| 1. |
- Schael, S., et al.
(författare)
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Electroweak measurements in electron positron collisions at W-boson-pair energies at LEP
- 2013
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 532:4, s. 119-244
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Forskningsöversikt (refereegranskat)abstract
- Electroweak measurements performed with data taken at the electron positron collider LEP at CERN from 1995 to 2000 are reported. The combined data set considered in this report corresponds to a total luminosity of about 3 fb(-1) collected by the four LEP experiments ALEPH, DELPHI, 13 and OPAL, at centre-of-mass energies ranging from 130 GeV to 209 GeV. Combining the published results of the four LEP experiments, the measurements include total and differential cross-sections in photon-pair, fermion-pair and four-fermion production, the latter resulting from both double-resonant WW and ZZ production as well as singly resonant production. Total and differential cross-sections are measured precisely, providing a stringent test of the Standard Model at centre-of-mass energies never explored before in electron positron collisions. Final-state interaction effects in four-fermion production, such as those arising from colour reconnection and Bose Einstein correlations between the two W decay systems arising in WW production, are searched for and upper limits on the strength of possible effects are obtained. The data are used to determine fundamental properties of the W boson and the electroweak theory. Among others, the mass and width of the W boson, m(w) and Gamma(w), the branching fraction of W decays to hadrons, B(W -> had), and the trilinear gauge-boson self-couplings g(1)(Z), K-gamma and lambda(gamma), are determined to be: m(w) = 80.376 +/- 0.033 GeV Gamma(w) = 2.195 +/- 0.083 GeV B(W -> had) = 67.41 +/- 0.27% g(1)(Z) = 0.984(-0.020)(+0.018) K-gamma - 0.982 +/- 0.042 lambda(gamma) = 0.022 +/- 0.019. (C) 2013 Elsevier B.V. All rights reserved.
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| 2. |
- Palmer, Nicholette D, et al.
(författare)
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A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
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Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
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Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
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| 3. |
- Dik, Vincent K., et al.
(författare)
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Coffee and tea consumption, genotype- based CYP1A2 and NAT2 activity and colorectal cancer risk- Results from the EPIC cohort study
- 2014
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 135:2, s. 401-412
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Tidskriftsartikel (refereegranskat)abstract
- Coffee and tea contain numerous antimutagenic and antioxidant components and high levels of caffeine that may protect against colorectal cancer (CRC). We investigated the association between coffee and tea consumption and CRC risk and studied potential effect modification by CYP1A2 and NAT2 genotypes, enzymes involved in the metabolization of caffeine. Data from 477,071 participants (70.2% female) of the European Investigation into Cancer and Nutrition (EPIC) cohort study were analyzed. At baseline (1992-2000) habitual (total, caffeinated and decaffeinated) coffee and tea consumption was assessed with dietary questionnaires. Cox proportional hazards models were used to estimate adjusted hazard ratio's (HR) and 95% confidence intervals (95% CI). Potential effect modification by genotype-based CYP1A2 and NAT2 activity was studied in a nested case-control set of 1,252 cases and 2,175 controls. After a median follow-up of 11.6 years, 4,234 participants developed CRC (mean age 64.78.3 years). Total coffee consumption (high vs. non/low) was not associated with CRC risk (HR 1.06, 95% CI 0.95-1.18) or subsite cancers, and no significant associations were found for caffeinated (HR 1.10, 95% CI 0.97-1.26) and decaffeinated coffee (HR 0.96, 95% CI 0.84-1.11) and tea (HR 0.97, 95% CI 0.86-1.09). High coffee and tea consuming subjects with slow CYP1A2 or NAT2 activity had a similar CRC risk compared to non/low coffee and tea consuming subjects with a fast CYP1A2 or NAT2 activity, which suggests that caffeine metabolism does not affect the link between coffee and tea consumption and CRC risk. This study shows that coffee and tea consumption is not likely to be associated with overall CRC. What's new? Coffee and tea contain numerous compounds that may protect against colorectal cancer (CRC). In this study of more than 475,000 participants over more than a decade, the authors investigated whether coffee or tea consumption is associated with an altered risk of developing CRC. They also asked whether genetic variations in two enzymes involved in caffeine metabolism (CYP1A2 and NAT2) might affect this risk. They conclude that neither consumption patterns, nor genetic differences in caffeine metabolism, appear to have a significant impact on CRC risk.
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| 4. |
- Dik, Vincent K, et al.
(författare)
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Prediagnostic intake of dairy products and dietary calcium and colorectal cancer survival - results from the EPIC cohort study.
- 2014
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755 .- 1055-9965. ; 23:9, s. 1813-1823
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Tidskriftsartikel (refereegranskat)abstract
- Background We investigated whether prediagnostic reported intake of dairy products and dietary calcium are associated with colorectal cancer (CRC) survival. Methods Data from 3,859 subjects with CRC (42.1% male, mean age at diagnosis 64.2 ± 8.1 years) in the European Investigation into Cancer and Nutrition (EPIC) cohort were analyzed. Intake of dairy products and dietary calcium was assessed at baseline (1992-2000) using validated, country-specific dietary questionnaires. Multivariable Cox regression models were used to calculate hazard ratios (HR) and corresponding 95% confidence intervals (95%-CI) for CRC specific death (n=1,028) and all-cause death (n=1,525) for different quartiles of intake. Results The consumption of total dairy products was not statistically significantly associated with risk of CRC-specific death (adjusted HR Q4 vs. Q1: 1.17 95%-CI 0.97-1.43) nor of all-cause death (Q4 vs. Q1: 1.16 95%-CI 0.98-1.36). Multivariable adjusted HRs for CRC-specific death (Q4 vs. Q1) were 1.21 (95%-CI 0.99-1.48) for milk, 1.09 (95%-CI 0.88-1.34) for yoghurt and 0.93 (95%-CI 0.76-1.14) for cheese. The intake of dietary calcium was not associated with the risk of CRC-specific (adjusted HR Q4 vs. Q1: 1.01 95%-CI 0.81-1.26) nor of all-cause death (Q4 vs. Q1: 1.01 95%-CI 0.84-1.21). Conclusions The prediagnostic reported intake of dairy products and dietary calcium are not associated with disease-specific or all-cause risk of death in patients diagnosed with CRC. Impact The impact of diet on cancer survival is largely unknown. This study shows that despite it's inverse association with CRC risk, the prediagnostic intake of dairy and dietary calcium do not affect CRC survival.
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| 5. |
- Albrechtsen, A., et al.
(författare)
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Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes
- 2013
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 56:2, s. 298-310
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Tidskriftsartikel (refereegranskat)abstract
- Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) > 1% with common metabolic phenotypes. The study comprised three stages. We performed medium-depth (8x) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI > 27.5 kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p < 0.05) with case-control status, from four selected annotation categories or from loci reported to associate with metabolic traits. These variants were genotyped in 15,989 Danes to search for association with 12 metabolic phenotypes (stage 2). In stage 3, polymorphisms showing potential associations were genotyped in a further 63,896 Europeans. Exome sequencing identified 70,182 polymorphisms with MAF > 1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 x 10(-14)), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p = 1.2 x 10(-11)) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p = 8.2 x 10(-10)). We applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits.
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| 6. |
- Leenders, Max, et al.
