Formation of Power-law Energy Spectra in Space Plasmas by Stochastic Acceleration due to Whistler-Mode Waves

A non-relativistic Fokker-Planck equation for the electron distribution function is formulated incorporating the effects of stochastic acceleration by whistler-mode waves and Coulomb collisions. The stationary solution $f$ to the equation, subject to a zero-flux boundary condition, is found to be a generalized Lorentzian (or kappa) distribution, which satisfies $f\propto v^{-2(\kappa+1)}$ for large velocity $v$, where $\kappa$ is the spectral index. The parameter $\kappa$ depends strongly on the relative wave intensity $R$. Taking into account the critical energy required for resonance of electrons with whistlers, we calculate a range of values of $R$ for each of a number of different space plasmas for which kappa distributions can be expected to be formed. This study is one of the first in the literature to provide a theoretical justification for the formation of generalized Lorentzian (or kappa) particle distribution functions in space plasmas.Comment: 14 page-Latex, 1 ps-figure, agums.st

Rapid acceleration of electrons in the magnetosphere by fast-mode MHD waves

During major megnetic storms, enhanced flux of relativistic electrons in the inner magnetosphere have been observed to correleated with ULF waves. The enhancements can take place over a period of several hours. In order to account for such a rapid generation of relativistic electrons, we examine the mechanism of transit-time acceleration of electrons by low-frequency fast-mode MHD waves, here the assumed form of ULF waves. Calcaulations of the acceleration timescales in the model show that fast-mode waves in the Pc4 to Pc5 frequency range, with typically observed wave amplitudes 10--20 nT, can accelerate the seed electrons to energies of order MeV in a period of a few hours.Comment: 9 pages, 3 figures, Accepted to J. Geophys. Re

Particle Simulation of the Generation of Plasmaspheric Hiss

We have conducted a one‐dimensional electromagnetic particle simulation with a parabolic magnetic field to reproduce whistler‐mode hiss emissions in the plasmasphere. We assume a bi‐Maxwellian distribution with temperature anisotropy for energetic electrons injected into the plasmasphere and find that hiss emissions are generated with spectrum characteristics typical of those observed by spacecraft near the magnetic equator. The hiss emissions contain fine structures involving rising tone and falling tone elements with variation in frequencies. The amplitude profile of the spectra agrees with the optimum wave amplitude derived from the nonlinear wave growth theory. The simulation demonstrates that hiss emissions are generated locally near the magnetic equator through linear and nonlinear interactions with energetic electrons with temperature anisotropy. The coherent hiss emissions efficiently scatter resonant electrons of 2.5–80 keV into the loss cone

GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19

Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte-macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A)

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical Covid-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalisation2-4 following SARS-CoV-2 infection. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from critically-ill cases with population controls in order to find underlying disease mechanisms. Here, we use whole genome sequencing in 7,491 critically-ill cases compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical Covid-19. We identify 16 new independent associations, including variants within genes involved in interferon signalling (IL10RB, PLSCR1), leucocyte differentiation (BCL11A), and blood type antigen secretor status (FUT2). Using transcriptome-wide association and colocalisation to infer the effect of gene expression on disease severity, we find evidence implicating multiple genes, including reduced expression of a membrane flippase (ATP11A), and increased mucin expression (MUC1), in critical disease. Mendelian randomisation provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5, CD209) and coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of Covid-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication, or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between critically-ill cases and population controls is highly efficient for detection of therapeutically-relevant mechanisms of disease

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care(1) or hospitalization(2-4) after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease. © 2022, The Author(s)