Introdução: O aumento da rotação interna dos quadris é a causa mais comum de desvio interno dos pés na paralisia cerebral. A osteotomia de rotação externa do fêmur tem sido a forma preferencial de tratamento para os casos com aumento da anteversão femoral; no entanto, permanecem controversos os dados e fatores relacionados à recidiva do problema. Métodos: Estudo retrospectivo, com avaliação clínica e cinemática de 75 pacientes (99 osteotomias) com paralisia cerebral tipo diparesia espástica, com tempo de seguimento médio de 1 ano e 10 meses, submetidos à osteotomia de rotação externa do fêmur proximal. Os pacientes foram divididos em dois grupos, de acordo com a correção ou persistência da rotação interna do quadril durante a marcha na cinemática após a cirurgia. Os pacientes, com correção mantida na primeira avaliação, foram convocados para novo exame, realizado em média 4 anos e 5 meses após a osteotomia femoral. Os grupos foram comparados com uso dos Testes de Igualdade de Duas Proporções, Mann-Whitney e Wilcoxon. Resultados: Na primeira avaliação, realizada em média 1 ano e 10 meses após a osteotomia femoral, 33,33% dos membros tratados apresentavam persistência da rotação interna do quadril. Dos 54 pacientes com manutenção da correção na primeira avaliação, 35 (42 lados) retornaram para a segunda avaliação após em média 4 anos e 5 meses, quando foi observada recidiva da rotação interna do quadril em 9,53% dos casos. A persistência da rotação interna do quadril na primeira avaliação pós-operatória mostrou relação com o tipo de fixação interna utilizada na osteotomia femoral. O uso da placa angulada foi mais frequente nos pacientes com correção mantida, e a placa reta DCP foi mais usada no grupo de pacientes com persistência da rotação interna (p=0,033). Na segunda avaliação, a recidiva esteve relacionada com a realização da osteotomia femoral em pacientes mais jovens (p=0,032). Conclusão: A persistência da rotação interna do quadril após a realização da osteotomia de rotação externa do fêmur foi observada em um terço dos casos, e a realização da osteotomia femoral na região subtrocanteriana e fixação com placa reta DCP foi mais frequente nesse grupo de pacientes do que nos que mantiveram a correção. A recidiva da rotação interna esteve presente em 9,53% dos casos, e a idade de realização da osteotomia femoral foi menor nos pacientes com recorrência / Introduction: Hip internal rotation is the most common cause of in toeing gait in cerebral palsy and femur external derotational osteotomy has been the preferential treatment option in cases with increase of femur anteversion, however the factors related to recurrence of the problem still controversial. Methods: Retrospective study, with clinical and kinematic evaluation of 75 diparetic spastic cerebral palsy patients, with mean follow-up time of 1 year and 10 months, underwent proximal femur external derotational osteotomy. The patients were divided in two groups according the correction or persistence of hip internal rotation during gait at kinematics after surgery. Patients with correction achieved were asked to come back for a second analysis, after a mean follow-up time of 4 years and 5 months. The groups were compared using two proportions equality test, Mann-Whitney test and Wilcoxon test. Results: In the first evaluation, with mean follow-up of 1 year and 10 months, 33.33% of osteotomies shown persistent hip internal rotation. Thirty-five of 54 patients of hip internal rotation correction at first evaluation came back for the second analysis after a mean follow-up time of 4 years and 5 months, when was observed a recurrence in the 9.53% of cases. The persistence of hip internal rotation at first evaluation after surgery exhibited relation to type of internal fixation used at proximal femur. The use of blade plates was more frequent at patients with correction achieved whereas dynamic compression plates were used more frequently in the group of patients of persistent hip internal rotation (p=0.033). In the second evaluation, the recurrence was related to femur osteotomy in the earlier age (p=0.032). Conclusion: The persistent hip internal rotation after femur external derotational osteotomy was observed at 33.33% of the cases and the use of dynamic compression plate for fixation was more frequent than the group with correction achieved. The recurrence of hip internal rotation was observed at 9.53% of the cases and the femur osteotomy was performed in earlier age in this group

