Background: Effective delivery of dental services must be based on reliable information regarding the prevalence and severity of disease in the target population. Evaluation of the various factors known to influence the severity and progression of disease is essential for health policy makers to promote oral health resources and address oral health needs. Objective: The overall aim of this research is to describe the situation of dental caries and investigate the associations of level of oral health knowledge, teeth irregularity, BMI and other life style variables (TV viewing, internet use, passive smoking and dietary habits) with dental caries, including the impact of socio-demographic factors amongst school children in Qatar. Materials and methods: A cross-sectional study was conducted in Qatar from October 2011 to March 2012. A total of 2,113 children aged 12-14 years were randomly selected from 16 schools from different areas. Clinical examination was conducted by three calibrated examiners using World Health Organization criteria for diagnosing dental caries. Teeth irregularity was determined clinically according to a method described by Björk et al (1964). A pre-tested and structured questionnaire was used to assess oral health knowledge and life style data. Data analyses were performed. Results: The mean decayed, missing and filled teeth index values was 4.62 (±3.2), 4.79 (±3.5), and 5.5 (±3.7), respectively, for the 12, 13 and 14 year old children. The caries prevalence was 85%. The mandibular incisors and canines were least likely to be affected by dental caries, while maxillary and mandibular molars were the most frequently attacked by dental caries. Of the total sample, only one quarter reported a high level of oral health knowledge. There were more incidences of teeth crowding (44.1%) than teeth spacing (9.5%). The overall prevalence of underweight, overweight, and obesity was 5%, 10%, and 5% respectively. Almost half of the children spent > two hours watching television and 46% spent > two hours using internet. Approximately 35.8% of children had exposure to passive smoking. Concerning dietary habits, 99.4% of children consumed sugar containing snacks in between meals. Approximately 65% consumed sugar containing snacks within one hour of bed time. Almost 49.1% skipped eating breakfast regularly and 22.7% skipped eating lunch regularly. Around 83.8% consumed diary snacks in between meals. Overall, 74.2% drank tea in-between meals and 80.1% chewed gum in-between meals. All variables were affected by socio-demographic factors, but significant differences were found in female children in that they were more at risk to dental caries than male children. Also, children who resided in semi-urban areas were more at risk to dental caries than children who resided in urban areas. The occurrence of dental caries is significantly associated with the level of oral health knowledge, teeth irregularity, and other life style variables. Conclusion: The need to reduce sedentary behaviors and to promote a more active and healthy lifestyle is becoming increasingly essential in Qatar. Implementation of a community-based preventive oral health programs on a healthy diet and practices of adequate oral hygiene should be promoted in schools through integration into the school curriculum and services to combat the growing problem of dental caries.

Antimicrobial resistance is an international public health problem and is associated with increased morbidity, mortality, and healthcare costs. Antibiotic consumption, particularly indiscriminate use of these agents, is recognised as a major cause of resistance. Clinical guidelines recommend that in otherwise healthy individuals, antibiotics should not be used in the management of acute dental conditions, in the absence of spreading infection and systemic upset. Instead, a surgical intervention should be the first-line treatment for such problems. This thesis describes the use of antibiotics for acute dental conditions in primary care in the UK, and explores factors that influence prescribing for dental problems using a mixed methods approach.

