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At least 235 records · Page 13

EPR Investigation of Temporal and Thermal Stability of Irradiated Sweeteners

Abstract Electron paramagnetic resonance was used to study the dosimetric properties of commercial sweeteners (sucrose, saccharin, and stevia). The results concluded that sugar has dosimetric properties of interest, which makes it suitable for dose reconstruction, emergency response, and nuclear forensics applications. The radiation dose response was investigated by irradiating samples up to 10 Gy and found to be linear. The post-irradiation stability of samples was observed to be useful for the intended applications. The results showed that the post-irradiation intensities vary from one sample to another, with the general trend demonstrating a small increase in intensities shortly after irradiation followed by an approximately constant leveling out. Finally, the effect of isochronal annealing was studied by heating samples to various temperatures. The results showed an overall stable behavior of the signal below melting temperature.

Environmental Sciences & Ecology↗

Transfer functions for Q A /Q B international regulatory limits for the safe transport of radioactive materials

This paper presents a proposed revision of the International Atomic Energy Agency transport regulations, related to the A 1 and A 2 limit values used to determine the radioactive transport classification. Based on the 'Q system', a novel methodology was introduced to derive Q A and Q B values related to scenarios involving external exposure from a distant source. These values are key parameters that respectively represent the total effective dose and total equivalent dose to the skin, from all primary and secondary particles contributing to radiation exposure. The International Working Group (WG A 1 /A 2 ) is established and associated with the TRANSSC Technical Expert Group on Radiation Protection. A review of the A 1 and A 2 values is performed in response to identified limitations within the existing Q system. The followed approach is based on Monte Carlo simulations that enabled the development of transfer functions aimed at reducing computational time and increasing the flexibility of dose evaluations for any radionuclide with known particle emission spectra. This method allows updating the Q A and Q B values to account for future data evolutions (decay data, fluence-to-dose conversion coefficients) and standardizing the calculation of regulation limits across all referenced radionuclides and scenarios related to external exposure. The transfer functions are established using three Monte Carlo simulation codes—FLUKA, Geant4, and MCNP—and address the previous limitations of the 'Q system', reflecting the latest International Commission for Radiation Protection recommendations and improvements in calculation techniques. The results of the WG show consistent agreement across the codes, with minor discrepancies observed at low primary energies due to statistical uncertainties and different handling of stopping power for electrons/positrons in the codes. This revised approach aligns with current standards and recommendations, ensuring that the radiological consequences of transport accidents are acceptable for the new A 1 and A 2 limits from a radiological protection perspective.

61 RADIATION PROTECTION AND DOSIMETRY↗

Preclinical Risk Evaluation of Normal Tissue Injury With Novel Radiosensitizers

Genotoxic damage induced by radiation triggers a highly coordinated DNA damage response, and molecular inhibitors of key nodes within this complex response network can profoundly enhance the antitumor efficacy of radiation. This is especially true for drugs targeting the catalytic subunit of DNA-dependent protein kinase, which is a core component of the nonhomologous end-joining DNA repair pathway, and ataxia telangiectasia mutated, which coordinates cell cycle arrest, apoptosis, and DNA repair functionalities after radiation exposure. Unlike the more modest in vitro radiosensitizing effects seen with classic sensitizing agents such as cisplatin, 5-fluorouracil, or taxanes, DNA-dependent protein kinase or ataxia telangiectasia mutated inhibitors provide much more robust sensitizing effects in vitro, as might be anticipated from targeting these key DNA repair modulators. However, patients with homozygous inactivating mutations of ataxia telangiectasia mutated or mice with homozygous defects in DNA-dependent protein kinase (severe combined immunodeficiency) have profoundly enhanced acute normal tissue radiation reactions. Therefore, there is significant potential that the combination of small molecule inhibitors of these kinases with radiation could cause similar dose-limiting acute normal tissue toxicities. Similarly, although less understood, inhibition of these DNA repair response pathways could markedly increase the risk of late radiation toxicities. Because these potent radiosensitizers could be highly useful to improve local control of otherwise radiation-resistant tumors, understanding the potential for elevated risks of radiation injury is essential for optimizing therapeutic ratio and developing safe and informative clinical trials. In this review, we will discuss 2 straightforward models to assess the potential for enhanced mucosal toxicity in the oral cavity and small intestine established in our laboratories. We also will discuss similar strategies for evaluating potential drug–radiation interactions with regard to increased risks of debilitating late effects.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

