Oxidised bases in DNA are removed by a number of DNA glycosylases in the first step of base excision repair. These include 8-oxoguanine DNA glycosylase (OGG1), endonuclease III-like 1 (NTH1) and the Nei-like proteins, NEIL1, NEIL2 and NEIL3. While NEIL1 and NEIL2 are relatively well characterized, the function of NEIL3 is still not fully understood. Although all three proteins show homology to the Escherichia coli Fpg/Nei family, NEIL3 is the largest member with an extended C-terminal domain and contains a valine instead of the highly conserved proline residue at amino acid position two. While it has been reported that recombinant murine NEIL3 shows DNA glycosylase and AP lyase activities in vitro, its biological role remains unclear. Therefore, to gain an insight into the function of NEIL3 in vivo, the full-length human NEIL3 cDNA has been expressed in Saccharomyces cerevisae as a prelude to undertake a yeast 2-hybrid screen to determine specific protein-protein interactions. To date, cDNA library screenings for potential hNEIL3 interactors have been completed and clones expressing potential interactors have been isolated, sequenced and analysed. This data, along with the results of other confirmatory experiments are presented in this thesis. Furthermore, clones of Pichia pastoris harbouring an expression cassette with full-length human NEIL3 or mouse NEIL1 or truncated versions of hNEIL3 with amino acid length 1-394 and 1-502 cDNA have been generated in preparation for its overexpression in a eukaryotic system. It is envisaged that the expression of 6XHis tagged hNEIL3 in P. pastoris will enable the purification of hNEIL3 protein that can be used in enzyme assays and for further in vitro investigations of putative protein interactions discovered by yeast two-hybrid (Y2H) screen.

Background In Saudi Arabia, more than 2 million people complain of asthma: 13% being aged 6-10 years. This makes asthma one of the most common illnesses among children in Saudi Arabia. Little has been explored about children’s ability to learn more about their own asthma in Saudi Arabia. Aims The study was designed to assess the impact of a school-based, nurse-delivered asthma health education programme on asthmatic children's knowledge and attitude towards asthma, quality of life, anxiety level, and school absenteeism. Methods A quasi-experimental, non-equivalent group, pre-test post-test design was used. The education programme was developed from existing evidence. The Paediatric Asthma Quality of Life Questionnaire, Spence Anxiety Tool, Asthma Knowledge Questionnaire, and Asthma Attitude Questionnaire were employed for data collection in 2013. Intervention (n=130) and control (n=98) groups were drawn from 10 schools in Ha’il region, Saudi Arabia. Both descriptive and inferential statistics were used to examine differences between groups. Results The level of asthma knowledge was increased significantly more in the intervention group than in the control group (F=26.5746, DF 2, p<0.001). Attitude toward asthma was not changed by the intervention (F=0.0490, DF 2, p=0.9522). In the accumulative score, there was a statistically significant difference in the anxiety score between the three phases of intervention group (F=3.7599, DF 2, p=0.0242) but no statistically significant difference between pre-test and either post-test (p>0.05). Anxiety scores had reverted to those at pre-test at post-test II. Regarding quality of life, the intervention group scored higher in total quality of life scores compared to the control group (F=87.6534, DF 2, p<0.001). Finally, school absenteeism also reduced significantly after delivering the programme (F=2.98, DF 2, p=0.003). Conclusion The asthma education programme impacted positively on students' knowledge, anxiety, quality of life, and school attendance. However, asthma education did not change attitudes towards the condition. The results emphasise the benefits of provision of health education directly to children. Asthma education should be integrated into the Saudi national child health programme.