Globally malaria still remains the most important parasitic disease of public health interest. In the recent past, most endemic countries have deployed and scaled up both preventive and curative interventions to reduce malaria transmission and, ideally, eliminate it. This has lead to global reductions in both mortality and incidence of malaria. These declines have been attributed to the reinvigoration of the global malaria control agenda by the explicit ambition of achieving elimination, which has lead to an increase in funding for national control programmes to increase coverage of preventive interventions, field compatible diagnostic tools for confirming parasite infection, and increased access to effective treatment. As a result of declines in malaria transmission, the focal nature of malaria transmission has become much more evident and has lead to consideration of surveillance as a key intervention for malaria control/elimination in its own right. Surveillance systems have been well established in most formal health facilities but the incorporation of these systems at community level and operationalised by community health workers (CHWs) still remains limited. Additionally, these few examples of CHW-implemented surveillance systems have been typically only reporting indicators of malaria infection burden, without capturing indicators of intervention availability, deployment, coverage and utilisation, thus representing a missed opportunity for routine monitoring and evaluation of impact of interventions in “real time” to inform program planning and implementation. The study was established as part of a multi-country study under the Malaria Transmission Consortium Project whose primary objective was to develop and evaluate new or improved methods for measuring malaria transmission. Thus the overall goal of this study was to demonstrate how malaria transmission, and impact of interventions, could be routinely measured through a novel longitudinal community based surveillance system (CBSS) operationalised by modestly paid CHWs. The CBSS included both passive and active surveillance activities using field – compatible test kits for in situ parasitological detection of malaria infections, based on which confirmed cases were treated with anti-malarial drugs, coupled with a detailed questionnaire on access and use of malaria control interventions and population characteristics. Passive surveillance was achieved conventionally whenever community members self-reported to the CHWs and active surveillance was achieved through monthly active visits to all households in their catchment populations to offer testing and treatment. In addition to recording detailed details of each patient contact in a paper patient register, weekly summaries of selected data elements were submitted by the CHWs using a mobile phone platform via short messaging system (SMS). The detailed reference data recorded in the patient register was then used to monitor malaria infection dynamics in the study population, evaluate the impact of preventative measures, such as indoor residual spraying (IRS) and long-lasting insecticidal nets (LLINs) and validate the electronic summaries submitted via SMS. Overall, the CBSS did not routinely capture all malaria infections in the study population and was insufficient to eliminate the human parasite reservoir. This was primarily due to limited study participant participation with the monthly active testing and treatment offered by the CHWs. However, the CBSS clearly demonstrated the incremental and residual impact to supplementation of pyrethroid-treated LLINs with non - pyrethroid insecticides applied by IRS in areas where the dominant malaria vector is highly resistant to pyrethroids. The adequacy of the SMS reports submitted by the CHWs confirms the great potential of mobile phone technology for facilitating and improving the effectiveness of community based reporting. Despite its limitations, the CBSS successfully provided programmatically relevant information regarding malaria infection dynamics across the large study area at a very affordable cost. The CHWs demonstrated their ability to not only provide treatment services but also adequately report their findings both electronically and on paper. CHWs are primarily tasked with providing routine health services at community level but clearly also have a valuable auxiliary role to play in “real time” surveillance of malaria, and most probably a range of other diseases. If the full potential of CHWs as agents of health surveillance can be realized, control programme progress can be measured through spatial and temporal mapping of transmission with greater sensitivity and at finer scales than is possible with health facilities alone, to enable improved, better-informed program planning, resource allocation and implementation.

