| 1. |
- Kivimäki, M., et al.
(författare)
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Job strain as a risk factor for coronary heart disease : A collaborative meta-analysis of individual participant data
- 2012
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 380:9852, s. 1491-1497
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Tidskriftsartikel (refereegranskat)abstract
- Background Published work assessing psychosocial stress (job strain) as a risk factor for coronary heart disease is inconsistent and subject to publication bias and reverse causation bias. We analysed the relation between job strain and coronary heart disease with a meta-analysis of published and unpublished studies. Methods We used individual records from 13 European cohort studies (1985-2006) of men and women without coronary heart disease who were employed at time of baseline assessment. We measured job strain with questions from validated job-content and demand-control questionnaires. We extracted data in two stages such that acquisition and harmonisation of job strain measure and covariables occurred before linkage to records for coronary heart disease. We defined incident coronary heart disease as the first non-fatal myocardial infarction or coronary death. Findings 30 214 (15%) of 197 473 participants reported job strain. In 1•49 million person-years at risk (mean follow-up 7•5 years [SD 1•7]), we recorded 2358 events of incident coronary heart disease. After adjustment for sex and age, the hazard ratio for job strain versus no job strain was 1•23 (95% CI 1•10-1•37). This effect estimate was higher in published (1•43, 1•15-1•77) than unpublished (1•16, 1•02-1•32) studies. Hazard ratios were likewise raised in analyses addressing reverse causality by exclusion of events of coronary heart disease that occurred in the first 3 years (1•31, 1•15-1•48) and 5 years (1•30, 1•13-1•50) of follow-up. We noted an association between job strain and coronary heart disease for sex, age groups, socioeconomic strata, and region, and after adjustments for socioeconomic status, and lifestyle and conventional risk factors. The population attributable risk for job strain was 3•4%. Interpretation Our findings suggest that prevention of workplace stress might decrease disease incidence; however, this strategy would have a much smaller effect than would tackling of standard risk factors, such as smoking. Funding Finnish Work Environment Fund, the Academy of Finland, the Swedish Research Council for Working Life and Social Research, the German Social Accident Insurance, the Danish National Research Centre for the Working Environment, the BUPA Foundation, the Ministry of Social Affairs and Employment, the Medical Research Council, the Wellcome Trust, and the US National Institutes of Health.
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| 2. |
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| 3. |
- Kaldmäe, Margit, et al.
(författare)
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A “spindle and thread” mechanism unblocks p53 translation by modulating N-terminal disorder
- 2022
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Ingår i: Structure. - : Elsevier BV. - 0969-2126 .- 1878-4186. ; 30:5, s. 733-742, e1-e7
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Tidskriftsartikel (refereegranskat)abstract
- Disordered proteins pose a major challenge to structural biology. A prominent example is the tumor suppressor p53, whose low expression levels and poor conformational stability hamper the development of cancer therapeutics. All these characteristics make it a prime example of “life on the edge of solubility.” Here, we investigate whether these features can be modulated by fusing the protein to a highly soluble spider silk domain (NT∗). The chimeric protein displays highly efficient translation and is fully active in human cancer cells. Biophysical characterization reveals a compact conformation, with the disordered transactivation domain of p53 wrapped around the NT∗ domain. We conclude that interactions with NT∗ help to unblock translation of the proline-rich disordered region of p53. Expression of partially disordered cancer targets is similarly enhanced by NT∗. In summary, we demonstrate that inducing co-translational folding via a molecular “spindle and thread” mechanism unblocks protein translation in vitro.
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| 4. |
- Kivimäki, Mika, et al.
