Genomic insights into the causes of type 2 diabetes.

Genome-wide association studies have implicated around 250 genomic regions in predisposition to type 2 diabetes, with evidence for causal variants and genes emerging for several of these regions. Understanding of the underlying mechanisms, including the interplay between β-cell failure, insulin sensitivity, appetite regulation, and adipose storage has been facilitated by the integration of multidimensional data for diabetes-related intermediate phenotypes, detailed genomic annotations, functional experiments, and now multiomic molecular features. Studies in diverse ethnic groups and examples from population isolates have shown the value and need for a broad genomic approach to this global disease. Transethnic discovery efforts and large-scale biobanks in diverse populations and ancestries could help to address some of the Eurocentric bias. Despite rapid progress in the discovery of the highly polygenic architecture of type 2 diabetes, dominated by common alleles with small, cumulative effects on disease risk, these insights have been of little clinical use in terms of disease prediction or prevention, and have made only small contributions to subtype classification or stratified approaches to treatment. Successful development of academia-industry partnerships for exome or genome sequencing in large biobanks could help to deliver economies of scale, with implications for the future of genomics-focused research

Prioritising Risk Factors for Type 2 Diabetes: Causal Inference through Genetic Approaches.

PURPOSE OF THE REVIEW: Causality has been demonstrated for few of the many putative risk factors for type 2 diabetes (T2D) emerging from observational epidemiology. Genetic approaches are increasingly being used to infer causality, and in this review, we discuss how genetic discoveries have shaped our understanding of the causal role of factors associated with T2D. RECENT FINDINGS: Genetic discoveries have led to the identification of novel potential aetiological factors of T2D, including the protective role of peripheral fat storage capacity and specific metabolic pathways, such as the branched-chain amino acid breakdown. Consideration of specific genetic mechanisms contributing to overall lipid levels has suggested that distinct physiological processes influencing lipid levels may influence diabetes risk differentially. Genetic approaches have also been used to investigate the role of T2D and related metabolic traits as causal risk factors for other disease outcomes, such as cancer, but comprehensive studies are lacking. Genome-wide association studies of T2D and metabolic traits coupled with high-throughput molecular phenotyping and in-depth characterisation and follow-up of individual loci have provided better understanding of aetiological factors contributing to T2D

Supergravity origin of the MSSM inflation

We consider the supergravity origin of the recently proposed MSSM inflationary model, which relies on the existence of a saddle point along a dimension six flat direction. We derive the conditions that the Kahler potential has to satisfy for the saddle point to exist irrespective of the hidden sector vevs. We show that these conditions are satisfied by a simple class of Kahler potentials, which we find to have a similar form as in various string theory compactifications. For these potentials, slow roll MSSM inflation requires no fine tuning of the soft supersymmetry breaking parameters.Comment: v3: 10 pages, no figures; version accepted for publication. Typos correcte

Adenosine triphosphatases of thermophilic archaeal double-stranded DNA viruses

Peer reviewe

Novel Ex Vivo DOAC Removal Methods Reduce Interference in Lupus Anticoagulant Testing

Direct oral anticoagulants (DOAC) interfere in laboratory coagulation testing. The aim here was to study how commercial DOAC removal methods, DOAC Filter® and DOAC-Stop™, perform to eliminate DOAC concentrations and false positive results in lupus anticoagulant (LAC) testing. We acquired 50 patient samples with high concentrations of DOACs: apixaban (n = 18, range 68–572 ng/mL), dabigatran (n = 8, range 47–154 ng/mL), edoxaban (n = 8, range 35–580 ng/mL) and rivaroxaban (n = 16, range 69–285 ng/mL). DOACs were removed ex vivo with either DOAC Filter® (n = 28) or DOAC-Stop™ (n = 22). Additionally, commercial control and calibrator samples were studied (n = 13 for DOAC Filter®, n = 14 for DOAC-Stop™). LAC screening was performed before and after DOAC removal. Both DOAC Filter® and DOAC-Stop™ were effective in removing DOAC concentrations in samples: DOAC concentrations decreased to median of 0 ng/mL (range 0–48 ng/mL). Only one sample had more than residual 25 ng/mL of DOAC (apixaban). Before DOAC removal, 96% (48/50) of patient samples and over 90% (12/13 DOAC Filter®, 13/14 DOAC-Stop™) of control/calibrator samples were positive in the LAC screening. In patient samples, LAC screening turned negative in 61% (17/28) after DOAC Filter® and 45% (10/22) after DOAC-Stop™ treatment. All control samples became negative after DOAC removal. In conclusion, DOAC removal ex vivo reduces false positives in LAC screening. DOAC removal halved the need for confirmation or mixing tests- Although a subset of patients would require further testing, DOAC removal reduces unnecessary repeated LAC testing

Blurring the Boundaries: Reflecting on PDS Roles and Responsibilities through Multiple Lenses

It is well documented that successful Professional Development School (PDS) initiatives are contingent on trusting relationships between the university and school districts

Infant feeding practices in Bhaktapur, Nepal: a cross-sectional, health facility based survey

<p>Abstract</p> <p>Background</p> <p>Promotion of proper breastfeeding practices for the first six months of life is the most cost-effective intervention for reducing childhood morbidity and mortality. However, the adherence to breastfeeding recommendations in many developing countries is not satisfactory. The aims of the study were to determine breastfeeding and infant feeding patterns at nine months of age and to assess factors influencing exclusive breastfeeding practices.</p> <p>Methods</p> <p>In Bhaktapur, Nepal, we carried out a cross-sectional survey of 325 infants who came for measles vaccination at the age of nine months. Mothers were interviewed on details regarding feeding of their child and health since birth.</p> <p>Results</p> <p>Three quarters of all mothers reported that they did not receive any information on breastfeeding during the antenatal visit. Two hundred and ninety five (91%) mothers gave colostrum and 185 (57%) initiated breastfeeding within one hour of delivery. The prevalence of exclusively breastfeeding at 1, 3 and 6 months were 240 (74%), 78 (24%) and 29 (9%), and partial feeding was initiated in 49 (15%), 124 (38%) and 257 (79%) babies, respectively. The main reason, according to the mother, for introducing other foods before six months of age was insufficient breast milk. In logistic regression analyses, mother's knowledge on how long child should be given only breast milk and not living in joint families were associated positively with exclusive or predominant breastfeeding for four months or beyond.</p> <p>Conclusions</p> <p>Despite the high proportion of mothers who initiated breastfeeding immediately after birth, continuation of exclusive breastfeeding for up to six months was not common. Very few mothers received any information on breastfeeding during the antenatal visit, indicating a need for counseling on exclusive breastfeeding. Possible options for this counseling could be during antenatal visits and at regular clinic visits for vaccination.</p