Effect of vitamin D supplementation on selected inflammatory biomarkers in older adults: a secondary analysis of data from a randomised, placebo-controlled trial

Observational studies have suggested that 25-hydroxyvitamin D (25(OH)D) levels are associated with inflammatory markers. Most trials reporting significant associations between vitamin D intake and inflammatory markers used specific patient groups. Thus, we aimed to determine the effect of supplementary vitamin D using secondary data from a population-based, randomised, placebo-controlled, double-blind trial (Pilot D-Health trial 2010/0423). Participants were 60- to 84-year-old residents of one of the four eastern states of Australia. They were randomly selected from the electoral roll and were randomised to one of three trial arms: placebo (n 214), 750 μg (n 215) or 1500 μg (n 215) vitamin D3, each taken once per month for 12 months. Post-intervention blood samples for the analysis of C-reactive protein (CRP), IL-6, IL-10, leptin and adiponectin levels were available for 613 participants. Associations between intervention group and biomarker levels were evaluated using quantile regression. There were no statistically significant differences in distributions of CRP, leptin, adiponectin, leptin:adiponectin ratio or IL-10 levels between the placebo group and either supplemented group. The 75th percentile IL-6 level was 2·8 pg/ml higher (95 % CI 0·4, 5·8 pg/ml) in the 1500 μg group than in the placebo group (75th percentiles:11·0 v. 8·2 pg/ml), with a somewhat smaller, non-significant difference in 75th percentiles between the 750 μg and placebo groups. Despite large differences in serum 25(OH)D levels between the three groups after 12 months of supplementation, we found little evidence of an effect of vitamin D supplementation on cytokine or adipokine levels, with the possible exception of IL-6

Terminology and Classification of Muscle Injuries in Sport: The Munich Consensus Statement

Objective: To provide a clear terminology and classification of muscle injuries in order to facilitate effective communication among medical practitioners and development of systematic treatment strategies. Methods: Thirty native English-speaking scientists and team doctors of national and first division professional sports teams were asked to complete a questionnaire on muscle injuries to evaluate the currently used terminology of athletic muscle injury. In addition, a consensus meeting of international sports medicine experts was established to develop practical and scientific definitions of muscle injuries as well as a new and comprehensive classification system. Results: The response rate of the survey was 63%. The responses confirmed the marked variability in the use of the terminology relating to muscle injury, with the most obvious inconsistencies for the term strain. In the consensus meeting, practical and systematic terms were defined and established. In addition, a new comprehensive classification system was developed, which differentiates between four types: functional muscle disorders (type 1: overexertion-related and type 2: neuromuscular muscle disorders) describing disorders without macroscopic evidence of fibre tear and structural muscle injuries (type 3: partial tears and type 4: (sub)total tears/tendinous avulsions) with macroscopic evidence of fibre tear, that is, structural damage. Subclassifications are presented for each type. Conclusions: A consistent English terminology as well as a comprehensive classification system for athletic muscle injuries which is proven in the daily practice are presented. This will help to improve clarity of communication for diagnostic and therapeutic purposes and can serve as the basis for future comparative studies to address the continued lack of systematic information on muscle injuries in the literature. What are the new things: Consensus definitions of the terminology which is used in the field of muscle injuries as well as a new comprehensive classification system which clearly defines types of athletic muscle injuries

