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Recovery and remediation potential of copper and other PTEs in tailings from the Zambian copperbelt
Full text linkMining activities generate large amounts of waste that can be detrimental to human health
and the environment. In Zambia, mining has been ongoing since 1920 and potentially toxic
elements (PTEs) have been left in mine wastes including copper mine tailings. Tailings of the Copperbelt including the bottom soil where they are currently sitting contain high enough levels of copper that they can be regarded as ore in other regions. This research focuses on recovery and remediation of copper and other PTEs in some tailings of the Copperbelt Province. Tailings were collected from three tailings sites in the Zambian Copperbelt: Akatiti, Kitwe, and Uchi. These tailings were thought to be from different time periods of mining with Akatiti coming from the second-oldest tailings dam in Zambia and Kitwe and Uchi coming from more recent activities. Physical and chemical characterisation of the tailings were carried out. All tailings and underlying soil material were classified as coarse-grained sands with some gravel and silt present at times. All were neutral to mildly alkaline (7.2≤pH ≤8.5). Copper content in tailings varied from 0.2-0.8% by mass, comparable to ore in other regions, and cobalt contents varied from 0.008-0.05% by mass. Underlying soils had copper and cobalt contents of 0.07-0.8% and 0.008-0.05%, respectively, indicating some mobilisation had likely occurred already. These levels indicated both opportunity for copper and cobalt recovery and need for remediation. Copper recovery from mined materials is normally carried out by pyrometallurgical or hydrometallurgical processes. Analogous to these methods, thermal treatments and soil washing were explored for potential copper-cobalt recovery and remediation in Akatiti and Uchi tailings. Thermal treatments involved smouldering or roasting. Treating the tailings via smouldering made the PTEs become more immobile and resistant to leaching, including copper. Roasting at 600°C and 1000°C had similar effects to differing extents. Smouldering and roasting affected the mineralogy of the tailings, changing the native pH and availability of PTEs including copper to differing extents. In contrast, soil washing with 0.5 M hydrochloric acid for 24 hours recovered 94%, 100%, and 58% of copper from Akatiti, Kitwe, and Uchi tailings, respectively, while also recovering 7-45% of other PTEs. This work shows that a combined remediation and resource recovery approach is feasible for Zambia’s copper tailings and should be explored to contribute to the 2030 national vision of Zambia for creating jobs for the local communities.Mining activities generate large amounts of waste that can be detrimental to human health
and the environment. In Zambia, mining has been ongoing since 1920 and potentially toxic
elements (PTEs) have been left in mine wastes including copper mine tailings. Tailings of the Copperbelt including the bottom soil where they are currently sitting contain high enough levels of copper that they can be regarded as ore in other regions. This research focuses on recovery and remediation of copper and other PTEs in some tailings of the Copperbelt Province. Tailings were collected from three tailings sites in the Zambian Copperbelt: Akatiti, Kitwe, and Uchi. These tailings were thought to be from different time periods of mining with Akatiti coming from the second-oldest tailings dam in Zambia and Kitwe and Uchi coming from more recent activities. Physical and chemical characterisation of the tailings were carried out. All tailings and underlying soil material were classified as coarse-grained sands with some gravel and silt present at times. All were neutral to mildly alkaline (7.2≤pH ≤8.5). Copper content in tailings varied from 0.2-0.8% by mass, comparable to ore in other regions, and cobalt contents varied from 0.008-0.05% by mass. Underlying soils had copper and cobalt contents of 0.07-0.8% and 0.008-0.05%, respectively, indicating some mobilisation had likely occurred already. These levels indicated both opportunity for copper and cobalt recovery and need for remediation. Copper recovery from mined materials is normally carried out by pyrometallurgical or hydrometallurgical processes. Analogous to these methods, thermal treatments and soil washing were explored for potential copper-cobalt recovery and remediation in Akatiti and Uchi tailings. Thermal treatments involved smouldering or roasting. Treating the tailings via smouldering made the PTEs become more immobile and resistant to leaching, including copper. Roasting at 600°C and 1000°C had similar effects to differing extents. Smouldering and roasting affected the mineralogy of the tailings, changing the native pH and availability of PTEs including copper to differing extents. In contrast, soil washing with 0.5 M hydrochloric acid for 24 hours recovered 94%, 100%, and 58% of copper from Akatiti, Kitwe, and Uchi tailings, respectively, while also recovering 7-45% of other PTEs. This work shows that a combined remediation and resource recovery approach is feasible for Zambia’s copper tailings and should be explored to contribute to the 2030 national vision of Zambia for creating jobs for the local communities
Supramolecular chemistry for the application to hair dye technology
Full text linkThis thesis investigates the use of co-crystallisation and crystal engineering to create novel coloured co-crystalline materials (i.e. co-crystals or salts) which can be used to colour hair. Based on the limited previous work on supramolecular hair dyes, we attempted to increase the range of available colours. Firstly, the solution reactivity of p-phenylenediamine (PPD) was investigated through the use of UV/Vis, HPLC, LC-MS and NMR spectroscopy which was monitored over three months. The colour of the PPD solutions was observed to change from colourless to a deep red/black during this time which suggested that oxidation was possibly occurring which was confirmed through the use of HPLC, LC-MS and NMR. These techniques, particularly LC-MS allowed us to identify the nature of these oxidation products. Secondly, the effect small structural changes to PPD would have on the resultant colour was investigated using o-phenylenediamine (OPD), m-phenylenediamine (MPD) and 4 iodoaniline (4IODAN). The results showed small shifts by UV/Vis occurring over time which from the PPD work in the previous chapter was more likely a result of oxidation. The impact of ionisation was also investigated through ionic co-crystals of PPD which were unsuccessful, although formation of the HCl salt did result in a colour change in the solution state. Lastly, alizarin