Introdução: A recorrência de crises epiléticas pós cirurgia para tratamento da epilepsia do lobo temporal tem sido classificada como precoce ou tardia dependendo do tempo da primeira crise depois do procedimento. Contudo, este tempo de recorrência é variado, sendo arbitrariamente definido nos artigos científicos. Objetivos: Nós desenvolvemos um modelo matemático que pode identificar pacientes com chance de recorrência de crises pós-operatórias precoces ou tardias. Após, analisamos os dois grupos para identificar as diferenças clínicas, eletrofisiológicas e de neuroimagem entre estes pacientes. Métodos: Uma coorte histórica com 247 pacientes tratados com cirurgia para epilepsia do lobo temporal foi estudada. Dentre os paciente onde as crises epiléticas retornaram, utilizamos o tempo de recorrência em uma curva ROC para avaliar com maior acurácia o melhor período para predizer o prognóstico cirúrgico a longo prazo. Com isto, dividimos os pacientes em dois grupos: os de recorrência precoce e os de recorrência tardia. Após, nós analisamos as diferenças clínicas e radiológicas entre estes pacientes. Resultados: As crises epiléticas retornaram em 107 (48.9%) pacientes. A curva ROC mostrou que 6 meses era o tempo onde o prognóstico a longo prazo poderia ser determinado com maior acurácia (AUC = 0.761; sensibilidade = 78.8%; especificidade = 72.1%). Nós observamos que nos pacientes onde a recorrência ocorreu nos primeiros 6 meses após a cirurgia, a epilepsia começou mais precocemente (OR: 6.034; CI95%: 1.056–11.013; p=0.018), estes pacientes possuíam um pior prognóstico (6.849;2.538–18.518;p=0.001), necessitaram de maior número de medicação anti-epilética após o procedimento (2.07;1.162–9.345;p=0.013) e mais freqüentemente foram submetidos a uma nova cirurgia para controle de crises (9.592;1.181–77.877;p=0.021). Nos pacientes com recorrência tardia, as crises epiléticas eram mais comumente associadas a fatores desencadeantes (9.615;3.521–26.315;p<001). Conclusão: Pacientes com recorrências de crises epiléticas precoces ou tardias possuem diferentes características que podem estar relacionadas a diferenças entre os tipos de zonas epileptogênicas, eficácia dos procedimentos cirúrgicos ou mesmo à própria epileptogenicidade. A existência de tais disparidades podem ajudar a explicar os diferentes padrões de recorrência de crises pós cirurgia para epilepsia, auxiliando no planejamento do tratamento destes pacientes a longo prazo. / Background: Recurrence of seizures after surgery for epilepsy has been generally classified as either early or late depending on the time between surgery and seizure recurrence. However, the time of seizure recurrence is variable and it has been arbitrarily defined in the literatures. Objective: Here we establish a statistical-based model for discriminating patients with early or late seizure recurrence and examine the clinical, electrophysiological, and neuroimaging differences between these two groups of patients. Methods: A historical cohort of 247 patients treated surgically for temporal lobe epilepsy was identified. In those patients who recurred, the post-operative time until seizure recurrence was examined using an ROC curve to discriminate with greater accuracy the best period for predicting the long-term prognosis of patients. This approach divided patients in two groups, those with early and those with late seizure recurrence. Following this division, we compared differences between these groups in terms of a number of clinical and radiological variables. Results: Seizures recurred in 107 (48.9%) patients. The ROC curve showed that 6 months was the time when long-term surgical outcome could be determined with best accuracy, (AUC = 0.761; sensitivity = 78.8%; specificity = 72.1%). We observed that patients with seizure recurrence during first 6 months after surgery started seizing at younger age (OR: 6.034; CI95%: 1.056–11.013; p=0.018), had a worse outcome (6.849;2.538–18.518;p=0.001), needed a higher number of antiepileptic medications after surgery (2.07;1.162–9.345;p=0.013) and were more frequently submitted to reoperations (9.592;1.181–77.877;p=0.021). Patients with late relapse more frequently had seizures associated with trigger events (9.615;3.521–26.315;p<001). Conclusion: Patients with early or late recurrence of seizures have different characteristics that might reflect diversity in the epileptogenic zone and epileptogenicity itself. These disparities might help to explain variable patterns of seizures recurrence after epilepsy surgery.

