Social Security: a conceptual view

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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

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

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P = 9.2 x 10(-20)), ER-negative BC (P = 1.1 x 10(-13)), BRCA1-associated BC (P = 7.7 x 10(-16)) and triple negative BC (P-diff = 2 x 10(-5)). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P = 2 x 10(-3)) and ABHD8 (PPeer reviewe

Winsdeelskemas : 'n alternatiewe oplossing vir onrealistiese looneise

M.Com. (Business Management)A higher standard of living is one of the greatest needs of the South African population. Labour movements believe that a higher standard of living can actually be achieved by paying higher wages. Unfortunately higher wages are demanded and paid at the expense of productivity which is a vital ingredient for economic growth and ultimately economic survival. Employers within the South African economy can address the low productivity ratios through the implementation of performance related schemes. Gain sharing is one of many interventions management can implement to achieve greater performance through labour. By implementing a gain sharing scheme management is able to relate pay to performance and address efficiency ratios which ultimately affects the competitiveness of South African goods and services against world competitors

Why cordylid lizards are black at the south-western tip of Africa

The original publication is available at http://onlinelibrary.wiley.com/There is a high incidence of melanism among the cordylid lizards of Africa and it was suggested that melanism has a thermoregulatory function in these species. One prediction of the thermal melanism hypothesis would be that melanistic cordylid species would be restricted to cool environments. The aim of our study was to determine the climatic conditions with which melanistic cordylids are currently associated.Distributional data for the eight melanistic cordylid taxa occurring at the south-western tip of Africa were obtained from the CapeNature State of Biodiversity database. Using GIS and principal component analyses, the climatic variables best describing the geographical distribution of melanistic cordylids were investigated. We found that several melanistic cordylid populations show a distinct association with a high incidence of fog and cloud cover, underscoring the thermal melanism hypothesis. Several other populations, however, do not show such an association. We conclude that some species, such as Pseudocordylus capensis, have a morphology that provides them with great flexibility in habitat use, allowing them to overcome the constraints of melanism in warm environments. The available information suggests that melanism in cordylids evolved during the Miocene in response to the development of the cold Benguela Current along the west coast of Africa.We also conclude that viviparity, a sit-and-wait foraging strategy and a rockdwelling lifestyle would have preadapted cordylids for survival in cool conditions brought about by the development of the cold Benguela Current. These conditions would have been unfavourable for oviparous, active-foraging lizards. The cooccurrence ofmelanistic lizards andmelanistic molluscs at the Landdroskop locality casts some doubt on improved heating rates as the only explanation for melanism in cordylids, because molluscs are not heliothermic baskers.Publishers' Versio