Osteoarthritis (OA) is a degenerative disease of the joint that leads to joint instability, degradation of the articular cartilage surface and eventually joint failure. Articular cartilage surfaces exhibit unique mechanical behaviors, bearing and distributing loads across joint surfaces, but have poor regenerative capacities. Human Mesenchymal Stem Cells (hMSCs) present a promising treatment to target OA, relying on their regenerative capacity and structural contributions to tissue repair, along with their immunomodulatory and anti-inflammatory properties. The multipotency of hMSCs allow these cells to differentiate towards osteogenic, chondrogenic and adipogenic lineages and directly incorporate into native tissue. hMSCs also possess the capacity to induce numerous paracrine-mediated processes including the recruitment of stem and progenitor cells, prevention of apoptosis, facilitation of beneficial remodeling and modulation of the immune response. Through encapsulating hMSCs, the effects of their paracrine action were studied directly, as the capsule presents a mechanical barrier for direct physical interaction and integration of these cells within the native tissue. The objective of this study was to utilize encapsulation of hMSCs to determine the paracrine effects of hMSCs on the progression of OA. OA was surgically induced in rats via the medial meniscus transection (MMT) surgery, which presents the phenotypical cartilage degradation associated with OA at 3 weeks. The efficacy of hMSC intervention was assessed using Lewis Rats with MMT (n=5 per group). Intra-articular injections of encapsulated hMSCs were given one day post-op and 3 weeks post-op for the 3-week and 6-week MMT studies, respectively. Animals were euthanized on the final day for both the immediate and delayed treatment studies. Micro-structural changes of the articular cartilage, osteophytes and subchondral bone of the medial tibial plateau were assessed using contrast enhanced microCT. We hypothesized that the intra-articular delivery of encapsulated hMSCs will have a positive effect, via paracrine-mediated action, on the onset and development of OA. The capsules also have the potential to improve retention and cell viability in the knee joint space. Each of these factors could contribute to enhanced therapeutic potential of the hMSC treatment. Utilizing NIR labeled sodium alginate capsules, a retention profile for the capsules yielded a tau value of 11.48 days, whereas previous studies have shown scaffold free hMSCs show complete clearance in 7 days. The 3-week MMT, run to analyze the effects of immediate treatment of encapsulated hMSCs on the onset of OA, showed a trend towards decreased cartilage thickness and a decreased surface roughness for the hMSC group in comparison to the Saline group, specifically. Additionally, the hMSC group showed a trend towards increased mineralized osteophyte volume for the hMSC group in comparison to the Saline group. Analysis of the subchondral bone yielded no differences between the hMSC and Saline groups for bone morphology. The 6 week MMT study was run to analyze the effects of a delayed treatment of encapsulated hMSCs on OA after the disease had developed. This study showed a similar result with the immediate treatment study for surface roughness, with the hMSC group showing a decrease in comparison to the Saline group. However, no differences were noted for cartilage thickness between the two respective groups. To further analyze the cartilage in the later stages of OA, exposed bone was quantified yielding a trend towards decreased exposed bone in the hMSC group in comparison to the Saline group. The mineralized osteophyte volume for the hMSC group, of the delayed treatment study, yielded a significantly higher value than all other groups. Additionally, the subchondral bone of the hMSC group trended towards a decreased porosity in comparison to the Saline group. This is one of the first studies to use sodium alginate encapsulation of hMSCs as an innovative scaffold means for intra-articular injections into the knee space. Encapsulated hMSCs permitted not only enhanced cellular retention in the knee space but showed a potential chondroprotective role of the paracrine signaling properties of hMSCs in the early stages of OA. These advantages of encapsulated hMSCs were countered by enhancements of secondary OA phenotypic changes, mainly increased mineralized osteophyte volume and a trend towards increased subchondral bone sclerosis in the later stages of OA. hMSCs have shown great potential as disease modifying drugs and through this study we have further explored the efficacy of these drugs for future treatments of OA. This study has high clinical relevance and with clinical practice running well ahead of current scientific evidence, it is imperative that these findings be considered not only in pre-clinical work but in current and future clinical trials. / 2018-07-11T00:00:00Z

Grâce au progrès de la chimiothérapie systémique, la prise en charge de la carcinose péritonéale a connu une révolution avec le développement de la chirurgie de cytoréduction. L'association d'une chirurgie de cytoréduction à une chimiothérapie systémique et intra-péritonéale a permis de proposer à certains patients sélectionnés un traitement à visée curative et représente le traitement de référence pour la plupart des carcinoses d'origine non gynécologique. Toutes les carcinoses et tous les patients sont différents, c'est pourquoi de nombreux travaux ont permis de préciser les facteurs permettant la sélection des patients pouvant bénéficier d'un tel traitement. Le principal facteur pour proposer un traitement curatif d'une carcinose péritonéale est la possibilité de réaliser une résection complète. Malgré ces progrès dans le traitement et la sélection des patients, les résultats restent insuffisants et trop peu de patients présentent une maladie résécable accessible à un traitement curatif. L'apparition des biothérapies et notamment les anti-VEGF offre une nouvelle voie de recherche. Le bevacizumab, anticorps anti-VEGF, a montré une