Antibiotics have been one of the greatest scientific discoveries for humanity. Their great success has been hindered by the increasing of antibiotic resistance events. Conventional wisdom considers antibiotic resistance as a strictly clinical issue. In reality, more and more studies have proven that non-clinical environments, especially aquatic environments, are critical factors for the spread of antibiotic resistance. Antibiotic resistance genes (ARGs) are usually located on mobile genetic elements, which can disseminate among taxonomically unconnected species. Therefore, environmental bacteria can serve as hotspots for the development and dissemination of antibiotic resistance. The aim of this thesis is to determine how human originated pollution affects the antibiotic resistance abundance in the surrounding water environments. The case studies were three example environments, wastewater treatment plants (WWTPs), receiving river bodies and combined sewer overflows (CSOs). Molecular microbiology methods have been applied to analyse the resistance levels of bacterial communities from WWTP, CSOs and wastewater affected environments at different European geographical locations. Additionally, a novel approach consisting in an amplicon sequencing is described, in order to be able to investigate and asses the composition of a significant amount of integron gene cassettes. Findings consistently indicate that effluents originated from WWTPs and CSOs have a significant impact on the levels of ARGs of the receiving water bodies. Moreover, this thesis suggests that gene blaOXA-58, could be utilized as a proxy to investigate the spread of ARGs. Its occurrence has been reported to show, consistently throughout the chapters, lower concentrations upstream, but at higher concentrations in the WWTP effluent, CSOs and downstream of the effluent. In conclusion, although antibiotic resistance genes and integrons are part of the environmental resistome, water environments that are affected by anthropogenic wastewater display high levels of the above-mentioned genetic elements. These findings clearly suggest the need to limit pollution levels, as well as the need to establish a more responsible policy in antibiotic prescriptions. This must take place in order to be able to perform efficient risk assessments and to establish acceptable levels of antibiotic and ARGs pollution.:List of Figures VII List of Tables IX List of Abbreviations X 1. Introduction 11 1.1 Antibiotic resistance: an increasing problem 11 1.2 Intrinsic antibiotic resistance and horizontal gene transfer 13 1.2.1 Transformation 13 1.2.2 Transduction 13 1.2.3 Conjugation 14 1.3 Gene transfer elements 14 1.4 Antibiotic resistance and anthropogenic impact on surrounding environments 16 1.5 Study goals 17 2. Genetic variations of the resistome of wastewater treatment plants driven by the seasonality of antibiotic prescription 18 2.1 Introduction 18 2.2 Materials and methods 19 2.3 Results and discussion 20 3. Assessment of inter-laboratory variations of quantitative analyses of antibiotic resistance genes 27 3.1 Introduction 27 3.2 Materials and methods 27 3.3 Results and discussion 30 3.4 Conclusions 36 4. Antibiotic resistance genes in treated wastewater and in the receiving water bodies: A pan-European survey of urban settings 37 4.1 Introduction 37 4.2 Materials and methods 38 4.3 Results 44 4.4 Discussion 49 4.5 Conclusions 53 5. Analysis of integron gene cassettes composition in treated wastewater 55 5.1 Introduction 55 5.2 Materials and methods 55 VI 5.3 Results 56 5.4 Discussion 57 6. Role of combined sewer overflows in the dissemination of antibiotic resistance in surrounding environments 59 6.1 Introduction 59 6.2 Materials and methods 60 6.3 Results 61 6.4 Discussion 66 7. Closing Conclusions 68 References 70 List of publications 88 Note on the commencement of the doctoral procedure 89 Acknowledgments 90

Researchers use datasets of Question-Solution pairs to train machine learning models, such as source code generation models. A Question-Solution pair contains two parts: a programming question and its corresponding Solution Snippet. A Solution Snippet is a source code that solves a programming question. These datasets of Question-Solution pairs can be extracted from a number of different platforms. In this research, I study how Question-Solution pairs are extracted from Stack Overflow (SO). There are two limitations of datasets of Question-Solution pairs extracted from SO: (1) according to the authors of these datasets, some Question-Solution pairs contain Solution Snippets that do not solve the question correctly, and (2) these datasets do not contain the information on how Solution Snippets need to be reused, and such information would enhance the reusability of Solution Snippets. These limitations of datasets of pairs could adversely affect the quality of the code being generated by machine learning models. In this research, I conducted a qualitative study to categorize various presentations of Solution Snippets in SO’s answers as well as how Solution Snippets can be adapted for reuse. By doing so, I identified eight categories of how Solution Snippets are presented in SO’s answers and five categories of how Solution Snippets could be adapted. Based on these results, I concluded several potential reasons why it is not easy to create datasets of Question-Solution pairs. The first categorization informs that finding the correct location of the Solution Snippet is challenging when there are several code blocks within the answer to the question. Subsequently, the researcher must identify which code within that code block is the Solution Snippet. The second categorization informs that most Solution Snippets appear challenging to be adapted for reuse, and how Solution Snippets are potentially adapted is not explicitly stated in them. These insights shed light on creating better quality datasets from questions and answers posted on Stack Overflow. / Graduate

Les différents projets présentés dans cette thèse contribuent à la compréhension de plusieurs aspects clés de la circulation océanique. Le premier aspect que nous étudions porte sur les processus physiques à l'origine du mélange lié à la marée; deux processus ont été mis en évidence. Depuis la latitude critique vers l'équateur, la marée interne transfert son énergie à des ondes plus petite échelle via des instabilités triadiques résonnantes impliquant les ondes proche inertielles. Depuis la latitude critique vers le pôle, les ondes de marée interne continuent de transférer leur énergie à des ondes plus petite échelle, mais étonnamment ce transfert se fait entre la marée interne et des ondes évanescentes.Dans la deuxième étude, nous étudions l'effet d'un courant moyen sur la propagation et la dissipation des ondes de marée interne, générées à la topographie dans des simulations haute résolution. Dans ce cas, la dépendance en latitude de la dissipation de la marée interne est plus lisse et plus proche d'une constante. Ce changement de la dépendance en latitude peut être lié au décalage des fréquences des ondes de marée interne par effet Doppler, ce qui induit la génération d'ondes secondaires plus petite échelle.Dans la troisième étude, nous étudions l'effet d'une perturbation générée en amont sur la circulation dans le bassin amont dû à l'interaction entre la perturbation et un seuil hydrauliquement contrôlé. Les ondes de Kelvin et topographiques de Rossby, générées par une variation de l'afflux d'eau dans le bassin amont, perturbent l'écoulement au dessus du seuil et ainsi l'export d'eau. Cette perturbation est due à la réfraction des ondes sur le seuil à chaque passage, une fois qu'elles ont fait le tour du bassin amont. / The various projects presented in this thesis contribute to our understanding of various key aspects of the oceanic circulation. The first aspect that we investigate is the physical processes responsible for this tidal mixing, and we identify two processes. Equatorward of the critical latitude, internal tides transfer their energy to smaller-scale waves via triadic resonant instabilities involving near-inertial waves. Poleward of the critical latitude, internal tides still transfer energy to smaller-scale waves, but surprisingly this transfer takes place between the internal tide and evanescent waves.In the second study, we investigate the effect of a mean current on the propagation and the dissipation of internal tides generated at the topography in high-resolution simulations. In that case, the latitudinal dependence of the tidal energy dissipation is found to be smoother and closer to a constant. This change in the latitudinal dependence can be linked to the Doppler shift of the frequency of the internal tides, which impacts the generation of smaller-scale secondary waves.In the third study, we study the effect of an upstream disturbance on the upstream circulation by interaction with a hydraulically controlled sill. The Kelvin and topographic Rossby waves, generated by a change in the upstream inflow, perturb the flow through the channel and hence the water export. This perturbation is due to the refraction of the waves at the sill at each passage, once they go around the upstream basin.

No description available.

