Introdução: A Síndrome do Desconforto Respiratório Agudo (SDRA) apresenta alta incidência e mortalidade em pacientes de terapia intensiva. A ventilação mecânica é o principal suporte para os pacientes que apresentam-se com SDRA, entretanto ainda existe muito debate sobre a melhor estratégia ventilatória a ser adotada, pois a ventilação mecânica pode ser lesiva aos pulmões e aumentar a mortalidade se mal ajustada. Um dos principais mecanismos de lesão pulmonar induzida pela ventilação é o uso de volumes correntes altos, havendo evidência na literatura que a utilização de volumes correntes menores fornece uma ventilação dita protetora, a qual aumenta a probabilidade de sobrevivência. Objetivo: Explorar se uma estratégia ventilatória de alta frequência com pressão positiva (HFPPV) realizada através de um ventilador mecânico convencional (Servo-300) é capaz de permitir uma maior redução do volume corrente e estabilização da PaCO2 em um modelo de SDRA severa, inicialmente ventilado com uma estratégia protetora. Métodos: Estudo prospectivo, experimental que utilizou oito porcos que foram submetidos a uma lesão pulmonar através de lavagem pulmonar com soro fisiológico e ventilação mecânica lesiva. Em seguida, os animais foram ventilados com um volume corrente de 6 mL/kg, seguido de uma randomização de sequências diferentes de frequências respiratórias (30, 60, 60 com pausa inspiratória de 10 e 30%, 90, 120, 150, 60 com manobra de recrutamento alveolar mais titulação da PEEP e HFOV com 5 Hertz), até obter estabilização da PaCO2 entre 57 63 mmHg por 30 minutos. O ventilador Servo-300 foi utilizado para HFPPV e o ventilador SensorMedics 3100B utilizado para fornecer a ventilação oscilatória de alta frequência (HFOV). Dados são apresentados como mediana [P25th,P75th]. Principais Resultados: O peso dos animais foi de 34 [29,36] kg. Após a lesão pulmonar, a relação P/F, o shunt pulmonar e a complacência estática dos animais ficaram em 92 [63,118] mmHg, 26 [17,31] % e 11 [8,14] mL/cmH2O respectivamente. O PEEP total usado foi de 14 [10,17] cmH2O durante o experimento. Da frequência respiratória de 35 (e com volume corrente de 6 mL/kg) até a frequência ventilatória de 150 rpm, a PaCO2 foi 81 [78,92] mmHg para 60 [58,63] mmHg (P=0.001), o volume corrente (VT) progressivamente caiu de 6.1 [5.9,6.2] para 3.8 [3.7,4.2] mL/kg (P<0.001), a pressão de platô de 29 [26,30] para 27 [25,29] cmH2O (P=0.306) respectivamente. Não houve nenhum comprometimento hemodinâmico ou da oxigenação, enquanto os animais utilizaram a FiO2 = 1. Conclusões: Utilizando-se de uma ventilação mecânica protetora, a estratégia de HFPPV realizada com um ventilador mecânico convencional em um modelo animal de SDRA severa permitiu maior redução do volume corrente, bem como da pressão de platô. Esta estratégia também permitiu a manutenção de PaCO2 em níveis clinicamente aceitáveis / Introduction: Acute respiratory distress syndrome (ARDS) has a high incidence and mortality between critical ill patients. The mechanical ventilation is the most important support for these patients with ARDS. However, until now there is an important debate about how is the best ventilatory strategy to use, because the mechanical ventilation if not well set can cause lung injury and increase mortality. The use of high tidal volume is one of the most important mechanics of ventilation induced lung injury and there is evidence in the literature that using low tidal volume is a protective ventilation with better survival. Objective: To explore if high frequency positive pressure ventilation (HFPPV) delivered by a conventional ventilator (Servo-300) is able to allow further tidal volume reductions and to stabilize PaCO2 in a severe acute respiratory distress syndrome (ARDS) model initially ventilated with a protective ventilation. Methods: A prospective and experimental laboratory study where eight Agroceres pigs were instrumented and followed by induction of acute lung injury with sequential pulmonary lavages and injurious ventilation. Afterwards, the animals were ventilated with a tidal volume of 6 mL/kg, followed by a randomized sequence of respiratory rates (30, 60, 60 with pauses of 10 and 30% of the inspiratory time, 90, 120, 150, 60 with alveolar recruitment maneuver and PEEP titration and 5 Hertz of