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Movement and cognition in Autism and Parkinson’s Disease: similarities, points of distinction, and underlying biological mechanisms
Get PDFAn increased prevalence of Parkinson’s Disease (PD) diagnosis is apparent in the autistic (ASD) population. However, genetic studies have failed to provide evidence for a strong link between the two conditions, meaning it may not be the case that autistic individuals are genetically more likely to develop PD. Anecdotally, movement differences in ASD have been likened to those exhibited by individuals with PD. Given that PD diagnosis is primarily movement-based, similarities in ASD and PD movement may explain the increased PD diagnosis prevalence in the autistic population: if it is indeed the case that autistic movement appears parkinsonian, this may facilitate autistic individuals meeting diagnostic criteria for PD. This could have serious implications for the specificity of the PD diagnostic process. With a lack of direct comparison studies assessing behavioural and cognitive profiles in ASD and PD, it is unclear whether quantifiable similarities exist between the two conditions. Extant evidence for a potential overlap between the two conditions relies on the comparison of findings from separate research studies, and thus is limited due to variation in participant demographics and tasks used.
In this thesis I conducted the first direct comparison of behavioural and cognitive profiles in ASD and PD, in addition to members of the general population. Chapter 2 demonstrated many similarities in the kinematic features of animations (free movement) produced by the ASD and PD groups, but only the similarity in jerk between ASD and PD was distinct from performance in the general population. All three groups were additionally comparable with respect to movement-based theory of mind ability. Chapter 3 conducted a more sensitive investigation of autistic and parkinsonian movement using a restricted movement task devoid of theory of mind demands. Here, kinematic features were uncovered that differed between the three groups (e.g., speed modulation, sub-movements and reaction time). This Chapter also determined the utility of movement assessments for classifying group membership, demonstrating higher levels of classification accuracy when trait questionnaires were combined with kinematic features in a range of classification models. This highlights that clinical diagnostic processes may be improved through the incorporation of kinematic assessments.
Alongside providing insight into the behavioural and cognitive similarities between ASD and PD, the thesis presented novel findings with respect to ASD and PD separately. For example, Chapters 2 and 3 conducted the first kinematic assessments of older autistic adults, revealing that some, but not all, components of younger autistic movement remain distinct from non-autistic movement in older age. In addition, the first assessment of individuals with PD on the tasks presented in Chapters 2 and 3 revealed novel kinematic features that differed in this population (e.g., speed modulation), and patterns of movement speed differences between the two Chapters were aligned with the motor motivation hypothesis of PD.
Finally, Chapter 4 investigated biological mechanisms underlying movement differences between the three groups, setting out evidence from two pharmacological intervention studies. Specifically, movement differences resulting from PD dopaminergic medication and the dopamine antagonist haloperidol were explored. These studies implicated dopamine in a range of ASD- and PD-relevant kinematic features, strengthening the proposal that movement differences in ASD and PD are the product of dopaminergic mechanisms. Results across the three Chapters are consistent with hyper-dopaminergic functioning in ASD and hypo-dopaminergic functioning in PD. Overall, this thesis provides a greater understanding of the overlap between behavioural and cognitive presentations of ASD and PD, as well as underlying biological mechanisms which may account for this overlap
(De)politicization and the politics of Containment: Reconceptualizing the role of the public inquiry within British Governance
Get PDFThis thesis examines the role public inquiries play within British governance. Public inquiries are called in response to high-profile matters of public concern and are tasked with investigating these independently of Parliament. Ostensibly, inquiries deliver accountability, policy learning and an accurate account of what went wrong. From a more critical perspective, however, public inquiries are a tool of the state, whose usage primarily benefits state managers in their attempts to manage crises, avoid blame, and secure their survival and legitimacy. Adopting a statecraft perspective, which focusses on the role inquiries play within the politics of governing, and drawing on archival material, parliamentary debates, inquiry reports and secondary literature related to 14 inquiries, the thesis offers a reassessment of what state managers hope to achieve when they initiate inquiries. It is argued that inquiries are utilized strategically and rhetorically by state managers to relieve pressure immediately post-crises, maintain governmental autonomy in the face of demands for change from below, and avoid blame for failings. In detailing empirically the processes by which state managers utilize inquiries as part of attempts to achieve these aims, the thesis ultimately arrives at a reconceptualization of the public inquiry’s position within British governance. The public inquiry is situated within ongoing processes working to depoliticize crises and contain popular discontent by funnelling it into formalized political arenas where it can be managed and moderated. This reconceptualization of inquiry functionality reveals the elitist, closed-off nature of British democracy and Britain’s formal political institutions. This also indicates the disruptive effects popular discontent can have on crisis management, and that it is a key danger that state managers must seek to quell