(författare)
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Cognitive stimulation in the workplace, plasma proteins, and risk of dementia : three analyses of population cohort studies
- 2021
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Ingår i: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833. ; 374
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To examine the association between cognitively stimulating work and subsequent risk of dementia and to identify protein pathways for this association.DESIGN: Multicohort study with three sets of analyses.SETTING: United Kingdom, Europe, and the United States.PARTICIPANTS: Three associations were examined: cognitive stimulation and dementia risk in 107 896 participants from seven population based prospective cohort studies from the IPD-Work consortium (individual participant data meta-analysis in working populations); cognitive stimulation and proteins in a random sample of 2261 participants from one cohort study; and proteins and dementia risk in 13 656 participants from two cohort studies.MAIN OUTCOME MEASURES: Cognitive stimulation was measured at baseline using standard questionnaire instruments on active versus passive jobs and at baseline and over time using a job exposure matrix indicator. 4953 proteins in plasma samples were scanned. Follow-up of incident dementia varied between 13.7 to 30.1 years depending on the cohort. People with dementia were identified through linked electronic health records and repeated clinical examinations.RESULTS: During 1.8 million person years at risk, 1143 people with dementia were recorded. The risk of dementia was found to be lower for participants with high compared with low cognitive stimulation at work (crude incidence of dementia per 10 000 person years 4.8 in the high stimulation group and 7.3 in the low stimulation group, age and sex adjusted hazard ratio 0.77, 95% confidence interval 0.65 to 0.92, heterogeneity in cohort specific estimates I2=0%, P=0.99). This association was robust to additional adjustment for education, risk factors for dementia in adulthood (smoking, heavy alcohol consumption, physical inactivity, job strain, obesity, hypertension, and prevalent diabetes at baseline), and cardiometabolic diseases (diabetes, coronary heart disease, stroke) before dementia diagnosis (fully adjusted hazard ratio 0.82, 95% confidence interval 0.68 to 0.98). The risk of dementia was also observed during the first 10 years of follow-up (hazard ratio 0.60, 95% confidence interval 0.37 to 0.95) and from year 10 onwards (0.79, 0.66 to 0.95) and replicated using a repeated job exposure matrix indicator of cognitive stimulation (hazard ratio per 1 standard deviation increase 0.77, 95% confidence interval 0.69 to 0.86). In analysis controlling for multiple testing, higher cognitive stimulation at work was associated with lower levels of proteins that inhibit central nervous system axonogenesis and synaptogenesis: slit homologue 2 (SLIT2, fully adjusted β -0.34, P<0.001), carbohydrate sulfotransferase 12 (CHSTC, fully adjusted β -0.33, P<0.001), and peptidyl-glycine α-amidating monooxygenase (AMD, fully adjusted β -0.32, P<0.001). These proteins were associated with increased dementia risk, with the fully adjusted hazard ratio per 1 SD being 1.16 (95% confidence interval 1.05 to 1.28) for SLIT2, 1.13 (1.00 to 1.27) for CHSTC, and 1.04 (0.97 to 1.13) for AMD.CONCLUSIONS: The risk of dementia in old age was found to be lower in people with cognitively stimulating jobs than in those with non-stimulating jobs. The findings that cognitive stimulation is associated with lower levels of plasma proteins that potentially inhibit axonogenesis and synaptogenesis and increase the risk of dementia might provide clues to underlying biological mechanisms.
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| 5. |
- Laakso, S.V.A., et al.
(författare)
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Dull punch line is not a joke – Worn cutting edge causes higher iron losses in electrical steel piercing
- 2018
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Ingår i: Robotics and Computer-Integrated Manufacturing. - : Elsevier BV. - 0736-5845.
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Tidskriftsartikel (refereegranskat)abstract
- © 2018 Elsevier Ltd Electrical steel is used for the active parts in electrical machinery that form the magnetic circuits because the material experiences low iron loss, and thus, has superior magnetizing properties. A typical electrical sheet has a thickness of 0.5 mm and is punched into its final shape via a piercing process. Piercing causes large deformations and residual stresses in the narrow zone of the cut surface. The deformations and stresses weaken the magnetic properties of the electrical sheet and result in additional losses, as the iron loss increases after piercing [1]. This paper presents a simulation model of the piercing process to evaluate the deformations and stresses on the cut surface. The model is constructed using the commercial FEM solver Deform. There has been an attempt to simulate the magneto-mechanical state of the punched surfaces, but the piercing process itself was not simulated [2] . The electrical steel sheet investigated in this paper is isotropic electrical silicon steel M400-50A (EN 10106-96).
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| 7. |
- Fransson, Eleonor I, et al.
(författare)
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Job strain and the risk of stroke : an individual-participant data meta-analysis
- 2015
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Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 46:2, s. 557-559
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Psychosocial stress at work has been proposed to be a risk factor for cardiovascular disease. However, its role as a risk factor for stroke is uncertain.METHODS: We conducted an individual-participant-data meta-analysis of 196 380 males and females from 14 European cohort studies to investigate the association between job strain, a measure of work-related stress, and incident stroke.RESULTS: In 1.8 million person-years at risk (mean follow-up 9.2 years), 2023 first-time stroke events were recorded. The age- and sex-adjusted hazard ratio for job strain relative to no job strain was 1.24 (95% confidence interval, 1.05;1.47) for ischemic stroke, 1.01 (95% confidence interval, 0.75;1.36) for hemorrhagic stroke, and 1.09 (95% confidence interval, 0.94;1.26) for overall stroke. The association with ischemic stroke was robust to further adjustment for socioeconomic status.CONCLUSION: Job strain may be associated with an increased risk of ischemic stroke, but further research is needed to determine whether interventions targeting job strain would reduce stroke risk beyond existing preventive strategies.
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| 8. |
- Fransson, Eleonor, 1971-, et al.
