Orientador: Marcelo Augusto Assunção Sanches / Resumo: Neste trabalho é apresentado o desenvolvimento de um sistema de alinhamento referenciado de prótese de membro inferior, denominado PASyLL (Prosthesis Alignment System of Lower Limbs). A qualidade do alinhamento e ajuste de próteses de membros inferiores é fundamental no processo de reabilitação, principalmente porque contribui para que não ocorra o abandono do uso da prótese. Atualmente, muitos alinhamentos de próteses ainda são realizados de forma subjetiva, sem auxílio de equipamentos, ou seja, apenas com base na experiência e conhecimento do profissional de saúde. Diante disso, desenvolveu-se o PASyLL, um sistema para auxiliar o profissional da saúde no alinhamento de prótese. Este equipamento mede parâmetros importantes para um alinhamento adequado, fornece ao terapeuta dados objetivos, auxiliando-o na tomada de decisão. Com este sistema é possível medir e realizar ajustes no comprimento, medir a distribuição do peso no membro protetizado e não protetizado, verificar a posição do centro de pressão do paciente (COP), desta forma auxiliar no ajuste médio lateral e anteroposterior. O sistema possui fachos laser na horizontal e vertical, permitindo assim um alinhamento referenciado. O erro percentual na medição do peso foi inferior a 1% e na medida do COP, inferior a 5%. / Abstract: In this work the development of a referenced alignment system of lower limb prosthesis, called PASyLL (Prosthesis Alignment System of Lower Limbs), is presented. The quality of the alignment and adjustment of lower limb prostheies is fundamental in the rehabilitation process, mainly because it contributes to the abandonment of prosthesis use. Currently, many prosthesis alignments are still performed subjectively, without the aid of equipment, that is, only based on the experience and knowledge of the health professional. Therefore, the PASyLL, a system to assist the health professional in the prosthesis alignment, was developed. This equipment measures important parameters for proper alignment, provides the therapist with objective data, assisting him in decision making. With this system it is possible to measure and adjust the length, measure the weight distribution in the amputated and not amputated limb, verify the position of the patient pressure center (COP) in this way assist in the lateral lateral and anteroposterior adjustment. The system has horizontal and vertical laser beams, allowing a referenced alignment. The percentage error in weight measurement was less than 1% and in the COP, less than 5%. / Mestre

O desenvolvimento embrionário dos membros é um processo complexo e dinâmico. É controlado por diversos genes e diversos mecanismos morfogenéticos, muitos dos quais ainda não estão completamente elucidados. O objetivo deste estudo é identificar as alterações genéticas responsáveis por defeitos de membros em quatro famílias brasileiras. A família 1 apresenta três indivíduos com um espectro extremamente variável de displasia ectodérmica, ectrodactilia e fenda labiopalatina, características da síndrome EEC. O gene TP63 foi analisado por sequenciamento de Sanger e foi descoberta uma variante nunca descrita anteriormente, c.1037C>A (p.Ala346Gly), em heterozigose, segregando com o fenótipo. Mutações no gene TP63 já foram associadas com casos da síndrome EEC. Concluímos que a variante no gene TP63 é a responsável pelo quadro clínico de EEC na família. A família 2 incluiu cinco indivíduos afetados por polegar trifalângico. O fenótipo de um dos indivíduos é mais grave e se caracteriza por, além do polegar trifalângico, pela presença de braço direito grosseiramente curto e deformado com dedos hipoplásicos, pé direito malformado com metatarsos hipoplásicos e orelha direita pequena e protuberante. Estudos de mapeamento gênico com arrays de SNPs revelaram Lod scores sugestivos de ligação com 8 regiões cromossômicas distintas. O sequenciamento massivo em paralelo do exoma com a amostra de um dos afetados, seguida da seleção das variantes presentes nas regiões com Lod scores sugestivos, revelou a presença da variante c.410dupG (p.Gly138Argfs∗43) no gene SALL4, a qual nunca havia sido descrita. Mutações no SALL4 que alteram a matriz de leitura já foram associadas com casos da síndrome de Okihiro, a qual é caracterizada por defeitos radiais de membros e anomalia oftalmológica de Duane. A segregação da variante entre os indivíduos afetados foi confirmada por sequenciamento de Sanger. Concluimos que esta variante é responsável pelo quadro clínico da família, a qual apresenta a síndrome de Okihiro, porém sem a anomalia de Duane. A análise de todos os casos descritos com variantes no gene SALL4 sugere que há uma correlação entre defeitos nos membros inferiores e o tamanho reduzido da proteína truncada SALL4. A família 3 apresenta três indivíduos afetados