Biostatistics of Space Exploration - Microbiology and Sterilization
Contamination probability distribution models for spacecraft - microbiological assays and sterilization of spacecraft components
MICROBIOLOGY↗
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Biostatistics and space exploration - Microbiology and sterilization
Statistical models for spacecraft sterilization and microbial growths
Cornell, R. G.↗
Biostatistics of space exploration - Microbiology and sterilization Final report, 1 Sep. 1965 - 1 Sep. 1970
Statistical procedures for investigating decontamination of spacecraft and microbial assays
Cornell, R. G.↗
Differences in Pre and Post Vascular Patterning of Retinas from ISS Crew Members and HDT Subjects by VESGEN Analysis
Accelerated research by NASA [1] has investigated the significant risks for visual and ocular impairments Spaceflight Associated Neuro-Ocular Syndrome /Visual Impairment/Intracranial Pressure (SANS/VIIP) incurred by microgravity spaceflight, especially long-duration missions. Our study investigates the role of blood vessels in the incidence and etiology of SANS/VIIP within the retinas of Astronaut crewmembers pre-and post-flight to the International Space Station (ISS) by NASA's VESsel GENeration Analysis (VESGEN). The response of retinal vessels in crewmembers to microgravity was compared to that of retinal vessels to Head-Down Tilt (HDT) in subjects undergoing 70-Day Bed Rest. The study tests the proposed hypothesis that cephalad fluid shifts missions, resulting in ocular and visual impairments, are necessarily mediated in part by retinal blood vessels, and are therefore accompanied by significant remodeling of retinal vasculature.Vascular patterns in the retinas of crew members and HDTBR subjects extracted from 30° infrared (IR) Heidelberg Spectralis® images collected pre/postflight and pre/post HDTBR, respectively, were analyzed by VESGEN (patent pending). a mature, automated software developed as a research discovery tool for progressive vascular diseases in the retina and other tissues [2]. The weighted, multi-parametric VESGEN analysis generates maps of branching arterial and venous trees and quantification by parameters such as the fractal dimension (Df, a modern measure of vascular space-filling capacity), vessel diameters, and densities of vessel length and number classified into specific branching generations by vascular physiological branching rules [2,3]. The retrospective study approved by NASA’s Institutional Review Board included six HDT subjects (NASA Flight Analogs Research Unit [FARU] Campaign 11; for example, [4]) and eight ISS crewmembers monitored by routine occupational surveillance who provided their study consents to NASA’s Lifetime Surveillance of Astronaut Health (LSAH). For the initial blinded VESGEN phase, ophthalmic retinal images were masked as to subject identity and pre- and post-status. In the second unblinded phase, VESGEN results were analyzed according to the pre- and post-status of left and right retinas matched to each subject. To complete our study, vascular results will be subjected to NASA biostatistical analysis and correlated with other ophthalmic and medical findings. Preliminary results for changes in the pre- to post-status of vascular patterning in the retinas of crewmembers and HDT subjects are strikingly opposite. By Df and other vascular branching measures, the space-filling capacity of arterial and venous trees decreased in a substantial subset of crewmembers (11/16 retinas). In contrast, vascular densities increased in a substantial subset of HDT subjects by the same parameters (6/10 retinas, currently excluding one anomalous subject). To conclude the study, biostatistical and medical analyses will be of critical importance for investigating the validity of these vascular findings. Vascular densities appeared to decrease in the retinas of crewmembers following ISS Missions, and increase in subjects after HDT. The vascular increases and decreases most likely derive primarily from limits of resolution to the ophthalmic imaging that does not capture the smallest vessels, rather than from vessel growth or atrophy. Differences in arterial and venous response to cephalad fluid shifts induced by ISS and HDT may have resulted from a long-duration conditioning phenomenon (for example, 6-month ISS missions compared to 70-day HDT), or the presence of gravity in HDT compared to microgravity onboard the ISS. To conclude our study, the biostatistical and medical analyses will be of critical importance for investigating the validity and significance of the VESGEN findings.
