Alcohol abuse disorders (AUD) represent a serious worldwide health problem with far reaching social, financial, and interpersonal implications. One of the most devastating facets of these disorders is the propensity to relapse following periods of abstinence. Ethanol withdrawal (EWD) is believed to promote relapse by increasing anxiety and craving, and may contribute to the development of cognitive decline associated with long-term dependence. Clinical data suggest that stress also plays a main role in both the development of AUD as well as relapse to drinking. As a physiological stressor, EtOH elevates levels of stress hormones (cortisol in humans, corticosterone (CORT) in the rat). Both CORT and EtOH have been shown to alter the composition, function, and activity of the N-methyl-D-aspartate (NMDA) receptor, and in particular, the NR2B subunit of this receptor. These alterations have been suggested to mediate EWD, which may negatively impact abstinence rates. This synergistic interaction between EtOH and CORT may present a therapeutic target for the treatment of EWD. In fact, data suggest that blocking the glucocorticoid receptor, which is a main target for CORT, with RU-486 could promote abstinence, as treatment with the drug has been shown to reduce consumption and the development dependence, as well as the severity of EWD and the cognitive deficits following EWD. However, these latter effects have not been validated in models of voluntary EtOH consumption. As there is considerable evidence that active versus passive intake can significantly impact neuroadaptations to ethanol this is an important consideration. These studies sought to characterize consumption and evaluate the development of dependence in a chronic voluntary model of intermittent access (IA) to EtOH. CORT plasma levels and protein expression of the glucocorticoid and NR2B receptors were measured during and/or following exposure. Finally, to assess the role of CORT in EtOH consumption and the development of dependence, the glucocorticoid receptor antagonist ORG-34517 was administered during access to EtOH. IA access to 20% EtOH produced varying levels of consumption (2.0-6.7g/kg/24hr exposure) and blood EtOH levels (6.3-116.9 mg/dl), but did not significantly affect food consumption or weight gain. Baseline CORT levels were found to be predictive of subsequent EtOH consumption and levels of consumption were sufficient to elevate CORT levels following one hour of EtOH exposure. Further, IA to EtOH was sufficient to produce dependence, as measured by elevations in the acoustic startle reflex following 26 hours and five days of withdrawal. No alteration in protein expression was observed regarding either the NR2B or glucocorticoid receptors and exposure to ORG-34517 had no effect on consumption or withdrawal.

Excessive and compulsive ethanol drinking is one of the most serious public health issues. Therefore, it is vital to increase the knowledge about risks and protection for alcohol use disorders (AUD) to optimize prevention and treatment strategies. Ethanol consumption commonly initiates during adolescence when extensive neuronal maturation and development also occurs. Early exposure to ethanol is a risk factor for AUD, but the effects of adolescent drinking and the basis for the individual susceptibility to AUD are not fully understood. The interactions between genotype and environmental factors determine the individual risk for AUD and this thesis aimed to examine the environmental impact. The specific aims were to investigate 1) how early-life conditions affect adolescent voluntary ethanol drinking, behavioural profiles, endogenous opioids and response to treatment with an opioid antagonist (naltrexone), and 2) whether alterations detected in the offspring may be mediated by variations in maternal behaviour. A rodent maternal separation (MS) model was used to mimic a protective and risk-inducing early-life environment, respectively, with the use of 15 min (MS15) or 360 min (MS360) of daily MS. The main findings were 1) the MS360, but not the MS15 rats, responded to naltrexone following adolescent ethanol drinking; all adolescent rats had a high voluntary ethanol intake independent of early environmental conditions whereas in the adult groups the MS360, but not the MS15 rats, increased their ethanol intake and preference over time; adolescent ethanol exposure resulted in higher dynorphin levels in hippocampus and higher Met-enkephalin-Arg6Phe7 in the amygdala, independently of rearing conditions, 2) behavioural profiling using the multivariate concentric square field™ test showed: the young MS360 rats had increased risk assessment and risk taking behaviour compared to the young MS15 rats; the young MS15 rats increased, whereas the young MS360 rats decreased, their risk assessment and risk taking behaviour over time; differences in pup-retrieval strategies where the MS360 dams retrieved some pups into a safe area but as compared to MS15 rats they left more pups in a risk area; increased risk assessment behaviour in the MS360 dams immediately after weaning. Taken together, early-life environmental conditions alter adult but not adolescent drinking, the response to naltrexone, and behaviour in dams and offspring. Adolescent rats consumed more ethanol independent of rearing conditions and displayed increased opioid levels in brain areas related to cognition and addiction.

