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A missional encounter in China: governmentality, relations of power, and eschatological praxis
Get PDFThis thesis examines the encounter of a Protestant missional agent with the state apparatuses of the Chinese Communist Party in the Hu Jintao era. By the construction of an interdisciplinary theo-political framework through the theological concepts of J. Moltmann (supplemented by concepts of J. Metz, R. Niebuhr and J. Ellul) and the non-theological conceptual toolbox of M. Foucault, this study attempts to analyze and interpret in an integrative manner the interacting relationship between the missional agent and respective state apparatuses via collaborative undertakings that were characterized by the productive nature of power and love. Collaborative engagement is argued as dialogical interaction in the anthropological operative dimension within a dynamic web of power and love relations mediated via a politically constructed matrix of governmental rationalities. Theological discernment and historical theo-political analysis of this study point out that, amid the forces of the power of the party-state, which tended to oppress the Christian communities, there was a specific resurgence of possible enlarged spaces that emerged and re-emerged again via the forces of the power of the future in the mission field. Eschatological praxis of the missional agent in the form of missional initiatives functioned to channel reality out of previously pre-defined categories and acted as a force to transform historical events in the missional arena. The Chinese Communist Party can be dominating, but it is not absolute. Dynamic mutuality between the missional agent and the regime was enhanced when power relations were mobilized correlatively
Evaluation of platinum nanoparticles on human platelets
Get PDFPlatinum nanoparticles (PtNPs) are the key catalyst of proton exchange membrane fuel cells (PEMFC); however, their degradation may pose a potential health risk if they are inhaled and translocate across the lungs gaining access to the bloodstream, where they will encounter platelets. Platelets are critical to the cardiovascular system where they maintain haemostasis (leading to cessation of bleeding). On the other hand, excessive activation of platelets underlies a variety of thrombotic diseases including ischaemic stroke and heart attack. Activation of platelets has been observed by nanoparticles including diesel exhaust particles in vitro, nonetheless, not much is known on how the physicochemical properties of the nanoparticles influence platelet activation. This thesis aims to create an array of PtNPs exhibiting negative, positive, and neutral charges, and to investigate their ability to induce activation of human platelets including aggregation. Citrate capped PtNPs were synthesised and characterised by TEM, DLS, zeta potential and XPS for size, surface charge and surface composition. Alkane and polyethylene glycol (PEG) thiols and other surface modifying compounds were used to functionalise these PtNPs to exhibit negative, positive, and neutral charges via ligand exchange and synthesis methods. Following characterisation, functionalisation of PtNPs was met with varying degrees of success. It was revealed the negatively and neutrally charged PtNPs were only partially functionalised by the alkane and PEGylated thiols. Positively charged PtNPs were found to be unstable. Albeit these partially functionalised PtNPs were assessed in platelet activation and aggregation. Negatively charged and neutrally charged PtNPs were unable to induce platelet aggregation, while platelet aggregation was observed by citrate capped PtNP. Platelet aggregation was found to be influenced by the zeta potential of PtNPs
Exploiting additively manufactured lattices to control mechanical properties and drug delivery in bone implants
Get PDFMetal bone implants are used extensively to provide mechanical support, fixation or to fill defects due to disease, aging or trauma. Examples of implant include joint replacement, fracture plates, and fusion cages. These are very successful surgeries; however, failures do occur. The most common causes of bone implant failure are infection and aseptic loosening which can be caused by stress shielding or poor fixation.
Additive manufacturing enables the creation of implants with complex geometries such as lattices which cannot be easily made with conventional manufacturing techniques. Despite lattices being used in medical devices for fixation, and extensively researched for stress shielding their potential to be exploited as drug delivery vehicles has not been fully explored. In this work the novel technique of manipulating lattice geometry to control drug release is proposed.
The mechanical properties of lattices manufactured from Ti-6Al-4V by laser powder bed fusion was investigated. Four lattice designs provided sufficient compressive strength to be weight bearing while having sufficient void volume to fill with a drug loaded biomaterial.
For example BCCZ lattices with a 350 μm strut thickness had an offset stress of 365 ± 7 MPa with a volume fraction of 0.583 ± 0.001. Additionally the effects of strut and wall thickness, lattice rotations during building, loading and a combination of the two, and unit cell size were investigated; to understand which factors were important when designing additively manufactured medical devices.