Plasmodium falciparum is responsible for most malaria-related morbidity and mortality, mostly affecting young children, non-immune adults and pregnant women. A characteristic feature of the pathogenesis of infection caused by P. falciparum is the cytoadherence of infected erythrocytes to the endothelial cells lining the microvessels of host organs. This phenomenon, termed ''sequestration'', mainly results from the adhesive interactions between P. falciparum erythrocyte membrane protein-1 (PfEMP1) proteins on the surface of infected erythrocytes and various host endothelial receptors such intercellular adhesion molecule 1 (ICAM-1), which is hypothesised to have a role in cerebral malaria. PfEMP1 molecules consist of several Duffy binding-like (DBL) and cysteine rich interdomain region (CIDR) domains that have different cytoadhesive functions. The second class of DBL domains, DBLβ, has been associated with adhesion to ICAM-1 receptors. In the present study, we selected four recombinant PfEMP1ICAM-1-DBLβ domains for mouse immunisations. Thirteen monoclonal (mAbs) and polyclonal antibodies (pAbs) were raised to three recombinant domains (DBL13, DBL31 and DBL41). All mouse mAbs and pAbs comprised IgM antibodies that recognised homologous and heterologous DBLβ domains. Most mAbs and pAbs labelled the surface of erythrocytes infected by P. falciparum isolates, with an IgM labelling capacity ranging from 10.1% to 67.6% of total IEs. Mouse antibodies showed similar patterns of reactivity with ICAM-1-binding and non-binding isolates, and reacted with a parasite isolate from a different genome (3D7). Surprisingly, we detected a remarkable reduction in IE population after incubation with mouse mAbs and pAbs, and this was mainly observed with antibodies that strongly labelled the surface of IEs. We demonstrated that this haemolysis was resulted from an immunological interaction between mouse IgMs and a parasite-derived component on the surface of live IEs. Antibodies raised to DBL41 were the most effective in all assays. Of these, three antibodies (pAb B5, mAb B4, mAb G6) and an anti-DBL31 mAb (E7) significantly blocked IE adhesion to purified proteins (ICAM-1 and CD36) under static and flow conditions. These antibodies also blocked parasite adhesion to HUVEC under conditions of blood flow. In a separate work, we characterised the immune response of eight semi-immune serum samples obtained from female adults living in Kilifi County, Kenya. Our results indicated that semi-immune sera specifically recognised five recombinant DBLβICAM-1 domains and a VAR2CSA DBL domain, and recognised the surface of erythrocytes infected by diverse parasite isolates with variable levels of reactivity. Some sera, particularly JA225 and JA235, significantly inhibited IE adhesion to ICAM-1 under both static and flow conditions. To our knowledge, this is the first study to examine the use of PfEMP1ICAM-1-DBLβ domains for the development of mouse mAbs and pAbs that recognise homologous and heterologous parasite isolates and block IE adhesion. However, further work is required to identify the surface ligand(s) involved in interaction with mouse IgM and to investigate the mechanisms of IgM-mediated IE lysis.

Giardiasis, cause by the parasitic protozoan Giardia duodenalis, is one of the most common infectious gastrointestinal diseases in humans worldwide. However, its true population burden and epidemiology and in particular its zoonotic transmission potential are still poorly understood. Furthermore, G. duodenalis is not a uniform parasite but a complex of seven genetic assemblages or cryptic species (named A to G) that infect humans and a variety of domesticated and wild animals, and that can only be distinguished using molecular genotyping methods. Although there is some evidence that the two Giardia assemblages infecting humans (namely A and B) may differ in their virulence and major transmission routes, data are still scarce. In the UK, several studies suggested that giardiasis is considerably under-diagnosed and a few data are available on the genetic diversity of the parasite causing infection and disease in this country. We investigated the burden, clinical outcomes, risk factors and molecular diversity of giardiasis in North West England using both a descriptive and analytical approach. In Chapter 2, we analysed the self-reported clinical and exposure data collected over four years from clinical cases of giardiasis in Central Lancashire, as part of an enhanced surveillance program on the illness. The resulting average disease rate of 22.5 cases/100,000 population was high when compared to the available national figures. Giardiasis was particularly abundant in adults in their 30s and children under five, and the disease rate in males was significantly higher than in females. Furthermore, the clinical picture of the cases confirmed the high morbidity associated with this infection particularly in terms of the length of illness and severity of symptoms. Only 32% of the cases reported foreign travel during the exposure window. The results suggested the presence of a hidden burden of disease in adults and males, and indicated that local transmission of Giardia can be more common than expected. In Chapter 3, we performed a case-control study to determine the significant risk factors for symptomatic giardiasis in North West England, by recruiting clinical cases of Giardia and age and sex matched controls from Central and East Lancashire and Greater Manchester. The multivariable logistic regression analysis done on 118 cases and 226 controls revealed that overall travelling abroad (particularly to developing countries) was an important risk factor for the illness (OR 9.59). Following the exclusion of participants that reported foreign travel, four risk factors were significant for the acquisition of giardiasis: going to a swimming pool (OR 2.67), changing nappies (OR 3.38), suffering irritable bowel syndrome (OR 3.66) and drinking un-boiled water from the tap (OR 8.17). The results indicated the important role of swimming pools and contact with children in