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Introduction There is inconsistent evidence on the associations of sleep duration and daytime napping with dementia risk. Methods In the Million Women Study, a total of 830,716 women (mean age, 60 years) were asked about sleep duration (8 hours) and daytime napping (rarely/never, sometimes, usually) in median year 2001, and were followed for the first hospital record with any mention of dementia. Cox regression estimated dementia detection risk ratios (RRs) during 17-year follow-up in 5-year intervals. Results With 34,576 dementia cases, there was strong attenuation over follow-up in the RRs related to long sleep duration (>8 vs 7–8 hours) and usually napping (vs rarely/never). Short sleep duration was modestly, positively associated with dementia in the long term (RR = 1.08, 95% confidence interval [CI] 1.04–1.12). Discussion There was little evidence to suggest that long sleep duration and regular napping are associated with long-term dementia risk. Short sleep duration was modestly associated with dementia risk, but residual confounding cannot be excluded.

Chorus waves play an important role in the dynamic evolution of energetic electrons in the Earth’s radiation belts and ring current. Due to the orbit limitation of Van Allen Probes, our previous chorus wave model developed using Van Allen Probe data is limited to low latitude. In this study, we extend the chorus wave model to higher latitudes by combining measurements from the Van Allen Probes and Arase satellite. As a first step, we intercalibrate chorus wave measurements by comparing statistical features of chorus wave observations from Van Allen Probes and Arase missions. We first investigate the measurements in the same latitude range during the two years of overlap between the Van Allen Probe data and the Arase data. We find that the statistical intensity of chorus waves from Van Allen Probes is stronger than those from Arase observations. After the intercalibration, we combine the chorus wave measurements from the two satellite missions and develop an analytical chorus wave model which covers all magnetic local time and extends to higher latitudes. This chorus wave model will be further used in radiation belt and ring current simulations., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

Background Current or recent use of combined oral contraceptives (containing oestrogen+progestagen) has been associated with a small increase in breast cancer risk. Progestagen-only contraceptive use is increasing, but information on associated risks is limited. We aimed to assess breast cancer risk associated with current or recent use of different types of hormonal contraceptives in premenopausal women, with particular emphasis on progestagen-only preparations. Methods and findings Hormonal contraceptive prescriptions recorded prospectively in a UK primary care database (Clinical Practice Research Datalink [CPRD]) were compared in a nested case–control study for 9,498 women aged Overall, 44% (4,195/9,498) of women with breast cancer and 39% (7,092/18,171) of matched controls had a hormonal contraceptive prescription an average of 3.1 (SD 3.7) years before breast cancer diagnosis (or equivalent date for controls). About half the prescriptions were for progestagen-only preparations. Breast cancer ORs were similarly and significantly raised if the last hormonal contraceptive prescription was for oral combined, oral progestagen-only, injected progestagen, or progestagen-releasing intrauterine devices (IUDs): ORs = 1.23 (95% CI [1.14 to 1.32]; p < 0.001), 1.26 (95% CI [1.16 to 1.37]; p < 0.001), 1.25 (95% CI [1.07 to 1.45]; p = 0.004), and 1.32 (95% CI [1.17 to 1.49]; p < 0.001), respectively. Our meta-analyses yielded significantly raised relative risks (RRs) for current or recent use of progestagen-only contraceptives: oral = 1.29 (95% CI [1.21 to 1.37]; heterogeneity χ25 = 6.7; p = 0.2), injected = 1.18 (95% CI [1.07 to 1.30]; heterogeneity χ28 = 22.5; p = 0.004), implanted = 1.28 (95% CI [1.08 to 1.51]; heterogeneity χ23 = 7.3; p = 0.06), and IUDs = 1.21 (95% CI [1.14 to 1.28]; heterogeneity χ24 = 7.9; p = 0.1). When the CPRD results were combined with those from previous published findings (which included women from a wider age range), the resulting 15-year absolute excess risk associated with 5 years use of oral combined or progestagen-only contraceptives in high-income countries was estimated at: 8 per 100,000 users from age 16 to 20 years and 265 per 100,000 users from age 35 to 39 years. The main limitation of the study design was that, due to the nature of the CPRD data and most other prescription databases, information on contraceptive use was recorded during a defined period only, with information before entry into the database generally being unavailable. This means that although our findings provide evidence about the short-term associations between hormonal contraceptives and breast cancer risk, they do not provide information regarding longer-term associations, or the impact of total duration of contraceptive use on breast cancer risk. Conclusions This study provides important new evidence that current or recent use of progestagen-only contraceptives is associated with a slight increase in breast cancer risk, which does not appear to vary by mode of delivery, and is similar in magnitude to that associated with combined hormonal contraceptives. Given that the underlying risk of breast cancer increases with advancing age, the absolute excess risk associated with use of either type of oral contraceptive is estimated to be smaller in women who use it at younger rather than at older ages. Such risks need be balanced against the benefits of using contraceptives during the childbearing years.

