The relative influence of intellectual disabilities and autism on sensory impairments and physical disability:A whole‐country cohort of 5.3 million children and adults

Background: Intellectual disabilities and autism are lifelong and often co‐occur. Little is known on their extent of independent association with sensory impairments and physical disability. Methods: For Scotland's population, logistic regressions investigated age–gender‐adjusted odds ratios (OR) of associations, independently, of intellectual disabilities and autism with sensory impairments and physical disability. Results: 1,548,819 children/youth, and 3,746,584 adults. In children/youth, the effect size of intellectual disabilities and autism, respectively, was as follows: blindness (OR = 30.12; OR = 2.63), deafness (OR = 13.98; OR = 2.31), and physical disability (OR = 43.72; OR = 5.62). For adults, the effect size of intellectual disabilities and autism, respectively, was as follows: blindness (OR = 16.89; OR = 3.29), deafness (OR = 7.47; OR = 2.36), and physical disability (OR = 6.04; OR = 3.16). Conclusions: Intellectual disabilities have greater association with the population burden of sensory impairments/physical disability, but autism is also associated regardless of overlap with intellectual disabilities. These may impact further on communication limitations due to autism and intellectual disabilities, increasing complexity of assessments/management of other health conditions. Clinicians need to be aware of these important issues

A pragmatic harm reduction approach to manage a large outbreak of wound botulism in people who inject drugs, Scotland 2015

Abstract Background People who inject drugs (PWID) are at an increased risk of wound botulism, a potentially fatal acute paralytic illness. During the first 6 months of 2015, a large outbreak of wound botulism was confirmed among PWID in Scotland, which resulted in the largest outbreak in Europe to date. Methods A multidisciplinary Incident Management Team (IMT) was convened to conduct an outbreak investigation, which consisted of enhanced surveillance of cases in order to characterise risk factors and identify potential sources of infection. Results Between the 24th of December 2014 and the 30th of May 2015, a total of 40 cases were reported across six regions in Scotland. The majority of the cases were male, over 30 and residents in Glasgow. All epidemiological evidence suggested a contaminated batch of heroin or cutting agent as the source of the outbreak. There are significant challenges associated with managing an outbreak among PWID, given their vulnerability and complex addiction needs. Thus, a pragmatic harm reduction approach was adopted which focused on reducing the risk of infection for those who continued to inject and limited consequences for those who got infected. Conclusions The management of this outbreak highlighted the importance and need for pragmatic harm reduction interventions which support the addiction needs of PWID during an outbreak of spore-forming bacteria. Given the scale of this outbreak, the experimental learning gained during this and similar outbreaks involving spore-forming bacteria in the UK was collated into national guidance to improve the management and investigation of future outbreaks among PWID

A global surveillance system for crop diseases

To satisfy a growing demand for food, global agricultural production must increase by 70% by 2050. However, pests and crop diseases put global food supplies at risk. Worldwide, yield losses caused by pests and diseases are estimated to average 21.5% in wheat, 30.0% in rice, 22.6% in maize, 17.2% in potato, and 21.4% in soybean (1); these crops account for half of the global human calorie intake (2). Climate change and global trade drive the distribution, host range, and impact of plant diseases (3), many of which can spread or reemerge after having been under control (4). Though many national and regional plant protection organizations (NPPOs and RPPOs) work to monitor and contain crop disease outbreaks, many countries, particularly low-income countries (LICs), do not efficiently exchange information, delaying coordinated responses to prevent disease establishment and spread. To improve responses to unexpected crop disease spread, we propose a Global Surveillance System (GSS) that will extend and adapt established biosecurity practices and networking facilities into LICs, enabling countries and regions to quickly respond to emerging disease outbreaks to stabilize food supplies, enhancing global food protection

A saturated map of common genetic variants associated with human height

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes(1). Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel(2)) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries. A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.Peer reviewe

Transcriptional responses of Pseudomonas syringae to growth in epiphytic versus apoplastic leaf sites

Some strains of the foliar pathogen Pseudomonas syringae are adapted for growth and survival on leaf surfaces and in the leaf interior. Global transcriptome profiling was used to evaluate if these two habitats offer distinct environments for bacteria and thus present distinct driving forces for adaptation. The transcript profiles of Pseudomonas syringae pv. syringae B728a support a model in which leaf surface, or epiphytic, sites specifically favor flagellar motility, swarming motility based on 3-(3-hydroxyalkanoyloxy)alkanoic acid surfactant production, chemosensing, and chemotaxis, indicating active relocation primarily on the leaf surface. Epiphytic sites also promote high transcript levels for phenylalanine degradation, which may help counteract phenylpropanoid-based defenses before leaf entry. In contrast, intercellular, or apoplastic, sites favor the high-level expression of genes for GABA metabolism (degradation of these genes would attenuate GABA repression of virulence) and the synthesis of phytotoxins, two additional secondary metabolites, and syringolin A. These findings support roles for these compounds in virulence, including a role for syringolin A in suppressing defense responses beyond stomatal closure. A comparison of the transcriptomes from in planta cells and from cells exposed to osmotic stress, oxidative stress, and iron and nitrogen limitation indicated that water availability, in particular, was limited in both leaf habitats but was more severely limited in the apoplast than on the leaf surface under the conditions tested. These findings contribute to a coherent model of the adaptations of this widespread bacterial phytopathogen to distinct habitats within its host

