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At least 109 records · Page 6

Performance Data Errors in Air Carrier Operations: Causes and Countermeasures

Several airline accidents have occurred in recent years as the result of erroneous weight or performance data used to calculate V-speeds, flap/trim settings, required runway lengths, and/or required climb gradients. In this report we consider 4 recent studies of performance data error, report our own study of ASRS-reported incidents, and provide countermeasures that can reduce vulnerability to accidents caused by performance data errors. Performance data are generated through a lengthy process involving several employee groups and computer and/or paper-based systems. Although much of the airline indUStry 's concern has focused on errors pilots make in entering FMS data, we determined that errors occur at every stage of the process and that errors by ground personnel are probably at least as frequent and certainly as consequential as errors by pilots. Most of the errors we examined could in principle have been trapped by effective use of existing procedures or technology; however, the fact that they were not trapped anywhere indicates the need for better countermeasures. Existing procedures are often inadequately designed to mesh with the ways humans process information. Because procedures often do not take into account the ways in which information flows in actual flight ops and time pressures and interruptions experienced by pilots and ground personnel, vulnerability to error is greater. Some aspects of NextGen operations may exacerbate this vulnerability. We identify measures to reduce the number of errors and to help catch the errors that occur.

countermeasures↗

Medical countermeasures for extraterrestrial environments: Current status and future prospects with focus on acute injuries

In all space exploratory activities involving humans there are associated risks to health and well-being. Exposure to ionizing radiation represents one of the more serious health concerns. Although medical issues can arise shortly following the rare acute exposures, the more likely radiation-associated injuries will manifest in a delayed fashion following sub-acute exposures or protracted exposures to relatively low radiation doses. The radiological conditions that present these health risks during extraterrestrial space travel are presented in this article, along with current physical and medical countermeasures for such exposure contingencies. The aim of this article is to discuss radiation medical countermeasures that may be considered for future space exploration and travel. Biomedical advances have occurred toward the control and minimization of acute, sub-acute, and fractionated radiation exposure injuries, whether they stem from intentional application of radio-therapeutic procedures or unintentional, accidental terrestrial-based exposures. Those advances, based largely on novel bioengineering, genetic, and combinatorial pharmaceutical strategies, are briefly reviewed here, along with the promising prospects of additional, new and improved medical countering systems/agents that will be forthcoming with additional research and development efforts.

Acute/chronic radiation injuries↗

Biological Space Radiation Countermeasures to Enable Long Duration Exploration Missions

NASA’s career radiation limit for astronauts is 600 mSv. Currently planned missions beyond low Earth orbit (LEO) will expose crew to at least double that amount of radiation (for Mars missions). Therefore, to enable long duration exploration, countermeasures need to be deployed to reduce the long-term health outcomes of space radiation exposure. Limitations to the ability of spacecraft to shield against the high energy charged particles of the space radiation environment necessitate alternative methods to reduce overall space radiation risk for carcinogenesis. Recent successes in the arenas of Acute Radiation Syndrome (ARS) and clinical radiotherapy have demonstrated the efficacy of compound-based/biologicals in reducing the detrimental long term health outcomes associated with space radiation exposure. In recent years, the Space Radiation Element has funded the investigation of several such compounds including Avasopasem Manganese, CDDO-Me, Metformin, and γ-tocotrienol. The demonstrated efficacy of these compounds in reducing carcinogenesis, central nervous system, and cardiovascular disease risks demonstrate the need for, and potential benefit of, a robust countermeasure identification and development program with an initial starting suite of compounds available to validate others. The authors would also like to present highlights of a recent Space Radiation Element sponsored issue of Life Sciences in Space Research entitled “Breaking the Limit” on this specific topic.

Space Radiation↗

Biological Space Radiation Countermeasures to Enable Long Duration Exploration Missions

NASA’s career radiation limit for astronauts is 600 mSv. Currently planned missions beyond low Earth orbit (LEO) will expose crew to at least double that amount of radiation (for Mars missions). Therefore, to enable long duration exploration, countermeasures need to be deployed to reduce the long-term health outcomes of space radiation exposure. Limitations to the ability of spacecraft to shield against the high energy charged particles of the space radiation environment necessitate alternative methods to reduce overall space radiation risk for carcinogenesis. Recent successes in the arenas of Acute Radiation Syndrome (ARS) and clinical radiotherapy have demonstrated the efficacy of compound-based/biologicals in reducing the detrimental long term health outcomes associated with space radiation exposure. In recent years, the Space Radiation Element has funded the investigation of several such compounds including Avasopasem Manganese, CDDO-Me, Metformin, and γ-tocotrienol. The demonstrated efficacy of these compounds in reducing carcinogenesis, central nervous system, and cardiovascular disease risks demonstrate the need for, and potential benefit of, a robust countermeasure identification and development program with an initial starting suite of compounds available to validate others. The authors would also like to present highlights of a recent Space Radiation Element sponsored issue of Life Sciences in Space Research entitled “Breaking the Limit” on this specific topic.

