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

Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference

The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique\u2014Subtype and Stage Inference (SuStaIn)\u2014able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer\u2019s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype (p = 7.18 7 10 124 ) or temporal stage (p = 3.96 7 10 125 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine

Active axial eye motion tracking by extended range, closed loop OPDlocked white light interferometer for combined confocal/ en face optical coherence tomography imaging of the human eye fundus in vivo

We report an active tracking device based on white light coherence ranging using a spectrally interrogated Michelson interferometer, which is used to monitor and correct for the axial displacement of the eye and head of the subject in a confocal scanning ophthalmoscope/ en face OCT system (SLO/OCT). The Nyquist limit range of the spectrometer in the tracking interferometer is ~5.4 mm, which is adequate for monitoring the axial position of axially extended layered objects like the human eye fundus. Both the tracking and imaging interferometers share the eye interface optics and the sample and also an optical path (OPD) changing device in the reference (fast voice coil mounted retroreflector), that keeps them locked at constant OPD values. As a consequence, the sensitivity of the tracking interferometer is not affected by the spectrometer sensitivity roll-off with increased OPD and mirror term ambiguity tracking errors close to OPD = 0 are eliminated. Moreover, the axial tracking range is only limited by the voice coil stage travel range. A real time data acquisition processor board is used to digitize the spectrometer signal and calculate the correction signal applied to the voice coil with an update time better than 5 ms. We demonstrate axial motion corrected combined confocal/ en face OCT imaging of the human eye fundus in vivo

Effect of information formats on information services: analysis of four selected agricultural commodities in the USA

We analyze sources of information in agricultural markets to understand patterns of demand for decision support services and the division of labor in the supply of these services. Information formatting-qualitative variation that determines accessibility and relevance of information in specific contexts-prohibits universal access to informational content. Information formats give rise to both transaction costs and complementarities reflected in patterns of information exchange in commodity systems. Controlling for actors' structural roles and levels of education, we develop a hedonic model of information demand such that actors seek information that is formatted to meet their needs and capabilities. Employing survey data, we explain elements of observed patterns of information exchange in four commodity systems in the USA. Results point to opportunities to expand our understanding of socioeconomic processes underlying production and consumption of decision support. Copyright 2006 International Association of Agricultural Economists.

Mortality Risk and the Value of a Statistical Life: The Dead-Anyway Effect Revis(it)ed

In the expected-utility theory of the monetary value of a statistical life, a well-known result found by Pratt and Zeckhauser [1996] asserts that an individuals’ willingness to pay (WTP) for a marginal reduction in mortality risk increases with the initial level of risk. Their reasoning is based on the so-called “dead-anyway effect” which states that marginal utility of a dollar in the state of death is smaller than in the state of survival. However, this explanation is based on the absence of markets for contingent claims, i.e. annuities and life insurance. This paper reexamines the relationship between WTP and the level of risk under more general circumstances and establishes two main results: first, when insurance markets are perfect, for a risk-averse individual without a bequest motive, marginal WTP for survival does increase with the level of risk but this occurs for a different reason, namely an income effect. Secondly, when the individual has a bequest motive and is endowed with a sufficient amount of wealth from human capital, the effect of initial risk on WTP for survival is reversed: the higher initial risk the lower the value of a statistical life. In the imperfect-markets case we interpret this result as a “constrained-bequest effect”. Copyright The Geneva Association 2005value of life, expected utility, willingness to pay, insurance markets,