Cell-derived microvesicles (MVs) are naturally released into the human circulation and an increase in the concentration of certain MV populations have been observed after exercise. However, the MV appearance dynamics, the exercise-related stimuli that induce their formation and physiological relevance are poorly understood. Hence, the overall objectives of this thesis were to: 1) characterise the circulating platelet (PMV) and endothelial-derived MVs (EMVs) responses during exercise and recovery, as well as their arteriovenous dynamics, 2) investigate the potential role of haemodynamic forces on MVs formation in vivo by vascular shear stress manipulations, and 3) explore the putative proliferative, chemotactic and angiogenic potential of exercise-derived MVs upon human vascular endothelial cells in vitro. Chapter 5 of this thesis describes the time-course of MV appearance in response to prolonged cycling, and demonstrates that intravascular [PMV] increases during and after exercise performed in the heavy intensity domain, whereas [EMV] remains unaltered. Moreover, [PMV] during exercise was related to estimates of vascular shear stress and plasma noradrenaline levels. Results from chapter 6 revealed that PMVs increased in the arterial circulation during passive heat stress, and in the arterial as well as venous circulation during short duration very heavy exercise engaging either a large or small muscle mass. The increases in [PMV] were not directly linked to local changes in vascular shear stress through heat stress and exercise, indicating a systemic PMV response. Finally, chapter 7 revealed that exercise-derived MVs supported endothelial proliferation and migration, while displaying pro-angiogenic potential in vitro. In conclusion, results of this thesis provide original information about MV dynamics, by demonstrating that PMV increase systemically in the circulation not only after but during exercise involving a small and large muscle mass. This MV response seems to be modulated by exercise intensity, and is only partially linked to levels of vascular shear stress. Moreover, circulating MVs produced during exercise present stimulatory angiogenic and mitogenic effects upon endothelial cells in vitro, suggesting a novel potential link between vascular adaptation and exercise training.

Considering current levels of overweight and obesity in the population and the associated adverse health consequences, engaging people with chronic exercise programmes is of heightened importance. During chronic structured exercise programmes, some adults experience adaptive compensatory behavioural responses through increased dietary intake and/or decreased free-living physical activity. These responses can negate the benefits of an exercise-induced energy deficit. However, it is unclear whether young people experience similar responses during chronic structured exercise. Therefore, the experimental research presented in this thesis examined the existence and extent of exercise-induced energy compensation in adolescent girls. To achieve this, a total of 92, 12 to 15 year old girls and 26 adults were recruited into six experimental studies. The Medical Research Council guidance for designing complex interventions was used to structure the experimental chapters into development (Chapters 4 to 7), piloting (Chapter 8) and evaluation (Chapter 9). The first experimental study (Chapter 4) demonstrated that typical daily variation of total energy expenditure (TEE) in adolescent girls is ~3% when estimated by the Actiheart. Physical activity energy expenditure (AEE) variation was found to be ~10%. In the second experimental study (Chapter 5) the agreement and variability of laboratory buffet meals test days was investigated. The results demonstrated typical daily variation of 8.7% in laboratory-based energy intake (EI) in adolescent girls aged 12 to 15 years. Furthermore, a buffet meals familiarisation day is recommended to reduce the variability in EI. Estimation of EI was further explored in Chapter 6 using a digital photography method. This study demonstrated potential for EI assessment using digital photography, but highlighted that, at present, a supplementary written record of EI is required to overcome the limitations associated with missing photographs. Chapter 7 explored themes related to recruitment and retention of adolescent girls to chronic exercise intervention studies. The seven recommendations identified were used to recruit and retain participants in a twelve week pilot exercise intervention study with adolescent girls (Chapter 8). There was no evidence of energy compensation behaviours on a group level; however, high individual variability in both EI and EE behaviours was apparent. The final experimental chapter (Chapter 9) evaluated the fidelity of the exercise intervention and compliance with the measurement of primary outcome variables. Intervention fidelity was largely upheld. On average, participants attended 94% of exercise sessions and 73% of the participants met their individual target heart rate zone. Focus groups with the participants and parents highlighted preference for school-based exercise sessions due to increased variety and convenience, and recommendations for future estimation of free-living EI and EE. Collectively, these studies suggest there is value in pursuing the investigation of energy compensation behaviours in adolescent girls using a mixed methods approach. These studies demonstrate the factors requiring attention when designing and delivering complex interventions to investigate exercise-induced energy compensation in adolescent girls. In particular, methods for estimating free-living EI and EE require further attention before attempting to conduct such research in a larger sample.

