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The aim of this thesis was to investigate the impacts of physical activity (PA), cardiorespiratory fitness (CRF), body composition and lifestyle education on cardiometabolic (CM) risk in 10-11 year old children. This broad aim was approached using three studies. Studies 1 and 2 were cross sectional observational studies, and study 3 was a clustered randomised control trial, with intervention effects assessed at post intervention and again at 8 to 10 weeks after the intervention. Initially, in the first cross sectional study (Chapter 4) the relationships between non- invasive (LV Mass, E/A, E'/A', E/E', trunk fat mass, whole body fat mass) and invasive CM risk markers (CRP, HOMA-IR, adiponectin, TC: HDL-C), and between all risk markers and CRF (V02 peak), time spent sedentary, moderate to vigorous intensity PA (MVPA) and vigorous PA (VPA) were investigated in 10-11 year old children (n=62). The key findings were significant but generally weak relationships present between some of the non- invasive and invasive markers of CM risk and risk markers also had significant correlations with measures of CRF and PA. CRP was significantly positively correlated with whole body fat in boys (rho = 0.486, p < 0.05) and girls (rho = 0.485 , p < O.Ol) and with trunk fat mass in boys (rho = 0.384, p < 0.05) and girls (rho =0.489, p < O.Ol). Adiponectin was negatively correlated with whole body fat (rho = -0.446, p < 0.05, and R=-0.697, p < O.Ol) and trunk fat mass (rho = -0.614, p < O.Ol; rho = -0.475, p < O.Ol) in boys and girls respectively, and in girls adiponectin also correlated positively with E'/A' (r=0.356, p < 0.05). In boys only, TC:HDL-C was positively correlated with whole body fat (rho =0.407, p < 0.01) and trunk fat mass (rho =0.391, p < 0.05). ; V02Peakwas negatively correlated with CRPin boys (Rho = -0.492, p < 0.05) and HOMA-IR in girls (Rho =-0.522, p < 0.01). V02Peak was also negatively correlated with whole body fat (rho =-0.515, p < 0.01; r=-0.697, p < O.Ol) and trunk fat mass (rho=-0.494, p < 0.05; rho =-0.706, p < 0.01) in boys and girls respectively. Both MVPA and VPA correlated negatively with TC: HDL-C in girls (rho= -0.396, p < 0.05; rho =-0.428, p < 0.05) and MVPA correlated with whole body fat (rho= -0.602, p < O.Ol) and trunk fat mass (rho=-0.65, p < 0.01) in boys. VPA also correlated with whole body fat in girls (rho= - 0.544, p < O.Ol) and with trunk fat mass in both boys (rho= -0.428, p < 0.05) and girls (rho= - 0.468, p < 0.01). Time spent sedentary had a positive correlation with whole body fat in boys (rho = 0.429, p < 0.05). This study demonstrated that risk factors clustered in individuals and that relationships were present between invasive and non-invasive markers of cardiometabolic risk, and provided preliminary evidence to investigate this phenomenon further. The correlations described in this study suggest a clustered risk score which includes both invasive and non-invasive measures may add value to predicting overall risk. The second cross sectional study (Chapter 5) investigated clustered CM risk, by combining invasive markers with non-invasive 'pre-clinical' markers of CM risk into a clustered risk score, in a different cohort of 10 - 11 year old children. Clustered risk scores were negatively correlated with CRFand PA. V02 peakshowed a moderate negative correlation with CRSA (r=-0.57, p < 0.01) and CRS B (r= -0.60, p < O.Ol) VPA showed a moderate negative correlation with CRSA (r= -0.51, p= 0.01) and CRSB (r= -0.50, p=O.Ol). MVPA showed a moderate negative correlation with CRSA (r= -0.44, p= 0.03) and CRSB (r= -0.41, p=0.04). Sedentary time showed a moderate positive correlatcorrelation with CRSA (r= 0.414, p= 0.049). The evidence provided by these two observational studies, Study 1 (Chapter 4) and Study 2 (Chapter 5), along with other literature, as discussed throughout this thesis, gave rationale for an intervention with the aim to reduce negative lifestyle behaviours, of low levels of PA, high levels of sedentary behaviour and poor nutritional balance, increase CRF and maintain a healthy body weight.

