Role of microRNAs in the age-associated decline of pancreatic beta cell function in rat islets

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.AIMS/HYPOTHESIS: Ageing can lead to reduced insulin sensitivity and loss of pancreatic beta cell function, predisposing individuals to the development of diabetes. The aim of this study was to assess the contribution of microRNAs (miRNAs) to age-associated beta cell dysfunction. METHODS: The global mRNA and miRNA profiles of 3- and 12-month-old rat islets were collected by microarray. The functional impact of age-associated differences in miRNA expression was investigated by mimicking the observed changes in primary beta cells from young animals. RESULTS: Beta cells from 12-month-old rats retained normal insulin content and secretion, but failed to proliferate in response to mitotic stimuli. The islets of these animals displayed modifications at the level of several miRNAs, including upregulation of miR-34a, miR-124a and miR-383, and downregulation of miR-130b and miR-181a. Computational analysis of the transcriptomic modifications observed in the islets of 12-month-old rats revealed that the differentially expressed genes were enriched for miR-34a and miR-181a targets. Indeed, the induction of miR-34a and reduction of miR-181a in the islets of young animals mimicked the impaired beta cell proliferation observed in old animals. mRNA coding for alpha-type platelet-derived growth factor receptor, which is critical for compensatory beta cell mass expansion, is directly inhibited by miR34a and is likely to be at least partly responsible for the effects of this miRNA. CONCLUSIONS/INTERPRETATION: Changes in the level of specific miRNAs that occur during ageing affect the proliferative capacity of beta cells. This might reduce their ability to expand under conditions of increased insulin demand, favouring the development of type 2 diabetes.Swiss National Science FoundationFondation Francophone pour la Recherche sur le DiabèteWellcome Trust Senior Investigator AwardMRC Programme GrantRoyal Society Wolfson Research Merit AwardWellcome Trust project gran

Standard evaluation framework for weight management interventions

This document builds on the ‘Standard Evaluation Framework (SEF) for weight management interventions’, published by NOO in April 2009.1 It takes the principles described in the original SEF and applies them to dietary interventions. It contains a list of ‘essential’ and ‘desirable’ criteria for data required for a comprehensive and robust evaluation. Essential criteria are the minimum data and information recommended to perform a basic evaluation of an intervention that sets out to improve diet. Desirable criteria are additional data that would improve the quality of an evaluation, and enhance understanding about what has been achieved, and the processes that have taken place during the intervention. A glossary of terms is available on page 35

On Resilient Behaviors in Computational Systems and Environments

The present article introduces a reference framework for discussing resilience of computational systems. Rather than a property that may or may not be exhibited by a system, resilience is interpreted here as the emerging result of a dynamic process. Said process represents the dynamic interplay between the behaviors exercised by a system and those of the environment it is set to operate in. As a result of this interpretation, coherent definitions of several aspects of resilience can be derived and proposed, including elasticity, change tolerance, and antifragility. Definitions are also provided for measures of the risk of unresilience as well as for the optimal match of a given resilient design with respect to the current environmental conditions. Finally, a resilience strategy based on our model is exemplified through a simple scenario.Comment: The final publication is available at Springer via http://dx.doi.org/10.1007/s40860-015-0002-6 The paper considerably extends the results of two conference papers that are available at http://ow.ly/KWfkj and http://ow.ly/KWfgO. Text and formalism in those papers has been used or adapted in the herewith submitted pape

Long-term glycemic variability and risk of adverse outcomes: a systematic review and meta-analysis

OBJECTIVE: Glycemic variability is emerging as a measure of glycemic control, which may be a reliable predictor of complications. This systematic review and meta-analysis evaluates the association between HbA1c variability and micro- and macrovascular complications and mortality in type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: Medline and Embase were searched (2004–2015) for studies describing associations between HbA1c variability and adverse outcomes in patients with type 1 and type 2 diabetes. Data extraction was performed independently by two reviewers. Random-effects meta-analysis was performed with stratification according to the measure of HbA1c variability, method of analysis, and diabetes type. RESULTS: Seven studies evaluated HbA1c variability among patients with type 1 diabetes and showed an association of HbA1c variability with renal disease (risk ratio 1.56 [95% CI 1.08–2.25], two studies), cardiovascular events (1.98 [1.39–2.82]), and retinopathy (2.11 [1.54–2.89]). Thirteen studies evaluated HbA1c variability among patients with type 2 diabetes. Higher HbA1c variability was associated with higher risk of renal disease (1.34 [1.15–1.57], two studies), macrovascular events (1.21 [1.06–1.38]), ulceration/gangrene (1.50 [1.06–2.12]), cardiovascular disease (1.27 [1.15–1.40]), and mortality (1.34 [1.18–1.53]). Most studies were retrospective with lack of adjustment for potential confounders, and inconsistency existed in the definition of HbA1c variability. CONCLUSIONS: HbA1c variability was positively associated with micro- and macrovascular complications and mortality independently of the HbA1c level and might play a future role in clinical risk assessment

Assessment of the benefits of user involvement in health research from the Warwick Diabetes Care Research User Group : a qualitative case study

