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UK Biobank is a population-based cohort of half a million participants aged 40–69 years recruited between 2006 and 2010. In 2014, UK Biobank started the world's largest multi-modal imaging study, with the aim of re-inviting 100,000 participants to undergo brain, cardiac and abdominal magnetic resonance imaging, dual-energy X-ray absorptiometry and carotid ultrasound. The combination of large-scale multi-modal imaging with extensive phenotypic and genetic data offers an unprecedented resource for scientists to conduct health-related research. This article provides an in-depth overview of the imaging enhancement, including the data collected, how it is managed and processed, and future directions. Between 2014 and 2023, 100,000 UK Biobank participants are undergoing brain, heart and abdominal MRI, as well as DXA and carotid ultrasound scans. In this review, authors provide a detailed overview of the rationale for the collection of these imaging data, the procedures of data collection and management, and the future directions of the UK biobank imaging enhancement. [ABSTRACT FROM AUTHOR]

Background: Feedback of potentially serious incidental findings (PSIFs) to imaging research participants generates clinical assessment in most cases. Understanding the factors associated with increased risks of PSIFs and of serious final diagnoses may influence individuals’ decisions to participate in imaging research and will inform the design of PSIFs protocols for future research studies. We aimed to determine whether, and to what extent, socio-demographic, lifestyle, other health-related factors and PSIFs protocol are associated with detection of both a PSIF and a final diagnosis of serious disease. Methods and findings: Our cohort consisted of all UK Biobank participants who underwent imaging up to December 2015 (n = 7334, median age 63, 51.9% women). Brain, cardiac and body magnetic resonance, and dual-energy x-ray absorptiometry images from the first 1000 participants were reviewed systematically by radiologists for PSIFs. Thereafter, radiographers flagged concerning images for radiologists’ review. We classified final diagnoses as serious or not using data from participant surveys and clinical correspondence from GPs up to six months following imaging (either participant or GP correspondence, or both, were available for 93% of participants with PSIFs). We used binomial logistic regression models to investigate associations between age, sex, ethnicity, socio-economic deprivation, private healthcare use, alcohol intake, diet, physical activity, smoking, body mass index and morbidity, with both PSIFs and serious final diagnoses. Systematic radiologist review generated 13 times more PSIFs than radiographer flagging (179/1000 [17.9%] versus 104/6334 [1.6%]; age- and sex-adjusted OR 13.3 [95% confidence interval (CI) 10.3–17.1] p<0.001) and proportionally fewer serious final diagnoses (21/179 [11.7%]; 33/104 [31.7%]). Risks of both PSIFs and of serious final diagnoses increased with age (sex-adjusted ORs [95% CI] for oldest [67–79 years] versus youngest [44–58 years] participants for PSIFs and serious final diagnoses respectively: 1.59 [1.07–2.38] and 2.79 [0.86 to 9.0] for systematic radiologist review; 1.88 [1.14–3.09] and 2.99 [1.09–8.19] for radiographer flagging). No other factor was significantly associated with either PSIFs or serious final diagnoses. Our study is the largest so far to investigate the factors associated with PSIFs and serious final diagnoses, but despite this, we still may have missed some associations due to sparsity of these outcomes within our cohort and small numbers within some exposure categories. Conclusion: Risks of PSIFs and serious final diagnosis are substantially influenced by PSIFs protocol and to a lesser extent by age. As only 1/5 PSIFs represent serious disease, evidence-based PSIFs protocols are paramount to minimise over-investigation of healthy research participants and diversion of limited health services away from patients in need. [ABSTRACT FROM AUTHOR]