nappies for the transmission of the parasite. In Chapter 4, whole faecal DNA was extracted from the faecal samples of the cases part of the surveillance and case-control studies and the Giardia assemblages and sub-assemblages causing infection were determined using PCR amplification and DNA sequencing of up to four parasite genes (beta-giardin, glutamate dehydrogenase, triose-phosphate isomerase and small-subunit ribosomal RNA). The majority of infections (64%) were caused by assemblage B, followed by assemblage A (33%), whereas mixed-assemblage infections were rare (3%). The majority of the assemblage A isolates belonged to the sub-assemblage AII and showed completed identity with previously described isolates, and six multi-locus genotypes were identified. The level of genetic sub-structuring as revealed by phylogenetic analysis was significantly higher in assemblage B isolates compared with A isolates: a higher proportion of novel assemblage B sequences was detected compared to what was observed in assemblage A isolates. A high number of assemblage B sequences showed heterogeneous nucleotide positions that prevented the unambiguous assignment to a specific sub-assemblage. Up to 17 different assemblage B multi-locus genotypes were found. The molecular genotyping results showed that Giardia assemblage B was responsible for the majority of the clinical infections and confirmed the occurrence of a high diversity of parasite multi-locus genotypes. In Chapter 5, we integrated the epidemiological and the molecular data generated by the enhanced surveillance and case-control studies and we studied the clinico-epidemiological differences between cases infected with Giardia assemblage A or B. Our results showed a difference in the age prevalence between the two assemblages, with assemblage A being more common in older cases. Cases infected with assemblage B reported a series of symptoms more frequently than cases infected with assemblage A, as well as reporting a longer illness. Although the exposure profile of the cases largely overlapped between the two assemblages, two different types of exposures were reported more frequently in the two groups of cases: keeping a dog in assemblage A cases and the presence in the household of children and children at nursery in assemblage B cases. The results suggested that assemblage A could have a major zoonotic reservoir, whereas assemblage B could be transmitted more commonly via the human-to-human route.

Background: The health sector has ‘duty of care’ to provide comprehensive health services to survivors of violence, to act as a referral point, to collect and document evidence, to report data on violence and to engage in preventive services. In Malawi, 48% of women experience some form of intimate partner violence (IPV) and a significant number report conditions requiring health care services, although few actually report to health services, which are in turn limited in scope and availability. Understanding how health care providers, relevant stakeholders and IPV survivors perceive the role of health care services in IPV is necessary to promote the development of context-relevant and sustainable health care interventions. Aim: To understand the health service responses to IPV in Malawi from a wide range of perspectives Objectives: i) to critically analyze written legislation, policy and strategy documents in relation to IPV and the health sector in Malawi; ii) to describe the perceptions and experiences of IPV and of health sector responses among survivors of violence, community members, health care workers and other key stakeholders in Malawi; iii) to estimate the extent of intimate partner and sexual violence from a health service uptake perspective using proxy determinants at one referral hospital in Malawi iv) To explore the policy implications of the study findings for the health sector responses in Malawi. Methods: In 2011, a multi-method situation analysis was conducted in three areas of Blantyre district, with additional data collected in Mangochi and Lilongwe districts. Seventeen relevant national documents were analyzed. A total of 10 focus group discussions (FGDs), 2 small groups and 14 individual interviews (IIs) were conducted with health care providers; 18 FGDs and one small group discussion were conducted with male and female, urban and rural community members; 12 in-depth interviews (IDIs) with survivors; 26 key informant interviews (KIIs) with donor agencies, GBV service providers, religious institutions; police officers and other stakeholders were conducted. A review of 3,567 register records for the month of January 2011 was done in Queen Elizabeth Central Hospital and police records on violence cases in Blantyre for the same month were reviewed. Qualitative data was analyzed using the ‘framework’ approach, assisted by NVIVO 9 software. Hospital records were analyzed using Epi Info™. Feminist approaches and the ecological framework for analysis of violence informed data analysis and interpretation. A range of quality assurance measures were undertaken and data were triangulated across all methods: policy analysis, interviews and records reviews. Findings: A review of legislation and policy combined with qualitative stakeholder interviews revealed conflicts, gaps and lack of awareness of the available documents that undermined coordinated health sector responses. Survivors, community members and health care workers revealed that IPV is perceived