por sindactilia completa com polidactilia pré-axial nas mãos, classificada como sindactilia do tipo IV. O sequenciamento massivo em paralelo do exoma com as amostras de três indivíduos afetados e dois normais não revelou a presença de qualquer alteração genética candidata a explicar o quadro clínico. O estudo do array-CGH revelou uma duplicação de aproximadamente 97 kb no gene LMBR1 abrangendo a região de enhancer (ZRS) do gene SHH. Duplicações no ZRS já foram identificadas em casos de sindactilia do tipo IV. Concluímos que a duplicação no ZRS é responsável pelo quadro. A revisão da literatura sobre os casos com duplicação dessa região sugere uma correlação entre duplicações com tamanho ao redor de 97 kb e o fenótipo clássico de sindactilia do tipo IV. A família 4 apresenta seis indivíduos afetados por uma síndrome relativamente nova descrita por nossa equipe em 2008, a síndrome de Santos. Essa síndrome é caracterizada por aplasia/hipoplasia fibular e anoniquia/hipoplasia ungueal dentre outros defeitos de membros. O estudo de ligação com array de SNP e marcadores de microssatélites, com posterior cálculo de Lod score, indicou duas regiões no cromossomo 3 como candidatas a conter a alteração genética responsável pelo fenótipo. Análise dos genes presentes nessas regiões indicou o gene WNT7A como o principal candidato. Alterações neste gene já foram associadas com a síndrome de Fuhrmann e a AARRS (Al-Awadi⁄Raas-Rothschild syndrome), de herança recessiva, as quais apresentam fenótipos correlatos aos presentes na síndrome de Santos. O sequenciamento de Sanger deste gene revelou a presença da variante c.934G>A (p.Gly312Ser), não descrita, em homozigose em cinco dos seis indivíduos afetados da família. O sexto indivíduo afetado é heterozigoto e apresenta fenótipo muito menos grave. Não apresenta qualquer defeito fibular e ungueal, característicos da síndrome. Esse é o primeiro relato de um caso de defeitos de membros como resultado da presença de uma variante em heterozigose no gene WNT7A. O sequenciamento massivo em paralelo do exoma foi realizado com as amostras deste indivíduo e de um dos indivíduos afetados. Contudo, nenhuma outra variante se mostrou candidata a explicar o quadro clínico. Concluímos que a síndrome de Santos é o resultado desta mutação no gene WNT7A. Estudos funcionais in situ baseados na atividade da Luciferase estão em andamento para comprovar o efeito deletério desta variante / Limb development is a complex and dynamic process driven by many different genes and morphogenetic mechanisms. Many of them have not been properly clarified yet. The aim of this study is to identify genetic alterations responsible for limb defects in four Brazilian families. Family 1 includes three individuals affected by an extremely variable phenotype of ectrodactyly, ectodermal dysplasia and cleft lip/palate, and other clinical signs of EEC syndrome. The TP63 gene, associated with this condition, was analyzed through Sanger sequencing and a novel variant, c.1037C>A (p.Ala346Gly), was found; the variant segregated in heterozygous state with the EEC phenotype. Mutations in TP63 gene are already known to be associated with EEC syndrome. Due to the extremely variable phenotype presented by the individuals in the family, the possibility of the mutation c.1037C>G being related to acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome and SHFM cannot be ruled out. Family 2 presents five individuals affected by preaxial polydactyly (triphalangeal thumbs). The phenotype of the proband is more severe, being characterized by triphalangeal thumb, with the following manifestations: grossly shortened and deformed forearm, markedly hypoplastic and appendicular thumb and malformed right foot with hypoplastic metatarsals. Linkage studies by SNP-array pointed to suggestive Lod score values in 8 distinct chromosomal regions. Whole exome sequencing with the sample from one affected individual revealed a novel frameshift variant, c.410dupG (p.Gly138Argfs∗43) in the SALL4 gene. Frameshift mutations in the SALL4 were already associated to Okihiro syndrome, which is characterized by radial limb defects and Duane anomaly. The segregation of the variant among the affected individuals was confirmed by Sanger sequencing. We concluded that this variant is the cause of the clinical signs in the family, which was classified as presenting Okihiro syndrome without Duane anomaly. The review of all clinical cases reported with SALL4 variants indicates a possible correlation between the foot malformation and the reduced size of the SALL4 protein. Family 3 has affected individuals with complete hand syndactyly associated to pre-axial polydactyly (syndactyly type IV). Whole exome sequencing was performed with the samples collected from the three affected individuals and two non-affected ones and no pathogenic