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“It’s rote learning, but it gets the mark” : exploring Scottish history teachers’ (dis)engagements with social justice education
No full textThe purpose of this study is to explore how secondary school history teachers in Scotland engage with social justice, if at all. In doing so, this study seeks to, more specifically, explore their understanding of social justice and social justice education (SJE) as well as how this understanding might impact upon their teaching practice. Further, this study seeks to explore what history teachers in the Scottish educational context see as their role in the classroom and how this might emerge in their reporting of their practice. Three instruments for data collection were used, including participant-created (1) identity charts and (2) Scottish Qualifications Authority (SQA) question annotations, and (3) semi-structured interviews. Reflexive Thematic Analysis (Braun & Clarke, 2019) and Narrative Inquiry (Clandinin & Connelly, 2000) were drawn upon to analyse the data. The flexible nature of Reflexive Thematic Analysis and storied nature of Narrative Inquiry allowed for the exploration of the nuanced and complex nature of each participant’s experiences. The findings suggest that there is a trend of using exams as a mechanism towards social justice, which leads to a status quo of a results-focused exam culture for some teachers in Scotland, reinforcing a contradiction or access paradox where teaching and learning revolve around exams as a way to access social mobility. In this way, what happens in the classroom is bound to exams and offers little or no opportunities to interrupt this cycle. The access paradox posits that by helping learners to access SQA qualifications, which are achieved through exams and are a dominant form of currency in the Scottish context, teachers help learners unlock opportunities within the confines of the existing educational system, without necessarily problematising or transforming it, and this, therefore, leads to perpetuating the value of SQA qualifications. However, if teachers deny learners access to SQA qualifications, they contribute to their marginalisation in a society that continues to place high value on SQA qualifications. Participants recognised that the status quo of a results-focused exam culture is problematic but placed blame on the system, claiming that there is nothing they can do about it other than work within it, and this indicates what they think their role is in the classroom: to teach to the test.The purpose of this study is to explore how secondary school history teachers in Scotland engage with social justice, if at all. In doing so, this study seeks to, more specifically, explore their understanding of social justice and social justice education (SJE) as well as how this understanding might impact upon their teaching practice. Further, this study seeks to explore what history teachers in the Scottish educational context see as their role in the classroom and how this might emerge in their reporting of their practice. Three instruments for data collection were used, including participant-created (1) identity charts and (2) Scottish Qualifications Authority (SQA) question annotations, and (3) semi-structured interviews. Reflexive Thematic Analysis (Braun & Clarke, 2019) and Narrative Inquiry (Clandinin & Connelly, 2000) were drawn upon to analyse the data. The flexible nature of Reflexive Thematic Analysis and storied nature of Narrative Inquiry allowed for the exploration of the nuanced and complex nature of each participant’s experiences. The findings suggest that there is a trend of using exams as a mechanism towards social justice, which leads to a status quo of a results-focused exam culture for some teachers in Scotland, reinforcing a contradiction or access paradox where teaching and learning revolve around exams as a way to access social mobility. In this way, what happens in the classroom is bound to exams and offers little or no opportunities to interrupt this cycle. The access paradox posits that by helping learners to access SQA qualifications, which are achieved through exams and are a dominant form of currency in the Scottish context, teachers help learners unlock opportunities within the confines of the existing educational system, without necessarily problematising or transforming it, and this, therefore, leads to perpetuating the value of SQA qualifications. However, if teachers deny learners access to SQA qualifications, they contribute to their marginalisation in a society that continues to place high value on SQA qualifications. Participants recognised that the status quo of a results-focused exam culture is problematic but placed blame on the system, claiming that there is nothing they can do about it other than work within it, and this indicates what they think their role is in the classroom: to teach to the test
Application of pharmacoepidemiological approaches to generate real-world evidence on the use and impact of metastatic colorectal cancer medicines
Full text linkIntroduction: Metastatic colorectal cancer (mCRC) is characterised by multiple treatment strategies. Randomised clinical trials are not always aligned with clinical practice, and greater use of real-world (RW) studies has been suggested to inform health care decisions by providing results that reflect RW practice.Methods: This thesis utilised multiple methods. First, a systematic review and meta-analyses (SRMA) of RW studies including mCRC patients treated with first-line (1L) systemic anti-cancer therapy (SACT) was conducted to explore the comparative safety and effectiveness, including overall survival (OS), progression free survival (PFS) and objective response of 1L mCRC SACTs. Second, a retrospective observational cohort study using linkage of routinely collected data of mCRC patients treated with 1L SACT in NHS GGC from 01/01/2015 to 31/12/2016 was performed to investigate the factors influencing selection of 1L mCRC SACTs, treatment pathways, and treatment outcomes including median OS (mOS) and time-to-next-treatment (TTNT) of mCRC patients. Results: Between 2015 and 2016, A total of 220 new mCRC SACT users were identified in NHS GGC, with 52.3% (N=115) of the patients treated with a doublet of FOLFOX or FOLFIRI, 22.3% (N=49) with 5FU, 19.5% (N=43) with cetuximab+FOLFIRI, and 5% (N=11) of patients treated initially with aflibercept+FOLFIRI. Treatment choices for 1L mCRC were made based on patients’ age and gender, tumour RAS status, and previous treatment response. The median overall survival (mOS) for these patients was statistically influenced