Towards an enhanced understanding of suicide risk through the lens of the Integrated Motivational-Volitional (IMV) Model of Suicide

Background and Aims: This thesis investigates the complex interplay of a range of psychological factors implicated in suicide risk, including multidimensional perfectionism, childhood trauma, and self-discrepancies within the context of the Integrated Motivational-Volitional Model (IMV) of Suicide. Although perfectionism, defined as striving for flawlessness and setting exceedingly high standards while being concerned about others’ evaluations, has been linked to suicide risk, the mechanisms and contextual factors underlying this relationship still require further investigation. It is also worth investigating the extent to which childhood trauma and self-discrepancies relate to established correlates of suicide risk, such as defeat and entrapment, within the IMV model’s framework. Therefore, this thesis set out to address these gaps by considering perfectionism, childhood trauma and self-discrepancies as pre-motivational risk factors. In addition, it aims to systematically explore the moderators and mediators of perfectionism (as a pre-motivational risk factor) and suicide risk relationship. Finally, by integrating Self-Discrepancy Theory within the IMV model’s framework, this research aims to better understand how different cognitive appraisals are associated with suicidal ideation. Methods: This thesis consists of a series of studies that combine a systematic review (41 studies) and three empirical studies (N=579, N=579, N=529 participants, respectively). The systematic review searched nine databases, and it had the specific aim of identifying the mediators and moderators of the relationship between perfectionism and suicide risk. Building upon the systematic review, three empirical online studies with cross-sectional designs were undertaken with UK community-based samples. Multivariate analyses, including regression-based mediation and moderation analyses (utilising Hayes’ PROCESS Macro), were applied to test the pathways and interactions depicted in the IMV model. These analyses focused on the key roles of defeat, fear of humiliation, and internal/external entrapment in the pathway to suicidal ideation. Results: The systematic review (Chapter 2) identified 41 potential mediators and 20 moderators that either elucidate or modify the trajectory from perfectionistic strivings/concerns to suicide risk. In Chapter 3, there was evidence that perfectionistic concerns and childhood trauma were associated with internal and external entrapment directly, and indirectly, via defeat and fear of humiliation. Although defeat emerged as a stronger mediator overall in the relationships of perfectionistic concerns and childhood trauma with internal/external entrapment, fear of humiliation indirect-only mediated relationships of perfectionistic strivings and childhood trauma with external entrapment and partially mediated the relationship between perfectionistic concerns and external entrapment. As expected, ruminative flooding moderated the relationships between defeat, fear of humiliation, and external entrapment, but not internal entrapment. The mediating roles of internal/external entrapment were consistently found to be significant in all the conceptual models in Chapter 4. However, contrary to the hypotheses, the potential moderating roles of goal adjustment factors, thwarted belongingness, and perceived burdensomeness were not significant. Finally, in Chapter 5, aspects of self-discrepancies (actual vs ideal and actual vs ought) were stronger correlates of defeat and internal/external entrapment, and subsequently, suicidal ideation directly and indirectly compared to perfectionistic concerns. Again, defeat and internal/external entrapment acted as significant mediators in all of the conceptual models, consistent with the IMV model. Conclusions: Overall, the studies provided robust empirical support for the central components of the IMV model by elucidating how perfectionism interacts with various cognitive-emotional vulnerabilities to elevate suicide risk. The identification of key mediators, especially defeat and entrapment, and key pre-motivational vulnerabilities, such as self-discrepancies, offers promising additional targets for clinical interventions to prevent suicide risk. This thesis advanced the theoretical understanding of the IMV model and informed future research efforts. Despite several limitations, this research provides a strong foundation for future research exploring cognitive-emotional and pre-motivational vulnerabilities to suicide risk. The integration of the Self-discrepancy Theory into the IMV model’s framework advanced the theoretical understanding of suicide risk, as well as providing robust foundations for future clinical applications and endeavours in the suicide prevention field