was screened for new multi-component forms that could extend the range of available colours. A new pyridine solvate as well as three new co-crystals were identified through solution crystallisation and ball milling experiments. An additional ALZ-PHN co crystal was identified through liquid-assisted grinding (LAG) experiments which was isostructural to the ACR co-crystal. UV/Vis analysis of these new crystalline materials identified did not show any shift in colour with respect to ALZ and as a result did not offer any advantage over pure ALZ.This thesis investigates the use of co-crystallisation and crystal engineering to create novel coloured co-crystalline materials (i.e. co-crystals or salts) which can be used to colour hair. Based on the limited previous work on supramolecular hair dyes, we attempted to increase the range of available colours. Firstly, the solution reactivity of p-phenylenediamine (PPD) was investigated through the use of UV/Vis, HPLC, LC-MS and NMR spectroscopy which was monitored over three months. The colour of the PPD solutions was observed to change from colourless to a deep red/black during this time which suggested that oxidation was possibly occurring which was confirmed through the use of HPLC, LC-MS and NMR. These techniques, particularly LC-MS allowed us to identify the nature of these oxidation products. Secondly, the effect small structural changes to PPD would have on the resultant colour was investigated using o-phenylenediamine (OPD), m-phenylenediamine (MPD) and 4 iodoaniline (4IODAN). The results showed small shifts by UV/Vis occurring over time which from the PPD work in the previous chapter was more likely a result of oxidation. The impact of ionisation was also investigated through ionic co-crystals of PPD which were unsuccessful, although formation of the HCl salt did result in a colour change in the solution state. Lastly, alizarin was screened for new multi-component forms that could extend the range of available colours. A new pyridine solvate as well as three new co-crystals were identified through solution crystallisation and ball milling experiments. An additional ALZ-PHN co crystal was identified through liquid-assisted grinding (LAG) experiments which was isostructural to the ACR co-crystal. UV/Vis analysis of these new crystalline materials identified did not show any shift in colour with respect to ALZ and as a result did not offer any advantage over pure ALZ
Coaxial extrusion of fine diameter tissue filaments
Full text linkCoaxial extrusion is a promising technology, which employs a coaxial nozzle composed of two concentrically aligned nozzles (an inner core nozzle and an outer shell nozzle) to fabricate transplantable and autologous tissue filaments contained within robust, porous hydrogel scaffolds. These extruded scaffolds are capable of restoring function to various fibrous tissues within the body, such as peripheral nerve and muscle, which have lost the ability to naturally regenerate through irreversible disease or trauma.The overall aim of this work was to develop a coaxial bio-extrusion platform to create fine diameter extruded stem cell-laden tissue filaments with the capability to retain long-term viability in culture. Further objectives were to develop a hydrogel scaffold material capable of resisting degradation by culture media to maintain tissue filament integrity. It was also desirable to demonstrate extrusion with multiple cell types and to present an initial assessment of the viability of the coaxial extrusion platform for use in drug testing applications, providing the benefit of a more natural in vivo-like environment to study drug-cell interactions in comparison to traditional two-dimensional methods.By embedding cells within an extracellular matrix material, such as collagen, an extrudable bioink is created, which may be placed within the inner core of a concentrically aligned coaxial nozzle. By simultaneously extruding using alginate within the outer shell nozzle into a crosslinking bath containing divalent cations such as Ca2+, hollow tubular alginate scaffolds containing cell-laden collagen filaments may be produced. By manipulating key extrusion parameters such as flow rate magnitude, core/shell flow rate and collagen concentration, filament diameters were successfully reduced from > 400 μm to sub-20 μm, consequently aiding nutrient diffusion and long-term cell survival in culture.Small diameter (sub-20 μm) adipose-derived stem cell-laden collagen filaments have been extruded and matured with high viability (> 90%) over a 21-day period, achieved by modification of the core/shell flow rate ratio and collagen concentration. Combined calcium and barium cross-linking was employed in order to maintain scaffold integrity by tuning alginate cross-linking concentration, time and ion type. The coaxial extrusion platform was also used to extrude and culture human hepatoma HepaRG cells within small diameter filaments (sub-25 μm), which sustained viability for 14 days, thus demonstrating extrusion using multiple cell types. The preliminary viability of the coaxial extruder to be utilised in drug testing applications has been assessed by performing hepatotoxicity tests of HepaRG cells and obtaining LC50 values similar to published data for three compounds. An additional assay of CYP450 enzyme activity further validated this platform by demonstrating strong CYP3A4 activity on induction with rifampicin, a known CYP3A4 inducer.To conclude, a coaxial extrusion platform was created, wherein fine diameter (sub-20 μm) collagen filaments containing adipose-derived stem cells were fabricated and cultured, retaining high viability (> 90%) over multiple days (> 21 days). This achievement was aided by the tuning of material flow rates, alginate shell cross-linking parameters and collagen concentration. Finally, fine diameter collagen filaments containing human hepatoma HepaRG cells (sub-25 μm) were also extruded and cultured at high viability for 14 days. These HepaRG-containing filaments were also exposed to different hepatotoxic compounds at varying concentrations to obtain LC50 values comparable to literature, thus providing preliminary validation of the coaxial extrusion system to be used as a drug testing platform.Coaxial extrusion is a promising technology, which employs a coaxial nozzle composed of two concentrically aligned nozzles (an inner core nozzle and an outer shell nozzle) to fabricate transplantable and autologous tissue filaments contained within robust, porous hydrogel scaffolds. These extruded scaffolds are capable of restoring function to various fibrous tissues within the body, such as peripheral nerve and muscle, which have lost the ability to naturally regenerate through irreversible