Immediately after birth, newborn babies experience rapid colonisation by microorganisms from their mothers and the surrounding environment 1. Diseases in childhood and later in life are potentially mediated through perturbation of the infant gut microbiota colonisations 2. However, the impact of modern clinical practices, such as caesarean section delivery and antibiotic usage, on the earliest stages of gut microbiota acquisition and development during the neonatal period (≤1 month) remains controversial 3,4. Here we report disrupted maternal transmission of Bacteroides strains and high-level colonisation by healthcare-associated opportunistic pathogens, including Enterococcus, Enterobacter and Klebsiella species, in babies delivered by caesarean section (C-section), and to a lesser extent, in those delivered vaginally with maternal antibiotic prophylaxis or not breastfed during the neonatal period. Applying longitudinal sampling and whole-genome shotgun metagenomic analysis on 1,679 gut microbiotas of 772 full term, UK-hospital born babies and mothers, we demonstrate that the mode of delivery is a significant factor impacting gut microbiota composition during the neonatal period that persists into infancy (1 month-1 year). Matched large-scale culturing and whole-genome sequencing (WGS) of over 800 bacterial strains cultured from these babies identified virulence factors and clinically relevant antimicrobial resistance (AMR) in opportunistic pathogens that may predispose to opportunistic infections. Our findings highlight the critical early roles of the local environment (i.e. mother and hospital) in establishing the gut microbiota in very early life, and identifies colonisation with AMR carrying, healthcare-associated opportunistic pathogens as a previously unappreciated risk factor.

SummaryBackgroundSexual behaviour and relationships are key components of wellbeing and are affected by social norms, attitudes, and health. We present data on sexual behaviours and attitudes in Britain (England, Scotland, and Wales) from the three National Surveys of Sexual Attitudes and Lifestyles (Natsal).MethodsWe used a multistage, clustered, and stratified probability sample design. Within each of the 1727 sampled postcode sectors for Natsal-3, 30 or 36 addresses were randomly selected and then assigned to interviewers. To oversample individuals aged 16–34 years, we randomly allocated addresses to either the core sample (in which individuals aged 16–74 years were eligible) or the boost sample (in which only individuals aged 16–34 years were eligible). Interviewers visited all sampled addresses between Sept 6, 2010, and Aug 31, 2012, and randomly selected one eligible individual from each household to be invited to participate. Participants completed the survey in their own homes through computer-assisted face-to-face interviews and self-interview. We analysed data from this survey, weighted to account for unequal selection probabilities and non-response to correct for differences in sex, age group, and region according to 2011 Census figures. We then compared data from participants aged 16–44 years from Natsal-1 (1990–91), Natsal-2 (1999–2001), and Natsal-3.FindingsInterviews were completed with 15 162 participants (6293 men, 8869 women) from 26 274 eligible addresses (57·7%). 82·1% (95% CI 81·0–83·1%) of men and 77·7% (76·7–78·7%) of women reported at least one sexual partner of the opposite sex in the past year. The proportion generally decreased with age, as did the range of sexual practices with partners of the opposite sex, especially in women. The increased sexual activity and diversity reported in Natsal-2 in individuals aged 16–44 years when compared with Natsal-1 has generally been sustained in Natsal-3, but in men has generally not risen further. However, in women, the number of male sexual partners over the lifetime (age-adjusted odds ratio 1·18, 95% CI 1·08–1·28), proportion reporting ever having had a sexual experience with genital contact with another woman (1·69, 1·43–2·00), and proportion reporting at least one female sexual partner in the past 5 years (2·00, 1·59–2·51) increased in Natsal-3 compared with Natsal-2. While reported number of occasions of heterosexual intercourse in the past 4 weeks had reduced since Natsal-2, we recorded an expansion of heterosexual repertoires—particularly in oral and anal sex—over time. Acceptance of same-sex partnerships and intolerance of non-exclusivity in marriage increased in men and women in Natsal-3.InterpretationSexual lifestyles in Britain have changed substantially in the past 60 years, with changes in behaviour seeming greater in women than men. The continuation of sexual activity into later life—albeit reduced in range and frequency—emphasises that attention to sexual health and wellbeing is needed throughout the life course.FundingGrants from th...