Murray, M. C.↗
An integrative approach to space-flight physiology using systems analysis and mathematical simulation
An approach was developed to aid in the integration of many of the biomedical findings of space flight, using systems analysis. The mathematical tools used in accomplishing this task include an automated data base, a biostatistical and data analysis system, and a wide variety of mathematical simulation models of physiological systems. A keystone of this effort was the evaluation of physiological hypotheses using the simulation models and the prediction of the consequences of these hypotheses on many physiological quantities, some of which were not amenable to direct measurement. This approach led to improvements in the model, refinements of the hypotheses, a tentative integrated hypothesis for adaptation to weightlessness, and specific recommendations for new flight experiments.
Leonard, J. I.↗
An Integrated Analysis of the Physiological Effects of Space Flight: Executive Summary
A large array of models were applied in a unified manner to solve problems in space flight physiology. Mathematical simulation was used as an alternative way of looking at physiological systems and maximizing the yield from previous space flight experiments. A medical data analysis system was created which consist of an automated data base, a computerized biostatistical and data analysis system, and a set of simulation models of physiological systems. Five basic models were employed: (1) a pulsatile cardiovascular model; (2) a respiratory model; (3) a thermoregulatory model; (4) a circulatory, fluid, and electrolyte balance model; and (5) an erythropoiesis regulatory model. Algorithms were provided to perform routine statistical tests, multivariate analysis, nonlinear regression analysis, and autocorrelation analysis. Special purpose programs were prepared for rank correlation, factor analysis, and the integration of the metabolic balance data.
Leonard, J. I.↗
Logistic Risk Model for the Unique Effects of Inherent Aerobic Capacity on (+)G(sub z) Tolerance Before and After Simulated Weightlessness
Small sample size (n less than 1O) and inappropriate analysis of multivariate data have hindered previous attempts to describe which physiologic and demographic variables are most important in determining how long humans can tolerate acceleration. Data from previous centrifuge studies conducted at NASA/Ames Research Center, utilizing a 7-14 d bed rest protocol to simulate weightlessness, were included in the current investigation. After review, data on 25 women and 22 men were available for analysis. Study variables included gender, age, weight, height, percent body fat, resting heart rate, mean arterial pressure, Vo(sub 2)max and plasma volume. Since the dependent variable was time to greyout (failure), two contemporary biostatistical modeling procedures (proportional hazard and logistic discriminant function) were used to estimate risk, given a particular subject's profile. After adjusting for pro-bed-rest tolerance time, none of the profile variables remained in the risk equation for post-bed-rest tolerance greyout. However, prior to bed rest, risk of greyout could be predicted with 91% accuracy. All of the profile variables except weight, MAP, and those related to inherent aerobic capacity (Vo(sub 2)max, percent body fat, resting heart rate) entered the risk equation for pro-bed-rest greyout. A cross-validation using 24 new subjects indicated a very stable model for risk prediction, accurate within 5% of the original equation. The result for the inherent fitness variables is significant in that a consensus as to whether an increased aerobic capacity is beneficial or detrimental has not been satisfactorily established. We conclude that tolerance to +Gz acceleration before and after simulated weightlessness is independent of inherent aerobic fitness.
Ludwig, David A.↗
A National Virtual Specimen Database for Early Cancer Detection
Access to biospecimens is essential for enabling cancer biomarker discovery. The National Cancer Institute's (NCI) Early Detection Research Network (EDRN) comprises and integrates a large number of laboratories into a network in order to establish a collaborative scientific environment to discover and validate disease markers. The diversity of both the institutions and the collaborative focus has created the need for establishing cross-disciplinary teams focused on integrating expertise in biomedical research, computational and biostatistics, and computer science. Given the collaborative design of the network, the EDRN needed an informatics infrastructure. The Fred Hutchinson Cancer Research Center, the National Cancer Institute,and NASA's Jet Propulsion Laboratory (JPL) teamed up to build an informatics infrastructure creating a collaborative, science-driven research environment despite the geographic and morphology differences of the information systems that existed within the diverse network. EDRN investigators identified the need to share biospecimen data captured across the country managed in disparate databases. As a result, the informatics team initiated an effort to create a virtual tissue database whereby scientists could search and locate details about specimens located at collaborating laboratories. Each database, however, was locally implemented and integrated into collection processes and methods unique to each institution. This meant that efforts to integrate databases needed to be done in a manner that did not require redesign or re-implementation of existing system
distributed↗
Informal Statistics Help Desk
Back by popular demand, the JSC Biostatistics Lab is offering an opportunity for informal conversation about challenges you may have encountered with issues of experimental design, analysis, data visualization or related topics. Get answers to common questions about sample size, repeated measures, violation of distributional assumptions, missing data, multiple testing, time-to-event data, when to trust the results of your analyses (reproducibility issues) and more.