A recaída ao uso de drogas é um dos principais obstáculos para o tratamento do adicto. Um dos modelos animais mais utilizados para estudar a recaída no laboratório é o chamado de cue-induced. Embora esse modelo tenha se mostrado útil para o estudo de processos neurofisiológicos envolvidos na recaída, seu valor para a análise do controle de estímulos ambientais na dependência tem sido limitado por não distinguir a função dos estímulos discriminativos e dos reforçadores condicionados que controlam a reinstalação da resposta que foi reforçada por droga. O principal objetivo do presente estudo foi analisar os controles estabelecidos sobre as respostas de pressão à barra de ratos submetidos ao procedimento cue-induced. Foram realizados três experimentos. No Experimento 1, os animais passaram pelas três fases experimentais que caracterizam esse modelo. Na primeira fase, a resposta de pressão à barra foi treina em dois componentes distintos. Em um deles, as respostas emitidas na presença de um odor de laranja (SD1) tiveram como conseqüência a apresentação de um estímulo luminoso (Sr1) e liberação de uma solução de etanol (grupo ET) ou de sacarose (grupo SAC). Enquanto na outra, pressões à barra na presença de um odor de erva-doce (SD2) tiveram como conseqüência a apresentação um estímulo sonoro (Sr2) e liberação de água. Na segunda fase, foram realizadas sessões de extinção na ausência dos estímulos utilizados no treino. Na terceira fase os estímulos discriminativos e reforçadores condicionados foram reintroduzidos, mas as respostas de pressão à barra não foram reforçadas por etanol, sacarose ou água. Finalizado o procedimento padrão, foram realizados testes adicionais, nos quais cada estímulo utilizado no treino foi apresentado separadamente. O procedimento do Experimento 2 foi similar ao do Experimento 1, porém foram controladas duas variáveis irrelevantes para o modelo, mas associadas com as contingências experimentais: a maravalha da bandeja da caixa experimental e o acionamento do bebedouro. No Experimento 3, foi adicionada sacarose à solução de etanol e a água. Os resultados dos Experimentos 1 e 2 mostraram que Sr1 foi efetivo em reinstalar a resposta de pressão à barra nos testes de reinstalação realizados, enquanto SD1 foi inconsistente em reinstalar essa resposta. A apresentação de SD2 e Sr2 não reinstalou a resposta. Os dados obtidos no Experimento 3 foram inconclusivos quanto ao controle exercido pelos estímulos olfativos, luminosos e sonoros. Os resultados parecem sugerir que o modelo animal cue-induced, tipicamente usado para estabelecer linhas de base de controle discriminativo sobre a auto-administração de drogas, pode não ser adequado para tal finalidade. No entanto, ainda são necessários refinamentos experimentais para a obtenção de resultados mais acurados. / The relapse into drug use is one of the key obstacles for addict treatment. One of the animal models most used for relapse studies in laboratory is the so called cue-induced. Even though this model has been proven to be useful for neurophysiologic processes related to relapse, its value for analyzing environment stimulus control on addiction is considered to be limited because it does not distinguish the function of discriminative stimulus and of conditioned reinforcer which control the reinstatement of the response that was reinforced by the use of drugs. The main objective of this study was to analyze the established controls over the lever pressure responses of rats submitted to the cue-induced procedure. They were subjected to three different experiments. On the first one the animals were exposed to the three different experimental stages that characterize a cue-induced procedure. At the first experimental phase, lever press response was trained over two different components. In one of them, the response to an orange odor (SD1) had as a consequence the appearance of a luminous stimulus (Sr1) and the release of ethanol (ET group) or a sucrose solution (SAC group). While in the other one, lever press in the presence of a anise odor had as a consequence the appearance of a sonorous stimulus accompanied by water release. At the second phase, there were conducted extinction sessions in the lack of the stimuli used on the training phase. And finally, at the third phase, the discriminative stimulus and conditioned reinforcer were reintroduced. Nevertheless, the lever press response was not reinforced by ethanol, sucrose or water. By the time the standard procedure was over, additional tests were run, where each stimuli used on the training phase were presented to the rats separately. The second experiment procedure was similar to the one employed at the first experiment, however two irrelevant variables for the model were controlled for, but these were associated with the experimental contingencies: the sawdust on the experimental box trail and the drinking fountain when put into action. At the third experiment, sucrose was added to the ethanol solution and also to the water. The results from the two first experiments showed that Sr1 was effective in reinstate the lever pressure response verified at the reinstatement tests, whereas SD1 was not successful in doing so. Neither the introduction of SD2 nor Sr2 reinstate the response. The data obtained by Experiment 3 was not conclusive in regards to the control imposed by the olfactory, luminous and sonorous stimuli. The results suggest that the cue-induced procedure, typically used to establish baselines for discriminative control over drugs self-administration, may not be in fact the most suitable one for this purpose. Nonetheless, there is still a need to refine the experiment in order to reach more accurate and conclusive results.

