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The impact of time, polycystic ovarian syndrome and pregnancy in Idiopathic Intracranial Hypertension
Background
Idiopathic intracranial hypertension (IIH) is characterised by elevated intracranial pressure (ICP) predominately affecting women of reproductive age with obesity. Its incidence is rising in line with obesity rates. There are unmet needs to evaluate the longitudinal visual and headache outcomes, identify prognostic factors, and assess the impact of comorbid conditions such as polycystic ovarian syndrome (PCOS) and the event of pregnancy. In addition, this work was undertaken during the coronavirus pandemic which significantly impacted hospital services and naturally forms the introductory chapter to this COVID-era thesis. This thesis was based on the prospective cohort study, IIH: Life, from Birmingham, and maternal health data from the UK Hospital Episodes Statistics dataset.
There was a clear need for a large prospective cohort study to evaluate visual and headache outcomes over time and help identify any prognostic markers. The benefit of this research was to improve the management of IIH patients by identifying the key modifiable risk factors that affect prognosis.
The commonest endocrinopathy in women of reproductive age is PCOS, which is known to affect pregnancy and fertility and prior literature indicates in more prevalent in women with IIH. Therefore, it is important to evaluate the comorbidity of PCOS and whether it impacts outcomes. Fertility and pregnancy may be impacted by shared mechanisms with PCOS including obesity, metabolic profiles and hyperandrogenism, or through alternative pathways. However, the impact of a diagnosis of IIH has not yet been established and warrants further research.
Pregnancy has the potential to impact IIH longitudinal outcomes due to the associated gestational weight gain, hormonal changes, and the limited treatment options. However, the outcomes have been under investigated with only two published studies, and therefore the guidance has often been to avoid pregnancy and avoid active labour. These themes form an important thread within this thesis.
This thesis aimed to assess the impact of time, PCOS, and pregnancy in IIH in order to improve the management of IIH in women of childbearing age.
Findings
Following the first COVID-19 lockdown, a significant impact on the incidence and management of IIH was observed. Amongst the patients seen in our emergency papilloedema clinic, approximately one-third presented with new onset IIH. Additionally, in individuals with previously diagnosed IIH, a majority (58%) experienced weight gain during the lockdown period, with an average increase of 6.2 kg (standard deviation (SD) 4.6). Importantly, this weight gain was found to be statistically associated with a significant worsening of papilloedema (p=0.013). Furthermore, the emergency CSF diversion surgery (shunting) rate rose 4.7-fold compared to the same period in 2019. Most worryingly, 13% of all IIH patients seen in those 2.5 months had surgical interventions with 21% of the new onset IIH group requiring surgery.
The longitudinal prospective cohort study, IIH: Life, included 490 patients with a confirmed IIH diagnosis. The cohort predominantly consisted of females (98%) with a mean body mass index (BMI) of 38 kg/m2. The study revealed that patients with the thickest ocular coherence tomography (OCT) retinal nerve fibre layer (≥400 µm) exhibited the worst visual outcomes. We noted a delayed decline in the visual field and OCT ganglion cell layer after 12 months. Within the medically managed cohort (n = 426), we found that disease duration and change in BMI had the greatest influence on visual outcomes. There was a substantial burden of headache observed, with a daily headache at presentation and a prior migraine history influencing the long-term headache prognosis.
Atypical presentations of IIH, characterized by asymptomatic or with a normal BMI at diagnosis, were uncommon (10%) and rare (3.7%) respectively. In the asymptomatic cohort most patients developed symptoms over the course of their follow up, and the trajectories were similar regardless of the initial presence or absence of symptoms. Although a normal BMI at the baseline visit was associated with worse visual field function, papilloedema measurements were analogous, and long-term outcomes did not significantly differ between the groups.
Comorbid PCOS in IIH was common (20%, 78/398) in our cohort based on the Rotterdam criteria. The presence of PCOS was associated with a 3.2-fold increased risk of self-reported fertility problems and 4.4-fold for requiring medical intervention for pregnancy. However, it was worth noting that comorbid PCOS did not adversely impact long-term vision or headache outcomes in people living with IIH.
