The use of treosulfan in conditioning for haematopoietic stem cell transplantation in children with primary immunodeficiency

Ph. D. Thesis.Primary Immunodeficiencies (PIDs) are inherited disorders that lead to defects in the development and/or function of the immune system. The number of disorders that can be treated by haematopoietic stem cell transplantation (HSCT) has increased rapidly with the advent of next generation sequencing. The methods used to transplant children with PID have improved dramatically over the last 20 years. The introduction of reduced toxicity conditioning is an important factor in the improved outcome of HSCT. Treosulfan has myeloablative and immunosuppressive properties, enabling engraftment with less toxicity than traditionally used doses of busulfan. The use of treosulfan in conditioning prior to HSCT for children with PID is reported in this thesis. Six published works are presented. The first 2 provide background with up to date information on HSCT and conditioning regimens in children with PID. The increased use of low toxicity treosulfan-based combinations is demonstrated in published paper PP3 which is the largest published series to date of patients with non-malignant disorders who received treosulfan-based conditioning across Europe. The place of treosulfan in conditioning patients specifically with Chronic Granulomatous Disease from centres worldwide is presented in PP4. Close collaboration with Great Ormond Street Hospital, London has led to rigorous monitoring and step by step improvements in the approach to transplant using treosulfan, published in Supplementary paper 1, followed by PP5 and culminating in a prospective pharmacokinetic study presented in PP6, which is the first study to demonstrate an association with high area under the concentration curve (AUC) and increased mortality, and low AUC and poor engraftment. For each manuscript I present an overview of the study, what was known before, and what the study added to the literature, my contribution to the work and a short discussion of the strengths and limitations. Treosulfan has been established as a safe and effective agent for conditioning children with PID prior to HSCT. It is firmly incorporated into the conditioning guidelines of the Inborn Errors Working Party of the European Society for Blood and Marrow Transplantation. The works presented in this thesis demonstrate the contribution that I have made to the field, and pave the way for future research. It is likely that individualized dosing, not just of treosulfan, but of all agents used in conditioning regimens, will be developed and implemented. This will lead to a reduction in unwanted variability in drug exposure, leading to more predictable and adjustable exposure, and improved outcome of HSCT, with fewer late adverse effects and improved quality of life. Such conditioning regimens can be used as the basis to study the need for additional agents in certain disorders, the dosing of individual cellular components within grafts and effects of adjuvant cellular or immunotherapy post-transplant

Cartographies of Heritage : Mapping the Interpretation of Landscape

Ph. D. Thesis.This thesis critically assesses the capabilities of data visualisation as a medium for effectively presenting and communicating fuzzy data, exploring cartographic methods as an effective form of knowledge communication. It considers how data visualisation can be used to explore landscape themes, specifically by integrating Geographic Information Systems (GIS) to represent and analyse qualitative data for understanding cultural heritage landscapes. Using heritage as a key geographical theme, the thesis considers how individuals place ‘value’ onto locations by reviewing theories of landscape aesthetics as a way of conceptualising landscape recognition. By utilising GIS, the thesis devises a mixed-methods approach to map interpretations and responses to heritage landscapes, developing techniques to enable the visualisation of landscape responses through forms of digital cartography. The methodology is designed to be completed in two separate stages. The first stage involves the collection of categorical and quantifiable data through identified research methods. The second stage requires utilising the empirical data collection to create data visualisation and subsequent maps as evidence of the possibility to deploy qualitative cartographies. Consequently, this thesis shows that cartographic representations can interrogate the relationships between people and place using mixed methods through a qualitative GIS approach. Whether these are part of a series of ongoing innovations, as unique stand-alone maps or as complimentary and supplementary methods of visualisation, data representations can effectively communicate people's experiences with or interpretations of landscapes. Data graphics and cartographic representations can be used alongside or in tandem to one another as part of the same visualisation, to create new innovative forms of data visualisation for interrogating and deciphering the complexities between people and place.Economic and Social Research Council (ESRC), North East Doctoral Training Centre (NEDTC

A longitudinal study of cultural identity shifts and social contact of Postgraduate student sojourners at a British university

