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Evaluation of the spaceflight cardiovascular risk using the clinical prediction model Astro-CHARM and the NASA Radiation Risk Model

- Exposure to space radiation may pose a risk for cardiovascular diseases (CVD) during and after spaceflight. - The CVD risk should be quantified to plan future long-duration space missions such as the manned flight to Mars. - Assessing CVD risk is complicated by its multifactorial nature, where an individual’s risk is strongly influenced by risk factors such as family history, blood pressure, and lipid profiles. - In the NASA Space Radiation Risk Model, the metrics of radiation exposure-induced cases (REIC) and radiation exposure-induced death (REID) are used to quantify the risk attributable to radiation over a lifetime after exposure.

Ianik Plante↗

Crew State and Risk Model Development to Predict Hydration Status During Extravehicular Activity Training Events

Introduction: Hydration is critical for optimal human health and performance and dehydration can lead to impaired cardiovascular function, thermal dysregulation, decreased blood plasma volume, and cognitive impacts, particularly during physical activity. Prolonged and repeated extravehicular activities (EVA) without sufficiently available drinking water may increase risk for dehydration, which could impair crew health and impact mission success. Understanding hydration needs and potential effects on health and performance are necessary to optimize crew well-being and enable successful EVA objectives. This study aims to develop a model of hydration status during EVA using water balance techniques. Methods: Water balance measures were collected on 15 healthy astronauts who performed ≈6-hour simulated microgravity extravehicular activity (EVA) training in the NASA Neutral Buoyancy Laboratory (NBL). Data collected included pre-and post-EVA nude body weight (BW), maximum absorption garment (MAG) weight, Disposable In-suit Drink Bag (DIDB) weight, urine specific gravity (USG), and extra pre-EVA intake (W). Variables were combined to create the water balance model as pre-EVA (Hn)= BWn+ MAGn+ DIDBn+ Wnand post EVA (Hn+1) = BWn+1+ MAGn+1+ DIDBn+1. Urine specific gravity values were used to refine water balance measures into hydration categories: Hydrated, Marginally Hydrated, and Dehydrated. Results: Pre-EVA modeling indicated53% of crew were hydrated, 20% were marginally hydrated, and 27% were dehydrated. Alternately, Hn+1 showed 13% of crew remained hydrated, 47% were marginally hydrated, and 40% were dehydrated at the end of the EVA. Furthermore, 75% of the crewmembers who started sufficiently hydrated finished the run marginally hydrated or dehydrated. According to USG indices presented by Casa and Lawrence, et al. (2000), only 25% of the crew started and remained hydrated throughout the EVA, and those who were dehydrated at the outset stayed dehydrated. Conclusion: Model outcomes assessing hydration status during 6-hour simulated microgravity EVAs demonstrate the necessity to further address hydration requirements for optimal human performance during spaceflight and EVA. This study enables additional baseline development of the Crew State and Risk Model Hydration, Nutrition, and Waste Management component that aims to provide individualized crew state and risk predictions during EVAs. Reference: Casa, D. J., Armstrong, L. E., et al. (2000). National Athletic Trainers’ Association Position Statement: Fluid Replacement for Athletes. Journal of Athletic Training, 35:212-224.

L Cooper↗

Designing a Decontamination Solution for the Low-Earth-Orbit, Cryogenic SPHEREx Mission