HFOV), until PaCO2 stabilization between 57 63 mmHg for 30 minutes. The Servo-300 ventilator was used for HFPPV and the ventilator SensorMedics 3100B was used for HFOV. Data are shown as median (P25th,P75th). Measurements and Main Results: Animals weight was 34 [29,36] kg. After lung injury, the P/F ratio, pulmonary shunt and static compliance of animals were 92 [63,118] mmHg, 26 [17,31] % and 11 [8,14] mL/cmH2O respectively. The total PEEP used was 14 [10,17] cmH2O throughout the experiment. From the respiratory rates of 35 (while ventilating with 6 mL/kg) to 150 breaths/ minute, the PaCO2 was 81 [78,92] mmHg and 60 [58,63] mmHg (P=0.001), the tidal volume progressively felt from 6.1 [5.9,6.2] to 3.8 [3.7,4.2] mL/kg (P<0.001), the plateau pressure was 29 [26,30] and 27[25,29] cmH2O (P=0.306) respectively. There were no detrimental effects in the hemodynamics and blood oxygenation, while the animals were using a FiO2 = 1. Conclusions: During protective mechanical ventilation, HFPPV delivered by a conventional ventilator in a severe ARDS swine model allows further tidal volume reductions. This strategy also allowed the maintenance of PaCO2 in clinically acceptable levels

This collection of essays examines the topic of macroeconomic stabilisation in an international context, focusing on monetary policy, capital controls and exchange rates. Chapter 1, written in collaboration with Giancarlo Corsetti and Joao Duarte, reconsiders the effects of common monetary policy shocks across countries in the euro area, using a data-rich factor model and identifying shocks with high-frequency surprises around policy announcements. We show that the degree of heterogeneity in the response to shocks, while being low in financial variables and output, is significant in consumption, consumer prices and macro variables related to the labour and housing markets. Mirroring country-specific institutional and market differences, we find that home ownership rates are significantly correlated with the strength of the housing channel in monetary policy transmission. We document a high dispersion in the response to shocks of house prices and rents and show that, similar to responses in the US, these variables tend to move in different directions. In Chapter 2, I build a two-country, two-good model to examine the welfare effects of capital controls, finding that under certain circumstances, a shut-down in asset trade can be a Pareto improvement. Further, I examine the robustness of the result to parameter changes, explore a wider set of policy instruments and confront computational issues in this class of international macroeconomic models. I document that within an empirically relevant parameter span for the trade elasticity, the gains from capital controls might be significantly larger than suggested by previous contributions. Moreover, I establish that a refined form of capital controls in the shape of taxes and tariffs cannot improve upon the outcome under financial autarky. Finally, results show that the conjunction of pruning methods and endogenous discount factors can remove explosive behaviour from this class of models and restore equilibrating properties. In Chapter 3, I use a panel of 20 emerging market currencies to assess whether a model that combines fundamental and non-fundamental exchange rate forecasting approaches can successfully predict risk premia (i.e. currency excess returns) over the short horizon. In doing so, I aim to overcome three main shortcomings of earlier research: i) Sensitivity to the chosen sample period; ii) seemingly arbitrary selection of explanatory variables that differs from currency to currency; and iii) difficulty in interpreting forecasts beyond the numerical signal. Based on a theoretical model of currency risk premia, I use real exchange rate strength combined with indicators for carry, momentum and economic sentiment to homogeneously forecast risk premia across all 20 currencies in the sample at a monthly frequency. In doing so, the model remains largely agnostic about structural choices, keeping arbitrarily imposed restrictions to a minimum. Results from portfolio construction suggest that returns are significant and robust both across currencies as well as over time, with Sharpe Ratios in out-of-sample tests above 0.7.

