Study of Determined Town and Village Green Applications: Final Report to Common Land Team, Defra

The purpose of the research, as set out in the Project Brief, was to ‘examine a sample of the sites which have been registered as town or village greens (TVGs) since January 2004 as well as a sample of those that have not been registered’. The common term for both successful and unsuccessful applications is that either outcome has been ‘determined’ by Commons Registration Authority (CRA), therefore the study was an investigation into determined town and village green (dTVG) applications. The project also set out to examine whether the sites were earmarked for development in local development plans or subject to planning applications. The full diversity of sites, both approved and rejected, was analysed

Mental health resilience in the adolescent offspring of parents with depression:a prospective longitudinal study

Background Young people whose parents have depression have a greatly increased risk of developing a psychiatric disorder, but poor outcomes are not inevitable. Identification of the contributors to mental health resilience in young people at high familial risk is an internationally recognised priority. Our objectives were to identify protective factors that predict sustained good mental health in adolescents with a parent with depression and to test whether these contribute beyond what is explained by parent illness severity. Methods The Early Prediction of Adolescent Depression study (EPAD) is a prospective longitudinal study of offspring of parents with recurrent depression. Parents with recurrent major depressive disorder, co-parents, and offspring (aged 9–17 years at baseline) were assessed three times over 4 years in a community setting. Offspring outcomes were operationalised as absence of mental health disorder, subthreshold symptoms, or suicidality on all three study occasions (sustained good mental health); and better than expected mental health (mood and behavioural symptoms at follow-up lower than predicted given severity of parental depression). Family, social, cognitive, and health behaviour predictor variables were assessed using interview and questionnaire measures. Findings Between February and June, 2007, we screened 337 families at baseline, of which 331 were eligible. Of these, 262 completed the three assessments and were included in the data for sustained mental health. Adolescent mental health problems were common, but 53 (20%) of the 262 adolescents showed sustained good mental health. Index parent positive expressed emotion (odds ratio 1·91 [95% CI 1·31–2·79]; p=0·001), co-parent support (1·90 [1·38–2·62]; p<0·0001), good-quality social relationships (2·07 [1·35–3·18]; p=0·001), self-efficacy (1·49 [1·05–2·11]; p=0·03), and frequent exercise (2·96 [1·26–6·92]; p=0·01) were associated with sustained good mental health. Analyses accounting for parent depression severity were consistent, but frequent exercise only predicted better than expected mood-related mental health (β=–0·22; p=0·0004) not behavioural mental health, whereas index parents' expression of positive emotions predicted better than expected behavioural mental health (β=–0·16; p=0·01) not mood-related mental health. Multiple protective factors were required for offspring to be free of mental health problems (zero or one protective factor, 4% sustained good mental health; two protective factors, 10%; three protective factors, 13%, four protective factors, 38%; five protective factors, 48%). Interpretation Adolescent mental health problems are common, but not inevitable, even when parental depression is severe and recurrent. These findings suggest that prevention programmes will need to enhance multiple protective factors across different domains of functioning

The health informatics cohort enhancement project (HICE): using routinely collected primary care data to identify people with a lifetime diagnosis of psychotic disorder

Background: We have previously demonstrated that routinely collected primary care data can be used to identify potential participants for trials in depression [1]. Here we demonstrate how patients with psychotic disorders can be identified from primary care records for potential inclusion in a cohort study. We discuss the strengths and limitations of this approach; assess its potential value and report challenges encountered. Methods: We designed an algorithm with which we searched for patients with a lifetime diagnosis of psychotic disorders within the Secure Anonymised Information Linkage (SAIL) database of routinely collected health data. The algorithm was validated against the "gold standard" of a well established operational criteria checklist for psychotic and affective illness (OPCRIT). Case notes of 100 patients from a community mental health team (CMHT) in Swansea were studied of whom 80 had matched GP records. Results: The algorithm had favourable test characteristics, with a very good ability to detect patients with psychotic disorders (sensitivity > 0.7) and an excellent ability not to falsely identify patients with psychotic disorders (specificity > 0.9). Conclusions: With certain limitations our algorithm can be used to search the general practice data and reliably identify patients with psychotic disorders. This may be useful in identifying candidates for potential inclusion in cohort studies

E-cadherin can limit the transforming properties of activating β-catenin mutations

Wnt pathway deregulation is a common characteristic of many cancers. But only Colorectal Cancer predominantly harbours mutations in APC, whereas other cancer types (hepatocellular carcinoma, solid pseudopapillary tumours of pancreas) have activating mutations in β-catenin (CTNNB1). We have compared the dynamics and the potency of β-catenin mutations in vivo. Within the murine small intestine (SI), an activating mutation of β-catenin took much longer to achieve a Wnt deregulation and acquire a crypt-progenitor-cell (CPC) phenotype than Apc or Gsk3 loss. Within the colon, a single activating mutation of β-catenin was unable to drive Wnt deregulation or induce the CPC phenotype. This ability of β-catenin mutation to differentially transform the SI versus the colon correlated with significantly higher expression of the β-catenin binding partner E-cadherin. This increased expression is associated with a higher number of E-cadherin:β-catenin complexes at the membrane. Reduction of E-cadherin synergised with an activating mutation of β-catenin so there was now a rapid CPC phenotype within the colon and SI. Thus there is a threshold of β-catenin that is required to drive transformation and E-cadherin can act as a buffer to prevent β-catenin accumulation

Multicentre, randomised clinical trial of paediatric concussion assessment of rest and exertion (PedCARE): a study to determine when to resume physical activities following concussion in children.

