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Prevalence of Achilles tendinopathy increases with age, leading to a weaker tendon with predisposition to rupture. Previous studies, investigating Achilles tendon (AT) properties, are restricted to standardized isometric conditions. Knowledge regarding the influence of age and pa-thology on AT response under functional tasks remains limited. Therefore, the aim of the thesis was to investigate the influence of age and pathology on AT properties during a single-leg vertical jump.
Healthy children, asymptomatic adults and patients with Achilles tendinopathy participated. Ultrasonography was used to assess AT-length, AT-cross-sectional area and AT-elongation. The reliability of the methodology used was evaluated both Intra- and inter-rater at rest and at maximal isometric plantar-flexion contraction and was further implemented to investigate tendon properties during functional task. During the functional task a single-leg vertical jump on a force plate was performed while simultaneously AT elongation and vertical ground reaction forces were recorded. AT compliance [mm/N] (elongation/force) and AT strain [%] (elongation/length) were calculated. Differences between groups were evaluated with respect to age (children vs. adults) and pathology (asymptomatic adults vs. patients).
Good to excellent reliability with low levels of variability was achieved in the assessment of AT properties. During the jumps AT elongation was found to be statistical significant higher in children. However, no statistical significant difference was found for force among the groups. AT compliance and strain were found to be statistical significant higher only in children. No significant differences were found between asymptomatic adults and patients with tendinopathy.
The methodology used to assess AT properties is reliable, allowing its implementation into further investigations. Higher AT-compliance in children might be considered as a protective factor against load-related injuries. During functional task, when higher forces are acting on the AT, tendinopathy does not result in a weaker tendon.
During the last decade, high intensity interval training (HIIT) has been used as an alternative to endurance (END) exercise, since it requires less time to produce similar physiological adaptations. Previous literature has focused on HIIT changes in aerobic metabolism and cardiorespiratory fitness, however, there are currently no studies focusing on its neuromuscular adaptations.
Therefore, this thesis aimed to compare the neuromuscular adaptations of both HIIT and END after a two-week training intervention, by using a novel technology called high-density surface electromyography (HDEMG) motor unit decomposition. This project consisted in two experiments, where healthy young men were recruited (aged between 18 to 35 years). In experiment one, the reliability of HDEMG motor unit variables (mean discharge rate, peak-to-peak amplitude, conduction velocity and discharge rate variability) was tested (Study 1), a new method to track the same motor units longitudinally was proposed (Study 2), and the level of low (<5Hz) and high (>5Hz) frequency motor unit coherence between vastus medialis (VM) and lateralis (VL) knee extensor muscles was measured (Study 4). In experiment two, a two-week HIIT and END intervention was conducted where cardiorespiratory fitness parameters (e.g. peak oxygen uptake) and motor unit variables from the VM and VL muscles were assessed pre and post intervention (Study 3).
The results showed that HDEMG is reliable to monitor changes in motor unit activity and also allows the tracking of the same motor units across different testing sessions. As expected, both HIIT and END improved cardiorespiratory fitness parameters similarly. However, the neuromuscular adaptations of both types of training differed after the intervention, with HIIT showing a significant increase in knee extensor muscle strength that was accompanied by increased VM and VL motor unit discharge rates and HDEMG amplitude at the highest force levels [(50 and 70% of the maximum voluntary contraction force (MVC)], while END training induced a marked increase in time to task failure at lower force levels (30% MVC), without any influence on HDEMG amplitude and discharge rates. Additionally, the results showed that VM and VL muscles share most of their synaptic input since they present a large amount of low and high frequency motor unit coherence, which can explain the findings of the training intervention where both muscles showed similar changes in HDEMG amplitude and discharge rates.
Taken together, the findings of the current thesis show that despite similar improvements in cardiopulmonary fitness, HIIT and END induced opposite adjustments in motor unit behavior. These results suggest that HIIT and END show specific neuromuscular adaptations, possibly related to their differences in exercise load intensity and training volume.
