Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140?mm?Hg systolic blood pressure or ≥90?mm?Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.     

Application of Viable System Model in Diagnosis of Organizational Structure

Systemic Practice and Action Research - A well-designed organizational structure is a cornerstone of achieving an organization’s goals while suiting the environmental challenges. Structural...     

Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10(-8)). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events.     

Stochastic framework for reliability enhancement using optimal feeder reconfiguration

Optimal distribution feeder reconfiguration （DFR） is a valuable and costless approach to increase the load balance, reduce the amount of power losses, and improve the voltage of the buses. In this way, this paper aims to investigate the optimal DFR strategy as a proper tool to improve the reliability of the radial distribution networks. The idea of failure rate reduction is employed to see the effect of feeder current reduction on the reliability of the system more accurately. The objects to be investigated are system average interruption frequency index （SAIFI）, system average interruption duration index （SAIDI）, average energy not supplied （AENS） and total active power losses. The problem is then formulated in a stochastic framework based on the point estimate method （PEM） to handle the uncertainty effects. The feasibility and satisfying performance of the proposed method is examined on a standard IEEE test system.     

The Critical Heuristics of Iranian Banking Credit System: Analysis of the Antithetical Opinions of the Beneficiaries

Systemic Practice and Action Research - Considering the unfortunate intensification of the Non-performing loans in Iran`s credits system makes it vital to study the current system shortcomings....