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The anterior cruciate ligament (ACL) plays an important role in knee joint stability, and unfortunately is one of the most commonly injured knee joint structures. The muscles surrounding the knee are also critical for stabilising the knee joint and their activations are altered following ACL injury. Despite the fact that ACL injuries are up to 8 times more likely to occur in females compared to males, there is limited research evaluating the effects of sex on how ACL-deficient individuals adjust neuromuscular control strategies during varying loading conditions. In order to have clinicians implement optimal rehabilitation strategies for ACL-deficient males and females, it is crucial to understand the adaptive functional strategies that are taking place once an ACL injury has occurred. The purpose of this thesis was therefore to provide objective and quantitative measurements describing the functional roles of muscles surrounding the knee. This was accomplished and outlined in this thesis through two chapters in manuscript format and summarised below. i) Sex and ACL-deficiency influence functional muscle roles during an isometric, weight-bearing, force-generation task First, the functional roles of muscles were quantified through the assessment of muscle activations during a series of multi-directional force-production tasks in ACL-deficient males and females while weight bearing. A highly controlled, isometric, force-matching task, whereby participants modulated ground reaction forces in various combinations of sagittal and frontal plane loads was used to quantify force-generation strategies (muscle activations and functional role) of the knee joint. Mean activation magnitudes and profile patterns from 10 muscles in the lower extremity (rectus femoris, vastus lateralis, vastus medialis, biceps femoris, semitendinosus, lateral gastrocnemius, medial gastrocnemius, tensor fascia latae, adductor muscle group, and gluteus medius) were recorded using wireless electromyography (EMG) sensors. Their activations were quantified with an orientation analysis to determine if differences in functional muscle roles existed between four groups; healthy female controls, healthy male controls, ACL-deficient females, and ACL-deficient males. Overall, different functional muscle roles were found between groups. Healthy male controls activated their muscles the most specifically; females with ACL-deficiency activated their muscles the least specifically, while healthy female controls and males with ACL-deficiency shared similar functional muscle roles. This suggests that there was a specificity hierarchy in the ability, or efficiency, to modulate the activation of muscles about the knee joint when exposed to various directional loading conditions. ii) Associations between subjective measures of knee dysfunction and measures of ground reaction forces in ACL-deficient males and females Correlational relationships were evaluated between perceived knee joint function and functional capacity of the knee joint. These relationships were calculated between patient reported outcome measures (PROM) from commonly used knee assessment scoring scales maximal generated forces in the sagittal and frontal planes. Both ACL-deficient groups had significantly lower perceived knee joint function compared to healthy controls. A trend towards significance was observed in the ability to generate maximum forces in the sagittal and frontal planes, with ACL-deficient females generating smaller maximal posterior GRFs compared to healthy females. Only two statistically significant correlations (both for ACL-deficient females) were found between maximal medial GRFs and patient reported outcome measures from the Lysholm and Tegner scoring scales. This indicates that there may be a discrepancy in the sensitivity of subjective outcome measures between sexes and their corresponding ability to generate maximum GRFs. In conclusion, sex differences exist in subjective outcome measures and the functional strategy of neuromuscular control of the knee joint both before and after ACL-injury. The results of this thesis indicate the need for sex-specific tailoring of rehabilitation programs, thus providing an opportunity to improve the success rate of rehabilitation following ACL-injury. Moreover, sensitivity of subjective outcome measures and their relation to simple, practical, functional tasks between sexes warrants further investigations.

Bone bruise lesions (BBL) are documented on MRIs diagnosing acute knee ligament injury (AKLI). Recent evidence has indicated that a majority of patients that sustain an AKLI, especially anterior cruciate ligament (ACL) knee injury, will develop post-traumatic osteoarthritis (PTOA) 10-20 years following injury. It has been proposed that the initial damage sustained to the articular cartilage overlying BBL causes a cascade of events that may result in PTOA. Researchers have proposed a modification to treatment protocols for more severe BBL, or have stressed the need for the development of protective therapies to protect the articular cartilage. However, there are limited tools available to evaluate the clinical outcome of articular cartilage overlying BBL. Furthermore, damage to the cartilage overlying BBL may be different according to differing BBL severities. Therefore, the use of a cartilage degradation biomarker, serum cartilage oligomeric matrix protein (sCOMP) and the use of a BBL severity classification system may be useful to determine if differences exist between patients with and without BBL, and with differing BBL severities. The purpose of this dissertation was to investigate the utility of sCOMP as a biomarker for acute articular cartilage damage. The purposes of these studies were to determine the inter and intraday reliability of this marker, to document sCOMP longitudinally in collegiate athletes and following AKLI, and to determine if differences in sCOMP and self-reported pain and function exist for patients with and without BBL, and differing BBL following AKLI. The results of these studies indicated sCOMP measures had strong inter and intraday reliability. Additionally, exercise does seem to influence sCOMP levels; however, these elevations may not be clinically meaningful. Furthermore, sCOMP levels were not different between patients with BBL and without, and between differing BBL severities. The results of these studies support the use of a BBL severity classification for future research studies in order to further elucidate the outcomes of these lesions.

