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At least 289 records · Page 16

Predicted success of prophylactic antiviral therapy to block or delay SARS-CoV-2 infection depends on the drug's mechanism of action

Repurposed drugs that are safe and immediately available constitute a first line of defense against new viral infections. Despite limited antiviral activity against SARS-CoV-2, several drugs are being tested as medication or as prophylaxis to prevent infection. Using a stochastic model of early phase infection, we evaluate the success of prophylactic treatment with different drug types to prevent viral infection. We find that there exists a critical efficacy that a treatment must reach in order to block viral establishment. Treatment by a combination of drugs reduces the critical efficacy, most effectively by the combination of a drug blocking viral entry into cells and a drug increasing viral clearance. Below the critical efficacy, the risk of infection can nonetheless be reduced. Drugs blocking viral entry into cells or enhancing viral clearance reduce the risk of infection more than drugs that reduce viral production in infected cells. The larger the initial inoculum of infectious virus, the less likely is prevention of an infection. In our model, we find that as long as the viral inoculum is smaller than 10 infectious virus particles, viral infection can be prevented almost certainly with drugs of 90% efficacy (or more). Even when a viral infection cannot be prevented, antivirals delay the time to detectable viral loads. The largest delay of viral infection is achieved by drugs reducing viral production in infected cells. A delay of virus infection flattens the within-host viral dynamic curve, possibly reducing transmission and symptom severity. Thus, antiviral prophylaxis, even with reduced efficacy, could be efficiently used to prevent or alleviate infection in people at high risk.

59 BASIC BIOLOGICAL SCIENCES↗

Microbial Risk Assessment

Historically, microbiological spaceflight requirements have been established in a subjective manner based upon expert opinion of both environmental and clinical monitoring results and the incidence of disease. The limited amount of data, especially from long-duration missions, has created very conservative requirements based primarily on the concentration of microorganisms. Periodic reevaluations of new data from later missions have allowed some relaxation of these stringent requirements. However, the requirements remain very conservative and subjective in nature, and the risk of crew illness due to infectious microorganisms is not well defined. The use of modeling techniques for microbial risk has been applied in the food and potable water industries and has exceptional potential for spaceflight applications. From a productivity standpoint, this type of modeling can (1) decrease unnecessary costs and resource usage and (2) prevent inadequate or inappropriate data for health assessment. In addition, a quantitative model has several advantages for risk management and communication. By identifying the variable components of the model and the knowledge associated with each component, this type of modeling can: (1) Systematically identify and close knowledge gaps, (2) Systematically identify acceptable and unacceptable risks, (3) Improve communication with stakeholders as to the reasons for resource use, and (4) Facilitate external scientific approval of the NASA requirements. The modeling of microbial risk involves the evaluation of several key factors including hazard identification, crew exposure assessment, dose-response assessment, and risk characterization. Many of these factors are similar to conditions found on Earth; however, the spaceflight environment is very specialized as the inhabitants live in a small, semi-closed environment that is often dependent on regenerative life support systems. To further complicate modeling efforts, microbial dose-response characteristics may be affected by a potentially dysfunctional crew immune system during a mission. In addition, microbial virulence has been shown to change under certain conditions during spaceflight, further complicating dose-response characterization. An initial study of the applicability of microbial risk assessment techniques was performed using Crew Health Care System (CHeCS) operational data from the International Space Station potable water systems. The risk of infection from potable water was selected as the flight systems and microbial ecology are well defined. This initial study confirmed the feasibility of using microbial risk assessment modeling for spaceflight systems. While no immediate threat was detected, the study identified several medically significant microorganisms that could pose a health risk if uncontrolled. The study also identified several specific knowledge gaps in making a risk assessment and noted that filling these knowledge gaps is essential as the risk estimates may change by orders of magnitude depending on the answers. The current phase of the microbial risk assessment studies focuses on the dose-response relationship of specific infectious agents, focusing on Salmonella enterica Typhimurium, Pseudomonas spp., and Escherichia coli, as their evaluation will provide a better baseline for determining the overall hazard characterization. The organisms were chosen as they either have been isolated on spacecraft or have an identified route of infection during a mission. The characterization will utilize dose-response models selected either from the peer-reviewed literature and/or by using statistical approaches. Development of these modeling and risk assessment techniques will help to optimize flight requirements and to protect the safety, health, and performance of the crew.

