A tool for translating polygenic scores onto the absolute scale using summary statistics

There is growing interest in the clinical application of polygenic scores as their predictive utility increases for a range of health-related phenotypes. However, providing polygenic score predictions on the absolute scale is an important step for their safe interpretation. We have developed a method to convert polygenic scores to the absolute scale for binary and normally distributed phenotypes. This method uses summary statistics, requiring only the area-under-the-ROC curve (AUC) or variance explained (R2) by the polygenic score, and the prevalence of binary phenotypes, or mean and standard deviation of normally distributed phenotypes. Polygenic scores are converted using normal distribution theory. We also evaluate methods for estimating polygenic score AUC/R2 from genome-wide association study (GWAS) summary statistics alone. We validate the absolute risk conversion and AUC/R2 estimation using data for eight binary and three continuous phenotypes in the UK Biobank sample. When the AUC/R2 of the polygenic score is known, the observed and estimated absolute values were highly concordant. Estimates of AUC/R2 from the lassosum pseudovalidation method were most similar to the observed AUC/R2 values, though estimated values deviated substantially from the observed for autoimmune disorders. This study enables accurate interpretation of polygenic scores using only summary statistics, providing a useful tool for educational and clinical purposes. Furthermore, we have created interactive webtools implementing the conversion to the absolute (https://opain.github.io/GenoPred/PRS_to_Abs_tool.html). Several further barriers must be addressed before clinical implementation of polygenic scores, such as ensuring target individuals are well represented by the GWAS sample.

On Variable Speed of Light and Relativity of Constantaneity

An axiomatic theory is proposed that reconciles the existence of an absolute scale for time (Planck time) and special relativity. According to this theory speed of light c becomes a variable which is proposed to be taken as the fifth dimension.

A Tool for Translating Polygenic Scores onto the Absolute Scale Using Summary Statistics

Background: There is growing interest in the clinical application of polygenic scores as their predictive utility increases for a range of health-related phenotypes. However, providing polygenic score predictions on the absolute scale is an important step for their safe interpretation. Currently, polygenic scores can only be converted to the absolute scale when a validation sample is available, presenting a major limitation in the interpretability and clinical utility of polygenic scores. Methods: We have developed a method to convert polygenic scores to the absolute scale for binary and normally distributed phenotypes. This method uses summary statistics, requiring only the area-under-the-ROC curve (AUC) or variance explained (R2) by the polygenic score, and the prevalence of binary phenotypes, or mean and standard deviation of normally distributed phenotypes. Polygenic scores are converted using normal distribution theory. Given the AUC/R2 of polygenic scores may be unknown, we also evaluate two methods (AVENGEME, lassosum) for estimating these values from genome-wide association study (GWAS) summary statistics alone. We validate the absolute risk conversion and AUC/R2 estimation using data for eight binary and three continuous phenotypes in the UK Biobank sample. Results: When the AUC/R2 of the polygenic score is known, the observed and estimated absolute values were highly concordant. Across binary phenotypes, the mean absolute difference between the observed and estimated proportion of cases was 5%. For continuous phenotypes, the mean absolute difference between observed and estimated means was <0.3%. Estimates of AUC/R2 from the lassosum pseudovalidation method were most similar to the observed AUC/R2 values, though estimated values deviated substantially from the observed for autoimmune disorders. Conclusion: This study enables accurate interpretation of polygenic scores using only summary statistics, providing a useful tool for educational and clinical purposes. Furthermore, we have created interactive webtools implementing the conversion to the absolute scale for binary and normally distributed phenotypes (https://opain.github.io/GenoPred/PRS_to_Abs_tool.html). Several further barriers must be addressed before clinical implementation of polygenic scores, such as ensuring target individuals are well represented by the GWAS sample.

Quantitative electronic structure and work-function changes of liquid water induced by solute

Recent advancement in quantitative liquid-jet photoelectron spectroscopy enables the accurate determination of the absolute-scale electronic energetics of liquids and species in solution. The major objective of the present work is...

Fusion Key Frame Image Confidence Assessment of the Medical Service Robot Whole Scene Reconstruction

Facing the precise service and emergency rescue needs of medical service robots in irregular scene, in order to achieve better navigation and path planning for robots in service scenarios, for the whole reconstruction of the absolute scale service scenario, this article proposes a frame of whole scene three-dimensional (3D) point cloud reconstruction based on the fusion of scene depth estimation, confidence assessment, and pose tracking with monocular camera. The algorithm first collects the scene focus stack images under an initial viewing angle through the robot mobile terminal of camera. The absolute depth information of the scene is estimated on the server side, and the confidence level of the reconstructed image of the point cloud is evaluated, and non- uniform sampling is performed to reduce the influence of the error estimation. Based on the sparse key frame position information defined by monocular SLAM, the 3D reconstruction of the whole scene in absolute scale is realized through multi-perspective point cloud pose matching. It provides information of cloud reconstruction of scenic spots for target recognition and navigation of a medical service robot.