Secondly, BCCZ and gyroid lattices with volume fractions of 0.2, 0.4 and 0.6 were filled with brushite cement containing 2.5% w/w gentamicin sulphate. The drug release fitted the Korsmeyer-Peppas model with R2 values of at least 0.98 and could be controlled by changing the lattice geometry. There were also statistical differences in the size of inhibition zones of Staphylococcus aureus and Pseudomonas aeruginosa. The presence of brushite cement in the lattice structure did not reduce the compressive strength.
Finally, a coating was developed to immobilise therapeutics to the surface of implants. Albumin was used as a model therapeutic, it was covalently attached via amide bond coupling to PCL which was dip coated onto Ti-6Al-4V coupons. This process was optimised and albumin continued to intrinsically fluoresce on coupon surfaces after immersion for four months in phosphate buffered saline at 37°C.
This thesis focuses on the exploitation of lattices manufactured by laser powder bed fusion to control drug delivery while manipulating the mechanical properties, with a view to using them in hip replacements to treat infection, and spinal interbody fusion cages to improve bone ingrowth
An exploration of detection and management practices for postpartum haemorrhage in low- and middle-income countries: a quantitative survey
Get PDFIntroduction As the leading cause of maternal mortality worldwide, postpartum haemorrhage (PPH) accounts for 27% of maternal deaths each year. With timely detection and management, the majority of PPH-related maternal deaths could be avoided or prevented. One method which could enable this is PPH-related clinical care bundles: a set of three to five discrete evidence-based clinical interventions delivered concurrently or in quick succession. The present study aimed to explore how primary PPH is currently detected and managed during vaginal birth at the E-MOTIVE trial facilities, to what extent the components of the new E-MOTIVE bundle are currently implemented within trial facilities, and what factors influence current PPH detection and management, and the implementation of the E-MOTIVE bundle.
Methods An electronic quantitative survey was conducted in health facilities across four countries: Kenya, Nigeria, South Africa and Tanzania, all of which were selected for participation in the E-MOTIVE trial. In total, 1,009 healthcare professionals completed the survey across 91 trial facilities. Data were analysed descriptively.
Results Visual estimation was the most commonly reported method of blood loss measurement by participants (n=885, 89.5%). Amongst those who indicated that detection of PPH was part of their clinical role, 21.8% (n=216) reported that they use an obstetric drape. Current performance of the E-MOTIVE bundle components varied, with 93.0% (n=929) of participants regularly performing uterine Massage, 92.7% (n=925) administering Oxytocin, 47.8% (n=477) administering Tranexamic acid, 90.8% (n=907) administering IV fluids, and 55.6% (n=555) performing Examination of the genital tract in the delivery room. When exploring methods to improve the detection and management of PPH, 96.0% (n=949) of participants agreed or strongly agreed that they intend to improve their knowledge of PPH. Participants indicated that improving team working (n=838, 90.4%), increasing the availability of supplies (n=757, 81.7%), having all the required supplies in one place (n=744, 80.3%), and more training (n=714, 77.1%), would make it easier to perform multiple PPH management interventions together in a bundle.
