Does the risk of childhood diabetes mellitus require revision of the guideline values for nitrate in drinking water?

In recent years, several studies have addressed a possible relationship between nitrate exposure and childhood type 1 insulin-dependent diabetes mellitus. The present ecologic study describes a possible relation between the incidence of type 1 diabetes and nitrate levels in drinking water in The Netherlands, and evaluates whether the World Health Organization and the European Commission standard for nitrate in drinking water (50 mg/L) is adequate to prevent risk of this disease. During 1993-1995 in The Netherlands, 1,104 cases of type 1 diabetes were diagnosed in children 0-14 years of age. We were able to use 1,064 of these cases in a total of 2,829,020 children in this analysis. We classified mean nitrate levels in drinking water in 3,932 postal code areas in The Netherlands in 1991-1995 into two exposure categories. One category was based on equal numbers of children exposed to different nitrate levels (0.25-2.08, 2.10-6.42, and 6.44-41.19 mg/L nitrate); the other was based on cut-off values of 10 and 25 mg/L nitrate. We determined standardized incidence ratios (SIRs) for type 1 diabetes in subgroups of the 2,829,020 children with respect to both nitrate exposure categories, sex, and age and as compared in univariate analysis using the chi-square test for trend. We compared the incidence rate ratios (IRRs) by multivariate analysis in a Poisson regression model. We found an effect of increasing age of the children on incidence of type 1 diabetes, but we did not find an effect of sex or of nitrate concentration in drinking water using the two exposure categories. For nitrate levels > 25 mg/L, an increased SIR and an increased IRR of 1.46 were observed; however, this increase was not statistically significant, probably because of the small number of cases (15 of 1,064). We concluded that there is no convincing evidence that nitrate in drinking water at current exposure levels is a risk factor for childhood type 1 diabetes mellitus in The Netherlands, although a threshold value > 25 mg/L for the occurrence of this disease can not be excluded

Kinetic modelling of competition and depletion of shared miRNAs by competing endogenous RNAs

Non-conding RNAs play a key role in the post-transcriptional regulation of mRNA translation and turnover in eukaryotes. miRNAs, in particular, interact with their target RNAs through protein-mediated, sequence-specific binding, giving rise to extended and highly heterogeneous miRNA-RNA interaction networks. Within such networks, competition to bind miRNAs can generate an effective positive coupling between their targets. Competing endogenous RNAs (ceRNAs) can in turn regulate each other through miRNA-mediated crosstalk. Albeit potentially weak, ceRNA interactions can occur both dynamically, affecting e.g. the regulatory clock, and at stationarity, in which case ceRNA networks as a whole can be implicated in the composition of the cell's proteome. Many features of ceRNA interactions, including the conditions under which they become significant, can be unraveled by mathematical and in silico models. We review the understanding of the ceRNA effect obtained within such frameworks, focusing on the methods employed to quantify it, its role in the processing of gene expression noise, and how network topology can determine its reach.Comment: review article, 29 pages, 7 figure

WHO European Childhood Obesity Surveillance Initiative: School Nutrition Environment and Body Mass Index in Primary Schools

Background: Schools are important settings for the promotion of a healthy diet and sufficient physical activity and thus overweight prevention. Objective: To assess differences in school nutrition environment and body mass index (BMI) in primary schools between and within 12 European countries. Methods: Data from the World Health Organization (WHO) European Childhood Obesity Surveillance Initiative (COSI) were used (1831 and 2045 schools in 2007/2008 and 2009/2010, respectively). School personnel provided information on 18 school environmental characteristics on nutrition and physical activity. A school nutrition environment score was calculated using five nutrition-related characteristics whereby higher scores correspond to higher support for a healthy school nutrition environment. Trained field workers measured children’s weight and height; BMI-for-age (BMI/A) Z-scores were computed using the 2007 WHO growth reference and, for each school, the mean of the children’s BMI/A Z-scores was calculated. Results: Large between-country differences were found in the availability of food items on the premises (e.g., fresh fruit could be obtained in 12%-95% of schools) and school nutrition environment scores (range: 0.30-0.93). Low-score countries (Bulgaria, Czech Republic, Greece, Hungary, Latvia and Lithuania) graded less than three characteristics as supportive. High-score (=0.70) countries were Ireland, Malta, Norway, Portugal, Slovenia and Sweden. The combined absence of cold drinks containing sugar, sweet snacks and salted snacks were more observed in high-score countries than in low-score countries. Largest within-country school nutrition environment scores were found in Bulgaria, Czech Republic, Greece, Hungary, Latvia and Lithuania. All country-level BMI/A Z-scores were positive (range: 0.20-1.02), indicating higher BMI values than the 2007 WHO growth reference. With the exception of Norway and Sweden, a country-specific association between the school nutrition environment score and the school BMI/A Z-score was not observed. Conclusions: Some European countries have implemented more school policies that are supportive to a healthy nutrition environment than others. However, most countries with low school nutrition environment scores also host schools with supportive school environment policies, suggesting that a uniform school policy to tackle the “unhealthy” school nutrition environment has not been implemented at the same level throughout a country and may underline the need for harmonized school policies

