Search NASA⌕ Search

SEARCH · Search NASA

Results for “DISEASES”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 901 records · Page 50
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Deletion of the EP296R Gene from the Genome of Highly Virulent African Swine Fever Virus Georgia 2010 Does Not Affect Virus Replication or Virulence in Domestic Pigs

African swine fever virus (ASFV) causes a lethal disease (ASF) in domestic pigs, African swine fever (ASF). ASF is currently producing a pandemic affecting pig production across Eurasia, leading to a shortage of food accessibility. ASFV is structurally complex, harboring a large genome encoding over 150 genes. One of them, EP296R, has been shown to encode for an endonuclease that is necessary for the efficient replication of the virus in swine macrophages, the natural ASFV target cell. Here, we report the development of a recombinant virus, ASFV-G-ΔEP296R, harboring the deletion of the EP296R gene from the genome of the highly virulent field isolate ASFV Georgia 2010 (ASFV-G). The recombinant ASFV-G-ΔEP296R replicates in primary swine macrophages with similar kinetics as the parental virus ASFV-G. Pigs experimentally infected by the intramuscular route with 102 HAD50 show a slightly protracted, although lethal, presentation of the disease when compared to that of animals inoculated with parental ASFV-G. Viremia titers in the ASFV-G-ΔEP296R-infected animals closely followed the kinetics of presentation of clinical disease. Results presented here demonstrate that ASFV-G-ΔEP296R is not essential for the processes of ASFV replication in swine macrophages, nor is it radically involved in the process of virus replication or disease production in domestic pigs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Targeted alpha therapy in a systemic mouse model of prostate cancer - a feasibility study

225 Ac-PSMA-617 targeted-therapy has demonstrated efficacy in 75-85% of patients; however, responses are not durable. We aimed to establish translatable mouse models of disseminated prostate cancer (PCa) to evaluate effectiveness of 225 Ac-PSMA-617 at various disease stages. Methods: C4-2, C4-2B, or 22Rv1 cells were injected into the left ventricle of male NSG mice. Disease progression was monitored using bioluminescence imaging (BLI). For treatment, mice were injected with 40 kBq 225 Ac-PSMA-617 at one (early treatment cohort) or three weeks (late treatment cohort) post-inoculation. Treatment efficacy was monitored by BLI of whole-body tumor burden. Mice were sacrificed based on body conditioning score. Results: C4-2 cells yielded metastases in liver, lungs, spleen, stomach, bones, and brain - achieving a clinically relevant model of widespread metastatic disease. The disease burden in the early treatment cohort was stable over 27 weeks in 5/9 mice and progressive in 4/9 mice. These mice were sacrificed due to brain metastases. Median survival of the late treatment cohort was superior to controls (13 vs. 7 weeks; p<0.0001) but inferior to that in the early treatment cohort (13 vs. 27 weeks; p<0.001). Late cohort mice succumbed to extensive liver involvement. The 22Rv1 and C4-2B systemic models were not used for treatment due to high kidney metastatic burden or low take rate, respectively. Conclusion: C4-2 cells reproduced metastatic cancer spread most relevantly. Early treatment with 225 Ac-PSMA-617 prevented liver metastases and led to significant survival benefit. Late treatment improved survival without reducing tumor burden in the liver, the main site of metastasis. The current findings suggest that early 225 Ac-PSMA-617 intervention is more efficacious in the setting of widespread metastatic PCa.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗
NASA NTRS1975

Evaluation of early recognition of viral infections in man

The potential of Lymphocyte Specific Gravity Distribution (LSGD) as a non-specific procedure for early diagnosis of viral disease in astronauts is considered. Results of experiments and a literature search show that several virus diseases result in distinctive changes in the specific gravity distribution of peripheral blood lymphocytes as a result of disease process and associated immune response. A tentative model is proposed which relates the shape of LSGD to the identity of subpopulations of peripheral lymphocytes in a preclinical viral disease situation.

