Yes / /Aims: Partial weight-bearing protocols are commonly incorporated into hospital, clinical and field-based rehabilitation to enhance recovery, particularly in patients following cartilage surgeries. Overloading can affect healing time and the stability or integrity of the healing structure, however underloading can also be detrimental, as adequate weight bearing encourages the healing process—for example, osteoblastic stimulation. Therefore, accurate reproducibility of these protocols could be considered essential to the rehabilitation process. The aim of this study was to determine the accuracy with which weight-bearing protocols (20%, 50% or 80% of body weight) could be reproduced shortly after being taught. Methods: Thirty participants were taught three partial weight-bearing protocols (20%, 50% and 80% of body weight), using bathroom scales. Participants ability to reproduce their target load for each protocol was assessed statically using bathroom scales and dynamically with a force plate using a three-point elbow crutch-assisted gait. Participants were assessed 10 minutes after being taught. Errors between actual and target load during these trials was calculated. Findings: Accuracy assessed with scales was comparatively good for all target loads, however dynamic trials using the force plate showed an inverse relationship between all error measures and target loads (i.e. 20% > 50% > 80% body weight; all P<0.01). The peak error was double the intended load at 20% of body weight (95% CI: 11.9% body weight, 24.1% body weight). At 80% of body weight, the peak error was not significantly different from zero. Conclusions: The static method of instruction of partial weight-bearing protocols, using bathroom scales, does not seem to translate accurately to dynamic motion, and therefore affects adherence to medical instruction. Practitioners should be aware of the potential errors in reproducing these loads and the potential effect on rehabilitation. These results would suggest that practitioners should be cautious when using bathroom scales to teach partial weight-bearing protocols and not to rely on them to assess reproduction accuracy during gait

Yes / Partial weight bearing protocols are commonly incorporated into rehabilitation to enhance recovery. Patients are often prescribed protocols that refer to a percentage of their body weight, such as 20% weight bearing, that should be placed through the healing limb during activities such as walking (gait). In order to achieve these partial weight baring protocols patients are usually provided with walking aids such as crutches. Accurate reproducibility of and compliance with these protocols could be considered essential to the rehabilitation process, however poor reproducibility of partial weight bearing protocols during crutch assisted gait using a current method of instruction has been shown. Aims: The aim of this study was to determine whether a more dynamic method of partial weight bearing protocol instruction, was more accurately reproduced. Methods: In total, 16 participants were randomly allocated to one of two groups and were taught 20% partial weight bearing using two different methods of instruction. A participant’s ability to reproduce their target load using crutch assisted gait was assessed using a force plate. Findings: The mean error for the static method of instruction was significantly greater than the more dynamic method. Conclusion: As seen previously, the static method of instruction of partial weight bearing protocols, using bathroom scales, does not seem to translate accurately to dynamic motion; however, the more dynamic method assessed in this study appears to result in more accurate reproducibility.

L’asymétrie de mise en charge (MEC) lors du passage assis à debout (PAD) chez les personnes hémiparétiques est une observation clinique connue mais peu expliquée. Ce projet visait donc le développement de connaissances sur les facteurs explicatifs de l’asymétrie de MEC chez cette clientèle en s’intéressant plus spécifiquement au lien entre la distribution des efforts aux genoux lors du PAD et l’asymétrie de MEC observée ainsi qu’à la perception de ces deux éléments lors de cette tâche. Ainsi, les objectifs généraux étaient de : 1) déterminer si l’exécution spontanée asymétrique du PAD des sujets hémiparétiques est expliquée par une distribution des efforts symétriques aux genoux en quantifiant ces efforts par le Taux d’utilisation musculaire électromyographique (TUMEMG) et, 2) déterminer si les individus hémiparétiques sont conscients des stratégies motrices qu’ils utilisent en évaluant leurs perceptions de MEC et d’efforts aux genoux durant le PAD. La première étude a évalué la capacité des personnes hémiparétiques à percevoir leur distribution de MEC aux membres inférieurs