To address the scientific goals of NASA’s astrophysics division, the JPL and Caltech’s SPHEREx mission conducts the first near-infrared all-sky spectral survey in low-earth-orbit using a passively-cooled, cryogenic telescope. Several unique water contamination issues arise due to the combination of cryogenic operation temperatures and the limited temperature control authority of passive cooling. Because water molecules have adsorption bands within the wavelengths of interest for SPHEREx’s survey, it is imperative that water contamination be controlled and minimized. In this work, a model is developed for the SPHEREx mission to predict the transport and accumulation of outgassed water onto sensitive payload components. The model utilizes the time dependent thermal profiles of the individual payload components, initial water content, and spacecraft geometry to calculate the time dependent water diffusion, transport, and adsorption. This model is subsequently used to predict water contamination risks and design decontamination solutions for each risk. Two major water contamination risks were predicted, water accumulation during cooldown and on cryogenic surfaces during the mission. The first risk occurs during the cooldown of the payload to cryogenic temperatures, predicting water accumulation on optical surfaces in excess of the allowable levels. To mitigate this accumulation, the temperature of the optical surfaces is controlled during cooldown through a combination of heaters and spacecraft pointing. The second risk is that over the course of the mission, is unavoidable water accumulation onto the payload thermal system’s cryogenic surfaces, possibly jeopardizing thermal performance and temperature stability, both of which are required for science success. To decontaminate any water that had collected onto cryogenic thermal system surfaces, a decontamination maneuver was designed. In this decontamination maneuver, cryogenic surfaces of the thermal system are warmed to a temperature where water will desorb by spacecraft pointing while still meeting all avoidance constraints, and thereby avoiding undue risk to the observatory hardware. Through application of the developed analytical model and inclusion of the decontamination maneuver in the mission design, SPHEREx can confidently demonstrate that it is able to decontaminate, at the start of and during the mission as needed to meet its end of life science performance requirements.

Soares, Carolos E.↗

Relating Risk and Reliability Predictions to Design and Development Choices

In this context there are many possible assurance activities. Some focus on the prevention of defects - for example, up-front planning, adoption of design standards, configuration management, training, etc. Others focus on the detection of defects - either to detect latent defects in a system (and so be able to correct them before actual deployment of the system), or to increase confidence that such defects are not present. For example, a wide gamut of reviews, design walkthroughs, tests, inspections, analyses, etc. can be applied to systems and their components.

optimization↗

Predictions of Leukemia Risks to Astronauts from Solar Particle Events

Leukemias consisting of acute and chronic myeloid leukemia and acute lymphatic lymphomas represent the earliest cancers that appear after radiation exposure, have a high lethality fraction, and make up a significant fraction of the overall fatal cancer risk from radiation for adults. Several considerations impact the recommendation of a preferred model for the estimation of leukemia risks from solar particle events (SPE's): The BEIR VII report recommends several changes to the method of calculation of leukemia risk compared to the methods recommended by the NCRP Report No. 132 including the preference of a mixture model with additive and multiplicative components in BEIR VII compared to the additive transfer model recommended by NCRP Report No. 132. Proton fluences and doses vary considerably across marrow regions because of the characteristic spectra of primary solar protons making the use of an average dose suspect. Previous estimates of bone marrow doses from SPE's have used an average body-shielding distribution for marrow based on the computerized anatomical man model (CAM). We have developed an 82-point body-shielding distribution that faithfully reproduces the mean and variance of SPE doses in the active marrow regions (head and neck, chest, abdomen, pelvis and thighs) allowing for more accurate estimation of linear- and quadratic-dose components of the marrow response. SPE's have differential dose-rates and a pseudo-quadratic dose response term is possible in the peak-flux period of an event. Also, the mechanistic basis for leukemia risk continues to improve allowing for improved strategies in choosing dose-rate modulation factors and radiation quality descriptors. We make comparisons of the various choices of the components in leukemia risk estimates in formulating our preferred model. A major finding is that leukemia could be the dominant risk to astronauts for a major solar particle event.

