Probiotics are generally live preparations of bacteria that exert beneficial effects on host health when ingested in sufficient quantities. The novel probiotic Escherichia coli strain Nissle 1917 (EcN) has been shown to have a number of beneficial effects in this context, including protection against food-borne pathogens and infectious diarrheal diseases, and maintaining remission of inflammatory bowel diseases by virtue of its anti-inflammatory properties. However, little is known regarding the mechanisms underlying the beneficial effects of this organism. The overall aim of this work was to provide a greater understanding of the mechanisms through which EcN interacts with the mammalian gastro-intestinal epithelium to benefit human health.

Drug eluting beads (DEB) are employed in the treatment of solid hypervascularised malignant tumours by a method called trans-arterial chemoembolisation (TACE). When the microcirculation to a tumour is blocked, oxygen levels decrease to critically low levels causing the tumour to become hypoxic. Hypoxic tumours are known to be chemoresistant and send out growth factor signals leading to angiogenesis and metastasis of tumour cells to other parts of the body. Commercially available DEB are unable to respond to the conditions of hypoxia and will continue to release drug at a constant rate via ionic exchange through the hydrogel. It is therefore recognised that an avenue for improvement would be the development of novel bioresponsive DEB that are able to react to the conditions of hypoxia to overcome chemoresistance associated with the tumour cells.

The introduction of highly active antiretroviral therapy (HAART) has dramatically improved the life expectancy of HIV infected individuals. With the increased lifespan, complications associated with HAART are becoming more evident. Together with HIV itself and a higher prevalence of traditional risk factors, the antiretroviral agents are linked to an increase in cardiovascular diseases in the HIV population. In the present in vitro study the direct cardiac effects of a nucleoside reverse transcriptase inhibitor (NRTI) abacavir in combination with palmitic acid or cobalt chloride mimicking a diet high in saturated fatty acids or hypoxia respectively, were studied. Exposure to abacavir has been associated with an increased risk of myocardial infarction in clinical studies, but the damaging molecular mechanism remains elusive. Furthermore the in vitro cardiovascular effects of three non-nucleoside reverse transcriptase inhibitors (NNRTIs) were investigated; first generation NNRTI efavirenz and the second generation NNRTIs rilpivirine and etravirine.

Haemophilia is an inherited condition in which circulating blood clotting factors are much reduced or absent resulting in the tendency to bleed into joint cavities where the ankle is the most commonly affected. Prophylactic replacement of clotting factors has much improved joint health in the majority of people with haemophilia however many continue to develop joint disease. Purpose. To explore the potential for non-haematological factors to influence the development of haemophilic arthropathy at the ankle. Methods. This study had two phases. Factors for investigation were determined using a Delphi process and subsequently preliminary clinical instrument testing occurred. Finally a case-control correlational study was carried out to investigate the presence of selected factors in a haemophilia cohort compared with normal volunteers. Results. Forty-two factors reached consensus from the Delphi Process of which 22 were selected for onward investigation comprising musculoskeletal, exercise, and haematological factors. In a case-control study with 90 participants, six factors successfully differentiated the Haemophilia Ankle group from the others. A further three factors separated people with haemophilia from normal volunteers representing musculoskeletal differences that cannot be attributed to arthropathy. A regression model was developed comprising: the Ankle Lunge Test, Foot and Ankle Ability Measure (FAAM), Duration of Exposure to a key sport and Subtalar joint inversion which correctly predicted 89.7% of cases with 86.7% sensitivity and 92.9% specificity. Conclusions. These results represent the first attempt to understand the interaction of factors that influence the arthropathy development. The FAAM sports subscale and Duration of Exposure to a key sport were identified as independent variables with the strongest association with haemophilic arthropathy at the ankle. Avenues for physiotherapeutic intervention have been identified with preventative screening tools and pre-habilitation programmes possible for young boys with haemophilia at risk of developing this debilitating condition.

