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Ontology-based Semantic Harmonization of HIV-associated Common Data Elements for Integration of Diverse HIV Research DatasetsBrown III, William January 2016 (has links)
Analysis of integrated, diverse, Human Immunodeficiency Virus (HIV)-associated datasets can increase knowledge and guide the development of novel and effective interventions for disease prevention and treatment by increasing breadth of variables and statistical power, particularly for sub-group analyses. This topic has been identified as a National Institutes of Health research priority, but few efforts have been made to integrate data across HIV studies. Our aims were to: 1) Characterize the semantic heterogeneity (SH) in the HIV research domain; 2) Identify HIV-associated common data elements (CDEs) in empirically generated and knowledge-based resources; 3) Create a formal representation of HIV-associated CDEs in the form of an HIV-associated Entities in Research Ontology (HERO); 4) Assess the feasibility of using HERO to semantically harmonize HIV research data. Our approach was guided by information/knowledge theory and the DIKW (Data Information Knowledge Wisdom) hierarchical model.
Our systematized review of the literature revealed that synergistic use of both ontologies and CDEs included integration, interoperability, data exchange, and data standardization. Moreover, methods and tools included use of experts for CDE identification, the Unified Medical Language System, natural language processing, Extensible Markup Language, Health Level 7, and ontology development tools (e.g., Protégé). Additionally, evaluation methods included expert assessment, quantification of mapping tasks between raters, assessment of interrater reliability, and comparison to established standards. We used these findings to inform our process for achieving the study aims.
For Aim 1, we analyzed eight disparate HIV-associated data dictionaries and developed a String Metric-assisted Assessment of Semantic Heterogeneity (SMASH) method, which aided identification of 127 (13%) homogeneous data element (DE) pairs and 1,048 (87%) semantically heterogeneous DE pairs. Most heterogeneous pairs (97%) were semantically-equivalent/syntactically-different, allowing us to determine that SH in the HIV research domain was high.
To achieve Aim 2, we used Clinicaltrials.gov, Google Search, and text mining in R to identify HIV-associated CDEs in HIV journal articles, HIV-associated datasets, AIDSinfo HIV/AIDS Glossary, AIDSinfo Drug Database, Logical Observation Identifiers Names and Codes (LOINC), Systematized Nomenclature of Medicine (SNOMED), and RxNORM (understood as prescription normalization). Two HIV experts then manually reviewed DEs from the journal articles and data dictionaries to confirm DE commonality and resolved semantic discrepancies through discussion. Ultimately, we identified 2,179 unique CDEs. Of all CDEs, data-driven approaches identified 2,055 (94%) (999 from the HIV/AIDS Glossary, 398 from the Drug Database, 91 from journal articles, and a total of 567 from LOINC, SNOMED, and RxNorm cumulatively). Expert-based approaches identified 124 (6%) unique CDEs from data dictionaries and confirmed the 91 CDEs from journal articles.
In Aim 3, we used the Protégé suite of ontology development tools and the 2,179 CDEs to develop the HERO. We modeled the ontology using the semantic structure of the Medical Entities Dictionary, available hierarchical information from the CDE knowledge resources, and expert knowledge. The ontology fulfilled most relevant criteria from Cimino’s desiderata and OntoClean ontology engineering principles, and it successfully answered eight competency questions.
Finally, for Aim 4, we assessed the feasibility of using HERO to semantically harmonize and integrate the data dictionaries from two diverse HIV-associated datasets. Two HIV experts involved in the development of HERO independently assessed each data dictionary. Of the 367 DEs in data dictionary 1 (D1), 181 (49.32%) were identified as CDEs and 186 (50.68%) were not CDEs, and of the 72 DEs in data dictionary 2 (D2), 37 (51.39%) were CDEs and 35 (48.61%) were not CDEs. The HIV experts then traversed HERO’s hierarchy to map CDEs from D1 and D2 to CDEs in HERO. Of the 181 CDEs in D1, 156 (86.19%) were found in HERO, and 25 (13.81%) were not. Similarly, of the 37 CDEs in D2 32 (86.48%) were found in HERO, and 5 (13.51%) were not. Interrater reliability for CDE identification as measured by Cohen’s Kappa was 0.900 for D1 and 0.892 for D2. Cohen’s Kappas for CDEs in D1 and D2 that were also identified in HERO were 0.885 and 0.688, respectively.
