Elevated ACKR2 expression is a common feature of inflammatory arthropathies

Objectives. Chemokines are essential contributors to leucocyte accumulation at sites of inflammatory pathology. Interfering with chemokine or chemokine receptor function therefore represents a plausible therapeutic option. However, our currently limited understanding of chemokine orchestration of inflammatory responses means that such therapies have not yet been fully developed. We have a particular interest in the family of atypical chemokine receptors that fine-tune, or resolve, chemokine-driven responses. In particular we are interested in atypical chemokine receptor 2 (ACKR2), which is a scavenging receptor for inflammatory CC-chemokines and that therefore helps to resolve in vivo inflammatory responses. The objective of the current study was to examine ACKR2 expression in common arthropathies. Methods. ACKR2 expression was measured by a combination of qPCR and immuno-histochemistry. In addition, circulating cytokine and chemokine levels in patient plasma were assessed using multiplexing approaches. Results. Expression of ACKR2 was elevated on peripheral blood cells as well as on leucocytes and stromal cells in synovial tissue. Expression on peripheral blood leucocytes correlated with, and could be regulated by, circulating cytokines with particularly strong associations being seen with IL-6 and hepatocyte growth factor. In addition, expression within the synovium was coincident with aggregates of lymphocytes, potentially atopic follicles and sites of high inflammatory chemokine expression. Similarly increased levels of ACKR2 have been reported in psoriasis and SSc. Conclusion. Our data clearly show increased ACKR2 in a variety of arthropathies and taking into account our, and others’, previous data we now propose that elevated ACKR2 expression is a common feature of inflammatory pathologies

Experiences of those Taking Part in the BeeZee Bodies Family-Based Weight Management Intervention: A Qualitative Evaluation

The need for effective community, child weight management interventions continues. The BeeZee Bodies (BZB) family-based child weight management programme for 7-11-year-olds and 12-15–year-olds has been developed iteratively over five years, with quantitative and qualitative evaluations refining the programmes. The aim of this study was to present the experiences and opinions of those taking part in BZB programmes as part of a real world evaluation. Three focus groups, following a semi-structured protocol, were conducted with 20 participants (15 parents, 5 adolescents) 3 months post-intervention. Analyses were thematic, iterative and underpinned by Grounded Theory. Two themes emerged; (1) programme contents, (2) social interactions, with each sub-divided. Parents described increased appreciation of physical activity and dietary components, improvements in parenting and good relationships with personnel. A wide range of positive personal outcomes and changes within the family were perceived by parents and adolescents including: changes in physical activity take-up, eating habits, portion sizes, and an improved understanding of parenting an overweight child. The parenting skills element further enhanced the social cohesion fostered through attendance. There were opportunities to build new friendships for both parents and adolescents, and for parents to interact with their offspring in a different context, all of which supported behaviour change. The BZB programme was viewed by participants as successful and delivered by engaging personnel. Key strengths were social cohesion generated by including parenting sessions and inclusiveness of the physical activities on offer. BZB has been refined in response to qualitative evaluations and reviews and this process continues

A SQUAMOSA MADS-box gene involved in the regulation of anthocyanin accumulation in bilberry fruits

Anthocyanins are important health promoting phytochemicals that are abundant in many fleshy fruits. Bilberry (Vaccinium myrtillus L.) is one of the best sources of these compounds. Here we report on the expression pattern and functional analysis of a SQUAMOSA (SQUA) class MADS-box transcription factor, VmTDR4, associated with anthocyanin biosynthesis in bilberry. Levels of VmTDR4 expression were spatially and temporally linked with colour development and anthocyanin-related gene expression. Virus induced gene silencing (VIGS) was used to suppress VmTDR4 expression in bilberry resulting in substantial reduction in anthocyanin levels in fully ripe fruits. Chalcone synthase was used a positive control in the VIGS experiments. Additionally, in sectors of fruit tissue in which the expression of the VmTDR4 gene was silenced, the expression of R2R3 MYB family transcription factors related to the biosynthesis of flavonoids were also altered. We conclude that VmTDR4 plays an important role in the accumulation of anthocyanins during normal ripening in bilberry; probably through direct or indirect control of transcription factors belonging to the R2R3 MYB family

Impact of Tide-Topography Interactions on Basal Melting of Larsen C Ice Shelf, Antarctica