Volunteerism, social context and health impacts: a qualitative study of Glasgow Commonwealth Games event volunteers

Volunteer engagement is crucial to the effective delivery of mega-sporting events. While evidence points to reported motivations and wellbeing benefits for individual participants during and post event, there is less evidence on how this type of civic participation relates to the social context in which it occurs and the wider social determinants of health. This qualitative study sought to understand impacts on wellbeing and the determinants of health resulting from the experience of volunteering at the Glasgow 2014 Commonwealth Games. Focus groups and interviews were conducted one-year post-Games to gather the perspectives of 46 volunteers and 7 unsuccessful applicants on their experiences. Participants provided insight into the volunteer journey, contributions and associated outcomes. Wider social impacts were also reported including a renewed sense of pride in the city. The qualitative analysis suggested an important non-linear relationship between volunteer contributions, impacts and rewards, and the outcome of enhanced social connections. The emergent ‘people and place’ framework identifies some critical factors around city life and volunteer assets that planners could consider in developing and evaluating sustainable volunteering and its wider impacts beyond a mega-event

RNA-seq Analysis Reveals That an ECF σ Factor, AcsS, Regulates Achromobactin Biosynthesis in Pseudomonas syringae pv. syringae B728a

Iron is an essential micronutrient for Pseudomonas syringae pv. syringae strain B728a and many other microorganisms; therefore, B728a has evolved methods of iron acquirement including the use of iron-chelating siderophores. In this study an extracytoplasmic function (ECF) sigma factor, AcsS, encoded within the achromobactin gene cluster is shown to be a major regulator of genes involved in the biosynthesis and secretion of this siderophore. However, production of achromobactin was not completely abrogated in the deletion mutant, implying that other regulators may be involved such as PvdS, the sigma factor that regulates pyoverdine biosynthesis. RNA-seq analysis identified 287 genes that are differentially expressed between the AcsS deletion mutant and the wild type strain. These genes are involved in iron response, secretion, extracellular polysaccharide production, and cell motility. Thus, the transcriptome analysis supports a role for AcsS in the regulation of achromobactin production and the potential activity of both AcsS and achromobactin in the plant-associated lifestyle of strain B728a

Multidisciplinary investigations of the diets of two post-medieval populations from London using stable isotopes and microdebris analysis

This paper presents the first multi-tissue study of diet in post-medieval London using both the stable light isotope analysis of carbon and nitrogen and analysis of microdebris in dental calculus. Dietary intake was explored over short and long timescales. Bulk bone collagen was analysed from humans from the Queen’s Chapel of the Savoy (QCS) (n = 66) and the St Barnabas/St Mary Abbots (SB) (n = 25). Incremental dentine analysis was performed on the second molar of individual QCS1123 to explore childhood dietary intake. Bulk hair samples (n = 4) were sampled from adults from QCS, and dental calculus was analysed from four other individuals using microscopy. In addition, bone collagen from a total of 46 animals from QCS (n = 11) and the additional site of Prescot Street (n = 35) was analysed, providing the first animal dietary baseline for post-medieval London. Overall, isotopic results suggest a largely C3-based terrestrial diet for both populations, with the exception of QCS1123 who exhibited values consistent with the consumption of C4 food sources throughout childhood and adulthood. The differences exhibited in δ15Ncoll across both populations likely reflect variations in diet due to social class and occupation, with individuals from SB likely representing wealthier individuals consuming larger quantities of animal and marine fish protein. Microdebris analysis results were limited but indicate the consumption of domestic cereals. This paper demonstrates the utility of a multidisciplinary approach to investigate diet across long and short timescales to further our understanding of variations in social status and mobility

Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis

Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1 alpha and IL-1 beta); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0.22 SD (95% CI 0.18-0.25; 12.5%; p=9.3 x 10(-33)), concentrations of interleukin 6 decreased by 0.02 SD (-0.04 to -0.01; -1,7%; p=3.5 x 10(-3)), and concentrations of C-reactive protein decreased by 0.03 SD (-0.04 to -0.02; -3.4%; p=7.7 x 10(-14)). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1.15 (1.08-1.22; p=1.8 x 10(-6)) compared with people who carried no IL-1Ra-raising alleles; the per-allele odds ratio for coronary heart disease was 1.03 (1.02-1.04; p=3.9 x 10(-10)). Perallele odds ratios were 0.97 (0.95-0.99; p=9.9 x 10(-4)) for rheumatoid arthritis, 0.99 (0.97-1.01; p=0.47) for type 2 diabetes, 1.00 (0.98-1.02; p=0.92) for ischaemic stroke, and 1.08 (1.04-1.12; p=1.8 x 10(-5)) for abdominal aortic aneurysm. In exploratory analyses, we observed per-allele increases in concentrations of proatherogenic lipids, including LDL-cholesterol, but no clear evidence of association for blood pressure, glycaemic traits, or any of the 24 other disorders studied. Modelling suggested that the observed increase in LDL-cholesterol could account for about a third of the association observed between the genetic score and increased coronary risk. Interpretation Human genetic data suggest that long-term dual IL-1 alpha/beta inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. Copyright (C) The Interleukin 1 Genetics Consortium. Open Access article distributed under the terms of CC-BY-NC-ND