Self-care, capability in performing certain activity in maintaining well-being in daily life, is regarded important especially among people with long-term condition such as diabetes. Locus of control and religion are regarded as important factors in influencing such particular activity in day to day basis. Indeed, among Javanese people the lingering culture cannot be separated from religion, influencing how they perceive any factors that might play into role in managing any ill-health condition. Utilizing a mixed methods study design, with the deployment of two screening tools for further semi-structured interviews (the Summary of Diabetes Self-care Activity and the Muslim Piety questionnaires), this study was aimed to explore further into the perceptions and experiences of Javanese Muslim with diabetes in utilizing religion with embedded cultural aspects, in managing their daily self-care activity. Subsequent to this, the study sought further into barriers and opportunities in performing self-care. A convenient sample of 100 participants has filled the questionnaires, and 24 participants from various gender and age groups were purposively collected to gain a richer perspective for further interviews. The study identified the moderate self-care practices as a separate notion, instead of an integrated and comprehensive concept. The study has also found that the act of surrendering or nerimo ing pandum among Javanese people, as a representation of external locus of control, is paramount in maintaining self-care. The state of surrendering has been shown in the belief in Allah as the determinative factor in managing self-care, and in how they were surrendering to the lacking of adequate access to healthcare services. Social support can be served as a hindrance in self-care, as well as supporting factor. The later notion has been shown in the role of Pengajian, a social religious activity, and Persadia, a peer support group, which have been performing more of a social hub in supporting not only in enhancing capability, but also psychological support. The role of external locus of control and the lack of healthcare access have been served as an opportunity in conducting an individualized approach in educating the Javanese Muslim in enhancing the capability and capacity in self-caring themselves, with collaborative work between the healthcare professional and the Muslim cleric.

In the diverse linguistic landscape of England, it is not uncommon for social workers to work with families who possess varying degrees of English language proficiency. Within such families children may speak multiple languages, and have greater English language proficiency than their parents. The study involved two areas of inquiry. The first part of the inquiry included semi-structured interviews with child and family social workers (n=9), to explore their experiences of interpreter–mediated encounters, including the use of children as interpreters. The second part focused on child language brokering (CLB), this refers to young people who translate and interpret for adults who do not share a mutual language. This part of the research took place at a youth centre and involved semi-structured interviews with young people (n=9) to explore their experiences of language brokering for various adults in multiple settings. The research draws on social constructionist theorising to describe and analyse the participants’ experiences of interpreting. Child interpreters were found to be used by social workers as an informal interpreting resource, to compensate for inadequate linguistic provision. The research presents four challenges in social work practice: i) providing adequate interpreting provision for service users with limited English language proficiency; ii) working effectively with interpreters; iii) working with families in which children speak more English than their parents; and iv) protecting children from the perceived harm of interpreting. The findings from the young people illuminate CLB as one activity that enables persons with limited English language proficiency to access services in the community. CLB therefore presents a diverse conceptualisation of interpreting, childhood and intergenerational relations between children and adults. The findings from both datasets illuminate different aspects of interpreting encounters; social workers as recipients of interpreting provision and young people as providers of interpreting. These dual perspectives illuminate a taken-for-granted area of social work practice and social life.

Introduction: Asthma is the most common long-term illness in children and for the majority of these children asthma continues into adult life. Therefore, developing good decision-making skills at a young age could optimise long-term health outcomes. There is a paucity of research that examines how a child and their parent may share decisions with respect to asthma management, particularly from the child’s perspective. Methods: A qualitative descriptive study that explored who, what, when and why asthma management decisions occur and are shared between children, 7 to 11 years of age, and their parents. Seventeen participants were recruited, 8 children, 8 parents and 1 grandparent. Data was captured undertaking in-depth individual interviews, using an arts based activity at the beginning of the child interviews to build rapport with the child. Framework approach underpinned data analysis. Findings: A dynamic model of the way children and parents transfer, shift and share asthma management decisions was uncovered. A conceptual framework was initially developed from the theoretical perspectives relating to child and parent shared decision-making and subsequently revised to integrate findings from the data analysis of the children’s and parent’s accounts. Conclusion: The thesis uncovers new knowledge that asthma management decisions between children and parents are non-linear, with responsibility transfers from child to parent under different conditions; whether the child or parent dominates, across contexts and individual child/parent preferences. Understanding the shifting/sharing process of decisions has the potential to assist health care professional practice to support child-parent decision-making in asthma, working with the family and as the child develops.