Photon leaking or very hard ionizing radiation? Unveiling the nature of He II-emitters using the softness diagram

Aims. Star-forming galaxies with nebular He II emission contain very energetic ionizing sources of radiation, which can be considered as analogs to the major contributors of the reionization of the Universe in early epochs. It is therefore of great importance to provide a reliable absolute scale for the equivalent effective temperature (T*) for these sources. Methods. We study a sample of local (z < 0.2) star-forming galaxies showing optical nebular He II emission using the so-called softness diagrams, involving emission lines of two elements in two consecutive stages of ionization (e.g., [S II]/[S III] vs. [O II]/[O III]). We use for the first time the He I/He II ratio in these diagrams in order to explore the higher range of T* expected in these objects, and to investigate the role of possible mechanisms driving the distribution of galaxy points in these diagrams. We build grids of photoionization models covering different black-body temperatures, model cluster atmospheres, and density-bounded geometries to explain the conditions observed in the sample. Results. We verified that the use of the softness diagrams including the emission-line ratio He I/He II combined with black-body photoionization models can provide an absolute scale of T* for these objects. The application of a Bayesian-like code indicates T* in the range 50−80 kK for the sample of galaxies, with a mean value higher than 60 kK. The average of these high temperature values can only be reproduced using cluster model populations with nearly metal-free stars, although such ionizing sources cannot explain either the highest T* values, beyond 1σ, or the dispersion observed in the softness diagrams. According to our photoionization models, most sample galaxies could be affected to some extent by ionizing photon leaking, presenting a mean photon absorption fraction of 26% or higher depending on the metallicity assumed for the ionizing cluster. The entire range of He I/He II, [S II]/[S III], and [O II]/[O III] ratios for these HeII-emitting galaxies is reproduced with our models, combining nearly metal-free ionizing clusters and photon leaking under different density-bounded conditions.

Extending the Global Space-Based Inter-Calibration System (GSICS) to Tie Satellite Radiances to an Absolute Scale

The Global Space-based Inter-Calibration System (GSICS) routinely monitors the calibration of various channels of Earth-observing satellite instruments and generates GSICS Corrections, which are functions that can be applied to tie them to reference instruments. For the infrared channels of geostationary imagers GSICS algorithms are based on comparisons of collocated observations with hyperspectral reference instruments; whereas Pseudo Invariant Calibration Targets are currently used to compare the counterpart channels in the reflected solar band to multispectral reference sensors. This paper discusses how GSICS products derived from both approaches can be tied to an absolute scale using specialized satellite reference instruments with SI-traceable calibration on orbit. This would provide resilience against gaps between reference instruments and drifts in their calibration outside their overlap period and allow construction of robust and harmonized data records from multiple satellite sources to build Fundamental Climate Data Records, as well as more uniform environmental retrievals in both space and time, thus improving inter-operability.

Analysis of Scale Factors on China’s Sustainable Development Efficiency Based on Three-Stage DEA and a Double Threshold Test

Based on the Driver-Pressure-State-Impact-Response (DPSIR) framework, this paper constructs the input, expected output, and unexpected output of China’s sustainable development. This paper calculates the sustainable development efficiency of 31 provinces and cities in China using a super-slack-based measure (SBM) model that eliminates the influence of scale factors through a three-stage data envelope analysis (DEA) approach. Taking the level of science and technology as the control variable, and the relative scale efficiency as the threshold variable, this paper calculates the effects of the absolute scale of labor force, education, economy, enterprise, and transportation on sustainable development efficiency. The results show that: (1) there is an upward trajectory for sustainable development efficiency of China’s provinces and municipalities overall from 0.65 in 2004 to 0.68 in 2017, with significant regional differences in which the ecological efficiency in the Eastern region is 0.26 higher than that of the Central region; (2) it enhances the absolute scale of the labor force, education, and transportation, in order to reduce the inhibition on sustainable development efficiency; and (3) shifts our attention to the promotion of absolute economic scale to the promotion of green economic development, and increases control of polluting enterprises.