RSS 1.0Theses and Dissertations
Recent Submissions
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Recalling trauma: the legacy of slavery and colonialism in contemporary black women’s fictionThis thesis examines key literary representations of black women’s historical trauma linked to colonialism and slavery. Through comparative readings of contemporary fiction by black women writers from two continents, I explore the intimate links between the historical traumas of colonialism and slavery and the identity of black women in novels by Toni Morrison, Chimamanda Ngozi Adichie, Edwidge Danticat, Tsitsi Dangarembga and Scholastique Mukasonga published between 2004 and 2014. The authors I consider represent literary historians engaging with traumatic pasts in order to rewrite and (re)present black women in a global present. From a postcolonial feminist and cultural trauma viewpoint, I reflect on the manifestations of slavery and colonial trauma on black women characters and explore the ways in which they navigate the historical limitations of collective trauma in their respective locales. My readings interrogate and demonstrate the possibility of a postcolonial feminist and decolonised trauma model that is specific to black women’s writing through a global, transcultural, and transnational outlook. This is a model which centres the experiences of black women from around the world as it is depicted in literature by black women. In addition to this, I examine the solidarities envisioned by the authors under investigation in this thesis in terms of a progressive decolonised trauma studies which encourages healing beyond borders for female descendants of former slaves and formerly colonised peoples. By uncovering the links between the remembering of traumatic events and the processes of healing as groups –– as opposed to the individualised Euro-American models articulated by pioneer theorists ––I situate my interrogation of a specific postcolonial feminist trauma theory as being crucial to my reading of my primary texts and argue that through this, we can uncover ways in which the fiction discussed here articulates and offers routes to communal healing from (initially through voicing) the previously unsaid traumas that are specific to the experience of black women in postcolonial settings. As its contribution to knowledge, this thesis introduces and utilises a decolonised trauma model which situates the black female historical perspective into specific focus and includes as well as studies postcolonial women’s fiction as part of a historical corpus. The thesis also demonstrates a closure of the gap between cultural texts written by American black women and other black women from around the world. Through a comparative analytical methodology and a theoretical framework which combines theories of cultural trauma, black and postcolonial feminisms, it locates black women’s trauma as a significant specific area in the fields of feminism, postcolonial trauma studies, comparative literature, world literatures in English, women’s studies, and studies in fiction.
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Necrolabour: A postqualitative contextualisation of contemporary work in respect to the philosophy of Georges BatailleThis thesis represents a reading, existential at its base, of the protean space of contemporary labour, under the lens of French philosopher Georges Bataille (1897–1962). A historical overview of the understanding of labour reveals the contemporary moment as positioned on the threshold of the Fourth Industrial Revolution and the Anthropocene. A moment, which in the context of this thesis, is best described in eschatological terms and is defined by the notion of permeability. The fading boundaries between labour, life, employment or unemployment, the distinction between product and producer, the empirical real and the virtual, all these ideas seem to merge into what can be described as the overloading of the Cartesian body/mind divide, introducing a host of unexplored ontologies and subjectivities. The thesis traces the movement towards a paradoxical post-work society, where nothing is classed as pure work and yet everything is a form of labour. This is labour that is immaterial, affective, and most importantly, post-human. The contemporary labourer—an embodied osmosis between the human and the machine—navigates through a ‘life-productive’, subordinated to the wage relations, opaquely managed by the spectral machine that is the algorithm. The work of Bataille, strongly engaged with historical concepts of work, sovereignty and existentialism, offers a rich commentary whose absence has been detrimental in regard to labour theory. An oversight whose importance becomes evident when juxtaposing the modern consideration of the human, the citizen, and the worker as interchangeable, with Bataille’s designation of work as the origin of the human animal. This thesis picks up the thread that the late Mark Fisher first unravelled regarding the omnipresence of capitalism and the lack of any alternative suggestion. The concept of necrolabour results from an interdisciplinary approach that goes beyond relating Bataille to a particular philosophical tradition, in favour of an applied reading of Bataille’s thought. Utilising a Postqualitative methodology, this thesis argues for an Acéphalic (in reference to the secret society of Acéphale Bataille founded), approach to labour and extends Achille Mbembe’s concept of Necropolitics from the purely political to the sphere of work. Acéphalic thought offers a radical yet pragmatic way to confront contemporary existence. Proposing a ‘within and against’ mode, our working lives—and by extension, the existential framing of ourselves—are to be encountered.
