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NASA NTRS1994

Cosmic temperature fluctuations from two years of COBE differential microwave radiometers observations

The first two years of Cosmic Background Explorer (COBE) Differential Microwave Radiometers (DMR) observations of the cosmic microwave background (CMB) anisotropy are analyzed and compared with our previously published first year results. The results are consistent, but the addition of the second year of data increases the precision and accuracy detected CMB temperature fluctuations. The 2 yr 53 GHz data are characterized by rms temperature fluctuations of (delta-T)(sub rms) (7 deg) = 44 +/- 7 micro-K and (delta-T)(sub rms) (10 deg) = 30.5 +/- 2.7 micro-K at 7 deg and 10 deg angular resolution, respectively. The 53 x 90 GHz cross-correlation amplitude at zero lag is C(0)(sup 1/2) = 36 +/- 5 micro-K (68% CL) for the unsmoothed (7 deg resolution) DMR data. We perform a likelihood analysis of the cross-correlation function, with Monte Carlo simulations to infer biases of the method, for a power-law model of initial density fluctuations, P(k) proportional to R(exp n). The Monte Carlo simulations indicate that derived estimates of n are biased by +0.11 +/- 0.01, while the subset of simulations with a low quadrupole (as observed) indicate a bias of +0.31+/- 0.04. Derived values for 68% confidence intervals are given corrected (and not corrected) for our estimated biases. Including the quadrupole anisotropy, the most likely quadrupole-normalized amplitude is Q(sub rms-PS) = 14.3(sup + 5.2 sub -3.3) micro-K (12.8(sup + 5.2 sub -3.3) micro-K0 with a spectral index n = 1.42(sup + 0.49 sub -0.55)(n = 1.53(sup + 0.49 sub -0.55). With n fixed to 1.0 the most likely amplitude is 18.2 +/- 11.5 micro-K (17.4 +/- 1.5 micro-K). The marginal likelihood of n is 1.42 +/- 0.37 (1.53 +/- 0.37). Excluding the quadrupole anisotropy, the most likely quadrupole-normalized amplitude is Q(sub rms-PS) = 17.4(sup + 7.5 sub -5.2) micro-K (15.8(sup + 7.5 sub -5.2) micro-K) with a spectral index n = 1.11(sup + 0.60 sub -0.55) (n = 1.22(sup + 0.60 sub -0.55). With n fixed to 1.0 the most likely amplitude is 18.6 +/- 1.6 micro-K (18.2 +/- 1.6 micro-K). The marginal likelihood of n is 1.11 +/- 0.40 (1.22 +/- 0.40). Our best estimate of the dipole from the 2 yr DMR data is 3.363 +/- 0.024 mK toward Galactic coordinates (l, b) = (264.4 deg +/- 0.2 deg, 48.1 deg +/- 0.4 deg), and our best estimate of the rms quadrupole amplitude in our sky is 6 +/- 3 micro-K (68% CL).

Bennett, C. L.↗

NASA NTRS1994

The amplitude and spectral index of the large angular scale anisotropy in the cosmic microwave background radiation

In many cosmological models, the large angular scale anisotropy in the cosmic microwave background is parameterized by a spectral index, n, and a quadrupolar amplitude, Q. For a Harrison-Peebles-Zel'dovich spectrum, n = 1. Using data from the Far Infrared Survey (FIRS) and a new statistical measure, a contour plot of the likelihood for cosmological models for which -1 less than n less than 3 and 0 equal to or less than Q equal to or less than 50 micro K is obtained. Depending upon the details of the analysis, the maximum likelihood occurs at n between 0.8 and 1.4 and Q between 18 and 21 micro K. Regardless of Q, the likelihood is always less than half its maximum for n less than -0.4 and for n greater than 2.2, as it is for Q less than 8 micro K and Q greater than 44 micro K.

Ganga, Ken↗

NASA NTRS1994

Analysis of small-scale microwave background radiation anisotropy in the presence of foreground contamination

Many of the current round of experiments searching for anisotropies in the microwave background radiation (MBR) are confronting the problem of how to disentangle the cosmic signal from contamination due to Galactic and intergalactic foreground sources. Here we show how commonly used likelihood function techniques can be generalized to account for foreground. Specifically we set some restrictions on the spectrum of foreground contamination but allow the amplitude to vary arbitrarily. The likelihood function thus generalized gives reasonable limits on the MBR anisotropy which, in some cases, are not much less restrictive than what one would get from more detailed modeling of the foreground. Furthermore, the likelihood function is exactly the same as one would obtain by simply projecting out foreground contamination and looking at the reduced data set. We apply this generalized analysis to the recent medium-angle data sets of ACME-HEMT (Gaier et al. 1992; Schuster et al. 1993) and MAX (Meinhold et al. 1993; Gunderson et al. 1993). The resulting analysis constrains the one free parameter in the standard cold dark matter theory to be Q(sub rms-ps) = 18(sub -5 sup +8) microKelvin. This best fit value, although in striking agreement with the normalization from Cosmic Background Explorer (COBE), is not a very good fit, with an overall chi-squared/degrees of freedom = 208/168. We also argue against three commonly used methods of dealing with foreground: (1) ignoring it completely; (2) subtracting off a best-fit foreground and treating the residuals as if uncontaminated; and (3) culling data which appears to be contaminated by foreground.