Background: Low back pain (LBP) is one of the world wide leading causes of limited activity and disability. Impaired motor control has been found to be one of the possible factors related to the development or persistence of LBP. In particularly, motor control strategies seemed to be altered in situations requiring reactive responses of the trunk counteracting sudden external forces. However, muscular responses were mostly assessed in (quasi) static testing situations under simplified laboratory conditions. Comprehensive investigations in motor control strategies during dynamic everyday situations are lacking. The present research project aimed to investigate muscular compensation strategies following unexpected gait perturbations in people with and without LBP. A novel treadmill stumbling protocol was tested for its validity and reliability to provoke muscular reflex responses at the trunk and the lower extremities (study 1). Thereafter, motor control strategies in response to sudden perturbations were compared between people with LBP and asymptomatic controls (CTRL) (study 2). In accordance with more recent concepts of motor adaptation to pain, it was hypothesized that pain may have profound consequences on motor control strategies in LBP. Therefore, it was investigated whether differences in compensation strategies were either consisting of changes local to the painful area at the trunk, or also being present in remote areas such as at the lower extremities.
Methods: All investigations were performed on a custom build split-belt treadmill simulating trip-like events by unexpected rapid deceleration impulses (amplitude: 2 m/s; duration: 100 ms; 200 ms after heel contact) at 1m/s baseline velocity. A total number of 5 (study 1) and 15 (study 2) right sided perturbations were applied during walking trials. Muscular activities were assessed by surface electromyography (EMG), recorded at 12 trunk muscles and 10 (study 1) respectively 5 (study 2) leg muscles. EMG latencies of muscle onset [ms] were retrieved by a semi-automatic detection method. EMG amplitudes (root mean square (RMS)) were assessed within 200 ms post perturbation, normalized to full strides prior to any perturbation [RMS%]. Latency and amplitude investigations were performed for each muscle individually, as well as for pooled data of muscles grouped by location. Characteristic pain intensity scores (CPIS; 0-100 points, von Korff) based on mean intensity ratings reported for current, worst and average pain over the last three months were used to allocate participants into LBP (≥30 points) or CTRL (≤10 points). Test-retest reproducibility between measurements was determined by a compilation of measures of reliability. Differences in muscular activities between LBP and CTRL were analysed descriptively for individual muscles; differences based on grouped muscles were statistically tested by using a multivariate analysis of variance (MANOVA, α =0.05).
Results: Thirteen individuals were included into the analysis of study 1. EMG latencies revealed reflex muscle activities following the perturbation (mean: 89 ms). Respective EMG amplitudes were on average 5-fold of those assessed in unperturbed strides, though being characterized by a high inter-subject variability. Test-retest reliability of muscle latencies showed a high reproducibility, both for muscles at the trunk and legs. In contrast, reproducibility of amplitudes was only weak to moderate for individual muscles, but increased when being assessed as a location specific outcome summary of grouped muscles. Seventy-six individuals were eligible for data analysis in study 2. Group allocation according to CPIS resulted in n=25 for LBP and n=29 for CTRL. Descriptive analysis of activity onsets revealed longer delays for all muscles within LBP compared to CTRL (trunk muscles: mean 10 ms; leg muscles: mean 3 ms). Onset latencies of grouped muscles revealed statistically significant differences between LBP and CTRL for right (p=0.009) and left (p=0.007) abdominal muscle groups. EMG amplitude analysis showed a high variability in activation levels between individuals, independent of group assignment or location. Statistical testing of grouped muscles indicated no significant difference in amplitudes between LBP and CTRL.
Discussion: The present research project could show that perturbed treadmill walking is suitable to provoke comprehensive reflex responses at the trunk and lower extremities, both in terms of sudden onsets and amplitudes of reflex activity. Moreover, it could demonstrate that sudden loadings under dynamic conditions provoke an altered reflex timing of muscles surrounding the trunk in people with LBP compared to CTRL. In line with previous investigations, compensation strategies seemed to be deployed in a task specific manner, with differences between LBP and CTRL being evident predominately at ventral sides. No muscular alterations exceeding the trunk could be found when being assessed under the automated task of locomotion. While rehabilitation programs tailored towards LBP are still under debate, it is tempting to urge the implementation of dynamic sudden loading incidents of the trunk to enhance motor control and thereby to improve spinal protection. Moreover, in respect to the consistently observed task specificity of muscular compensation strategies, such a rehabilitation program should be rich in variety.