This thesis aims to identify physiological and biochemical variables, comparing sex, training status, age and maturity in sub-elite, endurance trained adolescents. Maximal lactate steady state was investigated and the effects of endurance training programmes measured.T he first study assessedth e reliability of absolute running speed, V02, and HR that correspond to the fixed blood lactate reference values of 2.0 and 2.5 mmo1. L"1 and the lactate threshold (LT) and found these measures to be reliable after endurance-trained adolescent runners completed two identical incremental treadmill tests within a 7-10 d period The second study was designed to determine the relationship between physiological variables and endurance running performance in this age group. Track-based, running performance times were available for 18 boys and 14 girls for the 800 m, and 16 boys and 13 girls for the 1500 m. The participants were tested using a step-wise incremental treadmill test and a Wingate anaerobic power test (WAnT) on separate occasions. The results from this study found that for the 1500m, running speeds corresponding to the fixed [BLa ] were a useful measure for assessing performance in endurance trained boys and girls. Unlike previous studies, peak V02 was not a significant physiological predictor of 1500m performance in either boys or girls. For the 1500 m performance in girls the anaerobic measure was no longer significant once variations in size or age had been taken into consideration. Whereas V VO2 peak and running economy may prove to be of some value when considering the 800m for boys, the running speed corresponding to a [BLa ] of 2.5 mmol-L-1 was the only meaningful physiological predictor variable for girls once differences in age and body size had been accounted for. The third study had three main objectives: (1) to identify the exercise intensity that corresponds to the (MLaSS) in adolescent, endurance trained runners, (2) to examine possible between sex differences, and (3) to compare the MLaSS with commonly cited fixed blood lactate reference variables. The participants were first tested using a step-wise incremental treadmill test to establish the blood lactate profile and peak VO 2. The running speed and % peak VO 2 at the MLaSS were not significantly different to those corresponding to the fixed [BL& ] of 2.0 and 2.5 mmol-L-1 (P>0.05). The % HR max at 2.5 mmol-L-1 was also not different to that at the MLaSS, whereas at 2.0 mmol-L-1 it was slightly lower (P<0.05). The running speed, % peak VO 2, and % HR max at the fixed [BLa] of 4.0 mmol-L-1 were significantly higher than those at the MLaSS (P<0.05). In conclusion, it is clear that the MLaSS corresponded to the relatively high exercise intensity in this sample of athletes. It would appear that the running speed, % peak VO 2, and % HR max at the MLaSS lies somewhere between the fixed [BLa ] of 2.0 and 2.5 mmol"L-1. These results confirm earlier work that has suggested a fixed [BLa ] of 2.5 mmol-L-1 may be used with young people' to assess and monitor endurance running performance in place of the more commonly used 4.0 mmol-L-1 that has received so much attention in adult-based studies. The fourth study examined the effect of exercise training on endurance performance, blood lactate profile in relation to running speed (RV) and cardio respiratory function (peak V02) in adolescent runners. This study demonstrated that resting HR, LT and 1 Use of the expression young people is increasingly common since the publication of the text, Young People and Physical Activity by Armstrong and Weisman in 1997. It is used within this document to generically represent the 6 to 18 year age group. 11 RV, HR, V02 and peak V02 at LT were significantly influenced by endurance training. When running time, running velocity and run performance time pre and postintervention were included in the analysis, the intervention did not have a significant effect on peak VO2. When percentage body fat was included as a covariate, there was a positive association with pre and post-training for all groups. The conclusion from these data is that maturity and training both have an effect, especially at supra suggested training levels. The results of the four inter-linked studies support an age-related increase in endurance in aerobic and anaerobic performance and indicated significant differences between boys and girls. From a coaching viewpoint the results reveal that, from the age of 14 to 18 years, runners should be introduced to high intensity training and that changes to the format of middle distance running performance in adolescent competition are recommended.

