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NASA NTRS2011

CPRIT/Johnson Space Center, September, 2011 (Cancer Prevention and Research Institute of Texas)

JSC researchers study carcinogenesis, cancer prevention and treatment along with epidemiological (primarily retrospective and longitudinal) studies, modeling, and interactions with the environment such as radiation, nutritional, and endocrine changes related to space flight along with behaviors such as smoking. Cancer research is a major focus for human space flight due to the exposure to space radiation which consists of particles of varying charges and energies, and secondary neutrons. The JSC laboratories collaborate with investigators from the U.S. as well as our European and Japanese partners. We use accelerator facilities at the Brookhaven National Laboratory, Loma Linda University and Los Alamos National Laboratory that generate high energy charged particles and neutrons to simulate cosmic radiation and solar particle events. The research using cultured cells and animals concentrates on damage and repair from the level of DNA to organ tissues, due to exposure to simulated space radiation exposure, that contribute to the induction of leukemia and solid tumors in most major tissues such as lung, colon, liver and breast. The goal of the research is to develop a mathematical model that can predict cancer morbidity and mortality risks with sufficient accuracy for a given space mission.

Davis, Jeffrey↗
NASA NTRS2011

Sensitivity Analysis of Median Lifetime on Radiation Risks Estimates for Cancer and Circulatory Disease amongst Never-Smokers

Radiation risks are estimated in a competing risk formalism where age or time after exposure estimates of increased risks for cancer and circulatory diseases are folded with a probability to survive to a given age. The survival function, also called the life-table, changes with calendar year, gender, smoking status and other demographic variables. An outstanding problem in risk estimation is the method of risk transfer between exposed populations and a second population where risks are to be estimated. Approaches used to transfer risks are based on: 1) Multiplicative risk transfer models -proportional to background disease rates. 2) Additive risk transfer model -risks independent of background rates. In addition, a Mixture model is often considered where the multiplicative and additive transfer assumptions are given weighted contributions. We studied the influence of the survival probability on the risk of exposure induced cancer and circulatory disease morbidity and mortality in the Multiplicative transfer model and the Mixture model. Risks for never-smokers (NS) compared to the average U.S. population are estimated to be reduced between 30% and 60% dependent on model assumptions. Lung cancer is the major contributor to the reduction for NS, with additional contributions from circulatory diseases and cancers of the stomach, liver, bladder, oral cavity, esophagus, colon, a portion of the solid cancer remainder, and leukemia. Greater improvements in risk estimates for NS s are possible, and would be dependent on improved understanding of risk transfer models, and elucidating the role of space radiation on the various stages of disease formation (e.g. initiation, promotion, and progression).

Chappell, Lori J.↗
NASA NTRS2011

Induction of a Radio-Adaptive Response by Low-dose Gamma Irradiation in Mouse Cardiomyocytes

One of the most significant occupational hazards to an astronaut is the frequent exposure to radiation. Commonly associated with increased risk for cancer related morbidity and mortality, radiation is also known to increase the risk for cardiovascular related disorders including: pericarditis, hypertension, and heart failure. It is believed that these radiation-induced disorders are a result of abnormal tissue remodeling. It is unknown whether radiation exposure promotes remodeling through fibrotic changes alone or in combination with programmed cell death. Furthermore, it is not known whether it is possible to mitigate the hazardous effects of radiation exposure. As such, we assessed the expression and mechanisms of radiation-induced tissue remodeling and potential radio-adaptive responses of p53-mediated apoptosis and fibrosis pathways along with markers for oxidative stress and inflammation in mice myocardium. 7 week old, male, C57Bl/6 mice were exposed to 6Gy (H) or 5cGy followed 24hr later with 6Gy (LH) 137Cs gamma radiation. Mice were sacrificed and their hearts extirpated 4, 24, or 72hr after final irradiation. Real Time - Polymerase Chain Reaction was used to evaluate target genes. Apoptotic genes Bad and Bax, pro-cell survival genes Bcl2 and Bcl2l2, fibrosis gene Vegfa, and oxidative stress genes Sod2 and GPx4 showed a reduced fold regulation change (Bad,-6.18; Bax,-6.94; Bcl2,-5.09; Bcl2l2,-4.03; Vegfa, -11.84; Sod2,-5.97; GPx4*,-28.72; * = Bonferroni adjusted p-value < or = 0.003) 4hr after H, but not after 4hr LH compared to control. Other p53-mediated apoptosis genes Casp3, Casp9, Trp53, and Myc exhibited down-regulation but did not achieve a notable level of significance 4hr after H. 24hr after H, genetic down-regulation was no longer present compared to 24hr control. These data suggest a general reduction in genetic expression 4hrs after a high dose of gamma radiation. However, pre-exposure to 5cGy gamma radiation appears to facilitate a radio-adaptive response that mitigates the reduction in genetic expression associated with single high-dose gamma radiation exposure. This radio-adaptive response may serve as a potential countermeasure to radiation-induced myocardial remodeling and preserve the cardiovascular health of astronauts; thus, reducing the risks of human space exploration.

