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Item Restricted The Impacts of Western Theories: Application to Professional Social Work Practice in Saudi Arabia(Saudi Digital Library, 2025) Barasayn, Nouf; Clark, JulieThis study examines the impact of western social work education on decision-making among Saudi Arabian social workers within an Islamic context. Specifically, it investigates the integration of theoretical frameworks learned at university into practical social work, exploring factors such as professional experience, religious beliefs, and cultural influences that may shape decision-making. Research questions address whether social workers recall and utilize theories from their studies, the influence of practicing in an Islamic society, and potential conflicts between Western theories and Islamic values. Findings reveal that while social work education has significantly shaped professional practices—particularly through problem-solving skills and systematic approaches—many social workers are also guided by religious values in their practice. The research highlights that, for the majority, Western social work principles, including client dignity, respect, and autonomy, align with Islamic values, suggesting successful integration of these frameworks into their professional identity. Approximately twenty percent of participants did experience some tension between academic education and real-world practice but those social workers with longer experience in the field felt more confident in their interventions and decision-making. The study underscores the universal applicability of social work values and professional processes and how they transcend cultural circumstances and world views. This research contributes to a deeper understanding of how non-western cultural and religious values intersect with Western social work-oriented education in a manner which leads to a selection of interventions by social workers which adhere to principles of competent practice. At the same time these values are deeply rooted in the culture of the society in which they are practiced and are adapted to fit within context specific agency policies. The findings provide a basis for curriculum enhancements that support culturally competent practice in Saudi Arabia and similar settings.20 0Item Restricted The Impact of Supervisor Incivility on Subordinates’ Thriving at Work: The Role of Psychological Capital and Competitive Psychological Climate(Saudi Digital Library, 2026) ALJURAIBI, MOHAMMED; Almeida, ShamikaBackground: Supervisor incivility is increasingly prevalent in today's fiercely competitive business landscape. While numerous societies adhere to a general norm of civility, not all organisations or organisational members may share a uniform perspective regarding demonstrating respect for one another in the workplace. There may be increased supervisor incivility within organisations, as these supervisors can implement the strategies necessary for business success. This raises important questions about the implications of supervisor incivility for employees' mental health and job performance. This study specifically focuses on those employees who have experienced and witnessed incivility from their supervisors. Research suggests that supervisors' behaviour can influence employees' wellbeing. This study focuses on thriving at work, representing a more active state than wellbeing, emphasising continuous growth and learning. Wellbeing emphasises comfort and stability while thriving concerns adaptation and progress. This concept is especially relevant in competitive environments, where maintaining motivation and productivity involves feeling connected to growth and development and not just avoiding burnout. While existing literature has acknowledged the impact of supervisors on employees' wellbeing, there remains a gap in understanding how supervisor incivility— especially witnessed—affects employees' ability to thrive at work. Aim: The study examines the relationship between supervisor incivility and employee thriving at work. The study addresses three research objectives. First, it seeks to determine the differences among the types of supervisor incivility. Second, it examines the effect of supervisor incivility (experienced and witnessed) on employees thriving at work. Third, it seeks to investigate the indirect influence of the two types of supervisor incivility on subordinates' thriving at work through Psychological Capital (PsyCap) (mediator), with Competitive Psychological Climate (CPC) (moderator) as the boundary condition. The study utilises the Transactional Theory of Stress (TTS) to understand how individuals appraise and respond to workplace challenges and Social Learning Theory (SLT) to provide insight into how employees adopt behaviours based on observed interactions, underpinning the effects of managerial behaviours on employee thriving. Method: A mixed methods approach is used to collect and analyse the data, including surveys and interviews. Using an online survey approach in the main study, Phase