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At least 1,279 records · Page 71

SU-C-BRD-04: Comparison of Shallow Fluence to Deep Point Dose Measurements for Spine VMAT SBRT Patient-Specific QA

Purpose: To investigate the sensitivity of traditional gamma-index-based fluence measurements for patient-specific measurements in VMAT delivered spine SBRT. Methods: The ten most recent cases for spine SBRT were selected. All cases were planned with Eclipse RapidArc for a TrueBeam STx. The delivery was verified using a point dose measurement with a Pinpoint 3D micro-ion chamber in a Standard Imaging Stereotactic Dose Verification Phantom. Two points were selected for each case, one within the target in a low dose-gradient region and one in the spinal cord. Measurements were localized using on-board CBCT. Cumulative and separate arc measurements were acquired with the ArcCheck and assessed using the SNC patient software with a 3%/3mm and 2%/2mm gamma analysis with global normalization and a 10% dose threshold. Correlations between data were determined using the Pearson Product-Moment Correlation. Results: For our cohort of patients, the measured doses were higher than calculated ranging from 2.2%–9.7% for the target and 1.0%–8.2% for the spinal cord. There was strong correlation between 3%/3mm and 2%/2mm passing rates (r=0.91). Moderate correlation was found between target and cord dose with a weak fit (r=0.67, R-Square=0.45). The cumulative ArcCheck measurements showed poor correlation with the measured point doses for both the target and cord (r=0.20, r=0.35). If the arcs are assessed separately with an acceptance criteria applied to the minimum passing rate between all arcs, a moderate negative correlation was found for the target and cord (r=−0.48, r= −0.71). The case with the highest dose difference (9.7%) received a passing rate of 97.2% for the cumulative arcs and 87.8% for the minimum with separate arcs. Conclusion: Our data suggest that traditional passing criteria using ArcCheck with cumulative measurements do not correlate well with dose errors. Separate arc analysis shows better correlation but may still miss large dose errors. Point dose verifications are recommended.

60 APPLIED LIFE SCIENCES↗

SU-G-TeP2-12: IROCHouston and MDAPL SRS Anthropomorphic Phantom Results

Purpose: To report the results of SRS phantom irradiations Methods: Anthropomorphic SRS head phantoms were sent to institutions participating in NCI sponsored SRS clinical trials and institutions interested in verifying SRS treatment delivery. The phantom shell was purchased from Phantom Laboratory and altered to house dosimetry and imaging inserts. The imaging insert has 1.9 cm diameter spherical target. The dosimetry insert holds two TLD capsules and radiochromic film in the coronal and sagittal planes through the center of the target. Institutions were asked to image, plan and treat the phantom as they would an SRS patient. GammaKnife, CyberKnife and c-arm accelerator institutions were asked to cover the target with 15 Gy, 20 Gy and 25 Gy, respectively. Following these guidelines and typical planning protocols for these three types of machines gives roughly 30 Gy to the center of the target for all units. Submission of the DICOM digital data set was required for analysis. Criteria of 5% for TLD results and 85% of pixels passing 5%/3mm gamma analysis were applied beginning in 2013. Results: The phantom was analyzed 269 times between the beginning of 2013 to present. The pass rate is 81%. Nineteen of the irradiation results failed only the TLD criteria, 19 failed only the film criteria and 12 failed both. Irradiations included 32 CyberKnife 23 GammaKnife, 3 TomoTherapy and 211 c-arm units. Planning systems included Eclipse, Ergo, GammaPlan, Hi-Art, iPlan, Monaco, MultiPlan, Pinnacle, RayStation, XiO and XKnife. Irradiations that were not accompanied with DICOM data were not included in this analysis. Conclusion: The phantom is a valuable end-to-end test used to independently verify the accuracy of SRS treatment delivery. This investigation was supported by IROC grant CA180803 awarded by the NCI.

