922017 research outputs found
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Exploring the Use and Delivery of School-Based Mindfulness Programmes for Young Children
No full textAims: This systematic literature review aimed to explore how school-based mindfulness programmes have been adapted for use with young children in education settings, from ages three to nine years old. Method: School-based mindfulness interventions were assessed on quality using qualitative and quantitative frameworks. Important attitudinal principles and practical components of the school-based mindfulness interventions were analysed. Findings: The results revealed vast heterogeneity across programme design and delivery. The majority of programmes used mindful movement, visuals/props, sensory activities, reflection on experiences and the use of metaphorical language to teach young children mindfulness. There appeared to be greater precedence for experiential practices than instructional practices such as attitudinal features. Mindfulness has been used mainly to support cognitive functioning, particularly attentional and executive functioning. Limitations: The COVID-19 pandemic has delayed submission of this article, meaning that the most recent research findings might not be documented. The heterogeneity of the studies made drawing conclusions difficult.Conclusions: Implications for educational psychology practice and areas for future research are considered, particularly in relation to how educational psychologists can work with teachers to deliver effective and sustainable mindfulness interventions.Keywords: mindfulness; attention; young children; intervention; education<br/
Looking into the IL-1 of the storm: Are inflammasomes the link between immunothrombosis and hyperinflammation in cytokine storm syndromes?
No full textInflammasomes and the interleukin (IL)-1 family of cytokines are key mediators of both inflammation and immunothrombosis. Inflammasomes are responsible for the release of the pro-inflammatory cytokines IL-1β and IL-18, as well as releasing tissue factor (TF), a pivotal initiator of the extrinsic coagulation cascade. Uncontrolled production of inflammatory cytokines results in what is known as a “cytokine storm” leading to hyperinflammatory disease. Cytokine storms can complicate a variety of diseases and results in hypercytokinemia, coagulopathies, tissue damage, multi-organ failure and death. Patients presenting with cytokine storm syndromes have a high mortality rate, driven in part by disseminated intravascular coagulation (DIC). Whilst our knowledge on the factors propagating cytokine storms is increasing, how cytokine storm influences DIC remains unknown, and therefore treatments for diseases, where these aspects are a key feature are limited, with most targeting specific cytokines. Currently, no therapies target the immunothrombosis aspect of hyperinflammatory syndromes. Here we discuss how targeting the inflammasome and pyroptosis may be a novel therapeutic strategy for the treatment of hyperinflammation and its associated pathologies
Concurrent multi-scale modeling of granular materials: Role of coarse-graining in FEM-DEM coupling
No full textThe finite element method (FEM) is commonly used for modeling continuum media, while particle simulation methods like the so-called discrete element method (DEM) are used for discrete systems. Coupling the discrete (DEM) and continuum (FEM) methods is conventionally achieved through a direct mapping between discrete particles and finite elements. Coarse-graining (CG) is a micro-macro transition method (discrete to continuum) that maps discrete particle data onto smooth, differentiable fields that satisfy the continuum equations. By choosing an appropriate length scale (the coarse-graining width c), the coarse-grained fields are then homogenized and projected onto a FEM spatial discretization.This concept is utilized here to reformulate FEM-DEM coupling methods, both surface and volume, where in the limiting case of c → 0, the classical coupling is recovered. For surface coupling, the discrete particle-surface contact forces are first mapped onto a continuous surface traction field (using CG) which is then coupled to the continuum FEM model. For volume coupling (also known as the Arlequin framework), the homogenization operators are enriched with CG functions, offering a non-local coupling approach between discrete particles, their continuum fields, and the finite element formulation.The CG enrichment represents a new strategy that consists of (1) a particle-to-continuum mapping and (2) a continuum-to-continuum coupling based on “CG-enriched homogenization” (CGH). It is shown for surface coupling that the CG-enriched formulation not only leads to more accurate results, conserving symmetry, but also reduces energies generated by the coupling. For volume coupling, there is consistently less numerical dissipation with than without CG-enrichment, especially when the load contains high-frequency content. Finally, the optimal CG widths are identified for very simple test cases, with which the surface/volume coupling performs best.CGH can be potentially extended beyond the present examples, by considering other continuum fields (e.g., higher-order) and equations (e.g., multi-physics), and used to formulate other concurrent multi-scale modeling methods
Structural insights into UbiD reversible decarboxylation