Financial markets perform two major functions. The first is the provision of liquidity in order to facilitate direct investment, hedging and diversification; the second is to ensure the efficient price discovery required in order to direct resources to where they can be best utilised within an economy. How well financial markets perform these functions is critical to the financial welfare of every individual in modern economies. As an example, retirement savings across the world are mostly invested in capital markets. Hence, the functioning of financial markets is linked to the standard of living of individuals. Technological advancements and new market regulations have in recent times significantly impacted how financial markets function, with no period in history having witnessed a more rapid pace of change than the last decade. Financial markets have become very complex, with most of the order execution now done by computer algorithms. New high-tech trading venues, such as dark pools, also now play outsized roles in financial markets. A lot of the impacts of these developments are poorly understood. In the EU particularly, the introduction of the Markets in Financial Instruments Directive (MiFID) and advancements in technology have combined to unleash a dramatic transformation of European capital markets. In order to better understand the role of high-tech trading venues in the modern financial markets' trading environment generally and in the UK in particular, I conduct three studies investigating questions linked to the three major developments in financial markets over the past decade; these are algorithmic/high-frequency trading, market fragmentation and dark trading. In the first study, I examine the changing relationship between the price impact of block trades and informed trading, by considering this phenomenon within a high-frequency trading environment on intraday and inter-day bases. I find that the price impact of block trades is stronger during the first hour of trading; this is consistent with the hypothesis that information accumulates overnight during non-trading hours. Furthermore, private information is gradually incorporated into prices despite heightened trading frequency. Evidence suggests that informed traders exploit superior information across trading days, and stocks with lower transparency exhibit stronger information diffusion effects when traded in blocks, thus informed block trading facilitates price discovery. The second study exploits the regulatory differences between the US and the EU to examine the impact of market fragmentation on dimensions of market quality. Unlike the US's Regulation National Market System, the EU's MiFID does not impose a formal exchange trading linkage or guarantee a best execution price. This has raised concerns about consolidated market quality in increasingly fragmented European markets. The second study therefore investigates the impact of visible trading fragmentation on the quality of the London equity market and find a quadratic relationship between fragmentation and adverse selection costs. At low levels of fragmentation, order flow competition reduces adverse selection costs, improves market transparency and enhances market efficiency by reducing arbitrage opportunities. However, high levels of fragmentation increase adverse selection costs. The final study compares the impact of lit and dark venues' liquidity on market liquidity. I find that compared with lit venues, dark venues proportionally contribute more liquidity to the aggregate market. This is because dark pools facilitate trades that otherwise might not easily have occurred in lit venues when the spread widens and the limit order queue builds up. I also find that informed and algorithmic trading hinder liquidity creation in lit and dark venues, while evidence also suggests that stocks exhibiting low levels of informed trading across the aggregate market drive dark venues' liquidity contribution.

Les travaux de la présente thèse portent sur l’estimation d'erreur a posteriori pour les solutions numériques par éléments finis de l'équation des ondes élastiques dans les milieux hétérogènes. Deux types d’estimation ont été développés. Le premier considère directement l’équation élastodynamique et conduit à un nouvel estimateur d'erreur a posteriori explicite en norme L∞ en temps. Les principales caractéristiques de cet estimateur explicite sont l'utilisation de la méthode de résidus et le développement de reconstructions en temps et en espace selon les différentes régularités exigées par les différents termes contribuant à l’obtention d’une borne supérieure. L’analyse numérique de cet estimateur dans le cas des maillages uniformes montre qu’il assure bien une borne supérieure mais avec une propriété asymptotique qui reste à améliorer. Le deuxième type d’estimateur d’erreur est développé dans le contexte de la propagation des ondes à haute fréquence dans des milieux hétérogènes à l’échelle mésoscopique. Il s’agit d’une nouvelle erreur en résidus basée sur l'équation de transfert radiatif, qui est obtenue par un développement asymptotique multi-échelle de l'équation d'onde en utilisant la transformation de Wigner en espace-temps. Les résidus sont exprimés en termes de densités énergétiques calculés dans l’espace des phases pour les solutions d’onde numériques transitoires par éléments finis. L’analyse numérique de cette erreur appliquée aux milieux homogènes et hétérogènes en 1D a permis de valider notre approche. Les champs d’application visés sont la propagation des ondes sismiques dans les milieux géophysiques ou la propagation des ondes ultrasonores dans les milieux polycristallins. / This thesis work deals with a posteriori error estimates for finite element solutions of the elastic wave equation in heterogeneous media. Two different a posteriori estimation approaches are developed. The first one, in a classical way, considers directly the elastodynamic equation and results in a new explicit error estimator in a non-natural L∞ norm in time. Its key features are the use of the residual method and the development of space and time reconstructions with respect to regularities required by different residual operators contributing to the proposed error bound. Numerical applications of the error bound with different mesh sizes show that it gives rise to a fully computable upper bound. However, its effectivity index and its asymptotic accuracy remain to be improved. The second error estimator is derived for high frequency wave propagation problem in heterogeneous media in the weak coupling regime. It is a new residual-type error based on the radiative transfer equation, which is derived by a multi-scale asymptotic expansion of the wave equation in terms of the spatio-temporal Wigner transforms of wave fields. The residual errors are in terms of angularly resolved energy quantities of numerical solutions of waves by finite element method. Numerical calculations of the defined errors in 1D homogeneous and heterogeneous media allow validating the proposed error estimation approach. The application field of this work is the numerical modelling of the seismic wave propagation in geophysical media or the ultrasonic wave propagation in polycrystalline materials.