Patients with Peripheral Arterial Disease have a reduced capacity for exercise, the exact causes of which are poorly understood. This thesis investigated alternative testing procedures that aim to provide a more complete and precise description of the exercise capacities of these patients. Furthermore, the potential roles of gastrocnemius muscle fibre morphometry, capillary supply and glycogen stores in the exercise tolerance of PAD patients were studied. Study one aimed to determine the effect of test repetition on maximal exercise performance and test-to-test variability in PAD patients using an incremental treadmill walking test (T) (n=5), an incremental cycle test (C) (n=5), and incremental endurance (PF-endurance) and maximal strength (PF-strength) plantar flexion tests (n=5). Tests were conducted once per week for eight weeks. Performance was stable on the T (~530 s) and C (~500 s) tests across the eight weeks. Test-to-test variance on T decreased from 16%CV (CV: coefficient of variation) to 6%CV (p=.21,NS), and from ~8%CV to 2%CV on C (p<.05) over the eight week period. Variance of peak gas exchange variables tended to decrease with performance variance on both tests; however, other physiological variables, and the associated variance levels, were stable throughout the study. PF strength (635-712N) gradually increased over the initial 2-3 weeks (p<.05) which was accompanied by a reduction in variance from ~8%CV to ~3%CV (p<.05). Similarly, PF endurance increased over the first two weeks (~32,000 to 41500 N.s-1) while variance of this measure fell from ~21%CV to ~10%CV (p<.05) over the study duration. It is concluded that the implementation of familiarisation sessions leads to a reduction in whole body and local calf muscular performance variance in patients with PAD. Using a randomised crossover design, study two aimed to compare performance and the physiological and symptomatic responses between a T test and a C test in 16 patients with PAD. Peak exercise time on C (690 s) was greater than that on T (495 s); however the two were significantly correlated (n=16, r=.69, p<.05). Peak HR (120 bpm), VO2 (~1.22 l.min-1) and rate pressure product (~20') did not differ between the two tests, nor did the post exercise ankle pressure (T: 56; C: 61 mmHg). In two subjects with lower back pain during C, the ankle pressure of their "worst" limbs failed to fall by >10mmHg. Performance on both the T and C tests was closely related to the onset of leg symptoms; however the site of pain during C was much more variable than during T. Incremental cycle testing would overcome some of the limitations of treadmill testing (e.g. measurement of mechanical work), and it appears to be an acceptable alternative for measuring the exercise capacity and physiological exercise responses in known claudicants. Use of cycle ergometry for the diagnosis of PAD requires testing in the general population. Study three aimed to compare whole body (T test and C test) and local calf muscular (PF strength and endurance) exercise performance between 16 PAD patients (age: 63 ± 2; BMI: 25.9 ± 1.1) and 13 healthy, sedentary control (CON) subjects (age: 62 ± 1; BMI: 25.9 ± 0.4), and to describe relationships between the whole body and local calf muscular exercise capacities within the two groups. Furthermore, this study aimed to compare several histochemical characteristics of the medial gastrocnemius muscle fibres between PAD and CON, and to establish whether these factors were related to the exercise capacities of both groups. Maximal performance on T was 59% lower in the PAD group compared with the CON group, as was performance on C (50%), PF strength (25%), and PF endurance (58%). Compared with CON, PAD patients had a lower estimated calf muscle mass and a slight reduction (10%) in muscle fibre size (p=.14, NS). They also had a lower proportion of type I fibres (PAD: 49%; CON: 62%) that was offset by a greater proportion of type IIA fibres (PAD: 27%; CON: 16%), and a reduction in the capillary contacts per muscle fibre (PAD: 1.63; CON: 2.12) compared with CON. When expressed relative to fibre area there were no differences in capillarisation between PAD and CON; however this index was significantly related to resting and post exercise ABI in the PAD patients. There were no differences in the mixed muscle [glycogen], nor the optical density of glycogen in the individual fibres, between the two groups. PF endurance was poorly predictive of walking performance, and did not correlate with any of the morphological variables in both groups. Calf muscle mass correlated with PF strength (r=.59 - .62), and strength was correlated with T performance (r= .61 - .63) in both groups. In the PAD patients, T performance was correlated with the cross sectional area (n=12, r=.72, p<.05), capillary contacts (n=10, r=.81, p<.05) and glycogen density (n=9, r=.81, p<.05) of type I fibres. This study confirms that a reduction in calf strength, which appears to be mediated through muscle atrophy, plays some role in the reduced exercise capacity of claudicants. While both fibre area and capillary supply seem to be of relevance to the exercise capacity of PAD patients, these two factors are closely linked and further research is required to establish the determinants, and relative importance of both. An important, and possibly limiting role of carbohydrate oxidisation in PAD patients is supported by the strong relationship between type I glycogen stores and whole body exercise capacity.

