• Expression of sigma receptors in human cancer cell lines and effects of novel sigma-2 ligands on their proliferation

      Abbas, Haider (2018)
      Sigma receptors originally thought to be an opioid receptor is now categorized as a distinct class of receptor. There are two main subtypes, the sigma-1 receptor and an uncharacterised binding site, named the sigma-2 binding site. The presence of the sigma-2 binding site shows high correlation with proliferation of cells and is associated with cancer. I have categorized sigma-1 and sigma-2 binding sites in 11 human tumour cell lines. I have demonstrated that tumour cell lines from a range of tissues express both sigma-1 and sigma-2 binding sites. One exception is the MCF7 breast cancer cell line, which lacks sigma-1 receptors. I show that the quantitation of sigma-2 binding sites using the “masking” protocols are flawed, significantly overestimating levels of sigma-2 binding sites. I propose novel protocols to determine levels of sigma-1 receptors and sigma-2 binding sites in cell lines and tissue. Using radioligand binding assays in MCF7 cells, I have characterised novel sigma-2 ligands. These ligands are simple ammonium salts containing a single nitrogen atom. They are simpler than the previously recognised pharmacophore for the sigma-2 site. I have shown that these simple ammonium salts show graded affinity for the sigma-2 binding site. The highest affinity ligands were dihexylammonium (pKi 7.58) and dioctylammonium (pKi 7.9). I have used these ammonium salts and previously characterised ligands to determine sigma-2 binding site biology. I have shown that the biological activity of these drugs is related neither to their hydrophobicity nor their ability to effect calcium signalling in cells. I propose that the Hill slope of binding is inversely related to the efficacy of a ligand to inhibit metabolic activity of cancer cells. Furthermore, I offer an explanation as to why concentrations of sigma-2 ligands far higher than their determined binding affinities are required to inhibit metabolic activity.
    • Evaluation of Bacterial Polymers as Protective Agents for Sensitive Probiotic Bacteria

      Adebayo, Olajumoke O. (2018)
      Probiotics are live microorganisms which when administered in adequate amounts confer one or more health benefits on the host. Different processing conditions, the acidic condition of the stomach and exposure to hydrolytic enzymes affect the viability and efficacy of probiotic organisms. This study investigated the protective effects of two biopolymers poly-gamma-glutamic acid (γ-PGA) and bacterial cellulose (BC) on probiotics during freeze drying and during exposure to simulated intestinal juices and bile salts. The antibacterial property of Bifidobacterium strains was also investigated against four pathogenic bacteria. γ-PGA, a naturally occurring biopolymer was produced by two bacteria (Bacillus subtilis ATCC 15245 and B. licheniformis ATCC 9945a) in GS and E media, γ-PGA yields of about 14.11g/l were achieved in shake flasks and molecular weight of up to 1620 k Da was recorded, γ-PGA production was scaled up in a fermenter with B. subtilis using GS medium. BC, an edible biopolymer was produced by Gluconacetobacter xylinus ATCC 23770 in HS medium and a modified HS (MHS) medium. A yield of about 1.37g/l was recorded and BC production with MHS medium was used for probiotic application. B. longum NCIMB 8809 B. breve NCIMB 8807 and B. animalis NCIMB 702716 showed the best antimicrobial properties against the investigated pathogens. Survival of Bifidobacterium strains was improved when protected with powdered BC (PBC) although γ-PGA offered better protection than PBC. Viability of B. longum NCIMB 8809, B. breve NCIMB 8807 and B. animalis NCIMB 702716 in simulated gastric juice (SGJ) and simulated intestinal juice with bile salts was improved when protected with 5% γ-PGA and 5% γ-PGA+PBC with a reduction of <1 Log CFU/ml while a reduction of ≤2 Log CFU/ml was recorded in PBC protected cells. Protecting Bifidobacterium strains with γ-PGA, PBC or a novel γ-PGA + PBC combination is a promising method to deliver probiotic bacteria to the target site in order to confer their health benefits on the host.
    • ‘Soldier-Diplomat: a reassessment of Sir Henry Wilson’s influence on British Strategy in the last 18 months of the Great War’

      Spencer, John (2018)
      Sir Henry Wilson remains one of the most controversial British Army generals of the Great War. A colourful character in life, he attracted admirers and detractors in equal measure; in death, his reputation was ruined by a biography based on his personal diaries. The Wilson of the historiography is, at best, a politician rather than a soldier, at worst an ambitious Francophile intriguer. This thesis looks beyond this accepted characterisation, reassessing his role in the formation of British and Allied strategy in the final months of the war. Wilson attained influence, and subsequently power, when Lloyd George consulted him after failing to persuade Britain’s leading generals to change their strategic focus. The thesis re-examines Wilson’s policy critique, which led to the creation of the Supreme War Council, and negated plans for a major Allied offensive on the Western Front in 1918. This thesis aims to shine new light on Wilson’s work on the Council, with an analysis of its policy recommendations. The research will also explore the manpower crisis, the key issue for the entente in this period, and Wilson’s contribution to the establishment of Allied unity of command. The diplomatic skills Wilson deployed to defuse serious strains between the entente powers will be examined, with particular reference to his time as Chief of the Imperial General Staff. His contribution to the debate on Britain’s post-war imperial grand strategy will also be evaluated. The thesis will refute the long-established onedimensional view of Wilson and suggest that he played a more influential role in British strategic development than has hitherto been acknowledged.
    • ‘Doing the Portfolio’ – Pre-registration training for biomedical scientists and developing the capable practitioner

