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At least 19 records

Low responsiveness of machine learning models to critical or deteriorating health conditions

Machine learning (ML) based mortality prediction models can be immensely useful in intensive care units. Such a model should generate warnings to alert physicians when a patient’s condition rapidly deteriorates, or their vitals are in highly abnormal ranges. Before clinical deployment, it is important to comprehensively assess a model’s ability to recognize critical patient conditions. We develop multiple medical ML testing approaches, including a gradient ascent method and neural activation map. We systematically assess these machine learning models’ ability to respond to serious medical conditions using additional test cases, some of which are time series. Guided by medical doctors, our evaluation involves multiple machine learning models, resampling techniques, and four datasets for two clinical prediction tasks. We identify serious deficiencies in the models’ responsiveness, with the models being unable to recognize severely impaired medical conditions or rapidly deteriorating health. For in-hospital mortality prediction, the models tested using our synthesized cases fail to recognize 66% of the injuries. In some instances, the models fail to generate adequate mortality risk scores for all test cases. Our study identifies similar kinds of deficiencies in the responsiveness of 5-year breast and lung cancer prediction models. Using generated test cases, we find that statistical machine-learning models trained solely from patient data are grossly insufficient and have many dangerous blind spots. Most of the ML models tested fail to respond adequately to critically ill patients. How to incorporate medical knowledge into clinical machine learning models is an important future research direction.

60 APPLIED LIFE SCIENCES↗

Methods to Track Effective Doses from Airborne Radioactive Emissions for Compliance with 40 CFR 61, SUBPART H

US Department of Energy national laboratories can play an integral role in not only the advancement of science but also in the treatment of various medical conditions through research and development activities conducted at radioisotope production facilities. Here, a project has been underway at Oak Ridge National Laboratory since 2016 whose mission is to produce and supply the radioisotope 227 Ac, which is used in a radiopharmaceutical developed to treat certain types of prostate cancer and bone metastases. Production activities result in the environmental release of airborne radioactive emissions, which are governed by Clean Air Act regulations described in 40 CFR Part 61, Subpart H. Stack 3039, the source that emits radioactive effluents from 227 Ac production, is subject to additional requirements outlined in American National Standards Institute (ANSI) N13.1-1969 due to its grandfathered status. Radioactive emissions are limited to levels below those that would cause annual compliance dose standards for members of the public to be exceeded and stack 3039 to lose its grandfathered status. To allow for maximum production of 227 Ac without exceeding relevant dose limits, monthly tracking of project emissions and resulting CAP88-PC modeled effective doses to a maximally exposed individual have been implemented. Four years of tracking data were compiled and analyzed to identify additional methods that could be used to estimate project doses more frequently, potentially further optimizing 227 Ac production while maintaining compliance with applicable regulations.