by the initial mCRC SACT and the performance status. The combination of cetuximab+FOLFIRI demonstrated a statistically significant prolonged mOS compared to 5FU (HR 0.4 (95% CI 0.24-0.85) and the longest time to next treatment (TTNT (12.93 months (95%CI 5.85-15.25)). The SRMA also indicated an OS, PFS, and overall response rate benefit for bevacizumab+chemotherapy over chemotherapy alone with a statistically increased risk of non-haematological toxicities and a non-statistically significant increased risk for haematological toxicity.Conclusions: Real-world evidence can help understand the impact of mCRC SACT on evidence-based practice.Introduction: Metastatic colorectal cancer (mCRC) is characterised by multiple treatment strategies. Randomised clinical trials are not always aligned with clinical practice, and greater use of real-world (RW) studies has been suggested to inform health care decisions by providing results that reflect RW practice.Methods: This thesis utilised multiple methods. First, a systematic review and meta-analyses (SRMA) of RW studies including mCRC patients treated with first-line (1L) systemic anti-cancer therapy (SACT) was conducted to explore the comparative safety and effectiveness, including overall survival (OS), progression free survival (PFS) and objective response of 1L mCRC SACTs. Second, a retrospective observational cohort study using linkage of routinely collected data of mCRC patients treated with 1L SACT in NHS GGC from 01/01/2015 to 31/12/2016 was performed to investigate the factors influencing selection of 1L mCRC SACTs, treatment pathways, and treatment outcomes including median OS (mOS) and time-to-next-treatment (TTNT) of mCRC patients. Results: Between 2015 and 2016, A total of 220 new mCRC SACT users were identified in NHS GGC, with 52.3% (N=115) of the patients treated with a doublet of FOLFOX or FOLFIRI, 22.3% (N=49) with 5FU, 19.5% (N=43) with cetuximab+FOLFIRI, and 5% (N=11) of patients treated initially with aflibercept+FOLFIRI. Treatment choices for 1L mCRC were made based on patients’ age and gender, tumour RAS status, and previous treatment response. The median overall survival (mOS) for these patients was statistically influenced by the initial mCRC SACT and the performance status. The combination of cetuximab+FOLFIRI demonstrated a statistically significant prolonged mOS compared to 5FU (HR 0.4 (95% CI 0.24-0.85) and the longest time to next treatment (TTNT (12.93 months (95%CI 5.85-15.25)). The SRMA also indicated an OS, PFS, and overall response rate benefit for bevacizumab+chemotherapy over chemotherapy alone with a statistically increased risk of non-haematological toxicities and a non-statistically significant increased risk for haematological toxicity.Conclusions: Real-world evidence can help understand the impact of mCRC SACT on evidence-based practice
The sustainable livelihoods of informal artisan entrepreneurs in tourism : a case of Kenya
Full text linkThe tourism industry is a source of livelihood for many people as it creates employment and business opportunities. Nonetheless, the industry experiences many fluctuations and instabilities that threaten the livelihoods of those who depend on it. These threats are more intense for informal artisan entrepreneurs in tourism, who also grapple with enormous challenges in the informal sector despite their persistent work in the context. Thus, this exploratory research aims to understand how informal artisan entrepreneurs sustain their livelihoods while facing challenges in the informal sector and the tourism industry. The study uses the conceptual lens of the Sustainable Livelihoods Approach (SLA) and framework alongside the concepts of resilience, vulnerability and culture. It incorporates 51 telephone interviews with 32 artisans and 5 institutions in Kenya, conducted over two phases, and includes document analysis, field notes and researcher diaries. In doing so, the study draws key methodological considerations for conducting remote qualitative data collection and engaging with marginalised participants in Sub-Saharan Africa. The findings show that artisans experience constant challenges such as poverty, an indecent work environment, and inadequate institutional support. Nevertheless, their exposure to vulnerable conditions is paradoxically matched with resilience. The artisans’ resilience stems from their agency and socio-cultural structures, which have allowed them to combine different resources to sustain their livelihoods, cope with challenges, and persist in making handicrafts. Theoretically, the study creates a modified framework for sustainable livelihood analysis. It also challenges how resilience is conceptualised in sustainable livelihoods and entrepreneurship and suggests how it should be conceptualised. Relatedly, it draws insights into the paradoxical relationship between resilience and vulnerability. Hence, it contributes to the understanding of resilience in sustainable livelihoods. Notably, the study extends the body of knowledge on informal artisan entrepreneurs in tourism, who have proven unique in their characteristics and how they sustain their livelihoods.The tourism industry is a source of livelihood for many people as it creates employment and business opportunities. Nonetheless, the industry experiences many fluctuations and instabilities that threaten the livelihoods of those who depend on it. These threats are more intense for informal artisan entrepreneurs in tourism, who also grapple with enormous challenges in the informal sector despite their persistent work in the context. Thus, this exploratory research aims to understand how informal artisan entrepreneurs sustain their livelihoods while facing challenges in the informal sector and the tourism industry. The study uses the conceptual lens of the Sustainable Livelihoods Approach (SLA) and framework alongside the concepts of resilience, vulnerability and culture. It incorporates 51 telephone interviews with 32 artisans and 5 institutions in Kenya, conducted over two phases, and includes document analysis, field notes and researcher diaries. In doing so, the study draws key methodological considerations for conducting remote qualitative data collection and engaging with marginalised participants in Sub-Saharan Africa. The findings show that artisans experience constant challenges such as poverty, an indecent work environment, and inadequate institutional support. Nevertheless, their exposure to vulnerable conditions is paradoxically matched with resilience. The artisans’ resilience stems from their agency and socio-cultural structures, which have allowed them to combine different resources to sustain their livelihoods, cope with challenges, and persist in making handicrafts. Theoretically, the study creates a modified framework for sustainable livelihood analysis. It also challenges how resilience is conceptualised in sustainable livelihoods and entrepreneurship and suggests how it should be conceptualised. Relatedly, it draws insights into the paradoxical relationship between resilience and vulnerability. Hence, it contributes to the understanding of resilience in sustainable livelihoods. Notably, the study extends the body of knowledge on informal artisan entrepreneurs in tourism, who have proven unique in their characteristics and how they sustain their livelihoods