(författare)
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Fruit and Vegetable Consumption and Mortality European Prospective Investigation Into Cancer and Nutrition
- 2013
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 178:4, s. 590-602
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Tidskriftsartikel (refereegranskat)abstract
- In this study, the relation between fruit and vegetable consumption and mortality was investigated within the European Prospective Investigation Into Cancer and Nutrition. Survival analyses were performed, including 451,151 participants from 10 European countries, recruited between 1992 and 2000 and followed until 2010. Hazard ratios, rate advancement periods, and preventable proportions to respectively compare risk of death between quartiles of consumption, to estimate the period by which the risk of death was postponed among high consumers, and to estimate proportions of deaths that could be prevented if all participants would shift their consumption 1 quartile upward. Consumption of fruits and vegetables was inversely associated with all-cause mortality (for the highest quartile, hazard ratio = 0.90, 95% confidence interval (CI): 0.86, 0.94), with a rate advancement period of 1.12 years (95% CI: 0.70, 1.54), and with a preventable proportion of 2.95%. This association was driven mainly by cardiovascular disease mortality (for the highest quartile, hazard ratio = 0.85, 95% CI: 0.77, 0.93). Stronger inverse associations were observed for participants with high alcohol consumption or high body mass index and suggested in smokers. Inverse associations were stronger for raw than for cooked vegetable consumption. These results support the evidence that fruit and vegetable consumption is associated with a lower risk of death.
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| 7. |
- Zamora-Ros, R., et al.
(författare)
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Tea and coffee consumption and risk of esophageal cancer: The European prospective investigation into cancer and nutrition study
- 2014
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 135:6, s. 1470-1479
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiological data regarding tea and coffee consumption and risk of esophageal cancer (EC) is still inconclusive. We examined the association of tea and coffee consumption with EC risk among 442,143 men and women without cancer at baseline from 9 countries of the European Prospective Investigation into Cancer and Nutrition. Tea and coffee intakes were recorded using country-specific validated dietary questionnaires. Cox regression models were used to analyze the relationships between tea and coffee intake and EC risk. During a mean follow-up of 11.1 years, 339 participants developed EC, of which 142 were esophageal adenocarcinoma (EAC) and 174 were esophageal squamous cell carcinoma (ESCC). In the multivariable models, no significant associations between tea (mostly black tea), and coffee intake and risk of EC, EAC and ESCC were observed. In stratified analyses, among men coffee consumption was inversely related to ESCC (HR for comparison of extreme tertiles 0.42, 95% CI 0.20-0.88; p-trend = 0.022), but not among women. In current smokers, a significant and inverse association was observed between ESCC risk and tea (HR 0.46, 95% CI 0.23-0.93; p-trend = 0.053) and coffee consumption (HR 0.37, 95% CI 0.19-0.73; p-trend = 0.011). However, no statistically significant findings were observed using the continuous variable (per 100 mL/d). These data did not show a significant association between tea and coffee consumption and EC, EAC and ESCC, although a decreased risk of ESCC among men and current smokers is suggested, but need to be confirmed in further prospective studies including more cases.
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| 8. |
- Brownstein, Catherine A., et al.
(författare)
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An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- 2014
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
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| 9. |
- Michaud, Dominique S, et al.
(författare)
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Coffee and tea intake and risk of brain tumors in the European prospective investigation into cancer and nutrition (EPIC) cohort study
- 2010
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Ingår i: American Journal of Clinical Nutrition. - : American Society for Nutrition. - 0002-9165 .- 1938-3207. ; 92:5, s. 1145-1150
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Tidskriftsartikel (refereegranskat)abstract
- Background: In a recent US cohort study, total coffee and tea consumption was inversely associated with risk of glioma, and experimental studies showed that caffeine can slow the invasive growth of glioblastoma.Objective: The objective was to examine the relation between coffee and tea intake and the risk of glioma and meningioma in a large European cohort study, the European Prospective Investigation into Cancer and Nutrition (EPIC).Design: Data on coffee and tea intake were collected from men and women recruited into the EPIC cohort study. Over an average of 8.5 y of follow-up, 343 cases of glioma and 245 cases of meningioma were newly diagnosed in 9 countries. We used Cox proportional hazards models to examine the relation between coffee and tea and brain tumors.Results: We observed no associations between coffee, tea, or combined coffee and tea consumption and risk of either type of brain tumor when using quantiles based on country-specific distributions of intake. However, a significant inverse association was observed for glioma risk among those consuming ≥100 mL coffee and tea per day compared with those consuming <100 mL/d (hazard ratio: 0.66; 95% CI: 0.44, 0.97; P = 0.03). The association was slightly stronger in men (hazard ratio: 0.59; 95% CI: 0.34, 1.01) than in women (hazard ratio: 0.74; 95% CI: 0.42, 1.31), although neither was statistically significant.Conclusions: In this large cohort study, we observed an inverse association between total coffee and tea consumption and risk of glioma that was consistent with the findings of a recent study. These findings, if further replicated in other studies, may provide new avenues of research on gliomas.
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| 10. |
- Sjödahl Hammarlund, Catharina, et al.
(författare)
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Motor and non-motor predictors of illness-related distress in Parkinson's disease
- 2012
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Ingår i: Parkinsonism & Related Disorders. - : Elsevier. - 1353-8020 .- 1873-5126. ; 18:3, s. 299-302
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To identify motor and non-motor symptoms independently associated with distress in Parkinson's disease (PD).METHOD: Clinical and patient-reported data from 118 people with PD (mean age and PD-duration, 64 and 8 years) were analyzed regarding associations with patient-reported distress using multiple regressions (controlling for age).RESULTS: Non-motor symptoms independently associated with distress were pain, fatigue, sleep, depression and anxiety (R(2), 0.81). The only significant motor aspect was mobility (R(2), 0.31). When considering both motor and non-motor symptoms, fatigue, pain, depression and sleep showed independent associations with distress (R(2), 0.76).CONCLUSION: Distress in PD is primarily associated with non-motor features.
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| 11. |
- Thompson, Paul M., et al.
(författare)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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| 12. |
- Buckland, G., et al.
(författare)
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Adherence to the Mediterranean diet and risk of bladder cancer in the EPIC cohort study
- 2014
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 134:10, s. 2504-2511
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Tidskriftsartikel (refereegranskat)abstract
- There is growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, to date no epidemiological study has investigated the influence of the MD on bladder cancer. We evaluated the association between adherence to the MD and risk of urothelial cell bladder cancer (UCC), according to tumor aggressiveness, in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 477,312 participants, recruited from ten European countries between 1991 and 2000. Information from validated dietary questionnaires was used to develop a relative Mediterranean diet score (rMED), including nine dietary components. Cox regression models were used to assess the effect of the rMED on UCC risk, while adjusting for dietary energy and tobacco smoking of any kind. Stratified analyses were performed by sex, BMI, smoking status, European region and age at diagnosis. During an average follow-up of 11 years, 1,425 participants (70.9% male) were diagnosed with a first primary UCC. There was a negative but non-significant association between a high versus low rMED score and risk of UCC overall (HR: 0.84 [95% CI 0.69, 1.03]) and risk of aggressive (HR: 0.88 [95% CI 0.61, 1.28]) and non-aggressive tumors (HR: 0.78 [95% CI 0.54, 1.14]). Although there was no effect modification in the stratified analyses, there was a significant 34% (p = 0.043) decreased risk of UCC in current smokers with a high rMED score. In EPIC, the MD was not significantly associated with risk of UCC, although we cannot exclude that a MD may reduce risk in current smokers. What's new? Urothelial cell carcinoma (UCC) is the most common form of bladder cancer. Previous studies suggested that plasma carotenoids, antioxidants found in fruit and vegetables, were associated with a decreased risk of UCC while a high intake of animal protein was associated with an increased cancer risk. Here, the authors conducted the first study to investigate the association between the Mediterranean diet, a diet rich in fresh fruits and vegetables and low in animal products, and UCC in Europe. They found that adherence to a Mediterranean diet was not significantly associated with UCC, regardless of level of tumour aggressiveness. They point out that these findings are in line with the rather weak evidence for questionnaire-based associations between dietary factors and bladder cancer risk.