Ploutz-Snyder, R. J.↗
Informal Statistics Help Desk
Back by popular demand, the JSC Biostatistics Laboratory and LSAH statisticians are offering an opportunity to discuss your statistical challenges and needs. Take the opportunity to meet the individuals offering expert statistical support to the JSC community. Join us for an informal conversation about any questions you may have encountered with issues of experimental design, analysis, or data visualization. Get answers to common questions about sample size, repeated measures, statistical assumptions, missing data, multiple testing, time-to-event data, and when to trust the results of your analyses.
Young, M.↗
Differences in Pre and Post Vascular Patterning Within Retinas from ISS Crew Members and Head-Down Tilt (HDT) Subjects by VESGEN Analysis
Accelerated research by NASA has investigated the significant risks incurred during long-duration missions in microgravity for Space Flight-Associated Neuro-ocular Syndrome (SANS, formerly known as Visual Impairments associated with Increased Intracranial Pressure, VIIP) [1]. For our study, NASA's VESsel GENeration Analysis (VESGEN) was used to investigate the role of retinal blood vessels in the etiology of SANS/VIIP. The response of retinal vessels to microgravity was evaluated in astronaut crew members pre and post flight to the International Space Station (ISS), and compared to the response of retinal vessels in healthy volunteers to 6deg head-down tilt during 70 days of bed rest (HDTBR). For the study, we are testing the hypothesis that long-term cephalad fluid shifts resulting in ocular and visual impairments are necessarily mediated in part by retinal blood vessels, and therefore are accompanied by structural adaptations of the vessels. METHODS: Vascular patterns in the retinas of crew members and HDTBR subjects extracted from 30deg infrared (IR) Heidelberg Spectralis images collected pre/postflight and pre/post HDTBR, respectively, were analyzed by VESGEN (patent pending). VESGEN is a mature, automated software developed as a research discovery tool for progressive vascular diseases in the retina and other tissues. The multi-parametric VESGEN analysis generates maps of branching arterial and venous trees quantified by parameters such as the fractal dimension (Df, a modern measure of vascular space-filling capacity), vessel diameters, and densities of vessel length and number classified into specific branching generations according to vascular physiological branching rules. The retrospective study approved by NASA's Institutional Review Board included the analysis of bilateral retinas in eight ISS crew members monitored by routine occupational surveillance and six HDTBR subjects (NASA FARU Campaign 11, for example). The VESGEN analysis was conducted in a blinded fashion, with IR retinal images masked to the subject's identity, ophthalmic and clinical characteristics, and to the temporal sequence of image collection. To complete our study, VESGEN results will be analyzed statistically and correlated with other ophthalmic and medical findings. RESULTS: Preliminary results for changes in the pre to post status of vascular patterning in the retinas of crew members and HDTBR subjects are interestingly opposite. By Df and other vascular branching measures, the space-filling capacity of arterial and venous trees decreased in the majority of crew members (11/16 retinas). In contrast, vascular densities increased in HDTBR subjects by the same parameters (6/10 retinas). To conclude the study, biostatistics and medical analyses will be conducted to quantify and draw conclusions about how the changes associated with flight compare to those associated with HDTBR. CONCLUSIONS: Vascular densities appeared to decrease in the retinas of ISS crew members and increase in HDTBR subjects. Differences in arterial and venous response to cephalad fluid shifts induced by ISS and HDTBR may have resulted from a long-duration conditioning phenomenon (for example, 6-month ISS missions compared to 70 days HDTBR), or the presence of gravity in HDTBR compared to microgravity on the ISS. In addition, increased and decreased vessel diameters for Crew Members and HDTBR, respectively, are subject to limits of im
Vascular↗
Crowd Sourcing Medical Data Collection Using Medical Students
