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Impaired regulatory T cell control of astroglial overdrive and microglial pruning in schizophrenia
No full textIt is widely held that schizophrenia involves an active process of peripheral inflammation that induces or reflects brain inflammation with activation of microglia, the brain’s resident immune cells. However, recent in vivo radioligand binding studies and large-scale transcriptomics in post-mortem brain report reduced markers of microglial inflammation. The findings suggest a contrary hypothesis; that microglia are diverted into their non-inflammatory synaptic remodelling phenotype that interferes with neurodevelopment and perhaps contributes to the relapsing nature of schizophrenia. Recent discoveries on the regulatory interactions between micro- and astroglial cells and meningeal immune regulatory T cells (Tregs) cohere with clinical omics data to suggest that: i) activated astrocytes mediate the shift in microglial phenotype via the production of transforming growth factor-beta, which also contributes to the disturbances of dopamine and GABA function in schizophrenia, and ii) systemically impaired functioning of Treg cells contributes to the dysregulation of glial function, the low-grade peripheral inflammation, and the hitherto unexplained predisposition to auto-immunity and reduced lifeexpectancy in schizophrenia, including greater COVID-19 mortality
European-wide policymaking at the urban level: A qualitative study
No full textBackgroundInter-urban area (UA) health inequalities can be as dramatic as those between high and low-income countries. Policies need to focus on the determinants of health specific to UAs to effect change. This study therefore aimed to determine the degree to which policymakers from different countries could make autonomous health and wellbeing policy decisions for their urban jurisdiction area. MethodsWe conducted a cross-sectional, qualitative interview study with policymakers recruited from 8 European countries (N=37). ResultsThe reported autonomy among policymakers varied considerably between countries, from little or no autonomy and strict adherence to national directives (e.g. Slovak Republic) to a high degree of autonomy and ability to interpret national guidelines to local context (e.g. Norway). The main perceived barriers to implementation of local policies were political, and the importance of regular and effective communication with stakeholders, especially politicians, was emphasised. Having qualified health professionals in positions of influence within the UA was cited as a strong driver of the public health agenda at the UA level. ConclusionLocal-level policy development and implementation depends strongly on the degree of autonomy and independence of policymakers, which in turn depends on the organisation, structure and financial budget allocation of public health services. While high levels of centralisation in small, relatively homogenous countries may enhance efficient use of resources, larger, more diverse countries may benefit from devolution to smaller geographical regions. <br/
Modelling Precipitate Amorphization in Zircaloys
No full textThe second phase particles (SPPs) that occur in Zircaloys can undergo amorphization and loss of iron in-reactor, which can have a profound effect on corrosion resistance and irradiation growth. In this paper, a classical model is presented that predicts the interaction between these processes, based on a previously proposed physical mechanism that considers iron release and transport from the SPP as the controlling factor. It is assumed that iron is released into a mobile state by a homogeneous and continuous amorphization and recrystallization process. As iron is released, it diffuses out of the SPP, causing the relative stability of the amorphous phase to increase, until a persistent amorphous layer forms. The model predicts the growth rate of this layer and the rate at which iron is lost from the SPP. It has been used to explore the effect of flux, temperature, and initial SPP iron concentration on the amorphous layer growth and iron loss kinetics. It is predicted that whilst iron loss is correlated with the thickness of the amorphous layer, the relationship is not a simple scaling, and depends on conditions. The model is also able to explain the observed occurrence of an amorphous layer only in an intermediate temperature range as a natural consequence of the competition between the same fundamental mechanisms
A three-dimensional phase-field lattice Boltzmann method for incompressible two-components flows