3D Printable Polymers for Radiological Applications

Additive manufacturing of polymers is a widely used and growing technology throughout the DOE complex. Composite filaments for Fused Deposition Modeling (FDM) printers are commonly used to enhance material properties such as mechanical strength, operating temperature and chemical resistance. Radio luminescent properties were added to 3D filaments by impregnating clear poly(ethylene terephthalate)-glycol (PETG) with X-ray scintillator powder. X-ray scintillators have unique, narrow emission spectra which can be imaged with low light DSLR cameras, photomultiplier tubes, or spectrometers. Filament Production: 1. Pellets are loaded into the hopper. 2. Temperature and extrusion speed are set on extruder. 3. Extruder turned on and filament is pulled from nozzle along air path to cool. 4. Spooler drive speeds set. 5. Filament is inserted through Filameasure then guided along drive wheels and into traverse. 6. Parameters adjusted to obtain 1.75 mm diameter 7. Filament is inserted into spooler wheel. Traverse speed set and slip nut adjusted to make tight and even roll. From Raw Materials to Printed Part: Clear PETG pellets were dipped in ZnS:Cu scintillator powder to coat pellets. Coated and uncoated pellets were mixed together before inserting into hopper. Filament showed trace amounts of powder and luminesced under UV light. Powder distribution is random and not reproducible thus providing a unique identification marker potentially useful for national security applications. Multiple X-ray scintillators can be arranged in a panel to discriminate incident X-ray photon energies. Variable panel arrangement: pixelated, layered, solid from homogenous filament. Ratio of emission intensities. Response varies with incident photon energy. Spectrally separate scintillators. Scintillators: Yttrium Oxide Europium Doped - Red, Gadolinium Oxysulfide Terbium Doped - Green, Barium Magnesium Aluminate Europium Doped - Blue, Zinc Sulfide Copper Doped - Green. Powder concentrations will need to be increased in the filament for use in the energy discriminating panel. Homogeneity in the filament will be a challenge that can be solved by turning the pellets into a powder and mixing it with scintillator powder prior to extrusion. The panels will be tested using x-ray booths and button sources such as Am-241, Cs-137, and Co-60.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Field deployable trace radioisotope analysis through combined electrochemical and alpha spectroscopy methods

A method for depositing actinides directly onto a 4H-SiC Schottky barrier diode (SBD) detector as a field deployable actinides sensor was developed to enable off-site analysis, shortening the time to obtain critical information such as elements, concentration, and/or isotopic ratio related to the radiological situation. A thin film of Hg was first electrodeposited onto the Pt contact of the SiC diode, followed by chronoamperometric deposition of microgram levels of actinides under conventional control conditions. The 4H-SiC diode maintained consistent functionality through the electrodeposition process and showed resolved alpha-energy spectra that contained accurate isotopic information demonstrating the feasibility of a combined chemical and radiological sensor for field actinide detection and quantification.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗

Phase I Final Technical Report _ RDUSA

During Phase I of this proposal our team focused on meeting the goals proposed in the Phase I project which included identifying the integration approaches and fundamental materials properties (composition, bonding, defects, structure, doping, etc.) defining response to X-ray energies between 10-100KeV and sensitivity >100 μC Gyair-1 cm-2 in perovskite systems with formula CsPbX3 and CsPb2X5 [where X = chlorine (Cl), bromine (Br), iodine (I), or a combination of any of these elements] to enable high-efficiency, low-cost, X-ray detection systems. In the sections below, we summarize the research results that confirm the feasibility of our technical approach. In summary, we have demonstrated X-ray sensitivity >500 μC Gyair-1 cm-2 in the energy range of 10-100 keV using CsPbBr3 films of thicknesses ranging from 8 μm to 500 μm, which is above the technical requirements outlined in the call for proposal.

