The study of progesterone action in human myometrial explants

Study hypothesis: Myometrial explants represent a superior model compared with cell culture models for the study of human myometrial progesterone (P4) signalling in parturition. Study finding: Gene expression analysis showed myometrial explants closely resemble the in vivo condition and the anti-inflammatory action of P4 is not lost with labour onset. What is known already: Circulating P4 levels decline before the onset of parturition in most animals, but not in humans. This has led to the suggestion that there is a functional withdrawal of P4 action at the myometrial level prior to labour onset. However, to date, no evidence of a loss of P4 function has been provided, with studies hampered by a lack of a physiologically relevant model. Study design, samples/materials, methods: Myometrial biopsies obtained at Caesarean section were dissected into explants after a portion was immediately snap frozen (t = 0). Microarray analysis was used to compare gene expression of t = 0 with paired (i) explants, (ii) passage 4 myometrial cell cultures or (iii) the hTERT myometrial cell line. Western blotting and chemokine/cytokine assays were used to study P4 signalling in myometrial explants. Main results and the role of chance: Gene expression comparison of t = 0 to the three models demonstrated that explants more closely resemble the in vivo status. At the protein level, explants maintain both P4 receptor (PR) and glucocorticoid receptor (GR) levels versus t = 0 whereas cells only maintain GR levels. Additionally, treatment with 1 μM P4 led to a reduction in interleukin-1 (IL-1) β-driven cyclooxygenase-2 in explants but not in cells. P4 signalling in explants was PR-mediated and associated with a repression of p65 and c-Jun phosphorylation. Furthermore, the anti-inflammatory action of P4 was maintained after labour onset. Limitations/reasons for caution: There is evidence of basal inflammation in the myometrial explant model. Wider implications of the findings: Myometrial explants constitute a novel model to study P4 signalling in the myometrium and can be used to further elucidate the mechanisms of P4 action in human labour. Large scale data: Data deposited at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=gvmpggkurbgxfqf&acc=GSE77830

Dynamic Scaling and Two-Dimensional High-Tc Superconductors

There has been ongoing debate over the critical behavior of two-dimensional superconductors; in particular for high Tc superconductors. The conventional view is that a Kosterlitz-Thouless-Berezinskii transition occurs as long as finite size effects do not obscure the transition. However, there have been recent suggestions that a different transition actually occurs which incorporates aspects of both the dynamic scaling theory of Fisher, Fisher, and Huse and the Kosterlitz-Thouless-Berezinskii transition. Of general interest is that this modified transition apparently has a universal dynamic critical exponent. Some have countered that this apparent universal behavior is rooted in a newly proposed finite-size scaling theory; one that also incorporates scaling and conventional two-dimensional theory. To investigate these issues we study DC voltage versus current data of a 12 angstrom thick YBCO film. We find that the newly proposed scaling theories have intrinsic flexibility that is relevant to the analysis of the experiments. In particular, the data scale according to the modified transition for arbitrarily defined critical temperatures between 0 K and 19.5 K, and the temperature range of a successful scaling collapse is related directly to the sensitivity of the measurement. This implies that the apparent universal exponent is due to the intrinsic flexibility rather than some real physical property. To address this intrinsic flexibility, we propose a criterion which would give conclusive evidence for phase transitions in two-dimensional superconductors. We conclude by reviewing results to see if our criterion is satisfied.Comment: 14 page

Wikipedia as informal self-education for clinical decision-making in medical practice

Background For almost any topic, a Wikipedia page will appear among the first ten items of a search online. Wikipedia is also a site whose quality and reliability has been called into question. Methods In this paper, we aim to discuss medical practitioners’ use of Wikipedia, what this consists of and what it might be. We consider the context and history of Wikipedia before discussing the relationship between Wikipedia and the medical profession. In so doing, we will consider Wikipedia as a means of informal self-education and the extent to which it might inform clinical decision-making. We compare with the existing literature results from our two small-scale empirical studies of Wikipedia and clinical decision-making. Results Notwithstanding issues over quality and reliability, Wikipedia’s rules on verifiability are such that its articles are very heavily referenced, and this is just as true of health-related articles. The Cochrane/Wikipedia Initiative in improving the quality and reliability of medical and health pages in Wikipedia is significant in increasing reliability. Our respondents largely concurred with the results from earlier studies on the use of Wikipedia by medical practitioners. Conclusion Perhaps the very doubt over Wikipedia’s accuracy is its greatest strength as a means of informal education of doctors. That medical and health articles on Wikipedia can be so fully referenced and still be doubted is arguably a good thing and one whose effects may be spread into other, more trusted, publications. Hence, one might envisage a future where no one source is taken automatically on trust. Keywords Wikipedia, informal education, continued professional development, medical education

Phenomenology of the Lense-Thirring effect in the Solar System

Recent years have seen increasing efforts to directly measure some aspects of the general relativistic gravitomagnetic interaction in several astronomical scenarios in the solar system. After briefly overviewing the concept of gravitomagnetism from a theoretical point of view, we review the performed or proposed attempts to detect the Lense-Thirring effect affecting the orbital motions of natural and artificial bodies in the gravitational fields of the Sun, Earth, Mars and Jupiter. In particular, we will focus on the evaluation of the impact of several sources of systematic uncertainties of dynamical origin to realistically elucidate the present and future perspectives in directly measuring such an elusive relativistic effect.Comment: LaTex, 51 pages, 14 figures, 22 tables. Invited review, to appear in Astrophysics and Space Science (ApSS). Some uncited references in the text now correctly quoted. One reference added. A footnote adde