      Smith, Sara (2018)
      Integration of work-placements into undergraduate degrees is now established on awards linked to professional registration in healthcare. Pre-registration training forms the basis for development of capability and entry onto a professional register. This enquiry explores how key stakeholders on a programme leading to registration as a Biomedical Scientist (BMS) position themselves in their role and the subsequent impact of this upon the development of the capable BMS. It draws upon current knowledge of work-based pedagogy and utilises a constructivist grounded theory (CGT) approach to explore the perceptions and experiences of individuals and groups to develop an interpretative portrayal and deeper understanding of the implementation of pre-registration training in one region of England. Data gathering and analysis was divided into two stages. The first employed analysis of professional documents to provide an insight into current discourses around BMS training. This provided initial developing categories and directed the creation of a questionnaire. Questionnaire responses confirmed the relevance of the developing categories and a summary of responses provided an ‘ice-breaker’ to guide stage two of data gathering. This stage employed focus groups and interviews to enable a greater understanding of how individuals make sense of their experiences. Initial, focused and theoretical coding allowed synthesis and conceptualisation of the data gathered and presented direction for the enquiry. The findings expose the challenges of integrating professional registration training into an academic programme of study. Three theoretical categories were identified: Role conflict, Expectations and Ownership. Conceptualising the interactions and intersections of these categories enabled the recognition of ‘Doing the portfolio’ as a way of describing and conceptualising the stakeholders positioning within the current programme. The registration portfolio has become an objective reductionist measure of learning, reflecting the positivist typology of practice in this profession. This provides a theoretical explanation as to how the programme is delivered and why there is a need to rethink conceptualisation of the role of the programme in supporting pre-registration training and the development of the capable BMS. To ensure that BMS students are supported to develop not only technical skills but also professional capability there is a need for a paradigm shift from a positivist episteme to one that embraces both the positivist and socio-cultural paradigms, viewing them as complementary and parallel. The novel research approach used in this enquiry has generated rich insights into how stakeholders interact with the pressures of internal and external influences and the impact this has upon behaviours and strategies adopted. The theoretical understanding proposed, which recognises the tensions emerging from a positivist typology of practice, has a range of implications for practice and for the development of practitioner capability through pre-registration training and beyond.
    • Growing pains to growing shame and beyond: a reflexive dyadic on stigmatised identity

      Pursehouse, Lucy (2018)
      Stigma surrounding mental health is a significant concern within the UK. Education, is considered an important aspect in attempts to address negative attitudes. This thesis opens a dyadic space in which I explore personal stigma stories relating to mental health. In addition, to consider how these connect to my doctoral journey and practice. Furthermore, how such phenomenological expression contributes pedagogically to a contemporary policy imperative; one aimed at tackling mental health stigma. The research design is methodologically grounded in the autoethnographical method and I have developed both an ‘analytical’ and ‘evocative’ approach. Five central themes emerged from my personal stigma stories and data analysis, ‘dissimilitude’, ‘disconnection’, ‘bifurcation’, ‘assimilation’ and ‘transformation’. Theoretically rich stories were then crafted, that re-presented these themes to provide further sense-making. A perspective transformative process is tightly woven within and throughout, capturing a critical pedagogic frame of reference for the inquiry. The study adds to the existing body of literature, by contributing personal narratives in the form of stories and poetry, which may be used within my anti-stigma education. The methodological processes revealed the importance of autoethnography and its analytic reflexive potency for moving beyond a stigmatised identity. Insights gathered, enabled the development of a Model of Learning on stigma, Right Stigma Capabilities, a learning tool to be utilised in practice, and the theoretical conceptualisation of a ‘Pseudo-Medicalised Identity’. Robust mechanisms for education, continuing professional development and mentoring are required, across a multi-disciplinary health and social care context. Further research is required on the lived experience of stigma, and the generative processes involved in liberation from this complex social phenomenon.
    • Institutional and Social Factors Influencing Informal Sector Activity in Sub-Saharan Africa: A Nigerian Case Study

