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Urbanization may enhance tornado potential: A single case report

Tornadoes pose a risk of catastrophic economic loss and casualty in the United States. Modification of land use by urbanization alters the meteorological conditions that may impact tornado formation and intensification processes. Here we explored the simulated impact of Kansas City urbanization on the tornado potential of a supercell storm. In this studied case, we found that urbanization might enhance tornado potential by a) strengthening the low-level streamwise vorticity in the storm inflow region, thus forming stronger rotating updrafts; and b) intensifying near-surface horizontal vorticity near the boundary of the forward-flank cold pool which increases the ingestion, tilting, and stretching of streamwise horizontal vorticity into vertical vorticity. The former results from the stronger east-to-west pressure perturbation gradient due to the faster, stronger outflow boundary, and the latter is mainly a result of stronger cold fronts and a better alignment of storm-relative inflow with the horizontal vorticity vector. We emphasize that our conclusions only represent one possibility of how urbanization would affect tornado potential, and a more systematic examination is needed to achieve a more general conclusion.

54 ENVIRONMENTAL SCIENCES↗

Shock Damage Analysis in Serial Femtosecond Crystallography Data Collected at MHz X-ray Free-Electron Lasers

Serial femtosecond crystallography (SFX) data were recorded at the European X-ray free-electron laser facility (EuXFEL) with protein microcrystals delivered via a microscopic liquid jet. An XFEL beam striking such a jet may launch supersonic shock waves up the jet, compromising the oncoming sample. To investigate this efficiently, we employed a novel XFEL pulse pattern to nominally expose the sample to between zero and four shock waves before being probed. Analyzing hit rate, indexing rate, and resolution for diffraction data recorded at MHz pulse rates, we found no evidence of damage. Notably, however, this conclusion could only be drawn after careful identification and assimilation of numerous interrelated experimental factors, which we describe in detail. Failure to do so would have led to an erroneous conclusion. Femtosecond photography of the sample-carrying jet revealed critically different jet behavior from that of all homogeneous liquid jets studied to date in this manner.

36 MATERIALS SCIENCE↗

Effects of small marine energy deployments on oceanographic systems

The placement and operation of marine energy deployments in the ocean have the potential to change flow patterns, decrease wave heights, and/or remove energy from the oceanographic system. Changes in oceanographic systems resulting from harvesting marine energy, particularly tidal and wave energy, may be of concern. These changes include alterations in nearfield and farfield physical processes, as well as potential secondary environmental effects such as changes in sediment transport patterns, biological processes, or coastal erosion. Knowledge of changes in oceanographic systems associated with marine energy is primarily available from numerical modeling studies, informed by some laboratory tests and very few field measurements. A literature review was conducted using the Tethys knowledge base and other online sources, building on conclusions from the Ocean Energy Systems-Environmental State of the Science report. Potential changes in oceanographic systems that may be caused by marine energy differ between tidal and wave devices because of different extraction mechanisms and siting locations. Numerical models show that tidal extraction on the order of hundreds of megawatts or with significant channel blockage is required to create changes in oceanographic processes that exceed natural variability. Effects from wave energy extraction in arrays are localized and dependent on array spacing and proximity to the shore. Here the available evidence supports the conclusion that the risk of significant environmental effects from such changes could be retired (i.e., less investigation required for every project) for small deployments—those representative of the state of the industry in 2021. Determining changes in oceanographic systems to be low risk for small deployments can thereby streamline environmental consenting by reducing monitoring needs at this early stage in the industry.

54 ENVIRONMENTAL SCIENCES↗

SDSS J1058+5443: A Blue Quasar without Optical/NUV Broad Emission Lines

In this paper, the blue quasar SDSS J105816.19+544310.2 (=SDSS J1058+5443) at redshift 0.479 has been reported as the best true type 2 quasar candidate with the disappearance of central broad-line regions. There are no definite conclusions on the very existence of true type 2 active galactic nuclei (AGN), mainly due to detected optical broad emission lines in high-quality spectra of some previously classified true type 2 AGN candidates. Here, unlike previously reported true type 2 AGN candidates among narrow emission-line galaxies with weak AGN activities but strong stellar lights, the definitely blue quasar SDSS J1058+5443 can be well confirmed as a true type 2 quasar due to apparent quasar-shape blue continuum emissions but an apparent loss of both the optical broad Balmer emission lines and the near-UV (NUV) broad Mg II emission line. Based on different model functions and the F-test statistical technique, after considering blueshifted optical and UV Fe II emissions, there are no apparent broad optical Balmer emission lines and/or broad NUV Mg II lines, and the confidence level is smaller than 1σ in support of broad optical and NUV emission lines. Moreover, assuming the virialization assumption to broad-line emission clouds, the reconstructed broad emission lines strongly indicate that the probable intrinsic broad emission lines, if they exist, cannot be hidden or overwhelmed in the noise of the Sloan Digital Sky Survey spectrum of SDSS J1058+5443. Therefore, SDSS J1058+5443 is so far the best and most robust true type 2 quasar candidate, leading to the clear conclusion of the very existence of true type 2 AGN.

