Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Feeding of Raw Meat Diets to Dogs: Principles and Practice in the UK

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Atom Probe Tomography Study of Multi-Microalloyed Carbide and Carbo-Nitride Precipitates and the Precipitation Sequence in Nb-Ti HSLA Steels

Composition analysis of carbide and carbo-nitride precipitates was performed for two Nb-Ti microalloyed steels with yield strengths of 750 and 580 MPa using an atom probe study. In the high-Ti 750 MPa steel, Ti-rich (Ti,Nb)(C,N) and Ti-rich (Ti,Nb)(C) precipitates were observed. In the high-Nb 580 MPa steel, a Ti-rich (Ti,Nb)(C,N) precipitate and (Ti,Nb)(C) clusters were noted. These (Ti,Nb)(C) clusters in the high-Nb 580 MPa steel were smaller than the (Ti,Nb)(C) precipitates in high-Ti 750 MPa steel. In general, a larger number of precipitates were found in the high-Ti 750 MPa steel. This difference in the number density of the precipitates between the two steels is attributed to the difference in Ti content. Combining the atom probe tomography results and thermodynamic calculations, the precipitation sequence in these alloys was inferred to be the following: as the temperature decreases, TiN precipitates out of the solution with successive (Ti,Nb)(C,N) layers of varying composition forming on these Ti-rich precipitates. Once N is depleted from the solution, a second set of (Ti,Nb)(C) precipitates in a similar manner in the matrix and also onto the carbo-nitride phase. This observation is consistent with previous observations in high-strength low-alloy steels containing comparable amounts of only Nb. It was noted that the amount of Nb, Nb/(Nb + Ti), in the precipitates decreased from 0.20 to 0.04 with the size of the precipitate. We believe that this is due to the Nb supersaturation in the matrix when these precipitates nucleate