Background: Men and women are increasingly likely to stay sexually active into later life, but research shows that sexual activity and satisfaction decrease with increasing age. Ill health and medical treatments may affect sexual activity but there is little research on why some older people with a health problem affecting their sexual activity are satisfied with their sex life, and others are not. Methods: A mixed method study integrating data and analyses from the third British National Survey of Sexual Attitudes and Lifestyles (n = 3343 aged 55–74 years) and from follow-up in-depth interviews with 23 survey participants who reported having a health condition or taking medication affecting their sex life. Results: Overall, 26.9% of men and 17.1% of women aged 55–74 reported having a health condition that affected their sex life. Among this group, women were less likely than men to be sexually active in the previous 6 months (54.3% vs 62.0%) but just as likely to be satisfied with their sex life (41.9% vs 42.1%). In follow-up interviews, participants sometimes struggled to tease out the effects of ill health from those of advancing age. Where effects of ill health were identified, they tended to operate through the inclination and capacity to be sexually active, the practical possibilities for doing so and the limits placed on forms of sexual expression. In close relationships partners worked to establish compensatory mechanisms, but in less close relationships ill health provided an excuse to stop sex or deterred attempts to resolve difficulties. Most fundamentally, ill health may influence whether individuals have a partner with whom to have sex. Conclusion: The data show complex interactions between health, lifestyle and relationship factors that affect sexual activity/satisfaction. When dealing with sexual problems in older people, practitioners need to take account of individual lifestyle, needs and preferences. [ABSTRACT FROM AUTHOR]

Background Sexual violence is increasingly recognised as a public health issue. Information about prevalence, associated factors, and consequences for health in the population of Britain (England, Scotland, and Wales) is scarce. The third National Survey of Sexual Health Attitudes and Lifestyles (Natsal-3) is the first of the Natsal surveys to include questions about sexual violence and the first population-based survey in Britain to explore the issue outside the context of crime. Methods Between Sept 6, 2010, and Aug 31, 2012, we did a probability sample survey of women and men aged 16-74 years living in Britain. We asked participants about their experience of sex against their will since age 13 years and the circumstances surrounding the most recent occurrence. We explored associations between ever experiencing non-volitional sex and a range of sododemographic, health, and behavioural factors. We used logistic regression to estimate age-adjusted odds ratios to analyse factors associated with the occurrence of completed non-volitional sex in women and men. Findings We interviewed 15162 people. Completed non-volitional sex was reported by 9•8% (95% CI 9•0-10•5) of women and 1•4% (1•1-1•7) of men. Median age (interdecile range) at most recent occurrence was 18 years (14-32) for women and 16 years (13-30) for men. Completed non-volitional sex varied by family structure and, in women, by age, education, and area-level deprivation. It was associated with poor health, longstanding illness or disability, and treatment for mental health conditions, smoking, and use of non-prescription drugs in the past year in both sexes, and with binge drinking in women. Completed non-volitional sex was also associated with reporting of first heterosexual intercourse before 16 years of age, same-sex experience, more lifetime sexual partners, ever being diagnosed with a sexually transmitted infection, and low sexual function in both sexes, and, in women, with abortion and pregnancy outcome before 18 years of age. In most cases, the person responsible was known to the individual, although the nature of the relationship differed by age at most recent occurrence. Participants who were younger at interview were more likely to have told someone about the event and to have reported it to the police than were older participants. Interpretation These data provide the first population prevalence estimates of non-volitional sex in Britain. We showed it to be mainly an experience of young age and strongly associated with a range of adverse health outcomes in both women and men. Funding Grants from the UK Medical Research Council and the Wellcome Trust, with support from the Economic and Social Research Council and the Department of Health. [ABSTRACT FROM AUTHOR]

Given the increasingly important role the World Wide Web plays as an information source, and yet with the continuing problems that certain individuals, particularly those with disabilities and those using ‘non-standard’ Web browsing technology, it is vital that web resource providers be aware of design features which introduce barriers affecting the accessibility of on-line information.The role of the accessibility audit is seen as an important one in uncovering, describing, and explaining potential accessibility barriers present in a web site. It furthermore acts as an educational tool by raising awareness in accessible design amongst web designers and content providers in providing them with a recovery plan for improving the accessiblility of the audited resource, and potentially other resources.In 1999, the authors were commissioned to carry out accessibility audits of 11 web sites in the UK Higher Education sector. This paper discusses the development of the methodology used to carry out the audits, the findings of the audits in terms of accessibility levels of the subject sites, and feedback as a result of the auditing process. It concludes by looking at ways in which the methodology adopted may be tailored to suit specific types of web resource evaluation. [Copyright &y& Elsevier]