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| 13. |
- Hamad, Osama A., 1978-, et al.
(författare)
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Contribution of chondroitin sulfate A to the binding of complement proteins to activated platelets
- 2010
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:9, s. e12889-
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Tidskriftsartikel (refereegranskat)abstract
- Exposure of chondroitin sulfate A (CS-A) on the surface of activated platelets is well established. The aim of the present study was to investigate to what extent CS-A contributes to the binding of C1q and the complement regulators C1 inhibitor (C1INH), C4b-binding protein (C4BP), and factor H to platelets. Human serum was passed over Sepharose conjugated with CS-A, and bound proteins were identified by Western blotting, and mass spectrometric analysis. C1q was identified as the main protein that specifically bound to CS-A, but C4BP and factor H were also shown to interact. Binding of C1INH was dependent of the presence of C1q and not bound to CS-A from C1q-depleted serum. The specific interactions observed of these proteins with CS-A were subsequently confirmed by surface plasmon resonance analysis using purified proteins. Importantly, C1q, C4BP, and factor H were shown to bind also to activated platelets and this interaction was inhibited by a CS-A-specific monoclonal antibody, thereby linking the binding of C1q, C4BP, and factor H to exposure of CS-A on platelets. CS-A-bound C1q was also shown to amplify the binding of model immune complexes to both microtiter plate-bound CS-A and to activated platelets. In conclusion, this study supports the concept that CS-A contributes to the binding of C1q, C4BP, and factor H to platelets, thereby adding CS-A to the previously reported binding sites for these proteins on the platelet surface. CS-A-bound C1q seems to amplify the binding of immune complexes to activated platelets, suggesting a role for this molecule in immune complex diseases.
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| 14. |
- Hosnijeh, Fatemeh Saberi, et al.
(författare)
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Prediagnostic telomere length and risk of B-cell lymphoma-Results from the EPIC cohort study
- 2014
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 135:12, s. 2910-2917
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Tidskriftsartikel (refereegranskat)abstract
- Recent epidemiological investigations have reported on the association between telomere length (TL) and a number of malignancies, including B-cell lymphoma (BCL). The reported results for BCLs are however inconsistent. We carried out a nested case-control study to determine whether TL is associated with future risk of BCL. Using quantitative polymerase chain reaction, the relative TL (i.e. the ratio of telomere repeat copy number to single gene copy number) was measured in mononuclear cell DNA of prediagnostic peripheral blood samples of 464 lymphoma cases and 464 matched controls (median time between blood collection and diagnosis, 4.6 years). Conditional logistic regression was used to analyze the association between TL and the risk of developing lymphoma and histologic subtypes. TL was significantly longer in cases compared to controls (p 5 0.01). Multivariable models showed a significantly increased risk of BCL [odds ratio (OR) = 1.66, 1.80 and 3.20 for quartiles 2-4, respectively, p-trend = 0.001], diffuse large B-cell lymphoma (DLBCL) (OR = 1.20, 2.48 and 2.36 for quartiles 2-4, respectively, p-trend = 0.03) and follicular lymphoma (FL) (OR = 1.39, 1.90 and 2.69 for quartiles 2-4, respectively, p-trend = 0.02) with increasing TL. This study suggests an association between longer leucocyte TL and increased risk of BCL which was most pronounced for DLBCL and FL.
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| 15. |
- Langenberg, Claudia, et al.
(författare)
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Long-Term Risk of Incident Type 2 Diabetes and Measures of Overall and Regional Obesity: The EPIC-InterAct Case-Cohort Study
- 2012
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Ingår i: PLoS Medicine. - San Francisco : Public Library of Science (PLoS). - 1549-1676 .- 1549-1277. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Waist circumference (WC) is a simple and reliable measure of fat distribution that may add to the prediction of type 2 diabetes (T2D), but previous studies have been too small to reliably quantify the relative and absolute risk of future diabetes by WC at different levels of body mass index (BMI). Methods and Findings: The prospective InterAct case-cohort study was conducted in 26 centres in eight European countries and consists of 12,403 incident T2D cases and a stratified subcohort of 16,154 individuals from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. We used Prentice-weighted Cox regression and random effects meta-analysis methods to estimate hazard ratios for T2D. Kaplan-Meier estimates of the cumulative incidence of T2D were calculated. BMI and WC were each independently associated with T2D, with WC being a stronger risk factor in women than in men. Risk increased across groups defined by BMI and WC; compared to low normal weight individuals (BMI 18.5-22.4 kg/m(2)) with a low WC (< 94/80 cm in men/women), the hazard ratio of T2D was 22.0 (95% confidence interval 14.3; 33.8) in men and 31.8 (25.2; 40.2) in women with grade 2 obesity (BMI >= 35 kg/m(2)) and a high WC (> 102/88 cm). Among the large group of overweight individuals, WC measurement was highly informative and facilitated the identification of a subgroup of overweight people with high WC whose 10-y T2D cumulative incidence (men, 70 per 1,000 person-years; women, 44 per 1,000 person-years) was comparable to that of the obese group (50-103 per 1,000 person-years in men and 28-74 per 1,000 person-years in women). Conclusions: WC is independently and strongly associated with T2D, particularly in women, and should be more widely measured for risk stratification. If targeted measurement is necessary for reasons of resource scarcity, measuring WC in overweight individuals may be an effective strategy, since it identifies a high-risk subgroup of individuals who could benefit from individualised preventive action.
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| 16. |
- Ludvigsson, Johnny, et al.
(författare)
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GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus
- 2012
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 366:5, s. 433-442
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The 65-kD isoform of glutamic acid decarboxylase (GAD65) is a major autoantigen in type 1 diabetes. We hypothesized that alum-formulated GAD65 (GAD-alum) can preserve beta-cell function in patients with recent-onset type 1 diabetes.METHODS: We studied 334 patients, 10 to 20 years of age, with type 1 diabetes, fasting C-peptide levels of more than 0.3 ng per milliliter (0.1 nmol per liter), and detectable serum GAD65 autoantibodies. Within 3 months after diagnosis, patients were randomly assigned to receive one of three study treatments: four doses of GAD-alum, two doses of GAD-alum followed by two doses of placebo, or four doses of placebo. The primary outcome was the change in the stimulated serum C-peptide level (after a mixed-meal tolerance test) between the baseline visit and the 15-month visit. Secondary outcomes included the glycated hemoglobin level, mean daily insulin dose, rate of hypoglycemia, and fasting and maximum stimulated C-peptide levels.RESULTS: The stimulated C-peptide level declined to a similar degree in all study groups, and the primary outcome at 15 months did not differ significantly between the combined active-drug groups and the placebo group (P=0.10). The use of GAD-alum as compared with placebo did not affect the insulin dose, glycated hemoglobin level, or hypoglycemia rate. Adverse events were infrequent and mild in the three groups, with no significant differences.CONCLUSIONS: Treatment with GAD-alum did not significantly reduce the loss of stimulated C peptide or improve clinical outcomes over a 15-month period.
