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Carbapenem and piperacillin-tazobactam prescribing in a hospital setting in Kingdom of Saudi Arabia : a mixed methodology study
Get PDFBackground: Antimicrobial resistance (AMR) is spreading rapidly and is considered tobe one of the greatest public threats worldwide. The inappropriate use of broadspectrum antimicrobials has contributed to the emergence of AMR. The WHO hasdeveloped Access, Watch, Reserve (AWaRe) classification to support hospitals andcountries in promoting the appropriate utilisation of antimicrobials. Studying broadspectrum antimicrobial utilisation and the determinants of broad-spectrumantimicrobial prescribing can assist in developing strategies and policies to improvethe local prescribing practice for these agents.Aim: To evaluate the practices of broad-spectrum antimicrobial prescribing toprovide potentially effective and feasible recommendations and interventions thatwill result in improvements in broad-spectrum antimicrobial prescribing practices ina hospital setting in the Kingdom of Saudi Arabia (KSA).Methods: An explanatory sequential mixed methods approach was adopted. First, aquantitative, observational, retrospective, cross-sectional, drug utilisation study,which included adult patient data on carbapenems (imipenem/cilastatin ormeropenem) and piperacillin/tazobactam use retrieved from a hospital database forthe period from 1 January 2016 to 31 December 2017, was conducted followed by aqualitative study of physicians' views and perceptions of broad-spectrumantimicrobial prescribing. The qualitative study employed semi-structured interviewswith 16 physicians to identify and explore the determinants of broad-spectrumantimicrobial prescribing practices, recommendations to improve practice andpossible barriers. This study was carried out in a single tertiary care institution in theKSA.Results: A total of 2,871 patients received 5,250 courses of antimicrobial treatmentwith at least one of the studied broad-spectrum antimicrobials across 3,671 patientadmissions over a two-year period. It was shown that 4,106 (82%) of broadspectrum antimicrobials were prescribed for empiric indications. Of the assessedprescriptions, only 2,787 (56.5%) were prescribed appropriately, with 2,142 (43.5%)deemed inappropriate. The three most common reasons for inappropriate empiricperceptions were: spectrum of activity was too broad 1029 (40%), antimicrobial usedwithout a culture request 929 (36.2%), and failure of suitable antimicrobial deescalation 570 (22.2%). Interview findings identified key determinants of broadspectrum antimicrobial prescribing practices, including patient co-morbidities andclinical presentations, the unavailability of local guidelines, physicians’ perceptionsand attitudes toward broad-spectrum antimicrobials prescribing and severalinstitutional constraints. Suggestions prioritised by physicians for improvements tothe practice of prescribing broad-spectrum antimicrobials included education andtraining, monitoring and feedback, improved logistics of care and antimicrobialstewardship.Conclusion: This research adds to our knowledge on broad-spectrum antimicrobialprescribing practices and recommended intervention and strategies for improvingthe appropriateness of broad-spectrum antimicrobials prescribing in a hospitalsetting in the KSA. Implementing a multifaceted intervention can possibly improveantimicrobials prescribing practices. Educating physicians about the importance ofantimicrobial stewardship practices could be considered. Moreover, introducingantimicrobial prescribing guidelines should be significant part of the intervention toimprove the appropriate prescribing of broad-spectrum antimicrobials. Botheducation and guidelines should consider the factors that influence physiciansprescribing and involve physicians to impact effectively and positively on theirinappropriate prescribing practices and reduce the risk of AMR.Background: Antimicrobial resistance (AMR) is spreading rapidly and is considered tobe one of the greatest public threats worldwide. The inappropriate use of broadspectrum antimicrobials has contributed to the emergence of AMR. The WHO hasdeveloped Access, Watch, Reserve (AWaRe) classification to support hospitals andcountries in promoting the appropriate utilisation of antimicrobials. Studying broadspectrum antimicrobial utilisation and the determinants of broad-spectrumantimicrobial prescribing can assist in developing strategies and policies to improvethe local prescribing practice for these agents.Aim: To evaluate the practices of broad-spectrum antimicrobial prescribing toprovide potentially effective and feasible recommendations and interventions thatwill result in improvements in broad-spectrum antimicrobial prescribing practices ina hospital setting in the Kingdom of Saudi Arabia (KSA).Methods: An explanatory sequential mixed methods approach was adopted. First, aquantitative, observational, retrospective, cross-sectional, drug utilisation study,which included adult patient data on carbapenems (imipenem/cilastatin ormeropenem) and piperacillin/tazobactam use retrieved from a hospital database forthe period from 1 January 2016 to 31 December 2017, was conducted followed by aqualitative study of physicians' views and perceptions of broad-spectrumantimicrobial prescribing. The qualitative study employed semi-structured interviewswith 16 physicians to identify and explore the determinants of broad-spectrumantimicrobial prescribing practices, recommendations to improve practice andpossible barriers. This study was carried out in a single tertiary care institution in theKSA.Results: A total of 2,871 patients received 5,250 courses of antimicrobial treatmentwith at least one of the studied broad-spectrum antimicrobials across 3,671 patientadmissions over a two-year period. It was shown that 4,106 (82%) of broadspectrum antimicrobials were prescribed for empiric indications. Of the assessedprescriptions, only 2,787 (56.5%) were prescribed appropriately, with 2,142 (43.5%)deemed inappropriate. The three most common reasons for inappropriate empiricperceptions were: spectrum of activity was too broad 1029 (40%), antimicrobial usedwithout a culture request 929 (36.2%), and failure of suitable antimicrobial deescalation 570 (22.2%). Interview findings identified key determinants of broadspectrum antimicrobial prescribing practices, including patient co-morbidities andclinical presentations, the unavailability of local guidelines, physicians’ perceptionsand attitudes toward broad-spectrum antimicrobials prescribing and severalinstitutional constraints. Suggestions prioritised by physicians for improvements tothe practice of prescribing broad-spectrum antimicrobials included education andtraining, monitoring and feedback, improved logistics of care and antimicrobialstewardship.Conclusion: This research adds to our knowledge on broad-spectrum antimicrobialprescribing practices and recommended intervention and strategies for improvingthe appropriateness of broad-spectrum antimicrobials prescribing in a hospitalsetting in the KSA. Implementing a multifaceted intervention can possibly improveantimicrobials prescribing practices. Educating physicians about the importance ofantimicrobial stewardship practices could be considered. Moreover, introducingantimicrobial prescribing guidelines should be significant part of the intervention toimprove the appropriate prescribing of broad-spectrum antimicrobials. Botheducation and guidelines should consider the factors that influence physiciansprescribing and involve physicians to impact effectively and positively on theirinappropriate prescribing practices and reduce the risk of AMR
Enacting entrepreneurial leadership : a qualitative study of leadership behaviour in the context of Scottish growth-oriented businesses
Get PDFStrategic approaches to venture development highlight the importance of entrepreneurial leadership to business success; yet, there are significant knowledge gaps concerning what entrepreneurial leaders actually do and why they choose such behavioural paths. Situated in pragmatism, this study addresses these gaps by investigating leaders' and followers' perspectives of leadership behaviour associated with opportunity in the context of Scottish Enterprise Account Managed companies. Six case studies produce rich qualitative insight, each with multiple informants reflecting on opportunity-related critical incidents. Beyond cross-sectional investigation, contextual depth is achieved by taking a chronological lens to the temporal dimensions of behaviours characterising entrepreneurial leadership. The approach produces novel insights signalling a spectrum of interlocked behaviours reflecting actioned individual-level attributes and enactments targeting followers' influence and enablement of entrepreneurialism. The analysis also shows the evolving nature of entrepreneurial leadership enactment to correspond to the changing needs of organisations throughout their lifecycle. The case studies suggest that entrepreneurial leaders transition from influencing to enabling behaviours as business moves from pre-organisational to organisational states of development. Finally, qualitative findings reinforce the claims around entrepreneurial leadership's contribution to business success. Overall, the work contributes to the conceptual elucidation of entrepreneurial leadership as a leadership style while furthering understanding of leaders' socially situated and dynamic behaviours striving to instil opportunity-led work behavioursStrategic approaches to venture development highlight the importance of entrepreneurial leadership to business success; yet, there are significant knowledge gaps concerning what entrepreneurial leaders actually do and why they choose such behavioural paths. Situated in pragmatism, this study addresses these gaps by investigating leaders' and followers' perspectives of leadership behaviour associated with opportunity in the context of Scottish Enterprise Account Managed companies. Six case studies produce rich qualitative insight, each with multiple informants reflecting on opportunity-related critical incidents. Beyond cross-sectional investigation, contextual depth is achieved by taking a chronological lens to the temporal dimensions of behaviours characterising entrepreneurial leadership. The approach produces novel insights signalling a spectrum of interlocked behaviours reflecting actioned individual-level attributes and enactments targeting followers' influence and enablement of entrepreneurialism. The analysis also shows the evolving nature of entrepreneurial leadership enactment to correspond to the changing needs of organisations throughout their lifecycle. The case studies suggest that entrepreneurial leaders transition from influencing to enabling behaviours as business moves from pre-organisational to organisational states of development. Finally, qualitative findings reinforce the claims around entrepreneurial leadership's contribution to business success. Overall, the work contributes to the conceptual elucidation of entrepreneurial leadership as a leadership style while furthering understanding of leaders' socially situated and dynamic behaviours striving to instil opportunity-led work behaviour
Honey bee colony losses and analysis of data from a survey of beekeepers in Saudi Arabia
No full textEnhancing navigational safety through increasing situational awareness and teamwork in the bridge
Get PDFIt is well reported in the literature that more than 80% of shipping accidents are attributed to human and organisational factors. Marine accidents are the result of error chains rather than single events. Prevention of accidents has gained the deserved attention by the end of the last century, as the maritime community has realised that despite all the increased safety standards and technological developments, accidents are still occurring, and the system is not resilient to errors at various levels. Furthermore, it has been often ignored that the human element of the maritime system has not been evolving the in the same way that technology is developing; and with the physical capabilities and the limitations of the human is being overlooked. It is considering that 60% of the accident are classed as grounding and collisions, which need to improve navigational safety.;This research aims to minimise the human and organisational factors in the bridge by enhancing the bridge team interaction and increasing the situational awareness of the bridge team in total. This