O objetivo do presente estudo foi verificar os efeitos do treinamento intervalado de alta intensidade (TIAI), específico e não específico, sobre respostas fisiológicas e desempenho em testes aeróbios e anaeróbios, bem como sobre ações técnicas e táticas durante a luta de judô. 35 atletas de judô realizaram uma série de testes antes e após quatro semanas de treinamento, sendo aleatoriamente divididos em quatro grupos: TIAI para membros inferiores, TIAI para membros superiores, TIAI específico [por meio de entrada de golpes (uchi-komi)] e grupo controle. Os grupos experimentais treinaram o exercício intervalado de alta intensidade (EIAI) adicionalmente ao treino de judô e o grupo controle realizou apenas judô. Foi utilizado o mesmo tipo de estímulo em regiões corporais distintas: realização de duas sessões semanais de EIAI constituídas por dois blocos de 10 estímulos de 20s por 10s de intervalo entre os estímulos e 5 min entre os blocos, i.e., grupo de membros superiores e inferiores utilizaram cicloergômetros específicos para cada região corporal, enquanto o grupo específico desempenhou uchi-komi em intensidade all-out com atleta de massa corporal similar. Os grupos e momentos foram comparados via análise de variância (ANOVA) a dois fatores (grupo e momento do treinamento) ou a três fatores (grupo, momento do treinamento e momento da medida), seguida pelo teste de Bonferroni. Quando encontrada diferença entre os grupos durante as semanas de treinamento, foi efetuada uma ANOVA a um fator com medidas repetidas, bem como o teste-t pareado para os valores pré e pós-treinamento. Os principais resultados apontam que: para o grupo de membros inferiores houve aumento da potência equivalente ao onset blood lactate accumulation (OBLA) no teste progressivo para membros superiores, aumento da potência média no teste de Wingate adaptado para membros inferiores, redução da frequência cardíaca após o Special Judo Fitness Test (SJFT), redução do número de sequências em pé durante a simulação de luta e aumento da razão testosterona/cortisol (T/C) pós-simulação de luta no momento pós-treinamento; para o grupo de membros superiores, houve elevação da potência aeróbia máxima no teste progressivo máximo para membros superiores, aumento do número total de projeções no SJFT, redução das concentrações de CK e elevação da razão T/C pós-simulação de luta no pós-treinamento, bem como elevação das concentrações de LDH nas mensurações conduzidas em repouso; para o grupo uchi-komi, houve aumento da potência pico no teste de Wingate para membros superiores e inferiores, redução do índice no SJFT e aumento da razão T/C pós-simulação de luta no momento pós-treinamento. Não foram detectadas alterações no desempenho para o grupo controle pós-treinamento. Além disso, não foram detectadas quaisquer alterações para as respostas psicométricas, hormonais, assim como para o sistema nervoso autônomo após as quatro semanas de intervenção. Os resultados indicam que a adição do TIAI à rotina de treinamento usual de judô eleva a potência aeróbia máxima para membros superiores e desempenho intermitente de alta intensidade para membros superiores e inferiores em testes genéricos. Adicionalmente, o TIAI melhora aspectos relevantes para o desempenho em tarefas específicas do judô. Por fim, o TIAI de baixo volume não promoveu alterações nas respostas do sistema nervoso autônomo, questionários psicométricos e respostas hormonais ao longo das quatro semanas de treinamento / The aim of the present study was to verify the effects, specific and non-specific, of high intensity interval training (HIIT) on physiological and performance responses to aerobic and anaerobic tests, as well as on technical and tactical actions during judo combat. In order to achieve this purpose, 35 judo athletes were randomly selected into four groups: HIIT for lower-body, upper-body, specific group (by means of technique-entrance, uchi-komi) and a control group. These groups completed a series of tests, before and after a 4-week training period. The experimental groups did high intensity interval exercise (HIIE) in addition to judo training while the control group did judo training only. The same type of stimulus was used on distinct body regions: two weekly sessions of HIIE consisting of two blocks of 10 x 20s stimuli with a 10s interval between stimuli and a 5-min interval between blocks, i.e., the lower and upper-body group used cycle-ergometer for each body region, while the specific group carried out uchi-komi at all-out intensity with another athlete of similar body mass and stature. The groups and moments were compared via variance analysis (ANOVA) to two factors (group and training) or to three factors (group, training and time of measurement), followed by the Bonferroni test. When a difference was detected between groups during the training weeks, a one-way (ANOVA) was carried out with repeated measures, as well as the paired t-test, for pre and post-training values. The main results indicate that: The lower-body group showed increase in the equivalent power to onset blood lactate accumulation (OBLA), in aerobic fitness test for upper- limbs, increase in the mean power in the Wingate test (4 sets of 30s interspersed with 3-min recovery period) for lower limbs, heart rate reduction after the Special Judo Fitness Test (SJFT), reducing the number of standing sequences during the match simulation and increasing the testosterone/cortisol ratio (T/C) after the match simulation in the post-training period; For the upper-body group, showed an increase of the maximum aerobic power in aerobic fitness test for upper limbs, increase in the total number of projections in SJFT, reduced CK concentrations (post-training period), increase in T/C ratio post-match in the post-training period and increase in LDH concentrations in measurements conducted at rest. Uchi-komi group, showed an increased in the peak power in the Wingate test for upper and lower limbs, reduction of the SJFT index and increasing the T/C ratio after the match-simulations in the post-training period. As expected, were not found any performance changes after 4-weeks of intervention for the control group Furthermore, were not detected any changes to the psychometric, hormonal responses, as well as the autonomic nervous system after four weeks of intervention for all experimental groups. Therefore, these findings suggest that addition of the HIIT to usual judo training increases the maximum aerobic power for upper limbs and high-intensity intermittent performance for upper and lower limbs, in generic tests. Moreover, HIIT improves relevant aspects to performance in specific judo tasks. Finally, low volume HIIE did not bring about any alterations to the autonomous nervous system responses, psychometric responses or hormonal responses throughout the four weeks of training

Despite clear recommendations on the minimal amount of physical activity for achieving health benefits and reducing risk of chronic disease, the majority of people in the Western world remain sedentary. As a 'lack of time' has been identified as one of the main barriers to becoming and remaining physically active, in the past decade research has focused on high-intensity interval training (HIT) as a time-efficient alternative to aerobic exercise. Although initial studies convincingly demonstrated equal or better health benefits with various HIT protocols compared to much larger volumes of aerobic exercise, these HIT protocols tend to be very strenuous and as such are unlikely to be adhered to by sedentary populations. Furthermore, most HIT protocols are not as time-efficient as sometimes claimed, with the total time per exercise session generally exceeding 20-30 minutes. This thesis aimed to characterise the effects of a novel reduced-exertion HIT (ReHIT) protocol, requiring a maximum of 2 x 20 s all-out sprint efforts in a 10 min training session, upon insulin sensitivity, aerobic capacity, glycogen utilisation and associated acute metabolic responses. The ReHIT exercise bouts were well tolerated by participants, but were associated with a substantial disturbance of physiological homeostasis including muscle glycogen degradation, lactate accumulation, excursions in plasma volume, post-exercise oxygen consumption, respiratory exchange ratio and heart rate, as well as a skeletal muscle signalling response through AMPK, and increases in skeletal muscle GLUT4 and PGC1α mRNA expression (Chapter 4 and 5). The combined training studies (n=49) provide some support for improvements in key disease biomarkers following ReHIT, with improvements in insulin sensitivity observed in men, and increased aerobic capacity observed in men and women (Chapter 7). These observations highlight a potential regulatory role for glycogen in exercise-induced adaptation. However, the mean improvements in insulin sensitivity in men were not consistent between the two training studies (Chapter 2 and 6), and there was a high level of variability observed between individuals (Chapter 6 and 7). Therefore, the impact of ReHIT on insulin sensitivity needs to be further explored in the context of a randomised controlled trial, and the mechanisms underpinning the large variability in adaptive response need to be characterised.