79 ASTRONOMY AND ASTROPHYSICS↗

The z ∼ 1.03 Merging Cluster SPT-CL J0356–5337: New Strong Lensing Analysis with HST and MUSE

We present a strong lensing analysis and reconstruct the mass distribution of SPT-CL J0356−5337, a galaxy cluster at redshift z = 1.034. Our model supersedes previous models by making use of new multiband Hubble Space Telescope data and Multi-Unit Spectroscopic Explorer (MUSE) spectroscopy. We identify two additional lensed galaxies to inform a more well-constrained model using 12 sets of multiple images in five separate lensed sources. The three previously known sources were spectroscopically confirmed by G. Mahler et al. at redshifts of z = 2.363, z = 2.364, and z = 3.048. We measured the spectroscopic redshifts of two of the newly discovered arcs using MUSE data, at z = 3.0205 and z = 5.3288. We increase the number of cluster member galaxies by a factor of 3 compared to previous work. We also report the detection of extended Lyα emission from several background galaxies. We measure the total projected mass density of the two major subcluster components, one dominated by the brightest cluster galaxy and the other by a compact group of luminous red galaxies. We find ${M}_{{\rm{B}}{\rm{C}}{\rm{G}}}(\lt 80\,\rm{kpc})=3.9{3}_{-0.14}^{+0.21}\times 1{0}^{13}$ M⊙ and ${M}_{{\rm{LRG}}}(\lt 80\,\rm{kpc})=2.9{2}_{-0.23}^{+0.16}\times 1{0}^{13}$ M⊙, yielding a mass ratio of $1.3{5}_{-0.08}^{+0.16}$ . The strong lensing constraints offer a robust estimate of the projected mass density regardless of modeling assumptions; allowing more substructure in this line of sight does not change the results or conclusions. Our results corroborate the conclusion that SPT-CL J0356−5337 is dominated by two mass components and is likely undergoing a major merger on the plane of the sky.

79 ASTRONOMY AND ASTROPHYSICS↗

Turbulence in Core-collapse Supernovae

It is understood in a general sense that turbulent fluid motion below the shock front in a core-collapse supernova stiffens the effective equation of state of the fluid and aids in the revival of the explosion. However, when one wishes to be precise and quantify the amount of turbulence in a supernova simulation, one immediately encounters the problem that turbulence is difficult to define and measure. Using the 3D magnetohydrodynamic code ELEPHANT, we study how different definitions of turbulence change one’s conclusions about the amount of turbulence in a supernova and the extent to which it helps the explosion. We find that, while all the definitions of turbulence we use lead to a qualitatively similar growth pattern over time of the turbulent kinetic energy in the gain region, the total amount of turbulent kinetic energy, and especially the ratios of turbulent to total kinetic energy, distinguish them. Some of the definitions appear to indicate turbulence is a necessary contributor to the explosion, and others indicate it is not. The different definitions also produce turbulence maps with different correlations with maps of the enstrophy, a quantity widely regarded as also indicating the presence of turbulence. We also compute the turbulent adiabatic index and observe that, in regions of low enstrophy, this quantity is sensitive to the definition used. As a consequence, the effective adiabatic index depends upon the method used to measure the turbulence, and thus it alters one’s conclusions regarding the impact of turbulence within the supernova.

computational astronomy↗

Safe Operations at Roadway Junctions - Design Principles from Automated Guideway Transit

