823 research outputs found
A novel role for CD36 in VLDL-enhanced platelet activation
No full textType 2 diabetes is characterized by increased plasma triglyceride levels and a fourfold increase in ischemic heart disease, but the mechanism is unclear. CD36 is a receptor/transporter that binds fatty acids of lipoproteins. CD36 deficiency has been linked with insulin resistance. There is strong evidence of in vivo interaction between platelets and atherogenic lipoproteins suggesting that atherogenic triglyceride-rich lipoproteins, such as VLDL, that are increased in diabetic dyslipidemia are important in this process. This study demonstrates that VLDL binds to the platelet receptor CD36, enhances platelet thromboxane A2 production, and causes increased collagen-mediated platelet aggregation. VLDL enhanced collagen-induced platelet aggregation by 1) shortening the time taken for aggregation to begin (lag time) to 70% of control (P = 0.001); 2) increasing maximum aggregation to 170% of control (P = 0.008); and 3) increasing thromboxane production to 3,318% of control (P = 0.004), where control represents platelets stimulated with collagen (100%). A monoclonal antibody against CD36 attenuated VLDL-enhanced collagen-induced platelet aggregation by 1) inhibiting binding of VLDL to platelets by 75% (P = 0.041); 2) lengthening lag time to 190% (P < 0.001); and 3) decreasing thromboxane production to 8% of control (P < 0.001). In support of this finding, platelets from Cd36-deficient rats showed no increase in aggregation, thromboxane production, and VLDL binding in contrast to platelets from rats expressing CD36. These data suggest that platelet Cd36 has a key role in VLDL-induced collagen-mediated platelet aggregation, possibly contributing to atherothrombosis associated with increased VLDL levels
Risk of recurrence after venous thromboembolism in men and women : patient level meta-analysis
No full textObjective: To determine the effect of sex on the risk of recurrent venous thromboembolism in all patients and in patients with venous thromboembolism that was unprovoked or provoked (by non-hormonal factors). Data source: Comprehensive search of electronic databases (Medline, Embase, CINAHL, Cochrane Central Register of Controlled Trials) until July 2010, supplemented by review of conference abstracts and contact with content experts. Study selection: Seven prospective studies investigating an association between D-dimer, measured after anticoagulation was stopped, and disease recurrence in patients with venous thromboembolism. Data extraction: Patient level databases were obtained, transferred to a central database, checked, and completed with further information provided by authors. Data synthesis: 2554 patients with a first venous thromboembolism had follow-up for a mean of 27.1 (SD 19.6) months. The one year incidence of recurrent venous thromboembolism was 5.3% (95% confidence interval 4.1% to 6.7%) in women and 9.5% (7.9% to 11.4%) in men, and the three year incidence of recurrence was 9.1% (7.3% to 11.3%) in women and 19.7% (16.5% to 23.4%) in men. Among patients with unprovoked venous thromboembolism, men had a higher risk of recurrence than did women (hazard ratio 2.2, 95% confidence interval 1.7 to 2.8). After adjustment for women with hormone associated initial venous thromboembolism, the risk of recurrence remained higher in men (hazard ratio 1.8, 1.4 to 2.5). In patients with provoked venous thromboembolism, occurring after exposure to a major risk factor, recurrence of disease did not differ between men and women (hazard ratio 1.2, 0.6 to 2.4). In women with hormone associated venous thromboembolism and no other risk factors, recurrence was lower than that in women with unprovoked venous thromboembolism and no previous hormone use (hazard ratio 0.5, 0.3 to 0.8). Conclusion: In patients with a first unprovoked venous thromboembolism, men have a 2.2-fold higher risk of recurrent venous thromboembolism than do women, which remained 1.8-fold higher in men after adjustment for previous hormone associated venous thromboembolism in women. In patients with a first provoked venous thromboembolism, risk of recurrence does not differ between men and women with or without hormone associated venous thromboembolism. Indefinite anticoagulation may be given greater consideration in men than in women after a first venous thromboembolism
Report on the CoRoT Evolution and Seismic Tools Activity
No full textWe present the work undertaken by the Evolution and Seismic Tools Activity (ESTA) team of the CoRoT Seismology Working Group. We have focused on two main tasks: Task 1 now finished has aimed at testing, comparing and optimising seven stellar evolution codes which will be used to model the internal structure and evolution of the CoRoT target stars. Task 2, still underway, aims at testing, comparing and optimising different seismic codes used to calculate the oscillations of models for different types of stars. The results already obtained are quite satisfactory, showing minor differences between the different numerical tools provided the same assumptions on the physical parameters are made. This work gives us confidence on the numerical tools that will be available to interpret the future CoRoT seismic data
Does the clinical presentation and extent of venous thrombosis predict likelihood and type of recurrence? A patient-level meta-analysis
No full textAim: To determine if the mode of presentation of venous thromboembolism (VTE), as deep vein thrombosis (DVT) or pulmonary embolism (PE), predicts the likelihood and type of recurrence. Methods: We carried out a patient-level meta-analysis of seven prospective studies in patients with a first VTE who were followed after anticoagulation was stopped. We used Kaplan-Meier analysis to determine the cumulative incidence of recurrent VTE according to mode of presentation, and multivariable Cox regression to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for mode of and extent of DVT as potential risk factors for recurrence. Results: The 5-year cumulative rate of recurrent VTE in 2554 patients was 22.6%. In 869 (36.1%) patients with PE, the 5-year rate of any recurrence (DVT or PE) was 22.0%, and recurrence as PE was 10.6%. In 1365 patients with proximal DVT, the 5-year recurrence rate was 26.4%, and recurrence with PE was 3.6%. The risk of recurrence as PE was 3.1-fold greater in patients presenting with symptomatic PE than in patients with proximal DVT (HR, 3.1; 95% CI, 1.9-5.1). Patients with proximal DVT had a 4.8-fold higher cumulative recurrence rate than those with distal DVT (HR, 4.8; 95% CI, 2.1-11.0). Conclusion: Whilst DVT and PE are manifestations of the same disease, the phenotypic expression is predetermined. Patients presenting with PE are three times more likely to suffer recurrence as PE than patients presenting with DVT. Patients presenting with calf DVT are at low risk of recurrence and at low risk of recurrence as PE