The aim of the present thesis was to examine imitation of biological motion in adults with autism spectrum disorders. Using a novel behavioural protocol, adults with autism and matched neurotypical control adults imitated models that displayed distinctly different, but biological believable kinematics. In Chapter Two it was observed that adults with autism exhibited low-fidelity imitation of atypical biological motion. In Chapter Three it was observed that when selective-attention instructions were provided, although eye movements recorded during action- observation was similar to controls, imitation of atypical biological motion was still impaired. In Chapter Four across three experiments it was shown that adults with autism exhibit reasonably high-fidelity imitation of atypical biological motion. This was achieved by presenting the to-be-imitated biological models in a fixed presentation structure which is known to facilitate greater integration and consolidation of sensorimotor information. This suggestion was supported by a further study where firstly participants were required to complete a secondary motor task during the inter-trial delay, and when the presentation structure was randomised (similar to Chapters Two and Three) resulting in low-fidelity imitation of atypical biological motion. These findings across the present thesis will be discussed in light of a critical evaluation with respect to current literature on imitation in autism, as well as implications for theoretical accounts of impaired imitation in autism and related sensorimotor control processes. Future considerations and translational research will be discussed, with the intention of offering prospective social rehabilitation protocols in autism.

Cardiovascular disease (CVD) is the leading cause of global mortality, with the incidence of cardiovascular related pathologies remaining a public health burden. CVD encompasses pathologies of the vascular tree and heart, including, for example, peripheral artery disease, coronary heart disease and ischaemic stroke. Atherosclerosis is the primary pathological process leading to CVD and is characterised by a multifactorial pathophysiology that first manifests in the vascular endothelium. Termed endothelial dysfunction, this early marker of atherosclerosis has become a focus of interest for identifying individuals at risk of a profound cardiovascular insult, particularly arising from lifestyle choices such as physical inactivity and calorie-rich diets. Dietary interventions have received increasing attention in recent years as inexpensive strategies to potentially combat the ever-increasing global burden of CVD. A high dietary flavonoid intake is associated with a reduction in CVD risk and several studies have revealed a strong, inverse relation between the regular intake of tea, a major source of dietary flavonoids, and CVD risk. Tea has demonstrated improved conduit artery endothelial function and glucose handling in both healthy individuals and in those with overt CVD. However, the effects of tea on the microvasculature and cerebrovasculature are not yet understood, particularly in relation to lifestyle factors. The primary aim of this thesis was to explore the impact of tea ingestion on peripheral and cerebral micro- and macrovascular function in humans. In an initial methodological study, the day-to-day reproducibility of thermally stimulated cutaneous microvascular function was assessed. Fifteen, healthy males (28 ± 5 yrs, BMI 25 ± 2 kg/m2) attended two experimental trials 2-7 days apart. During each trial, baseline and maximal thermally stimulated forearm skin responses were examined simultaneously at four sites on the dominant forearm using laser Doppler flowmetry (LDF). The following heating protocols were adopted: 1. Rapid 39°C (0.5°C/5-s), 2. Rapid 42°C (0.5°C/5-s) 3. Gradual 42°C (0.5°C/2-min 30-s) and 4. Slow 42°C (0.5°C/5-min). The coefficient of variation (CV) was calculated for absolute flux, cutaneous vascular conductance (CVC; flux/mean arterial pressure, MAP) and CVC expressed as a percentage of maximal CVC at 44°C (%CVCmax) at three different time points; baseline (33°C), plateau (39/42°C) and maximal (44°C). Reproducibility of baseline flux, CVC and %CVCmax was 17-29% across all protocols. During the plateau, Rapid, Gradual and Slow 42°C demonstrated a reproducibility of 13-18% for flux and CVC and 5-11% for %CVCmax. However, Rapid 39°C demonstrated a lower reproducibility for flux, CVC and %CVCmax (21%). Reproducibility at 44°C was 12-15% for flux and CVC across all protocols. The good-to-moderate