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Development of Training Materials for Pathologists to Provide Machine Learning Validation Data of Tumor-Infiltrating Lymphocytes in Breast Cancer

The High Throughput Truthing project aims to develop a dataset for validating artificial intelligence and machine learning models (AI/ML) fit for regulatory purposes. The context of this AI/ML validation dataset is the reporting of stromal tumor-infiltrating lymphocytes (sTILs) density evaluations in hematoxylin and eosin-stained invasive breast cancer biopsy specimens. After completing the pilot study, we found notable variability in the sTILs estimates as well as inconsistencies and gaps in the provided training to pathologists. Using the pilot study data and an expert panel, we created custom training materials to improve pathologist annotation quality for the pivotal study. We categorized regions of interest (ROIs) based on their mean sTILs density and selected ROIs with the highest and lowest sTILs variability. In a series of eight one-hour sessions, the expert panel reviewed each ROI and provided verbal density estimates and comments on features that confounded the sTILs evaluation. We aggregated and shaped the comments to identify pitfalls and instructions to improve our training materials. From these selected ROIs, we created a training set and proficiency test set to improve pathologist training with the goal to improve data collection for the pivotal study. We are not exploring AI/ML performance in this paper. Instead, we are creating materials that will train crowd-sourced pathologists to be the reference standard in a pivotal study to create an AI/ML model validation dataset. The issues discussed here are also important for clinicians to understand about the evaluation of sTILs in clinical practice and can provide insight to developers of AI/ML models.

60 APPLIED LIFE SCIENCES↗

The three R's of training: Recording, Retaining, and Reporting - The training management system that synergizes

NASA's Kennedy Space Center employs a Training and Certification Record System (TCRS) which tracks and maintains records for each of its employees, encompassing all aspects of training history: training courses, physical examinations, proficiency tests, on-the-job training, standboards, and certifications with completions and expiration dates. TCRS, which is fully automated, includes an expiration-alert notification capability to project recurring expirations, thereby functioning as a forecasting tool for training budgets.

Ingram, Dick D.↗

Why accredit ISO/CEI 17025 a nuclear waste management laboratory? - 15112

When there is no storage, nor repository, available on a site, the entity in charge of nuclear waste management should find outlets in order to evacuate outside the site. Each outlet has his rules and waste acceptance criteria (packaging rules, physical/chemical/radiological criteria for example). Before you are able to evacuate your waste, an acceptance's process (or contract review) takes place. This process scans the entire measures implemented by the site in order to satisfy outlet's criteria. When the acceptance is obtained, shipments could be organized, and the process gets into an observation's phase. During this phase, the outlet could choose to inspect a finished nuclear waste package or to audit regularly the waste management process. In this last case, the outlet re-scans the entire documents and implemented measures. This audit lasts from one to several days. A way to tackle/approach the audit is to acknowledge, by a trusted third party (i.e. independent from the outlet), all or part of waste management system, in order to base one's reputation on this organism and win outlet's trust. For this purpose, the entity could choose certification or accreditation. Certification (ISO 9001 as often as not) aims at evaluating a system for managing the quality of one product or service. Accreditation (ISO 17025, for example) provides formal recognition for technical skills within a quality management system (clauses 5 and 4 of the ISO 17025 standard). In 2006, the LDM laboratory is the first French laboratory accredited, in accordance with ISO 17025 standard, for the characterization by gamma spectrometry on 100 L- and 200 L- radioactive waste drums (accreditation No 1-1712 - scope available on www.cofrac.fr). This accreditation allows the lab: - to update the quality management system, - to compile the entire technical file of the gamma-ray assay (description, evaluation of the uncertainties, calibration, proficiency testing programs, measurement procedures,...), - to pass previous identified constraints on to producers and nuclear waste package production, - to maintain permanent quality improvement loop, - to lighten the programs of outlets audits, through the acknowledgement of the technical competence of the laboratory to evaluate by gamma spectrometry the activity contained in our nuclear waste drums. On the other hand, the lab is re-evaluated periodically to ensure its continued compliance with requirements: within a 12 month's interval for an internal audit, with a 18 month's period for COFRAC (French sole official national accreditation body). Since 2006, the lab is accredited. His accreditation renewed in 2010. A new entire renewal audit is planned in 2015. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Approach to Quality Assurance for Complex Environmental Modeling - 20407