Westby, Christian M.↗
NASA NTRS2011

Fire Return Interval Within the Northern Boundary of the Larch Forest

Larch (Larix spp.) dominant forests compose a large proportion of the forests of Russia (i.e., about 40% of forested areas). These forests range from the Yenisei ridge on the west to the Pacific Ocean on the east, and from Lake Baikal on the south to the 73rd parallel in the north. Larch stands comprise the world s northern most forest at Ary-Mas (72 deg 28' N, 102 deg 15' E). Larch dominated forests occupy about 70% of the permafrost areas in Siberia. Larch forms high closure stands as well as open forests, and is found mainly over permafrost, where other tree species barely survive. Wildfires are typical for this territory with the majority occurring as ground fires due to low crown closure. Due to the thin active layer in permafrost soils and a dense lichen-moss cover, ground fires may cause stand mortality. The vast areas of larch-dominant forests is generally considered as a "carbon sink"; however, positive long-term temperature trends at higher latitudes are expected to result in an increase of fire frequency, and thus may convert this area to a source for greenhouse gases. There are recent observations regarding the increase of fire frequency within non-protected territories. Surprisingly, there are few publications on fire chronoseqences for the huge forested territory between the Ural Mountains and the Pacific Ocean. Also there is a general understanding that bimodal (late spring -- early summer and late summer-beginning of fall) fire seasonal distribution in the south becomes uni-modal (late spring -- early summer) in the north. The purpose of this study is to investigate the wildfire history at the northern edge of the zone of larch dominance.

Kharuk, V. I.↗
NASA NTRS2011

NEEMO 15: Evaluation of Human Exploration Systems for Near-Earth Asteroids

The NASA Extreme Environment Mission Operations (NEEMO) 15 mission was focused on near-Earth Asteroid (NEA) exploration techniques evaluation. It began with a University of Delaware autonomous underwater vehicle (AUV) systematically mapping the coral reef for hundreds of meters surrounding the Aquarius habitat. This activity is akin to the type of "far field survey" approach that may be used by a robotic precursor in advance of a human mission to a NEA. Data from the far-field survey were then examined by the NEEMO science team and follow-up exploration traverses were planned, which used Deepworker single-person submersibles. Science traverses at NEEMO 15 were planned according to a prioritized list of scientific objectives developed by the science team based on review and discussion of previous related marine science research including previous marine science saturation missions conducted at the Aquarius habitat. AUV data was used to select several areas of scientific interest. The Deepworker science traverses were then executed at these areas of interest during 4 days of the NEEMO 15 mission and provided higher resolution data such as coral species distribution and mortality. These traverses are analogous to the "near field survey" approach that is expected to be performed by a multi mission space exploration vehicle (MMSEV) during a human mission to a NEA before conducting extravehicular activities (EVA)s. In addition to the science objectives that were pursued, the NEEMO 15 science traverses provided an opportunity to test newly developed software and techniques. Sample collection and instrument deployment on the NEA surface by EVA crew would follow the "near field survey" in a human NEA mission. Sample collection was not necessary for the purposes of the NEEMO science objectives; however, the engineering and operations objectives during NEEMO 15 were to evaluate different combinations of vehicles, crewmembers, tools, and equipment that could be used to perform these tasks on a NEA. Specifically, the productivity and acceptability of simulated NEA exploration activities were systematically quantified and compared when operating with different combinations of crew sizes and exploration systems including MMSEVs, EVA jet packs, and EVA translation devices.

Chappell, Steven P.↗
NASA NTRS2011

The First Intervention Study in Elder Self-Neglect: A Randomized Clinical Trial to Improve Vitamin D Levels

