Charcot-Marie-Tooth disease (CMT) is a peripheral neuropathy presenting with distal weakness and sensory loss. This thesis examines the role that proximal activity plays in compensating for distal weakness to maintain functional walking. Comparative 3D gait analysis showed reduced range of ankle motion kinetics in people with CMT. Additionally, swing phase hip flexion increased, moments and power around the knee altered during preswing and trunk motion increased. These changes were related to the degree of distal weakness. Proximal adaptations were also observed in healthy control subjects following isolated bilateral fatigue of the plantarflexors but did not resemble those of people with CMT. The role the hip flexors play in compensating for plantarflexor weakness to maintain walking was examined in two studies. When walking on a treadmill people with CMT took an average of 48 minutes to reach level 17 on the Borg perceived exertion scale whereas matched control subjects reached level 8 while walking at the same speed and cadence. After prolonged walking the maximum voluntary contraction of the hip flexors reduced by 20% in the CMT group. Additionally, hip flexor velocity reduced during swing phase and trunk motion increased. A separate study specifically fatigued the hip flexors by 20% resulting in similar kinematic changes to the first study, plus a reduction in walking time to reach Borg level 17 in people with CMT. The effect of ankle foot orthoses (AFO) was investigated in people with CMT. A variation in the stiffness of the three splints was observed when worn with footwear. During walking all AFOs reduced footdrop during swing phase but did not reduce hip flexion. One of the more rigid devices also reduced the total ankle power generation during preswing. These studies suggest that proximal compensations are present, they maintain functional walking and may be influenced by orthotics intervention.

The words 'competence' and 'capability' are used independently by the human resource managment and the strategy communities who relate the terms to people and organisations respectively. However, the linkage between the individual and organisational level is not well documented. A better understanding of this link is important in being able to understand how organisational and individual performance may be improved but also why things sometimes go wrong. This research based case study is to identify the linkage between individual and organisation capability through an examination of patient care provided by dcotors in St George's Hospital, Tooting, London using the perspective of the resource based view of the firm. The research showed that patient care is achieved through the emergent skilful exploitation by doctors of their own capabilities, interaction with others, an their use of artefacts representing technical systems, processes, and structural influences within which the doctor operates. The role of artefacts is particularly important because continuity of patient care is dependent on information provided via artefacts rather than doctors' individual knowledge of particular patients. Doctors need not only medical knowledge but also an understanding of 'how to work the organisation'. that is how to get the organisation to do what the doctor needs for the patient. Competent action of the hospital is dependent on a series of inter-relating and inter-locking activity systems, from the doctor carrying out direct actions for a patient through the operation of departmental support systems to the overall hospital level patient care systems. Contradictions or non-copetence occurred when there was a breakdown within or between the systems. A conceptual model and diagnostic is developed that will be of use in analysing these dimensions of organisational capability.

Older people resident in care homes are amongst the most vulnerable and dependent in any society. This study aimed to explore perspectives on decision making in a care home in the United Kingdom (UK), considering the appropriateness of who made the decisions, how and under what authority. It used grounded theory methodology in a case study framework, in a single care home. Field work was conducted between December 2009 and January 2011 in an inner metropolitan area. Participants were twenty one residents, eight relatives, five registered nurses and six care workers. Data were collected using; interviews; informal conversations; observation and examination of documentation. Participants' perspectives were considered through a values based lens with emphasis on autonomy and dignity as the most dominant in policy, ethical discourse, professional and empirical literature. Findings were constructed from systemic analysis of the data. Two central phenomena were identified, resident as decision maker and others decide for resident. Decisions were categorised into three types, everyday, infrequent and advance decisions. Each group of participants viewed different decision types as most important. Staff appeared to have little knowledge of policy and law and notably, they appeared not to consider mental capacity in relation to decision making, nor did they demonstrate recognition of the ethical dilemmas they faced. All participants found it difficult to articulate values underpinning decision making. Despite staff accepting that residents were able to make decisions and had a right to do so, residents' preferences were not always respected. There was a tension between staff's desire to offer choice, the need to minimise risk and provide good care within the constraints of the organisation with a finite number of staff. If operationalised, the value of solidarity could help relieve the tension and potential dissonance experienced by actors in the care home under study and similar care home environments. Solidarity promised mutuality and reciprocity which would allow all actors to be recognised and valued, ultimately benefiting the residents' quality of life.

