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Aerospace medical and bioengineering considerations in M-2 lifting body research vehicle, discussing protective equipment, escape and medical monitoring systems
For more than 40 years the Los Alamos Neutron Science Center (LANSCE) has provided the scientific underpinnings in nuclear physics and material science needed to ensure the safety and surety of the nuclear stockpile into the future. In addition to national security research, the LANSCE User Facility has a vibrant research program in fundamental science, providing the scientific community with intense sources of neutrons and protons to perform experiments supporting civilian research and the production of medical and research isotopes.
Now, more than ever before, NASA is realizing the value and importance of their intellectual assets. Principles of knowledge management-the systematic use and reuse of information, experience, and expertise to achieve a specific goal-are being applied throughout the agency. LSDA is also applying these solutions, which rely on a combination of content and collaboration technologies, to enable research teams to create, capture, share, and harness knowledge to do the things they do well, even better. In the early days of spaceflight, space life sciences data were collected and stored in numerous databases, formats, media-types and geographical locations. These data were largely unknown/unavailable to the research community. The Biomedical Informatics and Health Care Systems Branch of the Space Life Sciences Directorate at JSC and the Data Archive Project at ARC, with funding from the Human Research Program through the Exploration Medical Capability Element, are fulfilling these requirements through the systematic population of the Life Sciences Data Archive. This project constitutes a formal system for the acquisition, archival and distribution of data for HRP-related experiments and investigations. The general goal of the archive is to acquire, preserve, and distribute these data and be responsive to inquiries for the science communities. Information about experiments and data, as well as non-attributable human data and data from other species' are available on our public Web site http://lsda.jsc.nasa.gov. The Web site also includes a repository for biospecimens, and a utilization process. NASA has undertaken an initiative to develop a Shuttle Data Archive repository. The Shuttle program is nearing its end in 2010 and it is critical that the medical and research data related to the Shuttle program be captured, retained, and usable for research, lessons learned, and future mission planning. Communities of practice are groups of people who share a concern or a passion for something they do, and learn how to do it better as they interact regularly. LSDA works with the HRP community of practice to ensure that we are preserving the relevant research and data they need in the LSDA repository. An evidence-based approach to risk management is required in space life sciences. Evidence changes over time. LSDA has a pilot project with Collexis, a new type of Web-based search engine. Collexis differentiates itself from full-text search engines by making use of thesauri for information retrieval. The high-quality search is based on semantics that have been defined in a life sciences ontology. Additionally, Collexis' matching technology is unique, allowing discovery of partially matching dicuments. Users do not have to construct a complicated (Boolean) search query, but can simply enter a free text search without the risk of getting "no results". Collexis may address these issues by virtue of its retrieval and discovery capabilities across multiple repositories.
Healing of traumatic wounds is complicated by infecting pathogens, with Pseudomonas aeruginosa and members of the Acinetobacter calcoaceticus-baumannii complex among the most common infectious agents. However, a full understanding of genotypic and phenotypic differences between circulating wound isolates is lacking. To address this, traumatic wounds were sampled at Emory University Hospital, and 24 isolates were characterized; we focused on P. aeruginosa and Acinetobacter due to their prevalence and tendency for antibiotic resistance. Even though these species are renowned for antibiotic resistance, only two of the tested isolates could be classified as multidrug resistant. Whole-genome sequencing and analysis revealed that isolates from different patients were genetically distinct; however, longitudinal isolates from the same patient were closely related and appeared to represent chronic colonization by the same strain. Phylogenetic analysis revealed that laboratory strains (PAO1 and AB5075) that were isolated decades previously and from different locations grouped closely to subsets of the recent wound isolates. Given the importance of biofilm formation in infection, the ability of the isolates to form biofilms was assessed; all isolates formed biofilms but showed temporal and magnitude differences. Analysis of a subset of isolates revealed that planktonic P. aeruginosa was resistant to human serum-mediated killing. While the same was true for the majority of Acinetobacter isolates, one showed planktonic sensitivity that was abrogated when grown in a biofilm. Taken together, these data reveal genotypic and phenotypic differences in circulating isolates of P. aeruginosa and A. baumannii.
