Statistical methodology for the analysis of road safety data

PhD ThesisPTV Grou

Deciphering liver fibrosis with next generation omics

Ph. D. Thesis.Fibrotic diseases underpin around 45% of all chronic diseases and deaths in the western world. In particular, chronic liver diseases represent a major threat to the public health affecting around 1.5 billion people in the world and accounting for 2 million deaths annually. Hepatic fibrosis is a progressive pathology characterized by a dysregulation of the woundhealing response, resulting in extracellular matrix (ECM) accumulation. Hepatic Stellate cells (HCSs) are the major contributor to ECM deposition in liver diseases. Thus, HSCs are crucial for liver fibrosis progression. Understanding molecular mechanisms of HSC activation is therefore of major interest in study of liver fibrosis. To this end, miRNA sequencing during HCSs activation time-course was employed, which showed significant differences in miRNA expression which may be important for fibrosis progression. 2D cultures are widely used in the study of liver disease. However, they do present limitations, which can be overcome by the use of Bioreactor-cultured Precision cut liver slices (PCLSs) technology developed in our lab. Using this technology, human PCLSs were created and RNA sequencing, proteome and secretome analysis performed. In this thesis, I showed that fibrotic PCLSs present differential gene/protein expression patterns that could be associated with the fibrotic outcome. Previous studies in our lab reported an epigenetic mechanism that generated heritable adaptation in wound healing response in male rats. The adapted rats showed significant fibrogenesis/fibrosis reduction. I was interested in studying the mechanism behind the adaptation. Using omics techniques, I analysed gene expression pattern in adapted livers and differences in DNA methylome and proteome in sperm, as potential mechanism for adaptation transmission. Moreover, I studied the potential of adaptive inheritance transmission via female lineage. This study provides evidence of i) the importance of miRNA during HSCs activation, ii) differential gene/protein expression patterns associated with the fibrotic outcome in human liver, iii) differential gene expression in adapted livers and epigenetic modifications in sperm as a putative mechanism of the adaptive response transmission. This adaptive response was absent in female offspring, suggesting only males can transmit the adaptation.Dr Lorna Jones Legacy gif

Teachers’ and students’ experiences of positive relationships in secondary education

D. App. Ed. Psy. ThesisThis thesis explores experiences of positive Teacher-Student Relationships (TSRs) in secondary education from both teachers’ and adolescents’ perspectives. It is comprised of four chapters: a Systematic Literature Review (SLR), methodological and ethical considerations, an empirical research project and a reflective synthesis. The Systematic Literature Review (Chapter 1) explores teachers’ and students’ experiences of TSRs in secondary education settings. Meta-ethnography was used to synthesise five research papers that were identified as relevant to the review. Findings suggest that teachers and students experience positive relationships as being characterised by kind and friendly interactions, informality and humour and communications that are respectful and equal. Teacher responsivity and sensitivity were identified as important and the concept of going above and beyond for students was discussed. This chapter may support the development of positive TSRs in settings within proximal processes and may also support the development of relational policies in schools. Chapter 2 aims to act as a link between the meta-ethnography and empirical research. Philosophical assumptions are discussed leading to a rationale for the methodology employed. Key ethical considerations are discussed, paying particular attention to the changes to research design and subsequent ethical decisions due to the coronavirus pandemic. The empirical research report (Chapter 3) explores TSRs in upper secondary school in one mainstream secondary setting. Semi-structured interviews were conducted with two teachers and two students from Years 10 and 11 and data was transcribed and analysed using Interpretative Phenomenological Analysis. Perceptions of the culture of relationships in school were found to be important. Findings also suggest that reciprocal interactions filled with human responses, playfulness and care were important. Agency, availability, recognition of responsibility, authenticity and consistency were found to be important elements of positive relationships from teachers towards their students. These findings have implications for teachers, school leaders and for Educational Psychologists. Chapter 4 consists of a reflective synthesis detailing the professional and academic learning acquired through the research journey. In this chapter, what the work means for research and practice is discussed, as well as the next steps for this enquiry. Chapters 1 and 3 have been prepared for publication and are presented in the style of papers typically published by the British Educational Research Journal