Conclusions This research outlines the current PPH detection and management practices of healthcare professionals working in the E-MOTIVE trial facilities. Differences between current practice and the target E-MOTIVE intervention were identified. Current barriers and enablers to the application of the intervention were discussed, and implementation strategies to support the E-MOTIVE bundle are suggested. Future research may further explore descriptive differences found at the country and cadre level
Investigation of the link between splicing and nonsense-mediated mRNA decay in Schizosaccharomyces pombe
No full textNonsense-mediated mRNA decay (NMD) is an evolutionarily conserved translation-coupled process involved in the degradation of transcripts possessing premature translation termination codons (PTCs), including non-PTC-containing transcripts in atypical contexts, to help maintain normal cellular homeostasis. In mammals, the exon junction complex (EJC) of proteins deposited upstream of splice junctions after splicing in the nucleus is believed to link the process of pre-mRNA splicing to nonsense mutation recognition and subsequent transcript degradation. However, current and previous studies have presented evidence of the non-requirement of the EJC proteins in NMD in several eukaryotes. In this study, using several NMD reporter constructs, both intronless and intron-containing, I was able to re-evaluate the effect of nonsense mutations on mRNA decay in Schizosaccharomyces pombe, providing additional evidence on the non-requirement of the EJC in S. pombe NMD. Without an intron, I found that early PTCs up to the second half of a gene’s coding region, including at codon position one, can elicit NMD. Furthermore, I discovered that some PTC-containing transcripts toward the end of the gene’s coding region could result in more mRNA production and more fluorescence of the NMD reporters compared to PTC-less genes. With an intron, NMD sensitivity depended on the proximity of the PTC relative to the intron, with the early PTCs being an exception. I also describe an optimized and efficient protocol of plasmid mutagenesis, including how a 3’ UTR intron could be used in a screen for splicing-dependent NMD suppression via different approaches. Using RNA-seq and differential gene expression analysis, I assessed how endogenous genes behaved without NMD. I found that while some genes are uniquely affected by the deletion of the NMD factors, a subset of genes are co-regulated by the NMD factors. The upregulated genes possess features of NMD-permissive transcripts
Rationally designing strategies to augment checkpoint therapy in cancer
Get PDFCancer immunotherapy, such as immune checkpoint modulation (ICM), has revolutionised the treatment of cancer in recent decades. Unfortunately, only a small fraction of patients respond to the treatments, and they are associated with several immune-mediated toxicities. This project is divided into two research chapters, both aiming to rationally design a combination ICM therapy for the treatment of cancer.
Research chapter 1 focuses on designing a novel treatment for hepatocellular carcinoma (HCC), which is a type of primary liver cancer and is in the top 3 causes of cancer related deaths owing to most patients being diagnosed at advanced stage of the disease. This first research chapter uses reovirus, an oncolytic virus, to prime the tumour microenvironment for subsequent ICM therapy to treat HCC with a specific focus on the immune-mediated mechanism of oncolytic reovirus.
Research chapter 2 focuses on rationally combining antibody-mediated programmed cell death ligand 1 (PD-L1) blockade with other ICM therapy and utilises an immunogenic mouse cancer model. This chapter has a key focus on T-cell tolerance, utilising T-cell receptor (TCR) reporter mice to explore the dynamics of orphan nuclear receptor subfamily 4 (Nr4a) expression following in vitro and in vivo TCR stimulation of Tg4 transgenic mice with agonist tyrosine at position 4 [4Y]-Myelin Basic Protein (MBP) peptide. The data in research chapter 2 using these novel reporter mice reveals that anti-PD-L1 blockade leads to increased susceptibility to peptide rechallenge, lowering the T-cell activation threshold. Furthermore, anti-PD-L1 blockade in combination with OX40 agonism further boosts T-cell activation in this adaptive tolerance model. Finally, it is shown that this combination of anti-PD-L1 blockade with OX40 agonism can lead to enhanced anti-tumour effects
An early insight into the biology and virulence traits of the algal genus Prototheca
Get PDFThe aim of this thesis is to provide a deeper understanding of the basis of pathology in the genus Prototheca, an enigmatic group of pathogenic algae known to infect humans, cattle, and other mammalian hosts. These infections represent burdens on public health, as a result of chronic infection and inefficient treatment, and economic output, as a result of reduced milk production. The mechanisms that allow algae to infect mammalian hosts, and their interactions with mammalian immunity, are currently unknown.
Prototheca is also taxonomically complex, and pathogenic species are distantly related within the genus. Additionally, Prototheca is paraphyletic. The monophyletic clade containing all Prototheca species must also include at least the genera Auxenochlorella and Helicosporidium, forming the AHP lineage.
Much of the existing work on Prototheca is taxonomically restricted, covering a handful of species and largely ignoring the larger AHP lineage. This makes it difficult to meaningfully identify features important for the pathology of Prototheca species, or whether pathogenic AHP species share a common basis for pathology. Thus, this thesis takes a broader view, looking at the wider AHP lineage rather than one or two species. This thesis also considers multiple aspects of pathology, considering that pathology in Prototheca species may be accidental rather than as a result of specific adaptation to infection.
The methods and results of this thesis are varied. A method based on phenol DNA extraction was developed to detect Prototheca in milk, and was used to detect the first reported cases of bovine protothecosis from the UK. A method based on growth curves identified that ability to grow at 37°C separates known pathogenic AHP species from non- pathogenic AHP species. Exposure of AHP species to macrophages revealed that capacity for phagocytosis varies between the AHP species, without an obvious link to pathology. Genome sequencing produced complete organelle genomes for members of the AHP lineage and revealed that Prototheca have lost genes core to the Chlorophyta lineage. Finally, phylogenetics have clarified several relationships within the AHP lineage, revealing two major sub-lineages of the AHP lineage and up to seven boundaries for new genera.
