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Biocompatibility assessment of a sol-gel modified electrospun ventricular shunt catheter
Get PDFPreviously held under moratorium from 13th October 2020 until 13th October 2022.Hydrocephalus is a clinical condition that usually originates froma reduced passage of cerebrospinal fluid from one brain ventricle toanother. The main procedure to treat this condition involves the insertion of a shunt catheter to bypass the blockage and allow the CSFto flow from the ventricles, thus avoiding a possible build-up of intracranial pressure. Such catheters, which are commonly made frommedical grade silicone, are known to be affected by mechanical failures, infection and blockage owing to cerebral tissue infiltration andbacterial colonisation.To decrease cell adhesion and at the same time increase resistanceto bacterial colonisation, medical grade polyurethane was modifiedwith the addition of inorganic modifiers (titanium and zinc) via a solgel process.Both titanium and zinc were successfully incorporated into the polyurethane in an amorphous form, having a strong impact on the microstructure of the fibres, as the presence of the inorganic phase affects the degree of segregation of hard and soft segments typical ofpolyurethanes, and changes the diameter size and distribution of thefibres, with modified materials exhibiting a narrower diameter distribution. Titanium is well dispersed within the fibres, while zinc tendsto segregate on the surface. All electrospun materials are effective atabsorbing fluid quickly.The co-action of morphological factors and chemistry is effective incontrolling cell adhesion and bacterial colonisation. Upon exposure tohuman immortalised astrocyte cultures, modified electrospun materials exhibit a significantly lower viability than the positive control, anda higher apoptotic rate than the negative control (PDMS). Preliminaryresults suggest that cell adhesion is lower for materials with smallerfibre diameters.Furthermore, results from bacterial colonisation studies show thatnanostructured surfaces are effective in controlling and reducing Staphylococcus aureus colonisation (1 log₁₀ unit reduction), as compared tothe standard silicone.Hydrocephalus is a clinical condition that usually originates froma reduced passage of cerebrospinal fluid from one brain ventricle toanother. The main procedure to treat this condition involves the insertion of a shunt catheter to bypass the blockage and allow the CSFto flow from the ventricles, thus avoiding a possible build-up of intracranial pressure. Such catheters, which are commonly made frommedical grade silicone, are known to be affected by mechanical failures, infection and blockage owing to cerebral tissue infiltration andbacterial colonisation.To decrease cell adhesion and at the same time increase resistanceto bacterial colonisation, medical grade polyurethane was modifiedwith the addition of inorganic modifiers (titanium and zinc) via a solgel process.Both titanium and zinc were successfully incorporated into the polyurethane in an amorphous form, having a strong impact on the microstructure of the fibres, as the presence of the inorganic phase affects the degree of segregation of hard and soft segments typical ofpolyurethanes, and changes the diameter size and distribution of thefibres, with modified materials exhibiting a narrower diameter distribution. Titanium is well dispersed within the fibres, while zinc tendsto segregate on the surface. All electrospun materials are effective atabsorbing fluid quickly.The co-action of morphological factors and chemistry is effective incontrolling cell adhesion and bacterial colonisation. Upon exposure tohuman immortalised astrocyte cultures, modified electrospun materials exhibit a significantly lower viability than the positive control, anda higher apoptotic rate than the negative control (PDMS). Preliminaryresults suggest that cell adhesion is lower for materials with smallerfibre diameters.Furthermore, results from bacterial colonisation studies show thatnanostructured surfaces are effective in controlling and reducing Staphylococcus aureus colonisation (1 log₁₀ unit reduction), as compared tothe standard silicone
Acid gas removal from natural gas using ionic liquids
Get PDFThe growth in demand for natural gas accounted for almost half the increase in global energy consumption in 2018 and is projected to increase by more than 10% over the next five years. This is due to its abundancy, efficiency and lower carbon content compared to oil and coal. However, raw gas contains undesirable components, such as hydrogen sulphide and carbon dioxide, which must be removed before its delivery to end users because of their toxicity, corrosivity, flammability and poor heating value.;Various technologies have been used for acid gas removal. Amine-based absorption is the most widely used technique; however, they are corrosive, volatile, degrade at high temperatures and highly energy intensive to regenerate. This study aims to improve pre-existing amine processes by reducing their energy consumption and environmental impact through the use of ionic liquids (ILs) and their blend with other physical solvents as an alternative to amines.;The consequences of replacing an amine with ILs or a blend of ILs with other physical solvent in an existing amine unit are examined and found to be promising. A thermodynamic description of the IL mixtures needed to be developed to examine their use to replace amine solutions. The perturbed chain statistical association fluid theory (PC-SAFT) is selected as the thermodynamic model to represent the vapour liquid equilibrium of acid gases-IL systems.;The solubility of gases in ILs was successfully described without the need for empirical binary interaction parameters, as was required in previous studies. Up to 47% and 7% of the regeneration energy and the total annual cost, respectively, were saved by using IL instead of amine, while up to 40% and 27% of the regeneration energy and the total annual cost, respectively, were saved by using a blend of IL with other physical solvent.The growth in demand for natural