Socio-spatial analysis of small-area need and accessibility of Primary Healthcare Services in Nigeria: A sequential mixed methods study

Ph. D. Thesis.Accessibility of primary healthcare (PHC) services is crucial for maintaining the good health of a population. Not only is health(care) associated with quality of life and socioeconomic productivity, systematic variations in healthcare accessibility are matters of social justice. Consequently, the overall goal of this project is to comprehensively analyze and explain smallarea need and accessibility of PHC services in Nigeria through a case study of Kogi State, with a view to making policy-relevant recommendations. To this end, both quantitative and qualitative methods are synthesized in an ‘explanatory sequential mixed methods research design’, which also features innovative data exploitations. This entails a synergy of: Automated Zone Design method, Spatial Microsimulation Modelling, and Generalized TwoStep Floating Catchment Area method for quantitative analysis as well as qualitative framework thematic analysis, to obtain research findings that are more robust than existing studies. In this way, genuine small-area variations in PHC need and accessibility are revealed and explicated, including extreme Medically Underserved Areas (eMUAs). Urban areas are more accessible than rural areas, as expected. Of senatorial districts, Kogi Central has the best healthcare accessibility because of its topography. Furthermore, these variations are mediated by the extant sub-optimal zoning system in Nigeria, which is a product of problematic historical political processes. Not only are eMUAs both very remote and rural, they also lack basic social amenities. Hence, it is not surprising that research participants expressed a myriad of dire disincentives in meeting their PHC needs. These difficulties can be mitigated by improving the quality of road infrastructure and ensuring an optimal socio-spatial configuration of PHC services. Broad mechanisms of social exclusion are also implicated in causing access-related disutility of PHC. It is therefore crucial that holistic interventions to alleviate social exclusion are enacted, since previous efforts at addressing only proximal concerns of PHC accessibility have proven unsuccessful. Keywords: Primary Healthcare Needs, Spatial Accessibility, Mixed Methods Research, Automated Zone Design, Spatial Microsimulation, Small-Area Variations.Newcastle University Overseas Research Scholarship (NUORS), Research Excellence Academy of the Humanities and Social Science Faculty (HaSS RE

Better use of molluscicide pellets for improved management of slugs

Ph. D. Thesis.The grey field slug, Deroceras reticulatum, is one of the most important pests of agriculture, with an estimated 59% and 22% of total planted oil seed rape and wheat respectively affected by slugs in the UK annually. It is estimated that without molluscicides, the cost to the UK’s agricultural industry from loss of crop yield due to slug damage could be in excess of £100 million per year. Metaldehyde is the most commonly used molluscicide in UK agriculture however it presents a large water pollution risk and threat to non-target organisms, in addition, control of slugs by metaldehyde is often inefficient. Understanding how Deroceras reticulatum’s behaviour is affected by the presence of slug pellets with different molluscicide concentrations, and how these pellets affect locomotion, feeding and the health of a slug once a pellet is consumed will help develop more effective slug pellets. The pest-pellet interaction is a key process in successful slug control and can only be effective if slugs accept and consume a pellet when encountered. This research indicated that the concentration of metaldehyde in pellets does not impact on D. reticulatum’s foraging activity, however the presence of a molluscicide may impact on foraging behaviour compared to non-molluscicide pellets. D. reticulatum was more likely to accept and feed on a pellet of lower concentration (1%) compared to higher concentrations (3% and 5%). Paralysis due to the effects of molluscicide is likely to be a key factor in successful slug control. Slugs poisoned with 1% or 3% metaldehyde were more likely to be paralysed after exposure to pellets when compared to higher concentrations, however, were more likely to recover after exposure to 1% pellets. This research has demonstrated that slugs are highly sensitive to metaldehyde. D. reticulatum can detect metaldehyde that has been incorporated using inorganic Controlled Release Technology, with as little as 0.28% metaldehyde content. Controlled release technology involving molluscicides is still in its infancy, however, has potential as a future focus for improved pellet design.Institute for Agri-Food Research and Innovation (IAFRI