No full textThe ubiquitous UbiX-UbiD system is associated with a wide range of microbial (de)carboxylation reactions. Recent X-ray crystallographic studies have contributed to elucidating the enigmatic mechanism underpinning the conversion of α,β-unsaturated acids by this system. The UbiD component utilises a unique cofactor, prenylated flavin (prFMN), generated by the bespoke action of the associated UbiX flavin prenyltransferase. Structure determination of a range of UbiX/UbiD representatives has revealed a generic mode of action for both the flavin-to-prFMN metamorphosis and the (de)carboxylation. In contrast to the conserved UbiX, the UbiD superfamily is associated with a versatile substrate range. The latter is reflected in the considerable variety of UbiD quaternary structure, dynamic behaviour and active site architecture. Directed evolution of UbiD enzymes has taken advantage of this apparent malleability to generate new variants supporting in vivo hydrocarbon production. Other applications include coupling UbiD to carboxylic acid reductase to convert alkenes into α,β-unsaturated aldehydes via enzymatic CO2 fixation.<br/
Should Developing Countries Ban Dual Practice by physicians? An Analysis Under Mixed Hospital Competition*
No full textDual practice, where physicians work both in public and private hospitals, is a widely observed phenomenon, particularly in developing countries. This paper studies a multi-stage game where hospitals compete for physicians as well as patients and, the effort provided by physicians endogenously depends on the competitive setting in which hospitals operate. Specifically, we examine the impact of allowing dual practice on hospital payoffs, physician effort and patients and societal welfare. We find that dual practice introduced in a setting that resembles the characteristics of the health care system of a developing country can be in general socially desirable, since it softens the competition for physician’s exclusive effort (reducing hospital costs) while also increasing the level of their medical effort.<br/
Improving the environmental sustainability of polyketides colorants production by Talaromyces strain through better hydrodynamic design in bioreactors
No full textOne important step towards the commercialization of microbial-derived colorants is the reproducibility of the cultivation stage in bench-scale bioreactors as well as improving the hydrodynamic design in bioreactors. Aiming to address these technical barriers, Talaromyces amestolkiae was cultivated in a 4-L stirred-tank bioreactor using two types of impellers (Rushton turbine (RT) and Elephant ear (EE) impellers) and aeration modes (cascading and constant airflow), to assess their effects on red colorant production. The results showed that EE under constant airflow (4.0 Lmin-1) promoted the maximum red colorant formation (28.7 UA500nm), thus improving the reproducibility of the process. The volumetric oxygen transfer coefficient of culture broth was correlated to cell morphology, which was a result of impeller geometry of EE through the shear conditions impacting the fungi cells. The hairy pellet morphology favored nutrient and oxygen uptake and allowed an improvement in the colorant’s synthesis. Life cycle assessment was also carried out to identify opportunities for improving the best process design from an environmental sustainability perspective. For example, the total climate change and primary energy demand were estimated at 31.11 kg CO2 eq./g red colorant and 830.7 MJ/g red colorant, respectively, with the cultivation stage contributing with 65% and 63% of these impacts. The electricity consumption was identified as the main hotspot in this stage, a trend that was observed across all other impact categories. This can be improved by optimizing cultivation lengths combined with the use of low carbon electricity sources. These findings ensure a step forward towards the scaling-up at industrial scale of the T. amestolkiae cultivation for the production of bio-based colorants in an environmentally sustainable way
ALBI grade predicts suitability for further systemic therapy following sorafenib in patients with advanced hepatocellular carcinoma.
No full textBackground & Aims: Preserved performance status (PS) and liver function are required for systemic therapy in patients with advanced hepatocellular carcinoma (aHCC). We investigated the frequency of suitability for further systemic therapies following sorafenib in aHCC.Methods: Demographic, tumour, and therapy-related data were collected retrospectively for patients with aHCC who received sorafenib at a UK tertiary referral centre (training cohort), and an independent French centre (validation cohort). The primary end point was percentage of patients with Child-Pugh class A (CP-A) liver disease and PS 0-1 after sorafenib discontinuation.Results: Sorafenib was received by 182 patients. After sorafenib discontinuation, 93 patients (51%) were CP-A and 60 patients (33%) were PS 0-1; 43 patients (24%) were both CP-A and PS 0-1. On multivariable analysis, patients with Albumin-Bilirubin (ALBI) score of 1 at time of sorafenib commencement were more likely to be suitable for post-sorafenib therapy, (44% grade 1 vs 15% grade 2) (OR 3.76, 95%CI 1.72-8.25, p=0.0009). In the validation cohort of 216 patients baseline ALBI grade was also significantly associated with suitability for further systemic therapy (p=0.008). Conclusions: Most patients with aHCC are not suitable for further systemic therapy after sorafenib, but those with ALBI grade 1 have a greater likelihood of suitability.<br/
THE AVOIDING LATE DIAGNOSIS OF OVARIAN CANCER (ALDO) PROJECT; A PILOT NATIONAL SURVEILLANCE PROGRAM FOR WOMEN WITH PATHOGENIC GERMLINE VARIANTS IN BRCA1 AND BRCA2.
