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A mixed methods study exploring how multidisciplinary teams support people with motor neuron disease to make decisions about gastrostomy placement
Corruption, Deprivation and Economic Development in sub-Saharan Africa
This thesis broadly examines the impact of lived corruption experiences on healthcare deprivation and tax evasion in sub-Saharan Africa (SSA). While Chapter 1 introduces the thesis, Chapter 2 examines how corruption causes healthcare deprivation in 29 SSA countries. Employing the fifth, sixth and seventh waves of the Afrobarometer survey spanning 2011-2018, I find that corruption in the form of bribe payments within the healthcare sector increases healthcare deprivation. Additionally, corruption experienced in sectors outside health such as education, police, public utilities and identification authorities, have adverse spillovers on healthcare deprivation. Furthermore, I show that corruption impacts healthcare deprivation through two key channels: Loss of income and loss of trust in public institutions. Chapter 3 utilises individual-level datasets to explore the effect of people’s lived corruption experiences on their propensity to evade taxes. I show that the likelihood of tax evasion rises by 19–39.5 percentage points for individuals who have paid bribes to government officials in various sectors–health, education, police, public utilities and identification authorities, compared to their counterparts who have never been extorted. Chapter 4 documents the spillover effects of firm-level corruption (unrelated to taxation) on tax evasion decisions, with evidence from 17 SSA economies. Chapter 4 also examines (a) whether and how corruption in tax agencies impacts tax evasion and (b) the key mediating mechanisms through which corruption impact tax evasion among firms. In contrast to the extant literature, I demonstrate that while corruption involving tax authorities rises tax evasion, corruption outside tax authorities (i.e., bribes paid to obtain operating licenses and secure government contracts) has adverse spillovers on tax evasion. The thesis concludes in Chapter 5 outlining key policy implications
Investigating the Mechanobiology of Macrophages: Implications for Inflammatory Bowel Disease
Macrophages are essential cells of the innate immune system, playing a key role in regulating inflammation, tissue repair, and homeostasis. Their behaviour is tightly controlled by various signalling pathways, including mechanical forces that influence their shape, movement, and function. This process, known as mechanotransduction, allows cells to sense and respond to mechanical signals from their environment, converting these signals into biochemical responses that regulate cellular behaviour. Dysregulation of macrophage functions can lead to chronic inflammatory diseases and cancer. Recent studies have shown that mechanical cues, such as extracellular matrix (ECM) stiffness, fluid flow, cell crowding, and topography, modulate macrophage behaviour in various physiological and pathological contexts. However, the effect of ECM stiffness at relevant physiological levels, particularly in inflammation and fibrosis, has not been fully understood. Previous studies have often relied on single or limited marker approaches, which may not capture the full complexity of macrophage polarization.
To address this gap, we conducted a series of experiments aimed at characterizing THP-1 and bone marrow-derived macrophage (BMDM) protocols to ensure proper validation and reproducibility for our study. We then adapted ECM stiffness values, mimicking the conditions seen in inflammatory bowel disease (IBD), representing both normal and inflamed-fibrotic tissue. Experiments were conducted to assess macrophage polarization states in response to varying stiffness levels. Our results reveal that increasing ECM stiffness promotes the expression of YAP and IL-6 in M1 macrophages, driving a shift towards a pro-inflammatory phenotype. In contrast, M2 macrophages exhibited elevated levels of the anti-inflammatory markers CD163 and IL-10, reflecting an adaptive response to softer ECM conditions. Interestingly, M0 macrophages, which are considered to be non-polarized, adopted a hybrid phenotype, expressing both YAP and CD163, underscoring the inherent plasticity of macrophages when subjected to mechanical stress. In primary BMDMs, stiff ECM conditions induced also mixed phenotypes with favoured M1 polarization, as shown by a significant overlap with established M1 gene expression signatures, further emphasizing the role of ECM stiffness in driving pro-inflammatory responses. These findings challenge the traditional binary M1/M2 polarization model, suggesting that macrophage responses to mechanical cues are nuanced and context dependent.
