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The Shaping of Chinese Primary School YuWen Teachers: Teachers’ Conceptions of YuWen, Narratives of School Environment and Upbringings
No full textYuWen, mainland China’s official first language curriculum, occupies the highest proportion (20–22%) of all compulsory education lessons. However, there is a lack of empirical evidence to show what YuWen means to YuWen teachers. This thesis responds to this gap and asks: how do different Chinese primary school YuWen teachers understand YuWen, and how are individual YuWen teachers’ subjectivities constituted through their narratives about YuWen?
An overarching phenomenological stance provides this research with a conceptual and analytical framework for interpreting teachers’ subjective shaping of YuWen. Specifically, phenomenography is used to reveal the structural features of a group of YuWen teachers’ consciousness by exploring their conceptualisations of YuWen through collective experiences, and phenomenological narrative theory examines the ways in which teachers’ narratives construct their identities.
From 2021 to 2023, three rounds of interviews were conducted. The more phenomenographic informed semi-structured interview questions were used mainly in round 1, and the more narrative approach and biographic questions were used in the following interviews, but the division was not clear-cut. Twenty-one Chinese primary school YuWen teachers from various locations with different lengths of teaching experience, degrees, disciplinary backgrounds and genders were involved in Round 1. Thirteen teachers of those teachers also participated in Round 2, and four teachers were interviewed again in Round 3.
Analysis of the interviews revealed four conceptions of YuWen and how teachers’ narrative constructions of school environments and growing experiences intersected with their conceptions of YuWen. Phenomenographic findings highlighted a non-dualistic perspective in seeing an inseparable relationship between subjective experiences and the objective world, and indicated that teachers’ subjectification can make a difference to the four conceptions of YuWen they held. Their narratives around school environment, upbringing, and authority constructed their subjectivity as YuWen teachers. This thesis brings practitioners’ subjective constructions to the field of YuWen and provides a non-dualistic perspective on language education and teacher education research
The Third Mission, Governance and Higher Education: A Study of the Social Service Mission in Chinese Universities
No full textHigher education (HE)’s role in society has undergone significant transformation in recent decades. The rise of the knowledge economy, neoliberalism, and escalating societal challenges have meant increasing expectations for HE to make broader impacts beyond teaching and research. This shift is evident in the third mission (TM) concept, which encapsulates universities’ contributions across economic, social, sustainable, political and cultural dimensions.
This thesis explores how the TM is conceptualised and operationalised in China, an under-researched context. It focuses on the social service mission (SSM) – China’s indigenous equivalent of the TM – by investigating its portrayal in multilevel policies and its implementation within universities. Adopting a comparative case study approach, it explores how the SSM conforms to or differs from the prevailing Anglophone conceptualisation predominantly derived from Western systems. The study investigates three public universities within China’s stratified system, exemplifying what I term tri-faceted identification of sponsorship, prestige and locationality. University governance, particularly Clark’s (1983) Triangle of Coordination, serves as the main conceptual framework. Qualitative data are principally collected from documentary sources and semi-structured interviews.
This study argues that the SSM in China functions primarily as a state-led policy instrument for achieving multi-level government agendas. The SSM manifests distinct forms, actors, and outcomes, compared to TM’s widespread understanding underpinned by the economic-centric entrepreneurial university framing. This divergence is shaped by China’s centralised HE governance and principal-supervisor-agent governance mechanism. Three case universities operationalise the SSM differently, reflecting varying degrees of state influence corresponding to their three-pronged institutional identities. A notable tension is identified between what I term the dominant state-driven SSM activities, such as technology transfer, and marginal community-oriented initiatives. This study challenges TM’s entrepreneurship-centric conceptualisation, offering contextualised understanding of universities’ evolving functions from non-Western realities. It also raises critical questions about the intersection between universities’ expanding roles and their core academic purposes
The Role of Hippocampal Endothelin B Receptors in Amyloid-β-Induced Neuroinflammation using Mouse and Patient-Derived iPSC Models of Alzheimer’s disease
No full textBACKGROUND:
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, synaptic loss, and the accumulation of amyloid-beta (Aβ) plaques. Growing evidence suggests that neuroinflammation, particularly reactive astrocytes, plays a crucial role in AD progression and may precede Aβ deposition. Endothelin-1 (ET-1), a proinflammatory peptide, is elevated in AD and linked to neuroinflammation through its interaction with endothelin B receptors (ETBR), which are predominantly expressed in astrocytes. ETBR promotes astrocyte reactivity and inflammatory cytokine production. Moreover, excitatory and inhibitory neurons play an essential role in modulating astrocyte function and neuroinflammation. Thus, understanding the interaction between these neuronal subtypes and ETBR signaling in AD could provide valuable insights into disease mechanisms and potential therapeutic targets. I hypothesize that targeting ETBR could offer a promising strategy to modulate neuroinflammation and mitigate AD pathology.
