THE USE OF PRIVATE LANDS IN THE U.S. FOR OUTDOOR RECREATION: RESULTS OF A NATIONWIDE SURVEY

Land Economics/Use, Resource /Energy Economics and Policy,

Childhood intellectual disability and parents' mental health: integrating social, psychological and genetic influences.

BACKGROUND: Intellectual disability has a complex effect on the well-being of affected individuals and their families. Previous research has identified multiple risk and protective factors for parental mental health, including socioeconomic circumstances and child behaviour. AIMS: This study explored whether genetic cause of childhood intellectual disability contributes to parental well-being. METHOD: Children from across the UK with intellectual disability due to diverse genetic causes were recruited to the IMAGINE-ID study. Primary carers completed the Development and Well-being Assessment, including a measure of parental distress (Everyday Feeling Questionnaire). Genetic diagnoses were broadly categorised into aneuploidy, chromosomal rearrangements, copy number variants (CNVs) and single nucleotide variants. RESULTS: Compared with the UK general population, IMAGINE-ID parents (n = 888) reported significantly elevated emotional distress (Cohen's d = 0.546). Within-sample variation was related to recent life events and the perceived impact of children's difficulties. Impact was predicted by child age, physical disability, autistic characteristics and other behavioural difficulties. Genetic diagnosis also predicted impact, indirectly influencing parental well-being. Specifically, CNVs were associated with higher impact, not explained by CNV inheritance, neighbourhood deprivation or family structure. CONCLUSIONS: The mental health of parents caring for a child with intellectual disability is influenced by child and family factors, converging on parental appraisal of impact. We found that genetic aetiologies, broadly categorised, also influence impact and thereby family risks. Recognition of these risk factors could improve access to support for parents, reduce their long-term mental health needs and improve well-being of individuals with intellectual disability.This work was supported by the UK Medical Research Council (grant number G101400 to K.B.), UK Medical Research Council and Medical Research Foundation (grant number MR-N022572-1 to the IMAGINE-ID study; Principle Investigators: David H. Skuse, F Lucy Raymond, Jeremy Hall, Marianne Van den Bree, Michael J. Hall) and the Baily Thomas Charitable Trust (to K.B.)

Substrates of Factor XIII-A: roles in thrombosis and wound healing

Abstract FXIII (Factor XIII) is a Ca 2 + -dependent enzyme which forms covalent ε-(γ -glutamyl)lysine cross-links between the γ -carboxy-amine group of a glutamine residue and the ε-amino group of a lysine residue. FXIII was originally identified as a protein involved in fibrin clot stabilization; however, additional extracellular and intracellular roles for FXIII have been identified which influence thrombus resolution and tissue repair. The present review discusses the substrates of FXIIIa (activated FXIII) involved in thrombosis and wound healing with a particular focus on: (i) the influence of plasma FXIIIa on the formation of stable fibrin clots able to withstand mechanical and enzymatic breakdown through fibrin-fibrin cross-linking and cross-linking of fibrinolysis inhibitors, in particular α 2 -antiplasmin; (ii) the role of intracellular FXIIIa in clot retraction through cross-linking of platelet cytoskeleton proteins, including actin, myosin, filamin and vinculin; (iii) the role of intracellular FXIIIa in cross-linking the cytoplasmic tails of monocyte AT 1 Rs (angiotensin type 1 receptors) and potential effects on the development of atherosclerosis; and (iv) the role of FXIIIa on matrix deposition and tissue repair, including cross-linking of extracellular matrix proteins, such as fibronectin, collagen and von Willebrand factor, and the effects on matrix deposition and cell-matrix interactions. The review highlights the central role of FXIIIa in the regulation of thrombus stability, thrombus regulation, cell-matrix interactions and wound healing, which is supported by observations in FXIII-deficient humans and animals

Visualizing Alternative Phosphorus Scenarios for Future Food Security

The impact of global phosphorus scarcity on food security has increasingly been the focus of scientific studies over the past decade. However, systematic analyses of alternative futures for phosphorus supply and demand throughout the food system are still rare and provide limited inclusion of key stakeholders. Addressing global phosphorus scarcity requires an integrated approach exploring potential demand reduction as well as recycling opportunities. This implies recovering phosphorus from multiple sources, such as food waste, manure, and excreta, as well as exploring novel opportunities to reduce the long-term demand for phosphorus in food production such as changing diets. Presently, there is a lack of stakeholder and scientific consensus around priority measures. To therefore enable exploration of multiple pathways and facilitate a stakeholder dialog on the technical, behavioral, and institutional changes required to meet long-term future phosphorus demand, this paper introduces an interactive web-based tool, designed for visualizing global phosphorus scenarios in real time. The interactive global phosphorus scenario tool builds on several demand and supply side measures that can be selected and manipulated interactively by the user. It provides a platform to facilitate stakeholder dialog to plan for a soft landing and identify a suite of concrete priority options, such as investing in agricultural phosphorus use efficiency, or renewable fertilizers derived from phosphorus recovered from wastewater and food waste, to determine how phosphorus demand to meet future food security could be attained on a global scale in 2040 and 2070. This paper presents four example scenarios, including (1) the potential of full recovery of human excreta, (2) the challenge of a potential increase in non-food phosphorus demand, (3) the potential of decreased animal product consumption, and (4) the potential decrease in phosphorus demand from increased efficiency and yield gains in crop and livestock systems

Soil chemistry aspects of predicting future phosphorus requirements in Sub-Saharan Africa

