It’s not just about ‘more’. A research project exploring satisfaction with opportunities to play, for children in two Welsh neighbouring communities

This paper discusses a research project undertaken during spring 2014, in response to the findings of the Play Sufficiency Assessment in one Welsh Local Authority. The results highlighted anomalous findings between two neighbouring communities regarding the children’s self-reported levels of satisfaction with opportunities to play. The research study aimed to identify factors which may have caused the disparity in satisfaction between the two communities. The findings of the research indicate that simply having more places to play is not automatically an indicator of satisfaction. Factors such as child and parental fear, socio-economic conditions and the development of a ‘play culture’ within communities have a more significant role in influencing children’s freedom and opportunities to play

Mantle melting and intraplate volcanism due to self‐buoyant hydrous upwellings from the stagnant slab that are conveyed by small‐scale convection

The mechanisms sustaining basaltic continental intraplate volcanism remain controversial. Continental intraplate volcanism is often geographically associated with slab stagnation in the mantle transition zone (MTZ), for example, in eastern Asia, central Europe, and western North America. Using 2‐D geodynamic models, we here explore the role of the stagnation of a slab and an associated hydrous layer in the MTZ on the formation and evolution of intraplate volcanism. Due to the intrinsic buoyancy of the hydrous layer atop the stagnant slab, upwellings develop within a few million years and rise to ~410‐km depth. At these depths, they partly lose their intrinsic buoyancy due to dehydration and stall intermittently. However, they are readily entrained by sublithospheric small‐scale convection to reach the base of lithosphere, sustaining mantle melting and intraplate volcanism. Water contents of >0.3 wt.‐% in a ≥ 60‐km‐thick layer atop the slab are sufficient for an early (<~20 Myr) onset of melting to account for volcanism, for example, in NE China. Thus, significant amounts of hydrous materials are not expected to remain stable in the MTZ for geological timescales, consistent with geophysical estimates. To explain the geochemical signatures of the Cenozoic basaltic volcanism in northern China, a mixed composition of the hydrous layer, including an enriched mantle‐type and a hybrid depleted mid‐ocean ridge basalts mantle/high μ‐type component, is required

Transductive Learning with String Kernels for Cross-Domain Text Classification

For many text classification tasks, there is a major problem posed by the lack of labeled data in a target domain. Although classifiers for a target domain can be trained on labeled text data from a related source domain, the accuracy of such classifiers is usually lower in the cross-domain setting. Recently, string kernels have obtained state-of-the-art results in various text classification tasks such as native language identification or automatic essay scoring. Moreover, classifiers based on string kernels have been found to be robust to the distribution gap between different domains. In this paper, we formally describe an algorithm composed of two simple yet effective transductive learning approaches to further improve the results of string kernels in cross-domain settings. By adapting string kernels to the test set without using the ground-truth test labels, we report significantly better accuracy rates in cross-domain English polarity classification.Comment: Accepted at ICONIP 2018. arXiv admin note: substantial text overlap with arXiv:1808.0840

Exercise-based cardiac rehabilitation for adults with stable angina (review)