36 MATERIALS SCIENCE↗

A Preliminary Radiological Risk Assessment Model for Disposition of Remote-Handled Transuranic Wastes at Los Alamos National Laboratory Area G - 20116

The U.S. Department of Energy (DOE) operates a low-level radioactive waste (LLW) disposal site at Material Disposal Area G, in Los Alamos, New Mexico, USA. Area G has been the primary LLW disposal site for Los Alamos National Laboratory (LANL) since the 1960's. In addition to LLW, Area G is host to a variety of other wastes, the disposition of which must be determined before closure of the site. A probabilistic Radiological Risk Assessment (RRA) for Area G is used in order to support decision making regarding some wastes that are not addressed in the extant Area G Performance Assessment (PA) and Composite Analysis (CA). Between 1979 and 1987, 33 special shafts were augered into the Bandelier Tuff at Area G. This volcanic tuff is present across Pajarito Plateau on the eastern slopes of the Jemez Mountains, and varies widely in its consistency, from weakly indurated non-welded layers to welded layers that uphold the mesa cliffs of the Plateau. These mesas are home to LANL, Area G, and the townsites of Los Alamos and White Rock, with residences about 1400 m from Area G. The 33 Shafts were lined with steel casing, and contain remote-handled (RH) transuranic wastes (TRU) resulting from experiments and analysis performed in special glove boxes at the Chemistry and Metallurgy Research (CMR) facility at LANL. Some of these wastes originated as used nuclear fuel. The purpose of the Area G RRA is to evaluate the potential future risk to humans and the environment from the RH TRU in the 33 Shafts in the context of the risk associated with the surrounding wastes at Area G. The analysis is responsive to expectations outlined in DOE Order 458.1, Radiation Protection of the Public and the Environment, and is informed by the Manual and Guidance accompanying DOE O 435.1, Radioactive Waste Management. Because the waste meets the definition of TRU, the regulatory context necessarily takes into consideration the regulation governing the disposal of TRU from the U.S. Environmental Protection Agency (EPA): 40 CFR 191, Environmental Radiation Protection Standards for Management and Disposal of Spent Nuclear Fuel, High-Level and Transuranic Radioactive Wastes. Given the broader regulatory context for the RRA, the analysis is subject to different assumptions from those made in the existing DOE O 435.1 PA and CA, such as allowing for future occupation of the site. The analysis begins with a comprehensive evaluation of features, events, processes, and exposure scenarios (FEPS) for Area G and the wastes it contains. These FEPSs are screened to eliminate from further consideration those of extremely low probability and/or consequence, and a conceptual site model (CSM) is subsequently developed. The scope and structure of the Area G RRA Model is informed by this CSM, and the Area G RRA Model is developed using the GoldSim systems analysis modeling platform. This paper presents the initial version of a defensible, transparent, and reasonably realistic model, which is based on the state of knowledge of the wastes, the site, and the FEPSs that govern contaminant transport from wastes into the environment and subsequent exposures to humans and other biota. Probabilistic model input distributions represent uncertainties inherent in the real and modeled systems. The results of the Area G RRA Model inform decisions regarding the disposition of the RH TRU in the 33 Shafts. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Large Eddy Simulations of Turbulent and Buoyant Flows in Urban and Complex Terrain Areas Using the Aeolus Model

Fast and accurate predictions of the flow and transport of materials in urban and complex terrain areas are challenging because of the heterogeneity of buildings and land features of different shapes and sizes connected by canyons and channels, which results in complex patterns of turbulence that can enhance material concentrations in certain regions. To address this challenge, we have developed an efficient three-dimensional computational fluid dynamics (CFD) code called Aeolus that is based on first principles for predicting transport and dispersion of materials in complex terrain and urban areas. The model can be run in a very efficient Reynolds average Navier–Stokes (RANS) mode or a detailed large eddy simulation (LES) mode. The RANS version of Aeolus was previously validated against field data for tracer gas and radiological dispersal releases. As a part of this work, we have validated the Aeolus model in LES mode against two different sets of data: (1) turbulence quantities measured in complex terrain at Askervein Hill; and (2) wind and tracer data from the Joint Urban 2003 field campaign for urban topography. As a third set-up, we have applied Aeolus to simulate cloud rise dynamics for buoyant plumes from high-temperature explosions. For all three cases, Aeolus LES predictions compare well to observations and other models. These results indicate that Aeolus LES can be used to accurately simulate turbulent flow and transport for a wide range of applications and scales.

