Fatigue is a universal phenomenon with functional and perceptual consequences. The study of fatigue in the exercise sciences has historically focussed on factors that limit performance during exercise. More recent proposals have shifted the focus of this understanding to examine how intensity is regulated during exercise through the study of the pacing strategy, which has both physiological and practical consequences. The aim of this thesis was to investigate the biological basis of self-pacing and the optimum pacing strategy for endurance time-trial events. Study 1 assessed the reproducibility of the pacing strategy and the consistency of the performance, perceptual and physiological response during self-paced time-trial exercise in well-trained cyclists. This study demonstrated the existence of a global pacing strategy that was reproducible on repeat 20 km cycling time-trials (TTs), and consistent between 4, 20 and 40 km TTs. The performance, perceptual and physiological response was also reproducible, confirming the feasibility of studying manipulations of the self-pacing strategy and the subsequent impact on these variables. Studies 2 and 3 adopted a model whereby participant’s best self-paced TT performance was used to set time- and work-matched exercise bouts to study the effect of even- and variable-pacing. These studies revealed that a variable-pacing strategy that contains frequent periods of high-intensity exercise resulted in an augmented physiological response and higher perception of exertion compared to time- and work-matched even- and self-paced exercise. Conversely, even-pacing resulted in attenuation in the metabolic and perceptual cost of the bout, but only when the self-selected pacing strategy was sub-optimal. When self-pacing was optimal, time- and work-matched even-pacing resulted in cumulative metabolic stress that caused early exercise termination. In study 4 the biological basis to fatigue during 4, 20 and 40 km TTs was assessed. This study demonstrated that the contribution of central and peripheral mechanisms of fatigue during self-paced exercise is task-dependent. Specifically, the shorter, higher intensity 4 km time-trials were characterised by a greater degree of peripheral fatigue and less central fatigue compared to longer, lower intensity 20 and 40 km time-trials where less peripheral and more central fatigue was observed. The supraspinal contribution to fatigue was alsomgreater during longer TT exercise. These studies have provided novel insight in to the biological factors that underpin the regulation of self-paced exercise, and the optimum pacing strategy for endurance TT events.

The purpose of this thesis was to explore the role of exercise induced blood flow haemodynamics in the cardiovascular adaptations associated with isometric exercise training, with focus on resting blood pressure adjustment in normotensive participants. Using a cross-sectional study, it was identified that significant relationships were present between (i) blood flow, (ii) shear stress, and (iii) shear pattern responses (measured in the femoral artery), during and immediately following isometric bilateral leg extension exercise of increasing intensity. Based on these findings, it was feasible to suggest that the haemodynamic response to high intensities of acute isometric exercise might provide a physiological challenge to the cardiovascular system, that upon repeated exposure via isometric exercise training, may induce cardiovascular adaptation and resting blood pressure reductions. Subsequent to this, a randomised controlled trial established that performing isometric exercise training to a ‘high haemodynamic stimulus’ did not induce significantly greater adaptation in resting blood pressure than when performing isometric exercise training to a ‘low haemodynamic stimulus’ or control. When the training group (high and low combined) were compared to the control, significant reductions in resting blood pressure were observed. Furthermore, non-invasive cardiovascular variables that were considered as possible physiological mechanisms for resting blood pressure adaptation following isometric exercise training did not correlate with within group resting blood pressure changes. Whilst these findings suggest that a haemodynamic challenge may not be the primary stimulus responsible for inducing resting blood pressure adaptation following isometric exercise training, these results do demonstrate the effectiveness of isometric exercise training for potential health gains via reductions in resting blood pressure in normotensives. Importantly, these findings have progressed the current understanding surrounding isometric exercise training induced resting blood pressure reductions and will allow future research to narrow their focus upon other physiological variables that may be the stimuli for blood pressure adaptation.