variant was detected in genes related to limb development segregating with the phenotype. Through array-CGH, nevertheless, a duplication of about 97 kb including the enhancer (ZRS) of the SHH gene was detected. Duplications in ZRS region were already reported in Syndactyly type IV. We concluded that the 97-kb duplication is the cause of the syndactyly type IV in the family. A review of reported cases (including ours) suggested a possible correlation between the duplication with 97 kb size and the classic phenotype of syndactyly type IV. Family 4 has six individuals affected by a new syndrome (Santos syndrome) described by members of our group in 2008, a condition characterized by fibular agenesis/hipoplasia and ungual hypoplasia⁄anonychia, among other limb defects. Linkage study by SNP-array and microsatellite markers was performed and Lod score calculation pointed to two candidate regions on chromosome 3. Search for candidate genes revealed the WNT7A as the best candidate. Mutations in WNT7A gene, in homozygous state, are known to cause two other limb defect syndromes, Fuhrmann syndrome and AARRS (Al-Awadi/Raas-Rothschild syndrome), both presenting similar phenotypes to Santos syndrome. Sanger sequencing showed a novel variant, in homozygous state, c.934G>A (p.Gly312Ser) in the WNT7A gene in five out of six affected individuals. One affected individual, much less severely affected than his relatives, carries the mutation in heterozygous state. He does not present fibular or ungual malformations, characteristic signals of the syndrome; instead, he is the carrier of a complex polydactyly in his left hand. This is the first report about a heterozygous variant in WNT7A gene resulting in limb defect. Whole exome sequencing was performed with the samples from two affected individuals. However, no other variant in candidate gene to explain the limb defects was detected. We concluded that Santos syndrome is caused by a mutation in the WNT7A gene. Functional assays, based on Luciferase activity, are in execution to test the deleterious effect of the c.934G>A variant in the WNT7A gene

A Terapia de Uso Forçado (TUF) e uma técnica se propõe a reverter o desuso aprendido e assim conduzir a plasticidade encefálica pós-AVE. Por se tratar de uma terapia restritiva, que força a utilização de um dos membros superiores e detrimento do outro essa modalidade terapêutica é passível de críticas. Sendo assim, o nosso trabalho foi estruturado para investigar se existem prejuízos no MS não acometido e ainda se propõe a analisar de maneira instrumentalizada os benefícios produzidos no MS parético. Participaram deste estudo 32 indivíduos que sofreram AVE isquêmico e que apresentavam hemiparesia. Os indivíduos foram randomizados em dois grupos de tratamento por quatro semanas consecutivas: TUF (imobilização do MS não acometido por 24 horas, durante 4 semanas) e FC (fisioterapia convencional, duas vezes por semana). A avaliação foi realizada antes do início, 2 semanas após, no final do protocolo e três meses após o término. Foram utilizadas as escalas: National Institute of Health Stroke Scale (NIHSS), Teste Motor de Wolf (WMFT), dinamometria (preensão palmar) e eletromiografia de superfície (músculos extensores do punho). Os dados do grupo TUF foram analisados por uma análise de variância de uma via e os dados da FC por um teste em t para amostras pareadas. Para a comparação intergrupos foi utilizado o teste t de Student. Foram consideradas diferenças significativas p 0,05. A análise das pontuações da NIHSS não revelou diferenças significativas na comparação intra e intergrupos. A análise dos dados da dinamometria intra e intergrupos do lado não parético, não revelou diferenças estatísticas. Para o lado parético os dados da TUF mostraram um aumento na % Kgf em relação aos dados iniciais para o lado parético (F: 2,90) e parético a direita (F:2,70). A análise dos dados de eletromiografia intra e intergrupo, do lado não parético não revelou diferenças estatísticas. Já para o lado parético, os dados da TUF mostraram um aumento de % RMS em relação aos dados iniciais para o lado parético (F:2,43) e parético a direita (F:1,67). Para os dados da WMFT, não observamos diferenças para o lado não parético no grupo TUF. Entretanto o para a FC, observamos uma diminuição do tempo de execução das atividades no lado não parético e a esquerda (t=3,26). Em relação ao lado parético, parético a direita e parético a esquerda, o grupo TUF apresentou modificações em todos as comparações (F:10,08), (F:4,24;) e (F:6,75), respectivamente. Já no grupo FC, somente para a comparação no lado parético (t=2,21). Ambos os grupos apresentam um melhor desempenho nas tarefas individuais no lado não parético. Entretanto, o grupo FC no lado não parético esquerdo apresenta uma redução do tempo na atividade cotovelo estendido em relação ao tempo