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Distributed leadership : teachers' perspectives
Get PDFThis study explores distributed leadership from the perspectives of teachers at different levels within a secondary school, (with the exception of the head teacher). Scottish Government policy is manifest in secondary education in the deployment of distributed leadership practices that seek to maximise output by harnessing the talents of the teaching staff. Aligning with neo-liberalist tendencies, there appears to be an ever-increasing migration of responsibility away from government agencies and into the hands of teachers. This is further evidenced by the prominence within policy of teachers' roles in relation to school improvement and an emphasis upon teachers' agency. The rhetoric used to promote distributed leadership includes notions of increased individual agency, equality, democracy, empowerment, inclusion and collegiality. Despite the above, contemporary theorists contend that distributed leadership remains an ambiguous concept. In order to explore what distributed leadership means to teachers operating within secondary education, this study seeks the perspectives of key professionals who operate at the levels of classroom teacher, middle leader (faculty head teacher/principal teacher) and depute head teacher. The study employs a mixed-methods approach using questionnaires, interviews and a focus group discussion within a case study design in order to investigate how teachers experience and understand distributed leadership, its aims and values. The principal results indicate that largely, teachers construe distributed leadership as leadership that is delegated or conferred by senior leaders through the school's systems, teachers understand distributed leadership in terms of the ways in which it has been engendered within the school, teachers experience leadership in a range of ways and teachers believe that distributed leadership has achieved many of its aims. Other results include caveats in terms of teachers' concerns in relation to exercising leadership. Such concerns include: issues of power and authority; teachers' sense of professional/personal identity; teachers' perceptions in relation to their abilities; workload - the influence of the conditions under which teachers have exercised leadership; incentives and perceptions in relation to how additional responsibility for leadership intersects with other duties.This study explores distributed leadership from the perspectives of teachers at different levels within a secondary school, (with the exception of the head teacher). Scottish Government policy is manifest in secondary education in the deployment of distributed leadership practices that seek to maximise output by harnessing the talents of the teaching staff. Aligning with neo-liberalist tendencies, there appears to be an ever-increasing migration of responsibility away from government agencies and into the hands of teachers. This is further evidenced by the prominence within policy of teachers' roles in relation to school improvement and an emphasis upon teachers' agency. The rhetoric used to promote distributed leadership includes notions of increased individual agency, equality, democracy, empowerment, inclusion and collegiality. Despite the above, contemporary theorists contend that distributed leadership remains an ambiguous concept. In order to explore what distributed leadership means to teachers operating within secondary education, this study seeks the perspectives of key professionals who operate at the levels of classroom teacher, middle leader (faculty head teacher/principal teacher) and depute head teacher. The study employs a mixed-methods approach using questionnaires, interviews and a focus group discussion within a case study design in order to investigate how teachers experience and understand distributed leadership, its aims and values. The principal results indicate that largely, teachers construe distributed leadership as leadership that is delegated or conferred by senior leaders through the school's systems, teachers understand distributed leadership in terms of the ways in which it has been engendered within the school, teachers experience leadership in a range of ways and teachers believe that distributed leadership has achieved many of its aims. Other results include caveats in terms of teachers' concerns in relation to exercising leadership. Such concerns include: issues of power and authority; teachers' sense of professional/personal identity; teachers' perceptions in relation to their abilities; workload - the influence of the conditions under which teachers have exercised leadership; incentives and perceptions in relation to how additional responsibility for leadership intersects with other duties
Atypicalities of social functioning in children with Williams syndrome
Get PDFChildren with Williams syndrome (WS) are often reported to show a hyper-social phenotype which can pose implications for their interactions with strangers and peers. The present thesis aimed to obtain an in depth examination of two key areas of social difficulty in children with WS: social approach behaviour (SAB) and peer relationships. A multi-informant approach was used in order to examine the nature and stability of these atypicalities across environmental settings and from different perspectives.Within the present thesis, five studies are reported. Within chapters 3, 4 and 5, SAB was examined in children with WS (aged 7-16 years) by administering an experimental rating task (Adolph's Approachability Task), a parent questionnaire and semi-structured interview. The children with WS indicated significantly higher levels of SAB in Adolph's Approachability Task than typically developing (TD) children matched on verbal ability and TD children matched on non-verbal ability. These high levels of SAB were reported by parents to have substantial implications for the children's vulnerability and family life. However, there was within-syndrome variance