A strong Quality Assurance (QA) program for complex environmental modeling is essential for regulatory and public acceptance and trust, but it does not have to be onerous. Neptune and Company, Inc. (Neptune) has developed a strong QA program that improves transparency, traceability, reproducibility, and therefore, defensibility and trust. Neptune's QA program has evolved over the past 27 years, transitioning from an ad hoc QA program, to a program that is currently Nuclear Quality Assurance-1 (NQA-1) compliant, and will soon be NQA-1/DOE approved for DOE EM modeling work. In addition, Neptune is a qualified laboratory assessor and qualified auditor for reference materials, a proficiency testing provider, and fully complies with the Environmental Protection Agency (EPA) QA program. Neptune's President and CEO, Kelly Black, was recently named the Chairperson of the International Organization for Standardization (ISO) Technical Committee 69, Application of Statistical Methods. A strong QA program has been developed for Neptune's radiological performance assessment (PA) program. Although pieces of their QA program are currently in development, their current program includes document control using Subversion, issue tracking and work flow tracking using JIRA, and transparency and traceability via a system of 'calc sheets' for documentation of all data analysis and modeling combined with 'check print' documentation of QA checking, and rigorous model testing and configuration control. All work is reviewed by an independent subject matter expert who is not associated with the collection and assembly of information, for an internal peer review. The program is enforced with a handful of Standard Operation Procedures (SOPs), Work Instructions, QA Project Plans (QAPPs), and Quality Management Plans (QMPs) that are updated frequently, with required annual training and acknowledgment. In addition, effective communication of modeling approaches and results to clients and stakeholders are integral to their QA program. Many of their models are built using the GoldSim modeling platform, for which their models are well-known for their level of transparency, documentation, and QA traceability. This level of QA is also applied to their process-level models. Neptune has taken some lessons learned from the extremely rigorous QA program required for the Yucca Mountain Project (YMP), and imposed the YMP requirements of complete traceability, transparency, and reproducibility, but avoided the inflexibility of a QA program that likely contributed to the suspect e-mails in 2005 that resulted in loss of trust in the YMP, and in nuclear waste disposal (and nuclear power) in general. There are far too many examples of loss of public trust due to poor QA that could have been easily avoided with a simple and straight-forward QA program combined with stakeholder engagement. The purpose of this paper is to share features of Neptune's Radiological Performance Assessment program QA program, and some of their QA related lessons learned over the past 27 years of QA for complex environmental modeling. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Integrated Data Collection Analysis (IDCA) Program - AN and Bullseye Smokeless Powder

The Integrated Data Collection Analysis (IDCA) program is conducting a proficiency study for Small- Scale Safety and Thermal (SSST) testing of homemade explosives (HMEs). Described here are the results for impact, friction, electrostatic discharge, and differential scanning calorimetry analysis of ammonium nitrate (AN) mixed with Bullseye® smokeless powder (Gunpowder). The participants found the AN/Gunpowder to: 1) have a range of sensitivity to impact, comparable to or less than RDX, 2) be fairly insensitive to friction as measured by BAM and ABL, 3) have a range for ESD, from insensitive to more sensitive than PETN, and 4) have thermal sensitivity about the same as PETN and Gunpowder. This effort, funded by the Department of Homeland Security (DHS), is putting the issues of safe handling of these materials in perspective with standard military explosives. The study is adding SSST testing results for a broad suite of different HMEs to the literature. Ultimately the study has the potential to suggest new guidelines and methods and possibly establish the SSST testing accuracies needed when developing safe handling practices for HMEs. Each participating testing laboratory uses identical test materials and preparation methods. Note, however, the test procedures differ among the laboratories. The testing performers involved are Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory (LANL), Indian Head Division, Naval Surface Warfare Center, (NSWC IHD), Sandia National Laboratories (SNL), and Air Force Research Laboratory (AFRL/RXQL). These tests are conducted as a proficiency study in order to establish some consistency in test protocols, procedures, and experiments and to compare results when these testing variables cannot be made consistent. Keywords: Small-scale safety testing, proficiency test, impact-, friction-, spark discharge-, thermal testing, round-robin test, safety testing protocols, HME, RDX, potassium perchlorate, potassium chlorate, sodium chlorate, sugar, dodecane, PETN, carbon, ammonium nitrate, Gunpowder, Bullseye® smokeless powder.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Integrated Data Collection Analysis (IDCA) Program - SSST Testing Methods

