Preliminary psychometric properties of the Acceptance and Action Questionnaire – II: A revised measure of psychological flexibility and acceptance.

The present research describes the development and psychometric evaluation of a second version of the Acceptance and Action Questionnaire (AAQ-II), which assesses the construct referred to as, variously, acceptance, experiential avoidance and psychological inflexibility. Results from 2,816 participants across six samples indicate the satisfactory structure, reliability, and validity of this measure. For example, the mean alpha coefficient is .84 (.78 - .88), and the 3- and 12-month test-retest reliability is .81 and .79, respectively. Results indicate that AAQ-II scores concurrently, longitudinally, and incrementally predict a range of outcomes, from mental health to work absence rates,that are consistent with its underlying theory. The AAQ-II also demonstrates appropriate discriminant validity. The AAQ-II appears to measure the same concept as the AAQ-I (r = .97), but with better psychometric consistency

Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Evaluation of a bovine colostral preparation as treatment for gastrointestinal injury

Growth factors play an important role in repair of the injured gut as well as maintaining gut homeostasis. De-fatted bovine colostrum is a health food supplement containing significant amounts of growth factors. Thus, derivatives from bovine colostrum might be an inexpensive treatment for gut injury (e.g. inflammatory bowel disease (IBD)), and as a prophylactic against injurious effects of drugs such as non-steroidal anti-inflammatory drugs (NSAIDs).;The studies presented in this thesis were devised to test the effects of a commercially-available bovine colostral preparation on wound healing and proliferation in vitro, and in an animal model of IBD. The effect of TGF2, a major colostral growth factor, on NSAID-induced murine small intestinal injury was also tested. Finally, the effects of bovine colostral preparation on intracellular signalling leading to stimulated DNA synthesis was investigated.;Bovine colostral preparation stimulated DNA synthesis and proliferation in cultured intestinal epithelial cells, and also stimulated epithelial migration following wounding. Motogenic effects were independent of proliferation. Colostral components greater than 30 kDa in weight were mostly responsible for these effects.;Motogenic, but not mitogenic, components were resistant to transient acidification, such as might be encountered in the stomach. Transient acidification liberated active TGF. TGF2, the major colostral TGF isoform, was prophylactic against murine small intestinal NSAID-induced damage.;Oral bovine colostral preparations stimulated healing of chemically-induced colitis in rats, but had no effect on the induction of colitis. Topical application of the colostral preparation by enema was ineffective.;Inhibition of growth factor receptors inhibited some, but not all, proliferative activity in colostral preparation. Some effects of colostral preparation were due to activation of the EGF receptor despite the absence of EGF in the preparation.;In conclusion, bovine colostral preparation might act as an orally-active prophylactic and healing agent for a variety of gastrointestinal injuries

Technological Forecasting---Model Selection, Model Stability, and Combining Models

The paper identifies 29 models that the literature suggests are appropriate for technological forecasting. These models are divided into three classes according to the timing of the point of inflexion in the innovation or substitution process. Faced with a given data set and such a choice, the issue of model selection needs to be addressed. Evidence used to aid model selection is drawn from measures of model fit and model stability. An analysis of the forecasting performance of these models using simulated data sets shows that it is easier to identify a class of possible models rather than the 'best' model. This leads to the combining of model forecasts. The performance of the combined forecasts appears promising with a tendency to outperform the individual component models.Innovation Diffusion, Model Selection, Combination of Forecasts, Logistic Curve