in the manifestation of this SAB. Impairment in social functioning, specifically deficits within social cognition and social awareness, were significantly associated with levels of SAB in the children with WS. Within chapters 6 and 7, questionnaires and interviews were used to solicit the perceptions of children with WS, their parents and teachers regarding the child's peer relationships. Parents and teachers reported that many of the children with WS had difficulties forming and sustaining friendships and demonstrated atypical patterns of behaviour during social interactions. However, these peer relationship difficulties were not reported by the children themselves. Peer relationship difficulties were found to be significantly associated with the children's deficits within social communication, social cognition and social awareness.The findings from the current thesis provide insight into substantial social difficulties among many children with WS. Importantly, and in line with the heterogeneous nature of the disorder, there was within-syndrome variance in the children's social functioning. The present findings have important implications for both research and practice. These implications will be discussed, with suggestions for future research.Children with Williams syndrome (WS) are often reported to show a hyper-social phenotype which can pose implications for their interactions with strangers and peers. The present thesis aimed to obtain an in depth examination of two key areas of social difficulty in children with WS: social approach behaviour (SAB) and peer relationships. A multi-informant approach was used in order to examine the nature and stability of these atypicalities across environmental settings and from different perspectives.Within the present thesis, five studies are reported. Within chapters 3, 4 and 5, SAB was examined in children with WS (aged 7-16 years) by administering an experimental rating task (Adolph's Approachability Task), a parent questionnaire and semi-structured interview. The children with WS indicated significantly higher levels of SAB in Adolph's Approachability Task than typically developing (TD) children matched on verbal ability and TD children matched on non-verbal ability. These high levels of SAB were reported by parents to have substantial implications for the children's vulnerability and family life. However, there was within-syndrome variance in the manifestation of this SAB. Impairment in social functioning, specifically deficits within social cognition and social awareness, were significantly associated with levels of SAB in the children with WS. Within chapters 6 and 7, questionnaires and interviews were used to solicit the perceptions of children with WS, their parents and teachers regarding the child's peer relationships. Parents and teachers reported that many of the children with WS had difficulties forming and sustaining friendships and demonstrated atypical patterns of behaviour during social interactions. However, these peer relationship difficulties were not reported by the children themselves. Peer relationship difficulties were found to be significantly associated with the children's deficits within social communication, social cognition and social awareness.The findings from the current thesis provide insight into substantial social difficulties among many children with WS. Importantly, and in line with the heterogeneous nature of the disorder, there was within-syndrome variance in the children's social functioning. The present findings have important implications for both research and practice. These implications will be discussed, with suggestions for future research
The orchestration role of innovation intermediary : a case of corporate accelerator programme
Get PDFThe pace of innovation intermediary research has accelerated in recent years, spurred on by new socio-economic models, digital technologies, the local and global challenges of population growth and environmental pressure. Research on innovation intermediaries is predicated on the idea that intermediaries act as a catalyst for innovation to address these changes and challenges. The development of innovation management practices toward openness and emerging socio-economic models have changed the roles and supporting activities of innovation intermediaries. Open innovation literature suggests that corporate accelerators are one way for corporations to access external sources of innovation as part of the ecosystem. The corporate accelerator is one of the available innovation intermediary types and provides a unique position that could support innovation for both worlds:corporations and start-up firms. But despite its importance, corporate accelerator program and its value creation to the corporate and start-ups remains poorly governed and understood. This research aims to examine the central role of the value model that a corporate accelerator as an innovation intermediary develops to manage and grow an innovation ecosystem and how value capture-related arrangements emerge in the design of corporate accelerator programmes. The emergent model defines the value creation potential for the start-ups and corporate, in this way shows how it is crucial in driving succesful open colloborative innovation inititatives as well as the orchestration role of innovation intermediaries.The mix-method research was applied to answer three interrelated research questions: 1) How does a corporate accelerator perform the orchestration roles of an innovation intermediary? 2) What is the value created for corporations through a corporate accelerator programme? 