reproducibility of the Rapid, Gradual and Slow 42°C protocols supported their (simultaneous) use to assess peripheral microvascular function. The aim of Chapter 5 was to examine the acute (2-hour) cutaneous vascular responses to local skin heating following ingestion of black tea in a healthy adult population. Twenty healthy participants (58 ± 5 yrs, BMI 26 ± 4 kg/m2, 9 men) attended two experimental trials (tea, placebo), 7-days apart in a randomised, controlled, double-blind, cross-over design. Participants ingested a single dose of 200 ml black tea or placebo, followed by assessment of forearm cutaneous microvascular function using LDF and three distinct local skin heating protocols to distinguish between axon- and endothelium-dependent vasodilation: 1. Rapid 42°C, 2. Rapid 39°C and 3. Gradual 42°C. On the contralateral arm, full-field laser perfusion imaging (FLPI) was used to assess forearm cutaneous microvascular function during Gradual 42°C. Data were analysed as CVC and %CVCmax. Rapid local heating to 39°C or 42°C demonstrated no effect of tea for flux, CVC or %CVCmax (all P > 0.05). Gradual local heating to 42°C, however, produced a higher skin blood flow following black tea ingestion for absolute CVC (P=0.04) when measured by LDF, and higher absolute flux (P < 0.001) and CVC (P < 0.001) measured with FLPI. No effect of tea was found for %CVCmax when assessed by either LDF or FLPI. The aim of the study outlined in Chapter 6 was to examine the effect of daily green tea consumption (equivalent to 6 cups/day) on changes in peripheral vascular function and glucose handling after a 7-day ‘unhealthy’ lifestyle in healthy males. Twelve healthy males (29 ± 6 yrs, BMI 25 ± 2 kg/m2) underwent two periods of 7-days ‘unhealthy’ lifestyle (UL) comprising of combined physical activity reduction (-50% steps per day) and high fat, high carbohydrate overfeeding (+50% kcal per day, comprising 65% fat) in a randomised, controlled, double-blind, cross-over design. Each intervention period was separated by a 2-week washout. During each 7-day UL-period, participants ingested three doses of an active green tea drink (UL-Tea) or a placebo drink (UL-Placebo) per day at regular intervals. Participants attended the laboratory before and after each 7-day intervention (a total of 4 visits). During each visit the following were examined: mean arterial blood pressure (MAP), dominant forearm cutaneous microvascular function using LDF and local heating protocols 1. Rapid 42°C, 2. Rapid 39°C and 3. Gradual 42°C, macrovascular function using brachial artery and femoral artery endothelium-dependent function via flow-mediated dilation (FMD), carotid artery vasoreactivity to the cold pressor test (CAR%), cerebrovascular function via CO2 reactivity and dynamic cerebral autoregulation, and insulin sensitivity and glucose handling through a mixed-meal (1200kcal, comprising 60% carbohydrates, 33% fat and 7% protein) tolerance test. Linear mixed models (main effects of intervention and time) were used to examine the impact of the lifestyle intervention (pre vs post) and green tea ingestion (UL-Tea vs UL-Placebo). Body mass demonstrated a slight increase following both UL-Tea and UL-Placebo (P > 0.05). MAP was increased after UL-Placebo, whereas it was reduced after UL-Tea (P=0.06). LDF responses to rapid local heating demonstrated non-significant reductions in CVC following UL-Placebo but no difference following UL-Tea (P > 0.05), with a significant interaction of time*condition*temperature observed following Gradual 42°C (P=0.02). Brachial artery FMD was not different pre vs post or between UL-Placebo and UL-Tea (P > 0.05), whereas femoral artery FMD decreased after UL-Placebo, which was prevented during UL-Tea (P < 0.001). CAR% decreased following UL-Placebo, which was prevented during UL-Tea (P=0.04). CO2 reactivity and dynamic cerebral autoregulation demonstrated no differences between UL-Placebo and UL-Tea or over time. Postprandial glucose was increased after UL-Placebo, whereas a reduction in postprandial glucose occurred after UL-Tea (P=0.03). Postprandial insulin levels were higher after UL-Placebo, consistent with insulin resistance, whereas following UL-Tea the insulin response was reduced and demonstrated an interaction of time*condition (P < 0.001). The aim of Chapter 7 was to examine the effect of acute oral (-)-epicatechin ingestion on cerebrovascular function in healthy adults. Seven healthy males (32 ± 13 yrs, BMI 25 ± 1 kg/m2) attended two experimental trials ((-)-epicatechin and placebo) 7-days apart in a randomised, controlled, double-blind, cross-over design. Participants underwent baseline assessment of cerebrovascular function using transcranial Doppler ultrasound (TCD), comprising CO2 reactivity to hypercapnia and dynamic cerebral autoregulation via squat-stand manoeuvres at 0.10 Hz and 0.05 Hz. / Following completion of the baseline measures, participants immediately consumed an oral dose of the test product (2 x 50 mg capsules of (-)-epicatechin or 2 capsules of colour-matched placebo) together with a glass of water, following which participants relaxed in the laboratory. 