Research Theses Submission

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    Metaheuristics and machine learning for joint stratification and sample allocation in survey design
    (University College Cork, 2022-01) O'Luing, Mervyn; Prestwich, Steve; Tarim, Armagan; European Regional Development Fund; Science Foundation Ireland
    In this thesis, we propose a number of metaheuristics and machine learning techniques to solve the joint stratification and sample allocation problem. Finding the optimal solution to this problem is hard when the sampling frame is large, and the evaluation algorithm is computationally burdensome. To advance the research in this area, we explore and evaluate different algorithmic methods of modelling and solving this problem. Firstly, we propose a new genetic algorithm approach using "grouping" genetic operators instead of traditional operators. Experiments show a significant improvement in solution quality for similar computational effort. Next, we combine the capability of a simulated annealing algorithm to escape from local minima with delta evaluation to exploit the similarity between consecutive solutions and thereby reduce evaluation time. Comparisons with two recent algorithms show the simulated annealing algorithm attaining comparable solution qualities in less computation time. Then, we consider the combination of the k-means and clustering algorithms with a hill climbing algorithm in stages and report the solution costs, evaluation times and training times. The multi-stage combinations generally compare well with recent algorithms, and provide the survey designer with a greater choice of algorithms to choose from. Finally, we combine the explorative properties of an estimation of distribution algorithm (EDA) to model the probabilities of an atomic stratum belonging to different strata with the exploitative search properties of a simulated annealing algorithm to create a hybrid estimation of distribution algorithm (HEDA). Results of comparisons with the best solution qualities from our earlier experiments show that the HEDA finds better solution qualities, but requires a longer total execution time than alternative approaches we considered.
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    Designing public playgrounds for inclusion: Universal Design for Play (UDP), a tailored perspective
    (University College Cork, 2022-08-31) Moore, Alice; Lynch, Helen; Boyle, Bryan; Irish Research Council
    To extend knowledge on how to enable outdoor play, social participation, and inclusion in public playgrounds, the overall aim of this thesis is to establish an evidence base for using Universal Design (UD) for public playground design. The scope of this doctoral research encompassed a multi-layered approach to understanding this complex concept of UD from a higher conceptual level as well as an applied level. It includes five studies that employed multiple methods to review published and grey literature as well as explore the perspectives of “professional experts” and “user experts”. Study I included a review of evidence for using UD in public playground design. Specifically, a scoping review of peer reviewed literature was undertaken to identify and synthesise what is known from published, peer reviewed studies about inclusive public playgrounds, underpinned by a commitment to understanding the concept of UD as it applies specifically to public playground design. Findings show that although UD is recognised to have the potential to support the design of public playgrounds, the evidence is currently very sparse and identified the gap in knowledge internationally of how UD is understood as a concept. Study II included a review of the conceptual understanding of UD in public playground design. Indeed, this consisted of a scoping review to determine how UD and related non-discriminatory planning and design concepts are represented in the context of published research exploring public playground design for inclusion. Findings revealed that that the terms UD, inclusive design, accessibility, and usability are all being used to describe non-discriminatory planning and design processes arbitrarily and without regard for higher or lower order concepts, which has potentially led to inconsistency and confusion. Altogether, diverse interpretations of UD were evident; for some UD was understood as a basic concept resulting in accessibility, for others, UD was more holistic in terms of designing for inclusion. In Study III, scoping review search methods were developed and applied to synthesise findings from a review of international grey literature guidelines for the design of public playgrounds for inclusion and sought to determine the evidence for using UD and play value in public playground design. Findings highlighted that although UD is recognised to have the potential to support the design of public playgrounds, inconsistent design