Neste trabalho, apresentamos um conjunto de fatos empíricos e propriedades estatística de negociações em alta frequência, e discutimos algumas questões gerais comuns a dados de alta frequência tais: como discretização, espaçamento temporal irregular, durações correlacionadas, periodicidade diária, correlações temporais e as propriedades estatísticas dos fluxos de ordens. Logo apresentamos dois modelos da literatura,estilizados para a dinâmica do limit order book. No primeiro modelo os fluxo de ordens é descrito por processos de Poisson independentes, propomos para ele uma forma alternativa da prova de ergodicidade basejada em funções de Lyapunov. O segundo modelo é um modelo reduzido que toma em consideração dinâmicas tipo difusão para os tamanhos do bid e ask, e se foca só nas ordens como melhores preços, e modela explicitamente as cotações do bid e ask na presença de liquidez oculta. E por ultimo, propomos um modelo alternativo para a dinâmica do preço e do spread no limit order book, estudamos o comportamento assintótico do modelo e estabelecemos condições de ergodicidade e transitoridade. Além disso, consideramos a uma família de cadeias de Markov definidos nas sequências de caracteres (strings, ou palavras) com infinito alfabeto e para alguns exemplos inspirados nos modelos de negociações em alta frequência, obtemos condições para ergodicidade, transitoriedade e recorrência nula, para a qual usamos as técnicas de construção de funções Lyapunov. / In this work, we present a set of empirical facts and statistical properties of negotiations at high frequency and discuss some general issues common to high-frequency data such: as discretization, irregular spacing, correlated durations, daily periodicity, temporal correlations and the statistical properties of flows orders. Soon we present two models stylized in the literature for the dynamic limit order book. In the first model the order flow described by separate Poisson processes and we propose it to an alternative form of test ergodicity based on Lyapunov function. The second model is a reduced model that takes into consideration diffusion-type dynamics for the sizes of the bid and ask, and focus only on orders as best price and model explicitly quotes the bid and ask in the presence of hidden liquidity. And finally, we propose an alternative model for the price dynamics and spread in the limit order book, we study the asymptotic behavior of the model and established conditions of ergodicity. Furthermore, we consider the a family of Markov chains defined on the sequences of characters (strings, or words) with infinite alphabet. For some examples inspired by the models of high frequency trading we obtain a conditions for ergodicity, transience and null-recurrence. In order to prove this we use the construction of Lyapunov functions techniques.