Investigating asthma aetiology and remedies in Saudi Arabia and the UK: Assessing the impact of indoor air pollution and healthcare expertise on prescription expenses, within the realm of public health
Full text linkPreface: This thesis presents a comprehensive exploration into the multifaceted aspects of asthma, particularly emphasizing the interplay between asthma and various environmental and societal factors, including the COVID-19 pandemic, indoor air pollution, and healthcare practices. The research is contextualized within the Kingdom of Saudi Arabia and the United Kingdom, providing a comparative perspective on global and regional healthcare challenges and responses. Chapter 1: Introduction to the Thesis The opening chapter sets the stage for the entire thesis by providing an in-depth overview of asthma. This section is meticulously structured to cover a broad spectrum of topics related to this chronic respiratory condition. It begins with a clear definition of asthma, laying the foundation for subsequent discussions. The chapter proceeds to delve into the epidemiology of asthma, providing a critical analysis of its prevalence and impact on different populations. This is followed by an exploration of the pathophysiology and causes of asthma, offering insights into the biological and environmental factors contributing to its development. The clinical picture and diagnosis of asthma are then comprehensively discussed, highlighting the symptoms and diagnostic procedures. Finally, the chapter concludes with a detailed examination of asthma treatment, encompassing various therapeutic approaches and management strategies. Chapter 2: The Indoor Air Pollution and Childhood Asthma in the Kingdom of Saudi Arabia The second chapter narrows the focus to the relationship between indoor air pollution and childhood asthma in the Kingdom of Saudi Arabia. This segment of the thesis commences with an introduction that sets the context for the research, followed by a justification of the study. The chapter adopts a systematic approach in its methodology, delineating the steps taken from identifying the research question to charting the data and reporting the results. The findings section presents a detailed analysis of the diagnosis of childhood asthma in relation to indoor pollution. The discussion synthesizes the findings, and the chapter concludes with remarks and recommendations for future studies, proposing a prospective cohort study. Chapter 3: Knowledge, Attitude, and Practices of Primary Healthcare Providers in Makkah Chapter three shifts the focus to the knowledge, attitude, and practices of primary healthcare providers in Makkah regarding the assessment and management of acute asthma. This segment begins with an introduction that outlines the objective of the study. The method section details the approach taken for the research, followed by a results and discussion section that interprets the findings. Chapter 4: Prescription Pattern for Asthma Medications in the UK In chapter four, the thesis transitions to an examination of the prescription patterns for asthma medications in the UK, covering a decade from 2011 to 2021. This analysis is particularly poignant in the context of the COVID-19 pandemic. The chapter begins with an introduction that sets the stage for a detailed discussion on the impact of the pandemic on asthma in the COVID era. The aims of the study are clearly outlined, followed by a comprehensive description of the methods used, including study design, data sources, and ethical considerations. The results section presents a thorough analysis of the prescription patterns. Chapter 5: Impact of Lockdown During COVID-19 Pandemic on Asthma Medication Utilization in the UK The fifth chapter addresses the impact of the COVID-19 lockdown on the utilization patterns of asthma medications in the UK. This chapter begins with an introduction that frames the study within the context of the pandemic's broader medical impacts, especially on asthma exacerbations and medication use. The methods section delineates the study design, data sources, and analysis approach. The results are then presented, followed by a comprehensive discussion that delves into the findings and their implications. Conclusion The thesis culminates with a set of references and appendices that supplement the research. The references section provides a comprehensive list of all the sources cited throughout the thesis, ensuring that the research is grounded in existing literature and scientific evidence. The appendices section includes supplementary materials that support the research findings, such as data tables, questionnaires, and additional analyses. In summary, this thesis offers a holistic and nuanced examination of asthma, a condition that affects millions worldwide. By analyzing various factors such as indoor air pollution, healthcare practices, and the impact of the COVID-19 pandemic, the research provides valuable insights into the management and treatment of asthma. The comparative analysis between the Kingdom of Saudi Arabia and the United Kingdom offers a unique perspective on the global and regional dimensions of asthma, making this thesis a significant contribution to the field of public health.Preface: This thesis presents a comprehensive exploration into the multifaceted aspects of asthma, particularly emphasizing the interplay between asthma and various environmental and societal factors, including the COVID-19 pandemic, indoor air pollution, and healthcare practices. The research is contextualized within the Kingdom of Saudi Arabia and the United Kingdom, providing a comparative perspective on global and regional healthcare challenges and responses. Chapter 1: Introduction to the Thesis The opening chapter sets the stage for the entire thesis by providing an in-depth overview of asthma. This section is meticulously structured to cover a broad spectrum of topics related to this chronic respiratory