L’objectif principal de la thèse était d’étudier les effets de l’alimentation et de l’obésité sur l’asthme et son évolution, en prenant en compte des facteurs de médiations spécifiques.La première partie de la thèse visait à étudier le rôle de l’alimentation dans l'asthme, en prenant en compte l’indice de masse corporelle (IMC) comme un médiateur potentiel, et en évaluant l’effet modificateur du tabac dans ces associations. Ce travail a d’abord porté sur le rôle de la consommation de charcuterie, récemment classée cancérogène. Parmi 971 adultes de l’étude des facteurs génétiques et environnementaux de l’asthme (EGEA), nous avons montré qu’une consommation élevée de charcuterie (au moins 4 fois par semaine) était associée de façon directe à l’aggravation des symptômes de l’asthme, et que seulement 14% de l’association entre la consommation de charcuterie et l’asthme était expliqué par l’IMC (effet indirect). Ce travail a ensuite porté sur le rôle de la qualité globale de l’alimentation, évaluée par le score alimentaire Alternate Healthy Eating Index 2010. Parmi 969 participants d’EGEA, nous avons montré qu’une alimentation de qualité était associée de façon directe à une amélioration des symptômes de l’asthme chez les non-fumeurs. L’effet indirect lié à l’IMC n’était pas significatif. La deuxième partie de la thèse visait à mieux comprendre l'association entre l'obésité et l'activité de l’asthme, en prenant en compte la leptine, une adipokine pro-inflammatoire, comme un médiateur potentiel. Parmi 331 adultes d’EGEA avec un asthme actif à l’inclusion, les analyses ont montré que différentes mesures élevées de la composition corporelle étaient associées à une activité persistante de l’asthme, avec un effet indirect très fort de la leptine dans ces associations. / The general aim of the thesis was to study the role of diet and obesity in asthma, while accounting for potential mediators in these analyses.The first part of the thesis aimed to investigate the role of dietary factors in asthma at a “macro-level”, considering body mass index (BMI) as a potential mediator, and to evaluate effect modification by smoking. We first focused on processed meat intake, a recent carcinogen. Among 971 participants from the Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA), analysis showed that high processed meat intake (at least 4 servings/week) was associated with worsening asthma symptoms over time, through a direct effect and to a lesser extent an effect mediated by BMI. We then focused on the overall diet quality assessed by the Alternate Healthy Eating Index 2010. Among 969 participants from the EGEA study, the analyses showed that a greater adherence to a better diet quality was associated with improved asthma symptoms over time in never smokers only and was not mediated through BMI. The second part of the thesis aimed to better understand the association between obesity and asthma at a “micro-level”, considering leptin, an inflammatory biological marker related to obesity, as a mediator. Including 331 participants from the EGEA study with current asthma at baseline, analysis showed that high body adiposity estimated by different measures was associated with persistent asthma activity, likely mediated by leptin.

In recent decades, more and more countries have opened up to international trade and the effects it has on society is an area that is both studied and discussed to a large extent, without reaching consensus. Understanding the full consequences of trade is important in order to make political decisions and create fair trade agreements. Previously, trade and gender inequality’s impact on poverty have been studied as two separate areas and in previous research we have not found studies examining the relationship between trade, poverty and gender inequality together. The purpose of this study is therefore to combine two areas that have previously been treated separately and to examine how international trade affects poverty and the role of gender inequality in the tiger economies. Tiger economies is a collective name for the rapidly growing economies of Asia and the countries are characterized by liberalized markets and openness to free trade. The study is carried out through a mediation analysis and examines whether inequality between the sexes acts as a mediator in the context of how trade affects poverty. For the estimation, panel data for eight countries over 30 years are used. The dependent variable poverty is measured as household consumption per capita, while trade flow and gender inequality and four other control variables are explanatory variables. The results show that both increased trade and higher gender equality lead to increased household consumption and thus reduced poverty in the tiger economies. The study also shows that gender inequality acts as a mediator for the relationship between trade and poverty, which means that trade leads to a reduction in poverty directly, but also that trade leads to increased female participation in the labor market, which in turn reduces poverty. Gender inequality and trade should therefore be studied together to examine the effect and the exclusion of one of the variables may lead to incorrect conclusions about what affects poverty in the tiger economies. / De senaste decennierna har allt fler länder öppnat upp för internationell handel och vilka effekter det har för samhället är ett område som både studeras och diskuteras i stor utsträckning, utan att nå konsensus. Att förstå de fulla konsekvenserna av handel är av betydelse för att kunna fatta politiska beslut och skapa rättvisa handelsavtal. Tidigare har handelns och ojämlikhet mellan könens påverkan på fattigdom studerats som två separata områden och vi har i den tidigare forskningen inte funnit studier som undersöker sambandet mellan handel, fattigdom och ojämlikhet mellan könen tillsammans. Syftet med denna studie är därför att kombinera två områden som tidigare behandlats separat och undersöka hur internationell handel påverkar fattigdom och vilken roll ojämlikhet mellan könen har i tigerekonomierna. Tigerekonomierna är ett samlingsnamn för snabbt växande ekonomier i Asien och länderna kännetecknas av avreglerade marknader och öppenhet mot frihandel. Studien genomförs genom en medieringsanalys och undersöker om ojämlikhet mellan könen fungerar som mediator i sambandet för hur handel påverkar fattigdom. För skattningen används paneldata för åtta länder över 30 år. Beroende variabeln fattigdom mäts som hushållskonumstion per capita, medan handelsflöde och ojämlikhet mellan könen samt fyra kontrollvariabler utgör förklarande variabler. Resultatet visar att både ökad handel och högre jämlikhet mellan könen leder till ökad hushållskonsumtion och således minskad fattigdom i tigerekonomierna. Studien visar även att ojämlikhet mellan könen fungerar som mediator för sambandet mellan handel och fattigdom, vilket innebär att handel dels leder till minskad fattigdom direkt, men även att handel leder till ökat kvinnligt deltagande på arbetsmarknaden som i sin tur minskar fattigdom. Ojämlikhet mellan könen och handel bör således studeras tillsammans för att undersöka effekten av hur de påverkar fattigdom och uteslutning av en av variablerna kan leda till felaktiga slutsatser om vad som påverkar fattigdom i tigerekonomierna.

