Surveillance and Characterisation of the Humoral Immune Response to SARS-CoV-2 in UK Companion Animals during the COVID-19 Pandemic

The 2019 emergence of SARS-CoV-2, the causative agent of the COVID-19 pandemic, resulted in a global public health crisis. The virus is believed to have emerged from bats, via an intermediate animal species into the human population. This significant spillover has laid bare the significant gaps in the scientific community’s understanding of coronaviruses and the surveillance of viruses in animal species. Although SARS-CoV-2 can be considered primarily as a human pathogen, it has been shown to infect a diverse range of animal species, including white-tailed deer, mink and companion animals such as cats and dogs. These animal infections have resulted in severe pathologies in numerous cases, as well as rare instances of animal-to-human transmission. In human diagnostics, reverse transcription polymerase chain reaction (RT-PCR) testing has been the gold standard for identifying active SARS-CoV-2 infections throughout the pandemic. RT-qPCR can also be used to identify SARS-CoV-2 animal infections. This thesis outlines a series of SARS-CoV-2 RT-qPCR-confirmed cases in domestic cats, demonstrating a range of clinical manifestations and outcomes. The occurrence of severe and sometimes fatal infections in both cats and dogs not only raises concerns for animal health, but also for public health, given the close contact between pets and humans and previously documented cases of SARS-CoV-2 zoonosis. RT-qPCR’s utility in animals is limited by challenges in detecting asymptomatic or transient infections. As such, this thesis details the development of an enzyme-linked immunosorbent assay (ELISA) to be used alongside a pseudotype virus neutralisation assay (PVNA), to detect previous exposure to SARS-CoV-2 in companion animal populations. These assays were used in combination to test 5847 residual diagnostic feline samples, finding a neutralising antibody seroprevalence of 4.8%, alongside an ELISA seroprevalence of 13.7%. This large non-neutralising response is likely driven by the production of antibodies against viral epitopes that are not conducive to virus neutralisation, suggesting a complex humoral immune profile in cats following natural infection. Additionally, several demographic risk factors for SARS-CoV-2 seropositivity were identified in cats, including age and breed. A companion serosurvey in dogs, comprising a smaller sample size, demonstrated a comparable overall seroprevalence (4.3% neutralising and 14.3% seropositive on ELISA) but notably lower antibody titres, indicating a weaker humoral immune response relative to cats. Analysis of immune responses in both species showed variant-dependent patterns of antibody neutralisation, which implied the existence of at least two distinct SARS-CoV-2 serotypes. A small serosurvey was also conducted on pre-pandemic raccoon dog sera, uncovering evidence of antibodies against an unknown Betacoronavirus that were capable of cross-neutralising multiple SARS-CoV-2 variants. This finding provides insight into the potential role of raccoon dogs as hosts of coronaviruses with zoonotic potential and underscores the importance of expanded viral surveillance in wildlife. The findings outlined in this thesis emphasise the importance of adopting a One Health approach to pandemic preparedness, integrating human, animal, and ecosystem health research to provide a comprehensive understanding of coronavirus transmission and evolution. The data presented also highlight the requirement for enhanced surveillance of coronavirus infections in companion animals, bats, raccoon dogs, and other wildlife to better characterise the Coronaviridae family and identify potential emerging threats. This knowledge is essential for the understanding of the origins of human coronaviruses like SARS-CoV-2, as well as for informing vaccine strategies, veterinary diagnostics and public health messaging

Elucidating the role of the TGF beta superfamily in metastatic spread of colorectal cancer

