Genome sequence of the button mushroom Agaricus bisporus reveals mechanisms governing adaptation to a humic-rich ecological niche

Agaricus bisporus is the model fungus for the adaptation, persistence, and growth in the humic-rich leaf-litter environment. Aside from its ecological role, A. bisporus has been an important component of the human diet for over 200 y and worldwide cultivation of the "button mushroom" forms a multibillion dollar industry. We present two A. bisporus genomes, their gene repertoires and transcript profiles on compost andduringmushroomformation.The genomes encode a full repertoire of polysaccharide-degrading enzymes similar to that of wood-decayers. Comparative transcriptomics of mycelium grown on defined medium, casing-soil, and compost revealed genes encoding enzymes involved in xylan, cellulose, pectin, and protein degradation aremore highly expressed in compost. The striking expansion of heme-thiolate peroxidases and β-etherases is distinctive from Agaricomycotina wood-decayers and suggests a broad attack on decaying lignin and related metabolites found in humic acid-rich environment. Similarly, up-regulation of these genes together with a lignolytic manganese peroxidase, multiple copper radical oxidases, and cytochrome P450s is consistent with challenges posed by complex humic-rich substrates. The gene repertoire and expression of hydrolytic enzymes in A. bisporus is substantially different from the taxonomically related ectomycorrhizal symbiont Laccaria bicolor. A common promoter motif was also identified in genes very highly expressed in humic-rich substrates. These observations reveal genetic and enzymatic mechanisms governing adaptation to the humic-rich ecological niche formed during plant degradation, further defining the critical role such fungi contribute to soil structure and carbon sequestration in terrestrial ecosystems. Genome sequence will expedite mushroom breeding for improved agronomic characteristics

Development of a Framework Structuring Themes in the Course of Adverse Drug Reactions from a Patient's Perspective

INTRODUCTION: There is a need for more extensive information about adverse drug reactions (ADRs) for patients than currently available, including information on the course of ADRs. Aspects characterising the course of ADRs from the patient perspective have not been identified before.OBJECTIVE: We aimed to develop a framework based on common themes in the course of ADRs identified from patient descriptions in patient-reported ADRs.METHODS: In this qualitative study, patient descriptions of the course of patient-reported ADRs were analysed by a thematic analysis with an inductive approach using three different existing datasets containing patient-reported ADRs. Two datasets included patient-reported ADRs from cohort event monitoring of biologics and direct oral anticoagulants and one dataset included spontaneous reports from patients concerning medication for lower urinary tract symptoms. A conceptual framework was developed from the identified main themes and subthemes.RESULTS: Patient-reported data concerning 3888 ADRs were analysed. Six main themes with multiple subthemes were identified from patient descriptions of the course of ADRs. Four themes were descriptive: frequency of an ADR episode, duration of an ADR episode, moment or period of ADR occurrence, and development in the intensity of the ADR. Two themes concerned factors influencing the course of ADRs: triggering factors and improving factors.CONCLUSIONS: The presented framework illustrates that patients describe extensive details on the course and timeframe of ADRs. The identified themes provide a basis for improving the systematic data collection of more extensive details about ADRs from patients as a first step towards the provision of more comprehensive ADR information to patients.</p

Sexual identity, attraction and behaviour in Britain: The implications of using different dimensions of sexual orientation to estimate the size of sexual minority populations and inform public health interventions.

BACKGROUND: Sexual orientation encompasses three dimensions: sexual identity, attraction and behaviour. There is increasing demand for data on sexual orientation to meet equality legislation, monitor potential inequalities and address public health needs. We present estimates of all three dimensions and their overlap in British men and women, and consider the implications for health services, research and the development and evaluation of public health interventions. METHODS: Analyses of data from Britain's third National Survey of Sexual Attitudes and Lifestyles, a probability sample survey (15,162 people aged 16-74 years) undertaken in 2010-2012. FINDINGS: A lesbian, gay or bisexual (LGB) identity was reported by 2·5% of men and 2·4% of women, whilst 6·5% of men and 11·5% of women reported any same-sex attraction and 5·5% of men and 6·1% of women reported ever experience of same-sex sex. This equates to approximately 547,000 men and 546,000 women aged 16-74 in Britain self-identifying as LGB and 1,204,000 men and 1,389,000 women ever having experience of same-sex sex. Of those reporting same-sex sex in the past 5 years, 28% of men and 45% of women identified as heterosexual. INTERPRETATION: There is large variation in the size of sexual minority populations depending on the dimension applied, with implications for the design of epidemiological studies, targeting and monitoring of public health interventions and estimating population-based denominators. There is also substantial diversity on an individual level between identity, behaviour and attraction, adding to the complexity of delivering appropriate services and interventions

Asking about Sex in General Health Surveys: Comparing the Methods and Findings of the 2010 Health Survey for England with Those of the Third National Survey of Sexual Attitudes and Lifestyles

Including questions about sexual health in the annual Health Survey for England (HSE) provides opportunities for regular measurement of key public health indicators, augmenting Britain's decennial National Survey of Sexual Attitudes and Lifestyles (Natsal). However, contextual and methodological differences may limit comparability of the findings. We examine the extent of these differences between HSE 2010 and Natsal-3 and investigate their impact on parameter estimates