Utbyggnation av städer och allt större andel hårdgjorda ytor leder till problem med dagvattenhanteringen. Flödena blir snabbare samtidigt som större mängder än tidigare bildar avrinning och då är det viktigt att de befintliga systemen klarar av att hantera dem. Dagvatten från tak och hårdgjorda ytor och dräneringsvatten från källarfastigheter kan vara kopplat till spillvattennätet och leda till att vattenflödena i ledningarna vid stora regn kan bli betydligt större än de är dimensionerade för, med kapacitetsproblem som följd. En lösning som många VA-huvudmän har implementerat är att använda öppna dagvattenlösningar istället för att välja det mer kostnadskrävande alternativet att bygga ut ledningssystemet. Att koppla om stuprör, brunnar och dräneringsledningar och gräva diken för att leda om vattnet är både kostnads- och resurskrävande. Syftet var därför att undersöka om multikriterieanalys kan fungera som ett lämpligt verktyg för att allokera resurserna till de områden som ger mest nytta per satsad krona. Detta genom att ta fram en metodik för detta syfte och testa dess robusthet för att avgöra om den är lämplig att applicera eller om osäkerheterna i parametervärdena blir för stora för att några slutsatser ska kunna dras. Metodiken som togs fram testades på Bjursås, ett litet samhälle två mil utanför Falun, eftersom omfattande utredningar gjorts i området tidigare, vilket innebar att mycket data fanns att tillgå. Undersökningar gjordes av var mängderna kunde förväntas bli stora, var det fanns stor risk för källaröversvämningar och vilka områden som bidrog mest till bräddningar. Detta utvärderades tillsammans med förväntade åtgärdskostnader och en samlad bedömning gjordes av var nyttan per satsad krona bör bli störst. Stora osäkerheter återfanns i bedömningen. Slutsatsen blev att metoden kan fungera som stöd vid beslutsunderlag, men att den inte är tillräckligt robust för att kunna användas uteslutande utan att efterföljande utvärderingar och kritisk granskning av resultaten måste göras. Detta kan lämpligtvis ske genom en känslighetsanalys. För att resultaten ska utgöra ett användbart verktyg för VA-huvudmannen måste också kostnaderna utvärderas noggrannare än de har gjorts i den här studien. / Urbanization along with a greater amount of hardened surfaces affects the storm water management. When the flows get faster and larger amounts create runoff, it is crucial that the available systems are able to handle the water. Storm water from roofs and asphalt surfaces and drainage water can be connected to the sewage water pipelines and make the flows in the conduits at rainfall much greater than they are designed for, leading to capacity issues. Many municipalities have implemented open storm water solutions instead of choosing the more cost-ineffective way of expanding the conduit system. Reconnecting downspouts, wells and drainage pipelines and digging trenches to lead the water is both cost and resource demanding. Therefore the aim of this study was to investigate whether multi criteria analysis can be used as an appropriate tool in order to allocate the resources to the most beneficial areas. This was done by developing a method for this aim and testing its robustness in order to determine if it is suitable to use in this context or if the uncertainties make the method too unreliable. The robustness in the method developed can be questioned since the uncertainties can be substantial. To be able to use this method, a lot of data is needed and the method needs to be updated relatively often in order to contain relevant information. It is recommended that a sensitivity analysis is performed along with the method, since the use of only one set of parameters can make the result relatively arbitrary. Using a Monte Carlo procedure with the uncertainties defined can reduce the time needed to measure and identify the values. The sensitivity analysis showed that the parameters that have the largest impact on the results are the number of residents living in every real estate with a basement, the catchment areas, the roughness parameters of the pipelines and the use of energy and chemicals in the system. In the future, the urbanization is expected to increase as well as the amount of rainfall and problems related to inflow and infiltration are expected to become more common. The hope is that the method used and its results will be useful for the municipalities’ future planning and to inspire to more studies on this topic.

L’optimisation du système d’assainissement et la réduction des rejets d’eaux résiduaires urbaines non traitées est devenue un enjeu majeur pour de nombreuses collectivités dans le but d’atteindre les objectifs de qualité des milieux aquatiques fixés par la Directive Cadre européenne sur l’Eau (DCE 2000/60/CE). Pour cela, une parfaite connaissance du système d’assainissement est nécessaire. L’objectif de cette thèse, financée par la CDAPP et l’Agence de l’Eau Adour Garonne, était l’étude de la dynamique du système d’assainissement de la CDAPP et de sa contribution sur les flux de polluants dans le milieu récepteur (le Gave de Pau). La première étape du travail a été consacrée à la caractérisation hydraulique et physicochimique du système d’assainissement par temps sec et par temps de