Volunteer mentoring (befriending and peer support) is provided across a wide range of services for people with varying health conditions. Despite such services for carers of people with dementia increasing in number, there is little evidence for the benefits they may offer. Using a pragmatic approach, this thesis investigated the impact of volunteer mentoring on carers. It also explored the processes by which volunteer mentoring works and the experiences of volunteers delivering the interventions, many of whom are former carers. A systematic review and survey of volunteer mentoring services highlighted conflicting findings surrounding the impact of the services, the perceived importance of experiential similarity of volunteers and matching carers and volunteers. However, reported outcomes from the systematic review and survey were more consistent, namely reducing emotional distress, loneliness and social isolation of carers. To explore these issues in greater depth, a sequential explanatory mixed methods design was adopted. Data were collected from carers using validated rating scales (HADS, MSPSS and the UCLA Loneliness Scale) and semi-structured interviews. Data collection from volunteers was by semi-structured interviews only. No statistically significant changes were found after the six month study period for anxiety, depression or loneliness for carers. However, significant differences in perceived social support scores were found (p = 0.042). Post-hoc analysis showed this to be between baseline and three months follow-up (p = 0.015). Of the three subscales of the MSPSS, only support from a ‘significant other’ was shown to be statistically significant between baseline and three months (p = 0.013). Qualitative findings showed volunteer mentoring to be an important source of emotional and social support for carers, which was facilitated by the volunteers’ experiential similarity. Similarly to carers, volunteers reported the importance of experiential similarity in developing bonds with carers. They discussed the importance of developing mutually beneficial relationships which leads to a two-way flow of support. Volunteers also reported satisfaction and enjoyment from their roles. Data integration showed volunteer mentoring can be a source of social support for carers. The statistically significant difference in perceived social support from a ‘significant other’ between baseline, three months follow up, was confirmed by carers taking part in the qualitative phase. They perceived that volunteer mentoring can help them be networked into other services and help them to cope better with their caring role. It is argued that volunteer mentoring is an important source of support for some carers and that the development of these types of services should be considered alongside other forms of social support. This was one of the first studies of its kind to investigate both the process of volunteer mentoring and its impact specifically on carers of people with dementia. It is concluded that without experiential similarity, carers and volunteers may not develop the level of trust necessary to form mutually beneficial relationships.

This thesis describes some models that attempt to forecast the number of occupied beds due to emergency admissions each day in an acute general hospital. Hospital bed managers have two conflicting demands: they must not only ensure that at all times they have sufficient empty beds to cope with possible emergency admissions but they must fill as many empty beds as possible with people on the waiting list. This model is important as it could help balance these two conflicting demands. The research is based on data from a district general and a postgraduate teaching hospital in South East London. Several tests indicate that emergency bed occupancy may have a nonlinear underlying data generating process. Therefore, both linear models and nonlinear models have been fitted to the data. At horizons up to 14 days, it was found that there was no statistically significant difference in the errors from the linear and nonlinear models. However at the 35 day forecast horizon the linear model gives the best forecast and tests indicate errors from this model are within 4% of mean occupancy. It is noted that a Markov Switching model gave very good forecasts of up to 4 days into the future. A search of the literature found no previous research that tested emergency bed occupancy for nonlinearities. The thesis ends with a gravity model to predict the change in number of Accident and Emergency (A&E) attendances following the relocation of an A&E Department in South East London.