lors du PAD. Par rapport aux participants sains, leur distribution de MEC fut davantage asymétrique et leurs erreurs de perception plus élevées. La deuxième étude a quantifié la distribution des efforts aux genoux chez les sujets sains et hémiparétiques lors du PAD spontané. Les deux groupes ont montré une association entre leur distribution de MEC et leur distribution d’effort. Toutefois, la relation était plus faible chez les patients. Le classement des participants hémiparétiques en sous-groupes selon leur degré d’asymétrie de force maximale des extenseurs des genoux (faible, modéré, sévère) a révélé une similarité des efforts aux genoux parétique et non parétique chez le groupe ayant une atteinte sévère. La troisième étude a déterminé si la perception de la distribution des efforts aux genoux des sujets hémiparétiques était reliée à leur distribution réelle d’effort mesurée lors de PAD exécutés dans différentes positions de pieds. En plus d’être incapables de percevoir les changements de distribution d’effort induits par les différentes positions de pieds, leurs erreurs de perception d’effort furent plus élevées que celles de MEC. Par le biais du test fonctionnel assis-debout de cinq répétitions, la dernière étude a déterminé l’influence du nombre de répétitions du PAD sur les distributions de MEC et d’efforts aux genoux chez les sujets sains et hémiparétiques. Contrairement aux contrôles, les distributions des sujets hémiparétiques furent plus asymétriques à la première répétition du test fonctionnel que lors de l’exécution spontanée unique du PAD. En somme, les résultats de cette thèse ont démontré que la distribution des efforts aux genoux doit être considérée parmi les facteurs explicatifs de l’asymétrie de MEC des individus hémiparétiques lors du PAD et qu’il y a un besoin de mieux documenter la perception des personnes hémiparétiques lorsqu’elles exécutent des tâches fonctionnelles. / Weight-bearing (WB) asymmetry during sit-to-stand (STS) in hemiparetic individuals is frequently observed in clinical practice but it has never been well explained. The aim of this project, therefore, was to develop our knowledge of the factors accounting for the WB asymmetry in this population by focusing more specifically on the relationship between the knee effort distribution during the STS task and the WB asymmetry observed as well as on the perception of these two elements during this task. Thus, the general objectives were to: 1) determine whether the spontaneous asymmetrical execution of the STS task in hemiparetic subjects can be explained by a symmetrical distribution of the efforts at the knees by quantifying these efforts using the Electromyographic Muscular Utilization Ratio (EMUR) and, 2) determine whether these hemiparetic individuals are aware of their motor strategies by evaluating their perception of both knee effort and WB distributions during the STS task. The first study evaluated the capacity of hemiparetic persons to perceive their WB distribution at their lower limbs during the STS task. Compared to the healthy participants, their WB distribution was more asymmetrical and they showed greater errors in perception. The second study quantified the distribution of efforts at the knees among healthy and hemiparetic subjects during a spontaneous STS task. Both groups showed an association between their WB distribution and their distribution of efforts but the relationship was not as strong in the hemiparetic group. Dividing the hemiparetic participants into subgroups, according to their knee extensors’ strength asymmetries (mild, moderate, severe), revealed symmetrical knee efforts between sides for the severe group. The third study determined whether hemiparetic individuals’ perception of their knee effort distribution was related to their real distribution of efforts measured during STS tasks performed in various foot positions. Not only were they unable to perceive the changes in the distribution of effort induced by the different foot positions but their errors in perception of effort were greater than in WB. With the use of the five-repetition sit-to-stand test, the last study determined the influence of the number of repetitions of the STS on the distributions of WB and effort at the knees among healthy and hemiparetic subjects. Unlike the controls, the distributions of the hemiparetic subjects were more asymmetrical at the first repetition of the functional test than in the single spontaneous execution of the STS. To summarize, the results of this thesis showed that the distribution of efforts at the knees should be considered among other factors explaining the WB asymmetry of hemiparetic individuals during STS and that there is a need to better document the perception of hemiparetic persons when they execute functional tasks.