The aims of this research programme were to a. Further examine and develop an existing self-report measure of Challenge and Threat within a sport context, b. Examine Challenge and Threat self-report with performance in a sport context, c. Further examine the Biopsychosocial Model (BPSM) proposed in relation to Challenge and Threat and sport performance, d. Examine the associations between Challenge, Threat, cortisol response and sport performance, e. Examine self-report of emotions direction and intensity experienced during a sport performance in regard to Challenge and Threat and f. Examine Challenge and Threat in combination with each other in regard to sport performance. These 6 aims were addressed in 3 different empirical studies. Study 1 used a cross sectional study design to explore the validity and reliability of an existing self-report measure of Challenge and Threat. Participants were gym users (n=200, Mage=24.91) and asked to complete the self-report measure before a dart-throwing competition. Study 2 comprised of three different stages. Stage 1; a cross sectional study design to examine the content validity of a pool of existing self-report items to measure Challenge and Threat in a range of athletes (n=25, Mage=22.00). Participants comprised of male and female athletes engaged in various sports (football, n=6, cricket, n=2, swimming, n=5, tennis, n=1, rugby, n=6, netball, n=3, basketball, n=2.). Stage 2, used a cross sectional study design to further examine the construct validity of the remaining items from stage 1. This stage used principle components analysis (PCA) to determine whether Challenge and Threat self-report items were grouped in a particular way (Kline, 1994). Participants were competitive runners (n=197, Mage=37.11) and asked to complete the self-report measure regarding Challenge and Threat before competition. Stage 3 used a cross sectional study design to explore the validity and reliability of the self-report measure of Challenge and Threat developed in stages 1-2 in competitive runners (n=147, Mage =30.06), using confirmatory factor analysis (CFA) to examine how well the data total fitted the proposed hypothetical model. Finally a quasi-experimental study (study 3) examined the association between Challenge and Threat and shooting performance. This study explored the Challenge and Threat self-report measure and its relationship with performance, emotions and physiological responses. Participants in this study comprised of university student and staff members (n=102, Mage =27.11). Results from study 1 suggested that the existing self-report measure of Challenge and Threat utilised was not suitable for use within a sport context. Results from study 2, stage 1, revealed a pool of self-report items that athletes described as applicable and relevant to their sports performance. Results from study 2, stage 2, suggested that items identified in study 2, stage 1 represented a two component solution, one associated with Threat and the other Challenge. Results from study 2, stage 3 suggested that a 12 item self-report measure was suitable for use within a sport context and that Challenge has a positive association with sport performance. Finally, study 3, suggested that the self-report measure of Challenge and Threat developed in study 2 (stages 1-3) was suitable for use within a sport context. Results from study 3 also suggest that a mixture of Challenge and Threat can have implications for performance outcome. Emotions reported were shown to have associations with Challenge and Threat self-report, as suggested by The Theory of Challenge and Threat States in Athletes (TCTSA). The study findings showed that physiological associations with Challenge and Threat were equivocal. Limitations to the present research programme and directions for future research are discussed.

The main focus of this thesis was to develop an accessible home-based isometric exercise training (IET) protocol for the reduction of resting blood pressure (BP). Hypertension is estimated to affect nearly 30% of the world’s population (WHO, 2012) and represents an inordinate health and economic burden worldwide. A growing body of research suggests that IET can lower resting BP. However, the majority of studies have utilised expensive and/or laboratory-based equipment, which may not be accessible to the general population. To this end, the studies within this thesis explored whether the novel isometric wall squat exercise could be prescribed for home-based training using relatively simple, inexpensive equipment. The first study determined a method for adjusting the wall squat intensity. It was found that knee joint angle reliably produced inverse relationships with heart rate (HR) and BP when individual bouts of wall squat exercise were completed (r at least -0.80; P < 0.05). Study 2 then established that these inverse relationships could be replicated from completing an incremental test (r at least -0.88; P < 0.05), from which wall squat training intensity could then be prescribed at an individualised knee joint angle (104 ± 7°) to elicit a target training HR (95% peak HR: 121 ± 14 beats∙min-1). Finally, using these methods, study 3 implemented a 4 week home-based isometric wall squat training protocol and found statistically significant and clinically relevant resting BP reductions (systolic BP: -4 mmHg; diastolic BP -3 mmHg; mean arterial pressure: -3 mmHg). These results support the majority of previous research that has found reductions in resting BP following IET. Furthermore, the primary BP control mechanisms were also explored and the results suggested that a reduction in resting BP was potentially mediated by a decrease in resting cardiac output (-0.54 ± 0.66 L∙min-1), which may have been governed by a reduction in resting HR (-5 ± 7 beats∙min-1). The novel home-based IET protocol developed within this thesis may be more time and cost effective, which may ultimately increase the adherence to and efficacy of IET for the reduction of resting BP.

