Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Statement on smoking cessation in COPD and other pulmonary diseases and in smokers with comorbidities who find it difficult to quit.

Chronic obstructive pulmonary disease (COPD), lung cancer, asthma and pulmonary tuberculosis are common pulmonary diseases that are caused or worsened by tobacco smoking. Growing observational evidence suggests that symptoms and prognosis of these conditions improve upon smoking cessation. Despite increasing numbers of (small) randomised controlled trials suggesting intensive smoking cessation treatments work in people with pulmonary diseases many patients are not given specific advice on the benefits or referred for intensive cessation treatments and, therefore, continue smoking. This is a qualitative review regarding smoking cessation in patients with COPD and other pulmonary disorders, written by a group of European Respiratory Society experts. We describe the epidemiological links between smoking and pulmonary disorders, the evidence for benefits of stopping smoking, how best to assess tobacco dependence and what interventions currently work best to help pulmonary patients quit. Finally, we describe characteristics and management of any "hardcore" smoker who finds it difficult to quit with standard approaches

Democratic performance of parties and legitimacy in Europe

This article analyses the development of legitimacy across 20 European democracies (1990-2010). The claim is that the democratic performance of parties affects levels of legitimacy. A conceptual and empirical discussion is presented to establish this relationship. Democratic performance is characterised by trusting parties to be responsive to the electorate and responsible in government. Legitimacy is defined as a composite measure representing satisfaction with parties, compliance with the rule of law as well as voter turnout and willingness to protest. The responsiveness of parties appears less representative on public concerns and governmental responsibility appears closer to party interests than to the general interest. Hence, a 'democratic deficit' seems to have emerged across Europe, manifested by more electoral volatility, new parties and alternation in government and lower survival rates of governments. This negatively affects trust in parties, parliament and government efficacy. Hence, party behaviour has not strongly contributed to political legitimacy since the 1990s. © 2014 © 2014 Taylor & Francis

The Impact of Chronic Cough:A Cross-Sectional European Survey

PURPOSE: Studies that investigate the impact of chronic cough have largely focused on patients attending secondary care. Our aim was to investigate the opinions of the wider general population across Europe. METHODS: An internet survey was made available in 12 languages on the European Lung Foundation website, between January 2012 and April 2013. RESULTS: Of 1120 respondents from 29 different European countries, 67 % were female, mean age 51 years (SD 15), median cough duration 2-5 years. The majority of respondents reported cough impacted their quality of life, mood and ability to undertake activities. Despite 72 % of respondents having visited their doctor ≥3 times, only 53 % had received a diagnosis. Asthma was the most common diagnosis (23 %). Most respondents reported limited or no effectiveness of medications. 88 % of respondents reported that they would like more information to be available on chronic cough. CONCLUSIONS: Chronic cough has a negative impact on quality of life. Further work is needed to raise awareness, promote management strategies, develop effective treatments and consider the educational and support needs of patients with chronic cough

Citizens' Confidence in Government, Parliament and Political Parties

This article explores citizens\u27 confidence in political institutions in relation to policy responsiveness within and across countries. The core premise of the mandate theory is that democratic elections deliver the median preferences in policy making to satisfy most citizens\u27 interests. Thus, citizens will display greater confidence toward their political institutions when they perceive that their preferences are pursued in policy making. Twelve consolidated and new democracies from the World Values and European Values Surveys and the Comparative Manifesto Project data sets are analyzed. The findings suggest, first, that individuals across the twelve countries display lower confidence toward political parties than toward parliament or government. Second, weak ideological attachment between individuals and the median policy-making positions in parliament lessens overall citizens\u27 confidence in political institutions. At the institutional level, citizens\u27 confidence for each political institution is most positively affected by the inclusion of the median party in policy processes. © 2017 Wiley. All rights reserved