Numerical study of the noninertial systems: applicationto train coupler systems

Car coupler forces have a significant effect on the longitudinal train dynamics and stability. Because the coupler inertia is relatively small in comparison with the car inertia; the high stiffness associated with the coupler components can lead to high frequencies that adversely impact the computational efficiency of train models. The objective of this investigation is to study the effect of the coupler inertia on the train dynamics and on the computational efficiency as measured by the simulation time. To this end, two different models are developed for the car couplers; one model, called the inertial coupler model, includes the effect of the coupler inertia, while in the other model, called the noninertial model, the effect of the coupler inertia is neglected. Both inertial and noninertial coupler models used in this investigation are assumed to have the same coupler kinematic degrees of freedom that capture geometric nonlinearities and allow for the relative translation of the draft gears and end of car cushioning (EOC) devices as well as the relative rotation of the coupler shank. In both models, the coupler kinematic equations are expressed in terms of the car body and coupler coordinates. Both the inertial and noninertial models used in this study lead to a system of differential and algebraic equations that are solved simultaneously in order to determine the coordinates of the cars and couplers. In the case of the inertial model, the coupler kinematics is described using the absolute Cartesian coordinates, and the algebraic equations describe the kinematic constraints imposed on the motion of the system. In this case of the inertial model, the constraint equations are satisfied at the position, velocity, and acceleration levels. In the case of the noninertial model, the equations of motion are developed using the relative joint coordinates, thereby eliminating systematically the algebraic equations that represent the kinematic constraints. A quasistatic force analysis is used to determine a set of coupler nonlinear force algebraic equations for a given car configuration. These nonlinear force algebraic equations are solved iteratively to determine the coupler noninertial coordinates which enter into the formulation of the equations of motion of the train cars. The results obtained in this study showed that the neglect of the coupler inertia eliminates high frequency oscillations that can negatively impact the computational efficiency. The effect of these high frequencies that are attributed to the coupler inertia on the simulation time is examined using frequency and eigenvalue analyses. While the neglect of the coupler inertia leads, as demonstrated in this investigation, to a much more efficient model, the results obtained using the inertial and noninertial coupler models show good agreement, demonstrating that the coupler inertia can be neglected without having an adverse effect on the accuracy of the solutio

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