INTRODUCTION: Rest until symptom-free, followed by a progressive stepwise return to activities, is often prescribed in the management of paediatric concussions. Recent evidence suggests prolonged rest may hinder recovery, and early resumption of physical activity may be associated with more rapid recovery postconcussion. The primary objective is to determine whether the early reintroduction of non-contact physical activity beginning 72 hours postinjury reduces postconcussive symptoms at 2 weeks in children following an acute concussion as compared with a rest until asymptomatic protocol. METHODS AND ANALYSIS: This study is a randomised clinical trial across three Canadian academic paediatric emergency departments. A total of 350 participants, aged 10-17.99 years, who present within 48 hours of an acute concussion, will be recruited and randomly assigned to either the study intervention protocol (resumption of physical activity 72 hours postconcussion even if experiencing symptoms) or physical rest until fully asymptomatic. Participants will document their daily physical and cognitive activities. Follow-up questionnaires will be completed at 1, 2 and 4 weeks postinjury. Compliance with the intervention will be measured using an accelerometer (24 hours/day for 14 days). Symptoms will be measured using the validated Health and Behaviour Inventory. A linear multivariable model, adjusting for site and prognostically important covariates, will be tested to determine differences between groups. The proposed protocol adheres to the RCT-CONSORT guidelines. DISCUSSION: This trial will determine if early resumption of non-contact physical activity following concussion reduces the burden of concussion and will provide healthcare professionals with the evidence by which to recommend the best timing of reintroducing physical activities

The Effect of Body Size on Countermovement Jump Kinetics in Children aged 7 to 11 years

The purpose this study was to examine the effect of body size oncountermovement jump (CMJ)kinetics in children.Participants(n = 160) aged 7-11 years, divided equally by sex and into primary school year groups(years 3, 4, 5 and 6), each performedone CMJ on aforce platform. The variables bodyweight(BW), peak force (Fmax), in-jump minimum force (IMF), in-jump vertical force range (IFR) and basic rate of force development (BRFD)wereattained from the force-time history and then subsequently scaled to account for body size. A significant age, sex and interaction effect werefound for theabsolutevariables BW, IMF, Fmaxand IFR (P 0.05). No significant age or sex differences were observed for normalised or allometrically scaled values(P > 0.05). The results indicate thatgirls and boys can be grouped together but that body size must be accounted for to enable accurate conclusions to be drawn independent of growth.Bodysizesignificantlyeffects the representation of CMJ kinetic results and therefore, future studies should report both absolute and scaled values.Future research should developan age-appropriate criterion method for children in order to determine processed CMJ variables to further investigate neuromuscular performance of children

Using Real-World Data to Guide Ustekinumab Dosing Strategies for Psoriasis: A Prospective Pharmacokinetic-Pharmacodynamic Study.

Variation in response to biologic therapy for inflammatory diseases, such as psoriasis, is partly driven by variation in drug exposure. Real-world psoriasis data were used to develop a pharmacokinetic/pharmacodynamic (PK/PD) model for the first-line therapeutic antibody ustekinumab. The impact of differing dosing strategies on response was explored. Data were collected from a UK prospective multicenter observational cohort (491 patients on ustekinumab monotherapy, drug levels, and anti-drug antibody measurements on 797 serum samples, 1,590 measurements of Psoriasis Area Severity Index (PASI)). Ustekinumab PKs were described with a linear one-compartment model. A maximum effect (Emax ) model inhibited progression of psoriatic skin lesions in the turnover PD mechanism describing PASI evolution while on treatment. A mixture model on half-maximal effective concentration identified a potential nonresponder group, with simulations suggesting that, in future, the model could be incorporated into a Bayesian therapeutic drug monitoring "dashboard" to individualize dosing and improve treatment outcomes

Persistence and Effectiveness of Non-Biologic Systemic Therapies for Moderate-Severe Psoriasis in Adults: a Systematic Review

BACKGROUND: The persistence and effectiveness of systemic therapies for moderate-to-severe psoriasis in current clinical practice are poorly characterized. OBJECTIVES: To systematically review observational studies investigating the persistence and effectiveness of acitretin, ciclosporin, fumaric acid esters (FAE) and methotrexate, involving at least 100 adult patients with moderate-to-severe psoriasis, exposed to therapy for ≥ 3 months. METHODS: MEDLINE, Embase, the Cochrane Library and PubMed were searched from 1 January 2007 to 1 November 2017 for observational studies reporting on persistence (therapy duration or the proportion of patients discontinuing therapy during follow-up) or effectiveness [improvements in Psoriasis Area and Severity Index (PASI) or Physician's Global Assessment (PGA)]. This review was registered with PROSPERO, number CRD42018099771. RESULTS: Of 411 identified studies, eight involving 4624 patients with psoriasis were included. Variations in the definitions and analyses of persistence and effectiveness outcomes prevented a meta-analysis from being conducted. One prospective multicentre study reported drug survival probabilities of 23% (ciclosporin), 42% (acitretin) and 50% (methotrexate) at 1 year. Effectiveness outcomes were not reported for either acitretin or ciclosporin. The persistence and effectiveness of FAE and methotrexate were better characterized, but mean discontinuation times ranged from 28 to 50 months for FAE and 7·7 to 22·3 months for methotrexate. At 12 months of follow-up, three studies reported that 76% (FAE), 53% (methotrexate) and 59% (methotrexate) of patients achieved ≥ 75% reduction in PASI, and one reported that 76% of FAE-exposed patients achieved a markedly improved or clear PGA. CONCLUSIONS: The comparative persistence and effectiveness of acitretin, ciclosporin, FAE and methotrexate in real-world clinical practice in the past decade cannot be well described due to the inconsistency of the methods used