disease or trauma.The overall aim of this work was to develop a coaxial bio-extrusion platform to create fine diameter extruded stem cell-laden tissue filaments with the capability to retain long-term viability in culture. Further objectives were to develop a hydrogel scaffold material capable of resisting degradation by culture media to maintain tissue filament integrity. It was also desirable to demonstrate extrusion with multiple cell types and to present an initial assessment of the viability of the coaxial extrusion platform for use in drug testing applications, providing the benefit of a more natural in vivo-like environment to study drug-cell interactions in comparison to traditional two-dimensional methods.By embedding cells within an extracellular matrix material, such as collagen, an extrudable bioink is created, which may be placed within the inner core of a concentrically aligned coaxial nozzle. By simultaneously extruding using alginate within the outer shell nozzle into a crosslinking bath containing divalent cations such as Ca2+, hollow tubular alginate scaffolds containing cell-laden collagen filaments may be produced. By manipulating key extrusion parameters such as flow rate magnitude, core/shell flow rate and collagen concentration, filament diameters were successfully reduced from > 400 μm to sub-20 μm, consequently aiding nutrient diffusion and long-term cell survival in culture.Small diameter (sub-20 μm) adipose-derived stem cell-laden collagen filaments have been extruded and matured with high viability (> 90%) over a 21-day period, achieved by modification of the core/shell flow rate ratio and collagen concentration. Combined calcium and barium cross-linking was employed in order to maintain scaffold integrity by tuning alginate cross-linking concentration, time and ion type. The coaxial extrusion platform was also used to extrude and culture human hepatoma HepaRG cells within small diameter filaments (sub-25 μm), which sustained viability for 14 days, thus demonstrating extrusion using multiple cell types. The preliminary viability of the coaxial extruder to be utilised in drug testing applications has been assessed by performing hepatotoxicity tests of HepaRG cells and obtaining LC50 values similar to published data for three compounds. An additional assay of CYP450 enzyme activity further validated this platform by demonstrating strong CYP3A4 activity on induction with rifampicin, a known CYP3A4 inducer.To conclude, a coaxial extrusion platform was created, wherein fine diameter (sub-20 μm) collagen filaments containing adipose-derived stem cells were fabricated and cultured, retaining high viability (> 90%) over multiple days (> 21 days). This achievement was aided by the tuning of material flow rates, alginate shell cross-linking parameters and collagen concentration. Finally, fine diameter collagen filaments containing human hepatoma HepaRG cells (sub-25 μm) were also extruded and cultured at high viability for 14 days. These HepaRG-containing filaments were also exposed to different hepatotoxic compounds at varying concentrations to obtain LC50 values comparable to literature, thus providing preliminary validation of the coaxial extrusion system to be used as a drug testing platform
An exploration of how teachers in Scotland enact professional standards and the influence of teacher professionalism
Full text linkThere is a plethora of literature that discusses Professional Standards, however, there is a lack of empirical research about the impact of the enactment of Professional Standards. The aim of this research is to add to this literature, as it investigates how teachers in Scotland enact Professional Standards as policy. In this research, I adopted a multi-perspective research approach (Kincheloe, 2011) and adapted and combined theoretical frameworks, rather than accepting a pre-existing framework that did not fully fit with my research. This involved critical analysis of policy and Positioning Theory, drawing on the work of Adams (2011, 2016), Bamberg (2014) and Davies & Harré, (1990), interrogating literature on Professional Standards and teacher professionalism through Evetts (2013) lens of organisational and occupational professionalism and using Ball’s (1994, 1997, 2008) Theory of Enactment. This was supported through data collection from semi-structured interviews to gather the voices of Scottish teachers about their enactment of Professional Standards. Professional Standards promote a particular view of teachers, teaching and teacher professionalism. Their multiple purposes are not widely acknowledged, and the policy discourse offers various positions within the macro, meso, micro and nano levels of policy enactment. Teacher professionalism, school leaders and context have an important role toplay in determining how, or whether teachers enact Professional Standards. I have offered a new contribution to knowledge about the enactment of policy, which considers policy discourse and the influence of Positioning Theory, and teacher professionalism to show how this creates a multitude of outcomes in practice. Finally, I suggest further research that would be insightful to support further knowledge development about the enactment of policy and Professional Standards.There is a plethora of literature that discusses Professional Standards, however, there is a lack of empirical research about the impact of the enactment of Professional Standards. The aim of this research is to add to this literature, as it investigates how teachers in Scotland enact Professional Standards as policy. In this research, I adopted a multi-perspective research approach (Kincheloe, 2011) and adapted and combined theoretical frameworks, rather than accepting a pre-existing framework that did not fully fit with my research. This involved critical analysis of policy and Positioning Theory, drawing on the work of Adams (2011, 2016), Bamberg (2014) and Davies & Harré, (1990), interrogating literature on Professional Standards and teacher professionalism through Evetts (2013) lens of organisational and occupational professionalism and using Ball’s (1994, 1997, 2008) Theory of Enactment. This was supported through data collection from semi-structured interviews to gather the voices of Scottish teachers about their enactment of Professional Standards. Professional Standards promote a particular view of teachers, teaching and teacher professionalism. Their multiple purposes are not widely acknowledged, and the policy discourse offers various positions within the macro, meso, micro and nano levels of policy enactment. Teacher professionalism, school leaders and context have an important role toplay in determining how, or whether teachers enact Professional Standards. I have offered a new contribution to knowledge about the enactment of policy, which considers policy discourse and the influence of Positioning Theory, and teacher professionalism to show how this creates a multitude of outcomes in practice. Finally, I suggest further research that would be insightful to support further knowledge development about the enactment of policy and Professional Standards