final do grupo TUF (t=2,45). Em relação ao lado parético, o grupo TUF apresenta uma redução do tempo de atividade para um grande número de tarefas individuais, o que não acontece com o grupo FC. Ainda, o grupo TUF tem uma redução do tempo de execução significativa em relação ao grupo FC no lado parético, para as tarefas cotovelo estendido com peso (t=2,45) e girar chave na fechadura (t=2,67).Nosso trabalho mostra que a TUF melhora o desempenho motor do lado parético. Ainda, é segura uma vez que não observamos prejuízos motores do lado não parético. / The Forced Used Therapy (FUT) is a technique proposes to reverse learned nonuse and thus lead to brain plasticity after stroke. Because it is a restrictive therapy that forces the use of an upper limb in the detriment of another this therapeutic modality is subjected to criticism. Thus, our work was structured to investigate if there are impairments in not paretic UL and aims intends to analyze the possible benefits produced in paretic UL. The study included 32 subjects who experienced ischemic stroke and who had hemiparesis. Subjects were randomized in two treatment groups for four consecutive weeks: FUT (non-paretic UL immobilization for 24 hours to 4 weeks) and SP (standard physiotherapy twice a week). The evaluation was performed at baseline, 2 weeks after, at end of the protocol and three months follow up. We used the scales: National Institute of Health Stroke Scale (NIHSS), Wolf Motor Function Test (WMFT), dynamometer (handgrip) and surface electromyography (extensor muscles of the wrist). Data from the FUT group were analyzed by one way ANOVA and data the SP by a t-test for paired samples. For comparisons between groups, Student\'s t test was used. Significant values were considered by p 0.05. The analysis of the NIHSS scores revealed no significant differences in intragroup and intergroup comparison. Dynamometry data analysis of intra and inter group in the non-paretic side showed no statistical differences. For the paretic side, FUT data showed an increase in % Kgf relate to the initial to paretic side (F: 2.90) and paretic at the right (F: 2.70). Electromyography data analysis of intra- and intergroup, in the non-paretic side, showed no statistical differences. As for the paretic arm, the data showed an increase in % RMS of FUT compared to the initial for the paretic (F: 2.43) and right paretic (F: 1.67). For WMFT data, there were no differences for the non-paretic side in the FUT group. However, for the SP, we observed a reduction of the execution time of activities in the non-paretic side and paretic at the left (t = 3.26). In relation to the paretic, paretic, paretic to right and left, the FUT group showed changes in all comparisons (F: 10,08), (F: 4.24) and (F: 6.75), respectively. In the SP group, only for comparison in paretic (t = 2.21). Both groups perform better on individual tasks in the non-paretic side. However, the SP group in the left non-paretic side showed a reduction of time in the elbow extended activity in relation to the FUT final (t = 2.45). The FUT group for paretic side compared to the SP group has a less duration of activity for a large number of individual tasks, which does not happen with the SP group. Still, the FUT group has a significant reduction in execution time compared to the SP group in paretic hand for tasks elbow extended with weight (t = 2.45) and turn key in the lock (t = 2.67). Our work shows that the FUT improves motor performance of the paretic hand. Still, it is safe since no observed loss of the non-paretic arm.

As distrofias musculares tipo cinturas (DMC) incluem um grupo heterogêneo de doenças genéticas, caracterizadas por degeneração progressiva da musculatura esquelética pélvica e escapular, cuja herança pode ser autossômica dominante (DMC1) ou autossômica recessiva (DMC2). As formas dominantes são relativamente raras, compreendendo menos que 10% dos casos. Até o momento foram mapeados 8 locos para DMC1, (DMC1A-H), onde 3 genes já foram identificados (DMC1A-C) e 17 locos para DMC2 (DMC2A-Q), onde 16 genes já foram identificados. No presente estudo, identificamos uma família uruguaia (família 1) com 11 indivíduos afetados por DMC, distribuídos em 3 gerações, com um padrão de herança autossômico dominante. Os objetivos desse trabalho foram: mapear e refinar o loco gênico associado a uma manifestação familiar de DMC1, verificar se há co-localização da região mapeada com outras formas de DMC1 descritas na literatura e, apontar genes candidatos na região mapeada e triar mutações. Foi realizado estudo de ligação, no qual mapeou-se o loco para essa doença na região 4q13-q24 com Lod score de valor máximo 4.78 para o marcador D4S414. A região foi delimitada entre os marcadores D4S392 e D4S1572. A análise da região redefiniu o loco em 4q21.22-21.23, com uma redução de 33 Mb para 