Cucinotta, F. A.↗

Cancer Risk Assessment for Space Radiation

Predicting the occurrence of human cancer following exposure to any agent causing genetic damage is a difficult task. This is because the uncertainty of uniform exposure to the damaging agent, and the uncertainty of uniform processing of that damage within a complex set of biological variables, degrade the confidence of predicting the delayed expression of cancer as a relatively rare event within any given clinically normal individual. The radiation health research priorities for enabling long-duration human exploration of space were established in the 1996 NRC Report entitled "Radiation Hazards to Crews of Interplanetary Missions: Biological Issues and Research Strategies". This report emphasized that a 15-fold uncertainty in predicting radiation-induced cancer incidence must be reduced before NASA can commit humans to extended interplanetary missions. That report concluded that the great majority of this uncertainty is biologically based, while a minority is physically based due to uncertainties in radiation dosimetry and radiation transport codes. Since that report, the biologically based uncertainty has remained large, and the relatively small uncertainty associated with radiation dosimetry has increased due to the considerations raised by concepts of microdosimetry. In a practical sense, however, the additional uncertainties introduced by microdosimetry are encouraging since they are in a direction of lowered effective dose absorbed through infrequent interactions of any given cell with the high energy particle component of space radiation. The biological uncertainty in predicting cancer risk for space radiation derives from two primary facts. 1) One animal tumor study has been reported that includes a relevant spectrum of particle radiation energies, and that is the Harderian gland model in mice. Fact #1: Extension of cancer risk from animal models, and especially from a single study in an animal model, to humans is inherently uncertain. 2) One human database is predominantly used for assessing cancer risk caused by space radiation, and that is the Japanese atomic bomb survivors. Fact #2: The atomic-bomb-survivor database, itself a remarkable achievement, contains uncertainties. These include the actual exposure to each individual, the radiation quality of that exposure, and the fact that the exposure was to acute doses of predominantly low-LET radiation, not to chronic exposures of high-LET radiation expected on long-duration interplanetary manned missions.

Richmond, Robert C.↗

Supply and Resource Management to Progressively Enable EIMO

BACKGROUND: Current medical operations in Low Earth Orbit (LEO) allow for real-time audio-video communication with a flight surgeon at mission control, resupply, and medical evacuation to earth on the order of hours. As mission profiles change from LEO to the Moon, Mars, and beyond, medical risk as a contribution to overall mission risk is anticipated to rise substantially. Concurrently, due to the distance, the medical systems on board vehicles proposed for these mission types are expected to have reduced mass and volume allocation. Together, astronaut crews will be at a higher risk of major medical events, be required to perform a broader set of tasks, and have substantially reduced resources and support to do so. Earth Independent Medical Operations (EIMO) aims to identify and fill the gaps present in this progressively changing paradigm. OVERVIEW: Medical supplies, resources, and skills are central to spaceflight medical systems. Vehicles used for non-LEO missions are anticipated to be smaller and thus the medical system will also need to have reduced mass, volume, and power. Medical resources are another form of consumable and may need resupply or pre-deployment to meet crew needs. One particular concern is the degradation of medications which become less efficacious and potentially toxic with time, particularly given environmental conditions such as temperature, humidity, oxygen, and radiation which have not yet been fully studied. Supply and resource management in LEO is dependent on resupply, however the supply chain of transporting equipment does not yet have a clear infrastructure for missions beyond LEO. DISCUSSION: EIMO is intended to systemically identify and fill these gaps with forward-looking solutions. In mission monitoring of resources with technology like RFID, improving medical resource longevity, targeted resupply and careful pre-mission planning will be central to facilitate crew health and performance. One approach to optimizing resources is the Informing Mission Planning via Analysis of Complex Tradespaces (IMPACT) tool, which uses probabilistic risk assessment (PRA) to quantitatively predict medical risk and identify resources and skills that mitigate this risk. This evidence based, quantitative analysis prediction tool and several other approaches to meeting the challenge of supply and resource management are discussed.

Arian Anderson↗

On the estimation of risk associated with an attenuation prediction

Viewgraphs from a presentation on the estimation of risk associated with an attenuation prediction is presented. Topics covered include: link failure - attenuation exceeding a specified threshold for a specified time interval or intervals; risk - the probability of one or more failures during the lifetime of the link or during a specified accounting interval; the problem - modeling the probability of attenuation by rainfall to provide a prediction of the attenuation threshold for a specified risk; and an accounting for the inadequacy of a model or models.

