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At least 595 records · Page 33

Wake-Vortex Hazards During Cruise

Even though the hazard posed by lift-generated wakes of subsonic transport aircraft has been studied extensively for approach and departure at airports, only a small amount of effort has gone into the potential hazard at cruise altitude. This paper reports on a studio of the wake-vortex hazard during cruise because encounters may become more prevalent when free-flight becomes available and each aircraft, is free to choose its own route between destinations. In order to address the problem, the various fluid-dynamic stages that vortex wakes usually go through as they age will be described along with estimates of the potential hazard that each stage poses. It appears that a rolling-moment hazard can be just as severe at cruise as for approach at airports, but it only persists for several minutes. However, the hazard posed by the downwash in the wake due to the lift on the generator aircraft persists for tens of minutes in a long narrow region behind the generating aircraft. The hazard consists of severe vertical loads when an encountering aircraft crosses the wake. A technique for avoiding vortex wakes at cruise altitude will be described. To date the hazard posed by lift-generated vortex wakes and their persistence at cruise altitudes has been identified and subdivided into several tasks. Analyses of the loads to be encounter and are underway and should be completed shortly. A review of published literature on the subject has been nearly completed (see text) and photographs of vortex wakes at cruise altitudes have been taken and the various stages of decay have been identified. It remains to study and sort the photographs for those that best illustrate the various stages of decay after they are shed by subsonic transport aircraft at cruise altitudes. The present status of the analysis and the paper are described.

Rossow, Vernon J.↗

Historical Study of Radiation Exposures and the Incidence of Cataracts in Astronauts

For over 35 years, astronauts in low Earth orbit or on missions to the moon have been exposed to space radiation comprised of high-energy protons, heavy ions, and secondary neutrons. We reviewed the radiation exposures received by astronauts in space and on Earth, and presented results from the first epidemiological study of cataract incidence in the astronauts. Our data suggested an increased risk for cataracts from space radiation exposures. Using parametric survival analysis and the maximum likelihood method, we estimated the dose-response and age distribution for cataract incidence in astronauts by space radiation. Considering the high-LET dose contributions on specific space missions as well as data from animal studies with neutrons and heavy ions, suggested a linear response with no dose-threshold for cataracts. However, there are unanswered questions related to the importance and the definition of clinically significant cataracts commonly used in radiation protection, especially in light of epidemiological data suggesting that the probability that sub-clinical cataracts will progress is highly dependent on the age at which cataracts appear. We briefly describe a new study that will address the measurement of cataract progression-rates in astronauts and a ground-based comparison group.

Cucinotta, F. A.↗

Historical Study of Radiation Exposures and the Incidence of Cataracts in Astronauts

For over 35 years, astronauts in low Earth orbit or on missions to the moon have been exposed to space radiation comprised of high-energy protons, heavy ions, and secondary neutrons. We reviewed the radiation exposures received by astronauts in space and on Earth, and presented results from the first epidemiological study of cataract incidence in the astronauts. Our data suggested an increased risk for cataracts from space radiation exposures*. Using parametric survival analysis and the maximum likelihood method, we estimated the dose-response and age distribution for cataract incidence in astronauts by space radiation. Considering the high-LET dose contributions on specific space missions as well as data from animal studies with neutrons and heavy ions, suggested a linear response with no dose-threshold for cataracts. However, there are unanswered questions related to the importance and the definition of "clinically significant" cataracts commonly used in radiation protection, especially in light of epidemiological data suggesting that the probability that "sub-clinical" cataracts will progress is highly dependent on the age at which cataracts appear. We briefly describe a new study that will address the measurement of cataract progression-rates in astronauts and a ground-based comparison group.

Cucinotta, F. A.↗

Volcanism on Mars

Spacecraft exploration has revealed abundant evidence that Mars possesses some of the most dramatic volcanic landforms found anywhere within the solar system. How did a planet half the size of Earth produce volcanoes like Olympus Mons, which is several times the size of the largest volcanoes on Earth? This question is an example of the kinds of issues currently being investigated as part of the space-age scientific endeavor called "comparative planetology." This chapter summarizes the basic information currently known about volcanism on Mars. The volcanoes on Mars appear to be broadly similar in overall morphology (although, often quite different in scale) to volcanic features on Earth, which suggests that Martian eruptive processes are not significantly different from the volcanic styles and processes on Earth. Martian volcanoes are found on terrains of different age, and Martian volcanic rocks are estimated to comprise more than 50% of the Martian surface. This is in contrast to volcanism on smaller bodies such as Earth's Moon, where volcanic activity was mainly confined to the first half of lunar history (see "Volcanism on the Moon"). Comparative planetology supports the concept that volcanism is the primary mechanism for a planetary body to get rid of its internal heat; smaller bodies tend to lose their internal heat more rapidly than larger bodies (although, Jupiter's moon Io appears to contradict this trend; Io's intense volcanic activity is powered by unique gravitational tidal forces within the Jovian system; see "Volcanism on Io"), so that volcanic activity on Mars would be expected to differ considerably from that found on Earth and the Moon.

