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

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

On focusing of strong shock waves

Focusing of strong shock waves in a gas-filled thin test section with various forms of the reflector boundary is investigated. The test section is mounted at the end of the horizontal co-axial shock tube. Two different methods to produce shock waves of various forms are implemented. In the first method the reflector boundary of the test section is exchangeable and four different reflectors are used: a circle, a smooth pentagon, a heptagon and an octagon. It is shown that the form of the converging shock wave is influenced both by the shape of the reflector boundary and by the nonlinear dynamic interaction between the shape of the shock and the propagation velocity of the shock front. Further, the reflected outgoing shock wave is affected by the shape of the reflector through the flow ahead of the shock front. In the second method cylindrical obstacles are placed in the test section at various positions and in various patterns, to create disturbances in the flow that will shape the shock wave. It is shown that it is possible to shape the shock wave in a desired way by means of obstacles. The influence of the supports of the inner body of the co-axial shock tube on the form of the shock is also investigated. A square shaped shock wave is observed close to the center of convergence for the circular and octagonal reflector boundaries but not in any other setups. This square-like shape is believed to be caused by the supports for the inner body. The production of light, as a result of shock convergence, has been preliminary investigated. Flashes of light have been observed during the focusing and reflection process.QC 2010112

On focusing of shock waves

Both experimental and numerical investigations of converging shock waves have been performed. In the experiments, a shock tube was used to create and study converging shock waves of various geometrical shapes. Two methods were used to create polygonally shaped shocks. In the first method, the geometry of the outer boundary of the test section of the shock tube was varied. Four different exchangeable shapes of the outer boundary were considered: a circle, a smooth pentagon, a heptagon, and an octagon. In the second method, an initially cylindrical shock wave was perturbed by metal cylinders placed in various patterns and positions inside the test section. For three or more regularly spaced cylinders, the resulting diffracted shock fronts formed polygonal shaped patterns near the point of focus. Regular reflection was observed for the case with three cylinders and Mach refection was observed for cases with four or more cylinders. When the shock wave is close to the center of convergence, light emission is observed. An experimental investigation of the light emission was conducted and results show that the shape of the shock wave close to the center of convergence has a large influence on the amount of emitted light. It was found that a symmetrical polygonal shock front produced more light than an asymmetrical shape. The shock wave focusing was also studied numerically using the Euler equations for a gas obeying the ideal gas law with constant specific heats. Two problems were analyzed; an axisymmetric model of the shock tube used in the experiments and a cylindrical shock wave diffracted by cylinders in a two dimensional test section. The results showed good agreement with the experiments. The temperature field from the numerical simulations was investigated and shows that the triple points behind the shock front are hot spots that increase the temperature at the center as they arrive there. As a practical example of shock wave focusing, converging shocks in an electrohydraulic lithotripter were simulated. The maximum radius of a gas bubble subjected to the pressure field obtained from the lithotripter was calculated and compared for various geometrical shapes and materials of the reflector. Results showed that the shape had a large impact while the material did not influence the maximum radius of the gas bubble.QC 2010070

Numerical Study of Shock Wave Attenuation in Two-Dimensional Ducts Using Solid Obstacles: How to Utilize Shock Focusing Techniques to Attenuate Shock Waves

Research on shock wave mitigation in channels has been a topic of much attention in the shock wave community. One approach to attenuate an incident shock wave is to use obstacles of various geometries arranged in different patterns. This work is inspired by the study from Chaudhuri et al. (2013), in which cylinders, squares and triangles placed in staggered and non-staggered subsequent columns were used to attenuate a planar incident shock wave. Here, we present numerical simulations using a different obstacle pattern. Instead of using a matrix of obstacles, an arrangement of square or cylindrical obstacles placed along a logarithmic spiral curve is investigated, which is motivated by our previous work on shock focusing using logarithmic spirals. Results show that obstacles placed along a logarithmic spiral can delay both the transmitted and the reflected shock wave. For different incident shock Mach numbers, away from the logarithmic spiral design Mach number, this shape is effective to either delay the transmitted or the reflected shock wave. Results also confirm that the degree of attenuation depends on the obstacle shape, effective flow area and obstacle arrangement, much like other obstacle configurations

Creep in amorphous metals

This paper reviews the work on creep behavior of amorphous metals. There have been, over the past several years, a few reviews of the mechanical behavior of amorphous metals. Of these, the review of the creep properties of amorphous metals by Schuh et al. though oldest of the three, is particularly noteworthy and the reader is referred to this article published in 2007. The current review of creep of amorphous metals particularly focuses on those works since that review and places the work prior to 2007 in a different context where new developments warrant

In-situ Optical Investigations of Hypervelocity Impact Induced Dynamic Fracture

Two independent optical methods are used to analyze the dynamic material behavior of Mylar and Homalite-100 subjected to hypervelocity impact. Birefringent targets are loaded in tension inside a two-stage light-gas gun vacuum chamber, and are impacted with a 5 mg nylon slug at velocities between 3 and 6 km/s. Caustics and photoelasticity combined with high-speed photography are used to determine dynamic stress intensity behavior around the crack tip during and after impact. Homalite-100 lower crack tip speeds are subjected to reflecting boundary shear waves from the nylon impact, and thereby the crack path exhibits distinct kinks; whereas Mylar higher crack tip speeds provides distinguishable isochromatic patterns and an unadulterated fracture surface. Shear wave patterns in the target from photoelastic effects are compared to results from numerical simulations using the Overture Suite, which solves linear elasticity equations on overlapping curvilinear grids by means of adaptive mesh refinement

Numerical and experimental investigation of oblique shock wave reflection off a water wedge

Shock wave interaction with solid wedges has been an area of much research in past decades, but so far, very few results have been obtained for shock wave reflection off liquid wedges. In this study, numerical simulations are performed using the inviscid Euler equations and the stiffened gas equation of state to study the transition angles, reflection patterns, and triple point trajectory angles of shock reflection off solid and water wedges. Experiments using an inclined shock tube are also performed and schlieren photography results are compared to simulations. Results show that the transition angles for the water wedge cases are within 5.3% and 9.2%, for simulations and experiments respectively, compared to results obtained with the theoretical detachment criterion for solid surfaces. Triple point trajectory angles are measured and compared with analytic solutions, agreement within 1.3◦ is shown for the water wedge cases. The transmitted wave in the water observed in the simulation is quantitatively studied, and two different scenarios are found. For low incident shock Mach numbers, Ms = 1.2 and 2, no shock wave is formed in the water but a precursor wave is induced ahead of the incident shock wave and passes the information from the water back into the air. For high incident shock Mach numbers, Ms = 3 and 4, precursor waves no longer appear but instead a shock wave is formed in the water and attached to the Mach stem at every instant. The temperature field in the water is measured in the simulation. For strong incident shock waves, e.g., Ms = 4, the temperature increment in the water is up to 7.3K