Lau Tsz Chung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (leaves 57-66). / Text in English; abstracts in English and Chinese. / Lau Tsz Chung. / Acknowledgement --- p.i / Abstract --- p.ii / Table of contents --- p.v / List of Figures --- p.viii / List of Tables --- p.x / Introduction --- p.1 / Background --- p.1 / Statement of Problem --- p.3 / Research Question --- p.4 / Significance of the Study --- p.4 / Theoretical Contribution --- p.4 / Practical Contribution --- p.5 / Review of Literature --- p.7 / Load carrying on Level Ground --- p.7 / Research Method Involved --- p.8 / Modified Gait Pattern During Load Carriage --- p.9 / Trunk Posture --- p.10 / Low Back Pain --- p.11 / Posture and Back Pain --- p.12 / Load Carrying Studies in Children --- p.14 / Stair Walking --- p.15 / Compared with Level Walking --- p.15 / Temporal Characteristics --- p.17 / Kinematics Measurement --- p.18 / Stair Dimensions --- p.19 / Stair Walking with Load Carriage --- p.21 / Physiological Studies --- p.21 / Biomechanical Studies --- p.21 / Methodology --- p.24 / Design --- p.24 / Subject --- p.24 / Instrumentation --- p.25 / Motion Analysis System --- p.25 / School Bag --- p.25 / Experimental Set-up --- p.25 / Procedure --- p.26 / Term Definition --- p.27 / Data Analysis --- p.27 / Results --- p.29 / Ascending Stair --- p.29 / Posture --- p.29 / Effect on Load Weight --- p.29 / Effect on Load Carrying Method --- p.30 / Velocity --- p.30 / Parameters of Lower Extremities --- p.30 / Descending Stair --- p.31 / Posture --- p.31 / Effect on Load Weight --- p.31 / Effect on Load Carrying Method --- p.31 / Velocity --- p.32 / Parameters of Lower Extremities --- p.32 / Trend --- p.32 / Summary --- p.33 / Discussion --- p.35 / Ascending Stair --- p.35 / Posture --- p.35 / Different Load Weights --- p.35 / Different Carrying Methods --- p.39 / Velocity --- p.40 / Descending Stair --- p.42 / Posture --- p.42 / Velocity --- p.46 / Parameters of Lower Extremities --- p.47 / Trend --- p.48 / Back Pain --- p.49 / Recommended Carrying Load Method and Weight for Children --- p.50 / Limitations of the Study --- p.52 / Further Study --- p.53 / Conclusion --- p.56 / References --- p.57 / Appendix --- p.67 / Appendix A - The experimental Set-up --- p.67 / Appendix B - Subject Consent Form --- p.68 / Appendix C - Figures and Tables --- p.71

L’asymétrie de mise en charge (MEC) lors du passage assis à debout (PAD) chez les personnes hémiparétiques est une observation clinique connue mais peu expliquée. Ce projet visait donc le développement de connaissances sur les facteurs explicatifs de l’asymétrie de MEC chez cette clientèle en s’intéressant plus spécifiquement au lien entre la distribution des efforts aux genoux lors du PAD et l’asymétrie de MEC observée ainsi qu’à la perception de ces deux éléments lors de cette tâche. Ainsi, les objectifs généraux étaient de : 1) déterminer si l’exécution spontanée asymétrique du PAD des sujets hémiparétiques est expliquée par une distribution des efforts symétriques aux genoux en quantifiant ces efforts par le Taux d’utilisation musculaire électromyographique (TUMEMG) et, 2) déterminer si les individus hémiparétiques sont conscients des stratégies motrices qu’ils utilisent en évaluant leurs perceptions de MEC et d’efforts aux genoux durant le PAD. La première étude a évalué la capacité des personnes hémiparétiques à percevoir leur distribution de MEC aux membres inférieurs lors du PAD. Par rapport aux participants sains, leur distribution de MEC fut davantage asymétrique et leurs erreurs de perception plus élevées. La deuxième étude a quantifié la distribution des efforts aux genoux chez les sujets sains et hémiparétiques lors du PAD spontané. Les deux groupes ont montré une association entre leur distribution de MEC et leur distribution d’effort. Toutefois, la relation était plus faible chez les patients. Le classement des participants hémiparétiques en sous-groupes selon leur degré d’asymétrie de force maximale des extenseurs des genoux (faible, modéré, sévère) a révélé une similarité des efforts aux genoux parétique et non parétique chez le groupe ayant une atteinte sévère. La troisième étude a déterminé si la perception de la distribution des efforts aux genoux des sujets hémiparétiques était reliée à leur distribution réelle d’effort mesurée lors de PAD exécutés dans différentes positions de pieds. En plus d’être incapables de percevoir les changements de distribution d’effort induits par les différentes positions de pieds, leurs erreurs de perception d’effort furent plus élevées que celles de MEC. Par le biais du test fonctionnel assis-debout de cinq répétitions, la dernière étude a déterminé l’influence du nombre de répétitions du PAD sur les distributions de MEC et d’efforts aux genoux chez les sujets sains et hémiparétiques. Contrairement aux contrôles, les distributions des sujets hémiparétiques furent plus asymétriques à la première répétition du test fonctionnel que lors de l’exécution spontanée unique du PAD. En somme, les résultats de cette thèse ont démontré que la distribution des efforts aux genoux doit être considérée parmi les facteurs explicatifs de l’asymétrie de MEC des individus hémiparétiques lors du PAD et qu’il y a un besoin de mieux documenter