Exploring the role of substrate stiffness in endothelial senescence

The last two centuries have witnessed a remarkable rise in average human life expectancy, which has doubled in the most advanced countries. Cardiovascular diseases are among the leading causes of death in older adults. As the proportion of elderly people grows, the number of those affected by some form of cardiovascular disease is expected to continue increasing; hence, narrowing the gap between total and healthy lifespan becomes essential. One of the key hallmarks of ageing is cellular senescence, a stable state of cell cycle arrest. Endothelial cells are among the first to undergo senescence, and tissues with a high density of endothelial cells exhibit the highest levels of senescence. It is now widely recognised that the mechanical properties of the extracellular matrix strongly influence cellular behaviour and that these properties change with ageing. Arterial stiffness progressively increases with age, contributing to a higher risk of cardiovascular diseases. While various studies have explored the role of physical stimuli in senescence, much remains to be uncovered regarding the effect of stiffness on endothelial senescence. We aim to address this gap by studying the role of stiffness on endothelial senescence and exploring the differences in response depending on the senescence inducer. To do so, we worked with human umbilical vein endothelial cells (HUVECs), growing them to monolayer state and inducing senescence either through treatment with the chemotherapeutic drug Doxorubicin or by passaging the cells to mimic therapy-induced senescence and replicative senescence, respectively. To assess senescence induction, we examined various hallmarks, including DNA damage, β-gal staining, cytokine secretion, cell cycle arrest, and proliferation. To evaluate the effect of substrate stiffness on the phenotype, we seeded the cells onto collagen-coated polyacrylamide hydrogels of two different stiffnesses (3 kPa and 30 kPa) as well as glass. Additionally, we analysed cellular morphology and adhesion, nuclear morphology and lamina properties, YAP nuclear translocation, and cell-cell adhesion proteins. Finally, we investigated the mechanical properties of these cells to determine their mechanical fingerprint. In this study, we first established two effective methods for inducing senescence in HUVECs in vitro. For therapy-induced senescence using Doxorubicin, we optimised our protocol by initially testing a wide range of doses. The doses were first narrowed down based on toxicity and then further refined by assessing senescence hallmarks. For replicative senescence (RS), we first evaluated population doubling before performing the senescence assays. Next, we produced and characterised polyacrylamide hydrogels to examine senescence markers as a function of substrate stiffness. Overall, we observed a substantial increase in senescence markers at increasing stiffness. In senescent populations on glass, we detected an increase in cell cycle arrest markers, β-gal staining, DNA damage, and cytokine secretion. RNA sequencing further revealed an upregulation of genes associated with cell-adhesion and leukocyte migration. In Doxorubicin-treated cells, the senescence-associated secretory phenotype (SASP) was more pronounced compared to RS cells, whereas the opposite was observed for p53 and DNA damage. Interestingly, on softer substrates, SASP was significantly reduced in Doxorubicin-treated cells compared to those on stiffer substrates. To further characterise our model, we investigated how mechanosensing and mechanotransductive elements were altered by senescence in endothelial cells. In Doxorubicin-treated cells, we observed an increased aspect ratio and a larger cellular area compared to the control. The nuclear area appeared particularly enlarged, alongside increased YAP nuclear translocation. Regarding the nuclear lamina, lamin A/C invaginations were more pronounced, while lamin B intensity was reduced. Replicative senescent cells exhibited increased cellular area and stiffness. They also displayed a greater number of focal adhesions and reduced VE-cadherin and CD31 intensity. Additionally, they showed increased YAP nuclear translocation, decreased lamin B intensity, and a higher prevalence of lamin B and lamin A/C invaginations. In summary, we propose a system for modelling endothelial senescence using two distinct methods and investigating the impact of substrates’ stiffness on senescence. We successfully modelled senescence and confirmed the detrimental effect of matrix stiffness on the senescent phenotype. Furthermore, we demonstrated that senescence not only affects cellular proliferation but also influences cellular morphology and adhesion, nuclear morphology and lamina properties, cell-cell interactions, and the mechanical fingerprint of cells. We also showed that the level of expression in the senescent markers, as well as the mechanobiology related changes, depend on the senescence inducer. We believe this work provides an insightful overview of the impact of substrate stiffness on endothelial senescence. To the best of our knowledge, it is the first time this type of study compares two different inducers of senescence. We hope the results obtained will enable further research on the complex relationship between arterial stiffening and endothelial senescence, which may eventually help prevent cardiovascular disorders

The synoptic Jesus as God

Abstract not currently available

Characterization of peripheral immune dysregulation and brain neuroimmune pathophysiology in the Df(16)A+/- Mouse Model of 22q11.2 Deletion Syndrome, a high genetic risk factor for schizophrenia

