Migration and genetic drift in human populations

Journal ArticleIn humans and many other species, mortality is concentrated early in the life cycle, and is low during the ages of dispersal and reproduction. Yet precisely the opposite is assumed by classical population-genetics models of migration and genetic drift. We introduce a model in which population regulation occurs before migration. In contrast to the conventional model, our model implies that geographic variation in the allele frequencies of newborns should exceed that of adults. Thus, it is important to distinguish genetic variation of adults from that of newborns in species with human-like life cycles

Detecting positive selection from genome scans of linkage disequilibrium

<p>Abstract</p> <p>Background</p> <p>Though a variety of linkage disequilibrium tests have recently been introduced to measure the signal of recent positive selection, the statistical properties of the various methods have not been directly compared. While most applications of these tests have suggested that positive selection has played an important role in recent human history, the results of these tests have varied dramatically.</p> <p>Results</p> <p>Here, we evaluate the performance of three statistics designed to detect incomplete selective sweeps, LRH and iHS, and ALnLH. To analyze the properties of these tests, we introduce a new computational method that can model complex population histories with migration and changing population sizes to simulate gene trees influenced by recent positive selection. We demonstrate that iHS performs substantially better than the other two statistics, with power of up to 0.74 at the 0.01 level for the variation best suited for full genome scans and a power of over 0.8 at the 0.01 level for the variation best suited for candidate gene tests. The performance of the iHS statistic was robust to complex demographic histories and variable recombination rates. Genome scans involving the other two statistics suffer from low power and high false positive rates, with false discovery rates of up to 0.96 for ALnLH. The difference in performance between iHS and ALnLH, did not result from the properties of the statistics, but instead from the different methods for mitigating the multiple comparison problem inherent in full genome scans.</p> <p>Conclusions</p> <p>We introduce a new method for simulating genealogies influenced by positive selection with complex demographic scenarios. In a power analysis based on this method, iHS outperformed LRH and ALnLH in detecting incomplete selective sweeps. We also show that the single-site iHS statistic is more powerful in a candidate gene test than the multi-site statistic, but that the multi-site statistic maintains a low false discovery rate with only a minor loss of power when applied to a scan of the entire genome. Our results highlight the need for careful consideration of multiple comparison problems when evaluating and interpreting the results of full genome scans for positive selection.</p

Adjustments and Uncertainty Quantification for SLS Aerodynamic Sectional Loads

This paper presents a method for adjusting sectional loads to match target values for integrated force and moment coefficients. In a typical application, the sectional load profile for one flight condition is calculated from Computational Fluid Dynamics (CFD) while the integrated forces and moments are measured in a wind tunnel experiment. These two methods do not generally result in identical predictions, and this leads to an inherent inconsistency between different data products. This paper aims to provide a procedure to remove that inconsistency. A sectional load profile for a launch vehicle splits the rocket into slices along its length and calculates the aerodynamic loading on each slice, which leads to a one-dimensional aerodynamic load profile that is used for structural analysis. Adjusting sectional loads, also known as line loads, is a nontrivial matter due to several consistency constraints. For example, the adjusted sectional normal force profile must be consistent with both the integrated normal force and pitching moment. To avoid such inconsistency issues, this paper presents a method using a Proper Orthogonal Decomposition (POD) to generate basis functions to adjust the sectional load profiles. As a corollary, this correction method enables the creation of an uncertainty quantification for sectional loads that is consistent with the dispersed integrated force and moment database and its uncertainty quantification. Several extensions to this technique, such as applying the method to the surface pressures, are considered

Inviscid and Viscous CFD Analysis of Booster Separation for the Space Launch System Vehicle

This paper presents details of Computational Fluid Dynamic (CFD) simulations of the Space Launch System during solid-rocket booster separation using the Cart3D inviscid and Overflow viscous CFD codes. The discussion addresses the use of multiple data sources of computational aerodynamics, experimental aerodynamics, and trajectory simulations for this critical phase of flight. Comparisons are shown between Cart3D simulations and a wind tunnel test performed at NASA Langley Research Center's Unitary Plan Wind Tunnel, and further comparisons are shown between Cart3D and viscous Overflow solutions for the flight vehicle. The Space Launch System (SLS) is a new exploration-class launch vehicle currently in development that includes two Solid Rocket Boosters (SRBs) modified from Space Shuttle hardware. These SRBs must separate from the SLS core during a phase of flight where aerodynamic loads are nontrivial. The main challenges for creating a separation aerodynamic database are the large number of independent variables (including orientation of the core, relative position and orientation of the boosters, and rocket thrust levels) and the complex flow caused by exhaust plumes of the booster separation motors (BSMs), which are small rockets designed to push the boosters away from the core by firing partially in the direction opposite to the motion of the vehicle

