A Supervisor for Control of Mode-switch Process

Many processes operate only around a limited number of operation points. In order to have adequate control around each operation point, and adaptive controller could be used. When the operation point changes often, a large number of parameters would have to be adapted over and over again. This makes application of conventional adaptive control unattractive, which is more suited for processes with slowly changing parameters. Furthermore, continuous adaptation is not always needed or desired. An extension of adaptive control is presented, in which for each operation point the process behaviour can be stored in a memory, retrieved from it and evaluated. These functions are co-ordinated by a ¿supervisor¿. This concept is referred to as a supervisor for control of mode-switch processes. It leads to an adaptive control structure which quickly adjusts the controller parameters based on retrieval of old information, without the need to fully relearn each time. This approach has been tested on experimental set-ups of a flexible beam and of a flexible two-link robot arm, but it is directly applicable to other processes, for instance, in the (petro) chemical industry

Molecular characterisation of the extracellular matrix protein 1 gene in lipoid proteinosis in South Africa

Faculty of Health Science Degree of Master of Science in Human Genetics 9809684wLipoid proteinosis (LP) (OMIM 247100) is a rare autosomal recessive disorder that is caused by mutations within the extracellular matrix protein 1 gene (ECM1). The ECM1 gene has been shown to play a role in angiogenesis and connective tissue matrix generation, especially in skin and bone. The role of ECM1 in normal skin development and maintenance is further highlighted by its role in LP and in lichen sclerosis where autoantibodies are raised against ECM1. LP usually presents in the first year of life with a faint or hoarse cry and is due to a hyaline-like material deposited in the mucous membranes of the vocal cords. Gradually (over years) there is diffuse skin infiltration and general skin thickening with a yellow, waxy appearance. There is excessive scarring with scars often appearing at sites of minor injury or stress. In many cases, the eyelids show typical beaded papules. In some cases, calcification of certain aspects of the temporal lobes have been observed, and may or may not be associated with variable neurological, psychiatric and neuropsychological sequelae. Although the prevalence of LP in South Africa is unknown, the disproportionately high number of case reports originating from South Africa indicates that LP is unusually common in certain South African populations, most notably the Coloured population of Namaqualand and the Afrikaans-speaking White population. This may be due to a possible LP founder effect that occurred early during the European colonisation of South Africa. The founder effect was investigated in the South African LP patients by conducting ECM1 mutation and linked marker analysis. The data supported a LP founder effect as the Q276X mutation in exon seven of ECM1 was present in the homozygous state in all LP patients investigated. In addition, the Q276X mutation was associated with a single founder haplotype of 19-12-23-22 (ND1-D1S2343-D1S305-D1S2624). These markers were in significant linkage disequilibrium with each other and with the Q276X mutation. VI As variation within ECM1 may alter properties of skin such as healing and scar formation, ECM1 exons two through five and the first part of exon six were investigated for nucleotide variation using denaturing high performance liquid chromatography (dHPLC) and direct DNA sequencing in three different South African populations. Eight nucleotide variants were identified, of which six were cytosine to thymine transitions. Seven of the eight variants identified were either intronic or synonymous, with one variant being a missense variant, changing a methionine residue to a threonine residue (T130M)

COVID-19-related acute kidney injury and dialysis: What are the outcomes in South Africa?

Introduction: Acute kidney injury (AKI) in hospitalized patients infected with COVID-19 is associated with an elevated mortality rate compared to non-infected patients (39% versus 24%). This is despite a lower prevalence of AKI in COVID-19-infected patients (17 vs 22%). The reasons are multifactorial and have been well documented in developed countries, whereas in developing countries there are scant data. Methods: This study aimed to document the mortality in COVID-19-infected South African patients who required dialysis for AKI. Exclusion criteria included any chronic kidney replacement therapy (transplantation or dialysis). A REDCap survey of South African nephrologists and nephrology fellows registered with the South African Nephrology Society was conducted. The primary outcome was all-cause in-hospital mortality, while additional points of interest included comorbidities, dialysis modality and intervention required. Univariate analysis of mortality predictors was performed. Results: The COVID-19-related AKI mortality rate was 58.9%. Significant predictors included continuous veno-venous haemodialysis therapy, invasive ventilation, use of inotropes and the presence of shock. Ischaemic heart disease, heart failure and admission to a private healthcare facility were associated with lower mortality. No significant associations were found with ethnicity, sex, hypertension, diabetes, HIV infection or the use of other modes of dialysis. Conclusions: In South African patients, we report similar outcomes in critically ill patients requiring dialysis for AKI, relative to international data. The predictors of mortality most likely reflect the severity of the illness in our patients. The data suggest that continuous veno-venous haemodiafiltration or slow low efficiency dialysis may be the preferred dialysis modalities in these patients