gas accounted for almost half the increase in global energy consumption in 2018 and is projected to increase by more than 10% over the next five years. This is due to its abundancy, efficiency and lower carbon content compared to oil and coal. However, raw gas contains undesirable components, such as hydrogen sulphide and carbon dioxide, which must be removed before its delivery to end users because of their toxicity, corrosivity, flammability and poor heating value.;Various technologies have been used for acid gas removal. Amine-based absorption is the most widely used technique; however, they are corrosive, volatile, degrade at high temperatures and highly energy intensive to regenerate. This study aims to improve pre-existing amine processes by reducing their energy consumption and environmental impact through the use of ionic liquids (ILs) and their blend with other physical solvents as an alternative to amines.;The consequences of replacing an amine with ILs or a blend of ILs with other physical solvent in an existing amine unit are examined and found to be promising. A thermodynamic description of the IL mixtures needed to be developed to examine their use to replace amine solutions. The perturbed chain statistical association fluid theory (PC-SAFT) is selected as the thermodynamic model to represent the vapour liquid equilibrium of acid gases-IL systems.;The solubility of gases in ILs was successfully described without the need for empirical binary interaction parameters, as was required in previous studies. Up to 47% and 7% of the regeneration energy and the total annual cost, respectively, were saved by using IL instead of amine, while up to 40% and 27% of the regeneration energy and the total annual cost, respectively, were saved by using a blend of IL with other physical solvent
4D CT based analysis of knee kinematics
No full textIntroduction: Total Knee Arthroplasty, which is the last resort of treatment for osteoarthritis, is aimed at restoring the functional anatomy of the knee. Despite the recent improvements in surgical techniques, limited range of motion, postoperative instability and malalignment still hinder the restoration of the knee's original function. Bearing in mind that stability, range of motion and alignment are all directly correlated with the kinematics of the knee, then focus should be given to understanding the underlying knee mechanics to be able to restore the native kinematics. Contemporarily, routine clinical practice still relies on 2-dimensional standing X-rays to diagnose the underlying knee pathology, which is limited in terms of accurately assessing the essential knee kinematics.;Aims: Utilise the innovative 4D CT scanners to capture the articulation of healthy and replaced knees. Develop a bespoke proof-of-concept software which utilises the 4D CT data and extracts three principal kinematic outcome measures. Extract the kinematics of ten participants and analyse the data to address two low-powered pilot studies.;Methods: A 4D CT scanning protocol was developed to record a flexion-extension exercise dynamically. The bespoke software, developed in MATLAB, extracted the three principal kinematic outcome measures for the ten participants who were scanned. The extracted kinematic data for the control participants was analysed to identify the applicable range of motion for specific flexion-extension axes of the knee, via the determination of kinematic crosstalk. The patient data was used to analyse the mobility of fixed-bearing and mobile bearing implants.;Results: The software successfully extracted the six-degrees-of-freedom kinematics, performed a contact point analysis and identified the axial centre of rotation of both healthy and replaced knees. The control data identified the Trans Epicondylar Axis as being applicable for the Extension (-5º to 10º of flexion) and Transition (10º to 30º of flexion) phases of flexion while the Geometric Centre Axis being applicable for the Flexion phase (30º to 120º of flexion). The participant data did not identify any variation in the level of mobility between the fixed-bearing and mobile-bearing knees.;Conclusion: The feasibility of the developed kinematic analysis software was proven as a viable alternative, via its implementation on the healthy and replaced knees. The kinematic crosstalk of specific flexion-extension axes was shown to vary depending on the flexion angle. Mobile-bearing knees do not provide patients with extra mobility over their fixed bearing counterparts.Introduction: Total Knee Arthroplasty, which is the last resort of treatment for osteoarthritis, is aimed at restoring the functional anatomy of the knee. Despite the recent improvements in surgical techniques, limited range of motion, postoperative instability and malalignment still hinder the restoration of the knee's original function. Bearing in mind that stability, range of motion and alignment are all directly correlated with the kinematics of the knee, then focus should be given to understanding the underlying knee mechanics to be able to restore the native kinematics. Contemporarily, routine clinical practice still relies on 2-dimensional standing X-rays to diagnose the underlying knee pathology, which is limited in terms of accurately assessing the essential knee kinematics.;Aims: Utilise the innovative 4D CT scanners to capture the articulation of healthy and replaced knees. Develop a bespoke proof-of-concept software which utilises the 4D CT data and extracts three principal kinematic outcome measures. Extract the kinematics of ten participants and analyse the data to address two low-powered pilot studies.;Methods: A 4D CT scanning protocol was developed to record a flexion-extension exercise dynamically. The bespoke software, developed in MATLAB, extracted the three principal kinematic outcome measures for the ten participants who were scanned. The extracted kinematic data for the control participants was analysed to identify the applicable range of motion for specific flexion-extension axes of the knee, via the determination of kinematic crosstalk. The patient data was used to analyse the mobility of fixed-bearing