Cette thèse est composée de trois chapitres distincts.Dans le premier chapitre, je montre que les mesures de liquidités traditionnelles, telles que la profondeur du marché, ne sont pas toujours pertinentes pour mesurer le bien-être des investisseurs. Je construis un modèle de marché conduit par les ordres et montre qu'une offre de liquidité élevée peut correspondre à de mauvaises conditions d'éxécution pour les fournisseurs de liquidité et à un bien-être relativement faible.Dans le deuxième chapitre, je modélise la vitesse des ajustements de prix à l'arrivée de nouvelles dans les marchés conduits pas les ordres, lorsque les investisseurs ont une capacité d'attention limitée.En raison de leur attention limitée, les investisseurs suivent imparfaitement l'arrivée de nouvelles. Ainsi, les prix s'ajustent aux nouvelles après un certain délai. Ce délai diminue lorsque le niveau d'attention des investisseurs augmente.Le délai d'ajustement des prix diminue également lorsque la fréquence à laquelle les nouvelles arrivent, augmente. Le troisième chapitre présente un travail écrit en collaboration avec Thierry Foucault. Nous construisons un modèle pour expliquer en quoi le trading à haute fréquence peut générer des "mini flash crashes" (un brusque changement de prix suivi d'un retour très rapide au niveau antérieur). Notre théorie est basée sur l'idée qu'il existe une tension entre la vitesse à laquelle l'information peut être acquise et la précision de cette information. Lorsque les traders à haute fréquence mettent en oeuvre des stratégies impliquant des réactions rapides à des événements de marché, ils augmentent leur risque à réagir à du bruit et génèrent ainsi des "mini flash crashes". Néanmoins, ils augmentent l'efficience informationnelle du marché. / This dissertation is made of three distinct chapters. In the first chapter, I show that traditional liquidity measures, such as market depth, are not always relevant to measure investors' welfare. I build a limit order market model and show that a high level of liquidity supply can correspond to poor execution conditions for liquidity providers and to a relatively low welfare.In the second chapter, I model the speed of price adjustments to news arrival in limit order markets when investors have limited attention.Because of limited attention, investors imperfectly monitor news arrival. Consequently prices reflect news with delay. This delay shrinks when investors' attention capacity increases. The price adjustment delay also decreases when the frequency of new arrival increases. The third chapter presents a joint work with Thierry Foucault. We build a model to explain why high frequency trading can generate mini-flash crashes (a sudden sharp change in the price of a stock followed by a very quick rversal). Our theory is based on the idea that there is a trade-off between speed and precision in the acquisition of information. When high frequency traders implement strategies involving fast reaction to market events, they increase their risk to trade on noise and thus generate mini flash crashes. Nonetheless they increase market efficiency.

FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico / O estudo para o desenvolvimento de uma fonte ininterrupta de energia com possibilidade de uso em sistema fotovoltaico, tem como motivaÃÃo que a larga escala da produÃÃo desse tipo de equipamento possa reduzir o custo dos conversores de eletrÃnica de potÃncia associados a uma instalaÃÃo fotovoltaica. O projeto proporem a uniÃo de topologias de conversores, resultando em uma UPS do tipo on-line com tensÃo de entrada e de saÃda de 220 Volts 60 Hz, potÃncia total de 715VA, rendimento de 88%, isolada em alta freqÃÃncia e com correÃÃo do fator de potÃncia na entrada. Sendo composta por um retificador na entrada com topologia de um conversor em ponte completa alimentado em corrente, esse conversor à responsÃvel por prover a correÃÃo do fator de potÃncia na entrada e da isolaÃÃo galvÃnica em alta freqÃÃncia. Um inversor em ponte completa com filtro LC e modulaÃÃo PWM unipolar, que à capaz de entregar uma tensÃo senoidal para a carga e um conversor boost de alto ganho que cumpre o papel de elevar a tensÃo de 24 Volts do banco de baterias para a tensÃo de 400 Volts do barramento de entrada do inversor. Cada conversor tem seu estudo teÃrico desenvolvido e ao final apÃs as especificaÃÃes e dimensionamentos sÃo mostrados os resultados experimentais do protÃtipo do projeto. Quando o sistema for aproveitado em uma instalaÃÃo fotovoltaica somente o inversor e o conversor boost de alto ganho sÃo utilizados. / The study of the development of initerruptible power supply to be used in a photovoltaic system has as motivation that the wide UPS production scale can reduce the cost of power electronics converters associated with a photovoltaic system. The project proposes a topology of an on-line UPS, with 220 Volts, 60 Hz input/output voltage, 715 VA power, 88% efficiency, High frequency isolation and Power factor correction. The Project consists on a rectifier, it is responsible for providing the input power factor correction and the high frequency isolation. An inverter, it supply the load with a output sinusoidal voltage and a high gain boost converter that increase the voltage from the battery pack up to the inverter. When the project is used in a photovoltaic system, it is only used the inverter and the high gain boost converter.

