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Secretory Phospholi...
Secretory Phospholipase A(2)-IIA and Cardiovascular Disease
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- Holmes, Michael V. (author)
- UCL, England
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- Simon, Tabassome (author)
- Hop St Antoine, France
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- J Exeter, Holly (author)
- UCL, England
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show more...
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- Folkersen, Lasse (author)
- Karolinska Institute, Sweden
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- Asselbergs, Folkert W. (author)
- University of Medical Centre Utrecht, Netherlands
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- Guardiola, Montse (author)
- University of Rovira and Virgili, Spain
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- Cooper, Jackie A. (author)
- UCL, England
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- Palmen, Jutta (author)
- UCL, England
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- Hubacek, Jaroslav A. (author)
- Institute Clin and Expt Med, Czech Republic
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- Carruthers, Kathryn F. (author)
- University of Edinburgh, Scotland
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- Horne, Benjamin D. (author)
- Intermt Medical Centre, UT USA
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- Brunisholz, Kimberly D. (author)
- Intermt Medical Centre, UT USA
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- Mega, Jessica L. (author)
- Brigham and Womens Hospital, MA USA
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- Van Iperen, Erik P A (author)
- Durrer Centre Cardiogenet Research, Netherlands
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- Li, Mingyao (author)
- University of Penn School Med, PA USA
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- Leusink, Maarten (author)
- University of Utrecht, Netherlands
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- Trompet, Stella (author)
- Leiden University of Medical Centre, Netherlands
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- Verschuren, Jeffrey J W. (author)
- Leiden University of Medical Centre, Netherlands
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- Kees Hovingh, G (author)
- University of Amsterdam, Netherlands
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- Dehghan, Abbas (author)
- Erasmus MC, Netherlands
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- Nelson, Christopher P. (author)
- University of Leicester, England
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- Kotti, Salma (author)
- Hop St Antoine, France
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- Danchin, Nicolas (author)
- University of Ulm, Germany
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- Scholz, Markus (author)
- University of Leipzig, Germany
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- Haase L., Christiane (author)
- Copenhagen University Hospital, Denmark
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- Rothenbacher, Dietrich (author)
- University of Ulm, Germany
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- Swerdlow, Daniel I. (author)
- UCL, England
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- Kuchenbaecker, Karoline B. (author)
- University of Cambridge, England
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- Staines-Urias, Eleonora (author)
- London School Hyg and Trop Med, England
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- Goel, Anuj (author)
- University of Oxford, England
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- van t Hooft, Ferdinand (author)
- Karolinska Institute, Sweden
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- Gertow, Karl (author)
- Karolinska Institute, Sweden
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- de Faire, Ulf (author)
- Karolinska Institute, Sweden
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- Panayiotou, Andrie G. (author)
- Cyprus Cardiovasc Educ and Research Trust, Cyprus
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- Tremoli, Elena (author)
- University of Milan, Italy
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- Baldassarre, Damiano (author)
- University of Milan, Italy
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- Veglia, Fabrizio (author)
- IRCCS, Italy
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- Holdt, Lesca M. (author)
- University of Leipzig, Germany
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- Beutner, Frank (author)
- University of Leipzig, Germany
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- Gansevoort, Ron T. (author)
- University of Groningen, Netherlands
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- Navis, Gerjan J. (author)
- University of Groningen, Netherlands
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- Mateo Leach, Irene (author)
- University of Groningen, Netherlands
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- Breitling, Lutz P. (author)
- German Cancer Research Centre, Germany
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- Brenner, Hermann (author)
- German Cancer Research Centre, Germany
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- Thiery, Joachim (author)
- University of Leipzig, Germany
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- Dallmeier, Dhayana (author)
- University of Ulm Medical Centre, Germany
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- Franco-Cereceda, Anders (author)
- Karolinska Institute, Sweden
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- Boer, Jolanda M A. (author)
- National Institute Public Health and Environm, Netherlands
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- Stephens, Jeffrey W. (author)
- Swansea University, Wales
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- Hofker, Marten H. (author)
- University of Groningen, Netherlands
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- Tedgui, Alain (author)
- INSERM, France
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- Hofman, Albert (author)
- Erasmus MC, Netherlands
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- Uitterlinden, Andre G. (author)
- Erasmus MC, Netherlands
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- Adamkova, Vera (author)
- Institute Clin and Expt Med, Czech Republic
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- Pitha, Jan (author)
- Institute Clin and Expt Med, Czech Republic
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- Onland-Moret, Charlotte N. (author)
- University of Medical Centre Utrecht, Netherlands
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- Cramer, Maarten J. (author)
