An audit of endocrine dysfunction in children with craniopharyngiomas at Red Cross Children's Hospital and Groote Schuur Hospital from 1976 to 2004

Background: Craniopharyngiomas account for 6-10% of childhood brain tumours and are the third most common intracranial tumours of childhood. Despite their benign histological appearance, they are often associated with a poor outcome and have significant associated morbidity. Aim: To analyse the data of children with craniopharyngiomas at Red Cross Children's Hospital and Groote Schuur Hospital from 1976 to 2004 with respect to age at presentation, presenting symptoms and preoperative and post-operative endocrine dysfunction. Patients and methods: The records of 45 children aged between 9 months and 13 years were reviewed. The majority of children in the study were aged between 5 and 10 years. There was a considerable delay in the diagnosis in most cases especially in areas outside of Cape Town. Pre-operative tests prior to 2000 were incomplete but have improved since then. Twenty nine percent of our patients had a near total excision of the craniopharyngioma and 29% had partial excisions necessitating adjuvant radiotherapy. The endocrinological, neuro imaging and presenting symptoms were analysed and post-operative tests were reviewed. Where possible neuropsychiatric assessments were accessed as well in order to assess long term neurocognitive deficits Results: The age of presentation of craniopharyngiomas in our group of patients was much younger than in other studies with the largest group of affected children being between 5 and 10 years of age. The most common presenting symptoms in this group were headaches (62%) and visual disturbances (57%). Sixty four percent of the children had preoperative endocrine testing for pituitary dysfunction of which 59% were ACTH and TSH deficient and only 38% were growth hormone deficient. After surgery multiple endocrinopathies were universal with 56% of children having pan hypopituitarism at follow up. There was no reversal of pre-existing hormone deficits after surgery. The management of craniopharyngiomas remains controversial. Twenty nine percent of our patients had a near total excision and 29 % had a partial excision combined with radiotherapy with a further 6 patients receiving intratumoral bleomycin for recurrences. Post operatively the majority of children were on replacement therapy but only 6 patients (14%) received human growth hormone or are receiving human growth hormone currently due to a lack of funds to provide human growth hormone for children with growth hormone deficiency. Seventy percent of the children had central diabetes insipidus post operatively reflecting posterior pituitary damage. Our overall survival rate from 1976 to 2004 was 91 % with a mortality rate of 13%. Most of the deaths were attributed to recurrences of the craniopharyngioma and the complications of bleomycin treatment. Conclusion: Craniopharyngiomas remain tumours associated with significant morbidity. Total excision of the tumour remains a favourable option but the proximity of the craniopharyngioma to the pituitary gland and optic tracts results in devastating sequelae. Although the medical and surgical management of craniopharyngiomas has improved, a significant number of patients had endocrine sequelae. The management of craniopharyngiomas in an African context compares favourably internationally but with limited resources especially with regard to growth hormone replacement, a large proportion of our children are not receiving optimal treatment

The effectiveness of product placement in music videos: A study on the promotion strategies for brands and products to target the Y generation in Johannesburg

Product placements are strategic brand placements within media that are meant to be noticed by the consumer, to further influence purchase intentions. Placements in music videos have grown in recent years however, there is little research on placements in this medium and available research has not measured the influence of product placement on purchase intention. The study addressed the gap where product placement in music videos was under researched. This paper investigated the effectiveness of brands and products placements in music videos in influencing the purchase intentions of the Y generation population living in Johannesburg. A self-administered research questionnaire was used to collect data through a quantitative research method by convenience sampling of 420 randomly chosen respondents, aged between 18-27, obtained from the University of the Witwatersrand and Johannesburg. A six minute music video stimulus was used for respondents to base their opinions about placements. The results indicate reliability of the constructs in the model developed as Cronbach Alphas were greater than 0.6 for the variables. The main findings show the variables individual factors and execution stimulus are significantly related to brand recall, brand recognition and brand choice. In turn, brand recall, brand recognition and brand choice influence the consumer’s purchase intentions. The strongest linear relationship existed between brand choice and purchase intention. Placement strategies are equally effective for consumers in the Y generation of differing genders, income brackers and age groups. The research reveals that music videos are an effective platform to reach the targeted Y generation population and the model adapted for placements in music videos shows the stages of the processing in the consumer’s mind from exposure to placements to the final purchase intention. The findings contribute to the knowledge of strategies marketers should use to promote brands and products to effectively target the South African Y generation.KIM201