      Joshua Adike, Abinotam (2018)
      The extant entrepreneurship literature is replete with competing narratives about the concept of informal sector (IS). Also, IS’ potential as a source of income and the behavioural tendencies of operators in the sector remain highly contested but under-researched. In particular, not much is known about the incentives and the motivations for engaging in informal economic activity from the perspective of Sub-Saharan African (SSA) context where a significant proportion of all economic activities are informal. Thus, the lack of conceptual clarity and consensus about the underlying factors driving individuals into informal economic activity constitutes a major knowledge gap. To fill this gap, this study seeks to clarify the domain of IS from a SSA viewpoint, and through this paves the way for a more holistic understanding of the behavioural tendencies and motivations of IS operators in SSA. Specifically relying on the institutional, social exclusion, and personality trait theoretical frameworks, the study demonstrates how a combination of separate yet related phenomena of personality traits, institutional factors, and more importantly, situational factors that manifest as perceptions of social exclusion serve as the incentives and the motivations to engage in informal economic activity in SSA. To achieve its goal, qualitative primary data obtained through thirty-eight semi-structured interviews were transcribed verbatim and analysed using Nvivo. Firstly, the study found that institutional ambiguity, institutional delinquency, institutional passivity, and institutional incongruence are sources of voids in Nigeria's institutional framework that influence an individual to enter the IS. Secondly, social exclusion regarding lack of access to requirements such as finance and formal education to start and sustainably operate a business influences people to enter into the IS. Lastly, the findings indicate that personality traits’ influence regarding the decision to engage in informal economic activities is dependent on individual circumstances. These are valuable contributions to the stock of knowledge about the IS. Particularly, the identification and categorisation of four specific institutional voids and partitioning of the sources of exclusion; the finding that in adverse economic circumstances personality traits could influence potential opportunity-entrepreneurs to start-up in the IS; the finding about the role of trade associations; and the new understanding about the collaborative dimension of corruption in the context of IS practice, represent a significant contribution of this study. These contributions are valuable not just in terms of creating new windows of research opportunities, but also for evidence-based policy relating to the IS that is appropriately targeted at relevant groups. This is in addition to facilitating collaborations for business support, enlightenment, improved business practice, and inclusive growth.
    • Policy and Politics matter: The shaping of contemporary social work in times of neoliberalism.

      Simpson, Graeme (2018)
      The commentary draws on a range of work to demonstrate the argument that policy and politics are of central importance in shaping social work in England. I outline the development of my practice wisdom and then examine the contested nature of social work knowledge. Drawing on my practice with people who were poor and marginalised, I came to believe that social work must have a commitment to equality and social justice and that to achieve this social work must engage with policy and politics. My outputs begin by examining the connection between my practice wisdom and the dialectical nature of social work’s enduring tensions, located in a work that underlines the importance of sociology. A further four outputs focus upon aspects of social policy, notably key elements in the rise of neo-liberalism in contemporary social work in a text that argues explicitly that social workers need to develop a politically engaged practice. My other outputs illustrate the impact of politics, neoliberalism and its attendant policies in the early 21st century, gathering evidence from three broad areas. First, the nature of globalisation is examined focusing upon the movement of social workers and ‘cross-national’ social work. Second, there is an explicit exploration of social work under neoliberalism, drawing on the case of Children’s services and learning disability. Third, I examine ‘policy practice’ and the concept of ‘choice’. I argue that social work has always had a concern with politics and policy but that in more recent years this has declined and has been overtaken by a focus upon individualism. My core theoretical themes are the dialectic and an examination of hegemonic structures which impact on social work. I explore the continuing importance of my work in relation to contemporary social work, showing that policies and politics matter more than ever. I conclude by arguing that, as social work is under political attack from the current Government, the ‘radical tradition’ needs to be kept alive.
    • Volunteering in the higher education curriculum: the politics of policy, practice and participation

      Green, Pat (2018)
      This study explores the extent to which government policies for higher education impact upon the ways in which higher education institutions (HEIs) implement these and the students themselves experience their studies. The focus is accredited volunteering in higher education. A case study approach has been undertaken to scrutinise the impact of policy directives on several stakeholders within one post-1992 HEI, the University of Wrottesley (a pseudonym). The methodological approach is qualitative. Semi-structured interviews were carried out with senior university staff and Students Union personnel, and a detailed on-line survey was conducted with three cohorts of students undertaking the Volunteering in the Curriculum (ViC) programme. What emerges is the extent to which the dominant discourse of ‘employability’ is foregrounded in government policy directives, and the pressures thus placed on the university management of Wrottesley to respond effectively to first destination scores (DHLE). ‘Employability’ in this sense is understood as a graduate student obtaining employment, rather than a broader sense of good learning which embraces both learning (cognitive, theoretical and practical) and employability (Knight & Yorke, 2004). The findings expose the ways in which volunteering has been drawn into the dominant discourse of ‘employability’, yet what emerges from the student survey of their participation in the ViC programme is a broader, more nuanced learning experience which draws on both experiential and theoretical learning that encompasses academic studies, personal development, social action and graduate employment. The evidence validates the theoretical and pedagogic practice of ViC whereby students experience holistic learning. Universities such as Wrottesley are missing an opportunity in not embracing wider objectives of initiatives such as ViC which enable enhancement of graduate employability and also learning gain with the development of well rounded critical citizens and institutional permeability between community and the academy.
    • Through the Lens: Using Auto-Driven Photo-Elicitation to Capture the Development of Career Aspirations of Business Management and Fine Art Students