Colorectal cancer (CRC) is an aggressive disease and the leading cause of cancer death, characterised by high heterogeneity and various risk factors related to its etiology (1-3). During carcinogenesis, adenomatous polyps, which represent most premalignant lesions (85-90% of sporadic CRC), can develop into CRC (4-6). About 20-25% of CRC patients are diagnosed with metastatic disease, which is associated with poorer survival rates. CRC can spread to various tissues, including lymph nodes, liver, lungs, peritoneum, bones, and the central nervous system (7). The liver is the most common site for detecting metastatic CRC and is involved in 25% to 50% of cases. However, a rare form of CRC with bone metastasis occurs in 3% to 7% of patients; these individuals often have worse survival outcomes, with shorter survival times and limited treatment options (8-10). TGF-β and BMP signalling pathways are crucial mechanisms in tissue homeostasis, promoting cell proliferation and differentiation during crypt formation in the intestine (11-15). Dysregulation of these pathways in intestinal cells can impair their tumour-suppressing functions and facilitate tumour development (16-18). In particular, mutations in TGFBR2, BMPR1A, and SMAD4 have been identified as contributing to CRC carcinogenesis (2, 3, 19-23). Patients with consensus molecular subtype (CMS) 4, categorised based on gene expression signature, are associated with prominent activation of TGF-β, along with stromal infiltration, epithelial to mesenchymal transition (EMT), and angiogenesis, leading to poorer survival outcomes (19). In silico analysis of gene expression levels of TGF-β and BMP signalling components across CRC cell lines using the DepMap database, along with examination of key proteins and their phosphorylation statuses through Western blots, revealed that ligand activation occurs at various levels, with notable activation of upstream receptors such as TGFBR2, ACVR1B, and BMPR1A. Increased expression of signal transduction genes, including SMAD1, SMAD2, SMAD3, and SMAD5, was also observed. Interestingly, although phosphorylation of SMAD1/5/8 was detected in SW620 cell lines (a metastatic CRC cell line), SMAD4, a central element in signal transduction, was found to be downregulated. Apart from the differential expression of TGF-β and BMP signalling in CRC, the investigation of gene expression in these pathways within disease-free bone marrow (BM) cells using the Stemformatics database was also investigated to provide some insight into whether this morphogenic pathway is involved in metastatic spread to the bone. Here we demonstrated high levels of TGF-β and BMP signalling pathways in the bone marrow associated cells, indicating maintenance of homeostasis and serving as a baseline reference for further research. Assessment of epithelial SMAD4 expression in colorectal polyps using immunohistochemistry (IHC) and digital weighted histoscoring with QuPath revealed that low SMAD4 levels in adenomatous polyps correlated with higher grades of dysplasia, different histological subtypes, the presence of metachronous polyps, and served as a prognostic marker. This marker indicated an increased risk of developing metachronous polyps, particularly in the tubulovillous polyp subtype. Additionally, transcriptomic analysis of tubulovillous polyps showed that upregulation of genes involved in protein deubiquitination occurs in polyps with low SMAD4 levels, along with a likely enrichment in tyrosine metabolism, PPAR signalling, arginine and proline metabolism, leukocyte transendothelial migration, and basal cell carcinoma. In CRC, lower epithelial SMAD4 expression was strongly associated with higher tumour stages and increased tumour stroma. Moreover, lower SMAD4 expression in CRC tumours had prognostic significance, predicting decreased cancer-specific survival in CRC patients, especially in right-sided tumours. A combination of tumour SMAD4 levels and stroma percentages suggested that the worst survival outcome was in patients with low SMAD4 expression in the tumour and high stroma content. Transcriptomic analysis also identified downregulation of SOD3 and enrichment of aminopeptidase activity in this group. Differential expression patterns at gene and protein levels, along with phosphorylation activity, were observed across the complex crosstalk of MAPK/ERK, WNT/β-catenin, TGF-β/BMP, and PI3K signalling pathways in CRC cell lines. However, the mechanisms regulating SMAD4 activity in CRC remain unclear.Testing the TGF-β and BMP signalling inhibitor (LDN-212854) in combination with the standard chemotherapy (Fluoropyrimidine; 5-FU) showed synergistic effects on CRC cell viability, cell cycle arrest, cell proliferation, and cell recovery in an in vitro 2D study. Conditioned media from BM and hepatic cells influence changes in CRC behaviour. The 3D bioprinted SW620 spheroids in 2% alginate and 8% gelatin hydrogel supported physiological interactions, spheroid survival and growth, and were used for drug screening, demonstrating efficacy of the LDN-212854/5-FU combination in a more mechanophysical 3D system. Further development of this in vitro 3D model to become multicell by incorporating metastatic CRC culture with BM and hepatic niches would enhancefuture CRC research and drug discovery

