Employed carers' empathy towards people with learning disabilities.

Section A presents the hypothesis that attachment representations determine individuals’ capacities for empathy, which is necessary for sensitive and responsive caregiving. It reviews the evidence pertaining to whether this hypothesis applies within the context of employed caregivers caring for adults with learning disabilities. The evidence is considered in a stepwise fashion, based on four literature searches. The paper concludes by considering the implications of this literature for clinical practice and future research. Section B is an empirical research paper which describes the development of a new questionnaire aiming to measure employed carers’ empathy towards people with learning disabilities. It describes how investigation of the questionnaire’s factor structure illuminated the salient processes that may influence empathy in this specific relational context. It presents evidence of the questionnaire’s construct validity, internal reliability and test-retest reliability. The results are linked to existing literature and recommendations for clinical practice are made. Limitations of the study and directions for future research are considered

Investigation into the therapeutic potential of a clinically compliant amniotic fluid-derived stem cell conditioned media

Necrotising enterocolitis (NEC) is a devastating disease that can affect pre-term infants and if survived can lead to long term intestinal damage. Currently a variety of antibiotics and in extreme cases surgery is required to manage the disease. However, no treatment exists that attenuates the widespread cell death and suppresses the innate pro-inflammatory response whilst promoting regeneration in the intestine thus reducing long term damage and the need for surgery. The discovery of stem cells, in particular multipotent stem cells (MSCs) has shown them to have potent regenerative therapeutic properties. In particular, C-kit+ foetal derived MSCs from amniotic fluid (amniotic fluid stem cells - AFSCs) when introduced into a rat model of NEC increased the survival of animals affected whilst also promoting the repair of damaged epithelial layers. Nevertheless, the ability of stem cells to promote regeneration was independent of transplanted cell engraftment. This led to a paradigm shift in which it was proposed that regeneration was via the secretion of factors acting in a paracrine manner with target cells. This was proven by the introduction of stem cell conditioned media (CM), which mimicked the beneficial effect seen when whole MSCs were introduced. However, much of the MSC CM is produced from non-stressed MSCs. Stressing MSCs has been shown to increase the secretion of paracrine factors and the extracellular vesicles that contain them. Creation of an AFSC CM (AF-CM) under conditions of stress using a protocol created by industrial partners was therefore hypothesised to produce a more potent AF-CM beneficial for regeneration and in particular for the treatment of NEC. Here we characterise the AF-CM under conditions of stress but also in a clinically compliant manner. The AF-CM was characterised for protein and RNA content, which elucidated to a multitude of proteins present but interestingly showed that the majority of RNA present was miRNA. In vitro investigation into AF-CM treatment also showed significant improvements in cellular proliferation and migration capacity whilst protecting from senescence. Furthermore, I showed that AF-CM treatment accelerated the regeneration of skeletal muscle fibres following an established mouse model of acute cardiotoxin damage in vivo, of which could be partly attributed to increased blood vasculature

Equality and Diversity in the NHS

The development of equal opportunities and diversity in the NHS, as a public sector organisation, have been influenced by a combination of ethical, political, legal, and economic business considerations. The principles of equality and fairness are founding principles of the NHS and are central themes of many ethical perspectives, making equality of opportunity a seemingly desirable and congruent objective. UK membership of the European Union and adoption of anti-discrimination legislation coupled with government policies and support of initiatives to redress inequalities has provided a progressive environment for the advancement of diversity. The number of individuals covered by legislation prohibiting specific types of discrimination has increased, so too have the costs to organisations of being found to be illegally discriminating, both monetarily and in terms of reputation. The business case for improving equality of opportunity, particularly emphasised by managing diversity, advocates these as cost effective strategic measures, centred around attracting, retaining and maximising the labour supply, customer satisfaction, market development and organisational success. There are though disproportionate effects of disadvantage and discrimination in the workplace on certain groups that are well documented leading to higher unemployment levels, lower pay and under representation in certain industries and management due to both vertical and horizontal occupational segregation. This dissertation will examine an NHS case study organisation to investigate the scope, objectives and success of equal opportunities and diversity, through the perceptions and views of employees and in the context of a focus on the business case arguments for diversity as a motivating factor for organisations

Social transformation through affirmation of human dignity : a case study of ‘Learn to Earn’

