| 1. |
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| 2. |
- Beral, V, et al.
(författare)
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Alcohol, tobacco and breast cancer - collaborative reanalysis of individual data from 53 epidemiological studies, including 58515 women with breast cancer and 95067 women without the disease
- 2002
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 87, s. 1234-45
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Tidskriftsartikel (refereegranskat)abstract
- Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58515 women with invasive breast cancer and 95067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19 - 1.45, P < 0.00001) for an intake of 35 - 44 g per day alcohol, and 1.46 (1.33 - 1.61, P < 0.00001) for greater than or equal to 45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1 % per 10 g per day, P < 0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers= 1.03, 95% CI 0.98 - 1.07, and for current smokers=0.99, 0.92 - 1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver. (C) 2002 Cancer Research UK.
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| 3. |
- Graff, M., et al.
(författare)
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Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults
- 2017
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Ingår i: PLoS Genet. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by similar to 30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
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| 4. |
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| 5. |
- Pantazis, N, et al.
(författare)
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Determining the likely place of HIV acquisition for migrants in Europe combining subject-specific information and biomarkers data
- 2019
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Ingår i: Statistical methods in medical research. - : SAGE Publications. - 1477-0334 .- 0962-2802. ; 28:7, s. 1979-1997
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Tidskriftsartikel (refereegranskat)abstract
- In most HIV-positive individuals, infection time is only known to lie between the time an individual started being at risk for HIV and diagnosis time. However, a more accurate estimate of infection time is very important in certain cases. For example, one of the objectives of the Advancing Migrant Access to Health Services in Europe (aMASE) study was to determine if HIV-positive migrants, diagnosed in Europe, were infected pre- or post-migration. We propose a method to derive subject-specific estimates of unknown infection times using information from HIV biomarkers’ measurements, demographic, clinical, and behavioral data. We assume that CD4 cell count (CD4) and HIV-RNA viral load trends after HIV infection follow a bivariate linear mixed model. Using post-diagnosis CD4 and viral load measurements and applying the Bayes’ rule, we derived the posterior distribution of the HIV infection time, whereas the prior distribution was informed by AIDS status at diagnosis and behavioral data. Parameters of the CD4–viral load and time-to-AIDS models were estimated using data from a large study of individuals with known HIV infection times (CASCADE). Simulations showed substantial predictive ability (e.g. 84% of the infections were correctly classified as pre- or post-migration). Application to the aMASE study ( n = 2009) showed that 47% of African migrants and 67% to 72% of migrants from other regions were most likely infected post-migration. Applying a Bayesian method based on bivariate modeling of CD4 and viral load, and subject-specific information, we found that the majority of HIV-positive migrants in aMASE were most likely infected after their migration to Europe.
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| 6. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 9. |
- Khazov, D., et al.
(författare)
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FLASH SPECTROSCOPY : EMISSION LINES FROM THE IONIZED CIRCUMSTELLAR MATERIAL AROUND < 10-DAY-OLD TYPE II SUPERNOVAE
- 2016
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 818:1
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Tidskriftsartikel (refereegranskat)abstract
- Supernovae (SNe) embedded in dense circumstellar material (CSM) may show prominent emission lines in their early-time spectra (<= 10 days after the explosion), owing to recombination of the CSM ionized by the shock-breakout flash. From such spectra (flash spectroscopy), we can measure various physical properties of the CSM, as well as the mass-loss rate of the progenitor during the year prior to its explosion. Searching through the Palomar Transient Factory (PTF and iPTF) SN spectroscopy databases from 2009 through 2014, we found 12 SNe II showing flash-ionized (FI) signatures in their first spectra. All are younger than 10 days. These events constitute 14% of all 84 SNe in our sample having a spectrum within 10 days from explosion, and 18% of SNe. II observed at ages <5 days, thereby setting lower limits on the fraction of FI events. We classified as blue/featureless (BF) those events having a first spectrum that is similar to that of a blackbody, without any emission or absorption signatures. It is possible that some BF events had FI signatures at an earlier phase than observed, or that they lack dense CSM around the progenitor. Within 2 days after explosion, 8 out of 11 SNe in our sample are either BF events or show FI signatures. Interestingly, we found that 19 out of 21 SNe brighter than an absolute magnitude M-R = -18.2 belong to the FI or BF groups, and that all FI events peaked above M-R = -17.6 mag, significantly brighter than average SNe II.