- University of Medical Centre Utrecht, Netherlands
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- Nathoe, Hendrik M. (author)
- University of Medical Centre Utrecht, Netherlands
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- Spiering, Wilko (author)
- University of Medical Centre Utrecht, Netherlands
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- Klungel, Olaf H. (author)
- University of Utrecht, Netherlands
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- Kumari, Meena (author)
- UCL, England
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- Whincup, Peter H. (author)
- University of London, England
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- Morrow, David A. (author)
- Brigham and Womens Hospital, MA USA
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- Braund, Peter S. (author)
- University of Leicester, England
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- Hall, Alistair S. (author)
- University of Leeds, England
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- Olsson, Anders G. (author)
- Östergötlands Läns Landsting,Linköpings universitet,Avdelningen för kardiovaskulär medicin,Hälsouniversitetet,Endokrinmedicinska kliniken,Stockholm Heart Centre, Sweden
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- Doevendans, Pieter A. (author)
- University of Medical Centre Utrecht, Netherlands
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- Trip, Mieke D. (author)
- University of Amsterdam, Netherlands
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- Tobin, Martin D. (author)
- University of Leicester, England
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- Hamsten, Anders (author)
- Karolinska Institute, Sweden
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- Watkins, Hugh (author)
- University of Oxford, England
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- Koenig, Wolfgang (author)
- University of Ulm Medical Centre, Germany
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- Nicolaides, Andrew N. (author)
- University of London Imperial Coll Science Technology and Med, England
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- Teupser, Daniel (author)
- University of Leipzig, Germany
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- Day, Ian N M (author)
- Hop St Antoine, France
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- F Carlquist, John (author)
- Intermt Medical Centre, UT USA
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- Gaunt, Tom R. (author)
- University of Bristol, England
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- Ford, Ian (author)
- University of Glasgow, Scotland
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- Sattar, Naveed (author)
- University of Glasgow, Scotland
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- Tsimikas, Sotirios (author)
- University of Calif San Diego, CA USA
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- Schwartz, Gregory G. (author)
- VA Medical Centre, CO USA
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- Lawlor, Debbie A. (author)
- University of Bristol, England
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- Morris, Richard W. (author)
- UCL, England
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- Sandhu, Manjinder S. (author)
- VA Medical Centre, CO USA
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- Poledne, Rudolf (author)
- Institute Clin and Expt Med, Czech Republic
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- Maitland-van der Zee, Anke H. (author)
- University of Utrecht, Netherlands
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- Khaw, Kay-Tee (author)
- University of Cambridge, England
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- Keating, Brendan J. (author)
- Childrens Hospital Philadelphia, PA USA
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- van der Harst, Pim (author)
- University of Groningen, Netherlands
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- Price, Jackie F. (author)
- University of Edinburgh, Scotland
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- Mehta, Shamir R. (author)
- McMaster University, Canada
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- Yusuf, Salim (author)
- McMaster University, Canada
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- Witteman, Jaqueline C M (author)
- Erasmus MC, Netherlands
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- Franco, Oscar H. (author)
- Erasmus MC, Netherlands
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- Jukema, Wouter J. (author)
- Durrer Centre Cardiogenet Research, Netherlands
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- de Knijff, Peter (author)
- Leiden University of Medical Centre, Netherlands
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- Tybjaerg-Hansen, Anne (author)
- Copenhagen University Hospital, Denmark
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- Rader, Daniel J. (author)
- Penn Heart and Vasc Centre, PA USA
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- Farrall, Martin (author)
- University of Oxford, England
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- Samani, Nilesh J. (author)
- University of Leicester, England
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- Kivimaki, Mika (author)
- UCL, England
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- Fox, Keith A A. (author)
- University of Edinburgh, Scotland
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- Humphries, Steve E. (author)
- UCL, England
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- Anderson, Jeffrey L. (author)
- Intermt Medical Centre, UT USA
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- Boekholdt, Matthijs S. (author)
- University of Amsterdam, Netherlands
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- Palmer, Tom M. (author)
- University of Warwick, England
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- Eriksson, Per (author)
- Karolinska Institute, Sweden
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- Pare, Guillaume (author)
- McMaster University, Canada
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- Hingorani, Aroon D. (author)
- UCL, England
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- Sabatine, Marc S. (author)
- Brigham and Womens Hospital, MA USA
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- Mallat, Ziad (author)
- INSERM, France
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- Casas, Juan P. (author)
- UCL, England
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- Talmud, Philippa J. (author)
- UCL, England
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(creator_code:org_t)
- Elsevier, 2013
- 2013
- English.