The Integrated Data Collection Analysis (IDCA) program is conducting a proficiency study for Small- Scale Safety and Thermal (SSST) testing of homemade explosives (HMEs). Described here are the methods used for impact, friction, electrostatic discharge, and differential scanning calorimetry analysis during the IDCA program. These methods changed throughout the Proficiency Test and the reasons for these changes are documented in this report. The most significant modifications in standard testing methods are: 1) including one specified sandpaper in impact testing among all the participants, 2) diversifying liquid test methods for selected participants, and 3) including sealed sample holders for thermal testing by at least one participant. This effort, funded by the Department of Homeland Security (DHS), is putting the issues of safe handling of these materials in perspective with standard military explosives. The study is adding SSST testing results for a broad suite of different HMEs to the literature. Ultimately the study will suggest new guidelines and methods and possibly establish the SSST testing accuracies needed to develop safe handling practices for HMEs. Each participating testing laboratory uses identical test materials and preparation methods wherever possible. The testing performers involved are Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory (LANL), Indian Head Division, Naval Surface Warfare Center, (NSWC IHD), Sandia National Laboratories (SNL), and Air Force Research Laboratory (AFRL/RXQL). These tests are conducted as a proficiency study in order to establish some consistency in test protocols, procedures, and experiments and to compare results when these testing variables cannot be made consistent.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Integrated Data Collection Analysis (IDCA) Program - RDX Standard Data Set 2

The Integrated Data Collection Analysis (IDCA) program is conducting a proficiency study for Small- Scale Safety and Thermal (SSST) testing of homemade explosives (HMEs). Described here are the results for impact, friction, electrostatic discharge, and differential scanning calorimetry analysis of the RDX Type II Class 5 standard, from testing the second time in the Proficiency Test. This RDX testing (Set 2) compared to the first (Set 1) was found to have about the same impact sensitivity, have more BAM friction sensitivity, less ABL friction sensitivity, similar ESD sensitivity, and same DSC sensitivity.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Machine learning for continuous quantum error correction on superconducting qubits

Abstract Continuous quantum error correction has been found to have certain advantages over discrete quantum error correction, such as a reduction in hardware resources and the elimination of error mechanisms introduced by having entangling gates and ancilla qubits. We propose a machine learning algorithm for continuous quantum error correction that is based on the use of a recurrent neural network to identify bit-flip errors from continuous noisy syndrome measurements. The algorithm is designed to operate on measurement signals deviating from the ideal behavior in which the mean value corresponds to a code syndrome value and the measurement has white noise. We analyze continuous measurements taken from a superconducting architecture using three transmon qubits to identify three significant practical examples of non-ideal behavior, namely auto-correlation at temporal short lags, transient syndrome dynamics after each bit-flip, and drift in the steady-state syndrome values over the course of many experiments. Based on these real-world imperfections, we generate synthetic measurement signals from which to train the recurrent neural network, and then test its proficiency when implementing active error correction, comparing this with a traditional double threshold scheme and a discrete Bayesian classifier. The results show that our machine learning protocol is able to outperform the double threshold protocol across all tests, achieving a final state fidelity comparable to the discrete Bayesian classifier.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Savannah River National Laboratory Participation in the International Atomic Energy Agency CPC Interlaboratory Comparison Exercise 2