Thesis (PhD)--Stellenbosch University, 2022.ENGLISH ABSTRACT: Given South Africa’s humanitarian crisis, the intention was to explore a possible intervention to address the pervasive poverty and rapidly rising unemployment, by means of a practical theological study. The study aims to ascertain the contribution which spirituality in a Faith-Based Organisation (“FBO”) makes towards attaining social transformation through affirming human dignity. Throughout the study, ‘spirituality’ was given the meaning of the personal and relational side of the Christian faith, which shapes daily life. The evolution of the notion of ‘development’, as an undertaking intended to improve the lives of those experiencing material deprivation, was traced and it was noted how spirituality had long been excluded as a feature affecting the well-being of those to whom poverty upliftment was intended to be addressed. The study therefore argues in favour of a theological interpretation of development, known also as ‘transformation’, having its foundation in a kingdom of God theology with a focus on attaining ‘shalom’. Positioned within the discipline of Theology and Development, this qualitative research study selected a case study as its methodology, within an interpretive paradigmatic perspective, which incorporated the notion of self-reflexivity as an additional dimension of the data interpretation. The unit of analysis of the case study was the FBO, and an in-depth exploration was undertaken in order to understand the work of Learn to Earn (“LTE”), an FBO with an overtly Christian faith expression. LTE professes to focus on the whole person, including the spiritual dimension, in the course of providing skills training to formerly unemployed people in Khayelitsha, Cape Town and Zwelihle, Hermanus. Through empirical research, the integrated spirituality practices of LTE were explored in order to ascertain the extent of social transformation being experienced by its participants. The study’s findings were that the practice of spirituality within LTE resulted in the affirmation of human dignity of participants, in circumstances where there had been a focus on the imago Dei and where the kingdom of God was proclaimed holistically. The result was that ‘marred identities’ of impoverished people were healed as they recovered their true identity and vocation. As a consequence, the affirmation of human dignity through a recovery of vocation played a significant role in the participants overcoming powerlessness, caused by structural injustice. Through their own agency, they were able to escape poverty’s captivity and to progress towards shalom, whereby meaningful social transformation occurred. Based on the empirical evidence relating to the case study of LTE, it can be suggested that this FBO empowers those who are economically deprived, by assisting them to overcome powerlessness, through activating their agency, as their human dignity is affirmed and vocation subsequently recovered. It is suggested that the significant role of the FBO in development work is thereby evident. Recent interest in inclusion of spirituality within development discourse is thus to be welcomed as a beneficial addition to attaining social transformation.AFRIKAANSE OPSOMMING: Gegewe Suid-Afrika se humanitere krisis, is die doel van die navorsing om 'n moontlike intervensie te ondersoek om die heersende armoede en vinnig stygende werkloosheid aan te spreek deur middel van 'n praktiese teologiese studie. Die studie het ten doel om vas te stel watter bydrae spiritualiteit in 'n Geloofsgebaseerde Organisasie (FBO) lewer tot sosiale transformasie deur die versterking van menswaardigheid. In die studie word die betekenis van “spiritualiteit” beskou as die persoonlike en relasionele sy van die Christelike geloof, wat die daaglikse lewe vorm. Die evolusie van die idee van “ontwikkeling” as onderneming met die doel om die lewens van diegene wat materiele ontbering ervaar, te verbeter, is nagevors. Dit was opmerklik dat spiritualiteit lank uitgesluit is as 'n aspek van ontwikkeling wat die welwees beinvloed van diegene tot wie armoede-opheffing gerig word. Die studie pleit dus vir 'n teologiese interpretasie van ontwikkeling, ook bekend as “transformasie”, met as grondslag 'n koninkryk van God-teologie met 'n fokus op die bereiking van shalom. Hierdie studie, wat geposisioneer is in die dissipline van Teologie en Ontwikkeling, is ‘n kwalitatiewe navorsingstudie, wat 'n gevallestudie as metodologie binne 'n interpretatiewe paradigmatiese perspektief gekies het. Die begrip van self-refleksie as 'n addisionele dimensie van die data-interpretasie, is geinkorporeer. Die eenheid van die gevallestudie wat ontleed is, is 'n FBO. 'n In-diepte verkenning is onderneem om die werk van Learn to Earn (LTE), 'n FBO met 'n openlike Christelike geloofsbenadering, te verstaan. LTE fokus op die hele mens, insluitend die geestelike dimensie, in die loop van die verskaffing van vaardigheidsopleiding aan voorheen werklose mense in Khayelitsha, Kaapstad, en Zwelihle, Hermanus. Deur empiriese navorsing is die geintegreerde spiritualiteitspraktyke van LTE ondersoek ten einde die omvang van sosiale transformasie wat deur die deelnemers ervaar word, vas te stel. Die studie se bevindinge is dat die beoefening van spiritualiteit binne LTE, waar gefokus is op die imago Dei en waar die koninkryk van God holisties verkondig is, tot die bevestiging van die menswaardigheid van deelnemers gelei het. Die gevolg was dat “geskende identiteite” van verarmde mense genees is namate hulle hul ware identiteit en roeping herwin het. Gevolglik het die bevestiging van menswaardigheid deur 'n herstel van roeping 'n beduidende rol gespeel sodat die deelnemers magteloosheid, veroorsaak deur strukturele onreg, te bowe gekom het. Deur hul eie agentskap kon hulle uit armoede ontsnap en na shalom beweeg, waardeur betekenisvolle sosiale transformasie plaasgevind het. Gebaseer op die empiriese bewyse wat verband hou met die gevallestudie van LTE, kan voorgestel word dat hierdie FBO diegene wat ekonomies benadeel is, bemagtig om magteloosheid te oorkom, deur die aktivering van hul agentskap, aangesien hul menswaardigheid bevestig word en roeping daarna herstel word. Daar word voorgestel dat die beduidende rol van die FBO in ontwikkelingswerk daardeur duidelik is. Die onlangse belangstelling in die insluiting van spiritualiteit in die ontwikkelingsdiskoers moet dus verwelkom word as 'n voordelige toevoeging tot die bereiking van sosiale transformasie.Doctora