Ettlia oleoabundans, a freshwater green microalga, was grown under different environmental conditions to study its growth, lipid yield and quality for a better understanding of the fundamental physiology of this oleaginous species. E. oleoabundans showed steady increase in biomass under low temperature and low light intensity, and at high temperature lipid cell content significantly increased independent of nitrate depletion. Studies on light quality showed that red light treatment did not change the biomass concentration, but stimulated lipid yield especially oleic acid, the most desirable biodiesel precursor. Moreover, no photoreversibility in lipid production was observed when applying alternating short-term red and far-red lights, which left the phytochrome effect still an open question. In addition, carbon dioxide enrichment via an air sparging system significantly boosted exponential growth and increased carbon conversion efficiency. Finally, a practical study demonstrated the feasibility of growing E. oleoabundans for high lipid production using a diluted agricultural anaerobic waste effluent as the medium. Together, these studies showed the potential of E. oleoabundans as a promising high yield feedstock for the production of high quality biodiesel.

Submitted by Maicon Juliano Schmidt (maicons) on 2015-03-21T13:26:33Z No. of bitstreams: 1 Fabio Nascimento.pdf: 1223575 bytes, checksum: e029bdb61fc32333b6784283ac687984 (MD5) / Made available in DSpace on 2015-03-21T13:26:33Z (GMT). No. of bitstreams: 1 Fabio Nascimento.pdf: 1223575 bytes, checksum: e029bdb61fc32333b6784283ac687984 (MD5) Previous issue date: 2013-01-30 / Nenhuma / O propósito central deste estudo é verificar se houve reprimarização da pauta exportadora brasileira para os países componentes dos BRICS no período de 2000 a 2011. Para isto são utilizados dados de comércio internacional relacionados às pautas exportadoras dos países BRICS, agrupados por SH6, fornecidos pela base de dados Aliceweb, que totalizam 1547 produtos agrupados de acordo com sua intensidade tecnológica em: produtos primários, intensivos em recursos naturais, intensivos em trabalho, intensivos em economias de escala, fornecedores especializados e intensivos em pesquisa e desenvolvimento. É realizada também a análise dos dados das pautas exportadoras dos países BRICS com direção ao BRICS afim verificar se a pauta exportadora brasileira segue a tendência do agrupamento. São estudados ainda temas como a evolução dos BRICS sob a ótica da agência internacional Goldman Sachs e como se deu sua formação, além de, observar-se alguns estudos que tratam dos temas pertinentes ao trabalho como as teorias sobre intensidade tecnológica, reprimarização e seus reflexos na economia e desenvolvimento de uma nação. Todos os resultados apontam que houve reprimarização da pauta exportadora brasileira no período em questão, assim como em todos os países BRICS, com exceção a China. / The central purpose of this study is verify if had reprimarization of Brazilian export agenda to componentes of BRICS countries in the period of 2000 to 2011. Are used for this international trade data relating the export agendas of BRICS countries, grouped by SH6, provided by the Aliceweb database, totaling 1547 products grouped according to their technological intensity in: primary products, natural resources intensity, work intensity, economy scale intensity, suppliers specialized and research and development intensity. Is also carried out the analysis of export agenda data of BRICS countries with direction to BRICS in order to verify if the Brazilian export agenda follow the tendency of the grouping. Are still studied topics such as the evolution of BRICS over the optic of international agency Goldman Sachs and how was its formation, in addition to, observed some studies dealing with relevant issues to the work as theories of technological intensity, reprimarization and its reflexes on the economy and development of a nation. All the results show that was reprimarization of Brazilian export agenda in the period concerned, as well as all BRICS countries, with exception China.

Submitted by Vanessa Nunes (vnunes) on 2015-07-28T18:51:01Z No. of bitstreams: 1 Rosangela Viegas Maraschin.pdf: 451907 bytes, checksum: 877d6fb769dfa6d857f746ebbea8a50a (MD5) / Made available in DSpace on 2015-07-28T18:51:01Z (GMT). No. of bitstreams: 1 Rosangela Viegas Maraschin.pdf: 451907 bytes, checksum: 877d6fb769dfa6d857f746ebbea8a50a (MD5) Previous issue date: 2015-04-30 / Nenhuma / O objetivo do estudo foi analisar o perfil da pauta exportadora do Brasil para o Mercosul, por intensidade tecnológica, no período 2000-2014. A metodologia empregada foi a revisão bibliográfica e a base de dados utilizada foi o AliceWeb (MDIC). A identificação das categorias de intensidade tecnológica seguiu a classificação de Pavitt (1984). Os resultados revelaram um perfil semelhante entre as pautas de exportação do Brasil para o mundo e para o Mercosul no que se refere à expansão do comércio de produtos primários, evidenciando o processo de reprimarização. No entanto, ressalta-se a dominância dos produtos intensivos em economia de escala no comércio entre o Brasil e o bloco sul-americano. / The purpose this paper to analyze Brazil export profile to Mercosur, by technological intensity, within the period of 2000 to 2014. The methodology employed was the literature review and the data base applied was the AliceWeb (MDIC). The technological intensity categories identification followed the Pavitt’s classification (1984). The results showed an equivalent profile between Brazil’s export line to the world and to the Mercosur in relation to primary products commerce expansion, highlighting the reprimarization process. At the same time, it emphasizes the dominance of intensive products in scale economy between Brazil and the South American Bloc.

