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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.

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At least 505 records · Page 28

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NASA NTRS2018

Low-Latency Teleoperations: Operational Implications for Human Space Exploration

Low-latency teleoperations (LLT) is envisioned to be an element of human exploration missions in a number of different applications. LLT can be broadly considered to encompass any remote operation of an asset with a communication delay that is less than the human response time to allow for what is effectively "real-time" or "near real-time" operations. This paper will explore motivations and operational implications for why and how LLT might be used for human exploration space missions. LLT analyses have been performed under the auspices of the NASA Human Spaceflight Architecture Team (HAT) and Evolvable Mars Campaign (EMC). The EMC created a flexible, evolvable, capability-driven architectural strategy to enable a sustainable long-term human presence at Mars. LLT is envisioned to be part of that strategy for both in-space and on-surface applications, and this paper will expand on operational considerations within that broader strategic context, as well additional contexts. Some operational implications explored in this paper, derived largely from previous work, are: (1) crew mission support, for which we will address roles for Mission Control on earth, balanced with the capability for crew and robotic assets to operate independently, (2) science operations, with a focus on "backroom" support, highly dynamic science, and enhanced science return and efficiency, and (3) operational efficiency at a deep-space destination such as Mars, including implications for communications infrastructures and how to leverage and balance system autonomy with crew operations, both of which can inform the overall operational "choreography" between crew members, multiple shifts, and exploration assets.

human spaceflight↗

NASA NTRS2018

Automated Scenario Generation for Human-in-the-Loop Simulations

Automated Multi-Aircraft Control System scenario generation for Human-in-the-Loop evaluations of air traffic management concepts is described. Methods for analyzing and comparing the seed-scenario generated using the automated process and the Human-in-the-Loop-scenario designed to meet the experiment objectives are discussed. The main findings are: (1) many of the characteristics of the seed-scenario used for constructing the Human-in-the-Loop-scenario are preserved in the Human-in-the-Loop Scenario, (2) landing characteristics of the traffic generated by the Multi-Aircraft Control System using the input scenario compare reasonably well with that intended in the input scenario, and (3) many of desired characteristics of the Human-in-the-Loop-scenario can be achieved by further automation.

SMART-NAS Testbed↗

NASA NTRS2018

Human Automation Teaming: Lessons Learned and Future Directions

Full autonomy seems to be the goal for system developers in almost every area of the economy. However, as we move from automated systems to autonomous systems, designers have needed to insert humans to oversee automation that has traditionally been brittle or incomplete. This creates its own problems as the operator is usually out of the loop when the automation hands over problems that it cannot handle. To better handle these situations, it has been proposed that we develop human automation teams that have shared goals and objectives to support task performance. This paper will describe an initial model of Human Automation Teaming (HAT) which has three elements: transparency, bi-directional communications, and human-directed execution. Transparency in our model is a method for giving insight into the reasoning behind automated recommendations and actions, bi-directional communication allows the operator to communicate directly with the automation, and finally the automation defers execution to the human. The model was implemented through a number of features on an electronic flight bag (EFB) which are described in the paper. The EFB was installed in a mid-fidelity flight simulator and used by 12 airline pilots to support diversion decisions during off-nominal flight scenarios. Pilots reported that working with the HAT automation made diversion decisions easier and reduced their workload. They also reported that the information provided about diversion airports was similar to what they would receive from ground dispatch, thus making coordination with dispatch easier and less time consuming. These HAT features engender more trust in the automation when appropriate, and less when not, allowing improved supervision of automated functions by flight crews.

Human-Autonomy Teaming↗

NASA NTRS2017

Concepts for the Design of Human-Autonomy Systems

Over the last two years a number of workshops or similar meetings have been held under the auspice of NASA Ames Research Center that, although dealing with different primary foci, considered at some level the cross-cutting topic of humans-autonomous systems and the partnership between them. This publication presents findings from the reports of these meetings as they inform the process of designing autonomous systems to work in conjunction with humans. Some workshops were highly relevant to this question, others less so. Drawing from conclusions in these reports, this publication presents, at a high level, a summary of issues that could usefully be considered in the design process of automated systems working with human agents. Although differing in emphases, reports from the several workshops reflect many similar beliefs regarding human-autonomy teaming (HAT). Conclusions can be viewed as generally applicable to various aviation venues—air, ground, and air-ground interactions. The objective of the workshops was primarily to identify issues, concerns, and research needs associated with evolving human-autonomy systems—not in providing solutions. The analysis herewithin is generally limited to the findings in the workshop reports. And, since there was often commonality in findings among the several reports, no attempt is made to ascribe particular findings or observations to particular reports.

autonomy↗

NASA NTRS2015

Integrating Human Performance Measures into Space Operations: Beyond Our Scheduling Capabilities?

