The global and regional impacts of climate change under Representative Concentration Pathway forcings and Shared Socioeconomic Pathway socioeconomic scenarios

This paper presents an evaluation of the global and regional consequences of climate change for heat extremes, water resources, river and coastal flooding, droughts, agriculture and energy use. It presents change in hazard and resource base under different rates of climate change (Representative Concentration Pathways: RCP), and socio-economic impacts are estimated for each combination of RCP and Shared Socioeconomic Pathway. Uncertainty in the regional pattern of climate change is characterised by CMIP5 climate model projections. The analysis adopts a novel approach using relationships between level of warming and impact to rapidly estimate impacts under any climate forcing. The projections provided here can be used to inform assessments of the implications of climate change. At the global scale all the consequences of climate change considered here are adverse, with large increases under the highest rates of warming. Under the highest forcing the global average annual chance of a major heatwave increases from 5% now to 97% in 2100, the average proportion of time in drought increases from 7% to 27%, and the average chance of the current 50-year flood increases from 2% to 7%. The socio-economic impacts of these climate changes are determined by socio-economic scenario. There is variability in impact across regions, reflecting variability in projected changes in precipitation and temperature. The range in the estimated impacts can be large, due to uncertainty in future emissions and future socio-economic conditions and scientific uncertainty in how climate changes in response to future emissions. For the temperature-based indicators, the largest source of scientific uncertainty is in the estimated magnitude of equilibrium climate sensitivity, but for the indicators determined by precipitation the largest source is in the estimated spatial and seasonal pattern of changes in precipitation. By 2100 the range across socio-economic scenario is often greater than the range across the forcing levels

Primary coronary artery bypass surgery in the presence of decreasing preoperative renal function: effect on short-term outcomes

Background: This study evaluated the impact of decreasing renal function on short-term outcomes in patients undergoing primary coronary artery bypass grafting (CABG). Methods: The study period was from February 1999 to February 2009. Data on 4050 patients undergoing primary CABG were prospectively collected and analyzed retrospectively. The study population was divided into 3 groups: the CABG:N group, patients with preoperative serum creatinine levels 2 mg/dL (n = 87); and the CABG:D group, patients on dialysis (n = 16). Results: The significant differences between the groups (CABG:D > CABG:RF > CABG:N) in short-term outcomes were with respect to blood product use (P < .001), postoperative acute myocardial infarction (P < .001), pulmonary complications (P .001), infection (P < .001), and death (P < .001). The risk of short-term death (30 days) in the CABG:D group (4/16, 25%) was 25 times greater than that in the CABG:N group (38/3947, 0.96%). Conclusion: CABG in the presence of renal failure is associated with significant morbidity and mortality

Selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription

AbstractBackground: Glycogen synthase kinase-3 (GSK-3) is a serine/threonine protein kinase, the activity of which is inhibited by a variety of extracellular stimuli including insulin, growth factors, cell specification factors and cell adhesion. Consequently, inhibition of GSK-3 activity has been proposed to play a role in the regulation of numerous signalling pathways that elicit pleiotropic cellular responses. This report describes the identification and characterisation of potent and selective small molecule inhibitors of GSK-3.Results: SB-216763 and SB-415286 are structurally distinct maleimides that inhibit GSK-3α in vitro, with Kis of 9 nM and 31 nM respectively, in an ATP competitive manner. These compounds inhibited GSK-3β with similar potency. However, neither compound significantly inhibited any member of a panel of 24 other protein kinases. Furthermore, treatment of cells with either compound stimulated responses characteristic of extracellular stimuli that are known to inhibit GSK-3 activity. Thus, SB-216763 and SB-415286 stimulated glycogen synthesis in human liver cells and induced expression of a β-catenin-LEF/TCF regulated reporter gene in HEK293 cells. In both cases, compound treatment was demonstrated to inhibit cellular GSK-3 activity as assessed by activation of glycogen synthase, which is a direct target of this kinase.Conclusions: SB-216763 and SB-415286 are novel, potent and selective cell permeable inhibitors of GSK-3. Therefore, these compounds represent valuable pharmacological tools with which the role of GSK-3 in cellular signalling can be further elucidated. Furthermore, development of similar compounds may be of use therapeutically in disease states associated with elevated GSK-3 activity such as non-insulin dependent diabetes mellitus and neurodegenerative disease

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

Prediction of preeclampsia risk in first time pregnant women: Metabolite biomarkers for a clinical test.

Preeclampsia remains a leading cause of maternal and perinatal morbidity and mortality. Accurate prediction of preeclampsia risk would enable more effective, risk-based prenatal care pathways. Current risk assessment algorithms depend on clinical risk factors largely unavailable for first-time pregnant women. Delivering accurate preeclampsia risk assessment to this cohort of women, therefore requires for novel biomarkers. Here, we evaluated the relevance of metabolite biomarker candidates for their selection into a prototype rapid, quantitative Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) based clinical screening assay. First, a library of targeted LC-MS/MS assays for metabolite biomarker candidates was developed, using a medium-throughput translational metabolomics workflow, to verify biomarker potential in the Screening-for-Pregnancy-Endpoints (SCOPE, European branch) study. A variable pre-selection step was followed by the development of multivariable prediction models for pre-defined clinical use cases, i.e., prediction of preterm preeclampsia risk and of any preeclampsia risk. Within a large set of metabolite biomarker candidates, we confirmed the potential of dilinoleoyl-glycerol and heptadecanoyl-2-hydroxy-sn-glycero-3-phosphocholine to effectively complement Placental Growth Factor, an established preeclampsia biomarker, for the prediction of preeclampsia risk in first-time pregnancies without overt risk factors. These metabolites will be considered for integration in a prototype rapid, quantitative LC-MS/MS assay, and subsequent validation in an independent cohort