Wang R., Wei Z., Ren S., Ren H., Dong Y., Cheng Y., Liu W., Han J., Zhang Z., Zhu J., Qian J., Sun Y., Liu K., Long F., Peng X., Zhang Q., Yuan Z., Wang C., Huang M., He P., You Y., Xia J., Zhou L., Hou Y., Qi Y., Mei L., Lu R., Ping L., Zhou S., Zhang S., Zou R., Guo J., Li M., Wei W., Curtze S., Saarela M., Strbian D., Scheperjans F., De Broucker T., Henry C., Cumurciuc R., Ibos-Auge N., Zeghoudi A.-C., Pico F., Dereeper O., Simian M.-C., Boisselier C., Mahfoud A., Timsit S., Merrien F.M., Guillon B., Sevin M., Herisson F., Magne C., Ameri A., Cret C., Stefanizzi S., Klapzcynski F., Denier C., Sarov-Riviere M., Reiner P., Mawet J., Herve D., Buffon F., Touze E., Domigo V., Lamy C., Calvet D., Pasquini M., Alamowitch S., Favrole P., Muresan I.-P., Crozier S., Rosso C., Pires C., Leger A., Deltour S., Cordonnier C., Henon H., Rossi C., Zuber M., Bruandet M., Tamazyan R., Join-Lambert C., Juettler E., Krause T., Maul S., Endres M., Jungehulsing G.J., Hennerici M., Griebe M., Sauer T., Knoll K., Huber R., Knauer K., Knauer C., Raubold S., Schneider H., Hentschel H., Lautenschlager C., Schimmel E., Dzialowski I., Foerch C., Lorenz M., Singer O., Meyer Dos Santos I.M.R., Hartmann A., Hamann A., Schacht A., Schrader B., Teichmann A., Wartenberg K.E., Mueller T.J., Jander S., Gliem M., Boettcher C., Rosenkranz M., Beck C., Otto D., Thomalla G., Cheng B., Wong K.S., Leung T.W., Soo Y.O.Y., Prabhakar S., Kesavarapu S.R., Gajjela P.K., Chenna R.R., Ummer K., Basheer M., Andipet A., Jagarlapudi M.K.M., Mohammed A.U.R., Pawar V.G., Eranki S.S.K., Singh Y., Akhtar N., Borah N.C., Ghose M., Choudhury N., Ichaporia N.R., Shendge J., Khese S., Pamidimukkala V., Inbamuthaiah P., Nuthakki S.R., Tagallamudi N.M.R., Gutti A.K., Khurana D., Kesavarapu P., Jogi V., Garg A., Samanta D., Sarma G.R.K., Nadig R., Mathew T., Anandan M.A., Caterbi E., Zini A., Cavazzuti M., Casoni F., Pentore R., Falzone F., Mazzoli T., Greco L.M., Menichetti C., Coppola F., Cenciarelli S., Gallinella E., Mattioni A., Condurso R., Sicilia I., Zampolini M., Corea F., Barbi M., Proietti C., Toni D., Pieroni A., Anzini A., Falcou A., Demichele M., Klijn C.J.M., Tveiten A., Thortveit E.T., Pettersen S., Holand N., Hitland B., Johnsen S.H., Eltoft A., Wasay M., Kamal A., Iqrar A., Ali L., Begum D., Fischer R., Gama G., Fonseca L., Moreira G., Veloso L.M., Pinheiro D., Paredes L., Rozeira C., Gregorio T., Segura Martin T., Ayo O., Garcia-Garcia J., Feria Vilar I., Gomez Fernandez I., Amaro S., Urra X., Obach V., Cervera A., Silva Y., Serena J., Castellanos M., Terceno M., Van Eendenburg C., Weck A., Findling O., Ludi R., Warburton E.A., Day D., Butler N., Bumanlag E., Caine S., Steele A., Osborn M., Dodd E., Murphy P., Esisi B., Brown E., Hayman R., Baliga V.K.V., Minphone M., Kennedy J., Reckless I., Pope G., Teal R., Michael K., Manawadu D., Kalra L., Lewis R., Mistry B., Cattermole E., Hassan A., Mandizvidza L., Bamford J., Brooks H., Bedford C., Whiting R., Baines P., Hussain M., Harvey M., Fotherby K., McBride S., Bourke P., Morgan D., Jennings-Preece K., Price C., Huntley S., Riddell V.E., Storey G., Lakey R.L., Subramanian G., Jenkinson D., Kwan J., David O., Tiwari D., James M., Keenan