OBJECTIVE We undertook an upgrade of the Evidence Library database of NASA HRP’s Integrated Medical Model, assessing 120 medical conditions which integrate with a novel probabilistic risk assessment (IMPACT) tool of medical risk and resource utilization for long duration exploration human spaceflight. This data collection process included a selection of these conditions crowd sourced over one year via three 4-week medical student electives at the University of Colorado School of Medicine (IDPT 8059 Space Medicine: Human Spaceflight Factors & Medical Risk Assessment). Students undertook a rapid systematic review of each medical condition, under close preceptors with backgrounds in clinical medicine, library science, epidemiology, biostatistics, and evidence-based medicine. As part of the elective, students also received instruction in core space medicine concepts, evidence based medicine and problem based learning sessions as a flight surgeon supporting a simulated Mars mission. METHODS The list of 120 medical conditions includes both common, terrestrial illness/injury (epistaxis, diverticulitis) as well as spaceflight-specific ones (space adaptation conditions, EVA-related injuries). A rapid systematic review process was developed that would allow students to find the data for determining disease incidence/prevalence, return to definitive care (often a surrogate such as hospitalization rates), loss of crew life, and treatment duration. Each data point required a tailored, specialized search process using different databases and corresponding specialized search filters. Databases were selected on their ability to provide high quality literature in an efficient manner and prioritized by their ability to provide graded evidence via a set rubrics specific to human spaceflight. Students were responsible for performing all literature searches and identifying the highest quality available evidence for each data point. Completed student data sheets underwent initial review by faculty preceptors followed by a secondary editing review by the ExMC Clinical Science Team. RESULTS Over the course of three electives, approximately 105 medical conditions were researched by students using spreadsheets with pre-crafted search strategies. Overall, this process was successful in allowing students to perform the preponderance of work to update incidence, treatment duration, return to definitive care, and loss of crew life data points. Students were successful in running searches, identifying the necessary data points within the literature, and determining the types of terrestrial data that most aligns with the astronaut population for successful completion of their tasks. Limitations included variable student experience with search methodologies [PubMed], differing values of evidence grading [best practice evidence based medicine vs. relevant to spaceflight], and students’ unfamiliarity with spaceflight specific conditions. CONCLUSION Finding the relevant literature for medical conditions in spaceflight within terrestrial databases in a systematic method is time consuming and not intuitive. However, the stepwise process that balanced sensitivity with specificity allowed for students to be highly successful in a short amount of time. Additionally, as the process was refined over the course of three electives, preceptors were better able to anticipate where students were likely to encounter barriers, which allowed the course to be adjusted to account for certain data points needing more time for completion. This replicable process may be an efficient way to accomplish rapid systematic reviews for a large volume of data in a short amount of time.
J Lemery↗
Overview of the Inaugural Space Health Impacts for the NASA Experience (SHINE) Training Program – Virtual Space Radiation Curriculum
The Space Radiation Element part of NASA Human Research Program initiated a virtual, annual space radiation curriculum. The SHINE space radiation curriculum aims to educate participants not only in the scientific aspects of space radiation but also in the agency’s risk management strategies. SHINE combines weekly seminars by speakers from NASA, other government agencies, academia, and industry, with networking sessions designed to foster collaboration between participants and interactions with NASA scientists. A total of 59 applications were received from which 25 participants were selected. The 25 participants, with citizenship from a total of 8 countries, are composed of 5 graduate students, 4 postdocs, 11 scientists and 5 professors/medical doctors. Participants have a wide range of expertise including molecular and cellular biology, microbiology, botany, physiology, engineering, physics, aerospace medicine, planetary science, biostatistics, and modeling. The inaugural course ran weekly from February 2023 to August 2023 and was comprised of lectures, less formal coffee hours and office hours. The topics covered ranged from space environments to health effects to granting opportunities. The second annual SHINE training program is scheduled from February to August 2024. In addition, a separate competitive practicum session, to allow participants to gain hands-on radiation experience, will be held Fall 2024 at the NASA Space Radiation Laboratory (NSRL).