PhD ThesisThis study explores the cultural identity changes of student sojourners in cross-cultural transition and examines the relationship between cultural identities and social contact. A longitudinal mixed methods research design, using semi-structured interviews (N=18) and surveys (N=84), was employed. The study was conducted at a British higher education institution over 16 months, encompassing the re-entry phase, and participants were students enrolling in postgraduate taught programmes. The research employed the Integrative Theory of Communication and Cross-cultural Adaptation of Kim (2001) and the Acculturation model of Berry (2005) to argue that cultural identities are bidimensional, consisting of home and host cultural identification. Furthermore, their construction are suggested to be based on two components: emotional attachment and the acknowledgement of cultural membership (Lustig and Koester, 2003; Ting-Toomey and Chung, 2005). Findings showed that in addition to the two components mentioned above, the cultural identities of student sojourners were influenced by place attachment and the self-reflection of behaviours. After the sojourn, most participants became more aware of their identities. They developed a stronger sense of identification with home cultures and ‘foreign’ cultures, and usually referred to these as ‘mixed’ cultural identities. Shifts in cultural identities occurred in dynamic ways and were influenced by contact patterns, the ‘international’ contexts in higher education, adaptation and adjustment. Although student sojourners often regarded non-co-national internationals as the most popular contact source, grouping of students based on regions of origins and nationalities were frequently reported. Contact with host nationals remained limited throughout the sojourn. Based on these findings, some modifications to the theories about cultural identities during cross-cultural transition, such as Acculturation model (Berry, 2005), were made to enhance their applicability to the case of student sojourners. A theoretical framework which integrates the cultural identification process, social contact and adaptation is introduced. Finally, some suggestions and practical implications for higher education institutions and educators to improve postgraduate students' overseas stay and reduce social grouping are also presented. Overall, the study offers an enhanced understanding about the cultural identities of student sojourners and provides researchers in the intercultural communication field and higher education educators with helpful information of the students’ adjustment and socialising experiences

Preparation and applications of polymer immobilised ionic liquids for electrochemical applications

PhD ThesisChapter 1 introduces and explores the concept of ionic liquids and polymer-immobilised ionic liquids as functional materials for alkaline anion exchange fuel cells (AAEMFCs) and catalysis. Chapter 2 details the preparation of a norbornene-based monomer library which has been used to prepare and test a series of polymer formulations for physical and electrochemical testing, with the aim of identifying suitable membranes for fuel cell and related electrochemical technology. The most conductive AAEMs prepared in utilised a diethylene glycol (DEG) cross-linker and had an ionic conductivity of 27.2-31.0 mScm-1 at 80 °C. This chloride conductivity corresponds to a hydroxide conductivity of 71-81 mScm-1 at 80 °C – these values were estimated using an experimentally tested ion mobility conversion factor. This chapter also covers the development of a suitable accelerated stability study for anion exchange membrane degradation in hydroxide conditions monitored by NMR spectroscopy. The two ionic monomers prepared were found to be chemically stable in alkaline conditions at 80 °C over 696 hours. Polyoxometalate poly(ionic liquid) phase catalysts (POM@PIILP) were prepared utilising a styrene polymer architecture in chapter 3 with the aim of preparing new catalysts for biomass transformation. An initial screening was carried out in order to identify the most efficient catalysts to take forward and optimise in terms of catalyst loading, operating temperature and catalyst recyclability. Lead catalysts were identified and were capable of 90-99% conversion with respect to the substrate, furfuryl alcohol, and achieved 100% selectivity to product, nbutyl levulinate, in 2 hours. However, issues with catalyst recyclability were encountered; preliminary poisoning experiments suggested that deactivation of the surface reduced catalytic activity. Chapter 4 introduces a new technology to expand upon the Doherty’s group expertise in ionic liquid synthesis in the form of materials suitable for 3D printing by digital light processing technology. In this chapter imidazolium-based ionic liquid monomers were prepared, and suitable acrylate-based cross-linkers were used to formulate photopolymer resins. Screening of these resins was carried out using a bespoke UV-LED system and then suitable materials were 3D printed using a digital light processing (DLP) UV photopolymer printer. The resultant ion exchange membranes were then assessed in terms of their ionic conductivity, ion exchange capacity and mechanical integrity as anion exchange membranes in a similar manner to the membranes prepared in Chapter 2. The polymers were found to have a chloride ionic conductivity of 19-31 mScm-1 at 80 °C, which equates to an estimated hydroxide conductivity of 50-81 mScm-1 .Leverhulme Trust Research Project Grant