and mobile bearing implants.;Results: The software successfully extracted the six-degrees-of-freedom kinematics, performed a contact point analysis and identified the axial centre of rotation of both healthy and replaced knees. The control data identified the Trans Epicondylar Axis as being applicable for the Extension (-5º to 10º of flexion) and Transition (10º to 30º of flexion) phases of flexion while the Geometric Centre Axis being applicable for the Flexion phase (30º to 120º of flexion). The participant data did not identify any variation in the level of mobility between the fixed-bearing and mobile-bearing knees.;Conclusion: The feasibility of the developed kinematic analysis software was proven as a viable alternative, via its implementation on the healthy and replaced knees. The kinematic crosstalk of specific flexion-extension axes was shown to vary depending on the flexion angle. Mobile-bearing knees do not provide patients with extra mobility over their fixed bearing counterparts
Active control of femtosatellite swarms for synthetic aperture rada
Get PDFRecent developments in electronics and technology have pushed miniaturised satellites to the femto-scale, which feature a low mass between 10 to 100 g. Although femtosatellites have been proven as a feasible concept, most designs are limited by sensor capacity and mission lifetime due to the lack of environmental protection and onboard propellent. In this thesis, a novel concept of using femtosatellites for Earth remote sensing missions has been proposed. In particular, a novel femtosatellite concept based on the utilisation of solar radiation pressure is introduced together with an Earth remote sensing mission concept. The prototype femtosatellite design features a high area-to-mass ratio to maximise solar radiation pressure for orbit control. A flexible base material enables self-release when loaded with pre-applied tension to reduce the complexity of the carrier spacecraft release mechanism. Its flat-bubble design also provides basic thermal and radiation protection. In addition to an antenna for communication to the carrier spacecraft, the prototype design includes a separate antennae for radar applications, the design of which will vary depending on the mission requirement. A hardware design is also provided for such a femtosatellite concept and performance is evaluated for an Earth remote sensing mission. The mission concept utilises swarms of femtosatellites as receivers for enhanced radar mission. A 'dawn-dusk' Sun-synchronous orbit has been chosen to maximise solar radiation pressure for orbit control and power generation. The orbital dynamics of the proposed femtosatellite concept is investigated and a novel active orbit control strategy for relative motion control with solar radiation pressure is developed. This control strategy demonstrates the feasibility of using solar radiation pressure for swarm control, which can be modulated by using electrochromic panels, to achieve the active orbit control of individual femtosatellites. This will extend the femtosatellite swarm mission capability and lifetime. The femtosatellite swarm deployment evolution is also provided to demonstrate the active orbit control strategy. The performance of the femtosatellite swarm Earth remote sensing mission is evaluated and characterised by the number of femtosatellites, the receiver signal-to-noise ratio and the accuracy of positioning. These research results demonstrate the feasibility of using swarms of femtosatellites for Earth remote sensing. In addition, by adapting the radar signal processing algorithm, on-orbit targets could be detected. This is demonstrated by imaging the international space station and mock space debris for space situational awareness applications.Recent developments in electronics and technology have pushed miniaturised satellites to the femto-scale, which feature a low mass between 10 to 100 g. Although femtosatellites have been proven as a feasible concept, most designs are limited by sensor capacity and mission lifetime due to the lack of environmental protection and onboard propellent. In this thesis, a novel concept of using femtosatellites for Earth remote sensing missions has been proposed. In particular, a novel femtosatellite concept based on the utilisation of solar radiation pressure is introduced together with an Earth remote sensing mission concept. The prototype femtosatellite design features a high area-to-mass ratio to maximise solar radiation pressure for orbit control. A flexible base material enables self-release when loaded with pre-applied tension to reduce the complexity of the carrier spacecraft release mechanism. Its flat-bubble design also provides basic thermal and radiation protection. In addition to an antenna for communication to the carrier spacecraft, the prototype design includes a separate antennae for radar applications, the design of which will vary depending on the mission requirement. A hardware design is also provided for such a femtosatellite concept and performance is evaluated for an Earth remote sensing mission. The mission concept utilises swarms of femtosatellites as receivers for enhanced radar mission. A 'dawn-dusk' Sun-synchronous orbit has been chosen to maximise solar radiation pressure for orbit control and power generation. The orbital dynamics of the proposed femtosatellite concept is investigated and a novel active orbit control strategy for relative motion control with solar radiation pressure is developed. This control strategy demonstrates the feasibility of using solar radiation pressure for swarm control, which can be modulated by using electrochromic panels, to achieve the active orbit control of individual femtosatellites. This will extend the femtosatellite swarm mission capability and lifetime. The femtosatellite swarm deployment evolution is also provided to demonstrate the active orbit control strategy. The performance of the femtosatellite swarm Earth remote sensing mission is evaluated and characterised by the number of femtosatellites, the receiver signal-to-noise ratio and the accuracy of positioning. These research results demonstrate the feasibility of using swarms of femtosatellites for Earth remote sensing. In addition, by adapting the radar signal processing algorithm, on-orbit targets could be detected. This is demonstrated by imaging the international space station and mock space debris for space situational awareness applications
