O termo silicose refere-se ao processo de fibrose pulmonar causado pela inalação de poeira contendo sílica. É uma doença ocupacional, incurável, que se inicia nas vias aéreas distais e pode progredir independente do término da exposição. Os testes de função pulmonar, apesar de não serem utilizados como ferramenta diagnóstica para silicose, são amplamente empregados para acompanhar longitudinalmente esses indivíduos. Estudos recentes sugerem que a Técnicas de Oscilações Forçadas (FOT) pode ser aplicada para detecção de alterações pulmonares precoces em indivíduos com silicose. Contudo, existem poucos estudos descrevendo as alterações de mecância respiratória associada com a silicose através da FOT. Neste contexto, os objetivos deste estudo são: (1) analisar as alterações de mecânica respiratória de indivíduos portadores de silicose com diferentes graus de obstrução e (2) avaliar a capacidade da FOT em detectar alterações na função pulmonar decorrentes da silicose. Trata-se de um estudo transversal controlado com avaliação de casos prevalentes, tendo como unidade de avaliação o indivíduo. Os exames realizados incluíram medidas de espirometria e FOT. Foi selecionado um total de 67 indivíduos, 46 portadores de silicose e 21 sadios, caracterizando o grupo controle. Os indivíduos com diagnóstico de silicose foram divididos em três grupos classificados de acordo com o nível de obstrução sugerido pela espirometria. Essa classificação resultou em três categorias: Indivíduos normais ao exame espirométrico (NE), n= 12; com distúrbio ventilatório obstrutivo leve (DVOL), n=22; com distúrbio ventilatório obstrutivo moderado ou acentuado (DVOMA), n= 12. Todos os indivíduos realizaram exames da FOT para análise das propriedades resistivas e reativas do sistema respiratório. Posteriormente aos exames da FOT os indivíduos foram submetidos à espirometria. Considerando os grupos divididos a partir da espirometria, os parâmetros resistivos e reativos e a impedância do sistema respiratório em 4Hz (Z4Hz) se modificaram significativamente com a progressão da distúrbio obstrutivo. Na análise do poder diagnóstico da FOT os parâmetros R0, Rm, Rsr4 e |Z4Hz| mostraram-se precisos para identificar as modificações de mecânica respiratória em pacientes com silicose apresentando distúrbio ventilatório obstrutivo leve. Para distúrbio ventilatório obstrutivo moderado e acentuado todos os parâmetros analisados apresentaram habilidade para identificar essas alterações. Na análise entre o grupo controle e normal ao exame, nenhum parâmetro da FOT apresentou valor de acurácia adequado para uso clínico. Esses resultados são coerentes com as alterações fisiopatológicas relacionadas à silicose, confirmando o potencial da FOT na avaliação das modificações de mecânica respiratória em doentes com silicose. / The term silicosis is the name given to the pulmonary fibrosis caused by inhalation of dust containing crystalline silica. Is a typical occupational disease, chronic, incurable, starting in the peripheral airways and that can progress independently of the end of exposure. The pulmonary function tests, although not used as a diagnostic tool for silicosis, are widely employed to follow these individuals. Recent works suggests that the Forced Oscilation Technique (FOT) may be applied in the detection of early respiratory changes in silicosis. However, few studies have been analyzing the changes on respiratory mechanics associated with silicosis through the FOT. In this context, the aims of this study were (1) to analyze changes respiratory mechanics in subjects with silicosis with different degrees of obstruction by FOT, and (2) to evaluate the potential of the FOT to detect alterations in the lung function resulting from silicosis. This is a sectional study evaluation of prevalent cases, with the evaluation unit the individual. The examinations included measurement of FOT and spirometry. Sixty-seven volunteers were analyzed: 21 healthy subjects and 46 with silicosis. Spirometry was used to classify airway obstruction in the silicosis groups. This classification resulted in three categories: normal spirometric exam (n = 12); mild obstruction (n = 22); moderate or severe obstruction (n = 12.). All subjects performed FOT exam for the analysis of resistive and reactive properties of the respiratory system. The order of the examinations was FOT, followed by spirometry. Considering the groups classified according to the spirometry, the resistive and reactive the parameters and the impedance of the respiratory system at 4Hz (|Z4Hz|), have changed significantly with the progression of obstructive. The analysis of the diagnostic power of FOT parameters R0, Rm, and Rsr4 |Z4Hz| showed to be accurate to identify the changes of respiratory mechanics in silicosis patients with mild obstructive lung disease. To the moderate and severe obstructions, all the parameters analyzed showed adequate to identify these changes. In the analysis between the control and normal exam, no parameters of the FOT showed adequate measure to use to correctly identify these subjects. The FOT parameters adequately described the pathophysiological changes associated with silicosis and presented adequate accuracy for clinical use, indicating that this technique can be helpful in the evaluation respiratory mechanics in this disease.

