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Objective: The idiopathic inflammatory myopathies (IIMs) are heterogeneous diseases thought to be initiated by immune activation in genetically predisposed individuals. We imputed variants from the ImmunoChip array using a large reference panel to fine-map associations and identify novel associations in IIM. Methods: We analyzed 2,565 Caucasian IIM patient samples collected through the Myositis Genetics Consortium (MYOGEN) and 10,260 ethnically matched control samples. We imputed 1,648,116 variants from the ImmunoChip array using the Haplotype Reference Consortium panel and conducted association analysis on IIM and clinical and serologic subgroups. Results: The HLA locus was consistently the most significantly associated region. Four non-HLA regions reached genome-wide significance, SDK2 and LINC00924 (both novel) and STAT4 in the whole IIM cohort, with evidence of independent variants in STAT4, and NAB1 in the polymyositis (PM) subgroup. We also found suggestive evidence of association with loci previously associated with other autoimmune rheumatic diseases (TEC and LTBR). We identified more significant associations than those previously reported in IIM for STAT4 and DGKQ in the total cohort, for NAB1 and FAM167A-BLK loci in PM, and for CCR5 in inclusion body myositis. We found enrichment of variants among DNase I hypersensitivity sites and histone marks associated with active transcription within blood cells. Conclusion: We found novel and strong associations in IIM and PM and localized signals to single genes and immune cell types.

Background Idiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases characterised by myositis-related autoantibodies plus infiltration of leucocytes into muscles and/or the skin, leading to the destruction of blood vessels and muscle fibres, chronic weakness and fatigue. While complement-mediated destruction of capillary endothelia is implicated in paediatric and adult dermatomyositis, the complex diversity of complement C4 in IIM pathology was unknown. Methods We elucidated the gene copy number (GCN) variations of total C4, C4A and C4B, long and short genes in 1644 Caucasian patients with IIM, plus 3526 matched healthy controls using real-time PCR or Southern blot analyses. Plasma complement levels were determined by single radial immunodiffusion. Results The large study populations helped establish the distribution patterns of various C4 GCN groups. Low GCNs of C4T (C4T=2+3) and C4A deficiency (C4A=0+1) were strongly correlated with increased risk of IIM with OR equalled to 2.58 (2.28-2.91), p=5.0×10 -53 for C4T, and 2.82 (2.48-3.21), p=7.0×10 -57 for C4A deficiency. Contingency and regression analyses showed that among patients with C4A deficiency, the presence of HLA-DR3 became insignificant as a risk factor in IIM except for inclusion body myositis (IBM), by which 98.2% had HLA-DR3 with an OR of 11.02 (1.44-84.4). Intragroup analyses of patients with IIM for C4 protein levels and IIM-related autoantibodies showed that those with anti-Jo-1 or with anti-PM/Scl had significantly lower C4 plasma concentrations than those without these autoantibodies. Conclusions C4A deficiency is relevant in dermatomyositis, HLA-DRB1∗03 is important in IBM and both C4A deficiency and HLA-DRB1∗03 contribute interactively to risk of polymyositis.

Objective: We undertook this study to examine the X chromosome complement in participants with systemic sclerosis (SSc) as well as idiopathic inflammatory myopathies. Method(s): The participants met classification criteria for the diseases. All participants underwent single-nucleotide polymorphism typing. We examined X and Y single-nucleotide polymorphism heterogeneity to determine the number of X chromosomes. For statistical comparisons, we used chi2 analyses with calculation of 95% confidence intervals. Result(s): Three of seventy men with SSc had 47,XXY (P = 0.0001 compared with control men). Among the 435 women with SSc, none had 47,XXX. Among 709 men with polymyositis or dermatomyositis (PM/DM), seven had 47,XXY (P = 0.0016), whereas among the 1783 women with PM/DM, two had 47,XXX. Of 147 men with inclusion body myositis (IBM), six had 47,XXY, and 1 of the 114 women with IBM had 47,XXX. For each of these myositis disease groups, the excess 47,XXY and/or 47,XXX was significantly higher compared with in controls as well as the known birth rate of Klinefelter syndrome or 47,XXX. Conclusion(s): Klinefelter syndrome (47,XXY) is associated with SSc and idiopathic inflammatory myopathies, similar to other autoimmune diseases with type 1 interferon pathogenesis, namely, systemic lupus erythematosus and Sjogren syndrome.Copyright © 2022 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.

