University of Birmingham Research Archive, E-theses Repository

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    11811 research outputs found

    Primary school staff’s views and experiences of working with children of imprisoned parents/carers: a case study exploration

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    Parent/carer imprisonment (PI) is classed as an adverse childhood experience (ACE) and there are estimated to be over 100,000 children in the United Kingdom (UK) experiencing PI at the time of writing. There is a vast body of international research which has highlighted associations between PI and adverse outcomes/impacts, such as anti-social behaviour (e.g., Ruhland et al., 2020), poor mental health and wellbeing (e.g., Davis & Shlafer, 2017), and negative school related outcomes including school non-attendance or withdrawal, low academic achievement, fighting and truancy (e.g., Bell et al., 2023; McCauley, 2020; Trice & Brewster, 2004). Some research has also found negative outcomes to extend into adulthood (e.g., Huebner & Gustafson, 2007; Murray & Farrington, 2005). Education settings are viewed as having a key role in supporting children of parents/carers in prison (CoPiP) (Roberts & Loucks, 2015; Tuite, 2016) and there is some local authority (LA) and charity guidance on how schools can support this group. To date, limited research has explored the needs of children of CoPiP in school and what support is currently available to them in UK educational settings. This current study explored mainstream primary school staff’s views on how CoPiP present in school, current practice for supporting and responding to these pupils in school, and what further support is perceived to be needed. A case study design was adopted, with the research taking place in one mainstream primary school in the Northwest of England. Individual semi-structured interviews were conducted with five staff members in this setting which were analysed inductively using reflexive thematic analysis (RTA). Findings indicated that some CoPiP are perceived to experience challenges in school, specifically academic difficulties, poor school attendance, and emotional and behavioural challenges. CoPiP were also viewed to seek increased adult connection in school, and it was also cited that challenges or adverse changes are not always apparent. In terms of current school practice, CoPiP were found to be supported through various means in the case school; considering and adapting the curriculum, time with adults who they can connect with, as well as offering individualised, flexible support and extending support to the wider family. Information sharing with and within school was viewed as both a means of current support and where improvement was desired. Finally, staff training was spoken of as a way that support could be strengthened. The implications for professional practice and further research are considered in this paper

    Trauma and Treatment interference in forensic populations

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    This thesis comprises four chapters. The first chapter is a meta-analysis of the prevalence of post traumatic stress disorder (PTSD) in female prison populations. Twenty articles were included, reporting a total of 7266 participants. The average PTSD prevalence was 24%. Sensitivity analyses found lower rates of prevalence when diagnostic interviews were conducted by psychiatrists and clinical psychologists, compared to other professionals. The risk of bias found in some of the studies highlights a need for future research to use more rigorous methodology to minimise risk of bias. Recommendations are made for increasing the diagnosis and treatment of PTSD in prisons to improve outcomes for those living with PTSD. The second chapter is an exploratory analysis of predictors of successful and non-successful outcomes at HMP Grendon. A series of binary logistic regressions were conducted, and a clinical regression decision tree was calculated. The clinical regression tree was able to predict non-successful outcomes with an overall accuracy of 97.6%, but successful outcomes with a 7.9% accuracy. Men who self-report high Antisocial Features, Treatment Rejection and Dominance, and low Social Self-Esteem, have a 98.1% chance of a non-successful outcome. This predictive model holds significant clinical implications, enabling the identification of treatment-interfering factors. This information could be used to adjust treatment accordingly and reduce the number of people that leave Grendon with a non-successful outcome. Further research is required to understand common psychometric profiles that accurately predict successful outcomes. The third and fourth chapters consist of press releases for the first and second chapters

    Phenotypic profiling of mycobacterial mutant libraries, through chemical-genomic screening

