Shared genetic contribution of type 2 diabetes and cardiovascular disease: Implications for prognosis and treatment

Purpose of Review: The increased cardiovascular disease (CVD) risk in subjects with type 2 diabetes (T2D) is well established. This review collates the available evidence and assesses the shared genetic background between T2D and CVD: the causal contribution of common risk factors to T2D and CVD and how genetics can be used to improve drug development and clinical outcomes. Recent Findings: Large-scale genome-wide association studies (GWAS) of T2D and CVD support a shared genetic background but minimal individual locus overlap. Summary: Mendelian randomisation (MR) analyses show that T2D is causal for CVD, but GWAS of CVD, T2D and their common risk factors provided limited evidence for individual locus overlap. Distinct but functionally related pathways were enriched for CVD and T2D genetic associations reflecting the lack of locus overlap and providing some explanation for the variable associations of common risk factors with CVD and T2D from MR analyses

Age-related variation in non-breeding foraging behaviour and carry-over effects on fitness in an extremely long-lived bird

Senescence has been widely documented in wild vertebrate populations, yet the proximate drivers of age‐related declines in breeding success, including allocation trade‐offs and links with foraging performance, are poorly understood. For long‐lived, migratory species, the non‐breeding period represents a critical time for investment in self‐maintenance and restoration of body condition, which in many species is linked to fitness. However, the relationships between age, non‐breeding foraging behaviour and fitness remain largely unexplored. We performed a cross‐sectional study, investigating age‐related variation in the foraging activity, distribution and diet of an extremely long‐lived seabird, the wandering albatross Diomedea exulans, during the non‐breeding period. Eighty‐two adults aged 8–33 years were tracked with geolocator‐immersion loggers, and body feathers were sampled for stable isotope analysis. We tested for variation in metrics of foraging behaviour and linked age‐related trends to subsequent reproductive performance. There was an age‐related decline in the number of landings (a proxy of foraging effort) during daylight hours, and a decrease in body feather δ¹³C values in older males but not females, yet this did not accompany an age‐related shift in distributions. Males conducted fewer landings than females, and the sexes showed some spatial segregation, with males foraging further south, likely due to their differential utilization of winds. Although younger (<20 years) birds had higher foraging effort, they all went on to breed successfully the following season. In contrast, among older (20+ years) birds, individuals that landed more often were more likely to defer breeding or fail during incubation, suggesting they have lower foraging success. As far as we are aware, this is the first demonstration of an age‐specific carry‐over effect of foraging behaviour in the non‐breeding period on subsequent reproductive performance. This link between foraging behaviour and fitness in late but not early adulthood indicates that the ability of individuals to forage efficiently outside the breeding period may be an important driver of fitness differences in old age. A plain language summary is available for this article

Consumer credit in comparative perspective

We review the literature in sociology and related fields on the fast global growth of consumer credit and debt and the possible explanations for this expansion. We describe the ways people interact with the strongly segmented consumer credit system around the world—more specifically, the way they access credit and the way they are held accountable for their debt. We then report on research on two areas in which consumer credit is consequential: its effects on social relations and on physical and mental health. Throughout the article, we point out national variations and discuss explanations for these differences. We conclude with a brief discussion of the future tasks and challenges of comparative research on consumer credit.Accepted manuscrip

Direct radiative effect of aerosols emitted by transport from road, shipping and aviation

Aerosols and their precursors are emitted abundantly by transport activities. Transportation constitutes one of the fastest growing activities and its growth is predicted to increase significantly in the future. Previous studies have estimated the aerosol direct radiative forcing from one transport sub-sector, but only one study to our knowledge estimated the range of radiative forcing from the main aerosol components (sulphate, black carbon (BC) and organic carbon) for the whole transportation sector. In this study, we compare results from two different chemical transport models and three radiation codes under different hypothesis of mixing: internal and external mixing using emission inventories for the year 2000. The main results from this study consist of a positive direct radiative forcing for aerosols emitted by road traffic of +20±11 mW m−2 for an externally mixed aerosol, and of +32±13 mW m−2 when BC is internally mixed. These direct radiative forcings are much higher than the previously published estimate of +3±11 mW m−2. For transport activities from shipping, the net direct aerosol radiative forcing is negative. This forcing is dominated by the contribution of the sulphate. For both an external and an internal mixture, the radiative forcing from shipping is estimated at −26±4 mW m−2. These estimates are in very good agreement with the range of a previously published one (from −46 to −13 mW m−2) but with a much narrower range. By contrast, the direct aerosol forcing from aviation is estimated to be small, and in the range −0.9 to +0.3 mW m−2