As NASA transitions its focus to travel back to the moon and on to new destinations, the need to ensure the capture, analysis, and application of research and medical data is of greater urgency than at any other previous time. In this era of limited resources and challenging schedules, the Human Research Program (HRP), based at NASA’s Johnson Space Center (JSC), recognizes the need to extract the greatest possible amount of information from the data already captured. To this end, the HRP Chief Scientist Office (CSO), HRP Program Planning and Control (PP&C) Office, and the Space Medicine Operations Division have been working together to make reuse of both research data and medical monitoring data more accessible to the user community through the Life Science Data Archive (LSDA) and the Lifetime Surveillance of Astronaut Health (LSAH) Repositories. The task of both LSDA and LSAH repositories is to acquire, preserve, and distribute retrospective research (LSDA) and medical (LSAH) data and information both within the NASA community and to the science community at large, for knowledge discovery, retrospective analysis, and planning of future research studies. An additional goal is to encourage collaboration with non-NASA institutions also faced with enhancing human performance in extreme environments. In September 2022, the LSDA website and its contents transitioned to a new NASA Life Sciences Portal (https://nlsp.nasa.gov/explore/lsdahome). This site continues to feature publicly releasable information such as non-attributable datasets, experiment descriptions (from Project Mercury to ISS, as well as from multiple flight analog missions), descriptions of medical monitoring data, and LSAH newsletters (1992 - 2022). The website also provides an updated portal to request additional research and medical data not accessible from the public website. This presentation will provide an in-depth look at the new system as it relates to finding and requesting retrospective data. We will also detail processes from making a request to delivering data for different types of data requests (i.e., attributable, or non-attributable). This includes descriptions of various approval boards, what information and actions the requestor is responsible for, and key milestones in making data available for reuse.
Ebola virus (EBOV) is the causative agent of Ebola disease (EBOD), a viral hemorrhagic fever with a notably high case fatality rate. Current treatments for EBOD are limited to monoclonal antibodies or two licensed viral vector vaccines, a recombinant vesicular stomatitis virus (rVSV)-vectored vaccine or an adenovirus and modified vaccinia Ankara regimen. However, comparisons of protection, efficacy, and durability with alternative nucleotide platforms remain understudied. Here, we evaluated the immunogenicity of an mRNA vaccine expressing the EBOV glycoprotein (GP) in parallel with rVSV- and DNA-based vaccine platforms. The mRNA EBOV-GP vaccine, formulated in lipid nanoparticles, elicited significantly higher levels of total IgG and neutralizing antibody titers compared to the rVSV-EBOV-GP vaccine. Linear antibody epitope analysis indicated a preference for targeting the mucin-like domain in EBOV-GP1 following rVSV-based vaccination, while the mRNA platform distinctly targeted the internal fusion loop of EBOV-GP2. After characterizing the immunogenicity of the mRNA vaccine, two models of EBOD were used to demonstrate its protective efficacy: a surrogate rVSV-based challenge model of EBOD using type-I interferon deficient C57BL/6 mice and infection of BALB/c mice with authentic mouse-adapted EBOV. In both studies, the EBOV mRNA vaccine fully protected the mouse cohorts against morbidity and mortality. Additionally, the EBOV mRNA vaccine produced greater neutralizing antibody titers compared to the DNA EBOV-GP vaccine. These results suggest that an mRNA vaccine expressing EBOV-GP can induce robust, functional humoral responses that are protective against EBOD, warranting further development as an alternative to, or as part of a vaccine strategy including, viral vectored vaccines.
The NASA Johnson Space Center s (NASA JSC) Committee for the Protection of Human Subjects (CPHS) recently approved the formation of two human data repositories: the Lifetime Surveillance of Astronaut Health Repository (LSAH-R) for clinical data and the Life Sciences Data Archive Repository (LSDA-R) for research data. The establishment of these repositories forms the foundation for the release of data and information beyond the scope for which the data was originally collected. The release of clinical and research data and information is primarily managed by two NASA groups: the Evidence Base Working Group (EBWG), consisting of members of both repositories, and the LSAH Policy Board. The goal of unifying these repositories and their processes is to provide a mutually supportive approach to handling medical and research data, to enhance the use of medical and research data to reduce risk, and to promote the understanding of space physiology, countermeasures and other mitigation strategies. Over the past year, both repositories have received over 100 data and information requests from a wide variety of requesters. The disposition of these requests has highlighted the challenges faced when attempting to make data collected on a unique set of subjects available beyond the original intent for which the data were collected. As the EBWG works through each request, many considerations must be factored into account when deciding what data can be shared and how - from the Privacy Act of 1974 and the Health Insurance Portability and Accountability Act (HIPAA), to NASA s Health Information Management System (10HIMS) and Human Experimental and Research Data Records (10HERD) access requirements. Additional considerations include the presence of the data in the repositories and vetting requesters for legitimacy of their use of the data. Additionally, fair access must be ensured for intramural, as well as extramural investigators. All of this must be considered in the formulation of the charters, policies and workflows for the human data repositories at NASA.