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. Methods: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits and collated via case report forms. Results: In total, 956 patients with CTEPH were included in the analysis. The most common AEs in these patients were peripheral edema/edema (11.7%), dizziness (7.5%), right ventricular (RV)/cardiac failure (7.7%), and pneumonia (5.0%). The most common SAEs were RV/cardiac failure (7.4%), pneumonia (4.1%), dyspnea (3.6%), and syncope (2.5%). Exposure-adjusted rates of hemoptysis/pulmonary hemorrhage and hypotension were low and comparable to those in the long-term extension study of riociguat (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase–Stimulator Trial [CHEST-2]). Conclusion: Data from EXPERT show that in patients with CTEPH, the safety of riociguat in routine practice was consistent with the known safety profile of the drug, and no new safety concerns were identified. © 2020 The Authors

In situ electron density profiles obtained from Arase in the night magnetic local time (MLT) sector and from RBSP‐B covering all MLTs are used to study the small‐scale density irregularities present in the plasmasphere and near the plasmapause. Electron density perturbations with amplitudes >10% from background density and with time‐scales less than 30‐min are investigated here as the small‐scale density irregularities. The statistical survey of the density irregularities is carried out using nearly 2 years of density data obtained from RBSP‐B and 4 months of data from Arase satellites. The results show that density irregularities are present globally at all MLT sectors and L‐shells both inside and outside the plasmapause, with a higher occurrence at L > 4. The occurrence of density irregularities is found to be higher during disturbed geomagnetic and interplanetary conditions. The case studies presented here revealed: (1) The plasmaspheric density irregularities observed during both quiet and disturbed conditions are found to coexist with the hot plasma sheet population. (2) During quiet periods, the plasma waves in the whistler‐mode frequency range are found to be modulated by the small‐scale density irregularities, with density depletions coinciding well with the decrease in whistler intensity. Our observations suggest that different source mechanisms are responsible for the generation of density structures at different MLTs and geomagnetic conditions.

Flux enhancements of field-aligned low-energy O^+ ion (FALEO) are simultaneously observed by Arase, Van Allen Probes A and B in the nightside inner magnetosphere during 05–07 UT on September 22, 2018. FALEOs appear after a magnetic dipolarization signature with approximately 6–20 min delay. It has the energy-dispersion signature from a few keV to ∼100 eV only in the direction parallel to the magnetic field at Arase, while it decreases its energy from a few keV down to 10 eV in both the parallel and antiparallel directions at Probes A and B. We perform a numerical simulation to trace trajectories of test O^+ ions in a model magnetosphere, which are launched from above the ionosphere 3–15 min after a substorm. Flying virtual satellites that have the same orbits as the real satellites, we create virtual energy-time spectrograms of O^+ ions to compare with the observed ones. Results show a very good correspondence between them, indicating that FALEOs originate from ionospheric O^+ ions that are extracted from the upper ionosphere at substorm onset and flow along the magnetic field toward the geomagnetic equator. It is also revealed that 3–9 hr after their launch, test O^+ ions less than 400 eV have a spatial distribution in the inner magnetosphere which is similar to those of the warm plasma cloak and the oxygen torus. We therefore conclude that FALEO is a source of those cold ion populations.

Background: Limited information is available about patterns of surgical management of early breast cancer by ethnicity of women in England, and any potential inequalities in the treatment received for breast cancer. Methods: National Cancer Registration and Analysis Service (NCRAS) data for 164 143 women diagnosed with early invasive breast cancer (ICD-10 C50) during 2012-2017 was analysed. Multivariable logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the risk of mastectomy versus breast conserving surgery by ethnicity (Black African, Black Caribbean, Indian, Pakistani, White), adjusting for age, region, deprivation, year of diagnosis, comorbidity and stage at diagnosis. Results: The proportion of women undergoing mastectomy fell by ~5% during 2012 to 2017 across all the ethnic groups examined. In unadjusted analyses, each ethnic minority group had a significantly higher odds of mastectomy compared to White women; however in the fully adjusted model, there were no significantly increased odds for mastectomy for women of any ethnic minority groups examined. For example, compared to White women, the unadjusted and fully adjusted OR (95% confidence interval) for mastectomy was 1.14 (1.05-1.20) and 1.04 (0.96-1.14) for Indian women, and 1.45 (1.30-1.62) and 1.00 (0.89-1.13) for Black African women. This attenuation in the odds ratios by ethnicity was largely due to adjustment for age and stage. Conclusions: Allowing for different patterns of age and stage at presentation, the surgical management of early breast cancer is similar in all women, regardless of ethnicity.