Generative design of robust modular system architectures
Get PDFModern engineering systems are frequently formed from complex networks of interwoven technological solutions, whose functions combine to enable key functions in the society: the defence of nations, the transport of people, the transmission of energy. The creation of such systems requires a detailed understanding of how the components interact both physically and functionally as a whole. However, while physical and functional connections (e.g. lines of power and control) can be defined, characterising a system's level of robustness when subjected to different disruptions is more challenging.;Essentially although many system architectures aim to create a degree of redundancy, that ensures robust operation under disruptions, it's difficult to quantify the level of robustness and so to evaluate and select the right system architecture option during the initial stage of the design.;This problem can be observed in many different domains of distributed engineering systems i.e. systems dictated by their configuration of source and sink components, structured in such a way as to provide a specific set of functions. Because of this, architects often do not consider, how the definition of the modular configuration (i.e. the degree of modularity) affects the overall robustness of the system.;Indeed, the choice of new system architectures is often dictated by subject matter experts and previous designs during the initial design phase. This leads to limited exploration, analysis and evaluation of potential system architecture design options, and selection of the system architecture that proves to be balanced between robustness and modularity at the beginning of system development.;Motivated by this need this thesis proposes a 'Robust Modular Generation and Assessment' (RoMoGA) methodology that combines a network tool (used to create alternate system architecture options) with a robustness and modularity evaluation metrics (that quantifies the robustness and modularity of each candidate system architecture option). The methodology has been used in case studies of three naval ship distributed systems and an explorative application was performed though experiments.;The industrial evaluation was based on semi-structured interviews and industrial design practices. The findings of the evaluation highlighted the existence of trade-offs between redundancy, modularity and robustness, the influence of the type of redundancy, the effects of the type of disruptions and effects of patterns and topological features. The evaluation part of the study led to redesign and update proposals for the original naval system designs, which the experts have assessed as rational and improved design solutions. The thesis reflects on the limitations of the proposed methodology and makes recommendations for future work.Modern engineering systems are frequently formed from complex networks of interwoven technological solutions, whose functions combine to enable key functions in the society: the defence of nations, the transport of people, the transmission of energy. The creation of such systems requires a detailed understanding of how the components interact both physically and functionally as a whole. However, while physical and functional connections (e.g. lines of power and control) can be defined, characterising a system's level of robustness when subjected to different disruptions is more challenging.;Essentially although many system architectures aim to create a degree of redundancy, that ensures robust operation under disruptions, it's difficult to quantify the level of robustness and so to evaluate and select the right system architecture option during the initial stage of the design.;This problem can be observed in many different domains of distributed engineering systems i.e. systems dictated by their configuration of source and sink components, structured in such a way as to provide a specific set of functions. Because of this, architects often do not consider, how the definition of the modular configuration (i.e. the degree of modularity) affects the overall robustness of the system.;Indeed, the choice of new system architectures is often dictated by subject matter experts and previous designs during the initial design phase. This leads to limited exploration, analysis and evaluation of potential system architecture design options, and selection of the system architecture that proves to be balanced between robustness and modularity at the beginning of system development.;Motivated by this need this thesis proposes a 'Robust Modular Generation and Assessment' (RoMoGA) methodology that combines a network tool (used to create alternate system architecture options) with a robustness and modularity evaluation metrics (that quantifies the robustness and modularity of each candidate system architecture option). The methodology has been used in case studies of three naval ship distributed systems and an explorative application was performed though experiments.;The industrial evaluation was based on semi-structured interviews and industrial design practices. The findings of the evaluation highlighted the existence of trade-offs between redundancy, modularity and robustness, the influence of the type of redundancy, the effects of the type of disruptions and effects of patterns and topological features. The evaluation part of the study led to redesign and update proposals for the original naval system designs, which the experts have assessed as rational and improved design solutions. The thesis reflects on the limitations of the proposed methodology and makes recommendations for future work
Synthesis and characterisation of new tetrathiafulvalene-oligofluorene derivatives for moisture indicators
