Scoping evaluation of trace isotopic ratios within the noble metal-phase as indicators of reactor class
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Purpose: To determine the maximally tolerated dose of sorafenib delivered before, during, and after stereotactic body radiation therapy (SBRT) in hepatocellular carinoma (HCC). Methods and Materials: Eligible patients had locally advanced Child-Pugh class A HCC, showed Eastern Cooperative Oncology Group performance status 0-1, and were ineligible for standard local-regional therapies. Sorafenib was dose escalated in 2 strata: (1) low effective irradiated liver volume (veff) < 30% and (2) high veff 30%to 60%. Sorafenib (400 mg daily = dose level 1) was administered for 12 weeks, with 6 fractions SBRT delivered weeks 2 and 3, and escalation to full dose (400 mg twice daily) after 12 weeks as tolerated. Standard 3 + 3 cohorts with dose escalation of sorafenib were planned. Results: Sixteen patients (4 low veff, median dose 51 Gy; 12 high veff, median dose 33 Gy) were treated at 2 sorafenib dose levels. Of those patients 75% were had Barcelona Clinic Liver Cancer stage C, and 63% had main branch portal vein invasion. In the low veff stratum, no dose-limiting toxicities (DLTs) were observed in 4 patients treated with SBRT and sorafenib 400 mg. Inb the high veff stratum: 2 of 3 evaluable patients treated with sorafenib 400 mg experienced DLT (grade 3 large bowel bleed and grade 4 bowel obstruction 51 and 27 days, respectively, after SBRT). One of 6 evaluable patients at dose level −1 (200 mg once daily) experienced a grade 3 tumor rupture at week 5. Median overall survival and in-field local progression have not been reached. Worsening of Child-Pugh liver function class was seen in 6 of 12 patients in the high veff stratum. Conclusions: Significant toxicity was observed in the high veff stratum, and concurrent SBRT with sorafenib is not recommended outside a clinical trial.
The emergence of the multi-core era has led to increased interest in designing effective yet practical parallel programming models. Models based on task graphs that operate on single-assignment data are attractive in several ways: they can support dynamic applications and precisely represent the available concurrency. However, they also require nuanced algorithms for scheduling and memory management for efficient execution. In this paper, we consider memory-efficient dynamic scheduling of task graphs. Specifically, we present a novel approach for dynamically recycling the memory locations assigned to data items as they are produced by tasks. We develop algorithms to identify memory-efficient store recycling functions by systematically evaluating the validity of a set of (user-provided or automatically generated) alternatives. Because recycling function can be input data-dependent, we have also developed support for continued correct execution of a task graph in the presence of a potentially incorrect store recycling function. Experimental evaluation demonstrates that our approach to automatic store recycling incurs little to no overheads, achieves memory usage comparable to the best manually derived solutions, often produces recycling functions valid across problem sizes and input parameters, and efficiently recovers from an incorrect choice of store recycling functions.
Injection of acidic hydraulic fracture fluid (HFF) into shale formations for unconventional oil/gas production results in chemical reactions in the shale matrix that can alter fluid transport. Here, we report the results of set of experiments designed to evaluate the impact of calcite dissolution as a function of carbonate mineral content on matrix chemical reactivity and pore-space modification concomitant with imbibition. In this study, we tracked acidic HFF transport in four samples of Wolfcamp shale with calcite contents varying from 4% to 59% by monitoring the rate and spatial extent of bromide tracer transport using synchrotron-based X-ray fluorescence microprobe (XFM) imaging. Concurrently, we also carried out XFM imaging of the spatial distribution of Ca in the Wolfcamp shale cores (as a proxy of calcite distribution). Our approach thus yields a direct record of time-resolved selective ion transport resulting from the penetration of acidic HFF and the associated mineral transformations in the shale cores. We show that the variability in calcite content of Wolfcamp shale samples can directly affect the rate and spatial extent of imbibition. Although reaction of the acidic HFF with carbonates in shales enhances calcite dissolution and increases porosity, the spatial extent of calcite dissolution in the shale matrix is limited due to a rapid neutralization of pH. The relative abundance and spatial distribution of calcite control the chemical saturation state of the HFF progressing into the matrix. As a result, calcite has a major impact on the spatial extent and rate of matrix alteration and thus on HFF transport during subsurface reservoir stimulation. Consequently, increased calcite content in the shale matrix inhibits the spatial extent of the pore-volume increase and, by extension, the spatial extent and rate of imbibition. Our results thus show that the overall rates of calcite dissolution approach the rates of acidic HFF transport (i.e., Damköhler number ~1), which could contribute to the efficiency of subsurface reservoir stimulation. A better understanding of HFF-calcite reaction rates is crucial for improving the prediction and optimization of fluid transport across HFF-shale interfaces during hydraulic fracturing.