Schizophrenia (SCZ) is a severe and chronic neurodevelopmental disorder that imposes a profound global health burden. Among its complex genetic underpinnings, the 22q11.2 Deletion Syndrome (22q11.2DS) stands out as the highest-known genetic risk factor, with approximately 25-30% of affected individuals developing a psychotic disorder. Recent research in SCZ has undergone a paradigm shift, moving beyond purely neurocentric models to embrace growing evidence that implicates immune dysregulation and neuroinflammation as critical etiological processes. While 22q11.2DS is known to confer a complex immunological phenotype, including foundational T-cell deficits and a high incidence of autoimmune disorders, the functional consequences of this genetic 'first hit' on immune reactivity and central nervous system (CNS) vulnerability is not well understood. Therefore, the primary objective of this thesis was to systematically characterize immune dysregulation in the Df(16)A+/- mouse model of 22q11.2DS to test the hypothesis that the genetic deletion programs a dysfunctional response to subsequent inflammatory challenges, thereby providing a plausible biological substrate for neuropsychiatric risk. This investigation utilized the Df(16)A+/- mouse model, which carries a chromosomal deletion syntenic to the human 22q11.2DS critical region. Our experimental strategy involved a comprehensive profiling of the peripheral and central immune systems at a homeostatic baseline and following provocation with distinct immune stimuli, including a sustained Toll-like receptor 7 (TLR7) agonist (Aldara) and an acute Toll-like receptor 3 (TLR3) agonist (LMW-Poly(I:C)). Given the limited characterization of the Df(16)A+/- immune profile and the incompletely elucidated mechanisms linking 22q11.2DS to psychiatric risk, this thesis employed both hypothesis-driven and exploratory analytical frameworks to systematically characterize the immune phenotype. Primary analytical techniques included multi-plex immunoassays (Luminex), multi-parameter flow cytometry, and quantitative immunohistochemistry. This central analysis was supported by the development of a high-throughput, objective morphometric pipeline to robustly quantify glial reactivity and neuronal cytoarchitecture within the hippocampus. Our results demonstrate that the Df(16)A+/- genotype is not immunologically silent but confers a "first hit" of subtle, multi-system dysregulation. Peripherally, this is defined by a "central deficit, peripheral compensation" model, with foundational T-cell developmental deficits in the bone marrow and thymus that are compensated for in circulating blood and spleen populations. This cellular alteration is mirrored by a rewired baseline molecular milieu, characterized by increased inter-animal heterogeneity and a less interconnected systemic cytokine network. Centrally, this state corresponds to a latent glial vulnerability, defined by a subtle but significant reduction in the morphological complexity of hippocampal microglia, anatomically co-localized to the dorsal CA1 and dentate gyrus. Subsequent immune challenges revealed this vulnerable baseline dictates a "second hit" of a profoundly dysfunctional and uncoupled neuro-immune response. The systemic reaction to the TLR7 challenge was both attenuated in magnitude, with blunted splenomegaly and pro-inflammatory cytokine upregulation, and qualitatively dysregulated, exemplified by the paradoxical downregulation of IFN-alpha and the collapse of the organized inflammatory network. Critically, this peripheral impairment was associated with a complete uncoupling of the glial inflammatory cascade in the dorsal hippocampus: wildtype mice mounted a coordinated neuroinflammatory response, whereas Df(16)A+/- mice exhibited a dissociated cascade where microglia adopted a morphologically reactive state in the complete absence of a canonical astrocyte (GFAP+) response. This microglial response was itself dysfunctional, occurring without the expected upregulation of the functional protein Iba1. This glial uncoupling was directly associated with the neuronal findings: Df(16)A+/- mice exhibited an altered parvalbumin-positive (PV+) interneuron response, lacking the significant change in cell counts observed in wildtype animals following the challenge. Findings from an acute TLR3 challenge, qualified by a severe physiological confound of hypothermia, also pointed towards a rewired inflammatory program by revealing a paradoxical central myeloid response. The central conclusion of this thesis is that the 22q11.2DS-relevant genetic deletion establishes a "first hit" of homeostatic instability that dictates a functionally impaired "second hit" response to immune challenges. This work links this high-impact genetic risk factor to a specific CNS vulnerability, defined by an uncoupled neuroinflammatory cascade, where microglia activate but astrocytes fail to respond, and a corresponding genotype-specific PV+ interneuron response, where the significant change in cell counts seen in wildtype animals was absent in the Df(16)A+/- mice. This integrated phenotype provides a novel and plausible biological substrate for the increased neuropsychiatric risk observed in the human 22q11.2DS population