Dodelson, Scott↗

NASA NTRS2000

A Recommended Procedure for Estimating the Cosmic Ray Spectral Parameter of a Simple Power Law

A simple power law model consisting of a single spectral index a(f(sub i)) is believed to be an adequate description of the galactic cosmic ray (GQ proton flux at energies below 1013 eV. Two procedures for estimating a(f(sub i)), referred as (1) the method of moments, and (2) maximum likelihood, are developed and their statistical performance compared. I concluded that the maximum likelihood procedure attains the most desirable statistical properties and is hence the recommended statistic estimation procedure for estimating a1. The maximum likelihood procedure is then generalized for application to a set of real cosmic ray data and thereby makes this approach applicable to existing cosmic ray data sets. Several other important results, such as the relationship between collecting power and detector energy resolution, as well as inclusion of a non-Gaussian detector response function, are presented. These results have many practical benefits in the design phase of a cosmic ray detector because they permit instrument developers to make important trade studies in design parameters as a function of one of the science objectives, which is particularly important for space-based detectors where physical parameters, such as dimension and weight, impose practical limits to the design envelope.

Howell, Leonard W.↗

NASA NTRS2001

Quantifying and Improving International Space Station Survivability Following Orbital Debris Penetration

The increase of the orbital debris environment in low-earth orbit has prompted NASA to develop analytical tools for quantifying and lowering the likelihood of crew loss following orbital debris penetration of the International Space Station (ISS). NASA uses the Manned Spacecraft and Crew Survivability (MSCSurv) computer program to simulate the events that may cause crew loss following orbital debris penetration of ISS manned modules, including: (1) critical cracking (explosive decompression) of the module; (2) critical external equipment penetration (such as hydrazine and high pressure tanks); (3) critical internal system penetration (guidance, control, and other vital components); (4) hazardous payload penetration (furnaces, pressure bottles, and toxic substances); (5) crew injury (from fragments, overpressure, light flash, and temperature rise); (6) hypoxia from loss of cabin pressure; and (7) thrust from module hole causing high angular velocity (occurring only when key Guidance, Navigation, and Control (GN&C) equipment is damaged) and, thus, preventing safe escape vehicle (EV) departure. MSCSurv is also capable of quantifying the 'end effects' of orbital debris penetration, such as the likelihood of crew escape, the probability of each module depressurizing, and late loss of station control. By quantifying these effects (and their associated uncertainties), NASA is able to improve the likelihood of crew survivability following orbital debris penetration due to improved crew operations and internal designs.

Williamsen, Joel↗

NASA NTRS2005

Risk Management for Human Support Technology Development

NASA requires continuous risk management for all programs and projects. The risk management process identifies risks, analyzes their impact, prioritizes them, develops and carries out plans to mitigate or accept them, tracks risks and mitigation plans, and communicates and documents risk information. Project risk management is driven by the project goal and is performed by the entire team. Risk management begins early in the formulation phase with initial risk identification and development of a risk management plan and continues throughout the project life cycle. This paper describes the risk management approach that is suggested for use in NASA's Human Support Technology Development. The first step in risk management is to identify the detailed technical and programmatic risks specific to a project. Each individual risk should be described in detail. The identified risks are summarized in a complete risk list. Risk analysis provides estimates of the likelihood and the qualitative impact of a risk. The likelihood and impact of the risk are used to define its priority location in the risk matrix. The approaches for responding to risk are either to mitigate it by eliminating or reducing the effect or likelihood of a risk, to accept it with a documented rationale and contingency plan, or to research or monitor the risk, The Human Support Technology Development program includes many projects with independently achievable goals. Each project must do independent risk management, considering all its risks together and trading them against performance, budget, and schedule. Since the program can succeed even if some projects fail, the program risk has a complex dependence on the individual project risks.

jones, Harry↗

NASA NTRS2008

The Integrated Medical Model: Statistical Forecasting of Risks to Crew Health and Mission Success

