A methodology for global validation of microarray experiments

BACKGROUND: DNA microarrays are popular tools for measuring gene expression of biological samples. This ever increasing popularity is ensuring that a large number of microarray studies are conducted, many of which with data publicly available for mining by other investigators. Under most circumstances, validation of differential expression of genes is performed on a gene to gene basis. Thus, it is not possible to generalize validation results to the remaining majority of non-validated genes or to evaluate the overall quality of these studies. RESULTS: We present an approach for the global validation of DNA microarray experiments that will allow researchers to evaluate the general quality of their experiment and to extrapolate validation results of a subset of genes to the remaining non-validated genes. We illustrate why the popular strategy of selecting only the most differentially expressed genes for validation generally fails as a global validation strategy and propose random-stratified sampling as a better gene selection method. We also illustrate shortcomings of often-used validation indices such as overlap of significant effects and the correlation coefficient and recommend the concordance correlation coefficient (CCC) as an alternative. CONCLUSION: We provide recommendations that will enhance validity checks of microarray experiments while minimizing the need to run a large number of labour-intensive individual validation assays

Body Composition (DXA) and Maximal Strength of Powerlifters: a Descriptive Quantitative and Longitudinal Study

International Journal of Exercise Science 16(4): 828-845, 2023. The purpose of this study was to present the relationships between maximal strength and body composition and to conduct yearly follow-ups presenting the chronic effects of maximal strength training on body composition. Thirty-four (age = 28.8 ± 8.7 yrs) classic powerlifters (M = 21; F = 13) completed at least one Dual-Energy X-Ray Absorptiometry (DXA) 43.97 ± 23.93 days after a sanctioned international powerlifting federation affiliate competition (Squat + Bench Press + Deadlift = Total (kg)). In addition, thirteen subjects (n = 13) completed at least one yearly follow up. Paired sample T-Tests and simple linear regressions were performed to determine significant effects on body composition and maximal strength measures. Prediction formulas were obtained as follows: Bone Mineral Content (BMC) (g) = 3.39 * Total (kg) + 1494.78 (r = 0.84; p \u3c 0.000; SEE = 348.05); Bone Mineral Density (BMD) (g/cm3) = 0.000390 * Total (kg) + 1.115 (r = 0.71; p \u3c 0.000; SEE = 0.062); Total (kg) = 10.84 * Lean Body Weight (LBW) (kg) – 154.89 (r = 0.90; p \u3c 0.000; SEE = 70.27); Total (kg) = 22.74 * Relative LBW (kg/m) – 306.66 (r = 0.92; p \u3c 0.000; SEE = 64.07). Significant differences were observed in BMD (+1.57 ± 1.55%; p = 0.018; ES = 0.22), between measures one and two (333.7 ± 36.3 days apart) as well as LBW (-2.95 ± 3.82%; p = 0.049; ES = 0.16), and Body Fat Percentage (+2.59%; p = 0.029; ES = 0.20) between measures two and three (336 ± 13.3 days apart). Thus, maximal strength can be used to predict BMC and BMD, while LBW can be used to predict maximal strength. As well, consistent powerlifting practice can increase BMD in adults

It is time to talk about people: a human-centered healthcare system

Examining vulnerabilities within our current healthcare system we propose borrowing two tools from the fields of engineering and design: a) Reason's system approach [1] and b) User-centered design [2,3]. Both approaches are human-centered in that they consider common patterns of human behavior when analyzing systems to identify problems and generate solutions. This paper examines these two human-centered approaches in the context of healthcare. We argue that maintaining a human-centered orientation in clinical care, research, training, and governance is critical to the evolution of an effective and sustainable healthcare system

Amyloid and tau pathology associations with personality traits, neuropsychiatric symptoms, and cognitive lifestyle in the preclinical phases of sporadic and autosomal dominant Alzheimer’s disease