Current planning and scheduling software tools for International Space Station (ISS) support different flight controller teams as they plan daily space operations. Planning and scheduling tools capabilities include integrating digitized ISS state inputs, evaluating their expected future states, and propagating them over time. Extensive, custom-made computational models of operations, of objectives, and of operational constraints help ISS flight controllers identify where scheduled events violate constraints. Based on the current capabilities of these tools, this paper proposes how human performance measures could be better integrated into planning and scheduling tools for space mission operations. Future integration of human performance measures could be applied to state inputs (in this case, the astronaut’s state) and to modeling human performance operational constraints & operational objectives (i.e., assigned activities) with parameters that are relevant to human performance measures. Gaps between the state-of-the-art for human performance modeling and planning tools for future exploration missions are identified.

space operations↗

NASA NTRS2019

Exploring Human Factors Issues for Urban Air Mobility Operations

Urban air mobility (UAM) is currently receiving increased attention in the aviation literature as a new entrant into the airspace. Although the introduction of UAM offers the potential for significant benefits, it also creates the potential for fundamental change to the current air traffic management system. Several concepts are being explored to enable the development of a safe and efficient UAM system for near, mid and far term operations. A concept of operations for near term operations proposes several assumptions. Concepts for roles and responsibilities of human operators such as air traffic controllers propose different degrees of involvement. Identifying and exploring human factors issues is therefore a critical next step in the forward progression of concept development. A human-in-the-loop air traffic control simulation was used to investigate the effect of UAM traffic density and changes in current airspace routes and communication procedures on subjective controller workload and efficiency-related task performance. Findings indicate that although subjective workload was manageable for low density operations, medium and high density operations led to unmanageable levels of workload, leading to refusals to allow more vehicles into controlled airspace. By implementing a letter of agreement, verbal communications were reduced which were associated with reduced workload. Optimized routes were also associated with reduced workload and increased performance efficiency. Although these adjustments can positively support controller performance, workload still remained high during the high density UAM traffic scenarios. It is therefore suggested that, in order for UAM operation to become scalable, human operators will be required to work differently compared to current air traffic controllers. Future research should focus on the level and type of human operator or controller involvement and mated systems, to ensure safety and efficiency within UAM operations.

Air Traffic Management↗

NASA NTRSDate not supplied

Genomic and Phenotypic Associations to Predict Human Sensitivity to SpaceRadiation

High-linear energy transfer (LET) ionizing radiation is a major health hazard for astronauts who will be exposed to galactic cosmic rays during upcoming lunar and Mars missions. Predicting and mitigating this risk requires understanding the factors underlying individual radiation sensitivity. We started to address this challenge by identifying the genomic and phenotypic associations with sensitivity to low and high-LET ionizing radiation ex vivo in over 750 healthy human donors. We exposed primary human blood mononuclear cells to simulated galactic cosmic ray components: 350MeV/n 28Si, 350MeV/n 40Ar and 600MeV/n 56Fe particles, at 1.1 and 3 particles/100 sq.m fluences, as well as 0.1 Gy and 1 Gy doses of gamma rays, and analyzed the outcomes at 4 and 24 hours post-irradiation. We quantified DNA damage and repair responses based on 53BP1+ radiation-induced foci formation, together with oxidative stress and changes in secreted factors including immune cytokines and exosomes. We also analyzed phenotypic associations with spontaneous DNA repair foci at baseline prior to irradiation. We identified an increase in spontaneous DNA repair associated with age and latent viral infection, and observed that human spontaneous DNA repair foci at baseline can serve as a negative predictor of DNA repair and immunoregulatory cytokine production after irradiation. Furthermore, we observed a wide variability of subject- and LET-dependent radiation responses, with radiation-induced DNA repair foci increasing by dose and LET, and high-LET particle radiation resulting in more residual DNA damage compared to low-LET particles and gamma rays. We have developed multiple metrics to quantify human radio sensitivity across the spectrum of conditions. Here we present their dependence on radiation quality and phenotypic variables, including an age-dependent decrease in DNA repair after irradiation, and genomic associations with radio sensitivity based on low-coverage whole genome sequencing. We anticipate that our work will pave the way for understanding the spectrum of human radio sensitivity and identifying targets for countermeasure development to reduce DNA and cellular damage and radiation carcinogenesis during deep space exploration.

