The scientific evidence required to make policy decisions that protect human health can be challenging to organize. Primary research is often silo-ed between different agency repositories, the pace of publication is unflagging and wide-spread interdisciplinary collaboration can be logistically difficult. Since 2012, the Organisation for Economic Co-operation and Development (OECD) adverse outcome pathway (AOP) framework has provided solutions for some of the challenges of supplying relevant and accessible scientific data for evidence-based decision-making. Development of AOPs is guided by a crowd-sourced approach in which progressions of adverse outcomes (AO) are distilled into pathways containing only the essential key events (KEs) and the causal key event relationships (KERs) that connect them. The framework has widely been adopted in the toxicology community and more recently projects have applied it to the radiation safety field. Presently, a collaborative effort aims to further expand the use of AOPs through creating a network linking exposure to the space exposome with resulting human health outcomes. The network contains four adverse non-cancer outcomes for which participants of future long-range space missions will be at risk. The work of this thesis has contributed to the construction of the space-health AOP network by accomplishing two main objectives. The first was the creation of a novel protocol for collecting a weight of evidence (WOE) that included the benefits of scoping review and artificial intelligence (AI) tools for literature screening. The scoping review WOE collection strategy was then deployed for collecting data across all four outcomes in the space-health network. The second objective was to identify KEs and KERs and summarize the WOE linking space exposure to one of the four AOs: vascular remodeling. In addition to summarizing the pathway, we have also highlighted important modulating factors and knowledge gaps in the WOE. This thesis work contributes to the future of the AOP framework by formulating a new development protocol and employing it in a novel regulatory context. Using the new protocol, this thesis has furthered biological understanding of the effects of space exposure on the cardiovascular system by collating mechanistic information across scientific disciplines to identify KEs and KERs in occurrence of vascular remodeling.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/44402 |
| Date | 19 December 2022 |
| Creators | Kozbenko, Tatiana |
| Contributors | Yauk, Carole |
| Publisher | Université d'Ottawa / University of Ottawa |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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