癌症復發往往伴隨著耐藥性和轉移率的增加。目前我們仍未完全瞭解確切的腫瘤逃脫機制。皮下無水酒精注射（PEI）已經被用於治療肝細胞癌（HCC）幾十年，而PEI治療後的癌症復發仍然是該方法的一個主要限制。最近有許多證據表明癌細胞能夠逆轉化學誘導的細胞凋亡過程而得以存活，這有可能是其中一個導致癌細胞復發的原因。這篇論文的重點在於研究肝癌細胞HepG2經歷乙醇誘導凋亡事件後存活下來的後果。 / 這個研究首先證實肝癌細胞 HepG2能從乙醇誘導凋亡事件後存活下來。然後我們對存活下來的肝癌細胞HepG2進行增殖率，耐藥性，運動性以及侵襲性的研究。結果表明，存活下來的HepG2有46%的乙醇耐藥性和84%的高運動性。然後爲了發現存活下來的HepG2是否對其他臨床常用藥物也同樣具有耐藥性，4種臨床常用藥物包括阿黴素，紫杉醇，順鉑，5-氟尿嘧啶（5Fu）均被用於測試。有趣的是，存活下來的HepG2對5-氟尿嘧啶變得更加敏感，平均敏感性下降了58.2%。 / 總的來說，我們的研究結果表明肝癌細胞可從乙醇誘導凋亡事件中恢復過來。此外，存活下來的細胞變得更具有耐藥性和侵入性。這種恢復過程可能是導致癌症復發的原因之一。出乎意料的是，雖然所有存活下來的細胞對乙醇具耐受性，但是它們對於5-氟尿嘧啶均變得更加敏感。這些結果表明，乙醇和5-氟尿嘧啶的聯合治療可能有助於提高PEI治療效果從而預防肝癌癌症復發。 / Cancer relapse, associated with increased drug resistance and higher rate of metastasis, often occurs after chemotherapy. The cancer escape mechanisms are still incompletely understood. Percutaneous ethanol injection (PEI) has been used for treating hepatocellular carcinoma (HCC) for decades, but the recurrence after PEI treatment remains a major limitation. Recently there are mounting evidences showing that cancer cells could survive from chemical-induced apoptosis, suggesting a potential route through which cancer relapse may occur. This thesis focuses on the consequences of the recovery of HepG2 cells from ethanol-induced apoptotic event. / This study verified that HepG2 cells could recover from ethanol-induced apoptosis. Proliferation rate, drug resistance, motility and invasiveness were investigated in recovered HepG2 cells. On average, the recovered HepG2 cell clones were found to be 46% more resistant to ethanol and 84% higher in motility than the parental cell clones. And then four commonly used clinical drugs were assayed to determine whether the recovered cell clones were also resistant to other clinical drugs, including doxorubicin, docetaxel, cisplatin and 5-fluorouracil (5-Fu). Interestingly, the recovered clones became 58.2% more sensitive to 5-fluorouracil on average. / In conclusion, our findings showed that HepG2 cells can recover from ethanol-induced apoptotic event. In addition, some cell clones recovered from apoptosis became more resistant to ethanol and some became more invasive. Such recovery might be one of the reasons causing cancer recurrence. Unexpectedly, although the recovered cell clones were more resistant to ethanol, they became more sensitive to 5-Fu treatment. These results indicated that ethanol-5-Fu combined treatment might be useful in enhancing the PEI treatment and preventing HCC cancer recurrence. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Wang, Shanshan. / Thesis (Ph.D.) Chinese University of Hong Kong, 2014. / Includes bibliographical references (leaves 115-130). / Abstracts also in Chinese.

