The trainability of youth at specific periods during growth and maturation has become a key issue in paediatric exercise science. The development of physical capacities such as movement speed, strength and power is difficult to predict in youth meaning that the structuring of training can be a significant challenge for coaches. Accordingly, methodologically sound research is required to underpin a more informed approach to the formulation of programmes of physical development. To this end, the purpose of this work was to investigate the trainability of youth athletes at specific stages during maturation (pre-, mid-, and post-peak height velocity) by addressing some of the shortcomings of the existing body of literature. Short-term controlled interventions were undertaken and they extended from the findings of three meta-analytical reviews, all of which examined the effect of training on the development of speed, strength and power in youths aged 9 to 18. These investigations were focused on the manipulation of modifiable factors, such as the training stimulus, as opposed to non-modifiable factors, such as maturity (which was generally controlled for). With some exceptions, which are potentially explainable, speed, strength and power were, on the whole, more trainable in youths as they advanced in maturation with the mid-peak height velocity phase being a particularly important time for the development of these capacities. This could indicate the presence of a maturational threshold which moderates responses to training but this can also be coincident with a period of impaired performance potentially related to reduced motor control due to rapid growth rates. Because of the way speed, strength and power can develop in youth athletes, the pre-peak height velocity phase of development may be more conducive to neuromuscular training with a coordinative component which establishes the movement competency required for more advanced techniques. An intensification of resistance (strength) training can be of benefit during mid-peak height velocity though impaired movement or a higher susceptibility to injury could compel coaches to reduce sprint (speed) and/or plyometric (power) training at this time. During the post-peak height velocity phase, athletes can be transitioned to more advanced training techniques, that are traditionally used with adults, if they possess the necessary coordination and experience to do so. Regardless of the results in this work, at every stage of development it is important for coaches to make programming decisions for youth athletes based, primarily, on training age and movement competency with the above maturity-related recommendations being suitable for those who have been exposed to high quality training from an early age.

Albumins Redhill and Warwick-2 are monomeric, slow albumin variants discovered serendipitously in sera obtained from two unrelated families living in the U.K. Albumin Redhill was purified both by chromatofocusing and preparative polyacrylamide gel electrophoresis whereas albumin Warwick-2 was obtained exclusively by the latter technique. Following isolation, selective cleavage at methionine and tryptophan residues using specific chemical reagents was employed to examine the primary structure of each variant compared to the structure of normal albumin. Albumin Redhill is a proalbumin; the intracellular precursor of albumin. An amino acid substitution within the N-terminal propeptide has prevented normal cleavage of the additional residues in vivo. A second mutation lies in the C-terminal region of the sequence, probably between residues 503 and 585. This mutation is unusual in that it appears to involve the insertion of a short sequence, corresponding to approximately ten to twelve amino acids. The N-terminal residue is L-arginine; L-leucine was identified as the C-terminal end group. Albumin Warwick-2 contains an amino acid substitution in the N-terminal region of the sequence, between residues 1 and 87. This variant is not a proalbumin, having L-aspartic acid in the N-terminal position. The C-terminal residue is L-leucine. The isoelectric point of albumin Redhill is more acidic than that of albumin A, at pH 4.74-4.75, whereas albumin Warwick-2 becomes isoelectric on the basic side of albumin A, at pH 5.0-5.02. Both variants share a common antigenicity with albumin A and are present in a lesser quantity than the normal allotype in the serum. Albumin Redhill shows a reduced binding capacity for copper and nickel while albumin Warwick-2 binds these two metals normally. Both albumins show decreased binding for bilirubin and differential binding towards a series of organic dyes, but bind palmitate similarly to albumin A.

Kinaesthetic Learning Activities (KLA) are techniques for enhancing the motor learning process to provide a deep understanding of fundamental skills in particular disciplines. With KLA learning takes place by carrying out a physical activity to transform empirical achievements into representative cognitive understanding. In disciplines such as medical education, frequent hands-on practice of certain motor skills plays a key role in the development of medical students' competency. Therefore it is essential that clinicians master these core skills early on in their educational journey as well as retain them for the entirety of their career. Transferring knowledge of performing dexterous motor skills, such as clinical examinations, from experts to novices demands a systematic approach to quantify relevant motor variables with the help of medical experts in order to form a reference best practice model for target skills. Additional information (augmented feedback) on certain aspects of movements could be extracted from this model and visualised via multi-modal sensory channels in order to enhance motor performance and learning processes. This thesis proposes a novel KLA methodology to significantly improve the quality of palpation training in medical students. In particular, it investigates whether it is possible to enhance the existing abdominal palpation skills acquisition process (motor performance and learning) with provision of instructional concurrent and terminal augmented feedback on applied forces by the learner's hand via an autonomous multimodal displays. This is achieved by considering the following: identifying key motor variables with help of medical experts; forming a gold standard model for target skills by collecting pre-defined motor variables with an innovative quantification technique; designing an assessment criteria by analysing the medical experts' data; and systematically evaluating the impact of instructional augmented feedback on medical students' motor performance with two distinct assessment approaches(a machine-based and a human-based). In addition, an evaluation of performance on a simpler task is carried out using a game-based training method, to compare feedback visualisation techniques, such as concurrent visual and auditory feedback as used in a serious games environment, with abstract visualisation of motor variables. A detailed between-participants study is presented to evaluate the effect of concurrent augmented feedback on participants' skills acquisition in the motor learning process. Significant improvement on medical students' motor performance was observed when augmented feedback on applied forces were visually presented (H(2) = 6:033, p < :05). Moreover, a positive correlation was reported between computer-generated scores and human-generated scores, r = :62, p (one-tailed) < :05. This indicates the potential of the computer-based assessment technique to assist the current assessment process in medical education. The same results were also achieved in a blind-folded (no-feedback) transfer test to evaluate performance and short-term retention of skills in the game-based training approach. The accuracy in the exerted target force for participants in the game-playing group, who were trained using the game approach (Mdn = 0:86), differed significantly from the participants in control group, who trained using the abstract visualisation of the exerted force value (Mdn = 1:56), U = 61, z = -2:137, p < :05, r = -0:36. Finally, the usability of both motor learning approaches were surveyed via feedback questionnaires and positive responses were achieved from users. The research presented shows that concurrent augmented feedback significantly improves the participants' motor control abilities. Furthermore, advanced visualisation techniques such as multi-modal displays increases the participants' motivation to engage in learning and to retain motor skills.