Janice A. Zawask↗
Overview of The Inaugural Space Health Impacts for the NASA Experience (SHINE) Training Program – Virtual Space Radiation Curriculum
The Space Radiation Element of the NASA Human Research Program initiated a virtual, annual space radiation curriculum. The Space Health Impacts for the NASA Experience (SHINE) space radiation didactic curriculum aims to educate participants not only in the scientific aspects of space radiation but also in the agency’s risk management strategies. SHINE combines weekly seminars by speakers from NASA, other government agencies, academia, and industry, with networking sessions designed to foster collaboration between participants and interactions with NASA scientists and HRP funded investigators. The inaugural course ran weekly from February 2023 to August 2023 and was comprised of lectures, less formal coffee hours and office hours. The SHINE topics ranged from space environments to health effects and countermeasure to granting opportunities. Participants developed beam time proposals for real, proposed, or potential experiments at the NASA Space Radiation Laboratory (NSRL) at the Brookhaven National Laboratory. For the 2023 course, a total of 59 applications were received from which 25 participants were selected. Selected participants were citizens from 8 countries and comprised 5 graduate students, 4 postdocs, 11 scientists and 5 professors/medical doctors. Participants had a wide range of expertise including molecular and cellular biology, microbiology, botany, physiology, engineering, physics, aerospace medicine, planetary science, biostatistics, and modeling. The second annual SHINE training program is scheduled from February to August 2024. In addition, a separate SHINE space radiation practicum session, to allow participants to gain hands-on radiation experience, will be held Fall 2024 at the NSRL.
Radiation↗
Overview of The Inaugural Space Health Impacts for the NASA Experience (SHINE) Training Program - Virtual Space Radiation Curriculum
The Space Radiation Element part of NASA Human Research Program initiated a virtual, annual space radiation curriculum. The SHINE space radiation curriculum aims to educate participants not only in the scientific aspects of space radiation but also in the agency’s risk management strategies. SHINE combines weekly seminars by speakers from NASA, other government agencies, academia, and industry, with networking sessions designed to foster collaboration between participants and interactions with NASA scientists. A total of 59 applications were received from which 25 participants were selected. The 25 participants, with citizenship from a total of 8 countries, are composed of 5 graduate students, 4 postdocs, 11 scientists and 5 professors/medical doctors. Participants have a wide range of expertise including molecular and cellular biology, microbiology, botany, physiology, engineering, physics, aerospace medicine, planetary science, biostatistics, and modeling. The inaugural course ran weekly from February 2023 to August 2023 and was comprised of lectures, less formal coffee hours and office hours. The topics covered ranged from space environments to health effects to granting opportunities. The second annual SHINE training program is scheduled from February to August 2024. In addition, a separate competitive practicum session, to allow participants to gain hands-on radiation experience, will be held Fall 2024 at the NASA Space Radiation Laboratory (NSRL).
SHINE↗
NASA's Space Health Impacts for the NASA Experience (SHINE) Training Program – Space Radiation Curriculum
In February 2023, the Space Radiation Element of the NASA Human Research Program initiated a virtual, annual space radiation curriculum. The Space Health Impacts for the NASA Experience (SHINE) Space Radiation Didactic Curriculum aims to educate participants not only in the scientific aspects of space radiation but also in the agency’s risk management strategies. SHINE Space Radiation Didactic Curriculum combined weekly seminars by speakers from NASA, other government agencies, academia, and industry, with networking sessions designed to foster collaboration between the competitively selected participants as well as interactions with NASA scientists and HRP funded investigators. The inaugural course ran weekly from February 2023 to August 2023 and was comprised of lectures, less formal coffee hours, and office hours. Each two-hour seminar sessions hosted 1-3 presentations on topics which ranged from the space radiation environment to health effects and countermeasure to granting opportunities. All lectures were recorded and will be published on the THREE (The Health Risks of Extraterrestrial Environments) website for public access (https://three.jsc.nasa.gov/). As a course requirement, participants developed individual or collaborative beam time proposals for real, proposed, or potential experiments at the NASA Space Radiation Laboratory (NSRL) at the Brookhaven National Laboratory. For the 2023 course, 25 participants were selected from a total of 59 applicants. Selected participants were citizens from 8 countries and comprised 5 graduate students, 4 postdocs, 11 scientists and 5 professors/medical doctors. Participants had a wide range of expertise including molecular and cellular biology, microbiology, botany, physiology, engineering, physics, aerospace medicine, planetary science, biostatistics, and modeling. The second annual SHINE training program is scheduled from February to August 2024. In addition, a separate SHINE Space Radiation Practicum session will be held in Fall 2024 at the NSRL. The SHINE Space Radiation Practicum is a unique opportunity that has not been available to the public since the closure of the NASA Space Radiation Summer School in 2017 and will allow a small cohort of participants competitively selected in Fall 2023 to gain hands-on radiation experience.