approaches, principles, and recommendations, were communicated among the included guideline documents. However, the core concept of inclusion underpinned all guideline documents, and a tailored application of UD dominated. Study IV involved survey methods to determine the ways in which UD is understood and implemented, when planning, designing, and/or providing public playgrounds, from the perspectives of a national sample of playground professionals in the Republic of Ireland. The findings show that playground professionals recognise the importance of UD and implement UD in various ways. However, significant barriers to implementing UD included a lack of knowledge and good practice guides for embedding UD. To counteract these barriers, a variety of opportunities, initiatives and training prospects were identified. In Study V, a qualitative descriptive study sought to explore the experiences of using playgrounds, as well as the reasons for non-use, from child and adult perspectives, through the lens of play and play value to inform UD. Findings emphasised that although children and adults value playgrounds as spaces for outdoor play, social participation, and inclusion, playgrounds are not always useable, and do not always meet the needs of families. Participants in this study confirmed that there are variable standards when it comes to playground provision, and some facilities lack essential elements for outdoor play, social participation, and inclusion. Nevertheless, participants offered many creative ideas to improve the usability of playgrounds, and therefore, identified potentially practical ways of implementing UD in playground design for inclusion (Chapter Seven). In conclusion, this doctoral research contributes with an evidence base for using UD for public playground design both at a conceptual and an applied level. It challenges the current UD concept and argues for further conceptual refinement to consolidate the importance and future application of UD for Play (UDP) in the design of public playgrounds that promote outdoor play, social participation, and inclusion. Moving forward the challenge is to promote the universal establishment of inclusive public playgrounds that offer high play value and include all persons in everyday occupations without injustice.
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    Investigating the host-microbe dialogue in aging
    (University College Cork, 2022-12-16) Killian, Christina; Joyce, Susan; Clarke, David J.; Eli Lilly and Company
    This thesis aimed to investigate the role of the gut microbiota and their associated functionality in the context of aging and life stage related diseases. The focus was maintained on key inter-kingdom signalling molecules, host produced but bacterially modified Bile acids (BAs) and on dietary microbially derived Fatty acids (FAs) as key elements to indicate gut microbial potential impactful roles. In the context of Chapter 3, this thesis examined the levels of BAs and FAs, to identify convergence on specific microbially produced, or modified, metabolites in the two neurological disease states representing (1) early life (murine model of Autism Spectrum Disorder (ASD)) and (2) later life (human Parkinson’s Disease (PD)). It further established the potential to redress the balance through microbial intervention, as a cause or consequence in the case of ASD. BAs converged during the healthy aging process, in Chapter 4, to determine the nature of these specific interactions, based on nuclear receptor conservation. The Caenorhabditis elegans nematode model of aging was employed to determine and genetically decipher potential individual BA influences. Chapter 5 built on recognising that gut microbes and the pathobiont Escherichia coli HM605 induced inflammation. This chapter also focused on the mechanisms by which Escherichia coli HM605 could influence the aging process.
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    Regulation of intracellular trafficking of the insulin-like growth factor I receptor
    (University College Cork, 2023) Godsmark, Grant; O'Connor, Rosemary; Science Foundation Ireland; Swiss Forum for International Agricultural Research
    Insulin-like Growth Factor 1 and its receptor (IGF-1R) are required for normal cellular growth, but aberrant expression is linked to the progression and development of many malignancies. Despite IGF-1R being a promising cancer therapeutic target, clinical targeting has not been generally successful. This has also highlighted gaps in our knowledge on IGF-1 signalling and how the IGF-1R and its regulatory regions function. Two tyrosine residues Tyr1250/1251 located within the 1248SFYYS1252 signalling motif of the IGF-1R are required for receptor internalisation, transformation and Golgi localisation. This thesis aimed to further investigate how this region and the C-terminal tail contribute to IGF-1R trafficking, sub-cellular localisation