      Turley, Helene (2018)
      The uniqueness of this study is primarily in the application of a visual research methodology to generate knowledge and understanding in an area that is often associated with quantitative research. Careers and employment research typically focuses on statistical information which can provide general information but does not give an in-depth understanding of the area under study. Visual research can give an in-depth understanding; in addition to giving access to a different kind of knowledge, supported by Harper (2002) who proposes “that images can evoke deeper elements of human consciousness than words alone.” I explore the various ways in which students perceive and develop different career aspiration including what motivates and what might inhibit students’ development of their career aspirations. This understanding will enhance my professional practice and encourage the Careers and Employment department within the University to adapt their service and give students the relevant tools and information to prepare them for employment. A visual research methodology is utilised as this fits comfortably with my background in art and gives the in-depth knowledge I require for my research (see Clark-Ibáñez, 2004; Collier (1957); Collier and Collier, 1986; Cousin, 2009; Guillemin and Drew, 2010; Harper, 2002; Harris and Guillemin, 2012 and O’Brien, 2013 for further information on the benefits of using a visual research methodology). Auto-driven photo-elicitation (ADPE) is used with six fine art and six business management students. These students often have less career direction and tend to struggle to secure graduate level positions (Swani, 2016); in addition, the two subject areas were chosen because they are a contrast in terms of how their curriculum is delivered. Using visual research to inform careers and employment is unique and through sharing my research and research experience I want to initiate a shift in how careers and employment research is approached in the future. In addition to the uniqueness of using a visual research methodology in careers and employment my findings indicate there are five orientations business management and fine art students’ use when developing their career aspirations: a strong sense of direction, intrinsic and extrinsic motivations, weak planning and dreams. This research discusses the five orientations and the factors that might contribute to a rich learning environment for career building. Subject and professional identity are discussed in relation to identity formation and career building. Four main sources of identity formation are identified: identity through being (transition from study to profession), identity through self-discovery, identity through belonging (concerning the informal and cultural aspects of community life), and identity through peripheral participation (activities that are akin to peripheral participation in a professional community). This research establishes there is a relationship between the development and building of identity and self-efficacy through belonging, professional experience and working alongside mentors when developing strategies to develop career aspirations.
    • Self evaluation variables and social media

      Harrad, Rachel (2018)
      People are motivated to self evaluate and undertake this in their interactions with others. Interactions with others are increasingly taking place online, including via social networking websites, which can contain several differences to face to face interaction. This thesis examined how specific self-evaluation factors (self-esteem, social comparison tendency and self-concept clarity) affect various behaviours on and psychological outcomes of engaging with social media sites, including Facebook. Self-esteem predicted positive mood during Facebook use, whilst one’s relationship with the site (i.e. how emotionally connected to the site one is – or ‘Facebook intensity’) predicted engagement with activities interpreted as indicative of a ‘fear-of-missing-out’ (e.g. finding out what friends were up to). High scorers in performance and appearance self-esteem reported a positive mood shift after profile editing whilst low scoring counterparts reported the reverse. Those who compared to others frequently experienced a negative mood shift after viewing the Facebook newsfeed possibly reflecting the cognitive effort associated with social comparison. Self-esteem predicted use of positive emotions in status updates whilst number of Facebook friends was negatively predicted by self-concept clarity and positively by social comparison tendency. Participants textually described both their actual and ideal self enabling consideration of the implications for self-presentation attempts in certain online environments. Low self-esteem individuals decreased their use of anxious language when idealising the self whilst those with low self-concept clarity increased their use of positive emotions. The discrepant word count between actual and ideal selves suggested that the actual self appeared more easily articulated, most 4 pronounced amongst those who infrequently compared themselves to others. When others rated these self descriptions it appeared high scorers in self-esteem and self-concept clarity and those who compared frequently to others were generally most positively received. It appears that whilst those with unclear self-concepts and low self-esteem can present a more positive and less anxious idealised self than actual self, the overall thesis findings appear to support the rich-get-richer hypothesis (Valkenburg, Schouten, & Peter, 2005) with high scorers on these self-evaluation factors garnering the most benefits from social media. Whilst those who compare frequently may be adversely impacted by viewing the Facebook newsfeed, idealisation of self attributes appears to benefit these individuals in terms of positivity of impressions formed by others. Findings suggest that social media engagement may hold advantages and disadvantages for users dependent on the type of activity engaged with and the individual differences variables of the user.
    • Metformin as a potential therapy for malignant astrocytoma

      Eagles, Lawrence (2018)
      Background Glioblastoma Multiforme (GBM) is the most commonly occurring tumour of the central nervous system (CNS). Currently GBM is considered an incurable malignancy with patients experiencing abysmal life expectancies. Lack of progress in the discovery of novel treatments has led to the repurposing of existing licenced medication as a possible alternative option. Metformin is from the biguanide family of drugs and is the most common medication used in the treatment of type 2 diabetes. Clinical studies have reported that, in type 2 diabetic patients, metformin might reduce cancer incidence and severity. Currently, metformin is being assessed in clinical trials as a treatment for a range of cancer types including GBM. The antineoplastic mechanisms utilized by metformin and other biguanides have not been fully elucidated. Methods The effects of metformin were evaluated, alone and in combination with other agents, on a panel of GBM cell cultures. Functional analysis of metformin mechanism of action was assessed through measurement of apoptosis, depolarisation of the mitochondria membrane, caspase pathway activation, cell cycle progression and the expression levels of micoRNAs. Results Analysis of fourteen GBM cell cultures showed a cytotoxic response to metformin that was significantly linked to the P53 status (p=0.0024). In combination drug testing, one of the four drugs showed a synergistic pairing with metformin. The kinase inhibitor sorafenib, showed synergism (CI ≤ 1) in eight GBM cell cultures. Flow cytometry of metformin treated GBM cells showed no significant increase (p>0.005) in apoptotic cell populations. Caspase 3/7 levels showed no significant increase post metformin treatment (p>0.005). Metformin caused depolarisation of the mitochondrial membrane in six GBM cell cultures. Four microRNAs were shown to have expression levels changes post-metformin treatment. Upregulation of expression was identified in miR-140, miR-192, let-7c. Downregulation was identified in miR-222. Conclusions Metformin was shown to have cytotoxic effect on a GBM cell cultures and has potential as GBM therapeutic agent and possible treatment synergy with sorafenib. The significance of P53 status to metformin sensitivity may suggest that its use should be directed to a sub-set of GBM patients. Mechanism for cell death by metformin was shown not to rely on apoptotic pathways but caspase 3/7 independent depolarization of mitochondrial cell membranes and cell cycle arrest. Investigations into autophagy may help to further define the pathways metformin is utilising to promote cell death. The impact of metformin on the expression profile of miR-222, miR-192 and let-7c is in line with clinical studies of other cancer types. This shows possible insight into the cancer independent actions of metformin. The interplay recorded between glucose availability and cell death indicates a possible key factor in the utilisation of metformin as a therapeutic agent. This finding may warrant the addition of dietary control regimes in clinical trials to maximise metformin efficacy. This work highlights the strong potential for biguanides in the development of new drug treatments and in expanding our knowledge of cancer metabolism.
    • Developing a model for assessing the effect of physical indoor environment quality on teachers’ performance in Saudi education buildings