SHINE↗
Sensitivity Analysis of the Human Research Program’s Impact 1.0 Model
Sensitivity analysis estimates the relative contribution of the uncertainty in input values to the uncertainty of model outputs. Partial Rank Correlation Coefficient (PRCC) and Leave One Out (LOO) are methods of conducting sensitivity analysis on non-linear simulation models like the IMPACT Model. The PRCC method estimates the sensitivity using partial correlation of the ranks of the generated input values to each generated output value. The “partial” part is due to the adjustments made for the linear effects of all the other input values in the calculation of correlation between a particular input and each output. LOO removes a medical condition from test suite and calculates the change in the outcome. This is used to identify the influence of the condition input in the model The inputs to the sensitivity procedures include the number of occurrences of each of the one hundred plus IMPACT medical conditions generated over the simulations, and the IMPACT outputs from the MEDPRAT mathematical model. The outputs total task time lost (TTL), number of return to definitive care (RTDC), and number of loss of crew lives (LOCL). The IMPACT team will report the results of using PRCC and LOO on IMPACT 1.0. Tornado plots will assist in the visualization of the condition-related input sensitivities to each of the main outcomes. The outcomes of this sensitivity analysis will drive review focus by identifying conditions where changes in uncertainty, and input values could drive changes in overall model output uncertainty. These efforts are an integral part of the overall verification, validation, and credibility review of IMPACT 1.0.
Sensitivity Anaylsis↗
MULTI-OMICS STUDY OF THE EFFECT OF REDOX-ACTIVE METALLOPORPHYRIN ON MURINE RETINA DURING SPACEFLIGHT
Astronauts returning from spaceflight have experienced eye problems, which may decrease retinal performance and lead to long-term effects on visual acuity. This study leverages the collected data from spaceflown murine retinas that were treated with redox-active metalloporphyrin (BuOE) to mitigate spaceflight-induced changes and respective ground controls. 10-week-old adult C57BL/6 male mice (n=5 in each of BuOE treated and saline control groups for spaceflown and ground control samples) were flown on Space-X 24 to the ISS national lab, kept in low earth orbit for 35 days and returned to Earth alive. Our multi-omics analysis of RNA-sequencing and reduced representation bisulfite sequencing (RRBS) data generated from subsequent murine retina tissues uncovered genes, pathways, and epigenetic modifications consistent with therapeutic potential of BuOE. From RNA-Seq analysis of spaceflown murine samples, the treatment group show differentially expressed genes relative to saline controls that reached significance (adjusted p-value < 0.05) and included genes Gpx3 and Crhbp, which are related to protection against cell oxidative damage and cellular response to organonitrogen compounds. Ranked fold-changes from the same contrast were used for gene set enrichment analysis, which showed biological processes reaching significance (adjusted p-value < 0.05) including glutathione metabolic processes and cellular response to xenobiotic stimulus. RRBS data of the spaceflown murine samples found 139 hyper or hypo differentially methylated sites spread across chromosomes 1-19 (20% promoters, 21% exons, 43% introns | 20 CpG islands, 7 CpG shores) with a 10% methylation difference (q-value < 0.05).The findings from this investigation have the potential to provide valuable insights into the molecular mechanisms underlying conditions like spaceflight associated neuro-ocular syndrome and assess the effectiveness of BuOE as a countermeasure for astronauts experiencing neuro-ophthalmic abnormalities, which can lead to long-term effects on visual acuity.
Biostatistics↗