The factors governing stability and combustion intensity in "mechanically" atomised oil flames.

Problems of combustion instability and the need for wider range in firing rates have drawn attention to the need for more fundamental knowledge of the performance and the characteristics of pressure-jet atomized oil flames. A secondary problem is the complication and inconvenience of measurements on full scale equipment. In the present study various operational conditions for a typical modern burner with a pressure-jet atomizer and a swirled air supply were investigated. The variables chosen were fuel rate and spray angle. Data obtained consisted of gas composition, velocity and temperature measurements. The development of a laboratory unit was considered desirable to provide a means of facilitating measurements on flames of this type and a rig was constructed which consisted of a suitable combustion box and 3/10ths scale burner. It was shown that the matching of the spray angle to the air register aerodynamics affected the flame characteristics very markedly, Regions of high unburnt fuel occurred due to fuel penetration and poor mixing outside and downstream of the main part of the flame. The effect of widening the spray angle which usually occurs with wide range types of pressure-jet atomizers at the lower fuel rates was shown to be particularly unsatisfactory, and to effect the black smoke limit. The general course of mixing and the progress of combustion through the flame was deduced from calculation from the gas composition results. The distribution and effects of recirculation were shown from the velocity measurements. These were related to data for simple jets. In particular, it was deduced that internal recirculation in the core was largely responsible for flame stabilization. Theoretically derived scaling criteria were investigated by comparing full scale and model results. These showed that reasonable comparisons were possible between the two, with flames scaled either on the basis of similarity in velocity and relative momentum between spray and air, or on similarity in residence times in the flame. The former was thought probably to be better, Cold flow measurements were made, and showed differences in the size of the central recirculation core between hot and cold but not in the peak velocity to peak velocity diameter early in the flame. Combustion oscillation measurements on a marine boiler produced data which suggested strongly that these were of the "non-acoustic" type. None of the theories so far suggested appear to - ii - account with much accuracy for the observed data. In the course of experimental work various special Instruments for flow measurement were developed. It was concluded that the choice of spray distribution to suit a particular aerodynamic pattern was vital to the optimum performance of the burner. In all the cases investigated this was found to be to some extent imperfect. It is considered that decided improvements could be made to the air distribution in burners of this type. The following possibilities are suggested solutions, the use of a higher degree of swirl and a confining quarl, upstream air injection or the use of multiple oil nozzles and by avoiding devices where the spray angle varies widely over the operating range

High resolution polarimetric imaging of biophysical objects using synthetic aperture radar.

