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Benefits of colorectal cancer screening using fecal immunochemical testing with varying positivity thresholds by age and sex

Background Fecal immunochemical test (FIT) performance for colorectal cancer screening varies by age and sex, yet most FIT-based screening programs use uniform positivity thresholds. This study assessed the potential benefits of stratifying FIT thresholds based on age and sex. Methods We conducted a meta-analysis of FIT sensitivity and specificity at various positivity thresholds by age and sex. We then used these estimates in 2 microsimulation models of colorectal cancer and projected lifetime clinical outcomes, incremental costs, and quality-adjusted life-years (QALYs) gained from age- and sex-stratified FIT strategies. FIT thresholds ranged from 10 to 50 µg hemoglobin per gram of feces. Results For current uniform FIT screening (20 µg hemoglobin/gram of feces), models projected 85.67 to 122.15 QALYs gained at incremental costs of ‒$982 to $504 per 1000 individuals compared with no screening. At equivalent costs to current uniform screening, only 1 model found stratified FIT approaches cost-effective, yielding a marginal increase of 1.04 and 1.10 QALYs gained/1000 female and male individuals, respectively. At a willingness-to-pay threshold of $100 000/QALYs gained, both models found stratified FIT cutoffs to be the best strategy, with cutoffs being equal to or higher for males and lowest at older ages (70-75 years). Uniform strategies showed comparable effectiveness, falling within 1 quality-adjusted life-day per person of efficient strategies at up to $112 more per person. Results were sensitive to FIT test performance characteristics and 1-time setup costs. Conclusion Stratifying FIT thresholds by age and sex may be cost-effective compared to current screening. The gain in expected health benefits with stratified FIT screening, however, is likely small.

Harlass, Matthias↗

ProZES: the methodology and software tool for assessment of assigned share of radiation in probability of cancer occurrence

ProZES is a software tool for estimating the probability that a given cancer was caused by preceding exposure to ionising radiation. ProZES calculates this probability, the assigned share, for solid cancers and hematopoietic malignant diseases, in cases of exposures to low-LET radiation, and for lung cancer in cases of exposure to radon. User-specified inputs include birth year, sex, type of diagnosed cancer, age at diagnosis, radiation exposure history and characteristics, and smoking behaviour for lung cancer. Cancer risk models are an essential part of ProZES. Linking disease and exposure to radiation involves several methodological aspects, and assessment of uncertainties received particular attention. ProZES systematically uses the principle of multi-model inference. Models of radiation risk were either newly developed or critically re-evaluated for ProZES, including dedicated models for frequent types of cancer and, for less common diseases, models for groups of functionally similar cancer sites. The low-LET models originate mostly from the study of atomic bomb survivors in Hiroshima and Nagasaki. Risks predicted by these models are adjusted to be applicable to the population of Germany and to different time periods. Adjustment factors for low dose rates and for a reduced risk during the minimum latency time between exposure and cancer are also applied. The development of the methodology and software was initiated and supported by the German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU) taking up advice by the German Commission on Radiological Protection (SSK, Strahlenschutzkommission). These provide the scientific basis to support decision making on compensation claims regarding malignancies following occupational exposure to radiation in Germany.

97 MATHEMATICS AND COMPUTING↗

Development and validation of a 30-day mortality index based on pre-existing medical administrative data from 13,323 COVID-19 patients: The Veterans Health Administration COVID-19 (VACO) Index

