Stimulating muscle metaboreceptive afferents alone via post exercise circulatory occlusion (PECO) typically does not result in hyperpnea in healthy humans. However ventilatory responses have been observed if metabolite accumulation is great enough (e.g. in diseased states) or during a concurrent hypercapnia-induced chemoreflex, suggesting a possible synergistic interaction. This thesis investigated the ventilatory responses to interactions between muscle afferent feedback and potentially synergistic inputs. It was firstly observed that muscle metabo/mechanoreflex activation (via PECO and passive muscle stretch, respectively) increases ventilation but only during acute hypercapnia. Additional investigations suggested that these ventilatory responses were caused by a central interaction, possibly between the medullary input from muscle afferents and central chemoreceptors. Secondly, experimental augmentation of the muscle metaboreflex enhances the ventilatory response during exercise, but not during PECO, suggesting interactions between the metaboreflex and other inputs activated in exercise. Lastly, PECO caused increased ventilation in COPD patients but this was unrelated to chronic hypercapnia. Collectively these findings suggest that in health, muscle metabo/mechanoreflex stimulation induces ventilatory responses, but their effects only appear to be unmasked in combination with secondary synergistic inputs. However, when the metaboreflex is powerful enough, arguably such as in COPD, ventilatory responses to metaboreceptor stimulation alone can be observed.

Background Cervicobrachial pain is a painful condition which, when chronic, might lead to high levels of disability. Limited data from small studies have reported that the lateral glide mobilisation is effective on reducing pain in the short-term. The primary aim of this study was to establish whether the lateral glide mobilisation technique was effective in reducing pain in the long-term. Methods Literature reviews on cervicobrachial pain provided the rational to conduct a phase III trial. An audit and a preliminary study were used to inform methods for the trial. A single-centre randomised clinical trial was conducted on participants with chronic cervicobrachial pain. Participants were randomised to receive either the lateral glide with self-management or self-management alone. The trial was powered to detect a between group difference of 20mm on worst pain on a visual analogue scale (VAS) at 52 weeks follow-up. Results Ninety-nine participants were recruited to the trial. There was a non-significant between-group difference for mean VAS(worst pain) scores at 52 week follow-up (p=0.52; 95% CI -14.72 to 7.44). Conclusion The findings from this trial provided no evidence that the lateral glide was more effective than a comparator in the management of chronic cervicobrachial pain in the long-term.

Rheumatoid arthritis (RA) is a chronic inflammatory condition with poorly understood pathophysiology and increased cardiovascular risk. The mechanisms for increased cardiovascular risk are not fully known, however one novel mechanism explored in this thesis is autonomic nervous system (ANS) dysfunction. The thesis comprises of: a systematic literature review; two case-control studies (n=30 RA patients, n=34 controls; a longitudinal case-study (n=1 RA patient)); a cohort study (n=112 RA patients); and a randomised placebo controlled crossover study (n=10 healthy controls). The work presented in this thesis demonstrates that ANS dysfunction is prevalent in ~60 % of RA patients and characterised by heightened sympathetic outflow to the peripheral vasculature (determined by muscle sympathetic nerve activity using microneurography), depressed baroreflex control of heart rate (determined using the modified Oxford technique), depressed heart rate variability and heightened vascular responses to stressors (cold pressor test and mental stress). Inflammation was associated with ANS dysfunction, and may well contribute to the increased cardiovascular risk seen in RA. Further studies are required to: confirm these findings; determine whether therapeutic strategies to restore ANS function improve prognosis in RA; and further explore the precise mechanisms by which inflammatory cytokines may influence ANS function in health and disease.

