Humans experience ubiquitous exposures to estrogenic environmental chemicals from food, personal care products, and other industrial and consumer goods. Bisphenol A (BPA), a well-studied xenoestrogen, is known to alter development of estrogen-sensitive organs including the brain, reproductive tract, and mammary gland. Bisphenol S (BPS), which has a similar chemical structure to BPA, is also used in many consumer products, but its effects on estrogen-sensitive organs in mammals has not been thoroughly examined. In our study, pregnant CD-1 mice were orally exposed to BPS or ethinyl estradiol (EE2, a positive control for estrogenicity) from gestational day 9 through postnatal day (PND) 2, the period when many estrogen-sensitive organs are developing. After weaning, the offspring were administered either oil (vehicle) or an estrogen challenge (1 μg EE2/kg/day) for ten days starting at PND21 (prior to puberty), PND80 (early adulthood), or PND260 (later adulthood). Timing of puberty was evaluated in females by noting the date on which vaginal opening occurred. After the 10 day estrogen challenge, we evaluated the response of endocrine sensitive organs through measurements of organ weight, tissue morphology, and gene expression in both males and females. We observed dose- and sex-specific effects of BPS and EE2 treatment, as well as alterations in the responses of males and females to the estrogen challenge. This study sheds light on the effects of low dose xenoestrogen exposures on estrogen-sensitive organs including the reproductive tract and mammary gland. Furthermore, it improves our understanding of the influence of environmental chemicals on secular trends of earlier age of puberty in girls reported over the past few decades.

Ce projet combine l’archéologie expérimentale, l’analyse morphométrique et la comparaison des résultats à l’assemblage archéologique de l’Abri Cellier (Dordogne, France) (N = 12) dans le but de quantifier l’apport du réaffûtage à la variabilité des formes et des dimensions des pointes de projectile aurignaciennes en bois de cervidé. La relecture morphofonctionnelle de la série expérimentale de Knecht (N = 79) couplée à une reproduction expérimentale récente (N = 9) démontre que la nature des dommages infligés au fût des pointes dépend (1) de la force du tir, (2) de la nature de la cible impactée et, (3) des propriétés biomécaniques du matériau employé. Pour sa part, le réaffûtage dépend (1) de l’expérience du réaffûteur et, (2) de la séquence technique employée. Ce comportement est standardisé et demeure indépendant du type de pointe de même que du type de dommage du fût. Les changements morphométriques associés à ce comportement se résument (1) à un déplacement progressif de l’épaule de la base vers le fût de la pointe, (2) à une tendance à l’accroissement de l’angle du fût et, (3) à une localisation des traces de réaffûtage sur le tiers distal de la partie distale de la pointe. Puisque l’utilisation et le réaffûtage sont deux processus impossible à départager sur les artefacts, nous proposons l’adoption d’une mesure, le ratio proximo-distal (RP/D) afin de traduire l’intensité de ces processus convergents et faciliter la comparaison entre les assemblages archéologiques. / This project combines experimental archaeology and morphometric analysis with a comparison with the archaeological assemblage from Abri Cellier (Dordogne, France) (N = 12) to quantify the contribution of resharpening to morphometric variability of Aurignacian projectile points made of antler. A morpho-functional re-analysis was performed on the experimental series produced by Knecht (N = 79), and combined with a recent experiment (N = 9) which showed that tip damage depends on (1) the projectile velocity, (2) the nature of the impacted target and, (3) the raw material’s biomechanical properties. On the other hand, resharpening depends on (1) the curator’s experience and, (2) the employed technical sequence. Also, resharpening is considered a standardized behaviour that remains independent of the point or tip damage type. Morphometric changes incurred by this behaviour can be summarized by (1) a gradual shift of the point’s shoulder from the base to the tip of the point, (2) a tendency of the tip to become more obtuse, and (3) a concentration of the curation stigmata at the distal third of the tip. Since use and resharpening are two processes that can’t be distinguished metrically on archaeological specimens, we propose a new metric the Proximo-Distal Ratio (RP/D), which translates the intensity of these two converging processes and allows inter-assemblage comparison.