la perception des personnes hémiparétiques lorsqu’elles exécutent des tâches fonctionnelles. / Weight-bearing (WB) asymmetry during sit-to-stand (STS) in hemiparetic individuals is frequently observed in clinical practice but it has never been well explained. The aim of this project, therefore, was to develop our knowledge of the factors accounting for the WB asymmetry in this population by focusing more specifically on the relationship between the knee effort distribution during the STS task and the WB asymmetry observed as well as on the perception of these two elements during this task. Thus, the general objectives were to: 1) determine whether the spontaneous asymmetrical execution of the STS task in hemiparetic subjects can be explained by a symmetrical distribution of the efforts at the knees by quantifying these efforts using the Electromyographic Muscular Utilization Ratio (EMUR) and, 2) determine whether these hemiparetic individuals are aware of their motor strategies by evaluating their perception of both knee effort and WB distributions during the STS task. The first study evaluated the capacity of hemiparetic persons to perceive their WB distribution at their lower limbs during the STS task. Compared to the healthy participants, their WB distribution was more asymmetrical and they showed greater errors in perception. The second study quantified the distribution of efforts at the knees among healthy and hemiparetic subjects during a spontaneous STS task. Both groups showed an association between their WB distribution and their distribution of efforts but the relationship was not as strong in the hemiparetic group. Dividing the hemiparetic participants into subgroups, according to their knee extensors’ strength asymmetries (mild, moderate, severe), revealed symmetrical knee efforts between sides for the severe group. The third study determined whether hemiparetic individuals’ perception of their knee effort distribution was related to their real distribution of efforts measured during STS tasks performed in various foot positions. Not only were they unable to perceive the changes in the distribution of effort induced by the different foot positions but their errors in perception of effort were greater than in WB. With the use of the five-repetition sit-to-stand test, the last study determined the influence of the number of repetitions of the STS on the distributions of WB and effort at the knees among healthy and hemiparetic subjects. Unlike the controls, the distributions of the hemiparetic subjects were more asymmetrical at the first repetition of the functional test than in the single spontaneous execution of the STS. To summarize, the results of this thesis showed that the distribution of efforts at the knees should be considered among other factors explaining the WB asymmetry of hemiparetic individuals during STS and that there is a need to better document the perception of hemiparetic persons when they execute functional tasks.

Low trauma hip fractures, due to bone fragility, are a major healthcare burden with serious consequences for individuals in terms of long-term morbidity and mortality; and also for society due to the high medical and care costs associated with these injuries. Because of the association with low bone mass, these fractures are particularly prevalent in elderly populations and are likely to become more common as longevity increases globally. Avoidance of these fractures is therefore an extremely important goal. Low bone mass, manifested in the conditions of osteopenia and osteoporosis, is the primary cause of bone fragility, and reductions in bone mass are the inevitable corollary of aging and menopause. Bone loss may be exacerbated by immobilisation and reduced weight-bearing activity, giving rise to the condition of disuse osteopenia. Immobilisation may itself be the result of low trauma leg fragility fractures that potentially causes further bone density loss. If this loss occurs at the hip, there is an increased risk for hip fracture as a sequela to the original injury. Osteoarthritis is also a condition strongly associated with aging that may necessitate knee arthroplasty as a last stage treatment, potentially causing a period of reduced mobility and weight-bearing activity following surgery. Leg fracture and knee replacement both present additional risk factors for hip fracture due to changes in muscle mass, gait and postural stability that may increase the risk of falls. This study aims primarily to investigate the effects of immobilisation on leg fracture and knee replacement patients, immediately following injury or surgery, in order to quantify bone and muscle loss and to monitor recovery over a one year period. A postmenopausal population were studied as they are already losing bone density systemically and may be at greater risk of further bone loss following immobilisation. Factors of activity, function, weight-bearing, pain, treatments, therapies, health perceptions and mental wellbeing, that potentially contribute to bone loss and recovery, were also investigated. Results from the study may provide information relating to increased future hip fracture risk and lead to treatment options to alleviate bone loss in these groups.

