Risk-adjusted mission value
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As an intern this summer in the GRC Risk Management Office, I have become familiar with the NASA Continuous Risk Management Process. In this process, risk is considered in terms of the probability that an undesired event will occur and the impact of the event, should it occur (ref., NASA-NPG: 7120.5). Risk management belongs in every part of every project and should be ongoing from start to finish. Another key point is that a risk is not a problem until it has happened. With that in mind, there is a six step cycle for continuous risk management that prevents risks from becoming problems. The steps are: identify, analyze, plan, track, control, and communicate & document. Incorporated in the first step are several methods to identify risks such as brainstorming and using lessons learned. Once a risk is identified, a risk statement is made on a risk information sheet consisting of a single condition and one or more consequences. There can also be a context section where the risk is explained in more detail. Additionally there are three main goals of analyzing a risk, which are evaluate, classify, and prioritize. Here is where a value is given to the attributes of a risk &e., probability, impact, and timeframe) based on a multi-level classification system (e.g., low, medium, high). It is important to keep in mind that the definitions of these levels are probably different for each project. Furthermore the risks can be combined into groups. Then, the risks are prioritized to see what risk is necessary to mitigate first. After the risks are analyzed, a plan is made to mitigate as many risks as feasible. Each risk should be assigned to someone in the project with knowledge in the area of the risk. Then the possible approaches to choose from are: research, accept, watch, or mitigate. Next, all risks, mitigated or not, are tracked either individually or in groups. As the plan is executed, risks are re-evaluated, and the attribute values are adjusted as necessary. Metrics are established and monitored as tools for risk tracking. Also a trigger or threshold should be set on the metric data that indicates when an action is needed. Results of this tracking are usually evaluated and reported in a relevant format at weekly or monthly meetings. Choosing controls is the subsequent step, which involves the effects of the tracking. The three basic controls are: close, continue tracking, and re- plan. Finally communicate & document is the last step, but occurs throughout the process. It is vital that main risks, plans, changes, and progress are known by everyone in the project. A good way to keep everyone updated and inform other projects of common issues is by thoroughly documenting project risks. NASA sees value in risk management and believes that projects have greater probability or success by using the NASA Continuous Risk Management Process.
Air pollution poses a serious threat to children’s respiratory health around the world. Satellite remote-sensing technology and air quality models can provide pollution data on a global scale, necessary for riskcommunication efforts in regions without ground-based monitoring networks. Several large centers, including NASA, produce global pollution forecasts that may be used alongside air quality indices to communicate local, daily risk information to the public. Here we present a health-based, globally applicable air quality index developed specifically to reflect the respiratory health risks among children exposed to elevated outdoor air pollution. Additive, excess-risk air quality indices were developed using 51 different coefficients derived from time-series health studies evaluating the impacts of ambient fine particulate matter, nitrogen dioxide, and ozone on children's respiratory morbidity outcomes. A total of four indices were created which varied based on whether or not the underlying studies controlled for co-pollutants and in the adjustment of excess risks of individual pollutants. Combined with historical estimates of air pollution provided globally at a 25x25 km2 spatial resolution from the NASA's Goddard Earth Observing System composition forecast (GEOS-CF) model, each of these indices were examined in a global sample of 664 small and 140 large cities for study year 2017. Adjusted indices presented the most normal distributions of locally-scaled index values, which has been shown to improve associations with health risks, while indices based on coefficients controlling for co-pollutants had little effect on index performance. We provide the steps and resources need to apply our final adjusted index at the local level using freely-available forecasting data from the GEOS-CF model, which can provide risk communication information for cities around the world to better inform individual behavior modification to best protect children's respiratory health.