Introdução: A histomorfometria do osso é um dos métodos padronizados que pode ser utilizado para quantificar a microestrutura do osso trabecular. Existem muitos meios de acesso para conseguir a visualização dos defeitos ósseos no caso de um acometimento de doença periodontal, por exemplo. A extensão e morfologia da perda óssea alveolar podem ser acessadas e examinadas após confecção de retalhos mucoperiosteais em cirurgias periodontais ou através de exames radiográficos. A partir de então, a tecnologia da micro- CT tornou-se padrão ouro para avaliação da arquitetura 3D do osso trabecular; exibindo como uma de suas principais vantagens sua habilidade em proporcionar resultados quantitativos com pouco ou nenhum preparo da amostra e sem a sua destruição. Metodologia: Foram utilizados 40 ratos machos: ratos normotensos (WK) e espontaneamente hipertensos (SHR) foram divididos em grupos com doença periodontal induzida por ligaduras (DP), e grupos controle, em que a DP não foi induzida (C). Cada um desses quatro grupos foram divididos em 2 subgrupos, de acordo com o período de eutanásia, que foi realizada no 10° e no 21° dia do experimento, desse modo cada grupo teve um n=5. Os animais do grupo DP receberam ligadura com fio de algodão ao redor do primeiro molar inferior. Após a eutanásia todas as hemimandíbulas dos animais tiveram seu tecido mole removido através de processos químico e biológico a fim de proporcionar uma peça histológica preparada adequadamente para ser escaneada no microtomógrafo. Para realização da análise microtomográfica foi utilizado um aparelho modelo 1172 da fabricante SkyScan®. As amostras foram verificadas nos três planos espaciais através dos softwares CTAN®, DATA VIEWER® e CTVOX® que também foram utilizados para a visualização tridimensional, análise qualitativa e quantitativa da anatomia externa e interna do osso alveolar. Resultados: Os resultados das medidas lineares foram aqueles extraídos de uma imagem bidimensional de uma fatia única escolhida por ser a mais representativa para detectar a perda óssea alveolar. Para a quantificação dos parâmetros volumétricos foi realizada a avaliação em dois pontos distintos: a área da região de furca do M1 mandibular e a área da região interproximal entre M1 e M2 da mandíbula. De todos os parâmetros avaliados e analisados os mais representativos para detectar a perda óssea alveolar neste modelo de estudo foram: Furca e JCE-COV (junção cemento-esmalte crista óssea vestibular) em 2D (medidas lineares) e a relação entre a superfície óssea e o volume ósseo; relação entre o volume ósseo e o volume total; porosidade e densidade mineral óssea nos parâmetros em 3D (medidas volumétricas). Conclusão: A metodologia empregada mostrou ser eficiente para a caracterização da perda óssea alveolar nos grupos controle e doença periodontal. A região escolhida e o método de análise tem influência no resultado. Assim medidas lineares e medidas volumétricas de uma mesma amostra podem apresentar porcentagens diferentes em relação à perda óssea. / Introduction: The histomorphometry of bone is one of the standard methods that can be used to quantify the microstructure of the trabecular bone. There are many ways to get access to the visualization of bone defects in the case of onset of periodontal disease, for example. The extent and morphology of alveolar bone loss may be accessed and examined after making mucoperiosteais flaps in periodontal or through radiographic examinations surgeries. Since then, the technology of micro - CT has become the gold standard for evaluation of the 3D architecture of trabecular bone; showing as one of its main advantages its ability to provide quantitative results without destruction and with little or no sample preparation. Methodos: Normotensive rats (WK) and spontaneously hypertensive (SHR) were divided into groups of ligature-induced periodontal disease (PD), and control groups (C), where PD is not induced. 40 rats were used and each of these four groups were divided into 2 subgroups according to the time of euthanasia , which was held on the 10th and 21st day of the experiment , thus each group had an n = 5 . The animals in the PD group received ligature with cotton thread around the first molar. After euthanasia, all animals had their mandibles soft tissue removed through chemical and biological processes to provide a suitably prepared for micro-ct analysis. In order to perform the micro-CT analysis, a model 1172 device manufacturer of SkyScan® was used. The samples were observed in the three spatial planes through the CTAN®, DATA VIEWER® and CTVOX® softwares which were also used for threedimensional visualization, qualitative and quantitative analysis of the external and internal anatomy of the alveolar bone. Results: The results of linear measurements were those extracted from a twodimensional image of a single slice chosen for being the most representative for detecting bone loss. For quantification of the volumetric parameters were assessed at two different points: the area of the furcation region of the mandibular M1 and interproximal area of the region between M1 and M2 of the jaw. Of all the most representative in detecting alveolar bone loss in this model of study parameters were evaluated and analyzed : Furcation and cementum-enamel junction to the buccal bone crest = 2D (linear measurements) and the relationship between the bone surface and bone volume ; ratio of bone volume to the total volume ; porosity and bone mineral density in 3D parameters ( volumetric measurements). Conclusion: The methodology was efficient for the characterization of alveolar bone loss in the periodontal disease groups. The region chosen and method of analysis have affected the outcome. Thus, linear and volumetric measurements of the same sample may have different percentages in relation to bone loss.