60 APPLIED LIFE SCIENCES↗

Assessing United States County-Level Exposure for Research on Tropical Cyclones and Human Health

Tropical cyclone epidemiology can be advanced through exposure assessment methods that are comprehensive and consistent across space and time, as these facilitate multiyear, multistorm studies. Further, an understanding of patterns in and between exposure metrics that are based on specific hazards of the storm can help in designing tropical cyclone epidemiological research. a) Provide an open-source data set for tropical cyclone exposure assessment for epidemiological research; and b) investigate patterns and agreement between county-level assessments of tropical cyclone exposure based on different storm hazards. We created an open-source data set with data at the county level on exposure to four tropical cyclone hazards: peak sustained wind, rainfall, flooding, and tornadoes. The data cover all eastern U.S. counties for all land-falling or near-land Atlantic basin storms, covering 1996–2011 for all metrics and up to 1988–2018 for specific metrics. We validated measurements against other data sources and investigated patterns and agreement among binary exposure classifications based on these metrics, as well as compared them to use of distance from the storm’s track, which has been used as a proxy for exposure in some epidemiological studies. Our open-source data set was typically consistent with data from other sources, and we present and discuss areas of disagreement and other caveats. Over the study period and area, tropical cyclones typically brought different hazards to different counties. Therefore, when comparing exposure assessment between different hazard-specific metrics, agreement was usually low, as it also was when comparing exposure assessment based on a distance-based proxy measurement and any of the hazard-specific metrics. Our results provide a multihazard data set that can be leveraged for epidemiological research on tropical cyclones, as well as insights that can inform the design and analysis for tropical cyclone epidemiological research.

60 APPLIED LIFE SCIENCES↗

Computational Ranking of Yerba Mate Small Molecules Based on Their Predicted Contribution to Antibacterial Activity against Methicillin-Resistant Staphylococcus aureus

We report that the aqueous extract of yerba mate, a South American tea beverage made from Ilex paraguariensis leaves, has demonstrated bactericidal and inhibitory activity against bacterial pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). The gas chromatography-mass spectrometry (GC-MS) analysis of two unique fractions of yerba mate aqueous extract revealed 8 identifiable small molecules in those fractions with antimicrobial activity. For a more comprehensive analysis, a data analysis pipeline was assembled to prioritize compounds for antimicrobial testing against both MRSA and methicillin-sensitive S. aureus using forty-two unique fractions of the tea extract that were generated in duplicate, assayed for activity, and analyzed with GC-MS. As validation of our automated analysis, we checked our predicted active compounds for activity in literature references and used authentic standards to test for antimicrobial activity. 3,4-dihydroxybenzaldehyde showed the most antibacterial activity against MRSA at low concentrations in our bioassays. In addition, quinic acid and quercetin were identified using random forests analysis and 5-hydroxy pipecolic acid was identified using linear discriminant analysis. We also generated a ranked list of unidentified compounds that may contribute to the antimicrobial activity of yerba mate against MRSA. Here we utilized GC-MS data to implement an automated analysis that resulted in a ranked list of compounds that likely contribute to the antimicrobial activity of aqueous yerba mate extract against MRSA.

59 BASIC BIOLOGICAL SCIENCES↗

The Geologic History of Mars: An Astrobiology Perspective

Fourteen SNC meteorites contain information which must be incorporated with recent spaceflight data for developing Mars' geologic history. SNCs have crystallization ages of 4500 to 160 m.y. Tle oldest meteorite ALH84001 contains information on the Noachian period of Mars' history. There are no meteorites from the Hesperian period and the remaining 13 meteorites fall into two age groups within the Amazonian: The nakhlites around 1300 m.y. and the shergottites between 800-160 m.y. Oxygen isotopic analysis of Martian samples shows two distinct O2 reservoirs throughout Martian history indicating late additions of volatiles and a lack of plate tectonics prior to 3.9 Gy. Evidence for percolation of aqueous brines through impact-produced fractures in the rocky surface is contained in the 3.9 Gy-old ALH84001 carbonate deposits. These carbonates precipitated at approx. 100 C. At this time life had already evolved on Earth. Early Mars could have hosted life similar to the bacteria that inhabited early Earth. Potential microorganisms could have been transported into fractures by carbonate-bearing waters and their remains could have become incorporated into the precipitated carbonate. Since Mars had a weak magnetic field at this time, it can be hypothesized that some of the Martian microorganisms may have been similar to terrestrial magnetotactic bacteria. Over geologic time episodic cratering, and tectonic events have occurred on Mars along with the periodic release of subsurface waters which may have produced clays within SNC meteorites. The geochemical data contained within SNC meteorites complements previous observational data and the recent Mars Global Surveyor data to provide a geological and environmental history which spans almost the entire lifespan on Mars. One of the outstanding features of this model is the possible creation of an early (about 4 Gy) volatile reservoir distinct from the outgassed Mars volatiles, and the persistence of this reservoir throughout most, if not all of subsequent Mars' history. Within the framework of this history a potential scenario for a possible record of living organisms is provided by suggestive structures and organic signatures trapped within secondary mineral deposits and alteration features of some SNC meteorites. Tracing the differences in oxygen isotopic compositions within Martian components allows us to gain insight in the history of Mars.

