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At least 73 records · Page 4

Capacity of wild-type and chemokine-armed parvovirus H-1PV for inhibiting neo-angiogenesis

Anti-angiogenic therapy has been recognized as a powerful potential strategy for impeding the growth of various tumors. However no major therapeutic effects have been observed to date, mainly because of the emergence of several resistance mechanisms. Among novel strategies to target tumor vasculature, some oncolytic viruses open up new prospects. In this context, we addressed the question whether the rodent parvovirus H-1PV can target endothelial cells. We show that cultures of human normal (HUVEC) and immortalized (KS-IMM) endothelial cells sustain an abortive viral cycle upon infection with H-1PV and are sensitive to H-1PV cytotoxicity. H-1PV significantly inhibits infected KS-IMM tumor growth. This effect may be traced back by the virus ability to both kill proliferating endothelial cells and inhibit VEGF production Recombinant H-1PV vectors can also transduce tumor cells with chemokines endowed with anti-angiogenesis properties, and warrant further validation for the treatment of highly vascularized tumors. - Highlights: • The oncolytic parvovirus H-1PV can target endothelial cells. • Abortive viral cycle upon infection of endothelial cells with H-1PV. • Inhibition of VEGF expression and KS-IMM tumor growth by H-1PV.

60 APPLIED LIFE SCIENCES↗

Investigation of Off-Stoichiometry in Ternary Nitrides by EDS and HRTEM

We demonstrate an inverted metamorphic multijunction (IMM) photovoltaic cell comprising lattice-mismatched 1.2 eV AlGaInAs and 1.0 eV GaInAs junctions optimized for high-temperature thermophotovoltaic (TPV) applications. This device differs from traditional IMM solar cells because the mismatched junctions are grown at a single lattice constant. This architecture enables removal of the compositionally graded buffer which otherwise filters light from the junctions below and absorbs sub-bandgap light via free-carrier absorption. Sub-bandgap absorption dramatically reduces the efficiency of TPV systems using high reflectivity cells to enable bandedge spectrum filtering. Three components required development to enable this device: 1) a lattice-mismatched 1.2 eV AlGaInAs junction, 2) a metamorphic contact layer grown after the graded buffer, and 3) a transparent tunnel junction that sits in front of the 1.0 eV GaInAs junction. Growth conditions that minimize oxygen defect incorporation maximize AlGaInAs cell quality, enabling a 0.41 V bandgap open circuit voltage offset at 22 mA/cm2 under AM1.5D. A mismatched GaInAs:Se layer is developed as a low resistance contact. Lastly we develop a GaAsSb:C/GaInP:Se tunnel junction suitable for high-power densities with more transparency than the GaAsSb:C/GaInP:Se structure used in past IMM cells. We characterize the tandem device under a high-intensity spectrum that approximates the emission from a 2150 °C blackbody radiator and deduce a projected ideal TPV efficiency of 39.9% at ~30% of the blackbody irradiance, and 36% ideal TPV efficiency under the full 118 W/cm2 irradiance. Improvements to the back-surface reflectivity and series resistance are expected to increase the ideal TPV efficiency well above 40%.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Long-term super-resolution inner mitochondrial membrane imaging with a lipid probe

The inner mitochondrial membrane (IMM) generates power to drive cell function, and its dynamics control mitochondrial health and cellular homeostasis. Here, we describe the cell-permeant, lipid-like small molecule MAO-N 3 and use it to assemble high-density environmentally sensitive (HIDE) probes that selectively label and image the IMM in live cells and multiple cell states. MAO-N 3 pairs with strain-promoted azide–alkyne click chemistry-reactive fluorophores to support HIDE imaging using confocal, structured illumination, single-molecule localization and stimulated emission depletion microscopy, all with significantly improved resistance to photobleaching. These probes generate images with excellent spatial and temporal resolution, require no genetic manipulations, are non-toxic in model cell lines and primary cardiomyocytes (even under conditions that amplify the effects of mitochondrial toxins) and can visualize mitochondrial dynamics for 12.5 h. This probe will enable comprehensive studies of IMM dynamics with high temporal and spatial resolution.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Six-Junction Concentrator Solar Cells

