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All sourcesNASA NTRSDOE OSTI
NASA NTRS1996

Effect of Altered Gravity Environment on Tobacco Hornworm (Manduca Sexta) Development

Metamorphosis provides a unique condition for studying the role of gravity in development. Formation of new organs in a previously existing organism requires a highly active period of turnover of amino acids and proteins, and of changes in the endocrine profile. Furthermore, metamorphosis offers the advantage of studying a self-contained biological system. The tobacco hornworm provides a suitable species to study the effect of altered gravitational environment on invertebrate development. This species has been one of the most thoroughly investigated organisms in a variety of aspects of insect biology. M. sexta pharate adults can provide significant amounts of material with which to work, thus facilitating the study of metabolic aspects of adult development. During wandering, the period immediately following cessation of larval feeding, the larva burrows into the soil to form a pupation chamber. Despite burrowing down 25 to 30 cm, the insects reorient themselves to a slightly head-up (10 +/- 1 degree) position. Since light and temperature are not factors in this process, the larvae must sense the gravity vector. In our ground-based studies we had assessed whether developing adults might be sensitive to their gravitational environment by orienting pupae in a vertical head-up position within 24 to 48 h after pupal ecdysis. Our ground-based findings formed the foundation for determining which parameters would be evaluated in developing Manduca following spaceflight. Measurements were to include: (1) extent of development by all of the insects, (2) analysis of hemolymph obtained from half of the insects postflight for ecdysteroid, amino acid, urea, ammonia and trehalose concentrations, (3) further development of the other half of the insects to adult (moths), (4) analysis of the flight muscle protein content of the adults. Based on the first flight attempt in July, 1995, we modified the BRIC hardware to accommodate the insects. Our studies after BRIC-04 showed that sealing the top and bottom lids of the canisters with an 0-ring and with vacuum grease caused the insects to stop developing because of accumulation of carbon dioxide. Even though removing both the O-rings and vacuum grease permitted normal development, there was still some increase in carbon dioxide levels. Consequently, the canisters were vented and the vents covered with gas permeable membrane.

Tischler, Marc E.↗
NASA NTRS1999

Laser ablation of persistent twist cells in Drosophila: muscle precursor fate is not segmentally restricted

In Drosophila the precursors of the adult musculature arise during embryogenesis. These precursor cells have been termed Persistent Twist Cells (PTCs), as they continue to express the transcription factor Twist after that gene ceases expression elsewhere in the mesoderm. In the larval abdomen, the PTCs are associated with peripheral nerves in stereotypic ventral, dorsal, and lateral clusters, which give rise, respectively, to the ventral, dorsal, and lateral muscle fiber groups of the adult. We tested the developmental potential of the PTCs by using a microbeam laser to ablate specific clusters in larvae. We found that the ablation of a single segmental PTC cluster does not usually result in the deletion of the corresponding adult fibers of that segment. Instead, normal or near normal numbers of adult fibers can form after the ablation. Examination of pupae following ablation showed that migrating PTCs from adjacent segments are able to invade the affected segment, replenishing the ablated cells. However, the ablation of homologous PTCs in multiple segments does result in the deletion of the corresponding adult muscle fibers. These data indicate that the PTCs in an abdominal segment can contribute to the formation of muscle fibers in adjacent abdominal segments, and thus are not inherently restricted to the formation of muscle fibers within their segment of origin.

NASA Discipline Neuroscience↗
NASA NTRS2005

Prenatal Centrifugation: A Mode1 for Fetal Programming of Body Weight?

'Fetal programming' is a newly emerging field that is revealing astounding insights into the prenatal origins of adult disease, including metabolic, endocrine, and cardiovascular pathophysiology. In the present study, we tested the hypothesis that rat pups conceived, gestated and born at 2-g have significantly reduced birth weights and increased adult body weights as compared to 1-g controls. Offspring were produced by mating young adult male and female rats that were adapted to 2-g centrifugation. Female rats underwent conception, pregnancy and birth at 2-g. Newborn pups in the 2-g condition were removed from the centrifuge and fostered to non-manipulated, newly parturient dams maintained at 1 -g. Comparisons were made with 1-g stationary controls, also crossfostered at birth. As compared to 1-g controls, birth weights of pups gestated and born at 2-g were significantly reduced. Pup body weights were significantly reduced until Postnatal day (P) 12. Beginning on P63, body weights of 2-g-gestated offspring exceeded those of 1-g controls by 7-10%. Thus, prenatal rearing at 2-g restricts neonatal growth and increases adult body weight. Collectively, these data support the hypothesis that 2-g centrifugation alters the intrauterine milieu, thereby inducing persistent changes in adult phenotype.