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    The genus Mycobacterium encompasses numerous important human and environmental pathogens including the causative agent of tuberculosis, Mycobacterium tuberculosis, which is responsible for around 1.5 million deaths each year. Although curable, the treatment for M. tuberculosis is extensive and antibiotic resistance is an ongoing concern. Therefore, there is a demand for the development of new anti-mycobacterial drugs. Functional characterisation of mycobacterial genomes could lead to the discovery of new drug targets and help to characterise drug resistance pathways. However, mycobacterial genomes are poorly characterised with ~25% of the M. tuberculosis genome remaining functionally unannotated. Therefore, new methods are required for the characterisation of the outstanding genome. Ordered mutant libraries are extremely valuable resources that not only provide a catalogue of mutants for further study but can also be combined with functional genomics to help characterise bacterial genomes. As Mycobacterium abscessus genetic resources are limited, we constructed an ordered M. abscessus mutant library. The library was constructed via random transposon mutagenesis using the phage delivery vector, ΦMycoMarT7, in which 18,432 mutants were manually ordered into 96-well plates. Although we were unable to finish the deconvolution of the library, once complete, this library will represent the largest collection of M. abscessus mutants in existence. To demonstrate the utility of ordered libraries for functionally characterising bacterial genomes, we optimised a method for the chemical-genomic screening of mycobacteria using a M. bovis BCG mutant library. We first condensed the M. bovis BCG mutant library so that it was compatible with high-throughput screening. To increase experimental throughput and reduce human error, we implemented robotics to develop the chemical genomics method. In this method, M. bovis BCG liquid source plates were replicated in a 384-colony format onto solid agar replica plates containing sub-inhibitory concentrations of different perturbations. Colony morphology and mutant fitness was then assessed via IRIS and ChemGAPP. To validate the method, we conducted a pilot screen using 2 library plates and 22 conditions and discovered 76 mutants had significant fitness changes in response to at least one condition, many of which had insertions in genes that had not been previously characterised. Through clustering analysis, we also identified various uncharacterised genes that may fulfil roles in important biological pathways. Lastly, we developed a pipeline for validating the screening hits in which markerless mycobacterial gene deletion mutants were generated via ORBIT and phenotypically characterised via microscopy, growth kinetics and chemical screening. This research contributed towards the discovery of two cell-wall associated enzymes, the D,Dcarboxypeptidase, LpqF, and the α-1,6 mannanase, MSMEG_0740 (Rv0365c). Therefore, taken together, this work outlines a method for characterising mycobacterial genomes through the generation of ordered mutant libraries, functional genomics and reverse-genetic phenotyping. Using this pipeline, we successfully generated an ordered M. abscessus mutant library which will represent a useful resource for future study, we conducted a pilot functional genomic screening to phenotypically profile mutants of numerous previously uncharacterised genes and through reverse-genetics, we also discovered two new enzymes involved in the synthesis and recycling of the mycobacterial cell wall

    Long-term outcomes of Tetralogy of Fallot following complete repair

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    Background: Tetralogy of Fallot (ToF) is the most common cyanotic heart defect, requiring not only early surgery in infancy, but usually one or more cardiac catheter interventions or open-heart operations into adulthood. Although ToF is ‘completely repaired’ at the initial surgery by closing the ventricular septal defect (VSD) and relieving the obstruction to pulmonary blood flow, it invariably leaves severe pulmonary valve regurgitation with volume loading of the right ventricle (RV). Over time, the RV dilates and will eventually fail without further intervention to implant a pulmonary valve prosthesis. We analysed early and late outcomes of ToF in one of the largest single-centre cohorts of both paediatric and adult congenital cardiac surgery in the UK, with a consistent approach to operative management over more than 30 years. Methods: All patients who underwent complete repair of ToF over a 34-year period (1988-2022) in a single centre were included. Comparisons between morphological groups were undertaken using the Kruskal-Wallis tests for continuous variables, or Pearson's chi-squared test for categorical variables. Kaplan-Meier estimates were generated as all-cause mortality curves for the time-to- event analysis, and comparison between groups using the log-rank test. Event rates for reinterventions were estimated using cumulative incidence function with death as the competing risk. Results: 821 patients were included in the final analysis with a median follow-up of 15.1 years over a study period of 34.3 years. 24% underwent a pre-repair intervention: either a systemic-to-pulmonary shunt or a right ventricular outflow tract stent. Median age at repair was 0.98 years with 95% of patients undergoing a trans-atrial approach to the VSD closure. 74.4% required a transannular patch. Long-term survival was 92.5% at 30 years. Median interval from complete repair to pulmonary valve replacement (PVR) was 18.2 years. Incidence of PVR at 25 years was 39.1% with 50% of patients needing a PVR at 27 years. Following PVR, there was a decrease in the indexed right ventricular dimensions including end-diastolic volume (from 119ml/m2 to 103ml/m2) and end- systolic volume (84ml/m2 to 52ml/m2) with an associated increase in the right ventricular ejection fraction. Conclusions: We demonstrate excellent long-term results for Tetralogy of Fallot over a 34-year study period with evidence of reverse remodelling following pulmonary valve replacement. This study provides a sound evidence-base to counsel parents about long-term outlook for children treated with Tetralogy of Fallot