42 ENGINEERING↗

Current Status of Clinical Trials for Cervical and Uterine Cancer Using Immunotherapy Combined With Radiation

Novel therapies combined with radiation continue to be of significant interest in the developmental treatment paradigm of gynecologic cancers. Clinical implementation of immunotherapy in oncology has rapidly changed the treatment landscape, options, paradigm, and outcomes through clinical trials. Immunotherapy has emerged as a therapeutic pillar in the treatment of solid tumors with demonstrable synergistic activity when combined with radiation therapy and chemoradiotherapy by an alteration or enhancement of the immune system. In solid tumors, radiation therapy induces migration of dendritic cells, T cell activation, and proliferation, and increases in tumor-infiltrating lymphocytes. These immunomodulatory effects in conjunction with immune checkpoint blockade are currently under active investigation in the adjuvant, definitive, and metastatic settings. Results from early phase trials demonstrate promising efficacy and overall tolerable toxicity profiles of combined modality treatment. There is significant interest in optimizing the treatment for patients with locally advanced cervical cancer beyond the standard of care—chemoradiation—which has been in place for the last 30 years. The majority of cervical cancer emerges after persistent infection with a high-risk subtype of the human papillomavirus, where viral oncoproteins lead to cellular changes and immortalization. As a result, immune tolerance can develop, resulting in cancer. Knowledge of the mechanism of human papillomavirus–related oncogenesis suggests that immune therapy or checkpoint blockade can reinvigorate an antitumor immune response. Current clinical trials are exploring the therapeutic potential of these approaches. Uterine cancers have been grouped into 4 molecular subclasses by their driver mutations, mutational burden, and copy-number alterations. Of these subgroups, the polymerase epsilon–mutated and microsatellite-unstable may represent up to 40% of endometrial cancers, and they have been shown to be immunogenic. Because of the inherent immunogenicity of these MSI-high tumors, combined immune modulation strategies, including chemotherapy, radiation, and immunotherapy and immune checkpoint inhibitor therapy, are being explored to improve treatment outcomes. In this review, we explore current immunomodulatory and multimodality therapeutic approaches in the treatment of cervical and uterine cancer through ongoing clinical trials investigating the combination of immunotherapy and radiation therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Is Mini Beam Ready for Human Trials? Results of Randomized Study of Treating De-Novo Brain Tumors in Canines Using Linear Accelerator Generated Mini Beams

The main challenge in treating malignant brain neoplasms lies in eradicating the tumor while minimizing treatmentrelated damage. Conventional radiation treatments are associated with considerable side effects. Synchrotron generated micro-beam radiation (SMBRT) has shown to preserve brain architecture while killing tumor cells, however physical characteristics and limited facility access restrict its use. We have created a new clinical device which produces mini beams on a linear accelerator, to provide a new type of treatment called mini-beam radiation therapy (MBRT). The objective of this study is to compare the treatment outcomes of linear accelerator based MBRT versus standard radiation treatment (SRT), to evaluate the tumor response and the treatment-related changes in the normal brain with respect to each treatment type. Pet dogs with de-novo brain tumors were accrued for treatment. Dogs were randomized between standard fractionated stereotactic (9 Gy in 3 fractions) radiation treatment vs. a single fraction of MBRT (26 Gy mean dose). Dogs were monitored after treatment for clinical assessment and imaging. When the dogs were euthanized, a veterinary pathologist assessed the radiation changes and tumor response. We accrued 16 dogs, 8 dogs in each treatment arm. In the MBRT arm, 71% dogs achieved complete pathological remission. The radiation-related changes were all confined to the target region. Structural damage was not observed in the beam path outside of the target region. In contrast, none of the dogs in control group achieved remission and the treatment related damage was more extensive. Therapeutic superiority was observed with MBRT, including both tumor control and the normal structural preservation. The MBRT findings are suggestive of an immune related mechanism which is absent in standard treatment. These findings together with the widespread availability of clinical linear accelerators make MBRT a promising research topic to explore further treatment and clinical trial opportunities.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

An Overview of the State-of-the-Art Reactor Consequence Uncertainty Assessment Accident Progression Insights