efficacité significative dans le traitement des maladies métastatiques. Il augmente l'efficacité du traitement par chimiothérapie systémique. Le VEGF semble également présenter un rôle important dans le développement et l'agressivité des carcinoses péritonéales. Pour permettre d'augmenter l'efficacité du traitement curatif des carcinoses péritonéales, se discute d'associer du bevacizumab. Cependant, administré par voie systémique il peut majorer la morbidité faisant contre-indiquer son association avec une chirurgie abdominale lourde déjà grevée d'une morbidité importante. L'hypothèse qui a justifié ce travail est que l'administration intra-péritonéale de bevacizumab pourrait augmenter la résécablité et la survie des patients atteints par une carcinose péritonéale d'origine non gynécologique en limitant la morbidité. Le but de ce travail est au travers d'études cliniques et expérimentales d'évaluer la faisabilité et l'efficacité d'un traitement par bevacizumab intra-péritonéale en association au traitement chirurgical de référence pour la prise en charge des CP d'origine non gynécologique / Advances in systemic chemotherapy permitted revolution in the management of peritoneal carcinomatosis with the development of cytoreductive surgery. The combination of cytoreductive surgery with systemic and intraperitoneal chemotherapy offer to selected patients a hope of cure and is considered as the treatment of choice for most carcinomatosis of non-gynecological origin. All carcinomatosis and all patients are different and numerous studies tried to determine factors for selecting patients eligible for such treatment. The mains prognostic factor for curative treatment is the ability to perform a complete cytoreduction. Despite these advances in the treatment and selection of patients, the results are still insufficient and few patients have resectable disease accessible to a cure. The development of biotherapies including anti -VEGF provides a new way of research. Bevacizumab, anti - VEGF antibody, showed significant efficacy in the treatment of metastatic diseases. It increases the efficiency of treatment by systemic chemotherapy. VEGF appears to have an important role in the development and aggressiveness of peritoneal carcinomatosis. To increase the effectiveness of curative treatment of peritoneal carcinomatosis, the combination of bevacizumab to the current standard treatment can be proposed. The bevacizumab administered intravenously may increase morbidity prohibiting its association with major abdominal surgery already burdened with significant morbidity. The hypothesis of this work is that the intraperitoneal administration of bevacizumab may increase resectability and survival of patients with peritoneal carcinomatosis of non- gynecologic origin and limit the morbidity. The aim is through clinical and experimental studies to evaluate the feasibility and the efficacy of treatment with intraperitoneal bevacizumab in combination with standard surgical treatment of peritoneal surface malignancy

O presente trabalho avalia a variação não-geográfica de Necromys lasiurus (Lund, 1840) dentro do território brasileiro, utilizando a morfometria craniana. Os dados foram obtidos a partir de 20 medidas craniodentárias tomadas de 1.572 indivíduos depositados em diversas coleções brasileiras. Foram descritas classes etárias baseadas exclusivamente no desgaste dos molares superiores e as mesmas foram utilizadas como índices etários para a avaliação da variação etária. Foram realizadas análises uni e multivariadas para descrever a variação sexual e etária de N. lasiurus considerando primeiramente toda a amostra e, em seguida, separadamente para cada localidade ou agrupamento cujo número amostral se mostrou suficiente para a condução dos testes estatísticos. N. lasiurus revelou dimorfismo relacionado às classes etárias intermediárias tanto na amostra total quanto nas amostras locais. No entanto, a ocorrência de dimorfismo sexual não se repetiu em todas as localidades avaliadas. A análise da variação etária com a amostra total revelou importantes padrões de variação craniana, como o rápido desenvolvimento da região orofacial em relação a outras regiões do crânio. No entanto, a avaliação da ontogenia nas amostras locais revelou diversos padrões ontogenéticos distintos. Além disso, as análises multivariadas apontam para a existência de uma estruturação geográfica da variação, corroborando estudos anteriores com a espécie. Os resultados obtidos indicam que futuras análises de cunho geográfico e taxonômico sobre N. lasiurus devem abordar os sexos de maneira separada e as classes etárias podem ser homogeneizadas para a formação de amostras com indivíduos suficientes para permitir a realização de análises estatísticas. / The present study assess the non-geographic variation of Necromys lasiurus (Lund, 1840) in Brazil, using skull morphometrics. A total of 20 craniometric measurements were taken from 1,572 specimens deposited in many Brazilian zoological collections. Age classes were described based on the wear stage of the superior molars and used as index to asses the variation due to age. Uni and multivariate analyses were used in order to describe the sexual and ontogenetic variation of N. lasiurus, first using the total sample and then using geographic samples that contained sufficient individuals for the application of the statistical tests. N. lasiurus presented sexual dimorphism related to intemediate age classes in total and in some local samples. The age assessment revealed important ontogenetic patterns of the skull development, like the rapid growth of orofacial region compared to other parts. The local analyses revealed individual patterns of variation for each sample. Besides, the multivariate approach showed geographic patterns of variation, just like previous studies said. The results of this study indicate that future geographic and taxonomic investigations on N. lasiurus should keep both sexes separated and the age classes could be homogenized in order do form adequate samples that allow the application of statistical tests.