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Introdução: A entorse do tornozelo com lesão ligamentar é uma patologia muito prevalente nos ambulatórios de traumatologia. Objetivos: Considerando que inúmeros Municípios brasileiros não dispõem de aparelhos de ressonância nuclear magnética e devido ao alto custo desse exame, este trabalho avaliou a Radiografia de Estresse (RE) do tornozelo no diagnóstico das lesões ligamentares crônicas do complexo lateral do tornozelo, confirmados através da ressonância nuclear magnética (RNM). Métodos: Foram empregados os dois métodos de diagnóstico em 31 pacientes, de ambos os sexos, com idade entre 18 e 60 anos, que apresentaram entorse do tornozelo e lesão do complexo lateral do tornozelo retrospectivamente, com mais de 30 dias de evolução e que apresentavam alguma queixa clínica no tornozelo. Resultados: Dos 31 pacientes avaliados, 100% apresentaram lesão do ligamento fíbulo-talar anterior (LFTA) na RNM, e 14 pacientes (45%) apresentaram lesão do ligamento fíbulo-talar anterior e ligamento fíbulo-calcâneo (LFC). Na Radiografia de Estresse, evidenciou-se que 27 pacientes (87%) apresentavam algum grau de lesão ligamentar. Quando se avaliaram os 14 pacientes com lesão no ligamento fíbulo-talar anterior e fíbulo-calcâneo, a RE permitiu um diagnóstico positivo em 13 casos (92,8%). Conclusão: A Radiografia de Estresse é uma metodologia importante e de baixo custo no diagnóstico das lesões crônicas do complexo lateral do tornozelo. / Introduction: Ankle sprain with ligament injury is a very prevalent disease in ambulatory trauma. Purposes: Considering that many Brazilian towns do not have the nuclear magnetic resonance imaging (MRI) machines and the high cost of this examination, this study has evaluated the effectiveness of ankle stress radiographies (SR) in the diagnosis of chronic ligament injuries of the lateral ankle complex in patients previously diagnosed by clinical examination and confirmed by MRI. Methods: We have used both methods of diagnosis in 31 patients of both sexes, aged between 18 and 60, who had both an ankle sprain and lateral ankle complex injury retrospectively for more than 30 days and who had some clinical complaints. Results: From the 31 cases evaluated by MRI, 100% showed anterior talofibular ligament (ATFL) injury while 45% (14 patients) showed anterior talofibular ligament (ATFL) injury and calcaneofibular ligament (CFL) injury. On stress radiographies we have noticed that 27 patients (87%) had some degree of ligament injury. When we assessed 14 patients with anterior talofibular ligament (ATFL) injury and calcaneofibular ligament (CFL), the SR has given a positive diagnosis in 13 cases (92.8%). Conclusion: Stress radiography is an important and a low cost methodology in the diagnosis of chronic lesions of the lateral ankle complex.

