Browsing by Subject "networks"

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    Open Access
    A reappraisal of the roles and relationships of neighbourhood watches: an investigation of selected neighbourhood watches in the Athlone and Annenberg areas in Cape Town
    (2024) Davis, Brandon; Kinnes, Irvin; Mguzulwa, Sisanda
    The Neighbourhood Watch (NW) is a pervasive phenomenon that has gained footholds in many countries around the world. South Africa is no exception and, in the case of Cape Town in the Western Cape Province, they have proven to be a popular choice among the members of civil society as a method of dealing with crime. In the Cape Flats region of Cape Town, conventional state policing agencies (namely SAPS) have failed to deal with the high rates of crime – one of the reasons for the popularity of NWs. Civil policing structures are by no means a new phenomenon in South Africa, and the concept of the NW has been in existence for decades, yet not much academic research has focused on their evolution over the years – particularly those that exist in the Cape Flats region. Using a nodal governance framework, specifically that of nodal policing, this dissertation explores the evolution of their roles, and the relationships or networks they formed (or lack thereof) over time in the battle to reduce crime and to create safe and secure communities. Indeed, numerous studies have been conducted on policing in South Africa for many decades, and some have focused on non-state policing structures in the country. In doing so, they have briefly discussed NWs, however there are few comprehensive studies that have focused solely on the NW and discussed how they have evolved over time. This study addresses that particular gap in the literature. A qualitative study was conducted and members of three different NWs on the Cape Flats located in different areas (two from the Athlone precinct and one from the Manenberg precinct) were interviewed in three separate focus group interviews. The NWs selected for this study were the Bridgetown and Silvertown NWs (Athlone precinct) and the Surrey Estate NW (Manenberg precinct). Importantly, a precinct is a defined district or region of a city which consists of multiple areas (South African National Treasury, 2014:np).
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    Open Access
    Investigating the multifaceted host contribution to COVID-19 disease risk, progression and treatment: an integrative multi-omics network-based approach study
    (2024) Agamah, Francis Adem; Martin, Darrin P; Skelton, Michelle
    Coronavirus Disease-2019 (COVID-19) is a contagious respiratory disorder caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a newly emerged β coronavirus belonging to the Coronaviridae family. Since its discovery in Wuhan, China, in December 2019, COVID-19 disease has transformed into a devastating global pandemic that has created disruptions across healthcare, economic, and social systems with approximately seven hundred and seventy million reported cases and close to seven million reported deaths as of January 2024. The clinical presentation of COVID-19 is very heterogeneous, ranging from mild disease states to severe disease states, associated with varying transcription, protein expression, lipid synthesis, and metabolic profiles. As a result of the heterogeneity of COVID-19 disease, the efficacy of drugs used to treat it may vary depending on the disease states when the medicines are administered. Molecular biology studies investigating COVID-19 clinical heterogeneity and the drugs that might be used to treat the disease have varied in terms of the approaches implemented. These approaches have focused on single features of SARS-CoV-2 infected cells such as gene transcription levels or protein expression levels (so-called “single omics” approaches) to approaches that attempt to simultaneously examine multiple molecular features of infected cells (so-called “multi-omics approaches”). This project adopts the latter approach, implementing a network-based method that integrates multi-omics data and drug-related data to investigate the contribution of host physiology to COVID-19 disease progression and identify promising drug repurposing candidates as potential treatment options. This involved evaluating existing computational integrative multi-omics network-based methods, determining their strengths and limitations, and adapting them to fit the aims of this project: identifying and characterizing biosignatures associated with various COVID-19 disease phases, as well as identifying drug repurposing candidates tailored for mild, moderate, and severe COVID-19 disease phases. The World Health Organization (WHO) Ordinal Scale (WOS) was used as a disease severity reference to harmonize COVID-19 patient metadata across two studies. A unified COVID-19 knowledge graph was constructed by assembling a disease-specific interactome from the literature and databases. We leveraged a multi-omics network-based approach to construct disease-state and omics-specific graphs by integrating proteomics, transcriptomics, metabolomics, and lipidomics data with the unified COVID-19 knowledge graph. We used an adapted random walk with restart algorithm, called multiXrank, to explore the disease-state and omics-specific graphs, and drug data to search for and prioritize not only biosignatures associated with COVID-19 disease phases but also drug candidates with the potential for treating mild, moderate, and severe COVID-19. The network analysis identified critical biosignatures for each COVID-19 phase. Mild cases displayed unique signatures like CCL4 and IRF1, potentially driving chemotaxis and interferon signaling. The moderate phase was characterized by biosignatures like HGF, MMP12, IL-10, and NFKB1, implicating enhanced inflammation, matrix remodeling, and immune regulation. In severe cases, biosignatures such as lysophosphatidylcholines, diglyceride, and sphingomyelin appeared, suggesting profound tissue damage, dysregulated lipid metabolism, and disrupted repair pathways. As expected, the abundance of shared chemokine and cytokine biosignatures in severe and moderate COVID-19 disease phases as compared to either mild vs moderate or mild vs severe disease phases suggests a closer molecular relatedness between these phases. This finding, along with biosignatures that discriminate between the disease states, and interactions between biosignatures that are either common between or associated with COVID-19 disease phases sheds light on the nuanced progression of the illness. We