GWAS radiation human↗

NASA NTRS2022

Enabling Innovative Research on the International Space Station to Solve the Challenges of A Human Mission to Mars: Results of the ISS4Mars International Workshops 2020–2021

During the ISS4Mars workshops in 2020–2021, personnel from the International Space Station (ISS) partner agencies convened to reflect on scenarios for how the ISS could be used and its operations possibly modified to simulate aspects of a human mission to Mars. Scientific leaders, operations experts, crewmembers, managers, and flight surgeons discussed the five hazards of human spaceflight—gravity transitions, radiation, isolation and confinement, distance from Earth, and hostile closed environments—and considered how an ISS-based analog of Mars transit could benefit assessments and mitigations of these hazards. A focused writing team then discussed the advantages and disadvantages of each approach identified by the workshop participants before developing a set of eight use cases to consider the feasibility of implementing on the ISS. The writing team also identified the prerequisites needed, including ground analog studies simulating a mission to Mars required to verify measurements and procedures, before testing could begin on the ISS. Five of the use cases were considered feasible to assess in simulations using an ISS-based analog of Mars transit if some ground rules and assumptions were met. These five use cases were Earth-independent medical operations, Earth-independent integrated operations, life support and food for a one year duration, lower-body negative pressure as a countermeasure against the effects of exposure to microgravity, and fitness levels after landing. In addition, three more extensive interventions—extended Mars surface operations, a small-volume transit analog, and artificial gravity—were deemed unfeasible for testing on the ISS. Experience gained from the five use cases executed on the ISS may help answer some of the questions in the deferred scenarios, or it may be possible to complete them on another platform (e.g. commercial space station, lunar habitat). Simulating conditions during a Mars mission on the ISS will afford higher fidelity for assessing multiple integrated hazards of human spaceflight, however, ground analogs of Mars missions can be used to ensure effective measures and experimental design before testing begins on the ISS. The strategic concepts refined as part of these workshops were brought to a multilateral forum, Mulitlateral Human Research Planel for Exploration (MHRPE), where ISS partner agencies are now discussing implementation plans to provide new opportunities to use the ISS to prepare for deep space exploration over the coming decade. In this publication we present a summary of the international strategic plans for future research that will enable operations, software, and countermeasures to be developed that will reduce the risk to humans during future crewed missions to Mars.

Human space exploration↗

NASA NTRS2023

Computer Human Interface Challenges in Space Exploration

NASA’s plans to return humans to the Lunar surface require overcoming a variety of challenging technical and operational obstacles. In 2022, NASA formed the Extravehicular Activity (EVA) and Human Surface Mobility (HSM) Program (EHP) at the Johnson Space Center with responsibilities including development of space suits and surface mobility systems for Lunar missions. This program includes a Technology Development and Partnerships office chartered to identify high priority gaps in capabilities for Lunar surface mobility and to coordinate resources to close those gaps. This presentation details the EHP technology roadmap for “Informatics and Decision Support,” a subset of spacecraft avionics focused on effective and autonomous crew interaction with spaceflight systems. The gaps, grouped into displays, audio systems, and information technology infrastructure, are largely driven by the unique interaction requirements for human spacecraft and the severe radiation environments beyond low earth orbit. The roadmap identifies ongoing activities and paths to technology infusion into Lunar spacecraft. NASA is seeking input on the content and ideas for alternative paths to gap closure. Closing these gaps is important to successful human operations on the Lunar surface and vital to NASA’s long-term goal of human missions to Mars.