Global Conservation Significance of Ecuador's Yasuní National Park

Margot S. Bass is with Finding Species, Matt Finer is with Save America's Forests, Clinton N. Jenkins is with Duke University and University of Maryland, Holger Kreft is with University of California San Diego, Diego F. Cisneros-Heredia is with King's College London and Universidad San Francisco de Quito, Shawn F. McCracken is with Texas State University and the TADPOLE Organization, Nigel C. A. Pitman is with Duke University, Peter H. English is with UT Austin, Kelly Swing is with Universidad San Francisco de Quito, Gorky Villa is with Finding Species, Anthony Di Fiore is with New York University, Christian C. Voigt is with Leibniz Institute for Zoo and Wildlife Research, Thomas H. Kunz is with Boston University.Background -- The threats facing Ecuador's Yasuní National Park are emblematic of those confronting the greater western Amazon, one of the world's last high-biodiversity wilderness areas. Notably, the country's second largest untapped oil reserves—called “ITT”—lie beneath an intact, remote section of the park. The conservation significance of Yasuní may weigh heavily in upcoming state-level and international decisions, including whether to develop the oil or invest in alternatives. Methodology/Principal Findings -- We conducted the first comprehensive synthesis of biodiversity data for Yasuní. Mapping amphibian, bird, mammal, and plant distributions, we found eastern Ecuador and northern Peru to be the only regions in South America where species richness centers for all four taxonomic groups overlap. This quadruple richness center has only one viable strict protected area (IUCN levels I–IV): Yasuní. The park covers just 14% of the quadruple richness center's area, whereas active or proposed oil concessions cover 79%. Using field inventory data, we compared Yasuní's local (alpha) and landscape (gamma) diversity to other sites, in the western Amazon and globally. These analyses further suggest that Yasuní is among the most biodiverse places on Earth, with apparent world richness records for amphibians, reptiles, bats, and trees. Yasuní also protects a considerable number of threatened species and regional endemics. Conclusions/Significance -- Yasuní has outstanding global conservation significance due to its extraordinary biodiversity and potential to sustain this biodiversity in the long term because of its 1) large size and wilderness character, 2) intact large-vertebrate assemblage, 3) IUCN level-II protection status in a region lacking other strict protected areas, and 4) likelihood of maintaining wet, rainforest conditions while anticipated climate change-induced drought intensifies in the eastern Amazon. However, further oil development in Yasuní jeopardizes its conservation values. These findings form the scientific basis for policy recommendations, including stopping any new oil activities and road construction in Yasuní and creating areas off-limits to large-scale development in adjacent northern Peru.The Blue Moon Fund, the Conservation, Food & Health Foundation, and the Forrest and Frances Lattner Foundation funded MF. The US National Science Foundation (Graduate Research Fellowship Program), Texas State University-Department of Biology, and TADPOLE funded SM. The US National Science Foundation, the L.S.B. Leakey Foundation, the Wenner-Gren Foundation for Anthropological Research, and Primate Conservation, Inc. funded AD. Establishment of the Tiputini Biodiversity Station supported by the US National Science Foundation–DBI-0434875 (Thomas H. Kunz, PI, with Laura M. MacLatchy, Christopher J. Schneider, and C. Kelly Swing, Co-PIs). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Biological Sciences, School o

Explaining the effects of a multifaceted intervention to improve inpatient care in rural Kenyan hospitals -- interpretation based on retrospective examination of data from participant observation, quantitative and qualitative studies

<p>Abstract</p> <p>Background</p> <p>We have reported the results of a cluster randomized trial of rural Kenyan hospitals evaluating the effects of an intervention to introduce care based on best-practice guidelines. In parallel work we described the context of the study, explored the process and perceptions of the intervention, and undertook a discrete study on health worker motivation because this was felt likely to be an important contributor to poor performance in Kenyan public sector hospitals. Here, we use data from these multiple studies and insights gained from being participants in and observers of the intervention process to provide our explanation of how intervention effects were achieved as part of an effort to better understand implementation in low-income hospital settings.</p> <p>Methods</p> <p>Initial hypotheses were generated to explain the variation in intervention effects across place, time, and effect measure (indicator) based on our understanding of theory and informed by our implementation experience and participant observations. All data sources available for hospitals considered as cases for study were then examined to determine if hypotheses were supported, rejected, or required modification. Data included transcriptions of interviews and group discussions, field notes and that from the detailed longitudinal quantitative investigation. Potentially useful explanatory themes were identified, discussed by the implementing and research team, revised, and merged as part of an iterative process aimed at building more generic explanatory theory. At the end of this process, findings were mapped against a recently reported comprehensive framework for implementation research.</p> <p>Results</p> <p>A normative re-educative intervention approach evolved that sought to reset norms and values concerning good practice and promote 'grass-roots' participation to improve delivery of correct care. Maximal effects were achieved when this strategy and external support supervision helped create a soft-contract with senior managers clarifying roles and expectations around desired performance. This, combined with the support of facilitators acting as an expert resource and 'shop-floor' change agent, led to improvements in leadership, accountability, and resource allocation that enhanced workers' commitment and capacity and improved clinical microsystems. Provision of correct care was then particularly likely if tasks were simple and a good fit to existing professional routines. Our findings were in broad agreement with those defined as part of recent work articulating a comprehensive framework for implementation research.</p> <p>Conclusions</p> <p>Using data from multiple studies can provide valuable insight into how an intervention is working and what factors may explain variability in effects. Findings clearly suggest that major intervention strategies aimed at improving child and newborn survival in low-income settings should go well beyond the fixed inputs (training, guidelines, and job aides) that are typical of many major programmes. Strategies required to deliver good care in low-income settings should recognize that this will need to be co-produced through engagement often over prolonged periods and as part of a directive but adaptive, participatory, information-rich, and reflective process.</p