condition. It begins with a clear definition of asthma, laying the foundation for subsequent discussions. The chapter proceeds to delve into the epidemiology of asthma, providing a critical analysis of its prevalence and impact on different populations. This is followed by an exploration of the pathophysiology and causes of asthma, offering insights into the biological and environmental factors contributing to its development. The clinical picture and diagnosis of asthma are then comprehensively discussed, highlighting the symptoms and diagnostic procedures. Finally, the chapter concludes with a detailed examination of asthma treatment, encompassing various therapeutic approaches and management strategies. Chapter 2: The Indoor Air Pollution and Childhood Asthma in the Kingdom of Saudi Arabia The second chapter narrows the focus to the relationship between indoor air pollution and childhood asthma in the Kingdom of Saudi Arabia. This segment of the thesis commences with an introduction that sets the context for the research, followed by a justification of the study. The chapter adopts a systematic approach in its methodology, delineating the steps taken from identifying the research question to charting the data and reporting the results. The findings section presents a detailed analysis of the diagnosis of childhood asthma in relation to indoor pollution. The discussion synthesizes the findings, and the chapter concludes with remarks and recommendations for future studies, proposing a prospective cohort study. Chapter 3: Knowledge, Attitude, and Practices of Primary Healthcare Providers in Makkah Chapter three shifts the focus to the knowledge, attitude, and practices of primary healthcare providers in Makkah regarding the assessment and management of acute asthma. This segment begins with an introduction that outlines the objective of the study. The method section details the approach taken for the research, followed by a results and discussion section that interprets the findings. Chapter 4: Prescription Pattern for Asthma Medications in the UK In chapter four, the thesis transitions to an examination of the prescription patterns for asthma medications in the UK, covering a decade from 2011 to 2021. This analysis is particularly poignant in the context of the COVID-19 pandemic. The chapter begins with an introduction that sets the stage for a detailed discussion on the impact of the pandemic on asthma in the COVID era. The aims of the study are clearly outlined, followed by a comprehensive description of the methods used, including study design, data sources, and ethical considerations. The results section presents a thorough analysis of the prescription patterns. Chapter 5: Impact of Lockdown During COVID-19 Pandemic on Asthma Medication Utilization in the UK The fifth chapter addresses the impact of the COVID-19 lockdown on the utilization patterns of asthma medications in the UK. This chapter begins with an introduction that frames the study within the context of the pandemic's broader medical impacts, especially on asthma exacerbations and medication use. The methods section delineates the study design, data sources, and analysis approach. The results are then presented, followed by a comprehensive discussion that delves into the findings and their implications. Conclusion The thesis culminates with a set of references and appendices that supplement the research. The references section provides a comprehensive list of all the sources cited throughout the thesis, ensuring that the research is grounded in existing literature and scientific evidence. The appendices section includes supplementary materials that support the research findings, such as data tables, questionnaires, and additional analyses. In summary, this thesis offers a holistic and nuanced examination of asthma, a condition that affects millions worldwide. By analyzing various factors such as indoor air pollution, healthcare practices, and the impact of the COVID-19 pandemic, the research provides valuable insights into the management and treatment of asthma. The comparative analysis between the Kingdom of Saudi Arabia and the United Kingdom offers a unique perspective on the global and regional dimensions of asthma, making this thesis a significant contribution to the field of public health
Gender, loss, and memory : women’s experiences of deindustrialisation in the West of Scotland textile industry since 1970
Full text linkThe process of deindustrialisation has been intrinsically linked to male dominated industries such as coalmining, shipbuilding, and steelworks during the 1970s and 1980s. However, women have also experienced deindustrialisation, most prominently in the one sector in which they dominated - textiles. The industry experienced an intense period of deindustrialisation in the late 1990s with 40,000 textile jobs lost in Britain in 1999 alone. In this period, Scotland experienced over 3,000 job losses with Bairdwear closing their garment factories in Glasgow, Daks Simpson closing their factory in Larkhall, and Coats Viyella closing their garment factory in Alloa. Yet it is the case that the experience of the textile industry has remained relatively absent, in a British context, from the discussions around industrial communities’ experiences of deindustrialisation.Through the use of oral history testimony from women textile workers, this thesis critically assesses their working lives in the textile industry. In explores how women’s working lives were profoundly altered during the last third of the twentieth century as a result of the growth of automation and technology on the factory floor which limited their autonomy, deskilled their labour, and facilitated the downscaling of the industry in the 1980s and early 1990s. Moreover, the thesis critically examines the textile industry’s experience of intensive deindustrialisation during the late 1990s and early 2000s. It argues that the industry experienced trade-induced deindustrialisation, emanating from the phasing out of the protectionist Multi Fibre Arrangement which resulting in the significant offshoring of tens of thousands of textile jobs from Britain to the global South and eastern Europe. The thesis aims to move the analysis beyond a head count and contends with the deep-seated legacies of deindustrialisation, including how it is popularly conceived in the national consciousness, how it is represented in heritage institutions, and how it is reflected in cultural representations of working-class life in Scotland. Ultimately, the thesis advances the case that there remains significant work to be done to mainstream women’s experiences into the