Understanding and mitigating agglomeration and attrition during the drying of Paracetamol
Full text linkOral dose formulation is quite common for most commercial pharmaceutical products. The performance of a drug product is mainly dependent on the physical properties of the active pharmaceutical ingredient (API). As such, great care is taken during the production of the API to achieve a target particle size distribution. Control of the API particle‐size distribution is traditionally achieved via the crystallization process. A significant amount of effort goes into designing crystallization processes that consistently produce the desired API properties on scale‐up. The isolation (filtration, washing, and drying) process is needed to separate the pure product crystals from the impure mother liquor to produce dry, free-flowing particles while preserving the particle size distribution achieved by crystallization. Drying is the last and critical processing step in the isolation and purification of API crystals which is performed to remove the residual solvent remaining after filtration and washing. The effectiveness of the drying process affects the quality attributes of the final drug product. Traces of residual solvent may also affect the stability of the formulated product. Any API dissolved in the residual solvent left during drying tends to create "sticky" points at the contacts between particles, promoting solid bridges and being responsible for particle agglomeration. The residual moisture content and composition, solvent polarity, surface tension, and viscosity significantly impact agglomeration. The drying process can also impact the particle‐size distribution of the API, which affects the stability, bioavailability, dissolution rate and content uniformity of the drug product and the reproducibility of the manufacturing process. The main aim of this work was to explore the role of residual solvent during drying by quantifying the threshold limit of the residual moisture content and the dissolved material to form a robust agglomerate. Based on using a model API, paracetamol, the results indicating the minimum API mass that can cause agglomeration is helpful information to support the design of filter cake-washing processes to avoid agglomeration. This research also addresses the work done for developing a convenient method for quantifying agglomerate brittleness based on experimental validation. Further objectives include the work done to analyze the interaction and transport of residual solvent with API during drying by evaluating the role of contact angles and capillary forces to understand the transport of residual moisture and the dissolved material during drying. The final component was the development of a semi-empirical approach based on the correlation of material properties and breakage assessment tests to provide a corresponding scale-down concept/apparatus for mimicking particle breakage in agitated dryers at various scales.Oral dose formulation is quite common for most commercial pharmaceutical products. The performance of a drug product is mainly dependent on the physical properties of the active pharmaceutical ingredient (API). As such, great care is taken during the production of the API to achieve a target particle size distribution. Control of the API particle‐size distribution is traditionally achieved via the crystallization process. A significant amount of effort goes into designing crystallization processes that consistently produce the desired API properties on scale‐up. The isolation (filtration, washing, and drying) process is needed to separate the pure product crystals from the impure mother liquor to produce dry, free-flowing particles while preserving the particle size distribution achieved by crystallization. Drying is the last and critical processing step in the isolation and purification of API crystals which is performed to remove the residual solvent remaining after filtration and washing. The effectiveness of the drying process affects the quality attributes of the final drug product. Traces of residual solvent may also affect the stability of the formulated product. Any API dissolved in the residual solvent left during drying tends to create "sticky" points at the contacts between particles, promoting solid bridges and being responsible for particle agglomeration. The residual moisture content and composition, solvent polarity, surface tension, and viscosity significantly impact agglomeration. The drying process can also impact the particle‐size distribution of the API, which affects the stability, bioavailability, dissolution rate and content uniformity of the drug product and the reproducibility of the manufacturing process. The main aim of this work was to explore the role of residual solvent during drying by quantifying the threshold limit of the residual moisture content and the dissolved material to form a robust agglomerate. Based on using a model API, paracetamol, the results indicating the minimum API mass that can cause agglomeration is helpful information to support the design of filter cake-washing processes to avoid agglomeration. This research also addresses the work done for developing a convenient method for quantifying agglomerate brittleness based on experimental validation. Further objectives include the work done to analyze the interaction and transport of residual solvent with API during drying by evaluating the role of contact angles and capillary forces to understand the transport of residual moisture and the dissolved material during drying. The final component was the development of a semi-empirical approach based on the correlation of material properties and breakage assessment tests to provide a corresponding scale-down concept/apparatus for mimicking particle breakage in agitated dryers at various scales
Local political leadership and administrative capacity for EU Structural Funds : the case of Cohesion policy in urban Romania
