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2. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
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Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn RJ, Novo S, Krum H, Varigos J, Siostrzonek P, Sinnaeve P, Gotcheva N, Yong H, Urina-Triana M, Milicic D, Vettus R, Manolis AJ, Wyss F, Sigurdsson A, Fucili A, Veze I, Petrauskiene B, Salvador L, Klemsdal TO, Medina F, Budaj A, Otasevic P, Lainscak M, Seung KB, Commerford P, Donath M, Hwang JJ, Kultursay H, Bilazarian S, East C, Forgosh L, Harris B, Ligueros M, Bohula E, Charmarthi B, Cheng S, Chou S, Danik J, McMahon G, Maron B, Ning M, Olenchock B, Pande R, Perlstein T, Pradhan A, Rost N, Singhal A, Taqueti V, Wei N, Burris H, Cioffi A, Dalseg AM, Ghosh N, Gralow J, Mayer T, Rugo H, Fowler V, Limaye AP, Cosgrove S, Levine D, Lopes R, Scott J, Hilkert R, Tamesby G, Mickel C, Manning B, Woelcke J, Tan M, Manfreda S, Ponce T, Kam J, Saini R, Banker K, Salko T, Nandy P, Tawfik R, O’Neil G, Manne S, Jirvankar P, Lal S, Nema D, Jose J, Collins R, Bailey K, Blumenthal R, Colhoun H, Gersh B, Abreu M, Actis MV, Aiub J, Aiub F, Albisu J, Alvarisqueta A, Avalos V, Barreto M, Berli MA, Blumberg C, Bocanera M, Botta C, Bowen L, Budassi N, Buhlman S, Westberg JC, Carabajal T, Caruso G, Casala J, Cendali G, Coloma G, Berra FC, Cuneo C, Degennaro N, Dellasa M, Diaz M, Dos Santos P, Espinosa V, Facello A, Facello M, Farias E, Fernandez AA, Ferrari V, Pacora FF, Flores GS, Franco M, Gabito A, Viola HG, Garcia F, Garcia Duran R, Garcia Pinna J, Glenny J, Godoy Sanchez M, Grosse A, Guzman P, Hasbani E, Hominal M, Ibañez J, Jure H, Jure D, Vico ML, Liniado G, Luciardi H, Luquez H, Maehara G, Maffei L, Majul C, Mallagray M, Marinaro S, Martinez J, Massaccesi R, De Los Milagros Had M, Azize GM, Montana O, Montenegro E, Morell Y, Muntaner J, Navarrete S, Olmedo M, Paganini M, Paz S, Perez Manghi F, Piskorz D, Polato C, Recoaro R, Romano A, Salinger M, Sanchez A, Saravia MA, Sarjanovich R, Scaro G, Schiavi LB, Soler J, Tinnirello V, Tomassi A, Valle M, Vallejo MA, Venturini C, Marcela Wenetz LM, Yossen M, Zaidman C, Zalazar L, Zangroniz P, Amerena J, Brady L, Colquhoun D, Eccleston D, Ferreira-Jardim A, French J, Jayasinghe R, Mcintosh C, Ord M, Plotz M, Purnell P, Roberts-Thomson P, Schultz C, Shanahan T, Tan R, Taverner P, Turner F, Vibert J, Vorster M, William M, Youssef G, Bergler-Klein J, Brath H, Brodmann M, Fliesser-Goerzer E, Haider K, Heeren G, Hiden C, Mandic L, Paulweber B, Ploechl A, Prenner A, Steringer-Mascherbauer R, Strohner-Kaestenbauer H, Barbato E, Bouvy C, Briké C, Charlier F, Cools F, De Knijf K, De Wolf L, Delforge M, Deweerdt N, Gits F, Goffinet C, Hermans K, Hollanders G, Mestdagh I, Pirenne B, Servaes V, Simons N, Tahon S, Theunissen E, Van Genechten G, Vervoort G, Vissers C, Vranckx P, Vrolix M, Abib E Jr, Abrantes J, Araujo Fonseca M, Barbosa E, Barroso W, Barroso A, Bodanese L, Botelho R, Costa Amorim R, Da Costa F, Da Silva A, Da Silva O Jr, Da Silva D Jr, Ferreira Dos Santos T, Dos Santos F, Dos Santos A, Duda N, Feitosa G, Felario Junior GA, Ferraz R, Filho P, Fonseca A, Wanderley FF, Freitas E, Fucci F, Marengo Garcia De Carvalho L, Hernandez M, Hettwer Magedanz E, Julião K, Kormann A, Lameira A, Lima F, Lino E, Maia L, Manenti E, Marchi AL, Fischer SM, Michalaros Y, Moraes J Jr, Moreira L, Pagnan M, Pesce F, Pinheiro L, Rassi S, Reis G, Reis H, Resende I, Roel A, Ruschel K, Saporito W, Saraiva JF, Seroqui M, Silva R, Unterkircher B, Vicente C, Vieira N, Xavier JP, Zucchetti C, Angelova I, Dimitrov G, Genova D, Gospodinov K, Goudev A, Grigorova V, Hristova K, Makedonska JJ, Katova T, Kostov K, Lazov P, Manov E, Manukov I, Manukov D, Milanova M, Kabakchieva VM, Petrov D, Petrusheva T, Pramatarova I, Raev D, Runev N, Sirakova-Taseva A, Tisheva-Gospodinova S, Todorova A, Tzekova M, Yakovova S, Yanev T, 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Winkelmann B, Winkler J, Wistuba T, Woehrle J, Wohnlich T, Wolf S, Woyczak D, Wrage P, Zirlik A, Anadiotis A, Chachalis G, Dermitzakis A, Kafarakis P, Kaldara E, Kolokathis F, Kostakou P, Lekakis J, Manolis A, Mantas I, Megalou A, Milkas A, Nanas J, Olympios CD, Patsilinakos S, Perperis A, Poulimenos L, Saloustros I, Tsioufis K, Tsorbatzoglou K, Vardas P, Zarifis I, Aguilar M, Arango JL, Borrayo NA, Corona V, Guerrero A, Guzman I, Haase F, De Krumbach L, Montenegro P, Munoz R, Munoz N, Paniagua A, Solares A, Vogel M, Anita S, Blazsek Z, Decsi K, Fulop T, Hangyal T, Hegedus V, Kalina A, Karakai H, Katona A, Kiss RG, Kovacs A, Laszlo Z, Lupkovics G, Medvegy M, Merkely B, Mihaly N, Nagy AC, Dékány JN, Nikoletta P, Noori E, Penzes J, Poor F, Sarszegi Z, Simay A, Simon J, Szakal I, Szatmarine V, Szocs A, Zilahi Z, Karsai XZ, Andersen K, Sigurdadottir E, Skuladottir F, Abdullakutty J, Abhaichand R, Abhyankar A, Agarwal DK, Aggarwal RK, Ahire N, Awasthi AK, Babu R, Bai A, Bali HK, Banker D, 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Bergholtz T, Blom KB, Boman K, Boström PÅ, Curiac D, Jensen ED, Dahlen G, Davidsson K, Duckert A, Hansson A, Härstedt N, Henriksson A, Olsson GH, Johansson K, Jonsson JE, Knutsson A, Lindholm CJ, Lönnberg I, Lundqvist M, Mellberg L, Moodh J, Mooe T, Olofsson M, Risenfors M, Rönndahl M, Sundelin R, Suorra I, Torgersruud M, Torstensson I, Chang KC, Chen CP, Chen ZC, Chen MH, Cheng SM, Cheng JJ, Fang CY, Ho CJ, Hsieh IC, Huang PH, Huang A, Kuo JY, Lai WT, Lee SC, Li YH, Lin T, Liu HM, Tsai MC, Tsao HM, Tzong L, Ueng KC, Wang YL, Wang HC, Wang CP, Yang CC, Abaci F, Birdane A, Yilmaz MB, Asim Oktay AO, Kan G, Koldas N, Ozcan IT, Sahin M, Sahin T, Saka B, Tekten T, Ucar N, Uresin S, Yigit Z, Arif I, Bakhai A, Baksi A, Blagdon M, Brickman T, Brown N, Burton M, Burton J, Chaggar S, Chung A, Collier D, Covell W, Crawford G, Davies N, Davies M, Dayer M, Doughty A, Duff J, Dwenger E, Fisher J, Fitzpatrick L, Garner K, Glover J, Haughton G, Ilsley M, Ivan P, Voyzey EJ, Keenan S, Kelt