One, data were gathered from 412 Junior Medical Officers (JMOs) in Saudi Arabia and analysed using the Statistical Package for Social Sciences (SPSS), regression, and PROCESS macro. Using the interview approach in Phase Two, data were gathered from 25 JMOs and analysed using thematic analysis to comprehend the findings of Phase One. Results: Phase one of the study showed that the levels of PsyCap and the thriving of subordinates vary in line with the type of supervisor incivility in increasingly competitive and pressured workplace environments. Specifically, the findings show that supervisor incivility affects employees' PsyCap. Further, the indirect effect of supervisor incivility on thriving at work through PsyCap is weaker when the CPC is low and stronger when it is high. In a highly competitive work environment, experiencing supervisor incivility results in lower PsyCap. However, it weakened the relationship between witnessed supervisor incivility and PsyCap. Hence, a subordinate appraised witnessing supervisor incivility as a challenge, increasing PsyCap and, in turn, thriving at work. Phase Two of the study explored why subordinates considered supervisor incivility as a challenge. The main reasons that participants highlighted were fear, personal agendas, desire to be in the in-group with their supervisor and cultural values such as respect. The findings also highlighted how JMOs learnt to adapt to incivility, used negative peer experiences as lessons on what to avoid at work with their supervisors and focused on long-term outcomes. All these mechanisms enabled them to thrive at work. Overall, the results showed that supervisor incivility has a bright side in competitive climates and helps employees thrive at work. Contributions and Implications: This study addresses gaps in the literature on supervisor incivility and how employees in high-stress environments, such as healthcare, appraise and manage uncivil behaviour. The present study contributes to knowledge by identifying coping responses, competitive climate, social process, and psychological capital as possible reinforcements of the supervisor witnessed incivility. As such, the study model can be used to understand the negative and positive findings concerning supervisor incivility. The study also provides a Middle Eastern perspective on the types of incivility and their effects on workplace thriving. Empirically, it examines the dual perspectives of victims and observers, offering new insights into how both experienced and witnessed supervisor incivility impact thriving at work. Theoretical contributions include applying TTS to clarify appraisal processes and conditions under which incivility affects subordinates and using SLT to understand why observed supervisor incivility helps employees thrive at work. Practically, the study guides organisations in creating supportive policies and strategies for enhancing employee thriving. It also gives supervisors insights into how their behaviour influences employee responses, ultimately improving organisational effectiveness.26 0Item Restricted The Role of Self-reference in Initial Lexical Acquisition(Saudi Digital Library, 2026) Qahl, Taghreed; Lambert, CraigThis hybrid-model thesis aims to address three questions: (1) How do the four self-referential processing (self, intimate, familiar, and semantic) impact item and source memory for novel L2 lexical items? (2) Do emotional valence and self-referential processing interact with respect to item and source memory? (3) Do self-esteem and self-referential processing interact with respect to item and source memory? Three studies were conducted in response to each question: Study 1: Personal Investment in Language Processing: The Role of Self-Reference in Initial Lexical Acquisition This study investigates the role of self-reference in the initial stages of second language (L2) lexical acquisition. The study is motivated by recent trends in second language acquisition (SLA) research that highlight the positive effects for treatments that draw on learners’ background experiences (e.g., Boudreau et al., 2018; Lambert et al., 2017; Lambert et al., 2023b; Lambert & Zhang, 2019; MacIntyre & Wang, 2021; Stranger-Johannessen & Norton, 2017, 2019). However, the role of the learner in SLA remains undertheorized (Swain, 2013; Lambert, 2023), and further work is needed to identify the specific mechanisms responsible for documented effects and their role in language processing. One such mechanism might be self-reference, which refers to information processed with reference to the self that is typically better remembered than information processed with reference to others (Hamami et al., 2011; Leshikar et al., 2015; Symons & Johnson, 1997). Accordingly, the present study investigates the impact of self-reference on the establishment of form-to-meaning connections during the initial acquisition of L2 lexis in item memory (the meaning of each item) and source memory (the conditions under which the items were processed). 