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Sökning: WFRF:(Ing Alex)

  • Resultat 1-4 av 4
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1.
  • Andersson, Lena, et al. (författare)
  • Estimating trends in quartz exposure in Swedish iron foundries : predicting past and present exposures
  • 2012
  • Ingår i: Annals of Occupational Hygiene. - Oxford, United Kingdom : Oxford University Press. - 0003-4878 .- 1475-3162. ; 56:3, s. 362-372
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Swedish foundries have a long tradition of legally required surveys in the work place that, from the late 1960s onwards, included measurements of quartz. The availability of exposure data spanning almost 40 years presents a unique opportunity to study trends over that time and to evaluate the validity of exposure models based on data from shorter time spans. The aims of this study were (i) to investigate long term trends in quartz exposure over time, (ii) using routinely collected quartz exposure measurements to develop a mathematical model that could predict both historical and current exposure patterns, and (iii) to validate this exposure model with up-to-date measurements from a targeted survey of the industry.Methods: Eleven foundries, representative of the Swedish iron foundry industry, were divided into three groups based on the size of the companies, i.e. the number of employees. A database containing 2333 quartz exposure measurements for 11 different job descriptionswas used to create three models that covered time periods which reflected different work conditions and production processes: a historical model (1968– 1989), a development model (1990–2004), and a validation model (2005–2006). A linear mixed model for repeated measurements was used to investigate trends over time. In all mixed models, time period, company size, and job title were included as fixed (categorical) determinants of exposure. The within- and between-worker variances were considered to be random effects. A linear regression analysis was erformed to investigate agreement between the models. The average exposure was estimated for each combination of job title and company size.Results: A large reduction in exposure (51%) was seen between 1968 and 1974 and between 1975 and 1979 (28%). In later periods, quartz exposure was reduced by 8% per 5 years at best. In the first period, employees at smaller companies experienced ~50%higher exposure levels than those at large companies, but these differences became much smaller in later years. The furnace and ladle repair job were associated with the highest exposure, with 3.9–8.0 times the average exposure compared to the lowest exposed group. Without adjusting for this autonomous trend over time, predicting early historical exposures using our development model resulted in a statistically significant regression coefficient of 2.42 (R2 5 0.81), indicating an underestimation of historical exposure levels. Similar patterns were seen for other historical time periods. Comparing our development model with our validation model resulted in a statistically significant regression coefficient of 0.31, indicating an overestimation of current exposure levels.Conclusion: To investigate long-term trends in quartz exposure over time, overall linear trends can be determined by using mixed model analysis. To create individual exposure measures to predict historical exposures, it is necessary to consider factors such as the time period, type of job, type of company, and company size. The mixed model analysis showed systematic changes in concentration levels, implying that extrapolation of exposure estimates outside the range of years covered by measurements may result in underestimation or overestimation of exposure.
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2.
  • Meng, Weida, et al. (författare)
  • Genotype-dependent epigenetic regulation of DLGAP2 in alcohol use and dependence
  • 2021
  • Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:8, s. 4367-4382
  • Tidskriftsartikel (refereegranskat)abstract
    • Alcohol misuse is a major public health problem originating from genetic and environmental risk factors. Alterations in the brain epigenome may orchestrate changes in gene expression that lead to alcohol misuse and dependence. Through epigenome-wide association analysis of DNA methylation from human brain tissues, we identified a differentially methylated region, DMR-DLGAP2, associated with alcohol dependence. Methylation within DMR-DLGAP2 was found to be genotype-dependent, allele-specific and associated with reward processing in brain. Methylation at the DMR-DLGAP2 regulated expression of DLGAP2 in vitro, and Dlgap2-deficient mice showed reduced alcohol consumption compared with wild-type controls. These results suggest that DLGAP2 may be an interface for genetic and epigenetic factors controlling alcohol use and dependence.
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3.
  • Ramb, Rebecca, et al. (författare)
  • The impact of latent confounders in directed network analysis in neuroscience
  • 2013
  • Ingår i: Philosophical Transactions. Series A. - : Royal Society. - 1364-503X .- 1471-2962. ; 371:1997
  • Tidskriftsartikel (refereegranskat)abstract
    • In the analysis of neuroscience data, the identification of task-related causal relationships between various areas of the brain gives insights about the network of physiological pathways that are active during the task. One increasingly used approach to identify causal connectivity uses the concept of Granger causality that exploits predictability of activity in one region by past activity in other regions of the brain. Owing to the complexity of the data, selecting components for the analysis of causality as a preprocessing step has to be performed. This includes predetermined-and often arbitrary-exclusion of information. Therefore, the system is confounded by latent sources. In this paper, the effect of latent confounders is demonstrated, and paths of influence among three components are studied. While methods for analysing Granger causality are commonly based on linear vector autoregressive models, the effects of latent confounders are expected to be present also in nonlinear systems. Therefore, all analyses are also performed for a simulated nonlinear system and discussed with regard to applications in neuroscience.
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4.
  • Tay, Nicole, et al. (författare)
  • Allele-Specific Methylation of SPDEF : A Novel Moderator of Psychosocial Stress and Substance Abuse
  • 2019
  • Ingår i: American Journal of Psychiatry. - : AMER PSYCHIATRIC PUBLISHING, INC. - 0002-953X .- 1535-7228. ; 176:2, s. 146-155
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Psychosocial stress is a key risk factor for substance abuse among adolescents. Recently, epigenetic processes such as DNA methylation have emerged as potential mechanisms that could mediate this relationship. The authors conducted a genome-wide methylation analysis to investigate whether differentially methylated regions are associated with psychosocial stress in an adolescent population.Methods: A methylome-wide analysis of differentially methylated regions was used to examine a sample of 1,287 14-year-old adolescents (50.7% of them female) from the European IMAGEN study. The Illumina 450k array was used to assess DNA methylation, pyrosequencing was used for technical replication, and linear regression analyses were used to identify associations with psychosocial stress and substance use (alcohol and tobacco). Findings were replicated by pyrosequencing a test sample of 413 participants from the IMAGEN study.Results: Hypermethylation in the sterile alpha motif/pointed domain containing the ETS transcription factor (SPDEF) gene locus was associated with a greater number of stressful life events in an allele-dependent way. Among individuals with the minor G-allele, SPDEF methylation moderated the association between psychosocial stress and substance abuse. SPDEF methylation interacted with lifetime stress in gray matter volume in the right cuneus, which in turn was associated with the frequency of alcohol and tobacco use. SPDEF was involved in the regulation of trans-genes linked to substance use.Conclusions: Taken together, the study findings describe a novel epigenetic mechanism that helps explain how psychosocial stress exposure influences adolescent substance abuse.
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