Shape optimisation of the sharp-heeled Kaplan draft tube: Performance evaluation using Computational Fluid Dynamics

A methodology to assess the performance of an elbow-type draft tube is outlined. This was achieved using Computational Fluid Dynamics (CFD) to evaluate the pressure recovery and mechanical energylosses along a draft tube design, while using open-source and commercial software to parameterise and regenerate the geometry and CFD grid. An initial validation study of the elbow-type draft tube is carriedout, focusing on the grid-regeneration methodology, steady-state assumption, and turbulence modelling approach for evaluating the design’s efficiency. The Grid Convergence Index (GCI) technique was used to assess the uncertainty of the pressure recovery to the grid resolution. It was found that estimating the pressure recovery through area-weighted averaging significantly reduced the uncertainty due to the grid. Simultaneously, it was found that this uncertainty fluctuated with the local cross-sectional area along the geometry. Subsequently, a study of the inflow cone and outer-heel designs on the flowfield and pressure recovery was carried out. Catmull-Rom splines were used to parameterise these components, so as torecreate a number of proposed designs from the literature. GCI analysis is also applied to these designs,demonstrating the robustness of the grid-regeneration methodology

Observation of hard scattering in photoproduction events with a large rapidity gap at HERA

Events with a large rapidity gap and total transverse energy greater than 5 GeV have been observed in quasi-real photoproduction at HERA with the ZEUS detector. The distribution of these events as a function of the $\gamma p$ centre of mass energy is consistent with diffractive scattering. For total transverse energies above 12 GeV, the hadronic final states show predominantly a two-jet structure with each jet having a transverse energy greater than 4 GeV. For the two-jet events, little energy flow is found outside the jets. This observation is consistent with the hard scattering of a quasi-real photon with a colourless object in the proton.Comment: 19 pages, latex, 4 figures appended as uuencoded fil

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

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

The effect of the Halothane gene on performance, carcass and meat quality in a fat and a lean line of pigs

The performance, carcass and meat quality of two lines of pigs in which the halothane allele (n) was segregating were studied. The lines were a lean line selected for rapid lean growth and an unselected fat line. Heterozygous (Nn) and homozygous normal (NN) segregants in both lines were compared in an environment of high temperature and pre-slaughter transport stress. Relative to the fat line, the lean line grew faster, ate more, was a more efficient converter of food and produced leaner carcasses. It also produced less acid and darker lean with less water loss. The halothane allele had a much greater effect in the lean than the fat line. It reduced appetite, growth rate and food conversion ratio and increased the acidity, paleness and water loss from lean. In both lines, but particularly in the lean line, the halothane allele increased the incidence of death in transit to slaughter

The effect of the Halothane gene on performance, carcass and meat quality in a fat and a lean line of pigs

The performance, carcass and meat quality of two lines of pigs in which the halothane allele (n) was segregating were studied. The lines were a lean line selected for rapid lean growth and an unselected fat line. Heterozygous (Nn) and homozygous normal (NN) segregants in both lines were compared in an environment of high temperature and pre-slaughter transport stress. Relative to the fat line, the lean line grew faster, ate more, was a more efficient converter of food and produced leaner carcasses. It also produced less acid and darker lean with less water loss. The halothane allele had a much greater effect in the lean than the fat line. It reduced appetite, growth rate and food conversion ratio and increased the acidity, paleness and water loss from lean. In both lines, but particularly in the lean line, the halothane allele increased the incidence of death in transit to slaughter

4,10-Diallyloxy-1,2,3,6b,7,8,9,12b-octahydroperylene

In the title compound, C(26)H(28)O(2), the central atoms are coplanar, with the -CH(2)-CH(2)- links of the cyclohexene groups lying to either side of the plane and with the diallyloxy residues twisted out of this plane [C-C-O-C torsion angles = 16.6 (3) and -13.9 (3)degrees]. In the crystal structure, molecules are connected into chains propagating in [100] via C-H center dot center dot center dot pi interactions