Control strategies for integration of electric motor assist and functional electrical stimulation in paraplegic cycling: Utility for exercise testing and mobile cycling

AIM: The aim of this study was to investigate feedback control strategies for integration of electric motor assist and functional electrical stimulation (FES) for paraplegic cycling, with particular focus on development of a testbed for exercise testing in FES cycling, in which both cycling cadence and workrate are simultaneously well controlled and contemporary physiological measures of exercise performance derived. A second aim was to investigate the possible benefits of the approach for mobile, recreational cycling. METHODS: A recumbent tricycle with an auxiliary electric motor is used, which is adapted for paraplegic users, and instrumented for stimulation control. We propose a novel integrated control strategy which simultaneously provides feedback control of leg power output (via automatic adjustment of stimulation intensity) and cycling cadence (via electric motor control). Both loops are designed using system identification and analytical (model-based) feedback design methods. Ventilatory and pulmonary gas exchange response profiles are derived using a portable system for real-time breath-by-breath acquisition. RESULTS:We provide indicative results from one paraplegic subject in which a series of feedback-control tests illustrate accurate control of cycling cadence, leg power control, and external disturbance rejection. We also provide physiological response profiles from a submaximal exercise step test and a maximal incremental exercise test, as facilitated by the control strategy. CONCLUSION: The integrated control strategy is effective in facilitating exercise testing under conditions of well-controlled cadence and power output. Our control approach significantly extends the achievable workrate range and enhances exercise-test sensitivity for FES cycling, thus allowing a more stringent characterization of physiological response profiles and estimation of key parameters of aerobic function.We further conclude that the control approach can significantly improve the overall performance of mobile recreational cycling

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

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

Effect of 2 weeks of sprint interval training on health-related outcomes in sedentary overweight/obese men

The aim of this study was to investigate the effects of very high intensity sprint interval training (SIT) on metabolic and vascular risk factors in overweight/obese sedentary men. Ten men (age, 32.1 ± 8.7 years; body mass index, 31.0 ± 3.7 kg m-2) participated. After baseline metabolic, anthropometric, and fitness measurements, participants completed a 2-week SIT intervention, comprising 6 sessions of 4 to 6 repeats of 30-second Wingate anaerobic sprints on an electromagnetically braked cycle ergometer, with 4.5-minute recovery between each repetition. Metabolic, anthropometric, and fitness assessments were repeated post-intervention. Both maximal oxygen uptake (2.98 ± 0.15 vs 3.23 ± 0.14 L min-1, P = .013) and mean Wingate power (579 ± 24 vs 600 ± 19 W, P = .040) significantly increased after 2 weeks of SIT. Insulin sensitivity index (5.35 ± 0.72 vs 4.34 ± 0.72, P = .027) and resting fat oxidation rate in the fasted state (0.13 ± 0.01 vs 0.11 ± 0.01 g min-1, P = .019) were significantly higher and systolic blood pressure (121 ± 3 vs 127 ± 3 mm Hg, P = .020) and resting carbohydrate oxidation in the fasted state (0.03 ± 0.01 vs 0.08 ± 0.02 g min-1, P = .037) were significantly lower 24 hours post-intervention compared with baseline, but these changes were no longer significant 72 hours post-intervention. Significant decreases in waist (98.9 ± 3.1 vs 101.3 ± 2.7 cm, P = .004) and hip (109.8 ± 2.2 vs 110.9 ± 2.2 cm, P = .017) circumferences compared with baseline were also observed after the intervention. Thus, 2 weeks of SIT substantially improved a number of metabolic and vascular risk factors in overweight/obese sedentary men, highlighting the potential for this to provide an alternative exercise model for the improvement of vascular and metabolic health in this population

Ventilatory control during intermittent high-intensity exercise in humans

Intermittent supra-maximal cycling of varying work: recovery durations was used to explore the kinetics of respiratory compensation for the metabolic acidosis of high-intensity exercise ( gt lactate threshold, theta(L)). For a 10:20s duty-cycle, blood [lactate] ([L-]) was not increased, and there was no evidence of respiratory compensation (RC); Le, no increase in the ventilation (V-E)-CO2 Output (V-CO2) slope, nor fall in end-tidal PCO2 (PETCO2). For longer duty-cycles, [L-] was elevated, stabilizing (30 s:60 s exercise) or rising progressively (60 s: 120 s, 90 s: 180 s exercise). In addition, V-CO2 and VE now oscillated with WR, with evidence of delayed RC (progressive increase in VE - V-CO2 slope; decrease in PETCO2) being more marked with longer duty-cycles. These results, which extend earlier findings with supra- theta(L) step and ramp exercise, are not consistent with an appreciable contribution to RC from zero-order central command or peripheral neurogenesis. The reasons for the slow RC kinetics are unclear, but may reflect in part the H+-signal transduction properties of carotid chemoreceptor

Workrate and cadence control for exercise testing in FES cycling

No abstract available

Paradoxes of participation : non-union workplace partnerships in John Lewis

The extent to which workplace partnership delivers mutual gains is subject to considerable debate amongst practitioners and scholars. One of the oldest and largest examples of workplace partnership is the John Lewis Partnership that began using forms of non-union employee representation in 1929. Despite ongoing interest from researchers in employee representation, and specifically non-union forms of employee voice, there have been few in-depth studies of the Partnership's organisational structure and practices since the 1980s. This paper explores in detail the operation of representation structures in the John Lewis Partnership, which is a significant case of non-union workplace partnership with the potential for mutual gains. A key finding of the paper was that the decision-making structures that characterise the Partnership, and that are protected by a constitution, are under constant threat from the discursive struggle to define partnership in a way that privileges managerial interests. The paper argues, therefore, that mutual gains need to be secured both structurally and discursively to address the tensions and paradoxes at the heart of debates about the meaning and aims of employee representation.\ud \u