Ott, C. M.↗

Comparison of Risk from Orbital Debris and Meteoroid Environment Models on the Extravehicular Mobility Unit (EMU)

A well-known hazard associated with exposure to the space environment is the risk of failure from an impact from a meteoroid and orbital debris (MMOD) particle. An extravehicular mobility unit (EMU) “spacesuit” impact during a US extravehicular activity (EVA) is of great concern as a large leak could prevent an astronaut from safely reaching the airlock in time resulting in a loss of life. A risk assessment is provided to the EVA office at the Johnson Space Center (JSC) by the Hypervelocity Impact Technology (HVIT) group prior to certification of readiness for each US EVA. Need to understand the effect of updated meteoroid and orbital debris environment models to EMU risk.

Hoffman, Kevin↗

Analytical Method to Evaluate Failure Potential During High-Risk Component Development

Communicating failure mode information during design and manufacturing is a crucial task for failure prevention. Most processes use Failure Modes and Effects types of analyses, as well as prior knowledge and experience, to determine the potential modes of failures a product might encounter during its lifetime. When new products are being considered and designed, this knowledge and information is expanded upon to help designers extrapolate based on their similarity with existing products and the potential design tradeoffs. This paper makes use of similarities and tradeoffs that exist between different failure modes based on the functionality of each component/product. In this light, a function-failure method is developed to help the design of new products with solutions for functions that eliminate or reduce the potential of a failure mode. The method is applied to a simplified rotating machinery example in this paper, and is proposed as a means to account for helicopter failure modes during design and production, addressing stringent safety and performance requirements for NASA applications.

Tumer, Irem Y.↗

Guide for Oxygen Compatibility Assessments on Oxygen Components and Systems

Understanding and preventing fire hazards is necessary when designing, maintaining, and operating oxygen systems. Ignition risks can be minimized by controlling heat sources and using materials that will not ignite or will not support burning in the end-use environment. Because certain materials are more susceptible to ignition in oxygen-enriched environments, a compatibility assessment should be performed before the component is introduced into an oxygen system. This document provides an overview of oxygen fire hazards and procedures that are consistent with the latest versions of American Society for Testing and Materials (ASTM) Standards G63 (1999) and G94 (2005) to address fire hazards associated with oxygen systems. This document supersedes the previous edition, NASA Technical Memorandum 104823, Guide for Oxygen Hazards Analyses on Components and Systems (1996). The step-by-step oxygen compatibility assessment method described herein (see Section 4) enables oxygen-system designers, system engineers, and facility managers to determine areas of concern with respect to oxygen compatibility and, ultimately, prevent damage to a system or injury to personnel.

Rosales, Keisa R.↗

Early Intervention Program Los Alamos National Laboratory [Slides]

Objectives of the Program: Identify employees with symptoms/discomfort and provide early intervention/rapid response before discomfort becomes an injury; Demonstrate to employees that the Laboratory cares about them using a personalized approach; Improve worker productivity and workplace satisfaction; Spread the word so that employees report discomfort early and rapid intervention can be executed to prevent injuries; facilitate procurement of necessary equipment as quickly as possible given risk of progression to injury.

99 GENERAL AND MISCELLANEOUS↗

Coronary Risk Factor Scoring as a Guide for Counseling

A risk factor scoring system for early detection, possible prediction, and counseling to coronary heart disease patients is discussed. Scoring data include dynamic EKG, cholesterol levels, triglycerine content, total lipid level, total phospolipid levels, and electrophoretic patterns. Results indicate such a system is effective in identifying high risk subjects, but that the ability to predict exceeds the ability to prevent heart disease or its complications.