pluie. Une étude hydraulique a été tout d’abord réalisée et a permis de mieux appréhender la dynamique des déversements via les déversoirs d’orage (DO) en fonction de la nature des évènements pluvieux. D’autre part, la caractérisation physico chimique des eaux usées (matières en suspension ou MES, demande chimique en oxygène ou DCO, métaux, hydrocarbures aromatiques polycycliques) a mis en évidence que pour l’ensemble de ces paramètres, une nette augmentation des flux par temps de pluie était observée en particulier en début d’événement (augmentation d’un facteur de 2 à 10). Ce phénomène s’explique par l’apport de polluant par les eaux de ruissellement et l’érosion des dépôts accumulés par temps sec dans les réseaux. Seul l’azote total se comporte différemment puisqu’il est majoritairement présent sous forme dissoute. Afin de mieux appréhender la dynamique des paramètres polluants réglementaires (MES, DCO et azote), un suivi haute fréquence (au pas de temps de cinq minutes) a été mis en place durant un an à l’aide de sondes de turbidité et de conductivité. Ce suivi en continu constitue la troisième partie de ce travail. Des corrélations (r² ≈ 0,9) ont été établies entre d’une part, les paramètres polluants DCO et MES, et la turbidité et d’autre part, entre la conductivité et l’azote total. Ces enregistrements ont permis une meilleure compréhension du fonctionnement du système d’assainissement : mise en évidence du phénomène de first flush, estimation des flux polluants déversés via les DO, étude des phénomènes de stockage dans les réseaux. La dernière partie de cette thèse vise à l’étude de la contribution des rejets d’assainissement dans le milieu récepteur. Elle a permis de démontrer la contribution modérée du rejet de sortie de STEP (entre 1 et 15 %) par temps sec. Par temps de pluie, la contribution du système d’assainissement via les DO est extrêmement variable suivant les conditions hydro-climatiques (de < 1 % à plus de 50 %). Ce travail a permis d’une part d’apporter des résultats utilisables par le gestionnaire de l’assainissement pour optimiser la gestion des eaux usées de la CDAPP. D’autre part, ce travail apporte des résultats plus fondamentaux relatifs à une meilleure connaissance de la dynamique hydrologique et physicochimique des eaux résiduaires urbaines et des polluants associés tels que la mise en évidence, à l’aide d’outils statistiques, des paramètres influençant les déversements et les concentrations en polluants par temps de pluie. / Optimization of sewer system and reduction of untreated wastewater discharges has become a key issue for many communities in order to achieve the good quality of aquatic environments set by the European Framework Directive (WFD 2000/60/EC). For this, a perfect knowledge of sanitation is required. The objective of this thesis, funded by CDAPP and Adour Garonne Water Agency, was the study of the dynamics of the CDAPP sanitation and its contribution to the pollutants fluxes in the receiving environment (the river Gave de Pau). The first step of the work was devoted to the hydraulic and physicochemical wastewater characterization during dry and wet weather. A hydraulic study was first carried and helped to better understand the dynamics of discharges through the combined sewer overflow (CSO) according to the rainfall events characteristics. On the other hand, the physico-chemical characterization of wastewater (suspended solids or TSS, chemical oxygen demand or COD, metals, polycyclic aromatic hydrocarbons) showed that for all these parameters, a clear increase of pollutant fluxes was observed at the beginning of the rainfall event (increase by a factor of 2 to 10). This phenomenon is explained by the runoff contribution and erosion of sediments accumulated in the networks during dry weather periods. Only total nitrogen behaves differently because it’s mostly dissolved. To better understand the dynamics of pollutants parameters (TSS, COD and nitrogen), high frequency monitoring (every five minutes) has been established for one year with turbidity and conductivity sensors. This continuous monitoring is the third part of this work. Correlation functions (r² ≈ 0.9) were found between, the pollutant parameters COD and TSS, and turbidity, and secondly, between conductivity and total nitrogen. These records allowed a better understanding of sanitation system: highlighting the first flush phenomenon, estimation of pollutant loads discharged by CSO, study of storage networks phenomenon. The last part of this thesis aims to study the contribution of wastewater discharges to the receiving environment. It demonstrated the moderate contribution of rejection output STEP (between 1% and 15%) in dry weather. In rainy weather, the contribution of sanitation through CSO is extremely variable depending on the hydro-climatic conditions (<1% to over than 50%). This work has led to provide usable results for the sanitation manager to optimize CDAPP wastewater treatment. Moreover, this work provides most fundamental results for a better understanding of the hydrological and physicochemical dynamics of urban wastewater and associated pollutants such as highlighting, using statistical tools, the parameters influencing pollutant concentrations during rainfall events.

