Dans les pathologies ostéo-articulaires, les critères d’évaluation rapportés par les patients (Patient-Reported Outcomes ou PROs) sont désormais les critères de jugement incontournables, réclamés par les autorités sanitaires et les organismes de régulation. La validation de leurs propriétés psychométriques et leur adaptation transculturelle sont donc indispensables pour pouvoir les utiliser dans les essais thérapeutiques internationaux. Ce processus complexe de validation transculturelle permet d’élaborer une version du PRO dans le langage cible qui prenne en considération tous les spécificités socioculturelles et les équivalences linguistiques.Ce travail de thèse a comme problématique la validation transculturelle des PROs spécifiquement développés pour les pathologies du genou et de la hanche. Après avoir explicité les recommandations publiées dans ce domaine puis avoir réalisé une revue de la littérature de la qualité méthodologique des auto-questionnaires disponibles pour ces pathologies articulaires, nous avons entrepris les validations transculturelles du questionnaire KOOS (ou Knee injury and Osteoarthritis Outcome Score), du questionnaire HOOS (ou Hip disability and Osteoarthritis Outcome Score) et de leurs formes réduites (KOOS-PS et HOOS-PS pour Physical function Short form). Ces auto-questionnaires, développés en langue anglaise au cours de la dernière décennie, permettent d’évaluer de manière globale (symptômes, retentissement fonctionnel dans les activités quotidiennes et sportives, qualité de vie) des pathologies du genou ou de la hanche, aussi bien traumatiques que dégénératives. Après traduction et adaptation française selon les recommandations internationales, les versions françaises du KOOS, du HOOS, du KOOS-PS et du HOOS-PS ont ensuite été validées de manière prospective dans des cohortes françaises bi-centriques de patients arthrosiques suivis en milieu rhumatologique et orthopédique. Les résultats de ces travaux, publiés sous la forme de trois articles originaux, démontrent que les propriétés psychométriques des versions françaises de ces questionnaires sont satisfaisantes quelle que soit la sévérité de l’arthrose, en terme de faisabilité, de cohérence interne, de reproductibilité, de validité et de sensibilité au changement (après mise en place de prothèse totale ou viscosupplémentation par acide hyaluronique). Ces PROs capturent des concepts supplémentaires pertinents, comme le retentissement sur les activités sportives ou la qualité de vie, et permettent avec le même outil de mesure le suivi longitudinal de patients, depuis l’atteinte traumatique jusqu’à l’arthrose. Ils améliorent ainsi l’évaluation globale des pathologies du genou et de la hanche. La validation exhaustive, y compris transculturelle, permet à ce jour de considérer les questionnaires KOOS et le HOOS comme des PROS de référence. A ce titre, leur utilisation dans les essais thérapeutiques internationaux doit être encouragée. / In joint diseases, Patient-Reported Outcomes (PROs) are now critical outcome measures, required by health authorities and regulatory agencies. Cross-cultural adaptation and validation of the psychometric properties of such PROs are needed in order to use them in international therapeutic trials. Thanks to this complex process of cross-cultural validation, the PRO in the target language can take into account the specific socio-cultural features and the linguistic equivalences. The aim of this thesis was to undertake the cross-cultural validation of PROs specifically developed for knee and hip disorders. After explaining the published recommendations for cross-cultural adaptation and then conducting a thorough review of reports dealing with the methodological evaluation of self-administered questionnaires in these joint diseases, we carried out the cross-cultural validation of the KOOS questionnaire (Knee injury and Osteoarthritis Outcome Score), the HOOS questionnaire (Hip disability and Osteoarthritis Outcome Score) and their shortened versions (KOOS-PS and HOOS-PS for Physical function Short form). In the last ten years, these self-administered questionnaires were developed in English to assess the patients’ opinion (symptoms, functional disability in activities of daily life or sports activities, quality of life) about their knee and hip problems, both for traumatic and degenerative joint diseases. Following a translation and cross-cultural adaptation in French in accordance with international recommendations, the French versions of the KOOS, HOOS, KOOS-PS and HOO-PS were validated in a bi-centric prospective study of osteoarthritis patients treated in two rheumatology and orthopedics departments. The results of this work, published as three original articles, demonstrate that the psychometric properties of the French versions of these questionnaires are satisfactory in terms of feasibility, internal consistency, reliability, validity and responsiveness (following total hip or knee replacement or intra-articular injection of hyaluronic acid), whatever the degree of severity of osteoarthritis. By capturing additional relevant concepts such as functional disability in sports activities or quality of life and allowing the longitudinal follow-up of patients (from traumatic lesions to osteoarthritis), with the same measurement tool, theses PROs improve the overall assessment of hip and knee disorders. In the light of the exhaustive validation, including cross-cultural adaptation, the KOOS and HOOS questionnaires can now be considered as references PROs in hip and knee disorders and their use in international therapeutic trials should be encouraged.