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| 17. |
- Rohrmann, S., et al.
(författare)
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The association of education with long-term weight change in the EPIC-PANACEA cohort
- 2012
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Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 66:8, s. 957-963
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/OBJECTIVES: Cross-sectionally, educational attainment is strongly associated with the prevalence of obesity, but this association is less clear for weight change during adult life. The objective of this study is to examine the association between educational attainment and weight change during adult life in the European Prospective Investigation into Cancer and Nutrition (EPIC). SUBJECTS/METHODS: EPIC is a cohort study with 361 467 participants and up to 10 years of follow-up. Educational attainment was categorized according to the highest obtained school level (primary school or less, vocational secondary training, other secondary education and university). Multivariate mixed-effects linear regression models were used to study education in relation to weight at age 20 years (self-reported), to annual change in weight between age 20 years and measured weight at recruitment, and to annual change in weight during follow-up time. RESULTS: Higher educational attainment was associated with on average a lower body mass index (BMI) at age 20 years and a lower increase in weight up to recruitment (highest vs lowest educational attainment in men: -60 g per year (95% confidence interval (CI) -80; -40), women -110 g per year (95% CI -130; -80)). Although during follow-up after recruitment an increase in body weight was observed in all educational levels, gain was lowest in men and women with a university degree (high vs low education -120 g per year (95% CI -150; -90) and -70 g per year (95% CI -90; -60), respectively). CONCLUSIONS: Existing differences in BMI between higher and lower educated individuals at early adulthood became more pronounced during lifetime, which possibly impacts on obesity-related chronic disease risk in persons with lower educational attainment.
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| 18. |
- Sjödahl Hammarlund, Catharina, et al.
(författare)
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Measuring outcomes in Parkinson's disease : a multi-perspective concept mapping study
- 2012
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Ingår i: Quality of Life Research. - : Springer. - 0962-9343 .- 1573-2649. ; 21:3, s. 453-463
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Tidskriftsartikel (refereegranskat)abstract
- To identify and develop a conceptual map of prioritized areas and to determine their relative importance for outcome measurement in clinical Parkinson's disease (PD) trials, from the perspectives of health care professionals and people with PD.METHOD:We used concept mapping, a qualitative/quantitative method consisting of three steps: item generation through focus groups (n = 27; 12 people with PD, 12 health care professionals, 3 researchers), item sorting and rating (n = 38; 19 people with PD, 19 health care professionals), and data analysis (multidimensional scaling, cluster analysis).RESULTS:Ninety-nine items and eight clusters were generated. Clusters representing Participation; Mobility and motor functioning; Cognitive and executive functioning; and Emotions were the most homogenous. Statements within clusters representing Energy and abilities; Autonomic dysfunctions; Sensory, speech and swallowing problems; and Neuropsychiatric symptoms also related to statements outside their respective clusters. Clusters rated most important were Participation and Mobility and motor functioning, and the highest rated items were quality of life, walking ability, and sleeping problems.CONCLUSION:By the use of concept mapping, a multi-perspective conceptual map of prioritized aspects for the outcome measurement in PD was defined. These findings provide an initial conceptual basis toward improved outcome measurement priorities in clinical PD trials.
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| 19. |
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| 20. |
- Alcorta, M., et al.
(författare)
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Properties of resonances in 12C above the triple-alpha threshold
- 2011
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 312:SECTION 9, s. Art. no. 092013-
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Konferensbidrag (refereegranskat)abstract
- A complete kinematics study of the 10B(3He, pααα) and the 11B(3He, dααα) reactions has been performed to study the multi-particle break-up of 12C resonances above the triple-alpha threshold. The values of energy and widths of some states has been improved, and in states of natural parity partial branches of decay through the ground state of 8Be have been extracted. The influence of the "ghost" of the 8Be ground state has been taken into account in order to clarify the partial branches.
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| 21. |
- Aleksic, J., et al.
(författare)
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DETECTION OF VERY HIGH ENERGY gamma-RAY EMISSION FROM THE PERSEUS CLUSTER HEAD-TAIL GALAXY IC 310 BY THE MAGIC TELESCOPES
- 2010
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Ingår i: The Astrophysical Journal Letters. - 2041-8205. ; 723:2, s. l207-L212
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Tidskriftsartikel (refereegranskat)abstract
- We report on the detection with the MAGIC telescopes of very high energy (VHE) gamma-rays from IC 310, a head-tail radio galaxy in the Perseus galaxy cluster, observed during the interval 2008 November to 2010 February. The Fermi satellite has also detected this galaxy. The source is detected by MAGIC at a high statistical significance of 7.6 sigma in 20.6 hr of stereo data. The observed spectral energy distribution is flat with a differential spectral index of -2.00 +/- 0.14. The mean flux above 300 GeV, between 2009 October and 2010 February, (3.1 +/- 0.5) x 10(-12) cm(-2) s(-1), corresponds to (2.5 +/- 0.4)% of Crab Nebula units. Only an upper limit, of 1.9% of Crab Nebula units above 300 GeV, was obtained with the 2008 data. This, together with strong hints (>3 sigma) of flares in the middle of 2009 October and November, implies that the emission is variable. The MAGIC results favor a scenario with the VHE emission originating from the inner jet close to the central engine. More complicated models than a simple one-zone synchrotron self-Compton (SSC) scenario, e. g., multi-zone SSC, external Compton, or hadronic, may be required to explain the very flat spectrum and its extension over more than three orders of magnitude in energy.
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| 22. |
- Beecham, Ashley H, et al.
(författare)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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Tidskriftsartikel (refereegranskat)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 23. |
- Berthomier, M., et al.
(författare)
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Alfven : magnetosphere-ionosphere connection explorers
- 2012
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Ingår i: Experimental astronomy. - Dordrecht : Springer. - 0922-6435 .- 1572-9508. ; 33:2-3, s. 445-489
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Tidskriftsartikel (refereegranskat)abstract
- The aurorae are dynamic, luminous displays that grace the night skies of Earth's high latitude regions. The solar wind emanating from the Sun is their ultimate energy source, but the chain of plasma physical processes leading to auroral displays is complex. The special conditions at the interface between the solar wind-driven magnetosphere and the ionospheric environment at the top of Earth's atmosphere play a central role. In this Auroral Acceleration Region (AAR) persistent electric fields directed along the magnetic field accelerate magnetospheric electrons to the high energies needed to excite luminosity when they hit the atmosphere. The "ideal magnetohydrodynamics" description of space plasmas which is useful in much of the magnetosphere cannot be used to understand the AAR. The AAR has been studied by a small number of single spacecraft missions which revealed an environment rich in wave-particle interactions, plasma turbulence, and nonlinear acceleration processes, acting on a variety of spatio-temporal scales. The pioneering 4-spacecraft Cluster magnetospheric research mission is now fortuitously visiting the AAR, but its particle instruments are too slow to allow resolve many of the key plasma physics phenomena. The Alfv,n concept is designed specifically to take the next step in studying the aurora, by making the crucial high-time resolution, multi-scale measurements in the AAR, needed to address the key science questions of auroral plasma physics. The new knowledge that the mission will produce will find application in studies of the Sun, the processes that accelerate the solar wind and that produce aurora on other planets.
