The studies described have been concerned with two previous untried techniques for measuring the response to exercise. The general aim in both studies was to investigate the relations-between age, activity and the response to exercise (physical condition). In the first study (Part A) the response to exercise was measured using a bicycle ergometer pedalled with one leg. The subjects were in hospital for a meniscectomy. The results showed that bedrest as a model of inactivity caused a decline in physical condition. It also showed that the decline was greatest in those who were initially in the best condition. The older subjects deteriorated less and this appeared to be because their initial condition was the poorest. In the second study (Part B) a method for measuring the response to exercise was developed which is suitable for use with elderly and frail subjects who could not be tested using existing methods. The method consists of self-paced walking at several speeds in a free situation, combined with the tape recording of heart rate and footfall. The assessment of physical condition which can be obtained is the heart rate at a standard walking speed. It was found to correlate with a conventional assessment made using a bicycle ergometer in which the heart rate was standardised on oxygen uptake adjusted for body weight. No age differences have been found in physical condition measured in this way but significant differences were found in performance. The older subjects (aged. between 60 and 80 years) of both sexes walked more slowly than the younger subjects (aged about 20 years) and the older men were found to walk with a shorter stride. These differences may also reflect levels of daily activity.

This study examines the effect that supporting a football team and attending their matches can have on the mental health of the supporters. The examination of the interplay between supporting a team and developing and maintaining some of the conditions needed to maintain good mental health is developed along three main themes. Firstly ideas around a sense of belonging, inclusion, group membership and the impact that such issues have on a person's mental health are investigated. Although supporters, in general, are not prioritised in research about sport, literature from sociology, psychology, sports and mental health areas all suggest that the inclusive nature of the supporting experience can impact positively on the supporters involved. Most of the work done in this field, however, has focused on North American sports such as basketball, baseball and ice hockey. This study explored whether the same impact was actually found in the supporters of English lower league association football. Part of this area of the study addressed the importance that ritual behaviour played in the development of a sense of identity and belonging in the group setting. The second area for exploration, specifically linked to mental health, focuses on the importance of developing and sustaining good relationships and the impact this has on a person's mental health. In a time where much is made of the apparent decrease in the amount of time, and, more importantly, the quality of time spent, between family members (especially parents and children) the study looks at the role of supporting a team in the development of parent child relationships and how the football supporting experience offers opportunities for family members to spend time together. The most prominent of these relationships is the relationship between fathers and sons and the study looks at how football supporting may offer opportunities to develop relationships with specific "ring fenced" time together in an activity that both may be involved with throughout a whole lifetime. The final major theme to develop is around the question of catharsis. Although a disputed concept academically, the idea of cathartic externalisation of emotion is a prominent feature in the data collected. Ventilation of emotion through cathartic behaviours is seen as important by fans in terms of their mental health. Many fans described a conscious system of coping wherein the stresses they accumulated from their day to day lives at home, and at work, are "carried" until the match then vented in the safe environment of the stadium. Fans suggest that the live element of the experience heightens the intensity of the experience as opposed to an experience, such as theatre or cinema, where the outcome of an event is predetermined. Participants in this study are all supporters of Mansfield Town FC and self selected for the study in response to an article on the Mansfield Town FC website and to Radio and TV coverage of the project. The study uses a grounded theory method for collecting and analysing data. In a two stage process diaries were used to collect data from fans and these were analysed with the help of the Nvivo software package to identify recurring themes. These themes formed the foundation of the interview schedule used for data collection in the second phase of the process. The interviews were also analysed with the help of Nvivo and the Grounded Theory steps of open coding and axial coding described by Glaser and Strauss (1967) and Strauss and Corbin (1990) were used to develop a core theory. The main findings reflected the themes outlined above of belonging, relationships and catharsis. Analysis of the data suggests that the identification of the fan with the club, and the identity of the club as part of a local community, helps fans feel part of something bigger than themselves and this generates a sense of belonging, security and warmth. Exploration of the role of relationships in supporters' behaviour suggests that most of the fan' early experiences of being taken to a match were with their fathers and were resonant with a feeling of being old enough to enjoy and appreciate the game and of having some clearly defined time with their fathers which was sacrosanct and expected. This was time which was set aside with a definite purpose and involved a shared experience which was guaranteed to generate interaction and conversation between parent and child on a subject about which each could have a view and exchange an idea. The development of lifelong friendships that cut across age, social background and culture also feature in this area of the research. The text discusses the findings and suggests ways in which the experiences described by the fans, and the resulting impact on them, might be used in a mental health context to help promote better mental health. It makes recommendations about the use of football in general, and football clubs specifically, for this purpose. The study concludes that if the behaviours, thoughts and feelings associated with supporting do offer the benefits outlined in the diaries and interviews used for data collection then it may well be that football clubs, from large superclubs like Manchester United to small local clubs like Mansfield Town, can have a part to play in the maintaining of and promotion of mental health within communities.