dominant conceptualisation of deindustrialisation.The process of deindustrialisation has been intrinsically linked to male dominated industries such as coalmining, shipbuilding, and steelworks during the 1970s and 1980s. However, women have also experienced deindustrialisation, most prominently in the one sector in which they dominated - textiles. The industry experienced an intense period of deindustrialisation in the late 1990s with 40,000 textile jobs lost in Britain in 1999 alone. In this period, Scotland experienced over 3,000 job losses with Bairdwear closing their garment factories in Glasgow, Daks Simpson closing their factory in Larkhall, and Coats Viyella closing their garment factory in Alloa. Yet it is the case that the experience of the textile industry has remained relatively absent, in a British context, from the discussions around industrial communities’ experiences of deindustrialisation.Through the use of oral history testimony from women textile workers, this thesis critically assesses their working lives in the textile industry. In explores how women’s working lives were profoundly altered during the last third of the twentieth century as a result of the growth of automation and technology on the factory floor which limited their autonomy, deskilled their labour, and facilitated the downscaling of the industry in the 1980s and early 1990s. Moreover, the thesis critically examines the textile industry’s experience of intensive deindustrialisation during the late 1990s and early 2000s. It argues that the industry experienced trade-induced deindustrialisation, emanating from the phasing out of the protectionist Multi Fibre Arrangement which resulting in the significant offshoring of tens of thousands of textile jobs from Britain to the global South and eastern Europe. The thesis aims to move the analysis beyond a head count and contends with the deep-seated legacies of deindustrialisation, including how it is popularly conceived in the national consciousness, how it is represented in heritage institutions, and how it is reflected in cultural representations of working-class life in Scotland. Ultimately, the thesis advances the case that there remains significant work to be done to mainstream women’s experiences into the dominant conceptualisation of deindustrialisation
Detection of galectin proteins using advanced raman rechniques
No full textGalectin-3 protein (Gal-3) has emerged as a potential indicator suitable for the prognosis of many diseases, such as heart failure, viral infection, kidney disease, tumour formation, etc, thus monitoring its expression could assist in clinical decision-making. This study focuses on the development of new diagnostic and imaging approaches for the detection of serum and cellular
Gal-3. Here, a label-free, rapid and cost-effective platform for Gal-3 detection is proposed based on specifically designed 3-mercaptopropyl β-D-lactoside-coated nanoparticles (AuML3) that present changes of surface plasmon resonance (SPR) band after interactions with Gal-3 protein. Surface modification of citrate gold nanoparticles with a lactose-containing ligand such as 3-mercaptopropyl β-D-lactoside (ML3) provides multiple binding areas for Gal-3 protein that enhance the protein-carbohydrate-binding affinities and increase the detection sensitivity. More specifically, the increase of Gal-3 concentration resulted in the dampening of the 530 nm extinction peak and the appearance of a second extinction band present at 700 nm, leading to 0.1 nM limit of detection (LoD). Additionally, the interactions of AuML3 nanosensors with a control protein such as bovine serum albumin (BSA) or with 10 nM of Gal-3 previously treated with lactose solution, that has high affinity towards Gal-3 did not display any SPR band shift verifying the selectivity of the AuML3 glycoconjugates against Gal-3 and the lack of significance of the non-specific interactions. Previous studies have shown that the interactions between multivalent proteins and SE(R)RS nanotags generate aggregates that lead to the formation of hotspots and enhancement of the SE(R)RS signal. Therefore, SE(R)RS advantages were exploited in designing a more sensitive approach based on AuCit nanoparticles functionalised with a Raman reporter such as MGITC and an ML3 ligand that interacts specifically with Gal- 3. More specifically, the interaction of the SERRS nanosensors with Gal-3 led to similar SPR changes as the label-free approach. Furthermore, the recognition of Gal-3 by the SERRS nanosensors resulted in colour changes of the solution from pink-red to purple and increased hydrodynamic diameter with increasing protein concentrations, indicating the formation of lactose-Gal-3 aggregates. We additionally demonstrated that the interaction of SERRS nanotags with Gal-3 enhanced the SERRS signal. However, a clear connection between the
detected SERRS signal and Gal-3 concentration was not possible due to the fluctuations caused by uncontrolled aggregation. We believe that the SERRS signal could potentially be quantitative with further optimisation of SERRS nanosensors. A variety of imaging techniques have been widely used in imaging biological samples to understand the underlying biochemistry of cells and tissues. Advanced bioorthogonal Raman labels have been employed in developing stimulated Raman spectroscopy (SRS) and Raman immunostaining to overcome some limitations of the current fluorescence tags used in
immunocytochemistry such as photobleaching and limited multiplexing capability. Here, a novel approach to immunofluorescence, called immuno-SRS microscopy, was designed to selectively detect Gal-3, through the reaction of biotinylated antibodies with alkyne-modified streptavidin-HRP. During the immuno-SRS staining the cells were first incubated with AntiGal-3 biotinylated antibodies and then stained with alkyne-modified streptavidin. The successful synthesis of alkyne-modified streptavidin was confirmed by UV-vis and Raman
spectroscopy. This approach allows the specific detection of intercellular Gal-3 proteins in various permeabilised cell lines, such as Michigan cancer foundation-7 (MCF-7), Henrietta Lacks (HeLa) and the human lung cancer cell line H1975, by demonstrating the breakthrough potential of alkyne tags for intracellular immune-labelling with high spatial resolution using rapid SRS imaging. These results displayed negligible background signal in off-resonance
frequency. Additionally, increasing the number of triple bonds in the polyyne chain of the alkyne tag led to alterations of the detected Raman shifts, which could lead to the simultaneous visualisation of different molecular species.