Mars↗

The Complex Exhumation History of Jezero Crater Floor Unit and Its Implication for Mars Sample Return

During the first year of NASA's Mars 2020 mission, Perseverance rover has investigated the dark crater floor unit of Jezero crater and four samples of this unit have been collected. The focus of this paper is to assess the potential of these samples to calibrate the crater-based Martian chronology. We first review the previous estimation of crater-based model age of this unit. Then, we investigate the impact crater density distribution across the floor unit. It reveals that the crater density is heterogeneous from areas which have been exposed to the bombardment during the last 3 Ga to areas very recently exposed to bombardment. It suggests a complex history of exposure to impact cratering. We also display evidence of several remnants of deposits on the top of the dark floor unit across Jezero below which the dark floor unit may have been buried. We propose the following scenario of burying/exhumation: the dark floor unit would have been initially buried below a unit that was a few tens of meters thick. This unit then gradually eroded away due to Aeolian processes from the northeast to the west, resulting in uneven exposure to impact bombardment over 3 Ga. A cratering model reproducing this scenario confirms the feasibility of this hypothesis. Due to the complexity of its exposure history, the Jezero dark crater floor unit will require additional detailed analysis to understand how the Mars 2020 mission samples of the crater floor can be used to inform the Martian cratering chronology.

Mars 2020↗

Guide to Nondestructive Evaluation Techniques

Nondestructive evaluation (NDE), alternately known as nondestructive examination (NDE), (commonly used within the nuclear industry), nondestructive testing (NDT) (commonly used in the aerospace and petrochemical industry), and nondestructive inspection (NDI) (commonly used within the military), are as the name implies test and assessment technologies designed to detect and characterize components without damaging or compromising the component’s ability to perform its design function. The most common application is detection of flaws caused either by manufacturing anomalies, service or environmental stresses, or natural material aging. More generally, applications may include estimation of mechanical and material properties, stress/strain, and dynamic response behavior. Post-manufacturing inspections frequently enjoy unfettered access to the component or part that may allow more thorough examinations, while in-service examinations after components have been in use may impose severe access limitations for in-situ testing. If flaws are detected, they must then be evaluated relative to their size, location, growth rate, growth mechanism, and likelihood that they are or will become a liability to the component’s function or performance. NDE is comprised of a large family of specific test disciplines including visual inspection, dimensional metrology, ultrasound, radiography, penetrant test, magnetic particle test, leak test, eddy current tests, potential drop tests, flash and vibro thermography, shearography, acoustic emissions, and many other methods. This section provides discussion on general NDE science and considerations for specific technique selection.

nondestructive, examination, inspection, NDE, NDT↗

The evolution of precipitate crystal structures in an Al-Mg-Si(-Cu) alloy studied by a combined HAADF-STEM and SPED approach

Highlights: • Scanning electron diffraction and machine learning complement lattice imaging • Developed approach gives increased objectivity in precipitate phase analysis • Precipitate phase fractions and solute content obtained with superior statistics • 0.01 at.% Cu changes the Al-Mg-Si system precipitation during overageing • Q’-phase eventually dominates precipitate structures and shows varying Cu-occupancy - Abstract: This work presents a detailed investigation into the effect of a low Cu addition (0.01 at.%) on precipitation in an Al-0.80Mg-0.85Si alloy during ageing. The precipitate crystal structures were assessed by scanning transmission electron microscopy combined with a novel scanning precession electron diffraction approach, which includes machine learning. The combination of techniques enabled evaluation of the atomic arrangement within individual precipitates, as well as an improved estimate of precipitate phase fractions at each ageing condition, through analysis of a statistically significant number of precipitates. Based on the obtained results, the total amount of solute atoms locked inside precipitates could be approximated. It was shown that even with a Cu content close to impurity levels, the Al-Mg-Si system precipitation was significantly affected with overageing. The principal change was due to a gradually increasing phase fraction of the Cu-containing Q′-phase, which eventually was seen to dominate the precipitate structures. The structural overtake could be explained based on a continuous formation of the thermally stable Q′-phase, with Cu atomic columns incorporating less Cu than what could potentially be accommodated.