About 1 in 10 postmenopausal UK women are currently prescribed oral bisphosphonates, but there are concerns about their adverse effects. Osteonecrosis of the jaw is a recognised uncommon but important side effect of intravenous bisphosphonates, but epidemiological evidence on risk of osteonecrosis of the jaw associated with oral bisphosphonate use is less conclusive. The incidence of hospital admission with osteonecrosis of the jaw was examined among 521,695 Million Women Study participants, aged 64.7 years at baseline. Cox proportional hazards regression was used to estimate adjusted relative risks (RRs) and 95% confidence intervals (CIs) associated with use of oral bisphosphonates in postmenopausal women followed-up by record-linkage to National Health Service hospital admission databases. During mean follow-up of 8.2 years per woman, 100 women were admitted to hospital with first recorded osteonecrosis of the jaw, at mean age 72.4 years. Almost a third (29/100) of the cases had ever-used oral bisphosphonates. Ever-users had a six-fold increased risk of hospital admission for osteonecrosis of the jaw, when compared with never-users (adjusted RR = 6.09, 95% CI 3.83-9.66; p 0.0001). The relative risk for osteonecrosis of the jaw in never-users of oral bisphosphonates was increased in women with prior cancer (RR = 3.40, 2.22-5.22, p 0.0001). The estimated absolute risk of hospital admission for osteonecrosis of the jaw over a 5-year period from age 70 to 74 in women without prior cancer was 0.09 per 1000 in never-users and 0.69 per 1000 in ever-users of oral bisphosphonates. In this UK population of postmenopausal women, use of oral bisphosphonates was associated with a 6-fold increased risk of hospital admission with osteonecrosis of the jaw, accounting for around one-third of cases, with an excess risk of about 0.6/1000 users over 5 years.

OBJECTIVES:Previous studies of the association between physical activity and adiposity are largely based on physical activity and body mass index (BMI) from questionnaires, which are prone to inaccurate and biased reporting. We assessed the associations of accelerometer-measured and questionnaire-measured physical activity with BMI, waist circumference and body fat per cent measured by bioelectrical impedance and dual-energy X-ray absorptiometry (DXA). DESIGN:Cross-sectional analysis of UK Biobank participants. SETTING:UK Biobank assessment centres. PARTICIPANTS:78 947 UK Biobank participants (35 955 men and 42 992 women) aged 40-70 at recruitment, who had physical activity measured by both questionnaire and accelerometer. MAIN OUTCOME MEASURES:BMI, waist circumference and body fat per cent measured by bioelectrical impedance. RESULTS:Greater physical activity was associated with lower adiposity. Women in the top 10th of accelerometer-measured physical activity had a 4.8 (95% CI 4.6 to 5.0) kg/m2 lower BMI, 8.1% (95% CI 7.8% to 8.3%) lower body fat per cent and 11.9 (95% CI 11.4 to 12.4) cm lower waist circumference. Women in the top 10th of questionnaire-measured physical activity had a 2.5 (95% CI 2.3 to 2.7) kg/m2 lower BMI, 4.3% (95% CI 4.0% to 4.5%) lower body fat per cent and 6.4 (95% CI 5.9 to 6.9) cm lower waist circumference, compared with women in the bottom 10th. The patterns were similar in men and also similar to body fat per cent measured by DXA compared with impedance. CONCLUSION:Our findings of approximately twofold stronger associations between physical activity and adiposity with objectively measured than with self-reported physical activity emphasise the need to incorporate objective measures in future studies.

Background:Available evidence on diet and glioma risk comes mainly from studies with retrospective collection of dietary data. To minimise possible differential dietary recall between those with and without glioma, we present findings from three large prospective studies. Methods:Participants included 692,176 from (UK) Million Women Study, 470,780 from (US) NIH-AARP Study, and 99,148 from (US) PLCO Study. Cox regression yielded study-specific adjusted relative risks for glioma in relation to 15 food groups, 14 nutrients, and 3 dietary patterns, which were combined, weighted by inverse-variances of the relative risks. Separate analyses by

Background In 2006, the Bowel Cancer Screening Programme (BCSP) in England began offering biennial faecal occult blood testing (FOBt) at ages 60–69 years. Although FOBt is aimed at detecting colorectal neoplasms, other conditions can affect the result. In a large UK prospective study, we examined associations, both before and after screening, between FOBt positivity and 10 conditions that are often associated with gastrointestinal bleeding. Methods By electronically linking BCSP and Million Women Study records, we identified 604 495 women without previous colorectal cancer who participated in their first routine FOBt screening between 2006 and 2012. Regression models, using linked national hospital admission records, yielded adjusted relative risks (RRs) in FOBt-positive versus FOBt-negative women for colorectal cancer, adenoma, diverticular disease, inflammatory bowel disease, haemorrhoids, upper gastrointestinal cancer, oesophagitis, peptic ulcer, anaemia and other haematological disorders. Results RRs in FOBt-positive versus FOBt-negative women were 201.3 (95% CI 173.8–233.2) for colorectal cancer and 197.9 (95% CI 180.6–216.8) for adenoma within 12 months after screening and 3.49 (95% CI 2.31–5.26) and 4.88 (95% CI 3.80–6.26), respectively, 12–24 months after screening; P

Faecal occult blood (FOB) ‐ based screening programmes for colorectal cancer detect about half of all cancers. Little is known about individual health behavioural characteristics which may be associated with screen‐detected and interval cancers. Electronic linkage between the UK National Health Service Bowel Cancer Screening Programme (BCSP) in England, cancer registration and other national health records, and a large on‐going UK cohort, the Million Women Study, provided data on 628,976 women screened using a guaiac‐FOB test (gFOBt) between 2006 and 2012. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated by logistic and Cox regression for associations between individual lifestyle factors and risk of colorectal tumours. Among screened women, 766 were diagnosed with screen‐detected colorectal cancer registered within 2 years after a positive gFOBt result, and 749 with interval colorectal cancers registered within 2 years after a negative gFOBt result. Current smoking was significantly associated with risk of interval cancer (RR 1.64, 95%CI 1.35–1.99) but not with risk of screen‐detected cancer (RR 1.03, 0.84–1.28), and was the only factor of eight examined to show a significant difference in risk between interval and screen‐detected cancers (p for difference, 0.003). Compared to screen‐detected cancers, interval cancers tended to be sited in the proximal colon or rectum, to be of non‐adenocarcinoma morphology, and to be of higher stage.