Introdução: A Síndrome do Desconforto Respiratório Agudo (SDRA) apresenta alta incidência e mortalidade em pacientes de terapia intensiva. A ventilação mecânica é o principal suporte para os pacientes que apresentam-se com SDRA, entretanto ainda existe muito debate sobre a melhor estratégia ventilatória a ser adotada, pois a ventilação mecânica pode ser lesiva aos pulmões e aumentar a mortalidade se mal ajustada. Um dos principais mecanismos de lesão pulmonar induzida pela ventilação é o uso de volumes correntes altos, havendo evidência na literatura que a utilização de volumes correntes menores fornece uma ventilação dita protetora, a qual aumenta a probabilidade de sobrevivência. Objetivo: Explorar se uma estratégia ventilatória de alta frequência com pressão positiva (HFPPV) realizada através de um ventilador mecânico convencional (Servo-300) é capaz de permitir uma maior redução do volume corrente e estabilização da PaCO2 em um modelo de SDRA severa, inicialmente ventilado com uma estratégia protetora. Métodos: Estudo prospectivo, experimental que utilizou oito porcos que foram submetidos a uma lesão pulmonar através de lavagem pulmonar com soro fisiológico e ventilação mecânica lesiva. Em seguida, os animais foram ventilados com um volume corrente de 6 mL/kg, seguido de uma randomização de sequências diferentes de frequências respiratórias (30, 60, 60 com pausa inspiratória de 10 e 30%, 90, 120, 150, 60 com manobra de recrutamento alveolar mais titulação da PEEP e HFOV com 5 Hertz), até obter estabilização da PaCO2 entre 57 63 mmHg por 30 minutos. O ventilador Servo-300 foi utilizado para HFPPV e o ventilador SensorMedics 3100B utilizado para fornecer a ventilação oscilatória de alta frequência (HFOV). Dados são apresentados como mediana [P25th,P75th]. Principais Resultados: O peso dos animais foi de 34 [29,36] kg. Após a lesão pulmonar, a relação P/F, o shunt pulmonar e a complacência estática dos animais ficaram em 92 [63,118] mmHg, 26 [17,31] % e 11 [8,14] mL/cmH2O respectivamente. O PEEP total usado foi de 14 [10,17] cmH2O durante o experimento. Da frequência respiratória de 35 (e com volume corrente de 6 mL/kg) até a frequência ventilatória de 150 rpm, a PaCO2 foi 81 [78,92] mmHg para 60 [58,63] mmHg (P=0.001), o volume corrente (VT) progressivamente caiu de 6.1 [5.9,6.2] para 3.8 [3.7,4.2] mL/kg (P<0.001), a pressão de platô de 29 [26,30] para 27 [25,29] cmH2O (P=0.306) respectivamente. Não houve nenhum comprometimento hemodinâmico ou da oxigenação, enquanto os animais utilizaram a FiO2 = 1. Conclusões: Utilizando-se de uma ventilação mecânica protetora, a estratégia de HFPPV realizada com um ventilador mecânico convencional em um modelo animal de SDRA severa permitiu maior redução do volume corrente, bem como da pressão de platô. Esta estratégia também permitiu a manutenção de PaCO2 em níveis clinicamente aceitáveis / Introduction: Acute respiratory distress syndrome (ARDS) has a high incidence and mortality between critical ill patients. The mechanical ventilation is the most important support for these patients with ARDS. However, until now there is an important debate about how is the best ventilatory strategy to use, because the mechanical ventilation if not well set can cause lung injury and increase mortality. The use of high tidal volume is one of the most important mechanics of ventilation induced lung injury and there is evidence in the literature that using low tidal volume is a protective ventilation with better survival. Objective: To explore if high frequency positive pressure ventilation (HFPPV) delivered by a conventional ventilator (Servo-300) is able to allow further tidal volume reductions and to stabilize PaCO2 in a severe acute respiratory distress syndrome (ARDS) model initially ventilated with a protective ventilation. Methods: A prospective and experimental laboratory study where eight Agroceres pigs were instrumented and followed by induction of acute lung injury with sequential pulmonary lavages and injurious ventilation. Afterwards, the animals were ventilated with a tidal volume of 6 mL/kg, followed by a randomized sequence of respiratory rates (30, 60, 60 with pauses of 10 and 30% of the inspiratory time, 90, 120, 150, 60 with alveolar recruitment maneuver and PEEP titration and 5 Hertz of HFOV), until PaCO2 stabilization between 57 63 mmHg for 30 minutes. The Servo-300 ventilator was used for HFPPV