will increase the bridge team performance to communicate and optimise teamwork between bridge team member to avoid accidents. Moreover, this thesis looks into Bridge Resource Management (BRM) elements and its deficiency and develop a new course that is flexible for all bridge team members to increase their efficiency and improve the team's decision-making based on the interpretation of the situation. The novelty of this research is to develop a BRM course to cover all bridge team members to enhance the bridge team performance to be similar to the aviation industry, which requires all aviation pilot and cabin crew to participant in Crew Resource Management (CRM) to be eligible for working in the aeroplanes.;The validation of the new course's effectiveness has been utilised in the full-mission ship's bridge navigational simulator compared to the regular course. Educational scenarios based on real accidents has been established for the validation experiment to evaluate the bridge team participants' performance and actions to avoid the collision.It is well reported in the literature that more than 80% of shipping accidents are attributed to human and organisational factors. Marine accidents are the result of error chains rather than single events. Prevention of accidents has gained the deserved attention by the end of the last century, as the maritime community has realised that despite all the increased safety standards and technological developments, accidents are still occurring, and the system is not resilient to errors at various levels. Furthermore, it has been often ignored that the human element of the maritime system has not been evolving the in the same way that technology is developing; and with the physical capabilities and the limitations of the human is being overlooked. It is considering that 60% of the accident are classed as grounding and collisions, which need to improve navigational safety.;This research aims to minimise the human and organisational factors in the bridge by enhancing the bridge team interaction and increasing the situational awareness of the bridge team in total. This will increase the bridge team performance to communicate and optimise teamwork between bridge team member to avoid accidents. Moreover, this thesis looks into Bridge Resource Management (BRM) elements and its deficiency and develop a new course that is flexible for all bridge team members to increase their efficiency and improve the team's decision-making based on the interpretation of the situation. The novelty of this research is to develop a BRM course to cover all bridge team members to enhance the bridge team performance to be similar to the aviation industry, which requires all aviation pilot and cabin crew to participant in Crew Resource Management (CRM) to be eligible for working in the aeroplanes.;The validation of the new course's effectiveness has been utilised in the full-mission ship's bridge navigational simulator compared to the regular course. Educational scenarios based on real accidents has been established for the validation experiment to evaluate the bridge team participants' performance and actions to avoid the collision
A study of aquatic biomimetic problems using a multi-body dynamics method
Get PDFTo adapt themselves to the aquatic environment, fish have developed extraordinary propulsion and manoeuvring abilities. The physical and biological mechanisms observed in swimming fish can be applied to improve designs of Autonomous Underwater Vehicles (AUV), which can be used for the exploration of undersea resources. Fish swimming is a typical fluid-structure interaction problem, which involves several complicated mechanisms including vortex generation, the coupling of hydrodynamics and body-dynamics, as well as the interplay of fish body locomotion and the kinematics of multiple fins with flexural properties. Although relevant research has been carried out for several decades, there are still lots of phenomena behind aquatic swimming which are worth investigation. This work aims to improve the understanding of the underlying physics and sophisticated interactions in fish swimming. For this purpose, a coupled fluid-structure analysis tool is developed in the current thesis for solving aquatic biomimetic problems.;The developed numerical tool takes advantage of the commercial CFD software ANSYS Fluent to solve the fluid field surrounding swimming fish with high fidelity and utilises the theory of Multi-Body Dynamics (MBD) to simulate the complex locomotion of various types of fish swimming, such as the undulating motion of fish body, self-propelled motion of fish with flexible fins. The MBD theory is implemented in ANSYS Fluent as User Defined Function (UDF). The coupling of these two solvers is achieved by compiling and exchanging force and motion data between the UDF and ANSYS Fluent at each time step. Additionally, to tackle the complex mesh movement in fish swimming simulations, a dynamic mesh function is employed to regenerate and smooth deformed computational mesh.;A series of test cases is firstly studied to validate the various features of the tool, including three actuated connection cases (a discrete undulating fish, the undulating motion of a continuous Anguilliform fish, and the cupping motion of a fish peduncle- Abstract III caudal model) and one passive connection case (a flapping wing with two foils). Results obtained from all these cases meet well with previously published data, which successfully validate the coupled tool developed in this work.;Subsequently, the study of a pufferfish model driven by its multiple fins is carried out to investigate the effects of rigid and flexible fins. Dorsal, anal and caudal fins are included in the model. The morphology and kinematics of the flexible fins are obtained from a live fish experiment. The deformation of the caudal peduncle and the spanwise deformation of fins are ignored. Hydrodynamic performance of the fish with rigid and flexible fins are investigated, focusing on their differences in induced velocity, hydrodynamic force, surface pressure, vortex structure, power and efficiency.;The role of dorsal and anal fins during unsteady swimming is lastly analysed. Comparisons are made by simulating the pufferfish model with and without the