Reparation and Reconciliationis the first book to reveal the nineteenth-century struggle for racial integration on U.S. college campuses. As the Civil War ended, the need to heal the scars of ...slavery, expand the middle class, and reunite the nation engendered a dramatic interest in higher education by policy makers, voluntary associations, and African Americans more broadly. Formed in 1846 by Protestant abolitionists, the American Missionary Association united a network of colleges open to all, designed especially to educate African American and white students together, both male and female. The AMA and its affiliates envisioned integrated campuses as a training ground to produce a new leadership class for a racially integrated democracy. Case studies at three colleges--Berea College, Oberlin College, and Howard University--reveal the strategies administrators used and the challenges they faced as higher education quickly developed as a competitive social field.Through a detailed analysis of archival and press data, Christi M. Smith demonstrates that pressures between organizations--including charities and foundations--and the emergent field of competitive higher education led to the differentiation and exclusion of African Americans, Appalachian whites, and white women from coeducational higher education and illuminates the actors and the strategies that led to the persistent salience of race over other social boundaries.
Sensory perception modulates aging, yet we know little about how. An understanding of the neuronal mechanisms through which animals orchestrate biological responses to relevant sensory inputs would ...provide insight into the control systems that may be important for modulating lifespan. Here, we provide new awareness into how the perception of dead conspecifics, or death perception, which elicits behavioral and physiological effects in many different species, affects lifespan in the fruit fly, Drosophila melanogaster. Previous work demonstrated that cohousing Drosophila with dead conspecifics decreases fat stores, reduces starvation resistance, and accelerates aging in a manner that requires both sight and the serotonin receptor 5-HT2A. In this manuscript, we demonstrate that a discrete, 5-HT2A-expressing neural population in the ellipsoid body (EB) of the Drosophila central complex, identified as R2/R4 neurons, acts as a rheostat and plays an important role in transducing sensory information about the presence of dead individuals to modulate lifespan. Expression of the insulin-responsive transcription factor foxo in R2/R4 neurons and insulin-like peptides dilp3 and dilp5, but not dilp2, are required, with the latter likely altered in median neurosecretory cells (MNCs) after R2/R4 neuronal activation. These data generate new insights into the neural underpinnings of how perceptive events may impact aging and physiology across taxa.
Sensory perception modulates health and aging across taxa. Understanding the nature of relevant cues and the mechanisms underlying their action may lead to novel interventions that improve the length ...and quality of life. We found that in the vinegar fly, Drosophila melanogaster, exposure to dead conspecifics in the environment induced cues that were aversive to other flies, modulated physiology, and impaired longevity. The effects of exposure to dead conspecifics on aversiveness and lifespan required visual and olfactory function in the exposed flies. Furthermore, the sight of dead flies was sufficient to produce aversive cues and to induce changes in the head metabolome. Genetic and pharmacologic attenuation of serotonergic signaling eliminated the effects of exposure on aversiveness and lifespan. Our results indicate that Drosophila have an ability to perceive dead conspecifics in their environment and suggest conserved mechanistic links between neural state, health, and aging; the roots of which might be unearthed using invertebrate model systems.
This work describes the NASA Atmospheric CO2 Observations from Space (ACOS) XCO2 retrieval algorithm, and its performance on highly realistic, simulated observations. These tests, restricted to ...observations over land, are used to evaluate retrieval errors in the face of realistic clouds and aerosols, polarized non-Lambertian surfaces, imperfect meteorology, and uncorrelated instrument noise. We find that post-retrieval filters are essential to eliminate the poorest retrievals, which arise primarily due to imperfect cloud screening. The remaining retrievals have RMS errors of approximately 1 ppm. Modeled instrument noise, based on the Greenhouse Gases Observing SATellite (GOSAT) in-flight performance, accounts for less than half the total error in these retrievals. A small fraction of unfiltered clouds, particularly thin cirrus, lead to a small positive bias of ~0.3 ppm. Overall, systematic errors due to imperfect characterization of clouds and aerosols dominate the error budget, while errors due to other simplifying assumptions, in particular those related to the prior meteorological fields, appear small.