4Mb. Esse loco compreende a DMC1G (família 2), descrita anteriormente pelo nosso grupo. A triagem de mutação, realizada em amostras de afetados das duas famílias, nos permitiu encontrar uma alteração Thr141Iso no exon 5 do gene FAM175A apenas nos pacientes da família 2. Essa mesma alteração foi encontrada em 1 dos 500 controles testados, o que não nos permite excluir esse gene como um candidato para DMC1G já vez que essa frequência foi inferior a 1%. O fato dessa alteração não ter sido vista na família 1 também não nos permite excluí-lo, pois foi sequenciada apenas a região exônica e a metodologia utilizada também não nos permite verificar deleções nem duplicações. Estudos mais detalhados precisam ser realizados a fim de elucidar: (1) se a alteração desse gene é a causadora dessas DMCs ou, (2) se excluído esse gene, poderia ser o responsável. / Limb girdle muscular dystrophy (LGMD) include a heterogeneous group of genetic diseases characterized by progressive degeneration of skeletal muscles of the pelvic and scapular girdles, whose inheritance may be autosomal dominant (LGMD1) or autosomal recessive (LGMD2). The dominant forms are relatively rare, comprising less than 10% of cases. So far eight loci were mapped for LGMD1 (LGMD1A-H), where three genes have been identified (LGMD1A-C) and 17 loci for LGMD2 (LGMD2A-Q), with 16 identified genes. In this study, we analised a family from Uruguay (family 1) with 12 individuals affected by LGMD, with an autosomal dominant pattern distributed in three generations. The objectives of this study were: to map and refine the gene locus associated with a familial DMC1, check for co-location of the mapped region to other forms of DMC1 described in the literature and, to point candidate genes mapped in the region and to screen mutations. A linkage study was conducted, and we mapped the locus for this disease in the region 4q13-q24 with a maximum Lod score of 4.78 for marker D4S414. The region was defined between markers D4S392 and D4S1572. The analysis of the region has redefined the locus to 4q21.22-in 21:23, a reduction from 33 Mb to 4 Mb. This site includes LGMD1G (family 2), previously described by our group. Mutation screening, performed on samples of affected pacients from both families, allowed us to find a modification Thr141Iso in exon 5 on FAM175A gene only in patients of family 2. This same alteration was found in one of the 500 controls tested but does not allow us to exclude this gene as a candidate for LGMD1G since that frequency was less than 1%. The fact that this change was not seen in a family 1 does not allow us to exclude it either because only the exonic region was sequenced and the methodology used does not allow us to detect deletions or duplications. More detailed studies should be conducted to elucidate: (1) whether the alteration found in this gene is the cause of these DMCs, or (2) if not this gene, which could be the one responsible.

This thesis presents observations of the dynamical features of the stratosphere, mesosphere and lower thermosphere. These are made from various observational techniques and model comparisons. A focus of the work is the two-day wave at high latitudes in the MLT region. This has revealed significant wave amplitudes in both summer and winter. However, these waves are shown to have very different origins. Using satellite data, the summertime wave is found to be the classic quasi-two-day wave which maximises at mid-latitudes in the MLT region. The wintertime wave is found to be a mesospheric manifestation of an eastward-propagating wave originating in the stratosphere and likely generated by barotropic and baroclinic instabilities in the polar night jet. The horizontal winds from Meteor and MF radars have been used to measure and produce climatologies of the Lunar M2 tide at Esrange in the Arctic (68°N), Rothera and Davis in the Antarctic (68°S), Castle Eaton at mid-latitude (52°N) and Ascension Island at Equatorial latitudes (8°S). These observations present the longest period of lunar semi-diurnal tidal observations in the MLT region to date, with a 16-year dataset from the UK meteor radar. Comparisons with the Vial and Forbes (1994) lunar tidal model are also made which reveal generally good agreement. Non-migrating lunar tides have been investigated. This uses lunar tidal results from equatorial stations, including the Ascension Island (8°S) meteor radar. Also lunar tidal results from the Rothera meteor wind radar (68°S, 68°W) and the Davis MF radar (68°S, 78°E) are considered. Both of these stations are on the edge of the Antarctic continent. It is demonstrated that there are often consistent tidal phase offsets between similar latitude stations. This suggests that non-migrating modes are likely to be present in the lunar semi-diurnal tidal structure and have significant amplitudes.