Pregnancy in individuals with IIH presented unique challenges and considerations. An IIH diagnosis was associated with an increased risk of pre-eclampsia (5.3-fold) and gestational diabetes (2.7-fold) compared to the general population. Pre-eclampsia was also increased compared to a PCOS population (3-fold), but not gestational diabetes. Furthermore, reduced birth rates and increased caesarean section rates were also observed. In people with IIH who subsequently became pregnant, pregnancy did not adversely affect visual or headache outcomes and was akin to those with IIH that had never had a pregnancy. IIH diagnosed in pregnancy was rare (2%) but associated with greater papilloedema. However, visual field and acuity measurements were comparable to those with established IIH who became pregnant.
Conclusions
People with IIH were adversely affected by the first COVID-19 national lockdown. Overall IIH has been found to be negatively influenced by papilloedema severity, daily headache at presentation and a personal migraine history, but positively improved by weight loss. Whilst it was found there was a 20% comorbid PCOS prevalence and self-reported fertility problems in this IIH cohort; PCOS was not associated with longer-term adverse outcomes. IIH was also shown to impact fertility, preeclampsia risk, gestational diabetes risk and caesarean section rates. IIH outcomes were impacted when IIH was diagnosed in pregnancy but not in those with established IIH who had a subsequent pregnancy. This body of work has furthered the literature with these new findings of adverse maternal health associations, outlined the spectrum of IIH, and highlighted the neutral influence of pregnancy for the majority of women living with IIH
Unpacking the relationship between urban citizenship and integration strategy: a case study of Osaka (Japan) and Birmingham (UK)
This study has sought to unpack the relationship between urban citizenship and integration strategy for migrants in Osaka (Japan) and Birmingham (UK). While migration-driven (super)diversification has been evident in urban space, the mechanism of urban citizenship and its operation in the context of the city’s migrant integration has yet been underexplored. Through policy analysis of the city’s integration-related documents and qualitative analysis of semi-structured interviews with ‘actors’ of urban citizenship – namely, policymakers, city officials, civil society organisations and migrant-led organisations –, this research examines the framework, governance and acts of urban citizenship formulated in the integration strategy in Osaka and Birmingham, cities where old and new migration flows intersect.
This study argues that the nexus between urban citizenship and integration strategy is manifested in the multi-scalar dynamics and interactions between various actors, and the city’s integration strategy can function to affect urban membership, rights and identity of migrant residents. Actors of urban citizenship strategically use networks that extend beyond the city scale while dealing with national policy directions and discourses, which together dimensionalise the implementation of integration strategy and operation of urban citizenship. This captures the ways through which urban citizenship can be ‘co-produced’ by various actors that transcend simple top-down/bottom-up dynamics and therefore offers empirical evidence to respond to the emerging academic question of urban citizenship and migrant integration. Furthermore, by conducting data collection during the COVID-19 pandemic, this study has made a unique contribution to scholarship by exploring the implications of the cities’ responses to the pandemic in the context of urban citizenship
Functional colloids from a lignin-rich bioresidue and their application
This thesis details the extraction and characterisation of a lignin-rich bioresidue from cocoa bean shell (CBS), the formation of particles using antisolvent precipitation, and applications in emulsions and microfluidics. A co-product of the food industry, there is an estimated 600 kt of CBS produced annually. Lignin, an aromatic component of CBS, is of interest to researchers aiming to develop analogues to current consumer goods from sustainable feedstocks, and as a natural source of aromatics has properties of interest such as hydrophobicity and anti-microbial effects. Lignin liberation from biomass typically involves depolymerisation by processes such as bleaching, often produced as a byproduct of commercial processes such as the Kraft paper pulping process termed Kraft lignin, however, this research uses mild acid assisted ethanol extraction. The bioresidue characteristics and co-products were characterised using analysis techniques such as FTIR and GCMS, identifying the presence of molecular surfactant, termed lipid. The extracted bioresidue which contained the lipid fraction (CBS-LC) was processed further to remove molecular surfactant, generating a second ‘lipid removed’ extract (CBS-LR). It was found that hydrodynamic flow-focusing microfluidics was unsuitable for a proposed desorption approach to antisolvent precipitation in water. An alternative continuous process for colloidal lignin-rich particle (CLP) production was generated by setting up a coaxial jet mixing device (CJM). By varying processing conditions to explore the effect of Reynolds number and volumetric flow rate ratio, non-aggregating particles were precipitated with average diameters between 150 and 600 nm. The aqueous dispersions were stable with respect to particle size for at least 14 days, for both types of extract.