Ce travail constitue une étude préliminaire au développement d’un nouvel outil d’observation de la thermocline saisonnière de la Mer d’Iroise, la sismique réflexion. Une application inédite de cette technique à l’imagerie de structures océanographiques très peu profondes (z < 50 m) est réalisée. Dans un premier temps des règles de construction d’un dispositif sismique dédié à l’observation de telles cibles ont été définies à partir d’une réflexion théorique sur la mesure de sismique. Une évaluation de systèmes existants a ensuite été réalisée au travers de l’étude de 4 profils sismiques des campagnes GO, Carambar et Sigolo retraités spécifiquement, présentant des signaux aux mêmes profondeurs que la thermocline de l’Iroise. Ces dispositifs conventionnels apparaissent inadaptés à l’observation d’une cible océanographique superficielle, du fait i – d’un fort effet de filtre d’antenne lié à de grands offsets et longueurs de trace, et ii – de sources qui ne combinent pas puissance et fine résolution verticale. A partir de données océanographiques nouvelles acquises en Mer d’Iroise lors de la campagne Fromvar (été 2010), l’acquisition sismique a été modélisée, et les paramètres du dispositif idéal ajusté. Un système courts – offsets comprenant 4 flûtes de 6 traces de 1.8 m et un Sparker fournissant un signal de 400 Hz avec un niveau d’émission de 210 dB re 1 μPa @1m, a été proposé. Testé lors de la campagne ASPEX 2012, il a fournit une image de résolution latérale inédite de la thermocline saisonnière à 30 m de profondeur et de ses variations de fine échelle horizontale (quelques centaines de m à quelques km) causées par des ondes internes, au large de la Bretagne sud. / This work is a preliminary study for the development of a new tool, marine seismic reflection, for the observation of the seasonal thermocline of the Iroise Sea. It is the first application of this technique to the observation of shallow oceanographic structures (z < 50 m). In order to define general requirements for the design of a seismic acquisition system suited to the imaging of such targets, the theory of the seismic measurement was first investigated. Four multi-channel seismic reflection profiles from the GO, Carambar and Sigolo cruises were then reprocessed and analyzed in order to assess the potential of conventional seismic systems. They were found ill suited to the imaging of shallow oceanographic structures, because of a high antenna filter induced by large offsets and seismic trace lengths, and sources that do not reconcile with the high level of emission and fine vertical resolution. New oceanographic data acquired in the Iroise Sea during the Fromvar 2010 cruise allowed simulation of the seismic acquisition, and the definition of optimal acquisition parameters for the imaging of the seasonal thermocline. Sea trials of this specifically designed system were performed during the ASPEX survey, conducted in early summer 2012. The seismic device featured: four seismic streamers, each consisting of 6 traces of 1.80 m.; a 1000 J SIG Sparker source, providing a 400 Hz signal with a level of emission of 210 dB re 1 μPa @1m. This survey captured the 15 m thick, 30 m deep seasonal thermocline in unprecedented detail, showing images of vertical displacements of horizontal wavelength of a several hundreds m to a few km , most probably induced by internal waves.

Submitted by José Carlos Toledo Veniziani Junior (veniziani@gmail.com) on 2018-05-30T10:46:24Z No. of bitstreams: 1 Veniziani_Jr_J_C_T.pdf: 11360032 bytes, checksum: c6b48273852e5aad2d73183ee856e5ec (MD5) / Approved for entry into archive by Adriana Aparecida Puerta null (dripuerta@rc.unesp.br) on 2018-05-30T13:15:02Z (GMT) No. of bitstreams: 1 venizianijunior_jct_dr_rcla.pdf: 10933461 bytes, checksum: 13254f5586b981ff360e18d863f2ad6d (MD5) / Made available in DSpace on 2018-05-30T13:15:02Z (GMT). No. of bitstreams: 1 venizianijunior_jct_dr_rcla.pdf: 10933461 bytes, checksum: 13254f5586b981ff360e18d863f2ad6d (MD5) Previous issue date: 2018-04-13 / A disponibilidade da água é influenciada pelo comportamento sistêmico do ciclo hidrológico, do qual a vazão, a precipitação e a cobertura vegetal são importantes elementos. Devido às suas características espaciais, a bacia hidrográfica constitui uma unidade geográfica adequada para a realização de estudos ambientais e hidrológicos. As ferramentas de geoprocessamento forneceram suporte metodológico à realização destes estudos, facilitando a obtenção, a organização e a análise espacial. Esta