Baer, Lisa A.↗
DOE OSTI2025

Assessment of diagenesis in archaeological human second metacarpal bones using the intensity of the small angle X-ray scattering D -period peak

Bone consists mainly of carbonated apatite (cAp) nanoplatelets embedded in a matrix of collagen fibrils. Earlier, high-energy small angle X-ray scattering (SAXS) studies of archaeological adult human second metacarpal bones (mc2) found collagen D-period peaks with high-intensity I D in specimens in which microcomputed tomography (microCT) showed little diagenesis and I D ~ 0 for specimens where microCT revealed severe diagenesis (Park et al. 2022 Int. J. Osteoarchaeol. 32, 170–181 (doi:10.1002/oa.3053); Stock et al. 2022 Int. J. Osteoarchaeol. 32, 120–131 (doi:10.1002/oa.3049)). Here, the present paper uses SAXS at beamline 1-ID, Advanced Photon Source, Argonne National Laboratory and other techniques to study a set of 10 mc2 from an early Medieval cemetery at Greding, Germany. We hypothesized that non-invasive measurement of I D would provide an accurate and rapid (approx. 6 min/specimen) assessment of diagenesis in archaeological mc2. Results of Raman spectroscopy, laboratory microCT and backscattered electron, reflected light and polarized transmitted light microscopies confirmed the SAXS determinations, but lattice parameter values from X-ray diffraction were uncorrelated with I D value. Age-at-death estimates placed the 10 mc2 in three age categories (young adult, middle adult, old adult): lattice parameters from X-ray diffraction were uncorrelated with age at death. Cross-sectional bone area fraction from microCT dropped noticeably for the older age cohort.

Raman spectroscopy↗
DOE OSTI2025

Exploiting Trap Type and Color for Monitoring Macadamia Felted Coccid Acanthococcus ironsidei (Williams) and Associated Parasitic Wasps in Macadamia Orchards in Hawai’i

Acanthococcus ironsidei (Williams) (Hemiptera: Eriococcidae) is an invasive pest of macadamia, Macadamia integrifolia, in Hawai’i, causing death to macadamia trees and decreased nut productivity. Monitoring relies on wrapping double-sided sticky tapes over tree branches to trap dispersing crawlers (i.e., mobile immature stage), but this is tedious for growers, especially in large orchards. From September to November 2022 and December 2022 to February 2023, at two commercial macadamia orchards on Hawai’i Island, the use of colored sticky cards was assessed for improving the monitoring of A. ironsidei and to investigate the Hymenopteran parasitoid complex that inhabits macadamia canopies. At each study site, four different colored sticky cards (yellow, lime green, dark green, and white) were placed on the lower canopy of five trees, and on each tree, a transparent double-sided sticky tape was deployed. At bi-weekly intervals, the sticky cards were replaced and re-randomized on each tree, and the double-sided sticky tapes were replaced. The results showed that the sticky cards captured both A. ironsidei crawlers and (winged) male adults, while the double-sided sticky tapes captured only crawlers. The trap color did not have significant effects on the captures of A. ironsidei male adults at the sites, while the captures of crawlers on sticky cards were lowest on the dark green sticky traps at one site. The captures of A. ironsidei adult males on white sticky traps were generally correlated with the number of crawlers captured on the double-sided sticky tapes. The parasitoid complex captured had disparities in the attraction to color; however, the yellow, lime green and dark green colors were seemingly more effective for monitoring Encarsia lounsburyi (Berlese & Paoli), a reported parasitoid of A. ironsidei. These results have useful practical implications for improved monitoring of A. ironsidei crawlers, male adults and associated natural enemies.

Entomology↗
NASA NTRS1974

Bone mineral content in normal US whites

Photon absorptiometry with I-125 was used to measure the bone mineral content and the bone width on 763 children between the ages of 5 and 19 years, on 538 adults between the ages of 20 and 49 years, and on 550 adults over the age of 50 years. Measurements were made on the midshaft and the distal end of the radius and the ulna, and on the humerus midshaft. This has permitted analysis of annual bone growth in children, and the rate of change in elderly adults per decade. Male and female children grew at about the same rate until adolescence. After adolescence females grew at a slow rate until the mid-twenties, while males reached adult mineralization by age 20. Males remained relatively constant until the fifties, and females began their decline in the forties.