Impact of a Novel Adaptive Optimization Algorithm on 30-Day Readmissions Evidence From the Adaptive CRT Trial

AbstractObjectivesThis study investigated the impact of the Medtronic AdaptivCRT (aCRT) (Medtronic, Mounds View, Minnesota) algorithm on 30-day readmissions after heart failure (HF) and all-cause index hospitalizations.BackgroundThe U.S. Hospital Readmission Reduction Program, which includes a focus on HF, reduces Medicare inpatient payments when readmissions within 30 days of discharge exceed a moving threshold based on national averages and hospital-specific risk adjustments. Internationally, readmissions within 30 days of any discharge may attract reduced or no payment. Recently, cardiac resynchronization therapy (CRT) devices equipped with the aCRT algorithm allowing automated ambulatory device programming were introduced. The Adaptive CRT trial demonstrated the algorithm’s safety and comparable outcome against a rigorous echocardiography-based optimization protocol.MethodsWe analyzed data from the Adaptive CRT trial, which randomized patients undergoing CRT defibrillation on a 2:1 basis to aCRT (n = 318) or to CRT with echocardiographic optimization (Echo, n = 160) and followed up these patients for a mean of 20.2 months (range: 0.2 to 31.3 months). Logistic regression with generalized estimating equation methodology was used to compare the proportion of patients hospitalized for HF and for all causes who had a readmission within 30 days.ResultsFor HF hospitalizations, the 30-day readmission rate was 19.1% (17 of 89) in the aCRT group and 35.7% (15 of 42) in the Echo group (odds ratio: 0.41; 95% confidence interval [CI]: 0.19 to 0.86; p = 0.02). For all-cause hospitalization, the 30-day readmission rate was 14.8% (35 of 237) in the aCRT group compared with 24.8% (39 of 157) in the Echo group (odds ratio: 0.54; 95% CI: 0.31 to 0.94; p = 0.03). The risk of readmission after HF or all-cause index hospitalization with aCRT was also significantly reduced beyond 30 days.ConclusionsUse of the aCRT algorithm is associated with a significant reduction in the probability of a 30-day readmission after both HF and all-cause hospitalizations. (Adaptive Cardiac Resynchronization Therapy Study [aCRT]; NCT00980057

Comparison of Space Launch System Aerodynamic Surface Pressure Measurements from Experimental Testing and CFD

A comparison of surface pressure coefficient measurements obtained using pressure-sensitive paint (PSP) measurements with predictions from the computational fluid dynamics (CFD) code FUN3D is presented for the NASA SLS Block 1B crew vehicle. Overall, the flow features over the SLS configuration were captured by both the PSP data and CFD data at freestream Mach numbers (M(sub )) of 0.8 and 1.3. Overall, the flow features over the SLS are captured by the PSP data but the intensities of large pressure gradients are less intense than what was predicted by the CFD data. Several examples of this observation are given including the flow interaction at the booster nose cone edge, core body, and forward booster attachment hardware at M(sub ) = 0.8

Adjustments and Uncertainty Quantification for SLS Aerodynamic Sectional Loads

No abstract availabl

The Spitzer search for the transits of HARPS low-mass planets - I. No transit for the super-Earth HD 40307b

We have used Spitzer and its IRAC camera to search for the transit of the super-Earth HD 40307b. The transiting nature of the planet could not be firmly discarded from our first photometric monitoring of a transit window because of the uncertainty coming from the modeling of the photometric baseline. To obtain a firm result, two more transit windows were observed and a global Bayesian analysis of the three IRAC time series and the HARPS radial velocities was performed. Unfortunately, any transit of the planet during the observed phase window is firmly discarded, while the probability that the planet transits but that the eclipse was missed by our observations is nearly negligible (0.26%).Comment: Submitted to A&

Ascent Aerodynamic Force and Moment Database Development for the Space Launch System

The Space Launch System Aerodynamics Task Team is responsible for delivering aerodynamic force and moment databases from liftoff through ascent until the rocket leaves the Earths atmosphere. The process for developing the ascent portion of this database is described in the current paper. The data used to develop the database were generated using a combination of wind tunnel testing and CFD simulations. The details of the wind tunnel testing performed at the NASA Ames Unitary Plan Wind Tunnel and CFD simulations performed using FUN3D at wind tunnel and flight conditions are discussed, and comparisons of these data sets are provided. The methods used for converting the source data into the final database response surfaces with corresponding uncertainty are also detailed