Electromagnetic ion cyclotron (EMIC) waves can drive precipitation of tens of keV protons and relativistic electrons, and are a potential candidate for causing radiation belt flux dropouts. In this study, we quantitatively analyze three cases of EMIC‐driven precipitation, which occurred near the dusk sector observed by multiple Low‐Earth‐Orbiting (LEO) Polar Operational Environmental Satellites/Meteorological Operational satellite programme (POES/MetOp) satellites. During EMIC wave activity, the proton precipitation occurred from few tens of keV up to hundreds of keV, while the electron precipitation was mainly at relativistic energies. We compare observations of electron precipitation with calculations using quasi‐linear theory. For all cases, we consider the effects of other magnetospheric waves observed simultaneously with EMIC waves, namely, plasmaspheric hiss and magnetosonic waves, and find that the electron precipitation at MeV energies was predominantly caused by EMIC‐driven pitch angle scattering. Interestingly, each precipitation event observed by a LEO satellite extended over a limited L shell region (ΔL ~ 0.3 on average), suggesting that the pitch angle scattering caused by EMIC waves occurs only when favorable conditions are met, likely in a localized region. Furthermore, we take advantage of the LEO constellation to explore the occurrence of precipitation at different L shells and magnetic local time sectors, simultaneously with EMIC wave observations near the equator (detected by Van Allen Probes) or at the ground (measured by magnetometers). Our analysis shows that although EMIC waves drove precipitation only in a narrow ΔL, electron precipitation was triggered at various locations as identified by POES/MetOp over a rather broad region (up to ~4.4 hr MLT and ~1.4 L shells) with similar patterns between satellites.

The evolution of the radiation belts in L-shell (L), energy (E), and equatorial pitch angle (alpha(0)) is analyzed during the calm 11-day interval (4-15 March) following the 1 March 2013 storm. Magnetic Electron and Ion Spectrometer (MagEIS) observations from Van Allen Probes are interpreted alongside 1D and 3D Fokker-Planck simulations combined with consistent event-driven scattering modeling from whistler mode hiss waves. Three (L, E, alpha(0)) regions persist through 11 days of hiss wave scattering; the pitch angle-dependent inner belt core (L similar to similar to 5 and E similar to < 100 keV), and a distinct pocket of electrons (L similar to [4.5, 5.5] and E similar to [0.7, 2] MeV). The pitch angle homogeneous outer belt is explained by the diffusion coefficients that are roughly constant for alpha(0) similar to 100 keV, 3.5 < L < L-pp similar to 6. Thus, observed unidirectional flux decays can be used to estimate local pitch angle diffusion rates in that region. Top-hat distributions are computed and observed at L similar to 3-3.5 and E = 100-300 keV.

Introduction Published findings on the associations between smoking and the incidence of cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are inconsistent. We aimed to generate prospective evidence on these relationships, overall and by anatomical site. Methods We followed 1,223,626 women without prior cancer by electronic linkage to national cancer registration data. Questionnaire information about smoking and other factors was recorded at recruitment (1996-2001) and every 3-5 years subsequently. Cox regression yielded adjusted relative risks (RRs) comparing smokers versus never-smokers. Results After 14 (SD4) years follow-up per woman, 6699 had a first registered cutaneous SCC and 48,666 a first BCC. In current versus never-smokers, SCC incidence was increased (RR=1.22, 95%CI 1.15-1.31) but BCC incidence was decreased (RR=0.80, 0.78-0.82). RRs varied substantially by anatomical site; for the limbs, current smoking was associated with an increased incidence of SCC (1.55, 1.41-1.71) and a decreased incidence of BCC (0.72, 0.66-0.79), but for facial lesions there was little association of current smoking with either SCC (0.93, 0.82-1.06) or BCC (0.92, 0.88-0.96). Findings in meta-analyses of results from this and 7 other prospective studies were largely dominated by the findings in this study. Conclusion Smoking-associated risks for cutaneous SCC and BCC are opposite to each other, and may vary by anatomical site.

Body size is an important modifiable risk factor for postmenopausal breast cancer. However, it remains unclear whether direct measures of fat mass are better indicators of risk than anthropometric measures, or whether central adiposity may contribute to risk beyond overall adiposity. We analyzed data from 162,691 postmenopausal women in UK Biobank followed from 2006 to 2014. Body size was measured by trained technicians. Multivariable‐adjusted Cox regression was used to estimate relative risks. Analyses were stratified by age at recruitment, region and socioeconomic status, and adjusted for family history of breast cancer, age at menarche, age at first birth, parity, age at menopause, previous hormone replacement therapy use, smoking, alcohol intake, height, physical activity and ethnicity. We observed 2,913 incident invasive breast cancers during a mean 5.7 years of follow‐up. There was a continuous increase in risk of postmenopausal breast cancer with increasing adiposity, across all measures. The point estimate, comparing women in the top (median 37.6 kg) to bottom (median 17.6 kg) quartile of body fat mass was 1.70 (95% confidence interval 1.52–1.90). The magnitudes of the associations between per SD increase in BMI and body fat mass with breast cancer risk were similar, suggesting impedance measures of fat were not substantially better indicators of risk than anthropometric measures. After adjusting for body fat mass, the associations between anthropometric measures of central adiposity and breast cancer risk were attenuated. The magnitude of risk, across all measures of adiposity, was greater in women who had been postmenopausal for 12 or more years.