For patients with type 1 diabetes, a fear of hypoglycaemia and a concern over a loss of control with wider diabetes management are the most salient barriers to exercise participation and adherence. A large proportion of patients report a lack of advice for preventing post-exercise hypoglycaemia, and many feel largely uninformed about insulin administration and carbohydrate intake around aerobic-based exercise. Presently, recommendations within the literature are based predominantly on anecdotal and observational, but not empirical or interventional data. Therefore, this thesis aimed to develop a strategy that enables patients to effectively self-manage glycaemia following exercise, supported by evidence pertaining to the deeper physiological implications and consequences. Study one (chapter 3) revealed that under conditions of reduced pre-exercise rapid-acting insulin dose, it is also necessary to reduce post-exercise rapid-acting insulin administration by 50% to prevent early-onset hypoglycaemia (≤ 8 hours post-exercise). Consequently, some patients experienced post-prandial hyperglycaemia with this intervention, although this was not associated with any other metabolic, counter-regulatory hormonal, or inflammatory disturbances. The results of study two (chapter 4) demonstrate that post-exercise meal composition, under conditions of reduced pre- and post-exercise rapid-acting insulin dose, carry important implications for post-prandial glycaemia. Specifically, consumption of low GI post-exercise carbohydrates normalise post-prandial hyperglycaemia, whilst protection from early onset hypoglycaemia is maintained. In addition, post-exercise meal composition heavily influences inflammatory markers; a high GI meal results in a pronounced inflammatory response, but a low GI meal completely prevented any rise in measured inflammatory markers. Lastly, study three (chapter 5) assessed the efficacy of a combined basal-bolus insulin reduction and low GI carbohydrate post-exercise feeding strategy. A 20% reduction in basal insulin provided full protection from hypoglycaemia for a total of 24 hours after exercise. Furthermore, ketonaemia did not increase to clinically meaningful levels, nor did inflammatory markers rise above concentrations seen at rest or when exercising under usual basal dose. No other metabolic or counter-regulatory hormonal disturbances were observed following a combined dose reduction to basal-bolus insulin and low GI carbohydrate post-exercise feeding. Collectively, this thesis has shown that acute prandial adjustments in rapid-acting insulin and carbohydrate feeding, in combination with alterations in basal dose, are effective for managing post-exercise glycaemia and protecting patients from hypoglycaemia for a total of 24 hours after exercise. Moreover, this strategy aims to maintain euglycaemia by reducing post-prandial hyperglycaemia. This is not associated with clinically significant rises in ketonaemia, nor does it induce inflammatory, counter-regulatory hormonal, or other metabolic disturbances. Clinicians are advised to tailor these recommendations to a patient’s individual exercise preferences, fitness and exercise ability, level of diabetes management, and treatment regimen.