S., Eastwood H., Shaw L., Kaye P., Button D., Madigan B., Williamson D., Dixit A., Davis J., Hossain M.O., Ford G.A., Parry-Jones A., O'Loughlin V., Jarapa R., Naing Z., Lovelock C., O'Reilly J., Khan U., Bhalla A., Rudd A., Birns J., Werring D.J., Law R., Perry R., Jones I., Erande R., Roffe C., Natarajan I., Ahmad N., Finney K., Lucas J., Mistri A., Eveson D., Marsh R., Haunton V., Fugate J.E., Lepore S.W., Zheng D., Sato S., Arima H., Heeley E., Delcourt C., Cao Y., Chalmers J., Anderson C.S., Davis S., Huang Y., Lavados P., Neal B., Parsons M.W., Lindley R., Morgenstern L., Robinson T., Stapf C., Tzourio C., Wang J.G., Chen S., Chen X.Y., Cui L., Liu Z., Lu C., Wang J., Wu S., Xu E., Yang Q., Zhang C., Zhang J., Beer R., Schmutzhard E., Redondo P., Kaste M., Soinne L., Tatlisumak T., Wartenberg K., Ricci S., Klijn K., Azevedo E., Chamorro A., Arnold M., Fischer U., Kaul S., Pandian J., Boyini H., Singh S., Rabinstein A.A., Estol C., Silva G., Olavarria V.V., Robinson T.G., Simes R.J., Bousser M.-G., Hankey G., Jamrozik K., Johnston S.C., Li S., Bailey K., Cheung T., Chintapatla S., Ducasse E., Erho T., Hata J., Holder B., Knight E., Leroux M., Sasse T., Odgers E., Walsh R., Wolfowicz Z., Chen G., Fuentes S., Peng B., Schneble H.-M., Wang M.-X., Billot L., Heritier S., Li Q., Woodward M., Abimbola S., Anderson S., Chan E., Cheng G., Chmielnik P., Leighton S., Liu J.-Y., Rasmussen B., Saxena A., Tripathy S., Armenis M., Baig M.A., Naidu B., Starzec G., Steley S., Moles A., Ruiz A., Zimmermann M., Marinho J., Alves S., Angelim R., Araujo J., Kawakami L., Bustos C., Gonzalez F., Munoz Venturelli P., Chen X., Jia R., Li N., Qu S., Shu Y., Song A., Sun J., Xiao J., Zhao Y., Huang Q., Vicaut E., Chamam A., Viaud M.-C., Dert C., Fiedler U., Jovis V., Kabla S., Marchand S., Pena A., Mallikarjuna K., Hasan N., Berge E., Sandset E.C., Forarsveen A.S., Richardson D., Kumar T., Lewin S., Poulter N., Field J., Anjum A., Wilson A., Perelmuter H., Agarie A.M., Barboza A.G., Recchia L.A., Miranda I.F., Rauek S.G., Duplessis R.J., Dewey H., Walker L., Petrolo S., Bladin C., Sturm J., Crimmins D., Griffiths D., Schutz A., Zenteno V., Miteff F., Spratt N., Kerr E., Levi C.R., Phan T.G., Ma H., Sanders L., Moran C., Wong K., Read S., Henderson R., Wong A., Hull R., Skinner G., Hand P., Yan B., Tu H., Campbell B., Blacker D.J., Wijeratne T., Pathirage M., Jasinararchchi M., Matkovic Z., Celestino S., Gruber F., Vosko M.R., Diabl E., Rathmaier S., Pfausler B., Helbok R., Fazekas F., Poltrum B., Zechner B., Trummer U., Rutgers M.P., Peeters A., Dusart A., Duray M.-C., Parmentier C., Ferrao-Santos S., Brouns R., De Raedt S., De Smedt A., Vanhooff R.-J., De Keyser J., Martins S.C.O., De Almeida A.G., Broudani R., Titton N.F., De Freitas G.R., Cardoso F.M., Giesel L.M., Lima N.A., Ferraz De Almeida A.C., Gomes R.B., Borges Dos Santos T.S., Veloso Soares E.M., Neto O.L.A., Silva G.S., Gomes D.L., De Carvalho F.A., Miranda M., Marques A., Zetola V.F., De Matia G., Lange M.C., Montes J., Reccius A., Soto A., Rivas R., Klapp C., Illanes S., Aguilera C., Castro A., Figueroa C., Benavides J., Salamanca P., Concha M.C., Pajarito J., Araya P., Guerra F., Li Y., Liu