We perform a statistical study calculating electromagnetic ion cyclotron (EMIC) wave amplitudes based off in situ plasma measurements taken by the Van Allen Probes’ (1.1–5.8 Re) Helium, Oxygen, Proton, Electron (HOPE) instrument. Calculated wave amplitudes are compared to EMIC waves observed by the Electric and Magnetic Field Instrument Suite and Integrated Science on board the Van Allen Probes during the same period. The survey covers a 22-month period (1 November 2012 to 31 August 2014), a full Van Allen Probe magnetic local time (MLT) precession. The linear theory proxy was used to identify EMIC wave events with plasma conditions favorable for EMIC wave excitation. Two hundred and thirty-two EMIC wave events (103 H+-band and 129 He+-band) were selected for this comparison. Nearly all events selected are observed beyond L = 4. Results show that calculated wave amplitudes exclusively using the in situ HOPE measurements produce amplitudes too low compared to the observed EMIC wave amplitudes. Hot proton anisotropy (Ahp) distributions are asymmetric in MLT within the inner (L

Objective: To compare associations of behavioural and related factors for incident subarachnoid and intracerebral haemorrhage and ischaemic stroke. Methods: 712,433 Million Women Study participants without prior stroke, heart disease or cancer reported behavioural and related factors at baseline (1999-2007) and were followed by record linkage to national hospital admission and death databases. Cox regression yielded adjusted relative risks (RRs) by type of stroke. Heterogeneity was assessed using chi-squared tests. Where appropriate, meta-analyses were done of published prospective studies. Results: After 12.9 (SD 2.6) years follow-up, 8128 women had an incident ischaemic stroke, 2032 intracerebral haemorrhage and 1536 subarachnoid haemorrhage. In women with diabetes, risk of ischaemic stroke was substantially increased (RR=2.01; 95% CI 1.84-2.20), intracerebral haemorrhage slightly increased (RR=1.31; 1.04-1.65) but subarachnoid haemorrhage reduced (RR=0.43; 0.26-0.69) (heterogeneity by stroke type, pConclusions: Classic risk factors for stroke have considerably different effects on the three main pathological types of stroke.

BACKGROUND: Oral contraceptives are known to reduce the incidence rate of endometrial cancer, but it is uncertain how long this effect lasts after use ceases, or whether it is modified by other factors.METHODS: Individual participant datasets were sought from principal investigators and provided centrally for 27 276 women with endometrial cancer (cases) and 115 743 without endometrial cancer (controls) from 36 epidemiological studies. The relative risks (RRs) of endometrial cancer associated with oral contraceptive use were estimated using logistic regression, stratified by study, age, parity, body-mass index, smoking, and use of menopausal hormone therapy.FINDINGS: The median age of cases was 63 years (IQR 57-68) and the median year of cancer diagnosis was 2001 (IQR 1994-2005). 9459 (35%) of 27 276 cases and 45 625 (39%) of 115 743 controls had ever used oral contraceptives, for median durations of 3·0 years (IQR 1-7) and 4·4 years (IQR 2-9), respectively. The longer that women had used oral contraceptives, the greater the reduction in risk of endometrial cancer; every 5 years of use was associated with a risk ratio of 0·76 (95% CI 0·73-0·78; p

Background There is limited information about participation in organised population-wide screening programmes by people with disabilities. Methods Data from the National Health Service routine screening programmes in England were linked to information on disability reported by Million Women Study cohort participants. Results Of 473,185 women offered routine breast or bowel cancer screening, 23% reported some disability. Women with disabilities were less likely than other women to participate in breast cancer screening (RR=0.64, 95% CI: 0.62-0.65) and in bowel cancer screening (RR=0.75, 0.73-0.76). Difficulties with self-care or vision were associated with the greatest reduction in screening participation. Conclusion Participation in routine cancer screening programmes in England is reduced in people with disabilities and participation varies by type of disability.

Hatching rates and the timing of diapause termination are traits of high relevance in ecology and evolution of diapausing organisms. The analysis of hatching from dormant stages of planktonic organisms is an active area of research, which has been extensively studied in the context of phenology adjustment over latitude. Research on populations from temporary ponds has revealed temporal hatching profiles consisting of various hatching peaks, which is considered a risk-spreading strategy. Studies on outstanding scientific questions such as the evolution of risk-spreading strategies, the importance of genetic variation in hatching in an eco-evolutionary context, and the genomic underpinning of hatching phenotypes all require very large sample sizes. We therefore developed a high throughput approach for the assessment of hatching rates and temporal hatching profiles of resting stages from crustacean zooplankton. Our method consists in the photographic monitoring of resting stages hatching assays and the detection of hatchlings using free software for the automation of biological image analysis. We compared the performance of our new method with data obtained by traditional visual assessment of hatching. Our results indicate that our approach is highly accurate (>95) and raises efficiency by a factor of 10 compared to non-automated visual assessment. Our new high throughput approach therefore allows to upscale the analysis of temporal hatching profiles and hatching success to sample sizes that will enable large-scale genomic studies or massive phenotyping and monitoring of these highly relevant traits in the future.