Get PDFThe term 'smart materials' refers to a category of materials that are able to dynamically respond to external stimuli through a change in physical and/or chemical properties. The versatility afforded by organic materials makes them attractive candidates in the development of new sensing materials. An in-depth understanding of the structure property relationships that drive a sensing material is a necessity in understanding device operation and reliably predicting their performance. Chapter 1 provides an overview of organic stimuli responsive materials and the types of physical properties that can induce a response in such materials. Chapter 1 further introduces the operating principles of sensors and their applications. Chapter 2 provides an introduction to the development of the novel hexylatedoligofluorene-thiophene systems wherein versatile 1,3-dithiole-2-one moiety is incorporated into the centre of the oligofluorene systems. The chapter follows a synthetic strategy used as a way to increase the dimensionality of oligofluorenesystems and discusses the influence of the synthetic strategy vis-à-vis yield and reproducibility of the systems. Chapter 2 further looks at the impact of the core uniton the photophysical behaviour of the oligofluorene spores and discusses the changes in the thermal and electronic properties of the new oligofluorene-thiophene systems as a consequence of the core unit. Chapter 3 discusses the development of new star-shaped oligofluorene-thiophene systems wherein redox-active dithiophene-tetrathiafulvalene is used as a core unit, providing an increase in dimensionality to a plurality of hexylated oligofluorenespores. The synthesis and properties of the oligofluorene systems are discussed. The photophysical behaviour, thermal and electronic properties of the new systems are investigated. Furthermore the core system displayed upon oxidation interesting features as fluorescence moisture indicator and are further investigated wherein the proof of concept is visible to the naked eye. The experimental procedures of chapters 2-3 are presented in chapter 4The term 'smart materials' refers to a category of materials that are able to dynamically respond to external stimuli through a change in physical and/or chemical properties. The versatility afforded by organic materials makes them attractive candidates in the development of new sensing materials. An in-depth understanding of the structure property relationships that drive a sensing material is a necessity in understanding device operation and reliably predicting their performance. Chapter 1 provides an overview of organic stimuli responsive materials and the types of physical properties that can induce a response in such materials. Chapter 1 further introduces the operating principles of sensors and their applications. Chapter 2 provides an introduction to the development of the novel hexylatedoligofluorene-thiophene systems wherein versatile 1,3-dithiole-2-one moiety is incorporated into the centre of the oligofluorene systems. The chapter follows a synthetic strategy used as a way to increase the dimensionality of oligofluorenesystems and discusses the influence of the synthetic strategy vis-à-vis yield and reproducibility of the systems. Chapter 2 further looks at the impact of the core uniton the photophysical behaviour of the oligofluorene spores and discusses the changes in the thermal and electronic properties of the new oligofluorene-thiophene systems as a consequence of the core unit. Chapter 3 discusses the development of new star-shaped oligofluorene-thiophene systems wherein redox-active dithiophene-tetrathiafulvalene is used as a core unit, providing an increase in dimensionality to a plurality of hexylated oligofluorenespores. The synthesis and properties of the oligofluorene systems are discussed. The photophysical behaviour, thermal and electronic properties of the new systems are investigated. Furthermore the core system displayed upon oxidation interesting features as fluorescence moisture indicator and are further investigated wherein the proof of concept is visible to the naked eye. The experimental procedures of chapters 2-3 are presented in chapter
Epidemics under environmental noise described by stochastic SIS model
No full textIn this research, three different stochastic SIS models are concerned with different environmental noises. We firstly introduce two perturbations in the classical deterministic susceptible-infected-susceptible (SIS) epidemic model. Gray et al. [1] in 2011 used a perturbation on β in SIS model. Based on their previous work, we consider another perturbation on the parameter µ + ɣ and formulate the original model as a stochastic differential equation (SDE) with two independent Brownian motions for the number of infected population.;We then prove that our model has a unique and bounded global solution I(t). Also we establish conditions for extinction and persistence of the infected population I(t). Under the conditions of persistence, we show that there is a unique stationary distribution and derive its mean and variance. Computer simulations illustrate our results and provide evidence to back up our theory. This work is published in JMAA [2].;We then introduce the second model replacing two independent Brownian motions in the first model by two correlated Brownian motions. We consider the two same perturbations in the deterministic SIS model and formulate the original model as a stochastic differential equation (SDE) with two correlated Brownian motions for the number of infected population, based on previous work from Gray et al. in 2011 and Hening's work [3] in 2017. Conditions for the solution to become extinct and persistent are then stated, followed by computer simulations to illustrate the results.;Compared to the formal model, the conditions of extinction are extended after correlation between two white noises is considered. However, we are not able to compute the mean and variance of the stationary distribution.Note that this section has also been published as an article in Nonlinear Dynamics in 2019 [4].;Moreover, we combined the first model with [5] to add telegraph noise by using Markovian