3) What is the value created for start-ups from participating in corporate accelerator programmes? A case study was the main method used to understand the functions, roles, process, and value creation of corporate accelerator program for corporations. The case study was conducted in an Indonesian corporate accelerator named Indigo Creative Nation (ICN). The program was developed by Telkom Indonesia; an Indonesian state-owned enterprise specialises in the telecommunications industry. Additionally, a survey was conducted to complement the result with information regarding value creation for start-ups.As a result: 1) a model of orchestration role that comprises: the functions, the roles, and the stage of corporate accelerator programme, and 2) a model of value creation of corporate accelerator that includes sources of value for the corporation and start-ups, were developed. This study contributes to the knowledge of innovation intermediary through the advancement of conceptual understanding of the orchestration role of innovation intermediary through corporate accelerator programme. This study also provided empirical insights into innovation intermediary practice that complements the considerable theorising reported in the literature.The pace of innovation intermediary research has accelerated in recent years, spurred on by new socio-economic models, digital technologies, the local and global challenges of population growth and environmental pressure. Research on innovation intermediaries is predicated on the idea that intermediaries act as a catalyst for innovation to address these changes and challenges. The development of innovation management practices toward openness and emerging socio-economic models have changed the roles and supporting activities of innovation intermediaries. Open innovation literature suggests that corporate accelerators are one way for corporations to access external sources of innovation as part of the ecosystem. The corporate accelerator is one of the available innovation intermediary types and provides a unique position that could support innovation for both worlds:corporations and start-up firms. But despite its importance, corporate accelerator program and its value creation to the corporate and start-ups remains poorly governed and understood. This research aims to examine the central role of the value model that a corporate accelerator as an innovation intermediary develops to manage and grow an innovation ecosystem and how value capture-related arrangements emerge in the design of corporate accelerator programmes. The emergent model defines the value creation potential for the start-ups and corporate, in this way shows how it is crucial in driving succesful open colloborative innovation inititatives as well as the orchestration role of innovation intermediaries.The mix-method research was applied to answer three interrelated research questions: 1) How does a corporate accelerator perform the orchestration roles of an innovation intermediary? 2) What is the value created for corporations through a corporate accelerator programme? 3) What is the value created for start-ups from participating in corporate accelerator programmes? A case study was the main method used to understand the functions, roles, process, and value creation of corporate accelerator program for corporations. The case study was conducted in an Indonesian corporate accelerator named Indigo Creative Nation (ICN). The program was developed by Telkom Indonesia; an Indonesian state-owned enterprise specialises in the telecommunications industry. Additionally, a survey was conducted to complement the result with information regarding value creation for start-ups.As a result: 1) a model of orchestration role that comprises: the functions, the roles, and the stage of corporate accelerator programme, and 2) a model of value creation of corporate accelerator that includes sources of value for the corporation and start-ups, were developed. This study contributes to the knowledge of innovation intermediary through the advancement of conceptual understanding of the orchestration role of innovation intermediary through corporate accelerator programme. This study also provided empirical insights into innovation intermediary practice that complements the considerable theorising reported in the literature
Perceptual decision-making : behavioural and chemogenetics approaches in murine auditory-based task
Get PDFPerceptual decision-making, in recent decades, has become one of the central topics in neuroscience. Combining behaviour with techniques for neural activity monitoring and modulation allows to study structures and mechanisms involved in the process. Elucidating its elements and functional connectivity will not only deepen our knowledge of this matter but also provide with information essential to answer more complex questions related to mechanisms guiding our perception of the world. The view on this topic has also been remodelled in recent years switching from seeing the brain as an observer of events to an active analyst.In the past various studies were carried out on the topic of perceptual decision making, basing mainly on visual paradigms in humans and non-human primates.Thanks to developments in technology, genetics and behavioural paradigms, studies in rodents spanning through different sensory modalities are more readily implemented allowing for more in-depth analysis.In this thesis I developed and used auditory-based detection task to study perceptual decision-making on the example of temporal expectations in mice. Further, I combined this paradigm with chemogenetics to examine the results of modulation of activity in auditory cortex on sound detection in behaviour task. Finally, during electrophysiological recordings from auditory cortex, I looked at effects of modulation of neural activity using chemogenetics. These acute experiments were performed in anaesthetized mice.The results have proven that mice model is a highly useful tool in the study of perceptual decision-making, allowing for combination of behavioural task with neural activity monitoring and modulation. In the behavioural task the influence of foreperiod duration on reaction time was not confirmed but a correlation between foreperiod presentation ratio and reaction time was observed.. Implementation of chemogenetics in behavioural paradigm influenced hit rate and reaction time dynamics only for some of the higher sound