SummaryBackgroundPopulation-based estimates of prevalence, risk distribution, and intervention uptake inform delivery of control programmes for sexually transmitted infections (STIs). We undertook the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3) after implementation of national sexual health strategies, and describe the epidemiology of four STIs in Britain (England, Scotland, and Wales) and the uptake of interventions.MethodsBetween Sept 6, 2010 and Aug 31, 2012, we did a probability sample survey of 15 162 women and men aged 16–74 years in Britain. Participants were interviewed with computer-assisted face-to-face and self-completion questionnaires. Urine from a sample of participants aged 16–44 years who reported at least one sexual partner over the lifetime was tested for the presence of Chlamydia trachomatis, type-specific human papillomavirus (HPV), Neisseria gonorrhoeae, and HIV antibody. We describe age-specific and sex-specific prevalences of infection and intervention uptake, in relation to demographic and behavioural factors, and explore changes since Natsal-1 (1990–91) and Natsal-2 (1999–2001).FindingsOf 8047 eligible participants invited to provide a urine sample, 4828 (60%) agreed. We excluded 278 samples, leaving 4550 (94%) participants with STI test results. Chlamydia prevalence was 1·5% (95% CI 1·1–2·0) in women and 1·1% (0·7–1·6) in men. Prevalences in individuals aged 16–24 years were 3·1% (2·2–4·3) in women and 2·3% (1·5–3·4) in men. Area-level deprivation and higher numbers of partners, especially without use of condoms, were risk factors. However, 60·4% (45·5–73·7) of chlamydia in women and 43·3% (25·9–62·5) in men was in individuals who had had one partner in the past year. Among sexually active 16–24-year-olds, 54·2% (51·4–56·9) of women and 34·6% (31·8–37·4) of men reported testing for chlamydia in the past year, with testing higher in those with more partners. High-risk HPV was detected in 15·9% (14·4–17·5) of women, similar to in Natsal-2. Coverage of HPV catch-up vaccination was 61·5% (58·2–64·7). Prevalence of HPV types 16 and 18 in women aged 18–20 years was lower in Natsal-3 than Natsal-2 (5·8% [3·9–8·6] vs 11·3% [6·8–18·2]; age-adjusted odds ratio 0·44 [0·21–0·94]). Gonorrhoea (<0·1% prevalence in women and men) and HIV (0·1% prevalence in women and 0·2% in men) were uncommon and restricted to participants with recognised high-risk factors. Since Natsal-2, substantial increases were noted in attendance at sexual health clinics (from 6·7% to 21·4% in women and from 7·7% to 19·6% in men) and HIV testing (from 8·7% to 27·6% in women and from 9·2% to 16·9% in men) in the past 5 years.InterpretationSTIs were distributed heterogeneously, requiring general and infection-specific interventions. Increases in testing and attendance at sexual health clinics, especially in people at highest risk, are encouraging. However, STIs persist both in individuals accessing and those not accessing services. Our findings provide empirical evidence to inform future sexual health inter...