This project investigated the effect of β2-adrenergic receptor (β2-AR) stimulation on the function of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells in vitro. Catecholamines have been previously shown to increase efflux of these cells into the blood, but the effects on cell function are unclear. In this thesis three aspects of function have been addressed. The results of the studies presented in this thesis showed that: (1) β2-adrenergic stimulation by salmeterol reduced the percentage of IFN-γ producing CD4+ and CD8+ T cells activated by Staphylococcus Aureus enterotoxin type B (SEB) superantigen, cytomegalovirus lysate (CMV) or CMV pp65 (pp65) recombinant protein. (2) salmeterol, at high concentrations, increased rolling behaviour and decreased stationary behaviour of peripheral blood lymphocytes (PBLs) on human microvascular cell line (HMEC-1) and on vascular cell adhesion molecule-1 (VCAM-1), in both flow and static assays. (3) adrenergic stimulation impaired the activation and cytotoxic function of CD8+ T and NK cells, as indicated by lower expression of CD107a (a marker of CD8+ T and NK cell activation and function) following incubation of peripheral blood mononuclear cells (PBMCs) with human erythromyeloblastoid leukemia (K562) cell line or MHC class I chain-related gene A (MICA*009) transfected Chinese hamster ovary cells (T-CHO) was analysed. The results presented in this thesis showed that adrenergic stimulation influences a number of cellular functions, such as those related to migration, cytokine production and cytotoxic function. Together the above studies may contribute to our understanding about how stress affects the ability of the cytotoxic cells.

The purpose of this thesis was to (1) examine the psychological morbidity associated with atrial fibrillation (AF), and (2) determine the effects of acute mental and postural stress, and hydration status on indices haemorhelogy, endothelial function, and platelet reactivity. Symptoms of depression (BDI scores > 10) persisted in 38% of patients with AF, with elevated state and trait anxiety (STAI score >40) being reported in 28% and 38% of patients, respectively. No significant differences in depression, state anxiety, and QoL were observed between AF and hypertensive patients; however, AF patients displayed higher levels of trait anxiety. Multiple regression analysis demonstrated baseline depression scores provided the best independent prediction of future QoL. Acute mental and postural stress yielded significant changes in haemodynamics and haemorhelogy, in addition to increasing biomarkers of endothelial dysfunction and platelet reactivity. Increased hydration status reduced blood pressure and markers of endothelial perturbation and platelet morphology both at rest and in response to the stress tasks. In conclusion, AF patients display comparable levels of depression and anxiety to patients following a myocardial infarction. In addition, behavioural activities such as mental and postural stress may implicated in the pathogenesis of acute coronary syndromes through the development of a prothrombotic state.

Little is known about neutrophil function, an important component of innate immunity, in relation to psychosocial factors. This thesis investigated the effect of acute and chronic psychological stressors on human neutrophil function among young and older adults. The first two studies examined the effects of an acute laboratory psychological stress task on neutrophil function in young and older adults, respectively. Blood samples to determine neutrophil function were taken at resting baseline, during acute stress and during recovery. In the first study (N=40), there was an acute increase in phagocytic ability and a reduction of superoxide production associated with the stress task relative to baseline. In study two (N =17), there was a significant reduction of neutrophil superoxide production associated with the stress task. Study three (N=48) examined the effect of chronic stress, a recent bereavement (<2 months), on neutrophil function in elders. Cortisol and dehydroepiandrosterone-sulphate (DHEAS) levels were determined in serum to assess potential mechanisms. Superoxide production was significantly reduced among the bereaved group when challenged with E. Coli; also, the bereaved had a significantly higher cortisol:DHEAS ratio compared to controls. Overall, this thesis shows that human neutrophil function is sensitive to both acute and chronic psychological stress exposures; however, more research is needed to determine the specific underlying mechanisms behind the observed alterations.