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An empirical evaluation of m-health service users’ behaviours: A case of BangladeshMobile health (m-health) services are revolutionising healthcare in the developing world by improving accessibility, affordability, and availability. Although these services are revolutionising healthcare in various ways, there are growing concerns regarding users' service quality perceptions and overall influence on satisfaction and usage behaviours. In developing countries, access to healthcare and low healthcare costs are insufficient if users lack confidence in healthcare service quality. Bangladesh's Directorate General of Health Services (DGHS) provides the only government-sponsored m-health service available to the entire population. DGHS's m-health service, available since 2009, is yet to be evaluated in terms of users' perceptions of the quality of service and its impact on satisfaction and usage. Hence, this study developed a conceptual model for evaluating the associations between overall DGHS m-health service quality, satisfaction, and usage behaviours. This study operationalised overall m-health service quality as a higher-order construct with three dimensions- platform quality, information quality, and outcome quality, and nine corresponding subdimensions-privacy, systems availability, systems reliability, systems efficiency, responsiveness, empathy, assurance, emotional benefit, and functional benefit. Moreover, researchers in various service domains, including- healthcare, marketing, environmental protection, and information systems, evaluated and confirmed the influence of social and personal norms on satisfaction and behavioural outcomes like- intention to use. Despite this, no research has been conducted to determine whether these normative components affect m-health users' service satisfaction and usage behaviours. As a result, this study included social and personal norms along with overall service quality into the conceptual model to assess the influence of these variables on users' satisfaction and m-health service usage behaviours. Data was collected from two districts in Bangladesh- Dhaka and Rajshahi, utilising the online survey approach. A total of 417 usable questionnaires were analysed using partial least squares structural equation modelling to investigate the relationships between the constructs in Warp PLS. The study confirms that all three dimensions of service quality and their corresponding subdimensions influence users' overall perceptions of DGHS m-health service quality. Moreover, overall DGHS m-health service quality has a significant direct association with satisfaction and an indirect association with usage behaviours through satisfaction. While social norms do not influence satisfaction and usage behaviours within the DGHS m-health context, personal norms directly influence users' satisfaction and indirectly influence usage behaviours through satisfaction. Theoretically, the study contributes by framing the influence of users' overall m-health service quality perceptions, social and personal norms on their actual usage behaviours rather than the intention to use. It also extends the existing knowledge by assessing and comparing m-health users' continuous and discontinuous behaviours. Methodologically this study confirms the usefulness of partial least squares structural equational modelling to analyse a complex model including a higher order construct (i.e., overall perceived service quality). Practically, the study demonstrates the importance of users' satisfaction in addition to service quality, as service quality only affects usage behaviours through satisfaction in the current study context. Additionally, knowing that personal norms significantly influence service satisfaction motivates providers of m-health services to strive to enhance users' personal norms toward m-health service to enhance service satisfaction and usage. Overall, the study will help enhance patient outcomes and m-health service usage.
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Registered nurses’ experiences of working with trainee nursing associates in acute hospital settings: a generic qualitative studyLaunching new roles in healthcare settings can be controversial; potentially threatening the status of existing professionals. The introduction of the Trainee/Nursing Associate (TNA/NA) role occurred in response to a governmental mandate to bridge the gap between unregulated generic healthcare support workers and Registered Nurses (RNs) in 2016. Nursing associates support RNs in the provision of quality patient care. Within a growing body of literature exploring the impact of the introduction of TNAs/NAs, there is a clear research gap addressing what it is like to work with TNAs, exclusively from the RN perspective. I adopted a Generic Qualitative Research Approach (GQRA) to explore RN experiences. This overarching GQRA approach provided a method of exploring the discipline of nursing. My study is aligned to the constructivist branch of interpretivism with a narrative inquiry lens. Phenomenology and hermeneutics are integral to my study design, focusing on the lived experience of participants. Purposive criterion sampling recruited five RN participants who took part in an individual face to face semi-structured interview during 2018. Reflexive Thematic Analysis generated five themes and seventeen subthemes. The five themes were, Apprehension, TNAs alleviate pressure and provide support, Conflict and tension, Professional accountability and Harmony and reciprocal learning. Findings revealed that RNs journeyed from an initial position of apprehension and uncertainty as they worked with TNAs, to a later position of accepting and welcoming TNAs to the role across a variety of acute clinical settings. An unexpected finding was the existence of conflict, tension, jealousy and animosity from healthcare support worker colleagues toward TNAs. The introduction of new healthcare support roles can be contentious. A myriad of dynamics impact on the acceptance and successful embedding of new roles into existing teams. The exclusive RN perspective within a generic qualitative research approach, with both a narrative inquiry and hermeneutic interpretative lens makes this study unique. My study is timely and adds to the developing body of knowledge where an in-depth understanding of the RN experience of working with TNAs and NAs is not evident. Various recommendations have been proposed for three different audiences: the nursing profession and nursing practice, workforce planners and managers, and educationalists in academic settings.
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The genetic interactions of PKHD1 and ATMIN in autosomal recessive polycystic kidney disease (ARPKD)The main gene associated with Autosomal Recessive Polycystic Kidney Disease (ARPKD) is PKHD1 which encodes a ciliary protein associated with planar cell polarity. In mice, mutations in the transcription factor Atmin can present with an ARPKD-like phenotype with kidney disease similar to an early manifestation of ARPKD. Like the mouse gene Pkhd1, mutations in Atmin are associated with altered WNT/PCP expression. Previous work has suggested that Atmin and Pkhd1 do not physically interact, but Atmin may modulate Pkhd1 expression. However, the mechanisms governing this relationship are unknown. ARPKD is a rare disorder typically associated with severe kidney and liver disease in children. The disease has considerable clinical and familial variability, but little is known regarding genotype-phenotype relationships. It has been proposed that genetic modifiers may influence disease severity. Next-generation sequencing (NGS) using ChIP-Seq and RNA-Seq techniques in mouse kidneys and intermedullary collecting duct (mIMCD3) cells identified new transcriptional targets of Atmin, which did not include Pkhd1 but included genes associated with cystic kidneys in animal models (Camk2g and G6pc). NGS in Atmin and Pkhd1 KDs identified a common transcriptional network between the two genes. Gene enrichment analysis suggests this common network is associated with immune system processes. Dysregulated genes associated with double KDs showed greater enrichment of processes associated with the actin cytoskeleton, cell cycle and energy metabolism. Loss of Atmin expression negatively impacts the ciliary localisation of Fibrocystin, suggesting that Atmin may be needed for the proper localisation of Fibrocystin to the cilium. NGS in ARPKD kidneys highlights mutations in ATMIN as a potential regulator of disease severity, associated with reduced ARPKD severity. Expression differences in WNT genes may be present between severe and moderate ARPKD and transcriptomic profiling identified candidate diagnostic markers in ARPKD which included MSC, FGA, WNT4, WNT9B and KIF26B. This work indicates that Atmin and Pkhd1 interact in a similar transcriptional network in mice. Atmin is not a transcription factor of Pkhd1 but may modulate its function by governing its ciliary localisation by a yet unknown mechanism. Additionally, ATMIN mutations may modulate ARPKD disease severity, and the amount of differential expression in WNT/PCP genes may be a marker of disease severity.