We report on six-junction inverted metamorphic (6J IMM) solar cells developed for concentrator applications. Monolithic III-V structures are grown by metal organic vapor phase epitaxy with junction bandgaps of 2.06, 1.70, 1.40, 1.16, 0.94, and 0.70 eV. The top three junctions are lattice-matched to the GaAs substrate, but the bottom three junctions use three consecutive metamorphic compositionally graded buffers to transition the lattice constant to GaxIn1-xAs compositions with the previously listed bandgaps. Performance of 6J IMM devices at one-sun AM1.5 Direct conditions gives VOC = 5.301 V, JSC = 8.05 mA/cm2, fill factor=83.9%, and efficiency=35.8%. Promising operation at high concentration is achieved but the spectrum was not controlled to AM1.5D. Tunnel junctions do not limit until at least several hundred suns. High concentration performance appears to be limited by internal heterojunction barriers created by zinc diffusion that decreases the fill factor. The properties of each junction within the 6J IMM have been separately characterized through electroluminescence and luminescent coupling measurements.

14 SOLAR ENERGY↗

Inverted Metamorphic AlGaInAs/GaInAs Tandem Thermophotovoltaic Cell Designed for Thermal Energy Grid Storage Application

We demonstrate an inverted metamorphic multijunction (IMM) photovoltaic cell comprising lattice-mismatched 1.2 eV AlGaInAs and 1.0 eV GaInAs junctions optimized for high-temperature thermophotovoltaic (TPV) applications. This device differs from traditional IMM solar cells because the mismatched junctions are grown at a single lattice constant. This architecture enables removal of the compositionally graded buffer that otherwise filters light from the junctions below and absorbs sub-bandgap light via free-carrier absorption. Sub-bandgap absorption dramatically reduces the efficiency of TPV systems using high reflectivity cells to enable band edge spectrum filtering. Three components required development to enable this device: (1) a lattice-mismatched 1.2 eV AlGaInAs junction, (2) a metamorphic contact layer grown after the graded buffer, and (3) a transparent tunnel junction that sits in front of the 1.0 eV GaInAs junction. Growth conditions that minimize oxygen defect incorporation maximize AlGaInAs cell quality, enabling a 0.41 V bandgap open circuit voltage offset at 22 mA/cm2 under AM1.5D. A mismatched GaInAs:Se layer is developed as a low resistance contact. Lastly, we develop a GaAsSb:C/GaInP:Se tunnel junction suitable for high-power densities with more transparency than the GaAsSb:C/GaInAs:Se structure used in past IMM cells. We characterize the tandem device under a high-intensity spectrum that approximates the emission from a 2150°C blackbody radiator and deduce a projected ideal TPV efficiency of 39.9% at ~30% of the blackbody irradiance and 36% ideal TPV efficiency under the full 118 W/cm2 irradiance. Improvements to the back-surface reflectivity and series resistance are expected to increase the ideal TPV efficiency well above 40%.

25 ENERGY STORAGE↗

Mass measurement of 27 P to constrain type-I x-ray burst models and validate the isobaric multiplet mass equation for the $A = 27, T = \frac{3}{2}$ isospin quartet

