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Multiple Sclerosis (MS) is a chronic progressive disease which presents with a variety of cognitive, motor and sensory deficits. Rehabilitation strategies to help manage some of these deficits include increasing physical activity and undertaking therapeutic exercise. A literature review begins this thesis and where relevant gaps are highlighted. These include; minimal literature on the long-term effects of therapeutic exercise, the views of those with MS taking part in therapeutic exercise and the characteristics of outcome measures used to assess those with MS. To address these areas three studies are presented related to therapeutic exercise for those moderately affected with MS (defined as an Expanded Disability Status Score of 5 to 6.5). In the first study, a 12-week therapeutic exercise programme was delivered to twenty people with MS, whilst 12 people acted as controls who received usual care. Clinical outcomes were assessed at five time points over the intervention and 12-month follow-up period of the study. No statistically significant results emerged to suggest the intervention was effective, however calculated effect sizes indicated the intervention had a positive effect on areas related to the physiological (strength, mobility, fatigue and body composition), functional (mobility, balance and activity participation) and psychological (mood and quality of life) status of participants. The second study sought to establish the views and opinions of participants, who had attended the exercise intervention. Three inter-related themes emerged. These were (1) the Exercise Class, which developed as a bridge to allow participants to realise (2) the Benefits of the Class, helping them to overcome (3) Barriers to Exercise. Results suggested the benefits to participating in exercise and the exercise intervention included social support and symptom improvement. Barriers to exercise included perceived psychosocial factors, symptoms and lack of service. A third study investigated the test re-test reliability of four outcome measures used in the first study, calculations were done to establish the clinically significant change and precision of the outcome measures. The test re-test reliability of the outcome measures was good, with the calculated clinical change and precision of the outcome measures in those moderately affected with MS highlighting the problems of assessing those with MS. The overall investigation suggests that therapeutic exercise and monitoring its effect in MS is good. Clinical and research recommendations emerged from this work, these include that the heterogeneity of symptoms presented in MS should be considered in future research designs and that group therapeutic exercise may improve physiological, functional and psychological status of those with MS, with the social benefits important to participants.

An epidemiological study into the incidence of ankle sprain in elite and non-elite athletes was carried out to collect data on the incidence of sports injuries focusing specifically on ankle sprains in elite and non-elite athletes. Furthermore, to develop and validate a questionnaire to be used to collect data on the residual symptoms associated with a history of ankle sprain and functional instability. Ankle sprains accounted for 16% of all injuries and symptoms of functional instability were reported by 95% of athletes that reported sustaining an ankle sprain during the study. The questionnaire was then used to recruit subjects (19 subjects with a history of unilateral ankle sprain and functional instability and 19 healthy controls) for the subsequent experiments. Anteroposterior and medio-lateral postural sway in single-limb stance was examined using a KistierTM force platform. Each subject underwent twelve postural sway tests: three on each leg with eyes open and eyes closed. With eyes closed the injured ankle had significantly greater medial (p=O.001) and lateral (p=O.007) postural sway than the uninjured ankle. With eyes open the injured and uninjured ankles had similar postural control. With eyes open the injured ankle had significantly greater anterior (p=O.021, p=O.Oll) and posterior (p=O.019, p=O.018) postural sway than the dominant and non-dominant ankles respectively. With eyes closed the injured ankles had significantly greater medial (p=O.008, p=O.008) and lateral (p=O.014, p=O.015) postural sway than the dominant and non-dominant ankles respectively. The reaction time of peroneus longus, peroneus brevis, tibialis anterior and extensor digitorum longus to a non-pathological lateral ankle sprain mechanism was examined using a purpose built tilt platform. The platform had two moveable plates so that either ankle could be tilted spontaneously into combined plantarflexion and inversion. Electromyography was performed on each muscle and subjects had each ankle tilted six times. A computer-based onset detection method was developed to provide an objective method for identifying the onset of electromyography and tilt platform activity and calculating muscular reaction times. The injured ankle peroneus longus, peroneus brevis and tibialis anterior reaction times were significantly slower.