G., Wang B., Chong Y., He M., Wang L., Liu J., Zhang X., Lai C., Jiang H., Cui S., Tao Q., Zhang Y., Yao S., Xu M., Xiao H., Hu J., Tang J., Ji H., Jiang M., Yu F., Yang X., Guo X., Wang Y., Wu L., Gao Y., Sun D., Huang X., Liu L., Li P., Jiang Y., Li H., Lu H., Zhou J., Yuan C., Qi X., Qiu F., Qian H., Wang W., Sun W., Li F., Liu R., Peng Q., Ren Z., Fan C., Wang H., Wang T., Shi F., Duan C., Chen Z., Tan X., Zhao Z., Chen J., Han T., Zhang L., Hu Q., Hou Q., Zhao X., Zeng G., Ma L., Wang F., Guo Z., Fu Y., Song Y., Tai L., Liu X., Su X., Yang Y., Dong R., Xu Y., Tian S., Cheng S., Su L., Xie X., Xu T., Geng D., Yan X., Fan H., Zhao N., Wang S., Yang J., Yan M., Li L., Li Z., Xu X., Lian Y., Sun H., Liu D., Wang N., Tang Q., Han Z., Feng L., Cui Y., Tian J., Chang H., Sun X., Liu C., Wen Z., Lin Q., Sun L., Hu B., Zou M., Bao Q., Lin X., Zhao L., Tian X., Wang X., Li X., Hao L., Duan Y., Wang R., Wei Z., Ren S., Ren H., Dong Y., Cheng Y., Liu W., Han J., Zhang Z., Zhu J., Qian J., Sun Y., Liu K., Long F., Peng X., Zhang Q., Yuan Z., Wang C., Huang M., He P., You Y., Xia J., Zhou L., Hou Y., Qi Y., Mei L., Lu R., Ping L., Zhou S., Zhang S., Zou R., Guo J., Li M., Wei W., Curtze S., Saarela M., Strbian D., Scheperjans F., De Broucker T., Henry C., Cumurciuc R., Ibos-Auge N., Zeghoudi A.-C., Pico F., Dereeper O., Simian M.-C., Boisselier C., Mahfoud A., Timsit S., Merrien F.M., Guillon B., Sevin M., Herisson F., Magne C., Ameri A., Cret C., Stefanizzi S., Klapzcynski F., Denier C., Sarov-Riviere M., Reiner P., Mawet J., Herve D., Buffon F., Touze E., Domigo V., Lamy C., Calvet D., Pasquini M., Alamowitch S., Favrole P., Muresan I.-P., Crozier S., Rosso C., Pires C., Leger A., Deltour S., Cordonnier C., Henon H., Rossi C., Zuber M., Bruandet M., Tamazyan R., Join-Lambert C., Juettler E., Krause T., Maul S., Endres M., Jungehulsing G.J., Hennerici M., Griebe M., Sauer T., Knoll K., Huber R., Knauer K., Knauer C., Raubold S., Schneider H., Hentschel H., Lautenschlager C., Schimmel E., Dzialowski I., Foerch C., Lorenz M., Singer O., Meyer Dos Santos I.M.R., Hartmann A., Hamann A., Schacht A., Schrader B., Teichmann A., Wartenberg K.E., Mueller T.J., Jander S., Gliem M., Boettcher C., Rosenkranz M., Beck C., Otto D., Thomalla G., Cheng B., Wong K.S., Leung T.W., Soo Y.O.Y., Prabhakar S., Kesavarapu S.R., Gajjela P.K., Chenna R.R., Ummer K., Basheer M., Andipet A., Jagarlapudi M.K.M., Mohammed A.U.R., Pawar V.G., Eranki S.S.K., Singh Y., Akhtar N., Borah N.C., Ghose M., Choudhury N., Ichaporia N.R., Shendge J., Khese S., Pamidimukkala V., Inbamuthaiah P., Nuthakki S.R., Tagallamudi N.M.R., Gutti A.K., Khurana D., Kesavarapu P., Jogi V., Garg A., Samanta D., Sarma G.R.K., Nadig R., Mathew T., Anandan M.A., Caterbi E., Zini A., Cavazzuti M., Casoni F., Pentore R., Falzone F., Mazzoli T., Greco L.M., Menichetti C., Coppola F., Cenciarelli S., Gallinella E., Mattioni A., Condurso R., Sicilia I., Zampolini M., Corea F., Barbi M., Proietti C., Toni D., Pieroni A., Anzini A., Falcou A., Demichele M., Klijn C.J.M., Tveiten A., Thortveit E.T., Pettersen S., Holand N., Hitland B., Johnsen S.H., Eltoft A., Wasay M., Kamal A., Iqrar A., Ali L., and Begum D.