Introdução: A entorse do tornozelo com lesão ligamentar é uma patologia muito prevalente nos ambulatórios de traumatologia. Objetivos: Considerando que inúmeros Municípios brasileiros não dispõem de aparelhos de ressonância nuclear magnética e devido ao alto custo desse exame, este trabalho avaliou a Radiografia de Estresse (RE) do tornozelo no diagnóstico das lesões ligamentares crônicas do complexo lateral do tornozelo, confirmados através da ressonância nuclear magnética (RNM). Métodos: Foram empregados os dois métodos de diagnóstico em 31 pacientes, de ambos os sexos, com idade entre 18 e 60 anos, que apresentaram entorse do tornozelo e lesão do complexo lateral do tornozelo retrospectivamente, com mais de 30 dias de evolução e que apresentavam alguma queixa clínica no tornozelo. Resultados: Dos 31 pacientes avaliados, 100% apresentaram lesão do ligamento fíbulo-talar anterior (LFTA) na RNM, e 14 pacientes (45%) apresentaram lesão do ligamento fíbulo-talar anterior e ligamento fíbulo-calcâneo (LFC). Na Radiografia de Estresse, evidenciou-se que 27 pacientes (87%) apresentavam algum grau de lesão ligamentar. Quando se avaliaram os 14 pacientes com lesão no ligamento fíbulo-talar anterior e fíbulo-calcâneo, a RE permitiu um diagnóstico positivo em 13 casos (92,8%). Conclusão: A Radiografia de Estresse é uma metodologia importante e de baixo custo no diagnóstico das lesões crônicas do complexo lateral do tornozelo. / Introduction: Ankle sprain with ligament injury is a very prevalent disease in ambulatory trauma. Purposes: Considering that many Brazilian towns do not have the nuclear magnetic resonance imaging (MRI) machines and the high cost of this examination, this study has evaluated the effectiveness of ankle stress radiographies (SR) in the diagnosis of chronic ligament injuries of the lateral ankle complex in patients previously diagnosed by clinical examination and confirmed by MRI. Methods: We have used both methods of diagnosis in 31 patients of both sexes, aged between 18 and 60, who had both an ankle sprain and lateral ankle complex injury retrospectively for more than 30 days and who had some clinical complaints. Results: From the 31 cases evaluated by MRI, 100% showed anterior talofibular ligament (ATFL) injury while 45% (14 patients) showed anterior talofibular ligament (ATFL) injury and calcaneofibular ligament (CFL) injury. On stress radiographies we have noticed that 27 patients (87%) had some degree of ligament injury. When we assessed 14 patients with anterior talofibular ligament (ATFL) injury and calcaneofibular ligament (CFL), the SR has given a positive diagnosis in 13 cases (92.8%). Conclusion: Stress radiography is an important and a low cost methodology in the diagnosis of chronic lesions of the lateral ankle complex.

Introdução: A entorse do tornozelo com lesão ligamentar é uma patologia muito prevalente nos ambulatórios de traumatologia. Objetivos: Considerando que inúmeros Municípios brasileiros não dispõem de aparelhos de ressonância nuclear magnética e devido ao alto custo desse exame, este trabalho avaliou a Radiografia de Estresse (RE) do tornozelo no diagnóstico das lesões ligamentares crônicas do complexo lateral do tornozelo, confirmados através da ressonância nuclear magnética (RNM). Métodos: Foram empregados os dois métodos de diagnóstico em 31 pacientes, de ambos os sexos, com idade entre 18 e 60 anos, que apresentaram entorse do tornozelo e lesão do complexo lateral do tornozelo retrospectivamente, com mais de 30 dias de evolução e que apresentavam alguma queixa clínica no tornozelo. Resultados: Dos 31 pacientes avaliados, 100% apresentaram lesão do ligamento fíbulo-talar anterior (LFTA) na RNM, e 14 pacientes (45%) apresentaram lesão do ligamento fíbulo-talar anterior e ligamento fíbulo-calcâneo (LFC). Na Radiografia de Estresse, evidenciou-se que 27 pacientes (87%) apresentavam algum grau de lesão ligamentar. Quando se avaliaram os 14 pacientes com lesão no ligamento fíbulo-talar anterior e fíbulo-calcâneo, a RE permitiu um diagnóstico positivo em 13 casos (92,8%). Conclusão: A Radiografia de Estresse é uma metodologia importante e de baixo custo no diagnóstico das lesões crônicas do complexo lateral do tornozelo. / Introduction: Ankle sprain with ligament injury is a very prevalent disease in ambulatory trauma. Purposes: Considering that many Brazilian towns do not have the nuclear magnetic resonance imaging (MRI) machines and the high cost of this examination, this study has evaluated the effectiveness of ankle stress radiographies (SR) in the diagnosis of chronic ligament injuries of the lateral ankle complex in patients previously diagnosed by clinical examination and confirmed by MRI. Methods: We have used both methods of diagnosis in 31 patients of both sexes, aged between 18 and 60, who had both an ankle sprain and lateral ankle complex injury retrospectively for more than 30 days and who had some clinical complaints. Results: From the 31 cases evaluated by MRI, 100% showed anterior talofibular ligament (ATFL) injury while 45% (14 patients) showed anterior talofibular ligament (ATFL) injury and calcaneofibular ligament (CFL) injury. On stress radiographies we have noticed that 27 patients (87%) had some degree of ligament injury. When we assessed 14 patients with anterior talofibular ligament (ATFL) injury and calcaneofibular ligament (CFL), the SR has given a positive diagnosis in 13 cases (92.8%). Conclusion: Stress radiography is an important and a low cost methodology in the diagnosis of chronic lesions of the lateral ankle complex.