Gibson, Everett K.↗

RNA helicase MOV10 functions as a co-factor of HIV-1 Rev to facilitate Rev/RRE-dependent nuclear export of viral mRNAs

Human immunodeficiency virus type 1 (HIV-1) exploits multiple host factors during its replication. The REV/RRE-dependent nuclear export of unspliced/partially spliced viral transcripts needs the assistance of host proteins. Recent studies have shown that MOV10 overexpression inhibited HIV-1 replication at various steps. However, the endogenous MOV10 was required in certain step(s) of HIV-1 replication. In this report, we found that MOV10 potently enhances the nuclear export of viral mRNAs and subsequently increases the expression of Gag protein and other late products through affecting the Rev/RRE axis. The co-immunoprecipitation analysis indicated that MOV10 interacts with Rev in an RNA-independent manner. The DEAG-box of MOV10 was required for the enhancement of Rev/RRE-dependent nuclear export and the DEAG-box mutant showed a dominant-negative activity. Our data propose that HIV-1 utilizes the anti-viral factor MOV10 to function as a co-factor of Rev and demonstrate the complicated effects of MOV10 on HIV-1 life cycle. - Highlights: • MOV10 can function as a co-factor of HIV-1 Rev. • MOV10 facilitates Rev/RRE-dependent transport of viral mRNAs. • MOV10 interacts with Rev in an RNA-independent manner. • The DEAG-box of MOV10 is required for the enhancement of Rev/RRE-dependent export.

60 APPLIED LIFE SCIENCES↗

Nutri‐cereal tissue‐specific transcriptome atlas during development: Functional integration of gene expression to identify mineral uptake pathways in little millet ( Panicum sumatrense )

SUMMARY Little millet (Panicum sumatrenseRoth ex Roem. & Schult.) is an essential minor millet of southeast Asia and Africa's temperate and subtropical regions. The plant is stress‐tolerant, has a short life cycle, and has a mineral‐rich nutritional profile associated with unique health benefits. We report the developmental gene expression atlas of little millet (genotype JK‐8) from ten tissues representing different stages of its life cycle, starting from seed germination and vegetative growth to panicle maturation. The developmental transcriptome atlas led to the identification of 342 827 transcripts. The BUSCO analysis and comparison with the transcriptomes of related species confirm that this study presents high‐quality, in‐depth coverage of the little millet transcriptome. In addition, the eFP browser generated here has a user‐friendly interface, allowing interactive visualizations of tissue‐specific gene expression. Using these data, we identified transcripts, the orthologs of which inArabidopsisand rice are involved in nutrient acquisition, transport, and response pathways. The comparative analysis of the expression levels of these transcripts holds great potential for enhancing the mineral content in crops, particularly zinc and iron, to address the issue of “hidden hunger” and to attain nutritional security, making it a valuable asset for translational research.