Abstract

Background: The kidney-brain interaction has been a topic of growing interest. Past studies of the effect of kidney function on intracerebral hemorrhage (ICH) outcomes have yielded inconsistent findings. Although the second, main phase of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) suggests the effectiveness of early intensive blood pressure (BP) lowering in improving functional recovery after ICH, the balance of potential benefits and harms of this treatment in those with decreased kidney function remains uncertain. Study Design: Secondary analysis of INTERACT2, which randomly assigned patients with ICH with elevated systolic BP (SBP) to intensive (target SBP < 140 mm Hg) or contemporaneous guideline-based (target SBP < 180 mm Hg) BP management. Setting & Participants: 2,823 patients from 144 clinical hospitals in 21 countries. Predictors Admission estimated glomerular filtration rates (eGFRs) of patients were categorized into 3 groups based on the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation: normal or high, mildly decreased, and moderately to severely decreased (>90, 60-90, and <60 mL/min/1.73 m2, respectively). Outcome(s): The effect of admission eGFR on the primary outcome of death or major disability at 90 days (defined as modified Rankin Scale scores of 3-6) was analyzed using a multivariable logistic regression model. Potential effect modification of intensive BP lowering treatment by admission eGFR was assessed by interaction terms. Result(s): Of 2,623 included participants, 912 (35%) and 280 (11%) had mildly and moderately/severely decreased eGFRs, respectively. Patients with moderately/severely decreased eGFRs had the greatest risk for death or major disability at 90 days (adjusted OR, 1.82; 95% CI, 1.28-2.61). Effects of early intensive BP lowering were consistent across different eGFRs (P = 0.5 for homogeneity). Limitation(s): Generalizability issues arising from a clinical tri

Published
2016

46. Natural Variation Identifies ICARUS1, a Universal Gene Required for Cell Proliferation and Growth at High Temperatures in Arabidopsis thaliana

Author

Bomblies, K, Zhu, W, Ausin, I, Seleznev, A, Mendez-Vigo, B, Xavier Pico, F, Sureshkumar, S, Sundaramoorthi, V, Bulach, D, Powell, D, Seemann, T, Alonso-Blanco, C, Balasubramanian, S, Bomblies, K, Zhu, W, Ausin, I, Seleznev, A, Mendez-Vigo, B, Xavier Pico, F, Sureshkumar, S, Sundaramoorthi, V, Bulach, D, Powell, D, Seemann, T, Alonso-Blanco, C, and Balasubramanian, S

Abstract

Plants are highly sensitive to environmental changes and even small variations in ambient temperature have severe consequences on their growth and development. Temperature affects multiple aspects of plant development, but the processes and mechanisms underlying thermo-sensitive growth responses are mostly unknown. Here we exploit natural variation in Arabidopsis thaliana to identify and characterize novel components and processes mediating thermo-sensitive growth responses in plants. Phenotypic screening of wild accessions identified several strains displaying pleiotropic growth defects, at cellular and organism levels, specifically at high ambient temperatures. Positional cloning and characterization of the underlying gene revealed that ICARUS1 (ICA1), which encodes a protein of the tRNAHis guanylyl transferase (Thg1) superfamily, is required for plant growth at high temperatures. Transcriptome and gene marker analyses together with DNA content measurements show that ICA1 loss-of-function results in down regulation of cell cycle associated genes at high temperatures, which is linked with a block in G2/M transition and endoreduplication. In addition, plants with mutations in ICA1 show enhanced sensitivity to DNA damage. Characterization of additional strains that carry lesions in ICA1, but display normal growth, shows that alternative splicing is likely to alleviate the deleterious effects of some natural mutations. Furthermore, analyses of worldwide and regional collections of natural accessions indicate that ICA1 loss-of-function has arisen several times independently, and that these occur at high frequency in some local populations. Overall our results suggest that ICA1-mediated-modulation of fundamental processes such as tRNAHis maturation, modify plant growth responses to temperature changes in a quantitative and reversible manner, in natural populations.