Calm Displays and Their Applications : Making Emissive Displays Mimic Reflective Surfaces Using Visual Psychophysics, Light Sensing and Colour Science

Ph. D. Thesis.Our environment is increasingly full of obtrusive display panels, which become illuminating surfaces when on, and void black rectangles when off. Some researchers argue that emissive displays are incompatible with Weiser and Seely Brown's vision of "calm technology", due to their inability to seamlessly blend into the background. Indeed, Mankoff has shown that for any ambient technology, the ability to move into the periphery is the most relevant factor in their usability. In this thesis, a background mode for displays is proposed based on the idea that displays can look like an ordinary piece of reflective paper showing the same content. The thesis consists of three main parts. In the first part (Chapter 4), human colour matching performance between an emissive display and reflective paper under chromatic lighting conditions is measured in a psychophysical experiment. We find that threshold discrimination ellipses vary with condition (16.0×6.0 ΔEab on average), with lower sensitivity to chroma than hue changes. Match distributions are bimodal for some conditions. In the second part (Chapter 5), an algorithm enabling emissive displays to look like reflective paper is described and evaluated, giving an average error of ΔEab = 10.2 between display and paper. A field study showed that paper-like displays are more acceptable in bedrooms and that people are more likely to keep them always on than normal displays. Finally, the third part (Chapter 6) concerns the development and four-week trial of a paper-like display application. Using the autobiographical design method, a system for sharing bedtime with a remote partner was developed. We see that once unobtrusive, display systems are desired for use even in spaces like bedrooms. Paper-like displays enable both emerging and existing devices to move into the periphery and become “invisible”, and therefore provide a new building block of calm technology that is not achievable using simple emissive displays

Transitioning power distribution grid into nanostructured ecosystem : prosumer-centric sovereignty

PhD ThesisGrowing acceptance for in-house Distributed Energy Resource (DER) installations at lowvoltage level have gained much significance in recent years due to electricity market liberalisations and opportunities in reduced energy billings through personalised utilisation management for targeted business model. In consequence, modelling of passive customers’ electric power system are progressively transitioned into Prosumer-based settings where presidency for Transactive Energy (TE) system framework is favoured. It amplifies Prosumers’ commitments into annexing TE values during market participations and optimised energy management to earn larger rebates and incentives from TE programs. However, when dealing with mass Behind-The-Meter DER administrations, Utility foresee managerial challenges when dealing with distribution network analysis, planning, protection, and power quality security based on Prosumers’ flexibility in optimising their energy needs. This dissertation contributes prepositions into modelling Distributed Energy Resources Management System (DERMS) as an aggregator designed for Prosumer-centered cooperation, interoperating TE control and coordination as key parameters to market for both optimised energy trading and ancillary services in a Community setting. However, Prosumers are primarily driven to create a profitable business model when modelling their DERMS aggregator. Greedy-optimisation exploitations are negative concerns when decisions made resulted in detrimental-uncoordinated outcomes on Demand-Side Response (DSR) and capacity market engagements. This calls for policy decision makers to contract safe (i.e. cooperative yet competitive tendency) business models for Prosumers to maximise TE values while enhancing network’s power quality metrics and reliability performances. Firstly, digitalisation and nanostructuring of distribution network is suggested to identify Prosumer as a sole energy citizen while extending bilateral trading between Prosumer-to- Prosumer (PtP) with the involvements of other grid operators−TE system. Modelling of Nanogrid environment for DER integrations and establishment of local area network infrastructure for IoT security (i.e. personal computing solutions and data protection) are committed for communal engagements in a decentralise setting. Secondly, a multi-layered Distributed Control Framework (DCF) is proposed using Microsoft Azure cloud-edge platform that cascades energy actors into respective layers of TE control and coordination. Furthermore, modelling of flexi-edge computing architecture is proposed, comprising of Contract-Oriented Sensor-based Application Platform (COSAP) employing Multi-Agent System (MAS) to enhance data-sharing privacy and contract coalition agreements during PtP engagements. Lastly, the Agents of MAS are programmed with cooperative yet competitive intelligences attributed to Reinforcement Learning (RL) and Neural Networks (NN) algorithms to solve multimodal socio-economical and uncertainty problems that corresponded to Prosumers’ dynamic energy priorities within the TE framework. To verify the DERMS aggregator operations, three business models were proposed (i.e. greedy-profit margin, collegial-peak demand, reserved-standalone) to analyse comparative technical/physical and economic/social dimensions. Results showed that the proposed TE-valued DERMS aggregator provides participation versatility in the electricity market that enables competitive edginess when utilising Behind-The-Meter DERs in view of Prosumer’s asset scheduling, bidding strategy, and corroborative ancillary services. Performance metrics were evaluated on both domestic and industrial NG environments against IEEE Standard 2030.7-2017 & 2030.8-2018 compliances to ensure deployment practicability. Subsequently, proposed in-house protection system for DER installation serves as an add-on monitoring service which can be incorporated into existing Advance Distribution Management System (ADMS) for Distribution Service Operator (DSO) and field engineers use, ADMS aggregator. It provides early fault detections and isolation processes from allowing fault current to propagate upstream causing cascading power quality issues across the feeder line. In addition, ADMS aggregator also serves as islanding indicator that distinguishes Nanogrid’s islanding state from unintentional or intentional operations. Therefore, a Overcurrent Current Relay (OCR) is proposed using Fuzzy Logic (FL) algorithm to detect, profile, and provide decisional isolation processes using specified OCRs. Moreover, the proposed expert knowledge in FL is programmed to detect fault crises despite insufficient fault current level contributed by DER (i.e. solar PV system) which conventional OCR fails to trigger