METHOD:
Using cell biology and neuroanatomical procedures combined with confocal microscopy, we investigated changes in the ETBR system during the progression of AD. To assess whether AD-driven neuroinflammation could be modulated, we conducted pharmacological manipulations with the ETBR agonist IRL-1620 and antagonist IRL-2500. These experiments were performed using brain slices of APPNL-F/NL-F mouse model of AD and age-matched to wild-type littermates (12–16 months), as well as post-mortem brain tissue confirmed cases of AD patients and their control counterparts. Furthermore, human induced pluripotent stem cells (hiPSCs) carrying the APP V717I mutation along with isogenic controls were differentiated into excitatory neurons, astrocytes, parvalbumin (PV)- and somatostatin (SST)-expressing interneurons.
RESULTS:
Our study revealed a significant upregulation of ETBR expression in astrocytes of APPNL-F/NL-F mouse models, particularly within the hippocampal CA1 region. Colocalization analysis demonstrated increased overlap between ETBR and SOX9+/GFAP+ reactive astrocytes that correlated with AD neuroinflammation. This pattern was consistently observed in post-mortem AD brain tissue, where ETBR colocalization with astrocytes was markedly higher than in mouse models. The hypertrophic morphology of GFAP-expressing astrocytes across these systems further corroborated the involvement of ETBR in astrocyte activation.In APPNL-F/NL-F mouse models, 7-day in vivo pharmacological modulation showed distinct outcomes that ETBR antagonism significantly reduced both reactive astrocytes and amyloid-associated neuroinflammation in brain slices, whereas ETBR agonism exacerbated astrocyte activation, the expression of GFAP highly increased compared to vehicle controls. These anti-inflammatory effects were replicated in iPSC models following 24-hour in vitro pharmacological modulation, with ETBR antagonism suppressing reactive phenotypes and agonism conversely inducing astrocytic hyperactivation.
CONCLUSION:
Our findings suggest that ETBR expression is significantly upregulated in astrocytes in AD models, contributing to neuroinflammation and disease progression. Pharmacological antagonism of ETBR effectively reduces reactive astrocytes and amyloid-associated neuroinflammation, highlighting ETBR antagonism as a potential therapeutic strategy for AD. Furthermore, the role of excitatory and inhibitory neurons in modulating astrocyte function and neuroinflammation underscores the importance of studying these neuronal subtypes in the context of AD pathology
The Government as Shareholder: The Effects of Public Ownership on Corporate Governance, Sustainability and Service Quality
No full textHow does public ownership affect corporate performance? Due to the significant heterogeneity that exists within ownership models, the answer to this question may vary depending on different performance dimensions and factors that affect the incentives of public and private actors. In three empirical chapters, this thesis examines the impact of various manifestations of public ownership on corporate governance, environmental sustainability and public service quality. The first chapter examines whether different state-owned enterprises (SOEs) legal structures can moderate the levels of political interference, measured as the CEO turnover sensitivity to political change. I find that, while CEOs are more likely to be replaced following a change in government, the turnover-political change sensitivity is weaker when the boards of directors’ independence increases and when SOEs are controlled by a single shareholding entity. The second chapter examines the differences in environmental performance between publicly and privately owned multinational firms by comparing their CO2 emissions in domestic and foreign operations. I find that state ownership is positively associated with domestic environmental performance, at least in high-income countries. However, this association disappears in their foreign operations, where there are no significant differences between public and private firms. The third chapter examines whether service quality varies among water utilities operating under two different privatization models: concessions (private management-public ownership) and asset selling (private management-private ownership). I find that: 1) user-related quality aspects are worse when private management is accompanied by private ownership; 2) asset selling and concessions do not have relevant differences in the case of contractable and asset-related quality dimensions; and 3) asset selling is not associated with better performance for uncontracted asset-related quality dimensions. By integrating insights from the literature on corporate governance, political economy and public administration, this thesis provides a nuanced analysis of the merits and demerits of public and private ownership
Investigating the role of optical coherence tomography and angiography as a disease biomarker in Multiple Sclerosis
No full textThis thesis explores the roles of Optical coherence tomography (OCT) and OCT
angiography (OCTA) as a biomarker in Multiple Sclerosis (MS) within an evolving
field that increasingly prioritises a pathobiological disease definition. There remains a
pressing need for convenient, cost-effective biomarkers with clinical relevance.
Whilst magnetic resonance imaging (MRI) is widely regarded as the gold standard, it
is costly, and volumetric data is not easily reproducible in routine clinical practice.