O presente estudo observou e avaliou retrospectivamente o índice de recidiva após cirurgia ortognática para avanço maxilar em pacientes com fissura de lábio e palato. A amostra foi composta por telerradiografias laterais analisadas através de traçados cefalométricos e imagens digitais tridimensionais de modelos de estudo de 17 pacientes de ambos os sexos (10 pacientes do sexo feminino e 07 pacientes do sexo masculino), com idade entre 17 e 33 anos. Os traçados cefalométricos digitais foram avaliadas em: T1 pré-operatório; T2 pós-operatório imediato e T3 pós-operatório de seis meses a 1 ano. A análise cefalométrica digital determinou as medidas de forma linear para possíveis mudanças verticais e horizontais no pós-operatório da cirurgia ortognática para avanço maxilar. Os modelos de estudo digitalizados foram avaliados nas seguintes fases: F1 préoperatório; F2 pós-operatório de seis meses a 1 ano e F3 pós operatório de 1 até 2 anos, nos planos frontal e lateral. Verificou-se ainda nos modelos digitalizados, a linha média dentária, trespasse vertical (plano frontal) e a relação pré-molar nos lados direito e esquerdo e trespasse horizontal (plano lateral). As análises dos arcos dentários foram realizadas diretamente nas imagens escaneadas, por meio do Scanner 3Shapes R700TM e avaliadas pelo 3D Software OrthoAnalyzerTM. Um avaliador previamente calibrado e treinado fez as avaliações. A análise estatística descritiva foi realizada com valores de média, desvio-padrão e porcentagem. O teste ANOVA de medidas repetidas foi aplicado nas variáveis estudadas (movimento vertical, movimento horizontal, trespasse horizontal, trespasse vertical e linha média dentária) para comparar os três tempos determinantes. Como verificou-se significância estatística nestas diferenças, o teste Tukey foi aplicado para avaliar os grupos entre si. O nível de significância de 5% foi adotado para todas as análises. Os resultados mostraram que na cefalometria digital o movimento vertical apresentou diferença estatisticamente significativa entre T2 e T3 (p=0,002). A relação pré-molar dos lados direito e esquerdo revelou que os pacientes apresentavam em F2, ¼ classe II e classe I, 29,4% e 23,5%, e em F3 classe I, 58,8% e 70,6%, respectivamente Donde conclui-se que houve recidiva na cefalometria quanto ao movimento vertical, após cirurgia ortognática para avanço maxilar, sem recidiva nos demais parâmetros avaliado / This observational study evaluated retrospectively forms the recurrence rate after orthognathic surgery for maxillary advancement in patients with cleft lip and palate. The sample consisted of radiographs with lateral cephalometric tracing and three-dimensional digital images of 17 patients study models of both genders (10 female patients and 07 male patients), aged between 17 and 33 years. The cephalometries were evaluated: T1 preoperative; T2 - immediate postoperative period and T3 - postoperative six months to 1 year. The digital cephalometric analysis determined the measures linearly for possible vertical and horizontal changes in the postoperative period of orthognathic surgery for maxillary advancement. Study models, scanned, were evaluated in the following phases: F1 - preoperative; F2 - postoperative six months to 1 year and F3 - postoperative 1 to 2 years, in the frontal and lateral planes. It was also found on scanned models, the dental midline, overbite, overjet (frontal plane) and pre-molar relationship, on the right and left sides (lateral plane). The analysis of dental arches were made directly on the scanned images through the scanner 3Shape\'s R700TM and evaluated by 3D Software OrthoAnalyzerTM. A calibrated and trained evaluator evaluations. Descriptive statistical analysis was performed with mean values, standard deviation and percentage. The ANOVA test for repeated measures was applied to the variables (vertical movement, horizontal movement, overjet, overbite and dental midline) to compare the times. As there was statistical significance in these differences, the Tukey test was used to evaluate the groups together. The 5% significance level was adopted for all analyzes. The results showed that the cephalometry vertical movement showed a statistically significant difference between T2 and T3 (p=0.002). The premolar ratio of the right and left sides showed that patients had in F2, ¼ class II and class I, 29.4%, and 23.5%, and F3 class I 58.8% and 70.6%, respectively. It is concluded that there was recurrence in cephalometrics as the vertical movement after orthognathic surgery for maxillary advancement, without recurrence in the remaining parameters