Herein this paper describes a system-level view of a fully automated transit system comprising a fleet of automated vehicles (AVs) in driverless operation, each with an SAE level 4 Automated Driving System, along with its related safety infrastructure and other system equipment. This AV system-level control is compared to the automatic train control system used in automated guideway transit technology, particularly that of communications-based train control (CBTC). Drawing from the safety principles, analysis methods, and risk assessments of CBTC systems, comparable functional subsystem definitions are proposed for AV fleets in driverless operation. With the prospect of multiple AV fleets operating within a single automated mobility district, the criticality of protecting roadway junctions requires an approach like that of automated fixed-guideway transit systems, in which a guideway switch zone "interlocking" at each junction location deconflicts railway traffic, affirming safe passage. The analogous AV protection safety subsystem is defined as fail-safe equipment that monitors roadway intersections and junctions, communicates traffic signal status, perceives and communicates alerts and signals to AV connected vehicles concerning potential unsafe conditions, and performs related primary safety functions. Conclusions are drawn that the AV protection roadway intersection functions must be performed by local roadside equipment dedicated to protecting each roadway intersection and junction. Further, it is concluded that the communications technology connecting the infrastructure with the vehicle to perform this vital, fail-safe protection should meet specific functional and performance criteria.

33 ADVANCED PROPULSION SYSTEMS↗

Evaluating 3 decades of precipitation in the Upper Colorado River basin from a high-resolution regional climate model

Abstract. Convection-permitting regional climate models (RCMs) have recently become tractable for applications at multi-decadal timescales. These types of models have tremendous utility for water resource studies, but better characterization of precipitation biases is needed, particularly for water-resource-critical mountain regions, where precipitation is highly variable in space, observations are sparse, and the societal water need is great. This study examines 34 years (1987–2020) of RCM precipitation from the Weather Research and Forecasting model (WRF; v3.8.1), using the Climate Forecast System Reanalysis (CFS; CFSv2) initial and lateral boundary conditions and a 1 km × 1 km innermost grid spacing. The RCM is centered over the Upper Colorado River basin, with a focus on the high-elevation, 750 km2 East River watershed (ERW), where a variety of high-impact scientific activities are currently ongoing. Precipitation is compared against point observations (Natural Resources Conservation Service Snow Telemetry or SNOTEL), gridded climate datasets (Newman, Livneh, and PRISM), and Bayesian reconstructions of watershed mean precipitation conditioned on streamflow and high-resolution snow remote-sensing products. We find that the cool-season precipitation percent error between WRF and 23 SNOTEL gauges has a low overall bias (x^ = 0.25 %, s = 13.63 %) and that WRF has a higher percent error during the warm season (x^ = 10.37 %, s = 12.79 %). Warm-season bias manifests as a high number of low-precipitation days, though the low-resolution or SNOTEL gauges limit some of the conclusions that can be drawn. Regional comparisons between WRF precipitation accumulation and three different gridded datasets show differences on the order of ± 20 %, particularly at the highest elevations and in keeping with findings from other studies. We find that WRF agrees slightly better with the Bayesian reconstruction of precipitation in the ERW compared to the gridded precipitation datasets, particularly when changing SNOTEL densities are taken into account. The conclusions are that the RCM reasonably captures orographic precipitation in this region and demonstrates that leveraging additional hydrologic information (streamflow and snow remote-sensing data) improves the ability to characterize biases in RCM precipitation fields. Error characteristics reported in this study are essential for leveraging the RCM model outputs for studies of past and future climates and water resource applications. The methods developed in this study can be applied to other watersheds and model configurations. Hourly 1 km × 1 km precipitation and other meteorological outputs from this dataset are publicly available and suitable for a wide variety of applications.

Geology↗

Results from an International Interlaboratory Study on Light- and Elevated Temperature-Induced Degradation (LETID) in Solar Modules

This presentation reports recently submitted results from an international interlaboratory comparison study on light- and elevated temperature-induced degradation (LETID) on crystalline silicon photovoltaic (PV) modules. A large global network of PV module manufacturers and PV testing laboratories collaborated to design a protocol for LETID detection, and screen a large and diverse set of prototype modules for LETID. We summarize the range of observed degradation and provide initial conclusions on the reproducibility of results across labs. In LETID-sensitive modules, both open-circuit voltage (VOC) and short-circuit current (ISC) degrade by a roughly similar magnitude. We observe, as do previous studies, that LETID affects each cell in a module differently. An investigation of the potential mismatch losses caused by nonuniform LETID degradation found that mismatch loss is insignificant compared to the direct LETID-related losses. We summarize the conclusions drawn from the study, provide an update on a forthcoming standard technical specification for LETID testing of PV modules (IEC TS 63342 ED1), and discuss unresolved questions and potential future work on LETID in PV modules.

degradation↗

Timelike Compton Scattering from a longitudinally polarised target with CLAS12 at Jefferson Lab

