New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Visualising a “good game”:analytics as a calculative engine in a digital environment

Abstract Purpose: The purpose of this paper is to concern the use of analytics as a calculative engine enabling coordination and control for the development process in a creative digital business environment. Design/methodology/approach: This research employs an explorative field study approach, using interview data from professionals working with free-to-play mobile game development. Drawing on the concepts of cycles of accumulation, accounting as an engine and mediating instruments, this study examines how organisational actors using the analytics in a digital business environment participate in the data generation that accumulates knowledge about and new insights into the desired outcome. Findings: The real-time metrics provided the means for organisational actors to continually monitor, visualise and if necessary intervene in the creative “good game” development process. Timely quantification and visualisation of user actions, collected as digital traces, enhanced the cycle of information accumulation. This new knowledge resulted in a desire for improvement and perfection, which directed the actions towards the organisational objectives. Originality/value: This study furthers our understanding of the performativity of accounting as an engine and the user behavioural data trace as its “fuel” in a digital product development. It highlights the role of analytics as a “fact-generating” device, capable of transforming the raw user behavioural data, the fuel, into powerful explanations through visualisations of ideals. The real-time metrics, understood as mediating instruments, enable the generation of new insights and accumulation of knowledge guiding the further development towards the desired outcome, the “good game”

The standard point-of-care Hemochron Jr. ACT+ test in monitoring heparin administration for cardiopulmonary bypass in severe factor XII deficiency

Abstract Coagulation factor XII (FXII) is a plasma serine protease that belongs to the contact activation complex responsible for initiating the intrinsic coagulation pathway. FXII deficiency is a rare congenital disorder that is not associated with an increased tendency for bleeding. However, as contact activation is impaired in FXII deficiency, both the celite- and kaolin-initiated activated clotting time (ACT) measurements are prolonged markedly, which poses a challenge for anticoagulation monitoring in patients undergoing cardiac surgery. The authors successfully have used the standard Hemochron Jr. ACT+ test, which is activated by silica and phospholipid in addition to kaolin, to monitor anticoagulation for cardiopulmonary bypass in two patients with severe FXII deficiency. The ACT+ test showed low baseline values, increased adequately in response to heparin, and decreased to baseline after protamine. Importantly, there was no abnormal intra- or postoperative bleeding nor any thrombotic complications. Furthermore, in vitro dose-response ACT+ testing of FXII-deficient blood with increasing heparin concentrations supports the use of ACT+ in FXII deficiency

Coronary Artery Disease–Associated Locus on Chromosome 9p21 and Early Markers of Atherosclerosis

Background— Genome-wide association studies have recently identified a locus on chromosome 9p21 that influences risk of coronary artery disease (CAD). The effect of the locus on early markers of atherosclerosis is unknown. We examined its association with carotid intima-media thickness (CIMT) and brachial flow-mediated dilatation (FMD). Methods and Results— We genotyped 2277 individuals, age 24 to 39 years, from the Cardiovascular Risk in Young Finns Study with CIMT and FMD measurements and 1295 individuals, age 46 to 76 years, from the Health 2000 Survey with CIMT for rs1333049, the chromosome 9p21 variant showing the strongest association with CAD. Both mean and maximum CIMT were significantly higher (P<0.001) in the older subjects of the Health 2000 Survey compared with the Young Finns Study. However, there was no association of the rs1333049 genotype with either mean or maximum CIMT at either age (P=0.959 and 0.977 for the 2 phenotypes in the Young Finns Study and P=0.714 and 0.725 in the Health 2000 Survey). Similarly, there was no association of the locus with variation in FMD in the Young Finns cohort (P=0.521). Conclusions— The chromosome 9p21 locus does not influence CAD risk through a mechanism that also affects CIMT or induces early changes in FMD. We examined the association with carotid intima-media thickness and brachial flow mediated dilatation of the recently identified susceptibility locus for coronary artery disease on chromosome 9p21. We found no evidence that the risk variant affects either of these early markers of atherosclerosis, suggesting an alternate mechanism for its effect on risk of CAD