Early mobilisation versus plaster immobilisation of simple elbow dislocations: Results of the FuncSiE multicentre randomised clinical trial

Background/aim To compare outcome of early mobilisation and plaster immobilisation in patients with a simple elbow dislocation. We hypothesised that early mobilisation would result in earlier functional recovery. Methods From August 2009 to September 2012, 100 adult patients with a simple elbow dislocation were enrolled in this multicentre randomised controlled trial. Patients were randomised to early mobilisation (n=48) or 3 weeks plaster immobilisation (n=52). Primary outcome measure was the Quick Disabilities of the Arm, Shoulder, and Hand (Quick-DASH) score. Secondary outcomes were the Oxford Elbow Score, Mayo Elbow Performance Index, pain, range of motion, complications and activity resumption. Patients were followed for 1 year. Results Quick-DASH scores at 1 year were 4.0 (95% CI 0.9 to 7.1) points in the early mobilisation group versus 4.2 (95% CI 1.2 to 7.2) in the plaster immobilisation group. At 6 weeks, early mobilised patients reported less disability (Quick-DASH 12 (95% CI 9 to 15) points vs 19 (95% CI 16 to 22); p<0.05) and had a larger arc of flexion and extension (121° (95% CI 115° to 127°) vs 102° (95% CI 96° to 108°); p<0.05). Patients returned to work sooner after early mobilisation (10 vs 18 days; p=0.020). Complications occurred in 12 patients; this was unrelated to treatment. No recurrent dislocations occurred. Conclusions Early active mobilisation is a safe and effective treatment for simple elbow dislocations. Patients recovered faster and returned to work earlier without increasing the complication rate. No evidence was found supporting treatment benefit at 1 year

Evaluation of presumably disease causing SCN1A variants in a cohort of common epilepsy syndromes

Objective: The SCN1A gene, coding for the voltage-gated Na+ channel alpha subunit NaV1.1, is the clinically most relevant epilepsy gene. With the advent of high-throughput next-generation sequencing, clinical laboratories are generating an ever-increasing catalogue of SCN1A variants. Variants are more likely to be classified as pathogenic if they have already been identified previously in a patient with epilepsy. Here, we critically re-evaluate the pathogenicity of this class of variants in a cohort of patients with common epilepsy syndromes and subsequently ask whether a significant fraction of benign variants have been misclassified as pathogenic. Methods: We screened a discovery cohort of 448 patients with a broad range of common genetic epilepsies and 734 controls for previously reported SCN1A mutations that were assumed to be disease causing. We re-evaluated the evidence for pathogenicity of the identified variants using in silico predictions, segregation, original reports, available functional data and assessment of allele frequencies in healthy individuals as well as in a follow up cohort of 777 patients. Results and Interpretation: We identified 8 known missense mutations, previously reported as path

Machine learning algorithms performed no better than regression models for prognostication in traumatic brain injury

Objective: We aimed to explore the added value of common machine learning (ML) algorithms for prediction of outcome for moderate and severe traumatic brain injury. Study Design and Setting: We performed logistic regression (LR), lasso regression, and ridge regression with key baseline predictors in the IMPACT-II database (15 studies, n = 11,022). ML algorithms included support vector machines, random forests, gradient boosting machines, and artificial neural networks and were trained using the same predictors. To assess generalizability of predictions, we performed internal, internal-external, and external validation on the recent CENTER-TBI study (patients with Glasgow Coma Scale <13, n = 1,554). Both calibration (calibration slope/intercept) and discrimination (area under the curve) was quantified. Results: In the IMPACT-II database, 3,332/11,022 (30%) died and 5,233(48%) had unfavorable outcome (Glasgow Outcome Scale less than 4). In the CENTER-TBI study, 348/1,554(29%) died and 651(54%) had unfavorable outcome. Discrimination and calibration varied widely between the studies and less so between the studied algorithms. The mean area under the curve was 0.82 for mortality and 0.77 for unfavorable outcomes in the CENTER-TBI study. Conclusion: ML algorithms may not outperform traditional regression approaches in a low-dimensional setting for outcome prediction after moderate or severe traumatic brain injury. Similar to regression-based prediction models, ML algorithms should be rigorously validated to ensure applicability to new populations

Measurement of the cross section for isolated-photon plus jet production in pp collisions at √s=13 TeV using the ATLAS detector

The dynamics of isolated-photon production in association with a jet in proton–proton collisions at a centre-of-mass energy of 13 TeV are studied with the ATLAS detector at the LHC using a dataset with an integrated luminosity of 3.2 fb−1. Photons are required to have transverse energies above 125 GeV. Jets are identified using the anti- algorithm with radius parameter and required to have transverse momenta above 100 GeV. Measurements of isolated-photon plus jet cross sections are presented as functions of the leading-photon transverse energy, the leading-jet transverse momentum, the azimuthal angular separation between the photon and the jet, the photon–jet invariant mass and the scattering angle in the photon–jet centre-of-mass system. Tree-level plus parton-shower predictions from Sherpa and Pythia as well as next-to-leading-order QCD predictions from Jetphox and Sherpa are compared to the measurements