Tropical forests store more than half of the world’s forest carbon and are particularly threatened by deforestation and degradation processes, which together represent the second largest source of anthropogenic CO2 emissions. Consequently, tropical forests are the focus of international climate policies (i.e. Reducing emissions from deforestation and forest degradation, REDD) aiming at reducing forest-related CO2 emissions. The REDD initiative lies on our ability to map forest carbon stocks (i.e. spatial dynamics) and to detect deforestation and degradations (i.e. temporal dynamics) at large spatial scales (e.g. national, forested basin), with accuracy and precision. Remote-sensing is as a key tool for this purpose, but numerous sources of error along the carbon mapping chain makes meeting REDD criteria an outstanding challenge. In the present thesis, we assessed carbon (quantified through aboveground biomass, AGB) estimation error at the tree- and plot-level using a widely used pantropical AGB model, and at the landscape-level using a remote sensing method based on canopy texture features from very high resolution (VHR) optical data. Our objective was to better understand and reduce AGB estimation error at each level using information on large canopy tree structure, distribution and spatial organization. Although large trees disproportionally contributed to forest carbon stock, they are under-represented in destructive datasets and subject to an under-estimation bias with the pantropical AGB model. We destructively sampled 77 very large tropical trees and assembled a large (pantropical) dataset to study how variation in tree form (through crown sizes and crown mass ratio) contributed to this error pattern. We showed that the source of bias in the pantropical model was a systematic increase in the proportion of tree mass allocated to the crown in canopy trees. An alternative AGB model accounting for this phenomenon was proposed. We also propagated the AGB model bias at the plot-level and showed that the interaction between forest structure and model bias, although often overlooked, might in fact be substantial. We further analyzed the structural properties of crown branching networks in light of the assumptions and predictions of the Metabolic Theory of Ecology, which supports the power-form of the pantropical AGB model. Important deviations were observed, notably from Leonardo’s rule (i.e. the principle of area conservation), which, all else being equal, could support the higher proportion of mass in large tree crowns. A second part of the thesis dealt with the extrapolation of field-plot AGB via canopy texture features of VHR optical data. A major barrier for the development of a broad-scale forest carbon monitoring method based on canopy texture is that relationships between canopy texture and stand structure parameters (including AGB) vary among forest types and regions of the world. We investigated this discrepancy using a simulation approach: virtual canopy scenes were generated for 279 1-ha plots distributed on contrasted forest types across the tropics. We showed that complementing FOTO texture with additional descriptors of forest structure, notably on canopy openness (from a lacunarity analysis) and tree slenderness (from a bioclimatic proxy) allows developing a stable inversion frame for forest AGB at large scale. Although the approach we proposed requires further empirical validation, a first case study on a forests mosaic in the Congo basin gave promising results. Overall, this work increased our understanding of mechanisms behind AGB estimation errors at the tree-, plot- and landscape-level. It stresses the need to better account for variation patterns in tree structure (e.g. ontogenetic pattern of carbon allocation) and forest structural organization (across forest types, under different environmental conditions) to improve general AGB models, and in fine our ability to accurately map forest AGB at large scale.

Swimming performance strongly influences fitness in aquatic organisms and is closely tied to external body morphology. Although this connection has been closely examined at the individual and species level, few studies have focused on this relationship as it pertains to functional group assemblages. Using functional groups based on similarities in habitat use and morphology, I tested the hypothesis that swimming performance can be reliably predicted by functional group composition. I measured swimming performance as burst speed using a simulated predator attack and as prolonged speed using a step-endurance test in a laboratory flume. I measured morphology using geometric morphometric techniques. A difference in swimming behavior in four of the seven species was observed in the step-endurance test. Benthic species exhibited bracing behavior as an alternative to body-caudal fin (BCF) propulsion in the prolonged speed trials. Swimming performance exhibited a weak relationship with functional groups based on habitat or morphology. Rather a species-based model was the best predictor of swimming performance. Although species exhibited variation in swimming performance, body size was the strongest predictor of absolute swimming performance across all models. Relative swimming performance (measured in body lengths/sec) was negatively related to body size. The results of this study suggest that functional groups are not always reliable predictors of performance and they necessitate empirical testing to validate their effectiveness. This study also provides critical swimming performance data for previously unstudied Great Basin fishes which could be valuable for predicting fish passage through culverts, weirs and fish ladders.