This thesis is concerned with a fundamental unit of the economy: Households. Even in advanced economies, upwards of 70% of the population live in households composed of multiple people. A large number of decisions are taken at the level of the household, that is to say, they are taken jointly by household members: How to raise children, how much and when to work, how many cartons of milk to purchase. How these decisions are made is therefore of great importance for the people who live in them and for their well-being.But precisely because household members make decisions jointly it is hard to know how they come about and to what extent they benefit individual members. This is why households are often viewed as unique decision makers in economics. Even if they contain multiple people, they are treated as though they were a single person with a single set of preferences. This unitary approach is often sufficient and can be a helpful simplification. But in many situations it does not deliver an adequate description of household behavior. For instance, the unitary model does not permit the study of individual wellbeing and inequality inside the household. In addition, implications of the unitary model have been rejected repeatedly in the demand literature.Bargaining models offer an alternative where household members have individual preferences and come to joint decisions in various ways. There are by now a great number of such models, all of which allow for the study of bargaining power, a measure of the influence a member has in decision making. This concept is important because it has implications for the welfare of individuals. If one household member’s bargaining power increases, the household’s choices will be more closely aligned with that member’s preferences, ceteris paribus.The three chapters below can be divided into two parts. The first part consists of Chapter 1, which looks to detect the influence of intra-household bargaining in a specific set of consumption choices: Consumption of the arts. The research in this chapter is designed to measure aspects of the effect of bargaining power in this domain, but does not seek to quantify bargaining power itself or to infer economic well-being of household members.Precisely this last point, however, is the focus of the second part of the thesis, consisting of Chapters 2 and 3. These focus specifically on the recovery of one measure of bargaining power, the resource share. Resource shares have the advantage of being interpretable in terms of economic well-being, which is not true of all such measures. They are estimated as part of structural models of household demand. These models are versions of the collective model of household decision making.Pioneered by Chiappori (1988) and Apps and Rees (1988), the collective model has become the go-to alternative to unitary approaches, where the household is seen as a single decision-making unit with a single well-behaved utility function. Instead, the collective model allows for individual utility functions for each member of the household. The model owes much of its success to the simplicity of its most fundamental assumption: That whatever the structure of the intra-household bargaining process, outcomes are Pareto-efficient. This means that no member can be made better off, without making another worse off. Though the model nests unitary models as special cases, it does have testable implications.The first chapter of the thesis is entitled “Household Decisions on Arts Consumption” and is joint work with Caterina Mauri, who has also collaborated with me on many other projects in her capacity as my girlfriend. In it, we explore the role of intra-household bargaining in arts consumption. We do this by estimating demand for various arts and cultural events such as the opera or dance performances using a large number of explanatory variables. One of these variables plays a special role. This variable is a distribution factor, meaning that it can be reasonably assumed to affect consumption only through the bargaining process, and not by modifying preferences. Such variables play an important role in the household bargaining literature. Here, three such variables are used. Among them is the share of household income that is contributed by the husband, the canonical distribution factor.The chapter fits into a literature on drivers of arts consumption, which has shown that in addition to such factors as age, income and education, spousal preferences and characteristics are important in determining how much and which cultural goods are consumed. Gender differences in preferences in arts consumption have also been shown to be important and to persist after accounting for class, education and other socio-economic factors (Bihagen and Katz-Gerro, 2000).We explore to what extent this difference in preferences can be used to shed light on the decision process in couples’ households. Using three different distribution factors, we infer whether changes in the relative bargaining power of spouses induce changes in arts consumption.Using a large sample from the US Current Population Survey which includes data on the frequency of visits to various categories of cultural activities, we regress atten- dance rates on a range of socio-economic variables using a suitable count data model.We find that attendance by men at events such as the opera, ballet and other dance performances, which are more frequently attended by women than by men, show a significant influence of the distribution factors. This significant effect persists irrespec- tively of which distribution factor is used. We conclude that more influential men tend to participate in these activities less frequently than less influential men, conditionally on a host of controls notably including hours worked.The second chapter centers around the recovery of resource shares. This chapter is joint work with Denni Tommasi, a fellow PhD student at ECARES. It relies on the collective model of the household, which assumes simply that household decisions are Pareto-efficient. From this assumption, a relatively simple household problem can be formulated. Households can be seen as maximizers of weighted sums of their members’ utility functions. Importantly the weights, known as bargaining weights (or bargaining power), may depend on many factors, including prices. The household problem in turn implies structure for household demand, which is observed in survey data.Collective demand systems do not necessarily identify measures of bargaining power however. In fact, the ability to recover such a measure, and especially one that is useful for welfare analysis, was an important milestone in the literature. It was reached by (Browning et al. 2013) (henceforth BCL), with a collective model capable of identi- fying resource shares (also known as a sharing rule). These shares provide a measure of how resources are allocated in the household and so can be used to study intra- household consumption inequality. They also take into account that households gen- erate economies of scale for their members, a phenomenon known as a consumption technology: By sharing goods such as housing, members of households can generate savings that can be used elsewhere.Estimation of these resource shares involves expressing household budget shares functions of preferences, a consumption technology and a sharing rule, each of which is a function of observables, and letting the resulting system loose on the data. But obtaining such a demand system is not free. In addition to the usual empirical speci- fications of the various parts of the system, an identifying assumption has to be made to assure that resource shares can be recovered in estimation. In BCL, this is the assumption that singles and adult members of households share the same preferences. In Chapter 2, however, an alternative