The need for a whole life framework in electrical power system asset management and the problems with individual silo like asset management system contributions.

The asset management of electrical power systems both in industry and academia currently offers up a wide spectrum of engineering practices and guidance to detect, diagnose and to combat asset deterioration. In doing so research largely aims to better enable enhanced decision or prediction making in single engineering applications such as partial discharge or dielectric condition measurements. This paper reviews the current state of the art as related to electrical asset management and sets out how todays engineering and maintenance heavy approaches are insufficient to meet the nature of the complex adaptive (Generation, Transmission & Distribution) systems. Furthermore this paper explains the need for a truly holistic governance framework capable of managing such complexities for power companies by using complex adaptive system science whilst grounded in the engineering, business and socio-technical attributes that applied engineering makes possible. In addition this paper outlines how utilising retroductive case study with hypothesis framework represents the best approach in creating such a fully holistic asset management capability for power companies

A holistic power systems asset engineering and decision management framework for railway asset managers.

Defining, designing and implementing an asset management system capable of effectively managing assets throughout their life in terms of engineering, financial, digital and stakeholder needs is challenging. Furthermore, governance frameworks of the past have traditionally resulted in 'silo' type asset interventions without considering the total sustainability of system outcomes. In this paper the writers set out a governance framework definition suitable for managing the complex adaptive needs of engineering, financial, digital and stakeholder requirements. In addition, it will set out the components of a framework that can manage complex assemblage of assets by using bottom up aggregation of 'asset realities' and the 'business' or outcomes needs based on stakeholder, socio-economic, technical and or business strategy requirements

Case Study: multi-billion pound infrastructure decision making; a regulatory infrastructure asset management assessment.

This paper evaluates the effectiveness of a hypothesised asset management decision framework implemented with a High-Speed Railway Infrastructure Asset in the U.K over a three-year period. The physical infrastructure asset(s) consists of a complex assemblage of components and classic engineering fraternities; such as Electrical Transmission and Distribution Systems, Civils Assets, Track Systems, Signalling and Communications, Software, SCADA etc, and Assets. In addition, the asset interacts with many U.K and International suppliers, contractors and service providers. Spanning over 218km with large linear assets the railway provides services for high speed trains connecting the U.K to wider European and domestic services, providing significant economic benefit to the U.K Economy, Social Mobility, Urban Development and National Skills development for many Transportation sectors

A novel research approach for whole-life-cycle electrical power systems asset management using retroductive case study method

There are a vast number of complex influences on power systems assets both individually and as a collection of systems of assets. The complexities when governing what and when to intervene with these assets is played out over varying time frames and represents a mixture of engineering, processes, technology, people and economic contributions. The importance of governing power systems olistically has been shown across decades with outages, safety issues, investment needs etc. As of today, research is yet to provide the effective governance framework to manage power systems assets holistically as-a-system; whilst aggregating decisions made at single asset level to generate consistently better outcomes. This paper sets out an approach to researching the phenomenon of asset management applied to power systems by utilising advancements in engineering asset management research and complex adaptive systems; whilst combining industry contributions and technical practices to ensure the suitability of future work. Ultimately the aim of this paper is to provide guidance and method to holistic decision making for power system companies and the management of power systems assets across the whole life

Placental Protein 13 (PP13) – a placental immunoregulatory galectin protecting pregnancy