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| 12. |
- Scott, D., et al.
(författare)
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Mid-calf skeletal muscle density and its associations with accelerometer-determined physical activity, bone health and incident 12-month falls in older adults : the healthy ageing initiative
- 2019
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Ingår i: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 30, s. S59-S59
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: To determine associations of mid-calf muscle density, an indicator of intramuscular fat infiltration, with objectively-determined physical activity, bone health and 12-month falls risk in community-dwelling older adults.Methods: 2167 community-dwelling Swedish men and women who participated in the Healthy Ageing Initiative study at age 70 were included in this analysis. Mid-calf muscle density (mg/cm3; higher values indicate lower intramuscular fat content) at the proximal tibia, and bone parameters at the distal and proximal tibia and radius, were assessed by peripheral quantitative computed tomography. Whole-body lean and fat mass, lumbar spine and total hip BMD were assessed by DXA. Participants completed the timed up-and-go (TUG) test, 7-day accelerometer measurements of physical activity intensity, and self-reported falls data were collected 6 and 12 months later.Results: Only moderate/vigorous intensity physical activity, not sedentary or light activity, was positively associated with mid-calf muscle density (B=0.002 mg/cm3 per minute; P<0.001). 258 (12%) participants experienced a fall within 12 months. After adjustment for confounders including sex, fasting glucose, average daily moderate/vigorous intensity physical activity, and total lean mass at baseline, each mg/cm3 increase in mid-calf muscle density was associated with 4% and 11% reduced likelihood of experiencing a fall or multiple falls, respectively (both P<0.05). The association with multiple falls remained significant after further adjustment for TUG time (OR: 0.91 95%CI: 0.83, 0.99). In multivariable models, mid-calf muscle density was not associated with total hip BMD, was negatively associated with lumbar spine BMD (B=-0.003, 95%CI -0.005, -0.003 g/cm2), and at the radius, was positively associated only with proximal cortical density (B=0.784, 95%CI 0.246, 1.323 mg/cm3). However, at the tibia, muscle density was positively associated with distal total and trabecular BMD, and also proximal total and cortical BMD, cortical thickness and stress-strain index (all P<0.05).Conclusions: Higher mid-calf muscle density is independently associated with decreased likelihood for multiple incident falls and appears to have localised positive effects on bone structure. Improvements in lower-limb muscle density may be achievable through increasing participation in moderate/vigorous intensity activity and could potentially reduce fracture risk in older adults.
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| 13. |
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| 14. |
- Ebeling, M, et al.
(författare)
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Occupational differences in mortality and life expectancy persist after retirement and throughout life
- 2023
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Ingår i: Scandinavian journal of public health. - : SAGE Publications. - 1651-1905 .- 1403-4948. ; 51:6, s. 894-901
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Tidskriftsartikel (refereegranskat)abstract
- There are substantial differences in remaining life expectancy at higher ages between occupational groups. These differences may be the effect of work-related exposures, lifestyle factors of workers in specific occupations, socioeconomic position or a combination of this. The scope of this paper is the extent to which occupational differences in remaining life expectancy persist after retirement, which would suggest that occupational exposures alone are not likely to explain all the difference. Methods: All individuals born between 1925 and 1939 who reported occupational information in the Census 1985 and were residents in Sweden to the end of 2020 or who died were included and followed for death until 2020. The Nordic Classification of Occupations was used to create nine occupational groups. Partial life expectancy and age-specific death rates were applied to examine mortality differentials. Results: This study showed substantial differences in partial life expectancy across the occupational cohorts with the biggest difference being about 2 years. The mortality differences persisted with increasing age, both when measured as absolute numbers as well as relative numbers. Conclusions: The lack of convergence in mortality at high ages suggests that factors associated with lifestyle may play a larger role than occupational factors for the mortality differences between occupational groups at high ages. However, it cannot be ruled out that long-lasting effects of earlier occupational exposures also contribute. Regardless of the exact mechanism, we conclude that there is room for further reduction in mortality at high ages and, thus, for further improvement in life expectancy.
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| 15. |
- Ebeling, P, et al.