dorsal and anal fins. A perturbation is given in the flow as a constant incoming velocity to study the performance of the models under unsteady flow conditions. The results are analysed from the following aspects: displacement, velocity, hydrodynamic force, power and efficiency. Interactions between the fish and fluid flow are analysed by visualising the vortices generated by the fish body as well as its multiple fins.To adapt themselves to the aquatic environment, fish have developed extraordinary propulsion and manoeuvring abilities. The physical and biological mechanisms observed in swimming fish can be applied to improve designs of Autonomous Underwater Vehicles (AUV), which can be used for the exploration of undersea resources. Fish swimming is a typical fluid-structure interaction problem, which involves several complicated mechanisms including vortex generation, the coupling of hydrodynamics and body-dynamics, as well as the interplay of fish body locomotion and the kinematics of multiple fins with flexural properties. Although relevant research has been carried out for several decades, there are still lots of phenomena behind aquatic swimming which are worth investigation. This work aims to improve the understanding of the underlying physics and sophisticated interactions in fish swimming. For this purpose, a coupled fluid-structure analysis tool is developed in the current thesis for solving aquatic biomimetic problems.;The developed numerical tool takes advantage of the commercial CFD software ANSYS Fluent to solve the fluid field surrounding swimming fish with high fidelity and utilises the theory of Multi-Body Dynamics (MBD) to simulate the complex locomotion of various types of fish swimming, such as the undulating motion of fish body, self-propelled motion of fish with flexible fins. The MBD theory is implemented in ANSYS Fluent as User Defined Function (UDF). The coupling of these two solvers is achieved by compiling and exchanging force and motion data between the UDF and ANSYS Fluent at each time step. Additionally, to tackle the complex mesh movement in fish swimming simulations, a dynamic mesh function is employed to regenerate and smooth deformed computational mesh.;A series of test cases is firstly studied to validate the various features of the tool, including three actuated connection cases (a discrete undulating fish, the undulating motion of a continuous Anguilliform fish, and the cupping motion of a fish peduncle- Abstract III caudal model) and one passive connection case (a flapping wing with two foils). Results obtained from all these cases meet well with previously published data, which successfully validate the coupled tool developed in this work.;Subsequently, the study of a pufferfish model driven by its multiple fins is carried out to investigate the effects of rigid and flexible fins. Dorsal, anal and caudal fins are included in the model. The morphology and kinematics of the flexible fins are obtained from a live fish experiment. The deformation of the caudal peduncle and the spanwise deformation of fins are ignored. Hydrodynamic performance of the fish with rigid and flexible fins are investigated, focusing on their differences in induced velocity, hydrodynamic force, surface pressure, vortex structure, power and efficiency.;The role of dorsal and anal fins during unsteady swimming is lastly analysed. Comparisons are made by simulating the pufferfish model with and without the dorsal and anal fins. A perturbation is given in the flow as a constant incoming velocity to study the performance of the models under unsteady flow conditions. The results are analysed from the following aspects: displacement, velocity, hydrodynamic force, power and efficiency. Interactions between the fish and fluid flow are analysed by visualising the vortices generated by the fish body as well as its multiple fins
An axiomatic universe for industry 4
Get PDFSince its emergence in 2011, Industry 4.0 aims to maximise productivity and efficiency in manufacturing and has gained momentum, both in academy as well as in industry. Many frameworks and international initiatives have been proposed for the implementation of Industry 4. However, research shows that industry is facing difficulties with implementing this concept and a formal definition of Industry 4 has not yet been agreed upon. To address these issues, this Thesis proposes a formal logic framework for the implementation of Industry 4 as formal logic enables rigours construction and explanation of a concept. Moreover, formal logic allows for automation of the framework.;The framework is based on a thorough literature review and its analysis where the key characteristics of Industry 4 are identified. The framework uses an axiomatic approach to formalise Industry 4. An expert system for practical applications of the framework is presented. The expert system enables an automatic inference of the rules and is used for part of the evaluation of the framework. The soundness, completeness, utility and applicability of the framework are evaluated by an academic expert and through two case studies. The outcome of the evaluation was used to refine the framework.;The evaluation revealed that the framework features the key characteristics of Industry 4 in a manufacturing setting and can successfully be applied to manufacturing organisations as well as devices. The findings of the evaluation support the research question, that is whether Industry 4 can be described with formal logic to identify the key components that should be considered before Industry 4 is implemented. The framework for this Thesis will guide industry with the implementation of Industry 4. Future work includes, for example, incorporating more elements of Industry 4 that were not within the scope of the Thesis and further developing the application software.Since its emergence in 2011, Industry 4.0 aims to maximise productivity and efficiency in manufacturing and has gained momentum, both in academy as well as in industry. Many frameworks and international initiatives have been proposed for the implementation of Industry 4. However, research shows that industry is facing difficulties with implementing this concept and a formal definition of Industry 4 has not yet been agreed upon. To address