To date, cytogenetic damage has been assessed in blood lymphocytes from more than 30 astronauts before and after they participated in long-duration space missions of three months or more on board the International Space Station. Chromosome damage was assessed using fluorescence in situ hybridization whole chromosome analysis techniques. For all individuals, the frequency of chromosome damage measured within a month of return from space was higher than their preflight yield, and biodosimetry estimates were within the range expected from physical dosimetry. Follow up analyses have been performed on most of the astronauts at intervals ranging from around 6 months to many years after flight, and the cytogenetic effects of repeat long-duration missions have so far been assessed in four individuals. Chromosomal aberrations in peripheral blood lymphocytes have been validated as biomarkers of cancer risk and cytogenetic damage can therefore be used to characterize excess health risk incurred by individual crewmembers after their respective missions. Traditional risk assessment models are based on epidemiological data obtained on Earth in cohorts exposed predominantly to acute doses of gamma-rays, and the extrapolation to the space environment is highly problematic, involving very large uncertainties. Cytogenetic damage could play a key role in reducing uncertainty in risk estimation because it is incurred directly in the space environment, using specimens from the astronauts themselves. Relative cancer risks were estimated from the biodosimetry data using the quantitative approach derived from the European Study Group on Cytogenetic Biomarkers and Health database. Astronauts were categorized into low, medium, or high tertiles according to their yield of chromosome damage. Age adjusted tertile rankings were used to estimate cancer risk and results were compared with values obtained using traditional modeling approaches. Individual tertile rankings increased after space flight and analysis of follow up samples indicated that the tertile rankings remained in the high category for more than 50% of the individuals assessed so far. Crewmembers that shift and remain in the high category are projected to have increased life-time cancer risk.
With radon and its daughter products estimated as the second leading cause of lung cancer in the United States, it is imperative to understand their relative equilibrium inside commercial, community, and residential dwellings. The radon indoor inhalation fractional equilibrium factor (F eq ) quantifies the disequilibrium between radon and its progeny in indoor air, and recent advances have shown how air exchange rates (ACH) influence F eq . These numerically derived ACH-dependent F eq values are incorporated into the U.S. EPA's Radon Vapor Intrusion Screening Level (RVISL) calculator, which assists risk assessors in evaluating radon exposure. To advance the risk assessment science of actinon (Rn-219), thoron (Rn-220), and radon (Rn-222), the impact of variables such as indoor aerosol concentration and composition, outdoor air quality, household-specific characteristics, and environmental/meteorological conditions on the F eq must be examined. The primary objective of this research is to analyze these additional variables to determine the usefulness of incorporating such adjustment factors into the RVISL calculator and to identify areas of future research. Studies regarding the influence of these parameters are presented along with recommendations regarding the adjustment of the numerically derived F eq value. For example, elevated indoor aerosol concentrations, such as those originating from outdoor PM 2.5 or cigarette smoke, increase the abundance of accumulation- mode particles indoors, which in turn raises F eq values by facilitating the attachment of radon progeny to these aerosols. Smoking increases both the bronchial dose and F eq , while regions with high smog levels demonstrate the impact of regional air quality on F eq . In contrast, air cleaning systems and purifiers have been shown to reduce the F eq , suggesting that these systems could help mitigate radon exposure. Additionally, higher F eq values are typically observed during winter when ventilation rates are lower. This paper presents adjustment factors that may be applied to the RVISL F eq , emphasizing the need for further research to refine these variables and ensure accurate risk assessments in diverse environments. Applying these adjustment factors will minimize calculator over- and underestimations, providing a more accurate representation of the real-world risk associated with radon.
As part of the Constellation (Cx) Program development effort, several test flights were planned to prove concepts and operational capabilities of the new vehicles being developed. The first test, involving the Eastern Test Range, is the Ares I-X launched in 2009. As part of this test, the risk to the general public was addressed to ensure it is within Air Force requirements. This paper describes the methodology used to develop first flight estimates of overall loss of vehicle (LOV) failure probability, specifically for the Ares I-X. The method described in this report starts with the Air Force s generic failure probability estimate for first flight and adjusts the value based on the complexity of the vehicle as compared to the complexity of a generic vehicle. The results estimate a 1 in 9 probability of failure. The paper also describes traditional PRA methods used in this assessment, which were then combined with the updated first flight risk methodology to generate inputs required by the malfunction turn analysis to support estimate of casualty (Ec) calculations as part of the Final Flight Data Package (FFDP) delivered to the Eastern Range for Final Flight Plan Approval.