Galectins are glycan-binding proteins that regulate innate and adaptive immune responses, and some confer maternal-fetal immune tolerance in eutherian mammals. A chromosome 19 cluster of galectins has emerged in anthropoid primates, species with deep placentation and long gestation. Three of the five human cluster galectins are solely expressed in the placenta, where they may confer additional immunoregulatory functions to enable deep placentation. One of these is galectin-13, also known as Placental Protein 13 (PP13). It has a jelly-roll fold, carbohydrate-recognition domain and sugar-binding preference resembling to other mammalian galectins. PP13 is predominantly expressed by the syncytiotrophoblast and released from the placenta into the maternal circulation. Its ability to induce apoptosis of activated T cells in vitro, and to divert and kill T cells as well as macrophages in the maternal decidua in situ suggests important immune functions. Indeed, mutations in the promoter and an exon of LGALS13 presumably leading to altered or non-functional protein expression are associated with a higher frequency of preeclampsia and other obstetrical syndromes, which involve immune dysregulation. Moreover, decreased placental expression of PP13 and its low first trimester maternal serum concentrations are associated with elevated risk of preeclampsia. Indeed, PP13 turned to be a good early biomarker to assess maternal risk for the subsequent development of pregnancy complications caused by impaired placentation. Due to the ischemic placental stress in preterm preeclampsia, there is an increased trophoblastic shedding of PP13 immunopositive microvesicles starting in the second trimester, which leads to high maternal blood PP13 concentrations. Our meta-analysis suggests that this phenomenon may enable the potential use of PP13 in directing patient management near to or at the time of delivery. Recent findings on the beneficial effects of PP13 on decreasing blood pressure d

Design and proof of concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chain

Development of effective vaccines against coronavirus disease 2019 (COVID-19) is a global imperative. Rapid immunization of the entire human population against a widespread, continually evolving, and highly pathogenic virus is an unprecedented challenge, and different vaccine approaches are being pursued. Engineered filamentous bacteriophage (phage) particles have unique potential in vaccine development due to their inherent immunogenicity, genetic plasticity, stability, cost-effectiveness for large-scale production, and proven safety profile in humans. Herein we report the development and initial evaluation of two targeted phage-based vaccination approaches against SARS-CoV-2: dual ligand peptide-targeted phage and adeno-associated virus/phage (AAVP) particles. For peptide-targeted phage, we performed structure-guided antigen design to select six solvent-exposed epitopes of the SARS-CoV-2 spike (S) protein. One of these epitopes displayed on the major capsid protein pVIII of phage induced a specific and sustained humoral response when injected in mice. These phage were further engineered to simultaneously display the peptide CAKSMGDIVC on the minor capsid protein pIII to enable their transport from the lung epithelium into the systemic circulation. Aerosolization of these “dual-display” phage into the lungs of mice generated a systemic and specific antibody response. In the second approach, targeted AAVP particles were engineered to deliver the entire S protein gene under the control of a constitutive CMV promoter. This induced tissue-specific transgene expression, stimulating a systemic S protein-specific antibody response in mice. With these proof-of-concept preclinical experiments, we show that both targeted phage- and AAVP-based particles serve as robust yet versatile platforms that can promptly yield COVID-19 vaccine prototypes for translational development

Exploring and describing nurse managers views on the utilisation of agency nurses in district hospitals in the Cape Metropole