intensities, therefore not providing confirmation of effect of used technique on behaviour. In electrophysiological recordings, statistically significant changes in levels of neural activity after activation of chemogenetics were reported for both sound- evoked and no-sound related activity in auditory cortex. Altogether, the obtained results do not provide confirmation of presented research theses which presumed the importance of auditory cortex for perceptual decision-making. However, due to the complexity of the matter in question, further studies are needed.Perceptual decision-making, in recent decades, has become one of the central topics in neuroscience. Combining behaviour with techniques for neural activity monitoring and modulation allows to study structures and mechanisms involved in the process. Elucidating its elements and functional connectivity will not only deepen our knowledge of this matter but also provide with information essential to answer more complex questions related to mechanisms guiding our perception of the world. The view on this topic has also been remodelled in recent years switching from seeing the brain as an observer of events to an active analyst.In the past various studies were carried out on the topic of perceptual decision making, basing mainly on visual paradigms in humans and non-human primates.Thanks to developments in technology, genetics and behavioural paradigms, studies in rodents spanning through different sensory modalities are more readily implemented allowing for more in-depth analysis.In this thesis I developed and used auditory-based detection task to study perceptual decision-making on the example of temporal expectations in mice. Further, I combined this paradigm with chemogenetics to examine the results of modulation of activity in auditory cortex on sound detection in behaviour task. Finally, during electrophysiological recordings from auditory cortex, I looked at effects of modulation of neural activity using chemogenetics. These acute experiments were performed in anaesthetized mice.The results have proven that mice model is a highly useful tool in the study of perceptual decision-making, allowing for combination of behavioural task with neural activity monitoring and modulation. In the behavioural task the influence of foreperiod duration on reaction time was not confirmed but a correlation between foreperiod presentation ratio and reaction time was observed.. Implementation of chemogenetics in behavioural paradigm influenced hit rate and reaction time dynamics only for some of the higher sound intensities, therefore not providing confirmation of effect of used technique on behaviour. In electrophysiological recordings, statistically significant changes in levels of neural activity after activation of chemogenetics were reported for both sound- evoked and no-sound related activity in auditory cortex. Altogether, the obtained results do not provide confirmation of presented research theses which presumed the importance of auditory cortex for perceptual decision-making. However, due to the complexity of the matter in question, further studies are needed
Morrissey and the ghost charabanc : (exploring the ghost charabanc)
No full textThe following is a collection of poetry under the title 'Morrissey and the Ghost Charabanc', including a contents page and informal notes on the poems. This is followed by an essay entitled 'Exploring the Ghost Charabanc' which looks at framing and framing devices for the poems, Icons and notions of fame, intertextuality, tangential ekphrasis and methodology, This is followed by a bibliography.The following is a collection of poetry under the title 'Morrissey and the Ghost Charabanc', including a contents page and informal notes on the poems. This is followed by an essay entitled 'Exploring the Ghost Charabanc' which looks at framing and framing devices for the poems, Icons and notions of fame, intertextuality, tangential ekphrasis and methodology, This is followed by a bibliography
Computational studies on molecular recognition in chymosin complexes and related systems
No full textThis thesis focuses on molecular recognition in chymosin complexes using various computational approaches used for studying protein-ligand systems. Three computational investigations are presented in this thesis. The first research project, titled, 'Allosteric-Activation Mechanism Of BovineChymosin', is presented in chapter 5. The study investigates the aspartic protease, bovine chymosin, which catalyses the proteolysis of k-casein proteins in milk. The research presented in this chapter employed two computational techniques, molecular dynamics and bias exchange metadynamics simulations, to study the mechanism of allosteric-activation and to compute the free energy surface for the process. The simulations reveal that allosteric activation is initiated by interactions between the HPHPH sequence of k-casein and a small a-helical region of chymosin (residues 112-116). A small conformational change in the a-helix causes the side chain of Phe114 to vacate a pocket that may then be occupied by the sidechain of Tyr77. The free energy surface for the self-inhibited to open transition is significantly altered by the presence of the HPHPH sequence of k-casein. The second research project, named, 'Effect of Mutations in Bovine or Camel Chymosin on the Thermodynamics of Binding k-Caseins', is presented in chapter 6. Both bovine and camel chymosin catalyse the proteolysis of a milk protein, k-casein, which helps to initiate milk coagulation. The research in this chapter reports computational alanine scanning calculations in four chymosin k-casein complexes, helping to elucidate the influence that individual residues have on the protein-ligand binding thermodynamics. Of the 12 sequence differences in the binding sites of bovine and camel chymosin, eight are shown to be particularly important for understanding differences in the binding thermodynamics (Asp112Glu, Lys221Val, Gln242Arg, Gln278Lys. Glu290Asp, His292Asn,Gln294Glu, and