http://theses.ncl.ac.uk/jspui/handle/10443/96 2026-06-10T20:19:58Z http://theses.ncl.ac.uk/jspui/handle/10443/6808 Title: An action research approach to relationships and sex education (RSE) in the digital era Authors: Alderson, Ashleigh Abstract: Young people increasingly rely on digital technologies to communicate with peers, and explore their sexuality, much to the concern of adults. However, adults’ anxieties over young peoples’ technology use often results from morals and technopanics, failing to consider the opportunities that technology can offer. Morals and technopanics often translates into education, with Relationships and Sex Education (RSE) focussing on harms and at times even victim blaming young people for harms experienced through technology. This research utilised an Action Research (AR) methodology to understand, and respond to, the impact of digital technology, namely TikTok, on relationships among young people. The first AR cycle involved semi-structured interviews with 12 young people. Findings include opportunities that TikTok offers to marginalised young people including LGBTQ+ communities, and potential harms including addiction and what I termed ‘algorithmic segregation’ whereby those who do not fit the platforms’ ideals gain less visibility as content creators. In response to these findings, I developed an algorithmic awareness intervention designed for the RSE curriculum. Feedback on the intervention was sought through an online survey involving RSE teachers. The survey’s findings revealed that there is no ‘one size fits all’ as each school delivers RSE differently. The intervention could not be employed within schools due to the Covid pandemic. It was instead employed within a youth group context in a deprived area of the North East of England as the final AR cycle. The findings of this AR cycle highlight the need for tailoring inclusive learning resources to the diverse needs of learners specifically accounting for the needs of SEN learners and boys who are often forgotten within RSE, which typically focuses on, and at times pathologises, girls and their behaviour. I discuss the findings from this research and provide recommendations for policy, education, healthcare, and future research. Description: PhD Thesis 2025-01-01T00:00:00Z http://theses.ncl.ac.uk/jspui/handle/10443/6806 Title: haracterisation of the involvement of angiotensin-signalling pathways in anthracycline-induced cardiotoxicity Authors: Alsuhaibani, Ray Abstract: Delayed cardiotoxicity is a major clinical issue with anthracyclines and cancer treatment, associated with development of life-threatening heart failure. Clinically, drugs interfering with the angiotensin-signalling pathway have shown promise for mitigation of anthracycline induced cardiotoxicity (AIC). However, the mechanistic basis for this response remains unclear. In this study, both angiotensin II stimulation and exposure to sub-therapeutic concentrations of the anthracycline doxorubicin have been shown to induce cellular hypertrophy in human cardiomyocyte cells, an effect associated with a significant upregulation of expression of the angiotensin receptor (AT1R). In contrast, no such morphological changes were observed in primary human cardiac fibroblasts (HCF). Surprisingly, despite no observable structural change being detected in HCF, exposure to doxorubicin did cause an increase in AT1R expression. Such an observation indicating a potential interplay between these two cell types of the myocardium in AIC, involving crosstalk of the angiotensin-signalling pathway. The importance for AT1R in the cardiomyocyte response to doxorubicin was confirmed by knockdown of AT1R using small interfering RNA (siRNA), which mitigated the hypertrophic response. From a therapeutic perspective, the hypertrophic response of cardiomyocytes was mitigated by pre-exposure to the angiotensin receptor blocking drug telmisartan, offering an explanation for the cardioprotective effects of blocking angiotensin-signalling in AIC. Together these findings support an involvement for angiotensin signalling in drug-induced hypertrophy and subsequent cardiotoxicity, with scope for interaction of this pathway for mitigation of chronic cardiotoxicity in the clinic. Description: Ph. D. Thesis 2025-01-01T00:00:00Z http://theses.ncl.ac.uk/jspui/handle/10443/6805 Title: A Longitudinal Study of Factors that Impact on the Quality of Life of Intestinal Failure Patients treated with Home Parenteral Nutrition Authors: Kirk, Colette Abstract: Background: Home parenteral nutrition (HPN) is a lifesaving therapy for patients with intestinal failure, aiming to improve survival and quality of life (QoL). However, patients often experience burdensome symptoms including fatigue, pain, gastrointestinal discomfort, and social isolation. Complications such as intestinal failure-associated liver disease and multi-morbidity further compromise QoL. This project investigated the impact of HPN on QoL and explored the role of nutritional status and liver function. Methods: A multi-phase study was conducted, including a systematic review, national survey of healthcare professionals (HCPs), and a prospective longitudinal cohort study of adults on HPN across three centres. The primary outcome was change in QoL scores over 12 months. Secondary outcomes included the influence of liver function, nutrition, parenteral nutrition (PN) composition, and muscle function on QoL. Results: The systematic review identified limited high-quality evidence to guide nutrient provision in adult HPN. The HCP survey revealed inconsistent use of QoL tools and limited integration of Patient Reported Outcome Measures (PROMs). In the longitudinal study (n = 199 at baseline; n = 145 at follow-up), QoL remained significantly impaired, particularly in physical and functional domains. Sociodemographic factors such as employment and higher education were consistently associated with better outcomes across EQ-5D, SF-36, and HPN QoL scores. Employment was associated with improved general health and EQ-5D VAS (β = 10.8, p = 0.001; β = 12.5, p = 0.005). Handgrip strength was linked to reduced fatigue (β = 1.2, p = 0.004), while skeletal muscle mass predicted improved physical functioning (β = 1.66, p = 0.014). Phase angle was associated with lower immobility scores and higher emotional functioning (β = –9.2, p = 0.100; β = 7.5, p = 0.024). Conclusion: QoL in HPN is shaped by a complex interplay of nutritional, clinical, and psychosocial factors. PROMs should be integrated into routine care to support multidisciplinary, patient-centred service development. Description: PhD Thesis 2025-01-01T00:00:00Z http://theses.ncl.ac.uk/jspui/handle/10443/6801 Title: From origin to lifespan: Unravelling early human developmental haematopoiesis and macrophage heterogeneity Authors: Goh Kai’en, Issac Emmanuel Abstract: This thesis explores early human developmental haematopoiesis, emphasising the integral roles of the extraembryonic yolk sac (YS) in generating the first blood and immune cells, including macrophages, and providing nutritional support to the embryo. Much of our current understanding of early haematopoiesis derives from pivotal studies in model systems. However, the application of single-cell genomics technologies have enabled this study to deliver a detailed multiomic characterisation of the multifunctional role the YS plays in early human development with temporal resolution. As part of the Human Cell Atlas, I co-led a collaborative, multi-site effort to construct a time-resolved multiomics atlas of the human YS from the 3rd to the 8th post-conception weeks. This atlas integrates protein and gene expression data and is augmented with existing scRNA-seq data from eleven other prenatal tissues, including crucial haematopoietic tissues like the liver, bone marrow, and Aorta-Gonad-Mesonephros (AGM). This integrative approach facilitated the mapping of human early immune and blood development. Our findings elucidate the unique spatiotemporal characteristics of YS haematopoiesis fundamental to the emergence of the first blood and immune cells. Our analyses reveal YS evolutionarily conserved roles in metabolism, coagulation, vascular development, and early haematopoietic regulation, with these functions gradually ceded as development progresses. We detailed the dynamic emergence and decline of YS Hematopoietic Stem and Progenitor Cells (HSPCs) which originate from YS hemogenic endothelium (HE), illustrating the earliest wave of haematopoiesis. We also identified a YS-specific macrophage production pathway, and a pre-specified, TREM2+ microglia-like macrophage subset across prenatal tissues. This work illuminates a previously obscure phase of human development, establishing the YS as a vital multifunctional organ. Building this map of early haematopoiesis offers valuable insights into cellular differentiation pathways specific to early life, paving the way for novel tissue engineering strategies and cellular therapeutic avenues. Description: PhD Thesis 2025-01-01T00:00:00Z