Summary
MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression associated with many complex biological processes. By comparing miRNA expression between long‐lived cohorts of ...Drosophila melanogaster that were fed a low‐nutrient diet with normal‐lived control animals fed a high‐nutrient diet, we identified miR‐184, let‐7, miR‐125, and miR‐100 as candidate miRNAs involved in modulating aging. We found that ubiquitous, adult‐specific overexpression of these individual miRNAs led to significant changes in fat metabolism and/or lifespan. Most impressively, adult‐specific overexpression of let‐7 in female nervous tissue increased median fly lifespan by ~22%. We provide evidence that this lifespan extension is not due to alterations in nutrient intake or to decreased insulin signaling.
Background:
Osimertinib is the cornerstone in the treatment of epidermal growth factor receptor-mutated non-small cell lung cancer (NSCLC). Nonetheless, ±25% of patients experience severe ...treatment-related toxicities. Currently, it is impossible to identify patients at risk of severe toxicity beforehand. Therefore, we aimed to study the relationship between osimertinib exposure and severe toxicity and to identify a safe toxic limit for a preventive dose reduction.
Methods:
In this real-life prospective cohort study, patients with NSCLC treated with osimertinib were followed for severe toxicity (grade ⩾3 toxicity, dose reduction or discontinuation, hospital admission, or treatment termination). Blood for pharmacokinetic analyses was withdrawn during every out-patient visit. Primary endpoint was the correlation between osimertinib clearance (exposure) and severe toxicity. Secondary endpoint was the exposure–efficacy relationship, defined as progression-free survival (PFS) and overall survival (OS).
Results:
In total, 819 samples from 159 patients were included in the analysis. Multivariate competing risk analysis showed osimertinib clearance (c.q. exposure) to be significantly correlated with severe toxicity (hazard ratio 0.93, 95% CI: 0.88–0.99). An relative operating characteristic curve showed the optimal toxic limit to be 259 ng/mL osimertinib. A 50% dose reduction in the high-exposure group, that is 25.8% of the total cohort, would reduce the risk of severe toxicity by 53%. Osimertinib exposure was not associated with PFS nor OS.
Conclusion:
Osimertinib exposure is highly correlated with the occurrence of severe toxicity. To optimize tolerability, patients above the toxic limit concentration of 259 ng/mL could benefit from a preventive dose reduction, without fear for diminished effectiveness.
Cognitive function declines with age throughout the animal kingdom, and increasing evidence shows that disruption of the proteasome system contributes to this deterioration. The proteasome has ...important roles in multiple aspects of the nervous system, including synapse function and plasticity, as well as preventing cell death and senescence. Previous studies have shown neuronal proteasome depletion and inhibition can result in neurodegeneration and cognitive deficits, but it is unclear if this pathway is a driver of neurodegeneration and cognitive decline in aging. We report that overexpression of the proteasome β5 subunit enhances proteasome assembly and function. Significantly, we go on to show that neuronal‐specific proteasome augmentation slows age‐related declines in measures of learning, memory, and circadian rhythmicity. Surprisingly, neuronal‐specific augmentation of proteasome function also produces a robust increase of lifespan in Drosophila melanogaster. Our findings appear specific to the nervous system; ubiquitous proteasome overexpression increases oxidative stress resistance but does not impact lifespan and is detrimental to some healthspan measures. These findings demonstrate a key role of the proteasome system in brain aging.
Proteasome function declines in the nervous system over the course of age. Overexpression of the proteasome β5 subunit increases whole proteasome assembly. Increased neuronal‐specific proteasome assembly extends lifespan and reduces age‐related cognitive deficits. Elevation of proteasome assembly in non‐neuronal tissues increases oxidative stress resistance but does not extend lifespan and is detrimental to some healthspan measures.