The catalytic subunit of the system L1 amino acid transporter (S<i>lc7a5</i>) facilitates nutrient signalling in mouse skeletal muscle

The System L1-type amino acid transporter mediates transport of large neutral amino acids (LNAA) in many mammalian cell-types. LNAA such as leucine are required for full activation of the mTOR-S6K signalling pathway promoting protein synthesis and cell growth. The SLC7A5 (LAT1) catalytic subunit of high-affinity System L1 functions as a glycoprotein-associated heterodimer with the multifunctional protein SLC3A2 (CD98). We generated a floxed Slc7a5 mouse strain which, when crossed with mice expressing Cre driven by a global promoter, produced Slc7a5 heterozygous knockout (Slc7a5+/-) animals with no overt phenotype, although homozygous global knockout of Slc7a5 was embryonically lethal. Muscle-specific (MCK Cre-mediated) Slc7a5 knockout (MS-Slc7a5-KO) mice were used to study the role of intracellular LNAA delivery by the SLC7A5 transporter for mTOR-S6K pathway activation in skeletal muscle. Activation of muscle mTOR-S6K (Thr389 phosphorylation) in vivo by intraperitoneal leucine injection was blunted in homozygous MS-Slc7a5-KO mice relative to wild-type animals. Dietary intake and growth rate were similar for MS-Slc7a5-KO mice and wild-type littermates fed for 10 weeks (to age 120 days) with diets containing 10%, 20% or 30% of protein. In MS-Slc7a5-KO mice, Leu and Ile concentrations in gastrocnemius muscle were reduced by ∼40% as dietary protein content was reduced from 30 to 10%. These changes were associated with >50% decrease in S6K Thr389 phosphorylation in muscles from MS-Slc7a5-KO mice, indicating reduced mTOR-S6K pathway activation, despite no significant differences in lean tissue mass between groups on the same diet. MS-Slc7a5-KO mice on 30% protein diet exhibited mild insulin resistance (e.g. reduced glucose clearance, larger gonadal adipose depots) relative to control animals. Thus, SLC7A5 modulates LNAA-dependent muscle mTOR-S6K signalling in mice, although it appears non-essential (or is sufficiently compensated by e.g. SLC7A8 (LAT2)) for maintenance of normal muscle mass

Northern grazing carbon farming – integrating production and greenhouse gas outcomes 1 : Climate Clever Beef Final Report

This project targeted three large and diverse regions across northern Australia: the Queensland Gulf, the Queensland Fitzroy Basin and the Northern Territory (Victoria River District, Douglas Daly and Barkly Tableland regions). Eleven grazing businesses across three broad regions were engaged as case studies to undertake demonstrations and evaluations within their businesses. These businesses manage more than 1,281,000 ha and 97,600 cattle. The project provided an excellent opportunity to capitalize on established networks and genuine producer interest and participation built up in recent initiatives (e.g. CCRP Climate Clever Beef (Bray et al. 2014), Northern Grazing Systems project (Phelps et al. 2014), RELRP, SCaRP, SavannaPlan, CQ Beef). The project team included research and extension professionals with decades of combined experience working with northern beef producers. The knowledge and analytical tools developed during previous projects identified practices to: reduce the greenhouse gas emissions impact of beef businesses, manage climate variability, improve land condition and increase business profitability