Spatio-temporal mechanisms of microplastic transport in rivers: from mountains to sewage outflow
Get PDFThe spatio-temporal distributions of microplastic (MP) in three river systems affected differently by urbanization were investigated, with the aim of identifying key hydrological and source control effects on MP concentrations and MP loadings. The potential effects of MP on ecosystem health were assessed through a systematic literature review, which enabled recommendations for standardization of field and laboratory studies to be made, including using environmentally representative MP shapes and compositions and suggestion for harmonised toxicity endpoints across taxa. A new modified and faster MP identification method via fluorescent tagging with Nile Red was designed to facilitate fast and reliable MP identification and quantification in rivers and catchments that are affected by anthropogenic activities. This new method was applied to investigate how source and hydrological controls influence downstream transport of MP in remote mountainous catchments, downstream of sewage treatment works and to compare point and diffuse MP source activation across contrasting urban catchments. This research evidenced that human influences including water management can have substantial implications for MP load estimations and should be taken into consideration for quantification of catchment residence times of microplastics and river network contributions to the oceans. The results also highlight the need for MP sampling campaigns to give further consideration to how best to achieve more accurate MP sampling, recommendations for which include sampling of water diversions, and conducting pre-monitoring campaigns capturing flow regimens and possible MP fluctuations occurring during the day, especially at locations with varying flow regimen (such as downstream from sewage treatment works) to gain understanding of the minimum sample requirements to produce representative samples for that particular system. Furthermore, this thesis demonstrates that hydrological catchment size may not be descriptive of the MP sources, as the effect of the catchment can be dominated by the presence of a single point source, such as a sewage treatment works, suggesting that water management can play a much more substantial role than typical hydrometeorological drivers within a catchment. For diffuse urban sources, the thesis demonstrates the importance of hydrometeorological events (e.g., rain events) as controls for MP source activation as well as their transport and connectivity to the river network, and the need for sampling across such events to increase understanding the impact of source activation on overall MP loadings
An investigation into vaccine-mediated immune responses against invasive Salmonella Typhimurium infection
Get PDFSalmonella enterica serovar Typhimurium is one of the main causative agents of invasive non-typhoidal Salmonella (iNTS) disease. Resistance to antimicrobial agents is a rising concern, complicating treatment, and prognosis. The need for effective preventative strategies against iNTS is crucial for controlling spread of infection and preventing severe disease. Outer membrane vesicles (OMVs) are naturally shed outer membrane blebs that mimic the bacterial surface and are being explored as a cost-effective vaccine against many infections. Understanding the immunological mechanisms that constitute successful vaccine responses is key for vaccine design. In this thesis, I explored specific innate immune components that are crucial for generating productive immune responses to vaccination with OMVs, resulting in improved ability to control iNTS infections in mice. I showed that complement component 3 (C3) was essential for protection in OMV-vaccinated and challenged mice. Further, I discovered a novel antigen persistence phenotype in OMV-vaccinated and challenged mice. Further investigation of this phenotype revealed that it is specific to OMVs with intact LPSO-Ag chains, and not induced by immunisation with subunit vaccines such as sFliC, or Salmonella Typhi-derived Vi polysaccharide or conjugated vaccines. This phenotype was not influenced by an absence of lymphoid cells, and depletion of macrophages altered the distribution of persistent antigen, however this phenotype was not associated with protection. The results presented in this thesis identify key immune components required for successful protection against iNTS infections in mice, but also potentially pathogenic phenotypes resulting from OMV-vaccination, which bare importance on vaccine design
Investigating the potential senomorphic properties of SCFA butyrate on aged T cells.