Abstract Cartilage-related diseases such as osteoarthritis (OA) are a major cause of disability and decrease in the quality of life. Moreover OA causes a heavy economical burden on the social welfare and health care systems. Conventional magnetic resonance imaging (MRI) provides accurate noninvasive method of morphological evaluation of the articular cartilage. However, there are early degenerative changes in the articular cartilage that can be evaluated with modern quantitative MRI methods prior to the signs of cartilage loss. In this study, T2 relaxation time of the articular cartilage was further evaluated in 1.5T in vivo using clinical patients and asymptomatic volunteers. The detection of focal patellar cartilage lesions in T2 mapping as compared to standard clinical MRI was evaluated. T2 mapping showed more lesions than the clinical MRI, and in T2 maps the lesions appeared generally wider. This suggests that T2-mapping is feasible in the clinical setting and may reveal cartilage lesions not seen in the standard knee MRI. The normal topographical variation of T2 relaxation time of articular cartilage in different compartments of the knee joint and at different zones of cartilage in young healthy adults was assessed. T2 values were significantly higher in the superficial zone as compared to the deep tissue at all locations and there was remarkable variation in T2 relaxation between different locations. The normal variation in cartilage T2 within a joint is significant and should be acknowledged when pathology-related T2 changes are investigated. The short- and long-term repeatability of T2 relaxation time measurements of articular cartilage in the knee joint was assessed. The results showed mostly good repeatability, and with careful patient positioning T2 relaxation time at the different cartilage surfaces of the knee can be accurately determined. / Tiivistelmä Nivelrikko, joka usein liittyy nivelruston vaurioitumiseen, aiheuttaa merkittävää toimintakyvyn ja elämänlaadun heikentymistä ikääntyvässä väestössä. Lisäksi nivelrikosta aiheutuu merkittäviä kustannuksia sosiaali- ja terveydenhuollolle. Magneettikuvaus on tarkka kajoamaton menetelmä rustovaurioiden arvioimiseksi. Kuitenkin rustovaurion alkuvaiheessa tapahtuu ruston sisäisiä rakenteellisia ja biokemiallisia muutoksia, joita on mahdollista arvioida uusilla kvantitatiivisilla magneettikuvausmenetelmillä ennen varsinaisten rustopuutosten kehittymistä. Tässä tutkimuksessa tutkittiin ruston T2-relaksaatioaikamittausta 1.5T magneettikuvauslaitteella sekä potilasaineistossa että vapaaehtoisilla. Tutkimuksessa verrattiin paikallisten rustomuutosten havaitsemisen herk¬kyyttä T2-relaksaatioaikakartoituksen ja tavanomaisen kliinisen magneetti¬kuvauksen välillä kliinisessä potilasaineistossa. T2-relaksaatiomittaus osoitti useampia muutoksia kuin kliininen magneettikuvaus ja muutokset olivat yleensä laajempia. Voidaan olettaa, että T2-relaksaatioaikamittaus soveltuu kliiniseen käyttöön ja voi osoittaa tavanomaisessa magneettikuvauksessa näkymättömiä rustomuutoksia. Tutkimuksessa arvioitiin ruston T2-relaksaatioajan paikkakohtaista ja kerroksittaista vaihtelua polven nivelpintojen eri alueilla nuorten vapaaehtoisten aineistossa. T2-relaksaatioaika oli merkitsevästi pidempi ruston pinnallisessa kuin syvässä kerroksessa kaikilla nivelpintojen alueilla. Lisäksi T2-relaksaatioajassa oli merkittävää normaalia vaihtelua eri alueiden välillä ja tämä tulisi huomioida ruston patologisia muutoksia arvioitaessa. Tutkimuksessa arvioitiin polven ruston T2-relaksaatioajan lyhyen ja pitkän aikavälin toistettavuutta vapaaehtoisaineistossa. Tulokset osoittivat enimmäkseen hyvää toistettavuutta ja huolellisella asettelulla voidaan ruston T2-relaksaatioaika mitata luotettavasti polven nivelpintojen eri alueilla.