as a massive, though under-recognised problem. IPV in its various forms was seen as widespread and normalised, except perhaps in the perceived severe forms (such as femicide and child rape). IPV, though considered as shameful, was not necessarily a very private matter with involvement of neighbours, families, friends and significant others. Various factors at individual, interpersonal, society and institutional levels were described as affecting under-reporting, access to services and responses from sources of support. The review of registered data confirmed that IPV is generally underreported in health services and that relying on trauma as a proxy for IPV against women would prove difficult to implement. This multi-method approach highlighted the importance of diagnostic identification and the difficulties of universal screening. The actual role of health services in IPV seemed fuzzy from the service user’s perspectives and narrowly confined to the bio-medical model or acute model of health service provision. However, both potential service users and health care providers were optimistic about new developments such as ‘One Stop Centres’ and about the potential role of health services, particularly those linked to HIV programmes. They suggested these be provided as a continuum from prevention to rehabilitation. Conclusions: This study found a range of laws and policies that define and promote action to prevent IPV in Malawi. These have had some positive influences on both community norms and health sector responses. However, ineffective promotion has limited their effectiveness. In addition there are gaps and inconsistencies that reduce their potential in guiding the health sector response to IPV. The study explored stakeholders’ perceptions of IPV, the health sector response and the factors shaping it. This revealed a complex web of interconnected socio-economic, cultural, political and institutional factors. Perceptions of violence are culturally normative and related to gender roles and expectations. The inclusion of male voices on IPV against men, and using emic definitions of violence revealed conflicts between women’s and men’s interpretations of IPV, particularly with regard to sexual violence and the transgression of gender and marital roles. The specific socio-economic and cultural context strongly favours a conflict resolution model of responding to violence, which raises questions about the mandate and the potential roles of the health sector. Most stakeholders perceive IPV as a significant problem and recognise multiple impacts on health. However there is a clear disconnect between the magnitude of the problem and the health sector response. Nevertheless, the health sector is well placed to play a leadership role and has some resources, such as HIV Testing and Counselling staff and curricula to offer in a multi-sectoral response. Proxy determinants as reflected in the health service registers proved to be inadequate due to poor reporting and recording, and under-reporting to health services. Under-reporting was influenced by a range of inter-connected barriers to formal help-seeking, including normative attitudes and ineffective responses by both informal and formal sources of support. However, knowledge was generated about the challenges to recording and reporting IPV in this setting. The study findings suggested a number of key opportunities for improving the health sector response to IPV in Malawi that may be appropriate in this specific context and considered their potential sustainability.

Introduction In this thesis, analytical approaches for the design and evaluation of cluster randomised trials are presented and reviewed. In particular, statistical power/sample size issues relating to the design of cluster randomised trials for which only a limited number of clusters are available are assessed using a series of simulation studies. The use of computer simulation methods made it possible to investigate how well cluster randomised trials with limited numbers of clusters available can be optimised both in terms of statistical power and also the accuracy of parameter estimates. The study design conditions performing best in the simulation studies were then applied to a community intervention study involving informal healthcare providers: the 'Triage Plus integrated tuberculosis (TB) and human immuno-deficiency virus (HIV) community intervention project in Lilongwe rural, Malawi'. Aims and objectives The general aims of this dissertation were to: 1. investigate if it is possible to improve the analytical approach to the evaluation of cluster-randomised trials where the complexity of the intervention demands a small number of clusters and in which the primary outcome measure is a count of events occurring in a specified time interval; 2. investigate the effectiveness of engaging informal healthcare providers in integrated TB and HIV community intervention in treatment initiation rates and testing access rates, a cluster randomised trial was conducted in Malawi for which only a limited number of clusters were available to the researchers. The specific objectives were: 1. to review cluster randomised trials and the statistical methods used in the assessment of the effectiveness of the intervention in this type of trial when the primary outcome measure is a count of events occurring in a specified time interval; 2. to assess the statistical efficiencies of different design conditions in