Plant Sciences↗

ECAR-2925 AGC-2 Specimen Load Calculations by Stack

This Engineering Calculations Analysis Report (ECAR) documents the results of the summarization of the load cell data taken during the Advance Test Reactor (ATR) during Cycles 149A, 149B, 150A, 150B, 151A, 151B, and 152A. During each cycle, the specimens in the upper portion of the experiment (Stacks 1–6) were subjected to a compressive load. The applied load of each stack was monitored using six different load cells. Collecting data detailing the loads applied over the life of the experiment is necessary for use in future analyses. This load summary data will be used in creep rate estimations and post-irradiated examination (PIE) of material properties

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Orbit transfer rocket engine technology program. Phase 2: Advanced engine study

In Phase 2 of the Advanced Engine Study, the Failure Modes and Effects Analysis (FMEA) maintenance-driven engine design, preliminary maintenance plan, and concept for space operable disconnects generated in Phase 1 were further developed. Based on the results of the vehicle contractors Orbit Transfer Vehicle (OTV) Concept Definition and System Analysis Phase A studies, minor revisions to the engine design were made. Additional refinements in the engine design were identified through further engine concept studies. These included an updated engine balance incorporating experimental heat transfer data from the Enhanced Heat Load Thrust Chamber Study and a Rao optimum nozzle contour. The preliminary maintenance plan of Phase 1 was further developed through additional studies. These included a compilation of critical component lives and life limiters and a review of the Space Shuttle Main Engine (SSME) operations and maintenance manual in order to begin outlining the overall maintenance procedures for the Orbit Transfer Vehicle Engine and identifying technology requirements for streamlining space-based operations. Phase 2 efforts also provided further definition to the advanced fluid coupling devices including the selection and preliminary design of a preferred concept and a preliminary test plan for its further development.

Erickson, C.↗

Structural risk assessment and aircraft fleet maintenance

In the present analysis, deterministic flaw growth analysis is used to project the failure distributions from inspection data. Inspection data is reported for each critical point in the aircraft. The data will indicate either a crack of a specific size or no crack. The crack length may be either less than, equal to, or greater than critical size for that location. Non-critical length cracks are projected to failure using the crack growth characteristics for that location to find the life when it will be at critical length. Greater-than-critical length cracks are projected back to determine the life at failure, that is, when it was at critical length. The same process is used as in the case of a non-critical crack except that the projection goes the other direction. These points, along with the critical length cracks are used to determine the failure distribution. To be able to use data from different aircraft to build a common failure distribution, a consistent life variable must be used. Aircraft life varies with the severity of the usage; therefore the number of flight hours for a particular aircraft must be modified by its usage factor to obtain a normalized life which can be compared with that from other aircraft.

Smith, Herb, Jr.↗

Hydrogen effects on low-cycle fatigue of the single-crystal nickel-base superalloy CMSX-2

The effects of hydrogen on the low-cycle fatigue behavior of CMSX-2 (001)-oriented single crystals were examined. Fatigue tests were conducted under constant plastic strain amplitude control. Cyclic stress-strain curves and fatigue life data at different plastic strain amplitudes were determined for hydrogen-free and hydrogen-charged specimens. Two charging procedures, leading to different hydrogen concentrations, were applied. Hydrogen was found to decrease significantly the number of cycles to failure under the various experimental conditions. The increasing hydrogen concentration and ratio of the hydrogen to nonhydrogen-containing volume were found to shorten fatigue life in hydrogen-charged specimens. Based on the analysis of cyclic stress-strain curves and optical and transmission electron microscopy, it was established that hydrogen enhanced strain localization and promoted crystallographic stage I cracking, leading to embrittlement.

Dollar, M.↗

Characteristics of Post-Sorbent and High Temperature Catalytic Oxidizer Beds After Long-Term On-Orbit Use

Trace contaminants are produced on-orbit by human metabolic processes and equipment off-gassing. These potentially hazardous contaminants are removed by the Trace Contaminant Control Subassembly (TCCS) in the US segment of the International Space Station (ISS). The TCCS has been operating since February 2001. Analysis of on-orbit telemetry data indicated a slow increase in the TCCS system flow resistance over the five years of operation. Two of the packed beds within the TCCS were replaced to return the TCCS to its nominal operation conditions; the high temperature catalytic oxidizer and the post-sorbent bed. Results from the examination of the returned beds are presented along with a discussion about changes to bed service life.