Background: Overweight and obesity are increasing worldwide. To help assess their relevance to mortality in different populations we conducted individual-participant-data meta-analyses of the prospective studies of body mass index (BMI), limiting confounding and reverse causality by restricting analyses to never-smokers and excluding prior disease and the first 5 years of follow- up. Methods: Of 10,625,411 participants in Asia, Australia/New Zealand, Europe, and North America from 239 prospective studies (median follow-up 13·7 [IQR: 11·4-14·7] years), 3,951,455 in 189 studies were never-smokers without specific chronic diseases at recruitment who survived 5 years, of whom 385,879 died. The primary analyses are of these deaths, using age and sex-adjusted hazard ratios (HRs). Findings: All-cause mortality was minimal (HR=1) at BMI (kg/m2) 20-25, and increased significantly both just below this range (BMI 18·5-25, mortality increased approximately log-linearly with BMI; HR per 5 units higher BMI was 1·31 (1·29-1·33) in all regions; 1·39 (1·35-1·43) in Europe; 1·29 (1·26-1·32) in North America, 1·39 (1·34-1·44) in East Asia, and 1.31 (1.27, 1.35) in Australia/New Zealand. This HR per 5 units higher BMI (for BMI>25) was greater in younger than older people (1.52 at 35–49 years vs 1·21 at 70-89 years; PheterogeneityInterpretation: The associations of both overweight and obesity with higher all-cause mortality were broadly consistent in four continents. This supports strategies to combat the entire spectrum of excess adiposity in many populations.

BACKGROUND: Smoking has been linked to mucinous ovarian cancer, but its effects on other ovarian cancer subtypes and on overall ovarian cancer risk are unclear, and the findings from most studies with relevant data are unpublished. To assess these associations, we review the published and unpublished evidence. METHODS: Eligible epidemiological studies were identified by electronic searches, review articles, and discussions with colleagues. Individual participant data for 28,114 women with and 94,942 without ovarian cancer from 51 epidemiological studies were analysed centrally, yielding adjusted relative risks (RRs) of ovarian cancer in smokers compared with never smokers. FINDINGS: After exclusion of studies with hospital controls, in which smoking could have affected recruitment, overall ovarian cancer incidence was only slightly increased in current smokers compared with women who had never smoked (RR 1·06, 95% CI 1·01-1·11, p=0·01). Of 17,641 epithelial cancers with specified histology, 2314 (13%) were mucinous, 2360 (13%) endometrioid, 969 (5%) clear-cell, and 9086 (52%) serous. Smoking-related risks varied substantially across these subtypes (p(heterogeneity)

INTRODUCTION: Epidemiological studies rely on data supplied by central cancer registration sources to be timely, accurate and complete. Validation studies of such data at a national level are limited. Data collected for the Million Women Study was used to compare the level of agreement between the Office for National Statistics (ONS) and the National Health Service Breast Screening Programme (NHSBSP) in the recording of incident screen-detected breast cancer histology between 1996 and 2001. METHODS: 1.3 million women aged 50 to 64 years were recruited into the Million Women Study cohort via the NHSBSP. Incident screen-detected breast cancer histologies were notified separately by the ONS and NHSBSP. ICD-10 and ICD-02 ONS codes and NHSBSP histology data were similarly coded to allow for comparison in terms of cancer invasiveness and morphology. The statistical outcome measures are percentage agreement and the kappa statistic. RESULTS: A total of 5,886 incident screen-detected breast cancers were available for analysis. Of the 5,886 screen-detected cancers reported by the ONS and NHSBSP, 5,684 (96.6%, kappa = 0.9) agreed in terms of the degree of invasiveness. Of the 5,458 cancers that had been assigned a specific morphology code, there was exact agreement between the ONS and the NHSBSP in 4,922 cases (90.2%, kappa = 0.8). CONCLUSION: There is an excellent level of agreement between the ONS and NHSBSP in the recording of the histology of screen-detected breast cancer. From these results it is not possible to comment on which source of data is the more or less accurate, although the differences are very small.

OBJECTIVE: To evaluate the extent to which 'high-risk' sexual behaviour is influenced by awareness of partners' HIV status among gay men. DESIGN: Structured interviews and collection of saliva samples for anonymous linked testing for HIV-1 antibodies. SETTING: Genitourinary medicine clinics and the gay community. SUBJECTS: Men (n = 677) who reported sexual contact with another man in the last 5 years. RESULTS: The majority of respondents (63%) had had an HIV-antibody test. Analysis of data showed that in 15% of the respondents' 1380 partnerships, HIV status was known by both parties. However, the majority of partnerships involved only safe sex. Only 26% of the partnerships in which unprotected penetrative anal sex had occurred involved mutual knowledge of HIV status and was most likely to occur with regular rather than non-regular/causal partners. Logistic regression revealed that this latter association could not be explained in terms of mutual HIV status knowledge. CONCLUSIONS: Despite widespread HIV testing, the majority of gay men engaging in high-risk sex are unaware of their partner's HIV status.