Objective  To assess the benefits of involving health-care users in diabetes research. Design and participants  For this qualitative case study, semi-structured interviews were conducted with researchers who had worked extensively with the group. During regular meetings of the Research User Group, members discussed their views of the group's effectiveness as part of the meeting's agenda. Interviews and discussions were transcribed, coded using N-Vivo software and analysed using constant comparative methods. Results  Involvement of users in research was generally seen as contributing to effective and meaningful research. However, the group should not be considered to be representative of the patient population or participants of future trials. An important contributor to the group's success was its longstanding nature, enabling users to gain more insight into research and form constructive working relationships with researchers. The user-led nature of the group asserted itself, especially, in the language used during group meetings. A partial shift of power from researchers to users was generally acknowledged. Users' main contribution was their practical expertise in living with diabetes, but their involvement also helped researchers to remain connected to the `real world' in which research would be applied. While the group's work fulfilled established principles of consumer involvement in research, important contributions relying on personal interaction between users and researchers were hard to evaluate by process measures alone. Conclusions  We demonstrated the feasibility, acceptability and effectiveness of this longstanding, experienced, lay-led research advisory group. Its impact on research stems from the continuing interaction between researchers and users, and the general ethos of learning from each other in an on-going process. Both process measures and qualitative interviews with stakeholders are needed to evaluate the contributions of service users to health research

Pathways to economic well-being among teenage mothers in Great Britain

The present study examines pathways to independence from social welfare among 738 teenage mothers, participants of the 1970 British Cohort Study, who were followed up at age 30 years. Using a longitudinal design, a pathway model is tested, examining linkages between family social background, cognitive ability, school motivation, and individual investments in education, as well as work- and family-related roles. The most important factors associated with financial independence by age 30 are continued attachment to the labor market as well as a stable relationship with a partner (not necessarily the father of the child). Pathways to financial independence, in turn, are predicted through own cognitive resources, school motivation, and family cohesion. Implications of findings for policy making are discussed.© 2010 Hogrefe Publishing

On narrowing coated conductor film: emergence of granularity-induced field hysteresis of transport critical current

Critical current density Jc in polycrystalline or granular superconducting material is known to be hysteretic with applied field H due to the focusing of field within the boundary between adjacent grains. This is of concern in the so-called coated conductors wherein superconducting film is grown on a granular, but textured surface of a metal substrate. While previous work has mainly been on Jc determined using induced or magnetization currents, the present work utilizes transport current via an applied potential in strip geometry. It is observed that the effect is not as pronounced using transport current, probably due to a large difference in criterion voltage between the two types of measurements. However, when the films are narrowed by patterning into 200-, 100-, or 80-micron, the hysteresis is clearly seen, because of the forcing of percolation across higher-angle grain boundaries. This effect is compared for films grown on ion-beam-assisted-deposited (IBAD) YSZ substrate and those grown on rolling-assisted-biaxially-textures substrates (RABiTS) which have grains that are about ten times larger. The hysteresis is more pronounced for the latter, which is more likely to have a weak grain boundary spanning the width of the microbridge. This is also of concern to applications in which coated conductors will be striated in order to reduce of AC losses.Comment: text-only: 10 pages, plus 5 figures on 5 page

Political brands: can parties be distinguished by their online brand personality?

This paper investigates whether or not five English political parties are differentiating themselves based on the brand personality they are communicating through their websites. The relative brand positions of five English political parties are analysed using Aaker’s brand personality scale. The text from each party website is analysed using content analysis and a dictionary-based tool. The results are plotted in relation to one another on a correspondence analysis map. We find that the two main dimensions on which parties' brand personalities differ relate to the trade-offs between communicating Competence and communicating Sincerity, and between communicating Sophistication and communicating Ruggedness. We find that parties' brand personalities are distinctive, with the exception of the Green party, and that the position of one party, the United Kingdom Independence Party, is particularly distinctive. Our research uses Aaker’s existing framework for thinking about brand personalities, rather than creating a new framework for politics. By using an existing framework, we are able to use tools developed in other disciplines, and show their usefulness for the study of political marketing

Pharmacists in Pharmacovigilance: Can Increased Diagnostic Opportunity in Community Settings Translate to Better Vigilance?

The pharmacy profession has undergone substantial change over the last two to three decades. Whilst medicine supply still remains a central function, pharmacist’s roles and responsibilities have become more clinic and patient focused. In the community (primary care), pharmacists have become important providers of healthcare as Western healthcare policy advocates patient self-care. This has resulted in pharmacists taking on greater responsibility in managing minor illness and the delivery of public health interventions. These roles require pharmacists to more fully use their clinical skills, and often involve diagnosis and therapeutic management. Community pharmacists are now, more than ever before, in a position to identify, record and report medication safety incidents. However, current research suggests that diagnostic ability of community pharmacists is questionable and they infrequently report to local or national schemes. The aim of this paper is to highlight current practice and suggest ways in which community pharmacy can more fully contribute to patient safety

Adolescent self-control predicts midlife hallucinatory experiences:40-year follow-up of a national birth cohort

Associations between self-control in adolescence and adult mental health are unclear in the general population; to our knowledge, no study has investigated self-control in relation to psychotic-like symptoms