In this thesis, the role of mid-latitude cyclones in air pollution transport in the Northern Hemisphere is quantified. The storm tracking model, TRACK, is used to study the mechanisms through which pollution, specifically ozone (O3) and carbon monoxide (CO), are vented from the boundary layer to the free troposphere and thus transported over large distances, as well as the introduction of O3 from the stratosphere into the troposphere. The relationship between mid-latitude cyclones and air pollution transport of O3 and CO is explored for the first time using the Monitoring Atmospheric Composition and Climate (MACC) reanalysis, a combined meteorology and composition reanalysis dataset. A comparison between springtime surface ozone measurements at rural background sites on the west coast of Europe and cyclone track frequency in the surrounding regions was used to first establish the correlation between cyclone location and surface air quality. The focus is on spring as it tends to be the season of maximum intercontinental transport of O3. The surface observations were compared to the MACC O3 values at the same locations and case studies of how cyclones can influence surface O3 measurements are described. When cyclones track north of 53°N, there is a significant probability that the surface O3 will be high (> the 75th percentile), due to the close proximity to stratospheric intrusions and the transport at low levels across the North Atlantic Ocean. The most intense spring cyclones (95th percentile) were selected for two regions, the North Atlantic and the North Pacific, for further investigation into the mechanisms which impact O3 and CO concentrations near cyclones. These intense cyclones ( 60 over each region) often tracked over the major emission sources of eastern North America and East Asia. The distributions of MACC O3 and CO within a "typical" intense cyclone are examined by compositing the cyclones together. The cyclone-centered composites were compared to background composites of "average conditions" created by sampling the reanalysis data of the previous year to the cyclone locations. Mid-latitude cyclones are found to redistribute concentrations of O3 and CO horizontally and vertically throughout the cyclone. This is clearly shown to occur through two main mechanisms: (1) vertical lifting of CO-rich and O3-poor air isentropically from near the surface to the mid- to upper-troposphere in the region of the warm conveyor belt; and (2) descent of O3-rich and CO-poor air isentropically in the vicinity of the dry intrusion, from the stratosphere toward the mid-troposphere. This work was expanded to identify the links between teleconnection patterns, mainly the North Atlantic Oscillation (NAO), that affect the major storm track pathways in the North Atlantic sector and the distribution of MACC O3 and CO throughout the troposphere and lower stratosphere. For this analysis, TRACK was used to calculate seasonal weighted-average O3 and CO distribution maps based on the monthly NAO index. During positive NAO phase, the persistence of low pressures over the North Atlantic coupled with the Azores High promotes transport across the North Atlantic throughout the troposphere. During negative NAO phase, blocking high pressure in the eastern North Atlantic are known to occur, which shifts transport pathways to a more southerly zonal flow. This work demonstrates the complex relationship between the horizontal and vertical distribution of pollution, including surface concentrations, and synoptic-scale systems.