Background: Light curves are the primary observable of type-I x-ray bursts. Computational x-ray burst models must match simulations to observed light curves. Most of the error in simulated curves comes from uncertainties in rp process reaction rates, which can be reduced via precision mass measurements of neutron-deficient isotopes in the rp process path. Purpose: Perform a precise atomic mass measurement of 27 P. Use this new measurement to calculate rp process reaction rates and input these rates into an x-ray burst model to reduce simulated light curve uncertainty. Use the mass measurement of 27 P to validate the isobaric multiplet mass equation (IMME) for the A = 27 T = 3/2 isospin quartet which 27 P belongs to. Method: High-precision Penning trap mass spectrometry utilizing the time-of-flight ion cyclotron resonance technique was used to determine the atomic mass of 27 P. The MESA code (Modules for Experiments in Stellar Astrophysics) was then used to simulate x-ray bursts using a one-dimensional multizone model to produce updated light curves. Results: The mass excess of 27 P was measured to be –670.7(6) keV, a 14-fold precision increase over the mass reported in the 2020 Atomic Mass Evaluation (AME2020). The 26 Si(p, $γ$) 27 P– 27 P($γ$, p) 26 Si rate equilibrium has been determined to a higher precision based on the precision mass measurement of 27 P. x-ray burst light curves were produced with the MESA code using the new reaction rates. Changes in the mass of 27 P seem to have minimal effect on light curves, even in burster systems tailored to maximize impact. Conclusion: The mass of 27 P does not play a significant role in x-ray burst light curves. It is important to understand that more advanced models do not just provide more precise results, but often qualitatively different ones. This result brings us a step closer to being able to extract stellar parameters from individual x-ray burst observations. In addition, the IMME has been validated for the A = 27, T = 3/2 quartet. The normal quadratic form of the IMME using the latest data yields a reduced $χ$ 2 of 2.9. Finally, the cubic term required to generate an exact fit to the latest data matches theoretical attempts to predict this term.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗

Building a Six-Junction Inverted Metamorphic Concentrator Solar Cell

We propose practical six-junction (6J) inverted metamorphic multijunction (IMM) concentrator solar cell designs with the potential to exceed 50% efficiency using moderately high quality junction materials. We demonstrate the top three junctions and their monolithic integration lattice matched to GaAs using 2.1-eV AlGaInP, 1.7-eV AlGaAs or GaInAsP, and 1.4-eV GaAs with external radiative efficiencies >0.1%. We demonstrate tunnel junctions with peak tunneling current >400 A/cm 2 that are transparent to <2.1-eV light. We compare the bottom three GaInAs(p) junctions with bandgaps of 1.2, 1.0, and 0.7 eV grown on InP and transparent metamorphic grades with low dislocation densities. The solution to an integration challenge resulting from Zn diffusion in the GaAs junction is illustrated in a five-junction IMM. Excellent 1-sun performance is demonstrated in a complete 6J IMM device with VOC = 5.15 V, and a promising pathway toward >50% efficiency at high concentrations is presented.

14 SOLAR ENERGY↗

Development of a High Volume Capable Process to Manufacture High Performance Photovoltaic Cells

The intent of the work is for RFMD and NREL to cooperate in the development of a commercially viable and high volume capable process to manufacture high performance photovoltaic cells, based on inverted metamorphic (IMM) GaAs technology. The successful execution of the agreement will result in the production of a PV cell using technology that is capable of conversion efficiency at par with the market at the time of release (reference 2009: 37-38%), using RFMD's production facilities. The CRADA work has been divided into three phases: (1) a foundation phase where the teams will demonstrate the manufacturing of a basic PV cell at RFMD's production facilities; (2) a technology demonstration phase where the teams will demonstrate the manufacturing of prototype PV cells using IMM technology at RFMD's production facilities, and; (3) a production readiness phase where the teams will demonstrate the capability to manufacture PV cells using IMM technology with high yields, high reliability, high reproducibility and low cost.

14 SOLAR ENERGY↗

A mission design for International Manned Mars Mission - From the 1991 International Space University (ISU) Design Project

The International Space University (ISU) conducted a study of an international program to support human exploration of Mars as its annual Design Project activity during its 1991 summer session in Toulouse, France. Although an ISU Design Project strives to produce an in-depth analysis during the intense 10-week summer session, the International Mars Mission (IMM) project was conducted in a manner designed to provide a learning experience for young professionals working in an unusual multidisciplinary and multinational environment. The breadth of the IMM study exceeds that of most Mars mission studies of the past, encompassing political organization for long-term commitment, multinational management structure, cost analysis, mission architecture, vehicle configuration, crew health, life support, Mars surface infrastructure, mission operations, technology evaluation, risk assessment, scientific planning, exploration, communication networks, and Martian resource utilization. The IMM Final Report has particular value for those seeking insight into the choices made by a multinational group working in an apolitical environment on the problems of international cooperation in space.