144 Saudi female undergraduate English as a Foreign Language (EFL) learners processed 20 novel L2 trait adjectives counterbalanced across four processing conditions in which they considered each trait with reference to themselves, an intimate other, a familiar other, or a known lexical item. Findings revealed that information processed under personal investment conditions (self-reference and intimate-other reference) was recalled significantly better than information processed under non-personal investment conditions (familiar-other and semantic reference) in both item and source memory. Overall, low-proficiency EFL learners recalled more information when it was personally relevant. Study 2: Emotional Valence, Personal Investment and Initial L2 Lexical Acquisition This study examines the effect of emotional valence in memory for L2 lexical items in interaction with self-referential processing. The study employed a repeated measures design in which the participants processed 20 novel L2 trait adjectives (10 positively and 10 negatively valenced). Lexical items were counterbalanced across conditions and participants, with each lexical item occurring an equal number of times in each condition to control for the effects of specific lexical items. The study reveals that participants recalled negative emotional valence words processed in the personal investment conditions significantly better than in the non-personal investment conditions. Study 3: Domain-Specific Self-Esteem, Personal Investment, and Initial L2 Lexical Acquisition This study investigates self-esteem in memory for novel lexis in interaction with self-reference. Learners evaluated their self-esteem at the time each item was processed. They later recalled the meaning of each item (item memory) and the conditions under which they processed it (source memory). Results revealed that self-esteem interacted significantly with processing condition, in which learners with high self-esteem recalled items processed in the personal investment conditions significantly better than in the non-personal investment conditions in terms of both item and source memory. Personal investment and self-esteem thus had synergistic effects. The thesis contributes to illuminating processes underlying personal investment theory as a basis for research on the role of the learner in second language acquisition (SLA). It also provides insight into how affective factors influence the establishment of initial form-to-meaning relationships in novel L2 lexical acquisition.27 0Item Restricted Exploring the Properties and Stabilisation of Nanoscale Metal Cluster/Overlayer Architectures(Saudi Digital Library, 2026) Asiri, Mohammed; Ebendorff-Heidepriem, HeikeThe shift from fossil fuels to renewable energy sources is a major focus in the global effort to reduce CO2 emissions, with photocatalytic hydrogen production being a promising approach for harvesting energy from sustainable energy sources. Photocatalysts absorb energy from sunlight to drive the water splitting reaction, producing H2. The deposition of a co-catalyst, such as noble metal clusters, can modify and improve the efficiency of the photocatalyst. Metal clusters, consisting of only a few atoms, have gained attention as co-catalysts due to their unique electronic and catalytic properties. However, maintaining their size and stability is challenging, as they tend to agglomerate into larger particles, losing their unique properties. Another challenge is the occurrence of the back reaction during photocatalysis, when H2 and O2 react to form water on the co-catalyst surface. The back reaction reduces the efficiency of photocatalytic water splitting. Atomic Layer Deposition (ALD) of thin metal oxide overlayers on cluster-modified photocatalysts offers a strategy to stabilise the clusters and suppress the back reaction. The self-limiting nature of ALD allows for deposition of an ultrathin overlayer with a controllable thickness. This thesis investigates how ALD-AlOx overlayers can be used to preserve the integrity of noble metal clusters, particularly Au clusters. It is examined how an ALD-AlOx overlayer grows on the surface of a photocatalyst formed by depositing Au clusters on TiO2 surfaces, as well as the distribution and stability of the clusters on the TiO2 surface before and after the ALD overlayer. The growth of ALD-AlOx overlayers on Au101/TiO2 was investigated as a model photocatalyst system to understand how the overlayer grows on the Au clusters and the TiO2 substrate. The investigation determines the overlayer thickness after applying several ALD cycles on a planar TiO2 substrate. The study demonstrated that the ALD-AlOx resulted in evenly deposited overlayers for the system of Au101/TiO2 with a slight tendency to be thicker on the Au cluster than on the TiO2. The layer thicknesses were found to be 2.0 Å, 3.5 Å, and 5.5 Å for 1, 5, and 10 ALD cycles, respectively. A comprehensive study of the stability of Au9(PPh3)8(NO3)3 deposited onto TiO2 by depositing an ultrathin overlayer of ALD-AlOx at various deposition temperatures, 25 °C, 100 °C, 150 °C, and 200 °C was