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Business sustainability: understanding the influence of managers and stakeholders on adopting sustainability practices in Nigerian SMEsThe importance of small and medium enterprises (SMEs) in any economy must be balanced, yet hardly the sector attracts the needed attention for sustainability. This has led to unacceptable high mortality rates for the sector, especially in emerging contexts. Nevertheless, SMEs and sustainability agenda share significant melting pots of disrupting large-scale extreme poverty, among other benefits. Numerous literature supports this and acknowledges SMEs' potential for national employment, investment stimulation and gross domestic growth (GDP). This study aimed to unveil the impacts of managerial characteristics and stakeholders on Nigerian SME sustainability practices to understand SME business sustainability practices in developing countries. To fully investigate these impacts, three research questions enabled the navigation of this project. Firstly, to ascertain the current antecedents influencing SME sustainability practices. Secondly, we quizzed the relationship between the manager's characteristics and Nigerian SME sustainability practices. Furthermore, finally, we sort out how stakeholders influence SMEs' sustainability practices in Nigeria. A qualitative research approach was adopted within an interpretivist philosophical paradigm to construct participants narrated perspectives of sustainability practices. Data were collected from twenty-two (22) Nigerian SME owners/managers and nine (9) stakeholders in semi-structured interviews, virtually. Participants' information was inductively condensed, analysed and thematically framed using the Upper Echelon and Stakeholder concepts. The findings were dimensionally extracted using Gioia's step/order analysis to develop a data structure for each research question. The findings for the current antecedence include the political and governance dimension, the cultural and societal dimension, the economic dimension, and the business orientation dimension. In contrast, the findings for the relationship between managerial characteristics and sustainability practices include observable dimensions and cognitive values. The finding for stakeholder influence on sustainability practices includes the managerial alignment dimension and the dimension of stakeholders’ intervention. Asides from the contribution to knowledge, the result presented national, organisational and managerial practical implications. Diverse organisational and regulatory policy implications were also presented with future research directions.
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Do they know why they know? Student nurses’ experiences of mentors’ judgements of their clinical competence: an interpretative phenomenological studyIntroduction: Expectations of mentors vary in relation to the judgements made in the assessment of student nurses’ clinical competence. It is not clear in the existing literature how the subjective nature of judgements impacts on the student nurse. Aim: This research aims to explore the subjective nature of judgments of student nurse competency by mentors within clinical practice placements and how this is perceived and experienced by adult student nurses. Methods: A qualitative approach, focusing on adult student nurses’ experiences, perceptions and voice was utilised. A purposive sample of 10 participants was recruited and one-to-one semi-structured interviews were undertaken. An interpretive phenomenological analytical framework was employed to conduct the analysis of interviews. Findings: Findings from each participant were discussed in relation to their experiences and perceptions of the impact of mentors’ judgements of the assessment of their clinical competence. A cross case comparison was then undertaken with common themes being drawn across participants aligned to the complexities of being a student, the impact of the mentor role, the contribution of the clinical learning environment, relationship with your mentor and how the mentor’s judgement of the individual impacts on the assessment of their clinical competence. Discussion and Recommendations: The study contributes to the evidence base by being one of the first to specifically focus on the student voice and provide findings in relation to the adult student nurse experiences and perceptions of impact pertaining to the judgements made by mentors of their assessment of clinical competence. Significant findings portrayed the personal and emotional impact this had on participants in relation to their learning, development and progression aligned to the assessment process, mentor’s judgements, mentor’s approach, attitudes and characteristics. Dissemination of findings is key to support the development and further training of practice assessors and supervisors involved in the assessment of student nurse clinical competence. Further recommendations for higher education institutions to address at a Local, Regional and National level were highlighted focusing on student support, coping strategies, practice assessor/supervisor preparation, peer support, and consistency for clinical competency assessment.
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The assemblages, fitness and movements of bats (chiroptera, vespertilionidae and rhinolophidae) in the urban matrixIn this study I examine the assemblages, morphometric differences and movements of bats in urban and suburban green spaces within Birmingham and the Black Country in the West Midlands, UK. This was achieved by undertaking 111 Advanced Bat Licence Surveys at 16 trapping sites, and 91 activity and crossing point surveys at 26 survey sites between 2018 and 2022. Results of the study show that for bats living in this urban matrix, a key factor affecting species richness, diversity and evenness was the amount of grey space at a local (250-500m) scale. Riparian habitats associated with grey space were negatively associated with species richness at a 3km scale. Catch demographics were strongly influenced by the presence of water and swarming opportunities. The data demonstrated significant differences in the size and fat stores of urban and rural populations, with four out of five target species being significantly larger in the urban study area, and fat stores being greater for rural gleaning species, and for urban non-gleaning species. I successfully designed and field tested a novel technique for monitoring the movements of bats along waterways. The data identified commuting routes, hop-on / hop-off sites, crossing points and roost locations, and allowed roost occupancy counts in tunnels. It also demonstrated that risk-taking at barrier crossings is species-specific, with Myotis daubentonii crossing road barriers safely and Pipistrellus pipistrellus doing so unsafely (i.e., over the roads and at risk of direct mortality). The method can provide quantitative data on a landscape scale, on multiple bats, and can be carried out with minimal field training using readily available equipment. These results demonstrate that the effect on bats living within an extensive conurbation is a complex and species-specific, showing that not all species are equally vulnerable to the stresses of living in a conurbation, and indicating that impact assessments, mitigation and conservation efforts should be equally species-specific.