Kelton, A. A.↗
NASA NTRS1987

A solid phase enzyme-linked immunosorbent assay for the antigenic detection of Legionella pneumophila (serogroup 1): A compliment for the space station diagnostic capability

It is necessary that an adequate microbiology capability be provided as part of the Health Maintenance Facility (HMF) to support expected microbial disease events and environmental monitoring during long periods of space flight. The application of morphological and biochemical studies to confirm the presence of certain bacterial and fungal disease agents are currently available and under consideration. This confirmation would be facilitated through employment of serological methods to aid in the identification of bacterial, fungal, and viral agents. A number of serological approaches are currently being considered, including the use of Enzyme Linked Immunosorbent Assay (ELISA) technology, which could be utilized during microgravity conditions. A solid phase, membrane supported ELISA for the detection of Legionella pneumophila, an expected disease agent, was developed to show a potential model system that would meet the HMF requirements and specifications for the future space station. These studies demonstrate the capability of membrane supported ELISA systems for identification of expected microbial disease agents as part of the HMF.

Hejtmancik, Kelly E.↗
NASA NTRS2002

Satellites as Shared Resources for Caribbean Climate and Health Studies

Remotely-sensed data and observations are providing powerful new tools for addressing climate and environment-related human health problems through increased capabilities for monitoring, risk mapping, and surveillance of parameters useful to such problems as vector-borne and infectious diseases, air and water quality, harmful algal blooms, UV (ultraviolet) radiation, contaminant and pathogen transport in air and water, and thermal stress. Remote sensing, geographic information systems (GIS), global positioning systems (GPS), improved computational capabilities, and interdisciplinary research between the Earth and health science communities are being combined in rich collaborative efforts resulting in more rapid problem-solving, early warning, and prevention in global health issues. Collaborative efforts among scientists from health and Earth sciences together with local decision-makers are enabling increased understanding of the relationships between changes in temperature, rainfall, wind, soil moisture, solar radiation, vegetation, and the patterns of extreme weather events and the occurrence and patterns of diseases (especially, infectious and vector-borne diseases) and other health problems. This increased understanding through improved information and data sharing, in turn, empowers local health and environmental officials to better predict health problems, take preventive measure, and improve response actions. This paper summarizes the remote sensing systems most useful for climate, environment and health studies of the Caribbean region and provides several examples of interdisciplinary research projects in the Caribbean currently using remote sensing technologies. These summaries include the use of remote sensing of algal blooms, pollution transport, coral reef monitoring, vectorborne disease studies, and potential health effects of African dust on Trinidad and Barbados.

Maynard, Nancy G.↗
NASA NTRS2001

Biomarkers of exposure and dose: state of the art

Biomarkers provide methods to measure changes in biological systems and to relate them to environmental insults and disease processes. Biomarkers can be classified as markers of exposure and dose, markers of sensitivity, and markers of disease. It is important that the differences and applications of the various types of biomarkers be clearly understood. The military is primarily interested in early biomarkers of exposure and dose that do not require high levels of sensitivity but can be used to rapidly triage war fighters under combat or terrorist conditions and determine which, if any, require medical attention. Biomarkers of long-term radiation risk represent the second area of interest for the military. Biomarkers of risk require high sensitivity and specificity for the disease and insult but do not require rapid data turnaround. Biomarkers will help provide information for quick command decisions in the field, characterise long-term troop risks and identify early stages of radiation-induced diseases. This information provides major positive reassurances about individual exposures and risk that will minimise the physical and psychological impact of wartime radiation exposures.

Review, Tutorial↗
NASA NTRS1997

Identification of defective illegitimate recombinational repair of oxidatively-induced DNA double-strand breaks in ataxia-telangiectasia cells

Ataxia-telangiectasia (A-T) is an autosomal-recessive lethal human disease. Homozygotes suffer from a number of neurological disorders, as well as very high cancer incidence. Heterozygotes may also have a higher than normal risk of cancer, particularly for the breast. The gene responsible for the disease (ATM) has been cloned, but its role in mechanisms of the disease remain unknown. Cellular A-T phenotypes, such as radiosensitivity and genomic instability, suggest that a deficiency in the repair of DNA double-strand breaks (DSBs) may be the primary defect; however, overall levels of DSB rejoining appear normal. We used the shuttle vector, pZ189, containing an oxidatively-induced DSB, to compare the integrity of DSB rejoining in one normal and two A-T fibroblast cells lines. Mutation frequencies were two-fold higher in A-T cells, and the mutational spectrum was different. The majority of the mutations found in all three cell lines were deletions (44-63%). The DNA sequence analysis indicated that 17 of the 17 plasmids with deletion mutations in normal cells occurred between short direct-repeat sequences (removing one of the repeats plus the intervening sequences), implicating illegitimate recombination in DSB rejoining. The combined data from both A-T cell lines showed that 21 of 24 deletions did not involve direct-repeats sequences, implicating a defect in the illegitimate recombination pathway. These findings suggest that the A-T gene product may either directly participate in illegitimate recombination or modulate the pathway. Regardless, this defect is likely to be important to a mechanistic understanding of this lethal disease.