The U.S. Nuclear Regulatory Commission (NRC) with Sandia National Laboratories (Sandia) have completed three uncertainty analyses (UAs) as part of the State-of-the-Art Reactor Consequence Analyses (SOARCA) program. The SOARCA UAs included an integrated evaluation of uncertainty in accident progression, radiological release, and offsite health consequence projections. The UA for Peach Bottom, a boiling-water reactor (BWR) with a Mark I containment located in the State of Pennsylvania, analyzed the unmitigated long-term station blackout SOARCA scenario. The UA for Sequoyah, a 4-loop Westinghouse pressurized-water reactor (PWR) located in the State of Tennessee, analyzed the unmitigated short-term station blackout SOARCA scenario, with a focus on issues unique to the ice condenser containment and the potential for early containment failure due to hydrogen deflagration. The UA for Surry, a 3-loop Westinghouse PWR with a sub-atmospheric large dry containment located in the State of Virginia, analyzed the unmitigated short-term station blackout SOARCA scenario including the potential for thermally-induced steam-generator tube rupture. These three UAs are currently documented in three NUREG/CR reports. This report provides input to planned NRC documentation on the insights and findings from the SOARCA UA program. The purpose of the summary report is to provide a useful reference for regulatory applications that require the evaluation of offsite consequence risk from beyond design basis event severe accidents. This report focuses on the accident progression and source term insights developed from the MELCOR analyses. MELCOR is the NRC's best-estimate, severe accident computer code used in the SOARCA UAs. In anticipation of the SOARCA UA insights work, NRC and Sandia benchmarked the response of the Peach Bottom model to selected reference calculations from the Peach Bottom SOARCA UA. Peach Bottom was the first SOARCA UA performed and was completed in 2015 using the MELCOR 1.8.6 code. The PWR SOARCA UAs evolved the original methodology and utilized the updated MELCOR 2.2 computer code. The Peach Bottom model has been systematically updated for other NRC research efforts and has been updated to MELCOR 2.2. computer code. The findings from the new reference calculations using the updated model with the MELCOR 2.2 code are also integrated into the report. A second objective is an assessment of the applicability of the results to the other nuclear reactors in the U.S. As the key findings are reviewed, judgments are presented on the applicability of the results to other U.S. nuclear power plants. An important objective of the SOARCA program relied on high- fidelity plant-specific modeling. However, the nature of the insights and conclusions allowed judgements to be made on the applicability of the various insights to the same general classification of plant (i.e., BWR or PWR) or the entire fleet of plants. Finally, the results from the SOARCA UA accident progression calculations contain a wealth of information not previously documented in the NUREG/CRs. This report includes new but related information that can be used to benchmark past or support future regulatory decisions related to severe accidents. The new work includes a benchmark of the NUREG-1465 licensing source term definitions, the variability of key accident progression events and timing to radionuclide release, and an improved understanding of the timing and source terms from consequential steam generator tube ruptures. iii ACKNOWLEDGEMENTS The Sandia authors gratefully acknowledge the significant technical and programmatic contributions from the NRC SOARCA team which are reflected throughout the report. Dr. Tina Ghosh has been involved throughout the SOARCA UAs, providing the primary managerial and technical oversight. The long lists of NRC and Sandia contributors from the SOARCA UAs are cited in the three NUREG/CRs and are also gratefully acknowledged by the small team of authors compiling the results of their efforts. Significant technical contributions, advice, and reviews were provided by Dr. Hossein Esmaili, Dr. Alfred Hathaway, and Dr. Edward Fuller (retired) of the NRC. Dr. Randal Gauntt (retired), Mr. Patrick Mattie, Mr. Joseph Jones (retired), and Dr. Doug Osborn from Sandia are recognized as the SOARCA UA managers guiding the past efforts. There is a comparable list of project managers at the NRC including Ms. Patricia Santiago, Dr. Salman Haq, and Mr. Jon Barr. Sadly, we have lost Mr. Charlie Tinkler and Mr. Robert Prato, who were important contributors to the original SOARCA project. Finally, Mr. Kyle Ross and Mr. Mark Leonard have also retired but were significant technical contributors. Mr. Kyle Ross was the technical lead on all three SOARCA UAs and the original pressurized water reactor SOARCA study. Mr. Leonard was the technical lead on the original boiling water reactor SOARCA study and a key contributor to the first Peach Bottom SOARCA UA. iv

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

Contentious narratives and disinformation about nuclear weapons in strategic deterrence and competition: A SOCOM perspective. Part of Section: United States Special Operations Command (USSOCOM) in Emerging Strategic & Geopolitical Challenges: Operational Implications for US Combatant Commands