switching to generate the third model. Similarly, conditions for extinction and persistence are then given and proved, followed by explanation on the stationary distribution. Computer simulations are clearly illustrated with different sets of parameters, which support our theorems in this chapter. Compared to two previous models, conditions are given based on the overall behaviour of the solution but not separately specified in every state of the Markov chain.In this research, three different stochastic SIS models are concerned with different environmental noises. We firstly introduce two perturbations in the classical deterministic susceptible-infected-susceptible (SIS) epidemic model. Gray et al. [1] in 2011 used a perturbation on β in SIS model. Based on their previous work, we consider another perturbation on the parameter µ + ɣ and formulate the original model as a stochastic differential equation (SDE) with two independent Brownian motions for the number of infected population.;We then prove that our model has a unique and bounded global solution I(t). Also we establish conditions for extinction and persistence of the infected population I(t). Under the conditions of persistence, we show that there is a unique stationary distribution and derive its mean and variance. Computer simulations illustrate our results and provide evidence to back up our theory. This work is published in JMAA [2].;We then introduce the second model replacing two independent Brownian motions in the first model by two correlated Brownian motions. We consider the two same perturbations in the deterministic SIS model and formulate the original model as a stochastic differential equation (SDE) with two correlated Brownian motions for the number of infected population, based on previous work from Gray et al. in 2011 and Hening's work [3] in 2017. Conditions for the solution to become extinct and persistent are then stated, followed by computer simulations to illustrate the results.;Compared to the formal model, the conditions of extinction are extended after correlation between two white noises is considered. However, we are not able to compute the mean and variance of the stationary distribution.Note that this section has also been published as an article in Nonlinear Dynamics in 2019 [4].;Moreover, we combined the first model with [5] to add telegraph noise by using Markovian switching to generate the third model. Similarly, conditions for extinction and persistence are then given and proved, followed by explanation on the stationary distribution. Computer simulations are clearly illustrated with different sets of parameters, which support our theorems in this chapter. Compared to two previous models, conditions are given based on the overall behaviour of the solution but not separately specified in every state of the Markov chain
Investigating the role of corporate social responsibility in achieving a sustainable shipping industry in the aftermath of United Nations 2030 Agenda
Get PDFCorporate social responsibility (CSR) is a concept that has been, gradually, grown and applied to the business world. Although not new to today's business setting, though, still remains difficult to be precisely defined. Broadly, it is assumed that CSR derives from the expectations the society has from enterprises. The term of sustainable development became first known in 'Our Common Future' report, published by the World Commission on Environment and Development (WCED) in 1987.;Though, a remarkable evolution took place at the UN Conference, in September 2015, where the 2030 Agenda and Sustainable Development Goals adopted. Although several studies have been undertaken to illuminate perceptions and practices between CSR and sustainable development in other industries, however, no significant research has yet been undertaken in the tanker and dry bulk maritime context. Especially, in the aftermath of United Nations 2030 Agenda.;As a result, the relationship between CSR and sustainable development remains somehow unexplored. To fill this gap, the present study investigated perceptions, attitudes, drivers, barriers and the relationship between CSR and sustainable development as experienced by shipping companies operating in the tanker and dry bulk shipping sector. To achieve the study aims an overall quantitative approach was adopted. Literature review led to the formulation of six hypotheses, which were tested using data collected by a questionnaire survey. 50 tanker and dry bulk companies, based in 14 countries participated.;Study results indicated that CSR and sustainability awareness and implementation in the tanker and dry shipping sector is at a growing state. Shipping companies have been increasingly responding to latest global regulatory developments and seem to be well adapted. Moreover, stakeholders appeared to exercise a positive influence in maritime companies' decision to adopt CSR. Though, CSR is seen as a voluntary business model, namely, the vehicle to deal with latest sustainability challenges. An integrated management system approach was rated as the most preferred tactic to embrace CSR and achieve sustainability into maritime operations.Corporate social responsibility (CSR) is a concept that has been, gradually, grown and applied to the business world. Although not new to today's business setting, though, still remains difficult to be precisely defined. Broadly, it is assumed that CSR derives from the expectations the society has from enterprises. The term of sustainable development became first known in 'Our Common Future' report, published by the World Commission on Environment and Development (WCED) in 1987.;Though, a remarkable evolution took place at the UN Conference, in September 2015, where the 2030 Agenda and Sustainable Development Goals adopted. Although several studies have been undertaken to illuminate perceptions and practices between CSR and sustainable development in other industries, however, no significant research has yet been undertaken in the tanker and dry bulk maritime context. Especially, in the aftermath of United Nations 2030 Agenda.;As a result, the relationship between CSR and sustainable development remains somehow unexplored. To fill this gap, the present study investigated perceptions, attitudes, drivers, barriers and the relationship between CSR and sustainable development as experienced by shipping companies operating in the tanker and dry bulk shipping sector. To achieve the study aims an overall quantitative approach was adopted. Literature review led to the formulation of six hypotheses, which were tested using data collected by a questionnaire survey. 