Kidney transplant recipients possess less depressing plasma than healthy controls in KwaZulu-Natal (South Africa) – a paradoxical observation

Background: The reduced activation of lymphocytes of patients on immunosuppressive drugs is well documented. Human plasma has been reported previously to play a role in lymphocyte proliferation. Several factors, including alpha globulin and lipoproteins, have been proposed as modulators of lymphocyte proliferation. Aim: To measure the ATP response of peripheral blood mononuclear cells (PBMCs) from kidney transplant patients and healthy controls following phytohaemagglutinin (PHA) stimulation and to compare the effect of plasma of transplant recipients and of healthy controls on lymphocyte activation. Methods: Peripheral blood mononuclear cells from the blood of healthy controls and kidney transplant patients on regimens based respectively on cyclosporine, sirolimus and tacrolimus, were separated by density gradient centrifugation. Cells were counted and incubated overnight with and without PHA. The luciferin–luciferase enzyme reaction, which induces bioluminescence, and the Turner Biosystem luminometer were used to measure intracellular ATP levels in relative light units, which were converted to ng/mL using an ATP standard curve. A chi-squared test using the Instat 3 program (Graphpad®) was used to compare results. Results: PHA stimulation of PBMC from healthy individuals produced a 47% increase in ATP production. This increase was reduced to 31% when transplant patient plasma was added (P < 0.05). However, when plasma from healthy controls was added instead, paradoxically, the ATP production decreased further to 14%. A similar difference between patient and control plasma was recorded using PBMCs from transplant patients. The reduction in ATP production was the greatest in PBMCs from transplant patients on the tacrolimus-based regimen (P = 0.0388). Receiver operator characteristic (ROC) for ATP level revealed an area under the curve of 0.986. The cut-off value of ATP level between kidney transplant and control using the Youden index was 595 ng/mL, with a sensitivity of 93.3% and specificity of 99.9% Conclusion: Plasma isolated from patients on immunosuppressive drugs suppressed the response of lymphocytes to PHA stimulation. Paradoxically, plasma from healthy controls suppressed T cell activation even more severely. If confirmed in a more extensive study, this observation may be used to influence the choice of replacement fluid in the practice of plasma exchange in transplantation. Keywords: plasma, peripheral blood mononuclear cells, T cell &nbsp

Reimagining the Dream : decolonising Academia by putting the last first

University of Colour in Amsterdam demonstrated against the neoliberal university and the perpetuation of coloniality in the curricula. Rhodes Must Fall in Cape Town specifically focused on the Fanonian concept of ‘putting the last first’. Both Rhodes Must Fall and the University of Colour centred historically marginalised voices as an aim of the decolonised university. The book argues that epistemic justice requires an unlearning and relearning of being/becoming that is the decolonised self; reimagining the relationship between pedagogy and community, theory and lived experience. It attempts to rethink theoretical frames such as Freudian psychoanalysis from a decolonial feminist perspective. This books seeks to share and encourage more dialogue towards achieving decolonised universities.Wetensch. publicati

Étude du rôle du récepteur ERa-36 dans la signalisation non génomique des oestrogènes

