Embolic materials for the treatment of hypervasularised tumours are often non-degradable hydrogels. In this thesis alginate hydrogel microspheres were synthesised and tested as a potential biodegradable embolic agent. Degradation and compressibility were shown in vitro to be dependent on the mannuronic acid to L-guluronic acid ratio, which was attributed to the affinity of calcium to bind to the different alginate monomers. The microspheres were shown to be deliverable and compatible with non-ionic radiopaque contrast media.

This thesis is concerned with the concept of undergraduate Interprofessional Education (IPE) as a possible model of practice for the education of health care professionals at the Faculty of Health Sciences, University of Malta. In 2010, the World Health Organisation published its Framework for Action on IPE and Collaborative Practice outlining a vision for a “collaborative practice-ready workforce” emphasising the importance of the health and educational systems as supporting pillars of IPE and collaborative practices (WHO, 2010, p.7). The concept of IPE had been mentioned in policy documents in Malta but no such model had ever been tried or tested at the University. This study aimed to explore stakeholders’ perspectives and perceptions of IPE and to encourage debate of adopting such an approach at the Faculty of Health Sciences. This thesis starts by tracing a history of IPE internationally, teasing out the diversity of policy drivers and motivating factors behind its inception and highlighting the lessons learnt for its development and sustainability into curricula; which, inter alia, include the importance of political drivers, national coherent policies, organisational support and earmarked central funding. This was crucial to underscore as it brought to the fore the paucity of such triggers for IPE within this research study. The study then adopts a qualitative case study approach underpinned by a social constructionist and interpretative stance designed to explore the possibility of IPE at the University of Malta. The purposive sample totalled sixty four participants and these included academics at the Faculty of Health Sciences, key informants from the education/health sectors and newly qualified health professionals. Data was gathered through a combination of focus group discussions and one-to-one interviews, and analysed using Ritchie and Spencer’s (1994) ‘Framework’ analysis supported by NVivo software. Findings yielded rich insights into participants’ perceptions of IPE; while they lauded the notion in principle, they identified a multiplicity of factors that would pose barriers to its enactment in practice. Some barriers might be described as symbolic while others were rooted in the practical domain of operational systems and structures. On a symbolic level, participants were particularly concerned that IPE would pose a threat to their professional identities and to the maintenance of boundaries that define the conceptual territories of the various professions. Participants also pointed to traits and behaviours they perceived as endemic in Maltese culture that would conflict with the enactment of IPE; these were especially relevant as the influence of macro cultural determinants has been largely overlooked in the interprofessional literature. These findings were interpreted through an interdisciplinary conceptual framework drawing on sociological discourses of professionalism and Bourdieu’s theories of societies and social practices. The framework also drew on concepts in anthropological discourses, focusing in particular on Hofstede’s theory of cultural dimensions as a means of theorising about the role that national culture can play in shaping perceptions and behaviours. The originality of this study lies in its a priori approach by exploring perceptions of an interprofessional model of practice when this philosophy had not yet been considered, and which in the process, identified contextual variables which could impact on the design and delivery of IPE. It is unique in employing various theoretical perspectives so as to transcend the factual findings and engage in higher order reconceptualisation. It is also the first study of IPE to be conducted in Malta; significant to consider for any potential interprofessional initiatives. This research contributes to the body of evidence underpinning IPE in two ways. It highlights again the existence of embedded hierarchies and power struggles across health systems and how these impact on IPE, and it uncovers the potential impact of national culture as a tangible determinant in the planning, development and delivery of IPE initiatives.

Many conventional biomaterials fail to meet the demands required of them with respect to their surface and bulk properties. This problem can be addressed by developing novel biomaterials that have the desired bulk properties and increased biocompatibility. Alternatively the surfaces of biomaterials which have the desired bulk properties can be modified to increase their biocompatibility without compromising these bulk properties. Phosphorylcholine (PC) based coatings mimic the surface of biological membranes and so offer a novel method for modifying bulk materials, or can be incorporated into novel bulk biomaterials. One of the key issues of biocompatibility is the continual stimulation of the inflammatory response by biomaterials characterised in part by complement activation, macrophage adhesion and granulocyte activation.

