Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

Multiplicity Distributions in νμp Interactions

Multiplicity distributions of the hadrons produced in antineutrino proton interactions are presented. The data sample, which consists of 2025 charged-current events with antineutrino energy greater than 5 GeV, comes from exposures of the 15-foot hydrogen bubble chamber to the broad-band antineutrino beam at Fermilab. The distribution in hadronic mass W has an average value of 3.7 GeV but extends up to 10 GeV. The mean multiplicity of charged hadrons depends on the hadronic mass W and varies as = (-0.44 +- 0.13) + (1.48 +- 0.06) 1n W/sup 2/ for W/sup 2/ > 4 GeV/sup 2/. The mean multiplicities for events with three or more charged tracks averaged over the total data sample are = 1.68 +-0.03 and = 1.11 +- 0.07 for ..pi../sup -/ and ..pi../sup 0/ production, respectively. The mean ..pi../sup 0/ multiplicity is found to increase slowly with n/sub -/. The integrated correlation coefficient f/sub 2//sup - -/ and the dispersion D/sup -/ are given as a function of n/sub -/. When compared to the distributions characteristic of other leptonic and hadronic reactions, a similarity is found between the anti ..nu..- data and results from hadronic reactions that have no diffractive component. Multiplicity data for the heavier particles K/sup 0/, rho and ..lambda.. are also summarized. The pion multiplicities in the current fragmentation region exceed those for the target fragmentation at all W values. They also satisfy the isospin relation 2 = + required for the fragmentation of an I = 1/2 quark when a W > 4 GeV selection is imposed

SABRINA the Italian Mission for Endowing COSMO-SkyMed with Bistatic and Interferometric Capabilities

This paper focuses main characteristics and expected performance of SABRINA (System for Advanced Bistatic and Radar INterferometric Applications) Mission which has been selected by the Italian Space Agency for complementing COSMO-SkyMed, the Italian constellation for high spatial and temporal resolution SAR imaging of the Earth. After a brief presentation of COSMO-SkyMed development status, the key aspects of the mission and expected applications and products are dealt in detail

Location of abnormal parathyroid glands: lessons from 810 parathyroidectomies

Primary hyperparathyroidism (pHPT) is commonly treated with targeted parathyroidectomy (PTX) guided by preoperative imaging and intraoperative parathormone monitoring. Despite advanced imaging techniques, failure of parathyroid localization still occurs. This study determines the anatomical distribution of single abnormal parathyroid glands, which may help direct the surgeon in PTX when preoperative localization is unsuccessful. A retrospective review of prospectively collected data of 810 patients with pHPT who underwent initial PTX at a tertiary medical center was performed. All patients had biochemically confirmed pHPT and single-gland disease. Abnormal parathyroid gland localization was determined at time of operation, correlated with operative and pathology reports, and confirmed by operative success defined as eucalcemia for ≥6 mo after PTX. Patients with multiple endocrine neoplasia, secondary, tertiary, or familial hyperparathyroidism, multiglandular disease, parathyroid cancer, and ectopic glands were excluded. Data were analyzed by chi-square and Z-test analyses. Among 810 patients who underwent PTX for pHPT, single abnormal parathyroid glands were unequally distributed among the four eutopic locations (left superior, 15.7%; left inferior, 31.3%; right superior, 15.8%; right inferior, 37.2%; P < 0.01). Abnormal inferior parathyroid glands (68.5%) were significantly more common than abnormal superior glands (31.5%), respectively (P < 0.01). In men, the most common location for single abnormal parathyroid glands was the right inferior position (43.4%, P < 0.01). Overall, there was no significant difference in laterality. This large series of patients suggests that single eutopic abnormal parathyroid glands are more likely to be inferior. In men, moreover, if an abnormal parathyroid gland is not localized preoperatively, the right inferior location should be explored first. Nevertheless, successful PTX remains predicated on knowledge of parathyroid anatomy, experience, and judgment of the surgeon

Characterization of nebulization generated aerosol particles dispersion and deposition by total reflection X-ray fluorescence

To prevent air pollution and achieve air quality regulations, it is essential to develop analytical techniques that can determine the concentration of metals in aerosol particles, both in the gas phase and after collection onto filters. Total reflection X-ray fluorescence spectroscopy (TXRF) and laser-induced breakdown spectroscopy (LIBS) are emerging as complementary techniques for determining the elemental composition of aerosol particles. The accuracy of their results relies on calibration methods based on aerosol and multi-element filters representative of the on-line measurement conditions and particulate collection for off-line measurement, respectively. In this paper we propose a novel methodology for characterizing nebulization generated aerosol particles dispersion and deposition by means of TXRF to assess the use of an aerosol generator to produce calibration samples for LIBS and TXRF analysis. Particles concentration and size distribution of the aerosol produced by nebulizing a Cu salt aqueous solution are measured inside a glove box modifying the production parameters and collecting the corresponding particulate deposited on reflectors. The most stable conditions are observed at average flow rate and selected for studying the aerosol spatial distribution. The Cu mass collected on reflectors positioned at a fixed distance and radial geometry with respect to the nozzle exit is measured by TXRF and increases linearly with time. Results suggest that this experimental configuration could be used to realize calibration samples for TXRF analysis representative of particulate deposition. The use of these aerosols as LIBS calibration samples could lead to significant errors due to the observed flow asymmetry.Copyright (c) 2022 American Association for Aerosol Researc

The PRISMA imaging spectroscopy mission: overview and first performance analysis

The PRISMA satellite mission launched on March 22nd, 2019 is one of the latest spaceborne imaging spectroscopy mission for Earth Observation. The PRISMA satellite comprises a high-spectral resolution VNIR-SWIR imaging spectrometer and a panchromatic camera. In summer 2019, first operations during the commissioning phase were mainly devoted to acquisitions in specific areas for evaluating instrument functioning, in-flight performance, and mission data product accuracy. A field and airborne campaign was carried out over an agriculture area in Italy to collect in-situ multi-source spectroscopy measurements at different scales simultaneously with PRISMA. The spectral, radiometric and spatial performance of PRISMA Level 1 Top-Of-Atmosphere radiance (LTOA) product were analyzed. The in-situ surface reflectance measurements over different landcovers were propagated to LTOA using MODTRAN5 radiative transfer simulations and compared with satellite observations. Overall, this work offers a first quantitative evaluation about the PRISMA mission performance and imaging spectroscopy LTOA data product consistency. Our results show that the spectral smile is less than 5 nm, the average spectral resolution is 13 nm and 11 nm (VNIR and SWIR respectively) and it varies ±2 nm across track. The radiometric comparison between PRISMA and field/airborne spectroscopy shows a difference lower than 5% for NIR and SWIR, whereas it is included in the 2–7% range in the VIS. The estimated instrument signal to noise ratio (SNR) is ≈400–500 in the NIR and part of the SWIR (1600 nm). The VNIR-to-SWIR spatial co-registration error is below 8 m and the spatial resolution is 37.11 m and 38.38 m for VNIR and SWIR respectively. The results are in-line with the expectations and mission requirements and indicate that acquired images are suitable for further scientific applications. However, this first assessment is based on data from a rural area and this cannot be fully exhaustive. Further studies are needed to confirm the performance for other land cover types like snow, inland and coastal waters, deserts or urban areas