We study a novel splice variant of ERa, named ERa36, and its involvement in estrogen non genomic signaling. Unlike ERa, this variant has main cytoplasmic/plasma membrane localization and alternative splicing confers it with a unique, previously unidentified C-terminal domain. Interestingly, we found that ERa36 C-terminal domain contains a putative MAPK binding D-Domain for the serine/threonine kinase ERK2. This domain is a docking site for members of the MAPK family. Coupling in-vitro and in-cellulo approaches, we demonstrated that ERa36 binds specifically to ERK2 following estrogen, as well as clinical anti-estrogen (tamoxifen) stimulation.We demonstrated that ERa36 binding to ERK2 inhibits the latter’s dephosphorylation by the dual phosphatase MKP3, thereby leading to a sustained ERK activation. This mechanism had profound effects on ERK’s downstream molecular targets. In fact, pharmacological inhibition of the ERa36/ERK2 interaction abrogated the phosphorylation of Paxillin, which in turn led to a downregulation of CyclinD1 transcription.Futhermore, IHC analysis of ERa36 expression in 175 patient breast tumors revealed that its expression constituted an independent predictor of distant metastasis and influenced on overall survival. In conclusion, ERa36 expression could constitute a new biomarker in breast cancerNous avons étudié un nouveau varant d'épissage de ERa, nommé ERa36 et son implication dans la signalisation non génomique des œstrogènes. Contrairement à ERa, ce variant a une localisation majoritairement cytoplasmique et membranaire. Il possède une partie C-Terminale unique due à l'épissage alternatif. Nous avons découvert que le domaine C-Termonal de ERa36 contient un D-Domain, qui lui confère la capacité de se lier directement avec des protéines de la famille MAPK. En utilisant des approches in-vitro et in-cellulo, nous avons démontré que ERa36 se lie spécifiquement à la kinase ERK2 en réponse d'une stimulation ostrogénique ou anti-ostrogénique. Nous avons démontré que ERK2 lié à ERa36 lui conférait une résistance à la déphosphorylation par la phosphatase MKP3, conduisant ainsi à une activation soutenue de la voir ERK. Ce mécanisme a des effets profonds sur les cibles de ERK. En effet, l'inhibition pharmacologique de l'interaction ERa36/ERK2 diminue la phosphorylation de la Paxilline, qui a son tour conduit à une répression de la Cycline D1. En plus de ces observations, nous avons démontré, en étudiant l'expression de ERa36 par IHC dans 175 tumeurs de sein, que son expression était un facteur prédictif de métastases à distance et conduit à une diminution de la survie globale. Ce travail pourrait amener à dire que l'expression de ERa36 constitue un nouveau biomarqueur dans le cancer du sei

Science et transcendance : accord ou désaccord ? Éléments de réflexion historique et épistémologique

This paper studies the connection between science and spirituality in the work of Georges Lemaître – scientist and believer, one of the main founders of modern cosmology. Our research questions the nature and role of that connection during a major landmark in the history of science, more generally in the history of thought. The word spirituality is understood here as the search for the divine, for truth. This approach results in a deeper understanding of the beginnings of the “big bang” theory. Nous proposons ci-après l’étude de la relation entre science et spiritualité chez Georges Lemaître, savant et croyant, un des acteurs principaux de la fondation de la cosmologie moderne. Il s’agit d’explorer la nature et le rôle de cette relation lors d’un épisode important de l’histoire des sciences, plus généralement de l’histoire de la pensée. Le mot spiritualité est ici entendu au sens suivant : l’idée et la recherche du divin, du vrai. Il résulte de la présente approche une appréhension élargie de la prime histoire de la théorie dite du « big bang »

Studies on the application of biocontrol agents for the control of seedling diseases.