Members of the order Methanomicrobiales are abundant, and sometimes dominant, hydrogenotrophic (H 2 -CO 2 utilizing) methanoarchaea in a broad range of anoxic habitats. In spite of their key roles in greenhouse gas emissions and waste conversion to methane, little is known about the physiological and genomic bases for their widespread distribution and abundance. In this work, we compared the genomes of nine diverse Methanomicrobiales strains, examined their pangenomes, reconstructed gene flow and identified genes putatively mediating their success across different habitats. Most strains slowly increased gene content whereas one, Methanocorpusculum labreanum, evidenced genome downsizing. Peat-dwelling Methanomicrobiales showed adaptations centered on improved transport of scarce inorganic nutrients and likely use H + rather than Na + transmembrane chemiosmotic gradients during energy conservation. In contrast, other Methanomicrobiales show the potential to concurrently use Na + and H + chemiosmotic gradients. Analyses also revealed that the Methanomicrobiales lack a canonical electron bifurcation system (MvhABGD) known to produce low potential electrons in other orders of hydrogenotrophic methanogens. Additional putative differences in anabolic metabolism suggest that the dynamics of interspecies electron transfer from Methanomicrobiales syntrophic partners can also differ considerably. Altogether, our findings suggest profound differences in electron trafficking in the Methanomicrobiales compared with other hydrogenotrophs, and warrant further functional evaluations.
As supercomputers advance towards exascale capabilities, computational intensity increases significantly, and the volume of data requiring storage and transmission experiences exponential growth. Adaptive Mesh Refinement (AMR) has emerged as an effective solution to address these two challenges. Concurrently, error-bounded lossy compression is recognized as one of the most efficient approaches to tackle the latter issue. Despite their respective advantages, few attempts have been made to investigate how AMR and error-bounded lossy compression can function together. To this end, this study presents a novel in-situ lossy compression framework that employs the HDF5 filter to improve both I/O costs and boost compression quality for AMR applications. We implement our solution into the AMReX framework and evaluate on two real-world AMR applications, Nyx and WarpX, on the Summit supercomputer. Experiments with 512 cores demonstrate that AMRIC improves the compression ratio by 81X and the I/O performance by 39X over AMReX's original compression solution.
Drought and high-severity, stand-replacing wildfires can have substantial impacts on the composition of avian communities, including stop-over communities during migration. An inextricable link exists between drought and wildfire, each operating and impacting across different timescales. Many studies have found nonlinear avian abundance trends in breeding community time series data that include pre- and post-fire observations, describing an initial decrease in abundance followed by rapid increases that can attenuate over time. Here, we use a fall bird-banding dataset to evaluate shifts in a drought-impacted avian community following wildfire from taxonomic, functional, and phylogenetic perspectives. We looked at the community as a whole and also categorized birds as residents, migrants, and breeders to assess potential varying responses at the study site. We observed post-fire shifts in functional and phylogenetic diversity that corresponded to changes in vegetation. An influx of migratory insectivores post-fire drove much of the variation between pre- and post-fire avian communities and toward a more related, less phylogenetically dispersed community. A concurrent monsoon season drought was also associated with functional and phylogenetic diversity, highlighting the intertwined pulse press effects on avian communities. Overall, our results suggest that, although bird communities are immediately impacted by fire-driven resource changes, they can rebound over time, it is unclear how long-term drought may continue to shape the composition of these avian communities.