    A physics-based approach to modelling the surface integrity of machined nickel-based superalloys

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    This thesis presents a novel method for predicting flow stress behaviour of nickel-based superalloys through the use of a newly developed microstructure informed constitutive model. Implementing the constitutive model within a finite element scheme has allowed simulations of the deformation and stress evolution, as well as microstructural changes induced by the machining process. Predictions of microstructural changes include grain refinement, γ′ distortion, and dissolution of γ′ precipitates. The constitutive model has predicted the experimentally observed ‘white layer’, showing grain refinement and γ′ distortion. These predictions will allow optimisation of the machining process to reduce the white layer, and aid in development of new alloys. The newly developed constitutive framework predicts flow stress behaviour of precipitate strengthened alloys, taking into account the effects of a multi-modal precipitate distribution. The model includes descriptions of deformation micro-mechanisms by dislocation climb/glide and dislocations shearing precipitates, as well as a mean-field approach to modelling precipitation kinetics. The model was implemented within finite element simulations to predict flow stress behaviour during compression tests, and microstructural changes during machining, of nickel-based superalloy, RR1000. Validation of the constitutive model was performed by comparison of model predictions to experimental data obtained from compression tests of RR1000. The model showed good agreement on yield stress data, and described the flow stress characteristics of the material. The constitutive model was implemented within finite element simulations of the machining process, predicting the formation of an elastic shear band within the workpiece which acted as a nucleation site for microstructural changes. The predictions described how the chip formation process was a result of tensile stresses within the shear band and showed that accumulation of damage and opening of voids in the centre of the band was where the chip first started to form. The model described how reaction forces were a consequence of the chip formation process, and how the force can be related to γ′ shearing to give a real-time indication of the machinability of a material. Additional simulations were performed to determine the impact of different cutting speeds, workpiece temperatures, and various γ′ dispersions, on machinability. By varying the initial secondary γ′ precipitate dispersion, the model demonstrated how a decrease in the interparticle spacing provided more dislocation pinning obstacles, which provided greater resistance to deformation

    Reward-based improvements of motor performance in health and disease

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    Reward has been found to boost motor performance and improve learning in both healthy individuals and in clinical populations. The aim of this thesis was to gain a better understanding of how reward affects different specific aspects of motor performance and learning across various age and health status groups. This work provides an important step towards optimising the use of reward within clinical populations such as stroke patients. The introductory chapter (Chapter 1) provides a comprehensive review of relevant literature, setting the stage for the investigations that follow. As motor performance and reward responsiveness tend to decline with age, Chapter 2 investigated the age-related differences in reward-based improvement in motor performance. We observed that both young and older adults showed improved performance with rewards, but the young group exhibited significantly higher reward-based enhancement in motor performance. In chapter 3, we extended these results by examining how reward impacts motor performance in stroke patients. In this study, we also investigated the impact of rehabilitation on reward sensitivity. Our findings suggest that stroke patients' motor performance significantly improved with the presence of reward. We also found that patients' performance improved after rehabilitation, but there were no changes in reward sensitivity. Chapter 4 investigated the role of the primary motor cortex within the reward-based enhancement of motor performance using repetitive transcranial magnetic stimulation. No effects on performance were observed. In Chapter 5 of this thesis, we explored how reward affects sequential movements and how manipulating task difficulty can impact reward-based improvement in sequential movement fusion. Our findings suggest that sequential movement fusion is more effective when the task is easy, and this effect is further enhanced by the presence of a reward. The thesis concludes with Chapter 6, which synthesizes the findings, discusses their implications, and proposes directions for future research. This study not only advances our understanding of reward-based motor learning but also provides a foundation for optimizing reward utilization in clinical settings, offering hope for improved rehabilitation strategies