Despite high mortality rates, elder self-neglect is characterized by refusal of medical and social interventions. To date there have been no tested clinical interventions in elders who self-neglect. Previous research from the TEAM Institute has shown significantly low vitamin D levels in this population. This study aimed to determine the feasibility of a clinical intervention. Replacement of vitamin D was chosen because of its ease of administration and favorable safety profile. Methods: A randomized clinical trial using directly observed therapy of vitamin D was conducted using 50 elders, >65 years of age, with Adult Protective Services (APS) validated self-neglect. A staggered intervention with waiting controls was used to maximize statistical power. One-third (n=17) of the group was administered 50,000 IU vitamin D2 (ergocalciferol) monthly and the remainder (n=33) were administered 400 IU monthly. Serum 25-OH vitamin D was assessed at baseline and 5-months. Results: 69% agreed to participate in the study and of those n=40 (80%) remained at 5-months. At baseline, 12% (n=7) were deficient in vitamin D (<30nmol/L) and approximately 38% (n=22) had inadequate vitamin D levels (<50nmol/L). The baseline 25-OH vitamin D level was 59 nmol/L +25 (mean SD), and increased significantly to 72nmol/L +21 nmol/L at 5-months. Conclusion: These data are the first to provide evidence that clinical interventions are feasible in elders who self-neglect. The increase in vitamin D levels confirmed that the study personnel were able to successfully intervene community-dwelling elders with self-neglect. This study sets the precedent for future intervention and prevention studies

Burnett, Jason↗
NASA NTRS2012

Technical Evaluation of the NASA Model for Cancer Risk to Astronauts Due to Space Radiation

At the request of NASA, the National Research Council's (NRC's) Committee for Evaluation of Space Radiation Cancer Risk Model1 reviewed a number of changes that NASA proposes to make to its model for estimating the risk of radiation-induced cancer in astronauts. The NASA model in current use was last updated in 2005, and the proposed model would incorporate recent research directed at improving the quantification and understanding of the health risks posed by the space radiation environment. NASA's proposed model is defined by the 2011 NASA report Space Radiation Cancer Risk Projections and Uncertainties--2010 . The committee's evaluation is based primarily on this source, which is referred to hereafter as the 2011 NASA report, with mention of specific sections or tables. The overall process for estimating cancer risks due to low linear energy transfer (LET) radiation exposure has been fully described in reports by a number of organizations. The approaches described in the reports from all of these expert groups are quite similar. NASA's proposed space radiation cancer risk assessment model calculates, as its main output, age- and gender-specific risk of exposure-induced death (REID) for use in the estimation of mission and astronaut-specific cancer risk. The model also calculates the associated uncertainties in REID. The general approach for estimating risk and uncertainty in the proposed model is broadly similar to that used for the current (2005) NASA model and is based on recommendations by the National Council on Radiation Protection and Measurements. However, NASA's proposed model has significant changes with respect to the following: the integration of new findings and methods into its components by taking into account newer epidemiological data and analyses, new radiobiological data indicating that quality factors differ for leukemia and solid cancers, an improved method for specifying quality factors in terms of radiation track structure concepts as opposed to the previous approach based on linear energy transfer, the development of a new solar particle event (SPE) model, and the updates to galactic cosmic ray (GCR) and shielding transport models. The newer epidemiological information includes updates to the cancer incidence rates from the life span study (LSS) of the Japanese atomic bomb survivors, transferred to the U.S. population and converted to cancer mortality rates from U.S. population statistics. In addition, the proposed model provides an alternative analysis applicable to lifetime never-smokers (NSs). Details of the uncertainty analysis in the model have also been updated and revised. NASA's proposed model and associated uncertainties are complex in their formulation and as such require a very clear and precise set of descriptions. The committee found the 2011 NASA report challenging to review largely because of the lack of clarity in the model descriptions and derivation of the various parameters used. The committee requested some clarifications from NASA throughout its review and was able to resolve many, but not all, of the ambiguities in the written description.

Source record↗
NASA NTRS2011

Cryogenic Quenching Process for Electronic Part Screening

The use of electronic parts at cryogenic temperatures (less than 100 C) for extreme environments is not well controlled or developed from a product quality and reliability point of view. This is in contrast to the very rigorous and well-documented procedures to qualify electronic parts for mission use in the 55 to 125 C temperature range. A similarly rigorous methodology for screening and evaluating electronic parts needs to be developed so that mission planners can expect the same level of high reliability performance for parts operated at cryogenic temperatures. A formal methodology for screening and qualifying electronic parts at cryogenic temperatures has been proposed. The methodology focuses on the base physics of failure of the devices at cryogenic temperatures. All electronic part reliability is based on the bathtub curve, high amounts of initial failures (infant mortals), a long period of normal use (random failures), and then an increasing number of failures (end of life). Unique to this is the development of custom screening procedures to eliminate early failures at cold temperatures. The ability to screen out defects will specifically impact reliability at cold temperatures. Cryogenic reliability is limited by electron trap creation in the oxide and defect sites at conductor interfaces. Non-uniform conduction processes due to process marginalities will be magnified at cryogenic temperatures. Carrier mobilities change by orders of magnitude at cryogenic temperatures, significantly enhancing the effects of electric field. Marginal contacts, impurities in oxides, and defects in conductor/conductor interfaces can all be magnified at low temperatures. The novelty is the use of an ultra-low temperature, short-duration quenching process for defect screening. The quenching process is designed to identify those defects that will precisely (and negatively) affect long-term, cryogenic part operation. This quenching process occurs at a temperature that is at least 25 C colder than the coldest expected operating temperature. This quenching process is the opposite of the standard burn-in procedure. Normal burn-in raises the temperature (and voltage) to activate quickly any possible manufacturing defects remaining in the device that were not already rejected at a functional test step. The proposed inverse burn-in or quenching process is custom-tailored to the electronic device being used. The doping profiles, materials, minimum dimensions, interfaces, and thermal expansion coefficients are all taken into account in determining the ramp rate, dwell time, and temperature.