T, Knight J, Kondagunta V, Lang C, Lee K, Lim L, Macdonald J, Mathew A, Mckenzie A, Mckibbin A, Michalska A, Pagett K, Pogson A, Price R, Price D, Procter K, Pye M, Redfearn H, Rewbury J, Ryding A, Sattar N, Sharp A, Shaw P, Simpson H, Smith W, Squire I, Storey R, Teenan M, Thomas H, Townend J, Trevelyan J, Wakeling J, Walukiewicz P, Wilkinson S, Zaman A, Acevedo L, Benton J, Abbate A, Aboufakher R, Acampora M, Acampora D, Aceto L, Acevedo B, Acheatel R, Adams M, Adams A, Ahmad I, Ahmed SH, Aish B, Akyea-Djamson A, Al Joundi T, Alcide P, Alfieri A, Alfonso T, Alfrey A, Allen J, Alllison DC, Almaliky T, Amos A, Angiolillo D, Antolick A, Ara M, Aragorn L, Arevalo S, Armas E, Arthur A, Asafu-Adjaye N, Ashcom T, Ashford M, Aslam A, Ather N, Atieh M, Aull L, Ayala M, Azizad M, Backer T, Baehl S, Bailey S, Bair S, Baker C, Ballmajo M, Pieretti HB, Baquero A, Barnett S, Baron S, Bartkowiak A, Bashir K, Beall K, Beauregard LA, Sarah S, Beckett L, Belejchak P, Bendelow T, Bender D, Benjamin S, Berdoff R, 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A, Pagett K, Pogson A, Price R, Price D, Procter K, Pye M, Redfearn H, Rewbury J, Ryding A, Sattar N, Sharp A, Shaw P, Simpson H, Smith W, Squire I, Storey R, Teenan M, Thomas H, Townend J, Trevelyan J, Wakeling J, Walukiewicz P, Wilkinson S, Zaman A, Acevedo L, Benton J, Abbate A, Aboufakher R, Acampora M, Acampora D, Aceto L, Acevedo B, Acheatel R, Adams M, Adams A, Ahmad I, Ahmed SH, Aish B, Akyea-Djamson A, Al Joundi T, Alcide P, Alfieri A, Alfonso T, Alfrey A, Allen J, Alllison DC, Almaliky T, Amos A, Angiolillo D, Antolick A, Ara M, Aragorn L, Arevalo S, Armas E, Arthur A, Asafu-Adjaye N, Ashcom T, Ashford M, Aslam A, Ather N, Atieh M, Aull L, Ayala M, Azizad M, Backer T, Baehl S, Bailey S, Bair S, Baker C, Ballmajo M, Pieretti HB, Baquero A, Barnett S, Baron S, Bartkowiak A, Bashir K, Beall K, Beauregard LA, Sarah S, Beckett L, Belejchak P, Bendelow T, Bender D, Benjamin S, Berdoff R, Berger V, Bergeron P, Berk M, Bernstein M, Binns Y, Bitzer V, Blahey M, Bloch S, Bluemel J, Boffetti P, Boley K, Bonner J, Boudreaux R, Boulanger K, Bradley A, Bramlet D, Bredlau C, Briggs S, Brousalis L, Brown S, Brown C, Buchannan C, Burke W, Burley T, Burton C, Burtt D, Byars W, Caballero-Valiente B, Carr K, Halliwell TC, Castillo J, Cei L, Cerda L, Chambers J, Chamblee T, Chattin W, Chee L, Chen YC, Cherlin R, Cheung D, Chiodi L, Christensen L, Christenson S, Cislowski D, Clavier-Firmin C, Colfer H, Colvin T, Cosgrove N, Covert C, Cox B, Cox R, Craig W, Crandall L, Crepps K, Cromer M, Cruz H, Cruz H, Cruz M, Cucher F, Damron M, Dave K, Dave B, Davis M, Davis B, Dawkins-Hughes S, Dean J, Debnam S, Defosse C, Dehning M, Dela Llana A, Dellorso M, Denham D, Desalle D, Dettmer M, Dhawan M, Diago M, Dicken T, Diederich C, Diederich M, Diehl R, Digangi D, Diller P, Dimattia M, Dodds G, Doggett J, Donahue K, Doughty L, Dragutksy B, Dreese M, Dunhurst F, Dunn D, Dutka C, Earl J, Eaton C, Eaves W, Ebeling K, Eder F, Edgerton L, Edillo C, Edwards J, Edwards T, Einhorn D, El Hafi S, 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Hodnett P, Hoffman M, Hogan C, Holmes Z, Rees DH, Hotchkiss D, Huang P, Humbert J, Hutchens E, Iachini K, Ibarra M, Igbokidi O, Ilahi T, Imbrognio M, Ipp E, Iteld B, Jacques G, Jafri A, Jafry B, Jardula M, Jefferson D, Jenkins R, Johnson E, Johnson J, Jones S, Kawahara M, Kelehan S, Kelly R, Kendall T, Kereiakes D, Khan M, Khan S, Kick J, Kimmel M, King T, King A, Kirkland S, Kissel S, Kitchens D, Klein P, Klugherz B, Korban E, Koren M, Korte M, Kostis J, Kotek L, Kozak M, Kreutter F, Kusnick B, Labovitz R, Lail J, Lamance J, Lamas G, Lambert J, Lambert C, Landzberg J, Langdon J, Lavoie W, Ledger G, Lee T, Lee K, Lehman R, Leimbach W, Lennard M, Lepor N, Lester F, Levin P, Levinson L, Lewis D, Lillo J, Link L, Long C, Longaker R, Lorch G, Lucksinger G, Lynd S, Rhudy JM, Madder R, Magness K, Maheshwari A, Alan A, Malek M, Maletz L, Malhotra V, Malhotra S, Mandviwala M, Mani CK, Manuel J, Marchelletta N, Marshall L, Marsters M, Martin L, Martinez E, Mavromatis K, Maynard R, Mays M, Mays 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M., Everett, B. M., Thuren, T., Macfadyen, J. G., Chang, W. H., Ballantyne, C., FONSECA E PIRES, CARLOS EDUARDO, Nicolau, J., Koenig, W., Anker, S. D., Kastelein, J. J. P., Cornel, J. H., Pais, P., Pella, D., Genest, J., Cifkova, R., Lorenzatti, A., Forster, T., Kobalava, Z., Vida-Simiti, L., Flather, M., Shimokawa, H., Ogawa, H., Dellborg, M., Rossi, P. R. F., Troquay, R. P. T., Libby, P., Glynn R., J, CANTOS Trial, Group, Perrone, Filardi, P, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, and ACS - Atherosclerosis & ischemic syndromes
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0301 basic medicine ,030204 cardiovascular system & hematology ,law.invention ,0302 clinical medicine ,c-reactive protein ,Randomized controlled trial ,law ,Cardiovascular Disease ,middle aged ,double-blind method ,antibodies ,Myocardial infarction ,humans ,Stroke ,interleukin-1beta ,biology ,Antibodies, Monoclonal ,drug ,General Medicine ,Lipid ,Aged ,anti-inflammatory agents ,monoclonal ,humanized ,atherosclerosis ,cardiovascular diseases ,dose-response relationship ,female ,incidence ,infections ,lipids ,male ,myocardial infarction ,neutropenia ,secondary prevention ,stroke ,Anti-Inflammatory Agent ,aged ,Editorial ,Atherosclerosi ,Monoclonal ,Human ,medicine.drug ,medicine.medical_specialty ,Neutropenia ,Antibodies, Monoclonal, Humanized ,Infections ,Placebo ,antibodies, monoclonal ,dose-response relationship, drug ,infection ,medicine (all) ,03 medical and health sciences ,Internal medicine ,medicine ,Dose-Response Relationship, Drug ,business.industry ,Antiinflammatory Therapy, Canakinumab, for Atherosclerotic Disease ,C-reactive protein ,medicine.disease ,Surgery ,Canakinumab ,030104 developmental biology ,biology.protein ,business - Abstract
Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.)
