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    5357 research outputs found

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

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    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

    A comparison of methods to assess diagnostic performance when using imperfect reference standards

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    Ph. D. Thesis.Background: Estimating the diagnostic accuracy (sensitivity and specificity) of a new medical test in the absence of a gold standard or perfect reference standard is a common problem in diagnostic accuracy studies. Failing to correct for this imperfection risks under- or overestimating the accuracy measures of the index test. Aim: To identify and compare methods employed to evaluate the diagnostic accuracy of medical tests in the absence of a gold standard. Methodology: A systematic review was conducted to identify methods employed to evaluate the diagnostic accuracy in the absence of a gold standard. Promising correction methods and latent class models were explored and compared using simulation studies and clinical datasets. Results: The methods identified from the systematic review were classified into four main groups: methods employed when there is a missing gold standard; when there are multiple imperfect reference standards; correction methods; and other methods such as the test positivity rate. Following the simulation studies undertaken to compare the correction methods, the Staquet et al method was found to outperform the Brenner method. Investigation of the latent class models alongside the analysis of a clinical dataset indicates that the assumptions made on the tests being evaluated affect the estimates obtained and clinical decisions. Given three conditionally dependent tests, the fixed effect model and random effect model via logit link tended to be preferred to the finite mixture model and random effect model via probit link because they are less impacted by the choice of priors. Conclusion: Many methods have been developed to estimate the diagnostic accuracy of a medical test in the absence of a gold standard. The choice of method employed depends on the varying assumptions or characteristics of the tests under investigation as this can affect the estimates obtained and the decisions made in practice.Newcastle University Research Excellence Award, the School of Mathematics, Statistics and Physics, the Health Economics Group in the Population Health Sciences Institute (previously known as the Institute of Health and Society), and the National Institute for Health Research, Newcastle In-Vitro Diagnostics Co-operativ

    Investigating techno-economic factors influencing the future value of energy storage technologies

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    PhD ThesisThe decarbonization of electricity networks, all over the world, has led to an increasing amount of renewable generation in the energy mix. Although renewable generators produce clean and eco-friendly energy, high-penetration levels of renewables could also impose techno-economic challenges to the grid caused by their intermittent and stochastic character, compromising not only the security of electricity networks but also their energy equity. Renewable Energy Generation (REG) Providers can support electricity networks to address these challenges by providing grid-services and applications using different solutions. Energy Storage (ES) Devices are a flexible, yet expensive, smart grid solution able to store amounts of energy at one instant for their later utilization. The main barrier for their widespread proliferation has been, however, the high investment costs required to acquire and install these devices. This research investigates the factors influencing the future value of Energy Storage Technologies. The strategy to tackle this aim is based on designing, developing and implementing a techno-economic framework that allows the assessment of ES devices at planning stage. The framework is comprised of various models to examine diverse factors contributing with the value of ES devices. The simulation results of these framework models determine the maximum revenue that REG Providers can obtain from using ES devices alongside with the ES sizing design to achieve these outcomes. The outcomes of this work show the value for REG providers of using ES devices to address multiple applications and to profit from different energy market, the benefits and drawbacks of applying ES technologies in mandatory and non-mandatory service schemes, the value of using ES devices in mutual operation with renewable generators, the advantages of selecting ES technologies, and the contributions that enhancing the technical and economic features of ES technologies have on the value. The findings from this research can facilitate the widespread deployment of ES devices by providing valuable information to REG providers and investors when considering investments in ES technologies, technology developers to prioritize areas of enhancement in ES device, policy makers and regulators to understand the end to end effects that current regulations might produce on the interested parties and selling companies to expand the range of ES devices and hybrid combinations to offer for customers

    The Development of Phenotypic Screening Methods for Drug Discovery in Mitochondrial Dysfunction