The ability to extract accurately the stress intensity factor and the T-Stress for fractured engineering materials is very significant in the decision-making process for in-service engineering components, mainly for their functionality and operating limit. The subject of computational fracture mechanics in engineering make this possible without resulting to expensive experimental processes. In this thesis, the Finite Block Method (FBM) has been developed for the meshless study of interface stationary crack under both static and dynamic loading in bi-materials. The finite block method based on the Lagrangian interpolation is introduced and the various mathematical constructs are examined. This includes the use of the mapping technique. In a one-dimensional and a two-dimensional case, numerical studies were performed in order to determine the interpolation error. The finite block method in both the Cartesian coordinate and the polar coordinate systems is developed to evaluate the stress intensity factors and the T-stress for interface cracks between bi-materials. Using the William's series for bi-material, an expression for approximating the stress and displacement at the interface crack tip is established. In order to capture accurately the stress intensity factors and the T-stress at the crack tip, the asymptotic expansions of the stress and displacement around the crack tip are introduced with a singular core technique. The accuracy and capability of the finite block method in evaluating interface cracks is demonstrated by several numerical assessments. In all cases, comparisons have been made with numerical solutions by using the boundary collocation method, the finite element method and the boundary element method, etc.

Introdução: O sobrepeso e a obesidade representam um grave problema de Saúde Pública, tendo seu desenvolvimento associado à adolescência, impacto negativo na fase adulta, sobretudo, devido suas complicações metabólicas. Considerando que o caráter crônico e inflamatório de baixa intensidade presente na obesidade estimula a geração de radicais livres, torna-se relevante avaliar a relação entre as adipocitocinas e a oxidação das lipoproteínas. Objetivos: Avaliar a possível influência da obesidade sobre a LDL(-) e adipocitocinas. Material e Métodos: Foram recrutados 156 adolescentes de ambos os sexos, com faixa etária de 10 a 19 anos e regularmente matriculados em escolas públicas da cidade de São Paulo. Os adolescentes foram distribuídos em três grupos: Eutrófico, Sobrepeso e Obeso, segundo COLE et al. (2000). Após jejum (12-15h) foi coletada uma amostra de sangue e a partir do plasma realizamos as seguintes análises: perfil lipídico, glicose e insulina (kits comerciais), LDL(-) e seus auto-anticorpos (ELISA), leptina, resistina e adiponectina (ELISA). O perfil sócio-econômico e clínico dos adolescentes foi investigado por meio de questionários estruturados. Foram coletadas informações antropométricas (peso, altura, circunferência da cintura, porcentagem de gordura) e dados de consumo alimentar (3 x R24h). O consumo alimentar foi estimado por meio do programa NutWin®. As diferenças entre as variáveis qualitativas foram determinadas pelo teste c2. As variáveis quantitativas foram ajustadas pela idade por meio do General Linear Model, sendo as diferenças entre os grupos estabelecidas pelo teste post-hoc de Bonferroni (SPSS®, versão 15.0). Resultados: Dos 156 adolescentes incluídos no estudo, 76 (48,7 por cento ) foram meninos e 80 (51,3 por cento ) meninas, com idade média de 14,5 ± 2,3 anos. Os adolescentes foram distribuídos em três grupos: Eutrófico (n = 52 adolescentes; 33,3 por cento ), Sobrepeso (n = 53 adolescentes; 34,0 por cento ) e Obeso (n = 51 adolescentes; 32,7 por cento ). Estes grupos foram pareados quanto ao sexo, escolaridade da mãe, renda, maturação sexual e antecedentes familiares de doenças. Como previsto pelo critério de estratificação dos grupos, os valores médios de IMC foram diferentes entre os grupos, sendo confirmados pela CC e porcentagem de gordura. Em relação ao hábito alimentar, a análise dos dados brutos e ajustados pela energia e variabilidade intrapessoal não apresentou diferença entre 4 os grupos. As análises da glicemia de jejum, colesterol total, triacilgliceróis e LDL-C não apresentaram diferenças entre os grupos. A insulina plasmática no grupo