Diabetes is a multisystemic disease that affects the whole human body, in particular, the musculoskeletal system. Muscles, tendons, ligaments and bone marrow are its main victims, the foot being the most common target. Changes in its anatomy can occur rapidly, and therefore an early diagnosis is imperative in order to provide the appropriate medical care, thus avoiding amputation which is a high factor of morbidity. In order to understand the biomechanical implications of the disease, it is necessary to develop new and improved models that allow the study of the foot during gait. The difficulties arising in foot modelling are inherent in its complex composition, thus most models simplify the foot geometry, structure, materials and kinetic analysis. This thesis presents a new approach towards foot modelling, combining readily available non-invasive methodologies to develop multi-segment foot models. This research helps in the in-depth understanding of the effects of changes in structure and shape of the foot brought about by diabetes and in the evaluation of the effects of interventions and long-term rehabilitation. Intermediate results are presented in order to establish the reliability of the proposed methods, developing first a new method for simultaneous plantar pressure and gait study. New approaches to muscle-tendon length and moment arm measurement are tested and validated, following an analysis of different pennation angle assumptions for force production assessment. Both extrinsic and intrinsic muscles are included in the model using the Hill muscle model. Stiffness and damping parameters are estimated on a per-subject basis. In order to model the soft tissue, which is of particular interest in diabetic patients, a model consisting of a system of parallel spring and damper, is proposed. Parameters are presented for 15 subjects with the purpose of characterising the properties of the soft tissue under the calcaneus (heel pad), metatarsal heads and hallux. A further analysis is provided by simulating different diabetic foot injuries and comparing their effect in joint range of movement and moment and soft tissue. Combined, these studies produce a complete subject-specific musculoskeletal and soft tissue model that enhances our understanding of both normal and altered gait.

The mechanisms of neural control of human balance, and in particular upright stance, are still not fully understood. Most authors understand balance to be controlled through relatively simple reflex mechanisms, but some groups propose balance is dominated by higher level control. I develop new semi-automatic techniques which can follow very small changes in muscle length via ultrasonography. I use this technique to uncover a high sensitivity control mechanism in human standing that is more consistent with reflex than higher level control. Further experiments suggest reflex control is present, albeit at a low gain, in a balance control task that is similar to standing, but that higher level control mechanisms dominate. A final investigation into visuo-manual balance suggests that control alternates between actions and sensation which facilitates higher quality sensory feedback. I hypothesise that balance is maintained by parallel neural pathways. Reflex control operates at low gain to increase the time constant of the human inverted pendulum. This facilitates the operation of a higher level controller that is subject to longer time delays. I speculate that higher level serial ballistic control may enable higher quality feedback than would be possible otherwise.

Human motor system plasticity can be quantified using single pulse transcranial magnetic stimulation (TMS) to measure corticospinal excitability. TMS can be used to produce excitability maps and to examine the stimulus-response (SR) relationship. The overall aims of this thesis are (1) to demonstrate that TMS mapping and SR curves can be acquired much faster than has been traditionally possible and (2) that these techniques can be used to study internally externally driven plasticity. By modifying the TMS delivery, it is demonstrated that both the TMS map and the SR curve can be reliably produced in approximately two minutes. These techniques were then used to examine internally driven plasticity via mirror training and visuomotor tracking learning and externally driven plasticity via transcranial alternating current stimulation. Changes in corticospinal excitability were found to be variable both for internally as externally driven plasticity. Nonetheless, these studies highlight that it is possible to rapidly assess changes in corticospinal excitability.