Non-NASA Center↗
NASA NTRS2004

Dissemination of information about the technologies of the Vision Research Lab through the World Wide Web

The Vision Research Lab at NASA John Glenn Research Center is headed by Dr. Rafat Ansari. Dr. Ansari and other researchers have developed technologies that primarily use laser and fiber optics to non-invasively detect different ailments and diseases of the eye. One of my goals as a LERCIP intern and ACCESS scholar for the 2004 summer is to inform other NASA employees, researchers and the general public about these technologies through the development of a website. The website incorporates the theme that the eye is a window to the body. Thus by investigating the processes of the eye, we can better understand and diagnosis different ailments and diseases. These ailments occur in not only earth bound humans, but astronauts as well as a result of exposure to elevated levels of radiation and microgravity conditions. Thus the technologies being developed at the Vision Research Lab are invaluable to humans on Earth in addition to those astronauts in space. One of my first goals was to research the technologies being developed at the lab. The first several days were spent immersing myself in the various articles, journals and reports about the theories behind Dynamic Light Scattering, Laser Doppler Flowmetry, Autofluoresence, Raman Spectroscopy, Polarimetry and Oximetry. Interviews with the other researchers proved invaluable to help understand these theories as well gain hands on experience with the devices being developed using these technologies. The rest of the Vision Research Team and I sat down and discussed how the overall website should be presented. Combining this information with the knowledge of the theories and applications of the hardware being developed, I worked out different ideas to present this information. I quickly learned Paint Shop Pro 8 and FrontPage 2002, as well as using online tutorials and other resources to help design an effective website. The Vision Research Lab website incorporates the anatomy and physiology of the eye, different diseases that affect the eye and the technologies being develop at the lab to help diagnosis these diseases. It also includes background information on Dr. Ansari as well as other researchers involved in the lab and it includes segments on patents, awards and achievements. There are links to help viewers navigate to internal and external websites to further investigate different ideas and hrther understand the implications of these technologies at being developed.

Dorais, Christopher M.↗
NASA NTRS2004

Regulation of Vascular Growth in the Chorioallantoic Membrane of Japanese Quail Eggs

The Microgravity Research Program is part of NASA's Office of Biological and Physical Research (OBPR). The mission of the Microgravity Fluid Physics research program is to facilitate and conduct the best possible fluid physics research using the space environment and make this knowledge available to the scientific community and the public at large. During the summer of 2004, I worked in this division with Dr. Patricia Parsons-Wingerter. Dr. Parsons was working on several projects that used the chorioallantoic membrane (CAM) of Japanese quail eggs. The CAM develops in the eggs of birds and reptiles and is a very vascular fetal membrane composed of the fused chorion and adjacent wall of the allantois. The CAM is formed on day 4 of incubation and its primary job is to mediate gas exchanges with the extra embryonic environment. The CAM of our Japanese quail eggs is easily identifiable to us because it is transparent and it sits on top of the yolk with the embryo in the center. The CAM is of interest because of its many applications in the field of medicine as it relates to vascular remodeling and angiogenesis. Angiogenesis is simply the growth or formation of new blood vessels and anti-angiogenesis is the inhibition of said vessels. Angiogenesis occurs naturally in a healthy body for healing wounds and for restoring blood flow to tissues after injury and in females during the monthly reproductive cycle. In many serious diseases, like several types of cancer and those that affect the heart and cardiovascular system, the body loses control over angiogenesis. These diseases, which are dependent on angiogenesis, result when new blood vessels either grow excessively or insufficiently. The chorioallantoic membrane of our Japanese quail eggs gives a good model of angiogenesis. We used angiogenic regulators to inhibit or stimulate vascular growth in the CAM in a healthy manner and they induced distinct vascular patterns in vivo. Certain dominant regulators can be recognized by their unique vascular patterns and from these patterns; we can deduce specific alterations in vascular remodeling and angiogenesis. This will aid us in early-stage diagnosis and customized therapies for patients with angiogenic-dependent diseases. This particular research is important to NASA because cardiovascular health issues are the second highest of ten categories that have been defined as risk factors in human space exploration. Also, cardiovascular-related diseases have been the leading cause of death in America since 1981. Therefore, this kind of research in the field of cardiovascular health is of great importance to humans on earth and in space. This particular research is important to NASA because cardiovascular health is of great importance to humans on earth and in space.