Introdução: O aumento da rotação interna dos quadris é a causa mais comum de desvio interno dos pés na paralisia cerebral. A osteotomia de rotação externa do fêmur tem sido a forma preferencial de tratamento para os casos com aumento da anteversão femoral; no entanto, permanecem controversos os dados e fatores relacionados à recidiva do problema. Métodos: Estudo retrospectivo, com avaliação clínica e cinemática de 75 pacientes (99 osteotomias) com paralisia cerebral tipo diparesia espástica, com tempo de seguimento médio de 1 ano e 10 meses, submetidos à osteotomia de rotação externa do fêmur proximal. Os pacientes foram divididos em dois grupos, de acordo com a correção ou persistência da rotação interna do quadril durante a marcha na cinemática após a cirurgia. Os pacientes, com correção mantida na primeira avaliação, foram convocados para novo exame, realizado em média 4 anos e 5 meses após a osteotomia femoral. Os grupos foram comparados com uso dos Testes de Igualdade de Duas Proporções, Mann-Whitney e Wilcoxon. Resultados: Na primeira avaliação, realizada em média 1 ano e 10 meses após a osteotomia femoral, 33,33% dos membros tratados apresentavam persistência da rotação interna do quadril. Dos 54 pacientes com manutenção da correção na primeira avaliação, 35 (42 lados) retornaram para a segunda avaliação após em média 4 anos e 5 meses, quando foi observada recidiva da rotação interna do quadril em 9,53% dos casos. A persistência da rotação interna do quadril na primeira avaliação pós-operatória mostrou relação com o tipo de fixação interna utilizada na osteotomia femoral. O uso da placa angulada foi mais frequente nos pacientes com correção mantida, e a placa reta DCP foi mais usada no grupo de pacientes com persistência da rotação interna (p=0,033). Na segunda avaliação, a recidiva esteve relacionada com a realização da osteotomia femoral em pacientes mais jovens (p=0,032). Conclusão: A persistência da rotação interna do quadril após a realização da osteotomia de rotação externa do fêmur foi observada em um terço dos casos, e a realização da osteotomia femoral na região subtrocanteriana e fixação com placa reta DCP foi mais frequente nesse grupo de pacientes do que nos que mantiveram a correção. A recidiva da rotação interna esteve presente em 9,53% dos casos, e a idade de realização da osteotomia femoral foi menor nos pacientes com recorrência / Introduction: Hip internal rotation is the most common cause of in toeing gait in cerebral palsy and femur external derotational osteotomy has been the preferential treatment option in cases with increase of femur anteversion, however the factors related to recurrence of the problem still controversial. Methods: Retrospective study, with clinical and kinematic evaluation of 75 diparetic spastic cerebral palsy patients, with mean follow-up time of 1 year and 10 months, underwent proximal femur external derotational osteotomy. The patients were divided in two groups according the correction or persistence of hip internal rotation during gait at kinematics after surgery. Patients with correction achieved were asked to come back for a second analysis, after a mean follow-up time of 4 years and 5 months. The groups were compared using two proportions equality test, Mann-Whitney test and Wilcoxon test. Results: In the first evaluation, with mean follow-up of 1 year and 10 months, 33.33% of osteotomies shown persistent hip internal rotation. Thirty-five of 54 patients of hip internal rotation correction at first evaluation came back for the second analysis after a mean follow-up time of 4 years and 5 months, when was observed a recurrence in the 9.53% of cases. The persistence of hip internal rotation at first evaluation after surgery exhibited relation to type of internal fixation used at proximal femur. The use of blade plates was more frequent at patients with correction achieved whereas dynamic compression plates were used more frequently in the group of patients of persistent hip internal rotation (p=0.033). In the second evaluation, the recurrence was related to femur osteotomy in the earlier age (p=0.032). Conclusion: The persistent hip internal rotation after femur external derotational osteotomy was observed at 33.33% of the cases and the use of dynamic compression plate for fixation was more frequent than the group with correction achieved. The recurrence of hip internal rotation was observed at 9.53% of the cases and the femur osteotomy was performed in earlier age in this group

