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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 325 records · Page 18

Volumetric Radiosurgery for 1 to 10 Brain Metastases: A Multicenter, Single-Arm, Phase 2 Study

Purpose: Interest is growing in treating multiple brain metastases with radiosurgery. We report on the effectiveness and tolerability of volumetric radiosurgery (VRS). Methods and Materials: We enrolled patients with a ≥6-month estimated life expectancy and 1 to 10 brain metastases with a diameter of ≤3 cm at 5 cancer centers. Volumetric radiosurgery was delivered in 5 fractions with 98% target coverage, prescribed as 95% of 50 Gy (47.5 Gy in 5 fractions) to the metastases with no margin and 95% of 40 Gy (38 Gy in 5 fractions) to their 2-mm planning target volumes, concurrent with 20 Gy to the whole brain planning target volume. The treatment was delivered with daily image guidance using conventional linear accelerators and volumetric modulated arc therapy. A magnetic resonance imaging scan was obtained every 3 months. The primary endpoint was the 3-month objective response in the brain according to the Response Evaluation Criteria in Solid Tumors, version 1.1. The principal secondary endpoint was 1-year actuarial control of treated metastases. Toxicities were graded using the Common Terminology Criteria for Adverse Events, version 4.0. The present study is registered with (ClinicalTrials.gov) ( (clinicaltrials.gov) identifier (NCT01046123)). Results: From July 2010 to May 2013, 60 patients underwent VRS with 47.5 Gy in 5 fractions for 12 metastases in the thalamus and basal ganglia (deep metastases) and 207 non-deep metastases. The median follow-up period was 30.5 months, and the median survival was 10.1 months. For the 43 patients assessable at 3 months, the objective response in the brain was 56%. The treated metastases were controlled in 88% of patients at 1 year and 84% at 3 years. Overall survival did not differ for patients with 4 to 10 versus 1 to 3 metastases (hazard ratio 1.18, P=.6). The crude incidence of severe radionecrosis (grade 3-5) was 25% (3 of 12) per deep metastasis, 1.9% (4 of 219) per non-deep metastasis, and 10% (6 of 60) per patient. Conclusions: For non-deep brain metastases, 47.5 Gy in 5 fractions was tolerable. Volumetric radiosurgery was effective for long-term control of treated brain metastases.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Surgical Resection of Brain Metastases and the Risk of Leptomeningeal Recurrence in Patients Treated With Stereotactic Radiosurgery

Purpose: Recent prospective data have shown that patients with solitary or oligometastatic disease to the brain may be treated with upfront stereotactic radiosurgery (SRS) with deferral of whole-brain radiation therapy (WBRT). This has been extrapolated to the treatment of patients with resected lesions. The aim of this study was to assess the risk of leptomeningeal disease (LMD) in patients treated with SRS to the postsurgical resection cavity for brain metastases compared with patients treated with SRS to intact metastases. Methods and Materials: Four hundred sixty-five patients treated with SRS without upfront WBRT at a single institution were identified; 330 of these with at least 3 months' follow-up were included in this analysis. One hundred twelve patients had undergone surgical resection of at least 1 lesion before SRS compared with 218 treated for intact metastases. Time to LMD and overall survival (OS) time were estimated from date of radiosurgery, and LMD was analyzed by the use of cumulative incidence method with death as a competing risk. Univariate and multivariate analyses were performed with competing risk regression to determine whether various clinical factors predicted for LMD. Results: With a median follow-up time of 9.0 months, 39 patients (12%) experienced LMD at a median of 6.0 months after SRS. At 1 year, the cumulative incidence of LMD, with death as a competing risk, was 5.2% for the patients without surgical resection versus 16.9% for those treated with surgery (Gray test, P<.01). On multivariate analysis, prior surgical resection (P<.01) and breast cancer primary (P=.03) were significant predictors of LMD development. The median OS times for patients undergoing surgery compared with SRS alone were 12.9 and 10.6 months, respectively (log-rank P=.06). Conclusions: In patients undergoing SRS with deferral of upfront WBRT for intracranial metastatic disease, prior surgical resection and breast cancer primary are associated with an increased risk for the development of LMD.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Safety and Efficacy of Radiation Therapy in Advanced Melanoma Patients Treated With Ipilimumab