Lys295Leu. Residue in bovine chymosin written first). The final research project of this thesis titled, 'Comparative Molecular Field Analysis using Molecular Integral Equation Theory', is delivered in chapter 7. The study reports, and thoroughly benchmarks, a new method for 3D-QSAR that uses a classical statistical mechanics based solvent model combined with machine learning. Recently, Gussregen et al. used solute-solvent distribution functions calculated by the 3D Reference Interaction Site Model (3D-RISM) in a 3D-QSAR model to predict the binding affinities of serine protease inhibitors. The work carried out for this thesis extends this idea by introducing probe atoms into the 3D-RISM solvent model in order to capture other molecular interactions in addition to those related to hydration/dehydration. The CARMa models have been thoroughly benchmarked against other 3D-QSAR methods across six different datasets, demonstrating that CARMa is an extremely robust method, outperforming other field-based QSAR methods.This thesis focuses on molecular recognition in chymosin complexes using various computational approaches used for studying protein-ligand systems. Three computational investigations are presented in this thesis. The first research project, titled, 'Allosteric-Activation Mechanism Of BovineChymosin', is presented in chapter 5. The study investigates the aspartic protease, bovine chymosin, which catalyses the proteolysis of k-casein proteins in milk. The research presented in this chapter employed two computational techniques, molecular dynamics and bias exchange metadynamics simulations, to study the mechanism of allosteric-activation and to compute the free energy surface for the process. The simulations reveal that allosteric activation is initiated by interactions between the HPHPH sequence of k-casein and a small a-helical region of chymosin (residues 112-116). A small conformational change in the a-helix causes the side chain of Phe114 to vacate a pocket that may then be occupied by the sidechain of Tyr77. The free energy surface for the self-inhibited to open transition is significantly altered by the presence of the HPHPH sequence of k-casein. The second research project, named, 'Effect of Mutations in Bovine or Camel Chymosin on the Thermodynamics of Binding k-Caseins', is presented in chapter 6. Both bovine and camel chymosin catalyse the proteolysis of a milk protein, k-casein, which helps to initiate milk coagulation. The research in this chapter reports computational alanine scanning calculations in four chymosin k-casein complexes, helping to elucidate the influence that individual residues have on the protein-ligand binding thermodynamics. Of the 12 sequence differences in the binding sites of bovine and camel chymosin, eight are shown to be particularly important for understanding differences in the binding thermodynamics (Asp112Glu, Lys221Val, Gln242Arg, Gln278Lys. Glu290Asp, His292Asn,Gln294Glu, and Lys295Leu. Residue in bovine chymosin written first). The final research project of this thesis titled, 'Comparative Molecular Field Analysis using Molecular Integral Equation Theory', is delivered in chapter 7. The study reports, and thoroughly benchmarks, a new method for 3D-QSAR that uses a classical statistical mechanics based solvent model combined with machine learning. Recently, Gussregen et al. used solute-solvent distribution functions calculated by the 3D Reference Interaction Site Model (3D-RISM) in a 3D-QSAR model to predict the binding affinities of serine protease inhibitors. The work carried out for this thesis extends this idea by introducing probe atoms into the 3D-RISM solvent model in order to capture other molecular interactions in addition to those related to hydration/dehydration. The CARMa models have been thoroughly benchmarked against other 3D-QSAR methods across six different datasets, demonstrating that CARMa is an extremely robust method, outperforming other field-based QSAR methods
'Please Miss, I did that before in nursery!' : achieving curriculum continuity and progression in children's learning across the Scottish Curriculum for Excellence - Early Level from nursery settings to Primary 1
Get PDFIn Scotland, the Curriculum for Excellence-Early Level proposes to provide continuity of curriculum experience for children transitioning from nursery to primary school. Over the last three decades, national and international studies have identified the key factors, which contribute to an effective transition. These studies also highlight some of the emotional, social, and cognitive implications for children starting school.This study aimed, through case study methods, to explore whether there are barriers and challenges facing practitioners and teachers in achieving curriculum continuity and progression in children's learning across the 'early level'. The study, informed by a bioecological and sociocultural framework, involved thirteen children, their parents and the staff who worked with them in two nursery settings and three primary schools. Findings demonstrate the importance of the environment, proximal processes and reciprocal relationships between people and contexts over time in achieving curriculum continuity across the 'early level'. Furthermore, the study identified the need for collaborative 'early level' curriculum planning systems and playful pedagogies which empower children to exercise agency, and which recognise and build on children's funds of knowledge. Qualitative data was gathered through participant observations and interviews with adults. Data, analysed using a thematic analysis framework, show that children experienced two 'early level traditions'. Firstly, they experienced the 'nursery' early level tradition and secondly, on moving to school, they experienced the 'Primary 1' early level tradition. Conceptually, as children left the nursery tradition behind and entered the Primary 1 tradition, they stepped into and out of 'contested' and 'unified' spaces, which are proposed to exist in the mesosystem