Detection of Extended Red Emisson in the Diffuse Interstellar Medium

Extended Red Emission (ERE) has been detected in many dusty astrophysical objects and this raises the question: Is ERE present only in discrete objects or is it an observational feature of all dust, i.e. present in the diffuse interstellar medium? In order to answer this question, we determined the blue and red intensities of the radiation from the diffuse interstellar medium (ISM) and examined the red intensity for the presence of an excess above that expected for scattered light. The diffuse ISM blue and red intensities were obtained by subtracting the integrated star and galaxy intensities from the blue and red measurements made by the Imaging Photopolarimeter (IPP) aboard the Pioneer 10 and 11 spacecraft. The color of the diffuse ISM was found to be redder than the Pioneer intensities, contrary to that expected for scattered light (Diffuse Galactic Light [DGL]). The red DGL was calculated using the blue diffuse ISM intensities and the approximately invariant color of the DGL calculated with the DGL model. Subtracting the calculated red DGL from the red diffuse ISM intensities resulted in the detection of an excess red intensity. This represents the likely detection of ERE in the diffuse ISM since H-alpha emission cannot account for the strength of this excess and the only other known emission process applicable to the diffuse ISM is ERE. Thus, ERE appears to be a general characteristic of dust. From the correlation between N_HI and ERE intensity the ERE photon conversion efficiency was estimated at 10 +/- 3%.Comment: 44 pages (41 figures included), to be published in the ApJ, new version corrected for small error in fig. 2

Long-term follow-up after cancer rehabilitation using high-intensity resistance training: persistent improvement of physical performance and quality of life

The short-term beneficial effects of physical rehabilitation programmes after cancer treatment have been described. However, little is known regarding the long-term effects. The purpose of this study was to investigate the long-term effects of high-intensity resistance training compared with traditional recovery. A total of 68 cancer survivors who completed an 18-week resistance training programme were followed for 1 year. During the 1-year follow-up, 19 patients dropped out (14 due to recurrence of cancer). The remaining 49 patients of the intervention group were compared with a group of 22 patients treated with chemotherapy in the same period but not participating in any rehabilitation programme. Outcome measures were muscle strength, cardiopulmonary function, fatigue, and health-related quality of life. One year after completion of the rehabilitation programme, the outcome measures in the intervention group were still at the same level as immediately after rehabilitation. Muscle strength at 1 year was significantly higher in patients who completed the resistance training programme than in the comparison group. High-intensity resistance training has persistent effects on muscle strength, cardiopulmonary function, quality of life, and fatigue. Rehabilitation programmes for patients treated with chemotherapy with a curative intention should include high-intensity resistance training in their programme