Mazess, R. B.↗
NASA NTRS2002

Decreases in bone blood flow and bone material properties in aging Fischer-344 rats

The purpose of this study was to quantify precisely aging-induced changes in skeletal perfusion and bone mechanical properties in a small rodent model. Blood flow was measured in conscious juvenile (2 months old), adult (6 months old), and aged (24 months old) male Fischer-344 rats using radiolabeled microspheres. There were no significant differences in bone perfusion rate or vascular resistance between juvenile and adult rats. However, blood flow was lower in aged versus adult rats in the forelimb bones, scapulas, and femurs. To test for functional effects of this decline in blood flow, bone mineral density and mechanical properties were measured in rats from these two age groups. Bone mineral density and cross-sectional moment of inertia in femoral and tibial shafts and the femoral neck were significantly larger in the aged versus adult rats, resulting in increased (+14%-53%) breaking strength and stiffness. However, intrinsic material properties at midshaft of the long bones were 12% to 25% lower in the aged rats. Although these data are consistent with a potential link between decreased perfusion and focal alterations in bone remodeling activity related to clinically relevant bone loss, additional studies are required to establish the mechanisms for this putative relationship.

Non-NASA Center↗
NASA NTRS2001

Developmental regulation of N-methyl-D-aspartate- and kainate-type glutamate receptor expression in the rat spinal cord

Spinal motor neurons undergo experience-dependent development during a critical period in early postnatal life. It has been suggested that the repertoire of glutamate receptor subunits differs between young and mature motor neurons and contributes to this activity-dependent development. In the present study we examined the expression patterns of N-methyl-D-aspartate- and kainate-type glutamate receptor subunits during the postnatal maturation of the spinal cord. Young motor neurons express much higher levels of the N-methyl-D-aspartate receptor subunit NR1 than do adult motor neurons. Although there are eight potential splice variants of NR1, only a subgroup is expressed by motor neurons. With respect to NR2 receptor subunits, young motor neurons express NR2A and C, while adult motor neurons express only NR2A. Young motor neurons express kainate receptor subunits GluR5, 6 and KA2 but we are unable to detect these or any other kainate receptor subunits in the adult spinal cord. Other spinal cord regions display a distinct pattern of developmental regulation of N-methyl-D-aspartate and kainate receptor subunit expression in comparison to motor neurons. Our findings indicate a precise spatio-temporal regulation of individual subunit expression in the developing spinal cord. Specific combinations of subunits in developing neurons influence their excitable properties and could participate in the emergence of adult neuronal form and function.

NASA Discipline Cell Biology↗
NASA NTRS2000

The A/P axis in echinoderm ontogeny and evolution: evidence from fossils and molecules

Even though echinoderms are members of the Bilateria, the location of their anterior/posterior axis has remained enigmatic. Here we propose a novel solution to the problem employing three lines of evidence: the expression of a posterior class Hox gene in the coeloms of the nascent adult body plan within the larva; the anatomy of certain early fossil echinoderms; and finally the relation between endoskeletal plate morphology and the associated coelomic tissues. All three lines of evidence converge on the same answer, namely that the location of the adult mouth is anterior, and the anterior/posterior axis runs from the mouth through the adult coelomic compartments. This axis then orients the animal such that there is but a single plane of symmetry dividing the animal into left and right halves. We tentatively hypothesize that this plane of symmetry is positioned along the dorsal/ventral axis. These axis identifications lead to the conclusion that the five ambulacra are not primary body axes, but instead are outgrowths from the central anterior/posterior axis. These identifications also shed insight into several other evolutionary mysteries of various echinoderm clades such as the independent evolution of bilateral symmetry in irregular echinoids, but do not elucidate the underlying mechanisms of the adult coelomic architecture.