Prosthetic joint infection (PJI) is an emergent concern given the wide usage of prosthetic joints in old and young population to assist with activities of daily living. While the public health burden of PJI appears to be relatively low compared with other potentially fatal infections such as blood stream infections, PJI is associated with excess morbidity and steep healthcare costs. Appropriate and timely diagnosis and management are crucial in preventing poor clinical outcomes and restoring adequate function in patients with PJI. There is lack of studies using robust epidemiologic methods to evaluate effectiveness of existing treatment protocols for PJI. We conducted retrospective studies using the Veterans Affairs (VA) database using data from 123 VA hospitals between 2003 and 2012. We also abstracted clinical data from VA medical records to achieve the objectives of this research. The effectiveness of an antibiotic — rifampin and a surgical management – exchange arthroplasty was assessed in separate studies. These treatments were adjudicated based on their effectiveness in prevention of PJI recurrence and two-year postoperative mortality, respectively. Seven hundred thirty-one of the 2838 patients with first episode of PJI were treated with surgery and medical management for Staphylococcus aureus PJI and were retained in the thesis dataset. In the first study, we compared 300 patients treated with rifampin for the first 42 days of treatment period to 364 patients treated with antibiotics other than rifampin during the 42 days (unexposed). Overall, 255 patients (38.4%) were observed to have a treatment failure defined as recurrence of S. aureus PJI with or without a repeat surgery or death in the 90 days after surgery for the PJI. The rifampin-treated and unexposed groups did not differ on time to treatment failure (p=0.92). It was noted that patients treated with a less invasive surgery that resulted in retention of the infection prosthesis with removal of infected tissue and rifampin treatment had lower risk for treatment failure compared to patients with similar surgery but not treated with rifampin (HR=0.79, 95%CI 0.52-1.20). We also observed that patients who had surgery for removal of the infected prosthesis and were treated with rifampin had significantly greater risk for treatment failure compared to those treated with the prosthesis removal surgery but no rifampin. In our second study we further analyzed this research question in depth using advanced epidemiologic methods to attenuate any bias in our previous findings. We noted that the groups did not differ in their risk for treatment failure after matching patients on their probability of receiving rifampin treatment (HR=1.08, 95%CI 0.71-1.65). In addition, we observed that patients whose treatment decision with rifampin was determined by the rifampin prescription rate in the treating facility substantially benefited with use of rifampin antibiotic for S. aureus PJI. In the third study we assessed the effectiveness of a surgery — exchange arthroplasty (involves removal of infected prosthesis and insertion of new prosthesis) to reduce the risk of death two years after surgery in a sample of 566 S. aureus PJI patients. Patients with this procedure were compared to patients treated with retention of their infected prosthesis and removal of infected tissue (DAIR). Overall, 90 patients (15.9%) died in the 2 years after surgery. Of these, 14 (9.9%) died after exchange surgery while 76 (17.9%) died after the DAIR procedure. We observed that the exchange surgery reduced the risk for death by almost 60% compared to the DAIR (OR=0.42, 95%CI 0.19-0.89). In conclusion, epidemiological studies conducted as part of this thesis identified considerable burden of treatment failure (38.4%) and all-cause mortality (15.9%) among veterans treated for S. aureus PJI. Rifampin combination antibiotic regimen was not observed to be effective in reducing the burden of the infection, in comparison to other antibiotics. Exchange arthroplasty reduced the risk for death in old veteran patients compared to a less invasive but potentially life-threatening procedure such as DAIR. Choice of treatment should be made on a case-by-case basis for patients with S. aureus PJI after thorough consideration of patient characteristics.