BACKGROUND: The etiology of low back pain (LBP), one of the most prevalent and costly diseases of our time, is accepted to be multi-causal, placing functional factors in the focus of research. Thereby, pain models suggest a centrally controlled strategy of trunk stiffening in LBP. However, supporting biomechanical evidence is mostly limited to static measurements during maximum voluntary contractions (MVC), probably influenced by psychological factors in LBP. Alternatively, repeated findings indicate that the neuromuscular efficiency (NME), characterized by the strength-to-activation relationship (SAR), of lower back muscles is impaired in LBP. Therefore, a dynamic SAR protocol, consisting of normalized trunk muscle activation recordings during submaximal loads (SMVC) seems to be relevant. This thesis aimed to investigate the influence of LBP on the NME and activation pattern of trunk muscles during dynamic trunk extensions.
METHODS: The SAR protocol consisted of an initial MVC reference trial (MVC1), followed by SMVCs at 20, 40, 60 and 80% of MVC1 load. An isokinetic trunk dynamometer (Con-Trex TP, ROM: 45° flexion to 10° extension, velocity: 45°/s) and a trunk surface EMG setup (myon, up to 12 leads) was used. Extension torque output [Nm] and muscular activation [V] were assessed in all trials. Finally, another MVC trial was performed (MVC2) for reliability analysis. For SAR evaluation the SMVC trial values were normalized [%MVC1] and compared inter- and intra-individually.
The methodical validity of the approach was tested in an isometric SAR single-case pilot study (S1a: N = 2, female LBP patient vs. healthy male). In addition, the validity of the MVC reference method was verified by comparing different contraction modes (S1b: N = 17, healthy individuals). Next, the isokinetic protocol was validated in terms of content for its applicability to display known physiological differences between sexes in a cross-sectional study (S2: each n = 25 healthy males/females). Finally, the influence of acute pain on NME was investigated longitudinally by comparing N = 8 acute LBP patients with the retest after remission of pain (S3). The SAR analysis focused on normalized agonistic extensor activation and abdominal and synergistic extensor co-activation (t-tests, ANOVA, α = .05) as well as on reliability of MVC1/2 outcomes.
RESULTS: During the methodological validation of the protocol (S1a), the isometric SAR was found to be descriptively different between individuals. Whereas torque output was highest during eccentric MVC, no relevant difference in peak EMG activation was found between contraction modes (S1b). The isokinetic SAR sex comparison (S2), though showing no significant overall effects, revealed higher normalized extensor activation at moderate submaximal loads in females (13 ± 4%), primarily caused by pronounced thoracic activation. Similarly, co-activation analysis resulted in significantly higher antagonistic activation at moderate loads compared to males (33 ± 9%). During intra-individual analysis of SAR in LBP patients (S3), a significant effect of pain status on the SAR has been identified, manifesting as increased normalized EMG activation of extensors during acute LBP (11 ± 8%) particularly at high load. Abdominal co-activation tended to be elevated (27 ± 11%) just as the thoracic extensor parts seemed to take over proportions of lumbar activation. All together, the M. erector spinae behaviour during the SAR protocol was rather linear with the tendency to rise exponentially during high loads. For the level of normalized EMG activation during SMVCs, a clear increasing trend from healthy males to females over to non-acute and acute LBP patients was discovered. This was associated by elevated antagonistic activation and a shift of synergistic towards lumbar extensor activation. The MVC data revealed overall good reliability, with clearly higher variability during acute LBP.
DISCUSSION: The present thesis demonstrates that the NME of lower back muscles is impaired in LBP patients, especially during an acute pain episode. A new dynamic protocol has been developed that makes it possible to display the underlying SAR using normalized trunk muscle EMG during submaximal isokinetic loads. The protocol shows promise as a biomechanical tool for diagnostic analysis of NME in LBP patients and monitoring of rehabilitation progress. Furthermore, reliability not of maximum strength but rather of peak EMG of MVC measurements seems to be decreased in LBP patients. Meanwhile, the findings of this thesis largely substantiate the assumptions made by the recently presented ‘motor adaptation to pain’ model, suggesting a pain-related intra- and intermuscular activation redistribution affecting movement and stiffness of the trunk. Further research is needed to distinguish the grade of NME impairment between LBP subgroups.
Since 1998, elite athletes’ sport injuries have been monitored in single sport event, which leads to the development of first comprehensive injury surveillance system in multi-sport Olympic Games in 2008. However, injury and illness occurred in training phases have not been systematically studied due to its multi-facets, potentially interactive risk related factors. The present thesis aim to address issues of feasibility of establishing a validated measure for injury/illness, training environment and psychosocial risk factors by creating the evaluation tool namely risk of injury questionnaire (Risk-IQ) for elite athletes, which based on IOC consensus statement 2009 recommended content of preparticipation evaluation(PPE) and periodic health exam (PHE).