This is the final version of the article. Available from Cochrane Collaboration via the DOI in this record.BACKGROUND: A previous Cochrane review has shown that exercise-based cardiac rehabilitation (CR) can benefit myocardial infarction and post-revascularisation patients. However, the impact on stable angina remains unclear and guidance is inconsistent. Whilst recommended in the guidelines of American College of Cardiology/American Heart Association and the European Society of Cardiology, in the UK the National Institute for Health and Care Excellence (NICE) states that there is "no evidence to suggest that CR is clinically or cost-effective for managing stable angina". OBJECTIVES: To assess the effects of exercise-based CR compared to usual care for adults with stable angina. SEARCH METHODS: We updated searches from the previous Cochrane review 'Exercise-based cardiac rehabilitation for patients with coronary heart disease' by searching the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, DARE, CINAHL and Web of Science on 2 October 2017. We searched two trials registers, and performed reference checking and forward-citation searching of all primary studies and review articles, to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with a follow-up period of at least six months, which compared structured exercise-based CR with usual care for people with stable angina. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the risk of bias and extracted data according to the Cochrane Handbook for Systematic Reviews of Interventions. Two review authors also independently assessed the quality of the evidence using GRADE principles and we presented this information in a 'Summary of findings' table. MAIN RESULTS: Seven studies (581 participants) met our inclusion criteria. Trials had an intervention length of 6 weeks to 12 months and follow-up length of 6 to 12 months. The comparison group in all trials was usual care (without any form of structured exercise training or advice) or a no-exercise comparator. The mean age of participants within the trials ranged from 50 to 66 years, the majority of participants being male (range: 74% to 100%). In terms of risk of bias, the majority of studies were unclear about their generation of the randomisation sequence and concealment processes. One study was at high risk of detection bias as it did not blind its participants or outcome assessors, and two studies had a high risk of attrition bias due to the numbers of participants lost to follow-up. Two trials were at high risk of outcome reporting bias. Given the high risk of bias, small number of trials and participants, and concerns about applicability, we downgraded our assessments of the quality of the evidence using the GRADE tool.Due to the very low-quality of the evidence base, we are uncertain about the effect of exercise-based CR on all-cause mortality (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.18 to 5.67; 195 participants; 3 studies; very low-quality evidence), acute myocardial infarction (RR 0.33, 95% CI 0.07 to 1.63; 254 participants; 3 studies; very low-quality evidence) and cardiovascular-related hospital admissions (RR 0.14, 95% CI 0.02 to 1.1; 101 participants; 1 study; very low-quality evidence). We found low-quality evidence that exercise-based CR may result in a small improvement in exercise capacity compared to control (standardised mean difference (SMD) 0.45, 95% CI 0.20 to 0.70; 267 participants; 5 studies, low-quality evidence). We were unable to draw conclusions about the impact of exercise-based CR on quality of life (angina frequency and emotional health-related quality-of-life score) and CR-related adverse events (e.g. skeletomuscular injury, cardiac arrhythmia), due to the very low quality of evidence. No data were reported on return to work. AUTHORS' CONCLUSIONS: Due to the small number of trials and their small size, potential risk of bias and concerns about imprecision and lack of applicability, we are uncertain of the effects of exercise-based CR compared to control on mortality, morbidity, cardiovascular hospital admissions, adverse events, return to work and health-related quality of life in people with stable angina. Low-quality evidence indicates that exercise-based CR may result in a small increase in exercise capacity compared to usual care. High-quality, well-reported randomised trials are needed to assess the benefits and harms of exercise-based CR for adults with stable angina. Such trials need to collect patient-relevant outcomes, including clinical events and health-related quality of life. They should also assess cost-effectiveness, and recruit participants that are reflective of the real-world population of people with angina.University of Exeter Medical School, UK. The Cochrane Heart Group US Satellite is supported by intramural support from the Northwestern University Feinberg School of Medicine and the Northwestern University Clinical and Translational Science (NUCATS) Institute (UL1TR000150)., USA. This project was supported by the National Institute for Health Research, via Cochrane Incentive funding to the Heart Group

Validation of Global EUV Wave MHD Simulations and Observational Techniques

Global EUV waves remain a controversial phenomenon more than 20 yr after their discovery by SOHO/EIT. Although consensus is growing in the community that they are most likely large-amplitude waves or shocks, the wide variety of observations and techniques used to identify and analyze them have led to disagreements regarding their physical properties and interpretation. Here, we use a 3D magnetohydrodynamic (MHD) model of the solar corona to simulate an EUV wave event on 2009 February 13 to enable a detailed validation of the various commonly used detection and analysis techniques of global EUV waves. The simulated event exhibits comparable behavior to that of a real EUV wave event, with similar kinematic behavior and plasma parameter evolution. The kinematics of the wave are estimated via visual identification and profile analysis, with both approaches providing comparable results. We find that projection effects can affect the derived kinematics of the wave, due to the variation in fast-mode wave speed with height in the corona. Coronal seismology techniques typically used for estimates of the coronal magnetic field are also tested and found to estimate fast-mode speeds comparable to those of the model. Plasma density and temperature variations of the wave front are also derived using a regularized inversion approach and found to be consistent with observed wave events. These results indicate that global waves are best interpreted as large-amplitude waves and that they can be used to probe the coronal medium using well-defined analysis techniques

Structural reliability analysis of multiple limit state functions using multi-input multi-output support vector machine

Selecting and using an appropriate structural reliability method is critical for the success of structural reliability analysis and reliability-based design optimization. However, most of existing structural reliability methods are developed and designed for a single limit state function and few methods can be used to simultaneously handle multiple limit state functions in a structural system when the failure probability of each limit state function is of interest, for example, in a reliability-based design optimization loop. This article presents a new method for structural reliability analysis with multiple limit state functions using support vector machine technique. A sole support vector machine surrogate model for all limit state functions is constructed by a multi-input multi-output support vector machine algorithm. Furthermore, this multi-input multi-output support vector machine surrogate model for all limit state functions is only trained from one data set with one calculation process, instead of constructing a series of standard support vector machine models which has one output only. Combining the multi-input multi-output support vector machine surrogate model with direct Monte Carlo simulation, the failure probability of the structural system as well as the failure probability of each limit state function corresponding to a failure mode in the structural system can be estimated. Two examples are used to demonstrate the accuracy and efficiency of the presented method

How early can myocardial iron overload occur in Beta thalassemia major?