Full text linkPrimary supervisor: John BachtlerThe EU Structural Funds are instruments to support less developed regions, aiming to close the gap between Europe's least and most developed regions. Their implementation is essential for the EU's regional policy to achieve economic development. Empirical evidence indicates that the implementation rate of Structural Funds in Romania has been consistently low. However, at regional and local levels, a different pattern emerges. This thesis emphasises the critical roles of local political leadership and administrative capacity to explain the success of local authorities in securing EU resources in a context unfavourable to such an outcome. Through an empirical analysis of thirteen municipalities during the 2014- 2020 programming cycle, this study assesses the ability of local elected leaders to leverage EU funds to address local needs and evaluates the administrative capacity in each municipality. It finds that political leaders affect implementation through the strategic decisions and actions they take in the early stages of the process (formulation), through the measures they undertake to mobilize resources and enable the public administrations to attract funds (mobilization) and the assistance offered during implementation. While administrative capacity is an essential and necessary condition for attracting resources, it remains insufficient without political drive. The findings confirm the intertwined nature of politics and administration in the implementation of EU Structural Funds, highlighting the significant role political leaders play alongside administrative capacity.The EU Structural Funds are instruments to support less developed regions, aiming to close the gap between Europe's least and most developed regions. Their implementation is essential for the EU's regional policy to achieve economic development. Empirical evidence indicates that the implementation rate of Structural Funds in Romania has been consistently low. However, at regional and local levels, a different pattern emerges. This thesis emphasises the critical roles of local political leadership and administrative capacity to explain the success of local authorities in securing EU resources in a context unfavourable to such an outcome. Through an empirical analysis of thirteen municipalities during the 2014- 2020 programming cycle, this study assesses the ability of local elected leaders to leverage EU funds to address local needs and evaluates the administrative capacity in each municipality. It finds that political leaders affect implementation through the strategic decisions and actions they take in the early stages of the process (formulation), through the measures they undertake to mobilize resources and enable the public administrations to attract funds (mobilization) and the assistance offered during implementation. While administrative capacity is an essential and necessary condition for attracting resources, it remains insufficient without political drive. The findings confirm the intertwined nature of politics and administration in the implementation of EU Structural Funds, highlighting the significant role political leaders play alongside administrative capacity
Investigating the effects of metal-on-metal hip implants and circulating cobalt ions on cardiovascular function
Full text linkMetal-on-metal (MoM) hip arthroplasties are known to release metal ions including cobalt into the blood stream. Elevated blood cobalt at levels over 250µg/l have been shown to be a risk factor for developing cardiovascular complications including cardiomyopathy, a need for cardiac transplantation and, in some cases, death. Published case reports document cardiomyopathy in patients with elevated blood cobalt levels below 250µg/l and as low as 13µg/l. Clinical studies have found conflicting evidence of cobalt-induced cardiomyopathy in patients with MoM hips. Global longitudinal strain (GLS) is an echocardiography measurement known to be more sensitive than ejection fraction at diagnosing early cardiomyopathies. The extent of cardiovascular injury, as measured by GLS, in patients withelevated blood cobalt levels has not previously been examined and is the focus of the current study. Sixteen patients with documented blood cobalt ion levels above 13µg/l were identified from a regional arthroplasty database. They were age and sex matched with eight patients awaiting hip arthroplasty with no history of cobalt implants. All patients underwent electrocardiogram and echocardiogram assessment for signs of cardiomyopathy includingleft ventricular (LV) dysfunction and cardiac remodelling. Global longitudinal strain (GLS), E/e’ ratio (an index for evaluating LV filling pressure), ejection fraction, LV wall thickness, LV end diastolic dimension, LV end systolic dimension and fractional shortening were all assessed. The patients with MoM hip arthroplasties had a mean time from initial arthroplasty of 15 years and had a mean blood cobalt level of 29µg/l compared to 0.01µg/l in the control group. Echocardiographic analysis showed no difference in either LV end systolic dimension (2.8cm v 3.0cm, (MoM v control) p=0.592) or LV end diastolic dimension (4.7cm v 5.0cm, (MoM v control) p=0.259). Neither was there any difference between ejection fraction (61.5% v 63.7%, (MoM v control) p= 0.564) or fractional shortening (38.9% v 40.1%, (MoM v control) p=0.813). Ventricular wall thickness (1.2cm v 1.0cm, p=0.059) and E/e’ ratio (8.0 v 7.8, p=0.771) were also comparable across MoM and control groups and there was no difference in rates of left ventricular or atrial hypertrophy. GLS was significantly reduced in patients with MoM hip arthroplasties compared to those without (-15.2% v -18%, (MoM v control) p= 0.013).This study has demonstrated reduced cardiac function in the presence of normal ejection fraction as assessed by GLS in patients with elevated cobalt above 13µg/l. As GLS is a more sensitive measure of systolic function than ejection fraction, routine echocardiogram assessment including GLS should be performed in all patients with MoM hip arthroplasties and elevated blood cobalt above 13µg/l. Further work is recommended to assess if thesecardiac changes are present in patients with elevated blood cobalt levels below 13µg/l.Metal-on-metal (MoM) hip arthroplasties are known to release metal ions including cobalt into the blood stream. Elevated blood cobalt at levels over 250µg/l have been shown to be a risk factor for developing cardiovascular complications including cardiomyopathy, a need for cardiac transplantation and, in some cases, death. Published case reports document cardiomyopathy in patients with elevated blood cobalt levels below 250µg/l and as low as 13µg/l. Clinical studies have found conflicting evidence of cobalt-induced cardiomyopathy in patients with MoM hips. Global longitudinal strain (GLS) is an echocardiography measurement known to be more sensitive than ejection fraction at diagnosing early cardiomyopathies. The extent of cardiovascular injury, as measured by GLS, in patients withelevated blood cobalt levels has not previously been examined and is