An MDA approach towards integrating formal and informal modeling languages

This paper shows how formal and informal modeling languages can be cooperatively used in the MDA framework, and how transformations between models in these languages can be achieved using an MDA development environment. The integrated approach also provides an effective V&V technique for the MDA

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

The assessment of local response using magnetic resonance imaging at 3- and 6-month post chemoradiotherapy in patients with anal cancer

OBJECTIVES: To assess the use of MRI-determined tumour regression grading (TRG) in local response assessment and detection of salvageable early local relapse after chemoradiotherapy (CRT) in patients with anal squamous cell carcinoma (ASCC). METHODS: From a prospective database of patients with ASCC managed through a centralised multidisciplinary team, 74 patients who completed routine post-CRT 3- and 6-month MRIs (2009–2012) were reviewed. Two radiologists blinded to the outcomes consensus read and retrospectively assigned TRG scores [1 (complete response) to 5 (no response)] and related these to early local relapse (within 12 months) and disease-free survival (DFS). RESULTS: Seven patients had early local relapse. TRG 1/2 scores at 3 and 6 months had a 100 % negative predictive value; TRG 4/5 scores at 6 months had a 100 % positive predictive value. All seven patients underwent salvage R0 resections. We identified a novel ‘tram-track’ sign on MRI in over half of patients, with an NPV for early local relapse of 83 % at 6 months. No imaging characteristic or TRG score independently prognosticated for late relapse or 3-year DFS. CONCLUSIONS: Post-CRT 3- and 6-month MRI-determined TRG scores predicted salvageable R0 early local relapses in patients with ASCC, challenging current clinical guidelines. KEY POINTS: • Post-chemoradiotherapy MRI (3 and 6 months) helps local response assessment in ASCC. • The MRI-TRG system can be used reproducibly in patients with ASCC. • The TRG system facilitates patient selection for examination under anaesthesia and biopsy. • The use of MRI-TRG predicts for detection of salvageable early local relapses. • The TRG system allows for a standardised follow-up pathway. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00330-016-4337-z) contains supplementary material, which is available to authorized users

Race, Multiculturalism and the ‘Progressive’ Politics of London 2012: Passing the ‘Boyle Test’

This paper will examine the ways in which race, multiculturalism and nation have been constructed, used and evoked in the London 2012 Olympics bid, branding and promotion. The paper will focus on the two-pronged strategy promoting modern, diverse, multicultural Britain and the more conservative traditional, historic Britain, and the tensions and contradictions between these. These are tensions and contradictions which have been exposed and exacerbated by 7/7, recession and riots, as well as the shift in government from New Labour to the Tory-led coalition. The paper will examine the ways in which race and nation have played a role historically and politically in the Olympics, and then examine the place and use of race in three aspects of the 2012 Games: the bid and branding, the opening ceremony and the representation of the athletes themselves. The paper will argue that far from being progressive and inclusive as has been promoted and claimed, what has occurred around London 2012 has been a conservative hegemonic re-articulation of a 'Britishness' that is 'progressive' and includes immigrants and black and minority ethnic individuals based on a logic of integration and performance that does not threaten, criticise or make demands of more traditional visions of Britishness. Moreover, athletes such as Mo Farah have been positioned in such a way as to challenge racism and xenophobia and re-brand Britain as inclusive in narrow terms and at the same time serve as aspirational individual role models through which to set expectations for and make demands of immigrant, black and minority ethnic youth and wider communities