Upper-limb myoelectric prostheses are controlled by muscle activity information recorded on the skin surface using electromyography (EMG). Intuitive prosthetic control can be achieved by deploying statistical and machine learning (ML) tools to decipher the user's movement intent from EMG signals. This thesis proposes various means of advancing the capabilities of non-invasive, ML-based control of myoelectric hand prostheses. Two main directions are explored, namely classification-based hand grip selection and proportional finger position control using regression methods. Several practical aspects are considered with the aim of maximising the clinical impact of the proposed methodologies, which are evaluated with offline analyses as well as real-time experiments involving both able-bodied and transradial amputee participants. It has been generally accepted that the EMG signal may not always be a reliable source of control information for prostheses, mainly due to its stochastic and non-stationary properties. One particular issue associated with the use of surface EMG signals for upper-extremity myoelectric control is the limb position effect, which is related to the lack of decoding generalisation under novel arm postures. To address this challenge, it is proposed to make concurrent use of EMG sensors and inertial measurement units (IMUs). It is demonstrated this can lead to a significant improvement in both classification accuracy (CA) and real-time prosthetic control performance. Additionally, the relationship between surface EMG and inertial measurements is investigated and it is found that these modalities are partially related due to reflecting different manifestations of the same underlying phenomenon, that is, the muscular activity. In the field of upper-limb myoelectric control, the linear discriminant analysis (LDA) classifier has arguably been the most popular choice for movement intent decoding. This is mainly attributable to its ease of implementation, low computational requirements, and acceptable decoding performance. Nevertheless, this particular method makes a strong fundamental assumption, that is, data observations from different classes share a common covariance structure. Although this assumption may often be violated in practice, it has been found that the performance of the method is comparable to that of more sophisticated algorithms. In this thesis, it is proposed to remove this assumption by making use of general class-conditional Gaussian models and appropriate regularisation to avoid overfitting issues. By performing an exhaustive analysis on benchmark datasets, it is demonstrated that the proposed approach based on regularised discriminant analysis (RDA) can offer an impressive increase in decoding accuracy. By combining the use of RDA classification with a novel confidence-based rejection policy that intends to minimise the rate of unintended hand motions, it is shown that it is feasible to attain robust myoelectric grip control of a prosthetic hand by making use of a single pair of surface EMG-IMU sensors. Most present-day commercial prosthetic hands offer the mechanical abilities to support individual digit control; however, classification-based methods can only produce pre-defined grip patterns, a feature which results in prosthesis under-actuation. Although classification-based grip control can provide a great advantage over conventional strategies, it is far from being intuitive and natural to the user. A potential way of approaching the level of dexterity enjoyed by the human hand is via continuous and individual control of multiple joints. To this end, an exhaustive analysis is performed on the feasibility of reconstructing multidimensional hand joint angles from surface EMG signals. A supervised method based on the eigenvalue formulation of multiple linear regression (MLR) is then proposed to simultaneously reduce the dimensionality of input and output variables and its performance is compared to that of typically used unsupervised methods, which may produce suboptimal results in this context. An experimental paradigm is finally designed to evaluate the efficacy of the proposed finger position control scheme during real-time prosthesis use. This thesis provides insight into the capacity of deploying a range of computational methods for non-invasive myoelectric control. It contributes towards developing intuitive interfaces for dexterous control of multi-articulated prosthetic hands by transradial amputees.

Engagement in rehabilitation, such as physiotherapy, is critical to enhanced outcomes from musculoskeletal injuries (MIs) and has been found to be related to psychosocial factors, including increased personal control, higher levels of autonomous-motivation and more problem-focused type coping strategies in sports populations. However, this has not been empirically studied in British military groups, despite MIs being the most common reason for medical discharge from the British armed forces. Military personnel are thought to cope with injury within the context of a 'military culture' that is not found in civilians. This study tested a concept of military culture being related to greater adherence to masculine norms; higher levels of perceived personal control and autonomous motivation; lower levels of emotion-focused coping strategies; a greater use of problem-focused coping strategies and better engagement in rehabilitation. Data from self-report questionnaires and physiotherapist ratings of engagement in rehabilitation, provided by two groups, was compared. Group one consisted of 16 serving male military personnel and group two of 22 committed sports men; all had MIs sustained within the past 6 months, for which they were having physiotherapy. The sports group were found to show statistically significant greater adherence to masculine norms, and use of problem-focused and emotion-focused coping strategies. No significant differences were found between the groups on perceived personal control, autonomous motivation nor engagement in rehabilitation. A military culture defined by greater adherence to masculine norms; higher levels of perceived personal control and autonomous motivation and a greater use of problem-focused coping strategies has therefore not been supported by this study. However, only sufficient power was achieved for the analysis of emotional-focused coping strategies so caution must be taken when interpreting these results. Clinical and research implications are discussed with recommendations for further work with methodological lessons learnt.