The impact of both lipid and co-extractives from the crude bioresidue was assessed by use of CLPs as Pickering particles in emulsion studies. It was found that the emulsions containing crude CLPs were less efficient at stabilising a 1 in 10 sunflower oil-in-water emulsion than Kraft lignin analogues. This was theorised to be the result of the presence of co-extracted molecular surfactant, which may have had a competitive adsorption effect with the CLPs at the oil and water interface. The lipid fraction of the CBS extract was removed, and the resultant change in measured contact angle offered an indication that the CLP surface properties varied from hydrophobic to hydrophilic. It was also found that lignin-rich CLPs could be transferred from aqueous to non-aqueous dispersion in the presence of a molecular surfactant.
The application of the aqueous and non-aqueous CLP dispersions as a particle dispersion for ghost particle velocimetry (GPV) was explored, motivated by the fact that non aqueous tracer particle systems for GPV have not yet been reported. GPV is a technique for flow field imaging introduced in the last 10 years, allowing development of real-time quantification of flow fields in the focal plane and different cross-sections of a microfluidic channel using particles with a diameter of < 200 nm. This is currently achieved using a polystyrene based particle dispersion in the aqueous phase, and by demonstrating that lignin-rich CLPs can equally quantify flow fields, there potential to substitute these, which is an example of waste valorisation and environmentally sustainable substitution of a material. Application examples of this novel particle system were found not only to agree with theoretical flow velocity values but were able to quantify flow simultaneously in static and dynamic flow systems in both aqueous and non-aqueous phases. Whilst this thesis has demonstrated the ability to visualise and quantify flow fields using CLPs, the systems presented contain molecular surfactant in each instance.
This thesis contributes to the understanding of extraction and utilisation of lignin-rich bioresidue from CBS, highlighting its potential for use as a source of colloidal particles. Combining the spectroscopic techniques with characterisations such as contact angle offer insights into how particle behaviour is impacted by composition, paving the way for future advancements in creating dispersed particle systems with potential applicability in flow field imaging. Additionally, the first example of non-aggregating colloidal tracer particles in a non-aqueous system offers great potential for imaging not only the velocity of non-aqueous systems in confined channels, but formation of droplets; an area of significant interest in chemical micro-reactor systems.
To advance research in this area, it is recommended that initial work on the interactions between lignin and co-extracted surfactants are developed with respect to non-aqueous phase dispersions. Furthermore, there is an opportunity to explore the variation of the wetting characteristics of CLPs by employing novel solvent-antisolvent pairings. This would enable greater variation in the polarity of solvents in which CLPs can be dispersed. . In combining modified wettability with the adjustable particle diameter in a CJM, CLPs tailorable in both diameter and wettability may be produced, which could substitute a variety of current food-grade Pickering stabilisers
Investigation of the pressure variation generated by freight train passing through a tunnel
As a train passes through a railway tunnel is creates a series of pressure waves, which travel at the speed of sound within the tunnel environment. These pressure waves not only generate aerodynamic loads on freight train body and tunnel infrastructures, but also have an adverse effect on the comfort of people on the train or within the tunnel as the train passes through. There are a range of methods by which to predict the magnitude of these pressure waves, most notably numerical approaches through 1-dimensional (1d) codes.