I initially investigated the utility of OCT and visual biomarkers in predicting long-term
disease progression in patients 15 years after a first demyelinating event. I found
that colour vision was more impaired in non-optic neuritis eyes of patients who
progressed to MS, compared to those who remained clinically isolated, and this
impairment correlated with thinner peripapillary retinal nerve fibre layer (pRNFL) and
macular ganglion cell inner plexiform layer (mGCIPL) on OCT and a higher lesion
burden on MRI.
Then I explored the existing evidence for OCTA as a surrogate for brain
hypoperfusion in MS and its role as an evolving biomarker. This involved validating
the methodology through quality control standards (OSCAR-MP) and assessing
test–retest repeatability and reliability.
I then conducted a cross-sectional analysis within a prospective cohort of adult and
paediatric MS patients (POINT-MS cohort) to explore mechanisms of brain damage
using OCTA. This revealed distinct associations between OCTA metrics and regional
brain volume loss, which differ from those observed with OCT. In adults, OCTA
measures were also associated with visual function and Expanded disability status
scale (EDSS) scores, with stronger correlations seen in early disease. In paediatric
patients, neuroplasticity may contribute to a structural–functional mismatch, resulting
in weaker associations between OCT/OCTA measures and both visual outcomes
and EDSS. However, correlations persisted between OCTA metrics and higher-order
visual association MRI volumes. These findings highlight OCTA’s complementary
role to OCT in revealing links between neurodegeneration, central nervous system
hypoperfusion, and inflammation across ages
Development of Transition Metal Oxides as Next Generation Anode Materials for Potassium-Ion Batteries
No full textRechargeable ion batteries are a vital technology of the modern world, with batteries using lithium ions (LIBs) as the charge carriers being of particular importance. However, lithium has a relatively low crustal abundance and limited global distribution, so the development of alternative rechargeable ion batteries is imperative. One promising ion battery chemistry is potassium based, with the K+ ion as the charge carrier. For the negative electrode, transition oxide-based materials are very promising in high-performance applications, where rapid charge and discharge are essential. Below is a short overview of the three projects included in this thesis. KTiNbO5 (KTNO) has been demonstrated as a promising negative electrode material for lithium and sodium-ion batteries (LIBs and NIBs) but has not been reported in detail for KIBs. By synthesizing solvothermally in the presence of rGO, a KTNO/rGO nanocomposite was created that showed enhanced performance compared to pristine KTNO. The charge storage mechanism of the materials was investigated, indicating that the material was a low-strain, intrinsic pseudocapacitive material. While KTNO exhibits promising performance, it remains far behind graphite, particularly at low rates. By replacing the K+ in the interlayer spacing with Ni2+ through a facile ion-exchange, the performance could be boosted by 240 %. The source of the increased electrochemical performance could be attributed to the increase in the interlayer spacing, as well as the additional redox activity of the nickel. Lastly, to demonstrate the potential of potassium-ion batteries as alternatives to LIBs in low-cost uses, a full cell will be optimized with the positive electrode incorporating K2Mn[Fe(CN)6] and the negative electrode comprising of graphite. The full cell was then optimized in terms of N/P ratio and formation protocols. This confirms the feasibility and promise of potassium-ion full cells
Gas-Phase Electrocatalytic CO₂ Reduction on Pd-Embedded UiO-67 Metal-Organic Framework Precatalysts Under Varying Relative Humidity Conditions
No full textElectrocatalytic CO2 reduction (ECO2R) to high-value chemicals is a promising method to upcycle emitted CO2, but it is also a fascinating scientific challenge. Catalyst materials, as well as cell configurations, play a pivotal role in the efficacy and efficiency of the ECO2R reaction, which also dictates reaction pathways and product selectivity. In this work, we employ the isotopological Zr- and Ce-based UiO-67 metal-organic frameworks (MOFs) that contain Pd species in a zero-gap gas diffusion cathode electrode configuration, where the water content, i.e., relative humidity (RH) level, in the CO2 gas stream can be varied. We show that only UiO-67-based MOFs containing Pd embedded in their pores can produce syngas, while the product selectivity can be controlled by varying the RH levels in the gas stream. The pristine MOFs (precatalysts) undergo chemical and structural transformation during the ECO2R reaction, forming the active catalysts toward CO2 electroreduction to syngas. Our work highlights the effect of water content on the selectivity during ECO2R, but also the need for predictive catalyst design for effective electroreduction of CO2 to high-value chemicals
Decreased IL-17-producing TH cells as a diagnostic marker for STAT signaling-related primary immunodeficiencies