Change of direction speed (CODS) is an important determinant of performance in many sports. Greater stiffness of the lower limb should be beneficial to CODS, but this had not been well investigated. The purpose of this thesis was to establish the relationship between vertical stiffness, vertical stiffness asymmetries and CODS, with a view to augmenting CODS performance. The pilot study and studies 1-2 sought to determine the most reliable and ecologically valid method to assess stiffness in athletes required to perform changes of direction. The pilot study reported that the use of ultrasonography to determine Achilles tendon stiffness did not demonstrate appropriate reliability for inclusion in subsequent studies. Coefficients of variation (CVs) in excess of 27% were reported during an isometric plantar flexion task. Study 1 reported that CVs for vertical stiffness were lower when assessed during unilateral drop jumping (~7%) than during bilateral drop jumping (~12%) or bilateral hopping (~14%). Study 2 reported that the expression of vertical stiffness (P = 0.033) and vertical stiffness symmetry angle (P = 0.006) was significantly different across three performance tasks: unilateral drop jumping, bilateral drop jumping and bilateral hopping. Asymmetry percentages between compliant and stiff limbs were 5.6% (P < 0.001; d: 0.22), 23.3% (P = 0.001; d = 0.86) and 12.4% (P = 0.001; d = 0.39), respectively. Given the findings of studies 1 and 2, this thesis demonstrated the reliability and validity of a novel method by which to assess vertical stiffness - the unilateral drop jump. This task was used in subsequent studies to measure vertical stiffness. Study 3 sought to determine if vertical stiffness and vertical stiffness asymmetries influenced CODS performance determined during a 90o cutting task. Multiple regression analyses reported that mean vertical stiffness and asymmetry in jump height explained 63% (r2 = 0.63; P = 0.001) of CODS performance. Study 3 was the first investigation to demonstrate the importance of vertical stiffness to CODS performance. Study 4 sought to determine if acute exercise interventions designed to augment vertical stiffness would improve CODS. Unilateral and bilateral ‘stiffness’ interventions were evaluated against a control condition. CODS performances following the unilateral intervention were significantly faster than control (1.7%; P= 0.011; d = -1.08), but not significantly faster than the bilateral intervention (1.0% faster; P = 0.14; d = -0.59). Versus control, vertical stiffness was 14% greater (P = 0.049; d = 0.39) following the unilateral intervention. Study 4 demonstrated that a novel unilateral ‘stiffness’ intervention improved vertical stiffness and CODS performance. This highlights that the potential applicability of unilateral stiffness interventions in the pre-performance preparation of athletes.