Older adults at a high-risk of falling tend to look away from a current stepping target in order to look at obstacles ahead. This early gaze transfer impairs the accuracy of stepping. It has previously been shown that this maladaptive gaze behaviour is associated with increased anxiety. This thesis aimed to elucidate the causal relationships between anxiety, sub-optimal gaze behaviour and increased falls risk in older adults. In separate experiments we manipulated experimental conditions to: 1) increase older participants anxiety via Social Evaluative Threat 2) reduce anxiety via relaxation exercises and 3) alter the extent to which participants previewed obstacles and walking goals via a gaze training intervention. Increasing older adults’ anxiety resulted in reduced stepping performance, and a measured reduction in anxiety was accompanied by increased stepping performance. There were few effects on eye movement timing characteristics suggesting that these changes in stepping behaviour were not mediated by altered gaze strategies. Route previewing intervention resulted in significant changes to older adults’ gaze behaviour, and improved self-confidence and stepping performance. These findings highlight the possibility of using interventions aimed at reducing anxiety and/or guiding gaze behaviour to address falls-risk in older adults.

Exercise is inherently linked with the production of reactive oxygen and nitrogen species (RONS) resulting in augmented oxidative stress post-exercise. Antioxidant supplements have been proposed to reduce exercise-induced oxidative stress, but this alleviation can potentially negate signalling pathways mediated by RONS. This thesis presents novel findings on the consumption of antioxidant supplements and the effects of habitual supplementation on exercise-induced oxidative stress following a cycling sportive in recreational cyclists (chapters 1 and 2). Consumption of antioxidant supplements is not associated with age, cycling experience or weekly training hours; nor do they provide additional protection in reducing oxidative stress on completion of a cycling sportive. The final two experimental chapters assessed the effect of habitual supplementation on basal levels of endogenous antioxidants and the oxidative stress response to steady-state cycling (chapter 4). And the effect of polyphenol supplementation on cycling recovery, assessed by markers of oxidative stress, inflammation and cycling performance in trained cyclists (chapter 5). Habitual supplementation did not affect baseline concentrations of superoxide dismutase-1 (SOD1), superoxide dismutase-2 (SOD2) or glutathione peroxidase-1 (GPx-1); nor the oxidative stress response to steady-state cycling. Supplementation with a polyphenol drink did not attenuate exercise-induced oxidative stress, inflammation, or improve cycling performance compared to placebo.

It is well accepted that CHO ingestion can improve endurance performance. However, a number of questions remain open regarding fine-tuning CHO intake recommendations during prolonged endurance events. A way to measure the bioavailability of ingested CHO is to measure exogenous CHO oxidation with the use of \(^{13}\)C or \(^{14}\)C tracers. This, however, has been studied only with CHO solutions, predominantly during cycling. In this thesis, we demonstrated that glucose+fructose ingested in the form of gel (1.8 g/min) is as effectively oxidized as an isocarbohydrate solution (1.44±0.29 g/min vs 1.42±0.23 g/min, respectively). Accordingly, the ingestion of glucose+fructose in a solid bar (1.55 g CHO/min) was demonstrated to be oxidized at high rates (1.25±0.15 g/min), comparable to a solution (1.34±0.27 g/min). A comparison of CHO ingestion (1.5 g/min) during cycling and running at the same relative, moderate-intensity (~60% exercise-specific VO\(_2\)max) resulted in similar exogenous CHO oxidation rates (1.25±0.10 g/min vs 1.19±0.08 g/min, respectively). The present thesis also tested the gastrointestinal (GI) tolerance of high CHO ingestion rates (1.4 g CHO/min), previously recommended to athletes. High intakes in the form of a glucose+fructose gel were, on average, well tolerated during a 16-km run, and there was no difference between tolerance of glucose and glucose+fructose gel. A questionnaire-based field study of 221 athletes during prolonged endurance events (running, cycling and triathlon) revealed that voluntary CHO intake rates vary greatly between events and individuals (6-136 g/h). High CHO intakes were related to increased scores for nausea and flatulence as well as to better performance. GI distress during all studies was correlated with a reported history of GI distress. Findings from those studies suggest a need for more individualized nutritional advice that optimizes CHO and fluid delivery to enhance performance, while minimizing GI discomfort

Research has suggested that a reduction in respiratory chemosensitivity with age could be linked with a greater occurrence of sleep disordered breathing (SDB) in elders. However, it remains unclear whether this reduction is mediated by the central or peripheral chemoreceptors. Study 1 used a novel approach with a multi frequency binary sequence test to demonstrate a reduction in central chemosensitivity with age. Ageing is also associated with a fragmentation of sleep and sleep loss. Studies 2 and 3 demonstrated attenuations in central chemosensitivity following three consecutive nights of sleep loss and a night of sleep fragmentation, respectively. These alterations in chemosensitivity were similar in nature to those shown in study 1. These comparable observations and a possible mutual mechanism for them, led to the novel conclusion that age associated sleep disruption may contribute to the changes in chemosensitivity seen in older individuals. These findings may have a bearing on the development of SDB in the older generation. Lastly, pulmonary hypertension can occur in tangent with SDB and research has suggested that its occurrence is greater in older individuals suffering from SDB. Study 4 demonstrates a possible mechanism for this association, in a greater hypoxic pulmonary vasoconstriction response in older individuals.