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

Knowledge in the loop: Semantics representation for multimodal simulative environments

Latoschik ME, Biermann P, Wachsmuth I. Knowledge in the loop: Semantics representation for multimodal simulative environments. In: Butz A, Fisher B, Krüger A, Olivier P, eds. Smart Graphics. LNCS 3638. Berlin: Springer; 2005: 25-39.This article describes the integration of knowledge based techniques into simulative Virtual Reality (VR) applications. The approach is motivated using multimodal Virtual Construction as an example domain. An abstract Knowledge Representation Layer (KRL) is proposed which is expressive enough to define all necessary data for diverse simulation tasks and which additionally provides a base formalism for the integration of Artificial Intelligence (AI) representations. The KRL supports two different implementation methods. The first method uses XSLT processing to transform the external KRL format into the representation formats of the diverse target systems. The second method implements the KRL using a functionally extendable semantic network. The semantic net library is tailored for real time simulation systems where it interconnects the required simulation modules and establishes access to the knowledge representations inside the simulation loop. The KRL promotes a novel object model for simulated objects called Semantic Entities which provides a uniform access to the KRL and which allows extensive system modularization. The KRL approach is demonstrated in two simulation areas. First, a generalized scene graph representation is presented which introduces an abstract definition and implementation of geometric node interrelations. It supports scene and application structures which can not be expressed using common scene hierarchies or field route concepts. Second, the KRL’s expressiveness is demonstrated in the design of multimodal interactions. Here, the KRL defines the knowledge particularly required during the semantic analysis of multimodal user utterances

Using Ontology to Establish Social Context and Support Social Reasoning

Abstract. Believable agents are required to express human-like characteristics. While most recent research focus on graphics and plan execution, few concen-trate on the issue of flexible interactions by reasoning about social relations. This paper integrates the idea of social constraints with social ontology to pro-vide a machine readable framework as a standard model which can support so-cial reasoning for generic BDI agents. A scenario is illustrated to show how so-cial reasoning can be attained even in different social context.

Social signal processing: the research agenda

The exploration of how we react to the world and interact with it and each other remains one of the greatest scientific challenges. Latest research trends in cognitive sciences argue that our common view of intelligence is too narrow, ignoring a crucial range of abilities that matter immensely for how people do in life. This range of abilities is called social intelligence and includes the ability to express and recognise social signals produced during social interactions like agreement, politeness, empathy, friendliness, conflict, etc., coupled with the ability to manage them in order to get along well with others while winning their cooperation. Social Signal Processing (SSP) is the new research domain that aims at understanding and modelling social interactions (human-science goals), and at providing computers with similar abilities in human–computer interaction scenarios (technological goals). SSP is in its infancy, and the journey towards artificial social intelligence and socially aware computing is still long. This research agenda is twofold, a discussion about how the field is understood by people who are currently active in it and a discussion about issues that the researchers in this formative field face