Thesis (MNur)--Stellenbosch University, 2020.ENGLISH SUMMARY : Background: Nursing worldwide is regarded as a scare health human resource and there is literary evidence of an ongoing global nursing shortage. It is essential that nurse managers provide adequate staffing in hospitals. However, this often creates complex dilemmas, because nurse managers rely on agency nurses to amplify the permanent nursing staff due to the shortage. Although agency nursing has become and important strategy to manage the nursing shortage, it brings along associated challenges of quality of care rendered and reported unacceptable conduct. It is for these reasons that the views of Nurse Managers are significant, because it may provide valuable insight and direction to address the issues of quality of care, ethics and nursing standards, including contributing to the national strategy to improve the monitoring of agency nurses. Methods: A qualitative descriptive design was used for this study. A pilot interview was conducted to test the data-gathering instrument for possible errors, to clarify ambiguous questions, and to ensure a common interpretation of the terms used in the data-gathering instrument. No changes were made to the instrument. Data was collected from 14 participants in four focus groups, a face-to-face interview, and a telephonic interview, using semi-structured interview schedules. The interviews were recorded and transcribed verbatim. Thematic data analysis, using the Framework Approach, was guided by the research objectives. Atlas ti. computer software and manual data analysis were done to identify common themes. Ten common themes emerged from the data. Results: The literature indicates that NMs in many countries around the world utilise agency nurses and they experience similar advantages with the utilisation of agency nurses, albeit in varying degrees. These findings further revealed similar common practices for sourcing, deployment and supervision of agency nurses in district hospitals. Other findings were that hospitals have adequate structures and mechanisms in place to monitor and manage agency expenditure. There was also evidence that agency nurses provide quality nursing care. Unanticipated findings include examples of unacceptable conduct of some agencies and agency nurses, the display of caring attitudes towards agency nurses, and nurses from other provinces with different standards, who do agency work in the Western Cape Province. The challenges reported by participants indicated the need fro a monitoring system for the agency nursing industry. Conclusion: Agency nurses make a valuable contribution in assisting hospitals to deliver patient-centered quality care. The dilemmas faced with the utilisation of agency nurses will need further investigation and the development and implementation of policy to regulate the industry.AFRIKAANSE OPSOMMING : Agtergrond: Verpleging word wereldwyd beskou as 'n skaars gesondheids menslike hulpbron en die literatuur toon 'n voortslepende verplegingstekort wereldwyd. Dit is noodsaaklik dat verpleegbestuurders voldoende personeel in hospitale verseker. Soms veroorsaak dit egter komplekse dilemmas, omdat verpleegbestuurders aangewese is op agentskapsverpleegkundiges om die permanente verpleegpersoneel aan te vul as gevolg van die tekort. Alhoewel agentskapsverpleging 'n belangrike strategie geword het om die verpleegtekort te bestuur, bring dit verwante uitdatings wat verband hou met die gehalte van sorg wat gelewer word en onaanvaarbare gedrag word ook ervaar. Om hierdie redes is die siening van verpleegbestuurders van belang, want dit kan waardevolle insig voorsien, en rigting aandui om die kwessies van gehaltesorg, etiek en verpleegstandaarde, insluitene 'n bydrae tot die nasionale strategie om verbeterde monitering van agentskapverpleegkundiges. Metode: 'n Kwalitatiewe ondersoekende studie met 'n filosofies ontwerp is onderneem. 'n Loods-onderhoud is gevoer om die dataversamelingsinstument te toets vir moontlike foute, om dubbelsinnige vrae uit te klaar en ook om te verseker dat daar 'n gemeenskaplike vertolding van die terme in die dataversamelingsinstrument is. Geen aanpassings is aan die instrument aangebring nie. Data is versamel van 14 deelnemers in 4 fokus groepe, 'n persoonlike onderhoud en 'n telefoon-onderhoud deur die gebruik van semi-gestruktureerde vraelyste. Die onderhoude is opgeneem en verbatim oorgeskryf. Tematiese data analise het geskied by wyse van die Raamwerkbenadering en is gelei deur die studie doelwitte. Data analise is gedoen met die gebruik van Atlas ti. rekenaar sagteware, asook met die hand, om gemeenskaplike temas te identifiseer. Resultate: Studie bevindings dui daarop dat verpleegbestuurders in baie lande agentskapverpleegkundiges benut, en hulle ervaar soortgelyke voordele met die gebruik van agentskapverpleegkundiges, alhoewel dit in aard verskil. Verdere bevindinge van hierdie studie dui op soortgelyke gesamentlike praktytke vir die inkoop, uitplasing en toesighouding van agentskapverpleegkundiges in distrikhospitale. Ander bevindinge was dat hospitale voldoende strukture en meganismes in plek het om agentskapspandering te monitor en te bestuur. Daar was ook bewyse dat agentskapverpleegkundiges gehalte verpleegsorg lewer. Onverwagte bevindinge sluit voorbeelde in van onaanvaarbare gedrag van sommige agentskappe en agentskapverpleegkundiges, 'n gesindheid van omgee vir agentskapverpleegkundiges, asook agentskapverpleegkundiges met verskillende standaarde, wie vanaf ander provinsies in die Wes-Kaap agentskapwerk doen. Uitdagings wat die deelnemers gerapporteer het, het gedui op 'n behoefte vir 'n stelsel om die agentskapsindustrie te monitor. Slotsom: Agentskapverpleegkundiges lewer 'n waardevolle bydrae tot hospitale in die lewering van pasient-gesentreerde gehaltesorg. Die dilemmas wat gepaard gaan met die gebruik van agentskapverpleegkundiges moet verder ondersoek word, en die ontwikkeling en implementering van beleid moet geskied om die industrie te reguleer.Master