Subsequently, to demonstrate the integration of the two HIV-associated datasets, a sample of semantically harmonized CDEs in both datasets was categorically selected (e.g. administrative, demographic, and behavioral), and D2 sample size increases were calculated for race (e.g., White, African American/Black, Asian/Pacific Islander, Native American/Indian, and Hispanic/Latino) and for “intravenous drug use” from the integrated datasets. The average increase of D2 CDEs for six selected CDEs was 1,928%.
Despite the limitation of HERO developers also serving as evaluators, the contributions of the study to the fields of informatics and HIV research were substantial. Confirmatory contributions include: identification of effective CDE/ontology tools, and use of data-driven and expert-based methods. Novel contributions include: development of SMASH and HERO; and new contributions include documenting that SH is high in HIV-associated datasets, identifying 2,179 HIV-associated CDEs, creating two additional classifications of SH, and showing that using HERO for semantic harmonization of HIV-associated data dictionaries is feasible. Our future work will build upon this research by expanding the numbers and types of datasets, refining our methods and tools, and conducting an external evaluation.
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Exploring research participant's perceptions and comprehension of the informed consent process in a pre-exposure HIV prevention study in Zimbabwe : a case study.Ruzariro, Sithembile. January 2012 (has links)
Background. An inherent challenge in HIV prevention studies is making sure that trial participants
understand the information. This study explored trial participants’ perceptions and
comprehension of the informed consent process in a pre-exposure HIV prevention
study. Method. Face-to-face in-depth interviews, using a study guide, were held with twenty
interviewees purposively selected from ex-participants of an HIV prevention study.
Audio-recorded data were transcribed, translated, coded using NVivo 8, and analysed
according to themes. Results. The participants were all women between the ages of 18 and 40. Participants felt that
key information had been given during the informed consent process. Most felt that the
process of obtaining informed consent was rushed with some participants citing a need
for more time to make a decision regarding participation. Some participants felt
pressured to sign consent forms. Some found it difficult to ask questions and mixed
feelings existed on male partner involvement in the decision-making process.
Conclusions: Participants experienced the consent process as rushed and most only fully
comprehended study concepts with time. Their concerns necessitate the reassessment
of informed consent processes in a developing world setting. / Thesis (M.Soc.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2012.
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HIV Biomedical Prevention Science and the Business of Gender and Sexual DiversityPerez-Brumer, Amaya Gabriela January 2019 (has links)
This dissertation examines the political economy of HIV biomedical prevention research—largely designed in the global North but conducted in the global South—and its implications for people of diverse genders and sexualities. As a recognized global leader in HIV biomedical prevention research among people categorized as men who have sex with men (MSM) and transgender women, Peru offers a key site in which to explore the increasing focus on gender and sexual identity as a strategic area for extractive research practices. This phenomenon has become particularly visible in the epidemic’s 4th decade, which has emphasized the pursuit of biomedical prevention strategies. Building on nine years of previous experience working inside HIV biomedical prevention studies, this project involved 24 months of ethnographic research, including participant observation; 110 interviews with scientists, study staff, and research subjects; 10 focus groups; and analyses of relevant scientific publications.