Introduction: Many older people presenting to Acute Medical Units (AMUs) are discharged home after only a short length of stay, yet research has found that many re-present to hospital within a year. This constructivist study explored patient and informal carer views of care and treatment received on an AMU whilst participating in a trial of a specialist geriatric intervention. Method: Eighteen older patients and six of their informal carers were purposefully selected from the above trial. These participants were interviewed in their homes up to six weeks following discharge. An interview guide was used to encourage participants to provide both narratives and their opinions and views around the AMU stay, and the resettlement period back home. The data were analysed using two analytic approaches: thematic and narrative analysis. Results: The analysis revealed five major themes. These revolved around participants making positive comments about the AMU staff, whilst also revealing an underlying subtle message that things could be better. The participants were similarly positive about the geriatricians, but were unable to articulate what had been done for them. On discharge, the patients had both outstanding health and daily living needs, which were not resolved by the admission. These needs impacted on their informal carers, who supported them with their daily living activities. Overall these participants were stoical and had low expectations of hospital care. Conclusion: The study has provided an in-depth understanding of the older patient and informal carer experience of an AMU stay. The recommendations made revolve around meeting patient’s basic physiological needs, improving staff communication with both patients and their informal carers, and improving the on-going care management of these patients post discharge, including further medical review and rehabilitation.

Aim of research: This research aimed to design and develop a synthetic anthropomorphic breast phantom with cancer mimicking lesions and use this phantom to assess the relationship between lesion visibility and breast thickness in mammography. Due to the risk of cancer induction associated with the use of ionising radiation on breast tissues, experiments on human breast tissue was not practical. Therefore, a synthetic anthropomorphic breast phantom with cancer mimicking lesions was needed to be designed and developed in order to provide a safe platform to evaluate the relationship between lesion visibility and breast thickness in mammography. Method: As part of this research custom Polyvinyl alcohol (PVAL) breast phantoms with embedded PVAL lesions doped with contrast agent were fabricated and utilised. These breast phantoms exhibited mechanical and X-ray properties which were similar to female breast/breast cancer tissues. In order for this research to be useful for human studies, patient safety factors have constrained the extent of this research. These factors include compression force and radiation dose. After acquiring mammograms of phantoms with varying thicknesses, the image quality of the embedded lesions were evaluated both perceptually and mathematically. The two-alternative forced choice (2AFC) perceptual method was used to evaluate image quality of the lesions. For mathematical evaluation the following methods were utilised: line profile analysis, contrast-to noise ratio (CNR), signal-to noise ratio (SNR) and figure of merit (FOM). Results: The results of the visual perception analysis of the mammograms demonstrate that as breast compressed thickness reduces the image quality increases. Additionally, the results display a correlation in the reduction in the level of noise with the reduction in breast thickness. This noise reduction was also demonstrated in the profile plots of the lesions. The line profile analysis, in agreement with visual perception, shows improvement of sharpness of the lesion edge in relation to the reduction of the phantom thickness. The intraclass correlation coefficient (ICC) has shown a great consistency and agreement among the observers for visibility, sharpness, contrast and noise. The ICC results are not as conclusive for the size criterion. Mathematical evaluation results also show a correlation of improvement in the image quality with the reduction in breast thickness. The results show that for the measures CNR, SNR, and FOM, the increase in image quality has a threshold after which the image quality ceases to improve and instead begins to reduce. CNR and FOM dropped when the breast phantom thickness was reduced approximately 40% of its initial thickness. This consistently happened at the point where the filter changed from rhodium (Rh) to molybdenum (Mo). Conclusion: This breast phantom study successfully designed and developed an anthropomorphic compressible breast phantom with cancer mimicking lesions with mechanical and X-ray properties similar to human breast tissue. This study also demonstrates that as breast compressed thickness reduces the visibility of the perceived lesion increases. The radiation dose generally decreases up to the point that the filter changes from rhodium to molybdenum. After this point, the radiation dose increases regardless of the phantom thickness. The results from this thesis are likely to have implications for clinical practice, as they support the need for compression/thickness reduction to enhance lesion visibility.