between the two early level traditions. Consistent with a bioecological and sociocultural frame, children's agency and social capital determine the impact of the contested and unified spaces on their adjustment to being learners in the Primary 1 tradition.This study argues that, as a result of variations in pedagogical practices in each tradition, there are possibilities for greater collaboration between practitioners and teachers. Further, the importance of building a play-based, child-initiated pedagogy is foregrounded, if children starting school in Scotland, are to benefit from a flexible, socially constructed, continuous 'early level' curriculum experience.In Scotland, the Curriculum for Excellence-Early Level proposes to provide continuity of curriculum experience for children transitioning from nursery to primary school. Over the last three decades, national and international studies have identified the key factors, which contribute to an effective transition. These studies also highlight some of the emotional, social, and cognitive implications for children starting school.This study aimed, through case study methods, to explore whether there are barriers and challenges facing practitioners and teachers in achieving curriculum continuity and progression in children's learning across the 'early level'. The study, informed by a bioecological and sociocultural framework, involved thirteen children, their parents and the staff who worked with them in two nursery settings and three primary schools. Findings demonstrate the importance of the environment, proximal processes and reciprocal relationships between people and contexts over time in achieving curriculum continuity across the 'early level'. Furthermore, the study identified the need for collaborative 'early level' curriculum planning systems and playful pedagogies which empower children to exercise agency, and which recognise and build on children's funds of knowledge. Qualitative data was gathered through participant observations and interviews with adults. Data, analysed using a thematic analysis framework, show that children experienced two 'early level traditions'. Firstly, they experienced the 'nursery' early level tradition and secondly, on moving to school, they experienced the 'Primary 1' early level tradition. Conceptually, as children left the nursery tradition behind and entered the Primary 1 tradition, they stepped into and out of 'contested' and 'unified' spaces, which are proposed to exist in the mesosystem between the two early level traditions. Consistent with a bioecological and sociocultural frame, children's agency and social capital determine the impact of the contested and unified spaces on their adjustment to being learners in the Primary 1 tradition.This study argues that, as a result of variations in pedagogical practices in each tradition, there are possibilities for greater collaboration between practitioners and teachers. Further, the importance of building a play-based, child-initiated pedagogy is foregrounded, if children starting school in Scotland, are to benefit from a flexible, socially constructed, continuous 'early level' curriculum experience
Understanding the motivators and barriers for adolescents using digital diabetes technology to manage glycaemia in type 1 diabetes
Get PDFType 1 diabetes, a life threatening autoimmune medical condition, affects over 370,000 people in the UK at present. It costs the NHS budget over £1bn annually. Of this population, the adolescent age group are at increased risk of morbidity and mortality issues. The focus of support from parents/caregivers is to achieve stable glycaemia. This support also involves daily interaction with technology to monitor glucose and prevent serious side effects of insulin replacement treatment.;This thesis qualitatively explored the lived experience of adolescents who live with type 1 diabetes, and the impact it can have on their families. Data was collected from interviews (n=7), an online survey (n=26) and a live opinion poll (n=19). The benefits and barriers of current diabetes technology for managing glycaemia in type 1 diabetes, were discussed. Four global themes were identified a priori based on the literature and a total of 34 emerging themes were revealed which contribute to a deeper understanding of the complexities of the use and acceptance of technology for managing glycaemia.;Throughout this research study, it frequently emerged that participant's experiences of technology were related to improvement of glycaemia, in addition to greater control over lifestyle and dietary choices. However, many barriers were also uncovered as participants spoke of the effects of inaccuracy of the current technology, which often led to severe episodes of hypoglycaemia/hyperglycaemia and diabetic ketoacidosis.;Furthermore, visibility of wearing diabetes related devices, often left the adolescent feeling self-conscious and embarrassed. The adhesion of some current devices caused severe skin reaction, leading to reduced usage. Adolescents living with type 1 diabetes, and their families highlighted the need for technology to be predictive with warnings and alerts to prevent hypoglycaemia/hyperglycaemia.;In conclusion, this research study unveiled the complexities of living with type 1 diabetes for the adolescent, which they and their families experience. These complexities are strongly associated with widespread barriers found when using current diabetes technologies. Moreover, these barriers can lead to a withdrawal from use. Improvements in accuracy and application, and reduced visibility of technologies for managing glycaemia are needed to maximise user engagement and benefit.Type 1 diabetes, a life threatening autoimmune medical condition, affects over 370,000 people in the UK at present. It costs the NHS budget over £1bn annually. Of this population, the adolescent age group are at increased risk of morbidity and mortality issues. The focus of support from parents/caregivers is to achieve stable glycaemia. This