This study presents four key findings. First, US and Peruvian researchers’ historical and continued entanglement primed Peru to become a hotbed of HIV biomedical prevention research. In this context, population categories imported from the global North have served as powerful tools to sustain a booming local research market, which produces data that aligns with the global demands of the HIV industry. Second, on the ground, research begets more research rather than institutionalized HIV prevention technologies, creating a sustained enterprise in which issues of compensation, value, and labor shape the science. The commodification of gender and sexually diverse identities operates here in two ways: as a mechanism to access particular kinds of bodies and associated HIV risk data, and as a mechanism by which to claim expertise in the HIV prevention research industry for both researchers and community members. Third, Peruvians classified as MSM and transgender women are afforded only temporary access to cutting-edge strategies to prevent HIV, limited to study participation. The result is a sustained pool of people in need of HIV care primed to support the HIV biomedical research economy. Finally, this project illuminates a key paradox within the industry’s contemporary focus on gender and sexual diversity in HIV prevention science. This focus creates the impression that progressive health politics marked the field, while obscuring and absolving ongoing forms of exploitation and unequal gains embedded within it.
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Cultural conceptions of research and informed consent.Gasa, Nolwazi Bright Khanyisile. January 1999 (has links)
AIDS has had a negative impact on developing countries. Because most developing countries
cannot afford the new antiretroviral drug therapies, it has been suggested that preventive
vaccines might reduce the spread of the HIV/AIDS epidemic (Bloom, 1998). The clinical
trials of AIDS vaccines do, however, present with complex ethical issues such as informed
consent. Informed consent is primarily grounded on the Western principle of respect for
individuals as autonomous agents. This may be at variance, however, with African societies'
emphasis on the social embeddedness of the individual.
The current study forms part of the HIVNET vaccine trials to be conducted in Hlabisa, in
Northern Zululand, under the auspices of the South African Medical Research Council. The
main aim of the study was to explore key informants' cultural conceptions of research and
informed consent in order to facilitate community consultation and cultural sensitivity.
Maximum variation sampling was used to select twenty-three key informants, who are in
leadership positions within Hlabisa. An interview guide was used to facilitate narrative
disclosure of cultural conceptions of research and informed consent. Perceptions of research,
conceptions of the informed consent process, and projected motivations for why individuals
agree to participate in studies were explored during interviews.
Results suggest that members of the Hlabisa community have a limited understanding of the
Western research process. Community education about research is therefore warranted.
Informants indicated that community members would value the establishment of a
relationship characterised by mutual respect for cultural differences between researchers and
participants. This was perceived as likely to facilitate shared decision-making, and the
reduction of the power differentials that exist between researchers and participants. While the
involvement of key community leaders and family members was recommended by most
informants, a few informants felt that participants could also make individual decisions about
participation. The theoretical implications of the study are considered last. / Thesis (M.A.)-University of Natal, Pietermaritzburg, 1999.
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South African stakeholders' perceptions of informed consent in HIV vaccine trials.Brindley-Richards, Lenna Getrinna. January 2008 (has links)
In the history of public health vaccines have proven to be among the most effective disease prevention tools. It is clear that in the fight against HIV that new and powerful preventive technology such as a vaccine is badly needed. Ethically, however the processes of developing a vaccine against HIV have been distinctly different from that of any previous pharmaceutical products. HIV vaccine trials can be ethically complex for a number of reasons. In 2004 the HIV I AIDS Vaccine Ethics Group undertook a research initiative that aimed to collect data from various South African stake holders of HIV vaccine trials to ascertain what they perceived as the ethical challenges related to HIV vaccine trials. A quantitative content analysis on the data from 31 semistructured interviews revealed that the ethical issue listed spontaneously by most of the respondents was that of informed consent. Further probing and discussion on informed consent identified a number of sub issues which the respondents thought would pose important challenges to HIV vaccine trials in the South African context. This study undertook to do a more in-depth qualitative analysis of the data to ascertain whether the challenges and concerns the stakeholders have are consistent with or different to those already identified in the literature and ethical guidelines on informed consent in medical research. What variables may be impacting on the position stakeholders take was also of interest. Results indicated that many concerns relating to the substantive and procedural elements of informed consent were consistent with those debated in the literature. These issues related to first person consent, the voluntariness of participants' consent, practicing cultural sensitivity, dealing with language issues, promoting and assessing understanding of material disclosed, issues around the vulnerability of .. participants, children and adolescents' capacity to consent and the role of the media. More specific to the South African context, stakeholders were concerned about the legal framework under which the trials take place, the general lack of education and training about HIV vaccine trials, a lack of communication and coordination between stakeholder groups, and the historical influences of apartheid on black South African participants' capacity to consent. The main variables that appeared to impact on the position stakeholders took related to the role the stakeholders play within the trials, the philosophical position underpinning their ethical viewpoints, stakeholders' understanding of vulnerability and capacity to consent, and how they view the universality or relativity of ethical issues. / Thesis (M.A.)-University of KwaZulu-Natal, Pietermaritzburg, 2008.