A synthetic aperture microwave near-field system is used to image biophysical objects in order to investigate the nature of radar-target interaction. Two different imaging algorithms for focusing data collected over a two-dimensional planar aperture are investigated. The first of these is the single frequency backward propagation technique which is mathematically simple to implement and provides a high degree of resolution. Secondly, a multifrequency development of the backward propagation algorithm is presented and derived from two separate perspectives. This latter algorithm, known as the auto-focusing algorithm, requires no information about the range of the target from the aperture. Full characterisation by simulation of both algorithms is carried out and different filtering techniques are investigated. The backward propagation algorithm is applied to the polarimetric imaging of three different leafless trees and a sugar beet plant at the X-band frequency of 10GHz. The images so produced demonstrate that the backscattered signal is dependent on the orientation of individual tree elements with respect to the polarisation. Furthermore, multiple scattering terms can be identified within the structure of the tree. The auto-focusing algorithm is applied to the polarimetric imaging of two trees at 10GHz and repeat measurements are made over several months. As with the single frequency measurements, the backscattered signal is dependent on the orientation of individual tree elements relative to the polarisation. The relative contributions from the leaves and branches of the trees to the backscattered signal are assessed and found to be seasonally dependent. Measurements are also carried out to investigate the variation of backscatter from a beech tree with varying incidence angle. It is demonstrated that at small angles of incidence, the leaves are the dominant source of backscatter but at large incidence angles, the branches and trunk of the tree have the greatest contrbution

Mycobacterium tuberculosis subverts negative regulatory pathways in human macrophages to drive immunopathology.

Tuberculosis remains a global pandemic and drives lung matrix destruction to transmit. Whilst pathways driving inflammatory responses in macrophages have been relatively well described, negative regulatory pathways are less well defined. We hypothesised that Mycobacterium tuberculosis (Mtb) specifically targets negative regulatory pathways to augment immunopathology. Inhibition of signalling through the PI3K/AKT/mTORC1 pathway increased matrix metalloproteinase-1 (MMP-1) gene expression and secretion, a collagenase central to TB pathogenesis, and multiple pro-inflammatory cytokines. In patients with confirmed pulmonary TB, PI3Kδ expression was absent within granulomas. Furthermore, Mtb infection suppressed PI3Kδ gene expression in macrophages. Interestingly, inhibition of the MNK pathway, downstream of pro-inflammatory p38 and ERK MAPKs, also increased MMP-1 secretion, whilst suppressing secretion of TH1 cytokines. Cross-talk between the PI3K and MNK pathways was demonstrated at the level of eIF4E phosphorylation. Mtb globally suppressed the MMP-inhibitory pathways in macrophages, reducing levels of mRNAs encoding PI3Kδ, mTORC-1 and MNK-1 via upregulation of miRNAs. Therefore, Mtb disrupts negative regulatory pathways at multiple levels in macrophages to drive a tissue-destructive phenotype that facilitates transmission

Induction of fibroblast senescence generates a non-fibrogenic myofibroblast phenotype that differentially impacts on cancer prognosis

Cancer-associated fibroblasts (CAF) remain a poorly characterized, heterogeneous cell population. Here we characterized two previously described tumor-promoting CAF sub-types, smooth muscle actin (SMA)-positive myofibroblasts and senescent fibroblasts, identifying a novel link between the two

Mechanisms underpinning the permanent muscle damage induced by snake venom metalloprotease

Snakebite is a major neglected tropical health issue that affects over 5 million people worldwide resulting in around 1.8 million envenomations and 100,000 deaths each year. Snakebite envenomation also causes innumerable morbidities specifically loss of limbs as a result of excessive tissue/muscle damage. Snake venom metalloproteases (SVMPs) are a predominant component of viper venoms, and are involved in the degradation of basement membrane proteins (particularly collagen) surrounding the tissues around the bite site. Although their collagenolytic properties have been established, the molecular mechanisms through which SVMPs induce permanent muscle damage are poorly understood. Here, we demonstrate the purification and characterisation of an SVMP from a viper (Crotalus atrox) venom. Mass spectrometry analysis confirmed that this protein is most likely to be a group III metalloprotease (showing high similarity to VAP2A) and has been referred to as CAMP (Crotalus atrox metalloprotease). CAMP displays both collagenolytic and fibrinogenolytic activities and inhibits CRP-XL-induced platelet aggregation. To determine its effects on muscle damage, CAMP was administered into the tibialis anterior muscle of mice and its actions were compared with cardiotoxin I (a three-finger toxin) from an elapid snake (Naja pallida) venom. Extensive immunohistochemistry analyses revealed that CAMP significantly damages skeletal muscles by attacking the collagen scaffold and other important basement membrane proteins, and prevents their regeneration through disrupting the functions of satellite cells. In contrast, cardiotoxin I destroys skeletal muscle by damaging the plasma membrane, but does not impact regeneration due to its inability to affect the extracellular matrix. Overall, this study provides novel insights into the mechanisms through which SVMPs induce permanent muscle damage