Immunogenetic Mechanisms Leading to Thyroid Autoimmunity: Recent Advances in Identifying Susceptibility Genes and Regions

The autoimmune thyroid diseases (AITD) include Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), which are characterised by a breakdown in immune tolerance to thyroid antigens. Unravelling the genetic architecture of AITD is vital to better understanding of AITD pathogenesis, required to advance therapeutic options in both disease management and prevention. The early whole-genome linkage and candidate gene association studies provided the first evidence that the HLA region and CTLA-4 represented AITD risk loci. Recent improvements in; high throughput genotyping technologies, collection of larger disease cohorts and cataloguing of genome-scale variation have facilitated genome-wide association studies and more thorough screening of candidate gene regions. This has allowed identification of many novel AITD risk genes and more detailed association mapping. The growing number of confirmed AITD susceptibility loci, implicates a number of putative disease mechanisms most of which are tightly linked with aspects of immune system function. The unprecedented advances in genetic study will allow future studies to identify further novel disease risk genes and to identify aetiological variants within specific gene regions, which will undoubtedly lead to a better understanding of AITD patho-physiology

Should we ‘hug a hoodie’? Protocol for a systematic review and meta-analysis of interventions with young people not in employment, education or training (so-called NEETs)

Background: Whilst the majority of young people succeed in education and make a positive transition to the world of work and adult life, recent statistics identify that youth comprise 40% of the world's unemployed, equating to nearly 75 million individuals. These numbers are associated with both decreased economic activity and adverse well-being, with accompanying social, health and financial costs. As a result, a wide range of providers have implemented interventions targeting this population; however, their relative effectiveness is unknown. This is exacerbated by a diverse literature base, the delivery of provision and policy across multiple sectors and disparate approaches to programme evaluation. Methods and design: We will undertake a systematic review of interventions targeting youth not in employment, education or training (NEET) populations. Only randomised and non-randomised controlled trials will be included. The objectives of the review will be to: (i) systematically review, synthesise and quality appraise experimental evidence on the effects of interventions with NEET young people, (ii) estimate effects on current NEET status, well-being and other relevant psychological and behavioural outcomes, (iii) investigate potential variation in intervention effects among sub-groups stratified by pre-trial duration of current status, socioeconomic status, gender, sub-classifications of NEET individuals and intervention components (e.g. type, frequency, duration, provider and setting) and (iv) assess the robustness of results in separate sensitivity analyses that exclude studies with higher risk of bias (e.g. in terms of study quality) or follow-up length. A rigorous literature search of English language publications post-1990 will be conducted using the following electronic databases: Medline, Embase, PsycINFO, ERIC, EPPI-Centre (Bibliomap), Social Science Citation Index, British Education Index, Conference Proceedings Index, Dissertation Abstracts, Popline and grey literature collections (e.g. GLADNET). These database searches will be supplemented with hand searching, requests for unpublished literature and website searches. Discussion: A report and executive summary will be developed by the research team with input from consultant stakeholders to aid translation of the findings into practice. The research will be disseminated at national and international conferences and submitted for peer-reviewed publication. Systematic review registration: PROSPERO CRD4201400753

Crystal structures and hydrogen bond analysis of five amino acid conjugates of terephthalic and benzene-1,2,3-tricarboxylic acids

Four linear connecting amino acid derived ligands, 1-4, and one potentially three connecting, 5, were prepared by the reaction of the appropriate terephthaloyl dichloride or benzene-1,3,5-tricarbonyl trichloride with the methyl ester protected amino acid. Amino acids used here were alanine (1, 5), isoleucine (2), leucine (3) and valine (4). Crystalline forms of four amino acid substituted terephthalamides (2,2′-(terephthaloylbis(azanediyl)) dipropanoic acid dihydrate 1; 2,2′-(terephthaloylbis(azanediyl))bis(3- methylpentanoic acid) monohydrate 2; 2,2′-(terephthaloylbis(azanediyl)) bis(4-methylpentanoic acid) dihydrate 3; 2,2′-(terephthaloylbis(azanediyl) )bis(3-methylbutanoic acid) dihydrate 4) and one benzene-1,3,5-tricarboxamide molecule (2,2′,2′′-((benzene-1,3,5-tricarbonyl)tris(azanediyl) )tripropionic acid hemihydrate 5) were characterised and the single crystal structures were solved. All the compounds form hydrogen bonded 2D and 3D nets. Linear connecting amino acid derivatives can be categorised into three groups depending on the hydrogen bond patterns and final structures. Compounds 1 and 2 form 3D structures but the final structure is different due to the different hydrogen bond synthons. Compounds 3 and 4 are isostructural and form 2D hydrogen bonded structures while 5 forms a hydrogen bonded pcu-net. Intermolecular interactions have been analysed with Hirshfeld surfaces and graph set symbols

Educating Health Professionals about Disability: A Review of Interventions

Health professionals need to understand the human rights and health needs of disabled people. This review of evidence on interventions demonstrates that a range of often innovative approaches have been trialled. Lectures by faculty are less effective in changing attitudes than contact with disabled people themselves. Existing examples of good practice need to be scaled up, and better and more long-term evaluations of impact are required