The role of community pharmacy (CP) in health promotion has developed over the last decade and a half following the introduction of the new National Health Service (NHS) plan in 2000. CPs have been turned into healthy living centres where individuals can access a variety of services designed to prevent disease and promote health. In 2005, three types of pharmacy service were introduced; essential, advanced and enhanced (currently known as locally commissioned). Enhanced pharmacy services were provided by Primary Care Trusts (PCTs) (until 2010) based on local needs identified by PCTs. In 2010, the Government decided to abolish the PCTs by 1‘"t April 2013; hence, PCTs entered a transition phase between 2010 and April 2013. By February 2011, each PCT was required to publish Pharmaceutical Needs Assessment (PNA) report regarding the provision and need for pharmacy services. The national commissioned vascular and sexual health enhanced pharmacy services in England are Stop Smoking Service (SSS), NHS health check, Emergency Hormonal Contraception (EHC) and chlamydia screening and treatment services. In 2012, the Healthy Living Pharmacy (HLP) scheme, which was piloted in Portsmouth PCT, was expanded to 30 PCTs known as HLP pathfinder PCTs. The aim of this research was to identify the correlation between needs, provision and uptake of vascular and sexual health pharmacy services at a PCT and CP level. It also aimed to investigate whether the provision of those services was cost effective. Finally, it aimed to determine the impact of the introduction of the HLP scheme on the provision and uptake of those services. At a PCT level, the PNA reports were used to identify the CP provision of SSS, EHC service and chlamydia screening service for the financial year 2009/2010. The local need for SSS (prevalence of smoking adults) and EHC services (rates of teenage pregnancy) were obtained from Health Profiles for each PCT. The need for chlamydia screening service (prevalence of positive chlamydia infection) was obtained from the National Chlamydia Service Programme (NCSP). Uptake and cost attributed to provision of those services for the financial year 2009/2010 were obtained from a short questionnaire targeted the public health leads for the related services in PCTs where the provision of services and the needs were identified. Simple cost-effectiveness analyses were performed on CP SSS and CP EHC provision, based on identified uptake and cost. At a CP level, a cross-sectional survey was conducted on 1 249 CPs in 28 PCTs across England in 2013. PCTs were chosen based on provision of SSS, EHC and chlamydia screening service identified in the PNA reports. 7 PCTs out of 28 PCTs were HLP pathfinder PCTs. CPs were allocated to one of five groups based on deprivation. The response rates for SSS, EHC and chlamydia screening surveys were 30% (42/138), 30% (42/139) and 19% (21/111) respectively. Data analysis identified that the need for SSS and EHC services were highly correlated with deprivation, with Spearman's rank correlation coefficients (rho) of 0.76 and 0.83 respectively (both P 0.001). The correlation between deprivation and the need for a chlamydia service was weak (rho = 0.25, P = 0.009). Higher number of CPs per 25 000 population were observed in more deprived PCTs (rho = 0.63, P < 0.001). CP provision (percentage of CPs offering a service out of total CPs in a PCT) of SSS, EHC and chlamydia service did not correlate with needs. The uptake of SSS, EHC and the chlamydia screening service did not correlate with increasing need or deprivation. However, pharmacists in areas of higher need dealt with a greater number of clients in relation to SSS and EHC services to meet their local needs, with rho of 0.4 and P of 0.01 in case of SSS and Pearson's correlation coefficient (R) of 0.36 and P of 0.02 in case of EHC. A cost-effective analysis of CP SSS provision found it to be cost effective when compared to no intervention based on NHS perceptive and the incremental cost per Quality Adjusted Life Year (QALY) gained. was £1 511. Similarly, the CP EHC service was also found to be cost effective with an NHS saving of £689 per unintended pregnancy prevented. The response rate for the CP survey was 19.3% (241/1 249). No significant differences were identified in terms of provision or uptake of SSS, EHC, chlamydia screening and NHS health check services between CPs with different deprivation neighbourhoods. 18.5% (31/168) of the respondent community pharmacists were working in HLPs. The uptake of SSS through HLPs (median = 6) was higher than that through non-HLPs (median = 4; P = 0.02)._Playing a more active role in health promotion was cited as the main driver for pharmacists to adopt an HLP scheme. Respondent pharmacists indicated that the introduction of an HLP scheme had improved public awareness of vascular and sexual health services available in CPs and they suggested the use of social media websites to further improve public awareness. Lack of time and the provision of similar services via other providers were considered the main barriers. Local Authorities should increase the provision of vascular and sexual health pharmacy services to meet the needs of their localities. They should use the latest technology to improve public awareness regarding availability of those services in CPs.