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| 24. |
- Campa, Daniele, et al.
(författare)
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Leukocyte telomere length in relation to pancreatic cancer risk: a prospective study.
- 2014
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755 .- 1055-9965. ; 23:11, s. 2447-2454
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several studies have examined leukocyte telomere length (LTL) as a possible predictor for cancer at various organ sites. The hypothesis originally motivating many of these studies was that shorter telomeres would be associated with an increase in cancer risk, the results of epidemiologic studies have been inconsistent, however, and suggested positive, negative, or null associations. Two studies have addressed the association of LTL in relation to pancreatic cancer risk and the results are contrasting. Methods: we measured LTL in a prospective study of 331 pancreatic cancer cases and 331 controls in the context of the European Prospective Investigation into Cancer and Nutrition (EPIC). Results: We observed that the mean LTL was higher in cases (0.59±0.20) than in controls (0.57±0.17), although this difference was not statistically significant (p=0.07), and a basic logistic regression model showed no association of LTL with pancreas cancer risk. When adjusting for levels of HbA1c and C-Peptide, however, there was a weakly positive association between longer LTL and pancreatic cancer risk , OR=1.13 (1.01-1.27). Additional analyses by cubic spline regression suggested a possible non-linear relationship between RTL and pancreatic cancer risk (P=0.022), with a statistically non-significant increase in risk at very low LTL, as well as a significant increase at high LTL. Conclusion: Taken together, the results from our study do not support LTL as a uniform and strong predictor of pancreatic cancer. Impact: The results of this manuscript can provide insights into telomere dynamics and highlight the complex relationship between LTL and pancreatic cancer risk.
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| 25. |
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| 26. |
- Gunell, H., et al.
(författare)
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Plasma penetration of the dayside magnetopause
- 2012
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Ingår i: Physics of Plasmas. - Melville, NY : AIP Publishing. - 1070-664X .- 1089-7674. ; 19:7, s. 072906-
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Tidskriftsartikel (refereegranskat)abstract
- Data from the Cluster spacecraft during their magnetopause crossing on 25 January 2002 are presented. The magnetopause was in a state of slow non-oscillatory motion during the observational period. Coherent structures of magnetosheath plasma, here typified as plasmoids, were seen on closed magnetic field lines on the inside of the magnetopause. Using simultaneous measurements on two spacecraft, the inward motion of the plasmoids is followed from one spacecraft to the next, and it is found to be in agreement with the measured ion velocity. The plasma characteristics and the direction of motion of the plasmoids show that they have penetrated the magnetopause, and the observations are consistent with the concept of impulsive penetration, as it is known from theory, simulations, and laboratory experiments. The mean flux across the magnetopause observed was 0.2%-0.5% of the solar wind flux at the time, and the peak values of the flux inside the plasmoids reached approximately 20% of the solar wind flux.
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| 27. |
- Gunell, H., et al.
(författare)
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Waves in high-speed plasmoids in the magnetosheath and at the magnetopause
- 2014
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Ingår i: Annales Geophysicae. - : Copernicus GmbH. - 0992-7689 .- 1432-0576. ; 32:8, s. 991-1009
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Tidskriftsartikel (refereegranskat)abstract
- Plasmoids, defined here as plasma entities with a higher anti-sunward velocity component than the surrounding plasma, have been observed in the magnetosheath in recent years. During the month of March 2007 the Cluster spacecraft crossed the magnetopause near the subsolar point 13 times. Plasmoids with larger velocities than the surrounding magnetosheath were found on seven of these 13 occasions. The plasmoids approach the magnetopause and interact with it. Both whistler mode waves and waves in the lower hybrid frequency range appear in these plasmoids, and the energy density of the waves inside the plasmoids is higher than the average wave energy density in the magnetosheath. When the spacecraft are in the magnetosphere, Alfvenic waves are observed. Cold ions of ionospheric origin are seen in connection with these waves, when the wave electric and magnetic fields combine with the Earth's dc magnetic field to yield an E x B/B-2 drift speed that is large enough to give the ions energies above the detection threshold.
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| 28. |
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| 29. |
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| 30. |
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| 31. |
- Hamrin, Maria, et al.
(författare)
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The evolution of flux pileup regions in the plasma sheet : Cluster observations
- 2013
-
Ingår i: Journal of Geophysical Research. - : American Geophysical Union (AGU). - 0148-0227 .- 2156-2202 .- 2169-9380 .- 2169-9402. ; 118:10, s. 6279-6290
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Tidskriftsartikel (refereegranskat)abstract
- Bursty bulk flows (BBFs) play an important role for the mass, energy, and magnetic flux transport in the plasma sheet, and the flow pattern in and around a BBF has important consequences for the localized energy conversion between the electromagnetic and plasma mechanical energy forms. The plasma flow signature in and around BBFs is often rather complicated. Return flows and plasma vortices are expected to exist at the flanks of the main flow channel, especially near the inner plasma sheet boundary, but also farther down-tail. A dipolarization front (DF) is often observed at the leading edge of a BBF, and a flux pileup region (FPR) behind the DF. Here we present Cluster data of three FPRs associated with vortex flows observed in the midtail plasma sheet on 15 August 2001. According to the principles of Fu et al. (2011, 2012c), two of the FPRs are considered to be in an early stage of evolution (growing FPRs). The third FPR is in a later stage of evolution (decaying FPR). For the first time, the detailed energy conversion properties during various stages of the FPR evolution have been measured. We show that the later stage FPR has a more complex vortex pattern than the two earlier stage FPRs. The two early stage FPR correspond to generators, EJ<0, while the later stage FPR only shows weak generator characteristics and is instead dominated by load signatures at the DF, EJ>0. Moreover, to our knowledge, this is one of the first times BBF-related plasma vortices have been observed to propagate over the spacecraft in the midtail plasma sheet at geocentric distances of about 18R(E). Our observations are compared to recent simulation results and previous observations.
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| 32. |
- Keiling, A., et al.
(författare)
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Magnetosphere-ionosphere coupling of global Pi2 pulsations
- 2014
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Ingår i: Journal of Geophysical Research A: Space Physics. - 2169-9380. ; 119:4, s. 2717-2739
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Tidskriftsartikel (refereegranskat)abstract
- Global Pi2 pulsations have mainly been associated with either low/middle latitudes or middle/high latitudes and, as a result, have been treated as two different types of Pi2 pulsations, either the plasmaspheric cavity resonance or the transient response of the substorm current wedge, respectively. However, in some reports, global Pi2 pulsations have a single period spanning low/middle/high latitudes. This super global type has not yet been satisfactorily explained. In particular, it has been a major challenge to identify the coupling between the source region and the ground. Here we report two consecutive super global Pi2 events which were observed over a wide latitudinal and longitudinal range. Using four spacecraft that were azimuthally spread out in the nightside and one spacecraft in the tail lobe, it was possible to follow the Pi2 signal along various paths with time delays from the magnetotail to the ground. Furthermore, it was found that the global pulsations were a combination of various modes including the transient Alfven and fast modes, field line resonance, and possibly a forced cavity-type resonance. As for the source of the Pi2 periodicity, oscillatory plasma flow inside the plasma sheet during flow braking (e.g., interchange oscillations) is a likely candidate. Such flow modulations, resembling the ground Pi2 pulsations, were recorded for both events.