Finite-dimensional DG-algebras and Reflexive DG-categories

Summary available

AI-assisted, Raman Activated Cell Sorting (AI-RACS)

Abstract not currently available

If war is the answer, what is the question? A genealogy of ideas in the Greek Just War tradition

Just War theories are shaped by distinct cultures, collective mentalities, and historical developments. However, the existing International Relations literature on Just Wars has not effectively integrated the role of ideas in how actions acquire meaning and legitimacy. Even within the literature on the Just War tradition, there has been a predominant focus on the evolution of Roman ‘Ciceronian’ concepts through the Western medieval system, which became ingrained in Western thought as part of the collective mentalities and experiences of recent centuries. My study tried to address this gap by examining the genealogy of the Greek Just War tradition. The central question of my research is: how did the concept of Just War develop within Greek thought from antiquity to the establishment of an independent Greek state in the 19th century, and can we trace a distinct (Greek) Just War tradition shaped by unique collective experiences, norms, and ideas? References to the Greeks are not ethnological; they refer to the Mediterranean culture centred on the Greek language, concepts, and way of life, which leads to a precise analysis on ideas and practices that construct Just War mentalities. My study demonstrated that the origins of Western Just War traditions can be traced back to Ancient Greek thought and examined how these ideas contributed to the Greco-Roman and Christian synthesis. I explored how Christianity, alongside factors such as geopolitical circumstances, interactions with other cultures, and pre-existing ideas and norms, shaped Eastern Roman practices and created a distinct normative environment, i.e., a different Just War tradition. This environment influenced the evolution of Modern Greek thought, particularly among the Greek diaspora, during the Greek War of Independence, and in the social constructions that legitimised armed conflict as a core element of Greek identity and future Greek security discourses on various domains. Analysing Just War traditions as part of the evolution of ideas across different cultures is both methodologically and ontologically significant. Such an approach enables a deeper understanding of how communities justify warfare, how ideas give meaning to action, and ultimately challenges the positivist view prevalent in modern International Relations, which often treats war merely as a strategic manoeuvre in the game of international politics, rather than as a reflection of diverse cultures. In a globalised interdependent world, the understanding of how warfare is an extension of different communities’ mentality and how ideas legitimise practice is crucial for any aim to improve security discourses, multilateral strategy, and crisis management

The effect of emotional intelligence and emotional regulation in elite military units

Despite widespread application of emotional intelligence (EI) assessments in high-stakes occupations, fundamental theoretical and methodological challenges persist regarding how well current measurements represent the nomological network of EI and their predictive validity. The extent to which existing EI instruments capture a unified construct versus distinct psychological phenomena, remains unclear. Simultaneously, while emotional regulation (ER) theory demonstrates clear links to performance under stress, there remains a critical absence of empirically validated intra-personal regulation interventions that can be effectively deployed in real-world, high-pressure contexts. This thesis addresses these substantial theoretical and practical limitations through two complementary studies investigating EI measurement precision and ER intervention efficacy within British Royal Marine Commandos training. Study 1 examined how well current EI measurements represent the construct by investigating convergent validity between two leading ability-based assessments, the MSCEIT and GECo, and their predictive utility for military training success. Analysis revealed weak to moderate correlations between total EI scores, with similarly labelled sub-scales showing negligible correlations, indicating low convergent validity and suggesting these instruments capture different aspects of EI’s nomological network. Comparative analysis demonstrated that Officer recruits possessed significantly higher EI across most domains compared to civilian reference samples, while non-Officer recruits showed mixed profiles. Logistic regression identified only the GECo emotional management sub-scale as predictive of Officer training success, while the MSCEIT showed no predictive utility in either cohort, and no EI measures predicted non-Officer outcomes. Study 2 evaluated a novel three-component ER intervention (The King Strategy®1) combining resonance breathing, cognitive reframing, and vagus nerve reset techniques through a longitudinal experimental design (n=233). Mixed-effects modelling revealed significant improvements in Commando training performance markers for intervention participants. Under acute stress serials, critical findings included enhanced memory recall when ER strategies were actively employed, with optimal heart rate recovery occurring within 99 seconds; beyond this threshold, memory performance declined significantly. Longitudinally, the intervention increased heart rate variability (RMSSD), reduced perceived stress, enhanced interoceptive awareness, and improved EI sub-scales (management, understanding, regulation) while leaving emotional recognition unchanged. These findings contribute to EI theory by demonstrating measurement challenges within the construct’s nomological network while establishing utility for role-specific applications. The study advances ER theory by providing empirical validation of a multi-modal intra-personal regulation strategy and identifying critical physiological thresholds for cognitive performance under stress. Practically, this research informs evidence-based selection processes and provides a deployable intervention for enhancing human performance in high-stakes environments