Explorations into the internal dynamics of hadrons are constantly evolving, and the requirement for experimental results to verify theoretical models of hadron structure is paramount. A key area in this field is the study of Generalised Parton Distributions (GPDs), which are functions used to model the momenta of quarks and gluons within hadrons, and the methods to access GPDs experimentally. One such scattering process that allows access to these is Timelike Compton Scattering. TCS complements existing Deeply Virtual Compton Scattering experiments and allows investigation into the universality of GPDs through access to the real and imaginary parts of the parton helicity independent GPD Hq via beam spin asymmetries (BSA), and it provides novel access to the real and imaginary parts of the parton helicity dependent GPD ˜Hq through target polarisation asymmetries (TSA). This thesis work presents a comparative study with the first published BSA for TCS at the Thomas Jefferson National Accelerator Facility (JLab), alongside a first time extraction of a Target Spin Asymmetry with the Summer 2022 data taking run. JLab hosts the Continuous Electron Beam Accelerator Facility (CEBAF) which provides a 12 GeV electron beam to four experimental halls. Hall-B contains the CEBAF Large Acceptance Spectrometer, which took data across three run periods on a longitudinally polarised NH3 and ND3 fixed target from 2022-2023, to extract measurements of electron-proton scattering, from which a TCS signal could be extracted. The thesis discusses work done to understand and eliminate contributions from the non-/low-polarised nuclear background, testing pre-established cuts to eliminate pion background from a dilepton (e+e-) final state and modifying them as needed for the new experimental run, and attempts to hone in on a clean TCS signal from which to extract the two asymmetry observables. A comparison with existing BSA results was performed; however, the statistical errors are too large to draw a significant conclusion as to whether there is agreement across each bin. More data is needed for a multidimensionally binned extraction. A proof of principle was achieved in the TSA measurements, with two out of four kinematic bins showing preliminary agreement in shape with theoretical values. Again, the errors are significant due to the contributions from the nuclear background. To support these conclusions, a further study was done, which takes into account an estimate of the asymmetries with the full available dataset (this thesis is based only on data taken in the summer set; at the time of writing processing was still being conducted for the final two datasets), as well as an estimate including additional future experiment days that were awarded in July 2024. Additional work was done on a secondary project exploring the feasibility of measuring TCS at the upcoming Electron Ion Collider, supporting the design proposal for the detector for the first interaction region and giving a positive outlook for the future of these types of measurements beyond JLab.

Gates, Kayleigh [Univ. of Glasgow, Scotland (Unite↗

Select Proliferation Studies on TRISO-fueled, Heat-Pipe-cooled Microreactors

Nuclear microreactors carry the potential to open up new markets for the nuclear industry, as their expected cost competitiveness in non-traditional market segments (e.g., mines, military bases, extraterrestrial surfaces, and remote areas), and their inherent safety features make them deployable when other power sources are unavailable or difficult to exploit. For countries that have not traditionally participated in nuclear power, microreactors represent a clean energy solution [1]. However, their use, especially in non-weapons states, may entail challenges in terms of maintaining international nuclear safeguards [2]. Furthermore, the deployment locations where microreactors may prove most cost competitive would be difficult to access by state and International Atomic Energy Agency (IAEA) inspectors [3]. In addition to the isolated nature of potential deployment sites, the low-power characteristic of microreactors suggests that numerous microreactors would need to be deployed to meet energy demands. That, coupled with the unique physics of many current microreactor designs, opens up a new area of research with respect to nonproliferation and safeguards concerns [2]. Whereas traditional facilities are inspected as isolated cases when looking for signs of diversion or misuse; microreactors may need to be assessed in the context of the entire fleet to which they belong. International safeguards necessitate timely detection of any significant quantities (SQs) of material that are being diverted (e.g., 1 SQ of special nuclear material diverted over the course of a 1-year period) [4]. For low-enriched uranium, the IAEA defines 1 SQ as corresponding to 75 kg of 235U. The purpose of the present paper is to explore the detectability threshold for material diversion in microreactors by relying on critical control drum angles, excess reactivity, and the reactor lifetime as the selected operational parameters. For this assessment, a heat-pipe-cooled microreactor was regarded as the base design. While the conclusions reached in this paper are not readily extendable to the design of actual microreactors, the analysis herein enables conclusions to be drawn regarding the level of accuracy needed for reference calculations in order to detect diversion scenarios by utilizing the selected operational parameters (i.e., mainly control drum angles, critical insertion angle, and the reactor lifetime).