Published
2015

47. EVALUACIÓN DE LA COMPOSICIÓN NUTRICIONAL, ANTINUTRICIONAL Y BIODISPONIBILIDAD IN VITRO DE DIFERENTES EXTRACTOS FOLIARES

Author

Pico F, Sayda Milena, Gutiérrez, Dayron, Aragón G, Ingrid, Escobar S, Andrés, Ortiz, Darwin, Sánchez, Teresa, Imbachí N, Paola, and Pachón, Helena

Subjects
componentes antinutricionales, concentrado de hoja, foliar extract, nutrients, biodisponibilidad in vitro, antinutrient, componentes nutricionales, in vitro bioavailability, leaf concentrate, Extracto foliar
Abstract

Los extractos foliares (EF) son utilizados como complemento nutricional en países como Nicaragua y Tanzania. Se evaluaron hojas y EF de yuca, fríjol, batata y alfalfa, y se cuantificó los componentes nutricionales, antinutricionales y biodisponibilidad por métodos in vitro. En promedio (DE), el EF de fríjol tiene una elevada concentración de hierro (1006,23 (8,49) mg/kg); el EF de yuca tiene alta concentración de zinc (110,65 (6,72) mg/ kg) y proteína soluble (34,23 (3,81) g/kg). Así mismo, la digestibilidad in vitro de proteína en los EFs de yuca, fríjol y alfalfa fueron superiores a 71,18%; hierro dializable in vitro menor a 2,29%; la relación molar fitato:zinc inferior a 0,08 y la bioaccesibilidad all-trans-β -caroteno superior a 23,85%. Estos valores sugieren una alta asimilación de proteína, zinc y all-trans-β -caroteno, y una baja asimilabilidad de hierro. Los EFs pueden ser una alternativa nutricional en la alimentación en países que carecen de diversificación alimentaria. Foliar extracts (FEs) are an alternative to address food and nutrition insecurity. FEs and leaves of cassava, bean, sweet potato and alfalfa were evaluated for nutrient and antinutrient composition and in vitro nutrient bioavailability. Bean FE had a high average ± (SD) iron concentration (1006 ± 8.49 mg/kg), as did cassava FE for zinc (110.1 ± 6.72 mg/kg) and soluble protein (34.23 ± 3.81 g/kg) concentration. For the cassava, bean and alfalfa FEs in vitro protein digestibility was greater than 71.18%; in vitro iron dialyzability was less than 2.29%; the phytate:zinc molar ratio was less than 0.08, and the in vitro all-trans-β-carotene bioavailability was greater than 23.85%. These values suggest a high protein, zinc and all-trans- β -carotene bioavailability and a low iron bioavailability. FEs can be a nutritious alternative for those countries with low dietary diversity.

Published
2011

49. Ruthenium oxide/carbon composites having a microporous carbon or a mesoporous carbon as support. A comparative study as supercapacitor electrodes

Author

Pico, F., Morales, E., Fernández, J. A., Álvarez Centeno, Teresa, Ibáñez, Joaquín, Rojas, R. M., Amarilla, José Manuel, and Rojo, J. M.

Subjects
mesoporous carbon, ruthenium oxide, microporous carbon
Abstract

Composites have been prepared by depositing nanoparticles of RuO2.xH2O (1-5 nm) on two carbons: a microporous carbon (1.3 nm of pore size) and a mesoporous carbon (11 nm of pore size). The composites have been obtained by two ways: (i) way A consisting of an accumulative impregnation treatment of the carbons with RuCl3.0.5H2O solution, and (ii) way B consisting of a impregnation of the carbons with Ru(acac)3 vapour. The way B leads to supported RuO2.xH2O particles that appear more crystalline and more heterogeneous in size than those obtained by way A. Specific surface area and specific capacitance of the composites have been measured. The two magnitudes, which are analysed as a function of the RuO2 content, show very different dependences for the composites derived from the two carbons. They are discussed on the basis of the size of the supported RuO2.xH2O particles in comparison to the size of the carbon pores., Project of reference MAT2005- 01606 is gratefully acknowledged. F. Pico thanks for a contract associated with that project.