conducted. It was found that ALD-AlOx stabilised Au9 clusters on the TiO2 surface across various temperatures. Notably, the phosphine ligands desorb during the ALD overcoating process at elevated temperatures, while the Au9 cores remained protected beneath the AlOx overlayer. The ALD-AlOx overlayer on Au metal clusters on TiO2 was studied by a combination of microscopic and spectroscopic techniques. It was revealed that the Au101 clusters were distributed randomly across the entire TiO2 surface. The roughness of the Au101/TiO2 system increases as the Au concentration increases, while ALD overcoating smooths the clusters, as the roughness was found to decrease, indicating a uniform coating on clusters by forming thicker overlayers on interstitial regions between clusters. This work provides an understanding of the role of ALD-AlOx overlayer on the stabilisation of Au metal clusters on TiO2 as a photocatalyst model system, with direct relevance of designing and improving photocatalytic water splitting for green hydrogen production.10 0Item Restricted Identification of groundwater flow patterns and barriers in aquifers(Saudi Digital Library, 2025) Asiri, Mohammed; Shelyag, Sergiy; Miller, TonyThe use of inverse methods has been increasing in hydrology. Numerical methods can help identify groundwater barriers and flow patterns in an aquifer, which can reduce errors when comparing the exact and estimated solutions. This thesis uses the method of characteristics (MOC) to identify transmissivity T in an area of abnormal region. From Darcy’s law for steady-state groundwater flow, we start with a one-dimensional case, which helps us consider what may and may not be in the two-dimensional case. Then we use the 2D case to calculate the stream function and find that the gradient of the stream function is orthogonal to the gradient of the head, and we use this when calculating the stream function everywhere. We use MODFLOW to generate head data for the known distribution T and to estimate T under different inflow examples. MOC gives a stable solution and can help identify the area of low T without requiring smoothness of the T distribution.8 0Item Restricted The Effectiveness of Hybrid Micro-Grid System in Selected Locations in Saudi Arabia(Saudi Digital Library, 2026) ALLHIBI, HAMED; Firoz, AlamThe need for socio-economic development, industrialisation, and lifestyle advancement pro- pels rising energy demand globally. The majority of energy needs are met by fossil fuels (coal, oil, and gas), which emit significant greenhouse gas emissions, degrading the environment and accelerating the global climate impact. The greenhouse gas emission and its impact are more prominent in high energy-consuming nations like the Kingdom of Saudi Arabia, where most power is generated by fossil fuels. Although the country’s 35 million population is largely spread in major cities and towns (83%), a significant population (17%) still lives in rural and remote areas across the vast country (2.15 million square km). The power needs for most of these populations are met not by grid-connected power but by locally generated power (mainly diesel fuel). As a responsible nation, the Kingdom of Saudi Arabia has committed to the Paris Climate Agreement and adopted a plan to reduce fossil fuel use for power by gradually increasing renewable power generation, especially in remote and rural areas. The geographic location of Saudi Arabia offers the opportunity to enhance both solar and wind energy. However, the distribution of renewable energy (solar and wind) is not uniform throughout the country. Hence, the primary objective of this study is to explore the opportunity to harness renewable energy along with other types of energy, emphasising CO2 reduction and cost optimisation. The study is envisioned to develop a mathematical model of a hybrid power generation system incorporating solar, wind, and diesel energy for rural areas. This research aims to study and formulate accurate mathematical models to determine the hybrid microgrid system response for renewable energy location and allocation in rural and urban areas. A mathematical model is presented to design hybrid microgrid system based on the positioning of renewable energy resources besides the traditional resources to plan for the entire area. This new model takes into consideration demand needs and limited resources. The objective of the developed model is to minimise the emission and cost of the system while the demand is covered by using renewable energy. To quantify the power needs of the selected population, two areas along with the popu- lation—one in a rural area (Al-Gahah) and the other in an urban area (Jeddah)—have been selected. Data on household power usage have been obtained and analysed. Wind character- istics and solar irradiation data from the selected areas have also been collected. Based on collected data, the hybrid power generation mathematical model has been developed using five scenarios: a) diesel only, b) diesel and solar, c) diesel and wind, and d) diesel, solar, and