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ERA is a digital repository of original research produced at The University of Edinburgh. The archive contains documents written by, or affiliated with, academic authors, or units, based at Edinburgh that have sufficient quality to be collected and preserved by the Library, but which are not controlled by commercial publishers. Holdings include full-text digital doctoral theses, masters dissertations, project reports, briefing papers and out-of-print materials.

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Investigating interactions between coinfecting gastrointestinal nematodes and host immunity using meta-analytic, observational and experimental approaches
(2026-05-29) Evans, Michael John; Nussey, Dan; McNeilly, Tom; Kenyon, Fiona
Gastrointestinal nematodes (GIN) have enormous global impacts in humans, wildlife and grazing livestock. Natural infections are composed of co-infections with multiple GIN species, forming an ecosystem of interacting organisms within the host. In this thesis I used meta-analytic, observational and experimental methods to explore this ecosystem, the interactions within it, and the impacts it has on host health. The work focuses on GIN coinfections in sheep, both as a model for the evolutionary ecology of host-pathogen relationships, and to inform decision-making in sheep farming, where widespread anthelmintic resistance necessitates a holistic understanding of GIN coinfection epidemiology. I first conducted a systematic review and meta-analysis of experimental GIN coinfections, which demonstrates that coinfecting GIN tend to interact antagonistically. This means that on average, fewer worms of one species establish when a coinfecting species is also present. This effect is dependent on the infectious dose and is more pronounced in sequential coinfections. The effect occurs across sites within the gastrointestinal tract, suggesting a common mucosal immune mechanism may drive the interactions. I then applied an ITS2-sequence based nemabiome speciation technique to over 3000 faecal samples collected across four years from over 500 sheep living in an unmanaged population on St Kilda. The results show how parasite community diversity and the species-corrected faecal egg counts (sFEC) vary with season, reproductive status and age, in the absence of human intervention. This includes descriptions of the seasonal epidemiologies of relatively understudied species (Trichostrongylus axei, Chabertia ovina and Bunostomum trigonocephalum). In particular I found that Teladorsagia circumcincta and Nematodirus spp. conform to epidemiological patterns previously described in domestic sheep, whereas Trichostrongylus vitrinus is more abundant in lambs in the summer than domestic studies would predict. This epidemiological difference may be a consequence of the antagonistic interaction between Te. circucmcincta and Tr. vitrinus, combined with variation in sFECs in late pregnant females and co-grazing between multiple age classes. I then go on to show that the epidemiology of Tr. vitrinus has important implications for the health and fitness of wild sheep in this system, with significant negative associations between Tr. vitrinus and both the bodyweight and overwinter survival of lambs. This demonstrates the power of the nemabiome approach, with these species-specific measures explaining more variation in bodyweight and survival than are explained by unspeciated faecal egg counts (FEC) or summary measures of parasite alpha- and beta-diversity. The approach also identified a robust, positive association between Tr. axei and August bodyweight, that suggests the impacts of parasites in natural coinfections may be more complex than simply the addition of their individual pathological effects. Given that cross-protective immunity between sites within the gastrointestinal tract may be a key driver of the interspecies interactions in this GIN ecosystem, I then performed an experimental infection to identify the mechanism. This study demonstrated that infection with the intestinal GIN Trichostrongylus colubriformis induces IgG within intestinal and abomasal mucus that cross-reacts the abomasal-dwelling parasite Teladorsagia circumcincta, whereas cross-reactive IgA is restricted to the site of the primary infection. Proteomic analysis indicates that the cross-reactive IgG recognises conserved structural and metabolic proteins unlikely to be exposed in live nematodes and hence unlikely to be effective targets in vivo. However, Tr. colubriformis infection results in upregulation of other immune pathways within the abomasum that are associated with anti-parasite T-helper type-2 (Th2) immunity and are a more likely mechanism for inter-GIN interactions. Together, these findings demonstrate that coinfecting GIN tend to interact antagonistically, most likely via cross-protective immunity that is mediated by immunological changes within the mucosa rather than cross-reactive antibodies. These interactions may be interrupted in domestic systems, with different seasonal epidemiologies for some GIN species observed in wild sheep. These differences may help guide management decisions in domestic flocks and the development of multispecies anti-GIN vaccines. The individual species within the GIN ecosystem also have specific significant impacts on health and fitness of their wild hosts, with demographic feedback on the epidemiology potentially driving host and pathogen co-evolution.