In critically ill patients, the pathophysiology of sepsis can affect the interactions between the antibiotic, the bacteria and the patient, leading to potential therapeutic failure and the development of antibiotic resistance. It is well acknowledged that research that optimises antibiotic exposure will assist improvement of outcomes in this patient group. Although beta-lactam antibiotics, such as piperacillin and meropenem, are commonly selected for empiric therapy of sepsis, dosing is unlikely to be optimal. In patients without renal dysfunction, data suggests that disease-induced alterations to pharmacokinetic parameters result in low trough concentrations for significant periods within a dosing interval. Administration of these time-dependent antibiotics by continuous infusion has been suggested to improve the pharmacokinetic-pharmacodynamic profile. Knowledge of concentrations in the extracellular fluid of human tissue, which is the target site of most pathogens, is particularly instructive. Extracellular fluid concentrations can be determined using techniques such as microdialysis. Therefore, the principal aims of this Thesis were to determine the plasma and subcutaneous tissue pharmacokinetics of piperacillin and meropenem administered by bolus dosing and continuous infusion in critically ill patients with sepsis; and to use Monte Carlo simulations to compare the ability of different dosing strategies to achieve pharmacodynamic endpoints. This Thesis also sought to compare the clinical outcomes of bolus dosing and continuous infusion of a beta-lactam antibiotic, ceftriaxone, in a prospective randomised controlled trial and to perform a meta-analysis on clinical outcomes from other similar published studies. Finally, this Thesis aimed to systematically review the published literature to determine any correlation between antibiotic dosing and the development of antibiotic resistance. The results of the pharmacokinetic studies, using piperacillin and meropenem, indicate that beta-lactam distribution into subcutaneous tissue, in critically ill patients with sepsis, is less than that observed in previous studies in healthy volunteers yet superior to studies in patients with septic shock. This supports the notion that the peripheral concentration of drugs may be inversely related to the level of sickness severity. Administration by continuous infusion was found to maintain statistically significantly higher trough beta-lactam concentrations in both plasma and subcutaneous tissue. Further analysis of the plasma data using population pharmacokinetic modeling and Monte Carlo simulations described significant pharmacodynamic advantages for administering meropenem or piperacillin by continuous infusion to organisms with high minimum inhibitory concentrations. Given the documented pharmacodynamic advantages for administering beta-lactams by continuous infusion, a prospective randomized controlled clinical trial was conducted using the beta-lactam antibiotic ceftriaxone. In 57 critically ill patients, we found equivalence between continuous infusion and bolus dosing in the intention-to-treat analysis. However, our a priori analysis criteria, requiring patients receive at least 4-days antibiotic treatment, found significant clinical and bacteriological advantages for administration by continuous infusion. To further investigate any clinical differences between bolus dosing and continuous infusion of beta-lactam antibiotics, we performed a meta-analysis of all published studies. Our analysis of the 13 published prospective randomized controlled trials (846 hospitalised patients) showed equivalence of continuous infusion and bolus dosing. Possible confounders observed within, and between the studies, make interpretation of these results challenging. However, two large retrospective cohorts not included in the meta-analysis, found definitive clinical and bacteriological advantages suggesting further research may be appropriate. The possible relationship between antibiotic dosing, or exposures, on the development of resistance was investigated using a structured review of the published literature. Our analysis of relevant papers found a wealth of data describing increasing levels of resistance with sub-optimal antibiotic dosing, particularly for fluoroquinolone antibiotics, but also for other classes including beta-lactams. These results demonstrate the importance of optimizing antibiotic dosing to decrease the development of antibiotic susceptibility from sub-optimal dosing, particularly for critically ill patients who are likely to have low drug concentrations. The results of this Thesis, suggest that a large, prospective, multi-centre randomised controlled trial in critically ill patients with sepsis, is required to definitively determine the clinical utility of administration of beta-lactam antibiotics by continuous infusion.

