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

Exposure of surgeons-in-training to radiation during intramedullary fixation of femoral shaft fractures

ArticleThe original publication is available at http://www.samj.org.zaOwing to the continuous turnover of registrars and radiographers, most of the trauma-related orthopaedic surgery in this academic hospital is done by inexperienced surgeons-in-training and the fluoroscopy by junior radiographers. This could result in excessive radiation doses. Calibrated lithium fluoride thermoluminescent chips were secured to various parts of the primary surgeon's body to quantify the radiation dose received during the insertion of an intramedullary nail. Closed intramedullary fixation of 15 fractures of the femur was done with interlocking as necessary. The total average exposure time was 14 minutes 45 seconds per procedure. Distal locking took up 31% of this time. The mean radiation dose to the surgeon's eyes and thyroid was 0,13 mCy and to the dominant hand 2,10 mCy. This would allow the performance of about 350 such procedures per year before the maximum permissible dose level was reached. Recommendations to decrease irradiation dosage are made.Publisher’s versio

The Significance of Prelabour Type 11 .Deceleration of Fetal Heart Rate in Relation to Braxton-Hicks Contractions

During prelabour cardiotocography on 450 high risk antenatal patients, painless uterine contractions (BraxtonHicks) were recorded in 4 patients, who also showed a type 11 deceleration pattern. Two fetuses died and 2 were saved. In the 2 who died there was a delay of more than 12 hours between first observation and delivery, while in the 2 who were saved, immediate Caesarean section was performed. It is suggested that the sign of late deceleration in relation to Braxton-Hicks contractions is a preterminal manifestation of acute-on-chronic fetal distress, and the appropriate management should be immediate Caesarean section, whatever the gestation. Antenatal cardiotocography might therefore have a place in the assessment of the 'very small for gestational age fetus and an irritable uterus. This approach could ensure survival but not necessarily quality

African water storage pots for the delivery of the Entomopathogenic fungus Metarhizium anisopliae to the Malaria vectors Anopheles gambiae s.s. and Anopheles funestus

We studied the use of African water storage pots for point source application of Metarhizium anisopliae against the malaria vectors Anopheles gambiae s.s. and An. funestus. Clay pots were shown to be attractive resting sites for male and female An. gambiae s.s. and were not repellent after impregnation with fungus. M. anisopliae was highly infective and virulent after spray application inside pots. At a dosage of 4 x 1010 conidia/m2, an average of 95 ± 1.2% of An. gambiae s.s. obtained a fungal infection. A lower dosage of 1 x 1010 conidia/m2 infected an average of 91.5 ± 0.6% of An. gambiae s.s. and 91.8 ± 1.2% of An. funestus mosquitoes. Fungal infection significantly reduced mosquito longevity, as shown by differences between survival curves and LT50 values. These pots are suitable for application of entomopathogenic fungi against malaria vectors and their potential for sustainable field implementation is discussed

Dynamic simulation of the carbon-in-pulp and carbon-in-leach processes

Carbon-in-leach and carbon-in-pulp are continuous processes that use activated carbon in a cascade of large agitated tanks, which have been widely used to recover or concentrate precious metals in gold extraction plants. In the carbon-in-pulp process adsorption occurs after the leaching cascade section of the plant, and in the carbon-in-leach process leaching and adsorption occur simultaneously. In both processes the activated carbon is moved from one tank to another in countercurrent with the ore pulp until the recovery of the loaded carbon in the first tank. This paper presents a dynamic model that describes, with minor changes, the carbon-in-leach, the carbon-in-pulp, and the gold leaching processes. The model is numerically solved and calibrated with experimental data from a plant and used to perform a study of the effect of the activated carbon transfer strategy on the performance of the adsorption section of the plant. Based on the calculated values of the gold loss in the liquid and of the gold recovered in the loaded activated carbon that leaves the circuit, the results indicate that strategies in which a significant amount of activated carbon is held in the first tank and the contact time between the carbon and the pulp is longer are the best carbon transfer strategies for these processes