Non-NASA Center↗
NASA NTRS2000

Quantitative assessment of Hox complex expression in the indirect development of the polychaete annelid Chaetopterus sp

A prediction from the set-aside theory of bilaterian origins is that pattern formation processes such as those controlled by the Hox cluster genes are required specifically for adult body plan formation. This prediction can be tested in animals that use maximal indirect development, in which the embryonic formation of the larva and the postembryonic formation of the adult body plan are temporally and spatially distinct. To this end, we quantitatively measured the amount of transcripts for five Hox genes in embryos of a lophotrochozoan, the polychaete annelid Chaetopterus sp. The polychaete Hox complex is shown not to be expressed during embryogenesis, but transcripts of all measured Hox complex genes are detected at significant levels during the initial stages of adult body plan formation. Temporal colinearity in the sequence of their activation is observed, so that activation follows the 3'-5' arrangement of the genes. Moreover, Hox gene expression is spatially localized to the region of teloblastic set-aside cells of the later-stage embryos. This study shows that an indirectly developing lophotrochozoan shares with an indirectly developing deuterostome, the sea urchin, a common mode of Hox complex utilization: construction of the larva, whether a trochophore or dipleurula, does not involve Hox cluster expression, but in both forms the complex is expressed in the set-aside cells from which the adult body plan derives.

Non-NASA Center↗
NASA NTRS1999

Time course of myosin heavy chain transitions in neonatal rats: importance of innervation and thyroid state

During the postnatal period, rat limb muscles adapt to weight bearing via the replacement of embryonic (Emb) and neonatal (Neo) myosin heavy chains (MHCs) by the adult isoforms. Our aim was to characterize this transition in terms of the six MHC isoforms expressed in skeletal muscle and to determine the importance of innervation and thyroid hormone status on the attainment of the adult MHC phenotype. Neonatal rats were made hypothyroid via propylthiouracil (PTU) injection. In normal and PTU subgroups, leg muscles were unilaterally denervated at 15 days of age. The MHC profiles of plantaris (PLN) and soleus (Sol) muscles were determined at 7, 14, 23, and 30 days postpartum. At day 7, the Sol MHC profile was 55% type I, 30% Emb, and 10% Neo; in the PLN, the pattern was 60% Neo and 25% Emb. By day 30 the Sol and PLN had essentially attained an adult MHC profile in the controls. PTU augmented slow MHC expression in the Sol, whereas in the PLN it markedly repressed IIb MHC by retaining neonatal MHC expression. Denervation blunted the upregulation of IIb in the PLN and of Type I in the Sol and shifted the pattern to greater expression of IIa and IIx MHCs in both muscles. In contrast to previous observations, these findings collectively suggest that both an intact thyroid and innervation state are obligatory for the attainment of the adult MHC phenotype, particularly in fast-twitch muscles.

Non-NASA Center↗
NASA NTRS1999

Bone and hormonal changes induced by skeletal unloading in the mature male rat

To determine whether the rat hindlimb elevation model can be used to study the effects of spaceflight and loss of gravitational loading on bone in the adult animal, and to examine the effects of age on bone responsiveness to mechanical loading, we studied 6-mo-old rats subjected to hindlimb elevation for up to 5 wk. Loss of weight bearing in the adult induced a mild hypercalcemia, diminished serum 1,25-dihydroxyvitamin D, decreased vertebral bone mass, and blunted the otherwise normal increase in femoral mass associated with bone maturation. Unloading decreased osteoblast numbers and reduced periosteal and cancellous bone formation but had no effect on bone resorption. Mineralizing surface, mineral apposition rate, and bone formation rate decreased during unloading. Our results demonstrate the utility of the adult rat hindlimb elevation model as a means of simulating the loss of gravitational loading on the skeleton, and they show that the effects of nonweight bearing are prolonged and have a greater relative effect on bone formation in the adult than in the young growing animal.