Submitted by Claudia Rocha (claudia.rocha@udesc.br) on 2017-12-14T12:26:27Z No. of bitstreams: 1 PGEF17MA077.pdf: 4440058 bytes, checksum: 3e93f4228f2cb823f57ec2cc6afed76a (MD5) / Made available in DSpace on 2017-12-14T12:26:27Z (GMT). No. of bitstreams: 1 PGEF17MA077.pdf: 4440058 bytes, checksum: 3e93f4228f2cb823f57ec2cc6afed76a (MD5) Previous issue date: 2017-02-24 / Capes / The addition of water-repelling polymers as soil-borers aims to increase soil water retention capacity, providing better quality of seedlings, not making them dependent on climatic conditions throughout the year. In this way, the objective of the present work was to evaluate the effect of hydrogel use in the planting of Eucalyptus sp. In pots, related to different water management, seeking to provide information on the efficiency of hydrogel use simulating field conditions. The work was separated into four species (Eucalyptus urograndis of clonal origin, Eucalyptus urograndis of seminal origin, Eucalyptus dunnii and Eucalyptus benthamii). The experiment was conducted in the municipality of Lages - SC, in the forest nursery of the CAV / UDESC, conducted in a DIC, factorial scheme, where the levels of factor "A" referred to the absence and presence of hydrogel and levels of factor " B "to water management (Irrigation only at planting, 8 days, 4 days and daily). After planting until the end of the experimental period, the evaluation of the symptoms of water stress, morphological characteristics, chlorophyll content, soil water content and gas exchange were performed. Statistical differences were assessed by analysis of variance followed by the Scott-Knott or Tukey test.) At the end of the experiment, the development of the seedlings was evaluated through the increase in diameter and height, dry biomass. The determination of the available water retention curve was also performed. As a result, the use of the hydrogel provided a significant increase in water retention in the soil, consequently a delay in the symptoms of water stress, increasing the rate of survival over time. Deficit water, in the absence of the hydrogel, resulted in reductions in height, diameter, leaf area, dry biomass and chlorophyll indexes, being a limiting factor for stomatal opening, contributing to the decrease in carbon assimilation by photosynthesis. The lower the water availability, the lower the values of A, gs and E, and the WUE increased when the water availability decreased. In general, the results obtained in relation to the use of hydro-ether polymers confirm the information that the addition of hydrogels in the soil optimizes the water availability and can reduce the mortality problems in the planting / A adição de polímeros hidroretentores como condicionadores de solo visam aumentar a capacidade de retenção de água no solo, propiciando melhor qualidade das mudas, não as tornando dependentes das condições climáticas ao longo do ano. Desta forma, o objetivo do presente trabalho foi avaliar o efeito do uso do hidrogel no plantio de mudas de Eucalyptus sp. em vasos, relacionados com diferentes manejos hídricos, buscando fornecer informações sobre a eficiência do uso do hidrogel simulando condições de campo. O trabalho foi separado em quatro espécies (Eucalyptus urograndis de origem clonal, Eucalyptus urograndis de origem seminal, Eucalyptus dunnii e Eucalyptus benthamii). O experimento foi conduzido no município de Lages – SC, no viveiro florestal do CAV/ UDESC, realizado em DIC, esquema fatorial, onde os níveis do fator “A” referiram-se a ausência e a presença de hidrogel e os níveis do fator “B” ao manejo hídrico (irrigação somente