further investigated the differential influence of interleukin-6 (IL6) and interleukin 6 receptor (IL6R) on disease progression. We found that IL6 interaction with features of different omics data types increased with disease severity, thus indicating the differential association of IL6 with the different disease states. More specifically, IL6 interaction with proteins (e.g., IFNB, IFIT3), transcripts (e.g., CXCL1, CXCL2, CCL3), and metabolites (e.g., 1-(1-enyl-palmitoyl)-GPC, 1-(1-enyl-palmitoyl)-2-oleoyl-GPC (P-16:0/18:1)) may contribute to its major role in disease severity. We also observed that IL6R interactions mainly with proteins and transcripts increase more clearly with disease severity than do interactions with metabolites and lipids. We present a multilayered visualization tool (hosted at http://cytoscape.h3africa.org, last accessed on February 6, 2024) to navigate and analyze complex interactions across different biological layers, offering a valuable resource for uncovering key drivers of disease severity. Interestingly, cross-layer interactions between different omics profiles increased with disease severity. These potential association patterns could be useful for providing insights into the underlying molecular causes and consequences of the clinical heterogeneity of COVID-19, enabling early disease diagnosis, and optimal treatment prediction. The network-based integration of drug data and multi-omics data assisted in drug prediction. Most importantly, we prioritized twenty Food and Drug Administration approved agents with potential utility for mild, moderate, and severe COVID-19 disease phases. For mild COVID-19, stimulating immune cell recruitment and activation is key. Drugs like histamine, curcumin, and paclitaxel show potential in this regard due to their ability to stimulate immune cell recruitment, potentially mitigating disease progression. Similarly, non-steroidal anti-inflammatory drugs like indomethacin and diclofenac may offer symptomatic relief in mild cases. In mild to moderate COVID-19, drugs like omacetaxine, crizotinib, and vorinostat, known for their antiviral properties, can potentially hinder viral replication and offer additional treatment options. Moreover, glutathione, a potent antioxidant, could be valuable in moderate cases due to its potential to counteract inflammation and potentially prevent the dangerous "cytokine storm" seen in patients with antioxidant deficiencies. In severe COVID-19, the excessive immune response triggers a dangerous "inflammatory cascade." To combat this, drugs with strong anti-inflammatory effects, including anti-inflammatory drugs (sarilumab, tocilizumab), corticosteroids (dexamethasone, hydrocortisone), and immunosuppressives (sirolimus, cyclosporine), emerge as potential candidates for controlling this harmful process. Moreover, we further explore the interactions involving the drug repurposing candidates and key biosignatures. The findings could be useful for personalized treatment options tailored to individual patients based on their disease severity level. This project identified both biosignatures of different omics types (proteins, transcripts, metabolites, and lipids) enriched in disease-state pathways and their associated interactions that are either common between, or unique to mild, moderate, and severe COVID-19. These biosignatures include molecular features that underlie the observed clinical heterogeneity of COVID-19 and emphasize the need for disease-phase-specific treatment strategies. In addition, we explored the potential of multi-omics and drug-related data to predict therapeutics for different phases of COVID-19. This project demonstrates that the integrative analysis of drug data and multi-omics data enables the prioritization of biosignatures and potential drug candidates for COVID-19 disease phases. These findings hold promise for guiding future experimental studies towards potential clinical applications, requiring further investigation to definitively translate into therapeutic advancements.
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    Open Access
    Knowledge management practices and challenges in international networked NGOs: the case of one world international
    (Academic Conferences Ltd., 2008) Smith, Gretchen J; Lumba, Patricia Mweene
    This paper is based on the outcomes of a study that explored the knowledge management practices and challenges in an international NGO network. The investigation constituted comparative case studies of two centres (one in Zambia and the other in the Netherlands) belonging to a single international network. An empirically grounded framework of knowledge management practices based on the taxonomy proposed by Holsapple and Joshi was utilised as the reference framework for the study. The framework provided guidelines to characterize factors that influence organizational knowledge management; knowledge manipulation activities (processes) and organizational knowledge resources. The results of the empirical study confirm that a variety of factors affect knowledge management behaviours in an organization. These factors include managerial and internal controls such as management styles and incentives for knowledge creation and sharing; resource influences; and environmental influences relating to an organization's culture and the needs of partner organizations. The study highlights important variation in diversity, gaps and perceptions in managing knowledge between centres in the network that are based in Europe and Africa. This is despite significant communality in knowledge management processes and infrastructures. The results further show that institutionalization of knowledge management practices within a network seem to enable or constrain knowledge management at centre and network level. Recommendations are proposed to improve knowledge management practices at local and international level and include enhanced technical and advisory services at international level; capacity building; creating greater awareness of knowledge management; decentralization of knowledge management processes; implementation of a knowledge management strategy at network level and improving relationships between centres. The authors conclude that networked NGO's and specifically OWI could operate more efficiently and incrementally enhance service provision by leveraging their knowledge resources more effectively. It is in this light that knowledge management practices should be examined in NGOs and particularly networks with their complex structures and attendant reoccurring and unavoidable problems.