Study 1 quantified the validity and repeatability of an automated on-line (ON) gas analysis system during sub-maximal loaded marching (LM) against that of the Douglas Bag (DB) approach. The 95% ratio Limits of Agreement (LoA) revealed the ON system systematically overestimated V02 by -16% (1.16 (x/-i-1.19). The Bland and Altman plots revealed DB repeatability was almost two-fold better than ON (-9% vs. -15%), thus the DB approach should be used subsequently to measure human expired gases. Study 2 investigated the difference between an LM maximal oxygen uptake protocol (LMp) versus a standard running protocol (Rp). The LMp V02max was lower than Rp (48.6 ± 4.3 ml·kg-I·min-I vs. 51.3 ± 4.0 ml·kg-I·min-I, P=0.001). Thus, the quantification of sub-maximal LM exercise intensity will be underestimated by -5% if derived from a running tiOzmax protocol. Study 3 investigated the repeatability of accepted and potential determinants of Loaded Marching Performance (LMP). The LoA revealed the repeatability of Loaded Marching Economy (LME) (0.98 (x/-i-1.09», V02max (1.01 (xl-i-1.07», upper body dynamic strength (1.01 (x/-i- 1.11», and anthropometric measures (1.00 (x/-i- 1.02» to (1.00 (x/-i- 1.07» was reasonable, but dynamic leg strength (1.06 (x/-i-1.14» and isometric strength (1.00 (x/-i-1.12» to (0.99 (x/-i-1.l6» were large. Study 4 established the determinants of 2.4 km LMP from a test battery performed at the beginning of British Army infantry training. The best mathematical model of LMP included the independent variables of LME (r=0.65), 2.4 km run time (r=0.42), and peak static lift strength (r=0.48). This explained 65% of the variation in LMP, and had a prediction error of ± 51 s. Mathematically, LME and 2.4 km run time exerted the greatest influence on LMP, whereas the influence of static lift strength on LMP was small. Study 5 investigated the physical and physiological responses of the established determinants of LMP during 24 weeks of British Army infantry training. Loaded marching performance improved 7.0% (900 s to 837 s, P=0.001), LME 9.6% (2.28 I·min- I to 2.06 I·min- I , P ...

The development of powerful muscle function is fundamental to the strength and conditioning process. Optimal load resistance training uses the load that maximises power output to more efficiently achieve this. However, research has shown that factors including measurement method and training status can significantly influence the optimal load. The five experimental studies of this thesis investigated these factors. First, the way in which the positive lifting phase is identified was examined to establish the underpinnings of ballistic resistance exercise preference over traditional alternatives. The results of this study showed that the positive lifting phase of ballistic resistance exercise did not consider the deceleration phase and when this was applied to traditional resistance exercise a greater portion of the positive lifting phase was spent accelerating the barbell. This finding suggested that the assumption of ballistic resistance exercise superiority is theoretically unfounded whilst potentially posing a greater risk of injury. The next three studies established the reliability and suitability of different methods used to measure resistance exercise power output. The second study revealed that the most practically applicable, theoretically sound and reliable method of obtaining power output used the barbell kinematics approach where the acceleration of the barbell was considered but body mass excluded. This may have important implications for field-based methods that are underpinned by this approach. The results of the third and fourth study reinforced the findings of study two. The third study considered whether neglecting horizontal barbell power caused the barbell kinematics approach to underestimate resistance exercise power output, and established that the horizontal contribution did not exceed 2%. The effect of bilateral asymmetries on barbell power output was examined in the fourth study and demonstrated that although ground kinetic side differences reached 21% they were not transmitted to left and right barbell end power outputs, with left and right bar end differences remaining below 4%. The barbell kinematics approach was then used in the fifth study, to show that stronger, more experienced individuals generated greater mean (17 to 35%) and peak (20 to 45%) power outputs and maximised mean and peak power with loads that were considerably less (3 to 15% of IRM less) than their weaker, less experienced counterparts. Training status did not significantly affect power and optimal load reliability. To summarise, measurement methods should not be used interchangeably. The barbell kinematics approach is recommended to obtain resistance exercise power output but the optimal load should be prescribed on an individual athlete basis and routinely monitored for maximum accuracy.