Un nouveau règlement (CE) n° 1901/2006 établi par le Parlement européen et le Conseil de l’UE, relatif aux médicaments à usage pédiatrique, vise à améliorer la santé et la qualité de vie des enfants en Europe, en garantissant que les nouveaux médicaments pédiatriques et les médicaments déjà commercialisés seront pleinement adaptés à leurs besoins spécifiques. Ce règlement prévoit de nouvelles obligations pour l'industrie pharmaceutique, assorties de récompenses et d'incitations. Dans ce contexte, un plan d’investigation pédiatrique a été proposé pour l’ivabradine dans plusieurs sous-groupes de la population pédiatrique dans le traitement de l’insuffisance cardiaque chronique. L’ivabradine est une molécule déjà commercialisée chez l’adulte dans la prise en charge de l’angor, et de l’insuffisance cardiaque. Un premier travail a été d’aider au design de cette étude pédiatrique : évaluer la formulation pédiatrique, aider au choix de la dose initiale à administrer chez l’enfant, choisir le protocole de prélèvements et conseiller la méthode de prélèvements. Pour évaluer la formulation pédiatrique, une étude a été conduite pour déterminer la biodisponibilité relative de la formulation pédiatrique par rapport aux comprimés utilisés chez l’adulte. Une biodisponibilité relative similaire a été retrouvée entre les deux formulations. Une approche physiologique (PBPK « Physiollogically based PharmacoKineticsmodel ») a été utilisé pour prédire la dose initiale à administrer et pour proposer un protocole de prélèvements PK. La méthode DBS (Dried blood spot) consistant à collecter à chaque temps de prélèvement une goutte de sang (au pli du coude ou au bout du doigt) a été recommandée. La première dose à administrer chez l’enfant peut être également être déterminée par des modèles de population développés chez l’adulte et adaptés à l’enfant grâce à l’allométrie et à l’ajout de fonctions de maturation. Cette approche a été comparée au PBPK dans le cas de l’ivabradine et des résultats similaires ont été obtenus. Un deuxième travail a été réalisé après que l’étude clinique ait été conduite dans la population pédiatrique. L’étude a été menée chez 116 enfants (74 enfants recevant l’ivabradine, 42 recevant le placebo) âgés de 6 mois à 18 ans et les données ont été analysées. Tout d’abord, une relation a été établie entre les concentrations d’ivabradine plasmatiques et les concentrations d’ivabradine mesurées dans le sang total. Puis, afin de décrire les concentrations d’ivabradine et de son métabolite, un modèle de population prenant en compte l’effet de l’âge et du poids a été développé. En comparant les expositions plasmatiques, une dose par kilogramme plus élevée aurait été nécessaire chez les patients les plus jeunes pour atteindre un niveau d’exposition similaire aux patients plus âgés. Enfin, il a été monté que la relation PK/PD qui avait développé chez l’adulte était conservée dans la population pédiatrique. / New legislation governing the development and authorization of medicines for use in children was introduced in the European Union (EU) in January 2007. This Regulation aims to facilitate the development and accessibility of medicinal products for use in the paediatric population, to ensure that medicinal products used to treat the paediatric population are subject to ethical research of high quality and are appropriately authorised for use in the paediatric population, and to improve the information available on the use of medicinal products in the various paediatric populations. Several rewards and incentives for the development of paediatric medicines for children are available in the European Union (EU). In compliance with the paediatric European regulation, a study will be conducted in paediatric patients with CHF with the objective to determine the efficacious and safe dose of ivabradine, a compound already marketed in adults, and to assess its efficacy and safety in children over 1 year old. A first work was to help design a paediatric study for ivabradine focusing on: the paediatric formulation evaluation, the doses to be administered, the sampling design and the sampling technique. A study was conducted in order to assess the relative bioavailability (Frel) of the paediatric formulation and a similar Frel was observed between the paediatric formulation and the adult marketed tablet. PBPK modelling was used to predict initial doses to be administered in the paediatric study and to