50 tanker and dry bulk companies, based in 14 countries participated.;Study results indicated that CSR and sustainability awareness and implementation in the tanker and dry shipping sector is at a growing state. Shipping companies have been increasingly responding to latest global regulatory developments and seem to be well adapted. Moreover, stakeholders appeared to exercise a positive influence in maritime companies' decision to adopt CSR. Though, CSR is seen as a voluntary business model, namely, the vehicle to deal with latest sustainability challenges. An integrated management system approach was rated as the most preferred tactic to embrace CSR and achieve sustainability into maritime operations
Sedentary behaviour in office workers, using pragmatic evaluation and the RE-AIM framework to improve potential for impact in the real world
Get PDFBackground: To reduce the burden of disease associated with sedentary behaviour (SB), interventions targeting a reduction in SB in office workers need to have impact in the real world. The thesis aimed to use pragmatic evaluation and the RE-AIM framework to inform and improve understanding of dissemination (reporting) and implementation of interventions targeting SB in office workers in order to guide interventions towards having real world public health impact. Methods: The thesis presents three studies. Study one is an integrative systematic review which aimed to collate and synthesise the published research which reported on at least one aspect of the reach, effectiveness, adoption, implementation and maintenance of an intervention. In the second study the RE-AIM QuEST framework was used to evaluate the potential for further implementation and scale-up of a consultation based single site workplace intervention which aimed to reduce SB. The third study used mixed methods to evaluate a digital intervention in the workplace across multiple workplace settings.;Results: In study one, 61 interventions were included in the systematic review. Reporting within included studies varied across reach (59%), effectiveness (49%), adoption (13%), implementation (44%) and maintenance (8%) and recommendations for improved reporting were given. In study two findings suggested that significant barriers to scale-up existed including lack of management support and time and cost of the intervention. Results from study three suggest that improvements could be made across the RE-AIM framework to facilitate improved effectiveness of the application while maintaining and improving reach, adoption, implementation and maintenance. Conclusion: The studies presented in this thesis will inform and improve the dissemination and implementation of SB interventions in the workplace for impact in the real world. Future research in this area should look to: implement testing for potential public health impact in early phases of research; further investigate the resources for health promotion in the real world and the stakeholder's perceptions of costs and benefits of interventions; investigate the manager's role as a gatekeeper to behaviour change in the workplace.Background: To reduce the burden of disease associated with sedentary behaviour (SB), interventions targeting a reduction in SB in office workers need to have impact in the real world. The thesis aimed to use pragmatic evaluation and the RE-AIM framework to inform and improve understanding of dissemination (reporting) and implementation of interventions targeting SB in office workers in order to guide interventions towards having real world public health impact. Methods: The thesis presents three studies. Study one is an integrative systematic review which aimed to collate and synthesise the published research which reported on at least one aspect of the reach, effectiveness, adoption, implementation and maintenance of an intervention. In the second study the RE-AIM QuEST framework was used to evaluate the potential for further implementation and scale-up of a consultation based single site workplace intervention which aimed to reduce SB. The third study used mixed methods to evaluate a digital intervention in the workplace across multiple workplace settings.;Results: In study one, 61 interventions were included in the systematic review. Reporting within included studies varied across reach (59%), effectiveness (49%), adoption (13%), implementation (44%) and maintenance (8%) and recommendations for improved reporting were given. In study two findings suggested that significant barriers to scale-up existed including lack of management support and time and cost of the intervention. Results from study three suggest that improvements could be made across the RE-AIM framework to facilitate improved effectiveness of the application while maintaining and improving reach, adoption, implementation and maintenance. Conclusion: The studies presented in this thesis will inform and improve the dissemination and implementation of SB interventions in the workplace for impact in the real world. Future research in this area should look to: implement testing for potential public health impact in early phases of research; further investigate the resources for health promotion in the real world and the stakeholder's perceptions of costs and benefits of interventions; investigate the manager's role as a gatekeeper to behaviour change in the workplace
Re-evaluation of the in vitro activity of the protease activated receptor-1 (PAR1) pepducin PZ-128