Published
2009

50. Rationale and design of a randomized, double-blind, parallel-group study of terutroban 30 mg/day versus aspirin 100 mg/day in stroke patients: the prevention of cerebrovascular and cardiovascular events of ischemic origin with terutroban in patients with a history of ischemic stroke or transient ischemic attack (PERFORM) study

Author

Bousser, M, Amarenco, P, Chamorro, A, Fisher, M, Ford, I, Fox, K, Hennerici, M, Mattle, H, Rothwell, P, Julian, D, Fieschi, G, Fieschi, C, Boysen, G, Pocock, S, Conard, J, Orgogozo, J, Inzitari, D, Erkinjuntti, T, Pasquier, F, O'Brien, J, Mas, J, Gueret, P, Lenzi, G, Leys, D, Lopez Sendon, J, Norrving, B, Ferro, J, Thygesen, K, Cowpply, B, P, Ameriso, S, Donnan, D, Lang, W, Thijs, V, Fernandes, J, Stamenova, P, Teal, P, Lavados, P, Lu, C, Poljakovic, Z, Kalita, Z, Kaste, M, Moulin, T, Vemmos, K, Diener, H, Wong, L, Nagy, Z, Chopra, J, Mccormack, P, Gensini, G, Budrys, V, Droste, D, Tan, K, Benomar, A, Cantu Brito, C, Barber, A, Koudstaal, P, Thomassen, L, Czlonkowska, A, Cunha, L, Bajenaru, O, Yakhno, N, Chen, C, Lisy, L, Zvan, B, Bryer, A, Kim, J, Vivancos, J, Wahlgren, N, Liu, S, Poungvarin, N, Hentati, F, Bahar, S, Mischenko, T, Lees, K, Abdel Masih, M, Barboza, A, Cirio, J, Crespo, E, Escaray, G, Esnaola, M, Rojas Estol, C, Ferrari, J, Fraiman, H, Garrote, M, Gatto, E, Giannaula, R, Gori, H, Herrera, G, Ioli, P, Losano, J, Povedano Reich, E, Rey, R, Rotta Escalante, R, Saredo, G, Zurru, M, Anderson, C, Bladin, C, Crimmins, D, Davis, S, Donnan, G, Dunbabin, D, Frayne, J, Gates, P, Hankey, G, Helme, R, Herkes, G, Karrasch, J, Kimber, T, Jannes, J, Landau, P, Levi, C, Lueck, C, Markus, R, Phan, T, Schwartz, R, Schultz, D, Blacker, D, Read, S, Williams, M, Aichner, F, Auff, E, Bancher, C, Binder, H, Brainin, M, Brucke, T, Eggers, C, Fertl, E, Ladurner, G, Lalouschek, W, Mamoli, B, Mitrovic, N, Noisternig, G, Schmidt, R, Vosko, M, Willeit, J, Zaruba, E, Boon, P, Bourgeois, P, Caekebeke, J, Cals, N, Cras, P, Desfontaines, P, De Deyn, P, Dieudonne, L, De Klippel, N, Laloux, P, Maertens de Noordhout, A, Merlevede, K, Michotte, A, Pandolfo, M, Peeters, A, Peeters, D, Tack, P, Van Buggenhout, E, Van Landegem, W, Vanhooren, G, Vermylen, P, Annes, M, Brondani, R, De Carvalho, J, Cendes, F, Fabio, S, Ferraz, A, De Freitas, G, Gagliardi, R, Gomes Neto, A, Haussen, S, Kowacs, P, Martins, S, Minelli, C, Moro, C, Noujaim, J, Rocha, M, Da Silva, M, Silveira, J, Yamamoto, F, Zetola, V, Baldaranov, D, Deleva, N, Haralanov, L, Milanov, I, Mintchev, D, Petrova, N, Shotekov, P, Stamenov, B, Zahariev, Z, Arts, R, Bayer, N, Beaudry, M, Berger, L, Bozek, C, Collier, T, Cote, R, Desai, H, Durocher, A, Hachinski, V, Hill, M, Hoppe, B, Howse, D, Mackey, A, Maharaj, M, Minuk, J, Moddel, G, Novak, D, Penn, A, Rabinovitch, H, Selchen, D, Shuaib, A, Silva, J, Silver, F, Spence, D, Stotts, G, Tamayo, A, Teitelbaum, J, Veloso, F, Voll, C, Winder, T, Barrientos Uribe, N, Galdames Poblete, D, Garcia Figueroa, P, Gasic Yaconi, K, Jaramillo Munoz, A, Lavados Germain, P, Lavados Montes, M, Nancupil Bello, C, Prina Pacheco, L, Vargas Canas, A, Venegas, F, Chen, P, H, Cheng, Y, Cui, L, Di, Q, Dong, Q, Fan, D, Feng, H, Huang, Y, Li, J, Li, W, Li, Z, Lin, H, Liu, M, Miao, L, Ren, H, Wang, Y, Wu, J, Zhang, W, Zhao, G, Zhao, H, Zhou, H, Antoncic, I, Demarin, V, Lusic, I, Pavlicek, I, Soldo Butkovic, S, Bar, M, Bauer, J, Kalina, M, Kanovsky, P, Jura, R, Neumann, J, Rektor, I, Skoda, O, Vaclavik, D, Eerola, A, Hillbom, M, Kinnunen, E, Koivisto, K, Numminen, H, Rissanen, A, Roine, R, Sivenius, J, Alamowitch, S, Autret, A, Avendano, S, Bataillard, M, Berthier, E, Besson, G, Bille Turc, F, Boulliat, J, Boulesteix, J, Brosset, C, Cesaro, P, Albucher, J, Clavelou, P, Colamarino, R, Crassard, I, de