and the ventilator SensorMedics 3100B was used for HFOV. Data are shown as median (P25th,P75th). Measurements and Main Results: Animals weight was 34 [29,36] kg. After lung injury, the P/F ratio, pulmonary shunt and static compliance of animals were 92 [63,118] mmHg, 26 [17,31] % and 11 [8,14] mL/cmH2O respectively. The total PEEP used was 14 [10,17] cmH2O throughout the experiment. From the respiratory rates of 35 (while ventilating with 6 mL/kg) to 150 breaths/ minute, the PaCO2 was 81 [78,92] mmHg and 60 [58,63] mmHg (P=0.001), the tidal volume progressively felt from 6.1 [5.9,6.2] to 3.8 [3.7,4.2] mL/kg (P<0.001), the plateau pressure was 29 [26,30] and 27[25,29] cmH2O (P=0.306) respectively. There were no detrimental effects in the hemodynamics and blood oxygenation, while the animals were using a FiO2 = 1. Conclusions: During protective mechanical ventilation, HFPPV delivered by a conventional ventilator in a severe ARDS swine model allows further tidal volume reductions. This strategy also allowed the maintenance of PaCO2 in clinically acceptable levels

L’excès de synchronisation dans le réseau cortico-sous-cortical est une caractéristique majeure de la maladie de Parkinson. La stimulation cérébrale profonde (DBS) à haute fréquence (HF) des ganglions de la base modifie ces synchronies et améliore significativement les troubles moteurs. Il n’était pas encore connu si l’excès de synchronisation dans le cortex moteur primaire (M1) est présent avant les signes moteurs et si la modulation antidromique des réseaux corticaux via la stimulation HF de la voie hyperdirecte cortico-subthalamique suffit à le désynchroniser. Nous avons étudié la synchronisation des activités spontanées dans M1 de souris juvéniles PINK1 -/-, modèle génétique de Parkinson (PARK6) par imagerie calcique bi-photonique in vitro et l’avons comparée à celle de souris contrôle (P14-P16). Nous avons testé l’impact de la stimulation HF des fibres cortico-subthalamiques (région subthalamique) sur ces synchronies corticales. A un stade précoce, les réseaux M1 présentent un excès de synchronisation et, dans notre modèle de tranche, la DBS HF normalise le patron de synchronisation, plaidant pour un rôle primordial de la modulation antidromique de l’activité corticale via la voie hyperdirecte. En conclusion, nous proposons, grâce à ce modèle génétique progressif, que (1) des activités de réseau pathologiques sont présentes dans M1 bien avant les premiers signes moteurs et (2) que la modulation par voie antidromique de ces réseaux corticaux est un mécanisme essentiel d’action de la DBS HF. Ces résultats montrent qu’une pathologie dégénérative est détectable très tôt dans le développement (neuroarchéologie) mais ne s’exprimer somatiquement que tardivement. / The excess of synchronization of neuronal activities within the cortico-basal ganglia network is a hallmark of the pathophysiology of Parkinson’s disease. High frequency deep brain stimulation (DBS) applied to various basal ganglia nuclei dampens the synchronized activity in the whole network, and brings about a significant motor improvement. However it is not to date established whether an early presymptomatic abnormal pattern of synchronization is present in the primary motor cortex long before motor signs, nor whether its antidromic modulation via the hyperdirect cortico-subthalamic pathway is sufficient to remove its excess of synchronization. To answer these questions we studied the synchronization of spontaneous activities in the primary motor cortex of PINK-/- mice (genetic rodent model of Parkinson’s (PARK6), a progressive model) and compared it with age-matched control mice (P14-16 (wild-type)) by means of two-photon calcium imaging. Secondly, we analyzed in vitro the impact of the high frequency stimulation of cortico-subthalamic fibers on the pattern of synchronization of cortical networks. We show that, (1) at an early stage of development, there is an excess of synchronized activity in primary motor cortical networks and that, (2) antidromic modulation of cortical activity is a key mechanism to account for the normalization of hyper synchronized activity. These results show that a neurodegenerative adult pathology may begin early during development (neuroarcheology) though clinical signs appear late in adulthood. Moreover, antidromic invasion of a network seems to be a key mechanism of deep brain stimulation.