terms of statistical power and the accuracy of parameter estimates when determining the effectiveness of complex interventions with a limited number of clusters in this situation; iii 3. to identify the circumstances under which each of the statistical methods would be most robust in detecting significant intervention effects or providing accurate estimates of intervention effects; 4. to apply these statistical approaches to the data collected in the cluster randomised clinical trial of community based interventions for TB and HIV (the 'Triage Plus' study); 5. to assess the effect of involving non-paid informal healthcare providers in integrated TB and HIV community interventions aimed at improving testing and treatment initiation rates for these two diseases. Methods Two research approaches were used in this dissertation: 1. Simulation studies were used to investigate statistical efficiencies in terms of statistical power and accuracy in parameter estimation under different study design conditions for cluster randomised trials in which the primary outcome measure is a count of the number of events occurring during a specified period of time. 2. These statistical approaches were then applied to obtain robust estimates of the effect of the test intervention using the data collected during the “Triage Plus” study. The Triage Plus intervention, implemented in rural areas of Lilongwe, involved informal healthcare providers in an integrated TB and HIV community intervention. This intervention specifically involved empowering the informal healthcare providers in disease recognition, sputum specimen collection, referral of presumptive TB cases, and conducting community TB and HIV awareness meetings. Results The simulation studies showed that statistical efficiency and power both varied considerably under the different design conditions investigated. Non-coverage rates within the nominal value of 5% and negligible biases in the estimated fixed effects parameters (regression coefficients) were observed for all scenarios investigated including the (minimal) 3 cluster per arm design. However, it was discovered that, in order to achieve adequate power in low incidence disease conditions such as TB treatment initiation rates, more repeated measurement times were required to achieve adequate power of 80% with a true effect size of 20% or lower (for example, 12 measurement times were needed to achieve adequate power in this situation in a 3 cluster per arm design when the ICC was 0.00154). With an ICC of 0.081 iv at least 9 clusters were needed to achieve adequate statistical power of ≥80% with an effect size of 20% with 6 and 12 measurement time points respectively for high and low incidence disease conditions. For an effect size of 40%, at least 3 clusters per arm were needed to achieve adequate power with 4 repeated measurement times in low incidence diseases and 3 measurement times for high incidence diseases. For ICCs of 0.321 and above, no adequate statistical power was achieved with an effect size of ≤40% in both high and low disease incidence conditions. In the analysis of the TB services access data from the Triage plus study, the intervention significantly increased the number of presumptive TB cases accessing testing sites by 15.2% (p=0.003) in the first 12 months of the intervention; however, this was followed by a statistically non-significant reduction of 18.3% (p=0.224) when the intervention was rolled-out into the control clusters. Overall, the intervention was associated with a non-significant increase in TB treatment initiation rates of 18% (p=0.112). In the analysis of HIV services access rates, antiretroviral therapy (ART) initiation rates increased significantly by 34.7% (p=0.048) in the intervention clusters in the first 12 months of intervention, and the ART initiation rates were similar after rolling-out the intervention to the control clusters. Overall, the intervention was associated with a 61% increase in HIV testing uptake rates (p<0.001). Conclusion: To achieve adequate statistical power and improved precision in parameter estimation in cluster randomised trials with a count outcome measure, with the ICC of 0.00154 the simulation results suggested that a minimum of 3 clusters per arm is required with at least 12 measurement times for the estimation of an effect size of 20% (or higher) in low incidence disease situations. However, for high incidence outcomes, a minimum of 3 clusters per arm with 3 or more measurement times may be adequate to achieve a statistical power of at least 80%. For an ICC of 0.081, at least 3 clusters per arm were needed to achieve adequate power if the effect size was 40% after 4 repeated measurement times in low incidence diseases and 3 measurement times for high incidence diseases. With ICCs of 0.321 and above, no adequate statistical power was achieved with an effect size of ≤40% in both high and low disease incidence conditions. For the TB and HIV interventions in the “Triage Plus” study, engaging informal health care providers was clearly effective in improving TB and HIV testing uptake as well as ART v initiation. This reinforces the need for community participation in integrated TB and HIV interventions to combat the two diseases. However, for these providers to be effective in promoting TB treatment initiation, the number of sites offering TB testing and treatment initiation in rural areas should be increased to make them more accessible to the population.