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| 33. |
- Nakamura, R., et al.
(författare)
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Low- altitude electron acceleration due to multiple flow bursts in themagnetotail
- 2014
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 41:3, s. 777-784
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Tidskriftsartikel (refereegranskat)abstract
- At 10:00 UT on 25 February 2008, Cluster 1 spacecraft crossed the near-midnight auroral zone, at about 2R(E) altitude, while two of the Time History of Events and Macroscale Interactions During Substorms (THEMIS) spacecraft, THD and THE, observed multiple flow bursts on the near-conjugate plasma sheet field lines. The flow shear pattern at THEMIS was consistent with the vortical motion at duskside of a localized flow channel. Coinciding in time with the flow bursts, Cluster 1 observed bursts of counterstreaming electrons with mostly low energies (441eV), accompanied by short time scale (<5s) magnetic field disturbances embedded in flow-associated field-aligned current systems. This conjugate event not only confirms the idea that the plasma sheet flows are the driver of the kinetic Alfven waves accelerating the low-energy electrons but is a unique observation of disturbances in the high-altitude auroral region relevant to the multiple plasma sheet flows. Key Points First observation of multiple flow signatures on near-conjugate flux tubes Low-energy electron profile suggests Alfvenic acceleration due to fast flow Multiple flow bursts are obtained to extend over large radial distance in tail
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| 34. |
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| 35. |
- Nilsson, Maria H., et al.
(författare)
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Assessment of fall-related self-efficacy and activity avoidance in people with Parkinson's disease
- 2010
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Ingår i: BMC Geriatrics. - 1471-2318 .- 1471-2318. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Fear of falling (FOF) is common in Parkinson's disease (PD), and it is considered a vital aspect of comprehensive balance assessment in PD. FOF can be conceptualized differently. The Falls-Efficacy Scale (FES) assesses fall-related self-efficacy, whereas the Survey of Activities and Fear of Falling in the Elderly (SAFFE) assesses activity avoidance due to the risk of falling. This study aimed at investigating the validity and reliability of FES and SAFFE in people with PD.METHODS: Seventy-nine people with PD (mean age; 64 years, SD 7.2) completed the Swedish version of FES(S), SAFFE and the physical functioning (PF) scale of the 36-Item Short-Form Health Survey (SF-36). FES(S) and SAFFE were administered twice, with an 8.8 (SD 2.3) days interval. Assumptions for summing item scores into total scores were examined and score reliability (Cronbach's alpha and test-retest reliability) were calculated. Construct validity was assessed by examining the pattern of Spearman correlations (rs) between the FES(S)/SAFFE and other variables, and by examining differences in FES(S)/SAFFE scores between fallers and non-fallers, genders, and between those reporting FOF and unsteadiness while turning.RESULTS: For both scales, item mean scores (and standard deviations) were roughly similar and corrected item-total correlations exceeded 0.4. Reliabilities were ≥ 0.87. FES(S)-scores correlated strongest (rs, -0.74, p < 0.001) with SAFFE-scores, whereas SAFFE-scores correlated strongest with PF-scores (rs, -0.76, p < 0.001). Both scales correlated weakest with age (rs ≤ 0.08). Experiencing falls, unsteadiness while turning, and FOF was associated with lower fall-related self-efficacy and higher activity avoidance.CONCLUSIONS: This study provides initial support for the score reliability and validity of the FES(S) and SAFFE in people with PD.
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| 36. |
- Nilsson, Maria H, et al.
(författare)
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Housing and Health: Very Old People with Self-Reported Parkinson's Disease versus Controls.
- 2013
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Ingår i: Parkinson's Disease. - : Hindawi Limited. - 2042-0080 .- 2090-8083. ; 2013
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To explore whether aspects of housing and health among very old people with self-reported Parkinson's disease (PD) differ from matched controls. Methods. Data from the ENABLE-AGE Survey Study were used to identify people with self-reported PD (n = 20) and three matched controls/individual (n = 60). The matching criteria were age (mean = 82 years), sex, country, and type of housing. The analyses targeted problems in activities of daily living, objective and perceived aspects of housing, for example, number of environmental barriers, accessibility (i.e., person-environment fit), and usability. Results. The number of physical environmental barriers did not differ (P = 0.727) between the samples. The PD sample had more (P < 0.001) accessibility problems than controls and perceived their homes as less (P = 0.003) usable in relation to activities. They were less independent and had more functional limitations (median 5 versus 2; P < 0.001), and 70% experienced loss of stamina or poor balance. Conclusions. Due to the fact that they have more functional limitations than very old people in general, those with self-reported PD live in housing with more accessibility problems. This explorative study has implications for rehabilitation as well as societal planning, but larger studies including people with a confirmed PD diagnosis are needed.
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| 37. |
- Ohlsson, Claes, 1965, et al.
(författare)
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Genetic determinants of serum testosterone concentrations in men.
- 2011
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 7:10
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Tidskriftsartikel (refereegranskat)abstract
- Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n=871) and two de novo replication cohorts (n=4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG) locus (17p13-p12) were identified as independently associated with serum testosterone concentration (rs12150660, p=1.2×10(-41) and rs6258, p=2.3×10(-22)). Subjects with ≥ 3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p=5.6×10(-16)). The rs6258 polymorphism in exon 4 of SHBG affected SHBG's affinity for binding testosterone and the measured free testosterone fraction (p<0.01). Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation.
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| 38. |
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| 39. |
- Scuteri, Angelo, et al.
(författare)
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Arterial stiffness and influences of the metabolic syndrome: A cross-countries study.
- 2014
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 233:2, s. 654-660
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Tidskriftsartikel (refereegranskat)abstract
- Specific clusters of metabolic syndrome (MetS) components impact differentially on arterial stiffness, indexed as pulse wave velocity (PWV). Of note, in several population-based studies participating in the MARE (Metabolic syndrome and Arteries REsearch) Consortium the occurrence of specific clusters of MetS differed markedly across Europe and the US. The aim of the present study was to investigate whether specific clusters of MetS are consistently associated with stiffer arteries in different populations. We studied 20,570 subjects from 9 cohorts representing 8 different European countries and the US participating in the MARE Consortium. MetS was defined in accordance with NCEP ATPIII criteria as the simultaneous alteration in ≥3 of the 5 components: abdominal obesity (W), high triglycerides (T), low HDL cholesterol (H), elevated blood pressure (B), and elevated fasting glucose (G). PWV measured in each cohort was "normalized" to account for different acquisition methods. MetS had an overall prevalence of 24.2% (4985 subjects). MetS accelerated the age-associated increase in PWV levels at any age, and similarly in men and women. MetS clusters TBW, GBW, and GTBW are consistently associated with significantly stiffer arteries to an extent similar or greater than observed in subjects with alteration in all the five MetS components - even after controlling for age, sex, smoking, cholesterol levels, and diabetes mellitus - in all the MARE cohorts. In conclusion, different component clusters of MetS showed varying associations with arterial stiffness (PWV).
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| 40. |
- Skeppstedt, Maria, et al.