      Alzahrani, Hamdan M. (2018)
      The nature and quality of the built learning environment affect occupants’ comfort, wellbeing and performance. Within the broad range of studies of the physical indoor environment reported in the literature, there are several which have focused on the effects of these environmental conditions on the comfort and physical health of students and teachers, while the main consideration in others is the organizational health of the school. The parameters, which are measured often concern the state and condition of the physical environment. Categories of building features, which appear to influence comfort, health and wellbeing, include thermal sensation, acoustics, lighting, air quality, classroom equipment, learning resources and other aspects of the teachers’ workspace. Those components of the physical of indoor environment, which are considered to most strongly affect occupants’ comfort, wellbeing and performance, are subject to sets of standards. The aim of this study is to elucidate the association between the indoor environmental quality (IEQ) of educational buildings and teachers’ performance. Following a comprehensive review of the literature on the effects of IEQ on teachers’ comfort, wellbeing and performance, a case study was conducted in which physical measurements were made of a range of indoor environmental variables in the classrooms of a technical college in Saudi Arabia, during lessons. At the same time, the teachers of those classes were asked to complete a questionnaire designed to investigate the quality of the indoor environment and explore teacher performance. An artificial neural network was then used to create an assessment model in order to test the hypothesis that the quality of the indoor physical environment in educational buildings is related to teacher performance and to predict future data. This research makes both academic and practical contributions to the study of the relationship between IEQ and teachers’ performance. The findings of this research will be used as a primary knowledge resource for future researches and to identify initial IEQ parameters and tools for further in-depth studies. In practical terms, it offers standards to help designers to consider the importance of IEQ and its impact on building users.
    • Drought, drought mitigation in Yobe State, Nigeria

      Hassan Gana, Abdullahi (2018)
      Drought is regarded as a natural phenomenon and its impacts accumulate slowly over a long period. It is considered to be insufficient precipitation that leads to water scarcity, as triggered by meteorological parameters, such as temperature, precipitation and humidity. However, drought mitigation has mostly been reactive, but this has been challenged by extreme events globally. Many countries and regions around the world have made efforts in mitigating drought impacts, including Nigeria. This research produced frameworks for drought amelioration and management as a planning tool for Yobe State, Nigeria. Mixed methods were employed to investigate the effects of drought; 1,040 questionnaires were administered to farmers in three regions of Yobe State (South, North and East). Some 721 were returned, representing a 69.3% return rate. Drought is pronounced in the State and has been recent over the years; it has also affected many people, with losses of ~70-80% of their harvests and livestock. Drought coping strategies have also caused environmental degradation in Yobe State. Farmers over-harvest their farms, practise deforestation and over-exploit wild animals. Several efforts to mitigate the impacts of drought by the Nigerian Government have failed, thus this research adopts a bottom-top approach to mitigate drought impacts in Yobe State. Focus Group Discussions (FGD) were also conducted at government and community levels to gather farmers’ and government officials’ opinions on their drought experience and suggestions for mitigation measures. Farmers believed that rainfall is their main problem and officials pointed that there are no proper drought mitigation plans in Yobe State. Four validated drought mitigation and management frameworks were developed for Yobe State. The frameworks were evaluated pre-use through respondent validation. State officials and farmers believed that these frameworks will reduce the impacts of drought in Yobe State. The frameworks include social, economic, environmental impact mitigation and an Integrated Drought Mitigation and Management Framework. The proposed frameworks were designed and have advocates a paradigm shift, using both proactive and reactive measures. A new drought definition was proposed based on the findings of the study. The definition states that drought is the shortage of rainfall or water that affects people’s livelihood and the environment both directly and indirectly.
    • Physiochemical and drug release properties of liquisolid formulations in comparison to their physical mixture counterparts

