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Person-centred care and relationship continuity in spousal relationships
Get PDFObjective: The purpose of the thesis was to explore the applicability of the concept of person-centred care (PCC) to the care provided by spouses/partners to people living with dementia and to explore whether perceptions of continuity within the relationship influence how person-centred the care is. With a view to laying the foundations for future interventions aimed at enhancing PCC within the home setting, the thesis also provides a systematic review of evidence about the effectiveness of educational interventions in enhancing PCC.
Methods: A mixed-methods approach was used, including a qualitative study exploring the variations across spousal carers in terms of how person-centred their care is when supporting their partner with everyday tasks and a mixed-methods study investigating whether spousal carers’ experiences of relationship continuity is associated with providing a more person-centred approach to care. In the systematic review, few studies involving family carers were found and so the review focused on educational interventions for staff working in dementia services.
Results: Overall, the findings from the systematic review found that there was little evidence that educational interventions alone can provide reliable and substantial improvements in the delivery of PCC in staff. Study 2 suggested that the ideas of PCC are applicable to spousal carers and that there is a significant variability in the degree to which they exhibit PCC. Participants reported little awareness of the concept of person-centred care and little guidance and support from services about how best to provide care. The mixed-methods study (Study 3) found that perceptions of continuity in the relationship were associated with significantly more frequent references to a person-centred approach to care (rho=.39; p=.04).
Conclusion: Spouses/partners do not always provide care that is person-centred and there is scope for improving their understanding of best practice and for providing better support and guidance about how they can best provide care. The systematic review suggested that educational interventions alone may not be adequate for improving the quality of care, and the provision of information needs to be supplemented with other interventions. Focusing on the quality of the relationship, and specifically perceptions of continuity within the relationship, may provide one way forward
Engineering of interfaces in sodium-ion batteries for long cycle life
Get PDFSodium-ion Batteries (SIBs) present a wealth of possibilities for cost-effective and environmentally friendly energy storage solutions. One challenge to close the gap is the insufficient cycling lifetime.
To maximize their potential, new cathode materials with high specific capacity and stable structures are required. Cobalt-free sodium transition metal oxides of O3 type are promising candidates as cathodes for use in SIBs, owing to their high specific capacity, appropriate operating potential, wide availability of transition metals, and facile synthesis methods that can be inherited from lithium-ion batteries. However, layered oxides suffer from irreversible phase transitions and structural instability, hindering long-term cycling stability. In this work, innovative approaches for improving the cycle life of layered oxides (O3-type NaNi1/3Fe1/3Mn1/3O2 in specific) and the final full-cell battery are investigated through structure tailoring, morphology engineering, and full-cell design. Through in-depth analysis and experimentation, this research aims to establish an effective path toward the practical utilization of enhanced sodium-ion batteries.
Firstly, the flexibility of Sn4+ dopant, a non-transition metal, was explored, with the aim of modifying the material’s bulk structure by suppressing the host rearrangement and TMO2 gliding. A series of Sn-modified NaNi1/3Fe1/3Mn1/3O2 cathode was synthesized and characterized, and 8%Sn-modified NaNi1/3Fe1/3Mn1/3O2 cathode exhibited outstanding cycling performance owed to the simultaneously stabilized bulk structure and interface. The underlying mechanism was studied through an extensive analysis (Chapter 4).
Secondly, the physical properties of the synthesized materials are significantly dependent on the synthetic conditions, which in turn affect the final electrochemical performance. Here, the effect of synthesis conditions (pH, molar ratio of ammonia/metal precursor salt, and stirring speed) upon the particle size and morphology of NaNi1/3Fe1/3Mn1/3O2 particles was investigated for the first time. Statistical methods and regression analysis were employed to provide valuable insights into the relationship between synthesis parameters and materials properties. Optimized conditions were derived from the obtained regression models, and particles synthesized with optimum parameters displayed uniformly distributed particle size together with a threefold increase in cycling performance (Chapter 5).