(författare)
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Automatic recognition of disorders, findings, pharmaceuticals and body structures from clinical text : An annotation and machine learning study
- 2014
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Ingår i: Journal of Biomedical Informatics. - : Elsevier BV. - 1532-0464 .- 1532-0480. ; 49, s. 148-158
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Tidskriftsartikel (refereegranskat)abstract
- Automatic recognition of clinical entities in the narrative text of health records is useful for constructing applications for documentation of patient care, as well as for secondary usage in the form of medical knowledge extraction. There are a number of named entity recognition studies on English clinical text, but less work has been carried out on clinical text in other languages. This study was performed on Swedish health records, and focused on four entities that are highly relevant for constructing a patient overview and for medical hypothesis generation, namely the entities: Disorder, Finding, Pharmaceutical Drug and Body Structure. The study had two aims: to explore how well named entity recognition methods previously applied to English clinical text perform on similar texts written in Swedish; and to evaluate whether it is meaningful to divide the more general category Medical Problem, which has been used in a number of previous studies, into the two more granular entities, Disorder and Finding. Clinical notes from a Swedish internal medicine emergency unit were annotated for the four selected entity categories, and the inter-annotator agreement between two pairs of annotators was measured, resulting in an average F-score of 0.79 for Disorder, 0.66 for Finding, 0.90 for Pharmaceutical Drug and 0.80 for Body Structure. A subset of the developed corpus was thereafter used for finding suitable features for training a conditional random fields model. Finally, a new model was trained on this subset, using the best features and settings, and its ability to generalise to held-out data was evaluated. This final model obtained an F-score of 0.81 for Disorder, 0.69 for Finding, 0.88 for Pharmaceutical Drug, 0.85 for Body Structure and 0.78 for the combined category Disorder + Finding. The obtained results, which are in line with or slightly lower than those for similar studies on English clinical text, many of them conducted using a larger training data set, show that the approaches used for English are also suitable for Swedish clinical text. However, a small proportion of the errors made by the model are less likely to occur in English text, showing that results might be improved by further tailoring the system to clinical Swedish. The entity recognition results for the individual entities Disorder and Finding show that it is meaningful to separate the general category Medical Problem into these two more granular entity types, e.g. for knowledge mining of co-morbidity relations and disorder-finding relations.
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| 41. |
- Sluijs, Ivonne, et al.
(författare)
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The amount and type of dairy product intake and incident type 2 diabetes : results from the EPIC-InterAct Study
- 2012
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 96:2, s. 382-390
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dairy product intake may be inversely associated with risk of type 2 diabetes, but the evidence is inconclusive for total dairy products and sparse for types of dairy products.Objective: The objective was to investigate the prospective association of total dairy products and different dairy subtypes with incidence of diabetes in populations with marked variation of intake of these food groups.Design: A nested case-cohort within 8 European countries of the European Prospective Investigation into Cancer and Nutrition Study (n = 340,234; 3.99 million person-years of follow-up) included a random subcohort (n = 16,835) and incident diabetes cases (n = 12,403). Baseline dairy product intake was assessed by using dietary questionnaires. Country-specific Prentice-weighted Cox regression HRs were calculated and pooled by using a random-effects meta-analysis.Results: Intake of total dairy products was not associated with diabetes (HR for the comparison of the highest with the lowest quintile of total dairy products: 1.01; 95% CI: 0.83, 1.34; P-trend = 0.92) in an analysis adjusted for age, sex, BMI, diabetes risk factors, education, and dietary factors. Of the dairy subtypes, cheese intake tended to have an inverse association with diabetes (HR: 0.88; 95% CI: 0.76, 1.02; P-trend = 0.01), and a higher combined intake of fermented dairy products (cheese, yogurt, and thick fermented milk) was inversely associated with diabetes (HR: 0.88; 95% CI: 0.78, 0.99; P-trend = 0.02) in adjusted analyses that compared extreme quintiles.Conclusions: This large prospective study found no association between total dairy product intake and diabetes risk. An inverse association of cheese intake and combined fermented dairy product intake with diabetes is suggested, which merits further study. Ant J Clin Nutr 2012;96:382-90.
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| 42. |
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| 43. |
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| 44. |
- Thordardottir, Björg, et al.
(författare)
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"You plan, but you never know" - participation among people with different levels of severity of Parkinson's disease.
- 2014
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Ingår i: Disability and Rehabilitation. - : Informa UK Limited. - 0963-8288 .- 1464-5165. ; 36:26, s. 2216-2224
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Purpose: The aim of this study was to improve our understanding of important aspects of participation in everyday life for people with different levels of severity of Parkinson's disease (PD). Methods: A qualitative design was used, with empirical data obtained from focus groups. The participants had all been diagnosed with PD at least one year prior to the start of the study. Purposeful sampling was used to ensure that both sexes, with variations in age, marital status, living arrangements, education and employment, were represented. Recruitment continued until saturation was reached and resulted in 29 participants. Homogeneity within each focus group was based on self-rated PD severity (mild, moderate or severe). Findings: The aspects that influence participation at different stages of PD are that those with PD stand out in public, as a result of disease-specific features, and that the disease is unpredictable. Planning was highlighted as a strategy that is required to support participation and cope with stress and to compensate for the fact that everyday activities demanded a great deal of time and energy. Conclusion: These findings are of importance to the development of rehabilitation interventions that support people with PD in maintaining their participation in everyday life, throughout the course of the disease. Implications for Rehabilitation PD severity and disease-specific problems (e.g. freezing of gait) need to be taken into account when tackling restrictions that affect participation. Interventions that aim to facilitate participation require different components and expertise depending on PD severity, as well as on individual preferences and needs. Structuring and planning everyday life might not facilitate participation for all those with PD, but concrete measures, such as making a schedule in order to structure daily life, may benefit those with milder PD.
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| 45. |
- Zamora-Ros, R., et al.
(författare)
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Flavonoid and lignan intake in relation to bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study
- 2014
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 111:9, s. 1870-1880
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is growing evidence of the protective role of dietary intake of flavonoids and lignans on cancer, but the association with bladder cancer has not been thoroughly investigated in epidemiological studies. We evaluated the association between dietary intakes of total and subclasses of flavonoids and lignans and risk of bladder cancer and its main morphological type, urothelial cell carcinoma (UCC), within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Methods: A cohort of 477 312 men and women mostly aged 35-70 years, were recruited in 10 European countries. At baseline, dietary flavonoid and lignan intakes were estimated using centre-specific validated questionnaires and a food composition database based on the Phenol-Explorer, the UK Food Standards Agency and the US Department of Agriculture databases. Results: During an average of 11 years of follow-up, 1575 new cases of primary bladder cancer were identified, of which 1425 were UCC (classified into aggressive (n = 430) and non-aggressive (n = 413) UCC). No association was found between total flavonoid intake and bladder cancer risk. Among flavonoid subclasses, significant inverse associations with bladder cancer risk were found for intakes of flavonol (hazard ratio comparing fifth with first quintile (HRQ5-Q1) 0.74, 95% confidence interval (CI): 0.61-0.91; P-trend = 0.009) and lignans (HRQ5-Q 10.78, 95% CI: 0.62-0.96; P-trend = 0.046). Similar results were observed for overall UCC and aggressive UCC, but not for non-aggressive UCC. Conclusions: Our study suggests an inverse association between the dietary intakes of flavonols and lignans and risk of bladder cancer, particularly aggressive UCC.
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| 46. |
- Allvin, Helen, et al.