Spacecraft Displays↗

NASA NTRSDate not supplied

The Adaptable and Resilient Safety System: The Human Factor in Future In-Time Aviation Safety Management Systems

In-time integrated safety management will be paramount for safely enabling the envisioned transformations of the future National Airspace System (NAS). The path for realizing the vision includes addressing the increasing need for advanced data analytics and fusion of aviation safety data, managed by human decision-makers. The paper describes safety management systems and its’ challenges, and how the concept of In-time Aviation Safety Management Systems addresses the need to ensure an adaptable and resilient future safety system in the envisioned transformed NAS. Finally, it discusses potential human factors challenges, including new human roles and responsibilities, new information and cognitive requirements, new intelligent technologies that change human-system interaction and coordination, and new design paradigms for human system integration and teaming.

Aviation Safety↗

DOE OSTI2024

Human Factors Challenges in Modernizing Nuclear Power Plant Control Rooms

Jeffrey Joe has been invited to give a presentation entitled, “Human Factors Challenges in Modernizing Nuclear Power Plant Control Rooms,” at the 2024 Human Systems Symposium. Experts conducting human factors and human systems research will gather and share research at this conference. This conference is a good opportunity to develop new business for INL via research collaborations, as attendees exchange knowledge and explore the latest trends, advancements, and challenges in the field of human systems research across the DOE national laboratories.

99 GENERAL AND MISCELLANEOUS↗

DOE OSTI2025

Challenges in predicting protein-protein interactions of understudied viruses: Arenavirus-human interactions

Understanding protein-protein interactions (PPIs) between viruses and host organisms is crucial for uncovering infection mechanisms and identifying potential therapeutic targets. The ability to generalize PPI predictive models across understudied viruses presents a significant challenge. In this work, we use arenavirus-human PPIs to illustrate the difficulties associated with model generalization, which are compounded by a lack of both positive and negative data. We employ a Transfer Learning approach to investigate arenavirus-human PPIs by utilizing models trained on better-studied virus-human and human-human PPIs. Additionally, we curate and assess four types of negative sampling datasets to evaluate their impact on model performance. Despite the overall high accuracies (93–99 %) and AUPRC scores (0.8–0.9) appearing promising, further analysis indicates that these performance metrics can be misleading due to data leakage, data bias, and overfitting, especially concerning under-represented viral proteins. We reveal these gaps and assess the impact of data imbalance using standard k-fold cross-validation and Independent Blind Testing with a Balanced Dataset, resulting in a drop in accuracy below 50 %. We propose a viral protein-specific evaluation framework that categorizes viral proteins into majority and minority classes based on their representation in the dataset, enabling comparison of model performance across these groups using balanced accuracies. This framework offers a more robust evaluation of model generalizability, addressing biases inherent in standard evaluation techniques and paving the way for more reliable PPI prediction models for understudied viruses.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2025

Characterization of the procoagulant phenotype of amniotic fluid across gestation in rhesus macaques and humans

Background: Amniotic fluid (AF) plays a key role in fetal development, yet the evolving composition of AF and its effects of hemostasis and thrombosis are poorly understood. Objectives: Here, we aim to determine how the evolving molecular composition of AF relates to its procoagulant properties. Methods: We analyzed the proteomes, lipidomes and procoagulant properties of AF obtained by amniocentesis from rhesus macaque and human pregnancies at gestational-age matched timepoints. Results When added to human plasma, both rhesus and human AF accelerated clotting time and fibrin generation. We identified proteomic modules associated with clotting time and enriched for coagulation-related pathways. Proteins known to be involved in hemostasis were highly correlated with each other and their intensity of expression varied across gestation in both rhesus and humans. Inhibition of contact pathway did not affect the procoagulant effect of AF. Blocking tissue factor pathway inhibitor reversed the ability of AF to block the generation of FXa. The prothrombinase activity of AF was inhibited by phospholipid inhibitors. The levels of phosphatidylserine in AF were inversely correlated with clotting time. AF promoted platelet activation and secretion in plasma. Conclusions: The addition of AF to plasma enhances coagulation in a manner dependent on phospholipids as well as the presence of proteases and other proteins that directly regulate coagulation. We describe a correlation between clotting time and expression of coagulation proteins and phosphatidylserine in both rhesus and human AF, supporting the use rhesus models for future studies of AF biology.

amniotic fluid↗

DOE OSTI2025

A physiologically based pharmacokinetic (PBPK) model to align dosimetry of the isobutyl metabolic series in rats and humans

