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Efforts to identify the genetic basis of human adaptations from polymorphism data have sought footprints of \"classic selective sweeps\" (in which a beneficial mutation arises and rapidly fixes in the population).Yet it remains unknown whether this form of natural selection was common in our evolution. We examined the evidence for classic sweeps in resequencing data from 179 human genomes. As expected under a recurrent-sweep model, we found that diversity levels decrease near exons and conserved noncoding regions. In contrast to expectation, however, the trough in diversity around human-specific amino acid substitutions is no more pronounced than around synonymous substitutions. Moreover, relative to the genome background, amino acid and putative regulatory sites are not significantly enriched in alleles that are highly differentiated between populations. These findings indicate that classic sweeps were not a dominant mode of human adaptation over the past approximately 250,000 years.

We describe the design and performance of the near-infrared (1.51-1.70 m), fiber-fed, multi-object (300 fibers), high resolution (R = λ/Δλ ∼ 22,500) spectrograph built for the Apache Point Observatory Galactic Evolution Experiment (APOGEE). APOGEE is a survey of ∼105 red giant stars that systematically sampled all Milky Way populations (bulge, disk, and halo) to study the Galaxy's chemical and kinematical history. It was part of the Sloan Digital Sky Survey III (SDSS-III) from 2011 to 2014 using the 2.5 m Sloan Foundation Telescope at Apache Point Observatory, New Mexico. The APOGEE-2 survey is now using the spectrograph as part of SDSS-IV, as well as a second spectrograph, a close copy of the first, operating at the 2.5 m du Pont Telescope at Las Campanas Observatory in Chile. Although several fiber-fed, multi-object, high resolution spectrographs have been built for visual wavelength spectroscopy, the APOGEE spectrograph is one of the first such instruments built for observations in the near-infrared. The instrument's successful development was enabled by several key innovations, including a \"gang connector\" to allow simultaneous connections of 300 fibers; hermetically sealed feedthroughs to allow fibers to pass through the cryostat wall continuously; the first cryogenically deployed mosaic volume phase holographic grating; and a large refractive camera that includes mono-crystalline silicon and fused silica elements with diameters as large as ∼400 mm. This paper contains a comprehensive description of all aspects of the instrument including the fiber system, optics and opto-mechanics, detector arrays, mechanics and cryogenics, instrument control, calibration system, optical performance and stability, lessons learned, and design changes for the second instrument.

A steady rise in fires in the Western United States, coincident with intensifying droughts, imparts substantial modifications to the underlying vegetation, hydrology and overall ecosystem. Drought can compound the ecosystem disturbance caused by fire, although how these compound effects on hydrologic and ecosystem recovery vary among ecosystems is poorly understood. Here we use remote sensing-derived high-resolution evapotranspiration (ET) estimates from before and after 1,514 fires to show that ecoregions dominated by grasslands and shrublands are more susceptible to drought, which amplifies fire-induced ET decline and, subsequently, shifts water flux partitioning. In contrast, severely burned forests recover from fire slowly or incompletely, but are less sensitive to dry extremes. We conclude that moisture limitation caused by droughts influences the dynamics of water balance recovery in post-fire years. This finding explains why moderate to extreme droughts aggravate impacts on the water balance in non-forested vegetation, while moisture accessed by deeper roots in forests helps meet evaporative demands unless severe burns disrupt internal tree structure and deplete fuel load availability. Our results highlight the dominant control of drought on altering the resilience of vegetation to fires, with critical implications for terrestrial ecosystem stability in the face of anthropogenic climate change in the West. The authors compare how grasslands, shrublands and forests differ in their capacity to recover from fires, and how this recovery depends on deviations in water balance caused by drought; they show that the compound effects of fire and drought are less impactful in forests than in non-forests, owing to deeper rooting structures that can maintain access to water.

Background A relationship between intracranial and abdominal aortic aneurysms (AAA) has been appreciated through genome-wide association studies suggesting a shared pathophysiology. However, the actual prevalence of AAA in patients presenting with ruptured intracranial aneurysms is not known. Our aim was to estimate the prevalence of previously undiagnosed AAA in patients presenting with aneurysmal subarachnoid hemorrhage (aSAH) to see if it may be high enough to justify formally testing the utility of screening. Methods A prospective, observational inception cohort study of 81 consecutive patients presenting to Mayo Clinic Florida with aSAH was performed from August 14, 2011 to February 10, 2014. These individuals were then screened using an abdominal ultrasound technique for an AAA. Our primary end point was detection of AAA. Our secondary end points were 30-day good-to-fair functional status (modified Rankin scale < 4) and all-cause mortality. Results We detected an AAA in 10 patients (rate: 12%; 95% CI 6–22%) with aSAH. The mean diameter of these AAA was 3.4 ± 1.0 cm. Among these 10 patients, there was one death within the first month of aSAH hospitalization. There were no significant differences in demographic or clinical characteristics based on AAA detection status. Mean follow-up time was 4.7 years. The rate of good-to-fair functional status at 30-days was 79%. All-cause mortality during follow-up at 1-year was higher for patients with AAA (36%; 95% CI 0–61%) compared to patients without AAA (7%; 95% CI 1–14%) (log-rank p  = 0.045). Conclusions The co-prevalence of AAA in patients presenting with ruptured brain aneurysms may be sufficiently high such that screening for AAA among likely survivors of aSAH might be appropriate. Larger studies would be needed to establish a net clinical benefit from screening AAA and then treating newly identified large AAAs in this morbid population.