Data-driven approach to evaluating and improving Scottish food environments
(The University of Edinburgh. Royal (Dick) School of Veterinary Studies, 2026-05-29) Kapoor, Deksha; Jaacks, Lindsay; Clemens, Tom; Shields, Kirsteen; Royal (Dick) School of Veterinary Studies, University of Edinburgh: International Scholarship
The persistent rise in the prevalence of diet-related chronic diseases has prompted a shift from traditional individual behaviour change interventions to policies to improve the healthfulness of food environments. The food environment is the interface between people and the wider food system. It encompasses all places where people access food, including retailers, restaurants, pubs/bars, cafés/coffee shops, takeaways, mobile food vans, schools, universities, workplaces, and charities as well as deliveries from these places. Whilst research on food environments in the UK and globally is rapidly expanding, very few studies have been conducted in Scotland. Scotland has disproportionately high rates of diet-related diseases, particularly in socioeconomically deprived areas. To address this, one of the two initial priorities of Scotland’s Population Health Framework 2025-2035 is to develop a whole system approach to improve food environments, ensuring a healthy diet is accessible and affordable to all. The overarching goal of this thesis was to provide evidence to inform data-driven improvements to the Scottish food environment. To achieve this goal, four major aims were developed, each of which forms a chapter in the thesis. The first aim, Chapter 2, was to identify and narratively synthesise recent evidence regarding UK food environments. To accomplish this aim, I conducted a systematic review of 7 databases. After reviewing 31,457 titles and abstracts, I identified 312 articles on the UK food environment published in the past two decades. The majority of articles (32%) focussed on only one of six food environment domains: availability, defined as the presence of specific food items or outlets within a given physical space. Of the remaining domains, 30% of articles assessed product characteristics/quality, 10% assessed promotion, 6% assessed sustainability, 5% assessed affordability and none assessed convenience. With regard to the type of food environment studied, most articles (67%) focussed on food retailers and only 16% assessed restaurants. Finally, obesity was the only health outcome studied extensively. This systematic review highlighted research gaps and laid the foundation for subsequent chapters, each of which addressed a specific gap. Namely, the domain of convenience (Chapter 3) and studies in the geography of Scotland (Chapters 4 and 5) covering the entirety of the food environment, from food retailers to takeaways to full-service restaurants (Chapter 4). The aim of Chapter 3 was to develop a conceptual model and metric for measuring convenience in food environments. This was done through a scoping review on whether and how food environment frameworks integrated convenience and in-depth interviews with food environment experts. Convenience was proposed to be objectively measured as the weekly time spent on food-related tasks. Food-related tasks included planning meals, procuring food, cooking, consuming food and cleaning up. The model also included two sub domains within convenience: product and personal characteristics as well as interaction with other food environment domains. Product characteristics encompass the inherent attributes of a food item, such as the level of processing and packaging, which contributes to or hinders its convenience. Personal characteristics (i.e., income, family size, gender, food choices, cultural beliefs and practices) interact with product characteristics and influence time spent on food-related tasks and whether the food environment is perceived as ‘convenient.’ The aim of Chapter 4 was to characterise food outlets across Scotland and to assess the association between the food environment and neighbourhood deprivation. Using publicly available food business data from the Food Standards Agency (2024), and a novel approach combining text similarity matching with the GPT-4 large language model, I classified 31,135 food businesses as out-of-home (OOH), including restaurants, pubs, cafés and takeaways; retail, including supermarkets and other establishments that primarily sell non-food products with a limited range of food products such as pharmacies; and other, including mobile caterers, charity organisations and home caterers. Most (60%) of the food outlets were OOH, 28% were retail and 12% were other. The density of OOH outlets (1.9 per km2) was over twice that of retail (0.8 per km2). Glasgow City had the highest OOH density (18.4 per km2), while Argyll and Bute, Western Isles and Highlands had the lowest density for both OOH and retail (≤0.03 per km2). Compared to the most deprived neighbourhoods, the least deprived neighbourhoods had more restaurants/cafés (39% versus 23% of food outlets, respectively) and fewer takeaways/sandwich shops (15% versus 23% of food outlets, respectively). This analysis revealed that OOH outlets far outnumber retail in all of Scotland, with takeaways more common in deprived areas and restaurants/cafés in affluent ones. It also highlights unique food environments in different local authorities. The aim of Chapter 5 was to quantify the consumption of home-prepared, ready-to-eat and OOH foods and its association with diet quality among adults 16+ years living in Scotland. Using 24-hour dietary recall data from the nationally representative