22 - GENERAL STUDIES OF NUCLEAR REACTORS↗

DOE CESER 6 GHz Interference Study

DOE CESER has sponsored Idaho National Laboratory (INL) to conduct an objective and independent study of potential 6 GHz interference from outdoor operation of unlicensed devices in the 6 GHz band on fixed service (FS) microwave communication links operated by electrical sector incumbents in that band. INL is collaborating with University of Notre Dame (UND), Electric Power Research Institute (EPRI), Lockard & White, Southern Company, and AT&T, to gather data with real-world 6 GHz interference experiments and identify (1) the potential for interference from unlicensed devices and (2) the interference necessary to cause harm to the incumbents. In addition to the functional assessment, a security assessment of the FCC mandated Automatic Frequency Coordination (AFC) System to regulate use of unlicensed 6 GHz standard power devices is also being conducted. A major objective is to create a science-based and defensible methodology used to produce the necessary data and to derive objective conclusions. This proven methodology can then be used to produce objective data and conclusions for other spectrum bands with similar incumbent uses including 4.4 – 4.9 GHz and 7.125 – 7.4 GHz, identified in the reconciliation bill that was adopted on July 4, 2025, as well as the National Spectrum Strategy discussions that are ongoing. This report contains 6 GHz field experiments and findings in the following real-world scenarios with commercial unlicensed standard power (SP) 6 GHz devices regulated by Automated Frequency Coordination (AFC): • University of Notre Dame (UND) Stadium with a capacity of 80,000 spectators, where Wi-Fi operating in 6 GHz has been deployed recently • Southern Company 6 GHz FS microwave link between Columbus and Fortson, Georgia Following are the following key findings from this study. 1. The AFC is under-protective of FS when line-of-sight exists along the path centerline. Data collected at Southern’s 6 GHz fixed link site shows significant erosion of as much as 21.4-24.4 dB of under-protection that can lead to potential service degradation under typical operating conditions. This first key finding is most likely the result of erroneous use of the RF propagation model. INL will collaborate with EPRI and the AFC Functional Requirements Working Group to submit a change request to the WinnForum TS-1014 standard towards correct use of the propagation model by the AFC. 2. There is additive interference effect of about 3 dB from nearly equal power interferers measured from simultaneous operation of two SP AP's operating co-channel with the FS receive from different locations along the path. This second key finding should be used to add the impact of additive interference of operation of multiple APs in the same geographical area, to the next generation of AFCs. INL will collaborate with FCC on the need for the AFC to consider additive interference. We also recommend that additional experiments are conducted on 6 GHz spectrum interference to further improve the AFC operation as the number of outdoor Wi-Fi devices continues to increase. These proposed steps and recommendations will make the co-existence of the incumbents and the 6 GHz outdoor Wi-Fi providers possible without any impact on the incumbents with a win-win outcome for all.

6 GHz↗

A study of examiner accuracy in cartridge case comparisons. Part 1: Examiner error rates

This report describes a study undertaken to estimate examiner (not laboratory) error rates for false Identifications and false Eliminations when comparing an unknown to a collection of three known cartridge cases. Volunteer active examiners with Association of Firearm and Toolmark Examiners (AFTE) membership or working in laboratories that participate in the Association of Crime Laboratory Directors (ASCLD) were provided with 15 sets of three known and one questioned cartridge cases fired from a collection of 25 new Ruger SR9 handguns. Remington 9-mm Luger (manufacturer designation L9MM3) ammunition was used and comparison sets were made up of cartridge cases fired within 100 cartridges of each other for each gun. Examiners were provided with a background survey, an answer sheet allowing for the AFTE Range of Conclusions, and return shipping materials. In addition to determining whether the known and questioned cartridge cases were fired with the same handgun, examiners were also asked to assess how many of the three knowns in each set were suitable for comparison, providing an estimated rate of how often each firearm used in the study produces useable, quality marks. The participating examiners were provided with both same-source and different-source comparison sets allowing the study to assess both error rates. Responses were received from 218 participating examiners. The overall rate of false Eliminations was estimated as 0.367% from comparisons known to be from the same firearm but reported as Eliminations. The overall rate of false Identifications was estimated as 1.01% from comparisons known to be from different firearms but reported as Identifications. The rates are not uniform across the sample population with a few examiners providing most of the false Identification responses. Rates of poor-quality mark production varied across the 25 sample handguns; those rates were 2.3% (±1.4%). Both false Elimination and false Identification rates are comparable to or lower than the rate of production of poor-quality marks by the firearms used in this study.