SummaryBackgroundDespite its importance to sexual health and wellbeing, sexual function is given little attention in sexual health policy. Population-based studies are needed to understand sexual function across the life course.MethodsWe undertook a probability sample survey (the third National Survey of Sexual Attitudes and Lifestyles [Natsal-3]) of 15 162 individuals aged 16–74 years who lived in Britain (England, Scotland, and Wales). Interviews were done between Sept 6, 2010, and Aug 31, 2012. We assessed the distribution of sexual function by use of a novel validated measure (the Natsal-SF), which assessed problems with individual sexual response, sexual function in a relationship context, and self-appraisal of sex life (17 items; 16 items per gender). We assess factors associated with low sexual function (defined as the lowest quintile of distribution of Natsal-SF scores) and the distribution of components of the measure. Participants reporting one or more sexual partner in the past year were given a score on the Natsal-SF (11 690 participants). 4122 of these participants were not in a relationship for all of the past year and we employed the full information maximum likelihood method to handle missing data on four relationship items.FindingsWe obtained data for 4913 men and 6777 women for the Natsal-SF. For men and women, low sexual function was associated with increased age, and, after age-adjustment, with depression (adjusted odds ratio 3·70 [95% CI 2·90–4·72] for men and 4·11 [3·36–5·04] for women) and self-reported poor health status (2·63 [1·73–3·98] and 2·41 [1·72–3·39]). Low sexual function was also associated with experiencing the end of a relationship (1·52 [1·18–1·95] and 1·77 [1·44–2·17]), inability to talk easily about sex with a partner (2·36 [1·94–2·88] and 2·82 [2·28–3·48]), and not being happy in the relationship (2·89 [2·32–3·61] and 4·10 [3·39–4·97]). Associations were also noted with engaging in fewer than four sex acts in the past 4 weeks (3·13 [2·58–3·79] and 3·38 [2·80–4·09]), having had same sex partners (2·28 [1·56–3·35] and 1·60 [1·16–2·20]), paying for sex (in men only; 2·62 [1·46–4·71]), and higher numbers of lifetime sexual partners (in women only; 2·12 [1·68–2·67] for ten or more partners). Low sexual function was also associated with negative sexual health outcomes such as experience of non-volitional sex (1·98 [1·14–3·43] and 2·18 [1·79–2·66]) and STI diagnosis (1·50 [1·06–2·11] and 1·83 [1·35–2·47]). Among individuals reporting sex in the past year, problems with sexual response were common (41·6% of men and 51·2% of women reported one or more problem) but self-reported distress about sex lives was much less common (9·9% and 10·9%). For individuals in a sexual relationship for the past year, 23·4% of men and 27·4% of women reported an imbalance in level of interest in sex between partners, and 18·0% of men and 17·1% of women said that their partner had had sexual difficulties. Most participants who did not have sex in the past year were not dissatisfied, distressed, or avoid...

BackgroundData from the first two National Surveys of Sexual Attitudes and Lifestyles, carried out in 1990–1991 (Natsal-1) and 1999–2001 (Natsal-2), have been extensively used to inform sexual health policy in Britain over the past two decades. Natsal-3 was carried out from September 2010 to August 2012 in order to provide up-to-date measures of sexual lifestyles and to extend the scope of the previous studies by including an older age group (up to 74 years), an extended range of topics and biological measures.MethodsWe describe the methods used in Natsal-3, which surveyed the general population in Britain aged 16–74 years (with oversampling of younger adults aged 16–34 years).ResultsOverall, 15 162 interviews were completed, with a response rate of 57.7% and a cooperation rate of 65.8%. The response rate for the boost sample of ages 16–34 years was 64.8%, only marginally lower than the 65.4% achieved for Natsal-2, which surveyed a similar age range (16–44). The data were weighted by age, gender and region to reduce possible bias. Comparisons with census data show the weighted sample to provide good representation on a range of respondent characteristics. The interview involved a combination of face-to-face and self-completion components, both carried out on computer. Urine samples from 4550 sexually-experienced participants aged 16–44 years were tested for a range of STIs. Saliva samples from 4128 participants aged 18–74 years were tested for testosterone.ConclusionsNatsal-3 provides a high quality dataset that can be used to examine trends in sexual attitudes and behaviours over the past 20 years.

