ABSTRACT
BACKGROUND: The apolipoprotein E (APOE) É4 allele is reported to be a strong genetic risk factor for mild cognitive impairment (MCI) and Alzheimer's disease (AD). Additional genetic loci have been detected that influence the risk for late-onset AD. As socioeconomic position (SEP) is also strongly related to cognitive decline, SEP has been suggested to be a possible modifier of the genetic effect on MCI. OBJECTIVE: To investigate whether APOEÉ4 and a genetic sum score of AD-associated risk alleles (GRSAD) interact with SEP indicators to affect MCI in a population-based cohort. METHODS: Using data of 3,834 participants of the Heinz Nixdorf Recall Study, APOEÉ4 and GRSAD by SEP interactions were assessed using logistic regression models, as well as SEP-stratified genetic association analysis. Interaction on additive scale was calculated using the relative excess risk due to interaction (RERI). All analysis were additionally stratified by sex. RESULTS: Indication for interaction on the additive scale was found between APOEÉ4 and low education on MCI (RERI: 0.52 [95% confidence interval (CI): 0.01; 1.03]). The strongest genetic effects of the APOEÉ4 genotype on MCI were observed in groups of low education (Odds ratio (OR): 1.46 [95% CI: 0.79; 2.63] for≤10 years of education versus OR: 1.00 [95% CI: 0.43; 2.14] for≥18 years of education). Sex stratified results showed stronger effects in women. No indication for interaction between the GRSAD and SEP indicators on MCI was observed. CONCLUSION: Results indicate that low education may have an impact on APOEÉ4 expression on MCI, especially among women.
Subject(s)
Alzheimer Disease/genetics , Apolipoprotein E4/genetics , Cognitive Dysfunction/genetics , Socioeconomic Factors , Alleles , Cohort Studies , Female , Genotype , Humans , Male , Middle Aged , Risk Factors , Sex FactorsABSTRACT
The welding of aluminium high pressure die castings is a well known and broadly investigated challenge in various fields of industry and research. Prior research in this specific field mainly focused on the optimisation of the welding and the casting process and on the cause of the frequently occurring porosity and incomplete fusion phenomena, whereas the impacts of these defects have hardly been addressed. Therefore, the underlying study presents the investigation of weldments in EN AC-AlSi10MnMg high pressure aluminium die castings by linear elastic finite element analysis based on X-ray computed tomography as a novel approach. Hereby, four laser weldments with differing surfaces and pore contents were investigated by X-ray computed tomography and tensile testing. Based on the voxel datasets of the porous weldments, triangular finite element meshes were generated and a numerical finite element analysis was conducted. Good agreement of the stress-strain curves between the simulations and the experiments was achieved.
ABSTRACT
From the viewpoint of mechanics, weld cracking tends to occur if the induced tensile stress surpasses a certain value for the particular materials and the welding processes. Welding residual stresses (WRS) can be profoundly affected by the restraint conditions of the welded structures. For estimating the tendency of weld cracking, the small-scale H-type slit joints have been widely used for cracking tests. However, it is still hard to decide whether the real large-scale component can also be welded without cracking even though the tested weld cracking specimens on the laboratory scale can be welded without cracking. In this study, the intensity of restraint which quantitatively indicates how much a joint is restrained is used. The influence of restraint condition (intensity of restraint) on WRS is systematically investigated using both the numerical simulation and the experimental method. The achievement obtained in the current work is very beneficial to design effective H-type self-restrained cracking test specimens for evaluating the sensitivity of the material and the welding procedures for weld cracking in the real large-scale components.