Background: Studies have reported that preschool children may not be sufficiently active according to guidelines. This is worrying because early childhood is a critical period for the establishment of sedentary behaviour (SB) and physical activity (PA) habits, which have immediate and long term influences on health. The majority of evidence on levels, determinants, and health consequences of SB and PA in young children is, however, based on subjective measures in predominately White children aged three years or older. Aims: To 1) assess the feasibility and acceptability of using three different accelerometers in South Asian and White British 2-3 year olds and their parents; 2) calibrate and validate the accelerometers to measure SB and PA in 2-3 year olds; 3) investigate the influence of 5-, 10-, and 15-second epochs on time spent in SB, light PA, and moderate-to-vigorous PA (MVPA) in 2-3 year olds; and 4) assess the feasibility of measuring the habitual SB and PA with the ActiGraph GT3X+ accelerometer in South Asian and White British 2-3 year olds and their parents. Methods: Focus groups were performed with 17 South Asian and White British mothers and the audio-recordings were transcribed verbatim and analysed with thematic analysis (Aim 1). To calibrate the three accelerometers against direct observation (Aim 2), semi-structured activity sessions were run with 18 South Asian and White British 2-3 year olds. Mixed-effects regression and receiver-operating characteristics (ROC) curve analysis were used to generate prediction equations and 5- and 10-second cut-points to assess children s SB and PA. Validity of the generated cut-points against direct observation (Aim 2) was assessed in a separate sample of 20 White British and Black African 2-3 year olds during free-play, using Cohen s kappa, ROC curve analysis, Bland-Altman plots, and Lin s concordance coefficient. Differences in estimated time spent in SB, light PA and MVPA from 5-, 10- and 15-second epochs were tested with repeated-measures ANOVA and paired t-tests in the calibration sample (Aim 3). A pilot study was conducted with 120 South Asian and White British families from a birth cohort study to address aim 4. Study intake and compliance with an 8-day measurement protocol were calculated, and differences between ethnicities were assessed with the Chi-square test. Results: The ActiGraph GT3X+ was the most widely accepted accelerometer, with the least amount of issues raised by mothers. Practical and software issues with the Actiheart and activPAL3 during the calibration phase resulted in insufficient good quality data collected, which made it unfeasible to calibrate both monitors. The overall 5-second Axis1 cut-points for the ActiGraph GT3X+ provided a valid tool to measure the SB and total PA of 2-3 year olds in free-living conditions. Using 10- and 15-second epochs overestimated children s light PA and underestimated time spent in SB and MVPA. Less South Asian than White British families were recruited into the study, and less South Asian than White British children complied with the 8-day measurement protocol. There were no ethnic differences in the number of children and parents providing enough accelerometry data (i.e. ≥ 3 valid days), or the number of parents complying with the measurement protocol. Conclusions: The results demonstrated that it is feasible to use the ActiGraph GT3X+ to assess the habitual SB and PA of a bi-ethnic sample of 2-3 year old children and their parents. The accurate assessment of SB and PA in 2-3 year olds using the overall 5-second Axis1 cut-points developed and validated in this thesis will enable researchers to investigate the levels, determinants, and health consequences of SB and PA. Such research will inform public health policies and interventions to improve children s health.

Static and dynamic balance are essential in daily and sports life. Many factors have been identified as influencing static balance control, two of which are carrying additional weight and localized muscle fatigue but their influence on dynamic balance in sport activities has not been fully established. Therefore, the aim of this thesis was to investigate the characteristics of dynamic balance in sport related activities, with specific reference to the influence of body mass changes and muscular fatigue. Study one: The objectives of study one (methodological study, n = 5) were to apply the extrapolated Centre of Mass (XCoM) method and other relevant variables (centre of pressure, CoP; Centre of Mass, CoM; shear forces, Fh; kinetic energy, KE; momentum, P; and angular impulse, AI) to investigate sport related activities such as hopping and jumping. Many studies have represented the CoP data without mentioning its accuracy so several experiments were done to establish the agreement between the CoP and the projected CoM in a static condition. It was found that there was an inaccuracy with the average difference about 4mm. This meant that the angular impulse could not be reliably calculated. Its horizontal component, representing the Friction Torque (Q), could be reliably computed for dynamic balance. The implementation of the XCoM method was found to be practical for evaluating both static and dynamic balance. The general findings were that the CoP, the CoM, the XCoM, Fh, and Qwere more informative than the other variables (e.g. KE, P, and AI) during static and dynamic balance. The XCoM method was found to be applicable to dynamic balance as well as static balance. Study 2: The objectives of study two (baseline study, n =20) were to implement Matlab procedures for quantifying selected static and dynamic balance variables, establish baseline data of selected variables which characterize static and dynamic balance activities in a population of healthy young adult males, and to examine any trial effects on these variables. The results indicated that the implementation of Matlab procedures for quantifying selected static and dynamic balance variables was practical and enabled baseline data to be established for selected variables. There was no significant trial effect. Recommendations were made for suitable tests to be used in later studies. Specifically it was found that one foot-tiptoes tests either in static or dynamic balance are too challenging for most participants in normal circumstances. A one foot-flat eyes open test was considered to be representative and challenging for static balance, while adding further vertical jump and landing tests (two feet flat and one foot flat vertical jump) to the horizontal jumping and hopping for dynamic balance was considered to be more representative of sports situations. The main differences between horizontal and vertical jumping were in anterior-posterior direction. Study 3: The objectives of study three (differentiation study, n =20) were to establish the influence of physical (external added weight) and neurophysiological (fatigue) factors on static and dynamic balance in sport related activities. This was typified statically by the Romberg test (one foot flat, eyes open) and dynamically by jumping and hopping in both horizontal and vertical directions. Statically, added weight increased body's inertia and therefore decreased body sway in anterior-posterior direction though not significantly. Dynamically, added weight significantly increased body sway in both mideo-lateral and anterior-posterior directions, indicating instability, and the use of the counter rotating segments mechanism to maintain balance was demonstrated. Fatigue on the other hand significantly increased body sway during static balance as a neurophysiological adaptation primarily to the inverted pendulum mechanism. Dynamically, fatigue significantly increased body sway in both mideo-lateral and anterior-posterior directions again indicating instability but with a greater use of counter rotating segments mechanism. Differential adaptations for each of the two balance mechanisms (inverted pendulum and counter rotating segments) were found between one foot flat and two feet flat dynamic conditions, as participants relied more heavily on the first in the one foot flat conditions and relied more on the second in the two feet flat conditions. Conclusion: Results from this thesis are expected to aid towards advancing the understanding of balance in sport related activities, and can provide a solid foundation for future work in this area. In particular, a method was established to assess static and dynamic balance, baseline data for these associations was provided, and differential adaptations to physical or neurophysiological constraints were found. Valuable associations between specific variables and the first two mechanisms of balance were demonstrated.

The World Health Organisation ([WHO], 2007) declared obesity as the public health threat of the 21st century. Currently, the Maltese adult population ranks as the heaviest in the Euro‐Mediterranean region. In response to a gap in Maltese research on the area of obesity and food consumption, this PhD aimed to gather local data to unearth behavioural‐psychological factors that could be implemented in local interventions. The focus of the PhD was narrowed to women with families based on literature that has identified motherhood as a salient point of transition that amplifies the weight trajectories for adult women. A mixed‐methods approach guided the methodology of the PhD programme with four studies carried out sequentially in two phases. The findings of the qualitative phase revealed that weight management for Maltese mothers was enmeshed with gender norm expectations surrounding motherhood. For mothers with a higher BMI, their relationship to food was a significant barrier to weight loss maintenance. Mothers with a lower BMI or who maintained their weight pointed at their food planning ability to manage their diet. The quantitative phase extended literature on the dimensional validity of the Dutch Eating Behaviour Questionnaire (DEBQ) (Van Strien et al., 1986) by reproducing its factor structure and ascertaining its reliability among Maltese women. This was the first validation of an eating behaviours assessment tool in Maltese and the first validation of the DEBQ in a Semitic language. Finally, Structured Equation Modelling revealed how food planning could act as a mediator to restrained and external eating styles to increase fruit and vegetable snacking and decrease high calorie snacking. In addition to the implications to theory, it is believed that these findings have worthy practical implications through tailored eating behaviour interventions, by targeting food planning to counterbalance the impact of external eating among Maltese mothers.