No full textIn this paper, a lattice Boltzmann model for the coupled Allen-Cahn-Navier-Stokes equations in three dimensions is presented. Two equations are solved: one for the fluid velocity and one for the order parameter. Both are written within the general multiple-relaxation-time framework, where all the equilibrium and forcing terms are described by using the full set of Hermite polynomials. The resultant practical implementation is compact. The gradient of the order parameter can be computed by the non-local finite differences or the local central moments. The latter suffers from grid-scale oscillations. The very good accuracy properties are demonstrated against nine well-consolidated benchmark tests. Specifically, two groups of tests are tackled. In the former, the velocity field is superimposed. Hence, only the equation for the evolution of the order parameter is solved. These numerical experiments demonstrate the ability of the proposed scheme to capture the correct evolution of the interface. In the latter, two immiscible fluids are considered and the two equations are solved. Simulations of the vertical penetration of a wedge-shaped body, two- and three-dimensionalRayleigh-Taylor instability prove that two-fluids systems can be successfully simulated by our approach
Impact of airway Exophiala spp. on children with cystic fibrosis
No full textIntroduction: Isolation of Exophiala species from sputum samples has become increasingly reported in Cystic Fibrosis (CF). However, the clinical significance of Exophiala spp. with regards to the paediatric CF population is unknown. Methods: A case control study was undertaken to compare CF children with and without chronic Exophiala spp. in their sputum samples. Demographic and clinical data were collected retrospectively for each case from the date of Exophiala isolation and for 12 months preceding isolation. Each case was compared to three age and year-matched controls. To determine the effect of Exophiala on clinical course, patients were then followed for 12 months post isolation. Results: In total, 27 of 244 eligible paediatric CF patients (11%) isolated Exophiala spp. on more than one occasion. There were no significant differences in the key clinical parameters: spirometry, mean number of intravenous (IV) antibiotic days and body mass index (BMI), between cases and controls (p=0.91, p=0.56 and p=0.63 respectively). A higher proportion of cases isolated Candida spp. (67% vs 21%, p<0.0001) and Aspergillus fumigatus (37% vs 26%, p=0.37). There was no clinically significant difference in spirometry, mean number of IV antibiotic days and BMI in cases pre and post Exophiala spp. isolation. Posaconazole was the only drug used that successfully eradicated Exophiala. Conclusion: Despite the frequent isolation of Exophiala spp. in this cohort, in most patients it is not associated with significant clinical deterioration. It does however seem to be associated with isolation of other fungi
Investigation of fiber orientation and void content in bagasse fiber composites using image analysis technique
No full textIn this research work, a nondestructive technique of image analysis was explored to determine the fiber orientation and void content in Bagasse fiber reinforced composites. Fiber length, alkali treatment and fiber loading were studied as variables. The fiber orientation was irrespective of the variables of fiber length, fiber loading and alkali treatment. The void content and the size decreased with increases in fiber length and alkali treatment. The alkali treatment resulted in the removal of lignin, making the surface of the fibers rough. It also resulted in making the fiber count fine i.e. reduce the diameter of the fibers and thus presenting more fibers for interaction with resin. Both these phenomena resulted in slower flow of resin. The void content of bagasse fiber composites decreased with higher fiber loading because the higher number of fibers slows the resin flow. However the size i.e. area of the voids increased with the fiber loading from 20 to 30%, probably due to increased wetting difficulty
An Evaluation of Goal Setting in the NHS England Diabetes Prevention Programme
No full textObjective: We know little about how goal setting is actually delivered in routine practice. The National Health Service Diabetes Prevention Programme (NHS-DPP) is a behavioural intervention aiming to prevent progression to Type 2 diabetes in those at risk. It has been delivered across England by four commercial providers. This study aimed to establish whether goal setting in the NHS-DPP was delivered in line with the current evidence base. Design: Observational study and document review. One-hundred-and-eighteen NHS-DPP sessions with 419 people were observed at eight sites (two sites per provider). Main outcome measures: Multiple characteristics of goal setting were reliably coded from each providers’ programme plans (intended goal setting) and from audio-recorded NHS-DPP sessions (actual goal setting). Results: Providers intended to deliver goal setting in 88.3% of sessions, though goal setting was delivered in only 52.5% of sessions. During delivery, the observed goals set across providers were generally specific (62.5%), set privately (53.1%), with goal difficulty rarely mentioned (3.1%). Conclusions: Goal setting in the NHS-DPP is being under-delivered, and not in line with the evidence base for promoting behavioural change. Goal setting in national behaviour change programmes should be optimised and training provided specifically for goal setting