36 MATERIALS SCIENCE↗

C-14 content of ten meteorites measured by tandem accelerator mass spectrometry

Measurements of C-14 in three North American and seven Antarctic meteorites show in most cases that this cosmogenic isotope, which is tightly bound, was separated from absorbed atmospheric radiocarbon by stepwise heating extractions. The present upper limit to age determination by the accelerator method varies from 50,000 to 70,000 years, depending on the mass and carbon content of the sample. The natural limit caused by cosmic ray production of C-14 in silicate rocks at 2000 m elevation is estimated to be 55,000 + or - 5000 years. An estimation is also made of the 'weathering ages' of the Antarctic meteorites from the specific activity of loosely bound CO2 which is thought to be absorbed from the terrestrial atmosphere. Accelerator measurements are found to agree with previous low level counting measurements, but are more sensitive and precise.

Brown, R. M.↗

Apollo 14 regolith breccias - Different glass populations and their potential for charting space time variations

Apollo 14 regolith breccias (14313, 14307, 14301, 14049, 14047) have been found to have different populations of nonagglutinitic, mare-derived glasses. These variations appear to not only reflect different source regoliths but also different closure ages for these breccias. Based upon these different glass populations, 14301 is inferred to have a closure age sometime during the epoch of mare volcanism. All of the other four breccias were formed after the termination of mare volcanism with a possible age sequence from old to young of the following: 14307, 14313, 14049, 14047. Due to the relative simplicity of acquiring high-quality chemical data on large numbers of glasses by electron microprobe, mare glass populations allow: (1) classification of regolith breccias with respect to provenance and (2) estimation of their relative and absolute closure ages. The determination of (Ar-40)-(Ar-39) ages on individual glass spherules within breccias using the laser probe should in the future prove to be a promising extension of the present study.

Delano, John W.↗

Quantile-specific heritability of plasma fibrinogen concentrations

Fibrinogen is a moderately heritable blood protein showing different genetic effects by sex, race, smoking status, pollution exposure, and disease status. These interactions may be explained in part by “quantile-dependent expressivity”, where the effect size of a genetic variant depends upon whether the phenotype (e.g. plasma fibrinogen concentration) is high or low relative to its distribution. Determine whether fibrinogen heritability (h 2 ) is quantile-specific, and whether quantile-specific h 2 could account for fibrinogen gene-environment interactions. Plasma fibrinogen concentrations from 5689 offspring-parent pairs and 1932 sibships from the Framingham Heart Study were analyzed. Quantile-specific heritability from offspring-parent (β OP , h 2 = 2β OP /(1+r spouse )) and full-sib regression slopes (β FS , h 2 = {(1+8r spouse β FS ) 0.05 –1}/(2r spouse )) were robustly estimated by quantile regression with nonparametric significance assigned from 1000 bootstrap samples. Quantile-specific h 2 (±SE) increased with increasing percentiles of the offspring’s age- and sex-adjusted fibrinogen distribution when estimated from β OP (P trend = 5.5x10 -6 ): 0.30±0.05 at the 10 th , 0.37±0.04 at the 25 th , 0.48±0.05 at the 50 th , 0.61±0.06 at the 75 th , and 0.65±0.08 at the 90 th percentile, and when estimated from β FS (P trend = 0.008): 0.28±0.04 at the 10 th , 0.31±0.04 at the 25 th , 0.36±0.03 at the 50 th , 0.41±0.05 at the 75 th , and 0.50±0.06 at the 90 th percentile. The larger genetic effect at higher average fibrinogen concentrations may contribute to fibrinogen’s greater heritability in women than men and in Blacks than Whites, and greater increase from smoking and air pollution for the FGB -455G>A A-allele. It may also explain greater fibrinogen differences between: 1) FGB -455G>A genotypes during acute phase reactions than usual conditions, 2) GTSM1 and IL-6 -572C>G genotypes in smokers than nonsmokers, 3) FGB -148C>T genotypes in untreated than treated diabetics, and LPL PvuII genotypes in macroalbuminuric than normoalbuminuric patients. Fibrinogen heritability is quantile specific, which may explain or contribute to its gene-environment interactions. The analyses do not disprove the traditional gene-environment interpretations of these examples, rather quantile-dependent expressivity provides an alternative explanation that warrants consideration.