The Integrated Medical Model (IMM) helps capture and use organizational knowledge across the space medicine, training, operations, engineering, and research domains. The IMM uses this domain knowledge in the context of a mission and crew profile to forecast crew health and mission success risks. The IMM is most helpful in comparing the risk of two or more mission profiles, not as a tool for predicting absolute risk. The process of building the IMM adheres to Probability Risk Assessment (PRA) techniques described in NASA Procedural Requirement (NPR) 8705.5, and uses current evidence-based information to establish a defensible position for making decisions that help ensure crew health and mission success. The IMM quantitatively describes the following input parameters: 1) medical conditions and likelihood, 2) mission duration, 3) vehicle environment, 4) crew attributes (e.g. age, sex), 5) crew activities (e.g. EVA's, Lunar excursions), 6) diagnosis and treatment protocols (e.g. medical equipment, consumables pharmaceuticals), and 7) Crew Medical Officer (CMO) training effectiveness. It is worth reiterating that the IMM uses the data sets above as inputs. Many other risk management efforts stop at determining only likelihood. The IMM is unique in that it models not only likelihood, but risk mitigations, as well as subsequent clinical outcomes based on those mitigations. Once the mathematical relationships among the above parameters are established, the IMM uses a Monte Carlo simulation technique (a random sampling of the inputs as described by their statistical distribution) to determine the probable outcomes. Because the IMM is a stochastic model (i.e. the input parameters are represented by various statistical distributions depending on the data type), when the mission is simulated 10-50,000 times with a given set of medical capabilities (risk mitigations), a prediction of the most probable outcomes can be generated. For each mission, the IMM tracks which conditions occurred and decrements the pharmaceuticals and supplies required to diagnose and treat these medical conditions. If supplies are depleted, then the medical condition goes untreated, and crew and mission risk increase. The IMM currently models approximately 30 medical conditions. By the end of FY2008, the IMM will be modeling over 100 medical conditions, approximately 60 of which have been recorded to have occurred during short and long space missions.

Fitts, M. A.↗

NASA NTRS2012

Combining Ratio Estimation for Low Density Parity Check (LDPC) Coding

The Low Density Parity Check (LDPC) Code decoding algorithm make use of a scaled receive signal derived from maximizing the log-likelihood ratio of the received signal. The scaling factor (often called the combining ratio) in an AWGN channel is a ratio between signal amplitude and noise variance. Accurately estimating this ratio has shown as much as 0.6 dB decoding performance gain. This presentation briefly describes three methods for estimating the combining ratio: a Pilot-Guided estimation method, a Blind estimation method, and a Simulation-Based Look-Up table. The Pilot Guided Estimation method has shown that the maximum likelihood estimates of signal amplitude is the mean inner product of the received sequence and the known sequence, the attached synchronization marker (ASM) , and signal variance is the difference of the mean of the squared received sequence and the square of the signal amplitude. This method has the advantage of simplicity at the expense of latency since several frames worth of ASMs. The Blind estimation method s maximum likelihood estimator is the average of the product of the received signal with the hyperbolic tangent of the product combining ratio and the received signal. The root of this equation can be determined by an iterative binary search between 0 and 1 after normalizing the received sequence. This method has the benefit of requiring one frame of data to estimate the combining ratio which is good for faster changing channels compared to the previous method, however it is computationally expensive. The final method uses a look-up table based on prior simulated results to determine signal amplitude and noise variance. In this method the received mean signal strength is controlled to a constant soft decision value. The magnitude of the deviation is averaged over a predetermined number of samples. This value is referenced in a look up table to determine the combining ratio that prior simulation associated with the average magnitude of the deviation. This method is more complicated than the Pilot-Guided Method due to the gain control circuitry, but does not have the real-time computation complexity of the Blind Estimation method. Each of these methods can be used to provide an accurate estimation of the combining ratio, and the final selection of the estimation method depends on other design constraints.

