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1.
  • Gapstur, S. M., et al. (author)
  • Menopausal hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological studies
  • 2015
  • In: The Lancet. - 1474-547X. ; 385:9980, s. 1835-1842
  • Journal article (peer-reviewed)abstract
    • Background Half the epidemiological studies with information about menopausal hormone therapy and ovarian cancer risk remain unpublished, and some retrospective studies could have been biased by selective participation or recall. We aimed to assess with minimal bias the effects of hormone therapy on ovarian cancer risk. Methods Individual participant datasets from 52 epidemiological studies were analysed centrally. The principal analyses involved the prospective studies (with last hormone therapy use extrapolated forwards for up to 4 years). Sensitivity analyses included the retrospective studies. Adjusted Poisson regressions yielded relative risks (RRs) versus never-use. Findings During prospective follow-up, 12 110 postmenopausal women, 55% (6601) of whom had used hormone therapy, developed ovarian cancer. Among women last recorded as current users, risk was increased even with <5 years of use (RR 1.43, 95% CI 1.31-1.56; p<0.0001). Combining current-or-recent use (any duration, but stopped <5 years before diagnosis) resulted in an RR of 1.37 (95% CI 1.29-1.46; p<0.0001); this risk was similar in European and American prospective studies and for oestrogen-only and oestrogen-progestagen preparations, but differed across the four main tumour types (heterogeneity p<0.0001), being definitely increased only for the two most common types, serous (RR 1.53, 95% CI 1.40-1.66; p<0.0001) and endometrioid (1.42, 1.20-1.67; p<0.0001). Risk declined the longer ago use had ceased, although about 10 years after stopping long-duration hormone therapy use there was still an excess of serous or endometrioid tumours (RR 1.25, 95% CI 1.07-1.46, p=0.005). Interpretation The increased risk may well be largely or wholly causal; if it is, women who use hormone therapy for 5 years from around age 50 years have about one extra ovarian cancer per 1000 users and, if its prognosis is typical, about one extra ovarian cancer death per 1700 users.
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2.
  • Beral, V., et al. (author)
  • Ovarian cancer and smoking: individual participant meta-analysis including 28 114 women with ovarian cancer from 51 epidemiological studies
  • 2012
  • In: The Lancet Oncology. - 1474-5488. ; 13:9, s. 946-956
  • Journal article (peer-reviewed)abstract
    • 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)<0.0001). For mucinous cancers, incidence was increased in current versus never smokers (1.79, 95% CI 1.60-2.00, p<0.0001), but the increase was mainly in borderline malignant rather than in fully malignant tumours (2.25, 95% CI 1.91-2.65 vs 1.49, 1.28-1.73; p(heterogeneity)=0.01; almost half the mucinous tumours were only borderline malignant). Both endometrioid (0.81, 95% CI 0.72-0.92, p=0.001) and clear-cell ovarian cancer risks (0.80, 95% CI 0.65-0.97, p=0.03) were reduced in current smokers, and there was no significant association for serous ovarian cancers (0.99, 95% CI 0.93-1.06, p=0.8). These associations did not vary significantly by 13 sociodemographic and personal characteristics of women including their body-mass index, parity, and use of alcohol, oral contraceptives, and menopausal hormone therapy. Interpretation The excess of mucinous ovarian cancers in smokers, which is mainly of tumours of borderline malignancy, is roughly counterbalanced by the deficit of endometrioid and clear-cell ovarian cancers. The substantial variation in smoking-related risks by tumour subtype is important for understanding ovarian carcinogenesis.
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3.
  • Beral, V., et al. (author)
  • Ovarian Cancer and Body Size : Individual Participant Meta-Analysis Including 25,157 Women with Ovarian Cancer from 47 Epidemiological Studies
  • 2012
  • In: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 9:4
  • Journal article (peer-reviewed)abstract
    • Background: Only about half the studies that have collected information on the relevance of women's height and body mass index to their risk of developing ovarian cancer have published their results, and findings are inconsistent. Here, we bring together the worldwide evidence, published and unpublished, and describe these relationships. Methods and Findings: Individual data on 25,157 women with ovarian cancer and 81,311 women without ovarian cancer from 47 epidemiological studies were collected, checked, and analysed centrally. Adjusted relative risks of ovarian cancer were calculated, by height and by body mass index. Ovarian cancer risk increased significantly with height and with body mass index, except in studies using hospital controls. For other study designs, the relative risk of ovarian cancer per 5 cm increase in height was 1.07 (95% confidence interval [CI], 1.05-1.09; p<0.001); this relationship did not vary significantly by women's age, year of birth, education, age at menarche, parity, menopausal status, smoking, alcohol consumption, having had a hysterectomy, having first degree relatives with ovarian or breast cancer, use of oral contraceptives, or use of menopausal hormone therapy. For body mass index, there was significant heterogeneity (p<0.001) in the findings between ever-users and never-users of menopausal hormone therapy, but not by the 11 other factors listed above. The relative risk for ovarian cancer per 5 kg/m(2) increase in body mass index was 1.10 (95% CI, 1.07-1.13; p<0.001) in never-users and 0.95 (95% CI, 0.92-0.99; p = 0.02) in ever-users of hormone therapy. Conclusions: Ovarian cancer is associated with height and, among never-users of hormone therapy, with body mass index. In high-income countries, both height and body mass index have been increasing in birth cohorts now developing the disease. If all other relevant factors had remained constant, then these increases in height and weight would be associated with a 3% increase in ovarian cancer incidence per decade.
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4.
