167 research outputs found

    Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

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    Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

    RESEARCH ON DAMAGE ZONE IN STRESS FIELD INTENSITY METHOD

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    In view of the controversial problem of damage zone in stress field intensity method,a method was proposed to determine damage zone by stress contour. Stress contour calculating steps were given. The example was given to demonstrate the calculating process. The result of the example analysis shows that the damage zone is not a regular and spherical zone,but is irregular. The method can reflect the real damage zone and is accord with the fatigue mechanism. The damage zone size and the load applied show a quadratic curve relationship and monotone increase. This method considers the changing load’s effect on the damage zone and even large load is applied it still can accurately predict the fatigue life of components. In order to prove the universality of the method,two examples with different notch shapes and load forms were given to verify. The result shows that the method can accurately predict the fatigue life of components with any notch shape and any load form and good predicted results have been achieved

    Complex between bovine ribonuclease A and porcine ribonuclease inhibitor crystallizes in a similar unit cell as free ribonuclease inhibitor

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    We obtained three different morphologies of crystals of bovine ribonuclease A and porcine ribonuclease inhibitor. X-ray quality crystals were grown in 1·3 M ammonium sulfate, 100 mM sodium acetate (pH 5·0) and 20 mM dithiothreitol at 21°C. These crystals have the symmetry of the tetragonal space group I4 with a=133·3 Å and c =86·7 Å and diffract to 2·5 Å resolution; they have the same symmetry and only slightly different cell parameters than the crystals of free ribonuclease inhibitor. Polyacrylamide gel electrophoresis and the crystal density indicate that both ribonuclease inhibitor and ribonuclease A are present in the crystals. Although small, crystals are suitable for three-dimensional structural analysis
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