Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Recovery and Sequence Analysis of Hepatitis A Virus from Springwater Implicated in an Outbreak of Acute Viral Hepatitis▿

An outbreak of acute hepatitis A virus in North Carolina was linked to drinking water from a contaminated shallow spring by phylogenetic analysis of hepatitis A virus (HAV) genomic sequences. Detection of HAV and fecal indicators in the water provided useful and timely information to assist with public health prevention and control measures

Erectile dysfunction and exposure to ambient Air pollution in a nationally representative cohort of older Men

Background: Little is known about the association between air pollution and erectile dysfunction (ED), a disorder occurring in 64% of men over the age of 70, and to date, no studies have been published. To address this significant knowledge gap, we explored the relationship between ED and air pollution in a group of older men who were part of the National Social Life, Health, and Aging Project (NSHAP), a nationally representative cohort study of older Americans. Methods: We obtained incident ED status and participant data for 412 men (age 57–85). Fine particulate matter (PM2.5) exposures were estimated using spatio-temporal models based on participants’ geocoded addresses, while nitrogen dioxide (NO2) and ozone (O3) concentrations were estimated using nearest measurements from the Environmental Protection Agency’s Air Quality System. The association between air pollution and incident ED (newly developed in Wave 2) was examined and logistic regression models were run with adjusted models controlling for race, education, season, smoking, obesity, diabetes, depression, and median household income of census tract. Results: We found positive, although statistically insignificant, associations between PM2.5, NO2, and O3 exposures and odds of incident ED for each of our examined exposure windows, including 1 to 7 year moving averages. Odds ratios (OR) for 1 and 7 year moving averages equaled 1.16 (95% CI: 0.87, 1.55) and 1.16 (95% CI: 0.92, 1.46), respectively, for an IQR increase in PM2.5 exposures. Observed associations were robust to model specifications and were not significantly modified by any of the examined risk factors for ED. Conclusions: We found associations between PM2.5, NO2, and O3 exposures and odds of developing ED that did not reach nominal statistical significance, although exposures to each pollutant were consistently associated with higher odds of developing ED. While more research is needed, our findings suggest a relationship between air pollutant exposure and incident cases of ED, a common condition in older men. Electronic supplementary material The online version of this article (doi:10.1186/s12940-017-0216-6) contains supplementary material, which is available to authorized users

The distributed neuronal systems supporting choice-making in real-life situations: differences between men and women when choosing groceries detected using magnetoencephalography

In this work, magnetoencephalography was used to study the temporal dynamics of neural responses in 16 subjects (eight women, eight men) choosing among different day-to-day consumer items. At short latencies ( 1500 ms) when brand knowledge is low. This is consistent with the late binding of (brand) memories and evaluation of multiple sources of information when a choice is not obvious. γ-Activity showed that women may activate larger neural networks when preference is high, suggesting that men and women exhibit different patterns of neural activity even though their overt performances are similar