NASA Discipline Musculoskeletal↗
NASA NTRS2009

Homocysteine and Cognitive Performance in Elders with Self-Neglect

Elevated plasma homocysteine has been associated with altered cognitive performance in older adults. Elders referred to Adult Protective Services (APS) for self-neglect have been reported to have elevated plasma homocysteine levels and to suffer from cognitive impairment. This study assesses the association, if any, between plasma homocysteine and cognitive performance among elders with self-neglect. Methods: Sixty-five community-living adults, 65 years of age and older, reported to Adult Protective Services for self-neglect and 55 matched controls (matched for age, ethnicity, gender and socio-economic status) consented and participated in this study. The research team conducted in-home comprehensive geriatric assessments which included the mini-mental state exam (MMSE), the 15-item geriatric depression scale (GDS), the Wolf-Klein Clock Drawing Tests (CDT) and a comprehensive nutritional biochemistry panel, which included plasma homocysteine. Student s t tests and Pearson correlations were conducted to assess for bivariate associations. Results: Elders with self-neglect had significantly higher plasma homocysteine levels (M=12.68umol/L, sd=4.4) compared to the controls (M=10.40umol/L, sd=3.61;t=3.21, df=127, p=.002). There were no statistically significant associations between cognitive performance and plasma homocysteine in the self-neglect group, however there was a significant correlation between plasma homocysteine and the CDT among the controls (r=-.296, p=.022). Conclusion: Mean plasma homocysteine levels were significantly higher in elders with self-neglect, however, they do not appear to be related to cognitive performance, indicating that cognitive impairment in elder self-neglect involve mechanisms other than hyperhomocysteinemia. These findings warrant further investigation

Burnett, J.↗
NASA NTRS2016

Sex-specific Effects of Unpredictable Variable Prenatal Stress: Implications for Mammalian Developmental Programming During Spaceflight

During initial exposure and adaptation to the microgravity environment, adult mammals exhibit elevated stress, mediated by the Hypothalamic-Pituitary-Adrenal (HPA) axis. In our previous studies of pregnant rats exposed to 2-g hypergravity via continuous centrifugation, we reported changes in neuroendocrine profiles including decreased corticosterone and a concomitant increase in body mass and leptin in adult male offspring. Prenatally stressed adult offspring have been shown to exhibit an elevated stress response in adulthood, therefore we hypothesized that these changes resulted from stress exposure during fetal development. Future studies examining reproduction, gestation, and development on-orbit need to consider the unique stressors of vehicle launch, the space environment, and landing on the development of the HPA axis in animals born and raised in microgravity. In this study, we utilize Unpredictable Variable Prenatal Stress (UVPS) to simulate the stressors of spaceflight by exposing dams to three different stressors: (1) White Noise, (2) Strobe Light, and (3) Tube Restraint. Stressors were applied from Gestational Day 0 (G0), following an unpredictable schedule (morning [0600-1200hrs]; afternoon [1200-1800hrs]; evening [1800-2400hrs] in 15, 30, or 60 minute durations alongside non-stressed (NS) control dams. Following parturition, pups were fostered to non-manipulated, newly parturient dams to control for differential maternal care. On postnatal day 90 (P90), we harvested the hypothalamus, pituitary, and adrenal glands, and analyzed mRNA expression of the following genes via RT-qPCR: 1) melanocortin-2 receptor (MC2R), POMC, corticotropin-releasing hormone (CRH) in the pituitary; 2) glucocorticoid receptor (NR3C1), pro-opiomelanocortin (POMC), corticotropin-releasing hormone (CRH), brain-derived neurotropic factor (BDNF), in the hypothalamus; and 3) MC2R, tyrosine hydroxylase (TH), steroidogenic acute regulatory protein (STAR), cytochrome P450scc enzyme (CYP) in the adrenal. The identification of sex-specific fetal programming effects on adult stress response is a key step in determining potential animal behavior on-orbit, and will guide future multi-generational studies in microgravity.

prenatal stress↗
NASA NTRSDate not supplied

NSCOR for Evaluating Risk Factors and Biomarkers for Adaptation and Resilience to Spaceflight: Emotional Valence and Social Processes in ICC/ICE Environments

