Some reactions of sulphonylhydroxylamines leading to an investigation of sulphonylaminyloxides

Mercury (II) and lead (II) ions, but not mercury (l) and thallium (I), react with both the nitrosyIdisulphonate, ON(S0₃)₂₂- and the hydroxylaminedisulphonate dianions, ON(S0₃)₂²⁻-, to yield the corresponding metal sulphate and a mixture of sulphate and sulphite ions. Silver (I) ions are reduced to the metal by both anions, but reacts with potassium imidodisulphonate, HN(SO₃K)₂, and tripotassium imidodisulphonate, KN(S0₃K)₂, to yield trisilver imidodisulphonate, Ag₃NS₂O₆, and disilver potassium imidodisulphonate, Ag₂KNS₂O₆. The reaction of some related salts are also reported. Mechanisms for some of the decompositions, and stoichiometric equations are proposed. No metal salts of hydroxylaminedisulphonates, HON(SO₃M)₂ were isolated. The silver imidodisulphonate salts failed to react with both alkyl and aryl halides. A series of N, N-bis-(arylsulphonyl)hydroxylamines, (p-XC₆H₄S₂)₂N0, were synthesised (X = H, Me, MeO, Cl and F). The species (p-XC₆H₄S₂)₂N0, p-XC₆H₄S₂NO and p-XC₆H₄S₂ are proposed as intermediates during the oxidation of the bis-species with PbO₂, silver (I,III) oxide, AgO, MnO₂. Pb(O₂CMe)₄ or nitric acid to N, N, 0-tris-(arylsulphonyl)hydroxylamines, p-XC₆H₄S₂)₂N0S₂C₆H₄X-p and nitrate ion. A mechanism involving hydroxylamine is ruled out. I. r. and n.m.r. spectra show that the tris-species are hydroxylamines, R₂NOR, rather than amine oxides, R₃NO, and the structure is considered by a comparison with (CF208)₂NOH and (CF₃)₂NO. The e.s.r. spectra of the tris-species in benzene indicates the presence of a nitroxide radical. The bis-species are found to decompose to the tris-hydroxylamine and the corresponding arenesulphonic acid, while the tris-species decompose to the sulphonic acid. Oligomerisation of cyclohexene is observed during the oxidation of bis-hydroxylamines, while with bases, such as pyridine, the hydroxylamine is converted to a mixture of (RSO₂)₂NH pyridine-N-oxide and a pyridinium arylsulphonate. N, N, 0-tris-(Alkyl-sulphonyl) hydroxylamines could not be isolated. Nitrosylarene-sulphinates, p-XC₆H₄SO₂NO are proposed as intermediates but could not be isolated from the reactions of nitrosyl chloride and nitrogen (II) oxide with arylsulphonylhydroxylamines. p-XC₆H₄SO₂NHOH, (p-XC₆H₄SO₂)₂NOH and p-XC₆H₄SO₂NH₂ (X=H, CH₃) are all are converted by NOCl to p-XC₆H₄SO₂Cl, but (p-XC₆H₄S0₂)₂N0S0₂C₆H₄X-p and (p-XC₆H₄SO₂)₂NH are unaffected. Oxidation of C₆H₅SO₂NHOH by a range of oxidants yielded, C₆H₅SO₂Cl, C₆H₅SO₃H, or (C₆H₅SO₂)₂NOSO₂C₆H₅, but not C₆H₅SO₂NO. Diene cycloaddition products of p-XC₆H₄SO₂NO could not be isolated. p-CH₃C₆H₄SO₂Na is converted by nitrosyl chloride to p-CH₃C₆H₄SO₂Cl rather than to p-CH₃C₆H₄SO₂NO. (p-CH₃C₆H₄SO₂)₂NH is inert to a wide range of oxidants. Both (p-XC₆H₄S0₂)₂NOH and (p-XC₆H₄S0₂)₂N0S0₂C₆H₄X-p initiate free-radical halogenation by dichlorine and dibromine, but not by diiodine, of benzene and cyclohexane. Simple carboxyamides also initiate free-radical chlorination of the same substrates. (N-aryl-N-arylsulphonyl) hydroxylamines were oxidised by PbO₂ and Pb(0₂CMe)₄, but not MnO₂, to a mixture of the corresponding [N- aryl-N, O -bis(aryl sulphonyl)]hydroxylamine, nitrobenzene and azoxybenzene. The tris-species appears to contain the nitroxide radical, ArS0₂N(0)Ar¹. A similar mechanism to that for the oxidation of (p-XC₆H₄S0₂)₂N0H is proposed

Disease activity and cognition in rheumatoid arthritis : an open label pilot study

Acknowledgements This work was supported in part by NIHR Newcastle Biomedical Research Centre. Funding for this study was provided by Abbott Laboratories. Abbott Laboratories were not involved in study design; in the collection, analysis and interpretation of data; or in the writing of the report.Peer reviewedPublisher PD

A model for reactive porous transport during re-wetting of hardened concrete

A mathematical model is developed that captures the transport of liquid water in hardened concrete, as well as the chemical reactions that occur between the imbibed water and the residual calcium silicate compounds residing in the porous concrete matrix. The main hypothesis in this model is that the reaction product -- calcium silicate hydrate gel -- clogs the pores within the concrete thereby hindering water transport. Numerical simulations are employed to determine the sensitivity of the model solution to changes in various physical parameters, and compare to experimental results available in the literature.Comment: 30 page

Retail innovation and shopping practices: consumers' reaction to self-service retailing

Authors' draft also available on Surrey eprints repository at http://epubs.surrey.ac.uk. Final version available online at http://www.envplan.com/In this paper we address the related issues of retail innovation, changing shopping practices, and shopping geographies. We do so in relation to the spread of self-service grocery stores, and particularly the supermarket, in the postwar retail environment of Britain (1950 – 70), arguing that this juncture provides a propitious opportunity to study the relationship between changing practices of retailing and consumption. We highlight shoppers’ selective adoption of new self-service formats in relation to certain product categories and argue that this can be explained in part by reference to the socially embedded nature of women food shoppers’ behaviours and in particular the influence of contemporary notions of the ‘good housewife’. We support our argument by reference to a wide range of contemporary documentary material relating to postwar shopping including market research reports, the publications of local consumer groups, and selected retailer and government archive sources

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

The SAMI Galaxy Survey: Cubism and covariance, putting round pegs into square holes

We present a methodology for the regularization and combination of sparse sampled and irregularly gridded observations from fibre-optic multiobject integral field spectroscopy. The approach minimizes interpolation and retains image resolution on combining subpixel dithered data. We discuss the methodology in the context of the Sydney-AAO multiobject integral field spectrograph (SAMI) Galaxy Survey underway at the Anglo-Australian Telescope. The SAMI instrument uses 13 fibre bundles to perform high-multiplex integral field spectroscopy across a 1° diameter field of view. The SAMI Galaxy Survey is targeting ~3000 galaxies drawn from the full range of galaxy environments. We demonstrate the subcritical sampling of the seeing and incomplete fill factor for the integral field bundles results in only a 10 per cent degradation in the final image resolution recovered. We also implement a new methodology for tracking covariance between elements of the resulting data cubes which retains 90 per cent of the covariance information while incurring only a modest increase in the survey data volume

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 hospitalization2–4 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

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

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