Investigating the Human-M. tuberculosis interactome to identify the host targets of ESAT-6 and other mycobacterial antigens

Thesis (PhD)--Stellenbosch University, 2012.ENGLISH ABSTRACT: The causative agent of human tuberculosis, Mycobacterium tuberculosis, is an intracellular pathogen that secretes virulence factors, namely ESAT-6 and CFP-10, as substrates of the ESX-1 secretion system. It is hypothesised that these substrates interact with host proteins in a targeted manner in order to elicit a required immune response, and they have been shown to be involved in processes related to pro-inflammatory responses, necrosis, apoptosis, membrane lysis and cytolysis. However, the biological function of ESX-1 substrates during host-pathogen interactions remains poorly and incompletely understood. Therefore, the present study was designed to gain insight into the role of the ESX-1 secretion system substrates in host-pathogen interactions and to identify how M. tuberculosis mediates the response of the human host. In this study, a cDNA yeast two-hybrid library was constructed from human lung mRNA, to identify mycobacterial-host protein-protein interactions that occur within the lung alveoli. The ESX-1 secretion system substrates, ESAT-6 and CFP-10, were cloned in-frame into the pGBKT7 vector, which was used in the yeast two-hybrid system to screen the lung cDNA library in Saccharomyces cerevisiae. The ESAT-6 and CFP-10 screens identified 79 and 19 positive colonies, respectively. Of the total number of clones characterised, only two in-frame inserts were identified with the ESAT-6 screen, corresponding to the human proteins filamin A and complement component 1, q subcomponent, A chain (C1QA). In addition, the screen with CFP-10 also identified C1QA as binding partner. Subsequent in vitro and in vivo experiments were unable to confirm the putative interactions of C1QA with ESAT-6 and CFP-10. However, the interaction between filamin A and ESAT-6 was demonstrated and confirmed by both in vivo co-localisation and co-immunoprecipitation. Furthermore, the degradation of filamin A in the presence of ESAT-6 was shown to be reflective of cytoskeleton remodelling and the induction of cell death. The work presented here suggests that as ESAT-6 gains access to the cytosol, it initiates cell death by inducing destabilisation of the cytoskeleton cell structure. This may possibly be driven by the interaction of ESAT-6 and filamin A. Finally, we also initiated an investigation of the identified putative binding partners (filamin A and C1QA) as possible genetic markers for genetic susceptibility studies to tuberculosis. A case-control analysis was performed involving 604 cases, of which 109 were Tuberculous Meningitis (TBM), and 486 were controls from the South African Coloured (SAC) population within the Ravensmead-Uitsig catchment area. The results of this analysis demonstrated a novel association of a regulatory variant (rs587585) located upstream of the C1QA gene and demonstrated an increasing trend towards increased values in tuberculosis patients with the associated genotype. This study has contributed significantly to our understanding of human-mycobacterial hostpathogen protein-protein interactions and has opened the way for future studies further exploring the consequences and function of the identified ESAT-6-filamin A interaction. It has also led to the identification of a novel genetic association with tuberculosis. Finally, it demonstrates the usefulness of the yeast two-hybrid system to identify potential proteinprotein (host-pathogen) interactions that can lead to additional important and exciting research.AFRIKAANSE OPSOMMING: Die organisme