No full textBackgrounds To establish ‘real-world’ performance and cost-effectiveness of Ovarian Cancer (OC) surveillance in women with pathogenic germline BRCA1/2 variants deferring risk-reducing salpingo-oophorectomy (RRSO). Methods875 female BRCA1/2-heterozygotes were recruited at 13 UK centres and via an online media campaign, with 767 undergoing at least one 4-monthly surveillance test with the Risk of Ovarian Cancer Algorithm (ROCA® Test). Surveillance performance was calculated with modelling of occult cancers detected at RRSO. Incremental cost-effectiveness ratio (ICER) was calculated using Markov population cohort simulation. Results 8 OCs occurred during 1277 women screen years: 2 occult OCs at RRSO (both stage 1a), and 6 screen-detected; 3 of 6 (50%) were ≤stage 3a and 5 of 6 (83%) were completely surgically cytoreduced. Modelled sensitivity, specificity, PPV and NPV for OC were 87.5% (95%CI, 47.3-99.7), 99.9% (99.9-100), 75% (34.9-96.8) and 99.9% (99.9-100) respectively. The predicted number of quality-adjusted life-years gained by surveillance was 0.179 with an ICER cost-saving of -£102,496/QALY. ConclusionOC surveillance for women deferring RRSO in a ‘real-world’ setting is feasible and demonstrates similar performance to research trials; it down-stages OC, leading to a high complete cytoreduction rate and is cost-saving in the UK setting. Whilst RRSO remains recommended management, ROCA-based surveillance may be considered for BRCA-heterozygotes deferring such surgery
Does the design of the NHS Low Calorie Diet Programme have fidelity to the programme specification? A documentary review of service parameters and behaviour change content in a Type 2 Diabetes intervention
No full textBackgroundNHS England commissioned four independent service providers to pilot low-calorie diet programmes to drive weight loss, improve glycaemia and potentially achieve remission of Type 2 Diabetes across 10 localities. Intervention fidelity might contribute to programme success. Previous research has illustrated a drift in fidelity in the design and delivery of other national diabetes programmes.Aims: 1) To describe and compare the programme designs across the four service providers; 2) To assess the fidelity of programme designs to the NHS England service specification.MethodsThe NHS England service specification documents and each provider’s programme design documents were double coded for key intervention content using the Template for Intervention Description and Replication Framework and the Behaviour Change Technique (BCT) Taxonomy. ResultsThe four providers demonstrated fidelity to most but not all the service parameters stipulated in the NHS England service specification. Providers included between 74% and 87% of the 23 BCTs identified in the NHS specification. Twelve of these BCTs were included by all four providers; two BCTs were consistently absent. An additional seven to 24 BCTs were included across providers. ConclusionsA loss of fidelity for some service parameters and BCTs was identified across the provider’s designs; this may have important consequences for programme delivery and thus programme outcomes. Furthermore, there was a large degree of variation between providers in the presence and dosage of additional BCTs. How these findings relate to the fidelity of programme delivery and variation in programme outcomes and experiences across providers will be examined.KeywordsType 2 diabetes, low calorie diet, behaviour change, intervention design, intervention fidelity, total diet replacement, weight management <br/
How Cosmic Rays Mediate the Evolution of the Interstellar Medium
No full textWe explore the impact of diffusive cosmic rays (CRs) on the evolution of the interstellar medium (ISM) under varying assumptions of supernova explosion environment. In practice, we systematically vary the relative fractions of supernovae (SN) occurring in star-forming high-density gas and those occurring in random locations decoupled from star-forming gas to account for SN from run-away stars or explosions in regions that have been cleared by prior SN, stellar winds, or radiation. We explore various mixed models by adjusting these fractions relative to each other. We find that in the simple system of a periodic stratified gas layer the ISM structure will evolve to one of two solutions: a "peak driving" state where warm gas is volume filling or a "thermal runaway" state where hot gas is volume filling. CR pressure and transport are important factors that strongly influence the solution state the ISM reaches and have the ability to flip the ISM between solutions. Observable signatures such as gamma ray emission and HI gas are explored. We find that gamma ray luminosity from pion decay is largely consistent with observations for a range of model parameters. The thickness of the HI gas layer may be too compact, however, this may be due to a large cold neutral fraction of midplane gas. The volume fraction of hot gas evolves to stable states in both solutions, but neither settles to a Milky Way-like configuration, suggesting that additional physics which is omitted here (e.g. a cosmological circum-galactic medium, radiation transport, or spectrally resolved and spatially varying CR transport) may be required