atmospheric emissions↗

Draft Prototype Microreactor Transportation Safety Program

Microreactors are compact reactors capable of producing less than 50 megawatts of electrical energy. Typically, these reactors are factory-fabricated and designed to be easily transportable by truck, rail, vessel, or air. Microreactor designs often assume that the unit can be transported containing either unirradiated or irradiated fuel. The interest in microreactors is driven by several factors, including the need to generate power on at remote locations, at military installations, at facilities such as data centers, and in areas recovering from natural disasters. The U.S. Department of Defense is actively pursuing the microreactor concept to meet the increasing energy demands of military operations that require portable and dense power sources. Commercial vendors are also exploring microreactor concepts. The report Microreactor Transportation Emergency Planning Challenges (Maheras et al. 2024) outlined the emergency planning challenges associated with the transportation of microreactors by road, rail, and by barge/ship. The successful commercial deployment and redeployment of microreactors will also require the development of microreactor transportation safety programs. The elements in these safety programs are not specific to microreactors; however, the transport of microreactors may pose unique challenges in these areas. This report builds on the report Microreactor Transportation Emergency Planning Challenges (Maheras et al. 2024) and develops the elements of a prototype microreactor transportation safety program that describes the elements that should be contained vendor-developed microreactor transportation safety programs, identifying the unique elements associated with microreactor transport. This will provide vendors and their transportation contractors a basis for their transportation planning and will accelerate the commercial deployment and redeployment of microreactors by identifying those issues unique to microreactor transport. The emphasis of this report is on highway transport of microreactors. This is based on a U.S. Nuclear Regulatory Commission transportation package approval strategy of crawl-walk-run, where transport by highway is evaluated first (Coles et al. 2021, 2024, Maheras et al. 2021), then other surface modes (rail and barge/ship), and finally air transport. Evaluation of maritime transport of microreactors was recently initiated (Rigato et al. 2024, Maheras et al. 2025). The report first discusses microreactors in general and microreactor transportation safety program planning assumptions. The report then provides a description of the transportation safety planning process and provides an extensive discussion of the elements of transportation safety programs. Specific elements examined included transportation roles and responsibilities, transportation planning, transportation mode and route selection, carrier selection, transportation packaging, advance notification of shipments, public information and communications, emergency response plans and procedures, inspections, security, safe parking, shipment tracking, weather and road conditions, medical preparedness, training and exercises, and program evaluation. The report then identifies the unique elements of a transportation safety program associated with microreactor transport. These unique elements were in the areas of: the unusual nature of microreactor designs, compensatory measures, increased radiation dose rates in the vicinity of microreactors, transportation package approval versus 10 CFR 50.59, and the use of a risk-informed transportation package approval process.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Personalized, disease-stage specific, rapid identification of immunosuppression in sepsis

Introduction Data overlapping of different biological conditions prevents personalized medical decision-making. For example, when the neutrophil percentages of surviving septic patients overlap with those of non-survivors, no individualized assessment is possible. To ameliorate this problem, an immunological method was explored in the context of sepsis. Methods Blood leukocyte counts and relative percentages as well as the serum concentration of several proteins were investigated with 4072 longitudinal samples collected from 331 hospitalized patients classified as septic (n=286), non-septic (n=43), or not assigned (n=2). Two methodological approaches were evaluated: (i) a reductionist alternative, which analyzed variables in isolation; and (ii) a non-reductionist version, which examined interactions among six (leukocyte-, bacterial-, temporal-, personalized-, population-, and outcome-related) dimensions. Results The reductionist approach did not distinguish outcomes: the leukocyte and serum protein data of survivors and non-survivors overlapped. In contrast, the non-reductionist alternative differentiated several data groups, of which at least one was only composed of survivors (a finding observable since hospitalization day 1). Hence, the non-reductionist approach promoted personalized medical practices: every patient classified within a subset associated with 100% survival subset was likely to survive. The non-reductionist method also revealed five inflammatory or disease-related stages (provisionally named ‘early inflammation, early immunocompetence, intermediary immuno-suppression, late immuno-suppression, or other’). Mortality data validated these labels: both ‘suppression’ subsets revealed 100% mortality, the ‘immunocompetence’ group exhibited 100% survival, while the remaining sets reported two-digit mortality percentages. While the ‘intermediary’ suppression expressed an impaired monocyte-related function, the ‘late’ suppression displayed renal-related dysfunctions, as indicated by high concentrations of urea and creatinine. Discussion The data-driven differentiation of five data groups may foster early and non-overlapping biomedical decision-making, both upon admission and throughout their hospitalization. This approach could evaluate therapies, at personalized level, earlier. To ascertain repeatability and investigate the dynamics of the ‘other’ group, additional studies are recommended.

