Newcastle University

About: Newcastle University is a education organization based out in Newcastle upon Tyne, United Kingdom. It is known for research contribution in the topics: Population & Context (language use). The organization has 31772 authors who have published 71187 publications receiving 2539147 citations. The organization is also known as: University of Newcastle upon Tyne.

Endoglin promotes endothelial cell proliferation and TGF‐β/ALK1 signal transduction

Abstract: Endoglin is a transmembrane accessory receptor for transforming growth factor-β (TGF-β) that is predominantly expressed on proliferating endothelial cells in culture and on angiogenic blood vessels in vivo. Endoglin, as well as other TGF-β signalling components, is essential during angiogenesis. Mutations in endoglin and activin receptor-like kinase 1 (ALK1), an endothelial specific TGF-β type I receptor, have been linked to the vascular disorder, hereditary haemorrhagic telangiectasia. However, the function of endoglin in TGF-β/ALK signalling has remained unclear. Here we report that endoglin is required for efficient TGF-β/ALK1 signalling, which indirectly inhibits TGF-β/ALK5 signalling. Endothelial cells lacking endoglin do not grow because TGF-β/ALK1 signalling is reduced and TGF-β/ALK5 signalling is increased. Surviving cells adapt to this imbalance by downregulating ALK5 expression in order to proliferate. The ability of endoglin to promote ALK1 signalling also explains why ectopic endoglin expression in endothelial cells promotes proliferation and blocks TGF-β-induced growth arrest by indirectly reducing TGF-β/ALK5 signalling. Our results indicate a pivotal role for endoglin in the balance of ALK1 and ALK5 signalling to regulate endothelial cell proliferation.

The efficacy of preemptive analgesia for acute postoperative pain management: a meta-analysis.

Abstract: Whether preemptive analgesic interventions are more effective than conventional regimens in managing acute postoperative pain remains controversial. We systematically searched for randomized controlled trials that specifically compared preoperative analgesic interventions with similar postoperative analgesic interventions via the same route. The retrieved reports were stratified according to five types of analgesic interventions: epidural analgesia, local anesthetic wound infiltration, systemic N-methyl-d-aspartic acid (NMDA) receptor antagonists, systemic nonsteroidal antiinflammatory drugs (NSAIDs), and systemic opioids. The primary outcome measures analyzed were the pain intensity scores, supplemental analgesic consumption, and time to first analgesic consumption. Sixty-six studies with data from 3261 patients were analyzed. Data were combined by using a fixed-effect model, and the effect size index (ES) used was the standardized mean difference. When the data from all three outcome measures were combined, the ES was most pronounced for preemptive administration of epidural analgesia (ES, 0.38; 95% confidence interval [CI], 0.28-0.47), local anesthetic wound infiltration (ES, 0.29; 95% CI, 0.17-0.40), and NSAID administration (ES, 0.39; 95% CI, 0.27-0.48). Whereas preemptive epidural analgesia resulted in consistent improvements in all three outcome variables, preemptive local anesthetic wound infiltration and NSAID administration improved analgesic consumption and time to first rescue analgesic request, but not postoperative pain scores. The least proof of efficacy was found in the case of systemic NMDA antagonist (ES, 0.09; 95% CI, -0.03 to 0.22) and opioid (ES, -0.10; 95% CI, -0.26 to 0.07) administration, and the results remain equivocal.

An empirical analysis of self‐employment in the U.K.

Abstract: The paper formulates a self-employment/paid-employment choice problem that draws upon Knight's notion that the individual responds to the risk-adjusted relative earnings opportunities in each sector. Based on a development of such choice-theoretic considerations, an econometric model is developed with the purpose of empirically examining the determinants of self-employment. The model features simultaneous determination of employment status and earnings, which allows for self-selectivity. The model is estimated using a sample of 4762 individuals from the General Household Survey for 1978. The estimation of the earnings equation enables a calculation of the self-employment/paid-employment earnings differential and the estimated probit equation for self-employment/paid-employment status facilitates the prediction of the probability of self-employment. The paper finds that there is positive selection bias in the observed earnings of employees, that the probability of self-employment depends positively on the earnings difference between the two sectors and that education and age are significant determinants of self-employment.

Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways

Abstract: Genome-wide association studies (GWAS) of psychiatric disorders have identified multiple genetic associations with such disorders, but better methods are needed to derive the underlying biological mechanisms that these signals indicate. We sought to identify biological pathways in GWAS data from over 60,000 participants from the Psychiatric Genomics Consortium. We developed an analysis framework to rank pathways that requires only summary statistics. We combined this score across disorders to find common pathways across three adult psychiatric disorders: schizophrenia, major depression and bipolar disorder. Histone methylation processes showed the strongest association, and we also found statistically significant evidence for associations with multiple immune and neuronal signaling pathways and with the postsynaptic density. Our study indicates that risk variants for psychiatric disorders aggregate in particular biological pathways and that these pathways are frequently shared between disorders. Our results confirm known mechanisms and suggest several novel insights into the etiology of psychiatric disorders.