Abstract The work describes the design, construction and commissioning of the underground cosmic-ray experiment Experiment with MultiMuon Array (EMMA). The experiment is built into the Pyhäsalmi mine, in the town of Pyhäjärvi, Finland. The aim of EMMA is to determine the elemental composition of cosmic rays at an energy region around 4 PeV, the energy region called the ’knee’ region. This is achieved by measuring the lateral density distribution of high-energy muons originating from Extensive Air Showers (EAS). The design calculations for the EMMA experiment, which are based on the use of the parametrization of the lateral density distribution of muons, the method of shower reconstruction, and the energy and composition indicators, are presented. A strategy for reconstructing the composition of the cosmic rays is presented and it demonstrates the potential of applying unfolding techniques to the EMMA data. The effect of an array extension on the performance of EMMA is studied. The hardware used in the EMMA experiment is presented starting with an overview of the array and its detector stations. The EMMA array employs three different particle detectors, for which the main technical properties are given, and their use in the EMMA array is presented. A description of the infrastructure of the experiment is given and the rock overburden at the EMMA site at the depth of 80 metres is documented. The work contains the latest analysis of EAS data recorded by the tracking detectors of the experiment, which demonstrates that the experiment is taking data as planned and that the data are according to EAS physics expectations. Methods for event selection and tracking efficiency correction are presented, after which the analysis results of measured track multiplicity spectra are given. The shape of the recorded multiplicity spectrum indicates that the simplest model of a knee-like spectrum with a pure proton composition can not explain the data and that further analysis of the spectrum is required.

No description available.