assumption is used.In a recent paper, Dunbar et al. (2013) (hereafter DLP) develop a collective model based on BCL that allows to identify resource shares using assumptions on the simi- larity of preferences within and between households. The model uses demand only for assignable goods, a favorite of household economists. These are goods such as mens’ clothing and womens’ clothing for which it is known who in a household consumes them. In this chapter, we show why, especially when the data exhibit relatively flat Engel curves, the model is weakly identified and induces high variability and an im- plausible pattern in least squares estimates.We propose an estimation strategy nested in their framework that greatly reduces this practical impediment to recovery of individual resource shares. To achieve this, we follow an empirical Bayes method that incorporates additional (or out-of-sample) information on singles and relies on mild assumptions on preferences. We show the practical usefulness of this strategy through a series of Monte Carlo simulations and by applying it to Mexican data.The results show that our approach is robust, gives a plausible picture of the house- hold decision process, and is particularly beneficial for the practitioner who wishes to apply the DLP framework. Our welfare analysis of the PROGRESA program in Mexico is the first to include separate poverty rates for men and women in a CCT program.The third Chapter addresses a problem similar to the one discussed in Chapter 2. The goal, again, is to estimate resource shares and to remedy issues of imprecision and instability in the demand systems that can deliver them. Here, the collective model used is based on Lewbel and Pendakur (2008), and uses data on the entire basket of goods that households consume. The identifying assumption is similar to that used by BCL, although I allow for some differences in preferences between singles and married individuals.I set out to improve the precision and stability of the resulting estimates, and so to make the model more useful for welfare analysis. In order to do so, this chapter approaches, for the first time, the estimation of a collective household demand system from a Bayesian perspective. Using prior information on equivalence scales, as well as restrictions implied by theory, tight credible intervals are found for resource shares, a measure of the distribution of economic well-being in a household. A modern MCMC sampling method provides a complete picture of the high-dimensional parameter vec- tor’s posterior distribution and allows for reliable inference.The share of household earnings generated by a household member is estimated to have a positive effect on her share of household resources in a sample of couples from the US Consumer Expenditure survey. An increase in the earnings share of one percentage point is estimated to result in a shift of between 0.05% and 0.14% of household resources in the same direction, meaning that spouses partially insure one another against such shifts. The estimates imply an expected shift of 0.71% of household resources from the average man to the average woman in the same sample between 2008 and 2012, when men lost jobs at a greater rate than women.Both Chapters 2 and 3 explore unconventional ways to achieve gains in estimator precision and reliability at relatively little cost. This represents a valuable contribution to a literature that, for all its merits in complexity and ingenious modeling, has not yet seriously endeavored to make itself empirically useful. / Doctorat en Sciences économiques et de gestion / info:eu-repo/semantics/nonPublished

A diabetes mellitus (DM) causa alterações em todas as camadas da córnea. Córneas de pacientes diabéticos têm controle de sua hidratação prejudicado e são mais propensas à descompensação após injúria. A uveíte faco-induzida (UFI) ocorre em grandes proporções associada à catarata hipermatura em cães. A UFI também acarreta danos ao endotélio da córnea e pode levar ao edema estromal, usualmente transitório. Cães diabéticos são particularmente predispostos ao desenvolvimento de catarata e UFI associada. Os efeitos da DM e UFI podem potencialmente vir a se somar em córneas de cães com catarata diabética. A pressão intra-ocular (PIO) e paquimetria podem ser ferramentas úteis na determinação dessas alterações. O objetivo deste estudo foi determinar a relação entre pressão intra-ocular e paquimetria nos diferentes estágios de desenvolvimento das cataratas diabéticas e não diabéticas em cães da raça Poodle. Cento e vinte e dois cães adultos da raça Poodle, 134 fêmeas e 99 machos, com idades de 2 a 16 anos, foram admitidos no Serviço de Oftalmologia do Hospital Veterinário da Universidade de São Paulo e incluídos no trabalho. Afecções oculares concomitantes, ou doenças sistêmicas com manifestação ocular, foram consideradas fatores de exclusão. Após exame clínico oftalmológico, coletou-se dados referentes ao tempo de leucocoria e tempo de desenvolvimento da DM. Os cães tiveram a PIO mensurada por meio do TonoPen-XL® e a paquimetria mensurada com o uso do PachPen®. Para isso realizou-se anestesia tópica (colírio de Proximetacaína a 0,5% - Anestalcon®, Alcon). As comparações estatísticas entre as variáveis foram realizadas utilizando os testes de Spearman, Mc-Nemar e Mann-Whitney quando apropriados. As distribuições das variáveis entre os grupos foram avaliadas pelo test de Kruskal-Wallis, e quando significantes, o teste de Dunn foi utilizado para descriminar as diferenças encontradas. O nível de significância foi estabelecido em p<0,05. Dos 122 cães, 233 olhos foram incluídos e classificados em grupo controle (n=39), catarata incipiente (n=20), imatura (n=29), matura (n=20), hipermatura (n=80), catarata diabética imatura (n=9), diabética matura (n=11) e diabética hipermatura (n=25). As distribuições das variáveis (sexo, idade, peso, presença de uveíte, tempo de leucocoria, PIO e paquimetria) foram estatisticamente diferentes entre os diversos grupos. Fêmeas apresentaram-se mais acometidas por catarata diabética. A idade média dos animais variou de 7,03 a 10,73 anos entre os grupos, e os animais diabéticos foram estatisticamente mais velhos. A PIO foi estatisticamente menor e os sinais clínicos de UFI mais prevalentes nos grupos de cataratas hipermaturas, tanto diabéticas, quanto não diabéticas. A PIO correlacionou-se negativamente com a idade e a paquimetria. Houve correlação positiva da paquimetria com a idade e o peso; e correlação negativa com o tempo de leucocoria e a PIO. Olhos acometidos por UFI tiveram PIO estatisticamente menor e paquimetria maior, com diferença de 2 mmHg e 60 µm, respectivamente. Nos cães acometidos por catarata diabética, a paquimetria encontrou-se particularmente aumentada, e a UFI particularmente presente. Esse aumento possivelmente reflete a somatória dos efeitos da DM e UFI sobre a córnea. A hipermaturidade foi correlacionada à presença da UFI. A PIO e paquimetria mostraram-se instrumentos valiosos na determinação da UFI, principalmente se forem negativamente correlacionadas entre si. / Diabetes mellitus (DM) causes different alterations in all corneal layers, such as deficient control of hydration, what makes them prone to decompensate after injury. Lens induced uveitis (LIU) occurs mainly in dogs presenting hypermature cataracts, what causes irreversible damages to the corneal endothelium and may lead to stromal edema, usually transient. DM dogs are particularly predisposed to cataract with LIU associated. Intraocular pressure (IOP) and pachymetry measurements may be useful procedures capable to detect such alterations. The aim of this study was to determinate the relationship between intraocular pressure and pachymetry on diabetic and nondiabetic Poodles, presenting different stages of cataracts. One hundred twenty-two Poodles, 134 females and 99 males, with