Introdução: Atletas de Powerlifting utilizam habitualmente em sua preparação física o Agachamento (AT) e o Box-Squat (BS). Conhecer as variáveis cinemáticas e eletromiográficas destes exercícios é relevante para sua prescrição. Objetivo: Comparar os efeitos agudos da utilização do Agachamento e do Box-Squat, em três diferentes amplitudes de movimento, sobre variáveis de desempenho neuromuscular, em atletas de Powerlifting. Materiais e Métodos: Dez atletas de Powerlifing (31,7±5,05 anos) participaram de duas sessões de avaliação: i) aplicação de questionário, realização de medidas antropométricas e testes de 1RM para Agachamento e Box-Squat nas condições Completo, Paralelo e Parcial; ii) Coleta do sinal eletromiográfico dos músculos Reto Femoral; Vasto Lateral; Vasto Medial; Bíceps Femoral; Glúteo Máximo; Gastrocnêmio Lateral e Eretores da Coluna, durante AT e BS com as cargas de 1RM previamente aferidas. Coleta de dados de cinemetria 2D para o cálculo da Potência Absoluta e Relativa. Resultados: A carga de 1RM (252±55 Kg) e o Índice de Força Relativa (2,66±0,43) do BS Parcial foram significativamente maiores que nas outras cinco variações de exercício. Potência Absoluta (613,25±194,80 W) e Relativa (6,48±1,86) foram maiores no AT Parcial quando comparado a BS Completo, AT Completo, AT Paralelo e BS Paralelo. A ativação EMG do Reto Femoral foi maior no BS Completo (95,48±46,82 %CIVM) comparada à AT Parcial e BS Parcial. O Glúteo Máximo foi mais ativado no AT Paralelo (175,36±101,79 %CIVM) comparado ao BS Completo (143,51±79,00 %CIVM). A ativação dos Eretores da Coluna no AT Paralelo (132,27±77,31 %CIVM) foi superior à do AT Parcial (92,09±38,28 %CIVM). Conclusão: As cargas de 1RM foram maiores em excursões articulares reduzidas, com vantagem do BS Parcial. O AT Parcial apresentou maiores valores de Potência Absoluta e Relativa. AT e BS mostraram-se equivalentes do ponto de vista da ativação muscular. / Introduction: Powerlifters commonly use Squats and Box-Squats in their training process. Knowing kinetics and kinematics of these exercises can help trainers when planning a training program. Objective: To compare kinetic and kinematics of full, parallel and partial Squats and Box-Squats performed by Powerlifters. Material and Methods: Ten Powerlifters (31,7±5,05 years) participated in two sessions of data collection: i) Survey about training and injury, Anthropometrical measures, 1RM testing for the full, parallel and partial Squats and Box-Squats; ii) Muscle activity of rectus femoris, vastus lateralis, vastus medialis, biceps femoris, gluteus maximus, lateral gastrocnemius and erector spinae over the six conditions at 100% of 1RM. Sagital plane video was recorded for power output measures. Results: Significantly higher loads were observed in Partial Box-Squat (252±55 Kg) compared to the other five situations. Overall (613,25±194,80 W) and Relative (6,48±1,86) Power Output were higher at Partial Squat when compared to Parallel and Full Squats and Box-Squats. Muscle activation of rectus femoris was significantly higher in Full Box-Squat (95,48±46,82 %MVC) compared to Partial Squats and Box-Squats. Gluteus maximus activation was higher at the Parallel Squat (175,36±101,79 %MVC) when compared to the Full Box-Squat (143,51±79,00 %MVC). Erector Spinae muscle activation was significantly higher in Parallel Squat (132,27±77,31 %MVC) in comparison to the Partial Squat (92,09±38,28 %MVC). Conclusion: Higher 1RM loads were found in Partial Range of Motion, especially in Box-Squat. Overall and Relative Power Output were higher at Partial Squats. Squats and Box-Squats showed similar muscle activation patterns.

