Light drinking versus abstinence in pregnancy : behavioural and cognitive outcomes in 7-year-old children : a longitudinal cohort study

To assess whether light drinking in pregnancy is linked to unfavourable developmental outcomes in children. Design Prospective population-based cohort. Setting UK. Population Ten thousand five hundred and thirty-four 7-year-olds. Methods Quasi-experimental using propensity score matching (PSM) to compare children born to light (up to 2 units per week) and non-drinkers. Main outcome measures Behavioural difficulties rated by parents and teachers; cognitive test scores for reading, maths and spatial skills. Results Ordinary least squares (OLS) regression and PSM analyses are presented. For behavioural difficulties, unadjusted estimates for percentage standard deviation (SD) score differences ranged from 2 to 14%. On adjustment for potential confounders, differences were attenuated, with a loss of statistical significance, except for teacher-rated boys' difficulties. For boys, parent-rated behavioural difficulties: unadjusted, −11.5; OLS, −4.3; PSM, −6.8; teacher-rated behavioural difficulties: unadjusted, −13.9; OLS, −9.6; PSM, −10.8. For girls, parent-rated behavioural difficulties: unadjusted, −9.6; OLS, −2.9; PSM, −4.5; teacher-rated behavioural difficulties: unadjusted, −2.4; OLS, 4.9; PSM, 3.9. For cognitive test scores, unadjusted estimates for differences ranged between 12 and 21% of an SD score for reading, maths and spatial skills. After adjustment for potential confounders, estimates were reduced, but remained statistically significantly different for reading and for spatial skills in boys. For boys, reading: unadjusted, 20.9; OLS, 8.3; PSM, 7.3; maths: unadjusted, 14.7; OLS, 5.0; PSM, 6.5; spatial skills: unadjusted, 16.2; OLS, 7.6; PSM, 8.1. For girls, reading: unadjusted, 11.6; OLS, −0.3; PSM, −0.5; maths: unadjusted, 12.9; OLS, 4.3; PSM, 3.9; spatial skills: unadjusted, 16.2; OLS, 7.7; PSM, 6.4. Conclusion The findings suggest that light drinking during pregnancy is not linked to developmental problems in mid-childhood. These findings support current UK Department of Health guidelines on drinking during pregnancy

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

The IDENTIFY study: the investigation and detection of urological neoplasia in patients referred with suspected urinary tract cancer - a multicentre observational study

Objective To evaluate the contemporary prevalence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC] and renal cancer) in patients referred to secondary care with haematuria, adjusted for established patient risk markers and geographical variation. Patients and Methods This was an international multicentre prospective observational study. We included patients aged ≥16 years, referred to secondary care with suspected urinary tract cancer. Patients with a known or previous urological malignancy were excluded. We estimated the prevalence of bladder cancer, UTUC, renal cancer and prostate cancer; stratified by age, type of haematuria, sex, and smoking. We used a multivariable mixed-effects logistic regression to adjust cancer prevalence for age, type of haematuria, sex, smoking, hospitals, and countries. Results Of the 11 059 patients assessed for eligibility, 10 896 were included from 110 hospitals across 26 countries. The overall adjusted cancer prevalence (n = 2257) was 28.2% (95% confidence interval [CI] 22.3–34.1), bladder cancer (n = 1951) 24.7% (95% CI 19.1–30.2), UTUC (n = 128) 1.14% (95% CI 0.77–1.52), renal cancer (n = 107) 1.05% (95% CI 0.80–1.29), and prostate cancer (n = 124) 1.75% (95% CI 1.32–2.18). The odds ratios for patient risk markers in the model for all cancers were: age 1.04 (95% CI 1.03–1.05; P < 0.001), visible haematuria 3.47 (95% CI 2.90–4.15; P < 0.001), male sex 1.30 (95% CI 1.14–1.50; P < 0.001), and smoking 2.70 (95% CI 2.30–3.18; P < 0.001). Conclusions A better understanding of cancer prevalence across an international population is required to inform clinical guidelines. We are the first to report urinary tract cancer prevalence across an international population in patients referred to secondary care, adjusted for patient risk markers and geographical variation. Bladder cancer was the most prevalent disease. Visible haematuria was the strongest predictor for urinary tract cancer

GroupLens: An Open Architecture for Collaborative Filtering of Netnews

Collaborative filters help people make choices based on the opinions of other people. GroupLens is a system for collaborative filtering of netnews, to help people find articles they will like in the huge stream of available articles. News reader clients display predicted scores and make it easy for users to rate articles after they read them. Rating servers, called Better Bit Bureaus, gather and disseminate the ratings. The rating servers predict scores based on the heuristic that people who agreed in the past will probably agree again. Users can protect their privacy by entering ratings under pseudonyms, without reducing the effectiveness of the score prediction. The entire architecture is open: alternative software for news clients and Better Bit Bureaus can be developed independently and can interoperate with the components we have developed

GroupLens: An Open Architecture for Collaborative Filtering of Netnews

Collaborative filers help people make choices based on the opinions of other people. GroupLens is a system for collaborative filtering of netnews, to help people find articles they will like in the huge stream of available articles. News reader clients display predicted scores and make it easy for users to rate articles after they read them. Rating servers, called Better Bit Bureaus, gather and disseminate the ratings. The rating servers predict scores based on the heuristic that people who agreed in the past will probably agree again. Users can protect their privacy by entering ratings under a pseudonym, without reducing the effectiveness of the score prediction. The entire architecture is open: alternative software for news clients and Better Bit Bureaus can be developed independently and can interoperate with the components we have developed.