<p>Mediation analyses play a critical role in social and personality psychology research. However, current approaches for assessing power and sample size in mediation models have limitations, particularly when dealing with complex mediation models and multiple mediator sequential models. These limitations stem from limited software options and the substantial computational time required. In this part, we address these challenges by extending the joint significance test and product of coefficients test to incorporate the fourth-pathed mediated effect and generalized kth-pathed mediated effect. Additionally, we propose a model-based bootstrap method and provide convenient R tools for estimating power in complex mediation models. Through our research, we demonstrate that power decreases as the number of mediators increases and as the influence of coefficients varies. We summarize our results and discuss the implications of power analysis in relation to mediator complexity and coefficient influence. We provide insights for researchers seeking to optimize study designs and enhance the reliability of their findings in complex mediation models. </p> <p>Matching is a crucial step in causal inference, as it allows for more robust and reasonable analyses by creating better-matched pairs. However, in real-world scenarios, data are often collected and stored by different local institutions or separate departments, posing challenges for effective matching due to data fragmentation. Additionally, the harmonization of such data needs to prioritize privacy preservation. In this part, we propose a new hierarchical framework that addresses these challenges by implementing differential privacy on raw data to protect sensitive information while maintaining data utility. We also design a data access control system with three different access levels for designers based on their roles, ensuring secure and controlled access to the matched datasets. Simulation studies and analyses of datasets from the 2017 Atlantic Causal Inference Conference Data Challenge are conducted to showcase the flexibility and utility of our framework. Through this research, we contribute to the advancement of statistical methodologies in matching and privacy-preserving data analysis, offering a practical solution for data integration and privacy protection in causal inference studies. </p> <p>Biomarker discovery is a complex and resource-intensive process, encompassing discovery, qualification, verification, and validation stages prior to clinical evaluation. Streamlining this process by efficiently identifying relevant biomarkers in the discovery phase holds immense value. In this part, we present a likelihood ratio-based approach to accurately identify truly relevant protein markers in discovery studies. Leveraging the observation of unimodal underlying distributions of expression profiles for irrelevant markers, our method demonstrates promising performance when evaluated on real experimental data. Additionally, to address non-normal scenarios, we introduce a kernel ratio-based approach, which we evaluate using non-normal simulation settings. Through extensive simulations, we observe the high effectiveness of the kernel method in discovering the set of truly relevant markers, resulting in precise biomarker identifications with elevated sensitivity and a low empirical false discovery rate.  </p>

La toxicité potentielle des nanomatériaux présente un intérêt sociétal et scientifique élevé en raison de la promesse d'innovations pour de nombreuses applications techniques. Cependant, elle n’est pas forcément liée à la taille réelle, à la masse, à la surface des nanoparticules (NP) ou à leurs agglomérats. La toxicité des NPs pourrait être fortement influencée par d'autres propriétés inhérentes et encore incomprises telles que le relargage d’ions, de la particule elle-même, sa surface, ou des molécules adhérentes à la surface, qui interfèreraient avec l'absorption cellulaires des NPs. Le projet « NANOGAM» étroitement lié au projet « FNR CORE2012 NANION », vise à définir certains processus et facteurs impliqués dans l'absorption des NPs et leur toxicité. Une telle compréhension est une condition préalable au développement des nanomatériaux, fondement de la philosophie « safer-by-design ». Les objectifs de ce projet de thèse sont multiples. En tenant compte des caractéristiques des principaux paramètres physico-chimiques tels que la taille et l’aspect de la surface, l’étude a porté sur l'absorption de NPs d'argent et d'or, et leurs effets biologiques via une approche multi-biomarqueurs (mortalité, effets comportementaux, effets physiologiques, effets transcriptomiques, etc.) sur une espèce sensible, Gammarus fossarum (Crustacea Amphipoda). Le but de cette investigation est de comprendre si la toxicité des nanomatériaux est inhérente aux propriétés intrinsèques des NPs ou plutôt aux ions relargués, ce qui contribuera à la prédiction de la toxicité des NPs en rapport avec leurs propriétés physico-chimiques et ce afin de limiter le nombre d’essais répétitifs sur de nouveaux nanomatériaux. G. fossarum ont été exposés à de faibles concentrations d'AgNPs et AuNPs pendant 72h à jeun et 15 jours nourris. Les résultats obtenus ont montré que (i) la nature de l’enrobage de surface est le principal facteur responsable de l'absorption d'AgNPs et d'AuNPs par G. fossarum ; (ii) les ions libérés et les NPs elles-mêmes jouent un rôle dans la toxicité des AgNPs et AuNPs étudiées ; (iii) la composition chimique des NPs a conduit à des effets différents aux niveaux sub-individuels (transcriptomique), ainsi qu’à une distribution différente dans les tissues selon la nature métallique de la NP. Les AgNPs ont été localisées dans les branchies de G. fossarum tandis que les AuNPs ont été observées dans les caeca intestinaux. Cette étude a également révélé que Gammarus sp. est un excellent modèle pour l'étude de la toxicité et des effets des AgNPs et des AuNPs / The potential toxicity of nanomaterials is of high societal and scientific interest due to the promise of ground-breaking innovations for many technical applications. However, toxicity can often not be related to the actual size, mass or surface area of the single nanoparticles (NPs) or the NP agglomerates. Therefore, it can be proposed that the toxicity is greatly influenced by other inherent and non-understood properties of the particles to which ions dissolving from the particle, surface or molecules adhering to the surface interfering with the uptake of NPs into cells, may have important contributions. The PhD project “NANOGAM”, closely linked up to CORE2012 NANION project that aims to obtain knowledge to understand some of the processes and factors involved in NP uptake and toxicity as such understanding is a prerequisite for the development of nanomaterials following the safer-by-design philosophy. This PhD project aims to investigate, based on known characteristics of the key physico-chemical parameters; as size and surface functionalities, of a well-chosen list of silver and gold NPs, the uptake, and dependent biological effects of different complexity (mortality, behavioural effects, physiological effects, transcriptomic effects, etc.), on a sensitive species; Gammarus fossarum (Crustacea Amphipoda), in order to understand to which extent toxicity of nanomaterials is due to intrinsic material properties or ion leaching. Such understanding will contribute to the prediction of toxicity based on material properties rather than repetitive testing of an indefinite number of new nanomaterials. G. fossarum were exposed at low concentrations of AgNPs and AuNPs for 72h or 15 days in presence or absence of food. The obtained results showed that (i) surface coating is the main factor governing AgNPs and AuNPs uptake by G. fossarum, (ii) both released ions and NPs themselves play a role in the potency of the studied AgNPs and AuNPs and (iii) chemical composition led to different effects at the sub-individual levels (target genes expression) and different tissue distribution as AgNPs were found in G. fossarum gills while AuNPs were found in the intestinal caeca. Additionally, this work shows that Gammarus sp. are valuable models for the study of the effects of AgNPs and AuNPs