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Administration of recombinant human erythropoietin (rHuEpo) improves endurance performance. Hence rHuEpo is, allegedly, frequently subject to abuse by athletes, although rHuEpo is prohibited by the World Anti-Doping Agency. A transcriptomic-based longitudinal screening approach has the potential to improve further the performance of current detection methods. AIM: To assess the effects of rHuEpo on blood gene expression profiles in order to identify a “molecular signature” of rHuEpo doping. METHODS: 19 Caucasian trained males at sea-level (Scotland – SCO) and 20 Kenyan endurance runners at moderate altitude (~2,150 m, Kenya – KEN) received rHuEpo injections of 50 IU∙kg-1 body mass every two days for 4 weeks. Blood was obtained 2 weeks before, during and 4 weeks after administration. 3,000 m time trial performance was measured pre, post administration and at the end of the study. RNA was extracted from blood stabilized in Tempus RNA tubes, amplified, labelled and hybridized to Illumina HumanHT-12v4 Expression BeadChips. Expression data was analyzed using Rank Products with a 5% false discovery rate and an additional 1.5 fold-change threshold. A subset of target and housekeeping genes was further validated using QuantiGene Plex assay. RESULTS: Despite markedly different baseline values between SCO and KEN, as exemplified by the haematocrit (41.9 ± 1.8% vs. 45.3 ± 2.6, p < 0.001), key blood parameters significantly increased during rHuEpo in both groups (p < 0.001) to reach similar levels at the end of administration (49.2 ± 2.0% vs. 49.6 ± 2.6, p = 0.638). The relative improvements in running performance post rHuEpo (~5%) and 4 weeks post administration (~3%) compared to baseline were of similar magnitude in both groups (p > 0.188). These results confirmed that the perturbation involving rHuEpo worked effectively. Relative to baseline, the expression of hundreds of genes were found to be altered by rHuEpo. In particular, 30 transcripts were already differentially expressed two days after the first injection while 15 transcripts were profoundly up-regulated during and subsequently down-regulated up to 4 weeks post administration in both groups. Importantly, the same pattern was observed in all subjects. The functions of the discovered genes were mainly related to either the functional or structural properties of the erythrocyte or to the cell cycle and its regulation. CONCLUSION: This research successfully identified the blood “molecular signature” of rHuEpo administration and provides the strongest evidence to date that gene biomarkers have the potential to substantially improve the performance of current anti-doping methods such as the Athlete Biological Passport for rHuEpo detection.

Increased relative risk of non-contact anterior cruciate ligament (ACL) injury has been attributed to numerous biomechanical, anatomical and neuromuscular factors. Females are at greater relative risk of non-contact ACL injury compared with males. Dynamic knee stability is an important component required to reduce relative risk of injury, especially to the knee joint. It is difficult to directly measure knee stability; however the eccentric ability of the hamstrings to co-contract to counter the torque produced by concentric quadriceps actions during knee extension is important in stabilising the knee (determined as the functional H/Q ratio [FH/Q]). One of the proposed reasons for a greater incidence of non-contact ACL injury in females is a reduced capacity for neuromuscular functioning to stabilise the knee joint effectively. Most injuries occur in the second half of an athletic event when fatigue is commonly present, therefore identifying fatigue as a potential risk factor for ACL injury and this may allow for the development of improved prevention strategies. The three experimental studies included within this thesis (chapter 4-6) have generated novel data on sex differences in the FH/Q ratio and neuromuscular performance prior to and following a downhill running fatigue task. One hundred and ten healthy males (n=55; mean ± SD 29 ± 5 yrs) and females (n=55; mean ± SD 27 ± 6 yrs) were recruited from the university population. Isokinetic torque of the hamstrings and quadriceps was determined at 60, 120 and 240˚·s–1with the hip flexed at 0°. Range of movement of the knee joint was 90° with 0° determined as full volitional extension. Concentric (CON) torque was determined first followed by eccentric (ECC) torque, with the slowest velocity tested first. Torque was gravity corrected and filtered to only include constant velocity periods. For functional relevance FH/Q ratio was determined at 15, 30, 45º (as these are the joint angles where injury is most likely to occur) and where peak torque (PT) was achieved (to compare with the extant literature) for each movement velocity. Surface electromyography was recorded from the semitendinosus (ST), semimembranosus (SM) and biceps femoris (BF) of the dominant limb using an 8-channel DelSys EMG telemetry system. The biodex square wave synchronization pulse was configured with the EMG software via a trigger system so that EMG and torque data were completely time aligned. Raw EMG data were collected at a sampling frequency of 1024 Hz and included a common mode rejection ratio of <80 dB and an amplifier gain of 1000. Raw EMG data was band pass filtered at 20 – 450 Hz. The electromechanical delay (EMD) was determined as the time delay between the onset of muscle activation (change in activation of +15 μV) and onset of torque production (9.6 N·m) according to the procedures described by Zhou et al (1995). The aim of the first study (chapter 4) was to explore sex differences in the FH/Q ratio whilst taking into account joint angle and movement velocity. A 2 (sex) x 3 (movement velocity) x 4 (joint angle) ANOVA was performed to determine interactions and main effects. FH/Q ratio ranged from 59 to 98% in females and 66 to 109% in males across joint angles and movement velocities. No significant differences between males and females in age but males were significantly taller and had greater body mass. Irrespective of sex the FH/Q ratio increased with joint angle and movement velocity to improve knee stability during high velocity movement and near full extension. However, the FH/Q ratio is significantly lower in females compared with males and importantly this sex difference increases as movement velocity increases. Females have a lower FH/Q ratio than males close to full knee extension and during high velocity movements, both of which are predisposing factors for increased injury risk. This reduced FH/Q ratio may impair dynamic knee stability in females during fast velocity movements and may predispose them to a greater relative risk of knee injury. The aim of the second study (chapter 5) was to examine sex differences in the EMD of the hamstring muscles during eccentric muscle actions at 60, 120 and 240˚·s–1. A 2 (sex) x 3 (muscle group) x 3 (movement velocity) ANOVA was performed to determine interactions and main effects. During eccentric hamstring muscle actions there were no differences in the EMD of the 3 muscles examined. Irrespective of sex, significant main effects for angular velocity was demonstrated, indicating an increase in the delay time with increasing angular velocity. This increased delay during fast velocity movements may account for the increased risk of injury during fast movements. No significant sex differences in EMD was found irrespective of movement velocity of muscle examined, suggesting that females do not have impaired neuromuscular performance of the hamstring compared with males during eccentric hamstring muscle actions in the rested state. The aim of the third study (chapter 6) was to examine the effects of a fatigue task on sex differences of the FH/Q ratio and EMD. The procedures used in study 1 and 2 were repeated pre and post a downhill running fatigue task to explore fatigue related effects on neuromuscular functioning. Each participant performed a 40 min intermittent downhill running protocol consisting of 5 × 8 min bouts on a -10% decline, with 2 min standing rest between each bout. Irrespective of sex, joint angle or angular velocity, the FH/Q ratio was lower and EMD of hamstrings muscle was longer post-fatigue compared to pre-fatigue. Significant interactions between sex and time (pre-post) for the FH/Q ratio and EMD of hamstring muscles were found. The interactions showed a significantly lower FH/Q ratio and significantly longer EMD post fatigue in females compared to males. These data suggest that functional stability of the knee is reduced when fatigue is present and the impact of fatigue is greater in females. The findings of this thesis indicate the importance of determining the FH/Q ratio using angle specific torque as well as taking into account movement velocity, rather than simply using PT values to monitor muscle function of the knee. The findings of the present thesis support the notion that fatigue compromises the stability of the knee by reducing the FH/Q ratio and lengthening EMD. These effects are greater in females compared to males and may predispose them to greater relative risk of injury. Therefore, movement velocity, joint angle and fatigue resistance all need to be considered when designing training programmes to reduce the relative risk of injury. The focus of such training should be aimed at eccentric conditioning of the hamstring muscles to improve both muscular and neuromuscular functioning to limit the fatigue related effects, especially in females.