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Salt formations are one of the potential host rocks for the final disposal of high-level radioactive waste (HLW) in deep geological repositories, both in Germany and the United States. The safe isolation of radioactive waste in these repositories relies on a multi-barrier system, combining engineered and natural barriers. The natural barrier is provided by the salt rock itself, known for its self-sealing properties and long-term stability. The engineered barrier, on the other hand, comprises sealing components strategically placed within the repository to enhance its containment capabilities. In both Germany and the United States, long-term safety assessments require demonstrating the integrity of the natural barrier for a period of up to 1 million years. Concurrently, the engineered barrier system (EBS) must maintain its structural and functional integrity until the long-term sealing, such as the granular salt backfill material, has re-consolidated to its final low porosity and permeability. Based on extensive expertise and experience with engineered barriers in salt formations, BGE TECHNOLOGY GmbH and Sandia National Laboratories have partnered to develop a robust methodology for the integrity and performance assessment of EBS in HLW repositories through the RANGERS project. This collaborative effort aims to establish a unified approach to geotechnical engineering, repository design, integrity and performance evaluation of EBS in salt repositories.
Purpose: Virtually all patients with malignant glioma (MG) eventually recur. This study evaluates the safety of concurrent stereotactic radiosurgery (SRS) and bevacizumab (BVZ), an antiangiogenic agent, in treatment of recurrent MG. Methods and Materials: Fifteen patients with recurrent MG, treated at initial diagnosis with surgery and adjuvant radiation therapy/temozolomide and then at least 1 salvage chemotherapy regimen, were enrolled in this prospective trial. Lesions <3 cm in diameter were treated in a single fraction, whereas those 3 to 5 cm in diameter received 5 5-Gy fractions. BVZ was administered immediately before SRS and 2 weeks later. Neurocognitive testing (Mini-Mental Status Exam, Trail Making Test A/B), Functional Assessment of Cancer Therapy-Brain (FACT-Br) quality-of-life assessment, physical exam, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) were performed immediately before SRS and 1 week and 2 months following completion of SRS. The primary endpoint was central nervous system (CNS) toxicity. Secondary endpoints included survival, quality of life, microvascular properties as measured by DCE-MRI, steroid usage, and performance status. Results: One grade 3 (severe headache) and 2 grade 2 CNS toxicities were observed. No patients experienced grade 4 to 5 toxicity or intracranial hemorrhage. Neurocognition, quality of life, and Karnofsky performance status did not change significantly with treatment. DCE-MRI results suggest a significant decline in tumor perfusion and permeability 1 week after SRS and further decline by 2 months. Conclusions: Treatment of recurrent MG with concurrent SRS and BVZ was not associated with excessive toxicity in this prospective trial. A randomized trial of concurrent SRS/BVZ versus conventional salvage therapy is needed to establish the efficacy of this approach.
Background: Semiquantitative methods such as the standardized uptake value ratio (SUVR) require normalization of the radiotracer activity to a reference tissue to monitor changes in the accumulation of amyloid-β (Aβ) plaques measured with positron emission tomography (PET). The objective of this study was to evaluate the effect of reference tissue normalization in a test–retest 18F-florbetapir SUVR study using cerebellar gray matter, white matter (two different segmentation masks), brainstem, and corpus callosum as reference regions. Methods: We calculated the correlation between 18F-florbetapir PET and concurrent cerebrospinal fluid (CSF) Aβ1–42 levels in a late mild cognitive impairment cohort with longitudinal PET and CSF data over the course of 2 years. In addition to conventional SUVR analysis using mean and median values of normalized brain radiotracer activity, we investigated a new image analysis technique—the weighted two-point correlation function (wS2)—to capture potentially more subtle changes in Aβ-PET data. Results: Compared with the SUVRs normalized to cerebellar gray matter, all cerebral-to-white matter normalization schemes resulted in a higher inverse correlation between PET and CSF Aβ1–42, while the brainstem normalization gave the best results (high and most stable correlation). Compared with the SUVR mean and median values, the wS2 values were associated with the lowest coefficient of variation and highest inverse correlation to CSF Aβ1–42 levels across all time points and reference regions, including the cerebellar gray matter. Conclusions: The selection of reference tissue for normalization and the choice of image analysis method can affect changes in cortical 18F-florbetapir uptake in longitudinal studies.