select the most appropriate sample time collections. The dried blood spot (DBS) technique was recommended in the clinical trial in children. A secondary objective was to perform a comparison of the prediction of ivabradine pharmacokinetics (PK) in children using a physiologically-based pharmacokinetic (PBPK) approach and allometric scaling of a population pharmacokinetic (PPK) model. Simulations obtained by both the PBPK approach and allometric scaling of a PPK model were compared a posteriori to the paediatric study observations. Both PPK and PBPK approaches allowed an adequate prediction of the PK of ivabradine and its metabolite in children. The second work was done after the study conduction in the paediatric population. The study was performed in 116 children (74 received ivabradine, 42 received the placebo) aged from 6 months to less than 18 years old and data were analysed. The relationship between blood and plasma concentrations was described using linear mixed effect models. In order to describe ivabradine and its metabolite blood concentrations in children, a joint population PK model was developed taking into account weight & age effects on PK parameters. Plasma exposure comparison indicated that higher dose/kg were necessary to achieve a similar exposure between younger and older children. The PK/PD relationship in adult patients is conserved in children.

Most climate change predictions focus on the response of individual species to changing local conditions and ignore species interactions, largely due to the lack of a sound theoretical foundation for how interactions are expected to change with climate and how to incorporate them into climate change models. Much of the variability in species interaction strengths may be governed by fundamental constraints on physiological rates, possibly providing a framework for including species interactions into climate change models. Metabolic rates, ingestion rates and many other physiological rates are relatively predictable from body size and body temperature due to constraints imposed by the physical and chemical laws that govern fluid dynamics and the kinetics of biochemical reaction times. My dissertation assesses the usefulness of this framework by exploring the community-level consequences of physiological constraints. In Chapter 2, I incorporated temperature and body size scaling into the biological rate parameters of a series of realistically structured trophic network models. The relative magnitude of the temperature scaling parameters affecting consumer energetic costs (metabolic rates) and energetic gains (ingestion rates) determined how consumer energetic efficiency changed with temperature. I systematically changed consumer energetic efficiency and examined the sensitivity of network stability and species persistence to various temperatures. I found that a species' probability of extinction depended primarily on the effects of organismal physiology (body size and energetic efficiency with respect to temperature) and secondarily on the effects of local food web structure (trophic level and consumer generality). This suggests that physiology is highly influential on the structure and dynamics of ecological communities. If consumer energetic efficiency declined as temperature increased, that is, species did best at lower temperatures, then the simulated networks had greater stability at lower temperatures. The opposite scenario resulted in greater stability at higher temperatures. Thus, much of the community-level response depends on what species energetic efficiencies at the organismal-level really are, which formed the research question for Chapter 3: How does consumer energetic efficiency change with temperature? Existing evidence is scarce but suggestive of decreasing consumer energetic efficiency with increasing temperature. I tested this hypothesis on seven rocky intertidal invertebrate species by measuring the relative temperature scaling of their metabolic and ingestion rates as well as consumer interaction strength under lab conditions. Energetic efficiencies of these rocky intertidal invertebrates declined and species interaction strengths tended to increase with temperature. Thus, in the rocky intertidal, the mechanistic effect of temperature would be to lower community stability at higher temperatures. Chapter 4 tests if the mechanistic effects of temperature on ingestion rates and species interaction