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- 2017
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3. From inflamm-aging to immune-paralysis: a slippery slope during aging for immune-adaptation
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Fulop, T., primary, Dupuis, G., additional, Baehl, S., additional, Le Page, A., additional, Bourgade, K., additional, Frost, E., additional, Witkowski, J. M., additional, Pawelec, G., additional, Larbi, A., additional, and Cunnane, S., additional
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- 2015
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4. Antiinflammatory therapy with canakinumab for atherosclerotic disease
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Ridker P.M., Everett B.M., Thuren T., MacFadyen J.G., Chang W.H., Ballantyne C., Fonseca F., Nicolau J., Koenig W., Anker S.D., Kastelein J.J.P., Cornel J.H., Pais P., Pella D., Genest J., Cifkova R., Lorenzatti A., Forster T., Kobalava Z., Vida-Simiti L., Flather M., Shimokawa H., Ogawa H., Dellborg M., Rossi P.R.F., Troquay R.P.T., Libby P., Glynn R.J., Krum H., Varigos J., Siostrzonek P., Sinnaeve P., Gotcheva N., Yong H., Urina-Triana M., Milicic D., Vettus R., Manolis A.J., Wyss F., Sigurdsson A., Fucili A., Veze I., Petrauskiene B., Salvador L., Klemsdal T.O., Medina F., Budaj A., Otasevic P., Lainscak M., Seung K.B., Commerford P., Donath M., Hwang J.J., Kultursay H., Bilazarian S., East C., Forgosh L., Harris B., Ligueros M., Bohula E., Charmarthi B., Cheng S., Chou S., Danik J., McMahon G., Maron B., Ning M., Olenchock B., Pande R., Perlstein T., Pradhan A., Rost N., Singhal A., Taqueti V., Wei N., Burris H., Cioffi A., Dalseg A.M., Ghosh N., Gralow J., Mayer T., Rugo H., Fowler V., Limaye A.P., Cosgrove S., Levine D., Lopes R., Scott J., Hilkert R., Tamesby G., Mickel C., Manning B., Woelcke J., Tan M., Manfreda S., Ponce T., Kam J., Saini R., Banker K., Salko T., Nandy P., Tawfik R., O’Neil G., Manne S., Jirvankar P., Lal S., Nema D., Jose J., Collins R., Bailey K., Blumenthal R., Colhoun H., Gersh B., Abreu M., Actis M.V., Aiub J., Aiub F., Albisu J., Alvarisqueta A., Avalos V., Barreto M., Berli M.A., Blumberg C., Bocanera M., Botta C., Bowen L., Budassi N., Buhlman S., Westberg J.C., Carabajal T., Caruso G., Casala J., Cendali G., Coloma G., Berra F.C., Cuneo C., Degennaro N., Dellasa M., Diaz M., Dos Santos P., Espinosa V., Facello A., Facello M., Farias E., Fernandez A.A., Ferrari V., Pacora F.F., Flores G.S., Franco M., Gabito A., Viola H.G., Garcia F., Garcia Duran R., Garcia Pinna J., Glenny J., Godoy Sanchez M., Grosse A., Guzman P., Hasbani E., Hominal M., Ibañez J., Jure H., Jure D., Vico M.L., Liniado G., Luciardi H., Luquez H., Maehara G., Maffei L., Majul C., Mallagray M., Marinaro S., Martinez J., Massaccesi R., De Los Milagros Had M., Azize G.M., Montana O., Montenegro E., Morell Y., Muntaner J., Navarrete S., Olmedo M., Paganini M., Paz S., Perez Manghi F., Piskorz D., Polato C., Recoaro R., Romano A., Salinger M., Sanchez A., Saravia M.A., Sarjanovich R., Scaro G., Schiavi L.B., Soler J., Tinnirello V., Tomassi A., Valle M., Vallejo M.A., Venturini C., Marcela Wenetz L.M., Yossen M., Zaidman C., Zalazar L., Zangroniz P., Amerena J., Brady L., Colquhoun D., Eccleston D., Ferreira-Jardim A., French J., Jayasinghe R., Mcintosh C., Ord M., Plotz M., Purnell P., Roberts-Thomson P., Schultz C., Shanahan T., Tan R., Taverner P., Turner F., Vibert J., Vorster M., William M., Youssef G., Bergler-Klein J., Brath H., Brodmann M., Fliesser-Goerzer E., Haider K., Heeren G., Hiden C., Mandic L., Paulweber B., Ploechl A., Prenner A., Steringer-Mascherbauer R., Strohner-Kaestenbauer H., Barbato E., Bouvy C., Briké C., Charlier F., Cools F., De Knijf K., De Wolf L., Delforge M., Deweerdt N., Gits F., Goffinet C., Hermans K., Hollanders G., Mestdagh I., Pirenne B., Servaes V., Simons N., Tahon S., Theunissen E., Van Genechten G., Vervoort G., Vissers C., Vranckx P., Vrolix M., Abib E.Jr., Abrantes J., Araujo Fonseca M., Barbosa E., Barroso W., Barroso A., Bodanese L., Botelho R., Costa Amorim R., Da Costa F., Da Silva A., Da Silva O.Jr., Da Silva D.Jr., Ferreira Dos Santos T., Dos Santos F., Dos Santos A., Duda N., Feitosa G., Felario Junior GA., Ferraz R., Filho P., Fonseca A., Wanderley F.F., Freitas E., Fucci F., Marengo Garcia De Carvalho L., Hernandez M., Hettwer Magedanz E., Julião K., Kormann A., Lameira A., Lima F., Lino E., Maia L., Manenti E., Marchi A.L., Fischer S.M., Michalaros Y., Moraes J.Jr., Moreira L., Pagnan M., Pesce F., Pinheiro L., Rassi S., Reis G., Reis H., Resende I., Roel A., Ruschel K., Saporito W., Saraiva J.F., Seroqui M., Silva R., Unterkircher B., Vicente C., Vieira N., Xavier 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Luz Serrano H., Sotomayor A., Urina M., Vesga B., Yupanqui H., Akrap B., Busic N., Ciglenecki N., Cmrecnjak J., Fucak E., Gabor M., Jeric M., Jutrisa N., Kordic K., Planinc I., Popovic Z., Radeljic V., Sesto I., Sutalo K., Tusek S., Belohlavek J., Budkova J., Busak L., Capova L., Cech V., Cermak O., Coufalova Z., Cyprian R., Dedek V., Dedkova S., Ferkl R., Hanak P., Hanustiakova A., Homza M., Horackova K., Houra M., Iveta H., Kaiserova L., Kala P., Karel I., Kellnerova I., Koleckar P., Kreckova M., Krupicka J., Lorenc Z., Machova V., Malik J., Masarikova L., Matyasek I., Mikus M., Mikusova T., Ondrasik J., Otava M., Palubova L., Pavlickova L., Peterka M., Petrova I., Pokorna B., Povolny P., Radvan M., Reznakova S., Rickova Z., Roszkowska P., Rotreklova M., Samkova D., Skalicka H., Slechticka A., Sternthal P., Telekes P., Tesak M., Vesely P., Vesely J., Vins P., Vitovec M., Vodnansky P., Zidova M., Keba E., Laane E., Pool T., Randvee L., Ratnik E., Reimand M., Reinmets S., Rivis L., Siemann M., Stern M., Toom M., Vahula V., Apel T., Axthelm C., Ayasse D., Ayasse M., Baar M., Baeumer A., Bagi E.S., Becker B., Binder A., Blankenberg