Background Available COVID-19 mortality indices are limited to acute inpatient data. Using nationwide medical administrative data available prior to SARS-CoV-2 infection from the US Veterans Health Administration (VA), we developed the VA COVID-19 (VACO) 30-day mortality index and validated the index in two independent, prospective samples. Methods and findings We reviewed SARS-CoV-2 testing results within the VA between February 8 and August 18, 2020. The sample was split into a development cohort (test positive between March 2 and April 15, 2020), an early validation cohort (test positive between April 16 and May 18, 2020), and a late validation cohort (test positive between May 19 and July 19, 2020). Our logistic regression model in the development cohort considered demographics (age, sex, race/ethnicity), and pre-existing medical conditions and the Charlson Comorbidity Index (CCI) derived from ICD-10 diagnosis codes. Weights were fixed to create the VACO Index that was then validated by comparing area under receiver operating characteristic curves (AUC) in the early and late validation cohorts and among important validation cohort subgroups defined by sex, race/ethnicity, and geographic region. We also evaluated calibration curves and the range of predictions generated within age categories. 13,323 individuals tested positive for SARS-CoV-2 (median age: 63 years; 91% male; 42% non-Hispanic Black). We observed 480/3,681 (13%) deaths in development, 253/2,151 (12%) deaths in the early validation cohort, and 403/7,491 (5%) deaths in the late validation cohort. Age, multimorbidity described with CCI, and a history of myocardial infarction or peripheral vascular disease were independently associated with mortality–no other individual comorbid diagnosis provided additional information. The VACO Index discriminated mortality in development (AUC = 0.79, 95% CI: 0.77–0.81), and in early (AUC = 0.81 95% CI: 0.78–0.83) and late (AUC = 0.84, 95% CI: 0.78–0.86) validation. The VACO Index allows personalized estimates of 30-day mortality after COVID-19 infection. For example, among those aged 60–64 years, overall mortality was estimated at 9% (95% CI: 6–11%). The Index further discriminated risk in this age stratum from 4% (95% CI: 3–7%) to 21% (95% CI: 12–31%), depending on sex and comorbid disease. Conclusion Prior to infection, demographics and comorbid conditions can discriminate COVID-19 mortality risk overall and within age strata. The VACO Index reproducibly identified individuals at substantial risk of COVID-19 mortality who might consider continuing social distancing, despite relaxed state and local guidelines.

60 APPLIED LIFE SCIENCES↗

Making it in academic psychology: Demographic and personality correlates of eminence

Citations to published work, personality, and demographic characteristics were examined in a sample of male and female academic psychologists. A large sex difference was found in citations with men receiving significantly more recognition. Reputational rankings of graduate school and current institution were significantly related to citations, as were components of achievement motivation. Mastery and work needs were positively related to citations while competitiveness was negatively associated with the criterion. A model of attainment in psychology is proposed and possible explanations for the differential recognition of women are explored.

Helmreich, R. L.↗

Tau Positron Emission Tomography for Predicting Dementia in Individuals With Mild Cognitive Impairment