Montague, Idoreyin P.↗
NASA NTRS2010

Filovirus Research: The Need for an Integrated Approach in Time and Space

The episodic appearance of Ebola virus (EBOV) and Marburg virus (MARV) across central Africa over the last 15 years not only underscores the importance of filoviruses as uniquely virulent agents to both human and wildlife communities but also implies a very complex transmission scenario that must be understood if we are to prevent or mitigate filovirus outbreaks in the future. Efforts of a global network of scientists and healthcare workers have expanded our knowledge of filoviruses to meet the growing threat of Ebola and Marburg hemorrhagic fevers in Africa. In recent decades, several newly emerging diseases have resulted in major threats to both affected communities and global public health. Viruses from wildlife hosts in particular, have exhibited a capability for cross-species transmission (CST), and have caused high-impact diseases in humans Such as Ebola and Marburg hemorrhagic fevers, Nipah and severe acute respiratory syndrome (SAILS). It has been estimated that about 60.3% (Jones et al. 2008) of human infectious diseases are of animal origin (zoonoses) and even some important viral diseases that are traditionally considered of human origin, for example measles and smallpox, may very well have their prehistoric origins in wildlife (Wolfe et al 2007). It maybe logical and prudent therefore, to anticipate that there are other, new filoviruses out there that will cross into humans at some point in time. If we anticipate that these will happen and wish to be prepared for and mitigate this potential, then an understanding of filoviruses as a biologic system in the environment will be essential to that process. We will need to know how the ecological dynamic of CST interacts with a 'new' viruse's evolutionary factors to overcome environmental, demographic and host-specific barriers to transmission and infectivity to humans.

Pinzon, Jorge E.↗
NASA NTRS2011

A Monitoring System for Crimean Congo Hemorrhagic Fever Epidemiology Studies in Afghanistan

In the last few years, tick-borne diseases have been reported as a resurging in the Middle East. Crimean-Congo hemorrhagic fever (CCHF) is endemic in the Middle East, including Turkey, Iran, Afghanistan and Pakistan. Recent studies have explored the causal link between environmental and disease incidence patterns by correlating remote sensing indicators (surface temperature, rainfall, and vegetation indices of plant photosynthetic activity) with spatially explicit epidemiological data. We combined the monitoring of environmental data at monthly temporal resolutions with available reports of confirmed CCHF cases to identify the environmental properties of endemic regions and quantify those properties to CCHF risk. We also conducted a sero-prevalence survey in a sample of households (human and animal specimens) in 9 villages in Engil district surrounding Herat province, in western Afghanistan. We present analysis results from our study villages and validate the associated environmental conditions as predictive for human disease occurrences. Risk prediction is critical for anticipating the type and potential impact of disease threats for timely response action.

Mustafa, M.↗
NASA NTRS2010

Flight Crew Health Stabilization Program

This document establishes the policy and procedures for the HSP and is authorized through the Director, Johnson Space Center (JSC). This document delineates the medical operations requirements for the HSP. The HSP goals are accomplished through an awareness campaign and procedures such as limiting access to flight crewmembers, medical screening, and controlling flight crewmember activities. NASA's Human Space Flight Program uses strategic risk mitigation to achieve mission success while protecting crew health and safety. Infectious diseases can compromise crew health and mission success, especially in the immediate preflight period. The primary purpose of the Flight Crew Health Stabilization Program (HSP) is to mitigate the risk of occurrence of infectious disease among astronaut flight crews in the immediate preflight period. Infectious diseases are contracted through direct person-to-person contact, and through contact with infectious material in the environment. The HSP establishes several controls to minimize crew exposure to infectious agents. The HSP provides a quarantine environment for the crew that minimizes contact with potentially infectious material. The HSP also limits the number of individuals who come in close contact with the crew. The infection-carrying potential of these primary contacts (PCs) is minimized by educating them in ways to avoid infections and avoiding contact with the crew if they are or may be sick. The transmission of some infectious diseases can be greatly curtailed by vaccinations. PCs are strongly encouraged to maintain updated vaccinations.