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A solar energy strategy for the Dominican RepublicThe Dominican Republic has a historical crisis in its energy sector due to an unreliable electrical grid system that causes high levels of technical and non-technical losses in transmission and distribution. This is exacerbated by the fact that the country depends on fossil fuels for over 80% of its electricity supply to the population. However, there is enormous potential for solar energy projects due to the country's abundant solar radiation levels. Law 57-07 was enacted to support renewable energy development in the country, and while there has been progress in solar energy implementation since its passage, there have been challenges in their execution. The government must do more to support solar energy development if the country is to reach its 2030 energy goals. To understand why the country has struggled to implement solar energy, an exploratory qualitative research was conducted with a pragmatic philosophy at its core due to the scarcity of sources available regarding the topic in the DR. A systematic literature review was conducted to identify the areas of knowledge involved in the implementation of solar energy worldwide that were lacking in the DR. To understand the specific solar environment of the DR, 14 semi-structured interviews were performed with experts from the Dominican energy sector, selected through purposive and snowball sampling methods. Interviews were the subject of thematic analysis to identify the factors influencing the implementation of solar energy in DR. The study discovered that commitment to international agreements and high levels of radiation are major drivers for the implementation of solar energy in the country; furthermore, the possibility of using off-grid, fast development of projects and steady income along with other 3 more factors were highlighted as driving forces. In contrast, 11 challenges hindering the implementation were also identified with the majority belonging to regulatory deficiencies and a particular case of conflict of interest, which partially prevented the implementation of new projects for several years. Other barriers present in the country are technical deficiencies in the system and how costly some of the technologies are. Nevertheless identifying five main strategies supporting solar energy implementation, the study also highlights deficiencies in their execution; additionally, nine new strategies, based on the experts’ opinions, to improve the implementation were proposed including the definition of a renewable energy standard to improve the project planning, project procurement and ease of financing, which will consequently produce social, economic, and environmental benefits to the DR, such as the increase in public health, creation of new jobs and the stabilisation and affordability of energy prices. Further analysis was performed with an ISM method to determine the interrelationship between the different parameters. All these findings were brought together to develop a strategic framework to support the energy sector’s stakeholders in their efforts to implement solar energy initiatives in the country, which was the aim of the study.
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Married to the cape: Adam West, Batman and signature roles on the small screenThis thesis addresses a gap in scholarship by theorising star status for those performers whose public image is defined by a single televisual role. It proposes the ‘signature role TV star’ as a new category of stardom by evaluating Adam West as a quintessential example of this type of figure. West was best known for playing the titular role in the television series Batman (ABC: 1966-1968), which became a worldwide phenomenon after its debut in 1966. Despite its initial popularity, Batman was cancelled after three seasons and West was unable to develop a lasting career as a mainstream leading man, meaning that his signature role remained the defining aspect of his stardom. West’s connection to Batman continued to manifest, as he occasionally reprised his former role, whilst also taking other parts that evoked his superhero success. Meanwhile, he regularly played himself in a parodic fashion in his latter-day career. West demonstrated that the strong link with a signature televisual role can generate new inflections over time, meaning that he embodies both the advantages and disadvantages of this form of stardom. By theorising West’s star status, this thesis contributes to knowledge in the field of television stardom. Influential theoretical paradigms in this area posit that television is unlike cinema because it creates personalities rather than stars (Ellis, 1992; Langer, 1997). Conversely, Deborah Jermyn (2006) challenges prior theories by analysing Sarah Jessica Parker’s image, suggesting that it may be time to revisit the notion that true stardom needs to be associated with a range of different roles. Although Jermyn links this to the contemporary scene, her notion is also relevant to figures like West who are primarily associated with earlier eras. American television stars of the 1960s and 1970s were particularly likely to be defined by their connection to a flagship part, because this period was characterised by scarcity of viewing options (Ellis, 2002: 39-60), the emergence of repeats as a quintessential televisual form (Kompare, 2005) and a strong cultural tradition of American programmes being exported to nations such as the UK (Rixon, 2006). In conjunction, these factors helped cement the association between prime-time TV stars and popular characters. Such connections are an underexamined area in current TV star scholarship and therefore theorising signature role TV stardom as a distinct type of fame addresses this gap in the field of star studies. The analysis of West as an archetypal signature role TV star is accomplished within a star studies theoretical framework that focuses on his onscreen roles, his promotional and publicity appearances and the criticism and commentary that has been produced about him. Richard Dyer’s star theory (1998) is modified and combined with elements of the work of John Ellis (1992) and Jermyn (2006), to argue that the latter’s suggestion that a theoretical star image can be associated with a single TV role can be expanded to conceive a distinct category of stardom. By employing this approach to theorise West as a signature role TV star, this thesis demonstrates that Jermyn’s observation applies across a broader chronological timeframe than previously recognised. Therefore, the signature role TV star category can be utilised to illuminate the cultural significance of other television stars who have hitherto been overlooked by scholars.