Phosphorus (P) is a finite resource and critical to plant growth and therefore food security. Regional‐ and continental‐scale studies propose how much P would be required to feed the world by 2050. These indicate that sub‐Saharan Africa soils have the highest soil P deficit globally. However, the spatial heterogeneity of the P deficit caused by heterogeneous soil chemistry in the continental scale has never been addressed. We provide a combination of a broadly adopted P‐sorption model that is integrated into a highly influential, large‐scale soil phosphorus cycling model. As a result, we show significant differences between the model outputs in both the soil‐P concentrations and total P required to produce future crops for the same predicted scenarios. These results indicate the importance of soil chemistry for soil‐nutrient modelling and highlight that previous influential studies may have overestimated P required. This is particularly the case in Somalia where conventional modelling predicts twice as much P required to 2050 as our new proposed model. Plain language summary Improving food security in Sub‐Saharan Africa over the coming decades requires a dramatic increase in agricultural yields. Global yield increase has been driven by, amongst other factors, the widespread use of fertilisers including phosphorus. The use of fertilisers in Sub‐Saharan Africa is often prohibitively expensive and thus the most efficient use of phosphorus should be targeted. Soil chemistry largely controls phosphorus efficiency in agriculture, for example iron and aluminium which exist naturally in soil reduce the availability of phosphate to plants. Yet soil chemistry has not been included in several influential large‐scale modelling studies which estimate phosphorus requirements in Sub‐Saharan Africa to 2050. In this study we show that predictions of phosphorus requirement to feed the population of Sub‐Saharan Africa to 2050 can significantly change if soil chemistry is included (e.g. Somalia with up to 50% difference). Our findings are a new step towards making predictive decision‐making tool for phosphorus fertiliser management in Sub‐Saharan Africa considering the variability of soil chemistry

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Amino acid residues in five separate HLA genes can explain most of the known associations between the MHC and primary biliary cholangitis.

Primary Biliary Cholangitis (PBC) is a chronic autoimmune liver disease characterised by progressive destruction of intrahepatic bile ducts. The strongest genetic association is with HLA-DQA1*04:01, but at least three additional independent HLA haplotypes contribute to susceptibility. We used dense single nucleotide polymorphism (SNP) data in 2861 PBC cases and 8514 controls to impute classical HLA alleles and amino acid polymorphisms using state-of-the-art methodologies. We then demonstrated through stepwise regression that association in the HLA region can be largely explained by variation at five separate amino acid positions. Three-dimensional modelling of protein structures and calculation of electrostatic potentials for the implicated HLA alleles/amino acid substitutions demonstrated a correlation between the electrostatic potential of pocket P6 in HLA-DP molecules and the HLA-DPB1 alleles/amino acid substitutions conferring PBC susceptibility/protection, highlighting potential new avenues for future functional investigation

No Evidence That Genetic Variation at the Klotho Locus Is Associated With Longevity in Caucasians from the Newcastle 85+ Study and the UK Biobank

Copyright © The Author(s) 2021. The demographics of Western populations are changing, with an increase in the proportion of older adults. There is evidence to suggest that genetic factors may influence the aging process: studying these may lead to interventions to help individuals live a longer and healthier life. Evidence from several groups indicates that Klotho (KL), a gene encoding a single-pass transmembrane protein that acts as an FGF23 co-receptor, may be associated with longevity and healthy aging. We aimed to explore this area further by comparing the genotype counts in 642 long-lived individuals from the Newcastle 85+ Study with 18 295 middle-aged Newcastle-based controls from the UK Biobank to test whether variants at the KL gene locus are over- or under-represented in older individuals. If KL is associated with longevity, then we would expect the genotype counts to differ between the 2 cohorts. We found that the rs2283368 CC genotype and the rs9536338 C allele, but not the KL-VS haplotype, were associated with reaching very old age. However, these associations did not replicate in the remainder of the UK Biobank cohort. Thus, our results do not reliably support the role of KL as a longevity factor.Calico LLC (South San Francisco, California, United States); HAA is the recipient of a PhD studentship from the College of Health, Medical and Life Sciences, Brunel University London

Haplotype association analyses in resources of mixed structure using Monte Carlo testing

<p>Abstract</p> <p>Background</p> <p>Genomewide association studies have resulted in a great many genomic regions that are likely to harbor disease genes. Thorough interrogation of these specific regions is the logical next step, including regional haplotype studies to identify risk haplotypes upon which the underlying critical variants lie. Pedigrees ascertained for disease can be powerful for genetic analysis due to the cases being enriched for genetic disease. Here we present a Monte Carlo based method to perform haplotype association analysis. Our method, hapMC, allows for the analysis of full-length and sub-haplotypes, including imputation of missing data, in resources of nuclear families, general pedigrees, case-control data or mixtures thereof. Both traditional association statistics and transmission/disequilibrium statistics can be performed. The method includes a phasing algorithm that can be used in large pedigrees and optional use of pseudocontrols.</p> <p>Results</p> <p>Our new phasing algorithm substantially outperformed the standard expectation-maximization algorithm that is ignorant of pedigree structure, and hence is preferable for resources that include pedigree structure. Through simulation we show that our Monte Carlo procedure maintains the correct type 1 error rates for all resource types. Power comparisons suggest that transmission-disequilibrium statistics are superior for performing association in resources of only nuclear families. For mixed structure resources, however, the newly implemented pseudocontrol approach appears to be the best choice. Results also indicated the value of large high-risk pedigrees for association analysis, which, in the simulations considered, were comparable in power to case-control resources of the same sample size.</p> <p>Conclusions</p> <p>We propose hapMC as a valuable new tool to perform haplotype association analyses, particularly for resources of mixed structure. The availability of meta-association and haplotype-mining modules in our suite of Monte Carlo haplotype procedures adds further value to the approach.</p