59 BASIC BIOLOGICAL SCIENCES↗

Quantile-dependent expressivity of plasma adiponectin concentrations may explain its sex-specific heritability, gene-environment interactions, and genotype-specific response to postprandial lipemia

“Quantile-dependent expressivity” occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g. adiponectin) is high or low relative to its distribution. We have previously shown that the heritability ( h 2 ) of adiposity, lipoproteins, postprandial lipemia, pulmonary function, and coffee and alcohol consumption are quantile-specific. Whether adiponectin heritability is quantile specific remains to be determined. Plasma adiponectin concentrations from 4,182 offspring-parent pairs and 1,662 sibships from the Framingham Heart Study were analyzed. Quantile-specific heritability from offspring-parent (β OP , h 2 = 2 β OP /(1 + r spouse )) and full-sib regression slopes ( β FS , h 2 = {(1 + 8r spouse β FS ) 0.05 -1}/(2r spouse )) were robustly estimated by quantile regression with nonparametric significance assigned from 1,000 bootstrap samples. Quantile-specific h 2 (± SE) increased with increasing percentiles of the offspring’s age- and sex-adjusted adiponectin distribution when estimated from β OP ( P trend = 2.2 × 10 -6 ): 0.30 ± 0.03 at the 10th, 0.33 ± 0.04 at the 25th, 0.43 ± 0.04 at the 50th, 0.55 ± 0.05 at the 75th, and 0.57 ± 0.08 at the 90th percentile, and when estimated from β FS (P trend = 7.6 × 10 -7 ): 0.42 ± 0.03 at the 10th, 0.44 ± 0.04 at the 25th, 0.56 ± 0.05 at the 50th, 0.73 ± 0.08 at the 75th, and 0.79 ± 0.11 at the 90th percentile. Consistent with quantile-dependent expressivity, adiponectin’s: (1) heritability was greater in women in accordance with their higher adiponection concentrations; (2) relationships to ADIPOQ polymorphisms were modified by adiposity in accordance with its adiponectin-lowering effect; (3) response to rosiglitazone was predicted by the 45T> G ADIPOQ polymorphism; (4) difference by ADIPOQ haplotypes increased linearly with increasing postprandial adiponectin concentrations. Adiponectin heritability is quantile dependent, which may explain sex-specific heritability, gene-environment and gene-drug interactions, and postprandial response by haplotypes.

Postprandial↗

Patterns and controls on island‐wide aboveground biomass accumulation in second‐growth forests of Puerto Rico

Abstract Understanding the heterogeneity of biomass accumulation in second‐growth tropical forests following land use abandonment is important for informing ecosystem carbon models and forest restoration efforts. There is an urgent need for a broad sample of second‐growth forests to enhance our knowledge of carbon accumulation in human‐dominated landscapes, especially for older forests. Puerto Rico has predominantly second‐growth forests, ranging in age from approximately 25 to more than 80 years. We used an island‐wide sample of airborne lidar from the NASA Goddard Lidar, Hyperspectral, and Thermal (G‐LiHT) Airborne Imager collected on March 2017, forest inventory data, and data on forest age, precipitation, soils, and land use to estimate aboveground biomass stocks in moist and wet, second‐growth tropical forests. Biomass accumulation rates in Puerto Rico were lower, on average, than in other Neotropical forests. Median biomass across >16,700 ha of older second‐growth forests was 105 Mg ha −1 , and sampled biomass rarely surpassed 250 Mg ha −1 . Differences in biomass by age were large and persistent across different substrates and land uses, with a plateau in the pattern of island‐wide biomass accumulation after about 33 years. A spatial regression model showed that multiple factors were related to biomass accumulation, including time since abandonment, geologic substrate, past land use as coffee or pasture, precipitation, topographic wetness index, and slope. Our findings have important consequences for the total carbon storage and expected climate mitigation benefits of large‐scale reforestation efforts, and highlight the value of airborne lidar for quantifying biomass variability in complex tropical landscapes. Abstract in Spanish is available with online material.