ages varying from 2 to 16 years, were admitted at the Ophthalmology Service, of the Veterinary Hospital, of the University of São Paulo. After complete identification of the animals, anamnese (time of DM and cataract formation) and ophthalmological exam, dogs were included in the study. Dogs affected by other systemic diseases inducing ocular manifestation or other primary ocular alteration were excluded. LIU was diagnosed by observation of congestion of the episcleral vases and resistence to midriasis after induction with Mydriacyl®. IOP was measured by TonoPen-XL® and pachymetry by PachPen® after instillation of anesthetic eyedrop (Proximetacaine 0,5% - Anestalcon, Alcon). Statistical comparison between factors were made using Spearman, Mc-Nemar and Mann-Whitney tests when appropriated. The distributions of the factors among the groups were compared by Krusskal-Walliss test, and when significant, Dunns test was used to describe the differences found. The level of significance was set at p<0,05. Two hundred thirty-three eyes of 122 Poodles were evaluated. Eyes were classified in different groups: healthy dogs without cataracts (n=39); dogs presenting incipient cataract (n=20); with immature cataracts (n=29); mature cataracts (n=20); or hypermature cataracts (n=80); DM dogs presenting immature cataract (n=9); DM with mature cataracts (n=11); and DM with hypermature cataracts (n=25). Distribution of factors, such as age, sex, weight, time of DM and cataract, presence of LIU, IOP and pachymetry were statistically different between groups. Female Poodles were more affected by diabetic cataract and diabetic dogs were older than the other ones. IOP was statistically lower and LIU alterations more prevalent in the hypermature cataract groups (diabetic and no diabetics). IOP was negatively correlated to age and pachymetry measures. Pachymetry was positively correlated to age and weight. Negative correlation was observed between pachymetry and time of cataracts formation. LIU eyes presented lower IOP and higher pachymetry. The difference found at pachymetry and IOP measurements in LIU and non LIU eyes were 60 µm and 2 mmHg respectively. In diabetic dogs, pachymetry was particularly higher and LIU particularly present. The higher corneal thickness may possible be related to the sum of alterations caused by DM and LIU to those corneas. Hypermaturity was directly related to LIU. We concluded that pachymetry and IOP measurements are important procedures to the LIU diagnosis, mainly when negatively correlated.

O tratamento da catarata em cães têm passado por algumas mudanças. A facoemulsificação reduziu o tempo cirúrgico e a necessidade de incisão extensa; o implante de lentes intra-oculares (LIOs) permitiu restabelecer a emetropia após a remoção do cristalino. O processo inflamatório induzido pelas cirurgias intra-oculares leva a um estado de estresse oxidativo, com efeitos deletérios às estruturas oculares. O presente estudo teve como objetivo avaliar comparativamente o estresse oxidativo após facoemulsificação experimental em cães, com e sem implante de LIO. Doze cães (três machos e nove fêmeas), sem raça definida, com peso médio de 15,8kg, foram submetidos à facoemulsificação bilateral, sendo doze olhos sem implante de LIO (Grupo 1) e doze olhos com implante de LIO de polimetilmetacrilato no saco capsular (Grupo 2). Os animais foram medicados nos períodos pré-operatório e pós-operatório com antiinflamatórios, antibióticos e midriáticos. As amostras de humor aquoso (HA) foram obtidas por paracentese de câmara anterior, sob anestesia geral, nos períodos pré-operatório (T0) e pós-operatório com 1 dia (T1), 2 dias (T2), 3 dias (T3), 7 dias (T7) e 14 dias (T14). O estresse oxidativo foi avaliado por meio da determinação quantitativa de proteínas no HA (método de Lowry), avaliação da atividade antioxidante total do HA utilizando o AAPH, cloreto de 2,2'azobis (2-metilamidinopropano) e avaliação da concentração de ácido ascórbico no HA e no plasma (cromatografia líquida de alta eficiência). Os resultados foram submetidos à análise estatística, utilizando-se o teste t de Student, quando as variáveis apresentaram distribuição normal, e pelo teste de Wilcoxon, quando não houve distribuição normal. Os níveis de proteína total no HA aumentaram nos dois grupos, sendo de forma mais acentuada no Grupo 2 em todos os tempos pós-operatórios: T1 (p= 0,004), T2 (p= 0,002), T3 (p= 0,004), T7 (p= 0,003) e T14 (p= 0,009). A atividade antioxidante total do HA apresentou uma diminuição nos dois grupos, mais acentuada, entretanto, no Grupo 2, com diferença estatisticamente significante nos tempos T1 (p= 0,013), T2 (p= 0,016), T3 (p= 0,002) e T14 (p= 0,033). No tempo T7 (p= 0,155) essa diferença não foi observada. A concentração de ácido ascórbico no HA apresentou uma diminuição marcante no primeiro dia do pós-operatório, seguida por uma recuperação progressiva nos dois grupos. O Grupo 2 mostrou resultados mais baixos, com diferença estatisticamente significante nos tempos T1 (p= 0,003), T3 (p= 0,015), T7 (p= 0,004) e T14 (p= 0,007), exceto em T2 (p= 0,051), quando não houve diferença. A concentração de ácido ascórbico no plasma não variou em função dos procedimentos. A comparação entre os procedimentos sugere que o implante de LIO contribui para a condição de estresse oxidativo. / The cataract treatment in dogs has undergone some changes. Phacoemulsification has reduced the surgical time of cataract extraction and the need of large incision. Intraocular lens (IOL) implantation has allowed emetropic vision recovery. The inflammatory process induced by intraocular surgery leads to an oxidative stress, with ocular structures damage. The purpose of this study was to comparatively evaluate the oxidative stress following phacoemulsification in dogs with and without IOL implantation. Twelve dogs, three male and nine female, mixed breed, with an average weight of 15.8kg were submitted to bilateral phacoemulsification, being twelve eyes without IOL implantation (Group 1) and twelve eyes with polymethylmethacrylate IOL in the capsular bag (Group 2). In the pre-operative and post-operative periods, the medication consisted of anti-inflammatories, antibiotics and mydriatics. Aqueous humor (AH) samples were taken by anterior chamber paracentesis, under general anesthesia in the pre-operative (T0) and post-operative periods after 1 (T1), 2 (T2), 3 (T3), 7 (T7) and 14 (T14) days of the surgery. The oxidative stress was evaluated by quantitative protein levels in the AH (Lowry’s method), total antioxidant activity in the AH using 2,2’ azobis (2-methylpropionamidine) dihydrochloride (AAPH) and ascorbic acid concentration in the AH and plasma (high performance liquid chromatography). Results were submitted to statistical analysis using the t-student test when the variables had a normal distribution and Wilcoxon test when they did not. Aqueous humor total protein levels increased in both groups, more intensively in Group 2 in all post-operative periods: T1 (p= 0.004), T2 (p= 0.002), T3 (p= 0.004), T7 (p= 0.003) and T14 (p= 0.009). Total antioxidant activity in the AH decreased in both groups; however, it was more impressive in Group 2, with statistical significant difference in T1 (p= 0.013), T2 (p= 0.016), T3 (p= 0.002) e T14 (p= 0.033). In T7 (p= 0.155), this difference was not observed. Ascorbic acid concentration in the AH presented a remarkably decrease in the first post-operative day, then started to recover progressively in the two groups. Group 2 showed lower results with statistically significant differences in T1 (p= 0.003); T3 (p= 0.015); T7 (p= 0.004) and T14 (p= 0.007), except in T2 (p= 0.051) when there was no difference. Ascorbic acid concentration in plasma did not vary as a result of the procedures. The comparison between procedures suggests that IOL implantation contributes to an oxidative stress condition.