Space Radiation↗

Astronaut Physiological Deconditioning and Exercise Prescription Countermeasures in Spaceflight

The human skeletal muscular and cardiovascular systems are adapted to the upright posture of Earth’s gravitational environment. Astronauts experience an altered gravity environment in spaceflight that leads to a number of physiological changes and decrements to these systems that can decrease overall crew performance. Countermeasures, including prescribed exercise during spaceflight, is vital for astronauts to maintain optimal health and performance. The degree of physiological deconditioning is dependent on a multitude of factors such as sex, age, mission duration, fitness level, and gravity environments experienced. Deconditioning begins immediately upon entering an altered gravity environment and physiological decrements of the skeletal muscular and cardiovascular systems are measurable among astronauts within a few days. Thus, to maintain their physical fitness, ability to perform mission duties, and be able to egress vehicles when needed, it is imperative that astronauts participate in exercise during all phases of flight. This is especially important for long duration flights where deconditioning effects can be more deleterious. The NASA Office of the Chief Health and Medical Officer 3001 Standards Team develops requirements utilized by commercial and international partners to better understand spaceflight-induced physiological changes and countermeasures and expected outcomes with or without exercise.

exercise physiology↗

Model acetylcholinesterase‐Fc fusion glycoprotein biotechnology system for the manufacture of an organophosphorus toxicant bioscavenging countermeasure

Abstract Organophosphate (OP) toxicants remain an active threat to public health and to warfighters in the military. Current countermeasures require near immediate administration following OP exposure and are reported to have controversial efficacies. Acetylcholinesterase (AChE) fused to the human immunoglobulin 1 (IgG1) Fc domain (AChE‐Fc) is a potential bioscavenger for OP toxicants, but a reproducible AChE‐Fc biomanufacturing strategy remains elusive. This report is the first to establish a comprehensive laboratory‐scale bioprocessing strategy that can reproducibly produce AChE‐Fc and AChE(W86A)‐Fc which is a mutated AChE protein with reduced enzymatic activity. Characterization studies revealed that AChE‐Fc and AChE(W86A)‐Fc are N ‐glycosylated dimeric fusion glycoproteins but only AChE‐Fc had the capability to bind to paraoxon (a model OP). This AChE‐Fc fusion glycoprotein bioprocessing strategy can be leveraged during industrial biomanufacturing development, while the research‐grade AChE‐Fc proteins can be used to determine the potential clinical relevance of the countermeasure against OP toxicants.

Biel, Thomas G.↗

Countermeasures for Preventing and Treating Opioid Overdose

The only medication available currently to prevent and treat opioid overdose (naloxone) was approved by the US Food and Drug Administration (FDA) nearly 50 years ago. Due to its pharmacokinetic and pharmacodynamic properties, naloxone has limited utility under some conditions and would not be effective to counteract mass casualties involving large-scale deployment of weaponized synthetic opioids. To address shortcomings of current medical countermeasures for opioid toxicity, a trans-agency scientific meeting was convened by the US National Institute of Allergy and Infectious Diseases/National Institutes of Health (NIAID/NIH) on August 6 and 7, 2019, to explore emerging alternative approaches for treating opioid overdose in the event of weaponization of synthetic opioids. The meeting was initiated by the Chemical Countermeasures Research Program (CCRP), was organized by NIAID, and was a collaboration with the National Institute on Drug Abuse/NIH (NIDA/NIH), the FDA, the Defense Threat Reduction Agency (DTRA), and the Biomedical Advanced Research and Development Authority (BARDA). This paper provides an overview of several presentations at that meeting that discussed emerging new approaches for treating opioid overdose, including the following: (1) intranasal nalmefene, a competitive, reversible opioid receptor antagonist with a longer duration of action than naloxone; (2) methocinnamox, a novel opioid receptor antagonist; (3) covalent naloxone nanoparticles; (4) serotonin (5-HT)1A receptor agonists; (5) fentanyl-binding cyclodextrin scaffolds; (6) detoxifying biomimetic “nanosponge” decoy receptors; and (7) antibody-based strategies. These approaches could also be applied to treat opioid use disorder.