Combining strength and endurance training within the same regimen is aptly referred to as “concurrent training”. Research conducted over the previous 3 decades has indicated concurrent training can result in attenuated development of strength, power and hypertrophy when compared to strength training in isolation. Despite extensive research the mechanisms contributing to this so called “interference effect” are yet to be fully elucidated, as is the influence of manipulating acute training programme variables within a concurrent regimen. As such, the purposes of this thesis were to investigate and draw conclusions regarding underlying physiological mechanisms relating to the interference effect. Additionally, this thesis sought to examine the effects of manipulating programme variables, including frequency and sequencing of exercise within concurrent training regimens on strength related adaptation. The findings of this thesis indicate overall training volume and frequency of endurance training within a concurrent intervention influences the presence and magnitude of the inhibition of strength development. Concurrent training volumes of 3 d·wk-1 elicited muted strength development, whereas lower frequencies did not. Whilst interference was not attributable to neuromuscular factors, it was reported that cortisol was only elevated following higher training frequencies, indicating training stress and catabolism may contribute to interference. Additionally, the sequencing of strength and endurance training can influence endocrine and signalling responses associated with strength adaptation, and it appears strength prior to endurance elicits greater increases in growth associated signalling. The findings of this thesis indicate that overall training stress influences the presence and magnitude of interference experienced, and is reflected in catabolic endocrine responses. Additionally, strength prior to endurance training promotes more favourable anabolic signalling than vice versa, which over time may contribute to greater strength type adaptations.

Since being introduced in the late 1990’s, enhancing recovery after surgery (ERAS) protocols have been promoted for inclusion in the care pathway for colorectal cancer patients scheduled for resection surgery (Gustaffson et al., 2012). This multimodal approach to stress management is thought to reduce the amount of surgical stress encountered; attenuating the debilitating effect surgery has on the patient and aiding subsequent recovery with a reduction in hospital length of stay reported (Lv et al., 2012). Although not currently included in ERAS, a period of pre-operative exercise training, known as PREHAB, has been proposed as a potential mechanism of improving the patient’s pre- operative fitness ahead of surgery (Carli & Zavorsky, 2005). As no research currently exists into how feasible it would be to incorporate a period of PREHAB into the current NHS colorectal cancer care pathway in the United Kingdom, this thesis aimed to address this gap in the literature as well as investigate whether participation in PREHAB would alter physical functioning and health related quality of life (HRQOL) prior to surgery and improve post-operative recovery. The impact of PREHAB on upregulating the body’s heat shock protein (Hsp) and glutathione defence systems was also explored. The purpose of the first experimental chapter was to investigate through a questionnaire-based approach whether an interest in the potential use of PREHAB existed in the Hull and East Riding area and what were the perceived benefits and barriers to participation. Over 75% of respondents indicated they would be interested in PREHAB if awaiting surgery although a lack of time (62% of respondents), cost (46%) and work responsibilities (43%) were identified as the main barriers to participation. Having established an interest existed in PREHAB, the test-retest reliability and measurement error of the five tests of physical functioning (Timed up and go [TUG], five times sit to stand [FTSTS], 5 step stair climb [SCT], handgrip dynamometry [HGD] and 6 minute walk test [6MWT]) that would be used to assess the effectiveness of the PREHAB intervention was investigated. All five tests displayed excellent test-retest reliability (all ICCs: >0.90) with the standard error of measurement and minimum detectable changes at 95% as a percentage of the mean ranging from 2.3% to 5.2% and 6.3% to 16.1% respectively. In the third experimental chapter, a randomised controlled pilot trial investigating a novel PREHAB intervention based on the joint-by-joint approach to training was conducted in colorectal cancer patients. The ineligibility of 43% (84 out of 198) of patients due to insufficient time to scheduled surgery (< 2 weeks) and subsequent poor consent rate of eligible patients (18.4%; 21 out of 114 patients) indicates implementing PREHAB into the current colorectal care pathway would be difficult. However, improvements in TUG, SCT and 6MWT performance were observed in all nine patients randomised to PREHAB (all p < 0.05), a result not replicated in the control group (improved performance at reassessment: TUG: 2 out of 9; SCT: 3 out of 9; 6MWT: 4 out of 9). This suggested that despite the limited time from recruitment to surgery (median PREHAB period: 23 [IQR: 14] days), the PREHAB programme was sufficient to improve physical functioning in these patients. There was however no significant difference in length of hospital between the two group (Control: 8 [5] days; PREHAB: 10 [7] days). In the final two experimental chapters, the effects of the PREHAB intervention on basal Hsp72 and Hsp32 expression and the glutathione defence system was explored although the low recruitment rates previously described limited the results. No changes were evident in Hsp32 or Hsp72 expression; or in total glutathione or GSH/GSSH ratio for either group during the pre-operative period. There was a potential time of day effect for monocyte Hsp72 as expression decreased in 13 out of 16 at pre-operative reassessment (p < 0.05) thus potentially masking any adaptations to have taken place. Furthermore, attempts to establish whether PREHAB altered Hsp72 inducibility were not possible due to inadequate viable samples being available. Given the limited sample size, definite conclusions were difficult to make although it was plausible the absence of change in Hsp72, Hsp32 and glutathione following PREHAB was due to insufficient stimulus being present given the often low to moderate intensity of the intervention. The findings of this thesis highlighted the issues regarding the limited time available in the pre-operative period that would need to be overcome in order to practically implement a PREHAB intervention into the current NHS colorectal cancer care pathway. Despite this, the improvements observed in physical functioning following PREHAB suggests if the intervention could be adapted to a cost-effective home-based programme it may be a viable addition to the ERAS programme.