Obeso apresentou valores superiores aos grupos Eutrófico (p< 0,001) e Sobrepeso (p< 0,001), e o índice HOMA-IR no grupo Obeso apresentou valores superiores aos grupos Eutrófico (p< 0,001) e Sobrepeso (p< 0,001), enquanto o HDL-C apresentou valores maiores no grupo Eutrófico, quando comparado ao Obeso (p=0,012). A LDL(-) e seus autoanticorpos apresentaram diferentes concentrações entre os grupos (p= 0,040; p= 0,026, respectivamente). A leptina no grupo Eutrófico apresentou valores menores que os grupos Sobrepeso (p< 0,001) e Obeso (p< 0,001), assim como o grupo Sobrepeso apresentou valores inferiores ao grupo Obeso (p< 0,001). Perfil inverso foi observado em relação à concentração de adiponectina, A resistina apresentou valores maiores no grupo Obeso (p= 0,006), que no grupo Eutrófico. A leptina apresentou correlações positivas com percentual de gordura (r= 0,540; p= 0,001), circunferência da cintura (r= 0,679; p= 0,003) e IMC (r= 0,670; p< 0,001). Em relação ao metabolismo de carboidratos, a leptina se correlacionou positivamente com a insulina (r= 0,578; p< 0,001) e o HOMA-IR (r= 0,570; p= 0,001), enquanto a adiponectina se correlacionou negativamente com insulina (r= -0,255; p= 0,001) e o HOMA-IR (r= -0,246; p=0,002). Em relação ao perfil lipídico, a leptina correlacionou-se com colesterol total (r= 0,496; p= 0,003), triacilgliceróis (r= 0,409; p= 0,016) e LDL-C (r= 0,416; p= 0,014), assim como a adiponectina correlacionou-se com LDL(-) (r= -0,428; p= 0,012) e a resistina com HDL-C (r= -0,337; p= 0,050). Portanto, os resultados obtidos demonstram que adolescentes com excesso de peso, mesmo ainda considerados clinicamente saudáveis, apresentam diversos parâmetros antropométricos e bioquímicos alterados, que sugerem a presença de um elevado número de fatores de risco cardiometabólico nessa população / Introduction: Overweight and obesity represent a serious Public Health issue. Their development associated with adolescence, generate a negative impact in adulthood, mainly because of metabolic complications. As the low and chronic inflammatory state present in obesity stimulates the generation of free radicals, it becomes relevant to assess the relationship between adipocytokines and the oxidation of lipoproteins. Objective: Evaluate the possible influence of overweight and obesity on the electronegative LDL and adipocytokines (leptin, adiponectin and resistin). Materials and Methods: Adolescents of both genders, aged 10 to 19 years old and regularly registered in public schools at the city of São Paulo were recruited for this research. They were divided into three groups: Healthy weight, Overweight and Obese, according to Cole et al. (2000), by gender and age. After fasting (12-15h) a blood sample was collected and the following tests were performed on each samples plasma: total lipid profile, glucose and insulin (commercial kits), leptin, resistin, adiponectin (ELISA), LDL(-) (ELISA) and its autoantibodies (ELISA). The socio-economic and health profiles of the adolescents were determined by structured questionnaires. Anthropometric (weight, height, waist circumference - WC, percentage of body fat) and food consumption data (3 x 24-hour recall) were collected. The 24-hour recall data was analyzed by the NutWin® software. Differences between qualitative variables were determined by c2 test. Quantitative variables were adjusted for age by means of General Linear Model, being the differences between the groups established by post-hoc Bonferroni test (SPSS ®, version 15.0). Results: Of the 156 eligible individuals, 76 (48.7 per cent ) were boys and 80 (51.3 per cent ) girls, with the average age being of 14.5 ± 2.3 years. The adolescents were divided into three groups: Healthy weight, n = 52 adolescents (33.3 per cent ), Overweight, n = 53 adolescents (34.0 per cent ) and Obese, n = 51 adolescents (32.7 per cent ). These groups were matched up by gender, mother\'s education, income, sexual maturation, and current medical history. As expected by the group inclusion criteria, there were statistical differences in BMI and this profile was confirmed by WC and body fat. Opposite profile was showed for lean body mass. In relation to food consumption, the analysis of crude data adjusted for energy and intrapersonal variability did 6 not differ between the groups. Analyses of fasting glucose, total