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    PhD ThesisThis project both develops and employs high throughput phenotypic screening in the mitochondrial dysfunction research space. Initially, mitochondrial proliferation was investigated as it has emerged as a potential therapeutic pathway of interest. Collaborative efforts with the small biotechnology company, Nanna Therapeutics, have resulted in the screening of millions of bacterial natural product extracts for mitochondrial proliferation. The current project develops a multi-stage assay pipeline for the further screening of the hits identified in the work conducted by Nanna Therapeutics. A total of 10 hit extracts were identified, each capable of inducing increases in multiple parameters associated with mitochondrial biogenesis, in human cell lines. Four of the hits were selected for further investigation, as a result of maximal mitochondrial density increases being achieved with the minimum dose - in comparison with the remaining hit population. Mutations affecting the assembly of mitochondrial complexes were also investigated in the project. Mitochondrial Complex I (CI) deficiency is the leading biological hallmark of mitochondrial disease. As such, a high throughput screen has been optimised for the identification of novel therapeutic agents for the rescue of CI deficiency. As a result of the screen optimisation process, the current project also demonstrates the activity of lead compound for CI deficiency rescue, MOA2. The developed CI immunofluorescent staining protocol was also applied to Mitochondrial Complex IV (CIV) and Mitochondrial Complex II. Successful optimisation of a quadruple immunofluorescent technique targeting CI, CII and CIV followed, which was used to further show novel effects of MOA2. This project has given rise to multiple outputs. This thesis details the development of a high throughput assay pipeline for the discovery of small molecules capable of inducing mitochondrial proliferation, identifying ten hits. It has also demonstrated the effects of mitochondrial biogenesis on mitophagy. Finally, the current project has developed a novel in vitro method for the assessment of mitochondrial complex deficiencies in cells using immunofluorescent staining, with potential applications to the mitochondrial disease diagnostic space with further validation

    The Role of Copy Number Variants in Severe Idiopathic Male Infertility

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    PhD ThesisVery few genetic variants are currently known to cause severe male infertility phenotypes in a dominant fashion. This is explained by an absence of cohorts of patient-parent trios, which impedes the study of this genetic inheritance model. It has been demonstrated that de novo copy number variants (CNVs) on chromosome Y cause severe male infertility, but up to now, such variants have not been identified on the autosomes. In this thesis, I used whole-exome sequencing (WES) in a large cohort of male infertility patient-parent trios to study the possible role of de novo and maternally inherited CNVs as causes of quantitative sperm defects. I also used the same method to identify likely pathogenic CNVs in two patients-only cohorts affected by quantitative as well as qualitative sperm defects. We identified several possibly causative de novo and maternally inherited CNVs, pointing us to novel candidate genes for male infertility. Moreover, my findings contributed to the identification of the first gene on chromosome X associated with a male infertility phenotype characterised by multiple morphological abnormalities of the sperm flagella. This study reveals unique insight into the genetic aetiology of severe male infertility. Also, it illustrates the value of WES as a tool for CNV detection and supports the increasing use of this genomic technique in the field of male infertility genetics

    Explaining recent heterogeneous glacier change in the Annapurna Conservation Area, central Himalayas

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    PhD ThesisSince the 1970s, Himalayan glaciers have been shrinking in area, losing mass and decelerating in conjunction with warming air temperatures. This has serious implications for regional water resources. However, recent glacier change has been spatially heterogeneous and significant uncertainty remains about the sources (e.g. supraglacial debris, glacial hypsometry, avalanche-contributing area) of this local variability in the Himalayan glacier response to climate change. This thesis aims to characterise recent glacier changes in the Annapurna Conservation Area (ACA) in central Nepal and identify the extent and sources of local variability in the glacier change signal across a range of spatial (regional-, glacier- and sub-glacier-scale) and temporal (decadal to hourly) scales. Results show widespread glacier area loss (8.5% between 2000 and 2014/15) and mass loss (-0.28 ± 0.24 m w.e. a-1 between 2000 and 2013/16) in the ACA. However, glacier changes were spatially variable, with distinct glacier responses observed between sub-regions in the ACA. Individual glacier change was also modulated by supraglacial debris and glacier hypsometry. However, glacier elevation and avalanche-contributing area only influenced glacier change in the northern part of the study region, indicating that the strength of local controls was not spatially uniform. This thesis also identified another source of glacier response variability in the ACA, of potentially very localised importance, through the documentation of the first surge-type glacier in the central Himalayas. Sabche glacier had a very short surge cycle (~10 years), which is hypothesised to be modulated by subglacial topography, a mechanism that is rarely documented in published literature. Lastly, field data from Annapurna South glacier showed that the temperature and thermal properties of supraglacial debris varied both seasonally and between debris profiles of different thickness, which in turn had an important influence on the timing and magnitude of ablation. Overall, this thesis demonstrates the scale of local glacier change variability in the ACA and shows that the sources of this variability are complex and far from uniform. This work helps to put bounds on the level of noise occurring in the Himalayan glacier change signal and what can be considered a ‘normal’ range of variability. This heterogeneity should be taken into consideration when predicting how Himalayan glaciers will respond to climate change, and the impact of these glacier changes on local communitiesIAPETUS NERC Doctoral Training Partnershi