Sheldon, Douglas J.↗
NASA NTRS2012

Technical Evaluation of the NASA Model for Cancer Risk to Astronauts Due to Space Radiation

At the request of NASA, the National Research Council's (NRC's) Committee for Evaluation of Space Radiation Cancer Risk Model reviewed a number of changes that NASA proposes to make to its model for estimating the risk of radiation-induced cancer in astronauts. The NASA model in current use was last updated in 2005, and the proposed model would incorporate recent research directed at improving the quantification and understanding of the health risks posed by the space radiation environment. NASA's proposed model is defined by the 2011 NASA report Space Radiation Cancer Risk Projections and Uncertainties 2010 (Cucinotta et al., 2011). The committee's evaluation is based primarily on this source, which is referred to hereafter as the 2011 NASA report, with mention of specific sections or tables cited more formally as Cucinotta et al. (2011). The overall process for estimating cancer risks due to low linear energy transfer (LET) radiation exposure has been fully described in reports by a number of organizations. They include, more recently: (1) The "BEIR VII Phase 2" report from the NRC's Committee on Biological Effects of Ionizing Radiation (BEIR) (NRC, 2006); (2) Studies of Radiation and Cancer from the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR, 2006), (3) The 2007 Recommendations of the International Commission on Radiological Protection (ICRP), ICRP Publication 103 (ICRP, 2007); and (4) The Environmental Protection Agency s (EPA s) report EPA Radiogenic Cancer Risk Models and Projections for the U.S. Population (EPA, 2011). The approaches described in the reports from all of these expert groups are quite similar. NASA's proposed space radiation cancer risk assessment model calculates, as its main output, age- and gender-specific risk of exposure-induced death (REID) for use in the estimation of mission and astronaut-specific cancer risk. The model also calculates the associated uncertainties in REID. The general approach for estimating risk and uncertainty in the proposed model is broadly similar to that used for the current (2005) NASA model and is based on recommendations by the National Council on Radiation Protection and Measurements (NCRP, 2000, 2006). However, NASA's proposed model has significant changes with respect to the following: the integration of new findings and methods into its components by taking into account newer epidemiological data and analyses, new radiobiological data indicating that quality factors differ for leukemia and solid cancers, an improved method for specifying quality factors in terms of radiation track structure concepts as opposed to the previous approach based on linear energy transfer, the development of a new solar particle event (SPE) model, and the updates to galactic cosmic ray (GCR) and shielding transport models. The newer epidemiological information includes updates to the cancer incidence rates from the life span study (LSS) of the Japanese atomic bomb survivors (Preston et al., 2007), transferred to the U.S. population and converted to cancer mortality rates from U.S. population statistics. In addition, the proposed model provides an alternative analysis applicable to lifetime never-smokers (NSs). Details of the uncertainty analysis in the model have also been updated and revised. NASA's proposed model and associated uncertainties are complex in their formulation and as such require a very clear and precise set of descriptions. The committee found the 2011 NASA report challenging to review largely because of the lack of clarity in the model descriptions and derivation of the various parameters used. The committee requested some clarifications from NASA throughout its review and was able to resolve many, but not all, of the ambiguities in the written description.

Source record↗
NASA NTRS2012

Use of Statistical Analysis of Acoustic Emission Data on Carbon-Epoxy COPV Materials-of-Construction for Enhanced Felicity Ratio Onset Determination

Broadband modal acoustic emission (AE) data were acquired during intermittent load hold tensile test profiles on Toray T1000G carbon fiber-reinforced epoxy (C/Ep) single tow specimens. A novel trend seeking statistical method to determine the onset of significant AE was developed, resulting in more linear decreases in the Felicity ratio (FR) with load, potentially leading to more accurate failure prediction. The method developed uses an exponentially weighted moving average (EWMA) control chart. Comparison of the EWMA with previously used FR onset methods, namely the discrete (n), mean (n (raised bar)), normalized (n%) and normalized mean (n(raised bar)%) methods, revealed the EWMA method yields more consistently linear FR versus load relationships between specimens. Other findings include a correlation between AE data richness and FR linearity based on the FR methods discussed in this paper, and evidence of premature failure at lower than expected loads. Application of the EWMA method should be extended to other composite materials and, eventually, composite components such as composite overwrapped pressure vessels. Furthermore, future experiments should attempt to uncover the factors responsible for infant mortality in C/Ep strands.