Background: Carotid Intima Media Thickness (CIMT) has been demonstrated to be predictive of future cardiovascular events. Within various populations, radiation exposure, stress, and physical confinement have all been linked to an increased CIMT. Recent research discovered CIMT was significantly increased in ten long duration astronauts from pre-flight to four days post flight. The relationship between spaceflight and CIMT is not understood and trends in CIMT within the larger astronaut population are unknown. Methods: In 2010, CIMT was offered as part of the astronaut annual exam at the JSC Flight Medicine Clinic using a standardized CIMT screening protocol and professional sonographers. Between 2010 and 2016, CIMT measurements were collected on 213 NASA astronauts and payload specialists. The values used in this retrospective chart review are the mean of the CIMT from the right and left. Spaceflight exposure was categorized based on the total number of days spent in space at the time of the ground-based ultrasound (0, 1-29, 30-100, 101-200, ≥200). Linear regression with generalized estimating equations were used to estimate the association between spaceflight exposures and CIMT. Results: 530 studies were completed among 213 astronauts with a mean of 2.5 studies (range 1-6) per astronaut over the six year period. As in other populations, CIMT was significantly associated with age; however, gender was not. While there was no significant direct correlation between total spaceflight exposure and CIMT found, astronauts with 30-100 spaceflight days and astronauts with greater than 100 spaceflight days had significantly increased CIMT over astronauts who had never flown (p=0.002 and p=<0.0001 respectively) after adjustment for age. Conclusion: Further work is needed to fully understand CIMT and its association to spaceflight. Current occupational surveillance activities are under way to study CIMT values in conjunction with other cardiovascular risk factors among astronauts as compared to the general population.
In most cost estimating applications at the NASA Langley Research Center (LaRC), it is desirable to present predicted cost as a range of possible costs rather than a single predicted cost. A cost risk analysis generates a range of cost for a project and assigns a probability level to each cost value in the range. Constructing a cost risk curve requires a good estimate of the expected cost of a project. It must also include a good estimate of expected variance of the cost. Many cost risk analyses are based upon an expert's knowledge of the cost of similar projects in the past. In a common scenario, a manager or engineer, asked to estimate the cost of a project in his area of expertise, will gather historical cost data from a similar completed project. The cost of the completed project is adjusted using the perceived technical and economic differences between the two projects. This allows errors from at least three sources. The historical cost data may be in error by some unknown amount. The managers' evaluation of the new project and its similarity to the old project may be in error. The factors used to adjust the cost of the old project may not correctly reflect the differences. Some risk analyses are based on untested hypotheses about the form of the statistical distribution that underlies the distribution of possible cost. The usual problem is not just to come up with an estimate of the cost of a project, but to predict the range of values into which the cost may fall and with what level of confidence the prediction is made. Risk analysis techniques that assume the shape of the underlying cost distribution and derive the risk curve from a single estimate plus and minus some amount usually fail to take into account the actual magnitude of the uncertainty in cost due to technical factors in the project itself. This paper addresses a cost risk method that is based on parametric estimates of the technical factors involved in the project being costed. The engineering process parameters are elicited from the engineer/expert on the project and are based on that expert's technical knowledge. These are converted by a parametric cost model into a cost estimate. The method discussed makes no assumptions about the distribution underlying the distribution of possible costs, and is not tied to the analysis of previous projects, except through the expert calibrations performed by the parametric cost analyst.
The protocol for charging a lithium-ion battery would be modified, according to a proposal, to compensate for the internal voltage drop (charging current internal resistance of the battery). The essence of the modification is to provide for measurement of the internal voltage drop and to increase the terminal-voltage setting by the amount of the internal voltage drop. Ordinarily, a lithium-ion battery is charged at constant current until its terminal voltage attains a set value equal to the nominal full-charge potential. The set value is chosen carefully so as not to exceed the lithium-plating potential, because plated lithium in metallic form constitutes a hazard. When the battery is charged at low temperature, the internal voltage drop is considerable because the electrical conductivity of the battery electrolyte is low at low temperature. Charging the battery at high current at any temperature also gives rise to a high internal voltage drop. In some cases, the internal voltage drop can be as high as 1 volt per cell. Because the voltage available for charging is less than the terminal voltage by the amount of the internal voltage drop, the battery is not fully charged (see figure), even when the terminal voltage reaches the set value. In the modified protocol, the charging current would be periodically interrupted so that the zero-current battery-terminal voltage indicative of the state of charge could be measured. The terminal voltage would also be measured at full charging current. The difference between the full-current and zero-current voltages would equal the internal voltage drop. The set value of terminal voltage would then be increased beyond the nominal full-charge potential by the amount of the internal voltage drop. This adjustment would be performed repeatedly, in real time, so that the voltage setting would track variations in the internal voltage drop to afford full charge without risk of lithium plating. If the charging current and voltage settings were controlled by a computer, then this method of charge control could readily be implemented in software.