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Developing a strategy for a centre of competence for HIV research and development in South AfricaMontague, Carl Thomas 12 1900 (has links)
Thesis (MBA (Business Management))--Stellenbosch University, 2008. / The government has identified the need to transform the South African economy from one that is primarily resource based to one that is knowledge-based and has formulated a 10 year plan in order to accomplish this objective. The plan involves the creation and funding of five theme-specific consortium-based centres of competence that focus on the five top national health priorities, linked to the growth of the local pharmaceutical industry. This research study proposed that if collaboration and communication between academic researchers and the biotechnology industry in South Africa was improved it would lead to an increase in the development of innovative products for HIV/AIDS prevention and treatment. The objective of the study was the development of a strategy for a centre of competence for HIV research and development that brings together academic researchers and industry in a public private partnership and that will enable the proposal to be tested.
Centre of competence programmes in both developed and developing countries, including Sweden, Austria and Estonia, were reviewed. The success factors for the various programmes were discussed.
The strategic planning analysis began by considering the mandate of the CoC for HIV R&D. The requirements and expectations of the DST in establishment of the centres of competence were examined. An analysis of the external environment relevant to the South African biotechnology industry was then performed. This involved a detailed macro-environmental analysis in which political, economic, social, technological and environmental factors were considered. It was followed by an analysis of the current biotechnology industry in South Africa. The industry’s dominant economic features were identified as were its future driving forces. In a competitive environment analysis the South African biotechnology industry was found to be extremely competitive. Two industry issues, price controls and access to capital, were identified and discussed. The industry key success factors identified included access to large and sustained capital, attracting and retaining talented employees, an efficient and high quality regulatory authority, continued government support, productive and appropriate partnerships and skilled intellectual property management.
An internal environment analysis was performed which identified competencies and resource strengths of the CoC for HIV R&D, including the high level of academic research in the HIV/AIDS field and expertise in clinical trials of HIV/AIDS products. Competitive deficiencies and resource weaknesses identified included shortages of skills and talent and the lack of co-ordination for funding of HIV/AIDS research. The analysis of the internal environment continued with the examination of the internal value chain of the CoC for HIV R&D. This consisted of discovery, pre-clinical development and clinical development stages. Gaps in the value chain were identified, including the lack of facilities for high-throughput screening of compounds for anti-HIV activity, lack of pre-clinical testing facilities and lack of manufacturing plants capable of producing products for use in clinical trials.
The results of the external and internal environment analysis were used in a SWOC analysis and a number of strategies were identified to capitalise on opportunities and to address challenges. A subsequent competitive strength assessment identified a competitive advantage in the formation of the CoC for HIV R&D. In addition a number of strategic issues facing the centre were identified and ways to address or manage the issues were proposed.
The strategic planning process was completed by the selection of a strategic approach for the CoC for HIV R&D. The study concluded that a PPP of public and private organisations operating under a corporate strategy of related diversification developed and implemented by the CoC for HIV R&D, would be suitable for testing the Proposal.
The study’s conclusion also highlighted the need to ensure that the CoC for HIV R&D receives a long term commitment of funding from public sources, and that is managed by an experienced team with strong leadership skills.