Expertise as a domain of epistemics in intensive care shift-handovers

This paper examines how expertise is treated as a separable domain of epistemics by looking at simulated intensive care shift-handovers between resident physicians. In these handovers, medical information about a patient is transferred from an outgoing physician (OP) to an incoming physician (IP). These handovers contain different interactional activities, such as discussing the patient identifiers, giving a clinical impression, and discussing tasks and focus points. We found that with respect to (factual) knowledge about the patient, the OPs display an orientation to a knowledge imbalance, but with respect to (clinical) procedures, reasoning, and activities, they display an orientation to a knowledge balance. We use 'expertise' to refer to this latter type of knowledge. 'Expertise' differs from, and adds to, how knowledge is often treated in epistemics in that it is concerned with professional competence or 'knowing how'. In terms of epistemics, the participants in the handovers orient to a steep epistemic or knowledge gradient when it concerns the patient, while simultaneously displaying an orientation to a horizontal expertise gradient

Characterisation of Lentiviral Vpr Function and Mechanism

Genetic conflict between viruses and their hosts has driven an ‘arms race’, forcing the evolution of both immune defencesdefenses and multiple viral strategies to counteract and evade them. In the case of HIV many of these processes are well characterised – the virus carries with it a set of accessory proteins which target specific host restriction factors. Of these accessory proteins Vpr is the least well understood, with no described role that adequately explains its conservation across all known primate lentiviruses. Unpublished data from our lab indicate that Vpr is able to rescue infection in macrophages from addition of cGAMP, a second messenger protein produced by the cytosolic DNA sensor cGAS which activates antiviral immune signalling pathways. This study first sought to test the hypothesis that Vpr has evolved to counteract cGAS/STING mediated cytosolic DNA sensing using a co-transfection assay to test Vpr proteins from all groups of primate lentiviruses. Initial observations appeared to demonstrate specific degradation of innate immune signalling proteins. It was subsequently shown that HIV-1 M Vpr antagonises expression from all tested co-transfected plasmids. This phenotype was demonstrated to be species specific, and to correlate with both the history of zoonotic transmission and localisation of Vpr to the nuclear rim. Additionally, it was shown that Vpr antagonises NFB signalling activated by TNF, independent of an effect on expression from transfected plasmids, but with the same dependence on nuclear localisation, putatively by the same mechanism. Next, this study characterised an observation that the Vpr from the lentivirus infecting a mona monkey (SIVmon) stimulates NFB signalling. It was hypothesised that the SIVmon Vpr might have molecular binding partners in common with the HIV-1 M Vpr and conditions were optimised for proteomics studies to determine these binding partners. This study provides insights into the role of Vpr in antagonising innate immune sensing. Additionally, overexpression assays have been used widely in the literature describing Vpr. The data presented here indicate that observations using these assays, apparently demonstrating specific degradation of host cellular proteins, should be interpreted cautiously

Supervisory Control of Mode-switch Processes; Application to a flexible beam

Many processes operate only around a limited number of operation points. In order to have adequate control around each operation point, an adaptive controller could be used. Then, if the operation point changes often, a large number of parameters would have to be adapted over and over again. This prohibits application of conventional adaptive control, which is more suited for processes with slowly changing parameters. Furthermore, continuous adaptation is not always needed or desired. An extension of adaptive control is presented, in which for each operation point the process behaviour can be stored in a memory, retrieved from it and evaluated. These functions are coordinated by a “supervisor”. This concept is referred to as supervisory control. It leads to an adaptive control structure which, after a learning phase, quickly adjusts the controller parameters based on retrieval of old information, without the need to fully releam each time. This approach has been tested on an experimental set-up of a flexible beam, but it is directly applicable to processes in e.g. the (petro)chemical industry as well