The dynamic behavior of proteins in crystals is examined by comparing theory and experiments. The Gaussian network model (GNM) and a simplified version of the crystallographic translation libration screw (TLS) model are used to calculate mean square fluctuations of C α atoms for a set of 113 proteins whose structures have been determined by x-ray crystallography. Correlation coefficients between the theoretical estimations and experiment are calculated and compared. The GNM method gives better correlation with experimental data than the rigid-body libration model and has the added benefit of being able to calculate correlations between the fluctuations of pairs of atoms. By incorporating the effect of neighboring molecules in the crystal the correlation is further improved.

Remotely sensed evapotranspiration (ET) data offer strong potential to support data-driven approaches for sustainable water management. However, practitioners require robust and rigorous accuracy assessments of such data. The OpenET system, which includes an ensemble of six remote sensing models, was developed to increase access to field-scale (30 m) ET data for the contiguous United States. Here we compare OpenET outputs against data from 152 in situ stations, primarily eddy covariance flux towers, deployed across the contiguous United States. Mean absolute error at cropland sites for the OpenET ensemble value is 15.8 mm per month (17% of mean observed ET), mean bias error is −5.3 mm per month (6%) and r 2 is 0.9. Results for shrublands and forested sites show higher inter-model variability and lower accuracy relative to croplands. High accuracy and multi-model convergence across croplands demonstrate the utility of a model ensemble approach, and enhance confidence among ET data practitioners, including the agricultural water resource management community.

Characterization of model errors is important when applying satellite-driven evapotranspiration (ET) models to water resource management problems. This study examines how uncertainty in meteorological forcing data and land surface modeling propagate through to errors in final ET data calculated using the Satellite Irrigation Management Support (SIMS) model, a computationally efficient ET model driven with satellite surface reflectance values. The model is applied to three instrumented winegrape vineyards over the 2017–2020 time period and the spatial and temporal variation in errors are analyzed. We illustrate how meteorological data inputs can introduce biases that vary in space and at seasonal timescales, but that can persist from year to year. We also observe that errors in SIMS estimates of land surface conductance can have a particularly strong dependence on time of year. Overall, meteorological inputs introduced RMSE of 0.33–0.65 mm/day (7–27%) across sites, while SIMS introduced RMSE of 0.55–0.83 mm/day (19–24%). The relative error contribution from meteorological inputs versus SIMS varied across sites; errors from SIMS were larger at one site, errors from meteorological inputs were larger at a second site, and the error contributions were of equal magnitude at the third site. The similar magnitude of error contributions is significant given that many satellite-driven ET models differ in their approaches to estimating land surface conductance, but often rely on similar or identical meteorological forcing data. The finding is particularly notable given that SIMS makes assumptions about the land surface (no soil evaporation or plant water stress) that do not always hold in practice. The results of this study show that improving SIMS by eliminating these assumptions would result in meteorological inputs dominating the error budget of the model on the whole. This finding underscores the need for further work on characterizing spatial uncertainty in the meteorological forcing of ET.