Assessing local chlamydia screening performance by combining survey and administrative data to account for differences in local population characteristics

Reducing health inequalities requires improved understanding of the causes of variation. Local-level variation reflects differences in local population characteristics and health system performance. Identifying low- and high-performing localities allows investigation into these differences. We used Multilevel Regression with Post-stratification (MRP) to synthesise data from multiple sources, using chlamydia testing as our example. We used national probability survey data to identify individual-level characteristics associated with chlamydia testing and combined this with local-level census data to calculate expected levels of testing in each local authority (LA) in England, allowing us to identify LAs where observed chlamydia testing rates were lower or higher than expected, given population characteristics. Taking account of multiple covariates, including age, sex, ethnicity, student and cohabiting status, 5.4% and 3.5% of LAs had testing rates higher than expected for 95% and 99% posterior credible intervals, respectively; 60.9% and 50.8% had rates lower than expected. Residual differences between observed and MRP expected values were smallest for LAs with large proportions of non-white ethnic populations. London boroughs that were markedly different from expected MRP values (≥90% posterior exceedance probability) had actively targeted risk groups. This type of synthesis allows more refined inferences to be made at small-area levels than previously feasible

Methodology of Natsal-COVID Wave 1: a large, quasi-representative survey with qualitative follow-up measuring the impact of COVID-19 on sexual and reproductive health in Britain [version 1; peer review: awaiting peer review]

Background: Britain’s National Surveys of Sexual Attitudes and Lifestyles (Natsal) have been undertaken decennially since 1990 and provide a key data source underpinning sexual and reproductive health (SRH) policy. The COVID-19 pandemic disrupted many aspects of sexual lifestyles, triggering an urgent need for population-level data on sexual behaviour, relationships, and service use at a time when gold-standard in-person, household-based surveys with probability sampling were not feasible. We designed the Natsal-COVID study to understand the impact of COVID-19 on the nation’s SRH and assessed the sample representativeness. Methods: Natsal-COVID Wave 1 data collection was conducted four months (29/7-10/8/2020) after the announcement of Britain’s first national lockdown (23/03/2020). This was an online web-panel survey administered by survey research company, Ipsos MORI. Eligible participants were resident in Britain, aged 18-59 years, and the sample included a boost of those aged 18-29. Questions covered participants’ sexual behaviour, relationships, and SRH service use. Quotas and weighting were used to achieve a quasi-representative sample of the British general population. Participants meeting criteria of interest and agreeing to recontact were selected for qualitative follow-up interviews. Comparisons were made with contemporaneous national probability surveys and Natsal-3 (2010-12) to understand bias. Results: 6,654 participants completed the survey and 45 completed follow-up interviews. The weighted Natsal-COVID sample was similar to the general population in terms of gender, age, ethnicity, rurality, and, among sexually-active participants, numbers of sexual partners in the past year. However, the sample was more educated, contained more sexually-inexperienced people, and included more people in poorer health. Conclusions: Natsal-COVID Wave 1 rapidly collected quasi-representative population data to enable evaluation of the early population-level impact of COVID-19 and lockdown measures on SRH in Britain and inform policy. Although sampling was less representative than the decennial Natsals, Natsal-COVID will complement national surveillance data and Natsal-4 (planned for 2022)

Sexual mixing in opposite-sex partnerships in Britain and its implications for STI risk: findings from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3)

Background: The extent to which individuals are similar to their sexual partners influences STI-transmission probabilities, yet there is a dearth of empirical data, especially those representative of the population. Methods: Analyses of data reported by 10 759 sexually active people aged 16-74 y interviewed for a British national probability survey undertaken in 2010-12. Computer-assisted self-interviews asked about partner numbers and characteristics of participants' three most recent partnerships (MRPs). Opposite-sex MRPs were weighted to represent all such partnerships in the past year (N = 16 451). Estimates of disassortative age mixing (≥±5-y difference), ethnic mixing (partner of a different ethnic group) and geographical mixing (partner from a different region/country when they first met) were calculated, stratified by gender, age group and partnership status (casual/steady). Multivariable regression examined how these disassortative mixing measures were associated with STI-risk measures: condom use at first sex together at the partnership-level and, at the participant-level, STI-risk perception and reporting STI diagnoses. Results: Disassortative age mixing occurred in around one-third of opposite-sex partnerships, with men ≥5 y older in most cases, although this proportion varied by participant's gender and age group. Ethnic mixing occurred less frequently (11.3% of men's and 8.6% of women's partnerships) as did geographical mixing (14.1 and 16.3%, respectively). Disassortative mixing was more common among casual vs steady partnerships. Condom use at first sex was less likely in women's partnerships that were age-disassortative [adjusted odds ratio (AOR): 0.79, 95% confidence interval (CI): 0.69-0.95], whereas men reporting disassortative ethnic mixing were more likely to perceive themselves at STI risk (AOR: 1.76, 95% CI: 1.23-2.52) and report STI diagnoses (AOR: 2.37, 95% CI: 1.22-4.59). Conclusions: Disassortative mixing, although uncommon among opposite-sex partnerships in Britain, is independently associated with STI risk, warranting consideration in STI-prevention efforts