The bluff nature of a freight train, coupled with large gaps between wagons and loaded goods, influence the pressure wave pattern generated by it passing through a tunnel. This research addresses the intricate challenges associated with predicting pressure wave patterns caused by freight trains passing through tunnels. The accurate resolution of separation regions at the train nose, within containers, and at unloaded gap sections is essential for precise predictions. Achieving this accuracy demands exceptional mesh quality, significant computational resources, and the careful selection of numerical models. This study evaluates various numerical models to capture these complexities in separation regions. It quantitatively analyses how alterations in train head shape and loading configurations influence resulting pressure patterns within tunnels. These insights are synthesised into an advanced 1d computational framework designed to accurately simulate pressure waves generated by partially loaded freight trains. To achieve these goals, firstly a 1d program is developed, validated against published research, and successfully models pressure wave propagation and reflection. The program's accuracy is further enhanced by integrating a separation bubble model. A comprehensive parameterisation study explores the relationship between train head bluntness, blockage ratio, and separation bubble model parameters. These equations are validated and applied to various train types and tunnel configurations. The programme is extended to consider the discontinuities of the train body by implementing a new mesh system and boundary conditions into the 1d programme, and results are validated against LES data. A parameterisation study for different loading configurations improves program adaptability, and the relationship between predetermined parameters and gap length is investigated. This research bridges the gap in freight train tunnel aerodynamics, offering a versatile 1d computational tool for accurate pressure wave prediction
Can collaborative governance increase community resilience to hazards: A case study from Nepal
This thesis argues for a deeper understanding of the discourse of collaboration, and its influence on emerging collaborative governance regimes in LMIC such as Nepal. Collaborative Governance has become an axiom within disaster risk reduction (DRR) lauded as the best way to reduce risk and increase resilience to hazard; it is a critical part of the United Nations 2030 sustainable development agenda. Yet, despite the recognition CG has there are still questions surrounding the discourse of CG and how it impacts and shapes the governance of DRR. This work utilised a range of approaches from discursive institutionalism to challenge the axiom of CG using Nepal as a case study. Starting with a historical analysis of key policy documents I explore the evolution of collaboration within Nepal’s DRR policy landscape. This work shows how collaboration has emerged through two trajectories, a formal path between the state and international partners such as NGOs and the UN, and an informal path that emerged from the necessity of day-to-day governance needs in remote areas.
These two trajectories are still seen today and influence the narratives that are shaping the current national reforms around DRR. Drawing on semi-structured interviews with DRR actors working at different scales in Nepali DRR, I identify three narratives that are driving a state-sponsored strategy to implement a collaborative governance regime for DRR. These narratives are in line with the international DRR agenda that promotes the local as the primary scale of action. However, my analysis shows that these narratives emphasise top-down state-led goals that risk overlooking the municipal scale government and local communities from meaningful contributions to the emerging collaborative governance regime (CGR) and marginalising local-scale politics. This has resulted in a lack of implementation of key local-scale DRR projects and reforms. Further, I question if the emerging CGR is a truly collaborative and sustainable project.
The tensions that exist between the local and national scale have a marked impact on communities living in remote hazard-prone areas in Nepal, such as the poor implementation of policy reforms including non-functioning community-level DRR groups, unspent DRR funds, and continued lack of access to services. Drawing on interviews taken with community members in Sunkuda this work concludes by exploring the lack of engagement from CG that communities continue to face in Nepal. I argue that alongside the challenges of local scale politics, communities are further overlooked due to the influence resilience of practice in Nepal and its impact has on the emerging CGR. I suggest that to gain a deeper understanding of CG and its potential to reduce risk and increase resilience we need to understand how resilience in Nepal is shaping the emerging CRG in Nepal.
This thesis contributes to scholarship that explores the efficacy of CG to address wicked environmental problems. It calls for more attention to be given to the discursive impact of CG in the fight to increase resilience for remote vulnerable communities in Nepal
The impact of electronic health records on healthcare quality
Background
The NHS is investing significantly in digital transformation, particularly in electronic health records (EHRs), which have rapidly advanced over the past decade. While EHRs are crucial for modernisation, achieving full digital maturity requires substantial investment in teams and approaches to ensure safe and effective use. EHRs have the potential to revolutionise healthcare, yet evidence demonstrating their effectiveness is limited, necessitating rigorous research. Health data can transform healthcare through disease understanding, clinical decision support, service redesign modelling, and policy development, requiring diverse data types. Varying digital maturity across UK health organisations necessitates support for innovation and AI implementation to prevent exacerbating health inequalities.
Methods
The overall methods were the use of real-world health data from the PIONEER Hub for Acute Care to undertake retrospective cohort studies to examine the impact of EHRs on differing aspects of healthcare quality. Synthetically generated EHR and pollution data were generated to enable the implementation and testing of federated analytics.