Purpose: Ipilimumab and radiation therapy (RT) are standard treatments for advanced melanoma; preclinical models suggest the potential for synergy. However, limited clinical information exists regarding safety and optimal timing of the combination. Methods and Materials: We reviewed the records of consecutive patients with unresectable stage 3 or 4 melanoma treated with ipilimumab. Patients were categorized as having received RT or not. Differences were estimated between these 2 cohorts. Results: We identified 88 patients treated with ipilimumab. At baseline, the ipilimumab-plus-RT group (n=44) had more unfavorable characteristics. Despite this, overall survival, progression-free survival, and both immune-related and non–immune-related toxicity were not statistically different (P=.67). Patients who received ipilimumab before RT had an increased duration of irradiated tumor response compared with patients receiving ipilimumab after RT (74.7% vs 44.8% at 12 months; P=.01, log-rank test). In addition, patients receiving ablative RT had non–statistically significantly improved median overall survival (19.6 vs 10.2 months), as well as 6-month (95.1% vs 72.7%) and 12-month (79.7% vs 48.5%) survival rates, compared with those treated with conventionally fractionated RT. Conclusions: We found that both ablative and conventionally fractionated RT can be safely administered with ipilimumab without a clinically apparent increase in toxicity. Patients who received ipilimumab before RT had an increased duration of irradiated tumor response.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Programmatic Comparison and Dissemination of an Audit of Single-fraction Radiation Therapy Prescribing Practices for Bone Metastases is Associated with a Meaningful and Lasting Change in Practice on a Population Level

There is ample evidence that single-fraction radiation therapy (SFRT) is as efficacious as more costly and morbid multifraction regimens. We previously demonstrated that an audit-based intervention increased the use of SFRT in all regional cancer centers the following year. However, other investigators have demonstrated that interventions were only associated with a transient 1-year change in prescribing practices. We sought to determine whether our intervention resulted in a more lasting impact.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Is SABR Cost-Effective in Oligometastatic Cancer? An Economic Analysis of the SABR-COMET Randomized Trial

The phase 2 randomized study SABR-COMET demonstrated that in patients with controlled primary tumors and 1 to 5 oligometastatic lesions, SABR was associated with improved progression-free survival (PFS) compared with standard of care (SoC), but with higher costs and treatment-related toxicities. The aim of this study was to assess the cost-effectiveness of SABR versus SoC in this setting.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Clinicopathologic and Transcriptomic Analysis of Radiation-Induced Lung Injury in Nonhuman Primates

Radiation-induced lung injury (RILI) is a progressive condition with an early phase (radiation pneumonitis) and a late phase (lung fibrosis). RILI may occur after partial-body ionizing radiation exposures or internal radioisotope exposure, with wide individual variability in timing and extent of lung injury. This study aimed to provide new insights into the pathogenesis and progression of RILI in the nonhuman primate (NHP) rhesus macaque model.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

A distinct class of ferredoxin:NADP + oxidoreductase enzymes driving thermophilic ethanol production

Biofuel production from lignocellulosic biomass offers a transformative solution to reduce global fossil fuel dependency. Certain thermophilic anaerobes, including Clostridium thermocellum, show promise for renewable ethanol production due to their ability to break down plant material at high temperatures. However, achieving commercially viable ethanol yields has proven challenging despite extensive engineering efforts. Here, we characterized 27 ferredoxin:NADP + oxidoreductase (Fnor) enzymes for their enzyme activity, nicotinamide cofactor specificity, thermotolerance, and functional expression in C. thermocellum . We identified a subset of 10 of these enzymes as a novel class of Fnor enzymes suited for metabolic pathways aimed at high-titer ethanol production. When expressed in engineered C. thermocellum , these enzymes increased ethanol production up to 2.2-fold. These findings establish a novel ethanol pathway and provide insights into physiological roles and biotechnological applications of this new class of Fnor enzymes.

09 BIOMASS FUELS↗

An extension of the localized artificial diffusivity method for immiscible and high density ratio flows

The localized artificial diffusivity (LAD) method is widely regarded as the preferred multi-material regularization scheme for the compact finite difference method, because it is conservative, easy to implement, and generally robust for a wide range of multi-material problems. However, traditional LAD methods face significant challenges when applied to flows with large density ratios and when maintaining thermodynamic equilibrium across material interfaces. These limitations arise from the formulation of the artificial diffusivity flux and the reliance on enthalpy diffusion for interface regularization. Additionally, traditional LAD methods struggle to ensure stability under large density ratio conditions, fail to maintain a finite interface thickness, and are therefore unsuitable for modeling immiscible interfaces. Here, in this work, we discuss the origins of these issues in traditional LAD methods and propose modifications which enable the simulation of large density ratio and immiscible flows. The proposed method targets the artificial diffusion fluxes at gradients and ringing in the volume fraction, rather than the mass fraction in traditional methods, to consistently regularize large density ratio interfaces. Furthermore, the proposed method introduces an artificial bulk density diffusion term to enforce equilibrium conditions across interfaces. To address the challenge of modeling immiscible flows, a conservative diffuse interface term is incorporated into the formulation to ensure a finite interface thickness. Specific consideration is taken in the design of the method to ensure that these crucial properties are maintained for N -material flows. The effectiveness of the proposed method is demonstrated through a series of canonical test cases, and its accuracy is validated by comparison with experimental data on micro-bubble collapse in water. These results highlight the method’s robustness and its ability to overcome the limitations of traditional LAD approaches.