Satellite conjunction assessment risk analysis is a subjective enterprise that can benefit from quantitative aids and, to this end, NASA/GSFC has developed a fuzzy logic construct - called the F-value - to attempt to provide a statement of conjunction risk that amalgamates multiple indices and yields a more stable intra-event assessment. This construct has now sustained an extended tuning procedure against heuristic analyst assessment of event risk. The tuning effort has resulted in modifications to the calculation procedure and the adjustment of tuning coefficients, producing a construct with both more predictive force and a better statement of its error.
To determine whether measurement of hip and spine bone mass by dual-energy x-ray absorptiometry (DEXA) predicts fractures in women and to compare the predictive value of DEXA with that of single-photon absorptiometry (SPA) of appendicular sites, we prospectively studied 8134 nonblack women age 65 years and older who had both DEXA and SPA measurements of bone mass. A total of 208 nonspine fractures, including 37 wrist fractures, occurred during the follow-up period, which averaged 0.7 years. The risk of fracture was inversely related to bone density at all measurement sites. After adjusting for age, the relative risks per decrease of 1 standard deviation in bone density for the occurrence of any fracture was 1.40 for measurement at the proximal femur (95% confidence interval 1.20-1.63) and 1.35 (1.15-1.58) for measurement at the spine. Results were similar for all regions of the proximal femur as well as SPA measurements at the calcaneus, distal radius, and proximal radius. None of these measurements was a significantly better predictor of fractures than the others. Furthermore, measurement of the distal radius was not a better predictor of wrist fracture (relative risk 1.64: 95% CI 1.13-2.37) than other sites, such as the lumbar spine (RR 1.56; CI 1.07-2.26), the femoral neck (RR 1.65; CI 1.12-2.41), or the calcaneus (RR 1.83; CI 1.26-2.64). We conclude that the inverse relationship between bone mass and risk of fracture in older women is similar for absorptiometric measurements made at the hip, spine, and appendicular sites.
One of the most significant occupational hazards to an astronaut is the frequent exposure to radiation. Commonly associated with increased risk for cancer related morbidity and mortality, radiation is also known to increase the risk for cardiovascular related disorders including: pericarditis, hypertension, and heart failure. It is believed that these radiation-induced disorders are a result of abnormal tissue remodeling. It is unknown whether radiation exposure promotes remodeling through fibrotic changes alone or in combination with programmed cell death. Furthermore, it is not known whether it is possible to mitigate the hazardous effects of radiation exposure. As such, we assessed the expression and mechanisms of radiation-induced tissue remodeling and potential radio-adaptive responses of p53-mediated apoptosis and fibrosis pathways along with markers for oxidative stress and inflammation in mice myocardium. 7 week old, male, C57Bl/6 mice were exposed to 6Gy (H) or 5cGy followed 24hr later with 6Gy (LH) 137Cs gamma radiation. Mice were sacrificed and their hearts extirpated 4, 24, or 72hr after final irradiation. Real Time - Polymerase Chain Reaction was used to evaluate target genes. Apoptotic genes Bad and Bax, pro-cell survival genes Bcl2 and Bcl2l2, fibrosis gene Vegfa, and oxidative stress genes Sod2 and GPx4 showed a reduced fold regulation change (Bad,-6.18; Bax,-6.94; Bcl2,-5.09; Bcl2l2,-4.03; Vegfa, -11.84; Sod2,-5.97; GPx4*,-28.72; * = Bonferroni adjusted p-value < or = 0.003) 4hr after H, but not after 4hr LH compared to control. Other p53-mediated apoptosis genes Casp3, Casp9, Trp53, and Myc exhibited down-regulation but did not achieve a notable level of significance 4hr after H. 24hr after H, genetic down-regulation was no longer present compared to 24hr control. These data suggest a general reduction in genetic expression 4hrs after a high dose of gamma radiation. However, pre-exposure to 5cGy gamma radiation appears to facilitate a radio-adaptive response that mitigates the reduction in genetic expression associated with single high-dose gamma radiation exposure. This radio-adaptive response may serve as a potential countermeasure to radiation-induced myocardial remodeling and preserve the cardiovascular health of astronauts; thus, reducing the risks of human space exploration.