cholesterol, triglycerides and LDL-C did not differ between the groups. There were higher levels of plasma insulin and HOMA-IR in the obese group than in the healthy weight (p <0.001; p <0.001) and the overweight (p <0.001; p < 0.001) groups. HDL-C in the healthy weight group showed increased values in comparison to Obese one (p = 0.012). The LDL (-) in plasma and its autoantibodies indicated different concentrations between the groups (p = 0.040, p= 0.026, respectively). There were lower values of leptin both in the healthy weight group in comparison with the overweight (p <0.001) and the obese (p <0.001) groups, as well as in the Overweight group in comparison with the Obese group (p <0.001). Opposite profile was observed for adiponectin levels, between the healthy weight group and the overweight (p = 0.019) and obese (p = 0.000) groups. Resistin showed higher values in the obese group (p = 0.006) than in the healthy weight group. Leptin showed positive correlations with body fat percentage (r= 0.540 and p= 0.001), waist circumference (r= 0.679 and p= 0.003) and BMI (r= 0.670 and p <0.001). In relation to carbohydrate metabolism, leptin correlated positively with insulin (r= 0.578 and p <0.001) and HOMA-IR (r= 0.570 and p= 0.001), and opposite profile was showed for adiponectin (Insulin: r= -0.255, p= 0.001; HOMA-IR: r= -0.246, p= 0.002, respectively). Regarding the lipid profile, leptin correlated with total cholesterol (r= 0.496 and p= 0.003), triglycerides (r= 0.409 and p= 0.016) and LDL-C (r= 0.416 and p= 0.014); adiponectin correlated with LDL (-) (r= -0.428, p= 0.012); and resistin with HDL-C (r= -0.337, p= 0.050). Therefore, the results show that overweight and obese adolescents, even those who are still considered clinically healthy, showed several anthropometric and biochemical changes, which suggest increased number of cardiometabolic risk factors in this population

INTRODUÇÃO: A combinação de radioterapia e altas doses de cisplatina no tratamento do meduloblastoma tem se mostrado causa de importante ototoxicidade. Com a introdução da técnica de intensidade modulada do feixe (IMRT), tornou-se possível diminuir a dose média de radiação no aparelho auditivo. OBJETIVOS: O objetivo é determinar se com a radioterapia com reforço de dose com IMRT, é possível atingir índices menores de perda auditiva e se há um limite de dose no ouvido para a mesma. Analisar também se o volume de ouvido contornado durante o planejamento inverso influencia o resultado. MÉTODO: Quarenta e um pacientes com meduloblastoma (idade mediana, 10 anos) com audição normal ao início da radioterapia com IMRT foram avaliados retrospectivamente. O último seguimento e a última audiometria realizada após o término da radioterapia foram considerados. A função auditiva foi graduada em uma escala de 0 a 4 de acordo com os critérios de toxicidade do Pediatric Oncology Group (POG). As doses mínima, máxima, média e mediana recebidas pelo aparelho auditivo, bem como o volume contornado no planejamento do IMRT foram correlacionados com o grau de função auditiva. Foi realizada análise univariada e multivariada dos dados. RESULTADOS: O seguimento mediano foi de 41 meses (12,8 a 71) para avaliação audiométrica e 44 meses (14-72) para a sobrevida global. As doses medianas mínima, máxima, média e mediana recebidas pelo aparelho auditivo foram respectivamente de: 3785 (589,4 a 4758,2), 4832,5 (3724 a 5447,9), 4366,5 (2808,5 a 5097,3) e 4360,5 (2878 a 5031,1). Sete pacientes (17%) apresentaram perda auditiva graus 3 e 4. A análise univariada entre as variáveis não mostrou diferença com significância estatística, exceto para a dose de cisplatina (P < 0,03). Na análise multivariada com regressão logística, a dose mediana no aparelho auditivo foi um fator significativo para a perda auditiva graus 3 e 4 (P < 0,01), ao passo que a dose cumulativa de cisplatina apresentou tendência à perda graus 3 e 4 (P = 0,075). Não houve correlação entre o volume contornado no planejamento a perda auditiva. Perda auditiva graus 3 e 4 foi incomum com dose mediana no aparelho auditivo menor que 42 Gy (P = 0,063) e dose cumulativa de cisplatina abaixo de 375 mg/m² (P < 0,01). Nenhum paciente que recebeu carboplatina em substituição à cisplatina apresentou perda auditiva grave. Não houve associação, com significância estatística, entre as variáveis analisadas e a