    Visual 6D object pose estimation and tracking

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    Visual 6D object pose estimation and tracking is crucial for enabling machines to understand and interact with the three-dimensional world. Despite significant advancements, challenges persist in this field. Existing methods often struggle in complex real-world scenarios, particularly with symmetric and textureless objects under occlusion. Category-level methods also face limitations in generalizability, especially with complex-shaped objects and noisy environments. Additionally, there is a significant gap in effective methods for category-level object pose refinement, which is crucial for achieving high-precision pose information with previously unseen objects. To address these challenges, this thesis proposes three approaches. First, an instance-level object pose tracking method is introduced, leveraging temporal information with augmented autoencoder-based reconstruction to enhance robustness to symmetric and textureless objects under occlusion. Second, a hybrid scope feature extraction layer (HS-layer) is presented for category-level object pose estimation. The HS layer encodes translation and scale information, perceives geometric structural information for handling complex-shaped objects with robustness to outliers. Lastly, a method that combines latent geometric feature extraction and learnable affine transformation is proposed to address shape discrepancy issues in category-level object pose refinement, improving pose refinement accuracy and generalizability. Extensive experiments validate the effectiveness of these approaches in advancing practical applications of visual 6D object pose estimation and tracking. Additionally, all the proposed methods exhibit real-time performance, crucial for real-life applications

    From graph minor theory to 3-dimensions

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    This thesis comprises of three projects from topological combinatorics and structural graph theory. Firstly, we extend Heawood's theorem on the colourability of plane triangulations to triangulations of 3-space by proving that a triangulation of 3-space can be edge coloured with three colours if and only if all edges have even degree. Next, we propose an open question that seeks to generalise the Four Colour Theorem from two to three dimensions and show that 12 instead of four colours are both sufficient and necessary to colour every 2-complex that embeds in a prescribed 3-manifold. However, our example of a 2-complex that requires 12 colours is not simplicial. We give bounds on this colouring number for simplicial 2-complexes. Lastly, we look at graphs that are not 1-tough and consider the set of minimal seperators of these graphs that "witness" the non-toughness of the graph

    Towards exploring protein clusters: determining stoichiometry and recruitment kinetics via single molecule microscopy

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    Cells are dynamic systems, in which proteins regularly form complexes of changing stoichiometry. However, molecular counting techniques are mainly performed on fixed cells, thus losing the temporal aspects of complex formation, which might have revealed additional information of underlying biological processes. This PhD thesis presents developments to the quantitative microscopy technique Counting by Photon Statistics (CoPS), contributing towards towards making the technique a live cell compatible method. The work involved constructing a microscopy setup with the ability to acquire antibunching data, as well as to support widefield modalities. The microscope characteristics were defined and CoPS measurements on it were validated. A molecular standard with consistent DNA-hybridisation kinetics, the rates of which were defined, was used to test new dynamic versions of CoPS better suited for continuous data. However, photodestruction of the model system was observed with Cy5 labelling, which decreased when labelled with Atto 643. Experiments on cells were conducted to explore the challenges of in cellulo CoPS. The optimal imaging conditions were explored and CoPS experiments were conducted on a cellular molecular standard. The recruitment of the adaptor protein SLP-76 protein was also inspected as a dynamic system of protein recruitment, and the stoichiometry of its clusters was identified. A new technique for determination of the degree of labelling (DOL) was developed to facilitate the accuracy of these measurements. The limiting factor of live cell CoPS was determined to be the photophysics and photostability of the fluorophores. For the technique to work a further large study of different fluorophores and live cell buffers was identified as a direction of future experiments

    Rethinking theory of mind measurement in neurotypical adults: response generation and selection

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    The research on mindreading in adults has proliferated over the past two decades, but not all measures are equally suitable for assessing individual differences in mindreading performance among neurotypical adults. This thesis presents a systematic review of the measures used to evaluate mindreading in neurotypical adults, identifying measurement challenges and a limited evidence base for assessing the psychometric properties of even popular measures. Additionally, focusing on tasks that present social stimuli without a known ground truth of the mental states of portrayed characters, this thesis proposes alignment, or social agreement, as a practical alternative criterion for mindreading success instead of “accuracy”. A series of eight empirical studies were conducted to examine the presence of multiple legitimate mental state interpretations, task-related factors influencing these interpretations, and the role of context in the generation and selection of mental state interpretations. The results challenged the notion of a single best mental state interpretation of ambiguous social stimuli, revealing multiple popular interpretations among participants that varied between groups, and that the format of the task and contextual information about the depicted social interactions influenced mental state interpretations. The findings also provided support for studying the generation and selection of mental state interpretations as distinct processes, with context strongly influencing the selection of the best interpretation while more weakly constraining the generation of plausible interpretations. Possible indices of individual differences in adult mindreading were explored, showing that the tendency to generate multiple interpretations was a more promising direction than alignment and flexibility to adjust interpretations with reference to changes in context. The concluding chapter summarises the findings, discusses the implications and limitations of the current studies, and suggests future research directions for measuring mindreading in neurotypical adults and unravelling the cognitive basis of mindreading

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