Johnston, Smith L.↗
NASA NTRS2013

Rapid Detection of Herpes Viruses for Clinical Applications

There are eight herpes viruses that infect humans, causing a wide range of diseases resulting in considerable morbidity and associated costs. Varicella zoster virus (VZV) is a human herpes virus that causes chickenpox in children and shingles in adults. Approximately 1,000,000 new cases of shingles occur each year; post-herpetic neuralgia (PHN) follows shingles in 100,000 to 200,000 people annually. PHN is characterized by debilitating, nearly unbearable pain for weeks, months, and even years. The onset of shingles is characterized by pain, followed by the zoster rash, leading to blisters and severe pain. The problem is that in the early stages, shingles can be difficult to diagnose; chickenpox in adults can be equally difficult to diagnose. As a result, both diseases can be misdiagnosed (false positive/negative). A molecular assay has been adapted for use in diagnosing VZV diseases. The polymerase chain reaction (PCR) assay is a non-invasive, rapid, sensitive, and highly specific method for VZV DNA detection. It provides unequivocal results and can effectively end misdiagnoses. This is an approximately two-hour assay that allows unequivocal diagnosis and rapid antiviral drug intervention. It has been demonstrated that rapid intervention can prevent full development of the disease, resulting in reduced likelihood of PHN. The technology was extended to shingles patients and demonstrated that VZV is shed in saliva and blood of all shingles patients. The amount of VZV in saliva parallels the medical outcome.

Pierson, Duane↗
NASA NTRS2015

2014 Space Radiation Standing Review Panel

The 2014 Space Radiation Standing Review Panel (from here on referred to as the SRP) participated in a WebEx/teleconference with members of the Space Radiation Program Element, representatives from the Human Research Program (HRP), the National Space Biomedical Research Institute (NSBRI), and NASA Headquarters on November 21, 2014 (list of participants is in Section XI of this report). The SRP reviewed the updated Research Plan for the Risk of Cardiovascular Disease and Other Degenerative Tissue Effects from Radiation Exposure (Degen Risk). The SRP also received a status update on the Risk of Acute and Late Central Nervous System Effects from Radiation Exposure (CNS Risk), the Risk of Acute Radiation Syndromes Due to Solar Particle Events (ARS Risk), and the Risk of Radiation Carcinogenesis (Cancer Risk). The SRP thought the teleconference was very informative and that the Space Radiation Program Element did a great job of outlining where the Element is with respect to our state of knowledge on the risks of carcinogenesis, central nervous system effects, and the risk of cardiovascular disease and other degenerative tissue effects from exposure to space radiation. The SRP was impressed with the quality of research that is being conducted and the progress the Space Radiation Program Element has made in the past year. While much work has been done, the SRP had a few remaining questions regarding the broad applicability of these findings to a manned deep space mission (in terms of cognitive function, the paradigms were still hippocampal based and also using Alzheimer disease models). The SRP believes that NASA should consider developing an approach to follow astronauts long-term (beyond retirement) for potential side-effects/risks of space exposure that may be unknown. Radiation toxicities often occur decades after exposure, and potential consequences would be missed if intensified exams stop after retirement of the astronauts. In addition, while cancer is one consequence of radiation exposure that is monitored, potential other side effects (CNS, Alzheimer Disease, loss of cognitive function, etc.) are not included in long-term studies and would be missed. Inclusion of long-term data would be of benefit to the astronauts themselves who have given their service to the corps but also to future astronauts and the future of space exploration.