the focus of the current study. Sixteen patients with documented blood cobalt ion levels above 13µg/l were identified from a regional arthroplasty database. They were age and sex matched with eight patients awaiting hip arthroplasty with no history of cobalt implants. All patients underwent electrocardiogram and echocardiogram assessment for signs of cardiomyopathy includingleft ventricular (LV) dysfunction and cardiac remodelling. Global longitudinal strain (GLS), E/e’ ratio (an index for evaluating LV filling pressure), ejection fraction, LV wall thickness, LV end diastolic dimension, LV end systolic dimension and fractional shortening were all assessed. The patients with MoM hip arthroplasties had a mean time from initial arthroplasty of 15 years and had a mean blood cobalt level of 29µg/l compared to 0.01µg/l in the control group. Echocardiographic analysis showed no difference in either LV end systolic dimension (2.8cm v 3.0cm, (MoM v control) p=0.592) or LV end diastolic dimension (4.7cm v 5.0cm, (MoM v control) p=0.259). Neither was there any difference between ejection fraction (61.5% v 63.7%, (MoM v control) p= 0.564) or fractional shortening (38.9% v 40.1%, (MoM v control) p=0.813). Ventricular wall thickness (1.2cm v 1.0cm, p=0.059) and E/e’ ratio (8.0 v 7.8, p=0.771) were also comparable across MoM and control groups and there was no difference in rates of left ventricular or atrial hypertrophy. GLS was significantly reduced in patients with MoM hip arthroplasties compared to those without (-15.2% v -18%, (MoM v control) p= 0.013).This study has demonstrated reduced cardiac function in the presence of normal ejection fraction as assessed by GLS in patients with elevated cobalt above 13µg/l. As GLS is a more sensitive measure of systolic function than ejection fraction, routine echocardiogram assessment including GLS should be performed in all patients with MoM hip arthroplasties and elevated blood cobalt above 13µg/l. Further work is recommended to assess if thesecardiac changes are present in patients with elevated blood cobalt levels below 13µg/l
Designing effective interface configurations in touchscreen eyes-free interaction
Full text linkSmartphones are considered ubiquitous in our daily life, allowing us to conveniently manipulate data while simultaneously performing other tasks. Unfortunately, our interaction with smartphone interfaces can act as a distraction from other activities which could put the user at risk. Without unique tactile cues on the touchscreen, the users are forced to devote moreattention to carrying out their task at hand. Interface design for eyes-free interaction with a featureless screen is therefore a highly challenging, and informative approach. By simplifying and optimising menu layout patterns and understanding how to locate and memorise active touchpoints, there is an opportunity to create touchscreen interfaces that harness innate humanabilities and product affordances, allowing the reduction of levels of visual attention. Therefore, this research aims to enhance understanding of human cognitive abilities that are proprioception and spatial memory to deliver a framework and guidelines that help support effective eyes-free interface configurations of touchscreen surfaces. The configuration of interface elements in relation to thumb motion under the mobile screen frame and human spatial memory become key aspects to be considered in designing an eyes-free interface for one-handed mobile interaction. The interface prototypes were developed to test for certain qualities of design. Two experiments are conducted to test the performance accuracy of interfaces caused by spatial memory and proprioception. Participants need to memorise the visual interface which has been viewed before imagining a relative spatial layout and tap on a match position of the target with tactile sense on the unseen flat mobile screen. Insight from the experimental findings brought about the development of the design framework suggesting key interface configuration characteristics to synergise the strengths of spatial memory and proprioception. These include horizontal alignment, structure with even button spacing, unified layout, middle segmentation, symmetry in a square, and proximity to the device frame within a comfortable thumb range. Following the development of this novelconceptual framework, design guidelines were then developed to support the practitioner to configure the eyes-free interfaces to attain high accuracy and efficiency. In the practical study, three novel application layouts were proposed and evaluated. In addition, interviews with experienced user interface designers were conducted for insights into the suitability of the design framework and design guidelines. The fundamentals in this thesis have the potential to be used in designing touchscreen layouts allowing better interaction with smartphones with a low level of visual attention. This thesis demonstrates a contribution to knowledge through the development and application of eyes-free interface prototypes.Smartphones are considered ubiquitous in our daily life, allowing us to conveniently manipulate data while simultaneously performing other tasks. Unfortunately, our interaction with smartphone interfaces can act as a distraction from other activities which could put the user at risk. Without unique tactile cues on the touchscreen, the users are forced to devote moreattention to carrying out their task at hand. Interface design for eyes-free interaction with a featureless screen is therefore a highly challenging, and informative approach. By simplifying and optimising menu layout patterns and understanding how to locate and memorise active touchpoints, there is an opportunity to create touchscreen interfaces that harness innate humanabilities and product affordances, allowing the reduction of levels of visual attention. Therefore, this research aims to enhance understanding of human cognitive abilities that are proprioception and spatial memory to deliver a framework and guidelines that help support effective eyes-free interface configurations of touchscreen surfaces. The configuration of interface elements in relation to thumb motion under the mobile screen frame and human spatial memory become key aspects to be considered in designing an eyes-free interface for one-handed mobile interaction. The interface prototypes were developed to test for certain qualities of design. Two experiments are conducted to test the performance accuracy of interfaces caused by spatial memory and proprioception. Participants need to memorise the visual interface which has been viewed before imagining a relative spatial layout and tap on a match position of the target with tactile sense on the unseen