Background Proper management of pain is necessary to help patients recover quickly during postoperative care. Failure to promptly assess and manage pain could lead to complications in postoperative situations and can also increase the length of required hospital stays, create or add to elements of chronic post-surgical pain and overall poor health outcomes for the patients. Nurses play crucial roles in assessing postoperative pain, however despite advances in nursing care, there is evidence from a range of research which suggests that patients still suffer considerable levels of postoperative pain. In Kuwait’s healthcare setting, there is a paucity of literature on how nurses perform pain assessment and whether this leads to significant pain relief amongst patients. This research addressed this apparent vacuum in current research literature by exploring the experiences of nurses and patients in Kuwait in postoperative scenarios – focusing in particular on postoperative pain. This work also utilised the findings to help to provide a suggested framework through which the quality of care received by patients in surgical wards in Kuwait could be improved. Aims and Objectives This study aimed to explore how Kuwaiti nurses assess pain in postoperative patients in hospital settings in Kuwait and also to examine postoperative patients’ self-reported experiences of pain. Specifically, this study aimed to address the following objectives: - To explore the roles and responsibilities of surgical nurses in postoperative pain assessment; - To determine the knowledge and perceptions of nurses working in Kuwait on pain assessment; - To investigate the postoperative pain experiences of patients in surgical wards; and identify potential factors that could affect how patients respond to postoperative pain. This was intended to help to provide a framework for dealing with the main aim of this thesis which was to look at how nurses assess postoperative pain in Kuwait, and whether the current methods for doing so represented best practice when compared to other regions or institutions. Methodology This study utilises a qualitative methodology based on a Grounded Theory (GT) approach to social research. This encourages theory building throughout the work and is used to explore concepts relating to pain and how this is influenced by a range of socio-economic and cultural factors. In addressing these issues the experiences of nurses and patients in a hospital ward in a Kuwaiti hospital was established as the research case study. Ten nurses and ten patients were invited to take part in the study through purposive sampling techniques outlined within a grounded theory approach. Inclusion and exclusion criteria were established to ensure that only adult patients aged 18 years old and above who will give their informed consent to participate in the study would be included. Nurses who have at least one-year experience in a surgical ward were also invited to take part in the study. Data Analysis Data was analysed through a grounded theory approach based on key elements of the models espoused by Strauss and Corbin (2008) and Charmaz (2006). This began with a process of data familiarisation once the interviews had taken place, followed by processes of axial and open coding, selective coding, and the generation of categories and themes. In accordance with the grounded theory methodology data analysis and collection of data occurred simultaneously. The main aim of the data analysis was to help generate theories that explain the nurses and patients’ experiences in pain assessment during postoperative care in Kuwait’s healthcare setting. Results and Recommendations The research found evidence to suggest that many patients in the Kuwaiti healthcare system in postoperative scenarios are experiencing difficulties in addressing issues relating to postoperative pain. This was evidenced by patient participants in the study who felt de-legitimised and an undercurrent of distrust between the nurses and the patients. This was mirrored in the responses of some nurses, who also expressed concern that some patients were exaggerating their pain - determining their own opinions and perhaps devaluing the direct experiences of the patients themselves. In addition the research suggests that there are ongoing social power issues in Kuwait and an apparent lack of autonomy which is creating a culture of blame. Although there are clear resource issues, it is apparent that this lack of autonomy and the levels of distrust between patients, nurses and doctors need to be addressed urgently to ensure that postoperative pain care in Kuwaiti hospitals is improved. In Kuwait these issues of a lack of autonomy and an apparent lack of focus on the subjective nature of pain in relation to robust assessment methods has manifested as a cultural norm. As a result there is a need to begin to address formal education of nurses, the level of power and autonomy given to nurses and the establishment of standardised pain assessment procedures more rigorously and definitively. This can be achieved by ensuring that the nurse-doctor professional relationship is improved through better communication structures, more effective training programmes in treating pain, and by challenging a culture where patient’s opinions and feelings on pain are not addressed by medical professionals. This study has provided evidence based data sets which can be utilised in further developing the nursing curricula in Kuwait across both undergraduate and postgraduate nursing programmes and also across many aspects of in-service education within the hospital units themselves.