Glastir Monitoring & Evaluation Programme. Second year annual report

What is the purpose of Glastir Monitoring and Evaluation Programme? Glastir is the main scheme by which the Welsh Government pays for environmental goods and services whilst the Glastir Monitoring and Evaluation Programme (GMEP) evaluates the scheme’s success. Commissioning of the monitoring programme in parallel with the launch of the Glastir scheme provides fast feedback and means payments can be modified to increase effectiveness. The Glastir scheme is jointly funded by the Welsh Government (through the Rural Development Plan) and the EU. GMEP will also support a wide range of other national and international reporting requirements. What is the GMEP approach? GMEP collects evidence for the 6 intended outcomes from the Glastir scheme which are focussed on climate change, water and soil quality, biodiversity, landscape, access and historic environment, woodland creation and management. Activities include; a national rolling monitoring programme of 1km squares; new analysis of long term data from other schemes combining with GMEP data where possible; modelling to estimate future outcomes so that adjustments can be made to maximise impact of payments; surveys to assess wider socio-economic benefits; and development of novel technologies to increase detection and efficiency of future assessments. How has GMEP progressed in this 2nd year? 90 GMEP squares were surveyed in Year 2 to add to the 60 completed in Year 1 resulting in 50% of the 300 GMEP survey squares now being completed. Squares will be revisited on a 4 year cycle providing evidence of change in response to Glastir and other pressures such as changing economics of the farm business, climate change and air pollution. This first survey cycle collects the baseline against which future changes will be assessed. This is important as GMEP work this year has demonstrated land coming into the scheme is different in some respects to land outside the scheme. Therefore, future analysis to detect impact of Glastir will be made both against the national backdrop from land outside the scheme and this baseline data from land in scheme. A wide range of analyses of longterm data has been completed for all Glastir Outcomes with the exception of landscape quality and historic features condition for which limited data is available. This has involved combining data with 2013/14 GMEP data when methods allow. Overall analysis of long term data indicates one of stability but with little evidence of improvement with the exception of headwater quality, greenhouse gas emissions and woodland area for which there has been improvement over the last 20 years. Some headline statistics include: 51% of historic features in excellent or sound condition; two thirds of public rights of way fully open and accessible; improvement in hedgerow management with 85% surveyed cut in the last 3 years but < 1% recently planted; 91% of streams had some level of modification but 60% retained good ecological quality; no change topsoil carbon content over last 25 years. What is innovative? GMEP has developed various new metrics to allow for more streamlined reporting in the future. For example a new Priority Bird species Index for Wales which combines data from 35 species indicates at least half have stable or increasing populations. The new GMEP Visual Quality Landscape Index has been tested involving over 2600 respondents. Results have demonstrated its value as an objective and repeatable method for quantifying change in visual landscape quality. A new unified peat map for Wales has been developed which has been passed to Glastir Contract Managers to improve targeting of payments when negotiating Glastir contracts. An estimate of peat soil contribution to current greenhouse gas emissions due to human modification has been calculated. Models have allowed quantification of land area helping to mitigate rainfall runoff. We are using new molecular tools to explore the effects of Glastir on soil organisms and satellite technologies to quantify e.g. small woody features and landcover change. Finally we are using a community approach to develop a consensus on how to define and report change in High Nature Value Farmland which will be reported in the Year 3 GMEP report

Randomized controlled trial of an internet-based self-guided hand exercise program to improve hand function in people with systemic sclerosis: the Scleroderma Patient-centered Intervention Network Hand Exercise Program (SPIN-HAND) trial

BACKGROUND: Systemic sclerosis (scleroderma; SSc) is a rare autoimmune connective tissue disease. Functional impairment of hands is common. The Scleroderma Patient-centered Intervention Network (SPIN)-HAND trial compared effects of offering access to an online self-guided hand exercise program to usual care on hand function (primary) and functional health outcomes (secondary) in people with SSc with at least mild hand function limitations. METHODS: The pragmatic, two-arm, parallel-group cohort multiple randomized controlled trial was embedded in the SPIN Cohort. Cohort participants with Cochin Hand Function Scale (CHFS) scores ≥ 3 and who indicated interest in using the SPIN-HAND Program were randomized (3:2 ratio) to an offer of program access or to usual care (targeted N = 586). The SPIN-HAND program consists of 4 modules that address (1) thumb flexibility and strength; (2) finger bending; (3) finger extension; and (4) wrist flexibility and strength. The primary outcome analysis compared CHFS scores 3 months post-randomization between participants offered versus not offered the program. Secondary outcomes were CHFS scores 6 months post-randomization and functional health outcomes (Patient-Reported Outcomes Measurement Information System profile version 2.0 domain scores) 3 and 6 months post-randomization. RESULTS: In total, 466 participants were randomized to intervention offer (N = 280) or usual care (N = 186). Of 280 participants offered the intervention, 170 (61%) consented to access the program. Of these, 117 (69%) viewed at least one hand exercise instruction video and 77 (45%) logged into the program website at least 3 times. In intent-to-treat analyses, CHFS scores were 1.2 points lower (95% CI − 2.8 to 0.3) for intervention compared to usual care 3 months post-randomization and 0.1 points lower (95% CI − 1.8 to 1.6 points) 6 months post-randomization. There were no statistically significant differences in other outcomes. CONCLUSION: The offer to use the SPIN-HAND Program did not improve hand function. Low offer uptake, program access, and minimal usage among those who accessed the program limited our ability to determine if using the program would improve function. To improve engagement, the program could be tested in a group format or as a resource to support care provided by a physical or occupational therapist. TRIAL REGISTRATION: NCT03419208. Registered on February 1, 2018