Mahmoud, Saad↗

NASA NTRS2015

High Performance EVA Glove Collaboration: Glove Injury Data Mining Effort

Human hands play a significant role during Extravehicular Activity (EVA) missions and Neutral Buoyancy Lab (NBL) training events, as they are needed for translating and performing tasks in the weightless environment. Because of this high frequency usage, hand and arm related injuries are known to occur during EVA and EVA training in the NBL. The primary objectives of this investigation were to: 1) document all known EVA glove related injuries and circumstances of these incidents, 2) determine likely risk factors, and 3) recommend interventions where possible that could be implemented in the current and future glove designs. METHODS: The investigation focused on the discomforts and injuries of U.S. crewmembers who had worn the pressurized Extravehicular Mobility Unit (EMU) spacesuit and experienced 4000 Series or Phase VI glove related incidents during 1981 to 2010 for either EVA ground training or in-orbit flight. We conducted an observational retrospective case-control investigation using 1) a literature review of known injuries, 2) data mining of crew injury, glove sizing, and hand anthropometry databases, 3) descriptive statistical analyses, and finally 4) statistical risk correlation and predictor analyses to better understand injury prevalence and potential causation. Specific predictor statistical analyses included use of principal component analyses (PCA), multiple logistic regression, and survival analyses (Cox proportional hazards regression). Results of these analyses were computed risk variables in the forms of odds ratios (likelihood of an injury occurring given the magnitude of a risk variable) and hazard ratios (likelihood of time to injury occurrence). Due to the exploratory nature of this investigation, we selected predictor variables significant at p≤0.15. RESULTS: Through 2010, there have been a total of 330 NASA crewmembers, from which 96 crewmembers performed 322 EVAs during 1981-2010, resulting in 50 crewmembers being injured inflight and 44 injured during 11,704 ground EVA training events. Of the 196 glove related injury incidents, 106 related to EVA and 90 to EVA training. Over these 196 incidents, 277 total injuries (126 flight; 151 training) were reported and were then grouped into 23 types of injuries. Of EVA flight injuries, 65% were commonly reported to the hand (in general), metacarpophalangeal (MCP) joint, and finger (not including thumb) with fatigue, abrasion, and paresthesia being the most common injury types (44% of total flight injuries). Training injuries totaled to more than 70% being distributed to the fingernail, MCP joint, and finger crotch with 88% of the specific injuries listed as pain, erythema, and onycholysis. Of these training injuries, when reporting pain or erythema, the most common location was the index finger, but when reporting onycholysis, it was the middle finger. Predictor variables specific to increased risk of onycholysis included: female sex (OR=2.622), older age (OR=1.065), increased duration in hours of the flight or training event (OR=1.570), middle finger length differences in inches between the finger and the EVA glove (OR=7.709), and use of the Phase VI glove (OR=8.535). Differentiation between training and flight and injury reporting during 2002-2004 were significant control variables. For likelihood of time to first onycholysis injury, there was a 24% reduction in rate of reporting for each year increase in age. Also, more experienced crewmembers, based on number of EVA flight or training events completed, were less likely to report an onycholysis injury (3% less for every event). Longer duration events also found reporting rates to occur 2.37 times faster for every hour of length. Crewmembers with larger hand size reported onycholysis 23% faster than those with smaller hand size. Finally, for every 1/10th of an inch increase in difference between the middle finger length and the glove, the rate of reporting increased by 60%. DISCUSSION: One key finding was that the Series 4000 glove had a lower injury risk than the Phase VI, which provides a platform for further evaluation. General interventions that reduce hand overexertion and repetitive use exposure through tool development, procedural changes and shorter exposures may be one mitigation path, but due to the way the training event times were reported, we cannot provide a guideline for a specific event duration change. When the finger length was different from the glove length, the risk of injury increased indicating that the use of larger finger take-ups could be contributing to injury and therefore may not be recommended. Prior to this investigation, there was one previous investigation indicating hand anthropometry may be related to onycholysis. We found different hand anthropometry variables indicated by this investigation as compared to the prior, specifically differences in middle finger length compared to glove finger length, which point more towards a sizing issue than a specific anthropometry issue. Additionally, although this investigation has identified sizing as an issue, the force and environmental-related variables of the EVA glove that could also cause injury were not accounted for.

Reid, C. R.↗

NASA NTRS2015

New York City Panel on Climate Change 2015 Report: Climate Observations and Projections - Chapter 1

During 2013 and 2014, numerous international (IPCC, 2013) and national (Melillo et al., 2014; Gordon, 2014) reports have concluded that human activities are changing the climate, leading to increased vulnerability and risk. Since the industrial revolution, fossil fuel burning, industrial activity, and land use changes have led to a 40% increase in heat-trapping carbon dioxide (CO2), and an approximately 150% increase in methane (CH4), another powerful greenhouse gas (GHG), has been observed. Global temperatures have increased by close to 1 C since 1880 as the upper oceans have warmed and polar ice has retreated. These and other climate changes are projected to accelerate as greenhouse gas concentrations continue to rise. In the coming decades, climate change is extremely likely to bring warmer temperatures in the New York metropolitan region (see Box. 1.1 and Fig.1.1 for key definitions and terms). Heat waves are very likely to increase; total annual precipitation will likely increase and brief, intense rainstorms are very likely to increase. Because of incomplete knowledge about exactly how much climate change will occur, choosing among policies for reducing future damages requires prudent risk management (Yohe and Leichenko, 2010; Kunreuther et al., 2013). Given differing risk tolerances among stakeholders, a risk management approach allows for a range of possible climate change outcomes to be examined with associated uncertainties surrounding their likelihoods. The New York City Panel on Climate Change 2 (NPCC2) projections can be used to inform planning across multiple governmental scales (e.g., city, county, state) in the New York metropolitan region. Such coordinated efforts can serve as test cases for successful local, state, and federal coordination for integrated climate adaptation initiatives. This chapter describes the global climate system, and presents observed temperature and precipitation trends and projections for the region. Chapter 2 (NPCC, 2015) focuses on sea level rise and possible changes in coastal storms. Chapter 3 and Chapter 4 (NPCC, 2015) describe efforts to better understand the region's vulnerability to coastal flooding during coastal storms. The treatment of likelihood related to the NPCC projections is similar to that developed by the Intergovernmental Panel on Climate Change Fourth and Fifth Assessment Reports (IPCC, 2007; 2013), with six likelihood categories (Box 1.1 and Fig. 1.1). The assignment of climate hazards to these categories is based on observed data, global climate model simulations, published literature, and expert judgment.