Undertaking physical activity in the presence of a natural environment (termed green exercise) is good for health and wellbeing. Nevertheless, we need to understand more about what motivates people to perform green exercise. The literature suggests that beliefs may play a role in physical activity behaviours and outcomes. To expand on this, the aim of this thesis was to explore the role of beliefs on green exercise behaviours and outcomes. Specifically, the following research questions guided the experimental chapters: Do beliefs predict visiting local green space? Can beliefs be modified to encourage more green exercise, and improve outcomes? Chapter 2 found that subjective measures were stronger predictors of green exercise than quantity of local green space, showing initial support for subjective measures playing a role in green exercise behaviours. To explore this further, questionnaires to assess beliefs were developed (Chapter 3) and tested (Chapter 4). This was important because previous research has not explored what people think about green exercise. The evidence showed that beliefs about green exercise appear to predict intentions to perform green exercise and visit frequency to local green space. Chapter 5 used indoor vs outdoor methodology to assess the impact of a promotional video (attitude modification intervention) on the psychological outcomes of green exercise. This was important because assessment and/or modification of attitudes in a green exercise environment had not been previously examined. Chapter 6 used a promotional video in a four-week green exercise intervention. Overall, the evidence was mixed, however, there was some indication of expectancy effects. Regular green exercise can help with health and well-being. Evidence provided in this thesis highlights the importance of subjective measures (such as perceptions, beliefs, and intentions) on green exercise behaviours and acute psychological benefits.

Elite youth soccer player’s performance depends on a multitude of factors (Stølen et al. 2005). Muscular force production capability is of likely importance due to the frequency of powerful actions that occur within match play (Faude et al. 2012). Little is known though of the training undertaken at elite youth soccer academies to increase muscular force production capabilities particularly across maturation groups. There is also little evidence around the nature, or genetic influence on this variable in these populations. Greater knowledge on these areas would be beneficial to aid an understanding of performance and to plan practical interventions. Eight weeks of training for players in the under 9 (U9) through to under 21 (U21) age groups (Chapter 3) were recorded to investigate the duration of each training type completed. The total training duration increased from U9 to U14 before reducing at U15 and then remaining unchanged through to, and including, the U21 age group. Soccer training accounted for 97 ± 4 % of session time in the U9 to U14 groups and 74 ± 3 % in the U15 to U21 groups. The remainder of training was made up of work that was not soccer based. The data in this case study suggest that training time is focussed on the technical/tactical development throughout the academy, particularly in the younger age groups. Study 2, part A (Chapter 4) provided baseline isometric maximal voluntary force (MVF) data for players and an maturation-matched non-elite control group. MVF was slightly higher in the elite compared to control cohorts during an isometric mid-thigh pull (IMTP, 118.29 ± 13.47 N compared to 109.69 ± 17.00 N). Such data may indicate that ability to produce force, specifically isometric MVF, may not be a crucial determinant of performance in elite youth soccer based on this sample. The purpose of study 2, part B (Chapter 4) was to establish the effect of 8 weeks typical training on elite youth soccer players’ IMTP MVF. This was also compared to a non-elite control cohort matched for maturation status and not undertaking training. Isometric MVF did not change in either group over the 8 week period (P = 0.386). These data suggest that this elite youth soccer training simply maintained current strength levels and was not sufficient to elicit increases in isometric MVF. Study 3 (Chapter 5) examined variations in four separate genes, all identified as potentially having an influence on muscular force production capabilities: PPARA rs4253778, NOS3 rs2070744, COLIA1 rs2249492 and VDR rs2228570. Allele and genotype frequency was determined along with the influence of those single nucleotide polymorphisms (SNPs) on isometric MVF. Only NOS3 was different in genotype distribution between cohorts with TT genotype showing 45.0 % and 30.4 % frequency in elite and control cohorts respectively (P < 0.001). Furthermore, no difference was seen between cohorts for isometric MVF data when comparing influence of any genotypes of any gene. These data provide novel information around genotype frequency in this population and would suggest that the gene variations examined here might not play a role in force production in these populations. Overall, these findings suggest that muscular force production may be important for elite youth soccer performance, but that current training practices to improve this characteristic should be revised. This seems especially relevant given the lack of genetic association with force production in the gene variations examined here, i.e. elite youth soccer players do not appear to be selected based on a genetic predisposition for greater isometric force production capabilities.