Artificial diffusivity↗

Radioactive Cesium Isotope Ratios as a Tool for determining Dispersal and Re-dispersal Mechanisms Downwind from the Nevada Nuclear Security Site

Fractionation of the two longer lived radioactive cesium isotopes (135 and 137) produced by above ground nuclear tests have been measured and used to clarify the dispersal mechanisms of cesium deposited in the area between the Nevada Nuclear Security Site (NNSS) and Lake Mead in the southwestern United States. Fractionation of these isotopes is due to the 135 decay chain requiring several days to completely decay to Cs and the 137 decay chain less than one hour. Since the Cs precursors are gases, iodine and xenon, the 135Cs plume was deposited farther downwind than the 137Cs plume. Samples were obtained from the Las Vegas arm of Lake Mead, separated into segments, gamma counted to identify layers of activity and analyzed for 135Cs/137Cs ratios. The layers proved to have nearly identical highly fractionated isotope ratios. This information is consistent with a model where the cesium was initially deposited onto the land area draining into Lake Mead and the composite from all the above ground shots subsequently washed onto the Lake by high intensity rain and windstorms producing a layering of Cs activity where each layer is a portion of the composite.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Mechanical environmental transport of actinides and ¹³⁷Cs from an arid radioactive waste disposal site

Particulate transport represents an important mechanism for actinides and fission products at the Earth's surface; soil samples taken in the early 1970's near the Subsurface Disposal Area (SDA) at Idaho National Laboratory (INL) provide a case study for examining the mechanisms and characteristics of actinide transport under arid conditions. Transuranic waste was disposed via shallow land burial at the SDA until shortly after a flooding event that occurred in 1969. In this study we analyze soils collected in the early 1970's for ¹³⁷Cs, ²⁴¹Am, and Pu using a combination of radiometric and mass spectrometric techniques. Two distinct ²⁴⁰Pu/²³⁹Pu isotopic ratios are observed for contamination from the SDA, with values ranging from at least 0.059 to 0.069. ²⁴¹Am concentrations are observed to increase only slightly in 0-4 cm soils over the ~40 year period since soil sampling, contrary to Markham's previous hypothesis that ²⁴¹Pu is principally associated with the 0-4 cm soil fractions (Markham 1978). The lack of statistical difference in ²⁴¹Am/²³⁹⁺²⁴⁰Pu ratios with depth suggests mechanical transport and mixing discrete contaminated particles under arid conditions. Occasional samples beyond the northeastern corner are observed to contain anomalously high Pu concentrations with corresponding low ²⁴⁰Pu/²³⁹Pu atoms ratios, suggesting the occurrence of "hot particles;" application of a background Pu subtraction results in calculated Pu atom ratios for the "hot particles" which are statistically similar to those observed in the northeastern corner. Taken together, our data suggests that flooding resulted in mechanical transport of contaminated particles into the area between the SDA and the flood containment dike in the northeastern corner, following which subsequent contamination spreading resulted from wind transport of discrete particles.

54 ENVIRONMENTAL SCIENCES↗

The Structure of the Biofilm-controlling Response Regulator BfmR from Acinetobacter baumannii Reveals Details of Its DNA-binding Mechanism

The rise of drug-resistant bacterial infections coupled with decreasing antibiotic efficacy poses a significant challenge to global health care. Acinetobacter baumannii is an insidious, emerging bacterial pathogen responsible for severe nosocomial infections aided by its ability to form biofilms. The response regulator BfmR, from the BfmR/S two-component system, is the master regulator of biofilm initiation in A. baumannii and is a tractable therapeutic target. Here we present the structure of A. baumannii BfmR using a hybrid approach combining X-ray crystallography, nuclear magnetic resonance spectroscopy, chemical crosslinking mass spectrometry, and molecular modeling. We also show that BfmR binds the previously proposed bfmRS promoter sequence with moderate affinity. We report that while BfmR shares many traits with other OmpR/PhoB family response regulators, some unusual properties were observed. Most importantly, we observe that when phosphorylated, BfmR binds this promoter sequence with a lower affinity than when not phosphorylated. All other OmpR/PhoB family members studied to date show an increase in DNA-binding affinity upon phosphorylation. Understanding the structural and biochemical mecha

59 BASIC BIOLOGICAL SCIENCES↗

Hole traps in sodium silicate: First-principles calculations of the mobility edge

Here, the structure and properties of (Na 2 O) 0.30 (SiO 2 ) 0.70 sodium silicate glass are studied by combined ab-initio and classical molecular dynamics simulations to identify the sources of electronic traps in the band gap. Structures from classical molecular dynamics melt-quench simulations are taken as initial configurations for first-principles density functional theory structural relaxation, from which electronic properties are determined. An ensemble of thirty glass structures, each containing 660 atoms, is prepared in order to perform statistical analyses. The inverse participation ratio is used as a metric to characterize localized states in the band gap and determine the mobility edge. Structures with varying amounts of local disorder (traps) are compared. The most localized and highest energy trap states are due to Si atoms with 2–3 non-bridging oxygen atoms. Control of the electronic properties of amorphous insulators and semiconductors is essential for the advancement of many technologies, such as photovoltaics and scintillators, for which the present analysis is indispensable.

36 MATERIALS SCIENCE↗