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An investigation into the mechanisms of angiogenesis and breast cancer metastasisBreast cancer survival rates have increased over the years due to early detection and therapeutic efficacy. However, after many years of what appears to be disease-free health, cancer can return in the form of a secondary metastatic tumour. Formation of new blood vessels is a crucial stage in the progression of primary tumours to metastatic tumours. In many cases primary breast tumours that metastasise to the brain occur. Brain tumours are heterogenous malignancies with a low survival rate. Tumours often development therapy resistance by secreting different pro-angiogenic growth factors that allow them to overcome the effect of anti-angiogenic drugs. Thus, characterising the mechanisms that promote tumour angiogenesis may help to stop the development of tumour metastasis. Here it was determined that ATF2 is a downstream molecule activated (phosphorylated) by major pro-angiogenic factors and that its suppression in HUVECs resulted in increased upregulation of Notch signalling pathway (major regulator of angiogenesis) ligand DLL1 and DLL4. Additionally, we investigated genomic changes that may be involved in the development and progression of breast to brain metastasis (BBM). Whole exome sequencing (WES) of 26 breast to brain metastases was carried out. Bioinformatic analysis of WES data identified recurrent genomic alterations in several genes that may be associated with BBM development including an ARFEFG protein family member gene, BIG3. Functional analysis of BIG3 showed that this gene is involved in the regulation of neurotransmitter receptors subunits in the BIG3-knockout MCF-7 breast cancer cell line. Neurotransmitter regulation has been shown as one mechanism through which brain tumours integrate into the neuronal signalling network to promote colonisation of the brain. Results presented here show that investigating the possible mechanisms behind tumour angiogenesis, and the molecular changes that may be involved in metastatic tumour development and brain colonisation offers a better understanding of tumour mechanisms for growth and survival which can offer an opportunity for the development of new therapeutic targets.
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Aberrant expression of miR-133a in endothelial cells inhibits angiogenesis by altering the expression of key angiogenic genesAngiogenesis is a physiological process involved in the formation of blood vessels from pre-existing ones and is tightly regulated by a balance between pro- and anti- angiogenic signals. Disturbance to this balance is associated to human diseases characterised by excessive or insufficient angiogenesis. MicroRNA (miRNA) are small non-coding RNA molecules, which inhibit gene expression by inducing mRNA degradation or suppressing protein translation. Emerging evidence highlights a novel role for miRNAs as regulators of angiogenesis. In endothelial cells miR-133a is expressed at very low levels in physiological conditions however, increased expression of this microRNA in the endothelium has been strongly associated with cardiovascular disease. Previous studies have reported conflicting results regarding the effect of miR-133a expression in endothelial cells during blood vessel formation. The study involved assessing the specific effect of mature miR-133a strands in angiogenesis and the expression of endothelial angiogenic genes. The study evaluated the consequences of aberrant expression of miR-133a in endothelial cells via transfection of miR-133a-3p, -5p, or negative control mimics in primary endothelial cells. This significantly inhibited endothelial cell proliferation, migration, and tubular morphogenesis. The screened gene arrays were performed to identify genes involved in the regulation of signalling pathways, which play a key role in angiogenesis. The results have been further validated by qPCR, which revealed that aberrant expression of miR-133a-3p led to a decrease in the expression of genes encoding pro-angiogenic molecules, whilst increasing those with anti-angiogenic functions. Ingenuity Pathway Analysis of a network of genes differentially expressed in cells harbouring miR-133a-3p, predicted decreased cellular functions related to vasculature branching and cell cycle progression, underlining the inhibitory role of miR-133a-3p in angiogenic cellular processes. The results indicate that enhanced expression of miR-133a-3p in endothelial cells during cardiovascular disease impairs pro-angiogenic cellular processes by altering the expression of specific target genes. Therefore, the results suggest that controlled delivery of miR-133a-3p mimics in diseased endothelial cells may open new therapeutic interventions to treat patients suffering from cardiovascular pathologies associated with excessive or insufficient blood vessel formation.
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Efficacy and tolerance of injectable biologics and antibiotics used out of hospital: systematic review and meta-analysisIntroduction: Out-of-hospital self-care in patients receiving injectable biologically derived medicines (biologics) is reported to significantly improve patients’ quality of life and reduce hospitalisations, but unexpected complications produce some negative outcomes in health and patient experience. Aim: This study aimed to conduct systematic reviews and meta-analyses of published studies to compare health outcomes and therapy complications between long-term injectable antibiotic and biologic therapies compared to placebo or conventional treatment, in and out of the hospital settings for patients diagnosed with inflammatory bowel diseases (IBD), rheumatoid arthritis (RA), psoriasis and infections. Methods and design: To achieve the study aim, five systematic review and meta-analyses were carried out to compare outcomes and complications between long-term injectable antibiotic and biologic therapies to a control therapy. The context was based on ‘out of the hospital’ settings for patients diagnosed with IBD, RA, psoriasis and infections. Results: The first review investigated injectable biologics in treating IBD. The test for overall effect demonstrated biologics were effective compared to control (p< 0.001) and did not cause statistically significant death (p = 0.91) or mild side effects (p = 0.29) but produced more significant severe side effects (p <0.001). The second review focused on injectable biologics in treating rheumatoid arthritis. Biologics were effective compared to control (p < 0.0001) and did not cause statistically significant death (p = 0.24), severe side effects (p = 0.98) or mild side effects (p = 0.48) compared to the control group. The third review was on injectable biologics in psoriasis. The results demonstrated that biologics, while were effective compared to control (p = 0.01) and caused severe side effects (p = 0.02) but mild-moderate side effects (p = 0.17) were not statistically different in both groups. The fourth review looked at patient preference for self-administering subcutaneous injections at home (intervention) vs. intravenous injections in a hospital inpatient or outpatient setting. There was a statistically significant difference between homecare (intervention) and hospital (control) group (p = 0.05). The fifth review was on injectable antibiotics. The results demonstrated that the use of injectable antibiotics, at home (intervention) or in hospital (control) produced similar benefits (p = 0.30 cure and p = 0.90 treatment failure) and harm (hospital admission after and during treatment p = 0.64, p = 0.99 respectively, disease complications p = 0.77 and medications side effects p = 0.15). Conclusion: This research found no substantial disparities in patient outcomes based upon setting. Homecare is an essential option to ensure patient autonomy and wellbeing. The recent global COVID-19 pandemic further highlighted the importance of an option to continue long term disease management without hospitalisation.