2-hours post-ingestion repeat measures of cerebrovascular function were performed. Linear mixed models (main effects of condition and time) examined the differences between (-)-epicatechin and placebo interventions (pre vs post) on cerebrovascular function. No differences were observed at pre vs post baseline for middle cerebral artery velocity (MCAv) or MAP (all P > 0.05). There were no differences in the cerebrovascular responses to CO2 or dynamic autoregulation between (-)-epicatechin and placebo. The findings from this thesis suggest that, firstly, use of simultaneous skin local heating protocols provides a valuable means of interrogating the cutaneous microvessels for mechanistic insight in intervention studies. Secondly, current findings evidence improved cutaneous microvascular function following acute black tea consumption. Furthermore, the research work undertaken in this thesis provides important insight into the effects of tea consumption on peripheral (micro- and macro-) vascular function and insulin sensitivity, particularly its abrogative effects on lifestyle-induced vascular impairments. However, the effects of tea consumption on the cerebrovasculature remain uncertain. Overall, based on the current findings, tea consumption presents a simple, inexpensive, non-pharmacological cardioprotective strategy to help combat the ever-increasing global burden of CVD.

Despite growing interest into the role of physiotherapists in providing psychological rehabilitation to athletes during sport injury, very little research exists outside North America, Australia, and New Zealand (e.g., Hemmings & Povey, 2002). Thus, the main purpose of this research was to explore the role of UK chartered physiotherapists in the process of psychological rehabilitation from sport injuries. This thesis consists of four studies. With the intention to gain further insights into the physiotherapists’ views on the psychological aspects of their work, study one used the Physiotherapists and Sport Psychology Questionnaire (PSPQ; Hemmings & Povey, 2002) in a national survey with 361 UK chartered physiotherapists working in sport medicine. The results from the survey provided useful insights into the ways in which psychological interventions are currently employed in rehabilitation physiotherapy. In study two, these findings were explored further, by developing a questionnaire survey to explore chartered physiotherapists’ (N = 22) preferred method of sport psychology intervention training. With the purpose of gaining an insight into the physiotherapists’ personal experiences in using psychological interventions with injured athletes, study three adopted a qualitative approach, in which semi-structured interviews were conducted with seven UK chartered physiotherapists. The findings from the Interpretative Phenomenological Analysis (IPA; Smith, 1996) provided deeper understanding on physiotherapists current knowledge on, and their past experiences and opinions on using range of psychological interventions in their work with injured athletes. Similarly study four used semi-structured interviews and IPA with ten athletes who had previously encountered moderate or severe sport injuries requiring physiotherapy treatment. The findings revealed useful information on the physiotherapists’ role in providing psychological support and using psychological interventions in their work with injured athletes. In conclusion, the research presented in this thesis makes a contribution to knowledge by: (a) providing an insight into the views of chartered physiotherapists in the UK on psychological content of their practice, (b) making preliminary suggestions into how further training in sport psychology for chartered physiotherapists could be delivered, (c) enabling deeper understanding of physiotherapists current practices and past experiences in utilising selected psychological interventions in their work, and (d) giving a voice to injured athletes with regard to the role of physiotherapists in providing psychological support during sport injury rehabilitation.