Abraham, Arick Reed A.↗
NASA NTRS2012

Some Aspects of the Failure Mechanisms in BaTiO3-Based Multilayer Ceramic Capacitors

The objective of this presentation is to gain insight into possible failure mechanisms in BaTiO3-based ceramic capacitors that may be associated with the reliability degradation that accompanies a reduction in dielectric thickness, as reported by Intel Corporation in 2010. The volumetric efficiency (microF/cm3) of a multilayer ceramic capacitor (MLCC) has been shown to not increase limitlessly due to the grain size effect on the dielectric constant of ferroelectric ceramic BaTiO3 material. The reliability of an MLCC has been discussed with respect to its structure. The MLCCs with higher numbers of dielectric layers will pose more challenges for the reliability of dielectric material, which is the case for most base-metal-electrode (BME) capacitors. A number of MLCCs manufactured using both precious-metal-electrode (PME) and BME technology, with 25 V rating and various chip sizes and capacitances, were tested at accelerated stress levels. Most of these MLCCs had a failure behavior with two mixed failure modes: the well-known rapid dielectric wearout, and so-called 'early failures." The two failure modes can be distinguished when the testing data were presented and normalized at use-level using a 2-parameter Weibull plot. The early failures had a slope parameter of Beta >1, indicating that the early failures are not infant mortalities. Early failures are triggered due to external electrical overstress and become dominant as dielectric layer thickness decreases, accompanied by a dramatic reduction in reliability. This indicates that early failures are the main cause of the reliability degradation in MLCCs as dielectric layer thickness decreases. All of the early failures are characterized by an avalanche-like breakdown leakage current. The failures have been attributed to the extrinsic minor construction defects introduced during fabrication of the capacitors. A reliability model including dielectric thickness and extrinsic defect feature size is proposed in this presentation. The model can be used to explain the Intel-reported reliability degradation in MLCCs with respect to the reduction of dielectric thickness. It can also be used to estimate the reliability of a MLCC based on its construction and microstructure parameters such as dielectric thickness, average grain size, and number of dielectric layers. Measures for preventing early failures are also discussed in this document.

Liu, David Donhang↗
NASA NTRS2012

Paramyxovirus Infection Mimics In Vivo Cellular Dynamics in Three-Demensional Human Bronchio-Epithelial Tissue-Like Assemblies