Introdução: A histomorfometria do osso é um dos métodos padronizados que pode ser utilizado para quantificar a microestrutura do osso trabecular. Existem muitos meios de acesso para conseguir a visualização dos defeitos ósseos no caso de um acometimento de doença periodontal, por exemplo. A extensão e morfologia da perda óssea alveolar podem ser acessadas e examinadas após confecção de retalhos mucoperiosteais em cirurgias periodontais ou através de exames radiográficos. A partir de então, a tecnologia da micro- CT tornou-se padrão ouro para avaliação da arquitetura 3D do osso trabecular; exibindo como uma de suas principais vantagens sua habilidade em proporcionar resultados quantitativos com pouco ou nenhum preparo da amostra e sem a sua destruição. Metodologia: Foram utilizados 40 ratos machos: ratos normotensos (WK) e espontaneamente hipertensos (SHR) foram divididos em grupos com doença periodontal induzida por ligaduras (DP), e grupos controle, em que a DP não foi induzida (C). Cada um desses quatro grupos foram divididos em 2 subgrupos, de acordo com o período de eutanásia, que foi realizada no 10° e no 21° dia do experimento, desse modo cada grupo teve um n=5. Os animais do grupo DP receberam ligadura com fio de algodão ao redor do primeiro molar inferior. Após a eutanásia todas as hemimandíbulas dos animais tiveram seu tecido mole removido através de processos químico e biológico a fim de proporcionar uma peça histológica preparada adequadamente para ser escaneada no microtomógrafo. Para realização da análise microtomográfica foi utilizado um aparelho modelo 1172 da fabricante SkyScan®. As amostras foram verificadas nos três planos espaciais através dos softwares CTAN®, DATA VIEWER® e CTVOX® que também foram utilizados para a visualização tridimensional, análise qualitativa e quantitativa da anatomia externa e interna do osso alveolar. Resultados: Os resultados das medidas lineares foram aqueles extraídos de uma imagem bidimensional de uma fatia única escolhida por ser a mais representativa para detectar a perda óssea alveolar. Para a quantificação dos parâmetros volumétricos foi realizada a avaliação em dois pontos distintos: a área da região de furca do M1 mandibular e a área da região interproximal entre M1 e M2 da mandíbula. De todos os parâmetros avaliados e analisados os mais representativos para detectar a perda óssea alveolar neste modelo de estudo foram: Furca e JCE-COV (junção cemento-esmalte crista óssea vestibular) em 2D (medidas lineares) e a relação entre a superfície óssea e o volume ósseo; relação entre o volume ósseo e o volume total; porosidade e densidade mineral óssea nos parâmetros em 3D (medidas volumétricas). Conclusão: A metodologia empregada mostrou ser eficiente para a caracterização da perda óssea alveolar nos grupos controle e doença periodontal. A região escolhida e o método de análise tem influência no resultado. Assim medidas lineares e medidas volumétricas de uma mesma amostra podem apresentar porcentagens diferentes em relação à perda óssea. / Introduction: The histomorphometry of bone is one of the standard methods that can be used to quantify the microstructure of the trabecular bone. There are many ways to get access to the visualization of bone defects in the case of onset of periodontal disease, for example. The extent and morphology of alveolar bone loss may be accessed and examined after making mucoperiosteais flaps in periodontal or through radiographic examinations surgeries. Since then, the technology of micro - CT has become the gold standard for evaluation of the 3D architecture of trabecular bone; showing as one of its main advantages its ability to provide quantitative results without destruction and with little or no sample preparation. Methodos: Normotensive rats (WK) and spontaneously hypertensive (SHR) were divided into groups of ligature-induced periodontal disease (PD), and control groups (C), where PD is not induced. 40 rats were used and each of these four groups were divided into 2 subgroups according to the time of euthanasia , which was held on the 10th and 21st day of the experiment , thus each group had an n = 5 . The animals in the PD group received ligature with cotton thread around the first molar. After euthanasia, all animals had their mandibles soft tissue removed through chemical and biological processes to provide a suitably prepared for micro-ct analysis. In order to perform the micro-CT analysis, a model 1172 device manufacturer of SkyScan® was used. The samples were observed in the three spatial planes through the CTAN®, DATA VIEWER® and CTVOX® softwares which were also used for threedimensional visualization, qualitative and quantitative analysis of the external and internal anatomy of the alveolar bone. Results: The results of linear measurements were those extracted from a twodimensional image of a single slice chosen for being the most representative for detecting bone loss. For quantification of the volumetric parameters were assessed at two different points: the area of the furcation region of the mandibular M1 and interproximal area of the region between M1 and M2 of the jaw. Of all the most representative in detecting alveolar bone loss in this model of study parameters were evaluated and analyzed : Furcation and cementum-enamel junction to the buccal bone crest = 2D (linear measurements) and the relationship between the bone surface and bone volume ; ratio of bone volume to the total volume ; porosity and bone mineral density in 3D parameters ( volumetric measurements). Conclusion: The methodology was efficient for the characterization of alveolar bone loss in the periodontal disease groups. The region chosen and method of analysis have affected the outcome. Thus, linear and volumetric measurements of the same sample may have different percentages in relation to bone loss.