Immunology↗

A Field-Deployable Magnetic Resonance Imaging Rhizotron for Modeling and Enhancing Root Growth and Biogeochemical Function

A collaborative team from Texas A&M AgriLife Research, ABQMR Inc., the Soil Health Institute, the Athinoula A. Martinos Center for Biomedical Imaging, and NIST developed low-field magnetic resonance imaging (LF-MRI) instrumentation capable of imaging intact soil-root systems. The system measured root biomass, architecture, 3D mass distribution, and growth rates, providing a non-destructive means to evaluate ideal plant characteristics based on root metrics. It also successfully generated three-dimensional images of soil water content, a key property influencing root growth and exploration. Operating much like an MRI used in a medical setting, the system functioned in field conditions without damaging plants, overcoming the limitations of traditional methods such as trenching, soil coring, and root excavation. Over the course of the project, the team designed and built three functional prototype systems. These prototypes provided new insights into root–water–soil interactions that drive processes such as nutrient uptake, water use, and carbon management. This information contributed to efforts to optimize plants for carbon sequestration without sacrificing economic yield. The project also supported the identification of desirable traits for energy sorghum, including high root growth rates, more vertical root angles, and enhanced drought resilience under water-limiting conditions.

09 BIOMASS FUELS↗

Relativistic Laser Plasma Interactions At The Highest Intensities

High energy density science (HEDS) explores the nature of matter under extreme conditions of temperature and pressure. It is of fundamental importance and has many applications such as facilitating imaging with ions, neutrons, x-rays, and gamma rays with new applications being developed, including materials processing and medical therapies. In this project, we used high power, ultrashort pulse lasers to reach HEDS conditions. We have shown that low-cost, liquid crystal film based, double plasma mirror systems can be used to greatly improve laser pulse contrast while still maintaining high power and excellent spatial mode.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

CRISPRi functional genomics in bacteria and its application to medical and industrial research

SUMMARY Functional genomics is the use of systematic gene perturbation approaches to determine the contributions of genes under conditions of interest. Although functional genomic strategies have been used in bacteria for decades, recent studies have taken advantage of CRISPR (clustered regularly interspaced short palindromic repeats) technologies, such as CRISPRi (CRISPR interference), that are capable of precisely modulating expression of all genes in the genome. Here, we discuss and review the use of CRISPRi and related technologies for bacterial functional genomics. We discuss the strengths and weaknesses of CRISPRi as well as design considerations for CRISPRi genetic screens. We also review examples of how CRISPRi screens have defined relevant genetic targets for medical and industrial applications. Finally, we outline a few of the many possible directions that could be pursued using CRISPR-based functional genomics in bacteria. Our view is that the most exciting screens and discoveries are yet to come.

Microbiology↗

Macromolecular crystallography and biology at the Linac Coherent Light Source

The Linac Coherent Light Source (LCLS) has significantly impacted the field of biology by providing advanced capabilities for probing the structure and dynamics of biological molecules with high precision. The ultrashort coherent X-ray pulses from the LCLS have enabled ultrafast, time-resolved, serial femtosecond crystallography that is inaccessible at conventional synchrotron light sources. Since the facility's founding, scientists have captured detailed insights into biological processes at atomic resolution and fundamental timescales. The ability to observe these processes in real time and under conditions closely resembling their natural state is transforming our approach to studying biochemical mechanisms and developing new medical and energy applications. This work recounts some of the history of the LCLS, advances in biological research enabled by the LCLS, key biological areas that have been impacted and how the LCLS has helped to unravel complex biological phenomena in these fields.

59 BASIC BIOLOGICAL SCIENCES↗

Influence of background sources and topographic resolution in the Weather Research and Forecasting Model on xenon plume characteristics at monitoring stations

For many atmospheric monitoring applications, networks of measurement sites—such as the radionuclide stations of the International Monitoring System—can be sparse. With measurement locations potentially hundreds to thousands of kilometers from a release it is important to quantify the effects of physical processes on transport and dispersion of plumes between source and measurement locations. This study addresses the effects of background sources and topography resolution near the release location of radionuclides. We use the Weather Research and Forecasting (WRF) model with inline chemistry to investigate (1) how an additional, time-varying source of 133 Xe, such as an operational medical isotope production facility, contributes to activity concentration measurements at monitoring sites, and (2) how complex topography influences on atmospheric conditions near emission sources impact plume concentrations at varying distances from the source. Two 133 Xe emission sources, including (1) a high flux rate of short duration representing an explosive event, and (2) a variable and continuous background source, are simulated. The continuous background source contributes significantly to total 133 Xe concentrations at several monitoring stations. Further, a WRF simulation at 9 km horizontal resolution is compared with a nested grid simulation, where the innermost domain has a resolution of 1 km. Increased topographic resolution leads to an improved representation of plume responses to local winds, with topographic influences greatest at locations closest to the sources. Differences between the two domain resolutions decrease at greater distances from the sources, as plumes have time to spread and mix and are influenced by synoptic scale circulation patterns that are represented similarly in both simulations.