strengths seen in the lab are apparent under field conditions. Bruce Menge and I related bio-mimetic estimates of body temperatures to estimates of per capita mussel ingestion rates and species interaction strengths by the ochre sea star Pisaster ochraceus, a keystone predator of the rocky intertidal. We found a strong, positive effect of body temperature on both per capita ingestion rates and interaction strengths. However, the effects of season and the unique way in which P. ochraceus regulates body temperatures were also apparent, leaving room for adaptation and acclimation to partially compensate for the mechanistic constraint of body temperature. Community structure of the rocky intertidal is associated with environmental forcing due to upwelling, which delivers cold, nutrient rich water to the nearshore environment. As upwelling is driven by large-scale atmospheric pressure gradients, climate change has the potential to affect a wide range of significant ecological processes through changes in water temperature. In Chapter 5, my coauthors and I identified long-term trends in the phenology of upwelling events that are consistent with climate change predictions: upwelling events are becoming stronger and longer. As expected, longer upwelling events were related to lower average water temperatures in the rocky intertidal. Furthermore, recruitment rates of barnacles and mussels were associated with the phenology of upwelling events. Thus climate change is altering the mode and the tempo of environmental forcing in nearshore ecosystems, with ramifications for community structure and function. Ongoing, long-term changes in environmental forcing in rocky intertidal ecosystems provide an opportunity to understand how temperature shapes community structure and the ramifications of climate change. My dissertation research demonstrates that the effect of temperature on organismal performance is an important force structuring ecological communities and has potential as a tractable framework for predicting the community level effects of climate change. / Graduation date: 2013 / Access restricted to the OSU Community, at author's request, from Nov. 20, 2012 - Nov. 20, 2014

Com a entrada em vigor do Protocolo de Quioto, intensificam-se as expectativas pela regulamentação de um mercado de créditos de carbono. No caso de esses créditos terem sua origem em projetos de reflorestamento ou de florestamento, conforme previsto pelos chamados Mecanismos de Desenvolvimento Limpo (MDL), vem a ser fundamental o estabelecimento de uma metodologia para quantificação de estoques de carbono armazenados sob a forma de biomassa vegetal. Este trabalho propõe, como um método informatizado para cálculo de estoque de carbono em florestas, um conjunto de funcionalidades e um modelo de dados cadastrais totalmente integrados com um Sistema de Informações Geográficas de arquitetura aberta. A partir de mapas e imagens geo-referenciadas e com base em dados obtidos de pequenos transectos, o sistema calcula a quantidade total de carbono estocada em toda a floresta. Além de permitir apresentar esses resultados para diferentes agentes armazenadores de carbono, como, por exemplo, segmentos de floresta ou cada espécie vegetal, o sistema mantém registro histórico de dados dendrométricos, o que virá permitir a geração de gráficos de curvas de crescimento e, por conseguinte, estimativas futuras. / Increasing expectation for the carbon credit market regulamentation take place as a result of the Kyotos Protocol enforcement. In case of credits that come from reforestation or forestation projects, as foresseen under the Clean Development Mechanism (CDM), it is fundamental to establish a methodology for quantification of carbon stocks stored under the vegetal biomass form. This work proposes, as an informatizated method of forests carbon stocks calculation, a set of functionalities and a cadastre data model totally integrated with an open architeture of Geographyc Information System. Based on maps and images georeferenced on data basis provided by small transectos, the system calculates the total amount of carbon storages all over the forest. Besides allowing to present the results to different storing carbon agents, for instance, forests segments or each vegetal species, the system keeps historical register of dendrometrics data, which will make possible the generation of graphs, curves of growth and, therefore, future evaluation.