The value of multi-functional urban agriculture in creating sustainable cities

PhD ThesisChina's cities continue to expand rapidly and under severe challenge of sustainable urban development. The Chinese Government has decided to bring agriculture back into the city in a state-controlled way and to re-educate urban residents to enjoy agriculture activities in urban areas. This research explores the Chinese Government’s approach to new urban agriculture in China. It seeks to better understand and evaluate the impacts of multifunctional urban agriculture on sustainable urban development. The work is set within the context of China’s extremely rapid urbanization and concerns about pollution, poor lifestyles and an over-emphasis on manufacturing as the economic driver of growth. This thesis has presented a first attempt to redefine the term ‘urban’ in relation to urban agriculture, extending it to the urban core areas, desakota areas and exurban areas. In this way it suggests a new typology of urban agriculture in China, with a potentially broader range of objectives and possibilities that might normally be associated with the subject or practice. Taking Beijing as the case study city, this study selects 3 of its 16 districts: Chaoyang, Changping and Miyun representing core, desakota and exurban areas. The specific projects in these three districts are totally different, and together they represent the three levels in the model of Chinese new urban agriculture. Each level of model is informed and supported by case study of practical projects. These are: Government fully-owned large projects, Government-supported privately run projects and Folk Custom Villages. Data was collected from direct observation, documentation, archive, physical survey, interviews and questionnaires. This thesis found that the “Chinese” urban agriculture model, through three different types of projects, aims to make people rethink the role of agriculture and see it not simply as something undertaken by others in a rural area, nor as something simply to provide food. Rather, it can be something which enhances the urban experience, improves the urban environment, offers leisure facilities, engages people in traditional culture and provides a diverse range of employment and livelihood activities. A well planned modern agricultural production is required to create an agricultural environment with reasonable spatial layout to reduce pollution and to create aesthetically pleasing and sustainable landscapes. It can help urban agriculture ii integrate into the city system in a more sustainable way by reconnecting urban life and rural culture. This model, therefore, sets urban agriculture in a central role within planned urbanization. In summary, this thesis suggests that this model could become an important strategy for land use planning, urbanization and the sustainable development of Chinese cities, indeed, all cities, in the future. This study will be of interest to those scholars who are seeking to explore the Chinese urban agriculture as an effective method for land use in sustainable urban development

The Coroner in an Emerging Industrial Society: John Theodore Hoyle and Newcastle upon Tyne 1857-1885