Russia’s “special military operation” in Ukraine demonstrates the challenge for strategic deterrence and competition of countering contentious narratives and disinformation about weapons of mass destruction (WMD) during conventional regional wars against a nucleararmed adversary. Moscow uses both tailored, contentious narratives and targeted disinformation about WMD in Ukraine to influence and disrupt local and global perceptions in support of its deterrence and competition objectives vis-à-vis the United States and NATO. Since December 2021, Moscow has made a focal point of chemical, biological, radiological, and nuclear weapons in its efforts to establish a permissive environment for its military buildup on the border with Ukraine and then its military intervention. These information tactics also demonstrate an opportunity for US Special Operations Forces (SOF). They are a case study for considering how SOF can contribute to strategic deterrence and competition objectives, specifically countering adversary gray-zone information efforts to alter regional security orders.1 Such a role is in line with the 2022 Special Operations Forces Vision and Strategy, which provides a framework for the evolution of SOF into “a force capable of creating strategic, asymmetric advantages for the nation as a key contributor of integrated deterrence” (United States Special Operations Command, 2022). This paper briefly examines this strategic challenge and SOF opportunity, focusing narrowly on the distinction between contentious narratives and disinformation about nuclear weapons and the role of SOF in countering these gray-zone information tactics. The nuclear dimension of Moscow’s contentious narratives and disinformation in the “special military operation” is of particular interest because it demonstrates the distinction between strategic efforts to influence and disrupt local and global perceptions in Moscow’s favor. This distinction between influence and disruption is less clear with Russia’s contentious narratives and disinformation about chemical and biological weapons in Ukraine, as disinformation about these two types of WMD appears to overwhelm contentious narratives. We believe this distinction is useful for policymakers and warfighters responsible for countering gray-zone information tactics because it provides a framework for crafting tailored responses to contentious narratives and disinformation about nuclear weapons and other WMD. The chapter concludes with a discussion of efforts that could be undertaken by SOF in cooperation with other relevant stakeholders to address this aspect of adversary gray-zone information tactics.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗

DUAL-PARTICLE DOSEMETER BASED ON ORGANIC SCINTILLATOR

Abstract Traditionally available handheld dosemeters are generally sensitive to only one type of radiation: neutrons or photons. Some dosemeters also rely on very specific attenuation correlations between response and dose, are not scalable in size and multiple dosemeters are required to characterise mixed-particle fields. The research presented here serves as a proof-of-concept for a method to simultaneously measure dose rates from neutrons and photons using a particle discriminating organic scintillation detector without the need for spectral deconvolution. The method was compared with traditional instruments and to simulation. Isotopic photon dose rates measured with this method were within 4% of simulated truth, whereas fission spectrum neutron dose rates were measured within 21%. Measurements of dose rates from both particles agree with simulated truth better than traditional instruments. This new method allows for measurement of dose equivalent from both neutrons and photons with a single instrument and no reliance on spectral deconvolution.

Miller, C. A.↗

Expedited Walkdowns and Preparation of Cost Estimates for Decontamination and Demolition of Excess Facilities - 20335