Steinberg, Susan↗
NASA NTRS2016

Evaluation of Different MODIS AOD Retrieval Algorithms for PM (sub 2.5) Estimation in the Western, Midwestern and Southeastern United States with Implications for Public Health

This study was part of the research activities of the Center for Applied Atmospheric Research and Education (CAARE) funded by the NASA MUREP (Minority University Research and Education Project) Institutional Research Opportunity (MIRO) Program. Satellite measurements of Aerosol Optical Depth (AOD) have been shown to be correlated with ground measurements of fine particulate matter less than 2.5 microns PM (sub 2.5), which in turn has been linked to respiratory and heart diseases. The strength of the correlation between AOD and PM (sub 2.5) varies for different AOD retrieval algorithms and geographic regions. We evaluated several Moderate Resolution Imaging Spectrometer (MODIS) AOD products from different satellites (Aqua vs. Terra), retrieval algorithms (Dark Target versus Deep Blue), Collections (5.1 versus 6) and spatial resolutions (10-kilometers versus 3-kilometers) for cities in the Western, Midwestern and Southeastern U.S. We developed and validated PM (sub 2.5) prediction models using remotely-sensed AOD data, which were improved by incorporating meteorological variables (temperature, relative humidity, precipitation, wind speed, and wind direction) from the North American Land Data Assimilation System Phase 2 (NLDAS-2). Adding these meteorological data significantly improved the predictive power of all the PM (sub 2.5) models, especially in the Western U.S. Temperature, relative humidity and wind speed were the most significant meteorological variables throughout the year in the Western U.S. Wind speed was the most significant meteorological variable for the cold season while temperature was the most significant variable for the warm season in the Midwestern and Southeastern U.S. Our study re-establishes the connection between PM (sub 2.5) and public health concerns including respiratory and cardiovascular diseases (asthma, high blood pressure, coronary heart disease, heart attack, and stroke). Using PM (sub 2.5) data and health data from the Centers for Disease Control and Prevention (CDC)'s Behavioral Risk Factor Surveillance System (BRFSS), our statistical analysis showed that heart attack and stroke occurrences had the strongest correlations with PM (sub 2.5).

Environmental Public Health↗
NASA NTRSDate not supplied

SPACEFLIGHT-INDUCED CHANGES IN MICROBIAL VIRULENCE AND THE IMPACT TO THE HOST IMMUNE RESPONSE

INTRODUCTION Over the past 50 years, microorganisms have displayed unexpected responses relevant to infectious disease when grown in microgravity and microgravity analogue environments, including changes in final cell concentration, biofilm production, stress resistance, antibiotic sensitivity, gene expression, and virulence. In parallel, astronaut studies have characterized a persistent spaceflight-induced dysregulation of the human immune system; consisting of altered leukocyte distribution, reductions in T and NK cell function, altered cytokine profiles, and reactivation of latent herpesviruses. Further, astronauts have some degree of clinical incidence, primarily infectious disease episodes and atopic dermatitis. The impact of the microgravity environment on host-pathogen interactions and potential for clinical disease remains understudied and poorly characterized. SPECIFIC AIMS In the Host-Microorganism, Microbial Response aspect of this study, the following Specific Aims are being investigated, using the microbial pathogens, Salmonella enterica Enteritidis, Pseudomonas aeruginosa, Burkholderia cepacia, Streptococcus pneumoniae, and enterohemorrhagic Escherichia coli. Aim 1: Characterize the effect of spaceflight analogue culture on microbial pathogenesis-related stress responses and in vitro host-pathogen interactions. Analysis will include microbial stress responses as well as colonization and viability following pathogen challenge of three-dimensional (3-D) tissue co-culture models containing immune cells. We specifically selected obligate and opportunistic pathogens that are medically important and have been or are likely to be found aboard spacecraft. Aim 2: Characterize the effect of spaceflight analogue culture on the virulence potential of pathogenic microorganisms. Changes in virulence will be assessed using a mouse model of infection. SIGNIFICANCE The goal of this study is to use spaceflight analogue conditions to gain insight into the breadth of medically-significant International Space Station microorganisms that have altered virulence and the impact of those changes on the immune response of the host, including astronaut immune cells. This information will provide critical understanding into the impact of microgravity on potential alterations in microbial virulence and associated infectious disease risk to crew health during spaceflight missions.