S., Braun P., Johansen B.B., Contzen C., Delfonso F., Denecke C., Dengler T., Donaubauer T., Eichinger G., Englmann E., Erhard M., Faghih M., Foerster A., Frankenstein L., Fuchs R., Furch G., Gaeb-Strasas B., Germann H., Giese C., Goette A., Gravenhorst-Muenter U., Haege R., Haenel T., Hagemann D., Hagenow A., Hanefeld M., Heider J., Heisters J., Hennig D., Hielscher S., Himpel-Boenninghoff A., Holscher A., Hornig M., Jeserich M., Kaczmarek N., Kanitz S., Kara Y.D., Khariouzov A., Kiefer R., Kiroglu K., Klamm M., Klein C., Korth-Wiemann B., Krapivsky A., Kuenzler J., Kuntzsch A., Landers B., Lappo M., Laube S., Leggewie S., Lehmann D., Lepp H., Lierse T., Lindner C., Luecke-Uzar M., Luedemann J., Marschke T., Maruzzo S., Mauersberger K., Maus O., Meinrich M., Meissner A., Moehring B., Muehlhaus J., Mueller S., Muenter K.C., Muenzel T., 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A., Mantas I., Megalou A., Milkas A., Nanas J., Olympios C.D., Patsilinakos S., Perperis A., Poulimenos L., Saloustros I., Tsioufis K., Tsorbatzoglou K., Vardas P., Zarifis I., Aguilar M., Arango J.L., Borrayo N.A., Corona V., Guerrero A., Guzman I., Haase F., De Krumbach L., Montenegro P., Munoz R., Munoz N., Paniagua A., Solares A., Vogel M., Anita S., Blazsek Z., Decsi K., Fulop T., Hangyal T., Hegedus V., Kalina A., Karakai H., Katona A., Kiss R.G., Kovacs A., Laszlo Z., Lupkovics G., Medvegy M., Merkely B., Mihaly N., Nagy A.C., Dékány J.N., Nikoletta P., Noori E., Penzes J., Poor F., Sarszegi Z., Simay A., Simon J., Szakal I., Szatmarine V., Szocs A., Zilahi Z., Karsai X.Z., Andersen K., Sigurdadottir E., Skuladottir F., Abdullakutty J., Abhaichand R., Abhyankar A., Agarwal D.K., Aggarwal R.K., Ahire N., Awasthi A.K., Babu R., Bai A., Bali H.K., Banker D., Bhadade S., Bisne V., Bohra P., Raghu C., Chauhan D., Chauhan H., Chavada J., Chaware G., Chella S., Chintala P., Dash D., Desai D., Devasia T., Dhanak R., Dobariya H., Dudhatra N., Duhan S., Fulwani M., Ghondale N., Ghosh S., Gohel P., Govindaraj D., Goyal B., Goyal S., Gundala A.K., Gupta M., Hardas S., Iby M., Jagtap P., Jain A., Joshi U., Karpuram M., Kaur H., Khan A., Khan R., Kodem D.R., Koeitti P., Kulkarni L., Kullal P., Kumar K.S., Kumbla M., Latheef K., Lohkare M., Santosh M.J., Makhe B., Mandati M., Mehta A., Minocha G., Mittal A., Modi R., Mohan K., Oomman A., Pai R., Pai V., Palaniswami N., Pansheriya A., Parekh N., Patel J., Patel R., Patole T., Praveen M., Radhakrishnan V., Rajan B A., Rajasekhar D., Rao M., Rao M.B., Rao N.M., Rathnavel S., Rathore A., Rathore SRS., Rawat S., Reddy N.C., Sarma R., Sathe S., Shah J., Shaikh P., Sharma K., Sharma S., Sharma T., Shetty P., Sidhu G., Singh V., Sohi G.S., Srinath V.S., Raju S.S., Taran A., Thakkar B., Velusamy K., Vijan V., Vora V., Vuriya A.K., Agosta G.F., Antonicelli R., Ardissino D., Argiolas G., Baldin M.G., Benedetti G., Berti S., Bevilacqua M.T., Bolognesi M.G., Dessalvi C.C., Calabrese A., Campanale E.G., Candusso R., Caso P., Cosmi F., Crea F., Crocamo A., De Caterina R., De Rosa S., Destro M., Di Biase M., Dognini G.P., Eleuteri E., Fedele F., Ferrario M., Gabrielli D., Gamba C., Ganau A., Gravellone M., Iannopollo G., Indolfi C., Infusino F., Invitti C., Landolfi A., Lembo G., Liberato N.L., Mannucci E., Marino P., Mariottoni B., Marziali A., Mercuro G., Monti L., Mos L., Mureddu V., Musumeci M.B., Novo S., Panzarino C., Parente A., Perotti M., Filardi P.P., Petrillo C., Piatti P., Priori S., Racca V., Ragghianti B., Renda G., Righini V., Sarcone M., Senni M., Soro E., Tamburrini P., Vallone L., Villani G.Q., Volpe M., Ajioka M., Akai Y., Ashino K., Baden M., Doi M., Eki Y., Endo T., Fukuike C., Hagiwara Y., Hasegawa K., Higuchi Y., Higuchi T., Hioki M., Hirayama A., Hiroma J., Hosokawa S., Ichisawa M., Iijima T., Inada T., Inagaki M., Ito K., Kaigawa K., Kajihara S., Kamiya H., Kamiya J., Kaneno Y., Katahira K., Kataoka M., Kawai M., Kawasaki T., Kojima E., Komura Y., Kuramochi T., Kuruma T., Kyo E., Mani H., Miyamoto T., Morii I., Morinaga Y., Morisawa T., Nagai Y., Naka T., Nakamura Y., Nakamura S., Nakayoshi K., Nishibe A., Ogawa M., Okada Y., Okawa M., Sakamoto Y., Sakurada M., Sasaki S., Seki S., Shimomura H., Shinozaki T., Sugimoto N., Suzuki A., Taguchi S., Takahashi J., Takase S., Tanabe K., Tanaka A., Tani S., Tomioka J., Tsuboi H., Tsuji M., Tsujita K., Tsujiyama S., Umesu A., Yamada T., Yamaguchi E., Yamamoto H., Yamamoto T., Yamane M., Yanase T., Yasuoka S., Yasutake M., Yokoyama M., Yoshida M., Yoshimoto E., Yunoki C., Balode A., Dormidontova G., Flaksa I., Nagele-Luse I., Rancane G., Sime I., Bartuseviciene S., Cepinskiene L., Dobilas V., Grigaraviciene I., Marcinkeviciene J., Mazutavicius R., Miliuniene R., Motiejuniene R., Norkiene S., Norkute-Macijauske U., Rudys A., Slapikas R., Stonkute K., Strazdiene D., Tijuneliene E., Urbonas G., Vanagiene S., Viezelis M., Arenas Leon JL., Bayram E., Carrillo J., Davalos C., De Los Rios M., Delgadillo T., Hernández N., Leon S., Mendoza N., Muñoz W., Ramos G., Anneveldt A., Bakker H., Brouwer M., Bunschoten P., De Boer P., De Jong C., De Vos A., Den Hartog F., Doesborg L., Dommerholt R., Drost I., Ellenbroek D., Engelen W., Folkeringa R.J., Hamer BJB., Herrman J.P., Hoogslag PAM., Jansen M., Jerzewski A., Joosten C., Kalkman C., Kietselaer B., Kok M., Kooiman E., Kose V., Lardinois R., Lenderink T., Lok DJA., Lousberg A., Meijlis P., Mulder R., Singerling M., Smeele F., Stroes E., Swart H.P., Ten Holt W., Van Der Wal M., Van Der Zwaan C., Van Kempen W.W., Van Maarseveen M., Van Stein I., Viergever E.P., Visseren FLJ., Voors C., Nugteren SKZ., Ata B., Berulfsen A., Rønnevik T.D., Dickstein K., Furuseth B., Grundtvig M., Hansen H., Hofsoey K., Høivik H.O., Bøen R.H., Hurtig U., Pettersen K.I., Johansen E., Kleve R., Kolleroy C., Moen S., Nilsen V., Norin V., Otterstad J.E., Risberg K., Rønnevik P., Sirnes P.A., Skjelvan G., Strand S., Szacinski G., Vegsundvåg