support also involves daily interaction with technology to monitor glucose and prevent serious side effects of insulin replacement treatment.;This thesis qualitatively explored the lived experience of adolescents who live with type 1 diabetes, and the impact it can have on their families. Data was collected from interviews (n=7), an online survey (n=26) and a live opinion poll (n=19). The benefits and barriers of current diabetes technology for managing glycaemia in type 1 diabetes, were discussed. Four global themes were identified a priori based on the literature and a total of 34 emerging themes were revealed which contribute to a deeper understanding of the complexities of the use and acceptance of technology for managing glycaemia.;Throughout this research study, it frequently emerged that participant's experiences of technology were related to improvement of glycaemia, in addition to greater control over lifestyle and dietary choices. However, many barriers were also uncovered as participants spoke of the effects of inaccuracy of the current technology, which often led to severe episodes of hypoglycaemia/hyperglycaemia and diabetic ketoacidosis.;Furthermore, visibility of wearing diabetes related devices, often left the adolescent feeling self-conscious and embarrassed. The adhesion of some current devices caused severe skin reaction, leading to reduced usage. Adolescents living with type 1 diabetes, and their families highlighted the need for technology to be predictive with warnings and alerts to prevent hypoglycaemia/hyperglycaemia.;In conclusion, this research study unveiled the complexities of living with type 1 diabetes for the adolescent, which they and their families experience. These complexities are strongly associated with widespread barriers found when using current diabetes technologies. Moreover, these barriers can lead to a withdrawal from use. Improvements in accuracy and application, and reduced visibility of technologies for managing glycaemia are needed to maximise user engagement and benefit
Development of a model for integrating resilience engineering principles to ship management system [sic] to enhance navigational bridge operation
Get PDFAnalysis of the MAIB (Marine Accident Investigation Branch) accidents reports show that out of 127 recorded incidents between 2010 and 2015, 56 ship accidents were caused by operational failures on the navigation bridge. Setbacks on a ship's bridge led to three types of accidents: collision, grounding and contact. The analyses classified the reasons of the bridge deficiencies to task failures (causes of accidents), Sub-factors, mitigation deficiencies and accident impacts. This fact illustrates the need to improve safety standards with the bridge operation. This research work aims to address a new approach to barrier management concerning the operation of the navigation bridge system in a framework that incorporates the principles of resilience engineering to enhance shipping safety. The work process contains navigation bridge description, the definition of the safety performance, including fundamental resilience, developing application methods and a design scheme for control and maintenance. The approach introduces resilience-engineering elements: anticipation, monitoring, learning, and responding. The bow-tie model supports the approach by visualising the barrier system in a constructive perspective. The downside of this approach is the large amount of data received during the process, forcing the implementer to select the relevant information and to be specific when choosing the application area. Also, not all accidents have linear steps for the event, potentially forcing the implementer to be selective and bring the function elements and resilience resources effectively in line to be manageable and applicable. All these obstacles can be overcome by continuous application of the method. The benefits of this approach are minimising the errors of the bridge operator by improving the anticipation, enhancing the operation performance via the learning technique, improving the monitoring system and the efficiency of the safety planning, increasing the system reliability by maintaining a strong and flexible system able to response during changing conditions.Analysis of the MAIB (Marine Accident Investigation Branch) accidents reports show that out of 127 recorded incidents between 2010 and 2015, 56 ship accidents were caused by operational failures on the navigation bridge. Setbacks on a ship's bridge led to three types of accidents: collision, grounding and contact. The analyses classified the reasons of the bridge deficiencies to task failures (causes of accidents), Sub-factors, mitigation deficiencies and accident impacts. This fact illustrates the need to improve safety standards with the bridge operation. This research work aims to address a new approach to barrier management concerning the operation of the navigation bridge system in a framework that incorporates the principles of resilience engineering to enhance shipping safety. The work process contains navigation bridge description, the definition of the safety performance, including fundamental resilience, developing application methods and a design scheme for control and maintenance. The approach introduces resilience-engineering elements: anticipation, monitoring, learning, and responding. The bow-tie model supports the approach by visualising the barrier system in a constructive perspective. The downside of this approach is the large amount of data received during the process, forcing the implementer to select the relevant information and to be specific when choosing the application area. Also, not all accidents have linear steps for the event, potentially forcing the implementer to be selective and bring the function elements and resilience resources effectively in line to be manageable and applicable. All these obstacles can be overcome by continuous application of the method. The benefits of this approach are minimising the errors of the bridge operator by improving the anticipation, enhancing the operation performance via the learning technique, improving the monitoring system and the efficiency of the safety planning, increasing the system reliability by maintaining a strong and flexible system able to response during changing conditions