Finally, the optimized NaNi1/3Fe1/3Mn1/3O2 cathode synthesized under the optimum parameters together with 8% Sn modification was fabricated into 8%Sn-NaNi1/3Fe1/3Mn1/3O2 || Hard carbon full cells to verify the practical application. The effects of the N/P ratio (areal capacity ratio between negative and positive electrode) on the material utilization, initial capacity, first Coulombic efficiency, and cycling performance were investigated by using three-electrode cells. The failure mechanisms under different N/P levels were preliminary discussed. The fundamental reason for battery failure is that the electrode potential of the positive or negative electrode exceeds the critical window. Cells with an N/P ratio of 0.9 perform the best cycling performance due to the suppression of irreversible phase transition and sluggish kinetic reactions in the cathode at voltages above 4.1 V (Chapter 6)
Defining mechanisms and new treatments for headache in raised intracranial pressure
Get PDFHeadache disorders are common and debilitating neurological conditions. While treatments can alleviate pain, our understanding of the mechanisms triggering attacks is incomplete. Evidence suggests that metabolic dysfunction may play a role in headache development and susceptibility, with fasting being a suspected migraine trigger, highlighting the importance of glucose metabolism. Identifying these energy-related mechanisms could lead to targeted interventions. Elevated intracranial pressure (ICP) can also cause headaches that are migraine-like, as seen in idiopathic intracranial hypertension (IIH), which additionally features metabolic disturbances. Although migraine treatments have exhibited some efficacy for raised ICP headaches, there is a lack of targeted therapies for IIH-related headaches, and the underlying mechanisms are poorly understood.
Cortical spreading depression (CSD) is a pivotal mechanism involved in migraine and has been established as energetically demanding. This thesis explored the metabolic consequences of CSD by analysing calcium signalling, mitochondrial activity, and metabolite profiles in an ex vivo acute brain slice model. This thesis also investigated the influence of ICP on headache mechanisms including CSD using a rodent model of raised ICP. Additionally, it examined the impact of reducing ICP with glucagon-like peptide-1 (GLP-1) receptor agonism and blocking calcitonin gene-related peptide (CGRP), a key factor in migraine.
Brain slices showed astrocytic calcium movement and markers of increased aerobic and anaerobic glycolysis in response to CSD. When challenged with glucose deprivation, mitochondrial activity was downregulated, potentially indicating exhaustion. Interestingly, there was evidence of metabolic adaptability in glucose absence, suggesting the utilization alternative energetic pathways and substrates under metabolically stressful conditions. These findings enhance the understanding of the role of metabolism in CSD but also unveil altered energetic pathways, thereby identifying potential targets for therapeutic interventions.
The rodent model of raised ICP identified altered pain behaviour (indicative of changes in trigeminal sensitivity), disrupted cortical blood flow (CBF) and CSD responses. GLP-1 receptor agonism reduced ICP which was associated with prevention of pain behaviours and demonstrated restored cortical and CBF CSD responses. CGRP receptor antagonism ameliorated cranial pain behaviour, indicating a role for CGRP in driving pain responses in elevated ICP. Reduction of ICP through GLP-1R agonism and nociception attenuation via CGRP antagonism could represent potential therapeutic approaches. This pre-clinical evidence highlights the efficacy of therapeutics in managing headache behaviours and pathways, essential for guiding future clinical trials given the lack of targeted therapies for elevated ICP
Existentialism, the absurd and contemporary theatre
Get PDFOver sixty years have passed since the Theatre of the Absurd was first codified by theatre critic Martin Esslin, in that time, many different artistic movements have emerged and shaped theatrical orthodoxy. Furthermore, it has been an equally long time since the playwrights whose work has been characterised as Absurdist and Existentialist defined and expanded upon their own fields. The purpose of this research project is to explore how and why contemporary theatre continues to incorporate core ideas and themes from the Theatre of the Absurd and Existentialism to explore twenty-first century issues.
