F-GAMMA: On the phenomenological classification of continuum radio spectra variability patterns of Fermi blazars

The F-GAMMA program is a coordinated effort to investigate the physics of Active Galactic Nuclei (AGNs) via multi-frequency monitoring of Fermi blazars. In the current study we show and discuss the evolution of broad-band radio spectra, which are measured at ten frequencies between 2.64 and 142 GHz using the Effelsberg 100-m and the IRAM 30-m telescopes. It is shown that any of the 78 sources studied can be classified in terms of their variability characteristics in merely 5 types of variability. It is argued that these can be attributed to only two classes of variability mechanisms. The first four types are dominated by spectral evolution and can be described by a simple two-component system composed of: (a) a steep quiescent spectral component from a large scale jet and (b) a time evolving flare component following the "Shock-in-Jet" evolutionary path. The fifth type is characterised by an achromatic change of the broad band spectrum, which could be attributed to a different mechanism, likely involving differential Doppler boosting caused by geometrical effects. Here we present the classification, the assumed physical scenario and the results of calculations that have been performed for the spectral evolution of flares.Comment: Proceedings of the conference: "The Central Kiloparsec in Galactic Nucleic: Astronomy at High Angular Resolution 2011", August 29 - September 2, 2011, Bad Honnef, German

Catching the radio flare in CTA 102. II. VLBI kinematic analysis

Context. Very Long Baseline Interferometry (VLBI) observations can resolve the radio structure of Active Galactic Nuclei (AGN) and provide estimates of the structural and kinematic characteristics at parsec-scales in their jets. The changes in the kinematics of the observed jet features can be used to study the physical conditions in the innermost regions of these sources. We performed multi-frequency multi-epoch Very Long Baseline Array (VLBA) observations of the blazar CTA102 during its 2006 radio flare, the strongest ever reported for this source. These observations provide an excellent opportunity to investigate the evolution of the physical properties of blazars, especially during these flaring events Aims. We want to study the kinematic changes in the source during the strong radio outburst in April 2006 and test the assumption of a shock-shock interaction. This assumption is based on the analysis and modeling of the single dish observations of CTA102 (Paper I). Methods. In this paper we study the kinematics of CTA102 at several frequencies using VLBI observations. From the modeled jet features we derive estimates on the evolution of the physical parameters, such as the particle density and the magnetic field. Furthermore, we combine our observations during the 2006 flare with long-term VLBA monitoring of the source at 15 GHz and 43 GHz. Results. We cross-identified seven features throughout our entire multifrequency observations and find evidence of two possible recollimation shocks around 0.1   mas (deprojected 18 pc at a viewing angle ϑ = 2.6°) and 6.0   mas (deprojected 1 kpc) from the core. The 43   GHz observations reveal a feature ejected at epoch tej = 2005.9 ± 0.2, which could be connected to the 2006 April radio flare. Furthermore, this feature might be associated with the traveling component involved in the possible shock-shock interaction, which gives rise to the observed double peak structure in the single-dish light curves reported in Paper I

TANAMI monitoring of Centaurus A: The complex dynamics in the inner parsec of an extragalactic jet

Context. Centaurus A (Cen A) is the closest radio-loud active galactic nucleus. Very Long Baseline Interferometry (VLBI) enables us to study the spectral and kinematic behavior of the radio jet¿counterjet system on milliarcsecond scales, providing essential information for jet emission and propagation models. Aims. In the framework of the TANAMI monitoring, we investigate the kinematics and complex structure of Cen A on subparsec scales. We have been studying the evolution of the central parsec jet structure of Cen A for over 3.5 years. The proper motion analysis of individual jet components allows us to constrain jet formation and propagation and to test the proposed correlation of increased high-energy flux with jet ejection events. Cen A is an exceptional laboratory for such a detailed study because its proximity translates to unrivaled linear resolution, where one milliarcsecond corresponds to 0.018 pc. Methods. As a target of the southern-hemisphere VLBI monitoring program TANAMI, observations of Cen A are done approximately every six months at 8.4 GHz with the Australian Long Baseline Array (LBA) and associated telescopes in Antarctica, Chile, New Zealand, and South Africa, complemented by quasi-simultaneous 22.3 GHz observations. Results. The first seven epochs of high-resolution TANAMI VLBI observations at 8.4 GHz of Cen A are presented, resolving the jet on (sub-)milliarcsecond scales. They show a differential motion of the subparsec scale jet with significantly higher component speeds farther downstream where the jet becomes optically thin. We determined apparent component speeds within a range of 0.1c to 0.3c and identified long-term stable features. In combination with the jet-to-counterjet ratio, we can constrain the angle to the line of sight to theta approx 12deg-45deg. Conclusions. The high-resolution kinematics are best explained by a spine-sheath structure supported by the downstream acceleration occurring where the jet becomes optically thin. On top of the underlying, continuous flow, TANAMI observations clearly resolve individual jet features. The flow appears to be interrupted by an obstacle causing a local decrease in surface brightness and circumfluent jet behavior. We propose a jet-star interaction scenario to explain this appearance. The comparison of jet ejection times to high X-ray flux phases yields a partial overlap of the onset of the X-ray emission and increasing jet activity, but the limited data do not support a robust correlation