Regulation of human CXCL12 expression by IKKα in bone cancer and cancer associated fibroblasts derived from clinical specimens obtained from breast cancer patients
Get PDFThis thesis was previously held under moratorium from 12/02/19 to 21/05/2021.Despite great progress in surgery, radio- and chemotherapy, the prognosis and treatment options for osteosarcoma and breast cancer remain extremely poor with a high inclination for metastatic spread to other organs. Compelling evidence has demonstrated that CXCL12/CXCR4 is implicated in human tumour pathogenesis. Therefore, targeting CXCL12 expression is a logical strategy for treating cancer patients.;Moreover, studies have implicated inhibitory Kappa B kinase alpha (IKKα) as a key regulator in the non-canonical NF-κB pathway and it has recently been demonstrated that IKKα can regulate CXCL12 expression. Therefore, the aim of the current study was to investigate the role of the IKKα-mediated non-canonical NF-κB pathway in the regulation of CXCL12 expression in a human bone osteosarcoma cell line (U2OS) and cancer-associated fibroblasts (CAFs) derived from clinical specimens obtained from human breast cancer patients to determine the validity of this approach.;Initially, newly synthesised selective IKKα inhibitors (SU compounds) were characterised in LTα1β2-stimulated U2OS cells and were shown to be moderately potent and selective for the non-canonical NF-κB pathway, whereas they exerted little effect on the classical NF-κB pathway at high micromolar concentrations. In addition, it was unexpectedly found that both TNFα and IL-1β were strong and early activators of the non-canonical NF-κB pathway activated by IKKα, which was established using both siRNA and the selective inhibitors.;Both TNFα and IL-1β but not LTα1β2, stimulated a strong increase in CXCL12 in reporter U2OS cells and when endogenously measured using RT-qPCR. CXCL12 expression was susceptible to both siRNA knock down and IKKα inhibitors, suggesting that the early strong IKKα signal was significant for expression.;We further examined the role of IKKα in CXCL12 expression in CAFs derived from breast cancer patients. ELISA data revealed that CXCL12 protein secretion in CAFs was significantly higher than that of normal fibroblasts (NFs). However, our findings did not demonstrate a significant difference in the activation of the non-canonical NF-κB pathway by LTα1β2. Moreover, the studies conducted using siRNA IKKα and SU compounds showed that CXCL12 expression was not altered in CAFs or NFs. Overall, these findings indicate that IKKα is not required for the regulation of CXCL12 expression in CAFs.;Taken together, these results highlight a novel early kinetically distinct mode of non-canonical NF-κB signalling by IKKα, which is significant in the induction of CXCL12 in bone cells. Therefore, selective IKKα inhibition may be a target for cancer therapy but only for certain types of cancer and is not always linked to CXCL12 inhibition.Despite great progress in surgery, radio- and chemotherapy, the prognosis and treatment options for osteosarcoma and breast cancer remain extremely poor with a high inclination for metastatic spread to other organs. Compelling evidence has demonstrated that CXCL12/CXCR4 is implicated in human tumour pathogenesis. Therefore, targeting CXCL12 expression is a logical strategy for treating cancer patients.;Moreover, studies have implicated inhibitory Kappa B kinase alpha (IKKα) as a key regulator in the non-canonical NF-κB pathway and it has recently been demonstrated that IKKα can regulate CXCL12 expression. Therefore, the aim of the current study was to investigate the role of the IKKα-mediated non-canonical NF-κB pathway in the regulation of CXCL12 expression in a human bone osteosarcoma cell line (U2OS) and cancer-associated fibroblasts (CAFs) derived from clinical specimens obtained from human breast cancer patients to determine the validity of this approach.;Initially, newly synthesised selective IKKα inhibitors (SU compounds) were characterised in LTα1β2-stimulated U2OS cells and were shown to be moderately potent and selective for the non-canonical NF-κB pathway, whereas they exerted little effect on the classical NF-κB pathway at high micromolar concentrations. In addition, it was unexpectedly found that both TNFα and IL-1β were strong and early activators of the non-canonical NF-κB pathway activated by IKKα, which was established using both siRNA and the selective inhibitors.;Both TNFα and IL-1β but not LTα1β2, stimulated a strong increase in CXCL12 in reporter U2OS cells and when endogenously measured using RT-qPCR. CXCL12 expression was susceptible to both siRNA knock down and IKKα inhibitors, suggesting that the early strong IKKα signal was significant for expression.;We further examined the role of IKKα in CXCL12 expression in CAFs derived from breast cancer patients. ELISA data revealed that CXCL12 protein secretion in CAFs was significantly higher than that of normal fibroblasts (NFs). However, our findings did not demonstrate a significant difference in the activation of the non-canonical NF-κB pathway by LTα1β2. Moreover, the studies conducted using siRNA IKKα and SU compounds showed that CXCL12 expression was not altered in CAFs or NFs. Overall, these findings indicate that IKKα is not required for the regulation of CXCL12 expression in CAFs.;Taken together, these results highlight a novel early kinetically distinct mode of non-canonical NF-κB signalling by IKKα, which is significant in the induction of CXCL12 in bone cells. Therefore, selective IKKα inhibition may be a target for cancer therapy but only for certain types of cancer and is not always linked to CXCL12 inhibition
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