The designed alkyne-modified streptavidin tags were also implemented in alkyne-tag Raman imaging (ATRI) immunolabelling for the quantification of Raman intensity of the Gal-3 and α-tubulin population in the cellular, nuclei and cytoplasmatic areas. To our knowledge, this is the first example of ATRI immunolabelling based on particle-free alkyne-conjugates and more
conventional Raman techniques. The signal amplification achieved in this new method is based on the combination of streptavidin-HRP-conjugates, which increase the binding sites of strconjugates per antibody and produce bright Raman alkyne tags. Therefore, this study highlighted that ATRI immunolabelling offers a powerful tool for screening and diagnostic accuracy involving intracellular imaging and understanding of protein mechanisms and
metabolism in different cell types.Galectin-3 protein (Gal-3) has emerged as a potential indicator suitable for the prognosis of many diseases, such as heart failure, viral infection, kidney disease, tumour formation, etc, thus monitoring its expression could assist in clinical decision-making. This study focuses on the development of new diagnostic and imaging approaches for the detection of serum and cellular
Gal-3. Here, a label-free, rapid and cost-effective platform for Gal-3 detection is proposed based on specifically designed 3-mercaptopropyl β-D-lactoside-coated nanoparticles (AuML3) that present changes of surface plasmon resonance (SPR) band after interactions with Gal-3 protein. Surface modification of citrate gold nanoparticles with a lactose-containing ligand such as 3-mercaptopropyl β-D-lactoside (ML3) provides multiple binding areas for Gal-3 protein that enhance the protein-carbohydrate-binding affinities and increase the detection sensitivity. More specifically, the increase of Gal-3 concentration resulted in the dampening of the 530 nm extinction peak and the appearance of a second extinction band present at 700 nm, leading to 0.1 nM limit of detection (LoD). Additionally, the interactions of AuML3 nanosensors with a control protein such as bovine serum albumin (BSA) or with 10 nM of Gal-3 previously treated with lactose solution, that has high affinity towards Gal-3 did not display any SPR band shift verifying the selectivity of the AuML3 glycoconjugates against Gal-3 and the lack of significance of the non-specific interactions. Previous studies have shown that the interactions between multivalent proteins and SE(R)RS nanotags generate aggregates that lead to the formation of hotspots and enhancement of the SE(R)RS signal. Therefore, SE(R)RS advantages were exploited in designing a more sensitive approach based on AuCit nanoparticles functionalised with a Raman reporter such as MGITC and an ML3 ligand that interacts specifically with Gal- 3. More specifically, the interaction of the SERRS nanosensors with Gal-3 led to similar SPR changes as the label-free approach. Furthermore, the recognition of Gal-3 by the SERRS nanosensors resulted in colour changes of the solution from pink-red to purple and increased hydrodynamic diameter with increasing protein concentrations, indicating the formation of lactose-Gal-3 aggregates. We additionally demonstrated that the interaction of SERRS nanotags with Gal-3 enhanced the SERRS signal. However, a clear connection between the
detected SERRS signal and Gal-3 concentration was not possible due to the fluctuations caused by uncontrolled aggregation. We believe that the SERRS signal could potentially be quantitative with further optimisation of SERRS nanosensors. A variety of imaging techniques have been widely used in imaging biological samples to understand the underlying biochemistry of cells and tissues. Advanced bioorthogonal Raman labels have been employed in developing stimulated Raman spectroscopy (SRS) and Raman immunostaining to overcome some limitations of the current fluorescence tags used in
immunocytochemistry such as photobleaching and limited multiplexing capability. Here, a novel approach to immunofluorescence, called immuno-SRS microscopy, was designed to selectively detect Gal-3, through the reaction of biotinylated antibodies with alkyne-modified streptavidin-HRP. During the immuno-SRS staining the cells were first incubated with AntiGal-3 biotinylated antibodies and then stained with alkyne-modified streptavidin. The successful synthesis of alkyne-modified streptavidin was confirmed by UV-vis and Raman
spectroscopy. This approach allows the specific detection of intercellular Gal-3 proteins in various permeabilised cell lines, such as Michigan cancer foundation-7 (MCF-7), Henrietta Lacks (HeLa) and the human lung cancer cell line H1975, by demonstrating the breakthrough potential of alkyne tags for intracellular immune-labelling with high spatial resolution using rapid SRS imaging. These results displayed negligible background signal in off-resonance
frequency. Additionally, increasing the number of triple bonds in the polyyne chain of the alkyne tag led to alterations of the detected Raman shifts, which could lead to the simultaneous visualisation of different molecular species.