The rising tide of obesity and type 2 diabetes has been recognised to have reached epidemic proportions. There is a significant burden of mortality and morbidity associated with the development of these conditions and current estimates suggest that the burden of disease in the next two decades is likely to place considerable strain upon healthcare systems, particularly in the developing world. The development of insulin resistance is a key contributor to the pathogenesis of type 2 diabetes, however the origin of insulin resistance is complex and it is currently unclear precisely how the inter-related components of this metabolic dysfunction are triggered. Obesity is also implicated in the pathogenesis of insulin resistance and represents a risk factor which is potentially modifiable by lifestyle interventions such as exercise and weight loss. Observational and prospective studies have also shown the benefits of lifestyle intervention in reducing the incidence of diabetes in those judged to be at greater risk. People with a parental history of type 2 diabetes have an increased lifetime risk of diabetes and frequently display metabolic abnormalities which, despite persisting normoglycaemia, are evidence of a ‘pre-diabetic’ state and which may themselves carry increased morbidity and mortality. Observational studies suggest a greater difference in insulin sensitivity between active and sedentary offspring, compared to the difference between active and sedentary individuals with no diabetes family history. This is thought to represent an interaction between positive energy balance, a sedentary lifestyle and a ‘thrifty genotype’. These observations suggest that individuals with a parental history of diabetes are more susceptible to the deleterious health effects of a sedentary lifestyle, but that they may be more responsive to an increase in physical activity. Exercise interventions can be expected to have positive effects upon metabolic health and adiposity however, the individual response to exercise is extremely variable. Other factors such as lifestyle alteration have been implicated in the difference between the observed and predicted response to exercise. Therefore, the aim of this thesis was to examine the physical, metabolic and lifestyle differences between sedentary pre-menopausal women with a parent with type 2 diabetes and matched control subjects with no family history of the condition. In particular, this thesis aimed to explore the effect of an aerobic exercise intervention on metabolic health and body composition, whether the response to exercise is dependent upon a familial history of diabetes and the processes by which exercise might induce any observed changes. In order to explore the impact of a sedentary lifestyle on women with, and without a family history of type 2 diabetes, thirty four pre-menopausal, sedentary women with a parental history of diabetes (Offspring) and thirty six matched women without a familial history of diabetes (Controls) were recruited. Assessments of body composition, insulin sensitivity, adipose tissue-derived hormone concentration, substrate utilisation, endothelial function by carotid-radial pulse wave velocity, cardiorespiratory fitness, diet and habitual physical activity were performed. Twenty eight Offspring subjects and thirty four matched Controls participated in a seven-week aerobic exercise intervention, training at 65-80 % of predicted maximal heart rate with incremental increases in training duration on a weekly basis. The previously described assessments were performed before and 15-24 hours after the intervention and in a subgroup of 19 Controls and 17 Offspring subjects, further assessments of insulin sensitivity, adipose tissue-derived hormone concentration, substrate utilisation and endothelial function were performed after a further three day period without exercise. In order to determine potential mediators of exercise-induced fat loss fifty five women participated in measurements of substrate utilisation, body composition, endothelial function, insulin sensitivity, cardiorespiratory fitness, dietary intake and habitual physical activity prior to, and after the seven week exercise intervention. The findings from these studies confirmed that sedentary women with a family history of type 2 diabetes displayed lower insulin sensitivity than those without a parental history of diabetes. In addition, insulin resistance in this group appears to be related to a greater sensitivity to the influence of adipose tissue, particularly circulating non-esterified fatty acids and adipose tissue-derived inflammatory cytokines. In Offspring alone, baseline insulin sensitivity was associated with plasma adiponectin concentration and negatively associated with circulating non-esterified fatty acid concentration. These associations may represent physiological attempts to compensate for developing insulin resistance. Offspring also displayed an augmented metabolic response to the exercise intervention in comparison to Controls. This study showed a 23% increase in post-intervention insulin sensitivity in Offspring with no significant increase in insulin sensitivity in Controls despite a similar improvement in cardiorespiratory fitness and adherence to the exercise regime. Improved post-intervention insulin sensitivity was accompanied by reduced circulating leptin, increased fat and decreased carbohydrate oxidation in both fasting and post-glucose states. No change in diet was observed but Offspring appeared to increase their level of habitual physical activity. The magnitude of change in insulin sensitivity was associated with a parental history of diabetes, but stronger associations were observed between baseline insulin resistance and an ability to reduce circulating leptin in response to exercise. Wide individual variation in fat mass change was observed in the response to exercise, and as expected the strongest predictor of exercise-mediated fat mass reduction was the net energy cost of the intervention. However, a change in fasting respiratory exchange ratio (RER), suggesting an increase in fat oxidation was also independently associated with reduced fat mass. The combined findings of this thesis suggest that sedentary pre-menopausal daughters of people with type 2 diabetes are more insulin resistant and that this state is, in part, a consequence of heightened sensitivity to fatty acid and inflammatory cytokine release from adipose tissue. However, it would also appear that they represent a high-risk group who are susceptible to the insulin-sensitising effects of exercise and that this may be mediated by a metabolic pathway which involves reductions in circulating leptin concentrations. Finally, the ability to lose fat mass in response to exercise is related to the energy deficit incurred by the activity but also by an individual’s ability to shift fasting substrate utilisation towards fat oxidation. Public health strategies have traditionally focused upon lifestyle interventions which are directed at the population in general. However, awareness of the risks conferred by obesity and familial history of type 2 diabetes and the potential benefits of intervention may suggest that targeting public health resources towards these high-risk groups is a more appropriate and effective strategy.