99 GENERAL AND MISCELLANEOUS↗

State Policies on Access to Vaccination Services for Low-Income Adults

Importance State vaccination benefits coverage and access for adult Medicaid beneficiaries vary substantially. Multiple studies have documented lower vaccination uptake in publicly insured adults compared with privately insured adults. Objective To evaluate adult Medicaid beneficiaries’ access to adult immunization services through review of vaccination benefits coverage in Medicaid programs across the 50 states and the District of Columbia. Design, Setting, and Participants A public domain document review with supplemental semistructured telephone survey was conducted between June 1, 2018, and June 14, 2019, to evaluate vaccination services benefits in fee-for-service and managed care organization arrangements for adult Medicaid beneficiaries in the 50 states and the District of Columbia (total, 51 Medicaid programs). Exposures Document review of benefits coverage for adult immunization services and supplemental survey with validation of document review findings. Main Outcomes and Measures Benefits coverage for adult Medicaid beneficiaries and reimbursement amounts for vaccine purchase and administration. Results Public domain document review was completed for all 51 jurisdictions. Among these, 44 Medicaid programs (86%) validated document review findings and completed the survey. Only 22 Medicaid programs (43%) covered all 13 Advisory Committee on Immunization Practices–recommended adult immunizations under both fee-for-service and managed care organization arrangements. Most fee-for-service arrangements (37 of 49) reimbursed health care professionals using any of the 4 approved vaccine administration codes; however, 8 of 49 programs did not separately reimburse for vaccine administration to adult Medicaid beneficiaries. Depending on administration route, median reimbursement for adult vaccine administration ranged from $\$9.81$ to $\$13.98$ per dose. Median per-dose reimbursement for adult vaccine purchase was highest for 9-valent human papillomavirus vaccine ($\$204.87$) and lowest for Haemophilus influenzae type b vaccine ($\$18.09$). Median reimbursement was below the private sector price for 7 of the 13 included vaccines. Conclusions and Relevance Even in programs with complete vaccination benefits coverage, reimbursement amounts to health care professionals for vaccine purchase and administration may not fully cover vaccination provision costs. Reimbursement amounts below costs may reduce incentives for health care professionals to vaccinate low-income adults and thereby limit Medicaid adult beneficiary access to vaccination.

60 APPLIED LIFE SCIENCES↗

Cancer Incidence Trends in Successive Social Generations in the US

Importance: The incidence of some cancers in the US is increasing in younger age groups, but underlying trends in cancer patterns by birth year remain unclear. Objective: To estimate cancer incidence trends in successive social generations. Design, Setting, and Participants: In this cohort study, incident invasive cancers were ascertained from the Surveillance, Epidemiology, and End Results (SEER) program’s 13-registry database (November 2020 submission, accessed August 14, 2023). Invasive cancers diagnosed at ages 35 to 84 years during 1992 to 2018 within 152 strata were defined by cancer site, sex, and race and ethnicity. Exposure: Invasive cancer. Main Outcome and Measures: Stratum-specific semiparametric age-period-cohort (SAGE) models were fitted and incidence per 100 000 person-years at the reference age of 60 years was calculated for single-year birth cohorts from 1908 through 1983 (fitted cohort patterns [FCPs]). The FCPs and FCP incidence rate ratios (IRRs) were compared by site for Generation X (born between 1965 and 1980) and Baby Boomers (born between 1946 and 1964). Results: A total of 3.8 million individuals with invasive cancer (51.0% male; 8.6% Asian or Pacific Islander, 9.5% Hispanic, 10.4% non-Hispanic Black, and 71.5% non-Hispanic White) were included in the analysis. In Generation X vs Baby Boomers, FCP IRRs among women increased significantly for thyroid (2.76; 95% CI, 2.41-3.15), kidney (1.99; 95% CI, 1.70-2.32), rectal (1.84; 95% CI, 1.52-2.22), corpus uterine (1.75; 95% CI, 1.40-2.18), colon (1.56; 95% CI, 1.27-1.92), and pancreatic (1.39; 95% CI, 1.07-1.80) cancers; non-Hodgkins lymphoma (1.40; 95% CI, 1.08-1.82); and leukemia (1.27; 95% CI, 1.03-1.58). Among men, IRRs increased for thyroid (2.16; 95% CI, 1.87-2.50), kidney (2.14; 95% CI, 1.86-2.46), rectal (1.80; 95% CI, 1.52-2.12), colon (1.60; 95% CI, 1.32-1.94), and prostate (1.25; 95% CI, 1.03-1.52) cancers and leukemia (1.34; 95% CI, 1.08-1.66). Lung (IRR, 0.60; 95% CI, 0.50-0.72) and cervical (IRR, 0.71; 95% CI, 0.57-0.89) cancer incidence decreased among women, and lung (IRR, 0.51; 95% CI, 0.43-0.60), liver (IRR, 0.76; 95% CI, 0.63-0.91), and gallbladder (IRR, 0.85; 95% CI, 0.72-1.00) cancer and non-Hodgkins lymphoma (IRR, 0.75; 95% CI, 0.61-0.93) incidence decreased among men. For all cancers combined, FCPs were higher in Generation X than for Baby Boomers because gaining cancers numerically overtook falling cancers in all groups except Asian or Pacific Islander men. Conclusions and Relevance: In this model-based cohort analysis of incident invasive cancer in the general population, decreases in lung and cervical cancers in Generation X may be offset by gains at other sites. Generation X may be experiencing larger per-capita increases in the incidence of leading cancers than any prior generation born in 1908 through 1964. On current trajectories, cancer incidence could remain high for decades.