Get PDFAgeing is accompanied by remodelling of the T cell pool and a hallmark of immune ageing is the expansion of senescent T cells in aged hosts. Senescent T cells express markers of DNA damage and cell cycle arrest markers, elevated production of pro-inflammatory cytokines as a result of the senescence-associated secretory phenotype (SASP), and accumulation of dysfunctional mitochondria. Importantly, animal studies have brought to light the causal role of senescent T cell accumulation in driving ageing of non-lymphoid organs; highlighting the need to combat the build-up of senescent T cells with advancing age.
Advancing age is also characterised by changes in gut microbiome composition, one consequence of which is a reduction in short-chain fatty acid (SCFA) levels, the products of bacterial fermentation in the gut. Interestingly, our group have reported a negative correlation between stool butyrate levels and senescent CD4 and CD8 T cells in older adults. To elucidate this connection further, in this thesis, we have examined the effect of butyrate on T cell senescent features in healthy young ( 35 years) and healthy old ( 65 years) adults using an in vitro model of proliferation-induced senescence.
Evaluation of the potential anti-senescent effect of butyrate revealed significant reductions in the cell cycle arrest maker p53 and DNA damage marker -H2AX in aged T cells following 3 day culture with 1mM butyrate. We observed potential senomorphic properties of butyrate mediated via attenuation of SASP post butyrate treatment in aged T cells, alongside reductions in the expression of a key SASP regulator, the transcription factor nuclear factor kappa B (NF-B) at both the gene and protein level. Additionally, our findings demonstrated the potential ability of butyrate to decrease mitochondrial mass and ROS production in the T cells of older adults, however this requires further investigation. Consequently, we present butyrate supplementation as a future senomorphic postbiotic treatment to delay the onset of the senescent phenotype and help reduce the healthspan-lifespan gap by combating immunesenescence
Ordered catalyst electrode research and application for PEM fuel cells
No full textOwing to their distinctive surface properties and stability, one-dimensional (1D) nanostructures are considered to be one of the promising avenues for the development of the next generation of proton exchange membrane fuel cells (PEMFCs). However, in comparison with conventional spherical Pt/C nanoparticle electrocatalysts, 1D nanostructures exhibit markedly different behaviour during fuel cell operation. This is attributable to their anisotropic morphology and unique surface structure. The paucity of related fundamental knowledge and detailed mechanisms presents a significant challenge in fabricating high-performance electrodes based on these structures. This PhD research focuses on the development of a novel three-dimensional (3D) ordered catalyst electrode design, predicated upon Pt nanowire arrays (Pt NWAs). It aims to establish a comprehensive understanding of the structure-power performance relationship to inform the development of PEMFCs suitable for high current density operation.
The catalyst electrode featuring a 3D-ordered catalyst layer is achieved through the introduction of a surface modification technique applied to gas diffusion layers (GDLs), thereby facilitating the fabrication of gas diffusion electrodes (GDEs). This is realised by sputtering gold nanoparticles onto the GDL surface to function as crystal seeds, which control the in-situ growth process, thereby forming uniformly distributed single crystal Pt NWAs. Utilising an equivalent thickness of 0.6 nm of Au nano seeds, the AuPt NWA GDE attains a power density of 1.45 W·cm-2, which is 32% higher than that of the GDE fabricated from commercial Pt/C catalyst. The durability of the Pt NWA GDE improves significantly, evidencing only a 43.0% decline after undergoing an accelerated stress test consisting of 42,000 potential cycles; this is in contrast to the 92.9% decline observed in the Pt/C GDE after 20,000 cycles. Subsequently, an orthogonal experiment is conducted to systematically elucidate the operational behaviours of this innovative Au-Pt NWA 3D-ordered electrode design, compared to Pt/C electrodes. The variables examined include temperature, back pressure, relative humidity, and cathode stoichiometry. The analysis reveals that the AuPt NWA GDE exhibits greater sensitivity to operational conditions and identifies back pressure as the most influential factor for performance enhancement.
Lastly, for the first time, a quantification study is carried out on the oxygen transport resistance associated with the 3D-ordered electrodes. This study aims to delineate the distinct contributions from bulk/molecular diffusion, Knudsen diffusion, and oxygen penetration through the ionomer layer on the catalyst surfac
Long-term adverse health outcomes among survivors of childhood, teenage and young adult cancer
No full textBackground: Childhood, teenage and young adult (TYA) cancer survivors are at increased risk of many long-term health complications. This thesis aims to address specific gaps in the existing research regarding the risk of subsequent primary neoplasms (SPNs) and antidepressant and antipsychotic prescriptions dispensed in primary care.