Patient-level compared with study-level meta-analyses demonstrate consistency of D-dimer as predictor of venous thromboembolic recurrences
No full text<p>Objective: We compared the performance of aggregate data (AD)–based and individual patient data (IPD)–based meta-analyses to synthesize evidence on the ability of D-dimer to distinguish recurrence risk in patients with unprovoked venous thromboembolism (VTE) who stopped anticoagulation.</p>
<p>Study Design and Setting: We compared the results of the published AD-based rate ratio of VTE recurrence for positive vs. negative D-dimer, estimated by a mixed-effect Poisson model, with those of the IPD-based hazard ratio obtained by a Cox regression stratified by trial. We performed three additional analyses to investigate the methodological reasons for differences between the two approaches, comparing the IPD Cox regression with AD generated from IPD Poisson regression (to control for differences in population on study), AD time-to-event meta-analysis, and AD generated from IPD meta-regression.</p>
<p>Results: Published analyses agreed in direction and statistical significance when estimating the prognostic value of D-dimer even if IPD estimates suggested a stronger effect. The additional analyses suggested that differences in study populations might explain this slight difference. Poor reporting in published studies precluded a true comparison of AD- and IPD-based assessments of heterogeneity sources.</p>
<p>Conclusion: AD and IPD meta-analyses yielded similar estimates of D-dimer effect to distinguish risk for recurrent VTE. The IPD approach was justified by the need to investigate sources of heterogeneity.</p>
Report on the CoRoT Evolution and Seismic Tools Activity
No full textWe present the work undertaken by the Evolution and Seismic Tools Activity (ESTA) team of the CoRoT Seismology Working Group. We have focused on two main tasks: Task 1 now finished has aimed at testing, comparing and optimising seven stellar evolution codes which will be used to model the internal structure and evolution of the CoRoT target stars. Task 2, still underway, aims at testing, comparing and optimising different seismic codes used to calculate the oscillations of models for different types of stars. The results already obtained are quite satisfactory, showing minor differences between the different numerical tools provided the same assumptions on the physical parameters are made. This work gives us confidence on the numerical tools that will be available to interpret the future CoRoT seismic data
and elastic scattering at 6.2 GeV/c
No full textData on 6.2 GeV/c pi /sup -/p and K/sup -/p elastic scattering cross sections are presented in the range 0.3<-t<10.7 (GeV/c)/sup 2/. Large- angle pi /sup -/p scattering differential cross sections oscillate around an average differential cross section of 50 nb/(GeV/c)/sup 2/, with minima at cos theta /sub cm/ approximately=0 and -0.4. The well- known dip at -t=2.8 (GeV/c)/sup 2/ remains constant in t. In the backward direction there is a dip at -u approximately=1 (GeV/c)/sup 2 /. K/sup -/p elastic scattering has a diffraction peak with a slope of 7.30+or-0.08 (GeV/c)/sup -2/ in the region 0.3<-t<0.6 (GeV/c)/sup 2/. The structure at about -t=1 (GeV/c)/sup 2/ is less pronounced than at 5 GeV/c. The large-angle region is characterized by a very fast decrease of the differential cross section with increasing energy. (67 refs)
Risk of recurrence after venous thromboembolism in men and women: patient level meta-analysis.
No full textannihilation into at 5 GeV/c
No full textThe authors have measured the differential cross-section for the reaction pp to pi /sup +/ rho /sup -/ at 5 GeV/c, the pi /sup +/ being in the cm angular range 0.47<cos theta /sub p pi +//sup cm/<0.98, corresponding to 0.12<-t<2.40 (GeV/c)/sup 2/. The angular distribution has a forward peak with a differential cross-section d sigma /d Omega =4.1+or-1.6 mu b/sr for 0.94<cos theta /sub p pi +//sup cm/<0.96. (8 refs)
Risk of recurrence after a first unprovoked venous thromboembolism : external validation of the Vienna Prediction Model with pooled individual patient data
No full textBackground: In order to stratify patients with a first unprovoked venous thromboembolism (VTE) according to their recurrence risk and to identify those who would actually benefit from indefinite anticoagulation, three prediction models have been developed so far; none of them has been yet externally validated. Objective: To externally validate the Vienna Prediction Model (VPM), a prediction guide for estimating the recurrence risk after a first unprovoked VTE developed through Cox modeling and including sex, D-dimer and index VTE site as predictors. Patients/Methods: Nine hundred and four patients pooled from five prospective studies evaluating the prognostic value of D-dimer for VTE recurrence served as the validation cohort. The validity of the VPM in stratifying patients according to their relative recurrence risk (discrimination) and in predicting the absolute recurrence risk (calibration) was tested with survival analysis methods. Results: The ability of the VPM to distinguish patients' risk for recurrent VTE in the validation cohort was at least as good as in the original cohort, with a calibration slope of 1.17 (95% confidence interval 0.71-1.64; P = 0.456 for the hypothesis of a significant difference from 1), and a c-statistic of 0.626 (vs. 0.651 in the original derivation cohort). The VPM absolute predictions in terms of cumulative rates tended to underestimate the observed recurrence rates at 12 months. Conclusions: By using a pooled individual patient database as a validation cohort, we confirmed the ability of the VPM to stratify patients with a first unprovoked VTE according to their risk of recurrence
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