An accurate prognosis is especially pertinent in mild cognitive impairment (MCI), when individuals experience considerable uncertainty about future progression. To evaluate the prognostic value of tau positron emission tomography (PET) to predict clinical progression from MCI to dementia. This was a multicenter cohort study with external validation and a mean (SD) follow-up of 2.0 (1.1) years. Data were collected from centers in South Korea, Sweden, the US, and Switzerland from June 2014 to January 2024. Participant data were retrospectively collected and inclusion criteria were a baseline clinical diagnosis of MCI; longitudinal clinical follow-up; a Mini-Mental State Examination (MMSE) score greater than 22; and available tau PET, amyloid-β (Aβ) PET, and magnetic resonance imaging (MRI) scan less than 1 year from diagnosis. A total of 448 eligible individuals with MCI were included (331 in the discovery cohort and 117 in the validation cohort). None of these participants were excluded over the course of the study. Exposures included Tau PET, Aβ PET, and MRI. Positive results on tau PET (temporal meta–region of interest), Aβ PET (global; expressed in the standardized metric Centiloids), and MRI (Alzheimer disease [AD] signature region) was assessed using quantitative thresholds and visual reads. Clinical progression from MCI to all-cause dementia (regardless of suspected etiology) or to AD dementia (AD as suspected etiology) served as the primary outcomes. The primary analyses were receiver operating characteristics. In the discovery cohort, the mean (SD) age was 70.9 (8.5) years, 191 (58%) were male, the mean (SD) MMSE score was 27.1 (1.9), and 110 individuals with MCI (33%) converted to dementia (71 to AD dementia). Only the model with tau PET predicted all-cause dementia (area under the receiver operating characteristic curve [AUC], 0.75; 95% CI, 0.70-0.80) better than a base model including age, sex, education, and MMSE score (AUC, 0.71; 95% CI, 0.65-0.77; P = .02), while the models assessing the other neuroimaging markers did not improve prediction. In the validation cohort, tau PET replicated in predicting all-cause dementia. Compared to the base model (AUC, 0.75; 95% CI, 0.69-0.82), prediction of AD dementia in the discovery cohort was significantly improved by including tau PET (AUC, 0.84; 95% CI, 0.79-0.89; P < .001), tau PET visual read (AUC, 0.83; 95% CI, 0.78-0.88; P = .001), and Aβ PET Centiloids (AUC, 0.83; 95% CI, 0.78-0.88; P = .03). In the validation cohort, only the tau PET and the tau PET visual reads replicated in predicting AD dementia. In this study, tau-PET showed the best performance as a stand-alone marker to predict progression to dementia among individuals with MCI. This suggests that, for prognostic purposes in MCI, a tau PET scan may be the best currently available neuroimaging marker.

59 BASIC BIOLOGICAL SCIENCES↗

Assessing the Risk of Crew Injury Due to Dynamic Loads During Spaceflight

Spaceflight requires tremendous amounts of energy to achieve Earth orbit and to attain escape velocity for interplanetary missions. Although the majority of the energy is managed in such a way as to limit the accelerations on the crew, several mission phases may result in crew exposure to dynamic loads. In the automotive industry, risk of serious injury can be tolerated because the probability of a crash is remote each time a person enters a vehicle, resulting in a low total risk of injury. For spaceflight, the level of acceptable injury risk must be lower to achieve a low total risk of injury because the dynamic loads are expected on each flight. To mitigate the risk of injury due to dynamic loads, the NASA Human Research Program has developed a research plan to inform the knowledge gaps and develop relevant tools for assessing injury risk. The risk of injury due to dynamic loads can be further subdivided into extrinsic and intrinsic risk factors. Extrinsic risk factors include the vehicle dynamic profile, seat and restraint design, and spacesuit design. Human tolerance to loads varies considerably depending on the direction, amplitude, and rise-time of acceleration therefore the orientation of the body to the dynamic vector is critical to determining crew risk of injury. Although a particular vehicle dynamic profile may be safe for a particular design, the seat, restraint, and suit designs can affect the risk of injury due to localized effects. In addition, characteristics intrinsic to the crewmember may also contribute to the risk of injury, such as crewmember sex, age, anthropometry, and deconditioning due to spaceflight, and each astronaut may have a different risk profile because of these factors. The purpose of the research plan is to address any knowledge gaps in the risk factors to mitigate injury risk. Methods for assessing injury risk have been well documented in other analogous industries and include human volunteer testing, human exposure to dynamic environments, post-mortem human subject (PMHS) testing, animal testing, anthropomorphic test devices (ATD), dynamic models of the human, numerical models of ATDs, and numerical models of the human. Each has inherent strengths and limitations. For example, human volunteer testing is advantageous because a population can be selected that is similar to the astronaut corps; however, because of the inherent ethical limitations, only sub-injurious conditions can be tested. PMHSs can be tested in a variety of conditions including injurious levels, but the responses are not completely analogous to living human subjects. In addition, it is exceedingly difficult to select a PMHS population that is similar to the astronaut corps. ATDs are currently widely used in the automotive industry and military because they are highly repeatable and durable. Unfortunately, because they are mechanical models of the human body, the biofidelity of the responses are limited to dynamic conditions used to validate the ATD. Numerical models of the ATD, in addition to the strengths and limitations for ATDs, are easy to use for a variety of designs before a design is fabricated, but also have additional limitations for ATDs, are easy to use for a variety of designs before a design is fabricated, but also have additional uncertainty. Dynamic models are simple and easy to use, but do not account for localized effects of the seat and suit. Finally, numerical models of the human have the potential to have the most advantages; however, the current models are not validated for the conditions expected during spaceflight. To properly assess spaceflight conditions with numerical human models, human data would be needed to optimize the model responses for those conditions. Using the appropriate assessment method with the knowledge gained for each risk factor, an appropriate approach for mitigating the risk of injury due to dynamic loads can be developed ensuring crew safety in future NASA vehicles.