A broad understanding of motor control has been achieved through research performed on upper extremity reaching, walking on level ground, and static balance. Though invaluable insights have been achieved under these testing paradigms, inherent limitations result in less being known regarding functional movement in weight-bearing. Gait studies require large numbers of consecutive steps to achieve high reliability, static balance is limited to the goal of no movement, and upper extremity reaching lacks insights into feedback from the vestibular system. Here we describe (and provide a supplemental video of) a system for testing and training the performance of a weight-bearing, visuomotor task in the form of a mini-squat according to a sinusoidal trace on a screen. In this work, we determined that by altering both task movement rate and resistance at the knee, a hierarchy of difficulty was achieved at all ages. As age increases, there is a velocity-error tradeoff; speed of movement is attempted to be maintained while error is sacrifieced. When introducing an unexpected force perturbation (rapid release of the resistance of the squat for less than a second), older adults who are least able to match the frequency of the task experience the greatest error and velocity rates during the perturbation. This exposes a possible deficit in the feedback control system of even healthy older adults, where future studies may determine if early intervention to prevent such changes may prevent future injury and disability. When older and younger adults learned to perform the visuomotor task while performing a simultaneous cognitive task, learning was slowed as complexity of the cognitive task increased. In older adults, a difficult cognitive task inhibited acquisition of the squatting task with no apparent improvement in trial error nor coherence. Upon retesting of the motor task, there was no difference between dual-task and single-task trained ability to consolidate the motor task in both age groups, though those that trained under a dual-task condition were more able to automate the motor task as measured by a smaller dual-task cost. This may indicate that dual-task training leads to freeing cognitive resources from attending to a functional movement so that they may attend to other tasks such as what may be happening in the environment. Finally, executive function as measured by the Flanker Test, explained 80% of the variability of final day visuomotor error, being a possible prognostic factor for dual-task interventions. Future directions will determine if increased automaticity of a mini-squat will lead improvement to overall improved functional mobility and reduced lower extremity injuries when functioning in a busy community.

Diss. (sammanfattning) Umeå : Umeå universitet, 2009. / Härtill 4 uppsatser. Även tryckt utgåva.

Made available in DSpace on 2014-12-17T15:16:17Z (GMT). No. of bitstreams: 1 CamilaRS_DISSERT.pdf: 2859440 bytes, checksum: 300f17e45e74e1c8156a1d4dc7707bf9 (MD5) Previous issue date: 2012-12-18 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / A adi??o de carga aos membros inferiores durante a marcha ? uma perturba??o capaz de promover mudan?as adaptativas no padr?o locomotor de crian?as e adultos saud?veis ou com patologias neurol?gicas. Os efeitos desta perturba??o sobre a marcha de crian?as com paralisia cerebral hemipar?tica esp?stica (PCHE) ainda n?o foram investigados. OBJETIVO: Avaliar os efeitos imediatos do treino na esteira com adi??o de carga aos membros inferiores, sobre os par?metros cinem?ticos da marcha de crian?as com PCHE. MATERIAIS E M?TODOS: Foi realizado um estudo quase-experimental. Participaram do estudo 20 crian?as com PCHE, de ambos os sexos, com m?dia de idade de 8,8?2,39 anos. Todos os sujeitos foram classificados quanto ao seu n?vel de funcionalidade (GMFCS - Sistema de Classifica??o da Fun??o Motora Grossa) e quanto ? fun??o motora grossa (GMFM - Gross Motor Function Measure), n?vel socioecon?mico (Crit?rio Classifica??o Econ?mica Brasil), grau de espasticidade muscular (Escala Modificada de Ashworth), medidas antropom?tricas, al?m da avalia??o dos par?metros cinem?ticos da marcha atrav?s do sistema Qualisys. As crian?as realizaram treino na esteira com carga nos tornozelos, em uma ?nica sess?o. Foram avaliados os par?metros cinem?ticos em tr?s fases: Antes do treinamento (FPR?); Imediatamente ap?s o treino (FP?S); e 5 minutos ap?s o t?rmino do treino (FRET). Os resultados foram analisados pelo SPSS 17.0, atribuindo-se n?vel de signific?ncia de 0,05. Para compara??o das tr?s fases avaliadas, foi realizado o teste ANOVA one way para medidas repetidas. O teste de Bonferroni foi aplicado para identificar a diferen?a entre as vari?veis. RESULTADOS: Foi observado aumento estatisticamente significativo na altura do deslocamento do p?, amplitude de movimento e flex?o m?xima do quadril e joelho na fase de balan?o, quando se comparou as fases FPR? x FP?S e FP?S x FRET. As vari?veis espa?o temporais n?o apresentaram diferen?a estat?stica entre as condi??es. CONCLUS?O: O treino de marcha na esteira com adi??o de carga aos membros inferiores se apresentou como uma perturba??o capaz de modificar a estrat?gia locomotora de crian?as com PCHE