(författare)
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Job strain as a risk factor for leisure-time physical inactivity : an individual-participant meta-analysis of up to 170,000 men and women
- 2012
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Ingår i: American Journal of Epidemiology. - Cary : Oxford University Press. - 0002-9262 .- 1476-6256. ; 176:12, s. 1078-1089
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Forskningsöversikt (refereegranskat)abstract
- Unfavorable work characteristics, such as low job control and too high or too low job demands, have been suggested to increase the likelihood of physical inactivity during leisure time, but this has not been verified in large-scale studies. The authors combined individual-level data from 14 European cohort studies (baseline years from 19851988 to 20062008) to examine the association between unfavorable work characteristics and leisure-time physical inactivity in a total of 170,162 employees (50 women; mean age, 43.5 years). Of these employees, 56,735 were reexamined after 29 years. In cross-sectional analyses, the odds for physical inactivity were 26 higher (odds ratio 1.26, 95 confidence interval: 1.15, 1.38) for employees with high-strain jobs (low control/high demands) and 21 higher (odds ratio 1.21, 95 confidence interval: 1.11, 1.31) for those with passive jobs (low control/low demands) compared with employees in low-strain jobs (high control/low demands). In prospective analyses restricted to physically active participants, the odds of becoming physically inactive during follow-up were 21 and 20 higher for those with high-strain (odds ratio 1.21, 95 confidence interval: 1.11, 1.32) and passive (odds ratio 1.20, 95 confidence interval: 1.11, 1.30) jobs at baseline. These data suggest that unfavorable work characteristics may have a spillover effect on leisure-time physical activity.
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| 9. |
- Grassi, Lorenzo, et al.
(författare)
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Experimental Validation Of Finite Element Model For Proximal Composite Femur Using Optical Measurements
- 2013
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Ingår i: Journal of the Mechanical Behavior of Biomedical Materials. - : Elsevier BV. - 1751-6161. ; 21, s. 86-94
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Tidskriftsartikel (refereegranskat)abstract
- Patient-specific finite element models have been used to predict femur strength and fracture risk in individuals. Validation of the adopted finite element modelling procedure against mechanical testing data is a crucial step when aiming for clinical applications. The majority of the works available in literature used data from strain gages to validate the model, thus having up to 15 experimental measurements. Optical techniques, such as Digital Image Correlation, can help to improve the models by providing a continuous field of deformation data over a femoral surface. The main objective of this study was to validate finite element models of six composite femora against strain data from digital image correlation, obtained during fracture tests performed in quasi-axial loading configuration. The finite element models were obtained from CT scans, by means of a semi-automatic segmentation. The principal strains both during the elastic phase and close to the fracture were compared, and showed a correlation coefficient close to 0.9. In the linear region, the slope and intercept were close to zero and unity, while for the case when fracture load was simulated, the slope decreased somewhat. The accuracy of the obtained results is comparable with the state-of-the-art literature, with the significant improvement of having around 50000 data points for each femur. This large number of measurements allows a more comprehensive validation of the predictions by the finite element models, since thousand of points are tracked along the femoral neck and trochanter region, i.e., the sites that are most critical for femur fracture. Moreover, strain measurement biases due to the strain gage reinforcement effect, were avoided. The combined experimental-numerical approach proved to be ready for application to in-vitro tests of human cadaver femurs, thus helping to develop a suitable mechanistic fracture risk criterion.
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| 10. |
- Grassi, Lorenzo, et al.
(författare)
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Full-field Strain Measurement During Mechanical Testing of the Human Femur at Physiologically Relevant Strain Rates
- 2014
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Ingår i: Journal of Biomechanical Engineering. - : ASME International. - 0148-0731 .- 1528-8951. ; 136:11
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the mechanical properties of human femora is of great importance for the development of a reliable fracture criterion aimed at assessing fracture risk. Earlier ex vivo studies have been conducted by measuring strains on a limited set of locations using strain gauges. Digital Image Correlation (DIC) could instead be used to reconstruct the full-field strain pattern over the surface of the femur. The objective of this study was to measure the full-field strain response of cadaver femora tested at a physiological strain rate up to fracture in a configuration resembling single stance. The three cadaver femora were cleaned from soft tissues, and a white background paint was applied with a random black speckle pattern over the anterior surface. The mechanical tests were conducted up to fracture at a constant displacement rate of 15 mm/s, and two cameras recorded the event at 3000 frames per second. DIC was performed to retrieve the full-field displacement map, from which strains were derived. A low-pass filter was applied over the measured displacements before the crack opened in order to reduce the noise level. The noise levels were assessed using a dedicated control plate. Conversely, no filtering was applied at the frames close to fracture to get the maximum resolution. The specimens showed a linear behavior of the principal strains with respect to the applied force up to fracture. The strain rate was comparable to the values available in literature from in-vivo measurements during daily activities. The cracks opened and fully propagated in less than 1 ms, and small regions with high values of the major principal strains could be spotted just a few frames before the crack opened. This corroborates the hypothesis of a strain-driven fracture mechanism in human bone. The data represents a comprehensive collection of full-field strains, both at physiological load levels and up to fracture. About 10000 measurements were collected for each bone, providing superior spatial resolution compared to ~15 measurements typically collected using strain gauges. These experimental data collection can be further used for validation of numerical models, and for experimental verification of bone constitutive laws and fracture criteria.
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