Mendell, Wendell W.↗

Generation and Radiation of Acoustic Waves from a 2-D Shear Layer

A parallel numerical simulation of the radiation of sound from an acoustic source inside a 2-D jet is presented in this paper. This basic benchmark problem is used as a test case for scattering problems that are presently being solved by using the Impedance Mismatch Method (IMM). In this technique, a solid body in the domain is represented by setting the acoustic impedance of each medium, encountered by a wave, to a different value. This impedance discrepancy results in reflected and scattered waves with appropriate amplitudes. The great advantage of the use of this method is that no modifications to a simple Cartesian grid need to be made for complicated geometry bodies. Thus, high order finite difference schemes may be applied simply to all parts of the domain. In the IMM, the total perturbation field is split into incident and scattered fields. The incident pressure is assumed to be known and the equivalent sources for the scattered field are associated with the presence of the scattering body (through the impedance mismatch) and the propagation of the incident field through a non-uniform flow. An earlier version of the technique could only handle uniform flow in the vicinity of the source and at the outflow boundary. Scattering problems in non-uniform mean flow are of great practical importance (for example, scattering from a high lift device in a non-uniform mean flow or the effects of a fuselage boundary layer). The solution to this benchmark problem, which has an acoustic wave propagating through a non-uniform mean flow, serves as a test case for the extensions of the IMM technique.

Agarwal, Anurag↗

A Bayesian approach to tracking patients having changing pharmacokinetic parameters

This paper considers the updating of Bayesian posterior densities for pharmacokinetic models associated with patients having changing parameter values. For estimation purposes it is proposed to use the Interacting Multiple Model (IMM) estimation algorithm, which is currently a popular algorithm in the aerospace community for tracking maneuvering targets. The IMM algorithm is described, and compared to the multiple model (MM) and Maximum A-Posteriori (MAP) Bayesian estimation methods, which are presently used for posterior updating when pharmacokinetic parameters do not change. Both the MM and MAP Bayesian estimation methods are used in their sequential forms, to facilitate tracking of changing parameters. Results indicate that the IMM algorithm is well suited for tracking time-varying pharmacokinetic parameters in acutely ill and unstable patients, incurring only about half of the integrated error compared to the sequential MM and MAP methods on the same example.

Bayes Theorem↗

Assessment of Medical Risks and Optimization of their Management using Integrated Medical Model

The Integrated Medical Model (IMM) Project is a software-based technique that will identify and quantify the medical needs and health risks of exploration crew members during space flight and evaluate the effectiveness of potential mitigation strategies. The IMM Project employs an evidence-based approach that will quantify probability and consequences of defined in-flight medical risks, mitigation strategies, and tactics to optimize crew member health. Using stochastic techniques, the IMM will ultimately inform decision makers at both programmatic and institutional levels and will enable objective assessment of crew health and optimization of mission success using data from relevant cohort populations and from the astronaut population. The objectives of the project include: 1) identification and documentation of conditions that may occur during exploration missions (Baseline Medical Conditions List [BMCL), 2) assessment of the likelihood of conditions in the BMCL occurring during exploration missions (incidence rate), 3) determination of the risk associated with these conditions and quantify in terms of end states (Loss of Crew, Loss of Mission, Evacuation), 4) optimization of in-flight hardware mass, volume, power, bandwidth and cost for a given level of risk or uncertainty, and .. validation of the methodologies used.