Objective: To determine whether transdermal compared with oral use of hormone replacement therapy reduces the risk of gallbladder disease in postmenopausal women. Design: Prospective cohort study (Million Women Study). Setting: Women registered with the National Health Service (NHS) in England and Scotland. Participants: 1 001 391 postmenopausal women (mean age 56) recruited between 1996 and 2001 from NHS breast screening centres and followed by record linkage to routinely collected NHS hospital admission data for gallbladder disease. Main outcome measures: Adjusted relative risk and standardised incidence rates of hospital admission for gallbladder disease or cholecystectomy according to use of hormone replacement therapy. Results: During follow-up 19 889 women were admitted for gallbladder disease; 17 190 (86%) had a cholecystectomy. Compared with never users of hormone replacement therapy, current users were more likely to be admitted for gallbladder disease (relative risk 1.64, 95% confidence interval 1.58 to 1.69) but risks were substantially lower with transdermal therapy than with oral therapy (relative risk 1.17, 1.10 to 1.24 v 1.74, 1.68 to 1.80; heterogeneity P0.625 mg, 1.91 (1.78 to 2.04) v ≤0.625 mg, 1.76 (1.68 to 1.84); heterogeneity P=0.02; estradiol >1 mg, 1.68 (1.59 to 1.77) v

Objective: To identify risk factors for cataracts treated surgically in post-menopausal women. Design: Population-based, prospective cohort study. Participants: A total of 1,312,051 post-menopausal women in the UK Million Women Study, aged 56 years on average (SD 4.8), without previous cataract surgery, hospital admission with cataracts or cancer at baseline, were followed for cataracts treated surgically. Methods: Cox regression was used to calculate adjusted relative risks (RRs) for cataract surgery by lifestyle factors, treatment for diabetes, reproductive history and use of hormonal therapies. Main outcome measures: Cataract surgery identified by linkage to central National Health Service records for in-patient and day-patient admissions (Hospital Episode Statistics for England and Scottish Morbidity Records in Scotland). Results: Overall, 89,343 women underwent cataract surgery during an average of 11 (SD 3) years of follow-up. Women with diabetes were at greatest risk (diabetes vs no diabetes RR = 2.90, 95% CI 2.82-2.97). Other factors associated with an increased risk of cataract surgery were: current smoking (current smokers of >=15 cigarettes/day vs never smokers RR = 1.26, 95% CI 1.23-1.30) and obesity (BMI >=30 vs Conclusions: Diabetes, smoking and obesity were risk factors for cataract surgery. Alcohol use, physical activity, reproductive history and use of hormonal therapies had little, if any, association with cataract surgery risk.

Histopathological and molecular studies suggest that different histological subtypes (histotypes) of ovarian cancer have different aetiologies. Few studies have been large enough to explore reliably the effect of tubal ligation (sterilization), which has been associated with a reduced overall risk of ovarian cancer, on different tumour histotypes. In a prospective study of 1.1 million UK women without prior cancer or bilateral oophorectomy, 8,035 ovarian cancers occurred during mean follow‐up of 13.8 years. Using a Cox proportional hazards model, we estimated adjusted relative risks of ovarian cancer associated with tubal ligation. Overall, there was substantial heterogeneity in tumour risk associated with tubal ligation for the four main histotypes, serous, endometrioid, mucinous and clear cell (heterogeneity: p

BACKGROUND: Postmenopausal women who use hormone-replacement therapy (HRT) containing oestrogen alone are at increased risk of endometrial cancer. To minimise this risk, many HRT users who have not had a hysterectomy use combined oestrogen-progestagen preparations or tibolone. Limited information is available on the incidence of endometrial cancer in users of these therapies. METHODS: 716,738 postmenopausal women in the UK without previous cancer or previous hysterectomy were recruited into the Million Women Study in 1996-2001, provided information about their use of HRT and other personal details, and were followed up for an average of 3.4 years, during which time 1320 incident endometrial cancers were diagnosed. FINDINGS: 320,953 women (45%) reported at recruitment that they had used HRT, among whom 69,577 (22%) last used continuous combined therapy (progestagen added daily to oestrogen), 145,486 (45%) last used cyclic combined therapy (progestagen added to oestrogen, usually for 10-14 days per month), 28,028 (9%) last used tibolone, and 14,204 (4%) last used oestrogen-only HRT. These HRT types had sharply contrasting effects on the overall risk of endometrial cancer (p

