Toward a limbic cortical inhibitory network: implications for hypothalamic-pituitary-adrenal responses following chronic stress

A network of interconnected cell groups in the limbic forebrain regulates hypothalamic-pituitary-adrenal (HPA) axis activation during emotionally stressful experiences, and disruption of these systems is broadly implicated in the onset of psychiatric illnesses. A significant challenge has been to unravel the circuitry and mechanisms providing for regulation of HPA output, as these limbic forebrain regions do not provide any direct innervation of HPA effector cell groups in the paraventricular hypothalamus (PVH). Recent evidence will be highlighted that endorses a discrete region within the bed nuclei of the stria terminalis serving as a neural hub for integrating and relaying HPA-inhibitory influences to the PVH during emotional stress, whereas the prevailing view has involved a more complex organization of mulitple cell groups arranged in parallel between the forebrain and PVH. A hypothesis will be advanced that accounts for the capacity of this network to constrain the magnitude and/or duration of HPA axis output in response to emotionally stressful experiences, and for how chronic stress-induced synaptic reorganization in key cell groups may lead to an attrition of these influences, resulting in HPA axis hyperactivity

Assessing the short-term outcomes of a community-based intervention for overweight and obese children: The MEND 5-7 programme

Objective The aim of this study was to report outcomes of the UK service level delivery of MEND (Mind,Exercise,Nutrition...Do it!) 5-7, a multicomponent, community-based, healthy lifestyle intervention designed for overweight and obese children aged 5–7 years and their families. Design Repeated measures. Setting Community venues at 37 locations across the UK. Participants 440 overweight or obese children (42% boys; mean age 6.1 years; body mass index (BMI) z-score 2.86) and their parents/carers participated in the intervention. Intervention MEND 5-7 is a 10-week, family-based, child weight-management intervention consisting of weekly group sessions. It includes positive parenting, active play, nutrition education and behaviour change strategies. The intervention is designed to be scalable and delivered by a range of health and social care professionals. Primary and secondary outcome measures The primary outcome was BMI z-score. Secondary outcome measures included BMI, waist circumference, waist circumference z-score, children's psychological symptoms, parenting self-efficacy, physical activity and sedentary behaviours and the proportion of parents and children eating five or more portions of fruit and vegetables. Results 274 (62%) children were measured preintervention and post-intervention (baseline; 10-weeks). Post-intervention, mean BMI and waist circumference decreased by 0.5 kg/m2 and 0.9 cm, while z-scores decreased by 0.20 and 0.20, respectively (p<0.0001). Improvements were found in children's psychological symptoms (−1.6 units, p<0.0001), parent self-efficacy (p<0.0001), physical activity (+2.9 h/week, p<0.01), sedentary activities (−4.1 h/week, p<0.0001) and the proportion of parents and children eating five or more portions of fruit and vegetables per day (both p<0.0001). Attendance at the 10 sessions was 73% with a 70% retention rate. Conclusions Participation in the MEND 5-7 programme was associated with beneficial changes in physical, behavioural and psychological outcomes for children with complete sets of measurement data, when implemented in UK community settings under service level conditions. Further investigation is warranted to establish if these findings are replicable under controlled conditions

Analysis of Iterative Methods for the Linear Boltzmann Transport Equation

In this article we consider the iterative solution of the linear system of equations arising from the discretisation of the poly-energetic linear Boltzmann transport equation using a discontinuous Galerkin finite element approximation in space, angle, and energy. In particular, we develop preconditioned Richardson iterations which may be understood as generalisations of source iteration in the mono-energetic setting, and derive computable a posteriori bounds for the solver error incurred due to inexact linear algebra, measured in a relevant problem-specific norm. We prove that the convergence of the resulting schemes and a posteriori solver error estimates are independent of the discretisation parameters. We also discuss how the poly-energetic Richardson iteration may be employed as a preconditioner for the generalised minimal residual (GMRES) method. Furthermore, we show that standard implementations of GMRES based on minimising the Euclidean norm of the residual vector can be utilized to yield computable a posteriori solver error estimates at each iteration, through judicious selections of left- and right-preconditioners for the original linear system. The effectiveness of poly-energetic source iteration and preconditioned GMRES, as well as their respective a posteriori solver error estimates, is demonstrated through numerical examples arising in the modelling of photon transport.Comment: 27 pages, 8 figure