There are currently no calibration models that allow whole body density in professional footballers to be estimated. As such, there is a need to develop practical calibration models in order to make sound body composition judgements. The aim of this thesis is threefold. Firstly, to examine the measurement reliability of a range of anthropometric measures, residual lung volume, air displacement plethysmography and hydrostatic weighing. Secondly, to establish reliability and precision of body composition measures used within existing calibration models which estimate whole body density from the criterion of hydrostatic weighing. Thirdly, to develop and cross-validate new calibration models for professional footballers.

The complexity of the pathophysiology of tennis elbow is reflected by the lack of consensus on management and remains a therapeutic challenge. This study was a prospective randomised, assessor-blinded trial. 64 patients with tennis elbow referred by their GP to either the physiotherapy, orthopaedic or MSK CAT services, subject to eligibility criteria, were randomised into one of 3 treatment arms: injection, ultrasound or exercise, to which the assessor remained blinded. The outcome measures of thermal difference, median frequency (MDF), patient-rated tennis elbow evaluation questionnaire (PRTEE), pain-free grip strength (PFG) and patient preference were assessed twice at baseline, at 10 days, 6 weeks and 6 months and analysed as an intention to treat analysis. In the short term of 6 weeks injection was the most effective treatment demonstrating both statistically significant and minimum clinically important differences (MCID) for PFG and PRTEE in comparison to ultrasound and exercise. Patients had a strong preference for injection and a strong aversion for exercise. No statistically significant differences were found between ultrasound and exercise although a MCID was found in favour of ultrasound for thermal difference and MDF at 10 days. In to the long term of 6 months, although this was on a limited subgroup, no statistically significant differences were found between any of the groups. A MCID was found in favour of ultrasound for MDF and a MCID was found in favour of exercise over injection for all aspects of PRTEE and over ultrasound for PRTEE pain only. This research supports the superior effectiveness of injection in the short term of 6 weeks and should be advocated for patients who present early with severe limiting pain and have important short term goals, although patients need to be warned that a 1/3rd will have a recurrence of symptoms within 6 months. In contrast, for those patients who present with moderate to low pain physiotherapy including exercise and/ or ultrasound should be advocated. Thermal difference is a sensitive outcome measure for tennis elbow. Continuous 3 MHz therapeutic ultrasound at 2W/cm2 for 5 minutes utilises thermal effects which optimise the healing process and demonstrate an accumulative effect of ultrasound in to the long term. Further research on the effectiveness of a combination of injection with physiotherapy is required.