This research assessed the potential of increasing PUFA concentrations and the effect on flavor volatiles in red meat by feeding ground, full-fat soybean supplemented in casein complex. Supplements consisted of untreated ground, full-fat soybean (CO) or ground, full-fat soybeans treated with acetaldehyde (AC) or diacetyl (DA) to form gels. On a DM basis, the control (CO), AC, and DA supplements contained 48.6, 50.0, and 49.1% CP and 17.3, 17.3, and 17.4% fat, respectively. Weaned feeder lambs (n = 18) were divided into three treatment groups with two pens of three lambs per group. One of three supplements (200 g of DM) plus 1 kg DM of a ground corn basal diet and 0.36 kg DM of grass hay was fed daily to each of six lambs in a group for 9 wk. Samples of the intramuscular (LM), intermuscular, subcutaneous, and kidney fat were obtained from each lamb carcass for determination of total lipid contents and fatty acid profiles. Flavor volatiles of broiled LM were also analyzed. Total fat content of the LM was 3.7, 4.6, and 2.6% for lambs consuming diets supplemented with CO, AC, and DA, respectively. Compared with lambs fed the untreated supplement (CO), lambs supplemented with AC or DA had 1) higher (P < 0.05) concentrations of linoleic (4.80 vs. 6.37 or 6.80%) and linolenic (0.28 vs. 0.43 or 0.45%) acids in the LM nonpolar lipids; 2) a higher (P < 0.05) concentration of linoleic acid (22.1 vs. 27.1 or 25.6%), but a lower (P < 0.05) concentration of oleic acid (17.2 vs. 13.0 or 13.1%), in the LM polar lipids; 3) a higher (P < 0.05) concentration of linoleic acid (3.77 vs. 6.13 or 6.06%) in subcutaneous fat; and 4) higher (P < 0.05) concentrations of linoleic (4.46 vs. 7.65 or 7.13%), linolenic (0.50 vs. 0.85 or 0.80%), and stearic (24.9 vs. 27.2 or 26.9%) acids, but a lower (P < 0.05) concentration of oleic acid (39.1 vs. 35.4 or 36.3%), in kidney fat. In broiled LM chops, 21 volatiles were identified, including seven alkanals, seven 2-alkenals, two 2,4-alkadienals, and five other compounds, but most differences in the volatile concentrations among lambs fed the different supplements did not correspond to concentration differences in their precursor fatty acids. Results indicated that compared with the untreated supplement (CO), AC and DA supplements protected linoleic (C 18:2n6) and linolenic (C18:3n3) acids in soybean oil from degradation in the rumen of the lambs, resulting in increased deposition in the muscle and adipose tissues of lamb.

Purpose of review Overdose deaths have increased significantly over the last 5 years. This review analyzes the severity and nature of the epidemic, its impact on society, factors driving the increase in mortality, special populations disproportionately affected, and solutions to decrease overdose deaths. A thorough understanding of opioid overdose rates and deaths position the reader to respond most effectively in their sphere of influence. Recent findings Final statistics for 2017 show a continued worsening of the epidemic. Recent studies focus on the evolving role of synthetic fentanyl, risk factors for fatal overdose, variation of mortality across demographic and socioeconomic regions, and the effectiveness of harm reduction strategies such as naloxone. Summary The national overdose death rate continues to rise unabated with a 9.6% increase during 2017, with an estimated cost over $550 billion in 2019. There are, however, effective strategies to identify and treat individuals at risk for a fatal overdose. The root cause of addiction is the brain’s response to despair, social stressors, and societal structural inequities. It is unlikely we will see a significant decrease in addiction and its consequences until these root causes are addressed. Additional research is needed on the role of social determinants in addiction, strategies to treat incarcerated individuals, the role of suicidal ideation in fatal overdose, and risk factors, and frequency of non-fatal overdose.

Growth inhibition of established tumor metastases in the lungs poses a difficult challenge for most clinical settings in spite of extensive multi-modality approaches. Aerosol delivery of drugs and genes holds promise for the treatment of disseminated lung metastases, since aerosol delivery can target the lungs specifically and uniformly. We previously demonstrated that aerosol delivery of dilauroylphosphatidylcholine liposome formulation of 9-nitrocamptothecin (9NC-DLPC) inhibits B16-F10 melanoma lung metastases. Aerosol delivery of polyethleneimine-p53 DNA (PEI-p53) complexes results in a similar anti-tumor effect in the B16-F10 model. In both these previous studies, the protocols were designed to inhibit development of lung metastases. In this study we demonstrate, using the B16-F10 melanoma lung metastasis model, that sequential aerosol delivery of PEI-p53 and 9NC-DLPC acts additively to inhibit growth of established B16-F10 tumor metastases in the lungs. Mice injected with B16-F10 cells and treated with a combination of 9NC-DLPC (twice weekly) and PEI-p53 (once weekly) aerosol complexes starting on day 11 after tumor inoculation, exhibited a highly significant (P < 0.01) reduction in the number of visible tumor foci as compared with untreated mice or mice treated with either single agent alone, or with a combination of 9NC and a control plasmid. There was a highly significant reduction in the tumor burden, as well as the lung weights for the 9NC and p53 combination group (P < 0.001 as compared with other groups). Moreover, the doses of p53 gene and 9NC in the combination group were reduced at least two-fold as compared with our previous single agent studies, but still achieved significant tumor inhibition. Furthermore, the sequential aerosol delivery of p53 and 9NC lead to a 30-40% increase in the mean survival time of these mice, as compared with animals in different control groups. The data suggest that the combination of 9NC and p53 gene delivered by aerosol is an attractive strategy for growth inhibition of established tumor metastases in the lungs.