Design and optimization of transceiver design for semantic communication

Semantic communication (SemCom) has emerged as a transformative paradigm that transmits the meaning of information instead of raw data, offering significant potential to break through the limitations of traditional communication systems. By focusing on semantics, SemCom can dramatically reduce data transmission requirements, enhance communication efficiency, and enable intelligent decision-making in complex environments. Its applications range from terrestrial wireless networks to extraterrestrial missions, where it can significantly reduce communication latency and ensure reliable information exchange. However, the practical deployment of SemCom requires overcoming multiple challenges to ensure its universal applicability and robust performance across diverse scenarios. These challenges can be broadly categorized into two key areas. First, when introducing SemCom within traditional communication frameworks, selecting an appropriate semantic coding model (SCM) remains difficult due to the diversity of source information, user background knowledge (BK), and dynamic channel conditions. Efficiently managing computing resources and bandwidth is also essential, as large-scale semantic coding models consume significant resources. Furthermore, constructing effective background knowledge for reasoning in SemCom is complex, particularly when training data is insufficient or incomplete. Addressing these challenges is critical to achieving the general applicability and reliability of SemCom. Second, SemCom’s potential can be further unlocked in specific engineering applications where its advantages are particularly evident. For example, in autonomous lunar landing missions and UAV/UGV cooperative operations, SemCom’s capability to extract and transmit only the most relevant semantic information becomes essential. However, these scenarios introduce additional obstacles such as channel instability, limited computational capacity, and dynamic communication conditions. Developing tailored SemCom frameworks is necessary to ensure robust performance and reliable communication in these demanding environments. To ensure the reliable and efficient operation of SemCom, my work proposes a series of solutions. First, a Background knowledge Aware SCM SElection (BASE) scheme is developed to tackle the SCM selection problem. BASE leverages graph theory to model relationships between different BKs and employs a deep learning algorithm to predict the performance of semantic coding models. This approach achieves higher information recovery accuracy and improves the likelihood of selecting optimal models compared to traditional methods. Second, a joint computing resource and bandwidth allocation framework is proposed to optimize resource management in SemCom networks. Formulated as a deep reinforcement learning task, this problem is addressed using a multi-agent proximal policy optimization algorithm, which maximizes semantic accuracy under resource-constrained conditions. Third, to enhance the reliability of SemCom transceivers, a GAI-assisted SemCom framework (Gen-SC) is introduced. By utilizing Generative Artificial Intelligence (GAI) to generate high-quality training samples tailored to user contexts, Gen-SC improves the reasoning capabilities of semantic coding models. A discriminator module further ensures that generated samples align with actual data distributions, enabling higher semantic accuracy, especially in scenarios with limited training data. Building on these foundations, the effectiveness of SemCom is demonstrated in challenging application scenarios. For extraterrestrial missions, a novel SemCom framework is designed to support autonomous lunar landing. This framework facilitates the transmission of essential image features from the lander to satellites running remote landing control algorithms. By employing adaptive semantic encoding, it enhances landing accuracy, reduces end-to-end latency, and ensures robust performance in harsh lunar environments. Additionally, a control aware SemCom framework is proposed for UAV and UGV cooperative path planning. Instead of transmitting raw sensory data, this framework extracts and communicates only the critical semantic information relevant to path planning. This approach effectively addresses communication challenges caused by channel fading, interference, and occlusion. The proposed transceiver design ensures accurate and timely coordination between UAVs and UGVs, improving path planning efficiency and mission success rates. Through these contributions, my work advances the understanding and application of SemCom, providing comprehensive solutions for its practical deployment. The proposed methodologies enhance resource efficiency, ensure reliable transceiver operation, and demonstrate robust performance in both terrestrial and extraterrestrial environments. These findings offer valuable insights into the development of intelligent and resilient communication systems for future applications

Substance use, grief, and Scotland’s drug death crisis: exploring lived experiences

Abstract available at each chapter

Impact of doping and interfacial band bending of charge transport layer in inverted perovskite solar cells