The conservation physiology toolbox: Status and opportunities

For over a century, physiological tools and techniques have been allowing researchers to characterize how organisms respond to changes in their natural environment and how they interact with human activities or infrastructure. Over time, many of these techniques have become part of the conservation physiology toolbox, which is used to monitor, predict, conserve, and restore plant and animal populations under threat. Here, we provide a summary of the tools that currently comprise the conservation physiology toolbox. By assessing patterns in articles that have been published in 'Conservation Physiology' over the past 5 years that focus on introducing, refining and validating tools, we provide an overview of where researchers are placing emphasis in terms of taxa and physiological sub-disciplines. Although there is certainly diversity across the toolbox, metrics of stress physiology (particularly glucocorticoids) and studies focusing on mammals have garnered the greatest attention, with both comprising the majority of publications ( > 45%). We also summarize the types of validations that ar

Foliar water uptake in Amazonian trees: evidence and consequences

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordThe absorption of atmospheric water directly into leaves enables plants to alleviate the water stress caused by low soil moisture, hydraulic resistance in the xylem and the effect of gravity on the water column, while enabling plants to scavenge small inputs of water from leaf-wetting events. By increasing the availability of water, and supplying it from the top of the canopy (in a direction facilitated by gravity), foliar uptake (FU) may be a significant process in determining how forests interact with climate, and could alter our interpretation of current metrics for hydraulic stress and sensitivity. FU has not been reported for lowland tropical rainforests; we test whether FU occurs in six common Amazonian tree genera in lowland Amazônia, and make a first estimation of its contribution to canopy–atmosphere water exchange. We demonstrate that FU occurs in all six genera and that dew-derived water may therefore be used to “pay” for some morning transpiration in the dry season. Using meteorological and canopy wetness data, coupled with empirically derived estimates of leaf conductance to FU (kfu), we estimate that the contribution by FU to annual transpiration at this site has a median value of 8.2% (103 mm/year) and an interquartile range of 3.4%–15.3%, with the biggest sources of uncertainty being kfu and the proportion of time the canopy is wet. Our results indicate that FU is likely to be a common strategy and may have significant implications for the Amazon carbon budget. The process of foliar water uptake may also have a profound impact on the drought tolerance of individual Amazonian trees and tree species, and on the cycling of water and carbon, regionally and globally.Natural Environment Research Council (NERC)Australian Research Council (ARC)CNPQEuropean Union FP7Royal SocietyCoordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES

The Linkages Between Photosynthesis, Productivity, Growth and Biomass in Lowland Amazonian Forests

Understanding the relationship between photosynthesis, net primary productivity and growth in forest ecosystems is key to understanding how these ecosystems will respond to global anthropogenic change, yet the linkages among these components are rarely explored in detail. We provide the first comprehensive description of the productivity, respiration and carbon allocation of contrasting lowland Amazonian forests spanning gradients in seasonal water deficit and soil fertility. Using the largest data set assembled to date, ten sites in three countries all studied with a standardized methodology, we find that (i) gross primary productivity (GPP) has a simple relationship with seasonal water deficit, but that (ii) site-to-site variations in GPP have little power in explaining site-to-site spatial variations in net primary productivity (NPP) or growth because of concomitant changes in carbon use efficiency (CUE), and conversely, the woody growth rate of a tropical forest is a very poor proxy for its productivity. Moreover, (iii) spatial patterns of biomass are much more driven by patterns of residence times (i.e. tree mortality rates) than by spatial variation in productivity or tree growth. Current theory and models of tropical forest carbon cycling under projected scenarios of global atmospheric change can benefit from advancing beyond a focus on GPP. By improving our understanding of poorly understood processes such as CUE, NPP allocation and biomass turnover times, we can provide more complete and mechanistic approaches to linking climate and tropical forest carbon cycling

Physics of Solar Prominences: II - Magnetic Structure and Dynamics

Observations and models of solar prominences are reviewed. We focus on non-eruptive prominences, and describe recent progress in four areas of prominence research: (1) magnetic structure deduced from observations and models, (2) the dynamics of prominence plasmas (formation and flows), (3) Magneto-hydrodynamic (MHD) waves in prominences and (4) the formation and large-scale patterns of the filament channels in which prominences are located. Finally, several outstanding issues in prominence research are discussed, along with observations and models required to resolve them.Comment: 75 pages, 31 pictures, review pape

Connecting Earth Observation to High-Throughput Biodiversity Data

There is much interest in using Earth Observation (EO) technology to track biodiversity, ecosystem functions, and ecosystem services, understandable given the fast pace of biodiversity loss. However, because most biodiversity is invisible to EO, EO-based indicators could be misleading, which can reduce the effectiveness of nature conservation and even unintentionally decrease conservation effort. We describe an approach that combines automated recording devices, high-throughput DNA sequencing, and modern ecological modelling to extract much more of the information available in EO data. This approach is achievable now, 62 offering efficient and near-real time monitoring of management impacts on biodiversity and its functions and services