The issue of career transition in and out of sport has received increasing attention from researchers over the past three decades (e.g. Fortunato & Marchant, 1999; Lavallee, 2005; Park, 2012; Ryba, Stambulova & Ronkainen, 2016). However, there continues to be a paucity of research exploring the impact of ‘others’ on athletes’, or indeed former athletes’ transitional experiences. Therefore, an aim of this study was to provide a relational, emotional and socio-cultural analysis of former professional footballers’ multiple transitional experiences and, in particular, to how interactions and relationships with significant ‘others’ impacted upon their transitions. Data were collected through a series of in-depth, semi-structured, interviews with three participants alongside my own auto-ethnography. Throughout the study, the collection, analysis, and representation of data were features of an ongoing, reflexive, and iterative process (Tracy, 2013). Here, the analysis comprised of both emic and etic readings of the data which gave me the opportunity to explore emerging themes and issues in both future writings and in subsequent interviews (Sparkes & Smith, 2002). In keeping with my interpretive stance, the findings were principally understood in relation to Bauman’s (2012) liquid modernity, Crossley’s (2011) relational sociology, May’s (2013) sense of belonging, and Burkitt’s (2014a; 2014b) discussions of emotions and social relations. The work of Turner and Stets (2005) and Cooley (1964[1902) was also used to make sense of the emotions I experienced throughout my auto-ethnographic research. My analysis revealed that the participants understood their transitions through their interactions and relationships with a variety of significant others who played important roles in both decision-making and sense-making processes. Here, each transitional experience (both inside and outside of football) affected, and was affected by, the participants’ location in various networks of interaction. This was also evidenced in my own transition(s) as I approached the end of my playing days in (semi-) professional football where my emotions were also inextricably linked to my multiple identities and therefore multiple networks of social relations.