Respiratory syncytial virus and parainfluenza virus cause severe respiratory disease, especially in infants, children and the elderly. An in vitro model that accurately mimics infection of the human respiratory epithelium (HRE) would facilitate vaccine development greatly. Monolayer cultures traditionally used to study these viruses do not accurately and precisely differentiate the replication efficiencies of wild type and attenuated viruses. Therefore, we engineered novel three-dimensional (3D) tissue-like assemblies (TLAs) of human broncho-epithelial (HBE) cells to produce a more physiologically relevant in vitro model of the HRE. TLAs resemble HRE structurally and by expression of differentiated epithelial cell markers. Most significantly, wild type viruses exhibited a clear growth advantage over attenuated strains in TLAs unlike monolayer cultures. In addition, the TLAs responded to virus infection by secreting pro-inflammatory mediators similar to the respiratory epithelia of infected children. These characteristics make the TLA model a valuable platform technology to develop and evaluate live, attenuated respiratory virus vaccine candidates for human use. Respiratory virus diseases, the most frequent and least preventable of all infectious diseases, range in severity from the common cold to severe bronchiolitis and pneumonia . Two paramyxoviruses, respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3), are responsible for a majority of the most severe respiratory diseases of infants and young children. RSV causes 70% of all bronchiolitis cases and is a major cause of morbidity and mortality worldwide, especially in infants. PIV3 causes 10-15% of bronchiolitis and pneumonia during infancy, second only to RSV, and 40% of croup in infants To date, licensed vaccines are not available to prevent these respiratory diseases. At present, traditional monkey kidney (Vero and LLC-MK2) and human (HEp-2) tissue culture cells and small animal models (mouse, cotton rat, guinea pig, ferret, and hamster) fail to accurately imitate viral replication and human disease states (8). Lacking an authentic model has impeded the development and evaluation of live, attenuated vaccine candidates. Development of a physiologically relevant in vitro tissue culture model that reproduces characteristics of the HRE, the primary target of RSV and PIV3, would aid in predicting clinical attenuation and safety of vaccine candidates. Successful tissue engineering of a 3D human intestinal model using novel NASA technology inspired the development of a tri-culture 3D model for the HRE. Sequential layering of primary mesenchymal cells (comprised of normal human fibroblasts and endothelial cells) followed by BEAS-2B epithelial cells derived from human bronchi and tracheae were recapitulated on Cultisphere and/or cytodex3 microcarriers in cylindrical vessels that rotate horizontally creating an organized epithelial structure. Horizontal rotation randomizes the gravity vector modeling aspects of microgravity. Mesenchymal and epithelial cells grown under these conditions reproduce the structural organization, multi-cellular complexity, and differentiation state of the HRE. The opportunity to study respiratory viruses in a nasal epithelium model is invaluable because the most promising respiratory virus vaccine candidates are live attenuated viruses for intranasal administration. Here we characterize the interactions of respiratory viruses and epithelial cells grown under modeled microgravity in comparison to gravity-ladened monolayers. 3D HBE TLAs and traditional monolayers (2D) are infected at 35 C, the upper temperature of the upper HRE, to simulate in vivo infection conditions. Growth kinetics of wild type (wt) RSV and PIV3 viruses were compared in 2D and 3D cells to that of strains attenuated in humans or rhesus macaques. This novel 3D HBE model also offers an opportunity to study whether the epithelial cell function, especially in host defenses recapitulated by mimicking the structural organization of the HRE. In vivo, airway epithelial cells play a significant and dynamic role in host defense by blocking paracellular permeability and modulating airway function through cellular interactions or tight junctions. As regulators of the innate immune response, epithelial cells constitutively express cytokines, chemokines, and colony stimulating factors including RANTES, IL-8, IL-6, GM-CSF, and G-CSF for proactive host defense. In response to viral infection, epithelial cells induce potent immuno-modulatory and pro-inflammatory cytokines that recruit phagocytic and inflammatory cells to clear the virus and enhance protection. Although disease pathogenesis is classically attributed to the cytopathic effects of the pathogen, severe disease states associated with RSV and PIV3 are attributed to the inflammatory response, especially in infants. RSV is a potent inducer of cytokines and pro-inflammatory mediators in epithelial cells in vivo. A differentiated human epithelial model independent of the complete functional immune system will help elucidate the role of epithelial cells in respiratory disease. We reported here, virus and host cell interactions in 3D HBE TLAs are similar to that in vivo. Because the epithelial cell organization of the TLAs impacts not only the expression of airway epithelial characteristics, but also cellular communication, the TLAs represent a more physiologically relevant model of the HRE than BEAS-2B or other non-tumour monolayer models of respiratory disease. As a result, wild type respiratory viruses have a clear growth advantage over attenuated viruses in TLAs unlike traditional monolayers. In addition, the TLAs respond to wild type virus infection by secreting pro-inflammatory mediators characteristic of infected HRE. TLAs expressing microbial defense mechanisms provide an excellent model to study the interactions of respiratory pathogens with their host and to identify the innate immunity mediators. Therefore, 3D HBE TLAs offer advantages for the study of respiratory viruses and the development of viral vaccine candidates.

Deatly, Anne M.↗
NASA NTRS2010

Modelling the Future Hydroclimatology of the Lower Fraser River and its Impacts on the Spawning Migration Survival of Sockeye Salmon

Short episodic high temperature events can be lethal for migrating adult Pacific salmon (Oncorhynchus spp.). We downscaled temperatures for the Fraser River, British Columbia to evaluate the impact of climate warming on the frequency of exceeding thermal thresholds associated with salmon migratory success. Alarmingly, a modest 1.0 C increase in average summer water temperature over 100 years (1981-2000 to 2081-2100) tripled the number of days per year exceeding critical salmonid thermal thresholds (i.e. 19.0 C). Refined thresholds for two populations (Gates Creek and Weaver Creek) of sockeye salmon (Oncorhynchus nerka) were defined using physiological constraint models based on aerobic scope. While extreme temperatures leading to complete aerobic collapse remained unlikely under our warming scenario, both populations were increasingly forced to migrate upriver at reduced levels of aerobic performance (e.g. in 80% of future simulations, => 90% of salmon encountered temperatures exceeding population specific thermal optima for maximum aerobic scope; T(sub opt)) = 16.3 C for Gates Creek and T(sub sopt)=14.5 C for Weaver Creek). Assuming recent changes to river entry timing persist, we also predicted dramatic increases in the probability of freshwater mortality for Weaver Creek salmon due to reductions in aerobic, and general physiological, performance (e.g. in 42% of future simulations =>50% of Weaver Creek fish exceeded temperature thresholds associated with 0 - 60% of maximum aerobic scope). Potential for adaptation via directional selection on run-timing was more evident for the Weaver Creek population. Early entry Weaver Creek fish experienced 25% (range: 15 - 31%) more suboptimal temperatures than late entrants, compared with an 8% difference (range: 0 - 17%) between early and late Gates Creek fish. Our results emphasize the need to consider daily temperature variability in association with population-specific differences in behaviour and physiological constraints when forecasting impacts of climate change on migratory survival of aquatic species.