wind. Initially, commercial software (HOMER) was used to predict optimal power generation for four scenarios. However, the optimised prediction did not fully address the need for local population requirements, especially the CO2 and cost together. To overcome these limita- tions, the mathematical power generation prediction model has been developed, validated by first an Excel-based model and later a Python-based model. The model validated by the case study data across four distinct scenarios, illustrate the robustness and efficacy of the model. It fulfils all constraints, determining the system configuration that achieves the de- sired function while complying with environmental and financial restrictions. The developed model is capable of predicting optimised power generation incorporating both cost and CO2 emissions. It can also be used to determine optimal power generation based only on cost or CO2 emissions. The model can be used to develop a hybrid power generation system using solar, wind, and other energy for areas in Saudi Arabia and elsewhere. The model can be used to enhance strategic, tactical, and operational planning for hybrid microgrid systems for achieving a more reliable power supply, a cleaner environment through diminished CO2 emis- sions, and reduced operational expenses for diverse microgrid and mini-grid power generation in Saudi Arabia and elsewhere.7 0Item Embargo Three Essays on Corporate Political Donations(Saudi Digital Library, 2026) Aloraini, Ali; Effiezal, Abdul Wahab; Imran, HaiderThis thesis contains three distinct but interconnected essays that examine corporate political donations and their influence on corporate behaviour among Australian publicly listed firms. In response to the ongoing debate concerning the effectiveness and implications of corporate political engagement, the study consists of three essays examining various aspects of corporate political donations to provide valuable insights into this corporate activity. The thesis attempts to determine whether firms making political donations are engaging in harmful agency behaviour or such donations serve as strategic tools for advancing legitimate business interests through stakeholder relationship management and regulatory engagement. Using datasets covering the period from 2006 to 2022 with 2,973 to 3,404 firm-year observations, the first essay examines corporate outcomes and reports that firms making political donations exhibit lower levels of cash holdings, higher leverage, and reduced investment efficiency. The second essay investigates earnings quality and reveals that political donations are associated with higher levels of earnings quality across multiple earnings management proxies. The third essay explores tax behaviour and indicates that politically active firms engage in more conservative tax planning rather than aggressive tax-avoidance strategies. These findings highlight competing theoretical explanations for corporate political engagement. The first essay supports agency theory concerns, suggesting that political donations reflect managerial opportunism that harms shareholder value. In contrast, the second and third essays validate legitimacy theory by suggesting that politically active firms, seeking to maintain societal approval and regulatory favour, improve their reporting quality and adopt responsible tax practices. Consequently, this thesis reveals a complex duality in corporate political engagement, where agency costs collaborate with legitimacy benefits. While political donations may lead to suboptimal financial decision-making, they also contribute to enhanced earnings quality and prudent tax behaviour. Firms and investors should therefore consider both potential agency issues and legitimacy advantages when evaluating corporate political activities. The first chapter provides the introduction to the thesis, discussing its motivation and structure, and offering an overall background on political connections. The second chapter explores the relationship between political donations and corporate outcomes, including cash holdings, leverage, and investment efficiency. The analysis examines multiple political donation measures and conducts additional tests, including endogeneity tests, to ensure reliable results. The third chapter investigates the association between political donations and earnings quality using multiple measures of earnings management. This study employs various political donation and earnings quality measures and performs additional tests, and endogeneity checks to verify the main findings. The fourth chapter analyses the link between political donations and tax avoidance, using different measures of political donations and tax avoidance, and conducting further robustness tests. Finally, the fifth chapter documents the major conclusions, discusses the limitations of the thesis, and outlines suggestions for future research.12 0Item Restricted Detection and Quantification of Nicotine and Other Volatile Compounds in E-Cigarettes Using Gas Chromatography-Mass Spectrometry(Saudi Digital