wat tuberkulose veroorsaak, Mycobacterium tuberculosis, is `n intrasellulȇre patogeen wat virulensie faktore afskei, naamlik ESAT-6 en CFP-10, as substrate van die ESX-1 sekresiesisteem. Daar word vermoed dat hierdie substrate met gasheerproteïene in „n teiken wyse interaksie het om `n vereiste immuunreaksie voort te bring. Hierdie substrate is betrokke by prosesse soos pro-inflammatoriese reaksies, nekrose, apoptose, membraanlise en sitolise. Die biologiese funksie van die ESX-1 substrate tydens gasheer-patogeen interaksies word egter tans swak en onvolledig verstaan. Daarom was die huidige studie ontwerp om insig te bekom oor die rol hiervan in gasheer-patogeen interaksies en om te identifiseer hoe M. tuberculosis die reaksie teenoor die gasheer bemiddel. In hierdie studie was `n komplementȇre deoksiribonukleïensuur (kDNS) gis twee-hibried biblioteek gemaak vanaf long boodskapper ribonukleïensuur (bRNS) om proteïen-proteïen interaksies wat in die long plaasvind, te identifiseer. Die substrate van die ESX-1 sekresiesisteem, ESAT-6 en CFP-10, is in volgorde gekloneer in die pGBKT7 vektor en is gebruik om die long kDNS biblioteek in Saccharomyces cerevisiae te ondersoek. In die soeke na interaksies met ESAT-6 and CFP-10, was 79 en 19 positiewe kolonies onderskeidelik geïdentifiseer. Van die aantal klone, was slegs twee volgordes in-leesraam geïdentifiseer met ESAT-6. Hierdie proteïene het ooreengestem met filamin A en “complement component 1, q subcomponent, A chain” (C1QA). Bykomend hiertoe, is C1QA ook geïdentifiseer as „n bindende vennoot met CFP-10. Daaropvolgende in vitro and in vivo eksperimente kon nie die vermeende interaksie van C1QA met ESAT-6 en CFP-10 bevestig nie. Maar die interaksie tussen filamin A en ESAT-6 kon wel gedemonstreer word deur die gebruik van mede-lokalisering en medeimunopresipitasie. Die afbreek van filamin A in die teenwoordigheid van ESAT-6 is ook aangetoon en blyk „n weerspieëling te wees van sitoskelet hermodellering en die induksie van seldood. Die werk wat hier aangebied word, dui daarop dat soos ESAT-6 toegang kry tot die sitosol, inisieër dit seldood deur die destabilisaisie van die sitoskelet selstruktuur. Dit word moontlik aangedryf deur die interaksie van ESAT-6 met filamin A. Laastens het ons `n ondersoek van die geïdentifiseerde bindingsvennote (filamin A and C1QA) as moontlike genetiese merkers vir genetiese vatbaarheidsstudies vir tuberkulose uitgevoer. `n Pasiënt-kontrole studie is gedoen waarby 604 individue ingesluit is, waarvan 109 gediagnoseer is met Tuberculosis Meningitis (TBM), en die ander 486 kontrole individue was van die Suid Afrikaanse Kleurling (SAC) bevolking binne die Ravenmead-Uitsig opvanggebied. Die resultate het „n nuwe assosiasie van „n regulerende variant (rs587585) wat stroomop van die C1QA geen gelokaliseer is, getoon. Hierdie variant het `n verhoogde neiging in tuberkulose pasiënte met die geassosieërde genotipe getoon. Hierdie studie het `n beduidende bydrae gemaak tot ons begrip van menslike-mikobakteriese gasheer-patogeen proteïen-proteïen interaksies. Hierdie resultate het die weg oopgemaak om die gevolge en funksie van die geïdentifiseerde ESAT-6-filamin A interaksie verder te ondersoek. Dit het ook aanleiding gegee tot die identifikasie van `n genetiese assosiasie met tuberkulose. Om saam te vat, hierdie werk bewys die bruikbaarheid van die gis twee-hibriede sisteem, om potensiële proteïen-proteïen interaksies te ontdek wat die moontlikheid het om aanleiding te gee tot addisionele navorsingsvrae.The National Research Foundation,Harry Crossley FoundationMedical Research Council of South AfricaStellenbosch University Postgraduate bursaryProf. Paul van Helde