Point-of-choice prompts consistently increase stair climbing in public access settings. Comparison of message content, however, is rare. Chapter two reports that, after controlling for the effects of traffic, similar effects on stair climbing were evident for a more specific and a simpler heart-health message. Chapters three to five demonstrate that specific, calorific expenditure messages were associated with significantly increased stair climbing in public access and workplace settings, with greater increases in overweight than normal weight individuals (chapter four). Chapter three investigated the single and combined effects of volitional and motivational intervention components, in a tram station, to test the theory underpinning the success of point-of-choice prompts. Both components positioned simultaneously were required to increase stair climbing where choosing the stairs resulted in a time delay for pedestrians due to the site layout. Similarly, a motivational intervention alone did not increase stair climbing in the workplace (chapter five). When supplemented with a volitional, point-of-choice prompt at the time the choice of ascent method is made, a significant increase in stair climbing occurred. Analysis should adjust for potential moderating effects of pedestrian traffic, time of day, demographics and building characteristics; failure to do so may mask the true impact of the intervention.

Early detection of biomarkers of tumour treatment response improves clinical management, in vivo. Magnetic resonance spectroscopy (MRS) has demonstrated potential for identifying early biomarkers of effective treatment. However, more detailed in vitro studies are required to improve our understanding and facilitate its use. The aim of this study is to determine ¹H high-resolution magic angle spinning (HR-MAS) nuclear magnetic resonance (NMR) biomarkers of cytostasis and cell death in a rat glioma BT4C cell line. Cytostasis and cell death were induced in BT4C cells using cisplatin and substrate free medium, respectively. Cell viability was examined by various techniques. The lipid and metabolite alterations in whole cells were investigated by ¹H HR-MAS NMR. Significant alterations in lipids and metabolites were detected in response to cytostasis or necrosis. NMR lipid accumulation was associated with an increase in cytoplasmic lipid droplets seen prior to morphological and molecular markers of cell death. Significant differences were detected in individual choline containing metabolites (CCMs), emphasising the importance of identifying CCMs separately. Alterations were also detected in lactate, alanine, glycine, glutamate, and succinate levels, suggesting changes in the energy metabolism pathways which may provide novel biomarkers in vivo. ¹H HR-MAS NMR reveals alterations in lipids and metabolites during cytostasis and cell death which may provide early markers of treatment efficacy.

Tendon and ligament damage causes extreme pain and decreased joint functionality. Current repair methods cannot restore original joint biomechanics nor promote regeneration of native tissue. Recent advances in tendon and ligament repair have involved engineering tissue using cell-seeded scaffolds. Self-aligned cellular structures, similar to those in ligaments and tendons, have been successfully formed, albeit with weak attachment between construct and bone. Calcium phosphates form an intimate bond with both soft and hard tissues and have successfully been used in tissue engineering bone, whilst hydrogels have often been used as cellular scaffolds. This thesis explores agarose, gelatin, carrageenan and fibrin hydrogels as potential soft tissue scaffolds. Fibrin gel exhibited high cellular compatibility with highest metabolic activity on day 14. Although the cellular gel contracted significantly, it was found that the dry weight remained stable in both the acellular and cellular forms. 3D powder printed calcium phosphate scaffolds remained structurally stable after immersion in cell culture media with immersion in protein-rich sera promoting tenocyte attachment. Bracket designs were developed to enhance grip of the cell-seeded fibrin. Ligament constructs were selfsupporting and exhibited structural characteristics similar to native connective tissue. Tenocyte density peaked on day 14, with added L-proline and ascorbic acid inducing a constant level of glycosaminoglycans and 7.4 ± 1.5 % w/w collagen. This research may significantly enhance the clinical application of tissue engineered ligaments and tendons.