60 APPLIED LIFE SCIENCES↗

Agent-Based Model of Combined Community- and Jail-Based Take-Home Naloxone Distribution

Importance Opioid-related overdose accounts for almost 80 000 deaths annually across the US. People who use drugs leaving jails are at particularly high risk for opioid-related overdose and may benefit from take-home naloxone (THN) distribution. Objective To estimate the population impact of THN distribution at jail release to reverse opioid-related overdose among people with opioid use disorders. Design, Setting, and Participants This study developed the agent-based Justice-Community Circulation Model (JCCM) to model a synthetic population of individuals with and without a history of opioid use. Epidemiological data from 2014 to 2020 for Cook County, Illinois, were used to identify parameters pertinent to the synthetic population. Twenty-seven experimental scenarios were examined to capture diverse strategies of THN distribution and use. Sensitivity analysis was performed to identify critical mediating and moderating variables associated with population impact and a proxy metric for cost-effectiveness (ie, the direct costs of THN kits distributed per death averted). Data were analyzed between February 2022 and March 2024. Intervention Modeled interventions included 3 THN distribution channels: community facilities and practitioners; jail, at release; and social network or peers of persons released from jail. Main Outcomes and Measures The primary outcome was the percentage of opioid-related overdose deaths averted with THN in the modeled population relative to a baseline scenario with no intervention. Results Take-home naloxone distribution at jail release had the highest median (IQR) percentage of averted deaths at 11.70% (6.57%-15.75%). The probability of bystander presence at an opioid overdose showed the greatest proportional contribution (27.15%) to the variance in deaths averted in persons released from jail. The estimated costs of distributed THN kits were less than $\$$15 000 per averted death in all 27 scenarios. Conclusions and Relevance This study found that THN distribution at jail release is an economical and feasible approach to substantially reducing opioid-related overdose mortality. Training and preparation of proficient and willing bystanders are central factors in reaching the full potential of this intervention.

