Drug safety Africa: An overview of safety pharmacology & toxicology in South Africa.

This meeting report is based on presentations given at the first Drug Safety Africa Meeting in Potchefstroom, South Africa from November 20-22, 2018 at the North-West University campus. There were 134 attendees (including 26 speakers and 34 students) from the pharmaceutical industry, academia, regulatory agencies as well as 6 exhibitors. These meeting proceedings are designed to inform the content that was presented in terms of Safety Pharmacology (SP) and Toxicology methods and models that are used by the pharmaceutical industry to characterize the safety profile of novel small chemical or biological molecules. The first part of this report includes an overview of the core battery studies defined by cardiovascular, central nervous system (CNS) and respiratory studies. Approaches to evaluating drug effects on the renal and gastrointestinal systems and murine phenotyping were also discussed. Subsequently, toxicological approaches were presented including standard strategies and options for early identification and characterization of risks associated with a novel therapeutic, the types of toxicology studies conducted and relevance to risk assessment supporting first-in-human (FIH) clinical trials and target organ toxicity. Biopharmaceutical development and principles of immunotoxicology were discussed as well as emerging technologies. An additional poster session was held that included 18 posters on advanced studies and topics by South African researchers, postgraduate students and postdoctoral fellows

Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS)trial

Background: In laboratory animals, exposure to most general anaesthetics leads to neurotoxicity manifested by neuronal cell death and abnormal behaviour and cognition. Some large human cohort studies have shown an association between general anaesthesia at a young age and subsequent neurodevelopmental deficits, but these studies are prone to bias. Others have found no evidence for an association. We aimed to establish whether general anaesthesia in early infancy affects neurodevelopmental outcomes. Methods: In this international, assessor-masked, equivalence, randomised, controlled trial conducted at 28 hospitals in Australia, Italy, the USA, the UK, Canada, the Netherlands, and New Zealand, we recruited infants of less than 60 weeks' postmenstrual age who were born at more than 26 weeks

The bii4africa dataset of faunal and floral population intactness estimates across Africa’s major land uses

Sub-Saharan Africa is under-represented in global biodiversity datasets, particularly regarding the impact of land use on species’ population abundances. Drawing on recent advances in expert elicitation to ensure data consistency, 200 experts were convened using a modified-Delphi process to estimate ‘intactness scores’: the remaining proportion of an ‘intact’ reference population of a species group in a particular land use, on a scale from 0 (no remaining individuals) to 1 (same abundance as the reference) and, in rare cases, to 2 (populations that thrive in human-modified landscapes). The resulting bii4africa dataset contains intactness scores representing terrestrial vertebrates (tetrapods: ±5,400 amphibians, reptiles, birds, mammals) and vascular plants (±45,000 forbs, graminoids, trees, shrubs) in sub-Saharan Africa across the region’s major land uses (urban, cropland, rangeland, plantation, protected, etc.) and intensities (e.g., large-scale vs smallholder cropland). This dataset was co-produced as part of the Biodiversity Intactness Index for Africa Project. Additional uses include assessing ecosystem condition; rectifying geographic/ taxonomic biases in global biodiversity indicators and maps; and informing the Red List of Ecosystems

Exploring challenges to transformational leadership communication about employment equity : managing organizational change in South Africa

The purpose of this paper is to explore the management of employment equity (EE) communication at corporate level, against the background of South African societal complexities. It speculates about how the normative ideals of transformational change communication could be applied in order to bridge the apparent divide between government's current development agenda and negative societal sentiments about EE per se on the one side, and corporate transformation efforts on the other. A multiple qualitative case study design was followed for the collection of empirical evidence. Semi-structured interviews were used for data collection in each of the three case studies. This paper indicates current trends pertaining to the complexity of communicating EE in South Africa, including the strategic value of communication. It appears that internal communication does not receive as much strategic attention as external communication does. Furthermore, some key organizational leaders (involved in EE strategy implementation) view communication as a tactical tool and not a strategic means, thereby failing to appreciate either their own leadership responsibilities, or the complex nature of transformation change communication per se. These findings confirm the need for a new breed of transformational leaders who can conceptually and practically navigate the societal and corporate complexities surrounding EE communication in the management of change in South Africa. The paper stresses the complexity of transformational change communication against the background of societal and corporate reactions to EE in South Africa.This paper is based, in part, on two papers delivered during the 2nd world Public Relations Festival in Trieste, Italy (June 27-30, 2005) and the 12th Annual International Public Relations Research Symposium, Lake Bled, Slovenia (July 1-3, 2005), respectively