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Engineering of composite pharmaceuticals with improved physicochemical and mechanical propertiesTabletting by direct compression (DC) is the preferred method of tabletting as compared to granulation techniques because among other benefits it is simple, quick, and cost-effective. However, most pharmaceutical powders are not compressible via DC due to poor flowability, compactibility, compressibility, and the lack of proper elasticity. As such, formulation scientists use granulation techniques to obtain drug and/or excipient agglomerates with suitable compression properties. Due to challenges associated with the granulation techniques, co-processing using particle engineering techniques has recently become the preferred approach to improve powder physicochemical properties for DC to produce high-quality tablets that can serve the intended therapeutic purpose. Therefore, in this project, composite particles of three drugs (paracetamol, indomethacin, and metformin hydrochloride), which are notoriously known for their poor tabletting and dissolution properties were prepared and investigated to improve their tabletting and dissolution properties. The tabletting deficiency of paracetamol was overcome via composite particles prepared through cooling crystallisation and co-milling. The effect of the milling sequence to improve the flowability of the milled paracetamol composite particles was also investigated. The poor tabletability and dissolution of indomethacin were overcome via milling and freeze-drying. The poor tabletability of metformin HCl was overcome by co-freeze-drying in the presence of polyvinylpyrollidone (PVP). The solid-state properties of the engineered particles were characterised using SEM, laser diffraction, PXRD, FT-IR and TGA. The packing and flowability of the bulk powders were accessed via a density-based measuring technique and the tablets were characterised by friability, hardness (tensile strength), disintegration and dissolution properties. The results showed the composite particles to exhibit modified morphologies, hence remarkable tabletting, and dissolution improvements. Composite paracetamol particles prepared via cooling crystallisation were polyhedral in the absence of additive and irregular lumps in the presence of additives with mean diameters that range from 55.8 ± 0.2 μm to 155.2 ± 2.2 μm. The tablet tensile strength of commercial paracetamol could not be measured because the tablets capped immediately after ejection from the tablet die. Remarkably, composite particles showed ̴ 4-fold an increase in tensile strength as compared to the physical mixture. The composite particles engineered via milling were irregular and become smaller with increasing the milling time from 1 to 15 min (VMD ranged between 81.7 ± 0.6 and 20.4 ± 0.1 μm). Prolonging the milling time up to 20 min did not cause a decrease in particle size in comparison to 15 min (VMD = 22.9 ± 1.0 versus 20.4 ± 0.1 μm) which resulted in a decrease in tablet tensile strength. Generally, the tensile strength of paracetamol composite particles prepared via milling was ̴ 5-fold as compared to the physical mixture, which was better than that of cooling crystallisation. Composite paracetamol particles prepared using cooling crystallisation showed better flow properties (CI = 9.3 ± 0.3 to 15.7 ± 0.2%) than those prepared using milling (CI = 29.67 ± 0.6 to 42.7 ± 4.2%). Investigation of the milling sequence showed a significant improvement in the flowability of the milled composite particles (CI = 41.30 ± 3.1 vs 17.33 ± 0.6%). Although the sequentially milled composite particles generate a strong enough tablet to pass friability, the co-milled composite particles showed better tablet tensile strength than the sequentially milled composite particles (TS = 3.1 ± 0.03 vs 3.9 ± 0.05 MPa). The sequentially milled composite particles indicated a ~4-fold increase in tablet tensile strength in comparison to the physical mixture which was comparable to that of the tensile strength achieved by cooling crystallisation. Indomethacin composite particles prepared via milling showed enhancement in tablet tensile strength (~7-folds) in comparison to commercial indomethacin, and remarkable dissolution (DE (120min) = 91.23 ± 0.25 %, MDT = 9.86 ± 1.4 min and MDR = 1.97 ± 0.05 min-1) as compared to commercial indomethacin (DE (120 min) = 2.733 ± 0.09%, MDT = 57.81 ± 3.1 min, MDR= 0.047 ± 0.01 min-1). As compared to commercial indomethacin the composite indomethacin particles prepared via freeze-drying showed a ~5-fold increase in tensile strength and improved dissolution (DE (120min), 83.987 ± 3.83 versus DE (120 min), 2.733 ± 0.09%). Freeze-dried metformin composite particles were a mixture of irregular and elongated particles which showed improvement (~11-folds) in tablet tensile strength as compared to commercial metformin. In conclusion, highly crystalline composite particles of the drugs with improved physicochemical and mechanical properties were generated with unchanged polymorphic forms using particle engineering techniques (Cooling crystallisation, milling, and freeze-drying). The improved functional properties generated were attributed to the combined effect of change in particle morphology (size and shape), nature of the interaction between drug and excipients and the influence of processing conditions.