(författare)
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Role of biochemical markers in the management of osteoporosis
- 2001
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Ingår i: Best Practice & Research: Clinical Rheumatology. - : Elsevier BV. - 1532-1770 .- 1521-6942. ; 15:3, s. 385-400
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Tidskriftsartikel (refereegranskat)abstract
- Several serum and urine biochemical markers of bone resorption and formation have been developed. Biochemical bone markers have been used as intermediate end-points in all major studies of anti-osteoporotic therapies. Bone resorption markers, in particular, may add an independent, predictive value to the assessment of bone loss and fracture risk. There are also potential advantages in monitoring anti-osteoporotic treatment in the short-term in addition to bone densitometry, to rapidly identify non-responders to therapy, or non-compliance. Despite these recent advances, until now bone markers have simply been very useful research tools, with their clinical utility being limited by intra-individual and diurnal variability. However, the probability of the true bone mineral density response to hormone replacement therapy for the individual patient may be predicted using algorithms based on a spectrum of cut-off bone marker levels with varying false positive and negative rates. Thus, the transition of biochemical bone markers into everyday clinical practice may be rapidly approaching.
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| 16. |
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| 17. |
- Lundgren, S, et al.
(författare)
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Somatic mutations in lymphocytes in patients with immune-mediated aplastic anemia
- 2021
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 35:115, s. 1365-1379
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence and functional impact of somatic mutations in nonleukemic T cells is not well characterized, although clonal T-cell expansions are common. In immune-mediated aplastic anemia (AA), cytotoxic T-cell expansions are shown to participate in disease pathogenesis. We investigated the mutation profiles of T cells in AA by a custom panel of 2533 genes. We sequenced CD4+ and CD8+ T cells of 24 AA patients and compared the results to 20 healthy controls and whole-exome sequencing of 37 patients with AA. Somatic variants were common both in patients and healthy controls but enriched to AA patients’ CD8+ T cells, which accumulated most mutations on JAK-STAT and MAPK pathways. Mutation burden was associated with CD8+ T-cell clonality, assessed by T-cell receptor beta sequencing. To understand the effect of mutations, we performed single-cell sequencing of AA patients carrying STAT3 or other mutations in CD8+ T cells. STAT3 mutated clone was cytotoxic, clearly distinguishable from other CD8+ T cells, and attenuated by successful immunosuppressive treatment. Our results suggest that somatic mutations in T cells are common, associate with clonality, and can alter T-cell phenotype, warranting further investigation of their role in the pathogenesis of AA.
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| 18. |
- Micai, M, et al.
(författare)
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Autistic Adult Health and Professional Perceptions of It: Evidence From the ASDEU Project
- 2021
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Ingår i: Frontiers in psychiatry. - : Frontiers Media SA. - 1664-0640. ; 12, s. 614102-
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Tidskriftsartikel (refereegranskat)abstract
- The Autism Spectrum Disorders in the European Union (ASDEU) survey investigated the knowledge and health service experiences of users and providers to generate new hypotheses and scientific investigations that would contribute to improvement in health care for autistic adults. An online survey designed for autistic adults, carers of autistic adults, and professionals in adult services was translated into 11 languages and distributed electronically by organizations and in-country adult service facilities in 2017; 522 autistic adults, 442 carers, and 113 professionals provided answers to the health questions. Professionals, the majority in non-medical services, appeared to be poorly informed about whether certain co-occurring conditions were more frequent in autistic adults than typical adults—especially some medical conditions, suicide attempts, accidents, and pain. A minority of autistic adults reported preventive health behaviors such as routine health check-ups. The majority of users and providers expressed the desire to make health care services more user-friendly for autistic adults. Among the three groups, <20% of responders knew an organization or clinician which has developed a way to monitor health, and prevent poor health, that works well for adults on the autism spectrum. The results point to means for better management of co-occurring conditions associated with autism in adulthood in order to reduce hospital admissions and potential areas of improvement in health and social services for autistic adults. Specifically, efforts should be focused on (1) professionals' education on risks for co-occurring conditions in autistic adults; (2) promoting preventive health behaviors; (3) making services user-friendly for autistic adults and their families; and (4) encouraging knowledge of good local services.
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| 19. |
- Micai, M, et al.