Les avalanches de débris, qui résultent du démantèlement des flancs des édifices volcaniques et montagneux, sont des écoulements granulaires rapides et dangereux dont le monteur est la gravité et qui présentent des distances de transport extrêmement importantes. La dynamique de leur mise en place et leurs mécanismes de transport permettant cette très grande mobilité sont des phénomènes qui demeurent encore mal compris. De nombreux modèles existent pour expliquer la grande mobilité des avalanches de débris et incluent des processus basés sur la lubrification ou la fluidification de la masse granulaire mais également sur le phénomène de désintégration dynamique des éléments. Cependant la grande majorité des modèles proposés souffre du manque d’observations de terrain et de quantification de l’évolution des matériaux au cours de leur transport au sein de la masse granulaire. Afin d’identifier les principaux mécanismes de transport des avalanches de débris, nous proposons dans ce travail une étude de terrain détaillée de dépôts d’avalanches de débris volcaniques qui résultent du démantèlement d’un volcan bouclier océanique, le Piton des Neiges (île de La Réunion, océan Indien). L’approche est couplée à un examen morphométrique (dimension fractale et circularité), exoscopique et granulométrique des particules présentes dans les dépôts. Elle est complétée par l’examen de la fabrique des dépôts basée sur l’anisotropie de la susceptibilité magnétique (ASM). Les données obtenues nous permettent de mettre en évidence une évolution de la dynamique de transport et de mise en place des dépôts d’avalanches de débris depuis les zones sources jusqu’aux domaines de dépôt distaux. On montre également que la désintégration dynamique et le gonflement dispersif qui l’accompagne opèrent tout au long du transport et à toutes les échelles au-dessus d’une limite inférieure de broyage à 500 μm. En dessous de cette limite, la réduction granulométrique résulte uniquement de processus d’attrition par friction entre les particules. La grande mobilité des avalanches de débris pourrait ainsi être expliquée par l’effet combiné de la libération d’énergie élastique par la désintégration dynamique des particules > 500μm et par une réduction de la friction interne à la matrice liée aux interactions dispersives des particules fines (< 500 μm). L’ensemble des données permettent également de préciser les directions de transport et l’ampleur des avalanches de débris liées aux déstabilisations du massif du Piton des Neiges. / Debris avalanches, resulting from flank collapses that shape volcanic and mountainous edifices are rapidand dangerous gravity-driven granular flows that travel long run out distances. The dynamic and the transport mechanisms behind this high mobility remain poorly understood. The numerous models proposed to explain this high mobility include processes based on lubrication or fluidisation of the granular mass of the flow body, but also the dynamic disintegration of the transported particles. To date,all these proposed mechanisms lack observational support and quantification of the state of the particles of the granular mass during the transport. To identify the main transport mechanisms, we propose here detailed field studies of volcanic debris avalanches deposits resulting of flank-collapse events on an oceanic shield volcano, the Piton des Neiges (La Réunion Island, Indian Ocean). This study has been combined with morphometric (fractal dimension and circularity), exoscopic and grain-size analyses. Moreover, the fabric of the deposits has been investigated by with the characteristics of the anisotropy of the magnetic susceptibility (ASM). From these data we highlight a proximal to distal evolution of the debris avalanches transport and emplacement dynamics. We demonstrate that syn-transport dynamic disintegration continuously operates with the distance from the source down to a grinding limit of 500μm. Below this limit, the particle size reduction exclusively results from the attrition of the particles by frictional interactions. Thus, the exceptional mobility of debris avalanches may be explained by thecombined effect of elastic energy release during the dynamic disintegration of the larger clasts (> 500μm) and frictional reduction within the matrix due to the dispersive interactions between the finer particles (< 500 μm). All these data also allow to specify the transport direction and the approximate size of the debris avalanches related to the Piton des Neiges destabilisations.