Background: In 2000, a 10-year Teenage Pregnancy Strategy was launched in England to reduce conceptions in women younger than 18 years and social exclusion in young parents. We used routinely collected data and data from Britain's National Surveys of Sexual Attitudes and Lifestyles (Natsal) to examine progress towards these goals.Methods: In this observational study, we used random-effects meta-regression to analyse the change in conception rates from 1994-98 to 2009-13 by top-tier local authorities in England, in relation to Teenage Pregnancy Strategy-related expenditure per head, socioeconomic deprivation, and region. Data from similar probability sample surveys: Natsal-1 (1990-91), Natsal-2 (1999-2001), and Natsal-3 (2010-12) were used to assess the prevalence of risk factors and their association with conception in women younger than 18 years in women aged 18-24 years; and the prevalence of participation in education, work, and training in young mothers.Findings: Conception rates in women younger than 18 years declined steadily from their peak in 1996-98 and more rapidly from 2007 onwards. More deprived areas and those receiving greater Teenage Pregnancy Strategy-related investment had higher rates of conception in 1994-98 and had greater declines to 2009-13. Regression analyses assessing the association between Teenage Pregnancy Strategy funding and decline in conception rates in women younger than 18 years showed an estimated reduction in the conception rate of 11.4 conceptions (95% CI 9.6-13.2; p<0.0001) per 1000 women aged 15-17 years for every £100 Teenage Pregnancy Strategy spend per head and a reduction of 8.2 conceptions (5.8-10.5; p<0.0001) after adjustment for socioeconomic deprivation and region. The association between conception in women younger than 18 years and lower socioeconomic status weakened slightly between Natsal-2 and Natsal-3. The prevalence of participation in education, work, or training among young women with a child conceived before age 18 years was low, but the odds of them doing so doubled between Natsal-2 and Natsal-3 (odds ratio 1.99, 95% CI 0.99-4.00).Interpretation: A sustained, multifaceted policy intervention involving health and education agencies, alongside other social and educational changes, has probably contributed to a substantial and accelerating decline in conceptions in women younger than 18 years in England since the late 1990s.Funding: Medical Research Council, Wellcome Trust, Economic and Social Research Council, and Department of Health. [ABSTRACT FROM AUTHOR]

Background Unplanned pregnancy is a key public health indicator. We describe the prevalence of unplanned pregnancy, and associated factors, in a general population sample in Britain (England, Scotland, and Wales). Method We did a probability sample survey, the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), of 15162 men and women aged 16-74 years in Britain, including 5686 women of child-bearing age (16-44 years) who were included in the pregnancy analysis, between Sept 6, 2010, and Aug 31, 2012. We describe the planning status of pregnancies with known outcomes in the past year, and report the annual population prevalence of unplanned pregnancy, using a validated, multicriteria, multi-outcome measure (the London Measure of Unplanned Pregnancy). We set the findings in the context of secular trends in reproductive health-related events, and patterns across the life course. Findings 9-7% of women aged 16-44 years had pregnancies with known outcome in the year before interview, of which 16 &#8226 2% (95% CI 13 &#8226 1-19 • 9) scored as unplanned, 29 &#8226 0% (25 •2-33&#8226 2) as ambivalent, and 54 • 8% (50 • 3-59 • 2) as planned, giving an annual prevalence estimate for unplanned pregnancy of 1-5% (1-2-1-9). Pregnancies in women aged 16-19 years were most commonly unplanned (45 &#8226 2% [30 • 8-60 • 5]). However, most unplanned pregnancies were in women aged 20-34 years (62-4% [50-2-73-2]). Factors strongly associated with unplanned pregnancy were first sexual intercourse before 16 years of age (age-adjusted odds ratio 2-85 [95% CI 1-77-4-57], current smoking (2-47 [1-46-4-18]), recent use of drugs other than cannabis (3-41 [1-64-7-11]), and lower educational attainment. Unplanned pregnancy was also associated with lack of sexual competence at first sexual intercourse (1 • 90 [1 • 14-3 • 08]), reporting higher frequency of sex (2 • 11 [1 &#8226 25-3 &#8226 57] for five or more times in the past 4 weeks), receiving sex education mainly from a non-school-based source (1-84 [1-12-3-00]), and current depression (1-96 [1-10-3-47]). Interpretation The increasing intervals between first sexual intercourse, cohabitation, and childbearing means that, on average, women in Britain spend about 30 years of their life needing to avert an unplanned pregnancy. Our data offer scope for primary prevention aimed at reducing the rate of unplanned conceptions, and secondary prevention aimed at modification of health behaviours and health disorders in unplanned pregnancy that might be harmful for mother and child. Funding Grants from the UK Medical Research Council and the Wellcome Trust, with support from the Economic and Social Research Council and the Department of Health. [ABSTRACT FROM AUTHOR]