Broucker, T, de Bray, J, Desbordes, P, Diot, E, Ducrocq, X, Ellie, E, Faucheux, J, Giroud, M, Godefroy, O, Guillon, B, Huttin, H, Just, A, Lamy, C, Lejeune, P, Lucas, C, Macian Montoro, F, Mackowiak, A, Maillet Vioud, M, Pico, F, Milandre, L, Milhaud, D, Malbec, M, Neau, J, Pinel, J, Robin, C, Rodier, G, Rosolacci, T, Rouanet, F, Rouhart, F, Sablot, D, Servan, J, Smadja, D, Trouillas, P, Valance, J, Viader, F, Viallet, F, Wolff, V, Zagnoli, F, Zuber, M, Angerer, M, Becker, U, Berlit, P, Berrouschot, J, Biniek, R, Bitsch, A, Brodhun, R, Dichgans, M, Druschky, K, Dux, R, Faiss, J, Ferbert, A, Gahn, G, Grotemeyer, K, Goertler, M, Grau, A, Griewing, B, Grond, M, Haan, J, Haberl, R, Hamann, G, Hamer, H, Harms, L, Heide, W, Henningsen, H, Hetzel, A, Hoffmann, F, Huber, R, Isenmann, S, Jander, S, Joerg, J, Kaps, M, Kastrup, A, Kessler, C, Koehler, W, Koelmel, H, Lichy, C, Luckner, K, Malessa, R, Mallmann, A, Meyding Lamade, U, Molitor, H, Mueller Jensen, A, Muellges, W, Noth, J, Nueckel, M, Ochs, G, Poppert, H, Roether, J, Rosenkranz, M, Sander, D, Schaebitz, W, Schlachetzki, F, Schlegel, U, Schmid, E, Schneider, D, Schwarz, M, Seidel, G, Sieble, M, Sliwka, U, Stingele, R, Stoegbauer, F, Szabo, K, Topper, R, Treib, J, Weissenborn, K, Widder, B, Witte, O, Karageorgiou, K, Mitsikostas, D, Papadimitriou, A, Papathanasopoulos, P, Chan, H, Ng, P, Tsoi, T, Bartos, L, Csanyi, A, Csiba, L, Csornai, M, Dioszeghy, P, Fazekas, A, Harcos, P, Horvath, S, Kaposzta, Z, Kerenyi, L, Kincses, J, Koves, A, Nikl, J, Panczel, G, Pongracz, E, Sebestyen, K, Semjen, J, Szabo, M, Szegedi, N, Valikovics, A, Varszegi, R, Vecsei, L, Borah, N, Ichaporia, N, Kaul, S, Meenakshi Sundaram, S, Mehndiratta, M, Misra, U, Murthy, J, Nayak, D, Poncha, F, Shah, A, Singh, G, Srinivasa, R, Venkateswarlu, K, Wadia, R, Collins, R, Harbison, J, Hickey, P, Kelly, P, Murphy, S, Adami, A, Agnelli, G, Agostoni, E, Anzola, G, Arnaboldi, M, Bassi, P, Billo, G, Bottacchi, E, Bovi, P, Cappa, S, Cappelletti, C, Carolei, A, Cavallini, A, Chiodo Grandi, F, Comi, G, Consoli, D, Corsi, F, Costanzo, E, De Falco, F, Devetag, F, Di Lazzaro, V, Di Piero, V, Diomedi, M, Fattorello Salimbeni, C, Federico, F, Feleppa, M, Ferrarese, C, Gandolfo, C, Giaccaglini, E, Giaquinto, S, Giobbe, D, Giometto, B, Greco, G, Guidetti, D, Guidotti, M, Iudice, A, Lembo, G, Marengo, C, Marini, P, Melis, M, Micieli, G, Musolino, R, Mutani, R, Neri, G, Parati, E, Pastore, L, Porazzi, D, Prati, P, Procaccianti, G, Rasura, M, Rossini, P, Santilli, I, Semplicini, A, Silvestrini, M, Tanganelli, P, Tedeschi, G, Tezzon, F, Tola, M, 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Subjects
perform study, Male, Thromboxane, International Cooperation, Receptors, Thromboxane, antiplatelet therapy, terutroban, Cardiovascular Disease, Receptors, 80 and over, Stroke, Aged, 80 and over, Aspirin, Ischemic Attack, Transient, Ischemic Attack, Transient, Double-Blind Method, Endpoint Determination, Dose-Response Relationship, Drug, Humans, Aged, Propionates, Naphthalenes, Treatment Outcome, Platelet Aggregation Inhibitors, Cardiovascular Diseases, Middle Aged, Female, Propionic Acids, Neurology, Terutroban, Anesthesia, tp receptor antagonist, stroke, secondary prevention, aspirin, Cardiology, Platelet aggregation inhibitor, Settore MED/26 - Neurologia, stroke prevention, Drug, Cardiology and Cardiovascular Medicine, medicine.drug, Human, medicine.medical_specialty, Dose-Response Relationship, Internal medicine, medicine, Dementia, In patient, business.industry, Platelet Aggregation Inhibitor, schemic, medicine.disease, DementiaI, transient ischemic attack, Ischemic stroke, Human medicine, Neurology (clinical), business, Propionic Acid, Naphthalene
Abstract

