Tumor mutational burden (TMB) measurements aid in identifying patients who are likely to benefit from immunotherapy; however, there is empirical variability across panel assays and factors ...contributing to this variability have not been comprehensively investigated. Identifying sources of variability can help facilitate comparability across different panel assays, which may aid in broader adoption of panel assays and development of clinical applications.
Twenty-nine tumor samples and 10 human-derived cell lines were processed and distributed to 16 laboratories; each used their own bioinformatics pipelines to calculate TMB and compare to whole exome results. Additionally, theoretical positive percent agreement (PPA) and negative percent agreement (NPA) of TMB were estimated. The impact of filtering pathogenic and germline variants on TMB estimates was assessed. Calibration curves specific to each panel assay were developed to facilitate translation of panel TMB values to whole exome sequencing (WES) TMB values.
Panel sizes >667 Kb are necessary to maintain adequate PPA and NPA for calling TMB high versus TMB low across the range of cut-offs used in practice. Failure to filter out pathogenic variants when estimating panel TMB resulted in overestimating TMB relative to WES for all assays. Filtering out potential germline variants at >0% population minor allele frequency resulted in the strongest correlation to WES TMB. Application of a calibration approach derived from The Cancer Genome Atlas data, tailored to each panel assay, reduced the spread of panel TMB values around the WES TMB as reflected in lower root mean squared error (RMSE) for 26/29 (90%) of the clinical samples.
Estimation of TMB varies across different panels, with panel size, gene content, and bioinformatics pipelines contributing to empirical variability. Statistical calibration can achieve more consistent results across panels and allows for comparison of TMB values across various panel assays. To promote reproducibility and comparability across assays, a software tool was developed and made publicly available.
•Estimation of TMB varies across different panels, with panel size, gene content and bioinformatics pipelines contributing to empirical variability.•Panel sizes greater than 667Kb are necessary to maintain adequate PPA and NPA for calling TMB high versus TMB low across the range of cutoffs used in practice.•Statistical calibration can achieve more consistent results across panels and allows for comparison of TMB values across various panel assays.
Abstract
We analyze 5108 AFGKM stars with at least five high-precision radial velocity points, as well as Gaia and Hipparcos astrometric data, utilizing a novel pipeline developed in previous work. ...We find 914 radial velocity signals with periods longer than 1000 days. Around these signals, 167 cold giants and 68 other types of companions are identified, through combined analyses of radial velocity, astrometry, and imaging data. Without correcting for detection bias, we estimate the minimum occurrence rate of the wide-orbit brown dwarfs to be 1.3%, and find a significant brown-dwarf valley around 40
M
Jup
. We also find a power-law distribution in the host binary fraction beyond 3 au, similar to that found for single stars, indicating no preference of multiplicity for brown dwarfs. Our work also reveals nine substellar systems (GJ 234 B, GJ 494 B, HD 13724 b, HD 182488 b, HD 39060 b and c, HD 4113 C, HD 42581 d, HD 7449 B, and HD 984 b) that have previously been directly imaged, and many others that are observable at existing facilities. Depending on their ages, we estimate that an additional 10–57 substellar objects within our sample can be detected with current imaging facilities, extending the imaged cold (or old) giants by an order of magnitude.
Previous studies suggest genome structure is largely conserved between Eucalyptus species. However, it is unknown if this conservation extends to more divergent eucalypt taxa. We performed ...comparative genomics between the eucalypt genera Eucalyptus and Corymbia. Our results will facilitate transfer of genomic information between these important taxa and provide further insights into the rate of structural change in tree genomes.
We constructed three high density linkage maps for two Corymbia species (Corymbia citriodora subsp. variegata and Corymbia torelliana) which were used to compare genome structure between both species and Eucalyptus grandis. Genome structure was highly conserved between the Corymbia species. However, the comparison of Corymbia and E. grandis suggests large (from 1-13 MB) intra-chromosomal rearrangements have occurred on seven of the 11 chromosomes. Most rearrangements were supported through comparisons of the three independent Corymbia maps to the E. grandis genome sequence, and to other independently constructed Eucalyptus linkage maps.
These are the first large scale chromosomal rearrangements discovered between eucalypts. Nonetheless, in the general context of plants, the genomic structure of the two genera was remarkably conserved; adding to a growing body of evidence that conservation of genome structure is common amongst woody angiosperms.
