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 hospitalization2,3,4 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

System for control of electroslag casting in a collar mold

This report describes the initial development of an electroslag casting control system. The main emphasis of our work and the results reported herein deal with the attempts to develop techniques for locating and controlling the liquid slag-metal interface. Thermocouples embedded in the mold wall provide a simple but accurate means for locating the interface

Computer-operated quartz differential dilatometer

From international symposium on thermal expansion of solids; Lake of the Czarks, Missouri, USA (7 Nov 1973). A quartz differential dilatometer was interfaced with a Digital Equipment Corporation PDP-8 computer to automatically measure the thermal expansion of solids from 300 to 1000 K. A Carson-Dice Electronic-Mechanicai Micrometer, readable to 2.5 x 10/sup -6/ cm, was employed for length-change measurements accurate to 2.5 x 10/sup -5/ cm. Calibrated Pt/Pt/ sub 90/Rh/sub 10/ thermocouples were used to measure temperature changes to plus or minus 0.22 K. The software and hardware necessary to completely automate the measurements are described. Measurements on National Bureau of Standards certified quartz, tungsten, and copper specimens demonstrated an accuracy of plus or minus 1.5% in determination of the coefficient of thermal expansion. (auth

A semiautomated computer-interactive dynamic impact testing system

A computer-assisted semiautomated system has been developed for testing a variety of specimen types under dynamic impact conditions. The primary use of this system is for the testing of Charpy specimens. Full-, half-, and third-size specimens have been tested, both in the lab and remotely in a hot cell for irradiated specimens. Specimens are loaded into a transfer device which moves the specimen into a chamber, where a hot air gun is used to heat the specimen, or cold nitrogen gas is used for cooling, as required. The specimen is then quickly transferred from the furnace to the anvils and then broken. This system incorporates an instrumented tup to determine the change in voltage during the fracture process. These data are analyzed by the computer system after the test is complete. The voltage-time trace is recorded with a digital oscilloscope, transferred to the computer, and analyzed. The analysis program incorporates several unique features. It interacts with the operator and identifies the maximum voltage during the test, the amount of rapid fracture during the test (if any), and the end of the fracture process. The program then calculates the area to maximum voltage and the total area under the voltage-time curve. The data acquisition and analysis part of the system can also be used to conduct other dynamic testing. Dynamic tear and precracked specimens can be tested with an instrumented tup and analyzed in a similar manner. 3 refs., 7 figs

MÖSSBAUER-BORRMANN SUPERRADIANCE

Considérons le comportement cinétique d'un laser pour produire des rayons gamma, construit de noyaux isomériques aux sites de réseau d'un cristal parfait et simple, dont les dimensions et la structure sont choisies pour favoriser l'émission anormale dans le mode de Borrmann qui contient le nombre maximum de reflexions de Bragg. Ceci réduit fortement l'excitation requise pour le lasing. Notre analyse de plusieurs systèmes hypothétiques démontre que la superradiance, plutôt que l'amplification d'émission spontanée, sera le mode d'opération, pour autant que les noyaux isomériques soient pompés très rapidement à un niveau Mossbauer de durée courte et que l'intégrité du cristal soit préservée. Ce résultat justifie la recherche de solution aux problèmes principaux : noyaux candidats, préparation de l'isomère, et transfert du niveau isomérique au niveau lasant.We consider the kinetic behavior of a gamma-ray laser comprising an array of isomeric nuclei located at regular lattice sites in a perfect single crystal of dimensions and structure so chosen as to favor anomalous emission into that Borrmann mode having the maximum possible number of component Bragg-reflected beams, which greatly reduces the excitation requirements. Our analysis of several hypothetical systems shows that superradiance, rather than amplified spontaneous emission, will then be the preferred mode of deexcitation, provided the nuclei can be pumped rapidly to a short-lived Mossbauer level while preserving crystal integrity. This warrants a search for solutions to the major problems : candidate nuclides. preparation of a storage isomer, and interlevel transfer from storage to lasing state

A computer-controlled automated test system for fatigue and fracture testing

A computer-controlled system consisting of a servohydraulic test machine, an in-house designed test controller, and a desktop computer has been developed for performing automated fracture toughness and fatigue crack growth testing both in the laboratory and in hot cells for remote testing of irradiated specimens. Both unloading compliance and dc-potential drop can be used to monitor crack growth. The test controller includes a dc-current supply programmer, a function generator for driving the servohydraulic test machine to required test outputs, five measurement channels (each consisting of low-pass filter, track/hold amplifier, and 16-bit analog-to-digital converter), and digital logic for various control and data multiplexing functions. The test controller connects to the computer via a 16-bit wide photo-isolated bidirectional bus. The computer, a Hewlett-Packard series 200/300, inputs specimen and test parameters from the operator, configures the test controller, stores test data from the test controller in memory, does preliminary analysis during the test, and records sensor calibrations, specimen and test parameters, and test data on flexible diskette for later recall and analysis with measured initial and final crack length information. During the test, the operator can change test parameters as necessary. 24 refs., 6 figs

The role of religion in decision-making on antenatal screening of congenital anomalies: A qualitative study amongst Muslim Turkish origin immigrants

Objective: to explore what role religious beliefs of pregnant Muslim women play in their decision-making on antenatal screening, particularly regarding congenital abnormalities and termination, and whether their interpretations of the religious doctrines correspond to the main sources of Islam. Design: qualitative pilot study using in-depth interviews with pregnant Muslim women. Setting: one midwifery practice in a medium-sized city near Amsterdam participated in the study. Participants: 10 pregnant Muslim women of Turkish origin who live in a high density immigrant area and who attended primary midwives for antenatal care were included in the study. Data collection and data analysis: to explore the role of religion in decision-making on antenatal screening tests, a topic list was constructed, including four subjects: being a (practising) Muslim, the view on unborn life, the view on disabled life and the view on termination. To analyse the interviews, open and axial coding based on the Grounded Theory was used and descriptive and analytical themes were identified and interpreted. Findings: all 10 interviewees stated that their faith played a role in their decision-making on antenatal screening, specific to the combined test. They did not consider congenital anomalies as a problem and did not consider termination to be an option in case of a disabled fetus. However, the Islamic jurisprudence considers that termination is allowed if the fetus has serious abnormalities, but only before 19 weeks plus one day of gestation. Key conclusions: religious convictions play a role regarding antenatal screening in pregnant Muslim women of Turkish origin. The interviewees did not consider a termination in case of an affected child. Women were unaware that within Islamic tradition there is the possibility of termination if a fetus has serious anomalies. Incomplete knowledge of religious doctrines may be influencing both decisions of antenatal screening and diagnostic tests uptake and of terminating a pregnancy for fetuses with serious anomalies. Implications for practise: counsellors should be aware of the role of religious beliefs in the decision-making process on antenatal screening tests. © 2013 The Authors