The Q1 Message Passing Interface (MPI) 3.0 standard includes a significant revision to MPI’s remote memory access (RMA) interface, which provides support for one-sided communication. MPI-3 RMA is expected to greatly enhance the usability and performance ofMPI RMA.We present the first complete implementation of MPI-3 RMA and document implementation techniques and performance optimization opportunities enabled by the new interface. Our implementation targets messaging-based networks and is publicly available in the latest release of the MPICH MPI implementation. Here using this implementation, we explore the performance impact of new MPI-3 functionality and semantics. Results indicate that the MPI-3 RMA interface provides significant advantages over the MPI-2 interface by enabling increased communication concurrency through relaxed semantics in the interface and additional routines that provide new window types, synchronization modes, and atomic operations.
Purpose: Detectors with hexagonal pixels require resampling to square pixels for distortion-free display of acquired images. In this work, the presampling modulation transfer function (MTF) of a hexagonal pixel array photon-counting CdTe detector for region-of-interest fluoroscopy was measured and the optimal square pixel size for resampling was determined. Methods: A 0.65mm thick CdTe Schottky sensor capable of concurrently acquiring up to 3 energy-windowed images was operated in a single energy-window mode to include ≥10 KeV photons. The detector had hexagonal pixels with apothem of 30 microns resulting in pixel spacing of 60 and 51.96 microns along the two orthogonal directions. Images of a tungsten edge test device acquired under IEC RQA5 conditions were double Hough transformed to identify the edge and numerically differentiated. The presampling MTF was determined from the finely sampled line spread function that accounted for the hexagonal sampling. The optimal square pixel size was determined in two ways; the square pixel size for which the aperture function evaluated at the Nyquist frequencies along the two orthogonal directions matched that from the hexagonal pixel aperture functions, and the square pixel size for which the mean absolute difference between the square and hexagonal aperture functions was minimized over all frequencies up to the Nyquist limit. Results: Evaluation of the aperture functions over the entire frequency range resulted in square pixel size of 53 microns with less than 2% difference from the hexagonal pixel. Evaluation of the aperture functions at Nyquist frequencies alone resulted in 54 microns square pixels. For the photon-counting CdTe detector and after resampling to 53 microns square pixels using quadratic interpolation, the presampling MTF at Nyquist frequency of 9.434 cycles/mm along the two directions were 0.501 and 0.507. Conclusion: Hexagonal pixel array photon-counting CdTe detector after resampling to square pixels provides high-resolution imaging suitable for fluoroscopy.
Techniques and mechanisms to detect and compensate for drift by a physically uncloneable function (PUF) circuit. In an embodiment, first state information is registered as reference information to be made available for subsequent evaluation of whether drift by PUF circuitry has occurred. The first state information is associated with a first error correction strength. The first state information is generated based on a first PUF value output by the PUF circuitry. In another embodiment, second state information is determined based on a second PUF value that is output by the PUF circuitry. An evaluation of whether drift has occurred is performed based on the first state information and the second state information, the evaluation including determining whether a threshold error correction strength is exceeded concurrent with a magnitude of error being less than the first error correction strength.