Les ganglions de la base (GB) sont principalement connus pour leurs fonctions motrices, mais présentent également des fonctions non motrices. Sans surprise, il a été montré qu’ils sont impliqués dans des troubles moteurs tels que la maladie de Parkinson ou les dystonies. Des études récentes suggèrent que les GB jouent également un rôle prépondérant dans des maladies “non-motrices” telles que l’épilepsie d’absence , qui est une épilepsie généralisée non convulsive. Dans l’ensemble de ces dysfonctions des GB, les symptômes sont accompagnés de différents patrons oscillants d’activité neuronale souvent synchronisés entre les différents noyaux des GB, le cortex et d’autres aires cérébrales. Comment les GB peuvent-ils favoriser ou soutenir ces différentes activitées oscillantes?Des expériences récentes ont montré le rôle clé joué par les GB dans l’épilepsie d’absence et remettent en question le point de vue traditionnel selon lequel les circuits thalamo-corticaux sont responsables des crises d’absence. Nous proposons une nouvelle théorie selon laquelle les rétroactions opérées par les GB sur l’activité corticale rend le réseau bistable et entraîne les patrons d’activité oscillante qui apparaîssent pendant les crises. Notre théorie est compatible avec l’ensemble des résultats expérimentaux connus et elle prédit qu’un input excitateur transitoire sur le cortex peut terminer prématurément les crises d’absence. Nous présentons ici des résultats préliminaires en accord avec cette prédiction.De multiples fréquences des oscillations d’activité sont observées dans la maladie de Parkinson au sein des GB, telles que les fréquences correspondant aux tremblement des membres ou encore les oscillations béta. Nous montrons que notre model peut générer des oscillations à différentes échelles temporelles qui coïncident avec les fréquences des oscillations dans la maladie de Parkinson. Notre théorie peut rendre compte des oscillations observées dans la maladie de Parkinson et dans l’epilépsie d’absence dans un cadre théorique unifié et suggère deux scénarios pour expliquer les multiples fréquences des oscillations d’activité, à la fois pathologiques et fonctionnelles. / The Basal Ganglia (BG) are thought to be involved primarily in motor but also in non-motor functions. Unsurprisingly, the BG are shown to be involved in motor dysfunctions such as Parkinson's disease or dystonia. More recent studies suggest the key role of the BG in "non-motor" diseases such as absence epilepsy which is a generalized non-convulsive epilepsy. In these diseases, symptoms accompany various oscillatory patterns of neural activity often synchronized across the BG, cortex and other brain areas. How can the BG support these different kinds of oscillatory patterns?Recent experiments have highlighted the key role of the BG in absence seizures and question the traditional view in which thalamocortical circuits underlie absence seizures. We propose a novel theory according to which the feedbacks of cortical activity through BG make this network bistable and drive the oscillatory patterns of activity occurring during the seizures. Our theory is compatible with virtually all known experimental results and it predicts that well-timed transient excitatory inputs to the cortex advance the termination of absence seizures. We report preliminary experimental results consistent with this prediction.Multiple oscillatory frequencies are observed in Parkinsonian BG such as the frequencies of the limb tremor and the beta oscillations. We show that our model can generate oscillations with multiple timescales which resemble Parkinsonian oscillations. Our theory can model the oscillations in Parkinson's disease and absence epilepsy in a unified framework and points to two scenarios to explain multiple frequencies of pathological and functional oscillations.

Philosophiae Doctor - PhD / Numerical approximations of multiscale problems of important applications in ecology are investigated. One of the class of models considered in this work are singularly perturbed (slow-fast) predator-prey systems which are characterized by the presence of a very small positive parameter representing the separation of time-scales between the fast and slow dynamics. Solution of such problems involve multiple scale phenomenon characterized by repeated switching of slow and fast motions, referred to as relaxationoscillations, which are typically challenging to approximate numerically. Granted with a priori knowledge, various time-stepping methods are developed within the framework of partitioning the full problem into fast and slow components, and then numerically treating each component differently according to their time-scales. Nonlinearities that arise as a result of the application of the implicit parts of such schemes are treated by using iterative algorithms, which are known for their superlinear convergence, such as the Jacobian-Free Newton-Krylov (JFNK) and the Anderson’s Acceleration (AA) fixed point methods.