flat mobile screen. Insight from the experimental findings brought about the development of the design framework suggesting key interface configuration characteristics to synergise the strengths of spatial memory and proprioception. These include horizontal alignment, structure with even button spacing, unified layout, middle segmentation, symmetry in a square, and proximity to the device frame within a comfortable thumb range. Following the development of this novelconceptual framework, design guidelines were then developed to support the practitioner to configure the eyes-free interfaces to attain high accuracy and efficiency. In the practical study, three novel application layouts were proposed and evaluated. In addition, interviews with experienced user interface designers were conducted for insights into the suitability of the design framework and design guidelines. The fundamentals in this thesis have the potential to be used in designing touchscreen layouts allowing better interaction with smartphones with a low level of visual attention. This thesis demonstrates a contribution to knowledge through the development and application of eyes-free interface prototypes
The role of microbiome in mast cells mediated induction of protective and pathological responses
No full textHelminth infections predominantly occur in countries with inadequate environmental sanitation. Around 1.5 million people are infected with different helminth species including hookworms, roundworms, and whipworms. Roundworms are commonly isolated in human, and in particular a zoonotic nematode, T. spiralis is crucially important as it infects humans through food chain by consumption of undercooked meat such as pork, or game meat causing diseases which lead to an increased burdens in economy especially medical, educational costs. The need to find suitable, accurate and cost-effective diagnostic approaches, as well as the way to strengthening natural protective and pathological immune responses driven by MCs against T. spiralis is fundamental to pave that way to control and minimizing the risk of infections. Study of the effect of gut microbiome on immune responses is at its early stage, and only few studies have suggested that the presence of microbiome can affect immune responses. In this study we firstly evaluated the effect of microbiome on helminth induced protective and pathological immune responses driven by mast cells during T. spiralis infection. Secondly, we analysed the specificity and relevance of ELISA in the detection of T. spiralis infection, as well as the stability of T. spiralis antigens in contaminated meat during food preparations. In animal model, treated WT C57 and W-sh/-sh mice were given 25mg/L of enrofloxacin in drinking 7 days prior infection with T. spiralis, then all treated and untreated mice were infected with 400 T. spiralis muscle larvae, and animals were euthanised at 7 and 14 (d.p.i). In this in vitro study, blood samples and T. spiralis specific antigen and other antigens were analysed by ELISA to assess antibody levels produced. Histological examinations were used to measure lengths of villi and crypts, as well as to enumerate the number of mucosal MCs accumulated in the gut. Results indicated that microbiome enhanced MCs immune responses, which hastened expulsion of parasitic worms. Microbiome increased MCs hyperplasia in WT but failed in W-sh/-sh mice. As expected, higher total IgE observed in WT C57, while extremely reduced in W-sh/-sh mice. However, microbiome had no effect on pathological aspects of crypt hyperplasia, or villus atrophy. Simultaneously, MC hyperplasia, increased T. Ag-specific IgG1, and total IgE reaching their peaks at 14 (d.p.i) along with expulsion of worms. In protective response, microbiome influenced MC responses by boosting MLNs hyperplasia, but not on T cell proliferation. T. spiralis infection stimulated Th2 immune responses with higher levels of IgG1 and IgE instead of Th1 since minimal IgG2a produced. In immunodiagnostics, sensitivity and specificity of ELISA were assessed from a pool of T. spiralis own antigen with other unrelated (Ag)s on immune sera. Results showed that T. spiralis infection sensitised high production of T. Ag-specific IgG1, and moderately stimulated production of IgG2a and IgM, with no detectable IgA and IgE. The assay proved high specificity on T. spiralis since it only picked up relevant T. Ag of its own species from a pool of unrelated (Ag)s in T. spiralis immune sera. In the same way, only H. polygyrus Ag was selected in H. polygyrus immune sera. Moreover, stability of T. spiralis was analysed in different processing conditions of heat, salt, and acid to mimic processing of pork in diagnosis of T. spiralis infection. The assay was stable to boiling temperatures for short time or treatment with low salt and acid contents. Furthermore, ELISA assay was unstable in the diagnosis of T. spiralis infection on T. spiralis Ag mixed with pork protein due to blocking effect of pork protein. In conclusion, microbiome enhances MCs protective and pathological immune responses, but Direct ELISA cannot be used in the detection of T. spiralis in pork. To increase reliability of the effect of microbiome on MCs immune responses, GF mouse model and Antibiotics Treatment method are recommended for future studies. Equally, to overcome the problems of instability of processed meat samples, and cross reactivity among Trichinella species or closely related parasite infections as well as the blocking effect of analyte protein to Direct ELISA assay, LF-RPA diagnostic strip assay and sandwich ELISA are recommended in diagnosis of Trichinella species in pork and domestic animals.Helminth infections predominantly occur in countries with inadequate environmental sanitation. Around 1.5 million people are infected with different helminth species including hookworms, roundworms, and whipworms. Roundworms are commonly isolated in human, and in particular a zoonotic nematode, T. spiralis is crucially important as it infects humans through food chain by consumption of undercooked meat such as pork, or game meat causing diseases which lead to an increased burdens in economy especially medical, educational costs. The need to find suitable, accurate and cost-effective diagnostic approaches, as well as the way to strengthening natural protective and pathological immune responses driven by MCs against T. spiralis is fundamental to pave that way to control and minimizing the risk of infections. Study of the effect of gut microbiome on immune responses is at its early stage, and only few studies have suggested that the presence of microbiome can affect immune responses. In this study we firstly evaluated the effect of microbiome on helminth induced