Johnson, Sharon↗

Characterizing the 2019-2021 Drought in La Plata River Basin With GLDAS and SMAP

Study region The La Plata River Basin (LPRB) is an area of interest, as there was a significant drought event from 2019 to 2021. With the LPRB being the second largest river basin in South America, this drought affected all aspects of life for over 100 million people who inhabit this area. Study focus In this study, we utilized satellite and model datasets to examine spatial and temporal variability of hydrological anomalies throughout the basin before and during the drought event. These variable anomalies, such as precipitation and groundwater, are derived from the Global Land Data Assimilation System (GLDAS). Additionally, the Soil Moisture Active Passive (SMAP) observations were used in the spatial and temporal analysis of the drought. The water loss was calculated using the Mann-Kendall test to assess the changes in anomalies for the terrestrial water storage throughout the basin and subbasins. New hydrological insights for the region The main insight from this study is the agreement of the GLDAS anomalies with the SMAP data throughout the drought. The variable anomalies all decreased and showed alignment with the downscaled 1 km SMAP which shows alignment with the trends from in-situ observations. It was also found that the Upper Parana subbasin lost the most water over the drought period. These products improve understanding of the spatial variability within the entire basin and facilitate understanding of droughts and resources to assist in the future management of water resources.

La Plata Basin↗

Analysis of Patient-Reported Outcome Utilization Within National Clinical Trials Network Cooperative Group Radiation Oncology Trials Over the Past 2 Decades

When treating cancer, both quantity and quality of life are valuable, though oncology trials have long placed greater emphasis on the former. The goal of this work was to evaluate how patient-reported outcomes (PROs) have been incorporated into radiation therapy trials within the National Clinical Trials Network over the last 2 decades to measure quality of life and to assess how PRO data have been disseminated in publications upon trial conclusion.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Bayesian network ensemble as a multivariate strategy to predict radiation pneumonitis risk

Purpose: Prediction of radiation pneumonitis (RP) has been shown to be challenging due to the involvement of a variety of factors including dose–volume metrics and radiosensitivity biomarkers. Some of these factors are highly correlated and might affect prediction results when combined. Bayesian network (BN) provides a probabilistic framework to represent variable dependencies in a directed acyclic graph. The aim of this study is to integrate the BN framework and a systems’ biology approach to detect possible interactions among RP risk factors and exploit these relationships to enhance both the understanding and prediction of RP. Methods: The authors studied 54 nonsmall-cell lung cancer patients who received curative 3D-conformal radiotherapy. Nineteen RP events were observed (common toxicity criteria for adverse events grade 2 or higher). Serum concentration of the following four candidate biomarkers were measured at baseline and midtreatment: alpha-2-macroglobulin, angiotensin converting enzyme (ACE), transforming growth factor, interleukin-6. Dose-volumetric and clinical parameters were also included as covariates. Feature selection was performed using a Markov blanket approach based on the Koller–Sahami filter. The Markov chain Monte Carlo technique estimated the posterior distribution of BN graphs built from the observed data of the selected variables and causality constraints. RP probability was estimated using a limited number of high posterior graphs (ensemble) and was averaged for the final RP estimate using Bayes’ rule. A resampling method based on bootstrapping was applied to model training and validation in order to control under- and overfit pitfalls. Results: RP prediction power of the BN ensemble approach reached its optimum at a size of 200. The optimized performance of the BN model recorded an area under the receiver operating characteristic curve (AUC) of 0.83, which was significantly higher than multivariate logistic regression (0.77), mean heart dose (0.69), and a pre-to-midtreatment change in ACE (0.66). When RP prediction was made only with pretreatment information, the AUC ranged from 0.76 to 0.81 depending on the ensemble size. Bootstrap validation of graph features in the ensemble quantified confidence of association between variables in the graphs where ten interactions were statistically significant. Conclusions: The presented BN methodology provides the flexibility to model hierarchical interactions between RP covariates, which is applied to probabilistic inference on RP. The authors’ preliminary results demonstrate that such framework combined with an ensemble method can possibly improve prediction of RP under real-life clinical circumstances such as missing data or treatment plan adaptation.