This research study is the result of a 3 years CIFRE PhD thesis between the Airbus design office(Aircraft Control domain) and TéSA laboratory in Toulouse. The main goal is to propose, developand validate a software solution for the detection and diagnosis of a specific type of elevator andrudder vibration, called limit cycle oscillation (LCO), based on existing signals available in flightcontrol computers on board in-series aircraft. LCO is a generic mathematical term defining aninitial condition-independent periodic mode occurring in nonconservative nonlinear systems. Thisstudy focuses on the LCO phenomenon induced by mechanical freeplays in the control surface ofa civil aircraft. The LCO consequences are local structural load augmentation, flight handlingqualities deterioration, actuator operational life reduction, cockpit and cabin comfort deteriorationand maintenance cost augmentation. The state-of-the-art for freeplay induced LCO detection anddiagnosis is based on the pilot sensitivity to vibration and to periodic freeplay check on the controlsurfaces. This study is thought to propose a data-driven solution to help LCO and freeplaydiagnosis. The goal is to improve even more aircraft availability and reduce the maintenance costsby providing to the airlines a condition monitoring signal for LCO and freeplays. For this reason,two algorithmic solutions for vibration and freeplay diagnosis are investigated in this PhD thesis. Areal time detector for LCO diagnosis is first proposed based on the theory of the generalized likeli hood ratio test (GLRT). Some variants and simplifications are also proposed to be compliantwith the industrial constraints. In a second part of this work, a mechanical freeplay detector isintroduced based on the theory of Wiener model identification. Parametric (maximum likelihoodestimator) and non parametric (kernel regression) approaches are investigated, as well as somevariants to well-known nonparametric methods. In particular, the problem of hysteresis cycleestimation (as the output nonlinearity of a Wiener model) is tackled. Moreover, the constrainedand unconstrained problems are studied. A theoretical, numerical (simulator) and experimental(flight data and laboratory) analysis is carried out to investigate the performance of the proposeddetectors and to identify limitations and industrial feasibility. The obtained numerical andexperimental results confirm that the proposed GLR test (and its variants/simplifications) is a very appealing method for LCO diagnostic in terms of performance, robustness and computationalcost. On the other hand, the proposed freeplay diagnostic algorithm is able to detect relativelylarge freeplay levels, but it does not provide consistent results for relatively small freeplay levels. Moreover, specific input types are needed to guarantee repetitive and consistent results. Further studies should be carried out in order to compare the GLRT results with a Bayesian approach and to investigate more deeply the possibilities and limitations of the proposed parametric method for Wiener model identification.

As a global climate phenomenon, the El Ni??o-Southern Oscillation (ENSO) involves the coupling of the ocean and the atmosphere. Most climate prediction studies have, by far, only investigated the teleconnections between global climatic anomalies and the ???surface??? predictors of ENSO. The prediction models resulting from these studies have generally suffered from inadequate, if not the lack of, skill across the so-called boreal ???spring barrier???. This is illustrated in the first part of this thesis where the applicability of the SOI phase for long-lead rainfall projections in Australia is discussed. With the increasing availability of subsurface ocean temperature data, the characteristics of the Pacific Ocean???s heat content and its role in ENSO are now better understood. The second part of this thesis investigated the predictability of ENSO using the thermocline as a predictor. While the persistence and SST-based ENSO hindcasts dropped in skill across the spring barrier, the thermocline-based hindcasts remained skillful even up to a lag of eighteen months. Continuing on the favorable results of ENSO prediction, the third part of this thesis extended the use of the thermocline in the prediction of Australia???s rainfall and streamflow. When compared to models that use ???surface??? predictors, the model that incorporated thermocline information resulted in more skillful projections of rainfall and streamflow especially at long lead-times. More importantly, significant increases in skill of autumn and winter projections demonstrate the ability of the subsurface ocean to retain some climatic memory across the predictability barrier. This resilience can be attributed to the high persistence of the ocean heat content during the first half of the year. Based on weighting, the model averaging exercise also affirmed the superiority of the ???subsurface??? model over the ???surface??? models in terms of streamflow projections. The encouraging findings of this study could have far-reaching implications not only to the science of ENSO prediction but also to the more pragmatic realm of hydrologic forecasting. What this study has demonstrated is an alternative predictor that is suitable for the long range forecasting of ENSO, rainfall and streamflow. With better hydrologic forecasting comes significant improvement in the management of reservoirs which eventually leads to an increase in the reliability and sufficiency of water supply provision.