The cause and effect paradigm underlying medical research has led to an enhanced etiological understanding of many diseases and the development of many lifesaving drugs, but the paradigm does not always include an understanding of the pathways involved. Causal mediation analysis extends the cause and effect relationship to the cause and effect through a mediator, an intermediate variable on the causal pathway. The total effect of an exposure on an outcome is decomposed into two parts: 1) the indirect effect of the exposure on the outcome through the mediator and 2) the direct effect of the exposure on the outcome through all other pathways. In this dissertation, I describe various counterfactual causal mediation frameworks with identifiability assumptions that all lead to the Mediation Formula. The indirect and direct effects can be estimated from observable data using a semi-parametric algorithm derived from the Mediation Formula that I generalize to different types of mediators and outcomes. With an increased interest in causal mediation analysis, thoughtful consideration is necessary in the application of the Mediation Formula to real-world data challenges. Here, I consider three motivating causal mediation questions in the areas of HIV curative research and cardio-respiratory fitness. HIV curative treatments typically target the viral reservoir, cells infected with latent HIV. Quantifying the effect of an HIV curative treatment on viral rebound over a set time horizon mediated by reductions in the viral reservoir can inform future directions for improving curative treatments. In cardiorespiratory fitness research, metabolites, molecules involved with cellular respiration, are believed to mediate the effect of physical activity on cardiorespiratory fitness. I propose three novel adaptations to the semi-parametric estimation algorithm to address three data challenges: 1) Numerical integration and optimization of the observed data likelihood for mediators with an assay lower limit (left-censored mediators); 2) Pseudo-value approach for time-to-event outcomes on a restricted mean survival time scale; 3) Elastic net regression for high-dimensional mediators. My novel approaches provide estimation frameworks that can be applied to a broad spectrum of research questions. I provide simulation studies to assess the properties of the estimators and applications of the methodologies to the motivating data. / 2025-06-16T00:00:00Z

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Många ungdomar spelar datorspel dagligen och trots att många spelar för underhållnings skull finns det dem som utvecklar problem likt missbruksproblematik. Datorspelsberoende är ingen diagnos men ingår i Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) som ett potentiellt nytt tillstånd som kräver ytterligare forskning. Föreliggande studie syftade till att undersöka vilka personlighetsdrag hos ungdomar som har ett samband med datorspelsberoende och som i sin tur har ett samband med psykisk ohälsa samt hur sambanden ser ut hos pojkar respektive flickor. Studiens övergripande syfte var att bidra med kunskap inom datorspelsberoende för att behandling för denna målgrupp ska kunna bli mer individanpassad. 123 gymnasieelever deltog i en enkätundersökning. Mediationsanalyser gjordes på datamaterialet, som bestod av specifika personlighetsdrag som prediktorvariabel, datorspelsberoende som mediator och psykisk ohälsa som utfallsvariabel. Inga mediationseffekter för det totala stickprovet uppmättes. Resultatet visade på tre medelstora mediationseffekter för pojkar och för flickor visades inget samband mellan prediktor-, mediator- och utfallsvariabel, varpå mediationsanalys inte utfördes på detta stickprov. Studiens resultat indikerar på att det finns en mediationseffekt av datorspelsberoende på relationen mellan specifika personlighetsdrag och psykisk ohälsa hos pojkar, men inte flickor. / Many adolescents play computer games daily and despite the fact that many play for the sake of entertainment, there are those who develop problems similar to addiction problems. Internet gaming addiction is not a diagnosis but it's part of Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) as a potentially new state that requires further research. This study aimed to investigate which personality traits of young people that have a relationship with Internet gaming addiction and which in turn have a relationship with mental illness and how the relationships between the variables interact in samples with boys and girls. The overall aim of the study was to contribute knowledge in Internet gaming addiction to enable treatment for this target group to become a more individualized treatment. 123 high school students participated in a survey. Mediation analysis were made on the data consisting of specific personality traits as predictor variable, Internet gaming addiction as mediator and mental illness as outcome variable. No mediation effects for the total sample were measured. The results showed 3 medium mediation effects for boys and for girls there was no correlation between predictor, mediator and outcome variables, after which mediation analysis was not performed on this sample. The results of the study indicate that there is a mediation effect of Internet gaming addiction on the relationship between specific personality traits and mental illness for boys, but not girls.