60 APPLIED LIFE SCIENCES↗

Transcript abundance on its own cannot be used to infer fluxes in central metabolism

An attempt has been made to define the extent to which metabolic flux in central plant metabolism is reflected by changes in the transcriptome and metabolome, based on an analysis of in vitro cultured immature embryos of two oilseed rape (Brassica napus) accessions which contrast for seed lipid accumulation. Metabolic flux analysis (MFA) was used to constrain a flux balance metabolic model which included 671 biochemical and transport reactions within the central metabolism. This highly confident flux information was eventually used for comparative analysis of flux vs. transcript (metabolite). Metabolite profiling succeeded in identifying 79 intermediates within the central metabolism, some of which differed quantitatively between the two accessions and displayed a significant shift corresponding to flux. An RNA-Seq based transcriptome analysis revealed a large number of genes which were differentially transcribed in the two accessions, including some enzymes/proteins active in major metabolic pathways. With a few exceptions, differential activity in the major pathways (glycolysis, TCA cycle, amino acid, and fatty acid synthesis) was not reflected in contrasting abundances of the relevant transcripts. The conclusion was that transcript abundance on its own cannot be used to infer metabolic activity/fluxes in central plant metabolism. Lastly, this limitation needs to be borne in mind in evaluating transcriptome data and designing metabolic engineering experiments.

13C-metabolic flux analysis↗

A Multivariate Dynamic Spatial Factor Model for Speciated Pollutants and Adverse Birth Outcomes

Evidence suggests that exposure to elevated concentrations of air pollution during pregnancy is associated with increased risks of birth defects and other adverse birth outcomes. While current regulations put limits on total PM2.5 concentrations, there are many speciated pollutants within this size class that likely have distinct effects on perinatal health. However, due to correlations between these speciated pollutants, it can be difficult to decipher their effects in a model for birth outcomes. To combat this difficulty, we develop a multivariate spatio-temporal Bayesian model for speciated particulate matter using dynamic spatial factors. These spatial factors can then be interpolated to the pregnant women’s homes to be used to model birth defects. The birth defect model allows the impact of pollutants to vary across different weeks of the pregnancy in order to identify susceptible periods. Here, the proposed methodology is illustrated using pollutant monitoring data from the Environmental Protection Agency and birth records from the National Birth Defect Prevention Study.

54 ENVIRONMENTAL SCIENCES↗

Nation-Scale Adoption of Shorter Breast Radiation Therapy Schedules Can Increase Survival in Resource Constrained Economies: Results From a Markov Chain Analysis

Purpose: Hypofractionated whole breast irradiation and accelerated partial breast irradiation (APBI) offer women options for shorter courses of breast radiation therapy. The impact of these shorter schedules on the breast cancer populations of emerging economies with limited radiation therapy resources is unknown. We hypothesized that adoption of these schedules would improve throughput in the system and, by allowing more women access to life-saving treatments, improve patient survival within the system. Methods and Materials: We designed a Markov chain model to simulate the different health states that a postlumpectomy or postmastectomy patient could enter over the course of a 20-year follow-up period. Transition rates between health states were adapted from published data on recurrence rates. We used primary data from a tertiary care hospital in Lahore, Pakistan, to populate the model with proportional use of mastectomy versus breast conservation and to estimate the proportion of patients suitable for APBI. Sensitivity analyses on the use of APBI and relative efficacy of APBI were conducted to study the impact on the population. Results: The shorter schedule resulted in more women alive and more women remaining without evidence of disease (NED) compared with the conventional schedule, with an absolute difference of about 4% and 7% at 15 years, respectively. Among women who had lumpectomies, the chance of remaining alive and with an intact breast was 62% in the hypofractionation model and 54% in the conventional fractionation model. Conclusions: Increasing throughput in the system can result in improved survival, improved chances of remaining without evidence of disease, and improved chances of remaining alive with a breast. These findings are significant and suggest that adoption of hypofractionation in emerging economies is not simply a question of efficiency and cost but one of access to care and patient survivorship.

62 RADIOLOGY AND NUCLEAR MEDICINE↗