59 BASIC BIOLOGICAL SCIENCES↗

Characterization of two affinity matured Anti-Yersinia pestis F1 human antibodies with medical countermeasure potential

Yersinia pestis , the causative agent of plague and a biological threat agent, presents an urgent need for novel medical countermeasures due to documented cases of naturally acquired antibiotic resistance and potential person-to-person spread during a pneumonic infection. Immunotherapy has been proposed as a way to circumvent current and future antibiotic resistance. Here, we describe the development and characterization of two affinity matured human antibodies (αF1Ig AM2 and αF1Ig AM8) that promote survival of mice after exposure to aerosolized Y . pestis . We share details of the error prone PCR and yeast display technology-based affinity maturation process that we used. The resultant matured antibodies have nanomolar affinity for Y . pestis F1 antigen, are produced in high yield, and are resilient to 37°C stress for up to 6 months. Importantly, in vitro assays using a murine macrophage cell line demonstrated that αF1Ig AM2 and αF1Ig AM8 are opsonic. Even more importantly, in vivo studies using pneumonic plague mouse models showed that 100% of the mice receiving 500 μg of IgGs αF1Ig AM2 and αF1Ig AM8 survived lethal challenge with aerosolized Y . pestis CO92. Combined, these results provide evidence of the quality and robustness of αF1Ig AM2 and αF1Ig AM8 and support their development as potential medical countermeasures against plague.

59 BASIC BIOLOGICAL SCIENCES↗

Design, Detection, and Countermeasure of Frequency Spectrum Attack and Its Impact on Long Short-Term Memory Load Forecasting and Microgrid Energy Management

This paper introduces a frequency-domain false data injection attack called Frequency Spectrum Attack (FSA) and explores its effects on load forecasting and the energy management system (EMS) in a microgrid. The FSA analyzes time-series signals in the frequency domain to identify patterns in their frequency spectrum. It learns the distribution of dominant frequencies in a dataset of healthy signals. Subsequently, it manipulates the amplitudes of dominant frequencies within this healthy distribution, ensuring a stealthy attack against statistical analysis of the signal spectrum. We evaluated the performance of FSA on LSTM, a state-of-the-art network for load forecasting. The results show that FSA can triple the Mean Absolute Error (MAE) of predictions compared to the normal case and increase it by 70% compared to noise injection attacks. Furthermore, FSA indirectly enhances battery utilization in the EMS by 45%. We then proposed a detection method that combines statistical analysis and machine-learning-based classification techniques with features. The model effectively distinguishes FSA from healthy and noisy signals, achieving an accuracy of 98.7% and an F1-score of 98.1% on a load dataset, covering healthy, FSA, and noisy load data. Finally, a countermeasure was introduced based on the statistical analysis of the frequency spectrum of healthy signals to mitigate the impact of FSA. This countermeasure successfully reduces the MAE of the attacked model from 0.135 to 0.053, validating its effectiveness in mitigating FSA.

Nazeri, Amirhossein↗

Characterization of Humanized Mouse Model of Organophosphate Poisoning and Detection of Countermeasures via MALDI-MSI

Organophosphoate (OP) chemicals are known to inhibit the enzyme acetylcholinesterase (AChE). Studying OP poisoning is difficult because common small animal research models have serum carboxylesterase, which contributes to animals’ resistance to OP poisoning. Historically, guinea pigs have been used for this research; however, a novel genetically modified mouse strain (KIKO) was developed with nonfunctional serum carboxylase (Es1 KO) and an altered acetylcholinesterase (AChE) gene, which expresses the amino acid sequence of the human form of the same protein (AChE KI). KIKO mice were injected with 1xLD50 of an OP nerve agent or vehicle control with or without atropine. After one to three minutes, animals were injected with 35 mg/kg of the currently fielded Reactivator countermeasure for OP poisoning. Postmortem brains were imaged on a Bruker RapifleX ToF/ToF instrument. Data confirmed the presence of increased acetylcholine in OP-exposed animals, regardless of treatment or atropine status. More interestingly, we detected a small amount of Reactivator within the brain of both exposed and unexposed animals; it is currently debated if reactivators can cross the blood–brain barrier. Further, we were able to simultaneously image acetylcholine, the primary affected neurotransmitter, as well as determine the location of both Reactivator and acetylcholine in the brain. This study, which utilized sensitive MALDI-MSI methods, characterized KIKO mice as a functional model for OP countermeasure development.