Hague, M. J.↗
NASA NTRS2012

Using NASA Environmental Data to Enhance Public Health Decision Making

The Universities Space Research Association at the NASA Marshall Space Flight Center is collaborating with the University of Alabama at Birmingham (UAB) School of Public Health and the Centers for Disease Control and Prevention (CDC) to address issues of environmental health and enhance public health decision making by utilizing NASA remotely sensed data and products. The objectives of this collaboration are to develop high-quality spatial data sets of environmental variables, and deliver the data sets and associated analyses to local, state and federal end-user groups. These data can be linked spatially and temporally to public health data, such as mortality and disease morbidity, for further analysis and decision making. Three daily environmental data sets have been developed for the conterminous U.S. on different spatial resolutions for the time period 2003-2008: (1) spatial surfaces of estimated fine particulate matter (PM2.5) exposures on a 10-km grid utilizing the US Environmental Protection Agency (EPA) ground observations and NASA s MODerate-resolution Imaging Spectroradiometer (MODIS) data; (2) a 1-km grid of Land Surface Temperature (LST) using MODIS data; and (3) a 12-km grid of daily Solar Insolation (SI) and maximum and minimum air temperature using the North American Land Data Assimilation System (NLDAS) forcing data. These environmental data sets will be linked with public health data from the UAB REasons for Geographic And Racial Differences in Stroke (REGARDS) national cohort study to determine whether exposures to these environmental risk factors are related to cognitive decline and other health outcomes. These environmental datasets and public health linkage analyses will be made available to public health professionals, researchers and the general public through the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) system and through peer reviewed publications. To date, two of the data sets have been released to the public in CDC WONDER, Daily Air Temperature and Heat Index for years 1979-2010, and Daily Fine Particulate Matter (PM2.5) air quality measures for years 2003-2008. These data in CDC WONDER can be aggregated to the county-level, state-level, or regional-level as per users need and downloaded in tabular, graphical, and map formats. The summary statistical output are available to web and app developers via the WONDER Application Programming Interface (API). The linkage of these data with the CDC WONDER system provides a significant addition to CDC WONDER, allowing public health researchers and policy makers to better include environmental exposure data in the context of other health data available in CDC WONDER online system. It also substantially expands public access to NASA environmental data, making their use by a wide range of decision makers feasible.

Al-Hamdan, Mohammad↗
NASA NTRS2012

Space Radiation Cancer Risks and Uncertainities for Different Mission Time Periods

Space radiation consists of solar particle events (SPEs), comprised largely of medium energy protons (less than several hundred MeV); and galactic cosmic ray (GCR), which includes high energy protons and high charge and energy (HZE) nuclei. For long duration missions, space radiation presents significant health risks including cancer mortality. Probabilistic risk assessment (PRA) is essential for radiation protection of crews on long term space missions outside of the protection of the Earth s magnetic field and for optimization of mission planning and costs. For the assessment of organ dosimetric quantities and cancer risks, the particle spectra at each critical body organs must be characterized. In implementing a PRA approach, a statistical model of SPE fluence was developed, because the individual SPE occurrences themselves are random in nature while the frequency distribution of SPEs depends strongly upon the phase within the solar activity cycle. Spectral variability of SPEs was also examined, because the detailed energy spectra of protons are important especially at high energy levels for assessing the cancer risk associated with energetic particles for large events. An overall cumulative probability of a GCR environment for a specified mission period was estimated for the temporal characterization of the GCR environment represented by the deceleration potential (theta). Finally, this probabilistic approach to space radiation cancer risk was coupled with a model of the radiobiological factors and uncertainties in projecting cancer risks. Probabilities of fatal cancer risk and 95% confidence intervals will be reported for various periods of space missions.