Results
The retrospective cohort studies presented demonstrate several key findings regarding the impact of EHRs on healthcare. EHRs significantly enhance healthcare quality by streamlining processes, improving accuracy, and supporting evidence-based decision-making. Utilisation of EHR data improves patient outcomes by reducing unnecessary treatments and procedures. The implementation of systems like Computerised Physician Order Entry (CPOE) leads to sustained efficiency improvements in laboratory and clinical processes. Real-World Data (RWD) effectively supports healthcare pathways and policy decisions, though rigorous modelling and testing are necessary to ensure cost-effectiveness. Advancements in data techniques, especially federated analytics, offer innovative solutions to navigating the complexities of health data. These findings underscore the transformative potential of EHRs in healthcare. However, organisations need to ensure consideration is given to the limitations of RWD in respect of quality and cover. Furthermore, with the pace of innovation, especially around AI ensuring that people and organisations with less access to digital tools are not disadvantaged is crucial. Technology should be an enabler to reduce health inequalities, not a reason the divide increases.
Conclusion
In conclusion, EHR data has demonstrated significant potential to enhance healthcare quality. Implementing an EHR can be disruptive to a health care system, but the evidence suggests that staff and patients will benefit in the long-term. The impact has been observed in improved prescribing, efficient pathways and greater accuracy
On endotextuality: literary dystopias, texts-within-texts, and post-truth
This thesis reconceptualises literary works’ additional fictional texts that have long been maligned, dismissed, and overlooked (“endotexts”), devises the theoretical framework that accounts for how they broadly work (“endotextuality”), and explains the specific functions of their different types (“endotextures”). It defines “endotexts” as additional texts that assume the guise of a written document and are only found printed within, alongside, or around a fictional work’s larger main narrative, from whose story-world they originate, and whose thematic concerns and central conceits they metafictionally crystallise, subsequently shaping real-world readers’ interpretations of those narratives and alerting them to the extratextual presence of comparable issues, thus challenging the assumptions of the world that they hold. This definition also addresses “endotextuality”, which brings together transtextuality, the tension between theories of reader-response and the mise en abyme, metafiction, and Barthesian bliss to explicate endotexts’ general aims. Additionally, it establishes three distinct “endotextures”: Written and Read Endotexts, Parallel Endotexts, and Critical Endotexts.
This conceptual work is made in relation to literary dystopias and the phenomenon of post-truth. Twenty-two literary dystopias spanning a one-hundred-and-twelve-year period whose authors represent eleven different nations (Canada, China, the Czech Republic, Egypt, Finland, Germany, Japan, Poland, Russia, the United Kingdom, and the United States of America) have their endotexts analysed in this thesis. This long historical frame of reference and broad geographical span evinces that there is a longstanding tradition of endotextuality within the dystopian genre, whereas the selection of classical, canonical, and contemporary works demonstrates the potential for endotextual readings to uncover new meaning. By conducting these endotextual readings in reference to ideas relating to post-truth, this thesis argues that the dystopian genre possesses a transhistorical, transnational preoccupation with the problem of truth, which subsequently challenges the scholarly assumption that literary dystopias relate only to their specific geohistorical contexts.
This study considers five groups or institutions that literary dystopias – particularly through their endotexts – warn may be responsible for disregarding, distorting, and abusing truth: political leaders, historical experts, the Fourth Estate, digital and social medias, and laypeople. These first four groups represent different arbiters of truth, whereas the final entity represents those arbiters’ typical audience, and so this thesis examines how truth claims are made, by who, and how they are received. Such considerations are therefore peculiarly available to the intensified post-truth condition that has come to characterise the twenty-first century. It sees this thesis propose that dystopian endotexts are uniquely positioned to help readers to resist the pervasiveness and persuasiveness of post-truth, for they challenge the assumptions readers may hold of the world, precisely scrutinise the strategies used to stoke post-truth’s flames, and demand that readers exercise the same degree of active criticality when posed with extratextual truth claims as they do when undertaking the complex interpretive processes engendered by endotexts. As such, this thesis highlights the urgency of dystopian endotexts and the necessity of their new reconceptualization
Recycling and upcycling of cathode materials from lithium-ion batteries
In the past decade there has been a significant increase in the number of electric vehicles (EVs) globally. In turn, this has led to increased amounts of end-of-life (EOL) lithium-ion batteries (LIBs). These EOL LIBs must be recycled to allow the materials from them to be reused. Ideally, closed-loop recycling methods should be used to allow recovered materials to be directly used in the manufacture of materials for new LIBs.