these issues, this Thesis proposes a formal logic framework for the implementation of Industry 4 as formal logic enables rigours construction and explanation of a concept. Moreover, formal logic allows for automation of the framework.;The framework is based on a thorough literature review and its analysis where the key characteristics of Industry 4 are identified. The framework uses an axiomatic approach to formalise Industry 4. An expert system for practical applications of the framework is presented. The expert system enables an automatic inference of the rules and is used for part of the evaluation of the framework. The soundness, completeness, utility and applicability of the framework are evaluated by an academic expert and through two case studies. The outcome of the evaluation was used to refine the framework.;The evaluation revealed that the framework features the key characteristics of Industry 4 in a manufacturing setting and can successfully be applied to manufacturing organisations as well as devices. The findings of the evaluation support the research question, that is whether Industry 4 can be described with formal logic to identify the key components that should be considered before Industry 4 is implemented. The framework for this Thesis will guide industry with the implementation of Industry 4. Future work includes, for example, incorporating more elements of Industry 4 that were not within the scope of the Thesis and further developing the application software
Investigating the mechanisms and outcomes of Sprouty-2 S-acylation
Get PDFS-acylation is a reversible post-translational modification (PTM) that regulates proteins in several ways, including by modulating trafficking, stability and protein interactions. This PTM is mediated by twenty-three zinc finger DHHC (zDHHC) enzymes that display distinct activity and substrate selectivity profiles. Sprouty (SPRY) proteins are regulators of Receptor Tyrosine Kinase (RTK) signalling and play a major role in maintaining cellular homeostasis. Indeed, their deregulation is linked to tumorigenesis, developmental defects and neurological diseases.;The defining feature of SPRY proteins is a large cysteine-rich domain (CRD), which is modified by S-acylation. In this thesis, cell-based and cell-free assays, extensive mutagenesis analysis and confocal imaging techniques were employed to examine the mechanisms and outcomes of SPRY2 S-acylation. The results presented show that SPRY2 is differentially modified by zDHHC enzymes: zDHHC17 displayed apparent selectivity for Cys-265/268, whereas zDHHC7 and zDHHC3 mediated more expansive S-acylation of the CRD. S-acylation mediated by both zDHHC17 and zDHHC7 required the presence of a novel NDK (Asn-Asp-Lys) motif in the CRD.;Regardless of the modifying enzyme, S-acylation correlated with increased levels of SPRY2 protein, which is linked to an increase in SPRY2 stability. Furthermore, confocal microscopy revealed that S-acylation is also required for efficient plasma membrane targeting. The interaction between SPRY2 and zDHHC17 was further explored and although SPRY2 interacted with the ankyrin repeat (ANK) domain of zDHHC17 through a canonical mechanism, this mode of binding was dispensable for S-acylation. Binding assays suggested the presence of an additional lower affinity interaction site, which might involve amino acid regions 155-290 and/or 106-120 of SPRY2.;Finally, evidence is presented that zDHHC17 forms dimers or higher-order oligomers, which involve ANK-ANK interactions. It is speculated that the formation of these zDHHC17 oligomers might be relevant to the function of the enzyme. Overall, this thesis highlights that S-acylation regulates multiple aspects of SPRY2, including protein stability and plasma membrane targeting. As expression levels and localisation are two fundamental properties of a protein and because alterations in these properties can cause disease, we propose that targeting SPRY2 S-acylation might represent a novel therapeutic strategy in cancer and other diseases.S-acylation is a reversible post-translational modification (PTM) that regulates proteins in several ways, including by modulating trafficking, stability and protein interactions. This PTM is mediated by twenty-three zinc finger DHHC (zDHHC) enzymes that display distinct activity and substrate selectivity profiles. Sprouty (SPRY) proteins are regulators of Receptor Tyrosine Kinase (RTK) signalling and play a major role in maintaining cellular homeostasis. Indeed, their deregulation is linked to tumorigenesis, developmental defects and neurological diseases.;The defining feature of SPRY proteins is a large cysteine-rich domain (CRD), which is modified by S-acylation. In this thesis, cell-based and cell-free assays, extensive mutagenesis analysis and confocal imaging techniques were employed to examine the mechanisms and outcomes of SPRY2 S-acylation. The results presented show that SPRY2 is differentially modified by zDHHC enzymes: zDHHC17 displayed apparent selectivity for Cys-265/268, whereas zDHHC7 and zDHHC3 mediated more expansive S-acylation of the CRD. S-acylation mediated by both zDHHC17 and zDHHC7 required the presence of a novel NDK (Asn-Asp-Lys) motif in the CRD.;Regardless of the modifying enzyme, S-acylation correlated with increased levels of SPRY2 protein, which is linked to an increase in SPRY2 stability. Furthermore, confocal microscopy revealed that S-acylation is also required for efficient plasma membrane targeting. The interaction between SPRY2 and zDHHC17 was further explored and although SPRY2 interacted with the ankyrin repeat (ANK) domain of zDHHC17 through a canonical mechanism, this mode of binding was dispensable for S-acylation. Binding assays suggested the presence of an additional lower affinity interaction site, which might involve amino acid regions 155-290 and/or 106-120 of SPRY2.;Finally, evidence is presented that zDHHC17 forms dimers or higher-order oligomers, which involve ANK-ANK interactions. It is speculated that the formation of these zDHHC17 oligomers might be relevant to the function of the enzyme. Overall, this thesis highlights that S-acylation regulates multiple aspects of SPRY2, including protein stability and plasma membrane targeting. As expression levels and localisation are two fundamental properties of a protein and because alterations in these properties can cause disease, we propose that targeting SPRY2 S-acylation might represent a novel therapeutic strategy in cancer and other diseases