Com a entrada em vigor do Protocolo de Quioto, intensificam-se as expectativas pela regulamentação de um mercado de créditos de carbono. No caso de esses créditos terem sua origem em projetos de reflorestamento ou de florestamento, conforme previsto pelos chamados Mecanismos de Desenvolvimento Limpo (MDL), vem a ser fundamental o estabelecimento de uma metodologia para quantificação de estoques de carbono armazenados sob a forma de biomassa vegetal. Este trabalho propõe, como um método informatizado para cálculo de estoque de carbono em florestas, um conjunto de funcionalidades e um modelo de dados cadastrais totalmente integrados com um Sistema de Informações Geográficas de arquitetura aberta. A partir de mapas e imagens geo-referenciadas e com base em dados obtidos de pequenos transectos, o sistema calcula a quantidade total de carbono estocada em toda a floresta. Além de permitir apresentar esses resultados para diferentes agentes armazenadores de carbono, como, por exemplo, segmentos de floresta ou cada espécie vegetal, o sistema mantém registro histórico de dados dendrométricos, o que virá permitir a geração de gráficos de curvas de crescimento e, por conseguinte, estimativas futuras. / Increasing expectation for the carbon credit market regulamentation take place as a result of the Kyotos Protocol enforcement. In case of credits that come from reforestation or forestation projects, as foresseen under the Clean Development Mechanism (CDM), it is fundamental to establish a methodology for quantification of carbon stocks stored under the vegetal biomass form. This work proposes, as an informatizated method of forests carbon stocks calculation, a set of functionalities and a cadastre data model totally integrated with an open architeture of Geographyc Information System. Based on maps and images georeferenced on data basis provided by small transectos, the system calculates the total amount of carbon storages all over the forest. Besides allowing to present the results to different storing carbon agents, for instance, forests segments or each vegetal species, the system keeps historical register of dendrometrics data, which will make possible the generation of graphs, curves of growth and, therefore, future evaluation.

Introduction: No Fixed-Dose Combination (FDC) formulations currently exist for pediatric tuberculosis (TB) treatment. Earlier work implemented, in the software NONMEM, a rational method for optimizing design and individualization of pediatric anti-TB FDC formulations based on patient body weight, but issues with parameter estimation, dosage strata heterogeneity and representative pharmacokinetics remained. Aim: To further develop the rational model-based methodology aiding the selection of appropriate FDC formulation designs and dosage regimens, in pediatric TB treatment. Materials and Methods: Optimization of the method with respect to the estimation of body weight breakpoints was sought. Heterogeneity of dosage groups with respect to treatment efficiency was sought to be improved. Recently published pediatric pharmacokinetic parameters were implemented and the model translated to MATLAB, where also the performance was evaluated by stochastic estimation and graphical visualization. Results: A logistic function was found better suited as an approximation of breakpoints. None of the estimation methods implemented in NONMEM were more suitable than the originally used FO method. Homogenization of dosage group treatment efficiency could not be solved. MATLAB translation was successful but required stochastic estimations and highlighted high densities of local minima. Representative pharmacokinetics were successfully implemented. Conclusions: NONMEM was found suboptimal for the task due to problems with discontinuities and heterogeneity, but a stepwise method with representative pharmacokinetics were successfully implemented. MATLAB showed more promise in the search for a method also addressing the heterogeneity issue.

Les perturbations auxquelles font face les communautés écologiques, du fait des activités humaines, sont à l'origine de changements profonds dans ces communautés. Nombreuses caractéristiques des espèces sont altérées, de leur physiologie à leur occurrence même. Ces changements se répercutent sur la composition, la diversité et la structure des communautés, puisque les espèces n'interagissent pas tout le temps de la même manière en fonction des conditions. Prévoir le devenir de ces communautés émergentes, et des fonctions qu'elles soutiennent est un défi central de l'écologie et de nos sociétés. Différents cadres conceptuels ont été utilisés pour relever ce défi, basés sur différents mécanismes écologiques, et ont divergé en plusieurs domaines. D'un côté, l'analyse des chaînes trophiques utilise la consommation pour expliquer les effets de la diversité verticale (le nombre de niveaux trophiques) sur le fonctionnement, et de l'autre côté, les analyses biodiversité-fonctionnement lient compétition et effets de la diversité horizontale (la diversité au sein des niveaux trophiques isolés). Chacun de ces domaines a produit des résultats clés pour comprendre les conséquences fonctionnelles des changements de composition et diversité des communautés écologiques. Cependant, ils sont chacun basés sur différentes simplifications fortes des communautés. L'hypothèse qui