Neuroprotective actions of leptin facilitated through balancing mitochondrial morphology and improving mitochondrial function

Authors would like to acknowledge ARUK for supporting this research. YC is Chinese Scholarship recipient. The University of St Andrews is a charity registered in Scotland: No SC013532Mitochondrial dysfunction has a recognised role in the progression of Alzheimer's disease (AD) pathophysiology. Cerebral perfusion becomes increasingly inefficient throughout ageing, leading to unbalanced mitochondrial dynamics. This effect is exaggerated by amyloid β (Aβ) and phosphorylated tau, two hallmark proteins of AD pathology. A neuroprotective role for the adipose‐derived hormone, leptin, has been demonstrated in neuronal cells. However, its effects with relation to mitochondrial function in AD remain largely unknown. To address this question, we have used both a glucose‐serum deprived (CGSD) model of ischaemic stroke in SH‐SY5Y cells and a Aβ1‐42‐treatment model of AD in differentiated hippocampal cells. Using a combination of JC‐1 and MitoRed staining techniques, we show that leptin prevents depolarisation of the mitochondrial membrane and excessive mitochondrial fragmentation induced by both CGSD and Aβ1‐42. Thereafter, we used ELISAs and a number of activity assays to reveal the biochemical underpinnings of these processes. Specifically, leptin was seen to inhibit upregulation of the mitochondrial fission protein Fis1 and downregulation of the mitochondrial fusion protein, Mfn2. Furthermore, leptin was seen to upregulate the expression and activity of the antioxidant enzyme, monoamine oxidase B. Herein we provide the first demonstration that leptin is sufficient to protect against aberrant mitochondrial dynamics and resulting loss of function induced by both CGSD and Aβ1‐42. We conclude that the established neuroprotective actions of leptin may be facilitated through regulation of mitochondrial dynamics.Publisher PDFPeer reviewe

Intervention fidelity in a school-based diet and physical activity intervention in the UK:Active for Life Year 5

Active for Life Year 5 (AFLY5) is an educational programme for Year 5 children (aged 9-10) designed to increase children's physical activity, decrease sedentary behaviour and increase fruit and vegetable intake. This paper reports findings from a process evaluation embedded within a randomised controlled trial evaluating the programme's effectiveness. It considers the fidelity of implementation of AFLY5 with a focus on three research questions: 1. To what extent was the intervention delivered as planned? 2. In what ways, if any, did the teachers amend the programme? and 3. What were the reasons for any amendments?Mixed methods were used including data collection via observation of the intervention delivery, questionnaire, teacher's intervention delivery log and semi-structured interviews with teachers and parents. Qualitative data were analysed thematically and quantitative data were summarised using descriptive statistics.Following training, 42 of the 43 intervention school teachers/teaching staff (98%) were confident they could deliver the nutrition and physical activity lessons according to plan. The mean number of lessons taught was 12.3 (s.d. 3.7), equating to 77% of the intervention. Reach was high with 95% of children in intervention schools receiving lessons. A mean of 6.2 (s.d. 2.6) out of 10 homeworks were delivered. Median lesson preparation time was 10 min (IQR 10-20) and 28% of lessons were reported as having been amended. Qualitative findings revealed that those who amended the lessons did so to differentiate for student ability, update them for use with new technologies and to enhance teacher and student engagement. Teachers endorsed the aims of the intervention, but some were frustrated with having to adapt the lesson materials. Teachers also a reported tendency to delegate the physical activity lessons to other staff not trained in the intervention.Fidelity of intervention implementation was good but teachers' enthusiasm for the AFLY5 programme was mixed despite them believing that the messages behind the lessons were important. This may have meant that the intervention messages were not delivered as anticipated and explain why the intervention was found not to be effective.ISRCTN50133740.Rona Campbell, Emma Rawlins, Sian Wells, Ruth R. Kipping, Catherine R. Chittleborough, Tim J. Peters, Debbie A. Lawlor and Russell Jag

Considerations for Individual-Level Versus Whole-School Physical Activity Interventions:Stakeholder Perspectives