54 ENVIRONMENTAL SCIENCES↗

RAIS Slope Factors for Radionuclides

For a given radionuclide, Slope Factors (SFs) represent the ELCR equivalent per unit intake (i.e., ingestion or inhalation) or external exposure of that radionuclide. These SFs are used to convert a radionuclide concentration in soil, air, water, or foodstuffs to a radiation ELCR. The primary use of SFs, also called risk coefficients, is to compute the ELCR resulting from site-related exposures. This is accomplished by multiplying the route-specific SF by the CDI of each radionuclide of potential concern for each route of exposure. Ingestion and inhalation slope factors are central estimates in a linear model of the age-averaged, lifetime attributable radiation cancer incidence (fatal and nonfatal cancer) risk per unit of activity inhaled or ingested, expressed as risk/picocurie (pCi). External exposure SFs are central estimates of lifetime attributable radiation cancer incidence risk for each year of exposure to external radiation from photon-emitting radionuclides distributed uniformly in a thick layer of soil, expressed as risk/year per pCi/gram soil. External exposure SF units can also be risk/year per pCi/square centimeters (cm2) of soil. When combined with site-specific media concentration data and appropriate exposure assumptions, SFs can be used to estimate lifetime cancer risks to members of the general population due to radionuclide exposures. The SFs presented on are updated values from Federal Guidance Report (FGR) 13 supplement using the International Commission on Radiological Protection (ICRP) 107 decay data. The derivation and values are found in “Calculations of Slope Factors and Dose Coefficients” (ORNL, 2014).

Noto, Katie [Oak Ridge National Laboratory (ORNL),↗

Patterns and Controls on Island-Wide Aboveground Biomass Accumulation in Second-Growth Forests of Puerto Rico

Understanding the heterogeneity of biomass accumulation in second-growth tropical forests following land use abandonment is important for informing ecosystem carbon models and forest restoration efforts. There is an urgent need for a broad sample of second-growth forests to enhance our knowledge of carbon accumulation in human-dominated landscapes, especially for older forests. Puerto Rico has predominantly second-growth forests, ranging in age from approximately 25 to more than 80 years. We used an island-wide sample of airborne lidar from the NASA Goddard Lidar, Hyperspectral, and Thermal (G-LiHT) Airborne Imager collected on March 2017, forest inventory data, and data on forest age, precipitation, soils, and land use to estimate aboveground biomass stocks in moist and wet, second-growth tropical forests. Biomass accumulation rates in Puerto Rico were lower, on average, than in other Neotropical forests. Median biomass across >16,700 ha of older second-growth forests was 105 Mg ha−1, and sampled biomass rarely surpassed 250 Mg ha−1. Differences in biomass by age were large and persistent across different substrates and land uses, with a plateau in the pattern of island-wide biomass accumulation after about 33 years. A spatial regression model showed that multiple factors were related to biomass accumulation, including time since abandonment, geologic substrate, past land use as coffee or pasture, precipitation, topographic wetness index, and slope. Our findings have important consequences for the total carbon storage and expected climate mitigation benefits of large-scale reforestation efforts, and highlight the value of airborne lidar for quantifying biomass variability in complex tropical landscapes.

Sebastián Martinuzzi↗

Generating Older Adult Multimorbidity Trajectories Using Various Comorbidity Indices and Calculation Methods

Older adult multimorbidity trajectories are helpful for understanding the current and future health patterns of aging populations. The construction of multimorbidity trajectories from comorbidity index scores will help inform public health and clinical interventions targeting those individuals that are on unhealthy trajectories. Investigators have used many different techniques when creating multimorbidity trajectories in prior literature, and no standard way has emerged. This study compares and contrasts multimorbidity trajectories constructed from various methods. We describe the difference between aging trajectories constructed with the Charlson Comorbidity Index (CCI) and Elixhauser Comorbidity Index (ECI). We also explore the differences between acute (single year) and chronic (cumulative) derivations of CCI and ECI scores. Social determinants of health can affect disease burden over time; thus, our models include income, race/ethnicity, and sex differences. We use group-based trajectory modeling (GBTM) to estimate multimorbidity trajectories for 86,909 individuals aged 66–75 in 1992 using Medicare claims data collected over the following 21 years. We identify low-chronic disease and high-chronic disease trajectories in all 8 generated trajectory models. Additionally, all 8 models satisfied prior established statistical diagnostic criteria for well-performing GBTM models. Clinicians may use these trajectories to identify patients on an unhealthy path and prompt a possible intervention that may shift the patient to a healthier trajectory.