Context. Exoplanet searches have revealed interesting correlations between the stellar properties and the occurrence rate of planets. In particular, different independent surveys have demonstrated ...that giant planets are preferentially found around metal-rich stars and that their fraction increases with the stellar mass. Aims. During the past six years we have conducted a radial velocity follow-up program of 166 giant stars to detect substellar companions and to characterize their orbital properties. Using this information, we aim to study the role of the stellar evolution in the orbital parameters of the companions and to unveil possible correlations between the stellar properties and the occurrence rate of giant planets. Methods. We took multi-epoch spectra using FEROS and CHIRON for all of our targets, from which we computed precision radial velocities and derived atmospheric and physical parameters. Additionally, velocities computed from UCLES spectra are presented here. By studying the periodic radial velocity signals, we detected the presence of several substellar companions. Results. We present four new planetary systems around the giant stars HIP 8541, HIP 74890, HIP 84056, and HIP 95124. Additionally, we study the correlation between the occurrence rate of giant planets with the stellar mass and metallicity of our targets. We find that giant planets are more frequent around metal-rich stars, reaching a peak in the detection of f = 16.7+15.5-5.9% around stars with Fe/H ~ 0.35 dex. Similarly, we observe a positive correlation of the planet occurrence rate with the stellar mass, between M⋆ ~ 1.0 and 2.1 M⊙, with a maximum of f = 13.0+10.1-4.2% at M⋆ = 2.1 M⊙. Conclusions. We conclude that giant planets are preferentially formed around metal-rich stars. In addition, we conclude that they are more efficiently formed around more massive stars, in the stellar mass range of ~1.0–2.1 M⊙. These observational results confirm previous findings for solar-type and post-MS hosting stars, and provide further support to the core-accretion formation model.
Radial velocity observations from three instruments reveal the presence of a 4 MJup planet candidate orbiting the K giant HD 76920. HD 76920b has an orbital eccentricity of 0.856 0.009, making it the ...most eccentric planet known to orbit an evolved star. There is no indication that HD 76920 has an unseen binary companion, suggesting a scattering event rather than Kozai oscillations as a probable culprit for the observed eccentricity. The candidate planet currently approaches to about four stellar radii from its host star, and is predicted to be engulfed on a ∼100 Myr timescale due to the combined effects of stellar evolution and tidal interactions.
The nuclei below lead but with more than 126 neutrons are crucial to an understanding of the astrophysical r process in producing nuclei heavier than A∼190. Despite their importance, the structure ...and properties of these nuclei remain experimentally untested as they are difficult to produce in nuclear reactions with stable beams. In a first exploration of the shell structure of this region, neutron excitations in ^{207}Hg have been probed using the neutron-adding (d,p) reaction in inverse kinematics. The radioactive beam of ^{206}Hg was delivered to the new ISOLDE Solenoidal Spectrometer at an energy above the Coulomb barrier. The spectroscopy of ^{207}Hg marks a first step in improving our understanding of the relevant structural properties of nuclei involved in a key part of the path of the r process.
We present optical and near-infrared (NIR) photometry of 28 gamma-ray bursts (GRBs) detected by the Swift satellite and rapidly observed by the Reionization and Transients Infrared/Optical (RATIR) ...camera. We compare the optical flux at fiducial times of 5.5 and 11 h after the high-energy trigger to that in the X-ray regime to quantify optical darkness. 46 ± 9 per cent (13/28) of all bursts in our sample and 55 ± 10 per cent (13/26) of long GRBs are optically dark, which is statistically consistently with previous studies. Fitting RATIR optical and NIR spectral energy distributions of 19 GRBs, most (6/7) optically dark GRBs either occur at high redshift (z > 4.5) or have a high dust content in their host galaxies (A
V > 0.3). Performing Kolmogorov–Smirnov tests, we compare the RATIR sample to those previously presented in the literature, finding our distributions of redshift, optical darkness, host dust extinction and X-ray-derived column density to be consistent. The one reported discrepancy is with host galaxy dust content in the BAT6 sample, which appears inconsistent with our sample and other previous literature. Comparing X-ray-derived host galaxy hydrogen column densities to host galaxy dust extinction, we find that GRBs tend to occur in host galaxies with a higher metal-to-dust ratio than our own Galaxy, more akin to the Large and Small Magellanic Clouds. Finally, to mitigate time evolution of optical darkness, we measure βOX, rest at a fixed rest-frame time, t
rest = 1.5 h and fixed rest-frame energies in the X-ray and optical regimes. Choosing to evaluate optical flux at λrest = 0.25 μm, we remove high redshift as a source of optical darkness, demonstrating that optical darkness must result from either high redshift, dust content in the host galaxy along the GRB sight line, or a combination of the two.