Crane, R. K.↗

A Dynamic Model for the Evaluation of Aircraft Engine Icing Detection and Control-Based Mitigation Strategies

Aircraft flying in regions of high ice crystal concentrations are susceptible to the buildup of ice within the compression system of their gas turbine engines. This ice buildup can restrict engine airflow and cause an uncommanded loss of thrust, also known as engine rollback, which poses a potential safety hazard. The aviation community is conducting research to understand this phenomena, and to identify avoidance and mitigation strategies to address the concern. To support this research, a dynamic turbofan engine model has been created to enable the development and evaluation of engine icing detection and control-based mitigation strategies. This model captures the dynamic engine response due to high ice water ingestion and the buildup of ice blockage in the engines low pressure compressor. It includes a fuel control system allowing engine closed-loop control effects during engine icing events to be emulated. The model also includes bleed air valve and horsepower extraction actuators that, when modulated, change overall engine operating performance. This system-level model has been developed and compared against test data acquired from an aircraft turbofan engine undergoing engine icing studies in an altitude test facility and also against outputs from the manufacturers customer deck. This paper will describe the model and show results of its dynamic response under open-loop and closed-loop control operating scenarios in the presence of ice blockage buildup compared against engine test cell data. Planned follow-on use of the model for the development and evaluation of icing detection and control-based mitigation strategies will also be discussed. The intent is to combine the model and control mitigation logic with an engine icing risk calculation tool capable of predicting the risk of engine icing based on current operating conditions. Upon detection of an operating region of risk for engine icing events, the control mitigation logic will seek to change the engines operating point to a region of lower risk through the modulation of available control actuators while maintaining the desired engine thrust output. Follow-on work will assess the feasibility and effectiveness of such control-based mitigation strategies.

engine control↗

A Dynamic Model for the Evaluation of Aircraft Engine Icing Detection and Control-Based Mitigation Strategies

Aircraft flying in regions of high ice crystal concentrations are susceptible to the buildup of ice within the compression system of their gas turbine engines. This ice buildup can restrict engine airflow and cause an uncommanded loss of thrust, also known as engine rollback, which poses a potential safety hazard. The aviation community is conducting research to understand this phenomena, and to identify avoidance and mitigation strategies to address the concern. To support this research, a dynamic turbofan engine model has been created to enable the development and evaluation of engine icing detection and control-based mitigation strategies. This model captures the dynamic engine response due to high ice water ingestion and the buildup of ice blockage in the engines low pressure compressor. It includes a fuel control system allowing engine closed-loop control effects during engine icing events to be emulated. The model also includes bleed air valve and horsepower extraction actuators that, when modulated, change overall engine operating performance. This system-level model has been developed and compared against test data acquired from an aircraft turbofan engine undergoing engine icing studies in an altitude test facility and also against outputs from the manufacturers customer deck. This paper will describe the model and show results of its dynamic response under open-loop and closed-loop control operating scenarios in the presence of ice blockage buildup compared against engine test cell data. Planned follow-on use of the model for the development and evaluation of icing detection and control-based mitigation strategies will also be discussed. The intent is to combine the model and control mitigation logic with an engine icing risk calculation tool capable of predicting the risk of engine icing based on current operating conditions. Upon detection of an operating region of risk for engine icing events, the control mitigation logic will seek to change the engines operating point to a region of lower risk through the modulation of available control actuators while maintaining the desired engine thrust output. Follow-on work will assess the feasibility and effectiveness of such control-based mitigation strategies.

engine control↗

Radiation Risk Assessment of the Individual Astronaut: A Complement to Radiation Interests at the NIH