climate change↗

NASA NTRS2016

SC-228 Inclusion of DAA Warning Alert for TCAS Interoperability

This white paper summarizes NASA research results that have informed Special Committee 228 (SC-228) discussions and decisions regarding the inclusion of a warning-level alert within the detect and avoid (DAA) alerting structure for unmanned aircraft systems (UAS). For UAS, the removal of the pilot from onboard the aircraft has eliminated the ability of the ground-based pilot in command (PIC) to use out-the-window visual information to make judgments about a potential threat of a loss of well clear with another aircraft. As a result, the DAA traffic display will be the primary source of information that the PIC can use to execute the three primary well clear functions: 1) detect a potential loss of well clear, 2) determine a resolution maneuver, and 3) upload that maneuver to the aircraft via the ground control station (GCS). In addition, pilots are required to coordinate with air traffic control (ATC) prior to maneuvering off of their approved flight plan. In determining an appropriate resolution maneuver to avoid a loss of well clear, the PIC must decide both when and how to maneuver, and both the timeliness and the accuracy (i.e., correctness) of the maneuver are critical to reducing the likelihood and/or severity of a loss of well clear. Alerting information is one of three critical components of the DAA display, along with traffic information elements (e.g., relative heading, speed and altitude) and maneuver guidance. Alerting information and maneuver guidance, in particular, have been found to have a significant impact, both statistically and practically, on pilots' ability to avoid and minimize the severity of losses of well clear While all three display components are key to pilots performing the traffic avoidance task of remaining well clear, in general, alerting information provides crucial information about when a resolution maneuver is required while maneuver guidance assists the pilot in determining how best to maneuver. A fundamental task of the DAA alerting system is to provide critical timing information to the pilot about the potential for a loss of well clear with another aircraft. This is done by employing both temporal and spatial thresholds that indicate to the pilot the likelihood and imminence of a loss of well clear. The design of the DAA alerting thresholds is a balancing act between eliciting the desired pilot response in real loss of well clear threat events and reducing excessive, unnecessary, and/or uncoordinated UAS maneuvering within the air traffic environment; larger thresholds, both spatially and temporally, may increase the likelihood of a pilot avoiding a loss of well clear, but it can also increase the frequency of maneuvering - especially in cases where a maneuver is not actually needed to maintain well clear. A series of human in the loop (HITL) simulations have been conducted as part of NASA's Unmanned Aircraft Systems (UAS) Integration in the National Airspace System (NAS) project. The purpose of these HITLs has been to provide empirical results in order to inform development of the minimum human-machine interface requirements for the DAA system. This white paper will present those results which provide evidence of a human performance benefit (in terms of response times and ability to remain well clear of other aircraft) of the DAA warning alert both with and without a collision avoidance system on board the aircraft.

TCAS interoperability↗

NASA NTRS2017

Consideration of Collision "Consequence" in Satellite Conjunction Assessment and Risk Analysis

Classic risk management theory requires the assessment of both likelihood and consequence of deleterious events. Satellite conjunction risk assessment has produced a highly-developed theory for assessing collision likelihood but holds a completely static solution for collision consequence, treating all potential collisions as essentially equally worrisome. This may be true for the survival of the protected asset, but the amount of debris produced by the potential collision, and therefore the degree to which the orbital corridor may be compromised, can vary greatly among satellite conjunctions. This study leverages present work on satellite collision modeling to develop a method by which it can be estimated, to a particular confidence level, whether a particular collision is likely to produce a relatively large or relatively small amount of resultant debris and how this datum might alter conjunction remediation decisions. The more general question of orbital corridor protection is also addressed, and a preliminary framework presented by which both collision likelihood and consequence can be jointly considered in the risk assessment process.

