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- Beral, V., et al.
(författare)
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Ovarian cancer and smoking: individual participant meta-analysis including 28 114 women with ovarian cancer from 51 epidemiological studies
- 2012
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Ingår i: The Lancet Oncology. - 1474-5488. ; 13:9, s. 946-956
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Tidskriftsartikel (refereegranskat)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subtypes and on overall ovarian cancer risk are unclear, and the findings from most studies with relevant data are unpublished. To assess these associations, we review the published and unpublished evidence.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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| 2. |
- Beral, V., et al.
(författare)
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Ovarian Cancer and Body Size : Individual Participant Meta-Analysis Including 25,157 Women with Ovarian Cancer from 47 Epidemiological Studies
- 2012
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Ingår i: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 9:4
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Tidskriftsartikel (refereegranskat)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. |
- Craddock, Nick, et al.
(författare)
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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
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Tidskriftsartikel (refereegranskat)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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| 6. |
- Cicardi, M., et al.
(författare)
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Icatibant, a New Bradykinin-Receptor Antagonist, in Hereditary Angioedema
- 2010
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 363:6, s. 532-541
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist. METHODS In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms. RESULTS A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P=0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported. CONCLUSIONS In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)
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| 8. |
- Adams, Marc A., et al.
(författare)
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Patterns of neighborhood environment attributes related to physical activity across 11 countries : a latent class analysis
- 2013
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Ingår i: International Journal of Behavioral Nutrition and Physical Activity. - : Springer Science and Business Media LLC. - 1479-5868. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neighborhood environment studies of physical activity (PA) have been mainly single-country focused. The International Prevalence Study (IPS) presented a rare opportunity to examine neighborhood features across countries. The purpose of this analysis was to: 1) detect international neighborhood typologies based on participants' response patterns to an environment survey and 2) to estimate associations between neighborhood environment patterns and PA. Methods: A Latent Class Analysis (LCA) was conducted on pooled IPS adults (N=11,541) aged 18 to 64 years old (mean=37.5 +/- 12.8 yrs; 55.6% women) from 11 countries including Belgium, Brazil, Canada, Colombia, Hong Kong, Japan, Lithuania, New Zealand, Norway, Sweden, and the U. S. This subset used the Physical Activity Neighborhood Environment Survey (PANES) that briefly assessed 7 attributes within 10-15 minutes walk of participants' residences, including residential density, access to shops/services, recreational facilities, public transit facilities, presence of sidewalks and bike paths, and personal safety. LCA derived meaningful subgroups from participants' response patterns to PANES items, and participants were assigned to neighborhood types. The validated short-form International Physical Activity Questionnaire (IPAQ) measured likelihood of meeting the 150 minutes/week PA guideline. To validate derived classes, meeting the guideline either by walking or total PA was regressed on neighborhood types using a weighted generalized linear regression model, adjusting for gender, age and country. Results: A 5-subgroup solution fitted the dataset and was interpretable. Neighborhood types were labeled, "Overall Activity Supportive (52% of sample)", "High Walkable and Unsafe with Few Recreation Facilities (16%)", "Safe with Active Transport Facilities (12%)", "Transit and Shops Dense with Few Amenities (15%)", and "Safe but Activity Unsupportive (5%)". Country representation differed by type (e. g., U. S. disproportionally represented "Safe but Activity Unsupportive"). Compared to the Safe but Activity Unsupportive, two types showed greater odds of meeting PA guideline for walking outcome (High Walkable and Unsafe with Few Recreation Facilities, OR=2.26 (95% CI 1.18-4.31); Overall Activity Supportive, OR=1.90 (95% CI 1.13-3.21). Significant but smaller odds ratios were also found for total PA. Conclusions: Meaningful neighborhood patterns generalized across countries and explained practical differences in PA. These observational results support WHO/UN recommendations for programs and policies targeted to improve features of the neighborhood environment for PA.
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| 9. |
- Bos, Peter MJ, et al.
(författare)
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Human risk assessment of single exposure in chemical incidents : present situation and new and increasing chemical incident scenarios
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The release of chemicals from their containment, either accidentally or deliberately, is one of the most relevant risk scenarios in Europe. A human health risk assessment is a prerequisite for chemical incident prevention, preparedness and response. European guidance and harmonized Acute Exposure Reference Values (AERVs) are urgently needed for effective human health risk assessment in the context of chemical incidents.At present, no broad European consensus is available on guidance for risk assessment, risk management and risk communication purposes in case of chemical incidents. A review of legislation, existing or currently under revision, suggests that harmonized European guidance is not expected to be developed in the short term. An increasing number of European countries are developing their own procedures to assess the human health risk of chemical incident scenarios. The AERVs thus produced serve different purposes and are not interchangeable. Lack of international harmonization seriously obstructs a consistent response in chemical emergencies with transboundary effects within and beyond the EU, will hamper multinational companies attempting to make consistent risk assessments worldwide and will hinder consistent and transparent assessment, and management and communication of risks by different stakeholders.Emerging chemical incident risk scenarios and risk drivers have been identified. It is recommended to monitor more frequently at an early stage for new trends in chemicals, scenarios and risks from chemical incidents. A need for a specific approach to deal with single exposure to mixtures of chemicals is identified, as well as for specific guidance to adequately protect professional first responders.
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| 10. |
- Bull, Peter, et al.
(författare)
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Förstudie obemannade farkoster
- 2012
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Rapport (populärvet., debatt m.m.)abstract
- Obemannade farkoster används allt oftare, och i allt fler roller, i dagens kon- flikter. Denna rapport ger en bred överblick över området militära obemannade farkoster, samt rekommendationer för inriktningen av framtida FoU-satsningar inom området.Överblicken över området har fokus på både system, förmågor och verksam- heter som är relevanta för Försvarsmakten. Genom att låta de insatsförmågor som definieras i FMUP (Försvarsmaktens utvecklingsplan) gå som en röd tråd genom rapporten, både när specifika system diskuteras och när möjliga scena- rier där obemannade farkoster kan vara till nytta beskrivs, har vi försökt hålla både bredd och relevans i dokumentet.Rekommendationerna vilar på en genomgång av de inriktningsdokument som producerats i Försvarsmakten, t.ex. Perspektivplanneringen och FMUP, besök vid de enheter som dagligen använder obemannade farkoster, UAV-enheten i Karlsborg och Swedec i Eksjö, samt den områdesöverblick som nämns ovan. Slutsatserna är att den effektivaste kompetensuppbyggnaden och kunskapsöver- föringen fås om man skapar breda tvärvetenskapliga projekt inom respektive systemkategori (UAV, UGV, etc) med nära kontakter till materielförsörjnings- processen och perspektivplaneringen. Dessa kan samla kompetensen inom FHS och FOI, övervaka forskningsfronten genom att bevaka tävlingar, konferenser samt delta i internationella samarbeten, samt överföra det samlade resultaten till Försvarsmakten genom demonstrationer av verkliga eller simulerade delsy- stem och interaktiva simuleringar av hela system. Just systemsimuleringar kan göras särskilt realistiska, eftersom interaktionen med de riktiga obemannade systemen till stor del sker igenom kontrollstationernas datorer. På så sätt ska- pas en känsla för både hot och möjligheter med de nya systemen, vilket gagnar både taktikutveckling och materielprocesser.
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