Mathematical modelling of active fluids in a channel

Active fluids, such as active nematics, consist of self-driven units that convert energy into directed motion. Examples include suspensions of cytoskeletal filaments, motor proteins, bacteria, schools of fish, cellular layers, and cell tissues. This thesis presents a theoretical and computational study of active nematics using an adapted Ericksen-Leslie dynamical theory, with a focus on understanding how activity, external fields, and geometry influence flow and director patterns in confined systems. In one dimension, we investigate the effects of an orienting field on extensile and contractile nematics under planar and homeotropic anchoring. Extensile systems with planar anchoring exhibit minimal director distortion, whereas contractile systems display significant distortion when the orienting field exceeds a threshold from the initial homeotropic alignment. A kickback effect is observed in contractile nematics, which diminishes in extensile systems as activity increases. Nonlinear analyses reveal uniform, symmetric, and antisymmetric states, with activity enhancing flow and inducing bistability in contractile systems. In two-dimensional channels, we analyse the influence of activity and non-constant boundary conditions. Under inlet/outlet normal flow conditions, low activities produce localised flows, while higher activities generate spatial fluctuations in contractile systems. Extensile nematics at high activity exhibit transitions from unidirectional to bidirectional flow. For inlet/outlet periodic conditions, the system behaviour is similar to that under normal flow conditions. Variation in the splay-to-bend elastic constant ratio leads to transitions from positive to negative flux, demonstrating that active stresses can dominate elastic forces and produce unidirectional flow with positive flux for extensile systems. We also explore time-dependent boundary conditions as a conceptual demonstration of object sensing, showing that the speed of anchoring transitions affects flow patterns: slower transitions delay system activation, while faster transitions reduce bidirectional flows. These results indicate that small local disturbances can produce large-scale flows. In a biological context, such as wound healing, the tissue edge acts as a dynamic boundary where cells actively migrate and reorganise. Our findings on time-dependent boundary anchoring and activity-driven flows suggest that localised changes at wound margins can trigger large-scale tissue flows, mimicking the collective migration observed during wound closure. Overall, this work provides a theoretical framework for understanding how activity and confinement can be harnessed in systems that respond sensitively to local perturbations, highlighting potential applications for active-nematic-based sensing

The creative uses of Irish literature in works by J.R.R. Tolkien

The aim of this thesis is to examine the significant and sustained influence of Irish literature across the corpus of J.R.R. Tolkien’s mythopoeic writings— what is frequently termed as his “legendarium” —and to analyse how he adapted and creatively revised Irish sources in his writings. Some of Tolkien’s statements have given the impression that he did not like, nor was he influenced by, Irish language or literature, and yet scholars have long identified Irish elements in his writings and called for a deeper appreciation of them. This thesis presents the first book-length, systematic critical analysis of the role of Irish literature in Tolkien’s legendarium. It includes the identification and critical analysis of specific works of Irish (and Irish-themed) literature and language study that Tolkien owned, read, is suspected to have read, and/or referenced, including his volumes donated to the Bodleian and English Faculty Libraries at the University of Oxford, and it presents a curated selection of new observations and findings on Irish influences in his writings. As the question of how Tolkien’s work relates to Irish antecedents has been under-researched, this thesis breaks new ground by approaching Irish literature as a major category of Tolkien’s sources and influences