A presença de antibióticos no meio ambiente aquático tem causado crescente preocupação mundial. Além dos relatos de resistência de bactérias a antibióticos, essa classe de fármacos também pode causar efeitos tóxicos e atuar como perturbadores endócrinos em diversos organismos vivos e, possivelmente, em humanos. Dentre os antibióticos comumente usados destacam-se as sulfonamidas, detectadas em águas subterrâneas e superficiais. Os processos avançados de oxidação (POA) têm sido apontados como tecnologias eficientes para tratamento de poluentes recalcitrantes em diferentes matrizes aquosas. Dentre os POA, o processo foto-Fenton é uma alternativa para a degradação de compostos não biodegradáveis, incluindo fármacos. Uma vez que a principal limitação do processo é o intervalo de pH (2,5- 4,0), a reação pode ser vantajosamente conduzida empregando-se substâncias bio-orgânicas solúveis (BOS) como agentes complexantes de Fe3+ em condições ligeiramente ácidas (pH 5). Por sua vez, o emprego da energia ultrassônica tem sido menos estudado. Nesse contexto, o objetivo deste trabalho é estudar a degradação do antibiótico sulfadiazina (SDZ) por meio do processo foto-Fenton na presença de substâncias bio-orgânicas solúveis (UVvis/ Fe3+/H2O2/BOS) e do processo de cavitação por meio de ultrassom (US). Os resultados obtidos mostram que a sulfadiazina é eficientemente degradada por ultrassom de alta frequência. As maiores porcentagens e taxas de remoção são obtidas usando menor frequência de operação (580 kHz), maior potência dissipada e em pH ligeiramente ácido (melhor condição: pH 5,5). Além disso, a reação de Fenton, combinada com o tratamento US, melhorou notavelmente a degradação da SDZ, particularmente quando quantidades extras de H2O2 foram adicionadas ao sistema. Por sua vez, o uso de BOS como aditivos no processo foto-Fenton apresenta influência marcante na fotodegradação da SDZ em condições ligeiramente ácidas (pH 5). Os BOS podem estabilizar espécies de ferro em solução aquosa em pH próximos ao neutro, o que constitui uma propriedade de grande interesse. Sob as condições estudadas, o BOS CVT230 foi mais eficiente do que FORSUD, provavelmente devido às diferenças nos grupos funcionais presentes na composição destas substâncias. Finalmente, foram calculados os indicadores de consumo de energia elétrica por ordem de grandeza (EEO) para o processo de ultrassom (1572 kW h m-3 ordem-1) e área do coletor por ordem de grandeza (ACO) para o processo foto-Fenton (8,07 m2 m-3 ordem-1). / The potential impacts of antibiotic residues in the environment have become an emerging concern during recent years due to their relation with the development of resistant bacteria, and in some cases to their ability to cause toxic and endocrine disrupting effects in humans and other living organisms. Highlighted among the commonly used antibiotics are the sulfonamides, detected in groundwater and surface water. Advanced oxidation processes (AOP) might constitute an important alternative to deal with pharmaceuticals degradation. Among them, the photo-Fenton process has been widely used. One of its major drawbacks is the highly acidic pH needed (2,5-4,0) to avoid the formation of photochemically inactive iron oxides and hydroxides. The ability of soluble bio-organic substances (SBO) to complex metal cations such as iron is useful for the development of photo-Fenton at mild acidic conditions (pH 5). In turn, the use of ultrasonic energy has been less studied. In this context, the aim of this work is to study the degradation of the antibiotic sulfadiazine (SDZ) by the photo-Fenton process in the presence of soluble bio-organic substances (UV-vis/Fe3+/H2O2/SBO) and by ultrasonic cavitation (US). The results confirm that SDZ is effectively degraded by highfrequency ultrasound. Higher SDZ percent removals and removal rates were observed for the lowest operating frequency (580 kHz), higher dissipated power, and in slightly acidic solution (pH 5.5). On the other hand, SDZ degradation is highly improved in the case of the US/ Fe(II)/H2O2 system. The use of the SBO as Fenton additives in turn has a remarkable influence in SDZ photodegradation at slightly acid conditions (pH 5). This could be ascertained to the complexation of iron by the SBO, hence maintained in the reaction medium as a photoactive species. Under the studied conditions, the BOS CVT230 was more efficient than FORSUD, probably due to differences in the functional groups present in the composition of these substances. Finally, the figures-of merit electrical energy per order (EEO) and collector area per order (ACO) were calculated for the ultrasound (1572 kW h m-3 ordem-1) and photo-Fenton (8,07 m2 m-3 ordem-1) processes respectively.