A definition of 'Absurdism', 'Existentialism', and 'the Theatre of the Absurd' will be provided in the first chapter to establish a foundation for the research. The rest of the thesis will be dedicated to the analysis of fourteen British playwrights, each chosen for the way in which they utilize, incorporate, and apply both the Absurd and existential thought. They include Caroline Horton's 'All of Me' (2016); Anthony Neilson's 'Realism' (2009); Caryl Churchill's 'Far Away' (2000), 'A Number' (2002), Escaped Alone (2016), and 'Love and Information' (2019); Dennis Kelly's 'Debris' (2004), 'Orphans' (2009), 'The Gods Weep' (2010), and 'Girls and Boys' (2018); Ella Hickson's 'The Writer' (2018); Mike Bartlett's 'Cock' (2009) and 'Albion' (2017); and Jez Butterworth's 'Jerusalem' (2009). In all, they represent a wide range of differing perspectives that span the last two decades of British contemporary theatre. Structurally, these plays will be divided according to the overarching themes of existential uncertainty, environmental exploitation, patriarchal violence and male toxicity, familial violence, racial tension,and identity, with each theme corresponding with a dedicated chapter.
The thesis concludes that the core themes within Existentialism and the Absurd remain pervasive despite the various theatrical and artistic movements that have emerged since. Furthermore, this thesis will also showcase how both Existentialism and the Absurd can be applied to better understand and tackle twenty-first century issues
The development of an intersectional methodology for a social constructionist ecofeminism
Get PDFThe fundamental claim of ecofeminist theory is that there are connections between the oppressions of women and nature. With climate change causing ever increasing concern, and feminism having moved into a fourth wave, ecofeminism offers important insights into injustices across both human and nonhuman spheres. However, there have been significant criticisms posed to ecofeminist work, notably that it tends towards essentialism in its categorisation of ‘woman’ and ‘nature’. Whilst social constructionist ecofeminists, like Val Plumwood, have sought to develop ecofeminist theory to not fall foul of these problems, with contemporary ecofeminists such as Greta Gaard noting the value of intersectional ideas within ecofeminist theory, intersectionality as an approach for overcoming essentialism has not yet been embedded in ecofeminist thought in a way that is structural and explicit. I propose that centring intersectionality disrupts essentialised categorisation by highlighting the complex interplay between privileged and oppressed identity categories. Therefore, this thesis seeks to contribute to this shift away from essentialism in ecofeminist literature by developing a novel intersectional methodology for ecofeminist theory. The method employed throughout the research project was within the political and theoretical traditions of surveying literature, and this enabled a collecting of research which highlighted that applications of intersectionality in feminism have tended not to include the nonhuman within their scope, whilst ecofeminism possesses the architecture to address these intersections. The project was centred on methodology- building, and subsequent methodology-testing through an exploration of feminised proteins. This intersectional methodology, designed for ecofeminist theory, is applied to the case study of the egg and dairy industries to respond to their related intersecting injustices. I suggest that an intersectional methodology allows us to understand the complexity of oppression in a way that leads to recommendations of praxis that can more successfully ameliorate these oppressions
A mycobacterial glycoside hydrolase 76 enzyme enables arabinomannan release to signal exit from lag phase
Get PDFA key component of the mycobacterial cell envelope are the glycolipids. These molecules play important roles in both structural support and modulation of the host immune system. One of the major phospholipids produced by mycobacteria is phosphatidylinositol. This molecule can be glycosylated to produce phosphatidylinositol mannosides, as well as lipomannan and lipoarabinomannan. These mannosylated glycolipids make up the majority of the lipids in the cytoplasmic membrane. However, within the capsule of mycobacteria are lipid-free glycans thought to be derived from lipomannan and lipoarabinomannan. Currently, there is no explanation as to how arabinomannan and mannan are released from their lipid anchors. In this thesis, a glycoside hydrolase family 76 enzyme is identified which cleaves lipomannan and