Lawrence Livermore National Security, LLC (LLNS) is the prime contractor responsible for managing and operating Lawrence Livermore National Laboratory (LLNL). The mission of the LLNL is to strengthen security of the United States through development and application of world-class science and technology to enhance the nation's defense, reduce the global threat from terrorism and weapons of mass destruction, and respond with vision, quality, integrity, and technical excellence to scientific issues of national importance. To accomplish its mission, LLNL must plan and manage its campus space and facilities to optimize use of its relatively small one-square-mile footprint. LLNL currently has numerous excess facilities that require decontamination and demolition (D and D). The LLNL Legacy Facility Program is responsible for stewardship and risk reduction programs to effectively manage these excess assets at LLNL. The Legacy Facility Program identified 10 excess facilities at LLNL that were candidates for demolition based on risks from further degradation of the facilities, potential exposure to hazardous materials, or need for removal to make way for new program facilities. The buildings range from a structure built in 1943 to serve as a US Navy drill hall during World War II, to a facility that provided neutrons to study material properties for the fusion energy program. The National Nuclear Security Administration (NNSA) appropriated FY19 funding for the development of Class 3 estimates for these 10 excess facilities that would be used to develop a Program Management Plan for funding consideration. Class 3 estimates are not conceptual, nor overly detailed, but adequate to be used for budget and appropriation purposes. Using existing strategic sourcing agreements, LLNL was able to organize a team of senior subject matter experts (SMEs) with diverse technical backgrounds across the Department of Energy (DOE) Complex to complete extensive process knowledge (PK) reviews and walk-downs of each excess facility and to deliver accurate and complete estimates under an expedited schedule (i.e., within eight weeks). To facilitate the expedited schedule, LLNL was fully prepared for the arrival of the JGMS team, which consisted of the following companies: J.G. Management Systems, Inc. (JGMS); Strata-G, LLC; and Michael Baker International. LLNL provided background and PK information on the excess facilities, pictures, supporting historical documentation, and radiological survey history as well as escorted access to the facilities. The JGMS team has previous experience supporting Program Management Plans for excess facilities at the Y-12 National Security Complex. The team mobilized to LLNL and performed the facility walk-downs from January 22-25, 2019. Using a methodical evaluation process, expertise, and experience, the team was able to deliver walk-down draft reports and estimates to LLNL before their February 8, 2019 deadline. LLNL then in turn reviewed, completed the estimates by adding waste management costs and other LLNL costs, and delivered the estimates to NNSA by February 15, 2019. The completed final reports, including draft D and D estimates, were delivered to LLNL before their March 6, 2019 deadline. The work was successfully completed ahead of the expedited schedule required by LLNL, resulting in a commendation from the client. This paper describes how the partnership and collaboration as a fully integrated team comprised of the prime contractor, LLNS, and the JGMS team successfully met the needs of the US government, resulting in the performance of expedited site walk-downs, the development of summary evaluation reports, and the preparation of draft Class 3 estimates and preliminary schedules for the D and D of 10 excess facilities at LLNL. The efforts of the team will enable the D and D of the first excess facility in the 2020-2021 time frame. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Targeting the Y-box Binding Protein-1 Axis to Overcome Radiochemotherapy Resistance in Solid Tumors

Multifunctional Y-box binding protein-1 (YB-1) is highly expressed in different human solid tumors and is involved in various cellular processes. DNA damage is the major mechanism by which radiochemotherapy (RCT) induces cell death. On induction of DNA damage, a multicomponent signal transduction network, known as the DNA damage response, is activated to induce cell cycle arrest and initiate DNA repair, which protects cells against damage. YB-1 regulates nearly all cancer hallmarks described to date by participating in DNA damage response, gene transcription, mRNA splicing, translation, and tumor stemness. YB-1 lacks kinase activity, and p90 ribosomal S6 kinase and AKT are the key kinases within the RAS/mitogen-activated protein kinase and phosphoinositide 3-kinase pathways that directly activate YB-1. Thus, the molecular targeting of ribosomal S6 kinase and AKT is thought to be the most effective strategy for blocking the cellular function of YB-1 in human solid tumors. In this review, after describing the prosurvival effect of YB-1 with a focus on DNA damage repair and cancer cell stemness, clinical evidence will be provided indicating an inverse correlation between YB-1 expression and the treatment outcome of solid tumors after RCT. In the interest of being concise, YB-1 signaling cascades will be briefly discussed and the current literature on YB-1 posttranslational modifications will be summarized. Finally, the current status of targeting the YB-1 axis, especially in combination with RCT, will be highlighted.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Modeling inter‐reader variability in clinical target volume delineation for soft tissue sarcomas using diffusion model