Modeling the evolution of composition in a convecting mantle is difficult since the associated chemical diffusivity is very small. Consequently, compositional evolution is often modeled using the ...advection equation which is prone to overdiffusion and spurious oscillations unless special numerical schemes are employed. Similar errors can also occur while modeling the evolution of temperature, since mantle convection is advection dominated. One numerical scheme designed to minimize such errors is the tracer ratio method, in which Lagrangian tracers are used to track each composition in the system in addition to carrying local temperature values that are time dependent. However, tracer spacing may become very uneven during evolution, which can contribute to errors in mass and energy conservation. In this study, a tracer repositioning algorithm designed to promote even tracer coverage is presented and tested using over 400 calculations in a large thermal Rayleigh number/buoyancy ratio parameter space. In particular, the effect of tracer repositioning on mass and energy conservation errors is examined. In most cases, we find that energy errors are roughly an order of magnitude less than mass errors, regardless of tracer repositioning. However, in situations with substantial entrainment of compositionally distinct material, mass errors can be reduced by up to an order of magnitude if tracers are repositioned during model evolution. We also find that for a fixed buoyancy ratio, entrainment of basal material decreases as the thermal Rayleigh number increases.
Key Points
Tracer repositioning strongly reduces mass errors in cases with high compositional entrainment
Energy conservation errors are very small compared to mass errors
Per overturn, for a set buoyancy ratio entrainment decreases with increasing thermal Rayleigh number
Aurorae are detected from all the magnetized planets in our Solar System, including Earth. They are powered by magnetospheric current systems that lead to the precipitation of energetic electrons ...into the high-latitude regions of the upper atmosphere. In the case of the gas-giant planets, these aurorae include highly polarized radio emission at kilohertz and megahertz frequencies produced by the precipitating electrons, as well as continuum and line emission in the infrared, optical, ultraviolet and X-ray parts of the spectrum, associated with the collisional excitation and heating of the hydrogen-dominated atmosphere. Here we report simultaneous radio and optical spectroscopic observations of an object at the end of the stellar main sequence, located right at the boundary between stars and brown dwarfs, from which we have detected radio and optical auroral emissions both powered by magnetospheric currents. Whereas the magnetic activity of stars like our Sun is powered by processes that occur in their lower atmospheres, these aurorae are powered by processes originating much further out in the magnetosphere of the dwarf star that couple energy into the lower atmosphere. The dissipated power is at least four orders of magnitude larger than what is produced in the Jovian magnetosphere, revealing aurorae to be a potentially ubiquitous signature of large-scale magnetospheres that can scale to luminosities far greater than those observed in our Solar System. These magnetospheric current systems may also play a part in powering some of the weather phenomena reported on brown dwarfs.
Purpose
It is becoming increasingly common for researchers to share scientific literature via social media. Traditional bibliometrics have long been utilized to measure a study’s academic impact, but ...they fail to capture the impact generated through social media sharing. Altmetric Attention Score (AAS) is a weighted count of all the online attention garnered by a study, and it is currently unclear whether a relationship with traditional bibliometrics exists.
Methods
We identified the five highest-rated spine-specific and five highest-rated general orthopedic journals by Scopus CiteScore 2020. We then identified all the spine trauma studies across a 5-year span (2016–2020) within these journals and compared AAS with traditional bibliometrics using Independent t-tests and Pearson’s correlational analyses.
Results
No statistically significant relationships were identified between AAS and traditional bibliometrics for articles pertaining to spine trauma: Level of Evidence (
R
= − 0.02,
p
= 0.34), H-Index Primary Author (
R
= < − 0.01,
p
= 0.50), H-Index Senior Author (
R
= − 0.04,
p
= 0.24), and Number of Citations (
R
= 0.01,
p
= 0.40). The top five articles by AAS include those pertaining to motorcycle injuries (AAS = 687), orthosis in thoracolumbar fractures (AAS = 199), golfing injuries (AAS = 166), smartphone-based teleradiology (AAS = 41), and auto racing injuries (AAS = 39).
Conclusion
The lack of overlap between these types of metrics suggests that AAS or similar alternative metrics should be used to measure an article’s social impact. The social impact of an article should likewise be a factor in determining an article’s overall impact along with its academic impact as measured by bibliometrics.
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