Robert L. Fleck↗

SSME technology test bed fast shutdown assessment

The fastest practical shutdown sequence for the Technology Test Bed Engine is developed. A sequence is defined and key issues addressed. The conclusion of the study is that a fastest shutdown sequence within the existing SSME design capability is practical and can cut oxidizer consumption by 50 percent. However, the revised sequence would not have prevented any of the prior experienced SSME incidents and would introduce development risk to the program.

Liebman, A.↗

Wire insulation degradation and flammability in low gravity

This view-graph presentation covers the following topics: an introduction to spacecraft fire safety, concerns in fire prevention in low gravity, shuttle wire insulation flammability experiment, drop tower risk-based fire safety experiment, and experimental results, conclusions, and proposed studies.

Friedman, Robert↗

Compact, Reliable EEPROM Controller

A compact, reliable controller for an electrically erasable, programmable read-only memory (EEPROM) has been developed specifically for a space-flight application. The design may be adaptable to other applications in which there are requirements for reliability in general and, in particular, for prevention of inadvertent writing of data in EEPROM cells. Inadvertent writes pose risks of loss of reliability in the original space-flight application and could pose such risks in other applications. Prior EEPROM controllers are large and complex and do not provide all reasonable protections (in many cases, few or no protections) against inadvertent writes. In contrast, the present controller provides several layers of protection against inadvertent writes. The controller also incorporates a write-time monitor, enabling determination of trends in the performance of an EEPROM through all phases of testing. The controller has been designed as an integral subsystem of a system that includes not only the controller and the controlled EEPROM aboard a spacecraft but also computers in a ground control station, relatively simple onboard support circuitry, and an onboard communication subsystem that utilizes the MIL-STD-1553B protocol. (MIL-STD-1553B is a military standard that encompasses a method of communication and electrical-interface requirements for digital electronic subsystems connected to a data bus. MIL-STD- 1553B is commonly used in defense and space applications.) The intent was to both maximize reliability while minimizing the size and complexity of onboard circuitry. In operation, control of the EEPROM is effected via the ground computers, the MIL-STD-1553B communication subsystem, and the onboard support circuitry, all of which, in combination, provide the multiple layers of protection against inadvertent writes. There is no controller software, unlike in many prior EEPROM controllers; software can be a major contributor to unreliability, particularly in fault situations such as the loss of power or brownouts. Protection is also provided by a powermonitoring circuit.

Katz, Richard↗

C-Band Airport Surface Communications System Engineering-Initial High-Level Safety Risk Assessment and Mitigation

This document is being provided as part of ITT's NASA Glenn Research Center Aerospace Communication Systems Technical Support (ACSTS) contract: "New ATM Requirements--Future Communications, C-Band and L-Band Communications Standard Development." ITT has completed a safety hazard analysis providing a preliminary safety assessment for the proposed C-band (5091- to 5150-MHz) airport surface communication system. The assessment was performed following the guidelines outlined in the Federal Aviation Administration Safety Risk Management Guidance for System Acquisitions document. The safety analysis did not identify any hazards with an unacceptable risk, though a number of hazards with a medium risk were documented. This effort represents an initial high-level safety hazard analysis and notes the triggers for risk reassessment. A detailed safety hazards analysis is recommended as a follow-on activity to assess particular components of the C-band communication system after the profile is finalized and system rollout timing is determined. A security risk assessment has been performed by NASA as a parallel activity. While safety analysis is concerned with a prevention of accidental errors and failures, the security threat analysis focuses on deliberate attacks. Both processes identify the events that affect operation of the system; and from a safety perspective the security threats may present safety risks.

Zelkin, Natalie↗

Assessment of the State-of-the-Art of System-Wide Safety and Assurance Technologies

Since its initiation, the System-wide Safety Assurance Technologies (SSAT) Project has been focused on developing multidisciplinary tools and techniques that are verified and validated to ensure prevention of loss of property and life in NextGen and enable proactive risk management through predictive methods. To this end, four technical challenges have been listed to help realize the goals of SSAT, namely (i) assurance of flight critical systems, (ii) discovery of precursors to safety incidents, (iii) assuring safe human-systems integration, and (iv) prognostic algorithm design for safety assurance. The objective of this report is to provide an extensive survey of SSAT-related research accomplishments by researchers within and outside NASA to get an understanding of what the state-of-the-art is for technologies enabling each of the four technical challenges. We hope that this report will serve as a good resource for anyone interested in gaining an understanding of the SSAT technical challenges, and also be useful in the future for project planning and resource allocation for related research.

