Enhancing Interdisciplinary Human System Risk Research Through Modeling and Network Approaches

NASA's Human Research Program (HRP) supports research to reduce human health and performance risks inherent in future human space exploration missions. Understanding risk outcomes and contributing factors in an integrated manner allows HRP research to support development of efficient and effective mitigations from crossdisciplinary perspectives, and to enable resilient human and engineered systems for spaceflight. The purpose of this work is to support scientific collaborations and research portfolio management by utilizing modeling for analysis and visualization of current and potential future interdisciplinary efforts

Space radiation-induced bystander signaling in 2D and 3D skin tissue models

Thesis (Sc. D.)--Harvard-MIT Program in Health Sciences and Technology, 2012.Page 157 blank. Cataloged from PDF version of thesis.Includes bibliographical references (p. 145-156).Space radiation poses a significant hazard to astronauts on long-duration missions, and the low fluences of charged particles characteristic of this field suggest that bystander effects, the phenomenon in which a greater number of cells exhibit damage than expected based on the number of cells traversed by radiation, could be significant contributors to overall cell damage. The purpose of this thesis was to investigate bystander effects due to signaling between different cell types cultured within 2D and 3D tissue architectures. 2D bystander signaling was investigated using a transwell insert system in which normal human fibroblasts (A) and keratinocytes (K) were irradiated with 1 GeV/n protons or iron ions at the NASA Space Radiation Laboratory using doses from either 2 Gy (protons) or 1 Gy (iron ions) down to spacerelevant low fluences. Medium-mediated bystander responses were investigated using three cell signaling combinations. Bystander signaling was also investigated in a 3D model by developing tissue constructs consisting of fibroblasts embedded in a collagen matrix with a keratinocyte epidermal layer. Bystander experiments were conducted by splitting each construct in half and exposing half to radiation then placing the other half in direct contact with the irradiated tissue on a transwell insert. Cell damage was evaluated primarily as formation of foci of the DNA repair-related protein 53BP1. In the 2D system, both protons and iron ions yielded a strong dose dependence for the induction of 53BP1 in irradiated cells, while the magnitudes and time courses of bystander responses were dependent on radiation quality. Furthermore, bystander effects were present in all three cell signaling combinations even at the low proton particle fluences used, suggesting the potential importance of including these effects in cancer risk models for low-dose space radiation exposures. Cells cultured in the 3D constructs exhibited a significant reduction in the percentages of both direct and bystander cells positive for 53BP1 foci, although the qualitative kinetics of DNA damage and repair were similar to those observed in 2D. These results provide evidence that the microenvironment significantly influences intercellular signaling and that cells may be more radioresistant in 3D compared to 2D systems.by Sarah B. Lumpkins.Sc.D

An Evidence Base for Human Spaceflight Risks in Wikipedia

NASA's Human Research Program (HRP) is focused on understanding and mitigating thirty two risks to crew health and performance in exploration missions beyond low Earth orbit. The HRP has developed an evidence report for each of the risks. Most evidence reports are a brief review article describing the evidence related to a specified risk, written at a level appropriate for the scientifically educated, nonspecialist reader. Each evidence report captured the current state of knowledge from both research and operations. Two limitations of the evidence reports have become apparent: 1) they are updated infrequently and 2) they do not take full advantage of the expertise available in other space agencies and in related fields of terrestrial research. Therefore, the HRP is experimenting with the use of Wikipedia articles as a repository for evidence. Wikipedia's accessibility to the international space flight community and researchers in related terrestrial fields creates the opportunity to generate a more timely and comprehensive evidence base. Initial Wikipedia articles were populated for seven risks using a subset of the information in the HRPapproved evidence reports: Fatigue and Sleep Loss, Treating An Ill or Injured Crew Member, Radiation Carcinogenesis, Visual Impairment and Intracranial Pressure, Renal Stone Formation, Team Cohesion, and Intervertebral Disc Damage. Since the initial articles were created, there have been additions to these Wikipedia articles, including content from sources outside the HRP, and editorial changes to the pages. We will report on the nature of the contributions made after the initial articles were created, the comprehensiveness of the resulting Wikipedia articles, and the effort required to maintain quality control of the content. The Wikipedia approach will also be compared to wiki efforts that exert more traditional editorial control of content prior to posting