One of the most significant occupational hazards to an astronaut is the frequent exposure to radiation. Commonly associated with increased risk for cancer related morbidity and mortality, radiation is also known to increase the risk for cardiovascular related disorders including: pericarditis, hypertension, and heart failure. It is believed that these radiation-induced disorders are a result of abnormal tissue remodeling. It is unknown whether radiation exposure promotes remodeling through fibrotic changes alone or in combination with programmed cell death. Furthermore, it is not known whether it is possible to mitigate the hazardous effects of radiation exposure. As such, we assessed the expression and mechanisms of radiation-induced tissue remodeling and potential radio-adaptive responses of p53-mediated apoptosis and fibrosis pathways along with markers for oxidative stress and inflammation in mice myocardium. 7 week old, male, C57Bl/6 mice were exposed to 6Gy (H) or 5cGy followed 24hr later with 6Gy (LH) Cs-137 gamma radiation. Mice were sacrificed and their hearts extirpated 4, 24, or 72hr after final irradiation. Real Time - Polymerase Chain Reaction was used to evaluate target genes. Pro-apoptotic genes Bad and Bax, pro-cell survival genes Bcl2 and Bcl2l2, fibrosis gene Vegfa, and oxidative stress genes Sod2 and GPx4 showed a reduced fold regulation change (Bad,-6.18; Bax,-6.94; Bcl2,-5.09; Bcl2l2,-4.03; Vegfa, -11.84; Sod2,-5.97; GPx4*,-28.72; * = Bonferroni adjusted p-value . 0.003) 4hr after H, but not after 4hr LH when compared to control. Other p53-mediated apoptosis genes Casp3, Casp9, Trp53, and Myc exhibited down-regulation but did not achieve a notable level of significance 4hr after H. 24hr after H, genetic down-regulation was no longer present compared to 24hr control. These data suggest a general reduction in genetic expression 4hrs after a high dose of gamma radiation. However, pre-exposure to 5cGy gamma radiation appears to facilitate a radio-adaptive response that mitigates the reduction in genetic expression associated with single high-dose gamma radiation exposure. This radio-adaptive response may serve as a potential countermeasure to radiation-induced myocardial remodeling and preserve the cardiovascular health of astronauts; thus, reducing the risks of human space exploration.
A number of new methods have been recently developed to quantify complex heart rate (HR) dynamics based on nonlinear and fractal analysis, but their value in risk stratification has not been evaluated. This study was designed to determine whether selected new dynamic analysis methods of HR variability predict mortality in patients with depressed left ventricular (LV) function after acute myocardial infarction (AMI). Traditional time- and frequency-domain HR variability indexes along with short-term fractal-like correlation properties of RR intervals (exponent alpha) and power-law scaling (exponent beta) were studied in 159 patients with depressed LV function (ejection fraction <35%) after an AMI. By the end of 4-year follow-up, 72 patients (45%) had died and 87 (55%) were still alive. Short-term scaling exponent alpha (1.07 +/- 0.26 vs 0.90 +/- 0.26, p <0.001) and power-law slope beta (-1.35 +/- 0.23 vs -1.44 +/- 0.25, p <0.05) differed between survivors and those who died, but none of the traditional HR variability measures differed between these groups. Among all analyzed variables, reduced scaling exponent alpha (<0.85) was the best univariable predictor of mortality (relative risk 3.17, 95% confidence interval 1.96 to 5.15, p <0.0001), with positive and negative predictive accuracies of 65% and 86%, respectively. In the multivariable Cox proportional hazards analysis, mortality was independently predicted by the reduced exponent alpha (p <0.001) after adjustment for several clinical variables and LV function. A short-term fractal-like scaling exponent was the most powerful HR variability index in predicting mortality in patients with depressed LV function. Reduction in fractal correlation properties implies more random short-term HR dynamics in patients with increased risk of death after AMI.