Roychoudhury, Indranil↗

A New Vision and A More Rational Process Will Advance Space Life Support Through Better Projects

Many space life support assumptions are obviously mistaken but they are generally accepted because they mutually support each other and because they advance a mistaken futuristic vision of closed human ecosystems in space. Many projects have been mistakenly selected to increase life support system closure or reduce launch mass in order to implement this impractical vision. Project members rarely challenge their project’s assumptions and guiding vision. Systems engineering including cost, reliability, risk, and system trade-offs has been very strongly discouraged to prevent rational criticism of these dubious assumptions, the projects, and the ecosystem vision. A more realistic vision can define better near term life support goals and future aspirations that will improve mission support and increase public interest. Given more realistic goals, it will be possible to develop effective technical alternatives, use open rational project selection methods, conduct professional project management, and make swifter progress in the inevitable human advance into space. The current unworkable human space settlement scenario involves moon visits and permanent bases, zero gravity trips to Mars, Mars visits and bases, all leading to extensive human settlements on the moon and Mars. This is unrealistic because the moon and Mars have less than Earth normal gravity and high radiation that can seriously damage human health. A better alternative would use rotating space colonies that produce Earth gravity and are radiation shielded. The attractive fantasy of reproducing terrestrial ecology in space should be replaced by the idea of building a closed system based on advancing technology such as artificial photosynthesis. Past mistaken projects include growing plants for food to replicate terrestrial food sources, recovering small amounts of water from difficult to process waste to achieve high system closure, and using newly designed, lighter, but unreliable hardware to reduce launch mass. The political process supporting the false assumptions, projects, and vision has deliberately prevented the usual systems engineering and cost-benefit analysis. We are going to do much better.

Harry W. Jones↗

A mechanistic model of a PWR-based nuclear power plant in response to external hazard-induced station blackout accidents

Natural hazard-induced nuclear accidents, such as the Fukushima Daiichi Accident that occurred in Japan in 2011, have significantly increased reactor safety studies in understanding nuclear power plant (NPP) responses to external hazard events such as earthquakes and floods. Natural hazards could cause the loss of offsite power in nuclear power plants, potentially leading to a Station Blackout (SBO) accident that significantly contributes to the overall risk of nuclear power plant accidents. Despite the fact that extensive research has been conducted on the station blackout accident for nuclear power plant, further understanding of these events is needed, particularly in the context of the dynamic nature of external hazards such as external flooding. This paper estimates the progression of station blackout events for a generic pressurized water reactor (PWR) in response to external flooding events. The original RELAP5-3D model of the Westinghouse four-loop design pressurized water reactor was adopted and modified to simulate the external flood-induced station blackout accident, including the short-term and long-term station blackout scenarios. A sensitivity analysis of long-term station blackout, examining reactor operation times and analyzing key parameters over time, was also conducted in this work. The results of the analyses, especially the critical timing parameters of key event sequences, provide useful insights about the time during the external flooding event, which is important for plant operators to make timely decisions to prevent potential core damage. This paper represents significant progress toward developing an integrated risk assessment framework for further identifying and assessing the effects of the critical sources of uncertainties of nuclear power plant under external hazard-induced events.