Ph. D. Thesis.In this thesis I examine the life and work of the Victorian coroner for Newcastle upon Tyne, John Theodore Hoyle. Beginning with the nineteenth century description of the coroner as the People’s Judge, I establish a new definition of this epithet and use it as a lens with which to examine the life and work of a neglected but important branch of the Victorian judiciary. I use the character of the People’s Judge in examining the extent to which the personality, interests, and approach of a legally qualified coroner shaped the role of coroner in the community of Newcastle upon Tyne. I develop a biography of Hoyle from myriad small pieces of evidence. This is the central plank of the thesis and anchors the discussion and analysis which follows, in three broad areas: the dispute between medicine and the law in the coroner’s court; inquests into the deaths of infants; and inquests associated with industrial expansion. My research uses micro-history, legal history, and biography to draw together disparate sources relating to Hoyle’s life and work. My research establishes that the coroner, a judge who lived and worked in the community he served, is an integral part of the jigsaw in building a picture of the governance of Newcastle upon Tyne, an emerging industrial society, in the mid to late nineteenth century. The impact of Hoyle’s approach as a lawyer is central to appreciation of the coroner’s role. The thesis fills one of many gaps in knowledge of the nineteenth century coroner, and his work, by presenting a detailed study and analysis of the life and work of the coroner in the most northerly English town. My research has resulted in a database of material which will be used for further work and provides a template for such study.Northumbria Universit

Performance-efficient cryptographic primitives in constrained devices

PhD ThesisResource-constrained devices are small, low-cost, usually fixed function and very limitedresource devices. They are constrained in terms of memory, computational capabilities, communication bandwidth and power. In the last decade, we have seen widespread use of these devices in health care, smart homes and cities, sensor networks, wearables, automotive systems, and other fields. Consequently, there has been an increase in the research activities in the security of these devices, especially in how to design and implement cryptography that meets the devices’ extreme resource constraints. Cryptographic primitives are low-level cryptographic algorithms used to construct security protocols that provide security, authenticity, and integrity of the messages. The building blocks of the primitives, which are built heavily on mathematical theories, are computationally complex and demands considerable computing resources. As a result, most of these primitives are either too large to fit on resource-constrained devices or highly inefficient when implemented on them. There have been many attempts to address this problem in the literature where cryptography engineers modify conventional primitives into lightweight versions or build new lightweight primitives from scratch. Unfortunately, both solutions suffer from either reduced security, low performance, or high implementation cost. This thesis investigates the performance of the conventional cryptographic primitives and explores the effect of their different building blocks and design choices on their performance. It also studies the impact of the various implementations approaches and optimisation techniques on their performance. Moreover, it investigates the limitations imposed by the tight processing and storage capabilities in constrained devices in implementing cryptography. Furthermore, it evaluates the performance of many newly designed lightweight cryptographic primitives and investigates the resources required to run them with acceptable performance. The thesis aims to provide an insight into the performance of the cryptographic primitives and the resource needed to run them with acceptable performance. This will help in providing solutions that balance performance, security, and resource requirements for these devices.The Institute of Public Administration in Riyadh, and the Saudi Arabian Cultural Bureau in Londo

An exploration of the lived experiences of gender diverse young people in schools

D. App. Ed. Psy. ThesisThis thesis explores the lived experiences of gender diverse (GD) young people (YP) in schools. It comprises of four chapters: a Systematic Literature Review, a methodological and ethical critique, a piece of empirical research and a reflective synthesis. Chapter 1 This chapter reports on a Systematic Literature Review, synthesising five papers. It explores how transgender and cisgender YP’s experiences of education differ. All five of the studies explored found that transgender youth experience more risk factors than their cisgender peers. Furthermore, these experiences were found to be unique to transgender students when compared to non-heterosexual cisgender peers, with whom they are often linked. Chapter 2 This chapter provides a methodological and ethical critique of possible and relevant research designs and methods that have been employed in my empirical research. This includes a reflection on my positionality as a researcher and how the ontological and epistemological viewpoints I espouse have underpinned the methodological and ethical decisions I have made throughout my thesis. Chapter 3 While the exploration into the experiences of GD YP is a growing field within psychological and educational research, much of the current research available has explored the negative experiences faced by GD YP and the detrimental impact this has had on their outcomes both within school and into adulthood. This chapter reports an empirical research project involving two GD YP. It provides a qualitative exploration of participants’ experiences of education, exploring both positive and negative elements. Findings are discussed in relation to previous literature. Limitations and implications for schools, as well as for Educational Psychologists, are highlighted. Chapter 4 This chapter demonstrates what the work has meant to me as a practitioner and researcher, and what the next steps are for me as I become a fully qualified Educational Psychologist. It also explores some of the critical thinking processes I went through during my research journey and the challenges I faced particularly considering the COVID-19 pandemi