60 APPLIED LIFE SCIENCES↗

Quantile-dependent expressivity of serum C-reactive protein concentrations in family sets

“Quantile-dependent expressivity” occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g., C-reactive protein, CRP) is high or low relative to its distribution. We have previously shown that the heritabilities ( h 2 ) of coffee and alcohol consumption, postprandial lipemia, lipoproteins, leptin, adiponectin, adiposity, and pulmonary function are quantile-specific. Whether CRP heritability is quantile-specific is currently unknown. Methods Serum CRP concentrations from 2,036 sibships and 6,144 offspring-parent pairs were analyzed from the Framingham Heart Study. Quantile-specific heritability from full-sib (β FS , h 2 ={(1 + 8r spouse β FS ) 0.5 - 1}/(2r spouse )) and offspring-parent regression slopes (β OP , h 2 = 2β OP /(1 + r spouse )) were estimated robustly by quantile regression with nonparametric significance determined from 1,000 bootstrap samples. Results Quantile-specific h 2 (±SE) increased with increasing percentiles of the offspring’s age- and sex-adjusted CRP distribution when estimated from β OP ( P trend = 0.0004): 0.02 ± 0.01 at the 10th, 0.04 ± 0.01 at the 25th, 0.10 ± 0.02 at the 50th, 0.20 ± 0.05 at the 75th, and 0.33 ± 0.10 at the 90th percentile, and when estimated from β FS ( P trend = 0.0008): 0.03±0.01 at the 10th, 0.06 ± 0.02 at the 25th, 0.14 ± 0.03 at the 50th, 0.24 ± 0.05 at the 75th, and 0.53 ± 0.21 at the 90th percentile. Conclusion Heritability of serum CRP concentration is quantile-specific, which may explain or contribute to the inflated CRP differences between CRP (rs1130864, rs1205, rs1800947, rs2794521, rs3091244), FGB (rs1800787), IL-6 (rs1800795, rs1800796), IL6R (rs8192284), TNF- α (rs1800629) and APOE genotypes following CABG surgery, stroke, TIA, curative esophagectomy, intensive periodontal therapy, or acute exercise; during acute coronary syndrome or Staphylococcus aureus bacteremia; or in patients with chronic rheumatoid arthritis, diabetes, peripheral arterial disease, ankylosing spondylitis, obesity or inflammatory bowel disease or who smoke.

59 BASIC BIOLOGICAL SCIENCES↗

The growth of continents and some consequences since 1.5 Ga

The budget of Earth's oceanic sediment masses was discussed in terms of crustal growth and recycling. Based on estimates of the volume of oceanic sediments and the average age of oceanic crust, a continental denudation rate of 1.65 cu km/yr was computed. This crudely balances estimated crustal production rates of about 1 cu km/yr, but the efficiency of sediment loss via subduction, for example, must be considered. It was argued, on the basis of earthquake focal solutions, imagery of subduction zones, and plate kinematic reconstructions that little, if any, sediment was lost in this way. This yields a present day crustal growth rate of about 1 cu km/yr. The volume of continents to 1.5 Ga ago was discussed, assuming constant continental thickness and freeboard, and a constant hydrosphere volume. It was concluded that ocean ridge length was a factor of about 1.75 greater 1.5 Ga ago, but a major uncertainty is the average spreading rate in the past.

Howell, David G.↗

Case studies in bias reduction and inference for electronic health record data with selection bias and phenotype misclassification

Electronic health records (EHR) are not designed for population‐based research, but they provide easy and quick access to longitudinal health information for a large number of individuals. Many statistical methods have been proposed to account for selection bias, missing data, phenotyping errors, or other problems that arise in EHR data analysis. However, addressing multiple sources of bias simultaneously is challenging. We developed a methodological framework (R package, SAMBA ) for jointly handling both selection bias and phenotype misclassification in the EHR setting that leverages external data sources. These methods assume factors related to selection and misclassification are fully observed, but these factors may be poorly understood and partially observed in practice. As a follow‐up to the methodological work, we demonstrate how to apply these methods for two real‐world case studies, and we evaluate their performance. In both examples, we use individual patient‐level data collected through the University of Michigan Health System and various external population‐based data sources. In case study (a), we explore the impact of these methods on estimated associations between gender and cancer diagnosis. In case study (b), we compare corrected associations between previously identified genetic loci and age‐related macular degeneration with gold standard external summary estimates. These case studies illustrate how to utilize diverse auxiliary information to achieve less biased inference in EHR‐based research.

60 APPLIED LIFE SCIENCES↗