This work investigates recycling of cathode material from a Gen 1 Nissan Leaf which contains a mixture of spinel LiMn2O4 (LMO) and a Ni-rich layered oxide (LO). Both EOL and quality control (QC) rejected material was investigated in this thesis as they are representative of EOL batteries and manufacturing scrap that is likely to be present in the LIB recycling market.
This work develops a method which allows for separation of the LMO and LO phases. Citric acid was employed as a leaching agent to selectively leach the LMO component into solution while leaving the LO phase in the cathode. Citric acid also acts as a delamination agent to remove the remaining LO from the Al current collector. The optimal conditions for allowing facile separation with the best selectivity were 10 mL of 1 M acid at 50 °C with 0.3 g of cathode for 20 mins. The LMO and LO phases were recovered and then utilised in new LIBs. However, LMO is no longer used commercially and has a lower value than Ni/Co containing cathodes therefore this work investigated upcycling it into new cathode materials.
Firstly, LMO was upcycled into Ni-doped spinels. LiMn1.5Ni0.5O4 (LMNO) is attracting commercial interest due its high operating voltage and high energy density. Both EOL and QC LMO were upcycled into LMNO. This work investigates improving the electrochemical performance of upcycled LMNO by changing the composition, synthesis temperature, and synthesis atmosphere. EOL and QC LMNO were shown to have an improved capacity retention compared to pristine LMNO.
This work also investigates upcycling LMO into Mn-containing cation disordered rocksalt (DRS) materials. Firstly, work was done to prevent degradation and improve the electrochemical performance of Li4Mn2O5 using coatings and alternative electrochemical testing procedures. F, Ni, Zn and Na doping were also investigated as ways to improve the capacity retention. Na doping was found to provide the best capacity retention of 78.9% after 20 cycles. Finally, EOL and QC LMO were upcycled into Li4Mn2O5 and Li2MnO2.25F which performed with a comparable electrochemical performance to DRS made using pristine starting materials.
This work details a method for the separation of mixed cathodes containing LMO and LO. It also demonstrates a method to upcycle lower value cathode materials, such as LMO, into current and next generation cathode materials, such as LMNO and DRS materials
Autonomy, migration and transculturality: From Peele, Shakespeare, and Gay to the Windrush Generation
'Autonomy, Migration and Transculturality: Peele, Shakespeare and Gay to the Windrush Generation' is a tripartite conversation brought together with a collectively defined goal to re-member, re-connect, and reconcile the seemingly disparate triangulation of themes, epochs, and locations. The catalyst for this Literary-Geohistorical Enquiry project was a collision of literary, geographical, and historical migrations.
To explore these migrations, I have researched and explored a series of Literary-Geohistorical Enquiry Questions, such as: What are the key determinants and connective tissue that ignites and informs the conversation between these particular migrations? How do the lives and writing of George Peele, William Shakespeare, and John Gay converse with real-world migrations? How does the writing of George Peele, William Shakespeare, and John Gay converse with each other? Are there traces of these encounters and periods of mobility continuing in our contemporary world?
Consolidating the fragmented understanding of the cross-cultural encounters within and between the literature, histories, and geographies, this interdisciplinary, intertheoretical scholarship seeks to demonstrate their interrelationships
Optimizing woodchip biochar for adsorption of inorganic metal ion contaminants
Affordable, reliable, and low-cost methods for removal of oil-associated heavy metal contaminants (Ni and Pb) from the environment are urgently needed. The use of adsorbent’s produced from organic biomass which is a renewable feedstock has gained attention recently. In this work, seven woodchip biomass samples (Ash, Apple, Alder, Beech, Birch, Cherry and Oak) were characterized in terms of their surface area, pore size, pore volume , elemental composition (Carbon, Nitrogen, Hydrogen, Oxygen), moisture, volatile substances, heat content , and metal ion concentrations (Mg, Mn, P, Ca, Co, Cu, Cr, Fe, Ni, Cd, Pb) and statistically compared using Pairwise non-parametric Kruskal-Wallis one-way ANOVA) to identity a subset based on significantly ( MHA-Bc (0.49 mg/g) HABc> (0.49 mg/g). Nanomaterial functionalization of biochar reduced the number of active sites for sorption but added a new attachment mechanism (complexation) to the existing one (precipitation), thereby enhancing the overall adsorption efficiencies