This thesis investigates the n-doping reaction mechanism and interfacial band bending of charge transport layers (CTLs) in inverted perovskite solar cells (PSCs). CTLs, comprising electron transport materials (ETMs) and hole transport materials (HTMs), play a crucial role in determining the efficiency of PSCs by facilitating efficient charge extraction and transport while minimising recombination losses. However, device performance is often hindered by challenges such as low intrinsic conductivity of organic ETMs. To address these challenges, this work explores the n-type doping in non-fullerene organic ETMs, with a focus on improving conductivity and studies self-assembled monolayers (SAMs) as HTMs, understanding the influence of fermi levels on high efficiency of inverted PSCs. The study begins by examining functionalized bisflavin (BF) derivatives and naphthalenediimide (NDI) derivatives with glycol and alkyl side-chains as nonfullerene ETMs due to bio-inspired nature and more straightforward synthetic process, compared to conventional ETM such as [6,6]-phenyl-C61-butyric acid methyl ester (PCBM). Due to inherently lower conductivity of these pristine derivatives, n-type doping was performed to enhance the conductivity using the dopant to generate free radical, as confirmed through electron paramagnetic resonance (EPR) measurements. UV-vis absorption spectroscopy and conductivity studies revealed that derivatives with polar glycol side-chains (BFG and NDI-G) facilitated faster doping reactions compared to the non-polar alkyl counterparts (BFA and NDI-EtHx). This behaviour was attributed to the polarity compatibility between the glycol side-chains and the dopant, which promoted molecular interactions and enhanced the doping efficiency. Interestingly, the BF and NDI systems exhibited distinct responses to doping effects. While the doped BF derivatives show limited improvement in charge transport, the doped NDI derivatives demonstrated significant conductivity enhancements. Optimised NDI-G doped materials achieved a conductivity exceeding 10-2 S/cm, resulting in improved photovoltaic performance. Density functional theory (DFT) calculations explained these observations by highlighting the formation of charge transfer complexes (CTCs) with strong binding energies. The alignment of energy levels between CTC and neutral molecules was found to be critical for effective electron transfer and the generation of free charges. Based on these findings, a detailed doping mechanism is proposed in this work. Additionally, bulk defects such as ion vacancies caused the surface recombination in the PSC system, it is necessary to decouple the charge accumulation from recombination. In here, we investigate using a novel stabilization and pulse (SaP) measurement technique to decouple the ionic feature with electronic effect, studying the influence of SAMs on Fermi-level alignment in PSCs. SAMs with varying dipole moments (MeO-2PACz, Me-4PACz, and 2PACz) were studied, revealing distinct flat ion potentials (Vflat) that affected charge extraction efficiency. An optimal Vflat of approximately 0.8 V was identified, while higher values were associated with interfacial barriers and reduced performance. Supporting evidence from Kelvin probe microscopy (KPFM) and time-resolved photoluminescence (TRPL) further confirm this hypothesis. In summary, this thesis contributes insights into the charge transport and recombination through the n-type doping of non-fullerene organic ETMs and the interfacial band bending of SAM-based HTMs in inverted PSCs. The findings underline the strategic importance the doping mechanism and the critical role of interfacial engineering in enhancing photovoltaic performance. These results have broader implications for advancing efficient perovskite-based solar technologies

Douyin short videos and Chinese rural youth: interpreting platformed rural youth cultural production in a shifting rural policy context

This thesis explores the role of Douyin short videos in shaping the cultural production practices of Chinese rural youth within the broader context of shifting rural policies. Since 2018, China has intensified its focus on digital rural development, which, coinciding with the rise of short-video platforms such as Douyin, has provided rural youth with unprecedented opportunities for self-expression, economic advancement, and social engagement. Against this backdrop, this research investigates how rural youth producers (RYPs) create and disseminate digital content; how their cultural production is influenced by national policies and platform mechanisms; and how their engagement with Douyin shapes public perceptions of rural life. The study employs a multi-method qualitative approach, combining digital ethnography, policy analysis, and semi-structured interviews with rural content producers. The findings reveal that rural short videos have transformed the representation of rural China, thereby shifting away from past stereotypes of marginalisation towards more empowered, digitally mediated narratives. However, this process is not solely driven by individual creators: rather, it is shaped by the interplay of state-led rural policies, platform governance, and the economic imperatives of digital labour. The research identifies three key dimensions in this dynamic: (1) the role of rural policies in shaping digital cultural production; (2) the evolving narrative strategies and themes in rural short videos; and (3) the challenges and opportunities faced by rural youth in the digital intermediation process. By situating Douyin’s rural short-video culture within the broader framework of platformisation, digital intermediation, and state governance, this thesis contributes to contemporary discussions on digital labour, rural modernisation, and media regulation in China. It highlights how rural youth, despite structural constraints, are leveraging digital platforms to negotiate their identities, build new economic pathways, and engage in broader socio-political discourses. This research thus offers critical insights into the intersection of technology, policy, and youth culture, positioning rural short-video production as a key site of transformation in China’s digital rural landscape

He Who Pays the Piper Calls the Tune: Exploring asymmetry and imbalance in Scottish Local Government finance since 1974

Abstract not currently available

Calcium-aluminium-rich inclusion populations and abundances within CM chondritic lithologies

Abstract not currently available