Task CNS Damage Signaling Neuropathology – Modeling Supplement
Last Published:  07/30/21 01:05:34 PM (Central)
Short Title: CBS CNS Damage Signaling Neuropathology – Modeling Supplement (Wyrobek)
Responsible HRP Element: Human Factors and Behavioral Performance
Collaborating Org(s):
Human Factors and Behavioral Performance (HFBP) Element
Human Health Countermeasures (HHC) Element
Space Radiation (SR) Element
Funding Status: Active - Currently funded and in progress
Procurement Mechanism(s):
Directed
Supplement
Aims:

Aim 1. Characterize and build computational models for the effects of age-at-exposure and dose fractionation (repeated exposures) on performance in each of three behavioral domains, using NASA-provided data sets.

 

  • Aim 1a. Evaluate the age-at-exposure and dose fractionation data sets for data quality across ions, exposure regimens, study design, and behavioral outcomes, and for suitability for multivariate modeling of risks for specific behavioral domains.

 

  • Aim 1b. Build single-ion risk models that incorporate age-at-exposure and dose-fractionation effects for each behavioral domain, using data sets that pass the Aim 1a evaluation criteria.

 

  • Aim 1c. Build multi-ion risk models that integrate the age-at-exposure and dose-fractionation effects for each behavioral domain from the single ion models of Aim 1b. The risk predictions of the different behavioral domains will be evaluated using both experimental exposure regimens and GCR-relevant estimates for ion spectra and doses.

 

Aim 2. Characterize and build computational models for exposure dose and effect modifiers of performance in three behavioral domains, using NASA-provided data sets.

 

  • Aim 2a. Evaluate the dose-response and effect-modifier data sets for data quality across ions, exposure regimens, study design, and behavioral outcomes, and for suitability for multivariate modeling of risks for specific behavioral domains. Effect modifiers to be assessed may include strain/genotype, sex, and diet group, depending on the data sets provided.

 

  • Aim 2b. Build single-ion risk models that incorporate dose-response and effect-modifier effects for each behavioral domain, using data sets that pass the Aim 2a evaluation criteria.

 

  • Aim 2c. Build multi-ion risk models that incorporate dose-response and effect-modifier effects for each behavioral domain, based on the findings of the single ion models of Aim 2b. The risk predictions of the different behavioral domains will be evaluated using both experimental exposure regimens and GCR-relevant estimates for ion spectra and doses.

 

Aim 3. Apply advanced statistical methods to integrate the risk estimates from Aim 1 and Aim 2 into a unified model to predict individual-level risk for specific behavioral domains.

 

Aim 4. Evaluate NASA-provided data sets for building computational models for associations of

CNS tissue biomarkers with performance in three behavioral domains.

 

  • Aim 4a. Evaluate the CNS tissue biomarker and behavioral outcomes data set for data quality across exposure regimens and behavioral outcomes, and for suitability for multivariate modeling of risks for specific behavioral domains. Effect modifiers that maybe available include strain/genotype and age at exposure. The data sets expected to be available for aim 4 are likely to be single ion experiments with molecular biomarker data from a few CNS sub-regions in animals tested for behavioral outcomes.

 

  • Aim 4b. Build single-ion risk models for CNS tissue biomarkers for each behavioral domain, using data sets that pass the Aim 4a evaluation criteria
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