No full textBackground: Certain primary immunodeficiencies present with decreased TH17 counts, including signal transducer and activator of transcription 3 (STAT3)- and dedicator of cytokinesis 8 (DOCK8)-linked hyper-IgE syndrome (HIES) and STAT1-linked chronic mucocutaneous candidiasis disease (CMCD). The diagnosis of CMCD and HIES relies on clinical features and molecular genetics. Objective: We sought to evaluate the diagnostic use of TH17% in patients suspected of HIES or CMCD. Methods: A total of 160 patient samples assessed for TH17% at Great Ormond Street Hospital National Health Service Foundation Trust for Children, London, between 2019 and 2022 were included in this cohort. Among them, 94 patients exhibited low TH17% (H17%, 27 (51.92%) harbored pathogenic or likely pathogenic (P/LP) variants in the genes STAT1 (n = 8), STAT3 (n = 12), DOCK8 (n = 6), and autoimmune regulator (AIRE) (n = 1). In contrast, no disease-causing variants in these genes were identified in patients with a normal TH17% (n = 58). From the scoring parameters, elevated IgE levels (P = .0008), pneumonia (P = .0200), and pathological fractures (P = .0622) were associated with a diagnosis of HIES. Conclusions: TH17 measurement demonstrated high sensitivity for detecting P/LP variants of STAT3, DOCK8, or STAT1. Although TH17 measurement is a valuable screening tool for excluding patients with P/LP variants in these genes, molecular genetics remains essential for a definitive diagnosis
Questioning the boundary between pain and suffering
No full textPain and suffering are important to patients, and therefore, their interaction is central to clinical care. It also encompasses issues at the forefront of pain neuroscience, evolution, epidemiology, and treatment development. While Medieval Europe understood pain as a religious problem and Enlightenment theorists framed pain as a social problem, over the past 200 years, we have come to see pain as a medical problem. The medical problem of pain was originally addressed through the diagnosis and treatment of disease, but Pain Medicine has made the causation and treatment of pain a separate focus for research and clinical care. Palliative care reintroduced attention to suffering into the modern hospital. Eric Cassell argued that suffering arises from threats to the person that go beyond threats to the body. His theory of suffering has been criticized for being too focused on patients' narrative and too tied to a nociception-centered notion of pain. In general, modern medicine has promoted a unidirectional linear model of pain causing suffering in the individual patient. However, this model is not consistent with the latest pain neuroscience and is no longer adequate to guide research or clinical care. If we are to finally overcome dualism in pain theory and practice, we must begin by seeing the relationship between pain and suffering as circular rather than linear. Understanding pain and suffering as a unitary construct can advance pain research and clinical practice by providing a new framework for integrating biological, psychological, and social strategies for treating and preventing pain
A first-in-human phase I clinical trial investigating the safety and efficacy of repeat dosing MSCTRAIL cell therapy in addition to chemotherapy and immunotherapy in patients with advanced lung cancer
No full textINTRODUCTION:
Despite recent progress, advanced non-small cell lung cancer (NSCLC) has poor survival outcomes, necessitating the development of novel therapies. TNF-related apoptosis-inducing ligand (TRAIL) selectively induces cancer cell death and can be delivered to tumours by mesenchymal stromal cells (MSCs) due to the cells’ migratory properties. This first-in-human phase I trial assessed safety and dose of umbilical cord-derived MSCs expressing TRAIL (UC-MSCTRAIL) alongside standard NSCLC therapy.
METHODS:
Participants performance status 0-1 with treatment-naïve, inoperable stage IIIB/IV NSCLC received UC-MSCTRAIL infusions with each cycle of chemotherapy and immunotherapy, up to 3 cycles. A dose de-escalation design was used. Exploratory in vitro and in vivo studies further characterised UC-MSCTRAIL properties.
RESULTS:
Six participants enrolled; four received 4×10⁸ cells/infusion (median 5.4×106 cells/kg), and two received 2×10⁸ cells/infusion (median 2.4×106 cells/kg). Early termination occurred due to asymptomatic pulmonary emboli (N=5), which included two patients that were anticoagulated as a protocol amendment with prophylactic low molecular weight heparin (enoxaparin 40mg) and rivaroxaban 20mg, respectively. Exploratory analyses found no clear pro-coagulant or immunogenic mechanisms, though participants receiving UC-MSCTRAIL had elevated inflammatory markers.
CONCLUSION:
This first-in-human study was terminated due to a high incidence of pulmonary emboli. Though exact mechanism remains unclear, UC-MSCTRAIL may have contributed to a pro-inflammatory environment in participants already at elevated risk of thrombosis due to their malignancy. Future MSC-based therapies should incorporate close monitoring for asymptomatic thrombosis and follow a dose escalation design for safety.
SIGNIFICANCE:
First-in-human study of UC-MSCTRAIL in advanced lung cancer was terminated early due to high prevalence of pulmonary embolism. Safety concerns underscore the need for further research which might include dose-escalation design