      Bello, Hussaini (2018)
      Various techniques have been used for modifying the release properties of drugs over the past years. Techniques such as liquisolid technology have raised a lot of interest in many researchers which can be employed to enhance or sustain dissolution. Various liquisolid (LS) tablets of diltiazem containing Polysorbate 80 as a non-volatile solvent for sustained release were prepared. PolyoxTM is an attractive pharmaceutical polymer used in controlled release dosage forms mainly because of its insensitivity to the pH of the biological medium and ease of production. The aim of this study was to investigate the influence of several formulation factors i.e., the PolyoxTM grade at different molecular weight (MW), PolyoxTM particle size and ratio, the AEROSIL® grade, the use of diluent, polymer type and the drug type as well as their interactions on drug release from LS formulation in comparison to their physical mixture (PM). The result showed that PolyoxTM MW was a key determining step in achieving sustained release, with the higher MW of PolyoxTM resulting in a more delayed release profile. The delayed DTZ release could be related to the rate and extend of hydrogel formation on the tablet surface. The P–CMRs and net–CMRs of both LS and PM formulation powders also showed increasing trends with increasing the MW of PolyoxTM. The release of DTZ from both LS and conventional tablets showed mostly decreasing trends with increasing PolyoxTM concentration and decreasing PolyoxTM particle size distribution. This could be attributed to the formation of stronger and thicker gel layers on the tablet surfaces in the case of higher concentrations of PolyoxTM. The results also showed LS tablets to produce slower release of drug than their PM counterparts, regardless of PolyoxTM particle size. The release profile of the DTZ from both LS tablets and their counterpart PM tablets showed decreasing trends with increasing the surface area of hydrophilic AEROSIL® (from 65 m2/g to 225 m2/g). This could be due to the higher tensile strength (TS) of the tablets containing AEROSIL® particles with higher surface area compared to those prepared using AEROSIL® particles having lower surface areas. Also, the result showed that comparing the different diluents showed that hydrogenated vegetable oil (HVO) provided the slowest release pattern of DTZ across diluents used in both the LS compacts and PM tablets. This could be attributed to hydrophobicity imparted by HVO to matrix system when in contact with aqueous medium it takes a longer time to penetrate into the tablet. Drug release from LS tablets was affected by the polymer type. The release was in the order: Eudragit® RL < Eudragit® RS < Hypromellose < PolyoxTM < Psyllium. Hydrophilic Psyllium provided a slowest DTZ release across the different polymers used in the preparation of both the LS and PM compacts. The incorporation of Psyllium into PolyoxTM further elicited a decrease in drug release rate from individual polymer matrices. This was ascribed to the reduced entrance of aqueous media into the matrix due to the presence of the stronger viscose gel within the two hydrophilic matrices compared to individual Psyllium and PolyoxTM. The ratio between PolyoxTM and Psyllium has critically influenced diltiazem release profile. The results showed that matrices containing (Psyllium:PolyoxTM) at 1:1 ratio can slow down the drug release more than the matrices compacts containing 1:3 and 3:1 (Psyllium:PolyoxTM) ratio. The results also suggest that the ii combination of PolyoxTM and Psyllium at 1:1 ratio showed robust dissolution against pH and rotational speed and therefore indicates an appropriate sustained-release profile. The dissolution rate of PolyoxTM:Psyllium from different pure drugs showed a decreasing trend with an increase in their solubility. The solid state analysis studied in this work confirms the presence of a fraction of the drug mass in a solubilised state within polysorbate 80 in LS powders. Regardless of all variables used in this study, LS formulations showed slower drug release than their PM counterparts. In conclusion, the mechanical properties of LS formulation are poor in comparison to their counterpart PM. Therefore, further work is required to improve the hardness of LS tablet comprehensively.
    • An interpretative phenomenological analysis investigation into the subjective experience of being diagnosed with dyslexia in adulthood

      Chinenye, Njoku (2018)
      A large number of adults remain unaware that the difficulties they encounter may be related to dyslexia. Diagnosing dyslexia in adulthood may provide the means to reasonable accommodation to help in areas of difficulties but may also impact on the individual’s sense of self. To date, little research attention has been paid to idiographic experiences of adulthood diagnosis of dyslexia and subsequent adjustment issues related to the diagnosis. The aim of this study is to develop indepth understandings on subjective conceptualisations, meaning making and adjustments issues to the experience of adulthood diagnosis of dyslexia. Semistructured interviews were conducted with seven individuals diagnosed with dyslexia in adulthood to explore this experience. Interviews were analysed using Interpretative Phenomenological Analysis (IPA) from which five superordinate themes emerged: ‘De-constructing the past to make sense of the present’, ‘Roller coaster of emotions to dyslexia and diagnosis’, ‘Stigma, stereotypes and stereotypical attitudes towards dyslexics’, ‘The Paradox of self-disclosure’ and ‘Support following dyslexia diagnosis’. These superordinate themes, with their associated subordinate themes, are expanded into a narrative account of adults’ experiences. The findings revealed that adulthood diagnosis of dyslexia entailed a range of experiential processes that culminated to ‘identity transformation’. These findings can help in deepening understandings of the effect of adult dyslexia diagnosis on identity; contribute to existing practices in counselling psychology, educational institutions and employment agencies providing supportive services for individuals with dyslexia.
    • The Role of a Deglycating Enzyme ‘Fructosamine-3-Kinase’ in Diabetes and COPD.