This thesis is based on studies of the ten-year community-based intervention programme entitled, the Vadstena Osteoporosis Prevention Project (VOPP). The specific aims of the research were to describe the effects of physical activity and training programmes on bone mass and balance performance in adults, to determine whether a fall risk prevention programme could motivate personal actions among the elderly, to ascertain whether the intervention programme could reduce the incidence of forearm and hip fractures. Two studies addressed training programmes for middle-aged and old people. First, VOPP participants who were aged 40–70 years and had low forearm bone mineral density (BMD) values were invited to take part in a one-year weight-bearing training study. Thirty of those individuals were included in the investigation. Additional bone mass measurements were performed at the hip and the lumbar spine, and balance and aerobic capacity were also tested. The training programme was performed twice a week (I). In the second study, healthy persons aged 70–75 years were invited to participate in a balance-training study. Fifteen persons joined an exercise group, and another fifteen were controls. The training programme comprised specific balance exercises and was carried out twice a week for nine weeks (II). The association between forearm BMD values and several lifestyle factors was explored in random samples of the population aged 20–72 years (n=880) in a cross-sectional study (III). Another study explored the association between calcaneal stiffness, forearm BMD, and lifestyle factors amongst participants aged 20–79 years (n=956) at the final registration of the VOPP (V). Effects of the VOPP interventions directed at environmental risk factors for falls and the promotion of physical activity were examined in people aged ≥ 65 years (IV). The incidence of forearm and hip fractures was studied amongst middle-aged and elderly individuals in the intervention and the control communities during the study period 1987–2001 (VI). The exercise group (n=15) in the weight-bearing training study showed increases in BMD at the greater trochanter (p&lt;0.01), one-leg stance balance with the eyes closed and coordination tests (p&lt;0.05), and aerobic capacity (p&lt;0.05). No significant difference was found when the groups were compared concerning changes in the different tests during the intervention period (I). In the balance-training study, the exercise group showed post-training improvement in the following tests: standing on the right leg with eyes closed (p&lt;0.01), standing on the right leg (p&lt;0.01) and on the left leg (p&lt;0.05) while turning the head, and walking 30 metres (p&lt;0.01). There were significant differences between the groups in these tests when changes were compared at the post-intervention test (II). Age (p&lt;0.0001) and body mass index (p≤.0001) were associated with forearm BMD in both sexes. Reported moderate physical activity levels in men were positively associated with forearm BMD (p&lt;0.05) (III). In both sexes, reported moderate (p&lt;0.05) and high (women p&lt;0.05 and men p&lt;0.001) physical activity levels were positively associated with calcaneal stiffness. The correlation coefficient between forearm BMD and calcaneal stiffness was 0.58 in women and 0.34 in men (V). Persons aged ≥ 65 years at the follow-up in 1994 reported more use of shoe/cane spikes and moderate physical activity levels compared to controls (IV). There was no change in the general incidence of forearm and hip fractures between the communities for the study period. However, there was a tendency towards decreasing incidence of forearm and trochanteric hip fracture in both sexes during the late intervention period in the intervention community (VI). A community-based intervention programme aimed at reducing the incidence of osteoporotic fractures must be regarded as a long-term project and should preferably be monitored over an extended post-intervention period. / On the day of the public defence the statuses of articles IV and V were Submitted and VI was Manuscript