Hejduk, M.↗

NASA NTRSDate not supplied

Improving Efficacy and Safety of Pharmacological Treatment Through Precision Medicine and Pharmacogenomics for Human Deep Space Exploration

INTRODUCTION: Future spaceflight will require increased crew medical autonomy as exploration class missions expanding duration and distance from Earth, especially for Mars missions. As mission duration increases, it will be even more essential to have appropriate amounts of effective medication to ensure the maintenance of crew health and performance. Conversely, mass and volume constraints will become more severe as future spaceflight expands beyond low Earth orbit, where resupply is difficult or becomes impossible. These constraints thus convey an urgency to further tailor medications included in the spacecraft formulary and increased examination of appropriate dosing regimens. BACKGROUND: Precision Health is an exciting area of cutting-edge research and medicine focused on maintaining an individual’s health and performance through in-depth understanding of an individual’s unique factors and molecular profiles. This approach can be adapted to better predict, monitor, and address physiological responses to the spaceflight environment. One example is the field of pharmacogenomics (PGX),the study of how the expressed genome impacts drug responses with the goal of prescribing the right dose of the right drug at the right time. Specifically, PGX testing provides valuable information on an individual’s precise allelic variations to guide physicians in making informed decisions on pharmaceutical choice and dosing to avoid adverse drug events and maximize pharmacological efficacy. The goal of this study was to evaluate which drugs in the current space pharmacy could be evaluated using PGX testing and to understand the potential impact on the health and wellness of the astronaut population. Additionally, we sought to evaluate clinically available FDA-approved PGX testing solutions to better understand its applicability. METHODS: A complete list of drugs onboard the International Space Station (ISS) was analyzed for risk and likelihood of drug failure and PGX actionability. This analysis encompassed both personal astronaut medications, including supplements and over the counter drugs (n=151) and ISS MedKit formulary medications (n=95). Duplicate medications and different formulations were removed, which resulted in 157 total drugs used in the subsequent analysis. A 5x5 risk assessment table was produced by examining the likelihood of drug failure compared to the consequence of drug failure. Likelihood of individual drug failure was defined by whether existing processes are sufficient to prevent adverse events, as ranked from 1 (very low, can easily be prevented) to 5 (very high, cannot be prevented) during a Mars mission. In contrast, the consequence of drug failure was defined by impact to safety, schedule, cost or technical and ranked from 1 (very low) to 5 (very high).A comprehensive assessment of commercially available PGX solutions is currently underway to evaluate specimen requirements, cost/benefit analysis (cost vs. number of alleles assessed), utility of variant analysis, relevance to inflight medication usage, quality of reporting in enabling clinical application, and ease of integration into electronic medical records. RESULTS: Risk assessments(LxC 5x5 table) indicated29medicationswere in the yellow or red zone driven predominantly by drug failure or safety concerns, with the remainder(n=128)of the medications in the green zone where risk is acceptable. We found that current PGX testing results could impact 21% of the total medications in the ISS MedKit and IMAK; of these, 9 medications currently have direct clinically actionable guidance available. Results of the clinical PGX solution evaluations as related to these medications will be presented. CONCLUSION: PGX testing has demonstrated clear benefits in terrestrial medicine and clinical environments for the selection of proper medications, avoiding adverse drug reactions, and maximizing drug efficacy. We propose that similar benefits would be bestowed on the astronaut and commercial spaceflight passenger population by performing preemptive pre-flight PGX testing to reduce risk of mission failure due to ineffective or toxic medications, improve targeting drug efficacy and safety, and further open the door to countermeasure research exploring PGX-related allelic variants. For example, PGX results could allow tailoring of specific medications at optimal doses more precisely to each individual astronaut, particularly in areas of space motion sickness, sleep aids, and analgesics. An additional benefit is that PGX results could provide information for better planning of the components of a space pharmacy for deep space missions to be more cost effective and more efficient in the utilization of limited pharmaceutical resources. Finally, while PGX testing of the astronaut corps is not currently conducted, this approach could provide immediate impact in support of mission success by reducing risks, optimizing astronaut performance, and providing valuable insights into long-term astronaut health. Such advancements in clinical decision making are important next steps in building dynamic individual risk profiles for astronauts, increasing crew autonomy and providing tailored countermeasures

Alice R W Tang↗

NASA NTRSDate not supplied

Improving Efficacy and Safety of Pharmacological Treatment Through Precision Health and Pharmacogenomics

