The diagnostic use of metabolomics for the identification of secondary infections in critical coronavirus disease 2019

Background: Critically ill patients with coronavirus disease 2019 are at high risk of developing secondary infections, which pose a challenge to identify clinically. Empirical antibiotic usage in this group is therefore high. Identification of novel biomarkers of secondary infections would minimise unnecessary antibiotic usage while ensuring that patients with secondary infections receive appropriate antibiotics as early as possible. This project aimed to investigate whether metabolomics could produce a panel of biomarkers capable of distinguishing critically ill coronavirus disease 2019 patients with and without secondary infections. Methods: Blood samples were collected from patients in critical care with coronavirus disease 2019, along with a group of healthy volunteer controls. Using high performance liquid chromatography-mass spectrometry, metabolites which showed significant differences in abundance between patients with and without secondary infections were identified. A panel of metabolites capable of distinguishing Gram positive and negative infections was also explored. Results: A total of 105 patients were recruited to the study, of whom 40 developed a secondary infection during the trial period. The metabolites creatine and 2-hydroxyisovalerylcarnitine were significantly increased in patients with secondary infections, while S-methyl-L-cysteine was significantly reduced. This metabolite panel demonstrated good diagnostic performance with an AUROC of 0.83. The panel of metabolites distinguishing Gram positive and negative infections consisted of betaine, N(6)-methyllysine and four phosphatidylcholines. This panel performed with high accuracy, with an AUROC of 0.88. Conclusion: Metabolomic profiling may be used to identify biomarkers of secondary infections in critically ill coronavirus disease 2019 patients. Investigation of biomarkers for secondary infections in other critical illnesses should be explored

Understanding the role of genetic testing in parental adjustment to their child’s developmental and epileptic encephalopathy or treatment-resistant epilepsy diagnosis

Abstract available at each chapter

The application of the Delphi methodology in intervention development for social withdrawal and Hikikomori

Abstract available at each chapter

Micro-optics: From wormholes to medical applications

Lying within the overarching boundaries of micro-optics, this thesis begins by exploring two different “pixelated” approaches to medical spectacles. The first was aimed as a treatment alternative to surgical corrections for torsional diplopia (double vision due to a relative eyeball rotation around the back-to-front axis). To do this, the spectacles were designed to approximately rotate the view seen through them. In the very basic design consisting of simple wedges (each of which we call a pixel), the component does not actually perform imaging leading to a reduced visual acuity of about 6/420. This was worse than desired, which is why the latter half of the chapter was designated to implementing methods that may improve the visual acuity, consisting of a pupil restriction and a new approach we call derivative control. Using this, the visual acuity was improved to a value of about 6/35, but at the cost of added complexity and bulkiness. The second spectacle pair was designed to help with uncorrected refractive errors by permitting patients to adjust the focusing power of the spectacles through simply rotating two cylindrical lens spirals relative to one another. The combination yields an equivalent Fresnel lens, which is the reason we call these adaptive Fresnel lenses. These were simulated in the ray optical limit, yielding an expected feasible variable range of ±2 diopters. Several configurations were explored where the distances and spiral types were varied, with ray trace simulations confirming the expected view through the adaptive lens. The other half of the text is dedicated to an extension of the previously published ideal lens cloak. The cloaking principles were explored, yielding conditions for which a light ray within the cloak must remain within the cloak and hence travel in a closed ray trajectory. These were used in the theoretical creation of a novel “extreme omnidirectional ideal lens cloak” which hides an object within from all viewing directions. Furthermore, attractor-like properties were found within the cloak, trapping some light rays entering from the outside. These properties were also found in a more realizable cloak we call the “shifty cloak”, which suggests significant similarities between the two cloaks. The shifty cloak was used to construct a Janus device and an optical wormhole, the latter of which was adversely affected by the attractor properties

Gendered power dynamics and the development of Mammisi Temples in Ptolemaic Egypt: reading Cleopatra VII in context

Despite the large body of research dedicated to the reign of Cleopatra VII in Egypt, little of it relies on evidence from Egypt during her reign as its primary source material. What little is referenced is often read out of context and used to prop up themes established by foreign authorship without consideration of potential conflict of interests held by the authors of these texts, or ethnocentric beliefs about Egypt and the Ptolemaic Period as a whole, which may alter both ancient and modern authors’ ability to interpret the information that is being discussed. For this study, I developed an intersectional approach to understanding gendered power dynamics as they developed in Egypt during the Ptolemaic period, their correlation with Cleopatra VII’s reign and method of rulership. This new approach focuses on establishing patterns in religious iconography sourced from Ptolemaic Mammisi Temples and utilizes new analytical tools to allow for a more dynamic discussion of themes of legitimacy, power, and gender which would in turn affect the politico-religious landscape during Cleopatra VII’s reign

Investigating the innate immune barriers that constrain the transmission of coronaviruses