ototoxicidade, quando estes pacientes foram excluídos da análise. Quatro pacientes morreram e dois apresentaram recidiva no momento do estudo, levando a uma sobrevida global de 90% e uma sobrevida livre de doença de 85% em 44 meses. CONCLUSÕES: Os resultados mostram que o tratamento com IMRT leva a uma baixa taxa de perda auditiva grave, mesmo com um seguimento maior, o que é consistente com outros estudos. Acreditamos ser seguro contornar somente a cóclea e que uma dose mediana para a mesma deve ser mantida abaixo de 42 Gy. A quimioterapia com cisplatina continua a ter um papel importante no tratamento, no entanto a dose cumulativa não deve exceder 375 mg/m². A sobrevida foi impressionante neste estudo, uma vez que 21 (51,2%) foram classificados como alto risco / INTRODUCTION: The combination of radiation therapy and cisplatin chemotherapy for the treatment of medulloblastoma is a known cause of important ototoxicity. With the introduction of intensity-modulated radiation therapy (IMRT), it became possible to deliver less radiation to the auditory apparatus. PURPOSE: To determine if boost radiotherapy with IMRT can achieve a lower rate of hearing loss and if theres a cutoff dose for it. Also, to analyze whether the auditory apparatus volume contoured in inverse planning influences the outcome. METHODS: Forty-one pediatric medulloblastoma patients (median age, 10 years) with normal hearing at the time of radiation with IMRT were retrospectively evaluated. The last audiogram and follow-up from the completion of radiation were considered. Hearing function was graded on a scale 0 to 4 according to Pediatric Oncology groups toxicity criteria. Minimum, maximum, mean and median doses to the inner ear and its volume contoured in IMRT planning, as well the cisplatin dose were recorded and correlated with hearing function. Univariate and multivariate data analysis were performed. RESULTS: The median follow-up was 41 months (range 12.8-71.0 months) for audiometric evaluation and 44 months (range 14-72 months) for survival. Median doses for minimum, maximum, mean and median in the inner ear were respectively: 3785 (range, 589.4 to 4758.2), 4832.5 (range 3724 to 5447.9), 4366.5 (range 2808.5 to 5097,3) and 4360,5 (range 2878 to 5031,1). Seven patients (17%) have experienced Grade 3 or 4 hearing loss. Univariate analysis showed no difference among the variables with statistical significance, except for cisplatin dose (P < 0.03). In multivariate analysis with logistic regression, median dose in inner ear was a significant factor for hearing loss grade 3 or 4 (P < 0,01), meanwhile cisplatin dose had a trend to hearing loss grade 3 or 4 (P = 0.075). There was no relationship between the auditory apparatus volume contoured in planning and hearing loss. Grade 3 or 4 hearing loss were uncommon with median dose to the inner ear bellow 42 Gy (P = 0.063) and cisplatin dose less than 375 mg/m² (P < 0.01). None of the patients who received carboplatin in lieu of cisplatin had severe hearing loss. There was no statistically significant association between ototoxicity and the variables, when these patients were excluded from the analysis. Four patients died and two have recurred at the time of the study with a 90% overall survival rate and 85% disease free survival in 44 months. CONCLUSIONS: Our findings shows that IMRT treatment leads to a low rate of serious hearing loss even with a longer follow-up, which is consistent with others trials. We believe that is safe to contour only the cochlea and that a median dose to it should be kept below 42Gy. Cisplatin chemotherapy continues to have an important role in treatment, however doses should not exceed 375 mg/m². Survival rates were impressing in this trial given the fact that 21 (51.2%) patients were classified as high risk