In the second part of this thesis, we investigated the mechanical regulation of the Poly(C)-binding protein 1 (PCBP1) in macrophages and its role in macrophage polarisation. PCBP1 is a multifunctional RNA-binding protein that plays a crucial role in regulating mRNA stability, splicing, and translation. It is also involved in iron metabolism, acting as an iron chaperone, and is involved in DNA damage repair. Our experiments demonstrate that ECM stiffness and cell density regulate PCBP1 subcellular localization in macrophages. In stiff ECM and low-density environments, PCBP1 localises mainly to the nucleus, while in soft ECM and high cell density, it remained cytoplasmic. PCBP1 knockdown increased CD163 expression, suggesting it modulates M2 polarization. Finally, we demonstrate a possible role of PCBP1 in ECM stiffness dependent DNA damage repair, suggesting a novel mechanism of mechanoprotection
Artificial intelligence for ovarian cancer diagnosis from digital pathology slides
Digital pathology is a rapidly growing field, allowing for the development of assistive diagnostic tools. Many tools use artificial intelligence (AI) to automatically provide insights from whole slide images (WSIs), aiming to improve the accuracy, objectivity, and efficiency of the diagnostic process. Research has typically focused on the most common cancers, but less common cancers have received comparatively little attention. We focus on the histological subtyping of ovarian cancer, an essential diagnostic task for determining optimal treatments and prognoses. Through a systematic literature review, we find that previous research has been limited to model prototyping with small homogeneous datasets, with little focus on clinical utility. We perform the most thorough analyses of automated ovarian cancer histological subtyping to date, using the largest training dataset and evaluating models through cross-validation, hold-out testing, external validations, bootstrapping, and hypothesis testing. Analyses are based on attention- based multiple instance learning (ABMIL) with an ImageNet-pretrained ResNet50 backbone, a commonly used WSI classifier. The computational complexity of current AI models is a key limitation, with pathology labs typically not having sufficient hardware for model deployment. We propose an active tissue sampling technique and show that this approach can drastically reduce the computational burden of inference with minimal impact on diagnostic performance. ABMIL analyses tissue at only a single magnification, with high magnifications offering more cellular detail and low magnifications providing broader tissue context. We find that 10x magnification balances the cellular and histoarchitectural details to give the most accurate ovarian cancer subtyping performance, while drastically reducing the computational burden compared to the clinical standard 40x magnification. Recently, histopathology foundation models have promised to revolutionise diagnostic AI. We analyse 14 foundation models and confirm that they give significantly greater performance than previous feature extractors. In ABMIL, tissue patches are treated as independent of each other. We propose a multi-resolution patch graph network to better model spatial context and find this marginally improves performance. The optimal model, a combination of a foundation model and a graph, achieved five-class balanced accuracies of 88%, 99%, and 77% in three validation sets, where our baseline model achieved only 66%, 69%, and 52%, and individual pathologists achieved 74-91% concordance with similarly determined labels. This gives us confidence that AI models could have clinical utility, so future work should focus on the practicalities of implementation and real-world validation
Player performance, salary and survival analysis in the NBA
Professional sports provide an excellent research environment to study all aspects of the employee-employer relationship. In this study, I use data from the National Basketball Association (NBA) to empirically investigate the impact of contractual arrangements on player performance, salary, and survival. First, I explore changes in player performance in the year at which a contract ends (the contract year). Players improve their performance during the contract year, but no consistent performance decline is observed in the year following the end of the contract year. Second, I focus on salary determination. I demonstrate that player performance is an important driver of their salary. In addition, I explore the interaction between contractual arrangements and salary determination and find that contract length and special clauses, such as player/team options to extend the employment relationship, affect the salary. Third, I explore the determinants of player survival in the league. Good performance, especially offensive win shares, increases player longevity. Changing teams allows young or undrafted players to survive longer in the league. Examining the impact of player options on player survival suggests that player options increase the probability of players changing teams but do not increase the probability of player survival. In summary, my findings indicate that the interaction between contractual arrangements and player performance is important in salary determination and survival in professional sports
Characterisation and Modelling of InAs and AlInAsSb Avalanche Photodiodes
For photodetection up to 3.6 µm in low photon conditions, InAs electron avalanche photodiodes (e-APDs) present a low noise and high-speed alternative to other materials. Despite their excellent ionisation characteristics, the gain of InAs APDs is limited by tunnelling, the difficulty growing thick avalanche layers with low doping, and their detectivity is lowered by high dark currents. By better understanding the tunnelling
behaviour within InAs APDs and by developing InAs-based heterostructures using AlInAsSb, this work aims to overcome these challenges.
To investigate the tunnelling and gain in InAs e-APDs, a TCAD model using Sentaurus was developed. Verification against measured PIN and NIP devices showed that the model well simulated the drift-diffusion current at room temperature, band-to-band tunnelling, and avalanche gain of InAs devices. This was used later to find the gain when the tunnelling current reached an assigned current limit, finding that when the gain at this limit exponentially rose with the avalanche width provided that it was fully depleted and could improved by grading the P layer. Mesas with bevelled sidewalls reached this limit earlier due to hotspots, but could be mitigated when using thick NIP devices.
After this, two InAs lattice-matched random alloys of AlInAsSb were characterised to see their effectiveness as an absorption layer in an InAs heterostructure. Measuring a diffusion dominated current density of 0.0358 A/cm2, a responsivity of 1.39 A/W at 2 µm, a background doping of 6.5 × 1014 cm−3, and a lattice mismatch of 6.79 × 10−4 for the best wafer. By comparison, commercially available 2.6 µm extended InGaAs photodiodes have comparable responsivities of 1.27 A/W, but dark current densities nearly two orders of magnitude lower at 5.1 × 10−4 A/cm2. Overall then AlInAsSb was demonstrated as a viable absorber material on InAs. But better surface passivation and wafer growth is still needed for competitive devices due to the significant surface leakage and high dark currents observed in the measurements.