Background: Ischemic stroke is the leading cause of mortality worldwide and a major contributor to neurological disability and dementia. Terutroban is a specific TP receptor antagonist with antithrombotic, antivasoconstrictive, and antiatherosclerotic properties, which may be of interest for the secondary prevention of ischemic stroke. This article describes the rationale and design of the Prevention of cerebrovascular and cardiovascular Events of ischemic origin with teRutroban in patients with a history oF ischemic strOke or tRansient ischeMic Attack (PERFORM) Study, which aims to demonstrate the superiority of the efficacy of terutroban versus aspirin in secondary prevention of cerebrovascular and cardiovascular events. Methods and Results: The PERFORM Study is a multicenter, randomized, double-blind, parallel-group study being carried out in 802 centers in 46 countries. The study population includes patients aged ≥55 years, having suffered an ischemic stroke (≤3 months) or a transient ischemic attack (≤8 days). Participants are randomly allocated to terutroban (30 mg/day) or aspirin (100 mg/day). The primary efficacy endpoint is a composite of ischemic stroke (fatal or nonfatal), myocardial infarction (fatal or nonfatal), or other vascular death (excluding hemorrhagic death of any origin). Safety is being evaluated by assessing hemorrhagic events. Follow-up is expected to last for 2–4 years. Assuming a relative risk reduction of 13%, the expected number of primary events is 2,340. To obtain statistical power of 90%, this requires inclusion of at least 18,000 patients in this event-driven trial. The first patient was randomized in February 2006. Conclusions: The PERFORM Study will explore the benefits and safety of terutroban in secondary cardiovascular prevention after a cerebral ischemic event.

Published
2009

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