Probing anisotropic mechanical behaviour in Carbamazepine Form III
No full textNanoindentation measurement of the mechanical properties of the (020), (002) and (101) crystal faces in carbamazepine (CBZ) form III revealed that the (020) face had a greater elastic modulus and hardness than the (002) and (101) faces, which had similar modulus and hardness values. Atomic Force Microscopy (AFM) imaging of the indents showed that whilst no surface plastic displacement was observed around the residual indents on the (020) face, indents on both (002) and (101) faces nucleated cracks in multiple orientations and showed slip bands parallel to (020). The computed compliance matrix of CBZ form III was in good agreement with the experimental results and predicted anisotropic stiffness, with E(020) > E(002) > E(101). Modelling also revealed that the molecular flexibility of CBZ results in a less stiff material than that of an equivalent rigid compound. Indentation in one direction results in the opening of the CBZ-butterfly wings whilst in the other two results in their closing. Molecular dynamics simulations confirmed the primary (020) slip plane, consistent with the AFM images of the indents. It was also found that shear on the primary (020) slip plane, requires of the breaking and forming of CBZ hydrogen bonded dimers. The slip plane, (020), was identified as having the lowest structural rugosity and hydrogen bonding density but not the lowest attachment energy
Operational optimization of cyclic gas pipeline network with consideration of thermal hydraulics
No full textFollowing the rapidly increasing global demand for natural gas, many countries are launching projects to expand gas pipeline networks (GPNs). As a result, more cyclic GPNs are under construction with more rigorous physical constraints required, bringing new challenges to GPNs optimization. This paper proposes a novel nonconvex mixed-integer nonlinear programming (MINLP) formulation for operational optimization of the cyclic GPN with simultaneous consideration of thermal hydraulics and flow direction reversibility, which has not been explored in the literature. To solve the proposed MINLP model, a three-level decomposition algorithm is proposed to generate an approximate solution, from which the flow direction is extracted and used to fix all discrete variables in the original MINLP model to construct two-stage NLP models. The NLP models are then solved to improve solution feasibility and quality. The computational results show that the proposed approach outweighs several state-of-the-art commercial MINLP solvers with better solutions and shorter computational time
Impact of weld restraint on the development of distortion and stress during the electron beam welding of a low-alloy steel subject to solid state phase transformation
No full textElectron beam (EB) welding has a low tolerance to inter-part gapping distortion and can generate complicated stresses, which pose challenges to weld quality and integrity. This study investigates welding distortion and stresses in an EB welded plate made from SA508 Grade 4N low-alloy steel. A thermal-metallurgical-mechanical model was developed to predict the temperature, micro-constituents, hardness, distortion and stresses in the EB weldment; the predictions are in good agreement with experimental results. Different restraint conditions on the weld plane were modelled to examine their effects on distortion and stresses. If welding is performed with no restraint, inter-part gapping develops ahead of the beam position that could exceed the tolerance for a sound weld. In contrast, tack welds at the plate ends significantly reduce this gapping, but induce additional tensile stress at the stop-end tack weld. This stress is particularly high as the beam approaches the tack weld. Increasing the extent of the tack welds reduces the tensile stress, while increasing number of distantly distributed narrow tack welds does not help. A full through-length restraint eliminates the opening gap and minimises the development of tensile stresses ahead of the beam that could potentially break the restraint. The applied restraint on the weld plane has little effect on the final residual stress field, since this field mostly develops during cooling after the EB weld is complete. The weld-induced martensitic transformation suppressed tension or promoted compression in the EB weld and heat affected zone (HAZ). A steep gradient of residual stress exists, with high tensile stress concentrated in a narrow region immediately outside the HAZ