no plantio, 8 dias, 4 dias e diariamente). Depois do plantio até o fim do período experimental foram realizadas avaliações da sintomatologia do estresse hídrico, características morfológicas, teores de clorofila, teor de água no solo e trocas gasosas. As diferenças estatísticas foram avaliadas segundo análise de variância seguidas do teste de Scott-Knott ou Tukey. Ao final do experimento foi avaliado o desenvolvimento das mudas através do incremento em diâmetro e altura, biomassa seca. Também realizou-se a determinação da curva de retenção de água disponível. Como resultado, o uso do hidrogel proporcionou um aumento significativo na retenção de água no solo, consequentemente um atraso nos sintomas de estresse hídrico, aumentando a taxa de sobrevivência ao longo do tempo. O estresse hídrico, na ausência do hidrogel, resultou em reduções na altura, diâmetro, área foliar, biomassa seca e índices de clorofila, sendo um fator limitante para a abertura estomática, contribuindo para a queda na assimilação de carbono pela fotossíntese. Quanto menor a disponibilidade de água, menor os valores de A, gs e E, sendo que o WUE aumentou quando diminuiu a disponibilidade de água. Em geral, os resultados obtidos com relação ao uso de polímeros hidroretentores confirmam a informação que a adição de hidrogéis no solo otimiza a disponibilidade de água, podendo diminuir os problemas de mortalidade no plantio

Syfte och frågeställningar Syftet med studien var att undersöka effekten av cykelintervaller som komplement till handbollsträning för att förbättra prestationsförmågan hos manliga ungdomsspelare på elitnivå. Den frågeställning studien svarat på är om cykelintervaller som komplement till handbollsträning har några effekter på den specifika prestationsförmågan. Metod En kvantitativ experimentell studie genomfördes med 13 manliga ungdomsspelare (fp) i handboll. Under 3 veckor fick fp genomföra cykelintervaller som komplement till ordinarie träning 2 gånger i veckan. Effekten av träningen kontrollerades genom förtest och eftertest där fp:s aeroba förmåga (Yo-Yo IR L1), anaeroba kapacitet (150 m shuttle run) samt anaeroba effekt (CMJ) testades. Utifrån resultaten vid förtesterna delades fp in i antingen cykelgrupp (CG) eller kontrollgrupp (KG). Indelning gjordes genom matchning av fp:s profil följt av lottning. CG genomförde 2 olika intervalltyper, 4 min intervaller och 30 sekunders intervaller med ökat antal set över tid. Efter 3 veckor, totalt 6 träningspass, fick samtliga fp återigen genomföra tester med identiskt testförfarande. Genom detta kunde skillnader i utveckling av delkapaciteter relevanta för handboll mellan grupperna utvärderas. Resultat CG förbättrade signifikant både sitt Yo-Yo IR L1 resultat (p≤0,05) samt resultatet i de tre 150 m shuttle run mätningarna (löpning 1, p=0,03; löpning 2, p&lt;0,001; differens löpning 1 och 2, p&lt;0,001). KG hade ingen förbättring i Yo-Yo IR L1 och bara en signifikant trend till förbättring i löpning 2 i 150 m shuttle run (p=0,08). Mellan grupperna förelåg dock inte några signifikanta skillnader. Det sågs ingen förändring i någon av grupperna vid eftertesterna av CMJ.  Slutsats Trots att CG förbättrade sig signifikant i såväl aeroba som anaeroba tester förelåg ingen signifikant skillnad mellan grupperna vilket bland annat tros bero på för få fp samt för kort interventionstid. Resultatet indikerar dock att cykelträning kan vara av värde för handbollsspelare men vidare forskning på en större försöksgrupp och längre interventionstid behövs för att med säkerhet kunna dra några generella slutsatser gällande cykelträningens effektivitet för handbollsspelare.