Predicting human risks following exposure to space radiation is uncertain in part because of unpredictable distribution of high-LET and low-dose-derived damage amongst cells in tissues, unknown synergistic effects of microgravity upon gene- and protein-expression, and inadequately modeled processing of radiation-induced damage within cells to produce rare and late-appearing malignant cancers. Furthermore, estimation of risks of radiogenic outcome within small numbers of astronauts is not possible using classic epidemiologic study. It therefore seems useful to develop strategies of risk-assessment based upon large datasets acquired from correlated biological models useful for resolving radiogenic risk-assessment for irradiated individuals. In this regard, it is suggested that sensitive cellular biodosimeters that simultaneously report 1) the quantity of absorbed dose after exposure to ionizing radiation, 2) the quality of radiation delivering that dose, and 3) the biomolecular risk of malignant transformation be developed in order to resolve these NASA-specific challenges. Multiparametric cellular biodosimeters could be developed using analyses of gene-expression and protein-expression whereby large datasets of cellular response to radiation-induced damage are analyzed for markers predictive for acute response as well as cancer-risk. A new paradigm is accordingly addressed wherein genomic and proteomic datasets are registered and interrogated in order to provide statistically significant dose-dependent risk estimation in individual astronauts. This evaluation of the individual for assessment of radiogenic outcomes connects to NIH program in that such a paradigm also supports assignment of a given patient to a specific therapy, the diagnosis of response of that patient to therapy, and the prediction of risks accumulated by that patient during therapy - such as risks incurred by scatter and neutrons produced during high-energy Intensity-Modulated Radiation Therapy. Value of assessment of radiogenic outcome for individuals exposed to radiation is suggested to be common to both NASA and NIH.

Richmond, Robert C.↗

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↗

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↗

The Integrated Medical Model: Statistical Forecasting of Risks to Crew Health and Mission Success

The Integrated Medical Model (IMM) helps capture and use organizational knowledge across the space medicine, training, operations, engineering, and research domains. The IMM uses this domain knowledge in the context of a mission and crew profile to forecast crew health and mission success risks. The IMM is most helpful in comparing the risk of two or more mission profiles, not as a tool for predicting absolute risk. The process of building the IMM adheres to Probability Risk Assessment (PRA) techniques described in NASA Procedural Requirement (NPR) 8705.5, and uses current evidence-based information to establish a defensible position for making decisions that help ensure crew health and mission success. The IMM quantitatively describes the following input parameters: 1) medical conditions and likelihood, 2) mission duration, 3) vehicle environment, 4) crew attributes (e.g. age, sex), 5) crew activities (e.g. EVA's, Lunar excursions), 6) diagnosis and treatment protocols (e.g. medical equipment, consumables pharmaceuticals), and 7) Crew Medical Officer (CMO) training effectiveness. It is worth reiterating that the IMM uses the data sets above as inputs. Many other risk management efforts stop at determining only likelihood. The IMM is unique in that it models not only likelihood, but risk mitigations, as well as subsequent clinical outcomes based on those mitigations. Once the mathematical relationships among the above parameters are established, the IMM uses a Monte Carlo simulation technique (a random sampling of the inputs as described by their statistical distribution) to determine the probable outcomes. Because the IMM is a stochastic model (i.e. the input parameters are represented by various statistical distributions depending on the data type), when the mission is simulated 10-50,000 times with a given set of medical capabilities (risk mitigations), a prediction of the most probable outcomes can be generated. For each mission, the IMM tracks which conditions occurred and decrements the pharmaceuticals and supplies required to diagnose and treat these medical conditions. If supplies are depleted, then the medical condition goes untreated, and crew and mission risk increase. The IMM currently models approximately 30 medical conditions. By the end of FY2008, the IMM will be modeling over 100 medical conditions, approximately 60 of which have been recorded to have occurred during short and long space missions.