Since the turn of the century, the emergence of three highly pathogenic coronaviruses highlights the importance of understanding coronavirus-host interactions. If sufficient cellular factors are available for a virus to complete its life cycle, genome-encoded post-entry blocks to replication may determine whether virus replication is successful. One such barrier is the interferon response, a signalling pathway upregulating hundreds of interferon-stimulated genes (ISGs), many of which encode proteins with specific and potent antiviral activity. The presence and timing of a functional interferon response is important in controlling coronavirus infection. Thus, identifying ISGs with antiviral activity can provide insights into genetic risk factors associated with coronavirus disease severity and the barriers to coronavirus zoonosis. To identify ISGs that inhibit unmodified coronaviruses, I optimised an arrayed ISG expression screening protocol that utilises immunostaining of the dsRNA replication intermediate and quantification of virus infection by plate-based image cytometry. I screened the endemic coronavirus HCoV-OC43 against multiple ISG libraries encoded into lentiviral vectors, including three published species libraries (human, macaque, bovine) and two newly generated libraries (mouse, bat). This revealed ISGs with known and novel antiviral activity against coronaviruses, including 2’-5’-oligoadenylate synthetase 2 (OAS2). OAS proteins classically activate RNase L via the synthesis of 2’-5’-oligoadenylates, resulting in the degradation of cellular and viral RNA. Alternative splicing generates two OAS2 isoforms, p69 and p71, exhibiting differential antiviral activity. I show that the p69 isoform restricts HCoV-OC43,while the p71 isoform restricts the unrelated picornavirus Cardiovirus A (EMCV) via different mechanisms. The OAS gene family thus enhances antiviral breadth in the host genome by both gene duplication and alternative splicing. This research has provided insights into how coronaviruses interact with the innate immune system

An investigation into the influence of the systemic inflammatory response on treatment response to neoadjuvant chemoradiotherapy in rectal cancer

An abnormal systemic inflammatory response is associated with adverse short and long term outcomes in cancer. Systemic inflammation can be a surrogate maker of the interaction between host immune response and tumour. Systemic inflammation can influence treatment response to chemoradiotherapy. At present there is no reliable biomarker of response to chemoradiotherapy in rectal cancer. This thesis examines the influence of the systemic inflammatory response on treatment response to neoadjuvant chemoradiotherapy in rectal cancer. A dataset of patients receiving neoadjuvant long course chemoradiotherapy (CRT) for non metastatic disease followed by potentially curative resection for rectal cancer was compiled from two prospectively databases of patients treated at Glasgow Royal Infirmary from 2008-2014 and the wider West of Scotland between 2014-2016. Blood results and clinic-pathological data for these patients were collected from electronic patient records to create a comprehensive dataset. Biomarkers of systemic inflammation included: differential blood count; neutrophil to lymphocyte ratio (NLR); haemoglobin; C reactive protein; albumin; and modified Glasgow Prognostic Score(mGPS). Treatment response to chemoradiotherapy was quantified with tumour regression grade, pathological complete response and the neoadjuvant rectal score. I observed white cell count (WCC), NLR and mGPS were not associated with treatment response. Lower haemoglobin and elevated CEA were associated with poorer tumour response. There was no association with changes in WCC, NLR, CRP and tumour response. I observed the development of lymphopenia during treatment but no association with tumour response. I observed baseline anaemia was associated with poorer tumour response and an association between anaemia and systemic inflammation. A significant proportion of my time was in the recruitment and coordination of sample collection for a novel pilot study for the feasibility of protocolised blood and tumour sampling during neoadjuvant therapy. I have not demonstrated an association between serum markers of systemic inflammation and treatment response. I have demonstrated anaemia is a marker of poor response and the association between anaemia and systemic inflammation. This highlights the difficulty in measurements of the systemic inflammatory response from routine blood tests and the importance of more detailed study of markers of systemic inflammatory response which are being done in research settings rather than routine clinical practice. This would help identify reliable biomarkers of treatment response to neoadjuvant chemotherapy and organ preservation strategies

Human behavior-driven robotics and security

Abstract not currently available

Dramaturgy of exile: an autopoietic exploration

This thesis presents a practice-led, dramaturgical inquiry into autopoiesis in exile. It provides a methodology for the recreation or the autopoiesis, of the (writing) self in exile by presenting the emergence of a new languaging of the exilic condition within the exile but, more importantly, outwith the exile, and within the host. Through the researching and crafting of three works of theatre and film the thesis examines the poetic self in exile through written language. The subject is vast and much discussed by many, from classical Greek and Roman antiquity to modernity and postmodernity. The innovation this work offers emerges from writing under the condition of existential peril against “authoritarian and fascist threat” (Stanley, 2024). Through dramatisation, it explores what can happen when language is instrumentalised, decontextualised and turned against its former emancipatory function. Within the chronological impetus of less than one hundred years, there is presently a virulent re-emergence of all five conditions of fascism as set out by philosopher Jason Stanley alongside numerous studies by Arendt, Snyder, Klemperer, Bertrand Russell, Ecco and many others. Exposure to this “descent to fascism” (Snyder, 2025) is taking place through traditional but also technological and complex digital means. In that sense, we are all exiles. As the writer in exile, I have thus addressed a gap in the scholarship by foregrounding the method of autopoiesis as an embodied, dramaturgically situated and performative practice of resistance under contemporary conditions of linguistic, ontological and material exclusion. This work on autopoiesis has been designed as a philosophical pentagon of a Contract of Vulnerability constructed around the wound of exile and its potential for transforming vulnerability into a new language. The first play, LESBOS, examines the term Wound. By exposing the wound, the timing of the wound and the invulnerability of the Antigonian drama, it examines constitutive exclusion and dramatizes the conditions of exilic presence and how these may be regenerated and reimagined. The second play, A Seafarer’s Elegy, is an absurdist piece which examines the condensation of political language. Led by Martin Esslin’s 1960 study on the theatre of the absurd, it considers the sloganification of language and the potential for remaking meaning in a time of depletion of traditional codes of signification. The final piece, A Poetic Constitution for Scotland revisits Scotland as a repository of trauma and contestation and a scene of political resistance. The thesis further examines the function of literature in exile as a precondition of writing and, lastly, problematises translational and extractive poiesis in a moment when the exilic writer is mined for cultural and linguistic capital while simultaneously re-languaging, resisting and producing new dramaturgies in exile

Exploring the global majority and racially minoritised women’s experiences of miscarriage and maternity services

Abstract not currently available