Liu, Tao↗

Establishing and Monitoring an Aseptic Workspace

When are aseptic operations necessary? In order to meet certain bioburden requirements, some components must undergo dry heat microbial reduction (DHMR) or other sterilizing procedures. If sensitive surfaces must be re-exposed after DHMR, this could compromise the bioburden levels. Recontaminating sterilized surfaces could be costly both in time by requiring repeated DHMR and risk to the hardware, which may not be compatible with repeated high temperature bakes. In order to prevent recontamination of the sensitive surfaces, an aseptic environment and sterile technique must be employed. Aseptic environments mean working in a space with almost no detectable bioburden in the air or on surfaces. Ideally, DHMR happens as late as possible to avoid requiring aseptic operations, as it can be considered a high-risk operations. Preparing the cleanroom for aseptic operations Establishing an ISO (International Organization for Standardization) class 5 space to minimize airborne particles. Maintain low bioburden in the cleanroom by using biocidal cleaners. Using multiple biocidal techniques decreases the likelihood of selecting for resistant microorganisms. 70% Isopropyl Alcohol (IPA) denatures the proteins in a microorganism (note: 70% IPA is better at killing microorganisms than 100% IPA) 7% hydrogen peroxide: damages DNA and proteins through oxygen radical damage. Ultraviolet-C (UV-C) lamps: causes crosslinking in DNA which prevents replication. Monitor cleanroom regularly for bioburden trending: Standard bioassay: Swab or wipe samples of cleanroom surfaces processed for colony forming unity (viable or spore selected); Rapid bioassay: Adenosine triphosphate (ATP) or Limulus amebocyte lysate (LAL) for a bioburden snapshot. High levels can signal an immediate re-cleaning before standard bioassay samples are taken. Airborne monitoring: Active (pulling air through a filter) or passive (particle fallout) for bioburden. Verify bioburden levels just before aseptic operation. Test hardware and cleanroom surfaces and air 3 days before the planned aseptic operation. Rapid bioburden just before aseptic operation to ensure room was not re-contaminated. Preparing personnel and tools: Personnel training. Everyone in the cleanroom: Standard cleanroom certification Everyone on the team: 1 day Planetary Protection overview. Aseptic operators only: Half-day aseptic operations training. Covers sterile garmenting/gloves, Sterile handling with a focus on contact transfer risk, tool/GSE preparation, and two-operator system for opening sterilized tools/components. Tool sterilization: All tools to be used during an aseptic operation need to be identified. Compatible tools are sterilized by DHMR or Autoclave. Double wrapped so that the exterior bag can be handled by a non-sterile operator, and the sterile. Tools that are not compatible with high heat do not come in contact with sensitive surfaces: either substitutes are found, or tools are isolated by wrapping in sterile foil. During an aseptic operation. Pre-task to make sure everyone understands the operations, who is handling what, and when the most critical surfaces will be exposed. Monitoring during the operation. Bioburden: active and passive airborne bioburden sampling, glove-tip dabs onto a plate after completion of operation (3 days for results). Particles: real time particle counter constantly running, with alarm for exceeding ISO 5 conditions.

aseptic processing↗

Satellite Conjunction Assessment Risk Analysis for "Dilution Region" Events: Issues and Operational Approaches

An important activity within Space Traffic Management is the detection and prevention of possible on-orbit collisions between space objects. The principal parameter for assessing collision likelihood is the probability of collision, which is widely accepted among conjunction assessment practitioners; but it possesses a known deficiency in that it can produce a false sense of safety when the orbital position uncertainties for the conjuncting objects are high. The probability of collision is said to be “diluted” in such a situation and to understate the possible risk; certain approaches have been recommended by researchers to provide (largely conservative) risk estimates and remediation methodologies in these cases. The present analysis explores two of the main proposals for quantifying and remediating possible risk in the dilution region and quantifies their operational implications. These implications with regard to imputed additional workload are considerable, especially in anticipating the conjunction event levels expected with the deployment of the USAF Space Fence radar. This effort has been undertaken as part of a larger enterprise that seeks to clarify the philosophical and statistical underpinnings of the conjunction risk assessment process. The analysis presented herein argues that a form of hypothesis testing is implicitly used in conjunction assessment risk analysis, and that there are a number of conceptual and practical reasons for constructing the associated null hypothesis to counsel against a satellite conjunction remediation action. In short, it is concluded that, for the purposes of determining whether a conjunction remediation action should be pursued, dilution-region probabilities of collision should be treated no differently from those produced under other circumstances.

Probability of collision↗