BACKGROUND: Myocardial siderosis is the most common cause of death in patients with beta thalassemia major(TM). This study aimed at investigating the occurrence, prevalence and severity of cardiac iron overload in a young Chinese population with beta TM. METHODS AND RESULTS: We analyzed T2* cardiac magnetic resonance (CMR), left ventricular ejection fraction (LVEF) and serum ferritin (SF) in 201 beta TM patients. The median age was 9 years old. Patients received an average of 13 units of blood per year. The median SF level was 4536 ng/ml and 165 patients (82.1%) had SF>2500 ng/ml. Myocardial iron overload was detected in 68 patients (33.8%) and severe myocardial iron overload was detected in 26 patients (12.6%). Twenty-two patients ≤10 years old had myocardial iron overload, three of whom were only 6 years old. No myocardial iron overload was detected under the age of 6 years. Median LVEF was 64% (measured by CMR in 175 patients). Five of 6 patients with a LVEF<56% and 8 of 10 patients with cardiac disease had myocardial iron overload. CONCLUSIONS: The TM patients under follow-up at this regional centre in China patients are younger than other reported cohorts, more poorly-chelated, and have a high burden of iron overload. Myocardial siderosis occurred in patients younger than previously reported, and was strongly associated with impaired LVEF and cardiac disease. For such poorly-chelated TM patients, our data shows that the first assessment of cardiac T2* should be performed as early as 6 years old

DRAM-3 modulates autophagy and promotes cell survival in the absence of glucose

Macroautophagy is a membrane-trafficking process that delivers cytoplasmic constituents to lysosomes for degradation. The process operates under basal conditions as a mechanism to turnover damaged or misfolded proteins and organelles. As a result, it has a major role in preserving cellular integrity and viability. In addition to this basal function, macroautophagy can also be modulated in response to various forms of cellular stress, and the rate and cargoes of macroautophagy can be tailored to facilitate appropriate cellular responses in particular situations. The macroautophagy machinery is regulated by a group of evolutionarily conserved autophagy-related (ATG) proteins and by several other autophagy regulators, which either have tissue-restricted expression or operate in specific contexts. We report here the characterization of a novel autophagy regulator that we have termed DRAM-3 due to its significant homology to damage-regulated autophagy modulator (DRAM-1). DRAM-3 is expressed in a broad spectrum of normal tissues and tumor cells, but different from DRAM-1, DRAM-3 is not induced by p53 or DNA-damaging agents. Immunofluorescence studies revealed that DRAM-3 localizes to lysosomes/autolysosomes, endosomes and the plasma membrane, but not the endoplasmic reticulum, phagophores, autophagosomes or Golgi, indicating significant overlap with DRAM-1 localization and with organelles associated with macroautophagy. In this regard, we further proceed to show that DRAM-3 expression causes accumulation of autophagosomes under basal conditions and enhances autophagic flux. Reciprocally, CRISPR/Cas9-mediated disruption of DRAM-3 impairs autophagic flux confirming that DRAM-3 is a modulator of macroautophagy. As macroautophagy can be cytoprotective under starvation conditions, we also tested whether DRAM-3 could promote survival on nutrient deprivation. This revealed that DRAM-3 can repress cell death and promote long-term clonogenic survival of cells grown in the absence of glucose. Interestingly, however, this effect is macroautophagy-independent. In summary, these findings constitute the primary characterization of DRAM-3 as a modulator of both macroautophagy and cell survival under starvation conditions

Evaluation of two high-throughput proteomic technologies for plasma biomarker discovery in immunotherapy-treated melanoma patients

Background: Selective kinase and immune checkpoint inhibitors, and their combinations, have significantly improved the survival of patients with advanced metastatic melanoma. Not all patients will respond to treatment however, and some patients will present with significant toxicities. Hence, the identification of biomarkers is critical for the selection and management of patients receiving treatment. Biomarker discovery often involves proteomic techniques that simultaneously profile multiple proteins but few studies have compared these platforms. Methods: In this study, we used the multiplex bead-based Eve Technologies Discovery assay and the aptamer-based SomaLogic SOMAscan assay to identify circulating proteins predictive of response to immunotherapy in melanoma patients treated with combination immune checkpoint inhibitors. Expression of four plasma proteins were further validated using the bead-based Millipore Milliplex assay. Results: Both the Discovery and the SOMAscan assays detected circulating plasma proteins in immunotherapy-treated melanoma patients. However, these widely used assays showed limited correlation in relative protein quantification, due to differences in specificity and the dynamic range of protein detection. Protein data derived from the Discovery and Milliplex bead-based assays were highly correlated. Conclusions: Our study highlights significant limitations imposed by inconsistent sensitivity and specificity due to differences in the detection antibodies or aptamers of these widespread biomarker discovery approaches. Our findings emphasize the need to improve these technologies for the accurate identification of biomarkers