C. M. Ott↗
NASA NTRSDate not supplied

Watching Without Seeing a Tool to Surveil Astronaut Health Outcomes While Maintaining Astronaut Medical Privacy

BACKGROUND The Privacy Act of 1974 regulates the use a nd disclosure of personally identifiable information by US Federal agencies. The Act applies to biographical, financial, a nd other identity-linked information, a s well a s personal health information (PHI). As such, the use of astronaut PHI is limited to authorized personnel for preapproved uses, with data reporting often limited to aggregated information about groups. These limitations on the use a nd reporting of astronaut PHI complicates surveillance efforts, wherein epidemiologists a t the National Aeronautics and Space Administration (NASA)monitor the incidence of targeted health conditions in the astronaut population, or to discover emerging trends of aging and disease. Stratification on one or more covariates –particularly time-period, sex, a nd mission participation –can lead to extremely small datasets such that the reporting of results is potentially attributable to individuals. An additional challenge is the small size of the astronaut population, both in terms of numbers of individuals a s well a s in terms of density of exposure time. Such small datasets yield volatile rate estimates that are difficult to interpret. To a id the epidemiological surveillance efforts, a surveillance tool is required that can (a) satisfy the need for rapid computation of condition-specific incidence and mortality rates; (b) improve the statistical estimates of these estimated rates; and (c) maintain astronaut privacy. Here we describe a nd demonstrate such a tool. METHODS We devised a system that models incidence a nd mortality rates rather than calculating them directly. This ha s the advantage of using all the available data to derive the estimates, lea ding to rates that a re not attributable to any one individual, a nd a re a s numerically stable a s they can be given the extremely limited data. The system models disease endpoints using a Poisson regression model with exposure density (measured in person-years) a s a n offset term. By doing so the model is estimating event counts per person-year, equivalent to modeling the rates directly. It uses a standard (pre-specified)set of covariates; the system does not engage in “model-building” as model parsimony is not the goa l. Instead, it is explicitly recognized that if a covariate is not statistically significant a nd not a confounder then it will likely have very little effect on the estimate of the incidence a nd mortality rates. Users are able to specify the disease endpoint of interest and the covariates over which they would like to stratify. The system then uses the resulting model to compute the estimated rates for the user-chosen configuration of variables as visualizes those either over an age range within a specified time-period, or over time for astronauts with a specified age range. RESULTS The first iteration of the tool computes incidence a nd mortality rates for cardiovascular conditions and cancers. Code ha s been developed to retrieve the appropriate data from the IMPALA analysis platform, compute the models for incidence a nd mortality, a nd then use those models to generate the corresponding rate curves. A companion graphical user interface allows the user to specify the curves and visualize the results. CONCLUSIONS It is important to note that the rapid surveillance tool described here is neither meant to be a definitive assessment of the incidence or mortality of any particular disease or condition in the astronaut population, nor is it meant to be used for research purposes. Rather, it is meant as an early indicator that in-depth investigation may be warranted. By automating a repetitive process and leveraging carefully curated astronaut health outcomes, the tool makes possible a rapid “first look” into known areas of concern, and, if used judiciously, may surface new areas of concern for long-term astronaut health. This work is supported in part by the Translational Research Institute for Space Health (TRISH) through NASA Cooperative Agreement NNX16AO69A.

R J Reynolds↗
NASA NTRSDate not supplied

Deciphering Spaceflight Medical Risks Using High-Performance Computing and Next Generation Sequencing Data From Model Organisms

Somatic mutations are acquired point mutations and other forms of genetic alteration in the DNA of somatic cells in the body. Unlike germline mutations, which can be passed on from one individual to another, somatic mutations are not heritable. Somatic mutation (also called genetic sequence variation) has been recognized for decades as an important mechanism for initiating the development of cancer. Now, with the advent of next generation sequencing (NGS), the study of somatic mutation has become much more accessible, enabling genome scientists to characterize somatic mutations in a comprehensive fashion across the entire genome. From recent studies, it is now apparent that other disease processes besides cancer may be influenced by somatic mutation as well, including degenerative processes and inflammatory diseases. Cancer, degenerative diseases and inflammatory processes are all of concern in the setting of spaceflight. Study of somatic mutation analysis, therefore, is an important new tool for examining some of the earliest changes in the genome that lead to disease. This approach has tremendous potential for NASA, for analysis of both model organisms and humans.

Somatic mutation on ISS↗