Fitts, M. A.↗

Uncertainty Considerations for Ballistic Limit Equations

The overall risk for any spacecraft system is typically determined using a Probabilistic Risk Assessment (PRA). A PRA attempts to determine the overall risk associated with a particular mission by factoring in all known risks (and their corresponding uncertainties, if known) to the spacecraft during its mission. The threat to mission and human life posed by the mircro-meteoroid & orbital debris (MMOD) environment is one of the risks. NASA uses the BUMPER II program to provide point estimate predictions of MMOD risk for the Space Shuttle and the International Space Station. However, BUMPER II does not provide uncertainty bounds or confidence intervals for its predictions. With so many uncertainties believed to be present in the models used within BUMPER II, providing uncertainty bounds with BUMPER II results would appear to be essential to properly evaluating its predictions of MMOD risk. The uncertainties in BUMPER II come primarily from three areas: damage prediction/ballistic limit equations, environment models, and failure criteria definitions. In order to quantify the overall uncertainty bounds on MMOD risk predictions, the uncertainties in these three areas must be identified. In this paper, possible approaches through which uncertainty bounds can be developed for the various damage prediction and ballistic limit equations encoded within the shuttle and station versions of BUMPER II are presented and discussed. We begin the paper with a review of the current approaches used by NASA to perform a PRA for the Space Shuttle and the International Space Station, followed by a review of the results of a recent sensitivity analysis performed by NASA using the shuttle version of the BUMPER II code. Following a discussion of the various equations that are encoded in BUMPER II, we propose several possible approaches for establishing uncertainty bounds for the equations within BUMPER II. We conclude with an evaluation of these approaches and present a recommendation regarding which of them would be the most appropriate to follow.

Schonberg, W. P.↗

Radiation-Induced Leukemia at Doses Relevant to Radiation Therapy: Modeling Mechanisms and Estimating Risks

Because many cancer patients are diagnosed earlier and live longer than in the past, second cancers induced by radiation therapy have become a clinically significant issue. An earlier biologically based model that was designed to estimate risks of high-dose radiation induced solid cancers included initiation of stem cells to a premalignant state, inactivation of stem cells at high radiation doses, and proliferation of stem cells during cellular repopulation after inactivation. This earlier model predicted the risks of solid tumors induced by radiation therapy but overestimated the corresponding leukemia risks. Methods: To extend the model to radiation-induced leukemias, we analyzed in addition to cellular initiation, inactivation, and proliferation a repopulation mechanism specific to the hematopoietic system: long-range migration through the blood stream of hematopoietic stem cells (HSCs) from distant locations. Parameters for the model were derived from HSC biologic data in the literature and from leukemia risks among atomic bomb survivors v^ ho were subjected to much lower radiation doses. Results: Proliferating HSCs that migrate from sites distant from the high-dose region include few preleukemic HSCs, thus decreasing the high-dose leukemia risk. The extended model for leukemia provides risk estimates that are consistent with epidemiologic data for leukemia risk associated with radiation therapy over a wide dose range. For example, when applied to an earlier case-control study of 110000 women undergoing radiotherapy for uterine cancer, the model predicted an excess relative risk (ERR) of 1.9 for leukemia among women who received a large inhomogeneous fractionated external beam dose to the bone marrow (mean = 14.9 Gy), consistent with the measured ERR (2.0, 95% confidence interval [CI] = 0.2 to 6.4; from 3.6 cases expected and 11 cases observed). As a corresponding example for brachytherapy, the predicted ERR of 0.80 among women who received an inhomogeneous low-dose-rate dose to the bone marrow (mean = 2.5 Gy) was consistent with the measured ERR (0.62, 95% Cl =-0.2 to 1.9). Conclusions: An extended, biologically based model for leukemia that includes HSC initiation, inactivation, proliferation, and, uniquely for leukemia, long-range HSC migration predicts, %Kith reasonable accuracy, risks for radiationinduced leukemia associated with exposure to therapeutic doses of radiation.

Shuryak, Igor↗

Method for improved prediction of bone fracture risk using bone mineral density in structural analysis

A non-invasive in-vivo method of analyzing a bone for fracture risk includes obtaining data from the bone such as by computed tomography or projection imaging which data represents a measure of bone material characteristics such as bone mineral density. The distribution of the bone material characteristics is used to generate a finite element method (FEM) mesh from which load capability of the bone can be determined. In determining load capability, the bone is mathematically compressed, and stress, strain force, force/area versus bone material characteristics are determined.

Cann, Christopher E.↗