Kim,Myung-Hee Y.↗
NASA NTRS2013

The Lifetime Surveillance of Astronaut Health (LSAH) Project

From 1989-2010 NASA conducted a research study, the Longitudinal Study of Astronaut Health, to investigate the incidence of acute and chronic morbidity and mortality in astronauts and to determine whether their occupational exposures were associated with increased risk of death or disability. In 2004, the Institute of Medicine recommended that NASA convert the longitudinal study into an occupational health surveillance program and in 2010, NASA initiated the Lifetime Surveillance of Astronaut Health project. The new program collects data on astronaut workplace exposures, especially those occurring in the training and space flight environments, and conducts operational and health care analyses to look for trends in exposure and health outcomes. Astronaut selection and retention medical standards are rigorous, requiring an extensive clinical testing regimen. As a result, this employee population has contributed to a large set of health data available for analyses. Astronauts represent a special population with occupational exposures not typically experienced by other employee populations. Additionally, astronauts are different from the general population in terms of demographic and physiologic characteristics. The challenges and benefits of conducting health surveillance for an employee population with unique occupational exposures will be discussed. Several occupational surveillance projects currently underway to examine associations between astronaut workplace exposures and medical outcomes will be described.

Bopp, Eugenia↗
NASA NTRS2012

Dirtier Air from a Weaker Monsoon

The level of air pollution in China has much increased in the past decades, causing serious health problems. Among the main pollutants are aerosols, also known as particulate matter: tiny, invisible particles that are suspended in the air. These particles contribute substantially to premature mortality associated with cardiopulmonary diseases and lung cancer1. The increase of the aerosol level in China has been commonly attributed to the fast rise in pollutant emissions from the rapid economic development in the region. However, writing in Geophysical Research Letters, Jianlei Zhu and colleagues2 tell a different side of the story: using a chemical transport model and observation data, they show that the decadal scale weakening of the East Asian summer monsoon has also contributed to the increase of aerosol concentrations in China. The life cycle of atmospheric aerosols starts with its emission or formation in the atmosphere. Some aerosol components such as dust, soot and sea salt are emitted directly as particles to the atmosphere, but others are formed there by way of photochemical reactions. For example, sulphate and nitrate aerosols are produced from their respective precursor gases, sulphur dioxide and nitrogen oxides. Aerosol particles can be transported away from their source locations by winds or vertical motion of the air. Eventually, they are removed from the atmosphere by means of dry deposition and wet scavenging by precipitation. Measurements generally show that aerosol concentrations over Asia are lowest during the summer monsoon season3, because intense rainfall efficiently removes them from the air. The East Asian summer monsoon extends over subtropics and mid-latitudes. Its rainfall tends to concentrate in rain belts that stretch out for many thousands of kilometres and affect China, Korea, Japan and the surrounding area. Observations suggest that the East Asian summer monsoon circulation and precipitation have been in decline since the 1970s4. In particular, a weaker East Asian summer monsoon is characterized by weaker southerly or southwesterly winds, a deficit in rainfall over northern China and larger rainfalls in southern China. By contrast, when the East Asian summer monsoon is strong, the southerly winds and strong rainfalls extend to northern China. The decadal scale decline in the strength of the East Asian summer monsoon since the 1970s would imply an increase in aerosol concentrations in northern China, north of 28deg N, and a decrease in southern China if emissions were kept the same. One obvious reason for this direction of aerosol change is that the reduction of monsoon rainfall in northern China would cause less wet scavenging of aerosols by precipitation. Zhu et al.2 investigated this relationship between aerosol concentrations and the strength of the East Asian summer monsoon and showed that the two parameters have strong negative correlations: the summer aerosol concentrations near the surface over eastern China.

Chin, Mian↗
NASA NTRS2014

Modeling of Blood Lead Levels in Astronauts Exposed to Lead from Microgravity-Accelerated Bone Loss

Human exposure to lead has been associated with toxicity to multiple organ systems. Studies of various population groups with relatively low blood lead concentrations (<10 μg/dL) have indicated associations of blood lead level with lower cognitive test scores in children, later onset of puberty in girls, and increased blood pressure and cardiovascular mortality rates in adults. Cognitive effects are considered by regulatory agencies to be the most sensitive endpoint at low doses. Although ~95% of the body burden of lead is stored in the bones, the adverse effects of lead correlate with the concentration of lead in the blood better than with that in the bones. NASA has found that prolonged exposure to microgravity during spaceflight results in a significant loss of bone minerals, the extent of which varies from individual to individual and from bone to bone, but generally averages about 0.5% per month. During such bone loss, lead that had been stored in bones would be released along with calcium. The effects on the concentration of lead in the blood (PbB) of various concentrations of lead in drinking water (PbW) and of lead released from bones due to accelerated osteoporosis in microgravity, as well as changes in exposure to environmental lead before, during, and after spaceflight were evaluated using a physiologically based pharmacokinetic (PBPK) model that incorporated exposure to environmental lead both on earth and in flight and included temporarily increased rates of osteoporosis during spaceflight.

Garcia, H.↗