Scottish Health Survey (2021), I classified all reported food items as home-prepared, ready-to-eat or OOH. Home-prepared foods were defined as those cooked at home using raw ingredients (such as fruit, milk, flour, etc.); frozen ingredients (including frozen vegetables or fruit); ingredients obtained from sources like farmer’s markets, butchers or fishmongers; and items explicitly designated as home-cooked, home-baked or home-grown. Foods and drinks eaten as-purchased (e.g., biscuits, crisps, breakfast cereals, juice and soft drinks) and pre-prepared convenience foods that only require heating (e.g., frozen and refrigerated ready meals) were classified as ready-to-eat. All food and drinks prepared outside the home including restaurants, pubs and cafés, as well as food prepared outside the home but eaten in the home (e.g., takeaway and delivery food) was defined as OOH. The results showed that the weighted mean energy contributions from home-prepared and ready-to-eat foods were similar (~45% of daily calories), while the contribution from OOH foods was relatively low (9%). The highest consumption of home-prepared foods was observed in those aged 65–74 years, accounting for weighted mean (SD) 53% (20%) of total calories. Participants aged 16–24 years were the highest consumers of ready-to-eat foods [weighted mean (SD) 51% (21.5%) of total calories]. Those aged 25-34 years were the highest consumers of OOH foods [weighted mean (SD) 13% (20%) of total calories]. Participants in the least deprived areas consumed a higher proportion of energy from home-prepared foods, while those in the most deprived areas obtained more calories from ready-to-eat and OOH foods: weighted mean (SD) intake ranged from 43% (23%) to 50% (20%) for home-prepared foods across the most to least deprived quintiles; and likewise, from 48% (22%) to 43% (19%) for ready-to-eat foods and 9% (18%) to 7% (14%) for OOH foods. Adults with a larger proportion of energy from home-prepared foods were more likely to adhere to the Scottish Dietary Goals, whilst those with a larger proportion of energy from ready-to-eat and OOH foods were less likely to adhere to the Goals. Overall, the results of this thesis highlight and begin to address research gaps in food environment research in Scotland and provide local evidence essential for understanding Scottish food environments. These findings can inform the development of forthcoming Good Food Nation Plans by local authorities and health boards, as well as national policies to improve food environments in Scotland.
Defining metabolic zonation as a determinant of hepatocyte plasticity
(2026-05-29) McCaffrey, Caitlin; Guest, Rachel; Boulter, Luke
Liver regeneration following injury occurs through several well-defined mechanisms, including the hypertrophy or hyperplasia (proliferation) of epithelial cells and the recruitment and differentiation of hepatic progenitor cells. In specific contexts, experimental evidence suggests that mature hepatocytes have the capacity for transdifferentiation in order to contribute to biliary repair; however, it remains unknown whether all hepatocytes possess this propensity or whether lineage plasticity is zonated within the lobule. This study aimed to investigate whether the position of hepatocytes along the axis of the lobule is a determinant of hepatocyte plasticity. This was achieved through two independent approaches, the first being the design and breeding of two mouse models, which facilitated in vivo lineage tracing of hepatocyte populations from opposite poles of the liver lobule. These mouse models enabled fluorescent labelling of Glutaminase (Gls2)-expressing periportal (zone 1/2) or Glutamine Synthetase (GS)-expressing pericentral (zone 3) hepatocytes, utilising a dual-fluorescent mT/mG CreER-loxP system. Based on established methods described in published studies, intrahepatic cholangiocarcinoma (iCC) was induced via hydrodynamic tail vein delivery of Notch intracellular domain 1 (NICD1) and Akt overexpression, thereby stimulating cell fate change in the two hepatocyte populations of interest. The second approach involved the development of a spheroid culture model from primary murine hepatocytes (PMH) isolated from control mice and lineage-traced Gls2CreER-mT/mG and GSCreER-mT/mG mouse models. This complementary approach enabled the in vitro modelling of zonated hepatocyte gene expression, providing a platform to evaluate hepatocyte plasticity via NICD1/Akt upregulation ex vivo. The data presented in this study reveal that periportal hepatocytes, originating from zone 1/2, specifically those expressing Gls2, undergo transdifferentiation and phenotypic changes that contribute to biliary repair more readily than GS-expressing hepatocytes from the Wnt-high pericentral zone. Additionally, primary murine hepatocyte (PMH) spheroid models not only preserve zonated gene expression profiles of constituent hepatocytes ex vivo but also demonstrate that the zonated phenotypic markers can be influenced through changes in culture media composition. The PMH spheroid platform appeared to recapitulate the transdifferentiation seen in vivo upon NICD1/Akt upregulation, with gene expression analyses indicating a shift from a hepatocyte to a biliary lineage, closely mirroring changes in targeted hepatocyte populations in the mouse models. Importantly, these findings suggest that hepatocyte plasticity in biliary repair is zonally restricted and can be modelled and experimentally manipulated ex vivo, providing new insight into the determinants and modulation of hepatocyte fate in regeneration and disease.