Thesis (M.Sc.Agric.)-University of Natal, Pietermaritzburg, 2002.The controlled environment of greenhouses, the high value of crops, and the limited number of registered fungicides offer a unique niche for the biological control of plant diseases. During the past ten years, over 80 biocontrol products have been marketed worldwide. A large percentage of these that have been developed in greenhouses could predominate over chemical pesticides in the same way that biological control of greenhouse insects predominated in the United Kingdom. A review of the literature was undertaken to obtain information on biocontrol agents with specific reference to Trichoderma and Gliocladium spp. Literature on the application, types of formulations, limitations in formulation, registration and commercialization of these biocontrol agents were obtained. Trichoderma harzianum Strain KMD has been used successfully as a biological control agent against several soil-borne plant pathogens. Biological control agents should possess several desirable characteristics, including, ease of preparation and application, stability during transport and storage, abundant production of viable propagules and good shelf-life. A strain of Trichoderma harzianum KMD with potential biocontrol activity was used to determine the effect of culture conditions on spore shelf-life. The influence of four growing media were investigated on the spore ultrastructure and shelf-life, using a basal salts medium with C:N ratios of 3 and 14, and pH's of 4.0 and 7.0. Mycelial development and sporulation were positively affected by acidic conditions (pH 4.0). The effect of these culture parameters on viability and shelf-life were evaluated by counting colony forming units (c.f.u) before and after seven days of storage at 75% relative humidity (rH): The effect of carbon concentration on spore viability after seven days of storage was also determined by increasing concentrations of glucose while a constant C:N ratio of 3 or 14 at pH 4.0 was maintained at a 75% rH. Increasing carbon concentration and C:N ratios increased spore production times. Spore viability was greatest when harvested from a medium with a C:N of 14 at pH 4.0 even when storage time was increased to 45 days and rH was reduced to 12%. Ultrastructural studies showed that spores had two cell wall layers, with the outer being more electron-dense than the inner layer. This layer is the spore's first defense against adverse conditions. Spores obtained from this medium were larger, germinated better and had a longer shelf-life than spores from C:N 3 medium, possibly because the two cell wall layers acted as a thicker barrier against adverse conditions. Increasing carbon concentration, while maintaining a constant C:N ratio of 3 or 14 at pH 4.0 slowed down spore production. Viability of spores were similar when introduced on media with variable carbon concentrations but fixed C:N ratios. The ultrastructural differences and shelf-life studies, confirmed empirical results from liquid fermentation studies, that the pH and C:N ratio of the medium upon which spores of T harzianum KMD strain KMD were produced have critical effects on physical and chemical structure of the spores and viability. This, in turn, affects critical parameters for biocontrol agents spore germination and shelf-life. Ultrastructural studies of mycoparasitism of T harzianum KMD on a soil-borne pathogen, Rhizoctonia solani were investigated. The modes of antagonistic action by Trichoderma in biological control have not been fully elucidated. However several mechanisms have been described, such as mycoparasitism, antibiotics, production of inhibitors, which have been identified and shown to suppress soil-borne pathogens. Mycoparasitic activities of T harzianum KMD against R. solani were studied using in vitro bioassays and Scanning electron microscopy (SEM). The fungal growth in dual cultures revealed that T harzianum KMD made hyphal contact with the pathogen within four days of inoculation, leading to an inhibition of pathogen growth. SEM observations showed that T harzianum KMD bound firmly to R. solani hyphae by coiling around the hyphae. Penetration of the pathogens hyphae occurred by the formation of hooks, haustoria and appressoria-like structures by T harzianum KMD, followed by cell disruption. The pathogen's hyphae disintegrated and collapsed upon contact with T harzianum KMD. It is hypothesized that the outcome of the interaction of antagonist and pathogen was most likely determined by initial hyphal contact that triggered a series of events in pathogen destruction. An experimental trial was undertaken to evaluate various formulations if T harzianum KMD and Gliocladium virens Strain MM1 for growth stimulation and biocontrol of R. solani and Pythium sp. on a variety of crops under greenhouse conditions using three application techniques at various dosages. Preparations of isolates of biocontrol agents T harzianum KMD, G. virens MM1 and Bacillus subtilis Strain AW57 were evaluated for their efficacy in enhancing growth and preventing damping-off caused by Pythium sp. and R. solani on a variety of crops namely cabbage, cucumber, Namaqualand daisy and Eucalyptus. Percentage survival and plot weights were measured after 3-4 weeks of growth. The preparations that were used included chlamydospores of biocontrol fungi in milled oats, powders containing conidia in an experimental compound, an oil base, and a commercial