INTRODUCTION: Future spaceflight will require increased crew medical autonomy as exploration class missions expand in duration and distance from Earth, especially for Mars missions. As mission duration increases, it will be essential to have appropriate amounts of effective medication to ensure the maintenance of crew health and performance. Conversely, mass and volume constraints will become more severe as future spaceflight expands beyond low Earth orbit, where resupply is difficult or becomes impossible. These constraints thus convey an urgency to tailor medications for individual crewmembers and further examine appropriate dosing regimens. BACKGROUND: Precision Health is an exciting area of medicine focused on maintaining an individual’s health and performance through in-depth understanding of an individual’s unique clinical and environmental history, genetic makeup, and molecular profiles. This approach can be adapted to better predict, monitor, and address physiological responses to the spaceflight environment. A subset of this field is pharmacogenomics (PGX), the study of how the expressed genome impacts drug responses with the goal of prescribing the right dose of the right drug at the right time. Specifically, PGX testing provides valuable information on an individual’s precise allelic variations to guide physicians in making informed decisions on drug choice and dosing to avoid adverse events and maximize efficacy. The study goal was to identify which current space pharmacy drugs could be evaluated using PGX testing and to understand the potential impact on the health and wellness of the astronaut population. Additionally, we sought to evaluate clinically available FDA-approved PGX testing solutions to better understand its applicability. METHODS: A complete list of drugs on the ISS was analyzed for risk and likelihood of drug failure and PGX actionability. This analysis encompassed both astronauts’ personal medications, including supplements and over the counter drugs (n=151) contained in the ISS medical accessory kit (IMAK), and ISS MedKit formulary medications (n=95). Duplicate medications and different formulations were removed, which resulted in a total of 157 drugs used in the subsequent analysis. A 5x5 risk assessment table was produced by examining the likelihood of drug failure compared to the consequence of drug failure (LxC). Likelihood of individual drug failure was defined by whether existing processes are sufficient to prevent ineffective treatment or impactful side effect events, as ranked from 1 (very low, can easily be prevented) to 5 (very high, cannot be prevented) during a Mars mission. In contrast, the consequence of drug failure was defined by impact to safety, schedule, cost, or technical criteria and ranked from 1 (very low) to 5 (very high). An assessment of PGX reference laboratories is currently underway to evaluate sample requirements, benefit analysis (cost vs. utility of allele variant analysis), relevance to inflight medication usage, quality of reporting in enabling clinical application, and ease of integration into electronic medical records. RESULTS: Risk assessments (LxC 5x5 table) indicated 128 medications were in the green zone where risk is acceptable, with the remaining 29 of the medications in the yellow or red zone driven predominantly due to drug failure or safety concerns. We found that current PGX testing results could impact 21% of the total medications in the ISS MedKit and IMAK; of these, 9 medications currently have direct clinically actionable guidance available. Results of the clinical PGX solution evaluations as related to these medications will be presented. CONCLUSION: PGX testing has demonstrated clear benefits in terrestrial medicine and clinical environments for the selection of proper medications, avoiding adverse drug reactions, and maximizing drug efficacy. We propose that similar benefits would be bestowed on the astronaut and commercial spaceflight passenger population by performing preemptive preflight PGX testing to reduce risk of mission failure due to ineffective or toxic medications, improve drug efficacy, and further open the door to countermeasure research. For example, PGX results could allow tailoring of specific medications at optimal doses more precisely to each individual astronaut, particularly in areas of space motion sickness, sleep aids, and analgesics. An additional benefit is that PGX results could provide information for better planning of the components of a space pharmacy for deep space missions to be more effective and efficient in the utilization of limited pharmaceutical resources. Finally, while PGX testing of the astronaut corps is not currently conducted, this approach could provide immediate impact in support of mission success by reducing risks, optimizing astronaut performance, and providing valuable insights into long-term astronaut health. Such advancements in clinical decision making are important next steps in building dynamic individual risk profiles for astronauts, increasing selection of the best treatment choice, and providing tailored countermeasures for individual crewmembers.

Pharmacogenomics↗

NASA NTRS2022

Constraining Warm Dark Matter and Population III Stars with the Global 21 cm Signal

Upcoming ground- and space-based experiments may have sufficient accuracy to place significant constraints upon high-redshift star formation, Reionization, and dark matter (DM) using the global 21 cm signal of the intergalactic medium. In the early universe, when the relative abundance of low-mass DM halos was important, measuring the global signal would place constraints on the damping of structure formation caused by DM having a higher relic velocity (warm dark matter, or WDM) than in cold dark matter. Such damping, however, can be mimicked by altering the star formation efficiency (SFE) and can be difficult to detect because of the presence of Population III stars with unknown properties. We study these various cases and their degeneracies with the WDM mass parameter mX using a Fisher matrix analysis. We study the mX = 7 keV case and a star formation model that parameterizes the SFE as a strong function of halo mass and include several variations of this model along with three different input noise levels for the likelihood; we also use a minimum halo virial temperature for collapse near the molecular cooling threshold. We find that when the likelihood includes only Population II stars, mX is constrained to an uncertainty of ∼0.4 keV for all models and noise levels at the 68% confidence level. When the likelihood includes weak Population III stars, mX ∼ 0.3 keV, and if Population III star formation is relatively efficient, mX ∼ 0.1 keV uncertainty, with tight Population III star formation parameter constraints. Our results show that the global 21 cm signal is a promising test-bed for WDM models, even in the presence of strong degeneracies with astrophysical parameters.