    Attitudes to immigration in times of crisis: the influence of austerity, cuts, and media attention

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    Ph. D. Thesis.This thesis focuses on the role that government policy and media attention play in public perceptions of real or perceived threats from immigration. I present three empirical chapters which provide significant original contributions to the literature on the external influences over individual attitudes to immigration and hostility toward foreigners or minorities. This literature and the contribution of this thesis is explored in chapter two. Chapter three exploits the controversial ‘Hartz IV’ unemployment benefit reform in Germany in 2005 as a natural experiment for the impact of personal financial shocks on attitudes to immigration. Difference-in-differences analysis using individual-level panel survey data and fixed effects provides novel causal evidence that personal financial shocks in the form of a cut in benefit payments can lead to short-term increases in individual concerns about immigration. These results provide support for economic self-interest theories of attitudes to immigration, specifically the welfare strain hypothesis, where poorer natives believe immigrants will reduce their access to benefits. In chapter four, I examine the relationship between the UK austerity programme introduced in 2013 and hate crimes motivated by race or religion. I estimate the causal impact of greater losses from benefit reforms introduced in April 2013 in a local area on the level of racially or religiously motivated (RRM) crimes recorded by the police. Using a difference-in-differences method with continuously varying treatment intensity consisting of the estimated total loss (£) per working age adult from the reforms in each area and including fixed effects I show evidence that austerity had a positive causal influence on rising RRM hate crime. The effects are primarily apparent for ‘public fear, alarm or distress’ offences, while no such effect is found for non-hate related offences. These findings suggest that financial shocks at the community level can increase hostility toward minority groups and support sociotropic theories of the impact of increased scarcity of resources on intergroup conflict, prejudice, and hate crime. Chapter five explores how a genuine migration crisis may alter the relationship between media salience and attitudes to immigration. Using individual-level panel survey data and original data on the salience of immigration in the German media on each day of 2015 collected using Python web scraping techniques and Lexis Nexis records, I estimate a respondent’s exposure to immigration news using their interview date. Linear Probability iv Model estimates show a clear difference in the significance of levels of media attention on immigration concerns before and during the main peak of the migrant crisis. Across the full period of interview dates (March to October) and when focusing on a period before the peak of the crisis (April to May), media salience appears to have a positive effect on higher concerns about immigration in line with the literature. However when considering interviews that took place within the main rise and peak of the migrant crisis (June to September), I find that the largest rises in media salience in 2015 had no significant impact on increases in immigration concerns in the same period. These findings suggest that while the influence of media did increase concerns in 2015, it did not play a causal role in rises in concerns during the peak of the migrant crisis, and may have been crowded out by exposure to the crisis itself, or cumulative exposure to news about the migrant crisis. This thesis provides novel causal evidence of how reactions to economic and demographic crises affect individual attitudes to immigration. The findings presented in the three empirical chapters extend the literature on the influence of economic and demographic conditions on attitudes to immigration by considering their indirect impact through government policy and media reactions

    Modelling of Fine Chemical Manufacturing Effluent and Emissions: Implementation of Mathematical and Physical Models for Wastewater Management