  • Wade, C. M., et al. (author)
  • Genome Sequence, Comparative Analysis, and Population Genetics of the Domestic Horse
  • 2009
  • In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 326:5954, s. 865-867
  • Journal article (peer-reviewed)abstract
    • We report a high-quality draft sequence of the genome of the horse ( Equus caballus). The genome is relatively repetitive but has little segmental duplication. Chromosomes appear to have undergone few historical rearrangements: 53% of equine chromosomes show conserved synteny to a single human chromosome. Equine chromosome 11 is shown to have an evolutionary new centromere devoid of centromeric satellite DNA, suggesting that centromeric function may arise before satellite repeat accumulation. Linkage disequilibrium, showing the influences of early domestication of large herds of female horses, is intermediate in length between dog and human, and there is long-range haplotype sharing among breeds.
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5.
  • Barwick, S. W., et al. (author)
  • A first search for cosmogenic neutrinos with the ARIANNA Hexagonal Radio Array
  • 2015
  • In: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 70, s. 12-26
  • Journal article (peer-reviewed)abstract
    • The ARIANNA experiment seeks to observe the diffuse flux of neutrinos in the 10(8)-10(10) GeV energy range using a grid of radio detectors at the surface of the Ross Ice Shelf of Antarctica. The detector measures the coherent Cherenkov radiation produced at radio frequencies, from about 100 MHz-1 GHz, by charged particle showers generated by neutrino interactions in the ice. The ARIANNA Hexagonal Radio Array (HRA) is being constructed as a prototype for the full array. During the 2013-14 austral summer, three HRA stations collected radio data which was wirelessly transmitted off site in nearly real-time. The performance of these stations is described and a simple analysis to search for neutrino signals is presented. The analysis employs a set of three cuts that reject background triggers while preserving 90% of simulated cosmogenic neutrino triggers. No neutrino candidates are found in the data and a model-independent 90% confidence level Neyman upper limit is placed on the all flavor nu + (nu) over bar flux in a sliding decade-wide energy bin. The limit reaches a minimum of 1.9 x 10(-23) GeV-1 cm(-2) s(-1) sr(-1) in the 10(8.5)-10(9.5) GeV energy bin. Simulations of the performance of the full detector are also described. The sensitivity of the full ARIANNA experiment is presented and compared with current neutrino flux models.
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7.
  • Cresswell, J. A., et al. (author)
  • Measurement of maternal functioning during pregnancy and postpartum: findings from the cross-sectional WHO pilot study in Jamaica, Kenya, and Malawi
  • 2020
  • In: BMC Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 20:1
  • Journal article (peer-reviewed)abstract
    • BackgroundThe World Health Organization's definition of maternal morbidity refers to "a negative impact on the woman's wellbeing and/or functioning". Many studies have documented the, mostly negative, effects of maternal ill-health on functioning. Although conceptually important, measurement of functioning remains underdeveloped, and the best way to measure functioning in pregnant and postpartum populations is unknown.MethodsA cross-sectional study among women presenting for antenatal (N=750) and postpartum (N=740) care in Jamaica, Kenya and Malawi took place in 2015-2016. Functioning was measured through the World Health Organization Disability Assessment Schedule (WHODAS-12). Data on health conditions and socio-demographic characteristics were collected through structured interview, medical record review, and clinical examination. This paper presents descriptive data on the distribution of functioning status among pregnant and postpartum women and examines the relationship between functioning and health conditions.ResultsWomen attending antenatal care had a lower level of functioning than those attending postpartum care. Women with a health condition or associated demographic risk factor were more likely to have a lower level of functioning than those with no health condition. However, the absolute difference in functioning scores typically remained modest.ConclusionsFunctioning is an important concept which integrates a woman-centered approach to examining how a health condition affects her life, and ultimately her return to functioning after delivery. However, the WHODAS-12 may not be the optimal tool for use in this population and additional components to capture pregnancy-specific issues may be needed. Challenges remain in how to integrate functioning outcomes into routine maternal healthcare at-scale and across diverse settings.
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9.
  • Sanchez, Erlan, et al. (author)
  • Association of plasma biomarkers with cognition, cognitive decline, and daily function across and within neurodegenerative diseases: Results from the Ontario Neurodegenerative Disease Research Initiative
  • 2024
  • In: Alzheimer's and Dementia. - 1552-5260 .- 1552-5279. ; 20:3, s. 1753-1770
  • Journal article (peer-reviewed)abstract
    • INTRODUCTION: We investigated whether novel plasma biomarkers are associated with cognition, cognitive decline, and functional independence in activities of daily living across and within neurodegenerative diseases. METHODS: Glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), phosphorylated tau (p-tau)181 and amyloid beta (Aβ)42/40 were measured using ultra-sensitive Simoa immunoassays in 44 healthy controls and 480 participants diagnosed with Alzheimer's disease/mild cognitive impairment (AD/MCI), Parkinson's disease (PD), frontotemporal dementia (FTD) spectrum disorders, or cerebrovascular disease (CVD). RESULTS: GFAP, NfL, and/or p-tau181 were elevated among all diseases compared to controls, and were broadly associated with worse baseline cognitive performance, greater cognitive decline, and/or lower functional independence. While GFAP, NfL, and p-tau181 were highly predictive across diseases, p-tau181 was more specific to the AD/MCI cohort. Sparse associations were found in the FTD and CVD cohorts and for Aβ42/40. DISCUSSION: GFAP, NfL, and p-tau181 are valuable predictors of cognition and function across common neurodegenerative diseases, and may be useful in specialized clinics and clinical trials.
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