J., Alcalde J.M., Gomez Sanchez J., Rodriguez J., Rodriguez A., Zena N., Baszak J., Cymerman K., Czerski T., Fratczak M., Jaguszewska G., Kawka-Urbanek T., Koba M., Kopaczewski J., Kopczyńska M., Laniec M., Lysek R., Sciborski R., Szpajer M., Torun A., Wujkowski M., Zielinski M., Ahn Y., Baek C., Bang S.A., Chang K., Choi A.J., Han S., Hyun K., Kim M., Kim K.S., Kim B., Lee S.H., Lee J., Lee H.N., Lee J.H., Moon K., Park B., Park C., Tahk S., Yim K.H., Yim S., Tase T., Andor M., Aron G., Badea C., Casoinic F., Clocotan M., Coman S., Emil B., Imre B.S., Istratoaie O., Liviu C., Maximov D., Militaru C., Minescu B., Istvan K.P., Parepa I., Petrescu L., Podoleanu C., Pop C.F., Popa V., Popescu E., Radoi M., Sarbu I., Socoteanu E., Socoteanu G., Sorodoc L., Spiridon M., Stanciulescu G., Stefanescu M., Tanaseanu C., Tudoran M., Zdrenghea D., Agafina A., Akatova E., Avdonina N., Balukova E., Barbarash O.L., Bartosh L., Boyarkin M., Bulashova O., Burova N., Churina S., Demidova M., Dorogova I., Dovgalevskiy Y., Dovgolis S., Dudarev M., Fitilev S., Gapon L., Gazizianova V., Gordeev I., Ivanov I., Izmozherova N., Kazanskay E., Khirmanov V., Khromtsova O., Konradi A., Kosmacheva E., Kozlova S., Kulibaba E., Kuzin A., Libov I., Lipchenko A., Lozhkina N., Malchikova S., Morozov E., Myslyaeva L., Onuchina E., Palatkina T., Panov A., Parmon E., Petelina T., Repin A., Reznik I., Sazonova E., Sergienko T., Shaposhnik I., Shapovalova Y., Shustov S., Shvarts Y., Skopets I., Skuratova M., Smolenskaya O., Solovev O., Trofimov V., Vasiliev M., Vezikova N., Vozzhaev A., Yakushin S., Zadionchenko V., Apostolovic S., Adjic N.C., Ilic I., Ilic S., Nikolic L., Pupic L., Stokuca-Korac N., Antalik L., Bugan V., Csala L., Dokupilova A., Dzupina A., Forgon T., Fulop P., Gonsorcik J., Gyorgyova E., Holoubek D., Horvat P., Kamensky G., Kolikova V., Krupciakova B., Lenner E., Lennerova J., Lukac J., Majercak I., Mancikova I., Micko K., Nociar J., Pales J., Palka J.Jr., Poliacik P., Ruffini L., Sabo L., Skubova K., Slanina M., Smik R., Srdos V., Stitova M., Stofkova D., Strbova J., Such S., Toth P., Urgeova L., Vinanska D., Zareczky P., Flezar M., Kovacic D., Marcun R., Zagozen P., Bolsmann C., Conradie C., Dawood S.Y., Decsi K.L., Ebrahim I., Henley L., Horak A., Kapp I., Komati S., Lock E., Maboyi S., Makotoko E., Manga P., Page A., Ramdas S., Ranjith N., Roos J., Talliard C., Ajax K., Al-Khalili F., Assarsson E., Bergholtz T., Blom K.B., Boman K., Boström P.A., Curiac D., Jensen E.D., Dahlen G., Davidsson K., Duckert A., Hansson A., Härstedt N., Henriksson A., Olsson G.H., Johansson K., Jonsson J.E., Knutsson A., Lindholm C.J., Lönnberg I., Lundqvist M., Mellberg L., Moodh J., Mooe T., Olofsson M., Risenfors M., Rönndahl M., Sundelin R., Suorra I., Torgersruud M., Torstensson I., Chen C.P., Chen Z.C., Chen M.H., Cheng S.M., Cheng J.J., Fang C.Y., Ho C.J., Hsieh I.C., Huang P.H., Huang A., Kuo J.Y., Lai W.T., Lee S.C., Lin T., Liu H.M., Tsai M.C., Tsao H.M., Tzong L., Ueng K.C., Wang Y.L., Wang H.C., Wang C.P., Yang C.C., Abaci F., Birdane A., Yilmaz M.B., Asim Oktay AO., Kan G., Koldas N., Ozcan I.T., Sahin M., Sahin T., Saka B., Tekten T., Ucar N., Uresin S., Yigit Z., Arif I., Bakhai A., Baksi A., Blagdon M., Brickman T., Brown N., Burton M., Burton J., Chaggar S., Chung A., Collier D., Covell W., Crawford G., Davies N., Davies M., Dayer M., Doughty A., Duff J., Dwenger E., Fisher J., Fitzpatrick L., Garner K., Glover J., Haughton G., Ilsley M., Ivan P., Voyzey E.J., Keenan S., Kelt T., Knight J., Kondagunta V., Lang C., Lee K., Lim L., Macdonald J., Mathew A., Mckenzie A., Mckibbin A., Michalska A., Pagett K., Pogson A., Price R., Price D., Procter K., Pye M., Redfearn H., Rewbury J., Ryding A., Sattar N., Sharp A., Shaw P., Simpson H., Smith W., Squire I., Storey R., Teenan M., Thomas H., Townend J., Trevelyan J., Wakeling J., Walukiewicz P., Wilkinson S., Zaman A., Acevedo L., Benton J., 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W., Caballero-Valiente B., Carr K., Halliwell T.C., Castillo J., Cei L., Cerda L., Chambers J., Chamblee T., Chattin W., Chee L., Chen Y.C., Cherlin R., Cheung D., Chiodi L., Christensen L., Christenson S., Cislowski D., Clavier-Firmin C., Colfer H., Colvin T., Cosgrove N., Covert C., Cox B., Cox R., Craig W., Crandall L., Crepps K., Cromer M., Cruz H., Cruz M., Cucher F., Damron M., Dave K., Dave B., Davis M., Davis B., Dawkins-Hughes S., Dean J., Debnam S., Defosse C., Dehning M., Dela Llana A., Dellorso M., Denham D., Desalle D., Dettmer M., Dhawan M., Diago M., Dicken T., Diederich C., Diederich M., Diehl R., Digangi D., Diller P., Dimattia M., Dodds G., Doggett J., Donahue K., Doughty L., Dragutksy B., Dreese M., Dunhurst F., Dunn D., Dutka C., Earl J., Eaton C., Eaves W., Ebeling K., Eder F., Edgerton L., Edillo C., Edwards J., Edwards T., Einhorn D., El Hafi S., Ellis M., Erickson B., Ervin W., Eskridge L., Fail P., Falcon D., Fang C., Fattal P., Fawson A., Felix L., Ferdinand K., Fien E., Fintel D., Firek C., Fitz-Patrick D., Flores E., Flores H., Floro T., Forker A., Foster M., Foucauld J., Lehman K.F., Fox B., Francoeur L., Frandsen B., Frivold G., Fruchter G., Fullerton D., Gabriel J., Gacioch G., Garas S., Garcia N., Garcia Rinaldi R., Garcia-Fragoso V., Garcia-Portela M., Gelb R., George F., Ghali J., Gilbert J., Gilley J., Glancy R., Goff R., Goldberg N., Gonzales D., Gonzales V., Gonzalez E., Gorges R., Gould R., Grabeau R., Grable M., Graham J.A., Graif J., Green E., Greener R., Greenway F., Grieshaber V., Griffin S., Gros C., Gudipati RVC., Guillinta P., Gupta V., Gutmann J., Gwyn M., El Hachem M., Hage F., Hageman T., Haidar A., Hakas J., Haldis T., Hall L., Hall C., Hall S., Halpern S., Hamud-Socoro A., Hardee L., Harrell W., Harrington A., Hartwell J., Hasan F., Hattler B., Haught H., Haynes E., Haywood A., Heaney L., Hecht J., Hernandez I., Herzog W., Hess E., Hill H., Hilton T., Hinderaker