Philosophiae Doctor - PhD (Physiotherapy) / Stroke is a debilitating medical and neurological condition. It is the leading cause of adult disability worldwide. Disability from stroke covers the three key classifications of the WHO-ICF framework on human function centred on health and health related issues, implying that the disability in stroke involve structural and activity limitations to participation restriction. Rehabilitation remains the hallmark of managing the plethora of neurological deficits accompanying stroke. Currently, the key advocacy in neuroscientific studies for stroke rehabilitation is that therapy should be directed towards task specificity. Task Specific Training most recently, the form of Circuit Class Therapy and the intensity of multiple repetition of the task has been identified as physiological mechanisms behind sustained motor learning following stroke.Circuit Class Therapy (CCT) is a form of Task Specific Training (TST) that involves the practice of structuring tasks in a circuit or series of workstations. It offers the patient the ability to practice multiple tasks in a conducive environmental because of its three key features of utilisation of different workstations that allow people to practice intensively in a meaningful and progressive way to suit their respective needs; the efficient utilisation of therapists'/trainees' time; and the group dynamics such as peer support and social support. Although these features are attainable following CCT challenges remain in selecting the most efficient intensity that could produce these benefits in stroke survivors. This study investigated the effectiveness of differing intensities of CCT in the rehabilitation of stroke survivors using the ICF framework to guide patients� response assessments after training.

The blood-brain barrier (BBB) is physiologically essential for brain homeostasis. While it protects the brain from noxious agents, it prevents almost all currently available drugs from crossing to the parenchyma. This greatly hinders drug delivery for the treatment of neurological diseases and disorders such as Parkinson’s, Alzheimer’s and Huntington’s, as well as the development of drugs for the treatment of such diseases. Current drug delivery techniques to the brain are either invasive and target specific, or non-invasive with low special specificity. Neither group of techniques are optimal for long term treatment of patients with neurological diseases or disorders. Focused ultrasound coupled with intravenous administration of microbubbles (FUS) has been proven as an effective technique to selectively and noninvasively open the BBB in multiple in vivo models including non-human primates (NHP). Although this technique has promising potential for clinical outpatient procedures, as well as a powerful tool in the lab, the safety and potential neurological effects of this technique need to be further investigated. This thesis focuses on validating the safety and efficacy of using the FUS technique to open the BBB in NHP as well as the ability of the technique to facility drug delivery. First, a longitudinal study of repeatedly applying the FUS technique targeting the basal ganglia region in four NHP was conducted to determine any potential long-term adverse side effects over a duration of 4-20 months. The safety of the technique was evaluated using both MRI as well as behavioral testing. Results demonstrated that repeated application of the FUS technique to the basal ganglia in NHP did not generate permanent side effects, nor did it induce a permanent opening of the BBB in the targeted region. The second study investigated the potential of the FUS technique as a method to deliver drugs, such as a low dose of haloperidol, to the basal ganglia in NHP and mice to elicit pharmacodynamical effects on responses to behavioral tasks. After opening the BBB in the basal ganglia of mice and NHP, a low dose of haloperidol was successfully delivered generating significant changes in their baseline motor responses to behavioral tasks. Domperidone was also successfully delivered to the caudate of NHP after opening the BBB and induced transient hemilateral neglect. In the final section of this thesis, the safety and efficacy of the FUS technique was evaluated in fully alert NHP. The FUS technique was successful in generating BBB opening volumes larger on average to that of the BBB opening volumes in anesthetized experiments. Safety results through MRI verification as well as behavioral testing during application of the technique demonstrated that the FUS technique did not generate adverse neurological effects. Conversely, the FUS technique was found to induce slight positive effects on the response of the NHP to the behavioral task. Collectively, the work presented in this thesis demonstrates the safety and effectiveness of the FUS technique to open the BBB and deliver neuroactive drugs in the NHP.