Somers, J. T.↗

Brain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium

Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18–72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18–73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on 68 measures of cortical thickness and surface area, 7 subcortical volumes, lateral ventricular volumes and total intracranial volume, all derived from T1-weighted brain magnetic resonance imaging (MRI) scans. Deviations from a healthy brain ageing trajectory were assessed by the difference between brain-predicted age and chronological age (brain-predicted age difference [brain-PAD]). On average, SZ patients showed a higher brain-PAD of +3.55 years (95% CI: 2.91, 4.19; I 2 = 57.53%) compared to controls, after adjusting for age, sex and site (Cohen’s d = 0.48). Among SZ patients, brain-PAD was not associated with specific clinical characteristics (age of onset, duration of illness, symptom severity, or antipsychotic use and dose). This large-scale collaborative study suggests advanced structural brain ageing in SZ. Longitudinal studies of SZ and a range of mental and somatic health outcomes will help to further evaluate the clinical implications of increased brain-PAD and its ability to be influenced by interventions.

59 BASIC BIOLOGICAL SCIENCES↗

Spatial and temporal variation in nest temperatures forecasts sex ratio skews in a crocodilian with environmental sex determination

Species displaying temperature-dependent sex determination (TSD) are especially vulnerable to the effects of a rapidly changing global climate due to their profound sensitivity to thermal cues during development. Predicting the consequences of climate change for these species, including skewed offspring sex ratios, depends on understanding how climatic factors interface with features of maternal nesting behaviour to shape the developmental environment. Here, we measure thermal profiles in 86 nests at two geographically distinct sites in the northern and southern regions of the American alligator's ( Alligator mississippiensis ) geographical range, and examine the influence of both climatic factors and maternally driven nest characteristics on nest temperature variation. Changes in daily maximum air temperatures drive annual trends in nest temperatures, while variation in individual nest temperatures is also related to local habitat factors and microclimate characteristics. Without any compensatory nesting behaviours, nest temperatures are projected to increase by 1.6–3.7°C by the year 2100, and these changes are predicted to have dramatic consequences for offspring sex ratios. Exact sex ratio outcomes vary widely depending on site and emission scenario as a function of the unique temperature-by-sex reaction norm exhibited by all crocodilians. By revealing the ecological drivers of nest temperature variation in the American alligator, this study provides important insights into the potential consequences of climate change for crocodilian species, many of which are already threatened by extinction.

Environmental Sciences & Ecology↗

Behavioral state resource selection in invasive wild pigs in the Southeastern United States

Elucidating correlations between wild pig ( Sus scrofa ) behavior and landscape attributes can aid in the advancement of management strategies for controlling populations. Using GPS data from 49 wild pigs in the southeastern U.S., we used hidden Markov models to define movement path characteristics and assign behaviors (e.g., resting, foraging, travelling). We then explored the connection between these behaviors and resource selection for both sexes between two distinct seasons based on forage availability (i.e., low forage, high forage). Females demonstrated a crepuscular activity pattern in the high-forage season and a variable pattern in the low-forage season, while males exhibited nocturnal activity patterns across both seasons. Wild pigs selected for bottomland hardwoods and dense canopy cover in all behavioral states in both seasons. Males selected for diversity in vegetation types while foraging in the low-forage season compared to the high-forage season and demonstrated an increased use of linear anthropogenic features across seasons while traveling. Wild pigs can establish populations and home ranges in an array of landscapes, but our results demonstrate male and female pigs exhibit clear differences in movement behavior and there are key resources associated with common behaviors that can be targeted to improve the efficiency of management programs.