Methods: The PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies (PCSF) includes 69,460 survivors of cancer diagnosed before age 20, across 12 European countries. This data was used to calculate standardized incidence ratios (SIRs) and cumulative incidence of subsequent glioma and meningioma. A nested case-control study, comprising 143 CRC cases and 143 controls, was then used to calculate odds ratios (ORs) for subsequent colorectal cancer (CRC), and cumulative absolute risks (CARs) by attained age and abdominal radiotherapy treatment. The British Childhood Cancer Survivor Study (BCCSS) includes 34,488 British survivors of cancer diagnosed before age 15. The Teenage and Young Adult Cancer Survivor Study (TYACSS) includes 200,945 British survivors of cancer diagnosed between age 15 and 39. Both of these datasets were linked to NHS primary care prescription records for the years 2015-2021, and the data was then used to estimate SIRs and absolute excess risks (AERs).
Results: Within the PCSF cohort, central nervous system tumour and leukaemia survivors were at the highest risk of developing subsequent gliomas and meningiomas, especially following cranial irradiation, and cancer survivors treated with abdominopelvic region radiotherapy were at the most increased risk of a subsequent colorectal cancer. Within the BCCSS and TYACSS cohorts, survivors were at significantly increased risk of being prescribed both antidepressants and antipsychotics, particularly survivors of childhood bone cancer and survivors of TYA cervical and other genitourinary tract cancers.
Conclusions: Survivors of cancer diagnosed before age 40 are at increased risk of a variety of long-term adverse health outcomes. This thesis provides new evidence which should be used by both clinicians and survivors, and in the development and revision of clinical follow-up guidelines
Black-hole dynamics and their environments
Get PDFBlack holes are objects that induce extreme astrophysical phenomena. Several avenues exist to explore how black holes form and how they evolve. In this thesis, I explore the multi-faceted spin dynamics of binary black holes (Part I) and then turn to active galactic nuclei, focussing on theoretical models for the discs around supermassive black holes (Part II). Part I presents a new taxonomy for spin pre- cession of binary black holes, and introduces a new scheme for uncovering different spin precession parameters in gravitational-wave events. Five spin precession parameters are introduced in Ch. 3; one of these is the nutational amplitude which is indicative of two misaligned spins in the black hole binary. A system where the nutational amplitude is maximised is then shown to be recoverable by future gravitational wave detectors in Ch. 4, meaning that spin-spin effects will soon be constrainable. In Part II, I give an outline of active galactic nuclei theory and observations. Chapter 6 investigates two active galactic nuclei disc models by Sirko and Goodman (2003) [1] and Thompson et al. (2005) [2]. Migration formulae are applied to these disc models, recovering the presence of migration traps where black hole capture is likely. The thesis is tied together by the want to understand gravitational wave sources better, which I introduce in Ch. 1
Novel automotive thermal management technologies based on composite phase change materials and nanofluids
No full textIn the context of promoting energy conservation and addressing energy crises globally, the automotive industry, especially the electric vehicle sector, faces significant technical challenges. High energy consumption and insufficient reliability are key factors hindering the development of automobiles, particularly electric vehicles. These issues are primarily concentrated in several subsystems of vehicles such as battery packs, air conditioning, and liquid cooling systems. Batteries are prone to overheating or reduced activity under extreme temperature conditions, air conditioning systems consume a lot of energy, and cooling systems lack efficiency, all of which severely impact vehicle performance and safety. To address these issues, the focus has been on enhancing the actual efficiency of battery thermal management systems (BTMS), improving the energy efficiency of electric vehicle air conditioning systems, and optimizing the performance of automotive cooling systems. The core technologies focused on include the use of Composite Phase Change Materials (CPCMs) to optimize BTMS, the development of Thermal Energy Storage (TES) devices based on CPCMs to enhance air conditioning systems' energy efficiency, and the application of nanofluid automotive coolants to improve the cooling efficiency of automotive cooling systems.