Clinical reasoning refers to the process in which practitioners, interacting with their patients, structure meaning, goals, and health management strategies based on clinical data, patient/client choices, and professional judgment and knowledge (Higgs & Jones, 2000, p. 11). Recent literature in physiotherapy and other allied health professions describes clinical reasoning as moving between cognitive and decision-making processes required to optimally diagnose and manage impairment and physical disabilities (hypothetic-deductive), and those required to understand and engage with patients' experience of disabilities and impairments (narrative reasoning). Clinical reasoning has been described as a universal process, common to all clinicians, in particular in the musculoskeletal area. However, clinical reasoning models emerged from research developed in specific and well-developed health care and professional cultures, such as Australia and United States, but there has been little discussion of their relevance and applicability to other cultural groups. Since research literature concerning physiotherapy in Portugal is almost non-existent, the aims of this study were twofold. The first aim was to explore clinical reasoning processes in a sample of Portuguese expert physiotherapists and secondly, to identify the current perspective of clinical reasoning held by educators and students, and how it is promoted in the undergraduate curriculum. The focus of the study was musculoskeletal physiotherapy. The research was influenced by the interpretative/constructivist paradigm of inquiry. The study consisted of three parts. In part one, the clinical reasoning approach of a sample of Portuguese expert therapists in musculoskeletal physiotherapy was investigated. The study focused on Portuguese clinicians' interaction with their patients in order to define and manage clinical problems. Data was collected through non-participant observation, semi-structured interviews, memos and field notes, and analysed thematically to identify and compare the practice and reasoning approach used. In part two, the generic aspects of undergraduate physiotherapy curricula in Portugal were analysed to provide a first insight of how educational programmes are organized and delivered in Portugal. Then, current musculoskeletal physiotherapy curricula in Portuguese entry-level physiotherapy programs were analysed by a questionnaire survey and documentary analysis. The specific aim was to capture the educational process and actions underlying current educational practice across undergraduate courses. In part three (Study 3 and 4), a sample of musculoskeletal lecturers and a sample of near graduate students were selected against criteria relating to the diversity of institutions that offer undergraduate physiotherapy courses (private versus public institutions) and length of time as a Physiotherapy education provider. Each course was examined from lecturer and student perspectives (through individual interviews and focus groups) to see what kind of clinical reasoning approach were most emphasised in relation to physiotherapy intervention in musculoskeletal conditions. Data were transcribed and subjected to thematic analysis. Findings showed some similar characteristics in the reasoning process of this group of Portuguese expert physiotherapists in the study when compared with other studies in the musculoskeletal physiotherapy field. However, findings also highlighted that Portuguese physiotherapists were more likely to use and value an instrumental approach to clinical practice. There was little evidence of patients sharing their perspectives about their problems or participating in clinical decisions made. An instrumental approach to reasoning and practice was also dominant in current Portuguese musculoskeletal programs as well in educators' and students' perspectives. The focus was on diagnostic and procedural strategies of reasoning with little emphasis on promoting student competences to involve patients in the decision making process. In this sense, the practice and reasoning of this sample could be seen as more instrumental than communicative. Perspectives on clinical reasoning differ between cultures and contexts of practice and this has implications for the quality of health care education and service delivery. This research has identified the current model of clinical reasoning in Portuguese Physiotherapy practice. The findings have significant implications for clinical practice in musculoskeletal physiotherapy, curriculum development, and wider education and health service policy.

This study explores the role of the contemporary ward manager in the NHS. Using a grounded theory methodology, 9 ward managers and 32 other clinical staff participated in semi-structured interviews. In addition, ward managers were observed in practice on eight occasions. A pragmatist philosophical tradition informing symbolic interaction guided the interpretive analytical framework to generate a substantive theory of the role of a modern day ward manager through the analysis of their narratives and by observing them at work. The simultaneous collection, coding, memoing and analysis of the data, together with the body of existing literature, enabled a process of theoretical sampling to build an emerging theory of identity and agency.

One of the causes of ageing is thought to be the accumulation of senescent cells. Since normal ageing is very complex, diseases with single gene mutations (progeroid syndromes) which show many features of normal ageing have been used as models in ageing research. Werner's syndrome is the progeroid syndrome which mimics most of the features of normal ageing. It is caused by a mutation of the WRN gene that encodes a RecQ helicase/exonuclease involved in DNA fork stabilization and repair during synthesis. Werner's syndrome fibroblasts have been shown to exit their replicative lifespan three to five times more rapidly than normal fibroblasts. The mechanisms of Werner's syndrome senescence have been extensively studied in fibroblasts. However, it is clear that accelerated replicative senescence is not a universal feature of the disease in all tissues. Thus, it is important to study the relationship between Werner's syndrome senescence in different tissue lineages. Donor to donor differences in replicative potential are also known to occur, thus it would be advantageous if replicative lifespan could be studied in cells with isogenic backgrounds. Accordingly, this thesis describes an attempt to knockdown the WRN gene III normal cell lines to produce WRN-1- isogenic cell lines. RNAi knockdown using shRNA and hammerhead ribozymes was carried out previously but did not demonstrate a reduction in protein levels. However, an increased sensitivity to camptothecin was demonstrated by Comet assay. Therefore, we expressed both the shRNA and the ribozyme in a single cell line in order to improve the knockdown. The work was initially carried out on cell lines to test whether the RNAi method was effective prior to applying it to irreplaceable primary cell strains. This would have helped elucidate whether premature senescence in Werner's syndrome fibroblasts is due to DNA replication fork stalling or due to telomere erosion. In normal individuals, keratinocyte senescence has been shown to occur by either telomere dependent or independent senescence depending on culture conditions. Thus, we have used keratinocytes from Werner's syndrome to explore the relationship between loss of WRN and replicative senescence in vitro. This was carried out using standard cytokinetic tests in the presence and absence of SB203580, a selective inhibitor of p38 MAP kinase which plays an important role in Werner's syndrome fibroblasts.