54 ENVIRONMENTAL SCIENCES↗

A comprehensive framework to assess elemental mercury in the Department of Energy: A time series analysis

Objective: This study investigated whether seasonal categories affect airborne mercury concentrations in the U.S. Department of Energy operations. Methods: We conducted an initial assessment of the general variability of airborne elemental mercury time-weighted average (TWA) samples. Then, we performed a two-component time series analysis to determine whether long-term, cyclical temperature change patterns affect mercury concentrations. Results: Both ARIMA time series models demonstrated stationary, non-random means (χ² = 83.8, p < 0.001) and standard deviation (χ² = 55.8, p < 0.001) of mercury concentrations. Here, our results indicate that the seasonal factors did not influence mercury concentration. Conclusions: Our results demonstrate that mercury concentrations primarily emanate from operational activities, work practices, and/or transient environmental conditions rather than seasonal fluctuations.

Cannady, Ryan T. [Oak Ridge National Laboratory (O↗

Designing Thermomechanically Stable Nanocrystalline Alloys for Low Friction and Wear: A Perspective

In this Perspective, we discuss recent work and future trends on the usage of thermomechanically stable and selflubricating nanocrystalline (NC) alloys for low friction and wear applications. The theoretical underpinnings and mechanistic framework for attaining and maintaining low friction and wear in metal contacts are presented. Initial work on stress, time, and temperature-dependent changes in friction and wear in NC alloys validates the models, demonstrating lower friction from decreased interfacial strength, contact pressure, sliding speed, and temperature and increased roughness and material hardness. Subsequent work reveals that NC Pt−Au, metal nitrides, complex-concentrated, and high-entropy alloys come with additional stabilization factors such as low-friction carbon tribofilms and oxide/amorphous−crystalline layers but are still susceptible to destabilization factors including irradiation and adverse environmental conditions.

alloys↗

Sulfur-functionalized solid-phase materials for the selective separation of arsenic and selenium

Radioactive arsenic (As) isotopes are of growing interest for applications in nuclear medicine, national security, and environmental research. Recent efforts at the Facility for Rare Isotope Beams (FRIB) have focused on aqueous harvesting of selenium-72,73 ( 72,73 Se) and their daughter isotopes, arsenic-72,73 ( 72,73 As), which are particularly valuable for medical applications and nuclear data studies, respectively. Both conventional isotope production and harvesting methods require chemical separations to purify radioactive As from parent and co-produced Se radioisotopes. While several solid-phase separation methods for As and Se exist, many depend on complex oxidation state control or highly acidic conditions. This study presents results for sulfur-based solid-phase materials selected to enable uptake at lower acidity and eliminate the need for intricate redox chemistry. Specifically, the performance of three covalently bound sulfur-based ligands were evaluated: (1) thiophenol-polystyrene, (2) propanethiol-silica, and (3) thiourea-silica. Uptake characteristics—including distribution coefficients (Dw), kinetics, and column separation behavior—were assessed using 75 Se and 73 As in hydrochloric (HCl) acid and nitric (HNO 3 ) solutions. The resins demonstrated high-yield (>95%) and high-purity As recovery across a range of HCl concentrations. Comparable results in HNO 3 were achieved when combined with anion exchange chromatography. Furthermore, the potential application of these materials for medical isotope generators was also investigated through ligand stability and repeated elution studies. Overall, sulfur leaching from the resins was negligible at the concentrations relevant for these separations but increased with higher acid concentrations.