Silicon is an essential element in human nutrition, with the symptoms of a silicon-deficient diet being abnormal bone development (Carlisle, 1972). Similarly, animals and bone forming osteoblast-like cells in vitro show an increase in bone growth when supplemented with the soluble, bioavailable form of silicon, orthosilicic acid [Si(OH4)] (Carlisle, 1988). Certain bioactive glass compositions can form a strong chemical bond with bone, doing so by dissolving to form a solution that includes orthosilicic acid which re-polymerises to form a hydrated silica gel layer that adsorbs growth factors, supports cell growth and acts a nucleation bed for bone mineral (Hench, 1980). Bioactive glass degradation products alone have also been shown to significantly enhance the activity of osteoblasts in vitro (Xynos et al, 2001). Pure, crystalline silicon is not soluble in water or body fluids, but when electrochemically etched with hydrofluoric acid, nanoscale silicon hydride-lined pores are formed through the material which render it soluble in aqueous solutions, yielding orthosilicic acid (Canham, 1996). Porous silicon has therefore been proposed as a novel orthopaedic biomaterial, acting in a similar way to bioactive glasses. In addition, the long, narrow pores can be filled with pharmaceuticals, creating a dissolvable drug delivery material with release kinetics that are easily controllable by adjusting the pore morphology and drug loading density (Anglin et al, 2008). This research aims to evaluate porous silicon (pSi) as a therapeutic biomaterial for bone tissue engineering applications in the form of a composite with the biodegradable polymer, polycaprolactone (PCL). pSi microparticles were incorporated into a polycaprolactone matrix and the composites characterised in terms of the ability to generate orthosilicic acids under various conditions. It was found that the composites released silicic acids at a rate proportional to the loading proportion of pSi, with 8% composites (20mg pSi in 230mg PCL) eluting ~400 ng.ml-1 Si per day. At this composition, pSi increased the amount of calcium phosphate formed on the composite in a simulated body fluid and this had the morphology and molar ratio of biological apatite (Ca:P ≈ 1.5). The addition of 8% pSi to polymers enhanced the electroconductivity of hydrogels by two orders of magnitude and did not significantly affect mechanical strength. The release profiles of small molecules such as gentamicin and large hydrophobic proteins such as alkaline phosphatase were enhanced by pre-loading sample drugs into pSi rather than directly loading drugs into PCL. Crucially, the molecules retained their activity following release. Other proteins such as bovine serum albumin were adsorbed onto the surface silica gel layer, suggesting a method for localising growth factors onto biomaterial surfaces. Osteoblasts responded well to 8% pSi-PCL composites, producing significantly more collagen and glycosaminoglycans in vitro. Collagen in the extracellular matrix (ECM) was also significantly more highly crosslinked as determined by the pyridinium content of ECM lysates and was more mineralised than the ECM on PCL alone. The breakdown products of pSi also significantly enhanced the osteoblastic phenotype of cells in vitro. This research demonstrates that porous silicon can be added to polymer-based materials to enhance their effectiveness as biomaterials for orthopaedic tissue engineering.

Meal pattern has been identified as a factor influencing the thermic effect of food (TEF) and metabolic status, and therefore health. This thesis investigated the effects of an irregular meal pattern, with a controlled energy intake, in normal-weight (n=11) and obese with insulin resistance (n=9) females over a 14-day period. Measurements were made of the TEF, circulating glucose, insulin, lipids concentration and appetite regulation, using a crossover design. The irregular intervention period led to a significant reduction in the TEF following a test drink consumption in both normal-weight and obese participants. Glucose iAUC responses to the test drink measured over 3h were higher after the irregular compared with the regular intervention with no difference in the insulin response in the normal-weight study. In the obese study, glucose responses were unaffected by the regular and irregular intervention periods, whilst there was a main effect of meal pattern in insulin responses. In the normal-weight study, fasting GLP-1 decreased after both interventions. In contrast, fasting GLP-1 increased after both interventions in the obese study. Furthermore, in the obese study, the regular intervention produced a higher GLP-1 iAUC compared with the irregular intervention, but there were no such effects in the normal-weight study. The normal-weight study showed that fasting PYY was lower after the interventions compared with before. Moreover, iAUC for PYY increased after the interventions compared with before. However, there were no significant differences in fasting and iAUC PYY responses between the two interventions in the obese study. A regular meal pattern appears to be associated with greater TEF, which might result in more favourable energy balance for weight maintenance. Also, it is likely that a regular meal pattern improved insulin sensitivity in healthy normal-weight females. Therefore, a regular meal pattern could be a lifestyle factor that may promote an individual’s health.