Orientador: Carlos Alberto Hussni / Resumo: A venografia é um exame radiográfico contrastado utilizado para identificar ou avaliar a função venosa de membros, órgãos ou região anatômica. A lidocaína é um anestésico local que possui efeito vasodilatador. O objetivo do trabalho foi avaliar o efeito da lidocaína (2%), na venografia distal do membro torácico de equinos hígidos, por meio da descrição e contagem dos vasos contrastados distalmente ao membro, comparou-se a aplicação de 40 mL de contraste diatrizoato de meglumina 60% associado à lidocaína 2% com a associação de solução salina 0,9% e os volumes entre 40 e 60 mL de solução, questionando-se se a variação de volume ou a associação com a lidocaína pela vasodilatação podem diferir sobre no preenchimento venoso. Em cinco equinos adultos hígidos procedeu-se a venografia em ambos os membros torácicos com estase a partir de torniquete aplicado na região distal do rádio, aplicando-se para cada membro torácico os protocolos 40S (20 mL de meio de contraste + 20 mL de solução salina 0,9%), 40L (20 mL de meio de contraste + 20 mL de lidocaína 2%) e 60S (30 mL de meio de contraste + 30 mL de solução salina 0,9%) com intervalo de cinco dias entre cada exame. Os exames radiográficos foram realizados nas projeções dorso-palmar (DPa) e látero-medial (LM) (70 kV, 8 mAs e 70 cm distância foco-filme). As medianas foram calculadas a partir da contagem de vasos nas duas posições radiográficas e nas regiões distal de metacarpo e média das falanges proximal e média. Foi observado a distr... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Venography is a contrasted radiographic examination used to identify or evaluate venous function in limbs, organs or other anatomic regions. Lidocaine is a local anesthetic that has a vasodilator effect. The aim of this study was to evaluate the effect of lidocaine (2%), in the distal venography of the distal forelimb of horses, through the description and counting of regional distal vessels, comparing the application of contrast solution associated with lidocaine and saline solution in total volumes of 40 or 60 mL, aiming to evaluate whether the volume variation or the association with lidocaine would interfere in the results. Venography was performed on both forelimbs of five adult horses, with stasis from a tourniquet applied to the distal radius, applying three different combinations of fluids: group 40S received 20 mL of contrast + 20 mL of saline solution 0,9%; group 40L received 20 mL of contrast + 20 mL of lidocaine 2% and group 60S received 30 mL de contrast + 30 mL of solution saline 0,9%. An interval of five days between every utilization was respected. The radiographs were made in the dorsopalmar and lateromedial projections (70kV, 8 mA and 70 cm of distance). The medians were calculated using the vessel count of both radiographic projections, in the distal metacarpal and middle regions of the proximal and middle phalanges. Axial distribution to the distal phalanx was observed in all protocols, with more evidence of the larger caliber of the vessels when lidocaine... (Complete abstract click electronic access below) / Mestre

Tgf-β, Wnt, and Fgf signaling pathways are required for many developmental processes. Here, I investigated the requirement of these signaling pathways during tail regeneration and limb development in the Mexican axolotl (Ambystoma mexicanum). Using small chemical inhibitors during tail regeneration, I found that the Tgf-β signaling pathway was required from 0-24 and 48-72 hours post tail amputation (hpa), the Wnt signaling pathway was required from 0-120 hpa, and the Fgf signaling pathway was required from 0-12hpa. Tgf-β1 was upregulated after amputation and thus may mediate Tgf-β signaling pathway during tail regeneration. Both Smad-mediated and non-Smad mediated Tgf-β signaling were activated as early as 1hpa. Smad-mediated Tgf-β signaling via activated pSmad2 and pSmad3, and via phosphorylated Erk and Akt. Two different Tgf-β signaling pathway inhibitors, SB505124 and Naringenin, differentially regulated pSmad2, pSmad3, p-Erk, and p-Akt, while SB505124 and Naringenin both inhibited tail regeneration; only SB505124 reduced cell proliferation. Wnt/β-Catenin signaling was increased and was enhanced by Wnt-C59. Disruption of the Wnt signaling pathway directly or indirectly activated Erk and Akt signaling. Disruption of the Fgf signaling pathway decreased p-Erk and increased p-Akt. All three signaling pathways affected cell proliferation and mitosis during tail regeneration. The Wnt pathway inhibitor Wnt-C59 prevented forelimb bud outgrowth. The critical window for Wnt signaling regulating forelimb bud outgrowth was approximately developmental stage 40-42. Wnt signaling ligand Wnt3a and tight junction protein Zo-1 were expressed in the epidermis of the forelimb bud and both were down-regulated by Wnt-C59. Moreover, both Wnt and Fgf signaling pathways affected cell proliferation and mitosis of mesodermal cells during forelimb bud outgrowth. Overall, my results show that Tgf-β, Wnt, and Fgf signaling pathways are required for axolotl tail regeneration. All three pathways affect Erk and Akt signaling and guide cell proliferation and mitosis. The Wnt signaling pathway is required for forelimb bud outgrowth, and it appears to regulate expression of Wnt3a and Zo1, and control cell proliferation and mitosis of mesodermal cells underlying the forelimb epidermis. These data enrich understanding of signaling network dynamics that underlie tissue regeneration and vertebrate limb development.