and regulation by using a range of cell lines and IGF-1R receptor mutants. Phosphorylation of Tyr1250/1251 was shown to be required for IGF-1R localisation to the Golgi and that a phosphomimetic EE (Y1250E/Y1251E) IGF-1R mutant is less stable, is more ubiquitinated and undergoes more rapid proteasomal degradation than wild type IGF-1R. Three lysine residues (Lys1256, Lys1294, Lys1324) were identified within the IGF-1R C-terminal tail as putative ubiquitin binding sites, but mutation of these to arginine in mutational studies established that all of these sites have a minor function in receptor ubiquitination. Peptides encompassing the hydrophobic Tyr1250/1251 site in the IGF-1R were recently proposed as a cargo-sorting motif that binds to the protein trafficking ESCPE-1 (SNX5/SNX6) complex, which rescues the IGF-1R from lysosomal degradation. This was tested this using full-length receptors expressed in different cell models and using siRNA-mediated suppression of SNX5/SNX6. However, our data did not replicate the published observations on SNX5/SNX6 knockout causing reduced IGF-1R protein expression. Furthermore, no effect of SNX5/SNX6 suppression on IGF-1R protein levels or location at different sub-cellular compartments including the Golgi was observed. Interestingly, SNX5/SNX6 suppression induced lysosomal accumulation at the leading edge of cells as well as decreased cellular migration. SNX5/SNX6 was observed to interact with the IGF-1R, but the hydrophilic Y1250E/Y1251E mutant exhibited a stronger interaction, than the hydrophobic Y1250F/Y1251F mutant, which suggest that this interaction may be modulated by phosphorylation in the full-length receptor. In summary, the findings confirm the importance of the IGF-1R C-terminal tail, in particular, Tyr1250/1251, in IGF-1R signalling and regulation. These tyrosines facilitate ubiquitin binding, SNX5/SNX6 interaction and Golgi localisation of the IGF-1R which all contribute to the transformed phenotype. Further research on the associated mechanisms should assist in tailoring future cancer therapy treatments to improve clinical efficacy.
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    Statistical modeling strategies for estimation of the arterial input function in dynamic positron emission tomography data analysis
    (University College Cork, 2023-03) Xiu, Zhaoyan; Huang, Jian; Wolsztynski, Eric; Science Foundation Ireland; European Regional Development Fund; National Cancer Institute; National Institute of Aging
    Kinetic modelling of dynamic PET data requires knowledge of tracer concentration in blood plasma, described by the arterial input function (AIF). Arterial blood sampling is the gold standard for AIF measurement, but is invasive and labour intensive. A number of methods have been proposed to accurately estimate the AIF directly from blood sampling and/or imaging data. In this work, we review some of the main methodologies for AIF estimation, and present two alternatives that aim at addressing some of their major limitations. We developed a tracer travel rate projection model as an early AIF modelling attempt based on tracer travel history in the circulatory system. A penalty was considered for model parameter estimation and we used arterially sampled data for evaluation. To improve on this first model, we developed a population-based projection model that exploits historical data to estimate individual AIFs. We represent the history of a tracer atom at a sampling site by its travel time, modeled as a sum of the time for the atom to initially progress from the injection site to the right ventricle of the heart, and the time it spends in circulation before being sampled. The former is modeled as a realization from a gamma distribution, whose parameters are common to all subjects in the population, and estimated from a collection of arterial sampling data for the given tracer. The latter is represented by a subject-specific linear mixture of these population pro- files. This approach can be seen as a projection of individual AIF characteristics onto a basis of population profile components. It also incorporates knowledge of injection duration into the model fit, allowing for varying injection protocols. Analyses of arterial sampling data from 18F-FDG, 15O-H2O and 18F-FLT clinical studies show that the proposed model can outperform reference techniques. The statistically significant gain offered by using population data to train the basis components, as opposed to fitting these from the single individual sampling data, is measured on the FDG cohort. Kinetic analyses demonstrate the reliability and potential benefit of this approach in estimating physiological parameters. These results are further supported by numerical simulations that demonstrate convergence of the proposed technique with decreasing noise levels, and stable levels of performance under varying training population sizes and noise levels.