Arsenic↗

Probing the limits of genetic recoding using multi-omics-guided evolution

Engineering the genetic code—by reassigning multiple of the 64 natural codons—enables making organisms resistant to all viruses, preventing genetic information exchange, and allowing the biosynthesis of genetically encoded unnatural polymers. However, synonymous codon replacement—recoding—is frequently lethal, and how recoding impacts fitness remains poorly explored. Here, we explore these effects using genome synthesis, directed evolution, and genome-transcriptome-translatome-proteome co-profiling on multiple synthetic Escherichia coli genomes. We construct six partially recoded E. coli strains bearing up to 45.8% of a synthetic genome with a deleterious 57-codon genetic code. As our analyses revealed widespread defects—including unassigned codons in Syn61 and Syn57—we apply multi-omics to revise our genome design and mitigate defects. Using multi-omics, we show that recoding induces transcriptional and translational changes leading to fitness defects under hundreds of conditions. Finally, we develop a multi-omics-guided evolution strategy that rapidly restores fitness, enabling genome synthesis with radical changes.

Nyerges, Akos [Harvard Medical School, Boston, MA ↗

Air-Stable Room-Temperature Quasi-2D Tin Iodide Perovskite Microlasers

Quasi-2D tin iodide perovskites (TIPs) are promising lead-free alternatives for optoelectronic applications, but achieving stable lasing remains challenging due to their limited environmental stability. Here, we report air-stable, room-temperature lasing from quasi-2D TIP microcrystals as small as 4 μm. Incorporation of the organic spacer 5IPA3 significantly enhanced the stability of these materials compared with previously reported TIPs. Lasing was observed from both dielectric (n = 4) and plasmonic (n = 3 and n = 4) TIP microlasers. Under picosecond pumping, lasing was sustained for over 108 pump pulses in ambient conditions. These results represent a significant step toward practical photonic applications of tin-based perovskites.

crystals↗

Documentation of Air Emissions Source Term for Radionuclide NESHAP Compliance: TA-53 Building 0984 Isotope Production Facility

This paper will document the air emissions source term for the TA-53 Building 0984 Isotope Production Facility (IPF). The facility has historically been managed as a minor source under Radionuclide NESHAP regulations, but began using a wider variety of irradiation targets and a higher beam current. To support expanded generation of actinium-225 for medical diagnostic and therapeutic uses, IPF is now irradiating thorium targets and the beam current is planned to increase from 250 microamperes up to 600 microamperes. These changes merit a review of the anticipated source term under the new proposed operational conditions. The end result of the review indicates the main stack (Exhaust Stack ES-1) needs to be managed as a major source with continuous emissions monitoring. No additional advance notifications or permitting is required as a result of these operational changes.

54 ENVIRONMENTAL SCIENCES↗

A review of criticality dosimetry at the Y-12 National Security Complex and practical importance of dose accuracy in emergency response

A nuclear criticality results in the emission of both neutron and gamma radiation and can produce doses to personnel near the event that exceed 0.1 Gy (10 rad). The primary purpose of nuclear accident dosimetry is to rapidly identify affected personnel in need of prompt medical treatment and to reassure personnel who have been only minimally exposed. While accurate dosimetry is desired, it must be recognized that dose determinations made from whole-body dosimeters or simple triage methods are very rough estimates and contain significant uncertainties. Even when accounting for factors like varying neutron energy spectra, mean photon energies, body orientation within the radiation field, and transient effects on dosimeter response, etc., the end value is a dosimetric quantity defined for very specific radiological conditions and determined within a simple phantom usually at a single depth. Of more importance is the biological response to the radiation, which will vary by person and can be affected by the individual’s radiation sensitivity, age, gender, mass, and underlying health conditions. The overall biological, person-specific response to a given dose cannot be precisely determined except by patient symptom observation and individual biological dosimetry (e.g. chromosome analysis, lymphocyte ratios, etc.). This work describes and discusses the criticality accident dosimetry program at the Y-12 National Security Complex, a United States Department of Energy National Nuclear Security Administration facility. In conclusion, the primary goals of the Y-12 accident dosimetry program are, among others, the rapid identification of significantly exposed persons, prompt routing of exposed workers for medical evaluation and treatment, and the ultimate processing of dosimeters to assign doses to personnel.