It has been established that Wingate-based high-intensity training (HIT) consisting of 4 to 6 x 30-s all-out sprints interspersed with 4-min recovery is an effective training paradigm. Despite the increased utilisation of Wingate-based HIT to bring about training adaptations, the majority of previous studies have been conducted over a relatively short timeframe (2 to 6 weeks). However, activity during recovery period, intervention duration or sprint length have been overlooked. In study 1, the dose response of recovery intensity on performance during typical Wingate-based HIT (4 x 30-s cycle all-out sprints separated by 4-min recovery) was examined and active recovery (cycling at 20 to 40% of V̇O2peak) has been shown to improve sprint performance with successive sprints by 6 to 12% compared to passive recovery (remained still), while increasing aerobic contribution to sprint performance by ~15%. In the following study, 5 to 7% greater endurance performance adaptations were achieved with active recovery (40%V̇O2peak) following 2 weeks of Wingate-based HIT. In the final study, shorter sprint protocol (4 to 6 x 15-s sprints interspersed with 2 min of recovery) has been shown to be as effective as typical 30-s Wingate-based HIT in improving cardiorespiratory function and endurance performance over 9 weeks with the improvements in V̇O2peak being completed within 3 weeks, whereas exercise capacity (time to exhaustion) being increased throughout 9 weeks. In conclusion, the studies demonstrate that active recovery at 40% V̇O2peak significantly enhances endurance adaptations to HIT. Further, the duration of the sprint does not seem to be a driving factor in the magnitude of change with 15 sec sprints providing similar adaptations to 30 sec sprints. Taken together, this suggests that the arrangement of recovery mode should be considered to ensure maximal adaptation to HIT, and the practicality of the training would be enhanced via the reduction in sprint duration without diminishing overall training adaptations.

Le but cette thèse était d’explorer l’influence du niveau d’activité physique et du niveau de performance physique sur la densité minérale osseuse, la géométrie osseuse de la hanche et le score de l’os trabéculaire chez de jeunes hommes en surpoids et obèses. Trois principales études ont été menées. Une première étude a montré que la pratique d’activités physiques a un effet positif sur le CMO, la DMO et la section transversale du col fémoral chez les hommes en surcharge pondérale. Une deuxième étude a suggéré que le niveau d’activité physique influence positivement les paramètres osseux chez les hommes en surpoids et obèses et que l’optimisation de la masse maigre, de la VO2 max (L/min) et de la force maximale des membres inférieurs peut aider à prévenir l’ostéoporose chez les hommes en surpoids et obèses. Enfin, une dernière étude, a été la première à démontrer une relation positive entre la VO2 max (ml/mn/kg) et les indices de résistance osseuse du col fémoral (le CSI, le BSI et l’ISI) chez les jeunes hommes en surpoids et obèses et a donc suggéré que l’augmentation de la VO2 max chez les hommes en surpoids et obèses pourrait aider à réduire les fractures stéoporotiques. Ces différents résultats suggèrent une adaptation ostéogénique significative des jeunes hommes en surpoids et obèses en réponse à l’entrainement physique. / The aim of this thesis was to explore the influence of physical activity level and physical performance on bone mineral density, hip geometry and trabecular bone score in young overweight and obese men. Three main studies have been conducted. The first study has shown that physical activity practice has a positive effect on BMC, BMD and femoral neck crosssectional area in overweight men. The second study has shown that physical activity level positively affects bone variables in overweight/obese men and that increasing lean mass, VO2 max (L/min) and muscular strength of the lower limbs can help to prevent osteoporosis in overweight and obese men. Finally, the last study, was the first to show positive associations between maximal oxygen consumption (milliliter per minute per kilogram) and composite indices of FN strength (CSI, BSI and ISI) in young overweight and obese men and therefore suggested that enhancing VO2 max in overweight and obese men may help to reduce osteoporotic fractures. These different results suggest a significant osteogenic adaptation in young overweight and obese men in response to physical training.