Future mmVLBI Research with ALMA: a European vision

Very long baseline interferometry at millimetre/submillimetre wavelengths (mmVLBI) offers the highest achievable spatial resolution at any wavelength in astronomy. The anticipated inclusion of ALMA as a phased array into a global VLBI network will bring unprecedented sensitivity and a transformational leap in capabilities for mmVLBI. Building on years of pioneering efforts in the US and Europe the ongoing ALMA Phasing Project (APP), a US-led international collaboration with MPIfR-led European contributions, is expected to deliver a beamformer and VLBI capability to ALMA by the end of 2014 (APP: Fish et al. 2013, arXiv:1309.3519). This report focuses on the future use of mmVLBI by the international users community from a European viewpoint. Firstly, it highlights the intense science interest in Europe in future mmVLBI observations as compiled from the responses to a general call to the European community for future research projects. A wide range of research is presented that includes, amongst others: - Imaging the event horizon of the black hole at the centre of the Galaxy - Testing the theory of General Relativity an/or searching for alternative theories - Studying the origin of AGN jets and jet formation - Cosmological evolution of galaxies and BHs, AGN feedback - Masers in the Milky Way (in stars and star-forming regions) - Extragalactic emission lines and astro-chemistry - Redshifted absorption lines in distant galaxies and study of the ISM and circumnuclear gas - Pulsars, neutron stars, X-ray binaries - Testing cosmology - Testing fundamental physical constant

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

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

Data availability: Downloadable summary data are available through the GenOMICC data site (https://genomicc.org/data). Summary statistics are available, but without the 23andMe summary statistics, except for the 10,000 most significant hits, for which full summary statistics are available. The full GWAS summary statistics for the 23andMe discovery dataset will be made available through 23andMe to qualified researchers under an agreement with 23andMe that protects the privacy of the 23andMe participants. For further information and to apply for access to the data, see the 23andMe website (https://research.23andMe.com/dataset-access/). All individual-level genotype and whole-genome sequencing data (for both academic and commercial uses) can be accessed through the UKRI/HDR UK Outbreak Data Analysis Platform (https://odap.ac.uk). A restricted dataset for a subset of GenOMICC participants is also available through the Genomics England data service. Monocyte RNA-seq data are available under the title ‘Monocyte gene expression data’ within the Oxford University Research Archives (https://doi.org/10.5287/ora-ko7q2nq66). Sequencing data will be made freely available to organizations and researchers to conduct research in accordance with the UK Policy Framework for Health and Social Care Research through a data access agreement. Sequencing data have been deposited at the European Genome–Phenome Archive (EGA), which is hosted by the EBI and the CRG, under accession number EGAS00001007111.Extended data figures and tables are available online at https://www.nature.com/articles/s41586-023-06034-3#Sec21 .Supplementary information is available online at https://www.nature.com/articles/s41586-023-06034-3#Sec22 .Code availability: Code to calculate the imputation of P values on the basis of SNPs in linkage disequilibrium is available at GitHub (https://github.com/baillielab/GenOMICC_GWAS).Acknowledgements: We thank the members of the Banco Nacional de ADN and the GRA@CE cohort group; and the research participants and employees of 23andMe for making this work possible. A full list of contributors who have provided data that were collated in the HGI project, including previous iterations, is available online (https://www.covid19hg.org/acknowledgements).Change history: 11 July 2023: A Correction to this paper has been published at: https://doi.org/10.1038/s41586-023-06383-z. -- In the version of this article initially published, the name of Ana Margarita Baldión-Elorza, of the SCOURGE Consortium, appeared incorrectly (as Ana María Baldion) and has now been amended in the HTML and PDF versions of the article.Copyright © The Author(s) 2023, 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).GenOMICC was funded by Sepsis Research (the Fiona Elizabeth Agnew Trust), the Intensive Care Society, a Wellcome Trust Senior Research Fellowship (to J.K.B., 223164/Z/21/Z), the Department of Health and Social Care (DHSC), Illumina, LifeArc, the Medical Research Council, UKRI, a BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070 and BBS/E/D/30002275) and UKRI grants MC_PC_20004, MC_PC_19025, MC_PC_1905 and MRNO2995X/1. A.D.B. acknowledges funding from the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z), the Edinburgh Clinical Academic Track (ECAT) programme. This research is supported in part by the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant MC_PC_20029). Laboratory work was funded by a Wellcome Intermediate Clinical Fellowship to B.F. (201488/Z/16/Z). We acknowledge the staff at NHS Digital, Public Health England and the Intensive Care National Audit and Research Centre who provided clinical data on the participants; and the National Institute for Healthcare Research Clinical Research Network (NIHR CRN) and the Chief Scientist’s Office (Scotland), who facilitate recruitment into research studies in NHS hospitals, and to the global ISARIC and InFACT consortia. GenOMICC genotype controls were obtained using UK Biobank Resource under project 788 funded by Roslin Institute Strategic Programme Grants from the BBSRC (BBS/E/D/10002070 and BBS/E/D/30002275) and Health Data Research UK (HDR-9004 and HDR-9003). UK Biobank data were used in the GSMR analyses presented here under project 66982. The UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government, British Heart Foundation and Diabetes UK. The work of L.K. was supported by an RCUK Innovation Fellowship from the National Productivity Investment Fund (MR/R026408/1). J.Y. is supported by the Westlake Education Foundation. SCOURGE is funded by the Instituto de Salud Carlos III (COV20_00622 to A.C., PI20/00876 to C.F.), European Union (ERDF) ‘A way of making Europe’, Fundación Amancio Ortega, Banco de Santander (to A.C.), Cabildo Insular de Tenerife (CGIEU0000219140 ‘Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19’ to C.F.) and Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC20/57 to C.F.). We also acknowledge the contribution of the Centro National de Genotipado (CEGEN) and Centro de Supercomputación de Galicia (CESGA) for funding this project by providing supercomputing infrastructures. A.D.L. is a recipient of fellowships from the National Council for Scientific and Technological Development (CNPq)-Brazil (309173/2019-1 and 201527/2020-0)