1,720,997 research outputs found

    Hereditary and acquired protein S deficiencies are associated with low TFPI levels in plasma.

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    J Thromb Haemost. 2010 Feb;8(2):294-300. Epub 2009 Nov 30. Hereditary and acquired protein S deficiencies are associated with low TFPI levels in plasma. Castoldi E, Simioni P, Tormene D, Rosing J, Hackeng TM. Department of Biochemistry, CARIM, Maastricht University, Maastricht, the Netherlands. [email protected] BACKGROUND: Protein S and tissue factor pathway inhibitor (TFPI) act together in down-regulating coagulation. OBJECTIVE: To investigate the TFPI/protein S system in hereditary and acquired protein S deficiency. METHODS: Plasma antigen levels of protein S and full-length TFPI were determined in heterozygous type I protein S-deficient individuals (n=35), patients on oral anticoagulant treatment (OAT) (n=29), oral contraceptive (OC) users (n=10) and matched controls. Thrombin generation was determined using calibrated automated thrombography. RESULTS: Full-length TFPI levels were lower in type I protein S-deficient individuals (76.8+/-33.8%) than in age- and sex-matched controls (128.0+/-59.4%, P<0.001). Among protein S-deficient individuals with thrombosis, those on OAT had not only lower total protein S levels (25.7+/-8.2% vs. 54.7+/-8.2%, P<0.001), but also lower full-length TFPI levels (52.6+/-15.0% vs. 75.4+/-22.9%, P=0.009) than those not on OAT. Similarly, OC users had lower protein S (73.8+/-11.5% vs. 87.9+/-10.8%, P=0.005) and full-length TFPI levels (73.7+/-27.7% vs. 106.4+/-29.2%, P=0.007) than non-users. When triggered with tissue factor, plasma from protein S-deficient individuals generated 3-5-fold more thrombin than control plasma. The difference was only partially corrected by normalization of the protein S level, full correction requiring additional normalization of the TFPI level. Protein S-immunodepletion experiments indicated that free protein S and full-length TFPI form a complex in plasma, and the protein S/TFPI interaction was confirmed by surface plasmon resonance analysis. CONCLUSIONS: Full-length TFPI binds to protein S in plasma and is reduced in genetic and acquired protein S deficiency. The concomitant TFPI deficiency substantially contributes to the hypercoagulable state associated with protein S deficiency. PMID: 20002538 [PubMed - indexed for MEDLINE

    Similar hypercoagulable state and thrombosis risk in type I and type III proteinS-deficient individuals from mixed type I/III families.

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    Haematologica. 2010 Sep;95(9):1563-71. Epub 2010 Apr 26. Similar hypercoagulable state and thrombosis risk in type I and type III protein S-deficient individuals from families with mixed type I/III protein S deficiency. Castoldi E, Maurissen LF, Tormene D, Spiezia L, Gavasso S, Radu C, Hackeng TM, Rosing J, Simioni P. Department of Biochemistry, Maastricht University P.O. Box 616, 6200 Maastricht, The Netherlands. [email protected] BACKGROUND: Protein S, which circulates in plasma in both free and bound forms, is an anticoagulant protein that stimulates activated protein C and tissue factor pathway inhibitor. Hereditary type I protein S deficiency (low total and low free protein S) is a well-established risk factor for venous thrombosis, whereas the thrombosis risk associated with type III deficiency (normal total and low free protein S) has been questioned. DESIGN AND METHODS: Kaplan-Meier analysis was performed on 242 individuals from 30 families with protein S deficiency. Subjects were classified as normal, or having type I or type III deficiency according to their total and free protein S levels. Genetic and functional studies were performed in 23 families (132 individuals). RESULTS: Thrombosis-free survival was not different between type I and type III protein S-deficient individuals. Type III deficient individuals were older and had higher protein S, tissue factor pathway inhibitor and prothrombin levels than type I deficient individuals. Thrombin generation assays sensitive to the activated protein C- and tissue factor pathway inhibitor-cofactor activities of protein S revealed similar hypercoagulable states in type I and type III protein S-deficient plasma. Twelve PROS1 mutations and two large deletions were identified in the genetically characterized families. CONCLUSIONS: Not only type I, but also type III protein S deficiency is associated with a hypercoagulable state and increased risk of thrombosis. These findings may, however, be restricted to type III deficient individuals from families with mixed type I/III protein S deficiency, as these represented 80% of type III deficient individuals in our cohort. PMCID: PMC2930959 PMID: 20421270 [PubMed - in process

    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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