Accelerated epigenetic aging in Werner syndrome.

Individuals suffering from Werner syndrome (WS) exhibit many clinical signs of accelerated aging. While the underlying constitutional mutation leads to accelerated rates of DNA damage, it is not yet known whether WS is also associated with an increased epigenetic age according to a DNA methylation based biomarker of aging (the "Epigenetic Clock"). Using whole blood methylation data from 18 WS cases and 18 age matched controls, we find that WS is associated with increased extrinsic epigenetic age acceleration (p=0.0072) and intrinsic epigenetic age acceleration (p=0.04), the latter of which is independent of age-related changes in the composition of peripheral blood cells. A multivariate model analysis reveals that WS is associated with an increase in DNA methylation age (on average 6.4 years, p=0.011) even after adjusting for chronological age, gender, and blood cell counts. Further, WS might be associated with a reduction in naïve CD8+ T cells (p=0.025) according to imputed measures of blood cell counts. Overall, this study shows that WS is associated with an increased epigenetic age of blood cells which is independent of changes in blood cell composition. The extent to which this alteration is a cause or effect of WS disease phenotypes remains unknown

Principles of model specification in ANOVA designs

ANOVA—the workhorse of experimental psychology—seems well understood in that behavioral sciences have agreed-upon contrasts and reporting conventions. Yet, we argue this consensus hides considerable flaws in common ANOVA procedures, and these flaws become especially salient in the within-subject and mixed-model cases. The main thesis is that these flaws are in model specification. The specifications underlying common use are deficient from a substantive perspective, that is, they do not match reality in behavioral experiments. The problem, in particular, is that specifications rely on coincidental rather than robust statements about reality. We provide specifications that avoid making arguments based on coincidences, and note these Bayes factor model comparisons among these specifications are already convenient in the BayesFactor package. Finally, we argue that model specification necessarily and critically reflects substantive concerns, and, consequently, is ultimately the responsibility of substantive researchers. Source code for this project is at github/PerceptionAndCognitionLab/stat_aov2

Early diagnosis of acute myocardial infarction in the elderly using more sensitive cardiac troponin assays

Aims To examine the diagnostic accuracy of sensitive cardiac troponin (cTn) assays in elderly patients, since elevated levels with sensitive cTn assays were reported in 20% of elderly patients without acute myocardial infarction (AMI). Methods and results In this multi-centre study, we included 1098 consecutive patients presenting with symptoms suggestive of AMI, 406 (37%) were >70 years old. Measurement of three investigational sensitive cTn assays [Roche high-sensitive cTnT (hs-cTnT), Siemens cTnI-Ultra, and Abbott-Architect cTnI) and the standard assay (Roche cTnT) was performed in a blinded fashion. The final diagnosis was adjudicated by two independent cardiologists. Acute myocardial infarction was the adjudicated final diagnosis in 24% of elderly patients. Among elderly patients without AMI, baseline cTn levels were elevated above the 99th percentile in 51% with Roche hs-cTnT, in 17% with Siemens TnI-Ultra, and 13% with Abbott-Architect cTnI. The diagnostic accuracy as quantified by the area under the receiver operating characteristic (ROC) curve (AUC) was significantly greater for the sensitive cTn assays compared with the standard assay (AUC for Roche hs-cTnT, 0.94; Siemens cTnI-Ultra, 0.95; and Abbott-Architect cTnI, 0.95 vs. AUC for the standard assay, 0.90; P < 0.05 for comparisons). The best cut-offs for the sensitive cTn-assays determined by the ROC-curve in elderly patients differed clearly from those in younger patients. Furthermore, the prognostic value regarding 90-day mortality varied among the sensitive cTn assays. Conclusion Sensitive cTn assays have high diagnostic accuracy also in the elderly. Mild elevations are common in elderly non-AMI patients, therefore the optimal cut-off levels are substantially higher in elderly as compared with younger patients. Furthermore, sensitive cTn assays yielded different prognostic value (ClinicalTrials.gov number, NCT00470587

Early diagnosis of acute myocardial infarction in patients with pre-existing coronary artery disease using more sensitive cardiac troponin assays

