Facteur de confusion | EPFL Graph Search

En statistique, un facteur de confusion, ou facteur confondant, ou encore variable confondante, est une variable aléatoire qui influence à la fois la variable dépendante et les variables explicatives. Ces facteurs sont notamment à l'origine de la différence entre corrélation et causalité (Cum hoc ergo propter hoc). En santé publique, c'est une variable liée à la fois au facteur de risque et à la maladie ou à un autre évènement de l'étude lié à la santé, ce qui est susceptible d'induire un biais dans l'analyse du lien (entre maladie et facteur de risque), produisant ainsi de fausses associations. Rechercher et prendre en compte les facteurs de confusion est essentiel dans le cadre d'une étude épidémiologique. Par exemple, il y a corrélation entre la consommation de viande et le cancer du côlon ; mais l'obésité et le tabagisme sont également liés à la consommation de viande et ont une influence directe sur le cancer, et sont donc des facteurs de confusion qui rendent difficile la re

Mitochondrial stress signalling and its impacts on physiology

Adrienne Joëlle Laurence Mottis

Mitochondria are responsible for respiration and energy harvesting across the eukaryotic kingdom. They also take part in other cellular processes like intermediary metabolism. As a result, mitochondrial function directly impacts organismal features such as metabolic homeostasis, fitness and aging. Moreover, mitochondrial dysfunction is involved in numerous pathologies, such as neurodegenerative disease, obesity, diabetes and cancer. Several surveillance pathways constantly monitor mitochondria to ensure their proper function. Among the pathways triggered by stress, the mitochondrial unfolded protein response (UPRmt) aims to restore proteostasis within this organelle. A better understanding of the cellular response to mitochondrial stress would expand our fundamental knowledge of physiological and pathological processes involving mitochondria, leading to potential new therapeutics that target these organelles. This thesis focuses on the mechanistic and physiological characterization of the mitochondrial stress response in several organisms. I used the model organism Caenorhabtis elegans to screen for novel players of the UPRmt and found the poly(A)-binding protein pab-1. Using transcript profiling, we showed that the induction of immune genes is a common consequence of several mitochondrial stressors. We demonstrated that pab-1 regulates the activation of the mitochondrial stress response and innate immunity as well. On top, pab-1 is required for the survival of C. elegans upon bacterial infection. Transcriptomic data from multiple human tissues suggest that the human pab-1 orthologue, PABPC1, has a conserved role in immunity. In mice, I explored the regulation of the mitochondrial stress response using a combination of bioinformatics and in vivo experimental approaches. Combined transcriptomic and proteomic analyses in the BXD mouse genetic reference population revealed a tight co-regulation of the orthologues of the UPRmt under normal physiological conditions. As a complementary approach, we triggered mitochondrial stress pharmacologically in newly born and adult mice. Due to the bacterial ancestry of mitochondria, the effects of the antibiotic doxycycline (dox) are also deleterious to this organelle. We found that dox impairs mitochondrial proteostasis and oxygen consumption in adult mice. However, mitochondrial stress induced by post-natal dox treatment did not cause long-lasting effects on mouse physiology and longevity, which is very distinct from observations in C. elegans. The mammalian gut flora plays an important role in organismal homeostasis. The use of an antibiotic causes perturbations of the microbiota, with repercussions on metabolism, inflammation, and the nervous system. To eliminate these confounding effects, we also treated germ-free mice with dox to characterize the response of the mouse to a so-called âpureâ mitochondrial stress. Using multi-omics profiling, we found that organs highly dependent on mitochondria display specific transcriptomic and proteomic signatures following dox treatment. In the kidney, we observed an inhibition of translation and of the mTOR pathway, accompanied by an activation of the ATF4 integrated stress response (ISR). In the liver, dox led to a remodelling of lipid metabolism. In both organs, target transcripts of type I interferon anti-viral response were induced. This thesis demonstrates that the response to mitochondrial stress is a multi-faceted process with conserved aspects acr

EPFL2018

Brain Perfusion Measurements Using Multidelay Arterial Spin-Labeling Are Systematically Biased by the Number of Delays

Nicolas Gninenko, Sven Haller, Dimitri Nestor Alice Van De Ville, Merel Margaretha van der Thiel

BACKGROUND AND PURPOSE:Multidelay arterial spin-labeling is a promising emerging method in clinical practice. The effect of imaging parameters in multidelay arterial spin-labeling on estimated cerebral blood flow measurements remains unknown. We directly compared 3-delay versus 7-delay sequences, assessing the difference in the estimated transit time and blood flow. MATERIALS AND METHODS:This study included 87 cognitively healthy controls (78.7 3.8 years of age; 49 women). We assessed delay and transit time-uncorrected and transit time-corrected CBF maps. Data analysis included voxelwise permutation-based between-sequence comparisons of 3-delay versus 7-delay, within-sequence comparison of transit time-uncorrected versus transit time-corrected maps, and average CBF calculations in regions that have been shown to differ. RESULTS:The 7-delay sequence estimated a higher CBF value than the 3-delay for the transit time-uncorrected and transit time-corrected maps in regions corresponding to the watershed areas (transit time-uncorrected = 27.62 +/- 12.23 versus 24.58 +/- 11.70 mL/min/100 g, Cohen's d = 0.25; transit time-corrected = 33.48 +/- 14.92 versus 30.16 +/- 14.32 mL/min/100 g, Cohen's d = 0.23). In the peripheral regions of the brain, the estimated delay was found to be longer for the 3-delay sequence (1.52408 +/- 0.25236 seconds versus 1.47755 +/- 0.24242 seconds, Cohen's d = 0.19), while the inverse was found in the center of the brain (1.39388 +/- 0.22056 seconds versus 1.42565 +/- 0.21872 seconds, Cohen's d = 0.14). Moreover, 7-delay had lower hemispheric asymmetry. CONCLUSIONS:The results of this study support the necessity of standardizing acquisition parameters in multidelay arterial spin-labeling and identifying basic parameters as a confounding factor in CBF quantification studies. Our findings conclude that multidelay arterial spin-labeling sequences with a high number of delays estimate higher CBF values than those with a lower number of delays.

AMER SOC NEURORADIOLOGY2018

How to detect and reduce potential sources of biases in studies of SARS-CoV-2 and COVID-19

Mats Julius Stensrud

In response to the coronavirus disease (COVID-19) pandemic, public health scientists have produced a large and rapidly expanding body of literature that aims to answer critical questions, such as the proportion of the population in a geographic area that has been infected; the transmissibility of the virus and factors associated with high infectiousness or susceptibility to infection; which groups are the most at risk of infection, morbidity and mortality; and the degree to which antibodies confer protection to re-infection. Observational studies are subject to a number of different biases, including confounding, selection bias, and measurement error, that may threaten their validity or influence the interpretation of their results. To assist in the critical evaluation of a vast body of literature and contribute to future study design, we outline and propose solutions to biases that can occur across different categories of observational studies of COVID-19. We consider potential biases that could occur in five categories of studies: (1) cross-sectional seroprevalence, (2) longitudinal seroprotection, (3) risk factor studies to inform interventions, (4) studies to estimate the secondary attack rate, and (5) studies that use secondary attack rates to make inferences about infectiousness and susceptibility.

2021