A total of 335 top level athletes and a total of 88 medical care providers from Germany and Taiwan participated in tow “cross-sectional plus longitudinal” Risk-IQ and MCPQ surveys respectively. Four categories of injury/illness related risk factors questions were asked in Risk-IQ for athletes while injury risk and psychological related questions were asked in MCPQ for MCP cohorts. Answers were quantified scales wise/subscales wise before analyzed with other factors/scales. In addition, adapted variables such as sport format were introduced for difference task of analysis.
Validated with 2-wyas translation and test-retest reliabilities, the Risk-IQ was proved to be in good standard which were further confirmed by analyzed results from official surveys in both Germany and Taiwan. The result of Risk-IQ revealed that elite athletes’ accumulated total injuries, in general, were multi-factor dependent; influencing factors including but not limited to background experiences, medical history, PHE and PPE medical resources as well as stress from life events. Injuries of different body parts were sport format and location specific. Additionally, medical support of PPE and PHE indicated significant difference between German and Taiwan.
The result of the present thesis confirmed that it is feasible to construct a comprehensive evalua-tion instrument for heterogeneous elite athletes cohorts’ risk factor analysis for injury/illness oc-curred during their non-competition periods. In average and with many moderators involved, Ger-man elite athletes have superior medical care support yet suffered more severe injuries than Tai-wanese counterparts. Opinions of injury related psychological issues reflected differently on vari-ous MCP groups irrespective of different nationalities. In general, influencing factors and interac-tions existed among relevant factors in both studies which implied further investigation with multiple regression analysis is needed for better understanding.
The human immunodeficiency virus (HIV) has resisted nearly three decades of efforts targeting a cure. Sustained suppression of the virus has remained a challenge, mainly due
to the remarkable evolutionary adaptation that the virus exhibits by the accumulation of drug-resistant mutations in its genome. Current therapeutic strategies aim at achieving and maintaining a low viral burden and typically involve multiple drugs. The choice of optimal combinations of these drugs is crucial, particularly in the background of treatment failure having occurred previously with certain other drugs. An understanding of the dynamics of viral mutant genotypes aids in the assessment of treatment failure with a certain drug
combination, and exploring potential salvage treatment regimens.
Mathematical models of viral dynamics have proved invaluable in understanding the viral life cycle and the impact of antiretroviral drugs. However, such models typically use simplified and coarse-grained mutation schemes, that curbs the extent of their application to drug-specific clinical mutation data, in order to assess potential next-line therapies. Statistical
models of mutation accumulation have served well in dissecting mechanisms of resistance evolution by reconstructing mutation pathways under different drug-environments. While these models perform well in predicting treatment outcomes by statistical learning, they do not incorporate drug effect mechanistically. Additionally, due to an inherent lack of
temporal features in such models, they are less informative on aspects such as predicting mutational abundance at treatment failure. This limits their application in analyzing the
pharmacology of antiretroviral drugs, in particular, time-dependent characteristics of HIV therapy such as pharmacokinetics and pharmacodynamics, and also in understanding the impact of drug efficacy on mutation dynamics.
In this thesis, we develop an integrated model of in vivo viral dynamics incorporating drug-specific mutation schemes learned from clinical data. Our combined modelling
approach enables us to study the dynamics of different mutant genotypes and assess mutational abundance at virological failure. As an application of our model, we estimate in vivo
fitness characteristics of viral mutants under different drug environments. Our approach also extends naturally to multiple-drug therapies. Further, we demonstrate the versatility of our model by showing how it can be modified to incorporate recently elucidated mechanisms of drug action including molecules that target host factors.
Additionally, we address another important aspect in the clinical management of HIV disease, namely drug pharmacokinetics. It is clear that time-dependent changes in in vivo
drug concentration could have an impact on the antiviral effect, and also influence decisions on dosing intervals. We present a framework that provides an integrated understanding
of key characteristics of multiple-dosing regimens including drug accumulation ratios and half-lifes, and then explore the impact of drug pharmacokinetics on viral suppression.
Finally, parameter identifiability in such nonlinear models of viral dynamics is always a concern, and we investigate techniques that alleviate this issue in our setting.