Space exploration class missions, such as a mission to Mars, will require optimization of human performance, adaptability, and resilience. This NASA Specialized Center of Research (NSCOR) utilizes the NIMH Research Domain Criteria (RDoC) framework to identify biological and behavioral markers of individual social adaptation and emotional resilience (as well as vulnerability) to spaceflight-relevant stressors such as living in extended isolation. The overarching goal of this NSCOR is to obtain novel information to help identify biomarkers of individuals who are resilient and/or adaptable to the stressors of isolated, confined, and controlled (ICC) and isolated, confined, and extreme (ICE) environments.A total of N=90 healthy adult astronaut surrogates are being studied in three spaceflight-analog environments: (1) n=40 healthy adults in the Isolation and Confinement Analog Research Unit (ICARUS), an ICC at the University of Pennsylvania, during 7-day missions, for a target total of 280 subject days; (2) n=32 healthy adult astronaut surrogates studied in NASA’s Human Exploration Research Analog (HERA), an ICC at Johnson Space Center during 45-day missions, for a target total of 2,112 subject days; and (3) n=18 healthy adults in the Alfred-Wegener-Institute’s Neumayer Station III, an ICE in Antarctica, during 14-month missions, for a target total of 7,560 subject days. Dr. Nindl’s Laboratory at the University of Pittsburgh is analyzing a priori selected protein biomarkers in blood, saliva, and urine. Complementary rodent models of exposure to early life stressors, confinement, and isolation are being evaluated at Dr. Hensch’s Laboratory to further validate the neurobehavioral and biological findings from the human studies.Given the inconsistency and varied definition of resilience/adaptation in the scientific literature, the NSCOR team developed a composite resilience/adaptation measure that reflects the most relevant outcomes to resilience/adaptation across psychosocial and neurobehavioral functions, as well as neurocognitive and spaceflight-relevant operational performance. To achieve this, group consensus was attained from subject matter experts to produce a rank-order of importance for each input variable. The final resilience/adaptation score included 36 variables that were collected across spaceflight analogs. As of 10/1/2021, the NSCOR project acquired data on n=27 subjects at ICARUS, n=16 at HERA, and n=18 at Neumayer. The COVID-19 pandemic delayed data acquisition at ICARUS and HERA.Among subjects studied to date, 99% of neural and neurobehavioral data (e.g., neuroimaging for structure and function, behavioral measures) as well as blood, saliva, and urine for biochemical assays have been acquired. For rodent models, Dr. Hensch’s laboratory has established biochemical and behavioral parameters reflecting confinement stress in social networks of mice for comparison to stress responses in the human spaceflight analog environments.Group social behaviors were measured with a Social Network Analysis (SNA) approach to define objective parameters associated with sociability and its plasticity by sex. This analytic approach may help identify a network of individuals who are more effective teammates or more likely to generate new social relationships. Data acquisition, biomarker assessment, and data quality control will continue through September 2022.

D F Dinges↗
NASA NTRS1999

Relationship of endogenous circadian melatonin and temperature rhythms to self-reported preference for morning or evening activity in young and older people

BACKGROUND: Morningness-eveningness refers to interindividual differences in preferred timing of behavior (i.e., bed and wake times). Older people have earlier wake times and rate themselves as more morning-like than young adults. It has been reported that the phase of circadian rhythms is earlier in morning-types than in evening types, and that older people have earlier phases than young adults. These changes in phase have been considered to be the chronobiological basis of differences in preferred bed and wake times and age-related changes therein. Whether such differences in phase are associated with changes in the phase relationship between endogenous circadian rhythms and the sleep-wake cycle has not been investigated previously. METHODS: We investigated the association between circadian phase, the phase relationship between the sleep-wake cycle and circadian rhythms, and morningness-eveningness, and their interaction with aging. In this circadian rhythm study, 68 young and 40 older subjects participated. RESULTS: Among the young subjects, the phase of the melatonin and core temperature rhythms occurred earlier in morning than in evening types and the interval between circadian phase and usual wake time was longer in morning types. Thus, while evening types woke at a later clock hour than morning types, morning types actually woke at a later circadian phase. Comparing young and older morning types we found that older morning types had an earlier circadian phase and a shorter phase-wake time interval. The shorter phase-waketime interval in older "morning types" is opposite to the change associated with morningness in young people, and is more similar to young evening types. CONCLUSIONS: These findings demonstrate an association between circadian phase, the relationship between the sleep-wake cycle and circadian phase, and morningness-eveningness in young adults. Furthermore, they demonstrate that age-related changes in phase angle cannot be attributed fully to an age-related shift toward morningness. These findings have important implications for understanding individual preferences in sleep-wake timing and age-related changes in the timing of sleep.

Non-NASA Center↗
NASA NTRS1998

Self-reported coping behavior in health and disease: assessment with a card sort game

The authors tested the hypothesis that individuals with a variety of severe chronic illnesses and the healthy elderly exhibit a loss of flexibility in their response to a variety of stressors, compared with healthy adults. A card sort game designed to assess self-reported coping behavior under different stressful life situations was used to compare healthy adults with individuals with multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, and the elderly. The healthy adults were found to exhibit more variability than any of the illness groups or the elderly. Healthy function is marked by a complex type of variability.

Non-NASA Center↗
DOE OSTI2024

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↗