Loss Reduction in Axial Flux Machines using Magnetic Shielding

PhD ThesisAbstract– The introduction of compacted insulated iron powder in electrical machines design makes their manufacturing process easy together with high rates of production and the machine parts made from it are stable dimensionally compared to conventional laminated steel. The research work presented in this thesis was carried out with the main aim to improve the overall performance of a three-phase Axial Flux Machine (AFM) using Soft Magnetic Composite (SMC). To realise it, the machine was redesigned in a way to benefit from the unique properties of the material such as low eddy current loss at high frequency, isotropic magnetic properties and simple manufacturing process. Due to the three-dimensional (3D) nature of the SMC material and AFM structure, 3D Finite Element Analysis (FEA) was carried out for accurate prediction of performance and extensive simulation results were provided. Higher fill factor up to 70% was achieve by compacting the pre-formed coils on a bobbin before sliding onto the tooth for final assembly, which offered a significant improvement in performance. AC winding loss analysis was performed due to open-slot stator winding configuration and the higher frequency of operation resulting in skin-depths of the same order of size as the typical conductor diameters. A method of AC winding loss reduction was introduced using a single steel lamination sheet to shield the windings from stray fields due to the open-slot stator construction which encourage an elevated AC loss at AC operation. Moreover, this approach is easy to implement for this machine topology and does not require the use of more complex twisted and Litz type conductors. To validate the 3D FEA, a prototype machine was built which ultimately resulted in 6 machines being tested without and with steel lamination sheet during this PhD. The measured result which includes the back EMF, full load voltage, torque, power and losses are thoroughly presented and agreed with the 3D FEA very well. Depending on lamination type, it is shown that the AC winding loss reduced by up to 48.0%, total loss reduced by up to 31.7%, this method has disadvantages of minor reduction of up to 3.5%, 5.8% and 2.8% in the peak back EMF, torque and output power respectively. The efficiency has increased by up to 10.3%. The research studies signify the viability of designing and producing a highly efficient AFM with SMC and has the potential for mass production, this thesis makes significant contribution by implementing a simple novel method for AC winding loss reduction using steel lamination sheet to shield the stray flux due to open-slot stator winding construction.The Petroleum Technology Development Fund (PTDF) Nigeria and NASRDA-CBS

Life cycle environmental and economic impact assessment of pollution mitigation strategies implemented in European pig production systems