'n Vergelykende studie tussen die ruimtelike ontwikkelingsraamwerke van Tygerberg en Kaapstad plaaslike owerhede met die van die Kaapse Metropool

Thesis (MS en S)--Stellenbosch University, 2001.ENGLISH ABSTRACT: Various spatial development frameworks are currently being drafted to lead the spatial development patterns of concentrated activities within municipalities and metropoles. The assignment studies the spatial development framework of the Cape Metropole as well as those of the Tygerberg and Cape Town municipalities. An analyses of the different locations and characteristics of the corridors and nodes in these models is made. There are however nodes that are not proposed on the spatial development frameworks but have nevertheless been approved for. development. A comparison of the corridor model is made within the frameworks of the mentioned municipalities. A study is done on whether the corridor model is totally ignored by local authorities or whether it only differs in detail. The effect of the Century City node, which was not proposed in the spatial development frameworks on the development of corridors, is discussed. Backgroud information on the origin and functions of corridors and nodes is gathered through analyses of international examples. Comparison is drawn between these precidents and the Cape Metropole proposals to evaluate their applicability. The conclusion is drawn that the municipalities' and metropole's spatial development frameworks are based on the same principle but differ in their detail structure. Many of the recommendations that are made in the spatial frameworks are difficult to implement. The approval of nodes such as Century City which are not proposed on the frameworks have a negative influence on the economic growth and development of future nodes and corridors as envisaged. Proposals on how to strengthen the implementation process of spatial development frameworks and a possible process for the approval of potential nodes are given.AFRIKAANSE OPSOMMING: Daar is verskillende ruimtelike ontwikkelingsraamwerke wat tans opgestel word om die ruimtelike verspreidingspatrone van gekonsentreerde aktiwiteite binne munisipaliteite en metropole te lei. Die werkstuk ondersoek die ruimtelike ontwikkelingsraamwerke van die Kaapse Metropool asook die munisipaliteite van Tygerberg en Kaapstad. Die korridors en nodusse wat in die modelle voorgestel word, word ontleed in terme van hul eienskappe en verskillende liggings. Daar is nogtans nodusse wat nie in hierdie ontwikkelingsraamwerke voorgestel word nie, maar dit is nieteenstaande goedgekeur vir ontwikkeling. Die werkstuk vergelyk die korridormodel van die Kaapse Metropool (Metropolitaanse Ontwikkelingsraamwerk) met die munisipaliteite se ontwikkelingsraamwerke.Daar word ondersoek of die korridormodel van die metropool heeltemal deur plaaslike owerhede verwerp word of dit net in detail verskil. Die effek van die Century City nodus, wat nie in die ruimtelike ontwikkelingsraamwerke voorgestel is nie, op die ontwikkeling van korridors word ook bespreek. Voorbeelde van internasionale stede word ontleed om agtergrond oor die ontstaan en funksies van korridors en nodusse in te samel. Daarna word bepaal hoe dit op die Kaapse Metropool toegepas kan word. Die gevolgtrekking word gemaak dat al drie raamwerke op dieselfde beginsel gebaseer is maar in detail verskil Daar word baie voorstelle binne die raamwerke gemaak wat moeilik is om te implementeer. Die goedkeuring van nodusse soos Century City wat nie binne die ruimtelike ontwikkelingsraamwerke voorgestel word nie, het 'n negatiewe invloed op die ekonomiese groei en ontwikkeling van die voorgestelde nodusse en korridors. Aanbevelings oor hoe om die implementeringsproses van die raamwerke te ondersteun word gemaak en ook 'n moontlike goedkeuringsproses vir nodusse wat nie binne die ruimtelike ontwikkelingsraamwerke voorgestel word nie