This study employs a combination of experimental and simulation methods. Initially, methods for preparing composite phase change materials and nanofluids were explored, and their material properties were analyzed. Subsequently, the thermal management performance of a flat lithium iron phosphate battery based on phase change cooling was designed and tested. Additionally, a TES device based on CPCM that could provide heating functionality for electric vehicle air conditioning was designed, tested, and its feasibility and actual energy-saving effects were assessed. Finally, the application effects of nanofluids in automotive cooling systems were verified through system-level testing.
The study achieved significant research outcomes:
• The developed CPCM consists of 70wt% capric acid/paraffin (phase change material) and 30wt% OBC (skeletal material), enhanced with 3wt% graphite to improve its thermal conductivity. This material boasts high phase change enthalpy and stable temperature cycling performance, along with excellent shear and compression resistance.
• Tests on BTMS using CPCM containing 3wt% graphite showed that the maximum temperature rise of the battery decreased from 18.3°C to 6.4°C, with an average increase in cooling efficiency of 161.8%. The battery's natural cooling rate more than tripled, extending the time the battery remains at an optimal working temperature, effectively mitigating localized overheating and uneven heat distribution, thus enhancing the battery's safety and operational efficiency.
• In tests on the electric vehicle air conditioning system, a device filled with 4.7 kg of paraffin-OBC-graphite CPCM raised the cabin temperature from 7°C to 14°C in two hours under no sunlight and static conditions, with an average heating output of 193W, saving 0.643 kWh of battery power and extending the driving distance by 4.95 kilometers. Under various outdoor temperatures and weather conditions, the thermal storage device provided over 80W and 160W of effective heating power in two hours, under unlit and lit conditions respectively, effectively reducing the frequency of use and energy consumption of the onboard air conditioning system and enhancing the electric vehicle's driving range.
• Thermal transfer performance tests of nanofluid automotive coolant showed that under the same test conditions, a 1 wt% rGO nanofluid achieved a thermal transfer performance of 4535.3 W, an increase of 1080.3 W over the base fluid, with a thermal transfer coefficient increase of 75.54%-88.55%. Combining the thermal conductivity, viscosity, and suspension stability studies of rGO-DI water nanofluids, the nanofluid demonstrated enhanced heat transfer capabilities and stable suspension properties, contributing to improved engine efficiency and reduced energy consumption.
The innovations of this study are in three technical breakthroughs: firstly, the optimized formulation of CPCMs which are low-cost, easy to manufacture, and also accommodate the characteristics of flexible materials, providing sufficient mechanical protection to the battery and enhancing safety and stability through improved heat dissipation and insulation; secondly, the development of TES devices effectively integrates the energy management of air conditioning systems, utilizing industrial waste heat effectively, reducing energy consumption, and its independent compact system design increases usability; finally, the application of nanofluid technology significantly enhances the performance of cooling systems without physically increasing the heat dissipation area, thereby significantly improving the vehicle's economy and environmental friendliness
The assessment of capacity to support and protect in non-offending guardians in cases of child sexual abuse
Get PDFThe experience of child sexual abuse can have devastating consequences for the child. Research has shown that non-offending guardian support can mitigate the negative impact abuse can have on the child. In practice, it is important for the non-offending guardian to provide support to their child following abuse, but also protection to prevent abuse from happening (again) in the future. In cases like these, expert witnesses may be asked to conduct an assessment to ascertain the non-offending guardian’s ability to provide support and protection to their child. This thesis first explores the current state of literature concerning variables associated with a non-offending guardian’s ability to support and/or protect. This is done using a systematic literature review methodology. Findings reported outline a large list of factors related to either or both the ability to support and protect. Secondly, the thesis explores current practices of expert witness assessments of non-offending guardians’ ability to support and protect their child/ren in cases of child sexual abuse. This chapter also aims to explore to what extent expert witnesses assess some of the factors listed in the preceding chapter. This is done using a qualitative methodology and the data are analysed using template analysis. The findings explore five main themes identified and compare the factors discussed in the literature with current practice. Lastly, one of the psychometric measures used by expert witnesses to aid their decision-making when assessing a non-offending guardian, as reported in the previous chapter, is critically appraised. The Child Abuse Potential Inventory is reviewed and its psychometric properties are discussed. Limitations, implications for practice, and recommendations for future research are discussed in the final chapter of the thesis
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