Le cancer de la prostate est un problème de santé publique majeur. L’exercice physique régulier fait désormais partie des moyens bien décrits pour améliorer la qualité de vie des patients atteints de cancer. Une activité physique quotidienne est donc recommandée pendant et après le traitement. Toutefois, aucune étude ne s’est intéressée aux interactions potentielles entre l’exercice physique, la consommation d’antioxydants et la radiothérapie. L’absence de connaissances sur les mécanismes moléculaires associés à ces stratégies connues pour moduler le stress oxydant, un facteur crucial dans l’évolution de la carcinogenèse prostatique, soulève aujourd’hui une question majeure : l’exercice physique influence-t-il la progression tumorale ? Les objectifs de ce travail de thèse étaient de déterminer les effets de l’exercice physique, combinée ou non à d’autres stratégies, sur la progression du cancer de la prostate et d’identifier des mécanismes moléculaires notamment redox-sensibles impliqués dans ces effets. En s’appuyant sur différentes études in vitro et in vivo, nos travaux ont mis en évidence que l’exercice physique prévient la progression du cancer de la prostate via la régulation du statut redox et de voies de signalisation redox-dépendantes, ou via une modulation de la cholestérolémie ou encore du profil d’expression des miRNAs. Nos travaux démontrent également que l’exercice physique associé à la prise d’antioxydants alimentaires inhibe les effets antiprolifératifs de ces stratégies isolées, et inversement, que l’exercice physique potentialise l’efficacité de la radiothérapie. / Prostate cancer is a major public health problem. It has now been widely recognized that regular physical exercise improves the quality of life of cancer patients. Thirty minutes of physical activity a day is recommended during and after treatment. However, potential interactions of physical exercise, dietary antioxidant intake and radiotherapy have not yet been studied. The lack of knowledge on molecular mechanisms associated with these strategies known to modulate oxidative stress, a key factor in prostate cancer evolution, raises a question: does physical exercise influence the efficiency of patient management and tumor evolution? The objectives of this work was to determine the effects of physical exercise, combined or not with others strategies, on prostate cancer progression and to identify redox sensitive-molecular mechanisms involved in these effects. We used different in vitro and in vivo approaches to achieve these aims. Our researches underline the essential role of physical exercise in prevention of prostate tumor progression, through a redox state and signaling pathways regulation, but also through a modulation of cholesterol levels or miRNA expression profiles. We also demonstrate that physical exercise associated to dietary antioxidant consumption limits anti-proliferative effects of these isolated treatments. Inversely, we reported that regular physical exercise enhances radiotherapy efficiency

This thesis examines intergenerational change in prevalence of and attitudes to physical activity by comparing first and second-generation South Asians in Britain. British South Asians have poorer health outcomes including a higher prevalence of cardiovascular disease (CVD) and diabetes than White British people. Physical inactivity is one of the risk factors for CVD and diabetes. Physical activity levels are lower among British South Asians than the White British population, for reasons that include cultural factors related to being South Asian, the low socioeconomic status of some South Asian groups, and living in deprived neighbourhoods. However, existing literature on physical activity levels does not clearly distinguish between first and second-generations. Understanding generational differences in the influences on physical activity among South Asians is important for developing appropriate interventions. First, I review the existing quantitative and qualitative literature on physical activity in second-generation South Asians. There is some evidence that second-generation South Asians are more physically active than the first-generation. Despite this, second-generation South Asians remain less active than White British people. Neither the quantitative nor the qualitative literature has adequately explored the reasons for these findings. I then use data from the Health Survey for England to explore the ways that adult Indians, Pakistanis and Bangladeshis are physically active. When analysed by age and sex, all South Asians and the White British group were physically active in different ways to each other. However, there was little difference between younger Indians and younger White British people in the contribution of walking to total activity. Finally, I present a qualitative analysis of how ethnicity influences physical activity in second-generation South Asians. I interviewed 28 Indian women living in Manchester, England. I found that a British schooling and messages from the media had strongly influenced second-generation Indian women's attitudes to physical activity. Consequently, their motivations and barriers to physical activity were generally very similar to those reported for White British women. Second-generation Indian women had mostly adopted Western gender roles, with Indian gender expectations having a limited impact on their physical activity. In contrast, the traditional roles of Indian women constrained the leisure-time physical activity of the first-generation Indian women. There was no generational difference in how the local neighbourhood influenced physical activity. This thesis demonstrates clear differences in physical activity prevalence and attitudes between first and second-generation South Asian women in the UK. Interventions aimed at improving local environments for physical activity are likely to help all people living in deprived areas, regardless of ethnic background. Changing generic Western social norms around femininity and being physically active may be more important than tailored interventions for second-generation Indian women.