Tatara, Eric [Argonne National Laboratory (ANL), A↗

Optimal Stopping Ages for Colorectal Cancer Screening

Importance Prior studies have shown that the benefits, harms, and costs of colorectal cancer (CRC) screening at older ages are associated with a patient’s sex, health, and screening history. However, these studies were hypothetical exercises and not directly informed by data on CRC risk. Objective To identify the optimal stopping ages for CRC screening by sex, comorbidity, and screening history from a cost-effectiveness perspective. Design, Setting, and Participants This economic evaluation first validated the MISCAN-Colon (Microsimulation Screening Analysis–Colon) model against community-based CRC incidence and mortality rates for 2 subcohorts of the PRECISE (Optimizing Colorectal Cancer Screening Precision and Outcomes in Community-Based Populations) cohort. Subsequently, different CRC screening scenarios were simulated in older individuals. Cohorts of US adults aged 76 to 90 years varied by sex and comorbidity status (none, low, moderate, or severe). Statistical and sensitivity analyses were performed from March 2023 to May 2024. Exposures CRC screening histories including fecal immunochemical test (FIT) or colonoscopy, such as a negative colonoscopy result from 10, 15, 20, 25, or 30 years before the index age; 1 to 5 negative FIT results within 5 years of the index age, with different patterns of recency; or a combination of negative colonoscopy and negative FIT results. Main Outcomes and Measures The main outcomes included estimated lifetime clinical outcomes, incremental costs, and quality-adjusted life-years gained (QALYG) associated with 1 additional FIT or colonoscopy. Optimal stopping age for screening, defined as the oldest age for which the incremental cost-effectiveness ratio was still below the willingness-to-pay threshold of $\$$100 000 per QALYG, was evaluated. Results The first of the 2 PRECISE subcohorts used in validating the simulation model included 25 974 adults (15 060 females [58.0%]; 54.7% aged 76 to 80 years) with a negative colonoscopy result 10 years before the index date. The second subcohort consisted of 118 269 adults (67 058 females [56.7%]; 90.5% aged 76 to 80 years) with a negative FIT result 1 year before the index date. Older age, male sex, higher comorbidity levels, and recent CRC screenings were associated with reduced incremental benefit and cost-effectiveness of additional screening. For the reference cohort of 76-year-old females without comorbidities and a negative colonoscopy result 10 years before the index age, 1 additional colonoscopy cost $\$$38 226 per QALYG. For cohorts with otherwise equivalent characteristics, associated costs increased to $\$$1 689 945 per QALYG for females at age 90 years without comorbidities and a negative colonoscopy results 10 years before the index age, $\$$51 604 per QALYG for males at age 76 years without comorbidities and a negative colonoscopy result 10 years before the index age, and $\$$108 480 per QALYG for females at age 76 years with severe comorbidities and a negative colonoscopy result 10 years before the index age and decreased to $\$$16 870 per QALYG for females without comorbidities and a negative colonoscopy result 30 years before the index age. The optimal stopping ages across different cohorts ranged from younger than 76 to 86 years for colonoscopy and younger than 76 to 88 years for FIT. Conclusions and Relevance In this economic evaluation, age, sex, screening history, comorbidity, and future screening modality were associated with the clinical outcomes, cost-effectiveness, and optimal stopping age for CRC screening. These results can inform guideline development and patient-directed informed decision-making.

Harlass, Matthias [Erasmus Erasmus University Medi↗

The Evolution of Randomized Clinical Trial Designs to Assess Therapeutics in Alzheimer Disease

Importance The success of recent randomized clinical trials (RCTs) for Alzheimer disease (AD), particularly those focusing on anti-amyloid therapies, has been discussed at length. However, the evolution of RCT design features for AD that preceded this success remain underexplored. Objective To describe temporal changes in the features of RCT design for interventions in AD. Evidence Review PubMed, Scopus, and Web of Science databases were searched in January 2025 for phase 2 and 3 AD RCTs published between January 1992 and December 2024. RCTs that investigated an intervention for AD, with a placebo or standard-of-care control group, were included. Four assessors independently reviewed full-text articles to capture study characteristics. Main Outcomes and Measures The number of participants and the duration of RCTs as well as the target population, outcomes, and funding were extracted from published reports. These features were analyzed with respect to time using linear regression and χ 2 analyses. Results The study included 203 RCTs with 79 589 participants testing interventions in AD. From 1992 to 2024, the mean sample size increased by 464% for phase 2 RCTs (from 42 to 237), and 50% for phase 3 RCTs (from 632 to 951), while the mean trial duration increased by 188% (from 16 to 46 weeks) for phase 2, and 256% (from 20 to 71 weeks) for phase 3 RCTs. This longer duration of RCTs may be partially attributed by a greater share of disease-modifying rather than symptomatic treatments. Similarly, more recent trials required AD biomarker evidence for enrollment (from 1 of 36 [2.7%] before 2006 to 40 of 76 [52.6%] since 2019). A substantial difference in the type of therapeutics researched was observed, with anti-amyloid and anti-tau RCTs being more likely to be funded by the pharmaceutical industry compared with neurotransmitter or other RCTs (anti-amyloid or anti-tau, 68 of 71 [95.8%]; neurotransmitter, 52 of 69 [77.6%]; other, 33 of 52 [63.5%]). RCT transparency improved, with more frequent data accessibility statements, registered reports, and better reporting on race and ethnicity. Conclusions and Relevance This methodology research of AD RCTs highlights substantial changes in key features of AD clinical trials from 1992 to 2024. AD RCTs have become larger and longer, such that they are powered to detect smaller clinical differences. The increased sample sizes and duration should enable the detection of smaller and more slowly occurring outcomes, which may lead to successful RCTs of therapies with slower and more subtle efficacy.

General & Internal Medicine↗