The intensive care unit (ICU) embodies an environment of advanced technology and care, collaborative decision making and life-threatening emergencies. Critically ill patients are central to this unique milieu and culture, cared for by knowledgeable and skilful nurses who manage each patient’s intensive care journey. Highly developed decision making skills become essential as life and death are often finely balanced. In the United Kingdom, once the decision to withdraw life-sustaining treatment has been made by the medical team, further decision making relevant to the actual withdrawal of treatment is conducted by nurses. The aim of this study was to explore critical care nurses’ experiences following the decision to withdraw treatment from patients in a UK intensive care cultural setting. An ethnographic lens of enquiry was the chosen methodology, and methods employed included 144 hours of observation and eight semi-structured interviews (using two vignettes) developed from the ICU experience. The research was conducted in a large 20 bed ICU in the North West of England. The participants were qualified nurses who met the main inclusion criteria of the study in that they had all experienced caring for a patient following the decision to withdraw treatment. Data analysis was undertaken using Ricoeur’s analytical framework. Three central themes emerged from the data analysis, namely: the decision to withdraw treatment; nurses’ actions following the withdrawal of treatment decision; and shared experiences in the journey towards death. The findings suggested that nurses’ created a private space for the dying patient and discovered a parallel journey towards death experienced by the patient, the nurse and the family. The nurse’s adaptation from a curative focus of care to palliative care also emerged, where the desire was to offer positive and meaningful experiences for the family during this emotive phase of ‘end-of-life care’. Recommendations for clinical practice include the recognition of the value and benefits of formal and informal support for nurses during the patient’s withdrawal of treatment and subsequent dying trajectory. Recognition of the importance of the intensive care environment as a whole for dying patients, their families and their care cannot be undervalued. In addition, given the palliative nature of care required of critical care nurses, a recommended of the inclusion of a palliative care specialist nurse in the multi-disciplinary team could enhance the patients’ quality of end-of-life care.

Amputee gait is characterised by a higher metabolic cost of walking compared with anatomically intact subjects. Anatomically intact gait kinetics reveals that tendons crossing the ankle joint store and return strain energy during the stance phase of walking to provide forward propulsion. One of the main reasons for the high-energy cost of amputee gait is that passive prosthetic feet store little energy compared with the equivalent human structure and hence cannot provide the required energy at push-off. In addition, passive prosthetic feet are uncontrolled in the storage and release of strain energy, and do not provide natural levels of resistance and propulsion. Therefore, designing a passive prosthesis to efficiently store and transfer energy between joints, with continuous control over ankle torque, remains a research challenge. With the aim of developing an energy efficient passive prosthesis capable of mimicking the controlled energy recycling behaviour seen in an anatomically intact limb, a hydraulics-based design was investigated in this work. A first design concept, based on a hydraulic accumulator, a variable displacement hydraulic actuator (VDA), a gearbox, and a low-pressure oil tank, was developed. The accumulator served as energy storage medium, where VDA served as the only actuator to provide ankle torque. Simulation showed that the design outperformed commercial passive prostheses as well as a recent novel design based on a spring-clutch mechanism. For level walking, it provided 86% and 69% of the peak power required by the anatomical ankle whilst providing near normal ankle torques. The system was able to store all of the available energy during gait and provide correctly timed release of energy. However, a feasibility study showed problems with size and weight of a potential prototype. To address this problem a second design was developed with the aim of reducing the size and weight of VDA in design I. The second design comprised of a spring to provide ankle torque and to reduce the torque load on the VDA. The spring is connected to the ankle via a lever arrangement, and the VDA is used to vary the lever arm to continuously control ankle torque. Simulation results showed that design II outperformed design I; it delivered higher values of peak power, and a feasibility study showed that, using bespoke component designs, it might be possible to incorporate it into a lower limb prosthesis.