Abstract Background Accurate delineation of the clinical target volume (CTV) is essential in the radiotherapy treatment of soft tissue sarcomas. However, this process is subject to inter‐reader variability due to the need for clinical assessment of risk and extent of potential microscopic spread. This can lead to inconsistencies in treatment planning, potentially impacting treatment outcomes. Most existing automatic CTV delineation methods do not account for this variability and can only generate a single CTV for each case. Purpose This study aims to develop a deep learning‐based technique to generate multiple CTV contours for each case, simulating the inter‐reader variability in the clinical practice. Methods We employed a publicly available dataset consisting of fluorodeoxyglucose positron emission tomography (FDG‐PET), x‐ray computed tomography (CT), and pre‐contrast T1‐weighted magnetic resonance imaging (MRI) scans from 51 patients with soft tissue sarcoma, along with an independent validation set containing five additional patients. An experienced reader drew a contour of the gross tumor volume (GTV) for each patient based on multi‐modality images. Subsequently, two additional readers, together with the first one, were responsible for contouring three CTVs in total based on the GTV. We developed a diffusion model‐based deep learning method that is capable of generating arbitrary number of different and plausible CTVs to mimic the inter‐reader variability in CTV delineation. The proposed model incorporates a separate encoder to extract features from the GTV masks, leveraging the critical role of GTV information in accurate CTV delineation. Results The proposed diffusion model demonstrated superior performance with the highest Dice Index (0.902 compared to values below 0.881 for state‐of‐the‐art models) and the best generalized energy distance (GED) (0.209 compared to values exceeding 0.221 for state‐of‐the‐art models). It also achieved the second‐highest recall and precision metrics among the compared ambiguous image segmentation models. Results from both datasets exhibited consistent trends, reinforcing the reliability of our findings. Additionally, ablation studies exploring different model structures and input configurations highlighted the significance of incorporating prior GTV information for accurate CTV delineation. Conclusions The proposed diffusion model successfully generates multiple plausible CTV contours for soft tissue sarcomas, effectively capturing inter‐reader variability in CTV delineation.

Dong, Yafei [Yale Biomedical Imaging Institute Yal↗

A Framework for Patient-Centered Pathways of Care for Radiopharmaceutical Therapy: An ASTRO Consensus Document

Radiopharmaceutical therapy (RPT) is an area of projected growth and importance with several agents in clinical use, new agents in late-phase clinical trials, and many others under testing and development. This article proposes a framework for developing pathways of care that can be broadly applied to all RPTs, representing the current status of RPT. It suggests foundational elements for many pathways of care for patients with cancer and concludes with areas in active development and the future horizon for RPT treatment centers. Developing a framework for patient-centered pathways of care is a critical step in establishing RPT as standard therapy for patients with a diverse spectrum of cancers. This expected increase in RPT treatment options will affect a much larger population of patients with complex cancer. It will also require enhanced coordination and collaboration among appropriately qualified personnel with diverse expertise in image acquisition, image interpretation, quantitative imaging, dosimetry calculation, radiation quality assurance and safety as well as oncology care and RPT-induced sequelae and response assessment. The essential role of this evolving RPT care team within multidisciplinary oncology care is a cornerstone of this framework for a patient-centered pathway of care for RPT. Given the status of current RPT practice and the horizon for future applications, this patient-centered pathway of care guidance is timely and should help inform future clinical RPT practice paradigms. A task force was recruited from the Theranostic Working Group of the American Society for Radiation Oncology (ASTRO) in May 2019 with equal representation from the nuclear medicine community. The task force expanded on a framework that was originally conceived by the Working Group for patient-centered care. This framework was developed to incorporate the strengths of both radiation oncologists and nuclear medicine physicians. The manuscript was then developed by the task force and posted on the ASTRO website for a 6-week public comment period ending in July 2020. Comments were adjudicated, and the draft was sent to external organizations for potential endorsement. This document was sent to the ASTRO Board of Directors in October 2020 for approval.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Continuum radiated power density $(P^{\textrm{C}}_{\textrm{rad}})$ and effective charge $(Z_{\textrm{eff}})$ estimates from multi-energy photon-counting measurements

Multi-energy soft x-ray pinhole cameras have been designed, built, calibrated, and operated at Madison symmetric Torus, Alcator C-Mod, and more recently at Tokamak a configuration variable and Tungsten Environment in Steady-State Tokamak (WEST), to measure plasma emission across multiple energy ranges. Here we describe a new methodology to estimate the local continuum radiated power density and the plasma effective charge (Z eff ) directly from photon-counting measurements of the line-free continuum emission (Bremsstrahlung and Radiative Recombination) in several energy bands between 11 and 18 keV. This capability is particularly valuable for confinement systems using metal plasma-facing components, where x-ray losses from interactions with the sputtered wall can represent a significant fraction of the total radiated power (P rad ). The approach leverages a well-characterized detector responsivity, modeled by a complementary error function, and interprets the differential multi-energy measurements between adjacent energy levels through the probability density function of a Gaussian distribution. The implementation of this diagnostic technique is currently under development on the WEST tokamak, aiming at the goal of providing real-time P rad and Z eff measurements during long-pulse operation (up to 1000 s) in the 2026 campaign.

WEST↗