Ph. D. Thesis.Pig production systems are significant contributors to environmental impacts arising from livestock and with the increasing demand for pork meat, their environmental footprint cannot be neglected. Many emerging technologies and alternative farm management practices have the potential to improve their environmental performance. However, the implementation of such practices is not always economically viable. Furthermore, their pollution mitigation potential can be sensitive to climate change and geographic variability. The aim of this thesis was to develop a whole-farm environmental abatement cost framework, able to evaluate the environmental and economic performance of pollution mitigation strategies from a life cycle perspective, while accounting for interactions between system components, climate change and spatial variability. To fully understand and evaluate the environmental impacts associated with European pig production, a whole-farm, environmental Life Cycle Assessment (LCA) was developed on a typical Danish, integrated pig farming system. Through this model, potential environmental impact hotspots were identified related to pig housing and manure management. The abatement potential of a range of housing and manure management related pollution mitigation strategies was then evaluated. The results of this analysis showed that anaerobic digestion of slurry and in-house slurry acidification can significantly reduce the system environmental impact for a great range of impact categories. Farm profitability was then evaluated through scenarios that simulated the implementation of the proposed pollution mitigation strategies, to determine their cost-effectiveness as stand-alone investments and through their combined implementation. For this purpose, an environmental abatement cost framework was developed by integrating the environmental LCA with a whole-farm economic model that considered capital costs, operating costs and all potential revenue streams. Anaerobic digestion of slurry was the most cost-effective strategy overall, achieving great environmental impact reductions while generating revenue and therefore increasing farm profitability. The environmental abatement cost framework was then used to investigate the mitigation potential of two pig-cooling strategies that aim for ammonia emission reductions in a Swedish pig-fattening unit. Moreover, the framework was integrated with data on projected climate change for Sweden to evaluate the resilience and cost-effectiveness of these strategies against ambient temperature increases. Both pig-cooling methods effectively mitigated heat stress related effects on animal performance, and significantly reduce system environmental impact, while improving farm profitability even under an intermediate climate change scenario. Finally, the effects of geographic variability on the assessment of potential environmental and economic implications associated with the implementation of alternative manure management strategies in Danish pig farming systems were investigated. To achieve this, Geographical Information System (GIS) data and methods were integrated along with the environmental abatement cost framework. In doing so, spatially explicit environmental impact characterisation factors, regional policies that concern pig farming near nature-sensitive areas and agglomeration effects on the economy of the farm were taken into account. The analysis revealed significant effects of location on the cost-effectiveness of several environmental abatement strategies considered. The methodologies developed and demonstrated in this thesis have the potential to guide decision making regarding farm investments that aim to improve system sustainability in a cost-effective manner.Newcastle University, Department for Environment, Food and Rural Affairs (DEFRA). SusAn, an ERA-Net Sustainable Animals co-funded research and innovation programme, European Union's Horizon 202

A Lipopolysaccharide (LPS) inhalation model to characterise divergent innate cellular responses and presence of alveolar leak, early in the course of acute lung inflammation

M. D. Thesis.Acute respiratory distress syndrome (ARDS) is a common condition presenting to the intensive care unit (ICU) and is associated with high morbidity and mortality. Experimental models in humans using bacterial lipopolysaccharide (LPS, delivered by nebulised inhalation or bronchial instillation) create reproducible acute lung inflammation and can be used to model early stages of the pathological process leading to ARDS. A significant body of evidence already exists from animal and human studies suggesting LPS inhalation results in rapid release of pro-inflammatory cytokines and movement of innate immune cells (neutrophils and monocytes) into the alveolar space. The functional status of neutrophils in response to this stimulus is largely unknown, based on circumstantial evidence provided by predominant cytokines, chemokines and cell surface protein expression. Most studies rely on invasive assessment of the alveolar space using bronchoalveolar lavage (BAL), and imaging modalities have been poorly explored in LPS respiratory models. This thesis aimed to test the hypothesis that, following inhalation of LPS, neutrophils circulating within peripheral blood increase their capacity for phagocytosis and generation of reactive oxygen species (ROS), and that dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) detects early increases in pulmonary vascular permeability. Forty-nine healthy human volunteers were recruited to an LPS inhalation study. Volunteers underwent inhalation of 60μg of LPS or Saline via a nebuliser dosimeter, with peripheral blood sampling. A subset underwent DCE MRI scans and bronchoscopy with BAL. Functional assays of phagocytosis and respiratory burst activity were performed on isolated neutrophils from blood. Neutrophils demonstrated a trend towards increased phagocytosis following LPS inhalation (change from baseline of 3.6% versus 1.2% in control subjects, p=0.058). This was not supported by any change in respiratory burst activity or flow cytometry assessment of cell surface protein expression. Analysis of DCE MRI of the lungs proved difficult and was complicated by significant artefact from surrounding structures and respiratory motion. In conclusion, LPS inhalation did not significantly affect phagocytosis or respiratory burst activity of neutrophils in the systemic circulation. DCE MRI was unable to detect changes in vascular permeability following LPS inhalation above the background noise