tese analisou a relação entre as variáveis vazão, precipitação, e a densidade da cobertura vegetal, estimada através do índice de vegetação da diferença normalizada, (IVDN), para as sub-bacias hidrográficas dos rios Jacaré-Pepira e Jaú (SP). Também objetivou verificar a viabilidade do uso do IVDN como subsídio à gestão ambiental de bacias hidrográficas. Os resultados mostraram que existe correlação entre as variáveis precipitação, vazão e o IVDN, utilizado como um indicativo das características da cobertura vegetal. Esses resultados indicaram que as vazões médias e mínimas apresentaram maior correlação com o IVDN. Considerando os anos padrão climáticos, secos, chuvosos e habituais, foi possível perceber que nos anos secos esta correlação ficou mais evidente reforçando a compreensão de que maiores densidades de cobertura vegetal aumentam a infiltração e reduzem o escoamento superficial, garantindo uma maior disponibilidade de água para as demandas socioambientais locais. A dinâmica espaço-temporal do uso e ocupação das terras na bacia do Jacaré-Pepira era menos intensa e caracterizada principalmente por pastagens e silvicultura que não demandam ciclos de cultivo curtos. Enquanto que na Bacia do Rio Jaú a dinâmica era mais intensa, sobretudo por influência do cultivo de cana de açúcar que apresenta ciclos curtos de plantio e colheita. A precipitação e IVDN apresentaram dependência espacial na sub-bacia do rio Jacaré-Pepira, enquanto no rio Jaú esta dependência não foi verificada. Isto se deve ao fato de que a cobertura vegetal suprimida no período da colheita, não ser influenciada diretamente pelas precipitações, diminuindo a dependência espacial destas duas variáveis. Foi possível verificar que o IVDN representa um importante indicador da situação ambiental hidrológica local, podendo subsidiar a gestão ambiental de bacias hidrográficas. Essas constatações são importantes para a gestão dos recursos hídricos superficiais em bacias hidrográficas, evidenciando o impacto do uso das terras na cobertura vegetal e na vazão, interferindo diretamente na disponibilidade da água superficial para a sociedade. / The systemic behavior of the hydrological cycle, mainly flow, precipitation and vegetation cover influence the availability of water. The watershed is the appropriate geographic unit for environmental and hydrological studies. Geographic Information Systems (GIS), and remote sensing, helping to carry out hydrological studies, making it easier to obtain, organize, and analyze data. The objective of this research was to characterize the main environmental aspects and analyze the relation among flow rate, rainfall, and the vegetation cover variables, estimated by the normalized difference vegetation index (NDVI), for the sub-basins of the Jacaré-Pepira and Jaú rivers (SP). It was also possible to check the viability to use NDVI to manage the environmental conditions of watershed. These results indicated that the average and minimum flows are the variables that showed the highest correlation with the NDVI in both areas. In the dry standard years, the correlation between the IVDN and the flow were more evident. This situation showed that greater intensities of vegetal cover intensify the infiltration and reduce the surface runoff, offering a greater availability of water for the local socio-environmental processes. The dynamics of land use in Jacaré-Pepira was less intense and characterized mainly by pasture and silviculture that do not require short crop cycles. While in Jaú the dynamics were more intense, mainly to the influence of sugarcane cultivation, which presents short crop cycles. The variables precipitation and NDVI showed spatial dependence in the Jacaré-Pepira, while in Jaú the dependence was not present. This situation evidenced that the rainfall spatial distribution demonstrated by the coefficient of variation promotes greater impacts in areas where the dynamics of land use is more intense. This situation occurs because the suppressed vegetation in the harvest, by the anthropic action, is not influenced directly by the rains, reducing the spatial dependence of these two variables. The NDVI can be considered an important indicator of the local hydrological environmental situation and subsidize the environmental management of watersheds. It is important for the management of surface water resources, showing how land use and its consequent impact on vegetation cover can influence flow rate, and interfere in the accessibility of surface water to society.