Abstract not available

Background: Measurements of lung function are routinely used in patients with cystic fibrosis (CF) to provide information that may be clinically relevant. Spirometry is the conventional lung function measurement used, however young children find spirometry difficult to perform and often cannot achieve the strict acceptability criteria for the test. The forced oscillation technique (FOT) is a lung function measurement that only requires tidal breathing and is easy for young children to perform. However, there is limited information about the utility of this technique in the clinical assessment of young children with CF who are unable to perform spirometry. Aims: The aim of this project was to evaluate the FOT for clinical assessment in 2 to 7 year old children with CF. Specifically this involved: 1. Technical assessment of the FOT in children with CF; 2. Comparisons of lung function using the FOT in children with CF and healthy children; 3. Evaluation of associations with factors known to be associated with lung disease including: i) inflammation ii) infection and iii) structural damage. Methods Lung function was measured in a cohort of 59 children between the ages of 2 and 7 years with CF at the time of quarterly clinic visits. Resistance and reactance at 6, 8 and 10Hz (Rrs6, Rrs8, Rrs10, Xrs6, Xrs8, Xrs10, respectively) were reported and expressed as Z scores. Children were classified as asymptomatic or symptomatic based on a respiratory questionnaire and physical examination at the time of testing. Bronchoalveolar lavage and high resolution computed tomography (HRCT) were performed annually under general anaesthesia annually. BAL fluid was assessed for the presence of micro-organisms and quantification of a range of inflammatory markers and HRCT used to determine the extent of structural abnormalities. Results: The between test repeatability (n=25) for lung function was within limits previously described in healthy children. No systematic bias was observed and repeatability was not affected by the presence of respiratory symptoms. Children with CF (n=57) had significantly increased Rrs6-10 (p<0.0001) and decreased Xrs6-10 (p<0.004) compared to healthy children. Rrs6 and Xrs6-10 were significantly worse in the presence of respiratory symptoms, and Rrs6-10 progressively worsened from an asymptomatic to a symptomatic clinic visit. Children with CF (n=48) had no greater bronchodilator response (BDR) compared to healthy children. BDR was not influenced by the presence of an infection or respiratory symptoms. No relationships between inflammatory markers and lung function (n=39) were identified when the presence of an infection was adjusted for. Children with a current infection (n=20) had increased Rrs6-10 (p<0.01) and decreased Xrs6-10 (p<0.04) compared to children who were uninfected (n=23). These relationships were most marked for children infected with Pseudomonas aeruginosa, with children having a reduced lung function between 0.95 and 1.47 of a Z score. No relationships with the presence or absence of mild structural abnormalities (bronchiectasis, bronchial wall thickening and air trapping) and lung function at the time of HRCT were identified (n=34). Conclusion: The FOT is a repeatable measurement of lung function in children with CF and reliable results can be obtained in children as young as 2 years old. Young children with CF exhibit altered respiratory function which was affected by the presence of factors known to be associated with lung disease. The FOT has the potential to provide useful information about changes in clinical status in young children with CF and may be used to direct management of patient lung disease.

Cette thèse aborde un problème de transport appelé le Problème de m-Tournées Sélectives (PmTS) ou ”Team Orienteering Problem” en anglais. Le PmTS consiste à construire m tournées pour une flotte de véhicules afin de desservir un sous-ensemble sélectionné de clients. Dans le PmTS un service est fourni à chaque client visité en contrepartie de quoi, un gain est récolté. La tournée de chaque véhicule part d'un dépôt, passe par un sous-ensemble de clients et revient en un autre sans dépasser la longueur maximale autorisée. Chaque client peut être desservi au plus une fois par un unique véhicule. L'objectif est de maximiser le gain total récolté. Le PmTS étant un problème NP-difficile, notre objectif de recherche a consisté à proposer des heuristiques basées sur le principe général de ”Cluster first - Route second”. Ces algorithmes sont prévus pour être intégrés dans un logiciel de planification des tournées de techniciens de maintenance.

L'expérience OPERA (Oscillation Project with Emulsion t-Racking Apparatus) se propose de vérifier les résultats de Super-Kamiokande, tout en détectant l'apparition de neutrino tau dans un faisceau originellement "pur" en neutrino muonique, révélée par la topologie caractéristique de la désintégration du tau. La cible d'OPERA est constituée de murs de briques qui sont une alternance de feuilles de plomb et d'émulsions. Les émulsions sont des trajectographes de grande précision (~1 micron) qui vont être utilisés en masse lors de l'expérience et leur analyse nécessite un système de scan automatisé dédié. Tout d'abord, cette thèse a consisté en la participation à la mise en place du premier laboratoire de scan en France. La précision obtenue est conforme aux exigences de l'expérience et la rapidité demandée sera atteinte dans quelques mois. Ensuite, la séparation des pions et des muons à basse énergie a étudiée. Les premiers résultats, montrant la possibilité d'une telle séparation, ont été exposés. Enfin, un programme de reconstruction de ces particules en fin de parcours a été développé et testé, tenant compte des performances de scan auparavant étudiées.