Modern healthcare has been shifting from a traditional fragmented disease-centred delivery approach towards a more integrated Patient-Centred (PC) one to support comorbidities, when the patient suffers from more than one condition or disease. In PC delivery the patient is at the heart of its services which are tailored to meet an individual’s needs holistically. Enabling PC care requires the flow of medical information with the patient between different healthcare providers supporting the patient’s treatment plan, and sharing of information across healthcare organisations so that the Care Team (CT) can seamlessly access relevant medical information held in different information systems. In many countries this PC movement is taking an evolutionary approach that involves Legacy Information Systems (LIS) as they are the backbone of the healthcare organisation’s information. However, this collaboration reveals weaknesses in LIS in this role, as they may block a CT from accessing information, as they cannot comply with the information security policies for shared information that is needed in this collaborative environment to support PC. This is mainly because each of these LIS was designed as an autonomous discrete information system that enforces an organisation-driven information security policy protecting only local information resources through an Access Control (AC) model. This creates a single local point-of-control, limited by the system’s physical perimeter, to meet local information sharing and security contexts. This means PC adoption may require incorporation of multiple autonomous discrete information systems which presents four challenges – inconsistent policies, perimeter-bounded AC models, multiple points-of-controls, and heterogeneous LIS. First, such collaborative environments lack collaboration-driven information security policies that best meet the protection needs in the collaboration sharing and security contexts. Second, they deploy incompatible AC models that are not perimeter-transparent, and thus, unable to stretch across the discrete information systems to cover the whole collaborative environment. Third, these environments do not deploy a single obvious point-of-control with authority for policy enforcement. Finally, they need to access heterogeneous LIS that are not compatible with each other, and thus, it is essential that solutions can be integrated and coupled with these LIS to facilitate the utilisation of information stored in these systems. Current solutions addressing this situation fall short of meeting these challenges in establishing secure collaborative environments with LIS because they lack a comprehensive information security approach to meet the information sharing and security contexts driven by the collaboration. This research introduces a roadmap towards achieving a Secure Collaborative Environment (SCE) in collaborative environments using LIS from diverse organisations that addresses the above challenges, and meets the collaboration information sharing and security contexts without interrupting the local contexts of these LIS. An empirical study is used to determine how to create an SCE in modern healthcare which addresses the problems raised by incorporating LIS. This meets the collaborative information sharing context by creating an information layer that manages the information flow between healthcare providers based on treatment points. It also meets the information security context in the treatment pathways by controlling access to information in each treatment point using a Patient-Centred Access Control (PCAC) model. This model creates a PC-driven information security policy at the collaboration level that meets the overall care goal, enforces this balance in a neutral security domain with a single authority point-of-control that stretches across organisations anywhere within the collaboration environment, while retaining the local medical information security of shared information among the CT. Using domain analysis, observations, and interviews, the PC-driven balance of information security in cancer care, threats in LIS currently used in cancer care to attain that balance, and eight information security controls are identified. These controls manage information through an information layer and control access to the information through the novel PCAC model needed by these systems to attain that balance and address the problem. Using Workflow Technology (WfT), a prototype system implementing these controls to achieve a Secure Healthcare collaborative Environment (SHarE) has been fully studied, developed, and assessed. SHarE constructs an independent information layer that is based on treatment and lies on top of the interface of the currently used LISs to formalise and manage a unique treatment journey, while the PCAC model enforces access rules as the patient progresses along their treatment journey. This layer is designed as a loosely coupled wrapper based system with LIS to embrace the local organisation-centred access controls without interruption and sustain the balance of information security. Finally, using interviews, SHarE was assessed based on three criteria: usefulness and acceptance, setup and integration, and information governance. Results show that all interviewees agree that currently information does not always flow with the patient as they go along their treatment journey and nine different causes for this were suggested. All interviewees with no exception agreed that SHarE addresses this problem and helps the information flow with the patient between healthcare providers, and that it would be possible for SHarE to be adopted by a CT in cancer care. Over half the interviewees agreed that it is an easy to use system, useful, and helps locate information. The results also show there is an opportunity for SHarE to be integrated with CaNISC as some interviewees thought it is a much simpler system. However, multiple patient identifiers for a patient, as each system can have its own identifier, is predicted to be the biggest integration challenge. Results also show that SHarE and its controls attain the right balance of information security defined by the Caldicott Guardian and comply with the six Principles of the Caldicott Guardian. Although the assessment of SHarE highlighted a number of challenges and limitations that may hinder its adoption and integration if not carefully considered in the future, this proposal allowed the achievement of creating an SCE required to adopt PC care and attain the security balance necessary to support PC care systems.