Treatments for people who use anabolic androgenic steroids: a scoping review.

BACKGROUND: A growing body of evidence suggests that anabolic androgenic steroids (AAS) are used globally by a diverse population with varying motivations. Evidence has increased greatly in recent years to support understanding of this form of substance use and the associated health harms, but there remains little evidence regarding interventions to support cessation and treat the consequences of use. In this scoping review, we identify and describe what is known about interventions that aim to support and achieve cessation of AAS, and treat and prevent associated health problems. METHODS: A comprehensive search strategy was developed in four bibliographic databases, supported by an iterative citation searching process to identify eligible studies. Studies of any psychological or medical treatment interventions delivered in response to non-prescribed use of AAS or an associated harm in any setting were eligible. RESULTS: In total, 109 eligible studies were identified, which included case reports representing a diverse range of disciplines and sources. Studies predominantly focussed on treatments for harms associated with AAS use, with scant evidence on interventions to support cessation of AAS use or responding to dependence. The types of conditions requiring treatment included psychiatric, neuroendocrine, hepatic, kidney, cardiovascular, musculoskeletal and infectious. There was limited evidence of engagement with users or delivery of psychosocial interventions as part of treatment for any condition, and of harm reduction interventions initiated alongside, or following, treatment. Findings were limited throughout by the case report study designs and limited information was provided. CONCLUSION: This scoping review indicates that while a range of case reports describe treatments provided to AAS users, there is scarce evidence on treating dependence, managing withdrawal, or initiating behaviour change in users in any settings. Evidence is urgently required to support the development of effective services for users and of evidence-based guidance and interventions to respond to users in a range of healthcare settings. More consistent reporting in articles of whether engagement or assessment relating to AAS was initiated, and publication within broader health- or drug-related journals, will support development of the evidence base

Terrestrialization, Miniaturization and Rates of Diversification in African Puddle Frogs (Anura: Phrynobatrachidae)

Terrestrialization, the evolution of non-aquatic oviposition, and miniaturization, the evolution of tiny adult body size, are recurring trends in amphibian evolution, but the relationships among the traits that characterize these phenomena are not well understood. Furthermore, these traits have been identified as possible “key innovations” that are predicted to increase rates of speciation in those lineages in which they evolve. We examine terrestrialization and miniaturization in sub-Saharan puddle frogs (Phrynobatrachidae) in a phylogenetic context to investigate the relationship between adaptation and diversification through time. We use relative dating techniques to ascertain if character trait shifts are associated with increased diversification rates, and we evaluate the likelihood that a single temporal event can explain the evolution of those traits. Results indicate alternate reproductive modes evolved independently in Phrynobatrachus at least seven times, including terrestrial deposition of eggs and terrestrial, non-feeding larvae. These shifts towards alternate reproductive modes are not linked to a common temporal event. Contrary to the “key innovations” hypothesis, clades that exhibit alternate reproductive modes have lower diversification rates than those that deposit eggs aquatically. Adult habitat, pedal webbing and body size have no effect on diversification rates. Though these traits putatively identified as key innovations for Phrynobatrachus do not seem to be associated with increased speciation rates, they may still provide opportunities to extend into new niches, thus increasing overall diversity