Background Exercise has well known health benefits for older people, however, for some older people with compromised health and mobility participating in exercise is challenging. Chair based exercise is a pragmatic and accessible form of exercise that may be offered in this context, however, there is a lack of good quality evidence and a lack of standardisation in delivery. Method This thesis used the Medical Research Council’s framework for the development and evaluation of complex interventions to develop a community delivered chair based exercise intervention – Progressive Assisted Chair Exercise (PACE). Multiple research methods were undertaken to develop a theoretically driven intervention with a clear rationale for how it was anticipated to work. This included an expert consensus development process, a systematic review of randomised controlled trial literature, and identification of literature on the physiological and behaviour change principles of exercise for older people. The PACE intervention was then tested in a pre and post cohort study in an NHS community service to establish the feasibility of the intervention and whether it resulted in the anticipated outcomes. The acceptability of the intervention was explored through focus groups with older people. Results Experts agreed on a set of 46 principles of chair based exercise through a Delphi technique. The systematic review of randomised controlled trials identified a lack of consistent and good quality evidence for the health benefits of existing programmes. Greater focus on the development of programmes that were underpinned by a sound theoretical framework was recommended. Using the findings from the expert consensus, the systematic review and published guidelines on exercise for older people the PACE intervention was developed to include a 12 week multi-component progressive group or home based programme delivered by a healthcare professional with the knowledge and skills of working with older people and targeted at older people who were unable to participate in standing exercise programmes. The pre and post cohort study demonstrated that the programme was feasible to deliver when tailored to account for individual preferences and the fluctuating health needs of older people. The programme was acceptable to older people when targeted appropriately at those unable to participate in standing programmes and when individual preferences and needs were accounted for. The primary criteria for success of clinically meaningful improvements in lower limb muscle strength and progression to supported standing exercise were observed. Conclusions The PACE intervention as a complex intervention was sufficiently developed and modelled to warrant formal evaluation. Further feasibility work is needed to optimise the evaluation method through a feasibility randomised controlled trial. Further development work for care home and acute rehabilitation populations is indicated.

Regenerative therapeutic solutions are required to address the increasing prevalence of bone and cartilage diseases within the population. Limitations of existing treatments, such as bone graft reconstructions or biomaterial implants, suggest that osteochondral tissue constructs with the ability to support differentiation of mesenchymal stem cells into both osteoblast and chondrocyte lineages is desirable. To date, tissue-engineering approaches have focused on developing individual scaffolds for each osteochondral lineage. Constructs are combined once tissues have developed sufficiently. Unfortunately, delimitation often occurs under normal physiological loading and implants fail. The overall aim of this research project was to develop a scaffold made from a single material with the capacity to maintain osteogenic and chondrogenic cells. In this manner, it was intended to overcome issues arising from delamination and the divergent differentiation requirements for each lineage by providing scaffolds with spatially resolved environments, each supportive of one of osteochondral cell lineages. The work reported here describes a novel method to produce porous chitosan scaffolds with large pore regions (300-425 μm) to promote the osteogenic differentiation of mesenchymal stem cells, and smaller pores (180-300 μm) to encourage chondrogenesis. Porogen properties and cross-linker optimisation were fundamental for the production of a bi-layered chitosan scaffolds containing two distinct pore sizes, successfully achieved in the current project. The architecture of the chitosan scaffolds also permitted the development of a culture medium that could activate simultaneous osteogenic and chondrogenic differentiation in mesenchymal stem cells. More specifically, it was determined that 5-day transient serum treatments with fetal calf serum or human serum, allowed bone and cartilage development. Finally, a perfusion bioreactor system was used to confirm the biocompatibility and osteochondral differentiation potential of the bi-layered chitosan scaffolds.

No description available.

This thesis investigated the impact of sodium acetate infusion on muscle fuel metabolism during low and high intensity exercise and demonstrated a decrease in fat oxidation during the former and a decrease in muscle lactate production during the latter. We propose that the rate of fat oxidation decreased during low intensity exercise due to acetate being preferentially metabolised over fat and possibly reduced muscle free carnitine availability. During high intensity exercise, muscle lactate accumulation decreased due to higher acetyl-CoA supply to the TCA cycle. This thesis also investigated the impact of chronic carnitine supplementation on overall glucose disposal and demonstrated a decrease in blood glucose and serum insulin concentrations following an OGTT in the carnitine group post-supplementation compared to baseline, coupled with a decrease in muscle 2-deoxyglucose accumulation in the carnitine group post-supplementation compared to control. We propose that carnitine-induced increased fat oxidation caused a decrease in hepatic fat deposition which in turn resulted in increasing glucose disposal by the liver. We also propose that increased hepatic glucose disposal resulted in reduced hepatic glucose release and hence diminished serum insulin concentrations. The impact of a chronic lifestyle intervention protocol involving either oral supplementation with carnitine (carnitine group) or placebo (control group) combined with carbohydrate and protein, together with regular exercise and a prescribed diet on muscle fuel metabolism and body composition in overweight volunteers was investigated in this thesis. This study demonstrated that increased muscle carnitine content caused an increase in fasting fat oxidation and a decrease in carbohydrate oxidation at rest. The carnitine group did not show any significant difference in body mass and body fat mass losses compared to the control group. Whether increased carnitine content, in combination with caloric restriction and exercise, has any impact on body composition seems likely but needs further investigations.