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In: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 62:21, s. 1966-1976
- Related links:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Objectives This study sought to investigate the role of secretory phospholipase A(2) (sPLA(2))-IIA in cardiovascular disease. less thanbrgreater than less thanbrgreater thanBackground Higher circulating levels of sPLA(2)-IIA mass or sPLA(2) enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA(2) inhibitor (varespladib) was stopped prematurely for lack of efficacy. less thanbrgreater than less thanbrgreater thanMethods We conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA(2)-IIA isoenzyme, as an instrumental variable. less thanbrgreater than less thanbrgreater thanResults PLA2G2A rs11573156 C allele associated with lower circulating sPLA(2)-IIA mass (38% to 44%) and sPLA(2) enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA(2)-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA2 enzyme activity and MVE. less thanbrgreater than less thanbrgreater thanConclusions Reducing sPLA(2)-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events.
Keyword
- cardiovascular diseases
- drug development
- epidemiology
- genetics
- Mendelian randomization
- TECHNOLOGY
- TEKNIKVETENSKAP
Publication and Content Type
- ref (subject category)
- art (subject category)
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Holmes, Michael ...
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Simon, Tabassome
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J Exeter, Holly
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Folkersen, Lasse
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Asselbergs, Folk ...
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Guardiola, Monts ...
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show more...
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Cooper, Jackie A ...
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Palmen, Jutta
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Hubacek, Jarosla ...
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Carruthers, Kath ...
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Horne, Benjamin ...
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Brunisholz, Kimb ...
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Mega, Jessica L.
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Van Iperen, Erik ...
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Li, Mingyao
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Leusink, Maarten
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Trompet, Stella
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Verschuren, Jeff ...
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Kees Hovingh, G
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Dehghan, Abbas
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Nelson, Christop ...
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Kotti, Salma
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Danchin, Nicolas
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Scholz, Markus
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Haase L., Christ ...
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Rothenbacher, Di ...
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Swerdlow, Daniel ...
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Kuchenbaecker, K ...
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Staines-Urias, E ...
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Goel, Anuj
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van t Hooft, Fer ...
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Gertow, Karl
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de Faire, Ulf
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Panayiotou, Andr ...
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Tremoli, Elena
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Baldassarre, Dam ...
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Veglia, Fabrizio
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Holdt, Lesca M.
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Beutner, Frank
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Gansevoort, Ron ...
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Navis, Gerjan J.
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Mateo Leach, Ire ...
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Breitling, Lutz ...
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Brenner, Hermann
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Thiery, Joachim
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Dallmeier, Dhaya ...
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Franco-Cereceda, ...
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Boer, Jolanda M ...
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Stephens, Jeffre ...
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Hofker, Marten H ...
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Tedgui, Alain
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Hofman, Albert
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Uitterlinden, An ...
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Adamkova, Vera
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Pitha, Jan
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Onland-Moret, Ch ...
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Cramer, Maarten ...
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Nathoe, Hendrik ...
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Spiering, Wilko
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Klungel, Olaf H.
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Kumari, Meena
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Whincup, Peter H ...
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Morrow, David A.
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Braund, Peter S.
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Hall, Alistair S ...
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Olsson, Anders G ...
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Doevendans, Piet ...
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Trip, Mieke D.
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Tobin, Martin D.
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Hamsten, Anders
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Watkins, Hugh
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Koenig, Wolfgang
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Nicolaides, Andr ...
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Teupser, Daniel
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Day, Ian N M
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F Carlquist, Joh ...
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Gaunt, Tom R.
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Ford, Ian
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Sattar, Naveed
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Tsimikas, Sotiri ...
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Schwartz, Gregor ...
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Lawlor, Debbie A ...
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Morris, Richard ...
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Sandhu, Manjinde ...
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Poledne, Rudolf
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Maitland-van der ...
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Khaw, Kay-Tee
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Keating, Brendan ...
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van der Harst, P ...
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Price, Jackie F.
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Mehta, Shamir R.
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Yusuf, Salim
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Witteman, Jaquel ...
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Franco, Oscar H.
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Jukema, Wouter J ...
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de Knijff, Peter
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Tybjaerg-Hansen, ...
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Rader, Daniel J.
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Farrall, Martin
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Samani, Nilesh J ...
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Kivimaki, Mika
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Fox, Keith A A.
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Humphries, Steve ...
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Anderson, Jeffre ...
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Boekholdt, Matth ...
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Palmer, Tom M.
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Eriksson, Per
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Pare, Guillaume
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Hingorani, Aroon ...
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Sabatine, Marc S ...
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Mallat, Ziad
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Casas, Juan P.
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Talmud, Philippa ...
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