Previous research has suggested that critical care nurses' close and prolonged contact with patients places them in a unique position of improving patient outcomes and reducing the demand on critical care beds by detecting subtle signs of deterioration in a timely manner and identifying patient progression and readiness for less intensive care. Nonetheless, nurses rarely take decisions about patients' treatment modalities on their own, and constantly need to seek advice or authorisation. Indeed, several studies suggested that one of the most frequent decisions taken by nurses during clinical practice is that of referring to medical, nursing or other health care practitioners. However, there is very Iim ited research around the factors related to, and the actual process of, such referring. In view of this gap in the literature, the purpose of this study was to explore and explain the process of referring in the context of an intensive care unit by means of a substantive theory derived from the data. The principal research question was: What are the factors associated with critical care nurses' decisions to seek help from medical practitioners? The study took place in a general intensive care unit in a state hospital in a Mediterranean island nation. Data generation and analysis took place concurrently and iteratively, and were guided by the dimensional analysis approach to grounded theory. Data collection involved : (1) twenty hours of preliminary non participant observation; (2) fifty hours of participant observation and informal interviewing; (3) fifteen hours of formal semi-structured interviews with ten critical care nurses working in this unit selected by means of purposive and theoretical sampling; (4) two 2-hour focus group sessions aimed at enhancing theoretical sufficiency and verification of the emerging substantive theory. The analytical process was characterised by a series of inductive-deductive cycles, during which increasingly conceptual labels were attached to data segments. Working hypotheses and theoretical memos were used to interrogate the data and look for positive and negative evidence for the inductively derived labels. The findings suggest that nurses' decisions to seek help from doctors are complex and frequently mediated by individual or organisational factors which are unrelated to the actual clinical situation, such as experience, asse11iveness and willingness to take risk. They involve nurses weighing up several occasionally conflicting motivators, including a desire to act with some degree of independence; attempting to prevent personal and professional risk; and being constantly mindful of their asymmetrical decision making power relative to doctors. A central consideration is that of balancing their moral obligation to safeguard critically ill patients' interests with their duty to respect medical practitioners' preferences. Subsequently, nurses find themselves in a position of dual agency as they need to concurrently act as an agent to two different principals, namely the medical practitioner and the patient, a situation which is potentially morally distressing. The emergent substantive theory underscores the significance of the nurse's role in acting on behalf of the patient in a scenario of significant patient vulnerability; the factors that enhance, mediate and potentially suppress this advocacy role; and the interrelatedness of nurses' relationship with doctors and their effectiveness in safeguarding critically ill patients' interests. Subsequently, the study should provide valuable insight into the type of leadership and education that is required to assist nurses in placing patients' interest at the forefront of their actions and interactions, while fostering collaboration within multidisciplinary teams.

Beta-cell survival is low following islet transplantation and this may be linked to a delay in revascularisation of donor cells. This decrease in oxygen supply is termed hypoxia, the result of which is detrimental to beta-cell survival. The current research sought to investigate post-transplant beta-cell viability and function by investigating the effects of low oxygen levels on MIN6 pancreatic beta-cells. MIN6 beta-cells were exposed to 1% oxygen (hypoxia) or 21% oxygen (normoxia) over a period of 72 hours. Viability was assessed by MTT assay and cell number was determined by haemocytometer count at 0 hours (normoxia), 24 hours, 48 hours and 72 hours. A Hoechst propidium iodide (HPI) stain was used to identify beta-cell apoptosis or necrosis during hypoxia. Western blot analyses were performed to determine the PI3K, pAkt, pAMPK, PDX-1, GLUT2 and pS6K protein levels. Real time PCR was used to estimate glut2, vegf, hif and insulin gene expression by MIN6 cells following exposure to hypoxia over various time points.

Statutory wheelchair provision in England and Wales has been equipment led since its inception in 1990. However, users are reported to be dissatisfied with the service and a reorganisation of provision is underway that purports, in accordance with recent Government advice (DOH, 2012), to make the wheelchair user central to the supply process. However, little is known about wheelchair users perspectives of the equipment that they use to inform this process.

There has been considerable debate over the optimum age of introduction of solid foods in infants and particularly its association with nutrient and iron adequacy for growth and development as well as its impact on eating behaviours, such as feeding difficulties, dietary variety and food preferences. Since infants and toddlers are at a higher risk of developing iron deficiency anaemia, a non-invasive method of measuring haemoglobin could be a useful tool in identifying low haemoglobin levels early and prevent further deterioration of iron status. Since the adoption of the World Health Organisation (WHO) recommendations for exclusive breastfeeding for 6 months, there has been limited data in the UK about how the new guidelines have affected the growth, eating behaviours, dietary intake and iron status. This thesis aimed to address these gaps in the literature in 3 studies: the Brighton’s Breast-fed Babies Study, the Haemospect® Validation Study and the GO-CHILD Study.