La paralysie obstétricale du plexus brachial (POPB) est une paralysie du membre supérieur qui survient à la naissance et peut entraîner une déformation de l'articulation et un fonctionnement anormal de l'épaule. Bien que le traitement de la POPB tente de restaurer la fonction de l'épaule, la pathomécanique sous-jacente n'est pas encore clairement comprise. Les modèles computationnels sont efficaces pour fournir de telles informations, mais il n'existe aucun modèle d'articulation de l'épaule pédiatrique pour comprendre la POPB. Ainsi, ce travail de recherche a pour but de construire un framework combinant les avancées dans les domaines de la modélisation statistique de forme (MSF) et de la modélisation musculo-squelettique multi-corps (MCM). Due à l’insuffisance des données dans la cohorte pédiatrique, ce cadre a été mis en place pour l'articulation de l'épaule adulte. Pour cela, la précision de la MSF a été illustrée en prédisant 1) la forme de l'omoplate pré-morbide, et 2) les régions d'insertion musculaire sur l'omoplate et l'humérus. Cette méthode a ensuite été intégrée aux modèles MCM pour l'épaule adulte pour souligner l’importance des modèles spécifique-patient pour l’usage clinique. Pour le second objectif de cette thèse, j'ai développé un modèle MCM pédiatrique du complexe articulaire de l'épaule en utilisant le logiciel OpenSim. Grâce aux approches de cinématique et dynamique inverse, le modèle a permis de déterminer les différences de dynamique articulaires entre le côté sain et le côté pathologique. Les travaux futurs seront axés sur l’extension du travail réalisé pour la population pédiatrique afin de comprendre la pathomécanique de POPB. / Obstetrician Brachial Plexus Palsy (OBPP) is a common birth injury in children leading to shoulder joint deformity and abnormal function. While the management of OBPP disorder focuses on restoring the shoulder joint function, the underlying pathomechanics is not clearly understood yet. Computational models are effective to provide such insights, however, there is no pediatric shoulder joint model to understand the OBPP disorder. Thus, the global aim of this research work was to build a computational framework combining the advances in statistical shape modeling (SSM) and multi-body musculoskeletal modeling (MSKM) domains. Due to a lack of sufficient data in the pediatric cohort, I first developed the framework for adult shoulder joint. For this, I illustrated the accuracy of SSM in predicting 1) missing part of the scapula, and 2) muscle insertion regions on scapula and humerus bones. This method was then integrated with adult shoulder MSKMs to show the differences between generic and subject specific constructs. For the second aim of this thesis, I developed a pediatric MSKM of the shoulder joint complex using OpenSim software. Pediatric MSKM represented scapulothoracic, sternoclavicular, acromioclavicular, and glenohumeral joints with 13 degrees of freedom, and actuated by 52 musculotendon actuators representing 14 shoulder muscles. Using inverse kinematics and inverse dynamics approaches, the model was used to determine the differences in joint kinematics, and joint dynamics between healthy and unhealthy side of a single OBPP subject. Future work is focused on completing the framework on pediatric population and understanding the pathomechanics of OBPP.