(författare)
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Characteristics of Finnish and Swedish intensive care nursing narratives : a comparative analysis to support the development of clinical language technologies
- 2011
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Ingår i: Journal of Biomedical Semantics. - 2041-1480. ; 2:S1, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Free text is helpful for entering information into electronic health records, but reusing it is a challenge. The need for language technology for processing Finnish and Swedish healthcare text is therefore evident; however, Finnish and Swedish are linguistically very dissimilar. In this paper we present a comparison of characteristics in Finnish and Swedish free-text nursing narratives from intensive care. This creates a framework for characterising and comparing clinical text and lays the groundwork for developing clinical language technologies. Methods: Our material included daily nursing narratives from one intensive care unit in Finland and one in Sweden. Inclusion criteria for patients were an inpatient period of least five days and an age of at least 16 years. We performed a comparative analysis as part of a collaborative effort between Finnish- and Swedish-speaking healthcare and language technology professionals that included both qualitative and quantitative aspects. The qualitative analysis addressed the content and structure of three average- sized health records from each country. In the quantitative analysis 514 Finnish and 379 Swedish health records were studied using various language technology tools. Results: Although the two languages are not closely related, nursing narratives in Finland and Sweden had many properties in common. Both made use of specialised jargon and their content was very similar. However, many of these characteristics were challenging regarding development of language technology to support producing and using clinical documentation. Conclusions: The way Finnish and Swedish intensive care nursing was documented, was not country or language dependent, but shared a common context, principles and structural features and even similar vocabulary elements. Technology solutions are therefore likely to be applicable to a wider range of natural languages, but they need linguistic tailoring. Availability: The Finnish and Swedish data can be found at: http://www.dsv.su.se/ hexanord/data/
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| 47. |
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| 48. |
- Bladh, Stina, et al.
(författare)
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Psychometric performance of a generic walking scale (Walk-12G) in Multiple Sclerosis and Parkinson's disease
- 2012
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Ingår i: Journal of Neurology. - Heidelberg : Springer Berlin/Heidelberg. - 0340-5354 .- 1432-1459. ; 259:4, s. 729-738
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Tidskriftsartikel (refereegranskat)abstract
- Walking difficulties are common in neurological and other disorders, as well as among the elderly. There is a need for reliable and valid instruments for measuring walking difficulties in everyday life since existing gait tests are clinician rated and focus on situation specific capacity. The Walk-12G was adapted from the 12-item multiple sclerosis walking scale as a generic patient-reported rating scale for walking difficulties in everyday life. The aim of this study is to examine the psychometric properties of the Walk-12G in people with multiple sclerosis (MS) and Parkinson’s disease (PD). The Walk-12G was translated into Swedish and evaluated qualitatively among 25 people with and without various neurological and other conditions. Postal survey (MS, n = 199; PD, n = 189) and clinical (PD, n = 36) data were used to test its psychometric properties. Respondents considered the Walk-12G relevant and easy to use. Mean completion time was 3.5 min. Data completeness was good (<5% missing item responses) and tests of scaling assumptions supported summing item scores to a total score (corrected item-total correlations >0.6). Coefficient alpha and test–retest reliabilities were >0.9, and standard errors of measurement were 2.3–2.8. Construct validity was supported by correlations in accordance with a priori expectations. Results are similar to those with previous Walk-12G versions, indicating that scale adaptation was successful. Data suggest that the Walk-12G meets rating scale criteria for clinical trials, making it a valuable complement to available gait tests. Further studies involving other samples and application of modern psychometric methods are warranted to examine the scale in more detail.
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| 49. |
- Ekstam, Lisa, et al.
(författare)
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A research-based strategy for managing housing adaptations: study protocol for a quasi-experimental trial
- 2014
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Ingår i: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: The primary aim of this paper is to describe the design of a project evaluating the effects of using a research-based strategy for managing housing adaptations (HAs). The evaluation targets clients' perspectives in terms of activity, participation, usability, fear of falling, fall incidence, use of mobility devices, and health-related quality of life, and determines the societal effects of HAs in terms of costs. Additional aims of the project are to explore and describe this strategy in relation to experiences and expectations (a) among clients and cohabitants and (b) occupational therapists in ordinary practice. Methods/design: This study is a quasi-experimental trial applying a multiphase design, combining quantitative and qualitative data. At the experimental sites, the occupational therapists (OTs) apply the intervention, i.e. a standardized research-based strategy for HA case management. At the control site, the occupational therapists are following their regular routine in relation to HA. Three municipalities in south Sweden will be included based on their population, their geographical dispersion, and their similar organizational structures for HA administration. Identical data on outcomes is being collected at all the sites at the same four time points: before the HA and then 3, 6, and 12 months after the HA. The data-collection methods are semi-structured qualitative interviews, observations, clinical assessments, and certificates related to each client's HA. Primary outcomes are the usability of the home and the client's independence in daily activities (ADL). Cross-sectional and longitudinal data analyses will be conducted as well as statistical analyses, health-economic analyses, and qualitative analyses. Qualitative and quantitative data will be sequentially analyzed, and case studies will be developed. Discussion: The intervention in this study has been developed and tested through many years of research and in collaboration with practitioners. This process includes methodological development and testing research aimed at identifying the most important outcomes and research targeting current HA case-management procedures in Swedish municipalities. When the study is completed, the results will be used for further optimization of the practice strategy for HA, in close collaboration with the data-collecting OTs.
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| 50. |
- Fuks, Kateryna B., et al.
(författare)
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Arterial blood pressure and long-term exposure to traffic-related air pollution : an analysis in the European Study of Cohorts for Air Pollution Effects (ESCAPE)
- 2014
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Ingår i: Journal of Environmental Health Perspectives. - : National Institute of Environmental Health Sciences (NIEHS). - 0091-6765 .- 1552-9924. ; 122:9, s. 896-905
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Long-term exposure to air pollution is hypothesized to elevate arterial blood pressure (BP). The existing evidence is scarce and country-specific. OBJECTIVES: We investigated the cross-sectional association of long-term traffic-related air pollution with BP and prevalent hypertension in European populations. METHODS: Fifteen population-based cohorts, participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE), were analysed. Residential exposure to particulate matter and nitrogen oxides was modelled with land use regression using a uniform protocol. Traffic exposure was assessed with traffic indicator variables. We analysed systolic and diastolic BP in participants medicated and non-medicated with BP lowering medication (BPLM) separately, adjusting for personal and area-level risk factors and environmental noise. Prevalent hypertension was defined as ≥ 140 mmHg systolic, or ≥ 90 mmHg diastolic BP, or intake of BPLM. We combined cohort-specific results using random-effects meta-analysis. RESULTS: In the main meta-analysis of 113,926 participants, traffic load on major roads within 100 m of the residence was associated with increased systolic and diastolic BP in non-medicated participants (0.35 mmHg [95% CI: 0.02-0.68] and 0.22 mmHg [95% CI: 0.04-0.40] per 4,000,000 vehicles × m/day, respectively). The estimated odds ratio for prevalent hypertension was 1.05 [95% CI: 0.99-1.11] per 4,000,000 vehicles × m/day. Modelled air pollutants and BP were not clearly associated. CONCLUSIONS: In this first comprehensive meta-analysis of European population-based cohorts we observed a weak positive association of high residential traffic exposure with BP in non-medicated participants, and an elevated OR for prevalent hypertension. The relationship of modelled air pollutants with BP was inconsistent.
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