Aim: To describe prevalence and trends in contraceptive method use in Britain through a comparison of the second and third National Surveys of Sexual Attitudes and Lifestyles (Natsal-2 and Natsal-3)., Methods: Cross-sectional probability sample surveys. General population sample of women aged 16-44 years, resident in Britain, with ever-experience of vaginal sex and, for analysis by sociodemographic characteristics, vaginal sex in the last year. Main outcome measure was current contraceptive method use ('usual these days'), categorised by effectiveness., Results: Prevalence of current contraceptive use among women who had ever had vaginal sex declined between Natsal-2 and Natsal-3, 83.5% (95% CI 82.4 to 84.5) and 76.4% (95% CI 75.0 to 77.7), respectively. The condom and oral contraceptive pill remain the most commonly used methods. One in five women reported use of a most effective method. While no difference was found between surveys in use of most effective methods, a decline in sterilisation use was compensated by an increase in long-acting reversible contraceptive (LARC) use. Increased LARC use was particularly evident among under-25s compared with women aged 40-44 years (OR 11.35, 95% CI 3.23 to 39.87) and a decline was observed among those with two or more children relative to those with none (OR 0.21, 95% CI 0.13 to 0.35)., Conclusions: Strategies to improve access to LARC methods have been particularly successful in increasing uptake among young people in the first decade of the 21st century. Whether this trajectory is maintained given changing sociodemographic characteristics and more recent financial cuts to sexual health service provision will warrant investigation., Competing Interests: Competing interests: RSF has received an honorarium from Natural Cycles to attend a meeting on research needs in relation to fertility awareness apps and a grant to conduct a study exploring women’s use of Natural Cycles to help with conception. AG has done consultancies for HRA-Pharma Paris. None of the other authors have any conflicts of interest., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