Le syndrome d’apnées obstructives du sommeil (SAOS) affecte 5 à 20% de la population générale et est associée à des complications cardiovasculaires, ce qui en fait un véritable problème de santé publique. Les épisodes itératifs d’obstruction pharyngée nocturne qui le caractérisent aboutissent à une hypoxie intermittente, elle-même impliquée dans ces complications cardiovasculaires. A ce jour, les mécanismes reliant SAOS et athérosclérose restent méconnus. De plus, le traitement de référence du SAOS par pression positive continue présente dans certaines populations une efficacité limitée sur les conséquences cardiovasculaires du SAOS, d’où la nécessité de développer de nouvelles thérapeutiques ciblant spécifiquement le processus athéromateux. Des perturbations du métabolisme de l’acide arachidonique à l’origine de la synthèse d’eicosanoïdes pro-inflammatoires ont déjà été décrites au cours du SAOS et ont été associées au processus athéromateux. Le but de ce travail a donc été de préciser par une approche translationnelle le rôle de certains de ces eicosanoïdes, à savoir le thromboxane A2 et les cystéinyl-leucotriènes dans l’athérogénèse associée au SAOS et de les évaluer en tant que potentielles cibles thérapeutiques. Ces travaux ont montré non seulement une activation des voies métaboliques du thromboxane A2 et des cystéinyl-leucotriènes au cours du SAOS, mais également leur association avec le processus athéromateux. Enfin, des traitements pharmacologiques ciblant spécifiquement ces médiateurs étaient capables de ralentir la progression de l’athérosclérose en lien avec le SAOS dans un modèle murin de SAOS. Ces travaux démontrent donc le rôle du thromboxane A2 et des cystéinyl-leucotriènes dans l’athérosclérose associée au SAOS, et positionnent ces deux voies métaboliques comme des cibles thérapeutiques potentielles pour traiter les conséquences cardiovasculaires du SAOS. / Obstructive sleep apnea (OSA) is a really public health problem since it affects 5 to 20% of general population and is associated with increased cardiovascular morbidity and mortality. Repetitive nocturnal pharyngeal obstruction leads to intermittent hypoxia, which is responsible of premature atherosclerosis and also cardiovascular complications.Nevertheless, mechanims linking OSA and atherosclerosis remains poorly understood. In addition, continuous positive airway pressure (CPAP) application, which is the gold standard treatment of OSA, has poor effect on OSA cardiovascular consequences in some populations, highlighting the need of alternative therapeutic strategies. Alterations of several eicosanoids resulting to arachidonate metabolism had already been described during OSA, these latter being associated with vascular remodeling. The aim of this work was to precise trough a translational approach the contribution of some eicosanoids, especially thromboxane A2 and cysteinyl-leukotriene on OSA related-atherogenesis and also to evaluate these latter as therapeutic target.We had shown an activation of both thromboxane A2 and cysteinyl-leukotriene pathways in OSA, this latter being associated with vascular remodeling. In addition, pharmacological treatment by cyclooxygenase type 1 inhibitor or CysLT1 receptor antagonist reduced OSA-related atherosclerosis progression in an OSA mouse model.Finally, these works had demonstrated the implication of both thromboxane A2 and cysteinyl-leukotrienes activation in OSA-related atherosclerosis, but also the potential therapeutic of these targets to treat cardiovascular consequences of OSA.

[pt] A produção de petróleo offshore tem requerido cada vez mais a utilização de equipamentos de bombeio no leito marinho para a produção de poços a longas distâncias das unidades de produção. A grande maioria destes equipamentos tem dificuldade de operar com a presença de gás, ainda mais em condições de golfadas, onde a fração de vazio na sucção pode variar significativamente. Isto limita enormemente a janela operacional dos equipamentos. Uma forma de minimizar os efeitos das golfadas e, assim, ampliar a janela de operação destes equipamentos é a instalação de misturadores de fluxo na sucção das bombas, que atuam de forma a garantir uma maior sobrevida ao equipamento. Portanto, o projeto e a previsão do comportamento deste tipo de equipamento são fundamentais para bom funcionamento dos sistemas de bombeamento submarino. O presente trabalho investiga numericamente, com o modelo de dois fluidos, a eficiência de um tipo de misturador em uniformizar as frações de vazio. Diferentes configurações geométricas são analisadas e a influência das vazões de admissão de ambas as fases é discutida. A metodologia é validada através da comparação da queda de pressão através do misturador com dados experimentais disponíveis, onde se observou boa concordância. O modelo numérico mostra ainda que uma reserva de líquido é mantida no interior do equipamento e, o gás é forçado a se dispersar na corrente de líquido para sair do misturador. O comportamento do misturador frente à presença de golfadas também é investigado. Ao final do trabalho é proposta uma nova geometria, que se mostra mais tolerante a intermitências no escoamento. / [en] The offshore oil production is increasingly