Troubling unexplained (in)fertility: a critical autoethnography of loss and hope
(The University of Edinburgh, 2026-05-29) Meechan, Marie; Wyatt, Jonathan; Prior, Seamus
This PhD project critically examines a re-remembering and re-writing of my personal experiences of being diagnosed with unexplained infertility (UI), and of being unable to conceive and give birth, after twelve years in reproductive medicine settings. It investigates this issue through an autoethnographic social constructionist perspective, using my feminist voice and the map I discovered through these experiences, considering both cultural and societal contexts, as well as my religious environment related to the UI experience. The primary research question examines my personal experiences and the impacts of UI by asking: What is the experience of unexplained infertility (UI)? The sub-question later explores how counselling and psychotherapy can support these processes. This leads to a discussion towards the end of the thesis about the broader topic of counselling infertility. Using vignettes re-remembered and rewritten from my journals over twelve years, I reflect on how I became an object of assisted reproductive technologies and a commodity within the reproductive medicine industry. I also share two examples from my private practice as an infertility counsellor. My writing features three perspectives: my personal experiences as a co-sufferer of UI, my role as an infertility counsellor specialising in this area, and my perspective as a researcher. My study critiques the medicalisation of being unable to conceive and give birth naturally, and questions the UK medical diagnosis, particularly the term “unexplained”. I also challenge the prevailing assumption that all couples can conceive with sufficient and ongoing medical intervention, emphasising the need for a critical examination of when to recognise the limits of such interventions. This exploration aims to highlight the emotional and psychological implications of these medical narratives and to advocate for a more nuanced understanding of infertility that respects individual experiences and choices. Drawing on both my own journals and client examples intertwined with literature and knowledge from the field, my thesis highlights the emotional impacts of undergoing Assisted Reproductive Technologies (ARTs). Critically exploring these various faces and forms of UI reveals different insights and highlights aspects of UI that are not necessarily covered in my own narratives, yet share common themes: shame, stigma, identity issues, and disenfranchised grief. Therefore, this research offers a nuanced understanding of the challenges faced in UI from an insider's perspective, while also critically examining from the researcher's perspective, intertwined with that of the specialist counsellor working exclusively with infertility. Thus, my project ultimately advocates for a more compassionate and supportive approach within both the medical model and among all professionals working with UI and infertility patients/clients. This critical autoethnography not only contributes to the existing literature on the experiences of UI and infertility but also serves as a call to action for improved mental health support for individuals and couples grappling with the complexities of unexplained (in)fertility (UI) and infertility.
Investigating service users and family members experiences of peer support and the implementation of a rural early intervention psychosis service: a research portfolio
(The University of Edinburgh, 2026-05-29) Richardson, Kirsten; Griffiths, Helen; Whyte, Katie
OBJECTIVE: This research portfolio examines interventions for the treatment of psychosis or psychosis related experiences. The systematic review synthesised and critically appraised existing research on the experiences of peer support from the perspective of those directly affected by psychosis or related symptoms, as well as their family members or carers. The empirical mixed methods study analysed the implementation of an Early Intervention Psychosis (EIP) service in a rural Scottish health board. METHODS: A systematic search identified qualitative studies examining experiences of peer support from the perspective of individuals with psychosis, or similar experiences, and their family members or carers. Thematic synthesis generated analytical themes from the findings of the included studies. Fifteen interviews were investigated using grounded theory in the empirical project, alongside the analysis of quantitative service evaluation data. RESULTS: The systematic review identified eight eligible studies. Four analytical themes were conceptualised in a phased structure to reflect the experience of peer support: (1) connecting with peers, (2) learning through mutual support, (3) hopeful progression and (4) influence of setting. The empirical project reported that implementation of the EIP service in a rural health board was as achieved through fidelity to the EIP model being indicated by short waiting times, high engagement and change over time demonstrated. However, long duration of untreated psychosis (DUP) was reported. A grounded theory provides a conceptual framework for understanding how staff rely on collaboration, building relationships and being there for service users and families to navigate the challenges present in delivering EIP in the rural health board. Barriers included social isolation and the influence of restricted access to activities and transport links. CONCLUSION: The systematic review identified peer support as providing an environment which challenges stigma and aids the recovery from psychosis through peer learning opportunities. The findings of the empirical project emphasised the role of relationship-building and collaboration is essential in the effective implementation of an EIP service in rural areas. The influence of rurality on isolation and healthcare remains a challenge recovery and future research should explore this within the context of increasing timely access to treatment for psychosis. The role of peer support should also be emphasised.