Este trabalho teve como objetivo estudar um caso específico de epilepsia refratária causada por uma má formação no tecido cerebral, denominada displasia cortical focal (DCF). Por ser uma má formação no cérebro, suas consequências aparecem desde a infância, em que ela, a DCF, é a principal causadora das epilepsias de caso refratário. O mapeamento da região com DCF geralmente é feito por meio de imagens de ressonância magnética em conjunto com outras técnicas, como, por exemplo, o PET (positron emission tomography), o EEG (eletroencefalograma) intracraniano, entre outras. Contudo, por serem técnicas muito caras, de difícil realização ou muito invasivas, e por sabermos que as regiões displásicas possuem uma rigidez diferente da do restante do cérebro, foi proposto nesta dissertação o estudo desses casos utilizando uma técnica barata, simples, não invasiva e sensível à rigidez tecidual, a elastografia por ultrassom, na qual, para causar a deformação do tecido cerebral, foram usadas próprias artérias internas do cérebro. Para tal estudo, criamos um algoritmo de processamento de dados com uma interface gráfica GUI (graphical user interface) capaz de mudar os parâmetros de processamento e ver seus resultados em tempo real. Em seguida, esse algoritmo foi estudado em um ambiente controlado em material mimetizador de tecido biológico (phantom), no qual construímos um bloco de 10 x 10 x 12cm3, preenchido com material que mimetiza as propriedades mecânicas e acústicas do tecido mole e inserimos nele uma bexiga canudo preenchida com um uido simulador de sangue e uma inclusão mais rígida do que a base do material, posicionada acima do canudo. Foi utilizado, também, um acionador mecânico pulsátil para simular a pulsação mecânica equivalente à pulsação sanguínea da artéria cerebral. Foram feitas imagens elastográcas e de velocidade utilizando somente a deformação causada pelo deslocamento da bexiga, no interior do phantom, e, através de uma transformada de Fourier, foi calculado o período de pulsação da bexiga. Vimos que as imagens elastográcas e de velocidade foram capazes de localizar a inclusão, e o processamento temporal pode nos mostrar com precisão a frequência de pulsação da bexiga canudo. Finalizada essa etapa laboratorial, zemos o mesmo procedimento, porém in vivo, para dois casos: um com DCF tipo III-B, no qual não enxergávamos nada no modo B; e outro com tipo II-B, no qual foi observado uma diferença de impedância mecânica pelo modo B. As imagens foram coletadas durante o procedimento cirúrgico pelo próprio cirurgião usando um transdutor microconvexo acoplado a uma plataforma de ultrassom, modelo Sonix RP, e processadas num segundo momento. Vimos, no primeiro caso, pelas imagens elastográcas, as regiões mais rígidas, supostamente displásicas, que não estavam aparecendo no modo B e, no segundo caso, uma região maior do que a apresentada no modo B. Nossos resultados das medidas de frequência da pulsação arterial, para ambas as situações, 61; 5BPM e 91BPM, caram bastante próximos do valor medido com o eletrocardiograma durante a coleta do sinal, 65BPM e 94BPM, respectivamente. Por meio dos resultados da análise histológica, pudemos conrmar que o que estávamos enxergando com nosso programa era realmente uma região displásica. Dessa forma, concluímos que nosso algoritmo funcionou bem para esses casos clínicos. / The mainly goal of this work was to study a specic case of refractory epilepsy generated by a malformation in the brain tissue, called focal cortical dysplasia (FCD). Due the fact it is a brain malformation its eects show up since the childhood where it is the principal epilepsy generator. The mapping of this region is usually made by magnetic resonance images with another technique, such as, for instance, the PET (position emition tomography), the EEG (electrocardiogram), and others. However, for the fact that these techniques are expensive, dicult to perform or invasive, and knowing that the dysplastic regions are stier than the regular brain tissue, it was proposed in this dissertation the use of ultrasound elastography as a cheaper, simpler and noninvasive image modality capable to detect dierences in the tissue stiness of the FCD region. To generate the strain in the brain tissue it was used the pulsation of the local arteries. To achieve our goal, we created a data processing algorithm in MATLAB with a graphic user interface (GUI) capable to change the processing parameters to see its results in real time. This algorithm was tested in phantom using a block of tissue mimicking material (10 x 10 x 12 cm3). A balloon of latex led with a blood mimicking uid was immersed in the middle of the phantom and a cylindrical inclusion of 1 cm of diameter was immersed above the balloon. The bulb of the balloon was keep outside of the phantom to be mechanically pressured by a dedicated magnetic actuator, simulating the mechanical pulsation of the brain arteries. The velocity and elastography images were studied using just the strain caused by the displacement of the wall of the balloon tube inside the phantom. The period of pulsation was precisely calculated from these images. After that, we did the same procedure in two in vivo cases: one with FCD type III-B; and the other with FCD type II-B. All our intraoperative images were acquired for the surgeons using a micro convex transducer linked to an Ultrasound platform (Sonix RP) and, then, processed o-line. In the B mode scanning we didnât see any formation inside the brain for the rst case, and for the second, we did. In the elastographic images we saw a clearly stiffer region in the rst case that was invisible in the B mode; and for the second case, we saw a bigger stiffer region than we saw in the B mode imaging too. And for both results, the arteria pulsation frequency, 61.5 BPM and 91 BPM, were veryclose to the measured value collected in the electrocardiogram during the surgery, 65 BPM and 94 BPM, respectively. Analyzing the histological results we could conrm that what we were showing in our elastographic images were FCD, indeed. Thereby we concluded that our algorithm had worked in these clinical data.