Here, we developed a physiologically based pharmacokinetic (PBPK) model in rats and humans for the isobutyl metabolic series including isobutyl acetate, isobutanol, isobutyraldehyde, and isobutyric acid. Chemical manufactures routinely use these compounds as solvents, for chemical synthesis, as potential biofuels, de-icing fluids, and additives for food and/or fragrance in consumer products. Human exposure to isobutyl compounds can occur through inhalation or oral routes. We previously developed a PBPK model for the propyl metabolic series and utilized it as a framework to create the isobutyl PBPK model due to the chemical similarities between the two series. To support model development, we measured in vitro metabolism of isobutyl acetate in rat and human blood and liver S9 fractions. Compared to rats, humans demonstrated faster isobutyl acetate hydrolysis in liver S9 fractions, while the hydrolysis rates in blood were similar between the two species. We used concentrations of isobutyl compounds measured in air and blood from rats exposed to isobutyl acetate and isobutanol as well as other published data to further parameterize the model. Following exposure to either isobutyl acetate or isobutanol, we observed isobutanol concentrations highest among the isobutyl compounds in the blood of rats. Overall, the model accurately predicts measured time course concentrations of isobutyl acetate, isobutanol, and isobutyric acid in available data in rats and humans. Sensitivity analyses identified alveolar ventilation rates, isobutyl metabolism rates, and cardiac output as the most sensitive parameters affecting concentrations of isobutyl compounds in blood. The isobutyl PBPK model enables comparisons of internal dose metrics across various isobutyl compound exposures and species and allows for calculation of equivalent external exposures that result in the same dose metric. Regulators can employ this PBPK model to predict and align internal dose metrics of isobutyl compounds for risk assessment purposes.

2-methyl-1-propanol↗

DOE OSTI2025

Dual Inhibitors of SARS-CoV-2 3CL Protease and Human Cathepsin L Containing Glutamine Isosteres Are Anti-CoV-2 Agents

SARS-CoV-2 3CL protease (Main protease) and human cathepsin L are proteases that play unique roles in the infection of human cells by SARS-CoV-2, the causative agent of COVID-19. Both proteases recognize leucine and other hydrophobic amino acids at the P 2 position of a peptidomimetic inhibitor. At the P 1 position, cathepsin L accepts many amino acid side chains, with a partial preference for phenylalanine, while 3CL-PR protease has a stringent specificity for glutamine or glutamine analogues. We have designed, synthesized, and evaluated peptidomimetic aldehyde dual-target (dual-acting) inhibitors using two peptide scaffolds based on those of two Pfizer 3CL-PR inhibitors, Nirmatrelvir, and PF-835321. Our inhibitors contain glutamine isosteres at the P 1 position, including 2-pyridon-3-yl-alanine, 3-pyridinyl-alanine, and 1,3-oxazo-4-yl-alanine groups. Inhibition constants for these new inhibitors ranged from K i = 0.6–18 nM (cathepsin L) and K i = 2.6–124 nM (3CL-PR), for which inhibitors with the 2-pyridon-3-yl-alanal substituent were the most potent for 3CL-PR. The anti-CoV-2 activity of these inhibitors ranged from EC 50 = 0.47–15 μM. X-ray structures of the peptidomimetic aldehyde inhibitors of 3CL-PR with similar scaffolds all demonstrated the formation of thiohemiacetals with Cys 145 , and hydrogen-bonding interactions with the heteroatoms of the pyridon-3-yl-alanyl group, as well as the nitrogen of the N-terminal indole and its appended carbonyl group at the P 3 position. The absence of these hydrogen bonds for the inhibitors containing the 3-pyridinyl-alanyl and 1,3-oxazo-4-yl-alanyl groups was reflected in the less potent inhibition of the inhibitors with 3CL-PR. In summary, our studies demonstrate the value of a second generation of cysteine protease inhibitors that comprise a single agent that acts on both human cathepsin L and SARS-CoV-2 3CL protease. Such dual-target inhibitors will provide anti-COVID-19 drugs that remain active despite the development of resistance due to mutation of the viral protease. Such dual-target inhibitors are more likely to remain useful therapeutics despite the emergence of inactivating mutations in the viral protease because the human cathepsin L will not develop resistance. This particular dual-target approach is innovative since one of the targets is viral (3CL-PR) required for viral protein maturation and the other is human (hCatL) which enables viral infection.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2025

