Validating Causal Diagrams of Human Health Risks for Spaceflight: An Example Using Bone Data from Rodents

Abstract

As part of the risk management plan for human system risks at the US National Aeronautics and Space Administration (NASA), the NASA Human Systems Risk Board uses causal diagrams (in the form of directed, acyclic graphs, or DAGs) to communicate the complex web of events that leads from exposure to the spaceflight environment to performance and health outcomes. However, the use of DAGs in this way is relatively new at NASA, and thus far, no method has been articulated for testing their veracity using empirical data. In this paper, we demonstrate a set of procedures for doing so, using (a) a DAG related to the risk of bone fracture after exposure to spaceflight; and (b) four datasets originally generated to investigate this phenomenon in rodents. Tests of expected marginal correlation and conditional independencies derived from the DAG indicate that the rodent data largely agree with the structure of the diagram. Incongruencies between tests and the expected relationships in one of the datasets are likely explained by inadequate representation of a key DAG variable in the dataset. Future directions include greater tie-in with human data sources, including multiomics data, which may allow for more robust characterization and measurement of DAG variables.

Addressing Spaceflight Biology through the Lens of a Histologist–Embryologist

“…Additionally, one can premise that most of the experiments are performed on larvae, crickets or amphibians that do not emulate human biology, per se. As highlighted in the current review, these model organisms have been widely employed by NASA to assess biological risks associated with space travel (e.g., the vestibular system’s adaptation performed on STS-40 (Spacelab-1), STS-58 (Spacelab-2), and STS-90 (Neurolab)) and bone formation, to capitalize on human exploration and benefit society on Earth [ 158 ]. Additionally, space medicine may sound utopian, but miniaturized organoids on chips testing drugs [ 159 ] and cancer studies have been designed under space conditions [ 160 ] already, postulating promising results.…”

Translation from Microgravity Research to Earth Application

“…The topic “Translation from Microgravity Research to Earth Application” comprises publications focusing on space life sciences, gravitational biology and space medicine [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. It covers publications reporting the impact of altered environmental conditions, such as microgravity (µ g ), cosmic radiation and isolation on organisms down to the level of cells [ 3 , 4 , 5 , 7 , 8 , 10 , 11 , 12 , 13 , 14 ].…”

“…It covers publications reporting the impact of altered environmental conditions, such as microgravity (µ g ), cosmic radiation and isolation on organisms down to the level of cells [ 3 , 4 , 5 , 7 , 8 , 10 , 11 , 12 , 13 , 14 ]. In addition, the topic collects studies validating causal diagrams of human health risks for spaceflight [ 1 ], hypergravity studies [ 2 ] and investigations about the impact of extreme isolation in the Antarctica on the human body [ 6 ].…”

“…Reynolds et al validated causal diagrams of human health risks for spaceflight and used as an example bone data from rodents [ 1 ]. They applied DAGs to determine the risk of bone fractures of rodents in space [ 1 ].…”

“…Reynolds et al validated causal diagrams of human health risks for spaceflight and used as an example bone data from rodents [ 1 ]. They applied DAGs to determine the risk of bone fractures of rodents in space [ 1 ]. Ganse et al [ 4 ] focused on comparable cartilage alterations in humans, animals and cells during spaceflight.…”