Important strategies emerging from the study and specifically from the SWOC analysis were development of a national HIV research plan and funding of the highest priority projects; focusing research funding on research with greatest potential for generation of HIV/AIDS products; and establishment of new technology platforms to fill gaps in the value chain.
Finally, a number of recommendations were made for implementation of the results of this study or as the basis for further study.
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On modelling the transmission of the Human Immunodeficiency Virus (HIV) in a closed mixed societyMudimu, Edinah 06 1900 (has links)
This thesis sought to develop an agent-based model that replicates the formation of social and sexual partnerships in real-world settings with an eventual aim of revealing the main drivers of the HIV pandemic
in a closed mixed society. Agent-based modelling is a computational modelling approach that allows for the simulation of the actions and interactions of autonomous agents, with the eventual objective of disovering global effects on the system. This modelling technique is less dependent on generalisations and does not average out the behaviour of individuals. Sexual partnerships formed in the model goes through the process of dating, courting and has a chance of developing into marriage as well as the possibility of breaking up or undergo divorce. Sexual partnership formation is based on a likeability index calculated using aspiration, attractiveness and age. Over and above the the sexual relationships we include commercial sex work. Commercial sex work depends mainly on the availability of female sex workers and their clients. We superimpose the spread of HIV on the social and sexual network model. Results from the model reveal that saturation of HIV prevalence is driven by the social and sexual network structure, behaviour change as well as biologic factors. Excluding commercial sex work in the model resulted in a decrease in HIV prevalence and incidence. Dense social networks resulted in a dense sexual network which consequently increased HIV incidence. A change in the infection probability per coital act contributed significantly to a change in incidence and prevalence levels. Model results also show that enrolling all HIV positive agents on antiretroviral therapy (ART) as from 2016 simulation year will help in curbing
HIV transmission if zero dropout rate from ART is assumed. Therefore, on concomitant action to avoid dropouts from ART is necessary if full benefits of introducing ART to all HIV positive individuals are to be realised. / Operations Management / D.Phil. (Operations Research)
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Transfer of intracellular HIV Nef to endothelium causes endothelial dysfunctionWang, Ting January 2014 (has links)
Indiana University-Purdue University Indianapolis (IUPUI) / With effective antiretroviral therapy (ART), cardiovascular diseases (CVD), are emerging as a major cause of morbidity and death in the aging population with HIV infection. Although this increase in CVD could be partially explained by the toxic effects of combined anti-retroviral therapy (ART), more recently, HIV infection has emerged as an independent risk factor for CVD. However, it is unclear how HIV can contribute to CVD in patients on ART, when viral titers are low or non-detectable. Here, we provide several lines of evidence that HIV-Nef, produced in infected cells even when virus production is halted by ART, can lead to endothelial activation and dysfunction, and thus may be involved in CVD. We demonstrate that HIV-infected T cell-induced endothelial cell activation requires direct contact as well as functional HIV-Nef. Nef protein from either HIV-infected or Nef-transfected T cells rapidly transfers to endothelial cells while inducing nanotube-like conduits connecting T cells to endothelial cells. This transfer or transfection of endothelial cells results in endothelial apoptosis, ROS generation and release of monocyte attractant protein-1 (MCP-1). A Nef SH3 binding site mutant abolishes Nef-induced apoptosis and ROS formation and reduces MCP-1 production in endothelial cells, suggesting that the Nef SH3 binding site is critical for Nef effects on endothelial cells. Nef induces apoptosis of endothelial cells through both NADPH oxidase- and ROS-dependent mechanisms, while Nef-induced MCP-1 production is NF-kB dependent. Importantly, Nef can be found in CD4 positive and bystander circulating blood cells in patients receiving virally suppressive ART, and in the endothelium of chimeric SIV-infected macaques. Together, these data indicate that Nef could exert pro-atherogenic effects on the endothelium even when HIV infection is controlled and that inhibition of Nef-associated pathways may be promising new therapeutic targets for reducing the risk for cardiovascular disease in the HIV-infected population.
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