This thesis provides a theoretical and experimental basis for future investigation, allowing for specific questions to be asked of the AHP lineage and more valid comparisons to be made within more closely related members of the lineage
Spinal kinematic variability in people with chronic low back pain
Get PDFLow back pain (LBP) is one of the leading causes of disability globally and chronic non-specific LBP (CNSLBP) accounts for the vast majority of cases. It is widely acknowledged that people with LBP move differently than pain-free individuals. An abundance of research has examined trunk motor control to understand how movement is controlled in the presence of LBP by evaluating both trunk movement patterns and trunk muscle activity. A commonly observed motor adaptation to spinal pain is a change in spine kinematics, such as angular displacement, angular velocity, as well as changes in the variability of these kinematic variables. However, kinematic variability as a motor adaptation to pain in people with CNSLBP has received less attention and still requires further clarification. This thesis presents research to investigate trunk motor adaptations in people with CNSLBP, specifically, by evaluating kinematic variability differences compared to asymptomatic individuals as a critical element of motor performance during repetitive movements. Additionally, the thesis explores factors such as their trunk muscle co-activation patterns and their clinical characteristics in order to gain insights into possible explanations for different movement variability. The first study was a systematic review which confirmed the existence of a different motor pattern in people with CNSLBP, as indicated by differences in spinal kinematic variability compared to asymptomatic individuals during various functional and non-functional repetitive trunk movements. Furthermore, two experimental studies explored the differences in kinematic variability in people with CNSLBP compared to asymptomatic individuals performing two different tasks using the same linear metric to measure variability during repetitive trunk movements. In the second study we applied a novel real-time tracking task using a 3D motion capture system to assess trunk motor control. This study did not reveal any differences in movement variability in CNSLBP people when compared with asymptomatic individuals, however, it showed that movement variability over repeated tracking cycles was associated with the degree of fear of movement in people with CNSLBP. Additionally, the response of those with CNSLBP was consistently delayed in tracking the visual feedback compared to the asymptomatic individuals. The third study tested a lifting task reflecting activities of daily living which detected an increase in movement variability in individuals with CNSLBP, despite performing the task within the same spinal range of motion. Moreover, two additional experiments have introduced the novel application of helical axis (HA) parameters as a measure of spinal kinematic variability during repetitive trunk movements. The fourth study tested the use of HA parameters on asymptomatic individuals which revealed its sensitivity to changes in movement plane and movement speed. The first application of this measure on people with CNSLBP was in the fifth study which revealed an increase in spinal kinematic variability compared to asymptomatic individuals during active trunk repetitive movements, irrespective of the speed or direction of movement. In addition, people with a higher fear of movement showed the lowest kinematic variability. Overall, this thesis further highlights the interaction between physical and psychological features of CNSLBP. The thesis offers new insights into how motor adaptations to spinal pain are present, which suggests the need for tailored interventions to address the unique mechanical presentation of each individual with CNSLBP
A new green bond augmented measure of money: theory and practice
Get PDFThis thesis presents research within empirical monetary economics with a focus on the integration of monetary aggregates and their price dual with green bonds. Chapter I incorporates bonds, including green bonds, alongside traditional monetary assets in the construction of a broad Divisia monetary aggregate for the USA using the Törnqvist-Theil discrete time approximation for the continuous time Divisia Index. The user costs for calculating this index are risk-adjusted and forecasted for capital uncertain assets. The analysis reveals a significant and positive correlation between a broad Divisia monetary aggregate for the USA, including green bonds, and the detrended output gap. Consequently, the broad Divisia monetary aggregate augmented with green bonds can usefully serve as a monetary policy indicator. Green asset augmented Divisia monetary aggregates also have the potential to provide feedback to central banks on an evolving economy and aid in maintaining economic stability and addressing potential political pressures.