product. Formulations of bacteria were prepared with and without Nutristart. The evaluation of three delivery methods were used namely, a seed coating using an adhesive, Pelgel®, capping (a preparation is capped on the surface and incorporated into planting media) and as a drench (preparation drenched on seed at planting). Various dosage levels 0.25, 0.5, 1, 5 and 10g/1 of each formulation was mixed with water and drenched on seed at planting. Growth promotion of seedlings varied for the different formulations of different biocontrol organism. Overall, plot weight was significantly increased on all crops tested. Plant growth of seedlings was consistently increased by all conidial formulations of T. harzianum KMD and G. virens MMI. The best application technique that effectively delivered the biocontrol agents to the target was seed treatment followed by drenching and capping. Most formulations significantly increased plot weight on all seedlings ranging from 2000-5000% when compared to controls and percentage survival was comparable to the controls. In most instances it was recorded that all biocontrol organisms effectively enhanced growth of seedlings equally well irrespective of other main effects. Most formulations of the different biocontrol organisms significantly reduced damping-off caused by Pythium sp. on eucalyptus and Namaqualand daisy. Formulations of T. harzianum KMD prepared with chlamydospores in milled oats and prepared with conidia effectively reduced damping-off on eucalyptus and Namaqualand daisy by 8-31% when compared to the controls. It was observed that biocontrol organisms T. harzianum KMD and G. virens MMI effectively reduced damping-off better than B. subtilis AW57. To effectively reduce damping-off caused by Pythium sp. seed treatment was the best application technique to deliver the biocontrol agent to the target. Biocontrol of damping-off caused by R. solani was achieved on all crops by all formulations of T. harzianum KMD, G. virens MMl and B. subtilis AW57. Disease was reduced by 1000 fold with the application of biocontrol organisms when compared to disease controls. Conidial formulations performed better in reducing disease than formulations prepared with chlamydospores applied as a drench or a seed treatment. In most instances the best dosage to apply formulations were doses that ranged from l-5g/1 for both growth stimulation and biocontrol of soil-borne pathogens. Severe stunting of seedlings occurred at high dosages of 109/I. The compatibility of the biocontrol agent T harzianum KMD with selected fungicides were determined on a variety of crops under greenhouse conditions. A commercial formulation of T harzianum KMD was used for this investigation. An in vitro assay was used to determine the sensitivity of T harzianum KMD to a range of rates of two fungicides, Benlate® and Previcur®. Trichoderma harzianum KMD was found least sensitive to both fungicides after 15 days of incubation at 25°C. The compatible mutants resulted in a lack of sporulation even when induced with UV light. Greenhouse trials were then carried out on cabbage, cucumber, Namaqualand daisy, eucalyptus and tomato. It was confirmed that T harzianum KMD achieved better growth and biocontrol activity against R. solani and Pythium sp. when applied without fungicides to infested and non-infested composted pine bark. Trichoderma harzianum KMD was only compatible to fungicides when applied as a seed treatment prior to planting. As a disease integrated management programme, seed treatment application of T harzianum KMD may be compatible with fungicides for control of damping-off of seedling diseases caused by R. solani and Pythium sp. The effect of environmental stress (oxidative injury, cold and drought) on the growth enhancement of a variety of greenhouse crops by a commercial formulation of T harzianum KMD was evaluated. In an absence of a disease colonization by T harzianum KMD on maize and cucumber roots in rhizotron studies increased root area by 3104 mm(2) and 1787, 48 mm(2) respectively. Oxidative stress was carried out by applying 0.05% NaOCl, to cabbage, cucumber and tomato seeds. This stress did not reduce vigor of seedlings and hence the effect of subsequent treatment with T harzianum KMD on stressed seeds was not determined. Treatments of imbibed but unemerged seeds of cucumber, tomato and white grain maize in cold temperatures (5-100C night/day) for varying periods reduced subsequent growth. Seeds treated with cold stress and T harzianum KMD did not display any growth enhancement. On cabbage, cucumber, tomato and white grain maize seeds sown in various media, which induced various levels of drought and water logging conditions, were not enhanced when seeds were coated with T harzianum KMD. Overall, T. harzianum KMD did not enhance growth under stressed conditions of oxidative injury, cold and drought. The results presented in this thesis shows that T harzianum KMD has potential against soilborne pathogens namely Pythium sp. and R. solani under greenhouse conditions. Applying conidial formulations of T harzianum KMD using seed treatment and applying it at the correct dosage may increase the turnover of seedling production in nurseries. Trichoderma harzianum KMD can replace toxic fungicides and. fumigants under greenhouse conditions. More trials and research are needed on a wider variety of crops and diseases if growth promotion and biological control of T harzianum KMD are to be fully exploited