      Alderawi, Amr Saleh (2017-10-31)
      Recent statistics show that approximately 415 million people worldwide have diabetes. Glycated haemoglobin (HbA1c) measurements were introduced many years ago as the gold standard tool for detecting and monitoring treatment as well as making management decisions for diabetic patients. Glycated haemoglobins are formed by the non-enzymatic glycation of haemoglobin molecules. This non-enzymatic glycation process has been strongly related to pathogenesis of chronic complications associated to diabetes. It was suggested that this glycation process may be moderated by an enzymatic deglycation process thought to involve a deglycating enzyme known as Fructosamine-3-kinase (FN3K), an enzyme that deglycates the glycated haemoglobin in erythrocytes and other glycated proteins in other tissues. FN3K acts through phosphorylation of fructosamines on the third carbon of their sugar moiety, making them unstable and consequently causing them to detach from the protein. The degree of deglycation is thought to depend on the activity of the FN3K enzyme. Moreover, variation in the activity of FN3K between individuals is hypothesised to lead to apparent differences in glycated haemoglobin levels: some individuals have high rates of deglycation so that they tend to have lower average glycaemia than actually the case, while others with low rates of deglycation appear to have higher than actual glycaemia (known as the glycation gap, G-gap). The G-gap has been reported to be associated with alteration of diabetic complications risk. The G-gap reflects the discrepancy between average glycaemia as determined from glycated haemoglobin (measured as HbA1c) and that from the determination of fructosamine. The positive G-gap is defined as a higher level of glycation of proteins than expected whereas a negative G-gap means a lower level of glycation than expected. To explore the role of FN3K in diabetes and other associated morbidities, we decided to divide our research into 3 studies. Each study was categorised according to the type and the source of samples involved. The first study explored the correlation between FN3K activity and protein level with G-gap data; it involved 148 diabetic patients who were recruited at New Cross Hospital, Wolverhampton, selected as having a consistent positive G-gap > +0.5 and a consistent negative G-gap > -0.5 over a minimum of 2 estimations. Age, gender, race and BMI were collected from patients in this study. Blood samples were also 3 collected to measure FN3K activity, protein levels, and markers of CVD in relation to G-gap. The second study involved 23 AECOPD patients who were recruited from St George’s Hospital (London) and were treated with either metformin or a placebo. Serum samples were collected from these patients for a larger study: we assayed those 23 serum samples for FN3K protein levels to explore any possible correlation between FN3K with metformin therapy in COPD patients. The third study utilised 36 human peripheral lung samples from healthy individuals, asymptomatic smokers and stable COPD patients (GOLD 2) who were recruited at The Section of Respiratory Medicine, University Hospital of Ferrara, Italy. Those samples were assessed for FN3K expression by means of immunohistochemistry to explore the difference in FN3K activity between those three categories. It was found that the intracellular activity and protein expression of the FN3K enzyme in diabetic patients negatively correlated with the values of G-gaps where FN3K activity was high in patients with negative G-gap. FN3K serum protein levels were shown to be enhanced with metformin administration in COPD diabetic patients, suggesting a protective role for FN3K enzyme against protein damaged caused by the non-enzymatic glycation of proteins. Therefore, patients with positive G-gap have lower FN3K activity than those with negative G-gap, and in turn they are more susceptible to diabetes related complications. Our data also indicate that metformin has a beneficial effect in reducing damage caused by carbonyl stress from cigarette smoking in COPD patients by the action of FN3K. Our research has demonstrated that FN3K contributes to the protein repair system which protects against damage caused by non-enzymatic glycation. The high activity for the FN3K enzyme was associated with low levels of AGEs and low carbonyl stress levels in observed among patients with diabetes and COPD. In contrast, COPD patients tend to have low FN3K-mediated protection against protein damage in comparison to the normal population. These patients tend to be at risk for developing more complications, particularly CVD complications, than normal, healthy individuals. Treatment with metformin enhances FN3K action in COPD diabetic patients, possibly as a protective enzyme against the damaged caused by the non-enzymatic glycation.
    • TRADE BASED MONEY LAUNDERING: EXPLORING THE IMPLICATIONS FOR INTERNATIONAL BANKS

      NAHEEM, MOHAMMED AHMAD (2017-10-10)
      Written in response to a current gap in academic and industry based literature, this thesis was written on the topic of Trade Based Money Laundering (TBML) and risk assessment, within the banking context. Despite the increased use of TBML, most academic descriptions of money laundering have used the cash based model of placement and integration of large cash deposits acquired from criminal activity, which are then merged into legitimate pre-existing funds. However, there are a significant number of examples to show that cash transferred into goods and then shipped to other countries can be easier to move and less conspicuous or traceable than simple cash based deposits. One of the main challenges for detecting shipping based laundering techniques is that they involve a number of agencies sharing data and information, in order to catch the criminals. Simple banking checks may not always elicit the required information without verification from either customs or law enforcement agencies. The research sought to identify the current challenges and issues facing risk assessment professionals in the banking sector and to identify gaps in the current systems being used. The data collected included interviews and survey information taken from professionals working on AML risk assessment in banking and financial institutions from across the globe. In addition to the description of different money laundering schemes, much of the current academic discussion on money laundering in banking has focused on the regulation requirements for financial institutions to stop money laundering activity, but there has been little empirical guidance on how regulation can be adapted and implemented at the individual banking level. This research accessed a number of legal cases available in the public domain, which were analysed to see how and where some of the larger banks have failed to implement current anti-money laundering controls and to consider how this could impact on the detection of TBML activity. This research uses an Agency theory model to look at the pressures banks are under to manage client’s accounts efficiently, versus the requirements of outside regulation to undertake extensive checks on business transactions and accounts. Finally, the researcher proposed a simple risk matrix approach that developed the current thinking of client behaviour and transaction monitoring risk analysis associated with cash based laundering, to develop a four-point risk model that added geography and third party behaviour, to account for shipping and trade based laundering activity.
    • A NOVEL SELECTIVE INHIBITOR FOR PLASMA MEMBRANE CALCIUM ATPase 4 IMPROVES VEGF-MEDIATED ANGIOGENESIS

