Modeling Outcome of Implantable Defibrillator Patients

Sudden cardiac arrest (SCA) is the sudden cessation of cardiac activity so that the victim becomes unresponsive, with no normal breathing and no signs of circulation. If corrective measures are not taken rapidly, this condition progresses to sudden cardiac death (SCD).1 Sudden cardiac death is caused by ventricular arrhythmias in the majority of cases. Implantable cardioverter-defibrillator (ICD) therapy has shown to be highly effective in terminating these life-threatening arrhythmias, but is associated with potentially severe complications and high costs. In this chapter, we review the current knowledge on the epidemiology, the etiology, and the preventive therapy of SCD. Also, the topic of costeffectiveness of ICD therapy is introduced

Height, social position and coronary heart disease incidence: the contribution of genetic and environmental factors

Background: The associations between height, socioeconomic position (SEP) and coronary heart disease (CHD) incidence are well established, but the contribution of genetic factors to these associations is still poorly understood. We used a polygenic score (PGS) for height to shed light on these associations. Methods: Finnish population-based health surveys in 1992-2011 (response rates 65-93%) were linked to population registers providing information on SEP and CHD incidence up to 2019. The participants (N=29 996; 54% women) were aged 25-75 at baseline, and there were 1767 CHD incident cases (32% in women) during 472 973 person years of follow-up. PGS-height was calculated based on 33 938 single-nucleotide polymorphisms, and residual height was defined as the residual of height after adjusting for PGS-height in a linear regression model. HRs of CHD incidence were calculated using Cox regression. Results: PGS-height and residual height showed clear gradients for education, social class and income, with a larger association for residual height. Residual height also showed larger associations with CHD incidence (HRs per 1 SD 0.94 in men and 0.87 in women) than PGS-height (HRs per 1 SD 0.99 and 0.97, respectively). Only a small proportion of the associations between SEP and CHD incidence was statistically explained by the height indicators (6% or less). Conclusions: Residual height associations with SEP and CHD incidence were larger than for PGS-height. This supports the role of material and social living conditions in childhood as contributing factors to the association of height with both SEP and CHD risk

Band gap reduction in GaNSb alloys due to the anion mismatch

The structural and optoelectronic properties in GaNxSb1–x alloys (0<=x<0.02) grown by molecular-beam epitaxy on both GaSb substrates and AlSb buffer layers on GaAs substrates are investigated. High-resolution x-ray diffraction (XRD) and reciprocal space mapping indicate that the GaNxSb1–x epilayers are of high crystalline quality and the alloy composition is found to be independent of substrate, for identical growth conditions. The band gap of the GaNSb alloys is found to decrease with increasing nitrogen content from absorption spectroscopy. Strain-induced band-gap shifts, Moss-Burstein effects, and band renormalization were ruled out by XRD and Hall measurements. The band-gap reduction is solely due to the substitution of dilute amounts of highly electronegative nitrogen for antimony, and is greater than observed in GaNAs with the same N content

Marital status and genetic liability independently predict coronary heart disease incidence

Aims: Married individuals have a lower coronary heart disease (CHD) risk than non-married, but the mechanisms behind this are not fully understood. We analyzed whether genetic liability to CHD may affect these associations. Methods: Marital status, a polygenic score of CHD (PGS-CHD), and other risk factors for CHD were measured from 35,444 participants (53% female) in Finnish population-based surveys conducted between 1992 and 2012. During the register-based follow-up until 2020, there were 2439 fatal and non-fatal incident CHD cases. The data were analyzed using linear and Cox regression models. Results: Divorced and cohabiting men and women had a higher genetic risk of CHD than married individuals, but the difference was very small (0.023–0.058 standard deviation of PGS-CHD, p-values 0.011–0.429). Both marital status and PGS-CHD were associated with CHD incidence, but the associations were largely independent. Adjusting for behavioral and metabolic risk factors for CHD explained part of these associations (11–20%). No interaction was found between marital status and PGS-CHD for CHD incidence. Conclusions: We showed minor differences between the marital status categories in PGS-CHD and demonstrated that marital status and genetic liability predicted CHD incidence largely independently. This emphasizes the need to measure multiple risk factors when predicting CHD risk