Introduction: Rugby is a professional sport which places emphasises on strength, power, speed and endurance. Therefore the accurate assessment of rugby performance is very important for sports and exercise therapists to enable peak performance for the players. Lower limb strength is often tested by means of isokinetic testing, whilst functional power is tested by means of the vertical jump test. Sophisticated equipment used in the measurement of performance indicators, are often not available in smaller communities and rural areas. A good correlation between laboratory testing and functional testing could be of great value for determining performance in less fortunate communities. Aim of Study: To determine the relationship between isokinetic strength testing of the quadriceps and hamstring muscle groups and vertical jump performance in rugby players. Methods: Fifty one male, rugby players who were part of the Varsity Cup Tournament in (2011) participated in this study. Ethical approval was given by the Human Research Ethics Committee (HREC) of the University of Witwatersrand. Height and weight were measured. Isokinetic knee extensor and flexor strength was tested (Biodex system 4 dynamometer TM ) at 60˚/sec (5 repetitions), 180˚/sec (10 repetitions) and 300˚/sec (15 repetitions). A single leg vertical jump was done using the Vertec and the performance was assessed as maximal height jump in centimetres. Descriptive statistics (mean and standard deviation) are reported for all outcomes. The SPSS software (IBM. SPSS version 21) was used for analysis. A Pearson's Product Moment Correlation coefficient was calculated between the isokinetic parameters of quadriceps and hamstring muscles and the vertical jump height and power (watts). An independent t-test and a paired t-test were used to calculate the differences between the forward and backline players and the dominant (Dom) and non-dominant (ND) legs. Results: The mean age of the participants was 21.4 ± 1.2 years; they were 1.83 ± 7.4m tall and weighed 99.3 ± 13.8kg. There were 26 forward players (mean height of 1.88 ± 7.2m and mean weight of 109.9 ± 10.3kg) and 25 backline players (mean height of 1.80 ± 5.5m and mean weight of 88.3 ± 6.1kg). The forwards were significantly taller and heavier than the backline players (p = 0.0001). The forwards produced significant greater peak power in the vertical jump than the backline players in both the dominant and non-dominant legs (p=0.0001). The PT (Nm) decreased as the angular velocity increased from 60˚/sec to 300˚/sec. A significant negative correlation (r = - 0.313; p = 0.025) between peak torque (PT) concentric strength from the hamstrings at 60º/sec and the vertical jump height on the non-dominant side were found. Quadriceps PT to vertical power at the higher velocities showed significant correlations at 180º/sec (dominant: r = 0.294; p = 0.011) and 300º/sec (dominant: r = 0.352; p = 0.011; non-dominant: r = 0.293; p = 0.037). No significant correlations were found between peak torque and vertical jump height when corrected for body weight. When correlating PT and vertical jump power corrected for body weight significant negative correlations was found at 180º/sec (dominant: r = 0.319; p = 0.022; non-dominant: r = 0.305; p = 0.030) for the hamstrings. Conclusion: The findings from the presented study found no significant correlation between lower limb isokinetic knee muscle torque parameters and vertical jump performance in rugby union players. Future research should investigate the relationship between isokinetic testing and vertical jump height by including the parameters of a multi joint mechanism.

Non-specific chronic low back pain has serious personal and socio-economic consequences. International guidelines recommend multimodal cognitive behavioural management (CBT). The effectiveness of CBT might be enhanced by directly targeting central nervous system pain processing. Transcranial direct current stimulation (tDCS) is a novel approach aiming to influence pain by altering cortical excitability. An evaluation of existing reviews indicated the need for an up-to-date review of clinical and experimental pain trials. A systematic review including 14 trials (published 2006-2012) evaluating tDCS for the reduction of clinical and experimental pain identified a low level of evidence for its effectiveness. Only 1 trial had a low risk of bias. A meta-analysis of trials on clinical pain identified a small pain reducing effect that just reached clinical importance. To investigate the effectiveness of tDCS alone and in combination with CBT, a double-blind RCT was conducted; preceded by a feasibility study confirming practicability of trial procedures and patient acceptability of tDCS. Results indicated that tDCS alone or in combination with CBT did not significantly influence pain or disability. An updated meta-analysis, including this trial’s results, lowered the pain reducing effect of tDCS below clinical importance, and increased the level of evidence for its effectiveness to "high".