      Kurusamy, Sathishkumar (2017-10-02)
      Ischaemic cardiovascular diseases are the leading cause of death worldwide. Therapeutic angiogenesis provides a valuable tool to treat these conditions by stimulating the growth of new blood vessels in the ischaemic tissue. The pro-angiogenic factor VEGF is the most potent inducer of angiogenesis, and exogenous delivery of VEGF has been a key element of therapeutic strategies. Unfortunately, VEGF-based pro-angiogenic procedures have produced only limited patient benefit. Failure to restore efficient VEGF activity remains a major problem. VEGF-mediated activation of the calcineurin/NFAT signalling pathway has been identified as a crucial regulator of angiogenesis. Our laboratory has recently shown a novel role for the plasma membrane calcium ATPase 4 (PMCA4) protein as a negative regulator of VEGF-induced angiogenesis via interaction with calcineurin. The recent identification of aurintricarboxylic acid (ATA) as a selective inhibitor of PMCA4 prompted us to hypothesise that inhibition of PMCA4 with ATA should enhance VEGF-induced angiogenesis. Here, we show that treatment of endothelial cells with nanomolar concentrations of ATA notably enhances calcineurin/NFAT signalling by disrupting the PMCA4/calcineurin interaction. ATA mediated inhibition of PMCA4 results in a significant increase in endothelial cell motility and in vitro and in vivo blood vessel formation. Low concentrations of ATA do not have any deleterious effects on the viability of endothelial cells or zebrafish embryonic development. However, high ATA concentrations impaired endothelial cell viability, and were associated with toxicity in zebrafish embryos. This study highlights the potential of targeting PMCA4 to improve VEGF-based pro-angiogenic therapeutic strategies. This goal will require the development of refined versions of ATA without associated toxicity, or the identification of novel PMCA4 inhibitors.
    • Corporate Governance in the Banking and Finance Sector.

      CHUNG Chun Pong, Thomas. (2017-08)
      The focus of this thesis is an examination of certain weaknesses in the corporate governance at UK and US banks which constituted an underlying cause of the crisis. It considers the regulatory responses to these identified weaknesses and assesses to what extent these have led to improvements in corporate governance at banks. This research is based on an examination of all the failures at UK and US banks during and after the crisis, and of its related responses. In addition to UK and US responses, several solutions to the weaknesses identified at UK and US banks are addressed through EU legislation. The conclusions are that board effectiveness was low due to a lack of knowledge and of challenging of senior management; there was a culture placing growth and profit over risk management; and remuneration was structured leading to unacceptable risk taking resulting in scandals. It is concluded that the mechanisms to limit the impact of a failure of a bank on its stakeholders were inadequate. A case study of the financial crisis in US during the 1990s is undertaken to consider whether the US regulatory response offers lessons to UK regulators and legislators. The finding is that analysis of regulation and corporate governance at banks is problematic. There were similarities between the two financial crises, the organisation and culture of the UK and US banks is so different that different regulatory responses follow.
    • A study of architecture for art, design and visual media in the West Midlands from the 20th century onwards based on the perceptions of individuals

      Cooper, Carol (2017-05-04)
      The study investigates how museum and gallery buildings can be designed to give functional longevity and appeal. It considers this in terms of their design and relation to their surroundings and use in the context of changing social, cultural, political and economic factors. Post World War II the typological design and layout of these buildings was challenged; partly as a result of the influence of modernism and also as new modes of art production challenged the spaces and display modes. Financial instability and class perception have always been problematic and increased public expectations add to issues that need addressing. The study investigates how these factors have impacted on these buildings and if this has influenced their design and use. It considers the regional context of the West Midlands and also draws comparisons to other areas in England to investigate ways of addressing contemporary issues to achieve longevity of use. The study considers the historical influence of the typological developments. Examples from the West Midlands and investigation of the area’s historical background are used to identify if regional idiosyncrasies exist and if these influence a building’s longevity. This establishes their contemporary context and objectively reviews the resulting implications of appearance and function in relation to the social, cultural and economic issues that may be dominant within this region. A qualitative interview methodology and analysis is used to examine the views of a multidisciplinary group of museum and gallery users, capturing a snapshot in time of their views on the appearance, understanding and use of these buildings. This information is analysed and discussed in conjunction with the findings of the relevant literature. The comparison of the information researched raises regional and national issues associated to design and use of these buildings. Four key themes related to the longevity of use emerged; architectural design, location, economic viability and inclusivity.