Chapter II contributes to the monetary vector autoregressive (VAR) literature as the first work to employ a newly green augmented Divisia price dual as a policy indicator for the USA. Three empirical results are obtained to support the use of green price dual as the policy indicator variable. First, policy shocks have significant effects on both output and price level. Second, user cost is closely correlated with the Federal Funds rate and could be an alternative for that rate as a policy indicator following the Taylor rule. The price dual is useful when the Federal Funds rate becomes stuck at its zero lower bound (ZLB) after 2008. Third, we develop a new VAR model that is not subject to the price puzzles.
Chapter III aims to examine the forecasting performance of newly constructed green-benchmarked Divisia monetary aggregates for the USA output gap. By using the green bonds as the benchmark asset, we successfully construct the green-return benchmarked and green-coupon benchmarked monetary aggregates with the rate of return on 20Y+ green bonds and the coupon rate of 20Y+ green bonds as the benchmark rate, respectively. We also construct the conventional Divisia monetary aggregate and the traditional simple sum monetary aggregate for comparison. We then employ the Markov regime switching vector autoregressive (MS-VAR) model to test the forecasting ability of these monetary aggregates in output gap. The green-benchmarked Divisia MS-VAR models are found to be superior in one-month, three-month, six-month and nine-month ahead forecasts
Advancing flavour/fragrance oils microencapsulation: exploring the impact of core oil on microcapsule characteristics
Get PDFThe aim of the project is to develop simple, industrially scalable encapsulation methods to fabricate biodegradable microcapsules with desirable properties, using either natural waxes by melt dispersion or gelatine/gum arabic by complex coacervation.
L-carvone (LC) and hexyl salicylate (HS) were used as model core oils. Core oils are encapsulated based on the formation of wax microspheres, while addressing the influence of different types of waxes as well as different oil to wax ratios. HS encapsulation efficiency (EE) ranging from 75.7 ± 2.7 to 83.7 ± 1.2 % has been achieved for different types of waxes, which were comparable to those of commercially available melamine formaldehyde (MF) based microcapsules (EE, 75%), and higher than the recently developed microcapsules (EE, 47 ± 11%) using plant-based biopolymers (Chitosan and gum arabic). The Young’s modulus of each wax microspheres determined by the Hertz model had a wide range of values from 28.3 ± 1.4 to 390.7 ± 16.0 MPa, suggesting the availability of wax microspheres for various industrial applications. Moreover, the desirable properties of wax microspheres could be controlled by selecting a certain oil to wax ratio.
Also, gelatine/gum arabic coacervate based microcapsules have been fabricated to encapsulate L-carvone, limonene and hexyl salicylate via complex coacervation. The highest EE (89.0 ± 1.2%) was achieved for HS loaded microcapsules. Their mean apparent Young’s modulus of microcapsules was determined by the Hertz model (668 ± 165 MPa) and the intrinsic Young’s modulus of microcapsules shell was determined
by finite elements analysis (6.2 ± 1.0 GPa). Both the EE and mechanical properties were significantly higher than those of chitosan/gum arabic or commercially formaldehyde-based microcapsules, suggesting the feasibility of gelatine/gum arabic to be utilised in applications for household care, laundry and textile industries. However, LC was not encapsulated well by gelatine/gum arabic microcapsules (EE, 5.0 ± 0.4 %) compared to HS (EE, 89.0 ± 1.2%), evidencing the significant influence of core oil on microcapsule characteristics.
Finally, the physical properties of core oil (linalool, L-carvone, limonene, hexyl salicylate, carvacrol and cinnamaldehyde) were examined in order to evaluate their effects on the capsule morphology and encapsulation efficiency by combining the spreading coefficient and two component surface energy theories. It was found that the spreading coefficient configurations (based solely on thermodynamic considerations) for each oil did not give an accurate prediction of capsule morphology when high molecular weight biopolymers (gelatine/gum arabic) were involved in the system. However, the predicted structural morphology for different oil microcapsules were still holistically consistent with their encapsulation efficiency, which also was found to increase with the decreasing surface polarity of the core oil.
Overall, although wax microspheres and gelatine/gum arabic coacervated microcapsules did not give satisfactory EEs for the encapsulation of LC, the performances (high EE and strong mechanical strength) of these microspheres and microcapsules containing HS looked promising. The impact of both thermodynamic spreading coefficients and surface polarity of each core oil on the formed microcapsule structural morphology and encapsulation efficiency is crucial, providing a useful insight about the engulfing mechanism for oil encapsulation both for academic research and industrial applications
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