1,720,973 research outputs found

    Apolipoprotein proteomics for residual lipid-related risk in coronary heart disease

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    Background: Recognition of the importance of conventional lipid measures and the advent of novel lipid-lowering medications have prompted the need for more comprehensive lipid panels to guide use of emerging treatments for the prevention of coronary heart disease (CHD). This report assessed the relevance of 13 apolipoproteins measured using a single mass-spectrometry assay for risk of CHD in the PROCARDIS case-control study of CHD (941 cases/975 controls). Methods: The associations of apolipoproteins with CHD were assessed after adjustment for established risk factors and correction for statin use. Apolipoproteins were grouped into 4 lipid-related classes [lipoprotein(a), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides] and their associations with CHD were adjusted for established CHD risk factors and conventional lipids. Analyses of these apolipoproteins in a subset of the ASCOT trial (Anglo-Scandinavian Cardiac Outcomes Trial) were used to assess their within-person variability and to estimate a correction for statin use. The findings in the PROCARDIS study were compared with those for incident cardiovascular disease in the Bruneck prospective study (n=688), including new measurements of Apo(a). Results: Triglyceride-carrying apolipoproteins (ApoC1, ApoC3, and ApoE) were most strongly associated with the risk of CHD (2- to 3-fold higher odds ratios for top versus bottom quintile) independent of conventional lipid measures. Likewise, ApoB was independently associated with a 2-fold higher odds ratios of CHD. Lipoprotein(a) was measured using peptides from the Apo(a)-kringle repeat and Apo(a)-constant regions, but neither of these associations differed from the association with conventionally measured lipoprotein(a). Among HDL-related apolipoproteins, ApoA4 and ApoM were inversely related to CHD, independent of conventional lipid measures. The disease associations with all apolipoproteins were directionally consistent in the PROCARDIS and Bruneck studies, with the exception of ApoM. Conclusions: Apolipoproteins were associated with CHD independent of conventional risk factors and lipids, suggesting apolipoproteins could help to identify patients with residual lipid-related risk and guide personalized approaches to CHD risk reduction

    Proteomic profiling identifies novel independent relationships between inflammatory proteins and myocardial infarction

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    Background Inflammation has been implicated in the pathogenesis of coronary heart disease, but the relevance and independence of individual inflammatory proteins is uncertain. Objective To examine the relationships between a spectrum of inflammatory proteins and myocardial infarction (MI). Methods and results A panel of 92 inflammatory proteins was assessed using an OLINK multiplex immunoassay among 432 MI cases (diagnosed < 66 years) and 323 controls. Logistic regression was used to estimate associations between individual proteins and MI, after adjustment for established cardiovascular risk factors and medication use, and stepwise regression to identify proteins with independent effects. Machine learning techniques (Boruta analysis and LASSO regression) and bioinformatic resources were used to examine the concordance of results with those obtained by conventional methods and explore the underlying biological processes to inform the validity of the associations. Among the 92 proteins studied, 62 (67%) had plasma concentrations above the lower limit of detection in at least 50% of samples. Of these, 15 individual proteins were significantly associated with MI after covariate adjustment and correction for multiple testing. Five of these 15 proteins (CDCP1, CD6, IL1–8R1, IL-6, and CXCL1) were independently associated with MI, with up to three-fold higher risks of MI per doubling in plasma concentrations. Findings were further validated using machine learning techniques and biologically focused analyses. Conclusions This study, demonstrating independent relationships between five inflammatory proteins and MI, provides important novel insights into the inflammatory hypothesis of MI and the potential utility of proteomic analyses in precision medicine

    A trio family study showing association of the lymphotoxin-alpha N26 (804A) allele with coronary artery disease.

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    Family-based studies to map susceptibility genes through linkage disequilibrium have been successful in early-onset diseases where parental-proband trios are readily collected, but are believed to be unworkable for late-onset diseases such as coronary artery disease (CAD). PROCARDIS is a European multicentre study that was designed to identify susceptibility genes for CAD. We have tested the transmission of a putatively functional allele, lymphotoxin-alpha N26 (804A), in more than 400 PROCARDIS trio families. The present study demonstrates association of this allele with CAD in white Europeans, a different ethnic group with a heavier CAD burden than the Japanese in which the association was initially identified, which suggests a broad relevance to CAD susceptibility. The practicalities of implementing a trio-family design for late-onset diseases are discussed

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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