Estimation of causal effects of a time-varying exposure at multiple time points through multivariable mendelian randomization

Mendelian Randomisation (MR) is a powerful tool in epidemiology that can be used to estimate the causal effect of an exposure on an outcome in the presence of unobserved confounding, by utilising genetic variants as instrumental variables (IVs) for the exposure. The effect estimates obtained from MR studies are often interpreted as the lifetime effect of the exposure in question. However, the causal effects of some exposures are thought to vary throughout an individual’s lifetime with periods during which an exposure has a greater effect on a particular outcome. Multivariable MR (MVMR) is an extension of MR that allows for multiple, potentially highly related, exposures to be included in an MR estimation. MVMR estimates the direct effect of each exposure on the outcome conditional on all the other exposures included in the estimation. We explore the use of MVMR to estimate the direct effect of a single exposure at different time points in an individual’s lifetime on an outcome. We use simulations to illustrate the interpretation of the results from such analyses and the key assumptions required. We show that causal effects at different time periods can be estimated through MVMR when the association between the genetic variants used as instruments and the exposure measured at those time periods varies. However, this estimation will not necessarily identify exact time periods over which an exposure has the most effect on the outcome. Prior knowledge regarding the biological basis of exposure trajectories can help interpretation. We illustrate the method through estimation of the causal effects of childhood and adult BMI on C-Reactive protein and smoking behaviour

Saccade dysmetria indicates attenuated visual exploration in autism spectrum disorder

Background: Visual exploration in autism spectrum disorder (ASD) is characterized by attenuated social attention. The underlying oculomotor function during visual exploration is understudied, whereas oculomotor function during restricted viewing suggested saccade dysmetria in ASD by altered pontocerebellar motor modulation. Methods: Oculomotor function was recorded using remote eye tracking in 142 ASD participants and 142 matched neurotypical controls during free viewing of naturalistic videos with and without human content. The sample was heterogenous concerning age (6–30 years), cognitive ability (60–140 IQ), and male/female ratio (3:1). Oculomotor function was defined as saccade, fixation, and pupil‐dilation features that were compared between groups in linear mixed models. Oculomotor function was investigated as ASD classifier and features were correlated with clinical measures. Results: We observed decreased saccade duration (∆M = −0.50, CI [−0.21, −0.78]) and amplitude (∆M = −0.42, CI [−0.12, −0.72]), which was independent of human video content. We observed null findings concerning fixation and pupil‐dilation features (POWER = .81). Oculomotor function is a valid ASD classifier comparable to social attention concerning discriminative power. Within ASD, saccade features correlated with measures of restricted and repetitive behavior. Conclusions: We conclude saccade dysmetria as ASD oculomotor phenotype relevant to visual exploration. Decreased saccade amplitude and duration indicate spatially clustered fixations that attenuate visual exploration and emphasize endogenous over exogenous attention. We propose altered pontocerebellar motor modulation as underlying mechanism that contributes to atypical (oculo‐)motor coordination and attention function in ASD

Assortative mating and within-spouse pair comparisons

Spousal comparisons have been proposed as a design that can both reduce confounding and estimate effects of the shared adulthood environment. However, assortative mating, the process by which individuals select phenotypically (dis)similar mates, could distort associations when comparing spouses. We evaluated the use of spousal comparisons, as in the within-spouse pair (WSP) model, for aetiological research such as genetic association studies. We demonstrated that the WSP model can reduce confounding but may be susceptible to collider bias arising from conditioning on assorted spouse pairs. Analyses using UK Biobank spouse pairs found that WSP genetic association estimates were smaller than estimates from random pairs for height, educational attainment, and BMI variants. Within-sibling pair estimates, robust to demographic and parental effects, were also smaller than random pair estimates for height and educational attainment, but not for BMI. WSP models, like other within-family models, may reduce confounding from demographic factors in genetic association estimates, and so could be useful for triangulating evidence across study designs to assess the robustness of findings. However, WSP estimates should be interpreted with caution due to potential collider bias