Basal melting of ice shelves around Antarctica contributes to formation of Antarctic Bottom Water and can affect global sea level by altering the offshore flow of grounded ice streams and glaciers. Tides influence ice shelf basal melt rate (w(b)) by contributing to ocean mixing and mean circulation as well as thermohaline exchanges with the ice shelf. We use a three-dimensional ocean model, thermodynamically coupled to a nonevolving ice shelf, to investigate the relationship between topography, tides, and w(b) for Larsen C Ice Shelf (LCIS) in the northwestern Weddell Sea, Antarctica. Using our best estimates of ice shelf thickness and seabed topography, we find that the largest modeled LCIS melt rates occur in the northeast, where our model predicts strong diurnal tidal currents (similar to 0.4 m s(-1)). This distribution is significantly different from models with no tidal forcing, which predict largest melt rates along the deep grounding lines. We compare several model runs to explore melt rate sensitivity to geometry, initial ocean potential temperature (theta(0)), thermodynamic parameterizations of heat and freshwater ice-ocean exchange, and tidal forcing. The resulting range of LCIS-averaged w(b) is similar to 0.11-0.44 m a(-1). The spatial distribution of w(b) is very sensitive to model geometry and thermodynamic parameterization while the overall magnitude of w(b) is influenced by theta(0). These sensitivities in w(b) predictions reinforce a need for high-resolution maps of ice draft and sub-ice-shelf seabed topography together with ocean temperature measurements at the ice shelf front to improve representation of ice shelves in coupled climate system models

Strength in diversity: enhancing learning in vocationally-orientated, master's level courses

Postgraduate education in geography, especially at the Master’s level, is undergoing significant changes in the developed world. There is an expansion of vocationally-oriented degree programmes, increasing recruitment of international students, integration of work place skills, and the engagement of non-traditional postgraduate students as departments respond to policies for a more ‘inclusive’ higher education. This paper sets the context by outlining some programmatic changes in selected countries (Australia, the UK, and the USA). We briefly reflect on how postgraduate ‘bars’ or ‘levels’ are defined and explore in detail what ‘diversity’ or ‘heterogeneity’ means in these new postgraduate settings. The paper then explores some examples of practice drawn from our own experiences, whilst recognising that relevance will vary in other contexts. Finally we consider how diversity can be harnessed as a strength that has potential to enhance taught elements of contemporary postgraduate education in and beyond the discipline

Improving response rates using a monetary incentive for patient completion of questionnaires: an observational study

Background: Poor response rates to postal questionnaires can introduce bias and reduce the statistical power of a study. To improve response rates in our trial in primary care we tested the effect of introducing an unconditional direct payment of 5 pound for the completion of postal questionnaires. Methods: We recruited patients in general practice with knee problems from sites across the United Kingdom. An evidence-based strategy was used to follow-up patients at twelve months with postal questionnaires. This included an unconditional direct payment of 5 pound to patients for the completion and return of questionnaires. The first 105 patients did not receive the 5 pound incentive, but the subsequent 442 patients did. We used logistic regression to analyse the effect of introducing a monetary incentive to increase the response to postal questionnaires. Results: The response rate following reminders for the historical controls was 78.1% ( 82 of 105) compared with 88.0% ( 389 of 442) for those patients who received the 5 pound payment (diff = 9.9%, 95% CI 2.3% to 19.1%). Direct payments significantly increased the odds of response ( adjusted odds ratio = 2.2, 95% CI 1.2 to 4.0, P = 0.009) with only 12 of 442 patients declining the payment. The incentive did not save costs to the trial - the extra cost per additional respondent was almost 50 pound. Conclusion: The direct payment of 5 pound significantly increased the completion of postal questionnaires at negligible increase in cost for an adequately powered study

Elevated expression of the chemokine-scavenging receptor D6 is associated with impaired lesion development in psoriasis