Structural differences between human and mouse neurons and their implementation in generative AIs

Mouse and human brains have different functions that depend on their neuronal networks. We analyzed nanometer-scale three-dimensional structures of brain tissues of the mouse medial prefrontal cortex and compared them with structures of the human anterior cingulate cortex. The obtained results indicated that mouse neuronal somata are smaller and neurites are thinner than those of human neurons. We implemented these characteristics of mouse neurons in convolutional layers of a generative adversarial network (GAN) and a denoising diffusion implicit model (DDIM), which were then subjected to image generation tasks using photo datasets of cat faces, cheese, human faces, birds, and automobiles. The mouse-mimetic GAN outperformed a standard GAN in the image generation task using the cat faces and cheese photo datasets, but underperformed for human faces and birds. The mouse-mimetic DDIM gave similar results, suggesting that the nature of the datasets affected the results. Analyses of the five datasets indicated differences in their image entropy, which should influence the number of parameters required for image generation. The preferences of the mouse-mimetic AIs coincided with the impressions commonly associated with mice. The relationship between the neuronal network and brain function should be investigated by implementing other biological findings in artificial neural networks.

generative AI↗

DOE OSTI2025

Breaking the barrier of human-annotated training data for machine learning-aided plant research using aerial imagery

Machine learning (ML) can accelerate biological research. However, the adoption of such tools to facilitate phenotyping based on sensor data has been limited by (i) the need for a large amount of human-annotated training data for each context in which the tool is used and (ii) phenotypes varying across contexts defined in terms of genetics and environment. This is a major bottleneck because acquiring training data is generally costly and time-consuming. This study demonstrates how a ML approach can address these challenges by minimizing the amount of human supervision needed for tool building. A case study was performed to compare ML approaches that examine images collected by an uncrewed aerial vehicle to determine the presence/absence of panicles (i.e. “heading”) across thousands of field plots containing genetically diverse breeding populations of 2 Miscanthus species. Automated analysis of aerial imagery enabled the identification of heading approximately 9 times faster than in-field visual inspection by humans. Leveraging an Efficiently Supervised Generative Adversarial Network (ESGAN) learning strategy reduced the requirement for human-annotated data by 1 to 2 orders of magnitude compared to traditional, fully supervised learning approaches. The ESGAN model learned the salient features of the data set by using thousands of unlabeled images to inform the discriminative ability of a classifier so that it required minimal human-labeled training data. This method can accelerate the phenotyping of heading date as a measure of flowering time in Miscanthus across diverse contexts (e.g. in multistate trials) and opens avenues to promote the broad adoption of ML tools.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2024

Evaluating the impact of anatomical and physiological variability on human equivalent doses using PBPK models

Abstract Addressing human anatomical and physiological variability is a crucial component of human health risk assessment of chemicals. Experts have recommended probabilistic chemical risk assessment paradigms in which distributional adjustment factors are used to account for various sources of uncertainty and variability, including variability in the pharmacokinetic behavior of a given substance in different humans. In practice, convenient assumptions about the distribution forms of adjustment factors and human equivalent doses (HEDs) are often used. Parameters such as tissue volumes and blood flows are likewise often assumed to be lognormally or normally distributed without evaluating empirical data for consistency with these forms. In this work, we performed dosimetric extrapolations using physiologically based pharmacokinetic (PBPK) models for dichloromethane (DCM) and chloroform that incorporate uncertainty and variability to determine if the HEDs associated with such extrapolations are approximately lognormal and how they depend on the underlying distribution shapes chosen to represent model parameters. We accounted for uncertainty and variability in PBPK model parameters by randomly drawing their values from a variety of distribution types. We then performed reverse dosimetry to calculate HEDs based on animal points of departure for each set of sampled parameters. Corresponding samples of HEDs were tested to determine the impact of input parameter distributions on their central tendencies, extreme percentiles, and degree of conformance to lognormality. This work demonstrates that the measurable attributes of human variability should be considered more carefully and that generalized assumptions about parameter distribution shapes may lead to inaccurate estimates of extreme percentiles of HEDs.

Toxicology↗