Cosmology↗

NASA NTRS2022

Planetary protection assessment of radioisotope thermoelectric generator (RTG)-powered landed missions to ocean worlds: application to Enceladus

Landed missions to icy worlds with a subsurface liquid water ocean must meet planetary protection requirements, and ensure a sufficiently small likelihood of any microorganism-bearing part of the landed element reaching the ocean. A higher bound on this likelihood is set by the potential for radioisotope thermoelectric generator (RTG) power sources, the hottest possible landed element, to melt through the ice shell and reach the ocean. Here, we quantify this potential as a function of three key parameters: surface temperature, ice shell thickness (i.e., heat flux through the shell), and thickness of a porous (insulating) snow or regolith cover. Although the model we describe can be applied to any ocean world, we present results in the context of a landed mission concept to the south polar terrain of Saturn’s moon Enceladus. In this particular context, we discuss planetary protection considerations for landing site selection. The likelihood of forward microbial contamination of Enceladus’ ocean by an RTG-powered landed mission can be made sufficiently low to not undermine compliance with planetary protection policy.

Marc Neveu↗

NASA NTRSDate not supplied

Selection of Next Priority IMPACT Medical Conditions Based on Available Terrestrial and Spaceflight Data

BACKGROUND: As the era of exploration class missions begins, identification of medical conditions that may occur and require management becomes essential for the modeling of medical risk. To this end, NASA has developed IMPACT (Informing Mission Planning via Analysis of Complex Tradespaces), a suite of tools to assist in assessment of medical risk analysis. It has incorporated an initial list of the 120 conditions of highest concern, labeled the IMPACT condition list 1.0 (ICL 1.0). This abstract describes a method for prioritizing the 92 conditions included on the Proposed Future Conditions List (PFCL) for inclusion in future iterations of the ICL. OVERVIEW: To construct the Prioritized Proposed Future Conditions List (P-PFCL), each condition on the PFCL was scored as “low,” “medium,” or “high” on each of four variables: incidence, likelihood of significant task impairment, diagnostic and treatment complexity, and treatment futility. Qualitative assessment using clinical judgement was utilized to score complexity, futility, and likelihood of impairment. Incidence was assessed quantitatively using spaceflight data and/or analog populations where available then assigned a score using established cutoffs. Logarithmic numerical values were assigned to each category label. A Prioritization Score was generated for each condition by taking the product of incidence and likelihood of task impairment (risk) divided by the product of complexity and futility (difficulty of care), with higher values corresponding to higher priority for future inclusion in the ICL. DISCUSSION: The described methods allow for the generation of a ranked P-PFCL to act as a decision support tool for selection of the next generation of modeled medical conditions. Some of the conditions ranked highly on the P-PFCL include EVA-related upper and lower extremity sprain/strain, iron deficiency, delirium, and hypertension, among others. While this effort does not attempt to quantify the absolute risk associated with each condition, it does attempt to semi-quantitatively estimate the risk of each condition relative to the other possible conditions. This tool in concert with subject matter expert opinion could optimize the future use of limited resources thereby producing a more accurate medical risk model, which will be essential to the upcoming exploration class missions.

Michael Pohlen↗

NASA NTRS2023

IMPACTing Medical System Design with a Risk Analysis Tool [“IMPACT” sur la Conception du Système Médical avec un Outil d'Analyse des Risques]

Background: Following the success of Artemis I, NASA is preparing for human extended duration missions. Ongoing efforts are focused on mitigating mission-related risks, including those affecting crew health and performance. Communication latency, logistics of resupply and time frame of medical evacuation are barriers to provision of healthcare for these missions, especially with respect to constraints in mass, volume, and crew training. An in-depth assessment of medical risks, capabilities and resources for a specific mission design is necessary to determine an optimal balance that maximizes likelihood of mission success. Overview: IMPACT (Informed Mission Planning via Analysis of Complex Tradespaces) is a dynamic tool designed to estimate medical risk and outcomes for a specific mission design. In its current iteration, a list of medical conditions selected based on likelihood of occurrence and/or consequence was linked to a set of clinical capabilities and resources necessary for diagnosis and management. A probabilistic risk analysis tool was then used to identify and estimate the likelihood and consequence of risks through the following outcome metrics: loss of crew life (inflight mortality due to medical conditions), need for medical evacuation (return to definitive care), and crew disability (task time affected based on how medical conditions influence the ability to perform specific exploration mission crew tasks). Finally, the model’s optimization algorithm provides recommendations for medical capabilities that maximize risk mitigation relative to mass and volume constraints. In the Spring of 2023, IMPACT was utilized to estimate outcome metrics for a design reference mission that would be representative of an extended duration Artemis mission. Notional data generated were then used to determine a recommended set of medical capabilities and resources relative to user-defined mass and volume constraints. A multidisciplinary team has also been updating IMPACT to strengthen the model’s fidelity. Figure 1 shows how updates to outcome metric inputs for the conditions resulted in different capability and resource allocation recommendations. Discussion: This presentation will discuss the IMPACT tool and share the latest data generated for a representative extended duration Artemis mission. Efforts to improve the fidelity of data generated by the model’s algorithm will also be discussed.

K A Shair↗