P., Hodnett P., Hoffman M., Hogan C., Holmes Z., Rees D.H., Hotchkiss D., Huang P., Humbert J., Hutchens E., Iachini K., Ibarra M., Igbokidi O., Ilahi T., Imbrognio M., Ipp E., Iteld B., Jacques G., Jafri A., Jafry B., Jardula M., Jefferson D., Jenkins R., Johnson E., Johnson J., Jones S., Kawahara M., Kelehan S., Kelly R., Kendall T., Kereiakes D., Khan M., Khan S., Kick J., Kimmel M., King T., King A., Kirkland S., Kissel S., Kitchens D., Klein P., Klugherz B., Korban E., Koren M., Korte M., Kostis J., Kotek L., Kozak M., Kreutter F., Kusnick B., Labovitz R., Lail J., Lamance J., Lamas G., Lambert J., Lambert C., Landzberg J., Langdon J., Lavoie W., Ledger G., Lee T., Lehman R., Leimbach W., Lennard M., Lepor N., Lester F., Levin P., Levinson L., Lewis D., Lillo J., Link L., Long C., Longaker R., Lorch G., Lucksinger G., Lynd S., Rhudy J.M., Madder R., Magness K., Maheshwari A., Alan A., Malek M., Maletz L., Malhotra V., Malhotra S., Mandviwala M., Mani C.K., Manuel J., Marchelletta N., Marshall L., Marsters M., Martin L., Martinez E., 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Smith G., Smith B., Smith J., Soca Y., Sofley C., Sopko K., Sosa-Padilla M., Sotolongo R., Sprinkle B., Srivastava S., Starzec M., Steinhoff J., Stelly L., Stinson J., Stoddard M., Stoltz S., Stone B., Stover T., Strain J., Strugatsky S., Stys T., Suleman A., Sullivan P., Tamez W., Tandon N., Teltser M., Terry P.S., Terry K., Tessmar C., Thekkoott D., Thomas D., Thomas D.M., Thompson E., Thompson J., Thornton A., Tjaden T., Tobias C., Topper J., Tran A., Treasure C., Trenkamp P., Trevino M., Tsou L., Tuholske C., Uy W., Vahtel M., Vaid B., Valenzuela M., Vance A., Vandam J., Vanhecke T., Vanness WC III., Vargas R., Vaz S., Vazquez Tanus J., Veerina K., Vega J., Vento A., Vijay N., Voelker F., Vogt E., Vold D., Vora K., Wade R.D., Wadell C., Waksman R., Walker K., Wallace K., Warren M., Washam M., Watson B., Webel R., Wells T., West M., Whitaker J., White J., White C., White A., Wilhoit G., Wilkins M., Willingham K., Wilson S., Wilson V., Wise J., Woodall S., Woods A., Wright J., Xu 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Taqueti V., Wei N., Burris H., Cioffi A., Dalseg A.M., Ghosh N., Gralow J., Mayer T., Rugo H., Fowler V., Limaye A.P., Cosgrove S., Levine D., Lopes R., Scott J., Hilkert R., Tamesby G., Mickel C., Manning B., Woelcke J., Tan M., Manfreda S., Ponce T., Kam J., Saini R., Banker K., Salko T., Nandy P., Tawfik R., O’Neil G., Manne S., Jirvankar P., Lal S., Nema D., Jose J., Collins R., Bailey K., Blumenthal R., Colhoun H., Gersh B., Abreu M., Actis M.V., Aiub J., Aiub F., Albisu J., Alvarisqueta A., Avalos V., Barreto M., Berli M.A., Blumberg C., Bocanera M., Botta C., Bowen L., Budassi N., Buhlman S., Westberg J.C., Carabajal T., Caruso G., Casala J., Cendali G., Coloma G., Berra F.C., Cuneo C., Degennaro N., Dellasa M., Diaz M., Dos Santos P., Espinosa V., Facello A., Facello M., Farias E., Fernandez A.A., Ferrari V., Pacora F.F., Flores G.S., Franco M., Gabito A., Viola H.G., Garcia F., Garcia Duran R., Garcia Pinna J., Glenny J., Godoy Sanchez M., Grosse A., Guzman P., Hasbani E., 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A., Steringer-Mascherbauer R., Strohner-Kaestenbauer H., Barbato E., Bouvy C., Briké C., Charlier F., Cools F., De Knijf K., De Wolf L., Delforge M., Deweerdt N., Gits F., Goffinet C., Hermans K., Hollanders G., Mestdagh I., Pirenne B., Servaes V., Simons N., Tahon S., Theunissen E., Van Genechten G., Vervoort G., Vissers C., Vranckx P., Vrolix M., Abib E.Jr., Abrantes J., Araujo Fonseca M., Barbosa E., Barroso W., Barroso A., Bodanese L., Botelho R., Costa Amorim R., Da Costa F., Da Silva A., Da Silva O.Jr., Da Silva D.Jr., Ferreira Dos Santos T., Dos Santos F., Dos Santos A., Duda N., Feitosa G., Felario Junior GA., Ferraz R., Filho P., Fonseca A., Wanderley F.F., Freitas E., Fucci F., Marengo Garcia De Carvalho L., Hernandez M., Hettwer Magedanz E., Julião K., Kormann A., Lameira A., Lima F., Lino E., Maia L., Manenti E., Marchi A.L., Fischer S.M., Michalaros Y., Moraes J.Jr., Moreira L., Pagnan M., Pesce F., Pinheiro L., Rassi S., Reis G., Reis H., Resende I., Roel A., Ruschel K., 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Mehta S., Michaud N., Kouz S.M., Murphy G., OKeefe D., Otis R., Ouimet F., Pandey S., Peck C., Perkins L., Richert L., Robbins K., Robinson S., Cabau J.R., Ross B., Roy C., Roy M., Roy A., Rupka D., Affaki G.S., Saunders K., Savard D., Soucy D., St Amour E., Thiessen S., Vertes G., Vezina M., Vincelli G., Weisnagel S.J., Zadra R., Chen J., Chen Y., Dong X., Feng Y., Feng Z., Fu G., Han B., Hao Y., He Y., He Z., Hong T., Jia Z., Jiang T., Jiang J., Jiang X., Ke Y., Li Y., Li Z., Li W., Li X., Liu P., Liu Y., Liu B., Liu S., Liu L., Lu Z., Lv Y., Ma C., Ma G., Peng L., Qing L., Ren L., Sang X., Song M., Sun Z., Wang J., Wang Y., Wei J., Wu W., Wu J., Xu H., Yan J., Yang P., Yang K., Yao Z., Yaoqing H., Yuan Z., Zhai Z., Zhang J., Zhang Y., Zhao R., Zhou H., Accini Mendoza JL., Aparicio C.V., Castillo T., Chaverra I., Conrado Y., Coronel J., Cotes C., Cuentas I., Cuervo A., Dussan M.A., Echeverria L., Hernandez E., Ibarra J., Isaza D., Jimenez D., Lopez P., Manzur F., Mejia I., Mendoza Y., Molina D.I., Patino J.M., Rodriguez D., Rodriguez L.M., Rodriguez S.M., Sanchez Vallejo G., Luz Serrano H., Sotomayor A., Urina M., Vesga B., Yupanqui H., Akrap B., Busic N., Ciglenecki N., Cmrecnjak J., Fucak E., Gabor M., Jeric M., Jutrisa N., Kordic K., Planinc I., Popovic Z., Radeljic V., Sesto I., Sutalo K., Tusek S., Belohlavek J., Budkova J., Busak L., Capova L., Cech V., Cermak O., Coufalova Z., Cyprian R., Dedek V., Dedkova S., Ferkl R., Hanak P., Hanustiakova A., Homza M., Horackova K., Houra M., Iveta H., Kaiserova L., Kala P., Karel I., Kellnerova I., Koleckar P., Kreckova M., Krupicka J., Lorenc Z., Machova V., Malik J., Masarikova L., Matyasek I., Mikus