La cryothérapie est utilisée de manière large et empirique à visée adjuvante dans les rhumatismes inflammatoires, avec un niveau de preuve faible. Dans une revue systématique de la littérature, en poolant les données de 6 études non contrôlées, nous avons pu démontrer que la cryothérapie (locale ou corps entier) appliquée deux fois par jour pendant 7 à 15 jours réduisait significativement l'EVA douleur et le score d'activité DAS25 dans la polyarthrite rhumatoïde. La cryothérapie locale (glace ou gaz froide) montrait par ailleurs des effets taille intra-classes supérieurs à ceux obtenus en utilisant la cryothérapie corps entier. L'objectif de ce travail était de mesurer les effets de la cryothérapie locale sur al douleur, l'inflammation synoviale et systémique chez les patients arthritiques et dans le modèle murin d'arthrite à l'adjuvant. Dans les études randomisées CDRI et ALGGAR, nous avons évalué les effets de deux applications locales de froid (glace versus gaz froid) sur la douleur, l'activité Doppler et les taux protéiques de cytokines intra-articulaires controlatéraux non souffrant d'arthrites de genou non septiques. Les genoux arthritiques controlatéraux non traités étaient utilisés comme contrôles. Nous avons par ailleurs étudié in vitro les effets de l'hypothermie modérée (30°C pendant 2heures) sur l'expression protéique des cytokines dans un modèle de culture de rotules de rats arthritiques. Nous avons enfin étudié in vitro dans l'arthrite à l'adjuvant les effets de l'application sub-chronique de glace ou de gaz froid (2 fois par jour pendant 14 jours versus contrôles arthritiques non traités) sur le score d'arthrite, le diamètre de cheville, la transcription des gènes codant pour les cytokines pro-inflammatoires dans les pattes arrières (Q-RT-PCR) et l'expression protéique des cytokines dans le plasma (Multiplex et ELISA) après 14 jours de traitement. Dans l'étude CDRI, la cryothérapie locale (glace et gaz froid) réduisait significativement l'EVA douleur ainsi que le score Doppler dans les genoux traités, ces effets persistant le lendemain des deux applications. Dans une analyse intermédiaire des résultats de l'étude ALGGAR, en combinant les deux groupes de traitement (glace et gaz de froid), nous avons observé une baisse des taux d'IL-6, d'IL-1β et de VEGF dans le liquide articulaire arès deux applications. dans les cultures d'explants de rotules de rats arthritiques, l'hypothermie ponctuelle réduisait significativement les taux d'IL-6, IL-17A et IL-1β dans les pattes arrières après 14 jours de traitement. Les deux modalités réduisaient significativement les niveaux plasmatiques d'IL-17A et la glace réduisait en outre les taux d'IL-6 et de VEGF. Nous n'avons observé aucun effet de la cryothérapie locale sur le voie du TNF-α chez l'homme ni chez l'animal. Nos résultats démontrent pour la première fois un effet thérapeutique et anti-inflammatoire de la cryothérapie locale dans l'arthrite. Les effets biologiques était IL-6/IL-147 dépendants et TNF-α indépendants. Des études complémentaires permettront de mieux caractériser les mécanismes moléculaires sous-jacents et de déterminer su la cryothérapie locale pourrait être une alternative aux AINS et corticoïdes dans les rhumatismes inflammatoires. / Cryotheapy i widely and empirically used in an adjuvant setting in inflammatory rheumatic diseases, with a low level of evidence. We performed a systematic review of the literature and, by pooling data from 6 non-controlled studies, we could show that local cryotherapy (local or whole-body cryotherapy) applaied twice a day for 7-15 days significantly reduced the pain VAS and the DAS28 activity score in rheumatoid arthritis. Furthermore, local cryotherapy (ice packs or cold gas) showed significantly greater intra)class effect-sizes compared to whole-body cryotherapy. The aim of this work was to measure the effects of local cryotherapy on pain, synovial and systemic inflammation in arthrici patients and in the murine model of adjuvant-induced arthritis. First, in the CDRI and ALGGAR randomized studies, we evaluated the effects of 2 local cold applications (ice versus cold gas) on pain, power Doppler activity and intra-joint cytokine protein levels in 46 patients suffering from non-septic knee arthritides. Contralateral arthritic knee were used as control. Secondly, we studied the in vitro effects of mild hypothermia (30°C for 2 hours) on cytokine protein expression in a model of cultured arthritic rat patellae. Thidly, we studied the in vitro effects of sub-chronically applied ice or cold gas (twice a day for 14 days versus non-treated arthritic controls) on the arthritis score, the ankle diameter, pro-inflammatory cytokine gene transcription levelsin hind paws (Q-RT-PCR) and cytokine plasma protein levelx (Multiplex and ELISA) after 14 days of treatment. In the CDRI study, local cryotherapy (ice and cold gas) significantly reduced the pain VAS and the power Doppler score in treated kness, and these effects remained significant the day afetr 2 cold applicaitions. In an intermediate analysis of the ALGGAR study results, by pooling the 2 treatment groups, we could show significant decreases in IL-6 protein, IL-1β and VEGF synovial fluid protein levels after 2 cold applicatios. In arthritic rat patella explangt culture experiments, punctual hypothermia significantly reduced IL-6 protein levels. In vivon ice was more efficient on the clinical parameters and better tolerated compared to cold gas. Both techniques significantly reduced IL-6, IL-17A ans IL-1β gene transcription levels in hind paws after 14 days of treatment. Both techniques redcued IL-17A plasma protein levles, while ice also reduced IL-6 and VEGF plasma protein levels. Conversely, we observed no effect of local cryotherapy on the TNF-α pathway, neither in patients nor in our animal model. Here we demonstrate for the first time therapeutic and anti-inflammatory effet-cts of local cryothepary in arthritis. The biological effects were IL-6/IL-17-driven and TNF-α independent. Further studies will help elucidate the underlying molecular mlechanisms involved and detemrine whether local cryotherapy might be a safer alternative to NSAIDs ans corticosteroids in inflammatory rheumatic diseases.

No description available.

Ground reaction force (GRF) data collected and synchronized with film data to determine peak GRF and calculate moments about ankle and knee during rope skipping. Two, five minute conditions were analyzed for 10 subjects. Condition 1 was set rate and style. Condition 2 was subjects' own rate and style. Means and standard deviations were reported for peak GRF, ankle and knee moments. One way ANOVAs reported no significant difference between conditions for variables measured. Efficiency and nature of well phased impacts during rope skipping may be determined by combination of GRF, similarities in magnitude and direction of joint moments, and sequencing of segmental movements. Technique and even distribution of force across articulations appear more important than magnitudes of force produced by given styles.