Background Major prevention trials for Alzheimer’s disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In 2 cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle (years of education or lifetime cognitive activity) related to the pathological hallmarks of AD, amyloid-β, and tau deposits. Methods A total of 115 older adults with a parental or multiple-sibling family history of sporadic AD (PREVENT-AD [PRe-symptomatic EValuation of Experimental or Novel Treatments for AD] cohort) underwent amyloid and tau positron emission tomography and answered several questionnaires related to behavioral attributes. Separately, we studied 117 mutation carriers from the DIAN (Dominant Inherited Alzheimer Network) study group cohort with amyloid positron emission tomography and behavioral data. Using partial least squares analysis, we identified latent variables relating amyloid or tau pathology with combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle. Results In PREVENT-AD, lower neuroticism, neuropsychiatric burden, and higher education were associated with less amyloid deposition (p = .014). Lower neuroticism and neuropsychiatric features, along with higher measures of openness and extraversion, were related to less tau deposition (p = .006). In DIAN, lower neuropsychiatric burden and higher education were also associated with less amyloid (p = .005). The combination of these factors accounted for up to 14% of AD pathology. Conclusions In the preclinical phase of both sporadic and autosomal dominant AD, multiple behavioral features were associated with AD pathology. These results may suggest potential pathways by which multidomain interventions might help delay AD onset or progression

Characterization of eIF4E-interacting partners from Drosophila melanogaster

Numerical notation systems are structured, visual, and primarily non-phonetic systems for representing number. This study employs a diachronic and comparative framework to examine over 100 systems used during the past 5000 years. The historical context of each system's origin, transmission, transformation, and decline is traced, linking systems together into phylogenies, but according priority to neither analogical or homological explanations. Structural aspects of numerical notation systems are compared and the limits of variability among them are established. A two-dimensional typology is presented that analyzes the intraexponential and interexponential structuring of each system, in addition to one or more numerical bases. In previous approaches, the only relevant factor considered was the presence or absence of positionality, which led inevitably to unilinear and progressivist conclusions. The analysis of historical relations among numerical notation systems permits a direct approach to questions of how and why they changed. The application of a multilinear cultural evolutionary framework reveals both synchronic and diachronic regularities among numerical notation systems. Where possible, these cross-cultural regularities are related to principles of cognitive psychology. Full explanations of the cultural evolution of numerical notation must also take account of social factors because changes in systems are always the product of decisions made in particular social contexts. Most numerical notation systems are used only for recording and communication, not computation, so it is illegitimate to evaluate their usefulness for functions for which they were never used. A model is presented that relates structural features of numerical notation systems to the contexts of their use and transmission. Because positional systems are most useful for functions related to administrative and scientific institutions that promote cultural hegemony, the observed trend towards positional numerals is a consequence of the dominance of societies that possess such institutions rather than the numerals' inherent superiority

The Drosophila Poly(A) Binding Protein-Interacting Protein, dPaip2, Is a Novel Effector of Cell Growth

The 3′ poly(A) tail of eukaryotic mRNAs and the poly(A) binding protein (PABP) play important roles in the regulation of translation. Recently, a human PABP-interacting protein, Paip2, which disrupts the PABP-poly(A) interaction and consequently inhibits translation, was described. To gain insight into the biological role of Paip2, we studied the Drosophila melanogaster Paip2 (dPaip2). dPaip2 is the bona fide human Paip2 homologue, as it interacts with dPABP, inhibits binding of dPABP to the mRNA poly(A) tail, and reduces translation of a reporter mRNA by ∼80% in an S2 cell-free translation extract. Ectopic overexpression of dPaip2 in Drosophila wings and wing discs results in a size reduction phenotype, which is due to a decrease in cell number. Clones of cells overexpressing dPaip2 in wing discs also contain fewer cells than controls. This phenotype can be explained by a primary effect on cell growth. Indeed, overexpression of dPaip2 in postreplicative tissues inhibits growth, inasmuch as it reduces ommatidia size in eyes and cell size in the larval fat body. We conclude that dPaip2 inhibits cell growth primarily by inhibiting protein synthesis