The current health maintenance program for ISS is adequate; however the future of medical care and research in space requires a change where crew time efficiency and autonomy are emphasized. NASA s medical personnel are currently refining their ability to monitor and provide remote health care in such a manner. The proposed plan would evaluate health and fitness of the on orbit crew to; perform on orbit operations, and readiness to return to a terrestrial environment. A two tiered approach will utilize exercise and medical equipment, as well as periodic medical conferences with the flight surgeon, to provide a quantitative and clinical picture of the crew s health and fitness. Any off nominal health and fitness issues that could arise will be evaluated by providing an "armamentarium" of devices both medical and exercise specific to the on orbit crew to use. The ability for the crew to provide autonomous health care, with decreasing earth support, will become increasingly more important for exploration missions. This new plan of health care and maintenance will allow us to, development such efforts while continuing to monitor and provide the best possible health, care and medical research through the microgravity environment on board ISS.
Mathematical models have been used for about 30 years to improve our understanding of virus-host interaction, in particular during chronic infections. During the COVID-19 pandemic, these models have been used to provide insights into the natural history of acute SARS-CoV-2 infection, optimize antiviral treatment strategies, understand factors associated with transmission, and optimize surveillance systems. The impact of modeling has been accelerated by the availability of unprecedented multidimensional immune data from animal and human systems, which enhanced partnerships between experimentalists and theorists and led to exciting new modeling and statistical developments. In this mini review, we examine the lessons learned from the COVID-19 pandemic and discuss the main insights provided by mathematical models of viral dynamics at the different stages of the outbreak. Although we focus on respiratory infection, we also consider the new areas for development in anticipation of future acute infections from new or reemerging pathogens.
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Life support system recommendations, and human reaction to medical experiments for orbital research laboratory
Magnetic nanoparticles have proven invaluable for biomechanical investigations due to their ability to exert localized forces. However, cellular delivery of exogenous magnetic agents often results in endosomal entrapment, thereby limiting their utility for manipulating subcellular structures. This study characterizes and exploits fully genetically controlled biomineralization of iron-oxide cores inside encapsulin nanocompartments to enable magnetic-activated cell sorting (MACS) and magnetic cell manipulation. The fraction of MACS-retained cells showed substantial overexpression of encapsulins and exhibited both para- and ferrimagnetic responses with magnetic moments of 10 -15 A m 2 per cell, comparable to standard exogenous labels for MACS. Electron microscopy revealed that MACS-retained cells contained densely packed agglomerates of ≈30 nm iron oxide cores consisting of ultrafine quasicrystalline ordered nuclei within an amorphous matrix of iron, oxygen, and phosphorus. Scanning transmission X-ray microscopy, X-ray absorption spectroscopy, and Raman microspectroscopy confirmed that the iron-oxide species are consistent with ferric oxide (Fe 2 O 3 ). In addition, the encapsulin-overexpressing MACS-retained cells can be manipulated by a magnetic needle and regrown in patterns determined by magnetic gradients. This study demonstrates that the formation of quasicrystalline iron oxide with mixed para/ferrimagnetic behavior in the cytosol of mammalian cells enables magnetic manipulation without the delivery of exogenous agents.
The SRP believes strongly that regularly performed in-flight crew assessments are needed in order to identify a change in health status before a medical condition becomes clinically apparent. It is this early recognition in change that constitutes the foundation of the "occupational health model" expounded in the HRP Requirements Document as a key component of the HRP risk mitigation strategy that will enable its objective of "prevention and mitigation of human health and performance risks". A regular crew status examination of physiological and clinical performance is needed. This can be accomplished through instrumented monitoring of routine embedded tasks. The SRP recommends addition of a new gap to address this action under Category 3.0 Mitigate the Risk. This new gap is closely associated with Task 4.19 which addresses the lack of adequate biomedical monitoring capabilities for performing periodic clinical status evaluations and contingency medical monitoring. A corollary to these gaps is the critical emphasis on preventive medicine, not only during pre- and post-flight phases of a mission as is the current practice, but continued into the in-flight phases of exploration class missions.