In this thesis, by being motivated from the challenges in perinatal networks, we address design, evaluation and flow control of a stochastic healthcare network where there exist multiple levels of hospitals and different types of patients. Patients are supposed urgent; thus they can be rejected and overflow to another facility in the same network if no service capacity is available at their arrival. Rejection of patients due to the lack of service capacity is the common phenomenon in overflow networks. We approach the problem from both strategic and operational perspectives. In strategic part, we address a location & capacity planning problem for adjusting the network to better meet demographic changes. In operational part, we study the optimal patient admission control policies to increase flexibility in allocation of resources and improve the control of patient flow in the network. Finally, in order to evaluate the performance of the network, we develop new approximation methodologies that estimate the rejection probabilities in each hospital for each arriving patient group, thus the overflow probabilities among hospitals. Furthermore, an agent-based discrete-event simulation model is constructed to adequately represent our main applicationarea: Nord Hauts-de-Seine Perinatal Network. The simulation model is used to evaluate the performance of the complex network and more importantly evaluate the strength of the optimal results of our analytical models. The developed methodologies in this thesis are combined in a decision support tool, foreseen under the project "COVER", which aims to assist health system managers to effectively plan strategic and operational decisions of a healthcare network and evaluate the performance of their decisions.

Les bassins périurbains, constitués de zones urbaines, agricoles et naturelles, sont des bassinsversants complexes à étudier. L’augmentation des surfaces imperméables et les modifications deschemins d’écoulement par les réseaux d’assainissement influencent leur hydrologie. Ces modificationssont notamment liées aux choix de modes de gestion des eaux pluviales : réseaux unitaires,réseaux séparatifs, infiltration à la parcelle, etc. La modélisation hydrologique spatialisée, quirend compte de l’hétérogénéité des bassins versants, est un outil permettant d’évaluer les différentsenjeux en termes d’occupation du sol et de gestion des eaux pluviales. Cependant, peu demodèles ont été construits pour être appliqués aux bassins périurbains, à l’échelle des gestionnaires(˜ 100 km2) et pour des simulations sur de longues périodes (> 10 ans). La modélisationhydrologique doit donc être adaptée afin de mieux capter les spécificités des milieux périurbainstelles que l’hétérogénéité de l’occupation du sol et la connexion de certaines zones urbaines à unréseau d’assainissement.Ce travail de thèse a consisté à développer un nouvel outil de modélisation adapté à ces problématiques: le modèle distribué horaire J2000P. Ce modèle simule les processus hydrologiquesen milieux ruraux et urbains et prend en compte les réseaux d’assainissement, les connexionsà ces réseaux et les déversements des déversoirs d’orage (DO). Le modèle a été mis en oeuvresur le bassin périurbain de l’Yzeron (˜ 130 km2), situé à l’ouest de Lyon. L’évaluation, effectuéeà l’exutoire de différents sous-bassins de tailles et d’occupations du sol différentes, montre desrésultats très encourageants. Le modèle a tendance à sous-estimer le débit mais la dynamiquedes pics est bien représentée tout comme le déversement des DO. Suite aux résultats de l’évaluation,une analyse de sensibilité « pas à pas » du modèle a été réalisée et différentes hypothèsesde fonctionnement du bassin ont été formulées pour améliorer la compréhension du modèle etdes processus représentés. Le modèle a ensuite été utilisé pour tester l’impact de modificationsde l’occupation des sols et/ou de la gestion des eaux pluviales sur la réponse hydrologique. Lemodèle montre que la gestion de l’occupation du sol a moins d’influence sur l’hydrologie dubassin que la gestion du réseau d’assainissement. / Growing urbanization and related anthropogenic processes have a high potential to influencehydrological process dynamics. Typical consequences are an increase of surface imperviousnessand modifications of water flow paths due to artificial channels and barriers (combined and separatedsystem, sewer overflow device, roads, ditches, etc.). Periurban catchments, at the edgeof large cities, are especially affected by fast anthropogenic modifications. They usually consistof a combination of natural areas, rural areas with dispersed settlements and urban areas mostlycovered by built zones and spots of natural surfaces. Spatialized hydrological modeling tools, simulatingthe entire hydrological cycle and able to take into account the important heterogeneityof periurban watersheds can be used to assess the impact of stormwater management practiceson their hydrology.We propose a new modeling tool for these issues : the hourly distributed J2000P model.This model simulates the hydrological processes in rural and urban areas and takes into accountthe sewerage networks, connections to these networks and overflows from sewer overflow devices(SOD). The application site is the Yzeron catchment (˜ 130 km2), located in the West of Lyon.The evaluation, conducted at the outlet of different sub-basins with different sizes and landuse, shows very encouraging results. The model tends to underestimate the discharge but thedynamics of the peaks and the SOD overflows are well simulated. The model is also used to testthe impact of changes in land use and/or stormwater management on the hydrological response.The results show that land use management has less impact on the hydrology of the catchmentthan stormwater management.