lipoarabinomannan and drives export of the carbohydrate domains to the capsule. In addition, this thesis demonstrates that the loss of this enzymes activity results in a loss of capsular arabinomannan. Furthermore, the loss of arabinomannan leads to an increase in lag phase and significantly slower exponential growth. This thesis provides evidence that arabinomannan acts as a signalling molecule which triggers the transition from lag phase to exponential growth. The findings presented in this thesis will serve as a basis for a better understanding of the digestion of mycobacterial glycolipids and the trafficking of these molecules to the outer most layer of the cell. This may lead to a more detailed appreciation of the role lipoarabinomannan and its derivatives play in host- pathogen interactions and bacterial physiology
Utility of small extracellular vesicles in informing biological responses to exercise and ageing
Get PDFSmall extracellular vesicles (sEVs) are nano-sized particles containing proteins, metabolites, lipids, and RNA that can be transferred between cells. sEVs have been implicated in various biological processes. These include exercise, ageing, and cellular senescence. Understanding how sEVs are impacted by these processes may be informative of how these processes work. Additionally, due to the significant release of sEVs that has been reported as part of the senescence-associated secretory phenotype (SASP), and the relative clinical accessibility of circulating sEVs, it may be possible to identify candidate biomarkers of senescence. This thesis investigated the impact that exercise (both acute and chronic), ageing and senescence have on the sEV count and proteome, with an overarching aim to determine the utility of studying sEVs in these
wider contexts. Chapter 2 aimed to determine whether there were significant differences in circulating sEV number after a bout of high intensity cardio-based exercise. This was done by using single EV particle analysis to count circulating sEVs in response to high intensity interval
exercise. It was found that there was a statistically significant release of sEVs positive for the CD9, CD63, CD81 and CD41a tetraspanins. Chapter 3 aimed to further investigate the proteome of sEVs released found within sEVs released during senescence, and whether any of these could have been candidate biomarkers. Using three different methods of inducing senescence, we tested senescence-derived sEVs using nano ultra-high performance liquid chromatography-tandem mass spectrometry (nano UHPLC-MS/MS). Experimentally induced senescence effected a large change in the sEV proteome with NIT2, CARS, EEF1A2, GSTO1, PGAM 1, PGAM 2 and NAMPT identified as candidate biomarkers of senescence.
Finally, Chapter 4 aimed to identify whether there were any significant quantitative or proteomic differences in circulating sEVs in response to ageing or chronic exercise. This was achieved by examining the impact of ageing and chronic exercise on sEVs in vivo, via single EV
particle analysis on young plasma, older adult plasma, and Masters athlete plasma. Although there were significantly fewer CD9 positive sEVs in older adults than in the young cohort, and significantly less CD9 protein expression in Masters athletes compared to the young cohort, there was no large difference in number of circulating sEVs between cohort considering age or chronic exercise. In addition to no major differences in sEV count, nano UHPLC-MS/MS revealed only minor differences in the circulating sEV proteome, including no difference in the candidate markers of
senescence. These works indicate that although sEVs are released in response to acute exercise and senescence, there are limited differences in sEV count and protein cargo between young, old and Masters athletes implying a broad look at sEVs does not inform the ageing process nor the impact of lifelong exercise
Beam intensity effects on the measurement at NA62
Get PDFThe ultra-rare decay, precisely predicted in the Standard Model, is a gateway into exploring new physics at mass scales unattainable at present collider experiments. The NA62 experiment at CERN aims at measuring the branching ratio of the decay to a precision of 15% with any deviation from the Standard Model prediction hinting at New Physics.
A Cherenkov detector (CEDAR) is used in NA62 to identify a minority component of particles (kaons) in an unseparated hadron beam. The optical design for a new CEDAR detector optimised to work with hydrogen as radiator gas, Cedar-H, is presented. Cedar-H has been commissioned and installed into NA62 with more than satisfactory performances and a 20% increase in light yield.