Fitts, Mary A.↗

Autonomous, In-Flight Crew Health Risk Management for Exploration-Class Missions: Leveraging the Integrated Medical Model for the Exploration Medical System Demonstration Project

The Integrated Medical Model (IMM) captures organizational knowledge across the space medicine, training, operations, engineering, and research domains. IMM uses this knowledge in the context of a mission and crew profile to forecast risks to crew health and mission success. The IMM establishes a quantified, statistical relationship among medical conditions, risk factors, available medical resources, and crew health and mission outcomes. These relationships may provide an appropriate foundation for developing an in-flight medical decision support tool that helps optimize the use of medical resources and assists in overall crew health management by an autonomous crew with extremely limited interactions with ground support personnel and no chance of resupply.

Butler, D. J.↗

Estimated Probability of a Cervical Spine Injury During an ISS Mission

Introduction: The Integrated Medical Model (IMM) utilizes historical data, cohort data, and external simulations as input factors to provide estimates of crew health, resource utilization and mission outcomes. The Cervical Spine Injury Module (CSIM) is an external simulation designed to provide the IMM with parameter estimates for 1) a probability distribution function (PDF) of the incidence rate, 2) the mean incidence rate, and 3) the standard deviation associated with the mean resulting from injury/trauma of the neck. Methods: An injury mechanism based on an idealized low-velocity blunt impact to the superior posterior thorax of an ISS crewmember was used as the simulated mission environment. As a result of this impact, the cervical spine is inertially loaded from the mass of the head producing an extension-flexion motion deforming the soft tissues of the neck. A multibody biomechanical model was developed to estimate the kinematic and dynamic response of the head-neck system from a prescribed acceleration profile. Logistic regression was performed on a dataset containing AIS1 soft tissue neck injuries from rear-end automobile collisions with published Neck Injury Criterion values producing an injury transfer function (ITF). An injury event scenario (IES) was constructed such that crew 1 is moving through a primary or standard translation path transferring large volume equipment impacting stationary crew 2. The incidence rate for this IES was estimated from in-flight data and used to calculate the probability of occurrence. The uncertainty in the model input factors were estimated from representative datasets and expressed in terms of probability distributions. A Monte Carlo Method utilizing simple random sampling was employed to propagate both aleatory and epistemic uncertain factors. Scatterplots and partial correlation coefficients (PCC) were generated to determine input factor sensitivity. CSIM was developed in the SimMechanics/Simulink environment with a Monte Carlo wrapper (MATLAB) used to integrate the components of the module. Results: The probability of generating an AIS1 soft tissue neck injury from the extension/flexion motion induced by a low-velocity blunt impact to the superior posterior thorax was fitted with a lognormal PDF with mean 0.26409, standard deviation 0.11353, standard error of mean 0.00114, and 95% confidence interval [0.26186, 0.26631]. Combining the probability of an AIS1 injury with the probability of IES occurrence was fitted with a Johnson SI PDF with mean 0.02772, standard deviation 0.02012, standard error of mean 0.00020, and 95% confidence interval [0.02733, 0.02812]. The input factor sensitivity analysis in descending order was IES incidence rate, ITF regression coefficient 1, impactor initial velocity, ITF regression coefficient 2, and all others (equipment mass, crew 1 body mass, crew 2 body mass) insignificant. Verification and Validation (V&V): The IMM V&V, based upon NASA STD 7009, was implemented which included an assessment of the data sets used to build CSIM. The documentation maintained includes source code comments and a technical report. The software code and documentation is under Subversion configuration management. Kinematic validation was performed by comparing the biomechanical model output to established corridors.