Communicating affirmative action in three South African organizations : a comparative case study perspective

Problems associated with the management of communication (in the broadest sense of the word) are a recurring theme in both Corporate Communication Management and Human Resource Management literature and in research on the implementation of affirmative action as part of the Employment Equity Act in the South African context. Therefore, the following research question was formulated: "How do South African organisations manage communication about affirmative action (against the backdrop of employment equity)?". This article provides an overview of some dimensions of an exploratory qualitative study that investigated this research question. The ever-increasing strategic importance of organisational performance regarding the EEA highlights the need for research in this area. This study is one of only a few empirical studies in the field of Corporate Communication with the emphasis on topics related to the management of communication in this specific transformational context. Since this study focused on aspects that had not been researched previously (or verified empirically), an exploratory approach had to be followed, with the purpose of gauging possible current trends related to the management of communication about AA in a selection of South African organisations. A case study comparison of three organisations yielded the following results on four sub-questions derived from the overarching research question. The organisations researched (1) comply with their legal duty to inform and consult with stakeholders about the process of EE as stipulated in the Code of Good Practice for the EEA (Department of Labour, 1999); (2) the management of EE is viewed as a transformational change process, as opposed to a once-off incident; (3) the management of communication in this context is viewed as a critical success factor, but a disparity exists between the emphasis placed on strategic external and internal communication efforts; and (4) leaders at all hierarchical levels have different communication responsibilities in relation to this transformational process. Based on the results of this study, the major recommendation for the management of affirmative action communication pertains to the need to address the perceived gap between internal and external communication efforts. Since strategic internal communication is not only viewed as critical for the dissemination of information, but also as the vehicle through which transformation is facilitated, the value thereof should not be underestimated

Assessment of the induction of dormant ring stages in Plasmodium falciparum parasites by artemisone and artemisone entrapped in Pheroid vesicles in vitro

The in vitro antimalarial activities of artemisone and artemisone entrapped in Pheroid vesicles were compared, as was their ability to induce dormancy in Plasmodium falciparum. There was no increase in the activity of artemisone entrapped in Pheroid vesicles against multidrug-resistant P. falciparum lines. Artemisone induced the formation of dormant ring stages similar to dihydroartemisinin. Thus, the Pheroid delivery system neither improved the activity of artemisone nor prevented the induction of dormant ringsTechnology Innovation Agency and strategic funds from North-West Universit

Advances in GBA-associated Parkinson's disease: pathology, presentation and therapies

GBA mutations are to date the most common genetic risk factor for Parkinson's disease. The GBA gene encodes the lysomal hydrolase glucocerebrosidase. Whilst bi-allelic GBA mutations cause Gaucher disease, both mono- and bi-allelic mutations confer risk for Parkinson's disease. Clinically, Parkinson's disease patients with GBA mutations resemble idiopathic Parkinson's disease patients. However, these patients have a modest reduction in age-of-onset of disease and a greater incidence of cognitive decline. In some cases, GBA mutations are also responsible for familial Parkinson's disease. The accumulation of α-synuclein into Lewy bodies is the central neuropathological hallmark of Parkinson's disease. Pathologic GBA mutations reduce enzymatic function. A reduction in glucocerebrosidase function increases α-synuclein levels and propagation, which in turn inhibits glucocerebrosidase in a feed-forward cascade. This cascade is central to the neuropathology of GBA-associated Parkinson's disease. The lysosomal integral membrane protein type-2 is necessary for normal glucocerebrosidase function. Glucocerebrosidase dysfunction also increases in the accumulation of β-amyloid and amyloid-precursor protein, oxidative stress, neuronal susceptibility to metal ions, microglial and immune activation. These factors contribute to neuronal death. The Mendelian Parkinson's disease genes, Parkin and ATP13A2, intersect with glucocerebrosidase. These factors sketch a complex circuit of GBA-associated neuropathology. To clinically interfere with this circuit, central glucocerebrosidase function must be improved. Strategies based on reducing breakdown of mutant glucocerebrosidase and increasing the fraction that reaches the lysosome has shown promise. Breakdown can be reduced by interfering with the ability of heat-shock proteins to recognize mutant glucocerebrosidase. This underlies the therapeutic efficacy of certain pharmacological chaperones and histone deacetylase inhibitors. These therapies are promising for Parkinson's disease, regardless of mutation status. Recently, there has been a boom in studies investigating the role of glucocerebrosidase in the pathology of Parkinson's disease. This merits a comprehensive review of the current cell biological processes and pathological pictures involving Parkinson's disease associated with GBA mutation