54 ENVIRONMENTAL SCIENCES↗

Cancer survival in the United States 2007–2016: Results from the National Program of Cancer Registries

Background Cancer survival has improved for the most common cancers. However, less improvement and lower survival has been observed in some groups perhaps due to differential access to cancer care including prevention, screening, diagnosis, and treatment. Methods To further understand contemporary relative cancer survival (one- and five- year), we used survival data from CDC’s National Program of Cancer Registries (NPCR) for cancers diagnosed during 2007–2016. We examined overall relative cancer survival by sex, race and ethnicity, age, and county-level metropolitan and non-metropolitan status. Relative cancer survival by metropolitan and non-metropolitan status was further examined by sex, race and ethnicity, age, and cancer type. Results Among persons with cancer diagnosed during 2007–2016 the overall one-year and five-year relative survival was 80.6% and 67.4%, respectively. One-year relative survival for persons living in metropolitan counties was 81.1% and 77.8% among persons living in non-metropolitan counties. We found that persons who lived in non-metropolitan counties had lower survival than those who lived in metropolitan counties, and this difference persisted across sex, race and ethnicity, age, and most cancer types. Conclusion Further examination of the differences in cancer survival by cancer type or other characteristics might be helpful for identifying potential interventions, such as programs that target screening and early detection or strategies to improve access to high quality cancer treatment and follow-up care, that could improve long-term outcomes. Impact This analysis provided a high-level overview of contemporary cancer survival in the United States.

60 APPLIED LIFE SCIENCES↗

Steelhead ( Oncorhynchus mykiss ) lineages and sexes show variable patterns of association of adult migration timing and age‐at‐maturity traits with two genomic regions

Abstract As life history diversity plays a critical role in supporting the resilience of exploited populations, understanding the genetic basis of those life history variations is important for conservation management. However, effective application requires a robust understanding of the strength and universality of genetic associations. Here, we examine genetic variation of single nucleotide polymorphisms in genomic regions previously associated with migration phenology and age‐at‐maturity in steelhead ( Oncorhynchus mykiss ) from the Columbia River. We found chromosome 28 markers (GREB1L, ROCK1 genes) explained significant variance in migration timing in both coastal and inland steelhead. However, strength of association was much greater in coastal than inland steelhead ( R 2 0.51 vs. 0.08), suggesting that genomic background and challenging inland migration pathways may act to moderate effects of this region. Further, we found that chromosome 25 candidate markers (SIX6 gene) were significantly associated with age and size at first return migration for inland steelhead, and this pattern was mediated by sex in a predictable pattern (males R 2 = 0.139–0.170; females R 2 = 0.096–0.111). While this encourages using these candidate regions in predicting life history characteristics, we suggest that stock‐specific associations and haplotype frequencies will be useful in guiding implementation of genetic assays to inform management.

Willis, Stuart C.↗

Comet P/Halley 1910, 1986: An objective-prism study

V. M. Slipher of the Lowell Obs. collected a large amount of spectroscopic data during the 1910 apparition of Halley's comet. Three of his post perihelion objective-prism plates were selected, digitized, and subjected to modern digital data reduction procedures. Some of the important steps in the analysis where: (1) Density to intensity conversion for which was used 1910 slit spectra of Fe-arc lamp on similar plates (Sigma) and derived an average characteristic curve; (2) Flux calibration using the fact that during the period June 2 to 7 1910 P/Halley was very close (angular distance) to the bright star Alpha Sex (A0III, V-4.49), and the spectra of both star and comet were recorded on the same plates. The flux distribution of Alpha Sex was assumed to be similar to that of the standard star 58 Aql and derived a sensitivity curve for the system; (3) Atmospheric extinction using the standard curve for the Lowell Obs.; (4) Solar continuum subtraction using the standard solar spectrum binned to the spectral resolution. An example of a flux-calibrated spectrum of the coma (integrated over 87,000km) before the subtraction of solar continuum is presented.