International Atomic Energy Agency Safeguards Analytical Services (IAEA-SGAS) oversees coordinating the second Controlled Potential Coulometry Quality Control Interlaboratory Comparison (CPC QC ILC) on behalf of the Nuclear Material Laboratory (NML). The purpose of the exercise is to: (1) verify the ability of participating laboratories to measure the Pu concentration in the sample solutions, and (2) estimate the method performance (repeatability and intermediate reproducibility). Sample shipping coordination was performed by IAEA-SGAS. The test sample is a plutonium nitrate solution (estimated molarity of 3-5 M), delivered in two PTFE screw-capped quartz ampoules. Each participating laboratory is to receive two ampoules. Each ampoule holds approximately 8 mL of solution containing approximately 10 mg Pu/g. The gross weights of the ampoules were provided. The test sample is assumed to have an iron content below the level of significance for the CPC. The isotopic composition of the plutonium test sample was provided; however, no analysis date was provided. In addition, IAEA-SGAS provided analytical instructions to participants. On September 20, 2022, SRNL received the samples sent by IAEA-SGAS.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗

Integrated Data Collection Analysis (IDCA) Program — RDX Standard Data Sets

The Integrated Data Collection Analysis (IDCA) program is conducting a proficiency study for Small- Scale Safety and Thermal (SSST) testing of homemade explosives (HMEs). Described here are the results for impact, friction, electrostatic discharge, and differential scanning calorimetry analysis of the RDX Type II Class 5 standard, for a third and fourth time in the Proficiency Test and averaged with the analysis results from the first and second time. The results, from averaging all four sets (1, 2, 3 and 4) of data suggest a material to have slightly more impact sensitivity, more BAM friction sensitivity, less ABL friction sensitivity, similar ESD sensitivity, and same DSC sensitivity, compared to the results from Set 1, which was used previously as the values for the RDX standard in IDCA Analysis Reports.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Integrated Data Collection Analysis (IDCA) Program - KClO 4 /Carbon Mixture

The Integrated Data Collection Analysis (IDCA) program is conducting a proficiency study for Small- Scale Safety and Thermal (SSST) testing of homemade explosives (HMEs). Described here are the results for impact, friction, electrostatic discharge, and differential scanning calorimetry analysis of a mixture of KClO 4 and activated carbon—KClO 4 /C mixture. This material was selected because of the challenge of performing SSST testing of a mixture of two solids. The mixture was found to be insensitive to impact, friction, and thermal stimulus, and somewhat sensitive to spark discharge. This effort, funded by the Department of Homeland Security (DHS), ultimately will put the issues of safe handling of these materials in perspective with standard military explosives. The study is adding SSST testing results for a broad suite of different HMEs to the literature. Ultimately the study has the potential to suggest new guidelines and methods and possibly establish the SSST testing accuracies needed to develop safe handling practices for HMEs. Each participating testing laboratory uses identical test materials and preparation methods wherever possible. Note, however, the test procedures differ among the laboratories. The results are compared among the laboratories and then compared to historical data from various sources. The testing performers involved for the KClO 4 /carbon mixture are Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory (LANL), Indian Head Division, Naval Surface Warfare Center, (NSWC IHD), and Air Force Research Laboratory (AFRL/RXQL). These tests are conducted as a proficiency study in order to establish some consistency in test protocols, procedures, and experiments and to understand how to compare results when these testing variables cannot be made consistent.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

TH-C-17A-01: Imaging Sensor Comparison for Real-Time Cherenkov Signal Detection From Tissue for Treatment Verification

Purpose: To identify the optimum imaging sensor for a clinical system that would provide real-time imaging of the surface beam profile on patients as novel visual information to radiation therapy technologists, and more rapidly collect clinical data for large-scale studies of Cherenkov applications in radiotherapy. Methods: Four camera types, CMOS, CCD, ICCD and EMICCD, were tested to determine proficiency in the detection of Cherenkov signal in the clinical radiotherapy setting, and subsequent maximum supportable frame rate. Where possible, time-gating between the trigger signal from the LINAC and the intensifiers was implemented to detect signal with room lighting conditions comparable to patient treatment scenarios. A solid water phantom was imaged by the EM-ICCD and ICCD to evaluate the minimum number of accumulations-on-chip required for adequate Cherenkov detection, defined as >200% electron counts per pixel over background signal. Additionally, an ICCD and EM-ICCD were used clinically to image patients undergoing whole-breast radiation therapy, to understand the impact of the resolution limitation of the EM-ICCD. Results: The intensifier-coupled cameras performed best at imaging Cherenkov signal, even with room lights on, which is essential for patient comfort. The tested EM-ICCD was able to support single-shot imaging and frame rates of 30 fps, however, the current maximum resolution of 512 × 512 pixels was restricting. The ICCD used in current clinical trials was limited to 4.7 fps at a 1024 × 1024 resolution. An intensifier with higher quantum efficiency at the entrance photocathode in the red wavelengths (30% QE vs current 7%) promises 16 fps at the same resolution at lower cost than the EM-ICCD. Conclusion: The ICCD with the better red wavelength QE intensifier was determined to be the best suited commercial-off-the-shelf camera to detect real-time Cherenkov signal and provide the best potential for real-time display of radiation dose on the skin during treatment. Funding is from grants from the NIH numbers R01CA109558 and R21EB017559.