Background: Overweight and obesity are increasing worldwide. To help assess their relevance to mortality in different populations we conducted individual-participant-data meta-analyses of the prospective studies of body mass index (BMI), limiting confounding and reverse causality by restricting analyses to never-smokers and excluding prior disease and the first 5 years of follow- up. Methods: Of 10,625,411 participants in Asia, Australia/New Zealand, Europe, and North America from 239 prospective studies (median follow-up 13·7 [IQR: 11·4-14·7] years), 3,951,455 in 189 studies were never-smokers without specific chronic diseases at recruitment who survived 5 years, of whom 385,879 died. The primary analyses are of these deaths, using age and sex-adjusted hazard ratios (HRs). Findings: All-cause mortality was minimal (HR=1) at BMI (kg/m2) 20-25, and increased significantly both just below this range (BMI 18·5-25, mortality increased approximately log-linearly with BMI; HR per 5 units higher BMI was 1·31 (1·29-1·33) in all regions; 1·39 (1·35-1·43) in Europe; 1·29 (1·26-1·32) in North America, 1·39 (1·34-1·44) in East Asia, and 1.31 (1.27, 1.35) in Australia/New Zealand. This HR per 5 units higher BMI (for BMI>25) was greater in younger than older people (1.52 at 35–49 years vs 1·21 at 70-89 years; PheterogeneityInterpretation: The associations of both overweight and obesity with higher all-cause mortality were broadly consistent in four continents. This supports strategies to combat the entire spectrum of excess adiposity in many populations.

Background Many studies investigating long-term vascular disease risk associated with hypertensive pregnancies examined risks in relatively young women among whom vascular disease is uncommon. We examined the prospective relation between a history of hypertension during pregnancy and coronary heart disease (CHD) and stroke in middle-aged UK women. Methods In 1996–2001, 1.1 million parous women (mean age = 56 years) without vascular disease at baseline reported their history of hypertension during pregnancy and other factors. They were followed for incident CHD and stroke (hospitalisation or death). Adjusted relative risks (RRs) were calculated using Cox regression. Results Twenty-six percent (290,008/1.1 million) reported having had a hypertensive pregnancy; 27% (79,163/290,008) of women with hypertensive pregnancy, but only 10% (82,145/815,560) of those without hypertensive pregnancy, reported being treated for hypertension at baseline. Mean follow-up was 11.6 years (mean ages at diagnosis/N of events: CHD = 65 years/N = 68,161, ischaemic stroke = 67 years/N = 8365, haemorrhagic stroke = 64 years/N = 5702). Overall, the RRs (95% confidence interval [CI]) of incident disease in women with hypertensive pregnancy versus those without such history were: CHD = 1.29 (1.27–1.31), ischaemic stroke = 1.29 (1.23–1.35), and haemorrhagic stroke = 1.14 (1.07–1.21). However, among women with hypertensive pregnancy who were not taking hypertension treatment at baseline, their RRs (95% CI) were only modestly increased: CHD = 1.17 (1.14–1.19), ischaemic stroke = 1.18 (1.11–1.25), and haemorrhagic stroke = 1.09 (1.02–1.18). Conclusion Hypertension during pregnancy was associated with increased CHD and stroke incidence in middle age, largely because such women also had hypertension in their 50s and 60s, which has a substantially greater effect on vascular disease risk than hypertension during pregnancy without hypertension later in life.

Background: Anal cancer incidence increases with age and is higher in women than men. Risk factors in this group other than high-risk human papillomavirus infection are unclear. Methods: In all, 1.3 million women were recruited in 1996–2001 and followed for incident anal cancer. Cox regression models were used to calculate relative risks (RRs) for anal cancer by various potential risk factors. Results: Five hundred and seventeen incident anal cancers were registered over 13 years of follow-up. The largest RR was associated with a history of cervical intraepithelial neoplasia grade 3 (CIN 3; RR=4.03, 95% CI 2.59–6.28). Other factors associated with significantly increased risks in multivariate analyses were: ever smoking (RR=1.49, 1.24–1.80); previous use of oral contraceptives (RR=1.51, 1.24–1.83); nulliparity (RR=1.61, 1.24–2.07); tubal ligation (RR=1.39, 1.13–1.70) and not living with a partner (RR=1.82, 1.40–2.38). The association with smoking was significantly greater for squamous cell carcinoma than adenocarcinoma of the anus (RR 1.66 vs 0.89, P for heterogeneity=0.04). Conclusions: History of CIN 3, smoking, past oral contraceptive use, nulliparity, tubal ligation and not living with a partner are risk factors for anal cancer in women. There was a significant increase in risk associated with smoking for squamous cell anal cancers but not adenocarcinomas.

Updated online 26 May 2016: This article was originally published [10.1038/bjc.2015.89] under a CC BY-NC-SA 4.0 license, but has now been made available under a CC BY 4.0 license [10.1038/bjc.2016.13]. The PDF and HTML versions of the paper have been modified accordingly.

Histopathological and molecular studies suggest that different histological subtypes (histotypes) of ovarian cancer have different aetiologies. Few studies have been large enough to explore reliably the effect of tubal ligation (sterilization), which has been associated with a reduced overall risk of ovarian cancer, on different tumour histotypes. In a prospective study of 1.1 million UK women without prior cancer or bilateral oophorectomy, 8,035 ovarian cancers occurred during mean follow-up of 13.8 years. Using a Cox proportional hazards model, we estimated adjusted relative risks of ovarian cancer associated with tubal ligation. Overall, there was substantial heterogeneity in tumour risk associated with tubal ligation for the four main histotypes, serous, endometrioid, mucinous and clear cell (heterogeneity: p