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‘Becoming the teacher’ – self and teacher identity in the context of training to teach on a school direct salaried employment-based routeThis study investigates how trainee teachers in England on an Employment-Based Route (EBR), namely School Direct Salaried (SDS), experience ‘becoming’ teachers in the context of the primary school. Drawing upon Beijaard’s (2006) theory that teachers experience ‘a constant becoming’ the study focuses on aspects such as what the trainees bring to their training from their own biographies and backgrounds, and the influence of the school context on the trainees’ experiences. The study conceptualises teacher identity using the theoretical underpinning of symbolic interactionism and specifically the work of George Herbert Mead and Herbert Blumer. Whilst much has been written about teacher identity and the experiences of trainee teachers, there is a significant lack of literature which discusses the experiences of those who are employed specifically to train to teach on EBR. With the gradual move away from SDS towards the Post-Graduate Teaching Apprenticeship (PGTA) route into teaching (DfE 2021a) this study not only contributes to the gap in research and writing which focuses on EBR but also to the training of teachers who enter the profession on such routes. Set in the interpretative constructivist paradigm, case study is used as a design frame for the methodology with the EBR as the case. Questionnaires and small focus group discussions were undertaken as the data gathering tools with the whole cohort of 22 trainees on the SDS route into primary teaching. The findings indicate that trainee teachers bring their experiences of education and the values they attach to it to their training which have an impact upon emergent identity. As the SDS route was specifically established in England for career-changers as well as those who were working in schools as Teaching Assistants (TAs) prior to their training (DfE 2010), the study finds that they experience ‘becoming’ teachers in very nuanced and specific ways. The study discusses the influence of the school environment on the development of teacher identity for trainees on the EBR given that they are employed to train to teach and spend most of their training in the school environment. The thesis recommends ways in which Initial Teacher Training (ITT) programmes might account and plan for the experiences of trainees on EBR and their mentors in developing teacher identity considering how they experience ‘becoming’ teachers differently to trainees on non-EBR.
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An exploration of sustainable business model innovationToday’s business environment is complex; organisations are increasingly forced to adjust. By innovating their business model, organisations have become increasingly capable of creating positive social and environmental value. In research years, the field of business models has gained attention in recent years in both the supporting literature and practice. Initially, the concept was mainly used in the context of technology businesses to describe business processes and evolved as a theoretical concept that outlines an organisation's value creation, delivery and capture processes. Literature acknowledges that innovation in this context looks beyond developing new or improved products to discovering new ways to operate. Advancements in the field of Sustainable business model innovation (SBMI) have helped realise that this type of innovation can help organisations maximise the sustainable value creation and gain competitive advantage while considering the needs of a broader range of stakeholders. This exploratory study aims to expand the knowledge on the SBMI phenomenon. A qualitative approach that relies on semi-structured interviews is applied to answer the research questions guiding the study. Furthermore, the data analysis was supported by tools and techniques such as thematic analysis, total interpretive structural modelling, Fuzzy MICMAC, the triple layered business model canvas, and the value mapping tool. Inspection of the role of the contextual relations between elements of the business environment a firm operates demonstrates how they systematically enables change in the organisations at the strategic and operational levels while influencing the business environment in which organisations operate. The findings highlight how collaborating across the value chain actors and monitoring the context in which the organisations operate allows for the identification of value creation and capture opportunities. This increased sensitivity and engagement also supports them in overcoming pressing challenges such as the lack of an adequate regulatory landscape and poor awareness from the public of the relevant sustainability themes. Identified sustainable strategies can guide the configuration of sustainable business models or serve as a starting point for innovation. The study also reflects on how SBMI implementation unfolds in new and established organisations which guides organisations to tailor processes based on their needs. Furthermore, the evidence suggests that organisations should improve their knowledge of the value implications of their business model. The research findings proposed and evaluated a strategic framework and dynamic capabilities assessment tool.
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The role of antibiotics in preventing infection and its complications in dental surgical proceduresBackground: This project was developed, based upon anecdotal evidence of a wide variety of practices for antibiotic prescribing around dental procedures which include route of administration of antibiotics, timing of the course prescribed when invasive procedures are planned, (before, after or both), length of course prescribed, narrow vs. broad spectrum agents prescribed, use of single or combination of antibiotics and the use of loading doses. The aim of the study was to ascertain if there is scientific evidence to support whether AB use can effectively reduce the postoperative infections after third molar (M3) extraction and dental implant placements (DIP). Method: This study utilised two main designs systematic review and meta analysis and a survey of dentists’ practice opinions. Following PRISMA-P© methodology, two systematic reviews of randomised controlled clinical trials were designed and registered on the PROSPERO© database. Searches were performed using PubMed©, Science Direct™ and the Cochrane© Database, plus the bibliographies of studies identified. The efficacy of prophylactic antibiotic, independent of regimen used, versus a placebo, control or no therapy, on outcomes in post M3 extraction, implant failure due to infection was the primary measured outcomes. Secondary outcomes: other post-surgical complications due to infection and AB adverse events. To provide additional insight and context, the results were compared with data from a survey of practising dental professionals conducted to determine their actual practice and opinions relating to antibiotic use, in the UK across a range of practice settings. Results: In the M3 extraction meta analysis, 16 RCTs were identified and analysed. Antibiotic use was reported to be statistically significant in preventing infection (p <001). Prevention of complications such as dry sockets was not statistically significant (p=0.34) and the NNT was larger than 5 (17 and 97 respectively) which indicates that the intervention not sufficiently effective to justify its use. In the DIP meta analysis, 12 RCTs were identified and analysed. Antibiotic use was reported to be statistically significant in preventing infection (p <001). Prevention of complications was not statistically significant (p=0.96) and the NNT was larger than 5 (14 and 2523 respectively) which indicates that the intervention not sufficiently effective to justify its use. The occurrence of side effects was not statistically significant in M3 extraction (p=0.88) or DIP (p=0.63). NNH was 55 for M3 extraction and 528 for DIP which indicate that the possible harm caused by the use of ABs exists, but it is very small and does not negate the ABs use when required. Finally, 145 general and specialist practicing dentists from different practice settings responded to the opinion survey. There were 42% of participants (n=61) who discouraged AB prophylactic use in M3 extractions in people with no systemic conditions who also preferred postoperative AB use when required. Where, 57.9%) of respondents (n=84) supported the short-term use of ABs (5-7 days) for M3 extraction and 53% (n=77) in DIP placement in patients with no relevant medical history. As an ad hoc finding, dentists reported on the negative impact of heavy smoking and oral parafunctional behaviour on DIP success. Conclusion: This novel combination of methods allowed for more informed conclusions and recommendations. Based on the calculated NNT, the use of prophylactic antibiotics to prevent infection in M3 extraction and DIP intervention was found to be not sufficiently effective to justify its use in patients without underlying medical conditions, which agrees with the fourth European Association for Osseointegration Consensus 2015. Clear clinical assessment pathways such as those used for medical conditions, based on the patients’ dental risk factors (e.g., oral health and bone health), physical risk factors (e.g., chronic or long-term conditions), other health determinants (e.g., smoking, high alcohol consumption) and demographics (e.g., age) are required to prevent unnecessary use of antibiotics. Future research comparing patients with and without underlying medical conditions are required, however a standardised dental infection clinical trials design and protocol are required to improve the quality of research and to unify reporting to allow better future systematic reviews.