The last decade has seen a large number of severe heatwaves that were unprecedented in the observational record, highlighting challenges associated with observationally-based statistical quantification of the likelihood and magnitude of future extreme temperatures. An alternative to such probabilistic assessments is identification of upper bounds that quantify the hottest surface air temperatures that can possibly be achieved by the end of the 21st century. Theory, simulations, and observational analyses support the existence of a finite upper bound for surface air temperature; however, estimates for future upper-bound values that are realistic and usable for planning remain unavailable. Here, we combine atmospheric theory with large ensembles of dynamically downscaled projections to estimate historical and end-of-century upper bounds for surface air temperatures. A number of physical mechanisms can influence upper bounds, and at the end of the 21st century, estimates based on mechanisms that yield more moderate upper-bounds produce values around 60∘C for much of the Western United States and in excess of 80∘C for the hottest parts of the domain. Even cooler high-altitude locations have end-of-century upper bounds over 50∘C. Although these upper-bound estimates might seem implausibly large, increases in the upper bounds over the 21st century are similar to increases in dynamically downscaled peak surface temperatures after adjusting those downscaled temperatures to eliminate the possibly biased model trends in surface specific humidity. While upper bound estimates are high relative to historical observations, they nonetheless suggest that heatwave intensity risk is bounded, with uncertainty dominated by projections of surface and upper-level humidity.
This invited presentation describes demonstration of semiconductor integrated circuits (ICs) and ceramic packaging that are arguably the most environmentally durable transistor electronics ever demonstrated. SiC junction field effect transistor-resistor (JFET-R) ICs with two-level interconnect have successfully operated for over 1 year in 500 °C air-ambient [1], 60 days in 460 °C and 9.3 MPa pressure caustic Venus surface environment test chamber [2], and radiation exposure through 7 Mrad(Si) total ionizing dose (TID) and 86 MeV-cm2/mg heavy ion strikes [3]. Furthermore, these ICs have also demonstrated operation from -190 °C to +812 °C (over 1000 °C T-span) without significant change in signal (input /output) or power supply voltages [4]. With modest adjustments, the SiC JFET-R fabrication process is compatible with semiconductor mass-production tools and materials. As an initial step towards this end, the processing that forms the SiC JFETs and resistors (without interconnect) for the NASA Glenn “Generation 12” design prototype JFET-R ICs was conducted at GE Research. Once the COVID-delayed IC interconnect and bond pad fabrication processing on these wafers is completed at NASA Glenn, the resulting chips will be packaged and oven-tested [5]. It is expected that further technology transfer to complete commercial production will lower investment and risk barriers to useful application deployment. For NASA, an initial high-value deployment is opening the Venus surface to extended missions for robotic scientific exploration.
To validate and further improve the Integrated Medical Model (IMM), medical event data were obtained from 32 ISS and 122 STS person-missions. Using the crew characteristics from these observed missions, IMM v4.0 was used to forecast medical events and medical resource utilization. The IMM medical condition incidence values were compared to the actual observed medical event incidence values, and the IMM forecasted medical resource utilization was compared to actual observed medical resource utilization. Qualitative comparisons of these parameters were conducted for both the ISS and STS programs. The results of these analyses will provide validation of IMM v4.0 and reveal areas of the model requiring adjustments to improve the overall accuracy of IMM outputs. This validation effort should result in enhanced credibility of the IMM and improved confidence in the use of IMM as a decision support tool for human space flight.
OBJECTIVE: We sought to assess whether aortic valve replacement (AVR) among patients with severe aortic stenosis (AS), severe left ventricular (LV) dysfunction and a low transvalvular gradient (TVG) is associated with improved survival. BACKGROUND: The optimal management of patients with severe AS with severe LV dysfunction and a low TVG remains controversial. METHODS: Between 1990 and 1998, we evaluated 68 patients who underwent AVR at our institution (AVR group) and 89 patients who did not undergo AVR (control group), with an aortic valve area < or = 0.75 cm(2), LV ejection fraction < or = 35% and mean gradient < or = 30 mm Hg. Using propensity analysis, survival was compared between a cohort of 39 patients in the AVR group and 56 patients in the control group. RESULTS: Despite well-matched baseline characteristics among propensity-matched patients, the one- and four-year survival rates were markedly improved in patients in the AVR group (82% and 78%), as compared with patients in the control group (41% and 15%; p < 0.0001). By multivariable analysis, the main predictor of improved survival was AVR (adjusted risk ratio 0.19, 95% confidence interval 0.09 to 0.39; p < 0.0001). The only other predictors of mortality were age and the serum creatinine level. CONCLUSIONS: Among select patients with severe AS, severe LV dysfunction and a low TVG, AVR was associated with significantly improved survival.