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 hospitalization2–4 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

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

Simulation and analysis of a TET-walker robot motion

Due to copyright restrictions, the access to the full text of this article is only available via subscription.Tetrahedral walker robots are a group of reconfigurable robots which makes them adaptable for the full spectrum of activities in places that wheeled robots are inapplicable. In this paper, two different gaits for a single-TETwalker are introduced and the motion of the robot is then simulated. Modeling of the robot and simulation of its tumbling and walking gaits are performed within the ADAMS software. While the prismatic joints of the struts are gradually manipulated to make a walking gait, the motion in the tumbling gait is managed by changing the mass center and causing it to topple. Simulation results are used to improve the characteristics of the robot and to compare the performance of its motion in the gaits presented

Color vision deficiency

Color vision deficiency (CVD) is a defect of vision with disability to distinguish colors. Color vision deficiency can be divided into the two categories, congenital and acquired. Congenital color vision deficiency divided into anomalous trichromacy, dichromacy and monochromacy. The most common congenital CVD was deuteranomalous that mode of inheritance is X linked recessive occurring mostly in males. Acquired CVD can occur as a direct result of illness or any related medicine. Color perception changes in acquired CVD may be secondary to primary ocular disease, drug side effect, or serious systemic disease such as diabetes. Dystrophy of cone, types of maculopathy, crystalline lens changes associated with aging, diabetes, glaucoma, optic nerve diseases and traumatic brain injuries can cause CVD. For acquired CVD, type of defect may not be easy to classify; nevertheless, predominantly is tritanopia and type and severity of the defect fluctuates during of disease. It has been suggested that human evolution to industrialized civilization has led to an increased prevalence of CVD in most population. An acquired CVD can reflect a deficiency in color information processing at anywhere along the related visual pathway, from the photoreceptors to the cortex. Sometimes, assessment of color vision can be helpful to detect a visual impairment in early stages

Pattern and Inclination of Adolescents Towards Substance Abuse

Introduction: Narcotic drug abuse and illicit use of drugs is a major, complicated multifactorial phenomenon affecting most of the societies today. Incidence of drug abuse among adolescents is very high. Adolescents become addicted to substances more quickly than adults. The aim of this study was to assess the pattern of drug abuse among male adolescents in Hamadan. Methods: This study was a descriptive study and samples (n=400) were collected on the basis of snowball sampling method. Information was collected individually through completion of a researcher-designed questionnaire including demographic and epidemiological indices, perceived familial support, religiosity, and locus of control. Results: The results showed that smoking (93%), alcohol (92.5%), marijuana (64.3%), and opium (57.8%) use were very high, while LSD (4.8%) and Cocaine(2.3%) use was rare. 77.8 % of adolescents began drug abuse between 12 and 18 years of age. Moreover, sensation seeking (26.5%), individual interest (24.8%), and peer pressure (22%), were the main reasons for drug abuse. Conclusion: As initial smoking, alcohol and marijuana use play an important role in determining the future addiction of adolescents to narcotics, yearly surveillance programs in the country and evaluation of etiological factors of narcotic addiction need to be studied carefully. All of the preventive and school programs designed for the young should take into account environmental, demographic and policy factors in addition to personal factors so that the programs have a maximum effect

Reason And Usage Of The Wise In Family Dispute Resolution Proceedings With The Implementation Of Judicial Decisions

In recent years, the use of reason has been the subject of much attention by legal writers and prosecutors. The use of this argument in the family law system has led to many ambiguities to the extent that the doctrine and the judiciary have not been adequately addressed. Therefore, as an essential part of the legal system and the proper quality of citing it as a judicial proof by the prosecutors, it is of great importance that the present article discusses the position of this argument and its analysis. Judiciary is based on an Osule feghh.En los últimos años, el uso de la razón ha sido objeto de mucha atención por parte de escritores legales y fiscales. El uso de este argumento en el sistema de derecho de familia ha generado muchas ambigüedades en la medida en que la doctrina y el poder judicial no se han abordado adecuadamente. Por lo tanto, como parte esencial del sistema legal y la calidad adecuada de citarlo como prueba judicial por parte de los fiscales, es de gran importancia que el presente artículo discuta la posición de este argumento y su análisis. El poder judicial se basa en un Osule feghh

Design and fabrication of a robotic tactile device for abdominal palpation

Due to copyright restrictions, the access to the full text of this article is only available via subscription.Palpation can be used as a manual technique for detecting normal and abnormal tissues. According to the recent applications of the robotic and control systems in medical fields, the design and fabrication of a device capable of abdominal palpation is of great importance. In this paper, a device has been designed and fabricated to be used for palpation examinations. A cable mechanism has been used to meet weight and size criteria of the device. The proposed design has been explained in detail. The device measures contact force between the probe and palpated tissue and also the deflection of the tissue as the probe is pressed against the body. Useful parameters of abdominal tissue such as stiffness can also be obtained.INS

Comparison of ISSR, IRAP and REMAP markers for assessing genetic diversity in different species of Brassica sp

Molecular markers provide facilities in order to study genetic diversity and relationship among genotypes. In this study, genetic diversity among 35 genotype of Brassica sp. (belonging B. napus, B. juncea, B. rapa, B. nigra) were determined using 13 ISSR, 3 IRAP markers and 18 REMAP (primer combinations of ISSR and retrotransposon primer). The percentage of polymorphism for ISSR, IRAP and REMAP was 96.38, 94 and 96%, respectively. By comparison between markers, ISSRs indicated the highest expected heterozygosity (H-e) and Shannon's information index (I) with value of 0.34 and 0.51, respectively, while REMAP marker had by far the highest number of polymorphic bands (340) and marker index (7.1) among all fragments scored over all markers. In pattern of clustering based on Bayesian methods, K = 8 was resulted for combined data clustering that was more organized clustering for genotypes compared to others. This research suggests the combined data of ISSR, IRAP and REMAP markers are most reliable than each solely marker whilst have been clustered genotypes in their taxonomic classification of Brassica without any mixture. Principle coordinate analysis (PCoA) separated 35 genotypes in four groups which all of genotypes were clustered correctly based on their taxonomic classification. The findings of this study provide the valuable insight into the Brassica species relationships in terms of similarity among genotypes which can be helpful in breeding programs, and also demonstrate that retrotransposon markers are legible for genetic diversity and next genetic analysis in Brassica genus