The designed alkyne-modified streptavidin tags were also implemented in alkyne-tag Raman imaging (ATRI) immunolabelling for the quantification of Raman intensity of the Gal-3 and α-tubulin population in the cellular, nuclei and cytoplasmatic areas. To our knowledge, this is the first example of ATRI immunolabelling based on particle-free alkyne-conjugates and more
conventional Raman techniques. The signal amplification achieved in this new method is based on the combination of streptavidin-HRP-conjugates, which increase the binding sites of strconjugates per antibody and produce bright Raman alkyne tags. Therefore, this study highlighted that ATRI immunolabelling offers a powerful tool for screening and diagnostic accuracy involving intracellular imaging and understanding of protein mechanisms and
metabolism in different cell types
Considerations for in-process ultrasonic phased array inspection and monitoring of fusion welding processes
No full textWelding is an integral part of manufacturing and plays an important role in manysectors such as transport, energy and defence. Recent global events including the Covid-19 pandemic and ongoing war in Ukraine have placed significant pressures and challenges on the global manufacturing sector. Furthermore, increased focus is being placed on a move towards net-zero operations in light of the climate crisis. Challenging environments are often catalysts for adaptation and innovation, which is exactly what has been seen within manufacturing sectors worldwide. Motivation to remain globally competitive within a changing global landscape has placed advanced manufacturing at the forefront of future investment plans. Many industrial sectors employ Non-Destructive Evaluation (NDE) as a means of ensuring the integrity of welded components post-build and throughout their service life. In recent years there have been increasing economic and industrial drivers for the development of real-time NDE delivered at the point of manufacture. Real-time inspection and monitoring of welding processes can help to reduce fabrication costs by detecting defects as they occur, enabling more efficient and cost-effective builds whilst also supporting the assurance of asset integrity throughout the component life cycle. This thesis presents significant advancements in the field of in-process ultrasonic inspection and monitoring of fusion welding processes. The challenges associated with deployment of ultrasonic NDE during fusion welding are non-trivial. Therefore, considerable research has been required to fully understand the extent of these challenges and enable the development of techniques to address and overcome them. As a result, a system capable of ultrasonic phased array inspection during fusion welding has been realised to allow the detection of defects as they occur, thus reducing rework, repair time and helping to delivering high-quality welds right, first time. For the first time, phased array ultrasonic testing has been used to successfully interrogate the molten weld pool during deposition of gas tungsten arc welds, further reducing defect detection time. There is also significant opportunity to leverage this technique for in-process control of welding processes to prevent and reduce defect occurrence.Welding is an integral part of manufacturing and plays an important role in manysectors such as transport, energy and defence. Recent global events including the Covid-19 pandemic and ongoing war in Ukraine have placed significant pressures and challenges on the global manufacturing sector. Furthermore, increased focus is being placed on a move towards net-zero operations in light of the climate crisis. Challenging environments are often catalysts for adaptation and innovation, which is exactly what has been seen within manufacturing sectors worldwide. Motivation to remain globally competitive within a changing global landscape has placed advanced manufacturing at the forefront of future investment plans. Many industrial sectors employ Non-Destructive Evaluation (NDE) as a means of ensuring the integrity of welded components post-build and throughout their service life. In recent years there have been increasing economic and industrial drivers for the development of real-time NDE delivered at the point of manufacture. Real-time inspection and monitoring of welding processes can help to reduce fabrication costs by detecting defects as they occur, enabling more efficient and cost-effective builds whilst also supporting the assurance of asset integrity throughout the component life cycle. This thesis presents significant advancements in the field of in-process ultrasonic inspection and monitoring of fusion welding processes. The challenges associated with deployment of ultrasonic NDE during fusion welding are non-trivial. Therefore, considerable research has been required to fully understand the extent of these challenges and enable the development of techniques to address and overcome them. As a result, a system capable of ultrasonic phased array inspection during fusion welding has been realised to allow the detection of defects as they occur, thus reducing rework, repair time and helping to delivering high-quality welds right, first time. For the first time, phased array ultrasonic testing has been used to successfully interrogate the molten weld pool during deposition of gas tungsten arc welds, further reducing defect detection time. There is also significant opportunity to leverage this technique for in-process control of welding processes to prevent and reduce defect occurrence
New approaches in iridium catalysis for sp3 hydrogen isotope exchange of amino acid and peptides
No full textHydrogen isotope exchange (HIE) reactions are exceptionally valuable to the pharmaceu�tical industry. The ability to incorporate deuterium or tritium atoms within drug candidate molecules at the late stages of synthesis has revolutionised the drug discovery process. Specifically, the Kerr group has carried out extensive studies using iridium-based com�plexes, which have emerged as some of the most active systems in the area to facilitate directed labelling processes. In a response to the pharmaceutical industry’s recent focus on drug candidates with increased sp3 character, the Kerr research team have been driven to explore hydrogen isotope exchange reactions of amino acids and peptide-based structures.The chemistry detailed within this PhD Thesis builds on the team’s experiments with ɑ-amino acids, and delivers a corresponding robust and efficient method for the HIE of β-amino acids. β-Amino acids have increased resistance to proteolytic cleavage and improved pharmacokinetic profiles therefore, a mild approach for the deuteration of β-amino acid motifs could aid the successful development of novel peptide therapeutics. Through exten�sive screening of various iridium(I) pre-catalysts and conditions, excellent deuterium in�corporations have been achieved across a range of protected β-amino acids under mild conditions (Scheme 1). By exploiting common amino acid protecting groups, selective label�ling was attained via a proposed 5-membered metallocyclic intermediate, achieving up to 99% incorporation even at challenging centres. Additionally, a selection of cyclic amino acid residues were also labelled including the antifungal antibiotic cis-pentacin. Further�more, the labelling process is stereoretentive, as confirmed by chiral HPLC studies.[graphic element - Scheme 1: Iridium-catalysed HIE of β-amino acids.]Additionally, preliminary studies demonstrated impressive incorporations in β-amino acid containing dipeptides including the labelling of challenging methine sites (Scheme 2). Further investigations confirmed that larger tri- and tetra- peptides were successfully deuterated following additional optimisation. Moreover, computational density functional theory (DFT) studies were carried out alongside experimental investigations to rationalise our findings throughout.[graphic element - Scheme 2: Iridium-catalysed HIE of small peptides.]Hydrogen isotope exchange (HIE) reactions are exceptionally valuable to the pharmaceu�tical industry. The ability to incorporate deuterium or tritium atoms within drug candidate molecules at the late stages of synthesis has revolutionised the drug discovery process. Specifically, the Kerr group has carried out extensive studies using iridium-based com�plexes, which have emerged as some of the most active systems in the area to facilitate directed labelling processes. In a response to the pharmaceutical industry’s recent focus on drug candidates with increased sp3 character, the Kerr research team have been driven to explore hydrogen isotope exchange reactions of amino acids and peptide-based structures.The chemistry detailed within this PhD Thesis builds on the team’s experiments with ɑ-amino acids, and delivers a corresponding robust and efficient method for the HIE of β-amino acids. β-Amino acids have increased resistance to proteolytic cleavage and improved pharmacokinetic profiles therefore, a mild approach for the deuteration of β-amino acid motifs could aid the successful development of novel peptide therapeutics. Through exten�sive screening of various iridium(I) pre-catalysts and conditions, excellent deuterium in�corporations have been achieved across a range of protected β-amino acids under mild conditions (Scheme 1). By exploiting common amino acid protecting groups, selective label�ling was attained via a proposed 5-membered metallocyclic intermediate, achieving up to 99% incorporation even at challenging centres. Additionally, a selection of cyclic amino acid residues were also labelled including the antifungal antibiotic cis-pentacin. Further�more, the labelling process is stereoretentive, as confirmed by chiral HPLC studies.[graphic element - Scheme 1: Iridium-catalysed HIE of β-amino acids.]Additionally, preliminary studies demonstrated impressive incorporations in β-amino acid containing dipeptides including the labelling of challenging methine sites (Scheme 2). Further investigations confirmed that larger tri- and tetra- peptides were successfully deuterated following additional optimisation. Moreover, computational density functional theory (DFT) studies were carried out alongside experimental investigations to rationalise our findings throughout.[graphic element - Scheme 2: Iridium-catalysed HIE of small peptides.