The single event sensitivity for the decay with data collected in 2021 is computed as B = (5.00 ± 0.13) × 10. Studies of each component entering into this figure and their variation with the intensity of the NA62 hadron beam are performed. A new optimal beam intensity to maximise the number of events collected is discussed
Investigation of the mechanisms that link pre-mRNA splicing to NMD and translation in Schizosaccharomyces pombe
No full textPre-mRNA splicing is a cotranscriptional mechanism that precisely removes intronic sequences from pre-mRNA in eucaryotes. The Exon Junction Complex (EJC) is a highly conserved protein complex that binds upstream of the splice junction on mRNA following splicing and remains during nuclear export bound until translation begins in the cytoplasm. Particularly, the EJC has been highly studied for its role in nonsense-mediated mRNA decay (NMD) in recognising premature termination codons (PTC) on mRNA. Still, its exact role in NMD and gene expression in general remains elusive. In Schizosaccharomyces pombe, three proteins - Fal1 (eIF4AIII in mammals), Y14, and Mago - are conserved. Since intron recognition and splicing prevalently occur co-transcriptionally, EJC deposition is expected to occur mainly on the nascent mRNA. To understand the association of the core components of the EJC with nascent RNA, chromatin immunoprecipitation (ChIP) and ChIP-seq were used. The results demonstrated that the EJC components associate with genes in a transcription-dependent manner that occurs by association with nascent RNA. However, Fal1 associates nascent RNA independently of Y14 and Mago, and only the association of Mago and Y14 is interdependent with each other. Given the association of these proteins to transcription sites, I investigate whether they play a role in transcription by assessing whether there are perturbations in Pol II association, examined by ChIP of either total Pol II or Ser2 or Ser5 phosphoisoforms. The results indicate that the association and phosphorylation of Pol II with genes are affected by the deletion of Y14.
The EJC model was originally put forward to explain how pre-mRNA splicing could affect NMD which is a process that takes place in the cytoplasm. Here, given the results suggesting the EJC association is splicing independent, we consider whether other mechanisms could explain the link between splicing and NMD. A model that has been considered is that the ribosome scans the nascent RNA of the transcripts. The prediction is that on those transcripts that carry introns, there is a potential physical interaction between the translating ribosome and the spliceosome as well as with the Pol II. Following this challenging hypothesis, in the final part of my project, I examined directly whether translation inhibition affects transcription. The experiment involved brief incubation of the cell cultures with two translation inhibitors - cycloheximide (CHX) and puromycin (PMY) and see whether these affect Pol II loading in a translation-dependent manner. The results indicate that translation inhibition causes a dramatic change in Pol II association with genes. While these results will need to be validated by additional experiments, they do indicate they are consistent with the model that translation of nascent RNA could affect transcription and therefore luckily pre-mRNA processing. Where this interpretation is correct, it raises the possibility that the recruitment of the EJC proteins and the splicing might also be affected by translation inhibition
Ordinary and modular representation theory of truncated current Lie algebras
Get PDFIn this thesis, we study the representation theory of truncated current Lie algebras associated to Lie algebras of reductive groups. After giving the necessary preliminaries, we begin by considering the representation theory of these Lie algebras in characteristic 0 by defining a generalisation of the Bernstein–Gelfand–Gelfand category for reductive Lie algebras and using this to study the problem of computing composition multiplicities
of Verma modules. In particular, we give an inductive procedure to compute these multiplicities in terms of the composition multiplicities of Verma modules for reductive Lie algebras, which are famously given by the Kazhdan–Lusztig polynomials. These results have been published in [7] and [8].
We then move on to consider the representation theory of truncated current Lie algebras in prime characteristic. Here, after proving some elementary structural results such as the classification of semisimple and nilpotent elements, we tackle three main problems. The first is on upper and lower bounds for the dimensions of simple modules; we give an upper bound on the dimensions of simple modules for all -characters and a lower bound for certain -characters. Then we classify simple modules for certain p-characters. Finally,we finish by computing the composition multiplicities for projective modules for the restricted enveloping algebras of truncated current Lie algebras, and show they can be given in terms of the composition multiplicities of baby Verma modules for the corresponding reductive Lie algebra. These results are the subject of the preprint [9]
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