Elucidating the molecular drivers of prostate development using iPSC-derived organoids

PhD ThesisProstate cancer (PCa) is one of the leading causes of death among men in developed countries. Advances in uncovering the mechanisms of this disease have in part been hampered by the absence of a suitable human model that incorporates the complexity and variability of the disease. Inherent limitations of current models have prevented a complete understanding of PCa. Recently, patient-derived prostate organoids have emerged as an additional tool to complement current models. However, the process of prostate organoid generation using primary tissue can be inefficient. To overcome this and other limitations of current prostate organoid methodologies, our group developed an alternative method to produce prostate organoids using induced pluripotent stem cells (iPSCs). However, the process of prostate differentiation is complex and has yet to be fully elucidated. This research focused on optimizing the in vitro conditions of iPSC differentiation to prostate organoids, with a focus on using neonatal seminal vesicle mesenchyme (SVM) to induce prostate specification. The optimal culture conditions to produce prostate organoids were established and methods to maintain and analyse organoids were standardized. Organoids generated were composed of luminal, basal, and stromal cells, with rare neuroendocrine and stem cells. Additionally, we sought to elucidate the molecular drivers of prostate induction through RNA-sequencing analyses of the early rat prostate and inductive SVM. We were able to uncover candidate genes enriched in the inductive mesenchyme that may be involved with prostate specification. We were also able to identify genes and pathways in the epithelium that are likely responsible for responding to cues from the mesenchyme, leading to prostate differentiation. The candidates found in this research can be evaluated for their ability to improve iPSCs to prostate differentiation, which may eliminate the need for rodent mesenchymal tissue in this model. Furthermore, the datasets generated in this research can be further interrogated to better understand the reactivation of developmental genes in adulthood, leading to PCa

The impact of corporate governance on major shareholdings : the case of Saudi Arabia

PhD ThesisThe aim of this thesis is to examine whether the Corporate Governance (CG) structure in potential investee companies in Saudi Arabia has an impact on major shareholders choices of shares. Scholars argue that good CG practices provide investors with more confidence to invest their wealth in capital markets especially in developing countries (McKinsey, 2000). Saudi Arabia embraces unique cultural, economic, social, religious settings and is characterised with a prevalent presence of major shareholders in the capital market that is accompanied by allegedly weak legal settings, which was observed after the infamous collapse of the Saudi capital market in February 2006 (Ramady, 2010; Al-Nodel and Hussainey, 2010; Al-Matari, Al-Swidi and Fadzil, 2012). In order to investigate the impact of corporate governance on major shareholdings in the Saudi capital market, a full review of the CG evolution in Saudi Arabia is presented and two sets of questions are identified to achieve the objectives of this thesis. To address the research questions, this thesis employs triangulation (i.e., mixed methods, quantitative and qualitative) and embraces agency theory as main theoretical framework. The quantitative assessment is performed using a panel data analysis of 97 non-financial listed companies in the Saudi capital market over the period from 2013 to 2017 (485 observations). The qualitative assessment is performed by conducting semi-structured interviews with fifteen participants of different categories of major shareholders within the Saudi capital market. Overall, the regression analysis has shown that total major shareholdings have a significant negative relationship with CG score. Some interviewees expressed similar views toward such mechanisms as they are believed to be responsible for the limitation of their power over investee firms. The results of regression analysis to each category of major shareholders have revealed that the only categories that are significantly related to CG is wealthy families (negative) and wealthy individuals (positive), which is also supported by the findings of the qualitative assessment. The qualitative assessment of the rest of major shareholders categories have provided mixed results concerning CG preferences. Few interviewees believe that some parts of CG structure of investee firms play a role during the decision-making of their investments. On the other hand, most interviewees have revealed that CG in general is not taken into consideration when making investment decisions. This explains the insignificant relationship between CG and most categories of major shareholders revealed by the regression analysis.The government of Saudi Arabia and Imam Abdulrahman Bin Faisal Universit