Speech Analysis

Contains reports on two research projects

How has big data contributed to obesity research? A review of the literature

There has been growing interest in the potential of ‘big data’ to enhance our understanding in medicine and public health. Although there is no agreed definition of big data, accepted critical components include greater volume, complexity, coverage and speed of availability. Much of these data are ‘found’ (as opposed to ‘made’), in that they have been collected for non-research purposes but could include valuable information for research. The aim of this paper is to review the contribution of ‘found’ data to obesity research to date, and describe the benefits and challenges encountered. A narrative review was conducted to identify and collate peer-reviewed research studies. Database searches conducted up to September 2017 found original studies using a variety of data types and sources. These included: retail sales, transport, geospatial, commercial weight management data, social media, and smartphones and wearable technologies. The narrative review highlights the variety of data uses in the literature: describing the built environment, exploring social networks, estimating nutrient purchases or assessing the impact of interventions. The examples demonstrate four significant ways in which ‘found’ data can complement conventional ‘made’ data: firstly, in moving beyond constraints in scope (coverage, size, and temporality); secondly, in providing objective, quantitative measures; thirdly, in reaching hard-to-access population groups; and lastly in the potential for evaluating real-world interventions. Alongside these opportunities, ‘found’ data come with distinct challenges, such as: ethical and legal questions around access and ownership; commercial sensitivities; costs; lack of control over data acquisition; validity; representativeness; finding appropriate comparators; and complexities of data processing, management and linkage. Despite widespread recognition of the opportunities, the impact of ‘found’ data on academic obesity research has been limited. The merit of such data lies not in their novelty, but in the benefits they could add over and above, or in combination with, conventionally collected data

Systematic review of health-related quality of life and patient-reported outcome measures in Gestational Trophoblastic Disease: A parallel synthesis approach

Gestational Trophoblastic Disease (GTD) is a rare complication of pregnancy that can develop into cancer. Medical outcomes are well researched but evidence is required on the impact of GTD on health-related quality of life (HRQoL) to improve care. The review was conducted to determine the impact of GTD and its treatment on HRQoL and identify how HRQoL is measured and appropriateness of these measures. Quantitative studies found HRQoL in long-term survivors to be at or above population norms. GTD appeared to have a negative impact on HRQoL where patients experience physical, psychological and social sequelae related to the condition. Clinically significant levels of anxiety, depression, sexual dysfunction and fertility-related distress were found. The results should be treated with caution because the evidence base was limited to small heterogeneous samples, retrospective data and the wide range of measures used. Within the qualitative data, new themes emerged including nerve damage, fatigue, amenorrhea, and grief. Currently, these areas are not captured in patient reported outcome measures (PROMs) and the content may not be valid for this population. Further qualitative research could lead to development of a GTD specific PROM providing reliable, meaningful and valid assessments and allowing longitudinal data to be obtained

Efficient High-Order Space-Angle-Energy Polytopic Discontinuous Galerkin Finite Element Methods for Linear Boltzmann Transport

We introduce an $hp$-version discontinuous Galerkin finite element method (DGFEM) for the linear Boltzmann transport problem. A key feature of this new method is that, while offering arbitrary order convergence rates, it may be implemented in an almost identical form to standard multigroup discrete ordinates methods, meaning that solutions can be computed efficiently with high accuracy and in parallel within existing software. This method provides a unified discretisation of the space, angle, and energy domains of the underlying integro-differential equation and naturally incorporates both local mesh and local polynomial degree variation within each of these computational domains. Moreover, general polytopic elements can be handled by the method, enabling efficient discretisations of problems posed on complicated spatial geometries. We study the stability and $hp$-version a priori error analysis of the proposed method, by deriving suitable $hp$-approximation estimates together with a novel inf-sup bound. Numerical experiments highlighting the performance of the method for both polyenergetic and monoenergetic problems are presented.Comment: 27 pages, 2 figure

A systematic review and meta-analysis of community and primary-care-based hepatitis C testing and treatment services that employ direct acting antiviral drug treatments

Background Direct Acting Antiviral (DAAs) drugs have a much lower burden of treatment and monitoring requirements than regimens containing interferon and ribavirin, and a much higher efficacy in treating hepatitis C (HCV). These characteristics mean that initiating treatment and obtaining a virological cure (Sustained Viral response, SVR) on completion of treatment, in non-specialist environments should be feasible. We investigated the English-language literature evaluating community and primary care-based pathways using DAAs to treat HCV infection. Methods Databases (Cinahl; Embase; Medline; PsycINFO; PubMed) were searched for studies of treatment with DAAs in non-specialist settings to achieve SVR. Relevant studies were identified including those containing a comparison between a community and specialist services where available. A narrative synthesis and linked meta-analysis were performed on suitable studies with a strength of evidence assessment (GRADE). Results Seventeen studies fulfilled the inclusion criteria: five from Australia; two from Canada; two from UK and eight from USA. Seven studies demonstrated use of DAAs in primary care environments; four studies evaluated integrated systems linking specialists with primary care providers; three studies evaluated services in locations providing care to people who inject drugs; two studies evaluated delivery in pharmacies; and one evaluated delivery through telemedicine. Sixteen studies recorded treatment uptake. Patient numbers varied from around 60 participants with pathway studies to several thousand in two large database studies. Most studies recruited less than 500 patients. Five studies reported reduced SVR rates from an intention-to-treat analysis perspective because of loss to follow-up before the final confirmatory SVR test. GRADE assessments were made for uptake of HCV treatment (medium); completion of HCV treatment (low) and achievement of SVR at 12 weeks (medium). Conclusion Services sited in community settings are feasible and can deliver increased uptake of treatment. Such clinics are able to demonstrate similar SVR rates to published studies and real-world clinics in secondary care. Stronger study designs are needed to confirm the precision of effect size seen in current studies. Prospero: CRD42017069873