Investigating tangible and experiential design priorities for people living with chronic medical hair loss (alopecia), when acquiring, wearing, cleaning, maintaining and disposing of hair prosthesis (wigs)
No full textThis study concentrates on the detailed topics of ‘wig(s)’ and ‘alopecia’ collectively. Currently there is no cure for Alopecia areata (AA). However, it is responsible for 2% of dermatology clinic visits in the UK and USA, and one of the six most economicallyburdensome skin conditions; from an estimated range of 3,000. Wigs are reported as “useful in the management of AA” by the British Association of Dermatologists (BAD). Yet, there is no published evidence to suggest wigs are effective in helping people copewith AA or understanding of their efficacy as a treatment. Through a systematic literature review, the study identified a paucity of publishedinformation on each area respectively. In order to fill in these knowledge gaps, this study adopted a sequential-exploratory and multiphase design to generate and answer research questions, rather than testing a hypothesis or assumptions. The research was framed using Creswell & Plano Clark’s sequential mixed methods (2009 & 2011) and Norman’s user centred design (UCD). Firstly, conducting 2 focus groups and 14 semi-structured interviews. Identifying end users ‘priorities’ and ‘problems’ when acquiring, wearing, maintaining, and disposing of wigs. These qualitative findings informed the development of a detailed online questionnaire (n.53). In turn the numerical results were used to inform the scientific analysis of 6 popular wigs (A-F), benchmarked against virgin human hair (G) and raw polyacrylonitrile filament (H). The rigorous and comprehensive research identified a number of tangible and experiential relationships impacting on end users, including, “Durability” issues with wigswhen exposed to heat (cooking). 92% reported heat as their highest priority and problem. Fibre testing confirmed exposure to heat would intrinsically alter aesthetics of polymeric filaments due to material degradation (Ty) and irreversible damage (Tg), making fibres “noticeable’ (unrealistic) to onlookers. Remarkably, all the filaments tested had similar fibre compositions, with subtle variations in their cross sections, topographical or chemical profiles. Controversially, there is no British standard (BS) for wigs, but there is for dolls hair, meaning quality assurance of wigs is not always guaranteed. Therefore, if wigs are to be used in the management of AA a productstandard should be introduced, accounting for end users priorities and problems (UCD). This study is the first (UK) questionnaire to capture and identify wig priorities and problems for end users’ with alopecia. First to present micro and macro comparison tables for 6 commercial wigs, measured against reference samples. First to presentthermal profiling (DSC, DMA, and hotplate) and micro and macro analysis of wig filaments, including a simulation, opening an oven door. This research contributed to 5 academic publications in areas of alopecia and wigs, several public engagement workshops including an exhibition at the Glasgow Science Centre, “Body Works”. Its contributions to knowledge include: 46 design recommendations covering Manufacture, Acquiring, Wearing, Maintaining & Cleaning.22 suggestions for future research. Creation of sustainable business models for wig materials. Summary tables outlining compilation of different types of cranial alopecia and available treatments; with benefits and side-effects. Plus, detailed understanding of wigcomponents, their supply-chains, manufacture, and state-of-the-art.This study concentrates on the detailed topics of ‘wig(s)’ and ‘alopecia’ collectively. Currently there is no cure for Alopecia areata (AA). However, it is responsible for 2% of dermatology clinic visits in the UK and USA, and one of the six most economicallyburdensome skin conditions; from an estimated range of 3,000. Wigs are reported as “useful in the management of AA” by the British Association of Dermatologists (BAD). Yet, there is no published evidence to suggest wigs are effective in helping people copewith AA or understanding of their efficacy as a treatment. Through a systematic literature review, the study identified a paucity of publishedinformation on each area respectively. In order to fill in these knowledge gaps, this study adopted a sequential-exploratory and multiphase design to generate and answer research questions, rather than testing a hypothesis or assumptions. The research was framed using Creswell & Plano Clark’s sequential mixed methods (2009 & 2011) and Norman’s user centred design (UCD). Firstly, conducting 2 focus groups and 14 semi-structured interviews. Identifying end users ‘priorities’ and ‘problems’ when acquiring, wearing, maintaining, and disposing of wigs. These qualitative findings informed the development of a detailed online questionnaire (n.53). In turn the numerical results were used to inform the scientific analysis of 6 popular wigs (A-F), benchmarked against virgin human hair (G) and raw polyacrylonitrile filament (H). The rigorous and comprehensive research identified a number of tangible and experiential relationships impacting on end users, including, “Durability” issues with wigswhen exposed to heat (cooking). 