O trabalho tem por objetivo a análise do tema da arbitragem societária, entendida aqui como a arbitragem decorrente de cláusula arbitral inserida no ato constitutivo de uma sociedade. Analisa-se, num primeiro momento, a adequação da arbitragem em matéria societária, o que compreende a investigação de suas vantagens e desvantagens em relação à justiça estatal e de algumas consequências da escolha da via arbitral para os sujeitos envolvidos. Num segundo momento, trata-se do cabimento da arbitragem em matéria societária, o que compreende o estudo da arbitrabilidade dos pontos de vista subjetivo e objetivo. A arbitrabilidade subjetiva é tema que envolve a polêmica sobre a vinculação de sócios que não concordem expressamente com a cláusula arbitral inserida mediante deliberação majoritária. Feito isso, o trabalho ruma para temas sensíveis de aplicação da arbitragem societária: (i) a possível instituição de quórum qualificado e direito de recesso ao acionista para a inserção de cláusula compromissória no ato constitutivo de sociedade; (ii) a vinculação dos órgãos sociais e de seus titulares à cláusula arbitral societária; (iii) a confidencialidade; (iv) as questões procedimentais decorrentes da multiplicidade de sujeitos envolvidos; e (v) o julgamento de impasses de natureza negocial pelos árbitros. Ao final, pretende-se verificar se algum desses pontos merece regulação legal. / The work aims to analyze the subject of intra-corporate arbitration, understood here as arbitration derived from arbitration clauses inserted in articles of association of companies. It analyses, at first, the appropriateness of arbitration for corporate disputes, which encompasses investigation about the advantages and disadvantages of arbitration compared to state justice and some consequences of the choice of arbitration for subjects involved. Secondly, investigation focuses in arbitrability (both from a subjective and an objective perspective). From a subjective perspective, investigation concerns the controversy about the possibility of imposing the arbitration clause inserted in articles of incorporation by the majority of the partners or shareholders against the will of those who do not agree expressly with the arbitration clause. Later, the work aims to analyze some sensitive issues concerning the implementation of intra-corporate arbitration: (i) the possible creation of qualified quorum and withdrawal rights for the partners or shareholders that do not agree with the arbitration clause imposed by the majority; (ii) the possibility to impose the arbitration clause against corporate bodies and its members; (iii) confidentiality; (iv) some procedural issues derived from multiple people involved in litigation about the same subject matter; (v) the possibility for arbitrators to judge controversies related to business matters. The final purpose is to determine whether any of these controversial topics should have legal regulation.

INTRODUÇÃO: O blefaroespasmo essencial é uma distonia focal caracterizada por contrações involuntárias, espasmódicas e bilaterais dos músculos protratores das pálpebras. O glaucoma é a principal causa de cegueira irreversível em adultos de países desenvolvidos e a elevação da pressão intra-ocular é o maior fator de risco para o desenvolvimento da doença. A contração voluntária forçada das pálpebras pode causar aumentos da pressão intra-ocular de até 90 mmHg. Uma vez que pacientes com blefaroespasmo essencial apresentam contrações palpebrais freqüentes e de forte intensidade, eles poderiam compor um grupo de risco para o desenvolvimento do glaucoma. MÉTODOS: Vinte e oito pacientes com blefaroespasmo essencial e 28 pacientes de grupo controle, formado por indivíduos com doenças palpebrais ou no seu pós-operatório, foram submetidos a um exame oftalmológico completo. No grupo de pacientes com blefaroespasmo, a avaliação foi realizada em 8 a 11 dias após o tratamento com toxina botulínica. Efetuou-se exame de refração e medida de melhor acuidade visual corrigida com tabela de Snellen, biomicroscopia em lâmpada de fenda, tonometria de aplanação, campo visual computadorizado, teste de sobrecarga hídrica e biomicroscopia de fundo para avaliação da papila óptica. RESULTADOS: 1) A prevalência de glaucoma nos pacientes com blefaroespasmo foi significativamente maior do que nos indivíduos do grupo controle, sendo diagnosticada em 14,3% e 3,6% dos casos, respectivamente (p=0,008). 2) A pressão intra-ocular foi significativamente maior nos pacientes com blefaroespasmo (15,80 ± 3,80 mmHg) do que nos indivíduos do grupo controle (13,90 ± 2,75 mmHg) (p= 0,004). 3) O pico da pressão intra-ocular na prova de sobrecarga hídrica foi significativamente maior nos pacientes com blefaroespasmo essencial (18,82 ± 4,47 mmHg) do que nos indivíduos do grupo controle (16,27 ± 2,69 mmHg) (p=0,0421). DISCUSSÃO: Diversos estudos descreveram a influência da compressão palpebral sobre a pressão intra-ocular. A prova de sobrecarga hídrica tem sido considerada uma ferramenta indireta para se avaliar a capacidade do fluxo de drenagem do trabeculado, além de exibir correlação com os picos de pressão intra-ocular que muitas vezes não são detectados em exames de rotina. Os pacientes com blefaroespasmo essencial apresentaram pressões intra -oculares e picos de pressão intra-ocular na prova de sobrecarga hídrica mais elevados do que os pacientes do grupo controle, o que poderia indicar um baixo fluxo de drenagem. Estas altíssimas variações de pressão intra -ocular a que estes indivíduos são submetidos constantemente, em pacientes com menor fluxo de drenagem poderiam causar um aumento crônico da pressão intra -ocular e o desenvolvimento do glaucoma. CONCLUSÕES: Os resultados observados sugerem que estes pacientes compõem um grupo de risco para o desenvolvimento de glaucoma e esta doença deve ser pesquisada de maneira sistemática na avaliação