Traumatic brain injury (TBI) is becoming more prevalent in an age of increased motorization and violence. The majority of patients are young adults previously in paid employment. Life expectancy is usually unaffected once past the acute stage of recovery. The reported statistics for successful return to work (RTW) vary from 15% to 77%. However no literature was sourced which examines or discusses the most central component of successful return to work rehabilitation for these individuals - what the individuals themselves have found to be of assistance from their experience of return to work rehabilitation in attempting to return to work. This study explored the lived experience of return to work rehabilitation from the perspective of individuals who had sustained TBI and who had actively engaged in a return to work programme as part of their rehabilitation. A phenomenological approach, with an interpretative focus was utilized to explore and obtain an enhanced understanding from data gained in semi-structured interviews conducted with ten participants. The interviews were audio-recorded. The position of the researcher was situated within the research, and a reflexive component was interwoven throughout the process. Interpretative Phenomenological Analysis (IPA) was undertaken to elicit themes to enhance my understanding. Findings formed five main themes; personal cost of lifestyle losses, impact of TBI on perceptions of RTW, factors impacting on engagement in RTW rehabilitation, participants' perceptions of assistive elements of RTW rehabilitation, impact of RTW rehabilitation on participant. Each master theme comprised a group of sub themes, discussed within the thesis. The meaning of work pre-morbidly for individuals who sustain TBI characterizes their social and familial roles and responsibilities. Upon attempting to RTW following rehabilitation the definition of work often changes in conjunction with the individual's world views and perceptions of self. Whilst RTW rehabilitation may be an important goal for the individual and his/her family, because he/she accesses rehabilitation through a community based service, other, external, factors often impact on their ability to fully engage in a RTW rehabilitation programme. Little acknowledgement of this is made by clinicians, and more flexibility and further additional one to one interventions during times of difficulty would be assistive in optimizing the chances of success for individuals. Whilst all participants in this study were able to verbalize positive experiences of the outcomes of RTW rehabilitation, none had returned to their previous employment resuming their previous roles. Thus the core message of this thesis is that the role of the occupational therapist in RTW rehabilitation needs to incorporate many elements including group rehabilitation, one to one rehabilitation and clinical liaison with work places. This can be potentially achieved through adopting Mosey's (1986) Acquisitional Frame of Reference as a working practice model. In addition, facilitated longterm peer and clinical support is required to ensure individuals maintain success in their attempts to RTW. Clinicians involved in this area of work need to work within an interdisciplinary team approach, recognise and assist with a defined grief reaction that presents in individuals when they attempt to RTW, and be flexible and accommodating in the delivery of RTW rehabilitation to patients.

This study has been undertaken in order to develop a new nanocomposite acoustic material via incorporation of multi-walled carbon nanotubes (MWCNTs) into the conventional damping material–polyvinyl acetate (PVAc). Usually MWCNTs are added into polymers to strengthen its stiffness only. Here, properties of stiffness and damping are both required for the cone/diaphragm to improve sound features of the speakers. The work provides perspectives on MWCNT covalent modification and the effect of MWCNT surface chemistry on the acoustic performance of the nanotube composites.

Age-related changes in the central nervous system (CNS) is a multi-factorial process involving subtle alterations to several subcellular systems, including a disturbance to cholinergic signalling that becomes a prominent feature in age-related neurodegenerative diseases (Giacobini, 1990). Previous work in the L. stagnalis nervous system highlighted synapse-specific alterations in subsets of neurons that are accompanied by a marked decline in feeding behaviour in chronologically aged animals (Arundell et al., 2006; Yeoman et al., 2008). To identify common elements that lead to a reduction in feeding behaviour, 2D Difference in-gel Electrophoresis (2D DIGE) analysis highlighted 49 proteins that were differentially expressed in the aged L. stagnalis CNS. Amongst them, three key protein groups involved in maintaining the cytoskeletal integrity, energy-dependent processes, and chaperones were significantly altered in the aged CBG. The expression level of cytoskeletal proteins such as tubulin and actin, putative chaperones such as 14-3-3, and kinases such as arginine kinase as well as mitochondrial proteins such as reductase were all significantly down-regulated in aged CNS (p < 0.05) and are well aligned with changes that are observed in normally aged higher vertebrates. This suggested that the alterations in functional neuronal circuits that accompany a reduction in feeding behaviour in L. stagnalis may encounter a similar set of biochemical challenges as those experienced in higher vertebrates.

The aim of the this study was to develop a moderate intensity, specific and safe homebased exercise programme and evaluate its effectiveness on fall risk factors in Portuguese people over the age of 65.

This thesis reports a phenomenological study of seven parents’ lived experience following the death of a twin in the perinatal/ neonatal period. It gives consideration to the issues important to the study. It provides a literature search to situate the study in the field of evolving bereavement theory and in the context of twin loss. A number of questions have been raised that led to the formulation of the research question (page 63). The descriptive phenomenological methodology adopted provides a framework for my ontological and epistemological positions. Through the method of analysis of the data from semi-structured interviews, the essence of the phenomenon was elicited and the fundamental structure was established.

Patients with major burns experience pathological changes which have been shown to influence the pharmacokinetics of antibiotics. Subsequently it has been demonstrated that conventional doses of some antibiotics given to patients with major burns may result in sub-therapeutic serum concentrations. The aim of this thesis was to identify antibiotics used to treat infection in critically ill patients with burns, and to develop dosage guidelines for those where data is lacking. A survey of antimicrobial use in burns centres in the UK was undertaken, leading to the identification of five antimicrobials to be studied further. Published pharmacokinetic values for gentamicin were used to develop dosage guidelines for extended dose administration. With vancomycin, current dose recommendations were reviewed for their appropriateness. Three more antimicrobials were identified where little or no pharmacokinetic data were available for patients with burns; meropenem, linezolid and colistin. A patient study was therefore set up where serum samples at steady state were collected from patients enabling the calculation of pharmacokinetic data. These were related to pharmacodynamic principles in order to propose dose recommendations.