Angiogenesis is essential for the growth of a tumour, as it provides tumour cells with nutrients and oxygen for their survival. As the tumour expands, neovascularisation is facilitated by the release of enzymes called proteases, which degrade extracellular matrix and facilitate the metastatic spread of cancer. TNF[alpha] and IL-1[beta] are potent cytokines that share the ability to stimulate angiogenesis, hence their possible significance in metastasis has been a focus of intense research. TNF[alpha] and IL-1[beta] have been shown to regulate the activity of proteases such as MMP's and serine protease. The aim of this study was to investigate the effect of TNF[alpha] and IL-1[beta] on cathepsin B and DPP IV activity and their protein levels in HRT 18, HT 29 cells and HUVEC's. Further experiments were conducted to assess the viability of the cells upon treatment with the cytokines. In addition the potency of inhibitors Mu-Phe-Hph-FMK, for cathepsin B enzyme, and Gly-Pro-Gly-Gly, for DPP IV enzyme were assayed in the three cell lines studied. Addition of TNF[alpha] and IL-1[beta] resulted in the reduction of intracellular cathepsin B and DPP IV activity and an increase in its extracellular activity in HRT 18 and HT 29 cells, suggesting that the cytokines induced the release of the enzymes or may have inactivated intracellular enzyme while activating the latent extracellular enzyme. However, in HUVECs, both the cytokines led to an increase in intracellular as well as extracellular cathepsin B activity, possibly by activating the latent form of enzyme present within and outside the cell. With respect to DPP IV, there was an increased intracellular and extracellular activity with TNF[alpha], but with IL-1[beta], an increase in intracellular activity and a decrease in extracellular activity were observed, suggesting involvement of a different mechanism for the exopeptidase enzyme in HUVECs. The two Cytokines had a cytotoxic/cytostatic effect on all three cell lines, with prominent reduction in cell viability of HUVECs. In conclusion the varied response of intracellular and extracellular activity and protein levels of cathepsin B and DPP IV, in different cell lines suggests that TNF[alpha] and IL-1[beta] may act as important modulators of proteases in the process of angiogenesis in cancer and normal endothelial cells. Thus understanding the pleiotropic nature of these cytokines will further broaden the knowledge of involvement of these cytokines in cancer progression/cancer regression.

Accurate detection and segmentation of intracranial aneurysms plays an important role in diagnosing and reducing the incidence of subarachnoid haemorrhage (SAH) which is associated with high rates of morbidity and mortality. This research proposes a computer aided detection (CAD) and segmentation (CAS) of intracranial aneurysm in computer tomography angiography (CTA). The efficiency of the CAD/CAS system is boosted by pre-processing the input image with non-linear diffusion to smooth the CTA data while preserving the edges. A 3D region growing-based approach is used to extract the cerebral arteries followed by entropy-based search space reduction to retain the volume of the circle of Willis (CoW) and the proximal cerebral arteries where nearly all intracranial aneurysms are located, whilst eliminating the extracranial and very distal intracranial circulation. Because cerebral aneurysms vary in size we regard the problem of cerebral aneurysm detection as an intrinsically multi-scale problem and employ a multi-scale approach to all detection analysis. Shape index analysis is employed to determine potential aneurysmal regions (PARs). Hessian analysis and gradient vector field analysis which reveal 3D local shape information are used to further characterise the initial PARs. False positive reduction is then performed based on the analysis of the shape characterisations of the PARs. A ranking score is defined based on the outcomes of the shape analysis to rank the likelihood of PARs. The system allows user to navigate through the ranked PARs and select a candidate aneurysm for further analysis (CAS). The boundary of the selected aneurysm and its parent artery is delineated by using a 3D conditional morphology-based region growing approach. The output is presented to the user to be assessed for the aneurysm orientation relative to the parent vessel. A semi-automatic process is applied to detach the aneurysm from its parent artery. To have a fine segmentation of aneurysm which can be used for characterization of the aneurysm, a 3D geodesic active contour implemented in a level set framework is applied. The volume of the separated aneurysm is quantified as a typical characterization ofthe aneurysm. The system has been validated on a clinical dataset of 62 CT A scans with average 274 slices per scan (involving 17,028 CT slices) containing 70 aneurysms. Sizes of aneurysms vary between 3-16mm. 42 CTA scans have been used as a training dataset for parameter selection and 20 CTA scans have been used as a test dataset. The sensitivity of the systems for the CAD component is 97% with the average false positive of 2.24 per dataset (0.008 per slice). CAS performance was evaluated by dual visual judgment of an expert neuroradiologist and neurosurgeon. The detection and segmentation performance indicate the approach has potential in clinical applications.