No full textMyocardial infarction and stroke are some of the leading causes of death globally, with antiplatelet agents commonly used for the clinical management of these conditions. Unfortunately, not all patients respond to existing antiplatelet therapies, which can result in vascular event recurrence and death. This has led to the need to develop alternative ways to inhibit platelet activity and prevent thrombus formation. Protease-activated receptor 1 (PAR1) is a key target due to its role in thrombin-mediated platelet activation.;PZ-128 is a cell penetrable pepducin that targets PAR1 and has entered phase II clinical trials, however, adverse effects in trial subjects have emerged that warrant reappraisal of its basic pharmacology. The aim of this thesis was to re-evaluate PZ-128 pharmacology using in vitro models to assess cellular toxicity and confirm if PZ-128 possesses the ability to promote cellular activity beyond its existing role as a PAR1 inhibitor. The methodology used for this purpose included the study of intracellular Ca2+ mobilisation, cell viability assessment, pAkt and pERK quantification, and receptor localisation studies.;TsA201 and HEK293 cells were used as they express endogenous levels of PAR1 and can be transfected with PAR1 tagged plasmids. Studies with PZ-128 (palmitate-KKSRALF-NH2) were carried out in parallel with a control pepducin (Sc-128) which is comprised of the same amino acids as PZ-128 which have been rearranged in sequence (palmitate-FSRLKAK-NH2). Treatment with thrombin (EC50 0.577 U/mL) or the synthetic PAR1 agonist TFLLR-NH2 (EC50 8.89 μM) confirmed PAR1 expression and receptor activity using Fluo-4 AM calcium flux assays. MTT assay was used to assess cell viability, with significant cell death observed in PZ-128-treated cells following 100 μM exposure for 24 hours, which coincided with loss of pAkt.;Interestingly, PZ-128 (25-100 μM), but not Sc-128, induced a dose-dependent increase in intracellular Ca2+ levels that was sustained and distinct from thrombin and TFLLR-NH2 responses. PZ-128 (30 μM) also caused sustained ERK phosphorylation (15-60 min). As GPCR internalisation events are common after receptor activation, the ability of PZ-128 to impact PAR1 localisation was assessed. Thrombin (1 U/mL for 30 minutes) efficiently internalised PAR1-GFP in transfected cells, however, no internalisation was observed in response to Sc-128 or PZ-128.;These results suggest that PZ-128 possesses activity that may compromise the cytosolic Ca2+ homeostasis and promote proliferative activity through activation of ERK MAPK pathways. Re-evaluation of existing published pharmacology of PZ-128 is needed to truly understand its full biological activity.;Cyclic analogues of PZ-128 have since been developed in collaboration with the Liskamp laboratory with the aim of advancing pepducin-based targeting of PAR1. While initial pilot studies were started in this thesis (HL-07 and HL-10), full characterisation was out with the scope of this project and is currently ongoing. Improvements to the design of PZ-128 may limit the cellular activity observed and will form the basis of future development.Myocardial infarction and stroke are some of the leading causes of death globally, with antiplatelet agents commonly used for the clinical management of these conditions. Unfortunately, not all patients respond to existing antiplatelet therapies, which can result in vascular event recurrence and death. This has led to the need to develop alternative ways to inhibit platelet activity and prevent thrombus formation. Protease-activated receptor 1 (PAR1) is a key target due to its role in thrombin-mediated platelet activation.;PZ-128 is a cell penetrable pepducin that targets PAR1 and has entered phase II clinical trials, however, adverse effects in trial subjects have emerged that warrant reappraisal of its basic pharmacology. The aim of this thesis was to re-evaluate PZ-128 pharmacology using in vitro models to assess cellular toxicity and confirm if PZ-128 possesses the ability to promote cellular activity beyond its existing role as a PAR1 inhibitor. The methodology used for this purpose included the study of intracellular Ca2+ mobilisation, cell viability assessment, pAkt and pERK quantification, and receptor localisation studies.;TsA201 and HEK293 cells were used as they express endogenous levels of PAR1 and can be transfected with PAR1 tagged plasmids. Studies with PZ-128 (palmitate-KKSRALF-NH2) were carried out in parallel with a control pepducin (Sc-128) which is comprised of the same amino acids as PZ-128 which have been rearranged in sequence (palmitate-FSRLKAK-NH2). Treatment with thrombin (EC50 0.577 U/mL) or the synthetic PAR1 agonist TFLLR-NH2 (EC50 8.89 μM) confirmed PAR1 expression and receptor activity using Fluo-4 AM calcium flux assays. MTT assay was used to assess cell viability, with significant cell death observed in PZ-128-treated cells following 100 μM exposure for 24 hours, which coincided with loss of pAkt.;Interestingly, PZ-128 (25-100 μM), but not Sc-128, induced a dose-dependent increase in intracellular Ca2+ levels that was sustained and distinct from thrombin and TFLLR-NH2 responses. PZ-128 (30 μM) also caused sustained ERK phosphorylation (15-60 min). As GPCR internalisation events are common after receptor activation, the ability of PZ-128 to impact PAR1 localisation was assessed. Thrombin (1 U/mL for 30 minutes) efficiently internalised PAR1-GFP in transfected cells, however, no internalisation was observed in response to Sc-128 or PZ-128.;These results suggest that PZ-128 possesses activity that may compromise the cytosolic Ca2+ homeostasis and promote proliferative activity through activation of ERK MAPK pathways. Re-evaluation of existing published pharmacology of PZ-128 is needed to truly understand its full biological activity.;Cyclic analogues of PZ-128 have since been developed in collaboration with the Liskamp laboratory with the aim of advancing pepducin-based targeting of PAR1. While initial pilot studies were started in this thesis (HL-07 and HL-10), full characterisation was out with the scope of this project and is currently ongoing. Improvements to the design of PZ-128 may limit the cellular activity observed and will form the basis of future development
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