61 RADIATION PROTECTION AND DOSIMETRY↗

Laser-initiated p – 11 B fusion reactions in petawatt high-repetition-rate laser facilities

Driving of the nuclear fusion reaction p + 11 B → 3α + 8.7 MeV under laboratory conditions by interaction between high-power laser pulses and matter has become a popular field of research, owing to its numerous potential applications: as an alternative to deuterium–tritium for fusion energy production, astrophysics studies, and alpha-particle generation for medical treatment. One possible scheme for laser-driven p– 11 B reactions is to direct a beam of laser-accelerated protons onto a boron (B) sample (the so-called “pitcher-catcher” scheme). This technique has been successfully implemented on large high-energy lasers, yielding hundreds of joules per shot at low repetition. We present here a complementary approach, exploiting the high repetition rate of the VEGA III petawatt laser at CLPU (Spain), aiming at accumulating results from many interactions at much lower energy, to provide better control of the parameters and the statistics of the measurements. Despite a moderate energy per pulse, our experiment allowed exploration of the laser-driven fusion process with tens (up to hundreds) of laser shots. The experiment provided a clear signature of the reactions involved and of the fusion products, accumulated over many shots, leading to an improved optimization of the diagnostics for experimental campaigns of this type. In this paper, we discuss the effectiveness of laser-driven p– 11 B fusion in the pitcher–catcher scheme, at a high repetition rate, addressing the challenges of this experimental scheme and highlighting its critical aspects. Our proposed methodology allows evaluation of the performance of this scheme for laser-driven alpha particle production and can be adapted to high-repetition-rate laser facilities with higher energy and intensity.

Alpha particles↗

Investigating the role of adipose tissue in mobility and aging: design and methods of the Adipose Tissue ancillary to the Study of Muscle, Mobility, and Aging (SOMMA-AT)

Background Age-related changes in adipose tissue affect chronic medical diseases and mobility disability but mechanism remains poorly understood. The goal of this study is to define methods for phenotyping unique characteristics of adipose tissue from older adults. Methods Older adults enrolled in study of muscle, mobility, and aging selected for the adipose tissue ancillary (SOMMA-AT; N = 210, 52.38% women, 76.12 ± 4.37 years) were assessed for regional adiposity by whole-body magnetic resonance (AMRA) and underwent a needle-aspiration biopsy of abdominal subcutaneous adipose tissue (ASAT). ASAT biopsies were flash frozen, fixed, or processed for downstream applications and deposited at the biorepository. Biopsy yields, qualitative features, adipocyte sizes, and concentration of adipokines secreted in ASAT explant conditioned media were measured. Inter-measure Spearman correlations were determined. Results Regional, but not total, adiposity differed by sex: women had greater ASAT mass (8.20 ± 2.73 kg, p < .001) and biopsy yield (3.44 ± 1.81 g, p < .001) than men (ASAT = 5.95 ± 2.30 kg, biopsy = 2.30 ± 1.40 g). ASAT mass correlated with leptin (r = 0.54, p < .001) and not resistin (p = .248) and adiponectin (p = .353). Adipocyte area correlated with ASAT mass (r = 0.34, p < .001), BMI (r = 0.33, p < .001), adiponectin (r = −0.22, p = .005) and leptin (r = 0.18, p = .024) but not with resistin (p = .490). Conclusion In addition to the detailed ASAT biopsy processing in this report, we found that adipocyte area correlated with ASAT mass, and both measures related to some key adipokines in the explant conditioned media. In conclusion, these results, methods, and biological repositories underscore the potential of this unique cohort to impact the understanding of aging adipose biology on disease, disability, and other aging tissues.

60 APPLIED LIFE SCIENCES↗