Optimising pulp and paper mill sludge through alternate end of life pathways: enabling the transition towards circularity within the pulp and paper industry.

Masters Degree. University of KwaZulu-Natal, Durban.Globally the pulp and paper industry (PPI) is regarded as one of the most polluting industries in terms of land, air and water pollution, requiring large quantities of process waters. PPI’s process fibres of different origins i.e. virgin fibres, recycled fibres and non-wood fibres. The source of fibre and manufacturing processes employed determines the quantities and composition of wastes generated. Currently most PPIs, globally follow a linear economic model in which wastes generated are landfilled and is not sustainable as we strive towards a shared goal of carbon neutrality. Limited renewable natural resources and landfill airspace are facing increased demands with the latter being non-renewable. Common waste management methods of pulp and paper mill sludge (PPMS) include incineration prior to landfilling, and by enabling a transition towards a circular economy will facilitate the addition of economic value to ‘wastes’ generated. Adopting circularity facilitates the utilisation of alternate pathways by maximising the benefits posed by such resources, simultaneously reducing quantities of waste requiring landfilling. Increased levels of sustainability can be achieved through mitigating the everincreasing demands placed on limited natural resources through reuse and recycling efforts. This research which was a desktop study focused on alternate waste management approaches on PPMS, exploring of alternate end-of-life pathways facilitating landfill diversion, and increase circularity within the PPI. The pathways explored are relevant globally and within a South African context such as the use of PPMS as a soil conditioner and compost, conversion into an energy pellet, anaerobic digestibility, reuse within the pulp and paper industry and mineral based products and as a landfill cover material. They could be used proactively in anticipation of extreme climatic conditions posed by climate change in efforts of reducing our vulnerability to such risks. Circularity within the PPI will allow for the conservation resources like water, soils and wood. Results from this study highlighted the viability of sustainable integrated waste management of the PPI. Pathways explored allow for the PPI shifting away from the cradle-to-grave and towards a cradle-to-cradle approach of the PPI’s wastes. The results also displayed great potential in integrated waste management systems with benefits posed to economic, social and environmental spheres

Genetic determinants of Nef-mediated CD4 and HLA class I down-regulation differences between HIV-1 subtypes B and C

BACKGROUND: HIV-1 subtype C Nef sequences have a significantly lower ability overall to down-regulate CD4 and HLA-I than subtype B Nef sequences. Here we investigated whether Nef amino acids differing in frequency between HIV-1 subtypes B and C explain lower CD4 and HLA-I down-regulation ability of subtype C. FINDINGS: Subtype-specific mutations were introduced into representative subtype B and C Nef sequences and the CD4 and HLA-I down-regulation ability of these mutants was measured by flow cytometry in a CD4+ T cell line. Subtype C consensus 20I and subtype B consensus 20M reduced and increased HLA-I down-regulation respectively, and the S88G immune escape mutation (which is significantly more frequent in subtype C than subtype B) reduced CD4 and HLA-I down-regulation. CONCLUSIONS: Our data suggest that these subtype-specific differences may partly contribute to inter-subtype functional differences, and identification of an immune escape mutation – S88G – that impairs Nef function is of relevance to vaccine design