Carsenty, U.↗

Engineering, Life Sciences, and Health/Medicine Synergy in Aerospace Human Systems Integration: The Rosetta Stone Project

In the realm of aerospace engineering and the physical sciences, we have developed laws of physics based on empirical and research evidence that reliably guide design, research, and development efforts. For instance, an engineer designs a system based on data and experience that can be consistently and repeatedly verified. This reproducibility depends on the consistency and dependability of the materials on which the engineer works and is subject to physics, geometry and convention. In life sciences and medicine, these apply as well, but individuality introduces a host of variables into the mix, resulting in characteristics and outcomes that can be quite broad within a population of individuals. This individuality ranges from differences at the genetic and cellular level to differences in an individuals personality and abilities due to sex and gender, environment, education, etc.

Medicine↗

Cross‐Cultural Validation of the Binge Eating Disorder Screener‐7 ( BEDS ‐7) Across 42 Countries

ABSTRACT Objective This study aimed to evaluate the reliability and validity of the Binge Eating Disorder Screener‐7 (BEDS‐7) across 42 countries and 26 languages, assessing its reliability and validity as a screening tool for binge‐eating disorder (BED) in diverse cultural contexts. Specifically, it sought to enhance early recognition of BED symptoms in primary care settings globally, contributing to a standardized framework for assessing BED. Method The International Sex Survey, a cross‐sectional online study, was conducted in 42 countries and 26 languages. A diverse community sample of 82,243 participants, aged 18 years or older, completed the BEDS‐7 and measures of sexuality, mental health, substance use, and sociodemographic characteristics. Confirmatory factor analyses and tests of measurement invariance were employed to evaluate the reliability and validity of the BEDS‐7 across languages, countries, genders, and sexual orientations. Results The BEDS‐7 demonstrated scalar factorial invariance across languages and countries, indicating consistent factor loadings and item intercepts. In contrast, the screener showed residual invariance across gender and sexual orientation groups, supporting its robustness across these demographics. Kruskal–Wallis tests revealed significant differences in BED symptoms across languages, countries, genders, and sexual orientations, with the highest BED scores observed among queer, pansexual, and gender‐diverse individuals. The BEDS‐7 also demonstrated adequate reliability (Cronbach's alpha > 0.80) and moderate criterion validity. Discussion The findings provide further evidence of the reliability and validity of the BEDS‐7 as a potential screening tool for identifying probable cases of BED globally, facilitating early intervention in primary care settings.

Gewirtz‐Meydan, Ateret [School of Social Work, Fac↗

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↗

Characterizing Fractures Across the Astronaut Corps: Preliminary Findings from Population-Level Analysis