Global food production and current reliance on meat-based diets requires a large share of natural resource use and causes widespread environmental pollution including phosphorus (P). Transitions to less animal-intensive diets address a suite of sustainability goals, but their impact on societys wastewater P burden is unclear. Using the UK as our example, we explored historical diet changes between 1942 and 2016, and how shifting towards plant-based diets might impact the P burden entering wastewater treatment works (WWTW), and subsequent effluent P discharge to receiving water bodies. Average daily per capita P intake declined from its peak in 1963 (1599 mg P pp(-1)d(-1)) to 1354 mg P pp(-1)d(-1)in 2016. Since 1942, the contribution of processed foods to total P consumption has increased from 21% to 52% in 2016, but consumption of total animal products has not changed significantly. Scenario analysis indicated that if individuals adopted a vegan diet or a low-meat (EAT- Lancet) diet by 2050, the P burden entering WWTW increased by 17% and 35%, respectively relative to baseline conditions in 2050. A much lower P burden increase (6%) was obtained with a flexitarian diet. An increasing burden of P to WWTW threatens greater non-compliance with regulatory targets for P discharge to water, but also presents an opportunity to the wastewater industry to recycle P in the food chain, and reduce reliance on finite phosphate rock resources. Sustainable diets that reduce food system P demand pre-consumption could also provide a source of renewable fertilizers through enhanced P recovery post-consumption and should be further explored., Funding Agencies|BBSRCBiotechnology and Biological Sciences Research Council (BBSRC); ESRCEconomic & Social Research Council (ESRC); NERCNERC Natural Environment Research Council; Scottish Government under the UK Global Food Security research programme [BB/R005842/1]

© 2019, The Author(s). The chaotic distribution and dispersal of phosphorus (P) used in food systems (defined here as disorderly disruptions to the P cycle) is harming our environment beyond acceptable limits. An analysis of P stores and flows across Europe in 2005 showed that high fertiliser P inputs relative to productive outputs was driving low system P efficiency (38 % overall). Regional P imbalance (P surplus) and system P losses were highly correlated to total system P inputs and animal densities, causing unnecessary P accumulation in soils and rivers. Reducing regional P surpluses to zero increased system P efficiency (+ 16 %) and decreased total P losses by 35 %, but required a reduction in system P inputs of ca. 40 %, largely as fertiliser. We discuss transdisciplinary and transformative solutions that tackle the P chaos by collective stakeholder actions across the entire food value chain. Lowering system P demand and better regional governance of P resources appear necessary for more efficient and sustainable food systems.

Traditional extraction methods (soil solution and solvent extraction) are simple to use and conventionally employed to assess pesticide chemical form and bioavailability in soils. However, whilst convenient for regulatory testing, it has been suggested that these approaches may be too crude or are poor predictors of bioavailability, due to their arbitrary original development to detect ‘total’ concentration using exhaustive extraction. The diffusive gradients in thin films (DGT) technique has been widely used to measure chemical speciation in situ and shown to reliably predict bioavailability of a range of contaminants (e.g. heavy metals, radionuclides, nutrients) in soil systems, because it dynamically samples contaminants from/re-supplied to the soil solution phase. Experiments were therefore conducted with 5 soils of different properties to compare DGT and the two conventional extraction approaches for sampling atrazine (ATR) and its metabolites from soils and for predicting their uptake by maize tissues. After 23 days aging, a large proportion of total ATR was still available for solvent (acetonitrile) extraction and the major constituent in soils was parent ATR. The best correlations of total ATR concentrations in maize and total ATR measured in soil were with DGT and soil solution measurements. This is encouraging, in jointly supporting one of the established methodologies traditionally used in pesticide testing (i.e. soil solution) and a widely used method (i.e. DGT), which has been validated previously for a range of contaminants. The poorer performance of solvent extraction (a procedure widely used for pesticide testing) is perhaps to be expected, given that solvents will not truly mimic the conditions encountered in soil-plant systems. © 2019 The Authors

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