There are evidence that high-intensity acute exercise can promote oxidative stress. High-intensity intermittent exercise (HIIE) is a type of structured physical training characterised by repeated bouts of high-intensity exercise interspersed by recovery periods. As the impact of intermittency during acute HIIE has not been extensively studied, it is possible that the repeated intensive bouts within HIIE could induce oxidative stress levels. Plasma biomarkers, including lipid hydroperoxides and markers of DNA damage, have been increasingly applied within acute exercise physiology research to measure oxidative stress. This thesis presents the experimental outcomes of research into the effect of different forms of HIIE on established and novel biomarkers of oxidative stress. For the 1st study (chapter 3) a liquid chromatography-mass spectrometry (LCMS) method was developed and optimised to measure DNA oxidation in plasma samples. Implementing a range of progressive analytical techniques, the method developed had a sensitivity to detect 8-hydroxy-2'-deoxyguanosine (8-Oxo-dG) in human plasma samples in the range of 5 – 500 nM. The implementation of this LC-MS method along with other oxidative stress biomarkers was thereafter applied to a randomised investigation of different high-intensity intermittent exercise protocols. The 2nd (chapter 4) and 3rd (chapter 5) studies considered the effect of different forms of intermittent exercise undertaken by 9 healthy, regularly active male participants (aged 21.0 ± 3.0 years). Each intermittent exercise session was performed for a total duration of 45 minutes. Each 45 minute exercise protocol consisted of 4 minute stages of high-intensity intermittent running at a mean 75% v!O2max, followed by 1 minute of passive recovery (halt of running). The experimental protocol was specifically designed to match for average speed, duration and distance but varied in either the intermittency (chapter 4) or the acceleration/deceleration (chapter 5). The effects of different forms of intermittent exercise (high, moderate, low) or different acceleration/deceleration components (high, moderate, low) in relation to oxidative stress biomarkers were determined. Results showed the absence of significant increases in all the biomarkers examined. However, significant variation in individual oxidative stress responses was observed. Within a final study, the 8-Oxo-dG method developed was compared to a widely used ELISA method, as there are indications in the literature that ELISA may overestimate 8-Oxo-dG. Determination of 8-Oxo-dG was undertaken on blood plasma samples from 30 chronic heart failure patients (males = 23, females = 7) recruited from the Academic Cardiology department at Castle Hill hospital, Hull, UK, as previous studies have characterised the heart failure syndrome to be associated with higher levels of oxidative stress. Results showed that the LC-MS method developed found no detectable levels of 8-Oxo-dG in plasma samples whereas ELISA showed quantifiable amounts of 8-Oxo-dG. Thus, this thesis presented that the impact of intermittency or acceleration/deceleration following acute HIIE does not induce significant oxidative stress as determined by plasma and serum biomarkers, including plasma 8-Oxo-dG.

Endothelial microparticles (EMP) offer an insight into the state of the endothelium and are known to be elevated in diseases characterised by endothelial dysfunction (ED) (Horstman et al., 2004; Vince et al., 2009a). EMP have also been shown to increase after exercise/endothelial stress in healthy individuals (Sossdorf et al., 2011; Vince et al, 2009) but this area remains relatively novel. The purpose of the first experiment was to quantify the effects of an acute bout of strenuous exercise on the circulating levels of EMP and to assess if this effect is different after the ingestion of an extensively researched ergogenic aid (sodium bicarbonate, NaHCO3). Seven physically active and apparently healthy males volunteered to perform 10 x 15 second (s) cycle sprints after the ingestion of either 0.03 g.kg.BW−1 NaHCO3 or 0.045 g.kg.BW−1 of a placebo (sodium chloride, NaCl) in capsules. The ingestion of NaHCO3 induced a pre exercise alkalosis as evidenced by a significantly altered resting acid base status, but had no influence on levels of EMP in healthy males. As a result, the data was combined for the two experimental groups, and the exercise produced a significantly increased level of CD105+ MP (MP; microparticles) at 90 minutes (min) and 180 min when compared with resting levels (p = 0.010, p = 0.043 respectively). The observed peak value at 90 min was also significantly greater compared to immediately post exercise (p = 0.019). CD106+ MP also increased significantly to 90 min from immediately post exercise (p = 0.020) and this was still greater at 180 min compared to post exercise (p = 0.015). It was concluded that exercise of this nature was sufficient to elicit ED, although the endothelium shows signs of endothelial repair within a matter of hours (hr). Also, it appears that pre exercise alkalosis has no effect on the attenuation of EMP quantity. Additional work was completed to verify the novel finding that CD105+ MP and CD106+ MP appear markers of endothelial function (EF), and to further examine the quantification of EMP, this time in healthy females. There was also an additional blood draw in order to assess where the maximum level of endothelial stress was occurring post exercise. In the second experiment, 10 healthy females completed the identical repeated sprints protocol as the first experiment, this time without the ingestion of NaHCO3. CD105+ MP were increased 90 min post exercise compared to immediately after exercise (p = 0.042). There was again a decline in both markers from 90 min to 180 min, although this was not significant. Furthermore, with the addition of a blood draw at 45 min post exercise, it was suggested that EMP levels appear to be rising between 45 min and 90 min post exercise, speculating this is the time point of greatest endothelial damage. Finally, shear stress was suggested as a key reason behind the increase in endothelial damage as a result of exercise, as indicated by significant changes in variables such as heart rate (HR) and systolic blood pressure (SBP). The third experiment employed a longer 90 min interval cycling protocol with the purpose of quantifying EF over a greater period of time, allowing investigation into whether the markers of EF were altered in the same way as the previous two experiments. It was also an aim to further assess the possible influence of shear stress factors on ED. Fourteen healthy males completed 90 min of high intensity aerobic exercise, and there were several changes in both CD105+ MP and CD106+ MP. CD105+ MP rose significantly from rest to an observed peak at 90 min (p = 0.019). Both of these markers indicated a significant restoration of the endothelium as indicated by a fall from peak values during recovery to 180 min post exercise (CD105+ MP, p = 0.009; CD106+ MP, p = 0.022). This experiment concluded that the endothelium is greatly affected by highly intense exercise over a prolonged period of time, but is recovered fully in a time period of 3 hr. The effects of shear stress again appear to be largely influential, but future work must now be conducted in order to build on the findings from this research and examine shear stress closely during exercise and its relationship with EMP quantification. It was the aim of the next experiment to investigate two separate methods of assessing EF (EMP and EndoPAT-2000), this time in a group of sedentary, but otherwise healthy individuals, in order to monitor the changes as a result of an acute bout of moderate intensity acute exercise. There were no significant differences found in EF as a result of exercise. This was indicated by no significant changes in CD105+ MP concentrations from pre to post exercise (p = 0.84) or pre to 60 min post exercise (p = 0.612). CD106+ MP concentrations showed a decrease from resting values (2513 CD106+ MP per μl platelet free plasma; PFP) to immediately post exercise (1368 CD106+ MP per μl PFP, p = 0.09), and again at 60 min post exercise (1293 CD106+ MP per μl PFP, p = 0.073) compared to resting values. Additionally, EndoPAT scores were unaffected by exercise, with values of reactive hyperaemia index (RHI) changing from rest (2.43) to post exercise (2.57), but this was not significant (p = 0.35). Correlations were carried out in order to determine and comparisons that may have existed between EMP and EndoPAT score using RHI. Although there was a slight trend for the higher numbers of CD105+ MP to correlate with the lower scores of RHI (r = 0.327) this was not significant (p = 0.171). CD106+ MP showed no correlations with RHI (r = -0.087, p = 0.717). This chapter suggested that exercise was not strenuous enough to see any significant changes in EF, and EMP continue to appear efficient markers of EF in a population of sedentary, healthy individuals. The final experimental chapter investigated the effects of a supervised 8 week moderate intensity exercise programme on women with polycystic ovary syndrome (PCOS) and control women free from any known disease. The aim was to assess if this type of exercise could improve EF in this population, and if there was a relationship with EMP (CD105+ MP and CD106+ MP) to other factors, such as body composition and cardiorespiratory fitness. EF was improved from baseline values to post exercise programme, with CD105+ MP concentrations reducing from 2113 CD105+ MP per μl PFP to 424 CD105+ MP per μl PFP (p = 0.025). Furthermore, control women showed no significant change from pre to post exercise programme in CD105+ MP (p = 0.25), or CD106+ MP (p = 0.99). Further analysis was performed to look for any associations with the changes in EMP compared to body composition changes as a result of exercise, but no significant correlations existed. This study concluded that supervised, moderate intensity exercise independent of substantial weight loss was enough to elicit an00 improvement in EF in women with PCOS compared to healthy control women. Additionally, EMP concentrations appear to be able to effectively map changes in EF across a long period of time in diseased states, adding to the notion that EMP may account for EF. Future work must now build on these findings from this research and examine this response in a larger cohort involving PCOS women with varied phenotypes and body composition.