Aims We sought to examine the diagnostic and prognostic utility of sensitive cardiac troponin (cTn) assays in patients with pre-existing coronary artery disease (CAD). Methods and results We conducted a multicentre study to examine the diagnostic accuracy of one high-sensitive and two sensitive cTn assays in 1098 consecutive patients presenting with symptoms suggestive of acute myocardial infarction (AMI), of whom 401 (37%) had pre-existing CAD. Measurements of Roche high-sensitive cTnT (hs-cTnT), Siemens cTnI-Ultra, Abbott-Architect cTnI and the standard assay (Roche cTnT) were performed in a blinded fashion. The final diagnosis was adjudicated by two independent cardiologists. Acute myocardial infarction was the final diagnosis in 19% of CAD patients. Among patients with diagnoses other than AMI, baseline cTn levels were elevated above the 99th percentile with Roche hs-cTnT in 40%, with Siemens TnI-Ultra in 15%, and Abbott-Architect cTnI in 13% of them. In patients with pre-existing CAD, the diagnostic accuracy at presentation, quantified by the area under the receiver operator characteristic curve (AUC), was significantly greater for the sensitive cTn assays compared with the standard assay (AUC for Roche hs-cTnT, 0.92; Siemens cTnI-Ultra, 0.94; and Abbott-Architect cTnI, 0.93 vs. AUC for the standard assay, 0.87; P < 0.01 for all comparisons). Elevated levels of cTn measured with the sensitive assays predicted mortality irrespective of pre-existing CAD, age, sex, and cardiovascular risk factors. Conclusion Sensitive cTn assays have high-diagnostic accuracy also in CAD patients. Mild elevations are common in non-AMI patients and test-specific optimal cut-off levels tend to be higher in CAD patients than in patients without history of CAD. Sensitive cTn assays also retain prognostic value. (ClinicalTrials.gov number, NCT00470587

A creative destruction approach to replication: Implicit work and sex morality across cultures

How can we maximize what is learned from a replication study? In the creative destruction approach to replication, the original hypothesis is compared not only to the null hypothesis, but also to predictions derived from multiple alternative theoretical accounts of the phenomenon. To this end, new populations and measures are included in the design in addition to the original ones, to help determine which theory best accounts for the results across multiple key outcomes and contexts. The present pre-registered empirical project compared the Implicit Puritanism account of intuitive work and sex morality to theories positing regional, religious, and social class differences; explicit rather than implicit cultural differences in values; self-expression vs. survival values as a key cultural fault line; the general moralization of work; and false positive effects. Contradicting Implicit Puritanism's core theoretical claim of a distinct American work morality, a number of targeted findings replicated across multiple comparison cultures, whereas several failed to replicate in all samples and were identified as likely false positives. No support emerged for theories predicting regional variability and specific individual-differences moderators (religious affiliation, religiosity, and education level). Overall, the results provide evidence that work is intuitively moralized across cultures

2017 Research & Innovation Day Program

A one day showcase of applied research, social innovation, scholarship projects and activities.https://first.fanshawec.ca/cri_cripublications/1004/thumbnail.jp

The JASP guidelines for conducting and reporting a Bayesian analysis

Despite the increasing popularity of Bayesian inference in empirical research, few practical guidelines provide detailed recommendations for how to apply Bayesian procedures and interpret the results. Here we offer specific guidelines for four different stages of Bayesian statistical reasoning in a research setting: planning the analysis, executing the analysis, interpreting the results, and reporting the results. The guidelines for each stage are illustrated with a running example. Although the guidelines are geared towards analyses performed with the open-source statistical software JASP, most guidelines extend to Bayesian inference in general

2016 Research & Innovation Day Program

A one day showcase of applied research, social innovation, scholarship projects and activities.https://first.fanshawec.ca/cri_cripublications/1003/thumbnail.jp

Bayes factors for mixed models: A discussion

van Doorn et al. (2021) outlined various questions that arise when conducting Bayesian model comparison for mixed effects models. Seven response articles offered their own perspective on the preferred setup for mixed model comparison, on the most appropriate specification of prior distributions, and on the desirability of default recommendations. This article presents a round-table discussion that aims to clarify outstanding issues, explore common ground, and outline practical considerations for any researcher wishing to conduct a Bayesian mixed effects model comparison

2018 Research & Innovation Day Program

A one day showcase of applied research, social innovation, scholarship projects and activities.https://first.fanshawec.ca/cri_cripublications/1005/thumbnail.jp