ABSTRACT Aims Humans and animals acutely intoxicated with the organophosphate soman can develop sustained status epilepticus (SE) that rapidly becomes refractory to benzodiazepines. We compared the antiseizure efficacy of midazolam, a current standard of care treatment for OP‐induced SE, versus combined therapy with midazolam and allopregnanolone (ALLO) in a rat model of soman‐induced SE. Methods Soman‐intoxicated male rats with robust seizure behavior and high‐amplitude electroencephalographic (EEG) activity were administered midazolam (0.65 mg, i.m.) 20 min after seizure initiation and 10 min later either a second dose of midazolam or ALLO (12 or 24 mg/kg, i.m.). Seizure behavior and EEG were monitored for 4 h after treatment. Brains were collected at the end of the monitoring period for histological analyses. Results Animals receiving 2 doses of midazolam exhibited persistent SE. Sequential dosing with midazolam followed by ALLO suppressed electrographic seizure activity. The combination therapy also significantly reduced soman‐induced neurodegeneration and neuroinflammation compared to 2 doses of midazolam. High but not low dose ALLO was associated with transitory and reversible respiratory compromise during the 1 h period after dosing. Conclusions Treatment with midazolam followed by ALLO was more effective than 2 doses of midazolam in suppressing benzodiazepine‐refractory, soman‐induced SE, and in mitigating its acute neuropathological consequences.
Medical cybersecurity research addresses the critical intersection of healthcare and digital security. As medical devices expand and become increasingly interconnected, the healthcare sector is poised to become a primary target for cyber warfare. This project aims to mitigate the risks associated with a field that often underestimates the importance of cybersecurity.
This report presents the findings from market research conducted for NASA’s Aerial Aid Convergent Aeronautics Solutions (CAS) exploration project, which aims to assess the current state of the market and technological readiness for Uncrewed Aerial Systems (UAS) for medical emergency first response. The research reveals a robust and rapidly growing market for UAS, with a notable emerging sector for Drones as First Responders (DFR). Despite this growth, DFR applications are currently limited by regulatory, technical, and other challenges, which restrict their use primarily to manned remote video surveillance, and therefore are primarily employed by police units. To our knowledge, there is no evidence of UAS being utilized by medical first responders for scene assessment. Limited evidence exists for closely related applications; however, these are mostly confined to pilot programs for the delivery of medical supplies or equipment. Although there has been discussion around fully autonomous DFR applications for medical purposes such as UAS ambulances or patient transport drones, these applications are generally not yet operational in practice. The technology for full autonomy, especially in guidance and control, has seen significant advancements, and recent Federal Aviation Administration (FAA)regulations are likely to accelerate adoption. Computer vision algorithms for fully autonomous medical emergency response scene surveillance are primed for advancement and deployment. A notable gap likely exists between advancements in computer vision research and what is being integrated in the commercial DFR sector. This gap is primarily due to challenges such as quality assurance for autonomous systems, the availability of application-specific training datasets for computer vision algorithms, regulatory constraints, and public perception and privacy concerns.
On 26th October 2023, ExMC convened a panel of Subject Matter Experts (SMEs) from NASA, broadly representing Headquarters, the Human Research Program, Medical Operations, the Human Health and Performance Directorate at JSC, the Health and Medical Technical Authority, the Flight Operations Directorate, and representation from other Centers including: Ames Research Center (ARC), and Glenn Research Center (GRC). Representatives from the Canadian Space Agency also participated in this TIM. In addition, SMEs from industry included representation from the following entities: Axiom Space, Space Exploration Technologies Corporation, Level Ex, Shiny Box Interactive. Additional SMEs from academia included: University of Houston, Touro University, Weill Cornell Medical College and the Translational Research Institute for Space Health at Baylor College of Medicine. This group of stakeholders discussed the training issues related to facilitating EIMO. Sub-topics for this discussion included the following: - Pre-launch medical curriculum development - Ground-based training on medical hardware - Dental health - Behavioral health - Telemedicine - Just-in-time training - Simulation-based training (extended reality)
Proton and light-ion accelerators have many research and medical applications, but the current state of technology in accelerators severely limits their widespread use: (1) synchrotrons have an intrinsic low duty cycle and become quite large for light ions; and (2) cyclotrons do not have energy variability and require complex superconducting magnets for high energy. A new concept in non-scaling Fixed-Field Alternating-Gradient (FFAGs) has been invented that incorporates both the energy variability of the synchrotron and the high duty cycle of the cyclotron. The concept uses normal-conducting, combined-function magnets that apply only constant (dipole) and linear-gradient (quadrupole) fields to stabilize the accelerator. This project will develop an optimized design for a new non-scaling and cost-effective innovation in FFAG accelerators. The accelerator design will have optics that can stably accelerate protons to 250 MeV (or higher) and carbon ions to =200 MeV, an energy considered ideal for radiation therapy. Phase I will optimize, fully simulate, and demonstrate the feasibility of this accelerator. Commercial Applications and other Benefits as described by the awardee: The fixed-field acceleration concept should eliminate some of the most pronounced technical difficulties, expense, maintenance, and required expertise faced in conventional proton and light-ion accelerators. In addition to the application for high energy physics, these accelerators should have application in cancer treatment, radiopharmaceuticals, and medical isotope production, and materials science.