using pumping equipment at the seabed for production of wells at long distances from production units. Most of these devices have difficulty to operate in the presence of gas, especially in slug flow conditions, where the pump suction s void fraction can vary significantly. This problem limits the equipment s range of operation. One way to minimize the effects of slugging and thus enlarge the operation range of these devices is to use flow mixers at the pump s suction, which helps to ensure the operation even in the presence of large gas bubbles. Therefore, the design and prediction of the behavior of this type of equipment are essential for proper operation of subsea pumping systems. At the present work, the efficiency of a type of flow mixer to provide uniform void fractions at its outlet is numerically investigated, with the two fluid model. Different geometric configurations are analyzed and the influence of intake flow of both phases is discussed. The methodology is validated through comparison of the pressure drop through the flow mixer with available experimental data, where good agreement was observed. The numerical model also shows that a buffer of liquid is maintained inside the equipment and the gas is forced to disperse in the liquid stream to exit the mixer. The mixer s behavior in the presence of slugs is also investigated. Finally, a new geometry is proposed, which seems to be more efficient to avoid flow s intermittencies.

A Estenose de Canal Lombar (ECL) é caracterizada pela redução do espaço de elementos neurais ou vasculares da coluna lombar. Os sintomas incluem dor e/ou parestesia em membros inferiores, região lombar, e glúteos e Claudicação Intermitente Neurogênica. O tratamento conservador é a escolha inicial para o manejo de pacientes com ECL, por isso é importante a identificação de diferentes estratégias para o tratamento conservador, e a compreensão das alterações em parâmetros funcionais que estes tratamentos geram. O presente estudo objetivou comparar os efeitos de 24 sessões de Fisioterapia Aquática (GFA) e de Fisioterapia Solo (GFS) nos parâmetros espaço-temporais de marcha, equilíbrio, nível de dor percebida, incapacidade, capacidade física funcional, medo de movimento e níveis de depressão em indivíduos com ECL. Para observação das diferenças entre os grupos e momentos foi realizado o teste de Equações de Estimativa Generalizada no software SPSS versão 20.0. Para todas as análises o índice de significância adotado foi de 95% (α=0,05). Os níveis de incapacidade, dor, e estados depressivos reduziram, bem como a velocidade de caminhada autosselecionada e o índice de reabilitação locomotora aumentaram após as intervenções sem diferenças entre os grupos. O GFA apresentou melhora dos parâmetros espaço-temporais de marcha em velocidade fixa, redução da ingesta de medicação analgésica, e redução da média semanal de dor mais cedo que o GFS. O GFS demonstrou maior melhora da mobilidade funcional indicando um melhor equilíbrio após a intervenção em comparação ao GFA. Tratamentos fisioterapêuticos estruturados com associação de exercícios de estabilização de tronco, alongamentos e terapia manual mostram-se eficazes para melhora da incapacidade, dor, depressão e parâmetros de marcha em indivíduos com Estenose da Canal Lombar, sendo o meio aquático potencializador da resposta analgésica e da melhora em parâmetros espaço temporais de marcha e o solo potencializador da melhora do equilíbrio. / Lumbar Spinal Stenosis (LSS) is characterized by a reduction in the space of vascular and neuronal elements of the spinal canal space. Symptoms include pain and/or paresthesia in lower limbs, lumbar region and buttocks, and Neurogenic Intermittent Claudication. Conservative treatments are the choice for initial management of patients with LSS, therefore it is important to identify different conservative treatments strategies and understanding of the changes in functional parameters that those treatments cause. The present study aimed to compare the effects of 24 physiotherapy sections of Aquatic Physiotherapy (GFA) and Ground Physiotherapy (GFS) in spatiotemporal gait parameters, balance, perceived level of pain, disability, functional exercise capacity, fear of movement, and clinical depression in individuals with LSS. Generalized Estimating Equations were made to observe the differences between groups and moments on SPSS software version 20.0. For all tests, the significance level was 95% (α = 0,05). Disability, pain and depressive symptoms reduced and selfselected walking speed and locomotor rehabilitation index increased after interventions with no differences between groups. GFA improve spatiotemporal gait parameter in fixed speed, reduced analgesic medication, and show an earlier reduction in weekly pain. GFS improve functional mobility indicating a better balance in comparison to GFA. Physiotherapeutic treatments structured with the association of stabilization exercises, stretching exercises and manual therapy are efficient in improving disability, pain, depression and gait parameters in Lumbar Spinal Stenosis patients, water environment potentiate analgesic and spatiotemporal improvements, and land potentiate balance improvements.