Strategies to address declining physical activity levels among children and adolescents have focused on ‘individual-level’ approaches which often fail to demonstrate impact. Recent attention has been on an alternative ‘whole-school’ approach to increasing physical activity that involves promoting physical activity throughout all aspects of the school environment. There is, however, a lack of evidence on how whole-school physical activity approaches could be implemented in the UK. This qualitative study explored perspectives of key stakeholders on potential reasons for the lack of impact of individual-level school-based interventions on children’s physical activity, and key considerations for adopting a whole-school approach. Nineteen semi-structured interviews were conducted with a range of stakeholders involved in the implementation of physical activity programmes in UK schools. Data were analysed using an inductive approach. Respondents suggested that individual-level school-based interventions to increase physical activity often failed to consult end users in the design and were typically implemented in environments unsupportive of long-term change. They subsequently outlined specific barriers and key facilitators for the adoption and implementation of whole-school approaches in UK settings and recommended a shift in research foci towards building an evidence base around educational outcomes and whole-school implementation insights

Recognising the importance of 'family time-out' in consultations: An exploratory qualitative study

Objectives: Patients are often accompanied by family or companions during consultations, but little is known about how this might influence the process. We explored how the presence of a companion in a consultation contributes to communication and the decision-making process. Design: Observational study. Setting: A teaching hospital and a district general hospital in south-west England. Participants: 31 patients and their physicians were observed during consultations in which decisions to undergo palliative chemotherapy were made. Each patient was accompanied by at least one companion. Outcome measures: Communication patterns between physicians, patients and companions. Results: In addition to standard patient/physician interactions, patients and companions were often found to discuss medical information and exchange opinions between themselves without the physician actively participating. We called these instances 'family timeout'. On the occasion of disagreement between patients and companions about preferred treatment options, physicians and patients were able to agree the decision while acknowledging the differences in opinion. Conclusions: Instances of 'family time-out' may contribute to better consultation outcomes because they are understood and supported by the patient's social system. This study highlights the potentially important role of exchanges between patients and companions during consultations and how physicians may benefit from observation of such exchanges. We recommend testing the value of making space for family time-out during consultations. Also, we recommend further study into the medical ethics of family time-out. While the focus here is on palliative chemotherapy, this finding has implications for other consultations, particularly those involving difficult treatment decisions

Effectiveness and cost-effectiveness of the PLAN-A intervention, a peer led physical activity program for adolescent girls:Results of a cluster randomised controlled trial

Background Physical activity is associated with improved health. Girls are less active than boys. Pilot work showed that a peer-led physical activity intervention called PLAN-A was a promising method of increasing physical activity in secondary school age girls. This study examined the effectiveness and cost-effectiveness of the PLAN-A intervention. Methods We conducted a cluster randomised controlled trial with Year 9 (13–14 year old) girls recruited from 20 secondary schools. Schools were randomly assigned to the PLAN-A intervention or a non-intervention control group after baseline data collection. Girls nominated students to be peer leaders. The top 18 % of girls nominated by their peers in intervention schools received three days of training designed to prepare them to support physical activity. Data were collected at two time points, baseline (T0) and 5–6 months post-intervention (T1). Participants wore an accelerometer for seven days to assess the primary outcome of mean weekday minutes of moderate-to-vigorous physical activity (MVPA). Multivariable mixed effects linear regression was used to estimate differences in the primary outcome between the two arms on an Intention-to-Treat (ITT) basis. Resource use and quality of life were measured and a within trial economic evaluation from a public sector perspective was conducted. Results A total of 1558 girls were recruited to the study. At T0, girls in both arms engaged in an average of 51 min of MVPA per weekday. The adjusted mean difference in weekday MVPA at T1 was − 2.84 min per day (95 % CI = -5.94 to 0.25) indicating a slightly larger decline in weekday MVPA in the intervention group. Results were broadly consistent when repeated using a multiple imputation approach and for pre-specified secondary outcomes and sub-groups. The mean cost of the PLAN-A intervention was £2817 per school, equivalent to £31 per girl. Economic analyses indicated that PLAN-A did not lead to demonstrable cost-effectiveness in terms of cost per unit change in QALY. Conclusions This study has shown that the PLAN-A intervention did not result in higher levels of weekday MVPA or associated secondary outcomes among Year 9 girls. The PLAN-A intervention should not be disseminated as a public health strategy