Developing an improved complaint management system through the use of text modelling techniques
Full text linkThis thesis investigates the integration of textual complaint data into customer churn prediction (CCP) models, addressing a critical gap in the intersection of service recovery and predictive analytics. While traditional CCP models primarily rely on structured variables, textual complaints encapsulate rich customer sentiments and behavioural signals that remain underutilised in churn modelling. This research, therefore, explores how advanced text representation techniques can enhance CCP models, bridging the gap between service failure recovery theories and data-driven predictive modelling.
Grounded in service recovery and customer relationship management (CRM) theories, this study evaluates a decision-support framework that incorporates textual complaints and structured variables to improve churn prediction. Using real-life customer complaint data from a UK-based data-driven product company, the research benchmarks traditional count-based text representations (e.g., TF-IDF) against modern embedding-based methods (e.g., word embeddings, Transformer models). Additionally, the study investigates data fusion techniques, examining their role in leveraging multimodal information for improved churn prediction.
Key findings reveal that:
1. Incorporating textual complaint data significantly enhances CCP models, confirming the value of textual analysis in understanding customer behaviours.
2. Word embedding models outperform TF IDF-based models in overall CCP performance, indicating a shift towards more sophisticated text representation techniques.
3. TF-IDF-based models perform better at predicting retained customers, while word embedding models excel in identifying churn instances, underscoring the importance of task-dependent model selection.
4. An ensemble approach combining count-based and latent feature representations improves retained case prediction but slightly decreases churn prediction accuracy, suggesting that model selection should align with specific business objectives.
5. Data fusion techniques play a crucial role in optimizing predictive accuracy, demonstrating the need for well-designed multimodal integration strategies.
6. Structured variables remain essential in CCP models, providing additional insights into customer retention dynamics.
This thesis advances both theoretical and practical understanding of customer churn prediction by demonstrating how textual complaint data can be strategically leveraged to enhance CCP models. It contributes to service recovery and predictive analytics literature by offering a data-driven approach to customer retention strategies, equipping businesses with more effective and intelligent service recovery mechanisms.This thesis investigates the integration of textual complaint data into customer churn prediction (CCP) models, addressing a critical gap in the intersection of service recovery and predictive analytics. While traditional CCP models primarily rely on structured variables, textual complaints encapsulate rich customer sentiments and behavioural signals that remain underutilised in churn modelling. This research, therefore, explores how advanced text representation techniques can enhance CCP models, bridging the gap between service failure recovery theories and data-driven predictive modelling.
Grounded in service recovery and customer relationship management (CRM) theories, this study evaluates a decision-support framework that incorporates textual complaints and structured variables to improve churn prediction. Using real-life customer complaint data from a UK-based data-driven product company, the research benchmarks traditional count-based text representations (e.g., TF-IDF) against modern embedding-based methods (e.g., word embeddings, Transformer models). Additionally, the study investigates data fusion techniques, examining their role in leveraging multimodal information for improved churn prediction.
Key findings reveal that:
1. Incorporating textual complaint data significantly enhances CCP models, confirming the value of textual analysis in understanding customer behaviours.
2. Word embedding models outperform TF IDF-based models in overall CCP performance, indicating a shift towards more sophisticated text representation techniques.
3. TF-IDF-based models perform better at predicting retained customers, while word embedding models excel in identifying churn instances, underscoring the importance of task-dependent model selection.
4. An ensemble approach combining count-based and latent feature representations improves retained case prediction but slightly decreases churn prediction accuracy, suggesting that model selection should align with specific business objectives.
5. Data fusion techniques play a crucial role in optimizing predictive accuracy, demonstrating the need for well-designed multimodal integration strategies.
6. Structured variables remain essential in CCP models, providing additional insights into customer retention dynamics.
This thesis advances both theoretical and practical understanding of customer churn prediction by demonstrating how textual complaint data can be strategically leveraged to enhance CCP models. It contributes to service recovery and predictive analytics literature by offering a data-driven approach to customer retention strategies, equipping businesses with more effective and intelligent service recovery mechanisms
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