abstract: Robotic lower limb prostheses provide new opportunities to help transfemoral amputees regain mobility. However, their application is impeded by that the impedance control parameters need to be tuned and optimized manually by prosthetists for each individual user in different task environments. Reinforcement learning (RL) is capable of automatically learning from interacting with the environment. It becomes a natural candidate to replace human prosthetists to customize the control parameters. However, neither traditional RL approaches nor the popular deep RL approaches are readily suitable for learning with limited number of samples and samples with large variations. This dissertation aims to explore new RL based adaptive solutions that are data-efficient for controlling robotic prostheses. This dissertation begins by proposing a new flexible policy iteration (FPI) framework. To improve sample efficiency, FPI can utilize either on-policy or off-policy learning strategy, can learn from either online or offline data, and can even adopt exiting knowledge of an external critic. Approximate convergence to Bellman optimal solutions are guaranteed under mild conditions. Simulation studies validated that FPI was data efficient compared to several established RL methods. Furthermore, a simplified version of FPI was implemented to learn from offline data, and then the learned policy was successfully tested for tuning the control parameters online on a human subject. Next, the dissertation discusses RL control with information transfer (RL-IT), or knowledge-guided RL (KG-RL), which is motivated to benefit from transferring knowledge acquired from one subject to another. To explore its feasibility, knowledge was extracted from data measurements of able-bodied (AB) subjects, and transferred to guide Q-learning control for an amputee in OpenSim simulations. This result again demonstrated that data and time efficiency were improved using previous knowledge. While the present study is new and promising, there are still many open questions to be addressed in future research. To account for human adaption, the learning control objective function may be designed to incorporate human-prosthesis performance feedback such as symmetry, user comfort level and satisfaction, and user energy consumption. To make the RL based control parameter tuning practical in real life, it should be further developed and tested in different use environments, such as from level ground walking to stair ascending or descending, and from walking to running. / Dissertation/Thesis / Doctoral Dissertation Electrical Engineering 2020

Evolution had played a significant role in structuring on how humans stand, walk or run. The nervous system plays a major role in the control of locomotion and injuries to the system can lead to gait abnormalities or disabilities. A Spinal Cord Injury (SCI) causes lack of signal communication between the central nervous system and the muscle fibers leading to deprived or no activation of the muscles thus resulting in paraplegia or quadriplegia. Over the past decade wearable robotics and exoskeletons have been gaining outstanding recognition in the field of medical, assistive and augmentative robotics and have led to numerous new innovative mechanisms in the mechanical engineering field. Due to fast paced research activities, the critical importance and performance of mechanisms such as wrap spring clutch/brake,Wafer Disc brakes are overlooked or used ineffectively. So, researchers tend to create new actuators from scratch and have limited their use of previously available resources, which has prevented us to explore the potential of these devices.The research presented focuses on developing a mechanism (“A Wrap Spring Clutch/Brake Mechanism”) from scratch using a trade study approach. This thesis addresses the fundamental relationship between coefficient of friction, interference, spring diameter and the holding torque of the mechanism using analytical, testing and simulation results. The human biomechanical data during ground level walking was used as design targets to develop the mathematical model of the system. Data from the testing stated that these targeted goals have been achieved by the design. This mechanism is used as a Knee Joint for the Hybrid EXoskeleton (HEX) GEN-1 project which is developed at the Automation and Interventional Medicine (AIM) Robotics Research Laboratory to rehabilitate the SCI.

INTER-SEGMENT COORDINATION VARIABILITY POST ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION SEPTEMBER 2015 DEVIN K. KELLY, B.S., UNIVERSITY OF MASSACHUSETTS AMHERST M.S., UNIVERSITY OF MASSACHUSETTS AMHERST Directed by: Dr. Joseph Hamill There is an increased risk for ipsilateral graft rupture and contralateral ACL rupture following ACL reconstruction surgery (ACLR) despite return to sport clearance. The reason for this increased risk is not well understood. Previous literature has shown that decreased coordination variability is indicative of an injured system regardless of the absence of pain. PURPOSE: To quantify inter-segment coordination variability during three portions of the stance phase of gait in athletes at three progressive time points post-surgery compared to the contralateral limb (NI) and healthy controls. METHODS: Three-dimensional kinematic and kinetic data were collected for 10 ACLR and 10 healthy athletes matched for age, gender, and activity level. The ACLR group was measured at 4 weeks, 12 weeks, and when cleared to run post-surgery. Kinematic data were used in a modified vector coding technique to determine inter-segment coordination variability of lower extremity couples of interest. Statistical significance was determined using two factor multivariate ANOVAs (limb x visit) for early (1-33%), mid (34-66%), and late (67-100%) stance with alpha level set at .05. Tukey post-hoc tests were performed where appropriate. RESULTS: ACLR athletes have decreased inter-segment coordination variability of the involved lower extremity during the late stance phase of gait compared to both the contralateral limb and healthy controls at 4 weeks post-surgery. By 12 weeks post-surgery there were improvements in joint function as exemplified by inter-segment coordination variability of the ACLR involved limb becoming similar to the healthy control limb. CONCLUSION: Inter-segment coordination variability during late stance in the present study is not an indication for the increased risk for ipsilateral graft rupture and contralateral ACL rupture in ACLR athletes.