Brooker, John E.↗

Probabilistic Modeling of the Renal Stone Formation Module

The Integrated Medical Model (IMM) is a probabilistic tool, used in mission planning decision making and medical systems risk assessments. The IMM project maintains a database of over 80 medical conditions that could occur during a spaceflight, documenting an incidence rate and end case scenarios for each. In some cases, where observational data are insufficient to adequately define the inflight medical risk, the IMM utilizes external probabilistic modules to model and estimate the event likelihoods. One such medical event of interest is an unpassed renal stone. Due to a high salt diet and high concentrations of calcium in the blood (due to bone depletion caused by unloading in the microgravity environment) astronauts are at a considerable elevated risk for developing renal calculi (nephrolithiasis) while in space. Lack of observed incidences of nephrolithiasis has led HRP to initiate the development of the Renal Stone Formation Module (RSFM) to create a probabilistic simulator capable of estimating the likelihood of symptomatic renal stone presentation in astronauts on exploration missions. The model consists of two major parts. The first is the probabilistic component, which utilizes probability distributions to assess the range of urine electrolyte parameters and a multivariate regression to transform estimated crystal density and size distributions to the likelihood of the presentation of nephrolithiasis symptoms. The second is a deterministic physical and chemical model of renal stone growth in the kidney developed by Kassemi et al. The probabilistic component of the renal stone model couples the input probability distributions describing the urine chemistry, astronaut physiology, and system parameters with the physical and chemical outputs and inputs to the deterministic stone growth model. These two parts of the model are necessary to capture the uncertainty in the likelihood estimate. The model will be driven by Monte Carlo simulations, continuously randomly sampling the probability distributions of the electrolyte concentrations and system parameters that are inputs into the deterministic model. The total urine chemistry concentrations are used to determine the urine chemistry activity using the Joint Expert Speciation System (JESS), a biochemistry model. Information used from JESS is then fed into the deterministic growth model. Outputs from JESS and the deterministic model are passed back to the probabilistic model where a multivariate regression is used to assess the likelihood of a stone forming and the likelihood of a stone requiring clinical intervention. The parameters used to determine to quantify these risks include: relative supersaturation (RS) of calcium oxalate, citrate/calcium ratio, crystal number density, total urine volume, pH, magnesium excretion, maximum stone width, and ureteral location. Methods and Validation: The RSFM is designed to perform a Monte Carlo simulation to generate probability distributions of clinically significant renal stones, as well as provide an associated uncertainty in the estimate. Initially, early versions will be used to test integration of the components and assess component validation and verification (V&V), with later versions used to address questions regarding design reference mission scenarios. Once integrated with the deterministic component, the credibility assessment of the integrated model will follow NASA STD 7009 requirements.

kidney stones↗

The Integrated Medical Model: A Probabilistic Simulation Model Predicting In-Flight Medical Risks

The Integrated Medical Model (IMM) is a probabilistic model that uses simulation to predict mission medical risk. Given a specific mission and crew scenario, medical events are simulated using Monte Carlo methodology to provide estimates of resource utilization, probability of evacuation, probability of loss of crew, and the amount of mission time lost due to illness. Mission and crew scenarios are defined by mission length, extravehicular activity (EVA) schedule, and crew characteristics including: sex, coronary artery calcium score, contacts, dental crowns, history of abdominal surgery, and EVA eligibility. The Integrated Medical Evidence Database (iMED) houses the model inputs for one hundred medical conditions using in-flight, analog, and terrestrial medical data. Inputs include incidence, event durations, resource utilization, and crew functional impairment. Severity of conditions is addressed by defining statistical distributions on the dichotomized best and worst-case scenarios for each condition. The outcome distributions for conditions are bounded by the treatment extremes of the fully treated scenario in which all required resources are available and the untreated scenario in which no required resources are available. Upon occurrence of a simulated medical event, treatment availability is assessed, and outcomes are generated depending on the status of the affected crewmember at the time of onset, including any pre-existing functional impairments or ongoing treatment of concurrent conditions. The main IMM outcomes, including probability of evacuation and loss of crew life, time lost due to medical events, and resource utilization, are useful in informing mission planning decisions. To date, the IMM has been used to assess mission-specific risks with and without certain crewmember characteristics, to determine the impact of eliminating certain resources from the mission medical kit, and to design medical kits that maximally benefit crew health while meeting mass and volume constraints.