Anterior cruciate knee ligament injuries are common and well known, especially amongst athletes.These injuries often require surgeries and long rehabilitation programs, and can lead to functionloss and re-injuries (Marshall et al., 1977). This work aims to explore the possibility of applyingsupervised classification on knee functionality, using different types of models, and testing differentdivisions of classes. The data used is gathered through a performance test, where individualsperform one-leg hops with motion sensors attached to their bodies. The obtained data representsthe position over time, and is considered functional data.With functional data analysis (FDA), a process can be analysed as a continuous function of time,instead of being reduced to finite data points. FDA includes many useful tools, but also somechallenges. A functional observation can for example be differentiated, a handy tool not found inthe multivariate tool-box. The speed, and acceleration, can then be calculated from the obtaineddata. How to define "similarity" is, on the other hand, not as obvious as with points. In this work,an FDA-approach is taken on classifying knee kinematic data, from a long-term follow-up studyon knee ligament injuries.This work studies kernel functional classifiers, and k-nearest neighbours models, and performssignificance tests on the model accuracy, using re-sampling methods. Additionally, depending onhow similarity is defined, the models can distinguish different features of the data. Attempts atutilising more information through incorporation of ensemble-methods, does not exceed the singlemodels it is created from. Further, it is shown that classification on optimised sub-domains, canbe superior to classifiers using the full domain, in terms of predictive power. / Främre korsbandsskador är vanliga och välkända skador, speciellt bland idrottsutövare. Skadornakräver ofta operationer och långa rehabiliteringsprogram, och kan leda till funktionell nedsättningoch återskador (Marshall et al., 1977). Målet med det här arbetet är att utforska möjligheten attklassificera knän utifrån funktionalitet, där utfallet är känt. Detta genom att använda olika typerav modeller, och genom att testa olika indelningar av grupper. Datat som används är insamlatunder ett prestandatest, där personer hoppat på ett ben med rörelsesensorer på kroppen. Deninsamlade datan representerar position över tid, och betraktas som funktionell data.Med funktionell dataanalys (FDA) kan en process analyseras som en kontinuerlig funktion av tid,istället för att reduceras till ett ändligt antal datapunkter. FDA innehåller många användbaraverktyg, men även utmaningar. En funktionell observation kan till exempel deriveras, ett händigtverktyg som inte återfinns i den multivariata verktygslådan. Hastigheten och accelerationen kandå beräknas utifrån den insamlade datan. Hur "likhet" är definierat, å andra sidan, är inte likauppenbart som med punkt-data. I det här arbetet används FDA för att klassificera knärörelsedatafrån en långtidsuppföljningsstudie av främre korsbandsskador.I detta arbete studeras både funktionella kärnklassificerare och k-närmsta grannar-metoder, och ut-för signifikanstest av modellträffsäkerheten genom omprovtagning. Vidare kan modellerna urskiljaolika egenskaper i datat, beroende på hur närhet definieras. Ensemblemetoder används i ett försökatt nyttja mer av informationen, men lyckas inte överträffa någon av de enskilda modellerna somutgör ensemblen. Vidare så visas också att klassificering på optimerade deldefinitionsmängder kange en högre förklaringskraft än klassificerare som använder hela definitionsmängden.

京都大学 / 0048 / 新制・課程博士 / 博士(人間健康科学) / 甲第17955号 / 人健博第9号 / 新制||人健||1(附属図書館) / 30785 / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 黒木 裕士, 教授 坪山 直生, 教授 松田 秀一 / 学位規則第4条第1項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM

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