The relationship between magnetic resonance imaging (MRI) and clinical variables in patients suspected to have Creutzfeldt-Jakob Disease (CJD) is uncertain. We aimed to determine which MRI features of CJD (positive or negative), previously described in vivo, accurately identify CJD, are most reliably detected, vary with disease duration, and whether combined clinical and imaging features increase diagnostic accuracy for CJD. Prospective patients suspected of having CJD were referred to the National CJD Research and Surveillance Unit between 1994-2004; post-mortem, brains were sent for MRI and histopathology. Two neuroradiologists independently assessed MRI for atrophy, white matter hyperintensities, and caudate, lentiform and pulvinar signals, blind to histopathological diagnosis and clinical details. We examined differences in variable frequencies using Fisher's exact tests, and associations between variables and CJD in logistic regression models. Amongst 200 cases, 118 (59%) with a histopathological diagnosis of CJD and 82 (41%) with histopathological diagnoses other than CJD, a logistic regression model including age, disease duration at death, atrophy, white matter hyperintensities, bright or possibly bright caudate, and present pulvinar sign correctly classified 81% of cases as CJD versus not CJD. Pulvinar sign alone was not independently associated with an increased likelihood of histopathologically-confirmed CJD (of any subtype) or sporadic CJD after adjustment for age at death, disease duration, atrophy, white matter hyperintensities or caudate signal; despite the large sample, data sparsity precluded investigation of the association of pulvinar sign with variant CJD. No imaging feature varied significantly with disease duration. Of the positive CJD signs, neuroradiologists most frequently agreed on the presence or absence of atrophy (agreements in 169/200 cases [84.5%]). Combining patient age, and disease duration, with absence of atrophy and white matter hyperintensities and presence of increased caudate signal and pulvinar sign predicts CJD with good accuracy. Autopsy remains essential., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Dr. Gibson, Dr. Chappell, Dr. Summers, Dr. Collie, Professor Sellar, Professor Best and Professor Knight have nothing to disclose. Professor Ironside reports grants from Department of Health Policy Research Programme/Scottish Government, grants from Medical Research Council, personal fees from Piramal, personal fees from Covance, outside the submitted work. Professor Wardlaw reports grants from Boehringer Ingelheim, grants from Scottish Funding Council, grants from MRC, grants from Novartis, during the conduct of the study; grants from EU, grants from Wellcome Trust, grants from MRC, grants from BHF, grants from EPSRC, grants from CSO, other from GlaxoSmithKline, outside the submitted work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Epidemiological studies have provided strong evidence for a role of endogenous sex steroids in the etiology of breast cancer. Our aim was to identify common variants in genes involved in sex steroid synthesis or metabolism that are associated with hormone levels and the risk of breast cancer in premenopausal women., Methods: We measured urinary levels of estrone glucuronide (E1G) using a protocol specifically developed to account for cyclic variation in hormone levels during the menstrual cycle in 729 healthy premenopausal women. We genotyped 642 single-nucleotide polymorphisms (SNPs) in these women; a single SNP, rs10273424, was further tested for association with the risk of breast cancer using data from 10 551 breast cancer case patients and 17 535 control subjects. All statistical tests were two-sided., Results: rs10273424, which maps approximately 50 kb centromeric to the cytochrome P450 3A (CYP3A) gene cluster at chromosome 7q22.1, was associated with a 21.8% reduction in E1G levels (95% confidence interval [CI] = 27.8% to 15.3% reduction; P = 2.7 × 10(-9)) and a modest reduction in the risk of breast cancer in case patients who were diagnosed at or before age 50 years (odds ratio [OR] = 0.91, 95% CI = 0.83 to 0.99; P = .03) but not in those diagnosed after age 50 years (OR = 1.01, 95% CI = 0.93 to 1.10; P = .82)., Conclusions: Genetic variation in noncoding sequences flanking the CYP3A locus contributes to variance in premenopausal E1G levels and is associated with the risk of breast cancer in younger patients. This association may have wider implications given that the most predominantly expressed CYP3A gene, CYP3A4, is responsible for metabolism of endogenous and exogenous hormones and hormonal agents used in the treatment of breast cancer.

Background: Genome-wide association studies have identified several common genetic variants associated with breast cancer risk. It is likely, however, that a substantial proportion of such loci have not yet been discovered., Methods: We compared 296,114 tagging single-nucleotide polymorphisms in 1694 breast cancer case subjects (92% with two primary cancers or at least two affected first-degree relatives) and 2365 control subjects, with validation in three independent series totaling 11,880 case subjects and 12,487 control subjects. Odds ratios (ORs) and associated 95% confidence intervals (CIs) in each stage and all stages combined were calculated using unconditional logistic regression. Heterogeneity was evaluated with Cochran Q and I(2) statistics. All statistical tests were two-sided., Results: We identified a novel risk locus for breast cancer at 9q31.2 (rs865686: OR = 0.89, 95% CI = 0.85 to 0.92, P = 1.75 × 10(-10)). This single-nucleotide polymorphism maps to a gene desert, the nearest genes being Kruppel-like factor 4 (KLF4, 636 kb centromeric), RAD23 homolog B (RAD23B, 794 kb centromeric), and actin-like 7A (ACTL7A, 736 kb telomeric). We also identified two variants (rs3734805 and rs9383938) mapping to 6q25.1 estrogen receptor 1 (ESR1), which were associated with breast cancer in subjects of northern European ancestry (rs3734805: OR = 1.19, 95% CI = 1.11 to 1.27, P = 1.35 × 10(-7); rs9383938: OR = 1.18, 95% CI = 1.11 to 1.26, P = 1.41 × 10(-7)). A variant mapping to 10q26.13, approximately 300 kb telomeric to the established risk locus within the second intron of FGFR2, was also associated with breast cancer risk, although not at genome-wide statistical significance (rs10510102: OR = 1.12, 95% CI = 1.07 to 1.17, P = 1.58 × 10(-6))., Conclusions: These findings provide further evidence on the role of genetic variation in the etiology of breast cancer. Fine mapping will be needed to identify causal variants and to determine their functional effects.