This thesis addresses the theory of Socio-Technical Systems (STS) within the context of Information Systems (IS), a complicated field combining Information Technology and social shaping impacts. IS have been changing our society for some decades. From Office Automation (OA) to E-Commerce and E-government, IS are creating a new era of Mobilisation. Different industries have all been adopting Information Technology to enhance their business, from enterprises to public sectors. All these changes bring dramatic impacts for organisational behaviour and people's living, which need to be studied. According to academic literature, health informatics, being one of the important and complex fields in IS, started to employ mobile technical systems to improve healthcare service delivery for citizens at the start of the new Millennium. Comparing with other theoretical models in IS, the author argues that the Socio-Technical approach can explain comprehensively the new changes to organisations and society. Following the theories of STS, these case studies were decided by the researchers as field work in Chinese Community Healthcare Service Centres, where there are various mobile services for the citizens. Through multiple case studies, the author found that Leader Emphasis is one new social element in the field of the IS, while Participation, as another social element is essential to the context of this research project. These two social shaping elements, combining together within a model of STS, provide new decision making process, which is vital to a successful development of Mobile Health Information Systems (MHIS). The model has affected organisational behaviour, organisational structure, culture and society, following the usage of Mobile IS. Based on the result of the field work and the relevant literature of E-govemment, this research also concludes that M-govemment can be the transformation of E-govemment, as public service can be delivered efficiently by Mobile IS. A developing model is presented in this thesis.

This thesis tells the tale of a special group of healthcare 'customer service' workers called the Patient Advice Liaison Service (PALS). It looks at how their job is designed and explores the impact this has, on their wellbeing by using a mixed-method research design which includes one quantitative and one qualitative study. The starting occupational level study is based on quantitative data from 138 participants using a questionnaire that measures global wellbeing, job satisfaction and psychosocial work conditions. A high incidence of strain is reported, statistically higher than that of other customer service employees and more comparable to social workers. Psychosocial conditions at work are revealed to be dire and in need of urgent action; and yet, the same group of workers report satisfaction with their job. To further unwrap the complex lived experience of PALS workers, an individual level study was conducted. Interpretative phenomenological analysis was undertaken with nine participants. Four emergent themes affirm that when it comes to their job, others just don't really get it, especially the extent of their emotion work. Changing the NHS is compared to changing a super tanker's direction and participants confess to having had a breaking point. Nevertheless, PALS staff declare that this is a vocation and I wanna do it. Reflexive interpretations suggest that some customer service employees actually engage in rather complex work that is not easily captured by the broad 'customer service' label. For individuals engaged in this type of relational work emotion work was found to be both a source of distress and motivation. Comparisons between these healthcare workers and other public sector relational workers are made and the new discourse of expertise services is proposed. Theoretical and policy implications are discussed.