Finally, the total gain M and excess noise F of a novel InAs heterostructure with both an InAs and AlInAsSb avalanche layer was modelled using modified local model equations and an RPL model. If the individual gain and noise of the InAs layer were M1 and F1 respectively and M2 and F2 for the AlInAsSb layer it was realised that when InAs is the first avalanche stage that M = M1M2 and F = 2 + (F2 − 2)/M1. Leading to a low-noise, high-gain 2-stage APD concept that combines the low-noise behaviour of InAs with the higher potential gains of AlInAsSb, removing the need for thick, difficult-to-grow InAs avalanche
layers. Current InAs APDs have reached gains up to 330 while conventional GaSb lattice-matched AlInAsSb avalanche layers have shown k = 0.018 noise behaviour. TCAD simulations in this predict that 2-stage InAs / AlInAsSb APDs can achieve near k = 0 behaviour up to gains of 500
Advancing Transcranial Electrical Stimulation for Personalised Cognitive Enhancement
Transcranial electrical stimulation (tES) demonstrates potential for cognitive enhancement, including improvements in vigilant attention. However, its efficacy across the population is limited by numerous challenges, including inter-individual variability in the electric fields induced by tES and brain-state dependent responses to stimulation.
This thesis first presents a comprehensive literature review critically analysing challenges in non-invasive brain stimulation (NIBS) research, encompassing the principal brain stimulation modalities and sources of variability. Recommendations are presented, including accounting for inter-individual variability, inclusive research practices, improving spatial precision, and the use of multimodal and multi-site stimulation, among others.
Following the literature review, this thesis addresses the challenge of accessible, participant-specific tES dose control through a novel MRI-free approach developed using the largest electric field modelling simulation of its kind. This scalable approach, which utilises readily available demographic and morphological data, significantly reduces peak electric field strength variability across participants compared to fixed-dose stimulation.
Commercial and academic trends within NIBS and tES are analysed to assess the market readiness for the proposed MRI-free tES dosing approach. This includes a systematic search of academic publications across NIBS modalities and of clinical trials utilizing tES. In addition, the current state of the commercial usage of tES and intellectual property challenges are discussed.
This thesis then explores the electrophysiological correlates of vigilant attention during a continuous random-dot motion task, known to measure spatial attention performance. Electroencephalography features associated with arousal, active attentional suppression and off-task thought are identified. Potentially enabling the future development of brain-state dependent stimulation.
Subsequently, a within-subject sham-controlled electroencephalography and transcranial direct current stimulation experiment investigates the effects of transcranial direct current stimulation applied to the right dorsolateral prefrontal cortex on vigilant attention. While no significant effects were observed, the methodological insights of this work are discussed.
Together, the advances presented in this thesis contribute to a multifaceted approach to addressing key challenges in NIBS research. This thesis proposes a scalable approach to personalized tES dosing, insights into the electrophysiological underpinnings of vigilant attention and offers broader NIBS recommendations. Ultimately, these contributions aim to advance translational, accessible, and individualized cognitive enhancement
Sensorless control of single and dual three phase interior permanent magnet synchronous machines with inductance asymmetries
This thesis presents a comprehensive study on the effect of inductance asymmetries, including self-inductance asymmetries and single open phase faults, and their compensation methods, in high-frequency (HF) signal injection (HFSI) sensorless control of single three-phase (STP) and dual three-phase (DTP) interior permanent magnet synchronous machines (IPMSMs).
Inductance asymmetries, caused by manufacturing tolerances and winding faults etc., can introduce harmonic distortions in the estimated rotor position, deteriorating the performance of HFSI sensorless control systems. It is found in this thesis that the self-inductance asymmetries in multiple phases can cause the 2nd- and 4th-order estimated position errors in HFSI sensorless controlled STP- and DTP-IPMSMs. When self-inductance asymmetries in multiple phases exist in both sets of three-phase windings of DTP-IPMSMs, apart from the 2nd- and 4th-order estimated position errors, there will also be a DC offset estimated position error. Besides, the single open phase fault can lead to a 2nd-order estimated position error in the HFSI sensorless controlled DTP-IPMSM system.
Compensation methods are proposed in this thesis to suppress the estimated position error caused by the inductance asymmetries. For the STP-IPMSM with self-inductance asymmetries in multiple phases, this thesis proposes a synchronous reference frame filter-based compensation method and an anti-rotating d-axis signal injection-based method to mitigate the 2nd-order harmonic estimated position errors. Then, for the DTP-IPMSM with one-set self-inductance asymmetries in multiple phases, this thesis proposes a current summation with a ratio-based method to compensate the 2nd-order harmonic estimated position error and an adaptive notch filter (ANF) -based method to compensate both the 2nd- and 4th-order harmonic estimated position errors. For the DTP-IPMSM with two-set self-inductance asymmetries in multiple phases, an Adaline filter-based compensation method is introduced to suppress both the 2nd- and 4th-order harmonic estimated position errors, and a current direct summation-based method is proposed to cancel the DC offset estimated position error. Finally, this thesis explores the effect of the single open phase fault on HFSI sensorless controlled DTP-IPMSMs, where the 2nd-order harmonic estimated position error can destabilise the HFSI sensorless control system. To address this, an ANF-based compensation method and a current summation with a ratio-based compensation method are proposed, offering a fault-tolerant HFSI sensorless control