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

Etruscan Tomb Paintings, their subjects and significance. By F. Poulsen. Translated by I. Andersen, X + 63 pp., 47 illustrations. Clarendon Press, 1922.

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Italian fictile antefixes of the Πότνια θηρῶν

Douglas Van Buren E. Italian fictile antefixes of the Πότνια θηρῶν. In: Revue des Études Anciennes. Tome 24, 1922, n°2. pp. 93-100

Standard Operating Procedures for Biospecimen Collection, Processing, and Storage

High-quality and well-annotated biorepositories are needed to better understand the pathophysiology and biologic mechanisms of chronic pancreatitis (CP) and its consequences. We report a methodology for the development of a robust standard operating procedure (SOP) for a biorepository based on the experience of the clinical centers within the consortium to study Chronic Pancreatitis, Diabetes and Pancreas Cancer Clinical Centers (CPDPC), supported by the National Cancer Institute and the National Institute for Diabetes and Digestive and Kidney Diseases as a unique multidisciplinary model to study CP, diabetes, and pancreatic cancer in both children and adults. Standard operating procedures from the CPDPC centers were evaluated and consolidated. The literature was reviewed for standard biorepository operating procedures that facilitated downstream molecular analysis. The existing literature on biobanking practices was harmonized with the SOPs from the clinical centers to produce a biorepository for pancreatic research. This article reports the methods and basic principles behind the creation of SOPs to develop a biorepository for the CPDPC. These will serve as a guide for investigators developing biorepositories in pancreas research. Rigorous and meticulous adherence to standardized biospecimen collection will facilitate investigations to better understand the pathophysiology and biologic mechanisms of CP, diabetes, and pancreatic cancer

Hoover Dam and the Evolution of Uplift Theory

The earliest technical article by an American engineer on hydraulic uplift was the ASCE Presidential Address by James B. Francis in 1888. He suggested applying full hydrostatic pressure at the upstream heel of a dam, diminishing to zero pressure at the downstream toe. Thoughts on the potentially destabilizing role of uplift were mentioned by John R. Freeman in 1911 in his comments on the failure of Bayless Dam near Austin, PA. Between 1911-1918 Arnold C. Koenig, J. B. T. Coleman, and James B. Hays discussed how to account for uplift in masonry dams in the ASCE Proceedings and Transactions. Up until 1927-28 most engineers assumed that uplift pressure was tied to the permeability of the foundation and that of the dam structure. Most assumed that concrete was impervious and incapable of transmitting meaningful pore pressure. The textbooks cited by the engineers who drafted the plans for the St. Francis Dam cited examples that appeared in textbooks published between 1908-18. In 1918 Edward Wegmann asserted that it was impossible to accurately estimate the uplift that might develop beneath a dam and that engineers should rely on their own judgment. Others suggested that an uplift pressure diagram in the shape of a trapezoid be employed, assuming development of two-Thirds the theoretical uplift, varying lineally to zero at the toe, unless uplift relief wells were employed. All the various theories were called into question when Hoover Dam was filled to capacity in 1934-41 and excessive uplift pressures developed beneath the dam\u27s downstream face. This led to tripling the depth of the grout curtain, which took nine years complete. In 1936 Karl Terzaghi introduced his theory of effective stress, which established a distinction between total stress and those ascribable to hydrostatic (pore water) pressure. In 1939 ASCE formed a Subcommittee on Uplift in Masonry Dams. In 1945 Terzaghi summarized the results of experimental work that suggested water was able to transmit pore pressures in concrete. The ASCE committee released their final report in 1952, which included uplift measurements of a modest number of high-head dams and commented on what they felt constituted reasonable bounds on how much uplift could develop if relief wells were installed immediately downstream of grout curtains

A Critical Perspective of Integrative Social Contracts Theory: Recurring Criticisms and Next Generation Research Topics

During the past ten years Integrative Social Contracts Theory (ISCT) has become part of the repertoire of specialized decision-oriented theories in the business ethics literature. The intention here is to (1)â\x90£provide a brief overview of the structure and strengths of ISCT; (2) identify recurring themes in the extensive commentary on the theory including brief mention of how ISCT has been applied outside the business ethics literature; (3) describe where research appears to be headed; and (4) specify challenges faced by those who seek to reform ISCT. Key themes in the critiquing literature relate to (a) the identification process for hypernorms; (b) justification of the recognition of hypernorms; (c) proposals for considering meso or meta norms; (d)â\x90£clarification of the relationship between stakeholder concepts and ISCT; (e) problems with potentially unoccupied moral free space; (f) sources of ethical obligation within the ISCT framework; and (g) the potential role for concepts of stakeholder dialogue and engagement. Copyright Springer Science+Business Media, Inc. 2006social contract, integrative social contracts theory, moral free space, hypernorms, stakeholder theory,