An exploration of cognitive subgroups in Alzheimer's disease

Heterogeneity is observed in the patterns of cognition in Alzheimer's disease (AD). Such heterogeneity might suggest the involvement of different etiological pathways or different host responses to pathology. A total of 627 subjects with mild/moderate AD underwent cognitive assessment with the Mini-Mental State Examination (MMSE) and the Dementia Rating Scale-2 (DRS-2). Latent class analysis (LCA) was performed on cognition subscale data to identify and characterize cognitive subgroups. Clinical, demographic, and genetic factors were explored for association with class membership. LCA suggested the existence of four subgroups; one group with mild and another with severe global impairment across the cognitive domains, one group with primary impairments in attention and construction, and another group with primary deficits in memory and orientation. Education, disease duration, age, Apolipoprotein E-ε4 (APOE ε4) status, gender, presence of grasp reflex, white matter changes, and early or prominent visuospatial impairment were all associated with class membership. Our results support the existence of heterogeneity in patterns of cognitive impairment in AD. Our observation of classes characterized by predominant deficits in attention/construction and memory respectively deserves further exploration as does the association between membership in the attention/construction class and APOE ε4 negative status. (JINS, 2010, 16, 233-243.

Northern grazing carbon farming – integrating production and greenhouse gas outcomes 1 : Climate Clever Beef Final Report

This project targeted three large and diverse regions across northern Australia: the Queensland Gulf, the Queensland Fitzroy Basin and the Northern Territory (Victoria River District, Douglas Daly and Barkly Tableland regions). Eleven grazing businesses across three broad regions were engaged as case studies to undertake demonstrations and evaluations within their businesses. These businesses manage more than 1,281,000 ha and 97,600 cattle. The project provided an excellent opportunity to capitalize on established networks and genuine producer interest and participation built up in recent initiatives (e.g. CCRP Climate Clever Beef (Bray et al. 2014), Northern Grazing Systems project (Phelps et al. 2014), RELRP, SCaRP, SavannaPlan, CQ Beef). The project team included research and extension professionals with decades of combined experience working with northern beef producers. The knowledge and analytical tools developed during previous projects identified practices to: reduce the greenhouse gas emissions impact of beef businesses, manage climate variability, improve land condition and increase business profitability

Strengthening health professional regulation in Kenya and Uganda : research findings policy brief

Regulation can enhance quality and safety in health care, yet the limited research on health care regulation in LMICs suggests it is often ineffective and clinical malpractice, perhaps partly consequently, widespread. We therefore need to better understand how and why health care regulation in LMICs operates and might be improved. Some research has suggested that developing, 'responsive regulation' (Ayres and Braithwaite, 1992) involving regulator-regulatee dialogue to develop and agree regulatory legitimate regulatory standards, persuade professionals to comply, and detect and sanction noncompliance, may improve regulatory effectiveness in LMICs' health care systems. Using responsive regulation as our 'theory of change', we therefore propose to research health professional regulation for doctors and nurses/midwives in Kenya and Uganda to provide evidence supporting regulators to improve health regulation and, in turn, enhance health systems and the quality and safety of patient care. As we noted, there is very little research on regulation in LMIC health systems or evidence about its impact on health care practices. We therefore propose mixed methods research, which members of the research team have previously used to research professional regulation, to develop this evidence base. This research would involve: Analysis of documentation and interviews with national regulatory stakeholders in Kenya and Uganda; focus groups with doctors and nurses/midwives in Kenya and Uganda about their experiences/perceptions of regulation; four case studies of health professional regulation at county/district level; and an online survey of Kenyan and Ugandan doctors and nurses/midwives at national level. Professionals in the Ugandan and Kenyan health systems are regulated by different profession-specific bodies but both countries are establishing single oversight bodies to monitor regulation across all health professions. These major policy changes, coupled with members of the project team's connections to regulators and health policy-makers in both countries, make this research particularly useful and timely. This foundational project aims to provide evidence to help regulators improve regulation and develop research capacity and provide a foundation for a larger research proposal, piloting regulatory improvements and evaluating their impact. Our international interdisciplinary research team contains experts on regulation, health systems improvement and health policy from Uganda, Kenya and the UK, with experience of conducting research on health systems and regulation, which has had impacted health and regulatory policy. We will collaborate closely with regulatory bodies in Kenya and Uganda throughout the project to ensure that we research issues and questions they believe are important and report findings back to regulatory stakeholders in Kenya and Uganda (at workshops in both countries) and other LMICs (via international regulatory policy and academic conferences, in publications and online) to help them improve health regulation and, in turn, the quality and safety of patient care in Kenya, Uganda and LMICs beyond