Orientador: Prof. Dr. Roberto Venegeroles / Dissertação (mestrado) - Universidade Federal do ABC, Programa de Pós-Graduação em Física, 2015. / Discutiremos uma classe de sistemas dinâmicos intermitentes na qual o espaço de fase é composto de duas regiões distintas: uma região laminar, onde a partícula desenvolve uma dinâmica lenta e quase regular até saltar para uma região turbulenta, onde a mesma desenvolve uma dinâmica caó- tica de curta duração até ser reinjetada de volta para a fase laminar, num processo que assim se repete. A fase laminar é causada pela existência de medida invariante innita, e a composição regularidade-caos resulta numa modalidade de caos fraco na qual a separação de trajetórias inicialmente muito próximas torna-se subexponencial (em sistemas caóticos usuais, essa separação é exponencial). Por conta desse tipo intermitência, o mapa apresentará um comportamento ergódico diferente daquele observado pelo teorema de Birkho, de modo que a distribuição de médias temporais de observáveis (com fatores próprios de normalização) é descrita essencialmente por uma estatística Mittag-Leer, ao invés de distribuições com limites assintóticos para delta de Dirac. Apresentaremos a lei responsável por tal comportamento, o teorema de Aaronson-Darling-Kac, que nos permitirá estender adequadamente certos observáveis, tais como o expoente de Lyapunov e a entropia de Kolmogorov- Sinai, de modo a inferir precisamente a existência desse tipo de instabilidade. Após um estudo das principais características ergódicas de tais sistemas, investigamos o número de primeiras-passagens da fase laminar para a turbulenta, e como obter informações-chave por meio dessa quantidade. Mostraremos também que a teoria de processos de renovação, usualmente empregada na literatura para esse m, é insuciente para descrever precisamente esse tipo de intermitência. Historicamente, esse tipo de sistema surgiu do estudo de mapas de primeiro retorno de certas seções do atrator de Lorenz, realizado nos anos 80 por Pomeau e Manneville. Atualmente, cadeias de tais mapas são empregadas no estudo de difusão anômala e passeios aleatórios com tempos de espera. / We discuss a class of intermittent dynamical systems in which the phase space is made up of two distinct regions: a laminar region, where the particle develops a slow and almost regular dynamic until it jumps to a turbulent region, where it develops a chaotic dynamic of short duration that is reinjected back into the laminating step, in a repeating process. The laminar phase is caused by the existence of innite invariant measure, and the regularity-chaos composition results in a weak mode in which the trajectories separation of two initial nearly points becomes subexponential (in usual chaotic systems, this separation is exponential). Because of this type of intermittency, the map will present a dierent behavior from that observed by ergodic Birkho's theorem, so that the distribution of average observable time (with its own normalization factors) is described essentially by a Mittag-Leer statistics, rather than distributions with asymptotic limit to the Dirac delta. We will present the law responsible for such behavior, the theorem Aaronson-Darling-Kac, which will allow us to extend properly certain observables, such as the Lyapunov exponent and entropy Kolmogorov-Sinai, in order to infer precisely the existence of such instability . After a study of the main ergodic characteristics of such systems, we investigate the number of rst-passages of the laminar stage for the turbulence, and how to get key information by that amount. We will also show that the theory of renewal processes, usually used in the literature for this purpose, is insucient to accurately describe this type of intermittency. Historically, this type of system emerged from the study of rst return maps of certain sections of the Lorenz attractor was accomplished in the 80's by Pomeau and Manneville. Currently chains of these maps are used in the study of anomalous diusion and random walks with waiting times.