Despite evidence of bone loss during spaceflight and operational countermeasures to mitigate this loss, the subsequent risk of fracture among astronauts is not known. The physiologic process of diminished bone density and bone recovery during or following spaceflight is multifactorial. Such factors as age, sex, fracture history, and others may combine to increase fracture risk among astronauts. As part of the 2016 Bone Research and Clinical Advisory Panel (RCAP), the authors analyzed data collected on 338 NASA astronauts to describe the demographics, bone-relevant characteristics, and fracture history of the astronaut population. The majority of the population are male (n=286, 84.6%), have flown at least one mission (n=306, 90.5%), and were between the ages of 30 and 49 at first mission (n=296, 96.7% of those with at least one mission). Of the 338 astronauts, 241 (71.3%) experienced a fracture over the course of their lifetime. One hundred and five (43.5%) of these 241 astronauts only experienced a fracture prior to being selected into the Astronaut Corps, whereas 53 (22.0%) only experienced a fracture after selection as an astronaut. An additional 80 astronauts (33.2%) had both pre- and post-selection fractures. The remaining 3 astronauts had a fracture of unknown date, which could not be categorized as pre- or post-selection. Among the 133 astronauts with at least one post-selection fracture, males comprised 90.2% (n=120) compared to 84.5% of the entire Corps, and females accounted for 9.8% (n=13) compared to 15.4% of the Corps. Ninety-seven of the 133 astronauts with post-selection fractures (72.9%) had one fracture event, 22 (16.5%) had two fractures, and 14 (10.5%) had three or more fractures. Some astronauts with multiple fractures suffered these in a single event, such as an automobile accident. The 133 astronauts with a post-selection fracture accounted for a total of 188 fracture events. One hundred and four (78.2%) of astronauts with post-selection fractures experienced those fractures following their first mission (mean 12.7 +/- 11.1 years following first mission; range 14.0 days - 50.6 years). Additional analyses are ongoing and include examination of fracture history, skeletal site, mechanism, and type of fracture, age at time of fracture, time from spaceflight to fracture, as well as multivariable analysis comparing fracture events to non-events. The results of such analyses may reveal trends in risk factors for fracture among the astronaut corps that have yet to be systematically described through a corps-wide approach.

Rossi, Meredith M.↗

A Chromosome-Scale Genome Assembly of a Helicoverpa zea Strain Resistant to Bacillus thuringiensis Cry1Ac Insecticidal Protein

Helicoverpa zea (Lepidoptera: Noctuidae) is an insect pest of major cultivated crops in North and South America. The species has adapted to different host plants and developed resistance to several insecticidal agents, including Bacillus thuringiensis (Bt) insecticidal proteins in transgenic cotton and maize. Helicoverpa zea populations persist year-round in tropical and subtropical regions, but seasonal migrations into temperate zones increase the geographic range of associated crop damage. To better understand the genetic basis of these physiological and ecological characteristics, we generated a high-quality chromosome-level assembly for a single H. zea male from Bt-resistant strain, HzStark_Cry1AcR. Hi-C data were used to scaffold an initial 375.2 Mb contig assembly into 30 autosomes and the Z sex chromosome (scaffold N50 = 12.8 Mb and L50 = 14). The scaffolded assembly was error-corrected with a novel pipeline, polishCLR. The mitochondrial genome was assembled through an improved pipeline and annotated. Assessment of this genome assembly indicated 98.8% of the Lepidopteran Benchmark Universal Single-Copy Ortholog set were complete (98.5% as complete single copy). Repetitive elements comprised approximately 29.5% of the assembly with the plurality (11.2%) classified as retroelements. This chromosome-scale reference assembly for H. zea, ilHelZeax1.1, will facilitate future research to evaluate and enhance sustainable crop production practices.

59 BASIC BIOLOGICAL SCIENCES↗

Comparison of hormone and electrolyte circadian rhythms in male and female humans

Circadian rhythm characteristics in healthy male and female humans were studied at 4-hour intervals for urine volume, cortisol, 5-hydroxyindoleacetic acid (5-HIAA), Na, K, Na/K ratios in the urine, as well as plasma cortisol. While plasma and urinary cortisol rhythms were very similar in both sexes, the described rhythms in urine volume, electrolyte, and 5-HIAA excretion differ for the two sexes. The results suggest that sex differences exist in the circadian patterns of important hormone and metabolic functions and that the internal synchrony of circadian rhythms differs for the two sexes. The results seem to indicate that the rhythmical secretion of cortisol does not account for the pattern of Na and K excretion.

Vernikos-Danellis, J.↗