STUDY QUESTIONWhat is the prevalence of infertility and of help seeking among women and men in Britain?SUMMARY ANSWEROne in eight women and one in ten men aged 16–74 years had experienced infertility, defined by unsuccessfully attempting pregnancy for a year or longer, and little more than half of these people sought medical or professional help.WHAT IS KNOWN ALREADYEstimates of infertility and help seeking in Britain vary widely and are not easily comparable because of different definitions and study populations.STUDY DESIGN, SIZE, DURATIONA cross-sectional population survey was conducted between 2010 and 2012 with a sample of 15 162 women and men aged 16–74 years.PARTICIPANTS/MATERIALS, SETTING, METHODSParticipants completed the Natsal-3 questionnaire, using computer-assisted personal interviewing (CAPI) and computer-assisted self-interview (CASI).MAIN RESULTS AND THE ROLE OF CHANCEThe reported prevalence of infertility was 12.5% (CI 95% 11.7–13.3) among women and 10.1% (CI 95% 9.2–11.1) among men. Increased prevalence was associated with later cohabitation with a partner, higher socio-economic status and, for those who had a child, becoming parents at older ages. The reported prevalence of help seeking was 57.3% (CI 95% 53.6–61.0) among women and 53.2% (CI 95% 48.1–58.1) among men. Help seekers were more likely to be better educated and in higher status occupations and, among those who had a child, to have become parents later in life.LIMITATIONS, REASONS FOR CAUTIONThese data are cross-sectional so it is not possible to establish temporality or infer causality. Self-reported data may be subject to recall bias.WIDER IMPLICATIONS OF THE FINDINGSThe study provides estimates of infertility and help seeking in Britain and the results indicate that the prevalence of infertility is higher among those delaying parenthood. Those with higher educational qualifications and occupational status are more likely to consult with medical professionals for fertility problems than others and these inequalities in help seeking should be considered by clinical practice and public health.STUDY FUNDING/COMPETING INTEREST(S)Funding was provided by grants from the Medical Research Council and the Wellcome Trust, with support from the Economic and Social Research Council and the Department of Health. AMJ is a Governor of the Wellcome Trust. Other authors have no competing interests.

When expressed in heterologous cells, the viral FLIP protein (vFLIP) of Kaposi's-sarcoma-associated herpesvirus (KSHV) has been reported both to block Fas-mediated apoptosis and to activate the NF-κB activation pathway by interaction with IκB kinase (IKK). In a yeast-two-hybrid screen, we identified IKKγ as an interacting partner of vFLIP. We expressed fragments of IKKγ in mammalian cells and bacteria, and identified the central CCR3/4 (amino acids 150-272) as the vFLIP binding region. To investigate the proteins interacting with vFLIP in a KSHV-infected primary effusion lymphoma (PEL) cell line, we immunoprecipitated vFLIP and identified four associated proteins by mass spectrometry: IKK components IKKα, β and γ, and the chaperone, Hsp90. Using gel filtration chromatography, we demonstrated that a single population of vFLIP in the cytoplasm of PEL cells co-eluted and co-precipitated with an activated IKK complex. An inhibitor of Hsp90, geldanamycin, inhibited IKK's kinase activity induced by vFLIP and killed PEL cells, suggesting that vFLIP activation of IKK contributes to PEL cell survival.

Horizontal gene transfer has played a role in developing the global public health crisis of antimicrobial resistance (AMR). However, the dynamics of AMR transfer through bacterial populations and its direct impact on human disease is poorly elucidated. Here, we study parallel epidemic emergences of multiple Shigella species, a priority AMR organism, in men who have sex with men to gain insight into AMR emergence and spread. Using genomic epidemiology, we show that repeated horizontal transfer of a single AMR plasmid among Shigella enhanced existing and facilitated new epidemics. These epidemic patterns contrasted with slighter, slower increases in disease caused by organisms with vertically inherited (chromosomally encoded) AMR. This demonstrates that horizontal transfer of AMR directly affects epidemiological outcomes of globally important AMR pathogens and highlights the need for integration of genomic analyses into all areas of AMR research, surveillance and management.