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The antihuman unconscious in twenty-first century science fiction cinema: structure of feeling, the political unconscious, and problematising the human in science fiction films produced since 1999This thesis argues that there is an antihuman unconscious present in science fiction cinema of the twenty-first century, which is the result of the tumultuous events of the previous two decades. These events have led many to question if the human species will, or should, survive into the future, and this is reflected in science fiction films of the last twenty years, many of which feature images and narratives of the commodification, vilification, and annihilation of humanity. Utilising Raymond Williams’ structure of feeling, whereby dominant cultural attitudes are challenged by alternative attitudes, and Fredric Jameson’s political unconscious, in which previously repressed ideologies return to the surface of a text, this thesis explores how and why the antihuman unconscious manifests in twenty-first century science fiction cinema. The reasons for the emergence of the antihuman unconscious are connected with the alternative humanisms – transhumanism, posthumanism, and antihumanism – which have reconceptualised and problematised the human in the late twentieth and early twenty-first centuries. To examine how the antihuman unconscious manifests in science fiction cinema, this thesis utilises film genre theory, equating generic elements with elements of the political unconscious and structure of feeling. Science fiction films continue to present humanist narratives despite the emergence of the antihuman unconscious, and close textual analyses of selected films are conducted to determine how that unconscious is signified in visual generic elements which oppose the often humanist narrative elements of the films. The thesis analyses six English-language science fiction films produced since 1999, grouped into three pairs representing each of the aforementioned alternative humanisms. As crises continue to define the first years of the third decade of the twenty-first century, this thesis elucidates how the present upheavals, along with the scepticism directed towards the human species which can be seen in social movements such as veganism and Extinction Rebellion, are reflected in popular media, and contributes to a gap in the literature concerning this scepticism. Theoretically, it presents a synthesis of the political unconscious and structure of feeling that can be used for analysing emerging and alternative cultural trends. Additionally, the thesis contributes to film genre theory with a methodological approach for examining tensions within a genre which considers the opposition of generic visual and narratives elements.
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The effects of bile acid sequestrants on the microbiome in the diagnosis and management of bile acid diarrhoea and post-operative Crohn’s diseaseBile acid diarrhoea is a poorly understood gastroenterological condition despite it affecting an estimated 1% of the general population. It can present concomitantly in other conditions such as post-cholecystectomy and Crohn’s disease, where it is found in over 90% of patients following a terminal ileal resection. A major limitation to recognising and acknowledging this disease is the lack of available diagnostic modalities. The treatment for this condition is bile acid sequestrants although the National Institute for Health and Care Excellence recommend further research to assess treatment response and quality of life outcomes. Furthermore, the aetiology has only recently gained attention with a greater understanding in bile acid modulation and its relationship with the microbiome. There is now increasing evidence that bile acid sequestrants may also alter the composition of intestinal microbial species, thus manipulating disease activity in Crohn's disease. In this thesis, we first set out to investigate the use of a single random stool sample in the diagnosis of bile acid diarrhoea. Secondly, we aimed to profile the gut microbiome in patients with bile acid diarrhoea and determine if bile acid sequestrants altered the microbiome following treatment. Lastly, we investigated whether this treatment could manipulate the gut microbiome and consequently prevent the clinical and endoscopic recurrence of post-operative Crohn’s disease. The results of these studies demonstrated that a single random stool test can be used in patients to diagnose severe bile acid diarrhoea and in those with terminal ileal resected Crohn’s disease. Our study further demonstrated significantly reduced bacterial diversity in patients with idiopathic bile acid diarrhoea and in patients with severe disease. In patients with a negative diagnosis of bile acid diarrhoea, we found an abundance of bacteria that express enzymes that convert primary to secondary bile acids, thereby reducing the symptoms of diarrhoea. Following treatment in those with a positive diagnosis of BAD, we demonstrated an increase in these same bacteria in patients who clinically responded to treatment. Furthermore, in post-operative Crohn’s disease patients, not only were patients more likely to be in clinical and endoscopic remission if taking long-term bile acid sequestrants but they were also found to have a higher abundance of bacteria that exhibit anti-inflammatory properties and reduced abundance of bacteria that is associated with Crohn’s disease pathogenesis. This has important implications in our Crohn’s cohort as not only did we demonstrate disease remission and an improvement in their microbiome following treatment, we further demonstrated this cohort to have the greatest improvement in their clinical symptoms and QoL outcomes. Future work is now needed with larger mechanistic studies exploring the relationship of bile acid sequestrants on bile acid metabolism and microbial composition.