D6 is a scavenging-receptor for inflammatory CC chemokines that are essential for resolution of inflammatory responses in mice. Here, we demonstrate that D6 plays a central role in controlling cutaneous inflammation, and that D6 deficiency is associated with development of a psoriasis-like pathology in response to varied inflammatory stimuli in mice. Examination of D6 expression in human psoriatic skin revealed markedly elevated expression in both the epidermis and lymphatic endothelium in "uninvolved" psoriatic skin (ie, skin that was more than 8 cm distant from psoriatic plaques). Notably, this increased D6 expression is associated with elevated inflammatory chemokine expression, but an absence of plaque development, in uninvolved skin. Along with our previous observations of the ability of epidermally expressed transgenic D6 to impair cutaneous inflammatory responses, our data support a role for elevated D6 levels in suppressing inflammatory chemokine action and lesion development in uninvolved psoriatic skin. D6 expression consistently dropped in perilesional and lesional skin, coincident with development of psoriatic plaques. D6 expression in uninvolved skin also was reduced after trauma, indicative of a role for trauma-mediated reduction in D6 expression in triggering lesion development. Importantly, D6 is also elevated in peripheral blood leukocytes in psoriatic patients, indicating that upregulation may be a general protective response to inflammation. Together our data demonstrate a novel role for D6 as a regulator of the transition from uninvolved to lesional skin in psoriasis

Single sensor gait analysis to detect diabetic peripheral neuropathy: A proof of principle study

This study explored the potential utility of gait analysis using a single sensor unit (inertial easurement unit [IMU]) as a simple tool to detect peripheral neuropathy in people with diabetes. Seventeen people (14 men) aged 63±9 years (mean±SD) with diabetic peripheral neuropathy performed a 10-m walk test instrumented with an IMU on the lower back. Compared to a reference healthy control data set (matched by gender, age, and body mass index) both spatiotemporal and gait control variables were different between groups, with walking speed, step time, and SDa (gait control parameter) demonstrating good discriminatory power (receiver operating characteristic area under the curve >0.8). These results provide a proof of principle of this relatively simple approach which, when applied in clinical practice, can detect a signal from those with known diabetes peripheral neuropathy. The technology has the potential to be used both routinely in the clinic and for tele-health applications. Further research should focus on investigating its efficacy as an early indicator of or effectiveness of the management of peripheral neuropathy. This could support the development of interventions to prevent complications such as foot ulceration or Charcot’s foot

The effectiveness and cost-effectiveness of lay counsellor-delivered psychological treatments for harmful and dependent drinking and moderate to severe depression in primary care in India: PREMIUM study protocol for randomized controlled trials.

BACKGROUND: The leading mental health causes of the global burden of disease are depression in women and alcohol use disorders in men. A major hurdle to the implementation of evidence-based psychological treatments in primary care in developing countries is the non-availability of skilled human resources. The aim of these trials is to evaluate the effectiveness and cost-effectiveness of two psychological treatments developed for the treatment of depression and alcohol use disorders in primary care in India. METHODS/DESIGN: This study protocol is for parallel group, randomized controlled trials (Healthy Activity Program for moderate to severe depression, Counselling for Alcohol Problems for harmful and dependent drinking) in eight primary health centres in Goa, India. Adult primary care attendees will be screened with the Patient Health Questionnaire for depression and, in men only, the Alcohol Use Disorders Identification Test for drinking problems. Screen-positive attendees will be invited to participate; men who screen positive for both disorders will be invited to participate in the Counselling for Alcohol Problems trial. Those who consent will be allocated in a 1:1 ratio to receive either the respective psychological treatment plus enhanced usual care or enhanced usual care only using a computer generated allocation sequence, stratified by primary health centre and, for depression, by sex. The enhanced usual care comprises providing primary health centre doctors with contextualized World Health Organization guidelines and screening results. Psychological treatments will be delivered by lay counsellors, over a maximum period of three months. Primary outcomes are severity of disorder and remission rates at three months post-enrolment and, for the Counselling for Alcohol Problems trial, drinking and the impact of drinking on daily lives. Secondary outcomes include severity of disorder and remission rates at 12 months, disability scores, suicidal behaviour and economic impact, and cost-effectiveness at three and 12 months. 500 participants with depression and 400 participants with harmful drinking will be recruited. Primary analyses will be intention-to-treat. DISCUSSION: These trials may offer a new approach for the treatment of moderate-severe depression and drinking problems in primary care that is potentially scalable as it relies on delivery by a single pool of lay counsellors. TRIAL REGISTRATION: Both trials are registered with the International Society for the Registration of Clinical Trials (Healthy Activity Programme registration number ISRCTN95149997; Counselling for Alcohol Problems registration number ISRCTN76465238)