Library, 2025) Alzahrani, Amjad; Dayanne, MozanerElectronic cigarettes (e-cigarettes) are popular nicotine delivery systems, but their labeled nicotine content is often unregulated and potentially inaccurate posing a risk to consum ers. The purpose of this experiment was to develop and validate a Gas Chromatography-Mass Spectrometry (GC-MS) method to quantify the amount of nicotine in a disposable e-cigarette (IGET XXL) advertised as containing 5.0% nicotine. A direct weighing method was employed wherein 0.0716 g of e-liquid was dissolved in methanol within a 10 mL volumetric flask subse quently undergoing a 1-in-10 serial dilution. Quinoline was added as an internal standard and samples were analyzed by GC-MS in selected Ion monitoring (SIM) mode against a six point (0.5 25.0 mg/L) calibration curve. The method was validated demonstrating excellent linearity (R² = 0.9955) accuracy (98.5% recovery of a 10.0 mg/L QC standard) and precision (1.65% RSD). The primary finding was a measured nicotine concentration of 7.56 mg/g (0.757% w/w). This meas ured concentration is approximately 6 times lower than the 5.0% w/v (50 mg/mL) claimed on the product packaging representing only 16.7% of the advertised strength. These findings confirm a significant discrepancy between the labeled and actual nicotine content highlighting potential quality control issues in the e-cigarette market. This study demonstrates that the validated GC MS method is an effective and reliable tool for the independent chemical verification of such con sumer products.55 0Item Restricted The Effectiveness of Hybrid Micro-Grid System in Selected Locations in Saudi Arabia(Saudi Digital Library, 2026) ALLHIBI, HAMED; Alam, FirozThe need for socio-economic development, industrialisation, and lifestyle advancement propels rising energy demand globally. The majority of energy needs are met by fossil fuels (coal, oil, and gas), which emit significant greenhouse gas emissions, degrading the environment and accelerating the global climate impact. The greenhouse gas emission and its impact are more prominent in high energy-consuming nations like the Kingdom of Saudi Arabia, where most power is generated by fossil fuels. Although the country’s 35 million population is largely spread in major cities and towns (83%), a significant population (17%) still lives in rural and remote areas across the vast country (2.15 million square km). The power needs for most of these populations are met not by grid-connected power but by locally generated power (mainly diesel fuel). As a responsible nation, the Kingdom of Saudi Arabia has committed to the Paris Climate Agreement and adopted a plan to reduce fossil fuel use for power by gradually increasing renewable power generation, especially in remote and rural areas. The geographic location of Saudi Arabia offers the opportunity to enhance both solar and wind energy. However, the distribution of renewable energy (solar and wind) is not uniform throughout the country. Hence, the primary objective of this study is to explore the opportunity to harness renewable energy along with other types of energy, emphasising CO2 reduction and cost optimisation. The study is envisioned to develop a mathematical model of a hybrid power generation system incorporating solar, wind, and diesel energy for rural areas. This research aims to study and formulate accurate mathematical models to determine the hybrid microgrid system response for renewable energy location and allocation in rural and urban areas. A mathematical model is presented to design hybrid microgrid system based on the positioning of renewable energy resources besides the traditional resources to plan for the entire area. This new model takes into consideration demand needs and limited resources. The objective of the developed model is to minimise the emission and cost of the system while the demand is covered by using renewable energy. To quantify the power needs of the selected population, two areas along with the population— one in a rural area (Al-Gahah) and the other in an urban area (Jeddah)—have been selected. Data on household power usage have been obtained and analysed. Wind characteristics and solar irradiation data from the selected areas have also been collected. Based on collected data, the hybrid power generation mathematical model has been developed using five scenarios: a) diesel only, b) diesel and solar, c) diesel and wind, and d) diesel, solar, and wind. Initially, commercial software (HOMER) was used to predict optimal power generation for four scenarios. However, the optimised prediction did not fully address the need for local population requirements, especially the CO2 and cost together. To overcome these limitations, the mathematical power generation prediction model has been developed, validated by first an Excel-based model and later a Python-based model. The model validated by the case study data across four distinct scenarios, illustrate the robustness and efficacy of the model. It fulfils all constraints, determining the system configuration