sous-tend cette thèse est que la réconciliation en un même cadre de travail des résultats fondamentaux de ces champs conceptuels divergents, ainsi que des effets des changements de structure de la biodiversité, est une étape clé pour pouvoir améliorer notre compréhension du fonctionnement de communautés écologiques en changement. L'essor récent des méthodes d'analyse des réseaux trophiques, et des modèles permettant de simuler le fonctionnement de ces réseaux trophiques offre un cadre idéal pour cette réconciliation. En effet, les réseaux trophiques cartographient les échanges de matière entre toutes les espèces d'une communauté, permettant la mise en place d'interactions variées. Ils reflètent mieux la réalité complexe des communautés que les chaînes trophiques ou leurs niveaux trophiques isolés en intégrant notamment compétition et consommation. Un modèle ressource-consommateur bioénergétique classique, développé par Yodzis et Innes (1992), permet d'en simuler le fonctionnement, en intégrant des mécanismes et taux testés empiriquement. Au-delà d'utiliser ces outils, cette thèse se concentre aussi sur leur évaluation. Après un premier chapitre d'introduction, le second chapitre propose une plateforme ouverte, commune, solidement testée et efficace pour l'utilisation du modèle bioénergétique, permettant ainsi une synthèse plus rapide et aisée des résultats. Le troisième chapitre est une revue du corpus méthodologique d'analyse des réseaux trophiques, proposant une gamme de méthodes robustes et informatives, et soulignant leur domaine d'application et leurs limites. Enfin le quatrième chapitre met ce cadre méthodologique à l'épreuve. Dans ce chapitre, nous montrons l'existence d'une relation entre la complexité de la structure du réseau trophique des communautés et leur régime de fonctionnement, se traduisant par la réalisation de différentes prédictions issues de l'analyse des chaînes trophiques ou des analyses diversité-fonctionnement. Cette mise en évidence des conditions structurelles pour la réalisation de différentes prédictions nous permet de mieux comprendre quels mécanismes écologiques prédominent selon différentes conditions, dirigeant l'effet de la diversité sur le fonctionnement. / Human-driven disturbances are causing profound changes in ecological communities, as many characteristics of species are altered, from their physiology to their very occurrence. These changes affect the composition, diversity and structure of communities, since species do not always interact in the same way under different conditions. Predicting the fate of these emerging communities, and the functions they support, is a central challenge for ecology and our societies. Diverging conceptual frameworks have been used to address this challenge, based on different ecological mechanisms. On the one hand, food chain analysis uses consumption to explain the effects of vertical diversity (the number of trophic levels) on functioning, and on the other hand, biodiversity-functioning analyses link competition and the effects of horizontal diversity (diversity within isolated trophic levels). Each of these domains has produced key results for understanding the functional consequences of changes in the composition and diversity of ecological communities. However, they are each based on different strong simplifications of communities. The hypothesis underlying this thesis is that reconciling the fundamental results of these divergent conceptual fields, as well as the effects of changes in the structure of biodiversity, into a single framework is a key step towards improving our understanding of the functioning of changing ecological communities. The recent development of food web analysis and of models to simulate food webs functioning provides an ideal framework for this reconciliation. Food webs map the exchange of matter between all species in a community, allowing for a variety of interactions to take place. They better reflect the complex reality of communities than food chains or their isolated trophic levels, notably by integrating competition and consumption. A classical consumer-resource bioenergetic model developed by Yodzis and Innes (1992) specifically makes it possible to realistically simulate their functioning, using empirically tested mechanisms and rates. Beyond using these tools, this thesis focuses on their evaluation and implementation. After a first, introductory chapter, the second chapter proposes an open, common, well-tested and efficient platform for the use of the bioenergetic model, allowing a faster and easier synthesis of the results. The third chapter is a review of the methodological corpus for ecological networks analysis, outlining a range of robust and informative methods, and highlighting their scope and limitations. Finally, the fourth chapter puts this methodological framework to the test. In this chapter, we show the existence of a relationship between the complexity of communities' food-web structure and functioning regime, resulting in the realization of different predictions from food chain analysis or diversity-functioning analyses. This demonstration of the structural conditions for the realization of different predictions allows us to better understand which ecological mechanisms predominate under different conditions, directing the effect of diversity on functioning.