2-PAM↗

Space Station requirements for in-flight exercise countermeasures

In an effort to retard the deleterious effects of space adaptation, NASA has defined requirements for an Exercise Countermeasure Facility (ECF) within the Space Station Crew Health Care System (CHeCS). The application of exercise as a countermeasure to spaceflight-induced deconditioning has been utilized in the past by both the United States and the Soviet space programs. The ECF will provide exercise hardware, physiological monitoring capabilities, and an interactive motivational display system. ECF operations and data will be coupled through the Space Station Freedom Data Management System for monitoring of inflight training and testing from ground control, thus allowing for real-time evaluation of crewmember performance and modification of exercise prescriptions. Finally, the objective of the ECF is to monitor and control the exercise of crewmembers for the maintenance of an operational level of fitness to ensure mission success.

Hayes, Judith C.↗

Countermeasures for mitigating the effects of global environment changes

Environmental countermeasures for preventing the negative effects of global climate change and ozone depletion are discussed with special emphasis on the possibilities of space-based actions. Among the programs addressed are the Mission to Planet Earth, the Solar Power Satellite (and linkage to the Space Exploration Initiative), and proposed projects such as a lunar-based power generator that utilizes He-3 as a fusion fuel when combined with deuterium. The concept of regional working groups is proposed for initiating the programs for effective countermeasures.

Jenkins, Lyle M.↗

The role of pyridoxine as a countermeasure for in-flight loss of lean body mass

Ground based and in flight research has shown that humans, under conditions of microgravity, sustain a loss of lean body tissue (protein) and changes in several biological processes including, reductions in red blood cell mass, and neurotransmitters. The maintenance of muscle mass, the major component of lean body mass, is required to meet the needs of space station EVAs. Central to the biosynthesis of amino acids, the building blocks of protein, is pyridoxine (vitamin B-6). Muscle mass integrity requires the availability of vitamin B-6 for protein metabolism and neurotransmitter synthesis. Furthermore, the formation of red blood cells require pyridoxine as a cofactor in the biosynthesis of hemoglobin, a protein that carries oxygen to tissues. In its active form, pyridoxal-5'-phosphate (PLP), vitamin B-6 serves as a link between amino acid and carbohydrate metabolism through intermediates of glycolysis and the tricarboxylic acid cycle. In addition to its role in energy metabolism, PLP is involved in the biosynthesis of hemoglobin and neurotransmitter which are necessary for neurological functions. Alterations in pyridoxine metabolism may affect countermeasures designed to overcome some of these biochemical changes. The focus of this research is to determine the effects of microgravity on the metabolic utilization of vitamin B-6, integrating nutrition as an integral component of the countermeasure (exercise) to maintain lean body mass and muscle strength. The objectives are: 1) to determine whether microgravity effects the metabolic utilization of pyridoxine and 2) to quantitate changes in B-6 vitamer distribution in tissue and excreta relative to loss of lean body tissue. The rationale for this study encompasses the unique challenge to control biochemical mechanisms effected during space travel and the significance of pyridoxine to maintain and counter muscle integrity for EVA activities. This experiment will begin to elucidate the importance of biochemical interactions between micronutrients and the homeostasis condition of biological processes in the space environment. To address this research topic a simulated microgravity model has been developed. The experiment uses radioisotopically labelled pyridoxine administered as an oral dose to rats which are maintained by tail suspension to simulate a microgravity environment. At the termination of the study, liver, muscle, blood and urine are collected and analyzed by reverse phase high pressure liquid chromatography to determine the quantity and distribution of the B-6 vitamers in tissue and excreta relative to lean body tissue loss. Earlier studies, published by this investigator, have shown that differences in vitamer distribution among samples from experimental versus control subjects indicate changes in metabolic utilization and storage of vitamin B-6.

Gilbert, Joyce A.↗

Development of lower body negative pressure as a countermeasure for orthostatic intolerance

Exposure to prolonged (1-4 hr) lower body negative pressure (LBNP) is a countermeasure against postflight orthostatic intolerance which is used in the Soviet space program and planned for use in the American space program. LBNP in combination with fluid-loading is believed to act by promoting a transient positive fluid balance resulting in an increase in vascular, as well as extravascular fluid. Inflight LBNP also may provide beneficial orthostatic effects by restoring baroreceptor reflex functions and/or lower body venous compliance. Current research efforts at the Johnson Space Center are directed toward increasing the effectiveness and efficiency of the LBNP and saline countermeasure. A promising avenue may involve combining pharmacologic agents, such as inhaled anti-diuretic hormone, or mineralocorticoids, with mechanical stimuli such as LBNP.