60 APPLIED LIFE SCIENCES↗

Grout testing to support tank closure at the Savannah River Site - 15370

Final operational closure of the Savannah River Site (SRS) waste tanks is performed by filling the voids inside the tanks with a series of tailored grout formulas thereby stabilizing the remaining residuals. These tailored grout formulas were each developed to meet the demands of the closure process. The needs identified for the closure process include (1) a flowable, self-consolidating, reducing grout for tank fill, (2) a highly flowable grout capable of filling the 7-1/4 kilometers (4-1/2 miles) of 5-centimeter (2-inch) diameter cooling coils inside the tank, and (3) a highly flowable grout capable of filling equipment remaining in the tank. The specific characteristics of each of the grout formulations were tested to ensure they would function as required during implementation. Performance testing was also done on some of the grout formulations to confirm mix effectiveness and improve worker handling proficiency and conducted additional testing on the bulk fill grout to expand the placement capabilities of the grout. This paper focuses on the evolution of the closure process' identified needs, formulation development, and the subsequent testing of the tailored grout formulations utilized in the past tank closure processes at SRS. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Integrated Data Collection Analysis (IDCA) Program - NaClO 3 /Icing Sugar

The Integrated Data Collection Analysis (IDCA) program is conducting a proficiency study for Small- Scale Safety and Thermal (SSST) testing of homemade explosives (HMEs). Described here are the results for impact, friction, electrostatic discharge, and differential scanning calorimetry analysis of a mixture of NaClO 3 and icing sugar—NaClO 3 /icing sugar mixture. The mixture was found to: be more sensitive than RDX but less sensitive than PETN in impact testing (180-grit sandpaper); be more sensitive than RDX and about the same sensitivity as PETN in BAM fiction testing; be less sensitive than RDX and PETN except for one participant found the mixture more sensitive than PETN in ABL ESD testing; and to have one to three exothermic features with the lowest temperature event occurring at ~ 160°C always observed in thermal testing. Variations in testing parameters also affected the sensitivity.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Integrated Data Collection Analysis (IDCA) Program — Ammonium Nitrate

The Integrated Data Collection Analysis (IDCA) program is conducting a proficiency study for Small- Scale Safety and Thermal (SSST) testing of homemade explosives (HMEs). Described here are the results for impact, friction, electrostatic discharge, and differential scanning calorimetry analysis of ammonium nitrate (AN). AN was tested, in most cases, as both received from manufacturer and dried/sieved. The participants found the AN to be: 1) insensitive in Type 12A impact testing (although with a wide range of values), 2) completely insensitive in BAM friction testing, 3) less sensitive than the RDX standard in ABL friction testing, 4) less sensitive than RDX in ABL ESD testing, and 5) less sensitive than RDX and PETN in DSC thermal analyses.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Side effects of antimotion sickness drugs

The effects on operational proficiency of the antimotion sickness drugs scopolamine, promethazine and d-amphetamine are tested using a computerized pursuit meter. Proficiency is not significantly affected by oral doses of 0.25 mg or 0.50 mg scopolamine but is descreased by oral or I.M. doses of 25 mg promethazine. The performance decrement associated with 25 mg oral promethazine is prevented when combined with 10 mg oral d-amphetamine. The combination of 25 mg I.M. promethazine, 25 mg oral promethazine and 10 mg d-amphetamine produces less performance decrement than oral or I.M. doses of promethazine alone, though more performance decrement than a placebo. I.M. promethazine is adsorbed slowly and consequently may provoke drowsiness.

Wood, C. D.↗