Why high-achieving students avoid STEM careers: a Q-methodology study in China and Scotland

Studying students’ STEM (science, technology, engineering, and mathematics) career aspirations has been a critical area of research for understanding students’ perspectives, motivations, and attitudes. However, many countries face a significant shortage of STEM talent, compounded by the concerningly low proportion of high-achieving students aspiring to STEM-related careers. To investigate why some high-achieving students opt against STEM pathways, this study focuses on China and Scotland—two nations with a high proportion of academically high-achieving students but a comparatively low interest in STEM careers. Despite these shared characteristics, the contrasting educational and cultural contexts of China and Scotland provide unique perspectives for understanding students’ career aspirations. This study employs Q-methodology to explore students’ perspectives on STEM careers, combining Q-sorting and interviews to collect data. A systematic literature review and a questionnaire were used to develop 31 statements for the Q-sorting activity, representing potential reasons for students’ lack of interest in STEM careers. These reasons were framed using the Expectancy-Value-Cost (EVC) model and Social Cognitive Career Theory (SCCT). A total of 15 Chinese and 10 Scottish students participated in the Q-sorting exercise, ranking the statements based on their personal views. Post-sorting interviews followed to allow participants to elaborate on their reasoning and provide additional insights. Data from the Q sorts were analysed using PQMethod 2.35 software, while the interviews underwent thematic analysis using NVivo 14. The analysis identified three distinct factors among Chinese participants: I Lack Competitiveness, I Prefer a Non-STEM Career, and STEM Careers Come at a High Cost. For the Scottish participants, two factors emerged: I Don’t Belong to STEM Fields and STEM Is Not My Dream Job. The findings highlight nuanced perspectives within and across the two cultural contexts, revealing both similarities and differences in how students perceive STEM careers. Findings further revealed the application of the EVC model in describing students’ intention to avoid or leave STEM careers. This study concludes by emphasising the significant value of the EVC and SCCT frameworks in understanding students’ STEM career aspirations. In particular, the EVC framework proved instrumental in analysing the lack of career aspirations or intentions to withdraw from STEM pathways. Practical recommendations for educators, policymakers, and researchers are proposed, including strategies to overcome barriers to STEM career aspirations, foster deeper student engagement with STEM disciplines, and design educational policies that are better aligned with students’ motivations, aspirations, and needs. Furthermore, the study addresses its limitations, offering a solid foundation for future research to examine the intricate relationships between motivational factors, perceptions, and contextual influences within diverse cultural and educational landscapes

The suicide narratives of Silius Italicus

In this dissertation, I examine the theme of suicide in Silius Italicus’ Punica through the following case studies: Saguntum (Punica 2), Capua (Punica 11, 13), Hannibal (Punica 2, 13, 17), Scipio (Punica 4), and Solimus (Punica 9). I analyse recurrent literary features and motifs –civil war, human/object/divine agency, bodily disfigurement, elemental imagery in loci horridi, exile, haunting memory, fides, and pietas– and their connections to Silius’ suicide ideology. I use frameworks provided by Narrative Exposure Therapy to connect these features with textual allusions to Silius’ contemporary Rome and other Latin epics. I observe that Silius portrays suicide as a powerful weapon and instrument for moral action, a form of internal civil war, a form of escape and exile, and a transformative boundary threshold. I conclude that Silius presents an epic ideology of suicide that enabled readers to contemplate the emotional experiences of suicide, and the effects of suicide on one’s physical/cultural identity and environment. These reveal a duality of Silian suicides as desperate acts amid uncontrollable and impossible situations, and as means of reclaiming personal power and control of one’s fate