M., Mikusova T., Ondrasik J., Otava M., Palubova L., Pavlickova L., Peterka M., Petrova I., Pokorna B., Povolny P., Radvan M., Reznakova S., Rickova Z., Roszkowska P., Rotreklova M., Samkova D., Skalicka H., Slechticka A., Sternthal P., Telekes P., Tesak M., Vesely P., Vesely J., Vins P., Vitovec M., Vodnansky P., Zidova M., Keba E., Laane E., Pool T., Randvee L., Ratnik E., Reimand M., Reinmets S., Rivis L., Siemann M., Stern M., Toom M., Vahula V., Apel T., Axthelm C., Ayasse D., Ayasse M., Baar M., Baeumer A., Bagi E.S., Becker B., Binder A., Blankenberg S., Braun P., Johansen B.B., Contzen C., Delfonso F., Denecke C., Dengler T., Donaubauer T., Eichinger G., Englmann E., Erhard M., Faghih M., Foerster A., Frankenstein L., Fuchs R., Furch G., Gaeb-Strasas B., Germann H., Giese C., Goette A., Gravenhorst-Muenter U., Haege R., Haenel T., Hagemann D., Hagenow A., Hanefeld M., Heider J., Heisters J., Hennig D., Hielscher S., Himpel-Boenninghoff A., Holscher A., Hornig M., Jeserich M., Kaczmarek N., Kanitz S., Kara Y.D., Khariouzov A., Kiefer R., Kiroglu K., Klamm M., Klein C., Korth-Wiemann B., Krapivsky A., Kuenzler J., Kuntzsch A., Landers B., Lappo M., Laube S., Leggewie S., Lehmann D., Lepp H., Lierse T., Lindner C., Luecke-Uzar M., Luedemann J., Marschke T., Maruzzo S., Mauersberger K., Maus O., Meinrich M., Meissner A., Moehring B., Muehlhaus J., Mueller S., Muenter K.C., Muenzel T., Naumann R., Nebel J., Neumann J., Nuding S., Overhoff U., Papke B., Pencz I., Peter Y., Peukert A.M., Radde I., Rau T., Regner S., Reichenbach D., Reimer D., Rinke A., Roettges R., Romanski A., Rummel R., Samer H., Sanuri M., Sarnighausen H.E., Schäfer B., Scheibner T., Schermaul K.H., Schindler A., Schlundt C., Schmidt E., Schmidt K., Schnabel A., Schoen N., Schorn K., Schroeder T., Schulenburg D., Schulz M., Schulze U., Schulze J., Schumacher M., Schwerin G., Schwerin M., Stadelmeier S., Stahl H.D., Stahl A., Stockhausen J., Stockhausen G., Stoessel J., Stolze K., Stratmann M., Szymanowski N., Teschner A.B., Teske A., Uecker C., Veit S., Voeller H., Walter I., Walter J., Walther I., Weber H.G., Weimer J., Wichterich K., Wiebusch A., Willmerdinger M., Willner C., Winkelmann B., Winkler J., Wistuba T., Woehrle J., Wohnlich T., Wolf S., Woyczak D., Wrage P., Zirlik A., Anadiotis A., Chachalis 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Raghu C., Chauhan D., Chauhan H., Chavada J., Chaware G., Chella S., Chintala P., Dash D., Desai D., Devasia T., Dhanak R., Dobariya H., Dudhatra N., Duhan S., Fulwani M., Ghondale N., Ghosh S., Gohel P., Govindaraj D., Goyal B., Goyal S., Gundala A.K., Gupta M., Hardas S., Iby M., Jagtap P., Jain A., Joshi U., Karpuram M., Kaur H., Khan A., Khan R., Kodem D.R., Koeitti P., Kulkarni L., Kullal P., Kumar K.S., Kumbla M., Latheef K., Lohkare M., Santosh M.J., Makhe B., Mandati M., Mehta A., Minocha G., Mittal A., Modi R., Mohan K., Oomman A., Pai R., Pai V., Palaniswami N., Pansheriya A., Parekh N., Patel J., Patel R., Patole T., Praveen M., Radhakrishnan V., Rajan B A., Rajasekhar D., Rao M., Rao M.B., Rao N.M., Rathnavel S., Rathore A., Rathore SRS., Rawat S., Reddy N.C., Sarma R., Sathe S., Shah J., Shaikh P., Sharma K., Sharma S., Sharma T., Shetty P., Sidhu G., Singh V., Sohi G.S., Srinath V.S., Raju S.S., Taran A., Thakkar B., Velusamy K., Vijan V., Vora V., Vuriya A.K., Agosta 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T., Inagaki M., Ito K., Kaigawa K., Kajihara S., Kamiya H., Kamiya J., Kaneno Y., Katahira K., Kataoka M., Kawai M., Kawasaki T., Kojima E., Komura Y., Kuramochi T., Kuruma T., Kyo E., Mani H., Miyamoto T., Morii I., Morinaga Y., Morisawa T., Nagai Y., Naka T., Nakamura Y., Nakamura S., Nakayoshi K., Nishibe A., Ogawa M., Okada Y., Okawa M., Sakamoto Y., Sakurada M., Sasaki S., Seki S., Shimomura H., Shinozaki T., Sugimoto N., Suzuki A., Taguchi S., Takahashi J., Takase S., Tanabe K., Tanaka A., Tani S., Tomioka J., Tsuboi H., Tsuji M., Tsujita K., Tsujiyama S., Umesu A., Yamada T., Yamaguchi E., Yamamoto H., Yamamoto T., Yamane M., Yanase T., Yasuoka S., Yasutake M., Yokoyama M., Yoshida M., Yoshimoto E., Yunoki C., Balode A., Dormidontova G., Flaksa I., Nagele-Luse I., Rancane G., Sime I., Bartuseviciene S., Cepinskiene L., Dobilas V., Grigaraviciene I., Marcinkeviciene J., Mazutavicius R., Miliuniene R., Motiejuniene R., Norkiene S., Norkute-Macijauske U., Rudys A., Slapikas R., 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Wakeling J., Walukiewicz P., Wilkinson S., Zaman A., Acevedo L., Benton J., Abbate A., Aboufakher R., Acampora M., Acampora D., Aceto L., Acevedo B., Acheatel R., Adams M., Adams A., Ahmad I., Ahmed S.H., Aish B., Akyea-Djamson A., Al Joundi T., Alcide P., Alfieri A., Alfonso T., Alfrey A., Allen J., Alllison D.C., Almaliky T., Amos A., Angiolillo D., Antolick A., Ara M., Aragorn L., Arevalo S., Armas E., Arthur A., Asafu-Adjaye N., Ashcom T., Ashford M., Aslam A., Ather N., Atieh M., Aull L., Ayala M., Azizad M., Backer T., Baehl S., Bailey S., Bair S., Baker C., Ballmajo M., Pieretti H.B., Baquero A., Barnett S., Baron S., Bartkowiak A., Bashir K., Beall K., Beauregard L.A., Sarah S., Beckett L., Belejchak P., Bendelow T., Bender D., Benjamin S., Berdoff R., Berger V., Bergeron P., Berk M., Bernstein M., Binns Y., Bitzer V., Blahey M., Bloch S., Bluemel J., Boffetti P., Boley K., Bonner J., Boudreaux R., Boulanger K., Bradley A., Bramlet D., Bredlau C., Briggs S., Brousalis L., Brown S., Brown C., Buchannan C., Burke W., Burley T., Burton C., Burtt D., Byars W., Caballero-Valiente B., Carr K., Halliwell T.C., Castillo J., Cei L., Cerda L., Chambers J., Chamblee T., Chattin W., Chee L., Chen Y.C., Cherlin R., Cheung D., Chiodi L., Christensen L., Christenson S., Cislowski D., Clavier-Firmin C., Colfer H., Colvin T., Cosgrove N., Covert C., Cox B., Cox R., Craig W., Crandall L., Crepps K., Cromer M., Cruz H., Cruz M., Cucher F., Damron M., Dave K., Dave B., Davis M., Davis B., Dawkins-Hughes S., Dean J., Debnam S., Defosse C., Dehning M., Dela Llana A., Dellorso M., Denham D., Desalle D., Dettmer M., Dhawan M., Diago M., Dicken T., Diederich C., Diederich M., Diehl R., Digangi D., Diller P., Dimattia M., Dodds G., Doggett J., Donahue K., Doughty L., Dragutksy B., Dreese M., Dunhurst F., Dunn D., Dutka C., Earl J., Eaton C., Eaves W., Ebeling K., Eder F., Edgerton L., Edillo C., Edwards J., Edwards T., Einhorn D., El Hafi S., Ellis M., Erickson B., Ervin W., Eskridge 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Willingham K., Wilson S., Wilson V., Wise J., Woodall S., Woods A., Wright J., Xu Z.J., Yarows S., Young A., Younis L., Zarate J., Zebrack J., Zhang W., Zieve F., and Zineldine A.