protective and pathological immune responses driven by mast cells during T. spiralis infection. Secondly, we analysed the specificity and relevance of ELISA in the detection of T. spiralis infection, as well as the stability of T. spiralis antigens in contaminated meat during food preparations. In animal model, treated WT C57 and W-sh/-sh mice were given 25mg/L of enrofloxacin in drinking 7 days prior infection with T. spiralis, then all treated and untreated mice were infected with 400 T. spiralis muscle larvae, and animals were euthanised at 7 and 14 (d.p.i). In this in vitro study, blood samples and T. spiralis specific antigen and other antigens were analysed by ELISA to assess antibody levels produced. Histological examinations were used to measure lengths of villi and crypts, as well as to enumerate the number of mucosal MCs accumulated in the gut. Results indicated that microbiome enhanced MCs immune responses, which hastened expulsion of parasitic worms. Microbiome increased MCs hyperplasia in WT but failed in W-sh/-sh mice. As expected, higher total IgE observed in WT C57, while extremely reduced in W-sh/-sh mice. However, microbiome had no effect on pathological aspects of crypt hyperplasia, or villus atrophy. Simultaneously, MC hyperplasia, increased T. Ag-specific IgG1, and total IgE reaching their peaks at 14 (d.p.i) along with expulsion of worms. In protective response, microbiome influenced MC responses by boosting MLNs hyperplasia, but not on T cell proliferation. T. spiralis infection stimulated Th2 immune responses with higher levels of IgG1 and IgE instead of Th1 since minimal IgG2a produced. In immunodiagnostics, sensitivity and specificity of ELISA were assessed from a pool of T. spiralis own antigen with other unrelated (Ag)s on immune sera. Results showed that T. spiralis infection sensitised high production of T. Ag-specific IgG1, and moderately stimulated production of IgG2a and IgM, with no detectable IgA and IgE. The assay proved high specificity on T. spiralis since it only picked up relevant T. Ag of its own species from a pool of unrelated (Ag)s in T. spiralis immune sera. In the same way, only H. polygyrus Ag was selected in H. polygyrus immune sera. Moreover, stability of T. spiralis was analysed in different processing conditions of heat, salt, and acid to mimic processing of pork in diagnosis of T. spiralis infection. The assay was stable to boiling temperatures for short time or treatment with low salt and acid contents. Furthermore, ELISA assay was unstable in the diagnosis of T. spiralis infection on T. spiralis Ag mixed with pork protein due to blocking effect of pork protein. In conclusion, microbiome enhances MCs protective and pathological immune responses, but Direct ELISA cannot be used in the detection of T. spiralis in pork. To increase reliability of the effect of microbiome on MCs immune responses, GF mouse model and Antibiotics Treatment method are recommended for future studies. Equally, to overcome the problems of instability of processed meat samples, and cross reactivity among Trichinella species or closely related parasite infections as well as the blocking effect of analyte protein to Direct ELISA assay, LF-RPA diagnostic strip assay and sandwich ELISA are recommended in diagnosis of Trichinella species in pork and domestic animals
Analysis of multiple Coulomb scattering of muons in liquid hydrogen
Full text linkA comparison is made between experimental measurements of muons passing through the MICE (Muon Ionization Cooling Experiment) liquid-H2 absorber, with a Geant4 (v9.6) Monte Carlo (MC) simulation. The aim was to assess if the accuracy of the multiple Coulomb scattering (MCS) simulation algorithm is consistent with data across two configurations; one with the vessel filled with liquid-H2, and one with the empty vessel. MCS is one of two parallel processes in ionization cooling (IC), a novel beam cooling technique that can achieve significant emittance reduction within the short muon life-time. The analysis is motivated from previous experimental measurements indicating poor predictive performance of MCS of muons through liquid-H2 using various models. In future muon accelerator facilities, ionization cooling channels will use the ionizing collisions during passage through a low-Z absorber to damp beam momentum while re-supplying longitudinal acceleration. MICE concluded data-taking in 2017 and has since demonstrated the performance of IC while has also gathered straight-track data specifically for measurements of MCS. In this thesis, data taken with three beam settings are analysed that delivered beam momenta in the range 143–250 MeV/c at the two absorber configurations. The resulting p-values, expressing the probability of identity between the simulated and measured plane-projected scattering angle distributions are found to be in the range 0.44–0.98, without meaningful differences between the two absorber configurations, indicating that Geant4 (v9.6) accurately predicts MCS of muons through liquid-H2 in the analysed momentum range.A comparison is made between experimental measurements of muons passing through the MICE (Muon Ionization Cooling Experiment) liquid-H2 absorber, with a Geant4 (v9.6) Monte Carlo (MC) simulation. The aim was to assess if the accuracy of the multiple Coulomb scattering (MCS) simulation algorithm is consistent with data across two configurations; one with the vessel filled with liquid-H2, and one with the empty vessel. MCS is one of two parallel processes in ionization cooling (IC), a novel beam cooling technique that can achieve significant emittance reduction within the short muon life-time. The analysis is motivated from previous experimental measurements indicating poor predictive performance of MCS of muons through liquid-H2 using various models. In future muon accelerator facilities, ionization cooling channels will use the ionizing collisions during passage through a low-Z absorber to damp beam momentum while re-supplying longitudinal acceleration. MICE concluded data-taking in 2017 and has since demonstrated the performance of IC while has also gathered straight-track data specifically for measurements of MCS. In this thesis, data taken with three beam settings are analysed that delivered beam momenta in the range 143–250 MeV/c at the two absorber configurations. The resulting p-values, expressing the probability of identity between the simulated and measured plane-projected scattering angle distributions are found to be in the range 0.44–0.98, without meaningful differences between the two absorber configurations, indicating that Geant4 (v9.6) accurately predicts MCS of muons through liquid-H2 in the analysed momentum range
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