92% reported heat as their highest priority and problem. Fibre testing confirmed exposure to heat would intrinsically alter aesthetics of polymeric filaments due to material degradation (Ty) and irreversible damage (Tg), making fibres “noticeable’ (unrealistic) to onlookers. Remarkably, all the filaments tested had similar fibre compositions, with subtle variations in their cross sections, topographical or chemical profiles. Controversially, there is no British standard (BS) for wigs, but there is for dolls hair, meaning quality assurance of wigs is not always guaranteed. Therefore, if wigs are to be used in the management of AA a productstandard should be introduced, accounting for end users priorities and problems (UCD). This study is the first (UK) questionnaire to capture and identify wig priorities and problems for end users’ with alopecia. First to present micro and macro comparison tables for 6 commercial wigs, measured against reference samples. First to presentthermal profiling (DSC, DMA, and hotplate) and micro and macro analysis of wig filaments, including a simulation, opening an oven door. This research contributed to 5 academic publications in areas of alopecia and wigs, several public engagement workshops including an exhibition at the Glasgow Science Centre, “Body Works”. Its contributions to knowledge include: 46 design recommendations covering Manufacture, Acquiring, Wearing, Maintaining & Cleaning.22 suggestions for future research. Creation of sustainable business models for wig materials. Summary tables outlining compilation of different types of cranial alopecia and available treatments; with benefits and side-effects. Plus, detailed understanding of wigcomponents, their supply-chains, manufacture, and state-of-the-art
Development of numerical and data models for the support of digital twins in offshore wind engineering
Get PDFAs offshore wind farms grow there is a continued demand for reduced costs. Maintenance costs and downtime can be reduced through greater information on the asset in relation to its operational loads and structural resistance to damage and so there is an increasing interest in digital twin technologies. Through digital twins, an operational asset can be replicated computationally, thus providing more information. Modelling these aspects requires a wide variety of models in different fields. To advance the feasibility of digital twin technology this thesis aims to develop the multi-disciplinary set of modelling domains which help form the basis of future digital twins. Throughout this work, results have been validated against operational data recorded from sensors on offshore structures. This has provided value and confidence to the results as it shows how well the mix of state-of-the art models compare to real world engineering systems.This research presents a portfolio of five research areas which have been published in a mix of peer-reviewed journal articles and conference papers. These areas are: 1) A computational fluid dynamics (CFD) model of an offshore wind farm conducted using a modified solver in the opensource software. This work implements actuator disk turbine models and uses Reynolds averaged Naiver Stokes approaches to represent the turbulence. This investigates the impact of modelling choices and demonstrates the impact of varied model parameters. The results are compared to operational site data and the modelling errors are quantified. There is good agreement between the models and site data. 2) An expansion on traditional CFD approaches through incorporating machine learning (ML). These ML models are used to approximate the results of the CFD and thereby allow for further analysis which retains the fidelity of CFD at comparatively negligible computational cost. The results are compared to operational site data and the errors at each step are quantified for validation. 3) A time-series forecasting of weather variables based on past measured data. A novel approach for forecasting time-series is developed and compared to two existing methods: Markov-Chains and Gradient Boosting. While this new method is more complex and requires more time to train, it has the desirable feature of incorporating seasonality at multiple timescales and thus providing a more representative time-series. 4) An investigation of the change in modal parameters in an offshore wind jacket structure from damages or from changing operational conditions. In this work the detailed design model of the structure from Ramboll is used. This section relates the measurable modal parameters to the operational condition through a modelling approach. 5) A study conducted using accelerometer data from an Offshore Substation located in a wind farm site. Operational data from 12 accelerometers is used to investigate the efficacy of several potential sensor layouts and therefore to quantify the consequence of placement decisions.The results of these developments are an overall improvement in the modelling approaches necessary towards the realisation of digital twins as well as useful development in each of the component areas. Both areas related to wind loading as well as structural dynamics have been related to operational data. The validation of this link between the measured and the modelled domains facilitates operators and those in maintenance in gaining more information and greater insights into the conditions of their assets.As offshore wind farms grow there is a continued demand for reduced costs. Maintenance costs and downtime can be reduced through greater information on the asset in relation to its operational loads and structural resistance to damage and so there is an increasing interest in digital twin technologies. Through digital twins, an operational asset can be replicated computationally, thus providing more information. Modelling these aspects requires a wide variety of models in different fields. To advance the feasibility of digital twin technology this thesis aims to develop the multi-disciplinary set of modelling domains which help form the basis of future digital twins. Throughout this work, results have been validated against operational data recorded from sensors on offshore structures. This has provided value and confidence to the results as it shows how well the mix of state-of-the art models compare to real world engineering systems.This research presents a portfolio of five research areas which have been published in a mix of peer-reviewed journal articles and conference papers. These areas are: 1) A computational fluid dynamics (CFD) model of an offshore wind farm conducted using a modified solver in the opensource software. This work implements actuator disk turbine models and uses Reynolds averaged Naiver Stokes approaches to represent the turbulence. This investigates the impact of modelling choices and demonstrates the impact of varied model parameters. The results are compared to operational site data and the modelling errors are quantified. There is good agreement between the models and site data. 2) An expansion on traditional CFD approaches through incorporating machine learning (ML). These ML models are used to approximate the results of the CFD and thereby allow for further analysis which retains the fidelity of CFD at comparatively negligible computational cost. The results are compared to operational site data and the errors at each step are quantified for validation. 