How HRP Research Results Contribute to Human Space Exploration Risk Mitigation

In addition to the scientific value of publications derived from research, results from Human Research Program (HRP) research also support HRP's goals of mitigating crew health and performance risks in space flight. Research results are used to build the evidence base characterizing crew health and performance risks, to support risk research plan development, to inform crew health and performance standards, and to provide technologies to programs for meeting those standards and optimizing crew health and performance in space. This talk will describe examples of how research results support these efforts. For example, HRP research results are used to revise or even create new standards for human space flight, which have been established to protect crew health and performance during flight, and prevent negative long-term health consequences due to space flight. These standards are based on the best available clinical and scientific evidence, as well as operational experience from previous space flight missions, and are reviewed as new evidence emerges. Research results are also used to update the HRP evidence base, which is comprised of a set of reports that provide a current record of the state of knowledge from research and operations for each of the defined human health and performance risks for future NASA exploration missions. A discussion of the role of evidence within the HRP architecture will also be presented. The scope of HRP research results extends well beyond publications, as they are used in several capacities to support HRP deliverables and, ultimately, the advancement of human space exploration beyond low-Earth orbit

Modeling for Integrated Science Management and Resilient Systems Development

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Concepts to Support HRP Integration Using Publications and Modeling

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Multivariate Dynamical Modeling to Investigate Human Adaptation to Space Flight: Initial Concepts

The array of physiological changes that occur when humans venture into space for long periods presents a challenge to future exploration. The changes are conventionally investigated independently, but a complete understanding of adaptation requires a conceptual basis founded in intergrative physiology, aided by appropriate mathematical modeling. NASA is in the early stages of developing such an approach

Multivariate Dynamic Modeling to Investigate Human Adaptation to Space Flight: Initial Concepts

The array of physiological changes that occur when humans venture into space for long periods presents a challenge to future exploration. The changes are conventionally investigated independently, but a complete understanding of adaptation requires a conceptual basis founded in integrative physiology, aided by appropriate mathematical modeling. NASA is in the early stages of developing such an approach

Risk Interfaces to Support Integrated Systems Analysis and Development

Objectives for systems analysis capability: Develop integrated understanding of how a complex human physiological-socio-technical mission system behaves in spaceflight. Why? Support development of integrated solutions that prevent unwanted outcomes (Implementable approaches to minimize mission resources(mass, power, crew time, etc.)); Support development of tools for autonomy (need for exploration) (Assess and maintain resilience -individuals, teams, integrated system). Output of this exercise: -Representation of interfaces based on Human System Risk Board (HSRB) Risk Summary information and simple status based on Human Research Roadmap; Consolidated HSRB information applied to support communication; Point-of-Departure for HRP Element planning; Ability to track and communicate status of collaborations.

Evidence Report: Risk of Radiation Carcinogenesis

As noted by Durante and Cucinotta (2008), cancer risk caused by exposure to space radiation is now generally considered a main hindrance to interplanetary travel for the following reasons: large uncertainties are associated with the projected cancer risk estimates; no simple and effective countermeasures are available, and significant uncertainties prevent scientists from determining the effectiveness of countermeasures. Optimizing operational parameters such as the length of space missions, crew selection for age and sex, or applying mitigation measures such as radiation shielding or use of biological countermeasures can be used to reduce risk, but these procedures have inherent limitations and are clouded by uncertainties. Space radiation is comprised of high energy protons, neutrons and high charge (Z) and energy (E) nuclei (HZE). The ionization patterns and resulting biological insults of these particles in molecules, cells, and tissues are distinct from typical terrestrial radiation, which is largely X-rays and gamma-rays, and generally characterized as low linear energy transfer (LET) radiation. Galactic cosmic rays (GCR) are comprised mostly of highly energetic protons with a small component of high charge and energy (HZE) nuclei. Prominent HZE nuclei include He, C, O, Ne, Mg, Si, and Fe. GCR ions have median energies near 1 GeV/n, and energies as high as 10 GeV/n make important contributions to the total exposure. Ionizing radiation is a well known carcinogen on Earth (BEIR 2006). The risks of cancer from X-rays and gamma-rays have been established at doses above 50 mSv (5 rem), although there are important uncertainties and on-going scientific debate about cancer risk at lower doses and at low dose rates (<50 mSv/h). The relationship between the early biological effects of HZE nuclei and the probability of cancer in humans is poorly understood, and it is this missing knowledge that leads to significant uncertainties in projecting cancer risks during space exploration (Cucinotta and Durante 2006; Durante and Cucinotta 2008)