In 2014, the UK Government announced they were, 'going all out for shale gas,' as part of the UKs need to change the energy landscape to focus on security of supply, economic benefits, (reduction of imports), the need to cut carbon emissions and further establish renewable sources. Subsequent licencing to explore for Shale Gas resulted in significant publicised protests concerning environmental issues. Published literature in the form of Case Studies and completed Health Impact Assessments, of which there is a paucity, tend to support these concerns. However, clearly absent from this literature, are the Social Health and Well-Being Impacts (Social Determinants of Health) associated with Hydraulic Fracturing. Data was gathered using an on-line questionnaire which was open for six weeks. The questionnaire included both qualitative and quantitative methods of data collection. Ninety four respondents completed the questionnaire providing over seven hundred pieces of information and comments. Thematic analysis was used to analyse the data sets. The results of this analysis indicate that the threat to the quality of life, environmental concerns and a lack of confidence in the governance of the decision-making process as key factors in the perceptions of the participants. The complexities of these themes were then visually described using causal loop modelling techniques. The research concludes that the public have a very negative and mistrustful perception of Government, Statutory Bodies and the Oil and Gas Industry. Frequently cited social impacts include, stress, anxiety, loss of control and negative impacts on communities including environmental pollution. The implications of this research are that authorities and relevant bodies need to pay far more attention to people and community needs when granting and considering planning consent and licences.

Cognitive impairment is a major cause of disability for a large number of working-age adults living with chronic psychiatric and neurological conditions. Although well recognised in schizophrenia spectrum disorders and in neurological diseases such as multiple sclerosis (MS), cognitive impairment has historically received less attention in mood disorders. The relative prevalence of cognitive impairment in bipolar disorder (BD) and major depression compared with other conditions has not been clearly established, and the risk factors that drive cognitive variation within and across conditions are not well understood. The primary focus of this thesis was on BD, and the objectives were: (1) to investigate the prevalence of cognitive impairment in BD, compared with major depression, schizophrenia, MS and Parkinson’s disease (PD); and (2) to develop causal models to quantify and explain variation in cognitive function in BD and in other conditions. The methods encompassed a systematic literature review, a prevalence study using cross-sectional data from the UK Biobank cohort, and a series of multivariable analyses of UK Biobank data using graphical methods, regression- and matching-based estimation, and mediation models. The systematic review indicated that between 5% and 58% of adults with euthymic BD showed cognitive impairment. Prevalence was lower in the mania/BD group identified within the UK Biobank cohort, at around 7-10%, which was similar to rates seen in the MS and PD groups within the cohort. When causal models of cognitive performance in the mania/BD group took account of multiple potential confounders, performance on a short-term visuospatial memory test showed a small but reliable decrement. Mediation models provided evidence of indirect negative effects on cognitive performance via psychotropic medication, but not via cardiometabolic disease. A similar pattern of results was seen in the major depression group, though with smaller effect sizes. This thesis emphasises the importance of cognitive function as a fundamental phenotype in psychiatric and epidemiological research. There is scope to build on this work in future follow-up waves in UK Biobank, as well as in other UK and international cohort studies and through linkage with routine healthcare data.