La nutrition est un facteur de risque modifiable pour le cancer puisqu'environ un tiers des cas pourraient être évités en adoptant une meilleure alimentation. La relation entre nutrition et cancer est complexe, et son étude est enrichie par de nouveaux défis apportés par les récentes avancées technologiques dans le domaine des « -omiques ». Cette thèse a pour but de développer de nouvelles approches biostatistiques afin d'étudier la relation entre nutrition et cancer au sein de la cohorte EPIC. Pour ce faire, l'applicabilité de nouvelles méthodologies multivariées dans le domaine de l'épidémiologie nutritionnelle a été étudiée.Une nouvelle méthode multivariée pour la réduction de la dimensionnalité, le Treelet Transform (TT), a été examinée afin d'extraire des patterns de nutriments issus de questionnaires. Les patterns ainsi obtenus par le TT étaient plus facilement interprétables que par les méthodes classiques. Ensuite, un cadre analytique pour implémenter le concept du « meeting-in-the-middle » (MITM) a été développé et appliqué dans 2 études cas-témoin nichées sur le cancer hépatocellulaire avec des données métabolomiques. Le MITM cherche à identifier des biomarqueurs qui soient à la fois des marqueurs de certaines expositions passées et des prédicteurs de maladies. L'implémentation s'est focalisée sur l'application de la PLS et de l'analyse de médiation.Enfin, nous avons examinés la relation entre les niveaux plasmatiques de 60 acides gras issus de biomarqueurs et le risque de cancer du sein dans une étude cas-témoin nichée dans EPIC.Cette thèse servira de base pour des applications épidémiologiques futures examinant la relation nutrition-cancer / Diet is a modifiable risk factor for many cancers. It has been estimated that about a third of cancer cases can be prevented by complying with a healthy diet and adhering to the recommendations in terms of nutrition. The nutrition-cancer relationship is a complex one, and its study is currently at a turning point with the opportunity and challenges brought by the recent technological advances in the fields of « -omics ».This thesis aims to develop new biostatistical approaches to investigate the nutrition-cancer relation within the European Prospective Investigation into Cancer and nutrition (EPIC) study. To do so, the applicability of new methodologies in the field of nutritional epidemiology has been examined.First, a new multivariate dimension reduction method, the Treelet Transform (TT) was applied to extract nutrient patterns relying on questionnaire data. The extracted patterns were more easily interpretable than those obtained with more classical methods.Then, an analytical framework was conceived for the « meeting-in-the-middle » (MITM) principle and applied to two nested case-control studies on hepatocellular carcinoma, with targeted and untargeted metabolomics data. The MITM aims to identify overlap biomarkers of certain exposures that are at the same time predictive of disease outcomes. The implementation focused on the application of partial least squares and mediation analyses. Last, the association between 60 plasma fatty acids levels assessed from biomarkers and breast cancer risk was examined in a nested case-control study in EPIC. This thesis will serve as a basis for future epidemiological applications looking into the nutrition-cancer relation

This study developed and validated the Youth Empowerment Scale (YES) for young people with psychosis. This PhD thesis consisted of four phases. Phase 1 conceptualised empowerment from the perspective of young people with psychosis. Phase 1 qualitative findings informed the development of the measurement of empowerment; the Youth empowerment Scale (YES). Phase 2 developed and validated the YES in a non-clinical population. Phase 3 explored the relationship between psychological processes (self-efficacy, control, coping, thinking style, and social support), empowerment, mental health wellbeing and recovery. The YES was then validated again in phase 4 on a clinical population, young people within Child and Adolescents Mental Health Services (CAMHS). This study confirmed that the YES is a valid and reliable measure of empowerment which can be used in future work identifying and supporting empowerment for young people with psychosis.