The project aimed to assess stigmatized attitudes among health professionals directed towards patients with mental health problems. The Attitude to Mental Illness Questionnaire was used to assess participants' attitudes towards fictitious patients from a secure forensic hospital and patients with schizophrenia and substance use disorders. Participants were health professionals from acute and mental health settings. In total, 108 completed questionnaires were received. Participants had highly stigmatized attitudes towards patients from a forensic hospital and those with active substance use disorders. Attitudes were less stigmatized to people with substance use disorders who were recovering in remission. This suggested that health professionals have stigmatized attitudes towards an illness such as schizophrenia and this is worse towards patients from a secure hospital. The manner in which patients with substance use disorder are presented can have a significant effect on stigmatized attitudes by health professionals.

Genome-wide association studies have identified multiple novel genomic loci associated with vascular diseases. Many of these loci are common non-coding variants that affect the expression of disease-relevant genes within coronary vascular cells. To identify such genes on a genome-wide level, we performed deep transcriptomic analysis of genotyped primary human coronary artery smooth muscle cells (HCASMCs) and coronary endothelial cells (HCAECs) from the same subjects, including splicing Quantitative Trait Loci (sQTL), allelespecific expression (ASE), and colocalization analyses. We identified sQTLs for TARS2, YAP1, CFDP1, and STAT6 in HCASMCs and HCAECs, and 233 ASE genes, a subset of which are also GTEx eGenes in arterial tissues. Colocalization of GWAS association signals for coronary artery disease (CAD), migraine, stroke and abdominal aortic aneurysm with GTEx eGenes in aorta, coronary artery and tibial artery discovered novel candidate risk genes for these diseases. At the CAD and stroke locus tagged by rs2107595 we demonstrate colocalization with expression of the proximal gene TWIST1. We show that disrupting the rs2107595 locus alters TWIST1 expression and that the risk allele has increased binding of the NOTCH signaling protein RBPJ. Finally, we provide data that TWIST1 expression influences vascular SMC phenotypes, including proliferation and calcification, as a potential mechanism supporting a role for TWIST1 in CAD.

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Aims and MethodTo devise a simple technique to reduce stigmatised attitudes of the general public towards those with mental disorder (schizophrenia and substance misuse). Members of the general public (n=400) completed a questionnaire to measure stigmatised attitudes towards people with schizophrenia and substance misuse disorders. Participants were randomised to receive either a short, ‘upbeat’ leaflet with a description of a patient in remission and a photograph of a man in a business suit; or a simple description of a fictional patient. the 5-item Attitudes to Mental Illness Questionnaire (AMIQ) was used to measure the effect of the various procedures on stigmatised attitudes (score range −10 to +10).ResultsResults were received for 310 (77%) participants. the leaflet produced a large, statistically significant reduction in stigmatised attitudes towards people with opiate dependence (effect size 1.53, CI 1.23–1.82, P < 0.0001; median change 4 units) and alcohol dependence (effect size 1.41, CI 1.12–1.70, P < 0.0001; median change 4 units) but less so towards people with schizophrenia (effect size 0.54, CI 0.27–0.80, P=0.0002; median change 2 units). There was no difference between participants in respect of the control group at 4-week follow-up (233 responses received; 78% response rate).Clinical ImplicationsA short illustrated leaflet can be used to reduce stigmatised attitudes towards substance misuse disorders if patients are presented in a positive manner. This is less effective for attitudes towards people with schizophrenia, possibly because people have a more generous attitude towards patients who have overcome substance misuse disorders.

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In the present study, prone sleeping did not improve oxygenation in prematurely born infants, 32 weeks' PMA or older and with no ongoing respiratory problems. However, the infants were monitored in each position for an hour, thus it is recommended that oxygen saturation should continue to be monitored after 32 weeks' PMA to be certain that longer periods of supine sleeping are not associated with loss of lung volume and hypoxaemia.

Certain single nucleotide polymorphisms (SNPs) in genes encoding alcohol dehydrogenase (ADH) enzymes confer a significant protective effect against alcohol dependence syndrome (ADS) in East Asian populations. Recently, attention has focused on the role of these SNPs in determining ADS risk in European populations. To further elucidate these associations, SNPs of interest in ADH1B, ADH1C and the ADH1B/1C intergenic region were genotyped in a British and Irish population (ADS cases n = 1076: controls n = 1027) to assess their relative contribution to ADS risk. A highly significant, protective association was observed between the minor allele of rs1229984 in ADH1B and ADS risk [allelic P = 8.4 × 10(-6) , odds ratio (OR) = 0.26, 95 percent confidence interval, 0.14, 0.49]. Significant associations were also observed between ADS risk and the ADH1B/1C intergenic variant, rs1789891 [allelic P = 7.2 × 10(-5) , OR = 1.4 (1.2, 1.6)] and three non-synonymous SNPs rs698, rs1693482 and rs283413 in ADH1C. However, these associations were not completely independent; thus, while the ADH1B rs1229984 minor allele association was independent of those of the intergenic variant rs1789891 and the three ADH1C variants, the three ADH1C variants were not individually independent. In conclusion, the rare ADH1B rs1229984 mutation provides significant protection against ADS in this British and Irish population; other variants in the ADH gene cluster also alter ADS risk, although the strong linkage disequilibrium between SNPs at this location precluded clear identification of the variant(s) driving the associations.

Deciphering the impact of genetic variation on gene regulation is fundamental to understanding common, complex human diseases. Although histone modifications are important markers of gene regulatory elements of the genome, any specific histone modification has not been assayed in more than a few individuals in the human liver. As a result, the effects of genetic variation on histone modification states in the liver are poorly understood. Here, we generate the most comprehensive genome-wide dataset of two epigenetic marks, H3K4me3 and H3K27ac, and annotate thousands of putative regulatory elements in the human liver. We integrate these findings with genome-wide gene expression data collected from the same human liver tissues and high-resolution promoter-focused chromatin interaction maps collected from human liver-derived HepG2 cells. We demonstrate widespread functional consequences of natural genetic variation on putative regulatory element activity and gene expression levels. Leveraging these extensive datasets, we fine-map a total of 74 GWAS loci that have been associated with at least one complex phenotype. Our results reveal a repertoire of genes and regulatory mechanisms governing complex disease development and further the basic understanding of genetic and epigenetic regulation of gene expression in the human liver tissue.