Risk Analysis↗

Clinical Outcome Metrics for Optimization of Robust Training

Introduction: The emphasis of this research is on the Human Research Program (HRP) Exploration Medical Capability's (ExMC) "Risk of Unacceptable Health and Mission Outcomes Due to Limitations of In-Flight Medical Capabilities." Specifically, this project aims to contribute to the closure of gap ExMC 2.02: We do not know how the inclusion of a physician crew medical officer quantitatively impacts clinical outcomes during exploration missions. The experiments are specifically designed to address clinical outcome differences between physician and non-physician cohorts in both near-term and longer-term (mission impacting) outcomes. Methods: Medical simulations will systematically compare success of individual diagnostic and therapeutic procedure simulations performed by physician and non-physician crew medical officer (CMO) analogs using clearly defined short-term (individual procedure) outcome metrics. In the subsequent step of the project, the procedure simulation outcomes will be used as input to a modified version of the NASA Integrated Medical Model (IMM) to analyze the effect of the outcome (degree of success) of individual procedures (including successful, imperfectly performed, and failed procedures) on overall long-term clinical outcomes and the consequent mission impacts. The procedures to be simulated are endotracheal intubation, fundoscopic examination, kidney/urinary ultrasound, ultrasound-guided intravenous catheter insertion, and a differential diagnosis exercise. Multiple assessment techniques will be used, centered on medical procedure simulation studies occurring at 3, 6, and 12 months after initial training (as depicted in the following flow diagram of the experiment design). Discussion: Analysis of procedure outcomes in the physician and non-physician groups and their subsets (tested at different elapsed times post training) will allow the team to 1) define differences between physician and non-physician CMOs in terms of both procedure performance (pre-IMM analysis) and overall mitigation of the mission medical impact (IMM analysis); 2) refine the procedure outcome and clinical outcome metrics themselves; 3) refine or develop innovative medical training products and solutions to maximize CMO performance; and 4) validate the methods and products of this experiment for operational use in the planning, execution, and quality assurance of the CMO training process The team has finalized training protocols and developed a software training/testing tool in collaboration with Butler Graphics (Detroit, MI). In addition to the "hands on" medical procedure modules, the software includes a differential diagnosis exercise (limited clinical decision support tool) to evaluate the diagnostic skills of participants. Human subject testing will occur over the next year.

Ebert, D.↗

The Integrated Medical Model: A Probabilistic Simulation Model for Predicting In-Flight Medical Risks

The Integrated Medical Model (IMM) is a probabilistic model that uses simulation to predict mission medical risk. Given a specific mission and crew scenario, medical events are simulated using Monte Carlo methodology to provide estimates of resource utilization, probability of evacuation, probability of loss of crew, and the amount of mission time lost due to illness. Mission and crew scenarios are defined by mission length, extravehicular activity (EVA) schedule, and crew characteristics including: sex, coronary artery calcium score, contacts, dental crowns, history of abdominal surgery, and EVA eligibility. The Integrated Medical Evidence Database (iMED) houses the model inputs for one hundred medical conditions using in-flight, analog, and terrestrial medical data. Inputs include incidence, event durations, resource utilization, and crew functional impairment. Severity of conditions is addressed by defining statistical distributions on the dichotomized best and worst-case scenarios for each condition. The outcome distributions for conditions are bounded by the treatment extremes of the fully treated scenario in which all required resources are available and the untreated scenario in which no required resources are available. Upon occurrence of a simulated medical event, treatment availability is assessed, and outcomes are generated depending on the status of the affected crewmember at the time of onset, including any pre-existing functional impairments or ongoing treatment of concurrent conditions. The main IMM outcomes, including probability of evacuation and loss of crew life, time lost due to medical events, and resource utilization, are useful in informing mission planning decisions. To date, the IMM has been used to assess mission-specific risks with and without certain crewmember characteristics, to determine the impact of eliminating certain resources from the mission medical kit, and to design medical kits that maximally benefit crew health while meeting mass and volume constraints.

Risk Analysis↗