- Abstract
BACKGROUND: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. METHODS: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83
5. Predictors of the antibody response to influenza vaccination in older adults with type 2 diabetes.
- Author
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McElhaney JE, Garneau H, Camous X, Dupuis G, Pawelec G, Baehl S, Tessier D, Frost EH, Frasca D, Larbi A, and Fulop T
- Abstract
Objective: Type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic inflammatory diseases of the elderly. Its development is related to the alteration of the immune system with aging characterized by immunosenescence and inflamm-aging. In turn, T2DM also alters the immune response. As a consequence, older people with T2DM are more susceptible to influenza and to its complications as compared with healthy controls. Vaccination against influenza has shown poor efficacy in the older population and even less efficacy in patients with diabetes. We studied here the antibody response to vaccination in healthy and diabetic elderly participants., Research Design and Methods: In 2 groups of elderly participants (healthy N=119 and T2DM N=102), we measured the immunogenicity of influenza vaccine by hemagglutination inhibition assays. We assessed several blood and functional parameters as potential predictors of the vaccine efficacy., Results: We found no difference between antibody responses in diabetic elderly compared with healthy elderly. Among the biological and functional determinants, the cytomegalovirus (CMV) serostatus played a more prominent role in determining the magnitude of response. We concluded that in addition to age and diabetic status, immunological history such as CMV status should be taken into account. None of the other biological or functional parameters studied could be reliably linked to the vaccine antibody response in older adults who are not frail including those with well-controlled diabetes., Conclusions: Our data strongly suggest that influenza vaccine should be administered to elderly patients with T2DM; however, the immune determinants of the antibody response to influenza vaccination should be further investigated.
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- 2015
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6. Frailty, Inflammation and Immunosenescence.
- Author
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Fulop T, McElhaney J, Pawelec G, Cohen AA, Morais JA, Dupuis G, Baehl S, Camous X, Witkowski JM, and Larbi A
- Subjects
- Aged, Aged, 80 and over, Canada, Chronic Disease, Disease Susceptibility epidemiology, Disease Susceptibility physiopathology, Female, Geriatric Assessment methods, Humans, Immunosenescence immunology, Incidence, Inflammation epidemiology, Inflammation immunology, Male, Prognosis, Risk Assessment, Aging immunology, Aging physiology, Disease Susceptibility immunology, Frail Elderly, Immunosenescence physiology, Inflammation physiopathology
- Abstract
Frailty is a still-evolving concept of a complex phenomenon. There are several algorithms and strategies for assessing frailty syndrome, but currently, no universally accepted definition or measurement protocol has been determined. Consequently, the biological cause(s) of frailty are also poorly defined. Much circumstantial experimental data point to the dysregulation of several key physiological systems, including the neuroendocrine, musculoskeletal, metabolic and immune/inflammatory systems, resulting from alterations in functional reserves. Immune dysregulation and inflammation as causes of frailty have gained some support from the results of longitudinal studies, but a true causal relationship has not been established. This chapter will describe the immune/inflammatory alterations found in frailty and their putative causal relationships with this state., (2015 S. Karger AG, Basel.)
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- 2015
- Full Text
- View/download PDF
7. Aging, immunosenescence and membrane rafts: the lipid connection.
- Author
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Fulop T, Le Page A, Garneau H, Azimi N, Baehl S, Dupuis G, Pawelec G, and Larbi A
- Abstract
The decreased efficiency of immune responses in older people is partly a consequence of alterations in T lymphocyte functions caused by modifications in the early events of signal transduction. Several alterations in the signaling pathways of T lymphocytes have been described in older humans and animals. A unifying cause could be modifications in the physicochemical properties of the plasma membrane resulting from changes in its lipid composition and the distribution and function of lipid rafts (LR). The latter serve to assemble the initial components of the signaling cascade. Accumulating data suggest that the function of plasma membrane LR is altered with aging; we hypothesize that this would significantly contribute to immune dysregulation. The role of aging and cholesterol in LR functions in T lymphocytes is reviewed and discussed here.
- Published
- 2012
- Full Text
- View/download PDF
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