3) A time-series forecasting of weather variables based on past measured data. A novel approach for forecasting time-series is developed and compared to two existing methods: Markov-Chains and Gradient Boosting. While this new method is more complex and requires more time to train, it has the desirable feature of incorporating seasonality at multiple timescales and thus providing a more representative time-series. 4) An investigation of the change in modal parameters in an offshore wind jacket structure from damages or from changing operational conditions. In this work the detailed design model of the structure from Ramboll is used. This section relates the measurable modal parameters to the operational condition through a modelling approach. 5) A study conducted using accelerometer data from an Offshore Substation located in a wind farm site. Operational data from 12 accelerometers is used to investigate the efficacy of several potential sensor layouts and therefore to quantify the consequence of placement decisions.The results of these developments are an overall improvement in the modelling approaches necessary towards the realisation of digital twins as well as useful development in each of the component areas. Both areas related to wind loading as well as structural dynamics have been related to operational data. The validation of this link between the measured and the modelled domains facilitates operators and those in maintenance in gaining more information and greater insights into the conditions of their assets
Translation and feasibility testing of the Healthy Habits Happy Homes (4H) Intervention to Scotland (4HS)
No full textBackground: Childhood obesity is complex disease that will not be solved with anysingle intervention. There is an inequality in obesity risk for children growing up inthe most deprived communities and research should be undertaken, alongsidemarginalised communities. This thesis reports on the translation and feasibility testingof an existing, pre-school obesity prevention intervention, Healthy Habits HappyHomes (4H) alongside a community marginalised by poverty in Dundee, Scotland(4HS).Methods: Five studies, in the form of two published papers and three manuscripts arepresented, centred around a logic model (LM) and evolving Theory of Change (TOC),conceptualising the study with a systems lens. Three key stages of feasibility studydesign and development were reported and evaluation of process utilised the RE-AIMframework. Mixed methods were utilised in order to characterise families and suitablyreport study outcomes against TOC with each research phase appraised againstMedical Research Council (MRC) core elements.Results: n=8 activities, n=5 short-term outcomes, n=4 intermediate outcomes wereoutlined in a LM presented in study one. The co-produced, translated 4HS wasfeasible to deliver, pragmatic and demonstrated good fidelity to MotivationalInterviewing (MI). Participant families valued home visits and positive, trustingrelationships which facilitated engagement and positive behaviour change. TOCevolved through insights from community stakeholder and offered a reportingmechanism for 4HS outputs that informed 4HS implementation in routine NHSpractice. Conclusions: The 4HS study design and translational processes enabled suitableunderstanding of key contextual factors including participant characteristics,development of appropriate feasibility outcome reporting mechanisms andpreliminary data. When these data are combined it enables consideration of thecontribution the 4HS study makes to the wider, local, childhood obesity system.Integrating 4HS into an existing NHS service was tested during the Covid-19pandemic, leaving it open to a future research and / or practice-based directionBackground: Childhood obesity is complex disease that will not be solved with anysingle intervention. There is an inequality in obesity risk for children growing up inthe most deprived communities and research should be undertaken, alongsidemarginalised communities. This thesis reports on the translation and feasibility testingof an existing, pre-school obesity prevention intervention, Healthy Habits HappyHomes (4H) alongside a community marginalised by poverty in Dundee, Scotland(4HS).Methods: Five studies, in the form of two published papers and three manuscripts arepresented, centred around a logic model (LM) and evolving Theory of Change (TOC),conceptualising the study with a systems lens. Three key stages of feasibility studydesign and development were reported and evaluation of process utilised the RE-AIMframework. Mixed methods were utilised in order to characterise families and suitablyreport study outcomes against TOC with each research phase appraised againstMedical Research Council (MRC) core elements.Results: n=8 activities, n=5 short-term outcomes, n=4 intermediate outcomes wereoutlined in a LM presented in study one. The co-produced, translated 4HS wasfeasible to deliver, pragmatic and demonstrated good fidelity to MotivationalInterviewing (MI). Participant families valued home visits and positive, trustingrelationships which facilitated engagement and positive behaviour change. TOCevolved through insights from community stakeholder and offered a reportingmechanism for 4HS outputs that informed 4HS implementation in routine NHSpractice. Conclusions: The 4HS study design and translational processes enabled suitableunderstanding of key contextual factors including participant characteristics,development of appropriate feasibility outcome reporting mechanisms andpreliminary data. When these data are combined it enables consideration of thecontribution the 4HS study makes to the wider, local, childhood obesity system.Integrating 4HS into an existing NHS service was tested during the Covid-19pandemic, leaving it open to a future research and / or practice-based directio
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