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    Eng. D. Thesis.This thesis consists of a portfolio of four projects that investigates, and addresses challenges faced by fine chemical and pharmaceutical manufacturers based in the UK to achieve greater control of effluent and air emissions in an environment of tightening legislation. In part one of this research, a mathematical model based on modified continually stirred tank reactor (CSTR) in series equations was created using MATLAB and deployed as a standalone tool with graphical user interface (GUI) to allow non-experts to predict the concentration of substances through a complex plant effluent system and activated sludge wastewater treatment plant (WWTP). The model showed an average prediction accuracy to within 9% of the true value on-site when validated against a tracer compound. In Part two of the thesis, a 100 litre small-scale activated sludge wastewater treatment plant was designed and built to enable extended testing of treatment efficiency for potential new wastewater streams for a large-scale (2400 m3 reactor) plant, to reduce the risk of breaching site effluent consent limits or large scale microorganism poisoning. Plant variables and conditions required to maintain equivalent wastewater treatment performance from the large-scale to the small-scale plant were researched and found to include temperature, pH, dissolved oxygen (DO) concentration, hydraulic retention time (HRT) and solids retention time (SRT). The resulting pilot plant matched performance of the large-scale plant to within 12.8% of effluent chemical oxygen demand (COD) concentration. Long term treatment efficiency testing of a methylene-blue dye containing wastewater was conducted and shown to be satisfactory after a period of microorganism acclimation, where equivalent short-term lab respirometry testing had previously shown no digestion of the blue wastewater. In part three of this thesis, mathematical models were researched and developed in MATLAB to study prediction of the effluent chemical oxygen demand concentration of an activated sludge wastewater treatment plant. Existing methods of non-linear modelling using partial least squares (PLS) and artificial neural network (ANN) structures were investigated and compared against a newly proposed structure that replaces the linear inner regressor of the PLS algorithm with a combination of multiple neural networks (mNNPLS). The mNNPLS model showed an improved correlation coefficient (R2) of 0.855 between observed variables and predicted effluent chemical oxygen demand. In the final section of the thesis, a methodology was created for conducting consequence and risk modelling using DNV’s PHAST software to compliment the studies in parts one and two by allowing estimation of substance input concentrations to the effluent system from potential major accidents to aid emergency response planning and test the robustness of the effluent system. Sources for input data including individual and societal risk criteria are researched and presented along with techniques of scenario identification, results presentation and overall report format

    Investigation of the production, isolation and bioactivity of the rishirilide natural products including crystallographic studies

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    PhD ThesisThe emergence of antibiotic resistant pathogenic bacteria has created a growing demand for research into new antibiotics. Bacterial natural products, particularly from the genus Streptomyces, have historically provided the basis for many clinically used antibiotics. In this project we have examined a class of natural product polyketides from Streptomyces as potential new mode of action antibiotics. We have focussed our investigation on two polyketides, (-)-rishirilide A and (+)-rishirilide B, originally isolated from Streptomyces rishiriensis OFR-1056. Following optimisation of fermentation and isolation protocols, milligram quantities of both (-)-rishirilide A and (+)- rishirilide B were obtained from Streptomyces albus::cos4. (-)-Rishirilide A displays antibiotic activity against Gram-positive bacteria (MICs: S. aureus, 1.56 µg/mL; B. subtilis, 3.125 µg/mL). Mode of action investigations showed that treatment with (-)-rishirilide A results in the depolarization of the bacterial cell membrane (B. subtilis 168CA). This may be due to (-)- rishirilide A acting as an irreversible inhibitor through Michael addition with a thiol containing enzyme. Further work will involve the synthesis of chemical probes based on (-)-rishirilide A to identify target enzymes. Additionally, we have supported this work with a study into the high-throughput nanoscale crystallisation (ENaCt) of natural products for single crystal X-ray analysis. Using ENaCt we have examined the crystallisation of a range of natural products. Cannabidiol and rifampicin crystals were obtained, and single crystal X-ray diffraction analysis successfully performed.Indonesian Endowment Fund (LPDP

    Spatial modelling of transcription dynamics in bacterial gene regulatory networks

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    Ph. D. Thesis.In Synthetic biology, researchers can alter the DNA sequence of organisms such that the behaviour to specific inputs is predictable. Regulatory systems have been ‘hacked’ into doing computation, help with bio-production, aid in personalised medicine and providing highly specific sensors. A major bottleneck in current synthetic biology is that models fail to predict system behaviour reliably, causing recent progress to be reliant on the trial and error of model-assisted system designs. One of the reasons for the models to fail is the neglect of Spatial effects. While this neglect simplifies models, recent experimental data shows localised effects. This work shows that only the combination of 3D cytosol diffusion and the 1D sliding along the chromosome of transcription factors can explain localised effects; the modelling transcription factors initial sliding route after formation reproduces experimental results. However, one essential assumption for the model described above is the initial location of a functional transcription factor at the encoding gene. While the coupled transcription and translation in prokaryotes are experimentally verified and can lead to the localisation of Transcription Factor proteins, this localisation must be assumed to be transferred to the active dimer form to reproduce the experiment. To substantiate this assumption, this work expands the limited field of protein dimerisation. A new model is introduced to explain the localisation effect with an extra pathway we call Translation Mediated Dimerisation. Here, the partially formed transcription factors still undergoing translation are thought to meet and form a dimer while still constrained to the mRNA on the other end. Even if this occurs in a minority of events, this can drastically affect non-linear behaviour. This model allows utilisation of localised effects for the rational design of system dynamics otherwise unavailable, expanding the possibilities and increasing the efficiency of synthetic biolog

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