Behavioral momentum theory provides a conceptual framework for the study of the recurrence of previously extinguished operant behavior. Commonly referred to as treatment relapse, this is the failure to maintain treatment gains (e.g., reductions in challenging behavior) when there is a change in conditions under which these gains were achieved. One treatment relapse paradigm previously examined in basic and applied research is reinstatement. Reinstatement of challenging behavior has been shown to occur when functional reinforcers are delivered on a fixed-time schedule following extinction of challenging behavior. Although examinations appropriate behavior have applied value, analyses of reinstatement have been conducted almost exclusively with challenging behavior. During the current study, a reinstatement methodology was applied to communicative responses with five children diagnosed with developmental disabilities who exhibited comorbid communication deficits, as well as challenging behavior maintained by positive reinforcement. In the first phase of the reinstatement evaluation, each child received functional communication training (FCT) within a positive reinforcement context within a two-component multiple schedule design with each schedule paired with a distinct communicative response. After achieving steady-state responding in the first phase, in which all participants were independently emitting both communicative responses, all appropriate communication was placed on extinction in the second phase. Extinction continued until rates of appropriate communication were at or near zero. In the third phase, positive reinforcement was delivered and the recurrence of appropriate communication was evaluated. For two of five participants, communicative responding recurred following the fixed-time delivery of the functional reinforcer, indicating a successful demonstration of reinstatement. For three of five participants, communicative responding recurred prior to the delivery of fixed-time reinforcement, indicating that an alternative recurrence phenomenon likely occurred. These results suggest that reinstatement methodologies can be applied to cases in which FCT treatment failures have occurred to efficiently restore clinical gains for some participants. Implications for clinical practice and future directions of this line of research are discussed.

<p>The treatment of rectal cancer is complex and comprises: diagnostic measures; different preoperative treatments; a multitude of surgical and technical choices; possibilities of postoperative treatments and postoperative care and follow up. In this thesis, some aspects of this complex paradigm have been further investigated. One of the most feared complications after rectal cancer surgery is anastomotic leakage. The risk of anastomotic leakage is affected by non-influenceable factors related to the tumour and the patient. In the first paper, the risk of anastomotic leakage in relation to a surgical instrument, the circular stapler, was investigated. The risk of leakage was 7% or 11%, depending on the choice of instrument. In the second paper, a long-term evaluation of survival and local recurrence rates in the Swedish Rectal Cancer Trial was made. Randomisation was to either preoperative radiotherapy followed by surgery or surgery alone. After 13 years median follow-up, survival was 38% in the radiotherapy group and 30% in the surgery alone group. Differences in local recurrence rates were seen in all stages. Most rectal cancer operations carry a high risk of morbidity and mortality. For early stage cancers, a local procedure may be sufficient and in the third paper, population-based results of local excision of rectal cancer were explored. In stage I, cancer specific survival was the same after local excision as after major resection, but the relative survival was lower. The risk of local recurrence was higher after local excision than after resections. In the fourth paper, differences in survival rates in the Nordic countries and Scotland were investigated. The relative excess risk of death was highest in Denmark, but only in the first 90 postoperative days. </p><p>Through applying already existing knowledge and successively introducing new treatments, the results for rectal cancer treatment will be further improved.</p>

In this paper we present an approach to recover the dynamics from recurrences of a system and then generate (multivariate) twin surrogate (TS) trajectories. In contrast to other approaches, such as the linear-like surrogates, this technique produces surrogates which correspond to an independent copy of the underlying system, i. e. they induce a trajectory of the underlying system visiting the attractor in a different way. We show that these surrogates are well suited to test for complex synchronization, which makes it possible to systematically assess the reliability of synchronization analyses. We then apply the TS to study binocular fixational movements and find strong indications that the fixational movements of the left and right eye are phase synchronized. This result indicates that there might be one centre only in the brain that produces the fixational movements in both eyes or a close link between two centres.