Fortney, Suzanne M.↗

Countermeasure for reducing post-flight orthostatic intolerance: Lower Body Negative Pressure (LBNP) experiment E140

Investigators have shown that after 1-2 weeks of bed rest ingestion of 1000 ml of a salt water solution during 4 hours of continuous exposure to 30 mm Hg of lower body negative pressure will protect plasma volume and orthostatic function for up to 24 hours. We hypothesize that a similar countermeasure will reduce the effects of fluid loss induced by headward fluid shift during space flight. The objective of this flight experiment is to evaluate the efficacy of the proposed countermeasure in reversing these effects on the cardiovascular system. Lower Body Negative Pressure (LBNP) involves exposing the legs and lower abdomen to reduced air pressure. The LBNP device is an air-tight chamber that seals the subject's waist to enclose the lower body. As used in this experiment, LBNP provides both the candidate treatment as well as the means of assessing the effectiveness of the treatment.

Charles, John B.↗

Circadian countermeasures for shiftworkers during USMP-2: A report to mission management

People who must work at night experience a number of physiological and psychological difficulties. These include sleepiness and fatigue at work, poor daytime sleep, gastrointestinal distress, impaired concentration and performance, disturbed mood, and increased health complaints and risk of disease. These difficulties arise because nocturnal work and daytime sleep take place at inappropriate phases of the body's circadian rhythms. Intense artificial light can shift the phase of human circadian rhythms, and can thus be used to promote adaptation to shifted work schedules. The first attempts to investigate the efficacy of light treatment for MSFC POCC shiftworkers took place during USML-1 and ATLAS-2. The findings from these studies led to the development of a Circadian Countermeasures Program that was implemented during USMP-2. Light treatment and other circadian countermeasures were employed to promote adjustment to mission shiftwork in POCC cadre volunteers. Treatment protocols were designed and customized for each volunteer's work hours and personal preferences. Treatment protocols included some or all of the following: scheduled self-administration of intense light, scheduled avoidance or attenuation of sunlight at other times, and sleep schedules. Data from post-mission questionnaires indicated that volunteers found the program to be effective, convenient, and beneficial.

Stewart, Karen T.↗

Comparison of saline and fludrocortisone as fluid-loading countermeasures following exposure to simulated microgravity

Saline loading (SL) within hours of reentry is currently used as a countermeasure against postflight orthostatic hypotension in astronauts. However, its effects on blood volume expansion is not quantified and its effectiveness has proved marginal at best. The purposes of the present study were: (1) to quantify the effects of SL on plasma volume and orthostatic tolerance following exposure to simulated microgravity and (2) to compare these effects with the use of a pharacological fluid expander, fludrcortisone (F). Method: Eleven men (30-45 yr.) underwent a 15-minute stand test before and immediately after 7 days of head-down bedrest (BR). Five subjects ingested SL (8 g salt tablets with 1 liter of water) 2 hours before standing at the end of BR while the other 6 subjects received 0.2 mg oral doses of F at 0800 and 2200 hours the day before and 0800 hours the day the subjects got out of bed (i.e., 2 hours before standing). Plasma volume (PV) was measured before BR on day 7 of BR and after the final SL and F treatments just before the post-BR stand test. Blood pressure and heart rate were measured continuously during the stand tests. Results: BR decreased PV from 40.7 plus or minus 1.9 mml/kg to 35.9 plus or minus 1.1 ml/kg (minus 11.8 percent P less than 0.05). Following SL, PV remained at 36.4 plus or minus 1.5 ml/kg while F returned PV to 39.1 plus or minus 1.8 ml/kg. The post BR stand test was completed without syncopal symptoms by 5 of 6 F subjects but only 2 of 5 SL subjects. Conclusions: SL may be ineffective in restoring PV to preflight levels and may provide inadequate protection against postflight orthostatic hypotension. In contrast, F may provide a promising countermeasure since it restored PV and reduced the incidence of syncope following exposure to simulated microgravity in the present study.

Vernikos, J.↗

Alterations in Skeletal Muscle With Disuse Atrophy: The Effects of Countermeasures

The specific aims of this project concerned three general areas: (1) studies on the contractile function of single skinned fibers designed to determine the time course and cellular basis of the Hindlimb Suspension (HS) induced increase in fiber Vo (maximal shortening velocity), and the decrease in peak tension (Po); (2) studies designed to understand the effect of HS on single fiber substrate utilization during contractile activity, and how if at all such changes contribute to the increased muscle fatigue associated with HS; and (3) studies evaluating the effectiveness of standing and ladder climbing as countermeasures to the deleterious effects of HS. We have constructed all of the necessary equipment, and are currently conducting preliminary studies on T-tubular charge movement. A list of publications from this contract is included at the end of this report. The three objectives are (1) Functional Studies on the Single Skinned Fiber; (2) Fiber Substrate Utilization and Muscle Fatugue with Contracting Activity and (3) Exercise Countermeasures.

Fitts, Robert H.↗