ABSTRACT
Ensuring Force Health Protection (FHP) is one of the most critical priorities in the DoD; however, there is no systematic approach for individual service members to address their own FHP. ...This paper outlines the FHP Education workshop, a model program fielded at 3rd Special Forces Group, Fort Bragg, NC, which applies military processes, principles, and frameworks to teaching special operations forces operators and enablers how to address their own FHP by identifying and mitigating threats to health and performance in the military operational environment. The FHP Education workshop has the potential to be a well-received and impactful program that offers a proactive, whole of person, community-based preventive system aligned with the Total Force Fitness framework to enable individual service members to conduct FHP.
Intimal hyperplasia and stenosis are often cited as causes of arteriovenous fistula maturation failure, but definitive evidence is lacking. We examined the associations among preexisting venous ...intimal hyperplasia, fistula venous stenosis after creation, and clinical maturation failure. The Hemodialysis Fistula Maturation Study prospectively observed 602 men and women through arteriovenous fistula creation surgery and their postoperative course. A segment of the vein used to create the fistula was collected intraoperatively for histomorphometric examination. On ultrasounds performed 1 day and 2 and 6 weeks after fistula creation, we assessed fistula venous stenosis using pre-specified criteria on the basis of ratios of luminal diameters and peak blood flow velocities at certain locations along the vessel. We determined fistula clinical maturation using criteria for usability during dialysis. Preexisting venous intimal hyperplasia, expressed per 10% increase in a hyperplasia index (range of 0%-100%), modestly associated with lower fistula blood flow rate (relative change, -2.5%; 95% confidence interval 95% CI, -4.6% to -0.4%;
=0.02) at 6 weeks but did not significantly associate with stenosis (odds ratio OR, 1.07; 95% CI, 1.00 to 1.16;
=0.07) at 6 weeks or failure to mature clinically without procedural assistance (OR, 1.07; 95% CI, 0.99 to 1.15;
=0.07). Fistula venous stenosis at 6 weeks associated with maturation failure (OR, 1.98; 95% CI, 1.25 to 3.12;
=0.004) after controlling for case mix factors, dialysis status, and fistula location. These findings suggest that postoperative fistula venous stenosis associates with fistula maturation failure. Preoperative venous hyperplasia may associate with maturation failure but if so, only modestly.
It is recommended that school-aged children accrue 30 minutes of daily moderate-to-vigorous physical activity (MVPA) in school. Current literature is inconclusive about the long-term associations ...between school-based physical activity and academic achievement. In this study, we use a large sample and longitudinal design to rigorously evaluate whether school-day MVPA is associated with academic achievement. In a diverse suburban public school district, 4936 Grade 4 students were recruited in 40 elementary schools. Students wore accelerometers to measure school-day MVPA for 15 days across three semesters. Academic performance data was collected across Grade 3 fall to Grade 5 spring, including teacher-assigned grades and standardized test scores. Multilevel modeling was conducted controlling for student demographics and school characteristics. Cross-sectional analyses found small negative associations in Grade 4. Grade 4 full-year mean daily school-day MVPA had beta = --0.066, beta = --0.063, beta = --0.066, and beta = --0.058 associations (p < 0.001) with Grade 4 math, reading, spelling, and writing grades respectively, and Grade 4 full-year mean daily school-day MVPA had beta = --0.206 and beta = --0.283 (p < 0.001) associations with Grade 4 math and English Language Arts (ELA) standardized test scores respectively out of approximately 500 points. Longitudinal analyses found no significant associations between Grade 4 full-year mean daily school-day MVPA and Grade 5 Fall course grades. Results also indicated small negative associations for students attaining 30+ minutes of daily school-day MVPA compared to those attaining less than 15 minutes, but only in Grade 4 Fall cross-sectional analyses where teacher-assigned reading, spelling, and writing grades were - 1.666, - 1.638, and - 1.993 points lower respectively (p < 0.001). The cross-sectional findings, while statistically significant in a negative direction, have a negligible association when translated practically. For example, even if students attained twice the recommended amount of school-day MVPA - which would constitute an approximately 300% increase from current levels - results suggest that grades would only decrease by 2 points on a 100-point scale. Furthermore, longitudinal analyses suggest school-day MVPA does not have a predictive association with course grades or standardized test scores. Findings suggest school-based MVPA implemented in accordance with recommendations does not meaningfully detract from academic progress.
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