(författare)
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Autistic Adult Services Availability, Preferences, and User Experiences: Results From the Autism Spectrum Disorder in the European Union Survey
- 2022
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Ingår i: Frontiers in psychiatry. - : Frontiers Media SA. - 1664-0640. ; 13, s. 919234-
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Tidskriftsartikel (refereegranskat)abstract
- There is very little knowledge regarding autistic adult services, practices, and delivery. The study objective was to improve understanding of current services and practices for autistic adults and opportunities for improvement as part of the Autism Spectrum Disorder in the European Union (ASDEU) project. Separate survey versions were created for autistic adults, carers of autistic adults, and professionals in adult services. 2,009 persons responded to the survey and 1,085 (54%) of them completed at least one of the services sections: 469 autistic adults (65% female; 55% <35 years old), 441 carers of autistic adults (27% female; 6% <35 years old), 175 professionals in adult services (76% female; 67% in non-medical services). Top choices by autistic adults, carers or professionals for services best suiting their current needs were: residential services: “help in own home” (adults, carers of high independent adults, professionals), “fulltime residential facility” (carers of low independent adults); employment services: “job mentors” (adults, carers of high independent adults, professionals), “Sheltered employment” (carers of low independent adults); education services: “support in regular education setting” (all groups); financial services: financial support in lieu of employment (“Supplementary income for persons unable to have full employment” for adults, “full pension” for carers of low independent adults) or to supplement employment earnings for carers of high independent adults and professionals; social services: “behavior training” (adults) and “life skills training” (carers and professionals). Waiting times for specific services were generally < 1 month or 1–3 months, except for residential services which could be up to 6 months; most professionals were uninformed of waiting times (>50% responded “don’t know”). Five of seven residential services features recommended for autistic adults were experienced by <50% of adults. The knowledge of good local services models that work well for autistic adults was generally low across all services areas. The variation in services experiences and perceptions reported by autistic adults, carers, or professionals underscore the need to query all groups for a complete picture of community services availability and needs. The results showed areas for potential improvement in autistic adult services delivery in the EU to achieve recommended standards.
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| 20. |
- Micai, M, et al.
(författare)
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Intervention Services for Autistic Adults: An ASDEU Study of Autistic Adults, Carers, and Professionals' Experiences
- 2022
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Ingår i: Journal of autism and developmental disorders. - : Springer Science and Business Media LLC. - 1573-3432 .- 0162-3257. ; 52:4, s. 1623-1639
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Tidskriftsartikel (refereegranskat)abstract
- The Autism Spectrum Disorders in the European Union (ASDEU) survey investigated local services’ use experiences of autistic adults, carers and professionals with interventions for autistic adults. The majority of the 697 participants experienced recommended considerations prior to deciding on intervention and during the intervention plan and implementation. Psychosocial interventions were the most commonly experienced interventions, while pharmacological interventions NOT recommended for core autistic symptoms were reported by fairly large proportions of participants. Family interventions were experienced slightly more commonly by carers than adults or professionals. Less than the 26% of autistic adult responders who had experienced challenging behaviors reported receiving an intervention to change them. These results provide insights for improving gaps in service provision of interventions among autistic adults.
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| 23. |
- Scattoni, ML, et al.
(författare)
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Real-World Experiences in Autistic Adult Diagnostic Services and Post-diagnostic Support and Alignment with Services Guidelines: Results from the ASDEU Study
- 2021
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Ingår i: Journal of autism and developmental disorders. - : Springer Science and Business Media LLC. - 1573-3432 .- 0162-3257. ; 51:11, s. 4129-4146
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Tidskriftsartikel (refereegranskat)abstract
- Research providing an evidence-base for autistic adult services is sparse. The Autism Spectrum Disorders in the European Union (ASDEU) network implemented an on-line survey to determine gaps in autistic adult diagnostic evaluation and post-diagnostic support services. More than 55% in all groups experienced most of the recommended features for diagnostic evaluation for autistic adults. In contrast, < 2% of adults or carers, and < 21% of professionals experienced each of the recommended features for post-diagnostic support. In contrast to 61% of professionals, only about 30% of autistic adults and carers had knowledge of good local services models for autism diagnosis in adulthood. There are major differences between good practice guidelines for diagnostic and post-diagnostic care for autistic adults, and what is actually experienced by services users and professionals.
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