Purpose: Poor pulmonary function (PF) is often considered a contraindication to definitive radiation therapy for lung cancer. This study investigated whether baseline PF was associated with radiation-induced lung toxicity (RILT) in patients with non-small cell lung cancer (NSCLC) receiving conformal radiation therapy (CRT). Methods and Materials: NSCLC patients treated with CRT and tested for PF at baseline were eligible. Baseline predicted values of forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), and diffusion capacity of lung for carbon monoxide (DLCO) were analyzed. Additional factors included age, gender, smoking status, Karnofsky performance status, coexisting chronic obstructive pulmonary disease (COPD), tumor location, histology, concurrent chemotherapy, radiation dose, and mean lung dose (MLD) were evaluated for RILT. The primary endpoint was symptomatic RILT (SRILT), including grade ≥2 radiation pneumonitis and fibrosis. Results: There was a total of 260 patients, and SRILT occurred in 58 (22.3%) of them. Mean FEV1 values for SRILT and non-SRILT patients were 71.7% and 65.9% (P=.077). Under univariate analysis, risk of SRILT increased with MLD (P=.008), the absence of COPD (P=.047), and FEV1 (P=.077). Age (65 split) and MLD were significantly associated with SRILT in multivariate analysis. The addition of FEV1 and age with the MLD-based model slightly improved the predictability of SRILT (area under curve from 0.63-0.70, P=.088). Conclusions: Poor baseline PF does not increase the risk of SRILT, and combining FEV1, age, and MLD may improve the predictive ability.
Immersed finite element methods provide a convenient analysis framework for problems involving geometrically complex domains, such as those found in topology optimization and microstructures for engineered materials. However, their implementation remains a major challenge due to, among other things, the need to apply nontrivial stabilization schemes and generate custom quadrature rules. This article introduces the robust and computationally efficient algorithms and data structures comprising an immersed finite element preprocessing framework. The input to the preprocessor consists of a background mesh and one or more geometries defined on its domain. The output is structured into groups of elements with custom quadrature rules formatted such that common finite element assembly routines may be used without or with only minimal modifications. The key to the preprocessing framework is the construction of material topology information, concurrently with the generation of a quadrature rule, which is then used to perform enrichment and generate stabilization rules. While the algorithmic framework applies to a wide range of immersed finite element methods using different types of meshes, integration, and stabilization schemes, the preprocessor is presented within the context of the extended isogeometric analysis. This method utilizes a structured B-spline mesh, a generalized Heaviside enrichment strategy considering the material layout within individual basis functions’ supports, and face-oriented ghost stabilization. Using a set of examples, the effectiveness of the enrichment and stabilization strategies is demonstrated alongside the preprocessor’s robustness in geometric edge cases. Additionally, the performance and parallel scalability of the implementation are evaluated.
Savannah River National Laboratory (SRNL) has completed a work scope in support of the Savannah River Remediation (SRR) Nitric-Glycolic flowsheet. Glycolic acid will replace formic acid as a reducing agent in the pre-processing of High-Level Waste sludge performed at the Defense Waste Processing Facility (DWPF). Glycolic acid will perform the same function as formic acid, namely reduction of mercury and adjustment of feed rheology and melter oxidation/reduction potential, while significantly reducing the potential for hydrogen generation in DWPF processing. Development testing has demonstrated glycolic acid virtually eliminates hydrogen production in the pre-processing steps. The Nitric-Glycolic flowsheet significantly improves DWPF’s ability to address Savannah River Site’s key challenge - the incorporation of effluent received from the Salt Waste Processing Facility (SWPF). SWPF will deliver significant effluent volume to DWPF, resulting in a concurrent increase in DWPF effluent returned to the Concentration, Storage and Transfer Facilities (CSTF). This work scope demonstrates that glycolate can be destroyed under the Nitric-Glycolic flowsheet prior to returning the DWPF recycle stream to CSTF. To avoid potential flammability issues due to thermolysis of glycolate in CSTF, SRR tasked SRNL to quantify and mitigate glycolate returns via DWPF recycle stream. The development of a strategy for glycolic mitigation initiated with a system’s engineering workshop. Various chemical and/or physical solutions for how to and where to destroy glycolate were considered – consistent with DWPF operational capabilities and process requirements. The workshop identified chemical oxidation of glycolate within the DWPF Recycle Collection Tank (RCT)a as the most promising option with sodium permanganate and Fenton’s reagent (metallic ion catalyzed hydrogen peroxide) as the two most promising oxidants.