inicial e durante o seguimento desses casos / INTRODUCTION: Essential blepharospasm is a focal distonia characterised by involuntary, spasmodic, bilateral contractions of eyelid protractors. Glaucoma is the most important cause of irreversible blindness in adults in developed countries and high intraocular pressure is the major risk factor for development of the disease. Voluntary forced eyelid closure can produce an intraocular pressure increase of 90 mmHg. As patients with essential blepharospasm present frequent and strong eyelid contractions, they could be at risk for glaucoma development. METHODS: Twenty eight patients with essential blepharospasm and 28 patients of a control group, with eyelid diseases or in the post-operative period, were submitted to a complete ophthalmic examination. In the group of patiens with blepharospasm, the evaluation was done between 8 to 11 days after botulinum toxin treatment. We performed refractometry and best corrected visual acuity with Snellen chart, slitlamp biomicroscopy, applanation tonometry, automated perimetry, water drinking test and dilated funduscopy to evaluate optic discs. RESULTS: 1) Prevalence of glaucoma in patients with blepharospasm (14,3%) was higher than in the individuals from control group (3,6%) (p=0,008). 2) Intraocular pressure was higher in patients with blepharospasm (15,80 ± 3,80 mmHg) than in the individuals from control group (13,90 ± 2,75 mmHg) (p=0,004). 3) Intraocular pressure peaks in the water drinking test were higher in patients with essential blepharospasm (18,82 ± 4,47 mmHg) than in the individuals from control group (16,27 ± 2,69 mmHg) (p=0,0421). DISCUSSION: Several studies reported the influence of eyelid compression over intraocular pressure. The water drinking test has been considered as an indirect tool to measure outflow facility and it has good correlation with intraocular pressure peaks which are frequently missed in routine examinations. Patients with essential blepharospasm had higher mean intraocular pressures and intraocular pressure peaks in the water drinking test than patients from control group, which could indicate low outflow facility. These high intraocular pressure variations in patients with low outflow facility could increase the intraocular pressure chronically and lead to development of glaucoma. CONCLUSION: Our results suggest that patients with essential blepharospasm be at higher risks for development of glaucoma and this disease should be always investigated at presentation and during follow-up of these cases

A pressão intra-ocular (PO) é um importante parâmetro na avaliação da saúde ocular, sendo que o diagnóstico e a monitorização do glaucoma dependem de sua adequada mensuração. Entretanto estudos recentes mostram uma redução na PO medida através de tonômetros de aplanação após a cirurgia, o que provavelmente, é provocado por alterações da forma, estrutura e espessura da córnea em decorrência de procedimento cirúrgico freqüente no tratamento da miopia. A medida da PO é realizada aplicando uma pressão externa sobre o centro da córnea até que essa esteja totalmente plana. A deformação provocada pela pressão externa depende não somente da pressão intra-ocular mas também da energia de interação entre as moléculas da córnea, entre as moléculas do humor aquoso assim como, da interação mútua entre as moléculas do humor aquoso e da córnea. A quantidade e o tamanho das moléculas que formam estas estruturas (humor aquoso e córnea) também influenciam a deformação. Portanto, propomos neste trabalho, um modelo computacional que permite representar as moléculas da córnea e do humor aquoso com suas devidas espessuras e arranjos em função das energias de interação. O trabalho foi desenvolvido utilizando o programa DICE, o qual tem a finalidade de simular sistemas moleculares densos, compostos por diferentes tipos de partículas interagindo através de uma função (U) que descreve como a energia potencial de interação varia com a distância entre elas. Após diversas modificações dos parâmetros iniciais verificamos a tendência para o equilíbrio do sistema provando que o modelo é viável e factível de ser aplicado a avaliação da PO. / Intraocular pressure is an important parameter in the evaluation of eye health so that the diagnosing and monitoring of glaucoma depend on their correct measuring. However recent studies show a reduction in intraocular pressure measured by means of plaining tonometers after surgery, what is probably caused by alterations in the form, structure and thickness of the cornea as a result of the surgical procedure frequent in treatment of miopy. Intraoculoar pressure is measured by applying an external pressure on the center of the cornea until it is completely plain (flat). The deformation caused by external pressure depends not only on intraocular pressure but also on the interaction force among the molecules of the cornea, among the molecules of the aqueous humour and also on the mutual interaction among the molecules of the aqueous humour and those of the cornea. The quantity and size of the molecules that make up these structures (aqueous humour and cornea) have an influence on the deformation as well. So, we propose in this work a computational model that allows to represent the molecules of the cornea and aqueous humour with their respective thickness and arrangements in relation to the interaction forces. The work has been developed with the program DICE, whose objective is to simulate dense molecular systems, composed by different types of particles interacting by means of a function (U) that describes how the potential interaction force varies according to thedistance between them. After various modifications of the initial parameters we verified the tendency to the balance of the system, proving that the model is viable and feasible of being applied in evaluation of intraocular pressure.