that achieves the desired function while complying with environmental and financial restrictions. The developed model is capable of predicting optimised power generation incorporating both cost and CO2 emissions. It can also be used to determine optimal power generation based only on cost or CO2 emissions. The model can be used to develop a hybrid power generation system using solar, wind, and other energy for areas in Saudi Arabia and elsewhere. The model can be used to enhance strategic, tactical, and operational planning for hybrid microgrid systems for achieving a more reliable power supply, a cleaner environment through diminished CO2 emissions, and reduced operational expenses for diverse microgrid and mini-grid power generation in Saudi Arabia and elsewhere.11 0Item Restricted Delineating the role of E-selectin in vincristine-induced peripheral neuropathy(Saudi Digital Library, 2025) ِِAlshammari, Ammar; Vetter, IrinaChemotherapy-induced peripheral neuropathy (CIPN) is a prevalent and debilitating adverse effect of cancer treatment, affecting a substantial proportion of patients undergoing chemotherapy. Vincristine, a widely used drug in the treatment of haematological and brain malignancies, is particularly associated with high rates of neuropathy, especially in children. The resulting sensory, motor and autonomic disturbances substantially impair patient quality of life and frequently necessitate dose reduction or discontinuation of chemotherapy, thereby compromising treatment outcomes. Despite its prevalence and impact, vincristine-induced peripheral neuropathy (VIPN) remains without effective preventive or therapeutic strategies, largely due to limited understanding of the underlying mechanisms. Traditionally, VIPN has been regarded as a neuron-centric disorder, arising from direct neurotoxicity caused by disruption of microtubule dynamics and axonal transport. More recent work, however, highlights the importance of neuroimmune and neurovascular mechanisms. In particular, immune cell infiltration into dorsal root ganglia (DRG) and peripheral nerves, coupled with activation of inflammatory pathways such as the NLRP3 inflammasome, have emerged as a key driver of this condition. Endothelial adhesion molecules are increasingly recognised as upstream regulators of these processes, orchestrating leukocyte recruitment across the blood–nerve barrier. Interestingly, preliminary data from our laboratory demonstrated that genetic deletion of endothelial E-selectin, an inducible adhesion molecule, abolishes VIPN in mice, strongly implicating E-selectin in macrophage-driven neuroinflammation. The present thesis was therefore designed to delineate the role of E-selectin in VIPN pathogenesis, with a particular focus on its contribution to immune cell recruitment, activation and the development of hypersensitivity. Accordingly, I employed a set of complementary studies spanning methodological development, functional testing and mechanistic investigation. First, a reproducible method for DRG immunohistochemistry was optimised, enabling accurate quantification of immune cell accumulation and supporting subsequent mechanistic investigations (Chapter 2). Then, blocking antibodies and knockout models revealed E-selectin as a key mediator of vincristine-induced hypersensitivity and macrophage accumulation at peripheral nerves (Chapter 3). Building on this, a novel intraplantar E-selectin injection model demonstrated that local administration of recombinant E-selectin was sufficient to induce macrophage-dependent allodynia, providing direct evidence that E-selectin initiates pro-nociceptive immune responses in vivo (Chapter 4). Finally, mechanistic studies showed that E-selectin engagement promotes macrophage adhesion, potentiates NLRP3 inflammasome activation and increases interleukin-1β (IL-1β) release (Chapter 5). Collectively, the findings presented here establish E-selectin as a previously unrecognised driver of vincristine-induced neuroinflammation. Rather than acting solely as an adhesion molecule, E-selectin is shown to orchestrate macrophage recruitment while simultaneously amplifying their pro-inflammatory activity, thereby linking vascular activation to nociceptor sensitisation. This work therefore reframes VIPN as not only a consequence of direct axonal toxicity, but also as a pathology rooted in endothelial–immune interactions and provides the first mechanistic evidence that E-selectin contributes directly to its development. More broadly, this work highlights E-selectin as a novel regulator of endothelial–immune communication in the peripheral nervous system. While the studies herein focus on VIPN, the implications extend to other neuropathic conditions in which macrophage recruitment and vascular activation are implicated. Importantly, the identification of E-selectin as a mechanistic driver of macrophage-mediated hypersensitivity provides a foundation for future studies to explore context-dependent roles of E-selectin and assess the therapeutic potential of targeting E-selectin in neuropathic pain.16 0